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1.
Pediatr Res ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867029

RESUMO

BACKGROUND: Sleep problems are reported for up to 80% of autistic individuals. We examined whether parsimonious sets of items derived from the Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) and the Brief Infant Sleep Questionnaire (BISQ) are superior to the standard M-CHAT-R in predicting subsequent autism spectrum disorder (ASD) diagnoses. METHODS: Participants from 11 Environmental influences on Child Health Outcomes (ECHO) cohorts were included. We performed logistic LASSO regression models with 10-fold cross-validation to identify whether a combination of items derived from the M-CHAT-R and BISQ are superior to the standard M-CHAT-R in predicting ASD diagnoses. RESULTS: The final sample comprised 1552 children. The standard M-CHAT-R had a sensitivity of 44% (95% CI: 34, 55), specificity of 92% (95% CI: 91, 94), and AUROC of 0.726 (95% CI: 0.663, 0.790). A higher proportion of children with ASD had difficulty falling asleep or resisted bedtime during infancy/toddlerhood. However, LASSO models revealed parental reports of sleep problems did not improve the accuracy of the M-CHAT-R in predicting ASD diagnosis. CONCLUSION: While children with ASD had higher rates of sleep problems during infancy/toddlerhood, there was no improvement in ASD developmental screening through the incorporation of parent-report sleep metrics. IMPACT: Parental-reported sleep problems are common in autism spectrum disorder (ASD). We investigated whether the inclusion of parental-reports of infant/toddler sleep patterns enhanced the effectiveness of developmental screening for autism. We reported higher rates of difficulty falling asleep and resisting bedtime during infancy and toddlerhood among children later diagnosed with ASD; however, we did not find an improvement in ASD developmental screening through the incorporation of parent-report sleep metrics. In our sample, the standard M-CHAT-R had a sensitivity of 39% among children of mothers with government insurance compared with a sensitivity of 53% among children of mothers with employer-based insurance.

2.
Am J Epidemiol ; 192(8): 1249-1263, 2023 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-36963379

RESUMO

The Environmental Influences on Child Health Outcomes (ECHO)-Wide Cohort Study (EWC), a collaborative research design comprising 69 cohorts in 31 consortia, was funded by the National Institutes of Health (NIH) in 2016 to improve children's health in the United States. The EWC harmonizes extant data and collects new data using a standardized protocol, the ECHO-Wide Cohort Data Collection Protocol (EWCP). EWCP visits occur at least once per life stage, but the frequency and timing of the visits vary across cohorts. As of March 4, 2022, the EWC cohorts contributed data from 60,553 children and consented 29,622 children for new EWCP data and biospecimen collection. The median (interquartile range) age of EWCP-enrolled children was 7.5 years (3.7-11.1). Surveys, interviews, standardized examinations, laboratory analyses, and medical record abstraction are used to obtain information in 5 main outcome areas: pre-, peri-, and postnatal outcomes; neurodevelopment; obesity; airways; and positive health. Exposures include factors at the level of place (e.g., air pollution, neighborhood socioeconomic status), family (e.g., parental mental health), and individuals (e.g., diet, genomics).


Assuntos
Poluição do Ar , Exposição Ambiental , Criança , Humanos , Estados Unidos/epidemiologia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Estudos de Coortes , Saúde da Criança , Poluição do Ar/análise , Avaliação de Resultados em Cuidados de Saúde
3.
J Autoimmun ; : 103117, 2023 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-37813804

RESUMO

Metals contaminants of the environment from mine waste have been implicated as contributing agents in autoimmune disease. The current study compares metals and autoimmunity in two Tribal communities residing in the Black Hills and the Bighorn Mountains geographical regions that are scattered with extant hard rock mines. With documented drinking water contamination in both communities, in vivo levels of more than half of the measured serum and urine metals differed between the two communities and were substantially different from their national median values. Serum autoantibodies associated with systemic autoimmune disease were rare or at low-level, but antibodies to denatured (single-stranded) DNA and thyroid-specific autoantibodies were commonly elevated, especially in women. A three-tier statistical modeling process was carried out to examine individual metals exposure as predictors of autoantibody levels. For the most part only weak positive associations between individual metals and systemic autoantibodies were found, although univariate quantile regression analysis showed positive statistical associations of serum lead and antimony with anti-chromatin and anti-histone autoantibodies. Using age and gender-adjusted multivariable statistical models, metals did not predict anti-thyroglobulin or -thyroid peroxidase significantly and metals were generally negative predictors of the other autoantibodies. Overall these results suggest that elevated levels of environmental metals and metalloids in these communities may result in suppression of autoantibodies associated with systemic autoimmune disease.

