PK OJHrefs.MYD^ ?J2012Vinyl chloride451-478AIARC Monographs on the Evaluation of Carcinogenic Risks to Humans100FDASSESSMENT CARCINOGENICITY RISK RISK ASSESSMENT VINYL VINYL CHLORIDE20121209281 Not in File ?2017>Childhood cancer treatment can affect psychosexual development17Nursing Standard3126}ADULT Affect ANTINEOPLASTIC DRUGS CANCER childhood CHILDREN Development DEVELOPMENTAL DRUG drugs RESEARCH toxic TREATMENT WHO 2/22/2017121080) field[33]: Not in File ?20172E-cigarettes are less toxic and safer than smoking16Nursing Standard3126pCIGARETTE Cigarettes E CIGARETTE E Cigarettes E-CIGARETTE e-Cigarettes e-liquid NICOTINE SMOKING STUDY toxic use 2/22/2017121081) field[33]: Not in File ?2017 Spironolactone-potion or poison?13Drug and Therapeutics Bulletin552Poison SPIRONOLACTONE2/2/2017120706) field[33]: Not in Fileb?2017The UK pesticide guide 2017 WallingfordCABI PublishingWFORENSIC FORESTRY INFORMATION pesticide PESTICIDES Regulation REGULATIONS Source UK WHO2017Edited by a leading authority in the field, this new edition of "The UK Pesticide Guide" has been thoroughly updated with new regulations which make "The UK Pesticide Guide" the most up-to-date information available for the main spraying season. "The UK Pesticide Guide" is the authoritative source of information on pesticides and adjuvants for UK agriculture, horticulture, forestry and amenity use. The book is produced by an independent editor and published by two independently funded, not-for profit organisations. This is the one essential handbook for advisors, contractors, farmers, sprayer operators, professional ground-keepers, local government and everyone who works with pesticides.120841Lainsbury, M.A.1-743 Not in File?#Abel, M.L. Kokosis, G. Blazer, D.G.2017cPulmonary toxicity after intraperitoneal mitomycin C: a case report of a rare complication of HIPEC49"World Journal of Surgical Oncology151ABSORPTION case CASE REPORT Case-report chemotherapeutics CHEMOTHERAPY drug-induced INTRAPERITONEAL Knowledge LEAD MITOMYCIN C NEOPLASM NEUTROPENIA PULMONARY PULMONARY TOXICITY SURGERY SYSTEMIC Toxicities TOXICITY TREATMENT 2/20/2017BACKGROUND: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has become a common treatment approach for disseminated appendiceal neoplasms. Systemic absorption of intraperitoneal chemotherapeutics may lead to drug-induced toxicity, most commonly neutropenia. Mitomycin C has been the most commonly used chemotherapeutic in HIPEC for the past several decades. CASE PRESENTATION: Here, we describe a rare pulmonary complication secondary to intraperitoneal administration of mitomycin C. CONCLUSIONS: While rare, intraperitoneal mitomycin C has the potential to cause serious pulmonary toxicity that should be considered with administration. To our knowledge, this report represents only the second case described in the literature121145+ field[33]: Not in File B?Abouchedid, R. Hudson, S. Thurtle, N. Yamamoto, T. Ho, J.H. Bailey, G. Wood, M. Sadones, N. Stove, C.P. Dines, A. Archer, J.R.H. Wood, D.M. Dargan, P.I.2017Analytical confirmation of synthetic cannabinoids in a cohort of 179 presentations with acute recreational drug toxicity to an Emergency Department in London, UK in the first half of 2015Clinical Toxicology0online early: doi: 10.1080/15563650.2017.1287373not published, 03 Mar 175F-AKB-48 5F-PB-22 AB-CHMINACA ACUTE ADULT Agitation AKB48 ANALYTICAL As CANNABINOID cannabinoids CANNABIS CLINICAL Cohort Cohort studies Cohort study Confirmation DATA DRUG drug toxicity drugs Emergencies emergency EMERGENCY DEPARTMENT HOSPITAL Liquid chromatography MASS SPECTROMETRY MDMB CHMICA MDMB-CHMICA new psychoactive substance NEW PSYCHOACTIVE SUBSTANCES NOVEL PSYCHOACTIVE SUBSTANCES PATIENT PB-22 seizure SEIZURES SERUM STUDY SYNTHETIC CANNABINOID Synthetic cannabinoids Toxicities TOXICITY UK use 2/20/2017Context: Synthetic cannabinoid receptor agonists are the largest group of new psychoactive substances reported in the last decade; in this study we investigated how commonly these drugs are found in patients presenting to the Emergency Department with acute recreational drug toxicity.Methods: We conducted an observational cohort study enrolling consecutive adult patients presenting to an Emergency Department (ED) in London (UK) January-July 2015 (6 months) with acute recreational drug toxicity. Residual serum obtained from a serum sample taken as part of routine clinical care was analyzed using high-resolution accurate mass-spectrometry with liquid-chromatography (HRAM-LCMSMS). Minimum clinical data were obtained from ED medical records.Results: 18 (10%) of the 179 patient samples were positive for synthetic cannabinoid receptor agonists. The most common was 5F AKB-48 (13 samples, concentration 50-7600 pg/ml), followed by 5F PB-22 (7, 30-400 pg/mL), MDMB-CHMICA (7, 80-8000 pg/mL), AB-CHMINACA (3, 50–1800 pg/mL), Cumyl 5F-PINACA (1, 800 pg/mL) and BB-22 (1, 60 pg/mL). Only 9/18 (50%) in whom synthetic cannabinoid receptor agonists were detected self-reported synthetic cannabinoid receptor agonist use. The most common clinical features were seizures and agitation, both recorded in four (22%) individuals. Fourteen patients (78%) were discharged from the ED, one of the four admitted to hospital was admitted to critical care.Conclusions: Synthetic cannabinoid receptor agonists were found in 10% of this cohort with acute recreational drug toxicity but self-reported in only half of these. This suggests that presentations to the ED with acute synthetic cannabinoid receptor agonist toxicity may be more common than reported121155/ field[33]: Not in FileB?Adkins, A.E. Hack, L.M. Bigdeli, T.B. Williamson, V.S. McMichael, G.O. Mamdani, M. Edwards, A. Aliev, F. Chan, R.F. Bhandari, P. Raabe, R.C. Alaimo, J.T. Blackwell, G.G. Moscati, A.A. Poland, R.S. Rood, B. Patterson, D.G. Walsh, D. Whitfield, J.B. Zhu, G. Montgomery, G.W. Henders, A.K. Martin, N.G. Heath, A.C. Madden, P.A. Frank, J. Ridinger, M. Wodarz, N. Soyka, M. Zill, P. Ising, M. Nöthen, M.M. Kiefer, F. Rietschel, M. Gelernter, J. Sherva, R. Koesterer, R. Almasy, L. Zhao, H. Kranzler, H.R. Farrer, L.A. Maher, B.S. Prescott, C.A. Dick, D.M. Bacanu, S.A. Mathies, L.D. Davies, A.G. Vladimirov, V.I. Grotewiel, M. Bowers, M.S. Bettinger, J.C. Webb, B.T. Miles, M.F. Kendler, K.S. Riley, B.P.2017~Genomewide association study of alcohol dependence identifies risk loci altering ethanol-response behaviors in model organisms.Alcoholism, Clinical and Experimental Research%online early: doi: 10.1111/acer.13362not published, 01 Mar 17vACUTE ALCOHOL Alcohol dependence ANTAGONIST Association Behavior behaviors BRAIN brain function case Convulsion CONVULSIONS DANTROLENE dependence Development DOE ETHANOL evidence GENE EXPRESSION genetic HUMAN INJECTION IS Meta-analysis method methods MICE MODEL Motivation Population POST MORTEM Post-mortem POSTMORTEM RAT rats RISK Sensitivity signal STUDY TISSUE TOLERANCE 2/22/2017zBACKGROUND: Alcohol Dependence (AD) shows evidence for genetic liability, but genes influencing risk remain largely unidentified. METHODS: We conducted a genomewide association study in 706 related AD cases and 1748 unscreened population controls from Ireland. We sought replication in 15,496 samples of European descent. We used model organisms to assess the role of orthologous genes in ethanol response behaviors. We tested one primate-specific gene for expression differences in case/control post-mortem brain tissue. RESULTS: We detected significant association in COL6A3 and suggestive association in two previously implicated loci, KLF12 and RYR3. None of these signals are significant in replication. A suggestive signal in the long noncoding RNA LOC339975 is significant in case:control meta-analysis, but not in a population sample. Knockdown of a COL6A3 ortholog in C. elegans reduced ethanol sensitivity. Col6a3 expression correlated with handling-induced convulsions in mice. Loss of function of the KLF12 ortholog in C. elegans impaired development of acute functional tolerance. Klf12 expression correlated with locomotor activation following ethanol injection in mice. Loss of function of the RYR3 ortholog reduced ethanol sensitivity in C. elegans and rapid tolerance in Drosophila. The ryanodine receptor antagonist dantrolene reduced motivation to self-administer ethanol in rats. Expression of LOC339975 does not differ between cases and controls but is reduced in carriers of the associated rs11726136 allele in nucleus accumbens. CONCLUSIONS: We detect association between AD and COL6A3, KLF12, RYR3 and LOC339975. Despite non-replication of COL6A3, KLF12 and RYR3 signals, orthologs of these genes influence behavioral response to ethanol in model organisms, suggesting potential involvement in human ethanol response and AD liability. The associated LOC339975 allele may influence gene expression in human nucleus accumbens. Although the functions of long noncoding RNAs are poorly understood, there is mounting evidence implicating these genes in multiple brain functions and disorders This article is protected by copyright. All rights reserved120933$ field[33]: Not in File ? ,Akhgari, M. Mobaraki, H. Etemadi-Aleagha, A.2017VHistopathological study of cardiac lesions in methamphetamine poisoning-related deaths5Daru251_ABUSE ALCOHOL AMFETAMINE amphetamine analysis As ATHEROSCLEROSIS BILE BLOOD CARDIAC CARDIOTOXICITY CARDIOVASCULAR case CATECHOLAMINES CHROMATOGRAPHY Content DEATH Deaths DRUG drugs FAILURE FORENSIC Forensic Medicine GA GAS gas chromatography/mass spectrometry GASTRIC HAZARD HEALTH Health hazard health hazards HEART heart failure high performance liquid chromatography HYPERTROPHY IS LESIONS Liquid chromatography LIVER Medicine METHAMPHETAMINE Methamphetamine toxicity method methods MICROSCOPY Organs PATHOLOGY Poison POISONING Release SPECTROMETRY STUDY TISSUE Toxicities TOXICITY TOXICOLOGY TRIAL URINE 2/17/2017ZBACKGROUND: Methamphetamine abuse is a worldwide health concern. Methamphetamine causes health hazards in many vital organs. It can cause damage to cardiac tissue via catecholamines release. Methamphetamine related deaths are becoming one of the most important problems in Iran. The purpose of the present study was to determine cardiac pathology in methamphetamine poisoning-related deaths. METHODS: The study included 100 cases of methamphetamine poisoning-related deaths and 100 cases as control group. Toxicology analysis of liver, gastric content, bile, urine, blood and vitreous humor were conducted to detect drugs, poisons and alcohols using thin layer chromatography, gas chromatography/mass spectrometry, and high performance liquid chromatography. Positive toxicology analysis results except for amphetamine and methamphetamine were excluded from the study in order to omit interfering factors. The most striking features of cardiac damage were observed by light microscopy. RESULTS: Methamphetamine and amphetamine were detected in either urine or gastric content samples. In all of the cases methamphetamine toxicity was determined to be a direct cause of death by forensic medicine practitioner. Cardiovascular pathology was noted in 68% of studied cases. The most common histopathologic features were myocardial fiber hypertrophy, mild, moderate to severe atherosclerosis and focal degeneration/necrosis. CONCLUSION: The results of the present study indicate that cardiotoxicity is one of the major contributing factors in methamphetamine poisoning related deaths. Overall, the current study highlights the fact that cardiotoxic effects of methamphetamine can explain increasing reports of heart failure and consequently death in young abusers. TRIAL REGISTRATION: Not applicable. Histopathological study of cardiac lesions in methamphetamine poisoning-related deaths120976+ field[33]: Not in FileE? -Al-Amry, M.A. Al-Abdan, N. Al-Othaimeen, S.A.2017FToxic keratitis after use of wrongly labeled non-ophthalmic medication141-143Saudi Pharmaceutical Journal251ANTIBIOTIC DICLOFENAC edema Emergencies emergency errors EYE EYE DROPS eye-drops FEMALE INJECTION KERATITIS OCULAR PATIENT THERAPY TOPICAL toxic TRAUMA use1/2017We present a 24-year-old female with trauma to her right eye. The patient was prescribed topical Tobramicin-dexamethasone eye drops but the pharmacy dispensed diclofenac diethyl amine ointment. The patient presented to the emergency room with lid edema, conjunctival injection and a corneal epithelial defect and toxic keratitis. The patient was successfully managed with copious irrigation, bandage contact lens and topical antibiotic therapy121112, field[33]: Not in FileB? "Al-Hammad, B.A. Abd El-Salam, M.M.2017iMonitoring water pollution levels in Wadi Hanifa, Riyadh, Saudi Arabia and its public health implications6Bulletin of Environmental Contamination and Toxicology,online early: doi: 10.1007/s00128-017-2048-znot published, 01 Mar 17analysis As Cd chemical CONCENTRATIONS Consumption FISH HEALTH Heavy metal HUMAN LEVELS METALS method methods MONITORING MUSCLE POLLUTION PUBLIC PUBLIC HEALTH quality SAFETY standards STUDY TISSUE WATER 2/18/2017This study was performed to evaluate the levels of metals in the fish caught from Wadi Hanifa's main basin over four seasons, determine the potential fitness of the fish for human consumption, and evaluate the overall water quality after enforcement of local standards. The physical and chemical parameters from a total of 192 water samples were tested using standard methods. Additionally, a total of 48 fish samples were analyzed for heavy metal concentrations. Mean values for basic water quality parameters of COD, PO4-3, NH3--N, and NO3--N exceeded Saudi standards in all seasons. Mean metal concentrations in water were consistently at their highest concentrations in samples collected during the summer, and the lowest in samples collected during the winter. Mean metal concentrations in fish muscle tissue exceeded Saudi standards for As and Cd, and United Nations FAO standards for Cr, Ni, Zn, Fe and Mn. Statistical analysis showed highly significant positive correlations between metal concentrations in water and metal concentrations in fish muscle for As-Fe, Pb-Cr, Pb-Ni, Cr-Cu, and Cu-Fe. This study highlights the urgent need for monitoring and controlling wastewater discharge in Wadi Hanifa to ensure public safety120957+ field[33]: Not in File? Al-Mendalawi, M.D.20175Diffuse scalp hair loss due to levothyroxine overdose55-56!Indian Dermatology Online Journal81=ALBUMIN ALOPECIA As Association author BLOOD case CASE REPORT Case-report CELL CLINICAL deficiency DERMAL Development DISEASE ENZYME GROWTH HAIR Hand Homeostasis HORMONE hormones HUMAN INFANT IS LETTER LEVOTHYROXINE Occurrence OVERDOSE PATIENT PERIPHERAL PLASMA SERUM Serum Albumin signal THERAPY thyroid urinary ZINC1/2017121021- field[33]: Not in File B? ^Al-Mukhaini, N. Ba-Omar, T. Eltayeb, E. Al-Shihi, A. Al-Riyami, N. Al-Belushi, J. Al-Adawi, K.2017LLiver and kidney toxicity induced by Afzal smokeless tobacco product in OmanTissue and Cell-online early: doi: 10.1016/j.tice.2017.01.008not published, 01 Mar 17ADULT ALANINE ANIMAL Animals As BLOOD CREATININE dose DRINKING WATER EXPOSURE FIBROSIS Gender HEPATOTOXICITY IS KIDNEY LEVELS LIVER LIVER FUNCTION NEPHROTOXICITY NITROGEN Organs RAT rats RENAL TOBACCO Toxicities TOXICITY toxin TOXINS UREA WATER WEIGHT Wistar rat Wistar rats2/6/2017VAfzal, the common smokeless tobacco product (STP) in Oman, is believed to contain toxins that may impair the function of some organs such as liver and kidney. An aqueous extract from Afzal was added to drinking water to be administrated orally to Wistar albino rats (n=72) young and adult from both genders weighing between 60-80g and 150-240g respectively for 8 weeks. Animals were divided into three groups: control (distilled water instead of Afzal extract), low-dose (3mgnicotine/kgbodyweight/day) and high-dose (6mgnicotine/kgbodyweight/day). The animals were euthanized and their blood, liver and kidney were collected for biochemical and histopathological investigations. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were assayed for the liver function, while blood urea nitrogen (BUN) and creatinine (CRT) were assayed for the kidney function. The results showed a significant increase in the ALT, AST, BUN and CRT levels (P<0.05) in both Afzal-treated groups (low and high doses) compared with the control. Histopathological findings revealed the initial but seem to be serious degenerative alterations of periportal fibrosis in liver and edematous and calcified changes in renal glomerulus among Afzal-treated groups. Additionally, the weight gain of the Afzal-treated groups was lower than the control group. Our findings show that the exposure of Wistar rats to the Afzal extract has the potentials of causing decreased weight gain and dose-dependent functional and structural damage to the biochemical and histological profiles of liver and kidney as well as serious biochemical effects121121, field[33]: Not in File ?J,Alizadeh-Ghamsari, A. Dadpour, B. Najari, F.2015|Pathological findings of tramadol on liver tissue in the cadaver referred to legal medicine organization of Tehran 2008-201359-64AInternational Journal of Medical Toxicology and Forensic Medicine62ACUTE acute poisoning Age ALVEOLAR As ATELECTASIS AUTOPSY BLADDER BLOOD case CELL CHRONIC chronic pain COMPUTER Content DEATH edema FORENSIC Forensic Medicine history Incidence INFORMATION IS LEGAL LIVER Medicine men method methods OPIOID Organs pain PATIENT POISONING Side effect side effects side-effects SOFTWARE STOMACH STUDY SURGERY Synthetic Opioid TEST Testing TISSUE TOXICOLOGY TRAMADOL URINE US use WHO WOMEN2015Background: Tramadol is a synthetic opioid used to control chronic pain and pain after surgery. However, many cases of poisoning and dangerous side effects have been reported. In order to discover the causes of death in forensic medicine is usually examine tissue samples taken from the body, although the results of toxicology tests generally give us more information, but identifying the pathological effects of Tramadol on the internal organs, especially the livers can be very helpful. Methods: In this cross-sectional study, information on the history, the autopsy report and toxicology testing of patients who died due to poisoning Tramadol were studied. In this study, all of the information already provided by the use of particular forms collected and then analyzed using computer software SPSS. Results: A total of 49 cadavers were examined in this study. There were 39 dead (80%) of men and 10 of (20%) women. Most common age groups in the study were 24 to 34 years old (41%), 15 to 24 years old (39%), were reported. There were significant difference between liver microscopic spread among different ages, history of Tramadol, positive and negative toxicology tests stomach contents, urine, blood, tissue and vitreous. Most common pathological changes were in liver, degenerative changes and inflammatory cell infiltration in patients who under 35 years old. Conclusion: In this study, the majority of patients had acute poisoning with Tramadol, it can be concluded that the majority of changes in tissue obtained was as a result of acute Tramadol, respectively incidence of atelectasis and edema and alveolar bleeding in the liver were most pathological findings. In reviewing toxicology, Tramadol are also present in the stomach contents, urine, gall bladder, liver and blood were positive, the result of stomach contents will be most helpful for us. Copyright © 2016 Forensic Medicine and Toxicology Department. All rights reserved120827E Not in FileB?9Almansour, M.I. Alferah, M.A. Shraideh, Z.A. Jarrar, B.M.2017MZinc oxide nanoparticles hepatotoxicity: Histological and histochemical study)Environmental Toxicology and Pharmacology-online early: doi: 10.1016/j.etap.2017.02.015not published, 01 Mar 17DAffect apoptosis BIOPSY CELL COMPARISON Content COSMETIC DIAGNOSIS dose EXPOSURE HEALTH HEPATIC HEPATOTOXICITY HUMAN Human health INFORMATION IS LIVER liver biopsy MALE MEMBRANE NANOPARTICLES NECROSIS NO NPS Organs OXIDATIVE STRESS PATHOGENESIS RAT rats RISK STRESS STUDY TISSUE Toxicities TOXICITY TREATMENT ZINC ZINC OXIDE 2/16/20177Zinc oxide nanoparticles (ZnO NPs) are widely used in industry and cosmetic products with promising investment in medical diagnosis and treatment. However, these particles may reveal a high potential risk for human health with no information about hepatotoxicity that might be associated with their exposure. The present work was carried out to investigate the histological and histochemical alterations induced in the hepatic tissues by naked 35nm ZnO NPs. Male Wistar albino rats were exposed to ZnO NPs at a daily dose of 2mg/kg for 21days. Liver biopsies from all rats under study were subjected to histopathological examinations. In comparison with the control rats, the following histological and histochemical alterations were demonstrated in the hepatic tissues of rats exposed to ZnO NPs: sinusoidal dilatation, Kupffer cells hyperplasia, lobular and portal triads inflammatory cells infiltration, necrosis, hydropic degeneration, hepatocytes apoptosis, anisokaryosis, karyolysis, nuclear membrane irregularity, glycogen content depletion and hemosidrosis. The findings of the present work might indicate that ZnO NPs have potential oxidative stress in the hepatic tissues that may affect the function of the liver. More work is needed to elucidate the toxicity and pathogenesis of zinc oxide nanoparticles on the vital organs120992, field[33]: Not in File0?.Almario, E.E.N. Borlak, J. Suzuki, A. Chen, M.2017Drug-induced liver injury2461694BioMed Research International2017ACID ACUTE As ASSAY chemical CLINICAL Cut-off DATA Development DILI dose DRUG drug induced liver injury drug-induced Drug-induced liver injury drugs EDITORIAL evidence HEPATIC HEPATOTOXICITY HUMAN IN VITRO injuries Injury IS LIVER liver injury METABOLITE Metabolites MODEL PAPER PATIENT PREDICTION REVIEW RISK STUDY THERAPEUTIC Toxicities TOXICITY TRIAL use VALPROIC ACID WITHDRAWAL Zebrafish2017120857& field[33]: Not in File ?JAltan, S. Ogurtan, Z.2017_Dimethyl sulfoxide but not indomethacin is efficient for healing in hydrofluoric acid eye burns232-244Burns431KACID agent Anti-inflammatory ANTI-INFLAMMATORY AGENTS ANTIOXIDANT apoptosis As Burn BURNS CELL CLINICAL CONJUNCTIVITIS corneal erosion DIMETHYLSULFOXIDE DMSO DRUG EFFICACY EYE healing HYDROFLUORIC ACID indomethacin INFLAMMATION INTRAOCULAR INTRAOCULAR PRESSURE IS MALE method methods NITRIC OXIDE NO RABBIT S STATUS STUDY TREATMENT2/2017Introduction In this study, we aimed to investigate the effect of indomethacin and dimethyl sulfoxide (DMSO), well-known antioxidant and anti-inflammatory agents, to heal eye burns induced with hydrofluoric acid in rabbits. Methods After general anesthesia, the right eye of 72 male New Zealand rabbits were burned by instillation of 2% hydrofluoric acid for 60 s. Following this, the eyes were irrigated with 500 cc normal saline. The rabbits were then divided into four groups of 18 rabbits each. Group D was instilled dimethyl sulfoxide 40%, Group I indomethacin 0.1%, and Group DI dimethyl sulfoxide together with indomethacin for 2, 7, and 14 treatment days, respectively. Group C received no instilled drug as control. Treatment efficacies were evaluated as clinical (corneal haziness, conjunctival status, conjunctivitis, corneal erosion area, and intraocular pressure) and histopathological (inflammatory cell infiltration, vascularization, stromal thickness, reepithelization, proliferating cell nuclear antigen [PCNA], apoptosis, and inducible nitric oxide synthases [iNOS]). Results In terms of corneal haziness and erosion area at days 7 and 14, group D showed the best result statistically as compared to the other groups. This group also showed the best result statistically for reepithelization rate, stromal thickness, and inflammatory cell end at day 14 as compared to the other groups. Conclusions Dimethyl sulfoxide (40%) was efficient to induce reepithelization on mild hydrofluoric acid eye burns, whereas 0.1% indomethacin both alone and along with DMSO poorly induced reepithelization and exacerbated inflammation. Thus, 40% DMSO could be used for the treatment of corneal disorders120747- field[33]: Not in File ?Alves, I.L. Vállez Garcia, D. Parente, A. Doorduin, J. Dierckx, R. Marques da Silva, A.M. Koole, M. Willemsen, A. Boellaard, R.2017EPharmacokinetic modeling of [11C]flumazenil kinetics in the rat brain17EJNMMI Research71analysis ANIMAL BRAIN DISTRIBUTION dose FITS FLUMAZENIL HUMAN INFORMATION KINETICS MALE Measurement MODEL P PET pharmacokinetic Pharmacokinetic modeling quality quantification RAT rats STUDY TISSUE Volume Wistar rat Wistar rats12/2017BACKGROUND: Preferred models for the pharmacokinetic analysis of [11C]flumazenil human studies have been previously established. However, direct translation of these models and settings to animal studies might be sub-optimal. Therefore, this study evaluates pharmacokinetic models for the quantification of [11C]flumazenil binding in the rat brain. Dynamic (60 min) [11C]flumazenil brain PET scans were performed in two groups of male Wistar rats (tracer dose (TD), n = 10 and pre-saturated (PS), n = 2). Time-activity curves from five regions were analyzed, including the pons (pseudo-reference region). Distribution volume (VT) was calculated using one- and two-tissue compartment models (1TCM and 2TCM) and spectral analysis (SA). Binding potential (BPND) was determined from full and simplified reference tissue models with one or two compartments for the reference tissue (FRTM, SRTM, and SRTM-2C). Model preference was determined by Akaike information criterion (AIC), while parameter agreement was assessed by linear regression, repeated measurements ANOVA and Bland-Altman plots. RESULTS: 1TCM and 2TCM fits of regions with high specific binding showed similar AIC, a preference for the 1TCM, and good VT agreement (0.1% difference). In contrast, the 2TCM was markedly preferred and necessary for fitting low specific-binding regions, where a worse VT agreement (17.6% difference) and significant VT differences between the models (p < 0.005) were seen. The PS group displayed results similar to those of low specific-binding regions. All reference models (FRTM, SRTM, and SRTM-2C) resulted in at least 13% underestimation of BPND. CONCLUSIONS: Although the 1TCM was sufficient for the quantification of high specific-binding regions, the 2TCM was found to be the most adequate for the quantification of [11C]flumazenil in the rat brain based on (1) higher fit quality, (2) lower AIC values, and (3) ability to provide reliable fits for all regions. Reference models resulted in negatively biased BPND and were affected by specific binding in the pons of the rat120982, field[33]: Not in File?8Amiri, H. Zamani, N. Hassanian-Moghaddam, H. Shadnia, S.2016`Cardiotoxicity of tricyclic antidepressant treated by 2650 mEq sodium bicarbonate: A case report2048004016682178JRSM Cardiovascular Disease5ACUTE ANTIDEPRESSANTS BICARBONATE CARDIOTOXICITY case CASE REPORT Case-report dose HYPOTENSION INTRAVENOUS IS Long term Long-term MORTALITY PATIENT POISONING SODIUM SODIUM BICARBONATE STATUS STATUS EPILEPTICUS Toxicities TOXICITY TRICYCLIC ANTIDEPRESSANTS WHO1/2016Poisoning with tricyclic antidepressants is an important cause of drug-related self-poisoning in the developed world and a very common cause of poisoning and mortality in developing countries. Electrocardiographic manifestations of most tricyclic antidepressant-poisoned patients resolve by the administration of 1-2 mEq/kg of sodium bicarbonate. Some rare cases have been reported who have been resistant to the long-term or high doses of bicarbonate administration. We present a case of acute tricyclic antidepressant toxicity referring with status epilepticus, hypotension, and refractory QRS complex widening that resolved after the intravenous administration of 2650 mEq sodium bicarbonate121066- field[33]: Not in FilePF?AAnastasopoulou, S. Komuda, M. Presman, B. Karlsson, M. Tomson, T.2017Svår reaktion av antiepileptikum hos kvinna med ursprung från Asien - Karbamazepininducerat Stevens–Johnsons syndrom/toxisk epidermal nekrolys vanligare hos personer med viss asiatisk härkomstLakartidningen114Adverse ADVERSE EFFECTS ANTICONVULSANT anticonvulsants CARBAMAZEPINE DERMAL EPILEPSY IS Occurrence PATIENT Population RISK SCREENING Stevens-Johnson Syndrome/Toxic epidermal necrolysis Syndrome TREATMENT 2/21/2017Stevens-Johnson syndrome/toxic epidermal necrolysis after initiation of carbamazepine in a HLA-B*15:02 gene carrier - screening in risk patients is recommended A 32-year-old woman, adopted from Indonesia, developed Stevens-Johnsons syndrome (SJS)/toxic epidermal necrolysis (TEN) after initiating carbamazepine treatment for epilepsy. SJS and TEN are rare but life-threatening adverse effects of carbamazepine, with a 72-100% risk of occurrence in patients carrying the HLA-B*15:02 allele. The HLA-B*15:02 allele is common in several Asian groups but less prevalent in European populations. Screening for HLA-B*15:02, or choice of medication other than aromatic anticonvulsants in patients with Asian ancestry, is recommended when treatment with carbamazepine is considered121177+ field[22]: [Severe reaction of anticonvulsants in women originating from Asia - Carbamazepine-induced Stevens-Johnson syndrome / toxic epidermal necrolysis common in people with certain Asian descent]. In Swedish with English abstract Not in File uB?+Andonian, D.O. Seaman, S.R. Josephson, E.B.2017kProfound hypotension and bradycardia in the setting of synthetic cannabinoid intoxication – A case series&American Journal of Emergency Medicine-online early: doi: 10.1016/j.ajem.2017.01.011not published, 01 Mar 17:ABUSE ACUTE Acute kidney injury Agitation As BRADYCARDIA CANNABINOID cannabinoids CANNABIS CARDIOTOXICITY CARDIOVASCULAR case CHEST PAIN Cohort CONFUSION DESIGNER DRUGS Emergencies emergency EMERGENCY DEPARTMENT HALLUCINATIONS HEALTH HEART HYPERTENSION HYPOTENSION injuries Injury INTOXICATION INTRAVENOUS K2 KIDNEY kidney injury Nausea NOVEL PSYCHOACTIVE SUBSTANCES outbreak pain PATIENT Poison PUBLIC PUBLIC HEALTH safe seizure SEIZURES STROKE STUDY SYMPTOMS SYNTHETIC CANNABINOID Synthetic cannabinoids TACHYCARDIA Texas Toxicities TOXICITY use Vital signs Volume WHO 1/12/2017Cannabinoids are the most commonly used illegal substances in the world [1]. Synthetic Cannabinoids (SCB) are also known as "Spice", "K2", "Spike", "herbal incense", "Cloud 9", "Mojo" and many others are becoming a large public health concern due to their increasing use, unpredictable toxicity, and abuse potential [2]. The most common reported toxicities with SCB use based on studies using Texas Poison control record are tachycardia, agitation and irritability, drowsiness, hallucinations, delusions, hypertension, nausea, confusion, dizziness, vertigo, chest pain, acute kidney injury, seizures, heart attacks and both ischemic and hemorrhagic strokes [3]. The Emergency Department (ED) here at Lincoln Medical Center has certainly seen a sizeable volume of K2 abusers who present displaying a spectrum of symptoms as noted above. However, during a concentrated outbreak of K2 use in the summer of 2015, a large cohort of patients presented with a toxidrome not previously described in any published literature. This included marked bradycardia and hypotension while maintaining global neurologic function. Although these patients were drowsy and sleepy at presentation, tactile stimuli would arouse these patients to awaken and participate in an interview. The patients described in this case series, appeared to be on the brink of cardiovascular collapse. The vital signs however normalized with intravenous fluid (IVF) hydration only, over the course of 6 to 7h, allowing a safe discharge from the ED120935, field[33]: Not in File RB?bAnsari, M.A. Raish, M. Ahmad, A. Alkharfy, K.M. Ahmad, S.F. Attia, S.M. Alsaad, A.M. Bakheet, S.A.2017Sinapic acid ameliorate cadmium-induced nephrotoxicity: In vivo possible involvement of oxidative stress, apoptosis, and inflammation via NF-kappaB downregulation)Environmental Toxicology and Pharmacology-online early: doi: 10.1016/j.etap.2017.02.014not published, 01 Mar 17ACID Anti-inflammatory ANTIOXIDANT antioxidant enzymes apoptosis Bax CADMIUM CALCIUM CATALASE Cd CREATININE cytokine ENVIRONMENTAL ENZYME IL-6 IN VITRO IN VIVO INDUSTRIAL INFLAMMATION injuries Injury KIDNEY LEAD LEVELS LIPID LIPID PEROXIDATION MECHANISM NEPHROTOXICITY NITRIC OXIDE NO OXIDATIVE STRESS OXYGEN PEROXIDATION Pollutant PRETREATMENT PROTEIN RENAL ROS SERUM SPECIES STRESS TREATMENT UREA 2/15/2017Cadmium (CD), an environmental and industrial pollutant, generates reactive oxygen species (ROS) and NOS responsible for oxidative and nitrosative stress that can lead to nephrotoxic injury, including proximal tubule and glomerulus dysfunction. Sinapic acid (SA) has been found to possess potent antioxidant and anti-inflammatory effects in vitro and in vivo. We aimed to examine the nephroprotective, anti-oxidant, anti-inflammatory, and anti-apoptotic effects of SA against CD-induced nephrotoxicity and its underlying mechanism. Kidney functional markers (serum urea, uric acid, creatinine, LDH, and calcium) and histopathological examinations of the kidney were used to evaluate CD-induced nephrotoxicity. Oxidative stress markers (lipid peroxidation and total protein), renal nitrosative stress (nitric oxide), antioxidant enzymes (catalase and NP-SH), inflammation markers (NF-kappaB [p65], TNF-alpha, IL-6, and myeloperoxidase [MPO]), and apoptotic markers (caspase 3, Bax, and Bcl-2) were also assessed. SA (10 and 20mg/kg) pretreatment restored kidney function, upregulated antioxidant levels, and prevented the elevation of lipid peroxidation and nitric oxide levels, significantly reducing oxidative and nitrosative stress. CD upregulated renal cytokine levels (TNF-alpha, IL-6), nuclear NF-kappaB (p65) expression, NF-kappaB-DNA-binding activity, and MPO activity, which were significantly downregulated upon SA pretreatment. Furthermore, SA treatment prevented the upregulation of caspase 3 and Bax protein expression and upregulated Bcl-2 protein expression. SA pretreatment also alleviated the magnitude of histological injuries and reduced neutrophil infiltration in renal tubules. We conclude that the nephroprotective potential of SA in CD-induced nephrotoxicity might be due to its antioxidant, anti-inflammatory, and anti-apoptotic potential via downregulation of oxidative/nitrosative stress, inflammation, and apoptosis in the kidney120991, field[33]: Not in FilesB?Api, A.M. Belsito, D. Bhatia, S. Bruze, M. Calow, P. Dagli, M.L. Dekant, W. Fryer, A.D. Kromidas, L. La Cava, S. Lapczynski, A. Liebler, D.C. O'Brien, D. Parakhia, R. Penning, T.M. Politano, V.T. Ritacco, G. Salvito, D. Schultz, T.W. Shen, J. Sipes, I.G. Wall, B. Wilcox, D.K.2017iRIFM fragrance ingredient safety assessment, Isobornyl 2-methylpropionate, CAS Registry Number 85586-67-0Food and Chemical Toxicology,online early: doi: 10.1016/j.fct.2017.02.012not published, 01 Mar 17DASSESSMENT ca FRAGRANCE Ingredient Registry SAFETY safety assessment 2/17/2017121013+ field[33]: Not in File;B?'Arens, A. Olives, T. Laes, JA. Cole, J.2017It's not just heroin anymoreClinical Toxicology0online early: doi: 10.1080/15563650.2017.1286015not published, 03 Mar 17HAdulterant ADULTERANTS As author CLINICAL dose duration Environment EPIDEMIC EXPOSURE fatalities fatality FENTANYL HEROIN INTOXICATION IS LETTER MANAGEMENT MENTAL STATUS NALOXONE NO Observation OPIOID Opioids OVERDOSE PATIENT Pharmaceuticals REVIEW STATUS Synthetic Opioid Time TOXICOKINETIC toxicokinetics TRANSPORT Vital signs 2/16/2017121150/ field[33]: Not in File ?)Arfken, C.L. Suchanek, J. Greenwald, M.K.2017;Characterizing fentanyl use in methadone-maintained clients17-21J Subst Abuse Treat75dABUSE ALPRAZOLAM COCAINE DATA DEATH Deaths DISTRIBUTION DRUG EXPOSURE FENTANYL GAP HEROIN HYDROCODONE IS maintenance maintenance treatment METABOLITE Metabolites METHADONE Methadone maintenance Methadone maintenance therapy method methods Michigan MORPHINE NALOXONE prevalence REVIEW SUBSTANCE ABUSE SURVEY Testing THERAPY TREATMENT UNITED STATES URINE use4/2017AIMS: Deaths attributed to fentanyl have increased in the United States. However, little is known about fentanyl use among substance abuse treatment clients. To fill this gap, we assessed prevalence of fentanyl exposure, characteristics of clients testing positive for fentanyl, other substances detected concurrently or simultaneously with fentanyl, and clients' perception of how many people are actively seeking to use fentanyl. METHODS: A retrospective chart review was conducted of all clients at one methadone maintenance treatment clinic between January 2015 and May 2016 in Wayne County, Michigan. Urine drug screens (UDS) including fentanyl (and its metabolite norfentanyl) were conducted clinically. To obtain additional data, 113 clients in this clinic subsequently completed an anonymous survey. RESULTS: Of 368 unique clients with UDS, 38.0% had at least one and 26.1% had >/=2 fentanyl-positive UDS results. None had a fentanyl prescription. Clients ever testing positive for fentanyl were significantly (p<0.05) more likely to use cocaine, have multiple treatment admissions to the clinic, and leave treatment sooner. Fentanyl-positive UDS results coincided most commonly with metabolites of cocaine- and heroin-positive UDS results. Of the anonymously surveyed clients, most (67.3%) reported they did not know anyone seeking fentanyl, a proportion significantly higher than for heroin, cocaine, alprazolam, hydrocodone and morphine. CONCLUSIONS: Fentanyl was commonly detected during this period with some clients having multiple fentanyl-positive UDS. Most clients did not know anyone seeking to obtain fentanyl. Regardless, the high exposure underscores that naloxone training and distribution is needed121064, field[33]: Not in File5B?%Ashauer, R. O'Connor, I. Escher, B.I.20176Toxic mixtures in time - the sequence makes the poison"Environmental Science & Technology*online early: doi: 10.1021/acs.est.6b06163not published, 28 Feb 17As ASSESSMENT chemical CHEMICALS DIAZINON dose evidence EXPOSURE Homeostasis IS method methods NO Poison PROPICONAZOLE PROXY recovery RISK RISK ASSESSMENT TEST Time toxic Toxicant Toxicities TOXICITY TOXICOKINETIC TOXICOLOGY2/8/2017S"The dose makes the poison." This principle assumes that once a chemical is cleared out of the organism (toxicokinetic recovery), it no longer has any effect. However, it overlooks the other process of re-establishing homeostasis, toxicodynamic recovery, which can be fast or slow depending on the chemical. Therefore, when organisms are exposed to two toxicants in sequence, the toxicity can differ if their order is reversed. We test this hypothesis with the freshwater crustacean Gammarus pulex and four toxicants that act on different targets (diazinon, propiconazole, 4,6-dinitro-o-cresol, 4-nitrobenzyl chloride). We found clearly different toxicity when the exposure order of two toxicants was reversed, while maintaining the same dose. Slow toxicodynamic recovery caused carry-over toxicity in subsequent exposures, thereby resulting in a sequence effect - but only when toxicodynamic recovery was slow relative to the interval between exposures. This suggests that carry-over toxicity is a useful proxy for organism fitness and that risk assessment methods should be revised as they currently could underestimate risk. We provide the first evidence that carry-over toxicity occurs amongst chemicals acting on different targets and when exposure is several days apart. It is therefore not only the dose that makes the poison but also the exposure sequence120879) field[33]: Not in File B?Auclin, E. Bourillon, C. De Maio, E. By, M.A. Seddik, S. Fournier, L. Auvray, M. Dautruche, A. Vano, Y.-A. Thibault, C. Joly, F. Brunereau, L. Gomez-Roca, C. Chevreau, C. Elaidi, R. Oudard, S.2017Prediction of everolimus toxicity and prognostic value of skeletal muscle index in patients with metastatic renal cell carcinomaClinical Genitourinary Cancer-online early: doi: 10.1016/j.clgc.2017.01.022not published, 01 Mar 17.Age analysis ANTINEOPLASTIC DRUGS As baseline Body mass index CARCINOMA CELL Cohort computed tomography DATABASE DOE DRUG drugs method methods Multivariate analysis MUSCLE NO P PATIENT PREDICTION RENAL Renal cell carcinoma SKELETAL MUSCLE STUDY SURVIVAL THERAPY TOMOGRAPHY Toxicities TOXICITY TREATMENT2/1/2017BACKGROUND: The objective of the study was to assess the prognostic role of skeletal muscle index (SMI) in metastatic renal cell carcinoma (mRCC) patients treated with everolimus, and its effect of on everolimus-induced toxicity. PATIENTS AND METHODS: Consecutive mRCC patients treated with everolimus between February 2007 and November 2014 underwent computed tomography scans at a single center performed by the same radiologist. SMI was assessed before everolimus treatment using the L3 cross-sectional area. Overall survival (OS) was analyzed according to SMI value. Results were adjusted using the International Metastatic Database Consortium (IMDC) prognostic group, body mass index (BMI), and/or number of previous tyrosine kinase inhibitor lines (NPL). RESULTS: One hundred twenty-four mRCC patients (mean age, 60.21 years) were treated with everolimus as second- or third-line (82.3%) or > third-line (17.7%) therapy. Most patients (87.9%) had clear cell carcinoma. IMDC prognostic group was "favorable" (32.3%), "intermediate" (50%), or "poor" (17.7%). Median SMI was 40.75. OS was longer in patients from the highest versus lowest SMI tercile: 21.9 versus 10 months (P = .002). Continuous SMI at baseline was not significantly associated with OS after adjustment for IMDC prognostic group, BMI, or NPL but the highest versus lowest SMI tercile was an independent prognostic factor in multivariate analysis (P = .025). There was no difference in everolimus toxicity between SMI tercile groups. CONCLUSION: SMI was an independent prognostic factor for mRCC patients treated with everolimus. Whether this provides additional prognostic value to IMDC criteria needs to be confirmed in a larger cohort. SMI does not seem to be predictive of everolimus-induced toxicity120969, field[33]: Not in File BB?kAvci, H. Epikmen, E.T. Ipek, E. Tunca, R. Birincioglu, S.S. Aksit, H. Sekkin, S. Akkoc, A.N. Boyacioglu, M.2017WProtective effects of silymarin and curcumin on cyclophosphamide-induced cardiotoxicity&Experimental and Toxicologic Pathology,online early: doi: 10.1016/j.etp.2017.02.002not published, 01 Mar 17ADULT agent ANIMAL ANTIOXIDANT CARDIOTOXICITY CELL CLINICAL cp CURCUMIN CYCLOPHOSPHAMIDE DNA EVALUATION FEMALE HAEMORRHAGE HEART IS IV LEAD LEVELS MDA method methods MUSCLE NECROSIS OEDEMA OXIDATIVE STRESS PROTEIN RAT rats SILYMARIN STATUS STRESS STUDY TISSUE toxic toxic effects use 2/21/2017 INTRODUCTION: Cyclophosphamide (CP) is a potent anticancer agent; its clinical use is limited due to its marked cardiotoxicity. AIM: The present study was aimed at evaluating the cardioprotective effects of silymarin (SLY) and curcumin (CUR), which have strong antioxidant properties, against the toxic effects of high-dose CP on the heart of rats. MATERIALS AND METHODS: A total of 36 adult Wistar albino female rats were randomly divided into six groups. Group I (control group; nothing was administered), Group II (CP group; 30mg/kg/day CP was administered intraperitoneally to each animal for seven days), Group III (SLY group; 100mg/kg/day SLY by gavage for 14 days), Group IV (CUR group; 100mg/kg/day CUR by gavage for 14 days), Group V (SLY+CP group; 100mg/kg/day SLY by gavage for 14days plus 30mg/kg/day CP intraperitoneally starting from the seventh day) and Group VI (CUR+CP group; 100mg/kg/day CUR by gavage for 14days plus 30mg/kg/day CP intraperitoneally starting from the seventh day). Biochemical, histopathological and immunohistochemical methods were utilised for evaluation of the cardiotoxicity. RESULTS: The result showed that an increase in heart MDA and DNA fragmentation levels were detected while significant decreases were seen in SOD levels in CP alone group when compared to the other groups. CP caused severe damage in the histopathological status of heart tissue including intersititial oedema, haemorrhage, degeneration and necrosis in muscle fibrils and perinuclear vacuolization. A significant increase in the percentage of TUNEL-positive cells and gammaH2AX protein expression was detected in the CP-treated group compared to the control and other treated groups. There was significant increase in the percentage of caspase 3-positive cells and decrease in the percentage of Bcl-2 positive cells in the CP group compared to the control group and other treated groups. However, a significant decrease in the percentage of cTnI and cTnT immunoreactivity was also observed in the CP-treated group compared to the control and other treated groups. In the groups in which SLY and CUR were administered concurrently with CP, biochemical parameters, histopathological and immunohistochemical results were found to be significantly lower than in the CP-only group. CONCLUSIONS: These results lead to conclusion that the natural antioxidant SLY and CUR might have protective effects against CP-induced cardiotoxicity and oxidative stress in rats121005+ field[33]: Not in File$??Avula, B. Sagi, S. Wang, Y.H. Wang, M. Navarro, V.J. Khan, I.A.2016TChemical analysis of dietary supplements that have been implicated in hepatotoxicityPA8 Planta Medica8257ABSTRACT AFLATOXIN ALKALOIDS AMATOXINS ANABOLIC STEROID Anabolic steroids analysis As chemical Chemical analysis COMFREY CONTAMINATION DATABASE Development DIETARY Dietary supplement Dietary supplements DRUG drug induced liver injury drug-induced evidence GREEN TEA HD HEALTH HEPATOTOXICITY HERBAL MEDICINE HUMAN IDENTIFICATION INFORMATION Ingredient injuries Injury INTERACTION IS LC-MS LIVER liver injury Medicine medicines METABOLITE Metabolites MUSHROOM NO NSAID NSAIDs Pharmaceuticals PYRROLIZIDINE Pyrrolizidine alkaloids standards STEROID US WEIGHT Weight Loss2016120707( field[33]: Not in File?9Aygun, C. Altinok, A.Y. Çakir, A. Agan, A.F. Balaban, Y.2016[Acute temozolomide induced liver injury: mixed type hepatocellular and cholestatic toxicity487-489 Acta Gastro-Enterologica Belgica794rACUTE agent ALANINE ALKALINE analysis ASSESSMENT Bilirubin BIOPSY case causality DIAGNOSIS discontinuation DRUG drug-induced Fatigue HEPATIC HEPATITIS HEPATOTOXICITY HI injuries Injury INR IS JAUNDICE Laboratories LABORATORY LEAD LIVER liver biopsy LIVER FUNCTION liver injury MALE Nausea ORAL PATIENT recovery S SCALE TEMOZOLOMIDE TEST Toxicities TOXICITY TREATMENT use9/2016ZTemozolomide (TMZ) is an oral imidazotetrazine methylating agent which is used for the treatment of glioblastoma multiforme (GBM). We report a case of acute hepatotoxicity in a 53-year old male patient after administration of TMZ for GBM. He had fatigue, nausea, anorexia and jaundice. His laboratory analysis showed alanine aminotransferase(ALT): 632 IU/L (normal range 0-40); aspartate aminotransferase(AST): 554 IU/L (normal range 5-34); alkaline phosphatase(ALP): 1143 IU/L (normal range 40-150); gamma-glutamyl transpeptidase(GGT): 514 IU/L (normal range 9-64 IU/L); total bilirubin: 15.1 mg/dL (normal range 0-1.2); direct bilirubin: 13.2 mg/dL and prothrombin time(PT): 13.5 s, with international normalized ratio (INR): 1.1 (normal range 0.8-1.2). His liver biopsy specimen showed mixed-type (both hepatocellular and cholestatic) hepatic injury, compatible with a diagnosis of drug-induced hepatitis. An objective causality assessment using the Naranjo probability scale suggested that TMZ was the probable cause of the acute hepatitis. His liver function tests gradually normalized in 6 months after discontinuation of the drug. In susceptible individuals, TMZ use may lead to acute mixed type liver toxicity. Complete recovery may be possible if the drug is discontinued before severe liver injury is established. (Acta gastroenterol. belg., 2016, 79, 487-489)120929+ Not in File?Baker, S. Fairchild, A.2016,Radiation-induced esophagitis in lung cancer119-127 Lung Cancer: Targets and Therapy7ACID ACUTE Acute toxicity adherence analgesic ANALGESICS As CANCER CHEMOTHERAPY DIET dose Esophageal esophageal stricture Incidence IS LATE LUNG lung cancer maintenance MANAGEMENT RADIATION RADIOTHERAPY RISK SEVERITY STRICTURE SYMPTOMS TECHNIQUE Toxicities TOXICITY TREATMENT2016(Radiation-induced esophagitis is the most common local acute toxicity of radiotherapy (RT) delivered for the curative or palliative intent treatment of lung cancer. Although concurrent chemotherapy and higher RT dose are associated with increased esophagitis risk, advancements in RT techniques as well as adherence to esophageal dosimetric constraints may reduce the incidence and severity. Mild acute esophagitis symptoms are generally self-limited, and supportive management options include analgesics, acid suppression, diet modification, treatment for candidiasis, and maintenance of adequate nutrition. Esophageal stricture is the most common late sequela from esophageal irradiation and can be addressed with endoscopic dilatation. Approaches to prevent or mitigate these toxicities are also discussed121067( field[33]: Not in File $B? @Bao, W. Cao, C. Li, S. Bo, L. Zhang, M. Zhao, X. Liu, Y. Sun, C.2017QMetabonomic analysis of quercetin against the toxicity of acrylamide in rat urineFood & Function%online early: doi: 10.1039/c6fo01553knot published, 01 Mar 17*ACID ACRYLAMIDE AMINO ACID analysis ANTIOXIDANT Antioxidant defense system Biomarker BIOMARKERS COMPARISON DRINKING WATER EXPOSURE liquid chromatography/mass spectrometry METABOLISM METABOLITE Metabolites P RAT rats Regulation RESEARCH SPECTROMETRY sulfate Toxicities TOXICITY TREATMENT URINE WATER 2/22/2017This research aims to determine whether quercetin has protective effects against the toxicity of acrylamide (AA) using metabonomic technology. Randomly, the rats were assigned into a control group, AA treatment group, quercetin treatment group and quercetin plus AA treatment group. Quercetin and AA were administered to rats daily via gavage and drinking water for 16 weeks, respectively. To detect the metabonomic profiles of urine, ultra-performance liquid chromatography/mass spectrometry was used. A total of 15 metabolites, including biomarkers of AA exposure (GAMA, AAMA, and iso-AAMA) and quercetin exposure (quercetin and isorhamnetin), were identified. In comparison with the control group, the intensities of GAMA, AAMA, iso-AAMA, 1-salicylate glucuronide, vinylacetylglycine, PE(20:1(11Z)/14:0), 7-ketodeoxycholic acid, cysteic acid, p-cresol sulfate, and l-cysteine in the AA-treated group were statistically significantly increased (p < 0.01), and the intensities of 2-indolecarboxylic acid, 3-acetamidobutanal, and kynurenic acid in the AA-treated group were statistically significantly decreased (p < 0.01). The above-mentioned metabolites were significantly ameliorated in the quercetin (50 mg per kg bw) plus AA-treated group compared with the AA-treated group (p < 0.01 or p < 0.05). However, the intensities of these metabolites in the quercetin (50 mg per kg bw) plus AA-treated groups were still significantly different from those of the control group (p < 0.01 or p < 0.05). The above results suggest that quercetin has a partial protective effect on AA-induced toxicity. The protective effects include regulation of fatty acid metabolism and amino acid metabolism and enhancing the antioxidant defense system121012$ field[33]:!divAbstract Not in File?! Bartlett, D.2017Drug-induced serotonin syndrome49-54Critical Care Nurse371Affect As complications DEATH DETECTION DRUG drug-induced drugs duration effectiveness evidence FATAL IS METABOLISM MONOAMINE OXIDASE MONOAMINE OXIDASE INHIBITOR NO PATIENT SEROTONIN SEROTONIN SYNDROME SSRIs Syndrome TEST THERAPY TREATMENT2/2017Serotonin syndrome is a potentially fatal condition caused by drugs that affect serotonin metabolism or act as serotonin receptor agonists. Monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors are the medications most commonly associated with serotonin syndrome. Serotonin syndrome can be mild and of short duration, but a prolonged course, life-threatening complications, and death are possible. Detection of serotonin syndrome is not difficult if the diagnostic criteria are understood and properly used, but the syndrome has no confirmatory tests and other drug-induced syndromes can, to a degree, mimic serotonin syndrome. The treatment is symptomatic and supportive. Antidotal therapies are available, but the evidence for their effectiveness is limited. If serotonin syndrome is promptly identified and aggressively treated, the patient should fully recover120708$ field[33]: Not in File N?">Bayat, F. Akbari, S.A. Dabirioskoei, A. Nasiri, M. Mellati, A.2016:The relationship between blood lead level and preeclampsia 3450-3455Electron Physician812KABSORPTION Age analysis As BLOOD Blood lead BLOOD PRESSURE case-control case-control study complications DATA EDUCATION EXPOSURE HEALTH Heavy metal Hg HOSPITAL HOUSEHOLD income IS LEAD MECHANISM Mechanisms method methods OXIDATIVE STRESS PATIENT PREGNANCY Regression Analysis STRESS STUDY TEST TISSUE Tissue damage toxic UNIT WOMEN12/2016$INTRODUCTION: Lead is a heavy metal to which people are commonly exposed. One of the possible mechanisms of tissue damages caused by this toxic metal is oxidative stress, which in turn may cause numerous pregnancy complications such as preeclampsia. The present study was conducted to determine the relationship between maternal Blood Lead Level (BLL) and preeclampsia. METHODS: The present case-control study was conducted on 158 pregnant women admitted to a hospital in Zanjan, Iran, from August 2015 to March 2016. To measure their BLL, 1.5 cc of blood was drawn from each participant. The demographic and obstetric details of the patients were recorded in a form. The potentiometric method was used to test the samples. The data obtained were analyzed by SPSS version 22, using Mann-Whitney U test, the Chi square, independent-samples t-test, Pearson product-moment correlation, and simple linear regression analysis. RESULTS: The mean BLL was 6.24+/-1.74 mug/dl in the control group and 8.04+/-3.4 mug/dl in the preeclampsia group. The two groups were matching in terms of the mother's age and education and the household income. A significant relationship was observed between BLL and preeclampsia (p=0.028), as per every unit of increase (1 mug/dl) in BLL, systolic blood pressure increased by 0.014 mm Hg and diastolic blood pressure by 0.013 mm Hg (p=0.004). CONCLUSION: The results obtained suggest a relationship between BLL and preeclampsia. Global health measures should be taken to remove the exposure to lead so as to reduce its absorption by pregnant women120874 field[33]: Not in File?#FBazoukis, G. Papadatos, S.S. Michelongona, P. Fragkou, A. Yalouris, A.2017FAssessment and management of elemental mercury poisoning-a case report126-129Clinical Case Reports52ACUTE acute poisoning APPENDIX ASPIRATION ASSESSMENT BRONCHOALVEOLAR LAVAGE case CASE REPORT Case-report ELEMENTAL MERCURY INGESTION LAVAGE MANAGEMENT MERCURY PATIENT POISONING REMOVAL TREATMENT2/2017BWe describe a patient with elemental mercury aspiration and retention in the appendix after elemental mercury ingestion. Conservative management was proved to be successful for the removal of the mercury from the appendix while we do not suggest bronchoalveolar lavage in cases of small amount elemental mercury aspiration120865" field[33]: Not in File ?$J8Behar, E. Rowe, C. Santos, G.-M. Santos, N. Coffin, P.O.2017_Academic detailing pilot for naloxone prescribing among primary care providers in San Francisco122-126Family Medicine492CLINICAL DATA duration EVALUATION FOLLOW UP Follow-up IS method methods MODEL NALOXONE NALTREXONE OPIOID Opioids outcome PATIENT PRESCRIBING SAFETY use WHO2/2017BACKGROUND: Improving the safety of prescribed opioids in clinical settings is a national priority. While co-prescribing naloxone is increasingly recommended, there is little understanding of the optimal way to implement this practice. METHODS: We developed and delivered an academic detailing intervention to 40 randomly selected opioid-prescribing primary care providers in San Francisco from February to May 2015. Process outcomes were tracked and included provider demographics, number and type of contact attempts, reason for refusal (if applicable), name of detailer, duration of intervention, topics covered, provider concerns, and follow-up plan. Outcome evaluation included changes in the rate of naloxone prescriptions 4 months before and after academic detailing by provider based on de-identified Medi-Cal claims data. Using a difference-in-differences approach, we developed a negative binomial regression model to compare changes in naloxone prescribing to Medi-Cal patients between providers that did and did not receive the intervention. RESULTS: Eighty-three percent of 48 providers contacted accepted the intervention after a mean of 2.6 contacts. Detailing lasted a mean of 28 minutes (range 5-60 minutes) and most frequently covered indications for naloxone, examples of naloxone prescriptions, language to use with patients, and pharmacy outreach. Those who received the academic detailing had a significantly greater increase in naloxone prescriptions compared to those who did not receive the intervention (IRR=11.0, 95%CI=1.8-67.8, P=.010). CONCLUSIONS: Academic detailing addressing opioid safety and naloxone prescribing was well-received by primary care providers and associated with an increase in naloxone prescriptions filled by Medi-Cal patients1210067 Not in File ?% Belapurkar, P. Goyal, P. Kar, A.2016In vitro evaluation of bioremediation capacity of a commercial probiotic, Bacillus coagulans, for chromium (VI) and lead (II) toxicity272-276*Journal of Pharmacy and Bioallied Sciences84-ACID ACUTE acute poisoning ANTIBIOTIC Antibiotics As BILE BIOACCUMULATION Characterization CHROMIUM EFFICACY EVALUATION FATAL Heavy metal HEAVY METALS HUMAN Humans IN VITRO IN VIVO IS LEAD METALS method methods NO POISONING Pseudomonas Sensitivity SPECIES STUDY TOLERANCE Toxicities TOXICITY TREATMENT10/2016INTRODUCTION: The bioaccumulation of heavy metals including chromium (VI) (Cr (VI)) and lead (II) (Pb (II)) causes fatal toxicity in humans. Some naturally occurring bacterial genera such as Bacillus and Pseudomonas help in bioremediation of these heavy metals and some of the species of Bacillus are proven probiotics. However, no study has been conducted on Bacillus coagulans, which is a proven probiotic species of genus Bacillus. OBJECTIVES: The primary objective of the present study was to assess the potential of a proven probiotic, B. coagulans, marketed as "Sporlac-DS," to survive in the presence of Cr (VI) and Pb (II) and its ability to reduce its concentration in vitro. MATERIALS AND METHODS: The Minimum inhibitory concentration (MIC) of the organism for Cr (VI) and Pb (II) was determined followed by its biochemical and morphological characterization. Its antibiotic sensitivity and probiotic efficacy were assessed. Further, its bioremediation capacity was observed in vitro by determining the residual Cr (VI) and Pb (II) concentration after 72 h. RESULTS: B. coagulans could tolerate up to 512 ppm concentration of Cr (VI) and had an MIC of 128 ppm for Pb (II). After 72 h, the organism reduced 32 ppm Cr (VI) and 64 ppm Pb (II) by 93% and 89%, respectively. When B. coagulans was studied before and after growing on Cr (VI) and Pb (II) for 24 h, an increase was seen in sensitivity toward the tested antibiotics whereas no change was observed in morphological and biochemical characters. It also showed no change in their bile and acid tolerance, indicating that it retains its probiotic efficacy. CONCLUSION: The tested probiotic B. coagulans may have a potential role in bioremediation of Cr (VI) and Pb (II), in vivo121057- field[33]: Not in File?&GBenigni, R. Battistelli, C.L. Bossa, C. Giuliani, A. Tcheremenskaia, O.2017kEndocrine disruptors: data-based survey of in vivo tests, predictive models and the Adverse Outcome Pathway18-24&Regulatory Toxicology and Pharmacology86NAdverse alternative methods As ASSAY Characterization chemical CHEMICALS COMPARISON DATA DATABASE dose ENDOCRINE Endocrine Disruption Endocrine disruptor endocrine disruptors FISH IDENTIFICATION IN VITRO IN VIVO INTERACTION IS method methods MODEL ORAL outcome Pathway RECEPTORS Regulatory REPRODUCTION SURVEY TEST Toxicities TOXICITY 2/20/2017The protection from endocrine disruptors is a high regulatory priority. Key issues are the characterization of in vivo assays, and the identification of reference chemicals to validate alternative methods. In this exploration, publicly available databases for in vivo assays for endocrine disruption were collected and compared: Rodent Uterotrophic, Rodent Repeated Dose 28-day Oral Toxicity, 21-Day Fish, and Daphnia magna reproduction assays. Only the Uterotrophic and 21-Day Fish assays results correlated with each other. The in vivo assays data were viewed in relation to the Adverse Outcome Pathway, using as a probe 18 ToxCast in vitro assays for the ER pathway. These are the same data at the basis of the EPA agonist ToxERscore model, whose good predictivity was confirmed. The multivariate comparison of the in vitro/in vivo assays suggests that the interaction with receptors is a major determinant of in vivo results, and is the critical basis for building predictive computational models. In agreement with the above, this work also shows that it is possible to build predictive models for the Uterotrophic and 21-Day Fish assays using a limited selection of Toxcast assays121101- field[33]: Not in FileN?'JBenny, B. Anil, N. Umarani, R.2016^Study of prognostic indicators in organophosphate poisoning in tertiary care teaching hospital124-133Der Pharmacia Lettre817$ACCIDENTAL Age As case CLINICAL College DATA DIAGNOSIS DIMETHOATE Emergencies emergency FEMALE HOSPITAL INFORMATION INGESTION IS MALE MANAGEMENT MONOCROTOPHOS MORTALITY op organophosphate Organophosphates PATIENT Poison POISONING PROGNOSIS Pupil Rural STOMACH STUDY TERTIARY CARE Vomiting WHO2016_Organophosphate poisoning is encountered as an emergency problem in rural areas. OP poisoning can result from accidental ingestion and self-poisoning. This study was to evaluate patients diagnosed with organophosphate poisoning, to study the type of compound, its clinical features and to correlate prognosis of the organophosphate compound.The study was conducted for a period of 6 months [March 2016 to September 2016] in Rajah Muthiah Medical College Hospital, Annamalai University,1200 bedded multi-specialty tertiary care teaching hospital located in Tamil Nadu. All relevant data were collected from inpatient case records. A total of 100 patients were taken for this study. A total number of 100 patient's data were analyzed,in which majority of them were males (66%).The most affected age group were31-50 years (44%) in males and 18-30 years (50%) in females. The most common organophosphate compound is Monocrotophos and the least were Porphyrous, Dimethoate and Quinalophos. The most consistent clinical manifestations was vomiting and the least were fasciculation, pinpoint pupils and urination. Mortality rates were higher in patients who consumed higher amount of poison on empty stomach and delayed presentation to hospital. This study reveals that early diagnosis, effective management and establishing poison information center will reduce the mortality rates120709 Not in File ?(OBi, M.-J. Sun, X.-N. Zou, Y. Ding, X.-Y. Liu, B. Zhang, Y.-H. Guo, D.-D. Li, Q.2017TN-butylphthalide improves cognitive function in rats after carbon monoxide poisoning64Frontiers in Pharmacology8ACUTE analysis ANIMAL BRAIN Broad spectrum CALPAIN carbon CARBON MONOXIDE carbon monoxide poisoning CO cognitive cognitive dysfunction Cognitive function electron microscopy EXPOSURE Hippocampus HYPERBARIC OXYGEN hyperbaric oxygen therapy IMMUNOFLUORESCENCE IMPAIRMENT IS LEVELS MECHANISM MICROSCOPY MODEL OXYGEN P POISONING PROTEIN proteins RAT rats SEQUELAE STUDY THERAPY TISSUE TREATMENT2017Cognitive impairment is the most common neurologic sequelae after carbon monoxide (CO) poisoning, and the previous investigations have demonstrated that N-Butylphthalide (NBP) could exert a broad spectrum of neuroprotective properties. The current study aimed to investigate the effect of NBP on cognitive dysfunction in rats after acute severe CO poisoning. Rats were randomly divided into a normal control group, a CO poisoning group and a CO+NBP group. The animal model of CO poisoning was established by exposure to CO in a chamber, and then all rats received hyperbaric oxygen therapy once daily, while rats in CO+NBP group were administered orally NBP (6 mg/ 100g) by gavage twice a day additionally. The results indicated that CO poisoning could induce cognitive impairment. The ultrastructure of hippocampus was seriously damaged under transmission electron microscopy, and the expressions of calpain 1 and CaMK II proteins were significantly elevated after CO exposure according to the analysis of immunofluorescence staining and western blot. NBP treatment could evidently improve cognitive function, and maintain ultrastructure integrity of hippocampus. The expression levels of both calpain 1 and CaMK II proteins in CO+NBP group were considerably lower than that of CO poisoning group (P < 0.05). Taken together, this study highlights the molecular mechanism of cognitive dysfunction in rats after CO exposure via the upregulation of both calpain 1 and CaMK II proteins. The administration of NBP could balance the expressions of calpain 1 and CaMK II proteins and improve cognitive function through maintaining ultrastructural integrity of hippocampus, and thus may play a neuroprotective role in brain tissue in rats with CO poisoning121016( field[33]: Not in File DB?)Bigi, C. Tuccori, M. Bocci, G.2017Healthcare professionals and pharmacovigilance of pediatric adverse drug reactions: a 5-year analysis of Adverse Events Reporting System database of the Food and Drug AdministrationMinerva Pediatrica1online early: doi: 10.23736/S0026-4946.17.04733-8not published, 01 Mar 17>ACCIDENTAL ADOLESCENT ADR Adverse Adverse drug reaction adverse drug reactions adverse event Adverse events Age agent analysis As chemical Convulsion DATABASE DRUG drugs FDA FOOD INFANT Infants method methods neonate NEONATES OVERDOSE PAEDIATRIC PATIENT pediatric pharmacovigilance REACTIONS STUDY THERAPEUTIC Vomiting 2/17/2017aBACKGROUND: To analyze the Adverse Events Reporting System (AERS) database of the Food and Drug Administration (FDA), investigating the characteristics of pediatric adverse drug reactions (ADRs) and describing the effective participation of healthcare professionals in the reporting activity. METHODS: Reports of ADRs were obtained from the FDA website. Only ADRs in pediatric subjects (divided by age, by country and by professional category) were included into the analysis. The drugs suspected as primary cause of the ADRs in pediatric subjects and their principal anatomic group according to the Anatomical Therapeutic Chemical classification system were considered. To classify the ADRs, the Medical Dictionary for Regularity Activities terminology was adopted. RESULTS: Between 2008 and 2012, FDA collected 113,077 ADRs in pediatric patients. Of the total pediatric ADR reports, those performed by medical doctors were 32%, followed by consumers (26%) and healthcare professionals (25%). Most of the ADR reports were related to the adolescent group (39%). Healthcare professionals resulted the category with the highest rate of ADR reports in neonates and infants. Drugs acting on nervous system and antineoplastic/immunomodulating agents were the most involved the pediatric ADR reports. Pyrexia, convulsion, vomiting and accidental overdose were the reactions more reported both from healthcare professionals and medical doctors. CONCLUSIONS: The present study describes the pediatric ADR reports of the FDA database through healthcare professional's perspective, describing the various aspects of pediatric pharmacovigilance1210720 field[33]: Not in FileB?*DBischoff, K. Chiapella, A. Weisman, J. Crofton, L.M. Hillebrandt, J.2017GZinc toxicosis in a boxer dog secondary to ingestion of holiday garlandJournal of Medical Toxicology,online early: doi: 10.1007/s13181-017-0602-znot published, 01 Mar 17TACUTE acute renal failure anemia ANIMAL case case studies Case Study DEATH DIAGNOSIS Diarrhea dog Emergencies emergency evidence FAILURE FIBROSIS hemolytic anemia HEPATIC history hypernatremia INGESTION IS Medicine outcome pancreatic PATIENT POSTMORTEM PROGNOSIS RENAL RENAL FAILURE SERUM Source STOMACH STUDY toxic Veterinary Vomiting ZINC 2/21/20174INTRODUCTION: Increased admissions occur in small animal veterinary emergency clinics during some holidays, and some of the increased caseload is due to ingestion of toxic substances. This report documents zinc toxicosis contributing to the death of a dog after ingestion of holiday tinsel garland. CASE STUDY: A mature boxer dog presented with a 4-day history of vomiting and diarrhea. Radiodense foreign material was detected in the stomach and removed via gastrotomy. The patient clinically worsened over the next several days with evidence of hemolytic anemia, severe hypernatremia, and an elevated WBC count with a suspected dehiscence of the surgical site and acute renal failure. The serum zinc concentration was moderately elevated. Postmortem findings included surgical dehiscence from the gastrotomy and enterotomy sites, hepatic extramedullary hematopoiesis, hemoglobinuric nephrosis, and pancreatic fibrosis. The foreign material removed from the stomach also contained zinc. DISCUSSION: Ingestion of holiday tinsel garland made from metal-coated plastic film has not previously been implicated in zinc toxicosis. Zinc toxicosis has a good prognosis in veterinary medicine when diagnosed and treated promptly, but the unique source of zinc in this dog contributed to the delay in diagnosis and grave outcome in this case121050+ field[33]: Not in File?+Bloom, R. Amber, K.T.2017Identifying the incidence of rash, Stevens-Johnson syndrome and toxic epidermal necrolysis in patients taking lamotrigine: a systematic review of 122 randomized controlled trials139-141!Anais Brasileiros de Dermatologia9219Adverse adverse reactions Affect Antiepileptic As bipolar CUTANEOUS DERMAL Development DRUG EPILEPSY Incidence IS LAMOTRIGINE MET Monotherapy PAPER PATIENT RASH REACTIONS REVIEW Stevens-Johnson syndrome Stevens-Johnson Syndrome/Toxic epidermal necrolysis STUDY Syndrome systematic review toxic TREATMENT TRIAL use1/2017Lamotrigine is an antiepileptic drug used for the treatment of epilepsy, bipolar disorder and numerous off-label uses. The development of rash significantly affects its use. The most concerning of these adverse reactions is Stevens-Johnson syndrome/toxic epidermal necrolysis. We performed a systematic review of randomized controlled trials using lamotrigine as a monotherapy to quantify the incidence of cutaneous reactions, particularly Stevens-Johnson syndrome/toxic epidermal necrolysis. Of a total of 4,364 papers regarding lamotrigine, 122 studies met our inclusion and exclusion criteria. In total, 18,698 patients were included with 1,570 (8.3%) of patients experiencing an adverse dermatologic reaction. The incidence of Stevens-Johnson syndrome/toxic epidermal necrolysis was 0.04%120939/ field[33]: Not in FileH?,$Bommarito, P.A. Martin, E. Fry, R.C.2017\Effects of prenatal exposure to endocrine disruptors and toxic metals on the fetal epigenome333-350 Epigenomics93Adverse chemical CHEMICALS DNA DNA methylation ENDOCRINE Endocrine disruptor endocrine disruptors Environment ENVIRONMENTAL evidence EXPOSURE FETAL HEALTH HUMAN Human health Long term Long-term MECHANISM METALS microRNA outcome PREGNANCY PRENATAL Prenatal exposure REVIEW STUDY toxic3/2017OExposure to environmental contaminants during pregnancy has been linked to adverse outcomes at birth and later in life. The link between prenatal exposures and latent health outcomes suggests that these exposures may result in long-term epigenetic reprogramming. Toxic metals and endocrine disruptors are two major classes of contaminants that are ubiquitously present in the environment and represent threats to human health. In this review, we present evidence that prenatal exposures to these contaminants result in fetal epigenomic changes, including altered global DNA methylation, gene-specific CpG methylation and microRNA expression. Importantly, these changes may have functional cellular consequences, impacting health outcomes later in life. Therefore, these epigenetic changes represent a critical mechanism that warrants further study120996' field[33]: Not in FileB?-Boobis, A.R. Cohen, S.M. Dellarco, V.L. Doe, J.E. Fenner-Crisp, P.A. Moretto, A. Pastoor, T.P. Schoeny, R.S. Seed, J.G. Wolf, D.C.20170Response to Loomis et al Comment on Boobis et al&Regulatory Toxicology and early: doi: 10.1016/j.yrtph.2017.02.011not published, 01 Mar 176ASSESSMENT CARCINOGENICITY LETTER RISK RISK ASSESSMENT 2/16/2017121103- field[33]: Not in File?.Bouga, M. Combet, E.2015iSeaweed and seaweed-containing foods in the UK: focus on labeling, iodine content, toxicity and nutritionE304$Proceedings of the Nutrition Society74OCE54ABSTRACT ADULT ALGAE ARSENIC As ASSESSMENT Consumption Content DIET DIETARY edible EXPOSURE FEMALE FOOD HEALTH Heavy metal HEAVY METALS INFORMATION Ingredient Intake IODINE IS LEAD LIPID METALS mu PACKAGING Population SEAWEED Source STATISTICS SURVEY TOLERANCE Toxicities TOXICITY UK use vitamin VITAMINS WHO2015120710+ field[33]: Not in File !?/ABouvier, B.A. Elston, B. Hadland, S.E. Green, T.C. Marshall, B.D.2017Willingness to use a supervised injection facility among young adults who use prescription opioids non-medically: a cross-sectional study13Harm Reduction Journal141&ABUSE ADULT Age As DRUG Drug use drugs Environment FACILITIES FENTANYL HEROIN history INJECTION Injection drug use MALE method methods MISUSE MORTALITY NO OPIOID Opioids OVERDOSE prescription opioids RISK Risk factor RISK FACTORS Sex STUDY SUBSTANCE ABUSE use WHO Young Adult Young adults youth 2/20/2017BACKGROUND: Supervised injection facilities (SIFs) are legally sanctioned environments for people to inject drugs under medical supervision. SIFs currently operate in ten countries, but to date, no SIF has been opened in the USA. In light of increasing overdose mortality in the USA, this study evaluated willingness to use a SIF among youth who report non-medical prescription opioid (NMPO) use. METHODS: Between January 2015 and February 2016, youth with recent NMPO use were recruited to participate in the Rhode Island Young Adult Prescription Drug Study (RAPiDS). We explored factors associated with willingness to use a SIF among participants who had injected drugs or were at risk of initiating injection drug use (defined as having a sex partner who injects drugs or having a close friend who injects). RESULTS: Among 54 eligible participants, the median age was 26 (IQR = 24-28), 70.4% were male, and 74.1% were white. Among all participants, when asked if they would use a SIF, 63.0% answered "Yes", 31.5% answered "No", and 5.6% were unsure. Among the 31 participants reporting injection drug use in the last six months, 27 (87.1%) reported willingness to use a SIF; 15 of the 19 (78.9%) who injected less than daily reported willingness, while all 12 (100.0%) of the participants who injected daily reported willingness. Compared to participants who were unwilling or were unsure, participants willing to use a SIF were also more likely to have been homeless in the last six months, have accidentally overdosed, have used heroin, have used fentanyl non-medically, and typically use prescription opioids alone. CONCLUSIONS: Among young adults who use prescription opioids non-medically and inject drugs or are at risk of initiating injection drug use, more than six in ten reported willingness to use a SIF. Established risk factors for overdose, including homelessness, history of overdose, daily injection drug use, heroin use, and fentanyl misuse, were associated with higher SIF acceptability, indicating that young people at the highest risk of overdose might ultimately be the same individuals to use the facility. Supervised injection facilities merit consideration to reduce overdose mortality in the USA121019+ field[33]: Not in File?0XBraham, M.Y. Jedidi, M. Chkirbene, Y. Hmila, I. ElKhal, M.C. Souguir, M.K. Ben Dhiab, M.2017HCaregiver-fabricated illness in a child: a case report of three siblings39-42Journal of Forensic Nursing131case CASE REPORT Case-report child CHILDREN CHLORALOSE CLINICAL Clinical presentation DEATH ILLNESS IS LEGAL MEDICOLEGAL MORBIDITY MORTALITY PAEDIATRIC siblings SYMPTOMS TREATMENT Tunisia WHO1/2017Caregiver-fabricated illness in a child is a form of child maltreatment caused by a caregiver inducing a child's illness, leading to unnecessary and potentially harmful medical procedures and treatments. This condition can result in significant morbidity and mortality. We present the case of three siblings in Tunisia who were poisoned with chloralose by their own mother. The symptoms that the children presented with led to misdiagnoses, which resulted in the death of two of the children. Characteristics of the clinical presentation are articulated, followed by a discussion of the legal measures that apply to the offender and the role of physicians, nurses, and medicolegal experts involved in such a complex medical situation121048. field[33]: Not in FileB?1Brass, D.M. Palmer, S.M.20175Models of toxicity of diacetyl and alternative diones Toxicology,online early: doi: 10.1016/j.tox.2017.02.011not published, 01 Mar 17AIRWAY As chemical CONCENTRATIONS DIACETYL evidence EXPOSURE FOOD IMPAIRMENT Ingredient IS Long term Long-term LUNG LUNG FUNCTION MODEL Observation Obstructive OCCUPATIONAL ORGANIC REVIEW safe STUDY Testing Toxicities TOXICITY use vapor workers workplace 2/21/2017Diacetyl (DA; 2,3-butanedione), with the chemical formula (CH3CO)2 is a volatile organic compound with a deep yellow color and a strong buttery flavor and aroma. These properties have made DA a particularly useful and common food flavoring ingredient. However, because of this increased occupational use, workers can be exposed to high vapor concentrations in the workplace. Despite being listed by the USFDA to be 'generally regarded as safe' (GRAS), multiple lines of evidence suggest that exposure to high concentrations of DA vapor causes long-term impairments in lung function with lung function testing indicating evidence of either restrictive or obstructive airway narrowing in affected individuals. A growing number of pre-clinical studies have now addressed the short and long-term toxicity associated with DA exposure providing further insight into the toxicity of DA and related diones. This review summarizes these observations121130+ field[33]: Not in FileU?2/Bressman, M. Repplinger, D. Slater, W. Patt, M.2017mElectrophysiologic similarities of overdose between digoxin and bufadienolides found in a Chinese aphrodisiac76-78Journal of Arrhythmia331aphrodisiac APHRODISIACS As case CASE REPORT case reports Case-report CHINESE DEATH DIGOXIN HERBAL MEDICINE Medicine medicines OVERDOSE STEROID TOAD VENOM toxic Toxicities TOXICITY TREATMENT use Venom2/2017Classically derived from toad venom, bufadienolides are a group of cardioactive steroids with properties similar to digoxin. Some traditional Chinese medications, including several aphrodisiacs, contain bufadienolides. Owing to their physiologic similarities to digoxin, bufadienolides have been shown to produce a toxic profile similar to that of digoxin and there have been multiple case reports of the use of these aphrodisiacs resulting in death. This report will describe a case that illustrates the electrophysiologic similarities between bufadienolide toxicity and digoxin toxicity as well as the treatment of bufadienolide toxicity121037+ field[33]: Not in FileB?3"Brtalik, D. Stopyra, J. Hannum, J.2017bIntravenous poison hemlock injection resulting in prolonged respiratory failure and encephalopathyJournal of Medical Toxicology,online early: doi: 10.1007/s13181-017-0601-0not published, 28 Feb 17kALKALOIDS ARREST As CARDIAC CARDIAC ARREST CARDIOPULMONARY CARDIOPULMONARY ARREST case CASE REPORT case reports Case-report CIRCULATION DATA Emergencies emergency EMERGENCY DEPARTMENT ENCEPHALOPATHY FAILURE HEMLOCK Injecting INJECTION INTRAVENOUS INTRAVENOUS INJECTION IS MALE PATIENT PLANT Poison POISONING RESPIRATORY RESPIRATORY FAILURE Toxicities TOXICITY WHO2/6/2017.BACKGROUND: Poison hemlock (Conium maculatum) is a common plant with a significant toxicity. Data on this toxicity is sparse as there have been few case reports and never a documented poisoning after intravenous injection. OBJECTIVES: We present a case of intravenous poison hemlock injection encountered in the emergency department. CASE REPORT: We describe a 30-year-old male who presented to the emergency department after a brief cardiac arrest after injecting poison hemlock. The patient had return of spontaneous circulation in the emergency department but had prolonged muscular weakness and encephalopathy later requiring tracheostomy. CONCLUSION: Intravenous injection of poison hemlock alkaloids can result in significant toxicity, including cardiopulmonary arrest, prolonged weakness, and encephalopathy120900+ field[33]: Not in File?4[Buck Louis, G.M. Smarr, M.M. Sundaram, R. Steuerwald, A.J. Sapra, K.J. Lu, Z. Parsons, P.J.2017ILow-level environmental metals and metalloids and incident pregnancy loss68-74Reproductive Toxicology69ARSENIC BLOOD CADMIUM CONCENTRATIONS ENVIRONMENTAL Environmental exposure evidence EXPOSURE FEMALE HAZARD Incidence IS LEAD low-level MALE MERCURY METALS MODEL NO PREGNANCY reprotoxicity RISK STUDY2/2/2017Environmental exposure to metals and metalloids is associated with pregnancy loss in some but not all studies. We assessed arsenic, cadmium, mercury, and lead concentrations in 501 couples upon trying for pregnancy and followed them throughout pregnancy to estimate the risk of incident pregnancy loss. Using Cox proportional hazard models, we estimated hazard ratios (HR) and 95% confidence intervals (CIs) for pregnancy loss after covariate adjustment for each partner modeled individually then we jointly modeled both partners' concentrations. Incidence of pregnancy loss was 28%. In individual partner models, the highest adjusted HRs were observed for female and male blood cadmium (HR=1.08; CI 0.81, 1.44; HR=1.09; 95% CI 0.84, 1.41, respectively). In couple based models, neither partner's blood cadmium concentrations were associated with loss (HR=1.01; 95% CI 0.75, 1.37; HR=0.92; CI 0.68, 1.25, respectively). We observed no evidence of a significant relation between metal(loids) at environmentally relevant concentrations and pregnancy loss1209210 field[33]: Not in File?5Bunchorntavakul, C. Reddy, K.R.2017!Drug Hepatotoxicity: newer agents115-134Clinics in Liver Disease211agent ANTIBIOTIC Antibiotics ANTIBODIES ANTICOAGULANT anticoagulants ANTIDEPRESSANTS Antiepileptic ANTIEPILEPTICS Antipsychotic antipsychotics As BOSUTINIB case dabigatran DARUNAVIR DRUG Drug hepatotoxicity DULOXETINE Erlotinib FELBAMATE HEPATOTOXICITY IMATINIB Incidence INFLIXIMAB IS LAMOTRIGINE LEVETIRACETAM MONOCLONAL ANTIBODIES novel oral anticoagulants ORAL PONATINIB rivaroxaban SUNITINIB VENLAFAXINE2017Idiosyncratic hepatotoxicity is one of the most common reasons for an approved drug being restricted. This article focuses on hepatotoxicity of selected and recently introduced agents, such as, tyrosine kinase inhibitors, monoclonal antibodies, novel oral anticoagulants, newer antiplatelets, antibiotics, anti-diabetics, anti-epileptics, anti-depressants, anti-psychotics and anti-retrovirals. Overall, the incidence of clinically relevant hepatotoxicity from newer agents seems to be lower than that of the older agents. Nevertheless, cases of severe hepatotoxicity have been reported due to some of these newer agents, including, trastuzumab, ipilimumab, infliximab, imatinib, bosutinib, dasatinib, gefitinib, erlotinib, sunitinib, ponatinib, lapatinib, vemurafenib, dabigatran, rivaroxaban, felbamate, lamotrigine, levetiracetam, venlafaxine, duloxetine, darunavir, and maraviroc. Copyright © 2016 Elsevier Inc120822+ field[33]: Not in Fileg?64Burgos García, A. Froilán Torres, C. Tavecchia, M.2017&Endoscopic removal of a hashish packet235+Revista Espanola de Enfermedades Digestivas1093Abdominal Pain As body packers CANNABIS DRUG hashish HI HOSPITAL Illicit drug INGESTION IS LETTER MALE OVERDOSE pain REMOVAL RISK 2/27/2017121110/ field[33]: Not in File?7&Burke, W.J. Hoegg, U.R. Phillips, R.E.1973?Systemic fluoride poisoning resulting from a fluoride skin burn39-412Journal of Occupational and Environmental Medicine151CACID Burn DERMAL FLUORIDE HYDROFLUORIC ACID POISONING SKIN SYSTEMIC1973120843d Not in File ?8,Byard, R.W. Musgrave, I. Maker, G. Bunce, M.2017?What risks do herbal products pose to the Australian community?86-90Medical Journal of Australia2062yACUTE ANIMAL As ASARUM Australia Awareness chemical CHEMICALS CONCENTRATIONS Content DEATH DISEASE DRUG drugs effectiveness EPHEDRA FAILURE GINGER HEALTH Heavy metal HEAVY METALS HEPATIC HERBAL MEDICINE ILLNESS Ingredient INTERACTION IS Medicine medicines METALS MONITORING ORGANIC PLANT plants PUBLIC quality Regulation RENAL RENAL FAILURE RISK safe SPECIES toxic toxin TOXINS2/6/20170Traditional herbal products are widely used in Australia to treat a broad range of conditions and diseases. It is popularly believed that these products are safer than prescribed drugs. While many may be safe, it is worrying that the specific effects and harmful interactions of a number of their components with prescription medications is not well understood. Some traditional herbal preparations contain heavy metals and toxic chemicals, as well as naturally occurring organic toxins. The effects of these substances can be dire, including acute hepatic and renal failure, exacerbation of pre-existing conditions and diseases, and even death. The content and quality of herbal preparations are not tightly controlled, with some ingredients either not listed or their concentrations recorded inaccurately on websites or labels. Herbal products may also include illegal ingredients, such as ephedra, Asarum europaeum (European wild ginger) and endangered animal species (eg, snow leopard). An additional problem is augmentation with prescription medications to enhance the apparent effectiveness of a preparation. Toxic substances may also be deliberately or inadvertently added: less expensive, more harmful plants may be substituted for more expensive ingredients, and processing may not be adequate. The lack of regulation and monitoring of traditional herbal preparations in Australia and other Western countries means that their contribution to illness and death is unknown. We need to raise awareness of these problems with health care practitioners and with the general public120711% field[33]: Not in File ?9Cabeza, L. Ortiz, R. Prados, J. Delgado, Á.V. Martín-Villena, M.J. Clares, B. Perazzoli, G. Entrena, J.M. Melguizo, C. Arias, J.L.2017Improved antitumor activity and reduced toxicity of doxorubicin encapsulated in poly(epsilon-caprolactone) nanoparticles in lung and breast cancer treatment: an in vitro and in vivo study24-34+European Journal of Pharmaceutical Sciences102eAs BLOOD BREAST CANCER CANCER CELL CELL PROLIFERATION CYTOTOXICITY DOXORUBICIN DRUG HUMAN Humans IN VITRO IN VIVO Incidence Inhibition LUNG lung cancer method MICE MODEL Modified mouse NANOPARTICLES NO NPS Population Reduction SOLVENT STUDY SURVIVAL TISSUE Tissue damage Toxicities TOXICITY Toxicity study TRANSPORT TREATMENT tumor Volume WEIGHT Weight Loss 2/17/2017IPoly(epsilon-caprolactone) (PCL) nanoparticles (NPs) offer many possibilities for drug transport because of their good physicochemical properties and biocompatibility. Doxorubicin-loaded PCL NPs have been synthesized to try to reduce the toxicity of doxorubicin (DOX) for healthy tissues and enhance its antitumor effect in two tumor models, breast and lung cancer, which have a high incidence in the global population. PCL NPs were synthesized using a modified nanoprecipitation solvent evaporation method. The in vitro toxicity of PCL NPs was evaluated in breast and lung cancer cell lines from both humans and mice, as was the inhibition of cell proliferation and cell uptake of DOX-loaded PCL NPs compared to free DOX. Breast and lung cancer xenografts were used to study the in vivo antitumor effect of DOX-loaded NPs. Moreover, healthy mice were used for in vivo toxicity studies including weight loss, blood toxicity and tissue damage. The results showed good biocompatibility of PCL NPs in vitro, as well as a significant increase in the cytotoxicity and cell uptake of the drug-loaded in PCL NPs, which induced almost a 98% decrease of the IC50 (E0771 breast cancer cells). Likewise, DOX-loaded PCL NPs led to a greater reduction in tumor volume ( approximately 36%) in studies with C57BL/6 mice compared to free DOX in both lung and breast tumor xenograft models. Nevertheless, no differences were found in terms of mouse weight. Only in the lung cancer model were significant differences in mice survival observed. In addition, DOX-loaded PCL NPs were able to reduce myocardial and blood toxicity in mice compared to free DOX. Our results showed that DOX-loaded PCL NPs were biocompatible, enhanced the antitumor effect of DOX and reduced its toxicity, suggesting that they may have an important potential application in lung and breast cancer treatments121002, field[33]: Not in File }?:oCallejo, A. Durochat, A. Bressieux, S. Saleur, A. Chabbert, C. Domènech Juan, I. Llorens, J. Gaboyard-Niay, S.2017VDose-dependent cochlear and vestibular toxicity of trans-tympanic cisplatin in the rat1-9Neurotoxicology60analysis As Body Weight CELL CISPLATIN COMPARISON CONCENTRATIONS EAR EXPOSURE HAIR IN VIVO lethality MICE MODEL MORBIDITY NEUROTOXICITY NO OTOTOXICITY RAT rats RESEARCH Route safe Sex SPECIES STUDY SYSTEMIC TEST Toxicities TOXICITY TREATMENT WEIGHT Weight Loss 2/14/2017IIn vivo studies are needed to study cisplatin ototoxicity and to evaluate candidate protective treatments. Rats and mice are the preferred species for toxicological and pharmacological pre-clinical research, but systemic administration of cisplatin causes high morbidity in these species. We hypothesized that trans-tympanic administration of cisplatin would provide a good model for studying its auditory and vestibular toxicity in the rat. Cisplatin was administered by the trans-tympanic route in one ear (50mul, 0.5-2mg/ml) of rats of both sexes and two different strains. Cochlear toxicity was corroborated by histological means. Vestibular toxicity was demonstrated by behavioral and histological analysis. Cisplatin concentrations were assessed in inner ear after trans-tympanic and i.v. administration. In all experiments, no lethality and only scant body weight loss were recorded. Cisplatin caused dose-dependent cochlear toxicity, as demonstrated by hair cell counts in the apical and middle turns of the cochlea, and vestibular toxicity, as demonstrated by behavioral analysis and hair cell counts in utricles. High concentrations of cisplatin were found in the inner ear after trans-tympanic administration. In comparison, i.v. administration resulted in lower inner ear concentrations. We conclude that trans-tympanic administration provides an easy, reproducible and safe model to study the cochlear and vestibular toxicity of cisplatin in the rat. This route of exposure may be useful to address particular questions on cisplatin induced ototoxicity and to test candidate protective treatments121078- field[33]: Not in File ?;Cantoral, A. Batis, C. Basu, N.2017National estimation of seafood consumption in Mexico: implications for exposure to methylmercury and polyunsaturated fatty acids289-296 Chemosphere174)ACID Age Aged ANCHOVIES As Consumption DATA DIETARY Dietary exposure ENVIRONMENTAL EXPOSURE Fatty acids Guidelines HEALTH INFORMATION Intake IS MERCURY method methods METHYLMERCURY Mexico ORGANIC PUBLIC PUBLIC HEALTH Seafood Sex SHRIMP Socioeconomic status Source SPECIES STATUS STUDY SURVEY toxic 1/26/2017RBACKGROUND: Seafood is a good source of Omega-3 polyunsaturated fatty acids (omega3-PUFA) but also contains the toxic contaminant methylmercury (MeHg). National estimates of exposure to both compounds through seafood intake in Mexico are not known. The objective of the current study was to describe national seafood consumption habits and to estimate seafood-based exposure to omega3-PUFAs and MeHg. METHODS: We analyzed data from a 24-h dietary recall extracted from the 2012 National Health and Nutrition Survey of Mexico (n = 10,096 subjects aged 1y and older). National per capita seafood intake as well as information on age, sex, socioeconomic status, and geographic region was obtained. The contribution of each seafood item to the total MeHg exposure was estimated, as was the balance between estimated exposures to omega3-PUFAs and MeHg. RESULTS: A mean daily seafood intake of 10 g/day was estimated. The top species consumed in decreasing order were: canned tuna, sunfish, shrimp, mullet, carp and schoolshark (constituted 60% of seafood intake). Canned tuna and schoolshark contributed 75% of the population's estimated exposure to MeHg. The best balance of population-level exposures to omega3-PUFAs and MeHg was found in salmon, sardine, trout and anchovies. CONCLUSION: Environmental dietary exposure to MeHg is a public health concern and thus a good understanding of seafood consumption is needed to create national consumption guidelines. The current study provides nationally-representative data in Mexico from which decisions can be made (e.g., UN Minamata Convention) and future studies conducted1208633 field[33]: Not in FileB?<Cantrell, F.L. McIntyre, I.M.2017<An alarming increase in local pentobarbital-related suicidesClinical Toxicology0online early: doi: 10.1080/15563650.2017.1290256not published, 03 Mar 17ANTIEMETIC BLOOD blood concentration case CONCENTRATIONS dose ETHANOL EXPOSURE HI HOME INGESTION INTRAVENOUS IS lethal LETTER Mexico PENTOBARBITAL PERIPHERAL REVIEW Route SUICIDE TOXICOLOGY toxin US Veterinary 2/13/2017121148/ field[33]: Not in File c?=PCappozzo, J. Jackson, L. Lee, H.J. Zhou, W. Al-Taher, F. Zweigenbaum, J. Ryu, D.2017?Occurrence of ochratoxin A in infant foods in the United States251-256Journal of Food Protection802_ADULT AGRICULTURAL Baby foods Body Weight CHILDREN CONCENTRATIONS DIET EXPOSURE FOOD HUMAN Incidence INFANT Infants IS LEVELS Liquid chromatography tandem mass spectrometry Liquid chromatography-tandem mass spectrometry MASS SPECTROMETRY MILK MONITORING NO Occurrence PAEDIATRIC Regulatory SPECTROMETRY STUDY SURVEILLANCE Toxicant UNITED STATES WEIGHT2/2017Ochratoxin A (OTA) is a possible human carcinogen and occurs frequently in cereal grain, soy, and other agricultural commodities. Infants and young children may be more susceptible to contaminants than adults because of their lower body weight, higher metabolic rate, reduced ability to detoxify food toxicants, and more restricted diet. The purpose of this study was to investigate the occurrence and levels of OTA in infant formula and infant cereal products available in the U.S. market. In the present study, 98 powdered infant formula (milk- and soy-based) samples and 155 infant cereal (barley-, rice-, oat-, wheat-, and mixed grain-based) products were collected from different retail locations in the United States over a 2-year period. OTA levels were determined by liquid chromatography-tandem mass spectrometry. Although OTA was not detected in any of the infant formula samples, 47 (30%) of 155 infant cereals were contaminated with OTA in the range of 0.6 to 22.1 ng/g. At present, there is no regulatory limit for OTA in the United States. However, all of the positive samples were above the maximum level set by the European Commission (0.5 ng/g) for OTA in baby foods. OTA was detected in all types of infant cereals, but the highest incidence and concentrations were found in oat-based infant cereals (59%), followed by mixed grain cereals (34%). Increased surveillance and monitoring of OTA levels in grains used in infant foods may be needed to reduce exposure of infants and young children to OTA from cereal products121046. field[33]: Not in FileB?>Caulkins, J.P.20178Recognizing and regulating cannabis as a temptation good$International Journal of Drug Policy/online early: doi: 10.1016/j.drugpo.2017.01.012not published, 01 Mar 17ACUTE ALCOHOL As Behavior CANNABIS Consumption CRIME family harm Harms HEALTH INTOXICATION IS legalization MISUSE MODEL PUBLIC PUBLIC HEALTH SOCIAL Substance use substance use disorder use WHO 2/10/2017The U.S. appears to be on a path toward legalizing cannabis on the alcohol model, which is to say allowing for-profit corporations to produce, sell, and promote its use. Even after national legalization, it will take decades to observe the full effects on industry structure and behavior, or on use and misuse. However, we should not be surprised if after markets have matured and consumption patterns stabilized, legalization increases acute cannabis intoxication in the U.S. by 40 billion hours per year. This increase in use will be the most important cannabis-specific effect of legalization. The bulk of it will be consumption by daily and near-daily users, and it is possible that roughly half will be by people who meet the medical criteria for substance use disorder. Much resulting harms will be borne by the users, and their families, and the harms are not primarily "medical", at least not in the narrow sense. Hence, legalization replaces the current problems of crime and black markets not so much with a medical or public health problem, but rather with a problem of potentially excessive consumption of a "temptation good" whose acute effects are performance degrading, not performance-enhancing. As legalization removes formal social controls, it might be prudent for society to develop stronger informal social norms - akin to "friends don't let friends drive drunk" - to protect the public and more importantly the users themselves from the performance degradation of bouts of nearly perpetual intoxication121023. field[33]: Not in File aB??JChan, M.C. Bautista, E. Alvarado-Cruz, I. Quintanilla-Vega, B. Segovia, J.2017Inorganic mercury prevents the differentiation of SH-SY5Y cells: amyloid precursor protein, microtubule associated proteins and ROS as potential targets1Journal of Trace Elements in Medicine and early: doi: 10.1016/j.jtemb.2017.02.002not published, 01 Mar 17ACID As Attention BRAIN CELL DATA DENTAL DENTAL AMALGAM Development Differentiation EXPOSURE GOLD Gold mining Hg IMPAIRMENT INORGANIC Inorganic mercury IS LEVELS MERCURY mining NITRIC OXIDE NO OXYGEN Pathway PRECURSOR PROTEIN proteins ROS Seafood SPECIES STUDY Toxicities TOXICITY2/6/2017Exposure to mercury (Hg) occurs through different pathways and forms including methylmecury (MeHg) from seafood and rice, ethylmercury (EtHg), and elemental Hg (Hg0) from dental amalgams and artisanal gold mining. Once in the brain all these forms are transformed to inorganic Hg (I-Hg), where it bioaccumulates and remains for long periods. Hg is a well-known neurotoxicant, with its most damaging effects reported during brain development, when cellular key events, such as cell differentiation take place. A considerable number of studies report an impairment of neuronal differentiation due to MeHg exposure, however the effects of I-Hg, an important form of Hg found in brain, have received less attention. In this study, we decided to examine the effects of I-Hg exposure (5, 10 and 20muM) on the differentiation of SH-SY5Y cells induced by retinoic acid (RA, 10muM). We observed extension of neuritic processes and increased expression of neuronal markers (MAP2, tubulin-betaIII, and Tau) after RA stimulation, all these effects were decreased by the co-exposure to I-Hg. Interestingly, I-Hg increased the levels of reactive oxygen species (ROS) and nitric oxide (NO) accompanied with increased levels of inducible nitric oxide synthase (iNOS) and, dimethylarginine dimethylaminohydrolase 1 (DDHA1). Remarkably I-Hg decreased levels of nitric oxide synthase neuronal (nNOS). Moreover I-Hg reduced the levels of tyrosine hydroxylase (TH) and amyloid precursor protein (APP) a protein recently involved in neuronal differentiation. These data suggest that the exposure to I-Hg impairs cell differentiation, and point to new potential targets of Hg toxicity such as APP and NO signaling121065- field[33]: Not in File?@{Chang, C.-C. Hsiao, I.-T. Huang, S.-H. Lui, C.-C. Yen, T.-C. Chang, W.-N. Huang, C.-W. Hsieh, C.-J. Chang, Y.-Y. Lin, K.-J.201518F-FP-(+)-DTBZ positron emission tomography detection of monoaminergic deficient network in patients with carbon monoxide related parkinsonism845-e60European Journal of Neurology225Age analysis As ASSESSMENT Atrophy carbon CARBON MONOXIDE CO cognitive COMPARISON DETECTION Diffusion tensor imaging DISEASE Imaging INTOXICATION IS MAGNETIC RESONANCE method methods MODEL NEUROLOGICAL NEUROPSYCHIATRIC NEUROTOXICITY NEUROTRANSMITTER Parkinson's disease PARKINSONISM PATHOPHYSIOLOGY PATIENT PET positron emission tomography PUTAMEN SCALE SEVERITY STATISTICS STUDY Thalamus TOMOGRAPHY Toxicities TOXICITY Volume2015Background and purpose: Although parkinsonism after carbon monoxide (CO) intoxication is well known, neurotransmitter deficient networks that are responsible for the severity of parkinsonism have rarely been systemically evaluated. Methods: Eighteen patients with CO-related parkinsonism and nine age- and sex-matched controls were enrolled for detailed neurological examinations, three-dimensional T1-weighted images, diffusion tensor imaging and 18F-9-fluoropropyl-(+)-dihydrotetrabenzazine (18F-FP-(+)-DTBZ) positron emission tomography (PET). The structural analysis included voxel-based morphometry to assess grey matter atrophy and tract-based spatial statistics related to white matter involvement. For presynaptic monoaminergic assessment, volume of interest analysis in six subcortical regions and non-parametric voxel-wise comparison were performed on PET images with estimation of registration parameters from magnetic resonance images. All the imaging modalities were compared between the patients and controls. For the patients, a regression model for correlation with cognitive behaviour and Unified Parkinson's Disease Rating Scale (UPDRS) score was used. Results: In the patients, monoaminergic deficit networks were found in the caudate, anterior putamen, anterior insular, thalamus and anterior cingulate cortex. The UPDRS revealed significant correlations with the prefrontal white matter fractional anisotropy values and with the 18F-FP-(+)-DTBZ uptake values in the caudate nucleus, insular, medial prefrontal and dorsomedial thalamus. The neuropsychiatric inventory score correlated with the 18F-FP-(+)-DTBZ uptake values in the anterior cingulate cortex and dorsolateral prefrontal cortex. Conclusions: Our study demonstrated monoaminergic deficits and white matter damage networks in CO-related parkinsonism that determined the severity of parkinsonism or behaviour changes. As the substantia nigra was spared, the monoaminergic topography of involvement suggests a different pathophysiology in CO-related parkinsonism. European Journal of Neurology Copyright © 2015 European Academy of Neurology225 May 2015 10.1111/ene.12672 Original Article Original Articles © 2015 EAN120712# field[33]: Not in File%?A Chang, J.O. Choi, J.W. Hwang, Y.2016yA case of severe corrosive esophagitis, gastritis, and liver necrosis caused by ingestion of methyl ethyl ketone peroxide256-261,Clinical and Experimental Emergency Medicine34*ACIDOSIS As case Corrosive esophagitis CORROSIVES FAILURE FATAL GASTRITIS GASTROINTESTINAL HEPATOTOXICITY ingested INGESTION IS ISCHEMIA LIVER LIVER NECROSIS Man METABOLIC ACIDOSIS METHYL ETHYL KETONE METHYL ETHYL KETONE PEROXIDE NECROSIS OXYGEN PATIENT Peroxide POISONING Release RESUSCITATION WHO12/2016The plastic hardener methyl ethyl ketone peroxide is unstable peroxide that releases free oxygen radicals. Ingestion of this compound induces widespread liver necrosis, severe metabolic acidosis, corrosive esophagitis and gastritis, that is often fatal. A 49-year-old man unintentionally ingested approximately 100 mL (55%) of this compound in solution, which was purchased as plastic hardener. Despite resuscitation, he died about 11 hours after admission. We report a patient with poisoning due to methyl ethyl ketone peroxide who presented with corrosive esophagitis and gastritis, gastrointestinal bleeding, and developed ischemia of the bowel and necrosis of the liver and died of severe metabolic acidosis and multiorgan failure120867& field[33]: Not in File?BGChang, K.-C. Wang, J.-D. Saxon, A. Matthews, A.G. Woody, G. Hser, Y.-I.2017zCauses of death and expected years of life lost among treated opioid-dependent individuals in the United States and Taiwan1-6$International Journal of Drug Policy43Age Cohort DATA DEATH Deaths Intervention strategy method methods MORTALITY OPIOID Opioids OVERDOSE Population Randomized trial RISK standardized mortality ratios STUDY SUICIDE SURVIVAL Taiwan TREATMENT TRIAL UNITED STATES2/1/2017AIMS: This study compared the cause-specific standardized mortality ratios (SMRs) and expected years of life lost (EYLL) among opioid-dependent individuals in the United States and Taiwan. METHODS: Survival data came from two cohorts followed until 2014: The U.S. data were based on a randomized trial of 1267 opioid-dependent participants enrolled between 2006 and 2009; the Taiwan data were from a study of 983 individuals that began in 2006, when opioid agonist treatment (OAT) was implemented in Taiwan. SMRs were calculated for each national cohort and compared. Kaplan-Meier estimation was performed on the survival data, then lifespans were extrapolated to 70 years (840 months) to estimate life expectancy using a semi-parametric method. EYLLs for both cohorts were estimated by subtracting their life expectancies from the age- and gender-matched referents within the general population of their respective country. RESULTS: Compared with age- and gender-matched referents, the SMRs were 3.2 for the U.S. sample and 7.8 for the Taiwan sample; the EYLLs were 7.7 and 16.4 years, respectively. Half of decedents died of unnatural causes in both cohorts; overdose deaths predominated in the U.S. and suicide in Taiwan. CONCLUSIONS: Our study identified differences by country in EYLL and causes of deaths. These findings suggest that intervention strategies to reduce mortality risk by overdose (particularly in the U.S.) and suicide (particularly in Taiwan) are urgently needed in these countries120713. field[33]: Not in File B?CCharlton, R.A. McGrogan, A. Snowball, J. Yates, L.M. Wood, A. Clayton-Smith, J. Smithson, W.H. Richardson, J.L. McHugh, N. Thomas, S.H.L. Baker, G.A. Bromley, R.2017Sensitivity of the UK Clinical Practice Research Datalink to detect neurodevelopmental effects of medicine exposure in utero: comparative analysis of an antiepileptic drug-exposed cohort Drug Safety,online early: doi: 10.1007/s40264-017-0506-5not published, 28 Feb 17Age analysis ANTICONVULSANT anticonvulsants Antiepileptic ASSESSMENT CHILDREN CLINICAL Cohort Cohort studies Cohort study COMPARATIVE COMPARISON DATA DIAGNOSIS DRUG EPILEPSY EXPOSURE IN UTERO IS Medicine method methods Monotherapy Neurodevelopment Odds Ratio outcome P PREGNANCY PRENATAL prevalence prospective cohort study prospective study RESEARCH RISK Sensitivity STUDY UK VALPROATE WOMEN 2/10/2017eINTRODUCTION: Electronic healthcare data have several advantages over prospective observational studies, but the sensitivity of data on neurodevelopmental outcomes and its comparability with data generated through other methodologies is unknown. OBJECTIVES: The objectives of this study were to determine whether data from the UK Clinical Practice Research Datalink (CPRD) produces similar risk estimates to a prospective cohort study in relation to the risk of neurodevelopmental disorders (NDDs) following prenatal antiepileptic drug (AED) exposure. METHODS: A cohort of mother-child pairs of women with epilepsy (WWE) was identified in the CPRD and matched to a cohort without epilepsy. The study period ran from 1 January 2000 to 31 March 2007 and children were required to be in the CPRD at age 6 years. AED exposure during pregnancy was determined from prescription data and children with an NDD diagnosis by 6 years were identified from Read clinical codes. The prevalence and risk of NDDs was calculated for mother-child pairs in WWE stratified by AED regimen and for those without epilepsy. Comparisons were made with the results of the prospective Liverpool and Manchester Neurodevelopment Group study which completed assessment on 201 WWE and 214 without epilepsy at age 6 years. RESULTS: In the CPRD, 1018 mother-child pairs to WWE and 6048 to women without epilepsy were identified. The CPRD identified a lower prevalence of NDDs than the prospective study. In both studies, NDDs were more frequently reported in children of WWE than women without epilepsy, although the CPRD risk estimate was lower (2.16 vs. 0.96%, p < 0.001 and 7.46 vs. 1.87%, p = 0.0128). NDD prevalence differed across AED regimens but the CPRD data did not replicate the significantly higher risk of NDDs following in utero monotherapy valproate exposure (adjusted odds ratio [ORadj] 2.02, 95% confidence interval [CI] 0.52-7.86) observed in the prospective study (ORadj 6.05, 95% CI 1.65-24.53). CONCLUSION: It was possible to identify NDDs in the CPRD; however, the CPRD appears to under-record these outcomes. Larger studies are required to investigate further120873+ field[33]: Not in File 7B?D*Chen, C.