National Institute of Health Dr. Ricardo Jorge

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    Aplicação de biomarcadores de efeito na biomonitorização humana: teste do cometa e teste do micronúcleo

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    Sobre a utilização de biomarcadores de efeito em estudos de biomonitorização humana.FCT - 733032; UIDB/00009/2020; UIDP/00009/2020info:eu-repo/semantics/publishedVersio

    Resolving conflicting LDLR variants in ClinVar - Progress of the ClinGen familial hypercholesterolemia variant curation expert panel

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    Abstract publicado em: https://doi.org/10.1016/j.atherosclerosis.2023.06.716Familial hypercholesterolemia (FH) is the most common monogenic disorder of lipid metabolism. Genetic testing can confirm the clinical diagnosis, but there are currently over 3300 different variants in LDLR deposited in ClinVar and ~400 had conflicting classifications of pathogenicity. Here, we present the progress of LDLR variant classification by the FH Variant Curation Expert Panel (VCEP), composed of 13 reviewers, 17 curators, and 12 associated labs, with our LDLR consensus variant classification guidelines. Variants with conflicting classifications and other variants in the same codon (required to properly classify conflicting variants) are prioritized. Associated labs send internal variant case-level data, which is uploaded into the Variant Curation Interface (VCI) and supplemented by literature evidence. Each variant is assessed by one (very experienced) or two curators and approved by three reviewers before being officially published to ClinVar. As of December 2022, we have completed classification of 316 LDLR variants. Of those with prior conflicting classifications (n=165), 33% were classified as Pathogenic/Likely pathogenic (P/LP), 9% as Benign/Likely benign (B/LB), 55% as Variant of Uncertain Significance (VUS) by insufficient evidence and only 3% remained conflicting. Of the remaining 135 variants, 53% were classified as P/LP, 2% as B/LB and 45% as VUS. Until May 2023, we will evaluate 451 LDLR variants, 247 of them with prior conflicting classifications. Ultimately, efforts of the FH VCEP are aimed at improving FH genetic diagnosis, which relies on accurate LDLR variant classification. FH VCEP’s guidelines significantly decrease conflicting classifications, which will be especially helpful to the FH community.N/

    Bioguided Identification of Active Antimicrobial Compounds from Asphodelus bento-rainhae and Asphodelus macrocarpus Root Tubers

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    Root tubers of Asphodelus bento-rainhae subsp. bento-rainhae (AbR), a vulnerable endemic species, and Asphodelus macrocarpus subsp. macrocarpus (AmR) have traditionally been used in Portugal to treat inflammatory and infectious skin disorders. The present study aims to evaluate the in vitro antimicrobial activity of crude 70% and 96% hydroethanolic extracts of both medicinal plants, specifically against multidrug-resistant skin-related pathogens, to identify the involved marker secondary metabolites and also to assess the pre-clinical toxicity of these medicinal plant extracts. Bioguided fractionation of the 70% hydroethanolic extracts of both species using solvents of increasing polarity, namely diethyl ether (DEE: AbR-1, AmR-1), ethyl acetate (AbR-2, AmR-2) and aqueous (AbR-3, AmR-3) fractions, enabled the identification of the DEE fractions as the most active against all the tested Gram-positive microorganisms (MIC: 16 to 1000 µg/mL). Furthermore, phytochemical analyses using TLC and LC-UV/DAD-ESI/MS techniques revealed the presence of anthracene derivatives as the main constituents of DEE fractions, and five known compounds, namely 7'-(chrysophanol-4-yl)-chrysophanol-10'-C-beta-D-xylopyranosyl-anthrone (p), 10,7'-bichrysophanol (q), chrysophanol (r), 10-(chrysophanol-7'-yl)-10-hydroxychrysophanol-9-anthrone (s) and asphodelin (t), were identified as the main marker compounds. All these compounds showed high antimicrobial activity, particularly against Staphylococcus epidermidis (MIC: 3.2 to 100 µg/mL). Importantly, no cytotoxicity against HepG2 and HaCaT cells (up to 125 µg/mL) for crude extracts of both species and genotoxicity (up to 5000 µg/mL, with and without metabolic activation) for AbR 96% hydroethanolic extract was detected using the MTT and Ames tests, respectively. Overall, the obtained results contribute to the concrete validation of the use of these medicinal plants as potential sources of antimicrobial agents in the treatment of skin diseases.This research was funded by the Foundation for Science and Technology/MCTES (FCT, Portugal) through national funds to iMed.ULisboa (UIDP/04138/2020, UIDB/04138/2020), to CECA (UIDB/00211/2020) and to MEtRICs (UIDP/04077/2020, UIDB/04077/2020) research projects, as well as a doctoral scholarship (SFRH/BD/125310/2016) granted to the first authorinfo:eu-repo/semantics/publishedVersio

