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J Soler, P Ferentinos, C Prats, S Miret, M Giralt, V Peralta, L Fañanás, M Fatjó-Vilas
INTRODUCTION: This study explored schizotypy as a familial liability marker for schizophrenia-spectrum disorders (SSD) by examining: 1) the aggregation of schizotypy in families with a SSD patient, 2) whether familial resemblance of schizotypy is associated with ridge dissociations (RD), another SSD liability marker, 3) whether schizotypy aggregation patterns influence patients' psychopathology. METHODS: The sample comprised 30 SSD patients and 82 healthy first-degree relatives...
September 29, 2016: Journal of Psychiatric Research
T M M Joergensen, K Christensen, J S Lindholt, L A Larsen, A Green, K Houlind
No abstract text is available yet for this article.
August 2016: Journal of Vascular Surgery
Brian H Bornstein, Jonathan M Golding, Jeffrey Neuschatz, Christopher Kimbrough, Krystia Reed, Casey Magyarics, Katherine Luecht
The advantages and disadvantages of jury simulation research have often been debated in the literature. Critics chiefly argue that jury simulations lack verisimilitude, particularly through their use of student mock jurors, and that this limits the generalizabilty of the findings. In the present article, the question of sample differences (student v. nonstudent) in jury research was meta-analyzed for 6 dependent variables: 3 criminal (guilty verdicts, culpability, and sentencing) and 3 civil (liability verdicts, continuous liability, and damages)...
October 20, 2016: Law and Human Behavior
Paulo José Lorenzoni, Cláudia Suemi Kamoi Kay, Cristiane Cavalet, Raquel C Arndt, Lineu Cesar Werneck, Rosana Herminia Scola
The spectrum of clinical and electrophysiological features in hereditary neuropathy with liability to pressure palsies (HNPP) is broad. We analyze a series of Brazilian patients with HNPP. Correlations between clinical manifestations, laboratory features, electrophysiological analyze, histological and molecular findings were done. In five cases, more than one episode occurred before diagnosis. Median nerve in the carpal tunnel at the wrist, ulnar nerve in its groove at the elbow, fibular nerve in the head of the fibula at the knee, radial nerve in its groove of the humerus and suprascapular nerve in its notch at the supraspinous fossa were found as focal neuropathies...
September 30, 2016: Neurology International
Delilah F G Hendriks, Lisa Fredriksson Puigvert, Simon Messner, Wolfgang Mortiz, Magnus Ingelman-Sundberg
Drug-induced cholestasis (DIC) is poorly understood and its preclinical prediction is mainly limited to assessing the compound's potential to inhibit the bile salt export pump (BSEP). Here, we evaluated two 3D spheroid models, one from primary human hepatocytes (PHH) and one from HepaRG cells, for the detection of compounds with cholestatic liability. By repeatedly co-exposing both models to a set of compounds with different mechanisms of hepatotoxicity and a non-toxic concentrated bile acid (BA) mixture for 8 days we observed a selective synergistic toxicity of compounds known to cause cholestatic or mixed cholestatic/hepatocellular toxicity and the BA mixture compared to exposure to the compounds alone, a phenomenon that was more pronounced after extending the exposure time to 14 days...
October 19, 2016: Scientific Reports
Volker M Lauschke, Magnus Ingelman-Sundberg
Responses to drugs and pharmacological treatments differ considerably between individuals. Importantly, only 50%-75% of patients have been shown to react adequately to pharmacological interventions, whereas the others experience either a lack of efficacy or suffer from adverse events. The liver is of central importance in the metabolism of most drugs. Because of this exposed status, hepatotoxicity is amongst the most common adverse drug reactions and hepatic liabilities are the most prevalent reason for the termination of development programs of novel drug candidates...
October 12, 2016: International Journal of Molecular Sciences
Torbjörn U C Järbe, Jimit Girish Raghav
The phenomenon of consuming synthetic cannabinoids ("Spice") for recreational purposes is a fairly recent trend. However, consumption of cannabis dates back millennia, with numerous accounts written on the experience of its consumption, and thousands of scientific reports published on the effects of its constituents in laboratory animals and humans. Here, we focus on consolidating the scientific literature on the effects of "Spice" compounds in various behavioral assays, including assessing abuse liability, tolerance, dependence, withdrawal, and potential toxicity...
October 18, 2016: Current Topics in Behavioral Neurosciences
Tristram A Lett, Henrik Walter, Eva J Brandl
Genetic variation underlies both the response to antidepressant treatment and the occurrence of side effects. Over the past two decades, a number of pharmacogenetic variants, among these the SCL6A4, BDNF, FKBP5, GNB3, GRIK4, and ABCB1 genes, have come to the forefront in this regard. However, small effects sizes, mixed results in independent samples, and conflicting meta-analyses results led to inherent difficulties in the field of pharmacogenetics translating these findings into clinical practice. Nearly all antidepressant pharmacogenetic variants have potentially pleiotropic effects in which they are associated with major depressive disorder, intermediate phenotypes involved in emotional processes, and brain areas affected by antidepressant treatment...
