National Institute of Health Dr. Ricardo Jorge
Repositório Científico do Instituto Nacional de SaúdeNot a member yet
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Ribonucleases and nonsense-mediated decay (NMD): An unexpected role for DIS3L2 over human NMD targets
No full textBackground: The nonsense-mediated mRNA decay (NMD) pathway selectively degrades mRNAs carrying a premature translation-termination codon but also regulates the abundance of a large number of physiological RNAs that encode full-length proteins. In human cells, NMD-targeted mRNAs are degraded by endonucleolytic cleavage and exonucleolytic degradation from both 5’ and 3’ ends. This is done by a process not yet completely understood that recruits decapping and 5’-to-3’ exonuclease activities, as well as deadenylating and 3’-to-5’ exonuclease exosome activities. In yeast, DIS3/Rrp44 protein is the catalytic subunit of the exosome, but in humans, there are three known paralogues of this enzyme: DIS3, DIS3L1, and DIS3L2. However, DIS3L2 exoribonuclease activity is independent of the exosome. DIS3L1 and DIS3L2 exoribonucleases localize in the same compartment where NMD occurs, however nothing is known about their role in this process. In order to unveil the role of DIS3L2 in NMD, we performed its knockdown in HeLa cells and measured the mRNA levels of various natural NMD targets. Our results show that some NMD targets are highly stabilized in DIS3L2-depleted cells. In addition, mRNA half-life analysis indicated that these NMD targets are in fact direct DIS3L2 substrates. We also observed that DIS3L2-mediated decay depends on the activity of the terminal uridylyl transferases (TUTases) Zcchc6/11 (TUT7/4). Together, our findings establish the role of DIS3L2 and uridylation in NMD.PJC is recipient of a fellowship from BioSys PhD programme (Ref: SFRH/BD/52495/2014) from Fundação
para a Ciência e aTecnologia (FCT).
Work partially supported by UID/MULTI/04046/2013 centre grant from FCT, Portugal (to BioISI) and Instituto
Nacional de Saúde, Dr Ricardo Jorge (INSA), PortugalN/
Impacts of a changing earth on microbial dynamics and human health risks in the continuum between beach water and sand
No full textAlthough infectious disease risk from recreational exposure to waterborne pathogens has been an active area of research for decades, beach sand is a relatively unexplored habitat for the persistence of pathogens and fecal indicator bacteria (FIB). Beach sand, biofilms, and water all present unique advantages and challenges to pathogen introduction, growth, and persistence. These dynamics are further complicated by continuous exchange between sand and water habitats. Models of FIB and pathogen fate and transport at beaches can help predict the risk of infectious disease from beach use, but knowledge gaps with respect to decay and growth rates of pathogens in beach habitats impede robust modeling. Climatic variability adds further complexity to predictive modeling because extreme weather events, warming water, and sea level change may increase human exposure to waterborne pathogens and alter relationships between FIB and pathogens. In addition, population growth and urbanization will exacerbate contamination events and increase the potential for human exposure. The cumulative effects of anthropogenic changes will alter microbial population dynamics in beach habitats and the assumptions and relationships used in quantitative microbial risk assessment (QMRA) and process-based models. Here, we review our current understanding of microbial populations and transport dynamics across the sand-water continuum at beaches, how these dynamics can be modeled, and how global change factors (e.g., climate and land use) should be integrated into more accurate beachscape-based models.E.M.S. was supported by the U.S. National Science Foundation (U.S. NSF), grant OCE-1566562.
