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https://www.readbyqxmd.com/read/28101965/a-multi-hit-hypothesis-of-bullous-pemphigoid-and-associated-neurological-disease-is-hla-dqb1-03-01-a-potential-link-between-immune-privileged-antigen-exposure-and-epitope-spreading
#1
REVIEW
K T Amber, J Zikry, M Hertl
Bullous pemphigoid (BP) is the most common autoimmune blistering disease and is linked to IgG recognition of 2 hemidesmosomal antigens, that is, BP230 (BP antigen 1) and BP180 (BP antigen 2, collagen XVII). The association of BP with other systemic diseases, particularly neurocognitive diseases, provides a potential clue in the underlying pathogenesis of BP. The role of HLA-DQB1*03:01 binding to the immunogenic portion of BP180 provides a potential mechanism by which exposure to neuronal collagen BP180 may lead to cutaneous disease...
January 19, 2017: HLA
https://www.readbyqxmd.com/read/28101126/characterisation-of-microbial-communities-within-aggressive-prostate-cancer-tissues
#2
Melissa A Yow, Sepehr N Tabrizi, Gianluca Severi, Damien M Bolton, John Pedersen, Graham G Giles, Melissa C Southey
BACKGROUND: An infectious aetiology for prostate cancer has been conjectured for decades but the evidence gained from questionnaire-based and sero-epidemiological studies is weak and inconsistent, and a causal association with any infectious agent is not established. We describe and evaluate the application of new technology to detect bacterial and viral agents in high-grade prostate cancer tissues. The potential of targeted 16S rRNA gene sequencing and total RNA sequencing was evaluated in terms of its utility to characterise microbial communities within high-grade prostate tumours...
2017: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/28100506/twittering-on-about-mental-health-is-it-worth-the-effort
#3
Mahesh Jayaram, Lindsay Moran, Clive Adams
The medical community disseminates information increasingly using social media. Randomised controlled trials are being conducted in this area to evaluate effectiveness of social media with mixed results so far, but more trials are likely to be published in the coming years. One recent twitter randomised control trial using Cochrane Schizophrenia Group reviews suggests that tweets increase the hits to the target web page by about threefold and time spent on the web page is also increased threefold when referrals come in via twitter...
January 18, 2017: Evidence-based Mental Health
https://www.readbyqxmd.com/read/28100301/high-throughput-screening-of-a-glaxosmithkline-protein-kinase-inhibitor-set-identifies-an-inhibitor-of-human-cytomegalovirus-replication-that-prevents-creb-and-histone-h3-post-translational-modification
#4
Amina S Khan, Matthew J Murray, Catherine M K Ho, William J Zuercher, Matthew B Reeves, Blair L Strang
To identify new compounds with anti-human cytomegalovirus (HCMV) activity and new anti-HCMV targets, we developed a high throughput strategy to screen a GlaxoSmithKline (GSK) Published Kinase Inhibitor Set (PKIS). This collection contains a range of extensively characterized compounds grouped into chemical families (chemotypes). From our screen we identified compounds within chemotypes that impede HCMV replication and identified kinase proteins associated with inhibition of HCMV replication that are potential novel anti-HCMV targets...
January 18, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28097765/a-false-positive-screening-hit-in-fragment-based-lead-discovery-watch-out-for-the-red-herring
#5
Jonathan Cramer, Johannes Schiebel, Tobias Wulsdorf, Kristof Grohe, Eszter Eva Najbauer, Frederik R Ehrmann, Nedyalka Radeva, Nina Zitzer, Uwe Linne, Rasmus Linser, Andreas Heine, Gerhard Klebe
With the rising popularity of fragment-based approaches in drug development, more and more attention has to be devoted to the detection of false-positive screening results. In particular, the small size and low affinity of fragments drives screening techniques to their limit. The pursuit of a false-positive hit can cause significant loss of time and resources. Here, we present an instructive and intriguing investigation into the origin of misleading assay results for a fragment that emerged as the most potent binder for the aspartic protease endothiapepsin (EP) across multiple screening assays...
