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- Estudos Funcionais de Variantes no Gene APOB em Doentes com Diagnóstico Clínico de Hipercolesterolemia FamiliarPublication . Ramos, Diana Catarina Fernandes; Bourbon, Mafalda; Alves, Ana CatarinaA hipercolesterolemia familiar (FH) é uma doença caracterizada por níveis elevados de colesterol LDL, que se acumulam nas artérias, promovendo o desenvolvimento precoce de eventos cardiovasculares. Geneticamente, a FH é transmitida de forma autossómica semi-dominante, sendo causada por variantes nos genes LDLR, APOB e PCSK9. As variantes no gene APOB afetam a ligação do colesterol LDL ao seu recetor, representando 5 a 10% dos casos de FH. No entanto, para a maioria das variantes identificadas, o efeito funcional na proteína ainda não está determinado. Esta dissertação teve como objetivo principal investigar a correlação entre fenótipo e genótipo, além de caracterizar funcionalmente variantes identificadas no gene APOB em indivíduos com diagnóstico clínico de FH na população portuguesa. Como objetivo secundário, foi desenvolvida uma base de dados que reúne todas as variantes deste gene com estudos funcionais realizados até ao momento. A identificação das variantes foi realizada por sequenciação de nova geração (NGS) e confirmada por PCR e sequenciação de Sanger, seguida da pesquisa da variante nos familiares dos casos index. As variantes em estudo foram identificadas no âmbito do projeto EPHF. O LDL dos participantes foi isolado por ultracentrifugação a partir do soro de casos index e familiares com variantes no gene APOB, bem como de indivíduos normolipidémicos. Este LDL foi marcado com fluorescência e incubado em células CHO-ldlΔ7 para avaliar a capacidade de ligação e internalização do LDL. A caracterização funcional, realizada por citometria de fluxo com LDL fluorescente, revelou que as variantes p.(Asp1456Asn), p.(Val4295Leu) e p.(Arg4519Thr) apresentavam ligação e internalização normais do LDL, indicando que estas variantes não comprometem a função da proteína. Este trabalho destaca a importância de caracterizar funcionalmente as variantes no gene APOB para melhorar o diagnóstico dos indivíduos com FH, possibilitando tratamentos mais adequados a cada caso e contribuindo para a redução do risco cardiovascular.
- COVID-19 Vaccine Effectiveness Against Medically Attended Symptomatic SARS-CoV-2 Infection Among Target Groups in Europe, October 2024-January 2025, VEBIS Primary Care NetworkPublication . Delaunay, Charlotte Laniece; Verdasca, Nuno; Monge, Susana; Domegan, Lisa; Sève, Noémie; Buda, Silke; Meijer, Adam; Lucaccioni, Héloïse; Torrijos, Miriam López; McKenna, Adele; Enouf, Vincent; Dürrwald, Ralf; In't Velt, Eline; Laiglesia, Mª Ángel de Valcárcel; Bennett, Charlene; Masse, Shirley; Erdwiens, Annika; Hooiveld, Mariette; Mlinarić, Ivan; Túri, Gergő; Rodrigues, Ana Paula; Martínez-Baz, Iván; Lazar, Mihaela; Latorre-Margalef, Neus; Borges, Vitor; Kaczmarek, Marlena; Bacci, Sabrina; Kissling, Esther; European primary care VE groupWe estimated the effectiveness of 2024/25 COVID-19 vaccination against medically attended SARS-CoV-2 infection in Europe, among target groups. We included 3204 patients (8/139 cases vaccinated: 6%; 517/3065 controls vaccinated: 17%) from a multicentre, test-negative design study at primary care level. Vaccine effectiveness was 66% (95% CI: 34-85) overall, 73% (95% CI: 21-94) and 54% (95% CI: -3 to 83) in the first and second months post-vaccination, respectively. Overall vaccine effectiveness was 67% (95% CI: 33-86) among older adults (≥ 60 or ≥ 65 years). This relatively high COVID-19 VE (compared with previous seasons), as well as trends by time since vaccination, should be confirmed with additional data, as sample size was low.
