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1.
Psychosom Med ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39132939

RESUMO

OBJECTIVES: We aimed to investigate the prevalence of sleep disturbances and associated factors among Ukrainians one year after Russia's full-scale invasion. METHODS: Quota sampling was used to collect online survey data from 2,364 adults living in Ukraine aged 18-79 years from 5 April 2023 to 15 May 2023. Short sleep duration was defined as sleep duration ≤6 hours and long sleep duration as ≥9 hours. Insomnia was assessed by the Insomnia Symptom Questionnaire. RESULTS: The prevalence of short sleep duration, long sleep duration, and insomnia was 39.4%, 6.9%, and 38.5%, respectively. Short sleep duration and insomnia were both more likely in females (short sleep duration adjusted odds ratio (aOR) = 1.44; insomnia: aOR = 2.17), individuals with depression (short sleep duration: aOR = 1.61; insomnia: aOR = 7.76), affected by the 2014 Russian invasion (short sleep duration: aOR = 1.37; insomnia: aOR = 1.78), and with more trauma events (short sleep duration: Quartile 3 vs Q1: aOR = 1.88; Q4 vs Q1: aOR = 1.83; insomnia: Q3 vs Q1: aOR = 2.14; Q4 vs Q1: aOR = 2.32). Insomnia was more likely in Ukrainians with PTSD (aOR = 2.95), anxiety (aOR = 4.57), and loneliness (aOR = 1.67). Essential public service was associated with short sleep duration (aOR = 1.64). Short sleep duration and insomnia were associated with lower quality of life in physical, psychological, and environmental domains. Insomnia was associated with the social relationships domain. CONCLUSIONS: Sleep health among Ukrainian adults one year into the war is concerning, with more than one-third reporting inadequate sleep or insomnia. More studies are needed on impacts and interventions for sleep health during and after the war.

2.
J Nutr Metab ; 2024: 6611169, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39015539

RESUMO

Poor sleep quality and psychological distress in pregnancy are important health concerns. Serotonin and melatonin levels may underlie variation in these adverse outcomes. In this study, we examined dietary nutrients involved in serotonin and melatonin synthesis in relation to maternal sleep quality and affective symptoms during pregnancy. Pregnant women at no greater than normal medical risk at enrollment completed 24-hour dietary recalls in mid-late pregnancy. Usual intakes of vitamin B6, vitamin D, eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA), and tryptophan were estimated from dietary intake of foods and supplements using the National Cancer Institute (NCI) method. Sleep quality, depression, and anxiety were measured using validated questionnaires. Associations between nutrient intakes, sleep quality, and affective symptoms were estimated using generalized estimating equation models adjusting for potential confounding factors. In minimally adjusted models, EPA + DHA and tryptophan intakes were associated with a lower score indicating better sleep quality (b: -1.07, 95% CI: -2.09, -0.05) and (b: -12.40, 95% CI: -24.60, -0.21), respectively. EPA + DHA and tryptophan intakes were also associated with a lower odds of shorter sleep duration and sleep disturbances. In addition, tryptophan was associated with a lower odds of higher sleep latency. However, associations were attenuated and nonsignificant after adjustment for demographic and lifestyle factors. In conclusion, intakes of EPA + DHA and tryptophan were associated with improved sleep quality, but these associations were confounded by maternal demographic and lifestyle characteristics. This study highlights the need to consider dietary intake and pregnancy health in the context of demographic characteristics and lifestyle behaviors.

3.
PLoS One ; 19(7): e0305004, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38959439

RESUMO

OBJECTIVE: Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse birth and developmental outcomes in children. We aimed to describe prenatal PAH exposures in a large, multisite U.S. consortium. METHODS: We measured 12 mono-hydroxylated metabolites (OH-PAHs) of 7 PAHs (naphthalene, fluorene, phenanthrene, pyrene, benzo(c)phenanthrene, chrysene, benz(a)anthracene) in mid-pregnancy urine of 1,892 pregnant individuals from the ECHO PATHWAYS consortium cohorts: CANDLE (n = 988; Memphis), TIDES (n = 664; Minneapolis, Rochester, San Francisco, Seattle) and GAPPS (n = 240; Seattle and Yakima, WA). We described concentrations of 8 OH-PAHs of non-smoking participants (n = 1,695) by site, socioeconomic characteristics, and pregnancy stage (we report intraclass correlation coefficients (ICC) for n = 677 TIDES participants). RESULTS: Exposure to the selected PAHs was ubiquitous at all sites. 2-hydroxynaphthalene had the highest average concentrations at all sites. CANDLE had the highest average concentrations of most metabolites. Among non-smoking participants, we observed some patterns by income, education, and race but these were not consistent and varied by site and metabolite. ICCs of repeated OH-PAH measures from TIDES participants were ≤ 0.51. CONCLUSION: In this geographically-diverse descriptive analysis of U.S. pregnancies, we observed ubiquitous exposure to low molecular weight PAHs, highlighting the importance of better understanding PAH sources and their pediatric health outcomes attributed to early life PAH exposure.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Humanos , Feminino , Gravidez , Hidrocarbonetos Policíclicos Aromáticos/urina , Estados Unidos , Adulto , Estudos de Coortes , Exposição Materna/efeitos adversos , Adulto Jovem
4.
medRxiv ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-39040193