January 18, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28097705/non-polar-lipids-accumulate-during-storage-of-transfusion-products-and-do-not-contribute-to-the-onset-of-transfusion-related-acute-lung-injury
#6
A L Peters, M A T Vervaart, R van Bruggen, D de Korte, R Nieuwland, W Kulik, A P J Vlaar
BACKGROUND AND OBJECTIVES: The accumulation of non-polar lipids arachidonic acid, 5-hydroxyeicosatetraenoic acid (HETE), 12-HETE and 15-HETE during storage of transfusion products may play a role in the onset of transfusion-related acute lung injury (TRALI), a syndrome of respiratory distress after transfusion. MATERIALS AND METHODS: We investigated non-polar lipid accumulation in red blood cells (RBCs) stored for 42 days, plasma stored for 7 days at either 4 or 20°C and platelet (PLT) transfusion products stored for 7 days...
January 2017: Vox Sanguinis
https://www.readbyqxmd.com/read/28097521/alcohol-consumption-and-dementia-risk-a-dose-response-meta-analysis-of-prospective-studies
#7
Wei Xu, Huifu Wang, Yu Wan, Chenchen Tan, Jieqiong Li, Lan Tan, Jin-Tai Yu
It is widely believed that light-to-moderate alcohol intake may protect against dementia while excessive drinking may instead increase the risk. Nonetheless, these findings need cautious interpretations due to varying methodologies and lack of standard definition, which hindered our transferring into preventative practice. The objective of this study is to investigate the potential dose-response association between alcohol consumption and risk of dementia. A systematic search was conducted in electronic databases to identify relevant studies...
January 17, 2017: European Journal of Epidemiology
https://www.readbyqxmd.com/read/28097287/using-active-learning-to-identify-health-information-technology-related-patient-safety-events
#8
Allan Fong, Jessica L Howe, Katharine T Adams, Raj M Ratwani
The widespread adoption of health information technology (HIT) has led to new patient safety hazards that are often difficult to identify. Patient safety event reports, which are self-reported descriptions of safety hazards, provide one view of potential HIT-related safety events. However, identifying HIT-related reports can be challenging as they are often categorized under other more predominate clinical categories. This challenge of identifying HIT-related reports is exacerbated by the increasing number and complexity of reports which pose challenges to human annotators that must manually review reports...
January 18, 2017: Applied Clinical Informatics
https://www.readbyqxmd.com/read/28095475/the-influence-of-community-health-resources-on-effectiveness-and-sustainability-of-community-and-lay-health-worker-programs-in-lower-income-countries-a-systematic-review
#9
Daniel H de Vries, Robert Pool
BACKGROUND: Despite the availability of practical knowledge and effective interventions required to reduce priority health problems in low-income countries, poor and vulnerable populations are often not reached. One possible solution to this problem is the use of Community or Lay Health Workers (CLHWs). So far, however, the development of sustainability in CLHW programs has failed and high attrition rates continue to pose a challenge. We propose that the roles and interests which support community health work should emerge directly from the way in which health is organized at community level...
2017: PloS One
https://www.readbyqxmd.com/read/28095082/effect-of-concussion-on-performance-of-national-football-league-players
#10
Nicole Reams, Rodney A Hayward, Jeffrey S Kutcher, James F Burke
PURPOSE: Lingering neurologic injury after concussion may expose athletes to increased risk if return-to-play is premature. We explored whether on-field performance after concussion is a marker of lingering neurologic injury. METHODS: Retrospective cohort study on 1,882 skill-position players who played in the National Football League (NFL) during 2007-2010. Players with concussion based on the weekly injury report, were compared to players with other head and neck injuries (controls) on measures of on-field performance using Football Outsiders' calculation of Defense-Adjusted Yards Above Replacement (DYAR): a measure of a player's contribution controlling for game context...
