Instituto Nacional de Saúde Doutor Ricardo Jorge
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- Estrogen-mediated inhibition of purine metabolism and cell cycle arrest as a novel therapeutic approach in colorectal cancerPublication . Zamer, Batoul Abi; Shafarin, Jasmin; Sharaf, BasmaM.; Hroub, HamzaM. Al; Soares, Nelson C.; Semreen, Mohammad H.; Hamad, Mawieh; Muhammad, Jibran SualehPurine metabolism is upregulated in various cancers including colorectal cancer (CRC). While previous work has elucidated the role of estrogen (E2) in metabolic reprogramming and ATP production, the effect of E2 on purine metabolism remains largely unknown. Herein, the impact of E2 signalling on purine metabolism in CRC cells was investigated using metabolome and transcriptome profiling of cell extracts derived from E2-treated HCT-116 cells with intact or silenced estrogen receptor alpha (ERα). Purine metabolic pathway enrichment analysis showed that 27 genes in the de novo purine synthesis pathway were downregulated in E2-treated CRC cells. Downstream consequences of E2 treatment including the induction of DNA damage, cell cycle arrest, and apoptosis were all shown to be ERα-dependent. These findings demonstrate, for the first time, that E2 exerts a significant anti-growth and survival effect in CRC cells by targeting the purine synthesis pathway in a ERα-dependent manner, meriting further investigation of the therapeutic utility of E2 signalling in CRC.
- Global short-term mortality risk and burden associated with tropical cyclones from 1980 to 2019: a multi-country time-series studyPublication . Huang, Wenzhong; Li, Shanshan; Vogt, Thomas; Xu, Rongbin; Tong, Shilu; Molina, Tomás; Masselot, Pierre; Gasparrini, Antonio; Armstrong, Ben; Pascal, Mathilde; Royé, Dominic; Sheng Ng, Chris Fook; Vicedo-Cabrera, Ana Maria; Schwartz, Joel; Lavigne, Eric; Kan, Haidong; Goodman, Patrick; Zeka, Ariana; Hashizume, Masahiro; Diaz, Magali Hurtado; De la Cruz Valencia, César; Seposo, Xerxes; Nunes, Baltazar; Madureira, Joana; Kim, Ho; Lee, Whanhee; Tobias, Aurelio; Íñiguez, Carmen; Guo, Yue Leon; Pan, Shih-Chun; Zanobetti, Antonella; Dang, Tran Ngoc; Van Dung, Do; Geiger, Tobias; Otto, Christian; Johnson, Amanda; Hales, Simon; Yu, Pei; Yang, Zhengyu; Ritchie, Elizabeth A.; Guo, YumingBackground: 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.
- Global short-term mortality risk and burden associated with tropical cyclones from 1980 to 2019: a multi-country time-series studyPublication . Huang, Wenzhong; Li, Shanshan; Vogt, Thomas; Xu, Rongbin; Tong, Shilu; Molina, Tomás; Masselot, Pierre; Gasparrini, Antonio; Armstrong, Ben; Pascal, Mathilde; Royé, Dominic; Sheng Ng, Chris Fook; Vicedo-Cabrera, Ana Maria; Schwartz, Joel; Lavigne, Eric; Kan, Haidong; Goodman, Patrick; Zeka, Ariana; Hashizume, Masahiro; Diaz, Magali Hurtado; Valencia, César De la Cruz; Seposo, Xerxes; Nunes, Baltazar; Madureira, Joana; Kim, Ho; Lee, Whanhee; Tobias, Aurelio; Íñiguez, Carmen; Guo, Yue Leon; Pan, Shih-Chun; Zanobetti, Antonella; Dang, Tran Ngoc; Dung, Do Van; Geiger, Tobias; Otto, Christian; Johnson, Amanda; Hales, Simon; Pei Yu; Yang, Zhengyu; Ritchie, Elizabeth A.; Guo, YumingBackground: 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.
