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Paradigm shift

Chikondi A Mwendera, Christiaan de Jager, Herbert Longwe, Kamija Phiri, Charles Hongoro, Clifford M Mutero
BACKGROUND: Research on various determinants of health is key in providing evidence for policy development, thereby leading to successful interventions. Utilization of research is an intricate process requiring an understanding of contextual factors. The study was conducted to assess enhancing factors and barriers of research utilization for malaria policy development in Malawi. METHODS: Qualitative research approach was used through in-depth interviews with 39 key informants that included malaria researchers, policy makers, programme managers, and key stakeholders...
October 19, 2016: Malaria Journal
Wei Dong, Elizabeth S Olson
Cochlear frequency tuning is based on a mildly tuned traveling-wave response that is enhanced in amplitude and sharpness by outer hair cell (OHC)-based forces. The nonlinear and active character of this enhancement is the fundamental manifestation of cochlear amplification. Recently, mechanical (pressure) and electrical (extracellular OHC-generated voltage) responses were simultaneously measured close to the sensory tissue's basilar membrane. Both pressure and voltage were tuned and showed traveling-wave phase accumulation, evidence that they were locally generated responses...
October 18, 2016: Biophysical Journal
Hani N Sabbah
Introduction Heart failure (HF) has reached epidemic proportions worldwide. Despite the availability of drugs that reduce mortality and afford good symptom relief, HF continues to exact a considerable clinical and economic burden. Current HF therapies elicit benefit by reducing cardiac workload by lowering heart rate and loading conditions, thereby reducing myocardial energy demands. Areas covered Recent recognition that the failing heart is "energy deprived" and its primary energy source, the mitochondria, is dysfunctional, has focused attention on mitochondria as a worthy therapeutic target...
October 19, 2016: Expert Review of Cardiovascular Therapy
Suravi Patra
No abstract text is available yet for this article.
July 2016: Indian Journal of Pharmacology
Dominique Van de Velde, Ank Eijkelkamp, Wim Peersman, Patricia De Vriendt
BACKGROUND: Over the past decades, there has been a paradigm shift from a purely biomedical towards a bio-psycho-social (BPS) conception of disability and illness, which has led to a change in contemporary healthcare. However, there seems to be a gap between the rhetoric and reality of working within a BPS model. It is not clear whether healthcare professionals show the necessary skills and competencies to act according to the BPS model. OBJECTIVE: The aim of this study was (1) to develop a scale to monitor the BPS competencies of healthcare professionals, (2) to define its factor-structure, (3) to check internal consistency, (4) test-retest reliability and (5) feasibility...
2016: PloS One
Matthew R Louis, Larry H Hollier
No abstract text is available yet for this article.
October 14, 2016: Journal of Craniofacial Surgery
David Legouis, Pierre Galichon, Aurélien Bataille, Sylvie Chevret, Sophie Provenchère, Anne Boutten, Dimitrios Buklas, Jean-Luc Fellahi, Jean-Luc Hanouz, Alexandre Hertig
BACKGROUND: There is recent evidence to show that patients suffering from acute kidney injury are at increased risk of developing chronic kidney disease despite the fact that surviving tubular epithelial cells have the capacity to fully regenerate renal tubules and restore renal function within days or weeks. The aim of the study was to investigate the impact of acute kidney injury on de novo chronic kidney disease. METHODS: The authors conducted a retrospective population-based cohort study of patients initially free from chronic kidney disease who were scheduled for elective cardiac surgery with cardiopulmonary bypass and who developed an episode of acute kidney injury from which they recovered...
October 17, 2016: Anesthesiology
James Scholey
The classical view of the RAS is a linear signaling pathway beginning with the conversion of angiotensinogen to ANG I by renin, an enzyme secreted by the kidney. ANG I is converted to ANG II by angiotensin converting enzyme (ACE) ANG II binds to the G-protein coupled angiotensin II receptor type 1. The RAS is a circulating system but we now know that the RAS is also locally expressed in a number of tissues, including the kidneys and the heart. ANG II exerts adverse hemodynamic and non-hemodynamic effects on renal cells...
September 2016: Journal of Hypertension
ByungSu Yoo
Heart failure (HF) represents a significant healthcare issue because of its ever-increasing prevalence, poor prognosis and complex pathophysiology. The cornerstone of modern drug therapy in chronic HF is the inhibition of neurohormonal activation that plays a crucial role in the pathophysiology of HF development and progression and, more specifically, of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system. LCZ696 is a first-in-class, angiotensin receptor NEP inhibitor (ARNI) that consists of a supramolecular complex of a molecule of the ARB valsartan in combination with a molecule of the NEP inhibitor prodrug AHU377 (also known as sacubitril)...
September 2016: Journal of Hypertension
Hilaire C Lam, Julie S Nijmeh, Elizabeth P Henske
In just the past five years, dramatic changes have occurred in the clinical management of Tuberous Sclerosis Complex (TSC). Detailed knowledge about the role of the TSC proteins in regulating the activity of the mammalian Target of Rapamycin Complex 1 (mTORC1) underlies this paradigm-shifting progress. Advances continue to be made in understanding the genetic pathogenesis of the different tumours that occur in TSC, including pivotal discoveries using next-generation sequencing (NGS). For example, the pathogenesis of angiofibromas is now known to involve UV-induced mutations, and the pathogenesis of multifocal renal cell carcinoma (RCC) in TSC is now known to result from distinct second-hit mutations...
October 18, 2016: Journal of Pathology
Ulrich Förstner, Henner Hollert, Markus Brinkmann, Kathrin Eichbaum, Roland Weber, Wim Salomons
A critical review of the last 25 years of dioxin policy in the Elbe river catchment is presented along seven main theses of the River Basin Community (RBC)-Elbe background document "Pollutants" for the Management Plan 2016-2021. In this period, polychlorinated dibenzodioxins/-furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs) will play a major role: (i) as new priority substances for which environmental quality standards (EQSs) need to be derived (Directive 2013/39/EC); (ii) in the search for innovative solutions in sediment remediation (i...