-Y. Lin, P. Tsai, M.-H. Lee, H.-L.2017Targeted lipidomics profiling of acute arsenic exposure in mice serum by on-line solid-phase extraction stable-isotope dilution liquid chromatography-tandem mass spectrometryArchives of Toxicology,online early: doi: 10.1007/s00204-017-1937-6not published, 01 Mar 17ACID ACUTE analysis ANALYTICAL Arachidonic acid ARSENIC biological Biological samples Characterization DETECTION Eicosanoids EXPOSURE EXTRACTION Fatty acids IS Knowledge LEVELS Limit of Detection LIPID Liquid chromatography tandem mass spectrometry Liquid chromatography-tandem mass spectrometry MASS SPECTROMETRY METABOLISM method MICE mouse ON-LINE PRECURSOR quantification SERUM simple sample preparation Solid phase extraction Solid-phase extraction SPECTROMETRY STUDY Tandem Mass Spectrometry Vehicle Volume 2/16/2017Lipidomics is the area of study dedicated to the comprehensive analysis and characterization of the functions and metabolism of lipids in biological samples. One of the most comprehensively studied classes of lipids is polyunsaturated fatty acids (PUFAs). Eicosanoids are a series of bioactive lipid mediators that are metabolized from PUFAs and generated majorly from the precursor arachidonic acid. This study identified the profiles of target eicosanoids after acute exposure to arsenic. The principle objective was to determine and validate 10 eicosanoids in mouse serum using on-line solid-phase extraction integrated with liquid chromatography-electrospray tandem mass spectrometry. Intra-day and inter-day repeatability was 82.4-119.2 and 86.7-124.4%, respectively. The limit of detection and limit of quantification were from 0.003 to 0.288 ng/mL and from 0.009 to 0.962 ng/mL, respectively. The levels of 7 of the 10 eicosanoids-namely 8-isoPGF2alpha, PGF2alpha, PGE2, 13(s)-HODE, 15(s)-HETE, 12(s)-HETE, and 5(s)-HETE-in mouse serum significantly and dose-dependently increased after arsenic exposure compared with the levels in the vehicle control group. To our knowledge, this is the first study to quantify eicosanoids in mouse serum. This approach provides simple sample preparation, small sample volumes, and a precise and accurate method for determining changes in the profile of these eicosanoids in mouse serum after acute exposure to arsenic120946, field[33]: Not in File B?EN7Chen, C. Bu, W. Ding, H. Li, Q. Wang, D. Bi, H. Guo, D.2017Cytotoxic effect of zinc oxide nanoparticles on murine photoreceptor cells via potassium channel block and Na+ /K+ -ATPase inhibitionCell Proliferation$online early: doi: 10.1111/cpr.12339not published, 01 Mar 17-ASSAY CELL CYTOTOXICITY determination Inhibition IS LACTATE LEVELS Measurement MECHANISM MEMBRANE method methods Mitochondrial membrane potential MONITORING NANOPARTICLES OXIDATIVE STRESS OXYGEN POTASSIUM PROTEIN Release ROS SPECIES STRESS STUDY toxic toxic effects Toxicities TOXICITY ZINC ZINC OXIDE 2/19/2017OBJECTIVE: Zinc oxide (ZnO) nanoparticles can exhibit toxicity towards organisms and oxidative stress is often hypothesized to be one of the most important factors. Nevertheless, the detailed mechanism of toxicity-induced by ZnO nanoparticles has not been completely addressed. The present study aimed to investigate the toxic effects of ZnO nanoparticles on the expression and activity of Na+ /K+ -ATPase and on potassium channel block. MATERIALS AND METHODS: In the present study, we explored the cytotoxic effect of ZnO nanoparticles on murine photoreceptor cells using lactate dehydrogenase (LDH) release assay, reactive oxygen species (ROS) determination, mitochondrial membrane potential (Deltaphim) measurement, delayed rectifier potassium current recordings and Na+ /K+ -ATPase expression and activity monitoring. RESULTS: The results indicated that ZnO nanoparticles could increase the LDH release in medium, aggravate the ROS level within cells, collapse the Deltaphim, block the delayed rectifier potassium current, and attenuate the expressions of Na+ /K+ -ATPase at both mRNA and protein levels and its activity, and thus exert cytotoxic effects on murine photoreceptor cells, finally damaging target cells. CONCLUSION: Our findings will facilitate the understanding of the mechanism involved in ZnO nanoparticle-induced cytotoxicity in murine photoreceptor cells via potassium channel block and Na+ /K+ -ATPase inhibition120959# field[33]: Not in File oB?FChen, H. Carter, K.E.2017Modeling potential occupational inhalation exposures and associated risks of toxic organics from chemical storage tanks used in hydraulic fracturing using AERMODEnvironmental Pollution/online early: doi: 10.1016/j.envpol.2017.02.008not published, 01 Mar 17ACUTE AIR AIR CONCENTRATION CANCER chemical CHEMICALS CHRONIC CONCENTRATIONS DATA Emission source Emissions EXPOSURE FORMALDEHYDE HEALTH Health risk Health risks hydraulic fracturing INHALATION Inhalation Exposure Measurement METHANOL OCCUPATIONAL ORGANIC RISK Source STUDY toxic UNIT 2/18/2017Various toxic chemicals used in hydraulic fracturing fluids may influence the inherent health risks associated with these operations. This study investigated the possible occupational inhalation exposures and potential risks related to the volatile organic compounds (VOCs) from chemical storage tanks and flowback pits used in hydraulic fracturing. Potential risks were evaluated based on radial distances between 5 m and 180 m from the wells for 23 contaminants with known inhalation reference concentration (RfC) or inhalation unit risks (IUR). Results show that chemicals used in 12.4% of the wells posed a potential acute non-cancer risks for exposure and 0.11% of the wells with may provide chronic non-cancer risks for exposure. Chemicals used in 7.5% of the wells were associated with potential acute cancer risks for exposure. Those chemicals used in 5.8% of the wells may be linked to chronic cancer risks for exposure. While eight organic compounds were associated with acute non-cancer risks for exposure (>1), methanol the major compound in the chemical storage tanks (1.00-45.49) in 7,282 hydraulic fracturing wells. Wells with chemicals additives containing formaldehyde exhibited both acute and chronic cancer risks for exposure with IUR greater than 10-6, suggesting formaldehyde was the dominant contributor to both types of risks for exposure in hydraulic fracturing. This study also found that due to other existing on-site emission sources of VOCs and the geographically compounded air concentrations from other surrounding wells, chemical emissions data from storage tanks and flowback pits used in this study were lower than reported concentrations from field measurements where higher occupational inhalation risks for exposure may be expected120984. field[33]: Not in File?GAChen, Z. Jin, Z. Xia, Y. Zhao, S. Xu, X. Papadimos, T.J. Wang, Q.2017The protective effect of lipid emulsion in preventing bupivacaine-induced mitochondrial injury and apoptosis of H9C2 cardiomyocytes430-436 Drug Delivery241Dapoptosis ARREST As ATP BUPIVACAINE CALCIUM CARDIAC CARDIAC ARREST CELL Content electron microscopy ENZYME INFORMATION Inhibition injuries Injury LIPID Lipid emulsion LIPID EMULSION THERAPY MECHANISM MEMBRANE MICROSCOPY MITOCHONDRIA Mitochondrial membrane potential MYOCARDIUM RESUSCITATION STUDY THERAPY Toxicities TOXICITY11/2017nLipid emulsion (LE) has been shown to be effective in the resuscitation of bupivacaine-induced cardiac arrest, but the precise mechanism of this action has not been fully elucidated. Pursuant to this lack of information on the mechanism in which LE protects the myocardium during bupivacaine-induced toxicity, we explored mitochondrial function and cell apoptosis. H9C2 cardiomyocytes were used in study. Cells were randomly divided in different groups and were cultivated 6 h, 12 h, and 24 h. The mitochondria were extracted and mitochondrial ATP content was measured, as was mitochondrial membrane potential, the concentration of calcium ion (Ca2+), and the activity of Ca2+-ATP enzyme (Ca2+-ATPase). Cells from groups Bup1000, LE group, and Bup1000LE were collected to determine cell viability, cell apoptosis, and electron microscopy scanning of mitochondrial ultrastructure (after 24 h). We found that LE can reverse the inhibition of the mitochondrial function induced by bupivacaine, regulate the concentration of calcium ion in mitochondria, resulting in the protection of myocardial cells from toxicity induced by bupivacaine120872/ field[33]: Not in File?H0Cheng, Y. Shan, Z. Zhou, J. Bu, Y. Li, P. Lu, S.2017nEffects of 4-nonylphenol in drinking water on the reproductive capacity of Japanese quails (Coturnix japonica)219-227 Chemosphere175Body Weight CONCENTRATIONS dose DRINKING WATER Environment ENVIRONMENTAL EXPOSURE FOOD Intake IS JAPANESE LESIONS Long term Long-term MALE NO NONYLPHENOL P PHENOL reprotoxicity STUDY SURVIVAL Time TREATMENT WATER WEIGHT2/8/20174-nonylphenol (4-NP), a major degradation product of Nonylphenol ethoxylates (NPEOs), is widespread in environment. In this study, the effects of long-term 4-NP exposure in drinking water on Japanese quails (Coturnix japonica) were investigated. A total of 45 quails were evenly divided into 15 groups and administrated with various doses (0.1 mug L-1, 1.0 mug L-1, 10 mug L-1 and 100 mug L-1, which reflected the environmental concentrations of 4-NP) of 4-NP in drinking water. The results showed that 4-NP in drinking water had no effect on quails' food intake, but significantly decreased the quails' body weights (P < 0.05) in a time- and dose-dependent manner. The egg fertilization rates were also significantly decreased (P < 0.05) in all treatment groups. Moreover, the hatchability was significantly reduced (P < 0.05) in 10 mug L-1 and 100 mug L-1 groups, and the 14 d survival rates of young quails were significantly decreased (P < 0.05) in 1.0 mug L-1, 10 mug L-1 and 100 mug L-1 groups. Damaged spermatogenesis in male quails was observed in all treatment groups. Therefore, administration of 4-NP in drinking water impaired the reproductive ability of Japanese quails, and led to pathological lesions in the male gonads1209643 field[33]: Not in File ?IiChernyak, Y.I. Merinova, A.P.2017QHSP70 (HSPA1) polymorphisms in former workers with chronic mercury vapor exposure77-85<International Journal of Occupational & Environmental Health3014Age analysis Association case CAUSTIC CHRONIC Development DIAGNOSIS DISEASE duration EXPOSURE family genetic HEALTH INTOXICATION MALE MECHANISM Mechanisms MERCURY mercury vapor method methods MODEL OCCUPATIONAL Occurrence Odds Ratio P PLANT plants POLYMORPHISM Regression Analysis RISK Time vapor WHO workers 2/21/2017^OBJECTIVES: To investigate 4 loci of 3 HSP70 genes in caustic soda production plant former workers, who have been exposed to metallic mercury vapors for a long time, and including numerous cases of chronic mercury intoxication (CMI). MATERIAL AND METHODS: Polymorphisms in HSP70 gene family members (HSP1A1 (+190G/C, rs1043618), HSPA1B (+1267A/G and +2074G/C, rs1061581) and HSP1AL (+2437T/C, rs2227956)) genes were studied among 120 male workers involved in caustic soda production by mercury electrolysis at 2 plants in Eastern Siberia. These subjects had been chronically exposed to metallic mercury vapors for > 5 years and divided into 3 groups based on the occurrence and time of the CMI diagnosis, or absence of this disease. The Group 1 consisted of individuals (N = 46), who had had contact with mercury but were not diagnosed with the CMI. The Group 2 included workers (N = 56), who were diagnosed with the CMI longer than 14 years ago. The Group 3 consisted of the subjects (N = 18), who had been diagnosed with the CMI 3-5 years ago. The logistic regression analysis was used for 3 genetic models with and without adjustment for age and duration of mercury vapor exposure. RESULTS: We found that genotypes capital ES, Cyrilliccapital ES, Cyrillic-HSPA1A (+190G/C) and GG-HSPA1B (+1267A/G) had a high predictive risk of the CMI development (adjusted odds ratio (ORadj) = 5.58, p = 0.026 and ORadj = 14.7, p = 0.0015, respectively). Twelve individuals with the CMI had a specific combination of capital ES, Cyrilliccapital ES, Cyrillic-HSPA1A (+190G/C) and GG-HSPA1B (+1267A/G) genotypes, which strongly associated with the diagnosis (ORadj = 12.3, p = 0.0285). Moreover, significant association with the CMI was also obtained for the haplotype G-C of 1267A/G and 190G/C polymorphisms (OR = 2.1, p = 0.018). CONCLUSIONS: The association of capital ES, Cyrilliccapital ES, Cyrillic-HSPA1A (+190G/C) and GG-HSPA1B (+1267A/G) genotypes and their combination for the CMI individuals suggests the role for HSPA1 genes in mercury-dependent mechanisms of the CMI development and progression. Int J Occup Med Environ Health 2017;30(1):77-85121030* field[33]:,61250,0,2.html Not in File B?JRChou, W.-C. Lee, P.-H. Tan, Y.-Y. Lin, H.-C. Yang, C.-W. Chen, K.-H. Chuang, C.-Y.2017An integrative transcriptomic analysis reveals bisphenol A exposure-induced dysregulation of microRNA expression in human endometrial cellsToxicology in Vitro,online early: doi: 10.1016/j.tiv.2017.02.012not published, 01 Mar 17Qanalysis Bisphenol A BISPHENOL-A CANCER carcinogenesis carcinogenic CELL CELL PROLIFERATION Development DNA DNA repair DNA repair gene EXPOSURE family GENE EXPRESSION HUMAN IS LEVELS MECHANISM Microarray microRNA microRNAs Pathway PATIENT PLASTICS POLYCARBONATE PROTEIN Regulation RISK Risk factor RISK FACTORS STUDY TREATMENT tumor ZINC 2/23/2017Bisphenol A (BPA) are commonly used in the manufacture of polycarbonate plastics. Higher BPA exposure levels have been found in patients with endometrial hyperplasia that is one of risk factors of endometrial cancer (EC). Aberrant microRNAs (miRNAs) regulation has been observed in the development of cancer. Thus, this study investigated whether BPA exposure can disrupt miRNA regulation and its gene expression regarding to EC carcinogenic progress. Microarray experiments of miRNA and mRNA were performed in human endometrial cancer RL95-2 cells with treatment of low-to-moderate (10, 103 and 105nM) BPA to explore the aberrant genes corresponding to human EC progression. According to the analysis of KEGG pathway and Cytoscape gene network, this study identified that BPA exposure reduced miR-149 expression to down-regulate DNA repair gene ARF6 (ADP-ribosylation factor 6) and tumor protein p53 (TP53), and up-regulate CCNE2 (cyclin E2) potentially to interrupt cell cycle. BPA also increased miR-107 to suppress hedgehog signaling factors, suppressor of fused homolog (SUFU) and GLI family zinc finger 3 (GLI3) to activate hedgehog signaling for cell proliferation underlying carcinogenesis. Furthermore, the BPA-induced cell proliferation was attenuated by transfection with miR-149 mimic and miR-107 inhibitor. These findings provided an insight into potential epigenetic mechanism of BPA exposure on the risk of endometrial carcinogenesis121124+ field[33]: Not in File KB?K3Claudet, I. Le Breton, M. Brehin, C. Franchitto, N.2017jA 10-year review of cannabis exposure in children under 3-years of age: do we need a more global approach?European Journal of Pediatrics,online early: doi: 10.1007/s00431-017-2872-5not published, 01 Mar 17ABUSE ACCIDENTAL ADDICTION ADULT Age CANNABIS case child CHILDREN Cohort Cohort studies Cohort study Consumption DEATH Deaths Emergencies emergency EMERGENCY DEPARTMENT Environment EXPOSURE family GCS hashish HOME IMPAIRMENT ingested INTENSIVE CARE intensive care unit INTOXICATION IS NEUROLOGICAL NO Observation outcome PAEDIATRIC pediatric POISONING poisonings Potency RESIN REVIEW seizure SEIZURES SEVERITY STUDY TEST THC unintentional UNIT URINE use VENTILATION WEIGHT Young Adult Young adults 2/16/2017 Pediatricians working in an emergency environment are confronted with children admitted to emergency departments for intoxication on a daily basis. We carried out a retrospective cohort study of children admitted to a pediatric emergency department due to unintentional cannabis exposure over a 10-year period from 2004 to 2014. Twenty-nine children under the age of 3 were admitted with a positive cannabis urine test. Eighty-seven percent of intoxications occurred at the family home. Resin was the main form of ingested cannabis (69%). The mean age was 16.5 +/- 5.2 months, and mean weight was 11.1 +/- 2.1 Kg. Sixty percent of admissions occurred between 2012 and 2014. More severe presentations, based on Poisoning Severity Score, occurred over the past 2 years. Four children experienced seizures before admission. Ten children (34%) had a decreased level of consciousness (GCS <12) and were admitted to a pediatric intensive care unit for 12-24 h. All of them had ingested hashish (resin). The majority (70%) of children suffering from neurological impairment were admitted in the last year, of whom three required assisted ventilation. There were no cases with major outcomes and no deaths. Parents were not assessed regarding their cannabis consumption. CONCLUSION: This study supports the impression that accidental child poisonings with cannabis have been more serious than previously thought for 2 years. This observation may be explained by (1) the increased THC concentration in cannabis and (2) the widespread use in young adults, even after they become parents. Introducing an addiction team inside the PED could help to improve the care links with these parents. What is Known: * Cases of unintentional cannabis intoxication in children have been increasing for many years due to an increase of potency. What is New: * We highlight an increase in more severe presentations in children under the age of 3 occurring over the past 2 years, which will indicate the importance of assessing cannabis abuse in parents by a specialized addiction team121001+ field[33]: Not in File (B?L5Corwin, D.J. Topjian, A. Banwell, B.L. Osterhoudt, K.2017qAdverse events associated with a large dose of intravenous lipid emulsion for suspected local anesthetic toxicityClinical Toxicology0online early: doi: 10.1080/15563650.2017.1294693not published, 03 Mar 17ACIDOSIS Adverse adverse event Adverse events anaesthetic ANAESTHETICS Anesthetic ANTIDOTE Antidotes As BICARBONATE BLOOD BRAIN CARDIOVASCULAR case complications DATA DOSAGE dose DRUG EYE FOOD HOSPITAL Imaging INFUSION INJECTION interpretation INTRAVENOUS IS Laboratories LABORATORY LACTATE LIPID Lipid emulsion LIPID EMULSION THERAPY MAGNETIC RESONANCE magnetic resonance imaging METABOLIC ACIDOSIS MONITORING MUSCLE NERVE OVERDOSE PATIENT seizure SEIZURES SERUM signal TACHYCARDIA THERAPY Toxicities TOXICITY TREATMENT TRIGLYCERIDE 2/26/2017Background: Intravenous lipid emulsion (ILE) has gained favor as a rescue treatment for cardiovascular collapse due to intravenous local anesthetic overdose, however, goals of ILE therapy are still being defined. We describe a case of a girl given 66 mL/kg of 20% lipid emulsion (ILE) in the treatment of presumed mepivacaine toxicity.Case report: An 11-year-old girl weighing 55.6 kg developed pallor, rolling back of the eyes, and rhythmic muscle twitching after receiving a mandibular nerve block injection with a 1.8 mL ampule of 3% mepivacaine. With concern for persistent seizures she was given three 1 mL/kg boluses of ILE, followed by an infusion of 0.25 mL/kg/min. The total dose ultimately administered was 3670 mL (66 mL/kg) over 7 h. A serum triglyceride concentration, drawn 2 h after cessation of ILE infusion, was estimated to be 16,583 mg/dL (429 mmol/L) after several dilutions; her blood was grossly lipemic. Notable signs included hypersomnolence, tachypnea, and tachycardia. Other complications included apparent metabolic acidosis (serum bicarbonate of 5 mmol/L) with hyperlactatemia (lactate 7.0 mmol/L), difficulty with serum laboratory interpretation, and a non-contrast brain magnetic resonance imaging showing high signal in the dural venous sinuses. The lipemia cleared over three days and the patient recovered uneventfully.Case discussion: This case demonstrates a unique neurologic and metabolic toxicity associated with ILE given as an antidote in a high total dose, and highlights the need for cautious antidotal application of lipid emulsion infusions. Until more data is available, clinicians are advised to take great care if considering a dose in excess of 12.5 mL/kg/day, the maximum daily dosage recommended by the U.S. Food and Drug Administration for nutritional supplementation. Careful monitoring of total doses administered across institutions and hospital wards during transfers is paramount to avoid inadvertent overdose of antidotes121156/ field[33]: Not in FileB?M-Coulson, J.M. Caparrotta, T.M. Thompson, J.P.2017>The management of ventricular dysrhythmia in aconite poisoningClinical Toxicology0online early: doi: 10.1080/15563650.2017.1291944not published, 03 Mar 17ACONITE ACUTE acute poisoning agent ALKALOIDS AMIODARONE ANIMAL ARRHYTHMIA Arrhythmias As author BYPASS CARDIOPULMONARY CARDIOPULMONARY BYPASS Cardiopulmonary Resuscitation CARDIOTOXICITY CARDIOVASCULAR Cardiovascular toxicity case CASE REPORT case reports Case-report CLINICAL DATA DRUG Drug treatment dysrhythmia DYSRHYTHMIAS EPINEPHRINE evidence EXPOSURE FLECAINIDE GOOGLE HEART HUMAN Humans INFORMATION ingested ION CHANNEL IS LIDOCAINE MAGNESIUM MAGNESIUM SULPHATE MANAGEMENT MEXILETINE MORTALITY MYOCARDIUM outcome PAPER PATIENT PLANT POISONING PROCAINAMIDE RESUSCITATION REVIEW SODIUM SODIUM CHANNEL STUDY SULPHATE TACHYCARDIA toxic toxic effects Toxicities TOXICITY TREATMENT use ventricular ectopy VENTRICULAR FIBRILLATION VENTRICULAR TACHYCARDIA 2/20/2017Introduction: Aconite poisoning is relatively rare but is frequently complicated by ventricular dysrhythmias, which may be fatal.Molecular basis of aconite alkaloid ventricular arrhythmogenicity: Aconite exerts its toxic effects due to the presence of an admixture of alkaloids present in all parts of the plant. The major target of these aconite alkaloids is the fast voltage-gates sodium channel, where they cause persistent activation. This blockade of the channel in the activated state promotes automaticity within the ventricular myocardium and the generation of ventricular arrhythmias.Aconitine-induced arrhythmias: Aconite alkaloids are known to cause many different types of disturbance of heart rhythm. However, this focused review specifically looks at ventricular rhythm disturbances, namely ventricular ectopy, ventricular tachycardia, torsades des pointes and ventricular fibrillation.Objective: The objective of this review was to identify the outcome of anti-dysrhythmic strategies from animal studies and case reports in humans in order to guide the management of ventricular dysrhythmias in aconite poisoning in humans.Methods: A review of the literature in English was conducted in PubMed and Google Scholar from 1966 to July 2016 using the search terms "aconite/aconitine"; "aconite/aconitine"+"poisoning" and "aconite/aconitine"+"dysrhythmia". 168 human case-reports and case-series were identified by these searches, of which 103 were rejected if exposure to aconite did not result in ventricular dysrhythmias, if it was uncertain as to whether aconite had been ingested, if other agents were co-ingested, if there was insufficient information to determine the type of treatments administered or if there was insufficient information to determine outcome. Thus, 65 case reports of probable aconite poisoning that resulted in ventricular dysrhythmias were identified.Toxicokinetic data in aconite poisoning: Data were only available in three papers; the presence of ventricular rhythm disturbances directly correlated with the concentration of aconite alkaloids in the plasma.Management: 54 of 65 cases developed ventricular tachycardia, six developed torsades des pointes, 15 patients developed ventricular fibrillation, 10 developed ventricular ectopics and one developed a broad complex tachycardia not otherwise specified; each dysrhythmia was regarded as separate and patients may have had more than one dysrhythmia. 10 patients died, giving a mortality of 15%. In total, 147 treatments were administered to 65 patients. 46 of the interventions were assessed by the authors as having been associated with successful restoration of sinus rhythm. Flecainide administration was accompanied by dysrhythmia termination in six of seven cases. Mexiletine was connected with correcting dysrhythmias in 3 of 3 cases. Procainamide administration was associated with return to sinus rhythm in 2 of 2 cases. Prolonged cardio-pulmonary resuscitation was administered to 15 patients where it was associated with a return to sinus rhythm in nine of these. Amiodarone was linked to success in correcting dysrhythmias in 11 of 20 cases. Cardiopulmonary bypass use was associated with a return to sinus rhythm in four out of six cases. Epinephrine was documented as being employed on four occasions, and was associated with a restoration of sinus rhythm on two of these. Magnesium sulphate administration was accompanied by dysrhythmia termination in two of nine cases. Direct cardioversion was associated with a return of sinus rhythm in 5 of 30 cases. However, it is not certain whether the drug treatment influenced the course of the dysrhythmia.Conclusions: Based on the evidence available from human case reports, flecainaide or amiodarone appear to be more associated with a return to sinus rhythm than lidocaine and/or cardioversion, although it is not established whether the administration of treatment caused reversion to normal sinus rhythm. The potential beneficial effects of amiodarone were not observed in animal studies. This may be due to intra-species differences between ion channels or relate to the wider cardiovascular toxicity of aconite that extends beyond arrhythmias. Prolonged cardiopulmonary resuscitation and cardiopulmonary bypass should be considered as an integral part of good clinical care as ?time-buying? strategies to allow the body to excrete the toxic alkaloids. There may also be a role for mexiletine, procainamide and magnesium sulphate121154/ field[33]: Not in File ?NZCousins, G. Boland, F. Barry, J. Lyons, S. Keenan, E. O'Driscoll, D. Bennett, K. Fahey, T.2017J-shaped relationship between supervised methadone consumption and retention in methadone maintenance treatment (MMT) in primary care: national cohort study126-131Drug and Alcohol Dependence173/Age As Association Cohort Cohort studies Cohort study Consumption discontinuation dose FOLLOW UP Follow-up Gender HAZARD IS maintenance maintenance treatment METHADONE Methadone maintenance Methadone maintenance therapy method methods MODEL NO PATIENT STUDY supervised consumption THERAPY Time TREATMENT 1/25/2017NBACKGROUND: Supervised consumption ensures patients take methadone as prescribed and prevents diversion, however, the influence of supervised consumption on retention is unclear. We examined association between supervised consumption and retention across multiple treatment episodes. METHODS: Cohort study of persons experiencing >/=1 MMT episodes in primary care (2004-2010), excluding ongoing episodes at the start of follow-up. Length of treatment episodes based on methadone prescriptions, retention classified as no interruption in prescribed methadone lasting >7 days. When a patient did not receive a new prescription within seven days after the end of coverage of a prescription, they were considered to have ceased treatment. We evaluated the relationship between supervised consumption and time to discontinuation of treatment using proportional hazards gamma frailty models to account for recurrent MMT episodes. Age, gender, median daily methadone dose, and comorbidities included as potential confounders. RESULTS: 6393 patients experienced 19,715 treatment episodes over the six-year follow-up period. A J-shaped relationship was observed; having between 20 and 60% of methadone scripts supervised (compared to <20%) associated with reduced time to discontinuation (20-39% HR=0.88, 95% CI 0.81-0.95; 40-59%: HR=0.87, 95% CI 0.81-0.94). Beyond a threshold of 60%, retention reduced (60-79% of scripts: HR=1.28, 95% CI 1.20-1.36;>80% of scripts: HR=3.59, 95% CI 3.38-3.81). Median daily dose between 60 and 120mg/per day, and multiple treatment episodes also associated with longer time to discontinuation of treatment. CONCLUSION: A J-shaped relationship was observed between supervised consumption and retention in treatment. Additionally, patients experiencing multiple treatment episodes tend to stay in treatment for progressively longer periods of time1209782 field[33]: Not in FileB?OnCuypers, E. Rosier, E. Loix, S. Develter, W. Van Den Bogaert, W. Wuestenbergs, J. Van de Voorde, W. Tytgat, J.2017bMedical findings and toxicological analysis in infant death by balloon gas asphyxia: a case report Journal of Analytical Toxicology%online early: doi: 10.1093/jat/bkx006not published, 28 Feb 17Ganalysis ANALYTICAL As ASPHYXIATION AUTOPSY case CASE REPORT Case-report CHILDREN DEATH DOXYLAMINE FORENSIC GA GAS gas chromatography mass spectrometry Gas chromatography-mass spectrometry HELIUM HOMICIDE INFANT INHALATION IS LEVELS LUNG lung tissue NITROGEN NO PAEDIATRIC Qualitative Sedation SPECTROMETRY SUICIDE TISSUE toxic2/7/2017MIn recent years, the increasing number of asphyxiation cases due to helium inhalation is remarkable. All described cases in the literature where diagnosed as suicide. In this article, however, we describe a triple infant homicide in which helium, as balloon gas, was administered to three young children after sedation causing asphyxiation and death through the medical findings and toxicological analysis. During autopsy, in addition to standard toxicological samples, gas samples from lungs as well as lung tissue itself were directly collected into headspace vials. Besides routine toxicological analysis, which revealed toxic levels of doxylamine, qualitative analysis on gas and lung samples was performed using headspace gas chromatography-mass spectrometry. As carrier gas, the commonly used helium was replaced by nitrogen. In gas samples from lungs of all three children, no helium was found. Nevertheless, lung tissue samples were found positive on helium. Therefore, sedation followed by asphyxia due to helium inhalation can strongly be assumed as the cause of death of all three children.120895$ field[33]: Not in FileB?P0Cvetkovic, D. Zivkovic, V. Lukic, V. Nikolic, S.2017[Unnatural and violent death in cases with high blood alcohol concentration— Autopsy studyJ Forensic Sci*online early: doi: 10.1111/1556-4029.13460not published, 01 Mar 17ACCIDENTAL Accidents Age ALCOHOL As AUTOPSY BLOOD Blood alcohol concentration case CONCENTRATIONS DEATH Deaths DISTRIBUTION EXPOSURE FATAL FIRE FOOD FORENSIC Gender INTOXICATION IS NO RISK STUDY SUICIDE use WHO 2/23/2017The use of alcohol increases the risk of dying from unnatural or violent causes. The presented study explored the distribution of age, gender, cause, and circumstances of death in persons who died in an unnatural and violent manner, with a blood alcohol concentration (BAC) higher than 0.3 g/dL, and where the cause of death was not alcohol intoxication. We defined the control (0 < BAC < 0.3 g/dL) and study (BAC >/= 0.3 g/dL) groups, as in subjects with these concentrations, there is a significant risk of gross intoxication, stupor, and death. The subjects from the study group were older, with no difference in gender distribution. Traffic accidents were the most common fatal event in both groups, followed by suicides. Other accidents (choking on food and exposure to fire) were more frequent in the study group. Compared to the control group, subjects from the study group were older persons whose deaths were mainly accidental121049) field[33]: Not in File?Q3Dadhania, V.P. Bhushan, B. Apte, U. Mehendale, H.M.2017{Wnt/beta-catenin signaling drives thioacetamide-mediated heteroprotection against acetaminophen-induced lethal liver injury1559325817690287 Dose Response151ACETAMINOPHEN ANIMAL Animals CYP2E1 DATA dose EXPOSURE HEPATIC HEPATOTOXICITY injuries Injury IS lethal lethality LIVER liver injury MALE MECHANISM Mechanisms MICE MODEL OVERDOSE PARACETAMOL Pathway PRETREATMENT THIOACETAMIDE Time Time Course TISSUE Toxicant Vehicle WATER1/2017rPreplacement of compensatory tissue repair (CTR) by exposure to a nonlethal dose of a toxicant protects animals against a lethal dose of another toxicant. Although CTR is known to heteroprotect, the underlying molecular mechanisms are not completely known. Here, we investigated the mechanisms of heteroprotection using thioacetamide (TA): acetaminophen (APAP) heteroprotection model. Male Swiss Webster mice received a low dose of TA or distilled water (DW) vehicle 24 hours prior to a lethal dose of APAP. Liver injury, tissue repair, and promitogenic signaling were studied over a time course of 24 hours after APAP overdose to the TA- and DW-primed mice (TA + APAP and DW + APAP, respectively). Thioacetamide pretreatment afforded 100% protection against APAP overdose compared to 100% lethality in the DW + APAP-treated mice. Although hepatic Cyp2e1 was similar at the time of APAP administration, immediate activation of hepatic c-Jun N-terminal kinases (JNK) was observed in the TA + APAP-treated mice compared to its delayed activation in the DW + APAP group. In contrast to the DW + APAP group, the TA + APAP-treated mice exhibited extensive CTR, which was secondary to the timely activation of Wnt/beta-catenin pathway. Our data indicate that rapid activation and appropriate termination of Wnt/beta-catenin signaling and modulation of JNK activity underlie TA + APAP heteroprotection120977- field[33]: Not in File DB?R Darius, H.2017=NOAK: Real-life-Daten und Therapie von Blutungen mit Antidots8Medizinische Klinik - Intensivmedizin und Notfallmedizin,online early: doi: 10.1007/s00063-016-0258-5not published, 16 Feb 17Aanalysis ANTAGONIST ANTIBODIES ANTICOAGULANT anticoagulants ANTIDOTE Antidotes As CLINICAL COAGULATION Cohort complications dabigatran DATA DRUG Emergencies emergency evidence HEALTH Idarucizumab IS MANAGEMENT Modified MONOCLONAL ANTIBODIES PATIENT PREVENTION PUBLIC PUBLIC HEALTH RISK THERAPY TRIAL use vitamin VITAMIN K 1/31/2017\The non-vitamin K antagonists (NOAC) are an integral component of our antithrombotic prevention and therapy. For four of the NOAC, their non-inferiority or even superiority versus vitamin K antagonists (VKA) has been proven. Thus, the management of special patient cohorts or the management of active bleeding complications is a focus of current discussion.In addition to prospective trials, numerous retrospective analyses of health insurers or public health provider data have been analyzed and published as "real life" or "real-world evidence" data. In almost all data sets the results of the NOAC approval trials were confirmed, demonstrating their non-inferiority or even superiority versus VKA. Attempts to compare the various NOAC with each other must be viewed critically since the real-world evidence (RWE) analysis provides very divergent results depending on the cohorts analyzed. Thus, a substantial prescriber-bias must be taken into account and never be excluded.In order to improve the management of bleeding complications, NOAC antidotes were developed. While the factors Xa antidote, andexanet alpha, a modified coagulation factor deleted of an intrinsic activity, will not be available before 2018, the dabigatran antidote idarucizumab is already in clinical use. Idarucizumab, a monoclonal antibody fragment directed against dabigatran, is able to completely antagonize the effect of dabigatran within minutes. Therefore, the drug has the potential to terminate life-threatening bleeding complications earlier and make emergency surgical or interventional procedures possible without an elevated bleeding risk120714+ field[22]: [NOAC: Real-life data and the role of antidotes for the treatment of bleeding]. In German with English abstract RefMgr field[33]: Not in File2B?SMDas, A. Mallick, I. Arun, P. Midha, D. Sen, S. Krishnan, S. Bhattacharyya, A.2017Encouraging outcomes with manageable toxicity using neoadjuvant chemotherapy and intensity-modulated radiotherapy in advanced pediatric nasopharyngeal carcinoma: single-center experience from a developing country(Journal of Pediatric Hematology/Oncology/online early: doi: 10.1097/MPH.0000000000000794not published, 01 Mar 17TCARCINOMA CHEMOTHERAPY outcome PAEDIATRIC pediatric RADIOTHERAPY Toxicities TOXICITY 2/23/2017121053/ field[33]: Not in Fileb?T9de Flines, E.W. Bolwerk, C.J. Komen, B.J. Veenhoven, W.A.19906Abnormal metabolism of phenylbutazone after overdosage783Annals of Pharmacotherapy247-8ACETATE ALANINE ALKALINE ALKALINE PHOSPHATASE As Bilirubin case CASE REPORT case reports Case-report CHROMATOGRAPHY COMPARATIVE CONCENTRATIONS CREATININE DETECTION dose DRUG ELECTROCARDIOGRAM ELIMINATION ETHANOL evidence EXCRETION EXTRACTION hemoglobin HEPATIC HOSPITAL INJECTION IS Laboratories LABORATORY LETTER Liquid chromatography LIVER LIVER FUNCTION MECHANISM Mechanisms MEDROXYPROGESTERONE METABOLISM METABOLITE Metabolites METHANOL Modified NO NSAID NSAIDs overdosage PATIENT pH PHENYLBUTAZONE physical examination PLASMA PROTEIN proteins RENAL RESIDUE RESPIRATORY RESPIRATORY SYMPTOMS SERUM SINGLE-DOSE SODIUM SYMPTOMS TEST ULTRAVIOLET use1990120819, field[33]: Not in File r?U*Dellafiora, L. Galaverna, G. Dall'asta, C.2017In silico analysis sheds light on the structural basis underlying the ribotoxicity of trichothecenes—A tool for supporting the hazard identification process80-87Toxicology Letters270]Affect analysis ANIMAL Animals As ASSESSMENT BETA DEOXYNIVALENOL family FUNGI Glycosylation HAZARD HEALTH Health risk HUMAN IDENTIFICATION in silico Inhibition injuries Injury INTERACTION IS MECHANISM MODEL Modified Mycotoxin MYCOTOXINS PLANT plants POSITION PROTEIN RISK RISK ASSESSMENT STRUCTURE-ACTIVITY STUDY Synthesis toxic toxin TRICHOTHECENES 2/16/2017Deoxynivalenol is a foodborne mycotoxin belonging to the trichothecenes family that may cause severe injuries in human and animals. The inhibition of protein synthesis via the interaction with the ribosome has been identified as a crucial mechanism underlying toxic action. However, it is not still fully understood how and to what extent compounds belonging to trichothecenes family affect human and animal health. In turn, this scenario causes delay in managing the related health risk. Aimed at supporting the hazard identification process, the in silico analysis may be a straightforward tool to investigate the structure-activity relationship of trichothecenes, finding out molecules of possible concern to carry forth in the risk assessment process. In this framework, this work investigated through a molecular modeling approach the structural basis underlying the interaction with the ribosome under a structure-activity relationship perspective. To identify further forms possibly involved in the total trichothecenes-dependent ribotoxic load, the model was challenged with a set of 16 trichothecene modified forms found in plants, fungi and animals, including also compounds never tested before for the capability to bind and inhibit the ribosome. Among them, only the regiospecific glycosylation in the position 3 of the sesquiterpenoid scaffold (i.e. T-2 toxin-3-glucuronide, alpha and beta isomers of T-2 toxin-3-glucoside and deoxynivalenol-3-glucuronide) was found impairing the interaction with the ribosome, while the other compounds tested (i.e. neosolaniol, nivalenol, fusarenon-X, diacetoxyscirpenol, NT-1 toxin, HT-2 toxin, 19- and 20-hydroxy-T-2 toxin, T-2 toxin triol and tetraol, and 15-deacetyl-T-2 toxin), were found potentially able to inhibit the ribosome. Accordingly, they should be included with high priority in further risk assessment studies in order to better characterize the trichothecenes-related hazard121126. field[33]: Not in File B?V!Devries, J. Rafie, S. Polston, G.2017WImplementing an overdose education and naloxone distribution program in a health system/Journal of the American Pharmacists Association-online early: doi: 10.1016/j.japh.2017.01.002not published, 01 Mar 17As baseline California DEATH Deaths Development DISTRIBUTION EDUCATION EVALUATION fatalities fatality Guidelines HEALTH HOSPITAL IS NALOXONE OPIOID Opioid overdose OVERDOSE PATIENT PRESCRIBING RESPONSE RATE RISK SAFETY SERVICE 2/20/2017OBJECTIVE: To design and implement a health system-wide program increasing provision of take-home naloxone in patients at risk for opioid overdose, with the downstream aim of reducing fatalities. The program includes health care professional education and guidelines, development, and dissemination of patient education materials, electronic health record changes to promote naloxone prescriptions, and availability of naloxone in pharmacies. SETTING: Academic health system, San Diego, California. PRACTICE DESCRIPTION: University of California, San Diego Health (UCSDH), offers both inpatient and outpatient primary care and specialty services with 563 beds spanning 2 hospitals and 6 pharmacies. UCSDH is part of the University of California health system, and it serves as the county's safety net hospital. PRACTICE INNOVATION: In January 2016, a multisite academic health system initiated a system-wide overdose education and naloxone distribution program to prevent opioid overdose and opioid overdose-related deaths. An interdisciplinary, interdepartmental team came together to develop and implement the program. To strengthen institutional support, naloxone prescribing guidelines were developed and approved for the health system. Education on naloxone for physicians, pharmacists, and nurses was provided through departmental trainings, bulletins, and e-mail notifications. Alerts in the electronic health record and preset naloxone orders facilitated co-prescribing of naloxone with opioid prescriptions. EVALUATION: Electronic health record reports captured naloxone prescriptions ordered. Summary reports on the electronic health record measured naloxone reminder alerts and response rates. RESULTS: Since the start of the program, the health system has trained 252 physicians, pharmacists, and nurses in overdose education and take-home naloxone. There has been an increase in the number of prescriptions for naloxone from a baseline of 4.5 per month to an average of 46 per month during the 3 months following full implementation of the program including implementation of electronic health record alerts. CONCLUSION: Initiating and implementing an overdose education and naloxone distribution program is feasible in an academic health system121035, field[33]: Not in File 8?W,Dhawan, I. Tewari, A. Sehgal, S. Sinha, A.C.2017=Medication errors in anesthesia: unacceptable or unavoidable?184-192#Brazilian Journal of Anesthesiology672Adverse ADVERSE EFFECTS anaesthetic ANAESTHETICS As Attention burden DEATH Development dose DRUG errors harm HUMAN ICU impact IS MISUSE MORBIDITY MORTALITY NO Occurrence OVERDOSE PATIENT Preconception PROTOCOL Protocols Route safe workplace3/2017[Medication errors are the common causes of patient morbidity and mortality. It adds financial burden to the institution as well. Though the impact varies from no harm to serious adverse effects including death, it needs attention on priority basis since medication errors' are preventable. In today's world where people are aware and medical claims are on the hike, it is of utmost priority that we curb this issue. Individual effort to decrease medication error alone might not be successful until a change in the existing protocols and system is incorporated. Often drug errors that occur cannot be reversed. The best way to 'treat' drug errors is to prevent them. Wrong medication (due to syringe swap), overdose (due to misunderstanding or preconception of the dose, pump misuse and dilution error), incorrect administration route, under dosing and omission are common causes of medication error that occur perioperatively. Drug omission and calculation mistakes occur commonly in ICU. Medication errors can occur perioperatively either during preparation, administration or record keeping. Numerous human and system errors can be blamed for occurrence of medication errors. The need of the hour is to stop the blame - game, accept mistakes and develop a safe and 'just' culture in order to prevent medication errors. The newly devised systems like VEINROM, a fluid delivery system is a novel approach in preventing drug errors due to most commonly used medications in anesthesia. Similar developments along with vigilant doctors, safe workplace culture and organizational support all together can help prevent these errors120956- field[33]: Not in File ?XDhooria, S. Agarwal, R.20167Amitraz, an underrecognized poison: a systematic review348-358"Indian Journal of Medical Research1443ABSTRACT ACCIDENTAL ACTIVATED CHARCOAL ADULT agent AMITRAZ As BRADYCARDIA case CASE REPORT case reports Case-report Charcoal CHILDREN CLINICAL DATABASE DEATH Deaths DECONTAMINATION DIAGNOSIS EPIDEMIOLOGY FAILURE family fatalities fatality FEMALE GASTRIC GASTRIC LAVAGE HUMAN HUMAN POISONING HYPERGLYCAEMIA HYPOTENSION HYPOTHERMIA INFORMATION interpretation INTOXICATION IS LAVAGE MANAGEMENT Mechanical ventilation MECHANISM Mechanisms MEDLINE method methods MIOSIS organophosphate OVERDOSE PATIENT pesticide PESTICIDES Poison POISONING PROGNOSIS RESPIRATORY RESPIRATORY FAILURE REVIEW STUDY suicidal systematic review Toxicities TOXICITY TOXICOKINETIC toxicokinetics VENTILATION Vomiting9/2016BACKGROUND & OBJECTIVES: Amitraz is a member of formamidine family of pesticides. Poisoning from amitraz is underrecognized even in areas where it is widely available. It is frequently misdiagnosed as organophosphate poisoning. This systematic review provides information on the epidemiology, toxicokinetics, mechanisms of toxicity, clinical features, diagnosis and management of amitraz poisoning. METHODS: Medline and Embase databases were searched systematically (since inception to January 2014) for case reports, case series and original articles using the following search terms: 'amitraz', 'poisoning', 'toxicity', 'intoxication' and 'overdose'. Articles published in a language other than English, abstracts and those not providing sufficient clinical information were excluded. RESULTS: The original search yielded 239 articles, of which 52 articles described human cases. After following the inclusion and exclusion criteria, 32 studies describing 310 cases (151 females, 175 children) of human poisoning with amitraz were included in this systematic review. The most commonly reported clinical features of amitraz poisoning were altered sensorium, miosis, hyperglycaemia, bradycardia, vomiting, respiratory failure, hypotension and hypothermia. Amitraz poisoning carried a good prognosis with only six reported deaths (case fatality rate, 1.9%). Nearly 20 and 11.9 per cent of the patients required mechanical ventilation and inotropic support, respectively. The role of decontamination methods, namely, gastric lavage and activated charcoal was unclear. INTERPRETATION & CONCLUSIONS: Our review shows that amitraz is an important agent for accidental or suicidal poisoning in both adults and children. It has a good prognosis with supportive management120715* field[33]: year=2016 volume=144 issue=3 spage=348 epage=358 aulast=Dhooria Not in File?Y2Di Mare, V. Garramone, G. Rubbiani, M. Moretto, A.2017[Quality check of safety data sheets for plant protection product co-formulants: hazard classification and coherence of the information]33-41Medicina del Lavoro1081As chemical CHEMICALS DATA EVALUATION HAZARD INFORMATION method methods PLANT quality Regulation SAFETY Safety data sheet SDS SEVERITY STUDY 2/15/2017BACKGROUND: Hazard classification of chemicals can be defined as a logic-mathematical operation aimed at identifying the type and severity of the inherent hazards of a substance or a mixture. OBJECTIVES: The purpose of this study was to evaluate, in 134 safety data sheets (SDSs): i) the hazard classification and ii) its coherence with sections 9 (physical-chemical properties), 11 (toxicological properties) and 12 (ecological properties) of the SDSs. METHODS: Hazard classification and the information provided in sections 9, 11 and 12 of the SDSs have been evaluated against the criteria provided in annexes VI of the Dangerous Substance Directive, II and III of the Dangerous Preparations Directive, I and VI of the Regulation (EC) n. 1272/2008. RESULTS: Most of the analyzed SDSs of substances (62%) was associated to non-classified chemicals (61.4%), although 19.6% of them should have been classified. By contrast, 59.4% of classified substances (representing 38.6% of analyzed ones) were wrongly classified. Fifty-four %, 54% and 67% of suggested substances hazard classification were in line with sections 9 (physical-chemical properties), 11 (toxicological properties) and 12 (ecological properties). CONCLUSIONS: The proportion of hazard classification mistakes in SDS was significant, suggesting the need of more qualified experts to derive classification. The introduction of an ad hoc evaluation team, managed by a single, qualified specialist, could represent a solution to ensure the needed improvement of SDSs quality121178+ field[22]: In Italian with English abstract Not in File?ZDíaz-Antón, B. Alonso-Deniz, G. Perez-Vela, J.L. Molina-Martin de Nicolás, J. Rubio-Alonso, B. Jurado-Román, A. Miguel-Gutierrez, A. Martin-Asenjo, R.2017F'Jamaican Stone': a potentially lethal remedy for delaying ejaculation 143.e1-143.e4!Revista Portuguesa de Cardiologia362>case DIAGNOSIS INGESTION IS lethal MORTALITY POISONING STEROID2/1/20178Poisoning by ingestion of 'Jamaican Stone', a kind of cardioactive steroid, is extremely rare. However, mortality is very high. For this reason, when it occurs, an early and accurate diagnosis represents a critical challenge for clinicians. We present an unusual case of electrical storm caused by this substance120716, field[33]: Not in File B?[)Doleschal, B. Petzer, A. Aichberger, K.J.2017Taxan-associated nail toxicityBMJ Case Reportsdoi:10.1136/bcr-2016-218980YAged BREAST CANCER CANCER CHEMOTHERAPY CLINICAL docetaxel NEUTROPENIA Toxicities TOXICITY 1/31/2017120703) field[33]: Not in FileB?\MDominguez-Lopez, P. Diaz-Cueto, L. Aguilar-Rojas, A. Arechavaleta-Velasco, F.2017Synergistic effect of DDT and its metabolites in lipopolysaccharide-mediated TNF-alpha production is inhibited by progesterone in peripheral blood mononuclear cells/Journal of Biochemical and Molecular Toxicology$online early: doi: 10.1002/jbt.21907not published, 01 Mar 17Adverse BLOOD CELL DDE DDT ELISA IS LEVELS Lipopolysaccharide MALARIA METABOLITE Metabolites oc ORGANOCHLORINE outcome PERIPHERAL pesticide PESTICIDES PREGNANCY Pregnancy outcome PROGESTERONE Release STUDY Synthesis WOMEN 2/26/2017Increased TNF-alpha levels have been associated with adverse pregnancy outcomes. Lipopolysaccharide (LPS), 1,1,1-trichloro-2,2-bis-(chlorophenyl)ethane (DDT), 1,1-bis-(chlorophenyl)-2,2-dichloroethene (DDE), and 1,1-dichloro-2,2-bis(chlorophenyl)ethane (DDD) induce TNF-alpha release in peripheral blood mononuclear cells (PBMC). Conversely, progesterone (P4) inhibits TNF-alpha secretion. Pregnant women in malaria endemic areas may be co-exposure to these compounds. Thus, this study was to investigate the synergistic effect of LPS and these pesticides in PBMC and to assess P4 influence on this synergy. Cultured PBMC were exposed to each pesticide in the presence of LPS, P4, or their combination. TNF-alpha was measured by ELISA. All pesticides enhanced TNF-alpha synthesis in PBMC. Co-exposure with LPS synergizes TNF-alpha production, which is blocked by progesterone. These results indicate that these organochlorines act synergistically with LPS to induce TNF-alpha secretion in PBMC. This effect is blocked by P4121041# field[33]: Not in File QB?]BDownes, M.A. Balshaw, J.K. Muscat, T.M. Ritchie, N. Isbister, G.K.2017_Impact of an emergency short stay unit on emergency department performance of poisoned patients&American Journal of Emergency Medicine-online early: doi: 10.1016/j.ajem.2017.01.027#not published, 16 Feb 17, 17 Mar 17ACUTE acute poisoning ADULT CLINICAL DATA DATABASE DISPOSITION Emergencies emergency EMERGENCY DEPARTMENT EXPOSURE HOSPITAL impact MET method methods NO outcome PATIENT POISONING STUDY TOXICOLOGY toxin TOXINS TREATMENT UNIT 1/26/2017OBJECTIVES: This was a before and after study which sought to assess the impact of opening an ED short stay unit (ESSU) on the ED performance of poisoned patients. METHODS: Data was collected from two groups of adult patients presenting to an ED with a tertiary referral inpatient Toxicology unit from the 2009 and 2012 calendar years, to assess the impact of the ESSU. The toxicology unit clinical database and hospital electronic medical records were interrogated for demographic, clinical and hospital flow details of presentations. The primary outcome was ED length of stay (LOS). Other outcomes included proportion of patients remaining in ED for their admission, 28day re-presentations and hospital LOS. RESULTS: During 2009, 795 patients met inclusion criteria, and during 2012, 762. The median LOS in ED was reduced from 8.5 h (IQR: 4.7-14 h) to 2.7 h (IQR: 1.6-4.6; p<0.0001). The proportion of patients remaining in ED for their entire hospital stay was reduced from 515/795 (65%) to 56/762 (7.3%) [Absolute difference: 57%; 95% CI: 53 to 62%; p<0.0001]. Total hospital LOS increased from 14.5 h (IQR: 8.4-21.8 h) to 16.7 h (IQR: 11.5-23; p<0.0001), but there was a decrease in re-presentations with self-poisoning within 28days from 6.9% in 2009 to 4.5% in 2012 (p<0.038). There was no difference between disposition destination or toxins causing exposure between the two groups. CONCLUSIONS: The ESSU led to a significant improvement in ED performance of poisoned patients. It also potentially assisted in reducing ED overcrowding120691, field[33]: Not in File?^J#Duberkar, D.R. Jawale, R. Aghor, N.2016JManganism in patients with chronic renal failure on long term hemodialysisMP28/77%Annals of Indian Academy of Neurology1968ABSTRACT BASAL GANGLIA BRAIN CHELATION CHRONIC DIAGNOSIS DIALYSIS DISEASE ENCEPHALOPATHY FAILURE HAEMODIALYSIS hemodialysis IS LEVELS LIVER LIVER DISEASE Long term Long-term MANAGEMENT MANGANESE MRI MYOCLONUS NEPHROTOXICITY PARKINSONISM PATIENT recovery RENAL RENAL FAILURE Renal Insufficiency STUDY SYMPTOMS WHO20161206965 Not in FileY?_ Dutta, P.2017GModeling of variability and uncertainty in human health risk assessment76-85MethodsX4ASSESSMENT DATA Environment EXPOSURE HEALTH Health risk Health risk assessment HUMAN Human health INFORMATION IS method methods MODEL PAPER Potential health risk RISK RISK ASSESSMENT Time toxic Variability2017Health risk assessments have been carried out worldwide to examine potential health risk due to exposure to toxic contaminants in various environments. In risk assessment, it is most important to know the nature of all available information, data or model parameters. It is observed that available information/data are tainted with uncertainty and variability in the same time, i.e., uncertainty and variability co-exist. In such situation it is important to devise method for processing both uncertainty and variability into same framework and which is an open issue. In this regards, this paper presents an algorithm to combined approach to propagate variability and uncertainty in the same framework. The differences and advantages of this algorithm over the existing methods are presented below: *The representation of uncertain model parameters are probabilistic together with generalized fuzzy numbers and normal interval valued fuzzy numbers.*The results obtained are then interpreted in terms of p-box and fuzzy numbers.*The advantage of this approach over the existing methods is that this approach gives an accurate resultant fuzzy number which is of trapezoidal type generalized fuzzy number that is different from the existing methods121071+ field[33]: Not in File ?`?Dutta, S.R. Passi, D. Singh, M. Singh, P. Sharma, S. Sharma, A.20165Botulinum toxin the poison that heals: a brief review10-16)National Journal of Maxillofacial Surgery71ACETYLCHOLINE agent As biological botulinum BOTULISM Clostridium botulinum DATABASE Development DISEASE GOOGLE HUMAN Humans INTENSIVE CARE IS lethality MECHANISM mechanism of action medical use MISUSE neuromuscular junction Neurotoxin neurotoxins PAPER PHARMACOLOGY Poison Potency PROTEIN proteins Release RESEARCH REVIEW scopus THERAPEUTIC toxin TRANSPORT TREATMENT use Warfare ZINC1/2016,Botulinum neurotoxins, causative agents of botulism in humans, are produced by Clostridium botulinum, an anaerobic spore-former Gram-positive bacillus. Botulinum neurotoxin poses a major bioweapon threat because of its extreme potency and lethality; its ease of production, transport, and misuse; and the need for prolonged intensive care among affected persons. This paper aims at discussing botulinum neurotoxin, its structure, mechanism of action, pharmacology, its serotypes and the reasons for wide use of type A, the various indications and contraindications of the use of botulinum neurotoxin and finally the precautions taken when botulinum neurotoxin is used as a treatment approach. We have searched relevant articles on this subject in various medical databases including Google Scholar, PubMed Central, ScienceDirect, Wiley Online Library, Scopus, and Copernicus. The search resulted in more than 2669 articles, out of which a total of 187 were reviewed. However, the review has been further constricted into only 54 articles as has been presented in this manuscript keeping in mind the page limitation and the limitation to the number of references. A single gram of crystalline toxin, evenly dispersed and inhaled, can kill more than one million people. The basis of the phenomenal potency of botulinum toxin (BT) is enzymatic; the toxin is a zinc proteinase that cleaves neuronal vesicle-associated proteins responsible for acetylcholine release into the neuromuscular junction. A fascinating aspect of BT research in recent years has been the development of the most potent toxin into a molecule of significant therapeutic utility. It is the first biological toxin which is licensed for the treatment of human diseases. The present review focuses on both warfare potential as well as medical uses of botulinum neurotoxin120909* field[33]: year=2016 volume=7 issue=1 spage=10 epage=16 aulast=Dutta Not in File?aEbrahim, I. Blockman, M.20177Metabolic acidosis in a patient with metformin overdose110-111South African Medical Journal1072GACIDOSIS ACUTE case FATAL METABOLIC ACIDOSIS METFORMIN OVERDOSE PATIENT 1/30/20171211150 field[33]: Not in File ?b^Echterbille, J. Gilles, N. Araóz, R. Mourier, G. Amar, M. Servent, D. De Pauw, E. Quinton, L.2017Discovery and characterization of EIIB, a new alpha-conotoxin from Conus ermineus venom by nAChRs affinity capture monitored by MALDI-TOF/TOF mass spectrometry1-10Toxicon130%ACETYLCHOLINE ACETYLCHOLINE RECEPTOR ANIMAL As Characterization CONOTOXIN DRUG drugs family MASS SPECTROMETRY MEMBRANE nicotinic acetylcholine receptors Nicotinic receptor nicotinic receptors PHARMACOLOGY POISONING RECEPTORS SCREENING selectivity SNAILS SPECTROMETRY TEST toxin TOXINS US Venom 2/23/2017Animal toxins are peptides that often bind with remarkable affinity and selectivity to membrane receptors such as nicotinic acetylcholine receptors (nAChRs). The latter are, for example, targeted by alpha-conotoxins, a family of peptide toxins produced by venomous cone snails. nAChRs are implicated in numerous physiological processes explaining why the design of new pharmacological tools and the discovery of potential innovative drugs targeting these receptor channels appear so important. This work describes a methodology developed to discover new ligands of nAChRs from complex mixtures of peptides. The methodology was set up by the incubation of Torpedo marmorata electrocyte membranes rich in nAChRs with BSA tryptic digests (>100 peptides) doped by small amounts of known nAChRs ligands (alpha-conotoxins). Peptides that bind to the receptors were purified and analyzed by MALDI-TOF/TOF mass spectrometry which revealed an enrichment of alpha-conotoxins in membrane-containing fractions. This result exhibits the binding of alpha-conotoxins to nAChRs. Negative controls were performed to demonstrate the specificity of the binding. The usefulness and the power of the methodology were also investigated for a discovery issue. The workflow was then applied to the screening of Conus ermineus crude venom, aiming at characterizing new nAChRs ligands from this venom, which has not been extensively investigated to date. The methodology validated our experiments by allowing us to bind two alpha-conotoxins (alpha-EI and alpha-EIIA) which have already been described as nAChRs ligands. Moreover, a new conotoxin, never described to date, was also captured, identified and sequenced from this venom. Classical pharmacology tests by radioligand binding using a synthetic homologue of the toxin confirm the activity of the new peptide, called alpha-EIIB. The Ki value of this peptide for Torpedo nicotinic receptors was measured at 2.2 +/- 0.7 nM121138/ field[33]: Not in File :?cXEizadi-Mood, N. Aboofazeli, E. Hajhashemi, V. Gheshlaghi, F. Badri, S. Sabzghabaee, A.M.2016bEffect of intravenous midazolam on cardiac parameters in acute tricyclic antidepressants poisoning195-200ARYA Atherosclerosis124ACUTE ANTIDEPRESSANTS BLOOD BLOOD PRESSURE CARDIAC CARDIOVASCULAR Cardiovascular toxicity central nervous system CLINICAL DEXTROSE dose DRUG drugs FATAL HEART Heart Rate HOSPITAL HOSPITAL ADMISSION INFUSION INTENSIVE CARE INTRAVENOUS IS LOADING DOSE maintenance MANAGEMENT method methods MIDAZOLAM MORBIDITY MORTALITY NO outcome PATIENT PLACEBO POISONING Reduction RESPIRATORY STATUS STUDY TACHYCARDIA THERAPY Time Toxicities TOXICITY TRIAL TRICYCLIC ANTIDEPRESSANTS7/2016CBACKGROUND: Midazolam is commonly and safely used in poisoning management and intensive care for the control of agitated poisoned patients. Despite the introduction of newer and safer antidepressants, tricyclic antidepressants (TCAs) are still prescribed and used in many countries due to their cost-effectiveness. Severe morbidity and mortality associated with these drugs arises largely from their well-documented cardiovascular toxicity. In this study we aimed to investigate the probable effect of midazolam on some hemodynamic indices in TCAs-poisoned patients. METHODS: In this clinical trial, we have evaluated some cardiovascular and hemodynamic indices of 100 TCAs-poisoned patients whom were randomly allocated for receiving midazolam with a first loading dose of 0.1 mg/kg (2 mg/minute) followed by a 6-hour maintenance infusion of 0.1 mg/kg/h of the drug in dextrose-saline (3.33% of dextrose and 0.33% of NaCl) or placebo (dextrose-saline infusion without midazolam). Pulse rate, systolic/diastolic blood pressure, respiratory rate, neurologic status and the outcome of therapy for all patients were recorded at the time of admission and hourly for the next 6 hours. RESULTS: There was a statistically significant reduction in the heart rate of the midazolam treated group after the first hour of hospital admission. There were no significant differences in the respiratory rate, central nervous system manifestations and other indices between the two groups. CONCLUSION: Midazolam may reduce tachycardia (and its fatal consequences) in the first hour of admission in TCAs-poisoned patients120697+ field[33]: Not in File ?dEkpenyong, C.E. Asuquo, A.E.2017iRecent advances in occupational and environmental health hazards of workers exposed to gasoline compounds1-26GInternational Journal of Occupational Medicine and Environmental Health301UACID ADENOSINE Adverse ADVERSE EFFECTS Affect ANTIOXIDANT BILE case CELL CYTOCHROME CYTOCHROME P450 DATA DETECTION DNA ENVIRONMENTAL ENZYME EXPOSURE GASOLINE HAZARD HEALTH Health hazard health hazards Health risk Health risks HUMAN Humans ILLNESS impact INDUCTION INFORMATION INTERACTION Knowledge LIPID MECHANISM Mechanisms MEMBRANE METABOLITE Metabolites NEUROTRANSMITTER NITRIC OXIDE NO OCCUPATIONAL OIL OXIDATIVE STRESS OXYGEN P450 PETROL PROTEIN proteins Regulatory RESEARCH REVIEW RISK ROS SAFETY SPECIES STRESS SURVEILLANCE TECHNIQUE THERAPEUTIC Toxicities TOXICITY Toxicity profile workers 2/21/2017The impact of health and environmental hazards, associated with the constituents of gasoline, on occupationally exposed workers has been recorded over the past few decades. However, the scientific literature on their pathogenic potential remains incomplete, which could affect the current understanding of the associated health risks. This review provides current information based on recently improved research techniques to evaluate gasoline toxicity profiles for humans. Our current knowledge provides insight into the intricate mechanism of gasoline-induced adverse effects, including the formation of reactive metabolites via bio-activation and subsequent generation of reactive oxygen species (ROS) and oxidative stress, which are involved in multiple mechanisms that are central to the aetiology of gasoline-induced toxicity. These mechanisms include covalent binding to deoxyribonucleic acid (DNA), leading to oxidative damage, tumor-suppression gene activity, and activation of pro-oncogenes. Furthermore, it results in induction of autoimmunity and local inflammatory responses, disruption of multiple neurotransmitters and immune cell function, derangement of various enzyme activities (e.g., sodiumpotassium adenosine triphosphate (Na+/K+/ATPase) activity, cytochrome P450 (CYP450), nitric oxide synthase (NOS), antioxidant enzyme activities, etc.), conjugation of bile, and non-specific cell membrane interaction, leading to damage of the membrane lipid bilayer and proteins. Available data suggests that exposure to gasoline or gasoline constituents have the potential to cause different types of illnesses. The data highlights the need to maintain safety measures via suitable research, medical surveillance, regulatory control, life style modification, early detection, and intervention to minimize exposure and manage suspected cases. They also present novel opportunities to design and develop effective therapeutic strategies against gasoline-induced detrimental effects. Int J Occup Med Environ Health 2017;30(1):1-26121027* field[33]:,63255,0,2.html Not in File B?e[El Balkhi, S. Chaslot, M. Picard, N. Dulaurent, S. Delage, M. Mathieu, O. Saint-Marcoux, F.2017Characterization and identification of eight designer benzodiazepine metabolites by incubation with human liver microsomes and analysis by a triple quadrupole mass spectrometer'International Journal of Legal Medicine,online early: doi: 10.1007/s00414-017-1541-6not published, 16 Feb 178analysis ANALYTICAL Benzodiazepine BENZODIAZEPINES biological case Characterization CLINICAL CONCENTRATIONS Designer Benzodiazepine designer drug DESIGNER DRUGS DRUG drugs ETIZOLAM flubromazolam FORENSIC Forensic toxicology high resolution mass spectrometry HUMAN IDENTIFICATION IN VITRO Laboratories LABORATORY LIVER LORAZEPAM LORMETAZEPAM MASS SPECTROMETRY MECLONAZEPAM METABOLITE Metabolites MICROSOME MONITORING new psychoactive substance NOVEL PSYCHOACTIVE SUBSTANCES NPS POISONING POST MORTEM Post-mortem POSTMORTEM SPECTROMETRY STUDY TOXICOLOGY UHPLC UNIT URINE2/4/2017Designer benzodiazepines (DBZDs) have become of particular importance in the past few years. The metabolite monitoring of DBZD in biological fluids could be of great interest in clinical and forensic toxicology. However, DBZD metabolites are not known or not commercially available. The identification of some DBZD metabolites has been mostly explored by self-administration studies or by in vitro studies followed by high-resolution mass spectrometry. The question arose whether a unit resolution instrument could be efficient enough to allow the identification of DBZD metabolites. In this study, we used an in vitro experiment where eight DBZDs (diclazepam, flubromazepam, etizolam, deschloroetizolam, flubromazolam, nifoxipam, meclonazepam and clonazolam) were incubated with human liver microsomes (HLMs) and metabolite identification was carried out by using a UHPLC coupled to a QTRAP triple quadrupole linear iontrap tandem mass spectrometer system. Post-mortem samples obtained from a real poisoning case, involving deschloroetizolam and diclazepam, were also analysed and discussed. Our study using HLM allowed the identification of 26 metabolites of the 8 DBZDs. These were denitro-, mono- or di-hydroxylated and desmethyl metabolites. In the forensic case, diclazepam was not detected whereas its metabolites (lormetazepam and lorazepam) were present at high concentrations in urine. We also identified hydroxy-deschloroetizolam in urine, while the parent compound was not detected in this matrix. This supports the approach that LC coupled to a simple QTRAP could be used by laboratories to identify other not-known/not-commercialized new psychoactive substance (NPS) metabolites120717+ field[33]: Not in File B?fEltony, S.A. Abdelhameed, S.Y.2017Effect of chronic administration of sildenafil citrate (Viagra) on the histology of the retina and optic nerve of adult male rat Tissue Cell-online early: doi: 10.1016/j.tice.2017.01.006not published, 01 Mar 17ADULT As BLOOD CAPILLARY CELL CHRONIC CITRATE dose DRUG electron microscopy ENDOTHELIAL HISTOLOGY MALE Male rat men method methods microglia MICROSCOPY NERVE OCULAR Optic Nerve PATIENT RAT rats recovery retina SILDENAFIL THERAPEUTIC toxic TREATMENT use Wistar rat Wistar rats WITHDRAWAL2/5/2017BACKGROUND: Abnormal vision has been reported by 3% of patients treated with sildenafil citrate (Viagra). Although many men use Viagra for an extended period for treatment of erectile dysfunction, the implications of the long term-daily use of it on the retina and optic nerve are unclear. AIM OF THE WORK: To investigate the effect of chronic daily use of sildenafil citrate in a dose equivalent to men preferred therapeutic dose on the histology of the retina and optic nerve of adult male rat. MATERIAL & METHODS: Eighteen adult male Wistar rats were equally divided into three groups. Group I: control. Group II: treated with sildenafil citrate orally (10mg/kg/day) for 8 weeks. Group III (withdrawal): treated as group II and then left for 4 weeks without treatment. Specimens from the retina and optic nerve were processed for light and electron microscopy. RESULTS: In sildenafil citrate treated group, the retina and optic nerve revealed vacuolations and congested blood capillaries with apoptotic endothelial and pericytic cells, and thickened basal lamina. Caspase-3 (apoptotic marker) and CD31 (endothelial marker) expression increased. Glial cells revealed morphological changes: Muller cells lost their processes, activated microglia, astrocytic clasmatodendrosis, degenerated oligodendrocytes surrounded by disintegrated myelin sheathes of the optic nerve fibers. The retina and optic nerve of the withdrawal group revealed less vacuolations and congestion, and partial recovery of the glial cells. CONCLUSION: Chronic treatment with sildenafil citrate (Viagra) caused toxic effect on the structure of the retina and optic nerve of the rat. Partial recovery was observed after drug withdrawal121120, field[33]: Not in File ?g@XEom, S.-Y. Hwang, M.S. Lim, J.-A. Choi, B.-S. Kwon, H.-J. Park, J.-D. Kim, Y.-D. Kim, H.2017Exome-wide association study identifies genetic polymorphisms of C12orf51, MYL2, and ALDH2 associated with blood lead levels in the general Korean population11Environmental Health161uADULT Adverse ALCOHOL Alcohol consumption analysis ASSAY Association Behavior BLOOD Blood lead CALCIUM Consumption DATA determination DIETARY Environment EXPOSURE genetic HEALTH Health effects history HUMAN Humans Intake INTERACTION IS KOREAN LEAD LEVELS method methods NO OCCUPATIONAL OCCUPATIONAL EXPOSURE P POLYMORPHISM Population Regulation SCREENING STATUS STUDY toxic 2/17/2017&BACKGROUND: Lead (Pb) is a ubiquitous toxic metal present in the environment that poses adverse health effects to humans. Inter-individual variation in blood Pb levels is affected by various factors, including genetic makeup. However, limited data are available on the association between genetic variation and blood Pb levels. The purpose of this study was to identify the genetic markers associated with blood Pb levels in the Korean population. METHODS: The study subjects consisted of 1,483 healthy adults with no history of occupational exposure to Pb. We measured blood Pb levels and calculated probable daily intake of Pb according to dietary data collected using 24-hour recall. We conducted exome-wide association screening using Illumina Human Exome-12v1.2 platform (n = 500) and a replication analysis using VeraCode Goldengate assay (n = 1,483). RESULTS: Among the 244,770 single nucleotide polymorphisms (SNPs) tested, 12 SNPs associated with blood Pb level were identified, with suggestive significance level (P < 1 x 10-4). In the Goldengate assay for replication, three SNPs (C12orf51 rs11066280, MYL2 rs12229654, and ALDH2 rs671) were associated with statistically suggestively significant differences in blood Pb levels. When stratified by drinking status, a potential association of C12orf51 rs11066280, MYL2 rs12229654, and ALDH2 rs671 with blood Pb level was observed only in drinkers. A marginally significant gene-environment interaction between ALDH2 rs671 and alcohol consumption was observed in relation to blood Pb levels. The effects of the three suggestively significant SNPs on blood Pb levels was dependent on daily calcium intake amounts. CONCLUSIONS: This exome-wide association study indicated that C12orf51 rs11066280, MYL2 rs12229654, and ALDH2 rs671 polymorphisms are linked to blood Pb levels in the Korean population. Our results suggest that these three SNPs are involved in the determination of Pb levels in Koreans via the regulation of alcohol drinking behavior, and that their negative effects may be compensated by appropriate calcium intake120983+ field[33]: Not in File B?hGEstrada-Gómez, S. Gomez-Rave, L. Vargas-Muñoz, L. van der Meijden, A.2017Characterizing the biological and biochemical profile of six different scorpion venoms from the Buthidae and Scorpionidae familyToxicon0online early: doi: 10.1016/j.toxicon.2017.02.007not published, 01 Mar 17Africa analysis ANTIMICROBIAL biological CELL family ION CHANNEL Metalloproteinase method methods NO P PROTEIN proteins SCORPION scorpion venom SPECIES STUDY t toxin TOXINS Venom 2/13/2017The objective of this study was to characterize a selection of six different scorpion venoms using biological and biochemical methods, including a preliminary MS/MS and a post-translational modifications analysis. Despite the diversity of scorpion species of medical importance in Africa and Colombia, the venoms of these arachnids have been poorly studied in these two regions. We report the biochemical, electrophoretic, chromatographic profile, internal peptide sequences with a post-translational modification report, and a preliminary antitumor activity of five different scorpions of the Buthidae family, Androctonus amoreuxi, Babycurus jacksoni, Grosphus grandidieri, Hottentotta gentili and Tityus fuhrmanni, and one of the Scorpionidae family Pandinus imperator. No L-amino oxidase activity was detected in the evaluated venoms. Proteolytic activity using azocasein was detected only in G. grandidieri and P. imperator, indicating the possible presence of metalloproteinases in these two venoms. Proteolytic activity using NOBA was detected in all venoms indicating the presence of serine-proteinases. Phospholipase A2 activity was detected in the venoms of P. imperator, G. grandidieri, H. gentili and A. amoreuxi, with P. imperator venom being the most active. All venoms analyzed contained defensin-like proteins, alpha toxins, metalloproteinases, neuropeptides, DBP affecting ion channels, DBP with antimicrobial activity, among others. Venoms from P. imperator, G. grandidieri and T. fuhrmanni showed a dose-dependent cytotoxic activity over MCF-7 cells. Only two isolated RP-HPLC fractions from P. imperator and T. fuhrmanni showed cytotoxic activity over MCF-7. No cytotoxic activity was found in the venoms from A. amoreuxi, B. jacksoni, and H. gentili121136/ field[33]: Not in File CB?i8Fabresse, N. Grassin-Delyle, S. Etting, I. Alvarez, J.C.2017Detection and quantification of 12 anabolic steroids and analogs in human whole blood and 20 in hair using LC-HRMS/MS: application to real cases'International Journal of Legal Medicine,online early: doi: 10.1007/s00414-017-1552-3not published, 01 Mar 17=ANABOLIC STEROID Anabolic steroids analog analysis ANALYTICAL APCI BLOOD case CHROMATOGRAPHY DETECTION HAIR HEPTANE high resolution mass spectrometry HUMAN Human whole blood internal standard Liquid chromatography MASS SPECTROMETRY method pH PHOSPHATE quantification SPECTROMETRY STANOZOLOL STEROID TESTOSTERONE URINE 2/24/2017We developed and validated a method to detect and quantify 12 anabolic steroids in blood (androstenedione, dihydrotestosterone, boldenone, epitestosterone, mesterolone, methandienone, nandrolone, stanozolol, norandrostenedione, tamoxifene, testosterone, trenbolone) and eight more in hair samples (nandrolone phenylpropionate, nandrolone decanoate, testosterone propionate, testosterone benzoate, testosterone cypionate, testosterone decanoate, testosterone phenylpropionate, testosterone undecanoate) using liquid chromatography coupled to high-resolution mass spectrometry. This method used a benchtop Orbitrap mass spectrometer operating with an APCI probe under positive ionization mode. Analysis was realized in full scan experiment with a nominal resolving power of 140,000. After addition of the internal standard (testosterone-D3) and incubation in phosphate buffer pH = 5 for hair, 200 muL of blood and 30 mg of hair samples were extracted with heptane. LOQ and LOD were determined at 5 and 1 ng mL-1 in whole blood and 10 to 100 pg mg-1 and 2 to 20 pg mg-1 in hair according to the compounds, respectively. The method was linear in the 5-1000 ng mL-1 range in whole blood and between 10 or 100 pg mg-1 and 1000 pg mg-1 in hair with correlation coefficients >0.99, and intra- and inter-day accuracy and precision were <14.8% for all compounds except for some esters in hairs (<19.9%) probably due to an important matrix effect for these compounds. This sensitive and specific method to detect anabolic steroids has been successfully applied to two real cases, for which various anabolic steroids in whole blood, urine, and hair were identified and quantified121025+ field[33]: Not in File B?jFaiz, M.A. Ahsan, M.F. Ghose, A. Rahman, M.R. Amin, R. Hossain, M. Tareq, M.N. Jalil, M.A. Kuch, U. Theakston, R.D. Warrell, D.A. Harris, J.B.2017Bites by the Monocled Cobra, Naja kaouthia, in Chittagong division, Bangladesh: epidemiology, clinical features of envenoming and management of 70 identified cases/American Journal of Tropical Medicine & Hygiene(online early: doi: 10.4269/ajtmh.16-0842not published, 16 Feb 17Adverse adverse reactions ANTICHOLINESTERASE ANTIVENOM case CLINICAL COBRA College DRUG EDROPHONIUM envenoming EPIDEMIOLOGY EYE First Aid HEALTH HOSPITAL LIMB MANAGEMENT NECROSIS NEOSTIGMINE NEUROTOXICITY pain PATIENT REACTIONS Rural SERUM snake bite Snakes SPECIES STUDY use Venom 1/30/2017We describe 70 cases of monocled cobra (Naja kaouthia) bite admitted to Chittagong Medical College Hospital, Bangladesh. The biting snakes were identified by examining the dead snake and/or detecting N. kaouthia venom antigens in patients' serum. Bites were most common in the early morning and evening during the monsoon (May-July). Ligatures were routinely applied to the bitten limb before admission. Thirty-seven patients consulted traditional healers, most of whom made incisions around the bite site. Fifty-eight patients experienced severe neurotoxicity and most suffered swelling and pain of the bitten limb. The use of an Indian polyvalent antivenom in patients exhibiting severe neurotoxicity resulted in clinical improvement but most patients experienced moderate-to-severe adverse reactions. Antivenom did not influence local blistering and necrosis appearing in 19 patients; 12 required debridement. Edrophonium significantly improved the ability of patients to open the eyes, endurance of upward gaze, and peak expiratory flow rate suggesting that a longer-acting anticholinesterase drug (neostigmine) could be recommended for first aid. The study suggested that regionally appropriate antivenom should be raised against the venoms of the major envenoming species of Bangladesh and highlighted the need to improve the training of staff of local medical centers and to invest in the basic health infrastructure in rural communities120694' field[33]: Not in File ?k%Fakhar, A. Abdul, A.U.B. Nadeem, A.A.20169Endosulfan toxicity: is seizure a criterion for mortality17-209Indian Internet Journal of Forensic Medicine & Toxicology143-4^Age analysis Association Attention BLOOD Blood samples case central nervous system CHLORINATED CLINICAL College DATA DIAGNOSIS ENDOSULFAN FEMALE Guidelines history HOSPITAL INSECTICIDE IS Laboratories LABORATORY LEGAL MALE MORBIDITY MORTALITY NO oc P PATIENT POISONING Retrospective study seizure SEIZURES STUDY suicidal Toxicities TOXICITY TREATMENT2016Endosulfan is a chlorinated insecticide that causes Central Nervous System hyperstimulation state. Mortality and morbidity rates are high and there is no specific treatment for this toxicity. A retrospective study of endosulfan poisoning cases was conducted in the National Institute of Medical Science Medical College & Hospital, Jaipur, Rajasthan to assess endosulfan poisoning cases and to find out the association between seizures and mortality. Data was retrieved from clinical records and laboratory files. Diagnosis was based on history and clinical findings. Blood samples of all the patients were sent for toxicological analysis. Out of 42 cases, 36 (85.71%) were males and 6 (14.29%) were females. Mean age of the victims was 34 years. 76.19% patients were farmers. The most common mode of poisoning was suicidal (95.24%). The total mortality rate was 78.57%. Generalised tonic–clonic (GTC) type seizure was recorded in 83.33% cases. The association between mortality and GTC seizure was found to be significant (p < 0.0001). This study seeks special attention from government and implementation of strict legal guidelines to curb the menace of endosulfan poisoning.1209270 field[33]: Not in File ?l(Farahani, M.V. Soroosh, D. Marashi, S.M.2016{Thoughts on the current management of acute aluminum phosphide toxicity and proposals for therapy: an evidence-based review724-730(Indian Journal of Critical Care Medicine2012OACID-BASE DISTURBANCE ACUTE acute poisoning Acute toxicity agent ALUMINIUM ALUMINIUM PHOSPHIDE aluminum BICARBONATE BLOOD BLOOD PRESSURE CARDIAC case CLINICAL CRITICAL CARE CYTOCHROME CYTOCHROME C OXIDASE effectiveness EVALUATION EVIDENCE-BASED FAILURE Frequency GASTRIC GASTRIC LAVAGE HUMAN INFORMATION Inhibition IS IV Knowledge LAVAGE MANAGEMENT MECHANISM Medicine MORTALITY PATIENT POISONING PROTOCOL Protocols Randomized trial RESUSCITATION REVIEW SODIUM SODIUM BICARBONATE STUDY suicidal SURVIVAL THERAPY Toxicities TOXICITY TOXICOKINETIC toxicokinetics TREATMENT TRIAL VASCULAR WEIGHT12/2016The majority of aluminum phosphide (ALP) toxicity cases are suicidal attempts. Despite advances in critical care medicine, the mortality rate of ALP remains very high. Unfortunately, knowledge on the toxicokinetics of ALP is very low. An obsolete idea was proposed that inhibition of complex IV of cytochrome C oxidase is responsible for multiorgan dysfunction. However, based on human studies, this effect might be insignificant. Thus, a novel idea proposes that the main mechanism might be vascular wall integrity disruption. The low frequency of acute toxicity and unanswered questions about the toxicokinetics and toxicodynamics has led to leaden advances of novel treatments. The aim of this review was to evaluate problems regarding current treatment protocols and propose new ideas based on updated information. For this purpose, we reviewed all available articles on the management of ALP poisoning published to date. Considering failure of conventional therapies on maintaining systolic blood pressure, correcting acid-base disturbances, and support cardiac function, the previous treatment protocols have been overruled. However, repudiate of conventional treatments in this deadly condition is not without penalties for the health-care provider. The introduction of new therapies including refuse of gastric lavage with water-soluble compounds, administration of a high molecular weight colloidal solution for fluid resuscitation and termination using sodium bicarbonate, and vasoactive agents has been prospected to improve patient survival. This protocol is in early clinical evaluation; nevertheless, it appears to improve patient's survival; hence, future randomized trials should be performed to support their effectiveness120718* field[33]: year=2016 volume=20 issue=12 spage=724 epage=730 aulast=Farahani Not in File]?m4Farsalinos, K. Gillman, G. Kistler, K. Yannovits, N.2017]Comment on "Flavoring compounds dominate toxic aldehyde production during e cigarette vaping" 2491-2492"Environmental Science & Technology514[ALDEHYDES CIGARETTE E CIGARETTE E Cigarettes E-CIGARETTE e-Cigarettes e-liquid LETTER toxic2/7/2017120878) field[33]: Not in File B?nZFernandes-Cunha, G.M. Fialho, S.L. da Silva, G.R. Silva-Cunha, A. Zhao, M. Behar-Cohen, F.2017QOcular safety of intravitreal clindamycin hydrochloride released by PLGA implants Pharm Res,online early: doi: 10.1007/s11095-017-2118-2not published, 01 Mar 17=ACID As Attention CELL CLINDAMYCIN CLINICAL cytokine CYTOKINES DRUG EXPOSURE EYE GENE EXPRESSION HUMAN IL-6 IMMUNOFLUORESCENCE IN VIVO INFECTION INFLAMMATION INTRAOCULAR IS LEVELS method methods neuron NO Observation OCULAR RABBIT RAT retina SAFETY STUDY THERAPEUTIC TISSUE Toxicities TOXICITY TOXOPLASMOSIS TREATMENT 2/21/2017^BACKGROUND: Drug ocular toxicity is a field that requires attention. Clindamycin has been injected intravitreally to treat ocular toxoplasmosis, the most common cause of eye posterior segment infection worldwide. However, little is known about the toxicity of clindamycin to ocular tissues. We have previously showed non intraocular toxicity in rabbit eyes of poly(lactic-co-glycolic acid) (PLGA) implants containing clindamycin hydrochloride (CLH) using only clinical macroscotopic observation. In this study, we investigated the in vivo biocompatibility of CLH-PLGA implants at microscotopic, cellular and molecular levels. METHODS: Morphology of ARPE-19 and MIO-M1 human retinal cell lines was examined after 72 h exposure to CLH-PLGA implant. Drug delivery system was also implanted in the vitreous of rat eyes, retinal morphology was evaluated in vivo and ex vivo. Morphology of photoreceptors and inflammation was assessed using immunofluorescence and real-time PCR. RESULTS: After 72 h incubation with CLH-PLGA implant, ARPE-19 and MIO-M1 cells preserved the actin filament network and cell morphology. Rat retinas displayed normal lamination structure at 30 days after CLH-PLGA implantation. There was no apoptotic cell and no loss in neuron cells. Cones and rods maintained their normal structure. Microglia/macrophages remained inactive. CLH-PLGA implantation did not induce gene expression of cytokines (IL-1beta, TNF-alpha, IL-6), VEGF, and iNOS at day 30. CONCLUSION: These results demonstrated the safety of the implant and highlight this device as a therapeutic alternative for the treatment of ocular toxoplasmosis121089+ field[33]: Not in FileB?o Fernando, I.2017rPredicting serum drug level using the principles of pharmacokinetics after an overdose: a case of lithium overdoseAustralas. Psychiatry+online early: doi: 10.1177/1039856216689624not published, 28 Feb 17}case CLINICAL DRUG drug overdose IS KINETICS LEVELS LITHIUM method OVERDOSE PAPER pharmacokinetic PHARMACOKINETICS SERUM Time2/1/2017wOBJECTIVE: In cases of drug overdose, clinicians often find it challenging to predict serum drug level and decide the optimum time for recommencing the overdosed drug. METHOD: This paper describes how to predict serum drug level using the principles of pharmacokinetics. RESULTS: The proposed method and recommencement of the overdosed drug is demonstrated using a clinical case of lithium overdose. CONCLUSION: The proposed method can assist clinicians in predicting serum drug levels and deciding the optimum time for recommencing the overdosed drug safely. Therefore, it may reduce unnecessary repeat serum drug level procedures120856* field[33]: Not in File?pFerreiro, S.F. Vilarino, N. Carrera, C. Louzao, M.C. Santamarina, G. Cantalapiedra, A.G. Cifuentes, J.M. Vieira, A.C. Botana, L.M.2017CSubacute immunotoxicity of the marine phycotoxin yessotoxin in rats74-80Toxicon129>As Biomarker BIOMARKERS Content cytokine DINOFLAGELLATES dose EXPOSURE FOOD Food safety HEALTH HUMAN Human health IL-6 IMMUNE SYSTEM IMMUNOTOXICITY INJECTION INTOXICATION INTRAPERITONEAL IS LEVELS NO Organs POISONING Population RAT rats Reduction SAFETY SHELLFISH SPLEEN STUDY SUBACUTE Target organs thymus Time TISSUE 2/14/2017Yessotoxin (YTX) is a marine phycotoxin produced by dinoflagellates and accumulated in filter feeding shellfish. YTX content in shellfish is regulated by many food safety authorities to protect human health, although currently no human intoxication episodes have been unequivocally related to YTX presence in food. The immune system has been proposed as one of the target organs of YTX due to alterations of lymphoid tissues and cellular and humoral components. The aim of the present study was to explore subacute immunotoxicity of YTX in rats by evaluating the haematological response, inflammatory cytokine biomarkers and the presence of YTX-induced structural alterations in the spleen and thymus. The results showed that repeated administrations of YTX caused a decrease of lymphocyte percentage and an increase of neutrophil counts, a reduction in interleukine-6 (IL-6) plasmatic levels and histopathological splenic alterations in rats after four intraperitoneal injections of YTX at doses of 50 or 70 mug/kg that were administered every 4 days along a period of 15 days. Therefore, for the first time, subacute YTX-immunotoxicity is reported in rats, suggesting that repeated exposures to low amounts of YTX might also suppose a threat to human health, especially in immuno-compromised populations121135/ field[33]: Not in File ,B?qFettiplace, M.R. McCabe, D.J.2017_Lipid emulsion improves survival in animal models of local anesthetic toxicity: a meta-analysisClinical Toxicology0online early: doi: 10.1080/15563650.2017.1288911not published, 03 Mar 17TAIRWAY anaesthetic ANAESTHETICS analysis Anesthetic ANIMAL animal models As BUPIVACAINE CLINICAL CLINICAL TOXICOLOGY DATA DEATH DISTRIBUTION EXPERIMENTAL LIPID Lipid emulsion LIPID EMULSION THERAPY Meta-analysis MODEL Odds Ratio P PUBLICATION REVIEW STUDY SURVIVAL systematic review TEST THERAPY Toxicities TOXICITY TOXICOLOGY TREATMENT use 2/17/2017Introduction: The Lipid Emulsion Therapy workgroup, organized by the American Academy of Clinical Toxicology, recently conducted a systematic review, which subjectively evaluated lipid emulsion as a treatment for local anesthetic toxicity. We re-extracted data and conducted a meta-analysis of survival in animal models.Methods: We extracted survival data from 26 publications and conducted a random-effect meta-analysis based on odds ratio weighted by inverse variance. We assessed the benefit of lipid emulsion as an independent variable in resuscitative models (16 studies). We measured Cochran's Q for heterogeneity and I2 to determine variance contributed by heterogeneity. Finally, we conducted a funnel plot analysis and Egger's test to assess for publication bias in studies.Results: Lipid emulsion reduced the odds of death in resuscitative models (OR =0.24; 95%CI: 0.1–0.56, p = .0012). Heterogeneity analysis indicated a homogenous distribution. Funnel plot analysis did not indicate publication bias in experimental models.Discussion: Meta-analysis of animal data supports the use of lipid emulsion (in combination with other resuscitative measures) for the treatment of local anesthetic toxicity, specifically from bupivacaine. Our conclusion differed from the original review. Analysis of outliers reinforced the need for good life support measures (securement of airway and chest compressions) along with prompt treatment with lipid121152/ field[33]: Not in File (B?rFinkelstein, Y. Macdonald, E.M. Gonzalez, A. Sivilotti, M.L. Mamdani, M.M. Juurlink, D.N. Canadian Drug Safety And Effectiveness Research Network (CDSERN),2017;Overdose risk in young children of women prescribed opioids Pediatrics)online early: doi: 10.1542/peds.2016-2887not published, 01 Mar 17ADDICTION Aged analgesic ANTIDEPRESSANTS As Canada case case-control CHILDREN CODEINE DEATH Deaths DRUG harm HOSPITAL METHADONE method methods MOTHERS NO Odds Ratio OPIOID opioid addiction Opioid overdose Opioids outcome OVERDOSE OXYCODONE PAEDIATRIC PRESCRIBING RISK STUDY WHO WOMEN 2/20/2017BACKGROUND AND OBJECTIVE: Over the past 20 years, the prescribing of opioids has increased dramatically in North America, with parallel increases in opioid addiction, overdose, and associated deaths. We examined whether young children of women prescribed opioids were at increased risk of opioid overdose. METHODS: We conducted a population-based, nested case control study in Ontario, Canada, between 2002 and 2015. We identified children aged ?Flint, R.B. Mian, P. van der Nagel, B. Slijkhuis, N. Koch, B.C.2017Quantification of acetaminophen and its metabolites in plasma using UPLC-MS: doors open to therapeutic drug monitoring in special patient populationsTherapeutic Drug Monitoring/online early: doi: 10.1097/FTD.0000000000000379not published, 28 Feb 17ACETAMINOPHEN ACETATE ACID AMMONIA ANALYTICAL ANTIDOTE As author DOSAGE DRUG Europe EXPOSURE Fever FOOD FORMIC ACID Guidelines HUMAN human plasma INJECTION internal standard INTOXICATION IS Knowledge LEAD MASS SPECTROMETRY METABOLITE Metabolites METHANOL method methods MONITORING pain PARACETAMOL PATIENT PLASMA Population quality quality control quantification RESEARCH safe SPECTROMETRY THERAPEUTIC Therapeutic drug monitoring toxic TREATMENT UNITED STATES UPLC UPLC-MS/MS US Volume WATER2/6/2017BACKGROUND: Acetaminophen (APAP, paracetamol) is the most commonly used drug for pain and fever in both the United States and Europe and considered safe when used at registered dosages. Nevertheless, differences between specific populations lead to remarkable changes in exposure to potentially toxic metabolites. Furthermore, extended knowledge is required on metabolite formation following intoxication, to optimize antidote treatment. Therefore, the authors aimed to develop and validate a quick and easy analytical method for simultaneous quantification of APAP, APAP-glucuronide, APAP-sulfate, APAP-cysteine, APAP-glutathione, APAP-mercapturate, and protein-derived APAP-cysteine in human plasma by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-MS/MS). METHODS: The internal standard was APAP-D4 for all analytes. Chromatographic separation was achieved with a reversed-phase Acquity UPLC HSS T3 column with a runtime of only 4.5 minutes per injected sample. Gradient elution was performed with a mobile phase consisting of ammonium acetate, formic acid in Milli-Q ultrapure water or in methanol at flow rate of 0.4 mL/min. RESULTS: A plasma volume of only 10 microL was required to achieve both adequate accuracy and precision. Calibration curves of all six analytes were linear. All analytes were stable for at least 48 hours in the autosampler; the high quality control of APAP-glutathione was stable for 24 hours. The method was validated according to the US Food and Drug Administration guidelines. CONCLUSIONS: This method allows quantification of acetaminophen and six metabolites, which serves purposes for research, as well as therapeutic drug monitoring (TDM). The advantage of this method is the combination of minimal injection volume, a short runtime, an easy sample preparation method, and the ability to quantify acetaminophen and all six metabolites120923. field[33]: Not in File B?t&Folletti, I. Siracusa, A. Paolocci, G.2017$Update on asthma and cleaning agents2Current Opinion in Allergy and Clinical Immunology/online early: doi: 10.1097/ACI.0000000000000349not published, 16 Feb 17pagent ALDEHYDES As ASTHMA case CASE REPORT case reports Case-report DISEASE DISINFECTANT disinfectants DOMESTIC EPIDEMIOLOGY evidence EXPOSURE FRAGRANCE Frequency Healthcare workers immunological INFORMATION INTERACTION IS MECHANISM men Occupation OCCUPATIONAL OCCUPATIONAL EXPOSURE PREVENTION RESPIRATORY RESPIRATORY SYMPTOMS REVIEW RISK SYMPTOMS WEIGHT WOMEN workers 1/30/2017wPURPOSE OF REVIEW: Asthma due to cleaning products has been known for 20 years, and the interest in this topic is still large because of the number of cleaning workers with respiratory problems. In this review, we sought to highlight the most recent findings on the relationship between exposure to cleaning products and asthma and to summarize the specific literature published between 2013 and 2016. RECENT FINDINGS: Women are confirmed as most of workers exposed to cleaning products and have a higher frequency than men of work-related respiratory symptoms and diseases. Many cases of asthma due to cleaning products occur in healthcare occupations. The increased risk of asthma has been shown to be related to the number of years in the job and to early life disadvantage. Recent evidence suggests that predisposition to adult-onset asthma may be related to interaction between genes and occupational exposure to low-molecular weight agents/irritants. There is some evidence that an irritant mechanism is more common, although several case reports showed animmunologic mechanism (e.g. disinfectants, amine compounds, aldehydes and fragrances). SUMMARY: The review updated recent findings on epidemiology, cleaning agents and their mechanism, and prevention of asthma due to cleaning agents. This article provides new information on the level of exposure, which is still high in professional cleaners and even more in domestic cleaners, and on the frequency of asthma in professional and domestic cleaners. An irritant mechanism is more common, although an immunological mechanism is possible, especially in healthcare workers exposed to disinfectants120719. field[33]: Not in FileB?u2Ford, B.M. Tai, S. Fantegrossi, W.E. Prather, P.L.2017/Synthetic pot: not your grandfather's marijuana"Trends in Pharmacological Sciences-online early: doi: 10.1016/ published, 28 Feb 17"ADOLESCENT Adolescents Adverse ADVERSE EFFECTS As CANNABINOID cannabinoids CANNABIS DESIGNER DRUGS DETECTION DRUG Europe evidence Ingredient K2 LEGAL MARIJUANA MECHANISM Mechanisms MILITARY NOVEL PSYCHOACTIVE SUBSTANCES RECEPTORS safe SPICE SYNTHETIC CANNABINOID Synthetic cannabinoids TEST 1/27/2017In the early 2000s in Europe and shortly thereafter in the USA, it was reported that 'legal' forms of marijuana were being sold under the name K2 and/or Spice. Active ingredients in K2/Spice products were determined to be synthetic cannabinoids (SCBs), producing psychotropic actions via CB1 cannabinoid receptors, similar to those of Delta9-tetrahydrocannabinol (Delta9-THC), the primary active constituent in marijuana. Often abused by adolescents and military personnel to elude detection in drug tests due to their lack of structural similarity to Delta9-THC, SCBs are falsely marketed as safe marijuana substitutes. Instead, SCBs are a highly structural diverse group of compounds, easily synthesized, which produce very dangerous adverse effects occurring by, as of yet, unknown mechanisms. Therefore, available evidence indicates that K2/Spice products are clearly not safe marijuana alternatives120926, field[33]: Not in File ?vForrester, M.B.2017sComparison of poisonings managed at military and Veterans Administration hospitals reported to Texas poison centers50-55 Public Health142ZAge Aged ALCOHOL analgesic ANALGESICS analysis ANTIDEPRESSANTS case CLINICAL COMPARISON DATA DISTRIBUTION EDUCATION EPIDEMIOLOGY EXPOSURE HEALTH HOSPITAL INFORMATION IS MALE MANAGEMENT method methods MILITARY PATIENT Poison poison centers POISONING poisonings Population PREVENTION PUBLIC PUBLIC HEALTH STUDY SUICIDE Texas TREATMENT unintentional2017\Objectives There is little information on poisonings managed at military and Veterans Administration (VA) hospitals. This investigation described and compared poisonings reported to Texas poison centers that were managed at military and VA hospitals. Study design Retrospective analysis of poison centre data. Methods Cases were poisonings among patients aged 18 years or more reported to Texas poison centers during 2000-2015 where management occurred at a military or VA hospital. The distribution of exposures for various demographic and clinical factors was determined for military and veterans hospitals and comparisons were made between the two groups. Results There were 4353 and 1676 poisonings managed at military and VA hospitals, resepctively. Males accounted for 50.5% of the military hospital patients and 84.9% of the VA hospital patients. The mean age for military hospital patients was 31 years and for VA hospital patients was 50 years. The proportion of poisonings managed at military hospitals and VA hospitals, respectively, were intentional (70.0% vs 64.1%), particularly suspected attempted suicide (57.3% vs 47.7%), and unintentional (25.0% vs 30.5%). More than one substance was reported in 37.7% of military and 33.2% of VA hospital poisonings. The most commonly reported substance categories for poisonings managed at military and VA hospitals, respectively, were analgesics (28.4% vs 19.7%), sedatives/hypnotics/antipsychotics (24.7% vs 23.4%), antidepressants (18.7% vs 19.7%) and alcohol (11.3% vs 10.6%). Conclusions A number of differences were observed between poisonings managed at military and VA hospitals. These differing patterns of poisonings may need to be taken into account in the education, prevention and treatment of poisonings at these hospitals and among the populations they serve. Copyright © 2016 The Royal Society for Public Health120834, field[33]: Not in FilepB?wFøreid, S. Gadeholt, G.2017Beta-hydroxybutyrate and pyroglutamate can be included in a rapid GC-MS screening method for differential diagnosis of metabolic acidosis;Scandinavian Journal of Clinical & Laboratory Investigation0online early: doi: 10.1080/00365513.2016.1278261not published, 16 Feb 17ACID ACIDOSIS ACUTE ALCOHOLIC ANALYTICAL ANION GAP CLINICAL CYSTEINE deficiency DIAGNOSIS Ethylene ETHYLENE GLYCOL GA GAP GAS GC-MS GLYCOLIC ACID IS KETOACIDOSIS METABOLIC ACIDOSIS method POISONING SCREENING2/2/2017&A rapid gas chromatographic mass spectrometric method for measuring anions associated with acute anion gap metabolic acidosis is described. The method is an extension of a previous method. The method quantifies glycolic acid, beta-hydroxybutyric acid with good linearity and pyroglutamic acid with a reproducible curvature relation between 1 and 20 mmol/L and can help the clinician distinguish effectively between ethylene glycol poisoning, alcoholic and diabetic ketoacidosis and cysteine deficiency so early that it will have clinical consequences120720/ field[33]: Not in File \B?xQFrancischi, J.N. Frade, T.I.C. de Almeida, M.P.A. de Queiroz, B.F.G. Bakhle, Y.S.2017gKetamine-xylazine anaesthesia and orofacial administration of substance P: a lethal combination in rats Neuropeptides-online early: doi: 10.1016/j.npep.2017.01.003not published, 28 Feb 17 5-HT ADULT Anaesthesia anaesthetic ANIMAL Animals ANTAGONIST As COMPARISON DEATH Deaths dose EXPERIMENTAL HISTAMINE INJECTION INTRAORAL IS ISOFLURANE KETAMINE lethal lethality MALE NO OEDEMA P PIZOTIFEN PYRILAMINE RAT rats TISSUE use WHO Wistar rat Wistar rats XYLAZINE 1/23/2017BACKGROUND AND AIMS: Ketamine+xylazine mixture is a widely used anaesthetic in animal experiments. In rats anaesthetized with this mixture, we have shown that injection of carrageenan, a standard proinflammatory stimulus, into the cheek (intra-oral injection) induced oedema. A likely mediator of this oedema is substance P (SP), a major transmitter of sensory nerves in orofacial tissue. We have assessed the effects of intra-oral injection of SP in rats. EXPERIMENTAL APPROACH: SP (50-1mug per rat) was injected intra-orally in male adult Holtzman or Wistar rats, anaesthetized with ketamine+xylazine. For comparison, histamine (50mug) and 5-HT (5mug) were similarly injected. Antagonists of SP (SR140333, 2mg/kg), of histamine (pyrilamine, 2mg/kg) or of 5-HT (pizotifen, 2mg/kg) were subcutaneously (s.c.) injected, 30min before the corresponding agonist. Oedema in the cheek was assessed by measuring tissue thickness with calipers. RESULTS: Intra-oral injection of SP (1-50mug per rat) in Holtzman or Wistar rats anaesthetized with ketamine+xylazine induced, dose-dependently, death within 15min, accompanied by signs of excessive salivation. Rats pretreated with SR140333 were protected against SP-induced lethality and the excessive salivation. However, intra-oral injection of either histamine or 5-HT did not induce death, only a characteristic cheek oedema. These doses of SP injected into the hindpaws of conscious Holtzman and Wistar rats only induced oedema with no deaths. In rats anaesthetized with inhaled isoflurane, intra-oral SP (50mug) induced only cheek oedema, with no deaths or excessive salivation. This oedema was prevented by pre-treating rats with SR140333, pyrilamine and pizotifen. CONCLUSION: It is likely that the deaths were due to excessive salivation induced by the particular combination of ketamine and SP. Our results are presented as a warning to other experimenters who might use these two otherwise non-toxic conditions and the consequent unexpected and needless loss of experimental animals120910, field[33]: Not in File >B?yEFreeman, P.R. Goodin, A. Troske, S. Strahl, A. Fallin, A. Green, T.C.2017mPharmacists' role in opioid overdose: Kentucky pharmacists' willingness to participate in naloxone dispensing2Journal of the American Pharmaceutical Association-online early: doi: 10.1016/j.japh.2016.12.064not published, 16 Feb 17As dispensing EDUCATION impact men NALOXONE OPIOID Opioid overdose Opioids outcome OVERDOSE PATIENT PROTOCOL RESPONSE RATE RISK SCALE SURVEY Time WHO WOMEN 1/28/2017+OBJECTIVES: To assess pharmacists' willingness to initiate the dispensing of naloxone. As of 2015, Kentucky law permits certified pharmacists to dispense naloxone under a physician-approved protocol. DESIGN: Electronic survey (e-mail) gauging perception of pharmacists' role in opioid overdose and attitudes toward, and barriers to, naloxone dispensing. SETTING AND PARTICIPANTS: All Kentucky pharmacists with active licenses in 2015. MAIN OUTCOME MEASURES: Ordinal logistic regression was used to estimate the impact of pharmacist characteristics and attitudes on willingness to initiate naloxone dispensing, where the dependent variable was operationalized as a Likert-type question on a scale of 1 (not at all willing) to 6 (very willing). RESULTS: Of 4699 practicing Kentucky pharmacists, 1282 responded, of which 834 were community practitioners (response rate 27.3%). Pharmacists reported varying willingness to initiate naloxone dispensing, with 37.3% very willing (score 5 or 6) and 27.9% not willing (score 1 or 2). However, a majority of pharmacists reported willingness to dispense naloxone with a valid prescription (54.0%, score 5 or 6). Women pharmacists were 1.3 times more likely than men to be willing to initiate naloxone dispensing (95% confidence interval [CI] 1.0-1.6). Those who reported confidence in identifying individuals at risk for overdose were 1.2 times more likely to initiate dispensing, and those who reported confidence in ability to educate patients about overdose were 1.6 times more likely to express willingness to initiate naloxone dispensing (95% CIs, respectively, 1.0-1.3 and 1.4-1.8). Community pharmacists reported barriers to naloxone access at higher rates than pharmacists from other practice settings. CONCLUSION: Kentucky pharmacists are divided in their willingness to initiate naloxone dispensing; however, those who are confident in their ability to identify overdose risks are more willing. Increasing pharmacist confidence through appropriately designed education programs could facilitate pharmacist participation in naloxone dispensing120721, field[33]: Not in File B?zFriedmann, P.D. Wilson, D. Nunes, E.V. Hoskinson, R., Jr. Lee, J.D. Gordon, M. Murphy, S.M. Bonnie, R.J. Chen, D.T. Boney, T.Y. O'Brien, C.P.2017oDo patient characteristics moderate the effect of extended-release naltrexone (XR-NTX) for opioid use disorder?