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https://www.readbyqxmd.com/read/28437834/elucidation-of-factor-viii-activity-pharmacokinetics-a-pooled-population-analysis-in-hemophilia-a-patients-treated-with-moroctocog-alfa
#1
João A Abrantes, Elisabet I Nielsen, Joan Korth-Bradley, Lutz Harnisch, Siv Jönsson
This study investigated the disposition of coagulation factor VIII activity in 754 moderate to severe hemophilia A patients following the administration of moroctocog alfa, a B-domain deleted recombinant factor VIII. Data analyzed included patients aged 1 day to 73 years enrolled in 13 studies conducted over a period of 20 years in 25 countries. A two-compartment population pharmacokinetic model with a baseline model described the pooled data well. Body size, age, inhibitors, race and analytical assay were identified as significant predictors of factor VIII disposition...
April 24, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28437104/redox-active-macrocycles-for-organic-rechargeable-batteries
#2
Dong Jun Kim, Keith R Hermann, Aleksandrs Prokofjevs, Michael T Otley, Cristian Pezzato, Magdalena Owczarek, J Fraser Stoddart
Organic rechargeable batteries, composed of redox-active molecules, are emerging as candidates for the next generation of energy storage materials because of their large specific capacities, cost effectiveness, and the abundance of organic precursors, when compared with conventional lithium-ion batteries. Although redox-active molecules often display multiple redox states, precise control of a molecule's redox potential, leading to a single output voltage in a battery, remains a fundamental challenge in this popular field of research...
April 24, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28436739/prediabetes-exhibits-decreased-disposition-index-correlated-with-deterioration-of-glycemic-parameters-in-nonobese-japanese-subjects-a-cross-sectional-study-from-medical-examination
#3
Yasutaka Takeda, Yukihiro Fujita, Tsuyoshi Yanagimachi, Jun Honjo, Atsuko Abiko, Mahito Asai, Masakazu Haneda
BACKGROUND: Prediabetes, defined as impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), likely develops to type 2 diabetes mellitus (DM) and independently increases cardiovascular risk. We employed disposition index (DI), a new metabolic parameter indicating the pancreatic beta cell function adjusted for insulin resistance, and investigated whether it could be altered in Japanese population with prediabetes and associated with early glucose intolerance. METHODS: A total of 102 adults who underwent an oral glucose tolerance test at the medical screening were designated to normal glucose tolerance (NGT), IFG, IGT, and DM...
April 24, 2017: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/28436712/disposition-and-metabolism-of-14-c-galunisertib-a-tgf-%C3%AE-ri-kinase-alk5-inhibitor-following-oral-administration-in-healthy-subjects-and-mechanistic-prediction-of-the-effect-of-itraconazole-on-galunisertib-pharmacokinetics
#4
Kenneth C Cassidy, Ivelina Gueorguieva, Colin Miles, Jessica Rehmel, Ping Yi, William J Ehlhardt
The disposition and metabolism of galunisertib (LY2157299 monohydrate, a TGF-βRI Kinase/ALK5 Inhibitor) was characterized following a single oral dose of 150 mg of [(14)C]-galunisertib (100 µCi) to six healthy human subjects. The galunisertib plasma half-life was 8.6 h, while the (14)C half-life was 10.0 h. Galunisertib was abundant in circulation (40.3% of the (14)C AUC0-24h), with 7 additional metabolites detected in plasma. Two metabolites LSN3199597 (M5, mono-oxidation), and M4 (glucuronide of M3) were the most abundant circulating metabolites (10...
April 24, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28435896/association-between-persistent-tachycardia-and-tachypnea-and-in-hospital-mortality-among-non-hypotensive-emergency-department-patients-admitted-to-the-hospital
#5
Michael A Puskarich, Utsav Nandi, Ben G Long, Alan E Jones
OBJECTIVE: Vital sign trends are used in clinical practice to assess treatment response and aid in disposition, yet quantitative data to support this practice are lacking. This study aimed to determine the prognostic value of vital sign normalization. METHODS: Secondary analysis of a prospective cohort of adult emergency department (ED) patients admitted a single urban tertiary care hospital. A random sample of 182 days was chosen, and a manual review of all admissions was undertaken...