4.
Environ Monit Assess ; 195(7): 834, 2023 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-37303005

RESUMO

Meteorological (MET) data is a crucial input for environmental exposure models. While modeling exposure potential using geospatial technology is a common practice, existing studies infrequently evaluate the impact of input MET data on the level of uncertainty on output results. The objective of this study is to determine the effect of various MET data sources on the potential exposure susceptibility predictions. Three sources of wind data are compared: The North American Regional Reanalysis (NARR) database, meteorological aerodrome reports (METARs) from regional airports, and data from local MET weather stations. These data sources are used as inputs into a machine learning (ML) driven GIS Multi-Criteria Decision Analysis (GIS-MCDA) geospatial model to predict potential exposure to abandoned uranium mine sites in the Navajo Nation. Results indicate significant variations in results derived from different wind data sources. After validating the results from each source using the National Uranium Resource Evaluation (NURE) database in a geographically weighted regression (GWR), METARs data combined with the local MET weather station data showed the highest accuracy, with an average R2 of 0.74. We conclude that local direct measurement-based data (METARs and MET data) produce a more accurate prediction than the other sources evaluated in the study. This study has the potential to inform future data collection methods, leading to more accurate predictions and better-informed policy decisions surrounding environmental exposure susceptibility and risk assessment.


Assuntos
Fonte de Informação , Urânio , Monitoramento Ambiental , Aeroportos , Exposição Ambiental
5.
Toxicol Appl Pharmacol ; 456: 116292, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36270330

RESUMO

The Navajo Nation was heavily mined for uranium (U) during the cold-war leading to a legacy of >1100 abandoned U mining, milling and associated waste sites. The Navajo Birth Cohort Study was initiated to assess the effect of non-occupational legacy exposure to U during pregnancy on birth outcomes and child development. We report that 92% of babies with detectable urine U at birth were born from mothers who had urine U concentrations greater than national norms during pregnancy, indicative of prenatal exposure to U. To assess immune alterations associated with U exposure on both mothers and babies, we investigated associations between cytokine profiles and maternal U and associations of these measures with cytokine profiles in babies. Effect sizes for the differences in cytokine profiles were more evident among babies than mothers. Overall, there were seven cytokines (IFN-γ, IL-1ß, IL-2, IL-4, IL-10, GM-CSF, and TNF-α), for which the effect size for babies with higher than the national U concentrations was medium to large (ORs of 2.21 (1.08-4.52) through 1.71(0.76-3.83). In contrast, only three cytokines (IL-8, IL-12p70, and TNF-α) had effect sizes which almost reached medium strength (ORs of 1.64 (0.74-4.05) through 1.36 (0.65-2.87) in mothers with U above national norms. The effects of prenatal exposures to uranium and associated alterations in systemic immune responses resulting from U exposure could impact both maternal health as well as healthy child development through induction of inflammation, autoimmunity or other chronic diseases related to immune dysfunction that may affect long-term health.


Assuntos
Urânio , Feminino , Humanos , Recém-Nascido , Gravidez , Estudos de Coortes , Citocinas , Mães , Fator de Necrose Tumoral alfa , Urânio/toxicidade
6.
Toxicol Appl Pharmacol ; 411: 115362, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33279514

