Building Capacity to study mixed metal-induced neurotoxicity in rural Bangladeshi children-A1

孟加拉国农村儿童研究混合金属引起的神经毒性的能力建设-A1

• 批准号: 10656538
• 负责人: Khalid M. Khan
• 金额: $ 53.77万
• 依托单位: SAM HOUSTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-14 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10656538
• 关键词: 2 year old; Accounting; Address; Adolescence; Adolescent; Affect; Age; Antibodies; Applied Skills; Area; Arsenic; Bangladesh; Bangladeshi; Behavior assessment; Behavioral Research; Biological Markers; Biometry; Blood; Blood specimen; Brain; Cadmium; Child; Child Development; Childhood; Collaborations; Country; Data; Data Analyses; Development; Economic Development; Economics; Education; Educational workshop; Environmental Pollutants; Environmental Risk Factor; Epidemiologist; Epidemiology; Etiology; Evaluation; Exposure to; Faculty; First Pregnancy Trimester; Goals; Health; Impairment; Individual; Infant; Iodide Peroxidase; Iodine; Iowa; Knowledge; Laboratories; Lead; Life; Link; Longitudinal cohort study; Manganese; Manuscripts; Measures; Mediating; Medical; Medicine; Metal exposure; Metals; Modeling; Mothers; Neurocognitive; Neurocognitive Deficit; Neuroepidemiology; Outcome; Performance; Persons; Phase; Population; Preparation; Property; Public Health; Research; Research Infrastructure; Research Institute; Research Methodology; Research Personnel; Risk; Rural; Scientist; Serum; Social Development; Standardization; System; Testing; Thyroglobulin antibody; Thyroid Diseases; Thyroid Hormones; Thyrotropin; Thyroxine; Toddler; Toxic effect; Training; Triiodothyronine; Universities; Writing; adolescent health; brain health; brain research; career; college; diarrheal disease; disability-adjusted life years; early pregnancy; epidemiologic data; epidemiology study; high risk; improved; international center; low and middle-income countries; maternal serum; nervous system disorder; neurobehavioral; neurodevelopment; neuroimaging; neurotoxicity; novel; prenatal; programs; recruit; research study; rural area; skills; symposium; systems research; thyroid disruption; tool; toxic metal; urinary; virtual; webinar

PROJECT SUMMARY The economic and public health burden of neurological diseases are remarkably high in Bangladesh with 5,344 cases per 100,000 people. Yet, the etiology of neurological disorders with respect to environmental pollutants, particularly toxic metals such as arsenic (As), lead (Pb), manganese (Mn), and cadmium (Cd), is poorly understood. These metals co-exist at moderate to high levels posing additional risk to children. Recent Bangladesh studies, including our own, have shown neurobehavioral (NB) effects associated with single metal exposure in children living in the rural areas. These detrimental effects, often subtle, potentially have long-term impact on the educational, social, and economic development of the population. This is, in part, due to the limited research capacity of local Bangladeshi researchers to properly evaluate the impact of mixed metal-induced impairment on brain function. To address this fundamental gap in critical research capacity, we plan to improve the research skills of Bangladeshi scientists by providing them the necessary training to appropriately investigate children’s brain vulnerability induced by metal co-exposure. The proposed study has assembled a group of U.S. investigators from Sam Houston State University, Columbia University, the University of Houston, Baylor College of Medicine, and the University of Iowa. The U.S. scientists will collaborate with the Bangladeshi researchers and faculty from the International Center for Diarrheal Disease Research, Bangladesh (icddr,b), Bangabandhu Sheikh Mujib Medical University (BSMMU), the largest medical university in Bangladesh, and North South University (NSU). Our goal is to improve the research capacity of scientists and clinicians by (i) organizing in-country and virtual yearly workshops/training and symposia on neuro-epidemiological research methodology and manuscript preparation; (ii) providing within the U.S. (and virtually), training on various neurobehavioral (NB) evaluation tools and data analysis; and (iii) involving the local researchers in two proposed epidemiological studies to be conducted in Bangladesh. In the first study, 600 adolescents from the Health Effects of Arsenic Longitudinal Study (HEALS) cohort in Araihazar will be evaluated for NB performance. Concurrently, adolescent blood samples will be analyzed for metals and thyroid hormone (TH) since metals are known to disrupt TH prenatally leading to poor NB performance in childhood. Free thyroxine (fT4), total triiodothyronine (tT3), thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) will be analyzed. The Behavioral Assessment and Research System (BARS) battery will be used for NB assessment. The second study will recruit 200 mother-child pairs from the Health and Demographic Surveillance System (HDSS) area in Matlab to assess if maternal metal mixture exposure is associated with TH disruption in early pregnancy, and in turn, if prenatal disruption of TH interferes with NB performance in young children. Together, these two studies will test if metal- induced neurotoxicity in early life, in part, mediate the relationships between metal co-exposure and NB.

