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

项目摘要/摘要 响应PA-17-493，通过社会基因组研究解决慢性伤口轨迹(R21)， 该应用程序寻求通过探索心理社会应激源、症状和 慢性伤口人群中的生物标记物。最常见的慢性伤口是静脉性腿部溃疡。 (CVLU)，占美国目前在医疗保健部门接受治疗的650万个伤口的70%-80% 成本接近250亿美元。孤独是最常见的心理社会压力源之一，它影响着68%的人 对患有CVLU的个人产生负面影响，并降低生活质量。 不幸的是，心理社会应激源很少在临床接触中被评估或管理，并且可能起作用。 在慢性的、不可治愈的状态中起主导作用。孤独被认为与全身炎症有关 通过各种分子途径，如炎症基因的上调。炎症也是一种 已建立的与愈合不良相关的生物途径表明炎症是一种常见的 孤独和伤口愈合不良的分子机制。然而，两国的汇合 创伤人群中的孤独感和炎症尚未阐明。因此，我们假设 炎症显著加重是一种常见的分子机制，具有明显的 慢性创面人群中孤独和创面愈合不良的基础 与没有孤独的受伤人群相比。在这个应用程序中，使用了社会基因组学 心理神经免疫学(PNI)范式指导的框架和保守的转录反应 对于逆境(CTRA)模型，我们的前瞻性观察纵向研究的目的是：检验 心理社会应激源(即社会隔离、社会支持)和症状(即疲劳、疼痛、 孤独者(L+)与非孤独者(L-)的抑郁、焦虑、睡眠障碍、生活质量降低 使用经过充分验证的问卷进行CVLU；表征生物标记物(趋化因子、生长 因子、血管损伤和免疫调节剂)与L+和慢性阻塞性肺疾病的共同特征 全血样本的RNA测序和聚合酶链式反应方法；以及探索年龄和性别/心理 应激源和症状表明孤独对生物标记物的影响具有潜在的缓和/调节作用 在3个月的研究期间，在伤口护理期间的3个时间点收集数据。我们还将探索 人口和其他变量，如年龄(60-74岁，≥75岁)、性别、慢性病、认知、健康 状态、功能活动、污名、营养状态、愈合时间(愈合轨迹)和伤口 治疗类型跨越3个时间点。这项研究的长期目标是更好地理解 孤独和炎症共同的分子机制对生物心理社会发展的影响 慢性创面患者愈合潜力的预后指标。

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.