RESUMO

Arsenic exposure is well established to impair the function of zinc finger proteins, including PARP-1. Previous studies from our lab show that early developing T cells in the thymus are very sensitive to arsenite (As+3)-induced genotoxicity mediated through PARP-1 inhibition. Additionally, it has been shown that uranium (in the form of uranyl acetate, UA) also suppresses PARP-1 activity in HEK cells. However, very little is known about whether the As+3 metabolite, monomethylarsonous acid (MMA+3), also inhibits PARP-1 activity and if this is modified by combined exposures with other metals, such as uranium. In the present study, we found that MMA+3 significantly suppressed PARP-1 function, whereas UA at high concentrations significantly increased PARP-1 activity. To evaluate whether the effects on PARP-1 activity were mediated through oxidative stress, we measured the induction of hemoxygenase-1 (Hmox-1) expression by qPCR. MMA+3, but not UA, significantly induced oxidative stress; however, the inhibition of PARP-1 produced by MMA+3 was not reversed by the addition of the antioxidant, Tempol. Further evaluation revealed minimal interactive effects of MMA+3 and UA on PARP-1 function. Collectively, our results show that contrary to As+3, the suppressive effects of MMA+3 on PARP-1 were not substantially driven by oxidative stress. in mouse thymus cells. Results for this study provide important insights into the effects of MMA+3 and uranium exposures on PARP-1 function, which is essential for future studies focused on understanding the effects of complex environmentally relevant metal mixtures.


Assuntos
Compostos Organometálicos/toxicidade , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Inibidores de Poli(ADP-Ribose) Polimerases/toxicidade , Timo/efeitos dos fármacos , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Poli(ADP-Ribose) Polimerase-1/metabolismo , Timo/enzimologia
7.
Am J Public Health ; 111(9): 1645-1653, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34436921

RESUMO

We provide guidance for conducting clinical trials with Indigenous children in the United States. We drew on extant literature and our experience to describe 3 best practices for the ethical and effective conduct of clinical trials with Indigenous children. Case examples of pediatric research conducted with American Indian, Alaska Native, and Native Hawaiian communities are provided to illustrate these practices. Ethical and effective clinical trials with Indigenous children require early and sustained community engagement, building capacity for Indigenous research, and supporting community oversight and ownership of research. Effective engagement requires equity, trust, shared interests, and mutual benefit among partners over time. Capacity building should prioritize developing Indigenous researchers. Supporting community oversight and ownership of research means that investigators should plan for data-sharing agreements, return or destruction of data, and multiple regulatory approvals. Indigenous children must be included in clinical trials to reduce health disparities and improve health outcomes in these pediatric populations. Establishment of the Environmental Influences on Child Health Outcomes Institutional Development Award States Pediatric Clinical Trials Network (ECHO ISPCTN) in 2016 creates a unique and timely opportunity to increase Indigenous children's participation in state-of-the-art clinical trials.


Assuntos
/estatística & dados numéricos , Fortalecimento Institucional/organização & administração , Proteção da Criança/estatística & dados numéricos , Ensaios Clínicos como Assunto/normas , Indígenas Norte-Americanos/estatística & dados numéricos , Criança , Humanos , Projetos de Pesquisa , Segurança , Estados Unidos
8.
Indoor Air ; 31(4): 1109-1124, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33620109

RESUMO

Household heating using wood stoves is common practice in many rural areas of the United States (US) and can lead to elevated concentrations of indoor fine particulate matter (PM2.5 ). We collected 6-day measures of indoor PM2.5 during the winter and evaluated household and stove-use characteristics in homes at three rural and diverse study sites. The median indoor PM2.5 concentration across all homes was 19 µg/m3 , with higher concentrations in Alaska (median = 30, minimum = 4, maximum = 200, n = 10) and Navajo Nation homes (median = 29, minimum = 3, maximum = 105, n = 23) compared with Montana homes (median = 16, minimum = 2, maximum = 139, n = 59). Households that had not cleaned the chimney within the past year had 65% higher geometric mean PM2.5 compared to those with chimney cleaned within 6 months (95% confidence interval [CI]: -1, 170). Based on a novel wood stove grading method, homes with low-quality and medium-quality stoves had substantially higher PM2.5 compared to homes with higher-quality stoves (186% higher [95% CI: 32, 519] and 161% higher; [95% CI:27, 434], respectively). Our findings highlight the need for, and complex nature of, regionally appropriate interventions to reduce indoor air pollution in rural wood-burning regions. Higher-quality stoves and behavioral practices such as regular chimney cleaning may help improve indoor air quality in such homes.


