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1.
Environ Res ; 204(Pt B): 112062, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34537199

RESUMO

Air pollution exposure, especially particulate matter ≤2.5 µm in diameter (PM2.5), is associated with poorer kidney function in adults and children. Perinatal exposure may occur during susceptible periods of nephron development. We used distributed lag nonlinear models (DLNMs) to examine time-varying associations between early life daily PM2.5 exposure (periconceptional through age 8 years) and kidney parameters in preadolescent children aged 8-10 years. Participants included 427 mother-child dyads enrolled in the PROGRESS birth cohort study based in Mexico City. Daily PM2.5 exposure was estimated at each participant's residence using a validated satellite-based spatio-temporal model. Kidney function parameters included estimated glomerular filtration rate (eGFR), serum cystatin C, and blood urea nitrogen (BUN). Models were adjusted for child's age, sex and body mass index (BMI) z-score, as well as maternal education, indoor smoking report and seasonality (prenatal models were additionally adjusted for average first year of life PM2.5 exposure). We also tested for sex-specific effects. Average perinatal PM2.5 was 22.7 µg/m3 and ranged 16.4-29.3 µg/m3. Early pregnancy PM2.5 exposures were associated with higher eGFR in preadolescence. Specifically, we found that PM2.5 exposure between weeks 1-18 of gestation was associated with increased preadolescent eGFR, whereas exposure in the first 14 months of life after birth were associated with decreased eGFR. Specifically, a 5 µg/m3 increase in PM2.5 during the detected prenatal window was associated with a cumulative increase in eGFR of 4.44 mL/min/1.732 (95%CI: 1.37, 7.52), and during the postnatal window we report a cumulative eGFR decrease of -10.36 mL/min/1.732 (95%CI: -17.68, -3.04). We identified perinatal windows of susceptibility to PM2.5 exposure with preadolescent kidney function parameters. Follow-up investigating PM2.5 exposure with peripubertal kidney function trajectories and risk of kidney disease in adulthood will be critical.

2.
Epigenetics ; : 1-18, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34569420

RESUMO

DNA methylation (DNAm) is vulnerable to dysregulation by environmental exposures during epigenetic reprogramming that occurs in embryogenesis. Sexual dimorphism in environmentally induced DNAm dysregulation has been identified and therefore it is important to understand sex-specific DNAm patterns. DNAm at several autosomal sites has been consistently associated with sex in cord blood and placental foetal tissues. However, there is limited research comparing sex-specific DNAm across tissues, particularly differentially methylated regions (DMRs). This study leverages DNAm data measured using the Illumina HumanMethylation450 BeadChip in cord blood (N = 179), placenta (N = 229), and umbilical artery samples (N = 229) in the PRogramming of Intergenerational Stress Mechanisms (PRISM) cohort to identify autosomal DMRs and differentially methylated positions (DMPs). A replication analyses was conducted in an independent cohort (GEO Accession GSE129841). We identified 183, 257, and 419 DMRs and 2119, 2281, and 3405 DMPs (pBonferroni < 0.05) in cord blood, placenta, and artery samples, respectively. Thirty-nine DMRs overlapped in all three tissues, overlapping with genes involved in spermatogenesis (NKAPL, PIWIL2 and AURKC) and X-inactivation (LRIF1). In replication analysis, 85% of DMRs overlapped with those identified in PRISM. Overall, DMRs and DMPs had higher methylation levels among females in cord blood and artery samples, but higher methylation levels among males in placenta samples. Further research is necessary to understand biological mechanisms that contribute to differences in sex-specific DNAm signatures across tissues, as well as to determine if sexual dimorphism in the epigenome impacts response to environmental stressors.

