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https://www.readbyqxmd.com/read/28636309/quantitative-chemical-proteomic-profiling-of-the-in-vivo-targets-of-reactive-drug-metabolites
#1
Landon R Whitby, R Scott Obach, Gabriel M Simon, Matthew M Hayward, Benjamin F Cravatt
Idiosyncratic liver toxicity represents an important problem in drug research and pharmacotherapy. Reactive drug metabolites that modify proteins are thought to be a principal factor in drug-induced liver injury. Here, we describe a quantitative chemical proteomic method to identify the targets of reactive drug metabolites in vivo. Treating mice with clickable analogues of four representative hepatotoxic drugs, we demonstrate extensive covalent binding that is confined primarily to the liver. Each drug exhibited a distinct target profile that, in certain cases, showed strong enrichment for specific metabolic pathways (e...
June 21, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28628631/computational-explanation-for-bioactivation-mechanism-of-targeted-anticancer-agents-mediated-by-cytochrome-p450s-a-case-of-erlotinib
#2
Chun-Zhi Ai, Yong Liu, Wei Li, De-Meng Chen, Xin-Xing Zhu, Ya-Wei Yan, Du-Chu Chen, Yi-Zhou Jiang
EGFR inhibitors, even with therapeutics superiorities in anticancer, can cause idiosyncratic pulmonary and hepatic toxicities that are associated with the reactive electrophile bioactivated by Cytochrome P450s (P450s). Until now, neither has the electrophilic intermediate been caught experimentally, nor has the subtle mechanism been declared. Herein, the underlying mechanism of bioactivation mediated by P450s was explored by DFT calculations for a case of EGFR inhibitor, Erlotinib. Based on the calculation and analysis, we suggest that with other metabolites, reactive electrophiles of Erlotinib: epoxide and quinine-imine, can be generated by several steps along the oxidative reaction pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28624720/retention-of-perampanel-in-adults-with-pharmacoresistant-epilepsy-at-a-single-tertiary-care-center
#3
Tim Wehner, Shahidul Mannan, Sanchit Turaga, Kirtana Vallabhaneni, Hao Meng Yip, Carys Wiggans, Rohit Shankar, John S Duncan, Josemir W Sander
RATIONALE: Observational data on antiepileptic drugs (AEDs) inform about their use in clinical practice. We describe our clinical experience with perampanel (PER) in a large UK tertiary epilepsy center. METHODS: Adults initiated on PER between October 2012 and March 2015 were followed until they discontinued PER or 10 September 2016. Data on epilepsy syndrome, duration, seizure types, concomitant and previous AED use, PER dosing, efficacy and side effects were recorded...
June 15, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28618493/simple-wealth-distribution-model-causing-inequality-induced-crisis-without-external-shocks
#4
Henri Benisty
We address the issue of the dynamics of wealth accumulation and economic crisis triggered by extreme inequality, attempting to stick to most possibly intrinsic assumptions. Our general framework is that of pure or modified multiplicative processes, basically geometric Brownian motions. In contrast with the usual approach of injecting into such stochastic agent models either specific, idiosyncratic internal nonlinear interaction patterns or macroscopic disruptive features, we propose a dynamic inequality model where the attainment of a sizable fraction of the total wealth by very few agents induces a crisis regime with strong intermittency, the explicit coupling between the richest and the rest being a mere normalization mechanism, hence with minimal extrinsic assumptions...
May 2017: Physical Review. E
https://www.readbyqxmd.com/read/28616438/drug-reaction-with-eosinophilia-and-systemic-symptom-in-a-patient-with-pneumonia-and-hyperthyroidism
#5
Hualiang Jin, Limin Wang, Jian Ye
Drug rash with eosinophilia and systemic symptoms syndrome is an idiosyncratic drug reaction characterized by fever, skin eruption, lymph node enlargement, and internal organ involvement. We report a case of a patient with pneumonia who developed clinical manifestations of fever, rash, lymphadenopathy, hypereosinophilia, and visceral involvement (renal failure and eosinophilic pneumonitis) caused by methimazole. The patient improved remarkably with drug withdrawal. A high index of clinical suspicion is emphasized to facilitate prompt diagnosis of medication-related adverse effect and its discontinuation...
April 2017: Journal of Research in Pharmacy Practice
https://www.readbyqxmd.com/read/28616200/season-modulated-responses-of-neotropical-bats-to-forest-fragmentation
#6
Diogo F Ferreira, Ricardo Rocha, Adrià López-Baucells, Fábio Z Farneda, João M B Carreiras, Jorge M Palmeirim, Christoph F J Meyer
Seasonality causes fluctuations in resource availability, affecting the presence and abundance of animal species. The impacts of these oscillations on wildlife populations can be exacerbated by habitat fragmentation. We assessed differences in bat species abundance between the wet and dry season in a fragmented landscape in the Central Amazon characterized by primary forest fragments embedded in a secondary forest matrix. We also evaluated whether the relative importance of local vegetation structure versus landscape characteristics (composition and configuration) in shaping bat abundance patterns varied between seasons...