$Journal of Substance Abuse Treatmentonline early: doi:not published, 01 Mar 17ABUSE ADDICTION Age ALCOHOL Alcohol use As baseline DEPRESSION DRUG DRUG ABUSE effectiveness EMPLOYMENT ENVIRONMENTAL FOLLOW UP Follow-up Gender HEALTH history INTERACTION INTOXICATION LEGAL lifestyle MANAGEMENT Mental health method methods NALTREXONE OPIOID opioid use disorder Opioids PATIENT Population PSYCHIATRIC quality Quality of life Release RISK STATUS Substance use suicidal THERAPY TREATMENT TRIAL use WHO 2/21/2017BACKGROUND: Extended release naltrexone (XR-NTX) injected intramuscularly monthly has been shown to reduce relapse in persons with opioid use disorder. Baseline factors, including patients' demographics, comorbidities and lifestyle, may help identify patients who will benefit most or least from XR-NTX treatment. METHODS: Potential moderators of XR-NTX's effect were examined in the largest North American randomized open-label effectiveness trial of XR-NTX. Relapse status (Yes/No) at 6-month follow-up was regressed on treatment group (XR-NTX, N=153; or Treatment-as-Usual [TAU], N=155), baseline covariates, and their two-way interaction to identify moderator effects. Baseline covariates included age, gender, summary scores for depression, suicidal thoughts, drug abuse risk, substance use, medical, psychiatric and employment status, socialization, legal and family/social issues, history of abuse and quality of life measures. RESULTS: Alcohol use to intoxication in the 30days before randomization was a significant moderator: during the treatment phase, those who reported being recently intoxicated before randomization to XR-NTX relapsed to opioids at a rate (56%) similar to TAU (58%), while those without alcohol intoxication in the prior 30days had a lower rate of opioid relapse (41% vs. 65%, respectively, P<0.04). CONCLUSIONS: XR-NTX appeared to work equally well across subgroups with diverse demographic, addiction, mental health and environmental characteristics, with the possible exception of working better among those without recent alcohol intoxication. These findings should be reassuring to practitioners increasingly using XR-NTX as medical addiction therapy in diverse and often vulnerable populations121062, field[33]: Not in File B?{KFu, J. Xia, X. Liu, Z. Wang, Y. Wang, Y. Shi, Q. Song, X. Song, E. Song, Y.2017The acute exposure of tetrachloro-p-benzoquinone (a.k.a. chloranil) triggers inflammation and neurological dysfunction via Toll-like receptor 4 signaling: the protective role of melatonin preconditioning Toxicology,online early: doi: 10.1016/j.tox.2017.02.015not published, 01 Mar 17ACUTE agent Anti-inflammatory ANTIOXIDANT As BRAIN CELL cytokine deficiency Differentiation ERK EXPOSURE IN VITRO IN VIVO INFLAMMATION IS knockout mice Knowledge LEVELS MELATONIN MICE MODEL NEUROLOGICAL NEUROTOXICITY Pathway PHEOCHROMOCYTOMA PROTEIN RAT Release STUDY THERAPEUTIC Time 2/23/2017JThis study is aimed to investigate the inflammation and neurological dysfunction induced by tetrachloro-p-benzoquinone (TCBQ) through Toll-like receptor 4 (TLR4) signaling. We also investigated the protective role of melatonin as an antioxidant and anti-inflammatory agent. In vitro model was established by rat pheochromocytoma PC12 cells, meanwhile, TLR4 wild-type (C57BL/6) and knockout mice (C57BL/10ScNJ TLR4-/-) were used as in vivo model. In vitro study showed TCBQ exposure enhanced the expression of TLR4, myeloid differentiation factor 88 (MyD88) at both transcriptional and post-transcriptional levels. By contrast, melatonin decreased TLR4 and MyD88 expressions. Moreover, our result indicated that melatonin disrupted the formation of TLR4/MyD88/MD2/CD14 complex. In addition, melatonin terminated TCBQ-mediated phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular regulated protein kinase (ERK) signaling and hampered its downstream pro-inflammatory cytokine releases. In vivo result also indicated TLR4 deficiency partially protected against TCBQ-induced morphological and neuropathological changes in mice brain, suggested the role of TLR4. In conclusion, melatonin modulates TCBQ-mediated inflammatory genes through TLR4/MyD88-dependent signaling pathway. Our current study, to the best of our knowledge, is the first time show melatonin not only disrupt the binding of TLR4 and MyD88, but also restricted the formation of TLR4/MD2/CD14 complex, suggesting that melatonin supplementary may represent a valuable therapeutic strategy for inflammatory neurological dysfunction121129+ field[33]: Not in FileXB?|=Fuchs, J. Casado Diaz, J.I. Jud Schefer, R. Rauber-Lüthy, C.2017Expired antivenom: good efficacy in a severely envenomed cat bitten by Sistrurus miliarius miliarius (Carolina Pigmy Rattlesnake)Clinical Toxicology0online early: doi: 10.1080/15563650.2017.1294694not published, 03 Mar 17ANTIVENOM As case CAT COAGULOPATHY EFFICACY FAILURE IN VITRO IN VIVO IS Knowledge LETTER NECROSIS RATTLESNAKE RENAL RENAL FAILURE snake bite VIPER3/1/2017121158/ field[33]: Not in File B?}8Gao, B. Chi, L. Mahbub, R. Bian, X. Tu, P. Ru, H. Lu, K.2017rMulti-omics reveals that lead exposure disturbs gut microbiome development, key metabolites and metabolic pathwaysChemical Research in Toxicology1online early: doi: 10.1021/acs.chemrestox.6b00401not published, 01 Mar 17ACID Affect As BILE Development EXPOSURE FOOD GA GAS gas chromatography mass spectrometry Gas chromatography-mass spectrometry GC-MS GUT HEALTH Homeostasis HUMAN Human health IMMUNE SYSTEM impact IS LEAD Lead exposure MECHANISM METABOLISM METABOLITE Metabolites metabolomics MICE Microbiome NITROGEN Organs OXIDATIVE STRESS Pathway PUBLIC PUBLIC HEALTH SPECTROMETRY STRESS STUDY Toxicities TOXICITY vitamin VITAMIN E WATER 2/24/2017Lead exposure remains as a global public health issue and recent Flint water crisis has again raised concern about lead toxicity in the public. The toxicity of lead has been well established in a variety of systems and organs. It has been increasingly appreciated that gut microbiome is highly involved in many critical physiological processes, such as food digestion, immune system development, and metabolic homeostasis, etc. However, despite the key role of gut microbiome in human health, the functional impact of lead exposure on gut microbiome has not been studied yet. This study aims at defining gut microbiome toxicity induced by lead exposure in C57BL/6 mice by multi-omics approaches including 16S rRNA sequencing, whole genome metagenomics sequencing and gas chromatography-mass spectrometry (GC-MS) metabolomics profiling. 16S rRNA sequencing revealed that lead exposure altered the gut microbiome trajectory and phylogenetic diversity. Metagenomics sequencing and metabolomics profiling showed that numerous metabolic pathways, including vitamin E and bile acids, nitrogen metabolism, energy metabolism, oxidative stress and defense/detoxification mechanism, were significantly disturbed by lead exposure. These perturbed molecules and pathways may have important implications in lead toxicity in the host. Taken together, we have demonstrated that lead exposure not only alters the gut microbiome community structures/diversity, but also largely affects its metabolic functions, leading to gut microbiome toxicity1209620 field[33]: Not in File7B?~3Gao, M. Igata, H. Takeuchi, A. Sato, K. Ikegaya, Y.2017cMachine learning-based prediction of adverse drug effects: an example of seizure-inducing compounds#Journal of Pharmacological Sciences-online early: doi: 10.1016/j.jphs.2017.01.003not published, 01 Mar 17ACUTE Adverse As ASSESSMENT biological CLINICAL CONCENTRATIONS Development DIPHENHYDRAMINE dose DRUG drug development drug effects drugs EXPERIMENTAL IN VITRO IS mouse PREDICTION SAFETY safety assessment seizure SEIZURES Side effect side effects side-effects STRYCHNINE THEOPHYLLINE 1/28/2017Various biological factors have been implicated in convulsive seizures, involving side effects of drugs. For the preclinical safety assessment of drug development, it is difficult to predict seizure-inducing side effects. Here, we introduced a machine learning-based in vitro system designed to detect seizure-inducing side effects. We recorded local field potentials from the CA1 alveus in acute mouse neocortico-hippocampal slices, while 14 drugs were bath-perfused at 5 different concentrations each. For each experimental condition, we collected seizure-like neuronal activity and merged their waveforms as one graphic image, which was further converted into a feature vector using Caffe, an open framework for deep learning. In the space of the first two principal components, the support vector machine completely separated the vectors (i.e., doses of individual drugs) that induced seizure-like events and identified diphenhydramine, enoxacin, strychnine and theophylline as "seizure-inducing" drugs, which indeed were reported to induce seizures in clinical situations. Thus, this artificial intelligence-based classification may provide a new platform to detect the seizure-inducing side effects of preclinical drugs121059, field[33]: Not in File ^B?JmGarcía González, E. Trenchs Sainz de la Maza, V. Martínez Sánchez, L. Ferrer Bosch, N. Luaces Cubells, C.2017<[Repeated poisoning episodes: alarm sign of risk situations]Anales de Pediatria/online early: doi: 10.1016/j.anpedi.2016.12.006not published, 01 Mar 17Age As case DETECTION Emergencies emergency FOLLOW UP Follow-up history injuries Injury IS method methods PAEDIATRIC PATIENT POISONING poisonings PREVENTION preventive measures Recurrence Retrospective study RISK STUDY 2/18/2017xINTRODUCTION: Prevention is an essential aspect in paediatric poisonings, especially when recurrent episodes are detected. The aims of this article are to detect the recurrence rate for suspected poisoning in emergency consultations, as well as to identify the cases in which specific preventive measures are indicated, and to determine whether the creation of a specific item for recurrent episodes in the computerised medical records system facilitates its detection. MATERIAL AND METHODS: A retrospective study was conducted on patients less than 18 years of age treated in the emergency room due to suspected poisoning during 2013 and 2014. Patients were divided according to the presence or absence of previous episodes. From January 2014, a specific item is present in the computerised medical records of the poisoned patient, where the history of previous episodes is registered. The preventive measures used between both groups were compared. RESULTS: A total of 731 consultations were recorded for suspected poisoning. A history of previous episodes was detected in 9% of cases. Medical injury reports and follow-up in outpatient clinics were more often performed in patients with recurrent episodes than in patients without them (28.8% vs 18.0%, P=.034, and 65.2% vs. 18.8%, P<.001, respectively). In 2013, the recurrence rate was 5.9% vs 12% in 2014 (P=.004). CONCLUSIONS: The recurrence rate observed is significant. Although preventive measures are more frequently indicated in these patients, their application is low. The creation of a specific item for recurrent episodes in a computerised medical records system facilitates their detection120940: field[22]: In Spanish with English abstract Not in File dB?Gasthuys, E. Schauvliege, S. van, Bergen T. Millecam, J. Cerasoli, I. Martens, A. Gasthuys, F. Vandecasteele, T. Cornillie, P. Van den Broeck, W. Boyen, F. Croubels, S. Devreese, M.2017Repetitive urine and blood sampling in neonatal and weaned piglets for pharmacokinetic and pharmacodynamic modelling in drug discovery: a pilot studyLaboratory animals+online early: doi: 10.1177/0023677217692372not published, 28 Feb 17Age Anaesthesia analysis ANIMAL animal models As BLOOD complications DRUG Drug discovery drugs KINETICS MALE method MODEL NEONATAL NO PAEDIATRIC PHARMACODYNAMICS pharmacokinetic PHARMACOKINETICS Population recovery STUDY SURGERY TECHNIQUE TEST URINE use Volume1/1/2017xPiglets are considered to be suitable animal models for predicting the pharmacokinetics and pharmacodynamics (PK/PD) of test drugs for potential use in the paediatric population. Such PK/PD studies require multiple blood and urine samplings. The goal of the present study was to determine a suitable blood collection strategy applicable in the youngest age categories of six days, four weeks and eight weeks of age, as well as a urine collection technique for male piglets in the same age categories. Blood was collected either by a surgically-placed jugular vein catheter (six days old [ n = 4] and four weeks old [ n = 2] piglets) or by direct venepuncture of the jugular vein (four weeks old [ n = 2] and eight weeks old [ n = 4] piglets). A non-invasive method for total volume urine collection in male piglets was also developed using a urine pouch. No specific complications were encountered during anaesthesia or surgery for jugular catheter placement. After a 24 h recovery period, urine and blood were easily collected without technical complications. One piglet was humanely killed at week 2 because of septicaemia. Histological analysis of both veins in all four piglets revealed negligible damage to the blood vessel wall. In conclusion, the presented techniques for blood (jugular catheter and direct venepuncture) and urine collection (pouches) are suitable for PK/PD studies in piglets120905* field[33]: Not in FileB?Geltzeiler, M. Steele, T.O.2017:Nasal septal perforation secondary to systemic bevacizumab"American Journal of Otolaryngology/online early: doi: 10.1016/j.amjoto.2017.01.018not published, 01 Mar 17ANTIBODIES Awareness bevacizumab CANCER case CLINICAL complications ENDOTHELIAL GROWTH GROWTH FACTOR IS LESIONS MONOCLONAL ANTIBODIES NASAL Observation PATIENT REVIEW SYMPTOMS SYSTEMIC THERAPY TOPICAL Toxicities TOXICITY TREATMENT VASCULAR WHO 1/19/2017IMPORTANCE: A case of nasal septal perforation secondary to systemic bevacizumab therapy for ovarian cancer is reported. Bevacizumab is a vascular endothelial growth factor A (VEGF-A) inhibitor that is becoming more widely utilized in the oncologic community. There is only one prior report of septal perforation secondary to bevacizumab in the Otolaryngology specific literature. The purpose of this report is: 1) to raise awareness and discuss the literature surrounding the sinonasal complications of bevacizumab and 2) provide workup and treatment recommendations based on the sum of the available literature. OBSERVATIONS: We review the clinical record of a 59year old patient who presented with an anterior septal perforation while taking bevacizumab therapy for ovarian cancer. She had mild symptoms. Her oncologist held bevacizumab and topical moisture therapy was started. After several weeks, the perforation remained stable and bevacizumab was restarted for her ovarian cancer. CONCLUSION AND RELEVANCE: Bevacizumab is associated with both septal perforation and more widespread sinonasal toxicity. These lesions tend to produce only mild symptoms and can usually be managed conservatively. The decision to hold bevacizumab therapy should be made in conjunction with the patient and medical oncologist. Otolaryngologists should be aware of the toxicity from this increasingly common oncologic therapy120938. field[33]: Not in File ?ZGendreau, K.L. Haney, R.A. Schwager, E.E. Wierschin, T. Stanke, M. Richards, S. Garb, J.E.2017House spider genome uncovers evolutionary shifts in the diversity and expression of black widow venom proteins associated with extreme toxicity178 BMC Genomics181BACTERIA BLACK WIDOW SPIDER DATA DISTRIBUTION evidence evolution family HORMONE ION TRANSPORT IS neurotoxic pain Potency PROTEIN proteins Sex SPIDER STUDY TISSUE Toxicities TOXICITY toxin TOXINS TRANSPORT Venom 2/16/2017BACKGROUND: Black widow spiders are infamous for their neurotoxic venom, which can cause extreme and long-lasting pain. This unusual venom is dominated by latrotoxins and latrodectins, two protein families virtually unknown outside of the black widow genus Latrodectus, that are difficult to study given the paucity of spider genomes. Using tissue-, sex- and stage-specific expression data, we analyzed the recently sequenced genome of the house spider (Parasteatoda tepidariorum), a close relative of black widows, to investigate latrotoxin and latrodectin diversity, expression and evolution. RESULTS: We discovered at least 47 latrotoxin genes in the house spider genome, many of which are tandem-arrayed. Latrotoxins vary extensively in predicted structural domains and expression, implying their significant functional diversification. Phylogenetic analyses show latrotoxins have substantially duplicated after the Latrodectus/Parasteatoda split and that they are also related to proteins found in endosymbiotic bacteria. Latrodectin genes are less numerous than latrotoxins, but analyses show their recruitment for venom function from neuropeptide hormone genes following duplication, inversion and domain truncation. While latrodectins and other peptides are highly expressed in house spider and black widow venom glands, latrotoxins account for a far smaller percentage of house spider venom gland expression. CONCLUSIONS: The house spider genome sequence provides novel insights into the evolution of venom toxins once considered unique to black widows. Our results greatly expand the size of the latrotoxin gene family, reinforce its narrow phylogenetic distribution, and provide additional evidence for the lateral transfer of latrotoxins between spiders and bacterial endosymbionts. Moreover, we strengthen the evidence for the evolution of latrodectin venom genes from the ecdysozoan Ion Transport Peptide (ITP)/Crustacean Hyperglycemic Hormone (CHH) neuropeptide superfamily. The lower expression of latrotoxins in house spiders relative to black widows, along with the absence of a vertebrate-targeting alpha-latrotoxin gene in the house spider genome, may account for the extreme potency of black widow venom120951. field[33]: Not in FileQB?6George, A.K. Behera, J. Kelly, K.E. Zhai, Y. Tyagi, N.2017QHydrogen sulfide, endoplasmic reticulum stress and alcohol mediated neurotoxicityBrain Research Bulletin5online early: doi: 10.1016/j.brainresbull.2017.02.002not published, 01 Mar 17nABUSE ACETALDEHYDE ADULT Affect ALCOHOL Alcohol consumption Benefits BRAIN central nervous system CNS Consumption DISEASE DRUG drugs Epigenetic modification ER stress evidence EXPOSURE HOMOCYSTEINE HYDROGEN hydrogen sulfide HYDROGEN SULPHIDE IS LEVELS MECHANISM Mechanisms METABOLISM NEUROTOXICITY OXIDATIVE STRESS REVIEW STRESS THERAPEUTIC toxic Toxicities TOXICITY 2/14/2017Alcohol is one of the most socially accepted addictive drugs in modern society. Its abuse affects virtually all organ systems with the central nervous system (CNS) being particularly vulnerable to excessive alcohol exposure. Alcohol exposure also causes profound damage to both the adult and developing brain. Excessive alcohol consumption induces numerous pathophysiological stress responses, one of which is the endoplasmic reticulum (ER) stress response. Potential mechanisms that trigger the alcohol induced ER stress response are either directly or indirectly related to alcohol metabolism, which include toxic levels of acetaldehyde and homocysteine, oxidative stress and abnormal epigenetic modifications. Growing evidence suggests that H2S is the most recently recognized gasotransmitter with tremendous physiological protective functions against oxidative stress induced neurotoxicity. In this review we address the alcohol induced oxidative stress mediated ER stress and the role of H2S in its mitigation in the context of alcohol neurotoxicity. Interruption of ER stress triggers is anticipated to have therapeutic benefits for alcohol mediated diseases and disorders1209554 field[33]: Not in FileB?UGiaquinto, P.C. de Sá, M.B. Sugihara, V.S. Gonçalves, B.B. Delício, H.C. Barki, A.2017XEffects of glyphosate-based herbicide sub-lethal concentrations on fish feeding behavior6Bulletin of Environmental Contamination and Toxicology,online early: doi: 10.1007/s00128-017-2037-2not published, 28 Feb 17Adverse ADVERSE EFFECTS Affect AGRICULTURAL ANIMAL Animals As Behavior CHOLINESTERASE CONCENTRATIONS Consumption FISH FOOD formulation GLYPHOSATE Glyphosate-based herbicide GROWTH HERBICIDES Inhibition Intake KIDNEY LIVER PLANT STUDY 2/10/2017Glyphosate-based herbicides are widely used in agricultural systems. Although the target organism are particularly plant organisms, there are numerous studies showing adverse effects in aquatic animals, such as inhibition of acetyl cholinesterase, effects on kidney, liver, and gill and stressors effects. This study analyzed the effects of commercial formulation of glyphosate on feeding behavior in Pacu (Piaractus mesopotamicus). Fish were exposed to three glyphosate concentrations (0.2, 0.6, and 1.8 ppm) for 15 days. At concentrations of 0.2 and 0.6 ppm, food intake decreased on day 13 and then returned to normal on day 15. At the highest glyphosate-based herbicide concentration, 1.8 ppm, food consumption decreased dramatically and did not recover on day 15. This study showed that glyphosate-based herbicide at sub-lethal concentrations can affect feed intake in pacu and consequently inhibits its growth120861+ field[33]: Not in File?CGibson, J. Adlard, B. Olafsdottir, K. Sandanger, T.M. Odland, J.Ø.20169Levels and trends of contaminants in humans of the Arctic33804+International Journal of Circumpolar Health751As ASSESSMENT DATA DIPHENYL DIPHENYL ETHER Environment Ether ETHERS EXPOSURE hazardous HAZARDOUS WASTE HUMAN Humans IS LEVELS MONITORING POLLUTION POLYBROMINATED DIPHENYL ETHERS Population Source TRANSPORT trends1/2016*The Arctic Monitoring and Assessment Programme (AMAP) is one of the six working groups established under the Arctic Council. AMAP is tasked with monitoring the levels of contaminants present in the Arctic environment and people as well as assessing their effects on a continuous basis, and reporting these results regularly. Most of the presented data have been collected over the last 20 years and are from all eight Arctic countries. Levels of contaminants appear to be declining in some of the monitored Arctic populations, but it is not consistent across the Arctic. Most Arctic populations continue to experience elevated levels of these contaminants compared to other populations monitored globally. There are certain contaminants, such as perfluorinated compounds and polybrominated diphenyl ethers, which are still increasing in Arctic populations. These contaminants require more investigation to find out the predominant and important sources of exposure, and whether they are being transported to the Arctic through long-range transport in the environment120722( field[33]: Not in File B?JGirardi, A. Raschi, E. Galletti, S. Allegaert, K. Poluzzi, E. De Ponti, F.2017kDrug-induced renal injury in neonates: challenges in clinical practice and perspectives in drug development0Expert Opinion On Drug Metabolism and Toxicology0online early: doi: 10.1080/17425255.2017.1290081not published, 16 Feb 17ACUTE Acute kidney injury As Biomarker BIOMARKERS CLINICAL DATA DETECTION Development DRUG drug development drug-induced drugs IDENTIFICATION Imaging IMPAIRMENT injuries Injury INTENSIVE CARE intensive care unit IS KIDNEY kidney injury Knowledge limits Long term Long-term MAGNETIC RESONANCE magnetic resonance imaging MONITORING NEONATAL neonate NEONATES NEPHROTOXICITY Occurrence PAEDIATRIC Population Regulatory RENAL RENAL TOXICITY RESEARCH Sensitivity TECHNIQUE Toxicities TOXICITY UNIT UNITS 1/31/2017dINTRODUCTION: Acute kidney injury (AKI) is frequently diagnosed in the neonatal population, especially in those admitted to intensive care units, and poses several challenges for clinicians mainly because of difficulties in timely identification of renal impairment and the need to administer drugs with potential nephrotoxicity. In this context, research on biomarkers is growing for their implication in the early detection of renal damage and their higher sensitivity in monitoring renal activity, but also as an important tool for drug development. Areas covered: We described the tools currently used to detect renal damage in neonatal settings, their limits and applicability, as well as the role of drugs on renal toxicity occurrence. Subsequently, we discuss current knowledge on new biomarkers for the detection of kidney injury and drug-induced kidney injury in neonates, and the qualification programs developed by regulatory agencies for biomarkers intended as tools in drug development. Expert opinion: Some molecules are emerging as potential biomarkers for early detection of AKI: promising data has demonstrated higher sensitivity and accuracy compared with tools currently used in the clinical setting. In addition, novel techniques (e.g. high power magnetic resonance imaging) to assess long-term consequences of AKI in neonates are in early steps of development120723/ field[33]: Not in File =?1Gobeli, A. Crossley, D., II Johnson, J. Reyna, K.2017~The effects of neonicotinoid exposure on embryonic development and organ mass in northern bobwhite quail (Colinus virginianus)9-15IComparative Biochemistry and Physiology Part C: Toxicology & Pharmacology195CONCENTRATIONS Development DEVELOPMENTAL Embryo EXPOSURE Frequency GROWTH HEART IMIDACLOPRID impact INSECTICIDE Insecticides KIDNEY lethality LIVER LUNG NEONICOTINOID neonicotinoids NO RESEARCH SPECIES SURVIVAL TREATMENT use2/7/2017Since their emergence in the early 1990s, neonicotinoid use has increased exponentially to make them the world's most prevalent insecticides. Although there has been considerable research concerning the lethality of neonicotinoids, their sub-lethal and developmental effects are still being explored, especially with regards to non-mammalian species. The goal of this research was to investigate the effects of the neonicotinoid imidacloprid on the morphological and physiological development of northern bobwhite quail (Colinus virginianus). Bobwhite eggs (n=390) were injected with imidacloprid concentrations of 0 (sham), 10, 50, 100, and 150mg/kg of egg mass, which was administered at day 0 (pre-incubation), 3, 6, 9, or 12 of growth. Embryos were dissected, weighed, staged, and examined for any overt structural deformities after 19days of incubation. The mass of the embryonic heart, liver, lungs and kidneys was also recorded. The majority of treatments produced no discernible differences in embryo morphology; however, in some instances, embryos were subject to increased frequency of anatomical deformity and altered organ masses. Some impacts were more pronounced in specific dosing periods, implying that there may be critical windows of development when embryos are more susceptible to neonicotinoid exposure. This investigation suggests that imidacloprid has the potential to impact bobwhite quail embryonic development and chick survival120868, field[33]: Not in FileB?GGomez-Berrada, M.P. Ficheux, A.S. Dahmoul, Z. Roudot, A.C. Ferret, P.J.2017XExposure assessment of family cosmetic products dedicated to babies, children and adultsFood and Chemical Toxicology,online early: doi: 10.1016/j.fct.2017.02.024not published, 01 Mar 17ADULT Age Aged As ASSESSMENT CHILDREN CLINICAL Consumption COSMETIC Cosmetics DATA EXPOSURE EXPOSURE ASSESSMENT family FOAM IS method MILK PAEDIATRIC SAFETY SHAMPOO SOAP STUDY 2/16/2017Very few consumption and exposure data is available for family cosmetic products. The aim of the present study was to assess the consumption and the exposure to family cosmetic products used by babies, children and adults. 10 categories of products were studied: shampoo, shower gel, solid soap, cleansing lotion, emollient foam, emollient bath, cream, milk, balm and lip balm. Consumption data were obtained from 2994 participants (789 babies aged 0-3 years, 837 children aged 4-12 years and 1368 adults aged more than 18 years) included in 87 clinical safety studies. Exposure was performed using a probabilistic method. The implementation of consumption and exposure assessment by age has strengthened this work, as consumption and mainly exposure differences were shown. In fact, babies were always the most exposed to family products, followed by children and adults. These original data will be useful for safety assessors and safety agencies in order to protect consumers121008+ field[33]: Not in File/?^Gondim, A.P. Nogueira, R.R. Lima, J.G. Lima, R.A. Albuquerque, P.L. Veras, M.D. Ferreira, M.A.2017Suicide attempts by exposure to toxic agents registered in a Toxicological Information and Assistance Center in Fortaleza, Ceara, Brazil, 2013109-119!Epidemiologia e Servicos de Saude261agent AGRICULTURAL case DATA DEATH EPIDEMIOLOGY EXPOSURE FEMALE HOME INFORMATION Intake IS Medicine medicines method methods pesticide PESTICIDES PREVENTION STUDY SUICIDE toxic Urban use1/2017Objective:: to describe cases of suicide attempts by exposure to toxic agents registered by the Toxicological Information and Assistance Center in Fortaleza, Ceara, Brazil. Methods:: this is a descriptive study using secondary data of the cases registered in 2013. Results:: 410 cases were registered; 56.2% of the individuals were female and 79.7% were between 12 and 39 years old; most of them (86.4%) lived in urban areas and 67.2%, in Fortaleza; in 94.9% of the cases, the exposure took place in the individual's own home; the toxic agents most commonly used were pesticides (42.9%), especially for agricultural use (30.2%), medicines (39.5%) and house cleaning products (3.4%); of 16 suicide attempts that resulted in death, 15 were caused by agricultural pesticides. Conclusion:: the study shows that the intake of toxic agents, especially of agricultural pesticides, is a common method used in suicide attempts; the integration between actions of promotion and prevention are essential1209951 field[33]: Not in File|??Gooch, A. Sizochenko, N. Sviatenko, L. Gorb, L. Leszczynski, J.2017A quantum chemical based toxicity study of estimated reduction potential and hydrophobicity in series of nitroaromatic compounds133-150&SAR and QSAR in Environmental Research282ANIMAL Animals As BACTERIA CELL chemical CYTOTOXICITY DATA Environment HUMAN Humans HYDROPHOBICITY MECHANISM Mechanisms MODEL Oxidation P PROTOCOL Protocols Reduction SOFTWARE SOLVENT STUDY toxic Toxicities TOXICITY Toxicity study2/2017ONitroaromatic compounds and the products of their degradation are toxic to bacteria, cells and animals. Various studies have been carried out to better understand the mechanism of toxicity of aromatic nitrocompounds and their relationship to humans and the environment. Recent data relate cytotoxicity of nitroaromatic compounds to their single- or two-electron enzymatic reduction. However, mechanisms of animal toxicity could be more complex. This work investigates the estimated reduction and oxidation potentials of 34 nitroaromatic compounds using quantum chemical approaches. All geometries were optimized with density functional theory (DFT) using the solvation model based on density (SMD) and polarizable continuum model (PCM) solvent model protocols. Quantitative structure-activity/property (QSAR/QSPR) models were developed using descriptors obtained from quantum chemical optimizations as well as the DRAGON software program. The QSAR/QSPR equations developed consist of two to four descriptors. Correlations have been identified between electron affinity (ELUMO) and hydrophobicity (log P)121111/ field[33]: Not in File?@Goonasekera, C. Bedford, J. Harpreet, S. Giombini, M. Sheikh, A.2016uEmergency anesthesia for evacuating a traumatic acute subdural hemorrhage in a child overdosed with hypertonic saline328-330"Journal of Pediatric Neurosciences114ACUTE Adverse ADVERSE EFFECTS case CASE REPORT Case-report child dose Emergencies emergency errors FOLLOW UP Follow-up hemorrhage MANAGEMENT NO PAEDIATRIC recovery SALT SODIUM SODIUM CHLORIDE SURGERY Time Toxicities TOXICITY10/2016A previously healthy 1-year-old child with a traumatic acute subdural hemorrhage received 10 times higher dose of hypertonic saline inadvertently immediately before surgery. This case report describes deviations in fluid management needed to alleviate salt toxicity and its adverse effects during surgery under anesthesia perioperatively. The child made an uneventful recovery with no evident residual damage at follow-up121055- field[33]: Not in File ?JHGouran Ourimi, E. Shabani, A. Alavi, K. Najarzadegan, M.R. Mirfazeli, F.2016A comparison of pattern of psychiatric symptoms in inpatients with bipolar disorder type one with & without methamphetamine use421/Medical Journal of the Islamic Republic of Iran30Age AMFETAMINE ASSESSMENT bipolar CLINICAL COMPARISON duration hospitalization ILLNESS impact INTOXICATION IS MALE MANIA METHAMPHETAMINE Methamphetamine use method methods NO outbreak PATIENT PSYCHIATRIC SCALE STUDY SYMPTOMS TEST use2016Background: Iran is facing an outbreak of methamphetamine-induced disorders and frequent use of these substances in patients with bipolar disorder. Using or intoxication of methamphetamine in patients with bipolar I disorder may alter the patient's clinical profile; however there is limited studies about impact of methamphetamine on clinical manifestation of bipolar disorders. This study aimed to compare psychiatric symptoms in patients with bipolar I disorder with and without concomitant use of methamphetamine. Methods: In a cross-sectional study, psychiatric symptoms of bipolar I disorder in patients with (Meth+) and without (Meth-) methamphetamine use was evaluated. A number of 57 participants with Meth + and 50 subjects with Meth- were recruited. The clinical picture of bipolar disorder was investigated by Young Mania Rating Scale (YMRS), 17-item Hamilton Depressive Rating Scale (HDRS-17) and the Scale for Assessment of Positive Symptoms (SAPS). Statistical comparisons were performed using the T-test for independent samples and Mann- Whitney test. Results: There was no statistically significant difference between two groups regarding age, duration of illness and hospitalizations. However, male participants were significantly higher in Meth+ group than in Meth- one (p<0.001). The mean (+/- SD) scores in the two groups of Meth+ and Meth- for YMRS, HDRS, and SAPS were 31.3 (+/-1.3) and 34.0 (+/-1.2), 13.7 (+/-0.7) and 13.5+/-(0.5), and 50.0 (+/-1.9) and 48.0 (+/-2.1), respectively, which were not statistically significant (p<0.05). Conclusion: There was no significant difference in the overall clinical manifestation of bipolar I disorder in patients with and without methamphetamine use. However, in some symptomatology domains, there were some differences between the two groups1210695 Not in FileM?(Gowing, L. Ali, R. White, J.M. Mbewe, D.2017,Buprenorphine for managing opioid withdrawalCD002025'Cochrane Database of Systematic Reviews2Adverse ADVERSE EFFECTS analysis As author BUPRENORPHINE CLONIDINE COMPARISON DATA DATA COLLECTION dose dose reduction duration effectiveness evidence Incidence INFORMATION IS LOFEXIDINE MALE MEDLINE Meta-analysis METHADONE method methods NALTREXONE NO OPIOID Opioid withdrawal Opioids outcome PATIENT PLACEBO PREVENTION quality Reduction RESEARCH REVIEW RISK SEVERITY Sex Signs and symptoms STUDY SYMPTOMS Syndrome Time TREATMENT Treatment Outcome TRIAL use WHO WITHDRAWAL Withdrawal symptoms 2/21/2017BACKGROUND: Managed withdrawal is a necessary step prior to drug-free treatment or as the endpoint of substitution treatment. OBJECTIVES: To assess the effects of buprenorphine versus tapered doses of methadone, alpha2-adrenergic agonists, symptomatic medications or placebo, or different buprenorphine regimens for managing opioid withdrawal, in terms of the intensity of the withdrawal syndrome experienced, duration and completion of treatment, and adverse effects. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 11, 2016), MEDLINE (1946 to December week 1, 2016), Embase (to 22 December 2016), PsycINFO (1806 to December week 3, 2016), and the Web of Science (to 22 December 2016) and handsearched the reference lists of articles. SELECTION CRITERIA: Randomised controlled trials of interventions using buprenorphine to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent. Comparison interventions involved reducing doses of methadone, alpha2-adrenergic agonists (clonidine or lofexidine), symptomatic medications or placebo, and different buprenorphine-based regimens. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 27 studies involving 3048 participants. The main comparators were clonidine or lofexidine (14 studies). Six studies compared buprenorphine versus methadone, and seven compared different rates of buprenorphine dose reduction. We assessed 12 studies as being at high risk of bias in at least one of seven domains of methodological quality. Six of these studies compared buprenorphine with clonidine or lofexidine and two with methadone; the other four studies compared different rates of buprenorphine dose reduction.For the comparison of buprenorphine and methadone in tapered doses, meta-analysis was not possible for the outcomes of intensity of withdrawal or adverse effects. However, information reported by the individual studies was suggestive of buprenorphine and methadone having similar capacity to ameliorate opioid withdrawal, without clinically significant adverse effects. The meta-analyses that were possible support a conclusion of no difference between buprenorphine and methadone in terms of average treatment duration (mean difference (MD) 1.30 days, 95% confidence interval (CI) -8.11 to 10.72; N = 82; studies = 2; low quality) or treatment completion rates (risk ratio (RR) 1.04, 95% CI 0.91 to 1.20; N = 457; studies = 5; moderate quality).Relative to clonidine or lofexidine, buprenorphine was associated with a lower average withdrawal score (indicating less severe withdrawal) during the treatment episode, with an effect size that is considered to be small to moderate (standardised mean difference (SMD) -0.43, 95% CI -0.58 to -0.28; N = 902; studies = 7; moderate quality). Patients receiving buprenorphine stayed in treatment for longer, with an effect size that is considered to be large (SMD 0.92, 95% CI 0.57 to 1.27; N = 558; studies = 5; moderate quality) and were more likely to complete withdrawal treatment (RR 1.59, 95% CI 1.23 to 2.06; N = 1264; studies = 12; moderate quality). At the same time there was no significant difference in the incidence of adverse effects, but dropout due to adverse effects may be more likely with clonidine (RR 0.20, 95% CI 0.04 to 1.15; N = 134; studies = 3; low quality). The difference in treatment completion rates translates to a number needed to treat for an additional beneficial outcome of 4 (95% CI 3 to 6), indicating that for every four people treated with buprenorphine, we can expect that one additional person will complete treatment than with clonidine or lofexidine.For studies comparing different rates of reduction of the buprenorphine dose, meta-analysis was possible only for treatment completion, with separate analyses for inpatient and outpatient settings. The results were diverse, and we assessed the quality of evidence as being very low. It remains very uncertain what effect the rate of dose taper has on treatment outcome. AUTHORS' CONCLUSIONS: Buprenorphine is more effective than clonidine or lofexidine for managing opioid withdrawal in terms of severity of withdrawal, duration of withdrawal treatment, and the likelihood of treatment completion.Buprenorphine and methadone appear to be equally effective, but data are limited. It remains possible that the pattern of withdrawal experienced may differ and that withdrawal symptoms may resolve more quickly with buprenorphine.It is not possible to draw any conclusions from the available evidence on the relative effectiveness of different rates of tapering the buprenorphine dose. The divergent findings of studies included in this review suggest that there may be multiple factors affecting the response to the rate of dose taper. One such factor could be whether or not the initial treatment plan includes a transition to subsequent relapse prevention treatment with naltrexone. Indeed, the use of buprenorphine to support transition to naltrexone treatment is an aspect worthy of further research.Most participants in the studies included in this review were male. None of the studies reported outcomes on the basis of sex, preventing any exploration of differences related to this variable. Consideration of sex as a factor influencing response to withdrawal treatment would be relevant research for selecting the most appropriate type of intervention for each individual1209710 field[33]: Not in File ?"Grapp, M. Kaufmann, C. Ebbecke, M.2017Toxicological investigation of forensic cases related to the designer drug 3,4-methylenedioxypyrovalerone (MDPV): detection, quantification and studies on human metabolism by GC-MS1-9Forensic Science International273ZAge analysis As Benzodiazepine BENZODIAZEPINES BLOOD Blood samples CANNABINOID cannabinoids case CATHINONE Cathinones COCAINE CONCENTRATIONS Confirmation Consumption designer drug DESIGNER DRUGS DETECTION DRUG drugs EXPOSURE FORENSIC GA GAS gas chromatography mass spectrometry Gas chromatography-mass spectrometry GC-MS Germany HUMAN Humans IS Laboratories LABORATORY MDPV men METABOLISM METABOLITE Metabolites NOVEL PSYCHOACTIVE SUBSTANCES Occurrence OPIATES Pathway Psychostimulant PSYCHOTROPIC DRUGS quantification SERUM SPECTROMETRY STUDY synthetic cathinone Synthetic cathinones URINE Variability2/2/20173,4-methylenedioxypyrovalerone (MDPV) is a synthetic cathinone belonging to the class of alpha-pyrrolidinophenones that become increasingly popular as a designer psychostimulant. Here, we report a comprehensive collection of MDPV exposure with quantitative serum level confirmation in Germany. During the years 2014-2016, we could proof consumption of MDPV in 23 cases where urine and blood samples were submitted to our laboratory by the police of Lower Saxony. Most of the samples underwent systematic toxicological analysis by gas chromatography-mass spectrometry (GC-MS), where MDPV could be detected in urine and/or serum samples. The determined concentrations of MDPV in serum showed a high variability, ranging from traces (<10ng/mL) up to 576ng/mL with a mean concentration of 118ng/mL and median of 47ng/mL. The majority of MDPV users were men (87%) and the age ranged from 23 to 49 years (mean 35.9, median 37 years). For most of the analytically confirmed MDPV cases we could prove co-consumption of other psychotropic drugs with frequent occurrence of opiates and cannabinoids in 22% of the cases, followed by benzodiazepines and cocaine in 17%. Analysis of urine samples by GC-MS disclosed the presence of MDPV and its metabolites 2'-oxo-MDPV, demethylenyl-MDPV, demethylenyl-methyl-MDPV, demethylenyl-oxo-MDPV, demethylenyl-methyl-oxo-MDPV and demethylenyl-methyl-N,N-bisdealkyl-MDPV. The metabolite pattern substantiates previous suggestions for principle metabolic pathways of MDPV in humans1208821 field[33]: Not in File lB?rGreen, T.C. Case, P. Fiske, H. Baird, J. Cabral, S. Burstein, D. Schwartz, V. Potter, N. Walley, A.Y. Bratberg, J.2017Perpetuating stigma or reducing risk? Perspectives from naloxone consumers and pharmacists on pharmacy-based naloxone in 2 states/Journal of the American Pharmacists Association-online early: doi: 10.1016/j.japh.2017.01.013not published, 01 Mar 17ADDICTION analysis As Awareness CHRONIC chronic pain College COMPARISON DATA EVIDENCE-BASED HEALTH IS NALOXONE OPIOID opioid use disorder Opioids outcome pain PATIENT PUBLIC Qualitative RISK SAFETY Synthesis use WHO 2/14/2017OBJECTIVES: Little is known about attitudes of pharmacists and consumers to pharmacy naloxone. We examined perceptions and experiences of pharmacy naloxone from people with opioid use disorder, patients taking chronic opioids for pain, caregivers of opioid users, and pharmacists from 2 early pharmacy naloxone adopter states: Massachusetts and Rhode Island. DESIGN: Eight focus groups (4 per state) were held in October to December 2015. SETTING AND PARTICIPANTS: Participants were recruited from pharmacies, health clinics, and community organizations; pharmacists were recruited from professional organizations and pharmacy colleges. OUTCOME MEASURES: Focus groups were led by trained qualitative researchers using a topic guide, and recorded and transcribed for analysis. Five analysts developed and applied a coding scheme to transcripts. Thematic analysis involved synthesis of coded data and connections between key themes, with comparisons across the groups. RESULTS: Sixty-one participants included patients with chronic pain (n = 15), people with opioid use disorders (n = 19), caregivers (n = 16), and pharmacists (n = 11). A majority of pharmacists had dispensed naloxone to patients; a minority of all consumer participants had obtained pharmacy naloxone. Four themes emerged: consumer fear of future consequences if requesting naloxone; pharmacists' concerns about practice logistics related to naloxone; differing perceptions of how opioid safety is addressed in the pharmacy; and solutions to addressing these barriers. Whereas consumer groups differed in awareness of naloxone and availability at pharmacies, all groups expressed support for the pharmacist's role and preferences for a universal offer of naloxone based on clear criteria. CONCLUSION: Pharmacies complement community naloxone provision to patients and caregivers. To overcome stigma of naloxone receipt, increased public awareness of naloxone and pharmacist training about naloxone and addiction are required. Pharmacists should offer naloxone via universal opt-out strategies-where all patients meeting evidence-based criteria are offered naloxone-rather than targeted or opt-in strategies-where only patients perceived as high risk or patients who request it are offered naloxone121034, field[33]: Not in File*B?#Green, T.C. Potter, N. Bratberg, J.20175Detecting naloxone prejudices in the pharmacy setting2Journal of the American Pharmaceutical Association-online early: doi: 10.1016/j.japh.2016.12.068not published, 16 Feb 17LETTER NALOXONE 1/31/2017120724, field[33]: Not in FileB?Gullett, B.K. Aurell, J. Holder, A. Mitchell, W. Greenwell, D. Hays, M. Conmy, R. Tabor, D. Preston, W. George, I. Abrahamson, J.P. Vander Wal, R. Holder, E.2017fCharacterization of emissions and residues from simulations of the Deepwater Horizon surface oil burnsMarine Pollution Bulletin2online early: doi: 10.1016/j.marpolbul.2017.01.083not published, 01 Mar 17analysis AROMATIC HYDROCARBONS Burn BURNS Characterization chemical CHEMICAL INCIDENT DATA Emissions HYDROCARBON impact Mexico OIL PAH particulate Particulate matter PETROL Pollutant RESIDUE Residues SCALE SIMULATION Testing Toxicities TOXICITY WATER 2/20/2017The surface oil burns conducted by the U.S. Coast Guard from April to July 2010 during the Deepwater Horizon disaster in the Gulf of Mexico were simulated by small scale burns to characterize the pollutants, determine emission factors, and gather particulate matter for subsequent toxicity testing. A representative crude oil was burned in ocean-salinity seawater, and emissions were collected from the plume by means of a crane-suspended sampling platform. Emissions included particulate matter, aromatic hydrocarbons, polychlorinated dibenzodioxins/dibenzofurans, elements, and others, the sum of which accounted for over 92% by mass of the combustion products. The unburned oil mass was 29% of the original crude oil mass, significantly higher than typically reported. Analysis of alkanes, elements, and PAHs in the floating residual oil and water accounted for over 51% of the gathered mass. These emission factors, along with toxicity data, will be important toward examining impacts of future spill burning operations1210681 field[33]: Not in File (?)Gupta, V. Gupta, K. Singh, G. Kaushal, S.2016mAn analytical study to correlate serum levels of levetiracetam with clinical course in patients with epilepsy31-36*Journal of Neurosciences in Rural Practice75ACID ADR Adverse Adverse drug reaction adverse drug reactions Age ANALYTICAL Antiepileptic As CHROMATOGRAPHY CLINICAL DATABASE DOSAGE dose DRUG drugs EFFICACY ENZYME EPILEPSY ETHICS Frequency Gender high performance liquid chromatography India INDIUM IS LEVELS LEVETIRACETAM Liquid chromatography method methods MONITORING NO PATIENT Population PRESCRIBING r REACTIONS seizure SERUM STUDY THERAPEUTIC Therapeutic drug monitoring Time tolerability Toxicities TOXICITY use VALPROIC ACID12/2016INTRODUCTION: With the advancement of therapeutics, newer antiepileptic drugs (AEDs) like Levetiracetam (LEV), with good therapeutic efficacy and tolerability are available. But unfortunately, therapeutic drug monitoring is not routinely done in India for these drugs. OBJECTIVES: The objective of this study is to determine the range of serum levels of LEV in patients at stabilized doses and correlate them with their clinical course. MATERIALS AND METHODS: Patients with epilepsy and started on LEV were enrolled from the Neurology Department after the Ethics Committee approval. Serum levels of LEV were estimated using high-performance liquid chromatography and correlated with patient demographics, dosage, dosage forms, concomitant AEDs, compliance of the patient, therapeutic effect, adverse drug reactions (ADRs), and suspected toxicity. RESULTS: Serum levels of LEV ranged from 0.4 to 102.2 mug/ml at different time points and demonstrated a negligible positive correlation with age of the patients (r = 0.12) but negligible negative correlation with bodyweight (r = -0.19). No conclusive relationship could be established for dose, gender, dosage forms, clinical efficacy (seizure frequency), ADRs, and toxicity. Compliance was verified in all the patients. Levels were found to reduce with the use of concomitant enzyme inducer drugs (56.78%) whereas increase with valproic acid (7.8%). CONCLUSION: These findings emphasize the need for monitoring the serum levels of newer AEDs like LEV considering the various parameters studied here, so as to maintain the therapeutic efficacy by preventing under or over dosage and to generate a broader database of serum levels of LEV in the Indian population to help appropriate prescribing with more confidence120902* field[33]: year=2016 volume=7 issue=5 spage=31 epage=36 aulast=Gupta Not in File 0?VGutiérrez-Rebolledo, G.A. Pérez-González, M.Z. Zamilpa, A. Jiménez-Arellanes, M.A.2017iAnti-inflammatory evaluation and acute toxicity of three food supplements that contain Moussonia deppeana141-147*Asian Pacific Journal of Tropical Medicine102mACID ACUTE Acute toxicity Anti-inflammatory Body Weight CHROMATOGRAPHY DIETARY Dietary supplement Dietary supplements dose EAR edema EVALUATION EXPERIMENTAL FOOD FOOD SUPPLEMENTS formulation HERBAL MEDICINE high performance liquid chromatography Inhibition lethal Liquid chromatography Medicine medicines method methods MICE MODEL TABLETS Toxicities TOXICITY WEIGHT2/2017yOBJECTIVE: To identify the anti-inflammatory activity through two murine models and in the median Lethal Dose (LD50) of three dietary supplements that contain Moussonia deppeana. METHODS: The anti-inflammatory activity of three dietary supplements (Cicatrisan/Gastricus(R), Gastinol(R), and Gastrovita(R)) EtOH extracts was evaluated by TPA and by carrageenan murine models; also, median Lethal Dose (LD50) was determined. Verbascoside was quantified by High-Performance Liquid Chromatography. beta-sitosterol, stigmasterol and the mixture of ursolic and oleanolic acids were identified in all supplements by TLC; however, none of these dietary supplements contain verbascoside. RESULTS: For the TPA model, Cicatrisan/Gastricus(R) generated a notable effect with 38.24% inhibition. While in the carrageenan model, it also exhibited noteworthy anti-inflammatory activity of ear edema with 66.39% of paw edema inhibition at 150 mg/kg, followed by Gastinol(R) and Gastrovita(R) with approximately 50% at 300 mg/kg. Finally, LD50 was >2 g/kg for all supplements, when was administered intragastrically and Body Weight (BW) gain in mice was not altered after 14 days. CONCLUSIONS: Of the three food supplements containing M. deppeana, only the EtOH extract from Cicatrisan/Gastricus(R) formulation (tablets) showed significant anti-inflammatory activity in both experimental models and the LD50 was >2 g/kg120947- field[33]: Not in FileH?Habib, S. Shaikh, O.S.2017 Drug-induced acute liver failure151-162Clinics in Liver Disease211ACUTE acute liver failure Affect Antiepileptic ANTIEPILEPTICS ANTIMICROBIAL antimicrobials CEREBRAL COAGULOPATHY complications drug induced liver injury drug-induced Drug-induced liver injury edema FAILURE HEPATOTOXICITY HYPERTENSION injuries Injury INTENSIVE CARE IS LIVER Liver failure liver injury Liver Transplantation MORTALITY outcome PATIENT recovery RENAL RESPIRATORY STATIN TRANSPLANT WOMEN2017Drug-induced acute liver failure (ALF) disproportionately affects women and nonwhites. It is most frequently caused by antimicrobials and to a lesser extent by complementary and alternative medications, antiepileptics, antimetabolites, nonsteroidals, and statins. Most drug-induced liver injury ALF patients have hepatocellular injury pattern. Cerebral edema and intracranial hypertension are the most serious complications of ALF. Other complications include coagulopathy, sepsis, metabolic derangements, and renal, circulatory, and respiratory dysfunction. Although advances in intensive care have improved outcome, ALF has significant mortality without liver transplantation. Liver-assist devices may provide a bridge to transplant or to spontaneous recovery. Copyright © 2016120823+ field[33]: Not in File %B?4Haboush-Deloye, A. Marquez, E.R. Gerstenberger, S.L.2017LDetermining childhood blood lead level screening compliance among physiciansJ Community Health,online early: doi: 10.1007/s10900-017-0317-8not published, 01 Mar 17adherence Age As BLOOD Blood lead childhood CHILDREN COST DATA DISEASE Guidelines INSURANCE LEAD Lead Poisoning LEVELS NON-COMPLIANCE PAEDIATRIC POISONING PREVENTION RISK SCREENING STUDY Testing WHO 2/16/20178Childhood Lead Poisoning Prevention Programs throughout the U.S. have addressed childhood lead poisoning by implementing primary and secondary prevention efforts. While many programs have helped increase screening rates, in some states children under the age of six still have not been tested for lead. This study aims to identify the barriers to childhood blood lead testing and develop a strategy to increase the number of children tested. Clark County physicians who work with children six and under were surveyed about blood lead level (BLL) testing practices, particularly, adherence to Centers for Disease Control and Prevention (CDC) guidelines, and parental compliance with orders to have their children tested to determine their blood lead levels. In addition, select in-person interviews were conducted with physicians who reported high parental compliance to identify best practices and barriers. Of the 77 physicians that provided data, 48% indicated they did not follow CDC guideline compared to 52% who follow guidelines. 18 of the 30 (or 60%) physicians reported more than 80% of parents complied with doctor recommended BLL testing. Twelve physicians identified cost, lack of insurance, and absence of symptomology as persistent barriers to lead screening. This study identified barriers to childhood lead screening including inadequate parental adherence to physician-ordered screenings and physician non-compliance with screening recommendations are two primary contributors. Addressing these issues could increase screening in children and reduce the risk of lead poisoning121043, field[33]: Not in File \?MHahn, R.Z. Antunes, M.V. Costa, A.P. Andriguetti, N.B. Verza, S.G. Linden, R.2017Determination of topiramate in dried blood spots using single-quadrupole gas chromatography-mass spectrometry after flash methylation with trimethylanilinium hydroxide131-137Journal of Chromatography B1046wADULT ANALYTICAL ASSAY BLOOD blood concentration CAPILLARY CELL CLINICAL CONCENTRATIONS determination dose DRUG ERYTHROCYTE EXTRACTION GA GAS gas chromatography mass spectrometry Gas chromatography-mass spectrometry GC-MS Intake IS Measurement method MONITORING ORAL PATIENT PLASMA quantification SPECTROMETRY STUDY THERAPEUTIC Therapeutic drug monitoring Time TOPIRAMATE use2/1/2017sDried blood spots (DBS) sampling obtained from fingerpricks is a promising and patient friendly alternative for obtaining samples for drug quantification, that could be of interest for topiramate (TOP) therapeutic drug monitoring. The aim of this study was to develop and validate a simple and fast GC-MS assay for TOP measurement in dried blood spots (DBS). The method uses a liquid extraction of one 8mm DBS, followed by a flash methylation with TMAH, and separation in a DB-5ms capillary column. Total analytical run time was 15min. Precision assays presented CV% lower than 9.1% and accuracy was in the range of 94.5-115%. TOP was stable at 25 and 45 degrees C up to 21days. TOP presents saturable binding to red blood cells, resulting in a fraction in plasma (fp) of 0.09-0.03 at 0.8mugml-1 and 0.71-0.45 at 20mugml-1 (both at 25-50 Hct% range). The method was applied to DBS samples obtained after phlebotomy and fingerpicks from an adult individual after oral intake of 100mg TOP (0.25-96h post dose). Plasma and DBS concentrations were moderately correlated (r=0.61), with estimated fp values in the range of 0.06-0.18. Translation of TOP DBS to plasma concentrations is challenging due to its concentration-dependent binding to erythrocytes. Thus, the use of whole blood concentrations for patients monitoring should be considered, which favors to the use of DBS in the clinical context120896/ field[33]: Not in FileB?:Hammer, B. Wu, Y. Fischer, S. Liu, W. Weil, T. Müllen, K.2017bControlling cellular uptake and toxicity of polyphenylene dendrimers by chemical functionalization ChemBioChem)online early: doi: 10.1002/cbic.201700079not published, 01 Mar 17fBehavior biological CELL CELLULAR UPTAKE chemical DRIVING IS NO PLASTICS Synthesis Toxicities TOXICITY 2/21/2017qPolyphenylene dendrimers (PPDs) represent a unique class of macromolecules based on their monodisperse and shape-persistent nature. These characteristics have enabled the synthesis of a new genre of "patched" surface dendrimers where their exterior can be functionalized with a variety of polar and unpolar substituents to yield lipophilic binding sites in a site-specific way. While such materials have proven capable of complexing biologically relevant molecules, shown high cellular uptake in various cell lines, and low to no toxicity; there is minimal understanding of the driving forces to these characteristics. Therefore, the present work aims at investigating whether it is the specific chemical functionalities, relative quantities of each moiety, or the "patched" surface patterning on the dendrimers that more significantly influences their behavior in biological media120963( field[33]: Not in FileB?'Hand, D.J. Short, V.L. Abatemarco, D.J.2017Substance use, treatment, and demographic characteristics of pregnant women entering treatment for opioid use disorder differ by United States census region$Journal of Substance Abuse Treatment-online early: doi: 10.1016/j.jsat.2017.01.011not published, 16 Feb 17ABUSE As Benzodiazepine BENZODIAZEPINES case DRUG drugs EDUCATION HEROIN INSURANCE IS medication assisted treatment OPIOID opioid use disorder Opioids policy School SUBSTANCE ABUSE Substance use TEST Time TREATMENT UNITED STATES use WOMEN2/1/2017eOpioid use disorder (OUD) among pregnant women increased substantially between 1992 and 2012 across the United States, with the greatest increases occurring in the southern states. We analyzed the 2013 Treatment Episodes Database-Admissions to determine how substances used, characteristics of treatment, and demographics of pregnant women entering treatment for opioid use disorder vary between geographical regions. Analyses were restricted to cases where women reported being pregnant at the time of admission and reported opioids as the primary substance problem leading to the treatment admission. Characteristics were compared between U.S. census regions using Chi-square tests and logistic regression with the South census region as the reference group. Compared to the South, pregnant women admitted for OUD treatment in other regions were 33-79% less likely to use benzodiazepines, twice as likely to be admitted to medication assisted treatment (MAT), 2-3 times more likely to use heroin, and up to 1.5 times more likely to inject drugs. Fewer women in the South reported having medical insurance, education beyond high school, and being married. There is a need in the southern U.S. for policies and treatment programs to target reducing concomitant opioid and benzodiazepine use, increasing access to, and utilization of, MAT, and increasing access to medical insurance120725, field[33]: Not in File ?jHanda, T. Hirai, T. Izumi, N. Eto, S.I. Tsunoda, S.I. Nagano, K. Higashisaka, K. Yoshioka, Y. Tsutsumi, Y.2017Identifying a size-specific hazard of silica nanoparticles after intravenous administration and its relationship to the other hazards that have negative correlations with the particle size in mice135101Nanotechnology2813ACUTE Acute toxicity Benefits biological CELL HAZARD HISTAMINE HYPOTHERMIA INTRAVENOUS IS lethal LIVER MICE NANOPARTICLES NEUTROPHILS SEVERITY SILICA STUDY THROMBOCYTOPENIA toxic Toxicities TOXICITY 2/27/2017DMany of the beneficial and toxic biological effects of nanoparticles have been shown to have a negative correlation with particle size. However, few studies have demonstrated biological effects that only occur at specific nanoparticle sizes. Further elucidation of the size-specific biological effects of nanoparticles may reveal not only unknown toxicities, but also novel benefits of nanoparticles. We used surface-unmodified silica particles with a wide range of diameters and narrow size intervals between the diameters (10, 30, 50, 70, 100, 300, and 1000 nm) to investigate the relationship between particle size and acute toxicity after intravenous administration in mice. Negative correlations between particle size and thrombocytopenia, liver damage, and lethal toxicity were observed. However, a specific size-effect was observed for the severity of hypothermia, where silica nanoparticles with a diameter of 50 nm induced the most severe hypothermia. Further investigation revealed that this hypothermia was mediated not by histamine, but by platelet-activating factor, and it was independent of the thrombocytopenia and the liver damage. In addition, macrophages/Kupffer cells and platelets, but not neutrophils, play a critical role in the hypothermia. The present results reveal that silica nanoparticles have particle size-specific toxicity in mice, suggesting that other types of nanoparticles may also have biological effects that only manifest at specific particle sizes. Further study of the size-specific effects of nanoparticles is essential for safer and more effective nanomedicines121075( field[33]: Not in FileB?HHarchegani, A.L. Hemmati, A.A. Nili-Ahmadabadi, A. Darabi, B. Shabib, S.2017bCromolyn sodium attenuates paraquat-induced lung injury by modulation of proinflammatory cytokines Drug Research(online early: doi: 10.1055/s-0042-123711not published, 01 Mar 17ANIMAL Animals As cytokine CYTOKINES dose HISTOLOGY injuries Injury LEVELS LUNG lung injury lung tissue ORAL PARAQUAT RAT rats SERUM SODIUM STUDY TISSUE TREATMENT Vehicle 2/21/2017-The current study aimed to investigate the effects of Cromolyn Sodium (CS) on proinflammatory cytokines in Paraquat (PQ)-induced lung damage in rat. Animals were randomly divided into 5 groups. Group 1 and 2 received nebulized vehicle and CS (8 mg/kg) for 3 consecutive weeks, respectively. Group 3 was treated with single oral dose of PQ (40 mg/kg). Groups 4 and 5 were PQ groups which received nebulized CS (6 and 8 mg/kg/day, respectively) from 1 week before to 2 weeks after PQ administration. Finally, the animals were scarified and the changes of hydroxyproline (HP) and histology were evaluated in lung tissue. In addition, IL-1beta, TNF-alpha and IL-8 levels were determined in serum samples. The results showed that lung HP level as well as IL-1beta, TNF-alpha and IL-8 were significantly lower in the CS treated rats as compared to PQ group. The best response, however, was observed with the 8 mg/kg of CS as confirmed by histology findings. This study suggests that CS may prevent progression of PQ-induced lung damage by decreasing of inflammatory cytokines120979' field[33]: Not in File B?:Hatten, B.W. French, L.K. Horowitz, B.Z. Hendrickson, R.G.20175Outcomes after high-concentration peroxide ingestionsAnnals of Emergency Medicine4online early: doi: 10.1016/j.annemergmed.2016.11.022#not published, 16 Feb 17, 17 Mar 17analysis As CARDIAC case Cohort DATA DATABASE DEATH DIAGNOSIS ECG EMBOLISM ENDOSCOPY evidence EXPOSURE HYPERBARIC OXYGEN hyperbaric oxygen therapy HYPOXIA Incidence INGESTION IS LESIONS MENTAL STATUS MET method methods MODEL outcome OXYGEN PATIENT Peroxide Poison poison centers PULMONARY pulmonary embolism RESPIRATORY respiratory distress REVIEW seizure STATISTICS STATUS STUDY SYMPTOMS THERAPY US use 1/19/2017STUDY OBJECTIVE: In cases of high-concentration peroxide ingestion reported to US poison centers, we describe medical outcomes, examine the role of hyperbaric oxygen, and review the use of endoscopy. METHODS: The study was a retrospective analysis of a structured database, the National Poison Data System. The chart for each poison center case of a high-concentration (>10%) peroxide ingestion was obtained and abstracted in a standardized fashion; 1,054 cases were initially considered and 294 cases met inclusion criteria. The primary outcome of possible embolic event was defined as seizure, altered mental status, respiratory distress, hypoxia, hemodynamic instability, ECG changes, radiographic evidence of cerebrovascular accident, focal neurologic deficit on examination, pulmonary embolism, cardiac emboli, elevated troponin level, physician bedside diagnosis, or rapid improvement after hyperbaric oxygen therapy. Both descriptive statistics and logistic regression models were used to analyze the data. RESULTS: In the 10-year study period, 41 of 294 patients (13.9%; 95% confidence interval 10.2% to 18.4%) with symptoms after high-concentration peroxide ingestion demonstrated evidence of embolic events, and 20 of 294 (6.8%; 95% confidence interval 4.2% to 10.3%) either died or exhibited continued disability when the poison center chart was closed. Improved outcomes were demonstrated after early hyperbaric oxygen therapy. Endoscopy revealed grade 3 or 4 lesions in only 5 cases. CONCLUSION: Symptomatic high-concentration peroxide exposures had a high incidence of associated embolic events in this cohort. Patients with evidence of embolic events had a high rate of death. Early hyperbaric oxygen therapy may be useful, but routine endoscopy is unlikely to be of benefit1206953 field[33]: Not in FileB?@Havenith, T. Burger, D. Visschers, M. Schippers, J. Lashof, A.O.2017hAcute kidney injury following efavirenz/tenofovir disoproxil fumarate/emtricitabine (Atripla®) overdoseTherapeutic Drug Monitoring/online early: doi: 10.1097/FTD.0000000000000386not published, 01 Mar 179ACUTE Acute kidney injury acute renal failure ANTIVIRAL CLEARANCE CLINICAL CONCENTRATIONS dose DRUG drugs EFAVIRENZ emtricitabine FAILURE Fixed hemodialysis injuries Injury KIDNEY kidney injury NEPHROTOXICITY OVERDOSE PATIENT pharmacokinetic PHARMACOKINETICS PLASMA RENAL RENAL FAILURE safe SOFTWARE Tenofovir use 2/20/2017We describe a patient with acute renal failure and irreversible kidney damage after an overdose with the fixed dose combination of efavirenz/tenofovir disoproxil fumarate/emtricitabine (Atripla). The acute kidney injury was most probably caused by tenofovir. Efavirenz and emtricitabine seemed relatively safe in overdose. The pharmacokinetics in overdose of all three drugs and the effect of hemodialysis on the tenofovir clearance were studied by measuring the plasma concentrations and by the use of clinical pharmacokinetic software121118. field[33]: Not in File B?GHenstra, M. Wong, L. Chahbouni, A. Swart, N. Allaart, C. Sombogaard, F.2017Toxicokinetics of ibogaine and noribogaine in a patient with prolonged multiple cardiac arrhythmias after ingestion of internet purchased ibogaineClinical Toxicology0online early: doi: 10.1080/15563650.2017.1287372not published, 03 Mar 17sagent ARRHYTHMIA Arrhythmias As ATRIAL TACHYCARDIA CARDIAC CARDIAC ARRHYTHMIA CARDIOTOXICITY CLINICAL CONCENTRATIONS DEATH dependence DISTRIBUTION DRUG DRUG DEPENDENCE duration IBOGAINE INGESTION INTERNET IS KINETICS Long term Long-term MANAGEMENT METABOLITE PATIENT PERIPHERAL PLASMA Plasma levels QTc TACHYCARDIA TOXICOKINETIC toxicokinetics use VENTRICULAR TACHYCARDIA2/9/2017Background: Ibogaine is an agent that has been evaluated as an unapproved anti-addictive agent for the management of drug dependence. Sudden cardiac death has been described to occur secondary to its use. We describe the clinical effects and toxicokinetics of ibogaine and noribogaine in a single patient. For this purpose, we developed a LC-MS/MS-method to measure ibogaine and noribogaine plasma-concentrations. We used two compartments with first order absorption.Case details: The maximum concentration of ibogaine was 1.45 mg/L. Our patient developed markedly prolonged QTc interval of 647ms maximum, several multiple cardiac arrhythmias (i.e., atrial tachycardia and ventricular tachycardia and Torsades des Pointes). QTc-prolongation remained present until 12 days after ingestion, several days after ibogaine plasma-levels were low, implicating clinically relevant noribogaine concentrations long after ibogaine had been cleared from the plasma. The ratio k12/k21 for noribogaine was 21.5 and 4.28 for ibogaine, implicating a lower distribution of noribogaine from the peripheral compartment into the central compartment compared to ibogaine.Conclusions: We demonstrated a linear relationship between the concentration of the metabolite and long duration of action, rather than with parent ibogaine. Therefore, after (prolonged) ibogaine ingestion, clinicians should beware of long-term effects due to its metabolite121161/ field[33]: Not in File:?JWHikiji, W. Okumura, Y. Matsumoto, T. Tanifuji, T. Suzuki, H. Takeshima, T. Fukunaga, T.2016[Identification of psychotropic drugs attributed to fatal overdose – A case-control study by data from the Tokyo Medical Examiner's Office and prescriptions]3-13Seishin Shinkeigaku Zasshi1181analysis As CALCIUM case case-control case-control study COMPARISON DATA DEATH DRUG drug overdose drugs FATAL FLUNITRAZEPAM HEALTH IS LEVOMEPROMAZINE Medicine OVERDOSE PENTOBARBITAL PSYCHOTROPIC DRUGS PUBLIC PUBLIC HEALTH RISK STUDY USAGE2016:Drug overdose is a serious public health issue and fatal cases have been reported from various fields of medicine. This case-control analysis assessed the comparison between fatal overdose cases in the special wards of Tokyo Metropolitan area and prescribed psychotropic drugs in Tokyo in 2009-2010. It was suggested that the prescribed drugs serve as a direct cause of death in overdose cases. Furthermore, pentobarbital calcium, chlorpromazine-promethazine-phenobarbital, levomepromazine and flunitrazepam were identified as drugs with a high risk of fatal overdose. It is encouraged to prudently verify the intended application and usage of such psychotropic drugs in each case upon their prescription. This is the first study in Japan to identify psychotropic drugs with a high risk of fatal overdose by case-control study120837, field[22]: In Japanese with English abstract Not in FileB?/Hirashima, R. Itoh, T. Tukey, R.H. Fujiwara, R.2017;Prediction of drug-induced liver injury using keratinocytesJournal of Applied Toxicology#online early: doi: 10.1002/jat.3435not published, 16 Feb 17zAdverse Adverse drug reaction adverse drug reactions As DATA DICLOFENAC DILI DRUG drug induced liver injury drug-induced Drug-induced liver injury drugs GENE EXPRESSION Hepatotoxic HEPATOTOXICITY HUMAN INDUCTION injuries Injury IS john LEVELS LIVER liver injury MICE mouse PIOGLITAZONE PREDICTION PROTEIN PRURITUS RASH REACTIONS RISK SKIN Skin toxicity STUDY Toxicities TOXICITY 1/31/2017dDrug-induced liver injury (DILI) is one of the most common adverse drug reactions. DILI is often accompanied by skin reactions, including rash and pruritus. However, it is still unknown whether DILI-associated genes such as S100 calcium-binding protein A and interleukin (IL)-1beta are involved in drug-induced skin toxicity. In the present study, most of the tested hepatotoxic drugs such as pioglitazone and diclofenac induced DILI-associated genes in human and mouse keratinocytes. Keratinocytes of mice at higher risk for DILI exhibited an increased IL-1beta basal expression. They also showed a higher inducibility of IL-1beta when treated by pioglitazone. Mice at higher risk for DILI showed even higher sums of DILI-associated gene basal expression levels and induction rates in keratinocytes. Our data suggest that DILI-associated genes might be involved in the onset and progression of drug-induced skin toxicity. Furthermore, we might be able to identify individuals at higher risk of developing DILI less invasively by examining gene expression patterns in keratinocytes. Copyright (c) 2017 John Wiley & Sons, Ltd120737" field[33]: Not in FileB?(Hojerova, J. Perackova, Z. Berankova, M.2017Margin of safety for two UV filters estimated by in vitro permeation studies mimicking consumer habits: effects of skin shaving and sunscreen reapplicationFood and Chemical Toxicology,online early: doi: 10.1016/j.fct.2017.02.013not published, 01 Mar 17ABSORPTION Benefits BIOAVAILABILITY COSMETIC Cosmetics DERMAL Development DOE dose EXPOSURE Exposure scenario Guidelines IN VITRO Margin of safety PERCUTANEOUS RISK safe SAFETY SKIN STUDY SUNSCREEN SYSTEMIC 2/16/2017@Sunscreens are intended to work on the skin. To be both efficient and safe, the lowest possible percutaneous permeation of UV filters should occur. The potential for systemic absorption of Benzophenone-3 (BP3, 10%) and Ethylhexyl Triazone (EHT, 5%) in a silicone-based water-in-oil emulsion was assessed in vitro using a fullthickness porcine-ear skin mimicking in-use conditions. The estimated Systemic Exposure Dose (SED) after the sunscreen application at 1.0 mg/cm2 for 6 h (i) on the face; (ii) on the whole-body skin, was (i) 136 and 30; (ii) 4200 and 933 mug/kg_bw/d for BP3 and EHT, respectively. Reapplication does not mean the double risk; the SED values were only 1.40-1.37-fold greater. Skin shaving increased BP3 and EHT bioavailability 1.38 and 1.80-fold, respectively. Margin of Safety values were estimated according to guidelines applicable for European Union. For three realistic exposure scenarios, MoS of 48, 34 and 34 for BP3 in the sunscreen applied on the whole-body indicate some concerns regarding the safety for consumers (MoS<100). Despite undeniable functional benefits in sunscreens, BP3 concentration allowed in EU cosmetics (max. 10%) should be reviewed, especially in products intended for whole-body applications. The development of new UV filters should be focused on their specific physico-chemical properties121009+ field[33]: Not in FileB?Holland, M.G. Ferner, R.E.2017\A systematic review of the evidence for acute tolerance to alcohol – the "Mellanby effect"Clinical Toxicology0online early: doi: 10.1080/15563650.2017.1296576not published, 14 Mar 17ABSTRACT ACUTE ALCOHOL analysis As ASSESSMENT BLOOD Blood alcohol concentration DATA DATABASE dose DRIVING ETHANOL evidence family history HUMAN INTOXICATION IS LIMB MEDLINE men method methods NO Qualitative REVIEW safe scopus STUDY systematic review Time TOLERANCE TRIAL3/9/2017 Objective: To review the evidence for "the Mellanby effect", that is, whether the response to a given blood alcohol concentration (BAC) is more marked when BAC is rising than at the same concentration when BAC is falling. Methods: We systematically searched the databases EMBASE, Medline, and Scopus up to and including December 2016 using text words "tolerance", "ascending", "descending" or "Mellanby" with Medline term "exp *alcohol/" or "exp *drinking behavior/" or equivalent. Articles were identified for further examination by title or abstract; full text articles were retained for analysis if they dealt with acute (within dose) alcohol tolerance in human subjects and provided quantitative data on both the ascending and descending parts of the BAC–time curve. Reference lists of identified works were scanned for other potentially relevant material. We extracted and analyzed data on the subjective and objective assessment of alcohol effects. Results: We identified and screened 386 unique articles, of which 127 full-text articles were assessed; one provided no qualitative results, 62 involved no human study, 25 did not consider acute tolerance within dose, and 13 failed to provide data on both ascending and descending BAC. We extracted data from the 26 remaining articles. The studies were highly heterogeneous. Most were small, examining a total of 770 subjects, of whom 564 received alcohol and were analyzed in groups of median size 10 (range 5–38), sometimes subdivided on the basis of drinking or family history. Subjects were often young white men. Doses of alcohol and rates of administration differed. Performance was assessed by at least 26 different methods, some of which measured many variables. We examined only results of studies which compared results for a given alcohol concentration (C) measured on the ascending limb (Cup) and the descending limb (Cdown) of the BAC-time curve, whether in paired or parallel-group studies. When subjects were given alcohol in more than one session, we considered results from the first session only. Rating at Cdown was better than at Cup for some measures, as expected if the Mellanby effect were operating. For example, subjects rated themselves less intoxicated on the descending limb than at the same concentration on the ascending limb in 12/13 trials including 229 subjects that gave statistically significant results. In 9 trials with a total of 139 subjects, mean difference could be calculated; weighted for study size, it was 29% [range 24–74%]. Willingness to drive was significantly greater in 4 of 6 studies including a total of 105 subjects; weighted mean difference increased by 207% [range 79–300%]. By contrast, measure of driving ability in three groups of a total of 200 trials in 57 subjects showed worse performance by a weighted mean of 96% [range 3–566%]. In three trials that tested inhibitory control (cued go or no-go response times), weighted mean performance was 30% [range 14–65%] worse on the descending limb. Conclusions: The "Mellanby effect" has been demonstrated for subjective intoxication and willingness to drive, both of which are more affected at a stated ethanol concentration when BAC is rising than at the same concentration when BAC is falling. By contrast, objective measures of skills necessary for safe driving, such as response to inhibitory cues and skills measured on driving simulators, were generally worse on the descending part of the BAC-time curve for the same BAC.121185/ field[33]: Not in File B?"Hopkins, J. Pardo, M. Bischoff, K.2017dSerotonin syndrome from 5-hydroxytryptophan supplement ingestion in a 9-month-old labrador retrieverJournal of Medical Toxicology,online early: doi: 10.1007/s13181-017-0600-1not published, 01 Mar 175-HTP Agitation AIDS anemia ANTAGONIST ANTIEMETIC anxiolytic As case CASE REPORT Case-report CHEMISTRY CREATINE CYPROHEPTADINE dog EDUCATION EMBOLISM EMESIS ERYTHROCYTE evidence FEMALE GASTROINTESTINAL HEINZ BODIES hemolytic anemia HUMAN HYDROGEN HYDROGEN PEROXIDE HYPERBILIRUBINEMIA HYPERTENSION HYPERTHERMIA INFUSION INGESTION IS LEAD MANNITOL Medicine METABOLISM over the counter OVERDOSE PATIENT Peroxide PRECURSOR SEROTONIN SEROTONIN SYNDROME Syndrome TACHYCARDIA THERAPY toxic TREATMENT use Veterinary 2/16/2017XINTRODUCTION: 5-Hydroxytryptophan (5-HTP) supplements are available over the counter and labeled as sleeping aids and anxiolytics for human use. 5-HTP is a serotonin precursor and overdose can lead to serotonin syndrome. CASE REPORT: A 9-month-old female Labrador retriever was evaluated after ingestion of a 5-HTP supplement. Signs of agitation developed within 1 h of ingestion, and emesis was attempted by the owner with 3% hydrogen peroxide (H2O2) orally. On presentation, the dog was obtunded, bilaterally mydriatic and salivating. Physical exam revealed tachypnea, tachycardia, hyperthermia, and hypertension. Eighteen hours post presentation, the dog developed melena, hematemesis, and pigmenturia. A hemogram revealed mild anemia with evidence of oxidative erythrocyte damage (eccentrocytes, Heinz bodies, and siderocytes). A chemistry panel revealed markedly elevated creatine kinase and hyperbilirubinemia, supporting hemolytic anemia. A urinalysis revealed pigmenturia. Hemolytic anemia was presumed to be caused by oxidative damage secondary to gastrointestinal ulceration and circulatory embolism of H2O2. Treatment included fluid therapy, a mannitol constant rate infusion, antiemetics, gastroprotectants, and cyproheptadine as a serotonin antagonist. The patient responded well to treatment and was discharged within 48 h of presentation. DISCUSSION: Serotonin syndrome is an increasingly common toxic syndrome in veterinary medicine with the availability of over-the-counter medications that alter serotonin metabolism. The importance of appropriate client education regarding emesis with H2O2 is highlighted121051+ field[33]: Not in FileB? Horowski, R.2017@The "madness" of Friedrich Holderlin: an iatrogenic intoxicationJournal of Neural Transmission,online early: doi: 10.1007/s00702-017-1689-8not published, 28 Feb 18RGERMAN HAIR HI IATROGENIC INTOXICATION MERCURY NEUROLOGICAL SCHIZOPHRENIA SYMPTOMS2/7/2017The German poet Holderlin, assumed to have suffered from schizophrenia, in fact has been the victim of a combined calomel and cantharidine intoxication administered by his physician Autenrieth. This new theory explains much better his behavioural changes and also his neurological and other concomitant symptoms; it can be tested by analysing a very few of his hairs for the presence of these compounds120901+ field[33]: Not in File ?MHuang, D. Wu, S. Hou, X. Jia, L. Meng, Q. Chu, H. Jiang, J. Shang, L. Hao, W.2017YThe skeletal developmental toxicity of chlormequat chloride and its underlying mechanisms1-9 Toxicology381/analysis ANIMAL Animals BLOOD Body Weight BONE CHLORMEQUAT Development DEVELOPMENTAL Developmental toxicity dose EXPOSURE GROWTH GROWTH FACTOR GROWTH HORMONE HORMONE impact INSULIN MALE MECHANISM Mechanisms mRNA expression PLANT PLANT GROWTH REGULATOR POSTNATAL RAT rats STUDY Toxicities TOXICITY WEIGHT 2/15/2017\Chlormequat Chloride (CCC), a widely used plant growth regulator, could decrease body weight in animals; however, the mechanism has not been well studied. This study was designed to evaluate the skeletal development toxicity of CCC on pubertal male Sprague-Dawley (SD) rats and to investigate whether CCC impacts the development of chondrocyte, osteoblast and osteoclast through growth hormone (GH) and insulin like growth factor 1 (IGF-I). Rats from 23 to 70 on postnatal days were exposed to CCC daily by gavage at doses of 0, 75, 150, and 300mg/kg bw/d. The results showed that the size of femurs and tibias, bone mineral density and biomechanical parameters were significantly decreased in the 300mg/kg bw/d group compared with the control group. The concentration of osteocalcin (OCN) and C-terminal telopeptide of type I collagen (CTX-I) in blood in the 150mg/kg bw/d group was also changed. The mRNA expression ratio of the receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) in 150 and 300mg/kg bw/d group was increased. Histological analysis of proximal and distal epiphyseal plates of the right femurs showed that both the proliferative zone and hypertrophic zone narrowed in CCC-treated groups. The concentration of IGF-I in blood was reduced with an increase in exposure doses of CCC. The mRNA expression of growth hormone receptor (GHR) in tibia was decreased in the CCC-treated group. The results indicated that CCC might indirectly impact the formation and activation of chondrocytes, osteoblasts and osteoclasts because of the decline of GHR and IGF-I, leading to skeletal development damage121132+ field[33]: Not in FileJB?>Huang, Y. He, C. Shen, C. Guo, J. Mubeen, S. Yuan, J. Yang, Z.2017IToxicity of cadmium and its health risks from leafy vegetable consumptionFood & Function%online early: doi: 10.1039/C6FO01580Hnot published, 01 Mar 17FAs CADMIUM Cd Consumption CONTAMINATION DIETARY Dietary supplement Dietary supplements Environment EXPOSURE HEALTH Health risk Health risks Heavy metal HUMAN Humans Intake IS Knowledge OCCUPATIONAL OCCUPATIONAL EXPOSURE Pathway POLLUTION Reference areas REVIEW RISK Source toxic Toxicities TOXICITY Vegetables vitamin VITAMINS 2/24/2017Cadmium (Cd) is a highly toxic heavy metal and has spread widely in the environment in recent decades. This review summarizes current knowledge about Cd contamination of leafy vegetables, its toxicity, exposure, health risks, and approaches to reducing its toxicity in humans. Leafy vegetable consumption has been identified as a dominant exposure pathway of Cd in the human body. An overview of Cd pollution in leafy vegetables as well as the main sources of Cd is given. Notable estimated daily intakes and health risks of Cd exposure through vegetable consumption for humans are revealed in occupational exposure areas and even in some reference areas. Vegetable consumption is one of the most significant sources of exposure to Cd, particularly in occupational exposure regions. Therefore, numerous approaches have been developed to minimize the accumulation of Cd in leafy vegetables, among which the breeding of Cd pollution-safe cultivars is one of the most effective tools. Furthermore, dietary supplements from leafy vegetables perform positive roles in alleviating Cd toxicity in humans with regard to the effects of essential mineral elements, vitamins and phytochemicals taken into the human body via leafy vegetable consumption121007$ field[33]:!divAbstract Not in FileB?Hui-Jun, H. Dan-Feng, F.2017DShould hyperbaric oxygen be used in acute carbon monoxide poisoning?&American Journal of Emergency Medicine-online early: doi: 10.1016/j.ajem.2017.02.027not published, 01 Mar 17ACUTE carbon CARBON MONOXIDE carbon monoxide poisoning HYPERBARIC OXYGEN hyperbaric oxygen therapy OXYGEN POISONING THERAPY TREATMENT 2/13/2017120936, field[33]: Not in File +B?THussain, S.A. Tsao, J. Li, M. Schwarz, M.D. Zhou, R. Wu, J.Y. Salamon, N. Sankar, R.2017oRisk of vigabatrin-associated brain abnormalities on MRI in the treatment of infantile spasms is dose-dependent Epilepsia$online early: doi: 10.1111/epi.13712not published, 01 Mar 17Canalysis As Association Attention BASAL GANGLIA BRAIN Brain MRI CHILDREN Cohort DATA DOSAGE EXPOSURE Hormonal therapy HORMONE Imaging impact IS Knowledge MAGNETIC RESONANCE magnetic resonance imaging method methods MRI NEUROTOXICITY P PAEDIATRIC PATIENT PREDNISOLONE RISK STUDY SYMPTOMS THERAPY TREATMENT use VIGABATRIN WHO 2/23/2017OBJECTIVE: Although the link between vigabatrin (VGB) and retinotoxicity is well known, little attention has been focused on the risk of VGB-associated brain abnormalities on magnetic resonance imaging (MRI) (VABAM), namely reversible-and largely asymptomatic-signal changes in the thalami, basal ganglia, brainstem tegmentum, and cerebellar nuclei. Using a large infantile spasms cohort, we set out to identify predictors of these phenomena. METHODS: Children with infantile spasms were retrospectively identified. Brain MRI reports were serially reviewed without knowledge of VGB exposure. Upon VABAM discovery, records were systematically reviewed to ascertain presence of symptoms attributable to VGB. Separately, progress notes were sequentially reviewed to identify and quantify VGB exposure. RESULTS: We identified 507 brain MRI studies among 257 patients with infantile spasms. VGB treatment was documented in 143 children, with detailed exposure data available for 104, of whom 45 had at least one MRI study during VGB treatment. Among the limited subset of asymptomatic children who underwent MRI (n = 40), 6 exhibited VABAM. Risk of asymptomatic VABAM was dose-dependent, as peak (but not cumulative) VGB dosage was strongly associated with asymptomatic VABAM (p = 0.0028). In an exploratory analysis, we encountered 4 children with symptomatic VABAM among 104 patients with detailed VGB exposure data. Risk of symptomatic VABAM was seemingly dose-independent, and potentially associated with concomitant hormonal therapy (i.e., prednisolone and adrenocorticotropic hormone [ACTH]) (p = 0.039). SIGNIFICANCE: We have demonstrated dose-dependent risk of asymptomatic VABAM and uncovered a possible association between symptomatic VABAM and concomitant hormonal therapy. Caution should be exercised in the use of high VGB dosage (i.e., >175 mg/kg/day), and further study is warranted to confirm the potential impact of hormonal therapy120997# field[33]: Not in File?Ifegwu, O.C. Anyakora, C.20152Polycyclic aromatic hydrocarbons: part I. Exposure277-304Advances in Clinical Chemistry72AROMATIC HYDROCARBONS carcinogenic CARCINOGENICITY chemical CHEMICALS DNA EXPOSURE genotoxic HUMAN Humans HYDROCARBON IS PAH POLYCYCLIC AROMATIC HYDROCARBONS REVIEW SOFT TISSUE SYNERGIST teratogenic TISSUE tumor use2015Polycyclic aromatic hydrocarbons (PAH) comprise the largest class of cancer-causing chemicals and are ranked ninth among chemical compounds threatening to humans. Although interest in PAH has been mainly due to their carcinogenic property, many of these compounds are genotoxic, mutagenic, teratogenic, and carcinogenic. They tend to bioaccumulate in the soft tissues of living organisms. Interestingly, many are not directly carcinogenic, but act like synergists. PAH carcinogenicity is related to their ability to bind DNA thereby causing a series of disruptive effects that can result in tumor initiation. Thus, any structural attribute or modification of a PAH molecule that enhances DNA cross linking can cause carcinogenicity. In part I, we review exposure to these dangerous chemicals across a spectrum of use in the community and industry. Copyright © 2015 Elsevier Inc. All rights reserved120817, field[33]: Not in File ?WIsmail, A.A. Bonner, M.R. Hendy, O. Abdel Rasoul, G. Wang, K. Olson, J.R. Rohlman, D.S.2017hComparison of neurological health outcomes between two adolescent cohorts exposed to pesticides in Egypte0172696PLoS ONE122ADOLESCENT Adolescents APPLICATOR As BLOOD Blood samples BRAIN CHOLINESTERASE Cohort COMPARISON COTTON DEPRESSION evidence EXPOSURE HEALTH impact Inhibition IS MALE neurobehavioral neurobehavioral tests NEUROLOGICAL neurotoxic neurotoxic effects NEUROTOXICITY NO organophosphorus outcome P PAEDIATRIC pesticide PESTICIDES POISONING PYRETHROID QUESTIONNAIRE RISK Rural SCREENING SERUM STUDY SYMPTOMS TEST Time2017 Pesticide-exposed adolescents may have a higher risk of neurotoxic effects because of their developing brains and bodies. However, only a limited number of studies have addressed this risk among adolescents. The aim of this study was to compare neurological outcomes from two cohorts of Egyptian adolescents working as pesticide applicators. In 2005 and 2009, two cohorts of male adolescents working as pesticide applicators for the cotton crop were recruited from Menoufia Governorate, Egypt. The same application schedule and pesticides were used at both times, including both organophosphorus, and pyrethroid compounds. Participants in both cohorts completed three neurobehavioral tests, health and exposure questionnaires, and medical and neurological screening examinations. In addition, blood samples were collected to measure butyryl cholinesterase (BChE) activity. Pesticide applicators in both cohorts reported more neurological symptoms and signs than non-applicators, particularly among participants in the 2005 cohort (OR ranged from 1.18 to 15.3). Except for one test (Trail Making B), there were no significant differences between either applicators or non-applicators of both cohorts on the neurobehavioral outcome measures (p > 0.05). The 2005 cohort showed greater inhibition of serum BChE activity than the 2009 cohort (p < 0.05). In addition, participants with depressed BChE activity showed more symptoms and signs than others without BChE depression (p < 0.05). Our study is the first to examine the consistency of health outcomes associated with pesticide exposure across two cohorts tested at different times from the same geographical region in rural Egypt. This similar pattern of findings across the two cohorts provides strong evidence of the health impact of exposure of adolescents to pesticides121091. field[33]: Not in File B?/Jain, S. Srivastava, A.S. Verma, R.P. Maggu, G.2017KCaffeine addiction: need for awareness and research and regulatory measuresAsian Journal of Psychiatry,online early: doi: 10.1016/j.ajp.2017.01.008not published, 28 Feb 17MABUSE ADDICTION As Awareness CAFFEINE case CHILDREN Consumption Content dependence family harm Harms HAZARD HEALTH Health hazard health hazards Impulsivity India INDIUM INTOXICATION IS Knowledge LEGAL limits PATIENT PSYCHIATRIC PSYCHOLOGICAL PSYCHOSIS PUBLIC PUBLIC HEALTH Regulatory RESEARCH SAFETY School SOCIAL SURVEY SYMPTOMS use2/4/2017Caffeine consumption has been constantly growing in India especially among children and youngsters. Addictive potential of caffeine has long been reported, still there is lack of awareness about caffeine abuse in India. There is an intense need for appropriate public health regulatory measures and awareness about addictive potential & harms related to caffeine. To the best of our knowledge this is first case from India highlighting several important issues with progressive caffeine abuse resulting in dependence leading to physical, psychological, academic and social consequences; psychotic symptoms during intoxication; predisposing factors as impulsivity and novelty seeking traits in pre-morbid personality; psychosis in family; poor awareness of health hazards even among medical professionals. Widely variable caffeine containing products are available but caffeine content or its safety limit is not mentioned on caffeine products in India. Due to harmful consequences, legal availability to children, growing consumption of caffeine products, it is utmost essential to recognize caffeine as addictive substance and impose regulatory measures on sale, advertisement, maximum caffeine content, health consequences and safety limits of caffeine containing products. Further school teachers, parents and medical practitioners need to be made aware of health hazards of caffeine. Caffeine use shall always be enquired from patients presenting with psychiatric complaints. Further research and survey are required on caffeine use and related problems120855+ field[33]: Not in File?JJalalzadeh, M. Ghadiani, M.H.2016HKidney failure due to abdominal compartment syndrome following snakebite66-69"Iranian Journal of Kidney Diseases111Abdomen ACUTE acute kidney failure ANTIVENIN As case CASE REPORT Case-report COMPARTMENT SYNDROME complications FAILURE hemolysis HYPERTENSION IS KIDNEY Kidney failure NEPHROTOXICITY RHABDOMYOLYSIS snake bite SNAKEBITE Syndrome TREATMENT1/2016Treatment of snakebite complications is challenging, as it is difficult to distinguish what kind of antivenins should be used. Kidney failure as a result of rhabdomyolysis or hemolysis may happen due to accumulated fluids that increase the pressure in the abdomen. This case report describes acute kidney failure probably due to intra-abdominal hypertension following an unknown bite1208918 Not in File ^B?GJang, D.H. Kelly, M. Hardy, K. Lambert, D.S. Shofer, F.S. Eckmann, D.M.2017A preliminary study in the alterations of mitochondrial respiration in patients with carbon monoxide poisoning measured in blood cellsClinical Toxicology0online early: doi: 10.1080/15563650.2017.1288912not published, 03 Mar 17As Biomarker BIOMARKERS BLOOD carbon CARBON MONOXIDE carbon monoxide poisoning CELL CLINICAL CO CYTOCHROME CYTOCHROME C OXIDASE DEATH Deaths EXPOSURE GA GAS ILLNESS Inhibition IS IV LACTATE LEVELS Measurement method Mitochondrial respiration MORBIDITY MORTALITY NO outcome PATIENT PERIPHERAL POISONING PROGNOSIS RESPIRATION RESPIRATORY SEVERITY STUDY TERTIARY CARE THERAPY Time UNITED STATES use 2/16/2017SObjectives: Carbon monoxide (CO) is a colorless and odorless gas responsible for poisoning mortality and morbidity in the United States. At this time, there is no reliable method to predict the severity of poisoning or clinical prognosis following CO exposure. Whole blood cells, such as peripheral blood mononuclear cells (PBMCs) and platelets, have been explored for their potential use to act as sensitive biomarkers for mitochondrial dysfunction which may have a role in CO poisoning.Design: The objective of this study was to measure mitochondrial respiration using intact cells obtained from patients exposed to CO as a potential biomarker for mitochondrial inhibition with results that can be obtained in a time frame useful for guiding clinical care. This was a prospective, observational pilot study performed from July 2015 to July 2016 at a single academic tertiary care center that is the location of the region's only multi chamber hyperbaric.Measurements: Clinical characteristics, patient demographics, mitochondrial respiration and outcomes were recorded.Main results: There were 7 patients enrolled with a mean COHb level 26.8 ± 10 and with a mean lactate of 1.1 ± 0.4 mmol/L. All 7 CO exposures were related to heat generators used during winter months with two deaths. There was a positive correlation between maximal respiration and COHb levels with both high maximal respiration and high spare respiratory capacity correlating with a high COHb level. There was a subset of PBMCs (n = 4) that were analyzed for Complex IV (cytochrome c oxidase) activity.Conclusions: In this pilot study, measurements can be performed in an appropriate timeline for clinical care with potential to serve as a prognostic marker. Further work is necessary to develop high-resolution respirometry as a clinical tool for assessing the severity of illness and guiding therapy121151/ field[33]: Not in File B?Jansson, L.M. Velez, M. McConnell, K. Spencer, N. Tuten, M. Jones, H.E. King, V.L. Gandotra, N. Milio, L.A. Voegtline, K. DiPietro, J.A.2017FMaternal buprenorphine treatment and fetal neurobehavioral development-American Journal of Obstetrics and Gynecology-online early: doi: 10.1016/j.ajog.2017.01.040not published, 28 Feb 17ACUTE Affect analysis As baseline Benefits BUPRENORPHINE CARDIAC COMPARISON DATA DEPRESSION Development DEVELOPMENTAL dose FACILITIES FETAL Gestational HEART Heart Rate INFANT Infants IS LEVELS Longitudinal medication assisted treatment METHADONE MONITORING motor neurobehavioral OPIOID opioid use disorder outcome PREGNANCY Pregnancy outcome STUDY Substance use substance use disorder Time TREATMENT UNITED STATES use Variability WOMEN2/7/2017BACKGROUND: Gestational opioid use/misuse is escalating in the United States, however, little is understood about the fetal effects of medications used to treat maternal opioid use disorders. OBJECTIVE: The purpose of this study was to determine the effect of maternal buprenorphine administration on longitudinal fetal neurobehavioral development. STUDY DESIGN: Forty-nine buprenorphine-maintained women attending a substance use disorder treatment facility with generally uncomplicated pregnancies underwent fetal monitoring for 60 minutes at times of trough and peak maternal buprenorphine levels. Data were collected at 24, 28, 32, and 36 weeks gestation. Fetal neurobehavioral indicators (i.e., heart rate, motor activity and their integration (fetal movement-fetal heart rate coupling)) were collected via an actocardiograph, digitized and quantified. Longitudinal data analysis relied on hierarchical linear modeling. RESULTS: Fetal heart rate, heart rate variability and heart rate accelerations were significantly reduced at peak versus trough maternal buprenorphine levels. Effects were significant either by or after 28 weeks of gestation, and tended to intensify with advancing gestation. Fetal motor activity and fetal movement-fetal heart rate coupling were depressed from peak to trough at 36 weeks of gestation. Polysubstance-exposure did not significantly affect fetal neurobehavioral parameters, with the exception that fetuses of heavier smokers moved significantly less than those of lighter smokers at 36 weeks. By the end of gestation, higher maternal buprenorphine dose was related to depression of baseline fetal cardiac measures at trough. CONCLUSIONS: Maternal buprenorphine administration has acute suppressive effects on fetal heart rate and movement, and the magnitude of these effects increases as gestation progresses. Higher dose (> 13 mg) appears to exert greater depressive effects on measures of fetal heart rate and variability. These findings should be balanced against comparisons to gestational methadone effects, relatively good outcomes of buprenorphine-exposed infants, and recognition of the benefits of medication assisted treatment for pregnant women with opioid use disorders in optimizing pregnancy outcomes120852, field[33]: Not in File R?3Jawien, W. Wilimowska, J. Klys, M. Piekoszewski, W.2017iPopulation pharmacokinetic modelling of valproic acid and its selected metabolites in acute VPA poisoning340-349Pharmacological Reports692ACID ACUTE acute intoxication analysis Antiepileptic BLOOD Blood samples CHROMATOGRAPHY CLINICAL DATA DECONTAMINATION dose DRUG EFFICACY EVALUATION EXPERIMENTAL HOSPITAL INFORMATION ingested INGESTION INTOXICATION IS KINETICS Liquid chromatography MASS SPECTROMETRY men METABOLITE Metabolites method methods MODEL OVERDOSE pharmacokinetic PHARMACOKINETICS POISONING Population PROTEIN Protein Binding Route seizure SEIZURES SPECTROMETRY STUDY THERAPY Time Time Course TREATMENT VALPROATE VALPROIC ACID WOMEN1/6/2017@BACKGROUND: Valproic acid (VPA) is a first-line antiepileptic drug. It is used in the treatment of many different types of partial and generalized epileptic seizures. Though the clinical pharmacokinetics of VPA has been well defined, information about pharmacokinetics after overdoses is rare. The aim of this study was to try to build a population pharmacokinetic model that would describe the time course of VPA and its selected metabolites when the drug is ingested in an overdose situation. METHODS: Blood samples were collected during admission to the hospital and several times during treatment for poisoning (10 men and 10 women). The concentration of VPA and its metabolites were determined by liquid chromatography coupled with mass spectrometry. For population pharmacokinetic evaluation of VPA and its metabolites, the two-compartment-model was applied. RESULTS: The estimated doses of VPA taken ranged from 6 to 65g, while the time after ingestion ranged from 1 to 30h. Results showed that the beta-oxidation process exhibited Michaelis-Menten kinetics becoming saturated during acute intoxication. The same could not be said for the desaturation route. VPA therapy increased the Vmax for beta-oxidation by 59% while decontamination appeared to be of moderate efficacy lowering the F value by 34% on the average. CONCLUSIONS: None of the models perfectly described the experimental data. Important factors like the variable degree of protein binding by VPA could not be included in the models. The small number of subjects used in the study made the analysis of more covariates impossible120918. field[33]: Not in File B?qJensen, V.F.H. Mølck, A.-M. Berthelsen, L.O. Alifrangis, L. Andersen, L. Chapman, M. Lykkesfeldt, J. Bøgh, I.B.2017oToxicological effects during and following persistent insulin-induced hypoglycaemia in healthy euglycaemic ratsBasic Clin Pharmacol Toxicol%online early: doi: 10.1111/bcpt.12769not published, 01 Mar 17rAdipose Tissue ANIMAL Animals As Atrophy Body Weight Consumption Development duration EFFICACY FOOD Guidelines HYPERGLYCAEMIA HYPOGLYCAEMIA INFUSION INSULIN interpretation IS LEVELS MUSCLE NERVE Nonclinical studies pancreatic PATIENT PERIPHERAL pharmacokinetic RAT rats Regulatory Reversibility reversible SAFETY SKELETAL MUSCLE STUDY TISSUE transient WEIGHT Weight Loss 2/20/2017New insulin analogues with a longer duration of action and a "peakless" pharmacokinetic profile have been developed to improve efficacy, safety and convenience for diabetic patients. During non-clinical development, according to regulatory guidelines, these analogues are tested in healthy euglycaemic rats rendering them persistently hypoglycaemic. Little is known about the effect of persistent (24 hr/day) insulin-induced hypoglycaemia (IIH) in rats, complicating interpretation of results in pre-clinical studies with new longer-acting insulin analogues. In the present study, we investigated the effects of persistent IIH and their reversibility in euglycaemic rats. Histopathological changes in insulin-infused animals included partly reversible axonal and reversible myofibre degeneration in peripheral nerve and skeletal muscle tissue, respectively, as well as reversible pancreatic islet atrophy and partly reversible increase in unilocular adipocytes in brown adipose tissue. Additionally, results suggested increased gluconeogenesis. The observed hyperphagia, the pancreatic, peripheral nerve and skeletal muscle changes were considered related to the hypoglycaemia. Cessation of insulin infusion resulted in transient hyperglycaemia, decreased food consumption and body weight loss before returning to control levels. The implications for the interpretation of non-clinical studies with long-acting insulin analogues are discussed. This article is protected by copyright. All rights reserved120948$ field[33]: Not in File ,?BJin, F. Wan, C. Li, W. Yao, L. Zhao, H. Zou, Y. Peng, D. Huang, W.2017aFormononetin protects against acetaminophen-induced hepatotoxicity through enhanced NRF2 activitye0170900PLoS ONE122cACETAMINOPHEN ACUTE ALANINE ANTIOXIDANT apoptosis ASSAY CELL Content DATA EXPERIMENTAL EXPOSURE GENE EXPRESSION GLUTATHIONE GSH HEPATIC HEPATOTOXICITY HISTOPATHOLOGY HUMAN IN VITRO IN VIVO INJECTION injuries Injury INTRAPERITONEAL LEVELS LIVER liver injury MALE MDA MICE Nrf2 OVERDOSE P PARACETAMOL PATIENT PRETREATMENT PROTEIN SERUM TREATMENT use Vehicle2017To examine the effects of formononetin (FMN) on Acetaminophen (APAP)-induced liver injury in vitro and in vivo. Human non-tumor hepatic cells LO2 were pretreated with either vehicle or FMN (20, 40 muM), for 6 h, followed by incubation with or without APAP (10 mM) for 24 h. In an in vivo assay, male BALB/c mice were randomly divided into four groups: (1) control group; (2) APAP group; (3) APAP + FMN (50 mg/Kg); (4) APAP + FMN (100 mg/Kg). The mice in the control and APAP groups were pre-treated with vehicle; the other two groups were pretreated daily with FMN (50, 100 mg/Kg) orally for 7 consecutive days. After the final treatment, acute liver injury was induced in all groups, except the control group, by intraperitoneal (i.p.) injection of 300 mg/Kg APAP. In LO2 cells, APAP exposure decreased the cell viability and glutathione (GSH) content, which were both greatly restored by FMN pretreatment. Overdose of APAP increased hepatic malondialdehyde (MDA) content, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activity in experimental mice. Supplementation with 100 mg/Kg FMN significantly reduced APAP-induced elevated levels of MDA (1.97 +/- 0.27 vs 0.55 +/- 0.14 nmol/mg protein, p < 0.001), ALT (955.80 +/- 209.40 vs 46.90 +/- 20.40 IU/L, p < 0.001) and AST (1533.80 +/- 244.80 vs 56.70 +/- 28.80 IU/L, p < 0.001), and hepatic GSH level (5.54 +/- 0.93 vs 8.91 +/- 1.11 mumol/mg protein, p < 0.001) was significantly increased. These results were further validated by histopathology and TdT-mediated biotin-dUTP nick-endlabeling (TUNEL) staining, pretreatment with 100 mg/Kg FMN significant decreased APAP-induced hepatocellular damage and cell apoptosis (36.55 +/- 3.82 vs 2.58 +/- 1.80%, p < 0.001). Concomitantly, FMN stimulated the expression of Nrf2 and antioxidant gene expression in the presence of APAP. These data provide an experimental basis for the use of FMN in the treatment of patients with APAP-induced hepatotoxicity121092. field[33]: Not in File8?.Jochum, M. Oeding, J. Lackner, D. Lienhart, H.2017UEcstasy-Intoxikation mit disseminierter intravasaler Gerinnung und Multiorganversagen145-151.Anasthesiol Intensivmed Notfallmed Schmerzther522AMFETAMINE amphetamine As CANNABIS case CLINICAL Consumption DATA DRUG drugs ECSTASY history INTOXICATION IS lethal MDMA outcome PATIENT RESUSCITATION RISK TREATMENT2/2017This case presents the clinical treatment of a patient with severe MDMA intoxication. The history of stimulating psychotropic substances is presented as well as the modes of action of current party drugs. Data from the Austrian Drug Report indicate a tendency away from "hard drugs" towards the consumption of cannabis and amphetamine derivates. The lethal outcome in our case demonstrates the risk potential of these substances and underlines the necessity of aggressive resuscitation efforts120943' field[22]: [Ecstasy intoxication with disseminated intravascular coagulation and multiorgan failure]. In German with English abstract RefMgr field[33]: Not in FileB?