March 2017: Clinical and Experimental Emergency Medicine
https://www.readbyqxmd.com/read/28435710/inter-action-between-maleic-acid-and-n-r-furfuryl-amines-crystal-structure-of-2-methyl-n-5-phenyl-furan-2-yl-meth-yl-propan-2-aminium-2z-3-carb-oxy-acrylate-and-n-5-iodo-furan-2-yl-meth-yl-2-methyl-propan-2-aminium-2z-3-carb-oxy-prop-2-enoate
#6
Elisaveta A Kvyatkovskaya, Vladimir P Zaytsev, Fedor I Zubkov, Pavel V Dorovatovskii, Yan V Zubavichus, Victor N Khrustalev
The title mol-ecular salts, C15H20NO(+)·C4H3O4(-), (I), and C9H15INO(+)·C4H3O4(-), (II), have very similar mol-ecular geometries for both cation and anion. The anions of both (I) and (II) are practically planar (r.m.s. deviations = 0.062 and 0.072 Å, respectively) and adopt a rare symmetrical geometry with the hy-droxy H atom approximately equidistant from the two O atoms. In their crystals, the cations and anions in both (I) and (II) form tight ionic pairs via strong N-H⋯O hydrogen bonds, with a roughly perpendicular disposition of the anion to the furan ring of the cation...
April 1, 2017: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/28435497/improved-accuracy-and-quality-of-information-during-emergency-department-care-transitions
#7
Nnaemeka Okafor, Justin Mazzillo, Sara Miller, Kimberly A Chambers, Samar Yusuf, Vanessa Garza-Miranda, Yashwant Chathampally
INTRODUCTION: Suboptimal communication during emergency department (ED) care transitions has been shown to contribute to medical errors, sometimes resulting in patient injury and litigation. The study objective was to determine whether a standardized checkout process would decrease the number of relevant missed clinical items (MCI). METHODS: In this prospective pre- and post-intervention study conducted in an urban academic ED, we collected data on omitted or inaccurately conveyed medical information before and after the initiation of a standardized checkout process...
April 2017: Western Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28435487/randomized-trial-of-adding-parenteral-acetaminophen-to-prochlorperazine-and-diphenhydramine-to-treat-headache-in-the-emergency-department
#8
Stefan H Meyering, Ryan W Stringer, Matthew K Hysell
INTRODUCTION: Headaches represent over three million emergency department (ED) visits per year, comprising 2.4% of all ED visits. There are many proposed methods and clinical guidelines of treating acute headache presentations. However, data on intravenous acetaminophen usage in these settings are lacking. In this study, we sought to determine the efficacy of intravenous (IV) acetaminophen as an adjunct to a standard therapy for the treatment of patients who present to the ED with a chief complaint of "headache...
April 2017: Western Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28434102/outcomes-following-surgical-management-of-cauda-equina-syndrome-does-race-matter
#9
Amit Jain, Emmanuel Menga, Addisu Mesfin
Cauda equina syndrome (CES) is a surgical emergency requiring urgent spinal decompression. Our objective is to analyze the association between race and in-hospital outcomes (complications, mortality, length of stay, and discharge disposition) in patients with CES. This is a retrospective cohort study of CES patients identified via the Nationwide Inpatient Sample (NIS) from 2000 to 2010 in inpatient hospitalizations in the USA. The patient sample includes 46,017 patients ≥18 undergoing spine surgery for CES...
April 21, 2017: Journal of Racial and Ethnic Health Disparities
https://www.readbyqxmd.com/read/28433749/novel-sulphur-containing-imatinib-metabolites-found-by-untargeted-lc-hrms-analysis
#10
Ivo Vrobel, David Friedecký, Edgar Faber, Lukáš Najdekr, Kateřina Mičová, Radana Karlíková, Tomáš Adam
Untargeted metabolite profiling using high-resolution mass spectrometry coupled with liquid chromatography (LC-HRMS), followed by data analysis with the Compound Discoverer 2.0™ software, was used to study the metabolism of imatinib in humans with chronic myeloid leukemia. Plasma samples from control (drug-free) and patient (treated with imatinib) groups were analyzed in full-scan mode and the unknown ions occurring only in the patient group were then, as potential imatinib metabolites, subjected to multi-stage fragmentation in order to elucidate their structure...
