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101.
Stephane Fournier Patrick Taffé Dragana Radovanovic Erik Von Elm Beata Morawiec Jean-Christophe Stauffer Paul Erne Ahmed Beggah Pierre Monney Patrizio Pascale Juan-Fernando Iglesias Eric Eeckhout Olivier Muller 《PloS one》2015,10(3)
Background
Different studies have shown circadian variation of ischemic burden among patients with ST-Elevation Myocardial Infarction (STEMI), but with controversial results. The aim of this study was to analyze circadian variation of myocardial infarction size and in-hospital mortality in a large multicenter registry.Methods
This retrospective, registry-based study was based on data from AMIS Plus, a large multicenter Swiss registry of patients who suffered myocardial infarction between 1999 and 2013. Peak creatine kinase (CK) was used as a proxy measure for myocardial infarction size. Associations between peak CK, in-hospital mortality, and the time of day at symptom onset were modelled using polynomial-harmonic regression methods.Results
6,223 STEMI patients were admitted to 82 acute-care hospitals in Switzerland and treated with primary angioplasty within six hours of symptom onset. Only the 24-hour harmonic was significantly associated with peak CK (p = 0.0001). The maximum average peak CK value (2,315 U/L) was for patients with symptom onset at 23:00, whereas the minimum average (2,017 U/L) was for onset at 11:00. The amplitude of variation was 298 U/L. In addition, no correlation was observed between ischemic time and circadian peak CK variation. Of the 6,223 patients, 223 (3.58%) died during index hospitalization. Remarkably, only the 24-hour harmonic was significantly associated with in-hospital mortality. The risk of death from STEMI was highest for patients with symptom onset at 00:00 and lowest for those with onset at 12:00.Discussion
As a part of this first large study of STEMI patients treated with primary angioplasty in Swiss hospitals, investigations confirmed a circadian pattern to both peak CK and in-hospital mortality which were independent of total ischemic time. Accordingly, this study proposes that symptom onset time be incorporated as a prognosis factor in patients with myocardial infarction. 相似文献102.
Raimon Sabate Frederic Rousseau Joost Schymkowitz Salvador Ventura 《PLoS computational biology》2015,11(1)
Typical amyloid diseases such as Alzheimer''s and Parkinson''s were thought to exclusively result from de novo aggregation, but recently it was shown that amyloids formed in one cell can cross-seed aggregation in other cells, following a prion-like mechanism. Despite the large experimental effort devoted to understanding the phenomenon of prion transmissibility, it is still poorly understood how this property is encoded in the primary sequence. In many cases, prion structural conversion is driven by the presence of relatively large glutamine/asparagine (Q/N) enriched segments. Several studies suggest that it is the amino acid composition of these regions rather than their specific sequence that accounts for their priogenicity. However, our analysis indicates that it is instead the presence and potency of specific short amyloid-prone sequences that occur within intrinsically disordered Q/N-rich regions that determine their prion behaviour, modulated by the structural and compositional context. This provides a basis for the accurate identification and evaluation of prion candidate sequences in proteomes in the context of a unified framework for amyloid formation and prion propagation. 相似文献
103.
104.
Protease‐activated receptor (PAR)‐2 is required for PAR‐1 signalling in pulmonary fibrosis
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Cong Lin Jan von der Thüsen Joost Daalhuisen Marieke ten Brink Bruno Crestani Tom van der Poll C. Arnold Spek 《Journal of cellular and molecular medicine》2015,19(6):1346-1356
Idiopathic pulmonary fibrosis is the most devastating diffuse fibrosing lung disease of unknown aetiology. Compelling evidence suggests that both protease‐activated receptor (PAR)‐1 and PAR‐2 participate in the development of pulmonary fibrosis. Previous studies have shown that bleomycin‐induced lung fibrosis is diminished in both PAR‐1 and PAR‐2 deficient mice. We thus have been suggested that combined inactivation of PAR‐1 and PAR‐2 would be more effective in blocking pulmonary fibrosis. Human and murine fibroblasts were stimulated with PAR‐1 and PAR‐2 agonists in the absence or presence of specific PAR‐1 or PAR‐2 antagonists after which fibrotic markers like collagen and smooth muscle actin were analysed by Western blot. Pulmonary fibrosis was induced by intranasal instillation of bleomycin into wild‐type and PAR‐2 deficient mice with or without a specific PAR‐1 antagonist (P1pal‐12). Fibrosis was assessed by hydroxyproline quantification and (immuno)histochemical analysis. We show that specific PAR‐1 and/or PAR‐2 activating proteases induce fibroblast migration, differentiation and extracellular matrix production. Interestingly, however, combined activation of PAR‐1 and PAR‐2 did not show any additive effects on these pro‐fibrotic responses. Strikingly, PAR‐2 deficiency as well as pharmacological PAR‐1 inhibition reduced bleomycin‐induced pulmonary fibrosis to a similar extent. PAR‐1 inhibition in PAR‐2 deficient mice did not further diminish bleomycin‐induced pulmonary fibrosis. Finally, we show that the PAR‐1‐dependent pro‐fibrotic responses are inhibited by the PAR‐2 specific antagonist. Targeting PAR‐1 and PAR‐2 simultaneously is not superior to targeting either receptor alone in bleomycin‐induced pulmonary fibrosis. We postulate that the pro‐fibrotic effects of PAR‐1 require the presence of PAR‐2. 相似文献
105.
