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: 9335838
• 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/9335838
• 关键词: 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; Industrialization; 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; South African; 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 coaching; presynaptic; programs; public health relevance; putamen; student mentoring; tissue biomarkers

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的这种续约基于过去五年中实质性的科学和指导进步。从科学上讲，研究人员进行了影响的人类临床流行病学，成像和病理研究，研究了锰（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，因为它既是必不可少的痕量元素又是已建立的神经毒性。这种更新的科学目的提供了与该应用程序主题一致的MN组织中MN沉积与MN暴露工人的生物标志物之间的关键联系。对这些关系和人类MRI信号强度的生物学的更好理解将提供基本信息，以告知对MN健康影响的未来研究。 研究人员建议利用与南非同事的长期关系，从已故的MN矿工那里收集神经病理学（脑）和其他组织，以研究MN暴露，先进的定量MRI金属序列和组织MN/FE MN/FE浓度之间的相互关系。这项研究将告知他们目前在南非MN矿工中对MN暴露焊工和未来研究的研究。此外，它将提供一个难得的机会来研究大脑和其他暴露受试者其他组织中的金属沉积，以开发和验证生物标志物以进行MN暴露。在过去的五年中，候选人在其神经退行性的环境流行病学实验室以及研究偏头痛，自闭症，中风，肌肉骨骼疾病以及物理治疗/康复的学员中指导了许多学员。 K24提供的受保护的指导时间导致了三项KL2和三项K23赠款，授予了我的学员，众多的基金会培训补助金以及30多个出版物。指导计划中概述的活动是他指导职业发展的逻辑下一步，将有两个关键组成部分。首先，候选人将在华盛顿大学KL2计划中扮演更突出的指导角色，包括基于同伴入学方法制定赠款写作计划。 其次，他将担任维特沃特斯兰大学的国际导师，在那里他将协助指导公共卫生学生并教授NIH Grant写作课程。