National Institute of Health Dr. Ricardo Jorge
Repositório Científico do Instituto Nacional de SaúdeNot a member yet
9086 research outputs found
Sort by
Department of Human Genetics of INSA: 50 years of activity in diagnosis, prevention, and research of genetic disease in Portugal
No full textSafety evaluation of d‐α‐tocopheryl polyethylene glycol‐1000 succinate (Vitamin E TPGS) as a food additive
No full textThe EFSA Panel on Food Additives and Flavourings (FAF) provides a scientific opinion on the safety of d‐α‐tocopheryl polyethylene glycol‐1000 succinate (Vitamin E TPGS) as a new food additive to be used in several food categories as emulsifier. In 2007, the EFSA AFC Panel assessed TPGS as a source of tocopherol intended to be used in foods for particular nutritional uses. The Panel considered the AFC Panel assessment relevant for the present new food additive. Compositional data showed that the proposed food additive is composed of Vitamin E TPGS monoesters (< 82% w/w of the whole preparation) and diesters (<20% w/w of the whole preparation). Data on the hydrolysis of Vitamin E TPGS showed that the ester bond between d‐α‐tocopherol and succinic acid is stable under the tested conditions, as no increase in free d‐α‐tocopherol was observed. Vitamin E TPGS is poorly absorbed and does not represent a source of Vitamin E in the healthy population. Vitamin E TPGS does not raise a concern with respect to genotoxicity and no adverse effects on reproductive and developmental parameters were observed up to 1000 mg TPGS/kg bw per day, the highest dose tested and identified as a reference point. Due to the limitations in the available data (e.g. in reporting), the Panel decided to use an MOE approach instead of deriving an ADI. The Panel considered the calculated MOEs sufficient. Based on the available data, the Panel concluded that the use of Vitamin E TPGS as a new food additive does not raise a safety concern at the proposed use and use levels
Monitoring mortality in Portugal: evolution of all-cause mortality during 2024
No full textA monitorização da mortalidade por todas as causas é uma ferramenta útil na identificação de fenómenos de saúde, ou desastres de elevada magnitude ou gravidade e que podem, por isso, ter impacto na mortalidade. Este trabalho teve como objetivo descrever a evolução da mortalidade por todas as causas durante o ano de 2024 [semana 01/2024 à semana 52/2024 (01 janeiro de 2024 a 29 dezembro de 2024)], bem como, identificar e analisar os períodos de excesso de mortalidade. Foram analisados dados semanais de mortalidade, estratificados por sexo e grupo etário. A mortalidade esperada foi estimada através de modelos de regressão linear ajustados para tendências temporais e sazonalidade, excluindo-se os períodos associados a eventos com potencial impacto na mortalidade. A identificação dos períodos de excesso de mortalidade baseou-se na aplicação de regras de Westgard, e os excessos foram quantificados em termos absolutos e relativos. No período em estudo, foram registados 118.360 óbitos em Portugal, tendo sido identificados dois períodos de excesso de mortalidade a nível nacional [3.072 óbitos em excesso (IC 95%: 2.534-3.610)]. Foram estimados excessos de mortalidade nos grupos etários acima dos 45 anos, observando-se um gradiente crescente com a idade. Pela coincidência temporal podemos concluir que os períodos de excesso de mortalidade terão estado potencialmente associados à epidemia de gripe, ao período de maior circulação de COVID-19, e ao período de calor extremo ocorrido em 2024.All-cause mortality monitoring is a useful tool for identifying health events or disasters of high severity or high incidence in the population, which have impact on mortality. The aim of this work was to describe the evolution of all-cause mor tality during 2024 [week 01/2024 to week 52/2024 (01 January 2024 to 29 December 2024)], as well as to identify and analyse the periods of excess mortality. Weekly mortality data was analysed, stratified by sex and age group. Expected mortality was estimated using linear regression models adjusted for time trends and seasonality, excluding periods associated with events with a potential impact on mortality. The identification of periods of excess mortality was based on the application of Westgard rules, absolute and relative excess mor tality were estimated. During the study period, 118,360 deaths were registered in Portugal, and two periods of excess mortality were identified at national level [3,072 excess deaths (95% CI: 2,534-3,610)]. Excess mortality was observed in age groups over 45 years, with an increasing gradient with age. Due to the coincidence in time, we might conclude the periods of excess mortality were potentially associated with the flu epidemic, the period of highest circulation of COVID-19, and the period of extreme heat occurred in 2024
A atividade do Instituto Nacional de Saúde Doutor Ricardo Jorge à luz dos Objetivos do Desenvolvimento Sustentável [Editorial]
No full textAo percorrer os 15 artigos incluídos neste trigésimo oitavo número do Boletim Epidemiológico Observações do Instituto Nacional de Saúde Doutor Ricardo Jorge (INSA), podemos, adotando uma interpretação lata da Agenda 2030 preconizada pela Organização Mundial da Saúde (OMS), associar, diretamente ou indiretamente, dez daqueles artigos ao terceiro Objetivo do Desenvolvimento Sustentável (ODS 3: Garantir o acesso à saúde de qualidade e promover o bem-estar para todos, em todas as idades), constatação natural num Instituto público do sector da saúde como INSA. (...