January 17, 2017: International Journal of Sports Physiology and Performance
https://www.readbyqxmd.com/read/28095027/severe-and-extensive-traumatic-axonal-injury-following-minor-and-indirect-head-trauma
#11
Sung Ho Jang, Han Do Lee
OBJECTIVES: This study reports on a patient with mild traumatic brain injury (TBI) who showed severe and extensive traumatic axonal injury (TAI) of various neural tracts following minor and indirect head trauma, which was demonstrated by diffusion tensor tractography (DTT). CASE DESCRIPTION: A 26-year-old female patient suffered from indirect head trauma resulting from flexion-hyperextension injury after being hit from behind by a slowly moving car. At the time of head trauma, she felt tingling sensation on her four extremities; however, she did not experience loss of consciousness...
January 17, 2017: Brain Injury: [BI]
https://www.readbyqxmd.com/read/28094913/inhibition-of-pax2-transcription-activation-with-a-small-molecule-that-targets-the-dna-binding-domain
#12
Edward Grimley, Chenzhong Liao, Egon J Ranghini, Zaneta Nikolovska-Coleska, Gregory R Dressler
The Pax gene family encodes DNA binding transcription factors that control critical steps in embryonic development and differentiation of specific cell lineages. Often, Pax proteins are re-expressed or ectopically expressed in cancer and other diseases of abnormal proliferation, making them attractive targets for tissue specific inhibition by small molecules. In this report, we used a homology model of the Pax2 paired domain and a virtual screen to identify small molecules that can inhibit binding of the paired domain to DNA and Pax2 mediated transcription activation...
January 17, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28094839/improved-fluorescence-assays-to-measure-the-defects-associated-with-f508del-cftr-allow-identification-of-new-active-compounds
#13
Emily Langron, Michela I Simone, Clémence M S Delalande, Jean-Louis Reymond, David L Selwood, Paola Vergani
BACKGROUND AND PURPOSE: Cystic fibrosis (CF) is a debilitating disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which codes for a Cl-/HCO3 - channel. F508del, the most common CF-associated mutation, causes both gating and biogenesis defects in the CFTR protein. This paper describes the optimisation of two fluorescence assays, capable of measuring CFTR function and cellular localisation, and their use in a pilot drug screen. EXPERIMENTAL APPROACH: HEK293 cells expressing YFP-F508del-CFTR, in which halide sensitive YFP is tagged to the N-terminal of CFTR, were used to screen a small library of compounds based on the VX-770 scaffold...
January 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28094183/discovering-novel-7-azaindole-based-series-as-potent-axl-kinase-inhibitors
#14
Clémence Feneyrolles, Léa Guiet, Mathilde Singer, Nathalie Van Hijfte, Bénédicte Daydé-Cazals, Bénédicte Fauvel, Gwénaël Chevé, Abdelaziz Yasri
AXL is a receptor tyrosine kinase that plays a key role in tumor growth and proliferation. The scientific community has validated AXL as therapeutic target in the treatment of cancers for several years now, and several AXL inhibitors have been developed but none of them are approved. In this context, we started to design new kinase inhibitors targeting AXL from the 7-azaindole scaffold well known to interact with the ATP binding site of the kinase. Focused screening and chemical diversification around 7-azaindole scaffold were developed, based on modeling studies and medicinal chemistry rational, leading to the discovery of a new family of hits with potent inhibitory activity against AXL...
January 9, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28093673/metagenomic-insights-into-effects-of-spent-engine-oil-perturbation-on-the-microbial-community-composition-and-function-in-a-tropical-agricultural-soil
#15
Lateef B Salam, Sunday O Obayori, Francisca O Nwaokorie, Aisha Suleiman, Raheemat Mustapha
Analyzing the microbial community structure and functions become imperative for ecological processes. To understand the impact of spent engine oil (SEO) contamination on microbial community structure of an agricultural soil, soil microcosms designated 1S (agricultural soil) and AB1 (agricultural soil polluted with SEO) were set up. Metagenomic DNA extracted from the soil microcosms and sequenced using Miseq Illumina sequencing were analyzed for their taxonomic and functional properties. Taxonomic profiling of the two microcosms by MG-RAST revealed the dominance of Actinobacteria (23...
