Prenatal and early life exposure to fine particulate matter and telomere length in early childhood.

BACKGROUND: Telomere length is a biomarker of molecular aging that may be impacted by air pollution exposure starting in utero. We aimed to examine the association between prenatal and early life exposure to fine particulate matter (PM2.5) and leukocyte telomere length (LTL) in children and explore sex differences. METHODS: Analyses included 384 mother-child pairs enrolled in the Programming Research in Obesity, Growth, and Environmental Stressors (PROGRESS) birth cohort in Mexico City. Exposure to PM2.5 was estimated at the residential level using a satellite based spatio-temporally resolved prediction model. Average relative LTL was measured in DNA isolated from blood collected at age 4-6 years using quantitative real-time polymerase chain reaction. Linear regression models were used to examine the association between average PM2.5 across pregnancy, individual trimesters, first postnatal year, and LTL. Models were adjusted for maternal age and education at enrollment, prenatal environmental tobacco smoke exposure, child sex, age, and body mass index z-score at LTL measurement. Effect modification by sex was investigated with interaction terms and stratification. RESULTS: In trimester specific models, we found an association between 2nd trimester PM2.5 and elongated LTL (ß: 4.34, 95%CI [0.42, 8.42], per 5 µg/m3 increase). There was suggestive effect modification by sex on average 2nd trimester PM2.5 with stronger associations seen in females compared to males (ß: 7.12, [95%CI: 0.98, 13.6] and ß: 1.43 [95%CI: -3.46, 6.57]) per 5 µg/m3 increase respectively. CONCLUSION: Second trimester PM2.5 levels were associated with changes in LTL in early childhood. Understanding temporal and sex differences in PM2.5 exposure may provide insights into telomere dynamics over early life.

Prenatal exposure to phthalates and childhood wheeze and asthma in the progress cohort.

INTRODUCTION: Prenatal phthalate exposure may influence lung development and lead to wheezing and asthma in childhood, and these associations may vary by sex. Despite ubiquity of exposure, there is limited epidemiologic data on these associations in Latin America. METHODS: We assessed 593 mother-child dyads enrolled in the Programming Research in Obesity, Growth, Environment, and Social Stressors birth cohort in Mexico City. We quantified 15 phthalate metabolites in 2nd and 3rd trimester maternal urine. Report of ever wheeze, wheeze in the past 12 months (current wheeze) and ever asthma were obtained using a validated survey when children were 4 and 6 years of age. We examined individual associations with modified Poisson models. Mixture effects were assessed using Bayesian Weighted Quantile Sum (BWQS) regression. All models were adjusted for child's sex, maternal age and education at enrollment, and parity. RESULTS: In Poisson models, a doubling of mono (carboxy-isononyl) phthalate (MCNP) during the 2nd trimester was associated with higher risk of wheeze (RR: 1.14, 95 % CI: 1.01, 1.29), and asthma (RR: 1.44, 95 % CI: 1.05, 1.97) at 4 years of age. Higher concentrations of the sum of di-isononyl phthalate metabolites (∑DiNP) during the 2nd trimester were also associated with asthma at 4 years of age (RR: 1.30, 95 % CI: 1.04, 1.61). Mixture associations of phthalate metabolite concentrations during the 2nd trimester and asthma at 4 years of age were stronger in males (BWQS, OR: 1.94, 95 % CI: 0.90, 4.60; 90 % CrI: 1.04, 3.73) compared to females (BWQS, OR: 1.23, 95 % CI: 0.56, 2.88; 90 % CrI: 0.61, 2.55). Additionally, we observed stronger inverse associations between prenatal phthalate mixtures during the 3rd trimester and current wheeze at 4 and 6 years of age in females (BWQS, OR: 0.54, 90 % CrI: 0.35, 0.82; OR: 0.45, 90 % CrI: 0.22, 0.84) compared to males (BWQS, OR: 0.95, 90 % Cri: 0.68, 1.35; OR: 0.97, 90 % CrI: 0.59, 1.54). CONCLUSIONS: Prenatal phthalate metabolite concentrations were associated with respiratory outcomes in childhood, with some evidence of sex specific effects. Future work investigating phthalate exposure and wheeze trajectories/lung function will be important for understanding how these may predict later disease.

The Impact of the Coronavirus Disease 2019 Pandemic on Helicopter Emergency Medical Services.