Probe-based metagenomic pathogen detection: advancing laboratory capacity for complex diagnosis
No full textThis article is part of the Research Topic: Rapid and Efficient Analytical Technologies for Pathogen DetectionProbe-based pathogen enrichment, followed by NGS, is a promising tool for complex diagnosis, overcoming traditional challenges of shotgun metagenomics, namely small microbial/human genetic material ratio and demanding computational resources. Here, we assessed the combined detection performance of two Illumina probe-based panels, the Respiratory and the Urinary Pathogen ID panels (RPIP and UPIP), using 99 clinical samples of 15 different matrices (e.g., cerebrospinal fluid, plasma, serum, urine, swabs, biopsies, etc.) available from Portuguese National Reference Laboratories. This sample set involved 114 "PCR-positive hits" (Ct values range of 9.7-41.3; median of 28.4) for 52 non-redundant human pathogens. For a more detailed bioinformatics assessment, as a complement of the Illumina turnkey solution (Explify), we applied an extended version of our INSaFLU-TELEVIR(+) metagenomics pipeline. Whereas Explify analyses resulted in an initial detection frequency of 73.7% (84/114), the subsequent application of INSaFLU-TELEVIR(+), including taxonomic classification followed by confirmatory read mapping, enabled an overall detection proportion of 79.8% (91/114) of the PCR-positive hits. This translated into a detection rate increment from 54.3% (19/35) to 65.7% (23/35) for bacteria, and from 85.3% (58/68) to 89.7% (61/68) for viruses. The implemented workflow was also very satisfactory for samples with qPCR Ct values above 30, with an overall detection frequency of 71.8% (28/39) when compared with the 92.0% (46/50) observed for those with Ct ≤ 30. In summary, this study validated and established a pioneering approach at the Portuguese National Institute of Health to support clinicians in complex diagnosis, contributing to advance diagnostic capabilities toward a more informed clinical decision and potential improvement of infectious disease outcomes.This study was co-funded by the European Union project “Sustainable use and integration of enhanced infrastructure into routine genome-based surveillance and outbreak investigation activities in Portugal” - GENEO (Project No. 101113460) on behalf of the EU4H programme (EU4H-2022-DGA-MS-IBA-01-02). This study was also co-financed through the DURABLE project. The DURABLE project has been co-funded by the European Union, under the EU Health Programme (EU4H), Project No. 101102733. Neither the European Union nor the granting authority can be held responsible for them. The acquisition of WGS-associated equipment used in this study was co-funded by the Health Emergency Preparedness and Response (HERA) grant “Grant/2021/PHF/23776” and the GenomePT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020 – Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by the Portuguese Science and Technology Foundation (FCT). We also thank the Infraestrutura Nacional de Computação Distribuída (INCD) for providing computational resources for INSaFLU-TELEVIR testing. INCD was funded by FCT and FEDER under project 22153-01/SAICT/2016
Transcriptomic screen for DIS3, DIS3L1 and DIS3L2-associated functional networks in colorectal cancer
No full textThe final step of cytoplasmic mRNA degradation proceeds in either a 5’-3’ direction, catalyzed by XRN1, or in a 3’-5’ direction catalyzed by the exosome and DIS3L2. In yeast, DIS3/Rrp44 protein is the catalytic subunit of the exosome. In humans, there are three known paralogues of this enzyme: DIS3, DIS3L1, and DIS3L2. Important findings over the last years have shed a new light onto the mechanistic details of RNA degradation by these exoribonucleases. In addition, it has been shown that they are involved in growth, mitotic control and important human diseases, including cancer. For example, DIS3L2 inactivation was associated with mitotic abnormalities and altered expression of mitotic checkpoint proteins (1). In another study, DIS3 was found to be highly expressed in colorectal cancer (CRC), suggesting an oncogenic function (2).
