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https://www.readbyqxmd.com/read/28431186/unfractionated-heparin-versus-low-molecular-weight-heparins-for-avoiding-heparin-induced-thrombocytopenia-in-postoperative-patients
#1
REVIEW
Daniela R Junqueira, Liliane M Zorzela, Edson Perini
BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction presenting as a prothrombotic disorder related to antibody-mediated platelet activation. It is a paradoxical immune reaction resulting in thrombin generation in vivo, which leads to a hypercoagulable state and the potential to initiate venous or arterial thrombosis. A number of factors are thought to influence the incidence of HIT including the type and preparation of heparin (unfractionated heparin (UFH) or low molecular weight heparin (LMWH)) and the heparin-exposed patient population, with the postoperative patient population at higher risk...
April 21, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28430758/the-refractive-error-of-professional-baseball-players
#2
Daniel M Laby, David G Kirschen
PURPOSE: High levels of visual acuity are required to hit a baseball effectively. Research has shown that any decrease in vision is likely caused by low-order optical aberrations. This study is designed to validate the SVOne autorefractor, and describe the amount and type, of low-order optical aberrations present in a large cohort of professional baseball players. METHODS: A retrospective chart review on the 608 Major League Baseball players evaluated during the 2016 Spring Training Season was performed...
May 2017: Optometry and Vision Science: Official Publication of the American Academy of Optometry
https://www.readbyqxmd.com/read/28430437/discovery-of-an-hcv-ns5b-replicase-palm-site-allosteric-inhibitor-bms-929075-advanced-to-phase-1-clinical-studies
#3
Kap-Sun Yeung, Brett R Beno, Kyle Parcella, John A Bender, Katherine A Grant-Young, Andrew Nickel, Prashantha Gunaga, Prakash Anjanappa, Rajesh Onkardas Bora, Kumaravel Selvakumar, Karen Rigat, Ying-Kai Wang, Mengping Liu, Julie A Lemm, Kathy Mosure, Steven Sheriff, Changhong Wan, Mark Witmer, Kevin Kish, Umesh M Hanumegowda, Xiaoliang Zhuo, Yue-Zhong Shu, Dawn Parker, Roy Haskell, Alicia Ng, Qi Gao, Elizabeth Colston, Joseph Raybon, Dennis M Grasela, Kenneth S Santone, Min Gao, Nicholas A Meanwell, Michael W Sinz, Matthew G Soars, Jay O Knipe, Susan B Roberts, John F Kadow
The hepatitis C virus NS5B replicase is a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection. Inspired by the overlay of bound structures of three structurally distinct NS5B palm site allosteric inhibitors, the high throughput screening hit anthranilic acid 4, the known benzofuran analog 5 and the benzothiadiazine derivative 6, an optimization process utilizing the simple benzofuran template 7 as a starting point for a fragment growing approach was pursued...
April 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28430158/identification-of-tight-binding-plasmepsin-ii-and-falcipain-2-inhibitors-in-aqueous-extracts-of-marine-invertebrates-by-the-combination-of-enzymatic-and-interaction-based-assays
#4
Emir Salas-Sarduy, Yasel Guerra, Giovanni Covaleda Cortés, Francesc Xavier Avilés, María A Chávez Planes
Natural products from marine origin constitute a very promising and underexplored source of interesting compounds for modern biotechnological and pharmaceutical industries. However, their evaluation is quite challenging and requires specifically designed assays to reliably identify the compounds of interest in a highly heterogeneous and interfering context. In the present study, we describe a general strategy for the confident identification of tight-binding protease inhibitors in the aqueous extracts of 62 Cuban marine invertebrates, using Plasmodium falciparum hemoglobinases Plasmepsin II and Falcipain 2 as model enzymes...
April 21, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28429867/health-related-quality-of-life-questionnaires-in-individuals-with-haemophilia-a-systematic-review-of-their-measurement-properties
#5
REVIEW
P F Limperg, C B Terwee, N L Young, V E Price, S C Gouw, M Peters, M A Grootenhuis, V Blanchette, L Haverman
BACKGROUND: The evaluation of health related quality of life (HRQOL) is essential for a full assessment of the influence of an illness on patients' lives. The aim of this paper is to critically appraise and compare the measurement properties of HRQOL questionnaires studied in haemophilia. METHODS: Bibliographic databases (Embase, Medline, Cinahl and PsycInfo) were searched for articles evaluating measurement properties of HRQOL questionnaires in haemophilia. Articles were excluded that did not report HRQOL measurement properties, or when <50% of the study population had haemophilia...