- Epidemiology and genetic diversity of invasive Neisseria meningitidis strains circulating in Portugal from 2003 to 2020Publication . Bettencourt, Célia; Nunes, Alexandra; Nogueira, Paulo; Duarte, Sílvia; Silva, Catarina; Gomes, João Paulo; Simões, Maria JoãoInvasive meningococcal disease (IMD) continues to be a public health problem due to its epidemic potential, affecting mostly children. We aimed to present a detailed description of the epidemiology of IMD in Portugal, including insights into the genetic diversity of Neisseria meningitidis strains. Epidemiological analysis included data from the Portuguese National Reference Laboratory of Neisseria meningitidis during 2003 to 2020. Since 2012, N. meningitidis isolates have also been assessed for their susceptibility to antibiotics and were characterized by whole genome sequencing. During 2003–2020, 1392 confirmed cases of IMD were analyzed. A decrease in the annual incidence rate was observed, ranging from 1.99 (2003) to 0.39 (2020), with an average case fatality rate of 7.1%. Serogroup B was the most frequent (69.7%), followed by serogroups C (9.7%), Y (5.7%), and W (2.6%). Genomic characterization of 329 isolates identified 20 clonal complexes (cc), with the most prevalent belonging to serogroup B cc41/44 (26.3%) and cc213 (16.3%). Isolates belonging to cc11 were predominantly from serogroups W (77.3%) and C (76.5%), whereas cc23 was dominant from serogroup Y (65.7%). Over the past 4 years (2017–2020), we observed an increasing trend of cases assigned to cc213, cc32, and cc11. Regarding antimicrobial susceptibility, all isolates were susceptible to ceftriaxone and 61.8% were penicillin-nonsusceptible, whereas 1.4% and 1.0% were resistant to ciprofloxacin and rifampicin. This is the first detailed study on the epidemiology and genomics of invasive N. meningitidis infections in Portugal, providing relevant data to public health policy makers for a more effective control of this disease.
- Health beliefs and attitudes toward Influenza and COVID-19 vaccination in Portugal: a study using a mixed-method approachPublication . Santos, Ana João; Kislaya, Irina; Matias-Dias, Carlos; Machado, AusendaIntroduction: Vaccination is one of the most effective population strategies to prevent infectious diseases and mitigate pandemics, and it is important to understand vaccine uptake determinants since vaccine hesitancy has been increasing for the past few decades. The Health Belief Model (HBM) has been widely used for understanding vaccination behavior. The current study aimed to assess influenza vaccine (IV) non-uptake and attitudes toward COVID-19 vaccination, two important respiratory diseases with similar symptoms, and routes of transmission in the Portuguese population. Methods: We conducted a cross-sectional study using a panel sample of randomly chosen Portuguese households. A total of 1,050 individuals aged 18 years and over responded to a telephone or online questionnaire. Through a mixed-method approach, we employed thematic content analysis to describe reasons for not taking the IV, considering the HBM dimensions, and quantitative statistical analysis to estimate IV and COVID-19 vaccine coverage. Results: The IV uptake for the overall population was 30.7% (CI 95%: 26.5, 35.2). Susceptibility was found to be a main factor for IV non-uptake, followed by barriers, such as stock availability and fear of adverse effects. The uptake of the COVID-19 vaccine was very high in the study population (83.1%, CI 95%: 13.6%−20.9%). There was a high perception of COVID-19-associated severity and fear of the consequences. Individuals who reported IV uptake seemed to perceive a higher severity of COVID-19 and a higher benefit of taking the COVID-19 vaccine for severe complications. Discussion: Thus, the population does not seem to consider influenza to be a health risk, as opposed to COVID-19, which is considered to be a possibly severe disease. The association between IV uptake and COVID-19 perceptions highlights that an overall attitude toward vaccination in general may be an important individual determinant.