RESUMO

Long-standing hypertension (HTN) affects multiple organ systems and leads to pathologic arterial remodeling, which is driven largely by smooth muscle cell (SMC) plasticity. Although genome wide association studies (GWAS) have identified numerous variants associated with changes in blood pressure in humans, only a small percentage of these variants actually cause HTN. In order to identify relevant genes important in SMC function in HTN, we screened three separate human GWAS and Mendelian randomization studies to identify SNPs located within non-coding gene regions, focusing on genes encoding epigenetic enzymes, as these have been recently identified to control SMC fate in cardiovascular disease. We identified SNPs rs62059712 and rs74480102 in the promoter of the human JMJD3 gene and show that the minor C allele increases JMJD3 transcription in SMCs via increased SP1 binding to the JMJD3 promoter. Using our novel SMC-specific Jmjd3-deficient murine model ( Jmjd3 flox/flox Myh11 CreERT ), we show that loss of Jmjd3 in SMCs results in HTN, mechanistically, due to decreased EDNRB expression and a compensatory increase in EDNRA expression. As a translational corollary, through single cell RNA-sequencing (scRNA-seq) of human arteries, we found strong correlation between JMJD3 and EDNRB expression in SMCs. Further, we identified that JMJD3 is required for SMC-specific gene expression, and loss of JMJD3 in SMCs in the setting of HTN results in increased arterial remodeling by promoting the SMC synthetic phenotype. Our findings link a HTN-associated human DNA variant with regulation of SMC plasticity, revealing therapeutic targets that may be used in the screening and/or personalized treatment of HTN.

5.
Psychiatry Res ; 339: 116056, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38968918

RESUMO

We aimed to assess the mental health of adults living in Ukraine one year after onset of the Russo-Ukrainian war, along with quality of life and coping strategies. Quota sampling was used to collect online survey data from 2364 adults aged 18-79 years living in Ukraine from April 5, 2023 to May 15, 2023. Among adults living in Ukraine, 14.4 % had probable post-traumatic stress disorder (PTSD), another 8.9 % had complex PTSD (CPTSD), 44.2 % had probable depressive disorder, 23.1 % had anxiety disorder and 38.6 % showed significant loneliness. In adjusted models, the number of trauma events experienced during the war showed a dose-response association with PTSD/CPTSD and was associated with depressive disorder and anxiety disorder. Quality of life domains, particularly physical quality of life, were negatively associated with PTSD/CPTSD, depressive disorder, anxiety disorder, and number of trauma events. Maladaptive coping was positively associated with depressive disorder, anxiety disorder, PTSD/CPTSD and loneliness. All quality of life domains were positively associated with using adaptive coping strategies. Mental health disorders are highly prevalent in adults living in Ukraine one year into the war. Policy and services can promote adaptive coping strategies to improve mental health and quality of life for increased resilience during war.


Assuntos
Adaptação Psicológica , Qualidade de Vida , Transtornos de Estresse Pós-Traumáticos , Humanos , Adulto , Pessoa de Meia-Idade , Qualidade de Vida/psicologia , Masculino , Ucrânia/epidemiologia , Feminino , Estudos Transversais , Idoso , Adulto Jovem , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Adaptação Psicológica/fisiologia , Adolescente , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/psicologia , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/psicologia , Saúde Mental , Federação Russa/epidemiologia , Solidão/psicologia
6.
Curr Environ Health Rep ; 11(3): 390-403, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38985433

RESUMO

PURPOSE OF REVIEW: Environmental chemical exposures may disrupt child development, with long-lasting health impacts. To date, U.S. studies of early environmental exposures have been limited in size and diversity, hindering power and generalizability. With harmonized data from over 60,000 participants representing 69 pregnancy cohorts, the National Institutes of Health's Environmental influences on Child Health Outcomes (ECHO) Program is the largest study of U.S. children's health. Here, we: (1) review ECHO-wide studies of chemical exposures and maternal-child health; and (2) outline opportunities for future research using ECHO data. RECENT FINDINGS: As of early 2024, in addition to over 200 single-cohort (or award) papers on chemical exposures supported by ECHO, ten collaborative multi-cohort papers have been made possible by ECHO data harmonization and new data collection. Multi-cohort papers have examined prenatal exposure to per- and polyfluoroalkyl substances (PFAS), phthalates, phenols and parabens, organophosphate esters (OPEs), metals, melamine and aromatic amines, and emerging contaminants. They have primarily focused on describing patterns of maternal exposure or examining associations with maternal and infant outcomes; fewer studies have examined later child outcomes (e.g., autism) although follow up of enrolled ECHO children continues. The NICHD's Data and Specimen Hub (DASH) database houses extensive ECHO data including over 470,000 chemical assay results and complementary data on priority outcome areas (pre, peri-, and postnatal, airway, obesity, neurodevelopment, and positive health), making it a rich resource for future analyses. ECHO's extensive data repository, including biomarkers of chemical exposures, can be used to advance our understanding of environmental influences on children's health. Although few published studies have capitalized on these unique harmonized data to date, many analyses are underway with data now widely available.


