Instituto Nacional de Saúde Doutor Ricardo Jorge
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- Abordagem da obesidade infantil através do Objetivo de Desenvolvimento Sustentável 3 – Saúde e Bem-Estar : a contribuição do Centro Colaborativo da OMS para Nutrição e Obesidade InfantilPublication . Rito, Ana; Gaspar, Marta; Alvito, Paula; Bento, Alexandra; Santos, Cristina AbreuA obesidade infantil constitui um dos maiores desafios de saúde pública do século XXI e representa uma ameaça significativa para o cumprimento do Objetivo de Desenvolvimento Sustentável 3 (ODS 3) – Saúde e Bem-Estar, definido pela Agenda 2030 das Nações Unidas. Este artigo analisa criticamente a relação entre a obesidade infantil e o ODS3, com especial enfoque no papel desempenhado pelo Instituto Nacional de Saúde Doutor Ricardo Jorge (INSA), enquanto Centro Colaborativo da Organização Mundial da Saúde (OMS) para Nutrição e Obesidade Infantil (CCOMS). Foi realizada uma revisão da literatura científica publicada entre 2020 e 2025, tendo sido identificadas 379 publicações das quais 19 artigos científicos sujeitos a arbitragem por pares foram incluídos na análise final. Seis estudos forneceram evidência direta sobre a relação entre obesidade infantil e o ODS 3, com particular ênfase na meta 3.4, evidenciando a obesidade infantil como fator determinante nas doenças não transmissíveis sublinhando a relevância de dados epidemiológicos e reforçando a necessidade de estratégias intersetoriais e prevenção e promoção da saúde. Os resultados destacaram ainda a escassez de literatura abrangente que articule soluções sustentáveis para a obesidade infantil em consonância com as metas do ODS 3. O CCOMS enquanto centro de vigilância nutricional infantil (com destaque para o estudo “Childhood Obesity Surveillance Initiative” (COSI) da OMS Europa), pelo seu apoio técnico e ação multissetorial e participação ativa na investigação e inovação científica, tem vindo a reforçar substancialmente o progresso em direção às metas do ODS 3. Em Portugal, os dados recentes do COSI revelam prevalências preocupantes de excesso de peso (31,9%) e obesidade (13,5%) em crianças, confirmando a urgência de medidas eficazes. Conclui-se que enfrentar a obesidade infantil é crucial para reduzir desigualdades em saúde e avançar no cumprimento do ODS 3, exigindo colaboração internacional e nacional, políticas públicas integradas e intervenções baseadas em evidência científica.
- Acrilamida em cereais e derivados: validação do método analítico e resultados preliminaresPublication . Copeto, Sandra; Jesus, Susana; Delgado, Inês; Coelho, InêsA reação de Maillard, responsável pela cor, sabor e aroma dos alimentos, também produz substâncias nocivas, como a acrilamida (AA). Esta amida insaturada forma-se quando alimentos ricos em hidratos de carbono, como pão, batatas e café, são cozinhados a temperaturas elevadas e humidade baixa. A União Europeia classificou a AA como carcinogénica (Categoria 1B), mutagénica (Categoria 1B) e tóxica para a reprodução (Categoria 2). O presente estudo visa validar um método para determinar AA em cereais e derivados e investigar a sua presença em diferentes variedades desses produtos. Utilizou-se a cromatografia líquida de ultra eficiência acoplada a um detetor de massa (UPLC-MS/MS) com ionização por electrospray positiva (ESI+ ) para detetar e quantificar a AA. O desempenho do método foi validado utilizando testes de avaliação externa da qualidade internacionais como testes de proficiência (FAPAS) e material de referência certificado (ERM-BD272). Avaliaram-se parâmetros como linearidade, limite de deteção (LD), limite de quantificação (LQ), precisão, exatidão e incerteza. Os LD e LQ foram de 0,40 µg/L e 1,22 µg/L, respetivamente, em conformidade com o Regulamento (UE) 2017/2158. A curva de calibração mostrou linearidade (R2 > 0,995). O método apresentou boas taxas de recuperação (92%-105%) e de precisão (desvio padrão relativo (RSD) ≤ 13%), participação satisfatória em ensaios de comparação interlaboratorial (ECI) (Z-score: 0,69 para Crispbread e -0,93 para Biscuit), assim como bons resultados para o ERM-BD272, demonstrando que o método é adequado para a determinação de AA em cereais e derivados. O método foi aplicado a cereais e derivados existentes no mercado, incluindo bolacha Maria, pão de trigo, flocos de milho e bolachas para bebé, todos recolhidos em Lisboa, Portugal. Os resultados de AA das amostras avaliadas, expressos em µg/kg, encontram-se abaixo dos valores legislados pelo Regulamento (EU) 2017/2158. Embora os níveis de acrilamida encontrados cumpram os limites estabelecidos pela União Europeia, é necessária uma monitorização contínua da sua ocorrência, considerando as incertezas ainda presentes sobre os efeitos a longo prazo deste contaminante.