The coronavirus disease 2019 pandemic has profoundly affected the Lombardy healthcare system. Although air transport of critical patients played a crucial role, there are still gaps in understanding how the pandemic impacted helicopter emergency medical services (HEMS). A retrospective observational analysis was performed using data from the regional emergency-urgency online portal. The investigation focused on patients airlifted by helicopter to the Lombardy emergency departments from January 1, 2019, to December 31, 2021. A total of 12,953 admissions to the emergency departments have been recorded (5,733 in 2019, 3,550 in 2020, and 3,670 in 2021). The monthly average of events changed significantly over the 3 years (2019 [477.7], 2020 [295.8], and 2021 [305.8]) (P < .001). Additionally, there was a notable increase in the percentage of severe cases with red triage codes in 2020 (28.9%) and 2021 (33.5%) compared with 2019 (19.9%). Moreover, the number of hospitalized patients increased in 2020 (39.9%) and 2021 (37.2%) compared with 2019 (27.7%). The HEMS documented a noteworthy decrease in mission numbers and an increase in patient clinical severity during the pandemic. Consequently, the HEMS might be allocated for specific roles in national pandemic plans during the alert phase activation, such as secondary transport between hospital facilities.

Associations between psychosocial stress, child's anxiety, and lung function in mid-childhood.

BACKGROUND: Reducing the risk of respiratory disease during the plastic stages of lung development could have long-term health impacts. Psychosocial stress has been previously linked to adverse childhood respiratory outcomes, but the influence of child's anxiety and sex differences has not been completely elucidated. OBJECTIVE: To evaluate the association among maternal stress, child anxiety, and lung function in children and to explore differences by sex. METHODS: Cross-sectional analyses included 294 mother-child pairs from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) birth cohort in Mexico City. Children's lung function was tested once at ages 8 to 13 years of age, and height- and sex-adjusted z-scores were estimated for forced vital capacity, forced expiratory volume in 1 second, forced expiratory volume in 1 second/forced vital capacity and forced expiratory flow between 25% and 75%. Maternal stress was assessed through the Crisis in Family Systems-Revised (CRISYS-R) survey, used to report negative life events experienced in the past 6 months and dichotomized at the median (<3 and ≥3). Child's self-reported anxiety was assessed using the Revised Children's Manifest Anxiety Scale short form and dichotomized at the clinically relevant cutoff (T-score ≥ 60). The association among maternal stress, child anxiety, and lung function outcomes was evaluated using linear models. Effect modification by sex was evaluated with interaction terms and in stratified analyses. RESULTS: We did not find any association between maternal stress and any lung function outcome. Clinically elevated child anxiety symptoms were associated with lower forced expiratory volume in 1 second (ß = -0.36, 95% CI -0.69 to -0.02). We found no evidence of effect modification by sex. CONCLUSION: Results highlight the importance of considering childhood mental health in relation to lung function outcomes.

Association of pesticide exposure with respiratory health outcomes and rhinitis in avocado farmworkers from Michoacán, Mexico.

BACKGROUND: A growing literature suggests associations between occupational pesticide exposure and respiratory health. In this study, we aimed to examine the association of exposure to insecticides, fungicides, and herbicides, individually and as a mixture, with respiratory health outcomes and rhinitis in avocado farmworkers from Michoacán, Mexico. MATERIAL AND METHODS: We conducted a cross-sectional study of 105 avocado farmworkers between May and August 2021. We quantified 12 insecticide, fungicide, and herbicide metabolites in urine samples collected during two study visits (8-10 weeks apart). We collected survey data on self-reported pesticide use during the 12 months prior to the baseline survey and estimated annual exposure-intensity scores (EIS) using a semi-quantitative exposure algorithm. We also assessed respiratory symptoms, including wheezing, chest tightness, wheezing after exercise, and night cough. We used generalized linear regression models to examine associations of individual urinary metabolite concentrations and annual EIS with respiratory health outcomes and rhinitis. Mixture effects were assessed using Bayesian Weighted Quantile Sum (BWQS) regression. RESULTS: After adjusting for multiple comparisons, we observed mostly null associations of individual pesticide metabolite concentrations and annual EIS with the outcomes of interest. However, in BWQS analyses, we found evidence of a mixture association of urinary pesticide metabolites with increased odds of night cough (OR: 5.34, 95 % CrI: 1.67, 20.62). Pyrethroid metabolites 3-phenoxybenzoic acid and cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid were the main contributors to this association (43 %). CONCLUSIONS: Our findings indicate that exposure to a mixture of pesticides, particularly pyrethroid insecticides, may be associated with night cough in avocado farmworkers.

