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- Association between exposure to airborne endocrine disrupting chemicals and asthma in children or adolescents: A systematic review and meta-analysisPublication . Hatem, Georges; Faria, Ana Margarida; Pinto, Mariana Bessa; Teixeira, João Paulo; Salamova, Amina; Costa, Carla; Madureira, JoanaVarious studies have explored the association between Endocrine Disrupting Chemicals (EDCs) exposure and children's and adolescents' respiratory health, showing potential long-term effects and links to asthma. This systematic review explores the association between exposure to seven EDC groups during school age and adolescence and asthma onset or exacerbation while highlighting the predominant compounds underlying these potential associations. PubMed, Web of Science, Scopus, and Cochrane Library databases were searched with no time restriction. The risk of bias and heterogeneity across the included studies were assessed using the Newcastle Ottawa scale and I2 test, respectively. Pooled Odds Ratios (OR) and their 95% Confidence Intervals (CI) were calculated using the random effect model, and the quality of evidence for each outcome was measured using the GRADE approach. The review included 64851 children and adolescents from 61 observational studies, most with a low risk of bias in the studied domains. The pooled OR for asthma onset was significant for phthalates in dust samples (OR:1.21, CI:1.02; 1.44). Due to limited studies, the overall pooled effects for the other groups were not computed. Individual compounds demonstrating significant associations with asthma onset included airborne nickel (OR:1.10, CI:1.03; 1.18) and zinc (OR:1.13, CI:1.11; 1.15), urinary Bisphenol S (OR:1.40, CI:1.13; 1.73), Bisphenol A (OR:1.57, CI:1.02; 2.40) and arsenic (OR:2.08, CI:1.33; 3.26), and DiBP (OR:1.41, CI:1.08; 1.82), DEHP (OR:1.89, CI:1.00; 3.57), and TBOEP (OR:2.61, CI:1.08; 6.30) in the dust. Individual compounds with significant associations with greater asthma exacerbation odds comprised airborne nickel (OR:1.08, CI:1.01; 1.16) and zinc (OR:1.09, CI:1.01; 1.17), and urinary MEHHP (OR:1.24, CI:1.02; 1.51), MECPP (OR:1.30, CI:1.07; 1.57), MEOHP (OR:1.30, CI:1.09; 1.55), and MCOP (OR:1.32, CI:1.11; 1.57). Exposure to EDCs was significantly associated with asthma onset and exacerbation in children and adolescents, namely for phthalates, bisphenols A and S, arsenic, nickel, and zinc. Further research is recommended to focus on the impact of synergistic and co-exposure to other indoor air pollutants.
- Exposure to per-and poly-fluoroalkyl substances and respiratory and skin effects in children and adolescents: A systematic review and meta-analysisPublication . Hatem, Georges; Faria, Ana Margarida; Pinto, Mariana Bessa; Salamova, Amina; Teixeira, João Paulo; Costa, Carla; Madureira, JoanaDespite being previously banned due to long-term health effects, Per- and polyfluoroalkyl substances (PFAS) remain widespread in the environment, accumulating in animals and humans. This systematic review and meta-analysis explores associations between exposure to PFAS and asthma onset, wheezing, atopic dermatitis, and eczema in children and adolescents while addressing exposure timing and sex-specific differences. After comprehensive search conducted in several databases, including risk of bias, study heterogeneity, and quality of evidence evaluation, the review included 28 observational studies, most with low risk of bias in all domains. PFAS exposure was not significantly associated with asthma onset (OR:1.03, CI:0.99;1.07), but revealed significantly lower association in the prenatal period (OR:0.97, CI:0.94;0.99), higher in the postnatal period (OR:1.20, CI:1.07;1.35), and no differences among sexes. PFAS exposure (mainly prenatal) was associated with 4 % significantly lower odds of wheezing (OR:0.96, CI:0.94;0.98), higher in girls (OR:0.94, CI:0.91;0.98) than in boys (OR:0.97, CI:0.94;1.00). No significant impact was noted on atopic dermatitis (OR:1.04, CI:0.94;1.16), while PFAS exposure was associated with 8 % significantly lower eczema odds (OR:0.92, CI:0.89;0.96). Evidence was insufficient to perform sensitivity analyses on atopic dermatitis and eczema. Additional research is needed on the impact of synergistic and co-exposure to other pollutants on children and adolescents' health.
