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

项目摘要 在孟加拉国，神经系统疾病的经济和公共卫生负担非常高， 每10万人中的病例数。然而，神经系统疾病的病因学与环境污染物， 特别是有毒金属如砷（As）、铅（Pb）、锰（Mn）和镉（Cd）， 明白这些金属以中等至高水平共存，对儿童构成额外风险。最近 孟加拉国的研究，包括我们自己的研究，已经表明与单一金属有关的神经行为（NB）影响 生活在农村地区的儿童的接触。这些有害影响，往往是微妙的，潜在的长期影响， 对人口的教育、社会和经济发展的影响。部分原因是， 孟加拉国当地研究人员的研究能力，以适当评估混合金属引起的影响， 大脑功能受损。为了解决关键研究能力的这一根本差距，我们计划提高 孟加拉国科学家的研究技能，为他们提供必要的培训， 重金属复合暴露诱发儿童脑损伤的研究 这项拟议中的研究召集了一组来自萨姆休斯顿州立大学的美国调查人员， 哥伦比亚大学、休斯顿大学、贝勒医学院和爱荷华州大学。美国 科学家们将与来自国际腹泻中心的孟加拉国研究人员和教师合作， 疾病研究，孟加拉国（icddr，B），Bangabandhu Sheikh Mujib医科大学（BSMMU），最大的 孟加拉医科大学和南北大学（NSU）。我们的目标是改进研究 科学家和临床医生的能力，方法是：㈠组织国内和虚拟年度讲习班/培训， 关于神经流行病学研究方法和手稿准备的专题讨论会;（ii）在 美国(and虚拟），各种神经行为（NB）评估工具和数据分析的培训;以及（iii）涉及 在孟加拉国进行的两项拟议的流行病学研究中，当地的研究人员。 在第一项研究中，600名来自砷对健康影响纵向研究（HEALS）队列的青少年， 将对Araihazar进行NB性能评价。同时，将分析青少年血液样本， 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 童年的表现。游离甲状腺素（fT 4）、总三碘甲状腺原氨酸（tT 3）、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 评估和研究系统（BARS）组合将用于NB评估。第二项研究将招募 来自健康和人口监测系统（HDSS）地区的200对母子在Matlab中进行评估， 如果母体金属混合物暴露与妊娠早期TH破坏相关，反过来，如果产前 TH的中断干扰幼儿的NB表现。这两项研究将共同测试金属- 在生命早期诱导的神经毒性，部分介导金属共暴露和NB之间的关系。

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.