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1.
J Am Coll Cardiol ; 74(10): 1329-1331, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31488270
2.
Epigenetics ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31506003

RESUMO

DNA methylation (DNAm) has a well-established association with age in many tissues, including peripheral blood mononuclear cells (PBMCs). Compared to DNAm, the closely related epigenetic modification known as DNA hydroxymethylation (DNAhm) was much more recently discovered in mammals. Preliminary investigations have observed a positive correlation between gene body DNAhm and cis-gene expression. While some of these studies have observed an association between age and global DNAhm, none have investigated region-specific age-related DNAhm in human blood samples. In this study, we investigated DNAhm and gene expression in PBMCs of 10 young and 10 old, healthy female volunteers. Thousands of regions were differentially hydroxymethylated in the old vs. young individuals in gene bodies, exonic regions, enhancers, and promoters. Consistent with previous work, we observed directional consistency between age-related differences in DNAhm and gene expression. Further, age-related DNAhm and genes with high levels of DNAhm were enriched for immune system processes which may support a role of age-related DNAhm in immunosenescence.

3.
Epigenomics ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31509016

RESUMO

Aim: We investigated associations of prenatal socioeconomic status (SES) with DNA methylation at birth, and to explore persistence of associations into early (∼3 years) and mid-childhood (∼7 years) among 609 mother-child pairs in a Boston-area prebirth cohort. Materials & methods: First, we created a prenatal SES index comprising individual- and neighborhood-level metrics and examined associations of low (lowest 10%) versus high (upper 90%) SES with genome-wide DNA methylation in cord blood via the Infinium HumanMethylation450 BeadChip. Next, we evaluated persistence of associations detected in cord blood with DNA methylation of the same CpG sites measured in peripheral leukocytes in early- and mid-childhood. Results & conclusion: Low prenatal SES was associated with methylation at CpG sites near ACSF3, TNRC6C-AS1, MTMR4 and LRRN4. The relationship with LRRN4 persisted into early childhood.

4.
Am J Public Health ; 109(9): 1188, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31390254
5.
Aging (Albany NY) ; 11(16): 5895-5923, 2019 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-31422385

RESUMO

Telomere length (TL) is associated with several aging-related diseases. Here, we present a DNA methylation estimator of TL (DNAmTL) based on 140 CpGs. Leukocyte DNAmTL is applicable across the entire age spectrum and is more strongly associated with age than measured leukocyte TL (LTL) (r ~-0.75 for DNAmTL versus r ~ -0.35 for LTL). Leukocyte DNAmTL outperforms LTL in predicting: i) time-to-death (p=2.5E-20), ii) time-to-coronary heart disease (p=6.6E-5), iii) time-to-congestive heart failure (p=3.5E-6), and iv) association with smoking history (p=1.21E-17). These associations are further validated in large scale methylation data (n=10k samples) from the Framingham Heart Study, Women's Health Initiative, Jackson Heart Study, InChianti, Lothian Birth Cohorts, Twins UK, and Bogalusa Heart Study. Leukocyte DNAmTL is also associated with measures of physical fitness/functioning (p=0.029), age-at-menopause (p=0.039), dietary variables (omega 3, fish, vegetable intake), educational attainment (p=3.3E-8) and income (p=3.1E-5). Experiments in cultured somatic cells show that DNAmTL dynamics reflect in part cell replication rather than TL per se. DNAmTL is not only an epigenetic biomarker of replicative history of cells, but a useful marker of age-related pathologies that are associated with it.

6.
Environ Res ; 177: 108573, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31323394

RESUMO

Environmental pollution is an important modifiable determinant for preventing cardiovascular diseases. Acute exposure to air pollution is linked to severe adverse cardiovascular events, including venous thromboembolism risk. The adverse health effects seem to arise from blood-borne metals and transition metal components from exposure to particulate matter that, when breathed, passes through the lungs into the heart and the blood stream. Pollution affects health via mechanisms including oxidative stress and inflammation, and metals may have a detrimental effect on both the blood cells, particularly platelets, and circulation. Some evidences demonstrates atherotrombotic consequences of acute and chronic exposure to air pollution, but few studies have examined exposure effects on the prothrombotic biomarkers leading to venous thromboembolism. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, we performed a systematic review (14 papers) of the past twelve years, focusing on the relationship between inhalable airborne metal exposures and coagulative biomarker disorders leading to lower limb venous thromboembolisms, e.g., deep vein thrombosis. Results support the hypothesis that exposure to inhalable metals, as elemental compounds in particulate matter, cause changes or activation of a number of human prothrombotic hemostatic biomarkers.