Assuntos
Saúde da Criança , Exposição Ambiental , Humanos , Estados Unidos , Feminino , Gravidez , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Criança , Efeitos Tardios da Exposição Pré-Natal , Poluentes Ambientais/análise , Exposição Materna/efeitos adversos , Pré-Escolar , Desenvolvimento Infantil/efeitos dos fármacos , Lactente , Saúde Materna
7.
Curr Environ Health Rep ; 11(3): 356-379, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39037689

RESUMO

PURPOSE OF REVIEW: Many synthetic endocrine-disrupting chemicals (EDCs) are ubiquitous in the environment and highly detected among pregnant people. These chemicals may disrupt maternal and/or fetal sex steroid hormones, which are critical to pregnancy maintenance and fetal development. Here, we review the epidemiological literature examining prenatal exposure to common synthetic EDCs in relation to maternal and fetal sex steroid hormones. RECENT FINDINGS: We performed a literature search using PubMed, SCOPUS, and Embase, ultimately identifying 29 articles for full review. Phenols, parabens, and persistent organic pollutants generally showed inverse associations with androgens, estrogens, and progesterone. Phthalates and per-and polyfluoroalkyl substances tended to be inversely associated with progesterone, while evidence regarding androgens and estrogens was mixed. Inconsistent, but noteworthy, differences by fetal sex and timing of exposure/outcome were observed. Overall, the literature suggests EDCs may disrupt maternal and fetal sex steroid activity, though findings are mixed. Given the pervasive, high-volume production of these synthetic chemicals and the critical functions sex steroid hormones play during gestation, additional research is warranted.


Assuntos
Disruptores Endócrinos , Hormônios Esteroides Gonadais , Humanos , Gravidez , Feminino , Exposição Materna/efeitos adversos , Feto/efeitos dos fármacos , Poluentes Orgânicos Persistentes , Ácidos Ftálicos
8.
Am J Clin Nutr ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38960320

RESUMO

BACKGROUND: Prenatal fish intake is a key source of omega-3 (ω-3) polyunsaturated fatty acids needed for brain development, yet intake is generally low, and studies addressing associations with autism spectrum disorder (ASD) and related traits are lacking. OBJECTIVE: This study aimed to examine associations of prenatal fish intake and ω-3 supplement use with both autism diagnosis and broader autism-related traits. METHODS: Participants were drawn from 32 cohorts in the Environmental influences on Child Health Outcomes Cohort Consortium. Children were born between 1999 and 2019 and part of ongoing follow-up with data available for analysis by August 2022. Exposures included self-reported maternal fish intake and ω-3/fish oil supplement use during pregnancy. Outcome measures included parent report of clinician-diagnosed ASD and parent-reported autism-related traits measured by the Social Responsiveness Scale (SRS)-second edition (n = 3939 and v3609 for fish intake analyses, respectively; n = 4537 and n = 3925 for supplement intake analyses, respectively). RESULTS: In adjusted regression models, relative to no fish intake, fish intake during pregnancy was associated with reduced odds of autism diagnosis (odds ratio: 0.84; 95% confidence interval [CI]: 0.77, 0.92), and a modest reduction in raw total SRS scores (ß: -1.69; 95% CI: -3.3, -0.08). Estimates were similar across categories of fish consumption from "any" or "less than once per week" to "more than twice per week." For ω-3 supplement use, relative to no use, no significant associations with autism diagnosis were identified, whereas a modest relation with SRS score was suggested (ß: 1.98; 95% CI: 0.33, 3.64). CONCLUSIONS: These results extend previous work by suggesting that prenatal fish intake, but not ω-3 supplement use, may be associated with lower likelihood of both autism diagnosis and related traits. Given the low-fish intake in the United States general population and the rising autism prevalence, these findings suggest the need for better public health messaging regarding guidelines on fish intake for pregnant individuals.

9.
J Speech Lang Hear Res ; 67(7): 2077-2085, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38843437

RESUMO

OBJECTIVE: The pharyngeal swallow typically begins within 400 ms following the arrival of a liquid bolus in the pharynx. By contrast, processed food particles aggregate in the valleculae prior to swallow initiation. With solid foods, swallow reaction time (SRT), the interval between bolus passing the ramus of mandible and hyoid burst onset (HYB) can be subdivided into components of vallecular aggregation time (VAT) and the subsequent end of aggregation to hyoid burst interval (EOA-to-HYB). However, expected durations of these timing measures remain unclear. We aimed to study bolus aggregation in healthy swallowing for International Dysphagia Diet Standardisation Initiative Food Levels 5 (minced and moist [MM5]), 6 (soft and bite-sized [SB6]), and 7 (regular [RG7]). Understanding typical patterns and durations of vallecular aggregation with solids in healthy swallowing will inform the identification of impaired swallow timing in patient populations. DESIGN: Twenty healthy adults (10 males, Mage = 28 years, range: 23-55 years) swallowed two boluses each of MM5, SB6, and RG7 foods in videofluoroscopy. Blinded duplicate ratings determined bolus location at swallow onset, SRT, VAT, and EOA-to-HYB. Texture-based differences were measured using Friedman's tests. Bolus location was at/above the valleculae at swallow onset for 85% of boluses, with no differences by texture. SRT, VAT, and EOA-to-HYB did not vary by texture, with overall median values (interquartile range) of 99 ms (-66 to 743 ms) for SRT, 347 ms (66 to 891 ms) for VAT, and -132 ms (-231 to -83 ms) for EOA-to-HYB. CONCLUSIONS: These data corroborate prior evidence that it is not unusual for food particles to aggregate in the valleculae prior to swallow initiation in healthy swallowing. However, durations of vallecular aggregation are typically < 1 s in healthy adults.


