Intravenous thrombolysis in stroke attributable to cervical artery dissection.

BACKGROUND AND PURPOSE: Intravenous thrombolysis (IVT) for stroke seems to be beneficial independent of the underlying etiology. Whether this is also true for cervical artery dissection (CAD) is addressed in this study.METHODS: We used the Swiss IVT databank to compare outcome and complications of IVT-treated patients with CAD with IVT-treated patients with other etiologies (non-CAD patients). Main outcome and complication measures were favorable 3-month outcome, intracranial cerebral hemorrhage, and recurrent ischemic stroke. Modified Rankin Scale score <or=1 at 3 months was considered favorable.RESULTS: Fifty-five (5.2%) of 1062 IVT-treated patients had CAD. Patients with CAD were younger (median age 50 versus 70 years) but had similar median National Institutes of Health Stroke Scale scores (14 versus 13) and time to treatment (152.5 versus 156 minutes) as non-CAD patients. In the CAD group, 36% (20 of 55) had a favorable 3-month outcome compared with 44% (447 of 1007) non-CAD patients (OR, 0.72; 95% CI, 0.41 to 1.26), which was less favorable after adjustment for age, gender, and National Institutes of Health Stroke Scale score (OR, 0.50; 95% CI, 0.27 to 0.95; P=0.03). Intracranial cerebral hemorrhages (asymptomatic, symptomatic, fatal) were equally frequent in CAD (14% [7%, 7%, 2%]) and non-CAD patients (14% [9%, 5%, 2%]; P=0.99). Recurrent ischemic stroke occurred in 1.8% of patients with CAD and in 3.7% of non-CAD-patients (P=0.71).CONCLUSIONS: IVT-treated patients with CAD do not recover as well as IVT-treated non-CAD patients. However, intracranial bleedings and recurrent ischemic strokes were equally frequent in both groups. They do not account for different outcomes and indicate that IVT should not be excluded in patients who may have CAD. Hemodynamic compromise or frequent tandem occlusions might explain the less favorable outcome of patients with CAD.

Allorestricted T lymphocytes with a high avidity T-cell receptor towards NY-ESO-1 have potent anti-tumor activity.

The cancer-testis antigen NY-ESO-1 has been targeted as a tumor-associated antigen by immunotherapeutical strategies, such as cancer vaccines. The prerequisite for a T-cell-based therapy is the induction of T cells capable of recognizing the NY-ESO-1-expressing tumor cells. In this study, we generated human T lymphocytes directed against the immunodominant NY-ESO-1(157-165) epitope known to be naturally presented with HLA-A*0201. We succeeded to isolate autorestricted and allorestricted T lymphocytes with low, intermediate or high avidity TCRs against the NY-ESO-1 peptide. The avidity of the established CTL populations correlated with their capacity of lysing HLA-A2-positive, NY-ESO-1-expressing tumor cell lines derived from different origins, e.g. melanoma and myeloma. The allorestricted NY-ESO-1-specific T lymphocytes displayed TCRs with the highest avidity and best anti-tumor recognition activity. TCRs derived from allorestricted, NY-ESO-1-specific T cells may be useful reagents for redirecting primary T cells by TCR gene transfer and, therefore, may facilitate the development of adoptive transfer regimens based on TCR-transduced T cells for the treatment of NY-ESO-1-expressing hematological malignancies and solid tumors.

Induction of cardiac Angptl4 by dietary fatty acids is mediated by peroxisome proliferator-activated receptor beta/delta and protects against fatty acid-induced oxidative stress.

RATIONALE: Although dietary fatty acids are a major fuel for the heart, little is known about the direct effects of dietary fatty acids on gene regulation in the intact heart. OBJECTIVE: To study the effect of dietary fatty acids on cardiac gene expression and explore the functional consequences. METHODS AND RESULTS: Oral administration of synthetic triglycerides composed of one single fatty acid altered cardiac expression of numerous genes, many of which are involved in the oxidative stress response. The gene most significantly and consistently upregulated by dietary fatty acids encoded Angiopoietin-like protein (Angptl)4, a circulating inhibitor of lipoprotein lipase expressed by cardiomyocytes. Induction of Angptl4 by the fatty acid linolenic acid was specifically abolished in peroxisome proliferator-activated receptor (PPAR)beta/delta(-/-) and not PPARalpha(-/-) mice and was blunted on siRNA-mediated PPARbeta/delta knockdown in cultured cardiomyocytes. Consistent with these data, linolenic acid stimulated binding of PPARbeta/delta but not PPARalpha to the Angptl4 gene. Upregulation of Angptl4 resulted in decreased cardiac uptake of plasma triglyceride-derived fatty acids and decreased fatty acid-induced oxidative stress and lipid peroxidation. In contrast, Angptl4 deletion led to enhanced oxidative stress in the heart, both after an acute oral fat load and after prolonged high fat feeding. CONCLUSIONS: Stimulation of cardiac Angptl4 gene expression by dietary fatty acids and via PPARbeta/delta is part of a feedback mechanism aimed at protecting the heart against lipid overload and consequently fatty acid-induced oxidative stress.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Produtividade de grãos e componentes de produção da canola de acordo com fontes e doses de nitrogênio

