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L Pelligand, A Soubret, J N King, J Elliott, J P Mochel
The objective of this study was to model the pharmacokinetics (PKs) of robenacoxib in cats using a nonlinear mixed-effects (NLME) approach, leveraging all available information collected from cats receiving robenacoxib s.c. and/or i.v.: 47 densely sampled laboratory cats and 36 clinical cats sparsely sampled preoperatively. Data from both routes were modeled sequentially using Monolix 4.3.2. Influence of parameter correlations and available covariates (age, gender, bodyweight, and anesthesia) on population parameter estimates were evaluated by using multiple samples from the posterior distribution of the random effects...
October 22, 2016: CPT: Pharmacometrics & Systems Pharmacology
Hisham Hussan, Peter P Stanich, Darrell M Gray, Somashekar G Krishna, Kyle Porter, Darwin L Conwell, Steven K Clinton
BACKGROUND: Morbid obesity is associated with worse colorectal cancer (CRC) perioperative outcomes. The impact of bariatric surgery on these outcomes is unknown. METHODS: The National Inpatient Sample Database (2006-2012) was used to identify adults with prior bariatric surgery (divided into BMI ≤35 kg/m(2) and BMI >35 kg/m(2)) or morbid obesity that underwent CRC surgery. Main outcomes were mortality, surgical complications and health care utilization. RESULTS: There were 1813 patients with prior bariatric surgery and 22,552 morbidly obese patients that underwent CRC surgery between 2006 and 2012...
October 21, 2016: Obesity Surgery
Emily R R Burdett, Amanda J Lucas, Daphna Buchsbaum, Nicola McGuigan, Lara A Wood, Andrew Whiten
This study examined whether instrumental and normative learning contexts differentially influence 4- to 7-year-old children's social learning strategies; specifically, their dispositions to copy an expert versus a majority consensus. Experiment 1 (N = 44) established that children copied a relatively competent "expert" individual over an incompetent individual in both kinds of learning context. In experiment 2 (N = 80) we then tested whether children would copy a competent individual versus a majority, in each of the two different learning contexts...
2016: PloS One
Christoph Nowak, Samira Salihovic, Andrea Ganna, Stefan Brandmaier, Taru Tukiainen, Corey D Broeckling, Patrik K Magnusson, Jessica E Prenni, Rui Wang-Sattler, Annette Peters, Konstantin Strauch, Thomas Meitinger, Vilmantas Giedraitis, Johan Ärnlöv, Christian Berne, Christian Gieger, Samuli Ripatti, Lars Lind, Nancy L Pedersen, Johan Sundström, Erik Ingelsson, Tove Fall
Insulin resistance (IR) and impaired insulin secretion contribute to type 2 diabetes and cardiovascular disease. Both are associated with changes in the circulating metabolome, but causal directions have been difficult to disentangle. We combined untargeted plasma metabolomics by liquid chromatography/mass spectrometry in three non-diabetic cohorts with Mendelian Randomization (MR) analysis to obtain new insights into early metabolic alterations in IR and impaired insulin secretion. In up to 910 elderly men we found associations of 52 metabolites with hyperinsulinemic-euglycemic clamp-measured IR and/or β-cell responsiveness (disposition index) during an oral glucose tolerance test...
October 2016: PLoS Genetics
Harry Whitaker, Gonia Jarema
An acerbic footnote in Volume 3 (1818) of the five-volume great work of Franz Joseph Gall and Johann Gaspar Spurzheim, Anatomy and Physiology of the Nervous System in General and of the Brain in Particular with Observations on the Possibility of Understanding the Many Moral and Intellectual Dispositions of Man and Animals by the Configuration of Their Heads, marked the end of the collaboration between Gall, the founder of organologie, and Spurzheim, promoter of phrenology. We discuss the background of this note and the nature of the rift that marked the end of Gall and Spurzheim's collaboration...
October 21, 2016: Journal of the History of the Neurosciences
Heidi Preis, Yael Benyamini
INTRODUCTION: Basic beliefs about birth as a natural and safe or a medical and risky process are central in the decisions on where and how to birth. Despite their importance, they have not been studied separately from other childbirth-related constructs. Our aim was to develop a measure to assess these beliefs. METHOD: Pregnant Israeli women (N = 850, gestational week ≥14) were recruited in women's health centers, in online natural birth forums, and through home midwives...
