Functional annotation signatures of disease susceptibility loci improve SNP association analysis.

BACKGROUND: Genetic association studies are conducted to discover genetic loci that contribute to an inherited trait, identify the variants behind these associations and ascertain their functional role in determining the phenotype. To date, functional annotations of the genetic variants have rarely played more than an indirect role in assessing evidence for association. Here, we demonstrate how these data can be systematically integrated into an association study's analysis plan. RESULTS: We developed a Bayesian statistical model for the prior probability of phenotype-genotype association that incorporates data from past association studies and publicly available functional annotation data regarding the susceptibility variants under study. The model takes the form of a binary regression of association status on a set of annotation variables whose coefficients were estimated through an analysis of associated SNPs in the GWAS Catalog (GC). The functional predictors examined included measures that have been demonstrated to correlate with the association status of SNPs in the GC and some whose utility in this regard is speculative: summaries of the UCSC Human Genome Browser ENCODE super-track data, dbSNP function class, sequence conservation summaries, proximity to genomic variants in the Database of Genomic Variants and known regulatory elements in the Open Regulatory Annotation database, PolyPhen-2 probabilities and RegulomeDB categories. Because we expected that only a fraction of the annotations would contribute to predicting association, we employed a penalized likelihood method to reduce the impact of non-informative predictors and evaluated the model's ability to predict GC SNPs not used to construct the model. We show that the functional data alone are predictive of a SNP's presence in the GC. Further, using data from a genome-wide study of ovarian cancer, we demonstrate that their use as prior data when testing for association is practical at the genome-wide scale and improves power to detect associations. CONCLUSIONS: We show how diverse functional annotations can be efficiently combined to create 'functional signatures' that predict the a priori odds of a variant's association to a trait and how these signatures can be integrated into a standard genome-wide-scale association analysis, resulting in improved power to detect truly associated variants

45S5 bioglass-derived glass-ceramic scaffolds containing niobium obtained by gelcasting method

Scaffolds of bioglass derived from BG45S5 (45 wt% SiO2, 24.5 wt% CaO, 24.5 wt% Na2O and 6 wt% P2O5) containing 10 wt% niobium were prepared by gelcasting method. The scaffolds presented a 3D porous structure with interconnected and spherical pores (pore size range 100 µm to 500 µm) and high porosity (89%), similar to trabecular architecture of spongy bone. The compressive strength was 0.18 ± 0.03 MPa which is acceptable for bone repair applications. The in vitro biological studies showed cytocompatibility for human osteoblastic cells as well tendency for higher alkaline phosphatase activity. Therefore, the findings here suggest the great potential of the scaffolds for using in bone tissue engineering.This work was supported by São Paulo Research Foundation - FAPESP (Grant: 2015-24659-7), National Council for Scientific and Technological Development (Grant: 456461/2014-0) and Erasmus Mundus Program (Be Mundus Project). The authors acknowledge the use of the analytical instrumentation facility at I3S-Instituto de Investigação e Inovação em Saúde (Portugal) and the provision of Nb2O5 by CBMM - Companhia Brasileira de Metalurgia e Mineração

Influence of PLLA/PCL/HA scaffold fiber orientation on mechanical properties and osteoblast behavior

Scaffolds based on aligned and non-aligned poly (L-lactic acid) (PLLA)/polycaprolactone (PCL) fibers obtained by electrospinning, associated to electrosprayed hydroxyapatite (HA) for tissue engineering applications were developed and their performance was compared in terms of their morphology and biological and mechanical behaviors. The morphological results assessed by scanning electron microscopy showed a mesh of PLLA/PCL fibers (random and perfectly aligned) associated with aggregates of nanophased HA. Fourier transform infrared spectrometry confirmed the homogeneity in the blends and the presence of nanoHA in the scaffold. As a result of fiber alignment a 15-fold increase in Young's Modulus and an 8-fold increase in tensile strength were observed when compared to non-aligned fibers. In PLLA/PCL/HA scaffolds, the introduction of nanoHA caused a remarkable improvement of the mechanical strength of this material acting as a reinforcement, enhancing the response of these constructs to tensile stress. In vitro testing was evaluated using osteoblast (MC3T3-E1) cells. The results showed that both fibrous scaffolds were able to support osteoblast cell adhesion and proliferation and that fiber alignment induced increased cellular metabolic activity. In addition, the adhesion and proliferation of Staphylococcus aureus were evaluated and a lower number of colony forming units (CFUs) was obtained in the scaffolds with aligned fibers.Project UID/BIM/04293/2019 by FCT/MCTES through Portuguese Funds