Associations of prenatal exposure to phthalates and their mixture with lung function in Mexican children.

Early life phthalates exposure has been associated with adverse respiratory outcomes. However, evidence linking prenatal phthalates exposure and childhood lung function has been inconclusive. Additionally, few studies have examined phthalates exposure as a mixture and explored sexually dimorphic associations. We aimed to investigate sex-specific associations of prenatal phthalates mixtures with childhood lung function using the PROGRESS cohort in Mexico (N = 476). Prenatal phthalate concentrations were measured in maternal urine collected during the 2nd and 3rd trimesters. Children's lung function was evaluated at ages 8-13 years. Individual associations were assessed using multivariable linear regression, and mixture associations were modeled using repeated holdout WQS regression and hierarchical BKMR; data was stratified by sex to explore sex-specific associations. We identified significant interactions between 2nd trimester phthalates mixture and sex on FEV1 and FVC z-scores. Higher 2nd trimester phthalate concentrations were associated with higher FEV1 (ß = 0.054, 95 %CI: 0.005, 0.104) and FVC z-scores (ß = 0.074, 95 % CI: 0.024, 0.124) in females and with lower measures in males (FEV1, ß = -0.017, 95 %CI: -0.066, 0.026; FVC, ß = -0.014, 95 %CI: -0.065, 0.030). This study indicates that prenatal exposure to phthalates is related to childhood lung function in a sex-specific manner.

Associations between prenatal metal and metalloid mixtures in teeth and reductions in childhood lung function.

BACKGROUND: Metal(oid)s have been cross-sectionally associated with lung function outcomes in childhood but there is limited data on their combined effects starting in utero. Child sex may further modify these effects. OBJECTIVE: Examine associations between in utero and early life exposure to metals assessed via novel dentine biomarkers and childhood lung function and explore effect modification by child sex. METHODS: Analyses included 291 children enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study, a longitudinal birth cohort study in Mexico City. Weekly dentine levels of arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), manganese (Mn), nickel (Ni), and lead (Pb) were measured from 15 weeks pre-birth to 15 weeks post birth in deciduous children's teeth. Lung function was tested at ages 8-14 years and then modeled as age, height and sex adjusted z-scores. Associations were modeled using lagged weighted quantile sum (LWQS) regression to evaluate the potential for a time-varying mixture effect adjusting for maternal age and education at enrollment and exposure to environmental tobacco smoke in pregnancy. Models were also stratified by sex. RESULTS: We identified a window of susceptibility at 12-15 weeks pre-birth in which the metal mixture was associated with lower FVC z-scores in children aged 8-14 years. Cd and Mn were the largest contributors to the mixture effect (70 %). There was also some evidence of effect modification by sex, in which the mean weights and weighted correlations over the identified window was more evident in males when compared to females. In the male stratum, Cd, Mn and additionally Pb also dominated the mixture association. CONCLUSIONS: Prenatal metal(oid) exposure was associated with lower lung function in childhood. These findings underscore the need to consider both mixtures and windows of susceptibility to fully elucidate effects of prenatal metal(oid) exposure on childhood lung function.

C. elegans: a prominent platform for modeling and drug screening in neurological disorders.

INTRODUCTION: Human neurodevelopmental and neurodegenerative diseases (NDevDs and NDegDs, respectively) encompass a broad spectrum of disorders affecting the nervous system with an increasing incidence. In this context, the nematode C. elegans, has emerged as a benchmark model for biological research, especially in the field of neuroscience. AREAS COVERED: The authors highlight the numerous advantages of this tiny worm as a model for exploring nervous system pathologies and as a platform for drug discovery. There is a particular focus given to describing the existing models of C. elegans for the study of NDevDs and NDegDs. Specifically, the authors underscore their strong applicability in preclinical drug development. Furthermore, they place particular emphasis on detailing the common techniques employed to explore the nervous system in both healthy and diseased states. EXPERT OPINION: Drug discovery constitutes a long and expensive process. The incorporation of invertebrate models, such as C. elegans, stands as an exemplary strategy for mitigating costs and expediting timelines. The utilization of C. elegans as a platform to replicate nervous system pathologies and conduct high-throughput automated assays in the initial phases of drug discovery is pivotal for rendering therapeutic options more attainable and cost-effective.

Association between prenatal and childhood PM2.5 exposure and preadolescent anxiety and depressive symptoms.