    Investigation of 29 Antimicrobial Compounds in Soil Using Newly Developed UHPLC-MS/MS Method

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    This article belongs to the Section Analytical Chemistry)While the prudent and reasonable use of veterinary antimicrobial agents in food-producing animals is necessary, researchers over the decades have shown that these antimicrobial agents can spread into the environment through livestock manure and wastewater. The analysis of the occurrence of antimicrobial compounds in soil samples is of a great importance to determine potential impacts on human and animal health and the environment. In this study, an affordable, rugged and simple analytical method has been developed for the determination of twenty-nine antimicrobial compounds from five different classes (tetracyclines, fluoro(quinolones), macrolides, sulfonamides and diaminopirimidines). Liquid-liquid extraction (LLE) with extract filtration combined with ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) was the best strategy for the simultaneous determination of all analytes. The developed method was validated according to the Commission Implementing Regulation (EU) 2021/808. The limit of detections (LODs) ranged from 0.5 to 2.0 µg/kg, while the limit of quantitation (LOQ) was established at 1.0 to 20.0 µg/kg. The developed method was successfully applied for the determination of antimicrobial residues in one hundred and eighteen soil samples obtained from four European countries (Austria, Czech Republic, Estonia and Portugal). Doxycycline in the concentration levels of 9.07 µg/kg-20.6 µg/kg was detected in eight of the analysed samples. Samples were collected from areas where natural fertilizers (swine or cow manure) were applied. Our method can be efficiently used to monitor anti-microbial compounds in soil samples.This research was supported by funding from the European Union’s Horizon 2020 Research and Innovation programme under grant agreement No. 773830: One Health European Joint Programme (project FED-AMR, No. JRP15-AMR2.1-FED-AMR). Research at the National Veterinary Research Institute (PIWet), Poland, was also partially supported by the Polish Ministry of Education and Science from the funds for science in the years 2018–2022 allocated for the implementation of a co-financed international project. Research at Centre for the Studies of Animal Science (CECA), University of Porto, Portugal, was also supported by FCT/MCTES [UIDB/00211/2020] through national funds.info:eu-repo/semantics/publishedVersio

    In Vitro Cytotoxicity and Genotoxicity Assessment of Novel Cellulose Nanomaterials using intestinal cells

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    Cellulose nanomaterials (CNMs) have been investigated for several applications, including in food and food packaging (e.g. as candidates for zero-calorie filler/thickener/stabilizers; as substitutes of petroleum-based food packaging materials). The widening of these applications will lead to human exposure via oral route, and potentially, to adverse health outcomes. To contribute to the CNMs safety evaluation, the aim of this study was to analyse the in vitro cytotoxicity and genotoxicity of two new micro/nanofibrillated celluloses (CMF/CNFs), using the HT29-MTX-E12 human intestinal cell model. CNMs were synthetized from industrial Eucalyptus globulus kraft and their physicochemical properties were characterized. Upon cells exposure to 3.1 - 200 μg/mL of CNMs during 24 h, the cytotoxicity was evaluated by the MTT and clonogenic assays, and the genotoxicity by the cytokinesis block micronucleus (CBMN) and comet assays. None of the CNMs was cytotoxic in the concentration-range tested. Concerning genotoxicity assessment, CMF induced a significant level of DNA damage (comet assay) in cells exposed for 3h to 25, 50 and 100 µg/mL and for 24h, to 50 µg/mL, compared with controls. No increases were observed with the FPG-modified comet assay compared with negative control. Cells treatment with the CNF for 3h significantly increased DNA damage at 14.3, 25, 50 µg/mL while a 24h treatment produced significant damage at 50 µg/mL, compared with control. For the latter concentration, induction of oxidative DNA damage was observed for both time points. In contrast, no increase in chromosomal damage was observed using the CBMN assay upon 52h of exposure. To our knowledge, this is the first study in which CNMs were evaluated for their genotoxic effects using the HT29MTX-E12 cell model, relevant for their potential ingestion. Our findings show that cytotoxicity, the endpoint generally used to assess their biocompatibility, is not sufficient to assess their safety to humans. Ongoing studies including the in vitro simulation of human digestion will allow a more comprehensive assessment of CNMs safety. This should be done at an early stage of their development, to ensure their sustainable and innovative application in food technology.FCT/MCTES projects PTDC/SAUPUB/29481/2017; PTDC/SAUPUB/32587/2017; UIDB/00009/2020 and UIDP/00009/2020. NV holds a FCT/MCTES Ph.D. Scholarship 2020.07168.BD. University of Coimbra for producing and characterising the CMNs.info:eu-repo/semantics/publishedVersio