January 16, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28093394/angry-gps-hit-back-at-pm-over-seven-day-service-threats
#16
Gareth Iacobucci
No abstract text is available yet for this article.
January 16, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28093338/a-virus-like-particle-vaccination-strategy-expands-its-tolerance-to-h3n2-antigenic-drift-by-enhancing-neutralizing-antibodies-against-hemagglutinin-stalk
#17
Ji-Rong Yang, Chieh-Yu Cheng, Chih-Yuan Chen, Chao-Hua Lin, Chuan-Yi Kuo, Hsiang-Yi Huang, Fu-Ting Wu, Yu-Chih Yang, Chia-Ying Wu, Ming-Tsan Liu, Pei-Wen Hsiao
Seasonal influenza viruses impact public health annually due to their continual evolution. However, the current inactivated seasonal vaccines provide poor protection against antigenically drifted viruses and require periodical reformulation through hit-and-miss predictions about which strains will circulate during the next season. To reduce the impact caused by vaccine mismatch, we investigated the drift-tolerance of virus-like particles (VLP) as an improved vaccine candidate. The cross-protective humoral immunity elicited by the H3N2-VLP vaccine constructed for the 2011-2012 season was examined against viruses isolated from 2010 to 2015 in Taiwan evolving chronologically through clades 1, 4, 5, 3B and 3C, as well as viruses that were circulating globally in 2005, 2007 and 2009...
January 13, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28092830/trpv1-antagonism-by-piperazinyl-aryl-compounds-a-topomer-comfa-study-and-its-use-in-virtual-screening-for-identification-of-novel-antagonists
#18
Rajendra Kristam, Shashidhar N Rao, Anne Sudha D'Cruz, Vijayalakshmi Mahadevan, Vellarkad N Viswanadhan
Transient Receptor Potential Vanilloid, member 1 (TRPV1), is a non-selective cation channel belonging to the transient receptor potential (TRP) family of ion channels. It occurs in the peripheral and central nervous system, activated by a variety of exogenous and endogenous stimuli, thus playing a key role in transmission of pain. This has been a target for chronic pain since more than a decade and a number of antagonists that progressed into clinical trials have failed due to the unexpected side effect of core body temperature rise, thus halting progress in this field...
January 7, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28092460/a-three-dimensional-lymphatic-endothelial-cell-tube-formation-assay-to-identify-novel-kinases-involved-in-lymphatic-vessel-remodeling
#19
T Jessica Gambino, Steven P Williams, Carol Caesar, Daniel Resnick, Cameron J Nowell, Rae H Farnsworth, Marc G Achen, Steven A Stacker, Tara Karnezis
The lymphatic system is a series of vessels that transport cells and excess fluid from tissues to the blood vascular system. Normally quiescent, the lymphatics can grow or remodel in response to developmental, immunological, or cells pathological stimuli. Lymphatic vessels comprise lymphatic endothelial cells (LECs) that can respond to external growth factors by undergoing proliferation, migration, adhesion, and tube and lumen formation into new vessel structures, a process known as lymphangiogenesis. To understand the key gene and signaling pathways necessary for lymphangiogenesis and lymphatic vessel remodeling, we have developed a three-dimensional LEC tube formation assay to explore the role of kinase signaling in these processes...
January 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28092278/delayed-onset-central-pain-due-to-degeneration-of-ischemic-transcallosal-fibers-after-corpus-callosum-hemorrhage
#20
Sung Ho Jang, Chul Hoon Chang, Young Jin Jung, Han Do Lee
AIMS: A patient developed delayed-onset central pain due to degeneration of the spinothalamic tract resulting from degeneration of the ischemic transcallosal fibers, in the aftermath of a corpus callosum (CC) hemorrhage. The detection and diagnosis of these lesions using diffusion tensor tractography are described. METHODS: A 59-yr-old man underwent conservative management for hemorrhages in the CC and lateral ventricle that resulted from hitting his head against a wall while falling...
January 13, 2017: American Journal of Physical Medicine & Rehabilitation
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