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Nicolas Hoertel, Hadi Faiz, Guillaume Airagnes, Carlos Blanco, Rachel Pascal De Raykeer, Silvia Franco, Géraldine Ducoutumany, Cédric Lemogne, Frédéric Limosin
BACKGROUND: Heavy drinkers are at high risk for suicide attempt and suicide. Multiple factors, when examined in isolation, have been implicated in the risk of suicide attempt in this population. In this report, we present a comprehensive model of the 3-year risk of suicide attempt in heavy drinkers using a longitudinal nationally representative study, the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; wave 1, 2001-2002; wave 2, 2004-2005). METHODS: We used structural equation modeling to simultaneously examine effects of four broad groups of clinical factors previously identified as potential predictors of attempted suicides: 1) alcohol use disorder severity, 2) severity of comorbidity, 3) sociodemographic characteristics and 4) help-seeking for alcohol problems...
March 7, 2018: Drug and Alcohol Dependence
Jean-Francois Fournier, Claire Bouix-Peter, Denis Duvert, Anne-Pascale Luzy, Gilles Ouvry
Phototoxicity occurs when UV irradiation causes otherwise benign compounds to become irritant, sensitizers or even genotoxic. This toxicity is particularly a concern after topical application and in dermatological programs where skin irritation can be incompatible with the desired therapeutic outcome. This brief article establishes that the intrinsic Property Forecast Index (iPFI) can be used to evaluate the probability of a compound being phototoxic and gives medicinal chemists a practical tool to handle this liability...
March 16, 2018: Journal of Medicinal Chemistry
Zoë W Hawks, Natasha Marrus, Anne L Glowinski, John N Constantino
Previous research has suggested that behavioral comorbidity is the rule rather than the exception in autism. The present study aimed to trace the respective origins of autistic and general psychopathologic traits-and their association-to infancy. Measurements of autistic traits and early liability for general psychopathology were assessed in 314 twins at 18 months, ascertained from the general population using birth records. 222 twins were re-evaluated at 36 months. Standardized ratings of variation in social communication at 18 months were highly heritable and strongly predicted autistic trait scores at 36 months...
March 16, 2018: Journal of Abnormal Child Psychology
Amr El Noury, Osama Azmy, Jehan Alsharnoubi, Sameh Salama, Ahmed Okasha, Weaam Gouda
OBJECTIVES: Pathophysiological similarity exists between gestational diabetes mellitus (GDM) and type 2 diabetes mellitus with common genetic origin. Genetic liability for GDM in our population is still not researched. The goal was to reveal the genotypic and allele frequency differences of 2 single nucleotide polymorphisms (SNPs) namely, CDKAL1 (rs7754840) and CDKN2A/2B (rs10811661) between GDM pregnancies and normal pregnancies. We assessed them by real time polymerase chain reaction using Taqman® allelic discrimination assays...
March 15, 2018: BMC Research Notes
Bishnu P Joshi, Joseph Hardie, Michelle E Farkas
The accumulation of therapeutic and imaging agents at sites of interest is critical to their efficacy. Similarly, off-target effects (especially toxicity) are a major liability for these agents. For this reason, the use of delivery vehicles to improve the distribution characteristics of bio-active agents has become ubiquitous in the field. However, the majority of traditionally employed, cargo-bearing entities rely on passive accumulation. Even in cases where 'targeting' functionalities are used, the agents must first reach the site in order for the ligand-receptor interaction to occur...
March 15, 2018: Chemistry: a European Journal
Andreas Kling, Katja Jantos, Helmut Mack, Wilfried Hornberger, Gisela Backfisch, Yanbin Lao, Marjoleen Nijsen, Beatrice Rendenbach-Mueller, Achim Moeller
Dysregulation of calpains 1 and 2 has been implicated in a variety of pathological disorders including ischemia/reperfusion injuries, kidney diseases, cataract formation, and neurodegenerative diseases such as Alzheimer's disease (AD). 2-(3-Phenyl-1 H )-pyrazol-1-yl)nicotinamides represent a series of novel and potent calpain inhibitors with high selectivity and in vivo efficacy. However, carbonyl reduction leading to the formation of the inactive hydroxyamide was identified as major metabolic liability in monkey and human, a pathway not reflected by routine absorption, distribution, metabolism, and excretion (ADME) assays...