    Sustained increase of paediatric invasive Streptococcus pyogenes infections dominated by M1UK and diverse emm12 isolates, Portugal, September 2022 to May 2023

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    Portuguese Group for the Study of Streptococcal Infections: Margarida Pinto, Miguel Seruca, João Marques, Isabel Peres, Teresa Pina, Isabel Lourenço, Teresa Ferreira, Cristina Marcelo, Isabel Daniel, Odete Chantre, Teresa Vaz, Marília Gião, Rui Ferreira, Rui Tomé Ribeiro, Celeste Pontes, Luísa Boaventura, Catarina Chaves, Teresa Reis, Henrique Oliveira, Catarina Chaves, Mariana Silva, Ana Aguiar, Hugo Loureiro, Adriana Pedrosa, Hermínia Costa, Maria Fátima Silva, Maria Amélia Afonso, Mariana Fardilha, Natália Novais, Isabel Brito, Luís Marques Lito, Ana Bruschy Fonseca, Filomena Martins, Maria Ana Pessanha, Elsa Gonçalves, Teresa Morais, Cristina Toscano, Paulo Lopes, Angelina Lameirão, Gabriela Abreu, Aurélia Selaru, Ana Paula Mota Vieira, Margarida Tomaz, Cláudia Ferreira, Marta Nicolau, Maria Helena Ramos, Ana Paula Castro, Virgínia Lopes, Fernando Fonseca, Ana Paula Castro, Nuno Canhoto, Teresa Afonso, Ilse Fontes, Paulo Martinho, Gina Marrão, Ana Domingos, José Grossinho, Manuela Ribeiro, Helena Gonçalves, Alberta Faustino, Maria Cármen Iglesias, Maria Paula Pinheiro, Rui Semedo, Adriana Coutinho, Luísa Gonçalves, Olga Neto, Luísa Sancho, José Diogo, Filipa Fortunato, Isabel Nascimento, Nadiya Kruptsala, Cláudia Fidalgo, Elmano Ramalheira, Raquel Diaz, Sónia Ferreia, Inês Cravo Roxo, Isabel Vale, Maria João Tomás, Maria Antónia Read, Valquíria Alves, Margarida Monteiro, Margarida Rodrigues, José Mota Freitas, Sandra Vieira, Elsa Calado, Paula Pinto, Ana Custódio, Maria Favila Menezes, José Germano de Sousa, Mariana Bettencourt Viana, Marvin Oliveira, Isaura Terra, Vitória Rodrigues, Sofia Marques, Joana Selada, Patrícia Pereira, Jesuína Duarte, Paula Pinto, Ezequiel Moreira, Adília Vicente, Fátima Vale, Joana Ramos, Rita Gralha, Ana Helena Correia, Paula Gama, Catarina Silva-Costa, Joana Gomes-Silva, Marcos Pinho, Célia Rodrigues Bettencourt, Miguel Pinto; Portuguese Study Group of Paediatric Invasive Streptococcal Disease: Sónia Aires, Eurico Gaspar, Manuela Ferreira, Fernanda Pereira, Graça Pombo, Maria José Dinis, Paulo Teixeira, José Amorim, Cláudia Monteiro, Diana Moreira, Sofia Arosa, Laura Marques, Margarida Tavares, Maria Manuel Zarcos, Sílvia Almeida, Fernanda Rodrigues, Jorge Rodrigues, Pedro Carvalho, Catarina Gouveia, Ana Isabel Carvalho, Alexandra Costa, Elsa Gonçalves, Filipa Prata, João Calado Nunes, Julieta Morais, Florbela Cunha, Paula Correia, Ana Margarida Chaves, Sofia Lima, João Neves, João Bivar, Pedro Flores, Sofia Fraga, Isabel Brito, Cristina Didelet, Estela Veiga, Carla Cruz, Graça Seves, Céu Novais, Maria João Virtuoso, Nancy Guerreiro, Francisco Gomes, Dora Gomes, Carolina Gonçalves, Nuno Canhoto.Since autumn 2022, observed numbers of paediatric invasive group A Streptococcus infections in Portugal (n = 89) were higher than in pre-COVID-19 seasons. Between September 2022 and May 2023, the dominant diagnoses were pneumonia (25/79), mostly with empyema (20/25), and sepsis (22/79). A number of cases required admission to intensive care (27/79) and surgery (35/79), and the case fatality rate was 5.1% (4/79). Genomic sequencing (n = 55) revealed multiple genetic lineages, dominated by the M1UK sublineage (26/55) and more diverse emm12 isolates (12/55).RM was supported by the Fundação para a Ciência e Tecnologia (FCT) (grant 2020.08493.BD).info:eu-repo/semantics/publishedVersio

