Instituto Nacional de Saúde Doutor Ricardo Jorge
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Percorrer Instituto Nacional de Saúde Doutor Ricardo Jorge por Domínios Científicos e Tecnológicos (FOS) "Ciências Médicas::Ciências da Saúde"
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- 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.
- 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.
- Assessment of genotoxicity biomarkers in the scope of a human biomonitoring study in workers from E-waste management industriesPublication . Lopes Rosário, Rita Isabel; Silva, Maria João; Pina Martins, FranciscoElectrical and electronic waste (e-waste) represents a pressing global challenge with its rapid growth and hazardous composition. This recycling sector often involves inadequate worker safety, exposing e-workers to harmful substances like heavy metals and flame retardants via several routes, causing significant short- and long-term health risks. Human Biomonitoring (HBM) is a useful tool in assessing exposure and associated health outcomes through biomarkers like micronucleus (MN) in blood or epithelial cells, enabling the identification of early biological changes and linking exposure to disease. This HBM study used two assays,- the Buccal Micronucleus Cytome (BMNCyt) assay and the Cytokinesis-Block Micronucleus Cytome (CBMNCyt) assay,- to assess potential genotoxic effects from occupational e-waste exposure. The BMNCyt assay, conducted under the HBM4EU initiative, targets buccal mucosa epithelial cells, a primary barrier against hazardous agents, thus assessing local genotoxic effects. The CBMNCyt assay in peripheral blood lymphocytes, conducted under the PARC Project, reliably measures structural and numerical chromosomal changes, reflecting a systemic effect. This research aimed to assess early biological effects from exposure to pollutants from e-waste in in PBL and buccal epithelial cells of European e-waste workers, comparatively with control groups. The BMNCyt assay showed no significant differences in MN frequency between the exposed and control groups, while the CBMNCyt assay detected significantly increased frequencies of MN in exposed compared with non-exposed groups. Factors like small sample sizes, interindividual differences, and the use of protective equipment might have influenced results. Demographic/lifestyle variables showed differing impacts on MN formation between assays, but also potential influence, thus the importance of their consideration. Concluding, expanding e-waste occupational health research to include more workers/activities within the waste management industry and broader biomonitoring efforts is paramount. Boosting the understanding of health risks associated with those activities will help developing protective measures and mitigation strategies to safeguard the exposed workers’ health.
- Associação entre o Índice de Vulnerabilidade à Pobreza Energética e os Níveis de Tensão Arterial na População PortuguesaPublication . Rodrigues, Madalena; Gouveia, João Pedro; Sousa-Uva, MafaldaEm Portugal, estima-se que entre 1,8 e 3 milhões de pessoas vivam em situação de pobreza energética, estando entre 609 mil e 660 mil em condição severa. A exposição a temperaturas extremas dentro das habitações pode agravar problemas de saúde existentes e aumentar o risco de doenças cardiovasculares, como a hipertensão arterial, que afeta cerca de 36% da população portuguesa entre 25 e 74 anos. A pobreza energética resulta da combinação de baixos rendimentos, má eficiência energética das habitações e dificuldades no pagamento das faturas de energia. Este problema é intensificado pelas alterações climáticas, que elevam a frequência de eventos extremos. Apesar das preocupações expressas em políticas europeias, poucos estudos populacionais avaliaram a associação entre pobreza energética e saúde utilizando medidas objetivas. Este trabalho tem como objetivo estimar a associação entre o Índice de Vulnerabilidade à Pobreza Energética (IVPE) desenvolvido ao nível da freguesia (#3092) e os níveis de tensão arterial na população adulta portuguesa. Trata-se de um estudo epidemiológico, observacional, transversal e analítico, com dados do Inquérito Nacional de Saúde com Exame Físico 2015 (INSEF), abrangendo 4911 indivíduos de 25 a 74 anos. O IVPE foi categorizado em tercis (baixo, médio e alto) e as associações foram analisadas por regressão linear, ajustada para fatores sociodemográficos e económicos. Os resultados evidenciam que viver em áreas com elevada vulnerabilidade à pobreza energética está associado a um aumento significativo da tensão arterial. No contexto do arrefecimento, observou-se um acréscimo de 2,28% na Tensão Arterial Sistólica (TAS) e de 2,08% na Tensão Arterial Diastólica (TAD), enquanto para o aquecimento verificou-se um aumento significativo na TAS, mas sem relevância na TAD. Estes reforçam a pobreza energética como um fator de risco relevante para a saúde, sublinhando a necessidade de políticas públicas eficazes para mitigar os seus impactos. Num contexto de alterações climáticas e envelhecimento da população portuguesa, garantir condições habitacionais adequadas pode ser uma estratégia essencial para reduzir desigualdades sociais, promover a saúde e o bem-estar, bem como aliviar a pressão sobre os sistemas de saúde pública.
