Atualização da diretriz brasileira de insuficiência cardíaca crônica - 2012

Esta atualização da Diretriz de Insuficiência Cardíaca Crônica (IC) - 2012 surge para reavaliar as recomendações através de uma avaliação criteriosa das pesquisas (considerando-se a qualidade dos estudos), fundamental para que se atinja esse propósito. Para tanto, foi dada ênfase ao efeito em desfechos de morte, à qualidade "CONSORT" (Consolidated Standards of Reporting Trials), à descrição qualitativa e quantitativa da otimização da medicação, à população realmente incluída, às metanálises somente de estudos qualidade "CONSORT", à custo-efetividade, à existência de efeito de classe, ao número de pacientes incluídos e à análise de subgrupos apenas para gerar hipóteses. Na área da epidemiologia, as recentes abordagens das características da IC com fração de ejeção preservada (ICFEP) e da importância da IC como causa de morte no Brasil foram revisadas. Além disso, este documento contempla a reavaliação do valor dos biomarcadores no diagnóstico e no seguimento da IC, o papel diagnóstico da angiotomografia coronariana nos casos de risco intermediário ou baixo risco de doença coronariana, a não recomendação de rotina do telemonitoramento; o surgimento da avaliação familiar como recomendação importante, e a reavaliação da restrição da adição de sal na dieta. As clínicas de IC e reabilitação física, apesar de alguns resultados negativos ou controversos quanto à mortalidade, continuam com recomendação importante. No campo do tratamento farmacológico, abrange-se a reavaliação da indicação do nebivolol, introduz-se a ivabradina como um novo paradigma no tratamento, os antagonistas da aldosterona não têm efeito de classe reconhecido, o ômega 3 passa a ser recomendado, o ferro administrado por via endovenosa e o sildenafil recebem indicação em casos selecionados. Todas as recomendações para outras etiologias são expandidas para a Doença de Chagas. Na área da anticoagulação, recomenda-se a utilização dos escores CHA2DS2VASC e o HAS-BLED na fibrilação atrial, com introdução de inibidores da trombina e do fator Xa como alternativas na anticoagulação. No tratamento cirúrgico da IC, considerou-se que resultados neutros do estudo STICH influenciaram as recomendações, o transplante cardíaco continua a ser o tratamento indicado nas fases evolutivas tardias de IC, os dispositivos de assistência circulatória mecânica para terapia de destino passam a ter recomendação, a duração do QRS foi fundamental na indicação de TRV-AV, e o CDI continua com recomendação I para miocardiopatia isquêmica. Entretanto, baseada em análise crítica dos estudos considerando-se o custo-efetividade, o CDI não atingiu recomendação I para classes menos graves devido as limitações dos estudos. Também a importância da cardiotoxicidade por drogas para tratamento de neoplasias foi ressaltada, o tratamento da IC na gravidez e da miocardite foi revisado. Novos potenciais métodos de tratamento em fase de pesquisa são apresentados e novos fluxogramas de diagnóstico e tratamento da IC, reformulados, foram incluído

CoRoT-22 b: a validated 4.9 RE exoplanet in 10-day orbit

The CoRoT satellite has provided high-precision photometric light curves for more than 163,000 stars and found several hundreds of transiting systems compatible with a planetary scenario. If ground-based velocimetric observations are the best way to identify the actual planets among many possible configurations of eclipsing binary systems, recent transit surveys have shown that it is not always within reach of the radial-velocity detection limits. In this paper, we present a transiting exoplanet candidate discovered by CoRoT whose nature cannot be established from ground-based observations, and where extensive analyses are used to validate the planet scenario. They are based on observing constraints from radial-velocity spectroscopy, adaptive optics imaging and the CoRoT transit shape, as well as from priors on stellar populations, planet and multiple stellar systems frequency. We use the fully Bayesian approach developed in the PASTIS analysis software, and conclude that the planet scenario is at least 1400 times more probable than any other false positive scenario. The primary star is a metallic solar-like dwarf, with Ms = 1.099+-0.049 Msun and Rs = 1.136 (+0.038,-0.090) Rsun . The validated planet has a radius of Rp = 4.88 (+0.17,-0.39) RE and mass less than 49 ME. Its mean density is smaller than 2.56 g/cm^3 and orbital period is 9.7566+-0.0012 days. This object, called CoRoT-22 b, adds to a large number of validated Kepler planets. These planets do not have a proper measurement of the mass but allow statistical characterization of the exoplanet population