    Unraveling the genetic background of individuals with a clinical familial hypercholesterolemia phenotype

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    investigators of the Portuguese FH Study: Mafalda Bourbon, Quitéria Rato, Ana Catarina Alves, Ana Margarida Medeiros, Ana Catarina Gomes, Ana Cristina Ferreira, Ana Gaspar, Ana Margarida Marques, Ana Maria Garabal, Ana Paula Bogalho, Ana Rita Pereira, Anabela Raimundo, André Travessa, Andreia Lopes, António Afonso, António Furtado, António Guerra, António Monteiro, António Trindade, Armindo Ribeiro, Bernardo Dias Pereira, Bernardo Marques, Carla Laranjeira, Catarina Senra Moniz, Cecília Frutuoso, Cláudia Falcão Reis, Cláudia Rodrigues, Clementina Fernandes, Conceição Ferreira, Daniel Ferreira, Diogo Torres, Elisabete Martins, Elsa Gaspar, Fabiana Pimentel, Fernando Simões, Francisco Araújo, Francisco Silva, Goreti Lobarinhas, Graça Morais, Guida Gama, Guilherme Lourenço, Helena Mansilha, Helena Pereira, Heloísa Santos, Henedina Antunes, Inês Batista Gomes, Inês Colaço, Isabel Azevedo, Isabel Palma, João Anselmo, João Porto, João Ramos, João Sequeira Duarte, Jorge Pintado Alves, José Miguel Salgado, José Pereira de Moura, Leonor Sassetti, Lina Cardoso Ramos, Luísa Diogo Matos, Luísa Mota Vieira, Luísa Pires, Márcio de Moura, Margarida Bruges, Margarida Venâncio, Maria do Rosário Barroso, Maria João Virtuoso, Maria Luísa Gonçalves, Mário Martins Oliveira, Mendes Nunes, Miguel Costa, Miguel Mendes, Miguel Toscano Rico, Mónica Tavares, Natalina Miguel, Oana Moldovan, Olga Azevedo, Patrícia Lipari Pinto, Patrícia Pais, Patrícia Vasconcelos, Paula Garcia, Paula Martins, Pedro Marques da Silva, Piedade Lemos, Quitéria Rato, Raquel Coelho, Raquel Gouveia da Silva, Raquel Ribeiro, Rita Jotta de Oliveira, Roberto Pinto, Sandra Pereira, Sérgio Ferreira Cristina, Sílvia Sequeira, Susana Correia, Tânia Vassalo, Tiago Pack, Vânia Martins, Vera Frazão Vieira.Familial hypercholesterolemia (FH) is a common genetic disorder of lipid metabolism caused by pathogenic/likely pathogenic variants in LDLR, APOB, and PCSK9 genes. Variants in FH-phenocopy genes (LDLRAP1, APOE, LIPA, ABCG5, and ABCG8), polygenic hypercholesterolemia, and hyperlipoprotein (a) [Lp(a)] can also mimic a clinical FH phenotype. We aim to present a new diagnostic tool to unravel the genetic background of clinical FH phenotype. Biochemical and genetic study was performed in 1,005 individuals with clinical diagnosis of FH, referred to the Portuguese FH Study. A next-generation sequencing panel, covering eight genes and eight SNPs to determine LDL-C polygenic risk score and LPA genetic score, was validated, and used in this study. FH was genetically confirmed in 417 index cases: 408 heterozygotes and 9 homozygotes. Cascade screening increased the identification to 1,000 FH individuals, including 11 homozygotes. FH-negative individuals (phenotype positive and genotype negative) have Lp(a) >50 mg/dl (30%), high polygenic risk score (16%), other monogenic lipid metabolism disorders (1%), and heterozygous pathogenic variants in FH-phenocopy genes (2%). Heterozygous variants of uncertain significance were identified in primary genes (12%) and phenocopy genes (7%). Overall, 42% of our cohort was genetically confirmed with FH. In the remaining individuals, other causes for high LDL-C were identified in 68%. Hyper-Lp(a) or polygenic hypercholesterolemia may be the cause of the clinical FH phenotype in almost half of FH-negative individuals. A small part has pathogenic variants in ABCG5/ABCG8 in heterozygosity that can cause hypercholesterolemia and should be further investigated. This extended next-generation sequencing panel identifies individuals with FH and FH-phenocopies, allowing to personalize each person's treatment according to the affected pathway.Was supported by the Portuguese Cardiology Society (grant number: D13123) and FCT (grant numbers: PTDC/SAU-GMG/101874/2008 and PTDC/SAUSER/29180/2017). This work was also supported by UIDB/04046/2020 (DOI: 10.54499/UIDB/04046/2020) and UIDP/04046/2020 (DOI: 10.54499/UIDP/04046/2020) center grants from FCT, Portugal (to BioISI).info:eu-repo/semantics/publishedVersio