7.
Nat Commun ; 10(1): 3095, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300640

RESUMO

The nasal cellular epigenome may serve as biomarker of airway disease and environmental response. Here we collect nasal swabs from the anterior nares of 547 children (mean-age 12.9 y), and measure DNA methylation (DNAm) with the Infinium MethylationEPIC BeadChip. We perform nasal Epigenome-Wide Association analyses (EWAS) of current asthma, allergen sensitization, allergic rhinitis, fractional exhaled nitric oxide (FeNO) and lung function. We find multiple differentially methylated CpGs (FDR < 0.05) and Regions (DMRs; ≥ 5-CpGs and FDR < 0.05) for asthma (285-CpGs), FeNO (8,372-CpGs; 191-DMRs), total IgE (3-CpGs; 3-DMRs), environment IgE (17-CpGs; 4-DMRs), allergic asthma (1,235-CpGs; 7-DMRs) and bronchodilator response (130-CpGs). Discovered DMRs annotated to genes implicated in allergic asthma, Th2 activation and eosinophilia (EPX, IL4, IL13) and genes previously associated with asthma and IgE in EWAS of blood (ACOT7, SLC25A25). Asthma, IgE and FeNO were associated with nasal epigenetic age acceleration. The nasal epigenome is a sensitive biomarker of asthma, allergy and airway inflammation.

8.
Environ Int ; 131: 105018, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31336254

RESUMO

BACKGROUND: Whole-body and thoracic ionizing radiation exposure are both associated with the development of renal dysfunction. However, whether low-level environmental radiation from air pollution affects renal function remains unknown. OBJECTIVES: We investigated the association of particle radioactivity (PR) with renal function defined by the estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD) in the Normative Aging Study. METHODS: This longitudinal analysis included 2491 medical visits from 809 white males enrolled between 1999 and 2013. The eGFR was calculated using the CKD-EPI and MDRD equations, and CKD cases were identified as those with an eGFR <60 mL/min/1.73 m2. Gross ß activity measured by five monitors of the U.S. Environmental Protection Agency's RadNet monitoring network was utilized to represent PR. RESULTS: Ambient PR levels from 1 to 28 days prior to clinical visit demonstrated robust negative associations with both forms of eGFR, but not with the increased odds of CKD. An interquartile range higher 28-day average ambient PR level was significantly associated with 0.83-mL/min/1.73 m2 lower eGFR estimated by the CKD-EPI equation (95% confidence interval: -1.46, -0.20, p-value = 0.01). Controlling for PM2.5 or black carbon in the model slightly attenuated the PR effects on eGFR. However, in individuals with the highest levels (3rd tertile) of C-reactive protein (CRP) or fibrinogen, we observed robust associations of PR with eGFR and CKD, suggesting that systemic inflammation may modify the PR-eGFR and PR-CKD relationships. CONCLUSIONS: Our study reveals adverse health effects of short-term low-level ambient PR on the renal function, providing evidence to guide further study of the interplay between PR, inflammation, and renal health.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31315170

RESUMO

Essential hypertension is the leading preventable cause of death in the world. Epidemiological studies have shown that physical training can reduce blood pressure (BP), both in hypertensive and healthy individuals. Increasing evidence is emerging that DNA methylation is involved in alteration of the phenotype and of vascular function in response to environmental stimuli. We evaluated repetitive element and gene-specific DNA methylation in peripheral blood leukocytes of 68 volunteers, taken before (T0) and after (T1) a three-month intervention protocol of continuative aerobic physical exercise. DNA methylation was assessed by bisulfite-PCR and pyrosequencing. Comparing T0 and T1 measurements, we found an increase in oxygen consumption at peak of exercise (VO2peak) and a decrease in diastolic BP at rest. Exercise increased the levels of ALU and Long Interspersed Nuclear Element 1 (LINE-1) repetitive elements methylation, and of Endothelin-1 (EDN1), Inducible Nitric Oxide Synthase (NOS2), and Tumour Necrosis Factor Alpha (TNF) gene-specific methylation. VO2peak was positively associated with methylation of ALU, EDN1, NOS2, and TNF; systolic BP at rest was inversely associated with LINE-1, EDN1, and NOS2 methylation; diastolic BP was inversely associated with EDN1 and NOS2 methylation. Our findings suggest a possible role of DNA methylation for lowering systemic BP induced by the continuative aerobic physical training program.