2016: Environmental Sciences Europe
Garabed Eknoyan
Diseases of the kidney are old, but the discipline dedicated to their study, nephrology, is barely more than 50 years old. As recounted in this recollection of those events, the rudiments of what would become nephrology emerged in the time between the 2 World Wars from basic studies of normal kidney function and flourished after the integration of their methodologies into clinical medicine thereafter. Although shaped by studies of kidney function in the 1960s, it was the subsequent advent of dialysis that fueled the growth of nephrology well into the 21st century...
October 14, 2016: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
Chiara Fraccaro, Giuseppe Tarantini
No abstract text is available yet for this article.
September 2016: Journal of Thoracic Disease
Ming-Shan Wang, Yong-Xia Huo, Yan Li, Newton O Otecko, Ling-Yan Su, Hai-Bo Xu, Shi-Fang Wu, Min-Sheng Peng, He-Qun Liu, Lin Zeng, David M Irwin, Yong-Gang Yao, Dong-Dong Wu, Ya-Ping Zhang
Body size is the most important economic trait for animal production and breeding. Several hundreds of loci have been reported to be associated with growth trait and body weight in chickens. The loci are mapped to large genomic regions due to the low density and limited number of genetic markers in previous studies. Herein, we employed comparative population genomics to identify genetic basis underlying the small body size of Yuanbao chicken (a famous ornamental chicken) based on 89 whole genomes. The most significant signal was mapped to the BMP10 gene, whose expression was upregulated in the Yuanbao chicken...
October 15, 2016: Journal of Molecular Cell Biology
Nikolaos Voulvoulis, Karl Dominic Arpon, Theodoros Giakoumis
The Water Framework Directive 2000/60/EC (WFD) is widely accepted as the most substantial and ambitious piece of European environmental legislation to date. It has been referred to as a once in a generation opportunity to restore Europe's waters and a potential template for future environmental regulations. However, fifteen years since it was adopted, and with many problems and delays in its implementation, the WFD has not delivered its main objectives of non-deterioration of water status and the achievement of good status for all EU waters...
October 13, 2016: Science of the Total Environment
Kyoji Tsuchikama, Zhiqiang An
The antibody-drug conjugate (ADC), a humanized or human monoclonal antibody conjugated with highly cytotoxic small molecules (payloads) through chemical linkers, is a novel therapeutic format and has great potential to make a paradigm shift in cancer chemotherapy. This new antibody-based molecular platform enables selective delivery of a potent cytotoxic payload to target cancer cells, resulting in improved efficacy, reduced systemic toxicity, and preferable pharmacokinetics (PK)/pharmacodynamics (PD) and biodistribution compared to traditional chemotherapy...
October 14, 2016: Protein & Cell
Francesco Gaetano Casino, Carlo Basile
BACKGROUND: The recent interest in incremental haemodialysis (HD) is hindered by the current prescription based on a fixed target model (FTM) for the total (dialytic + renal) equivalent continuous clearance (ECC). The latter is expressed either as standard Kt/V (stdKt/V), i.e. the pre-dialysis averaged concentration of urea-based ECC, or EKRc, i.e. the time averaged concentration-based ECC, corrected for volume (V) = 40 L. Accordingly, there are two different targets: stdKt/V = 2.3 volumes per week (v/wk) and EKRc = 13 mL/min/40 L...
October 14, 2016: Nephrology, Dialysis, Transplantation
Ivana Jochmanova, Karel Pacak
Dysregulated metabolism is one of the key characteristics of cancer cells. The most prominent alterations are present during regulation of cell respiration, which leads to a switch from oxidative phosphorylation to aerobic glycolysis. This metabolic shift results in activation of numerous signaling and metabolic pathways supporting cell proliferation and survival. Recent progress in genetics and metabolomics has allowed us to take a closer look at the metabolic changes present in pheochromocytomas (PHEO) and paragangliomas (PGL)...
October 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Jang-Il Sohn, Jin-Wu Nam
As the advent of next-generation sequencing (NGS) technology, various de novo assembly algorithms based on the de Bruijn graph have been developed to construct chromosome-level sequences. However, numerous technical or computational challenges in de novo assembly still remain, although many bright ideas and heuristics have been suggested to tackle the challenges in both experimental and computational settings. In this review, we categorize de novo assemblers on the basis of the type of de Bruijn graphs (Hamiltonian and Eulerian) and discuss the challenges of de novo assembly for short NGS reads regarding computational complexity and assembly ambiguity...
October 14, 2016: Briefings in Bioinformatics
Salvador Iborra, María Martínez-López, Francisco J Cueto, Ruth Conde-Garrosa, Carlos Del Fresno, Helena M Izquierdo, Clare L Abram, Daiki Mori, Yolanda Campos-Martín, Rosa María Reguera, Benjamin Kemp, Sho Yamasaki, Matthew J Robinson, Manuel Soto, Clifford A Lowell, David Sancho
C-type lectin receptors sense a diversity of endogenous and exogenous ligands that may trigger differential responses. Here, we have found that human and mouse Mincle bind to a ligand released by Leishmania, a eukaryote parasite that evades an effective immune response. Mincle-deficient mice had milder dermal pathology and a tenth of the parasite burden compared to wild-type mice after Leishmania major intradermal ear infection. Mincle deficiency enhanced adaptive immunity against the parasite, correlating with increased activation, migration, and priming by Mincle-deficient dendritic cells (DCs)...
October 5, 2016: Immunity
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