RESUMO
Environmental exposures and gene-exposure interactions are the major causes of some diseases. Early-life exposome studies are needed to elucidate the role of environmental exposures and their complex interactions with biological mechanisms involved in childhood health. This study aimed to determine the contribution of early-life exposome to DNA damage and the modifying effect of genetic polymorphisms involved in air pollutants metabolism, antioxidant defense, and DNA repair. We conducted a cohort study in 416 Colombian children under five years. Blood samples at baseline were collected to measure DNA damage by the Comet assay and to determine GSTT1, GSTM1, CYP1A1, H2AX, OGG1, and SOD2 genetic polymorphisms. The exposome was estimated using geographic information systems, remote sensing, LUR models, and questionnaires. The association exposome-DNA damage was estimated using the Elastic Net linear regression with log link. Our results suggest that exposure to PM2.5 one year before the blood draw (BBD) (0.83, 95 %CI: 0.76; 0.91), soft drinks consumption (0.94, 0.89; 0.98), and GSTM1 null genotype (0.05, 0.01; 0.36) diminished the DNA damage, whereas exposure to PM2.5 one-week BBD (1.18, 1.06; 1.32), NO2 lag-5 days BBD (1.27, 1.18; 1.36), in-house cockroaches (1.10, 1.00; 1.21) at the recruitment, crowding at home (1.34, 1.08; 1.67) at the recruitment, cereal consumption (1.11, 1.04; 1.19) and H2AX (AG/GG vs. AA) (1.44, 1.11; 1.88) increased the DNA damage. The interactions between H2AX (AG/GG vs. AA) genotypes with crowding and PM2.5 one week BBD, GSTM1 (null vs. present) with humidity at the first year of life, and OGG1 (SC/CC vs. SS) with walkability at the first year of life were significant. The early-life exposome contributes to elucidating the effect of environmental exposures on DNA damage in Colombian children under five years old. The exposome-DNA damage effect appears to be modulated by genetic variants in DNA repair and antioxidant defense enzymes.
Assuntos
Poluentes Atmosféricos , Dano ao DNA , Exposição Ambiental , Interação Gene-Ambiente , Humanos , Pré-Escolar , Colômbia , Masculino , Feminino , Lactente , Expossoma , Estudos de Coortes , Glutationa Transferase/genética , Material Particulado , Polimorfismo Genético , Poluição do Ar/efeitos adversos , Poluição do Ar/estatística & dados numéricosRESUMO
Exposome studies are advancing in high-income countries to understand how multiple environmental exposures impact health. However, there is a significant research gap in low- and middle-income and tropical countries. We aimed to describe the spatiotemporal variation of the external exposome, its correlation structure between and within exposure groups, and its dimensionality. A one-year follow-up cohort study of 506 children under 5 in two cities in Colombia was conducted to evaluate asthma, acute respiratory infections, and DNA damage. We examined 48 environmental exposures during pregnancy and 168 during childhood in eight exposure groups, including atmospheric pollutants, natural spaces, meteorology, built environment, traffic, indoor exposure, and socioeconomic capital. The exposome was estimated using geographic information systems, remote sensing, spatiotemporal modeling, and questionnaires. The median age of children at study entry was 3.7 years (interquartile range: 2.9-4.3). Air pollution and natural spaces exposure decreased from pregnancy to childhood, while socioeconomic capital increased. The highest median correlations within exposure groups were observed in meteorology (r = 0.85), traffic (r = 0.83), and atmospheric pollutants (r = 0.64). Important correlations between variables from different exposure groups were found, such as atmospheric pollutants and meteorology (r = 0.76), natural spaces (r = -0.34), and the built environment (r = 0.53). Twenty principal components explained 70%, and 57 explained 95% of the total variance in the childhood exposome. Our findings show that there is an important spatiotemporal variation in the exposome of children under 5. This is the first characterization of the external exposome in urban areas of Latin America and highlights its complexity, but also the need to better characterize and understand the exposome in order to optimize its analysis and applications in local interventions aimed at improving the health conditions and well-being of the child population and contributing to environmental health decision-making.