Assuntos
Poluição do Ar em Ambientes Fechados , Material Particulado , Poluição do Ar em Ambientes Fechados/análise , Culinária , Monitoramento Ambiental , Características da Família , Humanos , Material Particulado/análise , Estados Unidos , Madeira
9.
Environ Res ; 190: 109943, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32750552

RESUMO

Navajo Nation residents are at risk for exposure to uranium and other co-occurring metals found in abandoned mine waste. The Navajo Birth Cohort Study (NBCS) was initiated in 2010 to address community concerns regarding the impact of chronic environmental exposure to metals on pregnancy and birth outcomes. The objectives of this paper were to 1) evaluate maternal urine concentrations of key metals at enrollment and delivery from a pregnancy cohort; and 2) compare the NBCS to the US general population by comparing representative summary statistical values. Pregnant Navajo women (N = 783, age range 14-45 years) were recruited from hospital facilities on the Navajo Nation during prenatal visits and urine samples were collected by trained staff in pre-screened containers. The U.S. Centers for Disease Control and Prevention (CDC), National Center for Environmental Health's (NCEH) Division of Laboratory Sciences (DLS) analyzed urine samples for metals. Creatinine-corrected urine concentrations of cadmium decreased between enrollment (1st or 2nd trimester) and delivery (3rd trimester) while urine uranium concentrations were not observed to change. Median and 95th percentile values of maternal NBCS urine concentrations of uranium, manganese, cadmium, and lead exceeded respective percentiles for National Health and Nutrition Evaluation Survey (NHANES) percentiles for women (ages 14-45 either pregnant or not pregnant.) Median NBCS maternal urine uranium concentrations were 2.67 (enrollment) and 2.8 (delivery) times greater than the NHANES median concentration, indicating that pregnant Navajo women are exposed to metal mixtures and have higher uranium exposure compared to NHANES data for women. This demonstrates support for community concerns about uranium exposure and suggests a need for additional analyses to evaluate the impact of maternal metal mixtures exposure on birth outcomes.


Assuntos
Exposição Ambiental , Urânio , Adolescente , Adulto , Estudos de Coortes , Exposição Ambiental/análise , Feminino , Humanos , Pessoa de Meia-Idade , Inquéritos Nutricionais , Gravidez , Adulto Jovem
10.
Environ Res ; 188: 109709, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32526495

RESUMO

The Environmental influences on Child Health Outcomes (ECHO) Program is a research initiative funded by the National Institutes of Health that capitalizes on existing cohort studies to investigate the impact of early life environmental factors on child health and development from infancy through adolescence. In the initial stage of the program, extant data from 70 existing cohort studies are being uploaded to a database that will be publicly available to researchers. This new database will represent an unprecedented opportunity for researchers to combine data across existing cohorts to address associations between prenatal chemical exposures and child neurodevelopment. Data elements collected by ECHO cohorts were determined via a series of surveys administered by the ECHO Data Analysis Center. The most common chemical classes quantified in multiple cohorts include organophosphate pesticides, polychlorinated biphenyls, polybrominated diphenyl ethers, environmental phenols (including bisphenol A), phthalates, and metals. For each of these chemicals, at least four ECHO cohorts also collected behavioral data during infancy/early childhood using the Child Behavior Checklist. For these chemicals and this neurodevelopmental assessment (as an example), existing data from multiple ECHO cohorts could be pooled to address research questions requiring larger sample sizes than previously available. In addition to summarizing the data that will be available, the article also describes some of the challenges inherent in combining existing data across cohorts, as well as the gaps that could be filled by the additional data collection in the ECHO Program going forward.


Assuntos
Poluentes Ambientais , Bifenilos Policlorados , Adolescente , Criança , Saúde da Criança , Pré-Escolar , Estudos de Coortes , Exposição Ambiental , Poluentes Ambientais/toxicidade , Feminino , Éteres Difenil Halogenados , Humanos , Compostos Organofosforados , Gravidez
11.
Tob Control ; 29(5): 570-576, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31462578