3.
Clin Epigenetics ; 13(1): 121, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078457

RESUMO

BACKGROUND: The difference between an individual's chronological and DNA methylation predicted age (DNAmAge), termed DNAmAge acceleration (DNAmAA), can capture life-long environmental exposures and age-related physiological changes reflected in methylation status. Several studies have linked DNAmAA to morbidity and mortality, yet its relationship with kidney function has not been assessed. We evaluated the associations between seven DNAm aging and lifespan predictors (as well as GrimAge components) and five kidney traits (estimated glomerular filtration rate [eGFR], urine albumin-to-creatinine ratio [uACR], serum urate, microalbuminuria and chronic kidney disease [CKD]) in up to 9688 European, African American and Hispanic/Latino individuals from seven population-based studies. RESULTS: We identified 23 significant associations in our large trans-ethnic meta-analysis (p < 1.43E-03 and consistent direction of effect across studies). Age acceleration measured by the Extrinsic and PhenoAge estimators, as well as Zhang's 10-CpG epigenetic mortality risk score (MRS), were associated with all parameters of poor kidney health (lower eGFR, prevalent CKD, higher uACR, microalbuminuria and higher serum urate). Six of these associations were independently observed in European and African American populations. MRS in particular was consistently associated with eGFR (ß = - 0.12, 95% CI = [- 0.16, - 0.08] change in log-transformed eGFR per unit increase in MRS, p = 4.39E-08), prevalent CKD (odds ratio (OR) = 1.78 [1.47, 2.16], p = 2.71E-09) and higher serum urate levels (ß = 0.12 [0.07, 0.16], p = 2.08E-06). The "first-generation" clocks (Hannum, Horvath) and GrimAge showed different patterns of association with the kidney traits. Three of the DNAm-estimated components of GrimAge, namely adrenomedullin, plasminogen-activation inhibition 1 and pack years, were positively associated with higher uACR, serum urate and microalbuminuria. CONCLUSION: DNAmAge acceleration and DNAm mortality predictors estimated in whole blood were associated with multiple kidney traits, including eGFR and CKD, in this multi-ethnic study. Epigenetic biomarkers which reflect the systemic effects of age-related mechanisms such as immunosenescence, inflammaging and oxidative stress may have important mechanistic or prognostic roles in kidney disease. Our study highlights new findings linking kidney disease to biological aging, and opportunities warranting future investigation into DNA methylation biomarkers for prognostic or risk stratification in kidney disease.

4.
Pulm Circ ; 11(2): 20458940211019626, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34104425

RESUMO

Eleven participants with COVID-19 acute respiratory distress syndrome requiring mechanical ventilation underwent pulmonary artery catheterization for clinical indications. Clinical interventions or events concurrent with hemodynamic were recorded. Increased cardiac index was associated with worse hypoxemia. Modulation of cardiac index may improve hypoxemia in patients with COVID-19 acute respiratory distress syndrome.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34063533

RESUMO

Occupational and non-occupational risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported in healthcare workers (HCWs), but studies evaluating risk factors for infection among physician trainees are lacking. We aimed to identify sociodemographic, occupational, and community risk factors among physician trainees during the first wave of coronavirus disease 2019 (COVID-19) in New York City. In this retrospective study of 328 trainees at the Mount Sinai Health System in New York City, we administered a survey to assess risk factors for SARS-CoV-2 infection between 1 February and 30 June 2020. SARS-CoV-2 infection was determined by self-reported and laboratory-confirmed IgG antibody and reverse transcriptase-polymerase chain reaction test results. We used Bayesian generalized linear mixed effect regression to examine associations between hypothesized risk factors and infection odds. The cumulative incidence of infection was 20.1%. Assignment to medical-surgical units (OR, 2.51; 95% CI, 1.18-5.34), and training in emergency medicine, critical care, and anesthesiology (OR, 2.93; 95% CI, 1.24-6.92) were independently associated with infection. Caring for unfamiliar patient populations was protective (OR, 0.16; 95% CI, 0.03-0.73). Community factors were not statistically significantly associated with infection after adjustment for occupational factors. Our findings may inform tailored infection prevention strategies for physician trainees responding to the COVID-19 pandemic.


Assuntos
COVID-19 , Médicos , Teorema de Bayes , Pessoal de Saúde , Humanos , Cidade de Nova Iorque/epidemiologia , Pandemias , Estudos Retrospectivos , SARS-CoV-2
6.
Environ Int ; 156: 106714, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34147999

