CSRD Research Career Scientist Award Application

CSRD研究职业科学家奖申请

• 批准号: 10231863
• 负责人: DANE B. COOK
• 金额: --
• 依托单位: WM S. MIDDLETON MEMORIAL VETERANS HOSP
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10231863
• 关键词: Acute; Affect; Aging; Alzheimer' s Disease; Autonomic nervous system; Award; Behavioral; Blood; Blood Pressure; Brain; Brain imaging; Cardiopulmonary; Caring; Cerebrovascular Circulation; Chronic; Chronic Fatigue Syndrome; Cognition; Cognitive; Collaborations; Complex; Conflict (Psychology); Country; Data; Diffusion Magnetic Resonance Imaging; Discipline; Disease; Endocrine; Exercise; Exertion; Fatigue; Fibromyalgia; Financial compensation; Freedom; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Future; Gene Expression; Goals; Gulf War; Gulf War veteran; Health; Image; Immune; Immune system; Immunity; Immunologic Tests; International; Journals; Leadership; Lymphocyte; Malaise; Measurement; Measures; Medicine; Mentors; Metabolic; Methodology; Methods; Mission; Modeling; Nervous System Physiology; Neuraxis; Neurology; Neurosciences; Nonpharmacologic Therapy; PF4 Gene; Pain; Pain Research; Paper; Persian Gulf Syndrome; Physical activity; Physiological; Plasma; Proteomics; Psychophysiology; Publications; Publishing; Quality of life; Regulation; Reporting; Research; Rest; Rheumatology; Sampling; Science; Scientist; Sensory; Services; Source; Sports; Sports Medicine; Statistical Methods; Stimulus; Stress; Structure; Students; Symptoms; System; Technology; Testing; United States Department of Veterans Affairs; Veterans; Visit; Work; active lifestyle; biological systems; blood flow measurement; blood oxygen level dependent; brain behavior; cardiopulmonary system; career; chronic musculoskeletal pain; chronic pain; clinical care; cognitive function; cognitive task; cooking; cost; disability; efficacious treatment; experience; imaging modality; improved; indexing; insight; instrument; interdisciplinary approach; metabolomics; military veteran; neuroimaging; operation; programs; protective effect; psychobiology; response; tool; treatment trial; white matter

Chronic multi-symptom illnesses (CMI) are complex and poorly understood diseases principally characterized by fatigue, pain, and problems with cognitive function. For Veterans, these diseases are collectively referred to as Gulf War Illnesses (GWI) and affect ~250,000 Gulf War Veterans (GVs) (25-35% of the 1991 GV population). Nearly 50% of GVs seek VA clinical care, and nearly 40% receive disability compensation. To date, the causes of these symptoms are not known, and as a result, no efficacious treatments are available. Moreover, recent evidence suggests that Veterans of more recent conflicts, such as Operations Enduring and Iraqi Freedom, are also experiencing CMI. The general focus of my research is to determine the mechanisms that act to maintain chronic multi- symptom illnesses (CMI) – such as myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), and GWI – with a career goal of improving the health and quality of life of deployed Veterans. My research employs multiple state-of-art technologies that allow us to test the central, autonomic, cardiopulmonary, and immune systems of each Veteran that visits my lab. As a result, my research has shown that multiple physiological systems are dysfunctional in both GVs and civilians with CMI. Moreover, dysfunction within these systems is magnified and symptoms are exacerbated following an exercise challenge (i.e., post- exertion malaise [PEM]), providing a controllable model for their study. Thus, a central hypothesis of my research is that dysfunction across multiple physiological systems interacts to produce and maintain the symptoms of GWI, and this dysfunction is best studied by challenging physiological systems and testing how they interact. Data from my lab has shown that GVs with chronic musculoskeletal pain have reduced white matter health and that acute exercise makes them more sensitive to pain compared to healthy GVs. However, my lab has also reported that being physically active has a potential protective effect against both the identified deficits and the symptoms of these diseases. These results suggest that acute and chronic exercise may have differential effects on GV health, important information for developing non-pharmacological therapies that can be used to safely treat GWI. My current VA-sponsored research directly tests our multisystem hypothesis by comparing GVs with GWI to healthy GVs across multiple physiological systems, at rest and following acute exercise challenge; we use advanced statistical methods to test whether interactions among multiple systems significantly explain symptoms of GWI. Capitalizing on the expertise of my lab and my collaborators, we test: 1) central nervous system regulation using structural and functional magnetic resonance imaging; 2) autonomic regulation using brain doppler methods for cerebral blood flow measurement; 3) immune and metabolic regulation using measures of gene expression, metabolomics, and proteomics from blood; and 4) symptoms measurement using validated instruments to assess pain, fatigue, and cognition. In summary, my research has produced important data that helps to inform the pathophysiology of GWI, and by doing so has created physiological targets for future treatment trials. The goals of my research program are directly in line with the mission of the Department of Veterans Affairs, to care for those who have served this country, and thus I believe that I am well-qualified for a CSR&D Research Career Scientist Award.