Background: Fine particulate matter (PM2.5) exposure has been linked to anxiety and depression in adults; however, there is limited research in the younger populations, in which symptoms often first arise. Methods: We examined the association between early-life PM2.5 exposure and symptoms of anxiety and depression in a cohort of 8-11-year-olds in Mexico City. Anxiety and depressive symptoms were assessed using the Spanish versions of the Revised Children's Manifest Anxiety Scale and Children's Depression Inventory. Daily PM2.5 was estimated using a satellite-based exposure model and averaged over several early and recent exposure windows. Linear and logistic regression models were used to estimate the change in symptoms with each 5-µg/m3 increase in PM2.5. Models were adjusted for child's age, child's sex, maternal age, maternal socioeconomic status, season of conception, and temperature. Results: Average anxiety and depressive symptom T-scores were 51.0 (range 33-73) and 53.4 (range 44-90), respectively. We observed consistent findings for exposures around the fourth year of life, as this was present for both continuous and dichotomized anxiety symptoms, in both independent exposure models and distributed lag modeling approaches. This window was also observed for elevated depressive symptoms. An additional consistent finding was for PM2.5 exposure during early pregnancy in relation to both clinically elevated anxiety and depressive symptoms, this was seen in both traditional and distributed lag modeling approaches. Conclusion: Both early life and recent PM2.5 exposure were associated with higher mental health symptoms in the child highlighting the role of PM2.5 in the etiology of these conditions.

The neurohormone tyramine stimulates the secretion of an Insulin-Like Peptide from the intestine to modulate the systemic stress response in C. elegans.

The DAF-2/insulin/insulin-like growth factor signaling (IIS) pathway plays an evolutionarily conserved role in regulating reproductive development, lifespan, and stress resistance. In C. elegans , DAF-2/IIS signaling is modulated by an extensive array of insulin-like peptides (ILPs) with diverse spatial and temporal expression patterns. However, the release dynamics and specific functions of these ILPs in adapting to different environmental conditions remain poorly understood. Here, we show that the ILP, INS-3, plays a crucial role in modulating the response to different types of stressors in C. elegans . ins-3 mutants display increased resistance to both heat and oxidative stress; however, under favorable conditions, this advantage is countered by slower reproductive development. ins-3 expression in both neurons and the intestine is downregulated in response to environmental stressors. Conversely, the neurohormone tyramine, which is released during the acute flight response, triggers an upregulation in ins-3 expression. Moreover, we found that tyramine negatively impacts environmental stress resistance by stimulating the release of INS-3 from the intestine. The subsequent release of INS-3 systemically activates the DAF-2 pathway, resulting in the inhibition of cytoprotective mechanisms mediated by DAF-16/FOXO and HSF-1. These studies offer mechanistic insights into the brain-gut communication pathway that weighs adaptive strategies to respond to acute and long-term stress scenarios.

Association of pesticide exposure with neurobehavioral outcomes among avocado farmworkers in Mexico.

BACKGROUND AND AIM: To date, few studies have focused on the health effects of pesticide exposure among avocado farmworkers. We examined the association of exposure to insecticides, fungicides, and herbicides with cognitive and mental health outcomes among these avocado workers from Michoacan, Mexico. MATERIALS AND METHODS: We conducted a cross-sectional study of 105 avocado farmworkers between May and August 2021. We collected data on self-reported pesticide use during the 12 months prior to the baseline survey and estimated annual exposure-intensity scores (EIS) using a semi-quantitative exposure algorithm. We calculated specific gravity adjusted average concentrations of 12 insecticide, fungicide, or herbicide metabolites measured in urine samples collected during two study visits (8-10 weeks apart). We assessed participants' cognitive function and psychological distress using the NIH Toolbox Cognition Battery and the Brief Symptom Inventory 18 (BSI-18), respectively. We examined individual associations of EIS and urinary pesticide metabolites with neurobehavioral outcomes using generalized linear regression models. We also implemented Bayesian Weighted Quantile Sum (BWQS) regression to evaluate the association between a pesticide metabolite mixture and neurobehavioral outcomes. RESULTS: In individual models, after adjusting for multiple comparisons, higher concentrations of hydroxy-tebuconazole (OH-TEB, metabolite of fungicide tebuconazole) were associated with higher anxiety (IRR per two-fold increase in concentrations = 1.26, 95% CI:1.08, 1.48) and Global Severity Index (GSI) (IRR = 1.89, 95% CI:1.36, 2.75) scores, whereas higher concentrations of 3,5,6-trichloro-2-pyridinol (TCPy, metabolite of chlorpyrifos) were associated with lower GSI scores (IRR = 0.69, 95% CI: 0.56, 0.85). In BWQS analyses, we found evidence of a mixture association of urinary pesticide metabolites with higher anxiety (IRR = 1.72, 95% CrI: 1.12, 2.55), depression (IRR = 4.60, 95% CrI: 2.19, 9.43), and GSI (IRR = 1.99, 95% CrI: 1.39, 2.79) scores. OH-TEB and hydroxy-thiabendazole (metabolite of fungicide thiabendazole) combined contributed 54%, 40%, and 54% to the mixture effect in the anxiety symptoms, depression symptoms, and overall psychological distress models, respectively. CONCLUSIONS: We found that exposure to tebuconazole and thiabendazole, fungicides whose effects have been rarely studied in humans, may be associated with increased psychological distress among avocado farmworkers. We also observed that exposure to chlorpyrifos may be associated with decreased psychological distress.

