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Sabrina J Merat, Richard Molenkamp, Koen Wagner, Sylvie M Koekkoek, Dorien van de Berg, Etsuko Yasuda, Martino Böhne, Yvonne B Claassen, Bart P Grady, Maria Prins, Arjen Q Bakker, Menno D de Jong, Hergen Spits, Janke Schinkel, Tim Beaumont
Hepatitis C virus (HCV) is world-wide a major cause of liver related morbidity and mortality. No vaccine is available to prevent HCV infection. To design an effective vaccine, understanding immunity against HCV is necessary. The memory B cell repertoire was characterized from an intravenous drug user who spontaneously cleared HCV infection 25 years ago. CD27+IgG+ memory B cells were immortalized using BCL6 and Bcl-xL. These immortalized B cells were used to study antibody-mediated immunity against the HCV E1E2 glycoproteins...
2016: PloS One
Florian Stefanov, Tim McGloughlin, Liam Morris
There are several issues attributed with abdominal aortic aneurysm endovascular repair. The positioning of bifurcated stent-grafts (SG) may affect SG hemodynamics. The hemodynamics and geometrical parameters of crossing or non-crossing graft limbs have not being totally accessed. Eight patient-specific SG devices and four pre-operative cases were computationally simulated, assessing the hemodynamic and geometrical effects for crossed (n= 4) and non-crossed (n= 4) configurations. SGs eliminated the occurrence of significant recirculations within the sac prior treatment...
October 20, 2016: Medical Engineering & Physics
Yi Yong, Ammar Saleem, José A Guerrero-Analco, Pierre S Haddad, Alain Cuerrier, John T Arnason, Cory S Harris, Tim Johns
ETHNOPHARMACOLOGICAL RELEVANCE: Larix laricina, a native tree of North America, is a highly respected medicinal plant used for generations by Indigenous Peoples across its range, including the Cree of northern Québec who use the bark to treat symptoms of diabetes. This study investigates the antioxidant capacity and bioavailability of active constituents identified in L. laricina bark extracts. MATERIALS AND METHODS: (1) Oxygen radical absorbance capacity (ORAC) assay was employed to test antioxidant capacity of organic extracts (80% ethanol) from bark of L...
October 20, 2016: Journal of Ethnopharmacology
Sonia Johnson, Luke Sheridan Rains, Steven Marwaha, John Strang, Thomas Craig, Tim Weaver, Paul McCrone, Michael King, David Fowler, Stephen Pilling, Louise Marston, Rumana Z Omar, Meghan Craig, Mark Hinton
BACKGROUND: Around 35-45 % of people in contact with services for a first episode of psychosis are using cannabis. Cannabis use is associated with delays in remission, poorer clinical outcomes, significant increases in the risk of relapse, and lower engagement in work or education. While there is a clear need for effective interventions, so far only very limited benefits have been achieved from psychological interventions. Contingency management (CM) is a behavioural intervention in which specified desired behavioural change is reinforced through financial rewards...
October 22, 2016: Trials
Karen P Hayhurst, Matthias Pierce, Matthew Hickman, Toby Seddon, Graham Dunn, John Keane, Tim Millar
BACKGROUND: Although evidence points to a strong link between illicit drug use and crime, robust evidence for temporal order in the relationship is scant. We carried out a systematic review to assess the evidence for pathways through opiate/crack cocaine use and offending to determine temporal order. METHODS: A systematic review sourced five databases, three online sources, bibliographies and citation mapping. Inclusion criteria were: focus on opiate/crack use, and offending; pre-drug use information; longitudinal design; corroborative official crime records...
