Association between the adrenoreceptor β2 gene and pediatric asthma severity – a study of the PACMAN cohort

"Pharmacogenetics of Asthma medication in Children: Medication with Anti-Inflammatory effects" (PACMAN) is an observational retrospective pharmacy-based study carried out in 2009, in the Netherlands, aiming to investigate the effects of genetic variation on treatment response to asthma medication in children and to identify (profiles of) SNPs that characterize response phenotypes. Data on respiratory symptoms and medication use, including medication type and amount, was collected from pharmaceutical records of asthmatic children and data on the children’s sex, age, genetic traits, and ethnicity. We aimed to assess the association between asthma severity and the Arg16Glu polymorphism of the β2 adrenoreceptor gene (ADRB2). This gene is expressed in bronchial muscle cells, which is involved in the physiological response of the airway response and has been associated with clinical drug response and asthma exacerbations. We used the PACMAN data and considered the dispensing of oral corticosteroid prescriptions as a proxy of the disease severity since corticoids are commonly used in uncontrolled asthmatic states (exacerbations). We considered two different genetic models – additive and genotypic, which can be translated for analysis purposes into a numeric format, corresponding to the number of copies of the minor allele, and categorical (each genotype representing a category), respectively. We used models of the class of the Generalized Linear Mixed Models for count data with excess of zeros, namely zero-inflated and hurdle models, considering a Negative Binomial distribution to account for overdispersion. Both models included the polymorphism in the zero and count components and were adjusted for children’s baseline characteristics. In both approaches to deal with the excess of zeros, a significant effect of the polymorphism was found only in the binary component of the models. In the count component, only sex and age showed a significant effect. This points towards the existence of an effect of the polymorphism in the presence of asthma exacerbations, with not shown effect in the frequency of OCS prescription.This work is partially financed by national funds through FCT – Fundação para a Ciência e a Tecnologia under the project UIDB/00006/2020.info:eu-repo/semantics/publishedVersio

Proteoforms of transthyretin - candidate biomarkers in diagnosis of obstructive sleep

Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder which is characterized by recurrent occurrence of partial or complete closure of the upper airway during sleep, despite ongoing efforts to breathe. The majority of patients with OSA remain undiagnosed since most of them only come to the attention of a clinician when they complain of daytime sleepiness or when their bed partners report loud snoring or witnessed apnea episodes.Epidemiological studies have indicated that OSA affects 6–13% of the adult population. OSA is multifactorial disease, also considered as metabolic syndrome, which diagnosis in early stages is challenging thus often remain undiagnosed. Recently was found connection between transthyretin (TTR) protein modifications present in human plasma samples and appearance of sleep apnea syndrome1,2 . Mass Spectrometric Immunoassay (MSIA) was successfully applied previously on identification of and quantification of TTR variants present in human serum3. We took advantage on this powerful method to investigate possible modifications of TTR proteoforms in patients with OSAS.N/

Sex differences in functional connectivity between resting state brain networks in Autism Spectrum Disorder

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Functional brain connectivity (FBC) has previously been examined in autism spectrum disorder (ASD) between-resting-state networks (RSNs) using a highly sensitive and reproducible hypothesis-free approach. However, results have been inconsistent and sex differences have only recently been taken into consideration using this approach. We estimated main effects of diagnosis and sex and a diagnosis by sex interaction on between-RSNs FBC in 83 ASD (40 females/43 males) and 85 typically developing controls (TC; 43 females/42 males). We found increased connectivity between the default mode (DM) and (a) the executive control networks in ASD (vs. TC); (b) the cerebellum networks in males (vs. females); and (c) female-specific altered connectivity involving visual, language and basal ganglia (BG) networks in ASD-in suggestive compatibility with ASD cognitive and neuroscientific theories.VT received support from Fundação Ciência e Tecnologia (FCT) PhD fellowship (PD/BD/114460/2016) and paid by FCT DSAIPA/DS/0065/2018 Grant. DP was supported by the European Commission Seventh Framework Programme Marie Curie Career Integration Grant FP7-PEOPLE-2013-CIG-631952, the 2016 Bial Foundation Psychophysiology Grant Ref. 292/16, and the IF/00787/2014, LISBOA-01-0145-FEDER-030907 and DSAIPA/DS/0065/2018 FCT Grants, and the iMM Lisboa Director’s Fund Breakthrough Idea Grant 2016; and is co-founder and shareholder of the neuroimaging research services company NeuroPsyAI, Ltd. MA was supported by FCT Grant UID/MAT/00006/2013.info:eu-repo/semantics/publishedVersio