10.
Aging (Albany NY) ; 11(14): 4970-4989, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31322503

RESUMO

Evidence indicates associations between higher optimism and reduced risk of age-related conditions and premature mortality. This suggests optimism is a positive health asset, but research identifying potential biological mechanisms underlying these associations remains limited. One potential pathway is slower cellular aging, which may delay age-related deterioration in health. Data were from the Women's Health Initiative (WHI) (N=3,298) and the Veterans Affairs Normative Aging Study (NAS) (N=514), and included dispositional and explanatory style optimism measures. We evaluated whether higher optimism was associated with metrics suggestive of less cellular aging, as indicated by two DNA methylation algorithms, intrinsic (IEAA) and extrinsic epigenetic age acceleration (EEAA); these algorithms represent accelerated biologic aging that exceeds chronological age. We used linear regression models to test our hypothesis while considering several covariates (sociodemographics, depressive symptoms, health behaviors). In both cohorts, we found consistently null associations of all measures of optimism with both measures of DNA methylation aging, regardless of covariates considered. For example, in fully-adjusted models, dispositional optimism was not associated with either IEAA (WHI:ß=0.02; 95% Confidence Interval [CI]:-0.15-0.20; NAS:ß=-0.06; 95% CI:-0.56-0.44) or EEAA (WHI:ß=-0.04; 95% CI: -0.26-0.17; NAS:ß=-0.17; 95% CI: -0.80-0.46). Higher optimism was not associated with reduced cellular aging as measured in this study.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31277270

RESUMO

DNA methylation may play a critical role in aging and age-related diseases. DNA methylation phenotypic age (DNAmPhenoAge) is a new aging biomarker and predictor of chronic disease risk. While smoking is a strong risk factor for chronic diseases and influences methylation, its influence on DNAmPhenoAge is unknown. We investigated associations of self-reported and epigenetic smoking indicators with DNAmPhenoAge acceleration in a longitudinal aging study in eastern Massachusetts. DNA methylation was measured in whole blood samples from multiple visits for 692 male participants in the Veterans Affairs Normative Aging Study during 1999-2013. Acceleration was defined using residuals from linear regression of the DNAmPhenoAge on the chronological age. Cumulative smoking (pack-years) was significantly associated with DNAmPhenoAge acceleration, whereas self-reported smoking status was not. We observed significant validated associations between smoking-related loci and DNAmPhenoAge acceleration for 52 CpG sites, where 18 were hypomethylated and 34 were hypermethylated, mapped to 16 genes. The AHRR gene had the most loci (N = 8) among the 16 genes. We generated a smoking aging index based on these 52 loci, which showed positive significant associations with DNAmPhenoAge acceleration. These epigenetic biomarkers may help to predict age-related risks driven by smoking.

12.
Fertil Steril ; 112(2): 387-396.e3, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31146888

RESUMO

OBJECTIVE: To study whether increased body mass index is associated with altered expression of extracellular vesicle microRNAs (EV-linked miRNAs) in human follicular fluid. DESIGN: Cross-sectional study. SETTING: Tertiary-care university-affiliated center. PATIENT(S): One hundred thirty-three women undergoing in vitro fertilization (IVF) were recruited from January 2014 to August 2016. INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): EV-linked miRNAs were isolated from follicular fluid and their expression profiles were measured with the use of the Taqman Open Array Human miRNA panel. EV-linked miRNAs were globally normalized and inverse-normal transformed. Associations between body mass index (BMI) and EV-linked miRNA outcomes were analyzed by means of multivariate linear regression and principal component analysis. RESULT(S): Eighteen EV-linked miRNAs were associated with an increase in BMI after adjusting for age, ethnicity, smoking status, and batch effects. Hsa-miR-328 remained significant after false discovery rate adjustments. Principal component analyses identified the first principal component to account for 40% of the variation in our EV-linked miRNA dataset, and adjusted linear regression found that the first principal component was significantly associated with BMI after multiple testing adjustments. Using Kyoto Encyclopedia of Genes and Genomes enrichment analyses, we predicted gene targets of EV-linked miRNA in silico and identified PI3K-Akt signaling, ECM-receptor interaction, focal adhesion, FoxO signaling, and oocyte meiosis pathways. CONCLUSION(S): These results show that a 1-unit increase in BMI is associated with altered follicular fluid expression of EV-linked miRNAs that may influence follicular and oocyte developmental pathways. Our findings provide potential insight into a mechanistic explanation for the reduced fertility rates associated with increased BMI.