October 19, 2016: International Journal on Drug Policy
Raymond Kwok Kei Chow, Sarah Tsz-Kwan Sin, Ming Liu, Yan Li, Tim Hon Man Chan, Yangyang Song, Leilei Chen, Dora Lai-Wan Kwong, Xin-Yuan Guan
Hepatocellular carcinoma (HCC), which accounts for 85-90% of primary liver cancer, is now the second leading cause of cancer-related mortality worldwide. Here we reported that Aldo-Keto Reductase family 7A isoform 3 (AKR7A3) is frequently down-regulated in HCC, associating with poor overall survival rate, elevated serum α-fetoprotein (AFP) and poor differentiation of HCC. The promoter region of AKR7A3 was detected to be hypermethylated. Loss of heterozygosity (LOH) was also detected in AKR7A3. Functional assays on both AKR7A3 overexpressed and knockdown cells, including foci formation, colony formation in soft agar, migration, invasion and tumor formation in nude mice, demonstrated the strong tumor suppressive functions of AKR7A3...
October 18, 2016: Oncotarget
Siroon Bekkering, Inge van den Munckhof, Tim Nielen, Evert Lamfers, Charles Dinarello, Joost Rutten, Jacqueline de Graaf, Leo A B Joosten, Mihai G Netea, Marc E R Gomes, Niels P Riksen
BACKGROUND AND AIMS: We have recently reported that monocytes can undergo functional and transcriptional reprogramming towards a long-term pro-inflammatory phenotype after brief in vitro exposure to atherogenic stimuli such as oxidized LDL. This process is termed 'trained immunity', and is mediated by epigenetic remodeling and a metabolic switch towards increased aerobic glycolysis. We hypothesize that trained immunity contributes to atherogenesis. Therefore, we investigated the inflammatory phenotype and epigenetic remodeling of monocytes from patients with and without established atherosclerosis...
October 12, 2016: Atherosclerosis
Johan van der Meer, André Pampel, Eus van Someren, Jennifer Ramautar, Ysbrand van der Werf, German Gomez-Herrero, Jöran Lepsien, Lydia Hellrung, Hermann Hinrichs, Harald Möller, Martin Walter
This data set contains electroencephalography (EEG) data as well as simultaneous EEG with functional magnetic resonance imaging (EEG/fMRI) data. During EEG/fMRI, the EEG cap was outfitted with a hardware-based add-on consisting of carbon-wire loops (CWL). These yielded six extra׳CWL׳ signals related to Faraday induction of these loops in the main magnetic field "Measurement and reduction of motion and ballistocardiogram artefacts from simultaneous EEG and fMRI recordings" (Masterton et al., 2007) [1]. In this data set, the CWL data make it possible to do a direct regression approach to deal with the BCG and specifically He artifact...
June 2016: Data in Brief
Xingwei Jiang, Tingting Zhou, Yan Xiao, Jiahui Yu, Shuaijie Dou, Guojiang Chen, Renxi Wang, He Xiao, Chunmei Hou, Wei Wang, Qingzhu Shi, Jiannan Feng, Yuanfang Ma, Beifen Shen, Yan Li, Gencheng Han
T cell Ig mucin-3 (Tim-3), an immune checkpoint inhibitor, shows therapeutic potential. However, the molecular mechanism by which Tim-3 regulates immune responses remains to be determined. In particular, very little is known about how Tim-3 works in innate immune cells. Here, we demonstrated that Tim-3 is involved in the development of tumor-promoting M2 macrophages in colon cancer. Manipulation of the Tim-3 pathway significantly affected the polarization status of intestinal macrophages and the progression of colon cancer...
2016: Oncoimmunology
Laura Anselmi, Rachel Meacock, Søren Rud Kristensen, Tim Doran, Matt Sutton
BACKGROUND: Studies finding higher mortality rates for patients admitted to hospital at weekends rely on routine administrative data to adjust for risk of death, but these data may not adequately capture severity of illness. We examined how rates of patient arrival at accident and emergency (A&E) departments by ambulance-a marker of illness severity-were associated with in-hospital mortality by day and time of attendance. METHODS: Retrospective observational study of 3 027 946 admissions to 140 non-specialist hospital trusts in England between April 2013 and February 2014...