April 21, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28429752/lncrna-hit-promotes-cell-proliferation-of-non-small-cell-lung-cancer-by-association-with-e2f1
#6
L Yu, F Fang, S Lu, X Li, Y Yang, Z Wang
Lung cancer is the leading cause of cancer-related death around the world. Long noncoding RNA (lncRNA) has pivotal roles in cancer occurrence and development. However, only a few lncRNAs have been functionally characterized. In the present study, we investigated the effects of lncRNA-HIT (HOXA transcript induced by TGFβ) expression on non-small cell lung cancer (NSCLC) cell phenotype with the gain-of-function and loss-of-function assays. We found that ectopic expression or knockdown of lncRNA-HIT markedly increased or decreased NSCLC cell proliferation, respectively...
April 21, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28428256/regulation-of-lung-endothelial-permeability-and-inflammatory-responses-by-prostaglandin-a2-role-of-ep4-receptor
#7
Tomomi Ohmura, Yufeng Tian, Nicolene Sarich, Yunbo Ke, Angelo Meliton, Alok S Shah, Katrin Andreasson, Konstantin G Birukov, Anna A Birukova
A role of prostaglandin A2 (PGA2) in modulation of vascular endothelial function remains unknown. We investigated effects of PGA2 on pulmonary endothelial cell (EC) permeability and inflammatory activation and identified a receptor mediating these effects. PGA2 enhanced the EC barrier and protected against barrier dysfunction caused by vasoactive peptide thrombin and proinflammatory bacterial wall lipopolysacharide (LPS). Receptor screening using pharmacologic and molecular inhibitory approaches identified EP4 as a novel PGA2 receptor...
April 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28427966/intravenous-immunoglobulin-for-treatment-of-severe-refractory-heparin-induced-thrombocytopenia
#8
Anand Padmanabhan, Curtis G Jones, Shannon M Pechauer, Brian R Curtis, Daniel W Bougie, Mehraboon S Irani, Barbara J Bryant, Jack B Alperin, Thomas G Deloughery, Kevin P Mulvey, Binod Dhakal, Renren Wen, Demin Wang, Richard H Aster
BACKGROUND: HIT complicated by severe thrombocytopenia and thrombosis can pose significant treatment challenges. Use of alternative anticoagulants in this setting may increase bleeding risks, especially in patients who have a protracted disease course. Additional therapies are lacking in this severely affected patient population. METHODS: We describe three HIT patients who had severe thromboembolism and prolonged thrombocytopenia refractory to standard treatment but achieved an immediate and sustained response to intravenous immunoglobulin G (IVIg) therapy...
April 17, 2017: Chest
https://www.readbyqxmd.com/read/28427443/benserazide-a-dopadecarboxylase-inhibitor-suppresses-tumor-growth-by-targeting-hexokinase-2
#9
Wei Li, Mengzhu Zheng, Shuangping Wu, Suyu Gao, Mei Yang, Zhimei Li, Qiuxia Min, Weiguang Sun, Lixia Chen, Guangya Xiang, Hua Li
BACKGROUND: Hexokinase (HK) is the rate-limiting enzyme in the first reaction of glycolysis. And Hexokinase 2 (HK2) is most closely related to malignant tumor which expresses at higher level compared with normal cells. HK2 plays a pivotal role in tumor initiation and maintenance, which provides a new target for cancer therapy. METHODS: Structure-based virtual ligand screening was used in hit identification from ZINC Drug Database. Microscale thermophoresis assay was performed to evaluate the binding affinity...
April 20, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28427007/novel-and-revisited-approaches-in-antituberculosis-drug-discovery
#10
REVIEW
Jennifer Herrmann, Jan Rybniker, Rolf Müller
The increasing prevalence of multidrug-resistant Mycobacterium tuberculosis (Mtb) necessitates the discovery and development of novel drugs against tuberculosis. In this review, we focus on two recent approaches that led to the discovery of promising antitubercular compound classes: (I) Hits derived from large compound library screens are increasingly difficult to translate into clinical application; this in turn fostered the development of innovative screening methods. (II) An alternative strategy towards high-quality hits and leads is to evaluate chemically diverse scaffolds which can be found among natural products...
