Vitamin D-related polymorphisms and vitamin D levels as risk biomarkers of COVID-19 disease severity

© 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/.Vitamin D is a fundamental regulator of host defences by activating genes related to innate and adaptive immunity. Previous research shows a correlation between the levels of vitamin D in patients infected with SARS-CoV-2 and the degree of disease severity. This work investigates the impact of the genetic background related to vitamin D pathways on COVID-19 severity. For the first time, the Portuguese population was characterized regarding the prevalence of high impact variants in genes associated with the vitamin D pathways. This study enrolled 517 patients admitted to two tertiary Portuguese hospitals. The serum concentration of 25 (OH)D, was measured in the hospital at the time of patient admission. Genetic variants, 18 variants, in the genes AMDHD1, CYP2R1, CYP24A1, DHCR7, GC, SEC23A, and VDR were analysed. The results show that polymorphisms in the vitamin D binding protein encoded by the GC gene are related to the infection severity (p = 0.005). There is an association between vitamin D polygenic risk score and the serum concentration of 25 (OH)D (p = 0.04). There is an association between 25 (OH)D levels and the survival and fatal outcomes (p = 1.5e-4). The Portuguese population has a higher prevalence of the DHCR7 RS12785878 variant when compared with its prevalence in the European population (19% versus 10%). This study shows a genetic susceptibility for vitamin D deficiency that might explain higher severity degrees in COVID-19 patients. These results reinforce the relevance of personalized strategies in the context of viral diseases.This project was supported by the “Fundação para a Ciência e Tecnologia”, program “Research 4 Covid-19 Apoio especial a projetos de implementação rápida para soluções inovadoras de resposta à pandemia de COVID-19”. It was also partially supported by each institution.info:eu-repo/semantics/publishedVersio

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Recrutamento e seleção na McDonald´s Portugal

Mestrado em Gestão de Recursos HumanosO tema deste Relatório de Estágio incide sobre o recrutamento e seleção na McDonald's Portugal (McDonald's). O objetivo deste trabalho é descrever as atividades realizadas no estágio e estabelecer uma ligação com as metodologias lecionadas ao longo do mestrado. Como tal, foram analisados os processos de recrutamento avaliando se o recrutamento e seleção de pessoas está a ser feito de forma eficaz. Este estudo incidiu no recrutamento e seleção de funcionários e gerentes de turno para os restaurantes da companhia. Para melhor compreender as observações realizadas durante os vários recrutamentos acompanhados, recorremos à literatura principalmente para perceber as considerações que antecedem essa fase, nomeadamente como deve ser feito o planeamento de recursos humanos, como deve ser abordado o tema da flexibilidade no trabalho, entre outros. De forma a obter um termo de comparação, foi também feita uma análise aos processos de recrutamento e seleção de algumas das empresas concorrentes da marca. O presente trabalho está dividido em seis capítulos, o primeiro trata da revisão da literatura, o segundo apresenta a empresa, o terceiro contém a descrição das tarefas realizadas ao longo desse estágio. O quarto capítulo trata da análise dos processos de recrutamento das empresas concorrentes, enquanto o quinto é composto por uma discussão e análise crítica, contendo o sexto capítulo as conclusões deste trabalho, limitações e propostas para investigação futura.The theme of this Internship Report focuses on the recruitment and selection in McDonald's Portugal (McDonald's). The objective of this work is to describe the activities performed on the internship and establish a connection with the methodologies lectured in classes. As such, we analyzed the people recruitment and selection processes in order to try evaluating if it is being done in an effective manner. This study primarily focused on the recruitment and selection of employees and shift managers for the company's restaurants. In order to best understand the observations made during the several recruitment processes followed, we resorted to the literature, mainly to understand the considerations that needed to be made in preparation to this phase, namely how human resources planning should be done, how to take into consideration the theme of labor flexibility, among others. To be able to compare, we also made an analysis of competitor's processes in people recruitment and selection. This work is divided into six chapters, the first being the literature review, the second presents the company, the third describes the tasks performed during the internship. The fourth provides an analysis of the competitor's recruitment processes, while the fifth is composed by a critical analysis and discussion, being the sixth chapter the one that contains this work's conclusions, limitations and suggestions for future research

Functional Impact of vesico-sphincteric disorders in a Multiple Sclerosis patient - a clinical case