A major challenge in systems biology is to reveal the cellular networks that give rise to specific phenotypes (3). In this project, we aim to analyze how DIS3, DIS3L1 and DIS3L2 regulate the human transcriptome, and how their functional interactions modulate the transcriptional reprogramming of colorectal cancer cells.
In order to unveil the role of these exoribonucleases in general mRNA decay, and/or in cytoplasmic mRNA surveillance mechanisms, such as nonstop- and nonsense-mediated decay (NSD and NMD), we performed their knockdown and measured the mRNA levels of various reporter transcripts (endogenous and exogenous), with emphasis in natural NMD targets.
Our results show that DIS3 and DIS3L1 seem to be involved in the normal mRNA turnover, as well as in the NSD and NMD mechanisms. However, some natural NMD targets are resistant to these nucleases. On the other hand, DIS3L2 is not involved in the normal mRNA turnover or in NSD, being specifically involved in the degradation of some NMD targets. Presently, we are interested in identifying the transcript features implicated in the decision-making process of DIS3L2-mediated decay of natural NMD targets, as well as the corresponding mechanism. With this purpose, we performed a bioinformatics analysis of available transcriptomic data from DIS3, DIS3L1, DIS3L2+XRN1, XRN1, or UPF1 (a central player in NMD) knockdown experiments and identified transcripts differentially expressed in each condition. Results show some, but not total, redundancy between the upregulated transcripts, and this supports our experimental data.N/
Molecular genetic diagnosis of hereditary breast and ovarian cancer and colorectal cancer syndromes: experience from the Department of Human Genetics of INSA (1994-2025)
No full textInfeção por VIH em Portugal – 2025
No full textRelatório anual Infeção VIH em Portugal – 2025. Este relatório conjunto DGS/INSA apresenta os dados mais recentes da vigilância epidemiológica da infeção por VIH em Portugal, bem como resultantes de iniciativas de prevenção e rastreio desenvolvidas no âmbito do Programa Nacional para as Infeções Sexualmente Transmissíveis e Infeção pelo VIH (PNISTVIH).
Dos resultados e conclusões apresentados no documento, destaca-se o seguinte:
(1) Vigilância epidemiológica: - Em Portugal, segundo os dados recolhidos a 30 de junho de 2025, foram notificados 997 casos de infeção por VIH com diagnóstico em 2024, dos quais 951 com diagnóstico em Portugal; - Registou-se uma redução de 35% no número de novos casos de infeção por VIH e de 43% em novos casos de SIDA entre 2015 e 2024; - A maioria (72,3%) dos novos casos de infeção VIH em adolescentes e adultos (≥ 15 anos) registou-se em homens. A taxa de novos diagnósticos mais elevada registou-se no grupo etário dos 25-29 anos (28,5 casos/105 habitantes) e em 25,2% dos novos casos a idade ao diagnóstico foi igual ou superior a 50 anos. Foram notificados 3 casos de infeção VIH em crianças com idade <15 anos; - A transmissão heterossexual mantém-se como a mais frequente (52,5%), mas os casos em homens que têm sexo com homens (HSH) corresponderam à maioria dos novos diagnósticos em homens (60,6%); - Apresentaram-se tardiamente aos cuidados de saúde 53,9% das pessoas com novo diagnóstico de VIH e 65,4% das pessoas com 50 ou mais anos; - Foram comunicados 194 casos de SIDA com diagnóstico do estádio em 2024 e 108 óbitos em pessoas que viviam com VIH. Em 46,3% dos óbitos o diagnóstico VIH tinha ocorrido há mais de 20 anos; - Em Portugal, ao longo das quatro décadas da epidemia VIH, foram diagnosticados 66 421 casos de infeção por VIH, 23 946 atingiram o estádio de SIDA e foram notificados 16 080 óbitos. Estima-se que viviam em Portugal, em 2023, 49 699 pessoas com infeção por VIH (PVVIH), 94,2% destas já diagnosticadas; - Foi possível obter dados completos do "continuum of care" de 26 hospitais nacionais, relativos a 36 184 PVVIH, constatando-se que 97,8% estavam em tratamento e, destas, 95,9% atingiram a supressão virológica; - O relatório apresenta ainda uma análise das causas de morte reportadas nos certificados dos óbitos de pessoas que viviam com VIH, constatando-se que desde 2021 predominam as causas de morte não associadas à infeção por VIH; - São também apresentadas as características dos casos com diagnóstico entre 2014 e 2023 e residência nas 12 cidades portuguesas que aderiram à iniciativa Fast-track cities. As estimativas realizadas revelaram que em cinco destas cidades mais de 95% das PVVIH que conheciam a sua infeção.