RESUMO

INTRODUCTION: American Indians and Alaska Natives face disproportionately high rates of smoking and secondhand smoke (SHS) exposure. The Cheyenne River Sioux Tribe (CRST) is among the few Tribal Nations controlling commercial tobacco exposures in public and work places. We had an opportunity to explore effects of the new commercial tobacco-free policy (implemented in 2015) in an environmental health study (2014-2016) that collected information about commercial tobacco use and SHS prevalence and examined predictor variables of serum cotinine concentrations. METHODS: Self-reported survey data were used in quantile regression statistical modelling to explore changes in cotinine levels, based on smoking status, smokeless tobacco consumption and SHS exposure. RESULTS: From enrolled 225 adults, 51% (N=114) were current smokers. Among 88 non-tobacco users, 35 (40%) reported current SHS exposure. Significant differences in cotinine median concentrations were found among participants with and without current SHS exposure. Extremely high cotinine concentrations (~100 times larger than the median) were detected in some non-tobacco users. After implementing the new smoke-free air Tribal policy, cotinine decreased in participants with intermediate (3-15 ng/mL, non-tobacco users with SHS exposure) and high (>15 ng/mL, mainly tobacco users) cotinine levels showing association with an abatement of opportunities for SHS exposure. Significant predictors of cotinine levels were sampling year, current smoking and tobacco chewing. No gender differences were observed in cotinine. CONCLUSIONS: Our results show decrease in cotinine concentrations in CRST participants since implementation of their 'Smoke-Free Clean Air Act' in 2015.


Assuntos
Indígena Americano ou Nativo do Alasca , Cotinina/sangue , Política de Saúde , Prevenção do Hábito de Fumar , Fumar/sangue , Poluição por Fumaça de Tabaco/efeitos adversos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Matern Child Nutr ; 16(3): e12961, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32026554

RESUMO

Proper nutrition during pregnancy is vital to maternal health and fetal development and may be challenging for Navajo Nation residents because access to affordable and healthy foods is limited. It has been several decades since reported diet quality during pregnancy was examined on Navajo Nation. We present the first study to estimate iodine intake and use the Healthy Eating Index (HEI-2015) to assess maternal diet quality among pregnant women in the Navajo Birth Cohort Study (NBCS). Based on dietary intake data derived from food frequency questionnaires, overall estimated micronutrient intake has remained similar since the last assessment in 1981, with potential improvements evident for folate and niacin. A high proportion of women (>50%) had micronutrient intakes from dietary sources below the Estimated Average Requirements during pregnancy. The median urinary iodine concentration for NBCS women (90.8 µg/L; 95% CI [80, 103.5]) was less than adequate and lower than concentrations reported for pregnant women that participated in the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2014. Overall, average diet quality of NBCS women estimated using the HEI-2015 (62.4; 95% CI [60.7, 64.0]) was similar to that reported for women of child-bearing age and pregnant women in NHANES. Although, NBCS women had diets high in added sugar, with sugar-sweetened beverages as the primary contributors. Our study provides updated insights on maternal diet quality that can inform health and nutrition initiatives in Navajo communities emphasizing nutrition education and access to prenatal vitamins and calcium, iodine, and vitamin E dense foods.


Assuntos
Indígena Americano ou Nativo do Alasca/estatística & dados numéricos , Dieta/métodos , Dieta/normas , Fenômenos Fisiológicos da Nutrição Materna , Inquéritos Nutricionais/métodos , Estado Nutricional , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Inquéritos Nutricionais/estatística & dados numéricos , Gravidez , Gestantes , Adulto Jovem
13.
J Autoimmun ; 99: 15-23, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30878168

RESUMO

Specific autoantibodies were assessed among residents of the Navajo Nation in New Mexico chronically exposed to metal mixtures from uranium mine wastes and in drinking water supplies. Age and the extent of exposure to legacy waste from 100 abandoned uranium mine and mill sites were associated with antibodies to denatured DNA, previously known to be an early indicator of medication-induced autoimmunity. Surprisingly, autoantibodies to native DNA and/or chromatin were also linked to environmental exposure, specifically uranium consumption through drinking water for both men and women, while urinary arsenic was negatively associated with these autoantibodies in women. These findings suggest that contaminants derived from uranium mine waste enhanced development of autoantibodies in some individuals, while arsenic may be globally immunosuppressive with gender-specific effects. Specific autoantibodies may be a sensitive indicator of immune perturbation by environmental toxicants, an adverse effect not considered in current drinking water standards or regulatory risk assessment evaluations.