June 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28615505/topological-features-of-a-gene-co-expression-network-predict-patterns-of-natural-diversity-in-environmental-response
#7
David L Des Marais, Rafael F Guerrero, Jesse R Lasky, Samuel V Scarpino
Molecular interactions affect the evolution of complex traits. For instance, adaptation may be constrained by pleiotropic or epistatic effects, both of which can be reflected in the structure of molecular interaction networks. To date, empirical studies investigating the role of molecular interactions in phenotypic evolution have been idiosyncratic, offering no clear patterns. Here, we investigated the network topology of genes putatively involved in local adaptation to two abiotic stressors-drought and cold-in Arabidopsis thaliana Our findings suggest that the gene-interaction topologies for both cold and drought stress response are non-random, with genes that show genetic variation in drought expression response (eGxE) being significantly more peripheral and cold response genes being significantly more central than genes which do not show GxE...
June 14, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/28612953/eye-movements-sensori-motor-adaptation-and-cerebellar-dependent-learning-in-autism-towards-potential-biomarkers-and-sub-phenotypes
#8
Edward G Freedman, John J Foxe
Because of the wide range of symptoms expressed in individuals with Autism Spectrum Disorder (ASD) and their idiosyncratic severity it is unlikely that a single remedial approach will be universally effective. Resolution of this dilemma requires identifying subgroups within the autism spectrum, based on symptom set and severity, on an underlying neuro-structural difference, and on specific behavioral dysfunction. This will provide critical insight into the disorder and may lead to better diagnoses, and more targeted remediation in these subphenotypes of people with ASD...
June 14, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28604284/thermal-performance-curves-and-the-metabolic-theory-of-ecology-a-practical-guide-to-models-and-experiments-for-parasitologists
#9
Péter K Molnár, Jason P Sckrabulis, Karie A Altman, Thomas R Raffel
Climate change will affect host-parasite dynamics in complex ways. The development of forecast models is necessary for proactive disease management, but past studies frequently reported thermal performance data in idiosyncratic ways that have limited use for parameterizing thermal host-parasite models. Developing improved forecast models will require strong collaborations between experimental parasitologists and disease modelers. The purpose of this article is to facilitate such collaborations by reviewing practical considerations for describing thermal performance curves of parasite and host performance traits, and using them to predict climate change impacts on host-parasite systems...
June 6, 2017: Journal of Parasitology
https://www.readbyqxmd.com/read/28599553/between-speaker-variability-in-temporal-organizations-of-intensity-contours
#10
Lei He, Volker Dellwo
Intensity contours of speech signals were sub-divided into positive and negative dynamics. Positive dynamics were defined as the speed of increases in intensity from amplitude troughs to subsequent peaks, and negative dynamics as the speed of decreases in intensity from peaks to troughs. Mean, standard deviation, and sequential variability were measured for both dynamics in each sentence. Analyses showed that measures of both dynamics were separately classified and between-speaker variability was largely explained by measures of negative dynamics...
May 2017: Journal of the Acoustical Society of America
https://www.readbyqxmd.com/read/28599013/thumb-rest-position-and-its-role-in-neuromuscular-control-of-the-clarinet-task
#11
Kathryn E Young, Sara A Winges
Musicians spend long hours of practice and performance to master their instrument. Clarinet players support their roughly 2-lb instrument on the right-hand thumb, which results in cumulative static loading of the arm. This posture in turn can cause discomfort and, in some cases, evolve into debilitating overuse injuries and pain throughout the right upper limb. Altering the thumb-rest position has been proposed as a way to alleviate this discomfort, although no quantitative research has been conducted on this issue...
June 2017: Medical Problems of Performing Artists
https://www.readbyqxmd.com/read/28594194/conducting-preference-assessments-for-youth-with-disorders-of-consciousness-during-rehabilitation
#12
Adrianna Amari, Stacy J Suskauer, Valerie Paasch, Lauren K Grodin, Beth S Slomine
PURPOSE: Care and rehabilitation for individuals with disorders of consciousness (DOC) can be challenging; the use of observational data collection, individualized treatment programs, and incorporation of preferred, personally meaningful and salient items may be helpful in addressing such challenges during assessment and intervention. In this article, we extend the predominantly adult literature on use of salient items to promote differential responding by describing our methodology to identify preferred items across sensory domains for application during inpatient rehabilitation with children with DOC...
June 8, 2017: Rehabilitation Psychology
https://www.readbyqxmd.com/read/28572356/idiosyncratic-desires
#13
Erika Lorraine Milam
No abstract text is available yet for this article.
