CSRD Research Career Scientist Award Application

CSRD研究职业科学家奖申请

• 批准号: 10491686
• 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/10491686
• 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)是一种复杂且知之甚少的疾病 疲劳的以疲劳、疼痛和认知功能问题为特征的对于退伍军人来说，这些疾病是 统称为海湾战争疾病(GWI)，影响约250,000名海湾战争退伍军人(GV)(25%-35% 1991年GV人口)。近50%的GV寻求退伍军人临床护理，近40%的GV患有残疾 补偿。到目前为止，这些症状的原因尚不清楚，因此没有有效的方法。 治疗方法是可用的。此外，最近的证据表明，最近冲突中的退伍军人，如 持久行动和伊拉克自由也在经历CMI。 我的研究的总体重点是确定维持慢性多发性骨髓瘤的机制。 症状疾病(CMI)--如肌痛性脑脊髓炎/慢性疲劳综合征(ME/CFS)， 纤维肌痛(FM)和GWI--职业目标是改善部署人员的健康和生活质量 退伍军人。我的研究采用了多种最先进的技术，使我们能够测试中央、自主 每个来过我实验室的退伍军人的心肺和免疫系统。因此，我的研究表明， 患有CMI的GV和平民的多个生理系统都出现了功能障碍。此外，功能障碍 在运动挑战(即，运动后)后，这些系统内的症状被放大和加重 劳损[PEM])，为他们的研究提供了一个可控的模型。因此，我的一个核心假设是 研究表明，跨多个生理系统的功能障碍相互作用，产生并维持 GWI的症状，这种功能障碍最好通过挑战生理系统和测试如何 他们相互作用。来自我的实验室的数据显示，患有慢性肌肉骨骼疼痛的GV减少了白色 与健康的GV相比，剧烈运动使他们对疼痛更加敏感。然而， 我的实验室还报告说，体育锻炼对这两种疾病都有潜在的保护作用。 缺陷和这些疾病的症状。这些结果表明，急性和慢性运动可能会对 对GV健康的不同影响，开发非药物疗法的重要信息 被用来安全地治疗GWI。 我目前由退伍军人事务部赞助的研究通过比较GV和GV来直接测试我们的多系统假说 在休息和急性运动挑战后，为跨多个生理系统的健康GV提供GWI；我们 使用高级统计方法测试多个系统之间的交互是否显著解释 GWI的症状。利用我的实验室和我的合作者的专业知识，我们测试了：中枢神经 使用结构和功能磁共振成像的系统调节；2)使用 脑血流测量的脑多谱勒方法；3)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测量；以及4)症状测量 使用经过验证的工具来评估疼痛、疲劳和认知。 总而言之，我的研究产生了重要的数据，有助于了解 GWI，并通过这样做为未来的治疗试验创造了生理靶点。我的研究目标是 方案直接符合退伍军人事务部的使命，以照顾那些有 我为这个国家服务过，因此我相信我完全有资格获得CSR&D研究职业科学家奖。