(Johnson, J. Williams, K. Banner, W., Jr.2017#Adolescent with prolonged toxidromeClinical Toxicology0online early: doi: 10.1080/15563650.2017.1287912not published, 03 Mar 17ADOLESCENT As BEZOAR CLINICAL DIPHENHYDRAMINE Emergencies emergency EMERGENCY DEPARTMENT FEMALE INGESTION IS MANAGEMENT NO PAEDIATRIC PATIENT PHARMACOBEZOAR radiopacity REMOVAL RESUSCITATION S seizure SEIZURES SYMPTOMS Toxicities TOXICITY TOXICOKINETIC 2/13/2017A 13-year-old female was presented to the emergency department following an intentional ingestion. The patient developed significant toxicity including multiple, discreet tonic-clonic seizures. Despite appropriate resuscitation and antidotal management, the patient's symptoms persisted for more than 36 hours post-ingestion. An upright abdominal radiograph was performed revealing a radiopacity suggesting a pharmacobezoar. An esophagogastroduodenoscopy was performed with successful removal of a tennis ball-sized pharmacobezoar. The patient s symptoms subsequently subsided and she recovered fully with no neurologic deficits. Diphenhydramine has not been previously identified as a medication likely to form a pharmacobezoar and has not been shown to be radiopaque. Though bezoar formation is a rare clinical scenario, it is one that toxicologists must consider in patients with clinical courses that persist far beyond expected based on known toxicokinetic principles121146/ field[33]: Not in Filea?%Johnson, K. Stollings, J.L. Ely, E.W.2017cBreaking bad delirium: methamphetamine and boric acid toxicity with hallucinations and pseudosepsis138-141Southern Medical Journal1102^ACID ACUTE agent AMFETAMINE ANT ANTS ARSENIC As ASPIRIN BORIC ACID BRAIN CLINICAL cognitive COST DELIRIUM DEMENTIA EVALUATION HALLUCINATIONS HI HOSPITAL ILLNESS IMPAIRMENT INGESTION IS Long term Long-term Man MANAGEMENT Mechanical ventilation METHAMPHETAMINE MORTALITY Mouth PATIENT Poison PSYCHIATRIC SALICYLATE SHOCK Toxicities TOXICITY VENTILATION2/2017OBJECTIVES: A 30-year-old patient presented with hallucinations and profound shock. He was initially misdiagnosed as having severe sepsis; once ingestions were considered, he was diagnosed as potentially having arsenic toxicity. SUMMARY: The clinical story reveals many instructional lessons that could aid in the evaluation and management of future patients. This man presented with large amounts of blue crystals around his nose and lips from inhaling and eating boric acid (an ant poison) so he could, as he put it, kill the ants "pouring into my mouth and nose and up into my brain." His profound pseudosepsis and sustained delirium were induced by co-ingestion of methamphetamine and a large quantity of boric acid. Delirium is a form of acute brain dysfunction that often is multifactorial in critical illness and, when seen in septic shock, is associated with prolonged mechanical ventilation, increased length of hospital stay, medical costs, higher mortality, and long-term cognitive impairment resembling dementia. Pseudosepsis is a noninfectious condition most commonly seen with ingestions such as salicylate (aspirin) toxicity. CONCLUSIONS: This report emphasizes the need to recognize agents that contain boric acid as an etiology of unexplained delirium and profound shock120811/ field[33]: Not in FileKB?DJohnson, P.I. Sutton, P. Koustas, E. Vesterinen, H.M. Woodruff, T.J.2017Response to correspondence by Heather Lynch, Julie Goodman and Nancy Beck Re: "Application of the Navigation Guide systematic review methodology to the evidence for developmental and reproductive toxicity of triclosan"Environment International/online early: doi: 10.1016/j.envint.2017.02.007not published, 01 Mar 17xDEVELOPMENTAL evidence LETTER reproductive toxicity reprotoxicity REVIEW systematic review Toxicities TOXICITY TRICLOSAN 2/21/2017121011. field[33]: Not in File B?(Jordan, C.D. Korley, F.K. Stolbach, A.I.2017ZSelf-reported cocaine use is not associated with elevations in high-sensitivity troponin IClinical Toxicology0online early: doi: 10.1080/15563650.2017.1285404not published, 03 Mar 17ACUTE acute coronary syndrome ASSAY CARDIAC COCAINE Cohort CONCENTRATIONS CORONARY DOE IS LEAD METABOLITE NO PATIENT prevalence Syndrome Time TOXICOLOGY URINE urine toxicology use WHO2/9/2017Objective: High-sensitivity troponin (hsTn) assays detect 10 times lower concentrations of cardiac troponin than conventional assays. We examined the effects of self-reported cocaine use to determine whether those with acute cocaine use being evaluated for ACS are more likely to have elevated hsTnI than those nonusers being evaluated for ACS.Methods: We conducted a sub-analysis of a prospective cohort of ED patients evaluated for acute coronary syndrome. Recent cocaine use was determined by structured patient interviews. High-sensitivity troponin (Abbott) and conventional troponin I (Abbott, cTnI) were measured on samples drawn at presentation. Urine toxicology screen for cocaine metabolite was obtained at the discretion of treating clinicians.Results: Of 1862 patients enrolled, 444 reported prior cocaine use and 99 reported cocaine use within the preceding month. Median hsTn in patients with last cocaine use within 24 h, 2-7 days, 1 week-1 month, >1 month, and no prior cocaine use were: 9 (IQR: 3-17) ng/L, 6 (IQR: 3-24.3) ng/L, 6 (IQR: 3-89.5) ng/L, 3 (IQR: 3-18.5) ng/L and 3 (IQR: 3-17) ng/L, respectively. Urine toxicology assays (UTox) for cocaine were performed in 640 (34.4%) patients. The median hsTn for those who were UTox+, UTox – and those without a UTox were: 9 ng/L (IQR: 3–48.5), 9?ng/L (IQR: 3–40) and 3 ng/L (IQR: 3–12), respectively. There were no differences in the prevalence of new troponin elevations (hsTn >99th percentile but cTnI <99th percentile) in those with recent cocaine use compared to those without recent cocaine use.Conclusions: In this first investigation of hsTn in patients with self-reported recent cocaine use, we have determined that hsTn does not lead to an increase in the prevalence of troponin elevation in cocaine users121162/ field[33]: Not in FileV?[Jouhadi, Z. Bensabbahia, D. Chafiq, F. Oukkache, B. Guebessi, N.B. Abdellah, E.A. Najib, J.2016)Lead poisoning in children: a case report316Pan African Medical Journal24Abdomen Abdominal Pain ACUTE BLOOD Blood lead case CASE REPORT Case-report child CHILDREN Consumption DIAGNOSIS HEALTH IS LEAD Lead Poisoning LEVELS PAEDIATRIC pain PAINT PICA POISONING Population PUBLIC PUBLIC HEALTH RISK2016qLead colic is a rare cause of abdominal pain. The diagnosis of lead poisoning is most often mentioned in at risk populations (children, psychotic). We report the case of a 2 year old child that was presented for acute abdomen. Abdominal plain radiograph showed multiple intra-colonic metallic particles and suggested lead poisoning diagnosis. Anamnesis found a notion of pica and consumption of peeling paint. Elevated blood lead levels (BLL) confirmed the diagnosis. The lead poisoning is a public health problem especially in children, but its manifestation by a lead colic is rare and could simulate an acute abdomen table1207341 field[33]: Not in File B?4Juba, K.M. Khadem, T.M. Hutchinson, D.J. Brown, J.E.2017bMethadone and corrected QT prolongation in pain and palliative care patients: a case-control studyJournal of Palliative Medicine(online early: doi: 10.1089/jpm.2016.0411not published, 28 Feb 17ADULT Adverse ADVERSE EFFECTS Age analysis CARDIOTOXICITY case-control case-control study DISEASE dose evidence FAILURE FEMALE Gender HEART heart failure history hypocalcemia hypokalemia IS LIVER LIVER DISEASE maintenance MALE MANAGEMENT METHADONE Methadone maintenance Methadone maintenance therapy MODEL Odds Ratio OPIOID P pain Pain management Palliative care PATIENT PEPTIC ULCER QT QT prolongation QTc RISK Risk factor RISK FACTORS Risk stratification STUDY THERAPY torsades de pointes ULCER use WHO 2/10/2017BACKGROUND: Methadone (ME) is commonly used in pain and palliative care (PPC) patients with refractory pain or intolerable opioid adverse effects (AEs). A unique ME AE is its corrected QT (QTc) interval prolongation risk, but most evidence exists in methadone maintenance therapy patients. OBJECTIVE: Our goal was to identify QTc interval prolongation risk factors in PPC patients receiving ME and other medications known to prolong the QTc interval and develop a risk stratification tool. DESIGN: We performed a case-control study of adult inpatients receiving ME for pain management. Settings/Subjects: Adult inpatients receiving ME with a QTc >470 msec (males) and >480 msec (females) were matched 1:2 according to age, history of QTc prolongation, and gender with ME patients who did not have a prolonged QTc interval. QTc prolongation risk factors were collected for both groups. Covariates were analyzed using conditional logistic regression. Classification and regression tree analysis was used to identify the ME dose associated with QTc prolongation. RESULTS: Predictors of QTc prolongation included congestive heart failure (CHF) (OR: 11.9; 95% CI: 3.7-38.2; p < 0.00), peptic ulcer disease (PUD) (odds ratio [OR]: 8.3; 95% confidence interval [95% CI]: 2.4-28.9; p < 0.00), hypokalemia (OR: 6.5; 95% CI: 1.5-28.2; p < 0.01), rheumatologic diseases (OR: 4.7; 95% CI: 1.6-13.9; p < 0.00), taking medications with a known torsades de pointes (TdP) risk (OR: 4.4; 95% CI: 1.8-10.7; p < 0.01), malignancy (OR: 3.3; 95% CI: 1.2-9.3; p < 0.03), hypocalcemia (OR: 2.1; 95% CI: 0.9-4.8; p < 0.07), and ME doses >45 mg per day (OR: 1.9; 95% CI: 0.8-4.8; p < 0.16). Mild liver disease was protective against QTc prolongation (OR: 0.05; 95% CI: 0.0-0.46; p < 0.01). CONCLUSIONS: Predictors of QTc prolongation in our multivariate conditional logistic regression model included CHF, PUD, hypokalemia, rheumatologic disorders, use of medications with a known TdP risk, malignancy, hypocalcemia, and ME doses >45 mg per day120903' field[33]: Not in File B?AJuhasz, A. Pap, D. Barta, I. Drozdovszky, O. Egresi, A. Antus, B.2017TKinetics of exhaled carbon monoxide following waterpipe smoking indoors and early: doi: 10.1016/j.chest.2017.02.006not published, 01 Mar 17#Adverse As carbon CARBON MONOXIDE CIGARETTE Cigarette smokers Cohort Cotinine Environment evidence EXPOSURE HAZARD HEALTH Health effects Health hazard health hazards INDOOR IS KINETICS LEVELS method methods PASSIVE SMOKE SMOKING STUDY TOBACCO Tobacco smoking Toxicant urinary waterpipe youth 2/16/2017BACKGROUND: Despite accumulating evidence about its adverse health effects, waterpipe tobacco smoking has become very popular among youth. The aim of this study was to compare smoke exposure and the kinetics of exhaled carbon monoxide (eCO) between waterpipe and cigarette smokers under different conditions. METHODS: Using a cross-over study design, changes in eCO and urinary cotinine levels were measured in a cohort of 32 healthy university students following sessions of waterpipe smoking indoor and outdoor. An indoor cigarette smoking session with equal amounts of tobacco was conducted for reference purposes. Both active and passive smokers participated in all sessions. RESULTS: In indoor sessions we found that among active participants eCO levels were approximately 7.5-fold higher in waterpipe users compared to cigarette smokers. eCO levels remained significantly elevated even 10 hours after discontinuing waterpipe smoking. Notably, eCO levels in passive waterpipe smokers were in the same range as in active cigarette smokers. Compared to indoor sessions, eCO levels in active waterpipe users were reduced in outdoor environments. Nonetheless, levels were still higher in these subjects compared to those in active cigarette smokers measured in indoor sessions. Urinary cotinine levels were comparable in active waterpipe and cigarette smokers. CONCLUSIONS: Our results suggest that waterpipe smoking is associated with significantly higher toxicant exposure than cigarette smoking even in outdoor environment. Furthermore, even passive, indoor waterpipe smoke exposure may have significant health hazards compared to those of active cigarette smoking120968- field[33]: Not in Filef?!Juntarawijit, C. Juntarawijit, Y.2017HCooking smoke and respiratory symptoms of restaurant workers in Thailand41BMC Pulmonary Medicine171wAs Attention Biomass CHRONIC COMPARISON Cough DATA DOE Dyspnea EXPOSURE FOOD Frequency FUMES HEALTH HOME INHALATION IS men method methods OCCUPATIONAL Occurrence OIL P prevalence PUBLIC QUESTIONNAIRE RESEARCH RESPIRATORY RESPIRATORY SYMPTOMS RISK Risk factor RISK FACTORS SAFETY SMOKE SURVEY susceptibility SYMPTOMS Thailand Time toxic VENTILATION WHO WOMEN workers workplace 2/17/2017 BACKGROUND: Restaurant workers are at risk from exposure to toxic compounds from burning of fuel and fumes from cooking. However, the literature is almost silent on the issue. What discussion that can be found in the literature focuses on the potential effects from biomass smoke exposure in the home kitchen, and does not address the problem as occurring in the workplace, particularly in restaurants. METHODS: This was a cross-sectional survey of 224 worker from 142 food restaurants in the Tha Pho sub-district of Phitsanulok, a province in Thailand. The standard questionnaire from the British Medical Research Council was used to collect data on chronic respiratory symptoms, including cough, phlegm, dyspnea, severe dyspnea, stuffy nose in the participating workers. Data on their health symptoms experienced in the past 30 days was also asked. A constructed questionnaire was used to collect exposure data, including type of job, time in the kitchen, the frequency of frying food, tears while cooking (TWC), the type of restaurant, fuel used for cooking, the size and location of the kitchen, and the exhaust system and ventilation. The prevalence of the symptoms was compared with those obtained from 395 controls, who were neighbors of the participants who do not work in a restaurant. RESULTS: In comparison to the control group, the restaurant workers had twice or more the prevalence on most of the chronic health symptoms. Men had a higher risk for "dyspnea", "stuffy nose" and "wheeze" while women had higher risk of "cough". A Rate Ratio (RR) of susceptibility was established, which ranged from 1.4 up to 9.9. The minimum RR was for women with "severe dyspnea" (RR of 1.4, 95%CI 0.8, 2.5) while the men showed the maximum RR of 9.9 (95%CI 4.5-22.0) for "wheeze". Possible risk factors identified were job description, job period, size of restaurant, kitchen location, type of cooking oil, hours of stay in the kitchen area, number of fry dishes prepared, frequency of occurrence of TWC, and additional cooking at home. Working for 6-10 year increased the risk of "cough" with an Odd Ratio (OR) of 3.19 (P < 0.01) while working for more than 10 years increased the risk of "cough" (OR = 3.27, P < 0.01), "phlegm" (OR = 3.87, P = 0.01) and "wheeze" (OR = 2.38, P = 0.05). Working as a chef had a higher risk of "cough" by 2.33 (P = 0.01) as comparing to other jobs. Workers in a relatively large restaurant using 4 or more stoves had increased risk of "wheeze" with OR of 3.81 (P < 0.01) and "stuffy nose" with OR of 3.56 (P < 0.01). Using vegetable oil increased the risk of "stuffy nose" by 2.94 (P < 0.01). Every 10 h of stay in the kitchen area was associated with a minimal increase in the risk of "cough", "wheeze" and "symptoms in the past 30 days" by 1.15 (P = 0.02), 1.16 (P = 0.01) and 1.16 (P = 0.02), respectively. CONCLUSIONS: Restaurant workers are at risk of respiratory symptoms caused by exposure to toxic compounds from cooking fumes. Job description, job period, size of restaurant, kitchen location, type of cooking oil, hours of stay in the kitchen area, number of fry dishes prepared, frequency of occurrence of TWC, and additional cooking at home were the predictive factors. Workplace Health and Safety protection of restaurant worker is urgently needed and the issue should receive more public attention120952+ field[33]: Not in File B?Kairo, G. Poquet, Y. Haji, H. Tchamitchian, S. Cousin, M. Bonnet, M. Pelissier, M. Kretzschmar, A. Belzunces, L.P. Brunet, J.-L.2017Assessment of the toxicity of pesticides on honey bee drone fertility using laboratory and semi-field approaches: a case study of fipronil&Environmental Toxicology and Chemistry#online early: doi: 10.1002/etc.3773not published, 01 Mar 174Affect ASSESSMENT bee Bees case case studies Case Study ENVIRONMENTAL FERTILITY FIPRONIL HONEY impact IMPAIRMENT IS Laboratories LABORATORY method methods MORTALITY pesticide PESTICIDES PLANT reproductive toxicity RISK RISK ASSESSMENT SEMEN seminal fluid SPERMATOZOA STUDY SURVIVAL Toxicities TOXICITY Volume 2/22/2017)Concern about the reproductive toxicity of plant protection products (PPPs) in honey bee reproducers is increasing. Because the reproductive capacity of honey bees is not currently considered during the risk assessment procedures performed during PPP registration, it is important to provide methods to assess such potential impairments. To achieve this aim, we used two different approaches that involved semi-field (SF) and laboratory (Lab) conditions to study the impact of Fipronil on drone fertility. For each approach, the drones were reared for 20 days, from emergence to sexual maturity, and exposed to Fipronil via a contaminated sugar solution. In both groups, the effects of Fipronil were determined by studying life traits and fertility indicators. The results showed that the survival and maturity rates of the drones were better under Lab conditions than under SF conditions. Moreover, the drones reared under Lab conditions produced more seminal fluid. While these differences could be explained by environmental factors that may vary under SF conditions, we found that regardless of the approach that was used, Fipronil did not affect survival rates, maturity rates or semen volumes, whereas it did affect fertility by inducing a decrease in spermatozoa quantity that was associated with an increase in spermatozoa mortality. These results confirm that Fipronil affects drone fertility and support the relevance of each approach for assessing the potential reproductive toxicity of PPPs in honey bees. This article is protected by copyright. All rights reserved120990" field[33]: Not in File?CKaraman, A. Omeroglu, M. Emet, M. Kerget, B. Subasi, I.D. Alper, F.2016CLenalidomide induced late-onset acute respiratory distress syndrome228-229Eurasian Journal of Medicine483ACUTE ADULT ADULT RESPIRATORY DISTRESS SYNDROME BREATH CHRONIC DISEASE EMBOLISM Emergencies emergency EMERGENCY DEPARTMENT history LATE LUNG Man multiple myeloma MYELOMA Obstructive PULMONARY pulmonary embolism RESPIRATORY respiratory distress Syndrome10/2016A 77-year-old man with multiple myeloma (MM) presented with shortness of breath to the emergency department. He also had history of chronic obstructive pulmonary disease, chronic pulmonary embolism and nephrectomy due to malignancy 10 years ago. He had been treated for 9 months with lenalidomide because of MM. He diagnosed with adult respiratory distress syndrome due to lenalidomide. We aimed to demonstrate late onset and destructive effects of lenalidomide on the lungs1207440 field[33]: Not in File??Kavaliauskiene, S. Dyve Lingelem, A.B. Skotland, T. Sandvig, K.2017Protection against Shiga toxins44Toxins (Basel)92^ANIMAL Animals apoptosis CELL HUMAN Humans INTERACTION IS PROTEIN Synthesis toxic toxin TOXINS2/3/2017~Shiga toxins consist of an A-moiety and five B-moieties able to bind the neutral glycosphingolipid globotriaosylceramide (Gb3) on the cell surface. To intoxicate cells efficiently, the toxin A-moiety has to be cleaved by furin and transported retrogradely to the Golgi apparatus and to the endoplasmic reticulum. The enzymatically active part of the A-moiety is then translocated to the cytosol, where it inhibits protein synthesis and in some cell types induces apoptosis. Protection of cells can be provided either by inhibiting binding of the toxin to cells or by interfering with any of the subsequent steps required for its toxic effect. In this article we provide a brief overview of the interaction of Shiga toxins with cells, describe some compounds and conditions found to protect cells against Shiga toxins, and discuss whether they might also provide protection in animals and humans120925' field[33]: Not in File?JKaye, A.D. Jones, M.R. Kaye, A.M. Ripoll, J.G. Jones, D.E. Galan, V. Beakley, B.D. Calixto, F. Bolden, J.L. Urman, R.D. Manchikanti, L.2017Prescription opioid abuse in chronic pain: an updated review of opioid abuse predictors and strategies to curb opioid abuse (part 2) S111-S133Pain Physician202S-ABUSE ACCIDENTAL ADDICTION As ASSESSMENT author Behavior behaviors CHRONIC chronic pain CLINICAL comorbid DISEASE DRUG Drug testing Guidelines HEALTH IATROGENIC IS MANAGEMENT Mental health method MISUSE MONITORING MORBIDITY MORTALITY NO Occurrence OPIOID Opioid abuse Opioid overdose Opioid Treatment Opioids OVERDOSE pain PATIENT prevalence PREVENTION REVIEW RISK RISK ASSESSMENT Risk factor RISK FACTORS RISK MANAGEMENT SCREENING Self Medication SUBSTANCE ABUSE Substance use SURVEILLANCE TEST Testing THERAPEUTIC THERAPY TREATMENT UNITED STATES URINE use2/2017 Chronic pain and prescription opioid abuse are extremely prevalent in the United States and worldwide. The consequences of opioid misuse can be life-threatening with significant morbidity and mortality, exacting a heavy toll on patients, physicians, and society. The risk for misuse of prescribed opioids is much higher in patients with chronic pain, especially those with concurrent substance use and /or mental health disorders. Several reasons can account for the occurrence of opioid abuse and misuse, including self-medication, use for reward, compulsive use related to addiction, and diversion for profit. There is a need, therefore, for therapeutic approaches that balance treating chronic pain, while minimizing risks for opioid abuse, misuse, and diversion. Chronic opioid therapy for chronic non-cancer pain has seen a dramatic increase throughout the past 2 decades in conjunction with associated increases in the abuse of prescribed opioids and accidental opioid overdoses. Consequently, a validated screening instrument that provides an effective and rational method for selecting patients for opioid therapy, predicting risk, and identifying problems once they have arisen, could be of enormous benefit in clinical practice. An instrument as such has the potential to attenuate the risk of iatrogenic addiction. Despite the recent introduction of various screening strategies and instruments, no single test or instrument can reliably and accurately predict those patients unsuitable for opioid therapy or pinpoint those requiring heightened degrees of surveillance and monitoring throughout their therapy. Current opioid abuse screening tactics include assessing premorbid and comorbid substance abuse; assessing aberrant drug-related behaviors; stratification of risk factors; and utilizing opioid assessment screening tools. Several authors have contributed numerous screening tools and instruments to aid the assessment of appropriate opioid therapy. Additional essential measures include urine drug testing, prescription practice monitoring programs, opioid treatment agreements, and implementing universal precautions. Presently accepted recommendations consist of a combination of strategies designed to stratify risk, to identify and to understand aberrant drug-related behaviors, and to tailor treatments accordingly. This manuscript, Part 2 of a 2 part update, builds on the 2012 opioid guidelines published in Pain Physician, and the 2016 guidelines released by the Centers for Disease Control and Prevention. It reviews screening, monitoring, and addressing opioid abuse and misuse in patients with chronic non-cancer pain. Opioids, misuse, abuse, chronic pain, prevalence, risk assessment, risk management, drug monitoring, aberrant drug-related behavior121086K Not in FileF?J{Kaye, A.D. Jones, M.R. Kaye, A.M. Ripoll, J.G. Galan, V. Beakley, B.D. Calixto, F. Bolden, J.L. Urman, R.D. Manchikanti, L.2017Prescription opioid abuse in chronic pain: an updated review of opioid abuse predictors and strategies to curb opioid abuse: part 1S93-S109Pain Physician202SIABUSE ACCIDENTAL ADDICTION ASSESSMENT author Behavior behaviors CHRONIC chronic pain CLINICAL comorbid DISEASE DRUG Drug testing Guidelines HEALTH IATROGENIC IS Knowledge MANAGEMENT Mental health method methods MISUSE MONITORING MORBIDITY MORTALITY NO OPIOID Opioid abuse Opioid overdose Opioid Treatment Opioids OVERDOSE pain PATIENT PRESCRIBING prevalence PREVENTION REVIEW RISK RISK ASSESSMENT Risk factor RISK FACTORS RISK MANAGEMENT SCREENING Self Medication SUBSTANCE ABUSE Substance use substance use disorder Substance use disorders TEST Testing THERAPY TREATMENT URINE use WHO2/2017 Chronic pain and prescription opioid abuse are extremely prevalent both in this country and worldwide. Consequences of opioid misuse can be life-threatening with significant morbidity and mortality, exacting a heavy toll on patients, physicians, and society. Individuals with chronic pain and co-occurring substance use disorders and/or mental health disorders, are at a higher risk for misuse of prescribed opioids. Opioid abuse and misuse occurs for a variety of reasons, including self-medication, use for reward, compulsive use because of addiction, and diversion for profit. There is a significant need for treatment approaches that balance treating chronic pain; while minimizing risks for opioid abuse, misuse, and diversion. The use of chronic opioid therapy for chronic non-cancer pain has increased dramatically in the past 2 decades in conjunction with associated increases in the abuse of prescribed opioids and accidental opioid overdoses. Consequently, a validated screening instrument which provides an effective and rational method of selecting patients for opioid therapy, predicting risk, and identifying problems once they arise could be of enormous benefit in clinical practice. Such an instrument could potentially curb the risk of iatrogenic addiction. Although several screening instruments and strategies have been introduced in recent years, there is no single test or instrument which can reliably and accurately predict those patients not suitable for opioid therapy or identify those who need increased vigilance or monitoring during therapy. At present, screening for opioid abuse includes assessment of premorbid and comorbid substance abuse; assessment of aberrant drug-related behaviors; risk factor stratification; and utilization of opioid assessment screening tools. Multiple opioid assessment screening tools and instruments have been developed by various authors. In addition, urine drug testing, monitoring of prescribing practices, prescription monitoring programs, opioid treatment agreements, and utilization of universal precautions are essential. Presently, a combination of strategies is recommended to stratify risk, to identify and understand aberrant drug related behaviors, and to tailor treatments accordingly. This manuscript builds on the 2012 opioid guidelines published in Pain Physician and the 2016 guidelines released by the Centers for Disease Control and Prevention. It reviews the current state of knowledge regarding the growing problem of opioid abuse and misuse; known risk factors; and methods of predicting, assessing, monitoring, and addressing opioid abuse and misuse in patients with chronic non-cancer pain.Key words: Opioids, misuse, abuse, chronic pain, prevalence, risk assessment, risk management, drug monitoring, aberrant drug-related behavior121085J Not in File?,Keil, A.P. Daniels, J.L. Hertz-Picciotto, I.2014Autism spectrum disorder, flea and tick medication, and adjustments for exposure misclassification: the CHARGE (childhood autism risks from genetics and environment) case-control study1-10Environmental Health133=analysis Association AUTISM case case-control study childhood CHILDREN Environment ENVIRONMENTAL EXPOSURE genetic GENETICS HOUSEHOLD IMIDACLOPRID INFORMATION MODEL NEONICOTINOID neonicotinoids pesticide PESTICIDES PET PREGNANCY PRENATAL Prenatal exposure RISK Sensitivity STUDY susceptibility TREATMENT use Validation2014The environmental contribution to autism spectrum disorders (ASD) is largely unknown, but household pesticides are receiving increased attention. We examined associations between ASD and maternally-reported use of imidacloprid, a common flea and tick treatment for pets. Bayesian logistic models were used to estimate the association between ASD and imidacloprid and to correct for potential differential exposure misclassification due to recall in a case control study of ASD. Our analytic dataset included complete information for 262 typically developing controls and 407 children with ASD. Compared with exposure among controls, the odds of prenatal imidacloprid exposure among children with ASD were slightly higher, with an odds ratio (OR) of 1.3 (95% Credible Interval [CrI] 0.78, 2.2). A susceptibility window analysis yielded higher ORs for exposures during pregnancy than for early life exposures, whereas limiting to frequent users of imidacloprid, the OR increased to 2.0 (95% CI 1.0, 3.9). Within plausible estimates of sensitivity and specificity, the association could result from exposure misclassification alone. The association between imidacloprid exposure and ASD warrants further investigation, and this work highlights the need for validation studies regarding prenatal exposures in ASD.120815( field[33]: Not in File B?5Kelly, J.F. Fallah-Sohy, N. Cristello, J. Bergman, B.2017Coping with the enduring unpredictability of opioid addiction: an investigation of a novel family-focused peer-support organization$Journal of Substance Abuse Treatment-online early: doi: 10.1016/j.jsat.2017.02.010not published, 01 Mar 17 ADDICTION ADULT Benefits CHILDREN CLINICAL DEATH Deaths DISTRIBUTION family HEALTH history INFORMATION IS MALE method Middle Aged MOTHERS OPIOID opioid addiction Opioid overdose Opioids OVERDOSE PUBLIC PUBLIC HEALTH Qualitative Reduction Source STRESS SURVEY Time WHO 2/17/2017BACKGROUND: Opioid overdose deaths have become a major public health crisis. While efforts have focused mostly on helping opioid-addicted individuals directly, family members suffer also from the grave and enduring unpredictability associated with opioid addiction and often play a vital role in helping addicted loved ones access care. Little is known, however, about resources to help affected family members. Here we describe results from the first quantitative and qualitative investigation of a free and growing support organization for family members of addicted individuals ("Learn to Cope" [LTC];, organized around three key questions: 1. Who participates, how often, and in what ways? 2. What are the demographic and clinical histories of their addicted loved-ones? 3. How do participants benefit? METHOD: Survey with LTC members at meetings and online (N=509; 95% participation rate). RESULTS: 1. Participants were primarily middle-aged mothers (77%) of opioid-addicted adult male children, attending LTC meetings several times per month, using LTC online resources several times a week, and meeting with LTC members between meetings. 2. Their addicted loved-ones were mostly male (73%), addicted to opioids (88%), with a criminal history (70%), with just under half (41%) having suffered at least one prior overdose. Almost three-quarters (71%), however, reported their loved one was "in recovery", with 30% having a year or more. 3. Benefits since beginning participation included gains in understanding and coping with addiction, feeling better able to help and communicate with their loved-one, and reductions in self-blame and stress. Of members trained in Narcan administration (66%), 86% had received training at LTC meetings; LTC members reported having deployed Narcan for over 44 overdose reversals. CONCLUSION: The growing availability of LTC may provide a needed source of support and information for family members of opioid-addicted loved-ones and may help reduce overdose deaths through Narcan training and distribution121063, field[33]: Not in File B?0Kennedy, D. Webster, W.S. Hill, M. Ritchie, H.E.2017xAbnormal pregnancy outcome associated with high-dose maternal tranylcypromine therapy: case report and literature reviewReproductive Toxicology1online early: doi: 10.1016/j.reprotox.2017.02.012not published, 01 Mar 17lALPRAZOLAM As AUTOPSY BLOOD CARDIAC case CASE REPORT Case-report CHILDREN DEATH DEPRESSION DEVELOPMENTAL DIAZEPAM dose DRUG drugs EXPOSURE FETAL FOOD HYPOXIA INFORMATION INTERACTION IS LITERATURE REVIEW Malformations MAO NOREPINEPHRINE OCULAR outcome PATIENT PIMOZIDE PREGNANCY Pregnancy outcome REACTIONS Reduction REVIEW SERVICE SHEEP THERAPY TRANYLCYPROMINE use 2/22/2017BACKGROUND: Tranylcypromine is a non-selective inhibitor of monamine oxidase which also inhibits the reuptake of norepinephrine. Spontaneous hypertensive reactions to the drug have been reported. In sheep tranylcypromine has been shown to cause a dose-dependent reduction in uterine blood flow. A similar effect in a pregnant woman might induce constriction of the uterine arteries and temporary fetal hypoxia. CASES: MotherSafe is a state-based Teratogen Information service and currently provides counselling to around 22,000 consumers and healthcare professionals annually regarding exposures during pregnancy and breastfeeding We report on the outcome of 2 pregnancies in a patient treated with high dose tranylcypromine as well as pimozide, diazepam and alprazolam. The first pregnancy resulted in fetal death and autopsy revealed facial dysmorphism with ocular hypertelorism, cardiac defect and placental infarcts. The second pregnancy continued to term but the baby had similar dysmorphic features as well as an atrio-ventricular septal defect and craniosynostosis. CONCLUSIONS: Due to their unpredictable interactions with many drugs and foods, MAO inhibitors such as tranylcypromine are not commonly used to treat depression and reports of use in pregnancy are rare. We report the outcome of 2 pregnancies with exposure to high doses of tranylcypromine resulting in children with a similar pattern of malformations. The aetiology is unknown but may relate to the vasoactive properties of the drug in above-therapeutic doses1211070 field[33]: Not in File;?Keough, L. Fantasia, H.C.2017<Pharmacologic treatment of opioid addiction during pregnancy34-44Nursing for Women's Health211<ACUTE acute poisoning ADDICTION Benefits BUPRENORPHINE DRUG evidence FETAL HEALTH IS LEAD medication assisted treatment medication-assisted treatment METHADONE MONITORING neonate NEONATES OPIOID opioid addiction Opioids outcome POISONING PREGNANCY RISK SYMPTOMS TREATMENT use WHO WITHDRAWAL Withdrawal symptoms WOMEN2/20173Opioid addiction during pregnancy presents a treatment challenge to clinicians and women alike. Untreated addiction can lead to poor maternal and fetal health outcomes. Medication-assisted treatment is the standard of care, and methadone is the current drug of choice for treatment. Emerging evidence also supports the use of buprenorphine during pregnancy. Both methadone and buprenorphine have risks and benefits that should be explored before initiating treatment. Clinicians who work in obstetrics and in addiction treatment can collaborate and coordinate treatment to ensure optimal maternal and fetal outcomes. Women undergoing treatment will require frequent monitoring, particularly in the third trimester. Neonates born to women receiving treatment may have withdrawal symptoms and require additional treatment120913+ field[33]: Not in File v?:Khadrawy, Y.A. Sawie, H.G. Abdel-Salam, O.M.E. Hosny, E.N.2017JCannabis exacerbates depressive symptoms in rat model induced by reserpine41-50Behavioural Brain Research324ACETYLCHOLINESTERASE As BRAIN CANNABIS DEPRESSION DRUG drugs Hippocampus IMPAIRMENT IS LEVELS LIPID LIPID PEROXIDATION MEMORY MODEL motor NITRIC OXIDE NO OXIDATIVE STRESS PATIENT PEROXIDATION RAT rats RECREATIONAL DRUGS STRESS STUDY SYMPTOMS TEST use 2/14/2017Cannabis sativa is one of the most widely recreational drugs and its use is more prevalent among depressed patients. Some studies reported that Cannabis has antidepressant effects while others showed increased depressive symptoms in Cannabis users. Therefore, the present study aims to investigate the effect of Cannabis extract on the depressive-like rats. Twenty four rats were divided into: control, rat model of depression induced by reserpine and depressive-like rats treated with Cannabis sativa extract (10mg/kg expressed as Delta9-tetrahydrocannabinol). The depressive-like rats showed a severe decrease in motor activity as assessed by open field test (OFT). This was accompanied by a decrease in monoamine levels and a significant increase in acetylcholinesterase activity in the cortex and hippocampus. Na+,K+-ATPase activity increased in the cortex and decreased in the hippocampus of rat model. In addition, a state of oxidative stress was evident in the two brain regions. This was indicated from the significant increase in the levels of lipid peroxidation and nitric oxide. No signs of improvement were observed in the behavioral and neurochemical analyses in the depressive-like rats treated with Cannabis extract. Furthermore, Cannabis extract exacerbated the lipid peroxidation in the cortex and hippocampus. According to the present findings, it could be concluded that Cannabis sativa aggravates the motor deficits and neurochemical changes induced in the cortex and hippocampus of rat model of depression. Therefore, the obtained results could explain the reported increase in the depressive symptoms and memory impairment among Cannabis users120949+ field[33]: Not in FileO?Khlystov, A. Samburova, V.2017iResponse to comment on "Flavoring compounds dominate toxic aldehyde production during e cigarette vaping" 2493-2494"Environmental Science & Technology514[ALDEHYDES CIGARETTE E CIGARETTE E Cigarettes E-CIGARETTE e-Cigarettes e-liquid LETTER toxic2/7/2017120877) field[33]: Not in FileB?/Kilic, S. Özkaya, E. Baykal, C. Vatansever, S.2017ZVemurafenib-induced toxic epidermal necrolysis: is it an emerging side effect of the drug?<Journal of the European Academy of Dermatology & Venereology$online early: doi: 10.1111/jdv.14150not published, 16 Feb 17Adverse adverse reactions adverse skin reaction ANTINEOPLASTIC DRUGS As case CLINICAL CUTANEOUS DERMAL DRUG drugs IS LESIONS Maculopapular rash PATIENT RASH REACTIONS Side effect SKIN toxic TREATMENT2/1/2017Vemurafenib, a selective inhibitor of the BRAF-kinase used in treatment of metastatic melanoma alone or in combinations,1 is known to cause various adverse skin reactions such as maculopapular rash, photosensitivity and hyperkeratotic lesions, affecting more than 90% of patients.1-2 Severe adverse reactions were observed in less than 1% of the patients in clinical trials.3 However, the increasing number of reported cases of vemurafenib-induced toxic epidermal necrolysis (TEN), a life-threatening severe cutaneous adverse reaction, is striking. 4-8 We herein present another patient with vemurafenib-induced TEN. This article is protected by copyright. All rights reserved120741# field[33]: Not in File?\Kiljanek, T. Niewiadowska, A. Gawel, M. Semeniuk, S. Borzecka, M. Posyniak, A. Pohorecka, K.2017^Multiple pesticide residues in live and poisoned honeybees – Preliminary exposure assessment36-44 Chemosphere175KACUTE AMITRAZ As ASSESSMENT CHLORPYRIFOS clothianidin DATA DIMETHOATE DMF dose EXPOSURE EXPOSURE ASSESSMENT FUNGICIDE Fungicides GC-MS/MS HAZARD HEALTH impact interpretation LC-MS/MS lethal METABOLITE Metabolites pesticide Pesticide residues PESTICIDES PLANT POISONING RESIDUE Residues STUDY SYSTEMIC toxic toxic effects Veterinary2/8/2017qStudy combines data about the exposure of honeybees to pesticides from plant protection products and veterinary medicinal products. Residues of 200 pesticide and pesticide metabolites in 343 live and 74 poisoned honeybee samples, obtained during the years of 2014-2015, were determined by LC-MS/MS and GC-MS/MS. In 44% of live honeybee 48 different pesticide residues were found, mainly amitraz metabolites (DMF, DMPF) and chlorpyrifos. In 98% of poisoned honeybee 57 pesticides and metabolites were detected, mainly chlorpyrifos, dimethoate and clothianidin. In total 84 different pesticides were detected both in live and poisoned honeybees, they indicate 30 various modes of action. Differences between mean number of pesticide residues detected in live and poisoned honeybees clearly indicate the impact of multiple pesticides on honeybee health. Possible impact of systemic fungicides on the health of honeybees was studied. Applicability of hazard quotient counted as ratio between concentration of pesticides in honeybees and lethal dose in the interpretation whether detected concentration indicates acute toxic effects was shown1209663 field[33]: Not in File? Kilmer, B.2017GRecreational cannabis — Minimizing the health risks from legalization705-707New England Journal of Medicine3768ADOLESCENT Adolescents ADULT Age Benefits CANNABIS cannabis legalization chemical cognitive Delta-9-tetrahydrocannabinol dependence evidence HEALTH Health risk Health risks INTOXICATION IS legalization PATIENT policy Population PUBLIC RESEARCH RISK STUDY SYMPTOMS THC THERAPEUTIC use WHO 2/17/2017120840& field[33]: Not in File?Kim, H. Ryu, J.2016'[Acute occupational poisoning in Korea]99-103EWHA Medical Journal394ACUTE As case CLINICAL ENVIRONMENTAL HAZARD HEALTH INFORMATION injuries Injury IS Korea Medicine OCCUPATIONAL PATIENT POISONING poisonings PUBLIC SAFETY SURVEILLANCE SURVEY WHO workers workplace20161Although acute occupational poisonings are very rare officially, it seems that there are a considerable number of unreported cases seen from non-intentional poisoning cases of the national injury and poisoning survey on discharged patients. Establishing a proper national surveillance system for acute occupational poisonings is needed. It is difficult for clinical physicians to diagnose acute occupational poisonings appropriately because the victims who usually are not mentally alert can not provide the information on the workplace hazard. Consulting a specialist of occupational and environmental medicine may help to reveal the cause of poisoning. Furthermore, reporting to the public organization such as workers health center and Korea occupational safety and health is helpful to prevent additional injuries120731+ field[22]: In Korean with English abstract RefMgr field[33]: Not in File eB?NKim, S.J. Kim, K.M. Yang, J.H. Cho, S.S. Lee, S.K. Ku, S.K. Cho, I.J. Ki, S.H.2017<Sestrin2 protects against acetaminophen-induced liver injuryChemico-Biological Interactions,online early: doi: 10.1016/j.cbi.2017.02.002not published, 01 Mar 17MACETAMINOPHEN ACUTE acute liver failure ADENOVIRUS ALANINE case CELL cytokine dose FAILURE GENE EXPRESSION GLUTATHIONE HEPATIC HEPATOTOXICITY INJECTION injuries Injury LEVELS LIVER Liver failure liver injury MICE MORTALITY OVERDOSE OXIDATIVE STRESS OXYGEN PARACETAMOL Pathway PROTEIN SERUM SPECIES STRESS STUDY TISSUE toxic TREATMENT 2/13/2017Acetaminophen (APAP) overdose accounts for half of the cases of acute liver failure worldwide. We previously reported that that Sestrin2 (Sesn2) protects against d-galactosamine/lipopolysaccharide-induced acute fulminant liver failure. In this study, we demonstrated that Sesn2 protects APAP-induced liver injury in mice, using a recombinant adenovirus encoding Sesn2 (Ad-Sesn2). First, we found that treatment of mice with toxic levels of APAP significantly reduced Sesn2 expression. Tail-vein injection with Ad-Sesn2 inhibited APAP-induced serum alanine aminotransferase and aspartate aminotransferase levels and markedly reduced hepatocyte degeneration and inflammatory cell infiltration. Additionally, APAP-induced glutathione depletion and reactive oxygen species generation was inhibited by Ad-Sesn2 treatment. Consistently, hepatic inflammatory gene expression and proinflammatory cytokine levels were also inhibited in Sesn2-infeced mice, and we observed reduced APAP-mediated apoptotic signaling by terminal transferase-mediated dUTP nick-end labeling staining of the hepatic tissue. At a high dose of APAP, the mortality rate of Ad-Sesn2-infected mice was significantly lower than that of control mice. Furthermore, Sesn2 prevented APAP-induced damage through suppression of downstream mitogen-activated protein kinase pathway activation. Therefore, Sesn2 exerted a protective effect against APAP-induced acute liver damage by inhibiting oxidative stress and proinflammatory signaling120960+ field[33]: Not in File B?Kitaguchi, T. Moriyama, Y. Taniguchi, T. Maeda, S. Ando, H. Uda, T. Otabe, K. Oguchi, M. Shimizu, S. Saito, H. Toratani, A. Asayama, M. Yamamoto, W. Matsumoto, E. Saji, D. Ohnaka, H. Miyamoto, N.2017CSAHi study: detection of drug-induced ion channel/receptor responses, QT prolongation, and arrhythmia using multi-electrode arrays in combination with human induced pluripotent stem cell-derived cardiomyocytes4Journal of Pharmacological and Toxicological early: doi: 10.1016/j.vascn.2017.02.001not published, 28 Feb 17sAMIODARONE ARRHYTHMIA ASSAY ASTEMIZOLE CARDIAC CARDIOTOXICITY CISAPRIDE CLINICAL DATA DETECTION DRUG Drug discovery drug effects drug-induced drugs duration FACILITIES FLUOXETINE guinea-pig HUMAN Incidence interpretation ION CHANNEL ISOPROTERENOL method methods MUSCLE OUABAIN PIG PIMOZIDE QT QT prolongation QUINIDINE Ranolazine STUDY Testing THIORIDAZINE use VANOXERINE2/2/20177INTRODUCTION: The use of multi-electrode arrays (MEA) in combination with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provides a promising method to predict comprehensive cardiotoxicity, including drug-induced QT prolongation and arrhythmia. We previously demonstrated that MEA in combination with hiPSC-CMs could provide a generalizable platform by using 7 reference drugs at 10 testing facilities. Using this approach, we evaluated responses to reference drugs that modulate a range of cardiac ion currents and have a range of arrhythmogenic effects. METHODS: We used the MEA system (MED64) and commercially available hiPSC-CMs (iCell cardiomyocytes) to evaluate drug effects on the beat rate, field potential duration (FPD), FPD corrected by Fridericia's formula (FPDc), and the incidence of arrhythmia-like waveforms. RESULTS: This assay detected the repolarization effects of Bay K8644, mibefradil, NS1643, levcromakalim, and ouabain; and the chronotropic effects of isoproterenol, ZD7288, and BaCl2. Chronotropy was also affected by K+ and Ca2+ current modulation. This system detected repolarization delays and the arrhythmogenic effects of quinidine, cisapride, thioridazine, astemizole, bepridil, and pimozide more sensitively than the established guinea pig papillary muscle action potential assay. It also predicted clinical QT prolongation by drugs with multiple ion channel effects (fluoxetine, amiodarone, tolterodine, vanoxerine, alfuzosin, and ranolazine). DISCUSSION: MEA in combination with hiPSC-CMs may provide a powerful method to detect various cardiac electrophysiological effects, QT prolongation, and arrhythmia during drug discovery. However, the data require careful interpretation to predict chronotropic effects and arrhythmogenic effects of candidate drugs with multiple ion channel effects120904- field[33]: Not in File?:Kivity, S. Zafrir, Y. Loebstein, R. Mouallem, M. Mayan, H.2016 Methotrexate toxicity - Response1199Autoimmunity Reviews1512'LETTER METHOTREXATE Toxicities TOXICITY2016120699. field[33]: Not in Filej?Klein, L. Bangh, S. Cole, J.B.2017_Intentional recreational abuse of quetiapine compared to other second-generation antipsychotics243-250%Western Journal of Emergency Medicine182ABUSE analysis Antipsychotic antipsychotics case CASE REPORT case reports Case-report CLINICAL DATA DATABASE IS method methods Poison QUETIAPINE STUDY SUBSTANCE ABUSE2/2017INTRODUCTION: Case reports and poison center data have demonstrated that the second-generation antipsychotic quetiapine is being obtained and used for recreational abuse. The purpose of this study was to describe the relative rates of single-substance abuse for different atypical antipsychotics and compare their demographic and clinical features. METHODS: We conducted a 10-year retrospective analysis of the National Poison Data System (NPDS) database (21211432 field[33]: Not in File ?Klingemann, J.2017rThe rights of drug treatment patients: experience of addiction treatment in Poland from a human rights perspective67-73$International Journal of Drug Policy43;ABUSE ACUTE acute poisoning ADDICTION As DATA dependence DOE DRUG DRUG ABUSE DRUG DEPENDENCE Drug testing Drug treatment FACILITIES FAILURE harm harm reduction HEALTH HUMAN ILLNESS INFORMATION IS method methods OPIOID PATIENT POISONING Reduction SERVICE SOCIAL SUBSTANCE ABUSE Testing THERAPEUTIC Time TREATMENT WHO 2/20/2017BACKGROUND: Drug dependence is a recognized medical condition and therefore, right to health applies in the same way to drug dependence as it does to any other health condition. The human rights in patient care framework - which refers to the application of basic human rights principles in the delivery of health care services - was used to explore the experiences of equality in the dignity and rights protected by Polish law within four different specialist drug treatment settings in Poland. The views of patients and staff were examined and compared. METHODS: Focus group interviews were conducted in 12 drug treatment facilities: three inpatient therapeutic communities, three outpatient programs, three opioid substitution programs and three harm reduction programs (drop-in/needle exchange/support). Interviews were conducted with a total of 43 staff and 73 patients. All interviews were audio-recorded with participants' prior consent and transcribed verbatim. Data were analysed according to the problem-centred interview methodology, using CAQDA. RESULTS: Patients described instances of abuse of their rights regarding dignity, privacy, confidentiality, personalized treatment, and respect of patient's time, right to information and to complain. Those accounts were complemented by the perspective of professionals working in drug treatment. Patients of Polish opioid substitution programs reported experiencing more humiliation and disenfranchisement than patients in other drug treatment settings. CONCLUSION: Drug testing and control, fuelled by prejudices of health professionals, are leading to discriminatory practices in substitution treatment and damaging the chances of therapeutic success. The concept of epistemic injustice illuminates the reasons behind discrimination against patients on opioid substitution programs, who are seen as continuously sick and their illness perceived as a mark of moral, social and epistemic failure121022. field[33]: Not in File ?J6Knezevic, N.N. Khan, O.M. Beiranvand, A. Candido, K.D.2017oRepeated quantitative urine toxicology analysis may improve chronic pain patient compliance with opioid therapy S135-S145Pain Physician202S Aged analgesic analysis As CHRONIC chronic pain CLINICAL COCAINE CONCENTRATIONS Consumption CREATININE DATA Decision making DRUG Drug testing drugs EDUCATION HEROIN Illicit drug Illicit drugs Laboratories LABORATORY LEVELS Liquid chromatography tandem mass spectrometry Liquid chromatography-tandem mass spectrometry MANAGEMENT MARIJUANA MASS SPECTROMETRY method methods MONITORING OPIOID OPIOID ANALGESIC Opioids pain Pain management PATIENT quality REVIEW SCREENING SPECTROMETRY STUDY Testing THERAPY TOXICOLOGY URINE urine toxicology use WHO2/2017 BACKGROUND: Even though serious efforts have been undertaken by different medical societies to reduce opioid use for treating chronic benign pain, many Americans continue to seek pain relief through opioid consumption. Assuring compliance of these patients may be a difficult aspect of proper management even with regular behavioral monitoring. OBJECTIVE: The purpose of this study was to accurately assess the compliance of chronic opioid-consuming patients in an outpatient setting and evaluate if utilizing repeated urine drug testing (UDT) could improve compliance. STUDY DESIGN: Retrospective analysis of prospectively collected data. SETTING: Outpatient pain management clinic. METHODS: After Institutional Review Board (IRB) approval, a retrospective analysis of data for 500 patients was conducted. We included patients who were aged 18 years and older who were treated with opioid analgesic medication for chronic pain. Patients were asked to provide supervised urine toxicology specimens during their regular clinic visits, and were asked to do so without prior notification. The specimens were sent to an external laboratory for quantitative testing using liquid chromatography-tandem mass spectrometry. RESULTS: Three hundred and eighty-six (77.2%) patients were compliant with prescribed medications and did not use any illicit drugs or undeclared medications. Forty-one (8.2%) patients tested positive for opioid medication(s) that were not prescribed in our clinic; 8 (1.6%) of the patients were positive for medication that was not prescribed by any physician and was not present in the Illinois Prescription Monitoring Program; 5 (1%) patients tested negative for prescribed opioids; and 60 (12%) patients were positive for illicit drugs (8.6% marijuana, 3.2% cocaine, 0.2% heroin). Repeated UDTs following education and disclosure, showed 49 of the 77 patients (63.6%) had improved compliance. LIMITATIONS: This was a single-site study and we normalized concentrations of opioids in urine with creatinine levels while specific gravity normalization was not used. CONCLUSIONS: Our results showed that repeated UDT can improve compliance of patients on opioid medications and can improve overall pain management. We believe UDT testing should be used as an important adjunctive tool to help guide clinical decision-making regarding opioid therapy, potentially increasing future quality of care.Key words: Urine toxicology analysis, chronic pain, opioids, compliance, pain management, urine drug testing, urine drug screening121082K Not in File ?yKo, J.-W. Shin, J.-Y. Kim, J.-W. Park, S.-H. Shin, N.-R. Lee, I.-C. Shin, I.-S. Moon, C. Kim, S.-H. Kim, S.-H. Kim, J.-C.2017}Protective effects of diallyl disulfide against acetaminophen-induced nephrotoxicity: A possible role of CYP2E1 and NF-kappaB156-165Food and Chemical Toxicology102LACETAMINOPHEN ANTIOXIDANT apoptosis As CATALASE CELL Content CYP2E1 GARLIC GLUTATHIONE Inhibition injuries Injury IS KIDNEY kidney injury LESIONS LIVER MECHANISM Mechanisms NECROSIS NEPHROTOXICITY OXIDATIVE STRESS PARACETAMOL PRETREATMENT RAT rats RENAL STRESS STUDY SUPEROXIDE SUPEROXIDE DISMUTASE tumor tumor necrosis factor-alpha 2/17/2017Diallyl disulfide (DADS) is a degradation product of allicin which is contained in garlic. This study investigated the protective effects of DADS against acetaminophen (AAP)-induced nephrotoxicity and the molecular mechanisms of nephroprotective effects in rats. AAP caused severe nephrotoxicity as evidenced by significant increases in renal tubular cell apoptosis, mitochondria-mediated apoptosis, and up-regulation of nuclear transcription factor kappa-B (NF-kappaB), cyclooxygenase-2 (Cox-2), and tumor necrosis factor-alpha (TNF-alpha) in the kidney with histopathological alterations. After AAP administration, glutathione content and activities of catalase, superoxide dismutase, and glutathione reductase were significantly decreased whereas malondialdehyde content was significantly increased, indicating that AAP-induced kidney injury was mediated through oxidative stress. In contrast, DADS pretreatment significantly attenuated AAP-induced nephrotoxic effects, including oxidative damage, histopathological lesions, and apoptotic changes in the kidney. DADS also attenuated AAP-induced up-regulation of NF-kappaB, Cox-2, and TNF-alpha in the kidney, and microsomal CYP2E1 expression in liver and kidney. These results indicated that DADS could prevent AAP-induced nephrotoxicity. The protective effects of DADS might be due to its ability to decrease metabolic activation of AAP by inhibiting CYP2E1 and its potent antioxidant, antiapoptotic, and antiinflammatory effects via inhibition of NF-kappaB121010+ field[33]: Not in File ?JKobayashi, L. Green, T.C. Bowman, S.E. Ray, M.C. McKenzie, M.S. Rich, J.D.2017Patient simulation for assessment of layperson management of opioid overdose with intranasal naloxone in a recently released prisoner cohort22-27Simulation in Healthcare121As ASSESSMENT baseline Checklist Cohort DATA EXPERIMENTAL FOLLOW UP Follow-up harm INTERACTION INTRANASAL Knowledge MANAGEMENT method methods NALOXONE OPIOID Opioid overdose Opioids OVERDOSE PATIENT PREVENTION Release RESEARCH REVIEW SIMULATION STUDY Time WHO2/2017INTRODUCTION: Investigators applied simulation to an experimental program that educated, trained, and assessed at-risk, volunteering prisoners on opioid overdose (OD) prevention, recognition, and layperson management with intranasal (IN) naloxone. METHODS: Consenting inmates were assessed for OD-related experience and knowledge then exposed on-site to standardized didactics and educational DVD (without simulation). Subjects were provided with IN naloxone kits at time of release and scheduled for postrelease assessment. At follow-up, the subjects were evaluated for their performance of layperson opioid OD resuscitative skills during video-recorded simulations. Two investigators independently scored each subject's resuscitative actions with a 21-item checklist; post hoc video reviews were separately completed to adjudicate subjects' interactions for overall benefit or harm. RESULTS: One hundred three prisoners completed the baseline assessment and study intervention and then were prescribed IN naloxone kits. One-month follow-up and simulation data were available for 85 subjects (82.5% of trained recruits) who had been released and resided in the community. Subjects' simulation checklist median score was 12.0 (interquartile range, 11.0-15.0) of 21 total indicated actions. Forty-four participants (51.8%) correctly administered naloxone; 16 additional subjects (18.8%) suboptimally administered naloxone. Nonindicated actions, primarily chest compressions, were observed in 49.4% of simulations. Simulated resuscitative actions by 80 subjects (94.1%) were determined post hoc to be beneficial overall for patients overdosing on opioids. CONCLUSIONS: As part of an opioid OD prevention research program for at-risk inmates, investigators applied simulation to 1-month follow-up assessments of knowledge retention and skills acquisition in postrelease participants. Simulation supplemented traditional research tools for investigation of layperson OD management120730. field[33]: Not in FileB? Koch, G. Schropp, J. Pfister, M.2017[Facilitate treatment adjustment after overdosing: another step toward 21st-century medicine Journal of Clinical Pharmacology#online early: doi: 10.1002/jcph.852not published, 16 Feb 17ACCIDENTAL ACUTE acute poisoning ADOLESCENT Adolescents ADULT As CHILDREN CLINICAL CONCENTRATIONS dose DRUG ELIMINATION errors INFANT Infants INFORMATION IS LEVELS Medicine neonate NEONATES NO PATIENT POISONING RISK safe SIMULATION THERAPEUTIC Time toxic TREATMENT2/2/2017Overdosing occurs frequently because of prescription errors in neonates, infants, children, adolescents, and adults. Currently there is no quantitative approach that can be used by clinicians to adjust dosing so that toxic drug concentrations can be brought back to levels observed with safe and efficacious therapeutic doses. We present a mathematical solution that offers the time between last overdosing and next therapeutic dose to achieve therapeutic drug concentrations as soon as possible. To facilitate applications of this solution in clinical practice, a minimal amount of information has to be provided, and no simulations are necessary to compute the optimal waiting time. For educational purposes, we provide access to an online decision support tool for overdosing situations (Time to next Dose Calculator) that (1) computes the waiting time after accidental overdosing in patients with normal elimination and (2) computes the waiting time and adjusted reference dosing for patients with abnormal elimination. This user-friendly online tool will help clinicians to quickly adjust a dosing schedule in overdosing situations to mitigate risk for negative clinical consequences120743" field[33]: Not in File ?Komaki, K. Kusaba, T. Tanaka, M. Kado, H. Shiotsu, Y. Matsui, M. Shiozaki, A. Nakano, H. Ishikawa, T. Fujiwara, H. Konishi, H. Itoh, Y. Matoba, S. Tamagaki, K.2017WLower blood pressure and risk of cisplatin nephrotoxicity: a retrospective cohort study144 BMC Cancer171ADULT analysis ANTIHYPERTENSIVE As baseline BLOOD BLOOD PRESSURE CANCER CELL CHEMOTHERAPY CISPLATIN Cohort Cohort studies Cohort study CREATININE discontinuation Esophageal FOOD GASTRIC Head and neck cancer HOSPITAL Incidence Intake INTRAVENOUS MECHANISM Mechanisms method methods NEPHROTOXICITY NO Odds Ratio outcome P PATIENT Reduction Regression Analysis RENAL RISK SERUM STUDY Time Toxicities TOXICITY use WHO 2/20/2017,BACKGROUND: The pathophysiological mechanisms of cisplatin nephrotoxicity include the reduction of renal blood flow, as well as tubular epithelial cell toxicity. The objective of this study was to investigate the influence of lower blood pressure and decreased food intake on the incidence of cisplatin nephrotoxicity. METHODS: We conducted a retrospective cohort study at a university hospital between 2011 and 2012. We identified hospitalized adult patients with head and neck cancer, esophageal cancer, or gastric cancer, who received intravenous cisplatin administration. The primary outcome was the incidence of cisplatin nephrotoxicity defined as the increase in serum creatinine after cisplatin administration more than 1.5 times from baseline. RESULTS: The study participants included 182 patients, in whom we observed a total of 442 cycles of cisplatin chemotherapy. The incidence of cisplatin nephrotoxicity was observed in 41 of 182 cycles with initial administration. Multivariate logistic regression analysis showed that systolic blood pressure was independently associated with cisplatin nephrotoxicity (adjusted odds ratio 0.75, 95% confidence interval 0.57 to 0.95 for each 10 mmHg). The use of renin-angiotensin system (RAS) inhibitors was also associated with cisplatin nephrotoxicity (3.39, 1.30 to 8.93). Among quartiles of systolic blood pressure in all cycles of chemotherapy, the incidence of nephrotoxicity in the lower blood pressure group was significantly higher than that in the higher blood pressure group for patients taking non-solid food (P = 0.037), while there was no significant difference for patients taking solid food (P = 0.67). CONCLUSIONS: Lower blood pressure and the use of RAS inhibitors were associated with the incidence of cisplatin nephrotoxicity, and lower blood pressure had a greater influence on nephrotoxicity in patients who could not take solid food. Discontinuation of antihypertensive medication including RAS inhibitors before cisplatin chemotherapy should be considered, which may be beneficial for patients with lower blood pressure120950. field[33]: Not in File >B?Krapf, M. Kunzi, L. Allenbach, S. Bruns, E.A. Gavarini, I. El-Haddad, I. Slowik, J.G. Prévôt, A.S. Drinovec, L. Mocnik, G. Dümbgen, L. Salathe, M. Baumlin, N. Sioutas, C. Baltensperger, U. Dommen, J. Geiser, M.2017XWood combustion particles induce adverse effects to normal and diseased airway epithelia*Environmental Science: Processes & Impacts%online early: doi: 10.1039/C6EM00586Anot published, 01 Mar 17=ACUTE Acute toxicity Adverse ADVERSE EFFECTS Aerosol Age Aged Aging AIRWAY ASTHMA CELL cell death chemical DEATH DONOR dose Emissions EXPOSURE FIBROSIS HEALTH Health effects HUMAN INHALATION IS LUNG MODEL OXIDATIVE STRESS particulate Particulate matter REMOVAL RESIDENTIAL SMOKE Source STRESS Toxicities TOXICITY WOOD 2/27/2017!Residential wood burning is a major source of poorly characterized, deleterious particulate matter, whose composition and toxicity may vary with wood type, burning condition and photochemical age. The causative link between ambient wood particle constituents and observed adverse health effects is currently lacking. Here we investigate the relationship between chemical properties of primary and atmospherically aged wood combustion particles and acute toxicity in human airway epithelial cells. Emissions from a log wood burner were diluted and injected into a smog chamber for photochemical aging. After concentration-enrichment and removal of oxidizing gases, directly emitted and atmospherically aged particles were deposited on cell cultures at the air-liquid interface for 2 hours in an aerosol deposition chamber mimicking physiological conditions in lungs. Cell models were fully differentiated normal and diseased (cystic fibrosis and asthma) human bronchial epithelia (HBE) and the bronchial epithelial cell line BEAS-2B. Cell responses were assessed at 24 hours after aerosol exposure. Atmospherically relevant doses of wood combustion particles significantly increased cell death in all but the asthma cell model. Expression of oxidative stress markers increased in HBE from all donors. Increased cell death and inflammatory responses could not be assigned to a single chemical fraction of the particles. Exposure to primary and aged wood combustion particles caused adverse effects to airway epithelia, apparently induced by several interacting components120987$ field[33]: Not in File ~B?Krause, D. Plörer, D. Koller, G. Martin, G. Winter, C. Adam, R. Canolli, M. Al-Iassin, J. Musselmann, R. Walcher, S. Schäfer, F. Pogarell, O.2017OHigh concomitant misuse of fentanyl in subjects on opioid maintenance treatmentSubstance Use and Misuse0online early: doi: 10.1080/10826084.2016.1246571not published, 16 Feb 17&ABUSE Age analysis As Association CONCENTRATIONS Consumption DATA diamorphine DRUG FENTANYL Germany IS maintenance maintenance treatment METHADONE method methods MISUSE OPIOID OVERDOSE P PATIENT QUESTIONNAIRE RISK STATISTICS STUDY SUBSTANCE ABUSE TEST THERAPY TREATMENT URINE Urine analysis WHO2/3/2017BACKGROUND: Concomitant opioid misuse is an increasing problem in opioid maintenance treatment as it interferes with treatment success. OBJECTIVE: Therefore, the rates of concomitant fentanyl misuse in opioid maintained patients were investigated. METHODS: We conducted a cross-sectional study which consisted in collecting data via urine samples and questionnaires in Germany. Urine samples of patients on opioid maintenance treatment were gathered and fentanyl concentrations were measured from 2008 to 2012. An anonymous questionnaire provided data on the consumption of fentanyl as concomitant drug. Data were analyzed with descriptive statistics and group differences were calculated using the Chi-Square test. RESULTS: Among the total sample (urine probes of 960 patients), 6.8% opioid maintained patients had positive urine samples for fentanyl and 37.9% reported concomitant fentanyl misuse (401 of these patients filled out the questionnaire). A significant age-related association of concomitant fentanyl misuse was identified in the urine analyses (chi2 = 7.489; p = .024) and also in the questionnaire data (chi2 = 11.899, p = .003), indicating that young age increased the probability of fentanyl consumption. Patients receiving methadone had the highest rates of concomitant fentanyl misuse with 18.4% according to urine analysis. In addition, the results show that patients who are on diamorphine are significantly less likely to misuse fentanyl. CONCLUSIONS: Fentanyl is a frequently used concomitant drug. Especially young patients and patients taking methadone are at high risk. Because of the life-threatening consequences of fentanyl overdose, patients taking fentanyl should be intensively medically surveilled120739/ field[33]: Not in File B?^Krishnan-Sarin, S. Morean, M. Kong, G. Bold, K.W. Camenga, D.R. Cavallo, D.A. Simon, P. Wu, R.20173E-cigarettes and "dripping" among high-school youth Pediatrics)online early: doi: 10.1542/peds.2016-3224not published, 28 Feb 17VADOLESCENT Adolescents Behavior behaviors CIGARETTE Cigarettes E CIGARETTE E Cigarettes E-CIGARETTE e-Cigarettes e-liquid ELECTRONIC CIGARETTE Electronic cigarettes Electronic-cigarette EVALUATION Frequency MALE method methods NICOTINE Odds Ratio PAEDIATRIC prevalence School STUDY SURVEY taste TOBACCO Toxicities TOXICITY use vapor WHO youth2/6/2017vBACKGROUND: Electronic cigarettes (e-cigarettes) electrically heat and vaporize e-liquids to produce inhalable vapors. These devices are being used to inhale vapors produced by dripping e-liquids directly onto heated atomizers. The current study conducts the first evaluation of the prevalence rates and reasons for using e-cigarettes for dripping among high school students. METHODS: In the spring of 2015, students from 8 Connecticut high schools (n = 7045) completed anonymous surveys that examined tobacco use behaviors and perceptions. We assessed prevalence rates of ever using e-cigarettes for dripping, reasons for dripping, and predictors of dripping behaviors among those who reported ever use of e-cigarettes. RESULTS: Among 1080 ever e-cigarette users, 26.1% of students reported ever using e-cigarettes for dripping. Reasons for dripping included produced thicker clouds of vapor (63.5%), made flavors taste better (38.7%), produced a stronger throat hit (27.7%), curiosity (21.6%), and other (7.5%). Logistic regression analyses indicated that male adolescents (odds ratio [OR] = 1.64), whites (OR = 1.46), and those who had tried multiple tobacco products (OR = 1.34) and had greater past-month e-cigarette use frequency (OR = 1.07) were more likely to use dripping (Ps < .05). CONCLUSIONS: These findings indicate that a substantial portion ( approximately 1 in 4) of high school adolescents who had ever used e-cigarettes also report using the device for dripping. Future efforts must examine the progression and toxicity of the use of e-cigarettes for dripping among youth and educate them about the potential dangers of these behaviors120917( field[33]: Not in File ?#Krzyzak-Jankowicz, M. Jankowicz, R.2016:Metamizol i paracetamol - Leki podobne, ale nie takie same59-65Medycyna Paliatywna w Praktyce92ACETAMINOPHEN ACUTE Adverse adverse reactions AGRANULOCYTOSIS analgesic ANALGESICS As CANNABINOID CARDIOVASCULAR COAGULATION dose DRUG drugs ENVIRONMENTAL FAILURE Fever Hand HEART HEPATIC HYPERTENSION impact INFARCTION IS LEAD Long term Long-term MECHANISM mechanism of action METAMIZOLE Monotherapy OVERDOSE pain PARACETAMOL PATIENT PREGNANCY REACTIONS RECEPTORS RENAL RENAL FAILURE RISK safe SEROTONIN STUDY THERAPEUTIC THERAPY Time TREATMENT WOMEN2016Both metamizole and paracetamol (acetaminophen) are popular non-opioid analgesics and antipyretic drugs. The mechanism of action of paracetamol and metamizol is complex and has been under debate for long time. The most probably mechanism responsible for the analgesic effect of metamizole is achieved through both action of COX-1/-2 and the impact on the opioidergic and cannabinoid system. Beside the analgesic and antipyretic effect, it produces also a significant spasmolytic effect. The results of recent studies reveal that paracetamol is a preferential inhibitor of COX-2 isoenzyme, however, its effect depends to a great extent on the state of environmental oxidation/reduction. The analgesic effect of paracetamol is also due to the activation of canabinoid CB receptors and the 5-HT3 subtype of serotonin receptors. Metamizole is predominantly applied in the therapy of acute pain, especially visceral pain, and of fever refractory to other treatments. Metamizole is a relatively safe drug. It seems that in the past the risk of metamizole-induced agranulocytosis was overdrew. Metamizole is contraindicated in pregnancy and breastfeeding women. Paracetamol overdose can lead to acute hepatic and renal failure. Paracetamol monotherapy, on condition that the drug is administered at therapeutic doses, is well tolerated by the majority of patients. On another hand, according to the previous study, a long-term application of paracetamol may increase the risk of adverse reactions typical for COX-2 inhibitors such as hypertension, heart infarction or renal failure. However, up to now paracetamol remains still the drug of choice for treating minor to moderate pain in pregnant women and in patients with coagulation, renal or cardiovascular disorders. Copyright © Via 2016 Medica120729O field[22]: [Metamizole and paracetamol - Similar but not the same drugs]. In Polish with English abstract Not in File8?lKucharska, G. Filipska, M. Adamczyk, P. Lipiec, K. Roszkowska-Bjanid, D. Trembecka-Dubel, E. Szczepanska, M.2016:Ostre uszkodzenie nerek w przebiegu zatrucia metamfetamina496-501Pediatria Polska915ACCIDENTAL ACIDOSIS ACUTE Acute kidney injury AMFETAMINE amphetamine As author BLOOD BLOOD PRESSURE case chemical CHILDREN CLINICAL COMA Confirmation Convulsion CONVULSIONS CREATININE DEATH DIAGNOSIS FAILURE glomerular hemodialysis HI history HYPERGLYCAEMIA HYPERTHERMIA IDENTIFICATION IMPAIRMENT INGESTION injuries Injury INTOXICATION IS KIDNEY kidney injury Laboratories LABORATORY laboratory tests LEAD MALIGNANT METABOLIC ACIDOSIS METHAMPHETAMINE NEPHROTOXICITY NEUROLEPTIC MALIGNANT SYNDROME PATIENT pediatric Qualitative Reduction RENAL RENAL FUNCTION Renal replacement therapy RHABDOMYOLYSIS STUDY Syndrome TACHYCARDIA TEST THERAPY toxic TREATMENT use WHO youth2016"Designer drugs", which act as psychoactive substances, are nowadays applied more often by younger children. They are the mixture of many substances of unknown chemical composition, so it is difficult to predict life-threatening consequences of their use. Currently amphetamine and its derivatives are very popular among the Polish youth. Methamphetamine is one of the fastest and most addictive psychoactive substances. Its use can cause a complex of life-threatening consequences, among them neuroleptic malignant syndrome (including hyperthermia, convulsions and coma), as well as tachycardia, high blood pressure, dehydration, rhabdomyolysis and acute kidney injury. The authors present a case of 17.5-year-old boy who presented with acute kidney injury and other metabolic disorders after consuming the product "crystal" that contained derivatives of methamphetamine. The boy was transferred to the Department of Nephrology in severe general condition with the qualitative and quantitative disorders of consciousness. In laboratory tests hyperglycaemia, metabolic acidosis, increased transaminases and creatinine kinase activity and features of acute renal injury with a significant reduction in glomerular filtration rate (eGFR-13.1 ml/min/1.73 m2) were found. Toxicological studies did not allow for the identification of potentially toxic substance. The patient required renal replacement therapy (five hemodialysis sessions) and intensive symptomatic treatment. During the diagnostics the boy finally declared occasional application of various psychoactive substances, and confirmed ingestion of the methamphetamine derivative substance on the day of the event. The history of the patient revealed that the lack of toxicological confirmation of the presence of substances in the body, and the denial of contact with these products by the patient and his relatives do not rule out the diagnosis of intentional or accidental intoxication. Severe clinical course, frequently complicated by acute kidney injury or multiorgan failure, indicates that the lack of timely intervention could lead to permanent impairment of renal function or even death of the patient. Copyright © 2016 Polish Pediatric Society120742, field[22]: [Acute kidney injury due to methamphetamine intoxication]. In Polish with English abstract RefMgr field[33]: Not in File?#Kumar, S. Reddy, C.R. Prabhakar, S.2016JBilateral putaminal necrosis in a comatose patient with metabolic acidosis745-748(Indian Journal of Critical Care Medicine2012ACIDOSIS ALCOHOL BLINDNESS BRAIN case COMA DIAGNOSIS history HYPOTENSION Imaging INGESTION IS MAGNETIC RESONANCE magnetic resonance imaging METABOLIC ACIDOSIS METHANOL methyl alcohol NECROSIS PATIENT RESPIRATORY respiratory distress Toxicities TOXICITY12/2016We present a case of acute-onset coma in a young woman, associated with metabolic acidosis, respiratory distress, and hypotension. Magnetic resonance imaging of the brain done on day 2 of admission showed features of bilateral putaminal necrosis. History of methanol ingestion, though not forthcoming at admission, was confirmed later after the patient regained consciousness. A final diagnosis of methyl alcohol toxicity resulting in severe metabolic acidosis, coma, and bilateral blindness was made. This case is reported to emphasize the point that the finding of bilateral putaminal necrosis in a patient with coma and metabolic acidosis is virtually diagnostic of methyl alcohol toxicity even in the absence of any positive history120732* field[33]: year=2016 volume=20 issue=12 spage=745 epage=748 aulast=Kumar Not in File ?lLamy, S. Hennart, B. Houivet, E. Dulaurent, S. Delavenne, H. Benichou, J. Allorge, D. Marret, S. Thibaut, F.2017Assessment of tobacco, alcohol and cannabinoid metabolites in 645 meconium samples of newborns compared to maternal self-reports86-93Journal of Psychiatric Research90ADDICTION ALCOHOL As ASSESSMENT Biomarker BIOMARKERS CANNABINOID CANNABIS child Child development Cotinine DETECTION Development ETHYL GLUCURONIDE EXPOSURE FETAL Fetal exposure HEALTH impact IS LEVELS Measurement MECONIUM METABOLITE Metabolites MOTHERS NEONATAL PAEDIATRIC PREDICTION PREGNANCY PRENATAL Prenatal exposure prevalence RISK self-report SEVERITY STUDY Testing Time TOBACCO use 2/13/2017Prenatal psychoactive substance exposure has significant impact on neonatal health and child development and the development of reliable biomarkers is critical. Meconium presents several advantages for detecting prenatal exposure to psychoactive substances, as it is easy to collect and provides a broad time frame of exposure (third trimester). The aim of our study was to compare the prevalence of alcohol, tobacco and/or cannabis use during the third trimester of pregnancy (using maternal self-reports) with the results of meconium testing of their metabolites in newborns (cotinine, ethyl-glucuronide (EtG) and cannabinoid metabolites). Among all deliveries (993) that occurred in all maternities in Rouen (Normandy) during a defined time period (5 consecutive weeks in August, 2010 and August, 2011), 724 mothers were included and 645 meconium samples were collected. Maternal self-reports, using the Addiction Severity Index (5th edition), and meconium samples were collected within 72 h of delivery. Cotinine detection appears highly correlated to maternal self-reports (Kappa value: 0.79; [95%CI: 0.73-0.85]). Moreover, detection in meconium seems more accurate in the prediction of neonatal consequences of prenatal tobacco exposure as compared to maternal self-reports. In contrast, we have found a lower concordance between maternal self-reports and meconium testing for EtG and cannabinoid metabolites (Kappa value: 0.13; [95%CI: 0.04-0.22] and: 0.30; [95%CI: -0.03-0.63], respectively); however the total number of EtG- and cannabinoid-positive meconium samples was small. Interestingly, meconium samples with the highest levels of EtG mainly corresponded to negative maternal self-reports. Fetal exposure to alcohol, tobacco or cannabis may also considerably differ as displayed in our pairs of dizygotic twins. Finally, a polyconsumption of these psychoactive substances was not frequently observed according to meconium testing. In conclusion, cotinine detection appears as a valuable meconium biomarker. EtG measurement in meconium samples seems interesting if there is any risk of high fetal exposure, whereas assessment of prenatal cannabis exposure, using meconium testing, needs to be improved1210612 field[33]: Not in FileB?Lands, H.M. Drake, D.B.2017=A medical mystery: unexplained renal failure in burn patientsJournal of Burn Care & Research/online early: doi: 10.1097/BCR.0000000000000500not published, 16 Feb 17AACIDOSIS ANTIMICROBIAL As author BASE Burn BURNS case CASE REPORT case reports Case-report DERMAL DRUG FAILURE GAP hypercalcemia LATE PATIENT POLYETHYLENE POLYETHYLENE GLYCOL Pseudomonas RENAL RENAL FAILURE REVIEW Side effect side effects side-effects SILVER Source STUDY SULFADIAZINE Syndrome TOPICAL Toxicities TOXICITY 1/31/2017sThe objective of this study was to review the investigation that uncovered the medical mystery of burn patients developing unexpected renal failure. The authors examined published and unpublished manuscripts and case reports, as well as conducted personal interviews with primary sources. In the late 1970s, emergence of resistant bacterial strains to the topical antimicrobial silver sulfadiazine occurred at the University of Virginia Medical Center. In the search for an alternative topical antimicrobial with known coverage of Pseudomonas aeruginosa, Furacin Soluble Dressing was substituted. However, Furacin Soluble Dressing produced an unexpected toxicity syndrome of hyperosmolality, metabolic gap acidosis, hypercalcemia, and ultimately renal failure. In a search for an antimicrobial with an improved spectrum against Pseudomonas, a Federal Drug Administration-approved product was used to treat large surface area burns. An unexpected toxicity syndrome developed which was traced to the polyethylene glycol base of Furacin Soluble Dressing. This substance was absorbed through the burn wounds, metabolized, and resulted in a toxicity syndrome leading to renal failure. The burn community should be cautious when using products that may be approved as nontoxic for small surface area application, as they may have unexpected medical side effects when used with large surface area burns120727. field[33]: Not in FilewB?MLatasiewicz, M. Gourier, H. Yusuf, I.H. Luqmani, R. Sharma, S.M. Downes, S.M.20173Hydroxychloroquine retinopathy: an emerging problem Eye (Lond)'online early: doi: 10.1038/eye.2016.297not published, 28 Feb 17Awareness case CHLOROQUINE DETECTION HYDROXYCHLOROQUINE Imaging IS Long term Long-term MONITORING OCULAR PATIENT PUBLICATION RETINOPATHY RHEUMATOID ARTHRITIS SCREENING SEVERITY SURVIVAL SYSTEMIC Testing TOMOGRAPHY Toxicities TOXICITY use WHO 2/10/2017jPurposeThe aim of this case series is to raise awareness of the emerging issue of serious retinal damage caused by the prolonged use of hydroxychloroquine (HCQ) and the importance of adequate and appropriate monitoring of visual function during treatment.Patient and methodsThis is a small retrospective case series of 3 patients on long-term HCQ who developed serious symptomatic retinal toxicity confirmed on imaging and functional testing.ResultsAll 3 patients were treated with HCQ for over 15 years; two for rheumatoid arthritis (RA), and the third for systemic lupus erythematosus (SLE). All 3 patients had macular involvement varying in severity confirmed with characteristic features on imaging and functional testing (Optical Coherence Tomography (OCT), Autofluorescence (AF) and Humphrey 10-2 visual fields).ConclusionHCQ is widely used to treat autoimmune conditions with a proven survival benefit in patients with SLE. However, long-term use can be associated with irreversible retinal toxicity. These cases highlight that HCQ, like chloroquine, can also cause visual loss in susceptible individuals. Early detection of presymptomatic retinal changes by the introduction of appropriate screening and monitoring is mandatory to limit the extent of irreversible visual loss due to HCQ retinal toxicity.Eye advance online publication, 10 February 2017; doi:10.1038/eye.2016.297120881& field[33]: Not in FilesB?ULaulicht Glick, F. Wu, F. Zhang, X. Jordan, A. Brocato, J. Kluz, T. Sun, H. Costa, M.2017HTungsten exposure causes a selective loss of histone demethylase proteinMolecular Carcinogenesis#online early: doi: 10.1002/mc.22634not published, 01 Mar 17CELL DRINKING WATER EXPOSURE IS LEVELS LIVER MICE PROTEIN proteins SODIUM sodium tungstate Toxicities TOXICITY TREATMENT TUNGSTEN WATER 2/20/2017In the course of our investigations into the toxicity of tungstate, we discovered that cellular exposure resulted in the loss of the histone demethylase protein. We specifically investigated the loss of two histone demethylase dioxygenases, JARID1A and JMJD1A. Both of these proteins were degraded in the presence of tungstate and this resulted in increased global levels of H3K4me3 and H3K9me2, the substrates of JARID1A and JMJD1A respectively. Treatment with MG132 completely inhibited the loss of the demethylase proteins induced by tungstate treatment, suggesting that tungstate activated the proteasomal degradation of these proteins. The changes in global histone marks and loss of histone demethylase protein persisted for at least 48 hours after removing sodium tungstate from the culture. The increase in global histone methylation remained when cells were cultured in methionine-free media, indicating that the increased histone methylation did not depend upon any de novo methylation process, but rather was due to the loss of the demethylase protein. Similar increases of H3K4me3 and H3K9me2 were observed in the livers of the mice that were acutely exposed to tungstate via their drinking water. Taken together, our results indicated that tungstate exposure specifically reduced histone demethylase JARID1A and JMJD1A via proteasomal degradation, leading to increased histone methylation. This article is protected by copyright. All rights reserved121074" field[33]: Not in File?ZLaustsen, A.H. Engmark, M. Milbo, C. Johannesen, J. Lomonte, B. Gutiérrez, J.M. Lohse, B.2016FFrom fangs to pharmacology: the future of snakebite envenoming therapy 5270-5293Current Pharmaceutical Design2234nAfrica ANIMAL Animals ANTITOXIN ANTIVENOM Asia Association bioinformatics CHEMISTRY DATA Development DRUG Drug design EFFICACY envenoming HAZARD HEALTH Health hazard IMMUNIZATION impact IS Medicine PARENTERAL PHARMACOLOGY PUBLIC PUBLIC HEALTH REVIEW SAFETY snake bite SNAKE VENOM SNAKEBITE snakebite envenoming Snakes SPECIES THERAPY toxin TOXINS TREATMENT use Venom2016DThe snake is the symbol of medicine due to its association with Asclepius, the Greek God of medicine, and so with good reasons. More than 725 species of venomous snakes have toxins specifically evolved to exert potent bioactivity in prey or victims, and snakebites constitute a public health hazard of high impact in Asia, Africa, Latin America, and parts of Oceania. Parenteral administration of antivenoms is the mainstay in snakebite envenoming therapy. However, despite well-demonstrated efficacy and safety of many antivenoms worldwide, they are still being produced by traditional animal immunization procedures, and therefore present a number of drawbacks. Technological advances within biopharmaceutical development and medicinal chemistry could pave the way for rational drug design approaches against snake toxins. This could minimize the use of animals and bring forward more effective therapies for snakebite envenomings. In this review, current stateof-the-art in biopharmaceutical antitoxin development is presented together with an overview of available bioinformatics and structural data on snake venom toxins. This growing body of scientific and technological tools could define the basis for introducing a rational drug design approach into the field of snakebite envenoming therapy. Copyright © 2016 Bentham Science Publishers1208253<RefMgr field[33]: Not in File#?8Laustsen, A.H. Johansen, K.H. Engmark, M. Andersen, M.R.2017^Recombinant snakebite antivenoms: a cost-competitive solution to a neglected tropical disease?e0005361 PLoS Neglected Tropical Diseases112Africa ANTIBODIES ANTIVENOM burden CELL COST DATA DISEASE DRUG envenoming HEALTH HUMAN impact IS LIMB PUBLIC PUBLIC HEALTH snake bite SNAKEBITE snakebite envenoming THERAPEUTIC THERAPY TREATMENT VACCINE2/3/20177Snakebite envenoming is a major public health burden in tropical parts of the developing world. In sub-Saharan Africa, neglect has led to a scarcity of antivenoms threatening the lives and limbs of snakebite victims. Technological advances within antivenom are warranted, but should be evaluated not only on their possible therapeutic impact, but also on their cost-competitiveness. Recombinant antivenoms based on oligoclonal mixtures of human IgG antibodies produced by CHO cell cultivation may be the key to obtaining better snakebite envenoming therapies. Based on industry data, the cost of treatment for a snakebite envenoming with a recombinant antivenom is estimated to be in the range USD 60-250 for the Final Drug Product. One of the effective antivenoms (SAIMR Snake Polyvalent Antivenom from the South African Vaccine Producers) currently on the market has been reported to have a wholesale price of USD 640 per treatment for an average snakebite. Recombinant antivenoms may therefore in the future be a cost-competitive alternative to existing serum-based antivenoms120726.[RefMgr field[33]: Not in FileB?JLevine, M. Stellpflug, S. Pizon, A.F. Traub, S. Vohra, R. Wiegand, T. Traub, N. Tashman, D. Desai, S. Chang, J. Nathwani, D. Thomas, S.2017tEstimating the impact of adopting the revised United Kingdom acetaminophen treatment nomogram in the U.S. populationClinical Toxicology0online early: doi: 10.1080/15563650.2017.1291945not published, 03 Mar 17ACETAMINOPHEN ACUTE acute poisoning Age burden CLINICAL COST EXPOSURE HOSPITAL impact IS NOMOGRAM PARACETAMOL PATIENT POISONING Population REVIEW STUDY Toxicities TOXICITY TREATMENT United Kingdom UNITED STATES WHO3/1/2017sBackground: Acetaminophen toxicity is common in clinical practice. In recent years, several European countries have lowered the treatment threshold, which has resulted in increased number of patients being treated at a questionable clinical benefit.Objective: The primary objective of this study is to estimate the cost and associated burden to the United States (U.S.) healthcare system, if such a change were adopted in the U.S.Methods: This study is a retrospective review of all patients age 14 years or older who were admitted to one of eight different hospitals located throughout the U.S. with acetaminophen exposures during a five and a half year span, encompassing from 1 January 2008 to 30 June 2013. Those patients who would be treated with the revised nomogram, but not the current nomogram were included. The cost of such treatment was extrapolated to a national level.Results: 139 subjects were identified who would be treated with the revised nomogram, but not the current nomogram. Extrapolating these numbers nationally, an additional 4507 (95%CI 3641?8751) Americans would be treated annually for acetaminophen toxicity. The cost of lowering the treatment threshold is estimated to be $45 million (95%CI 36,400,000?87,500,000) annually.Conclusions: Adopting the revised treatment threshold in the U.S. would result in a significant cost, yet provide an unclear clinical benefit121159/ field[33]: Not in FileB??Li, N. Liu, Y. Qiu, J. Zhong, L. Alepee, N. Cotovio, J. Cai, Z.2017pIn vitro skin irritation assessment becomes a reality in China using a reconstructed human epidermis test methodToxicology in Vitro,online early: doi: 10.1016/j.tiv.2017.02.009not published, 01 Mar 17ACUTE ANIMAL As ASSESSMENT chemical CHEMICALS China DERMAL EPISKIN EVALUATION HUMAN IN VITRO IRRITATION Laboratories LABORATORY MET method methods MODEL Sensitivity SKIN TEST Testing 2/17/2017DThe in vitro EpiSkin test method was validated in 2007 by the European Union Reference Laboratory for alternatives to animal testing (EURL ECVAM) as a full replacement method for the Draize acute skin irritation test and adopted in the OECD Test Guideline 439 in 2009. Based on the EpiSkin technology, the production of a reconstructed epidermis model has been established and standardized in China. The evaluation of the in vitro skin irritation test method using this EpiSkin model produced in China was performed on a set of 45 chemicals. Good predictive capacity was obtained with 94% (n=17) for sensitivity, 75% (n=28) for specificity and 82% for accuracy. The accuracy of the included 20 OECD reference chemicals also met the OECD acceptance criteria, indicating that this testing method based on the EpiSkin model produced in China can be used as a stand-alone test method to predict skin irritation. The availability and validity of in vitro epidermis model and testing method are of great significance for extending the applications of non-animal alternative testing methods in China121125+ field[33]: Not in File Z?+Li, Q. Davila, J. Bagchi, M.K. Bagchi, I.C.2016uChronic exposure to bisphenol A impairs progesterone receptor-mediated signaling in the uterus during early pregnancye1369"Receptors & Clinical Investigation33Affect Attention Bisphenol A BISPHENOL-A CELL chemical CHEMICALS CHRONIC Chronic exposure Differentiation dose Embryo ENDOCRINE ENVIRONMENTAL EPOXY RESINS ESTROGENIC ACTIVITY EXPOSURE FEMALE GROWTH GROWTH FACTOR HEALTH HUMAN impact IMPAIRMENT IS maintenance MECHANISM Mechanisms MISCARRIAGE OCCUPATIONAL OCCUPATIONAL EXPOSURE Pathway PLASTICS POLYCARBONATE PREGNANCY PROGESTERONE PUBLICATION reprotoxicity RESEARCH RESIN RISK STUDY Toxicant UTERUS WOMEN2016Environmental and occupational exposure to endocrine disrupting chemicals (EDCs) is a major threat to female reproductive health. Bisphenol A (BPA), an environmental toxicant that is commonly found in polycarbonate plastics and epoxy resins, has received much attention due to its estrogenic activity and high risk of chronic exposure in human. Whereas BPA has been linked to infertility and recurrent miscarriage in women, the impact of its exposure on uterine function during early pregnancy remains unclear. In a recent publication in Endocrinology, we demonstrated that prolonged exposure to an environmental relevant dose of BPA disrupts progesterone receptor-regulated uterine functions, thus affecting uterine receptivity for embryo implantation and decidua morphogenesis, two critical events for establishment and maintenance of early pregnancy. In particular we reported a marked impairment of progesterone receptor (PGR) expression and its downstream effector HAND2 in the uterine stromal cells in response to chronic BPA exposure. In an earlier study we have shown that HAND2 controls embryo implantation by repressing fibroblast growth factor (FGF) expression and the MAP kinase signaling pathway, thus inhibiting epithelial proliferation. Interestingly we observed that downregulation of PGR and HAND2 expression in uterine stroma upon BPA exposure was associated with an enhanced activation of FGFR and MAPK signaling, aberrant proliferation, and lack of uterine receptivity in the epithelium. In addition, the proliferation and differentiation of endometrial stromal cells to decidual cells, an event critical for the maintenance of early pregnancy, was severely compromised in response to BPA. This research highlight will provide an overview of our findings and discuss the potential mechanisms by which chronic BPA impairs PGR-HAND2 pathway and adversely affects implantation and the establishment of pregnancy121097# field[33]: Not in File?2Lin, Z. Li, J. Zhang, X. Qiu, M. Huang, Z. Rao, Y.2017Ultrasound-assisted dispersive liquid-liquid microextraction for the determination of seven recreational drugs in human whole blood using gas chromatography-mass spectrometry177-184Journal of Chromatography B1046ABUSE Affect amphetamine ANALYTICAL BLOOD Blood samples DETECTION determination DRUG DRUG ABUSE drugs EXTRACTION GA GAS gas chromatography mass spectrometry Gas chromatography-mass spectrometry HEALTH HUMAN Human whole blood impact IS KETAMINE limits MEPERIDINE METHADONE METHAMPHETAMINE method pH PUBLIC PUBLIC HEALTH quantification recovery RECREATIONAL DRUGS SOLVENT Solvents SPECTROMETRY STUDY SUBSTANCE ABUSE Time Volume 1/22/2017Recreational drugs have large impact on public health and security, and to monitor them is of urgent demand. In the present study, ultrasound-assisted dispersive liquid-liquid microextraction combined with the detection of gas chromatography-mass spectrometry was applied to the determination of seven common recreational drugs, including amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, meperidine, methadone and ketamine in 200muL of human whole blood. A series of factors which would affect the extraction efficiency were systematically investigated, including the nature and the volume of extraction and dispersing solvents, ultrasonication time, salting-out effect and pH value. The method consumed small amount of sample. The limits of detection and limits of quantification for each analyte were 10 and 40ng/mL, respectively, and the linearity was in the range of 0.04-25mug/mL (R2 higher than 0.99). Good specificity, precision (1.5-8.2% for the intra-day study and 2.6-12.8% for the inter-day study), satisfactory accuracy (85.0-117.1%) and extraction recovery (77.0-92.4%) were obtained, which makes it a high performance method for the determination of recreational drugs in human whole blood samples120897/ field[33]: Not in File 8?^Liu, X. Lao, X.Q. Wong, C.C.-Y. Tan, L. Zhang, Z. Wong, T.W. Tse, L.-A. Lau, A.P.S. Yu, I.T.S.2016[Frequent use of household cleaning products is associated with rhinitis in Chinese children 754-760.e6*Journal of Allergy and Clinical Immunology1383As author burden chemical CHILDREN CHINESE EXPOSURE HEALTH Health effects HOME HOUSEHOLD household products INFORMATION IS method methods NO Odds Ratio PAEDIATRIC QUESTIONNAIRE RESPIRATORY RESPIRATORY SYMPTOMS RHINITIS School STUDY SYMPTOMS Time use WATER2016Background Despite the popular use of household cleaning products worldwide, there is no published study investigating the health effects of these products on rhinitis in children. Objective We sought to investigate the household use of cleaning products and rhinitis patterns in Chinese children. Methods A total of 2299 children were recruited from 21 primary schools with wide geographic coverage in Hong Kong. Self-administered questionnaires were completed by parents/guardians to collect detailed information on respiratory symptoms and household use of 14 types of chemical cleaning products, as well as clean water. Students were categorized into 4 mutually exclusive rhinitis patterns (never, occasional, frequent, and persistent). The total chemical burden (TCB) score was used as the exposure indicator by calculating the total time of exposure to the 14 cleaning products. Multinomial logistic regression was used to assess the relationship between rhinitis patterns and the use of household cleaning products. Results Every 10-unit increment of TCB score was associated with an increase in the odds of occasional (odds ratio [OR], 1.21; 95% CI, 1.05-1.41), frequent (OR, 1.36; 95% CI, 1.13-1.60), and persistent (OR, 1.21; 95% CI, 1.01-1.56) rhinitis after adjustment for a wide range of potential confounders. Compared with the children within the lowest tertile of TCB scores, the adjusted ORs of occasional, frequent, and persistent rhinitis in children within the highest tertile were 1.29 (95% CI, 1.01-1.65), 1.97 (95% CI, 1.40-2.76), and 1.67 (95% CI, 1.10-2.54), respectively. Conclusion Frequent use of chemical cleaning products at home is associated with an increase in the odds of rhinitis in Chinese primary school children. Copyright © 2016 The Authors120736, field[33]: Not in File XB?CLiu, X. Yang, J. Lu, C. Jiang, S. Nie, X. Han, J. Yin, L. Jiang, J.2017jDownregulation of Mfn2 participates in manganese-induced neuronal apoptosis in rat striatum and PC12 cellsNeurochemistry International/online early: doi: 10.1016/j.neuint.2017.02.008not published, 01 Mar 174analysis apoptosis BRAIN brain function CELL CHRONIC Chronic exposure CLINICAL cognitive Cognitive deficits CONCENTRATIONS Development DISEASE evidence EXPOSURE IS LEAD MANGANESE MECHANISM motor neurodegeneration neuron NEUROTOXICITY Parkinson's disease PROTEIN RAT rat striatum Regulation Syndrome TREATMENT 2/20/2017Manganese (Mn) is a widely distributed trace element that is essential for normal brain function and development. However, chronic exposure to excessive Mn has been known to lead to neuronal loss and manganism, a disease with debilitating motor and cognitive deficits, whose clinical syndrome resembling idiopathic Parkinson's disease (IPD). However, the precise molecular mechanism underlying Mn neurotoxicity remains largely unclear. Accumulating evidence indicates that abnormal mitochondrial functionality is an early and causal event in Mn-induced neurodegeneration and apoptosis. Here, we investigated whether Mitofusin 2 (Mfn2), a highly conserved dynamin-related protein (DRP), played a role in the regulation of Mn-induced neuronal apoptosis. We revealed that Mfn2 was significantly dysregulated in rat striatum and PC12 neuronal-like cells following Mn exposure. Western blot analysis revealed that the expression of Mfn2 was remarkably decreased following different concentrations of Mn exposure. Immunohistochemistry analysis confirmed a remarkable downregulation of Mfn2 in rat striatum after Mn exposure. Immunofluorescent staining showed that Mfn2 was expressed predominantly in neurons, and neuronal loss of Mfn2 was associated with the expression of active caspase-3 following Mn exposure. Importantly, overexpression of Mfn2 apparently attenuated Mn-induced neuronal apoptosis. Notably, treatment with caspase-3 inhibitor Ac-DEVD-CH could not rescue Mn-induced downregulation of Mfn2, suggesting that Mn-induced mfn2 occurs prior to neuronal apoptosis. Taken together, these results indicated that down-regulated expression of Mfn2 might contribute to the pathological processes underlying Mn neurotoxicity121077. field[33]: Not in File B?"Liu, Z. Wang, X. Wang, Y. Zhao, M.2017qNLRP3 inflammasome activation regulated by NF-kappaB and DAPK contributed to paraquat-induced acute kidney injury Immunol Res,online early: doi: 10.1007/s12026-017-8901-7not published, 01 Mar 17WACUTE Acute kidney injury ANIMAL CELL CLINICAL cytokine CYTOKINES ELISA EXPOSURE HUMAN Inflammasome INGESTION INJECTION injuries Injury INTRAPERITONEAL KIDNEY kidney injury MALE MECHANISM Mechanisms Multiple organs NECROSIS NEPHROTOXICITY Organs PARAQUAT PROTEIN RAT rats Regulation RENAL STUDY toxic toxic effects tumor Wistar rat Wistar rats 2/18/2017aParaquat can result in dysfunction of multiple organs after ingestion in human. However, the mechanisms of nucleotide-binding domain and leucine-rich repeat containing protein 3 (NLRP3) inflammasome activation in acute kidney injury have not been clearly demonstrated. The aim of this study was to determine the effect of NLRP3 inflammasome activation and its regulation by nuclear factor-kappa B (NF-kappaB) and death-associated protein kinase (DAPK). Male Wistar rats were treated with intraperitoneal injection of paraquat at 20 mg/kg, and NF-kappaB inhibitor BAY 11-7082 was pretreated at 10 mg/kg 1 h before paraquat exposure. Additionally, rat renal tubular epithelial cells (NRK-52E) were transfected with small interfering RNA (siRNA) against DAPK to evaluate its role in NLRP3 inflammasome activation. DAPK and NLRP3 inflammasome were evaluated by immunohistochemistry staining or Western blot; the pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-18 (IL-18) were measured via ELISA. The results showed that NF-kappaB, DAPK, and NLRP3 inflammasome were activated in paraquat (PQ)-treated rat kidney; the secretion of pro-inflammatory cytokines was significantly increased. These toxic effects were attenuated by NF-kappaB inhibitor. Besides, the activation of NLRP3 inflammasome and secretion of IL-1beta and IL-18 in paraquat-treated rat renal tubular epithelial cells were inhibited by siRNA against DAPK. In conclusion, NLRP3 inflammasome activation regulated by NF-kappaB and DAPK played an important role in paraquat-induced acute kidney injury121020+ field[33]: Not in FiletB?ZLones, C.E. Bond, G.R. McGovern, M.P. Carr, K. Leckron-Myers, T. Hartnett, T. Becker, D.R.2017vIndividual Placement and Support (IPS) for methadone maintenance therapy patients: a pilot randomized controlled trialNAdministration and Policy in Mental Health and Mental Health Services Research,online early: doi: 10.1007/s10488-017-0793-2not published, 01 Mar 170ABUSE As COMPARISON effectiveness EMPLOYMENT EVIDENCE-BASED FOLLOW UP Follow-up ILLNESS IS maintenance maintenance treatment METHADONE Methadone maintenance Methadone maintenance therapy MODEL OPIOID Opioid Treatment opioid use disorder outcome P PATIENT STUDY SUBSTANCE ABUSE THERAPY TREATMENT TRIAL use 2/17/2017Individual Placement and Support (IPS) is an evidence-based employment model for people with severe mental illness, but it has not been evaluated for clients enrolled in substance abuse treatment programs. This study evaluated the effectiveness of IPS for people with opioid use disorders enrolled in an opioid treatment program. Within a randomized controlled experiment, 45 patients receiving methadone maintenance therapy were assigned to either IPS or a 6-month waitlist. The waitlist group received IPS after 6 months. The primary outcome assessed over 1 year compared the attainment of a job for the IPS condition to the waitlist comparison group. During the first 6 months after enrollment, 11 (50%) active IPS participants gained competitive employment compared to 1 (5%) waitlist participant (Chi 2 = 12.0, p < 0.001). Over 12 months of enrollment, 11 (50%) IPS participants gained competitive employment compared to 5 (22%) waitlist participants (Chi 2 = 3.92, p = 0.07). We conclude that IPS holds promise as an employment intervention for people with opioid use disorders in methadone maintenance treatment, but larger trials with longer follow-up are needed120932+ field[33]: Not in File yB?López-Arnau, R. Buenrostro-Jáuregui, M. Muñoz-Villegas, P. Rodríguez-Morató, J. Ciudad-Roberts, A. Duart, L. Camarasa, J. de la Torre, R. Pubill, D. Escubedo, E.2017The combination of MDPV and ethanol results in decreased cathinone and increased alcohol levels. Study of such pharmacological interaction)Prog Neuropsychopharmacol Biol early: doi: 10.1016/j.pnpbp.2017.02.011not published, 01 Mar 17ALCOHOL As ASSAY BLOOD BRAIN CATHINONE Cathinones CONCENTRATIONS Consumption DOPAMINE dose ELIMINATION ETHANOL impact INTERACTION IS LEVELS LIVER Locomotor activity Low doses MDPV METABOLISM METHYLENEDIOXYPYROVALERONE MICRODIALYSIS MICROSOME new psychoactive substance NEW PSYCHOACTIVE SUBSTANCES NOVEL PSYCHOACTIVE SUBSTANCES PLASMA Psychostimulant RAT rats Reduction stimulant STUDY synthetic cathinone Synthetic cathinones transporter 2/17/2017Methylenedioxypyrovalerone (MDPV) is a new psychostimulant cathinone acting as a selective dopamine transporter blocker. Due to the concomitant consumption of ethanol (EtOH) and new psychoactive substances, it is of interest to explore a possible pharmacological interaction between MDPV and EtOH. In locomotor activity assays, EtOH (1g/kg i.p.) elicited a reduction in the stimulant effect induced by low doses of MDPV (0.1-0.3mg/kg, s.c.) in rats, jointly with a decrease in blood and brain MDPV concentrations. Experiments in rat liver microsomes showed different effects depending on the [MDPV]/[EtOH] relationship, evidencing, at certain concentrations, the enhancing effect of EtOH on MDPV metabolism. These suggest that EtOH interacts with MDPV at microsomal level, increasing its metabolic rate. The interaction between both substances was also supported by results in plasma EtOH concentration, which were significantly increased by MDPV, in such a manner that EtOH elimination rate was significantly reduced. The possible toxicological impact of this phenomenon deserves further investigation. In contrast, the rewarding properties of MDPV were unaltered by EtOH. Microdialysis experiments verified that, in the NAcc, both substances could also act synergistically, in such a manner that extracellular dopamine concentrations are maintained. Finally, if the psychostimulant effect induced by MDPV decreased with EtOH, it could favor the boosting and re-dosing in search of the desired effects. However, as the rewarding effect of each dose of the substance would not decrease, the addictive liability could increase considerably. Moreover, we must warn about the increase in EtOH concentrations when consumed concomitantly with MDPV121094- field[33]: Not in FileB?MLu, J. Zhang, P. Zou, X. Zhao, X. Cheng, K. Zhao, Y. Bi, Y. Zheng, M. Luo, X.2017KIn silico prediction of chemical toxicity profile using local lazy learning5Combinatorial Chemistry and High Throughput Screening4online early: doi: 10.2174/1386207320666170217151826not published, 01 Mar 17ACUTE Acute toxicity As Bayesian BAYESIAN MODEL chemical dose DRUG drugs EYE eye irritation FAILURE in silico IRRITATION IS IV method MODEL MUTAGENICITY PREDICTION RESEARCH SKIN STUDY TEST Toxicities TOXICITY Toxicity profile 2/17/2017Chemical toxicity is an important reason for late-stage failure in drug R&D. However, it is time-consuming and expensive to identify the multiple toxicities of compounds using the traditional experiments. Thus, it is attractive to build an accurate prediction model for the toxicity profile of compounds. In this study, we carried out a research on six types of toxicities: (I) Acute Toxicity; (II) Mutagenicity; (III) Tumorigenicity; (IV) Skin and Eye Irritation; (V) Reproductive Effects; (VI) Multiple Dose Effects, using local lazy learning (LLL) method for multi-label learning. 