    Avaliação da Qualidade Nutricional de Alimentos Processados de Base Vegetal

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    Dissertação de Mestrado em Qualidade Alimentar e Saúde, apresentada à Faculdade de Farmácia da Universidade de Lisboa, 2023.Orientadora Doutora Carla Alexandra Fino Alberto da Motta do Instituto Nacional de Saúde Doutor Ricardo Jorge e coorientada pela Professora Doutora Maria Eduardo Costa Morgado Figueira da Faculdade de Farmácia, Universidade de Lisboa.Nos últimos anos, o consumo de dietas de base vegetal tem aumentado significativamente devido sobretudo ao aumento de evidência científica acerca dos benefícios deste tipo de alimentação, nomeadamente no que diz respeito ao combate às doenças não transmissíveis. Para além disso, verifica-se que a comercialização de produtos alimentares à base de plantas tem vindo a aumentar, apresentando-se como alternativa aos produtos de origem animal. O principal objetivo deste trabalho, foi a análise da qualidade nutricional, incluindo a qualidade proteica, de hambúrgueres veganos, prontos a comer, disponíveis na área da grande Lisboa. Para isso, procedeu-se à recolha da informação nutricional de hambúrgueres ultraprocessados (HUP) e à determinação dos macronutrientes, bem como de minerais, oligoelementos e aminoácidos, de forma a calcular a qualidade nutricional e proteica, em hambúrgueres prontos a comer (HPC) em restaurantes. Em relação, ao perfil nutricional dos HPC apresentam teores proteicos entre 13 gramas e 31 g/porção de alimento, enquanto nos HUP varia entre os 2,9 gramas e 30 gramas. Do ponto de vista da qualidade proteica os HPC apresentaram em todas as amostras os aminoácidos sulfurados como limitantes. Os teores de gordura encontram-se entre os 3,2 g/100g e 35 g/100g . No que diz respeito ao perfil em ácidos gordos, os saturados contribuem entre 2% e 28 % do aporte diário por 2000 Kcal. O teor de fibra contribui com 5% a 69% da dose diária recomendada de 25 g/dia. No que diz respeito ao sal, verificou-se um contributo para a dose recomendada de 5g diárias entre 23% a 75% para os HPC e 16% a 30% nos HUP. Existem no mercado muitos HUP e HPC cuja qualidade nutricional pode ser questionável. Com este trabalho esperamos contribuir para alertar para uma escolha informada e saudável, destes produtos, bem como na ajuda para a reformulação deste tipo de produto.In recent years, the consumption of plant-based diets has increased significantly, mainly due to the increase in scientific evidence about the benefits of this type of food, concerning the fight against non-communicable diseases. In addition, the commercialization of plant-based food products has been increasing, presenting itself as an alternative to products of animal origin. The main objective of this work was to analyze the nutritional quality, including protein quality, of ready-to-eat vegan burgers available in the greater Lisbon area. For this, nutritional information was collected from ultra-processed hamburgers (HUP), and the determination of macronutrients, as well as minerals, trace elements and amino acids, in order to calculate the nutritional and protein quality in ready-to-eat hamburgers (HPC) in restaurants. Concerning the nutritional profile of HPCs, they present protein levels between 13 grams and 31 g/portion of food, while in HUPs, it varies between 2,9 grams and 30 grams. From the point of view of protein quality, the HPC showed in all samples the sulfur amino acids as limiting. The fat contents are between 3.2 g/100g and 35 g/100 g. Regarding the fatty acid profile, saturated fatty acids contribute between 2 and 28% of the daily intake per 2000 Kcal. The fiber content contributes 5% to 69% of the recommended daily allowance of 25 g/day. With regard to salt, there was a contribution to the recommended dose of 5g daily between 23% to 75% for HPC and 16% to 30% for HUP. Overall, many HUPs and HPCs on the market may have questionable nutritional quality. With this work, we hope to raise awareness of an informed and healthy choice of these products, as well as helping to reformulate this type of product.info:eu-repo/semantics/publishedVersio

