MACS/WIHS Combined Cohort Study: Cook County Clinical Research Site (CC_CRS) - OAR Sleep Supplement

MACS/WIHS 联合队列研究：库克县临床研究中心 (CC_CRS) - OAR 睡眠补充剂

基本信息

批准号：
10658775
负责人：
Mardge H Cohen
金额：
$ 70.01万
依托单位：
HEKTOEN INSTITUTE FOR MEDICAL RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10658775
关键词：
Address Aging Anti-Inflammatory Agents Atherosclerosis Biological Process Cardiometabolic Disease Catabolism Catecholamines Chronic Circadian Dysregulation Cohort Studies Complex County Data Data Store Disease Enzymes Essential Amino Acids Extrahepatic Foundations Funding Goals HIV HIV therapy High Prevalence Hormones Human body Hydrocortisone Individual Inflammation Inflammatory Infrastructure Interferons Interleukin-6 Intervention Kynurenine Length Link Measures Mediating Melatonin Molecular Moods National Heart, Lung, and Blood Institute Neurotransmitters Participant Pathway interactions Peripheral Persons Plasma Play Process Property Quality of life Reporting Research Personnel Research Priority Risk Sampling Serotonin Sleep Sleep disturbances Stress TNF gene Testing Tryptophan Tryptophan 2,3 Dioxygenase Tryptophanase Viral Viral Proteins Woman Wrist actigraphy antiretroviral therapy biological sex cardiometabolic risk cardiometabolism circadian clinical research site cohort comorbidity cooking cytokine depressive symptoms disorder risk early onset immune activation insight men multidisciplinary neurotoxic novel poor sleep sex sleep quality

项目摘要

ABSTRACT The objective of this supplement application is to investigate targeted kynurenine (KYN) pathway metabolites as molecular mechanisms by which objectively measured habitual sleep and circadian disruption increase risk for HIV-associated cardiometabolic disease and to determine whether these relationships differ by biological sex and HIV disease status. We will measure targeted KYN pathway metabolites in stored plasma (n=800) from well characterized MACS/WIHS Combined Cohort Study (MWCCS) men who already have habitual sleep measures collected, validated, and systematically scored via one week continuous wrist actigraphy (Philips Respironics Actiwatch Spectrum Plus). There will be no MWCCS participant and field staff burden for this supplement. No study to date has examined KYN pathway activation as a mechanism linking sleep and circadian disruption to HIV-related and inflammatory mediated comorbidities such as cardiometabolic disease in a mixed sex sample nor has this been accomplished with representation across all HIV disease status groups (well and poorly controlled HIV with comparison to uninfected controls). Results will provide novel insights into biological sex and HIV disease status differences in the mechanistic relationships between sleep and circadian disruption, KYN pathway activation, and HIV-associated cardiometabolic disease and provide a strong foundation upon which to test targeted sleep and circadian interventions to reduce risk for HIV- associated comorbidities in men and women aging with HIV.

抽象的该补充应用的目的是研究目标犬尿氨酸 (KYN) 途径代谢物客观测量习惯性睡眠和昼夜节律紊乱的分子机制会增加风险与 HIV 相关的心脏代谢疾病，并确定这些关系是否因生物学而异性别和艾滋病毒疾病状况。我们将测量储存血浆中的目标 KYN 途径代谢物 (n=800) 来自已经有习惯性睡眠的男性的明确特征的 MACS/WIHS 联合队列研究 (MWCCS) 通过一周连续腕部活动记录仪收集、验证和系统评分的测量结果（飞利浦伟康 Actiwatch Spectrum Plus）。 MWCCS 参与者和现场工作人员不会因此承担任何负担补充。迄今为止，还没有研究检验 KYN 通路激活作为连接睡眠和睡眠的机制。昼夜节律紊乱导致艾滋病相关疾病和炎症介导的合并症，例如心脏代谢疾病在混合性别样本中也未能实现所有艾滋病毒疾病状态的代表性组（与未感染对照相比，艾滋病毒控制良好和较差）。结果将提供新颖的深入了解生物性别和艾滋病毒疾病状况在睡眠之间的机械关系差异和昼夜节律紊乱、KYN 通路激活和 HIV 相关心脏代谢疾病，并提供为测试有针对性的睡眠和昼夜节律干预措施以降低艾滋病毒风险奠定了坚实的基础老年男性和女性感染艾滋病毒的相关合并症。