October 21, 2016: Journal of Psychosomatic Obstetrics and Gynaecology
Maïlys De Sousa Mendes, Gabrielle Lui, Yi Zheng, Claire Pressiat, Deborah Hirt, Elodie Valade, Naïm Bouazza, Frantz Foissac, Stephane Blanche, Jean-Marc Treluyer, Saik Urien, Sihem Benaboud
BACKGROUND: Pregnant women and their fetuses are exposed to numerous drugs; however, they are orphan populations with respect to the safety and efficacy of drugs. Therefore, the prediction of maternal and fetal drug exposure prior to administration would be highly useful. METHODS: A physiologically-based pharmacokinetic (PBPK) model for nevirapine, which is metabolized by the cytochrome P450 (CYP) 3A4, 2B6 and 2D6 pathways, was developed to predict maternal and fetal pharmacokinetics (PK)...
October 21, 2016: Clinical Pharmacokinetics
Shearwood McClelland, Joseph F Baker, Justin S Smith, Breton G Line, Thomas J Errico, Christopher P Ames, R Shay Bess
Parkinson's disease (PD) is a neurodegenerative disorder manifesting over time to result in reduced mobility. The impact of PD on spinal fusion has yet to be addressed on a nationwide level. The Nationwide Inpatient Sample (NIS) from 2001 to 2012 was used for analysis. Admissions with spinal fusion of two or more vertebrae (ICD-9 codes=81.62, 81.63 and 81.64) were included and then stratified based on the presence or absence of PD (ICD-9 code=332.0); patients with cancer (ICD-9 codes=140-239) or trauma (ICD-9 codes=805...
October 17, 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Amy R Reed
This article analyzes narrative illustrations in genetic counseling textbooks as a way of understanding professional habitus--the dispositions that motivate professional behavior. In particular, this analysis shows that there are significant differences in how the textbooks' expository and narrative portions represent Down syndrome, genetic counseling practice, and patient behaviors. While the narrative portions of the text position the genetic counseling profession as working in service to the values of genetic medicine, the expository portions represent genetic counselors as neutral parties...
October 19, 2016: Journal of Medical Humanities
Aharon Nachshon, Hanifa J Abu-Toamih Atamni, Yael Steuerman, Roa'a Sheikh-Hamed, Alexandra Dorman, Richard Mott, Juliane C Dohm, Hans Lehrach, Marc Sultan, Ron Shamir, Sascha Sauer, Heinz Himmelbauer, Fuad A Iraqi, Irit Gat-Viks
A central challenge in pharmaceutical research is to investigate genetic variation in response to drugs. The Collaborative Cross (CC) mouse reference population is a promising model for pharmacogenomic studies because of its large amount of genetic variation, genetic reproducibility, and dense recombination sites. While the CC lines are phenotypically diverse, their genetic diversity in drug disposition processes, such as detoxification reactions, is still largely uncharacterized. Here we systematically measured RNA-sequencing expression profiles from livers of 29 CC lines under baseline conditions...
2016: Frontiers in Genetics
Jia Yin, Haichuan Duan, Joanne Wang
Renal transporter-mediated drug-drug interactions (DDIs) are of significant clinical concerns as they can adversely impact drug disposition, efficacy and toxicity. Emerging evidence suggests that human renal organic cation transporter 2 (hOCT2) and multidrug and toxin extrusion proteins 1 and 2-K (hMATE1/2-K) exhibit substrate-dependent inhibition but the impact on renal drug secretion and intracellular accumulation is unknown. Using metformin and atenolol as the probe substrates, we found that the classic inhibitors (e...
October 6, 2016: Journal of Pharmacology and Experimental Therapeutics
T A Lewandowski
Carisoprodol is a widely prescribed muscle relaxant and is also a drug known to be a subject to abuse. Despite the fact that carisoprodol has been available for prescription since 1959, a number of gaps in our knowledge of the toxicokinetics of this common drug exist. For example, the volume of distribution (Vd) for carisoprodol in humans has not been reported. A two-compartment pharmacokinetic model describing carisoprodol metabolism and that of the primary metabolite, meprobamate, was developed to better understand the pharmacokinetics of this drug...
October 10, 2016: Human & Experimental Toxicology
J Pakpoor, D Saylor, I Izbudak, L Liu, E M Mowry, D M Yousem
BACKGROUND AND PURPOSE: The increasing use of the emergency department MR imaging scanner at our institution raises questions about its added value to certain patient groups. We hypothesized that the use of emergency department MR imaging for identifying active demyelination in MS patients presenting with new neurologic symptoms would be of low yield. MATERIALS AND METHODS: Electronic medical records were reviewed for patients with MS who had emergency department MR imaging scans for a suspected MS exacerbation between March 1, 2014, and March 1, 2016...