RESUMO

BACKGROUND: Prenatal exposure to metals has been individually associated with birth outcomes. However, little is known about the effect of metal mixture, particularly at low exposure levels. OBJECTIVES: To estimate individual and joint effects of metal mixture components on birth outcomes. METHODS: We used data from 1,391 mother-infant pairs in Project Viva (1999-2002). We measured 11 metals in maternal 1st trimester erythrocyte; abstracted birth weight from medical records; calculated gestational age from last menstrual period or ultrasound; and obtained birth length (n = 729) and head circumference (n = 791) from research measurements. We estimated individual and joint effects of metals using multivariable linear and Bayesian kernel machine regressions. RESULTS: In both single metal and metal mixture analyses, exposure to higher concentrations of arsenic was associated with lower birth weight in males, zinc with higher head circumference in females, and manganese with higher birth length in sex-combined analysis. We also observed sex-specific metal interactions with birth outcomes. Arsenic and manganese showed a synergistic association with birth weight in males, in whom an interquartile range (IQR) increase in arsenic was associated with 25.3 g (95% CI: -79.9, 29.3), 47.9 g (95% CI: -98.0, 2.1), and 72.2 g (95% CI: -129.8, -14.7) lower birth weight when manganese concentrations were at 25th, 50th, and 75th percentiles, respectively. Lead and zinc showed an antagonistic association with head circumference in males, where an IQR increase in lead was associated with 0.18 cm (95% CI: -0.35, -0.02), 0.10 cm (95% CI: -0.25, 0.04), 0.03 cm (95% CI: -0.2, 0.14) smaller head circumference when zinc concentrations were at 25th, 50th, and 75th percentiles, respectively. Exposure to higher concentrations of arsenic was also associated with lower gestational age in males when concentrations of manganese and lead were higher. DISCUSSION: Maternal erythrocyte concentrations of arsenic, manganese, lead, and zinc were individually and interactively associated with birth outcomes. The associations varied by infant sex and exposure level of other mixture components.


Assuntos
Arsênio , Arsênio/análise , Arsênio/toxicidade , Teorema de Bayes , Peso ao Nascer , Feminino , Idade Gestacional , Humanos , Lactente , Masculino , Exposição Materna/efeitos adversos , Gravidez , Estudos Prospectivos
7.
Mitochondrion ; 59: 267-275, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34102325

RESUMO

Mitochondria fuel placental activity, with mitochondrial dysfunction implicated in several perinatal complications. We investigated placental mtDNA mutational load using NextGen sequencing in relation to birthweight and gestational length among 358 mother-newborn pairs. We found that higher heteroplasmy, especially in the hypervariable displacement loop region, was associated with shorter gestational length. Results were similar among male and female pregnancies, but stronger in magnitude among females. With regard to growth, we observed that higher mutational load was associated with lower birthweight-for-gestational age (BWGA) among females, but higher BWGA among males. These findings support potential sex-differential fetal biological strategies for coping with increased heteroplasmies.

8.
Nat Commun ; 12(1): 3692, 2021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-34140520

RESUMO

The COVID-19 pandemic has yielded disproportionate impacts on communities of color in New York City (NYC). Researchers have noted that social disadvantage may result in limited capacity to socially distance, and consequent disparities. We investigate the association between neighborhood social disadvantage and the ability to socially distance, infections, and mortality in Spring 2020. We combine Census Bureau and NYC open data with SARS-CoV-2 testing data using supervised dimensionality-reduction with Bayesian Weighted Quantile Sums regression. The result is a ZIP code-level index with weighted social factors associated with infection risk. We find a positive association between neighborhood social disadvantage and infections, adjusting for the number of tests administered. Neighborhood disadvantage is also associated with a proxy of the capacity to socially isolate, NYC subway usage data. Finally, our index is associated with COVID-19-related mortality.


Assuntos
COVID-19/epidemiologia , Ferrovias/estatística & dados numéricos , Características de Residência , Afro-Americanos/estatística & dados numéricos , Teorema de Bayes , COVID-19/mortalidade , Estudos Transversais , Disparidades nos Níveis de Saúde , Humanos , Cidade de Nova Iorque/epidemiologia , Distanciamento Físico , Densidade Demográfica , Fatores Socioeconômicos
9.
Environ Res ; 201: 111338, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34051199

