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- The 24-Hour Activity Checklist for Cerebral Palsy: Translation, Content Validity and Test-Retest Reliability of Portuguese VersionsPublication . Vila-Nova, Fabio; Sá, Cristina; Leite, Hércules Ribeiro; Cadete, Ana; Folha, Teresa; Longo, Egmar; Martins, Maria Elisabete; Oliveira, RaulBackground: The importance of 24-h movement behaviour, including sleep, physical activity (PA) and sedentary behaviour (SB), has gained prominence due to its significant impact on the health and development of children, including those with cerebral palsy (CP). The 24-h activity checklist for CP, a tool developed in the Netherlands to monitor the activity in CP paediatric population, requires translation and cultural adaptation to Portuguese for use in Brazil and Portugal. Methods: This cross-sectional methodological study involved translating and culturally adapting the 24-h activity checklist for CP into Brazilian Portuguese (BP) and European Portuguese (EP) languages. The process included forward translation, synthesis and backward translation, expert panel evaluation and pretesting. Brazilian and Portuguese experts appraised content validity, assessed by the individual item (I-CVI) and scale level content validity index scores (S-CVI/Ave). Sixty parents of children with CP participated in the test-retest analysis, reported with the Intraclass Correlation Coefficients (ICCs). Results: I-CVI scores were higher than 0.78 for both versions. S-CVI/Ave scores were considered excellent for BP (0.91) and EP version (1.0). Expert's appraisal results in the inclusion of a question about sleep-related time indicators and the split of sleep, PA, and screen time questions for weekdays and weekends. Brazilian and Portuguese parents of children with CP reported understanding on instructions, questions, and answer options. The ICC values range from 0.81 to 0.99 and 0.6 to 0.98, for BP and EP, respectively. Conclusions: The BP and EP versions of 24-h activity checklist for CP demonstrated good content validity and test-retest reliability, supporting its use in Brazil and Portugal. This tool can contribute to improving communication between families and healthcare professionals to monitor and develop tailored interventions for healthy movement behaviours in children with CP.
- 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.
- Assessing the role of children in the COVID-19 pandemic in Belgium using perturbation analysisPublication . Angeli, Leonardo; Caetano, Constantino Pereira; Franco, Nicolas; Coletti, Pietro; Faes, Christel; Molenberghs, Geert; Beutels, Philippe; Abrams, Steven; Willem, Lander; Hens, NielUnderstanding the evolving role of different age groups in virus transmission is essential for effective pandemic management. We investigated SARS-CoV-2 transmission in Belgium from November 2020 to February 2022, focusing on age-specific patterns. Using a next generation matrix approach integrating social contact data and simulating population susceptibility evolution, we performed a longitudinal perturbation analysis of the effective reproduction number to unravel age-specific transmission dynamics. From November to December 2020, adults in the [18, 60) age group were the main transmission drivers, while children contributed marginally. This pattern shifted between January and March 2021, when in-person education resumed, and the Alpha variant emerged: children aged under 12 years old were crucial in transmission. Stringent social distancing measures in March 2021 helped diminish the noticeable contribution of the [18, 30) age group. By June 2021, as the Delta variant became the predominant strain, adults aged [18, 40) years emerged as main contributors to transmission, with a resurgence in children’s contribution during September-October 2021. This study highlights the effectiveness of our methodology in identifying age-specific transmission patterns.
- 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.
- Ciguatera toxins, a potential health risk emerging in Europe: overview of progress and challengesPublication . Alvito, Paula; Gago-Martínez, Ana; AlvitoCiguatera Poisoning (CP) is considered an emerging risk of concern in several places worldwide. The risk of CP in Europe is currently being investigated, and important advantages have been achieved under two EuroCigua projects, which allowed the characterization of Caribbean Ciguatoxins as the main responsible for the contamination in the European Coastal areas investigated. Important challenges and limitations, particularly the ones related to the lack of reference materials and of relevant samples that enable to associate the contaminated fish consumption with human intoxication, are the most critical aspects hindering the progress from both analytical and toxicological perspectives. This review aims to provide an update on the most recent advances in CP in Europe on the source of the toxins involved in contamination, their toxicology and pharmacology, and their detection and characterization in order to contribute to envisioning the toxic mechanism of CP in humans.