Assuntos
Deglutição , Alimentos , Humanos , Deglutição/fisiologia , Masculino , Adulto , Pessoa de Meia-Idade , Feminino , Adulto Jovem , Voluntários Saudáveis , Tempo de Reação , Faringe/fisiologia , Transtornos de Deglutição/fisiopatologia , Osso Hioide/fisiologia , Osso Hioide/diagnóstico por imagem
10.
Int J Hyg Environ Health ; 260: 114407, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38879913

RESUMO

BACKGROUND: Executive functions develop rapidly in childhood, enabling problem-solving, focused attention, and planning. Exposures to environmental toxicants in pregnancy may impair healthy executive function development in children. There is increasing concern regarding polycyclic aromatic hydrocarbons (PAHs) given their ability to transfer across the placenta and the fetal blood-brain barrier, yet evidence from epidemiological studies is limited. METHODS: We examined associations between prenatal PAH exposure and executive functions in 814 children of non-smoking mothers from two U.S. cohorts in the ECHO-PATHWAYS Consortium. Seven mono-hydroxylated PAH metabolites were measured in mid-pregnancy urine and analyzed individually and as mixtures. Three executive function domains were measured at age 8-9: cognitive flexibility, working memory, and inhibitory control. A composite score quantifying overall performance was further calculated. We fitted linear regressions adjusted for socio-demographics, maternal health behaviors, and psychological measures, and examined modification by child sex and stressful life events in pregnancy. Bayesian kernel machine regression was performed to estimate the interactive and overall effects of the PAH mixture. RESULTS: The results from primary analysis of linear regressions were generally null, and no modification by child sex or maternal stress was indicated. Mixture analyses suggested several pairwise interactions between individual PAH metabolites in varied directions on working memory, particularly interactions between 2/3/9-FLUO and other PAH metabolites, but no overall or individual effects were evident. CONCLUSION: We conducted a novel exploration of PAH-executive functions association in a large, combined sample from two cohorts. Although findings were predominantly null, the study carries important implications for future research and contributes to evolving science regarding developmental origins of diseases.


Assuntos
Função Executiva , Hidrocarbonetos Policíclicos Aromáticos , Efeitos Tardios da Exposição Pré-Natal , Humanos , Feminino , Hidrocarbonetos Policíclicos Aromáticos/urina , Gravidez , Função Executiva/efeitos dos fármacos , Criança , Masculino , Estudos de Coortes , Poluentes Ambientais/urina , Adulto , Memória de Curto Prazo/efeitos dos fármacos , Exposição Materna
11.
Int J Hyg Environ Health ; 260: 114405, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38878407

RESUMO

Zearalenone (ZEN) is a fungal-derived toxin found in global food supplies including cereal grains and processed foods, impacting populations worldwide through diet. Because the chemical structure of ZEN and metabolites closely resembles 17ß-estradiol (E2), they interact with estrogen receptors α/ß earning their designation as 'mycoestrogens'. In animal models, gestational exposure to mycoestrogens disrupts estrogen activity and impairs fetal growth. Here, our objective was to evaluate relationships between mycoestrogen exposure and sex steroid hormone concentrations in maternal circulation and cord blood for the first time in humans. In each trimester, pregnant participants in the UPSIDE study (n = 297) provided urine for mycoestrogen analysis and serum for hormone analysis. At birth, placental mycoestrogens and cord steroids were measured. We fitted longitudinal models examining log-transformed mycoestrogen concentrations in relation to log-transformed hormones, adjusting for covariates. Secondarily, multivariable linear models examined associations at each time point (1st, 2nd, 3rd trimesters, delivery). We additionally considered effect modification by fetal sex. ZEN and its metabolite, α-zearalenol (α-ZOL), were detected in >93% and >75% of urine samples; >80% of placentas had detectable mycoestrogens. Longitudinal models from the full cohort exhibited few significant associations. In sex-stratified analyses, in pregnancies with male fetuses, estrone (E1) and free testosterone (fT) were inversely associated with ZEN (E1 %Δ: -6.68 95%CI: -12.34, -0.65; fT %Δ: -3.22 95%CI: -5.68, -0.70); while α-ZOL was positively associated with E2 (%Δ: 5.61 95%CI: -1.54, 9.85) in pregnancies with female fetuses. In analysis with cord hormones, urinary mycoestrogens were inversely associated with androstenedione (%Δ: 9.15 95%CI: 14.64, -3.30) in both sexes, and placental mycoestrogens were positively associated with cord fT (%Δ: 37.13, 95%CI: 4.86, 79.34) amongst male offspring. Findings support the hypothesis that mycoestrogens act as endocrine disruptors in humans, as in animal models and livestock. Additional work is needed to understand impacts on maternal and child health.