Gera A. de Haan Bart J. M. Melis-Dankers Wiebo H. Brouwer Oliver Tucha Joost Heutink 《PloS one》2015,10(8)
IntroductionHomonymous visual field defects (HVFD) are a common consequence of postchiasmatic acquired brain injury and often lead to mobility-related difficulties. Different types of compensatory scanning training have been developed, aimed at decreasing consequences of the HVFD by changing visual scanning.AimThe aim of the present study is to examine the effects of a compensatory scanning training program using horizontal scanning on mobility-related activities and participation in daily life.MethodThe main interest of this study is to assess the effectiveness of training on mobility-related activities and participation in daily life. Visual scanning tests, such as dot counting and visual search, and control measures for visual functions and reading have been included as well. First, it is examined how performance on scanning and mobility-related measures is affected in patients with HVFD by comparing scores with scores of a healthy control group (n = 25). Second, the effect of training is assessed using an RCT design, in which performance of 26 patients before and after training is compared to performance of 23 patients in a waiting list control group.ResultsSelf-reported improvements after training were found, accompanied by improvements in detecting peripheral stimuli and avoiding obstacles during walking, especially in dual task situations in which a second task limits the attentional capacity available for compensatory scanning. Training only improved mobility-related activities in which detection of peripheral stimuli is important, while no improvement was found on tests that require other visual skills, such as reading, visual counting and visual search.ConclusionThis is the first RCT to evaluate the effects of a compensatory scanning training that is based on a systematic horizontal scanning rhythm. This training improved mobility-related activities. The results suggest that different types of compensatory scanning strategies are appropriate for different types of activities.
Trial Registration
ISRCTN Registry ISRCTN16833414 相似文献106.
107.
Ralph E. Schmidt Stephane Cullati Elizabeth Mostofsky Guy Haller Thomas Agoritsas Murray A. Mittleman Thomas V. Perneger Delphine S. Courvoisier 《PloS one》2015,10(10)
To examine the association between healthcare-related regrets and sleep difficulties among nurses and physicians, we surveyed 240 nurses and 220 physicians at the University Hospitals of Geneva. Regret intensity and regret coping were measured using validated scales. Sleep difficulties were measured using the Insomnia Severity Index (ISI), and an additional question assessed the frequency of sleeping pill use. After controlling for sex, profession, years of experience, rate of employment, and depression as well as for all other regret-related variables, the following variables remained significantly associated with self-rated severity of insomnia: regret intensity (slope = 1.32, p = 0.007, 95%CI: [0.36; 2.29], std. coefficient = 0.16) and maladaptive (e.g., rumination) emotion-focused coping (slope = 1.57, p = 0.002, 95%CI: [0.60; 2.55], std. coefficient = 0.17) remained significant predictors of self-rated insomnia severity. If these cross-sectional associations represent causal effects, the development of regret-management programs may represent a promising approach to mitigating sleep difficulties of healthcare professionals. 相似文献
108.
In habitats recently colonized by cyclical parthenogens, founder events lead to genetic differences between populations that do not erode quickly despite ongoing dispersal. By comparing the genetic composition during initial colonization with that of the diapausing egg bank at a local scale, we here present the relative contribution of the founding clones to the build-up of genetic diversity and differentiation of a newly established cladoceran population. We monitored the population genetic structure of Daphnia magna in one newly created pond as well as the diapausing egg banks of four water bodies in the neighbouring area. Our population was founded by four individuals. After the first growing season, the largest contribution to the sexually produced resting egg bank came from only two clones. Descendants of initially rare clones and potentially also additional immigrant clones profited from outbreeding vigour and increased their frequency during the first few years after colonization. Beyond this, no further significant changes in genetic structure were observed in the egg bank. At this point, priority effects became fully operational and led to sustained population genetic differentiation from nearby ponds. Our results support that colonization dynamics strongly influence within and among population genetic variation and evolutionary potential of populations. 相似文献
109.
110.
Robert W. Schwenk Graham P. Holloway Joost J.F.P. Luiken Arend Bonen Jan F.C. Glatz 《Prostaglandins, leukotrienes, and essential fatty acids》2010,82(4-6):149-154
Transport of long-chain fatty acids across the cell membrane has long been thought to occur by passive diffusion. However, in recent years there has been a fundamental shift in understanding, and it is now generally recognized that fatty acids cross the cell membrane via a protein-mediated mechanism. Membrane-associated fatty acid-binding proteins (‘fatty acid transporters’) not only facilitate but also regulate cellular fatty acid uptake, for instance through their inducible rapid (and reversible) translocation from intracellular storage pools to the cell membrane. A number of fatty acid transporters have been identified, including CD36, plasma membrane-associated fatty acid-binding protein (FABPpm), and a family of fatty acid transport proteins (FATP1–6). Fatty acid transporters are also implicated in metabolic disease, such as insulin resistance and type-2 diabetes. In this report we briefly review current understanding of the mechanism of transmembrane fatty acid transport, and the function of fatty acid transporters in healthy cardiac and skeletal muscle, and in insulin resistance/type-2 diabetes. Fatty acid transporters hold promise as a future target to rectify lipid fluxes in the body and regain metabolic homeostasis. 相似文献