- Biocompatibility testing and antioxidant properties of cerium dioxide nanoparticles in human nervous system cellsPublication . Fernández-Bertólez, Natalia; Touzani, Assia; Ramos-Pan, Lucía; Reis, Ana Teresa; Teixeira, João Paulo; Laffon, Blanca; Valdiglesias, VanessaCerium dioxide nanoparticles (CeO NP), or nanoceria, are versatile materials with interesting properties for industry and medicine fields, particularly redox properties and catalytic activity. Because of their distinctive features, they have gained high attention in biomedical and pharmacological research to be employed in drug delivery, tissue regeneration, radioprotection, or diagnostic imaging. However, previous works reported that nanoceria may also induce reactive oxygen species (ROS) under certain conditions, leading to cellular stress, cellular damage, or cell death. In this study, the effects of CeO NP on cell viability and morphology as well as their influence on oxidative stress (both oxidant and ROS scavenging capacities) were investigated in nervous system cells (SH-SY5Y neuronal and A172 glial cells) treated with a wide range of CeO NP concentrations (1-100 µg/mL) for several treatment times. Results obtained showed that, despite being stable in time and effectively internalized by both cell types, CeO NP did not produce significant decrease in viability, evaluated by MTT assay, morphological alterations, or intrinsic cell-free ROS, but they generated cellular ROS limited to longer exposure periods. Furthermore, CeO NP demonstrated a certain intrinsic ability to scavenge ROS generated by HO in both tested cell types, more pronounced in neuronal cells. These results confirm the good biocompatibility of nanoceria on human nervous system cells and support further exploring their potential use in biomedicine field, particularly for those therapeutic and diagnostic applications related to the nervous system.
- Lifestyle, environment and other major determinants of frailty in older adults: a population-based study from the UK BiobankPublication . Hemadeh, Ali; Lema-Arranz, Carlota; Bonassi, Stefano; Buscarini, Leonardo; Infarinato, Francesco; Romano, Paola; Finti, Alessia; Marinozzi, Franco; Bini, Fabiano; Fernández-Bertólez, Natalia; Teixeira, João Paulo; Lorenzo-López, Laura; Valdiglesias, Vanessa; Laffon, BlancaFrailty is a geriatric multidimensional syndrome characterized by a loss of physiologic reserves and disproportionate vulnerability to external stressors and associated with increased risk of multiple negative health outcomes. Since frailty can be prevented, controlled, and even reverted in its early stages, identifying the main factors involved in its development is crucial to implement preventive and/or restorative interventions. The aim of this study was to assess the impact of a broad range of parameters, including host factors, lifestyle, diet, and environmental and occupational conditions, on the development of frailty in later life. A cross-sectional study was conducted on 221,896 individuals aged 60 and over classified as non-frail (119,332, 53.8%), pre-frail (93,180, 42.0%), and frail (9384, 4.2%) according to the frailty phenotype. Using principal component analysis and machine learning to streamline the data, significant associations were found between frailty risk and air quality, diet, smoking, working conditions, and heavy alcohol consumption. Early-life factors, including breastfed as a baby and maternal smoking around birth, also emerged as predictors of frailty, which was further characterized by clinical indicators like polypharmacy, levels of C-reactive protein and other biomarkers of inflammageing. This study provided robust and original evidence on the association between a large battery of potential risk factors, from early to later stages of life, and the occurrence of frailty in older age. These results will contribute to the development of effective prevention strategies and facilitate the early detection of individuals at high risk of developing frailty.
