Acute exercise tolerance among Veterans with Gulf War Illness

此职业发展奖（CDA-2）应用程序的目的是为了方便博士。 从慢性多症状疾病（CMI）的新研究者转变为独立的翻译 VA医疗保健系统的调查员。本CDA-2的具体重点是研究有氧运动 不容忍的流行和衰弱的CMI称为海湾战争疾病。林德海默博士是一位 心理生理学家，具有运动科学领域的背景，目前是博士后研究员 在退伍军人事务部新泽西医疗保健系统的战争相关疾病和伤害研究中心。他和一个 与他的共同导师Dane Cook和Michael Falvo博士一起进行了一项多中心的病理学Merit Review研究， GWI的生理机制。该CDA-2将使Lindheimer博士获得以下方面的额外技能：（1）临床 试验和生物统计学，（2）免疫测定数据的分析和解释，以及（3）临床练习 生理测试另一个培训目标是让林德海默博士继续开发神经成像技术， 他在博士后奖学金培训期间获得的技能。神经成像将不被用作 在拟议的研究结果的措施，但将是一个重要组成部分，随后的优点审查 在本CDA-2的第5年申请。 研究计划的总体目标是为制定运动处方提供关键信息 这对患有GWI的退伍军人来说是可以忍受的。为此，开发了一种新颖的创新研究设计 测量有氧运动强度与普遍现象之间的剂量-反应关系 影响CMI人群的因素（例如，海湾战争疾病，肌痛性脑脊髓炎/慢性疲劳综合征， 纤维肌痛）称为运动后不适（PEM）。虽然很明显，有氧运动可以诱导 PEM，引发PEM的运动的具体特征不是。受试者内、随机、对照， 交叉研究将测试轻度、中度和剧烈运动对症状、行为和 GWI退伍军人样本中PEM的生物学指标（n=40）。 我们的中心假设是，运动和肥胖之间存在着剂量依赖性关系。 强度和PEM，表现为：GWI症状严重程度增加（目的1），疼痛增加 敏感性（目标1），认知能力下降（目标1），促炎性和 调节性细胞因子（即，IL-6、IL-8、IL-10、TNF-α）（目的2），体力活动行为减少（目的3），以及 增加久坐行为（目标3）。将使用经验证的问卷来测量GWI症状。 疼痛敏感性将通过心理-物理程序进行测量，用于确定对疼痛的感知反应。 一系列的热刺激。认知表现将使用计算机化版本的Paced 听觉序列加法任务。促炎性细胞因子将通过多细胞因子阵列使用免疫组织化学法测量。 电化学发光平台身体活动和久坐行为将通过以下方式进行测量： 加速度测量法参与者将完成一个初步的熟悉实验室访问，然后是四个额外的 实验性访问。目标1和2中的所有措施将在20分钟之前和之后立即实施 有氧自行车运动目标3措施将在每次实验性访视后进行一周。 经过一周的体力活动监测和一周的恢复（总共两周）， 参加者将返回实验室完成随后的实验参观。 博士Lindheimer将利用这项研究的结果来制定一个基于证据的运动处方， 预防患有GWI的退伍军人中PEM的症状、行为和生物学后果。使用数据 从这项研究中收集的技能和经验，从严格的职业发展计划中获得 Lindheimer博士和他的指导团队已经开发出了这种基于证据的练习的有效性， 处方将在Merit Review调查中进行测试，重点是更广泛的退伍军人与CMI。

The purpose of this Career Development Award (CDA-2) application is to facilitate Dr. Jacob Lindheimer's transition from a new investigator of chronic, multi-symptom illnesses (CMI) into an independent translational investigator in the VA Healthcare System. The specific focus of this CDA-2 is on studying aerobic exercise intolerance in a prevalent and debilitating CMI known as Gulf War Illness. Dr. Lindheimer is an integrative psycho-physiologist with a background in the field of exercise science and is currently a Post-Doctoral Fellow at the War Related Illness and Injury Study Center of the VA New Jersey Healthcare System. He works closely with his co-mentors, Drs. Dane Cook and Michael Falvo, on a multi-site Merit Review study of patho- physiological mechanisms in GWI. This CDA-2 will allow Dr. Lindheimer to obtain additional skills in (1) clinical trials and biostatistics, (2) analysis and interpretation of immunological assay data, and (3) clinical exercise physiology testing. An additional training goal is for Dr. Lindheimer to continue developing the neuroimaging skills that he acquired during his post-doctoral fellowship training. Neuroimaging will not be used as an outcome measure in the proposed research, but will be an essential component of a subsequent Merit Review application in Year 5 of this CDA-2. The overall goal of the research plan is to provide critical information for developing an exercise prescription that is tolerable for Veterans with GWI. To that end, a novel and innovative study design has been developed to measure the dose-response relationship between aerobic exercise intensity and a pervasive phenomenon that affects CMI populations (e.g., Gulf War Illness, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, Fibromyalgia) known as post-exertion malaise (PEM). Although it is clear that aerobic exercise can induce PEM, the specific features of exercise that elicit PEM are not. A within-subjects, randomized, controlled, crossover study will test the effect of light- moderate- and vigorous exercise on symptomatic, behavioral and biological indices of PEM in a sample of Veterans with GWI (n=40). Our central hypothesis is that is that there will be a dose-dependent, relationship between exercise intensity and PEM, which is manifested by: increases in GWI symptom severity (Aim 1), increases in pain sensitivity (Aim 1), decreases in cognitive performance (Aim 1), up-regulation of pro-inflammatory and regulatory cytokines (i.e., IL-6, IL-8, IL-10, TNF-α) (Aim 2), decreases in physical activity behavior (Aim 3), and increases in sedentary behavior (Aim 3). Validated questionnaires will be used to measure GWI symptoms. Pain sensitivity will be measured with psycho-physical procedures used to determine perceptual responses to a range of thermal stimuli. Cognitive performance will be measured with a computerized version of the Paced Auditory Serial Addition Task. Pro-inflammatory cytokines will be measured by multi-cytokine array using an electrochemiluminescence platform. Physical activity and sedentary behavior will be measured via accelerometry. Participants will complete an initial familiarization lab visit, followed by four additional experimental visits. All measures in Aims 1 and 2 will be administered immediately before and after 20 minutes of aerobic cycling exercise. Aim 3 measures will take place for one-week following each experimental visit. Following one week of physical activity monitoring and an additional week of recovery (two weeks total), participants will return to the lab to complete subsequent experimental visits. Dr. Lindheimer will use the findings from this study to develop an evidence based exercise prescription for preventing symptomatic, behavioral and biological consequences of PEM in Veterans with GWI. Using the data collected from this study and the skills and experiences obtained from the rigorous career development plan that Dr. Lindheimer and his mentoring team have developed, the efficacy of this evidence based exercise prescription will be tested in a Merit Review investigation focused on a broader range of Veterans with CMIs.