June 2, 2017: Science
https://www.readbyqxmd.com/read/28571510/panacea-or-diagnosis-imaginaries-of-innovation-and-the-mit-model-in-three-political-cultures
#14
Sebastian Pfotenhauer, Sheila Jasanoff
Innovation studies continue to struggle with an apparent disconnect between innovation's supposedly universal dynamics and a sense that policy frameworks and associated instruments of innovation are often ineffectual or even harmful when transported across regions or countries. Using a cross-country comparative analysis of three implementations of the 'MIT model' of innovation in the UK, Portugal and Singapore, we show how key features in the design, implementation and performance of the model cannot be explained as mere variations on an identical solution to the same underlying problem...
May 1, 2017: Social Studies of Science
https://www.readbyqxmd.com/read/28553995/mapping-regulatory-models-for-medicinal-cannabis-a-matrix-of-options
#15
Vendula Belackova, Marian Shanahan, Alison Ritter
Objective The aim of the present study was to develop a framework for assessing regulatory options for medicinal cannabis in Australia.Methods International regulatory regimes for medicinal cannabis were reviewed with a qualitative policy analysis approach and key policy features were synthesised, leading to a conceptual framework that facilitates decision making across multiple dimensions.Results Two central organising dimensions of medicinal cannabis regulation were identified: cannabis supply and patient authorisation (including patient access)...
May 30, 2017: Australian Health Review: a Publication of the Australian Hospital Association
https://www.readbyqxmd.com/read/28553770/involvement-of-reactive-metabolites-of-diclofenac-in-cytotoxicity-in-sandwich-cultured-rat-hepatocytes
#16
Atsushi Kawase, Ryota Hashimoto, Mai Shibata, Hiroaki Shimada, Masahiro Iwaki
BACKGROUND AND OBJECTIVES: Diclofenac (DIC) is metabolized to reactive metabolites such as diclofenac acyl-β-d-glucuronide (DIC-AG). It is possible that such reactive metabolites could cause tissue damage by formation of covalent protein adducts and other modification of cellular proteins or by induction of immune responses against its covalent protein adducts. However, the detailed mechanisms of idiosyncratic drug-induced liver injury (DILI) have been unclear. The objective is to clarify the involvement of DIC-AG and 4'hydroxydiclofenac (4'OH-DIC) in acute DILI...
May 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/28549354/the-facespan-the-perceptual-span-for-face-recognition
#17
Michael Papinutto, Junpeng Lao, Meike Ramon, Roberto Caldara, Sébastien Miellet
In reading, the perceptual span is a well-established concept that refers to the amount of information that can be read in a single fixation. Surprisingly, despite extensive empirical interest in determining the perceptual strategies deployed to process faces and an ongoing debate regarding the factors or mechanism(s) underlying efficient face processing, the perceptual span for faces-the Facespan-remains undetermined. To address this issue, we applied the gaze-contingent Spotlight technique implemented in an old-new face recognition paradigm...
May 1, 2017: Journal of Vision
https://www.readbyqxmd.com/read/28535408/differences-in-clinical-and-cognitive-variables-in-seasonal-affective-disorder-compared-to-depressive-related-disorders-evidence-from-a-population-based-study-in-finland
#18
I Morales-Muñoz, S Koskinen, T Partonen
BACKGROUND: Seasonal affective disorder (SAD) is a type of depression with seasonal pattern. Although it involves some idiosyncratic symptoms, it can overlap with other depressive disorders such as major depressive disorder (MDD) or dysthymia. We aimed to characterize the differences in specific cognitive and clinical symptoms between SAD and depressive-related disorders. METHODS: In total, 4554 Finnish subjects from the population-based Health 2011 Survey were interviewed with the Munich version of Composite International Diagnostic Interview (M-CIDI) and filled in the Seasonal Pattern Assessment Questionnaire (SPAQ)...
March 28, 2017: European Psychiatry: the Journal of the Association of European Psychiatrists
https://www.readbyqxmd.com/read/28535071/aphasia-from-the-inside-the-cognitive-world-of-the-aphasic-patient
#19
Alfredo Ardila, Silvia Rubio-Bruno
The purpose of this study was to analyze the question: how do people with aphasia experience the world? Three questions are approached: (1) how is behavior controlled in aphasia, considering that a normal linguistic control is no longer available; (2) what is the pattern of intellectual abilities in aphasia; and (3) what do aphasia patients' self-report regarding the experience of living without language. In aphasia, behavior can no longer be controlled through the "second signal system" and only the first signal system remains...
May 23, 2017: Applied Neuropsychology. Adult
https://www.readbyqxmd.com/read/28533580/olanzapine-induced-neuroleptic-malignant-syndrome
#20
Seyedhamze Hosseini, Forouzan Elyasi
Neuroleptic malignant syndrome (NMS) is a rare but life-threatening idiosyncratic side effect resulting from neuroleptic drugs. NMS mainly occurs in patients treated with high-potency typical antipsychotics, but rarely caused by atypical antipsychotics. Although NMS is less common with atypical antipsychotic, but it seems that its incidence is rising due to increased administration of such drugs. We present the case of a 27-year-old man with a history of paranoid schizophrenia that showed signs consistent with NMS that occurred after treatment with olanzapine...
May 2017: Iranian Journal of Medical Sciences
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