(2) Prevenção, rastreio e estigma: - O PNISTVIH prosseguiu e/ou monitorizou as atividades referentes à prevenção da infeção por VIH efetuadas em 2024, com destaque para a distribuição de materiais preventivos, o Programa de Troca de Seringas, a profilaxia pré-exposição ao VIH (PrEP) e a profilaxia pós-exposição (PPE). É apresentado um balanço positivo, tendo aumentado significativamente o número de pessoas que tiveram acesso à PrEP, incluindo fora do contexto hospitalar. O número de testes de rastreio e diagnóstico para VIH realizados no país, em diferentes contextos, mostrou um ligeiro decréscimo face aos anos precedentes
RSV-Bacterial Co-Infection Is Associated With Increased Illness Severity in Hospitalized Children - Results From a Prospective Sentinel Surveillance Study
No full textDuring the autumn/winter respiratory syncytial virus (RSV) epidemics, bacterial co-infection is common and affects the disease severity. We aimed to understand the relationship between RSV-bacterial co-infections and clinical severity since the RSV seasonality change after COVID-19 pandemic. We conducted a prospective, sentinel surveillance study at 20 sites in Portugal in children under 2 years hospitalized with RSV, between April 21 and January 23. Effect of co-infection with potentially pathogenic bacteria (PPB) on the length of hospitalization and disease severity was investigated using multivariate linear and log-binomial regression models. Among 678 RSV hospitalizations, 67.4% occurred in children under 6 months and 15.3% in preterm; 20.4% tested positive for PPB; median length of hospitalization was 5 days (IQR: 3-7days). Children coinfected with PPB had a higher rate of ICU admission (29.7% vs. 3.5%, p < 0.001), resulting in more prolonged hospitalizations (7 vs. 5 days, p < 0.001) and a 13-fold risk of having severe disease (RR: 13.2, 95% CI:7.3-23.9). RSV-bacterial co-infection was associated with increased length of hospitalization and severe illness during off-season epidemics. This risk is probably overestimated, as laboratory testing for bacterial infections is usually higher in severely ill-appearing children. Measures to prevent outgrowth of pathogenic bacteria within the respiratory tract should be discussed
Safety evaluation of pea fibre concentrate (FIPEA) as food additive
No full textThe EFSA Panel on Food Additive and Flavourings (FAF Panel) provides a scientific opinion on the safety assessment of the proposed use of pea fibre concentrate (FIPEA) as a food additive. FIPEA is a powder consisting mainly of dietary fibres (i.e. pectin and hemicellulose), and low amounts of protein, derived from yellow pea (P. sativum). The manufacturing process includes extensive heat treatments, (e.g. > 100°C for more than 40 min), conditions which lead to inactivation of lectins, that in FIPEA do not pose a safety concern. A specific α‐amylase is used in the manufacturing, and this should be included in the definition of the proposed specifications. The Panel considered that the additional contribution of FIPEA to the total fibre intake in adults and toddlers would be acceptable considering the levels that are considered adequate by the NDA Panel. The Panel recommended to lower the specification limits proposed for the toxic elements. The solubility test indicates that the material does not require specific assessment at the nanoscale. No toxicological data have been submitted on FIPEA. The Panel considered that, similarly to water‐soluble soybean polysaccharides, FIPEA is not absorbed intact but undergoes extensive fermentation by the intestinal microbiota in humans and is not of genotoxic concern. Dry peas (raw material) are a staple food, with a very long history of safe use in the EU. FIPEA is extracted with hot water from the insoluble fibrous material of dehulled yellow peas, therefore the structure of the fibres is not chemically modified, and no new by‐products or components of toxicological concern are expected from the manufacturing process. The Panel concluded that there was no need for a numerical acceptable daily intake (ADI) and that pea fibre concentrate (FIPEA) as a new food additive does not raise a safety concern at the proposed use and use levels