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https://www.readbyqxmd.com/read/28926002/polygenic-loading-for-major-depression-is-associated-with-specific-medical-comorbidity
#1
T H McCoy, V M Castro, L Snapper, K Hart, J L Januzzi, J C Huffman, R H Perlis
Major depressive disorder frequently co-occurs with medical disorders, raising the possibility of shared genetic liability. Recent identification of 15 novel genetic loci associated with depression allows direct investigation of this question. In cohorts of individuals participating in biobanks at two academic medical centers, we calculated polygenic loading for risk loci reported to be associated with depression. We then examined the association between such loading and 50 groups of clinical diagnoses, or topics, drawn from these patients' electronic health records, determined using a novel application of latent Dirichilet allocation...
September 19, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28925238/the-art-of-the-deposition-teaching-residents-about-medical-liability
#2
Ross F Goldberg, Kenneth D Goldberg, Daniel Caruso
No abstract text is available yet for this article.
February 2017: Bulletin of the American College of Surgeons
https://www.readbyqxmd.com/read/28922023/fatty-acid-synthase-fasn-as-a-therapeutic-target-in-breast-cancer
#3
Javier A Menendez, Ruth Lupu
Ten years ago, we put forward the metabolo-oncogenic nature of fatty acid synthase (FASN) in breast cancer. Since the conception of this hypothesis, which provided a model to explain how FASN is intertwined with various signaling networks to cell-autonomously regulate breast cancer initiation and progression, FASN has received considerable attention as a therapeutic target. However, despite the ever-growing evidence demonstrating the involvement of FASN as part of the cancer-associated metabolic reprogramming, translation of the basic science-discovery aspects of FASN blockade to the clinical arena remains a challenge...
September 18, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28921646/how-often-are-drugs-made-available-under-the-food-and-drug-administration-s-expanded-access-process-approved
#4
Amy E McKee, André O Markon, Kirk M Chan-Tack, Peter Lurie
In this review of individual patient expanded-access requests to the Center for Drug Evaluation and Research for the period Fiscal Year 2010 to Fiscal Year 2014, we evaluated the number of applications received and the number allowed to proceed. We also evaluated whether drugs and certain biologics obtained under expanded access went on to be approved by the Food and Drug Administration. Finally, we considered concerns that adverse events occurring during expanded access might place sponsors at risk for legal liability...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28921525/comorbid-symptoms-of-inattention-autism-and-executive-cognition-in-youth-with-putative-genetic-risk
#5
Anne B Arnett, Brianna E Cairney, Arianne S Wallace, Jennifer Gerdts, Tychele N Turner, Evan E Eichler, Raphael A Bernier
BACKGROUND: Symptoms of autism spectrum disorder (ASD) and inattention (IA) are highly comorbid and associated with deficits in executive cognition. Cognitive deficits have been posited as candidate endophenotypes of psychiatric traits, but few studies have conceptualized cognitive deficits as psychiatric comorbidities. The latter model is consistent with a latent factor reflecting broader liability to neuropsychological dysfunction, and explains heterogeneity in the cognitive profile of individuals with ASD and IA...
September 18, 2017: Journal of Child Psychology and Psychiatry, and Allied Disciplines
https://www.readbyqxmd.com/read/28918038/strategies-for-in%C3%A2-vivo-screening-and-mitigation-of-hepatotoxicity-associated-with-antisense-drugs
#6
Piotr J Kamola, Klio Maratou, Paul A Wilson, Kay Rush, Tanya Mullaney, Tom McKevitt, Paula Evans, Jim Ridings, Probash Chowdhury, Aude Roulois, Ann Fairchild, Sean McCawley, Karen Cartwright, Nigel J Gooderham, Timothy W Gant, Kitty Moores, Stephen A Hughes, Mark R Edbrooke, Kenneth Clark, Joel D Parry
Antisense oligonucleotide (ASO) gapmers downregulate gene expression by inducing enzyme-dependent degradation of targeted RNA and represent a promising therapeutic platform for addressing previously undruggable genes. Unfortunately, their therapeutic application, particularly that of the more potent chemistries (e.g., locked-nucleic-acid-containing gapmers), has been hampered by their frequent hepatoxicity, which could be driven by hybridization-mediated interactions. An early de-risking of this liability is a crucial component of developing safe, ASO-based drugs...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28916453/making-the-legal-and-ethical-case-for-universal-screening-for-postpartum-mood-and-anxiety-disorders-in-pediatric-primary-care
#7
Amy Lewis Gilbert, Casey Balio, Nerissa S Bauer
Postpartum depression (PPD), part of a larger spectrum of perinatal mood and anxiety disorders, affects up to 15% of women following the birth of an infant. Fathers may also be affected. PPD not only affects caregivers, but also impacts infants through mechanisms such as inadequate caregiver-infant interactions and non-adherence to safety practices. The negative impact on infants may extend across the life course through adulthood. This article seeks to move the needle toward universal screening for PPD using validated tools in pediatric primary care settings for new caregivers by making the legal and ethical case for this course of action in a manner that is both compelling and accessible for clinicians...