Violência autoinfligida por intoxicação exógena em um serviço de urgência e emergência

RESUMO Objetivo Analisar as violências autoinfligidas por intoxicação exógena notificadas em um serviço de saúde. Métodos Estudo epidemiológico, retrospectivo e analítico realizado em um serviço de urgência e emergência do município de Teresina, Piauí. Procedeu-se nos meses de janeiro e fevereiro de 2015, mediante análise de todos os casos de violência autoinfligida por intoxicação exógena notificados no Sistema de Informação de Agravos de Notificação, no período de 2009 a 2014. O teste qui-quadrado de Pearson foi utilizado na análise. Resultados Foram notificadas 277 vítimas de violência autoinfligida por intoxicação exógena, sendo que 10,5% morreram por suicídio. Houve associação entre o óbito e as variáveis idade, escolaridade, zona de ocorrência e tipo de exposição, assim como entre o tipo de exposição e a quantidade de agentes utilizados. Conclusão Os resultados fornecem subsídios para a definição de estratégias de prevenção considerando os grupos vulneráveis e a complexidade dos fatores associados à violência autoinfligida

Alterações na composição corporal a partir da prática do stand up paddle

Introdução: O Stand Up Paddle (SUP) é um esporte aquático que tem se tornado popular em todo o mundo ao longo dos últimos anos. Objetivo: Avaliar as alterações na composição corporal a partir da prática do SUP em dois indivíduos sedentários. Métodos: A pesquisa foi composta por uma Mulher (25 anos) e um homem (26 anos) sedentários. Para avaliar o nível de atividade física foi utilizado IPAQ. Antecipando o início do treinamento foram coletados os dados antropométricos de massa corporal e estatura para cálculo do índice de massa corporal (IMC). Foram feitas avaliações de dobras cutâneas para obtenção do percentual de gordura (%G). Também foram coletados os dados de circunferências e os diâmetros dos biepicôndilos do fêmur e do úmero para calcular o somatotipo. Os treinamentos foram por 8 semanas. Para a determinação do somatotipo utilizou-se o método proposto por Heath e Carter (1967). Para a análise dos dados realizou-se o ∆ de variação entre pré e pós teste. Resultados: A prática do SUP apresentou alterações positivas, melhorando as variáveis da composição corporal dos avaliados. Conclusão: O SUP pode ser utilizado como uma atividade física benéfica para a saúde e qualidade de vida. ABSTRACT Changes in Body Composition from Stand Up Paddle PracticeIntroduction: The Stand Up Paddle (SUP) is an aquatic sport that has become popular all over the world over the past few years. Objective: To evaluate changes in body composition from the practice of SUP in two sedentary individuals. Methods: The research was composed by a Woman (25 years) and a man (26 years) sedentary. To assess the level of physical activity, IPAQ was used. Anticipating the beginning of the training, the anthropometric data of body mass and height were collected to calculate the body mass index (BMI). Skin folds were evaluated to obtain the percentage of fat (%BF). We also collected circumferential data and diameters of the femur and humerus biepicondilos to calculate the somatotype. The trainings were for 8 weeks. For the determination of the somatotype the method proposed by Heath and Carter (1967) was used. For the analysis of the data the Δ of variation between pre and post test was performed. Results: The practice of SUP presented positive changes, improving the variables of the body composition of the evaluated ones. Conclusion: SUP can be used as a physical activity beneficial to health and quality of life

Efeito de diferentes tratamentos t?rmicos sobre microestrutura e microdureza de um sistema a?o C-Mn/revestimento de inconel 625.