Assuntos
Sangue Fetal , Zearalenona , Humanos , Feminino , Sangue Fetal/química , Gravidez , Zearalenona/urina , Zearalenona/sangue , Adulto , Masculino , Hormônios Esteroides Gonadais/sangue , Exposição Materna , Estudos de Coortes , Zeranol/análogos & derivados , Zeranol/urina , Estradiol/sangue , Adulto Jovem , Placenta/química
12.
Diabetes ; 73(9): 1462-1472, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38869447

RESUMO

Macrophage (Mφ) plasticity is critical for normal wound repair; however, in type 2 diabetic wounds, Mφs persist in a low-grade inflammatory state that prevents the resolution of wound inflammation. Increased NLRP3 inflammasome activity has been shown in diabetic wound Mφs; however, the molecular mechanisms regulating NLRP3 expression and activity are unclear. Here, we identified that diabetic wound keratinocytes induce Nlrp3 gene expression in wound Mφs through IL-1 receptor-mediated signaling, resulting in enhanced inflammasome activation in the presence of pathogen-associated molecular patterns and damage-associated molecular patterns. We found that IL-1α is increased in human and murine wound diabetic keratinocytes compared with nondiabetic controls and directly induces Mφ Nlrp3 expression through IL-1 receptor signaling. Mechanistically, we report that the histone demethylase, JMJD3, is increased in wound Mφs late post-injury and is induced by IL-1α from diabetic wound keratinocytes, resulting in Nlrp3 transcriptional activation through an H3K27me3-mediated mechanism. Using genetically engineered mice deficient in JMJD3 in myeloid cells (Jmjd3f/flyz2Cre+), we demonstrate that JMJD3 controls Mφ-mediated Nlrp3 expression during diabetic wound healing. Thus, our data suggest a role for keratinocyte-mediated IL-1α/IL-1R signaling in driving enhanced NLRP3 inflammasome activity in wound Mφs. These data also highlight the importance of cell cross-talk in wound tissues and identify JMJD3 and the IL-1R signaling cascade as important upstream therapeutic targets for Mφ NLRP3 inflammasome hyperactivity in nonhealing diabetic wounds.


Assuntos
Inflamassomos , Histona Desmetilases com o Domínio Jumonji , Queratinócitos , Macrófagos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Receptores de Interleucina-1 , Transdução de Sinais , Cicatrização , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Queratinócitos/metabolismo , Animais , Histona Desmetilases com o Domínio Jumonji/metabolismo , Histona Desmetilases com o Domínio Jumonji/genética , Macrófagos/metabolismo , Camundongos , Transdução de Sinais/fisiologia , Humanos , Cicatrização/fisiologia , Receptores de Interleucina-1/metabolismo , Receptores de Interleucina-1/genética , Inflamassomos/metabolismo , Interleucina-1alfa/metabolismo , Interleucina-1alfa/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/genética , Masculino , Camundongos Endogâmicos C57BL
13.
JCI Insight ; 9(12)2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38912581

RESUMO

Plasmacytoid dendritic cells (pDCs) are first responders to tissue injury, where they prime naive T cells. The role of pDCs in physiologic wound repair has been examined, but little is known about pDCs in diabetic wound tissue and their interactions with naive CD4+ T cells. Diabetic wounds are characterized by increased levels of inflammatory IL-17A cytokine, partly due to increased Th17 CD4+ cells. This increased IL-17A cytokine, in excess, impairs tissue repair. Here, using human tissue and murine wound healing models, we found that diabetic wound pDCs produced excess IL-6 and TGF-ß and that these cytokines skewed naive CD4+ T cells toward a Th17 inflammatory phenotype following cutaneous injury. Further, we identified that increased IL-6 cytokine production by diabetic wound pDCs is regulated by a histone demethylase, Jumonji AT-rich interactive domain 1C histone demethylase (JARID1C). Decreased JARID1C increased IL-6 transcription in diabetic pDCs, and this process was regulated upstream by an IFN-I/TYK2/JAK1,3 signaling pathway. When inhibited in nondiabetic wound pDCs, JARID1C skewed naive CD4+ T cells toward a Th17 phenotype and increased IL-17A production. Together, this suggests that diabetic wound pDCs are epigenetically altered to increase IL-6 expression that then affects T cell phenotype. These findings identify a therapeutically manipulable pathway in diabetic wounds.


Assuntos
Células Dendríticas , Interleucina-6 , Células Th17 , Cicatrização , Animais , Feminino , Humanos , Masculino , Camundongos , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Histona Desmetilases com o Domínio Jumonji/metabolismo , Histona Desmetilases com o Domínio Jumonji/genética , Camundongos Endogâmicos C57BL , Células Th17/imunologia , Células Th17/metabolismo , Cicatrização/imunologia
14.
Epidemiology ; 35(5): 676-688, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38871635

