Atrial Fibrillation and Risk of Dementia: Epidemiology, Mechanisms, and Effect of Anticoagulation

Atrial fibrillation (AF) is one of the cardiovascular risk factors for dementia. Several longitudinal studies have reported an association between AF and dementia independently of stroke history. Although the mechanisms underlying this association are not fully understood, proposed mechanisms include cerebral hypoperfusion, inflammation, genetic factors, cerebral microbleeds, and recurrent silent cerebral ischemia. Oral anticoagulation can be used to minimize risk of cognitive decline and dementia, given that brain insults can be caused by chronic microemboli or microbleeds. However, controversy on the effects of warfarin and direct oral anticoagulants on this risk exists. This article will address these aspects, with data on the studies already published and a critical view on this subject

Unveiling the "Three Finger Pharmacophore" required for p53-MDM2 Inhibition by Saturation Transfer Difference NMR Initial Growth Rates Approach

Inhibitors of the p53-MDM2 protein-protein interaction are emerging as a novel and validated approach to treating cancer. In this work we describe the synthesis and inhibitory evaluation of a series of isoquinolin-1-one analogues, and highlight the utility of an initial growth rates STD NMR approach supported by protein-ligand docking to investigate p53-MDM2 inhibition. The approach is illustrated by the study of compound 1, providing key insights into the binding mode of this kind of MDM2 ligands and, more importantly, readily unveiling the previously proposed three finger pharmacophore requirement for p53-MDM2 inhibition

Structure-Property Optimization of a Series of Imidazopyridines for Visceral Leishmaniasis

Leishmaniasis is a collection of diseases caused by more than 20 Leishmania parasite species that manifest as either visceral, cutaneous, or mucocutaneous leishmaniasis. Despite the significant mortality and morbidity associated with leishmaniasis, it remains a neglected tropical disease. Existing treatments have variable efficacy, significant toxicity, rising resistance, and limited oral bioavailability, which necessitates the development of novel and affordable therapeutics. Here, we report on the continued optimization of a series of imidazopyridines for visceral leishmaniasis and a scaffold hop to a series of substituted 2-(pyridin-2-yl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazoles with improved absorption, distribution, metabolism, and elimination properties

A novel cardiovascular magnetic resonance risk score for predicting mortality following surgical aortic valve replacement

The increasing prevalence of patients with aortic stenosis worldwide highlights a clinical need for improved and accurate prediction of clinical outcomes following surgery. We investigated patient demographic and cardiovascular magnetic resonance (CMR) characteristics to formulate a dedicated risk score estimating long-term survival following surgery. We recruited consecutive patients undergoing CMR with gadolinium administration prior to surgical aortic valve replacement from 2003 to 2016 in two UK centres. The outcome was overall mortality. A total of 250 patients were included (68 ± 12 years, male 185 (60%), with pre-operative mean aortic valve area 0.93 ± 0.32cm2, LVEF 62 ± 17%) and followed for 6.0 ± 3.3 years. Sixty-one deaths occurred, with 10-year mortality of 23.6%. Multivariable analysis showed that increasing age (HR 1.04, P = 0.005), use of antiplatelet therapy (HR 0.54, P = 0.027), presence of infarction or midwall late gadolinium enhancement (HR 1.52 and HR 2.14 respectively, combined P = 0.12), higher indexed left ventricular stroke volume (HR 0.98, P = 0.043) and higher left atrial ejection fraction (HR 0.98, P = 0.083) associated with mortality and developed a risk score with good discrimination. This is the first dedicated risk prediction score for patients with aortic stenosis undergoing surgical aortic valve replacement providing an individualised estimate for overall mortality. This model can help clinicians individualising medical and surgical care

Efeitos da inclusão de blend de prebióticos na microbiologia cecal e peso de órgãos de leitões recém-desmamados

