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https://www.readbyqxmd.com/read/29346838/first-in-human-study-to-assess-safety-pharmacokinetics-and-pharmacodynamics-of-bms-962212-a-direct-reversible-small-molecule-factor-xia-inhibitor-in-non-japanese-and-japanese-healthy-subjects
#1
Vidya Perera, Joseph M Luettgen, Zhaoqing Wang, Charles E Frost, Cynthia Yones, Cesare Russo, John Lee, Yue Zhao, Frank P LaCreta, Xuewen Ma, Robert M Knabb, Dietmar Seiffert, Mary DeSouza, Pierre Mugnier, Brenda Cirincione, Takayo Ueno, Robert J A Frost
AIMS: To assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of BMS-962212, a first-in-class Factor XIa inhibitor, in Japanese and non-Japanese healthy subjects. METHODS: This was a randomized, placebo-controlled, double-blind, sequential, ascending dose study of 2 hour (Part A) and 5 day (Part B) intravenous (IV) infusions of BMS-962212. Part A used 4 doses (1.5, 4, 10, and 25 mg h-1 ) assigned to BMS-962212 or placebo in a 3:1 ratio per dose. Part B used 4 doses (1, 3, 9, and 20 mg h-1 ) enrolling Japanese (n = 4 active, n = 1 placebo) and non-Japanese subjects (n = 4 active, n = 1 placebo) per dose...
January 18, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29346835/two-citrate-transporters-coordinately-regulate-citrate-secretion-from-rice-bean-root-tip-under-aluminum-stress
#2
Mei Ya Liu, He Qiang Lou, Wei Wei Chen, Miguel A Piñeros, Jia Meng Xu, Wei Fan, Leon V Kochian, Shao Jian Zheng, Jian Li Yang
Al-induced organic acid secretion from the root apex is an important Al resistance mechanism. However, it remains unclear how plants fine-tune root organic acid secretion which can contribute significantly to the loss of fixed carbon from the plant. Here, we demonstrate that Al-induced citrate secretion from the rice bean root apex is biphasic, consisting of an early phase with low secretion and a later phase of large citrate secretion. We isolated and characterized VuMATE2 as a possible second citrate transporter in rice bean functioning in tandem with VuMATE1, which we previously identified...
January 18, 2018: Plant, Cell & Environment
https://www.readbyqxmd.com/read/29346834/twelve-week-ravidasvir-plus-ritonavir-boosted-danoprevir-and-ribavirin-for-non-cirrhotic-hcv-genotype-1-patients-a-phase-2-study
#3
Jia-Horng Kao, Min-Lung Yu, Chi-Yi Chen, Cheng-Yuan Peng, Ming-Yao Chen, Huoling Tang, Qiaoqiao Chen, Jinzi J Wu
BACKGROUND AND AIM: The need for all-oral HCV treatments with higher response rates, improved tolerability and lower pill burden compared to interferon-inclusive regimen has led to the development of new direct-acting antiviral agents (DAAs). Ravidasvir (RDV) is a second-generation, pan-genotypic NS5A inhibitor with high barrier to resistance. The aim of this phase 2 study (EVERST study) was to assess the efficacy and safety of interferon-free, 12-week RDV plus ritonavir-boosted danoprevir (DNVr) and ribavirin (RBV) regimen for treatment-naïve Asian HCV genotype 1 (GT1) patients without cirrhosis...
January 18, 2018: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29346833/phase-1b-trial-of-ficlatuzumab-a-humanized-hepatocyte-growth-factor-inhibitory-monoclonal-antibody-in-combination-with-gefitinib-in-asian-patients-with-nsclc
#4
Eng-Huat Tan, Wan-Teck Lim, Myung-Ju Ahn, Quan-Sing Ng, Jin Seok Ahn, Daniel Shao-Weng Tan, Jong-Mu Sun, May Han, Francis C Payumo, Krista McKee, Wei Yin, Marc Credi, Shefali Agarwal, Jaroslaw Jac, Keunchil Park
Hepatocyte growth factor (HGF)/c-Met pathway dysregulation is a mechanism for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Ficlatuzumab (AV-299; SCH 900105), a humanized IgG1 κ HGF inhibitory monoclonal antibody, prevents HGF/c-Met pathway ligand-mediated activation. This phase 1b study assessed the safety/tolerability, pharmacokinetics/pharmacodynamics, and antitumor activity of ficlatuzumab plus gefitinib in Asian patients with previously treated advanced non-small cell lung cancer (NSCLC)...