- Conhecer a epidemiologia da infeção por vírus da imunodeficiência humana tipo 2 (VIH-2) em indivíduos residentes em Portugal: o que mudou nas últimas décadas?Publication . Mendes, Inês Filipa Santos; Pádua, Elizabeth; Piedade, JoãoThe main objectives of this study were to analyse the epidemiological evolution of HIV-2 infection in Portugal using demographic, clinical and laboratory data corresponding to samples from HIV-2-infected parturients received at INSA, and to conduct the molecular characterisation of HIV-2 in a convenience sample, focusing on the phylogenetic classification of viruses and identification of resistance mutations. The analysis of the overall sample received at the laboratory between 2006 and 2023 was based on known demographic and clinical data. The molecular analysis of HIV-2 was performed on selected samples, subjected to DNA extraction, nested-PCR amplification of the PR-RT and IN regions of the pol gene and the amplified samples sequenced by the Sanger method. The results obtained were discovered with several bioinformatics programs, the respective phylogenetic trees were constructed and the search for resistance mutations was carried out with available international databases. An analysis of data from samples of the total population (n=183) revealed that 16.6% of the parturients infected with HIV-2 were Portuguese, but there was a clear predominance of women born in Africa (83.4%), mostly in Guinea-Bissau and in the age group of 30-39 years. Between 2006 and 2023, an apparent general improvement in the immunological situation was observed, with an increase in the proportion of women with CD4+ T cells above 500 cells/μL and an increase in the rate of adherence to ART during pregnancy (56.2% to 64.0%), which was higher among African women (69.6%) compared to Portuguese women (66.7%). Over time, a transition from ART regimens containing only NRTI to NRTI regimens combined with INSTI was achieved, and between 2018 and 2023, this regimen was prescribed to 56.5% of parturients. The analysis of the selected convenience sample (n=99) proved to be representative of the total samples received in the laboratory between 2011 and 2023, for the demographic and clinical variations analysed. Amplification was successful in 48.5% of the samples for PR-RT and 46.5% of the samples for IN, with all sequences phylogenetically in HIV-2 group A and excluded of cluster A2. It was observed that 12 sequences derived from samples of 12 women presented mutations of interest, namely, in 7 of 45 sequences of the RT group and in 5 of 35 sequences of the IN group. Three sequences from each group presented accessory mutations associated with a possible reduction in susceptibility to antiretrovirals (I75V, V111I and F214L in RT and I84V, A153S in IN). However, resistance mutations were identified in 4 RT sequences and 2 IN sequences (K70R, Q151M, M184V and S215Y in RT and R263K and N155H in IN). This study revealed the need for greater efforts to implement measures to increase adherence to ART, as well as screening for HIV-2 infection, to prevent transmission and improve clinical outcomes in patients. The results produced in this study may contribute to updating knowledge about the epidemiological and molecular characteristics of HIV-2 in Portugal, as well as evidence of the existence of resistance mutations with an impact on the treatment of the infection.
- Porque e como monitorizar a ingestão de aditivos alimentaresPublication . Fernandes, PauloComunicação no âmbito da apresentação da metodologia e ods mais recentes dados sobre a ingestão de aditivos alimentares, pela população escolar entre os 11 e 17 anos, em Portugal Continental e reforçar a importância da sua monitorização sistemática, contribuindo para a proteção da saúde pública e para a confiança dos consumidores.
- Resultados da monitorização em Portugal (2024)Publication . Vasco, ElsaResultados da monitorização da ingestão de aditivos alimentares em Portugal (2024) em indivíduos dos 11 aos 17 anos de idade, no âmbito do projeto MONITADITIVOS. Objetivo geral: Avaliação da ingestão de aditivos alimentares em indivíduos dos 11 aos 17 anos de idade. Objetivos específicos: (OE) 1 Avaliação do consumo alimentar através de questionários às 24 horas anteriores; 2 Cálculo da Ingestão Diária Estimada (por indivíduo dos aditivos alimentares com base no consumo e nos Teores Máximos Permitidos (TMP); 3 Caracterização da ingestão por comparação da IDE com a respetiva Dose Diária Admissível (DDA) e eventual identificação dos aditivos alimentares que passam à fase seguinte de avaliação.
- Functional Studies in LDLR to Improve Genetic Diagnosis in Familial HypercholesterolemiaPublication . Alves, Ana Catarina; Graça, Rafael; Ferreira, Maria Simões; Correia, Bernardo Amaro; Medeiros, Ana Margarida; Miranda, Beatriz; Chora, Joana Rita; Bourbon, MafaldaFamilial hypercholesterolemia (FH) is the most common inherited disorder of lipid metabolism, affecting approximately 1 in 300 individuals. FH is an autosomal semidominant disorder and was the first genetic lipid metabolism disorder to be molecularly characterized. Individuals with FH present elevated blood cholesterol levels from birth, leading to a high cumulative risk of developing cardiovascular disease. Pathogenic variants in the low-density lipoprotein receptor (LDLR) gene are the primary cause of FH, with more than 4,000 variants identified to date. However, only 15% of these have been functionally characterized in vitro, demonstrating their impact (or lack of) on LDL receptor function. This study highlights the role of functional studies in genetic diagnosis and personalized medicine, using the Portuguese Familial hypercholesterolemia Study (EPHF) as an example of how these studies have clinical impact. Functional studies of LDLR are crucial for understanding how this receptor activity regulates cholesterol clearance. In a cohort of 1088 individuals (1073 heterozygotes and 15 homozygotes) with a clinical diagnosis of FH, 164 different LDLR variants were identified. To date, 70 of these variants have been functionally studied within the EPHF and 38 have been characterized by other labs. This functional characterization contributed to obtain a definitive genetic diagnosis for 847 individuals, marking a significant step towards personalized medicine and the effective management of FH. These studies not only improve the classification of LDLR variants but also directly influence treatment decisions and patient outcomes. By advancing the functional characterization of these variants, we contribute to more specialized and precise diagnostics, leading to more tailored therapeutic approaches for cholesterol-related disorders.
- Tabela da Composição de AlimentosPublication . Dias, Maria da GraçaApresentação sobre a Tabela da Composição de Alimentos, a Plataforma PortFIR e a importância das Bases de Dados da Composição de Alimentos.
- Clinical Research In Rare Diseases: The Example of HoFHPublication . Medeiros, AnaLecture on an Example of Homozygous Familial Hypercholesterolemia (HoFH), within the framework of Clinical Research in Rare Diseases.
- Qual o papel da epidemiologia no trabalho de um médico de saúde pública?Publication . Rodrigues, Ana PaulaApresentação de exemplos de utilização da epidemiologia no trabalho de observação, vigilância e investigação de um médico de saúde pública em exercício no Instituto Nacional de Saúde. Dirigida a médicos internos de Saúde Pública.