Flying under the radar - impact and factors influencing asymptomatic DENV infections

The clinical outcome of DENV and other Flaviviruses infections represents a spectrum of severity that ranges from mild manifestations to severe disease, which can ultimately lead to death. Nonetheless, most of these infections result in an asymptomatic outcome that may play an important role in the persistent circulation of these viruses. Also, although little is known about the mechanisms that lead to these asymptomatic infections, they are likely the result of a complex interplay between viral and host factors. Specific characteristics of the infecting viral strain, such as its replicating efficiency, coupled with host factors, like gene expression of key molecules involved in the immune response or in the protection against disease, are among crucial factors to study. This review revisits recent data on factors that may contribute to the asymptomatic outcome of the world's widespread DENV, highlighting the importance of silent infections in the transmission of this pathogen and the immune status of the host.The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by FCT-Fundação para a Ciência e a Tecnologia (Project ref.PTDC/SAU-INF/30440/2017). Paulo Henriques was suported by ARDITI (Agência Regional para o Desenvolvimento da Investigação Tecnologia e Inovação) through a PhD Grant (M1420-09-5369-FSE-000001)

Flying under the radar – impact and factors influencing asymptomatic DENV infections

The clinical outcome of DENV and other Flaviviruses infections represents a spectrum of severity that ranges from mild manifestations to severe disease, which can ultimately lead to death. Nonetheless, most of these infections result in an asymptomatic outcome that may play an important role in the persistent circulation of these viruses. Also, although little is known about the mechanisms that lead to these asymptomatic infections, they are likely the result of a complex interplay between viral and host factors. Specific characteristics of the infecting viral strain, such as its replicating efficiency, coupled with host factors, like gene expression of key molecules involved in the immune response or in the protection against disease, are among crucial factors to study. This review revisits recent data on factors that may contribute to the asymptomatic outcome of the world’s widespread DENV, highlighting the importance of silent infections in the transmission of this pathogen and the immune status of the host

Vimentin Diversity in Health and Disease

Vimentin is a protein that has been linked to a large variety of pathophysiological conditions, including cataracts, Crohn’s disease, rheumatoid arthritis, HIV and cancer. Vimentin has also been shown to regulate a wide spectrum of basic cellular functions. In cells, vimentin assembles into a network of filaments that spans the cytoplasm. It can also be found in smaller, non-filamentous forms that can localise both within cells and within the extracellular microenvironment. The vimentin structure can be altered by subunit exchange, cleavage into different sizes, re-annealing, post-translational modifications and interacting proteins. Together with the observation that different domains of vimentin might have evolved under different selection pressures that defined distinct biological functions for different parts of the protein, the many diverse variants of vimentin might be the cause of its functional diversity. A number of review articles have focussed on the biology and medical aspects of intermediate filament proteins without particular commitment to vimentin, and other reviews have focussed on intermediate filaments in an in vitro context. In contrast, the present review focusses almost exclusively on vimentin, and covers both ex vivo and in vivo data from tissue culture and from living organisms, including a summary of the many phenotypes of vimentin knockout animals. Our aim is to provide a comprehensive overview of the current understanding of the many diverse aspects of vimentin, from biochemical, mechanical, cellular, systems biology and medical perspectives

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

Purinas, creatina, metilação deficiente e sua interrelação bioquímica e clínica

Marinus Duran; Isabel G. Tavares de Almeida; Helena P. Gaspar Tomá

Homocysteine Metabolism in Children and Adolescents: Influence of Age on Plasma Biomarkers and Correspondent Genotype Interactions

Background: Imbalance of homocysteine (Hcy) metabolism links with several pathologies; nevertheless, it is poorly characterized in pediatric populations. This study investigated the impact of age on plasma concentrations of Hcy and relevant biomarkers along with correspondent genotype interactions. Methods: A healthy pediatric cohort aged 9 (n = 195) and 17 (n = 128) years old (yo) was studied. Immunoassays and GC-MS-SIM-mode quantified plasma levels of Hcy and biomarkers. PCR-RFLP or quantitative-PCR assays assessed common variations in related genes. Results: Age impacted on levels of Hcy and metabolic markers: older children presented with the lowest folates and total-cobalamin (tCbl), while with the highest Hcy concentrations, whereas methylmalonic acid (MMA) and holotranscobalamin (Holo-TC) levels remained similar in 9-yo and 17-yo children. The relationships between B-vitamins and metabolic markers were also dependent on age. Only in the older children, MMA correlated with tCbl and Holo-TC, and MMA levels were markedly higher in the 17-yo subjects presenting with the lowest quartiles of Holo-TC concentrations. Lastly, age also impacted on the correlations between genotype and biomarkers. In the 17-yo group, however not in the 9-yo children, tHcy differed between MTHFR 677 genotypes, with subjects who had the MTHFR 677TT genotype displaying the highest tHcy concentrations. Conclusions: Age impacts on the Hcy metabolism dynamics in a pediatric population

HIPERTENSÃO ARTERIAL SISTÊMICA AUTORREFERIDA: ESTUDO POPULACIONAL

Objetivo: Estimar a prevalência de hipertensão arterial sistêmica autorreferida e associar com o perfil sociodemográfico, estilo de vida, uso dos serviços de saúde e percepção de saúde geral em população residente em Montes Claros, Minas Gerais, Brasil. Métodos: Estudo analítico, observacional e transversal, de base populacional e domiciliar. O instrumento de coleta de dados foi embasado em questionário proposto pelo Ministério da Saúde para avaliar comportamentos e fatores de risco para as doenças crônicas não transmissíveis. O levantamento da prevalência de hipertensão arterial sistêmica foi a partir de relato do pesquisado. Na análise estatística utilizou-se do teste qui quadrado de Pearson e do teste t (student). Ambos os testes consideraram o nível de significância p <0,05. Resultados: Participaram do estudo 2150 indivíduos, com 18 anos ou mais. A prevalência de hipertensão autorreferida foi de 26,0% e foi associada ao sexo feminino, aos idosos, àqueles sem união estável/casados, aos ex-tabagistas, aos consumidores de bebidas alcoólicas no último mês, aos possuidores de plano de saúde, aos usuários do serviço público de saúde em consultas médicas e entre os que autoavaliaram a saúde geral como regular ou ruim (p<0,05). A maior média de consultas e de internações no setor público de saúde foi para o grupo de hipertensos (p<0,05). Conclusão: A prevalência de Hipertensão Arterial Sistêmica foi semelhante à da população brasileira. A hipertensão foi associada ao perfil demográfico, estilo de vida, autopercepção negativa de saúde e uso dos serviços de saúde