January 18, 2018: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29346828/dynamic-posterior-stabilization-versus-posterior-lumbar-intervertebral-fusion-a-matched-cohort-study-based-on-the-spine-tango-registry
#5
Kathrin S Bieri, Kelly Goodwin, Emin Aghayev, Hans-Joachim Riesner, Ralph Greiner-Perth
PURPOSE:  The primary aim of dynamic stabilization is to stabilize the spine and preserve function without overstressing adjacent segments, which is a potential risk of fusion surgery. However, direct comparative analyses of the two approaches are still limited, and little is known about the association of patient-reported outcomes with these treatment options. OBJECTIVE:  To compare the clinical outcomes of dynamic posterior stabilization using the DSS Stabilization System (Paradigm Spine, LLC, New York, New York, United States) versus posterior lumbar intervertebral fusion (PLIF) based on data from a spine registry...
January 18, 2018: Journal of Neurological Surgery. Part A, Central European Neurosurgery
https://www.readbyqxmd.com/read/29346805/mesenteric-vessel-patency-following-hifu-therapy-in-patients-with-locally-invasive-pancreatic-cancer
#6
Holger M Strunk, Caroline Lützow, Jana Henseler, Martin Mücke, Maximilian Rauch, Christian Marx, Hans H Schild, Milka Marinova
PURPOSE:  To evaluate the effects of HIFU therapy on visceral vessel patency in patients with inoperable locally invasive pancreatic cancer. MATERIALS AND METHODS:  50 pancreatic cancer patients (26 men, 24 women) aged 41 - 82 years (65.0 ± 10.2) underwent ultrasonography (US) and computed tomography (CT) examinations before and within one day after HIFU treatment, as well as at follow-up at six weeks, three months and six months. Evaluation and grading were performed by two experienced independent radiologists according to a classification scheme based on vessel involvement, vessel diameter, patency, and defects in flow...
January 18, 2018: Ultraschall in der Medizin
https://www.readbyqxmd.com/read/29346796/background-factors-and-subjective-voice-symptoms-in-patients-with-acquired-vocal-fold-scarring-and-sulcus-vocalis
#7
Emma Malmström, Stellan Hertegård
OBJECTIVE: Vocal fold scarring (VFS) and sulcus vocalis (SV) often result in severe and chronic voice disorders. This study compares subjective voice complaints as rated with the Voice Handicap Index and etiological factors for patients with VFS and SV. PATIENTS AND METHODS: Data were collected from the medical records at the Department of Otorhinolaryngology, Karolinska University Hospital, for 27 VFS patients and 27 SV patients. Descriptive background factors were compared between the groups and data were compared from the Swedish Voice Handicap Index (Sw-VHI) questionnaires...
January 18, 2018: Folia Phoniatrica et Logopaedica
https://www.readbyqxmd.com/read/29346793/epicardial-fat-thickness-in-non-obese-neurologically-impaired-children-association-with-unfavorable-cardiometabolic-risk-profile
#8
Valeria Calcaterra, Hellas Cena, Pietro Mariano Casali, Gianluca Iacobellis, Riccardo Albertini, Mara De Amici, Annalisa de Silvestri, Calogero Comparato, Gloria Pelizzo
BACKGROUND: Cardiovascular risk is reported in disabled children and epicardial fat (EF) is considered an independent predictor of cardiovascular disease (CVD). No data on the EF thickness (EFT) evaluation in disabled children have been published. OBJECTIVE: We investigated EFT in neurologically impaired (NI) children; its relationship with their metabolic profile was also considered. METHODS: Clinical data, body composition estimation, biochemical profile, and ultrasound-measured EFT were performed in 32 disabled patients (12...
January 18, 2018: Annals of Nutrition & Metabolism
https://www.readbyqxmd.com/read/29346789/mentalization-and-self-efficacy-as-mediators-between-psychological-symptom-severity-and-disabilities-in-activities-and-participation-in-psychotherapy-patients
#9
Thomas Probst, Maria Dehoust, Anna Levke Brütt, Holger Schulz, Christoph Pieh, Sylke Andreas
BACKGROUND: Psychotherapy patients can be more or less disabled by their psychological symptoms. The present study investigated whether mentalization and self-efficacy contribute to the association between psychological symptom severity and disabilities in activities and participation. METHODS: The data of 216 psychotherapy inpatients were examined in a cross-sectional design. Bootstrapping-enhanced mediation analyses were performed to investigate whether self-efficacy and mentalization are mediators between psychological symptom severity and disabilities in activities and participation...