17,120 compounds were split into the training set and the test set as a ratio of 4:1 by using the Kennard-Stone algorithm. Four types of properties, including molecular fingerprints (ECFP_4 and FCFP_4), descriptors, and chemical-chemical-interactions, were adopted for model building. The model 'ECFP_4+LLL' yielded the best performance for the test set, while balanced accuracy (BACC) reached 0.692, 0.691, 0.666, 0.680, 0.631, 0.599 for six types of toxicities, respectively. Furthermore, the prediction ability of the 'ECFP_4+LLL' model was tested and verified by two external sets. Finally, some essential toxicophores for six types of toxicities were identified by using the Laplacian-modified Bayesian model. We wish that the accurate prediction model and the chemical toxicophores can provide some guidance for designing drugs with lower toxicity1209723 field[33]: Not in File}B??Lusthof, K.J. Bosman, I.J. Kubat, B. Vincenten-van Maanen, M.J.2017]Toxicological results in a fatal and two non-fatal cases of scopolamine-facilitated robberiesForensic Science International2online early: doi: 10.1016/j.forsciint.2017.01.024not published, 01 Mar 17As BLOOD blood concentration case CONCENTRATIONS CRIME DERMAL dose DRUG FATAL FORENSIC HAIR HEART IS LEVELS PATCH POSTMORTEM SCOPOLAMINE SERUM STOMACH THERAPEUTIC Time URINE use2/4/2017nThe use of scopolamine as an incapacitating drug, in sexual crimes and robberies, has been known for many decades. However, blood concentrations and doses of scopolamine in those cases are largely unknown. Here we present the toxicological results of one fatal and two non-fatal cases in a series of scopolamine-facilitated robberies. In the fatal case, the concentration of scopolamine in heart blood was 0.30mg/L, about 3000 times higher than the average therapeutic level of 0.0001mg/L (for one dermal patch). In femoral blood, the concentration of scopolamine was much lower (0.0048mg/L), but still 50 times higher than therapeutic levels. The scopolamine concentration in the stomach was very high (20mg/kg) as compared to the heart blood and femoral blood, which explains the very high concentration in heart blood by postmortem leakage from the stomach. In the non-fatal case, the scopolamine concentration in serum, obtained 23h after the incident, was 0.00035mg/L. The estimated concentration of scopolamine at the time of the incident is 0.0035mg/L. In the other non-fatal case, scopolamine was detected in urine and in hair1210141 field[33]: Not in File hB?MLydon, H.L. Hall, C.A. Dalton, C.H. Chipman, J.K. Graham, J.S. Chilcott, R.P.2017Development of haemostatic decontaminants for treatment of wounds contaminated with chemical warfare agents. 3: Evaluation of in vitro topical decontamination efficacy using damaged skinJournal of Applied Toxicology#online early: doi: 10.1002/jat.3446not published, 01 Mar 17kABSORPTION ACUTE acute poisoning agent ANIMAL chemical chemical warfare CLINICAL DATA DECONTAMINATION DERMAL dermal absorption Development effectiveness EFFICACY EVALUATION HD IN VITRO injuries Injury john MANAGEMENT MECHANISM mechanism of action MILITARY MODEL MUSTARD POISONING REMOVAL SKIN SOMAN STUDY SULPHUR SULPHUR MUSTARD TOPICAL toxic TREATMENT VX Warfare 2/20/2017Previous studies have demonstrated that haemostatic products with an absorptive mechanism of action retain their clotting efficiency in the presence of toxic materials and are effective in decontaminating chemical warfare (CW) agents when applied to normal, intact skin. The purpose of this in vitro study was to assess three candidate haemostatic products for effectiveness in the decontamination of superficially damaged porcine skin exposed to the radiolabelled CW agents, soman (GD), VX and sulphur mustard (HD). Controlled physical damage (removal of the upper 100 mum skin layer) resulted in a significant enhancement of the dermal absorption of all three CW agents. Of the haemostatic products assessed, WoundStat was consistently the most effective, being equivalent in performance to a standard military decontaminant (fuller's earth). These data suggest that judicious application of haemostatic products to wounds contaminated with CW agents may be a viable option for the clinical management of casualties presenting with contaminated, haemorrhaging injuries. Further studies using a relevant animal model are required to confirm the potential clinical efficacy of WoundStat for treating wounds contaminated with CW agents. Copyright (c) 2017 John Wiley & Sons, Ltd121036" field[33]: Not in File?PMa, K.W. Chok, K.S. Chan, C.K. Dai, W.C. Sin, S.L. Lau, F.L. Chan, S.C. Lo, C.M.2017TLiver transplantation: a life-saving procedure following amatoxin mushroom poisoning93-96Hong Kong Medical Journal231Abdomen ACUTE acute liver failure acute poisoning ALANINE AMANITA MUSHROOMS AMMONIA Bilirubin BLOOD case CASE REPORT case reports Case-report CLINICAL College computed tomography CREATININE DONOR Emergencies emergency EMERGENCY DEPARTMENT FAILURE Fever GASTROENTERITIS HEPATOTOXICITY HI HOSPITAL Immunosuppression INFORMATION INGESTION INR INTENSIVE CARE intensive care unit LIVER Liver failure LIVER FUNCTION LIVER NECROSIS LIVER TRANSPLANT Liver Transplantation Man MUSHROOM N-ACETYLCYSTEINE NAC NECROSIS NO PATIENT PENICILLIN Poison POISONING POSTOPERATIVE recovery SERUM SILIBININ SYMPTOMS TEST TOMOGRAPHY TRANSPLANT TREATMENT UNIT vitamin VITAMIN K2/2017120884%<RefMgr field[33]: Not in File?(Madah-Amiri, D. Clausen, T. Lobmaier, P.2017LRapid widespread distribution of intranasal naloxone for overdose prevention17-23Drug and Alcohol Dependence173ANTAGONIST As Benzodiazepine DEATH Deaths DISTRIBUTION FACILITIES HOME Injecting INTRANASAL MET method methods NALOXONE OPIOID Opioid overdose Opioids OVERDOSE Population PREVENTION QUESTIONNAIRE RISK STUDY Time use Volume 1/28/2017BACKGROUND: Take home naloxone programs have been successful internationally in training bystanders to reverse an opioid overdose with naloxone, an opioid antagonist. A multi-site naloxone distribution program began in Norway in 2014 as part of a national overdose prevention strategy. The aim of this study was to a) describe the program, and b) present findings from the government-supported intervention. METHODS: From July 2014 to December 2015, staff from multiple low-threshold facilities trained clients on how to use intranasal naloxone. Distribution occurred without an individual prescription or physician present. Questionnaires from initial and refill trainings were obtained, and distribution rates were monitored. RESULTS: There were 2056 naloxone sprays distributed from one of the 20 participating facilities, with 277 reports of successful reversals. Participants exhibited known risks for overdosing, with injecting (p=0.02, OR=2.4, 95% CI=1.14, 5.00) and concomitant benzodiazepine use (p=0.01, OR=2.6, 95% CI=1.31, 5.23) being significant predictors for having had high rates of previous overdoses. Suggested target coverage for large-scale programs was met, with an annual naloxone distribution rate of 144 per 100,000 population, as well as 12 times the cities mean annual number of opioid-related deaths. CONCLUSION: A government-supported multisite naloxone initiative appears to achieve rapid, high volume distribution of naloxone to an at-risk population1208712 field[33]: Not in File?J-Mahajan, A. Tandon, V.R. Sharma, R. Singh, D.2012%Organochlorine (endosulfan) poisoning102-104 JK Science142>Agriculture ANTIDOTE As BLOOD BRAIN case central nervous system CYCLODIENE DATA DEATH DRUG drugs edema ENDOSULFAN HUMAN Humans hypoglycemia INTENSIVE CARE intensive care unit IS KIDNEY LEAD LIVER MORBIDITY NO oc ORGANOCHLORINE OXIDATIVE STRESS PAM Poison POISONING seizure SEIZURES STRESS suicidal TREATMENT UNIT UNITS2012120842V Not in File*?Mahajan, S. Shah, J.2016gA mixed toxidrome presenting with bilateral ptosis with normal pupils: the first case in the literature682-684+Journal of Family Medicine and Primary Care53 ADULT As case CASE REPORT Case-report Combined toxicity DIAGNOSIS Diarrhea ENVIRONMENTAL family HAZARD IS JATROPHA JATROPHA CURCAS MORBIDITY MORTALITY neurotoxic NEUROTOXICITY NO PATIENT Pupil snake bite SNAKEBITE SYMPTOMS Toxicities TOXICITY TREATMENT use Vomiting WHO7/2016$Snakebite is an environmental hazard associated with a significant morbidity and mortality. Two main types of toxicity occur due to snakebite, namely vasculotoxicity and neurotoxicity. Neurotoxic snakebites present mainly with bilateral ptosis with dilated pupils and/or difficulty in breathing. Jatropha curcas belongs to the family Euphorbiaceae and is commonly referred to as "Ratanjyot" in Gujarati. It has got many medicinal uses such as anticancerous properties and bio-oil. There are very few cases of its toxicity in adults. Toxicity from it causes meiosis, vomiting, diarrhea, etc., We will hereby discuss one such patient who consumed J. curcas seeds intentionally, became drowsy and accidentally got bit by a snake, and then, the patient started having bilateral ptosis, but with normal-sized pupils. There is no case reported yet in the literature mentioning the combined toxicity of snakebite and J. curcas, so we thought to publish this first case report of its kind in the world, thus discussing its diagnosis, symptoms, and treatment modalities121045- field[33]: Not in File ?J}Mamakwa, S. Kahan, M. Kanate, D. Kirlew, M. Folk, D. Cirone, S. Rea, S. Parsons, P. Edwards, C. Gordon, J. Main, F. Kelly, L.2017xEvaluation of 6 remote First Nations community-based buprenorphine programs in northwestern Ontario: Retrospective study137-145Canadian Family Physician632KADDICTION As BUPRENORPHINE Cohort Cohort studies Cohort study DRUG EVALUATION healing IS Long term Long-term maintenance maintenance treatment METHADONE method OPIOID opioid addiction opioid dependence Opioids outcome PATIENT Population recovery Retrospective study SCREENING STRESS STUDY Testing THERAPY TRAUMA TREATMENT URINE use2/2017OBJECTIVE: To evaluate established opioid addiction treatment programs that use traditional healing in combination with buprenorphine-naloxone maintenance treatment in 6 First Nations communities in the Sioux Lookout region of northwestern Ontario. DESIGN: Retrospective cohort study. SETTING: Six First Nations communities in northwestern Ontario. PARTICIPANTS: A total of 526 First Nations participants in opioid-dependence treatment programs. INTERVENTION: Buprenorphine-naloxone substitution therapy and First Nations healing programming. MAIN OUTCOME MEASURES: Retention rates and urine drug screening (UDS) results. RESULTS: Treatment retention rates at 6, 12, and 18 months were 84%, 78%, and 72%, respectively. We estimate that the rate at 24 months will also be more than 70%. The UDS programming varied and was implemented in only 1 community. Initially urine testing was voluntary and it then became mandatory. Screening with either method found the proportion of urine samples with negative results for illicit opioids ranged between 84% and 95%. CONCLUSION: The program's treatment retention rates and negative UDS results were higher than those reported for most methadone and buprenorphine-naloxone programs, despite a patient population where severe posttraumatic stress disorder is endemic, and despite the programs' lack of resources and addiction expertise. Community-based programs like these overcome the initial challenge of cultural competence. First Nations communities in other provinces should establish their own buprenorphinenaloxone programs, using local primary care physicians as prescribers. Sustainable core funding is needed for programming, long-term aftercare, and trauma recovery for such initiatives120958' Not in File B?'Manasfi, T. Coulomb, B. Boudenne, J.-L.2017fOccurrence, origin, and toxicity of disinfection byproducts in chlorinated swimming pools: an overview9International Journal of Hygiene and Environmental early: doi: 10.1016/j.ijheh.2017.01.005not published, 28 Feb 17@ACID Adverse ADVERSE EFFECTS ANIMAL As ASSESSMENT Association BLADDER Bladder cancer CANCER carcinogenic chemical CHEMISTRY CHLORINATED CHLORINE Content DATA DBPs DISINFECTANT disinfectants Disinfection byproducts epidemiologic EXPOSURE genotoxic HAIR HALOACETONITRILES HEALTH Health effects HUMAN Humans INFECTION Infections INORGANIC IS neurotoxic NITROSAMINES Occurrence ORGANIC personal care products Potency PRECURSOR quality REACTIONS RESPIRATORY REVIEW RISK RISK ASSESSMENT Route SKIN STUDY SWEAT SWIMMING POOLS Toxicities TOXICITY TREATMENT TRIHALOMETHANES URINE WATER 1/30/2017WDisinfection treatments are critical to conserve the microbiological quality of swimming pool water and to prevent water-borne infections. The formation of disinfection byproducts (DBPs) in swimming pools is an undesirable consequence resulting from reactions of disinfectants (e.g. chlorine) with organic and inorganic matter present in pool water, mainly brought by bathers. A considerable body of occurrence studies has identified several classes of DBPs in swimming pools with more than 100 compounds detected, mainly in chlorinated freshwater pools. Trihalomethanes (THMs), haloacetic acids (HAAs), haloacetaldehydes (HALs) are among the major DBPs in swimming pools. Other DBPs such as haloacetonitriles (HAN), haloamines, nitrosamines, and halobenzoquinones have also been detected. Researchers have been interested in identifying the precursors responsible for the formation of DBPs. In swimming pools, anthropogenic organic loads brought by swimmers increase the complexity of pool water chemistry. When human inputs (e.g. sweat, urine, hair, skin and personal care products) containing very diverse organic compounds are introduced to pools by swimmers, they react with chlorine resulting in the formation of complex mixtures of DBPs. The overwhelming majority of the total organic halide (TOX) content is still unknown in swimming pools. Exposure of swimmers to DBPs can take place through multiple routes, depending on the chemical properties of each DBP. Toxicological studies have shown that swimming pool water can be mutagenic with different potencies reported in different studies. Many DBPs have been shown to be genotoxic and carcinogenic. DBPs were also shown to induce reproductive and neurotoxic adverse effects in animal studies. Epidemiologic studies in humans have shown that exposure to DBPs increases the risk of respiratory adverse effects and bladder cancer. Association between DBPs and other health effects are still inconclusive. Data gathered in the present review (occurrence, toxicity, and toxicological reference values) could be used in conducting chemical risk assessment studies in swimming pools120889- field[33]: Not in File"U?JcManchikanti, L. Kaye, A.M. Knezevic, N.N. McAnally, H. Slavin, K. Trescot, A.M. Blank, S. Pampati, V. Abdi, S. Grider, J.S. Kaye, A.D. Manchikanti, K.N. Cordner, H. Gharibo, C.G. Harned, M.E. Albers, S.L. Atluri, S. Aydin, S.M. Bakshi, S. Barkin, R.L. Benyamin, R.M. Boswell, M.V. Buenaventura, R.M. Calodney, A.K. Cedeno, D.L. Datta, S. Deer, T.R. Fellows, B. Galan, V. Grami, V. Hansen, H. Helm, S., II Justiz, R. Koyyalagunta, D. Malla, Y. Navani, A. Nouri, K.H. Pasupuleti, R. Sehgal, N. Silverman, S.M. Simopoulos, T.T. Singh, V. Solanki, D.R. Staats, P.S. Vallejo, R. Wargo, B.W. Watanabe, A. Hirsch, J.A.2017Responsible, safe, and effective prescription of opioids for chronic non-cancer pain: American Society of Interventional Pain Physicians (ASIPP) guidelinesS3-S92Pain Physician202SABUSE adherence Adverse As ASSESSMENT CHRONIC chronic pain CLINICAL CONSTIPATION DATA DEATH Deaths Decision making Development DIAGNOSIS discontinuation dose DRUG DRUG ABUSE Drug testing drugs effectiveness EFFICACY ELECTROCARDIOGRAM EPIDEMIC evidence FAILURE FDA FENTANYL Guidelines HEROIN Imaging IS Long term Long-term Low doses MANAGEMENT METHADONE method methods MONITORING MORPHINE OPIOID Opioid abuse Opioids outcome pain PATIENT PDMP PRESCRIBING Prescription drug abuse prescription drug monitoring PSYCHOLOGICAL quality Quality of life Regulation REGULATIONS RESEARCH REVIEW RISK safe SCALE scientific evidence SCREENING Side effect side effects side-effects Stability standards STATUS SUBSTANCE ABUSE Synthesis Testing THERAPY TREATMENT TRIAL URINE US use WHO2/2017[BACKGROUND: Opioid use, abuse, and adverse consequences, including death, have escalated at an alarming rate since the 1990s. In an attempt to control opioid abuse, numerous regulations and guidelines for responsible opioid prescribing have been developed by various organizations. However, the US opioid epidemic is continuing and drug dose deaths tripled during 1999 to 2015. Recent data show a continuing increase in deaths due to natural and semisynthetic opioids, a decline in methadone deaths, and an explosive increase in the rates of deaths involving other opioids, specifically heroin and illicit synthetic fentanyl. Contrary to scientific evidence of efficacy and negative recommendations, a significant proportion of physicians and patients (92%) believe that opioids reduce pain and a smaller proportion (57%) report better quality of life. In preparation of the current guidelines, we have focused on the means to reduce the abuse and diversion of opioids without jeopardizing access for those patients suffering from non-cancer pain who have an appropriate medical indication for opioid use. OBJECTIVES: To provide guidance for the prescription of opioids for the management of chronic non-cancer pain, to develop a consistent philosophy among the many diverse groups with an interest in opioid use as to how appropriately prescribe opioids, to improve the treatment of chronic non-cancer pain and to reduce the likelihood of drug abuse and diversion. These guidelines are intended to provide a systematic and standardized approach to this complex and difficult arena of practice, while recognizing that every clinical situation is unique. METHODS: The methodology utilized included the development of objectives and key questions. The methodology also utilized trustworthy standards, appropriate disclosures of conflicts of interest, as well as a panel of experts from various specialties and groups. The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed, with a best evidence synthesis of the available literature, and utilized grading for recommendation as described by the Agency for Healthcare Research and Quality (AHRQ).Summary of Recommendations:i. Initial Steps of Opioid Therapy 1. Comprehensive assessment and documentation. (Evidence: Level I; Strength of Recommendation: Strong) 2. Screening for opioid abuse to identify opioid abusers. (Evidence: Level II-III; Strength of Recommendation: Moderate) 3. Utilization of prescription drug monitoring programs (PDMPs). (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 4. Utilization of urine drug testing (UDT). (Evidence: Level II; Strength of Recommendation: Moderate) 5. Establish appropriate physical diagnosis and psychological diagnosis if available. (Evidence: Level I; Strength of Recommendation: Strong) 6. Consider appropriate imaging, physical diagnosis, and psychological status to collaborate with subjective complaints. (Evidence: Level III; Strength of Recommendation: Moderate) 7. Establish medical necessity based on average moderate to severe (>/= 4 on a scale of 0 - 10) pain and/or disability. (Evidence: Level II; Strength of Recommendation: Moderate) 8. Stratify patients based on risk. (Evidence: Level I-II; Strength of Recommendation: Moderate) 9. Establish treatment goals of opioid therapy with regard to pain relief and improvement in function. (Evidence: Level I-II; Strength of Recommendation: Moderate) 10. Obtain a robust opioid agreement, which is followed by all parties. (Evidence: Level III; Strength of Recommendation: Moderate)ii. Assessment of Effectiveness of Long-Term Opioid Therapy 11. Initiate opioid therapy with low dose, short-acting drugs, with appropriate monitoring. (Evidence: Level II; Strength of Recommendation: Moderate) 12. Consider up to 40 morphine milligram equivalent (MME) as low dose, 41 to 90 MME as a moderate dose, and greater than 91 MME as high dose. (Evidence: Level II; Strength of Recommendation: Moderate) 13. Avoid long-acting opioids for the initiation of opioid therapy. (Evidence: Level I; Strength of Recommendation: Strong) 14. Recommend methadone only for use after failure of other opioid therapy and only by clinicians with specific training in its risks and uses, within FDA recommended doses. (Evidence: Level I; Strength of Recommendation: Strong) 15. Understand and educate the patients of the effectiveness and adverse consequences. (Evidence: Level I; Strength of Recommendation: Strong) 16. Similar effectiveness for long-acting and short-acting opioids with increased adverse consequences of long-acting opioids. (Evidence: Level I-II; Strength of recommendation: Moderate to strong) 17. Periodically assess pain relief and/or functional status improvement of >/= 30% without adverse consequences. (Evidence: Level II; Strength of recommendation: Moderate) 18. Recommend long-acting or high dose opioids only in specific circumstances with severe intractable pain. (Evidence: Level I; Strength of Recommendation: Strong)iii. Monitoring for Adherence and Side Effects 19. Monitor for adherence, abuse, and noncompliance by UDT and PDMPs. (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 20. Monitor patients on methadone with an electrocardiogram periodically. (Evidence: Level I; Strength of Recommendation: Strong). 21. Monitor for side effects including constipation and manage them appropriately, including discontinuation of opioids when indicated. (Evidence: Level I; Strength of Recommendation: Strong)iv. Final Phase 22. May continue with monitoring with continued medical necessity, with appropriate outcomes. (Evidence: Level I-II; Strength of Recommendation: Moderate) 23. Discontinue opioid therapy for lack of response, adverse consequences, and abuse with rehabilitation. (Evidence: Level III; Strength of Recommendation: Moderate) CONCLUSIONS: These guidelines were developed based on comprehensive review of the literature, consensus among the panelists, in consonance with patient preferences, shared decision-making, and practice patterns with limited evidence, based on randomized controlled trials (RCTs) to improve pain and function in chronic non-cancer pain on a long-term basis. Consequently, chronic opioid therapy should be provided only to patients with proven medical necessity and stability with improvement in pain and function, independently or in conjunction with other modalities of treatments in low doses with appropriate adherence monitoring and understanding of adverse events.Key words: Chronic pain, persistent pain, non-cancer pain, controlled substances, substance abuse, prescription drug abuse, dependency, opioids, prescription monitoring, drug testing, adherence monitoring, diversionDisclaimer: The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."121084I Not in File B? Mandal, P.2017FMolecular insight of arsenic-induced carcinogenesis and its prevention.Naunyn-Schmiedeberg's Archives of Pharmacology,online early: doi: 10.1007/s00210-017-1351-xnot published, 01 Mar 17Affect agent AIR ANIMAL ANTIOXIDANT ARSENIC carcinogenesis CARDIOVASCULAR Cardiovascular disease Cardiovascular diseases CHELATING AGENTS CONTAMINATION DIETARY DISEASE DRINKING WATER Environment ENVIRONMENTAL EXPOSURE FOOD Groundwater Heavy metal HIGH LEVELS HUMAN India INDIUM IS LESIONS LEVELS MECHANISM METALS MITOCHONDRIA NEUROLOGICAL OXYGEN Population PREVENTION PROTEIN PSYCHOLOGICAL safe SKIN SOIL Source SPECIES TISSUE Toxicities TOXICITY WATER 2/22/2017/Population of India and Bangladesh and many other parts of the world are badly exposed to arsenic through drinking water. Due to non-availability of safe drinking water, they are dependent on arsenic-contaminated water. Generally, poverty level is high in those areas with lack of proper nutrition. Arsenic is considered to be an environmental contaminant and widely distributed in the environment due to its natural existence and anthropogenic applications. Contamination of arsenic in both human and animal could occur through air, soil, and other sources. Arsenic exposure mainly occurs in food materials through drinking water with high levels of arsenic in it. High levels of arsenic in groundwater have been found to be associated with various health-related problems including arsenicosis, skin lesions, cardiovascular diseases, reproductive problems, psychological, neurological, immunotoxic, and carcinogenesis. The mechanism of arsenic toxicity consists in its transformation in metaarsenite, which acylates protein sulfhydryl groups, affect on mitochondria by inhibiting succinic dehydrogenase activity and can uncouple oxidative phosphorylation with production of active oxygen species by tissues. A variety of dietary antioxidant supplements are useful to protect the carcinogenetic effects of arsenic. They play crucial role for counteracting oxidative damage and protect carcinogenesis by chelating with heavy metal moiety. Phytochemicals and chelating agents will be beneficial for combating heavy metal-induced carcinogenesis through its biopharmaceutical properties121076, field[33]: Not in File ?>Manini, A.F. Nair, A.P. Vedanthan, R. Vlahov, D. Hoffman, R.S.2017UValidation of the prognostic utility of the electrocardiogram for acute drug overdosee004320)Journal of the American Heart Association62ACETAMINOPHEN ACUTE ADULT Adverse Age ANAPHYLAXIS ARREST As Benzodiazepine BENZODIAZEPINES CARDIAC CARDIAC ARREST CARDIOTOXICITY CARDIOVASCULAR CHRONIC CLEARANCE Cohort Cohort studies Cohort study DATA DRUG drug overdose drug toxicity dysrhythmia ECG ELECTROCARDIOGRAM Emergencies emergency EMERGENCY DEPARTMENT EVALUATION EXPOSURE HOSPITAL injuries Injury IS LEAD MALE MET method methods OPIOID Opioids outcome OVERDOSE PATIENT Population PROGNOSIS QT QT prolongation r RISK SHOCK STUDY Toxicities TOXICITY Urban Validation WHO2/3/2017BACKGROUND: While it is certain that some emergency department patients with acute drug overdose suffer adverse cardiovascular events (ACVE), predicting ACVE is difficult. The prognostic utility of the ECG for heterogeneous drug overdose patients remains to be proven. This study was undertaken to validate previously derived features of the initial ECG associated with ACVE in this population. METHODS AND RESULTS: We performed a prospective validation cohort study to evaluate adult emergency department patients with acute drug overdose at 2 urban university hospitals over 5 years in whom an emergency department admission ECG was performed. Exclusion criteria were alternate diagnoses, anaphylaxis, chronic drug toxicity, and missing outcome data. ACVE was defined as any of the following: circulatory shock, myocardial injury, ventricular dysrhythmia, or cardiac arrest. Blinded cardiologists interpreted ECGs for previously derived predictors of ACVE (ectopy, QT prolongation, nonsinus rhythm, ischemia/infarction), QT dispersion, and prominent R wave in lead AVR. Of 589 patients who met inclusion criteria (48% male, mean age 42), there were 95 ACVEs (39 shock, 64 myocardial injury, 26 dysrhythmia, 16 cardiac arrest). The most common drug exposures were as follows: benzodiazepines, opioids, and acetaminophen. Previously derived criteria were highly predictive of ACVE, with QT correction >500 ms as the highest risk feature (OR 11.2, CI 4.6-27). CONCLUSIONS: This study confirms that early ECG evaluation is essential to assess the cardiovascular prognosis and medical clearance of emergency department patients with acute drug overdose. Furthermore, this study validates previously derived high-risk features of the admission ECG to risk stratify for ACVE in this patient population120740) field[33]: Not in File jB?SManseau, M.W. Rajparia, A. Joseph, A. Azarchi, S. Goff, D. Satodiya, R. Lewis, C.F.2017dClinical characteristics of synthetic cannabinoid use in a large urban psychiatric emergency settingSubstance Use and Misuse0online early: doi: 10.1080/10826084.2016.1263663not published, 16 Feb 17ACUTE Adverse adverse event Adverse events Agitation CANNABINOID cannabinoids CANNABIS case CASE REPORT case reports Case-report CLINICAL comorbid complications DATA DATABASE DESIGNER DRUGS DIAGNOSIS Emergencies emergency HOSPITAL IS MALE method methods NOVEL PSYCHOACTIVE SUBSTANCES Observation Poison Poison Control Centers Population PSYCHIATRIC PUBLIC SERVICE STUDY Substance use SYMPTOMS SYNTHETIC CANNABINOID Synthetic cannabinoids UNITED STATES Urban use WHO2/3/2017+BACKGROUND: Increasing reports of synthetic cannabinoid (SC)-related adverse events have largely comprised case reports and analyses of calls to poison control centers. Existing studies have also mostly involved white male populations. OBJECTIVES: The purpose of this study is to systematically describe clinical characteristics of SC use in a relatively large, diverse, urban sample presenting to a psychiatric emergency setting. METHODS: SC users (n = 110) were identified by reviewing charts (n = 948) from the psychiatric emergency service of a large, urban public hospital in the United States for November 2014, which was randomly selected from the 12 months of that year. Sociodemographic data were collected from administrative databases and clinical data were collected from the electronic medical record. RESULTS: SC users were mostly non-white (90.0%) males (95.5%), who were likely to be police-involved (34.5%) and homeless (84.5%). SC users also had significant and often pre-existing psychiatric and substance use comorbidity, including acute psychotic symptoms (70.0%), more than one comorbid psychiatric diagnosis (31.8%) and primary psychotic disorder diagnosis (40.0%), past psychiatric visits to the hospital (70.9%), comorbid substance use (62.7%), agitation requiring intervention (22.7%), and the need for extended psychiatric observation (15.5%) and inpatient admission (34.5%). Relatively limited medical complications were identified. Conclusions/Importance: In this sample, SC use affected a sociodemographically disadvantaged and mentally ill population, likely exacerbating existing psychiatric problems. This is one of the only studies to systematically examine the clinical effects of SC use in a significant clinical sample, and the first study in an urban, racial/ethnic minority, and vulnerable sample120738/ field[33]: Not in File ?uMar, F. Crowther, M. Gold, A. Lu, G. Leeds, J. Wiens, B. Mathur, V. Castillo, J. Conley, P. Connolly, S. Curnutte, J.2016Andexanet alfa: an investigational universal antidote for reversal of anticoagulation of factor Xa inhibitors in healthy human volunteers170-Abstract only Direct FXa inhibitors have demonstrated convincing anticoagulant efficacy. However, risk of major bleeding is a concern and no specific antidotes are available for reversal. Andexanet alfa (AnXa), a recombinant modified FXa, is an investigational specific antidote for FXa inhibitors. We report data from the ANNEXA"! Phase 3 registration studies in older healthy subjects anticoagulated with apixaban (apix) or rivaroxaban (riva).ANNEXA A&R were 2 phase 3, randomized, double-blind, placebo-controlled studies of AnXa in healthy subjects age 50 to 75 administered either apixaban or rivaroxaban. Andexanet dose selection was based on phase 2 data and PK/PD modeling, which will be presented. In ANNEXA"!-A, subjects were treated with apix 5 mg twice daily for 4 days to achieve steady-state concentrations. AnXa (Part 1: 400 mg bolus; Part 2: 400 mg bolus plus 4 mg/min × 2-hour infusion) or placebo was administered on day 4, 3 hours after the last apix dose. In ANNEXA"!-R, subjects were treated with riva 20 mg every day for 4 days to achieve steady-state concentrations. AnXa (part 1: 800 mg bolus; part 2: 800 mg bolus plus 8 mg/min × 2-hour infusion) or placebo was administered on day 4, 4 hours after the last riva dose. Safety data were collected through day 43.ANNEXA-A&R enrolled 63 and 82 subjects, respectively. The primary efficacy end point, percent change from baseline in anti-FXa activity to nadir (part 1: between 2 and 5 minutes postbolus; part 2: between 10 minutes before and 5 minutes after the end of the continuous infusion) was met for each part with high statistical significance (P < .001 vs placebo). Additional efficacy end points, including reduction in plasma free inhibitor concentration and restoration of thrombin generation, were also met. There were no serious adverse events, thrombotic events, or antibodies to FX or FXa. The andexanet PK/PD model accurately predicted the riva and apix anti-FXa activity observed in this study.ANNEXA-A&R achieved all primary and secondary end points with high statistical significance. AnXa treatment resulted in rapid and sustained reversal of both apix- and riva-induced anticoagulation. A phase 3b/4 confirmatory study (ANNEXA-4) in patients with acute major bleeds is ongoing. Neurosurgery63 CN_suppl_1OANTICOAGULANT anticoagulants anticoagulation ANTIDOTE Antidotes HUMAN VOLUNTEER8/1/20161209114 field[33]: Not in File B?Marie, I. Gehanno, J.-F. Bubenheim, M. Duval-Modeste, A.-B. Joly, P. Dominique, S. Bravard, P. Noël, D. Cailleux, A.-F. Weber, J. Lagoutte, P. Benichou, J. Levesque, H. Goullé, J.-P.2017fSystemic sclerosis and exposure to heavy metals: a case control study of 100 patients and 300 controlsAutoimmunity Reviews/online early: doi: 10.1016/j.autrev.2017.01.004not published, 16 Feb 17Age ANTIMONY Association CADMIUM case case-control DETECTION Development DIAGNOSIS EXPOSURE FEMALE Gender HAIR Heavy metal HEAVY METALS impact Inductively coupled plasma mass LEAD LEVELS MALE MASS SPECTROMETRY MERCURY METALS method methods MOLYBDENUM OCCUPATIONAL OCCUPATIONAL EXPOSURE PALLADIUM PATIENT PLASMA PLATINUM quantification RISK Risk factor RISK FACTORS SCLEROSIS SMOKING SPECTROMETRY STUDY SYSTEMIC ZINC 1/27/2017OBJECTIVE: This case control study assessed: the relationship of systemic sclerosis (SSc) related to exposure to heavy metals, the risk of SSc related to occupational exposure in male and female patients. METHODS: From 2005 to 2008, 100 patients with a definite diagnosis of SSc were included in the study; 3 age, gender, and smoking habits matched controls were selected for each patient. All SSc patients and controls underwent detection and quantification of heavy metal traces in hair samples, using multi-element inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: SSc patients exhibited higher median levels of the following metals: antimony (p=0.001), cadmium (p=0.0003), lead (p=0.02), mercury (p=0.02), molybdenum (p=0.04), palladium (p<0.001) and zinc (p=0.0003). A marked association between SSc and occupational exposure was further found for: 1) antimony (p=0.008) and platinum (p=0.04) in male patients; and 2) antimony (p=0.02), cadmium (p=0.001), lead (p=0.03), mercury (p=0.03), palladium (p=0.0003) and zinc (p=0.0001) in female patients CONCLUSION: The results show the impact of occupational risk factors in the development of SSc for: antimony, cadmium, lead, mercury, molybdenum, palladium and zinc. Thus, occupational exposure should be systematically checked in all SSc patients at diagnosis. Finally, the association between SSc and occupational exposure may be variable according to patients" gender120700. field[33]: Not in File ?PMarques Gomes, A.C.N. Nabhani-Gebara, S. Kayyali, R. Buonocore, F. Calabrese, G.2016NSurvey of community pharmacists' perception of electronic cigarettes in Londone013214BMJ Open611dAdverse ADVERSE EFFECTS As CIGARETTE Cigarettes Content Cough Development DOSAGE E CIGARETTE E Cigarettes E-CIGARETTE e-Cigarettes e-liquid effectiveness EFFICACY ELECTRONIC CIGARETTE Electronic cigarettes Electronic-cigarette Guidelines INFORMATION INTERNET Mouth NICOTINE NO Pathway Regulation REGULATIONS RESPONSE RATE SAFETY SMOKING SURVEY toxic UK use 11/10/2016,OBJECTIVES: To seek community pharmacists' perception on use, safety and possible effectiveness of e-cigarettes as quit smoking tools, and their future regulation. SETTING: A survey of a sample of 154 community pharmacies across London, UK. CONTEXT: E-cigarettes have exclusively established themselves in the market through consumers-led demand. To date, e-cigarettes still remain unregulated and can be easily purchased in shops, over the internet, but more controversially also in pharmacies in the UK. Pharmacists find themselves with a shortage of information on their safety and efficacy, and may experience an ethical dilemma when consulted by patients/customers. KEY FINDINGS: Response rate: 60% (n=92). Independent pharmacies accounted for 90% of the sample. The majority of participants (73%) sell e-cigarettes. A minority of participants (20%) have been presented with adverse effects such as cough and dry mouth. As possible reasons for their use, pharmacists ranked 'aid in stop smoking' as the most important (56%), with 'cheaper alternative' (43%) and 'social/recreational use' (31%) being the least important ones. Safety issues were raised as statements such as 'e-liquid in cartridges may be toxic' were agreed by 52% of respondents. The majority of pharmacists (97%) were supportive of e-cigarettes being regulated, expressing current concerns regarding excipients (42%) and nicotine content (34%). Participants indicated that they would require training in the form of information packs (88%), online tutorials (67%), continuous professional development (CPD) workshops (43%) to cover safety, counselling, dosage instructions, adverse effects and role in the smoking cessation care pathway in the future. CONCLUSIONS: Pharmacists expressed concerns about the safety of e-cigarettes, especially regarding the amounts of excipients and nicotine as these still remain unregulated. Currently, there are no guidelines for pharmacists regarding e-cigarettes. Community pharmacists look forward to regulations so to conduct their duties in a more confident and legislated fashion120859- field[33]: Not in FileWB?Marsden, J. Stillwell, G. Jones, H. Cooper, A. Eastwood, B. Farrell, M. Lowden, T. Maddalena, N. Metcalfe, C. Shaw, J. Hickman, M.2017Does exposure to opioid substitution treatment in prison reduce the risk of death after release? A national prospective observational study in England Addiction$online early: doi: 10.1111/add.13779not published, 16 Feb 17ACUTE ADULT Age ALCOHOL Alcohol use All-cause mortality As Benzodiazepine BENZODIAZEPINES COCAINE Cohort Cohort studies Cohort study DEATH Deaths DOE dose DRUG EXPOSURE FATAL FEMALE FOLLOW UP Follow-up HAZARD Injecting maintenance MALE Measurement MISUSE MODEL MORTALITY NO Odds Ratio OPIOID opioid use disorder Opioids outcome OVERDOSE POISONING py Reduction Release RISK Risk factor RISK FACTORS Sex STUDY THERAPY TREATMENT use2/4/2017 BACKGROUND AND AIMS: People with opioid use disorder (OUD) in prison face an acute risk of death after release. We estimated whether prison-based opioid substitution treatment (OST) reduces this risk. DESIGN: Prospective observational cohort study using prison healthcare, national community drug misuse treatment and deaths registers. SETTING: Recruitment at 39 adult prisons in England (32 male; 7 female) accounting for 95% of OST treatment in England during study planning. PARTICIPANTS: Adult prisoners diagnosed with OUD (recruited: September 2010 to August 2013; first release: September 2010; last release: October 2014; follow-up to February 2016; n = 15,141 in the risk set). INTERVENTION AND COMPARATOR At release, participants were classified as OST exposed (n = 8,645) or OST unexposed (n = 6,496). The OST unexposed group did not receive OST, or had been withdrawn, or had a low dose. MEASUREMENTS: Primary outcome: all-cause mortality (ACM) in the first 4 weeks. SECONDARY OUTCOMES: drug-related poisoning (DRP) deaths in the first 4 weeks; ACM and DRP mortality after 4 weeks to 1 year; admission to community drug misuse treatment in the first 4 weeks. Unadjusted and adjusted cox regression models (covariates: sex, age, drug injecting, problem alcohol use, use of benzodiazepines, cocaine, prison transfer and admission to community treatment), tested difference in mortality rates and community treatment uptake. FINDINGS: In the first 4 weeks after prison release, there were 24 ACM deaths: 6 in the OST exposed group and 18 in the OST unexposed group (mortality rate 0.93 per 100 person years [PY] versus 3.67 per 100 PY; Hazard Ratio [HR] 0.25; 95% Confidence interval [CI] 0.10 to 0.64). There were 18 DRP deaths: OST exposed group mortality rate 0.47 per 100 PY versus 3.06 per 100 PY in the OST unexposed group (HR 0.15; 95% CI 0.04 to 0.53). There was no group difference in mortality risk after the first month. The OST exposed group was more likely to enter drug misuse treatment in the first month post-release (odds ratio 2.47, 95% CI 2.31 to 2.65). The OST mortality protective effect on ACM and DRP mortality risk was not attenuated by demographic, overdose risk factors, prison transfer or community treatment (fully adjusted HR 0.25; 95% CI 0.09 to 0.64 and HR 0.15; 95% CI 0.04 to 0.52, respectively). CONCLUSIONS: In an English national study, prison-based opioid substitution therapy was associated with a 75% reduction in all-cause mortality and an 85% reduction in fatal drug-related poisoning in the first month after release120689# field[33]: Not in File h?Martínez-Peña, A.A. Rivera-Baños, J. Méndez-Carrillo, L.L. Ramírez-Solano, M.I. Galindo-Bustamante, A. Páez-Franco, J.C. Morimoto, S. González-Mariscal, L. Cruz, M.E. Mendoza-Rodríguez, C.A.2017Perinatal administration of bisphenol A alters the expression of tight junction proteins in the uterus and reduces the implantation rate106-120Reproductive Toxicology69Age ANIMAL Animals Bisphenol A BISPHENOL-A CELL DEVELOPMENTAL ESTRADIOL FEMALE FERTILITY Gestational LACTATION LEVELS NO PERINATAL PREGNANCY PROGESTERONE PROTEIN proteins RAT rats SERUM tight junction proteins TREATMENT UTERUS Vehicle 2/17/2017We studied the effect of bisphenol-A (BPA) administration to rats, during the perinatal period, on the fertility of F1 generation and on the expression of tight junction (TJ) proteins in the uterus during early pregnancy. Pregnant Wistar dams (F0) received: BPA-L (0.05mg/kg/day), BPA-H (20mg/kg/day) or vehicle, from gestational day (GD) 6 to lactation day 21. F1 female pups were mated at 3 months of age and sacrificed at GD 1, 3, 6, and 7. Serum hormonal levels, ovulation rate, number of implantation sites and expression of TJ proteins in the uterus of F1 females were evaluated. BPA treatment induced no change in ovulation rate, but induced alterations in progesterone (P4) and estradiol (E2) serum levels, and in implantation rate. With regards to TJ proteins, BPA-H increased claudin-1 during all GDs; eliminated the peaks of claudins -3 and -4 at GD 3 and 6, respectively; and decreased claudin-7 at GD 6, ZO-1 from GD 1-6, and claudin-3 at GD 7 in stromal cells. BPA-L instead, eliminated claudin-3 peak at GD 3, increased claudin-4 and decreased claudin-7 from GD 1-6, decreased claudin-1 at GD 3 and 7 and claudin-4 at GD 7 in stromal cells. BPA-L also decreased ZO-1 at GDs 1 and 3 and increased ZO-1 at GD 6. Thus, BPA treatment during perinatal period perturbed, when the animals reached adulthood and became pregnant, the particular expression of TJ proteins in the uterine epithelium and reduced in consequence the number of implantation sites1211080 field[33]: Not in File!?-Mary Fonseka, T. McKinley, G.P. Kennedy, S.H.2017XIs tetraethyl lead poison affecting contemporary indigenous suicides in Ontario, Canada?253-254Psychiatry Research251As Canada EPIDEMIC GASOLINE IS LEAD Lead Poisoning outbreak Poison POISONING Population PRECURSOR PROTEIN RISK Risk factor SNIFFING SUICIDE TETRAETHYL LEAD1/7/2017Prior to the mid-1980s, suicide in Indigenous population in Northwestern Ontario, Canada, was rare, occurring at rates of 1-2 per year among over 20 communities. By the early 1990s, the completed suicide rates in the same communities were among the highest in the world. Prior to the outbreak of the suicide epidemic, sniffing of gasoline containing tetraethyl was common in many communities. Existing literature confirms that tetraethyl lead poisoning is associated with alterations to the amyloid-beta protein precursor and amyloid-beta as well as the 5-HT-1B receptor. The presence of this risk factor within the population warrants further inquiry1210950 field[33]: Not in File B?Mazaud, C. Fardet, L.2017Relative risk of and determinants for adverse events of methotrexate prescribed at a low dose: a systematic review and meta-analysis of randomized, placebo-controlled trialsBritish Journal of Dermatology$online early: doi: 10.1111/bjd.15377not published, 28 Feb 17Abdominal Pain ACID Adverse adverse event Adverse events As DATA DATABASE DEATH dose duration EVIDENCE-BASED EXPOSURE Hand INJECTION INTRAMUSCULAR IS LEUCOPENIA LEVELS MEDLINE Meta-analysis METHOTREXATE pain PLACEBO REVIEW RISK STUDY systematic review TREATMENT TRIAL WITHDRAWAL2/9/2017XLow-dose (i.e., "Mazumdar, I. Goswami, K. Ali, M.S.2017Status of serum calcium, vitamin D and parathyroid hormone and hematological indices among lead exposed jewelry workers in Dhaka, Bangladesh110-116'Indian Journal of Clinical Biochemistry321ABSORPTION Affect ALBUMIN As BASE biological biosynthesis BLOOD BONE CALCIUM duration ENZYME ERYTHROCYTE ERYTHROPOIETIN EXPOSURE GASTROINTESTINAL GERMAN Hand HAZARD HEALTH Health hazard health hazards Heavy metal HEAVY METALS heme hemoglobin Hemoglobin synthesis HIGH LEVELS HORMONE Inhibition IS LEAD Lead exposure LEVELS METABOLISM METALS NEPHROTOXICITY OCCUPATIONAL PARATHYROID PARATHYROID HORMONE PROTEIN Release RENAL SERUM SILVER SOFT TISSUE STATUS STUDY Synthesis TISSUE URINE vitamin VITAMIN D VITAMIN D3 workers3/2017Jewelry utilizes lead either directly or as a base metal. Costume jewelry requires lead before molding and plating the product with valuable metals. Therefore, such ornaments have a great potential to release heavy metals having health hazards. Also, jewelry makers engaged in preparing German silver, an alloy, apply lead in smelting, alloying, rolling and milling silver wires and pieces. The metal is taken up by blood, soft tissues and bone. The biological effects of lead are dependent upon the level and duration of exposure. Lead inhibits three enzymes of heme biosynthesis- delta-amino-levulinic-acid dehydratase (ALAD), coproporphyrin oxidase, and ferrochelatase, impairing heme synthesis and depressing serum level of erythropoietin resulting in decreased hemoglobin synthesis. Lead exposure also affects calcium metabolism and impair the synthesis of Calcitriol. In the present study, jewelry makers from Dhaka, Bangladesh, were shown to have significantly high levels of lead, protein, albumin, and parathormone in their blood, and significantly high amount of zinc-protoporphyrin and delta-amino-levulinic-acid in their urine. The control group, on the other hand showed significantly higher amounts of calcium (both total and ionized form) Vitamin D3 and non-activated erythrocyte ALAD in their blood, along with hemoglobin. It might be due to inhibition of 1-alpha-hydroxylase enzyme in renal tubules. Lead causes nephro-toxicity and inhibits 1-alpha- hydroxylase enzyme leading to decreased calcitriol synthesis resulting in impaired calcium absorption across gastro-intestinal tract and renal tubules. Low Vitamin D3 and significantly increased Parathyroid hormone (PTH) in study group has been found120733+ field[33]: Not in File?+Mbughuni, M.M. Jannetto, P.J. Langman, L.J.2016-Mass spectrometry applications for toxicology272-287EJIFCC274analysis ANALYTICAL As CHROMATOGRAPHY CLINICAL Development DRUG drugs ENVIRONMENTAL FORENSIC Forensic toxicology GA GAS GAS CHROMATOGRAPHY GC-MS IS Laboratories LABORATORY LC-MS Liquid chromatography MASS SPECTROMETRY MECHANISM Mechanisms Mechanisms of action METABOLITE Metabolites PLASMA Poison Qualitative REVIEW SPECTROMETRY STUDY Tandem Mass Spectrometry TECHNIQUE toxic toxic effects TOXICOLOGY TREATMENT12/2016lToxicology is a multidisciplinary study of poisons, aimed to correlate the quantitative and qualitative relationships between poisons and their physiological and behavioural effects in living systems. Other key aspects of toxicology focus on elucidation of the mechanisms of action of poisons and development of remedies and treatment plans for associated toxic effects. In these endeavours, Mass spectrometry (MS) has become a powerful analytical technique with a wide range of application used in the Toxicological analysis of drugs, poisons, and metabolites of both. To date, MS applications have permeated all fields of toxicology which include; environmental, clinical, and forensic toxicology. While many different analytical applications are used in these fields, MS and its hyphenated applications such as; gas chromatography MS (GC-MS), liquid chromatography MS (LC-MS), inductively coupled plasma ionization MS (ICP-MS), tandem mass spectrometry (MS/MS and MSn) have emerged as powerful tools used in toxicology laboratories. This review will focus on these hyphenated MS technologies and their applications for toxicology120745+ field[33]: Not in FileJ?,McCall Jones, C. Baldwin, G.T. Compton, W.M.2017KRecent increases in cocaine-related overdose deaths and the role of opioids430-432!American Journal of Public Health1073COCAINE DATA DEATH Deaths DRIVING DRUG drug overdose FENTANYL HEROIN method methods OPIOID Opioids OVERDOSE Population STATISTICS Synthetic Opioid trends UNITED STATES use3/2017OBJECTIVES: To assess trends in cocaine overdose deaths and examine the role opioids play in these deaths. METHODS: We used data on drug overdose deaths in the United States from 2000 to 2015 collected in the National Vital Statistics System to calculate annual rates and numbers of cocaine-related overdose deaths overall and deaths both involving and not involving opioids. We assessed statistically significant changes in trends with joinpoint regression. RESULTS: Rates of cocaine-related overdose deaths increased significantly from 1.26 to 2.50 per 100 000 population from 2000 to 2006, declined to 1.35 in 2010, and increased to 2.13 in 2015. Cocaine-related overdose deaths involving opioids increased from 0.37 to 0.91 from 2000 to 2006, declined to 0.57 in 2010, and then increased to 1.36 in 2015. Cocaine-related overdose deaths not involving opioids increased from 0.89 to 1.59 from 2000 to 2006 and then declined to 0.78 in 2015. CONCLUSIONS: Opioids, primarily heroin and synthetic opioids, have been driving the recent increase in cocaine-related overdose deaths. This corresponds to the growing supply and use of heroin and illicitly manufactured fentanyl in the United States120853* field[33]: Not in FileiB?\McCracken, J.M. Chalise, P. Briley, S.M. Dennis, K.L. Jiang, L. Duncan, F.E. Pritchard, M.T.2017C57BL/6 substrains exhibit different responses to acute carbon tetrachloride exposure: Implications for work involving transgenic miceGene Expression+online early: doi: 10.3727/105221617X695050not published, 01 Mar 17ACUTE biological carbon CARBON TETRACHLORIDE CELL DATA DISEASE EXPERIMENTAL EXPOSURE HEPATIC HUMAN injuries Injury IS Laboratories LABORATORY LIVER liver injury MACROPHAGE macrophages METABOLISM MICE MODEL mouse NO STUDY2/9/2017Biological differences exist between strains of laboratory mice, and it is becoming increasingly evident that there aredifferences between substrains. In the C57BL/6 mouse, the primary substrains are called 6J and 6N. Previous studies have demonstrated that 6J and 6N mice differ in response to many experimental models of human disease. The aim of our study was to determine if differences exist between 6J and 6N mice in terms of their response to acute carbon tetrachloride (CCl4) exposure. Mice were given CCl4 once, and were euthanized 12 to 96 hours later. Relative to 6J mice, we found that 6N mice had increased liver injury but more rapid repair. This was due to the increased speed with which necrotic hepatocytes were removed in 6N mice and was directly related to increased recruitment of macrophages to the liver. In parallel, enhanced liver regeneration was observed in 6N relative to 6J mice. Hepatic stellate cell activation occurred earlier in 6N mice, but there was no difference in matrix metabolism between substrains. Taken together, these data demonstrate specific and significant differences in how the C57BL/6 substrains respond to acute CCl4, which has important implications for all mouse studies utilizing this model121018*^RefMgr field[33]: Not in FileB?9Megna, M. Napolitano, M. Costa, C. Balato, N. Patruno, C.2017 Waste exposure and skin diseases0Giornale Italiano di Dermatologia e Venereologia1online early: doi: 10.23736/S0392-0488.17.05505-5not published, 01 Mar 17,Adverse ADVERSE EFFECTS As chemical CHEMICALS CLINICAL CUTANEOUS DATA DERMAL DISEASE DUST ENDOTOXIN epidemiological EXPOSURE GASTROINTESTINAL hazardous HAZARDOUS WASTE HEALTH Health risk Health risks HUMAN Human health INORGANIC IS MEMBRANE ORGANIC POLLUTION RESPIRATORY REVIEW RISK SKIN SURVEY toxic 2/16/2017Waste is a composite mixture of different substances including endotoxins, organic dust and bio-aerosol stuffed with micro-organisms, as well as various toxic organic and inorganic chemicals, which may be intrinsically hazardous to human health. Therefore, health risks may derive from direct or indirect contact with garbage. Although few epidemiological and clinical surveys investigated on the adverse effects of garbage exposure on human health, particularly regarding respiratory, gastrointestinal, musculoskeletal and mucous membranes systems, only very limited data are available on the relationship between waste exposure and cutaneous diseases. However, the skin is the main external barrier of human body being deeply influenced by external hazardous factors. In this article we attempt to provide a state-of-the-art review on what is currently known about the relationship between waste exposure and skin diseases1210170 field[33]: Not in File ?Mehra, L. Hasija, Y. Mittal, G.2016aTherapeutic potential of alpha-ketoglutarate against acetaminophen-induced hepatotoxicity in rats296-299*Journal of Pharmacy and Bioallied Sciences84 ACETAMINOPHEN ACID ALANINE ALKALINE ALKALINE PHOSPHATASE AMINO ACID ANIMAL Animals As CAT CATALASE co-administration DIETARY DISEASE dose evidence GLUTATHIONE GSH HEPATOTOXICITY HISTOPATHOLOGY INFLAMMATION INJECTION INTRAPERITONEAL IS LEVELS LIVER MDA METABOLISM METABOLITE method methods NECROSIS NITROGEN over the counter OXIDATIVE STRESS P PARACETAMOL RAT rats Reduced glutathione Reduction SEVERITY STATUS STRESS STUDY SUPEROXIDE SUPEROXIDE DISMUTASE Synthesis THERAPEUTIC Toxicities TOXICITY TRANSPORT TREATMENT Vehicle10/2016OBJECTIVE: Alpha-ketoglutarate (alpha-KG) is a cellular intermediary metabolite of Krebs cycle, involved in energy metabolism, amino acid synthesis, and nitrogen transport. It is available over-the-counter and marketed as a nutritional supplement. There is a growing body of evidence to suggest that dietary alpha-KG has the potential to maintain cellular redox status and thus can protect various oxidative stress induced disease states. The aim of the present study was to investigate the hepatoprotective role of alpha-KG in acetaminophen (APAP) induced toxicity in rats. MATERIALS AND METHODS: Animals were divided into three groups of six animals each. Group I (Vehicle control): Normal Saline, Group II (APAP): A single intraperitoneal injection of 0.6 g/kg, Group III (APAP + alpha-KG): APAP as in Group II with alpha-KG treatment at a dose of 2 g/kg, orally for 5 days. Then the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) with oxidative stress markers including malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and histopathology were analyzed. RESULTS: The results indicate that APAP caused significant elevations in ALT, AST, ALP, and MDA levels, while GSH, SOD, and CAT were significantly depleted while co-administration of alpha-KG showed a significant (P < 0.05) reduction in the severity of these damages. Histologically, the liver showed inflammation and necrosis after APAP treatment, which were significantly restored with co-administration of alpha-KG. CONCLUSION: These results indicate the possible therapeutic potential of alpha-KG in protecting liver damage by APAP in rats121056- field[33]: Not in File B?>Meier, S.I. Koelzer, S.C. Schubert-Zsilavecz, M. Toennes, S.W.2017wAnalysis of drugs of abuse in cerumen - correlation of postmortem analysis results with those for blood, urine and hairDrug Testing and Analysis#online early: doi: 10.1002/dta.2177not published, 01 Mar 17ABUSE ALCOHOL ALCOHOL ABUSE amphetamine analysis ANALYTICAL As ASSESSMENT BLOOD CANNABINOID cannabinoids cannabinol CANNABIS case CHROMATOGRAPHY COCAINE DETECTION DIAZEPAM DRUG DRUG ABUSE Drug use drugs Drugs of abuse EVALUATION FORENSIC Forensic toxicology GA GAS GAS CHROMATOGRAPHY GC-MS HAIR IS LC-MS Liquid chromatography MASS SPECTROMETRY METABOLITE Metabolites METHADONE OPIATES POSTMORTEM RESEARCH SPECTROMETRY STUDY SUBSTANCE ABUSE SWEAT Testing tetrahydrocannabinol THC Time TOXICOLOGY URINE use 2/27/2017;The evaluation of drug and alcohol abuse is a major subject of forensic toxicology. Assessment of drug abstinence currently requires the analysis of urine or hair. In the present study cerumen, a mixture of sebum and sweat, was tested as an alternative. Postmortem samples (blood, urine, hair and cerumen from 38 corpses) were analyzed using liquid chromatography and gas chromatography, each coupled to mass spectrometry (LC-MS, GC-MS). The results were compared. In all cases of recent drug use (i.e. detection of opiates, amphetamine and derivatives, cocaine, methadone and diazepam or their metabolites in blood) the corresponding cerumen was positive. In 3 cases, where drugs could only be detected in urine, cerumen was also found to be positive. Even in cases where only hair was positive cerumen still contained analytes in some instances (52.5 %). However, cannabis use was only detected in 31.6 % of cerumen samples of the deceased cannabis users. Unexpectedly, not tetrahydrocannabinol (THC) was detected but its oxidized form, cannabinol. The present results suggest that cerumen is a promising alternative for drugs of abuse testing. The detection time window of cerumen is obviously in excess of that of urine but not as long as with hair. However, current problems with the detection of cannabinoids require further research120981" field[33]: Not in File~B?OMenaker, N. Halligan, K. Shur, N. Paige, J. Hickling, M. Nepo, A. Weintraub, L.2017NAcute liver failure during deferasirox chelation: a toxicity worth considering(Journal of Pediatric Hematology/Oncology/online early: doi: 10.1097/MPH.0000000000000786not published, 01 Mar 177ACUTE acute liver failure agent anemia Bilirubin case CASE REPORT Case-report CELL CHELATING AGENTS CHELATION CHRONIC DEFERASIROX FAILURE Ferritin HEPATIC HEPATIC FAILURE injuries Injury IS LIVER Liver failure MALE MONITORING PAEDIATRIC PATIENT PROTOCOL RENAL reversible Syndrome Toxicities TOXICITY transfusion 2/17/2017This case report details a unique case of acute, reversible liver failure in a 12-year-old male with sickle cell anemia on chronic transfusion protocol and deferasirox chelation. There is substantial literature documenting deferasirox-induced renal injury, including Fanconi syndrome, but less documentation of hepatic toxicity and few reports of hepatic failure. The case highlights the importance of close monitoring of ferritin, bilirubin, and transaminases for patients on deferasirox121054. field[33]: Not in File?Menecier, P. Rotheval, L.2017![Alcohol intoxication in old age]21-24Soins Gerontologie22123^ACUTE ADDICTION Age ALCOHOL CLINICAL CONFUSION DOE ELDERLY GERIATRIC INTOXICATION IS TREATMENT1/2017Acute alcohol intoxication occurs in elderly subjects. Drunkenness appears in banal clinical forms in geriatrics: falls, dizziness or confusion. Elderly people are more vulnerable to alcohol and need less alcohol to become intoxicated. Age does not exclude the possibility of receiving alcohol addiction treatment. Broaching the subject with an elderly person, the day after a drunken episode, is useful and recommended121183, field[22]: In French with English abstract RefMgr field[33]: Not in File?Meysman, T. Goossens, A.2016_Occupational allergic contact dermatitis caused by benzisothiazolinone in printing ink and soap51-53Contact Dermatitis761ACRYLATES agent allergic contact dermatitis allergies ALLERGY ANTIMICROBIAL ARABIC As baseline BENZISOTHIAZOLINONE biocide case CASE REPORT case reports Case-report COBALT CONTACT DERMATITIS COSMETIC Cosmetics DERMAL DERMATITIS ECZEMA EXPOSURE Fixed GLUE Guidelines GUM Hand HEALTH HI history HOUSEHOLD INDUSTRIAL INK IS Knowledge Laboratories LABORATORY Leather MALE NICKEL NO Occupation OCCUPATIONAL OIL PAINT PAPER PATCH patch testing PATIENT PET PRESERVATIVE REACTIONS REMISSION SKIN SOAP Sweden SYSTEMIC TEST Testing Time US use workers2016120824# field[33]: Not in File7B?(Middelberg, L.K. Chhabra, N. Mycyk, M.B.2017)Carbon monoxide Intoxication of childhoodPediatric Emergency Care/online early: doi: 10.1097/PEC.0000000000001055not published, 28 Feb 178carbon CARBON MONOXIDE childhood INTOXICATION PAEDIATRIC2/4/2017120915. field[33]: Not in File ?5Mielke, H.W. Gonzales, C.R. Powell, E.T. Mielke, P.W.2017Spatiotemporal exposome dynamics of soil lead and children's blood lead pre- and ten years post-Hurricane Katrina: Lead and other metals on public and private properties in the city of New Orleans, Louisiana, U.S.A208-218Environmental Research155Association BLOOD Blood lead childhood CHILDREN DATA DATABASE GASOLINE Housing IS LEAD Lead Poisoning METALS method methods PAEDIATRIC PAINT POISONING PREVENTION PUBLIC Redistribution RESIDENTIAL SOIL STUDY Toxicant Urban use 2/20/2017BACKGROUND: Anthropogenic re-distribution of lead (Pb) principally through its use in gasoline additives and lead-based paints have transformed the urban exposome. This unique study tracks urban-scale soil Pb (SPb) and blood Pb (BPb) responses of children living in public and private communities in New Orleans before and ten years after Hurricane Katrina (29 August 2005). OBJECTIVES: To compare and evaluate associations of pre- and ten years post-Katrina SPb and children's BPb on public and private residential census tracts in the core and outer areas of New Orleans, and to examine correlations between SPb and nine other soil metals. METHODS: The Louisiana Healthy Housing and Childhood Lead Poisoning Prevention Program BPb (microg/dL) data from pre- (2000-2005) and post-Katrina (2010-2015) for /=5microg/dL on public and private core areas pre-Katrina was 63.2% and 67.5%, and declined post-Katrina to 7.6% and 20.2%, respectively. BPb decreases also occurred in outer areas. Soil Pb is strongly correlated with other metals. CONCLUSIONS: Post-Katrina re-building of public housing plus landscaping amends the exposome and reduces children's BPb. Most importantly, Hurricane Katrina revealed that decreasing the toxicants in the soil exposome is an effective intervention for decreasing children's BPb120986. field[33]: Not in File ?Minigalieva, I.A. Katsnelson, B.A. Panov, V.G. Privalova, L.I. Varaksin, A.N. Gurvich, V.B. Sutunkova, M.P. Shur, V.Y. Shishkina, E.V. Valamina, I.E. Zubarev, I.V. Makeyev, O.H. Meshtcheryakova, E.Y. Klinova, S.V.2017In vivo toxicity of copper oxide, lead oxide and zinc oxide nanoparticles acting in different combinations and its attenuation with a complex of innocuous bio-protectors72-93 Toxicology380%AIRWAY Airways As BLOOD BRONCHOALVEOLAR LAVAGE case Combined toxicity COPPER dose EXCRETION EXPOSURE IN VIVO INJECTION INTERACTION INTOXICATION IS LASER LAVAGE LEAD LEVELS METALS NANOPARTICLES RAT rats SALT SPECIES STUDY SUBCHRONIC Time toxic Toxicities TOXICITY URINE US WATER ZINC ZINC OXIDE 2/15/2017Stable suspensions of metal oxide nanoparticles (Me-NPs) obtained by laser ablation of 99.99% pure copper, zinc or lead under a layer of deionized water were used separately, in three binary combinations and a triple combination in two independent experiments on rats. In one of the experiments the rats were instilled with Me-NPs intratracheally (i.t.) (for performing a broncho-alveolar lavage in 24h to estimate the cytological and biochemical indices of the response of the lower airways), while in the other, Me-NPs were repeatedly injected intraperitoneally (i.p.) 18 times during 6 weeks (for estimating the accumulation of corresponding metals in the blood and their excretion with urine and feces and for assessing subchronic intoxication by a large number of functional and morphological indices). Mathematical description of the results from both experiments with the help of the Response Surface Methodology has shown that, as well as in the case of any other binary toxic combinations previously investigated by us, the response of the organism to a simultaneous exposure to any two of the Me-NPs under study is characterized by complex interactions between all possible types of combined toxicity (additivity, subadditivity or superadditivity of unidirectional action and different variants of opposite effects) depending on which effect it is estimated for as well as on the levels of the effect and dose. With any third Me-NP species acting in the background, the type of combined toxicity displayed by the other two may change significantly (as in the earlier described case of a triple combination of soluble metal salts). It is shown that various harmful effects produced by CuO-NP+ZnO-NP+PbO-NP combination may be substantially attenuated by giving rats per os a complex of innocuous bioactive substances theoretically expected to provide a protective integral and/or metal-specific effect during one month before i.t. instillation or during the entire period of i.p. injections121128+ field[33]: Not in File`? <Mishra, A.K. Chandiraseharan, V.K. Jose, N. Sudarsanam, T.D.2016?Chlorantraniliprole: an unusual insecticide poisoning in humans742-744(Indian Journal of Critical Care Medicine2012case CHLORANTRANILIPROLE CONDUCTION CONDUCTION DEFECT FEMALE HUMAN human toxicology Humans INSECTICIDE Insecticides IS Knowledge Observation POISONING RECEPTORS TOXICOLOGY12/2016EA 26-year-old female presented with deliberate self-harm using chlorantraniliprole, an unknown substance in human toxicology. She developed symptomatic Mobitz Type I atrioventricular block during observation, for which a temporary pacemaker was inserted. She reverted to sinus rhythm after 48 h and was discharged. Although claimed to be nontoxic to humans, chlorantraniliprole, an insecticide, could cause conduction defects by activating ryanodine receptors. To the best of our knowledge, this is the first case of chlorantraniliprole poisoning reported in the medical literature120735* field[22]: PMC5225778 RefMgr field[33]: year=2016 volume=20 issue=12 spage=742 epage=744 aulast=Mishra Not in File ? 9Misra, S.C. Gabriel, L. Nacoulma, E. Dine, G. Guarino, V.2017FHow to diagnose early 5-azacytidine-induced pneumonitis: a case report4Drug Safety - Case Reports41]ABUSE ACID ANTIBIOTIC Antibiotics ANTINEOPLASTIC DRUGS Body Weight Broad spectrum BRONCHOALVEOLAR LAVAGE case CASE REPORT Case-report CEFTAZIDIME CELL CIPROFLOXACIN computed tomography Cough Development DIAGNOSIS DOSAGE dose DRUG drug-induced drugs Emergencies emergency FEMALE Fever high resolution computed tomography HOSPITAL HYPERSENSITIVITY INFECTION IS IV LAVAGE MYCOBACTERIUM TUBERCULOSIS NEUTROPENIA opacity PATIENT PNEUMONITIS Polymerase Chain Reaction PROTOCOL PULMONARY PULMONARY TOXICITY SYMPTOMS Syndrome t TEMPERATURE THERAPY Time TOMOGRAPHY Toxicities TOXICITY TREATMENT TUBERCULOSIS WEIGHT12/2017eInterstitial pneumonitis is a classical complication of many drugs. Pulmonary toxicity due to 5-azacytidine, a deoxyribonucleic acid methyltransferase inhibitor and cytotoxic drug, has rarely been reported. We report a 67-year-old female myelodysplastic syndrome patient treated with 5-azacytidine at the conventional dosage of 75 mg/m2 for 7 days. One week after starting she developed moderate fever along with dry cough and subsequently her temperature rose to 39.5 degrees C. She was placed under broad-spectrum antibiotics based on the protocol for febrile neutropenia, including ciprofloxacin 750 mg twice daily, ceftazidime 1 g three times daily (tid), and sulfamethoxazole/trimethoprim 400 mg/80 mg tid. High-resolution computed tomography of the chest disclosed diffuse bilateral opacities with ground-glass shadowing and pleural effusion bilaterally. Mediastinal and hilar lymph nodes were moderately enlarged. polymerase chain reaction for Mycobacterium tuberculosis, Pneumocystis jiroveci, and cytomegalovirus were negative. Cultures including viral and fungal were all negative. A diagnosis of drug-induced pneumonitis was considered and, given the negative bronchoalveolar lavage in terms of an infection, corticosteroid therapy was given at a dose of 1 mg/kg body weight. Within 4 weeks, the patient became afebrile and was discharged from hospital. Development of symptoms with respect to drug administration, unexplained fever, negative workup for an infection, and marked response to corticosteroid therapy were found in our case. An explanation could be a delayed type of hypersensitivity (type IV) with activation of CD8 T cell which could possibly explain most of the symptoms. We have developed a decision algorithm in order to anticipate timely diagnosis of 5-azacitidine-induced pneumonitis, and with the aim to limit antibiotics abuse and to set up emergency treatment120980+ field[33]: Not in File/? "Mohebali, D. Matos, J. Chang, J.D.2017IGemcitabine induced cardiomyopathy: a case of multiple hit cardiotoxicity71-74ESC Heart Failure41agent CANCER CARDIAC CARDIOMYOPATHY CARDIOTOXICITY case dose GEMCITABINE IS LYMPHOMA MECHANISM Side effect side effects side-effects use WHO2/2017Gemcitabine is a commonly used antineoplastic agent used to treat a variety of cancers with rarely reported cardiac side effects. We describe a case of a 67-year-old woman with follicular lymphoma who experienced a rarely reported side effect of gemcitabine: cardiomyopathy. This case highlights a multiple hit mechanism of myocyte damage that may occur following the use of multiple cardio-toxic agents despite their administration in doses not associated with cardiotoxicity120999' field[33]: Not in File -B? dMonteiro, K. Dumenco, L. Collins, S. Bratberg, J. MacDonnell, C. Jacobson, A. Dollase, R. George, P.2017}An interprofessional education workshop to develop health professional student opioid misuse knowledge, attitudes, and skills2Journal of the American Pharmaceutical Association-online early: doi: 10.1016/j.japh.2016.12.069not published, 21 Feb 17EAs ASSESSMENT baseline case DATA EDUCATION EVALUATION FOLLOW UP Follow-up HEALTH HIGH LEVELS Knowledge LEVELS medical student Medicine MISUSE NALOXONE NURSING OPIOID Opioid overdose opioid use disorder Opioids OVERDOSE P PATIENT quality satisfaction SCALE School SOCIAL Substance use substance use disorder SURVEY THERAPY use 1/31/2017AOBJECTIVE: To implement and evaluate an interprofessional workshop focused on increasing student knowledge, skills, and attitudes toward opioid misuse. SETTING: The Warren Alpert Medical School of Brown University in Providence, Rhode Island, April 2016. PRACTICE DESCRIPTION: Health professional students from medicine, nursing, pharmacy, social work, and physical therapy participated in an interprofessional education workshop focused on opioid use disorder. PRACTICE INNOVATION: This workshop included 4 main components: a patient panel, a simulated standardized patient encounter, a paper-based case session focused on a homeless individual misusing opioids, and naloxone training. EVALUATION: Direct assessment included a pretest and a posttest adapted from the Opioid Overdose Knowledge Scale administered to medical students measuring knowledge of opioid overdose at baseline and at 12 weeks after the workshop. Indirect assessment included a satisfaction survey administered to medical, nursing, pharmacy, and social work students. RESULTS: Medical students scored a mean of 40.84 out of 54 (SD = 5.36) points at baseline (n = 120) and a mean of 47.94 out of 54 (SD = 3.20) points at 12-week follow-up (n = 72), demonstrating a significant increase in knowledge from pretest to posttest (P <0.001). Student satisfaction data from medicine, nursing, pharmacy, social work, and physical therapy (n = 272) revealed a high degree of satisfaction regarding the overall quality of the training (4.47/5; SD = 0.75), quality of instruction (4.53/5; SD = 0.73), quality of training materials (4.46/5; SD = 0.77), the training experience (4.52/5; SD = 0.75), and the organization of the training (4.50/5; SD = 0.73). CONCLUSION: Our results demonstrate that an interprofessional education workshop focused exclusively on opioid misuse was well received with high levels of satisfaction among health professional students. Workshops such as these can be used in health professions curricula to simulate the complex issues surrounding substance use disorder and to highlight the importance of interprofessional teams120790, field[33]: Not in File EB? Mooij, M.G. van Duijn, E. Knibbe, C.A. Allegaert, K. Windhorst, A.D. van Rosmalen, J. Hendrikse, N.H. Tibboel, D. Vaes, W.H. de Wildt, S.N.2017dSuccessful use of [14C]paracetamol microdosing to elucidate developmental changes in drug metabolismClinical Pharmacokinetics,online early: doi: 10.1007/s40262-017-0508-6not published, 16 Feb 17sAge As burden CHILDREN CLEARANCE DEVELOPMENTAL DISPOSITION DISTRIBUTION DRUG INFANT Infants INTENSIVE CARE intensive care unit INTRAVENOUS IS KINETICS MASS SPECTROMETRY METABOLISM METABOLITE Metabolites method methods ORAL PAEDIATRIC PARACETAMOL pharmacokinetic PLASMA recovery RISK SPECTROMETRY STUDY THERAPEUTIC Time UNIT urinary URINE use Volume Volume of distribution2/2/2017BACKGROUND: We previously showed the practical and ethical feasibility of using [14C]-microdosing for pharmacokinetic studies in children. We now aimed to show that this approach can be used to elucidate developmental changes in drug metabolism, more specifically, glucuronidation and sulfation, using [14C]paracetamol (AAP). METHODS: Infants admitted to the intensive care unit received a single oral [14C]AAP microdose while receiving intravenous therapeutic AAP every 6 h. [14C]AAP pharmacokinetic parameters were estimated. [14C]AAP and metabolites were measured with accelerator mass spectrometry. The plasma area under the concentration-time curve from time zero to infinity and urinary recovery ratios were related to age as surrogate markers of metabolism. RESULTS: Fifty children [median age 6 months (range 3 days-6.9 years)] received a microdose (3.3 [2.0-3.5] ng/kg; 64 [41-71] Bq/kg). Plasma [14C]AAP apparent total clearance was 0.4 (0.1-2.6) L/h/kg, apparent volume of distribution was 1.7 (0.9-8.2) L/kg, and the half-life was 2.8 (1-7) h. With increasing age, plasma and urinary AAP-glu/AAP and AAP-glu/AAP-sul ratios significantly increased by four fold, while the AAP-sul/AAP ratio significantly decreased. CONCLUSION: Using [14C]labeled microdosing, the effect of age on orally administered AAP metabolism was successfully elucidated in both plasma and urine. With minimal burden and risk, microdosing is attractive to study developmental changes in drug disposition in children120728+ field[33]: Not in FileUB?6More, S.S. Nugent, J. Vartak, A.P. Nye, S.M. Vince, R.2017\Hepatoprotective effect of psi-GSH in a murine model of acetaminophen-induced liver toxicityChemical Research in Toxicology1online early: doi: 10.1021/acs.chemrestox.6b00291not published, 28 Feb 17&ACETAMINOPHEN agent analysis As Characterization chemical DRUG EFFICACY Emergencies emergency EVALUATION GLUTATHIONE GSH HEPATOTOXICITY IS LIVER LIVER FUNCTION Medicine METABOLITE MODEL N-ACETYLCYSTEINE NAC NAPQI ORAL OVERDOSE PARACETAMOL SURVIVAL TEST Time toxic Toxicities TOXICITY TOXICOLOGY2/6/2017Psi-glutathione (psi-GSH) is an orally bioavailable and metabolism-resistant glutathione analogue that has been shown previously to substitute glutathione in most of its biochemical roles. Described here in its entirety is the preclinical evaluation of psi-GSH as a rescue agent for acetaminophen (APAP) overdose: an event where time is of essence. Employing a murine model, four scenarios commonly encountered in emergency medicine are reconstructed. psi-GSH is juxtaposed against N-acetylcysteine (NAC), the sole clinically available drug, in each of the scenarios. While both agents appear to be equally efficacious when timely administered, psi-GSH partly retains its efficacy even in the face of substantial delay in administration. Thus implied is the ability of psi-GSH to intercept secondary toxicology following APAP insult. Oral availability and complete lack of toxicity as evaluated by liver function tests and survival analysis underscored psi-GSH as a safer and more efficacious alternative to NAC. Finally, the pharmacodynamic mimicry of GSH by psi-GSH is illustrated through the isolation and chemical characterization of an entity that can arise only through direct encounter of psi-GSH with NAPQI, the primary toxic metabolite of APAP1208620 field[33]: Not in FileB?=Morgan, J.C. Byron, M.J. Baig, S.A. Stepanov, I. Brewer, N.T.2017LHow people think about the chemicals in cigarette smoke: a systematic review J Behav Med,online early: doi: 10.1007/s10865-017-9823-5not published, 01 Mar 17Awareness Behavior chemical CHEMICALS CIGARETTE Cigarette smoke Cigarettes citations INFORMATION IS Knowledge MET PUBLIC RESEARCH REVIEW RISK Risk perception SMOKE systematic review TOBACCO TOXICOLOGY 2/21/2017-Laws and treaties compel countries to inform the public about harmful chemicals (constituents) in cigarette smoke. To encourage relevant research by behavioral scientists, we provide a primer on cigarette smoke toxicology and summarize research on how the public thinks about cigarette smoke chemicals. We systematically searched PubMed in July 2016 and reviewed citations from included articles. Four central findings emerged across 46 articles that met inclusion criteria. First, people were familiar with very few chemicals in cigarette smoke. Second, people knew little about cigarette additives, assumed harmful chemicals are added during manufacturing, and perceived cigarettes without additives to be less harmful. Third, people wanted more information about constituents. Finally, well-presented chemical information increased knowledge and awareness and may change behavior. This research area is in urgent need of behavioral science. Future research should investigate whether educating the public about these chemicals increases risk perceptions and quitting121038+ field[33]: Not in File ?)Morgan, M. Jones, P. Sobus, J. Barr, D.B.2016NPredictors of urinary 3-phenoxybenzoic acid levels in 50 North Carolina adults 1172-1185AInternational Journal of Environmental Research and Public Health1311ACID ADULT analysis Association author Biomarker BIOMARKERS biomonitoring COFFEE CONCENTRATIONS Consumption CREATININE DATA Diaries Diary DIETARY Environment EXPOSURE FOOD HUMAN Human exposure impact INSECTICIDE Insecticides IS LEVELS lifestyle Liquid chromatography tandem mass spectrometry Liquid chromatography-tandem mass spectrometry MASS SPECTROMETRY Measurement METABOLITE P pesticide py PYRETHROID Pyrethroids SPECTROMETRY STUDY Time urinary URINE use2016Limited data are available on the non-chemical stressors that impact adult exposures to pyrethroid insecticides based on urinary biomonitoring. The urinary metabolite, 3-phenoxybenzoic acid (3-PBA), is commonly used to assess human exposure to a number of pyrethroids. In a further analysis of published study data, we quantified urinary 3-PBA levels of 50 adults over a single, 24-h sampling period and examined the associations between the biomarker measurements and selected non-chemical stressors (demographic, lifestyle, and dietary factors). A convenience sample of 50 adults was recruited in North Carolina in 2009-2011. Participants collected individual urine voids (up to 11) and filled out activity, food, and pesticide use diaries over a 24-h sampling period. Urine voids (n = 326) were analyzed for 3-PBA concentrations using high-performance liquid chromatography-tandem mass spectrometry. 3-PBA was detected in 98% of the 24-h composited urine samples. The geometric mean urinary 3-PBA level was 1.68 ng/mL in adults. Time spent outside (p = 0.0006) was a highly significant predictor of natural log-transformed (ln) urinary 3-PBA levels, while consumption of coffee (p = 0.007) and breads (p = 0.019) and ln creatinine levels (p = 0.037) were significant predictors of urinary 3-PBA levels. In conclusion, we identified specific factors that substantially increased adult exposures to pyrethroids in their everyday environments. Copyright © 2016 by the authors; licensee MDPI, Basel, Switzerland120826( field[33]: Not in File?Mossanen, J.C. Tacke, F.20150Acetaminophen-induced acute liver injury in mice30-36Laboratory animals49 1 SupplementSACETAMINOPHEN ACUTE acute liver failure ANIMAL As Environment EXPERIMENTAL FAILURE genetic HEPATIC HEPATOTOXICITY HUMAN Humans INDUCTION injuries Injury IS LIVER Liver failure liver injury MICE MODEL mouse OVERDOSE PARACETAMOL PATHOGENESIS PATIENT POISONING PROGNOSIS PROTOCOL RESEARCH Route Sex THERAPEUTIC Toxicities TOXICITY Variability2015The induction of acute hepatic damage by acetaminophen (N-acetyl-p-aminophenol [APAP]), also termed paracetamol, is one of the most commonly used experimental models of acute liver injury in mice. The specific values of this model are the highly reproducible, dose-dependent hepatotoxicity of APAP and its outstanding translational importance, because acetaminophen overdose is one of the most frequent reasons for acute liver failure (ALF) in humans. However, preparation of concentrated APAP working solutions, application routes, fasting period and variability due to sex, genetic background or barrier environment represent important considerations to be taken into account before implementing this model. This standard operating procedure (SOP) provides a detailed protocol for APAP preparation and application in mice, aimed at facilitating comparability between research groups as well as minimizing animal numbers and distress. The mouse model of acetaminophen poisoning therefore helps to unravel the pathogenesis of APAP-induced toxicity or subsequent immune responses in order to explore new therapeutic interventions for improving the prognosis of ALF in patients. Copyright © The Author(s) 2015 Reprints and permissions:* field[33]: Not in File?CMostafazadeh, B. Shadnia, S. Tavakkoli, M.A. Khoddami Vishteh, H.R.2017AEvaluation of blood lead level in methamphetamine users in Tehran2Subst Abuse Treat Prev Policy121$Age AMFETAMINE BLOOD Blood lead case DOSAGE DRUG EVALUATION Heavy metal Heavy metal poisoning history INHALATION LEAD Lead Poisoning MALE METHAMPHETAMINE method methods NO OPIATES OPIOID Opioids ORAL PATIENT POISONING REVIEW Route route of administration Sex STUDY SYMPTOMS TEST URINE use WHO 2/22/2017BACKGROUND: Given the increasing number of lead poisoning in opioids users and since no study has been conducted so far to review lead poisoning in methamphetamine (crystal) users, this study aimed to investigate blood lead level in methamphetamine addicts. METHODS: This study was conducted on 20 patients with methamphetamine poisoning and their blood lead level was measured. The subjects were selected from among patients with a history of continuous use of methamphetamine, without a history of using opiates in the past 6 months confirmed by a negative urine tests, and without a history of heavy metal poisoning. RESULTS: Of all, 18 patients were male and the mean age was 32 +/- 10 years; 17 patients were abusing the drug via inhalation and three persons via oral administration. The mean blood lead level was 2.3 +/- 1.1 mug/dL and poisoning was not observed in any of the cases. Blood lead level was not associated with age, sex, dosage, and route of administration. CONCLUSION: Although blood lead level was not at poisoning level in people who only used methamphetamine in Iran, due to the simultaneous use of other substances and because of non-specific symptoms, lead poisoning must be suspected in all cases of substances poisoning121117+ field[33]: Not in FileB?#Mudge, E.M. Murch, S.J. Brown, P.N.2017+Leaner and greener analysis of cannabinoids&Analytical and Bioanalytical Chemistry,online early: doi: 10.1007/s00216-017-0256-3not published, 01 Mar 17?analysis ANALYTICAL CANNABINOID cannabinoids CANNABIS CHEMISTRY 2/23/2017\There is an explosion in the number of labs analyzing cannabinoids in marijuana (Cannabis sativa L., Cannabaceae) but existing methods are inefficient, require expert analysts, and use large volumes of potentially environmentally damaging solvents. The objective of this work was to develop and validate an accurate method for analyzing cannabinoids in cannabis raw materials and finished products that is more efficient and uses fewer toxic solvents. An HPLC-DAD method was developed for eight cannabinoids in cannabis flowers and oils using a statistically guided optimization plan based on the principles of green chemistry. A single-laboratory validation determined the linearity, selectivity, accuracy, repeatability, intermediate precision, limit of detection, and limit of quantitation of the method. Amounts of individual cannabinoids above the limit of quantitation in the flowers ranged from 0.02 to 14.9% w/w, with repeatability ranging from 0.78 to 10.08% relative standard deviation. The intermediate precision determined using HorRat ratios ranged from 0.3 to 2.0. The LOQs for individual cannabinoids in flowers ranged from 0.02 to 0.17% w/w. This is a significant improvement over previous methods and is suitable for a wide range of applications including regulatory compliance, clinical studies, direct patient medical services, and commercial suppliers.120941, field[33]: Not in File B?Murphy, S.M. Polsky, D. Lee, J.D. Friedmann, P.D. Kinlock, T.W. Nunes, E.V. Bonnie, R.J. Gordon, M. Chen, D.T. Boney, T.Y. O'Brien, C.P.2017Cost-effectiveness of extended release naltrexone to prevent relapse among criminal-justice-involved persons with a history of opioid use disorder Addiction$online early: doi: 10.1111/add.13807not published, 01 Mar 17ADULT As CLINICAL COST DEATH Deaths DOE effectiveness EVALUATION FOLLOW UP Follow-up history INJECTION IS Measurement NALTREXONE OPIOID opioid use disorder Opioids quality Quality of life Randomized trial Release STUDY TREATMENT TRIAL use 2/26/2017>BACKGROUND/AIMS: Criminal-justice-involved persons are highly susceptible to opioid relapse and overdose-related deaths. In a recent randomized trial, we demonstrated the effectiveness of extended release naltrexone (XR-NTX; Vivitrol(R)) in preventing opioid relapse among criminal-justice-involved U.S. adults with a history of opioid use disorder. The cost of XR-NTX may be a significant barrier to adoption. Thus, it is important to account for improved quality of life, and downstream cost-offsets. Our aims were to (1) estimate the incremental cost per quality-adjusted life-year (QALY) gained for XR-NTX versus treatment as usual (TAU), and evaluate it relative to generally-accepted value thresholds; and (2) estimate the incremental cost per additional year of opioid abstinence. DESIGN: Economic evaluation of the aforementioned trial from the taxpayer perspective. Participants were randomized to 25 weeks of XR-NTX injections or TAU; follow-up occurred at 52 and 78 weeks. SETTING: Five study sites in the U.S. Northeast corridor. PARTICIPANTS: 308 participants were randomized to XR-NTX (n = 153) or TAU (n = 155). MEASUREMENTS: Incremental costs relative to incremental economic and clinical effectiveness measures, QALYs and abstinent-years, respectively. FINDINGS: The 25-week cost-per-QALY and -abstinent-year figures were $162,150 and $46,329, respectively. The 78-week figures were $76,400/QALY and $16,371/abstinent-year. At 25 weeks, we can be 10% certain that XR-NTX is cost-effective at a value threshold of $100,000/QALY, and 62% certain at $200,000/QALY. At 78 weeks, the cost-effectiveness probabilities are 59% at $100,000/QALY and 76% at $200,000/QALY. We can be 95% confident that the intervention would be considered a "good-value" at $90,000/abstinent-year at 25 weeks, and $500/abstinent-year at 78 weeks. CONCLUSIONS: While extended release naltrexone appears to be effective in increasing both quality-adjusted life-years (QALYs) and abstinence, it does not appear to be cost-effective using generally-accepted value thresholds for QALYs, due to the high price of the injection120931# field[33]: Not in File,B?=Mygatt, J. Amani, M. Ng, P. Benson, B. Pamplin, J. Cancio, L.20174Hydrocarbon enema: an unusual cause of chemical burnJ Burn Care Res/online early: doi: 10.1097/BCR.0000000000000509not published, 01 Mar 17As Burn BURNS case case studies Case Study chemical chemical burn CHEMICALS DECONTAMINATION DERMAL Dermal exposure Diarrhea ENEMA EXPOSURE FEMALE HYDROCARBON INGESTION IS Knowledge MANAGEMENT PATIENT PERINEUM POISONING RECTAL REVIEW STUDY SUICIDE TREATMENT WHO 2/13/2017Hydrocarbons are a wide-ranging group of flammable chemicals and are often used in suicide attempts either by ingestion or as accelerant in self-immolation. In this case study, we present a 37-year-old female who suffered 6% TBSA partial-thickness burns to her perineum and buttocks, which she claims resulted from diarrhea after ingesting a bottle of lighter fluid. The patient underwent decontamination and medical treatment for her burns and during her inpatient stay, it became apparent that the burns were more likely sustained from an intentional rectal administration of lighter fluid. To our knowledge, this is one of the first reported cases of hydrocarbon enema. We review hydrocarbon poisoning, including both ingestion and dermal exposure, and discuss medical management121042. field[33]: Not in File _?J1Najjari, F. Ramazannejad, P. Ahmadi, A. Amini, Z.2016Epidemiological study of poisoning in patients referring educational and clinical center of Ayatollah Kashani Hospital, Shahrekord (West of Iran) throughout 2008-2014121-127AInternational Journal of Medical Toxicology and Forensic Medicine63kAge analysis Association Awareness BASE CLINICAL DATA DEATH Deaths DIAGNOSIS duration epidemiologic epidemiological EPIDEMIOLOGY FEMALE FORENSIC Forensic Medicine HOSPITAL hospitalization Incidence INFORMATION INJECTION IS MALE Medicine method methods MORTALITY ORAL P PATIENT POISONING poisonings RESPIRATORY SOFTWARE Source STATUS STUDY TOXICOLOGY TREATMENT use2016Background: Appropriate and early diagnosis and treatment of poisoning could be vital. Awareness of general pattern of poisoning in any geographical regions could be helpful in this regard. According to the lack of information and not being specified the epidemiologic forms of poisoning in Chaharmahal and Bakhtiari province (west of Iran), this study was carried out to determine the epidemiologic status of poisoning. Methods: In this routine data base study, available data were used in medical records of 394 patients with poisoning diagnosis throughout 2008-2014 at Ayatollah Kashani Hospital (only recipient hospital of poisoning in Chaharmahal and Bakhtiari province), which affiliated with Shahrekord University of Medical Sciences. Association between the studies was variable and also reasons for poisoning was investigated by chi-square, analysis of variance, independent t-test, Pearson's correlation in stata software. Results: Of 395 patients with poisoning, 207 (52.5%) were female and the rest were male. For the years under study, the highest poisoning ratio (20.26%) was seen in 2010 and the lowest (3%) in 2014. Mean age of all, male and female patients was 27.6, 29.8, and 25.6 years, respectively, with a significant difference between male and female patients (P < 0.05). The mean and standard deviation of duration of hospitalization in respiratory patients was 3.2+/-4.2, injection 3+/-3.8, oral 2.5+/-3, others 2+/-1.2, and bite was 2 days (P > 0.05). The highest poisoning ratio (62%) was obtained for oral poisonings and the lowest (0.5%) was due to beating. For marital status, the highest poisoning ratio was obtained in the single individuals and the lowest in the divorced (P < 0.05). Of 395 patients, 358 (90.6%) survived and the rest died. The highest mortality (17 deaths) was due to oral poisoning. Conclusion: Poisoning occurs often in young people and has a high load in this group. Trend of poisoning in this province is steadily diminishing. Epidemiological, regional data helps to use the sources appropriately to prevent and control poisoning. Further, analysis of the effective factors could contribute to decreasing poisoning incidence by planners and policymakers. Copyright © 2016 Forensic Medicine and Toxicology Department. All rights reserved120828E Not in File9?KNamal Rathnayaka, R.M.M.K. Kularatne, S.A.M. Nishanthi Ranathunga, P.E.A.N.2017zCoagulopathy and extensive local swelling following Green pit viper (Trimeresurus trigonocephalus) envenoming in Sri Lanka95-99Toxicon129bcase COAGULOPATHY envenoming FRESH FROZEN PLASMA IS PLASMA snake bite TREATMENT TRIMERESURUS VIPER 2/16/2017QTrimeresurus trigonocephalus (Sri Lankan Green pit viper) is a moderately venomous arboreal snake endemic to Sri Lanka. Even though, its bites are not uncommon, published reports of such cases are limited to three in literature. We report three cases of coagulopathy following Green pit viper bites and treatment with fresh frozen plasma121133/ field[33]: Not in FileO?Nasa, P. Juneja, D.2016DAcute pesticide ingestion managed with yohimbine as a rescue therapy739-741(Indian Journal of Critical Care Medicine2012VACCIDENTAL ACUTE AGRICULTURAL AMITRAZ ANIMAL ANTAGONIST ANTIDOTE As BRADYCARDIA case central nervous system child Convulsion CONVULSIONS DEPRESSION HUMAN Humans INGESTION INTOXICATION IS MANAGEMENT Mechanical ventilation Medicine NO pesticide POISONING RESPIRATORY RESPIRATORY DEPRESSION THERAPY TREATMENT VENTILATION Veterinary WHO YOHIMBINE12/2016Amitraz is used as a pesticide in agricultural and veterinary medicine. It is primarily a central alpha2 adrenergic agonist and known to cause central nervous system depression, convulsions, respiratory depression, and bradycardia on severe intoxication. We report a case of a 3-year-old child who presented with accidental ingestion of amitraz solution with signs of severe poisoning. There is no specific antidote of amitraz poisoning in humans, however, animal experiments with alpha2 adrenergic antagonists such as yohimbine and atimepazole have been successful. The child was managed besides intensive management with enteral yohimbine, and he regained consciousness in 18 h and was successfully weaned off mechanical ventilation120769* field[33]: year=2016 volume=20 issue=12 spage=739 epage=741 aulast=Nasa Not in File B?3Nault, R. Fader, K.A. Lydic, T.A. Zacharewski, T.R.2017Lipidomic evaluation of aryl hydrocarbon receptor-mediated hepatic steatosis in male and female mice by 2,3,7,8-tetrachlorodibenzo-p-dioxinChemical Research in Toxicology1online early: doi: 10.1021/acs.chemrestox.6b00430not published, 01 Mar 17 ACID ANIMAL Animals Aryl hydrocarbon receptor As CHOLESTEROL Confirmation DATA DIETARY DIOXIN dioxins ENVIRONMENTAL EVALUATION Fatty acids FEMALE FIBROSIS HEPATIC HYDROCARBON IS LIPID LIVER MALE METABOLISM MICE OLEATE PACKAGING Qualitative SPECIES TCDD TRIGLYCERIDE 2/27/2017The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces hepatic steatosis mediated by the aryl hydrocarbon receptor. To further characterize TCDD-elicited hepatic lipid accumulation, mice were gavaged with TCDD every 4 days for 28 days. Liver samples were examined using untargeted lipidomics with structural confirmation of lipid species by targeted high-resolution MS/MS and data were integrated with complementary RNA-Seq analyses. Approximately 936 unique spectral features were detected, of which 379 were confirmed as unique lipid species. Both male and female samples exhibited similar qualitative changes (lipid species), but differed in quantitative changes. A shift to higher mass lipid species was observed, indicative of increased free fatty acid (FFA) packaging. For example, of the 13 lipid classes examined, triglycerides increased from 46-48% of total lipids to 68-83% in TCDD treated animals. Hepatic cholesterol esters increased 11.3-fold in male mice with moieties consisting largely of dietary fatty acids (FAs) (i.e., linolenate, palmitate, and oleate). Phosphatidylserines, phosphatidylethanolamines, phosphatidic acids, and cardiolipins decreased 4.1-, 5.0-, 5.4- and 7.4-fold, respectively, while ceramides increased 6.6-fold. Accordingly, differential expression of lipid metabolism genes suggest increased hepatic uptake and packaging of lipids, while VLDL secretion is repressed. These changes are consistent with the progression of TCDD-elicited steatosis to steatohepatitis with fibrosis1209611 field[33]: Not in File q? Navarro, V.2016FLiver injury due to herbals, botanicals, and other dietary supplementsOA46 Planta Medica825agent ANTIMICROBIAL antimicrobials As Awareness case CASE REPORT case reports Case-report chemical CLINICAL DIETARY Dietary supplement Dietary supplements DRUG drug induced liver injury drug-induced drugs Hand HEALTH HEPATOTOXICITY HERBAL MEDICINE Herbals Ingredient injuries Injury IS JAUNDICE LIVER liver injury Liver Transplantation MECHANISM Medicine medicines MUSCLE PRURITUS use WEIGHT Weight Loss2016/There is an increasing awareness of liver injury resulting from herbals, botanicals, and other dietary supplements. The literature is rife with case reports of hepatotoxicity attributed to various single or multi-ingredient products. The U.S. Drug Induced Liver Injury Network (DILIN) was funded by the National Institutes of Health starting in 2003 to better understand the causes of liver injury from drugs and dietary supplements. The DILIN's early findings indicated that dietary supplements are the second most common types of agents to cause liver injury, after antimicrobials. Products used for the purposes of bodybuilding and muscle enhancement are the most common types of supplements implicated in liver injury. The injury resulting from those products is characteristic, with prolonged jaundice and pruritus being typical. On the other hand, injury resulting from non-bodybuilding products, such as those used for weight loss among other reasons, tends to be of a different pattern and more commonly associated with the need for liver transplantation than even injury resulting from prescription medications. Clinical investigators face several challenges in achieving a better understanding of liver injury due to herbals, botanicals, and other dietary supplements. Among them, the most vexing is the chemical complexity of supplements. This complexity prevents a firm attribution of liver injury to the precise ingredient, or combination of ingredients. An additional problem includes the lack of a standard nomenclature for marketed products which, in turn, confounds clinicians' ability to group products of similar composition or use. A standard nomenclature would allow clinicians to group products and recognize common patterns of injury. This, in turn, could give insight into the mechanism and precise causes of injury120804( field[33]: Not in File tB?Nelson, J.C. Spyker, D.A.2017Morbidity and mortality associated with medications used in the treatment of depression: an analysis of cases reported to U.S. Poison Control Centers, 2000-2014American Journal of Psychiatry1online early: doi: 10.1176/appi.ajp.2016.16050523not published, 16 Feb 17ACID agent analysis ANTICONVULSANT anticonvulsants ANTIDEPRESSANTS Antipsychotic antipsychotics author bupropion CARBAMAZEPINE case CITALOPRAM CLINICAL DATA DEPRESSION DRUG drugs EPIDEMIOLOGY EXPOSURE FATAL Fatal Outcome hazardous LITHIUM method MONOAMINE OXIDASE MONOAMINE OXIDASE INHIBITOR MORBIDITY MORTALITY OLANZAPINE outcome OVERDOSE PATIENT Poison poison centers Poison Control Centers QUETIAPINE RISK SUICIDE TREATMENT UNITED STATES VALPROIC ACID VENLAFAXINE ZIPRASIDONE 1/31/2017OBJECTIVE: The authors sought to determine the relative morbidity and mortality associated with drugs used to treat depression and to examine specific clinical effects associated with serious outcomes. METHOD: The National Poison Data System, which receives exposure reports from regional poison centers serving the United States, Puerto Rico, and the District of Columbia, was queried for single drug exposures in individuals 12 years and older during the period 2000-2014. Medications included were antidepressants, atypical antipsychotics, anticonvulsants, lithium, and other medications used in the treatment of depression. The main outcomes were the morbidity index (the number of serious outcomes per 1,000 exposures) and the mortality index (the number of fatal outcomes per 10,000 exposures). RESULTS: During this 15-year period, there were 962,222 single substance exposures to the 48 medications studied. Serious outcomes rose 2.26-fold and in linear fashion over the 15 years. While tricyclic and monoamine oxidase inhibitor medications were associated with high morbidity and mortality, several newer agents also appeared hazardous. Lithium, quetiapine, olanzapine, bupropion, and carbamazepine were associated with high morbidity indices. Lithium, venlafaxine, bupropion, quetiapine, olanzapine, ziprasidone, valproic acid, carbamazepine, and citalopram were associated with higher mortality indices. CONCLUSIONS: Serious outcomes after overdose or nonintentional exposures to medications used to treat depression have risen dramatically over the past 15 years. The present data suggest that the morbidity and mortality risks vary substantially among these medications. These differences become important when selecting treatments for patients with depression, especially those at increased risk for suicide1206930 field[33]: Not in File B?XNewmeyer, M.N. Swortwood, M.J. Taylor, M.E. Abulseoud, O.A. Woodward, T.H. Huestis, M.A.2017Evaluation of divided attention psychophysical task performance and effects on pupil sizes following smoked, vaporized and oral cannabis administrationJournal of Applied Toxicology#online early: doi: 10.1002/jat.3440not published, 20 Feb 17As Attention BLOOD blood concentration CANNABIS CHRONIC CONCENTRATIONS Consumption DETECTION dose DRIVING driving under the influence DRUG drugs edible EVALUATION HEALTH IMPAIRMENT IS limits Modified Odds Ratio ORAL PLACEBO policy PUBLIC PUBLIC HEALTH Pupil tetrahydrocannabinol THC Time 1/31/2017<Establishing science-based driving per se blood Delta9 -tetrahydrocannabinol (THC) limits is challenging, in part because of prolonged THC detection in chronic, frequent users. Therefore, documenting observable signs of impairment is important for driving under the influence of drugs. We evaluated frequent and occasional cannabis smokers' performance on the modified Romberg balance, one leg stand (OLS), and walk and turn (WAT) tasks, and pupil size effects following controlled placebo (0.001% THC), smoked, vaporized and oral (6.9% [~50.4 mg] THC) cannabis administration. Significant effects following inhaled doses were not observed due to delayed tasks administration 1.5 and 3.5 h post-dose, but significant impairment was observed after oral dosing (blood THC concentrations peaked 1.5-3.5 h post-dose). Occasional smokers' odds of exhibiting >/=2 clues on the OLS or WAT following oral dosing were 6.4 (95% CI 2.3-18.4) times higher than after placebo, with THC and 11-hydroxy-THC blood concentrations individually producing odds ratios of 1.3 (1.1-1.5) and 1.5 (1.3-1.8) for impairment in these tasks, respectively. Pupil sizes after oral dosing under the direct lighting condition were significantly larger than after placebo by mean (SE, 95% CI) 0.4 (0.1, 0.2-0.6) mm at 1.5 h and 0.5 (0.2, 0.2-0.8) mm at 3.5 h among all participants. Oral cannabis administration impaired occasional cannabis users' performance on the OLS and WAT tasks compared to placebo, supporting other reports showing these tasks are sensitive to cannabis-related impairment. Occasional smokers' impairment was related to blood THC and 11-hydroxy-THC concentrations. These are important public health policy findings as consumption of edible cannabis products increases. Published 2017. This article is a U.S. Government work and is in the public domain in the USA120775" field[33]: Not in File uB?]Newmeyer, M.N. Swortwood, M.J. Andersson, M. Abulseoud, O.A. Scheidweiler, K.B. Huestis, M.A.2017Cannabis edibles: blood and oral fluid cannabinoid pharmacokinetics and evaluation of oral fluid screening devices for predicting delta9-tetrahydrocannabinol in blood and oral fluid following cannabis brownie administration Clin Chem/online early: doi: 10.1373/clinchem.2016.265371not published, 28 Feb 17ANALYTICAL As BLOOD CANNABINOID cannabinoids CANNABIS CONCENTRATIONS Confirmation Content CRASH DATA DETECTION edible EVALUATION Intake IS KINETICS NO ORAL oral fluid pharmacokinetic PHARMACOKINETICS SCREENING Sensitivity TEST THC Time 2/10/2017BACKGROUND: Roadside oral fluid (OF) Delta9-tetrahydro-cannabinol (THC) detection indicates recent cannabis intake. OF and blood THC pharmacokinetic data are limited and there are no on-site OF screening performance evaluations after controlled edible cannabis. CONTENT: We reviewed OF and blood cannabinoid pharmacokinetics and performance evaluations of the Draeger DrugTest(R)5000 (DT5000) and Alere DDS(R)2 (DDS2) on-site OF screening devices. We also present data from a controlled oral cannabis administration session. SUMMARY: OF THC maximum concentrations (Cmax) were similar in frequent as compared to occasional smokers, while blood THC Cmax were higher in frequent [mean (range) 17.7 (8.0-36.1) mug/L] smokers compared to occasional [8.2 (3.2-14.3) mug/L] smokers. Minor cannabinoids Delta9-tetrahydrocannabivarin and cannabigerol were never detected in blood, and not in OF by 5 or 8 h, respectively, with 0.3 mug/L cutoffs. Recommended performance (analytical sensitivity, specificity, and efficiency) criteria for screening devices of >/=80% are difficult to meet when maximizing true positive (TP) results with confirmation cutoffs below the screening cutoff. TPs were greatest with OF confirmation cutoffs of THC >/=1 and >/=2 mug/L, but analytical sensitivities were <80% due to false negative tests arising from confirmation cutoffs below the DT5000 and DDS2 screening cutoffs; all criteria were >80% with an OF THC >/=5 mug/L cutoff. Performance criteria also were >80% with a blood THC >/=5 mug/L confirmation cutoff; however, positive OF screening results might not confirm due to the time required to collect blood after a crash or police stop. OF confirmation is recommended for roadside OF screening120866. field[33]: Not in File ?