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https://www.readbyqxmd.com/read/28732272/screening-of-the-open-scaffolds-collection-from-compounds-australia-identifies-a-new-chemical-entity-with-anthelmintic-activities-against-different-developmental-stages-of-the-barber-s-pole-worm-and-other-parasitic-nematodes
#1
Sarah Preston, Yaqing Jiao, Jonathan B Baell, Jennifer Keiser, Simon Crawford, Anson V Koehler, Tao Wang, Moana M Simpson, Ray M Kaplan, Karla J Cowley, Kaylene J Simpson, Andreas Hofmann, Abdul Jabbar, Robin B Gasser
The discovery and development of novel anthelmintic classes is essential to sustain the control of socioeconomically important parasitic worms of humans and animals. With the aim of offering novel, lead-like scaffolds for drug discovery, Compounds Australia released the 'Open Scaffolds' collection containing 33,999 compounds, with extensive information available on the physicochemical properties of these chemicals. In the present study, we screened 14,464 prioritised compounds from the 'Open Scaffolds' collection against the exsheathed third-stage larvae (xL3s) of Haemonchus contortus using recently developed whole-organism screening assays...
May 28, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28732151/patients-attitudes-and-experiences-of-disease-modifying-anti-rheumatic-drugs-in-rheumatoid-arthritis-and-spondyloarthritis-a-qualitative-synthesis
#2
Ayano Kelly, Kathleen Tymms, David J Tunnicliffe, Daniel Sumpton, Chandima Perera, Kieran Fallon, Jonathan C Craig, Walter Abhayaratna, Allison Tong
OBJECTIVES: Non-adherence to disease-modifying anti-rheumatic drugs (DMARDS) in rheumatoid arthritis (RA) and spondyloarthritis (SpA) results in increased disease activity and symptoms and poorer quality of life. We aimed to describe patients' attitudes and experiences of DMARDs in RA and SpA to inform strategies to improve medication adherence. METHODS: Databases (MEDLINE, Embase, PsycINFO, CINAHL) were searched to January 2016. Thematic synthesis was used to analyze the findings...
July 21, 2017: Arthritis Care & Research
https://www.readbyqxmd.com/read/28732138/involving-citizens-in-priority-setting-for-public-health-research-implementation-in-infection-research
#3
Timothy M Rawson, Enrique Castro-Sánchez, Esmita Charani, Fran Husson, Luke S P Moore, Alison H Holmes, Raheelah Ahmad
BACKGROUND: Public sources fund the majority of UK infection research, but citizens currently have no formal role in resource allocation. To explore the feasibility and willingness of citizens to engage in strategic decision making, we developed and tested a practical tool to capture public priorities for research. METHOD: A scenario including six infection themes for funding was developed to assess citizen priorities for research funding. This was tested over two days at a university public festival...
July 21, 2017: Health Expectations: An International Journal of Public Participation in Health Care and Health Policy
https://www.readbyqxmd.com/read/28732067/thromboembolic-adverse-event-study-of-combined-estrogen-progestin-preparations-using-japanese-adverse-drug-event-report-database
#4
Shiori Hasegawa, Toshinobu Matsui, Yuuki Hane, Junko Abe, Haruna Hatahira, Yumi Motooka, Sayaka Sasaoka, Akiho Fukuda, Misa Naganuma, Kouseki Hirade, Yukiko Takahashi, Yasutomi Kinosada, Mitsuhiro Nakamura
Combined estrogen-progestin preparations (CEPs) are associated with thromboembolic (TE) side effects. The aim of this study was to evaluate the incidence of TE using the Japanese Adverse Drug Event Report (JADER) database. Adverse events recorded from April 2004 to November 2014 in the JADER database were obtained from the Pharmaceuticals and Medical Devices Agency (PMDA) website (www.pmda.go.jp). We calculated the reporting odds ratios (RORs) of suspected CEPs, analyzed the time-to-onset profile, and assessed the hazard type using Weibull shape parameter (WSP)...