- Impact of occupational exposure to wildfire events on systemic inflammatory biomarkers in Portuguese wildland firefightersPublication . Esteves, Filipa; Madureira, Joana; Barros, Bela; Alves, Sara; Pires, Joana; Martins, Sandra; Oliveira, Marta; Vaz, Josiana; Slezakova, Klara; Pereira, Maria do Carmo; Fernandes, Adília; Morais, Simone; Guimarães, João Tiago; Bonassi, Stefano; Teixeira, João Paulo; Costa, SolangeWhile occupational exposure as a firefighter is considered a dangerous occupation, research on the underlying mechanisms remains limited, particularly in wildland firefighters. Inflammation, a key effect of wildfire exposure, plays a significant role in the development of various diseases. The current study aims to investigate the impact of wildland firefighting exposure on the levels of pro-inflammatory systemic biomarkers. A pre-post study design investigated 59 wildland firefighters comparing data collected after participation in a wildfire event (Phase II) with data obtained before wildfire season (Phase I). Data on demographics, lifestyle, health and occupational-related factors were assessed. Exposure factors, such as fire combat (e.g., exposure duration), were also registered. Inflammatory biomarkers (i.e. interleukin-6 [IL-6], interleukin-8 [IL-8], tumor necrosis factor α [TNF-α] and high-sensitivity C-reactive protein [hs-CRP]) and hydroxylated polycyclic aromatic hydrocarbons metabolites (1-OHNaph+1-OHAce, 2-OHFlu, 1-OHPhen, 1-OHPyr) were analysed in blood and urine samples, respectively. Serum IL-8 and IL-6 levels were significantly increased after wildland fire combat. IL-8 levels were 2.62 times higher (95 % CI: 1.96-3.50; p < 0.01), whereas IL-6 levels were 1.25 times higher (95 % CI: 1.00-1.57; p = 0.04). Furthermore, IL-8 levels were significantly correlated with urinary 2-hydroxyfluorene levels and fire combat duration (>12 h). In addition, the mean hs-CRP level, in both phases, was above 3.0 mg/L, indicating a potential risk for cardiovascular events. Given the long-term health implications of firefighting occupational exposure, biomonitoring and early detection of occupational risks are essential for protecting firefighters' health. Protective measures must be urgently implemented to enhance occupational health and strengthen preventive strategies in this sector.
- Occupational exposure to wildland firefighting and its effects on systemic DNA damagePublication . Esteves, Filipa; Madureira, Joana; Costa, Carla; Pires, Joana; Barros, Bela; Alves, Sara; Vaz, Josiana; Oliveira, Marta; Slezakova, Klara; Fernandes, Adília; Pereira, Maria do Carmo; Morais, Simone; Valdiglesias, Vanessa; Bonassi, Stefano; Teixeira, João Paulo; Costa, SolangeBackground: Portugal is among the European Union countries more devastated by forest fires. Wildland firefighters are at the forefront of this battle, facing exposure to a wide range of harmful pollutants. Epidemiological studies have highlighted a potential link between occupational firefighting exposure and several diseases, including cancer. To date, very few studies have explored the biological mechanisms associated with such exposure. The present longitudinal study aims to assess changes in early effect biomarkers following wildland firefighters' occupational exposure to a real wildfire event. Methods: Paired blood samples from 59 healthy Portuguese wildland firefighters were collected at two different time points: before wildfire season and after a fire event during wildfire season. Sociodemographic variables (e.g., age, sex) and work-related factors (e.g., years of service) were assessed via a self-reported questionnaire. Levels of early effect biomarkers, such as primary DNA damage and oxidative DNA damage (oxidised purines) were assessed via comet assay. DNA double-strand breaks (DSBs) were evaluated by phosphorylated H2AX (γH2AX). Moreover, hydroxylated polycyclic aromatic hydrocarbon metabolites (OHPAHs) and metal(loid)s were quantified in urine samples. The influence of urinary OHPAHs, urinary metal(loid)s, and other exposure-related factors (e.g., firefighting duration) on changes (Δ) in early effect biomarkers (post-vs. baseline levels) was investigated. Results: Firefighting activities led to a significant increase in both primary DNA damage and oxidative DNA damage by 22 % (95 % CI: 1.11-1.35; p < 0.05) and 23 % (95 % CI: 1.04-1.45; p < 0.05), respectively. Results from linear regression revealed that per each unit increase of urinary 2-hydroxyfluorene (2-OHFlu) (μmol/mol creatinine), the risk of ⧍ oxidative DNA damage increased by 20 % [FR: 1.20 (1.09-1.32); p < 0.01]. Additionally, each unit increase in urinary cesium (Cs) (μg/L) resulted in a significant 4 % increase in Δ primary DNA damage [FR: 1.04 (1.01-1.06); p < 0.05] and a 3 % increase in Δ oxidative DNA damage [FR: 1.03 (1.01-1.05); p < 0.05]. Post-exposure levels of γH2AX were significantly correlated with urinary 2-OHFlu levels assessed after firefighting (r = 0.30; p < 0.05). Furthermore, exposure duration and reported breathing difficulties during firefighting were significantly associated with increased levels of primary DNA damage. Conclusion: Results obtained provide insights into the potential human health effects of wildland firefighting occupational exposure at the genetic and molecular levels, offering new and important mechanistic data. These findings are crucial for implementing health and safety measures, recommendations, and best practices to mitigate occupational risks and protect the health of wildland firefighters.