RESUMO

BACKGROUND: Phthalate exposure has been associated with increased childhood behavioral problems. Existing studies failed to include phthalate replacements and did not account for high correlations among phthalates. Phthalates' exposure is higher in Mexico than in U.S. locations, making it an ideal target population for this study. AIM: To examine associations between 15 maternal prenatal phthalate metabolite concentrations and children's behavioral problems. METHODS: We quantified phthalate metabolites in maternal urine samples from maternal-child dyads (n = 514) enrolled in the Programming Research in Obesity, Growth Environment and Social Stress (PROGRESS) birth cohort in Mexico City. We performed least absolute shrinkage and selection operator (LASSO) regressions to identify associations between specific-gravity adjusted log2-transformed phthalate metabolites and parent-reported 4-6 year old behavior on the Behavior Assessment System for Children (BASC-2), accounting for metabolite correlations. We adjusted for socio-demographic and birth-related factors, and examined associations stratified by sex. RESULTS: Higher prenatal mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) urinary concentrations were associated with increased hyperactivity scores in the overall sample (ß = 0.57, 95% CI = 0.17, 1.13) and in girls (ß = 0.54, 95% CI = 0.16, 1.08), overall behavioral problems in boys (ß = 0.58, 95% CI = 0.20, 1.15), and depression scores in boys (ß = 0.44, 95% CI = 0.06, 0.88). Higher prenatal monobenzyl phthalate (MBzP) concentrations were associated with reduced hyperactivity scores in girls (ß = -0.54, 95% CI = -1.08, -0.21). DISCUSSION: Our findings suggested that prenatal concentrations of phthalates and their replacements altered child neurodevelopment and those associations may be influenced sex.


Assuntos
Ácidos Ftálicos/urina , Efeitos Tardios da Exposição Pré-Natal , Comportamento Problema , Criança , Pré-Escolar , Feminino , Humanos , Masculino , México , Obesidade , Gravidez , Estresse Psicológico
10.
Environ Int ; 155: 106612, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33965768

RESUMO

BACKGROUND: Pregnancy induces numerous cardiovascular and metabolic changes. Alterations in these sensitive processes may precipitate long-term post-delivery health consequences. Studies have reported associations between phthalates and metabolic complications of pregnancy, but no study has investigated metabolic outcomes beyond pregnancy. OBJECTIVES: To examine associations of exposure to phthalates during pregnancy with post-delivery metabolic health. DESIGN: We quantified 15 urinary phthalate biomarker concentrations during the second and third trimesters among 618 pregnant women from Mexico City. Maternal metabolic health biomarkers included fasting blood measures of glycemia [glucose, insulin, Homeostatic Model Assessment of Insulin Resistance [HOMA-IR], % hemoglobin A1c (HbA1c%)] and lipids (total, high-density lipoprotein (HDL), low-density lipoprotein (LDL) cholesterol, triglycerides), at 4-5 and 6-8 years post-delivery. To estimate the influence of the phthalates mixture, we used Bayesian weighted quantile sum regression and Bayesian kernel machine regression; for individual biomarkers, we used linear mixed models. RESULTS: As a mixture, higher urinary phthalate biomarker concentrations during pregnancy were associated with post-delivery concentrations of plasma glucose (interquartile range [IQR] difference: 0.13 SD, 95%CrI: 0.05, 0.20), plasma insulin (IQR difference: 0.06 SD, 95%CrI: -0.02, 0.14), HOMA-IR (IQR difference: 0.08 SD, 95% CrI: 0.01, 0.16), and HbA1c% (IQR difference: 0.15 SD, 95%CrI: 0.05, 0.24). Associations were primarily driven by mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) and the sum of dibutyl phthalate biomarkers (∑DBP). The phthalates mixture was associated with lower HDL (IQR difference: -0.08 SD, 95%CrI: -0.16, -0.01), driven by ∑DBP and monoethyl phthalate (MEP), and higher triglyceride levels (IQR difference: 0.15 SD, 95%CrI: 0.08, 0.22), driven by MECPTP and MEP. The overall mixture was not associated with total cholesterol and LDL. However, ∑DBP and MEP were associated with lower and higher total cholesterol, respectively, and MECPTP and ∑DBP were associated with lower LDL. CONCLUSIONS: Phthalate exposure during pregnancy is associated with adverse long-term changes in maternal metabolic health. A better understanding of timing of the exact biological changes and their implications on metabolic disease risk is needed.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Teorema de Bayes , Biomarcadores , Glicemia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Poluentes Ambientais/toxicidade , Feminino , Humanos , Lipídeos , Ácidos Ftálicos/toxicidade , Gravidez
11.
Environ Epidemiol ; 5(2): e147, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33870019