Integrating Data Across Multiple Sites in the Northeastern United States to Examine Associations Between a Prenatal Metal Mixture and Child Cognition.

We applied a novel hierarchical Bayesian weighted quantile sum (HBWQS) regression to combine data across 3 study sites to examine associations between prenatal exposure to metals and cognitive functioning in childhood. Data from 326 mother-child dyads enrolled in an ongoing cohort study, the Programming of Intergenerational Stress Mechanisms (PRISM) Study, based in New York, New York (recruitment in 2013-2020) and Boston, Massachusetts (recruitment 2011-2013), and the First Thousand Days of Life (FTDL) cohort study (recruitment 2012-2019), based in northern Virginia, were used. Arsenic, cadmium, manganese, lead, and antimony were measured in urine collected during pregnancy. Cognitive functioning was assessed in children aged 3-11 years using the National Institutes of Health Toolbox Cognition Battery. The HBWQS regression showed a negative association between the urinary metal mixture and the Cognition Early Childhood Composite Score in the PRISM New York City (ß = -3.67, 95% credible interval (CrI): -7.61, -0.01) and FTDL (ß = -3.76, 95% CrI: -7.66, -0.24) samples, with a similar trend in the PRISM Boston sample (ß = -3.24, 95% CrI: -6.77, 0.144). We did not detect these associations in traditionally pooled models. HBWQS regression allowed us to account for site heterogeneity and detect associations between prenatal metal-mixture exposure and cognitive outcomes in childhood. Given the ubiquity of metals exposure, interventions aimed at reducing prenatal exposure may improve cognitive outcomes in children. This article is part of a Special Collection on Environmental Epidemiology.

Recent ambient temperature and fine particulate matter (PM2.5) exposure is associated with urinary kidney injury biomarkers in children.

BACKGROUND: Limited research has examined associations between exposure to ambient temperature, air pollution, and kidney function or injury during the preadolescent period. We examined associations between exposure to ambient temperature and particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5) with preadolescent estimated glomerular filtration rate (eGFR) and urinary kidney injury biomarkers. METHODS: Participants included 437 children without cardiovascular or kidney disease enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors birth cohort study in Mexico City. eGFR and urinary kidney injury biomarkers were assessed at 8-12 years. Validated satellite-based spatio-temporal models were used to estimate mean daily temperature and PM2.5 levels at each participant's residence 7- and 30-days prior to the date of visit. Linear regression and distributed lag nonlinear models (DLNM) were used to examine associations between daily mean temperature and PM2.5 exposure and kidney outcomes, adjusted for covariates. RESULTS: In single linear regressions, higher seven-day average PM2.5 was associated with higher urinary alpha-1-microglobulin and eGFR. In DLNM analyses, higher temperature exposure in the seven days prior to date of visit was associated with a decrease in urinary cystatin C of -0.56 ng/mL (95 % confidence interval (CI): -1.08, -0.04) and in osteopontin of -0.08 ng/mL (95 % CI: -0.15, -0.001). PM2.5 exposure over the seven days prior to date of visit was associated with an increase in eGFR of 1.77 mL/min/1.73m2 (95 % CI: 0.55, 2.99) and urinary cystatin C of 0.19 ng/mL (95 % CI: 0.03, 0.35). CONCLUSIONS: Recent exposure to ambient temperature and PM2.5 were associated with increased and decreased urinary kidney injury biomarkers that may reflect subclinical glomerular or tubular injury in children. Further research is required to assess environmental exposures and worsening subclinical kidney injury across development.

Urban Stress and its Association with Symptoms of Depression, Fatigue, and Sleep Disruption in Women in Mexico City.