Hemocompatibility of Silicon-Based Substrates for Biomedical Implant Applications

Silicon membranes with highly uniform nanopore sizes fabricated using microelectromechanical systems (MEMS) technology allow for the development of miniaturized implants such as those needed for renal replacement therapies. However, the blood compatibility of silicon has thus far been an unresolved issue in the use of these substrates in implantable biomedical devices. We report the results of hemocompatibility studies using bare silicon, polysilicon, and modified silicon substrates. The surface modifications tested have been shown to reduce protein and/or platelet adhesion, thus potentially improving biocompatibility of silicon. Hemocompatibility was evaluated under four categories—coagulation (thrombin–antithrombin complex, TAT generation), complement activation (complement protein, C3a production), platelet activation (P-selectin, CD62P expression), and platelet adhesion. Our tests revealed that all silicon substrates display low coagulation and complement activation, comparable to that of Teflon and stainless steel, two materials commonly used in medical implants, and significantly lower than that of diethylaminoethyl (DEAE) cellulose, a polymer used in dialysis membranes. Unmodified silicon and polysilicon showed significant platelet attachment; however, the surface modifications on silicon reduced platelet adhesion and activation to levels comparable to that on Teflon. These results suggest that surface-modified silicon substrates are viable for the development of miniaturized renal replacement systems

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Circulating Microbial Products and Acute Phase Proteins as Markers of Pathogenesis in Lymphatic Filarial Disease

Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients. Dysregulated host inflammatory responses leading to systemic immune activation are thought to play a central role in filarial disease pathogenesis. We measured the plasma levels of microbial translocation markers, acute phase proteins, and inflammatory cytokines in individuals with chronic filarial pathology with (CP Ag+) or without (CP Ag−) active infection; with clinically asymptomatic infections (INF); and in those without infection (endemic normal [EN]). Comparisons between the two actively infected groups (CP Ag+ compared to INF) and those without active infection (CP Ag− compared to EN) were used preliminarily to identify markers of pathogenesis. Thereafter, we tested for group effects among all the four groups using linear models on the log transformed responses of the markers. Our data suggest that circulating levels of microbial translocation products (lipopolysaccharide and LPS-binding protein), acute phase proteins (haptoglobin and serum amyloid protein-A), and inflammatory cytokines (IL-1β, IL-12, and TNF-α) are associated with pathogenesis of disease in lymphatic filarial infection and implicate an important role for circulating microbial products and acute phase proteins

Structural Characterization of CYP51 from Trypanosoma cruzi and Trypanosoma brucei Bound to the Antifungal Drugs Posaconazole and Fluconazole

Chagas Disease is caused by kinetoplastid protozoa Trypanosoma cruzi, whose sterols resemble those of fungi, in both composition and biosynthetic pathway. Azole inhibitors of sterol 14α-demethylase (CYP51), such as fluconazole, itraconazole, voriconazole, and posaconazole, successfully treat fungal infections in humans. Efforts have been made to translate anti-fungal azoles into a second-use application for Chagas Disease. Ravuconazole and posaconazole have been recently proposed as candidates for clinical trials with Chagas Disease patients. However, the widespread use of posaconazole for long-term treatment of chronic infections may be limited by hepatic and renal toxicity, a requirement for simultaneous intake of a fatty meal or nutritional supplement to enhance absorption, and cost. To aid our search for structurally and synthetically simple CYP51 inhibitors, we have determined the crystal structures of the CYP51 targets in T. cruzi and T. brucei, both bound to the anti-fungal drugs fluconazole or posaconazole. The structures provide a basis for a design of new drugs targeting Chagas Disease, and also make it possible to model the active site characteristics of the highly homologous Leishmania CYP51. This work provides a foundation for rational synthesis of new therapeutic agents targeting the three kinetoplastid parasites