National Institute of Health Dr. Ricardo Jorge
Repositório Científico do Instituto Nacional de SaúdeNot a member yet
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Distribution of the West Nile Virus vector, Culex pipiens, in mainland Portugal: A geospatial modelling study
No full textBackground: Culex pipiens, Portugal’s most abundant mosquito, is a vector for several pathogens including the West Nile virus. Understanding its spatial distribution can contribute to vector-borne diseases control and public health planning, given Portugal’s favourable climate. National-level data on its spatial distribution, especially in relation to climatic variables is limited. We aimed to predict the suitability of Culex pipiens distribution in mainland Portugal, considering climatic factors.
Methods: A maximum entropy (Maxent) model was applied, using presence records for adult and larvae of Culex pipiens mosquitoes sampled across mainland Portugal between January 2017 and October 2023, as part of the REVIVE – Vector Surveillance Network program. Adults were sampled using CDC light traps and BG-Sentinel traps between May and October at random sites and year-round at point-of-entry sites. Larvae were sampled using dippers at breeding sites. Sampling bias was corrected by filtering presence records to one per 1 km2 cell grid. Climatic data, including temperature, precipitation and elevation, were used as predictors.
Results: Out of 6,859 records, 354 unique sites were obtained after filtering and cell-duplicate removal. Suitable habitats seem to be primarily in the northern and central coastal regions. Temperature was the most important predictor. Convenience sampling bias may be present.
Conclusions: Most West Nile virus case reports have come from southern Portugal, but Culex pipiens’s potential distribution covers the entire mainland territory, with seemingly higher distribution in the north. West Nile vector surveillance should be a priority in all regions to accurately assess transmission risk and implement effective control measures.Highlights: - Maxent was used to model suitable habitats for Culex pipiens in Portugal. - Culex pipiens’s suitability distribution covers the entire mainland territory. - Culex pipiens’s potential distribution is higher in the northern coast. - Region-specific strategies for WNV prevention and control are needed
Familial hypercholesterolemia in Portugal: characterization of genetic diagnosed cases in the Portuguese Study of Familial Hypercholesterolemia, 1999-2023
No full textHipercolesterolemia Familiar (FH) é uma condição autossómica semidominante causada por variantes patogénicas ou provavelmente patogénicas nos genes LDLR, APOB e PCSK9. A FH pode apresentar-se na forma monoalélica (FH heterozigótica) ou bialélica (FH homozigótica). A forma homozigótica é mais rara e com fenótipo mais grave. Indivíduos com FH homozigótica geralmente apresentam hipercolesterolemia severa (LDL>400mg/dL), xantomas e doença cardiovascular aterosclerótica (DCVA) prematura em idade jovem. Até 2023, foram referenciados ao Estudo Português de Hipercolesterolemia Familiar 1291 casos-índex. Neste estudo foram analisados os casos com FH homozigótica. Foram identificados 15 casos com FH homozigótica: 5 com a mesma variante bialélica no LDLR, 7 com variantes bialélicas diferentes no LDLR, 1 com variantes bialélicas diferentes no PCSK9, e 2 com variantes nos genes LDLR e APOB. A maioria dos indivíduos eram adultos (73%) e do sexo feminino (87%), 13% apresentando xantomas tendinosos e 36% com DCVA. Variantes de alelo nulo estão associadas a um fenótipo mais grave e a uma menor resposta ao tratamento, sendo necessária terapêutica independente da atividade do recetor de LDL. O diagnóstico genético permite identificar com precisão as variantes e os tipos de alelos, e implementar uma abordagem terapêutica mais personalizada nestes indivíduos.Familial Hypercholesterolemia (FH) is an autosomal semidominant condition caused by pathogenic or likely pathogenic variants in the LDLR, APOB, and PCSK9 genes. FH can manifest in a monoallelic form (heterozygous FH) or a biallelic form (homozygous FH). The homozygous form, which is rarer and has a more severe phenotype, with severe hypercholesterolemia (LDL>400mg/dL), xanthomas, and premature atherosclerotic cardiovascular disease (ASCVD) at a young age. This study aims to analyse cases of homozygous FH. Until 2023, 1291 index cases were referred to the Portuguese Familial Hypercholesterolemia Study. Among these, 15 cases were identified with homozygous FH: 5 with the same biallelic variant in LDLR, 7 with different biallelic variants in LDLR, 1 with different biallelic variants in PCSK9, and 2 with variants in both LDLR and APOB. Most individuals are adults (73%) and females (87%), with 13% presenting tendon xanthomas and 36% with ASCVD. Nul l allele variants were associated with a more severe phenotype and less responsive to treatments, requiring therapies with a mechanism of action independent of LDL receptor activity. Genetic diagnosis enables precise identification of variants and allele types, allowing personalized therapeutic approaches for these individuals
High burden of hospital morbidity and mortality due to Chagas disease in Bahia state, Northeast Brazil, 2000-2022