O objetivo do experimento foi avaliar os efeitos da inclusão de mananoligossacarídeo (MOS), β-glucano, frutoligossacarídeo (FOS) e galactoligossacarídeo (GOS) em dietas de leitões em fase de creche, com idade média de 21 dias, sobre o peso relativo dos órgãos (estômago, fígado, intestinos e baço) e microbiologia do conteúdo do ceco dos animais. O experimento teve duração de 14 dias e foram utilizados 40 leitões recém-desmamados, distribuídos em um delineamento em blocos ao acaso com 5 tratamentos (T): T1 = dieta basal com inclusão de antibiótico promotor de crescimento (120 ppm de halquinol); T2 = dieta basal com adição de MOS e β-glucano (3,0 kg/t); T3 = dieta basal com adição de MOS e β-glucano (2,0kg/t) + GOS e FOS (1,0kg/t) (1:9); T4 = dieta basal com adição de MOS e β-glucano (2,0kg/t) + GOS e FOS (1,0kg/t) (3:7); T5 = dieta basal com adição de MOS e β-glucano (2,0kg/t) + GOS e FOS (1,0kg/t) (5:5), com oito repetições, sendo cada animal uma unidade experimentalFil: Viana, Yasmim Silva. Universidad Estadual Paulista "Júlio de Mesquita Filho" (Brasil)Fil: Alvarenga, Patrícia Versuti Arantes. Universidad Estadual Paulista "Júlio de Mesquita Filho" (Brasil)Fil: Tse, Marcos Lívio Panhoza. Universidad Estadual Paulista "Júlio de Mesquita Filho" (Brasil)Fil: Paula, Vinícius Ricardo Cambito de. Universidad Estadual Paulista "Júlio de Mesquita Filho" (Brasil)Fil: Ferreira, Silvia Letícia. Universidad Estadual Paulista "Júlio de Mesquita Filho" (Brasil)Fil: Berto, Dirlei Antonio. Universidad Estadual Paulista "Júlio de Mesquita Filho" (Brasil

Near real-time vaccine safety surveillance using electronic health records-a systematic review of the application of statistical methods.

PURPOSE: Pre-licensure studies have limited ability to detect rare adverse events (AEs) to vaccines, requiring timely post-licensure studies. With the increasing availability of electronic health records (EHR) near real-time vaccine safety surveillance using these data has emerged as an option. We reviewed methods currently used to inform development of similar systems for countries considering their introduction. METHODS: Medline, EMBASE and Web of Science were searched, with additional searches of conference abstract books. Questionnaires were sent to organizations worldwide to ascertain unpublished studies. Eligible studies used EHR and regularly assessed pre-specified AE to vaccine(s). Key features of studies were compared descriptively. RESULTS: From 2779 studies, 31 were included from the USA (23), UK (6), and Taiwan and New Zealand (1 each). These were published/conducted between May 2005 and April 2015. Thirty-eight different vaccines were studied, focusing mainly on influenza (47.4%), especially 2009 H1N1 vaccines. Forty-six analytic approaches were used, reflecting frequency of EHR updates and the AE studied. Poisson-based maximized sequential probability ratio test was the most common (43.5%), followed by its binomial (23.9%) and conditional versions (10.9%). Thirty-seven of 49 analyses (75.5%) mentioned control for confounding, using an adjusted expected rate (51.4% of those adjusting), stratification (16.2%) or a combination of a self-controlled design and stratification (13.5%). Guillain-Barré syndrome (11.9%), meningitis/encephalitis/myelitis (11.9%) and seizures (10.8%) were studied most often. CONCLUSIONS: Near real-time vaccine safety surveillance using EHR has developed over the past decade but is not yet widely used. As more countries have access to EHR, it will be important that appropriate methods are selected, considering the data available and AE of interest

OCCURRENCE OF Escherichia coli O157:H7 IN MEAT PRODUCTS AND SENSIBILITY OF THE DETECTION METHODS

The occurrence of E.coli O157:H7 was evaluated in 340 samples of meat products and industrial environment of meat manufacturers from the South and Southeast regions of Brazil, from April, 1998 to April, 1999. Pathogen was not detected in any of the samples analysed, and the evaluation of the sensibility of the studied detection methods showed that both, culture and immuno-assay methods detected E.coli O157:H7 in pure culture in initial population levels of 0.5Log CFU/mL of enrichment broth.Foi verificada a ocorrência de Escherichia coli O157:H7 em 340 amostras de produtos cárneos e ambiente industrial, provenientes de frigoríficos do Sul e Sudeste do Brasil, no período de abril/98 a abril/99. A presença de E.coli O157:H7 não foi detectada em nenhuma das amostras analisadas e os resultados da avaliação da sensibilidade dos métodos de detecção evidenciaram que tanto o método cultural quanto o imunoensaio da Neogem foram capazes de detectar a presença de E.coli O157:H7 em cultura pura em concentrações iniciais de menos de 0,5Log UFC/mL do caldo de enriquecimento.22322

Spin dynamics in semiconductors

This article reviews the current status of spin dynamics in semiconductors which has achieved a lot of progress in the past years due to the fast growing field of semiconductor spintronics. The primary focus is the theoretical and experimental developments of spin relaxation and dephasing in both spin precession in time domain and spin diffusion and transport in spacial domain. A fully microscopic many-body investigation on spin dynamics based on the kinetic spin Bloch equation approach is reviewed comprehensively.Comment: a review article with 193 pages and 1103 references. To be published in Physics Reports