Financial support from CESAM (UID/AMB/50017-POCI-01-0145-FEDER-007638), via FCT/MCTES, from national funds (PIDDAC), cofunded by FEDER, (PT2020 Partnership Agreement and Compete 2020).info:eu-repo/semantics/publishedVersio
Genetic variants in the IFNGR2 locus associated with severe chronic Q fever
No full textQ fever is a highly contagious zoonosis capable of causing large outbreaks of important health and economic consequences. Host genetic factors are believed to influence the development of severe chronic Q fever following the infection by the etiological agent, Coxiella burnetii. Targetted next generation sequencing (NGS) was performed in a case-control genetic association study on 53 confirmed Q fever cases, including 38 compatible with acute and 15 with chronic disease, and 29 samples from the general Portuguese population. Four SNPs in the IFNGR2 locus, rs78407108 G > A, rs17879956 C > T, rs7277167 C > T, and rs9974603 C > A, showed a statistically significant association to chronic Q fever, resisting the Bonferroni correction. These belonged to haplotypes significantly associated with chronic Q fever. The individual SNPs are referenced in the GTEx database as possible eQTLs. Given the direct bearing of IFNGR2 on IFN-γ signaling, the possible involvement of the associated variants with higher IFNGR2 expression could be in line with observations suggesting that IFN-γ production in chronic Q fever patients is significantly higher than in healthy controls. Further investigations are required to clarify the role of IFNGR2 signaling in association with chronic Q fever
Comparative analysis of the nutritional quality of plant-based processed foods and animal-origin counterparts in the Portuguese and UK markets
No full textThe increasing demand for healthier and more sustainable foods has led to the rise of plant-based processed foods that serve as alternatives to animal-origin products. While plant-based diets are often considered healthful, these products frequently present nutritional limitations. This study aimed to compare the nutritional composition and quality of plant-based and animal-origin processed foods available in the Portuguese and UK markets. A total of 1170 plant-based and 2452 animal-origin counterparts were analysed, using two reference frameworks: the Portuguese Integrated Strategy for the Promotion of Healthy Eating (EIPAS) and the Directorate-General for Health (DGS) Label Decoder reference values. Findings indicated that 92.9 % of plant-based foods in Portugal, and 95.4 % in UK, exceeded EIPAS sugar and salt limits (evaluated together), suggesting that the perceived health benefits may not be aligned with their nutritional content. Compliance with EIPAS varied significantly by food type, for each country. Plant-based alternatives often had higher energy, carbohydrates, and fibre, but lower levels of saturates and protein compared to their counterparts. According to the DGS Label Decoder, 17.7 %, 18.1 %, and 29.0 % of plant-based alternatives in PT market, and 18.4 %, 22.6 %, and 26.7 % in UK market, had high levels of fat, saturates, and salt, respectively. These findings underscores that, despite the perceived health benefits of plant-based foods, not all present a balanced and healthy nutritional profile. Additionally, this study highlights significant nutritional variability across plant-based alternatives and markets. This reinforces the need for informed consumer choices, better product formulations, and public health actions to improve their nutritional quality.Highlights: -Salt exceeded 0.3 g/100 g in over 95 % of meat and fish imitates in both markets; -Sugar exceeded 5 g/100 g in over 48 %/23 % of dairy alternatives in PT/UK markets. -29/27 % of PT/UK plant-based processed foods assessed were high in salt. -18/23 % of PT/UK plant-based processed foods assessed were high in saturates. -Plant-based alternatives need better nutritional profiles for healthier patterns
Assessment of urinary iodine concentration in school-aged children (6 to 12 years) in Cape Verde
No full textO Instituto Nacional de Saúde Doutor Ricardo Jorge (INSA) e o Instituto Nacional de Saúde Pública de Cabo Verde (INSP) estabeleceram um protocolo de colaboração para realizarem a avaliação e monitorização do iodo urinário em crianças de Cabo Verde. Assim, o INSP selecionou crianças das nove ilhas habitadas (Santo Antão, São Vicente, São Nicolau, Sal, Boa Vista, Maio, Santiago, Fogo e Brava) e realizou a recolha de amostras de urina de 24 horas de 541 crianças dos 6 aos 12 anos, que posteriormente foram enviadas para o INSA para determinação do teor de iodo por espectrometria de massa com plasma indutivo acoplado (ICP-MS).
Os resultados revelaram uma mediana de 155 μg/L nas iodúrias da população em estudo e um aporte de iodo considerado adequado para apenas 36 % das crianças. É necessária especial atenção para a existência de muitos casos de excesso de iodo nas ilhas de Santo Antão, São Nicolau e Sal e casos de deficiência nas ilhas de São Vicente, Boa Vista e Fogo.
Este estudo revelou a importância da monitorização da implementação de políticas públicas direcionadas para a correção de situações consideradas inadequadas para uma vida mais saudável em termos da ingestão de iodo.The National Institute of Health Doctor Ricardo Jorge (INSA) and the National Institute of Public Health of Cape Verde (INSP) have established a collaborative protocol to assess and monitor urinar y iodine levels in children throughout Cape Verde. INSP selected children from the nine inhabited islands (Santo Antão, São Vicente, São Nicolau, Sal, Boa Vista, Maio, Santiago, Fogo, and Brava) and collected 24-hour urine samples from 541 children aged 6 to 12 years, which were subsequently sent to INSA for iodine content determination via Inductively Coupled Plasma Mass Spectrometr y (ICP-MS).
