Project 2: Parkinsonism and Metal Exposures Among Welders

项目2，这将是UW SBRP的新项目，是一项关于金属作为 专业焊工中帕金森症(PS)风险、严重程度和进展的决定因素。 先前的流行病学和实验研究表明， 锰(Mn)和其他金属，单独和组合，以及PS。研究人群包括 875名威斯康星州造船厂焊工(775名在职，100名退休)和200名非暴露造船厂 以前没有焊接接触史的工人参加了正在进行的NEIHS资助的R01(ES013743； 共同调查者：H.Checkoway，N.Seixas)。这项拟议研究的新特点将 改进暴露评估，以生成特定金属的定量水平，并重复 PS相关运动功能纵向改变的神经学检查。的科学目标 该项目是：1)评估锰和其他金属暴露与PS风险之间的剂量-反应关系 和严重性；2)检验这些金属暴露与PS进展相关的假设；3) 确定PS蛋白质组生物标记物的预测关系，如项目3(张博士)所示 PS风险、严重程度和进展；4)测试患有PS的锰和其他金属的剂量-反应关系 蛋白质组生物标志物图谱作为临床前疾病的指标。为了实现这些目标，我们将履行 运动功能的重复标准化神经学检查(统一帕金森病评定量表 马达第3款[UPDRS3])尽可能多的学习科目的招生考试后3年 注册(约75%)。此外，我们将与项目3合作，收集血浆样本用于检测 已被证实与PS密切相关的蛋白质组学，样本为150名选定的受试者 根据基线UPDRS3(‘正常’，交界性PS，可能/明确PS)。潜在的数据 重要的混杂因素，特别是吸烟和接触杀虫剂，将通过 问卷调查。这个项目有很大的潜力来量化金属对神经的影响程度， 是广泛存在的环境污染物，因此可能有助于疾病预防战略。

Project 2, which will be new to the UW SBRP, is an epidemiologic investigation of the roles of metals as determinants of the risk, severity, and progression of parkinsonism (PS) among professional welders. Previous epidemiologic and experimental research has demonstrated very plausible links between manganese (Mn) and other metals, individually and in combination, and PS. The study population includes 875 Wisconsin shipyard welders (775 actively employed, 100 retired) and 200 non-exposed shipyard workers with no welding exposure history previously enrolled in an ongoing NEIHS-funded R01 (ES013743; PI: B. Racette; Co-investigators: H. Checkoway, N. Seixas). The new features of this proposed study will be the refinement of exposure assessment to generate quantitative metal-specific levels, and repeated neurological examinations of longitudinal change of PS-related motor function. The scientific objectives of the project are to: 1) estimate dose-response relations between Mn and other metal exposures and PS risk and severity; 2) test the hypothesis that these metal exposures are associated with PS progression; 3) determine the predictive relations of PS proteomic biomarkers, characterized in Project 3 (Dr. Zhang), with PS risk, severity, and progression; 4) test dose-response relations for Mn and other metals with PS proteomic biomarker profiles as indicators of preclinical disease. To achieve these objects, we will perform repeated standardized neurological exams of motor function (Unified Parkinson's Disease Rating Scale Motor Subsection 3 [UPDRS3]) 3 years after enrollment exams for as many study subjects as can be enrolled (~75%). Addionally, in collaboration with Project 3, we will collect plasma samples for assays of proteomics that have been validated as strongly associated with PS for a sample of 150 subjects selected according to baseline UPDRS3 ('normal', borderline PS, probable/definite PS). Data on potentially important confounding factors, especially cigarette smoking and pesticide exposure, will be obtained by questionnaire. This project has great potential to quantify the extent of neurological effects of metals, which are widespread environmental contaminants, and thus could contribute to disease prevention strategies.