April 19, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28433428/effect-of-risk-acceptance-for-bundled-care-payments-on-clinical-outcomes-in-a-high-volume-total-joint-arthroplasty-practice-after-implementation-of-a-standardized-clinical-pathway
#11
James R Kee, Paul K Edwards, Charles L Barnes
BACKGROUND: The Bundled Payments for Care Improvement (BPCI) initiative and the Arkansas Payment Improvement (API) initiative seek to incentivize reduced costs and improved outcomes compared with the previous fee-for-service model. Before participation, our practice initiated a standardized clinical pathway (CP) to reduce length of stay (LOS), readmissions, and discharge to postacute care facilities. METHODS: This practice implemented a standardized CP focused on patient education, managing patient expectations, and maximizing cost outcomes...
March 16, 2017: Journal of Arthroplasty
https://www.readbyqxmd.com/read/28433098/wilson-disease-in-children
#12
Eve A Roberts, Piotr Socha
Wilson disease (WD) is an inherited disorder mainly of hepatocellular copper disposition, due to dysfunction of the Wilson ATPase, a P1B-ATPase encoded by the gene ATP7B. In children, as in older age brackets, clinical disease is highly diverse. Although hepatic disease is the common presentation in children/adolescents, neurologic, psychiatric, and hematologic clinical presentations do occur. Very young children may have clinically evident liver disease due to WD. Early diagnosis, preferably when the child/adolescent is asymptomatic, is most likely to result in near-normal longevity with generally good health so long as the patient tolerates effective medication, is adherent to the lifelong treatment regimen, and has consistent access to the medication...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28431184/congener-specific-disposition-of-chiral-polychlorinated-biphenyls-in-lactating-mice-and-their-offspring-implications-for-pcb-developmental-neurotoxicity
#13
Izabela Kania-Korwel, Tracy Lukasiewicz, Christopher D Barnhart, Marianna Stamou, Haeun Chung, Kevin M Kelly, Stelvio Bandiera, Pamela J Lein, Hans-Joachim Lehmler
Chiral polychlorinated biphenyl (PCB) congeners have been implicated by laboratory and epidemiological studies in PCB developmental neurotoxicity. These congeners are metabolized by cytochrome P450 (P450) enzymes to potentially neurotoxic hydroxylated metabolites (OH-PCBs). The present study explores the enantioselective disposition and toxicity of two environmentally relevant, neurotoxic PCB congeners and their OH-PCB metabolites in lactating mice and their offspring following dietary exposure of the dam. Female C57BL/6N mice (8 weeks old) were fed daily, beginning two weeks prior to conception and continuing throughout gestation and lactation, with 3...
April 14, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28431006/regulation-of-oxidized-platelet-lipidome-implications-for-coronary-artery-disease
#14
Madhumita Chatterjee, Dominik Rath, Jörg Schlotterbeck, Johannes Rheinlaender, Britta Walker-Allgaier, Nada Alnaggar, Monika Zdanyte, Iris Müller, Oliver Borst, Tobias Geisler, Tilman E Schäffer, Michael Lämmerhofer, Meinrad Gawaz
Aims: Hyperlipidaemia enhances susceptibility to thrombosis, while platelet oxidixed LDL (oxLDL) binding in acute coronary syndrome (ACS) correlates with activation status. This study explores the platelet lipidome in symptomatic coronary artery disease (CAD) patients and the functional consequences of the chemokine CXCL12 and its receptors CXCR-4/-7 on lipid uptake in platelets. Methods and results: Platelet-oxLDL detected by flow cytometry was enhanced (P = 0...
April 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28430015/a-randomized-controlled-trial-of-a-mindfulness-and-acceptance-group-therapy-for-residential-substance-use-patients
#15
Ryan C Shorey, Joanna Elmquist, Michael J Gawrysiak, Catherine Strauss, Ellen Haynes, Scott Anderson, Gregory L Stuart
BACKGROUND: Substance use disorders are understood as a chronically relapsing condition that is difficult to treat. However, in recent years there have been promising developments in the treatment of substance use disorders, specifically with interventions based on mindfulness and acceptance and commitment therapy. Little research has examined whether these types of interventions may positively impact residential substance use treatment outcomes. OBJECTIVES: Thus, in the current study we developed and examined, in a randomized controlled trial, a 4-week, eight-session, adjunctive mindfulness and acceptance group therapy for patients in residential substance use treatment...