    Heat-related cardiorespiratory mortality: Effect modification by air pollution across 482 cities from 24 countries

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    Highlights: - Heat effect modification by air pollution on cardiovascular and respiratory mortality was investigated across 482 cities.- Heat effect was seen to be significantly modified by air pollutants PM10, PM2.5, O3, and NO2. -This study is the most extensive research to date investigating the heat effect modification on cardiovascular and respiratory mortality. - This is the first-ever study to deeply investigate effect modifications by air pollutants such as PM2.5 and NO2.Background: Evidence on the potential interactive effects of heat and ambient air pollution on cause-specific mortality is inconclusive and limited to selected locations. Objectives: We investigated the effects of heat on cardiovascular and respiratory mortality and its modification by air pollution during summer months (six consecutive hottest months) in 482 locations across 24 countries. Methods: Location-specific daily death counts and exposure data (e.g., particulate matter with diameters ≤ 2.5 µm [PM2.5]) were obtained from 2000 to 2018. We used location-specific confounder-adjusted Quasi-Poisson regression with a tensor product between air temperature and the air pollutant. We extracted heat effects at low, medium, and high levels of pollutants, defined as the 5th, 50th, and 95th percentile of the location-specific pollutant concentrations. Country-specific and overall estimates were derived using a random-effects multilevel meta-analytical model. Results: Heat was associated with increased cardiorespiratory mortality. Moreover, the heat effects were modified by elevated levels of all air pollutants in most locations, with stronger effects for respiratory than cardiovascular mortality. For example, the percent increase in respiratory mortality per increase in the 2-day average summer temperature from the 75th to the 99th percentile was 7.7% (95% Confidence Interval [CI] 7.6-7.7), 11.3% (95%CI 11.2-11.3), and 14.3% (95% CI 14.1-14.5) at low, medium, and high levels of PM2.5, respectively. Similarly, cardiovascular mortality increased by 1.6 (95%CI 1.5-1.6), 5.1 (95%CI 5.1-5.2), and 8.7 (95%CI 8.7-8.8) at low, medium, and high levels of O3, respectively. Discussion: We observed considerable modification of the heat effects on cardiovascular and respiratory mortality by elevated levels of air pollutants. Therefore, mitigation measures following the new WHO Air Quality Guidelines are crucial to enhance better health and promote sustainable development.Masna Rai, Massimo Stafoggia, Francesca K. de’ Donato, Sofia Zafeiratou, Liliana Vazquez Fernandez, Siqi Zhang, Klea Katsouyanni, Evangelia Samoli, Shilpa Rao, Antonio Gasparrini, Pierre Masselot, and Alexandra Schneider were supported by the European Union’s Horizon 2020 Project Exhaustion (Grant ID: 820655). Joana Madureira was supported by the Fundação para a Ciência e a Tecnologia (FCT) (Grant SFRH/BPD/115112/2016).info:eu-repo/semantics/publishedVersio