RESUMO

Prenatal exposure to metals has been associated with a range of adverse neurocognitive outcomes; however, associations with early behavioral development are less well understood. We examined joint exposure to multiple co-occurring metals in relation to infant negative affect, a stable temperamental trait linked to psychopathology among children and adults. Methods: Analyses included 308 mother-infant pairs enrolled in the PRISM pregnancy cohort. We measured As, Ba, Cd, Cs, Cr, Pb, and Sb in urine, collected on average during late pregnancy, by ICP-MS. At age 6 months, we assessed negative affect using the Infant Behavior Questionnaire-Revised. We used Weighted Quantile Sum (WQS) regression with repeated holdout validation to estimate the joint association between the metals and global negative affectivity, as well as four subdomains (Fear, Sadness, Distress to Limitations, and Falling Reactivity). We also tested for a sex interaction with estimated stratified weights. Results: In adjusted models, urinary metals were associated with higher scores on the Fear scale (ßWQS = 0.20, 95% confidence interval [CI]: 0.09, 0.30), which captures behavioral inhibition, characterized by startle or distress to sudden changes in the environment and inhibited approach to novelty. We observed a significant sex interaction (95% CI for the cross-product term: -0.19, -0.01), and stratified weights showed girls (61.6%) contributed substantially more to the mixture effect compared with boys (38.4%). Overall, Ba contributed the greatest mixture weight (22.5%), followed by Cs (14.9%) and As (14.6%). Conclusions: Prenatal exposure to metals was associated with increased infant scores on the temperamental domain of fear, with girls showing particular sensitivity.Key words: Prenatal; Metals; Mixtures; Temperament; Infancy; Negative affect.

12.
Environ Res ; 197: 111131, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33865819

RESUMO

The adverse effects of fine particulate matter (PM) and many volatile organic compounds (VOCs) on human health are well known. Fine particles are, in fact, those most capable of penetrating in depth into the respiratory system. People spend most of their time indoors where concentrations of some pollutants are sometimes higher than outdoors. Therefore, there is the need to ensure a healthy indoor environment and for this purpose the use of an air purifier can be a valuable aid especially now since it was demonstrated that indoor air quality has a high impact on spreading of viral infections such as that due to SARS-COVID19. In this study, we tested a commercial system that can be used as an air purifier. In particular it was verified its efficiency in reducing concentrations of PM10 (particles with aerodynamic diameter less than 10 µm), PM2.5 (particles with aerodynamic diameter less than 2.5 µm), PM1 (particles with aerodynamic diameter less than 1 µm), and particles number in the range 0.3 µm-10 µm. Furthermore, its capacity in reducing VOCs concentration was also checked. PM measurements were carried out by means of a portable optical particle counter (OPC) instrument simulating the working conditions typical of a household environment. In particular we showed that the tested air purifier significantly reduced both PM10 and PM2.5 by 16.8 and 7.25 times respectively that corresponds to a reduction of about 90% and 80%. A clear reduction of VOCs concentrations was also observed since a decrease of over 50% of these gaseous substances was achieved.


Assuntos
Filtros de Ar , Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , COVID-19 , Compostos Orgânicos Voláteis , Aerossóis , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Monitoramento Ambiental , Humanos , Tamanho da Partícula , Material Particulado/análise , SARS-CoV-2 , Compostos Orgânicos Voláteis/análise
13.
J Aging Health ; 33(7-8): 531-544, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33706594

RESUMO

Objectives: To develop and validate a clinical frailty index to characterize aging among responders to the 9/11 World Trade Center (WTC) attacks. Methods: This study was conducted on health monitoring data on a sample of 6197 responders. A clinical frailty index, WTC FI-Clinical, was developed according to the cumulative deficit model of frailty. The validity of the resulting index was assessed using all-cause mortality as an endpoint. Its association with various cohort characteristics was evaluated. Results: The sample's median age was 51 years. Thirty items were selected for inclusion in the index. It showed a strong correlation with age, as well as significant adjusted associations with mortality, 9/11 exposure severity, sex, race, pre-9/11 occupation, education, and smoking status. Discussion: The WTC FI-Clinical highlights effects of certain risk factors on aging within the 9/11 responder cohort. It will serve as a useful instrument for monitoring and tracking frailty within this cohort.


