Center for Addiction and Disease Risk Exacerbation

项目总结/摘要 物质使用（SU）对慢性疾病的风险、管理、进展和结局产生负面影响， 造成社会经济和种族/民族不平等。2005 - 2007年妇女健康状况的患病率 与那些没有物质滥用障碍（SUD）的患者支持这一论点。此外，风险是 在那些有风险或已经患有慢性疾病的人中加剧，例如患有 艾滋病。虽然SU和疾病之间的联系已经有了很好的记录，但潜在的生理机制 联系知之甚少，主要是因为文献是基于使用横截面的研究， 不允许因果解释的设计。需要使用实验设计的研究， 了解SU与疾病之间的联系机制，并为制定有针对性的预防措施提供信息， 采取干预措施降低风险。我们建议建立一个COBRE成瘾和疾病风险中心 急性加重（CADRE），将研究SU影响疾病的机制，使用以下组合 行为和生理实验室为基础的方法，对几种物质的滥用。干部 由四个主题和技术相关的研究项目（RP），由一个跨学科小组领导， 初级教员。Monnig将研究HIV和酒精对微生物易位标记物的影响， 活化、细胞因子应答、色氨酸降解和炎症的MRI测量。哈斯-科夫勒将 检查催产素作为阿片类药物复吸中OUD靶向压力的潜在药物疗法的初步疗效。 CIOE将研究电子烟对可燃香烟吸烟的影响，吸烟相关心脏疾病的生物标志物， 和肺部健康，以及感染艾滋病毒的吸烟者的致癌物质暴露。阿斯顿研究大麻对 RA疼痛，影响和炎症，并调查大麻对疼痛和影响的影响是否是介导的 通过大麻对炎症生物标志物的影响。一个行政核心将提供组织结构， 最先进的指导，试点计划，支持多样性和健康差异工作，并领导评估。一 临床实验室核心将促进RP和试点项目的目标，并使更广泛的布朗受益 通过提供基础设施和资源，为发展和维持一个多功能的社区服务， 纪律中心。它将通过在以下方面建立联系，最大限度地提高这一COBRE的效率和成本效益： CADRE RP和其他COBREs，并将创建一个中心范围的风险因素数据库， SUD和慢性疾病的发展和进展，提供给CADRE项目负责人（PL）， 其他从事相关研究。PL和试点PL将受益于跨学科的教师导师， 将为研究、出版和拨款准备提供指导。拟议的COBRE的基本原则是 CADRE是创新的跨学科转化研究，在多个层次的分析， 利用共同的资源和学习经验， 新知识，而且也是下一代科学家走向独立的纽带和道路。

Project Summary/Abstract Substance use (SU) negatively affects the risk, management, progression, and outcomes of chronic disease and contributes to socio-economic and racial/ethnic disparities. Prevalence rates of medical conditions among patients with versus those without substance abuse disorders (SUDs) support this thesis. Furthermore, risks are exacerbated among those at risk for or who already have chronic medical conditions, such as people living with HIV. Though linkages between SU and disease are well documented, physiological mechanisms underlying linkages are poorly understood, largely because the literature is based on studies that use cross-sectional designs that do not allow for causal interpretations. Studies using experimental designs are needed to understand mechanisms that link SU and disease and to inform the development of targeted prevention and intervention efforts to reduce risks. We propose to establish a COBRE Center for Addiction and Disease Risk Exacerbation (CADRE) that will investigate mechanisms whereby SU impacts disease, using a combination of behavioral and physiological laboratory-based approaches across several substances of abuse. CADRE consists of four thematically and technically-linked research projects (RPs) led by an interdisciplinary group of junior faculty. Monnig will examine effects of HIV and alcohol on markers of microbial translocation, monosite activation, cytokine response, tryptophan degradation and MRI measures of inflammation. Haass-Koffler will examine the initial efficacy of oxytocin as a potential pharmacotherapy for OUD targeting stress in opioid relapse. Cioe will study effects of e-cigarettes on combustible cigarette smoking, biomarkers of smoking-related cardiac and pulmonary health, and carcinogen exposure in smokers with HIV. Aston examines effects of cannabis on RA pain, affect, and inflammation, and investigates whether effects of cannabis on pain and affect are mediated via effects of cannabis on inflammatory biomarkers. An Administrative Core will provide organizational structure, state-of-the-art mentoring, a pilot program, support diversity and health disparities work, and lead evaluation. A Clinical Laboratory Core will facilitate goals of the RPs and pilot projects, and benefit the broader Brown community by providing infrastructure and resources in the service of developing and sustaining a multi- disciplinary center. It will maximize efficiency and cost-effectiveness of this COBRE by creating linkages between CADRE RPs and other COBREs, and will create a center-wide data base of risk factors associated with development and progression of SUDs and chronic disease, available to CADRE Project Leaders (PLs) and others engaged in relevant research. PLs and pilot PLs will benefit from interdisciplinary faculty mentors who will provide guidance on research, publication, and grant preparation. The basic tenet of the proposed COBRE CADRE is that innovative interdisciplinary translational research, conducted across multiple levels of analysis, and focused on related questions using common resources and learning experiences, can not only contribute new knowledge, but also serves as the nexus and path toward independence for the next generation of scientists.