April 17, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28426940/prospective-assessment-of-virtual-screening-heuristics-derived-using-a-novel-fusion-score
#11
Dante A Pertusi, Gregory O'Donnell, Michelle F Homsher, Kelli Solly, Amita Patel, Shannon L Stahler, Daniel Riley, Michael F Finley, Eleftheria N Finger, Gregory C Adam, Juncai Meng, David J Bell, Paul D Zuck, Edward M Hudak, Michael J Weber, Jennifer E Nothstein, Louis Locco, Carissa Quinn, Adam Amoss, Brian Squadroni, Michelle Hartnett, Mee Ra Heo, Tara White, S Alex May, Evelyn Boots, Kenneth Roberts, Patrick Cocchiarella, Alex Wolicki, Anthony Kreamer, Peter S Kutchukian, Anne Mai Wassermann, Victor N Uebele, Meir Glick, Andrew Rusinko, J Christopher Culberson
High-throughput screening (HTS) is a widespread method in early drug discovery for identifying promising chemical matter that modulates a target or phenotype of interest. Because HTS campaigns involve screening millions of compounds, it is often desirable to initiate screening with a subset of the full collection. Subsequently, virtual screening methods prioritize likely active compounds in the remaining collection in an iterative process. With this approach, orthogonal virtual screening methods are often applied, necessitating the prioritization of hits from different approaches...
April 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28426938/high-throughput-screening-to-identify-inhibitors-of-dead-box-helicase-ddx41
#12
Mariko Yoneyama-Hirozane, Mitsuyo Kondo, Shin-Ichi Matsumoto, Akiko Morikawa-Oki, Daisuke Morishita, Atsushi Nakanishi, Tomohiro Kawamoto, Masaharu Nakayama
The human DEAD (Asp-Glu-Ala-Asp) box protein DDX41, a member of the DEXDc helicase family, has nucleic acid-dependent ATPase and RNA and DNA translocase and unwinding activities. DDX41 is affected by somatic mutations in sporadic cases of myeloid neoplasms as well as in a biallelic fashion in 50% of patients with germline DDX41 mutations. The R525H mutation in DDX41 is thought to play important roles in the development of hereditary myelodysplastic syndrome and acute myelocytic leukemia. In this study, human DDX41 and its R525H mutant (R525H) were expressed in Escherichia coli and purified...
April 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28426709/pdgfrb-is-a-direct-regulatory-target-of-tgf%C3%AE-signaling-in-atrioventricular-cushion-mesenchymal-cells
#13
Yin Peng, Shun Yan, Dongquan Chen, Xiangqin Cui, Kai Jiao
Cushion formation is the initial step for the development of valvuloseptal structures in mammalian hearts. TGFβ signaling plays critical roles in multiple steps of cushion morphogenesis. We used a newly developed conditional immortal atrioventricular cushion mesenchymal cell line, tsA58-AVM, to identify the TGFβ regulatory target genes through microarray analysis. Expression of ~1350 genes was significantly altered by TGFβ1 treatment. Subsequent bioinformatic analysis of TGFβ activated genes revealed that PDGF-BB signaling is the top hit as the potential upstream regulator...
2017: PloS One
https://www.readbyqxmd.com/read/28426560/universal-screening-for-intimate-partner-and-sexual-violence-in-trauma-patients-an-east-multicenter-trial
#14
Tanya L Zakrison, Xiomara Ruiz, Rondi Gelbard, John Cline, David Turay, Xian Luo-Owen, Nicholas Namias, Marie Crandall, Jessica George, Brian H Williams
BACKGROUND: A single center trial recently demonstrated a prevalence of 14% of intimate partner and sexual violence (IPSV) amongst both male and female trauma patients, regardless of mechanism of injury. We aimed to determine if this phenomenon was similar to rates in other trauma centers by assessing the feasibility of universal screening, and determining the prevalence and association of IPSV with other trauma-associated comorbidities. METHODS: We designed an EAST- supported multicenter, prospective observational cohort study involving four Level I trauma centers throughout the United States...
April 20, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28426320/transient-exposure-to-androgens-induces-a-remarkable-self-sustained-quiescent-state-in-dispersed-prostate-cancer-cells
#15
Anh Thu Bui, Meng-Er Huang, Maryline Havard, Fanny Laurent-Tchenio, François Dautry, Thierry Tchenio
Cellular quiescence is a reversible cell growth arrest that is often assumed to require a persistence of non-permissive external growth conditions for its maintenance. In this work, we showed that androgen could induce a quiescent state that is self-sustained in a cell-autonomous manner through a "hit and run" mechanism in androgen receptor-expressing prostate cancer cells. This phenomenon required the set-up of a sustained redox imbalance and TGFβ/BMP signaling that were dependent on culturing cells at low density...