Biomarkers of Presbycusis and Tinnitus in a Portuguese Older Population

Introduction: Presbycusis or age-related hearing loss (ARHL) is a ubiquitous health problem. It is estimated that it will affect up to 1.5 billion people by 2025. In addition, tinnitus occurs in a large majority of cases with presbycusis. Glutamate metabotropic receptor 7 (GRM7) and N-acetyltransferase 2 (NAT2) are some of the genetic markers for presbycusis. Objectives: To explore patterns of hearing loss and the role of GRM7 and NAT2 as possible markers of presbycusis and tinnitus in a Portuguese population sample. Materials and Methods: Tonal and speech audiometry, tinnitus assessment, clinical interview, and DNA samples were obtained from patients aged from 55 to 75 with or without tinnitus. GRM7 analysis was performed by qPCR. Genotyping of single nucleotide polymorphisms (SNPs) in NAT2 was performed by PCR amplification followed by Sanger sequencing or by qPCR. Results: We screened samples from 78 individuals (33 men and 45 women). T allele at GRM7 gene was the most observed (60.3% T/T and 33.3% A/T). Individuals with a T/T genotype have a higher risk for ARHL and 33% lower risk for tinnitus, compared to individuals with A/A and A/T genotype, respectively. Being a slow acetylator (53%) was the most common NAT2 phenotype, more common in men (55.8%). Intermediate acetylator was the second most common phenotype (35.9%) also more frequent in men (82.6%). Noise exposed individuals and individuals with ‘high frequency’ hearing loss seem to have a higher risk for tinnitus. Our data suggests that allele AT of GRM7 can have a statistically significant influence toward the severity of tinnitus. Conclusion: For each increasing year of age the chance of HL increases by 9%. The risk for ARHL was not significantly associated with GRM7 neither NAT2. However, we cannot conclude from our data whether the presence of T allele at GRM7 increases the odds for ARHL or whether the A allele has a protective effect. Genotype A/T at GRM7 could potentially be considered a biomarker of tinnitus severity. This is the first study evaluating the effect of GRM7 and NAT2 gene in tinnitus

The role of DNA concentrations in forensic casework results : regression models application

Póster apresentado no 28th Congress of International Society For Forensic Genetics (ISFG 2019), Praga, República Checa, 9-13 de Setembro de 2019In forensic DNA typing, short tandem repeats (STRs) are the most frequently genotyped markers in order to distinguish between individuals and to relate them to a crime or to exonerate the innocent. In recent years, new controversies have arisen with the advent of more sensitive techniques, allowing profiles to be recovered from minimum amounts of DNA, hence, bringing challenges to weight of evidence evaluation for forensic DNA profiles obtained from low template DNA samples. Introduction of interpretation models, or even new weight of evidence software should be accompanied by a measure of uncertainty that is part of any biological analysis. Specially, due to stochastic effects, the reliability of the obtained profiles might differ between machinery, workflow and also PCR settings in use in different laboratories. In this work we try to understand the relation between Peak Area, DNA concentration and also size marker, using adequate regression models. Buccal swabs from 180 individuals, with unknown identity, were selected for this study. DNA was extracted with prep-n-go™ buffer and quantified using Quantifiler® Trio DNA Quantification kit in a 7500 Real-Time PCR System (Applied Biosystems). STR amplification was performed with Powerplex Fusion 6C amplification kit (Promega). Amplified PCR products were separated and detected in an Applied Biosystems® 3500 Genetic Analyzer using manufacturer’s conditions. Electrophoresis results were analysed with GeneMapper® ID-X v1.4. Statistical analysis was performed with R Studio. Our results allow having an important overview about the relation between DNA concentrations, peak area, and size of the studied genetic markers.N/

Early father–child and mother–child attachment relationships: contributions to preschoolers’ social competence

The main goal of this study was to explore the contributions of early father-child and mother-child attachment relationships to children's later social competence with their preschool peers; possible unique and shared contributions were tested. Using a multi-method design and focusing on direct observation, attachment was assessed at home at age 3 with the Attachment Behavior Q-sort (AQS) and two years later social competence was assessed at classrooms of 5-year-olds using a set of seven measurement indicators that are part of the Hierarchical Model of Social Competence. Results show that attachment to each parent made unique and significant contributions to children's social competence and suggested the possibility that each caregiver may have somewhat different patterns of influence on the different indicators of children's social competence. Findings also suggest the possibility that a secure attachment with one parent may buffer the impact of having an insecure relationship with the other. Due to sample size, these results should be seen as a starting point to generate new and larger studies.info:eu-repo/semantics/publishedVersio