March 8, 2018: ACS Medicinal Chemistry Letters
Leandro Nóbrega, Ricardo Jorge Dinis-Oliveira
New psychoactive substances (NPS), often referred as 'legal highs' or 'designer drugs', are derivatives and analogs of existing psychoactive drugs that are introduced in the recreational market to circumvent existing legislation on drugs of abuse. This work aims to review the state-of-the-art regarding chemical, molecular pharmacology, and in vitro and in vivo data on toxicokinetics of the potent synthetic cathinone α-pyrrolidinovalerophenone (α-PVP or flakka or zombie drug). Chemical, pharmacological, toxicological, and clinical effects of α-PVP were searched in PubMed (U...
March 14, 2018: Drug Metabolism Reviews
Ahilan Sivaganesan, Brandon Hirsch, Frank M Phillips, Matthew J McGirt
Here, we systematically review clinical studies that report morbidity and outcomes data for cervical and lumbar surgeries performed in ambulatory surgery centers (ASCs). We focus on anterior cervical discectomy and fusion (ACDF), posterior cervical foraminotomy, cervical arthroplasty, lumbar microdiscectomy, lumbar laminectomy, and minimally invasive transforaminal interbody fusion (TLIF) and lateral lumbar interbody fusion, as these are prevalent and surgical spine procedures that are becoming more commonly performed in ASC settings...
March 12, 2018: Neurosurgery
Juan Andrés Abin-Carriquiry, Marcela Martínez-Busi, Martín Galvalisi, Manuel Minteguiaga, José Pedro Prieto, María Cecilia Scorza
Adulteration is a common practice in the illicit drugs market, but the psychoactive and toxic effects provided by adulterants are clinically underestimated. Coca-paste (CP) is a smokable form of cocaine which has an extremely high abuse liability. CP seized samples are sold adulterated; however, qualitative and quantitative data of CP adulteration in forensic literature is still scarce. Besides, it is unknown if adulterants remain stable when CP is heated. This study was designed to report the chemical content of an extensive series of CP seized samples and to demonstrate the stability (i...
March 13, 2018: Neurotoxicity Research
Su-Hee Cho, Ji-Ye Lee, Kyeong-Hwa Ryu, Dae Chul Suh
Purpose: False positive diagnoses of cerebral aneurysm via magnetic resonance angiography (MRA) screening may increase unnecessary cerebral catheter angiography. The purpose of this study was to investigate the effects of medical liability on medical decision-making during radiologic interpretation. Materials and Methods: We included 56 consecutive patients who were referred with suspected aneurysm based on MRA or computed tomography angiography (CTA) and showed no aneurysm on subsequent digital subtraction angiography (DSA)...
March 2018: Neurointervention
Joy Y Feng
Nucleoside and nucleotide analogs have played significant roles in antiviral therapies and are valued for their impressive potency and high barrier to resistance. They have been approved for treatment of herpes simplex virus-1, HIV, HBV, HCV, and influenza, and new drugs are being developed for the treatment of RSV, Ebola, coronavirus MERS, and other emerging viruses. However, this class of compounds has also experienced a high attrition rate in clinical trials due to toxicity. In this review, we discuss the utility of different biochemical and cell-based assays and provide recommendations for assessing toxicity liability before entering animal toxicity studies...
January 2018: Antiviral Chemistry & Chemotherapy
Ellen S Deutsch
Physician psychological wellness is an emergent outcome resulting from dynamic interactions among complex conditions. We may enhance opportunities for physician wellness by applying principles developed to improve another emergent outcome: patient safety. The Safety I approach to patient safety focuses on "what went wrong" and considers humans a liability. Safety II is a powerful complementary approach that focuses on "what went right" and values human creativity. These contrasting perspectives are described in the context of patient safety, but the underlying principles have relevance for physician psychological wellness...
March 1, 2018: Otolaryngology—Head and Neck Surgery
Jacqueline Ho, Jhih-Shyang Shih, Lucija Muehlenbachs, Clayton Munnings, Alan Krupnick
Inactive oil and gas wells present an environmental hazard if not properly plugged. Upon drilling a well, operators are required to post a bond, which ensures both that the operator has an incentive to plug and abandon (P&A) at the end of the well's life, and that, if the state is left with the liability of managing "orphaned" wells, it can cover the cost of P&A. Using data from 13 state agencies on their expenditures to plug orphan wells, we provide new estimates of P&A costs in the United States and compare P&A costs to bonds...