April 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28425495/the-biglen-gpr171-peptide-receptor-system-within-the-basolateral-amygdala-regulates-anxiety-like-behavior-and-contextual-fear-conditioning
#16
Erin N Bobeck, Ivone Gomes, Darlene Pena, Kirstie A Cummings, Roger L Clem, Mihaly Mezei, Lakshmi A Devi
Studies show that neuropeptide-receptor systems in the basolateral amygdala (BLA) play an important role in the pathology of anxiety and other mood disorders. Since GPR171, a recently deorphanized receptor for the abundant neuropeptide BigLEN, is expressed in the BLA, we investigated its role in fear and anxiety-like behaviors. To carry out these studies we identified small molecule ligands using a homology model of GPR171 to virtually screen a library of compounds. One of the hits, MS0021570_1, was identified as a GPR171 antagonist based on its ability to block (i) BigLEN-mediated activation of GPR171 in heterologous cells, (ii) BigLEN-mediated hyperpolarization of BLA pyramidal neurons, and (iii) feeding induced by DREADD-mediated activation of BigLEN containing AgRP neurons in the arcuate nucleus...
April 20, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28424897/first-step-in-telehealth-assessment-a-randomized-controlled-trial-to-investigate-the-effectiveness-of-an-electronic-case-history-form-for-dysphagia
#17
Cagla Kantarcigil, Georgia A Malandraki
The need for developing effective telehealth tools for dysphagia management is high not only for people who live in rural areas, but also for individuals with mobility/access limitations. We aimed to develop an electronic case History Tool/form (thereafter, e-HiT) for dysphagia, and compare its effectiveness with its paper-based version (PBV) on completion time, completeness, independence, and patient perceptions/satisfaction. Secondarily, we examined associations between the aforementioned variables and predictor variables, such as age, cognition, and computer/internet use...
April 19, 2017: Dysphagia
https://www.readbyqxmd.com/read/28424078/interleukin-6-displays-lung-anti-inflammatory-properties-and-exerts-protective-hemodynamic-effects-in-a-double-hit-murine-acute-lung-injury
#18
Guillaume Voiriot, Keyvan Razazi, Valérie Amsellem, Jeanne Tran Van Nhieu, Shariq Abid, Serge Adnot, Armand Mekontso Dessap, Bernard Maitre
BACKGROUND: Interleukin 6 (IL-6) is a predictive factor of poor prognosis in patients with acute respiratory distress syndrome (ARDS). However, its acute pulmonary hemodynamic effects and role in lung injury have not been investigated in a clinically relevant murine model of ARDS. METHODS: We used adult C57Bl6 wild-type (WT) and IL-6 knock-out (IL-6KO) mice. The animals received intravenous recombinant human IL-6 (rHuIL-6) or vehicle followed by intratracheal lipopolysaccharide (LPS) or saline before undergoing low tidal volume mechanical ventilation (MV) for 5 h...
April 19, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28424031/yellow-fever-from-angola-and-congo-a-storm-gathers
#19
Qanta A Ahmed, Ziad A Memish
In common with Zika, Chikungunya and Dengue, Yellow Fever (YF) is an arthropod-borne flavivirus. It is transmitted between humans and from monkeys by mosquitoes of the Aedes aegypti (its principal vector), haemogogus and albopictus varieties. Three cycles of transmission may occur: urban; sylvatic; and intermediate. Recently, sub-Saharan Africa has seen the resurgence of this neglected disease. The current YF outbreak in Angola began in December 2015 in the capital Luanda and by October 2016 there had been > 4300 suspected cases, with 376 deaths (case fatality rate = 8...
April 2017: Tropical Doctor
https://www.readbyqxmd.com/read/28423817/persona-development-and-educational-needs-to-support-informal-caregivers
#20
Zeina Al Awar, Craig Kuziemsky
Informal caregivers are playing an increasing role in community based care delivery. Research is needed that looks at the educational needs of informal caregivers as a precursor to HIT design to support community care delivery. A challenge is informal caregivers have very diverse educational needs. Personas are an approach to describe user characteristics as part of systems design and this approach could be used to understand and categorize the various educational needs of informal caregivers. This paper addresses this research need and provides a method for persona development and the identification of educational needs for informal caregivers...
2017: Studies in Health Technology and Informatics
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