Assuntos
Socorristas , Fragilidade , Ataques Terroristas de 11 de Setembro , Envelhecimento , Estudos de Coortes , Humanos
14.
Biol Sex Differ ; 12(1): 6, 2021 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407895

RESUMO

BACKGROUND: Fetal sex is known to modify the course and complications of pregnancy, with recent evidence of sex-differential fetal influences on the maternal immune and endocrine systems. In turn, heightened inflammation and surges in reproductive hormone levels associated with pregnancy and parturition have been linked with the development of perinatal depression. Here, we examined whether there is an association between fetal sex and maternal depression assessed during the prenatal and postnatal periods. METHODS: The study included two multi-ethnic, prospective pregnancy cohorts that enrolled women from prenatal clinics in the Northeastern United States between 2001 and 2018. Maternal depressive symptoms were measured during the prenatal and postnatal periods using the Edinburgh Postpartum Depression Scale (EPDS), and newborn sex was reported by the mother following delivery. We used logistic regression to examine associations between fetal sex and maternal depressive symptoms (EPDS > 10) during the prenatal period only, postnatal period only, or both periods versus no depressive symptoms during either period. We considered both unadjusted models and models adjusted for a core set of sociodemographic and lifestyle variables. RESULTS: In adjusted models using PRISM data (N = 528), women pregnant with a male versus female fetus had significantly greater odds of depressive symptoms during the postnatal period compared to women without depressive symptoms during either period (odds ratio [OR] = 5.24, 95% confidence interval [CI] = 1.93, 14.21). The direction of results was consistent in the ACCESS cohort, although the findings did not reach statistical significance (OR = 2.05, 95% CI = 0.86, 4.93). Significant associations were not observed in either cohort among women with prenatal symptoms only or women with prenatal and postnatal symptoms. CONCLUSIONS: Male fetal sex was associated with the onset of depressive symptoms during the postnatal period.


Assuntos
Depressão Pós-Parto , Depressão Pós-Parto/epidemiologia , Feminino , Humanos , Recém-Nascido , Masculino , Período Pós-Parto , Gravidez , Estudos Prospectivos , Caracteres Sexuais
15.
Mol Psychiatry ; 26(6): 1832-1845, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33414500

RESUMO

Maternal anxiety during pregnancy is associated with adverse foetal, neonatal, and child outcomes, but biological mechanisms remain unclear. Altered foetal DNA methylation (DNAm) has been proposed as a potential underlying mechanism. In the current study, we performed a meta-analysis to examine the associations between maternal anxiety, measured prospectively during pregnancy, and genome-wide DNAm from umbilical cord blood. Sixteen non-overlapping cohorts from 12 independent longitudinal studies of the Pregnancy And Childhood Epigenetics Consortium participated, resulting in a combined dataset of 7243 mother-child dyads. We examined prenatal anxiety in relation to genome-wide DNAm and differentially methylated regions. We observed no association between the general symptoms of anxiety during pregnancy or pregnancy-related anxiety, and DNAm at any of the CpG sites, after multiple-testing correction. Furthermore, we identify no differentially methylated regions associated with maternal anxiety. At the cohort-level, of the 21 associations observed in individual cohorts, none replicated consistently in the other cohorts. In conclusion, contrary to some previous studies proposing cord blood DNAm as a promising potential mechanism explaining the link between maternal anxiety during pregnancy and adverse outcomes in offspring, we found no consistent evidence for any robust associations between maternal anxiety and DNAm in cord blood. Larger studies and analysis of DNAm in other tissues may be needed to establish subtle or subgroup-specific associations between maternal anxiety and the foetal epigenome.


Assuntos
Metilação de DNA , Epigenoma , Ansiedade/genética , Metilação de DNA/genética , Epigênese Genética/genética , Epigenômica , Feminino , Humanos , Gravidez
16.
Exp Dermatol ; 30(8): 1197-1203, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33015854

