Novel biomarkers as a clinical tool for excessive alcohol use screening

项目摘要 过量饮酒（EAU）是美国可预防的伤害和死亡的主要原因之一。 EAU的及时干预和有效治疗依赖于早期发现过量饮酒，通常 通过临床筛选。EAU早期症状和体征的识别延迟， 有机会中断酒精暴露的积累，并导致次优的护理结果， 与酒精有关的健康问题。迫切需要提高警惕并采取行动， 为有EAU风险的患者提供咨询。利用人类转录组沿着蛋白质组学方法，我们 已经发现了与EAU病理生理学潜在相关的标志物。我们发现激活 酒精（sCd 14、sCD 163和尿新蝶呤）对单核细胞的影响和对CD 4+滤泡T细胞的抑制 （sCD 40）与饮酒水平密切相关。我们相信，借助现代 分析技术，这些新的生物标志物可以用作新的基于机制的基础。 筛选策略，显着提高了诊断性能。为了验证这个假设， 我们将追求以下目标：具体目标1。确定这些新血清的诊断潜力 和EAU的尿标志物;特异性目标2。构建代表EAU的筛选评分 使用现代半参数回归技术确定个体受试者的概率和标记 #36825;目标1、具体目标3。验证筛选模型。如果成功实施， 该项目可能会彻底改变EAU筛查和诊断的实践。小说的认同 标记物还提供了科学依据，以更好地了解潜在的健康后遗症的机制， EAU。

Project Summary Excessive alcohol use (EAU) is one the leading causes of preventable injury and death in the Unites States. Timely intervention and effective treatment of EAU relies on early detection of excessive drinking, usually through clinical screening. Delayed recognition of early signs and symptoms of EAU would lead to missed opportunities to interrupt the accumulation of alcohol exposure and result in suboptimal care outcomes in alcohol-related health conditions. There is an urgent need for increased vigilance and action to identify and to counsel patients that are at-risk for EAU. Using human transcriptome along with proteomic approaches, we have uncovered markers that are potentially linked to the EAU pathophysiology. We found that activation of monocytes by alcohol (sCd14, sCD163, and urine neopterin) and suppression of CD4+ follicular T cells (sCD40) are strongly associated with levels of alcohol consumption. We believe that with the aid of modern analytical techniques, these novel biomarkers could be used as basis for a new mechanistic-based screening strategy that have significantly improved the diagnostic performance. To test this hypothesis, we will pursue the following aims: Specific Aim 1. To ascertain the diagnostic potential of these novel serum and urinary markers for EAU; Specific Aim 2. To construct a screening score that represents the EAU probability of individual subject by using modern semiparametric regression techniques and markers identified in Aim#1; and Specific Aim 3. To validate the screening model. If successfully implemented, results from this project could revolutionize the practice of EAU screening and diagnosis. The identification of the novel markers also provides a scientific basis to better understand the mechanisms underlying the health sequelae of EAU.