Trabalho Final do Mestrado Integrado em Medicina apresentado à Faculdade de MedicinaIntroduction: Multiple Sclerosis is the most prevalent demyelinating inflammatory disease of the Central Nervous System, with 2,200,000 cases worldwide estimated and more than 8,000 in Portugal. More than 80% of patients have vesico-sphincteric disorders with an impact on their daily activities, thus being a comorbidity worthy of intervention. The present clinical case pretends to verify the relevance of Physical Medicine and Rehabilitation intervention in the diagnosis and treatment of vesico-sphincteric disorders, with impact on functionality, quality of life and optimization of the levels of social participation. Clinical Case: Forty one years old male patient with multiple sclerosis, outbreak-remission variant, diagnosed at 21 years old, without significant personal or family history. He presents compatible symptoms with hyperactive neurogenic bladder and the urodynamic study revealed a hypertonic hyperactive bladder with reduced capacity, urethral hypertonia and complete urination. The treatment included behavioral modification techniques associated with pharmacological therapy, with a selective antimuscarinic for M3 receptors, associated with an alpha adrenergic antagonist. Conclusion: Since the urodynamic patterns change over time, tending to progress with the disease, it is necessary to evaluate the urodynamic evolution at regular intervals, in order to optimize the treatment.Introdução: A Esclerose Múltipla é a doença inflamatória desmielinizante do Sistema Nervoso Central mais prevalente, estimando-se que mundialmente existam 2.200.000 casos e mais de 8.000 em Portugal. Mais de 80% dos doentes apresentam alterações vesico-esfincterianas com impacto nas suas atividades de vida diária, sendo portanto uma comorbilidade merecedora de intervenção. O presente caso-clínico pretende verificar a relevância da intervenção da Medicina Física e de Reabilitação no diagnóstico e tratamento das alterações vesico-esfincterianas, com impacto na funcionalidade, na qualidade de vida e na otimização dos níveis de participação social. Caso Clínico: Doente do sexo masculino, de 41 anos, com esclerose múltipla, variante surto-remissão, diagnosticado aos 21 anos, sem antecedentes pessoais ou familiares de relevo. Apresenta sintomatologia compatível com bexiga neurogénica hiperativa e o estudo urodinâmico revelou uma bexiga hiperativa hipertónica com capacidade diminuída, hipertonia uretral e micção completa. O tratamento compreendeu a introdução de técnicas de modificação comportamental associadas a terapêutica farmacológica, com um antimuscarínico seletivo para os recetores M3, associado a um antagonista alfa adrenérgico. Conclusão: Uma vez que os padrões urodinâmicos se modificam ao longo do tempo, tendendo a progredir com a doença, é necessário avaliar a evolução urodinâmica em intervalos regulares, com vista a otimizar o tratamento

