Instituto Nacional de Saúde Doutor Ricardo Jorge
URI permanente desta comunidade:
Navegar
Percorrer Instituto Nacional de Saúde Doutor Ricardo Jorge por Domínios Científicos e Tecnológicos (FOS) "Ciências Médicas::Ciências da Saúde"
A mostrar 1 - 10 de 53
Resultados por página
Opções de ordenação
- 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.
- 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.
- 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.
- Characteristics and incidence trends of adults hospitalized with community-acquired pneumonia in Portugal, pre-pandemicPublication . Carneiro, Joana; Teixeira, Rita; Leite, Andreia; Lahuerta, Maria; Catusse, Julie; Ali, Mohammad; Lopes, SílviaCommunity-acquired pneumonia (CAP) is a major cause of hospitalization that leads to substantial morbidity, mortality, and costs. Evaluating CAP trends over time is important to understand patterns and the impact of public health interventions. This study aims to describe the characteristics and trends in the incidence of adults hospitalized with CAP in Portugal between 2010 and 2018. In this study, we included hospitalization data, prevalence of comorbidities, and population data. CAP hospitalizations of adults (≥18y) living in mainland Portugal discharged from public hospitals were identified using ICD-9-CM or ICD-10-CM codes. Based on previous CAP studies, we selected nine relevant comorbidities. We described the frequency and incidence of CAP hospitalizations per sex, age group, comorbidity, and year of discharge. Trends were explored using Joinpoint regression. We observed 470,545 CAP hospitalizations falling into the 2010-18 period. The majority were males (54.8%) and aged ≥75 years (65.3%). Most often recorded comorbidities were congestive heart failure (26.4%), diabetes (25.5%), and chronic pulmonary disease (19.2%). The Joinpoint regression identified a gradual decline in the incidence rates of CAP hospitalizations for both sexes and all age groups. Of the nine comorbidities selected, seven showed a progressive increase in incidence rates followed by a subsequent decline (all except HIV/AIDS and chronic renal disease). Our findings offer valuable insights for selecting priority groups for public health interventions and design strategies to mitigate the burden of CAP.
- Characterizing stakeholders in cancer primary prevention in European countries: an exploration of challenges and opportunities using a penta-helix frameworkPublication . Roxo, Luis; Carvalho da Silva Santos, Ana João; Girvalaki, Charis; Geantă, Marius; 4P-CAN WP2 study team; Sousa Uva, MafaldaObjectives: Cancer incidence has been increasing in Europe, with stark disparities between Western and Eastern regions. Cancer primary prevention (CPP) is a cost-effective strategy tackling lifestyle and risk factor exposure, but its implementation goes beyond the actions of the governments. This study aims to characterize stakeholders’ role in CPP, using a penta-helix approach, with the objective of shedding a new light in the Iron Curtain of Cancer Cases. Methods: We followed a mixed-methods approach, with quantitative and qualitative data from CPP stakeholders from the public sector, academia/research, private sector, media and civil society. Snowball sampling was used to distribute a survey where participants (n = 110) were asked which sector was the main driver of change, the most proactive and the most influential. Purposive sampling was used for semi-structured interviews (n = 33), where stakeholders were asked about their CPP activities, motivations, barriers and opportunities, and the role of other sectors. Countries were coded as Western or Eastern. Descriptive analysis was used for quantitative data, while thematic analysis was used for qualitative data. Results: The public sector is viewed as the main driver of change, and the most proactive and influential in both Western and Eastern Europe. However, Eastern European countries emphasize the role of other sectors in CPP more strongly. Thematic analysis identified key roles and themes for the public sector (Strategy: “Looking after citizen’s health,” “Making the system work,” “Operational Engagement”), academia/research (Knowledge: “Scientific credibility,” “Diversity of approaches,” “Getting out of the lab,” “Life in academia/research”), private sector (Responsibility: “Profit-oriented,” “Resources and operational activities,” “Ethics and responsibility”), media (Dissemination: “Capacity to reach people,” “Diversity and scope,” “Information and dissemination”) and civil society (Engagement: “Proximity to people,” “Advocacy and voice,” “Do what others do not do”). Although no meaningful differences were identified between Western and Eastern countries, the results highlight opportunities for Eastern countries to reduce regional disparities. Conclusion: Overall, results point to the complementary role of the sectors, emphasizing that involving different stakeholders and promoting adequate collaborations between them is crucial to unravel the full potential of CPP.
- Comparative Analysis of Direct Costs of Cancer and Risk Factors in EuropePublication . Herțeliu, Claudiu; Horobeț, Alexandra; Nerău, Vlad; Paraschiv, Anca (Gherman); Ștefan, George; Volintiru, Clara; Zaharia, Rodica Milena; Geantă, Marius; Boata Azis, Adriana Elena; Popescu, Ramona; Semenov, Viktor; Kriachkova, Lilia; Kuzmanovska, Milica; Carvalho da Silva Santos, Ana João; Boccia, Stefania; Villani, Leonardo; Espina, Carolina; Mileva, Bilyana; Tchalakov, Ivan; Petrov, Ivaylo; Roxo, Luis Filipe de Almeida; Sousa Uva, Mafalda; Loghin, Cornel Radu; Girvalaki, CharisThis study explores the direct costs and risk factors associated with cancer across European Union member states, emphasizing the economic and public health implications. A Cancer Risk Factors Index (CRFI) is developed to quantify and compare the impact of various determinants, including obesity, smoking, alcohol consumption, socioeconomic conditions, and pollution. Using data from Eurostat and other authoritative sources, we analyze the correlation between CRFI scores, healthcare expenditures, and cancer mortality rates. Results reveal significant disparities in cancer risk factors and healthcare investments across countries, with lower CRFI scores generally associated with higher healthcare spending and improved outcomes. The findings underscore the importance of comprehensive public health strategies and targeted interventions to address modifiable risk factors, reduce cancer-related mortality, and promote equitable healthcare access.