- Relative vaccine effectiveness against COVID-19 hospitalisation in persons aged ≥ 65 years: results from a VEBIS network, Europe, October 2021 to July 2023Publication . Fontán-Vela, Mario; Kissling, Esther; Nicolay, Nathalie; Braeye, Toon; Van Evercooren, Izaak; Holm Hansen, Christian; Emborg, Hanne-Dorthe; Fabiani, Massimo; Mateo-Urdiales, Alberto; AlKerwi, Ala'a; Schmitz, Susanne; Castilla, Jesús; Martínez-Baz, Iván; de Gier, Brechje; Hahné, Susan; Meijerink, Hinta; Starrfelt, Jostein; Nunes, Baltazar; Caetano, Constantino; Derrough, Tarik; Nardone, Anthony; Monge, Susana; VEBIS-Lot 4 working groupSince 2021, the Vaccine Effectiveness, Burden and Impact Studies of coronavirus disease 2019 (COVID-19) and influenza (VEBIS) project monitors vaccine effectiveness (VE) in real-world conditions to inform vaccination programmes in the European Union/European Economic Area (EU/EEA) countries [1]. One project aims to monitor real-time COVID-19 VE using electronic health registries (EHR) in multiple countries, with initial findings previously published [2-4]. We report pooled VE results against hospitalisation due to COVID-19 by number of doses received and time since vaccination in a community-dwelling resident population aged ≥ 65 years between October 2021 and July 2023.
- Characterization of a cohort of Angolan children with sickle cell anemia treated with hydroxyureaPublication . Santos, Brígida; Ginete, Catarina; Gonçalves, Elisângela; Delgadinho, Mariana; Miranda, Armandina; Faustino, Paula; Arez, Ana Paula; Brito, MiguelBackground: Sickle Cell Anemia (SCA) is a monogenic disease, although its severity and response to treatment are very heterogeneous. Objectives: This study aims to characterize a cohort of Angolan children with SCA and evaluate their response to hydroxyurea (HU) treatment and the potential side effects and toxicity. Methods: The study enrolled 215 patients between 3 and 12 years old before and after the administration of HU, at a fix dose of 20 mg/kg/day for 12 months. Results: A total of 157 patients started HU medication and 141 of them completed the 12-month treatment. After initiating HU treatment, the frequency of clinical events decreased (transfusions 53.4 %, hospitalizations 47.1 %). The response to HU medication varied among patients, with some experiencing an increase in fetal hemoglobin (HbF) of <5 %. The mean increase in HbF was 11.9 %, ranging from 1.8 % to 31 %. Responders to HU treatment were 57 %, inadequate responders 38.7 % and non-adherent 4.2 %. No clinical side effects related to HU were reported. Hematological toxicities were transient and reversible. Children naïve to HU and with lower HbF reported higher number of hospitalizations caused by malaria infection. During HU treatment, the frequency of malaria episodes did not appear to be affected by HbF levels. Conclusions: the present study provided a valuable contribution to the understanding of the clinical and laboratory profiles of Angolan children with SCA. These findings support the evidence that the implementation of prophylactic measures and treatment with HU is associated with increased survival in children with SCA.