The results revealed a median of 155 μg/L in the iodine levels of the study population and an iodine intake considered adequate for only 36% of the children. At tention must be given to the numerous cases of excess iodine on the islands of Santo Antão, São Nicolau, and Sal, as well as the instances of deficiency on the islands of São Vicente, Boa Vista, and Fogo. This study highlighted the importance of monitoring the implementation of public policies, with a focus on improving situations considered inadequate for a healthier life in terms of iodine intake
External quality assessment in prenatal diagnosis of chromosomal anomalies within the Cytogenetics Unit of INSA – 30 years of evolution (1994-2024)
No full textSecond tier tests for neonatal screening of congenital adrenal hyperplasia
No full textO rastreio neonatal tem um papel essencial na deteção precoce da Hiperplasia Congénita das Suprarrenais, numa fase pré-sintomática, permitindo uma institucionalização atempada de tratamento com melhoras no curso clínico do recém-nascido. O marcador utilizado para efeitos de rastreio neonatal, é a 17-α-hidroxiprogesterona (17-OHP), quantificada em cartão de Guthrie por fluoroimunoensaio. No entanto, este marcador origina classicamente um elevado número de falsos positivos, sobretudo em recém-nascidos de baixo peso e/ou prematuros. De forma a contornar esta limitação, a estratégia preconizada passa pelo ajuste dos valores de referência da 17-OHP, em função do peso e/ou idade gestacional e a utilização de provas de segundo nível, através da análise de perfis de esteroides, em sangue em papel. Neste trabalho foi levada a cabo a definição de valores de referência para a 17-OHP (estratificados por peso e idade gestacional) adaptados à população portuguesa de recém-nascidos e foram implementadas as provas de segundo nível. Da conjugação destas duas estratégias, resulta uma abordagem que se traduzirá numa considerável melhoria de sensibilidade e especificidade, caso se considere no futuro a introdução do rastreio desta patologia no Programa Nacional de Rastreio Neonatal.Neonatal screening has an essential role in the early detection of Congenital Adrenal Hyperplasia in a pre-symptomatic phase, allowing an early institutionalization of treatment with improvements in the clinical course of the newborn. The marker used for neonatal screening purposes is 17-α-hydroxyprogesterone (17-OHP), quantified in Guthrie cards by fluoroimmunoassay. However, this marker classically leads to a high number of false positives, especially in low birth weight and/or premature newborns. To overcome this limitation, various screening programs resort to the adjustment of the reference values of 17-OHP, according to weight and/or gestational age and the use of second-tier tests, through the analysis of steroid profiles, in dried blood spots. In this work, the definition of reference values for 17-OHP (stratified by weight and gestational age) adapted to the Portuguese population of newborns was carried out and the second-tier tests were implemented. The combination of stratified reference values and the use of these second-tier tests results in an approach that will translate into a considerable improvement in sensitivity and specificity, if the introduction of screening for this pathology in the National Neonatal Screening Program is considered in the future
Safety assessment of the process NGR LSP used to recycle post‐consumer PET into food contact materials
No full textMaria João Silva. Departamento de Genética Humana, INSAThe EFSA Panel on Food Contact Materials (FCM) assessed the safety of the recycling process NGR LSP (EU register number RECYC328). The input is hot washed and dried poly(ethylene terephthalate) (PET) flakes mainly originating from collected post‐consumer PET containers, with no more than 5% PET from non‐food consumer applications. The flakes are dried (step 2), melted in an extruder (step 3) and decontaminated during a melt‐state polycondensation step under high temperature and vacuum (step 4). In step 5, the material is granulated. Having examined the challenge test provided, the Panel concluded that the melt‐state polycondensation (step 4) is critical in determining the decontamination efficiency of the process. The operating parameters to control the performance of step 4 are the pressure, the temperature, the residence time and the characteristics of the reactor. It was demonstrated that this recycling process ensures that the level of migration of potential unknown contaminants into food is below the conservatively modelled migration of 0.0481 or 0.0962 μg/kg food, depending on the molar mass of a contaminant substance. Therefore, the Panel concluded that the recycled PET obtained from this process is not of safety concern, when used at up to 100% for the manufacture of materials and articles for contact with all types of foodstuffs, including drinking water, for long‐term storage at room temperature or below, with or without hot‐fill. Articles made of this recycled PET are not intended to be used in microwave and conventional ovens and such uses are not covered by this evaluation