No full textChagas disease (CD) is a chronic condition associated with high morbidity and mortality in endemic regions of Brazil, particularly in the state of Bahia. The clinical-epidemiologic analysis of hospital admissions is strategic due to limited data on chronic CD infections and the general lack of access to diagnosis and treatment. This study examines sociodemographic and clinical-epidemiological patterns of hospital morbidity and mortality from CD and its temporal trends from 2000 to 2022 in Bahia, Northeast Brazil. A mixed ecological study was conducted using data from hospital and mortality information systems. We calculated the hospital case fatality and all-cause mortality rates for CD, analysing temporal trends through joinpoint regression. Out of 20,189,658 hospital admissions, 4,557 (0.02%) were associated with CD, yielding a hospital lethality of 0.10 per 100,000 inhabitants. Of 1,832,325 Death Certificates, 16,960 (0.93%) were attributed to CD, equating to 5.16 deaths per 100,000 inhabitants. The risk ratios for hospital case fatality and mortality were higher among males, residents of municipalities with a 'medium' Brazilian Deprivation Index, those in the Central-North region, and patients with megacolon. Hospital case fatality significantly increased among males, the elderly (≥70 years) and residents in municipalities with 'high' or 'very high' Brazilian Deprivation Index in the Central-North and Central-East regions. The all-cause mortality trend for CD also rose among women and in municipalities with 'high' and 'very high' Brazilian Deprivation Index across the Southwest, West, North and Central-East regions. Programmatic vulnerabilities related to healthcare access within the Unified Health System likely contributed to delayed diagnoses and the increasing severity of specific forms of CD.This study was supported by the IntegraChagas Brazil Project of the Ministry of Health of Brazil (TED No. 161/2019). Additional funding was provided by the Bahia State Research Support Foundation (FAPESB) through the 003/2017 Research Program for the Unified Health System (PPSUS), and by the Netherlands Hanseniasis Relief of Brazil (NHR Brazil). The National Council for Scientific and Technological Development (CNPq) also contributed, under the call MCTI/CNPq No. 01/2016, Process No. 433078/2016–2 and the Research Productivity Grant (PQ - CNPq - 316316/2023-7). Further support came from the Coordination for the Improvement of Higher Education Personnel (CAPES) through the Graduate Support Program (PROAP) of the Federal University of Ceará
HBM4EU E-waste study – An untargeted metabolomics approach to characterize metabolic changes during E-waste recycling
No full textE-waste contains hazardous chemicals that may be a direct health risk for workers involved in recycling. We conducted an untargeted metabolomics analysis of urine samples collected from male e-waste processing workers to explore metabolic changes associated with chemical exposures in e-waste recycling in Belgium, Finland, Latvia, Luxembourg, the Netherlands, Poland, and Portugal. Questionnaire data and urine samples were obtained from workers involved in the processing of e-waste (sorting, dismantling, shredding, pre-processing, metal, and non-metal processing), as well as from controls with no known occupational exposure. Pre- and post-shift urine samples were collected and analysed using ultrahigh-performance liquid chromatography-mass spectrometry (UPLC-MS). A total of 32 endogenous urinary metabolites were annotated with a Variable Importance in Projection (VIP) above 2, indicating that e-waste recycling is mainly associated with changes in steroid hormone and neurotransmitter metabolism, energy metabolism, bile acid biosynthesis, and inflammation. The highest VIP was observed for dopamine-o-quinone, which is linked to Parkinson’s disease. These and other changes in metabolism in workers employed in the processing of e-waste need further verification in targeted studies.Highlights: - Untargeted metabolomics is a novel tool to explore the effects of exposure; - E-waste recycling is connected to mixture exposure; - Exposure to a mixture of chemicals is associated with a multidirectional effect on metabolism; - Effects of exposure: inflammation, changes in hormones, neurotransmitters, bile acids, energy metabolism.This work has received external funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 733032 and received co-funding from the author’s organizations and/or Ministries. In addition, the Finnish Work Environment fund provided funding (grant no. 200345). The publication was financed by the Science Development Fund of the Warsaw University of Life Sciences – SGGW
Occupational exposure to wildland firefighting and its effects on systemic DNA damage
No full textBackground: Portugal is among the European Union countries more devastated by forest fires. Wildland firefighters are at the forefront of this battle, facing exposure to a wide range of harmful pollutants. Epidemiological studies have highlighted a potential link between occupational firefighting exposure and several diseases, including cancer. To date, very few studies have explored the biological mechanisms associated with such exposure. The present longitudinal study aims to assess changes in early effect biomarkers following wildland firefighters’ occupational exposure to a real wildfire event.