13.
Hypertension ; 74(2): 375-383, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31230546

RESUMO

Hypertensive disorders of pregnancy (HDP) are associated with low birth weight, shorter gestational age, and increased risk of maternal and offspring cardiovascular diseases later in life. The mechanisms involved are poorly understood, but epigenetic regulation of gene expression may play a part. We performed meta-analyses in the Pregnancy and Childhood Epigenetics Consortium to test the association between either maternal HDP (10 cohorts; n=5242 [cases=476]) or preeclampsia (3 cohorts; n=2219 [cases=135]) and epigenome-wide DNA methylation in cord blood using the Illumina HumanMethylation450 BeadChip. In models adjusted for confounders, and with Bonferroni correction, HDP and preeclampsia were associated with DNA methylation at 43 and 26 CpG sites, respectively. HDP was associated with higher methylation at 27 (63%) of the 43 sites, and across all 43 sites, the mean absolute difference in methylation was between 0.6% and 2.6%. Epigenome-wide associations of HDP with offspring DNA methylation were modestly consistent with the equivalent epigenome-wide associations of preeclampsia with offspring DNA methylation (R2=0.26). In longitudinal analyses conducted in 1 study (n=108 HDP cases; 550 controls), there were similar changes in DNA methylation in offspring of those with and without HDP up to adolescence. Pathway analysis suggested that genes located at/near HDP-associated sites may be involved in developmental, embryogenesis, or neurological pathways. HDP is associated with offspring DNA methylation with potential relevance to development.

14.
Nat Commun ; 10(1): 2581, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31197173

RESUMO

Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of its functional relevance remains limited. Here we show the effect of differential methylation in the early phases of T2D pathology by a blood-based epigenome-wide association study of 4808 non-diabetic Europeans in the discovery phase and 11,750 individuals in the replication. We identify CpGs in LETM1, RBM20, IRS2, MAN2A2 and the 1q25.3 region associated with fasting insulin, and in FCRL6, SLAMF1, APOBEC3H and the 15q26.1 region with fasting glucose. In silico cross-omics analyses highlight the role of differential methylation in the crosstalk between the adaptive immune system and glucose homeostasis. The differential methylation explains at least 16.9% of the association between obesity and insulin. Our study sheds light on the biological interactions between genetic variants driving differential methylation and gene expression in the early pathogenesis of T2D.


Assuntos
Metilação de DNA/fisiologia , Diabetes Mellitus Tipo 2/genética , Glucose/metabolismo , Insulina/metabolismo , Obesidade/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Simulação por Computador , Ilhas de CpG/genética , Diabetes Mellitus Tipo 2/metabolismo , Epigênese Genética/fisiologia , Epigenômica/métodos , Feminino , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica/genética , Estudo de Associação Genômica Ampla/métodos , Homeostase/genética , Humanos , Masculino , Redes e Vias Metabólicas/genética , Pessoa de Meia-Idade , Obesidade/metabolismo , Polimorfismo de Nucleotídeo Único/fisiologia , Adulto Jovem
15.
Environ Int ; : 104723, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31208937