Assuntos
Autoimunidade , Exposição Ambiental/efeitos adversos , Mineração , Características de Residência , Urânio/efeitos adversos , Arsênio/efeitos adversos , Autoanticorpos , Suscetibilidade a Doenças , Feminino , Geografia , Humanos , Masculino , New Mexico/epidemiologia , Vigilância em Saúde Pública , Contaminação Radioativa da Água
14.
Environ Health ; 18(1): 46, 2019 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-31072361

RESUMO

BACKGROUND: There is increasing interest in examining the consequences of simultaneous exposures to chemical mixtures. However, a consensus or recommendations on how to appropriately select the statistical approach analyzing the health effects of mixture exposures which best aligns with study goals has not been well established. We recognize the limitations that existing methods have in effectively reducing data dimension and detecting interaction effects when analyzing chemical mixture exposures collected in high dimensional datasets with varying degrees of variable intercorrelations. In this research, we aim to examine the performance of a two-step statistical approach in addressing the analytical challenges of chemical mixture exposures using two simulated data sets, and an existing data set from the Navajo Birth Cohort Study as a representative case study. METHODS: We propose to use a two-step approach: a robust variable selection step using the random forest approach followed by adaptive lasso methods that incorporate both dimensionality reduction and quantification of the degree of association between the chemical exposures and the outcome of interest, including interaction terms. We compared the proposed method with other approaches including (1) single step adaptive lasso; and (2) two-step Classification and regression trees (CART) followed by adaptive lasso method. RESULTS: Utilizing simulated data sets and applying the method to a real-life dataset from the Navajo Birth Cohort Study, we have demonstrated good performance of the proposed two-step approach. Results from the simulation datasets indicated the effectiveness of variable dimension reduction and reliable identification of a parsimonious model compared to other methods: single-step adaptive lasso or two-step CART followed by adaptive lasso method. CONCLUSIONS: Our proposed two-step approach provides a robust way of analyzing the effects of high-throughput chemical mixture exposures on health outcomes by combining the strengths of variable selection and adaptive shrinkage strategies.


Assuntos
Exposição Ambiental/efeitos adversos , Saúde Ambiental/métodos , Poluentes Ambientais/efeitos adversos , Adolescente , Adulto , Estudos de Coortes , Simulação por Computador , Feminino , Humanos , Pessoa de Meia-Idade , Modelos Estatísticos , Gravidez , Sudoeste dos Estados Unidos , Adulto Jovem
15.
Child Care Health Dev ; 45(5): 709-718, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31276599

RESUMO

BACKGROUND: The Ages and Stages Questionnaires-Third Edition (ASQ-3) is a parent-completed screening to identify young children at-risk for developmental delays in the United States and internationally. Federal programs operating on Navajo Nation use the ASQ-3 to determine the need for early intervention services, even though the ASQ-3 national sample used to establish cutoff scores for referral included only 1% Native American children. OBJECTIVES: The current study aimed to compare the ASQ-3 results from a sample of Navajo infants to those from a representative national U.S. sample and to examine the specificity and sensitivity of the ASQ-3 in Navajo population. METHODS: The sample included 530 Navajo infants (47.3% males) aged between 1 and 13 months who lived in remote and rural areas across the Navajo Nation. Children's development was assessed during home visits at 2-, 6-, 9-, and 12-month assessment windows. RESULTS: Results showed that after 6 months, Navajo children had lower mean scores and higher percentages of children at-risk for developmental delays than those from the national sample. The sensitivities and specificities, estimated using a Bayesian diagnostic approach under both conservative and nonconservative prior range choices, suggested a comparable validity performance to that from other ASQ-3 studies. DISCUSSION: The results of this study along with our ongoing comprehensive assessments at 4 years of age inform current programs working with Navajo children to improve early identification of developmental delays.


Assuntos
Deficiências do Desenvolvimento/diagnóstico , Teorema de Bayes , Desenvolvimento Infantil , Comunicação , Assistência à Saúde Culturalmente Competente/métodos , Deficiências do Desenvolvimento/psicologia , Feminino , Humanos , Lactente , Masculino , Programas de Rastreamento/métodos , Pais , Resolução de Problemas , Psicometria , Desempenho Psicomotor , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fatores Socioeconômicos , Inquéritos e Questionários
16.
J Toxicol Environ Health A ; 81(13): 535-548, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29641933