Women in urban neighborhoods often face disproportionately higher levels of environmental and social stressors; however, the health effects from urban stressors remains poorly understood. We aimed to evaluate the association between urban stress and symptoms of depression, fatigue, and sleep disruption in a cohort of 460 women in Mexico City. To assess urban stress, women were administered the Urban Annoyances (Nuisances Environnementales) scale. Six constructs were summarized to create an overall index. Depressive symptoms were assessed using the Edinburgh Depression Scale; the Patient-Reported Outcomes Information System scales were used to assess sleep disruption and fatigue. Linear regression models were used to estimate the association with continuous symptoms comparing women with high urban stress to those with lower levels. Models were adjusted for socioeconomic status, education, age, social support, and previous depressive symptoms. High urban stress was associated with greater depressive symptoms (ß: 1.77; 95%CI: 0.83, 2.71), fatigue (ß: 2.47; 95%CI: 0.87, 4.07), and sleep disruption (ß: 2.14; 95%CI: 0.54, 3.73). Urban stress plays an important role in women's psychological and physical health, highlighting the importance of including these measures in environmental health studies. Urban interventions, such as promoting alternative transport options, should additionally be addressed to improve health of urban populations.

Associations between early-life exposure to PM2.5 and reductions in childhood lung function in two North American longitudinal pregnancy cohort studies.

Data integration of epidemiologic studies across different geographic regions can provide enhanced exposure contrast and statistical power to examine adverse respiratory effects of early-life exposure to particulate matter <2.5 microns in diameter (PM2.5). Methodological tools improve our ability to combine data while more fully accounting for study heterogeneity. Methods: Analyses included children enrolled in two longitudinal birth cohorts in Boston, Massachusetts, and Mexico City. Propensity score matching using the 1:3 nearest neighbor with caliper method was used. Residential PM2.5 exposure was estimated from 2 months before birth to age 6 years using a validated satellite-based spatiotemporal model. Lung function was tested at ages 6-11 years and age, height, race, and sex adjusted z scores were estimated for FEV1, FVC, FEF25-75%, and FEV1/FVC. Using distributed lag nonlinear models, we examined associations between monthly averaged PM2.5 levels and lung function outcomes adjusted for covariates, in unmatched and matched pooled samples. Results: In the matched pooled sample, PM2.5 exposure between postnatal months 35-44 and 35-52 was associated with lower FEV1 and FVC z scores, respectively. A 5 µg/m3 increase in PM2.5 was associated with a reduction in FEV1 z score of 0.13 (95% CI = -0.26, -0.01) and a reduction in FVC z score of 0.13 (95% CI = -0.25, -0.01). Additionally PM2.5 during postnatal months 23-39 was associated with a reduction in FEF25-75% z score of 0.31 (95% CI = -0.57, -0.05). Conclusions: Methodological tools enhanced our ability to combine multisite data while accounting for study heterogeneity. Ambient PM2.5 exposure in early childhood was associated with lung function reductions in middle childhood.

Changes in depressive and anxiety symptoms during COVID-19 in children from the PROGRESS cohort.

BACKGROUND: We assessed associations between maternal stress, social support, and child resiliency during the COVID-19 pandemic in relation to changes in anxiety and depression symptoms in children in Mexico City. METHODS: Participants included 464 mother-child pairs from a longitudinal birth cohort in Mexico City. At ages 8-11 (pre-COVID, 2018-2019) and 9-12 (during COVID, May-Nov 2020) years, depressive symptoms were assessed using the child and parent-reported Children's Depressive Inventory. Anxiety symptoms were assessed using the child-reported Revised Manifest Anxiety Scale. Linear regression models were used to estimate associations between maternal stress, social support, and resiliency in relation to changes in depressive and anxiety symptoms. We additionally assessed outcomes using clinically relevant cut-points. Models were adjusted for child age and sex and maternal socioeconomic status and age. RESULTS: Higher continuous maternal stress levels during the COVID-19 pandemic were associated with increases in depressive symptoms (ß: 0.72; 95% CI: 0.12, 1.31), and higher odds of clinically relevant depressive and anxiety symptoms in the children. CONCLUSIONS: Maternal stress during the pandemic may increase mental health symptoms in pre-adolescent children. Additional studies are needed that examine the long-term pandemic-related impacts on mental health throughout the adolescent years. IMPACT: In this longitudinal cohort study of children in Mexico City, we observed that depressive symptoms were higher from before to during the pandemic. Maternal stress surrounding the pandemic may increase mental health symptoms in pre-adolescent children. Child resiliency may help to protect against pandemic-related stressors.