+Nikitin, D. Timberlake, D.S. Williams, R.S.2016dIs the e-liquid industry regulating itself? A look at e-liquid internet vendors in the United States 1967-1972Nicotine and Tobacco Research18108ACCIDENTAL ADULT Age Aged As Association author BYPASS case E CIGARETTE E Cigarettes E-CIGARETTE e-Cigarettes e-liquid FDA HEALTH Ingredient INTERNET IS method methods NICOTINE PACKAGING POISONING poisonings Population Regulation RESEARCH restrictions SAFETY STUDY TOBACCO UNITED STATES US use warning labels WHO2016l Introduction: The objective of this study was to assess whether the nascent, but rapidly growing e-liquid industry prohibits Internet sales to minors and employs safety measures to prevent accidental poisonings. Methods: A stratified simple random sample (n = 120) was selected from the target population (N = 1107) of US online vendors of e-liquid in July 2015. The vendors were stratified and subsequently oversampled by trade association membership and vendor popularity. Three minors aged 16 to 17, who were supervised by adult research staff, attempted to purchase e-liquid from the 120 online vendors using debit cards issued in their names. Measures included vendors' use of age verification, warning labels on e-liquid bottles, and child-resistant packaging. Results: Statistically significant differences were observed by vendor popularity, but not by membership in a trade association. The differences by vendor popularity, however, occurred for measures that were limited to an age warning and list of ingredients. The most striking finding was the scant vendors (n = 4) who successfully prevented the sale of e-liquid to the minors. In contrast, 87.5% and 53.9% of the bottles contained child-resistant packaging and a health warning label, respectively. Conclusions: Irrespective of trade association membership or vendor popularity, online vendors of e-liquids are not taking the proper precautions in preventing sales to minors. The FDA's upcoming deeming rules on e-cigarette products should include explicit requirements for offline and online e-liquid vendors, particularly the use of effective age verification, warning labels, and child-resistant packaging. Implications: This study demonstrates that, in the absence of any current FDA regulation of e-liquid products, self-regulation among vendors is not effective in preventing product acquisition by minors. Lax oversight of the e-liquid industry may draw consumers to bypass current tobacco control restrictions implemented in face-to-face sales settings. As a consequence, there may be an increase in online sales to minors. Further regulation of the industry may increase the already prevalent use of child-resistant packaging, leading to fewer cases of accidental nicotine poisoning. Copyright © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved120801$ field[33]: Not in Fileo?Nirupama, K. Renuka, S.2016JHypertropic and exotropic strabismus fixus following neurotoxic snake bite 1309-1310Neurology India646ZACETYLCHOLINE ACETYLCHOLINE RECEPTOR Affect ANTICHOLINESTERASE ANTIVENOM ARREST As Association case COBRA DEPRESSION DISSOCIATION ENVENOMATION evolution EYE FEMALE FIBROSIS Fixed history ICU INFLAMMATION INTENSIVE CARE intensive care unit IS LETTER motor MUSCLE NERVE NEUROLOGICAL neurotoxic NEUROTOXICITY Neurotoxin neurotoxins NEUROTRANSMITTER nicotinic acetylcholine receptors Occurrence OCULAR OPHTHALMIC OPHTHALMOPLEGIA PARALYSIS PATIENT POSTURE RECEPTORS recovery Release RESPIRATORY RESPIRATORY ARREST snake bite SPECIES TEST THERAPY Toxicities TOXICITY toxin TRAUMA TREATMENT UNIT Visual Acuity2016120799* field[33]: year=2016 volume=64 issue=6 spage=1309 epage=1310 aulast=Nirupama Not in File ? QNistor, N. Jitareanu, C. Frasinariu, O.E. Ciomaga, I.M. Rugina, A.L. Streanga, V.2017PEpidemiologic profile and triggering factors of voluntary poisoning in teenagerse5831Medicine (Baltimore)965xACETAMINOPHEN ADOLESCENT Adolescents ALCOHOL As boys case COMA DATA DATABASE DEATH DEPRESSION DRUG drugs Emergencies emergency epidemiologic epidemiological EPIDEMIOLOGY family FATAL Girls Glasgow Coma Scale HOSPITAL INTOXICATION IS NO P PATIENT POISONING poisonings PSYCHOLOGICAL Recurrence Retrospective study RISK Risk factor RISK FACTORS SCALE School SOCIAL STUDY Time use2/2017TSelf-poisoning is an important medical and social problem in adolescents.We performed an observational cross-sectional retrospective study on a group of 219 adolescents admitted for voluntary intoxications at "St. Mary" Children's Emergency Hospital, Iasi during 1 year period. Epidemiological aspects and triggering factors have been analyzed. Data collected from the patients' files were centralized in an SPSS 18.0 database and processed with confidence interval of 95%.We found that pharmaceutical drugs have been usually involved (34.7%), mostly in girls (56.3% vs. 15.5%; P = 0.0001). The most frequently cited reason for poisoning was family conflict, with a relative risk (RR) 1.43 times higher in girls, as well as scholar conflict (RR = 1.39). A great percentage of the monitored girls presented severe depression (23.3% vs. 6.9%; P = 0.001), with an RR more than 3 times higher than in the case of boys. All cases evolved favorably, no death having been recorded, even if 18 teenagers initially presented an extremely serious condition, being admitted in various stages of coma (Glasgow coma scale score < 8).We found that self-inflicted poisonings with pharmaceutical drugs was more common in girls and the use of drug and alcohol intoxication was found especially in boys. The most common pharmaceutical drug involved in self-poisoning was acetaminophen. Psychological disorders and family or school conflicts are the most important triggering factors of voluntary poisoning. Risk factors should be identified after stabilizing the patient, and actions should be taken in order to prevent a fatal recurrence120795- field[33]: Not in File 3?!oNocito Echevarria, M.A. Andrade Reis, T. Ruffo Capatti, G. Siciliano Soares, V. da Silveira, D.X. Fidalgo, T.M.2017EN-acetylcysteine for treating cocaine addiction - A systematic review197-203Psychiatry Research251{acetylcysteine ADDICTION agent ANIMAL animal models As CELL CLINICAL clinical studies Clinical study COCAINE cocaine dependence craving DATA dependence dose EXPERIMENTAL experimental studies glutamate Homeostasis IS LEVELS Long term Long-term MODEL N-ACETYLCYSTEINE NAC PAPER PATIENT PLACEBO PREVENTION RECEPTORS REVIEW STUDY systematic review THERAPEUTIC TREATMENT TRIAL use WHO 2/11/2017The aim of this paper is to extensively review the current literature available on N-acetylcysteine (NAC) treatment for cocaine dependence (clinical and experimental studies). We screened all articles published before February 2016 reporting on the use of NAC as a pharmacological intervention for cocaine dependence or discussed its potential as a therapeutic approach for cocaine dependence. We described our results qualitatively. 21 studies matched our search criteria: 6 clinical trials and 15 animal studies. Four clinical studies showed NAC's capacity to reduce craving, desire to use cocaine, cocaine-cue viewing-time and cocaine-related spending. Studies in animal models also support this reinstatement prevention application of NAC. NAC reverses the disruption of glutamate homeostasis caused by long-term cocaine use restoring function of the cystine-glutamate exchanger in glial cells and reversing the downregulated GLT-1 receptor. Current data suggest promising potential for NAC as an anti-relapse agent, as a double-blind placebo trial was mainly negative, except in the subgroup of patients who were already abstinent. An optimal dose for relapse prevention may be one that restores extrasynaptic glutamate to physiological levels and predominantly activates mGluR2 and 3, but not mGluR5 receptors, which are linked to relapse. NAC may be better suited for avoiding relapse in already abstinent subjects1210960 field[33]: Not in Fileg?"aNozawa, H. Minakata, K. Yamagishi, I. Hasegawa, K. Wurita, A. Gonmori, K. Suzuki, O. Watanabe, K.2015jMALDI-TOF mass spectrometric determination of eight benzodiazepines with two of their metabolites in blood150-156Legal Medicine173!ACID ANALYTICAL As Benzodiazepine BENZODIAZEPINES biological BLOOD case CINNAMIC ACID DETECTION determination DRUG drugs FLUNITRAZEPAM FORENSIC high throughput internal standard LASER Limit of Detection METABOLITE Metabolites method quantification SCREENING SPECTROMETRY ZOLPIDEM ZOPICLONE2015A rapid and sensitive method was developed for the determination of benzodiazepines and benzodiazepine-like substances (BZDs) by matrix-assisted laser desorption ionization (MALDI)-time-of-flight (TOF)-mass spectrometry (MS). In this method, alpha-cyano-4-hydroxy cinnamic acid was used as the matrix to assist the ionization of BZDs. Determination of 8 BZDs (with two of their metabolites) belonging to top 12 medical drugs detected in poisonous cases in Japan, was performed using diazepam-d5 as the internal standard. The limit of detection of zolpidem was 0.07ng/ml with its quantification range of 0.2-20ng/ml in blood, in the best case, and the limit of detection of flunitrazepam was 2ng/ml with its quantification range of 6-200ng/ml in blood, in the worst case. The spectra of zopiclone in MALDI-MS and MS/MS were different from those in electrospray ionization MS and MS/MS. Present method provides a simple and high throughput method for the screening of these BZDs using only 20mul of blood. The developed method was successfully used for the determination of BZDs in biological fluids obtained from two victims. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved1207940\RefMgr field[33]: Not in File ?#0O'Connell, C. Ziniel, S. Hartwell, L. Connor, J.2017yManagement of opioid and sedative weaning in pediatric congenital heart disease patients: assessing the state of practice116-124#Dimensions of Critical Care Nursing362ACUTE acute poisoning Adverse ADVERSE EFFECTS analysis As ASSESSMENT CARDIAC CLINICAL CLONIDINE Content DATA Development DISEASE Frequency Guidelines HEART HOME HOSPITAL IS LORAZEPAM MANAGEMENT METHADONE method methods NURSING OPIOID Opioids PAEDIATRIC Pathway PATIENT pediatric POISONING Qualitative RESPONSE RATE Sedatives STUDY SURVEY SYMPTOMS TREATMENT UNITED STATES use WITHDRAWAL Withdrawal symptoms3/2017BACKGROUND: Opioid and sedative medications are commonly used to treat pediatric patients with congenital heart disease; however, their use is not without adverse effects. Symptoms of withdrawal can occur if the medications are discontinued abruptly or weaned too quickly. OBJECTIVE: The aim of this study was to understand and describe the current management of opioid and sedative weaning in pediatric congenital heart disease patients in freestanding children's hospitals across the United States. METHODS: A Web-based survey of pediatric congenital heart centers was conducted. Survey participants were recruited from the Consortium of Congenital Cardiac Care-Measurement of Nursing Practice. Quantitative data were summarized using frequency and proportions. Qualitative data were summarized using content analysis. RESULTS: Twelve sites participated in the survey (44% response rate). Methadone was used as a weaning medication at 100% of participating sites, lorazepam at 83% of sites, and clonidine at 75% of sites. Seventy-five percent of sites reported using a clinical assessment tool to monitor withdrawal symptoms. Twenty-five percent of sites used a standardized clinical pathway when weaning opioid and sedative medications. Eighty-three percent of sites will consider discharging a patient to complete the medication wean at home. DISCUSSION: Weaning practices varied across sites. While some similarities were observed among sites, substantial practice variation exists. The majority of sites used a clinical assessment tool to assess for withdrawal symptoms. Few sites reported using a standardized approach to weaning patients. Discharging patients to complete an opioid or sedative wean at home was common practice. Opportunities exist for the development of weaning practice guidelines120763. field[33]: Not in FileB?$2O'Connor, T.M. Cusack, R. Landers, S. Bredin, C.P.2014Holy Saturday asthmaBMJ Case Reportsdoi:10.1136/bcr-2014-203861ACID AIRWAY ASTHMA chemical COLOPHONY Cough DIAGNOSIS DYSPNOEA EXPOSURE Forced Expiratory Volume FUMES HI HISTAMINE INHALATION inhalation challenge test IS LATE Man MECHANISM OCCUPATIONAL occupational asthma PATIENT Reduction REVIEW S SERVICE SYMPTOMS TEST Volume2014PA 61-year-old man complained of cough and dyspnoea after exposure to colophony-containing solder fumes at work. A histamine challenge test confirmed airway hyper-responsiveness, and colophony-challenge demonstrated a 16.7% drop in peak expiratory flow rate (PEFR), supporting a diagnosis of colophony-induced occupational asthma. At review, the patient presented with cough, dyspnoea and wheeze that occurred acutely when exposed to the fumes from burning incense during Easter Saturday services, necessitating his departure from the church. Inhalation challenge tests using two blends of incense used at his church (Greek and Vatican) led to identical symptoms and a significant reduction in forced expiratory volume in 1 s 15 min after exposure and PEFRs up to 48 h after exposure, indicating an early and late phase asthmatic reaction. This is the first report of coexistent colophony and incense-induced asthma. The similarities in chemical structures between abietic acid in colophony and boswellic acid in incense suggest a common mechanism. Copyright 2014 BMJ Publishing Group. All rights reserved120702) field[33]: Not in File ?%`Ok, S.-H. Lee, S.H. Kwon, S.-C. Choi, M.H. Shin, I.-W. Kang, S. Park, M. Hong, J.-M. Sohn, J.-T.2017A lipid emulsion reverses toxic-dose bupivacaine-induced vasodilation during tyrosine phosphorylation-evoked contraction in isolated rat aortae394+International Journal of Molecular Sciences182Anesthetic BUPIVACAINE CALCIUM CELL dose ERK IN VITRO INDUCTION Inhibition IS LIPID Lipid emulsion LIPID EMULSION THERAPY MECHANISM MODEL MUSCLE Pathway PROTEIN RAT SENSITIZATION SODIUM solubility STUDY THERAPY toxic VASCULAR 2/13/2017The goal of this in vitro study was to examine the effect of a lipid emulsion on toxic-dose bupivacaine-induced vasodilation in a model of tyrosine phosphatase inhibitor sodium orthovanadate-induced contraction in endothelium-denuded rat aortae and to elucidate the associated cellular mechanism. The effect of a lipid emulsion on vasodilation induced by a toxic dose of a local anesthetic during sodium orthovanadate-induced contraction was examined. In addition, the effects of various inhibitors, either bupivacaine alone or a lipid emulsion plus bupivacaine, on protein kinase phosphorylation induced by sodium orthovanadate in rat aortic vascular smooth muscle cells was examined. A lipid emulsion reversed the vasodilation induced by bupivacaine during sodium orthovanadate-induced contraction. The lipid emulsion attenuated the bupivacaine-mediated inhibition of the sodium orthovanadate-induced phosphorylation of protein tyrosine, c-Jun NH(2)-terminal kinase (JNK), myosin phosphatase target subunit 1 (MYPT1), phospholipase C (PLC) gamma-1 and extracellular signal-regulated kinase (ERK). These results suggest that a lipid emulsion reverses toxic-dose bupivacaine-induced vasodilation during sodium orthovanadate-induced contraction via the activation of a pathway involving either tyrosine kinase, JNK, Rho-kinase and MYPT1 or tyrosine kinase, PLC gamma-1 and ERK, and this reversal is associated with the lipid solubility of the local anesthetic and the induction of calcium sensitization121026& field[33]: Not in File -?&UOldham, M.J. Wagner, K.A. Gilman, I.G. Beach, J.B. Liu, J. Rostami, A.A. Sarkar, M.A.2017oDevelopment/verification of methods for measurement of exhaled breath and environmental e-vapor product aerosol55-63$Regulatory Toxicology & Pharmacology85ACETALDEHYDE ACETONE ACROLEIN Aerosol AEROSOLS AIR analysis ANALYTICAL analytical methods As BENZENE BREATH E CIGARETTE E Cigarettes E-CIGARETTE e-Cigarettes e-liquid E-vapor ENVIRONMENTAL ETHYLBENZENE EXPOSURE FORMALDEHYDE HEALTH Health effects ISOPRENE LEVELS Measurement METALS method methods METHYL ETHYL KETONE NICOTINE ORGANIC PROPYLENE PROPYLENE GLYCOL quantification TOLUENE use 1/30/2017eConcerns have been raised about the potential health effects of potential bystander exposure to exhaled aerosols from e-vapor products (EVPs). An exhaled breath collection system (EBS) was developed and analytical methods were verified for collection and analysis of exhaled breath from users of EVPs. Analytical methods were adapted and verified for collection of environmental air samples during EVP use in an exposure chamber. Analysis of constituents in exhaled breath focused on nicotine, propylene glycol, and glycerin (because these are reported as the major constituents in EVPs) and selected carbonyl compounds (acetaldehyde, acrolein, and formaldehyde). Analysis of environmental samples included nicotine, propylene glycol, glycerin, 12 volatile organic compounds (VOCs), 15 carbonyl compounds and 4 metals. The EBS and analytical methods used were found to be suitable for collection and analysis of the target constituents in exhaled breath. Environmental sampling for background levels of VOCs and carbonyl compounds found only acetone, acetaldehyde, benzene, ethylbenzene, formaldehyde, isoprene, methyl ethyl ketone, hexaldehyde, propionaldehyde, and toluene above the limit of quantification in some samples. None of the targeted metals were detected. Background levels of VOCs and carbonyl compounds were consistent with levels previously reported for ambient air120807- field[33]: Not in File B?'Olympio, K.P. Gonçalves, C.G. Salles, F.J. da Silva Ferreira, A.P.S. Soares, A.S. Buzalaf, M.A.R. Cardoso, M.R.A. Bechara, E.J.H.2017UWhat are the blood lead levels of children living in Latin America and the Caribbean?Environment International/online early: doi: 10.1016/j.envint.2016.12.022not published, 16 Feb 17nAge Aged ANALYTICAL Association BLOOD Blood lead Canada CHILDREN DATA DATABASE Emission source EXPOSURE HEALTH IDENTIFICATION INFORMATION IS LEAD Lead exposure Lead Poisoning LEVELS LITERATURE REVIEW method Mexico NO OCCUPATIONAL PAEDIATRIC PAPER POISONING policy PORTUGUESE prevalence PREVENTION PUBLIC PUBLIC HEALTH REVIEW RISK S Source SPANISH STUDY UNITED STATES2/1/2017INTRODUCTION: Information on the prevalence of lead exposure is essential to formulate efficient public health policies. Developed countries have implemented successful public policies for the prevention and control of lead poisoning. In the United States, Canada, Japan and the European Union, for instance, periodically repeated prevalence studies show that blood lead levels (BLLs) in children have decreased overall. Although BLL of Latino children in the U.S. have also dropped in recent years, the geometric mean remains higher than that of white children. Little is known about lead exposure in children in Latin America and the Caribbean (LAC). In this review, we responded to two questions: What is currently known about lead sources and levels in children in LAC? Are there public policies to prevent children's exposure to lead in LAC? METHOD: We conducted a literature review covering the period from January 2000 to March 2014 in the PubMed and Lilacs databases to obtain English, Portuguese and Spanish language studies reporting the prevalence of BLLs in children aged 0-18years living in LAC countries. No specific analytical method was selected, and given the scarcity of data, the study was highly inclusive. RESULTS: Fifty-six papers were selected from 16 different LAC countries. The children's BLLs found in this review are high (>/=10mug/dL) compared to BLLs for the same age group in the U. S. However, most studies reported an association with some type of "lead hot spot", in which children can be exposed to lead levels similar to those of occupational settings. Only Peru and Mexico reported BLLs in children from population-based studies. CONCLUSIONS: Most BLLs prevalence studies carried out in LAC were in areas with known emission sources. The percentage of children at risk of lead poisoning in LAC is unknown, and probably underestimated. Thus, there is an urgent need to establish public health policies to quantify and prevent lead poisoning, specifically by prioritizing the identification and control of "hot spots"120764. field[33]: Not in File D?(-Oruch, R. Pryme, I.F. Engelsen, B.A. Lund, A.2017INeuroleptic malignant syndrome: an easily overlooked neurologic emergency161-175&Neuropsychiatric Disease and Treatment13active metabolite Age agent Antipsychotic antipsychotics As Awareness CALCIUM case CLINICAL Cold complications DIAGNOSIS DOPAMINE dose DRUG Emergencies emergency FEMALE genetic GENETICS HYPERPYREXIA IATROGENIC INTENSIVE CARE INTRAVENOUS IS Laboratories LABORATORY laboratory tests LEAD lethal MALE MALIGNANT MENTAL STATUS METABOLITE Metabolites MORBIDITY MORTALITY NEUROLEPTIC MALIGNANT SYNDROME neuron NEUROTOXICITY Observation PATHOPHYSIOLOGY PATIENT Release REMOVAL SEVERITY STATUS Syndrome TEST TREATMENT use2017Neuroleptic malignant syndrome is an unpredictable iatrogenic neurologic emergency condition, mainly arising as an idiosyncratic reaction to antipsychotic agent use. It is characterized by distinctive clinical features including a change in mental status, generalized rigidity, hyperpyrexia, and dysautonomia. It can be lethal if not diagnosed and treated properly. Mortality and morbidity attributed to this syndrome have recently declined markedly due to greater awareness, earlier diagnosis, and intensive care intervention. In most cases, the syndrome occurs as a result of a rapid increase in a dose of neuroleptic, especially one of the long-acting ones. Pathophysiology behind this syndrome is attributed to a dopamine receptor blockade inside the neurons rendered by the offending drug and excessive calcium release from the sarcoplasmic reticulum of skeletal myocytes. Laboratory tests, although not diagnostic, may assist in assessing the severity of the syndrome and also the consequent complications. The syndrome has been described in all age groups and occurs more in males than in females. Genetics appears to be central regarding the etiology of the syndrome. Stopping the use of the offending agent, cold intravenous fluids, and removal of the causative agent and its possible active metabolites is the cornerstone of treatment. Periodic observation of psychotic patients recently started on antipsychotic medications, especially those being treated with depot preparations, may aid to an early diagnosis of the syndrome and lead to early treatment120800% field[33]: Not in FileB?)@Osborne, N.J. Cairns, R. Dawson, A.H. Chitty, K.M. Buckley, N.A.2017EEpidemiology of coronial deaths from pesticide ingestion in Australia9International Journal of Hygiene and Environmental early: doi: 10.1016/j.ijheh.2017.01.009not published, 01 Mar 17Affect AGRICULTURAL As Australia case DEATH Deaths DISTRIBUTION EPIDEMIOLOGY INGESTION IS MALE MISUSE pesticide PESTICIDES POISONING poisonings Population STATUS STUDY SUICIDE2/4/2017Pesticides in Australia are tightly regulated but it is unknown how this may affect the distribution of misuse and self-harm across Australia, both spatially and within subgroups in the population. We performed an observational study to examine spatial differences in suicide/deliberate poisonings with pesticides in Australia. We examined Coronial inquest cases of self-harm by pesticide ingestion for the years 2001-2013 (n=209). Coronial cases were older, more likely to be male, have lower SES status and live in outer regional areas as opposed to cities when compared to the general population. Case densities (cases/100,000 population) were lower in large capital cities and higher in agricultural areas: despite this half the cases occurred in major cities121024- field[33]: Not in FileE?*J8Osinaike, B.B. Oranusi, I.O. Akinyemi, O.A. Sanusi, A.A.2013jIntensive care management of organophosphate poisoned patient: a test of critical care services in Nigeria50-54Annals of African Surgery1020ACUTE acute poisoning ANTIDOTE ATROPINE central nervous system CHOLINERGIC CRITICAL CARE Environment FACILITIES history ICU INGESTION INSECTICIDE INTENSIVE CARE INTRAVENOUS IS MALE MANAGEMENT Nigeria op organophosphate Organophosphates Oxime PAPER PATIENT POISONING PRALIDOXIME SERVICE TEST TREATMENT WHO2013The management of organophosphate poisoning is challenging, more so in the setting of poor critical care facilities. The management requires the administration of atropine, an antidote (oxime) and supportive care often provided in the ICU. We report a 35year old male who presented with a history of ingestion of an organophosphate insecticide and features of cholinergic and central nervous system affectation. The patient was managed with intravenous atropine, pralidoxime, ventilator support and other supportive care. This paper highlights those challenges associated with the management of organophosphate poisoning in our environment120818; Not in File B?+<Pajoumand, A. Zamani, N. Hassanian-Moghaddam, H. Shadnia, S.2017Can duration of hemodialysis be estimated based on the on-arrival laboratory tests and clinical manifestations in methanol-poisoned patients?$International Urology and Nephrology,online early: doi: 10.1007/s11255-017-1521-2not published, 28 Feb 17MALCOHOL analysis As BICARBONATE CLINICAL CREATININE DIALYSIS dose duration Dyspnea EFFICACY ETHANOL HAEMODIALYSIS hemodialysis ingested IS Laboratories LABORATORY laboratory tests LEUCOVORIN LEVELS METHANOL method methods P PATIENT PREDICTION Regression Analysis Retrospective study SERUM STUDY TEST Time TREATMENT US Vital signs WHO2/6/2017PURPOSE: We aimed to evaluate the efficacy of Lachance formula and more readily available clinical or laboratory factors (other than serum methanol level) in prediction of the needed time for hemodialysis in methanol-poisoned patients. METHODS: In a retrospective study, all methanol-poisoned patients referred to us between March 2008 and March 2016 were enrolled. The patients' demographic characteristics, on-arrival vital signs, signs/symptoms, and laboratory tests were evaluated for factors that could prognosticate the dialysis duration. RESULTS: Of 72 patients enrolled, 54 underwent hemodialysis once (group 1) and 18 needed more than one session of hemodialysis (group 2). All were treated by ethanol, bicarbonate, and leucovorin. Lachance formula overestimated the patients in higher methanol levels and underestimated them in lower methanol levels. It properly predicted the needed time for hemodialysis when the methanol level was between 15 and 25 mg/dL. Groups 1 and 2 were different in terms of their ingested alcohol dose (P = 0.001), creatinine (P = 0.02), dyspnea on presentation (P = 0.002), and the place they had been dialyzed (P = 0.013). Dialysis duration significantly correlated with dyspnea on presentation (P = 0.028) and ingested alcohol dose (P = 0.02). After performance of logistic regression analysis, only creatinine was statistically significantly different between the two groups (P = 0.02). Median creatinine levels were 1.3 [1, 6] (0.8-2.7) and 1.4 [1.35, 2.1] (0.8-6.5) in the patients who were dialyzed once and twice, respectively. CONCLUSIONS: As a conclusion, creatinine is possibly a readily available test that can predict the appropriate time needed for hemodialysis in methanol-poisoned patients120890+ field[33]: Not in File %?,0Palaszewska-Tkacz, A. Czerczak, S. Konieczko, K.2017cChemical incidents resulted in hazardous substances releases in the context of human health hazards95-110<International Journal of Occupational & Environmental Health301ACID AMMONIA analysis As ASSESSMENT case chemical CHEMICAL INCIDENT CHILDREN DATA DATA COLLECTION determination Emergencies emergency Environment EXPOSURE fatalities fatality HAZARD hazardous HEALTH Health hazard health hazards Health risk Health risk assessment HUMAN Human exposure Human health HYDROCHLORIC ACID IDENTIFICATION INDUSTRIAL INFORMATION IS LEAD Liquids METHANE method methods NO Population POTASSIUM POTASSIUM HYDROXIDE Qualitative Regression Analysis Release RESEARCH RISK RISK ASSESSMENT SERVICE SODIUM Time toxic 2/21/2017OBJECTIVES: The research purpose was to analyze data concerning chemical incidents in Poland collected in 1999-2009 in terms of health hazards. MATERIAL AND METHODS: The data was obtained, using multimodal information technology (IT) system, from chemical incidents reports prepared by rescuers at the scene. The final analysis covered sudden events associated with uncontrolled release of hazardous chemical substances or mixtures, which may potentially lead to human exposure. Releases of unidentified substances where emergency services took action to protect human health or environment were also included. RESULTS: The number of analyzed chemical incidents in 1999-2009 was 2930 with more than 200 different substances released. The substances were classified into 13 groups of substances and mixtures posing analogous risks. Most common releases were connected with non-flammable corrosive liquids, including: hydrochloric acid (199 cases), sulfuric(VI) acid (131 cases), sodium and potassium hydroxides (69 cases), ammonia solution (52 cases) and butyric acid (32 cases). The next group were gases hazardous only due to physico-chemical properties, including: extremely flammable propane-butane (249 cases) and methane (79 cases). There was no statistically significant trend associated with the total number of incidents. Only with the number of incidents with flammable corrosive, toxic and/or harmful liquids, the regression analysis revealed a statistically significant downward trend. The number of victims reported was 1997, including 1092 children and 18 fatalities. CONCLUSIONS: The number of people injured, number of incidents and the high 9th place of Poland in terms of the number of Seveso establishments, and 4 times higher number of hazardous industrial establishments not covered by the Seveso Directive justify the need for systematic analysis of hazards and their proper identification. It is advisable enhance health risk assessment, both qualitative and quantitative, by slight modification of the data collection system so as to enable the determination of released chemical concentration and exposed populations. Int J Occup Med Environ Health 2017;30(1):95-110121029* field[33]:,61372,0,2.html Not in File B?-!Palmer, E. Hart, S. Freeman, P.R.2017aDevelopment and delivery of a pharmacist training program to increase naloxone access in Kentucky2Journal of the American Pharmaceutical Association-online early: doi: 10.1016/j.japh.2016.12.071not published, 21 Feb 17As Association College DEATH Development dispensing EDUCATION HEALTH IDENTIFICATION INFORMATION NALOXONE OPIOID Opioid overdose OVERDOSE PATIENT PHARMACOLOGY PREVENTION PROTOCOL PUBLIC PUBLIC HEALTH ranking Regulation REGULATIONS SCREENING STATUS use WHO2/1/2017JOBJECTIVE: To describe the development and delivery of a comprehensive training program for Kentucky pharmacists to enable dispensation of naloxone per protocol. PRACTICE DESCRIPTION: In May 2015, the Kentucky Board of Pharmacy (KBP) promulgated regulations outlining the requirements for pharmacists to initiate the dispensing of naloxone under a physician-approved protocol. The Advancing Pharmacy Practice in Kentucky Coalition, a partnership between Kentucky's Colleges of Pharmacy, KBP, and state and local pharmacists associations, developed and offered educational programming to fulfill this regulation. Pharmacists who completed the 90-minute program could apply to KBP for registration as a naloxone-certified pharmacist. The program consists of a 90-minute session covering naloxone access, opioid overdoses, the pharmacology and use of naloxone, protocol development, patient identification, and resources. Sessions were offered live and via webinar. Sessions have also been incorporated into the pharmacy curriculum at the 2 colleges of pharmacy in Kentucky. RESULTS: Between June 28, 2015, and June 1, 2016, a total of 1254 pharmacists and 348 student pharmacists completed training. Of those, 646 (52%) have applied to KBP and received naloxone-certified status. The program was well received, with 87% of learners ranking the usefulness of the information presented as excellent. Learners cited screening tips, protocol information, patient screening information, and education resources as information they will implement in their practice. CONCLUSION: The swift deployment of training to a wide variety of pharmacy professionals has resulted in a substantial number of naloxone-certified pharmacists across Kentucky. Through a coordinated training initiative involving all major pharmacy stakeholders, we reached many individuals rapidly, documenting the value of this approach for future training endeavors. This educational initiative may enhance pharmacy practice across Kentucky and the nation by expanding and educating on the role pharmacists can play in public health and overdose death prevention120789, field[33]: Not in File ?.Parekh, U. Gupta, S.2017WKerosene-a toddler's sin: a five years study at tertiary care hospital in western India24-28&Journal of Forensic and Legal Medicine47+ACCIDENTAL ACUTE Age As case central nervous system CHILDREN CONTAINERS Cough DATA DEATH Deaths DIAGNOSIS Fever HEALTH HOSPITAL HOUSEHOLD Incidence India INDIUM IS KEROSENE MORBIDITY MORTALITY PAEDIATRIC PNEUMONIA POISONING Population Rural Source STATUS STUDY TERTIARY CARE TREATMENT Urban Vomiting 2/20/2017Acute kerosene poisoning is a preventable health problem in children perceived mainly in developing countries. It influences socioeconomic and cultural status of country due to its contribution in morbidity and mortality. As kerosene is widely used as household energy source in India at rural areas as well as urban, it accounts for significant number of poisoning cases mainly accidental in manner. As there are only handful studies from India on kerosene poisoning in children, we planned this study to evaluate incidence of kerosene poisoning in Western Indian population and its clinico-epidemiotoxicological profile. In this retrospective cross-sectional study, we collected data of all the cases of kerosene poisoning diagnosed during five years from 2009 to 2013 at Shri Krishna hospital situated at Karamsad, Gujarat state of Western India. We observed among total 42 cases, all victims were under 3 years of age. Evening in summer months, rural areas, storage of kerosene in household containers, inadequate parental supervision and door-to-hospitalization period emerged as most serious associated factors. Fever, cough, vomiting, tachypnoea and leucocytosis were commonest manifestations while pneumonia was the most common complication. Signs of central nervous system involvement, leucocytosis and vomiting were significantly correlated with pneumonia. Deaths occurred due to pneumonia. Early diagnosis and treatment of pneumonia may reduce mortality and recommendations are made to reduce the incidence of kerosene poisoning121047, field[33]: Not in File ?/Patil, G. Murthy, N. Nikhil, M.2016Contributing factors for morbidity and mortality in patients with organophosphate poisoning on mechanical ventilation: a retrospective study in a teaching hospital UC18-UC20+Journal of Clinical and Diagnostic Research1012ACUTE Age AGRICULTURAL As case CHOLINESTERASE CLINICAL DATA DEATH DIAGNOSIS duration history HOSPITAL ICU India INDIUM INTENSIVE CARE intensive care unit IS LEVELS Mechanical ventilation method methods MORBIDITY MORTALITY op organophosphate Organophosphates organophosphorus PATIENT POISONING RESEARCH Retrospective study SERUM SEVERITY STUDY suicidal SYMPTOMS UNIT use VENTILATION WHO2016Introduction: One of the most common causes of poisoning in agricultural based developing countries like India is due to Organophosphorus (OP) compound. Its widespread use and easy availability has increased the likelihood of poisoning with these compounds. Aim: To study the morbidity and mortality in patients with acute OP poisoning requiring mechanical ventilation. Materials and Methods: This was a retrospective study constituting patients of all age groups admitted to the Intensive Care Unit (ICU) with diagnosis of OP poisoning between January 2015 to December 2015. Of 66 OP poisoning cases those patients who went against medical advice, 20 were excluded from the study and thus 46 patients were included. Diagnosis was performed from the history taken either from the patient or from the patient's relatives and presenting symptoms. Demographic data, month of the year, age of patient, mode of poisoning, cholinesterase levels, duration of mechanical ventilation and mortality were recorded. Data are presented as mean +/- SD. Results: A 97.83% (45/46) of cases were suicidal. Out of 46, 9 were intubated and mechanically ventilated. Duration of mechanical ventilation varied from less than 48 hours to more than 7 days. Mortality rate was 50%, 0% and 100% in those who required mechanical ventilation for more than 7 days, 2 to 7 days and <2days respectively. None of the predictors like age, severity of poisoning, cholinesterase levels and duration of ventilation were independent predictors of death and all of them contributed to the mortality. Overall mortality rate in those who required mechanical ventilation was 22.22% Conclusion: Morbidity and mortality due to OP poisoning is directly proportional to the age, severity of poisoning and duration of mechanical ventilation and inversely proportional to serum cholinesterase level. Copyright © 2016, Journal of Clinical and Diagnostic Research. All rights reserved120776. field[33]: Not in File D?0Paz, L.N.F. Moura, L.M. Feio, D.C.A. de Souza Gonçalves Cardoso, M. Ximenes, W.L.O. Montenegro, R.C. Alves, A.P.N. Burbano, R.R. Lima, P.D.L.2017]Evaluation of in vivo and in vitro toxicological and genotoxic potential of aluminum chloride130-137 Chemosphere175:agent ALUMINIUM aluminum analysis As biological BLOOD CELL chemical CONCENTRATIONS COSMETIC Cosmetics CYTOTOXICITY DISTRIBUTION DONOR EVALUATION EXPOSURE FOOD genotoxic IN VITRO IN VIVO IS LESIONS LYMPHOCYTES MICE Micronucleus Micronucleus test NECROSIS Organs PERIPHERAL STUDY TEST toxic Toxicities TOXICITY WATER2/3/2017#Aluminum and its compounds are common contaminants of water and food, as well as medications and cosmetics. The wide distribution of the element facilitates the demand for detailed studies of its biological and toxicological effects. This work aimed to evaluate the possible genotoxic and toxic activity resulting from in vivo and in vitro exposure to Al. For in vivo analysis, 40 Swiss mice were used, various concentrations of hydrated aluminum chloride were administered orally. They were analyzed for possible genic activity and metal cytotoxicity using a micronucleus test (MN), and for toxicity through histopathological evaluation of the extracted organs. For in vitro analysis, lymphocytes from the peripheral blood of 3 healthy donors were used. These cells were exposed to the same chemical agent in various concentrations. In vivo study revealed a significant increase in the number of MN in all Al concentrations. Furthermore, significant alterations in all the organs evaluated were verified by the presence of irreversible lesions (such as necrosis). Corroborating these findings, a significant increase in the quantity of MN in all concentrations with lymphocytes in vitro. In light of this, we suggest that this metal presents genotoxic potential and is potentially a cause of pathological disorders1209653 field[33]: Not in File ?1FPeng, S.-H. Hsu, S.-Y. Kuo, P.-J. Rau, C.-S. Cheng, Y.-A. Hsieh, C.-H.2016hInfluence of alcohol use on mortality and expenditure during hospital admission: a cross-sectional studye013176BMJ Open6111ADULT Age Aged ALCOHOL Alcohol use As BLOOD Blood alcohol concentration CLINICAL Clinical presentation COMA COMPARISON COST DATA GCS Glasgow Coma Scale HOSPITAL HOSPITAL ADMISSION injuries Injury INTOXICATION IS MORTALITY outcome PATIENT Pharmaceuticals Registry SCALE SEVERITY Sex STUDY Taiwan TRAUMA use2016Objectives This study was designed to investigate the effect of alcohol intoxication on clinical presentation of hospitalised adult trauma patients at a Level I trauma centre using propensity score matching. Design Cross-sectional study. Setting Taiwan. Participants Detailed data of 929 hospitalised adult trauma patients with alcohol intoxication, aged 20-65 years, and 10 104 corresponding patients without alcohol intoxication were retrieved from the Trauma Registry System between 1 January 2009 and 31 December 2014. Alcohol intoxication was defined as a blood alcohol concentration (BAC) >50 mg/dL. Main outcome measures In-hospital mortality and expenditure. Results Patients with alcohol intoxication presented with significantly higher short-term mortality (OR: 3.0, 95% CI 2.0 to 4.4; p<0.001) than patients without alcohol intoxication. However, on comparison with propensity score-matched patients with respect to sex, age, comorbidity, Glasgow Coma Scale (GCS), injury region based on Abbreviated Injury Scale (AIS) and Injury Severity Score (ISS), alcohol intoxication did not significantly influence mortality (OR: 0.8, 95% CI 0.5 to 1.4; p=0.563). This implied that the higher mortality of alcohol-intoxicated patients was attributable to patient characteristics such as a higher injury severity rather than alcohol intoxication. Even on comparison with sex-matched, age-matched and comorbidity-matched patients without alcohol intoxication, patients with alcohol intoxication still had significantly higher total expenditure (17.4% higher), cost of operation (40.3% higher), cost of examination (52.8% higher) and cost of pharmaceuticals (38.3% higher). Conclusions The associated higher mortality of adult trauma patients with alcohol intoxication was completely attributable to other patient characteristics and associated injury severity rather than the effects of alcohol. However, patients with alcohol intoxication incurred significantly higher expenditure than patients without alcohol intoxication, even on comparison with sex-matched, age-matched and comorbidity-matched patients without alcohol intoxication. Copyright © 2016 Published by the BMJ Publishing Group Limited120704- field[33]: Not in FileB?2Phillips, J. Lim, F. Hsu, R.20179Synthetic cannabinoid poisoning: a growing health concernNursing Management6online early: doi: 10.1097/01.NUMA.0000512504.16830.b6not published, 28 Feb 17CANNABINOID cannabinoids CANNABIS DESIGNER DRUGS HEALTH NOVEL PSYCHOACTIVE SUBSTANCES POISONING SYNTHETIC CANNABINOID Synthetic cannabinoids2/7/20171209125 field[33]: Not in File?3Pigatto, P.D. Guzzi, G.2017)Allergy to gold: the two faces of mercury105-106Annals of Dermatology291Allergens allergies ALLERGY analysis author DENTAL EXPERIMENTAL GOLD HUMAN Humans HYPERSENSITIVITY interpretation IS IV LETTER MERCURY NICKEL PATCH patch testing PATIENT POTASSIUM REACTIONS SODIUM STUDY sulfate TEST Testing2/2017120944( field[33]: Not in FileB?4^Pillow, T.H. Schutten, M. Yu, S.-F. Ohri, R. Sadowsky, J. Poon, K.A. Solis, W. Zhong, F. Del Rosario, G. Go, M.A. Lau, J. Yee, S. He, J. Liu, L. Ng, C. Xu, K. Leipold, D.D. Kamath, A.V. Zhang, D. Masterson, L. Gregson, S.J. Howard, P.W. Fang, F. Chen, J. Gunzner-Toste, J. Kozak, K.K. Spencer, S. Polakis, P. Polson, A.G. Flygare, J.A. Junutula, J.R.2017Modulating therapeutic activity and toxicity of pyrrolobenzodiazepine antibody-drug conjugates with self-immolative disulfide linkersMolecular Cancer Therapeutics0online early: doi: 10.1158/1535-7163.MCT-16-0641not published, 01 Mar 17ANTIBODIES chemical CYSTEINE DATA dose DRUG drugs EFFICACY HUMAN MICE RAT rats SAFETY STUDY THERAPEUTIC Toxicities TOXICITY tumor use 2/21/2017A novel disulfide linker was designed to enable a direct connection between cytotoxic pyrrolobenzodiazepine (PBD) drugs and the cysteine on a targeting antibody for use in antibody-drug conjugates (ADCs). ADCs composed of a cysteine-engineered antibody were armed with a PBD using a self-immolative disulfide linker. Both the chemical linker and the antibody site were optimized for this new bioconjugation strategy to provide a highly stable and efficacious ADC. This novel disulfide ADC was compared to a conjugate containing the same PBD drug, but attached to the antibody via a peptide linker. Both ADCs had similar efficacy in mice bearing human tumor xenografts. Safety studies in rats revealed that the disulfide-linked ADC had a higher maximum tolerated dose (MTD) than the peptide-linked ADC. Overall, these data suggest that the novel self-immolative disulfide linker represents a valuable way to construct ADCs with equivalent efficacy and improved safety121073/ field[33]: Not in File?5J Pizzorno, J.2016WWhat should we tell our patients about marijuana (Cannabis indica and Cannabis sativa)?8-12Integrative Medicine156ADULT CANNABIS CLINICAL CONTAMINATION DRUG EDITORIAL HEALTH injuries Injury IRRITATION MARIJUANA Medicine Motivation PATIENT pesticide PESTICIDES Recreational use RESEARCH RESIDUE Residues REVIEW SAFETY SOLVENT Toxicities TOXICITY US use WHO12/2016}With several states allowing medicinal use of marijuana and a growing number decriminalizing recreational use, many of our patients are using this herbal drug. Approximately 43% of US adults have tried marijuana, with 13% using it regularly. These users are seeking help from integrative medicine practitioners regarding safety. They are looking for advice based on research and clinical experience, not politics or philosophical bias. The major health problems caused by marijuana appear to be bronchial irritation, decreased motivation, learning difficulties, and injuries. However, less well appreciated are the toxicity problems caused by contamination with pesticides and solvent residues. We have important guidance to help prevent unnecessary toxicity in our patients who choose to use marijuana. This editorial reviews toxicity and safety. Medicinal use will be addressed in the future121031: Not in File B?6WPoet, T.S. Timchalk, C. Bartels, M.J. Smith, J.N. McDougal, R. Juberg, D.R. Price, P.S.2017eUse of a probabilistic PBPK/PD model to calculate data derived extrapolation factors for chlorpyrifos&Regulatory Toxicology and early: doi: 10.1016/j.yrtph.2017.02.014not published, 01 Mar 17ACETYLCHOLINESTERASE active metabolite ADULT analysis As ASSESSMENT BIOCHEMISTRY biological BLOOD CELL chemical CHEMICALS CHLORPYRIFOS Chlorpyrifos oxon CHLORPYRIFOS-OXON CLEARANCE DATA dose EXPOSURE HEALTH Health risk Health risk assessment HUMAN Human exposure Human health Humans impact INFANT Infants Inhibition INSECTICIDE men METABOLITE MODEL op Oxon PHARMACODYNAMICS pharmacokinetic PHYSIOLOGY Population PREDICTION PREGNANCY RISK RISK ASSESSMENT Source uncertainty factor use Variability WOMEN 2/23/20172A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model combined with Monte Carlo analysis of inter-individual variation was used to assess the effects of the insecticide, chlorpyrifos and its active metabolite, chlorpyrifos oxon in humans. The PBPK/PD model has previously been validated and used to describe physiological changes in typical individuals as they grow from birth to adulthood. This model was updated to include physiological and metabolic changes that occur with pregnancy. The model was then used to assess the impact of inter-individual variability in physiology and biochemistry on predictions of internal dose metrics and quantitatively assess the impact of major sources of parameter uncertainty and biological diversity on the pharmacodynamics of red blood cell acetylcholinesterase inhibition. These metrics were determined in potentially sensitive populations of infants, adult women, pregnant women, and a combined population of adult men and women. The parameters primarily responsible for inter-individual variation in RBC acetylcholinesterase inhibition were related to metabolic clearance of CPF and CPF-oxon. Data Derived Extrapolation Factors that address intra-species physiology and biochemistry to replace uncertainty factors with quantitative differences in metrics were developed in these same populations. The DDEFs were less than 4 for all populations. These data and modeling approach will be useful in ongoing and future human health risk assessments for CPF and could be used for other chemicals with potential human exposure121104- field[33]: Not in File @?7'Pope, K. So, Y.T. Crane, J. Bates, M.N.2017FAmbient geothermal hydrogen sulfide exposure and peripheral neuropathy10-15Neurotoxicology60lACUTE Acute toxicity ADULT Aged analysis As Association CHRONIC Chronic exposure CLINICAL CO DATA evidence EXPOSURE Exposure metric GA GAS HYDROGEN hydrogen sulfide HYDROGEN SULPHIDE IS LEVELS MECHANISM method methods NERVE NEUROPATHY NEUROTOXICITY NO PERIPHERAL PERIPHERAL NEUROPATHY Population REFLEX residents Sensitivity STUDY SYMPTOMS TEST Toxicities TOXICITY 2/14/2017The mechanism of toxicity of hydrogen sulfide (H2S) gas is thought mainly to operate through effects on the nervous system. The gas has high acute toxicity, but whether chronic exposure causes effects, including peripheral neuropathy, is yet unclear. The city of Rotorua, New Zealand, sits on an active geothermal field and the population has some of the highest measured ambient H2S exposures. A previous study in Rotorua provided evidence that H2S is associated with peripheral neuropathy. Using clinical methods, the present study sought to investigate and possibly confirm this association in the Rotorua population. The study population comprised 1635 adult residents of Rotorua, aged 18-65. Collected data relevant to the peripheral neuropathy investigation included symptoms, ankle stretch reflex, vibration sensitivity, as measured by the timed-tuning fork test and a Bio-Thesiometer (Bio-Medical Instrument Co., Ohio), and light touch sensitivity measured by monofilaments. An exposure metric, estimating time-weighted H2S exposure across the last 30 years was used. Principal components analysis was used to combine data across the various indicators of possible peripheral neuropathy. The main data analysis used linear regression to examine associations between the peripheral nerve function indicators and H2S exposure. None of the peripheral nerve function indicators were associated with H2S exposure, providing no evidence that H2S exposure at levels found in Rotorua is a cause of peripheral neuropathy. The earlier association between H2S exposure and peripheral neuropathy diagnoses may be attributable to the ecological study design used. The possibility that H2S exposure misclassification could account for the lack of association found cannot be entirely excluded121079- field[33]: Not in File ?8|9Popovska-Gorevski, M. Dubocovich, M.L. Rajnarayanan, R.V.20177Carbamate insecticides target human melatonin receptors574-582Chemical Research in Toxicology302As ca CANCER CARBAMATE INSECTICIDE Carbamate insecticides CARBAMATES CARBARYL CARBOFURAN CELL DATA DIABETES DISEASE EFFICACY HEALTH HUMAN Human health impact in silico INSECTICIDE Insecticides MECHANISM MELATONIN PM RECEPTORS Regulatory SCREENING toxic 2/20/2017Carbaryl (1-naphthyl methylcarbamate) and carbofuran (2,3-dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate) are among the most toxic insecticides, implicated in a variety of diseases including diabetes and cancer among others. Using an integrated pharmacoinformatics based screening approach, we have identified these insecticides to be structural mimics of the neurohormone melatonin and were able to bind to the putative melatonin binding sites in MT1 and MT2 melatonin receptors in silico. Carbaryl and carbofuran then were tested for competition with 2-[125I]-iodomelatonin (300 pM) binding to hMT1 or hMT2 receptors stably expressed in CHO cells. Carbaryl and carbofuran showed higher affinity for competition with 2-[125I]-iodomelatonin binding to the hMT2 compared to the hMT1 melatonin receptor (33 and 35-fold difference, respectively) as predicted by the molecular modeling. In the presence of GTP (100 mM), which decouples the G-protein linked receptors to modulate signaling, the apparent efficacy of carbaryl and carbofuran for 2-[125I]-iodomelatonin binding for the hMT1 melatonin receptor was not affected but significantly decreased for the hMT2 melatonin receptor compatible with receptor antagonist/inverse agonist and agonist efficacy, respectively. Altogether, our data points to a potentially new mechanism through which carbamate insecticides carbaryl and carbofuran could impact human health by altering the homeostatic balance of key regulatory processes by directly binding to melatonin receptors1207610 field[33]: Not in File ?9`Prasad, S. Sajja, R.K. Kaisar, M.A. Park, J.H. Villalba, H. Liles, T. Abbruscato, T. Cucullo, L.2017gRole of Nrf2 and protective effects of metformin against tobacco smoke-induced cerebrovascular toxicity58-69 Redox Biology12ANTICOAGULANT Blood brain barrier Blood-Brain Barrier CIGARETTE Content DATA DIABETES diabetes mellitus DRUG ENDOTHELIAL evidence GLUCOSE IMPAIRMENT INFLAMMATION IS LEVELS MECHANISM Mechanisms METFORMIN NEUROLOGICAL NICOTINE Nrf2 OXIDATIVE STRESS OXYGEN Pathway PROTEIN Reduction RISK ROS SMOKING SPECIES STRESS STROKE TOBACCO Toxicities TOXICITY transporter TREATMENT Type 2 diabetes use VASCULAR 2/12/2017[Cigarette smoking (CS) is associated with vascular endothelial dysfunction in a causative way primarily related to the TS content of reactive oxygen species (ROS), nicotine, and inflammation. TS promotes glucose intolerance and increases the risk of developing type-2 diabetes mellitus (2DM) with which it shares other pathogenic traits including the high risk of cerebrovascular and neurological disorders like stroke via ROS generation, inflammation, and blood-brain barrier (BBB) impairment. Herein we provide evidence of the role played by nuclear factor erythroid 2-related factor (Nrf2) in CS-induced cerebrobvascular/BBB impairments and how these cerebrovascular harmful effects can be circumvented by the use of metformin (MF; a widely prescribed, firstline anti-diabetic drug) treatment. Our data in fact revealed that MF activates counteractive mechanisms primarily associated with the Nrf2 pathway which drastically reduce CS toxicity at the cerebrovascular level. These include the suppression of tight junction (TJ) protein downregulation and loss of BBB integrity induced by CS, reduction of inflammation and oxidative stress, renormalization of the expression levels of the major BBB glucose transporter Glut-1 and that of the anticoagulant factor thrombomodulin. Further, we provide additional insights on the controversial interplay between Nrf2 and AMPK121098- field[33]: Not in FilevB?:Prieto-Barrios, M. Velasco-Tamariz, V. Tous-Romero, F. Burillo-Martinez, S. Zarco-Olivo, C. Rodriguez-Peralto, J.L. Ortiz-Romero, P.L.2017nLinear immunoglobulin A dermatosis mimicking toxic epidermal necrolysis: a case report of etanercept treatmentBritish Journal of Dermatology$online early: doi: 10.1111/bjd.15400not published, 01 Mar 17agent case CASE REPORT Case-report CLINICAL CUTANEOUS DERMAL DIAGNOSIS dose drug-induced eruption ETANERCEPT HISTOPATHOLOGY HOSPITAL IS LESIONS MORTALITY NECROSIS SINGLE-DOSE THERAPEUTIC toxic TREATMENT US use VANCOMYCIN 2/21/2017A 65-year-old pluripathological woman attended our hospital with a cutaneous eruption of sudden appearance after vancomycin treatment. She presented targetoid lesions affecting approximately 25-30% of her body surface, large erosions, with mucosal lesions and positive Nikolsky sign. Under the initial clinical suspicion of Toxic Epidermal Necrolysis (TEN), and considering recent literature of its successful use in these cases, she was treated with a single dose of anti-Tumor Necrosis Factor (anti-TNF) agent etanercept. Subsequently, the exanthema progression stopped and resolution of the lesions happened in a few days. Later on, histopathology revealed a subepidermal blister with dense neutrophilic infiltrate and linear deposits of IgA on the dermoepidermal junction allowing us to stablish the diagnosis of drug-induced linear immunoglobulin A (IgA) dermatosis mimicking TEN. Linear IgA dermatosis can have severe clinical manifestations, even mimicking TEN, with high mortality, especially the drug-induced cases. We have not found any other report of linear IgA dermatosis treated with etanercept in the English literature. Anti-TNF medications could represent useful therapeutic alternatives in this dermatosis. This article is protected by copyright. All rights reserved120953# field[33]: Not in File ?;Qiu, T.A. Nguyen, T.H. Hudson-Smith, N.V. Clement, P.L. Forester, D.-C. Frew, H. Hang, M.N. Murphy, C.J. Hamers, R.J. Feng, Z.V. Haynes, C.L.2017tGrowth-based bacterial viability assay for interference-free and high-throughput toxicity screening of nanomaterials 2057-2064Analytical Chemistry893 ACID agent analysis ANALYTICAL As ASSAY ASSESSMENT BACTERIA CELL chemical COMPUTER DATA EXPOSURE GROWTH high throughput impact IS method Nanomaterials NANOPARTICLES Polymerase Chain Reaction r REACTIONS RESIDUE RISK RISK ASSESSMENT SCREENING Toxicities TOXICITY use2/7/2017^Current high-throughput approaches evaluating toxicity of chemical agents toward bacteria typically rely on optical assays, such as luminescence and absorbance, to probe the viability of the bacteria. However, when applied to toxicity induced by nanomaterials, scattering and absorbance from the nanomaterials act as interferences that complicate quantitative analysis. Herein, we describe a bacterial viability assay that is free of optical interference from nanomaterials and can be performed in a high-throughput format on 96-well plates. In this assay, bacteria were exposed to various materials and then diluted by a large factor into fresh growth medium. The large dilution ensured minimal optical interference from the nanomaterial when reading optical density, and the residue left from the exposure mixture after dilution was confirmed not to impact the bacterial growth profile. The fractions of viable cells after exposure were allowed to grow in fresh medium to generate measurable growth curves. Bacterial viability was then quantitatively correlated to the delay of bacterial growth compared to a reference regarded as 100% viable cells; data analysis was inspired by that in quantitative polymerase chain reactions, where the delay in the amplification curve is correlated to the starting amount of the template nucleic acid. Fast and robust data analysis was achieved by developing computer algorithms carried out using R. This method was tested on four bacterial strains, including both Gram-negative and Gram-positive bacteria, showing great potential for application to all culturable bacterial strains. With the increasing diversity of engineered nanomaterials being considered for large-scale use, this high-throughput screening method will facilitate rapid screening of nanomaterial toxicity and thus inform the risk assessment of nanoparticles in a timely fashion120942/ field[33]: Not in File f?<F?Querobino, S.M. Carrettiero, D.C. Costa, M.S. Alberto-Silva, C.2017Neuroprotective property of low molecular weight fraction from B. jararaca snake venom in H2O2-induced cytotoxicity in cultured hippocampal cells134-143Toxicon129Sanalysis apoptosis As ASSAY BOTHROPS CELL central nervous system CONCENTRATIONS CYTOCHROME CYTOTOXICITY Development DISEASE DRUG drugs HYDROGEN HYDROGEN PEROXIDE IDENTIFICATION MEMBRANE MTT Assay Neuroprotection OXIDATIVE STRESS Peroxide PROTEIN proteins SNAKE VENOM STRESS STUDY SUPEROXIDE SUPEROXIDE DISMUTASE Time TREATMENT Venom WEIGHT 2/16/2017In central nervous system cells, low molecular weight fractions (LMWF) from snake venoms can inhibit changes in mitochondrial membrane permeability, preventing the diffusion of cytochrome c to the cytoplasm, inhibiting the activation of pro-apoptotic factors. Here, we evaluated the neuroprotective activity of LMWF from Bothrops jararaca (Bj) snake venom in H2O2-induced cytotoxicity in cultured hippocampal cells. SDS-PAGE, FT-IR and MALDI-TOF analysis of LMWF (<14 kDa) confirmed the absence of high-molecular-weight proteins in the fraction. LMWF did not present cytotoxicity in all concentrations and time tested by MTT assay. Neuroprotection was evaluated in cells pretreated with LMWF for 4 h prior to the addition of 50 muM H2O2 for 20 h. We demonstrated that LMWF reduced the argininosuccinate synthase (AsS) and superoxide dismutase (SOD1) expressions, suggesting that this fraction as an effective neuroprotective compound that could increase the hippocampal cells viability by attenuation of oxidative stress. In addition, LMWF protects against apoptosis induced by H2O2, reducing the expression of caspase-3 and caspase-8. Overall, this study opens new perspectives for the identification of new molecules for the development of drugs applied to the treatment of neurodegenerative diseases121134/ field[33]: Not in FileB?=BQuerques, L. Miserocchi, E. Modorati, G. Querques, G. Bandello, F.2017lHemorrhagic occlusive retinal vasculitis after inadvertent intraocular perforation with gentamycin injection!European Journal of Ophthalmology&online early: doi: 10.5301/ejo.5000874not published, 01 Mar 17ANGIOGRAPHY As CAPILLARY case CHRONIC CLINICAL DIAGNOSIS dose edema errors EYE hemorrhage INJECTION INTRAOCULAR KERATITIS method methods OCULAR pain TOMOGRAPHY Toxicities TOXICITY VASCULAR Vasculitis Visual Acuity 2/22/2017PURPOSE: To report a case of hemorrhagic occlusive retinal vasculitis (HORV) secondary to intraocular toxicity due to inadvertent intraocular injection of gentamycin. METHODS: A 21-year-old woman was referred to our department because of severe ocular pain and sudden visual loss in her left eye after she received a subconjunctival gentamycin injection for chronic infectious keratitis. RESULTS: At presentation, best-corrected visual acuity was 20/20 in the right eye and counting fingers in the left eye. Fundus examination showed diffuse intraretinal and perivascular hemorrhages, vascular cuffing, white-centered hemorrhages, and diffuse retinal edema. Fluorescein angiography confirmed occlusive retinal vasculitis with capillary nonperfusion and spectral-domain optical coherence tomography revealed ischemic macular edema. The clinical diagnosis was compatible with HORV secondary to retinal toxicity due to high dose of intraocular gentamycin. CONCLUSIONS: We report a case of HORV secondary to inadvertent subconjunctival gentamycin injection. Ocular perforation and high dose of intravitreal gentamycin administration should be considered as a potential cause of HORV following subconjunctival injection121000% field[33]: Not in File "?>Quintero, G.C.2017PReview about gabapentin misuse, interactions, contraindications and side effects13-21$Journal of Experimental Pharmacology9ABUSE ACID ANIMAL ANTICONVULSANT Antiepileptic As CAFFEINE case case studies Case Study CLINICAL clinical studies Clinical study dose DRUG drugs FAILURE fatalities fatality GABAPENTIN HYPOVENTILATION INTERACTION IS LOSARTAN MAGNESIUM MAGNESIUM OXIDE MEFLOQUINE METHADONE MISUSE MORPHINE MYASTHENIA GRAVIS MYOCLONUS MYOPATHY OPIOID Opioid withdrawal PHENYTOIN PUBLICATION RESPIRATORY RESPIRATORY FAILURE REVIEW RISK Side effect side effects side-effects STUDY SUBSTANCE ABUSE SYMPTOMS TERATOGENICITY use WITHDRAWAL Withdrawal symptoms2017The current work is targeted to review the risks of gabapentin misuse, its potential interactions with other drugs, side effects and use contraindications. This review consists of a total of 99 biographical references (from the year 1983 to 2016). A publication search of PubMed was performed from January 1983 to December 2016. It included animal studies, clinical studies, case studies and reviews related to gabapentin misuse, potential interactions, side effects and use contraindications. The search terms were gabapentin, anticonvulsant and antiepileptic. In general, it seems that gabapentin has risks of being misused based on the increased level of prescriptions, related fatalities, recreational misuse and higher doses of self-administration. The main reasons for gabapentin misuse are as follows: getting high, alleviating opioid withdrawal symptoms and potentiating methadone effects. Some of the main substances that interact with gabapentin are morphine, caffeine, losartan, ethacrynic acid, phenytoin, mefloquine and magnesium oxide. Some of the side effects caused by gabapentin are teratogenicity, hypoventilation, respiratory failure and myopathy. Finally, reports in general contraindicate the use of gabapentin in conditions such as myasthenia gravis and myoclonus121044# field[33]: Not in FileC??*Radenkova-Saeva, J. Loukova, A. Tsekov, C.20166Caustic injury in adults – A study for 3 year period39-44Acta Medica Bulgarica4320ACUTE ADULT Age agent ALKALINE As CAUSTIC caustic injuries CLINICAL complications CORROSIVES FEMALE HOSPITAL Imaging INGESTION injuries Injury IS Laboratories LABORATORY MALE method methods Motivation Observation PATHOLOGY PATIENT POISONING poisonings PSYCHIATRIC SEVERITY STRICTURE STUDY TEST TOXICOLOGY20165The aim of the study is to present the results of a 3-year clinico-epidemiological investigation of caustic injury in adults. The study includes 43 patients with acute corrosive ingestion, hospitalized in the Toxicology Clinic, University Hospital "N. I. Pirogov", Sofia, Bulgaria, for the period 01.01. 2010-31.12.2012. The methods used include: clinical observation and examination, clinical laboratory, imaging, and psychiatric methods and tests. 43 patients between the ages of 22 and 82 with acute corrosive ingestions have been observed. Eleven were male (25.6%) and 32 female (74.4%). All ingestions were intentional. Alkaline agents were used by all of the patients. The severity of poisonings varied from moderate to extremely severe. Different complications were seen in 82% of the cases-severe bleeding, perforation, fistula or/and stricture formation. Two of the patients have undergone surgical intervention-coloesophagoplastic-and have recovered completely. The motivation in different age groups was also studied. Psychiatric comorbidity occurred in patients as depressive and schizoaffective disorder, as well as existential crises. Acute corrosive ingestions by alkaline agents cause severe pathology. The severity and complex character of the injuries require good coordination between different medical specialists120686' field[33]: Not in FileB?@Ragot, C. Gerbaud, E. Boyer, A.2017?Terlipressin in refractory shock induced by diltiazem poisoning&American Journal of Emergency Medicine-online early: doi: 10.1016/j.ajem.2017.01.062#not published, 16 Feb 17, 17 Mar 17ACIDOSIS CALCIUM CHANNELS DEATH DILTIAZEM dose EPINEPHRINE FAILURE LACTATE MULTIPLE ORGAN FAILURE NOREPINEPHRINE PATIENT POISONING SHOCK STATUS TERLIPRESSIN THERAPY 1/27/2017Poisoning caused by calcium-channels blockers (CCB) can cause refractory vasoplegic shock, resulting in multiple-organ failure and death despite maximal therapy including high doses of vasopressors. We report one CCB-induced refractory shock complicated with lactate acidosis despite very high doses of epinephrine and norepinephrine. The hemodynamic status of the patient dramatically improved after intermittent boluses of terlipressin, which corrected the acidosis120692, field[33]: Not in FileB?A Raistrick, D.2017>Are UK opioid substitution treatment agencies fit for purpose? Addiction$online early: doi: 10.1111/add.13737not published, 16 feb 17/maintenance OPIOID Opioids THERAPY TREATMENT UK2/2/2017120688# field[33]: Not in File?BNRaleigh, K.K. Alexander, B.H. Ramachandran, G. Morey, S.Z. Logan, P. Olsen, G.2012~Occupational exposure to ammonium perfluorooctanoate: exploring two exposure models to account for workers' exposure over time617-618Reproductive Toxicology334ABSTRACT ACID ADULT AIR AIR CONCENTRATION AMMONIA As Body burden burden CONCENTRATIONS DATA dose duration ELIMINATION EMPLOYMENT EPIDEMIOLOGY EXPOSURE Exposure estimates Exposure reconstruction FACILITIES Frequency HEALTH Health effects HUMAN Human health method methods MODEL MONITORING OCCUPATIONAL occupational epidemiology OCCUPATIONAL EXPOSURE outcome PERFLUOROOCTANOATE perfluorooctanoic acid PFOA ranking RESEARCH STUDY Time US WHO workers20121208350 field[33]: Not in File ^B?CURatnayake, I. Shihana, F. Dissanayake, D.M. Buckley, N.A. Maduwage, K. Isbister, G.K.2017Performance of the 20-minute whole blood clotting test in detecting venom induced consumption coagulopathy from Russell's viper (Daboia russelii) bitesThrombosis and Haemostasis'online early: doi: 10.1160/TH16-10-0769not published, 21 Feb 17ADULT ANTIVENOM As BLOOD case CLINICAL COAGULATION COAGULOPATHY Consumption DETECTION DIAGNOSIS envenoming glass HOSPITAL INR IS NO PATIENT PROTHROMBIN TIME RESEARCH Russell's viper Sensitivity snake bite TEST Time Venom VIPER2/2/2017The 20-minute whole blood clotting test (WBCT20) is used as a bedside diagnostic test for coagulopathic snake envenoming. We aimed to assess the performance of the WBCT20 in diagnosis of venom induced consumption coagulopathy (VICC) in Russell's viper envenoming. Adult patients admitted with suspected snake bites were recruited from two hospitals. WBCT20 and prothrombin time (PT) test were performed on admission. WBCT20 was done by trained clinical research assistants using 1 ml whole blood in a 5 ml borosilicate glass tube with a 10 mm internal diameter. The PT was measured by a semi-automated coagulation system and international normalised ratio (INR) calculated. VICC was defined as present if the INR was >1.4. The diagnostic utility of WBCT20 was determined by calculating the sensitivity and specificity of the WBCT20 on admission for detecting VICC. There were 987 snake bites where both WBCT20 and PT were done on admission samples. This included 79 patients (8 %) with VICC. The WBCT20 was positive in 65/79 patients with VICC (sensitivity 82 %; 95 % confidence interval [CI]: 72-90 %) and was falsely positive in 13/908 with no coagulopathy. The WBCT20 was negative in 895/908 snake bites with no coagulopathy (specificity: 98 % 95 % CI: 97-99 %) and was falsely negative in 14/79 with VICC. Using trained clinical staff, the WBCT20 test had a relatively good sensitivity for the detection of VICC, but still missed almost one fifth of cases where antivenom was potentially indicated120813& field[33]: Not in FileA?DRaval, A.N. Cigarroa, J.E. Chung, M.K. Diaz-Sandoval, L.J. Diercks, D. Piccini, J.P. Jung, H.S. Washam, J.B. Welch, B.G. Zazulia, A.R. Collins, S.P.2017Management of patients on non-vitamin K antagonist oral anticoagulants in the acute care and periprocedural setting: a scientific statement from the American Heart Association e604-e633 Circulation135<ACUTE ANTAGONIST ANTICOAGULANT anticoagulants ANTIDOTE As ASSAY Association ATRIAL FIBRILLATION CLINICAL dabigatran DATA HEART Idarucizumab INGESTION IS Knowledge Laboratories LABORATORY MANAGEMENT Measurement NO ORAL PATIENT PREVENTION PROTOCOL RENAL RENAL FUNCTION RISK STROKE Time TRIAL UNITED STATES WARFARIN WHO2/6/2017MNon-vitamin K oral anticoagulants (NOACs) are now widely used as alternatives to warfarin for stroke prevention in atrial fibrillation and management of venous thromboembolism. In clinical practice, there is still widespread uncertainty on how to manage patients on NOACs who bleed or who are at risk for bleeding. Clinical trial data related to NOAC reversal for bleeding and perioperative management are sparse, and recommendations are largely derived from expert opinion. Knowledge of time of last ingestion of the NOAC and renal function is critical to managing these patients given that laboratory measurement is challenging because of the lack of commercially available assays in the United States. Idarucizumab is available as an antidote to rapidly reverse the effects of dabigatran. At present, there is no specific antidote available in the United States for the oral factor Xa inhibitors. Prothrombin concentrate may be considered in life-threatening bleeding. Healthcare institutions should adopt a NOAC reversal and perioperative management protocol developed with multidisciplinary input120864.[RefMgr field[33]: Not in File EB?EKRavelli, K.G. Ramos, A.d.T. Gonçalves, L.B. Magnoli, F.C. Troncone, L.R.P.2017dPhoneutria nigriventer spider toxin Tx2-6 induces priapism in mice even after cavernosal denervationToxicon0online early: doi: 10.1016/j.toxicon.2017.02.026not published, 01 Mar 17ANIMAL Animals As ASSESSMENT DEATH FAILURE FIBROSIS HUMAN Humans IN VIVO Inhibition MECHANISM MICE NERVE PHONEUTRIA RESPIRATORY RESPIRATORY FAILURE SODIUM SODIUM CHANNEL SPIDER STUDY TISSUE toxin TOXINS VASCULAR 2/24/2017The Phoneutria nigriventer spider toxin Tx2-6 causes priapism in humans and mice. This toxin produces a delay in Sodium channel inactivation, generalized vascular congestion and death by respiratory failure. NO-Synthase inhibitors seem to abolish toxin-induced priapism. The understanding of the ultimate molecular mechanism involved in toxin-induced priapism may shed light on aspects of erectile function/dysfunction. This study investigates if cavernosal denervation can abolish the toxin-induced priapism. Surgical cavernosal nerve excision/denervation was performed in mice and confirmed by infertility, histological assessment of fibrosis and immunohistochemical staining for synaptophysin. Denervated mice showed intense fibrosis of the cavernosal tissue as well as absence of synaptophysin IHC staining; surprisingly mice showed toxin-induced priapism when tested 15, 30 or 60 days after denervation. While sham-operated mice presented full priapism, denervated animals showed only partial priapism possibly due to the fibrosis. These results reveal that erection caused by Tx2-6 toxin may not depend on cavernosal nerves integrity. The effect of this toxin on sodium channels seem not directly involved in priapism as many toxins have identical effects but do not induce priapism. Discussion approaches the many different potential sites of intervention listed in the signaling cascades of NO/cGMP, RhoA/Rho-Kinase, as well as the emerging new gasotransmitter H2S. The pharmacological inhibition of Rho-kinase and toxin Tx2-6 have similar effects in vivo121137/ field[33]: Not in File ?FeRawat, A. Dubey, D. Guleria, A. Kumar, U. Keshari, A.K. Chaturvedi, S. Prakash, A. Saha, S. Kumar, D.2016a1H NMR-based serum metabolomics reveals erythromycin-induced liver toxicity in albino Wistar rats327-334*Journal of Pharmacy and Bioallied Sciences84ACID agent ALANINE AMINO ACID analysis CITRATE DIMETHYLAMINE DISEASE drug-induced EFFICACY ERYTHROMYCIN EXPERIMENTAL GLUCOSE glutamate glutamine GLYCEROL HEPATIC HEPATOTOXICITY IS LACTATE LEVELS LIPID LIVER LIVER DISEASE MAGNETIC RESONANCE MALE Male rat MECHANISM METABOLISM metabolomics MODEL NMR Oxidation OXIDATIVE STRESS RAT rats SERUM STRESS STUDY toxic TOXIC RESPONSE Toxicities TOXICITY Wistar rat Wistar rats10/2016INTRODUCTION: Erythromycin (ERY) is known to induce hepatic toxicity which mimics other liver diseases. Thus, ERY is often used to produce experimental models of drug-induced liver-toxicity. The serum metabolic profiles can be used to evaluate the liver-toxicity and to further improve the understanding of underlying mechanism. OBJECTIVE: To establish the serum metabolic patterns of Erythromycin induced hepatotoxicity in albino wistar rats using 1H NMR based serum metabolomics. EXPERIMENTAL: Fourteen male rats were randomly divided into two groups (n = 7 in each group): control and ERY treated. After 28 days of intervention, the metabolic profiles of sera obtained from ERY and control groups were analyzed using high-resolution 1D 1H CPMG and diffusion-edited nuclear magnetic resonance (NMR) spectra. The histopathological and SEM examinations were employed to evaluate the liver toxicity in ERY treated group. RESULTS: The serum metabolic profiles of control and ERY treated rats were compared using multivariate statistical analysis and the metabolic patterns specific to ERY-induced liver toxicity were established. The toxic response of ERY was characterized with: (a) increased serum levels of Glucose, glutamine, dimethylamine, malonate, choline, phosphocholine and phospholipids and (b) decreased levels of isoleucine, leucine, valine, alanine, glutamate, citrate, glycerol, lactate, threonine, circulating lipoproteins, N-acetyl glycoproteins, and poly-unsaturated lipids. These metabolic alterations were found to be associated with (a) decreased TCA cycle activity and enhanced fatty acid oxidation, (b) dysfunction of lipid and amino acid metabolism and (c) oxidative stress. CONCLUSION AND RECOMMENDATIONS: Erythromycin is often used to produce experimental models of liver toxicity; therefore, the established NMR-based metabolic patterns will form the basis for future studies aiming to evaluate the efficacy of anti-hepatotoxic agents or the hepatotoxicity of new drug-formulations121058- field[33]: Not in FileB?GReddy, D.S. Colman, E.2017gA comparative toxidrome analysis of human organophosphate and nerve agent poisonings using social media"Clinical and Translational Science$online early: doi: 10.1111/cts.12435not published, 01 Mar 17Age agent analysis ANTIDOTE Antidotes As chemical CHOLINERGIC COMPARATIVE Convulsion CONVULSIONS DATA DATABASE DETECTION EXPOSURE FOLLOW UP Follow-up GAP Gender HUMAN IDENTIFICATION lethal Long term Long-term NERVE NERVE AGENT nerve agent poisoning nerve agents op organophosphate Organophosphates POISONING poisonings SEVERITY SOCIAL Social media Source SYMPTOMS Toxicities TOXICITY 2/26/2017yHere we utilized social media to compare the toxidrome of three lethal chemical exposures worldwide. YouTube videos were the main source from which the data were collected, but published reports and news were also utilized to fill in some gaps. All videos were organized in a database detailing symptoms and severity of each victim, along with demographics such as approximate age and gender. Each symptom was rated as mild, moderate, or severe and corresponding pie graphs for each incident were compared. The videos displayed symptoms ranging from mild to severe cholinergic toxicity and life-threatening convulsions. Social media may represent an important resource in developing a viable approach to the early detection and identification of chemical exposure, reinforce our preparedness for better antidotes, long-term follow up, and training about deadly chemical nerve agent attacks120970# field[33]: Not in FilezB?H$Reed, B.A. Sabourin, C.L. Lenz, D.E.2017AHuman butyrylcholinesterase efficacy against nerve agent exposure/Journal of Biochemical and Molecular Toxicology$online early: doi: 10.1002/jbt.21886not published, 01 Mar 17[ACETYLCHOLINESTERASE agent ANIMAL animal models ANTIDOTE As BRAIN Brain damage BUTYRYLCHOLINESTERASE CHOLINERGIC Cholinergic crisis DEATH EFFICACY EXPOSURE FDA HEALTH HUMAN IS Long term Long-term MILITARY MODEL NERVE NERVE AGENT nerve agent poisoning nerve agents op organophosphorus POISONING PRETREATMENT seizure SEIZURES STUDY THERAPY USAGE use 2/22/2017Acetylcholinesterase is vital for normal operation of many processes in the body. Following exposure to organophosphorus (OP) nerve agents, death can ensue without immediate medical intervention. Current therapies mitigate the cholinergic crisis caused by nerve agents but do not fully prevent long-term health concerns, for example, brain damage following seizures. Human butyrylcholinesterase (HuBChE) is a stoichiometric bioscavenger being investigated as an antidote for OP nerve agent poisoning. HuBChE sequesters OP nerve agent in the bloodstream preventing the nerve agent from reaching critical target organ systems. HuBChE was effective when used as both a pre-treatment and as a post-exposure therapy. HuBChE has potential for use in both military settings and to protect civilian first responders in situations where nerve agent usage is suspected. We reviewed various animal models studies evaluating the efficacy of HuBChE against nerve agent exposure, pursuant to its submission for approval under the FDA Animal Rule121040# field[33]: Not in File B?I>Regolisti, G. Antoniotti, R. Fani, F. Greco, P. Fiaccadori, E.2017Treatment of metformin intoxication complicated by lactic acidosis and acute kidney injury: the role of prolonged intermittent hemodialysis#American Journal of Kidney Diseases-online early: doi: 10.1053/j.ajkd.2016.12.010not published, 01 Mar 17ACIDOSIS ACUTE Acute kidney injury ANION GAP As case CHRONIC chronic kidney disease CLEARANCE CLINICAL CONCENTRATIONS Confirmation CREATININE DIAGNOSIS DIALYSIS DISEASE dose DRUG drug clearance GAP HAEMODIALYSIS hemodialysis injuries Injury INTOXICATION IS KIDNEY kidney injury Laboratories LABORATORY LACTIC ACIDOSIS lethal Liquid chromatography tandem mass spectrometry Liquid chromatography-tandem mass spectrometry MASS SPECTROMETRY Measurement METABOLIC ACIDOSIS METFORMIN NEPHROTOXICITY PATHOPHYSIOLOGY PATIENT pharmacokinetic Redistribution RENAL Renal replacement therapy SERUM SPECTROMETRY Sustained low-efficiency dialysis SYMPTOMS TECHNIQUE THERAPY TREATMENT 2/17/2017Metformin intoxication with lactic acidosis, a potentially lethal condition, may develop in diabetic patients when the drug dose is inappropriate and/or its clearance is reduced. Diagnosis and therapy may be delayed due to nonspecific symptoms at presentation, with severe anion gap metabolic acidosis and elevated serum creatinine values being the most prominent laboratory findings. Confirmation requires measurement of serum metformin by high-performance liquid chromatography-tandem mass spectrometry, but this technique is available only at specialized institutions and cannot be relied on as a guide to immediate treatment. Thus, based on strong clinical suspicion, renal replacement therapy must be started promptly to achieve efficient drug clearance and correct the metabolic acidosis. However, because metformin accumulates in the intracellular compartment with prolonged treatment, a rebound in serum concentrations due to redistribution is expected at the end of dialysis. We report a case of metformin intoxication, severe lactic acidosis, and acute kidney injury in a diabetic patient with pre-existing chronic kidney disease stage 3, treated effectively with sustained low-efficiency dialysis. We discuss the pathophysiology, differential diagnosis, and treatment options and highlight specific pharmacokinetic issues that should be considered in selecting the appropriate modality of renal replacement therapy120937, field[33]: Not in FileLB?J#Rencher, L. Schwartz, J. Wilson, A.2016LAn anaphylactoid reaction to rattlesnake envenomation in a pediatric patientPediatric Emergency Care/online early: doi: 10.1097/PEC.0000000000000977not published, 21 Feb 17ABSTRACT AIRWAY case Development ENVENOMATION EXPOSURE history IS NO PAEDIATRIC PATIENT pediatric RATTLESNAKE SENSITIZATION snake bite SNAKE VENOM Snakes SYMPTOMS Venom WHO2016TABSTRACT: Rattlesnake envenomation causes a spectrum of symptoms and signs, many of which closely resemble an anaphylactic reaction. Development of airway compromise after a snake bite to an extremity is unusual, but has been previously reported. The majority of such reports detail a history of probable sensitization from previous contact with snakes or snake venom. Few reports exist without such previous contact; no reports are of pediatric cases. Here we present a 14-year-old boy with no history of prior snake exposure who presents with an anaphylactoid reaction after a rattlesnake bite.120803. field[33]: Not in File B?KEReshi, M.S. Shrivastava, S. Jaswal, A. Sinha, N. Uthra, C. Shukla, S.2017OGold nanoparticles ameliorate acetaminophen induced hepato-renal injury in rats&Experimental and Toxicologic Pathology,online early: doi: 10.1016/j.etp.2017.01.009not published,20 Feb 17ACETAMINOPHEN ALBUMIN ANIMAL Animals As Bilirubin CATALASE CHOLESTEROL CLINICAL clinical studies Clinical study Complementary medicine CREATININE Development DISEASE dose DRUG EFFICACY EXPOSURE GOLD GSH HEPATIC HEPATOTOXICITY injuries Injury INTOXICATION IS KIDNEY LIVER Medicine NANOPARTICLES NEPHROTOXICITY OXIDATIVE STRESS PARACETAMOL RAT rats RENAL RENAL DISEASE SERUM SILYMARIN STRESS STUDY THERAPEUTIC Toxicities TOXICITY TREATMENT UREA 1/30/2017Valuable effects of gold particles have been reported and used in complementary medicine for decades. The aim of this study was to evaluate the therapeutic efficacy of gold nanoparticles (AuNPs) against acetaminophen (APAP) induced toxicity. Albino rats were administered APAP at a dose of 2g/kg p.o. once only. After 24h of APAP intoxication, animals were treated with three different doses of AuNPs (50mug/kg, 100mug/kg, 150mug/kg) orally or silymarin at a dose of 50mg/kg p.o., once only. Animals of all the groups were sacrificed after 24h of last treatment. APAP administered group showed a significant rise in the AST, ALT, SALP, LDH, cholesterol, bilirubin, albumin, urea and creatinine in serum which indicated the hepato-renal damage. A significantly enhanced LPO and a depleted level of GSH were observed in APAP intoxicated rats. Declined activities of SOD and Catalase, after acetaminophen exposure indicated oxidative stress in liver and kidney. The activities of ATPase and glucose-6-Phosphatase were significantly inhibited after APAP administration. AuNPs treatment reversed all variables significantly towards normal level and was found nontoxic. Thus it is concluded that gold nanoparticles played a beneficial role in reducing acetaminophen induced toxicity and can be used in the development of drug against hepatic as well as renal diseases, after further preclinical and clinical studies120766+ field[33]: Not in File ?L!Rey, V. Botana, A.M. Botana, L.M.2017Quantification of PSP toxins in toxic shellfish matrices using post-column oxidation liquid chromatography and pre-column oxidation liquid chromatography methods suggests post-column oxidation liquid chromatography as a good monitoring method of choice28-35Toxicon129ANALYTICAL As CHROMATOGRAPHY COMPARISON DATA INFORMATION IS Liquid chromatography method methods MONITORING Oxidation POISONING quantification SHELLFISH t TEST Time toxic toxin TOXINS use 2/13/2017Different shellfish samples were analyzed by Pre- and Post-Column Oxidation Liquid Chromatography to compare the toxins profiles and get information about the degree of accomplishment of both methods. Comparison of the results obtained, the linear correlation coefficient (r2 = 0.94) and the paired t test (two tails, alpha = 0.05), indicated that there were not significant differences between both sets of data. Nevertheless, important differences related to toxins profiles were found: it was remarkable the difference in results for both Gonyautoxins 1 and 4 and Decarbamoylgonyautoxins 2 and 3, depending on the method of choice, due to an overestimation in the Pre-Column method. It was necessary to modify the elution conditions in the Post-Column method to avoid the interference of matrix peaks at retention times closer to the retention times of the calibrants, mostly when working with oyster and scallop matrices, although it is a good method to use routinely121139/ field[33]: Not in File lB?MRoca Comas, A. Vila Domenech, J.S. Massa Solé, J. Timoneda Paz, P. Peñas Boira, M. Herrero Espinet, F.J. Sánchez Jiménez, J. Ballester Martínez, A.2017dPrevalence of illicit drug use at the end of pregnancy: a cross-sectional study at the time of birthMinerva Pediatrica1online early: doi: 10.23736/S0026-4946.17.04664-3not published, 28 Feb 18hABORTION ABUSE Adverse analysis CANNABIS Consumption DRUG DRUG ABUSE Drug use drugs Drugs of abuse history HOSPITAL Illicit drug Illicit drug use IS method methods Multivariate analysis NO OPIOID Opioids outcome PAEDIATRIC PERINATAL Population PREGNANCY PREMATURE prevalence QUESTIONNAIRE Spain STUDY SUBSTANCE ABUSE TEST Testing Time toxic URINE use WHO WOMEN2/7/20177BACKGROUND: Drug use during pregnancy is associated with adverse perinatal outcomes. This study was conducted to assess the prevalence of consumption of drugs of abuse in pregnant women at the end of gestation. METHODS: Cross-sectional study of all consecutive pregnant women in labor admitted to a regional hospital in Calella (Barcelona, Spain) in labor over one year period (2014- 2015). Women who gave written consent to take part in the study provided a urine sample on admission and completed a questionnaire with toxic habits-related questions. RESULTS: The study population included 862 women, 721 (83.6%) of which agreed to participate. Of the 721 urine samples obtained, 719 (99.7%) were valid for analysis. The prevalence of drugs of abuse was 5.4% (n = 39). Cannabis was the most frequently detected substance. No participant tested positive for opioids. In the multivariate analysis, predictors of illicit drug use were history of more than two abortions, premature delivery, self-reporting of consumption during pregnancy, poor obstetric control during gestation, and consideration of vulnerable pregnant woman. Based on the ß coefficients of these five factors, a scoring system for discriminating positivity or negativity of drugs of abuse in urine testing was calculated (area under the ROC curve 0.84). CONCLUSIONS: The prevalence of consumption of drugs of abuse at the end of pregnancy was 5.4%. A simple test based on five anamnestic variables is useful to discriminate women with positive and negative results of urine testing for drugs of abuse tested in this study.1209060 field[33]: Not in File B?NORodda, L.N. Pilgrim, J.L. Di Rago, M. Crump, K. Gerostamoulos, D. Drummer, O.H.2017IA cluster of fentanyl-laced heroin deaths in 2015 in Melbourne, Australia Journal of Analytical Toxicology online early: 10.1093/jat/bkx013not published, 20 Feb 1796-acetylmorphine Age analysis Australia BLOOD blood concentration case cluster DEATH Deaths DRUG drugs fatalities fatality FEMALE FENTANYL HEALTH HEROIN IS Laboratories LABORATORY LC-MS-MS MALE MORPHINE NO OPIOID prevalence PREVENTION PUBLIC PUBLIC HEALTH STUDY THERAPEUTIC TOXICOLOGY URINE Urine analysis use WHO2/3/2017qThe prevalence of opioid use in therapeutic and recreational settings has steadily increased throughout the western world. The addition of fentanyl into heroin products can produce potentially dangerous consequences, even to opioid tolerant individuals who may be unaware of such additions. Following an observed spike of heroin-fentanyl related deaths in Melbourne, Australia, a study was undertaken to determine the prevalence of these cases. All reportable deaths occurring in Victoria during 2015 and submitted to the toxicology laboratory were analysed using LC-MS-MS to confirm the combination of the heroin marker 6-acetylmorphine and/or morphine, and fentanyl. Over 4,000 coronial cases in 2015 underwent toxicological analysis for these drugs, there were nine cases identified that involved fentanyl-laced heroin. There was no specific mention of fentanyl use in any of these cases. All occurred within 2 months and in two distinct locations. The first four deaths occurred within 3 days of each other, in neighboring suburbs. The ages ranged from 25 to 57 years with an average of 40 and median of 37 years, and consisted of eight males and one female. The average and median femoral blood concentration of fentanyl was 18 and 20 ng/mL (range: <1-45 ng/mL), and morphine 140 and 80 ng/mL (range: 20-400 ng/mL), respectively. All nine cases had 6-acetylmorphine detectable in blood. Urine analysis was also performed where available. A syringe, powder and spoon found at the scene of one case were also analysed and found to be positive for both heroin and fentanyl, which supported the likelihood of fentanyl-laced heroin. This is the first reported case series of fatalities involving heroin and fentanyl outside of North America in published literature. These findings may help inform public health and prevention strategies serving to decrease the potential for such fatalities in the future.120772$ field[33]: Not in File B?ORolland, B. Bouhassira, D. Authier, N. Auriacombe, M. Martinez, V. Polomeni, P. Brousse, G. Schwan, R. Lack, P. Bachellier, J. Rostaing, S. Bendimerad, P. Vergne-Salle, P. Dematteis, M. Perrot, S.2017bMésusage et dépendance aux opioïdes de prescription : prévention, repérage et prise en chargeRevue de Medecine Interne/online early: doi: 10.1016/j.revmed.2016.12.024not published, 01 Mar 17ABUSE ADDICTION Age BUPRENORPHINE complications dependence Depressive Disorder FATAL FOLLOW UP Follow-up history IDENTIFICATION IS LEAD Long term Long-term medication assisted treatment medication-assisted treatment METHADONE MISUSE MONITORING OPIOID Opioid withdrawal Opioids OVERDOSE pain PATIENT prescription opioids PREVENTION PSYCHIATRIC psychiatric disorder RISK SUBSTANCE ABUSE SYMPTOMS TOLERANCE TREATMENT use vulnerability WITHDRAWAL Withdrawal symptoms 2/14/2017Since the 1990s, the use of prescription opioids has largely spread, which has brought a real progress in the treatment of pain. The long-term use of prescription opioid is sometimes required, and may lead to pharmacological tolerance and withdrawal symptoms, i.e. pharmacological dependence on prescription opioids. Occasionally, this may also lead to misuse of prescription opioids (MPO). MPO preferentially occurs in vulnerable individuals, i.e., those with a young age, history of other addictive or psychiatric disorders, especially anxious and depressive disorders. MPO is associated with numerous complications, including an increased risk of fatal overdose. Prevention of MPO begins before the opioid prescription, with the identification of potential vulnerability factors. A planned and personalized monitoring should be systematically implemented. In vulnerable patients, contractualizing the prescription is warranted. During follow-up, the relevance of the prescription should be regularly reconsidered, according to the benefit observed on pain and the potential underlying signs of MPO. Patients with suspected MPO should be referred early to pain or addiction centers. The treatment of MPO should be based on multidisciplinary strategies, involving both the addiction and pain aspects: progressive opioid withdrawal, non-pharmacological measures against pain, or switching to medication-assisted treatment of addiction (i.e., buprenorphine or methadone)121182. field[22]: [Misuse and dependence on prescription opioids: prevention, identification and treatment]. In French with English abstract RefMgr field[33]: Not in File ?PkRoncero, C. Grau-López, L. Palma-Álvarez, R.F. Rodriguez-Cintas, L. Ros-Cucurull, E. Esojo, A. Daigre, C.2016ZHigher severity of cocaine addiction is associated with tactile and somatic hallucinations63-69European Psychiatry42ADDICTION Age analysis Association case CLINICAL COCAINE DATA DRUG Drug use HALLUCINATIONS INFORMATION IS method Multivariate analysis NO OVERDOSE PATIENT prevalence PSYCHIATRIC RISK SEVERITY STUDY SYMPTOMS Time TREATMENT use WHO 12/1/2016BACKGROUND: The aim of this study is to describe the features of cocaine-dependent patients who have had cocaine-induced tactile/somatic hallucinations (CITSH), and to analyze the association with addiction-related variables and psychiatric comorbidity, comparing patients with CITSH, patients with cocaine psychotic symptoms (CIP) and no CITSH, and patients without any psychotic symptom. METHOD: A cross-sectional study was conducted in 767 cocaine-dependent patients in an outpatient treatment center for addictions. The following data were obtained: sociodemographic characteristics, CIP information, addiction-related variables and psychiatric comorbidity. A bivariate and multivariate analysis was performed. RESULTS: Of the whole sample, 6.6% reported CITSH at some point of their lives, 48.4% had suffered some CIP other than CITSH, and 45% had not experienced any psychotic symptom. According to multivariate analysis, risk of overdose increases by 12.1 (OR) times the probability of having had CITSH compared patients with CIP-no-CITSH. Other variables associated to patients with CITSH were: age of drug use onset, presence of episodes of overdose, prevalence of psychotic disorder induced by cocaine. In general, in all variables studied, patients with CITSH presented worse clinical features (addiction variables and psychiatric comorbidity) than patients with CIP without CITSH and non-CIP group. CONCLUSION: CITSH are usually associated with other psychotic symptoms induced by cocaine. The patients who experienced CITSH are more severe cases compared both with patients with CIP without CITSH and patients without CIP. Increased risk of overdose is an important issue in this type of patients121004. field[33]: Not in File?QRoy, D.N. Goswami, R. Pal, A.2017MThe insect repellents: a silent environmental chemical toxicant to the health91-102)Environmental Toxicology and Pharmacology50UBenefits BIOACCUMULATION biological BIOTRANSFORMATION chemical CHEMICALS CLINICAL Environment ENVIRONMENTAL evidence hazardous HEALTH IN VITRO IN VIVO INFORMATION INSECT INSECT REPELLENT INTERACTION IS Knowledge METABOLITE Metabolites Pathway REVIEW Side effect side effects side-effects toxic TOXIC RESPONSE Toxicant Toxicities TOXICITY use 1/29/2017{In recent years, a large number of insect repellents have been developed with the idea of consumer benefits. In addition to already known advantageous application of insect repellents, there is increasing concern about the potential toxicity in environment leading to health caused by random use of these compounds. An increasing number of evidence suggests that insect repellents may trigger undesirable hazardous interactions with biological systems with a potential to generate harmful effects including intermediate metabolites. Biotransformation followed by bioaccumulation (vice e versa) may be an important phenomenon for toxic response of this chemicals. In this review, we have summarized the current state of knowledge on the insect repellent toxicity, including biochemical pathway alteration under in vitro and in vivo conditions considering different classes of organisms, from lower to higher vertebrate. Furthermore, we have tried to incorporate the effects of insect repellent in light of some clinical reports. We hope this review would provide useful information on potential side effects of uncontrolled use of insect repellents120880, field[33]: Not in FileB?R,Roy, M.P. Gupta, R. Bhatt, M. Aggarwal, K.C.2017BProfile of children hospitalized with acute poisoning in New DelhiIndian Pediatricsonline early: PMID:28159952not published, 20 Feb 17ACUTE acute poisoning Age case CHILDREN EPIDEMIOLOGY HOSPITAL INGESTION KEROSENE MALE Medicine medicines PAEDIATRIC POISONING Y2/2/20177195 cases of acute poisoning among children (age<12 y) in a tertiary hospital were identified over a period of one year. Two-thirds (63%) of them were males and 75% were below five years of age. Poisoning by medicines was most common (17%) followed by ingestion of corrosives/detergents (16%) and kerosene (14%)120770+ field[33]: Not in File ?S1Rozatkar, A.R. Kapoor, A. Sidana, A. Chavan, B.S.2016EClinical experience of baclofen in alcohol dependence: a chart review11-16Industrial Psychiatry Journal251Age agent ALCOHOL Alcohol consumption Alcohol dependence Alcohol use As ASSESSMENT BACLOFEN baseline cirrhosis CLINICAL Consumption craving dependence DOE dose DRUG EXPERIMENTAL experimental studies family history HOSPITAL India INDIUM INTOXICATION IS LIVER LIVER CIRRHOSIS MALE MANAGEMENT Motivation PATIENT Reduction REVIEW safe Side effect side effects side-effects STUDY Substance use SYMPTOMS TREATMENT TRIAL use WHO WITHDRAWAL Withdrawal symptoms1/2016INTRODUCTION: Craving is recognized as a formidable barrier in the management of patients with alcohol dependence. Among pharmacological agents that have been used in experimental studies for reduction in craving, baclofen appears to have a significant advantage over other agents. METHODOLOGY: The study is retrospective chart review of patients (n = 113) who have been treated with baclofen for alcohol dependence in a tertiary hospital of North India. Baseline assessments included sociodemography, motivation, quantity-frequency of alcohol use, and other alcohol-related clinical parameters. Weekly assessments, for a period of 4 weeks, were extracted from records which included dose of baclofen, craving intensity, and alcohol consumption. RESULTS: The study sample was predominantly male, mean age of 41.49 (+/-9.75) years, most having a family history of substance use (70.97%), and many reporting binge use pattern in last year (49.46%). Baseline assessment revealed 48.7% of the sample was in precontemplation phase for alcohol use and 70% reported severe and persistent craving. This persistent craving was reported by only 15% of the sample by the end of 4 weeks treatment with baclofen (20-40 mg/day). Thirty-four percent of patients reported continued problematic use of alcohol by the end of 4 weeks. CONCLUSION: Our clinical experience suggests that baclofen reduces craving and alcohol consumption including in those with poor motivation. The drug causes few side effects and does not add to the intoxication effect of alcohol. Considering that baclofen is safe in those with liver cirrhosis and reduces withdrawal symptoms due to alcohol, a controlled trial comparing it with standard treatment is required120885* field[33]: year=2016 volume=25 issue=1 spage=11 epage=16 aulast=Rozatkar Not in File?TiRubio, C. Napoleone, G. Luis-González, G. Gutiérrez, A.J. González-Weller, D. Hardisson, A. Revert, C.2017Metals in edible seaweed572-579 Chemosphere173As Asia BIOINDICATOR Cd CONCENTRATIONS Consumption Content DIETARY Dietary intake DOE edible EXPOSURE HEALTH Heavy metal HEAVY METALS Intake LEVELS METALS ORGANIC SEAWEED STUDY toxic Toxic elements 1/12/2017The concentration levels of 20 metals were analyzed by ICP-OES in edible seaweed (Chondrus, Eisenia, Gelidium, Himanthalia, Laminaria, Palmaria, Porphyra, Undaria), from two origins (Asia vs EU) according to their cultivation practices (conventional vs organic). Red seaweed showed higher concentrations of trace and toxic elements. Porphyra may be used as a potential bioindicator for metals. Significant differences were found between the Asian vs European mean contents. The mean Cd level from the conventional cultivation (0.28 mg/kg) was two points higher than the organic cultivation (0.13 mg/kg). A daily consumption of seaweed (4 g/day) contributes to the dietary intake of metals, mainly Mg and Cr. The average intakes of Al, Cd and Pb were 0.064, 0.001 and 0.0003 mg/day, respectively. Based on obtained results, this study suggests that exposure to the toxic metals analyzed (Al, Cd and Pb) through seaweed consumption does not raise serious health concerns, but other toxic metals should be monitored1207053 field[33]: Not in File<?URuiz, N.M. Shapiro, S.E.2017.Caring for young children exposed to marijuana3-9"Advanced Emergency Nursing Journal391ACUTE acute poisoning As CANNABIS case case studies Case Study CHILDREN DATA Environment EXPOSURE INTOXICATION MARIJUANA PAEDIATRIC pediatric Poison POISONING Population Recreational use RESEARCH REVIEW safe STUDY TREATMENT UNITED STATES use1/2017This article reviews the research report, Marijuana Exposure Among Children Younger Than Six Years in the United States (), and, using a case study approach, applies the findings to advanced practice registered nurses. B. extracted data from the National Poison Data System showing an increasing trend in marijuana exposure in children, especially in states where marijuana has been legalized for either medicinal use or recreational use. Advanced practice registered nurses need to be comfortable recognizing and managing marijuana intoxication in the pediatric population, as well as educating parents in providing safe environments for their children120690. field[33]: Not in File B?V;Russell, J.L. Spiller, H.A. Chounthirath, T. Casavant, M.J.2017fPediatric ingestion of vilazodone compared to other selective serotonin reuptake inhibitor medicationsClinical Toxicology0online early: doi: 10.1080/15563650.2017.1287375not published, 03 Mar 17Age analysis As case CHILDREN CLINICAL Clinical outcome COMA DATA EVIDENCE-BASED EXPOSURE FACILITIES Guidelines HEALTH hospitalization Incidence INGESTION IS MANAGEMENT outcome PAEDIATRIC pediatric Poison seizure SEROTONIN SSRIs unintentional vilazodone 2/13/2017]Background: Unintentional ingestion of selective serotonin reuptake inhibitor (SSRI) medications is common amongst children <6 years of age. Current evidence-based management guidelines are based on a low incidence of significant medical outcomes in these children.Objective: To describe and compare outcomes of pediatric exposures to vilazodone with other SSRIs.Methods: A retrospective observational case series analysis of both single and polysubstance SSRI exposures amongst children <6 years old reported to the National Poison Data System (NPDS).Results: 11,384 SSRI exposures in children <6 years of age reported to NPDS between January 2012 and June 2016 were assessed. Vilazodone only accounted for 5.9% of all exposures, but resulted in the highest proportion of health care facility admission compared to other SSRIs, both in single substance (165 of 531 (31.1%); OR 9.0 [7.3–11.2]) and polysubstance (57 of 107 (53.3%); OR 4.1 [2.7–6.2]) exposures. Children exposed to vilazodone also have higher odds of experiencing a major or moderate outcome in single (134 of 531 (25.2%); OR 20.5 [15.5–27.1]) and polysubstance (37 of 107 (35.6%); OR 5.9 [3.7–9.0]) exposures compared to other SSRIs. Several severe clinical outcomes, such as seizure and coma, were more common among the vilazodone exposures.Conclusions: Exposure to vilazodone in this age group results in an increased rate of hospitalization as well as more severe clinical effects as compared to other SSRIs. Current evidence-based SSRI exposure management guidelines may not be appropriate for the management of vilazodone ingestion in this age group121147/ field[33]: Not in File:?WwSanchez-Marin, L. Pavon, F.J. Decara, J. Suarez, J. Gavito, A. Castilla-Ortega, E. Rodriguez de Fonseca, F. Serrano, A.2017Effects of intermittent alcohol exposure on emotion and cognition: a potential role for the endogenous cannabinoid system and neuroinflammation15$Frontiers in Behavioral Neuroscience11ADOLESCENT ADULT ALCOHOL Alcohol use Amygdala Behavior behaviors Binge drinking BRAIN CANNABINOID Cognition cognitive Cognitive deficits COMMUNICATION Emotion ENDOGENOUS ENZYME EXPOSURE GENE EXPRESSION Hippocampus INJECTION INTOXICATION IS LEAD LEVELS MALE MEMORY motor NECROSIS Neuroinflammation NO PROTEIN PSYCHOPATHOLOGY RAT rats RECEPTORS signal tumor tumor necrosis factor-alpha use vulnerability Wistar rat Wistar rats Y2017 Intermittent alcohol exposure is a common pattern of adolescent alcohol use that can lead to binge drinking episodes. Alcohol use is known to modulate the endocannabinoid system (ECS), which is involved in neuronal communication, neuroplasticity, neuroinflammation and behavior. Adolescent male Wistar rats were exposed to 4-week intermittent alcohol intoxication (3 g/kg injections for 4 days/week) or saline (N = 12 per group). After alcohol deprivation, adult rats were assessed for emotionality and cognition and the gene expression of the ECS and other factors related to behavior and neuroinflammation was examined in the brain. Alcohol-exposed rats exhibited anxiogenic-like responses and impaired recognition memory but no motor alterations. There were brain region-dependent changes in the mRNA levels of the ECS and molecular signals compared with control rats. Thus, overall, alcohol-exposed rats expressed higher mRNA levels of endocannabinoid synthetic enzymes (N-acyl-phosphatidylethanolamine phospholipase D and diacylglycerol lipases) in the medial-prefrontal cortex (mPFC) but lower mRNA levels in the amygdala. Furthermore, we observed lower mRNA levels of receptors CB1 CB2 and peroxisome proliferator-activated receptor-alpha in the striatum. Regarding neuropeptide signaling, alcohol-exposed rats displayed lower mRNA levels of the neuropeptide Y signaling, particularly NPY receptor-2, in the amygdala and hippocampus and higher mRNA levels of corticotropin-releasing factor in the hippocampus. Additionally, we observed changes of several neuroinflammation-related factors. Whereas, the mRNA levels of toll-like receptor-4, tumor necrosis factor-alpha, cyclooxygenase-2 and glial fibrillary acidic protein were significantly increased in the mPFC, the mRNA levels of cyclooxygenase-2 and glial fibrillary acidic protein were decreased in the striatum and hippocampus. However, nuclear factor-kappabeta mRNA levels were lower in the mPFC and striatum and allograft inflammatory factor-1 levels were differentially expressed in the amygdala and hippocampus. In conclusion, rats exposed to adolescent intermittent alcohol displayed anxiety-like behavior and cognitive deficits in adulthood and these alterations were accompanied by brain region-dependent changes in the gene expression of the ECS and other signals associated with neuroinflammation and behavior. An intermittent adolescent alcohol exposure has behavioral and molecular consequences in the adult brain, which might be linked to higher vulnerability to addictive behaviors and psychopathologies121015( field[33]: Not in File?XJSantos, C. Olmedo, R.E.2017ESedative-hypnotic drug withdrawal syndrome: recognition and treatment1-20Emergency Medicine Practice193ACID ACUTE acute poisoning Age agent ANTICONVULSANT anticonvulsants Antipsychotic antipsychotics As BACLOFEN BARBITURATE Benzodiazepine BENZODIAZEPINES BETA BETA BLOCKER BETA-BLOCKER Beta-blockers CHRONIC DRUG drugs ETHANOL GAMMA HYDROXYBUTYRIC ACID gamma-butyrolactone GAMMA-HYDROXYBUTYRIC ACID Pathway PHENOBARBITAL POISONING PROPOFOL Reduction Sedatives SYMPTOMS Syndrome THERAPY TOLERANCE TREATMENT use WITHDRAWAL Withdrawal symptoms3/2017uSedative-hypnotic drugs include gamma-Aminobutyric acid (GABA)ergic agents such as benzodiazepines, barbiturates, gamma-Hydroxybutyric acid [GHB], gamma-Butyrolactone [GBL], baclofen, and ethanol. Chronic use of these substances can cause tolerance, and abrupt cessation or a reduction in the quantity of the drug can precipitate a life-threatening withdrawal syndrome. Benzodiazepines, phenobarbital, propofol, and other GABA agonists or analogues can effectively control symptoms of withdrawal from GABAergic agents. Managing withdrawal symptoms requires a patient-specific approach that takes into account the physiologic pathways of the particular drugs used as well as the patient's age and comorbidities. Adjunctive therapies include alpha agonists, beta blockers, anticonvulsants, and antipsychotics. Newer pharmacological therapies offer promise in managing withdrawal symptoms120875C Not in File M?Y%Sarty, K.I. Cowie, A. Martyniuk, C.J.2017The legacy pesticide dieldrin acts as a teratogen and alters the expression of dopamine transporter and dopamine receptor 2a in zebrafish (Danio rerio) embryos37-47IComparative Biochemistry and Physiology Part C: Toxicology & Pharmacology194As CARDIAC DATA DEVELOPMENTAL DIELDRIN DOPAMINE dose edema Embryo ENVIRONMENTAL EXPOSURE IS LEVELS MORTALITY NO pesticide RECEPTORS REMOVAL Testing transcriptomics transporter TREATMENT Tremor WATER Zebrafish2/2/2017Dieldrin (DLD) is a lipophilic pesticide that shows environmental persistence. The objectives were to determine the effects of DLD on GABAergic and dopaminergic systems in developing zebrafish. Both chorionated and dechorionated embryos (~24 hours post-hatch) were exposed to a single concentration of DLD (0.347-3470 muM) for 48 hours. Following exposure, a subset of larvae were placed into clean water for 6 days (i.e. depuration phase). Chorionated embryos showed <15% mortality while dechorionated embryos showed higher mortality (>30%), suggesting that the chorion protected the embryos. Over a 6 day depuration phase, there was a dose dependent effect observed in both the "dechorionated and chorionated embryo" treatments for larval mortality (>60%). At the end of depuration, there was no detectable change in neuro-morphological endpoints that included the ratio of notochord length to body length (%) and the ratio of head area to body area (%). However, DLD did induce cardiac edema, skeletal deformities, and tremors. GABA-related transcripts were not affected in abundance by DLD. Conversely, the relative mRNA levels of dopamine transporter (dat1) and dopamine receptor drd2a mRNA were decreased in dechorionated, but not chorionated, embryos. These data suggest that DLD can alter the expression of transcripts related to dopaminergic signaling. Lastly, GABAA receptor subunits gabrB1 and gabrB2, as well as dopamine receptors drd1 and drd2a, were inherently higher in abundance in dechorionated embryos compared to chorionated embryos. This is an important consideration when incorporating transcriptomics into embryo testing as expression levels can change with removal of the chorion prior to exposure120869, field[33]: Not in File .?Z,Sawade, E. Fabris, R. Humpage, A. Drikas, M.2016PEffect of increasing bromide concentration on toxicity in treated drinking water183-191Journal of Water and Health142ACID BROMIDE BROMINE CHLORINATED CHLORINATION CHRONIC CLIMATE CHANGE COAGULATION CONCENTRATIONS CYTOTOXICITY DBPs DISINFECTANT Disinfection byproducts DISTRIBUTION DRINKING WATER HEALTH Health effects impact IS LEVELS MANAGEMENT MONITORING ORGANIC PLANT plants PRECURSOR PUBLIC PUBLIC HEALTH quality REMOVAL RESEARCH Source SPECIES TEST toxic Toxicities TOXICITY TREATMENT TRIHALOMETHANES WATER2016Research is increasingly indicating the potential chronic health effects of brominated disinfection byproducts (DBPs). This is likely to increase with elevated bromide concentrations resulting from the impacts of climate change, projected to include extended periods of drought and the sudden onset of water quality changes. This will demand more rigorous monitoring throughout distribution systems and improved water quality management at water treatment plants (WTPs). In this work the impact of increased bromide concentration on formation of DBPs following conventional treatment and chlorination was assessed for two water sources. Bioanalytical tests were utilised to determine cytotoxicity of the water post disinfection. Coagulation was shown to significantly reduce the cytotoxicity of the water, indicating that removal of natural organic matter DBP precursors continues to be an important factor in drinking water treatment. Most toxic species appear to form within the first half hour following disinfectant addition. Increasing bromide concentration across the two waters was shown to increase the formation of trihalomethanes and shifted the haloacetic acid species distribution from chlorinated to those with greater bromine substitution. This correlated with increasing cytotoxicity. This work demonstrates the challenges faced by WTPs and the possible effects increasing levels of bromide in source waters could have on public health. Copyright © IWA Publishing 2016120793%<RefMgr field[33]: Not in File?