January 19, 2018: Psychopathology
https://www.readbyqxmd.com/read/29346788/vitamin-d-classic-and-novel-actions
#10
Ángel Gil, Julio Plaza-Diaz, María Dolores Mesa
BACKGROUND: Classically, vitamin D has been implicated in bone health by promoting calcium absorption in the gut and maintenance of serum calcium and phosphate concentrations, as well as by its action on bone growth and reorganization through the action of osteoblasts and osteoclasts cells. However, in the last 2 decades, novel actions of vitamin D have been discovered. The present report summarizes both classic and novel actions of vitamin D. SUMMARY: 1,25(OH)2 vitamin D, the active metabolite of vitamin D, also known as calcitriol, regulates not only calcium and phosphate homeostasis but also cell proliferation and differentiation, and has a key a role to play in the responses of the immune and nervous systems...
January 18, 2018: Annals of Nutrition & Metabolism
https://www.readbyqxmd.com/read/29346778/diverse-brain-myeloid-expression-profiles-reveal-distinct-microglial-activation-states-and-aspects-of-alzheimer-s-disease-not-evident-in-mouse-models
#11
Brad A Friedman, Karpagam Srinivasan, Gai Ayalon, William J Meilandt, Han Lin, Melanie A Huntley, Yi Cao, Seung-Hye Lee, Patrick C G Haddick, Hai Ngu, Zora Modrusan, Jessica L Larson, Joshua S Kaminker, Marcel P van der Brug, David V Hansen
Microglia, the CNS-resident immune cells, play important roles in disease, but the spectrum of their possible activation states is not well understood. We derived co-regulated gene modules from transcriptional profiles of CNS myeloid cells of diverse mouse models, including new tauopathy model datasets. Using these modules to interpret single-cell data from an Alzheimer's disease (AD) model, we identified microglial subsets-distinct from previously reported "disease-associated microglia"-expressing interferon-related or proliferation modules...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346772/peroxisome-proliferator-activated-receptor-gamma-controls-mature-brown-adipocyte-inducibility-through-glycerol-kinase
#12
David Lasar, Matthias Rosenwald, Elke Kiehlmann, Miroslav Balaz, Bettina Tall, Lennart Opitz, Martin E Lidell, Nicola Zamboni, Petra Krznar, Wenfei Sun, Lukas Varga, Patrik Stefanicka, Jozef Ukropec, Pirjo Nuutila, Kirsi Virtanen, Ez-Zoubir Amri, Sven Enerbäck, Walter Wahli, Christian Wolfrum
Peroxisome proliferator-activated receptors (PPARs) have been suggested as the master regulators of adipose tissue formation. However, their role in regulating brown fat functionality has not been resolved. To address this question, we generated mice with inducible brown fat-specific deletions of PPARα, β/δ, and γ, respectively. We found that both PPARα and β/δδ are dispensable for brown fat function. In contrast, we could show that ablation of PPARγ in vitro and in vivo led to a reduced thermogenic capacity accompanied by a loss of inducibility by β-adrenergic signaling, as well as a shift from oxidative fatty acid metabolism to glucose utilization...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346769/switching-on-depression-and-potentiation-in-the-cerebellum
#13
Andrew R Gallimore, Taegon Kim, Keiko Tanaka-Yamamoto, Erik De Schutter
Long-term depression (LTD) and long-term potentiation (LTP) in the cerebellum are important for motor learning. However, the signaling mechanisms controlling whether LTD or LTP is induced in response to synaptic stimulation remain obscure. Using a unified model of LTD and LTP at the cerebellar parallel fiber-Purkinje cell (PF-PC) synapse, we delineate the coordinated pre- and postsynaptic signaling that determines the direction of plasticity. We show that LTP is the default response to PF stimulation above a well-defined frequency threshold...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346765/characterization-of-endothelial-cells-associated-with-hematopoietic-niche-formation-in-humans-identifies-il-33-as-an-anabolic-factor
#14
Keane Jared Guillaume Kenswil, Adrian Christopher Jaramillo, Zhen Ping, Si Chen, Remco Michiel Hoogenboezem, Maria Athina Mylona, Maria Niken Adisty, Eric Moniqué Johannes Bindels, Pieter Koen Bos, Hans Stoop, King Hong Lam, Bram van Eerden, Tom Cupedo, Marc Hermanus Gerardus Petrus Raaijmakers
Bone marrow formation requires an orchestrated interplay between osteogenesis, angiogenesis, and hematopoiesis that is thought to be mediated by endothelial cells. The nature of the endothelial cells and the molecular mechanisms underlying these events remain unclear in humans. Here, we identify a subset of endoglin-expressing endothelial cells enriched in human bone marrow during fetal ontogeny and upon regeneration after chemotherapeutic injury. Comprehensive transcriptional characterization by massive parallel RNA sequencing of these cells reveals a phenotypic and molecular similarity to murine type H endothelium and activation of angiocrine factors implicated in hematopoiesis, osteogenesis, and angiogenesis...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346744/2017-national-standards-for-diabetes-self-management-education-and-support
#15
Joni Beck, Deborah A Greenwood, Lori Blanton, Sandra T Bollinger, Marcene K Butcher, Jo Ellen Condon, Marjorie Cypress, Priscilla Faulkner, Amy Hess Fischl, Theresa Francis, Leslie E Kolb, Jodi M Lavin-Tompkins, Janice MacLeod, Melinda Maryniuk, Carolé Mensing, Eric A Orzeck, David D Pope, Jodi L Pulizzi, Ardis A Reed, Andrew S Rhinehart, Linda Siminerio, Jing Wang
Purpose The purpose of this study is to review the literature for Diabetes Self-Management Education and Support (DSMES) to ensure the National Standards for DSMES (Standards) align with current evidence-based practices and utilization trends. Methods The 10 Standards were divided among 20 interdisciplinary workgroup members. Members searched the current research for diabetes education and support, behavioral health, clinical, health care environment, technical, reimbursement, and business practice for the strongest evidence that guided the Standards revision...