RESUMO

Studies have examined the utility of DNA methylation as a biomarker of psoriasis treatment responses, but investigations of treatment responses with Skin-Blood DNA methylation age (SkinBloodAge)-a methylation-based measure of health designed using skin tissues-are lacking. Using a HumanMethylation450 BeadChip blood DNA methylation data set from 70 white patients who presented with moderate-to-severe plaque psoriasis and were treated with anti-tumor necrosis factor (TNF) agents in Madrid, Spain, we examined the cross-sectional relationships of SkinBloodAge with anti-TNF treatment responses. Partial responders had a 7.2-year higher mean SkinBloodAge than excellent responders (P = .03). In linear regression models adjusted for chronological age, sex and anti-TNF agents - on average - partial responders had a 2.65-year higher SkinBloodAge than excellent responders (95%CI: 0.44, 4.86, P = .02). This relationship was attenuated in a sensitivity analysis adjusting for white blood cells including known T-cell mediators of psoriasis pathophysiology (ß = 1.91-years, 95%CI: -0.50, 4.32, P = .12). Overall, our study suggests that partial responders to anti-TNF therapy have higher SkinBloodAges when compared to excellent responders. Although these findings still need to be confirmed more broadly, they further suggest that SkinBloodAge may be a useful treatment response biomarker that can be incorporated with other blood tests before anti-TNF therapy initiation in moderate-to-severe psoriasis patients.

17.
J Gerontol A Biol Sci Med Sci ; 76(5): 760-769, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33027507

RESUMO

One-carbon metabolism is an important contributor to aging-related diseases; nevertheless, relationships of one-carbon metabolites with novel DNA methylation-based measures of biological aging remain poorly characterized. We examined relationships of one-carbon metabolites with 3 DNA methylation-based measures of biological aging: DNAmAge, GrimAge, and PhenoAge. We measured plasma levels of 4 common one-carbon metabolites (vitamin B6, vitamin B12, folate, and homocysteine) in 715 VA Normative Aging Study participants with at least 1 visit between 1999 and 2008 (observations = 1153). DNA methylation age metrics were calculated using the HumanMethylation450 BeadChip. We utilized Bayesian Kernel Machine Regression models adjusted for chronological age, lifestyle factors, age-related diseases, and study visits to determine metabolites important to the aging outcomes. Bayesian Kernel Machine Regression models allowed for the estimation of the relationships of single metabolites and the cumulative metabolite mixture with methylation age. Log vitamin B6 was selected as important to PhenoAge (ß = -1.62 years, 95% CI: -2.28, -0.96). Log folate was selected as important to GrimAge (ß = 0.75 years, 95% CI: 0.41, 1.09) and PhenoAge (ß = 1.62 years, 95% CI: 0.95, 2.29). Compared to a model where each metabolite in the mixture is set to its 50th percentile, the log cumulative mixture with each metabolite at its 30th (ß = -0.13 years, 95% CI: -0.26, -0.005) and 40th percentile (ß = -0.06 years, 95% CI: -0.11, -0.005) was associated with decreased GrimAge. Our results provide novel characterizations of the relationships between one-carbon metabolites and DNA methylation age in a human population study. Further research is required to confirm these findings and establish their generalizability.


Assuntos
Envelhecimento , Metilação de DNA , Ácido Fólico/sangue , Vitamina B 6/sangue , Idoso , Envelhecimento/sangue , Envelhecimento/genética , Biomarcadores/sangue , Ilhas de CpG , Epigênese Genética , Homocisteína/sangue , Humanos , Estudos Longitudinais , Masculino , Análise de Regressão , Veteranos , Vitamina B 12/sangue
18.
Epigenetics ; 16(4): 389-404, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32777999

RESUMO

Maternal stress is associated with adverse child health. Breast milk microRNAs encapsulated in extracellular vesicles (EVs) are involved in mother-infant biochemical communication during early-life programming. We leverage the PRogramming of Intergenerational Stress Mechanisms (PRISM) pregnancy cohort to investigate associations between maternal stress and breast milk EV-microRNAs. Lifetime stress and negative life events (NLEs) during pregnancy were assessed using the Life Stressor Checklist-Revised (LSCR) and the Crisis in Family Systems-Revised surveys, respectively. RNA was extracted from breast milk EVs (N = 80; collected 6.1 ± 5.9 weeks postnatally), and microRNAs were profiled using the TaqMan OpenArray Human miRNA panel. Associations between stress scores and detection (yes/no) of 173 microRNAs identified in 20-80% of samples were assessed using logistic regression; associations with expression levels of 205 EV-microRNAs identified in >50% of samples were assessed using linear regression. In adjusted models, detection of 60 and 44 EV-microRNAs was associated with higher LSCR and NLE scores, respectively (p < 0.05). Expression level of 8 and 17 EV-microRNAs was associated with LSCR and NLE scores, respectively, at our a priori criteria of p < 0.05 and |Bregression|>0.2. Enriched KEGG pathways for microRNAs associated with stress scores included fatty acid metabolism and the Hippo signaling pathway. Maternal lifetime stress and NLEs during pregnancy were both associated with detection and expression level of breast milk EV-microRNAs, although associations with microRNA profiles differed between stress measures. Further research is needed to identify biological pathways impacted by associated microRNAs and investigate relationships with child health outcomes.Abbreviations: EV: extracellular vesicle; PRISM: PRogramming of Intergenerational Stress Mechanisms pregnancy cohort; LSCR: Life Stressor Checklist-Revised survey; NLE: negative life event; CRISYS-R: Crisis in Family Systems-Revised survey; KEGG: Kyoto Encyclopaedia of Genes and Genomes; NYC: New York City; SD: standard deviation; IQR: interquartile range; Cq: relative cycle threshold values; PCA: principal component analysis.

