Epidemiology and Biomarkers of Parkinsonism in Welders

焊工帕金森病的流行病学和生物标志物

• 批准号: 8925883
• 负责人: Brad A Racette
• 金额: $ 16.72万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8925883
• 关键词: African; Astrocytes; Autistic Disorder; Award; Biological Markers; Biology; Brain; Brain region; Cell Count; Characteristics; Clinical; Complex; Corpus striatum structure; Data; Deposition; Educational process of instructing; Environmental Epidemiology; Epidemiology; Evolution; Exposure to; Foundations; Functional disorder; Funding; Future; Globus Pallidus; Grant; Hair; Health; High Prevalence; Human; Image; Inductively Coupled Plasma Mass Spectrometry; Institution; International; Iron; Laboratories; Link; Lung; Magnetic Resonance Imaging; Manganese; Measures; Mentors; Metals; Microglia; Migraine; Mining; Musculoskeletal Diseases; Nerve Degeneration; Neurons; Neurotoxins; Occupational Exposure; Parkinson Disease; Parkinsonian Disorders; Pathology; Pathway interactions; Pharmacology; Phenotype; Physical therapy; Public Health Students; Publications; Rehabilitation therapy; Relaxation; Research; Research Personnel; Resolution; Role; Signal Transduction; South Africa; Sternum; Stroke; Structure of nail of toe; Time; Tissues; Tooth structure; Trace Elements; Training; United States National Institutes of Health; Universities; Washington; Writing; base; bone; brain tissue; career; contrast imaging; density; disorder risk; graduate student; indexing; neuroinflammation; neuropathology; neurotoxic; neurotoxicity; peer; presynaptic; programs; public health relevance; putamen

DESCRIPTION (provided by applicant) This renewal of K24ES017765 builds on substantial scientific and mentoring progress made in the last five years. Scientifically, the investigators have conducted impactful human clinical epidemiological, imaging, and pathology studies investigating the neurotoxic effects of manganese (Mn) exposure. Manganese (Mn) is a metal with complex pharmacology due to its role as both an essential trace element and an established neurotoxicant. The scientific aims of this renewal provide a critical link between Mn deposition in tissue and biomarkers in Mn- exposed workers, consistent with the theme of this application. A better understanding of these relationships and the biology of the MRI signal intensity in humans will provide essential information to inform future studies on the health effects of Mn. The investigators propose to leverage a long-standing relationship with our colleagues in South Africa to collect neuropathologic (brain) and other tissue from deceased Mn miners to investigate the inter- relationship between Mn exposure, state-of-the-art quantitative MRI metal sequences, and tissue Mn/Fe concentrations. This study will inform their currently funded research in Mn-exposed welders and future studies in South African Mn miners. In addition, it will provide a rare opportunity to investigate metal deposition in brain and other tissues in Mn-exposed subjects in order to develop and validate biomarkers for Mn exposure. Over the last five years, the candidate has mentored numerous trainees in his neurodegenerative environmental epidemiology laboratory as well as trainees studying migraine, autism, stroke, musculoskeletal disorders, and physical therapy/rehabilitation. The protected mentoring time afforded by the K24 has resulted in three KL2 and three K23 grants awarded to my trainees, numerous foundation training grants, and over 30 publications. The activities outlined in the mentoring plan are the logical next step in the evolution of his mentoring career and will have two key components. First, the candidate will take on a more prominent mentoring role in the Washington University KL2 program, including developing a grant writing program based upon a peer-mentoring approach. Second, he will serve as an international mentor at the University of the Witwatersrand, where he will assist in mentoring public health students and teach a course on NIH grant writing.

描述（由申请人提供） K24ES017765 的更新建立在过去五年中取得的实质性科学和指导进展的基础上。从科学角度来看，研究人员进行了有影响力的人类临床流行病学、影像学和病理学研究，调查锰 (Mn) 暴露的神经毒性作用。锰 (Mn) 是一种具有复杂药理学的金属，因为它既是必需的微量元素，又是一种既定的神经毒剂。这一更新的科学目标提供了组织中的锰沉积与接触锰的工人的生物标志物之间的关键联系，这与本申请的主题一致。更好地了解这些关系以及人类 MRI 信号强度的生物学特性将为未来有关锰对健康影响的研究提供重要信息。 研究人员建议利用与南非同事的长期合作关系，从已故的锰矿工身上收集神经病理学（大脑）和其他组织，以研究锰暴露与最先进的定量 MRI 金属序列之间的相互关系。和组织 Mn/Fe 浓度。这项研究将为他们目前资助的接触锰焊工的研究和未来对南非锰矿工的研究提供信息。此外，它将提供一个难得的机会来研究锰暴露受试者大脑和其他组织中的金属沉积，以开发和验证锰暴露的生物标志物。在过去的五年里，这位候选人在他的神经退行性环境流行病学实验室指导了众多学员，以及研究偏头痛、自闭症、中风、肌肉骨骼疾病和物理治疗/康复的学员。 K24 提供的受保护的指导时间使我的学员获得了三项 KL2 和三项 K23 补助金、大量的基础培训补助金和 30 多篇出版物。指导计划中概述的活动是他指导职业发展中合乎逻辑的下一步，并将包含两个关键组成部分。首先，候选人将在华盛顿大学 KL2 项目中发挥更重要的指导作用，包括开发基于同行指导方法的资助写作项目。 其次，他将担任威特沃特斯兰德大学的国际导师，协助指导公共卫生学生并教授 NIH 拨款写作课程。