[)Sánchez-Villegas, M.C. Bárcena-Ruiz, A.2017X[Zinc phosphide poisoning in pediatric patients from a Toxicology Center at Mexico City]S44-S527Revista Medica del Instituto Mexicano del Seguro Social 55 Suppl 1Abdominal Pain ACIDOSIS ADOLESCENT Adolescents Age ANTIDOTE As chemical CHILDREN CLINICAL epidemiological EXPOSURE Gender hemodialysis HOME HOSPITAL hypoglycemia HYPOTENSION INTOXICATION IS Knowledge Mechanical ventilation METABOLIC ACIDOSIS method methods Mexico Nausea NO PAEDIATRIC pain PATIENT pediatric pesticide POISONING prevalence RISK RODENTICIDE SOCIAL STUDY suicidal toxic Toxicities TOXICITY TOXICOLOGY VENTILATION Vomiting Y ZINC ZINC PHOSPHIDE2017BACKGROUND: Zinc phosphide is a chemical compound that is frequently used as a rodenticide; it is a highly toxic product that is widely used, among other spaces, at home. Given that it is a highly commercialized pesticide and that there is no antidote, it is mandatory to establish favorably the clinical manifestations of the intoxication. The aim was to describe the epidemiological and clinical profile of children intoxicated with zinc phosphide attended in a toxicological center of a tertiary referral hospital. METHODS: Cross-sectional, retrospective and observational study based on the medical records of 36 pediatric patients attended from 2005 to 2015 at the Centro de Informacion y Atencion Toxicologica from Hospital General "Dr. Gaudencio Gonzalez Garza", which belongs to the Instituto Mexicano del Seguro Social. RESULTS: The study didn't show a prevalence of gender; 66% of patients were children between ages 1 and 2. 96% of patients were healthy and three adolescents used the product with suicidal purposes. Zinc phosphide exposure occurred at home. Toxicity was characterized by hypotension, hypoglycemia, metabolic acidosis, abdominal pain, nausea, and vomiting; none of the patients died. In addition, neither required mechanical ventilation nor hemodialysis. CONCLUSION: The lack of knowledge of the potential toxicity of zinc phosphide and the fact that is easily reached at home allow the exposure to this product; it is an absolutely preventable risk121181+ field[22]: In Spanish with English abstract Not in File B?\Schmidt-Heck, W. Wönne, E.C. Hiller, T. Menzel, U. Koczan, D. Damm, G. Seehofer, D. Knöspel, F. Freyer, N. Guthke, R. Dooley, S. Zeilinger, K.2017vGlobal transcriptional response of human liver cells to ethanol stress of different strength reveals hormetic behavior.Alcoholism, Clinical and Experimental Research%online early: doi: 10.1111/acer.13361not published, 01 Mar 17ACID ALCOHOL ALCOHOLIC As Behavior CELL cluster CONCENTRATIONS dose DOSE-RESPONSE ETHANOL GENE EXPRESSION HEPATITIS HEPATOTOXICITY HUMAN Humans IN VITRO IS LIVER METABOLISM method methods Pathway Regulation STRESS STUDY Toxicities TOXICITY 2/22/2017RBACKGROUND: The liver is the major site for alcohol metabolism in the body and therefore, the primary target organ for ethanol-induced toxicity. In this study, we investigated the in vitro response of human liver cells to different ethanol concentrations in a perfused bioartificial liver device that mimics the complex architecture of the natural organ. METHODS: Primary human liver cells were cultured in the bioartificial liver device and treated for 24 hours with medium containing 150 mM (low), 300 mM (medium) or 600 mM (high) ethanol, while a control culture was kept untreated. Gene expression patterns for each ethanol concentration were monitored using Affymetrix Human Gene 1.0 ST Genechips. Scaled expression profiles of differentially expressed genes (DEGs) were clustered using Fuzzy c-means algorithm. In addition, functional classification methods, KEGG pathway mapping and also a machine learning approach (Random Forest) were utilized. RESULTS: A number of 966 (150 mM ethanol), 1,334 (300 mM ethanol), or 4,132 (600 mM ethanol) genes were found to be differentially expressed. Dose-response relationships of the identified clusters of co-expressed genes showed a monotonic, threshold or non-monotonic (hormetic) behavior. Functional classification of DEGs revealed that low or medium ethanol concentrations operate adaptation processes, while alterations observed for the high ethanol concentration reflect the response to cellular damage. The genes displaying a hormetic response were functionally characterized by over-represented 'cellular ketone metabolism' and 'carboxylic acid metabolism'. Altered expression of the genes BAHD1 and H3F3B was identified as sufficient to classify the samples according to the applied ethanol doses. CONCLUSIONS: Different pathways of metabolic and epigenetic regulation are affected by ethanol exposition and partly undergo hormetic regulation in the bioartificial liver device. Gene expression changes observed at high ethanol concentrations reflect in some aspects the situation of alcoholic hepatitis in humans This article is protected by copyright. All rights reserved120934$ field[33]: Not in FileB?].Schreurs, C.J. van Hoof, J.J. van der Lely, N.2016wHypothermia and acute alcohol intoxication in Dutch adolescents: the relationship between core and outdoor temperaturesJournal of Substance Use0online early: doi: 10.1080/14659891.2016.1235733not published, 20 Feb 17ACUTE ADOLESCENT Adolescents Age ALCOHOL analysis Association Awareness BLOOD Blood alcohol concentration CHILDREN DATA DUTCH Gender HYPOTHERMIA INTENSIVE CARE INTOXICATION IS method methods PAEDIATRIC PATIENT pediatric PREVENTION QUESTIONNAIRE STUDY SURVEILLANCE TEMPERATURE Time2016XPurpose: To investigate hypothermia and its potential association with core and outdoor temperatures in adolescents suffering from acute alcohol intoxication. Methods: Data were derived from the Dutch Pediatric Surveillance System, which monitors alcohol intoxication among all Dutch adolescents. Adolescents < 18 years of age with a positive blood alcohol concentration (BAC > 0 g/l) were included. This resulted in an analysis of data from the years 2011 to 2015 that were obtained through a total of 967 questionnaires. Results: This study revealed small but significantly lower core temperatures in winter time (35.59°C [96.06°F]) versus summer time (35.83°C [96.49°F]). These differences could not be attributed to the genders and ages of the patients. In winter time, 26.6% of the adolescents experienced mild hypothermia, with body temperatures of 32.00-34.99°C (89.60-94.98°F), compared to 18.0% during the summer. Although not significant, amounts of time spent in reduced consciousness, hospitalized and receiving intensive care were prolonged in adolescents with lower core temperatures. Conclusions: This article is the first to describe this trend of hypothermia among alcohol-intoxicated Dutch adolescents admitted during winter time. These findings are important for awareness of this issue and can be used for prevention strategies in the future.120778/ field[33]: Not in File ?^`Schulman, S. Ritchie, B. Nahirniak, S. Gross, P.L. Carrier, M. Majeed, A. Hwang, H.G. Zondag, M.2017sReversal of dabigatran-associated major bleeding with activated prothrombin concentrate: a prospective cohort study44-48Thrombosis Research152)Age ANTICOAGULANT anticoagulants ANTIDOTE ARTERIAL As ASSESSMENT case Cohort Cohort studies Cohort study COMPARISON dabigatran DEATH DOE effectiveness FOLLOW UP Follow-up HOSPITAL Idarucizumab IS NO outcome PATIENT prospective cohort study prothrombin complex concentrate PROTOCOL SAFETY Sex STUDY 2/16/2017&The reversal of dabigatran-associated major bleeding can now be achieved with the antidote idarucizumab. We evaluated activated prothrombin complex concentrate (aPCC) as an alternative for this purpose. Patients treated with dabigatran and suffering a major bleed were treated as per existing hospital protocol with aPCC. They were subsequently recruited for a 30-day follow-up. Effectiveness was evaluated by the treating physician, using an Assessment Guide. Safety outcomes were arterial or venous thromboembolism or death. A comparison was also made with historic cases with dabigatran-associated major bleeds treated with supportive care, by matching 1:2 for type of bleed, age and sex. We aimed at 32 evaluable cases but the study was prematurely discontinued after 14 cases due to the availability of the approved antidote. The effectiveness of aPCC was assessed as Good in 9 (64%), moderate in 5 (36%) and poor in none. There were no thromboembolic events and one death. In the secondary adjudication of effectiveness, using the same criteria and by the same adjudicators as previously done for the historic cases, the outcome was graded for the current cases versus the historic cases as Good, Moderate, or Poor in 10 (71%) versus 16 (57%), 3 (21%) versus 4 (14%), and 1 (7%) versus 8 (29%), respectively. Although supportive care is sufficient to manage many patients with dabigatran-associated bleeding, aPCC might provide an additional benefit to control life-threatening bleeding in selected cases and does not appear to cause an excess of thromboembolic events1211190 field[33]: Not in FileB?_wSegura, A. Herrera, M. Mares, F.R. Jaime, C. Sánchez, A. Vargas, M. Villalta, M. Gómez, A. Gutiérrez, J.M. León, G.2017Proteomic, toxicological and immunogenic characterization of Mexican west-coast rattlesnake (Crotalus basiliscus) venom and its immunological relatedness with the venom of Central American rattlesnake (Crotalus simus)Journal of early: doi: 10.1016/j.jprot.2017.02.015not published, 01 Mar 17VACID ADULT analysis ANTIBODIES ANTIVENOM As biological BOTHROPS Characterization Content DOE ENVENOMATION EVALUATION Hand immunological IN VITRO IN VIVO IS lethal Masked Metalloproteinase Mexico MICE mouse neurotoxic PROTEIN proteins Proteomics RATTLESNAKE SERINE snake bite SNAKEBITE SVMPs TEST toxic Toxicities TOXICITY toxin TOXINS Venom Y 2/23/2017 The venom of the Mexican west-coast rattlesnake (Crotalus basiliscus) was characterized for its protein composition, toxicological profile and immunogenic properties. This venom is composed of 68% Zn2+-dependent metalloproteinases (SVMPs), 14% phospholipases A2 (PLA2s), 11% serine proteinases, 4% SVMPs-inhibitor tripeptides (SVMP-ITs), 2% bradykinin-potentiating peptides (BPPs), 0.6% cysteine-rich secretory proteins (CRISPs), and 0.2% l-amino acid oxidases (LAAOs). SVMPs present in the venom are responsible for azocasein hydrolysis and hemorrhagic activity, but their contribution to the lethal activity of the venom in mice is masked by the neurotoxic activity of PLA2s, which in addition are also responsible for myotoxic activity. Despite its relatively high content of serine proteinases, the venom of C. basiliscus did not exert in vitro coagulant or in vivo defibrinogenating activities. The ability of antivenoms raised against the venoms of C. basiliscus and C. simus (from Costa Rica) to neutralize homologous and heterologous venoms revealed antigenic similarities between toxins of both venoms. Preclinical evaluation of an antivenom produced by using the venom of C. basiliscus as immunogen demonstrated that it is able to neutralize not only the most relevant toxic activities of C. basiliscus venom, but also those exerted by Costa Rican C. simus venom, including coagulant and defibrinogenating activities. BIOLOGICAL SIGNIFICANCE: The Central American rattlesnake (Crotalus simus) is widely distributed from Mexico to west central Costa Rica, and induces an important number of envenomations in this region. On the other hand, the immunogenic mixture used by Laboratorios de Biologicos y Reactivos de Mexico S.A. (Birmex) to produce the snake antivenom more frequently used in Mexico does not include the venom of C. simus. This immunogenic mixture is composed by the venoms of the Fer-de-lance (Bothrops asper) and the Mexican west-coast rattlesnake (Crotalus basiliscus). We studied the protein composition, toxicological profile and immunogenic properties of the venom of C. basiliscus, and evaluated the ability of the Birmex antivenom to neutralize the venom of C. basiliscus and whether it cross-neutralizes the venom of C. simus from Costa Rica. Using proteomics analysis, in combination with in vitro and mouse tests, we determined that the venom of C. basiliscus is mainly composed by SVMPs, which confer proteolytic and hemorrhagic activities to the venom. Other major components of the venom of C. basiliscus are PLA2s, which are responsible for the myotoxic activity and are the main contributors to the lethal activity. Non-clotting SVSPs correspond to 11% of the venom. Minor components include SVMP-ITs, BPPs, CRISPs and LAAOs, which have not been associated with toxicity. The antibodies induced in horses by the venom of C. basiliscus are able to neutralize not only the most relevant toxic activities of the homologous venom, but also those exerted by Costa Rican C. simus venom, including coagulant and defibrinogenating activities. Our preclinical evaluation suggests that Birmex antivenom can be used to treat envenomations by Costa Rican adult C. simus snakebites, despite this venom not being included in the immunizing mixture121060- field[33]: Not in File B?`USergeyev, O. Burns, J.S. Williams, P.L. Korrick, S.A. Lee, M.M. Revich, B. Hauser, R.2017The association of peripubertal serum concentrations of organochlorine chemicals and blood lead with growth and pubertal development in a longitudinal cohort of boys: a review of published results from the Russian Children's StudyReviews on Environmental Health*online early: doi: 10.1515/reveh-2016-0052not published, 01 Mar 174Adverse Age As Association BLOOD Blood lead boys chemical CHEMICALS childhood CHLORINATED Cohort CONCENTRATIONS DATA Development DIOXIN Dioxin-like compound dioxins ENDOCRINE ENVIRONMENTAL Environmental exposure EXPOSURE FURAN GROWTH HEALTH Health effects history HORMONE impact IS LEAD LEVELS Longitudinal longitudinal study MALE Measurement ORGANOCHLORINE Organochlorine pesticides PAEDIATRIC PCBs pesticide PESTICIDES physical examination POLYCHLORINATED BIPHENYLS REMEDIATION RESEARCH REVIEW RUSSIAN SERUM STUDY susceptibility toxic Toxic equivalent Volume WHO 2/23/2017Organochlorine chemicals and lead are environmental exposures that have endocrine disrupting properties (EDCs) which interfere with many aspects of hormone action. Childhood and adolescence are windows of susceptibility for adverse health effects of EDCs. Our ongoing study, the Russian Children's Study (RCS), is one of the few longitudinal studies investigating the impact of EDCs on growth and puberty in boys. It is conducted in the historically contaminated city of Chapaevsk, in the Samara region. The study focuses on evaluating the associations of persistent organochlorine chemicals and lead with growth and pubertal timing. At enrollment in 2003-2005, we collected blood from 516 boys at ages 8-9 years to measure dioxins, furans, polychlorinated biphenyls (PCBs), chlorinated pesticides and lead. At enrollment and at annual visits through the ages of 18-19 years, a physician performed physical examinations that included pubertal staging and testicular volume measurements. We review the history of Chapaevsk as a research site and summarize published RCS data on the association of peripubertal serum concentrations of organochlorines and blood lead levels with growth, pubertal onset and sexual maturity. Overall, we found that persistent organochlorines and lead negatively affected growth during puberty. Our results also suggest that total toxic equivalents (TEQs), dioxin-like compounds, organochlorine pesticides and lead may delay, while nondioxin-like-PCBs may advance, the timing of male puberty. These findings promoted remediation programs in Chapaevsk, with improvement in health indicators, resulting in Chapaevsk being designated a member of the World Health Organization (WHO) network "Healthy Cities" in 2015121109' field[33]: Not in File :?aXSerragui, S. Zalagh, F. Tanani, D.S. Ouammi, L. Moussa, L.A. Badrane, N. Bencheikh, R.S.2016tSuivi thérapeutique pharmacologique de trois médicaments antiépileptiques: retour sur vingt années d'expérience10Pan African Medical Journal25CACID Adverse ADVERSE EFFECTS Age ANTICONVULSANT anticonvulsants Antiepileptic As Association CARBAMAZEPINE case DOSAGE DRUG drugs EPILEPSY IS MANAGEMENT method methods MONITORING Occurrence PATIENT pharmacovigilance PHENOBARBITAL Poison Retrospective study SOCIAL STUDY THERAPEUTIC Therapeutic drug monitoring VALPROIC ACID2016INTRODUCTION: The therapeutic drug monitoring (TDM) of antiepileptic drugs is a tool widely used in the management of epilepsy. In Morocco, this monitoring is carried out by the Centre Anti Poison et Pharmacovigilance (CAPM) since April 1995. METHODS: This is a retrospective study spanning 20 years. It concerns the therapeutic drug monitoring of Phenobarbital (PB) of carbamazepine (CBZ) and valproic acid (VPA). RESULTS: Therapeutic drug monitoring of the 3 antiepileptic drugs represent 58.85% of all applications received by the CAPM. The dosage of PB was ranked first followed by that of CBZ and finally by the VPA. Weak demand for therapeutic drug monitoring in Morocco could be explained by the low number of neurologists in addition to social factors. With its affordable price by patients, PB is the most prescribed antiepileptic drug in our country, which explains the high demand for its dosage. As for the therapeutic drug monitoring of the antiepileptic drug, they were mainly related to age, the occurrence of adverse effects, the association antiepileptic drugs or in the case of verification of patient compliance. CONCLUSION: Efforts are required for promoting the interests of therapeutic drug monitoring of antiepileptic drug in the management of epilepsy in Morocco120802/ field[22]: [Therapeutic drug monitoring of three antiepileptic drugs - back on twenty years of experience]. In French with English abstract RefMgr field[33]: Not in FileB?b9Sethi, T.K. Basdag, B. Bhatia, N. Moslehi, J. Reddy, N.M.2017Beyond anthracyclines: preemptive management of cardiovascular toxicity in the era of targeted agents for hematologic malignancies&Current Hematologic Malignancy Reports,online early: doi: 10.1007/s11899-017-0369-ynot published, 01 Mar 17Adverse adverse event Adverse events Age agent As CARDIOTOXICITY CARDIOVASCULAR Cardiovascular side effects Cardiovascular toxicity CHRONIC chronic myeloid leukemia DATA DRUG Drug discovery drugs EXPOSURE Incidence IS leukemia Long term Long-term LYMPHOMA MANAGEMENT MONITORING multiple myeloma MYELOMA non-Hodgkin lymphoma PATIENT Population proteasome REVIEW Side effect side effects side-effects Toxicities TOXICITY TREATMENT use 2/23/2017Advances in drug discovery have led to the use of effective targeted agents in the treatment of hematologic malignancies. Drugs such as proteasome inhibitors in multiple myeloma and tyrosine kinase inhibitors in chronic myeloid leukemia and non-Hodgkin lymphoma have changed the face of treatment of hematologic malignancies. There are several reports of cardiovascular adverse events related to these newer agents. Both "on-target" and "off-target" effects of these agents can cause organ-specific toxicity. The need for long-term administration for most of these agents requires continued monitoring of toxicity. Moreover, the patient population is older, often over 50 years of age, making them more susceptible to cardiovascular side effects. Additional factors such as prior exposure to anthracyclines often add to this toxicity. In light of their success and widespread use, it is important to recognize and manage the unique side effect profile of targeted agents used in hematologic malignancies. In this article, we review the current data for the incidence of cardiovascular side effects of targeted agents in hematologic malignancies and discuss a preemptive approach towards managing these toxicities120975+ field[33]: Not in File B?cHSettimi, L. Giordano, F. Lauria, L. Celentano, A. Sesana, F. Davanzo, F.2017NSurveillance of paediatric exposures to liquid laundry detergent pods in ItalyInjury Prevention1online early: doi: 10.1136/injuryprev-2016-042263not published, 28 Feb 18Age Aged CHILDREN CLINICAL COMPARISON DETERGENT DETERGENTS EXPOSURE HOSPITAL IS laundry detergent method methods NO outcome PACKAGING PAEDIATRIC PATIENT Poison SAFETY SEVERITY STUDY SURVEILLANCE Time trends UNIT UNITS 2/10/2017OBJECTIVE: To analyse paediatric exposures to pod and traditional laundry detergents in Italy and changes in exposure trends. METHODS: Analyses of a series of patients aged <5 years and exposed to laundry detergents between September 2010 and June 2015, identified by the National Poison Control in Milan. RESULTS: In comparison with patients exposed to traditional laundry detergents (n=1150), a higher proportion of those exposed to pods (n=1649) were managed in hospital (68% vs 42%), had clinical effects (75% vs 22%) and moderate/high severity outcomes (13% vs <1%). Exposure rates were stable over time for traditional detergents (average 0.65 cases/day), but an abrupt decline in major company pods was seen in December 2012, 4 months after the introduction of opaque outer packaging (from 1.03 to 0.36 cases/day and from 1.88 to 0.86 cases/million units sold). The odds of clinical effects was higher for exposure to pods than for traditional detergents (OR=10.8; 95% CI 9.0 to 12.9). Among patients exposed to pods, the odds of moderate/high severity outcomes was four times higher for children aged <1 years than for the other age groups (OR=3.9; 95% CI 2.2 to 7.0). Ten children exposed to laundry detergent pods had high severity outcomes while no children exposed to traditional laundry detergents developed high severity effects. CONCLUSIONS: The study confirms that exposure to laundry detergent pods is more dangerous than exposure to traditional detergents. In Italy, 4 months after the introduction of opaque outer packaging by a major company, product-specific exposure rates decreased sharply, suggesting that reducing visibility of laundry detergent pods may be an effective preventive measure. Further efforts are needed to improve safety1208860 field[33]: Not in File|B?d<Shafer, E. Bergeron, N. Smith-Ray, R. Robson, C. O'Koren, R.2017;A nationwide pharmacy chain responds to the opioid epidemic/Journal of the American Pharmacists Association-online early: doi: 10.1016/j.japh.2016.12.075not published, 28 Feb 17ABUSE burden dispensing EDUCATION EPIDEMIC EVALUATION HEALTH history impact INTERACTION IS Mental health NALOXONE OPIOID Opioid overdose Opioids OVERDOSE PATIENT PREVENTION PUBLIC PUBLIC HEALTH quality RISK safe SERVICE SUBSTANCE ABUSE2/2/2017QOBJECTIVES: To describe the 3-pronged approach taken by a large national retail pharmacy chain to address the opioid epidemic and associated overdoses. SETTING: Large national retail pharmacy chain with more than 8200 stores in 50 states. PRACTICE DESCRIPTION: Eight million customer interactions daily through in-store and digital settings. This is a company with a long history of responding to public health crises. PRACTICE INNOVATION: Initiated 3 programs to respond to the opioid crisis: 1) provide safe medication disposal kiosks; 2) expand national access to naloxone; and 3) provide education on the risk and avoidance of opioid overdose. Used the RE-AIM framework to evaluate and enhance the quality, speed, and public health impact of the interventions. EVALUATION: Not applicable. RESULTS: Early results are safe medication disposal kiosks in more than 43 states, naloxone-dispensing program in 33 states, and patient and support system education using the Opioid Overdose Toolkit from the Substance Abuse and Mental Health Services Administration. CONCLUSION: The availability of safe drug-disposal kiosks, naloxone dispensing at pharmacies, and patient education are key prevention initiatives to address the opioid epidemic and reduce the increasing national burden of opioid overdose. Early results are quantitatively and qualitatively promising120893, field[33]: Not in File0?eFShanker, K. Mohan, G.K. Hussain, M.A. Jayarambabu, N. Pravallika, P.L.2017Green biosynthesis, characterization, in vitro antidiabetic activity, and investigational acute toxicity studies of some herbal-mediated silver nanoparticles on animal models188-192Pharmacognosy Magazine1349ACUTE Acute toxicity analysis ANIMAL animal models As ASSAY biological biosynthesis CELL Characterization chemical DATA Development DIABETES FEMALE hyperglycemia IN VITRO IN VIVO Inhibition INSULIN IS LATE LIPID METABOLISM method methods MICE MODEL mouse NANOPARTICLES NITRATE ORAL PLANT plants PROTEIN PSORALEA RESEARCH safe SAFETY SILVER Silver nanoparticles SILVER NITRATE Source STUDY Synthesis TECHNIQUE toxic toxic effects Toxicities TOXICITY Toxicity study US X-RAY1/2017 Diabetes is a metabolic disorder characterized by hyperglycemia, altered carbohydrate, lipid and protein metabolism. In recent studies, Nanoscience and nanotechnology are blazing fields for researchers; for researchers; of late there has been a prodigious excitement in the field of nanopharmacology to study silver nanoparticle (SNP) synthesis using natural products. Biological methods have been used to synthesize SNPs using medicinally active plants having an antidiabetic role, and this made us to assess the biologically synthesized SNPs from the seed extract of Psoralea corylifolia using 1 mM silver nitrate solution. The synthesized herbal-mediated SNPs (HMSNPs) were subjected to various characterization techniques such as X-ray diffraction analysis (XRD), energy dispersive X-ray (EDX) analysis, transmission electron microscope (TEM), and differential light scattering (DLS), respectively. In the current study the HMSNPs were tested to observe the in vitro antidiabetic activity and possible toxic effects in healthy female albino mice by following OECD guidelines-425. Huge data from biochemical, cellular, mouse, and chemical inhibitor studies have recognized protein tyrosine phosphatase 1B (PTP1B) as a major negative regulator of insulin signaling. In addition, corroboration suggests that insulin action can be enhanced by the inhibition of PTP1B. Keeping in view of the above fact, the PTP1B assay was done to determine the PTP1 B inhibitory effect of HMSNPs. It can be concluded that medicinal plants can be a good source for the synthe sis of HMSNPs. This study can be used for the development of valuable nanomedicines to treat various ailments, and it also highlights the safety and biocompatibility of SNPs within a biological cell; in vivo parameters need to be considered for further discoveries. SUMMARY: In present research, acute oral toxicity studies and in vitro anti diabetic activity of Herbal mediated silver nanoparticles (HMSNPs) has been investigated. Characterization techniques employed to determine the Crystallanity, size, shape and elemental composition of HMSNPs. The results obtained from acute oral toxicity studies and histopathological studies showed that the synthesized HMSNPs were non-toxic and safe. and also had good in vitro anti diabetic activity. The results would provide certain references to screen out more pharmacological activities of silver nanoparticles using green biosynthesis methods. Abbreviations used: HMSNPs: Herbal mediated silver nanoparticles, XRD: X-ray diffraction, EDX: Energy dispersive X-ray analysis, TEM: Transmission electron microscope, PTP1B: Protein tyrosine phosphotase 1B, OECD: Organization for economic cooperation and development121090- field[33]: Not in File ?fShao, L. Zhang, L. Zhen, Z.2017Interrupted time series analysis of children's blood lead levels: a case study of lead hazard control program in Syracuse, New Yorke0171778PLoS ONE1221analysis biomonitoring BLOOD Blood lead case case studies Case Study CHILDREN CONCENTRATIONS COST DATA HAZARD impact LEAD Lead Poisoning LEVELS Long term Long-term MODEL PAEDIATRIC PAINT POISONING PREVENTION Reduction SOIL Source STUDY SURVEILLANCE TEMPORAL Time time series TREATMENT trends UNITED STATES2017wChildren's blood lead concentrations have been closely monitored over the last two decades in the United States. The bio-monitoring surveillance data collected in local agencies reflected the local temporal trends of children's blood lead levels (BLLs). However, the analysis and modeling of the long-term time series of BLLs have rarely been reported. We attempted to quantify the long-term trends of children's BLLs in the city of Syracuse, New York and evaluate the impacts of local lead poisoning prevention programs and Lead Hazard Control Program on reducing the children's BLLs. We applied interrupted time series analysis on the monthly time series of BLLs surveillance data and used ARMA (autoregressive and moving average) models to measure the average children's blood lead level shift and detect the seasonal pattern change. Our results showed that there were three intervention stages over the past 20 years to reduce children's BLLs in the city of Syracuse, NY. The average of children's BLLs was significantly decreased after the interventions, declining from 8.77mug/dL to 3.94mug/dL during1992 to 2011. The seasonal variation diminished over the past decade, but more short term influences were in the variation. The lead hazard control treatment intervention proved effective in reducing the children's blood lead levels in Syracuse, NY. Also, the reduction of the seasonal variation of children's BLLs reflected the impacts of the local lead-based paint mitigation program. The replacement of window and door was the major cost of lead house abatement. However, soil lead was not considered a major source of lead hazard in our analysis120919. field[33]: Not in File?gJShaw, W.2017Elevated urinary glyphosate and clostridia metabolites with altered dopamine metabolism in triplets with autistic spectrum disorder or suspected seizure disorder: a case study50-57Integrative Medicine161ACID ANIMAL As author AUTISM BACTERIA case case studies Case Study chemical CHEMICALS CHILDREN Correlates CREATININE DATA DIET DOPAMINE ENVIRONMENTAL ENZYME epidemiological EXPOSURE family FEMALE FOOD GASTROINTESTINAL genetic GLYPHOSATE HI HUMAN Inhibition IS Laboratories LABORATORY MALE METABOLISM METABOLITE Metabolites MITOCHONDRIA Modified Mutation Mutations ORGANIC Organic food outcome Phenolic compounds seizure SPECIES STUDY TEST Testing toxic urinary URINE USAGE use WHO2/2017% CONTEXT: Autism is a neurodevelopmental disorder for which a number of genetic, environmental, and nutritional causes have been proposed. Glyphosate is used widely as a crop desiccant and as an herbicide in fields of genetically modified foods that are glyphosate resistant. Several researchers have proposed that it may be a cause of autism, based on epidemiological data that correlates increased usage of glyphosate with an increased autism rate. OBJECTIVE: The current study was intended to determine if excessive glyphosate was present in the triplets and their parents and to evaluate biochemical findings for the family to determine the potential effects of its presence. DESIGN: The author performed a case study with the cooperation of the parents and the attending physician. SETTING: The study took place at The Great Plains Laboratory, Inc (Lenexa, KS, USA). PARTICIPANTS: Participants were triplets, 2 male children and 1 female, and their parents. The 2 male children had autism, whereas the female had a possible seizure disorder. All 3 had elevated urinary glyphosate, and all of the triplets and their mother had elevated values of succinic acid or tiglylglycine, which are indicators of mitochondrial dysfunction. INTERVENTION: The participants received a diet of organic food only. OUTCOME MEASURES: The study performed organic acids, glyphosate, toxic chemicals and tiglylglycine, and creatinine testing of the participants' urine. RESULTS: The 2 male triplets with autism had abnormalities on at least 1 organic acids test, including elevated phenolic compounds such as 4-cresol, 3-[3-hydroxyphenyl]-3-hydroxypropionic acid and 4-hydroxyphenylacetic acid, which have been previously associated with Clostridia bacteria and autism. The female, who was suspected of having a seizure disorder but not autism, did not have elevated phenolic compounds but did have a significantly elevated value of the metabolite tiglylglycine, a marker for mitochondrial dysfunction and/or mutations. One male triplet was retested postintervention and was found to have a markedly lower amount of glyphosate in his urine. CONCLUSIONS: The pattern of metabolites in the urine samples of the males with autism are consistent with a recent theory of autism that connects widespread glyphosate use with alteration of animal and human gastrointestinal flora. That theory is that the normally beneficial bacteria species that are sensitive to glyphosate are diminished and harmful bacteria species, such as Clostridia, that are insensitive to glyphosate, are increased following exposure to glyphosate. Excessive dopamine, caused by inhibition of dopamine-beta-hydroxylase by Clostridia metabolites, in turn, produces oxidative species that damage neuronal Krebs cycle enzymes, neuronal mitochondria, and neuronal structural elements such as the neurofibrils121032: Not in File B?hdShi, Q. Boots, A.W. Maas, L. Veith, C. van Kuijk, K. Haenen, G.R. Godschalk, R.W. van Schooten, F.J.2017gEffect of Interleukin (IL)-8 on benzo[a]pyrene metabolism and DNA damage in human lung epithelial cells Toxicology,online early: doi: 10.1016/j.tox.2017.02.013not published, 01 Mar 17Benzo[a]pyrene carcinogenic CELL chemical CONCENTRATIONS CYP1A1 CYTOCHROME CYTOCHROME P450 cytokine DNA DNA DAMAGE ENZYME EXPOSURE GENE EXPRESSION GLUTATHIONE GSH HUMAN INFLAMMATION LEVELS LUNG METABOLISM METABOLITE NADPH NO P450 PULMONARY TREATMENT 2/23/2017PIt has been well established that inflammation and concurrent mutagenic exposures drive the carcinogenic process in a synergistic way. To elucidate the role of the inflammatory cytokine IL-8 in this process, we studied its effect on the activation and deactivation of the chemical mutagen benzo[a]pyrene B[a]P in the immortalized pulmonary BEAS-2B cell line. After 24hours incubation with B[a]P in the presence or absence of IL-8, the B[a]P induced cytochrome P450 1A1 and 1B1 (CYP1A1 and CYP1B1) gene expression and CYP1A1 enzyme activity was significantly higher in the presence of the cytokine. Consistent with these findings, we observed higher concentration of the metabolite B[a]P-7,8-diol under concurrent IL-8 treatment conditions. Interestingly, we also found higher concentrations of unmetabolized B[a]P. To explain this, we examined the downstream effects of IL-8 on NADPH oxidases (NOXes). IL-8 lowered the intracellular NADPH level, but this effect could not explain the changes in B[a]P metabolism. IL-8 also significantly depleted intracellular glutathione (GSH), which also resulted in enhanced levels of unmetabolized B[a]P, but increased concentrations of the metabolite B[a]P-7,8-diol. No differences in B[a]P-DNA adducts level were found between B[a]P and B[a]P combined with IL-8, and this might be due to a 3-fold increase in nucleotide excision repair (NER) after IL-8 treatment. These findings suggest that IL-8 increased the formation of B[a]P-7,8-diol despite an overall delayed B[a]P metabolism via depletion of GSH, but DNA damage levels were unaffected due to an increase in NER capacity121131+ field[33]: Not in File?i(Shi, X.T. Chen, L.M. Wang, S.J. Tian, Y.2017G[Human exposure and thyroid toxicity of polybrominated diphenyl ethers]188-192Zhonghua Yu Fang Yi Xue Za Zhi512AIR analog ANIMAL As chemical CHEMICALS construction DIPHENYL DIPHENYL ETHER DUST ENDOCRINE Endocrine Disruption Endocrine System ENVIRONMENTAL Ether ETHERS EXPOSURE FLAME RETARDANT FOOD HORMONE hormones HUMAN IMMUNE SYSTEM impact LATE LEVELS LIVER MECHANISM Mechanisms PAPER PBDEs POLYBROMINATED DIPHENYL ETHERS REPRODUCTION RESEARCH REVIEW STUDY thyroid Thyroid hormone THYROID HORMONES TISSUE Toxicities TOXICITY USAGE WATER2/6/2017 Polybrominated diphenyl ethers (PBDEs), a kind of important Brominated Flame Retardant (BFR), are widely used in electronic products, construction materials and textiles. PBDEs have been detected in many environmental media (including air, water, dust, sediment and food), many animal and human tissues. For their environmental persistence, high bioaccumulative and multiple biotoxicitiies, PBDEs have been viewed as one of the most concerned environmental Endocrine Disrupting Chemicals (EDCs) at present. Although detailed mechanisms are not clear, studies have found that PBDEs can induce toxicity to liver, endocrine system, nervous system, reproduction and immune system. What's more, lots of experiments indicate that PBDEs exposure can alter the levels of thyroid hormones. Recently, studies on the impact of PBDEs exposure on thyroid hormones have been quite a few and have not reached an agreement, especially on the alternation of thyroid hormones caused by PBDEs exposure, which has also been a hot issue. This paper reviews from the basic properties, usage, exposure and biotoxicity of PBDEs. We mainly introduce the impact PBDEs have on the thyroid and thyroid hormones in terms of biotoxicity, and attach importance to the endocrine disruption and neurodeveloptoxicity. We also give a preliminary introduction to hydroxylated and methoxylated polybrominated diphenyl ethers, structural analogs of PBDEs, which researchers start late to study. This paper can be a reference for the further research on PBDEs exposure and biotoxicity121184+ field[22]: In Chinese with English abstract Not in FileB?jJ(Shively, R.M. Hoffman, R.S. Manini, A.F.2017tResponse to Juurlink letter: comment on Shively et al. "Acute salicylate poisoning: risk factors for severe outcome"Clinical Toxicology0online early: doi: 10.1080/15563650.2017.1296155not published, 03 Mar 17ACUTE ADULT Age analysis As COMA LACTATE LETTER outcome PATIENT POISONING RESPIRATORY RISK Risk factor RISK FACTORS SALICYLATE STUDY 2/28/2017121157/ field[33]: Not in File ?k>Shoaei, S.D. Sistanizad, M. Mozafari, N. Alinia, T. Talaie, H.2016The overestimation of vancomycin-associated nephrotoxicity: the effect of rhabdomyolysis and nephrotoxicants at a referral poison center, Tehran, Irane39969$Iranian Red Crescent Medical Journal1810qAge As baseline DATA FAILURE HOSPITAL INFECTION Infections injuries Injury INTENSIVE CARE intensive care unit IS Laboratories LABORATORY MALE method methods NEPHROTOXICITY NO OPIOID Opioids PATIENT PNEUMONIA Poison POISONING RESEARCH Retrospective study RHABDOMYOLYSIS RISK Risk factor RISK FACTORS STAPHYLOCOCCUS AUREUS STUDY THERAPY Time TREATMENT UNIT VANCOMYCIN WHO2016TBackground: Vancomycin is a first-line therapy for infections due to Methicillin-Resistant Staphylococcus aureus (MRSA). Nephrotoxicity subsequent to vancomycin administration has been discussed in many previous researches. Objectives: The present study aimed to determine the nephrotoxic potential of vancomycin among ventilator-associated pneumonia (VAP) poisoned patients after restricting the effect of risk factors such as rhabdomyolysis and other nephrotoxicants. Methods: This two-year cross-sectional retrospective study was conducted among VAP patients,who received vancomycin at the toxicological intensive care unit of Loghman Hakim hospital of Iran from 2013 to 2015. Baseline and laboratory data of eligible patients were extracted from medical records. Nephrotoxicity was defined based on the risk,injury,failure,loss,and end state (RIFLE) criteria. Results: One hundred and fifty-four VAP patients' profiles were reviewed,of whom 110 were eligible. The median age was 33.50 (12 to 94) years and 73.6% were male. The median time interval between poisoning and admission was four (0 to 48) hours. The most common cause of poisoning was opioids (33%). Ten patients developed new-onset nephrotoxic event,including four in risk,four in injury and two in failure class. Median vancomycin treatment time until a nephrotoxic event was three days. There was no significant difference between those who developed nephrotoxicity compared to those who did not except median vancomycin trough level (14.5 in nephrotoxic versus 13.7 in non-nephrotoxic,P = 0.007). Conclusions: The result of this study indicated that nephrotoxicity rate among patients treated with vancomycin is under the influence of the poisoning by nephrotoxicants. Higher vancomycin trough level was associated with increasing nephrotoxicity rate. Copyright © 2016,Iranian Red Crescent Medical Journal120830% field[33]: Not in File B?l)Sidhu, M.K. Ravindra, K. Mor, S. John, S.2017XHousehold air pollution from various types of rural kitchens and its exposure assessment Science of the Total Environment2online early: doi: 10.1016/j.scitotenv.2017.01.051not published, 01 Mar 17hAGRICULTURAL AIR AIR POLLUTION analysis ASSESSMENT Biomass carbon CARBON MONOXIDE CHILDREN CO CONCENTRATIONS ENVIRONMENTAL EVALUATION EXPOSURE EXPOSURE ASSESSMENT GA GAS HAZARD HEALTH Health risk Health risks HOUSEHOLD Household air pollution INDOOR Intake particulate Particulate matter PM2.5 Pollutant POLLUTION RISK Rural t TEMPERATURE TEMPORAL Time use WHO 2/13/2017Exposure to household air pollutants has become a leading environmental health risk in developing countries. Considering this, real-time temporal variation in fine particulate matter (PM2.5) and carbon monoxide (CO) concentrations were measured in various types of rural household kitchens. Observed average concentrations of PM2.5, CO, percent relative humidity (%RH) and temperature (T) in five different kitchen types were 549.6mug/m3, 4.2ppm, 70.2% and 20 degrees C respectively. Highest CO and PM2.5 concentration were found in household performing cooking in indoor kitchens (CO: 9.3ppm; PM2.5: 696.5mug/m3) followed by outdoor kitchens (CO: 5.8ppm; PM2.5: 539.5mug/m3). The concentration of PM2.5 and CO varied according to the fuel type and highest concentration was observed in kitchens using cowdung cakes followed by agricultural residue>firewood>biogas>Liquefied Petroleum Gas (LPG). Results revealed that the pollutants concentration varied with kitchen type, fuel type and the location of kitchen. An exposure index was developed to calculate the exposure of cook, non-cook and children below 5years. Analysis of exposure index values shows that cooks, who use solid biomass fuel (SBF) in indoor kitchen, are four times more exposed to the harmful pollutants than the cooks using clean fuel. Further, using indoor PM2.5 concentrations, hazard quotient was calculated based on evaluation of intake concentration and toxicological risk, which also shows that SBF users have higher health risks (hazard quotient>1) than the clean fuel (LPG) users1211131 field[33]: Not in File$?mJ?Silfeler, I. Alp, H. Dorum, B.A. Nacar, E. Arslan, S. Uygur, V.2016LProtective effect of ellagic acid on paraquat-induced kidney hazards in rats23-28"Iranian Journal of Kidney Diseases111ACID ANIMAL ANTIDOTE As case CLINICAL COMPARISON DETOXIFICATION dose ELLAGIC ACID glomerular HAZARD HUMAN IS KIDNEY method methods NEPHROTOXICITY P PARAQUAT RAT rats safe STUDY TISSUE toxic TREATMENT1/2016INTRODUCTION: Paraquat is a commonly used highly toxic herbicide. Despite many studies on detoxification of paraquat, an efficient and safe antidote has not been introduced for toxic cases in human being. The aim of this study was to investigate the effect of ellagic acid (EA) on paraquat-induced kidney hazards in rats. MATERIALS AND METHODS: Sixty rats were randomly assigned as controls and 5 treatment groups (n = 10 each) receiving EA only, paraquat at doses of 15 mg/kg and 45 mg/kg, and paraquat at the same doses plus EA. Paraquat was intraperitoneally injected and the EA was orally given. Kidney tissues were stained with hematoxylin-eosin for histopathologic investigation. RESULTS: Pathologic scoring showed that paraquat at the higher dose was associated with higher scores than the in the controls, EA group, and the high-dose paraquat group with EA treatment (P < .001 for all comparisons). It was noted that paraquat caused a serious damage in the kidney and the EA treatment significantly reduced the extent of the damage. CONCLUSIONS: This study showed the protective effects of EA against paraquat-induced nephrotoxicity histologically. Ellagic acid provided significant improvement in glomerular and tubular structure1208928 Not in FileVB?n3Slagboom, J. Kool, J. Harrison, R.A. Casewell, N.R.2017jHaemotoxic snake venoms: their functional activity, impact on snakebite victims and pharmaceutical promiseBritish Journal of Haematology$online early: doi: 10.1111/bjh.14591not published, 01 Mar 17As BLOOD BLOOD PRESSURE DISEASE HAEMORRHAGE HUMAN impact IS Long term Long-term Medicine MORBIDITY neurotoxic PATHOLOGY Potency PROTEIN proteins REVIEW selectivity snake bite SNAKE VENOM SNAKEBITE Snakes SPECIES THERAPEUTIC toxic use Venom 2/24/2017(Snake venoms are mixtures of numerous proteinacious components that exert diverse functional activities on a variety of physiological targets. Because the toxic constituents found in venom vary from species to species, snakebite victims can present with a variety of life-threatening pathologies related to the neurotoxic, cytotoxic and haemotoxic effects of venom. Of the 1.8 million people envenomed by snakes every year, up to 125 000 die, while hundreds of thousands survive only to suffer with life-changing long-term morbidity. Consequently, snakebite is one of the world's most severe neglected tropical diseases. Many snake venoms exhibit strong haemotoxic properties by interfering with blood pressure, clotting factors and platelets, and by directly causing haemorrhage. In this review we provide an overview of the functional activities of haemotoxic venom proteins, the pathologies they cause in snakebite victims and how their exquisite selectivity and potency make them amenable for use as therapeutic and diagnostic tools relevant for human medicine120954# field[33]: Not in FileB?o)Soni, M. Prakash, C. Sehwag, S. Kumar, V.2017]Protective effect of hydroxytyrosol in arsenic-induced mitochondrial dysfunction in rat brain/Journal of Biochemical and Molecular Toxicology$online early: doi: 10.1002/jbt.21906not published, 01 Mar 17agent ARSENIC ARSENITE As BRAIN CATALASE EXPOSURE Hydroxytyrosol IV LEVELS MITOCHONDRIA mRNA expression NEUROTOXICITY PROTEIN proteins RAT rats SODIUM SODIUM ARSENITE STUDY SUPEROXIDE SUPEROXIDE DISMUTASE TREATMENT 2/22/2017The present study was planned to investigate the protective effect of hydroxytyrosol (HT) against arsenic (As)-induced mitochondrial dysfunction in rat brain. Rats exposed to sodium arsenite (25 ppm for 8 weeks) showed decreased mitochondrial complexes (I, II, IV) activities, mitochondrial superoxide dismutase (MnSOD), and catalase activities in brain mitochondria. As-treated rats showed reduced mRNA expression of complex I (ND-1, ND-2), IV (COX-1, COX-4) subunits, and uncoupling protein-2 (UCP-2). In addition to this, As exposure downregulated the protein expression of MnSOD. Administration of HT with As restored the enzymatic activities of mitochondrial complexes, MnSOD and catalase, increased the mRNA levels of complexes subunits and UCP-2 as well as proteins level of MnSOD. These results suggest that HT efficiently restores mitochondrial dysfunction in As neurotoxicity and might be used as potential mitoprotective agent in future121039# field[33]: Not in File n?pYSonthalia, N. Pawar, S.V. Mohite, A.R. Jain, S.S. Surude, R.G. Rathi, P.M. Contractor, Q.2016gMetronidazole-induced encephalopathy in alcoholic liver disease: a diagnostic and therapeutic challengee79-e83Journal of Emergency Medicine514ACUTE ALCOHOLIC As BLOOD BRAIN case CASE REPORT Case-report CEREBELLAR ATAXIA CEREBROSPINAL FLUID cirrhosis CLEARANCE CLINICAL clinical symptoms CONFUSION discontinuation DISEASE dose DRUG Emergencies emergency EMERGENCY DEPARTMENT ENCEPHALOPATHY FAILURE HEPATIC Imaging IS LIVER LIVER CIRRHOSIS LIVER DISEASE Liver failure MAGNETIC RESONANCE magnetic resonance imaging METABOLITE METRONIDAZOLE metronidazole-induced encephalopathy MRI PATIENT recovery reversible SYMPTOMS THERAPEUTIC Toxicities TOXICITY use WHO20160Background Acute encephalopathy in a patient with alcoholic liver disease (ALD) is a commonly encountered emergency situation occurring most frequently due to liver failure precipitated by varying etiologies. Acute reversible cerebellar ataxia with confusion secondary to prolonged metronidazole use has been reported rarely as a cause of encephalopathy in patients with ALD. Case Report We describe a decompensated ALD patient with recurrent pyogenic cholangitis associated with hepatolithiasis who presented to the emergency department with sudden-onset cerebellar ataxia with dysarthria and mental confusion after prolonged use of metronidazole. Magnetic resonance imaging (MRI) of the brain was suggestive of bilateral dentate nuclei hyper intensities on T2 and fluid-attenuated inversion recovery sections seen classically in metronidazole-induced encephalopathy (MIE). Decompensated liver cirrhosis resulted in decreased hepatic clearance and increased cerebrospinal fluid concentration of metronidazole leading to toxicity at a relatively low total cumulative dose of 22 g. Both the clinical symptoms and MRI brain changes were reversed at 7 days and 6 weeks, respectively, after discontinuation of metronidazole. Why Should an Emergency Physician Be Aware of This? A patient with ALD presenting with encephalopathy creates a diagnostic dilemma for the emergency physician regarding whether to continue metronidazole and treat for hepatic encephalopathy or to suspect for MIE and withhold the drug. Failure to timely discontinue metronidazole may worsen the associated hepatic encephalopathy in these patients. Liver cirrhosis patients have higher mean concentration of metronidazole and its metabolite in the blood, making it necessary to keep the cumulative dose of metronidazole to < 20 g in them. Copyright © 2016 Elsevier Inc1207770 field[33]: Not in FileB?q"Sood, S.B. Banner, W. Barton, R.P.2017MExtracorporeal cardiopulmonary resuscitation after brown recluse envenomationClinical Toxicology0online early: doi: 10.1080/15563650.2017.1287913not published, 03 Mar 17ACUTE acute poisoning CARDIOPULMONARY Cardiopulmonary Resuscitation ENVENOMATION extracorporeal LETTER POISONING RESUSCITATION SPIDER TREATMENT2/9/2017121176/ field[33]: Not in File C?r!Sotelo-Cruz, N. Gómez-Rivera, N.2017;A retrospective review of rattlesnake bites in 100 children121-128Minerva Pediatrica692RAge As case CHILDREN CLINICAL complications ENVENOMATION EPIDEMIOLOGY FASCIOTOMY Gender HOME hospitalization INFECTION Infections INTOXICATION IS MALE method methods Mexico MORTALITY NEUROLOGICAL PAEDIATRIC PATIENT POISONING RATTLESNAKE REVIEW Rural SEQUELAE SERUM snake bite SNAKEBITE Snakes SPECIES SYMPTOMS THERAPY Time TREATMENT Venom4/2017BACKGROUND: A retrospective review of clinical features and treatment of children hospitalized for rattlesnake bite. METHODS: One hundred clinical records were reviewed. Variables included: age, gender, season of the year, signs, symptoms, poisoning grade, complications, treatment and sequelae. RESULTS: Fifty-nine percent were males and 37% were less than 5 years of age; 87% occurred in rural areas; 63% of the snakebites occurred during the summer, of them, 39% occurred within the perimeter of the domicile and 8% within the home. Sixty-seven percent of children bitten by snakes reached the second degree of envenomation. During the first period (1977-1996), treatment for intoxication included treatment with polyvalent equine anti-snake venom serum. During the second period (1997-2014, a polyvalent polyclonal horse anti-snake venom F(Ab) was used. The second period hospitalization time was reduced to 3.9 days (P<0.0001). Hematological complications dominated during the first period (P=0.093) with wound infections occurring in 26% of the cases, neurological symptoms in 24 %, fasciotomy in 6% and mortality in 1%. The second degree poisoning was more frequent and was more severe in 7% of the patients. It was determined that the best treatment for snakebite was F(Ab') 2 therapy. Mortality occurred in 1% of the cases. CONCLUSIONS: Rattlesnake (Crotalus sp.) bite, in Mexico is less frequent as compared to other crotalidae species. The hematological complications are more frequent. We did not observe any recurrent phenomenons1209070 field[33]: Not in File?sSoyka, M. Preuss, U. Hoch, E.2017Cannabisinduzierte Störungen311-325 Nervenarzt883ADULT As CANNABIS CHRONIC chronic pain cognitive dependence evidence GERMAN IS marihuana medical use MISUSE NO pain Population PREVENTION PROTOCOL PSYCHIATRIC psychiatric disorder PSYCHOLOGICAL SYMPTOMS Syndrome THERAPY Toxicities TOXICITY use WITHDRAWAL Withdrawal symptoms 2/24/2017rUse and misuse of cannabis and marihuana are frequent. About 5% of the adult population are current users but only 1.2% are dependent. The medical use of cannabis is controversial but there is some evidence for improvement of chronic pain and spasticity. The somatic toxicity of cannabis is well proven but limited and psychiatric disorders induced by cannabis are of more relevance, e.g. cognitive disorders, amotivational syndrome, psychoses and delusional disorders as well as physical and psychological dependence. The withdrawal symptoms are usually mild and do not require pharmacological interventions. To date there is no established pharmacotherapy for relapse prevention. Psychosocial interventions include psychoeducation, behavioral therapy and motivational enhancement. The CANDIS protocol is the best established German intervention among abstinence-oriented therapies121180+ field[22]: [Cannabis-induced disorders]. In German with English abstract RefMgr field[33]: Not in File B?t/Stassinos, G.L. Gonzales, L. Klein-Schwartz, W.2017VCharacterizing the toxicity and dose-effect profile of tramadol ingestions in childrenPediatric Emergency Care/online early: doi: 10.1097/PEC.0000000000001084not published, 01 Mar 17ACUTE Age analysis case central nervous system CHILDREN CLINICAL Confirmation DATA DEPRESSION dose Emergencies emergency EMERGENCY DEPARTMENT EVALUATION fatalities fatality HOME INFORMATION INGESTION IS Laboratories LABORATORY MANAGEMENT MET method methods NO outcome OVERDOSE PAEDIATRIC PATIENT pediatric Poison RESPIRATORY RESPIRATORY DEPRESSION seizure SEIZURES STUDY SYMPTOMS Toxicities TOXICITY TRAMADOL Vomiting 2/21/2017OBJECTIVES: Tramadol can cause life-threatening toxicity in overdose; however, data on its toxicity in children are lacking. This study investigates toxicity associated with tramadol ingestions in children. The hypothesis is that children will experience dose-related central nervous system and respiratory depression and seizures. METHODS: A retrospective evaluation of cases from the National Poison Center Data System between January 1, 2000, and December 31, 2013, was performed. Inclusion criteria were age below 6 years and single-substance acute tramadol ingestion. For dose-effect analysis, cases with sufficient dose quantity information were included. RESULTS: There were 7334 cases that met inclusion criteria. Outcomes were 84.8% no effect, 12.6% minor, 2.2% moderate, and 0.4% major effect. There was 1 fatality. Most of the children (36.4%) were treated/released from the emergency department; other management sites were home (36.4%), admission (5.9%), and others (3.2%). In the 1115 children with symptoms, drowsiness (N = 611) and vomiting (N = 178) occurred most frequently. More serious clinical effects included respiratory depression in 36 and seizures in 24 children. Of 2772 children with milligram dose recorded, there were 10 cases of respiratory depression and 6 of seizure. Median doses for respiratory depression and seizure were 225 (range, 50-600 mg) and 525 mg (range, 50-1050 mg), respectively. The minimum weight-based dose for respiratory depression/arrest was 7.9 mg/kg and for seizures, 4.8 mg/kg. CONCLUSIONS: Seizure and respiratory depression are uncommon in pediatric tramadol ingestions. Given the small number of patients with dose data and lack of laboratory confirmation of dose, more studies are needed to determine the minimum dose at which medical management is recommended121087. field[33]: Not in Files?u8Strojan, K. Lojk, J. Bregar, V.B. Veranic, P. Pavlin, M.2017`Glutathione reduces cytotoxicity of polyethyleneimine coated magnetic nanoparticles in CHO cells12-20Toxicology in Vitro41agent ANTIOXIDANT As CELL CYTOTOXICITY EXPOSURE formulation GLUTATHIONE GSH IS method NANOPARTICLES NO NPS OXIDATIVE STRESS Pathway Reduction SPONGE STRESS STUDY Synthesis use 2/16/2017Polyethyleneimine (PEI) is a polycationic compound frequently used as a transfection agent. However, cytotoxicity of PEI and PEI-coated nanoparticles (PEI NPs) is still a major obstacle in its use. In this study we report a method for reducing cytotoxicity of PEI NPs by addition of glutathione in NPs synthesis. Glutathione reduced cytotoxic effects for at least 30% and decreased observed oxidative stress response compared to standard formulation. Results showed that the effect was partially due to reduced zeta potential and partially due to protective antioxidant properties of glutathione. Addition of glutathione to cell culture media with concurrent exposure to PEI NPs proved to be insufficient for cytotoxicity reduction. Additionally, we compared internalization pathways of both PEI NPs and GSH NPs. NPs were only found in endosomes and no NPs were found free in the cytosol, as would be expected according to so called proton sponge hypothesis121123+ field[33]: Not in File B?v&Subritzky, T. Pettigrew, S. Lenton, S.2017QInto the void: regulating pesticide use in Colorado's commercial cannabis markets$International Journal of Drug Policy/online early: doi: 10.1016/j.drugpo.2017.01.014not published, 28 Feb 17As California Canada CANNABIS DATA FACILITIES GAP IS IV Knowledge method methods MODEL NO PAPER pesticide PESTICIDES policy PUBLIC PUBLICATION Regulation REGULATIONS Regulatory RESEARCH SAFETY standards Testing Toxicities TOXICITY US use2/4/2017dBACKGROUND: In 2014, Colorado implemented the world's first seed-to-sale recreational cannabis market under a commercial model. This paper aims to provide a thick descriptive account that gives insight into the issues and complexities of Colorado's pioneering and evolving attempt to regulate the use of pesticides on commercial cannabis plantations. METHODS: The paper examines multiple data sets including: (i) Colorado State Government documents; (ii) recreational cannabis regulations; (iii) mass and niche media publications (n=175); (iv) face-to-face interviews with key stakeholders, including seniors, regulators and industry executives (n=8); and (v) field notes from relevant conferences and cultivation facility tours in Denver in October, 2016. RESULTS: Two key issues are identified. First, a public safety threat has arisen relating to application of pesticides on cannabis with intensified toxicity in concentrated products of particular concern. Second, as a pioneering jurisdiction, Colorado faces a considerable knowledge gap. To expand collective learning on this issue, for which no regulatory template and little research exists, state regulators tapped industry and other stakeholder expertise while attempting to ensure public safety goals were achieved and regulatory capture by industry was limited. CONCLUSION: Four years since the recreational cannabis market in Colorado was legalised, the State continues to grapple with the pesticide issue as testing regulations and cultivation standards are yet to be finalised. While more work is needed, Colorado has made significant progress in developing regulations relating to this complex matter. As governments of countries such as Canada and US states, including California, contemplate changes to recreational cannabis laws, Colorado's experience can assist regulators in other jurisdictions considering policy change120888. field[33]: Not in File _B?wJSun, R. Zhang, J. Wei, H. Meng, X. Ding, Q. Sun, F. Cao, M. Yin, L. Pu, Y.2017hAcetyl-L-carnitine partially prevents benzene-induced hematotoxicity and oxidative stress in C3H/He mice)Environmental Toxicology and Pharmacology-online early: doi: 10.1016/j.etap.2017.02.013not published, 01 Mar 17Acetyl-l-carnitine ASSAY ATP BENZENE BLOOD Body Weight BONE BONE MARROW CELL Comet assay DNA DNA DAMAGE ENVIRONMENTAL EXPERIMENTAL EXPOSURE Frequency hematotoxicity HYDROGEN HYDROGEN PEROXIDE IS LEVELS MALE MDA MEMBRANE Metabonomics MICE Mitochondrial membrane potential mouse OCCUPATIONAL OIL OXIDATIVE STRESS OXYGEN Peroxide PLASMA Pollutant ROS SPECIES STRESS STUDY Toxicant Vehicle WEIGHT 2/13/2017aBenzene is an environmental pollutant and occupational toxicant which induces hematotoxicity. Our previous metabonomics study suggested that acetyl-l-carnitine (ALCAR) decreased in the mouse plasma and bone marrow (BM) cells due to benzene exposure. In the present study, the topic on whether ALCAR influences hematotoxicity caused by benzene exposure was explored. Thirty-two male C3H/He mice were divided into four groups: control group (C: vehicle, oil), benzene group (150mg/kg body weight (b.w.) benzene), benzene+A1 group (150mg/kg b.w. benzene+100mg/kg b.w. ALCAR), and benzene+A2 group (150mg/kg b.w. benzene+200mg/kg b.w. ALCAR). Benzene was injected subcutaneously, and ALCAR was orally administrated via gavage once daily for 4 weeks consecutively. After the experimental period, the blood routine, BM cell number and frequency of hematopoietic stem/progenitor cell (HS/PC) were assessed. The mitochondrial membrane potential and ATP level were determined to evaluate the mitochondrial function. Reactive oxygen species (ROS), hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels were also examined, and the comet assay was performed to measure oxidative stress. Results showed that ALCAR intervention can partially reduce the benzene-induced damage on BM and HS/PCs and can simultaneously alleviate the DNA damage by reducing benzene-induced H2O2, ROS, and MDA120993, field[33]: Not in File?x;Tang, G. Zhao, P. Gao, W. Cheng, M. Xin, J. Li, X. Wang, Y.2017BMortality and air pollution in Beijing: the long-term relationship238-243Atmospheric Environment150rAerosol AEROSOLS AIR AIR POLLUTION AMMONIA Beijing CALCIUM CARDIOVASCULAR Cerebrovascular disease chemical China CONCENTRATIONS DATA DISEASE EPIDEMIOLOGY EXPOSURE FORMALDEHYDE HEALTH HUMAN Human health LEAD Long term Long-term MALIGNANT MORTALITY NITRATE outcome Pollutant POLLUTION RESPIRATORY RESPIRATORY DISEASE Respiratory diseases STUDY SULPHATE trends TUMOUR USAGE20171Since the 1980s, air pollution has become a major problem in northern China. Exposure to the extremely high concentrations of aerosols and trace gases might lead to important human health outcomes, including respiratory, cardiovascular and cerebrovascular diseases and malignant tumours. In this study, we collected data on mortality, visibility and the concentrations of certain air pollutants in Beijing from 1949 to 2011. Our goal was to investigate the mortality trends of different types of diseases and the relationship between mortality and air pollution. Based on the chemical compositions in particles and satellite formaldehyde, we found that mortality due to circulatory diseases was correlated with sulphate, nitrate and formaldehyde, whereas respiratory diseases were correlated with calcium, sulphate and nitrate, and malignant tumours was correlated with ammonium, nitrate and formaldehyde with an 11-year lag. The different responses to different air pollutants for different diseases are primarily a result of energy usage. Copyright © 2016 Elsevier Ltd1206980 field[33]: Not in FileB?ymTapia-Orozco, N. Santiago-Toledo, G. Barron, V. Espinosa-Garcia, A.M. Garcia-Garcia, J.A. Garcia-Arrazola, R.2017Environmental epigenomics: Current approaches to assess epigenetic effects of endocrine disrupting compounds (EDC's) on human health)Environmental Toxicology and Pharmacology-online early: doi: 10.1016/j.etap.2017.02.004not published, 01 Mar 17banalysis ANALYTICAL As ASSESSMENT CELL chemical CHEMICALS CONTAINERS DETECTION DNA DNA methylation DRUG drugs ENDOCRINE Endocrine disrupting compounds Endocrine disruptor endocrine disruptors ENVIRONMENTAL evidence EXPOSURE FOOD HEALTH HUMAN Human health Humans Incidence IS LEAD method personal care products prevalence REVIEW STUDY TECHNIQUE TOXICOLOGY 2/10/2017Environmental Epigenomics is a developing field to study the epigenetic effect on human health from exposure to environmental factors. Endocrine disrupting chemicals have been detected primarily in pharmaceutical drugs, personal care products, food additives, and food containers. Exposure to endocrine-disrupting chemicals (EDCs) has been associated with a high incidence and prevalence of many endocrine-related disorders in humans. Nevertheless, further evidence is needed to establish a correlation between exposure to EDC and human disorders. Conventional detection of EDCs is based on chemical structure and concentration sample analysis. However, substantial evidence has emerged, suggesting that cell exposure to EDCs leads to epigenetic changes, independently of its chemical structure with non-monotonic low-dose responses. Consequently, a paradigm shift in toxicology assessment of EDCs is proposed based on a comprehensive review of analytical techniques used to evaluate the epigenetic effects. Fundamental insights reported elsewhere are compared in order to establish DNA methylation analysis as a viable method for assessing endocrine disruptors beyond the conventional study approach of chemical structure and concentration analysis120994, field[33]: Not in File?zETbler, S.M. Wilkerson, M.A. Porter, W.H. Smith, A.J. Chandler, M.H.H.1990LSevere phenytoin intoxication as a result of altered protein binding in aids698-700Annals of Pharmacotherapy247-8agent AIDS As ASSAY case CONCENTRATIONS DRUG INTOXICATION IS PATIENT PHENYTOIN PLASMA PROTEIN Protein Binding PUBLICATION RENAL RISK SERUM Syndrome toxic Toxicities TOXICITY1990Alterations in plasma protein binding may alter patient response to pharmaceutical agents because only free drug is considered to be pharmacologically active. Such alterations appear to be more significant with highly bound agents such as phenytoin. Traditionally, most drug assays monitor total drug concentrations and do not quantitate free drug. When binding alterations are present, total drug concentrations may mislead clinicians in evaluating patient response. We describe a case in which profound hypoalbuminemia (0.2 g/dL), associated with focal segmental glomerulosclerosis, produced toxic free phenytoin concentrations (4.9 mug/mL) in an HIV-positive 25-year-old black woman. At such a high serum concentration of free phenytoin, the patient exhibited seizure-like effects. Renal abnormalities and hypoalbuminemia associated with acquired immunodeficiency syndrome (AIDS) may place patients at risk for elevated free fractions of phenytoin and subsequent toxicity. Copyright © 1990, © 1990 SAGE Publications120820, field[33]: Not in File?{TTelles-Correia, D. Barbosa, A. Cortez-Pinto, H. Campos, C. Rocha, N.B.F. Machado, S.2017^Psychotropic drugs and liver disease: a critical review of pharmacokinetics and liver toxicity26-38?World Journal of Gastrointestinal Pharmacology and Therapeutics81sagent author critical review DISEASE DRUG drug induced liver injury drug-induced Drug-induced liver injury drugs evidence HEPATIC HEPATOTOXICITY IMPAIRMENT injuries Injury IS LIVER LIVER DISEASE liver injury METABOLISM MONITORING PATIENT pharmacokinetic PHARMACOKINETICS prevalence PROTEIN PSYCHIATRIC PSYCHOTROPIC DRUGS REACTIONS REVIEW RISK SEVERITY Toxicities TOXICITY2/6/2017The liver is the organ by which the majority of substances are metabolized, including psychotropic drugs. There are several pharmacokinetic changes in end-stage liver disease that can interfere with the metabolization of psychotropic drugs. This fact is particularly true in drugs with extensive first-pass metabolism, highly protein bound drugs and drugs depending on phase I hepatic metabolic reactions. Psychopharmacological agents are also associated with a risk of hepatotoxicity. The evidence is insufficient for definite conclusions regarding the prevalence and severity of psychiatric drug-induced liver injury. High-risk psychotropics are not advised when there is pre-existing liver disease, and after starting a psychotropic agent in a patient with hepatic impairment, frequent liver function/lesion monitoring is advised. The authors carefully review the pharmacokinetic disturbances induced by end-stage liver disease and the potential of psychopharmacological agents for liver toxicity121144+ field[33]: Not in File DB?|>Thetkathuek, A. Yenjai, P. Jaidee, W. Jaidee, P. Sriprapat, P.2017PPesticide exposure and cholinesterase levels in migrant farm workers in ThailandJournal of Agromedicine0online early: doi: 10.1080/1059924X.2017.1283276not published, 20 Feb 17XACUTE Age analysis Cambodia chemical CHOLINESTERASE CHRONIC DATA EXPOSURE Frequency Gender HEALTH ILLNESS INDUSTRIAL Inhibition INSECTICIDE LEVELS low-level MALE Measurement method MODEL OCCUPATIONAL Odds Ratio pesticide PESTICIDES POISONING QUESTIONNAIRE Regression Analysis RISK SCREENING SERUM STUDY SURVEY Thailand use WHO workers workplace 1/31/2017In this study we examined the effects of pesticides in migrant farm workers from Cambodia after workplace exposure on fruit plantations in eastern Thailand. We studied 891 migrant farm workers employed on pineapple, durian, and rambutan plantations in Thailand. Data were collected via a detailed questionnaire survey and measurements of serum cholinesterase level (SChE). The majority of subjects was male (57.7%), with an average age of 30.3 years. Most subjects (76.8%) were moderately aware of good industrial hygiene practices. SChE level was divided into 4 groups based on the results. Only 4.4% had normal levels of cholinesterase activity, 20.5% had slightly reduced levels, 58.5% had markedly reduced levels and were "at risk," and 16.6% who had highest levels of cholinesterase inhibition were deemed to be in an "unsafe" range. SChE was classified into 2 groups, SChE value of 87.5 was "normal" and < 87.5 units/ml "abnormal." For the multiple logistic regression analysis of the abnormal SChE levels, the variables entered in the model included gender, period of insecticide use, the total area of plantation, frequency of spraying, period of daily insecticide spraying, and insecticide spraying method. The results indicated that the aOR (adjust odds ratio) for male migrant farm workers (95% CI) was 1.58 (1.14, 2.17). The OR for farm migrant workers who worked on larger plantations of more than 39.5 acres (95% CI) was 2.69 (1.51, 4.82). Finally, the OR for the migrant farm workers who used a backpack sprayer (95% CI) was 2.07(1.28, 3.34). These results suggest that health screening should be provided to migrant farm workers, especially those who spray pesticides on plantations of > 39 acres, who use a backpack sprayer, or have a low level of compliance with accepted industrial hygiene practices. These three classes of workers are at increased risk of chemical exposures and developing acute or chronic illness from pesticide exposures120771/ field[33]: Not in File?}fThiel, C. Cordes, H. Fabbri, L. Aschmann, H.E. Baier, V. Smit, I. Atkinson, F. Blank, L.M. Kuepfer, L.2017WA comparative analysis of drug-induced hepatotoxicity in clinically relevant situationse1005280PLoS Computational Biology132Adverse adverse drug event adverse event Adverse events analysis Biomarker BIOMARKERS CLINICAL COMPARATIVE DATA DIAGNOSIS dose DRUG drug effects drug-drug interactions drug-induced drugs Hepatotoxic HEPATOTOXICITY IDENTIFICATION IN VITRO INTERACTION IS MECHANISM Mechanisms PATIENT pharmacokinetic Pharmacokinetic modeling REACTIONS THERAPEUTIC toxic Toxic reaction Toxicities TOXICITY use2/2017Drug-induced toxicity is a significant problem in clinical care. A key problem here is a general understanding of the molecular mechanisms accompanying the transition from desired drug effects to adverse events following administration of either therapeutic or toxic doses, in particular within a patient context. Here, a comparative toxicity analysis was performed for fifteen hepatotoxic drugs by evaluating toxic changes reflecting the transition from therapeutic drug responses to toxic reactions at the cellular level. By use of physiologically-based pharmacokinetic modeling, in vitro toxicity data were first contextualized to quantitatively describe time-resolved drug responses within a patient context. Comparatively studying toxic changes across the considered hepatotoxicants allowed the identification of subsets of drugs sharing similar perturbations on key cellular processes, functional classes of genes, and individual genes. The identified subsets of drugs were next analyzed with regard to drug-related characteristics and their physicochemical properties. Toxic changes were finally evaluated to predict both molecular biomarkers and potential drug-drug interactions. The results may facilitate the early diagnosis of adverse drug events in clinical application120805. field[33]: Not in File B?~,Thirakul, P. Hair, S. Bergen, L. Pearson, M.2017dClinical presentation, autopsy results and toxicology findings in an acute N-ethylpentylone fatality Journal of Analytical Toxicology%online early: doi: 10.1093/jat/bkx004not published, 20 Feb 17iACUTE analysis arm ARREST AUTOPSY Behavior BICARBONATE BLOOD CARDIAC CARDIAC ARREST CATHINONE Cathinones CHROMATOGRAPHY CLINICAL Clinical presentation COAGULATION DEATH designer drug DESIGNER DRUGS DRUG drugs Ethylpentylone FAILURE fatalities fatality GA GAS GAS CHROMATOGRAPHY HEART HEPATIC HI HOSPITAL hypoglycemia injuries Injury INTENSIVE CARE intensive care unit INTOXICATION INTRAVENOUS Laboratories LABORATORY MALE N-Ethylpentylone NOVEL PSYCHOACTIVE SUBSTANCES pH RENAL RESPIRATORY RESPIRATORY FAILURE RHABDOMYOLYSIS synthetic cathinone Synthetic cathinones TEMPERATURE TOXICOLOGY TREATMENT TROPONINS UNIT WHO 1/30/2017The clinical presentation, autopsy findings and toxicology results in an acute fatality involving N-ethylpentylone, a new cathinone derivative, are described. Law enforcement transported a male who was agitated and exhibiting unusual behavior to a local hospital. Upon arrival at the hospital, his body temperature was 105.5 degrees Fahrenheit and his blood pH was 6.7. Clinical laboratory analysis revealed elevated troponins, rhabdomyolysis, hypoglycemia, hepatic and renal injury, respiratory failure and disseminated intravascular coagulation. He was intubated and admitted to the intensive care unit, treated with cooling blankets, bicarbonate and intravenous fluids. Despite medical treatment, he went into cardiac arrest and was pronounced dead ~36 h after admission. Autopsy findings identified some abrasions on his arms and legs, a bloody nose and a mildly enlarged heart. Antemortem blood was analyzed by gas chromatography coupled with a mass spectrometer which identified N-ethylpentylone. Based on clinical presentation, autopsy findings and toxicology results, the medical examiner concluded the cause of death was intoxication by N-ethylpentylone and the manner of death was accident120773$ field[33]: Not in File B?1Thornton, J.D. Lyvers, E. Scott, V.G. Dwibedi, N.2017SPharmacists' readiness to provide naloxone in community pharmacies in West Virginia/Journal of the American Pharmacists Association-online early: doi: 10.1016/j.japh.2016.12.070not published, 28 Feb 17;Adverse adverse event Adverse events Affect Age As Benefits BUPRENORPHINE DATA DATA COLLECTION dispensing DRUG drugs EDUCATION EFFICACY EPIDEMIC HEALTH IS MALE MODEL NALOXONE OPIOID opioid dependence opioid use disorder Opioids outcome over the counter PATIENT SCALE SEVERITY STUDY SURVEY susceptibility THERAPY use2/2/2017OBJECTIVES: The objective of this study is to assess West Virginia pharmacists' stocking and dispensing practices of opioid-related medications and to identify the educational needs relating to providing naloxone in community pharmacies. DESIGN: A cross-sectional, anonymous, 49-item survey was created and validated to assess the educational needs of West Virginia community pharmacists. SETTING: West Virginia. PARTICIPANTS: The data collection instrument was administered to 266 pharmacists currently licensed in West Virginia at 6 continuing pharmacy education events throughout the state from March 1 to June 15, 2016. OUTCOME MEASURES: Pharmacists' educational needs were determined using the Extended Parallel Process Model, which has 4 main constructs: perceived severity, perceived susceptibility, response efficacy, and self-efficacy. Pharmacists' stocking and dispensing of opioids and related medications were also assessed. RESULTS: Pharmacists completed 157 surveys. They were mostly male (56.1%), full-time employees (67.5%), worked mostly in community pharmacies (69.4%), and had a mean age of 50.19 years (SD = 13.62). The newly adapted opioid perceived efficacy and perceived severity of opioid adverse events scales were tested for reliability and validity. Only 20.4% of the community pharmacists surveyed felt comfortable selling naloxone without a prescription. As for the other opioid-related medications, only 53.3% stocked buprenorphine and 74.8% stocked buprenorphine/naloxone. CONCLUSIONS: As the most accessible health care providers, community pharmacists are acutely aware of how the opioid epidemic affects their communities. Some pharmacists in West Virginia are hesitant to stock and dispense opioids and opioid-dependence medications. Although this may decrease the flow of potentially abused drugs into the community, it may also restrict access to necessary therapy for patients with opioid use disorder. Furthermore, pharmacists in West Virginia are not yet comfortable stocking and dispensing naloxone. Tailored educational materials can help in controlling the pharmacists' fear and reinforce the benefits of over-the-counter naloxone use120894, field[33]: Not in File?MThors, L. Lindberg, S. Johansson, S. Koch, B. Koch, M. Hagglund, L. Bucht, A.2017GRSDL decontamination of human skin contaminated with the nerve agent VX47-54Toxicology Letters269ZACETONITRILE ACUTE acute poisoning agent analysis ANIMAL Animals As BLOOD CELL chemical chemical warfare CIRCULATION CONCENTRATIONS DATA DECONTAMINATION DERMAL Dermal exposure EFFICACY EVALUATION EXPOSURE flow-through diffusion cell HUMAN impact IN VITRO IS LEAD MECHANISM MEMBRANE NERVE NERVE AGENT nerve agents NMR NMR SPECTROSCOPY ORGANIC ORGANIC SOLVENT organophosphorus organophosphorus compound ORGANOPHOSPHORUS COMPOUNDS PENETRATION pesticide PESTICIDES pH POISONING REACTIONS REMOVAL RSDL SKIN solubility SOLVENT STUDY SYSTEMIC toxic toxic effects Toxicities TOXICITY TREATMENT VX Warfare WATER2/5/2017 Dermal exposure to low volatile organophosphorus compounds (OPC) may lead to penetration through the skin and uptake in the blood circulation. Skin decontamination of toxic OPCs, such as pesticides and chemical warfare nerve agents, might therefore be crucial for mitigating the systemic toxicity following dermal exposure. Reactive skin decontamination lotion (RSDL) has been shown to reduce toxic effects in animals dermally exposed to the nerve agent VX. In the present study, an in vitro flow-through diffusion cell was utilized to evaluate the efficacy of RSDL for decontamination of VX exposed to human epidermis. In particular, the impact of timing in the initiation of decontamination and agent dilution in water was studied. The impact of the lipophilic properties of VX in the RSDL decontamination was additionally addressed by comparing chemical degradation in RSDL and decontamination efficacy between the VX and the hydrophilic OPC triethyl phosphonoacetate (TEPA). The epidermal membrane was exposed to 20, 75 or 90% OPC diluted in deionized water and the decontamination was initiated 5, 10, 30, 60 or 120minutes post-exposure. Early decontamination of VX with RSDL, initiated 5-10minutes after skin exposure, was very effective. Delayed decontamination initiated 30-60minutes post-exposure was less effective but still the amount of penetrated agent was significantly reduced, while further delayed start of decontamination to 120minutes resulted in very low efficacy. Comparing RSDL decontamination of VX with that of TEPA showed that the decontamination efficacy at high agent concentrations was higher for VX. The degradation mechanism of VX and TEPA during decontamination was dissected by 31P NMR spectroscopy of the OPCs following reactions with RSDL and its three nucleophile components. The degradation rate was clearly associated with the high pH of the specific solution investigated; i.e. increased pH resulted in a more rapid degradation. In addition, the solubility of the OPC in RSDL also influenced the degradation rate since the degradation of VX was significantly faster when the NMR analysis was performed in the organic solvent acetonitrile compared to water. In conclusion, we have applied the in vitro flow-through diffusion cell for evaluation of skin decontamination procedures of human epidermis exposed to OPCs. It was demonstrated that early decontamination is crucial for efficient mitigation of epidermal penetration of VX and that almost complete removal of the nerve agent from the skin surface is possible. Our data also indicate that the pH of RSDL together with the solubility of OPC in RSDL are of primary importance for the decontamination efficacy120924. field[33]: Not in File1?7Tincu, R.C. Cobilinschi, C. Ghiorghiu, Z. Macovei, R.A.2016.Acute mercury poisoning from occult ritual use73-762Romanian Journal of Anaesthesia and Intensive Care231jACTIVATED CHARCOAL ACUTE As case CASE REPORT Case-report cathartic CATHARTICS Charcoal COSMETIC DECONTAMINATION Emissions ENVIRONMENTAL ENVIRONMENTAL ISSUE EXPOSURE FEMALE GASTRIC GASTRIC LAVAGE GASTROINTESTINAL GASTROINTESTINAL DECONTAMINATION HOSPITAL INDUSTRIAL ingested INGESTION IS LAVAGE Liquids MERCURY Nausea ORAL outcome PATIENT POISONING Source use WHO2016Mercury exposure is a serious environmental issue that concerns people worldwide. Industrial emissions containing mercury, some pharmaceutical and cosmetic products represent exposure sources. In Romania, as in many other countries, a supplementary cause for mercury exposure is represented by various occult rituals where liquids containing mercury are supposed to be ingested. We present the case of a 28 year old female who was admitted to the hospital for oral paresthesia, nausea, vertigo and sialorrhoea, after ingesting 100 ml diluted liquid mercury during an occult ritual. After the gastrointestinal decontamination, including gastric lavage, activated charcoal and cathartics, the outcome was favourable and 48 hours after admission the patient was discharged. This case report emphasizes the importance of an early digestive decontamination in mercury poisoning and the danger of mercury ingestion during various occult rituals. Copyright © 2016, Editura Clasium. All rights reserved120810- field[33]: Not in File B?fTittarelli, R. Pichini, S. Pedersen, D.S. Pacifici, R. Moresco, M. Pizza, F. Busardò, F.P. Plazzi, G.2017Ultra-high-performance liquid chromatography tandem mass spectrometry determination of GHB, GHB-glucuronide in plasma and cerebrospinal fluid of narcoleptic patients under sodium oxybate treatmentForensic Science International2online early: doi: 10.1016/j.forsciint.2017.01.015not published, 20 Feb 17ACID ANALYTICAL BLOOD Blood samples CEREBROSPINAL FLUID CHROMATOGRAPHY CONCENTRATIONS determination dose DOSE-RESPONSE DRUG FORENSIC Frequency GAMMA HYDROXYBUTYRIC ACID GHB HYDROXYBUTYRIC ACID IS Liquid chromatography Liquid chromatography tandem mass spectrometry MASS SPECTROMETRY Measurement method MONITORING NARCOLEPSY NO OREXIN PATIENT pharmacokinetic PHARMACOKINETICS PLASMA Plasma pharmacokinetics SALT SODIUM SODIUM OXYBATE SPECTROMETRY STUDY SYMPTOMS Tandem Mass Spectrometry THERAPEUTIC Therapeutic drug monitoring Time TREATMENT 1/25/2017Sodium oxybate (Xyrem(R)), the sodium salt of gamma- hydroxybutyric acid (GHB), is a first-line treatment of the symptoms induced by type 1 narcolepsy (NT1) and it is highly effective in improving sleep architecture, decreasing excessive daytime sleepiness and the frequency of cataplexy attacks. Using an ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) validated method, GHB was determined together with its glucuronide (GHB-gluc), in plasma and cerebrospinal fluid (CSF) samples of NT1 patients under sodium oxybate treatment. To characterize the plasma pharmacokinetics of GHB, three subjects with NT1 were administered at time 0 and 4h with 1.25, 1.5 and 3.55g Xyrem(R), respectively and had their blood samples collected at 7 time points throughout an 8-h session. CSF specimens, collected for orexin A measurement from the same three subjects 6h after their second administration, were also tested. The results obtained suggested that GHB plasma values increased disproportionally with the rising doses, (Cmax0-4: 12.53, 32.95 and 69.62mug/mL; Cmax4-8: 44.93, 75.03 and 111.93mug/mL for total Xyrem(R) dose of 2.5, 3 and 7g respectively) indicating non-linear dose-response. GHB-Gluc was present only in traces in all plasma samples from treated patients, not changing with increasing Xyrem(R) doses. GHB values of 5.62, 6.10 and 17.74mug/mL for 2, 3 and 7g Xyrem(R) were found in CSF with a significant difference from control values. GHB-Gluc was found in negligible concentrations with no differences to those of control individuals. In conclusion this simple and fast UHPLC-MS/MS method proved useful for pharmacokinetic studies and therapeutic drug monitoring of GHB in narcoleptic patients treated with sodium oxybate1207671 field[33]: Not in File B??Tomasi, S. Roberts, K.J. Stull, J. Spiller, H.A. McKenzie, L.B.20171Pediatric exposures to veterinary pharmaceuticals Pediatrics)online early: doi: 10.1542/peds.2016-1496not published, 28 Feb 17RAge agent analysis ANIMAL ANTIMICROBIAL Attention Awareness Behavior case CHILDREN dispensing DRUG drugs EPIDEMIOLOGY EXPOSURE FACILITIES HEALTH Health effects HOME HUMAN INGESTION Long term Long-term method methods outcome PAEDIATRIC pediatric Pharmaceuticals Poison PUBLIC RISK Route SPECIES STATISTICS use Veterinary VETERINARY PRODUCT2/6/2017OBJECTIVE: To describe the epidemiology of veterinary pharmaceutical-related exposures to children based on calls to a regional poison control center. METHODS: A retrospective analysis of pediatric (vTomassoni, A.J. Hawk, K.F. Jubanyik, K. Nogee, D.P. Durant, T. Lynch, K.L. Patel, R. Dinh, D. Ulrich, A. D'Onofrio, G.2017CMultiple fentanyl overdoses - New Haven, Connecticut, June 23, 2016107-111,MMWR - Morbidity and Mortality Weekly Report664ANTIDOTE As case COCAINE COMMUNICATION DISTRIBUTION dose DRUG Emergencies emergency EMERGENCY DEPARTMENT Emergency Medical Services ENDOTRACHEAL INTUBATION FAILURE family FENTANYL harm HEALTH HEROIN HOSPITAL ICU INFUSION INTENSIVE CARE intensive care unit INTOXICATION INTUBATION NALOXONE OPIOID Opioid overdose OVERDOSE PATIENT PUBLIC PUBLIC HEALTH RESPIRATORY RESPIRATORY FAILURE Route SERVICE Signs and symptoms Source SYMPTOMS Time UNIT use WHO2/3/2017VOn the evening of June 23, 2016, a white powder advertised as cocaine was purchased off the streets from multiple sources and used by an unknown number of persons in New Haven, Connecticut. During a period of less than 8 hours, 12 patients were brought to the emergency department (ED) at Yale New Haven Hospital, experiencing signs and symptoms consistent with opioid overdose. The route of intoxication was not known, but presumed to be insufflation ("snorting") in most cases. Some patients required doses of the opioid antidote naloxone exceeding 4 mg (usual initial dose = 0.1-0.2 mg intravenously), and several patients who were alert after receiving naloxone subsequently developed respiratory failure. Nine patients were admitted to the hospital, including four to the intensive care unit (ICU); three required endotracheal intubation, and one required continuous naloxone infusion. Three patients died. The white powder was determined to be fentanyl, a drug 50 times more potent than heroin, and it included trace amounts of cocaine. The episode triggered rapid notification of public health and law enforcement agencies, interviews of patients and their family members to trace and limit further use or distribution of the fentanyl, immediate naloxone resupply and augmentation for emergency medical services (EMS) crews, public health alerts, and plans to accelerate naloxone distribution to opioid users and their friends and families. Effective communication and timely, coordinated, collaborative actions of community partners reduced the harm caused by this event and prevented potential subsequent episodes120797# field[33]: Not in File ?7Toschi, N. Ciulli, S. Diciotti, S. Duggento, A. Guerrisi, M. Magrini, A. Campagnolo, L. Pietroiusti, A. Toschi, N. Ciulli, S. Diciotti, S. Duggento, A. Guerrisi, M. Magrini, A. Campagnolo, L. Pietroiusti, A. Guerrisi, M. Ciulli, S. Campagnolo, L. Diciotti, S. Magrini, A. Pietroiusti, A. Duggento, A. Toschi, N.2016WForecasting nanoparticle toxicity using nonlinear predictive regressor learning systems137-140Conf Proc IEEE Eng Med Biol Soc2016ADENOSINE As ASSAY biological CELL COST CYTOTOXICITY DATABASE EVALUATION IS method methods mining NANOPARTICLES PROTOCOL TISSUE Toxicities TOXICITY trends Validation8/2016Nanoparticle (NP) toxicity is determined by a vast number of topological, sterical, physico-chemical as well as biological properties, rendering a priori evaluation of the effect of NP on biological tissue as arduous as it is necessary and urgent. We aimed at mining the HORIZON 2020 MODENA COST NP cytotoxicity database through nonlinear predictive regressor learning systems in order to assess the power of available NP descriptors and assay characteristics in predicting NP toxicity. Specifically, we assessed the results of cytotoxicity assays performed on 57 NP and trained two different nonlinear regressors (Support Vector Regressors [SVR] with polynomical kernels and Radial Basis Function [RBF] regressors) within a nested-cross validation scheme for parameter optimization to predict toxicity as quantified by EC25, EC50 and slope while using the regressional ReliefF algorithm (RReliefF) for feature selection. Available NP attributes were material, coating, cell type, dispersion protocol, shape, 1st and 2nd dimension, aspect ratio, surface area, zeta potential and size in situ. In most regressor learning systems, after feature selection with the RReliefF algorithm, the correlation between real and estimated toxicity endpoint values increased monotonically with the number of included features, reaching values above 0.90. The best performance was obtained with RBF regressors, and the most informative features in predicting toxicity endpoints were related to nanoparticle structure. These trends did not change significantly between toxicity endpoints. In conclusion, EC25, EC50 and slope can be predicted with high correlation using purely data-driven, machine learning methods in Adenosine triphosphate (ATP)-based NP cytotoxicity assays120973+ field[33]: Not in FileW?$Tramer, F. Da Ros, T. Passamonti, S.20122Screening of fullerene toxicity by hemolysis assay203-217#Nanotoxicity: methods and protocols Reineke, J. Humana Press926 As ASSAY biological BLOOD carbon CELL Characterization chemical CYTOTOXICITY EXPERIMENTAL FULLERENES hemoglobin hemolysis HUMAN INJECTION INTRAVENOUS INTRAVENOUS INJECTION IS MEMBRANE MODEL PLASMA Release Route SCREENING solubility TEST toxic Toxicities TOXICITY use20120Fullerene is a compound formed during carbon burst that has been produced synthetically starting from the 1990s. The spherical shape and the characteristic carbon bonds of this allotrope (C60) have made it a suitable molecule for many applications. During the last decade, the low aqueous solubility of this molecule has been improved by chemical functionalization allowing the use of fullerene derivatives in biological fluids. The characterization of the toxicity potential of fullerenes is therefore of growing interest for any biomedical application. Intravenous injection is one of the possible routes of their administrations and therefore red blood cells are among the first targets of fullerene cytotoxicity. Human red blood cells are easily available and separated from plasma. Membrane disruption by toxic compounds is easily detected in red blood cells as release of hemoglobin in the cell medium, which can be assayed spectrophotometrically at lambda = 415 nm. Due to the high molar extinction coefficient of hemoglobin, the assay can be performed on a small amount of both red blood cells and the test compounds, which might be available only in small quantities. So, the hemolysis assay is a simple screening test, whose results can guide further investigations on cytotoxicity in more complex experimental models.120833. in Molecular BiologyRRefMgr field[33]: Not in File?J%Trangadia, M. Kharadi, R. Gupta, B.D.2016Epidemiologic study of fatal and non-fatal poisoning case in pediatric, around Jamnagar Region, Gujarat in India (January-December 2013)128-134AInternational Journal of Medical Toxicology and Forensic Medicine63ACCIDENTAL Age agent ANIMAL As Awareness case chemical CHEMICALS childhood CHILDREN College epidemiologic EPIDEMIOLOGY FATAL FEMALE FORENSIC Forensic Medicine HOME homicidal HOSPITAL Incidence India INDIUM KEROSENE MALE Medicine method methods MORBIDITY MORTALITY NO Observation ORAL P PAEDIATRIC pediatric POISONING Population prevalence Retrospective study Route SAFETY STING STUDY suicidal TOXICOLOGY2016bBackground: In spite of successful interventions and safety measures to prevent accidental poisoning in pediatric population, it contributes significantly to childhood morbidity and mortality. Methods: This Retrospective study comprising of 204 cases of poisoning was conducted during the period of a year, from 1st January 2013- 31st Dec 2013 at Forensic Medicine Department, Shri M. P. Shah Govt. College, Guru Gobindsinh Govt. hospital (GGG) Jamnagar. Results: The incidence of poisoning was more in age group of 2-3 year. Majority of victims were male as compared to females. The most common place of incidence of poisoning was home followed by playground. Most common route of poisoning was oral followed by poisonous animal bites and sting. All poisoning cases were accidental in nature. No suicidal or homicidal case was found in our study. Poisoning cases were more common in the months of April and October than in the rest of the months. The most common agent involved in pediatric poisoning was kerosene. Conclusion: Based on observation most of the cases were accidental poisoning in young children so precaution like proper storage and proper disposal of chemicals and parental awareness regarding these issues could sufficiently reduce the prevalence of poisoning among children. Copyright © 2016 Forensic Medicine and Toxicology Department. All rights reserved120829E Not in File H?J'Trotter Davis, M. Bateman, B. Avorn, J.2017KEducational outreach to opioid prescribers: the case for academic detailing S147-S151Pain Physician202SABUSE ADDICTION As ASSESSMENT ATRIAL FIBRILLATION case CHRONIC CLINICAL DEATH Deaths DISEASE DRUG EPIDEMIC EVIDENCE-BASED HEALTH HOSPITAL INFORMATION IS limits MANAGEMENT method methods MISUSE MONITORING Obstructive OPIOID Opioid abuse Opioids OVERDOSE pain PATIENT policy PRESCRIBING prescription drug monitoring PUBLIC PUBLIC HEALTH PULMONARY Regulation REGULATIONS TREATMENT use WHO2/2017UNonmedical use of opioid medications constitutes a serious health threat as the rates of addiction, overdoses, and deaths have risen in recent years. Increasingly, inappropriate and excessively liberal prescribing of opioids by physicians is understood to be a central part of the crisis. Public health officials, hospital systems, and legislators are developing programs and regulations to address the problem in sustained and systematic ways that both insures effective treatment of pain and appropriate limits on the availability of opioids. Three approaches have obtained prominence as means of avoiding excessive and inappropriate prescribing, including: providing financial incentives to physicians to change their clinical decision through pay-for-performance contracts, monitoring patient medications through Prescription Drug Monitoring Programs, and educational outreach to physicians. A promising approach to educational outreach to physicians is an intervention known as "academic detailing." It was developed in the 1980s to provide one-on-one educational outreach to physicians using similar methods as the pharmaceutical industry that sends "detailers" to market their products to physician practices. Core to academic detailing, however, is the idea that medical decisions should be based on evidence-based information, including managing conditions with updated assessment measures, behavioral, and nonpharmacological interventions. With the pharmaceutical industry spending billions of dollars to advertise their products, individual practitioners can have difficulty gathering unbiased information, especially as the number of approved medications grows each year. Academic detailing has successfully affected the management of health conditions, such as atrial fibrillation, chronic obstructive pulmonary disease, and recently, has targeted physicians who prescribe opioids. This article discusses the approach as a potentially effective preventative intervention to address the epidemic of opioid overuse.Key words: Opioid abuse, opioid misuse, academic detailing, health policy, interactive education,prevention121083K Not in Fileq?MTsai, P.H. Chou, M.C. Chiang, S.W. Chung, H.W. Liu, H.S. Kao, H.W. Chen, C.Y.2017Early white matter injuries in patients with acute carbon monoxide intoxication: a tract-specific diffusion kurtosis imaging study and STROBE compliant articlee5982Medicine (Baltimore)965ACUTE Age As carbon CARBON MONOXIDE CO COMPARISON DATA DETECTION Diffusion tensor imaging EVALUATION healthy volunteers Imaging injuries Injury INTOXICATION MAGNETIC RESONANCE NEUROLOGICAL NEUROTOXICITY PATIENT POISONING STUDY THERAPEUTIC VOLUNTEER2/2017"Evaluation of acute white matter injuries caused by carbon monoxide (CO) poisoning can be limited by conventional magnetic resonance (MR) imaging. We aim to evaluate the feasibility of diffusion kurtosis imaging (DKI) for early detection of white matter alterations in patients with acute CO intoxication.A total of 30 subjects including 15 acute CO patients and 15 age- and sex-matched healthy volunteers were enrolled in this study. MR examinations were performed on a 3T MR scanner within 8 days after CO intoxication. DKI data were acquired to derive axial, radial, and mean kurtosis, as well as fractional anisotropy (FA), axial, radial, and mean diffusivity for tract-specific comparisons between the 2 groups.Significant decreases of mean kurtosis were shown in the genu of corpus callosum, cingulum, and motor-related tracts (corticospinal and corticobulbar tracts) in patients with acute CO intoxication as compared with controls. On the contrary, significant differences of FA values were merely shown in the regions of corticospinal tracts.DKI demonstrated comparably stronger potential than diffusion tensor imaging in terms of early detection of white matter changes in patients with acute CO intoxication. This may have implications in therapeutic strategy for managing acute CO intoxication patients120796- field[33]: Not in File HB?GTylleskar, I. Skulberg, A.K. Nilsen, T. Skarra, S. Jansook, P. Dale, O.20178Pharmacokinetics of a new, nasal formulation of naloxone)European Journal of Clinical Pharmacology,online early: doi: 10.1007/s00228-016-2191-1not published, 16 Feb 17As BIOAVAILABILITY CONCENTRATIONS dose Emergencies emergency epidemiologic formulation HUMAN INTRAVENOUS IS IV KINETICS LEVELS Liquid chromatography tandem mass spectrometry Liquid chromatography-tandem mass spectrometry MASS SPECTROMETRY method methods NALOXONE NASAL OPIOID Opioid overdose OVERDOSE pharmacokinetic PHARMACOKINETICS quantification SERUM SPECTROMETRY STUDY SYSTEMIC t THERAPEUTIC Time TRIAL use VOLUNTEER 1/31/2017hPURPOSE: Nasal naloxone is wanted for bystander administration in opioid overdose and as a needle-free alternative for emergency medical personnel. Epidemiologic studies have indicated a therapeutic effect of bystander administration of low-concentration/high-volume formulations. The objective for this study was to describe the nasal pharmacokinetics of a new high-concentration/low-volume nasal formulation of naloxone. METHODS: This was an open, randomized triple crossover trial in healthy, human volunteers (n = 12) where two doses of nasal naloxone (0.8 and 1.6 mg) and one intravenous dose (1.0 mg) were compared. Fifteen serum samples were collected before and until 6 h after naloxone administration. Quantification of naloxone was performed by a validated liquid chromatography-tandem mass spectrometry method. RESULTS: Bioavailability was 0.54 (0.45-0.63) for the 0.8 mg and 0.52 (0.37-0.67) for the 1.6 mg nasal naloxone formulation. Maximum concentration levels (C max) were 1.45 ng/ml (1.07-1.84) for 0.8 mg and 2.57 ng/ml (1.49-3.66) for the 1.6 mg. Time to maximum concentrations (T max) were reached at 17.9 min (11.4-24.5) and 18.6 min (14.4-22.9) for the 0.8 mg and the 1.6 mg doses, respectively. CONCLUSION: This nasal naloxone formulation had a rapid, systemic uptake and higher bioavailability than naloxone formulations not designed for IN use. This indicates that an optimized high-concentration/low-volume nasal spray formulation may deliver a therapeutic dose. The 1.6 mg nasal dose provided serum concentrations that surpassed those of 1.0 mg IV after 15-20 min and stayed above for the rest of the study period120765+ field[33]: Not in File!?$Undheim, E.A.B. Fry, B.G. King, G.F.2015BCentipede venom: recent discoveries and current state of knowledge679-704Toxins73ANALYTICAL ANIMAL Animals ARTHROPOD author CENTIPEDE complications ENVENOMATION evolution family HUMAN INFORMATION IS Knowledge LIMB Modified NO POISONING PROTEIN proteins REVIEW STING Venom2015Centipedes are among the oldest extant venomous predators on the planet. Armed with a pair of modified, venom-bearing limbs, they are an important group of predatory arthropods and are infamous for their ability to deliver painful stings. Despite this, very little is known about centipede venom and its composition. Advances in analytical tools, however, have recently provided the first detailed insights into the composition and evolution of centipede venoms. This has revealed that centipede venom proteins are highly diverse, with 61 phylogenetically distinct venom protein and peptide families. A number of these have been convergently recruited into the venoms of other animals, providing valuable information on potential underlying causes of the occasionally serious complications arising from human centipede envenomations. However, the majority of venom protein and peptide families bear no resemblance to any characterised protein or peptide family, highlighting the novelty of centipede venoms. This review highlights recent discoveries and summarises the current state of knowledge on the fascinating venom system of centipedes. Copyright © 2015 by the authors; licensee MDPI, Basel, Switzerland120814' field[33]: Not in Files?J Unger, J.R.2017 Staring down the opioid epidemic8Journal of Family Practice6615EPIDEMIC OPIOID Opioid overdose Opioids OVERDOSE Time1/2017120898^ Not in File)?CVachon, J. Campagna, C. Rodriguez, M.J. Sirard, M.