Does prior antithrombotic therapy influence recurrence and bleeding risk in stroke patients with atrial fibrillation or atrial flutter?

The authors would like to thank the patients of the NNUH Stroke Register cohort and the data team of the Norfolk and Norwich University Stroke Services. NNUH Stroke Register is maintained by the NNUH Stroke Services.Peer reviewedPostprin

Umpolung Reactivity of in Situ Generated Phosphido-Boranes: An Entry to P-Stereogenic Aminophosphine-Boranes

International audienceThe synthesis of P-stereogenic aminophos-phine-boranes has been developed on the basis of umpolung reactivity of in situ generated alkylarylphosphido-boranes, which are normally configurationally unstable intermediates. In our case, their high configurational stability was due to the slow release of the hydroxyalkyl protecting group, together with the fast formation of the iodophosphanylborane in the presence of N-iodosuccinimide. The subsequent substitution reaction was found to proceed in moderate to good yields and in a very high stereospecifity (es) using a variety of amines as nucleophiles

Development of a flexible nanocomposite TiO2 film as a protective coating for bioapplications of superelastic NiTi alloys

International audienceAn experimental procedure to coat superelastic NiTi alloys with flexible TiO2 protective nanocomposite films using sol-gel technology was developed in this work to improve the metal biocompatibility without deteriorating its superelastic mechanical properties. The coatings were characterized by scanning and transmission electron microscopy, X-ray photoelectron spectroscopy, Raman spectroscopy, and glazing incidence X-ray diffraction. The elasticity of the film was tested in coated specimens submitted to three-point bending tests. A short densification by thermal treatment at 500 degrees C for 10 min yielded a bilayer film consisting of a 50 nm-thick crystallized TiO2 at the inner interface with another 50-nm-thick amorphous oxide film at the outer interface. This bilayer could sustain over 6.4% strain without cracking and could thus be used to coat biomedical instruments as well as other devices made with superelastic NiTi alloys. (C) 2016 Elsevier B.V. All rights reserved

Cold acclimation does not alter physiological or perceptual responses during subsequent exercise in the heat

Introduction: Warfighters often train and conduct operations in cold environments. Specifically, military trainees and divers that are repeatedly exposed to cold water may experience inadvertent cold acclimatization, which results in body heat retention. These same warfighters can quickly switch between environments (cold to hot or hot to cold) given the nature of their work. This may present a risk of early onset of hyperthermia when cold-acclimatized warfighters are subsequently exposed to physiological insults that increase body temperature, such as exercise and heat stress. However, there is currently no evidence that suggests this is the case. The purpose of this work, therefore, is to determine what impact, if any, repeated immersion in cold water has on subsequent exercise in the heat. Materials and Methods: Twelve healthy subjects (values in mean +/- SD: age, 25.6 +/- 5.2 years; height, 174.0 +/- 8.9 cm; weight, 75.6 +/- 13.1 kg) voluntarily provided written informed consent in accordance with the San Diego State University Institutional Review Board. They first completed 120 minutes of moderate treadmill walking in 40 degrees C and 40% relative humidity. During this trial, subjects' physiological and perceptual responses were recorded. Twenty-four hours later, subjects began a cold acclimation protocol, which consisted of seven, 90-minute immersions in cold water (10 degrees C, water level to chest). Each immersion was also separated by 24 hours. Subjects then repeated a subsequent trial of exercise in the heat 24 hours after the final immersion of the cold acclimation protocol. Results: Results from cold acclimation revealed no change in core temperature, a decrease in skin temperature, and attenuated shivering and lactate responses, which supports a successful insulative-hypothermic cold acclimation response. This type of cold acclimation response primarily results in heat retention with associated energy conservation. Findings for heat trials (pre-cold acclimation and post-cold acclimation) revealed no differences between trials for all measurements, suggesting that cold acclimation did not influence physiological or perceptual responses during exercise in the heat. Conclusion: Our findings indicate that military divers or trainees that are frequently exposed to cold water, and hence have the ability to experience cold acclimatization, will likely not be at greater risk of increased thermal strain when subsequently exposed to physical activity in hot environments. In this study, no physiological or perceptual differences were observed between trials before and after cold acclimation, suggesting that cold acclimation does not present a greater hyperthermia risk during subsequent exercise in the heat

Slowing down fat digestion and absorption by an oxadiazolone inhibitor targeting selectively gastric lipolysis

International audienceBased on a previous study and in silico molecular docking experiments, we have designed and synthesized a new series of ten 5-Alkoxy-N-3-(3-PhenoxyPhenyl)-1,3,4-Oxadiazol-2(3H)-one derivatives (RmPPOX). These molecules were further evaluated as selective and potent inhibitors of mammalian digestive lipases: purified dog gastric lipase (DGL) and guinea pig pancreatic lipase related protein 2 (GPLRP2), as well as porcine (PPL) and human (HPL) pancreatic lipases contained in porcine pancreatic extracts (PPE) and human pancreatic juices (HPJ), respectively. These compounds were found to strongly discriminate classical pancreatic lipases (poorly inhibited) from gastric lipase (fully inhibited). Among them, the 5-(2-(Benzyloxy)ethoxy)-3-(3-PhenoxyPhenyl)-1,3,4-Oxadiazol-2(3H)-one (BemPPOX) was identified as the most potent inhibitor of DGL, even more active than the FDA-approved drug Orlistat. BemPPOX and Orlistat were further compared in vitro in the course of test meal digestion, and in vivo with a mesenteric lymph duct cannulated rat model to evaluate their respective impacts on fat absorption. While Orlistat inhibited both gastric and duodenal lipolysis and drastically reduced fat absorption in rats, BemPPOX showed a specific action on gastric lipolysis that slowed down the overall lipolysis process and led to a subsequent reduction of around 55% of the intestinal absorption of fatty acids compared to controls. All these data promote BemPPOX as a potent candidate to efficiently regulate the gastrointestinal lipolysis, and to investigate its link with satiety mechanisms and therefore develop new strategies to "fight against obesity"

Umbrella Data Management Plans to integrate FAIR data:Lessons from the ISIDORe and BY-COVID consortia for pandemic preparedness

The Horizon Europe project ISIDORe is dedicated to pandemic preparedness and responsiveness research. It brings together 17 Research Infrastructures (RIs) and networks to provide a broad range of services to infectious disease researchers. An efficient and structured treatment of data is central to ISIDORe’s aim to furnish seamless access to its multidisciplinary catalogue of services, and to ensure that users’ results are treated FAIRly. ISIDORe therefore requires a data management plan (DMP) covering both access management and research outputs, applicable over a broad range of disciplines, and compatible with the constraints and existing practices of its diverse partners. We undertook an iterative, step-by-step, process to build a community-approved living document, identifying good practices and processes, on the basis of use cases, presented as proof of concepts. International fora such as the RDA and EOSC, and primarily the BY-COVID project, furnished registries, tools and online data platforms, as well as standards, and the support of data scientists. Together, these elements provide a path for building an umbrella, FAIR-compliant DMP, aligned as fully as possible with FAIR principles, which could also be applied as a framework for data management harmonisation in other large-scale, challenge-driven projects. Finally, we discuss how data management and reuse can be further improved through the writing of realistic DMPs using 'DMP profiles' and, in the future, the contribution of an inter RIs data steward network, to produce a Community of Practice that could be integrated into planned trans-RI competence centres.Preprint added on zenodo with the autorisation of DSJ Edito