2,453 research outputs found

    Antithrombotic treatment for secondary prevention of stroke and other thromboembolic events in patients with stroke or transient ischemic attack and non-valvular atrial fibrillation : A European Stroke Organisation guideline

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    Patients with ischemic stroke or transient ischemic attack and non-valvular atrial fibrillation have a high risk of recurrent stroke and other vascular events. The aim of this guideline is to provide recommendations on antithrombotic medication for secondary prevention of stroke and other vascular outcomes in these patients. The working group identified questions and outcomes, graded evidence, and developed recommendations according to the Grading of Recommendations Assessment, Development, and Evaluation approach and the European Stroke Organisation (ESO) standard operating procedure for guidelines. The guideline was reviewed and approved by the ESO guideline board and the ESO executive committee. In patients with atrial fibrillation and previous stroke or transient ischemic attack, oral anticoagulants reduce the risk of recurrence over antiplatelets or no antithrombotic treatment. Non-vitamin K antagonist oral anticoagulants are preferred over vitamin K antagonists because they have a lower risk of major bleeding and death. Recommendations are weak regarding timing of treatment, (re-)starting oral anticoagulants in patients with previous intracerebral haemorrhage, and treatment in specific patient subgroups of those of older age, with cognitive impairment, renal failure or small vessel disease, because of a lack of strong evidence. In conclusion, for patients with atrial fibrillation and ischemic stroke or transient ischemic attack, non-vitamin K antagonist oral anticoagulants are the preferred treatment for secondary prevention of recurrent stroke or thromboembolism. Further research is required to determine the best timing for initiating oral anticoagulants after an acute ischemic stroke, whether or not oral anticoagulants should be (re)started in patients with a history of intracerebral haemorrhage, and the best secondary preventive treatment in specific subgroups.Peer reviewe

    Renormalization of Crumpled Manifolds

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    We consider a model of D-dimensional tethered manifold interacting by excluded volume in R^d with a single point. By use of intrinsic distance geometry, we first provide a rigorous definition of the analytic continuation of its perturbative expansion for arbitrary D, 0 < D < 2. We then construct explicitly a renormalization operation, ensuring renormalizability to all orders. This is the first example of mathematical construction and renormalization for an interacting extended object with continuous internal dimension, encompassing field theory.Comment: 10 pages (1 figure, included), harvmac, SPhT/92-15

    The antifungal plant defensin AhPDF1.1b is a beneficial factor involved in adaptive response to zinc overload when it is expressed in yeast cells

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    Antimicrobial peptides represent an expanding family of peptides involved in innate immunity of many living organisms. They show an amazing diversity in their sequence, structure, and mechanism of action. Among them, plant defensins are renowned for their antifungal activity but various side activities have also been described. Usually, a new biological role is reported along with the discovery of a new defensin and it is thus not clear if this multifunctionality exists at the family level or at the peptide level. We previously showed that the plant defensin AhPDF1.1b exhibits an unexpected role by conferring zinc tolerance to yeast and plant cells. In this paper, we further explored this activity using different yeast genetic backgrounds: especially the zrc1 mutant and an UPRE-GFP reporter yeast strain. We showed that AhPDF1.1b interferes with adaptive cell response in the endoplasmic reticulum to confer cellular zinc tolerance. We thus highlighted that, depending on its cellular localization, AhPDF1.1b exerts quite separate activities: when it is applied exogenously, it is a toxin against fungal and also root cells, but when it is expressed in yeast cells, it is a peptide that modulates the cellular adaptive response to zinc overload