October 18, 2016: BMJ Quality & Safety
Iris J H van Vlodrop, Sophie C Joosten, Tim de Meyer, Kim M Smits, Leander Van Neste, Veerle Melotte, Marcella Baldewijns, Leo J Schouten, Piet A van den Brandt, Jana Jeschke, Joo Mi Yi, Kornel Schuebel, Nita Ahuja, James G Herman, Maureen Aarts, Fred T Bosman, Wim Van Criekinge, Manon van Engeland
PURPOSE: The currently used prognostic models for patients with non-metastatic clear cell renal cell carcinoma (ccRCC) are based on clinicopathological features and might be improved by adding molecular markers. Epigenetic alterations occur frequently in ccRCC and are promising biomarkers. The aim of this study is to identify prognostic promoter methylation markers for ccRCC. EXPERIMENTAL DESIGN: We integrated data generated by massive parallel sequencing of methyl-binding domain enriched DNA and microarray based RNA expression profiling of 5-aza-2'-deoxycytidine treated ccRCC cell lines to comprehensively characterize the ccRCC methylome...
October 18, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Sarah Mahoney, Ruth M Sladek, Tim Neild
BACKGROUND: Although appropriate empathy in health professionals is essential, a loss of empathy can occur during medical education. The structure of clinical learning may be one factor that is implicated in a loss of empathy. This study examines student and doctor empathy, and possible associations between empathy and the structure of clinical learning. METHODS: There were three groups of participants: medical students (n = 281), who completed a longitudinal survey consisting of the Jefferson Scale of Empathy and an open question about empathy at the beginning and end of the 2013 academic year; private doctors (medical practitioners) in South Australia (n = 78) who completed a survey consisting of the Jefferson Scale of Empathy and an open question about empathy at the end of the students' academic year; and doctors (medical practitioners) from public teaching hospitals (n = 72) in southern Adelaide, South Australia who completed a survey consisting of the Jefferson Scale of Empathy at the end of the students' academic year ...
October 18, 2016: BMC Medical Education
Obdulia Rabal, Fernando Pastor, Helena Villanueva, Mario M Soldevilla, Sandra Hervas-Stubbs, Julen Oyarzabal
Complementing Systematic Evolution of Ligands by EXponential Enrichment (SELEX) technologies with in silico prediction of aptamer binders has attracted a lot of interest in the recent years. We propose a workflow involving 2D structure prediction, 3D RNA modeling using Rosetta and docking to the target protein with 3dRPC for: (i) prediction of the binding mode of our two previously reported potent (Kd < 50 nmol/l) murine TIM3 aptamers, and (ii) the prioritization of TIM3 aptamers that were enriched in the SELEX workflow...
October 18, 2016: Molecular Therapy. Nucleic Acids
Daniel F Hanley, Richard E Thompson, John Muschelli, Michael Rosenblum, Nichol McBee, Karen Lane, Amanda J Bistran-Hall, Steven W Mayo, Penelope Keyl, Dheeraj Gandhi, Tim C Morgan, Natalie Ullman, W Andrew Mould, J Ricardo Carhuapoma, Carlos Kase, Wendy Ziai, Carol B Thompson, Gayane Yenokyan, Emily Huang, William C Broaddus, R Scott Graham, E Francois Aldrich, Robert Dodd, Cristanne Wijman, Jean-Louis Caron, Judy Huang, Paul Camarata, A David Mendelow, Barbara Gregson, Scott Janis, Paul Vespa, Neil Martin, Issam Awad, Mario Zuccarello
BACKGROUND: Craniotomy, according to the results from trials, does not improve functional outcome after intracerebral haemorrhage. Whether minimally invasive catheter evacuation followed by thrombolysis for clot removal is safe and can achieve a good functional outcome is not known. We investigated the safety and efficacy of alteplase, a recombinant tissue plasminogen activator, in combination with minimally invasive surgery (MIS) in patients with intracerebral haemorrhage. METHODS: MISTIE was an open-label, phase 2 trial that was done in 26 hospitals in the USA, Canada, the UK, and Germany...