March 13, 2018: Environmental Science & Technology
Emily Baker, Karl Michael Schmidt, Rebecca Sims, Michael C O'Donovan, Julie Williams, Peter Holmans, Valentina Escott-Price, With The Gerad Consortium
Polygenic risk scores (PRSs) are a method to summarize the additive trait variance captured by a set of SNPs, and can increase the power of set-based analyses by leveraging public genome-wide association study (GWAS) datasets. PRS aims to assess the genetic liability to some phenotype on the basis of polygenic risk for the same or different phenotype estimated from independent data. We propose the application of PRSs as a set-based method with an additional component of adjustment for linkage disequilibrium (LD), with potential extension of the PRS approach to analyze biologically meaningful SNP sets...
March 12, 2018: Genetic Epidemiology
Jian Payandeh, David H Hackos
The voltage-gated sodium (Nav) channel Nav1.7 has been the focus of intense investigation in recent years. Human genetics studies of individuals with gain-of-function and loss-of-function mutations in the Nav1.7 channel have implicated Nav1.7 as playing a critical role in pain. Therefore, selective inhibition of Nav1.7 represents a potentially new analgesic strategy that is expected to be devoid of the significant liabilities associated with available treatment options. Although the identification and development of selective Nav channel modulators have historically been challenging, a number of recent publications has demonstrated progression of increasingly subtype-selective small molecules and peptides toward potential use in preclinical or clinical studies...
March 13, 2018: Handbook of Experimental Pharmacology
Nishant Ganesh Kumar, Nicholas Hricz, Brian C Drolet
BACKGROUND: Carpal tunnel release (CTR) is the most common hand surgery operation performed in the United States. While serious complications are rare, they can be life-altering to patients. In some cases, patients will pursue malpractice claims against the surgeon. This study aimed to understand the patient, procedure, and surgeon factors involved in CTR malpractice litigation. METHODS: The Westlaw legal database was queried for all recorded CTR malpractice cases resulting in jury verdicts and settlements...
March 1, 2018: Hand: Official Journal of the American Association for Hand Surgery
Sumit Mistry, Judith R Harrison, Daniel J Smith, Valentina Escott-Price, Stanley Zammit
BACKGROUND: Identifying the phenotypic manifestations of increased genetic liability for depression (MDD) and bipolar disorder (BD) can enhance understanding of their aetiology. The polygenic risk score (PRS) derived using data from genome-wide-association-studies can be used to explore how genetic risk is manifest in different samples. AIMS: In this systematic review, we review studies that examine associations between the MDD and BD polygenic risk scores and phenotypic outcomes...
February 15, 2018: Journal of Affective Disorders
Catherine R Alexander, Fiona Bogossian
BACKGROUND: An allegation of negligence or an adverse outcome during childbirth can lead to clinical investigation of a midwife's practice. Anecdotal evidence suggests midwives find this stressful and disturbing. AIM: Synthesise the evidence relating to midwives' experiences of investigation and the effects on clinical practice and personal wellbeing. METHODS: Two database searches were conducted between 2015 and 2016 to identify primary research published between 1990 and 2016...
March 7, 2018: Women and Birth: Journal of the Australian College of Midwives
N Dietis, H Niwa, R Tose, J McDonald, V Ruggieri, M Filaferro, G Vitale, L Micheli, C Ghelardini, S Salvadori, G Calo, R Guerrini, D J Rowbotham, D G Lambert
BACKGROUND AND PURPOSE: Targeting more than one opioid receptor type simultaneously may have analgesic advantages in reduced side effect profile. We have evaluated the mixed MOP (μ, mu) agonist/DOP (δ, delta) antagonist UFP-505 in vitro and in vivo. EXPERIMENTAL APPROACH: We measured receptor density and function in single MOP, DOP and MOP/DOP double expression systems. GTPγ35 S binding, cAMP formation and arrestin recruitment were measured. Antinociceptive activity was measured in vivo using tail withdrawal and paw pressure tests following acute and chronic treatment...
March 10, 2018: British Journal of Pharmacology
Rao Mukkavilli, Gajanan Jadhav, Subrahmanyam Vangala
BACKGROUND: Drug transporters function as gatekeepers and modulate drug access into the body and various tissues. Thus a thorough and precise understanding of transporter liability for compound uptake and efflux is critical during drug development. METHODS: In the present study, we assessed the apparent permeability (Papp) and compared the efflux ratio of various compounds in stably transfected Madin-Darby Canine Kidney (MDCKII) cells overexpressing human P-gp (MDCKII-P-gp), human BCRP (MDCKII-BCRP), wild type (MDCKII-WT), and Caco-2 cell monolayers...
March 7, 2018: Current Pharmaceutical Biotechnology
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