    Global short-term mortality risk and burden associated with tropical cyclones from 1980 to 2019: a multi-country time-series study

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    Background: The global spatiotemporal pattern of mortality risk and burden attributable to tropical cyclones is unclear. We aimed to evaluate the global short-term mortality risk and burden associated with tropical cyclones from 1980 to 2019. Methods: The wind speed associated with cyclones from 1980 to 2019 was estimated globally through a parametric wind field model at a grid resolution of 0·5° × 0·5°. A total of 341 locations with daily mortality and temperature data from 14 countries that experienced at least one tropical cyclone day (a day with maximum sustained wind speed associated with cyclones ≥17·5 m/s) during the study period were included. A conditional quasi-Poisson regression with distributed lag non-linear model was applied to assess the tropical cyclone-mortality association. A meta-regression model was fitted to evaluate potential contributing factors and estimate grid cell-specific tropical cyclone effects. Findings: Tropical cyclone exposure was associated with an overall 6% (95% CI 4-8) increase in mortality in the first 2 weeks following exposure. Globally, an estimate of 97 430 excess deaths (95% empirical CI [eCI] 71 651-126 438) per decade were observed over the 2 weeks following exposure to tropical cyclones, accounting for 20·7 (95% eCI 15·2-26·9) excess deaths per 100 000 residents (excess death rate) and 3·3 (95% eCI 2·4-4·3) excess deaths per 1000 deaths (excess death ratio) over 1980-2019. The mortality burden exhibited substantial temporal and spatial variation. East Asia and south Asia had the highest number of excess deaths during 1980-2019: 28 744 (95% eCI 16 863-42 188) and 27 267 (21 157-34 058) excess deaths per decade, respectively. In contrast, the regions with the highest excess death ratios and rates were southeast Asia and Latin America and the Caribbean. From 1980-99 to 2000-19, marked increases in tropical cyclone-related excess death numbers were observed globally, especially for Latin America and the Caribbean and south Asia. Grid cell-level and country-level results revealed further heterogeneous spatiotemporal patterns such as the high and increasing tropical cyclone-related mortality burden in Caribbean countries or regions. Interpretation: Globally, short-term exposure to tropical cyclones was associated with a significant mortality burden, with highly heterogeneous spatiotemporal patterns. In-depth exploration of tropical cyclone epidemiology for those countries and regions estimated to have the highest and increasing tropical cyclone-related mortality burdens is urgently needed to help inform the development of targeted actions against the increasing adverse health impacts of tropical cyclones under a changing climate.Funding: This work was supported by the Australian Research Council (DP210102076) and the Australian National Health and Medical Research Council (GNT2000581). WH and RX were supported by China Scholarship Council funds (numbers 202006380055 and 201806010405). YG was supported by a Career Development Fellowship (GNT1163693) and Leader Fellowship (GNT2008813) of the Australian National Health and Medical Research Council. SL was supported by an Emerging Leader Fellowship of the Australian National Health and Medical Research Council (GNT2009866). TV received funding from the German Federal Ministry of Education and Research (BMBF) under the research project QUIDIC (01LP1907A), and through the CHIPS project, part of AXIS, an ERA-NET initiated by JPI Climate, and funded by FORMAS (Sweden), Deutsches Zentrum für Luft- und Raumfahrt (German Aerospace Center)/Bundesministerium für Bildung und Forschung (German Ministry of Education and Research) (grant number 01LS1904A), Agencia Estatal de Investigación (Spanish State Research Agency), and Agence Nationale de la Recherche (French National Agency for Research) with co-funding by the EU (grant number 776608). JM was supported by a fellowship of Fundação para a Ciência e a Tecnlogia (SFRH/BPD/115112/2016). AG was supported by the UK Medical Research Council (grant ID MR/R013349/1), the UK Natural Environment Research Council (grant ID NE/R009384/1), and the EU's Horizon 2020 project, Exhaustion (grant ID 820655). AT was supported by MCIN/AEI/10.13039/501100011033 (grant CEX2018-000794-S).info:eu-repo/semantics/publishedVersio

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