O objetivo deste trabalho foi avaliar a resposta da canola a fontes e doses de nitrogênio aplicadas na semeadura. O experimento foi conduzido em Latossolo Vermelho distroférrico típico, com textura muito argilosa. Utilizou-se delineamento experimental de blocos ao acaso, em arranjo fatorial 7x2, com sete doses de N em superfície na semeadura (0, 20, 40, 60, 80, 100 e 120 kg ha-1), duas fontes de N (sulfato de amônio e ureia) e quatro repetições. O experimento foi realizado com o híbrido Hyola 61, por dois anos, e foram avaliadas as seguintes variáveis: altura de planta, número de plantas por metro quadrado, massa de matéria seca da parte aérea, massa de síliquas por planta, massa de mil grãos, produtividade de grãos, e teores de proteína e de óleo nos grãos. As variáveis não foram influenciadas pelas fontes de N. A maior produtividade de grãos é alcançada com 88 kg ha-1 de N. Doses crescentes de N aumentam os teores de proteína e diminuem os de óleo nos grãos de canola.

Desenvolvimento vegetativo de pinhão-manso em diferentes arranjos de plantio em sistemas agrossilvipastoris

O objetivo deste trabalho foi avaliar o efeito de diferentes arranjos de plantio no desenvolvimento vegetativo de plantas de pinhão-manso estabelecidas em dois tipos de consórcio agrossilvipastoril. O experimento foi realizado no Município de Coronel Pacheco, MG, em delineamento de blocos ao acaso, em arranjo de parcelas subdivididas. A parcela foi representada por cinco espaçamentos: 6x3 m (555 plantas por hectare), 12x(2x2) m (714 plantas por hectare), 10x(2x2) m (833 plantas por hectare), 8x(2x2) m (1.000 plantas por hectare) e 6x1,5 m (1.111 plantas por hectare); e a subparcela, por dois tipos de consórcio: agrossilvipastoril (integração lavoura-pecuária-pinhão-manso) e silvipastoril (integração pecuária-pinhão-manso). As avalições foram realizadas nas safras 2010/2011 e 2011/2012. O espaçamento de plantio de 6x3 m proporcionou maior desenvolvimento em diâmetro de copa e número de brotações das plantas de pinhão-manso, na safra 2010/2011. Na safra 2011/2012, foi observado maior desenvolvimento em altura com o espaçamento de plantio de 8x(2x2) m. O consórcio de pinhão-manso x milho x pastagem proporciona maior desenvolvimento das plantas de pinhão-manso para todas as variáveis estudadas nas duas safras.

Defining publication bias: protocol for a systematic review of highly cited articles and proposal for a new framework.

BACKGROUND: Selective publication of studies, which is commonly called publication bias, is widely recognized. Over the years a new nomenclature for other types of bias related to non-publication or distortion related to the dissemination of research findings has been developed. However, several of these different biases are often still summarized by the term 'publication bias'. METHODS/DESIGN: As part of the OPEN Project (To Overcome failure to Publish nEgative fiNdings) we will conduct a systematic review with the following objectives:- To systematically review highly cited articles that focus on non-publication of studies and to present the various definitions of biases related to the dissemination of research findings contained in the articles identified.- To develop and discuss a new framework on nomenclature of various aspects of distortion in the dissemination process that leads to public availability of research findings in an international group of experts in the context of the OPEN Project.We will systematically search Web of Knowledge for highly cited articles that provide a definition of biases related to the dissemination of research findings. A specifically designed data extraction form will be developed and pilot-tested. Working in teams of two, we will independently extract relevant information from each eligible article.For the development of a new framework we will construct an initial table listing different levels and different hazards en route to making research findings public. An international group of experts will iteratively review the table and reflect on its content until no new insights emerge and consensus has been reached. DISCUSSION: Results are expected to be publicly available in mid-2013. This systematic review together with the results of other systematic reviews of the OPEN project will serve as a basis for the development of future policies and guidelines regarding the assessment and prevention of publication bias.

Respostas à seleção de características de desempenho em tilápia-do-nilo

Resumo:O objetivo deste trabalho foi estimar parâmetros genéticos e respostas direta e indireta à seleção de características de desempenho em tilápia-do-nilo (Oreochromis niloticus), bem como avaliar o impacto da seleção sobre o ganho genético. Foram utilizadas informações de tilápias-do-nilo, sob seleção em um programa de melhoramento genético, cultivadas em sistema de tanques-rede, de 2008 a 2010. Estimaram-se herdabilidades e correlações genéticas das características ganho em peso diário e, à despesca, peso, largura, altura e comprimento do tronco, além dos ganhos genéticos obtidos com as estimativas de tendências genéticas e das respostas à seleção dessas características. As estimativas de herdabilidade ficaram em torno de 30%. As estimativas de correlações genéticas e de postos foram de alta magnitude. O ganho genético direto para ganho em peso diário foi de 7,9, 5,18 e 9,43%, em 2008, 2009 e 2010, respectivamente. Os ganhos genéticos obtidos a partir das tendências genéticas foram de 6,36, 6,30, 1,62, 1,65 e 1,51%, respectivamente, para ganho em peso diário, peso, largura, altura e comprimento do tronco. O incremento na velocidade de crescimento por meio da seleção impacta positivamente características de desempenho em tilápia-do-nilo.