    Laminin α4 contributes to airway remodeling and inflammation in asthma

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    Airway inflammation and remodeling are characteristic features of asthma, both contributing to airway hyperresponsiveness (AHR) and lung function limitation. Airway smooth muscle (ASM) accumulation and extracellular matrix deposition are characteristic features of airway remodeling, which may contribute to persistent AHR. Laminins containing the α2 chain contribute to characteristics of ASM remodeling in vitro and AHR in animal models of asthma. The role of other laminin chains, including the laminin α4 and α5 chains, which contribute to leukocyte migration in other diseases, is currently unknown. The aim of the current study was to investigate the role of these laminin chains in ASM function and in AHR, remodeling and inflammation in asthma. Expression of both laminin α4 and α5 was observed in the human and mouse ASM bundle. In vitro, laminin α4 was found to promote a pro-proliferative, pro-contractile and pro-fibrotic ASM cell phenotype. In line, treatment with laminin α4 and α5 function-blocking antibodies reduced allergen-induced increases in ASM mass in a mouse model of allergen-induced asthma. Moreover, eosinophilic inflammation was reduced by the laminin α4 function-blocking antibody as well. Using airway biopsies from healthy subjects and asthmatic patients, we found inverse correlations between ASM α4 chain expression and lung function and AHR, whereas eosinophil numbers correlated positively with expression of laminin α4 in the ASM bundle. This study for the first time indicates a prominent role for laminin α4 in ASM function and in inflammation, AHR and remodeling in asthma, whereas the role of laminin α5 is more subtle

    Adiabatic limit and the slow motion of vortices in a Chern-Simons-Schr\"odinger system

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    We study a nonlinear system of partial differential equations in which a complex field (the Higgs field) evolves according to a nonlinear Schroedinger equation, coupled to an electromagnetic field whose time evolution is determined by a Chern-Simons term in the action. In two space dimensions, the Chern-Simons dynamics is a Galileo invariant evolution for A, which is an interesting alternative to the Lorentz invariant Maxwell evolution, and is finding increasing numbers of applications in two dimensional condensed matter field theory. The system we study, introduced by Manton, is a special case (for constant external magnetic field, and a point interaction) of the effective field theory of Zhang, Hansson and Kivelson arising in studies of the fractional quantum Hall effect. From the mathematical perspective the system is a natural gauge invariant generalization of the nonlinear Schroedinger equation, which is also Galileo invariant and admits a self-dual structure with a resulting large space of topological solitons (the moduli space of self-dual Ginzburg-Landau vortices). We prove a theorem describing the adiabatic approximation of this system by a Hamiltonian system on the moduli space. The approximation holds for values of the Higgs self-coupling constant close to the self-dual (Bogomolny) value of 1. The viability of the approximation scheme depends upon the fact that self-dual vortices form a symplectic submanifold of the phase space (modulo gauge invariance). The theorem provides a rigorous description of slow vortex dynamics in the near self-dual limit.Comment: Minor typos corrected, one reference added and DOI give

    Genetic regulation of gene expression of MIF family members in lung tissue

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    Macrophage migration inhibitory factor (MIF) is a cytokine found to be associated with chronic obstructive pulmonary disease (COPD). However, there is no consensus on how MIF levels differ in COPD compared to control conditions and there are no reports on MIF expression in lung tissue. Here we studied gene expression of members of the MIF family MIF, D-Dopachrome Tautomerase (DDT) and DDT-like (DDTL) in a lung tissue dataset with 1087 subjects and identified single nucleotide polymorphisms (SNPs) regulating their gene expression. We found higher MIF and DDT expression in COPD patients compared to non-COPD subjects and found 71 SNPs significantly influencing gene expression of MIF and DDTL. Furthermore, the platform used to measure MIF (microarray or RNAseq) was found to influence the splice variants detected and subsequently the direction of the SNP effects on MIF expression. Among the SNPs found to regulate MIF expression, the major LD block identified was linked to rs5844572, a SNP previously found to be associated with lower diffusion capacity in COPD. This suggests that MIF may be contributing to the pathogenesis of COPD, as SNPs that influence MIF expression are also associated with symptoms of COPD. Our study shows that MIF levels are affected not only by disease but also by genetic diversity (i.e. SNPs). Since none of our significant eSNPs for MIF or DDTL have been described in GWAS for COPD or lung function, MIF expression in COPD patients is more likely a consequence of disease-related factors rather than a cause of the disease
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