Longitudinal assessment of maternal depression and early childhood asthma and wheeze: Effect modification by child sex.

BACKGROUND: Studies report associations between maternal mental health and adverse respiratory outcomes in children; however, the impact of timing and duration of maternal distress remains understudied. We sought to longitudinally examine associations between maternal depression and childhood asthma and wheeze, and explore sex differences. METHODS: Maternal depression (n = 601) was assessed using the Edinburgh Depression Scale questionnaire, dichotomized at a clinically relevant cutoff (>12) (a) during pregnancy, (b) postpartum, and (c) postpartum and subsequent time points postnatally (recurrent depression). Report of wheeze in the past 12 months (current wheeze) and asthma were obtained using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire at 48 and 72 months. Associations were analyzed using a modified Poisson regression adjusted for covariates, and in interaction models. RESULTS: Both postpartum and recurrent depression were associated with higher risk of current wheeze (relative risk [RR]: 1.87, 95% confidence interval [CI]: 1.21, 2.90; RR: 2.41, 95% CI: 1.53, 3.79) and asthma at 48 months (RR: 2.42, 95% CI: 1.01, 5.84; RR: 2.45, 95% CI: 1.02, 5.84). In interaction analyses, associations were stronger in females. Recurrent depression was associated with a higher risk of current wheeze at 48 months in females (RR: 4.34, 95% CI: 2.02, 9.32) when compared to males (RR: 1.89, 95% CI: 1.05, 3.39). CONCLUSIONS: Postpartum and recurrent depression were associated with a higher risk of wheeze and asthma in children. Understanding the temporal- and sex-specific effects of maternal depression may better inform prevention strategies.

Síndrome inflamatorio multisistémico post-COVID en niños: reporte de casos en Montevideo, Uruguay, 2020-2021 / Multsystemic inflammatory syndrome in post-Covid children: clinical case studies in Montevideo, Uruguay, 2020-2021 / Sindrome inflamatório multisistêmico pós-COVID em crianças: relato de casos em Montevdéu, Uruguai, 2020-2021

El síndrome inflamatorio multisistémico asociado a COVID-19 es una presentación postinfecciosa, que puede ser particularmente grave, pudiendo producir una severa disfunción multiorgánica. Se presenta una serie de 6 casos clínicos, asistidos en Servicio Médico Integral, Montevideo-Uruguay, con el fin de exponer las características clínicas y paraclínicas de este nuevo síndrome, y la evolución clínica de los mismos. Se realiza un estudio observacional descriptivo. La edad media fue de 6 años, con predominio en sexo femenino. Estos pacientes tuvieron una presentación clínica leve a moderada, con buena evolución Las manifestaciones clínicas principales fueron: fiebre, compromiso gastrointestinal, mucocutáneo y afectación ocular; dos de estos pacientes presentaron compromiso cardiovascular. Todos tuvieron alteraciones en la paraclínica, destacándose reactantes de fase aguda elevados. Todos los pacientes recibieron inmunoglobulina intravenosa y corticoides, tres de ellos recibieron heparina de bajo peso molecular por valor de D-dímeros 5 veces por encima del valor de referencia. No descartamos el impacto del diagnóstico y tratamiento precoz en la buena evolución de estos niños.

The Multisystem Inflammatory Syndrome associated with COVID-19 is a postinfectious presentation, which can be particularly serious, and can produce severe multiorgan dysfunction. A report of 6 clinical cases, assisted in the Comprehensive Medical Service, Montevideo-Uruguay, is presented in order to expose the clinical and paraclinical characteristics of this new syndrome, and their clinical evolution. A descriptive observational study was carried out. The mean age was 6 years, with a predominance of females. These patients had a mild to moderate clinical presentation, with good evolution. The main clinical manifestations were: fever, gastrointestinal and mucocutaneous involvement, and ocular involvement; two of these patients had cardiovascular compromise. All had alterations in the paraclinical, standing out elevated acute phase reactants. All patients received intravenous immunoglobulin and corticosteroids, three of them received low molecular weight heparin with a value of D-dimers 5 times higher than the reference value. We do not rule out the impact of early diagnosis and treatment on the positive evolution of these children.