October 17, 2016: CNS Drugs
Alexander U Brandt, Elena Meinert-Bohn, Jan Leo Rinnenthal, Hanna Zimmermann, Janine Mikolajczak, Timm Oberwahrenbrock, Sebastian Papazoglou, Caspar F Pfüller, Johann Schinzel, Björn Tackenberg, Friedemann Paul, Katrin Hahn, Judith Bellmann-Strobl
BACKGROUND: The PMP22 gene encodes a protein integral to peripheral myelin. Its deletion leads to hereditary neuropathy with liability to pressure palsies (HNPP). PMP22 is not expressed in the adult central nervous system, but previous studies suggest a role in CNS myelin development. The objective of this study was to identify potential structural and functional alterations in the afferent visual system in HNPP patients. METHODS: Twenty HNPP patients and 18 matched healthy controls (HC) were recruited in a cross-sectional study...
2016: PloS One
Sarah A Altınoğlu, Ming Wang, Kathleen Q Li, Yuyang Li, Qiaobing Xu
The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor, mutated or inactive in a large percentage of human cancers. Restoring PTEN activity in cancer cells through gene therapy has shown to inhibit cell growth and induce apoptosis, particularly in cells with a PTEN deficiency. Gene therapy, however, comes with some inherent risks such as triggering an immune response and permanent off target effects. Nanoparticle assisted protein delivery could mitigate these liabilities while maintaining therapeutic integrity...
October 17, 2016: Biomaterials Science
Felix Klickermann
Attempts through the US courts to hold the corporations responsible for the production of dioxin-contaminated herbicides used by the US military in the 1960s and early 1970s liable for their ongoing health consequences have failed. This article scrutinizes the most recent judgement - that of the United States District Court for the Eastern District of New York handed down in 2005 following a lawsuit brought by the Vietnam Association of Victims of Agent Orange/dioxin (VAVA). It is argued that despite this judgement there is the potential to bring a further legal case, with some prospect of success, on the basis of: (i) debatable legal judgements in the 2005 decision; (ii) new scientific evidence on the health effects of exposure to Agent Orange; and (iii) cases brought in other jurisdictions...
October 16, 2016: Medicine, Conflict, and Survival
Harriet Gaskell, Parveen Sharma, Helen E Colley, Craig Murdoch, Dominic P Williams, Steven D Webb
More predictive in vitro liver models are a critical requirement for preclinical screening of compounds demonstrating hepatotoxic liability. 3D liver spheroids have been shown to have an enhanced functional lifespan compared to 2D monocultures; however a detailed characterisation of spatiotemporal function and structure of spheroids still needs further attention before widespread use in industry. We have developed and characterized the structure and function of a 3D liver spheroid model formed from C3A hepatoma cells...
June 1, 2016: Toxicology Research
Tyler A Johnson, Laura Milan-Lobo, Tao Che, Madeline Ferwerda, Eptisam Lambo, Nicole L McIntosh, Fei Li, Li He, Nicholas Lorig-Roach, Phillip Crews, Jennifer Lynne Whistler
Opioid therapeutics are excellent analgesics, whose utility is compromised by dependence. Morphine (1) and its clinically relevant derivatives such as OxyContin® (4), Vicodin® (5) and Dilaudid® (6) are "biased" agonists at the µ opioid receptor (OR), wherein they engage G-protein signaling but poorly engage β-arrestin and the endocytic machinery. In contrast, the endorphins, met-enkephalin (14) and β-endorphin (15), endogenous peptide agonists for ORs, are more potent analgesics then 1, show reduced liability for tolerance and dependence, and engage both G-protein and β-arrestin pathways as "balanced" agonists...
October 17, 2016: ACS Chemical Neuroscience
Valerie Michaelson, William Pickett, Eleanor Vandemeer, Brian Taylor, Colleen Davison
Health perceptions adopted during childhood lay foundations for adult health trajectories and experiences. This study used a sequential mixed methods design to generate new evidence about child perceptions of health in two samples of Canadian children. A core qualitative study was followed by a complementary quantitative analysis to aid interpretation. Generational theory was used as a lens through which to interpret all data. Findings suggested that good health is perceived as customized and subjective. The strengths and liabilities of these perceptions are discussed, as well as implications for health promotion and prevention strategies...