- Acute venous thromboembolism plasma and red blood cell metabolomic profiling reveals potential new early diagnostic biomarkers: observational clinical studyPublication . Febra, Claúdia; Saraiva, Joana; Vaz, Fátima; Soares, Nelson; Penque, PenqueBackground: Venous thromboembolism (VTE) is a leading cause of cardiovascular mortality. The diagnosis of acute VTE is based on complex imaging exams due to the lack of biomarkers. Recent multi-omics based research has contributed to the development of novel biomarkers in cardiovascular diseases. Our aim was to determine whether patients with acute VTE have differences in the metabolomic profile compared to non-acute VTE. Methods: This observational trial included 62 patients with clinical suspicion of acute deep vein thrombosis or pulmonary embolism, admitted to the emergency room. There were 50 patients diagnosed with acute VTE and 12 with non-acute VTE conditions and no significant differences were found between the two groups for clinical and demographic characteristics. Metabolomics assays identified and quantified a final number of 91 metabolites in plasma and 55 metabolites in red blood cells (RBCs). Plasma from acute VTE patients expressed tendency to a specific metabolomic signature, with univariate analyses revealing 23 significantly different molecules between acute VTE patients and controls (p < 0.05). The most relevant metabolic pathway with the strongest impact on the acute VTE phenotype was D-glutamine and D-glutamate (p = 0.001, false discovery rate = 0.06). RBCs revealed a specific metabolomic signature in patients with a confirmed diagnosis of DVT or PE that distinguished them from other acutely diseased patients, represented by 20 significantly higher metabolites and four lower metabolites. Three of those metabolites revealed high performant ROC curves, including adenosine 3',5'-diphosphate (AUC 0.983), glutathione (AUC 0.923), and adenine (AUC 0.91). Overall, the metabolic pathway most impacting to the differences observed in the RBCs was the purine metabolism (p = 0.000354, false discovery rate = 0.68). Conclusions: Our findings show that metabolite differences exist between acute VTE and nonacute VTE patients admitted to the ER in the early phases. Three potential biomarkers obtained from RBCs showed high performance for acute VTE diagnosis. Further studies should investigate accessible laboratory methods for the future daily practice usefulness of these metabolites for the early diagnosis of acute VTE in the ER.
- Adapting to COVID-19: Insights from Portuguese residents' home-based lifePublication . Aguiar, Ana; Soares, Patricia; Barbosa, Pedro; Duarte, Raquel; Pinto, MartaBackground: The COVID-19 pandemic led to widespread lockdowns and remote work and educational practices that have impacted the lives of many families. Objective: We aimed to investigate how parents and caregivers altered their routines due to online schooling and teleworking, exploring their association with increased anxiety and depression symptoms. Methods: We conducted an online cross-sectional study and collected data through snowball sampling. We asked questions about age, gender, dwelling area, educational level, and marital status, as well as an open-ended question about teleworking and homeschooling - "Did your routine change due to your children being forced to stay home and take online classes? If so, please explain how it has influenced your personal and professional life, both positively and negatively". Thematic analysis was used to analyse the responses. Results: A total of 181 respondents, primarily women (72.4%), averaging 36.6 years old, holding bachelor's degrees (44.2%), were included. About 78.5% reported routine adjustments. Four salient themes emerged: 1) Perceived changes in professional and personal life, 2) Perceived changes in learning methods, 3) Mental health issues and 4) Perceived advantages of working from home with children at online school. Regarding mental health, 25.4% exhibited symptoms of anxiety, and 7.7% displayed depression symptoms, predominantly linked (80%) to the pandemic's impact. Conclusion: Family routines were disrupted, causing stress. In future crises, policymakers, public health experts, and researchers must acknowledge these challenges to mitigate negative consequences. Simultaneously, they should focus on strategies that enhance the positive aspects of restrictive measures and related policies.