A Síndrome Inflamatória Multissistêmica associada à COVID-19 é uma apresentação pósinfecciosa, que pode ser particularmente grave e produzir disfunção grave de múltiplos órgãos. Apresentamos um relato de 6 casos clínicos, atendidos no Serviço Médico Integral, Montevidéu-Uruguai, com o objetivo de expor as características clínicas e para clínicas desta nova síndrome, e sua evolução clínica. Tratase de um estudo observacional descritivo. A média de idade foi de 6 anos, com predomínio do sexo feminino. Esses pacientes tinham apresentação clínica leve a moderada, com boa evolução. As principais manifestações clínicas foram: febre, envolvimento gastrointestinal, muco cutâneo e ocular; dois desses pacientes apresentaram comprometimento cardiovascular. Todos apresentavam alterações para clínicas, destacandose elevados reagentes na fase aguda. Todos os pacientes receberam imunoglobulina e corticosteroides endovenosos, três deles receberam heparina de baixo peso molecular com valor do dímero D 5 vezes acima do valor de referência. Não descartamos o impacto do diagnóstico e tratamento precoces na evolução positiva dessas crianças.

Prenatal Metal Exposures and Associations with Kidney Injury Biomarkers in Children.

Prenatal exposure to arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) may be nephrotoxic, yet limited studies have examined subclinical kidney injury biomarkers in children. We assessed whether metal exposure in the second trimester (2T), a crucial time of kidney development, is associated with altered urine kidney injury and function biomarkers in preadolescent children. Analyses included 494 children participating in a birth cohort study in Mexico City. Concentrations of As, Cd, and Pb were measured from pregnant women in 2T blood and urine, and Hg in urine only. Kidney biomarkers were measured from children in urine at age 8-12 years. We assessed the associations between individual metals and (1) kidney biomarkers using linear regression and (2) a multi-protein kidney mixture using weighted quantile sum (WQS) regression. Associations of separate urine and blood metal mixtures with individual kidney biomarkers were assessed via WQS. Within the multi-protein mixture, the association with increased urinary As was predominated by urine alpha-1-microglobulin (A1M), interferon gamma-induced protein 10 (IP10), and fatty acid binding protein 1; the association with increased urinary Cd was predominated by A1M, clusterin, and albumin. The urine metal mixture was associated with increased albumin (0.23 ng/mL; 95% confidence interval (CI): 0.10, 0.37), IP10 (0.15 ng/mL; 95% CI: 0.02, 0.28), and cystatin C (0.17 ng/mL; 95% CI: 0.04, 0.31); these associations were mainly driven by urinary As and Cd. We observed null associations between prenatal blood or urine metal mixtures and estimated glomerular filtration rate. Higher prenatal urinary metals, individually and as a mixture were associated with altered kidney injury biomarkers in children. Further research and longer participant follow-up are required to ascertain the risk of kidney disease later in life.

1-Mesityl-3-(3-Sulfonatopropyl) Imidazolium Protects Against Oxidative Stress and Delays Proteotoxicity in C. elegans.

Due to the increase in life expectancy worldwide, age-related disorders such as neurodegenerative diseases (NDs) have become more prevalent. Conventional treatments comprise drugs that only attenuate some of the symptoms, but fail to arrest or delay neuronal proteotoxicity that characterizes these diseases. Due to their diverse biological activities, imidazole rings are intensively explored as powerful scaffolds for the development of new bioactive molecules. By using C. elegans, our work aims to explore novel biological roles for these compounds. To this end, we have tested the in vivo anti-proteotoxic effects of imidazolium salts. Since NDs have been largely linked to impaired antioxidant defense mechanisms, we focused on 1-Mesityl-3-(3-sulfonatopropyl) imidazolium (MSI), one of the imidazolium salts that we identified as capable of improving iron-induced oxidative stress resistance in wild-type animals. By combining mutant and gene expression analysis we have determined that this protective effect depends on the activation of the Heat Shock Transcription Factor (HSF-1), whereas it is independent of other canonical cytoprotective molecules such as abnormal Dauer Formation-16 (DAF-16/FOXO) and Skinhead-1 (SKN-1/Nrf2). To delve deeper into the biological roles of MSI, we analyzed the impact of this compound on previously established C. elegans models of protein aggregation. We found that MSI ameliorates ß-amyloid-induced paralysis in worms expressing the pathological protein involved in Alzheimer's Disease. Moreover, this compound also delays age-related locomotion decline in other proteotoxic C. elegans models, suggesting a broad protective effect. Taken together, our results point to MSI as a promising anti-proteotoxic compound and provide proof of concept of the potential of imidazole derivatives in the development of novel therapies to retard age-related proteotoxic diseases.