April 21, 2017: Substance Use & Misuse
https://www.readbyqxmd.com/read/28428365/interaction-and-transport-of-methamphetamine-and-its-primary-metabolites-by-organic-cation-and-multidrug-and-toxin-extrusion-transporters
#16
David J Wagner, Jennifer E Sager, Haichuan Duan, Nina Isoherranen, Joanne Wang
Methamphetamine is one of the most abused illicit drugs with roughly 1.2 million users in the United States alone. A large portion of methamphetamine and its metabolites is eliminated by the kidney with renal clearance larger than glomerular filtration clearance. Yet the mechanism of active renal secretion is poorly understood. The goals of this study were to characterize the interaction of methamphetamine and its major metabolites with organic cation transporters (OCT) and multidrug and toxin extrusion (MATE) transporters and to identify the major transporters involved in the disposition of methamphetamine and its major metabolites, amphetamine and p-hydroxymethamphetamine (p-OHMA)...
April 20, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28422176/the-characteristics-of-newly-diagnosed-adult-early-onset-diabetes-a-population-based-cross-sectional-study
#17
Xiantong Zou, Xianghai Zhou, Linong Ji, Wenying Yang, Juming Lu, Jianping Weng, Weiping Jia, Zhongyan Shan, Jie Liu, Haoming Tian, Qiuhe Ji, Dalong Zhu, Jiapu Ge, Lixiang Lin, Li Chen, Xiaohui Guo, Zhigang Zhao, Qiang Li, Zhiguang Zhou
To investigate the characteristics of newly diagnosed early-onset diabetes in the Chinese population, 2801 newly diagnosed diabetes participants without known diabetes or pre-diabetes in a national cross-sectional survey were analysed. Participants were divided into quartiles (22-43, 44-52, 53-61 and >61 years) according to age of diabetes onset and the first group were defined as early-onset diabetes group. Early-onset diabetes group had lower systolic blood pressure (SBP), total cholesterol, low density lipoprotein cholesterol, 2-hour post prandial blood glucose and urine albumin creatinine ratio...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28421387/pharmacokinetics-of-monoclonal-antibodies-and-fc-fusion-proteins
#18
REVIEW
Liming Liu
There are many factors that can influence the pharmacokinetics (PK) of a mAb or Fc-fusion molecule with the primary determinant being FcRn-mediated recycling. Through Fab or Fc engineering, IgG-FcRn interaction can be used to generate a variety of therapeutic antibodies with significantly enhanced half-life or ability to remove unwanted antigen from circulation. Glycosylation of a mAb or Fc-fusion protein can have a significant impact on the PK of these molecules. mAb charge can be important and variants with pI values of 1-2 unit difference are likely to impact PK with lower pI values being favorable for a longer half-life...
April 19, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28421306/breast-cancer-resistance-protein-and-multidrug-resistance-protein-2-regulate-the-disposition-of-acacetin-glucuronides
#19
Huangyu Jiang, Jia Yu, Haihui Zheng, Jiamei Chen, Jinjun Wu, Xiaoxiao Qi, Ying Wang, Xinchun Wang, Ming Hu, Lijun Zhu, Zhongqiu Liu
PURPOSE: To determine the mechanism responsible for acacetin glucuronide transport and the bioavailability of acacetin. METHODS: Area under the curve (AUC), clearance (CL), half-life (T1/2) and other pharmacokinetic parameters were determined by the pharmacokinetic model. The excretion of acacetin glucuronides was evaluated by the mouse intestinal perfusion model and the Caco-2 cell model. RESULTS: In pharmacokinetic studies, the bioavailability of acacetin in FVB mice was 1...
April 18, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28421020/social-dominance-orientation-dispositional-empathy-and-need-for-cognitive-closure-moderate-the-impact-of-empathy-skills-training-but-not-patient-contact-on-medical-students-negative-attitudes-toward-higher-weight-patients
#20
Angela Meadows, Suzanne Higgs, Sara E Burke, John F Dovidio, Michelle van Ryn, Sean M Phelan
Anti-fat bias in healthcare providers and medical students has serious implications for quality of care of higher-weight patients. Studies of interventions aimed at reducing anti-fat attitudes in medical students have generally been disappointing, with little enduring effect. It is possible that some students may be more receptive to prejudice-reducing influences than others, due to underlying differences in their personal characteristics. It is also possible that attitudes toward patients, specifically, may differ from anti-fat attitudes in general, and prejudice-reduction effectiveness on patient-specific attitudes has not yet been evaluated...
2017: Frontiers in Psychology
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