- Advancements in risk stratification and management strategies in primary cardiovascular preventionPublication . Barkas, Fotios; Sener, Yusuf Ziya; Golforoush, Pelin Arabacilar; Kheirkhah, Azin; Rodriguez-Sanchez, Elena; Novak, Jan; Apellaniz-Ruiz, Maria; Akyea, Ralph Kwame; Bianconi, Vanessa; Ceasovschih, Alexandr; Chee, Ying Jie; Cherska, Mariia; Chora, Joana Rita; D'Oria, Mario; Demikhova, Nadiia; Kocyigit Burunkaya, Duygu; Rimbert, Antoine; Macchi, Chiara; Rathod, Krishnaraj; Roth, Lynn; Sukhorukov, Vasily; Stoica, Svetlana; Scicali, Roberto; Storozhenko, Tatyana; Uzokov, Jamol; Lupo, Maria Giovanna; van der Vorst, Emiel P.C.; Porsch, FlorentinaAtherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality worldwide, highlighting the urgent need for advancements in risk ssessment and management strategies. Although significant progress has been made ecently, identifying and managing apparently healthy individuals at a higher risk of developing atherosclerosis and those with subclinical atherosclerosis still poses significant challenges. Traditional risk assessment tools have limitations in accurately predicting future events and fail to encompass the complexity of the atherosclerosis trajectory. In this review, we describe novel approaches in biomarkers, genetics, advanced imaging techniques, and artificial intelligence that have emerged to address this gap. Moreover, polygenic risk scores and imaging modalities such as coronary artery calcium scoring, and coronary computed tomography angiography offer promising avenues for enhancing primary cardiovascular risk stratification and personalised intervention strategies. On the other hand, interventions aiming against atherosclerosis development or promoting plaque regression have gained attention in primary ASCVD prevention. Therefore, the potential role of drugs like statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, omega-3 fatty acids, antihypertensive agents, as well as glucose-lowering and anti-inflammatory drugs are also discussed. Since findings regarding the efficacy of these interventions vary, further research is still required to elucidate their mechanisms of action, optimize treatment regimens, and determine their long-term effects on ASCVD outcomes. In conclusion, advancements in strategies addressing atherosclerosis prevention and plaque regression present promising avenues for enhancing primary ASCVD prevention through personalised approaches tailored to individual risk profiles. Nevertheless, ongoing research efforts are imperative to refine these strategies further and maximise their effectiveness in safeguarding cardiovascular health.
- Aeromonas spp. in Freshwater Bodies: Antimicrobial Resistance and Biofilm AssemblyPublication . Nascimento, Maria; Rodrigues, João; Matias, Rui; Jordão, LuisaAeromonas spp. are environmental bacteria able to infect animals and humans. Here, we aim to evaluate the role of biofilms in Aeromonas persistence in freshwater. Aeromonas were isolated from water and biofilm samples and identified by Vitek-MS and 16S rRNA sequencing. Antibiotic susceptibility profiles were determined according to EUCAST, and a crystal violet assay was used to assess biofilm assembly. MTT and the enumeration of colony-forming units were used to evaluate biofilm and planktonic Aeromonas susceptibility to chlorination, respectively. Identification at the species level was challenging, suggesting the need to improve the used methodologies. Five different Aeromonas species (A. salmonicida, A. hydrophila, A. media, A. popoffii and A. veronii) were identified from water, and one species was identified from biofilms (A. veronii). A. veronnii and A. salmonicida presented resistance to different antibiotics, whith the highest resistance rate observed for A. salmonicida (multiple antibiotic resistance index of 0.25). Of the 21 isolates, 11 were biofilm producers, and 10 of them were strong biofilm producers (SBPs). The SBPs presented increased tolerance to chlorine disinfection when compared with their planktonic counterparts. In order to elucidate the mechanisms underlying biofilm tolerance to chlorine and support the importance of preventing biofilm assembly in water reservoirs, further research is required.