2017: PloS One
https://www.readbyqxmd.com/read/28731889/stent-thrombosis-with-bioabsorbable-polymer-drug-eluting-stents-insights-from-the-food-and-drug-administration-database
#5
Abdur R Khan, Avnish Tripathi, Talha A Farid, Bilal Abaid, Deepak L Bhatt, Jon R Resar, Michael P Flaherty
BACKGROUND: SYNERGY, a bioabsorbable polymer-based, everolimus-eluting stent (BP-DES), recently received regulatory approval in the USA for use in percutaneous coronary interventions. Yet, information on the safety of BP-DES in routine clinical practice is limited. Our aim was to compare the safety of the recently approved BP-DES with current durable polymer drug-eluting stents (DP-DES) by analyzing adverse events, namely, stent thrombosis (ST), reported to the Manufacturer and User Facility Device Experience (MAUDE) database...
July 20, 2017: Coronary Artery Disease
https://www.readbyqxmd.com/read/28731335/a-simple-representation-of-three-dimensional-molecular-structure
#6
Seth D Axen, Xi-Ping Huang, Elena L Cáceres, Leo Gendelev, Bryan L Roth, Michael J Keiser
Statistical and machine learning approaches predict drug-to-target relationships from 2D small-molecule topology patterns. One might expect 3D information to improve these calculations. Here we apply the logic of the Extended Connectivity FingerPrint (ECFP) to develop a rapid, alignment-invariant 3D representation of molecular conformers, the Extended Three-Dimensional FingerPrint (E3FP). By integrating E3FP with the Similarity Ensemble Approach (SEA), we achieve higher precision-recall performance relative to SEA with ECFP on ChEMBL20, and equivalent receiver operating characteristic performance...
July 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28731207/polyclonal-and-monoclonal-antibodies-for-treating-acute-rejection-episodes-in-kidney-transplant-recipients
#7
REVIEW
Angela C Webster, Sunny Wu, Krishna Tallapragada, Min Young Park, Jeremy R Chapman, Sue J Carr
BACKGROUND: Registry data shows that the incidence of acute rejection has been steadily falling. Approximately 10% to 35% of kidney recipients will undergo treatment for at least one episode of acute rejection within the first post-transplant year. Treatment options include pulsed steroid therapy, the use of an antibody preparation, the alteration of background immunosuppression, or combinations of these options. Over recent years, new treatment strategies have evolved, and in many parts of the world there has been an increase in use of tacrolimus and mycophenolate and a reduction in the use of cyclosporin and azathioprine use as baseline immunosuppression to prevent acute rejection...
July 20, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28731149/the-role-of-t-helper-17-cells-in-the-pathogenesis-of-hepatitis-b-virus-related-liver-cirrhosis-review
#8
Suxia Bao, Jianming Zheng, Guangfeng Shi
In chronic hepatitis B virus (HBV)-infected patients, T helper 17 (Th17) cells are significantly elevated. Th17 cells initiate immune‑mediated pathogenesis and have a critical role in the process of HBV‑related liver cirrhosis (HBV‑LC). The mechanisms underlying this process are attributed to Th17‑secreted cytokines, which include interleukin (IL)‑17, IL‑21 and IL‑22; however, a systemic analysis regarding these mechanisms has yet to be conducted. Therefore, the present study aimed to investigate the role of Th17 cells in the pathogenesis of HBV‑LC...
July 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28730936/an-industry-update-what-is-the-latest-news-in-therapeutic-delivery
#9
Iain Simpson
This Industry Update covers the period from 1 through 30 April 2017, and is based on information sourced from company press releases, scientific literature, patents and various news websites. Biogen expanded its portfolio of developmental drugs targeting neurological diseases by licensing a drug from Bristol-Myers Squibb which is currently under investigation for the treatment of progressive supranuclear palsy. Takeda announced a deal with NuBiyota focused on developing treatments for gastrointestinal disorders, based on the manipulation of microbes living in the gut...
July 2017: Therapeutic Delivery
https://www.readbyqxmd.com/read/28730727/better-arthritis-care-patients-expectations-and-priorities-the-competencies-that-community-based-health-professionals-need-to-improve-their-care-of-people-with-arthritis
#10
J Erwin, K Edwards, A Woolf, S Whitcombe, S Kilty
OBJECTIVE: The aim of the present study was to identify the competencies that patients think non-specialist community-based nurses and allied health professionals (AHPs) need to enable them to assess, care for and manage arthritis appropriately. METHODS: Four face-to-face focus groups were held with a total of 16 women and nine men with arthritis, to discuss the care they received from community-based health professionals, the skills and knowledge they expected from community-based health professionals and what they prioritized...