- Strengthening the genomic surveillance of Francisella tularensis by using culture-free whole-genome sequencing from biological samplesPublication . Isidro, Joana; Escudero, Raquel; Luque-Larena, Juan José; Pinto, Miguel; Borges, Vítor; González-Martín-Niño, Rosa; Duarte, Sílvia; Vieira, Luís; Mougeot, François; Vidal, Dolors; Herrera-Rodríguez, Daniel; Rodríguez-Pastor, Ruth; Herrero-Cófreces, Silvia; Jubete-Tazo, Fernando; Gomes, João Paulo; Lopes de Carvalho, IsabelIntroduction: Francisella tularensis is a highly infectious bacterium that causes the zoonotic disease tularemia. The development of genotyping methods, especially those based on whole-genome sequencing (WGS), has recently increased the knowledge on the epidemiology of this disease. However, due to the difficulties associated with the growth and isolation of this fastidious pathogen in culture, the availability of strains and subsequently WGS data is still limited. Methods: To surpass these constraints, we aimed to implement a culture-free approach to capture and sequence F. tularensis genomes directly from complex samples. Biological samples obtained from 50 common voles and 13 Iberian hares collected in Spain were confirmed as positive for F. tularensis subsp. holarctica and subjected to a WGS target capture and enrichment protocol, using RNA oligonucleotide baits designed to cover F. tularensis genomic diversity. Results: We obtained full genome sequences of F. tularensis from 13 animals (20.6%), two of which had mixed infections with distinct genotypes, and achieved a higher success rate when compared with culture-dependent WGS (only successful for two animals). The new genomes belonged to different clades commonly identified in Europe (B.49, B.51 and B.262) and subclades. Despite being phylogenetically closely related to other genomes from Spain, the detected clusters were often found in other countries. A comprehensive phylogenetic analysis, integrating 599 F. tularensis subsp. holarctica genomes, showed that most (sub)clades are found in both humans and animals and that closely related strains are found in different, and often geographically distant, countries. Discussion: Overall, we show that the implemented culture-free WGS methodology yields timely, complete and high-quality genomic data of F. tularensis, being a highly valuable approach to promote and potentiate the genomic surveillance of F. tularensis and ultimately increase the knowledge on the genomics, ecology and epidemiology of this highly infectious pathogen.
- Mosquito (Diptera: Culicidae) Fauna of a Zoological Park in an Urban Setting: Analysis of Culex pipiens s.l. and Their BiotypesPublication . Madeira, Sara; Bernardino, Rui; Osório, Hugo Costa; Boinas, FernandoSimple Summary: Mosquitoes are known for being a nuisance but also as important vectors of disease agents that affect not only humans but also animals. Zoological gardens are special places where humans and animals are found in close proximity, and where mosquitoes can also find the conditions required for their life cycle. This can be especially true for zoos located in urban areas. In this study, we characterized, for the first time, the mosquito fauna of Lisbon Zoo, and we found a low mosquito density and diversity. We found an average of 2.4 mosquitos per trap/night, and five different species were identified. The most common species was the northern house mosquito, Culex pipiens, with sympatric occurrence of the two biotypes and their hybrids in most collections. Mosquitoes were present year-round, with activity detected in winter months, in which mosquitoes usually diapause. This co-occurrence and activity during winter can have implications in terms of disease transmission, namely, flavivirus, which can affect both animals and humans.
- Melon peel flour: utilization as a functional ingredient in bakery productsPublication . Silva, M.A.; Albuquerque, T.G.; Alves, R.C.; Oliveira, M.B.P.P.; Costa, H.S.Food by-products are a major concern with a direct impact on the economy, society, and environment. The valorisation of these by-products could be an advantageous approach to face the increase in food waste since it can compromise environmental health and food sustainability. On the other hand, this valorisation would allow the development of new food products with health benefits for the population. Cucumis melo L. is a highly consumed fruit all over the world since it has excellent sensory and nutritional qualities, being also a good source of bioactive compounds. However, its peel and seeds are usually discarded. The aim of this study was to evaluate the potential of melon peel flour as a functional ingredient for innovative food products. For that, two different formulations containing melon peel flour were developed (a biscuit and a muffin) by replacing a conventional flour (wheat flour) in different percentages (50% and 100%, respectively). The nutritional composition, total phenolic content, and antioxidant potential of the developed products were studied, showing a high content of fibre, high levels of phenolic compounds and good sensory acceptability. These results show that it is possible to enrich different foods with melon peel flour in order to improve their nutritional properties, contributing to improving public health, simultaneously valorising a usually rejected by-product, reducing food waste and the environmental impact.