- Attainment of global diabetes targets in 2021: a pooled analysis of individual-level data from national surveys in 100 low-income, middle-income, and high-income countriesPublication . Global Health and Population Project on Access to Care for Cardiometabolic Diseases CollaboratorsBackground: WHO launched the Global Diabetes Compact in 2021 to improve worldwide diabetes outcomes by scaling up access to comprehensive, affordable, and high-quality care. This initiative established population diabetes metrics and targets for countries to attain by 2030, namely, 80% of all people with diabetes are diagnosed; and, among people with diagnosed diabetes, 80% have good glycaemic control (HbA1c <8·0%), 80% have good blood pressure control (<140/90 mm Hg), and 60% of people older than 40 years use statins. We aimed to estimate attainment of global diabetes targets worldwide and across country and individual characteristics in 2021. Methods: We analysed pooled, individual participant data from nationally representative household health surveys done in 100 low-income, middle-income, and high-income countries between 2010 and 2023. The sample included non-pregnant adults aged 30-69 years. Diabetes was defined as use of glucose-lowering medications or biochemical evidence of diabetes (fasting plasma glucose ≥7·0 mmol/L or HbA1c ≥6·5% [48 mmol/mol]). The primary outcomes were the proportion of people attaining each diabetes metric. We analysed data using hierarchical Bayesian logistic regression models with the survey year set to 2021. We estimated the age-standardised proportion attaining each metric across the pooled dataset, by country-level characteristics such as World Bank income group, by country, and by individual-level characteristics including age, sex, educational attainment, and BMI. Findings: In 2021, across the pooled dataset, the age-standardised proportion of people with diabetes who had been diagnosed was 63·2% (95% CI 61·8-64·6). Among those diagnosed, 63·2% (62·1-64·4) achieved glycaemic control (HbA1c <8·0%), 70·8% (69·8-71·9) achieved blood pressure control (<140/90 mm Hg), and 31·8% (30·4-33·2) were using statins. Of the 100 included countries, eight met the target for diabetes diagnosis, seven met the target for glycaemic control, 15 met the target for blood pressure control, and eight met the target for statin use. By country income group, the age-standardised proportion of people with diabetes who had been diagnosed ranged from 35·3% (33·5-37·1) in low-income countries to 69·9% (68·3-71·5) in high-income countries. Among those with diagnosed diabetes, glycaemic control ranged from 56·0% (54·2-57·8) in lower-middle-income countries to 73·7% (72·7-74·6) in high-income countries; blood pressure control ranged from 58·3% (57·3-59·4) in lower-middle-income countries to 82·4% (81·4-83·4) in high-income countries; and statin use ranged from 9·7% (8·0-11·4) in low-income countries to 58·7% (57·4-59·9) in high-income countries. Across individual-level characteristics, patterns of inequities were observed in the attainment of each metric. Interpretation: There are pronounced inequities at multiple levels in the attainment of global diabetes metrics. Substantial progress is needed to reduce inequities and to achieve the 2030 targets.