Methods: Paired blood samples from 59 healthy Portuguese wildland firefighters were collected at two different time points: before wildfire season and after a fire event during wildfire season. Sociodemographic variables (e.g., age, sex) and work-related factors (e.g., years of service) were assessed via a self-reported questionnaire. Levels of early effect biomarkers, such as primary DNA damage and oxidative DNA damage (oxidised purines) were assessed via comet assay. DNA double-strand breaks (DSBs) were evaluated by phosphorylated H2AX (γH2AX). Moreover, hydroxylated polycyclic aromatic hydrocarbon metabolites (OHPAHs) and metal(loid)s were quantified in urine samples. The influence of urinary OHPAHs, urinary metal(loid)s, and other exposure-related factors (e.g., firefighting duration) on changes (Δ) in early effect biomarkers (post-vs. baseline levels) was investigated.
Results: Firefighting activities led to a significant increase in both primary DNA damage and oxidative DNA damage by 22 % (95 % CI: 1.11–1.35; p < 0.05) and 23 % (95 % CI: 1.04–1.45; p < 0.05), respectively. Results from linear regression revealed that per each unit increase of urinary 2-hydroxyfluorene (2-OHFlu) (μmol/mol creatinine), the risk of ⧍ oxidative DNA damage increased by 20 % [FR: 1.20 (1.09–1.32); p < 0.01]. Additionally, each unit increase in urinary cesium (Cs) (μg/L) resulted in a significant 4 % increase in Δ primary DNA damage [FR: 1.04 (1.01–1.06); p < 0.05] and a 3 % increase in Δ oxidative DNA damage [FR: 1.03 (1.01–1.05); p < 0.05]. Post-exposure levels of γH2AX were significantly correlated with urinary 2-OHFlu levels assessed after firefighting (r = 0.30; p < 0.05). Furthermore, exposure duration and reported breathing difficulties during firefighting were significantly associated with increased levels of primary DNA damage.
Conclusion: Results obtained provide insights into the potential human health effects of wildland firefighting occupational exposure at the genetic and molecular levels, offering new and important mechanistic data. These findings are crucial for implementing health and safety measures, recommendations, and best practices to mitigate occupational risks and protect the health of wildland firefighters.This work received financial support from the project PCIF/SSO/0017/2018 (https://doi.org/10.54499/PCIF/SSO/0017/2018) by the Fundação para a Ciência e a Tecnologia (FCT), Ministério da Ciência, Tecnologia e Ensino Superior (MCTES), through national funds. This work is financed by national funds through the FCT within the scope of projects UIDB/04750/2020 (https://doi.org/10.54499/UIDB/04750/2020) and LA/P/0064/2020 (https://doi.org/10.54499/LA/P/0064/2020). Filipa Esteves was supported by National Funds through FCT, under the Ph.D. fellowship UI/BD/150783/2020. The work of Stefano Bonassi was supported by the Italian Ministry of Health (Ricerca Corrente), Rome, Italy, and by the Competitive Funding for University Research Projects [Finanziamento competitivo di progetti di ricerca di ateneo (FIN/RIC)] San Raffaele University, Rome, Italy
SCCS Opinion on Biphenyl-2-ol and Sodium 2-biphenylolate used in cosmetic products (CAS/EC No. 90-43-7/201-993-5 and 132-27-4/205-055-6)– SCCS/1669/24
No full textCorrection: NAM Journal. 2025 Oct 14: 100059. doi:10.1016/j.namjnl.2025.100059Highlights: -o-Phenylphenol (OPP) is safe when used as preservative up to a maximum concentration of 0.2 % in rinse-off cosmetic products; - o-Phenylphenol (OPP) is safe when used as preservative up to a maximum concentration of 0.15 % in leave-on cosmetic products; - Sodium o-Phenylphenate is safe when used as preservative up to a maximum concentration of 0.2 % in rinse-off cosmetic products; - Sodium o-Phenylphenate is safe when used as preservative up to a maximum concentration of 0.15 % in leave-on cosmetic products; - OPP and Sodium o-Phenylphenate, when used together, should not exceed the maximum concentration 0.15 % in leave-on cosmetic products; - OPP and Sodium o-Phenylphenate, when used together, should not exceed the maximum concentration 0.2 % in rinse-off cosmetic products; - Since this safety dossier related to dermally applied products only, the SCCS did not consider oral and inhalation routes; - This assessment did not cover the safety of O-Phenylphenol and Sodium o-Phenylphenate for the environment
The role of eIF3 subunits in the mechanism of nonsense-mediated mRNA decay
No full textPremature translation-termination codons (PTCs) or nonsense codons) can arise from mutations in germ or somatic cells. The introduction of a PTC into an mRNA can trigger nonsense-mediated decay (NMD), an important mRNA surveillance mechanism that typically recognizes and degrades mRNAs containing PTCs to prevent the synthesis of C-terminally truncated proteins potentially toxic for the cell. The physiological importance of NMD is manifested by the fact that about one third of genetic disease-associated mutations generate PTCs.