- Comparative efficacy of essential oils against Cutibacterium acnes: Effect upon strains from phylotypes with different virulence patternsPublication . Oliveira, Ana Sofia; Gaspar, Carlos; Rolo, Joana; Palmeira-de-Oliveira, Rita; Teixeira, João Paulo; Martinez-de-Oliveira, José; Palmeira-de-Oliveira, AnaObjectives: Despite being a commensal of human skin, Cutibacterium acnes plays an important role in the pathogenesis of Acne vulgaris, with the loss of bacterial phylotype diversity being related to disease progression. This study evaluated differences in the virulence profile of C. acnes strains from different phylotypes and investigated the possible phylotype-selective efficacy of essential oils (EOs) from Thymus x citriodorus (TC), Thymus mastichina, and Cistus ladanifer compared to Melaleuca alternifolia (tea tree), focusing on both planktonic and biofilm growth forms, the latter being related with pathogenesis and treatment resistance. Methods: One collection strain and seven clinical isolates were classified into phylotypes using multiplex-touchdown PCR. Virulence trait differences across phylotypes were evaluated by studying antibiotic resistance, biofilm formation, porphyrin production, and lipase activity. EOs were tested for minimum inhibitory/bactericidal concentrations (MIC/MBC) and effects on biofilm biomass and metabolic activity. Results: Strains from phylotype IA1 were higher biofilm and lipase producers than phylotype II strains. Regarding EO's efficacy, TC EO presented lower planktonic MIC values for all strains compared to the other EOs, presenting a smaller difference in MIC values across phylotypes. TC EO was able to similarly reduce biofilm biomass and metabolic activity in phylotype IA1 clinical strains, being effective at lower concentrations compared with the remaining EOs. Conclusions: Not all virulence traits were phylotype-related, highlighting the multifactorial nature of the disease. TC EO showed a relevant anti-acne potential, outperforming tea tree EO (a species with a commercial claim for Acne vulgaris) against both planktonic and biofilm growth forms of C. acnes.
- Genetic and Epigenetic Alterations Associated With Human Prenatal Tobacco and Environmental Tobacco Smoke Exposure: Protocol for a Systematic Evidence MapPublication . Reis, Ana Teresa; Madureira, Joana; Teixeira, João Paulo; Costa, CarlaObjectives: This protocol outlines the development of a systematic evidence map (SEM) on genetic and epigenetic alterations associated with human prenatal tobacco exposure. The SEM will identify and synthetize epidemiological data on periconceptional and prenatal tobacco exposure associated with genetic (e.g., DNA damage) and epigenetic (e.g., DNA methylation) outcomes. Furthermore, it will describe the available evidence, highlight knowledge clusters, and identify gaps for future research. Methods: Bibliographic databases and grey literature sources will be searched, complemented by reference mining. Predefined inclusion and exclusion criteria will guide study inclusion. Data extraction will include population, exposure, comparator, outcome, funding, study design, confounding factors, and statistical methods. Summarization will include a narrative review, graphical visualization, and an interactive, queryable and open-access table. Results: A pilot study assessed the protocol's feasibility, testing key components, including screening, data extraction, and eligibility criteria. Findings confirmed that the methodology is workable and reliable. Conclusion: This protocol supports a rigorous, reproducible, transparent SEM, aligned with international standards. The comprehensive mapping will support research prioritization and inform public health policies targeting maternal and child health.