-A. Levallois, P.2017oBarriers to the use of toxicogenomics data in human health risk assessment: a survey of Canadian risk assessors119-123$Regulatory Toxicology & Pharmacology85ASSESSMENT Canada DATA Data quality Guidelines HEALTH Health risk Health risk assessment HUMAN Human health INFORMATION interpretation IS Knowledge quality QUESTIONNAIRE Regulatory RISK RISK ASSESSMENT SURVEY Toxicogenomics use 1/27/2017Regulatory agencies worldwide need to modernize human health risk assessment (HHRA) to meet challenges of the 21st century. Toxicogenomics is at the core of this improvement. Today, however, the use of toxicogenomics data in HHRA is very limited. The purpose of this survey was to identify barriers to the application of toxicogenomics data in HHRA by human health risk assessors. An online survey targeting Canadian risk assessors gathered information on their knowledge and perception of toxicogenomics, their current and future inclusion of toxicogenomics data in HHRA, and barriers to the use of such data. Twenty-nine (29) participants completed a questionnaire after 2 months of solicitation. The results show that the application of toxicogenomics data in Canada is marginal, with 85% of respondents reporting that they never or rarely used such data. Knowledge of toxicogenomics by Canadian risk assessors is also limited: about two-thirds of respondents (68%) were not at all or only slightly familiar with the concept. Lack of guidelines for toxicogenomics data interpretation, data quality assessment and on their use in HHRA, were found to be major barriers. In conclusion, there is a need for interventions aimed at facilitating the use of toxicogenomics data in HHRA, when available120809- field[33]: Not in File !?RVan den Brink, W. Emerenciana, A. Bellanti, F. Della Pasqua, O. van der Laan, J.W.2017gPrediction of thyroid C-cell carcinogenicity after chronic administration of GLP1-R agonists in rodents51-59#Toxicology and Applied Pharmacology320Tanalysis As Association Attention carcinogenic CARCINOGENICITY CHRONIC DATA DRUG drugs duration EXENATIDE EXPOSURE IN VITRO Incidence INDUCTION IS liraglutide LIXISENATIDE MECHANISM Mechanisms method methods MODEL PHARMACODYNAMICS pharmacokinetic PHARMACOKINETICS Potency PREDICTION Regulatory Rodents STUDY thyroid TREATMENT use Validation 2/16/2017Increased incidence of C-cell carcinogenicity has been observed for glucagon-like-protein-1 receptor (GLP-1r) agonists in rodents. It is suggested that the duration of exposure is an indicator of carcinogenic potential in rodents of the different products on the market. Furthermore, the role of GLP-1-related mechanisms in the induction of C-cell carcinogenicity has gained increased attention by regulatory agencies. This study proposes an integrative pharmacokinetic/pharmacodynamic (PKPD) framework to identify explanatory factors and characterize differences in carcinogenic potential of the GLP-1r agonist products. PK models for four products (exenatide QW (once weekly), exenatide BID (twice daily), liraglutide and lixisenatide) were developed using nonlinear mixed effects modelling. Predicted exposure was subsequently linked to GLP-1r stimulation using in vitro GLP-1r potency data. A logistic regression model was then applied to exenatide QW and liraglutide data to assess the relationship between GLP-1r stimulation and thyroid C-cell hyperplasia incidence as pre-neoplastic predictor of a carcinogenic response. The model showed a significant association between predicted GLP-1r stimulation and C-cell hyperplasia after 2years of treatment. The predictive performance of the model was evaluated using lixisenatide, for which hyperplasia data were accurately described during the validation step. The use of a model-based approach provided insight into the relationship between C-cell hyperplasia and GLP-1r stimulation for all four products, which is not possible with traditional data analysis methods. It can be concluded that both pharmacokinetics (exposure) and pharmacodynamics (potency for GLP-1r) factors determine C-cell hyperplasia incidence in rodents. Our work highlights the pharmacological basis for GLP-1r agonist-induced C-cell carcinogenicity. The concept is promising for application to other drug classes121122, field[33]: Not in File a?Van Hooste, W.L.2017SMyoclonic seizure prior to diagnosis of chronic toxic encephalopathy: a case report36Journal of Medical Case Reports111+ACID AIR AIRWAY biological BIOLOGICAL MONITORING case CASE REPORT Case-report central nervous system CHRONIC computed tomography DIAGNOSIS ENCEPHALOPATHY EPILEPSY EXPOSURE Imaging impact INDUSTRIAL IS Knowledge LIMB limits Long term Long-term MAGNETIC RESONANCE magnetic resonance imaging METABOLITE MONITORING NEUROLOGICAL NEUROTOXICITY NO OCCUPATIONAL OCCUPATIONAL EXPOSURE Occurrence ORGANIC ORGANIC SOLVENT organic solvents PATIENT REMOVAL seizure SEIZURES SOLVENT solvent exposure Solvents TOLUENE TOMOGRAPHY toxic toxic effects urinary use workplace2/7/2017K BACKGROUND: "Thinner" is a widely used industrial mixture of organic solvents. Exposure to organic solvents is usually not considered to be a possible cause of epilepsy, despite descriptions of toxic effects on the central nervous system. There are only a few reports about a possible epileptogenic effect of organic solvents exposure. We report a case of myoclonic seizure at the workplace that shows a remarkable coincidence between exposure to a thinner mixture and the occurrence of an epileptic seizure. CASE PRESENTATION: We present the case of a 50-year-old Belgian woman exposed to organic solvents for more than 20 years in a paintbrush manufactory. In 2009, her biological monitoring of hippuric acid (primary urinary metabolite of toluene) exceeded the threshold limit value of the American Conference of Governmental Industrial Hygienists. In 2012, after a period of high organic solvents exposure without the use of proper collective or personal airway protection, she had a seizure with myoclonic movements of her four limbs and loss of consciousness at her workplace. An electroencephalogram, computed tomography and magnetic resonance imaging of her head were within limits. Non-toxicological and toxicological causes were investigated. Her seizures did not reappear after workplace removal. Two years after her epileptic insult she was diagnosed with chronic toxic encephalopathy type 2b. In 2015, volatile organic compounds were measured at her workplace. Multiple (3/18) air samples exceeded the Belgian time-weighted average over 8 hours (77 mg/m3) for toluene. CONCLUSIONS: Knowledge about the impact of solvent exposure on the occurrence of epileptic insults is lacking. Long-term exposure to organic solvents is usually not considered to be a possible cause of epileptic seizure. But epileptic discharges have been described on electroencephalogram recordings for patients with chronic toxic encephalopathy. Myoclonic encephalopathy has been reported in toxic conditions. This case emphasizes a possible unusual neurological presentation of occupational exposure to organic solvents. It may be explained by lowering of the threshold for seizures due to high solvents exposure, most probably by toluene. This case suggests a chronological connection between a high occupational exposure to solvents and an epileptic insult. We found no other plausible cause120899+ field[33]: Not in File?JEvan Rhee, K.P. van Bentum, R. van Keulen, K. Kuypers, M.I. Haak, M.B.2017.Een patiënt met ernstige digoxine-intoxicatieD839'Nederlands Tijdschrift voor Geneeskunde161tABSORPTION ANTIBODIES ARREST ARRHYTHMIA Arrhythmias As ATRIAL FIBRILLATION CARDIAC CARDIAC ARREST CARDIAC ARRHYTHMIA CARDIAC GLYCOSIDE case DIGOXIN DISEASE FAILURE GLYCOSIDE HEART heart failure history HYPERKALAEMIA HYPOKALAEMIA INGESTION IS Man MEMBRANE MET Nausea PATIENT PREVENTION Reduction RESUSCITATION SYMPTOMS Toxicities TOXICITY TREATMENT VENTRICULAR FIBRILLATION2017BACKGROUND: Digoxin is a cardiac glycoside that is frequently prescribed in atrial fibrillation and heart failure. Symptoms such as nausea, hyperkalaemia, cardiac arrhythmias and cardiac arrest are seen in digoxin toxicity. The treatment focuses on reduction of digoxin absorption, prevention of hypokalaemia and hyperkalaemia, treatment of symptoms and, in severe toxicity, administration of digoxin antibodies. CASE DESCRIPTION: A 73-year-old man with a history of extensive cardiac disease was seen 45 minutes after ingesting 20 mg of digoxin. The patient developed ventricular fibrillation within 3 hours of ingestion, before arrival of the digoxin antibodies. The patient passed away despite resuscitation and administration of an insufficient amount of digoxin antibodies. CONCLUSION: The national supply of digoxin antibodies in the Netherlands proved to be too limited for the treatment of a patient with severe digoxin toxicity. An increase in the supply, and central storage, of digoxin antibodies could promote faster administration of an adequate amount of the antibodies. Timely transportation to an extra corporeal membrane oxygenation centre should also be considered121179K field[22]: [A patient with severe digoxin toxicity]. In Dutch with English abstract Not in File B?gVarghese, M.V. Abhilash, M. Alex, M. Sauganth Paul, M.V. Prathapan, A. Raghu, K.G. Harikumaran Nair, R.2017`Attenuation of arsenic trioxide induced cardiotoxicity through flaxseed oil in experimental rats Redox Report0online early: doi: 10.1080/13510002.2017.1289313not published, 01 Mar 17ACID ACUTE Adverse adverse event Adverse events agent Alpha-linolenic acid analysis ANTIOXIDANT antioxidant enzymes ARSENIC ARSENIC TRIOXIDE As CANCER CARDIAC cardiac toxicity CARDIOTOXICITY CLINICAL Content DRUG EFFICACY ENZYME EXPERIMENTAL GA GAS GLUTATHIONE HEALTH HEART IS LEUKAEMIA LIPID LIPID PEROXIDATION MALE method methods OIL PATIENT PEROXIDATION RAT rats Release SPECTROMETRY THERAPY TISSUE Toxicities TOXICITY TREATMENT TRIAL Wistar rat Wistar rats 2/17/2017OBJECTIVES: Arsenic trioxide (As2O3) is a potent drug for acute promyelocytic leukaemia, but its clinical trials are allied with some serious adverse events mainly cardiac functional abnormalities. So the objective of our investigation is to identify the cardioprotective action of flaxseed oil (FSO), a natural compound against As2O3 induced cardiotoxicity. METHODS: Male wistar rats were treated with As2O3 (4 mg/kg) to induce cardiotoxicity. FSO (250 and 500 mg/kg) was given in combination with As2O3 for evaluating its cardioprotective efficacy. RESULTS: Treatment with As2O3 resulted in deposition of arsenic in heart tissue, increased cardiac marker enzymes release, lipid peroxidation (LPO), oxidative insults and pathological damages in the heart. Co-treatment with FSO (500 mg/kg) significantly reduced the arsenic accumulation, cardiac marker enzymes, LPO and cardiac structural alterations. FSO treatment significantly improved cardiac glutathione content, antioxidant enzymes and reduced the pathological damages in cardiac tissue. Gas chromatographic-mass spectrometry analysis revealed that the major fatty acid content in the FSO is alpha-linolenic acid, which has a strong milieu in cardiac health. CONCLUSION: The results of the current investigation suggested that FSO is an effective agent in reducing arsenic-induced cardiac toxicity and can be used as an adjunct/dietary supplement for the cancer patients on As2O3 therapy121099/ field[33]: Not in File?LVentura, C. Núñez, M. Gaido, V. Pontillo, C. Miret, N. Randi, A. Cocca, C.2017cHexachlorobenzene alters cell cycle by regulating p27-cyclin E-CDK2 and c-Src-p27 protein complexes72-79Toxicology Letters270As BREAST CANCER CANCER CELL CELL PROLIFERATION CONCENTRATIONS ENDOCRINE Endocrine disruptor Environment Hand HEXACHLOROBENZENE INTERACTION IS Mammary MECHANISM Mechanisms Mechanisms of action ORGANOCHLORINE Pollutant PROTEIN RAT rats Time TUMOUR 2/12/2017Hexachlorobenzene (HCB) is an organochlorine pollutant widely distributed in the environment around the entire world. Previous reports from our group and others have demonstrated that this compound is as an endocrine disruptor. We have also reported that HCB presents a co-carcinogenic effect in N-Nitroso-N-methyl-urea-induced mammary tumours in rats. In this work, we studied the effects of HCB on cell cycle progression and cell cycle regulating protein expression in the estrogen-sensitive breast cancer cell line, MCF-7. Here, we show that HCB alters cell cycle in a concentration-dependent way. The lowest assessed concentration (0.005muM) promotes the cell cycle progression, enhances cyclin D1 expression, and reduces the nuclear localization of p27 accompanied by an increased interaction between p27 and c-Src kinase. On the other hand, 5muM HCB delays the cell cycle progression and promotes the formation of the cyclin E-CDK2-p27 protein complex. Our results show that HCB stimulates cell proliferation through cell cycle modulation and c-Src involvement in MCF-7 cells. Here, we report for the first time that differential mechanisms of action of HCB on mammary cell cycle progression are triggered at different concentrations of this pollutant121127. field[33]: Not in FileB?JVikrant, S. Parashar, A.2017WSnake bite-induced acute kidney injury: report of a successful outcome during pregnancy/American Journal of Tropical Medicine & Hygiene(online early: doi: 10.4269/ajtmh.17-0007not published, 28 Feb 176ACUTE Acute kidney injury Adverse ADVERSE EFFECTS case child DEATH Development ENVENOMATION FETAL HAZARD HEALTH Health hazard hemodialysis injuries Injury IS KIDNEY kidney injury MANAGEMENT MORBIDITY MORTALITY NEPHROTOXICITY outcome PREGNANCY snake bite snake envenomation THERAPY toxic toxic effects Venom WHO2/6/2017Snake bite is an important health hazard in tropics. Snake envenomation in pregnancy may cause fetal death and maternal mortality or morbidity. However, little is known about the toxic effects and optimal management during pregnancy after snake envenomation because of the rarity of cases. Herein, we report a case of a pregnant woman who was successfully treated for snake bite-induced acute kidney injury during the third trimester. She was treated with equine-derived polyvalent anti-snake venom without development of any adverse effects, hemodialysis, and supportive therapy. She fully recovered and subsequently gave birth to a healthy child120854' field[33]: Not in File B?dVilain, P. Larrieu, S. Mougin-Damour, K. Marianne Dit Cassou, P.-J. Weber, M. Combes, X. Filleul, L.2017Emergency department syndromic surveillance to investigate the health impact and factors associated with alcohol intoxication in Reunion IslandEmergency Medicine early: doi: 10.1136/emermed-2015-204987#not published, 28 Feb 17, 17 Mar 17&Additive Age ALCOHOL Alcohol use analysis Association Benefits burden DATA DISEASE Emergencies emergency EMERGENCY DEPARTMENT EPIDEMIOLOGY HEALTH impact INTOXICATION IS Knowledge Long term Long-term men method methods MODEL PUBLIC Reunion Island School SOCIAL STUDY SURVEILLANCE time series use 2/10/2017In Reunion Island, alcohol is the most tried out psychoactive substance. To our knowledge, few indicators measuring the health burden of alcohol use exist on the island. In this context, an exploratory analysis based on syndromic surveillance data was implemented in order to describe the emergency department (ED) visits for alcohol intoxication (AI) and factors associated with their variations.An analysis of anonymized records routinely collected by the syndromic surveillance system was carried out. A daily indicator of ED visits for AI was built from a selection of ICD-10 codes between 2010 and 2012. Health impact of AI was first described comparing this indicator to all causes ED visits. Then, AI visits were analyzed with time-series methods using generalized additive Poisson regression models allowing for overdispersion. The following variables were included in the model: long-term trend, seasonality, day of the week, public and school holidays, days of festival and minimum social benefits payday.During the study period, 16 652 visits for AI were recorded in EDs of Reunion Island. AI visits were the second reason for ED visits (i.e. 4%) after traumatism. AI visits mainly concerned men (87%) and the age group of 25-54 years (69%). There was a significant increase in ED visits for AI during days of benefits payday, weekends and publics holidays.This study demonstrated the interest of syndromic surveillance to monitor non-infectious diseases. Time-series models showed a robust association between ED visits for AI and several factors120876- field[33]: Not in File ?4Voorhees, J.R. Rohlman, D.S. Lein, P.J. Pieper, A.A.2016ZNeurotoxicity in preclinical models of occupational exposure to organophosphorus compounds590Frontiers in Neuroscience10ACETYLCHOLINE ACETYLCHOLINESTERASE ACUTE ANIMAL Animals As Association CHOLINERGIC Cholinergic crisis DISEASE ENZYME epidemiological evidence EXPERIMENTAL EXPOSURE Guidelines HUMAN Humans ILLNESS INSECTICIDE Insecticides IS LEVELS MECHANISM Mechanisms method methods MODEL NEUROLOGICAL NEUROTOXICITY OCCUPATIONAL OCCUPATIONAL EXPOSURE op organophosphate Organophosphates organophosphorus organophosphorus compound ORGANOPHOSPHORUS COMPOUNDS Plasticizers PSYCHIATRIC REVIEW RISK SEQUELAE STUDY synapse TREATMENT workplace2016Organophosphorus (OPs) compounds are widely used as insecticides, plasticizers, and fuel additives. These compounds potently inhibit acetylcholinesterase (AChE), the enzyme that inactivates acetylcholine at neuronal synapses, and acute exposure to high OP levels can cause cholinergic crisis in humans and animals. Evidence further suggests that repeated exposure to lower OP levels insufficient to cause cholinergic crisis, frequently encountered in the occupational setting, also pose serious risks to people. For example, multiple epidemiological studies have identified associations between occupational OP exposure and neurodegenerative disease, psychiatric illness, and sensorimotor deficits. Rigorous scientific investigation of the basic science mechanisms underlying these epidemiological findings requires valid preclinical models in which tightly-regulated exposure paradigms can be correlated with neurotoxicity. Here, we review the experimental models of occupational OP exposure currently used in the field. We found that animal studies simulating occupational OP exposures do indeed show evidence of neurotoxicity, and that utilization of these models is helping illuminate the mechanisms underlying OP-induced neurological sequelae. Still, further work is necessary to evaluate exposure levels, protection methods, and treatment strategies, which taken together could serve to modify guidelines for improving workplace conditions globally120768* field[33]: Not in File??Wang, D.Y. Okoye, G.D. Neilan, T.G. Johnson, D.B. Moslehi, J.J.2017@Cardiovascular toxicities associated with cancer immunotherapies21Current Cardiology Reports193eACUTE Adverse adverse event Adverse events ANTIBODIES As CANCER CARDIAC CARDIOTOXICITY CARDIOVASCULAR Cardiovascular toxicity case CELL CLINICAL Clinical outcome CORTICOSTEROIDS DRIVING DRUG drugs IMMUNOTHERAPY Incidence IS LEAD MANAGEMENT MECHANISM Mechanisms MONOCLONAL ANTIBODIES MYOCARDITIS outcome REVIEW SCREENING STUDY THERAPY Toxicities TOXICITY use3/2017PURPOSE OF REVIEW: We review the cardiovascular toxicities associated with cancer immune therapies and discuss the cardiac manifestations, potential mechanisms, and management strategies. RECENT FINDINGS: The recent advances in cancer immune therapy with immune checkpoint inhibitors and adoptive cell transfer have improved clinical outcomes in numerous cancers. The rising use of cancer immune therapy will lead to a higher incidence in immune-related adverse events. Recent studies have highlighted several reports of severe cases of acute cardiotoxic events with immune therapy including fulminant myocarditis. We believe that immune-mediated myocarditis is a driving mechanism behind these cardiovascular toxicities and requires vigilant screening and prompt management with corticosteroids and immune-modulating drugs, especially with combination immune therapies. While the incidence of serious cardiovascular toxicities with immune therapy appears low, these can be life-threatening especially when manifesting as acute immune-mediated myocarditis. Further collaborative studies are needed to effectively identify, characterize, and manage these events120974+ field[33]: Not in File B?%Wang, I.-J. Karmaus, W.J. Yang, C.-C.2017SPolycyclic aromatic hydrocarbons exposure, oxidative stress, and asthma in children?International Archives of Occupational and Environmental Health,online early: doi: 10.1007/s00420-017-1198-ynot published, 28 Feb 17-analysis AROMATIC HYDROCARBONS Association ASTHMA BETA Biomarker carcinogenic CHILDREN DISEASE ELISA EXPOSURE HYDROCARBON IGE INFORMATION IS LEVELS method methods OXIDATIVE STRESS P PAEDIATRIC PAH PATHOGENESIS POLYCYCLIC AROMATIC HYDROCARBONS RESPIRATORY RISK SERUM STRESS teratogenic UPLC-MS/MS URINE2/7/2017cPURPOSE: Polycyclic aromatic hydrocarbons (PAHs) are known for their carcinogenic and teratogenic properties. However, little is known about the effect of PAH on our immune and respiratory systems. Hence, we investigated associations (1) between PAH exposure and IgE levels and asthma in children and (2) between PAH exposure and the oxidative stress marker 8OHdG potentially involved in disease pathogenesis stratifying by (3) sex-based differences. METHODS: A total of 453 kindergarten children were recruited and provided samples. Urine biomarker of PAH exposure (1-OHP levels) was measured by UPLC-MS/MS and a marker of oxidative stress (8OHdG) was measured by ELISA. Serum IgE were assessed and information on asthma was collected. Associations between 1-OHP levels, 8OHdG, IgE and asthma were analyzed by multivariate linear and logistic regression. A mediation analysis was conducted to evaluate whether the risk of increased IgE and asthma related to PAH exposure is explained by 8OHdG changes. RESULTS: Urine 1-OHP levels were positively related to 8OHdG levels (per ln-unit: beta = 0.30kU/l, p = 0.002). Similar results were also found for 1-OHP levels with IgE levels (per ln-unit: beta = 0.27 kU/l, p = 0.027). 1-OHP levels (per ln-unit) were significantly associated with asthma, with an OR (95% CI) of 1.42 (1.18-1.70). In addition, 1-OHP levels were associated with asthma. It is estimated that 35% of the effect of PAH exposure on asthma is mediated by 8OHdG levels. CONCLUSION: Exposure to PAH may enhance oxidative stress and may induce asthma. The effect of PAH exposure on asthma may be mediated by oxidative stress120887+ field[33]: Not in File ?$Wang, J. Schlagenhauf, L. Setyan, A.2017Transformation of the released asbestos, carbon fibers and carbon nanotubes from composite materials and the changes of their potential health impacts15Journal of Nanobiotechnology151As ASBESTOS ASSESSMENT carbon Carbon nanotubes Environment HEALTH Health impacts HUMAN Human health impact NANOPARTICLES Nanotubes Reinforcement Release RISK RISK ASSESSMENT safe Stability STUDY Toxicities TOXICITY TREATMENT 2/20/2017Composite materials with fibrous reinforcement often provide superior mechanical, thermal, electrical and optical properties than the matrix. Asbestos, carbon fibers and carbon nanotubes (CNTs) have been widely used in composites with profound impacts not only on technology and economy but also on human health and environment. A large number of studies have been dedicated to the release of fibrous particles from composites. Here we focus on the transformation of the fibrous fillers after their release, especially the change of the properties essential for the health impacts. Asbestos fibers exist in a large number of products and the end-of-the-life treatment of asbestos-containing materials poses potential risks. Thermal treatment can transform asbestos to non-hazardous phase which provides opportunities of safe disposal of asbestos-containing materials by incineration, but challenges still exist. Carbon fibers with diameters in the range of 5-10 mum are not considered to be respirable, however, during the release process from composites, the carbon fibers may be split along the fiber axis, generating smaller and respirable fibers. CNTs may be exposed on the surface of the composites or released as free standing fibers, which have lengths shorter than the original ones. CNTs have high thermal stability and may be exposed after thermal treatment of the composites and still keep their structural integrity. Due to the transformation of the fibrous fillers during the release process, their toxicity may be significantly different from the virgin fibers, which should be taken into account in the risk assessment of fiber-containing composites121052. field[33]: Not in FileB?9Wang, J. Sun, F. Tang, S. Zhang, S. Lv, P. Li, J. Cao, X.2017RSafety assessment of vitacoxib: acute and 90-day sub-chronic oral toxicity studies&Regulatory Toxicology and early: doi: 10.1016/j.yrtph.2017.02.020not published, 01 Mar 17ACUTE Acute toxicity Additive As ASSESSMENT DATA DIET dose EXPERIMENTAL HISTOPATHOLOGY HUMAN IS KIDNEY LIVER MICE NO NOAEL NSAID ORAL RAT rats SAFETY safety assessment STUDY SUBCHRONIC Subchronic toxicity TEST Toxicities TOXICITY Toxicity study use 2/24/2017Vitacoxib, is a newly developed coxibs NSAID (selective inhibitors of cyclooxygenase-2). To date, no experimental data have been published concerning its safety for use as an additive in the human diet. In the present study, we assessed the acute and sub-chronic toxicity of vitacoxib administered by gavage. The acute toxicity tests in Sprague Dawley (SD) rats and ICR mice demonstrated that vitacoxib at a dose of 5000 mg/kg BW failed to alter any of the parameters studied. In the 90-day sub-chronic toxicity test, vitacoxib was administered to SD rats at the doses of 0 (control), 5, 10, 20, 30, and 60 mg/kg BW. The results demonstrated that there were no significant differences for most indexes of sub-chronic toxicity throughout the experiment at the dose of 5-20 mg/kg BW, indicating no apparent dose-dependent. However, there were significant histopathology changes in the liver and kidney, and alterations in some biochemical parameters in the 60 mg/kg BW group. Based on these findings, the gavage LD50 was determined to be > 5000 mg/kg in SD rats and ICR mice, and the 90-day gavage no-observed-adverse-effect level (NOAEL) of vitacoxib was considered to be 20 mg/kg BW under the present study conditions121102- field[33]: Not in File?(Wang, P. Pradhan, K. Zhong, X.-B. Ma, X.2016'Isoniazid metabolism and hepatotoxicity384-392Acta Pharmaceutica Sinica B65Association FAILURE HEPATOTOXICITY INH injuries Injury IS ISONIAZID LIVER Liver failure liver injury MANAGEMENT METABOLISM Pathway REVIEW TUBERCULOSIS2016GIsoniazid (INH) is highly effective for the management of tuberculosis. However, it can cause liver injury and even liver failure. INH metabolism has been thought to be associated with INH-induced liver injury. This review summarized the metabolic pathways of INH and discussed their associations with INH-induced liver injury.120687, field[33]: Not in Filef?JYWang, X. Li, Z. Berglass, J. He, W. Zhao, J. Zhang, M. Gao, C. Zhang, C. Zhang, H. Yi, X.2016YMRI and clinical manifestations of delayed encephalopathy after carbon monoxide poisoning 2317-2320+Pakistan Journal of Pharmaceutical Sciences296(Suppl)+As BASAL GANGLIA BRAIN Brain MRI carbon CARBON MONOXIDE carbon monoxide poisoning Chorea CLINICAL CO cognitive ENCEPHALOPATHY Globus pallidus IMPAIRMENT injuries Injury INTOXICATION LESIONS MAGNETIC RESONANCE MRI NEUROLOGICAL NEUROTOXICITY PARKINSONISM PATIENT POISONING Syndrome Toxicities TOXICITY11/2016vTo explore the relationship between the clinical manifestations and functional magnetic resonance images of delayed encephalopathy after carbon monoxide intoxication. Six patients received the MRI were diagnosed with delayed encephalopathy after carbon monoxide (CO) poisoning. Clinical manifestations were observed in each patient. MRI revealed multiple lesions. The majority of the lesions were located in the globus pallidus, sub cortical white matter, and basal ganglia. The cognitive injury, akinetic mutism, fecal and uroclepsia, forced crying, forced laughing and extra pyramidal syndromes such as chorea and parkinsonism were manifested in clinic. Cognitive impairment improved greatly while involuntary movements only improved slightly after several months. Meanwhile brain MRI suggested remarkable improvement. Neuroimaging directly correlated with the clinical manifestations120914: Not in File jB?dWang, Y.-Y. Li, J. Wu, Z.-r. Zhang, B. Yang, H.-B. Wang, Q. Cai, Y.-c. Liu, G.-x. Li, W.-H. Tang, Y.2017Insights into the molecular mechanisms of Polygonum multiflorum Thunb-induced liver injury: a computational systems toxicology approachActa Pharmacologica Sinica'online early: doi: 10.1038/aps.2016.147not published, 01 Mar 17ABSORPTION ACID analysis apoptosis As BILE case chemical CHEMICALS CLINICAL CYTOCHROME CYTOCHROME P450 DATA DATABASE DISEASE DISTRIBUTION ENZYME GLUTATHIONE HEPATITIS Hepatotoxic HEPATOTOXICITY Herb HERBAL MEDICINE IDENTIFICATION injuries Injury INTERACTION Intestinal Absorption LIVER LIVER DISEASE liver injury MECHANISM Mechanisms Medicine medicines METABOLISM method mRNA expression P450 Pathway PREDICTION SCREENING STUDY SYMPTOMS systems toxicology toxic Toxicities TOXICITY TOXICOLOGY URINE 2/27/2017An increasing number of cases of herb-induced liver injury (HILI) have been reported, presenting new clinical challenges. In this study, taking Polygonum multiflorum Thunb (PmT) as an example, we proposed a computational systems toxicology approach to explore the molecular mechanisms of HILI. First, the chemical components of PmT were extracted from 3 main TCM databases as well as the literature related to natural products. Then, the known targets were collected through data integration, and the potential compound-target interactions (CTIs) were predicted using our substructure-drug-target network-based inference (SDTNBI) method. After screening for hepatotoxicity-related genes by assessing the symptoms of HILI, a compound-target interaction network was constructed. A scoring function, namely, Ascore, was developed to estimate the toxicity of chemicals in the liver. We conducted network analysis to determine the possible mechanisms of the biphasic effects using the analysis tools, including BiNGO, pathway enrichment, organ distribution analysis and predictions of interactions with CYP450 enzymes. Among the chemical components of PmT, 54 components with good intestinal absorption were used for analysis, and 2939 CTIs were obtained. After analyzing the mRNA expression data in the BioGPS database, 1599 CTIs and 125 targets related to liver diseases were identified. In the top 15 compounds, seven with Ascore values >3000 (emodin, quercetin, apigenin, resveratrol, gallic acid, kaempferol and luteolin) were obviously associated with hepatotoxicity. The results from the pathway enrichment analysis suggest that multiple interactions between apoptosis and metabolism may underlie PmT-induced liver injury. Many of the pathways have been verified in specific compounds, such as glutathione metabolism, cytochrome P450 metabolism, and the p53 pathway, among others. Hepatitis symptoms, the perturbation of nine bile acids and yellow or tawny urine also had corresponding pathways, justifying our method. In conclusion, this computational systems toxicology method reveals possible toxic components and could be very helpful for understanding the mechanisms of HILI. In this way, the method might also facilitate the identification of novel hepatotoxic herbs120930& field[33]: Not in FileB?1Wang, Z. Dewitt, J.C. Higgins, C.P. Cousins, I.T.2017DA never-ending story of per- and polyfluoroalkyl substances (PFASs)?"Environmental Science & Technology*online early: doi: 10.1021/acs.est.6b04806not published, 01 Mar 17|ACID Environment IS PERFLUOROALKYL perfluorooctanoic acid PFOA PFOS Polyfluoroalkyl substances PRECURSOR Regulation RESEARCH 2/22/2017#More than 3000 per- and polyfluoroalkyl substances (PFASs) are, or have been, on the global market, yet most research and regulation continues to focus on a limited selection of rather well-known long-chain PFASs, particularly perfluorooctanesulfonate (PFOS), perfluorooctanoic acid (PFOA) and their precursors. Continuing to overlook the vast majority of other PFASs is a major concern for society. We provide recommendations for how to proceed with research and cooperation to tackle the vast number of PFASs on the market and in the environment120988) field[33]: Not in File ?1Watson, S.B. Zastepa, A. Boyer, G.L. Matthews, E.2017@Algal bloom response and risk management: on-site response tools144-152Toxicon129ALGAE ANALYTICAL ASSAY CYANOBACTERIA DETECTION EXPOSURE HEALTH Inhibition LEVELS MANAGEMENT MET method methods MONITORING Operative PROTEIN PROTEIN PHOSPHATASE PUBLIC PUBLIC HEALTH quality RISK RISK MANAGEMENT SAFETY SCREENING SERVICE TEST Time Toxicities TOXICITY toxin TOXINS WATER 2/13/2017Harmful algal blooms caused by cyanobacteria can present a risk to the safety of drinking- and recreational waters and beachfronts through the production of toxins, particularly microcystin, which are highly resilient to degradation. These blooms are difficult to predict, vary in appearance and toxicity, and can show significant spatial heterogeneity: wind- and current-borne scums can produce an order of magnitude range in toxin levels along shorelines. The growing demand for reliable, cost-effective and rapid methods to detect toxins in bloom material and reduce the risk of public exposure cannot be met by most analytical lab turnaround times. Commercial microcystin test kits are now available, but few have been rigorously field-tested or incorporated into monitoring programmes. Working with a local health agency, we evaluated two kits with different operative ranges of detection, applied to samples covering a wide range of water quality, sample matrices, and bloom composition. We compared their performance against lab analyses using Enzyme-Linked Immunosorbent and Protein Phosphatase Inhibition assays. Both kits could resolve samples with high (<10 mug/L microcystin equivalents (MCequiv)) and low/no toxins, but failed to reliably detect toxin levels between 1 and 5 mug/L, at which threshold there were few false negatives (8%) but approximately one third of the samples (32%) yielded false positives. We conclude that these kits are potentially useful for screening and informed risk management decisions e.g. on beach closures, but should be followed up with more rigorous tests where needed. We describe how, based on these results, the kits have been successfully incorporated into the routine municipal beach monitoring and advisory programme by the Hamilton Public Health Services (Ontario)121141/ field[33]: Not in Filex?LWatzek, N. Berger, F. Kolle, S.N. Kaufmann, T. Becker, M. van Ravenzwaay, B.2017Assessment of skin sensitization under REACH: a case report on vehicle choice in the LLNA and its crucial role preventing false positive results25-32$Regulatory Toxicology & Pharmacology85analysis As ASSAY ASSESSMENT case CASE REPORT case studies Case Study Case-report chemical CHEMICALS CHEMISTRY DATA DERMAL False-positive IN VIVO IS MCDA method OIL PROPYLENE PROPYLENE GLYCOL REACH Regulation SENSITIZATION SKIN STUDY TEST Testing Vehicle Volume 1/31/2017In the EU, chemicals with a production or import volume in quantities of one metric ton per year or more have to be tested for skin sensitizing properties under the REACH regulation. The murine Local Lymph Node Assay (LLNA) and its modifications are widely used to fulfil the data requirement, as it is currently considered the first-choice method for in vivo testing to cover this endpoint. This manuscript describes a case study highlighting the importance of understanding the chemistry of the test material during testing for 'skin sensitization' of MCDA (mixture of 2,4- and 2,6-diamino-methylcyclohexane) with particular focus on the vehicle used. While the BrdU-ELISA modification of the LLNA using acetone/olive oil (AOO) as vehicle revealed expectable positive results. However, the concentration control analysis unexpectedly revealed an instability of MCDA in the vehicle AOO. Further studies on the reactivity showed MCDA to rapidly react with AOO under formation of various imine structures, which might have caused the positive LLNA result. The repetition of the LLNA using propylene glycol (PG) as vehicle did not confirm the positive results of the LLNA using AOO. Finally, a classification of MCDA as skin sensitizer according to the Globally Harmonized System (GHS) was not justified120808- field[33]: Not in File!?LWeber, C. Pusch, S. Schollmeyer, D. Münster-Müller, S. Pütz, M. Opatz, T.2016:Characterization of the synthetic cannabinoid MDMB-CHMCZCA 2808-2815&Beilstein Journal of Organic Chemistry123CANNABINOID cannabinoids CANNABIS case Characterization COMPARISON DATA DESIGNER DRUGS HPLC HPLC method MASS SPECTROMETRY MDMB-CHMCZCA method NMR NMR SPECTROSCOPY NOVEL PSYCHOACTIVE SUBSTANCES seizure SEIZURES SPECTROMETRY SYNTHETIC CANNABINOID Synthetic cannabinoids Tandem Mass Spectrometry TECHNIQUE TEST2016The synthetic cannabinoid MDMB-CHMCZCA was characterized by various spectroscopic techniques including NMR spectroscopy and tandem mass spectrometry. The synthetic sample was found to be of S-configuration by VCD spectroscopy and comparison of the data with DFT calculations, while ECD spectroscopy was found to be inconclusive in this case. The enantiomeric purity of samples from test purchases and police seizures was assessed by a self-developed chiral HPLC method120701% field[33]: Not in FileU?Wei, Y. Zhu, J.2016VPara-dichlorobenzene exposure is associated with thyroid dysfunction in US adolescents238-243Journal of Pediatrics177 ADOLESCENT Adolescents Aged As Association CONCENTRATIONS DICHLOROBENZENE EXPOSURE HEALTH HORMONE IS LEVELS MECHANISM Mechanisms Mechanisms of action MODEL PAEDIATRIC PARADICHLOROBENZENE Population prevalence SERUM STUDY SURVEY thyroid urinary urinary concentration US2016zObjective To examine the association between exposure to para-dichlorobenzene, measured as urinary concentrations of 2,5-dichlorophenol (2,5-DCP), and thyroid function in US adolescents. Study design A nationally representative subsample of 618 adolescents aged 12-19 years in the 2007-2008 and 2011-2012 National Health and Nutrition Examination Survey was analyzed for the association of urinary 2,5-DCP with serum thyroid function measures using multivariate logistic and general linear regression models. Results After adjusting for potential confounders, we found a significantly positive association between urinary concentrations of 2,5-DCP and serum levels of thyroid-stimulating hormone and thyroglobulin in adolescents. Furthermore, urinary 2,5-DCP was associated with an increased prevalence of hypothyroidism in the study population. Conclusions This study demonstrates a potential relationship between para-dichlorobenzene exposure, measured as urinary 2,5-DCP, and thyroid dysfunction in adolescents; however, further studies are needed to confirm our findings and to elucidate mechanisms of action. Copyright © 2016 Elsevier Inc120831- field[33]: Not in File B?AWeiner, S.G. Mitchell, P.M. Temin, E.S. Langlois, B.K. Dyer, K.S.2017:Use of intranasal naloxone by basic life support providersPrehosp. Emerg Care0online early: doi: 10.1080/10903127.2017.1282562not published, 28 Feb 17Age Aged As DATA DISPOSITION dose Emergencies emergency EMERGENCY DEPARTMENT HEROIN HOSPITAL INTRANASAL MALE method methods NALOXONE NASAL OPIOID Opioid overdose Opioids outcome OVERDOSE PATIENT PROTOCOL REVIEW SERVICE STATISTICS STUDY use WHO2/6/2017STUDY OBJECTIVES: Intranasal delivery of naloxone to reverse the effects of opioid overdose by Advanced Life Support (ALS) providers has been studied in several prehospital settings. In 2006, in response to the increase in opioid-related overdoses, a special waiver from the state allowed administration of intranasal naloxone by Basic Life Support (BLS) providers in our city. This study aimed to determine: 1) if patients who received a 2-mg dose of nasal naloxone administered by BLS required repeat dosing while in the emergency department (ED), and 2) the disposition of these patients. METHODS: This was a retrospective review of patients transported by an inner-city municipal ambulance service to one of three academic medical centers. We included patients aged 18 and older that were transported by ambulance between 1/1/2006 and 12/12/2012 and who received intranasal naloxone by BLS providers as per a state approved protocol. Site investigators matched EMS run data to patients from each hospital's EMR and performed a chart review to confirm that the patient was correctly identified and to record the outcomes of interest. Descriptive statistics were then generated. RESULTS: A total of 793 patients received nasal naloxone by BLS and were transported to three hospitals. ALS intervened and transported 116 (14.6%) patients, and 11 (1.4%) were intubated in the field. There were 724 (91.3%) patients successfully matched to an ED chart. Hospital A received 336 (46.4%) patients, Hospital B received 210 (29.0%) patients, and Hospital C received 178 (24.6%) patients. Mean age was 36.2 (SD 10.5) years and 522 (72.1%) were male; 702 (97.1%) were reported to have abused heroin while 21 (2.9%) used other opioids. Nasal naloxone had an effect per the prehospital record in 689 (95.2%) patients. An additional naloxone dose was given in the ED to 64 (8.8%) patients. ED dispositions were: 507 (70.0%) discharged, 105 (14.5%) admitted, and 112 (15.5%) other (e.g., left against medical advice, left without being seen, or transferred). CONCLUSIONS: Only a small percentage of patients receiving prehospital administration of nasal naloxone by BLS providers required additional doses of naloxone in the ED and the majority of patients were discharged120920/ field[33]: Not in File ?J\Weiss, D. Tomasallo, C.D. Meiman, J.G. Alarcon, W. Graber, N.M. Bisgard, K.M. Anderson, H.A.2017aElevated blood lead levels associated with retained bullet fragments — United States, 2003-2012130-133MMWR665QADULT Aged As BLOOD Blood lead bullet burden case DATA DIAGNOSIS EPIDEMIOLOGY EXPOSURE FRAGMENTS GUNSHOT HEALTH injuries Injury IS LEAD Lead exposure LEVELS LOW LEVELS low-level MALE MONITORING OCCUPATIONAL POISONING PUBLIC PUBLIC HEALTH SAFETY SCREENING Source SURVEILLANCE SYMPTOMS Testing Toxicities TOXICITY UNITED STATES Young Adult 2/10/2017An estimated 115,000 firearm injuries occur annually in the United States, and approximately 70% are nonfatal (1). Retained bullet fragments (RBFs) are an infrequently reported, but important, cause of lead toxicity; symptoms are often nonspecific and can appear years after suffering a gunshot wound (2,3). Adult blood lead level (BLL) screening is most commonly indicated for monitoring of occupational lead exposure; routine testing of adults with RBFs is infrequent (3). States collaborate with CDC's National Institute for Occupational Safety and Health (NIOSH) to monitor elevated BLLs through the Adult Blood Lead Epidemiology and Surveillance (ABLES) program (4,5). To help assess the public health burden of RBFs, data for persons with BLLs >/=10 mug/dL reported to ABLES during 2003-2012 were analyzed. An RBF-associated case was defined as a BLL >/=10 mug/dL in a person with an RBF. A non-RBF-associated case was defined as a BLL >/=10 mug/dL without an RBF. During 2003-2012, a total of 145,811 persons aged >/=16 years with BLLs >/=10 mug/dL were reported to ABLES in 41 states. Among these, 457 RBF-associated cases were identified with a maximum RBF-associated BLL of 306 mug/dL. RBF-associated cases accounted for 0.3% of all BLLs >/=10 mug/dL and 4.9% of BLLs >/=80 mug/dL. Elevated BLLs associated with RBFs occurred primarily among young adult males in nonoccupational settings. Low levels of suspicion of lead toxicity from RBFs by medical providers might cause a delay in diagnosis (3). Health care providers should inquire about an RBF as the potential cause for lead toxicity in an adult with an elevated BLL whose lead exposure is undetermined120908( field[33]: Not in FileB?0Weisser, K. Stubler, S. Matheis, W. Huisinga, W.2017ZTowards toxicokinetic modelling of aluminium exposure from adjuvants in medicinal products&Regulatory Toxicology and early: doi: 10.1016/j.yrtph.2017.02.018not published, 01 Mar 175ABSORPTION agent ALUMINIUM As ASSESSMENT BONE DATA DISPOSITION DISSOLUTION EXPERIMENTAL EXPOSURE GAP HUMAN Humans IN VITRO IN VIVO INTRAMUSCULAR IS KINETICS Knowledge MODEL pharmacokinetic PLASMA PREDICTION REVIEW RISK RISK ASSESSMENT SAFETY SUBCUTANEOUS THERAPY TISSUE toxic TOXICOKINETIC VACCINATION VACCINE 2/22/2017oAs a potentially toxic agent on nervous system and bone, the safety of aluminium exposure from adjuvants in vaccines and subcutaneous immune therapy (SCIT) products has to be continuously re-evaluated, especially regarding concomitant administrations. For this purpose, knowledge on absorption and disposition of aluminium in plasma and tissues is essential. Pharmacokinetic data after vaccination in humans, however, are not available, and for methodological and ethical reasons difficult to obtain. To overcome these limitations, we discuss the possibility of an in vitro-in silico approach combining a toxicokinetic model for aluminium disposition with biorelevant kinetic absorption parameters from adjuvants. We critically review available kinetic aluminium-26 data for model building and, on the basis of a reparameterized toxicokinetic model (Nolte et al., 2001), we identify main modelling gaps. The potential of in vitro dissolution experiments for the prediction of intramuscular absorption kinetics of aluminium after vaccination is explored. It becomes apparent that there is need for detailed in vitro dissolution and in vivo absorption data to establish an in vitro-in vivo correlation (IVIVC) for aluminium adjuvants. We conclude that a combination of new experimental data and further refinement of the Nolte model has the potential to fill a gap in aluminium risk assessment121100- field[33]: Not in File JB?QWickramatilake, S. Zur, J. Mulvaney-Day, N. von Klimo, M.C. Selmi, E. Harwood, H.2017)How States are tackling the opioid crisisPublic Health Reports+online early: doi: 10.1177/0033354916688206not published, 21 Feb 17wABUSE ADDICTION ALCOHOL ANTIDOTE Association DATA DRUG DRUG ABUSE EVIDENCE-BASED family Guidelines HEALTH maintenance medication assisted treatment medication-assisted treatment method methods MISUSE MONITORING NALOXONE OPIOID opioid addiction Opioids OVERDOSE pain PATIENT policy PRESCRIBING PUBLIC PUBLIC HEALTH QUESTIONNAIRE RISK safe Source TREATMENT UNITED STATES US use1/1/2017OBJECTIVES: We used data from the 2015 National Association of State Alcohol and Drug Abuse Directors Web-based questionnaire and other sources to demonstrate the range and scope of state initiatives being used to deal with the opioid crisis in the United States. METHODS: State alcohol and drug agency directors and designated senior agency managers responded to the questionnaire, which asked respondents about recent opioid-related state-level public health initiatives at their agencies. RESULTS: State alcohol and drug agencies in all 50 states and the District of Columbia responded, all of which reported that prescription drug misuse was a high priority or the highest priority area for their agencies. Of the 51 respondents, states reported initiatives to educate the general public (n = 48), prescribers (n = 31), patients and families (n = 24), and pharmacists (n = 22) about the risks of opioids. In addition, 29 states had increased funding for medication-assisted treatment of opioid addiction, 28 had expanded the availability of naloxone (an opioid antidote), 26 had established guidelines for safe opioid prescribing, 23 had launched requirements for prescriber use of prescription monitoring programs, 23 had passed Good Samaritan laws to protect those helping treat overdoses, and 14 had enacted legislation to regulate pain clinics. CONCLUSIONS: US state alcohol and drug agencies demonstrated a robust response to the opioid crisis in the United States. They have pursued and expanded on an array of evidence-based initiatives aimed at the opioid crisis. Future public health efforts should focus on maintenance and further expansion of high-quality, evidence-based practices, policies, and programs120806* field[33]: Not in File+?Wijdicks, E.F.2017"Management of the comatose patient117-129Handbook of Clinical Neurology140ACUTE acute poisoning ANTIDOTE Antidotes As ASSESSMENT BRAIN CLINICAL COMA complications INTENSIVE CARE intensive care unit IS Laboratories LABORATORY MANAGEMENT Mechanical ventilation PATIENT POISONING PREVENTION TISSUE TREATMENT UNIT VENTILATION Vital signs2017tComa has many causes but there are a few urgent ones in clinical practice. Management must start with establishing the cause and an attempt to reverse or attenuate some of the damage. This may include early neurosurgical intervention, efforts to reduce brain tissue shift and raised intracranial pressure, correction of markedly abnormal laboratory abnormalities, and administration of available antidotes. Supporting the patient's vital signs, susceptible to major fluctuations in a changing situation, remains the most crucial aspect of management. Management of the comatose patient is in an intensive care unit and neurointensivists are very often involved. This chapter summarizes the principles of caring for the comatose patient and everything a neurologist would need to know. The basic principles of neurologic assessment of the comatose patient have not changed, but better organization can be achieved by grouping comatose patients according to specific circumstances and findings on neuroimaging. Ongoing supportive care involves especially aggressive prevention of medical complications associated with mechanical ventilation and prolonged immobility. Waiting for recovery-and many do- is often all that is left. Neurorehabilitation of the comatose patient is underdeveloped and may not be effective. There are, as of yet, few proven options for neurostimulation in comatose patients1208834 field[33]: Not in FileB?cWilliams, H.F. Vaiyapuri, R. Gajjeraman, P. Hutchinson, G. Gibbins, J.M. Bicknell, A. Vaiyapuri, S.2017tChallenges in diagnosing and treating snakebites in a rural population of Tamil Nadu, India: the views of cliniciansToxicon0online early: doi: 10.1016/j.toxicon.2017.02.025not published, 01 Mar 17ACUTE acute poisoning As DEATH Deaths Development EDUCATION Incidence India INDIUM MANAGEMENT method methods POISONING Population PROTOCOL Protocols Rural snake bite SNAKEBITE STUDY Time TREATMENT WHO 2/23/2017Snakebites cause death, disability and economic devastation to their victims, people who live almost exclusively in rural areas. Annually an estimated two million venomous bites cause as many as 100,000 deaths worldwide as well as hundreds of thousands of deformities and amputations. Recent studies suggest that India has the highest incidence of snakebite and associated deaths worldwide. In this study, we interviewed 25 hospital-based clinicians who regularly treat snakebites in Tamil Nadu, India, in order to gauge their opinions and views on the diagnostic tools and treatment methods available at that time, the difficulties encountered in treating snakebites and improvements to snakebite management protocols they deem necessary. Clinicians identified the improvement of community education, training of medical personnel, development of standard treatment protocols and improved medication as priorities for the immediate future121140/ field[33]: Not in File '?*Williams, J.H. Whitehead, Z. Van Wilpe, E.2016XParaquat intoxication and associated pathological findings in three dogs in South Africae1-e93Journal of the South African Veterinary Association871ABSORPTION ACCIDENTAL ACUTE Africa ANIMAL Animals ANTIDOTE Antidotes ANTIOXIDANT antioxidants As CELL cell death central nervous system CLINICAL Clinical presentation DEATH DIAGNOSIS DIURESIS dog DOGS DYSPNOEA ELIMINATION EXPERIMENTAL FAILURE FATAL FIBROSIS GASTROINTESTINAL Gastrointestinal absorption HAEMORRHAGE HOUSEHOLD HUMAN Humans INGESTION INTOXICATION IS LESIONS LUNG MANAGEMENT MEMBRANE OEDEMA PARAQUAT PROGNOSIS PULMONARY PULMONARY FIBROSIS RENAL RENAL FAILURE RESPIRATORY South Africa Toxicities TOXICITY TREATMENT Veterinary 11/9/2016Paraquat is a bipyridylium non-selective contact herbicide commonly used worldwide. When ingestion occurs by humans and animals either accidentally, intentionally or maliciously, paraquat selectively accumulates in the lungs resulting in the production of oxygen-free radicals, causing membrane damage and cell death. Intoxicated subjects typically show progressive and fatal pulmonary haemorrhage, collapse and oedema. In individuals surviving the acute phase, pulmonary fibrosis develops. Gastrointestinal-, renal- and central nervous system clinical signs may also occur. Owing to the lack of effective treatment and absence of an antidote, the prognosis is poor. The clinical presentation, clinicopathological findings and treatment are briefly described of three dogs from one South African household, intoxicated with paraquat. Macroscopic and microscopic lesions in one dog that was necropsied, as well as pulmonary ultrastructure are detailed and illustrated for academic reference. All dogs presented with tachypnoea and dyspnoea 2-3 days after accidental paraquat ingestion. Treatment was aimed at reducing gastrointestinal absorption, enhancing elimination by diuresis and avoiding further oxidative damage by administration of antioxidants. All dogs, however, became progressively hypoxic despite treatment and were euthanised. Paraquat toxicity should be a differential diagnosis in dogs with unexplained progressive respiratory and gastrointestinal signs and renal failure. The local veterinary profession should be aware of accidental or intentional paraquat toxicity of animals. Existing literature, variations possible in canine clinical signs, measured parameters, lesions, as well as possible treatments, promising experimental antidotes and management options are discussed120792+ field[33]: Not in File?%Windpessl, M. Schwarz, C. Wallner, M.2017"Bowel prep hyponatremia" – a state of acute water intoxication facilitated by low dietary solute intake: case report and literature review54BMC Nephrology181ACUTE ARGININE As case CASE REPORT Case-report Development DIETARY ENCEPHALOPATHY ENDOSCOPY hyponatremia ingested Intake INTOXICATION IS LEAD LITERATURE REVIEW ORAL PATHOPHYSIOLOGY PATIENT recovery Release REVIEW RISK Risk factor RISK FACTORS SODIUM TREATMENT VASOPRESSIN WATER WHO2/7/2017BACKGROUND: Symptomatic hyponatremia is considered a rare complication of oral bowel preparation for colonoscopy. The pathophysiology underlying this phenomenon has been widely regarded as a mere sequela of excessive arginine vasopressin (AVP) release. CASE PRESENTATION: This case describes a 61-year old woman who developed acute hyponatremic encephalopathy when preparing for elective outpatient lower endoscopy. She had had negligible oral solute intake for two days and ingested four liters of clear fluid within two hours. On admission, the patient was agitated and had slurred speech. Treatment with hypertonic saline lead to full recovery. A brisk aquaresis confirmed acute dilutional hyponatremia. CONCLUSION: Apart from elevated AVP-levels, the amount and speed of fluid intake and concomitant low-solute intake constitute important risk factors in the development of clinically relevant hyponatremias in patients undergoing colonoscopies. Understanding that the cause of sodium imbalance in this scenario is multifactorial and complex is pivotal to recognizing and ideally preventing this complication, for which we propose the term "bowel prep hyponatremia"120858+ field[33]: Not in FileNB?Wolff, V. Jouanjus, E.20176Strokes are possible complications of cannabinoids useEpilepsy and early: doi: 10.1016/j.yebeh.2017.01.031not published, 01 Mar 17ADULT Age ARTERIAL As Association BRAIN CANNABINOID cannabinoids CANNABIS CARDIOVASCULAR case CEREBRAL CHRONIC complications Consumption designer drug Development DISTRIBUTION DOE DRUG evidence EXPERIMENTAL experimental studies Frequency genetic HUMAN Humans Incidence IS Laboratories LABORATORY legalization MALE MECHANISM Mechanisms MITOCHONDRIA NO NOVEL PSYCHOACTIVE SUBSTANCES Occurrence OXIDATIVE STRESS OXYGEN PATIENT Population PROGNOSIS RESEARCH reversible RISK Risk factor SCREENING SEQUELAE Sex SPECIES STRESS STROKE STUDY SYNTHETIC CANNABINOID Synthetic cannabinoids TEMPORAL TEST TOBACCO Toxicities TOXICITY transient URINE use VASCULAR VASOCONSTRICTION Young Adult Young adults 2/23/2017 It is critically important to identify all factors that may play a role in the recent increase of the incidence of stroke among the young population. Considering the worldwide use of cannabinoids (cannabis and synthetic cannabinoids), the recent legalization of their consumption in some countries, and their supposed involvement in cardiovascular events, we evaluated their role in the occurrence of neurovascular complications among the young. Ninety-eight patients were described in the literature as having a cannabinoids-related stroke (85 after cannabis use and 13 after synthetic cannabinoids). The distribution by type of stroke was as follows: 4 patients with an undetermined type of stroke, 85 with an ischemic stroke and/or a transient ischemic attack, and 9 with a hemorrhagic stroke. The mean age of patients was 32.3+/-11.8years (range 15-63), and the majority of them were male with a sex ratio of 3.7:1. Cannabis was often smoked with tobacco in 66% of cases. Most of the patients with cannabinoids-related strokes were chronic cannabis users in 81% of cases, and for 18% of them, there was a recent increase of the amount of cannabis consumption during the days before the occurrence of stroke. Even if the prognosis of stroke was globally favorable in 46% of cases, with no or few sequelae, 5 patients died after the neurovascular event. One striking element reported in the majority of the reports was a temporal relationship between cannabinoids use, whether natural or synthetic, and the occurrence of stroke. However, a temporal correlation does not mean causation, and other factors may be involved. Cannabis may be considered as a risk factor of stroke until research shows evidence of an underlying mechanism that, alone or in association with others, contributes to the development of stroke. As of today, reversible cerebral vasoconstriction triggered by cannabinoids use may be a convincing mechanism of stroke in 27% of cases. Indeed, despite the widespread use of cannabinoids, the low frequency of neurovascular complications after their use may be due to a genetic predisposition to their neurovascular toxicity in some individuals. Further studies should focus on this point. More importantly however, this low frequency may be underestimated because the drug consumption may not be systematically researched, neither by questioning nor by laboratory screening. Besides this vascular role of cannabinoids in the occurrence of stroke, a cellular effect of cannabis on brain mitochondria was recently suggested in an experimental study. One of the mechanisms involved in young cannabis users with stroke may be the generation of reactive oxygen species leading to an oxidative stress, which is a known mechanism in stroke in humans. It is useful to inform the young population about the real potential risk of using cannabinoids. We suggest to systematically ask all young adults with stroke about their drug consumption including cannabinoids, to screen urine for cannabis or to include a specific diagnostic test to detect synthetic cannabinoids, and to obtain non-invasive intracranial arterial investigations (i.e. CT-angiography or cerebral MRA) in order to search for cerebral vasoconstriction. However, several questions remained unresolved and further research is still needed to assess the pathophysiological mechanisms involved in young cannabinoids users with stroke. This article is part of a Special Issue entitled "Cannabinoids and Epilepsy"120998- field[33]: Not in File B?'Wong, A. Sivilotti, M.L.A. Graudins, A.2017Accuracy of the paracetamol-aminotransferase multiplication product to predict hepatotoxicity in modified-release paracetamol overdoseClinical Toxicology0online early: doi: 10.1080/15563650.2017.1290253not published, 03 Mar 17acetylcysteine ACUTE ALANINE As baseline Cohort Cohort studies Cohort study Cut-off Development EXPOSURE formulation HEPATOTOXICITY HOSPITAL INGESTION injuries Injury IS LIVER liver injury NO OVERDOSE PARACETAMOL PATIENT RISK self-report Sensitivity STUDY TEMPORAL Testing Time WHO 2/15/2017 Context: The paracetamol-aminotransferase multiplication product (APAP x ALT) is a risk predictor of hepatotoxicity that is somewhat independent of time and type of ingestion. However, its accuracy following ingestion of modified-release formulations is not known, as the product has been derived and validated after immediate-release paracetamol overdoses.Objective: The aim of this retrospective cohort study was to evaluate the accuracy of the multiplication product to predict hepatotoxicity in a cohort of patients with modified-release paracetamol overdose.Methods: We assessed all patients with modified-release paracetamol overdose presenting to our hospital network from October 2009 to July 2016. Ingestion of a modified-release formulation was identified by patient self-report or retrieval of the original container. Hepatotoxicity was defined as peak alanine aminotransferase ³1000 IU/L, and acute liver injury (ALI) as a doubling of baseline ALT to more than 50 IU/L.Results: Of 1989 paracetamol overdose presentations, we identified 73 modified-release paracetamol exposures treated with acetylcysteine. Five patients developed hepatotoxicity, including one who received acetylcysteine within eight hours of an acute ingestion. No patient with an initial multiplication product <10,000 mg/L x IU/L developed hepatotoxicity (sensitivity 100% [95%CI 48%, 100%], specificity 97% [90%, 100%]). Specificity fell to 54% (95%CI: 34, 59%) at a product cut-off point <1500 mg/L x IU/L. When calculated within eight hours of ingestion, mild elevations of the multiplication product fell quickly on repeat testing in patients without ALI or hepatotoxicity.Conclusions: In modified-release paracetamol overdose treated with acetylcysteine, the paracetamol-aminotransferase multiplication product demonstrated similar accuracy and temporal profile to previous reports involving mostly immediate-release formulations. Above a cut-point of 10,000 mg/L x IU/L, it was very strongly associated with the development of acute liver injury and hepatotoxicity, especially when calculated more than eight hours post-ingestion. When below 1500 mg/L x IU/L the likelihood of developing hepatotoxicity was very low. Persistently high serial multiplication product calculations were associated with the greatest risk of hepatotoxicity121149/ field[33]: Not in File L?-Wong, L.L. Lacar, L. Roytman, M. Orloff, S.L.2017QUrgent liver transplantation for dietary supplements: an under-recognized problem322-325Transplantation Proceedings492ACETAMINOPHEN ACUTE acute liver failure ADULT Age agent As case DIETARY Dietary supplement Dietary supplements DRUG drug induced liver injury drug-induced Drug-induced liver injury Emergencies emergency EVALUATION FAILURE HD HEPATIC HEPATIC NECROSIS HEPATOTOXICITY HERBAL MEDICINE injuries Injury IS LEAD LIVER Liver failure liver injury Liver Transplantation Medicine medicines method methods NECROSIS outbreak PATIENT Registry STUDY Toxicities TOXICITY TRANSPLANT UNITED STATES use WHO3/2017dBACKGROUND: The recent outbreak of acute liver failure caused by herbal/dietary supplements (HDS) in Hawaii prompted evaluation of those patients who underwent emergency liver transplantation (LT) for HDS in the United States. METHODS: We queried the Scientific Registry of Transplant Recipients (2003-2015) to identify patients who underwent urgent LT for acute hepatic necrosis (AHN) and identified those with HDS use. This group of patients was then characterized. RESULTS: Of 2408 adult cases, 625 were characterized as a drug-induced liver injury. The majority of cases (n = 300) were due to acetaminophen toxicity, but the fourth highest category was due to HDS (n = 21). Of these 21 cases caused by HDS, 13 did not list the specific agent responsible, mean age was 36 years, and all cases occurred after 2007. There probably are more cases because 25% of all LT cases in the study did not list a specific reason for liver failure and 20% of all drug-induced liver failure did not list a specific drug. CONCLUSIONS: Herbal/supplement use is the fourth most common cause of drug-induced AHN requiring LT, albeit an underestimation of the problem. Detailed questioning of patients and their support systems regarding herbal/supplement use and better reporting are imperative to further define this problem and identify products that have the potential to lead to liver failure1211424 field[33]: Not in File?Wu, P.-Y. Cheng, C.-Y. Liu, C.-E. Lee, Y.-C. Yang, C.-J. Tsai, M.-S. Cheng, S.-H. Lin, S.-P. Lin, D.-Y. Wang, N.-C. Lee, Y.-C. Sun, H.-Y. Tang, H.-J. Hung, C.-C.2017Multicenter study of skin rashes and hepatotoxicity in antiretroviral-naïve HIV-positive patients receiving non-nucleoside reverse-transcriptase inhibitor plus nucleoside reverse-transcriptase inhibitors in Taiwane0171596PLoS ONE122ADULT Adverse adverse event Adverse events AIDS analysis ANTIBODIES antiretroviral therapy ANTIVIRAL baseline CELL CLINICAL DATA DERMAL Development DRUG drugs EFAVIRENZ Guidelines HEPATITIS HEPATITIS C HEPATOTOXICITY HIV HOSPITAL Incidence Laboratories LABORATORY method methods NEVIRAPINE Odds Ratio PATIENT PLASMA RASH Regression Analysis reverse transcriptase inhibitors RISK SCALE SKIN STUDY Taiwan THERAPY Toxicities TOXICITY TREATMENT use2017t OBJECTIVES: Two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) plus 1 non-NRTI (nNRTI) remain the preferred or alternative combination antiretroviral therapy (cART) for antiretroviral-naive HIV-positive patients in Taiwan. The three most commonly used nNRTIs are nevirapine (NVP), efavirenz (EFV) and rilpivirine (RPV). This study aimed to determine the incidences of hepatotoxicity and skin rashes within 4 weeks of initiation of cART containing 1 nNRTI plus 2 NRTIs. METHODS: Between June, 2012 and November, 2015, all antiretroviral-naive HIV-positive adult patients initiating nNRTI-containing cART at 8 designated hospitals for HIV care were included in this retrospective observational study. According to the national HIV treatment guidelines, patients were assessed at baseline, 2 and 4 weeks of cART initiation, and subsequently every 8 to 12 weeks. Plasma HIV RNA load, CD4 cell count and aminotransferases were determined. The toxicity grading scale of the Division of AIDS (DAIDS) 2014 was used for reporting clinical and laboratory adverse events. RESULTS: During the 3.5-year study period, 2,341 patients initiated nNRTI-containing cART: NVP in 629 patients, EFV 1,363 patients, and RPV 349 patients. Rash of any grade occurred in 14.1% (n = 331) of the patients. In multiple logistic regression analysis, baseline CD4 cell counts (per 100-cell/mul increase, adjusted odds ratio [AOR], 1.125; 95% confidence interval [95% CI], 1.031-1.228) and use of NVP (AOR, 2.443; 95% CI, 1.816-3.286) (compared with efavirenz) were independently associated with the development of skin rashes. Among the 1,455 patients (62.2%) with aminotransferase data both at baseline and week 4, 72 (4.9%) developed grade 2 or greater hepatotoxicity. In multiple logistic regression analysis, presence of antibody for hepatitis C virus (HCV) (AOR, 2.865; 95% CI, 1.439-5.704) or hepatitis B surface antigen (AOR, 2.397; 95% CI, 1.150-4.997), and development of skin rashes (AOR, 2.811; 95% CI, 1.051-7.521) were independently associated with the development of hepatotoxicity. CONCLUSIONS: The baseline CD4 cell counts and use of NVP were associated with increased risk of skin rashes, while hepatotoxicity was independently associated with HCV or hepatitis B virus coinfection, and development of skin rashes in antiretroviral-naive HIV-positive Taiwanese patients within 4 weeks of initiation of nNRTI-containing regimens121093. field[33]: Not in FileB?DWulz, J.L. Sung, H. Dugan, B.D. Wensel, T.M. Lander, R. Manzella, B.2017gThe pharmacist role in the development and implementation of a naloxone prescription program in Alabama/Journal of the American Pharmacists Association-online early: doi: 10.1016/j.japh.2016.12.078not published, 01 Mar 17arm DEATH Deaths Development EDUCATION EPIDEMIC EVALUATION family HEALTH HEROIN IS NALOXONE OPIOID Opioids PRESCRIBING PROTOCOL PUBLIC SERVICE WHO 2/10/2017OBJECTIVE: The purpose of this report is to describe the development and implementation of a pharmacist-led naloxone-training and prescription service at a county health department. SETTING: Jefferson County Department of Health, Birmingham, Alabama. PRACTICE DESCRIPTION: This service was developed in response to the overwhelming heroin and opioid epidemic that is currently affecting the entire nation and which is highly prevalent in the state of Alabama. Because of this epidemic, new state laws have been established regarding prescriptive authority, liability, and possession of naloxone. PRACTICE INNOVATION: Through a collaborative protocol, pharmacists at the Jefferson County Department of Health were responsible for prescribing and educating the public about naloxone. EVALUATION: Between 2014 and 2015 the Jefferson County Coroner reported a 131% increase in opioid prescription-related deaths indicating the continued need for the naloxone prescription program. RESULTS: In total, 83 clients were trained and 150 naloxone kits were distributed among heroin and opioid users, concerned family members or friends, and those who work closely with users. CONCLUSION: This service and its extending arms were developed in response to the need for naloxone education among heroin and opioid users, their family members, civil servants who work with users, and family practice physicians who prescribe opioids121033, field[33]: Not in File)?1Xiao, J. Lamba, P. Chan, C. Cardasis, W. Jain, A.2014PHyperammonemia caused by valproate; this common side effect needs more attention78-79 CNS Spectrums201ABSORPTION ABSTRACT AMMONIA ANIMAL animal models Antiepileptic As Attention Awareness baseline Benzodiazepine BENZODIAZEPINES case CASE REPORT Case-report CHRONIC chronic pain CLINICAL cognitive Cognitive function CONCENTRATIONS dependence DEPRESSION DETOXIFICATION DOSAGE DRUG DULOXETINE EEG ENCEPHALOPATHY FEMALE Frequency Guidelines GUT HEALTH HEPATIC history HOSPITAL Hyperammonemia IMPAIRMENT IS Knowledge Laboratories LABORATORY LIVER LIVER FUNCTION Mental health MODEL MONITORING MOOD motor mu NO pain PATIENT PHENOBARBITAL PHENYTOIN PSYCHIATRIC QUETIAPINE RISK Risk factor RISK FACTORS seizure SERUM Side effect STUDY TEST Testing THERAPEUTIC THERAPY TREATMENT UNIT use VALPROATE Vomiting2014120762+ field[33]: Not in Filey?9Xiao, W.-L. Liu, X.-Y. Liu, Y.-S. Zhang, D.-Z. Xue, L.-F.2017YThe relationship between maternal corticosteroid use and orofacial clefts-a meta-analysis99-105Reproductive Toxicology69analysis Association case-control case-control study Cohort Cohort studies Cohort study CORTICOSTEROIDS DEVELOPMENTAL DISEASE dose EXPOSURE FOLLOW UP Follow-up IS Meta-analysis oc Occurrence PREGNANCY PRENATAL Prenatal exposure RISK Route STUDY use 2/13/2017vThe aim was to evaluate the relationship between maternal corticosteroid use during first trimester of pregnancy and risk of orofacial clefts (OC). The overall findings showed a certain association between maternal corticosteroid use and occurrence of OC, compared with non-users (OR=1.16 [95% CI: 1.01-1.33]). When study type was considered this association was significant only for case-control studies (OR=1.22 [95% CI: 1.02-1.47]), and not for cohort studies (OR=1.09 [95% CI: 0.88-1.34]) when there are many confounders (dose, route of application, disease etc.) and biases (re-call, loss-to follow-up etc.) that still need to be considered. A subgroup analysis based on the type of OC gave an overall OR of 1.41 (95% CI: 1.14-1.74) in the case-control studies for cleft lip with or without palate (CL/P) and 1.09 (95% CI: 0.80-1.48) for cleft palate only (CPO), when comparing maternal corticosteroid users with non-users. However, for cohort studies, the overall OR for CL/P is 1.06 (95% CI: 0.82-1.37) and 1.20 (95% CI: 0.83-1.75) for CPO. The absolute risk of facial cleft after prenatal exposure to corticosteroids, if any, is small1211060 field[33]: Not in File ?Xie, Y. Zhou, G.2017oEffects of meso-2,3-dimercaptosuccinic acid, potassium iodide and chlorophyll on lead accumulation in male mice87-93<International Journal of Occupational & Environmental Health301eABSORPTION ACETATE ACID As Atomic absorption spectrometry BLOOD COMPARISON CONCENTRATIONS DMSA evidence EXPERIMENTAL EXPOSURE FOOD HEALTH IN VIVO IS KIDNEY LEAD Lead acetate Lead Poisoning LIVER MALE MESO-2,3-DIMERCAPTOSUCCINIC ACID method methods MICE PbAc POISONING POLLUTION POTASSIUM preventive measures PUBLIC PUBLIC HEALTH SPECTROMETRY STUDY TREATMENT 2/21/2017OBJECTIVES: Lead (Pb) pollution is a serious public health problem all over the world, it especially plays severe damage role in children's health. Apart from reducing lead-induced damages, the decrease of lead accumulation is also critical. This study has been the first attempt to investigate effects of meso-2,3-dimercaptosuccinic acid (DMSA), potassium iodide (KI) and chlorophyll (Chl) on lead accumulation in male mice. MATERIAL AND METHODS: Eighty healthy Kunming male mice were selected and divided randomly into 8 groups. They were treated with lead acetate (PbAc) intraperitoneally, individually and in combination with the DMSA, KI or Chl once daily for 5 days. Meanwhile, the control group was treated with normal saline during the whole exposure period. On 30th day, mice were sacrificed and lead concentrations were detected in the whole blood, livers, kidneys, and testicles of mice by means of the graphite furnace atomic absorption spectrometry. RESULTS: In comparison with the control group, lead concentrations increased in mice treated with the PbAc and DMSA, KI and Chl diminished lead accumulation in the whole blood, livers, and kidneys. Chl had specifically the same effects on lead concentrations in the testicles of male mice. CONCLUSIONS: Potassium iodide and Chl, as food additives, had the same effects as the DMSA to reduce lead accumulation in male mice effectively. Our results provided experimental evidence in vivo for the preventive measures of lead poisoning. Int J Occup Med Environ Health 2017;30(1):87-93121028* field[33]:,61370,0,2.html Not in File 9B?Xu, Y. Schulman, S. Dowlatshahi, D. Holbrook, A.M. Simpson, C.S. Shepherd, L.E. Wells, P.S. Giulivi, A. Gomes, T. Mamdani, M. Khuu, W. Frymire, E. Johnson, A.P.2017Direct oral anticoagulant- or warfarin-related major bleeding: characteristics, reversal strategies and outcomes from a multi-center observational early: doi: 10.1016/j.chest.2017.02.009not published, 01 Mar 17hACUTE acute poisoning agent ANTICOAGULANT anticoagulants Association baseline BLOOD Canada case CELL CLINICAL Cohort DATABASE EVALUATION hemorrhage HOSPITAL method methods MORTALITY ORAL outcome PATIENT POISONING prothrombin complex concentrate REACH RISK SAFETY STUDY TERTIARY CARE THERAPY transfusion TREATMENT TRIAL UNIT UNITS use vitamin VITAMIN K WARFARIN 2/17/2017BACKGROUND: Direct oral anticoagulants (DOACs) have expanded the armamentarium for antithrombotic therapy. While DOAC-related major bleeds were associated with favourable outcomes compared to warfarin in clinical trials, warfarin was reversed in <40% of cases, raising concerns about the generalizability of this finding. METHODS: Consecutive patients >/=66 years presenting to five tertiary care hospitals across three cities in Ontario, Canada with diagnoses that included hemorrhage from October 2010 to March 2015. Charts were screened for association with DOAC or warfarin use; eligible cases were abstracted and linked to administrative databases. RESULTS: Among 19,061 records screened, 2,002 (460 DOAC, 1542 warfarin) were eligible. Reversal agents were frequently used among warfarin bleeds (72.9% vitamin K, 40.7% prothrombin complex concentrates). Red blood cell transfusions occurred more often among DOAC bleeds than warfarin (52.0% vs. 39.5%, adjusted relative risk [aRR] 1.32 [95% CI 1.19 - 2.47]). However, units of blood products transfused were not different between the two groups. Thirty-four DOAC cases (7.4%) received activated prothrombin complex concentrates or recombinant factor VIIa. In-hospital mortality was lower following DOAC bleeding (9.8% vs. 15.2%, aRR 0.66 [95% CI 0.49 - 0.89], although differences in 30-day mortality did not reach statistical significance (12.6% vs. 16.3%, aRR 0.79 [95% CI 0.61 - 1.03]). CONCLUSIONS: In this unselected cohort of patients with oral anticoagulant-related hemorrhage with high rates of warfarin reversal, in-hospital mortality was lower among DOAC-associated bleeds. These findings support the safety of DOACs in routine care and present useful baseline measures for evaluations of DOAC-specific reversal agents120967- field[33]: Not in File '?"Yanagiha, K. Ishii, K. Tamaoka, A.2017Acetylcholinesterase inhibitor treatment alleviated cognitive impairment caused by delayed encephalopathy due to carbon monoxide poisoning: Two case reports and a review of the literaturee6125Medicine (Baltimore)968ACETYLCHOLINE ACETYLCHOLINE RECEPTOR ACETYLCHOLINESTERASE ACUTE Aged BRAIN carbon CARBON MONOXIDE carbon monoxide poisoning case CASE REPORT case reports Case-report CO cognitive cognitive dysfunction Cognitive function CONCENTRATIONS DEMENTIA ENCEPHALOPATHY GALANTAMINE Hippocampus HYPERBARIC OXYGEN hyperbaric oxygen therapy Imaging IMPAIRMENT LESIONS LEVELS MAGNETIC RESONANCE magnetic resonance imaging outcome OXYGEN PATIENT POISONING REVIEW SCALE SYMPTOMS THERAPY Toxicities TOXICITY TREATMENT WOMEN2/2017INTRODUCTION: Delayed encephalopathy due to carbon monoxide (CO) poisoning can even occur in patients with mild symptoms of acute CO poisoning. Some cases taking conventional hyperbaric oxygen (HBO) therapy or steroid-pulse therapy may be insufficient, and AchEI may be effective. PATIENT CONCERNS AND DIAGNOSES: We report two cases of delayed encephalopathy after acute CO poisoning involving two women aged 69 (Case 1) and 60 years (Case 2) whose cognitive function improved with acetylcholinesterase inhibitor (AchEI) treatment. Delayed encephalopathy occurred 25 and 35 days after acute CO poisoning in Case 1 and Case 2, respectively. Both patients demonstrated cognitive impairment, apathy, and hypokinesia on admission. INTERVENTIONS AND OUTCOMES: Although hyperbaric oxygen therapy did not yield any significant improvements, cognitive dysfunction improved substantially. This was evidenced by an improved Mini-Mental State Examination score ffom 9 to 28 points in Case 1 and an improved Hasegawa's dementia rating scale score from 4 to 25 points in Case 2 after administration of an AchEI. In Case 1, we administered galantamine hydrobromide, which was related with improved white matter lesions initially detected on brain magnetic resonance imaging. However, in Case 2 white matter lesions persisted despite AchEI treatment. AchEI treatment may result in improved cognitive and frontal lobe function by increasing low acetylcholine concentrations in the hippocampus and frontal lobe caused by decreased nicotinic acetylcholine receptor levels in delayed encephalopathy after CO poisoning. CONCLUSION: Physicians should consider AchEIs for patients demonstrating delayed encephalopathy due to CO poisoning121070- field[33]: Not in File 2?Yang, W.-Y. Zhang, Z.-Y. Thijs, L. Cauwenberghs, N. Wei, F.-F. Jacobs, L. Luttun, A. Verhamme, P. Kuznetsova, T. Nawrot, T.S. Staessen, J.A.2017aLeft ventricular structure and function in relation to environmental exposure to lead and cadmiume004692)Journal of the American Heart Association629Age As ASSESSMENT Association BLOOD Blood lead CADMIUM CARDIOTOXICITY ENVIRONMENTAL Environmental exposure EXPERIMENTAL experimental studies EXPOSURE FAILURE HEART heart failure HUMAN Imaging LEAD Longitudinal method methods MODEL MYOCARDIUM Population RISK Risk factor STUDY toxic toxic effects urinary use WOMEN2/1/2017BACKGROUND: Experimental studies have demonstrated that lead and cadmium have direct toxic effects on the myocardium, but the few human studies are limited by design, assessment of exposure, and use of heart failure as a late-stage endpoint. METHODS AND RESULTS: In a prospective population study, we studied the association of left ventricular (LV) function with blood lead (BPb) and 24-hour urinary cadmium (UCd). In 179 participants randomly recruited from a Flemish population (50.3% women; mean age 39.1 years), geometric mean BPb and UCd at enrollment (1985-2000) were 0.20 mumol/L and 6.1 nmol, respectively. We assessed systolic and diastolic LV function 11.9 years (median) later (2005-2010) by using Doppler imaging of the transmitral blood flow and the mitral annular movement and speckle tracking. In multivariable-adjusted linear regression, LV systolic function decreased with BPb. For a doubling of exposure, estimates were -0.392% for global longitudinal strain (P=0.034), -0.618% and -0.113 s-1 for regional longitudinal strain (P=0.028) and strain rate (P=0.008), and -0.056 s-1 for regional radial strain rate (P=0.050). Regional longitudinal strain rate (-0.066 s-1, P=0.009) and regional radial strain (-2.848%, P=0.015) also decreased with UCd. Models including both exposure indexes did not allow differentiating whether LV dysfunction was predominately related to BPb or UCd. Diastolic LV function was not associated with BPb or UCd (P>/=0.159). CONCLUSIONS: Although effect sizes were small, our results suggest that environmental exposure to lead, cadmium, or both might be a risk factor for systolic LV dysfunction, a condition often proceeding to heart failure120779) field[33]: Not in File 3B?*Yang, Y. Chen, W. Wang, M. Li, Y. Peng, C.2017uEvaluating the potential health risk of toxic trace elements in vegetables: accounting for variations in soil factors Science of the Total Environment2online early: doi: 10.1016/j.scitotenv.2017.01.143not published, 28 Feb 17gADULT AGRICULTURAL ARSENIC ASSESSMENT CADMIUM Cd China CONCENTRATIONS Consumption CONTAMINATION Content DIETARY Dietary exposure edible ENVIRONMENTAL EXPOSURE hazardous HEALTH Health risk Intake INTERACTION IS LEAD MERCURY MODEL pH PLANT Population Potential health risk RISK RISK ASSESSMENT safe SOIL Source SPECIES SURVEY toxic Trace elements use Vegetables2/6/2017iVegetable crop consumption is one of the main sources of dietary exposure to toxic trace elements (TEs). A paired survey of soil and vegetable samples was conducted in 589 agricultural sites in the Youxian prefecture, southern China, to investigate the effect of soil factors on the accumulation of arsenic, cadmium, mercury, and lead in different vegetables. A site-specific model was developed to estimate the health risk from vegetable consumption. The TE concentration varied in different plant species, and rape can be cultivated in contaminated areas for its potential use in restricting the transfer of TE from soil to edible plant parts. The accumulation of TEs in vegetables was governed by multiple factors, mainly element interaction, metal availability (extractable CaCl2 fraction), and soil pH. Soil Zn may promote Cd accumulation in vegetables when soil Cd/Zn ratio>0.02. Cadmium is a major hazardous component. About 80.8% of the adult populations consuming locally produced vegetables had a daily Cd intake risk above the safe standard. Among investigated vegetables, radish is potentially hazardous for populations because of its high consumption rate and high Cd content but low Zn accumulation. The consumption of radish cultivated in highly acidic soil (4>Yarema, M.C. Sivilotti, M.L.A. Nettel-Aguirre, A. Rumack, B.H.2017Reply to: Limitations of the evidence supporting use of undetectable acetaminophen levels obtained <4 hours post-ingestion to rule out toxicityClinical Toxicology0online early: doi: 10.1080/15563650.2017.1287914not published, 03 Mar 17NACETAMINOPHEN evidence LETTER LEVELS PARACETAMOL reply Toxicities TOXICITY use2/9/2017121160/ field[33]: Not in File?jYarmohammadi, H. Hamidvand, E. Abdollahzadeh, D. Sohrabi, Y. Poursadeghiyan, M. Biglari, H. Ebrahimi, M.H.2016hMeasuring concentration of welding fumes in respiratory zones of welders: an ergo-toxicological approach111-115$Research Journal of Medical Sciences103As DATA EXPOSURE FUMES HEALTH INHALATION IS MET OCCUPATIONAL RESEARCH RESPIRATORY SAFETY standards STUDY VENTILATION Welders welding WELDING FUMES workers2016Welding is a critical and important operation in various industries. The operation produces poisonous fumes and gases that can cause respiratory problems towelding technicians. National Institute of Occupational Safety and Health estimates that at least 2 million workers arerecruited as welders. This makes it necessary to preserve and protect the well-being of researchers by measuring the level of fumes inhaled by researchers. A descriptive-cross sectional study was carried out in welding workshops within the Nahav and Hamadan City of Iran. In order to measure the density of welding fumes in respiratory spaces, NIOSH 7300 and 7048 were followed. The collected data were compared with NIOSH and ACGIH standards and the results were presentedin tables and diagrams. As shown by the results, out of 15 specimens taken from the respiratory system of subjects, 3 (20%) met the standards and 12 (80%) exceeded the standards. This result indicated an imperative need to find alternative processes, provide ventilation systems for research shops and welding spots, equip the workers with respiratory masks, carry out routine check-ups so that their exposure to welding fumes can be reduced. Copyright © Medwell Journals, 2016120836- field[33]: Not in FileC? Yates, D.2017Glia: a toxic reaction130Nature Reviews: Neuroscience18astrocytes author BRAIN CELL CNS DEATH DISEASE ENDOTOXIN GENE EXPRESSION Glia injuries Injury IS Lipopolysaccharide microglia NEUROLOGICAL neuron recovery STUDY toxic Toxic reaction2/2/2017120798% field[33]: Not in FileO?,Yu, J.-H. Chen, D.-Y. Chen, H.-Y. Lee, K.-H.2016eIntravenous lipid-emulsion therapy in a patient with cardiac arrest after overdose of diphenhydramine 1017-1018+Journal of the Formosan Medical Association11511ANIMAL ANTICHOLINERGIC ARREST CARDIAC CARDIAC ARREST CARDIOTOXICITY DIPHENHYDRAMINE HUMAN Humans INGESTION INTRAVENOUS IS LIPID Lipid emulsion LIPID EMULSION THERAPY OVERDOSE PATIENT THERAPY2016tDiphenhydramine overdose is characterized mostly by sedative and anticholinergic effects. Cardiotoxicity and circulatory collapse after massive ingestion of diphenhydramine have rarely been reported.1 Positive effects of intravenous lipid-emulsion (ILE) therapy for diphenhydramine overdose were reported in an animal study,2 although its role in humans remains uncertain.120791, field[33]: Not in File"?Yudelowitz, G.2017)Intentional intravenous mercury injection112-114South African Medical Journal1072Adverse As bipolar case CASE REPORT Case-report CLINICAL complications ILLNESS INGESTION INHALATION INJECTION INTRAVENOUS INTRAVENOUS INJECTION IS Man MERCURY ORAL SEQUELAE Toxicities TOXICITY TREATMENT VAPOUR WHO 1/30/2017Mercury toxicity is commonly associated with vapour inhalation or oral ingestion, for which there exist definite treatment options.Intravenous mercury injection is rarely seen, with few documented cases. Treatment strategies are not clearly defined for such cases,although a few options do show benefit. This case report describes a 29-year-old man suffering from bipolar disorder, who presentedfollowing self-inflicted intravenous injection of mercury. Clinical and radiographic features, possible adverse clinical sequelae in preexistingmental illness and further complications are discussed, as well as possible treatment strategies in light of relevant literature1211160 field[33]: Not in File B?"Zabbey, N. Sam, K. Onyebuchi, A.T.2017WRemediation of contaminated lands in the Niger Delta, Nigeria: prospects and challenges Science of the Total Environment2online early: doi: 10.1016/j.scitotenv.2017.02.075not published, 01 Mar 17(AIR As ASSESSMENT Attention burden case case studies Case Study CLAY CONTAMINATION effectiveness Environment ENVIRONMENTAL GA GAS hazardous HAZARDOUS WASTE impact IS Nigeria NO OIL PAPER POLLUTION Population Regulatory Release REMEDIATION SOCIAL SOIL standards STUDY Toxicities TOXICITY use WATER 2/14/2017xContamination of the total environment (air, soil, water and biota) by crude oil has become a paramount interest in the Niger Delta region of Nigeria. Studies have revealed variable impacts of oil toxicity on the environment and exposed populations. The revelation gained much international attention in 2011 with the release of Environmental Assessment of Ogoniland report by the United Nations Environment Programme (UNEP). This has up scaled local and international pressures for urgent clean-up and restoration of degraded bio-resource rich environments of the Niger Delta, starting from Ogoniland. Previous remediation attempts in the area had failed due to erroneous operational conclusions (such as conclusions by oil industry operators that the Niger Delta soil is covered by a layer of clay and as such oil percolation remains within the top soil and makes remediation by enhanced natural attenuation (RENA) suitable for the region) and the adoption of incompatible and ineffective approaches (i.e. RENA) for the complex and dynamic environments. Perennial conflicts, poor regulatory oversights and incoherent standards are also challenges. Following UNEP recommendations, the Federal Government of Nigeria recently commissioned the clean-up and remediation of Ogoniland project; it would be novel and trend setting. While UNEP outlined some measures of contaminated land remediation, no specific approach was identified to be most effective for the Niger Delta region. Resolving the technical dilemma and identified social impediments is the key success driver of the above project. In this paper, we reviewed the socio-economic and ecological impacts of contaminated land in the Niger Delta region and the global state-of-the-art remediation approaches. We use coastal environment clean-up case studies to demonstrate the effectiveness of bioremediation (sometimes in combination with other technologies) for remediating most of the polluted sites in the Niger Delta. Bioremediation should primarily be the preferred option considering its low greenhouse gas and environmental footprints, and low-cost burden on the weak and overstretched economy of Nigeria1211141 field[33]: Not in FileB?"Zamani, N. Hassanian-Moghaddam, H.2017UIntravenous buprenorphine: a substitute for naloxone in methadone-overdosed patients?Annals of Emergency Medicine4online early: doi: 10.1016/j.annemergmed.2016.12.024not published, 01 Mar 17 ACUTE agent ANTIDOTE BUPRENORPHINE complications DEPRESSION INFARCTION INTRAVENOUS IS Man METHADONE MYOCARDIAL INFARCTION NALOXONE OPIOID PATIENT RESPIRATORY RESPIRATORY DEPRESSION respiratory distress safe Signs and symptoms SYMPTOMS Syndrome TREATMENT WHO WITHDRAWAL 2/23/2017Administration of naloxone is a common treatment for opioid-dependent patients who present with respiratory depression. Although safe in opioid-naive patients, naloxone may cause severe and even life-threatening complications in opioid-dependent patients, including acute respiratory distress syndrome and myocardial infarction. It has been suggested that administration of buprenorphine, a partial mu-opioid receptor agonist, to an opioid-intoxicated patient may result in reversal of respiratory depression with less severe withdrawal signs and symptoms. In addition, the longer half-life of buprenorphine compared with naloxone may reduce the need for repetitive administration of antidote. We present a 20-year-old morphine-addicted man who presented with methadone-induced respiratory depression and responded safely and effectively to intravenous administration of buprenorphine. Buprenorphine may be a useful alternative opioid reversal agent for opioid-dependent patients1209453 field[33]: Not in File B?FZeeshan, M. Murugadas, A. Ghaskadbi, S. Ramaswamy, B.R. Akbarsha, M.A.2017Ecotoxicological assessment of cobalt using Hydra model: ROS, oxidative stress, DNA damage, cell cycle arrest, and apoptosis as mechanisms of toxicityEnvironmental Pollution/online early: doi: 10.1016/j.envpol.2016.12.042not published, 01 Mar 17ganalysis ANTIOXIDANT apoptosis ARREST As ASSAY ASSESSMENT Bax biological CELL COBALT Comet assay DATA DEVELOPMENTAL DNA DNA DAMAGE dose EXPOSURE G6PD Heavy metal HISTOLOGY INDUCTION MECHANISM mechanism of action Mechanisms MODEL OXIDATIVE STRESS POLLUTION PROTEIN proteins REPRODUCTION RISK RISK ASSESSMENT ROS SPECIES STRESS Toxicities TOXICITY TREATMENT use 2/17/2017{The mechanisms underlying cobalt toxicity in aquatic species in general and cnidarians in particular remain poorly understood. Herein we investigated cobalt toxicity in a Hydra model from morphological, histological, developmental, and molecular biological perspectives. Hydra, exposed to cobalt (0-60 mg/L), were altered in morphology, histology, and regeneration. Exposure to standardized sublethal doses of cobalt impaired feeding by affecting nematocytes, which in turn affected reproduction. At the cellular level, excessive ROS generation, as the principal mechanism of action, primarily occurred in the lysosomes, which was accompanied by the upregulation of expression of the antioxidant genes SOD, GST, GPx, and G6PD. The number of Hsp70 and FoxO transcripts also increased. Interestingly, the upregulations were higher in the 24-h than in the 48-h time-point group, indicating that ROS overwhelmed the cellular defense mechanisms at the latter time-point. Comet assay revealed DNA damage. Cell cycle analysis indicated the induction of apoptosis accompanied or not by cell cycle arrest. Immunoblot analyses revealed that cobalt treatment triggered mitochondria-mediated apoptosis as inferred from the modulation of the key proteins Bax, Bcl-2, and caspase-3. From this data, we suggest the use of Hydra as a model organism for the risk assessment of heavy metal pollution in aquatic ecosystems120985. field[33]: Not in File B?Zepeda-Arce, R. Rojas-Garcia, A.E. Benitez-Trinidad, A. Herrera-Moreno, J.F. Medina-Díaz, I.M. Barrón-Vivanco, B.S. Villegas, G.P. Hernández-Ochoa, I. Sólis Heredia, M.J. Bernal-Hernández, Y.Y.2017pOxidative stress and genetic damage among workers exposed primarily to organophosphate and pyrethroid pesticidesEnvironmental Toxicology$online early: doi: 10.1002/tox.22398not published, 01 Mar 17Agriculture ANTIOXIDANT antioxidant enzymes As ASSAY CAT CATALASE Comet assay determination DNA DNA DAMAGE ENZYME EXPOSURE genetic genotoxic GLUTATHIONE HEALTH LEVELS Long term Long-term MDA MECHANISM Mechanisms OCCUPATIONAL OCCUPATIONAL EXPOSURE op organophosphate Organophosphates outcome OXIDATIVE STRESS P pesticide PESTICIDES PUBLIC PUBLIC HEALTH py PYRETHROID Pyrethroids STRESS STUDY SUPEROXIDE SUPEROXIDE DISMUTASE use workers 2/24/2017The indiscriminate use of pesticides in agriculture and public health campaigns has been associated with an increase of oxidative stress and DNA damage, resulting in health outcomes. Some defense mechanisms against free radical-induced oxidative damage include the antioxidant enzyme systems. The aim of this study was to determine the levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and the relationship of antioxidant enzyme levels with DNA damage among sprayers (workers) occupationally exposed to pesticides. The determinations of MDA and antioxidant enzymes were performed spectrophotometrically. The genotoxic effects were evaluated using the comet assay. The results showed a marginally significant decrease in SOD and CAT activities in the high exposure group compared to the control group. For MDA, statistically significant differences were found among people working long term vs. those working temporarily (P = 0.02) as sprayers. In the moderate exposure group, a positive correlation was observed between MDA levels and GPx activity. In the high exposure group, a negative correlation was observed between GR and CAT activities, and between MDA levels and GPx activities. Furthermore, in the high exposure group, a positive correlation between DNA damage parameters and MDA levels was observed. The results suggest an important role of antioxidant enzymes for the protection of DNA damage caused by occupational exposure to pesticides120989# field[33]: Not in File N?3Zhang, B. Li, M. Zhou, S. Dai, X. Xiong, P. Zhu, S.2016[A dental fluorosis trend analysis of children aged 8 to 12 in drinking-water-type endemic fluorosis areas of Hubei Province from 2010 to 2014]664-667Chinese Journal of Endemiology359Aged analysis As CHILDREN Content DENTAL DRINKING WATER EPIDEMIC Fixed FLUORIDE FLUORINE IS method methods MONITORING P PAEDIATRIC prevalence preventive measures quality SURVEILLANCE trends WATER2016Objective Through the dynamical monitoring of the water improvement projects operation, we intend to understand the prevalent trends of endemic fluorosis of children aged 8 to 12 in Hubei, to evaluate the effect of control measures antl to provide the basis for making preventive measures. Methods In Hubei, ten surveillance counties were selected, and three epidemic villages were selected as fixed monitoring villages in each county from 2010 to 2014. In those villages, the operation situation of water improvement projects and the fluoride content in drinking water were detected, and the dental fluorosis of children aged 8 to 12 was diagnosed. Results From 2010 to 2014, the normal operation rate of water improvement projects was 75.61% - 100.00%, the average of water fluorine content did not change, the differences were not statistically significant (F = 2.00, P > 0.05). The numbers of water improvement projects with water fluorine content in excessive amount was increased in the past five years which was only one project in 2010 - 2012 and was increased to two projects in 2013 and 2014. In 2010 -2014, the dental fluorosis prevalence rate of whole children was 9.45% (525/5 557), the dental fluorosis prevalence rate of exceeding-standard villages of water fluoride content was 42.40% (92/217), the dental fluorosis prevalence rate of qualified villages was 8.11% (433/5 340). The children's dental fluorosis prevalence rate of exceeding-standard villages of water fluoride content was higher than that in qualified villages; the differences were statistically significant (chi2 = 282.60, P < 0.05). Conclusions The operation rate of water-improving projects is mostly higher than 90%, and so is the qualification rate of fluoride content in drinking water. The operation condition and water quality of the water-improving projects in Hubei need to be improved. The prevalence of children dental fluorosis of affected villages has dropped significantly after low fluoride water is provided continuously120821: field[22]: In Chinese with English abstract RefMgr field[33]: Not in File?)Zhang, T. He, W.H. Feng, L.L. Huang, H.G.2017OEffect of doxorubicin-induced ovarian toxicity on mouse ovarian granulosa cells1-10&Regulatory Toxicology and Pharmacology86apoptosis Bax CELL CONCENTRATIONS DOXORUBICIN HORMONE LEVELS MEMBRANE Mitochondrial membrane potential mouse mRNA expression P ROS STUDY Toxicities TOXICITY 2/17/2017The objective of this study was to identify the effect of doxorubicin-induced ovarian toxicity on mouse ovarian granulosa cells. After granulosa cells were treated with doxorubicin at the final concentrations of 0, 0.4, 0.8, and 1.6 mug/ml for 24 h, cell apoptosis was detected by DAPI staining or caspase-3/7 fluorescence probe; ROS was determined by 2', 7'-dichlorodihydrofluorescin diacetate fluorescence probe; mitochondrial membrane potential was detected by rhodamine-123 fluorescence probe; and mRNA expression levels of Bax, Bcl-2, p53, FSHR, StAR, P450scc and P450arom were analyzed by RT-PCR. Results indicated that doxorubicin could induce apoptosis of granulosa cells (p < 0.01); increase ROS generation (p < 0.05 or p < 0.01); decrease mitochondrial membrane potential (p < 0.05); increase mRNA expression levels of Bax, Bcl-2, and p53 (p < 0.001); enhance mRNA expression level of StAR (p < 0.01 or p < 0.001); and inhibit mRNA expression level of P450scc in granulosa cells (p < 0.05 or p < 0.001). The mRNA expression levels of FSHR and P450arom were not influenced by doxorubicin. We suggest that the ovarian toxicity of doxorubicin was associated with apoptosis of granulosa cells, ROS accumulation, and decline of mitochondrial membrane potential in granulosa cells. In addition, cell apoptosis was regulated by Bax, Bcl-2, and p53, and hormone generation could be influenced by StAR and P450scc121105- field[33]: Not in FileB?PZheng, J. Zhao, W. Xu, K. Chen, Q. Chen, Y. Shen, Y. Xiao, L. Jiang, L. Chen, Y.2017^Interaction among hERG channel blockers is a potential mechanism of death in caffeine overdose European Journal of Pharmacology/online early: doi: 10.1016/j.ejphar.2017.02.018not published, 01 Mar 17ARREST CAFFEINE CARDIAC CARDIAC ARREST Consumption DATA DEATH DOE HEART IN VIVO INTERACTION IS MECHANISM Mechanisms NO OVERDOSE QT QT-interval QTc RABBIT REACH STUDY 2/16/2017wCaffeine overdose death is due to cardiac arrest, but its mechanism has not been explored in detail. In this study, our data showed that caffeine significantly prolonged the heart rate-corrected QT interval (QTc) of rabbits in vivo (P<0.05; n=7). Caffeine was also found to be a hERG channel blocker with an IC50 of 5.04mM (n=5). Although these two findings likely link caffeine overdose death with hERG channel blockade, the amount of caffeine consumption needed to reach the IC50 is very high. Further study demonstrated that addition another hERG blocker could lower the consumption of caffeine significantly, no matter whether two hERG blockers share the same binding sites. Our data does not rule out other possibility, however, it suggests that there is a potential causal relationship between caffeine overdose death with hERG channel and the interaction among these hERG blockers121003. field[33]: Not in FileB?SZidkova, M. Hlozek, T. Balik, M. Kopecky, O. Tesinsky, P. Svanda, J. Balikova, M.A.2017]Two cases of non-fatal intoxication with a novel street hallucinogen: 3-methoxy-phencyclidine Journal of Analytical Toxicology%online early: doi: 10.1093/jat/bkx009not published, 20 Feb 17'3-MeO-PCP 3-Methoxy-Phencyclidine ASSESSMENT case CASE REPORT Case-report CHROMATOGRAPHY CLINICAL DATA Europe HALLUCINOGEN Hallucinogens INTOXICATION IS Laboratories LABORATORY Liquid chromatography METABOLITE Metabolites method new psychoactive substance PHENCYCLIDINE Toxicities TOXICITY URINE2/2/2017S3-Methoxy-phencyclidine (3-MeO-PCP) is a structural derivative of the dissociative hallucinogen phencyclidine (PCP). Although PCP toxicity is well documented, little is known about this new psychoactive substance despite being available on the black market even in central Europe. The objective of this case report is to present clinical and laboratory data of analytically confirmed non-fatal intoxication of two subjects with 3-MeO-PCP. A preliminary assessment of potential metabolites excreted into urine was enabled using the liquid chromatography high resolution mass spectrometric method.120774$ field[33]: Not in FileB?Zipursky, J. Juurlink, D.N.2017WComment on Shively et al. "Acute salicylate poisoning: risk factors for severe outcome"Clinical Toxicology0online early: doi: 10.1080/15563650.2017.1290254not published, 03 Mar 17ACUTE Age analysis As author COMA DOE IS LACTATE LETTER MET MODEL Odds Ratio outcome POISONING RESPIRATORY RISK Risk factor RISK FACTORS SALICYLATE Sex STATISTICS Toxicities TOXICITY 2/17/2017121153/ field[33]: Not in File ?Zoorob, M.J. Salemi, J.L.2017wBowling alone, dying together: the role of social capital in mitigating the drug overdose epidemic in the United States1-9Drug and Alcohol Dependence173Association DATA DEATH Deaths DRUG drug overdose ENVIRONMENTAL EPIDEMIC EPIDEMIOLOGY evidence method methods MORTALITY OPIOID OVERDOSE SOCIAL Source STUDY TEMPORAL trends UNITED STATES vulnerability 1/25/2017BACKGROUND: Drug overdose deaths have risen precipitously over the last fifteen years. Substantial geographic variation, beyond a simple rural-urban dichotomy, exists in the concentration of overdose deaths, suggesting the existence of as-yet unidentified environmental variables that predict resilience (or vulnerability) to drug overdoses. Motivated by reports highlighting the role of community fragility in the opioid epidemic, we explore whether social capital attenuates overdose death rates. METHODS: We conducted an ecologic temporal trends study from 1999 to 2014 to investigate the association between mortality due to drug overdose and social capital. Data from multiple sources were compiled at the county-level to produce an analytic dataset comprising overdose mortality, social capital, and a host of potentially confounding variables indicated by the literature (N=49,664 county-years). Multinomial logistic regression was used to estimate the likelihood that a county falls in low (<4 deaths per 100,000), moderate, or high (>16 deaths per 100,000) categories of annual overdose morality. RESULTS: We observed a strong and statistically significant inverse association between county-level social capital and age-adjusted mortality due to drug overdose (p<0.01). Compared to the lowest quintile of social capital, counties at the highest quintile were 83% less likely to fall in the "high-overdose" category and 75% less likely to fall in the "moderate-overdose" category. CONCLUSION: This study finds large-sample evidence that social capital protects communities against drug overdose. This finding could help guide policymakers in identifying where overdose epidemics are likely to occur and how to ameliorate them1208702 field[33]: Not in File K?4Zyoud, S.H. Waring, W.S. Al-Jabi, S.W. Sweileh, W.M.2017tGlobal cocaine intoxication research trends during 1975-2015: a bibliometric analysis of Web of Science publications6/Substance Abuse Treatment, Prevention, & Policy121BABUSE ACUTE agent analysis ANIMAL Animals As bibliometric Canada CLINICAL COCAINE cocaine toxicity DATABASE DETECTION EPIDEMIOLOGY EXPOSURE HEALTH impact INTOXICATION IS Laboratories LABORATORY MANAGEMENT METABOLISM method methods PUBLICATION reproductive toxicity RESEARCH Spain stimulant STUDY Toxicities TOXICITY trends2/2/2017BACKGROUND: Cocaine is subject to recreational abuse as a stimulant and psychoactive agent, which poses a major worldwide health problem. The aim of the present study was to perform a bibliometric analysis of publication related to cocaine intoxication an insight of the research trends at a global level to enable recommendations for future research strategies in this field. METHODS: Publications about cocaine intoxication were retrieved from the Web of Science (WoS) Core Collection database on December 28, 2016, and analysed regarding the following bibliometric indicators: research trends, document types, languages, countries/territories with their h-index, collaboration patterns, journals with their impact factors (IF), and institutions. RESULTS: In total, 2,902 scientific publications from 1975 to 2015 were retrieved from the WoS database. The annual number of publications related to cocaine toxicity increased slightly after 1990 and reached a peak of 148 in 1992, with an average of 103 publications per year. The USA outranked other countries/territories with 2,089 publications, of which 1,927 arose exclusively from the USA and 162 involved international collaborations. The h-index for all publications related to cocaine was 212, and the h-index for all publications related to cocaine intoxication was 99. Moreover, the USA had the highest h-index of 95, followed by Spain with h-index of 24, and Canada with h-index of 24. The main research topics were consistently reproductive toxicity, clinical management of acute cocaine exposure, laboratory methods for detection of exposure to cocaine, cocaine metabolism, and cocaine toxicity in animals. CONCLUSIONS: This is the first bibliometric approach to examining research related to cocaine toxicity and shows that research activity has become more global and extensive since 1990. The USA remains the leading country regarding published literature, the highest h-index, and greatest role in international collaborations120812+ field[33]: Not in FilePKOJI/**refs.frm 0B< !// !HPRIMARYyearIndex 6ByP/) idreference_type text_stylesauthoryear title pages secondary_title volume numbernumber_of_volumessecondary_authorplace_published publishersubsidiary_authoredition keywords type_of_workdate2)  abstractlabelurltertiary_titletertiary_author notes isbn custom_1 custom_2 custom_3 custom_4alternate_titleaccession_number call_number short_title custom_5 custom_6sectionoriginal_publicationH) reprint_editionreviewed_itemauthor_addressimagecaption custom_7 electronic_resource_number link_to_pdf translated_author translated_titlename_of_databasedatabase_providerresearch_notes language access_datelast_modified_date !! H!H!H! (H! 3H! >H! IH! TH!_H!jH!uH! H!H!H! H! H!H! H!H!H!H!H! H! H! H! H! %H! 0H!;H!FH! QH! \H! gH! rH!}H!H!H!H!H!H!H! H! H! H! H! H!H! H!H! 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