RESUMO

BACKGROUND: DNA methylation (DNAm) may contribute to processes that underlie associations between air pollution and poor health. Therefore, our objective was to evaluate associations between DNAm and ambient concentrations of particulate matter (PM) ≤2.5, ≤10, and 2.5-10 µm in diameter (PM2.5; PM10; PM2.5-10). METHODS: We conducted a methylome-wide association study among twelve cohort- and race/ethnicity-stratified subpopulations from the Women's Health Initiative and the Atherosclerosis Risk in Communities study (n = 8397; mean age: 61.5 years; 83% female; 45% African American; 9% Hispanic/Latino American). We averaged geocoded address-specific estimates of daily and monthly mean PM concentrations over 2, 7, 28, and 365 days and 1 and 12 months before exams at which we measured leukocyte DNAm in whole blood. We estimated subpopulation-specific, DNAm-PM associations at approximately 485,000 Cytosine-phosphate-Guanine (CpG) sites in multi-level, linear, mixed-effects models. We combined subpopulation- and site-specific estimates in fixed-effects, inverse variance-weighted meta-analyses, then for associations that exceeded methylome-wide significance and were not heterogeneous across subpopulations (P < 1.0 × 10-7; PCochran's Q > 0.10), we characterized associations using publicly accessible genomic databases and attempted replication in the Cooperative Health Research in the Region of Augsburg (KORA) study. RESULTS: Analyses identified significant DNAm-PM associations at three CpG sites. Twenty-eight-day mean PM10 was positively associated with DNAm at cg19004594 (chromosome 20; MATN4; P = 3.33 × 10-8). One-month mean PM10 and PM2.5-10 were positively associated with DNAm at cg24102420 (chromosome 10; ARPP21; P = 5.84 × 10-8) and inversely associated with DNAm at cg12124767 (chromosome 7; CFTR; P = 9.86 × 10-8). The PM-sensitive CpG sites mapped to neurological, pulmonary, endocrine, and cardiovascular disease-related genes, but DNAm at those sites was not associated with gene expression in blood cells and did not replicate in KORA. CONCLUSIONS: Ambient PM concentrations were associated with DNAm at genomic regions potentially related to poor health among racially, ethnically and environmentally diverse populations of U.S. women and men. Further investigation is warranted to uncover mechanisms through which PM-induced epigenomic changes may cause disease.

16.
Int J Hyg Environ Health ; 222(5): 756-764, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31103472

RESUMO

BACKGROUND: Ambient particulate air pollution is a major threat to the cardiovascular health of people. Inflammation is an important component of the pathophysiological process that links air pollution and cardiovascular disease (CVD). A classical marker of inflammation-C-reactive protein (CRP), has been recognized as an independent predictor of CVD risk. Exposure to ambient particulate matter (PM) may cause systemic inflammatory response but its association with CRP has been inconsistently reported. OBJECTIVES: To estimate the potential effects of short-term and long-term exposures to ambient particulate air pollution on circulating CRP level based on previous epidemiological studies. METHODS: A systematic literature search of PubMed, Web of Science, Embase, and Scopus databases for publications up to January 2018 was conducted for studies reporting the association between ambient PM (PM2.5 or PM10, or both) and circulating CRP level. We performed a meta-analysis for the associations reported in individual studies using a random-effect model and evaluated the effect modification by major potential modifiers. RESULTS: This meta-analysis comprised data from 40 observational studies conducted on 244,681 participants. These included 32 (27 PM2.5 studies and 13 PM10 studies) and 11 (9 PM2.5 studies and 5 PM10 studies) studies that investigated the associations of CRP with short-term and long-term exposure to particulate air pollution, respectively. A 10 µg/m3 increase in short-term exposure to PM2.5 and PM10 was associated with increases of 0.83 % (95% CI: 0.30%, 1.37%) and 0.39% (95% CI: -0.04%, 0.82%) in CRP level, respectively, and a 10 µg/m3 increase in long-term exposure to PM2.5 and PM10 was associated with much higher increases of 18.01% (95% CI: 5.96%, 30.06%) and 5.61% (95% CI: 0.79%, 10.44%) in CRP level, respectively. The long-term exposure to particulate air pollution was more strongly associated with CRP level than short-term exposure and PM2.5 had a greater effect on CRP level than PM10. CONCLUSION: Exposure to ambient particulate air pollution is associated with elevated circulating CRP level suggesting an activated systemic inflammatory state upon exposure, which may explain the association between particulate air pollution and CVD risk.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31058973