Nexos Interdisciplinares entre Teoria Crítica e gênero: aspectos filosóficos, psicológicos e educacionais

Este artigo pretende realizar um debate sobre as diferentes abordagens teórico-metodológicas referentes aos artigos que compõem o Dossiê "Nexos Interdisciplinares entre Teoria Crítica e Gênero", fundamentando suas análises por meio da Teoria Crítica da Sociedade. O objetivo é pensar o que acontece quando a Teoria Crítica da Sociedade inclina-se para pensar os temas e problemas próprios aos estudos de gênero. Destaca-se, de antemão, a necessária abordagem interdisciplinar própria às pesquisas em torno das temáticas de gênero; assim como a interface entre estudos e pesquisas empíricas e debates epistemológicos implicados e engajados. Este artigo, no início do dossiê, irá não apenas fazer uma reconstrução da diversidade dos materiais que o compõem, mas também pensar criticamente sobre o que está em questão como possível unidade temática que atravessa os diferentes trabalhos. Pretende-se, assim, identificar os pontos de convergência que emergem, como hubs principais, dessa rede de debate em que se cruzam os nexos entre Teoria Crítica e Gênero, sobretudo, em seus aspectos filosóficos, psicológicos e educacionais

PROJETOS DE TRABALHO: PERCEPÇÕES DE PROFESSORES E ALUNOS QUANTO SUA EFICÁCIA COMO ESTRATÉGIA DE ENSINO

This study aims to analyze the development and implementation of a work project, and the promotion of health as a pivotal point, as well as the perception of teachers and students about its effectiveness as a teaching strategy. To address the above goals we conducted a case study, through collaborative action research. The study subjects were 10 teachers and 12 high school students from a state school education of a city in the interior of Rio Grande do Sul and two university students from the Physical Education course. To develop the project weekly meetings were held two hours during a semester, and the same developed in five distinct steps: definition of the generating situation; questioning and objectives; activities / tasks; socialization of results and evaluation. The data was produced from observations during the experiment and content of research reports and questionnaires, being grouped into two areas: reporting experience in the local context; and the perceptions of those involved as its contribution as a teaching methodology. The results showed: learning to work in an interdisciplinary way, professional growth, motivation and reflection on the pedagogical practice for teachers; a better understanding of the subject, the motivation to learn, a greater appreciation of the school and the importance of teamwork for students; the search for new learning, the improvement of their professional performance; and learning to work in teams, to academic researchers. Despite some difficulties in the implementation of this proposal, it can be concluded that the design work was constituted as a significant strategy for everyone involved in the proposal, pointing to its effectiveness as a teaching methodology.Este estudo tem como objetivo analisar o processo de desenvolvimento e aplicação de um projeto de trabalho, tendo a promoção da saúde como eixo articulador, assim como a percepção de professores e alunos sobre sua eficácia como estratégia de ensino. Para contemplar os objetivos citados foi realizado um estudo de caso, por meio da pesquisa-ação colaborativa. Os sujeitos do estudo foram 10 professores e 12 alunos do ensino médio de uma escola da rede estadual de ensino de um município do interior do Rio Grande do Sul e dois universitários universitários do curso de Educação Física. Para o desenvolvimento do projeto foram realizados encontros semanais de duas horas, durante um ano letivo. O projeto de trabalho foi desenvolvido em cinco etapas: definição da situação geradora; problematização e objetivos; atividades/tarefas; socialização dos resultados e avaliação. Os dados foram produzidos a partir das observações durante a experiência e do conteúdo dos relatórios de pesquisa e questionários, sendo agrupados em dois eixos: relato da experiência no contexto local; e, as percepções dos sujeitos envolvidos quanto à eficácia dos projetos de trabalho como metodologia de ensino. Os resultados apontaram para: o aprender a trabalhar de forma interdisciplinar, o crescimento profissional, a motivação e a reflexão sobre a prática pedagógica, para os professores; o melhor entendimento do assunto, a motivação para o aprender, uma maior valorização da escola e a importância do trabalho em equipe, para os alunos; a busca por aprendizagens novas, a melhora do seu desempenho profissional; e, o aprender a trabalhar em equipe, para os universitários pesquisadores. Pode-se concluir que o projeto de trabalho se constituiu como uma estratégia significativa para todos os envolvidos apontando para a sua eficácia enquanto estratégia metodológica de ensino