RESUMO

BACKGROUND: Executive function, which develops rapidly in childhood, enables problem-solving, focused attention, and planning. Animal models describe executive function decrements associated with ambient air pollution exposure, but epidemiologic studies are limited. METHODS: We examined associations between early childhood air pollution exposure and school-aged executive function in 1235 children from three US pregnancy cohorts in the ECHO-PATHWAYS Consortium. We derived point-based residential exposures to ambient particulate matter ≤2.5 µm in aerodynamic diameter (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ) at ages 0-4 years from spatiotemporal models with a 2-week resolution. We assessed executive function across three domains, cognitive flexibility, working memory, and inhibitory control, using performance-based measures and calculated a composite score quantifying overall performance. We fitted linear regressions to assess air pollution and child executive function associations, adjusting for sociodemographic characteristics, maternal mental health, and health behaviors, and examined modification by child sex, maternal education, and neighborhood educational opportunity. RESULTS: In the overall sample, we found hypothesized inverse associations in crude but not adjusted models. Modified associations between NO 2 exposure and working memory by neighborhood education opportunity were present ( Pinteraction = 0.05), with inverse associations more pronounced in the "high" and "very high" categories. Associations of interest did not differ by child sex or maternal education. CONCLUSION: This work contributes to the evolving science regarding early-life environmental exposures and child development. There remains a need for continued exploration in future research endeavors, to elucidate the complex interplay between natural environment and social determinants influencing child neurodevelopment.


Assuntos
Poluição do Ar , Exposição Ambiental , Função Executiva , Dióxido de Nitrogênio , Material Particulado , Humanos , Feminino , Masculino , Pré-Escolar , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Material Particulado/análise , Dióxido de Nitrogênio/análise , Lactente , Estados Unidos , Exposição Ambiental/efeitos adversos , Criança , Estudos de Coortes , Memória de Curto Prazo/efeitos dos fármacos , Ozônio/análise , Ozônio/efeitos adversos , Recém-Nascido , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/efeitos adversos , Gravidez , Modelos Lineares
15.
Environ Pollut ; 357: 124463, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38942277

RESUMO

Increased systemic oxidative stress, implicated in adverse pregnancy outcomes for both mothers and fetuses, has been associated with gestational exposure to air pollutants such as polycyclic aromatic hydrocarbons (PAHs), fine particulate matter (PM2.5), and nitrogen dioxide (NO2). However, it is unclear whether exposure to pollutants at levels below the current air quality standards can increase oxidative stress in pregnant women. In a cohort of 305 pregnant persons residing in western New York, we examined the association between exposure to PM2.5, NO2, and PAHs (measured as urinary 1-hydroxypyrene) and urinary biomarkers of oxidative stress (malondialdehyde [MDA] and 8-hydroxy-2'-deoxyguanosine [8-OHdG]) measured in each trimester. After controlling for gestational stage, maternal age, lifestyles, and socioeconomic factors, each interquartile range (IQR) increase in 1-hydroxypyrene concentration (65.8 pg/ml) was associated with a 7.73% (95%CI: 3.18%,12.3%) higher in MDA levels throughout the pregnancy and in the first and second trimester. An IQR increase in PM2.5 concentration (3.20 µg/m3) was associated with increased MDA levels in the first trimester (8.19%, 95%CI: 0.28%,16.1%), but not the 2nd (-7.99%, 95% CI: 13.8%, -2.23%) or 3rd trimester (-2.81%, 95% CI: 10.0%, 4.38%). The average cumulative PM2.5 exposures in the 3-7 days before urine collection were associated with increased 8-OHdG levels during the second trimester, with the largest difference (22.6%; 95% CI: 3.46%, 41.7%) observed in relation to a one IQR increase in PM2.5 concentration in the previous 7 days. In contrast, neither oxidative stress biomarker was associated with NO2 exposure. Observed in pregnant women exposed to low-level air pollution, these findings expanded previously reported associations between systemic oxidative stress and high-level PM2.5 and PAH concentrations. Further, the first and second trimesters may be a susceptible window during pregnancy for oxidative stress responses to air pollution exposure.


Assuntos
8-Hidroxi-2'-Desoxiguanosina , Poluentes Atmosféricos , Biomarcadores , Estresse Oxidativo , Material Particulado , Hidrocarbonetos Policíclicos Aromáticos , Feminino , Gravidez , Humanos , Poluentes Atmosféricos/análise , Adulto , Material Particulado/análise , Biomarcadores/urina , Exposição Materna/estatística & dados numéricos , Dióxido de Nitrogênio , Adulto Jovem , New York , Pirenos , Poluição do Ar/estatística & dados numéricos , Malondialdeído/metabolismo , Estudos de Coortes
16.
JAMA Health Forum ; 5(5): e240901, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38758566