RESUMO

CONTEXT: Underlying mechanisms leading to Gestational Diabetes Mellitus (GDM) are still under investigation and it is unclear whether the placenta plays a role in triggering glucose intolerance or if its functions are modified in response to the hyperglycemia. Circulating microRNAs are involved in placental development and function and are encapsulated in Extracellular Vesicles (EVs). OBJECTIVE: to compare differential expression of microRNAs in circulating EVs in pregnancies complicated by GDM versus controls. METHODS: a case-control study nested in a prospective pregnancy cohort including 23 women with GDM and 46 matched controls. The presence of serum EVs in early pregnancy was validated by transmission electron microscopy. Placental dimensions were assessed at 11-13 weeks of gestation. Differential expression of seventeen EV-miRNAs (miR-122-5p; -132-3p; -1323; -182-3p; -210-3p; -29a-3p; -29b-3p; -342-3p; -517-5p; -517a-3p; -518b; -520h; -525-5p; -136-5p; -342-3p; -376c-5p and -494-3p) was assessed using reverse transcription quantitative polymerase chain reaction. RESULTS: EVs were present in the early phase of placentation (6-15 weeks of gestation) in both cases and controls. No difference was observed for placental dimensions and estimated placental volume between GDM and control groups.10 miRNAs (miR-122-5p; -132-3p; -1323; -136-5p; -182-3p; -210-3p; -29a-3p; -29b-3p; -342-3p and -520h) showed significantly higher levels in GDM cases compared to controls (p≤0.05). Bioinformatics analysis showed that these miRNAs are involved in trophoblast proliferation/differentiation, as well as in insulin secretion/regulation and glucose transport in pregnant women. CONCLUSION: The miRNA content of blood EVs may be a promising avenue for studying the early impact of impaired glucose metabolism on placental development.

19.
Ann Epidemiol ; 35: 48-52.e2, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31060895

RESUMO

PURPOSE: Cognitive development during adolescence affects health long term. We investigated whether level of and change in language-based cognition during adolescence are associated with cognitive performance in midlife. METHODS: Participants were enrolled in the Child Health and Development Study and followed during midlife (47-52 years). Adolescent cognition was measured with the Peabody Picture Vocabulary Test at ages 9-11 years (PPVT-9) and 15-17 years (PPVT-15). We examined PPVT-9, as well as a PPVT change score (derived using the standardized regression-based method) in relation to midlife cognition measures of Wechsler Test of Adult Reading, Verbal Fluency, and Digit Symbol tests. Linear regression models were adjusted for childhood socioeconomic status, age, sex, race, and midlife marital status, education, and occupational score. RESULTS: In 357 participants (52.1% female, 25.6% African American), both PPVT-9 (ß [95% confidence interval [CI] = 0.26 [0.18, 0.34]) and PPVT change score (ß [95% CI] = 2.03 [1.27, 2.80]) were associated with Wechsler Test of Adult Reading at midlife. PPVT-9 was associated with midlife Verbal Fluency (ß [95% CI] = 0.18 [0.10, 0.25]), whereas PPVT change score was not (ß [95% CI] = -0.01 [-0.68, 0.67]). Neither PPVT-9 nor PPVT change score was associated with midlife Digit Symbol. CONCLUSIONS: Both level of and change in language-based cognition during adolescence were associated with midlife vocabulary and language function, even after controlling for midlife occupation and education.

20.
J Perinatol ; 39(7): 941-948, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31110244

RESUMO

OBJECTIVE: To determine whether prenatal sex hormones from maternal saliva are associated with birth-weight-for-gestational age. STUDY DESIGN: We measured salivary progesterone, testosterone, estradiol, dehydroepiandrosterone (DHEA), and cortisone in 504 pregnant women in a Mexico City cohort. We performed linear and modified Poisson regression to examine associations of log-transformed hormones with birth-weight-for-gestational age z-scores and the risk of small-for-gestational age (SGA) and large-for-gestational age (LGA) adjusting for maternal age, sex, BMI, parity, smoking, education, and socioeconomic status. RESULTS: In total, 15% of infants were SGA and 2% were LGA. Each interquartile range increment in testosterone/estradiol ratio was associated with a 0.12 decrement in birth-weight-for-gestational age z-score (95% CI: -0.27 to -0.02) and a 50% higher risk of SGA versus appropriate-for-gestational age (AGA) (95% CI: 1.13-1.99). CONCLUSION: Higher salivary testosterone/estradiol ratios may affect fetal growth, and identifying the predictors of hormone levels may be important to optimizing fetal growth.

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