RESUMO

More than 500 abandoned uranium (U) mines within the Navajo Nation contribute U, arsenic (As) and other metals to groundwater, soil and potentially air through airborne transport. The adverse cardiovascular health effects attributed to cumulative exposure to these metals remains uncertain. The aim of this study was to examine whether environmental exposure to these metals may promote or exacerbate the oxidation of low-density lipoprotein (LDL) cholesterol in this Native American population. The correlation of cardiovascular biomarkers (oxidized LDL (oxLDL) and C-reactive protein (CRP)) from a Navajo cohort (n = 252) with mean annual As and U intakes from water and urine metals was estimated using linear regression. Proof-of-concept assays were performed to investigate whether As and U directly oxidize human LDL. Mean annual As intake from water was positively and significantly associated with oxLDL, but not CRP in this study population, while U intake estimates were negatively associated with oxLDL. In an acellular system, As, but not U, directly oxidized the apolipoprotein B-100 component of purified human LDL. Neither metal promoted lipid peroxidation of the LDL particle. Both the population and lab results are consistent with the hypothesis that As promotes oxidation of LDL, a crucial step in vascular inflammation and chronic vascular disease. Conversely, for outcomes related to U, negative associations were observed between U intake and oxLDL, and U only minimally altered human LDL in direct exposure experiments. Only urine U was correlated with CRP, whereas no other metals in water or urine were apparently reliable predictors of this inflammatory marker.


Assuntos
Arsênio/urina , Proteína C-Reativa/metabolismo , Exposição Ambiental , Poluentes Ambientais/urina , Lipoproteínas LDL/sangue , Urânio/urina , Adulto , Idoso , Biomarcadores/urina , LDL-Colesterol/metabolismo , Estudos Transversais , Feminino , Humanos , Indígenas Norte-Americanos , Masculino , Pessoa de Meia-Idade , New Mexico , Oxirredução , Medição de Risco
17.
Toxicol Appl Pharmacol ; 291: 13-20, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26627003

RESUMO

Uranium has radiological and non-radiological effects within biological systems and there is increasing evidence for genotoxic and carcinogenic properties attributable to uranium through its heavy metal properties. In this study, we report that low concentrations of uranium (as uranyl acetate; <10 µM) is not cytotoxic to human embryonic kidney cells or normal human keratinocytes; however, uranium exacerbates DNA damage and cytotoxicity induced by hydrogen peroxide, suggesting that uranium may inhibit DNA repair processes. Concentrations of uranyl acetate in the low micromolar range inhibited the zinc finger DNA repair protein poly(ADP-ribose) polymerase (PARP)-1 and caused zinc loss from PARP-1 protein. Uranyl acetate exposure also led to zinc loss from the zinc finger DNA repair proteins Xeroderma Pigmentosum, Complementation Group A (XPA) and aprataxin (APTX). In keeping with the observed inhibition of zinc finger function of DNA repair proteins, exposure to uranyl acetate enhanced retention of induced DNA damage. Co-incubation of uranyl acetate with zinc largely overcame the impact of uranium on PARP-1 activity and DNA damage. These findings present evidence that low concentrations of uranium can inhibit DNA repair through disruption of zinc finger domains of specific target DNA repair proteins. This may provide a mechanistic basis to account for the published observations that uranium exposure is associated with DNA repair deficiency in exposed human populations.


Assuntos
Reparo do DNA/efeitos dos fármacos , Reparo do DNA/fisiologia , Inibidores de Poli(ADP-Ribose) Polimerases/toxicidade , Poli(ADP-Ribose) Polimerases/metabolismo , Urânio/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Células HEK293 , Humanos , Poli(ADP-Ribose) Polimerase-1
18.
Environ Sci Technol ; 50(21): 11539-11548, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27704799

RESUMO

We applied spectroscopy, microscopy, diffraction, and aqueous chemistry methods to investigate the persistence of metals in water and sediments from the Animas River 13 days after the Gold King Mine spill (August 5, 2015). The Upper Animas River watershed, located in San Juan Colorado, is heavily mineralized and impacted by acid mine drainage, with low pH water and elevated metal concentrations in sediments (108.4 ± 1.8 mg kg-1 Pb, 32.4 ± 0.5 mg kg-1 Cu, 729.6 ± 5.7 mg kg-1 Zn, and 51 314.6 ± 295.4 mg kg-1 Fe). Phosphate and nitrogen species were detected in water and sediment samples from Farmington, New Mexico, an intensive agricultural area downstream from the Animas River, while metal concentrations were low compared to those observed upstream. Solid-phase analyses of sediments suggest that Pb, Cu, and Zn are associated with metal-bearing jarosite and other minerals (e.g., clays, Fe-(oxy)hydroxides). The solubility of jarosite at near-neutral pH and biogeochemical processes occurring downstream could affect the stability of metal-bearing minerals in river sediments. This study contributes relevant information about the association of metal mixtures in a heavy mineralized semiarid region, providing a foundation to better understand long-term metal release in a public and agricultural water supply.