RESUMO

Importance: Since the full-scale Russian invasion, hospitals in Ukraine have been compelled to close or operate at reduced capacity due to inadequate supplies, damage, or destruction caused by war. Objective: To analyze hospital services in Ukraine during the period before and after the Russian invasion. Design, Setting, and Participants: Of the 450 hospitals currently functioning in Ukraine, a cross-sectional survey was carried out with the participation of 74 hospitals from 12 oblasts. Hospital administrators responded to an online survey with questions on the use of hospital services. Data were abstracted from hospital databases for the prewar period (before February 23, 2022) and during the war (February 23, 2022, to May 30, 2023). Main Outcomes and Measures: Hospital services (including emergency services, preventive services, screenings, laboratory tests, obstetrics, telehealth, pharmacy, and rehabilitation services) were compared during the prewar and war periods. Results: Of 450 Ukrainian hospitals in operation, 74 hospitals (16.0%) across 12 oblasts provided data for the current analyses. During the war, daily emergency admissions increased to 2830, compared with 2773 before the war. At the same time, hospitals reported reduced laboratory testing (72 [97%] vs 63 [85%]), tobacco education (52 [70%] vs 36 [49%]), cancer screening (49 [66%] vs 37 [50%]), gynecological services (43 [58%] vs 32 [43%]), rehabilitation services (37 [50%] vs 27 [36%]), pharmacy services (36 [49%] vs 27 [36%]), and telehealth programs (33 [45%] vs 21 [28%]). Hospitals reported additional difficulties during the war, including disruptions in the supply chain for essential equipment and pharmaceuticals, shortages of laboratory test kits, delays in the delivery of crucial medications, and problems around appropriate medication storage due to power outages. Conclusions and Relevance: The ongoing war has inflicted profound devastation on Ukraine's hospitals. The findings of this cross-sectional survey offer valuable insights into the formidable challenges that hospitals confront in war-affected regions and underscore the pressing necessity for bolstering support to sustain and enhance hospital services during wartime.


Assuntos
Hospitais , Ucrânia , Humanos , Estudos Transversais , Federação Russa , Hospitais/estatística & dados numéricos , Conflitos Armados
17.
J Affect Disord ; 360: 62-70, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38806063

RESUMO

BACKGROUND: The impacts of prenatal maternal affective symptoms on the placental structure are not well-established. Employing Geographic Information System (GIS) spatial autocorrelation, Moran's I, can help characterize placental thickness uniformity/variability and evaluate the impacts of maternal distress on placental topography. METHODS: This study (N = 126) utilized cohort data on prenatal maternal affective symptoms and placental 2D and 3D morphology. Prenatal maternal depression, stress, anxiety and sleep quality were scored for each trimester using the Edinburgh Postnatal Depression Scale (EPDS), Stressful Life Event Scale (SLE), Penn State Worry Questionnaire (PSWQ), and Pittsburgh Sleep Quality Index (PSQI), respectively. Placental shape was divided into Voronoi cells and thickness variability among these cells was computed using Moran's I for 4-nearest neighbors and neighbors within a 10 cm radius. Sex-stratified Spearman correlations and linear regression were used to study associations between mean placental thickness, placental GIS variables, placental weight and the average score of each maternal variable. RESULTS: For mothers carrying boys, poor sleep was associated with higher mean thickness (r = 0.308,p = 0.035) and lower placental thickness uniformity (r = -0.36,p = 0.012). Lower placental weight (r = 0.395,p = 0.003), higher maternal depression (r = -0.318,p = 0.019) and worry/anxiety (r = -0.362,p = 0.007) were associated with lower placental thickness uniformity for mothers carrying girls. LIMITATIONS: The study is exploratory and not all GIS models were developed. Excluding high-risk pregnancies prevented investigating pregnancy complications related hypotheses. A larger sample size is needed for greater confidence for clinical application. CONCLUSIONS: Placental topography can be studied using GIS theory and has shown that prenatal maternal affective symptoms and sleep have sex-specific associations with placental thickness.


Assuntos
Placenta , Complicações na Gravidez , Qualidade do Sono , Humanos , Feminino , Gravidez , Placenta/patologia , Adulto , Masculino , Complicações na Gravidez/psicologia , Depressão , Ansiedade , Fatores Sexuais , Sintomas Afetivos/fisiopatologia , Sistemas de Informação Geográfica , Mães/psicologia , Estresse Psicológico , Estudos de Coortes
18.
Environ Int ; 187: 108678, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38696977

RESUMO

BACKGROUND: Phthalate exposure may contribute to hypertensive disorders of pregnancy (HDP), including preeclampsia/eclampsia (PE/E), but epidemiologic studies are lacking. OBJECTIVES: To evaluate associations of pregnancy phthalate exposure with development of PE/E and HDP. METHODS: Using data from 3,430 participants in eight Environmental influences on Child Health Outcomes (ECHO) Program cohorts (enrolled from 1999 to 2019), we quantified concentrations of 13 phthalate metabolites (8 measured in all cohorts, 13 in a subset of four cohorts) in urine samples collected at least once during pregnancy. We operationalized outcomes as PE/E and composite HDP (PE/E and/or gestational hypertension). After correcting phthalate metabolite concentrations for urinary dilution, we evaluated covariate-adjusted associations of individual phthalates with odds of PE/E or composite HDP via generalized estimating equations, and the phthalate mixture via quantile-based g-computation. We also explored effect measure modification by fetal sex using stratified models. Effect estimates are reported as odds ratios (OR) with 95% confidence intervals (95% CIs). RESULTS: In adjusted analyses, a doubling of mono-benzyl phthalate (MBzP) and of mono (3-carboxypropyl) phthalate (MCPP) concentrations was associated with higher odds of PE/E as well as composite HDP, with somewhat larger associations for PE/E. For example, a doubling of MCPP was associated with 1.12 times the odds of PE/E (95%CI 1.00, 1.24) and 1.02 times the odds of composite HDP (95%CI 1.00, 1.05). A quartile increase in the phthalate mixture was associated with 1.27 times the odds of PE/E (95%CI 0.94, 1.70). A doubling of mono-carboxy isononyl phthalate (MCiNP) and of mono-carboxy isooctyl phthalate (MCiOP) concentrations were associated with 1.08 (95%CI 1.00, 1.17) and 1.11 (95%CI 1.03, 1.19) times the odds of PE/E. Effect estimates for PE/E were generally larger among pregnancies carrying female fetuses. DISCUSSION: In this study, multiple phthalates were associated with higher odds of PE/E and HDP. Estimates were precise and some were low in magnitude. Interventions to reduce phthalate exposures during pregnancy may help mitigate risk of these conditions.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Pré-Eclâmpsia , Humanos , Ácidos Ftálicos/urina , Gravidez , Feminino , Adulto , Pré-Eclâmpsia/urina , Pré-Eclâmpsia/epidemiologia , Poluentes Ambientais/urina , Hipertensão Induzida pela Gravidez/epidemiologia , Hipertensão Induzida pela Gravidez/urina , Exposição Materna/estatística & dados numéricos , Masculino , Saúde da Criança , Estudos de Coortes , Exposição Ambiental/análise , Adulto Jovem , Criança
19.
J Hypertens ; 42(8): 1399-1408, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38690915

