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Browsing INSA - Artigos em revistas internacionais by Field of Science and Technology (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.
- 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.
- COVID-19 vaccine effectiveness in the paediatric population aged 5-17 years: a multicentre cohort study using electronic health registries in six European countries, 2021 to 2022Publication . Soares, Patricia; Machado, Ausenda; Nicolay, Nathalie; Monge, Susana; Sacco, Chiara; Hansen, Christian Holm; Meijerink, Hinta; Martínez-Baz, Iván; Schmitz, Susanne; Humphreys, James; Fabiani, Massimo; Echeverria, Aitziber; AlKerwi, Ala'a; Nardone, Anthony; Mateo-Urdiales, Alberto; Castilla, Jesús; Kissling, Esther; Nunes, Baltazar; VEBIS-Lot 4 working groupBackground: During the first year of the COVID-19 pandemic, vaccination programmes targeted children and adolescents to prevent severe outcomes of SARS-CoV-2 infection. Aim: To estimate COVID-19 vaccine effectiveness (VE) against hospitalisation due to COVID-19 in the paediatric population, among those with and without previously documented SARS-CoV-2 infection. Methods: We established a fixed cohort followed for 12 months in Denmark, Norway, Italy, Luxembourg, Navarre (Spain) and Portugal using routine electronic health registries. The study commenced with paediatric COVID-19 vaccination campaign at each site between June 2021 and January 2022. The outcome was hospitalisation with a laboratory-confirmed SARS-CoV-2 infection or COVID-19 as the main diagnosis. Using Cox proportional hazard models, VE was estimated as 1 minus the confounder-adjusted hazard ratio of COVID-19 hospitalisation between vaccinated and unvaccinated. A random-effects meta-analysis was used to pool VE estimates. Results: We included 4,144,667 5-11-year-olds and 3,861,841 12-17-year-olds. In 12-17-year-olds without previous infection, overall VE was 69% (95% CI: 40 to 84). VE declined with time since vaccination from 77% ≤ 3 months to 48% 180-365 days after immunisation. VE was 94% (95% CI: 90 to 96), 56% (95% CI: 3 to 80) and 41% (95% CI: -14 to 69) in the Delta, Omicron BA.1/BA.2 and BA.4/BA.5 periods, respectively. In 12-17-year-olds with previous infection, one dose VE was 80% (95% CI: 18 to 95). VE estimates were similar for 5-11-year-olds but with lower precision. Conclusion: Vaccines recommended for 5-17-year-olds provided protection against COVID-19 hospitalisation, regardless of a previously documented infection of SARS-CoV-2, with high levels of protection in the first 3 months of the vaccination.
- Cumulus cell DNA damage linked to fertilization success in females with an ovulatory dysfunction phenotypePublication . Rodrigues, Bárbara; Sousa, Vanessa; Esteves, Filipa; Vale-Fernandes, Emídio; Costa, Solange; Sousa, Daniela; Brandão, Raquel; Leal, Carla; Pires, Joana; Gaivão, Isabel; Teixeira, João Paulo; Nogueira, António J.A.; Jorge, PaulaIntracytoplasmic sperm injection (ICSI) is a widely used technique in fertility centers. ICSI success depends on both nuclear and cytoplasmic oocyte maturation. Cumulus cells, which surround the oocytes, play a pivotal role in oocyte competence. However, the significance of DNA damage in cumulus cells as a marker of fertilization success remains largely unexplored. This study aims to investigate the relationship between DNA damage in cumulus cells of females undergoing ICSI, and oocyte competence, with a focus on in vitro fertilization (IVF) outcomes. We employed the alkaline comet assay to assess DNA damage levels (%TDNA) in cumulus cells and whole blood from 22 potentially fertile females and 35 infertile females, including 20 with an ovulatory disfunction phenotype. Our results revealed significant differences between the levels of %TDNA in cumulus cells and blood. Females with an ovulatory dysfunction phenotype exhibited higher levels of %TDNA in cumulus cells compared to potentially fertile females. Additionally, within the group of females with ovulatory dysfunction, a significant correlation was observed between %TDNA levels and the number of oocytes with two pronuclei. Our findings suggest that blood does not accurately reflect DNA damage in cumulus cells, which was correlated with the fertilization success in females with ovulatory dysfunction. High levels of %TDNA in cumulus cells were associated with a higher likelihood of successful fertilization. Moreover, our results imply that low levels of %TDNA may be linked to oocytes that fail to complete maturation and, consequently, do not fertilize (oocytes with zero pronuclei). Further research with larger cohorts is necessary to validate these findings and to explore potential applications in female fertility. However, our study provides evidence that DNA damage in cumulus cells may serve as a valuable biomarker for predicting fertilization success and oocyte competence.
- Democratising participatory health promotion: power and knowledge involved in engaging European adolescents in childhood obesity preventionPublication . Baillergeau, Evelyne; Veltkamp, Gerlieke; Bröer, Christian; Helleve, Arnfinn; Kulis, Ewa; Lien, Nanna; Luszczynska, Aleksandra; Mendes, Sofia; Rito, Ana; Moerman, Gerben; Sauvage Nolting, Rein de; Klepp, Knut-IngePublic policy aimed at preventing undesired phenomena has increasingly sought to engage representatives of the target population. Little is known, however, about how power dynamics function to shape the processes and outcomes of risk governance engagement interventions. In order to study the ways in which, and the extent to which, power differentials can be reduced in participatory health promotion initiatives, we develop a conceptual framework synthetising theories of participatory action, phenomenology and governmentality. Based on the empirical research into youth participation in the EU project CO-CREATE, involving 15–19-year-old adolescents in five European countries (2019–2021), we show that diverse forms of knowledge may become available in engagement interventions. We analyse the use and relative inclusion and exclusion of these different forms of knowledge in terms of a three-level framework of different depths of democratisation in participatory health promotion: risk management, risk definition and risk negotiation. Advanced democratisation can only be achieved if risk negotiation is carried out in ways which embrace and encourage a range of different, and potentially conflicting forms of knowing.
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