November 2016: Lancet Neurology
Tim Smeets, Florence van Hunsel
A 38-year-old male and a 36-year-old female experienced red-brown urine discolouration after 2 and 3 days, respectively, during the use of mesalamine for inflammatory bowel disease. Both patients mentioned that the urine discoloured after contact with sodium hypochlorite detergent in toilet water. Mesalamine and the inactive metabolite N-acetyl-5-aminosalicylic acid are primarily excreted in the urine. We hypothesised a possible reaction with sodium hypochlorite and/or light. Naranjo assessment scores of 9 and 6 were obtained for the reports, indicating a certain and probable relationship, respectively, between the red-brown urine discolouration and the use of the suspect drug mesalamine...
December 2016: Drug Saf Case Rep
Donna N Petersen, Julie Hawkins, Wanida Ruangsiriluk, Kimberly A Stevens, Bruce A Maguire, Thomas N O'Connell, Benjamin N Rocke, Markus Boehm, Roger B Ruggeri, Tim Rolph, David Hepworth, Paula M Loria, Philip A Carpino
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that downregulates low-density lipoprotein (LDL) receptor (LDL-R) levels on the surface of hepatocytes, resulting in decreased clearance of LDL-cholesterol (LDL-C). Phenotypic screening of a small-molecule compound collection was used to identify an inhibitor of PCSK9 secretion, (R)-N-(isoquinolin-1-yl)-3-(4-methoxyphenyl)-N-(piperidin-3-yl)propanamide (R-IMPP), which was shown to stimulate uptake of LDL-C in hepatoma cells by increasing LDL-R levels, without altering levels of secreted transferrin...
October 13, 2016: Cell Chemical Biology
Tim Leschinger, Patric Raiss, Markus Loew, Felix Zeifang
BACKGROUND: This study evaluated and identified risk factors for the development of intraoperative and postoperative surgical complications in total shoulder arthroplasty in patients with primary osteoarthritis. METHODS: We evaluated patient-specific factors, including age, sex, body mass index, prior nonarthroplasty surgery, smoking, alcohol consumption, and the American Society of Anesthesiologists (ASA) Physical Status Classification System in 275 patients (76 men, 199 women) with an average age of 68 years (range, 51-85 years)...
October 10, 2016: Journal of Shoulder and Elbow Surgery
Marcus Nyström, Diederick C Niehorster, Tim Cornelissen, Henrik Garde
Technological advancements in combination with significant reductions in price have made it practically feasible to run experiments with multiple eye trackers. This enables new types of experiments with simultaneous recordings of eye movement data from several participants, which is of interest for researchers in, e.g., social and educational psychology. The Lund University Humanities Laboratory recently acquired 25 remote eye trackers, which are connected over a local wireless network. As a first step toward running experiments with this setup, demanding situations with real time sharing of gaze data were investigated in terms of network performance as well as clock and screen synchronization...
October 14, 2016: Behavior Research Methods
Marcus R Makowski, Christian H P Jansen, Ullrich Ebersberger, Tobias Schaeffter, Reza Razavi, Massimo Mangino, Tim D Spector, Rene M Botnar, Gerald F Greil
OBJECTIVES: The aim of this study was to investigate the impact of BMI on late gadolinium enhancement (LGE) of the coronary artery wall in identical monozygous twins discordant for BMI. Coronary LGE represents a useful parameter for the detection and quantification of atherosclerotic coronary vessel wall disease. METHODS: Thirteen monozygote female twin pairs (n = 26) with significantly different BMIs (>1.6 kg/m2) were recruited out of >10,000 twin pairs (TwinsUK Registry)...
October 14, 2016: European Radiology
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