October 6, 2016: AJNR. American Journal of Neuroradiology
Ming Li, Inge A M de Graaf, Marina H de Jager, Geny M M Groothuis
Although intestinal P-glycoprotein (P-gp) has been extensively studied in vitro and in animals, its activity and the consequences of P-gp inhibition for drug disposition and toxicity in humans are still difficult to accurately extrapolate from these studies. Moreover, existing in vitro models do not take into consideration that the intestine is heterogeneous with respect to P-gp expression. Recently, we reported rat precision-cut intestinal slices (PCIS) as a physiological ex vivo model to study the regional gradient of P-gp activity and inhibition...
October 19, 2016: Biopharmaceutics & Drug Disposition
Michel Debacker, Filip Van Utterbeeck, Christophe Ullrich, Erwin Dhondt, Ives Hubloue
It is recognized that the study of the disaster medical response (DMR) is a relatively new field. To date, there is no evidence-based literature that clearly defines the best medical response principles, concepts, structures and processes in a disaster setting. Much of what is known about the DMR results from descriptive studies and expert opinion. No experimental studies regarding the effects of DMR interventions on the health outcomes of disaster survivors have been carried out. Traditional analytic methods cannot fully capture the flow of disaster victims through a complex disaster medical response system (DMRS)...
December 2016: Journal of Medical Systems
Xiaodong Yue, Feng Jiang, Su Lu, Neelam Hiranandani
Humor seems to manifest differently in Western and Eastern cultures, although little is known about how culture shapes humor perceptions. The authors suggest that Westerners regard humor as a common and positive disposition; the Chinese regard humor as a special disposition particular to humorists, with controversial aspects. In Study 1, Hong Kong participants primed with Western culture evaluate humor more positively than they do when primed with Chinese culture. In Study 2a, Canadians evaluate humor as being more important in comparison with Chinese participants...
2016: Frontiers in Psychology
Chengxiang Tang, Judy Xu, Meng Zhang
BACKGROUND: Public health care dominated the services provision in China before 1980s. However, the number of private health care providers in China has been increasing since then. The growth of private hospitals escalated after a market-oriented reform was implemented in 2001. Through an experimental approach, this study aims to a better understanding of the dynamic change in preference of health care utilisation among the residents in urban China. METHODS: Based on a discrete choice experiment (DCE) from a random sample of respondents in urban China, the study evaluated preference over health care attributes affecting individuals' choice for the utilisation of hospital health care...
October 18, 2016: BMC Health Services Research
Michael S Toce, Michele M Burns, Katherine A O'Donnell
CONTEXT: Exploratory buprenorphine ingestions in young children have been associated with clinically significant toxicity. However, detailed data on the clinical presentation and management of these patients are lacking. In an attempt to obtain more comprehensive data, we sought to examine a single center cohort of patients with report of buprenorphine exposure and provide descriptive analysis of rates of respiratory depression, time to respiratory depression, interventions, disposition, and outcomes...
October 19, 2016: Clinical Toxicology
Yann-Leei Larry Lee, Kaci D Sims, Charles C Butts, M Amin Frotan, Steven Kahn, Sidney B Brevard, Jon D Simmons
There are few published reports on the unique nature of burn patients using a paired spontaneous awakening and spontaneous breathing protocol. A combined protocol was implemented in our burn intensive care unit (ICU) on January 1, 2012. This study evaluates the impact of this protocol on patient outcomes in a burn ICU. We performed a retrospective review of our burn registry over 4 years, including all patients placed on mechanical ventilation. In the latter 2 years, patients meeting criteria underwent daily spontaneous awakening trial; if successful, spontaneous breathing trial was performed...
October 6, 2016: Journal of Burn Care & Research: Official Publication of the American Burn Association
Y K Lyauk, C Stage, T K Bergmann, L Ferrero-Milliani, D Bjerre, R Thomsen, K P Dalhoff, H B Rasmussen, G Jürgens
The aim of this study was to identify demographic and genetic factors that significantly affect methylphenidate (MPH) pharmacokinetics (PK), and may help explain interindividual variability and further increase the safety of MPH. d-MPH plasma concentrations, demographic covariates, and carboxylesterase 1 (CES1) genotypes were gathered from 122 healthy adults and analyzed using nonlinear mixed effects modeling. The structural model that best described the data was a two-compartment disposition model with absorption transit compartments...
October 18, 2016: Clinical and Translational Science
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