September 12, 2017: Current Problems in Pediatric and Adolescent Health Care
https://www.readbyqxmd.com/read/28914863/-chronic-gastritis-instructions-for-use-of-medications
#8
V I Simanenkov, S S Vyalov
The paper highlights the features of drug use in the legal aspect. It analyzes instructions for medical use of proton pump inhibitors (PPIs) and gastric protective agents. Taking into account the characteristics of indications registered in the instruction, the authors discuss the possibility of using various PPIs. The instruction for medical application is an official document approved by the Ministry of Health, the basis of which is the data of trials carried out by a manufacturer, and it should be a key or fundamental source for a physician in choosing a medication...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28912683/nano-scale-biophysical-and-structural-investigations-on-intact-and-neuropathic-nerve-fibers-by-simultaneous-combination-of-atomic-force-and-confocal-microscopy
#9
Gonzalo Rosso, Ivan Liashkovich, Peter Young, Victor Shahin
The links between neuropathies of the peripheral nervous system (PNS), including Charcot-Marie-Tooth1A and hereditary neuropathy with liability to pressure palsies, and impaired biomechanical and structural integrity of PNS nerves remain poorly understood despite the medical urgency. Here, we present a protocol describing simultaneous structural and biomechanical integrity investigations on isolated nerve fibers, the building blocks of nerves. Nerve fibers are prepared from nerves harvested from wild-type and exemplary PNS neuropathy mouse models...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28911631/new-psychoactive-substances-of-natural-origin-a%C3%A2-brief-review
#10
REVIEW
Ling-Yi Feng, Altansuvd Battulga, Eunyoung Han, Heesun Chung, Jih-Heng Li
Plant-based drugs of abuse are as old as recorded human history. Although traditional addictive substances, such as opium, cannabis and coca, have been controlled by the United Nations anti-drug conventions, many, if not most, natural plants with addictive or abuse liability remain elusive. Therefore, the United Nations Office on Drugs and Crime (UNODC) has warned the emerging threat from new psychoactive substances (NPS), which are mostly derived or modified from the constituents of natural origin. For example, synthetic cannabinoids and synthetic cathinones are derived from the cannabis and khat plant, respectively...
July 2017: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28903679/distinctive-facial-cues-predict-leadership-rank-and-selection
#11
Daniel E Re, Nicholas Rule
Facial appearance correlates with leadership, both in terms of who is chosen (leader selection) and how they do (leader success). Leadership theories suggest that exceptional individuals acquire positions as leaders. Exceptional traits can differ between domains, however, and so the qualities valued in leaders in one occupation may not match those valued among leaders in another. To test this, we compared the relationship between facial appearance and leadership across two domains: law firms and mafia families...
September 2017: Personality & Social Psychology Bulletin
https://www.readbyqxmd.com/read/28902459/exome-sequences-of-multiplex-multigenerational-families-reveal-schizophrenia-risk-loci-with-potential-implications-for-neurocognitive-performance
#12
Mark Z Kos, Melanie A Carless, Juan Peralta, Joanne E Curran, Ellen E Quillen, Marcio Almeida, August Blackburn, Lucy Blondell, David R Roalf, Michael F Pogue-Geile, Ruben C Gur, Harald H H Göring, Vishwajit L Nimgaonkar, Raquel E Gur, Laura Almasy
Schizophrenia is a serious mental illness, involving disruptions in thought and behavior, with a worldwide prevalence of about one percent. Although highly heritable, much of the genetic liability of schizophrenia is yet to be explained. We searched for susceptibility loci in multiplex, multigenerational families affected by schizophrenia, targeting protein-altering variation with in silico predicted functional effects. Exome sequencing was performed on 136 samples from eight European-American families, including 23 individuals diagnosed with schizophrenia or schizoaffective disorder...
September 13, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28899997/improving-disease-prediction-by-incorporating-family-disease-history-in-risk-prediction-models-with-large-scale-genetic-data
#13
Jungsoo Gim, Wonji Kim, Soo Heon Kwak, Hosik Choi, Changyi Park, Kyong Soo Park, Sunghoon Kwon, Taesung Park, Sungho Won
Despite the many successes of genome-wide association studies (GWAS), the known susceptibility variants identified by GWAS have modest effect sizes, leading to notable skepticism about the effectiveness of building a risk prediction model from large-scale genetic data. However, in contrast to genetic variants, the family history of diseases has been largely accepted as an important risk factor in clinical diagnosis and risk prediction. Nevertheless, the complicated structures of the family history of diseases have limited their application in clinical practice...