A utiliza??o de tubos de a?o C-Mn na ind?stria de ?leo e g?s ? muito comum desde o nascimento desta ind?stria. Mesmo com a grande evolu??o da metalurgia destes a?os ao longo das ?ltimas d?cadas, o desafio de desempenho em ambientes severos de corros?o devido ?s caracter?sticas reativas (H2S, CO2) do petr?leo e seus derivados, imp?em uma nova era para a fabrica??o de tubos. A solu??o tecnol?gica mais direta seria a utiliza??o de a?os com alta liga (Ni, Cr) e/ou superligas de n?quel. No entanto, os custos de produ??o tornariam invi?veis pelo alto custo destes materiais. Neste contexto, ? crescente iniciativas de pesquisas para o desenvolvimento de overlay e/ou cladding, ou seja, revestimentos de a?os C-Mn usando superligas de n?quel e a?os inoxid?veis. Neste trabalho, foi utilizada a deposi??o de uma camada da superliga de n?quel Inconel 625 atrav?s do processo laser. Uma das desvantagens da deposi??o a laser ou qualquer outro processo de fus?o ? a forma??o de uma regi?o de descontinuidade microestrutural no a?o, chamada de ZTA (zona termicamente afetada pelo calor). Neste estudo, diferentes rotas de tratamentos t?rmicos foram investigadas com o objetivo de eliminar a ZTA e preservar as caracter?sticas originais do substrato e do revestimento.The application of C-Mn steel pipe in the oil & gas industry is quite common since starting of this industry. Even with the great evolution of the metallurgy of this type of steel over the last decades, the challenge is to overcome the corrosion severity caused by sour (H2S, CO2) species present in the petroleum and its derivates. The direct technological solution would be to replace the C-Mn steel by Ni-based superalloys and/or stainless steels. However, the high costs of these materials would make several projects impracticable. In this context, there are several initiatives in order to develop overlay and/or cladding, that means, coatings of C-Mn steels using superalloys and stainless steels. In this work, it was used an overlay deposition of Inconel 625 on the surface of a C-Mn steel using the laser process. A disadvantage of laser deposition, as it is for any deposition melting process, is the formation of a microstructural discontinuity in the steel substrate caused by the thermal cycle (HAZ = heat affected zone). In this study, different heat treatment routes were investigated aiming to eliminate the HAZ preserving the original characteristics of the substrate and of the coating

A three-year longitudinal evaluation of the forearm bone density of users of etonogestrel- and levonorgestrel-releasing contraceptive implants

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to evaluate bone mineral density (BMD) at baseline and at 18 and 36 months of use of etonogestrel (ENG)-and levonorgestrel (LNG)-releasing contraceptive implants. This is a continuation of a previous study in which BMD was evaluated at baseline and at 18 months of use.</p> <p>Methods</p> <p>A total of 111 women, 19–43 years of age, wererandomly allocated to use one of the two implants. At 36 months of follow-up, only 36 and 39 women were still using the ENG- and LNG-releasing implants, respectively. BMD was evaluated at the distal and at the ultra-distal radius of the non-dominant forearm using dual-energy X-ray absorptiometry.</p> <p>Results</p> <p>There was no difference in the BMD of users of either implant at 18 and at 36 months. BMD was significantly lower at 18 and at 36 months at the distal radius in both groups of users compared to pre-insertion values; however, no difference was found at the ultra-distal radius.</p> <p>Conclusion</p> <p>Women 19–43 years of age using either one of these two contraceptive implants for 36 months had lower BMD values at the distal radius compared to pre-insertion values; however, no difference was found at the ultra-distal radius.</p