- Baseline data and associations between urinary biomarkers of polycyclic aromatic hydrocarbons, blood pressure, hemogram, and lifestyle among wildland firefightersPublication . Barros, Bela; Paiva, Ana Margarida; Oliveira, Marta; Alves, Sara; Esteves, Filipa; Fernandes, Adília; Vaz, Josiana; Slezakova, Klara; Costa, Solange; Teixeira, João Paulo; Morais, SimoneIntroduction: Available literature has found an association between firefighting and pathologic pathways leading to cardiorespiratory diseases, which have been linked with exposure to polycyclic aromatic hydrocarbons (PAHs). PAHs are highlighted as priority pollutants by the European Human Biomonitoring Initiative in occupational and non-occupational contexts. Methods: This cross-sectional study is the first to simultaneously characterize six creatinine-adjusted PAHs metabolites (OHPAHs) in urine, blood pressure, cardiac frequency, and hemogram parameters among wildland firefighters without occupational exposure to fire emissions (> 7 days), while exploring several variables retrieved via questionnaires. Results: Overall, baseline levels for total OHPAHs levels were 2 to 23-times superior to the general population, whereas individual metabolites remained below the general population median range (except for 1-hydroxynaphthalene+1-hydroxyacenaphtene). Exposure to gaseous pollutants and/or particulate matter during work-shift was associated with a 3.5-fold increase in total OHPAHs levels. Firefighters who smoke presented 3-times higher total concentration of OHPAHs than non-smokers (p < 0.001); non-smoker females presented 2-fold lower total OHPAHs (p = 0.049) than males. 1-hydroxypyrene was below the recommended occupational biological exposure value (2.5 μg/L), and the metabolite of carcinogenic PAH (benzo(a)pyrene) was not detected. Blood pressure was above 120/80 mmHg in 71% of subjects. Firefighters from the permanent intervention team presented significantly increased systolic pressure than those who performed other functions (p = 0.034). Tobacco consumption was significantly associated with higher basophils (p = 0.01–0.02) and hematocrit (p = 0.03). No association between OHPAHs and blood pressure was found. OHPAHs concentrations were positively correlated with monocyte, basophils, large immune cells, atypical lymphocytes, and mean corpuscular volume, which were stronger among smokers. Nevertheless, inverse associations were observed between fluorene and pyrene metabolites with neutrophils and eosinophils, respectively, in non-smokers. Hemogram was negatively affected by overworking and lower physical activity. Conclusion: This study suggests possible associations between urinary PAHs metabolites and health parameters in firefighters, that should be further assessed in larger groups.
- Biomonitoring of firefighters’ exposure to priority pollutant metal(loid)s during wildland fire combat missions: Impact on urinary levels and health risksPublication . Paiva, Ana Margarida; Barros, Bela; Azevedo, Rui; Oliveira, Marta; Alves, Sara; Esteves, Filipa; Fernandes, Adília; Vaz, Josiana; Alves, Maria José; Slezakova, Klara; Pereira, Maria do Carmo; Teixeira, João Paulo; Costa, Solange; Almeida, Agostinho; Morais, SimoneWildland firefighters are exposed to metal(loid)s released during wildfires through vegetation combustion, which also promotes remobilization of accumulated anthropogenic metal(loid)s. Studies biomonitoring metal(loid)s exposure promoted exclusively by wildfire suppression activities are lacking. This work aimed to characterize, for the first time, the impact of real-life wildland firefighting operations on urinary levels of priority pollutant metal(loid)s [14 included in ATSDR, 11 in USEPA, and 4 in Human Biomonitoring for Europe Initiative priority lists] in firefighters. Spot urines were sampled pre-exposure (105 non-smokers, 76 smokers) and post-exposure to firefighting activities (20 non-smokers, 25 smokers); among those, paired samples were collected from 14 non-smoking and 24 smoking firefighters. Smokers displayed significantly higher baseline levels of zinc (28 %), lithium (29 %), cadmium (55 %), rubidium (13 %), and copper (20 %) than non-smokers. Following wildfire suppression, the concentration of the WHO potentially toxic metal(loid)s rose from 2 % to 3 % in smokers and 2 % to 5 % in non-smokers (up to 4 % for all firefighters and up to 5 % in paired samples). Levels of nickel (33-53 %), antimony (45-56 %), and cesium (40-47 %) increased significantly post-exposure in non-smokers (in all firefighters and in paired samples), whose urinary concentrations were generally more impacted by wildfire emissions than those of smokers. Arsenic (80 %) displayed the only significant increase post-exposure in smokers, being the best discriminant of exposure to wildfire emissions in these subjects. Significant positive correlations were found for age and/or career length with cadmium, lead, barium, strontium, and mercury, and for body mass index with arsenic. The reference/guidance values were exceeded for arsenic, zinc, cesium, nickel, antimony, cadmium, lead, thallium, mercury, copper, and cobalt in 1-90 % of firefighters suggesting augmented health risks due to wildfire combating and emphasizing the need of mitigation strategies. This study also provides biomonitoring data to help setting reference values for the occupationally exposed part of population.