19.
J Expo Sci Environ Epidemiol ; 31(1): 108-116, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-31636367

RESUMO

BACKGROUND: Lead is a ubiquitous toxicant following three compartment kinetics with the longest half-life found in bones. Patella and tibia lead levels-validated measures of cumulative exposure-require specialized X-ray-fluorescence-spectroscopy available only in a few centers worldwide. We developed minimally invasive biomarkers reflecting individual cumulative lead exposure using blood DNA methylation profiles-obtainable via Illumina 450K or IlluminaEPIC bead-chip assays. METHODS: We developed and tested two methylation-based biomarkers from 348 Normative Aging Study (NAS) elderly men. We selected methylation sites with strong associations with bone lead levels via robust regressions analysis and constructed the biomarkers using elastic nets. Results were validated in a NAS subset, reporting specificity, and sensitivity. FINDINGS: Participants were 73 years old on average (standard deviation, SD = 6), with moderate lead levels of (mean ± SD patella: 27 ± 18 µg/g; tibia:21 ± 13 µg/g). Methylation-based biomarkers for lead in patella and tibia included 59 and 138 DNA methylation sites, respectively. Estimated lead levels were significantly correlated with actual measured values, (r = 0.62 patella, r = 0.59 tibia) and had low mean square error (MSE) (MSE = 0.68 patella, MSE = 0.53 tibia). Means and distributions of the estimated and actual lead levels were not significantly different across patella and tibia bones (p > 0.05). Methylation-based biomarkers discriminated participants highly exposed (>median) to lead with a specificity of 74 and 73% for patella and tibia lead levels, respectively, with 70% sensitivity. INTERPRETATION: DNA methylation-based lead biomarkers are novel tools that can be used to reconstruct decades' worth of individual cumulative lead exposure using only blood DNA methylation profiles and may help identify the consequences of cumulative exposure.


Assuntos
Metilação de DNA , Chumbo , Adulto , Idoso , Envelhecimento , Exposição Ambiental/efeitos adversos , Humanos , Chumbo/análise , Masculino , Patela/química , Patela/metabolismo , Tíbia/química , Tíbia/metabolismo
20.
J Clin Med ; 9(10)2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33086558

RESUMO

The global SARS-CoV-2 outbreak and subsequent lockdown had a significant impact on people's daily lives, with strong implications for stress levels due to the threat of contagion and restrictions to freedom. Given the link between high stress levels and adverse physical and mental consequences, the COVID-19 pandemic is certainly a global public health issue. In the present study, we assessed the effect of the pandemic on stress levels in N = 2053 Italian adults, and characterized more vulnerable individuals on the basis of sociodemographic features and stable psychological traits. A set of 18 psycho-social variables, generalized regressions, and predictive machine learning approaches were leveraged. We identified higher levels of perceived stress in the study sample relative to Italian normative values. Higher levels of distress were found in women, participants with lower income, and participants living with others. Higher rates of emotional stability and self-control, as well as a positive coping style and internal locus of control, emerged as protective factors. Predictive learning models identified participants with high perceived stress, with a sensitivity greater than 76%. The results suggest a characterization of people who are more vulnerable to experiencing high levels of stress during the COVID-19 pandemic. This characterization may contribute to early and targeted intervention strategies.

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