July 21, 2017: Musculoskeletal Care
https://www.readbyqxmd.com/read/28730648/calcineurin-inhibitor-withdrawal-or-tapering-for-kidney-transplant-recipients
#11
REVIEW
Krishna M Karpe, Girish S Talaulikar, Giles D Walters
BACKGROUND: Calcineurin inhibitors (CNI) can reduce acute transplant rejection and immediate graft loss but are associated with significant adverse effects such as hypertension and nephrotoxicity which may contribute to chronic rejection. CNI toxicity has led to numerous studies investigating CNI withdrawal and tapering strategies. Despite this, uncertainty remains about minimisation or withdrawal of CNI. OBJECTIVES: This review aimed to look at the benefits and harms of CNI tapering or withdrawal in terms of graft function and loss, incidence of acute rejection episodes, treatment-related side effects (hypertension, hyperlipidaemia) and death...
July 21, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28730644/fungiscope-%C3%A2-global-emerging-fungal-infection-registry
#12
Danila Seidel, Luisa A Durán Graeff, Maria J G T Vehreschild, Hilmar Wisplinghoff, Maren Ziegler, J Janne Vehreschild, Blasius Liss, Axel Hamprecht, Philipp Köhler, Zdenek Racil, Nikolay Klimko, Donald C Sheppard, Raoul Herbrecht, Anuradha Chowdhary, Oliver A Cornely, FungiScope Group
Rare invasive fungal diseases (IFD) are challenging for the treating physicians because of their unspecific clinical presentation, as well as the lack of standardised diagnostic and effective treatment strategies. Late onset of treatment and inappropriate medication is associated with high mortality, thus, urging the need for a better understanding of these diseases. The purpose of FungiScope(™) is to continuously collect clinical information and specimens to improve the knowledge on epidemiology and eventually improve patient management of these orphan diseases...
August 2017: Mycoses
https://www.readbyqxmd.com/read/28730475/characterization-of-ligand-binding-to-pseudokinases-using-a-thermal-shift-assay
#13
Isabelle S Lucet, James M Murphy
The protocol herein describes a robust and proven method for the measurement of pseudokinase-ligand interaction using a fluorescence-based thermal shift assay (TSA). Pseudokinases are kinase-like proteins that have recently emerged as crucial regulatory modules of signal transduction pathways and may well represent a novel class of drug targets. However, unlike kinases, the regulatory activity of pseudokinases is mainly conferred through protein-protein interactions. Understanding the mechanisms that underlie pseudokinase conformational changes through ligand binding and how such conformational changes can tune signaling pathways is a necessary step to unravel their biological functions...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28729199/violent-firearm-related-conflicts-among-high-risk-youth-an-event-level-and-daily-calendar-analysis
#14
Patrick M Carter, Maureen A Walton, Jason Goldstick, Quyen M Epstein-Ngo, Marc A Zimmerman, Melissa C Mercado, Amanda Garcia Williams, Rebecca M Cunningham
Firearm homicide is the leading cause of violence-related youth mortality. To inform prevention efforts, we analyzed event-level data to identify unique precursors to firearm conflicts. Youth (ages:14-24) seeking Emergency Department (ED) treatment for assault or for other reasons and reporting past 6-month drug use were enrolled in a 2-year longitudinal study. Time-line follow-back substance use/aggression modules were administered at baseline and each 6-month follow-up. Violent non-partner conflicts were combined across time-points...
July 17, 2017: Preventive Medicine
https://www.readbyqxmd.com/read/28728979/ploc-mvirus-predict-subcellular-localization-of-multi-location-virus-proteins-via-incorporating-the-optimal-go-information-into-general-pseaac
#15
Xiang Cheng, Xuan Xiao, Kuo-Chen Chou
Knowledge of subcellular locations of proteins is crucially important for in-depth understanding their functions in a cell. With the explosive growth of protein sequences generated in the postgenomic age, it is highly demanded to develop computational tools for timely annotating their subcellular locations based on the sequence information alone. The current study is focused on virus proteins. Although considerable efforts have been made in this regard, the problem is far from being solved yet. Most existing methods can be used to deal with single-location proteins only...