- Biomonitoring of polycyclic aromatic hydrocarbons exposure and short-time health effects in wildland firefighters during real-life fire eventsPublication . Paiva, Ana Margarida; Barros, Bela; Oliveira, Marta; Alves, Sara; Esteves, Filipa; Fernandes, Adília; Vaz, Josiana; Slezáková; Teixeira, João Paulo; Costa, Solange; Morais, SimoneHuman biomonitoring data retrieved from real-life wildland firefighting in Europe and, also, worldwide are scarce. Thus, in this study, 176 Portuguese firefighters were biomonitored pre- and post- unsimulated wildfire combating (average:12-13 h; maximum: 55 h) to evaluate the impact on the levels of urinary polycyclic aromatic hydrocarbons hydroxylated metabolites (OHPAH; quantified by high-performance liquid chromatography with fluorescence detection) and the associated short-term health effects (symptoms, and total and differentiated white blood cells). Correlations between these variables and data retrieved from the self-reported questionnaires were also investigated. Firefighters were organized into four groups according to their exposure to wildfire emissions and their smoking habits: non-smoking non-exposed (NSNExp), non-smoking exposed (NSExp), smoking non-exposed (SNExp), and smoking and exposed (SExp). The most abundant metabolites were 1-hydroxynaphthalene and 1-hydroxyacenaphthene (1OHNaph + 1OHAce) (98-99 %), followed by 2-hydroxyfluorene (2OHFlu) (0.2-1.1 %), 1-hydroxyphenanthrene (1OHPhen) (0.2-0.4 %), and 1-hydroxypyrene (1OHPy) (0.1-0.2 %); urinary 3-hydroxybenzo(a)pyrene was not detected. The exposure to wildfire emissions significantly elevated the median concentrations of each individual and total OHPAH compounds in all groups, but this effect was more pronounced in non-smoking (1.7-4.2 times; p ≤ 0.006) than in smoking firefighters (1.3-1.6 times; p ≤ 0.03). The greatest discriminant of exposure to wildfire emissions was 1OHNaph + 1OHAce (increase of 4.2 times), while for tobacco smoke it was 2OHFlu (increase of 10 times). Post-exposure, white blood cells count significantly increased ranging from 1.4 (smokers, p = 0.025) to 3.7-fold (non-smokers, p < 0.001), which was accompanied by stronger significant correlations (0.480 < r < 0.882; p < 0.04) between individual and total OHPAH and total white blood cells (and lymphocytes > monocytes > neutrophils in non-smokers), evidencing the impact of PAH released from wildfire on immune cells. This study identifies Portuguese firefighters with high levels of biomarkers of exposure to PAH and points out the importance of adopting biomonitoring schemes, that include multiple biomarkers of exposure and biomarkers of effect, and implementing mitigations strategies.