项目概要 孟加拉国神经系统疾病的经济和公共卫生负担非常高，有 5,344 例 每 10 万人中的病例数。然而，与环境污染物有关的神经系统疾病的病因学， 特别是有毒金属，如砷（As）、铅（Pb）、锰（Mn）和镉（Cd）， 明白了。这些金属以中等到高含量共存，对儿童构成额外风险。最近的 孟加拉国的研究（包括我们自己的研究）已表明与单一金属相关的神经行为 (NB) 效应 农村地区儿童的暴露。这些有害影响通常是微妙的，但可能会产生长期的影响 对人民教育、社会和经济发展的影响。这在一定程度上是由于有限的 孟加拉国当地研究人员正确评估混合金属引起的影响的研究能力 大脑功能受损。为了解决关键研究能力方面的根本差距，我们计划改进 通过为孟加拉国科学家提供必要的培训以进行适当的调查，提高他们的研究技能 金属共同暴露导致儿童大脑脆弱性。 这项拟议的研究聚集了来自萨姆休斯顿州立大学的一组美国研究人员， 哥伦比亚大学、休斯顿大学、贝勒医学院和爱荷华大学。美国 科学家将与国际腹泻中心的孟加拉国研究人员和教员合作 孟加拉国疾病研究中心 (icddr,b)，最大的 Bangabandhu Sheikh Mujib 医科大学 (BSMMU) 孟加拉国医科大学和南北大学（NSU）。我们的目标是改进研究 通过以下方式提高科学家和临床医生的能力：(i) 组织国内和虚拟的年度研讨会/培训 关于神经流行病学研究方法和手稿准备的研讨会； (ii) 在规定范围内提供 美国（虚拟），各种神经行为（NB）评估工具和数据分析培训； (iii) 涉及 当地研究人员提议在孟加拉国进行两项流行病学研究。 在第一项研究中，来自砷健康影响纵向研究 (HEALS) 队列的 600 名青少年 Araihazar 将评估 NB 性能。同时，将对青少年血液样本进行分析 金属和甲状腺激素 (TH)，因为已知金属会在产前破坏 TH，导致 NB 不良 童年时的表现。游离甲状腺素 (fT4)、总三碘甲状腺原氨酸 (tT3)、促甲状腺激素 (TSH)、 将分析甲状腺过氧化物酶抗体（TPOAb）和甲状腺球蛋白抗体（TgAb）。行为方面 评估和研究系统（BARS）电池将用于NB评估。第二项研究将招募 来自 Matlab 健康和人口监测系统 (HDSS) 区域的 200 对母子进行评估 母体金属混合物暴露是否与妊娠早期 TH 破坏有关，反过来，如果产前 TH 的破坏会干扰幼儿的 NB 表现。这两项研究将共同​​测试金属是否 生命早期诱发的神经毒性在一定程度上介导了金属共暴露与 NB 之间的关系。