A Social Genomics Model to Explore Loneliness and Systemic Inflammation in an Older Adult Population with Chronic Venous Leg Ulcers

探索患有慢性静脉腿部溃疡的老年人群的孤独感和全身炎症的社会基因组学模型

• 批准号: 10056870
• 负责人: Teresa J Kelechi
• 金额: $ 23.73万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-09 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10056870
• 关键词: Address; Affect; Age; Age-Years; Anti-Inflammatory Agents; Anxiety; Atherosclerosis; Biological; Biological Markers; Biological Response Modifiers; Blood Vessels; Blood specimen; Cardiovascular Diseases; Chronic; Chronic Disease; Clinic; Clinic Visits; Clinical; Cognition; Cytokine Signaling; Data; Development; Diabetes Mellitus; Distress; Elderly; Exhibits; Fatigue; Future; Gene Abnormality; Gene Expression; Gene Family; Genes; Genetic Transcription; Growth Factor; Health Care Costs; Health Status; Hypothalamic structure; IL6 gene; Immune; Individual; Inflammation; Inflammatory; Leg Ulcer; Length; Link; Literature; Loneliness; Longitudinal observational study; Matrix Metalloproteinases; Mediating; Mediation; Mental Depression; Meta-Analysis; Methods; Modeling; Molecular; National Institute of Nursing Research; Nutritional status; Outpatients; Pain; Pathologic Processes; Pathway interactions; Patients; Pattern; Persons; Physiological; Pituitary Gland; Play; Population; Prognostic Marker; Psychoneuroimmunology; Psychosocial Factor; Public Health; Quality of life; Questionnaires; Research; Role; Sleep disturbances; Social isolation; Social support; Symptoms; TGFB1 gene; TNF gene; Time; Ulcer; Up-Regulation; Vascular Endothelial Growth Factors; Venous; Visit; Whole Blood; biological adaptation to stress; biopsychosocial; chronic wound; clinical encounter; cytokine; disability; healing; immunoregulation; improved; link protein; mortality; prospective; psychological stressor; psychological symptom; psychosocial; response; sex; social genomics; social relationships; social stigma; specific biomarkers; stressor; symptom science; telomere; transcriptome sequencing; wound; wound care; wound healing; wound treatment

PROJECT SUMMARY/ABSTRACT In response to PA-17-493, Addressing Chronic Wound Trajectories Through Social Genomics Research (R21), this application seeks to advance social genomics research by exploring psychosocial stressors, symptoms and biomarkers in a chronic wound population. The most common type of chronic wound is a venous leg ulcer (CVLU), which accounts for 70-80% of the 6.5 million wounds currently being treated in the U.S. at health care costs approaching $25 billion. One of the most common psychosocial stressors is loneliness, which affects 68% of individuals with CVLUs, negatively influencing social relationships and reducing quality of life. Unfortunately, psychosocial stressors are rarely assessed or managed during clinical encounters, and may play a predominant role in the chronic, non-healing state. Loneliness has been linked to systemic inflammation through various molecular pathways such as the upregulation of inflammatory genes. Inflammation is also a well-established biological pathway associated with poor healing suggesting inflammation is a common molecular mechanism that underlies both loneliness and poor wound healing. However, the confluence of loneliness and inflammation in a wound population has not been elucidated. Thus, we hypothesize that substantially heightened inflammation is a common molecular mechanism with a distinct profile that underlies both loneliness and poor wound healing in a chronic wound population compared to a wound population without loneliness. In this application, using a social genomics framework guided by the psychoneuroimmunology (PNI) paradigm and the conserved transcriptional response to adversity (CTRA) model, the aims of our prospective observational longitudinal study are to: examine whether psychosocial stressors (i.e., social isolation, social support) and symptoms (i.e., fatigue, pain, depression, anxiety, sleep disturbance, reduced QOL) differ between lonely (L+) and non-lonely (L-) patients with CVLUs using well-validated questionnaires; characterize a biomarker (chemotaxic factors, growth factors, vascular damage and immune regulators) profile common to L+ and CLVU using well-established RNA sequencing and PCR methods for whole blood samples; and, explore whether age and sex/psychological stressors and symptoms indicate potential moderation/mediation of the effect of loneliness on the biomarker profile, over a 3-month study period, collecting data at 3 time points during wound care. We will also explore demographic and other variables such as age (60 – 74, ≥75 years), sex, chronic illnesses, cognition, health status, functional activity, stigma, nutritional status, length of time to heal (healing trajectory), and wound treatment type across the 3 time points. The long-term objective of this research to better understand molecular mechanisms common to loneliness and inflammation towards development of a biopsychosocial prognostic indicator of healing potential in persons with chronic wounds.

项目总结/摘要 针对PA-17-493，通过社会基因组学研究解决慢性伤口轨迹（R21）， 这项申请旨在通过探索心理社会压力源、症状和 慢性创伤人群中的生物标志物。最常见的慢性伤口类型是下肢静脉溃疡 （CVLU），占目前在美国医疗保健中治疗的650万伤口的70-80% 成本接近250亿美元。最常见的心理社会压力源之一是孤独，影响68%的人。 CVLU患者的生活质量下降，对社会关系产生负面影响，并降低生活质量。 不幸的是，社会心理压力很少被评估或管理在临床遇到，并可能发挥作用， 在慢性不愈合状态中起主要作用。孤独症与全身炎症有关 通过各种分子途径，如炎症基因的上调。炎症也是一种 与不良愈合相关的成熟生物学途径表明炎症是常见的 孤独和伤口愈合不良的分子机制。然而， 创伤群体中的孤独和炎症尚未阐明。因此，我们假设， 显著升高的炎症是一种常见的分子机制， 在慢性伤口人群中，孤独和伤口愈合不良的特征 与没有孤独感的受伤人群相比。在这个应用中，使用社会基因组学 由心理神经免疫学（PNI）范式和保守的转录反应指导的框架 在逆境（CTRA）模型中，我们的前瞻性观察性纵向研究的目的是： 心理社会压力源（即，社会孤立，社会支持）和症状（即，疲劳，疼痛， 抑郁、焦虑、睡眠障碍、生活质量下降）在孤独（L+）和非孤独（L-）患者之间存在差异 使用经过充分验证的问卷进行CVLU;表征生物标志物（趋化因子、生长 因素，血管损伤和免疫调节剂）的配置文件共同L+和CLVU使用完善的 全血样本的RNA测序和PCR方法;以及，探索年龄和性别/心理 压力源和症状表明孤独对生物标志物的影响可能是适度的/中介的 在3个月的研究期间，收集伤口护理期间3个时间点的数据。我们还将探索 人口统计学和其他变量，如年龄（60 - 74岁，≥75岁）、性别、慢性疾病、认知、健康 状态、功能活动、耻辱、营养状况、愈合时间长度（愈合轨迹）和伤口 3个时间点的治疗类型。这项研究的长期目标是更好地了解 孤独和炎症共同的分子机制对生物心理社会发展的影响 慢性创伤患者愈合潜力的预后指标。