2016: International Journal of Qualitative Studies on Health and Well-being
Lori A Stolz, Uwe Stolz, J Matthew Fields, Turandot Saul, Michael Secko, Matthew J Flannigan, Johnathan M Sheele, Robert P Rifenburg, Anthony J Weekes, Elaine B Josephson, John Bedolla, Dana M Resop, Jonathan Dela Cruz, Megan Boysen-Osborn, Terrell Caffery, Charlotte Derr, Rimon Bengiamin, Gerardo Chiricolo, Brandon Backlund, Jagdipak Heer, Robert J Hyde, Srikar Adhikari
OBJECTIVES: Emergency ultrasound (EUS) has been recognized as integral to the training and practice of emergency medicine (EM). The Council of Emergency Medicine Residency-Academy of Emergency Ultrasound (CORD-AEUS) consensus document provides guidelines for resident assessment and progression. The Accredited Council for Graduate Medical Education (ACGME) has adopted the EM Milestones for assessment of residents' progress during their residency training which includes demonstration of procedural competency in bedside ultrasound...
October 14, 2016: Academic Emergency Medicine: Official Journal of the Society for Academic Emergency Medicine
Jeffrey J Coleman, Tomomi Komura, Julia Munro, Michael P Wu, Rakhee R Busanelli, Angela N Koehler, Méryl Thomas, Florence F Wagner, Edward B Holson, Eleftherios Mylonakis
AIM: Caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester (CAPE), the major constituent of propolis, is able to increase the survival of the nematode Caenorhabditis elegans after infection with the fungal pathogen Candida albicans. RESULTS: CAPE increases the expression of several antimicrobial proteins involved in the immune response to C. albicans. Structural derivatives of CAPE were synthesized to identify structure-activity relationships and decrease metabolic liability, ultimately leading to a compound that has similar efficacy, but increased in vivo stability...
October 14, 2016: Future Medicinal Chemistry
Emel Oğuz-Akarsu, Zeynep Aydin-Özemir, Nerses Bebek, Candan Gürses, Ayşen Gökyiğit, Betül Baykan
Status epilepticus (SE) is rarely described in patients with juvenile myoclonic epilepsy (JME), and little is known about its frequency, subtypes, and predictors and the prognosis of these patients. In this retrospective study, we aimed to analyze the incidence of SE in patients with JME and emphasize the risk factors and long-term outcome of SE in an epilepsy outpatient-based cohort. We included patients with JME with a history of predominant myoclonic seizures and at least one diagnostic EEG with normal background activity and bursts of typical ≥3-Hz generalized spike-polyspike and waves...
October 10, 2016: Epilepsy & Behavior: E&B
Vidhi V Shah, Marshall B Kapp, Stephen E Wolverton
Malpractice risk is a common source of concern for the practicing physician. Dermatologists experience fewer lawsuits than most other specialists in medicine, but the risk is not negligible. All physicians should familiarize themselves with areas of potential risk and avoid medico-legal pitfalls. We present Part I of a two-part series addressing medico-legal questions common to most practitioners that cause a great deal of anxiety. Part I will focus upon risk management and prevention of future malpractice lawsuits, and Part II deals with suggestions and guidance once a lawsuit occurs...
October 12, 2016: American Journal of Clinical Dermatology
Agnieszka Butwicka, Niklas Långström, Henrik Larsson, Sebastian Lundström, Eva Serlachius, Catarina Almqvist, Louise Frisén, Paul Lichtenstein
Despite limited and ambiguous empirical data, substance use-related problems have been assumed to be rare among patients with autism spectrum disorders (ASD). Using Swedish population-based registers we identified 26,986 individuals diagnosed with ASD during 1973-2009, and their 96,557 non-ASD relatives. ASD, without diagnosed comorbidity of attention deficit hyperactivity disorder (ADHD) or intellectual disability, was related to a doubled risk of substance use-related problems. The risk of substance use-related problems was the highest among individuals with ASD and ADHD...
October 12, 2016: Journal of Autism and Developmental Disorders
Michael Ermisch, Anna Bucsics, Patricia Vella Bonanno, Francis Arickx, Alexander Bybau, Tomasz Bochenek, Marc van de Casteele, Eduardo Diogene, Jurij Fürst, Kristina Garuolienė, Martin van der Graaff, Jolanta Gulbinovič, Alan Haycox, Jan Jones, Roberta Joppi, Ott Laius, Irene Langner, Antony P Martin, Vanda Markovic-Pekovic, Laura McCullagh, Einar Magnusson, Ellen Nilsen, Gisbert Selke, Catherine Sermet, Steven Simoens, Robert Sauermann, Ad Schuurman, Ricardo Ramos, Vera Vlahovic-Palcevski, Corinne Zara, Brian Godman
Payers are a major stakeholder in any considerations and initiatives concerning adaptive licensing of new medicinal products, also referred to as Medicines Adaptive Pathways to patients (MAPPs). Firstly, the scope and necessity of MAPPs need further scrutiny, especially with regard to the definition of unmet need. Conditional approval pathways already exist for new medicines for seriously debilitating or life-threatening diseases and only a limited number of new medicines are innovative. Secondly, MAPPs will result in new medicines on the market with limited evidence about their effectiveness and safety...
2016: Frontiers in Pharmacology
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