- Air pollution mixture complexity and its effect on PM2.5-related mortality: A multicountry time-series study in 264 citiesPublication . Masselot, Pierre; Kan, Haidong; Kharol, Shailesh K; Bell, Michelle L.; Sera, Francesco; Lavigne, Eric; Breitner, Susanne; das Neves Pereira da Silva, Susana; Burnett, Richard T.; Gasparrini, Antonio; Brook, Jeffrey R.; MCC Collaborative Research NetworkBackground: Fine particulate matter (PM2.5) occurs within a mixture of other pollutant gases that interact and impact its composition and toxicity. To characterize the local toxicity of PM2.5, it is useful to have an index that accounts for the whole pollutant mix, including gaseous pollutants. We consider a recently proposed pollutant mixture complexity index (PMCI) to evaluate to which extent it relates to PM2.5 toxicity. Methods: The PMCI is constructed as an index spanning seven different pollutants, relative to the PM2.5 levels. We consider a standard two-stage analysis using data from 264 cities in the Northern Hemisphere. The first stage estimates the city-specific relative risks between daily PM2.5 and all-cause mortality, which are then pooled into a second-stage meta-regression model with which we estimate the effect modification from the PMCI. Results: We estimate a relative excess risk of 1.0042 (95% confidence interval: 1.0023, 1.0061) for an interquartile range increase (from 1.09 to 1.95) of the PMCI. The PMCI predicts a substantial part of within-country relative risk heterogeneity with much less between-country heterogeneity explained. The Akaike information criterion and Bayesian information criterion of the main model are lower than those of alternative meta-regression models considering the oxidative capacity of PM2.5 or its composition. Conclusions: The PMCI represents an efficient and simple predictor of local PM2.5-related mortality, providing evidence that PM2.5 toxicity depends on the surrounding gaseous pollutant mix. With the advent of remote sensing for pollutants, the PMCI can provide a useful index to track air quality.
- Alkyl deoxyglycoside-polymyxin combinations against critical priority carbapenem-resistant gram-negative bacteriaPublication . Matos, Ana M. de; Calado, Patrícia; Miranda, Mónica; Almeida, Rita; Rauter, Amélia P.; Oliveira, M. Conceição; Manageiro, Vera; Caniça, ManuelaThe escalating antimicrobial resistance crisis urges the development of new antibacterial treatments with innovative mechanisms of action, particularly against the critical priority carbapenem-resistant Acinetobacter baumannii (CRAB), Pseudomonas aeruginosa (CRPA) and Enterobacteriaceae (CRE). Membrane-disrupting dodecyl deoxyglycosides have been reported for their interesting phosphatidylethanolamine-associated bactericidal activity against Gram-positive strains; however, their inability to penetrate the Gram-negative outer membrane (OM) renders them useless against the most challenging pathogens. Aiming to repurpose alkyl deoxyglycosides against Gram-negative bacteria, this study investigates the antimicrobial effects of five reference compounds with different deoxygenation patterns or anomeric configurations in combination with polymyxins as adjuvants for enhanced OM permeability. The generation of the lead 4,6-dideoxy scaffold was optimized through a simultaneous dideoxygenation step and applied to the synthesis of a novel alkyl 4,6-dideoxy C-glycoside 5, herein reported for the first time. When combined with subtherapeutic colistin concentrations, most glycosides demonstrated potent antimicrobial activity against several multidrug-resistant clinical isolates of CRAB, CRE and CRPA exhibiting distinct carbapenem resistance mechanisms, together with acceptable cytotoxicity against human HEK-293T and Caco-2 cells. The novel 4,6-dideoxy C-glycoside 5 emerged as the most promising prototype structure for further development (MIC 3.1 μg/mL when combined with colistin 0.5 μg/mL against CRPA or 0.25 μg/mL against several CRE and CRAB strains), highlighting the potential of C-glycosylation for an improved bioactive profile. This study is the first to show the potential of IM-targeting carbohydrate-based compounds for the treatment of infections caused by MDR Gram-negative pathogens of clinical importance.