February 2018: Diabetes Educator
https://www.readbyqxmd.com/read/29346742/management-of-children-with-diabetes-in-the-school-setting
#16
(no author information available yet)
Diabetes educators are well positioned to help optimize care of the student with diabetes within the school setting.
February 2018: Diabetes Educator
https://www.readbyqxmd.com/read/29346735/mechanisms-of-modulation-of-calcium-phosphate-pathological-mineralization-by-mobile-and-immobile-small-molecule-inhibitors
#17
Meng Li, Jing Zhang, Lijun Wang, Baoshan Wang, Christine V Putnis
Potential pathways for inhibiting crystal growth are either via disrupting local microenvironments surrounding crystal-solution interfaces or physically blocking solute molecule attachment. However, the actual mode of inhibition may be more complicated due to the characteristic time scale for the inhibitor adsorption and relaxation to a well-bound state at crystal surfaces. Here we demonstrate the role of citrate (CA) and hydroxycitrate (HCA) in brushite (DCPD, CaHPO4·2H2O) crystallization over a broad range of both inhibitor concentrations and supersaturations by in situ atomic force microscopy (AFM)...
January 18, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29346734/fluctuation-effects-on-the-brush-structure-of-mixed-brush-nanoparticles-in-solution
#18
Jason P Koski, Amalie L Frischknecht
A potentially attractive way to control nanoparticle assembly is to graft one or more polymers on the nanoparticle, to control the nanoparticle-nanoparticle interactions. When two immiscible polymers are grafted on the nanoparticle, they can microphase separate to form domains at the nanoparticle surface. Here we computationally investigate the phase behavior of such binary mixed brush nanoparticles in solution, across a large and experimentally relevant parameter space. Specifically, we calculate the mean-field phase diagram, assuming uniform grafting of the two polymers, as a function of the nanoparticle size relative to the length of the grafted chains, the grafting density, the enthalpic repulsion between the grafted chains, and the solvent quality...
January 18, 2018: ACS Nano
https://www.readbyqxmd.com/read/29346732/microscopic-theory-of-coupled-slow-activated-dynamics-in-glass-forming-binary-mixtures
#19
Rui Zhang, Kenneth S Schweizer
The Elastically Collective Nonlinear Langevin Equation theory for one-component viscous liquids and suspensions is generalized to treat coupled slow activated relaxation and diffusion in glass-forming binary sphere mixtures of any composition, size ratio and inter-particle interactions. A trajectory-level dynamical coupling parameter concept is introduced to construct two coupled dynamic free energy functions for the smaller penetrant and larger matrix particle. A two-step dynamical picture is proposed where the first step process involves matrix-facilitated penetrant hopping quantified in a self-consistent manner based on a temporal coincidence condition...
January 18, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29346730/2d-spectroscopy-is-being-used-to-address-core-scientific-questions-in-biology-and-materials-science
#20
Megan Petti, Justin P Lomont, Michał Maj, Martin T Zanni
Two-dimensional spectroscopy is a powerful tool for extracting structural and dynamic information from a wide range of chemical systems. We provide a brief overview of the ways in which two-dimensional visible and infrared spectroscopies are being applied to elucidate fundamental details of important processes in biological and materials science. The topics covered include amyloid proteins, photo-synthetic complexes, ion channels, photovoltaics, batteries, as well as a variety of promising new methods in two-dimensional spectroscopy...
January 18, 2018: Journal of Physical Chemistry. B
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