Neurometabolic profiles of autism spectrum disorder patients with genetic variants in specific neurotransmission and synaptic genes
No full textAutism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by impaired social interaction, and restricted and repetitive patterns of behavior. ASD presents as a clinical spectrum, with variable levels of severity and multiple co-occurring conditions. The etiology of ASD may involve hundreds of genes and there is evidence that neurotransmitter and synaptic (NS) pathways are implicated. Proton Magnetic Resonance Spectroscopy (H-MRS) has made it possible to study the concentration of brain neurometabolites and compare their levels in the brains of ASD and control individuals. We integrated genetic variants in NS genes with H-MRS analysis, and identified 12 predicted damaging variants (PDVs) in 12 NS genes in 10 ASD individuals, most mapping to genes involved in Gamma-aminobutyric acid (GABA) and glutamate pathways. Total creatine (tCr) and total N-acetyl aspartate (tNAA), markers of bioenergetics and neuronal metabolism, respectively, were lower in ASD patients with genetic alterations in NS genes compared to a control group without ASD. We conclude that PDVs in NS genes that are important for the regulation of glutamate or involved in GABAergic functions are associated with neurometabolic alterations, and that dysfunction in glutamatergic and/or GABAergic pathways may be implicated as these pathways are linked to the metabolic measures altered in cases.This research was funded by Fundação para a Ciência e a Tecnologia (FCT), Portugal, Centre grants to BioISI (DOI: https://doi.org/10.54499/UIDB/04046/2020, UIDP/04046/2020, UID/04046/2025), PAC-POCI-01-0145-FEDER-016428 MEDPERSYST and the National Institute of Health Doutor Ricardo Jorge. J.V., A.R.M. and J.X.S. are recipients of a fellowship from the BioSys PhD program PD65-2012 (J.V. Ref: PD/BD/131390/2017; A.R.M. Ref: PD/BD/113773/2015; and J.X.S. Ref: PD/BD/114386/2016) from Fundação para a Ciência e a Tecnologia (FCT), (Portugal). SM was funded under Fundação para a Ciência e a Tecnologia (Portugal) CEEC Grant ref 2022.00474.CEECIND/CP1714/CT0030(https://doi.org/10.54499/2022.00474.CEECIND/CP1714/CT0030)
Programa Nacional de Rastreio Neonatal: relatório 2024
No full textPresidente do PNRN: Fernando de Almeida, Presidente do Conselho Diretivo do INSA.Relatório de atividades do Programa Nacional de Rastreio Neonatal (PNRN) relativo ao ano de 2024, elaborado pela Comissão Executiva do Programa. O documento refere todos os casos detetados, bem como os Centros de Tratamento de apoio aos doentes e a prevalência ao nascimento das doenças rastreadas, entre outra informação estatística.
Do presente relatório de desenvolvimento do Programa, destaca-se o seguinte: - Em 2024, as 27 doenças integradas no painel do Programa Nacional de Rastreio Neonatal (Hipotiroidismo Congénito, Fibrose Quística, Drepanocitose (Anemia de Células Falciformes e 24 Doenças Hereditárias do Metabolismo) foram rastreadas de uma forma sistemática, em 84.631 recém-nascidos (RN) e identificados 118 doentes com uma média de idade de início de tratamento de 9,5 dias de vida; - Em 2022, teve início o estudo-piloto para o rastreio neonatal da Atrofia Muscular Espinal, que foi concluído no final de 2024 com uma prevalência ao nascimento de 1:15.520 e foi proposta a sua integração no painel das doenças rastreadas; - A taxa de cobertura nacional mantém-se próxima dos 100%, o que constitui um excelente indicador de aceitação da população a este programa nacional de saúde pública; - Desde o início do Programa, foram rastreados 4.309.181 recém-nascidos e identificados 2.796 casos positivos; - Pela qualidade dos seus indicadores, número de patologias rastreadas, tempo médio de início de tratamento e taxa de cobertura a nível nacional, considera-se que é, de facto, um Programa de grande eficácia clínica e epidemiológica.
Criado em 1979, este programa de saúde pública, conhecido como “teste do pezinho”, tem como objetivo primário o rastreio neonatal de doenças raras, de forma a evitar a evolução da patologia rastreada, através do diagnóstico pré-sintomático e da orientação para implementação precoce de terapia adequada.
A Unidade de Rastreio Neonatal, Metabolismo e Genética do DGH, que funciona no Centro de Saúde Pública Doutor Gonçalves Ferreira do INSA no Porto, é o braço laboratorial do Programa, sendo composta pelo Laboratório Nacional de Rastreios, Laboratório de Metabolismo e Laboratório de Genética Molecular.
Após 45 anos de atividade, o PNRN continua a apresentar um elevado padrão de qualidade e desenvolvimento que lhe confere um prestígio nacional e internacional por todos reconhecido e respeitado, mantendo uma trajetória e um dinamismo de que são sinais, para além dos indicadores de eficácia clínica e epidemiológica, o elevado nível de produção científica, a implementação de normas internacionais de qualidade e o alargamento do rastreio a novas entidades nosológicas