September 12, 2017: Genetics
https://www.readbyqxmd.com/read/28899449/the-provider-perspective-investigating-the-effect-of-the-electronic-patient-reported-outcome-epro-mobile-application-and-portal-on-primary-care-provider-workflow
#14
Parminder K Hans, Carolyn Steele Gray, Ashlinder Gill, James Tiessen
Aim This qualitative study investigates how the Electronic Patient-Reported Outcome (ePRO) mobile application and portal system, designed to capture patient-reported measures to support self-management, affected primary care provider workflows. BACKGROUND: The Canadian health system is facing an ageing population that is living with chronic disease. Disruptive innovations like mobile health technologies can help to support health system transformation needed to better meet the multifaceted needs of the complex care patient...
September 13, 2017: Primary Health Care Research & Development
https://www.readbyqxmd.com/read/28893894/fees-for-medical-liability-protection-decrease-in-populous-regions
#15
Roger Collier
No abstract text is available yet for this article.
September 11, 2017: CMAJ: Canadian Medical Association Journal, Journal de L'Association Medicale Canadienne
https://www.readbyqxmd.com/read/28893881/cma-votes-for-review-of-medical-liability-system
#16
Roger Collier
No abstract text is available yet for this article.
September 11, 2017: CMAJ: Canadian Medical Association Journal, Journal de L'Association Medicale Canadienne
https://www.readbyqxmd.com/read/28893562/positive-allosteric-modulation-of-m1-and-m4-muscarinic-receptors-as-potential-therapeutic-treatments-for-schizophrenia
#17
REVIEW
Samantha E Yohn, P Jeffrey Conn
Current antipsychotic drugs provide symptomatic relief for positive symptoms of schizophrenia, but do not offer symptom management for negative and cognitive symptoms. In addition, many patients discontinue treatment due to adverse side effects. Therefore, there is a critical need to develop more effective and safe treatment options. Although the etiology of schizophrenia is unclear, considerable data from post-mortem, neuroimaging and neuropharmacology studies support a role of the muscarinic acetylcholine (mAChRs) in the pathophysiology of schizophrenia...
September 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28892629/development-of-4-cyanophenyl-glycine-derivatives-as-reversible-inhibitors-of-lysine-specific-demethylase-1
#18
Daniel P Mould, Cristina Alli, Ulf Bremberg, Sharon Cartic, Allan M Jordan, Matthis Geitmann, Alba Maiques-Diaz, Alison E McGonagle, Tim C P Somervaille, Gary J Spencer, Fabrice Turlais, Donald J Ogilvie
Inhibition of lysine specific demethylase 1 (LSD1) has been shown to induce the differentiation of leukemia stem cells in acute myeloid leukaemia (AML). Irreversible inhibitors developed from the non-specific inhibitor tranylcypromine have entered clinical trials; however, the development of effective reversible inhibitors has proved more challenging. Herein, we describe our efforts to identify reversible inhibitors of LSD1 from a high throughput screen, and subsequent in silico modelling approaches. From a single hit (12) validated by biochemical and biophysical assays, we describe our efforts to develop acyclic scaffold-hops from GSK-690 (1)...
September 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28891358/defensive-medicine-among-obstetricians-and-gynaecologists-in-turkey
#19
Mert Küçük
In recent years, there has been a remarkable increase in medical malpractice litigations against OB/GYNs in Turkey and globally. This high litigation atmosphere may have changed attitudes, behaviour and practice of OB/GYNs. In the current study, opinions and attitudes of OB/GYNs regarding defensive medicine and to what extent they practice it were investigated. One hundred and eight OB/GYNs participated in the study. All participants found obstetrics and gynaecology riskier when compared with other medical branches and reported that they were increasingly practising defensive medicine...
September 11, 2017: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28889212/cocaine-like-discriminative-stimulus-effects-of-norepinephrine-preferring-monoamine-releasers-time-course-and-interaction-studies-in-rhesus-monkeys
#20
Stephen J Kohut, David S Jacobs, Richard B Rothman, John S Partilla, Jack Bergman, Bruce E Blough
RATIONALE: The therapeutic potential of monoamine releasers with prominent dopaminergic effects is hindered by their high abuse liability. OBJECTIVES: The present study examined the effects of several novel "norepinephrine (NE)-preferring" monoamine releasers relative to non-selective monoamine releasers, d-amphetamine and d-methamphetamine, in rhesus monkeys trained to discriminate cocaine. NE-preferring releasers were approximately 13-fold more potent for NE compared to dopamine release and ranged in potency for serotonin release (PAL-329 < l-methamphetamine < PAL-169)...
September 9, 2017: Psychopharmacology
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