Assuntos
Exposição Ambiental , Expossoma , Humanos , Colômbia/epidemiologia , Pré-Escolar , Feminino , Exposição Ambiental/análise , Masculino , Poluentes Atmosféricos/análise , Gravidez , Poluição do Ar/análise , Estudos de CoortesRESUMO
BACKGROUND: Exposure to air pollution during childhood has been linked with adverse effects on cognitive development and motor function. However, limited research has been done on the associations of air pollution exposure in different microenvironments such as home, school, or while commuting with these outcomes. OBJECTIVE: To analyze the association between childhood air pollution exposure in different microenvironments and cognitive and fine motor function from six European birth cohorts. METHODS: We included 1301 children from six European birth cohorts aged 6-11 years from the HELIX project. Average outdoor air pollutants concentrations (NO2, PM2.5) were estimated using land use regression models for different microenvironments (home, school, and commute), for 1-year before the outcome assessment. Attentional function, cognitive flexibility, non-verbal intelligence, and fine motor function were assessed using the Attention Network Test, Trail Making Test A and B, Raven Colored Progressive Matrices test, and the Finger Tapping test, respectively. Adjusted linear regressions models were run to determine the association between each air pollutant from each microenvironment on each outcome. RESULTS: In pooled analysis we observed high correlation (rs = 0.9) between air pollution exposures levels at home and school. However, the cohort-by-cohort analysis revealed correlations ranging from low to moderate. Air pollution exposure levels while commuting were higher than at home or school. Exposure to air pollution in the different microenvironments was not associated with working memory, attentional function, non-verbal intelligence, and fine motor function. Results remained consistently null in random-effects meta-analysis. CONCLUSIONS: No association was observed between outdoor air pollution exposure in different microenvironments (home, school, commute) and cognitive and fine motor function in children from six European birth cohorts. Future research should include a more detailed exposure assessment, considering personal measurements and time spent in different microenvironments.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Criança , Humanos , Poluentes Atmosféricos/toxicidade , Poluição do Ar/análise , Cognição , Estudos de Coortes , Exposição Ambiental/análise , Material Particulado/análise , Meios de TransporteRESUMO
Resumen Objetivo: Comparar características poblacionales y hallazgos placentarios asociados a óbito, en mujeres con infección asintomática por coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) al momento de la resolución del embarazo. Material y métodos: Estudio transversal analítico, mujeres con diagnóstico de óbito e infección asintomática por SARS-CoV-2. Se excluyeron pacientes con patología ginecológica y aquellas con más de una prueba RT-PCR. Resultados: No hay diferencia estadísticamente significativa entre las pacientes con infección asintomática por SARS-CoV-2 comparadas con pacientes sin infección para las características poblacionales como edad materna, antecedentes obstétricos, edad gestacional, escolaridad, estado civil, hábito tabáquico y enfermedades crónico-degenerativas. Tampoco hubo diferencia en los hallazgos placentarios de corioamnionitis, vasculitis, deciduitis, trombosis, aterosis aguda y necrosis fibrinoide. Conclusiones: No hay diferencia estadísticamente significativa en las características poblacionales y placentarias en embarazadas con diagnóstico de óbito, con y sin infección asintomática por SARS-CoV-2. Tenemos datos insuficientes para afirmar alguna característica asociada a óbito en pacientes con infección por SARS-CoV-2 asintomática.
Abstract Objective: To compare population characteristics and placental findings associated with stillbirth, in women with asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at the time of delivery. Materials and methods: Analytical cross-sectional study women with a diagnosis of stillbirth and with asymptomatic SARS-CoV-2 infection. Patients with gynecological pathology and those with more than one RT-PCR test were excluded. Results: There is no statistically significant difference between patients with asymptomatic SARS-CoV-2 infection compared to patients without infection for population characteristics such as maternal age, obstetric history, gestational age, education, marital status, smoking habit, chronic-degenerative diseases. There was no difference in placental findings of chorioamnionitis, vasculitis, deciduitis, thrombosis, acute atherosis, and fibrinoid necrosis. Conclusions: There is no statistically significant difference in the population and placental characteristics, in pregnant women diagnosed with stillbirth with and without confirmed asymptomatic SARS-CoV-2 infection. For the moment, we have insufficient data to affirm any population characteristic associated with stillbirth in patients with asymptomatic SARS-CoV-2 infection.
RESUMO
One recognized cause of cardiorespiratory diseases is air pollution. Older adults (OA) are one of the most vulnerable groups that suffer from its adverse effects. The objective of the study was to analyze the association between exposure to air pollution and changes in cardiorespiratory variables in OA. Observational prospective cohort study. Health questionnaires, blood pressure (BP) measurements, lung functions, respiratory symptoms, physical activity levels, and physical fitness in high and low exposure to air pollution were all methods used in evaluating OAs in communes with high contamination rates. Linear and logistic models were created to adjust for variables of interest. A total of 92 OA participated in this study. 73.9% of the subjects were women with 72.3 ± 5.6 years. 46.7% were obese, while 12.1% consumed tobacco. The most prevalent diseases found were hypertension, diabetes, and cardiovascular disease. Adjusted linear models maintained an increase for systolic BP of 6.77 mmHg (95% CI: 1.04-12.51), and diastolic of 3.51 mmHg (95% CI: 0.72-6.29), during the period of high exposure to air pollution. The adjusted logistic regression model indicated that, during the period of high exposure to air pollution increase the respiratory symptoms 4 times more (OR: 4.43, 95% CI: 2.07-10.04) in the OA. The results are consistent with an adverse effect on cardiorespiratory variables in periods of high exposure to air pollution in the OA population.
RESUMO
A new heterobifunctional linker containing an aldehyde-reactive aminooxy group and a thiol-reactive maleimide group, namely N-[4-(aminooxy)butyl]maleimide, was synthesized as a stable HCl salt by O-alkylation of either N-hydroxyphthalimide or N-(4-monomethoxytrityl)hydroxylamine, followed by N-alkylation of maleimide, in an overall yield of 18% (seven steps) or 29% (five steps), respectively. This heterobifunctional linker allowed a simple and efficient synthesis of a maleimide-containing thiol-reactive (18)F-labeling agent. Thus, N-[4-[(4-[(18)F]fluorobenzylidene)aminooxy]butyl]maleimide (specific activity: approximately 3000 Ci/mmol at end of synthesis) was synthesized in two steps involving the preparation of 4-[(18)F]fluorobenzaldehyde, followed by its aminooxy-aldehyde coupling reaction to the heterobifunctional linker, with an overall radiochemical yield of approximately 35% (decay corrected) within approximately 60 min from end of bombardment. Initial (18)F-labeling experiments were carried out using a thiol-containing tripeptide glutathione (GSH) and a 5'-thiol-functionalized oligodeoxynucleotide (5'-S-ODN) in phosphate-buffered saline (PBS, pH 7.5). After standing at room temperature for 10 min, the (18)F-labeled GSH and 5'-S-ODN were obtained in (18)F-labeling yields of approximately 70% and approximately 5% (decay-corrected), respectively. The heterobifunctional linker is easy to synthesize and provides a facile access to the maleimide-containing thiol-reactive (18)F-labeling agent, which could be advantageously employed in the development of (18)F-labeled biomomolecules for use with positron emission tomography.