July 17, 2017: Gene
https://www.readbyqxmd.com/read/28728822/a-microfluidic-approach-for-studying-piezo-channels
#16
M M Maneshi, P A Gottlieb, S Z Hua
Microfluidics is an interdisciplinary field intersecting many areas in engineering. Utilizing a combination of physics, chemistry, biology, and biotechnology, along with practical applications for designing devices that use low volumes of fluids to achieve high-throughput screening, is a major goal in microfluidics. Microfluidic approaches allow the study of cells growth and differentiation using a variety of conditions including control of fluid flow that generates shear stress. Recently, Piezo1 channels were shown to respond to fluid shear stress and are crucial for vascular development...
2017: Current Topics in Membranes
https://www.readbyqxmd.com/read/28728496/a-missing-piece-in-clinical-trial-inspections-in-latin-america-interviews-with-research-subjects-in-peru
#17
Gabriela E Minaya, Duilio J Fuentes-Delgado, Antonio Ugalde, Núria Homedes
Most regulatory agencies conduct clinical trial (CT) site inspections, but the experiences and behaviors of the research subjects and their knowledge of the rights and obligations that ensue from participating in a CT are seldom explored. The authors assessed the technical feasibility of incorporating interviews with participants in CT inspections. This article analyzes the responses of 13 CT participants, 14% ( n = 96) of those included in three tuberculosis (TB) CTs. Participants did not object to being interviewed and provided information not obtained during regular inspections...
July 1, 2017: Journal of Empirical Research on Human Research Ethics: JERHRE
https://www.readbyqxmd.com/read/28728494/the-clinical-significance-of-qt-prolongation-associated-with-tamoxifen-a-review-of-the-literature
#18
Katherine Fung, Julia Imeson, Frances Cusano
Objective To review the literature discussing QT prolongation associated with the use of tamoxifen in order to evaluate the clinical significance. Data sources A search of PubMed (1946 to 2017), MEDLINE (1946 to 2017) and EMBASE (1947 to 2017) was performed using a combination of the following search terms: tamoxifen, estrogen antagonist, selective estrogen receptor modulator, QT prolongation, QT interval, long QT syndrome and torsades de pointes. All searches were limited to human subjects. Reference lists of the literature found were also reviewed but did not reveal any further articles...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28727843/atomistic-modeling-of-alternating-access-of-a-mitochondrial-adp-atp-membrane-transporter-with-molecular-simulations
#19
Koichi Tamura, Shigehiko Hayashi
The mitochondrial ADP/ATP carrier (AAC) is a membrane transporter that exchanges a cytosolic ADP for a matrix ATP. Atomic structures in an outward-facing (OF) form which binds an ADP from the intermembrane space have been solved by X-ray crystallography, and revealed their unique pseudo three-fold symmetry fold which is qualitatively different from pseudo two-fold symmetry of most transporters of which atomic structures have been solved. However, any atomic-level information on an inward-facing (IF) form, which binds an ATP from the matrix side and is fixed by binding of an inhibitor, bongkrekic acid (BA), is not available, and thus its alternating access mechanism for the transport process is unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28727677/surveillance-for-silicosis-deaths-among-persons-aged-15-44-years-united-states-1999-2015
#20
Jacek M Mazurek, John M Wood, Patricia L Schleiff, David N Weissman
Silicosis is usually a disease of long latency affecting mostly older workers; therefore, silicosis deaths in young adults (aged 15-44 years) suggests acute or accelerated disease.* To understand the circumstances surrounding silicosis deaths among young persons, CDC analyzed the underlying and contributing causes(†) of death using multiple cause-of-death data (1999-2015) and industry and occupation information abstracted from death certificates (1999-2013). During 1999-2015, among 55 pneumoconiosis deaths of young adults with International Classification of Diseases, Tenth Revision (ICD-10) code J62 (pneumoconiosis due to dust containing silica),(§) 38 (69%) had code J62...
July 21, 2017: MMWR. Morbidity and Mortality Weekly Report
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