慢性多症状疾病（CMI）很复杂，并且主要了解疾病主要是 具有疲劳，疼痛和认知功能问题的特征。对于退伍军人，这些疾病是 统称为海湾战争疾病（GWI），影响约25万，海湾退伍军人（GVS）（占25-35％ 1991年的GV人口）。将近50％的GV寻求VA临床护理，近40％接受残疾 赔偿。迄今为止，这些符号的原因尚不清楚，因此没有高效 可以治疗。此外，最近的证据表明，最近发生的冲突的退伍军人，例如 持久的运营和伊拉克自由也正在经历CMI。 我的研究的一般重点是确定维持慢性多多种作用的机制 症状疾病（CMI） - 例如肌电脑脊髓炎 /慢性疲劳综合征（ME / CFS）， 纤维肌痛（FM）和GWI - 其职业目标是改善部署的健康和生活质量 退伍军人。我的研究员工多种最先进的技术，使我们能够测试中心，自主教， 访问我的实验室的每个退伍军人的心肺和免疫系统。结果，我的研究表明 在使用CMI的GV和平民中，多个物理系统均功能失调。此外，功能障碍 在这些系统中，在锻炼挑战之后会放大这些系统，并加剧符号（即 劳累不适[PEM]），为其研究提供了受控模型。那是我的核心假设 研究是，多个物理系统之间的功能障碍与生产和维护 GWI的症状以及这种功能障碍最好通过挑战生理系统和测试如何研究 他们互动。我实验室的数据表明，患有慢性肌肉骨骼疼痛的GV减少了白色 与健康的GV相比，物质健康和急性运动使它们对疼痛更敏感。然而， 我的实验室还报告说，身体活跃具有潜在的保护作用 这些疾病的缺陷和症状。这些结果表明急性和慢性运动可能有 对GV健康的差异影响，为开发非药物疗法的重要信息，可以 被用来安全治疗GWI。 我目前的VA赞助研究直接通过比较GV与 GWI在多个物理系统中，在急性运动挑战之后，在多个物理系统中进行健康的GV； 使用先进的统计方法来测试多个系统之间的相互作用是否明显解释 GWI的症状。利用我的实验室和合作者的专业知识，我们测试：1）中央紧张 使用结构和功能磁共振成像进行系统调节； 2）使用 脑多普勒方法用于脑血流测量； 3）使用的免疫和代谢调节 血液中基因表达，代谢组学和蛋白质组学的度量； 4）符号测量 使用经过验证的仪器来评估疼痛，​​疲劳和认知。 总而言之，我的研究产生了重要的数据，有助于告知 GWI，通过这样做为将来的治疗试验创造了物理目标。我的研究目标 计划直接符合退伍军人事务部的使命，以照顾那些 为这个国家服务，因此我相信我获得了CSR＆D研究职业科学家奖的资格。