- Cancer Prevention Literacy Questionnaire (CPL-Q): development and validation within the World Code Against Cancer FrameworkPublication . Feliu, Ariadna; Islam, Rubana; Romeo-Cervera, Paula; Bouaoun, Liacine; Whitelock, Victoria; Pirvan, Mirela; Roxo, Luis; Carvalho da Silva Santos, Ana João; Espina, CarolinaBackground: Health literacy is a key determinant of health, shaping individuals ability to understand and act on health information. Low cancer literacy is associated with fatalistic beliefs and reduced participation in prevention and screening programmes. Although around 40% of all cancers are preventable, public awareness of modifiable risk factors remains low. The European Code Against Cancer (ECAC), developed under the World Code Against Cancer Framework, aims to strengthen prevention knowledge; however, tools to measure cancer prevention literacy, and therefore evaluate its impact, are lacking. This study aimed to develop and validate a questionnaire to assess ‘cancer prevention literacy’ in adults from the general population. Methods: We conducted a methodological study to develop a questionnaire measuring ‘cancer prevention literacy’ in adults from the general population using the Integrative Model of Behavioural Prediction as theoretical framework. Questionnaire development followed a three-stage process: (1) a literature review and two-round Delphi process to select and refine items; (2) a third Delphi round, complemented by readability checks, face-validity assessment, and cognitive testing to evaluate item relevance, clarity, and representativeness; and (3) a pre-test and psychometric analysis to assess construct validity. Results: The final Cancer Prevention Literacy Questionnaire (CPL-Q) consists of a 10-question validated instrument comprising 58 items, with selected items incorporating the verbatim wording of the recommendations from the ECAC, 4th edition. Strong expert agreement was achieved through an iterative Delphi process, and content and face validity indicated that the items were comprehensible, relevant, and appropriate. Psychometric analyses, including exploratory and confirmatory factor analysis, provide preliminary support for the instrument’s construct validity, with initial evidence suggesting acceptable reliability. Conclusion: The CPL-Q provides a standardised instrument to measure ‘cancer prevention literacy’ and to assess the impact of Regional Codes Against Cancer through monitoring and benchmarking changes over time. It also offers a practical tool to identify gaps in ‘cancer prevention literacy’ within specific populations and to support international comparisons and longitudinal evaluations, thereby contributing to the evidence base for cancer prevention policies.
- CCL2 expression predicts clinical outcomes and regulates E-cadherin and angiogenesis in pituitary tumoursPublication . Silva, Ana Luísa; Barry, Sayka; Lopes-Pinto, Mariana; Joaquim, Rita; Miranda, Catarina; Reis, Fábio; Miranda, Micaella; Matos, Paulo; Suleyman, Oniz; Oliveira, Tiago; López-Presa, Dolores; Borrecho, Gonçalo; Tortosa, Francisco; Faria, Claúdia C.; Korbonits, Márta; Marques, PedroThe crosstalk between tumour cells and microenvironment components in pituitary neuroendocrine tumours (PitNETs), including chemokines, may impact tumour behaviour and clinical outcomes. CCL2 was previously identified as a key chemokine in PitNETs, but its role remains unknown. We aimed to study the role of CCL2 in defining the phenotype and clinical outcomes of PitNETs and in regulating macrophage chemotaxis, epithelial-to-mesenchymal transition (EMT) and angiogenesis. We studied CCL2 and E-cadherin expression, macrophages (CD68 and CD163) and vessels (CD31) in samples from 86 PitNET patients. Higher CCL2 mRNA expression was found in patients who required multimodal and multiple treatments and had active disease at the last follow-up. Higher CCL2 immunoreactivity was observed in patients with larger PitNETs. Among somatotroph tumours, CCL2 mRNA expression correlated with serum IGF-1 at the last follow-up. CCL2 mRNA expression levels correlated negatively with CDH1 expression and with E-cadherin complete membranous staining. In vitro, CCL2 downregulated E-cadherin expression in GH3 cells but did not affect cell morphology or migration. CCL2 expression correlated with the number of vessels, vessel perimeter and vessel area in PitNETs but not with PitNET-infiltrating macrophages. Our data suggest that CCL2 may lead to (or is at least a predictive marker of) poorer clinical outcomes and more difficult-to-treat PitNETs, potentially through its regulatory effects on different tumour-related mechanisms beyond immune cell chemotaxis, including in the activation of the EMT pathway and modulation of angiogenesis in PitNETs. Further studies are needed to corroborate our findings and to validate CCL2 as a potential predictive marker and therapeutic target in PitNETs.