- Impact of wildfire emissions exposure on the associations between levels of lung injury, lipid peroxidation, DNA oxidation, and exposure biomarkersPublication . Barros, Bela; Paiva, Ana Margarida; Azevedo, Rui; Alves, Sara; Esteves, Filipa; Fernandes, Adília; Vaz, Josiana; Alves, Maria José; Slezakova, Klara; Teixeira, João Paulo; Costa, Solange; Almeida, Agostinho; Oliveira, Marta; Morais, SimoneFirefighters face increased risks of developing cardio-respiratory diseases and cancer. This study aimed, for the first time, to simultaneously characterize several biomarkers of effect (lung injury by Clara cell 16 -CC16, lipid peroxidation by 8-isoprostane-8-iso, and DNA oxidation by 8-hydroxy-2-deoxyguanosine-8-OHdG) and exposure (polycyclic aromatic hydrocarbons metabolites - 6 OHPAHs and 17 metal(loid)s) in (pre- and post-exposure) paired urine samples of wildland firefighters, while exploring their inter-/intra-associations and accounting for tobacco consumption. Wildfire combat influenced the levels of CC16 (+39 %), 8-iso (+33 %), 8-OHdG (-13 to +19 %), individual and sum of OHPAHs (+75-211 %), and metal(loid)s (up to 43 %, p > 0.05: lithium, zinc, antimony, and lead); post-exposure increments were more evident among non-smokers. Post-exposure (individual and sum) OHPAHs and some metal(loid)s (copper, cadmium, barium, antimony, copper, lead, zinc, selenium, and rubidium) were positively associated with CC16, 8-iso and/or 8-OHdG (0.609 < r < 0.838; 0.001 < p < 0.047). Spearman's correlations and principal component analysis highlighted CC16 as the best discriminant effect biomarker of wildland firefighting, correlating positively with individual and sum of OHPAHs, cadmium, barium and copper (0.647 < r < 0.764; 0.006 < p < 0.031). Cumulative exposure to wildfires and tobacco contributed to positive correlations (0.587 < r < 0.715; 0.009 < p < 0.045) between lipid peroxidation and arsenic, antimony, lead, and copper, and between DNA oxidation and lead. Smoking firefighters presented higher OHPAHs baseline concentrations (2- to 14-fold), and lung injury and DNA oxidation induced by cadmium, copper, strontium, cesium, barium and thallium (0.661 < r < 0.709; 0.022 < p < 0.038). Given firefighter's carcinogenic risks, performing similar studies in larger groups is crucial to enhance risk assessment by establishing a well-defined panel of effect and exposure biomarkers.
- An introduction to BASIC Guide: human biomonitoring and surveillance of chemical exposure in occupational settingsPublication . Zare Jeddi, Maryam; Jones, Kate; Leese, Elizabeth; Fustinoni, Silvia; Galea, Karen S.; Santonen, Tiina; Porras, Simo P.; Hopf, Nancy B.; Göen, Thomas; Bader, Michael; Tranfo, Giovanna; Tristram, Adrian; Iavicoli, Ivo; Leso, Veruscka; Koch, Holger M.; Pasanen-Kase, Robert; Boogaard, Peter J.; Persoons, Renaud; Esteban-López, Marta; Verpaele, Steven; Kasiotis, Konstantinos M.; Machera, Kyriaki; Carrieri, Mariella; Palmen, Nicole; Duca, Radu-Corneliu; van Nieuwenhuyse, An; Gonzales, Melissa; Haynes, Erin N.; Viegas, Susana; Bessems, Jos; Makris, Konstantinos C.; Connolly, Alison; Teixeira, João Paulo; Chung, Ming Kei; Parsons, Patrick J.; Kumar, Eva; Lin, Elizabeth Ziying; Kil, Jihyon; Kwon, Jung-Hwan; Tavares, Ana Maria; Vekic, Ana Maria; Souza, Gustavo; Scheepers, Paul T. J.Human biomonitoring (HBM) complements air and surface measurements by integrating exposure from all routes and sources, strengthening occupational exposure assessment and control. In occupational settings, HBM can quantify exposure during routine work and nonroutine activities, evaluate controls, investigate incidents (potential overexposures), and support medical surveillance. To use HBM to its full potential, occupational health and safety professionals (OHPs) should adopt harmonized biomonitoring approaches reflecting best practice. This short communication presents the BASIC Guide series (Human Biomonitoring and Surveillance of Chemical Exposure in Occupational Settings), initiated by the International Society of Exposure Science Human Biomonitoring working group (ISES Europe HBM WG) as an integral part of the HBM Global Network. These chemical-specific practical documents operationalize the OECD (Organisation for Economic Co-operation and Development) occupational biomonitoring guidance, supporting the consistent implementation of exposure biomonitoring programs. Each BASIC Guide provides clear instructions on biomarker selection, sample handling, analytical methods, quality assurance, and result interpretation and communication. By translating international frameworks into actionable protocols, the BASIC Guides improve reproducibility and regulatory alignment in occupational HBM and enable more defensible exposure assessments worldwide.