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: 10488220
• 负责人: Khalid M. Khan
• 金额: $ 53.75万
• 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/10488220
• 关键词: 2 year old; Accounting; Address; Adolescence; Adolescent; Affect; Age; Antibodies; 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; Educational workshop; Environmental Pollutants; Environmental Pollution; Environmental Risk Factor; Epidemiologist; Epidemiology; Etiology; Evaluation; Exposure to; Faculty; First Pregnancy Trimester; Goals; Health; Impairment; Individual; Infant; Institutes; 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 Gland; 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.

项目总结 在孟加拉国，神经系统疾病造成的经济和公共卫生负担非常高，有5344人 每10万人中就有病例。然而，与环境污染物有关的神经疾病的病因学， 特别是有毒金属，如砷(As)、铅(Pb)、锰(Mn)和镉(Cd)，情况很差 明白了。这些金属以中等到高水平共存，给儿童带来了额外的风险。近期 孟加拉国的研究，包括我们自己的研究，已经显示了与单一金属相关的神经行为(NB)效应 对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，可能具有长期的影响。 对人口的教育、社会和经济发展的影响。这在一定程度上是由于 孟加拉当地研究人员适当评估混合金属引起的影响的研究能力 对大脑功能的损害。为了解决关键研究能力的这一根本差距，我们计划改进 孟加拉国科学家的研究技能，为他们提供必要的培训，以便进行适当的研究 金属联合暴露引起的儿童脑部脆弱性。 这项拟议的研究召集了来自萨姆·休斯顿州立大学的一组美国调查人员， 哥伦比亚大学、休斯顿大学、贝勒医学院和爱荷华大学。美国 科学家将与孟加拉的研究人员和国际腹泻中心的教职员工合作 孟加拉国疾病研究中心(ICDDR，b)，最大的班加杜谢赫·穆吉布医科大学(BSMMU) 孟加拉医科大学和南北方大学。我们的目标是改进研究 通过下列方式提高科学家和临床医生的能力：(I)组织国内和虚拟年度讲习班/培训和 关于神经流行病学研究方法和手稿准备的研讨会；(2)在 美国(和虚拟)，关于各种神经行为(NB)评估工具和数据分析的培训；以及(Iii)涉及 当地研究人员建议在孟加拉国进行两项流行病学研究。 在第一项研究中，来自砷对健康影响的纵向研究(HEALS)队列中的600名青少年 将对Araihazar进行NB性能评估。同时，青少年的血液样本将被分析为 金属和甲状腺激素(TH)，因为已知金属会在产前扰乱TH，导致不良的Nb 童年时期的表演。游离甲状腺激素(FT4)、总三碘甲状腺原氨酸(TT3)、促甲状腺激素(TSH)、 分析甲状腺过氧化物酶抗体(TPOAb)和甲状腺球蛋白抗体(TgAb)。《行为学派》 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)地区的200对母婴评估 如果母亲接触金属混合物与妊娠早期的TH中断有关，反过来，如果产前 TH的中断干扰了幼儿的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，在一定程度上调节了金属联合暴露与NB之间的关系。