Longitudinal data from a school-based intervention - The ACORDA project

The aim of this study was to analyse changes over 8-months of a multidisciplinary school-based intervention program (ACORDA-Project), in body fat, metabolic profile and physical activity (PA). 40 children [22 girls (55%), and 18 boys age=8.4±1.2] of 6 schools participated in a multidisciplinary program during a school year. Blood pressure (BP), physical activity (PA) by accelerometers, percentage of body fat (%BF) and of trunk fat (%TF) by DXA, and plasmatic total cholesterol (TC), triglycerides, HDL-cholesterol, LDL-cholesterol, insulin and glucose were taken at the baseline (Time point 1, TP1) and at the end of the intervention (Time point 2, TP2). General Linear Models (Repeated Measures Analysis of Covariance) was carried out comparing values at baseline vs. final evaluation, with adjustments for gender and age at baseline. Further adjustments were made to relative changes (increase%X) in height, weight, total PA through steps.day-1, sedentary (SEDPA), light (LIGPA) and moderate to vigorous (MVPA) intensities. Relative changes were calculated as: increase%X = (Xfinal � Xbaseline) / Xbaseline. Statistical significance was set at 5%. Eta squared (n2) was used as an indicator of effect size. There was a significant increase of LIGPA and MVPA, (P<0.05), and significant reduction in systolic blood pressure (P<0.05), but not in diastolic blood pressure. For TC and fasting glucose, significant reductions were also found P<0.05). No changes were observed for other traditional cardiovascular risk factors. The present study found that 8-months of multidisciplinary intervention provided a significant increase in PA levels and reduced cardiovascular risk factors in school children, highlighting the importance of this type of intervention through promotion of PA and the positive impact on children health.El objetivo de este estudio fue analizar los cambios en la grasa corporal, el perfil metabólico y la actividad física (AF) en jóvenes escolares que han participado en un programa de intervención multidisciplinario (ACORDA-Project). 40 niños [22 niñas (55%), y 18 niños de edad = 8,4 ± 1,2] de 6 escuelas participaron en un programa multidisciplinario durante un año escolar. La presión arterial (PA), AF por acelerómetros, la porcentaje de grasa corporal (% GC) y de la grasa del tronco (% TF) por DXA, y el colesterol total plasmático (CT), triglicéridos, HDL-colesterol, LDL-colesterol, insulina, la glucosa se tomaron a la línea de base (punto de tiempo 1, TP1) y al final de la intervención (punto de tiempo 2, TP2). Modelos lineales generales (medidas repetidas análisis de covarianza) se utilizaran para la comparación de los valores al inicio del estudio vs. evaluación final, con ajustes para el género y la edad al inicio del estudio. Se hicieron nuevos ajustes a los cambios relativos (incremento%X) de altura, el peso, actividad física total (PA) a través de pasos por día, sedentaria (SEDPA), leve (LIGPA) y de moderada a (MVPA) intensidades vigorosas. Se calcularon los cambios relativos como: incremento%X = (xfinal - Xbaseline) / Xbaseline. La significación estadística se fijó en 5%. Eta cuadrado (n2) se usó como un indicador del tamaño del efecto. Se observó un aumento significativo de LIGPA y MVPA, (P <0.05) y una reducción significativa de la presión arterial sistólica (p <0,05), pero no en la presión arterial diastólica. Para el CT y la glucosa en ayunas, también se encontraron reducciones significativas (P<0.05). No se observaron cambios en otros factores de riesgo cardiovascular tradicionales. El presente estudio encontró que 8-meses de intervención multidisciplinaria proporcionaron un aumento significativo en los niveles de AF y reducción de factores de riesgo cardiovascular en niños en edad escolar. Se destaca la importancia de este tipo de intervención a través de la promoción de la AF y el impacto positivo en la salud de los niño

Prevalence and risk factors of fatty liver in Portuguese adults

© 2020 Stichting European Society for Clinical Investigation Journal FoundationBackground: Prevalence of fatty liver (FL) and nonalcoholic fatty liver disease (NAFLD) depends mainly on obesity, diabetes and genetic factors. FL and NAFLD prevalence was evaluated in Portuguese adult population and correlated with several risk factors and related mortality data, within the same period. Materials and methods: A cross-sectional, population-based multicenter study, voluntary and randomly selected in 834 Portuguese adults (18-79 years). Participants were evaluated after 12-hour fasting. Anthropometric data, past history including alcohol consumption, and associated diseases were registered. Blood samples were collected for biochemical testing. Dietary intake was evaluated using a semi-quantitative food frequency questionnaire. Presence of FL was evaluated using ultrasound, and NAFLD was diagnosed after exclusion of other causes for liver disease. Results: Adjusted prevalence of FL and NAFLD was 37.8% and 17.0%, respectively. FL individuals were older, more frequently males, with increased probability of having obesity, diabetes or harmful alcohol consumption (HAC). NAFLD individuals were also older, but had a similar sex distribution and an increased probability of obesity and diabetes. In both groups, no differences were found regarding dietary pattern or physical activity. During the same time period, nonalcoholic steatohepatitis (NASH) liver-related deaths in Portugal were 0.105/100 000, while alcohol-related liver disease mortality was 6.790/100 000. Conclusion: The large spectrum of FL was present in more than one third of the population, although only less than half could be classified as NAFLD. Other significant risk factors, such as HAC, are probably implicated in FL, explaining the low NASH-related mortality compared with the high alcohol-related mortality during the same time period.The present study received grants from: Portuguese Association for the Study of the Liver (APEF), Gilead Foundation and Gilead Genesis and Roche supplied laboratorial kits. APEF, Gilead Foundation and Gilead Genesis and Roche had no role in the design, analysis or writing of this article, and in the decision to submit the article for publication.info:eu-repo/semantics/publishedVersio