The mammalian translation initiation factor 3 represents the most complex eukaryotic initiation factor (eIF) in mammalian cells. This factor comprises 13 subunits (eIF3a to eIF3m), each one playing an important role in translational control. Disruption of eIF3 initiation factor activity can lead not only to cancer but also neural physiological alterations, and to act as a mediator of infection cascade. Although some eIF3 subunits (for example, e and g) have been implicated in NMD, others were not studied yet. With the aim to identify other eIF3 subunits involved in NMD, we have depleted each one of the eIF3 subunits in HeLa cells and tested its effect in the expression of PTC-free or PTC- containing reporter human β-globin genes. Our data show that eIF3l and eIF3j subunits have an important role in targeting mRNAs for NMD. We will describe the molecular mechanisms underlying these observations.This work was partially supported by Fundacão para a Ciência e a Tecnologia (PTDC/BIM-MEC/3749/2014 and UID/MULTI/04046/2013 to BioISI from FCT/MCTES/PIDDAC).N/
The function of DIS3L2 in the mechanism of nonsense-mediated mRNA decay
No full textIn the flow of information from DNA to mRNA to proteins, mRNAs undergo a number of processing steps, since they are synthesized in the nucleus, until they are translated in the cytoplasm. Eukaryotic cells tightly control the fidelity of this process, via quality control pathways, among them, the nonsense-mediated mRNA decay (NMD). NMD recognizes and degrades mRNAs harboring premature translation-termination codons (PTCs), protecting the cell from potentially harmful truncated proteins. However, NMD can also regulate normal and fully functional mRNA levels, arising as a surveillance and a gene expression regulation pathway. A new branch of the NMD pathway is starting to be revealed, which is characterized by the involvement of the DIS3L2 3’ to 5’ exoribonuclease. This protein has special relevance, given its exosome-independent action and its uridylation-mediated decay. In addition, mutations on this ribonuclease induce deregulation of cell-cycle genes leading to a faster cell growth and decreased chromosome stability, while DIS3L2 downregulation enhances cancer stem cell properties.
Several lines of evidence point to an oncogenic role of DIS3L2 and its mediated decay over a number of NMD targets, however further research is needed to unveil the mechanism by which this nuclease is involved in NMD and how it mediates cancer related processes. In this work, we show the DIS3L2 involvement in the NMD target regulation, by its dependent action on the NMD central player, UPF1. We also aim to analyze how DIS3L2 and uridylation regulate the human transcriptome, in order to shed light on how this ribonuclease is related to NMD and how its deregulation contributes to tumorigenesis. For this purpose, high-throughput mRNA sequencing has been performed in the SW480 colorectal cancer cell line depleted of DIS3L2 or DIS3L2 plus terminal uridylyl transferases (TUTases), TUT4 and TUT7.This work was partially supported by Fundação para a Ciência e a Tecnologia (FCT), Portugal (PTFC/BIM-MEC/3749/2014 to LR and UID/MULTI/04046/2013 centre grant to BioISI). PJdC and JFG-M are recipients of a fellowship from BioSys PhD programme (SFRH/BD/52495/2014 to PJdC, SFRH/BD/52492/2014 to HAS, and PD/BD/142898/2018 to JFG-M) and JM is a posdoc
fellow (SFRH/BPD/98360/2013) from FCT. Work at ITQB NOVA was financially supported by: Project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular) funded by the European Regional Development Fund (FEDER) through COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI) and by national funds through FCT: project PTDC/BIAMIC/1399/2014 to CMA and project PTFC/BIM-MEC/3749/2014 to SCV. SCV was financed by program IF of FCT [ref. IF/00217/2015]. MS was financed by an FCT grant [SFRH/BPD/109464/2015]. We thank Dr. V. Narry Kim from Seoul National University (Seoul, Korea), who kindly provided us with the pCK-FLAG-TUT4 and pCK-FLAG-TUT7 vectors.info:eu-repo/semantics/publishedVersio