- All-cause, cardiovascular, and respiratory mortality and wildfire-related ozone: a multicountry two-stage time series analysisPublication . Chen, Gongbo; Guo, Yuming; Yue, Xu; Xu, Rongbin; Yu,Wenhua; Ye, Tingting; Tong, Shilu; Gasparrini, Antonio; Bell,Michelle L.; Armstrong, Ben; Schwartz, Joel; Jaakkola, Jouni J.K.; Lavigne, Eric; Saldiva, Paulo Hilario Nascimento; Kan, Haidong; Royé, Dominic; Urban, Aleš; Vicedo-Cabrera, Ana Maria; Tobias, Aurelio; Forsberg, Bertil; Sera, Francesco; Lei, Yadong; Abramson, Michael J.; Li, Shanshan; Abrutzky, Rosana; Alahmad, Barrak; Ameling, Caroline; Åström, Christofer; Breitner, Susanne; Carrasco-Escobar, Gabriel; Coêlho, Micheline de Sousa Zanotti Stagliorio; Colistro, Valentina; Correa, Patricia Matus; Dang, Tran Ngoc; de'Donato, Francesca; Dung, Do Van; Entezari, Alireza; Garcia, Samuel David Osorio; Garland, Rebecca M.; Goodman, Patrick; Guo, Yue Leon; Hashizume, Masahiro; Holobaca, Iulian-Horia; Honda, Yasushi; Houthuijs, Danny; Hurtado-Díaz, Magali; Íñiguez, Carmen; Katsouyanni, Klea; Kim, Ho; Kyselý, Jan; Lee, Whanhee; Maasikmets, Marek; Madureira, Joana; Mayvaneh, Fatemeh; Nunes, Baltazar; Orru, Hans; Ortega, Nicol´s Valdés; Overcenco, Ala; Pan, Shih-Chun; Pascal, Mathilde; Ragettli, Martina S.; Rao, Shilpa; Ryti, Niilo R.I.; Samoli, Evangelia; Schneider, Alexandra; Scovronick, Noah; Seposo, Xerxes; Stafoggia, Massimo; Valencia, César De la Cruz; Zanobetti, Antonella; Zeka, Ariana; behalf of the Multi-Country Multi-City Collaborative Research NetworkBackground: Wildfire activity is an important source of tropospheric ozone (O3) pollution. However, no study to date has systematically examined the associations of wildfire-related O3 exposure with mortality globally. Methods: We did a multicountry two-stage time series analysis. From the Multi-City Multi-Country (MCC) Collaborative Research Network, data on daily all-cause, cardiovascular, and respiratory deaths were obtained from 749 locations in 43 countries or areas, representing overlapping periods from Jan 1, 2000, to Dec 31, 2016. We estimated the daily concentration of wildfire-related O3 in study locations using a chemical transport model, and then calibrated and downscaled O3 estimates to a resolution of 0·25° × 0·25° (approximately 28 km2 at the equator). Using a random-effects meta-analysis, we examined the associations of short-term wildfire-related O3 exposure (lag period of 0-2 days) with daily mortality, first at the location level and then pooled at the country, regional, and global levels. Annual excess mortality fraction in each location attributable to wildfire-related O3 was calculated with pooled effect estimates and used to obtain excess mortality fractions at country, regional, and global levels. Findings: Between 2000 and 2016, the highest maximum daily wildfire-related O3 concentrations (≥30 μg/m3) were observed in locations in South America, central America, and southeastern Asia, and the country of South Africa. Across all locations, an increase of 1 μg/m3 in the mean daily concentration of wildfire-related O3 during lag 0-2 days was associated with increases of 0·55% (95% CI 0·29 to 0·80) in daily all-cause mortality, 0·44% (-0·10 to 0·99) in daily cardiovascular mortality, and 0·82% (0·18 to 1·47) in daily respiratory mortality. The associations of daily mortality rates with wildfire-related O3 exposure showed substantial geographical heterogeneity at the country and regional levels. Across all locations, estimated annual excess mortality fractions of 0·58% (95% CI 0·31 to 0·85; 31 606 deaths [95% CI 17 038 to 46 027]) for all-cause mortality, 0·41% (-0·10 to 0·91; 5249 [-1244 to 11 620]) for cardiovascular mortality, and 0·86% (0·18 to 1·51; 4657 [999 to 8206]) for respiratory mortality were attributable to short-term exposure to wildfire-related O3. Interpretation: In this study, we observed an increase in all-cause and respiratory mortality associated with short-term wildfire-related O3 exposure. Effective risk and smoke management strategies should be implemented to protect the public from the impacts of wildfires.
- Alternative Splicing at the Crossroad of Inflammatory Bowel Diseases and Colitis-Associated Colon CancerPublication . Matos, Paulo; Jordan, PeterSimple Summary: Patients with ulcerative colitis (UC) face a higher risk of developing colorectal cancer (CRC) due to chronic inflammation, a known promoter of tumour growth. Here, we review the molecular differences between colitis-associated cancer (CAC) and sporadic CRC, with a focus on “alternative splicing”, a mechanism by which the same gene can produce various protein forms. We explore how inflammation triggers changes in this process, increasing cancer risk for UC patients. The revised data emphasize that additional research into these molecular changes could help identify new biomarkers (molecules that indicate disease progression) and pave the way for innovative treatments targeting these alterations. Such advances would improve outcomes and quality of life for patients while contributing to cancer prevention and care.