Central auditory processing abnormalities as an indicator of pediatric heavy metal neurotoxicity

项目摘要 手工小规模采金社区面临重金属/类金属的极高风险 暴露包括汞（Hg）、铅（Pb）、砷（As）和锰（Mn）， 对发育中的中枢神经系统（CNS）的影响。儿童时期接触这些金属可能导致 终身教育和就业机会减少。早期识别重金属神经毒性具有重要意义 一直具有挑战性，但初步工作表明，中央听觉处理（CAP）可能与重 金属暴露与早期神经认知变化相关。通过我们以前的工作，我们有：1） 开发了一种无线、现场可部署的外围和中央听力评估系统，适用于 发展中国家，2）在尼加拉瓜建立了研究合作，3）表明，中央 听觉测试可用于评估大脑功能。本研究将确定便携式、移动的 中枢听觉测试可以识别出有明显重金属神经毒性的儿童。最低限度培训 技术人员将利用创新的移动的平板电脑平台进行听力测定和全面的 CAP测试[双耳两分数字（DD），反相噪声和信号测试（N 0 Spi），间隙检测阈值（GDT）， 拉丁美洲西班牙语听力噪声测试（LASHINT）和固定水平频率测试（FLFT）] 生活在哥伦比亚小规模手工开采金矿社区的大批儿童（200名）（6 - 18岁）。数据将被上传 移动的数据库平台（REDCap）沿着详细的社会经济和风险因素数据。此外，本发明还提供了一种方法， 收集趾甲和干血斑（DBS）样本，并分析5种重 使用电感耦合等离子体质谱法（ICP-MS）分析金属（Pb、Hg、As、Mn和Al）。的 这些金属的浓度将使用回归分析与CAP测试性能相关， 非参数ANOVA（Kruskal-Wallis）分析将用于评估儿童之间的差异， 金属水平高于参考范围内的水平。拟议的工作将建立在现有的 研究能力和与尼加拉瓜两个主要合作机构的合作，通过：1）发展 研究能力和提供非常适合偏远贫困环境的仪器，2） 调整和培训研究人员在数据库（REDCap）的设计和实施，3）提供一个 通过培训为今后的全面流行病学研究奠定基础，4）指导巴布亚新几内亚 研究人员在先进的研究设计和方法，5）提供额外的专业知识， 感兴趣的领域（如中枢听觉处理障碍，重金属神经毒性），6）促进 MMO和UNAN-Leon CISTA之间的研究合作伙伴关系。该项目将提供初步数据， 重金属暴露和中枢听觉测试表现，这将构成后续补助金的基础 我们的巴布亚新几内亚同事提交的意见书，以解决这一重要的环境卫生问题。

Project Abstract Artisanal small-scale gold mining (ASGM) communities are at extremely high risk for heavy metal / metalloid exposure including mercury (Hg), lead (Pb), arsenic (As), and manganese (Mn) with potential irreversible effects on the developing central nervous system (CNS). Exposure to these metals in childhood could lead to a lifelong reduction in educational and job opportunities. Early identification of heavy metal neurotoxicity has been challenging, but preliminary work suggests central auditory processing (CAP) may correlate with heavy metal exposure and correlate with early neurocognitive changes. Through our previous work we have: 1) developed a wireless, field deployable peripheral and central hearing assessment system suitable for the developing world, 2) established research collaborations in Nicaragua and 3) demonstrated that central auditory testing can be used to assess brain function. This study will determine whether portable, mobile central auditory testing can identify children with significant heavy metal neurotoxicity. Minimally trained technicians will utilize an innovative mobile tablet-based platform to perform audiometry and comprehensive CAP tests [Dichotic Digits (DD), antiphase noise and signal testing (N0Spi), Gap Detection Threshold (GDT), Latin American Spanish Hearing in Noise Testing (LASHINT), and Fixed Level Frequency Testing (FLFT)] on a large cohort (200) of children (6 – 18 years) living in a Nicaraguan ASGM communities. Data will be uploaded to a mobile database platform (REDCap) along with detailed socioeconomic and risk factor data. In addition, toenail and dried blood spot (DBS) samples will be collected and analyzed for concentrations of 5 heavy metals (Pb, Hg, As, Mn, and Al) using inductively coupled plasma mass spectrometry (ICP-MS) analysis. The concentrations of these metals will be correlated with CAP test performance using regression analysis and non-parametric ANOVA (Kruskal-Wallis) analysis will be used to assess differences between children with metal levels above compared to those within the reference range. The proposed work will build upon existing research capacities and collaboration with two major collaborating institutions in Nicaragua by: 1) developing research capabilities and providing instruments that are ideally suited to remote impoverished environments, 2) adapting and training research personnel in database (REDCap) design and implementation, 3) providing a foundation for future comprehensive epidemiological studies through training, 4) mentoring Nicaraguan researchers in advanced research design and methodology, 5) providing additional expertise in specialized areas of interest (e.g. central auditory processing disorders, heavy metal neurotoxicity), 6) facilitating the research partnership between MMO and UNAN-Leon CISTA. This project will provide preliminary data on heavy metal exposure and central auditory test performance that would form the basis for a follow-up grant submission from our Nicaraguan colleagues to address this important environmental health issue.