Composition of the Intestinal Microbiota Determines the Outcome of Virus-Triggered Colitis in Mice

The intestinal microbiota is a complex ecosystem implicated in host health and disease. Inflammatory bowel disease (IBD) is a multifactorial chronic disorder of the gastrointestinal mucosa. Even though the exact mechanisms are still unknown, the intestinal microbiota is crucial in IBD development. We previously showed that murine norovirus (MNV) induces colitis in the Il10-deficient (Il10(-/-)) mouse model of IBD in a microbiota-dependent manner. Thus, in this study we analyzed whether distinct minimal bacterial consortia influence the outcome of MNV-triggered colitis in Il10(-/-) mice. Gnotobiotic Il10(-/-) mice associated with Oligo-Mouse-Microbiota 12 (OMM12) or Altered Schaedler Flora (ASF) developed little to no inflammatory lesions in the colon and cecum. MNV infection exacerbated colitis severity only in ASF-colonized mice, but not in those associated with OMM12. Four weeks after MNV infection, inflammatory lesions in ASF-colonized Il10(-/-) mice were characterized by epithelial hyperplasia, infiltration of inflammatory cells, and increased barrier permeability. Co-colonization of ASF-colonized Il10(-/-) mice with segmented filamentous bacteria (SFB) abolished MNV-induced colitis, whereas histopathological scores in SFB-OMM12-co-colonized mice stayed unchanged. Moreover, SFB only colonized mice associated with ASF. The SFB-mediated protective effects in ASF-colonized mice involved enhanced activation of intestinal barrier defense mechanisms and mucosal immune responses in the chronic and acute phase of MNV infection. SFB colonization strengthened intestinal barrier function by increasing expression of tight junction proteins, antimicrobial peptides and mucus. Furthermore, SFB colonization enhanced the expression of pro-inflammatory cytokines such as Tnf alpha, Il1 beta, and Il12 alpha, as well as the expression of the regulatory cytokine Tgf beta. Altogether, our results showed that MNV-triggered colitis depends on the microbial context

Boundary condition enforcement for renormalised weakly compressible meshless Lagrangian methods

This paper introduces a boundary condition scheme for weakly compressible (WC) renormalised first-order accurate meshless Lagrangian methods (MLM) by considering both solid and free surface conditions. A hybrid meshless Lagrangian method-finite difference (MLM-FD) scheme on prescribed boundary nodes is proposed to enforce Neumann boundary conditions. This is used to enforce symmetry boundary conditions and the implied Neumann pressure boundary conditions on solid boundaries in a manner consistent with the Navier-Stokes equation leading to the accurate recovery of surface pressures. The free surface boundary conditions allow all differential operators to be approximated by the same renormalised scheme while also efficiently determining free surface particles. The boundary conditions schemes are implemented for two renormalised MLMs. A WC smoothed particle hydrodynamics (SPH) solver is compared to a WC generalised finite difference (GFD) solver. Applications in both 2D and 3D are explored. A substantial performance benefit was found when comparing the WCGFD solver to the WCSPH solver with the WCGFD solver realising a maximum speedup in the range of three times over WCSPH in both 2D and 3D configurations. The solvers were implemented in C++ and used the NVIDIA CUDA 10.1 toolkit for the parallelisation of the solvers.http://www.elsevier.com/locate/enganaboundhj2022Mechanical and Aeronautical Engineerin

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Empowerment of Whom and for What? Financial Literacy Education and the New Regulation of Consumer Financial Services

Financial regulators in many states recently have obtained statuory mandates to enhance consumer financial literacy. This paper investicages the development of policy pursuant to such mandates in the UK and Canada to identify how national regulators in both countries represent financial market place. It finds that regulators in both countries represent financial education as empowerment and responsible consumer behaviour. The paper rekates the tension between empowerment and responsibilization aspects of literacy enhancement to policy goals of expectations of protection. It raises questions about regulators' use of consumer education to responsiblize consumption of financial products and calls for further research on the international growth of financial literacy education as a regulatory project