Convergent genetic and expression data implicate immunity in Alzheimer's disease

Background Late–onset Alzheimer's disease (AD) is heritable with 20 genes showing genome wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease we extended these genetic data in a pathway analysis. Methods The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (p = 3.27×10-12 after multiple testing correction for pathways), regulation of endocytosis (p = 1.31×10-11), cholesterol transport (p = 2.96 × 10-9) and proteasome-ubiquitin activity (p = 1.34×10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected p 0.002 – 0.05). Conclusions The immune response, regulation of endocytosis, cholesterol transport and protein ubiquitination represent prime targets for AD therapeutics

Use of conventional cardiac troponin assay for diagnosis of non-ST-elevation myocardial infarction: 'The Ottawa Troponin Pathway'.

BACKGROUND:Serial conventional cardiac troponin (cTn) measurements 6-9 hours apart are recommended for non-ST-elevation MI (NSTEMI) diagnosis. We sought to develop a pathway with 3-hour changes for major adverse cardiac event (MACE) identification and assess the added value of the HEART [History, Electrocardiogram (ECG), Age, Risk factors, Troponin] score to the pathway. METHODS:We prospectively enrolled adults with NSTEMI symptoms at two-large emergency departments (EDs) over 32-months. Patients with STEMI, unstable angina and one cTn were excluded. We collected baseline characteristics, Siemens Vista conventional cTnI at 0, 3 or 6-hours after ED presentation; HEART score predictors; disposition and ED length of stay (LOS). Adjudicated primary outcome was 15-day MACE (acute MI, revascularization, or death due to cardiac ischemia/unknown cause). We analyzed multiples of 99th percentile cut-off cTnI values (45, 100 and 250ng/L). RESULTS:1,683 patients (mean age 64.7 years; 55.3% female; median LOS 7-hours; 88 patients with 15-day MACE) were included. 1,346 (80.0%) patients with both cTnI≤45 ng/L; and 155 (9.2%) of the 213 patients with one value≥100ng/L but both45ng/L but99th percentile, standardize management and reduce the ED LOS

Eugenia e Fundação Rockefeller no Brasil: a saúde como proposta de regeneração nacional Eugenics and the Rockefeller Foundation in Brazil: health as an instrument of national regeneration

Nas primeiras décadas do século XX, a Fundação Rockefeller atuou de modo decisivo na implementação de ações voltadas para a saúde pública no Brasil, especialmente naquilo denominado de movimento sanitarista. Nesse mesmo período, a eugenia brasileira era equivalente ao sanitarismo, onde defendia-se a máxima de que "sanear era eugenizar". Vários trabalhos discutem o movimento sanitário, a questão da saúde pública no Brasil, a Fundação Rockefeller, a eugenia e seus ativistas. Entretanto, é escassa a discussão a respeito da Rockefeller e o movimento eugenista brasileiro. É necessário alertar que embora nos deparemos com questões ligadas à raça, teorias sobre genética ou evolução, este trabalho não tem como objetivo analisar tais assuntos com profundidade. O que buscamos construir foi o cenário no qual a eugenia de maneira geral, e a brasileira, especificamente, se desenrolou trazendo à tona as posturas de alguns eugenistas brasileiros.<br>In the first decades of the twentieth century, the work of the Rockefeller Foundation was decisive for the implementation of public health initiatives in Brazil, especially in the so-called public health movement. At that time, Brazilian eugenics was the same as public health, as expressed in the maxim "to sanitize is to eugenize". There are several studies discussing the public health movement, the issue of public health in Brazil, the Rockefeller Foundation, eugenics and its supporters. However, there is little discussion on the relationship between the Rockefeller Foundation and the Brazilian eugenics movement. It is worth to mention that although there are issues related to race, and theories on genetics and evolution, this work does not intend to examine these issues in depth. The aim was to recreate the scenario in which eugenics in general, and particularly in the Brazilian case, was developed, exposing the positions of some of the Brazilian eugenicists