RESUMO

OBJECTIVE: Although some studies have observed an association between birthweight and cardiovascular disease in adulthood, fewer have investigated whether birthweight is linked to cardiovascular health in early childhood. This study assesses the association between birthweight and cardiovascular outcomes in children 6 years of age. STUDY DESIGN: Birthweight, blood pressure (BP), and markers of arterial stiffness in children, including brachial artery distensibility and carotid-femoral pulse wave velocity (cfPWV), were obtained from 324 participants in The Infant Development and the Environment Study, a prospective multisite pregnancy cohort. Birthweight was converted into sex-specific birthweight-for-gestational-age (bw/ga) z -scores based on the INTERGROWTH-21st standard. Following 2017 American Academy of Pediatrics guidelines, SBP and DBP were transformed into sex, age, and height-specific z -scores. Associations between birthweight and cardiovascular outcomes were assessed using nested multivariable linear regression models among the overall and sex-stratified samples. RESULTS: Among the overall sample, bw/ga z -score was positively associated with cfPWV [b = 0.11 m/s, 95% confidence interval (CI): 0.01 m/s, 0.21 m/s] in crude and adjusted models. No associations between birthweight and cardiovascular outcomes were detected among the sex-stratified analyses. CONCLUSION: Overall, birthweight was not related to cardiovascular outcomes in children 6 years old. However, infants born with a higher birthweight may be at risk for higher cfPWV in childhood. Early intervention in pregnant people at risk of delivering high birthweight infants may be warranted if results are replicated.


Assuntos
Peso ao Nascer , Pressão Sanguínea , Rigidez Vascular , Humanos , Rigidez Vascular/fisiologia , Feminino , Criança , Masculino , Pressão Sanguínea/fisiologia , Estudos Longitudinais , Estudos Prospectivos , Análise de Onda de Pulso , Doenças Cardiovasculares/fisiopatologia , Artéria Braquial/fisiologia , Artéria Braquial/fisiopatologia , Recém-Nascido , Gravidez , Estudos de Coortes , Velocidade da Onda de Pulso Carótido-Femoral
20.
Front Reprod Health ; 6: 1298615, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38559324

RESUMO

Introduction: Exposure to endocrine disrupting chemicals (EDCs), such as phthalates, can negatively impact maternal and child health, contributing to impaired fetal growth, preterm birth, and pregnancy complications, as well as increased downstream risks of cardiometabolic disease and breast cancer. Notably, women of color (WOC) are the largest consumers of personal care products, which are a common source of EDC exposure. Methods: The Let's Reclaim Our Ancestral Roots (Let's R.O.A.R) Pilot Study developed an educational intervention delivered during pregnancy to promote reduced use of phthalate-containing hair care products (HCPs). This mixed-methods study included: (1) a quantitative analysis and (2) a qualitative analysis of the educational sessions and the semi-structured focus groups to evaluate the factors that influenced the hair care practices and product choices of WOC at various stages of life, including their current pregnancy (hereafter referred to as the hair journey). During the sessions, participants learned about EDCs (with a focus on phthalates), the unequal burden of exposure for WOC, adverse implications of exposure, and exposure reduction strategies. Focus group sessions provided insight into participants' hair journeys from childhood to the current pregnancy and explored factors during their hair product selection process. All sessions were transcribed and imported into NVivo Version 12 for coding and thematic analysis. Results: A total of 46 individuals were enrolled in the study, and 31 participated in an educational session. This current work synthesizes the qualitative analysis of this study. We identified two important life stages (before and after gaining agency over hair care practices and product choices) and three dominant themes related to HCP use: (1) products that impacted the hair journey, which involved all mentions of hair products, (2) factors that influenced the hair journey, which included individuals or entities that shaped participants' hair experiences, and (3) the relationship between hair and sense of self, where sense of self was defined as the alignment of one's inner and outer beauty. Conclusion: The themes intersected and impacted the participants' hair journey. Cultural integration was a sub-theme that overlapped within the dominant themes and participants discussed the effect of traditions on their hair experiences.

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