Assuntos
Ouro , Rios/química , Monitoramento Ambiental , Sedimentos Geológicos/química , Metais Pesados , Água , Poluentes Químicos da Água
19.
Environ Sci Technol ; 49(14): 8506-14, 2015 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-26158204

RESUMO

The chemical interactions of U and co-occurring metals in abandoned mine wastes in a Native American community in northeastern Arizona were investigated using spectroscopy, microscopy and aqueous chemistry. The concentrations of U (67-169 µg L(-1)) in spring water samples exceed the EPA maximum contaminant limit of 30 µg L(-1). Elevated U (6,614 mg kg(-1)), V (15,814 mg kg(-1)), and As (40 mg kg(-1)) concentrations were detected in mine waste solids. Spectroscopy (XPS and XANES) solid analyses identified U (VI), As (-I and III) and Fe (II, III). Linear correlations for the release of U vs V and As vs Fe were observed for batch experiments when reacting mine waste solids with 10 mM ascorbic acid (∼pH 3.8) after 264 h. The release of U, V, As, and Fe was at least 4-fold lower after reaction with 10 mM bicarbonate (∼pH 8.3). These results suggest that U-V mineral phases similar to carnotite [K2(UO2)2V2O8] and As-Fe-bearing phases control the availability of U and As in these abandoned mine wastes. Elevated concentrations of metals are of concern due to human exposure pathways and exposure of livestock currently ingesting water in the area. This study contributes to understanding the occurrence and mobility of metals in communities located close to abandoned mine waste sites.


Assuntos
Resíduos Industriais/análise , Metais/análise , Mineração , Urânio/análise , Arizona , Ácido Ascórbico/química , Monitoramento Ambiental/métodos , Humanos , Indígenas Norte-Americanos , Ferro/análise , Espectroscopia Fotoeletrônica , Resíduos Sólidos , Urânio/química , Vanádio/análise , Vanádio/química , Espectroscopia por Absorção de Raios X
20.
J Expo Sci Environ Epidemiol ; 34(1): 3-22, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37739995

RESUMO

BACKGROUND: Advances in drinking water infrastructure and treatment throughout the 20th and early 21st century dramatically improved water reliability and quality in the United States (US) and other parts of the world. However, numerous chemical contaminants from a range of anthropogenic and natural sources continue to pose chronic health concerns, even in countries with established drinking water regulations, such as the US. OBJECTIVE/METHODS: In this review, we summarize exposure risk profiles and health effects for seven legacy and emerging drinking water contaminants or contaminant groups: arsenic, disinfection by-products, fracking-related substances, lead, nitrate, per- and polyfluorinated alkyl substances (PFAS) and uranium. We begin with an overview of US public water systems, and US and global drinking water regulation. We end with a summary of cross-cutting challenges that burden US drinking water systems: aging and deteriorated water infrastructure, vulnerabilities for children in school and childcare facilities, climate change, disparities in access to safe and reliable drinking water, uneven enforcement of drinking water standards, inadequate health assessments, large numbers of chemicals within a class, a preponderance of small water systems, and issues facing US Indigenous communities. RESULTS: Research and data on US drinking water contamination show that exposure profiles, health risks, and water quality reliability issues vary widely across populations, geographically and by contaminant. Factors include water source, local and regional features, aging water infrastructure, industrial or commercial activities, and social determinants. Understanding the risk profiles of different drinking water contaminants is necessary for anticipating local and general problems, ascertaining the state of drinking water resources, and developing mitigation strategies. IMPACT STATEMENT: Drinking water contamination is widespread, even in the US. Exposure risk profiles vary by contaminant. Understanding the risk profiles of different drinking water contaminants is necessary for anticipating local and general public health problems, ascertaining the state of drinking water resources, and developing mitigation strategies.


Assuntos
Arsênio , Água Potável , Criança , Humanos , Qualidade da Água , Reprodutibilidade dos Testes , Envelhecimento
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