Minimizing mass panic with saliva tests for radiation exposure

描述(申请人提供)：历史告诉我们，在城市地区发生核袭击/事故的紧急恐慌中，数万至数十万惊慌失措的人要求接受暴露评估，很可能会使我们的紧急护理系统不堪重负，从而危及对那些生命紧迫的人的有效分流和治疗。一种对惊慌失措的人群进行暴露筛查的方法，使我们能够迅速安抚未暴露的人，并只保留那些需要立即干预的人，这将有助于减轻我们应急系统的负担。在这项提案中，我们将应用一种蛋白质组生物标记物发现管道，我们已经证明该管道可以有效地发现唾液中的辐射响应蛋白。我们将开发酶联免疫吸附分析(ELISA；一种传统的蛋白质诊断格式)来检测唾液辐射生物标记物。这些ELISA将根据它们的剂量和激活时间进行表征。在这项提议结束时，这些检测可以转换为辐射暴露的护理点诊断，可以在紧急设施储存和分发，并由潜在受害者通过舔诊断试纸进行自我管理。由于许多人不会受到感染，这将极大地减少需要卫生保健系统进行更密集干预的人数。具体目标1：在公认的辐射暴露犬模型中使用基因组和蛋白质组技术确定候选唾液辐射生物标记物特定目标2：验证在犬模型中发现的唾液辐射生物标记物也存在于全身照射(TBI)后的人类唾液中特定目标3：开发可储存的、类似于非处方怀孕试验的ELISA，用于1-3个唾液辐射生物标记物，并对在TBI前后获得的人和犬的唾液样本进行表征历史告诉我们，在城市地区发生核攻击/事故的直接恐慌中，数以万计的惊慌失措的人要求接受暴露评估，这可能会使我们的紧急护理系统不堪重负，从而危及对那些生命垂危的人的有效分流和治疗。一种对惊慌失措的人群进行暴露筛查的方法，使我们能够迅速安抚未暴露的人，并只保留那些需要立即干预的人，这将有助于减轻我们应急系统的负担。在这项提案中，将开发一种基于唾液的辐射暴露测试，可以在急救设施分发，潜在受害者通过舔诊断试纸自行进行。由于许多人不会受到感染，这将极大地减少需要卫生保健系统进行更密集干预的人数。

DESCRIPTION (provided by applicant): History tells us that amidst the immediate panic of a nuclear attack/accident in an urban area, tens-to-hundreds of thousands of panicked people demanding to be evaluated for exposure will likely overwhelm our emergency care system and consequently jeopardize effective triage and treatment of those whose lives are imminently in danger. A method for screening the panicked masses for exposure, allowing us to rapidly reassure the unexposed and to retain only those individuals for whom immediate intervention is required, would help alleviate the burden on our emergency systems. In this proposal, we will apply a proteomic biomarker discovery pipeline that we have already shown to be effective to discover radiation-responsive proteins in saliva. We will develop Enzyme-Linked ImmunoSorbent assays (ELISAs; a conventional protein diagnostics format) for detection of salivary radiation biomarkers. These ELISAs will be characterized with respect to their dose and time course of activation. By the end of this proposal, these assays can be converted into a point-of- care diagnostic for radiation exposure that can be stockpiled and distributed at emergency facilities and self- administered by potential victims by licking a diagnostic test strip. Because many individuals will not have been exposed, this will dramatically decrease the number of individuals requiring more intensive intervention from the health care system. Specific Aim 1: Identify candidate salivary radiation biomarkers using genomic and proteomic technologies in the well-established canine model of radiation exposure Specific Aim 2: Verify that salivary radiation biomarkers discovered in the canine model are also present in human saliva post total body irradiation (TBI) Specific Aim 3: Develop stockpile-able Enzyme-Linked ImmunoSorbent Assays (ELISAs), similar to the over- the-counter pregnancy test, for 1-3 salivary radiation biomarkers and characterize these assays on human and canine saliva samples procured pre- and post-TBI History tells us that amidst the immediate panic of a nuclear attack/accident in an urban area, tens-to-hundreds of thousands of panicked people demanding to be evaluated for exposure will likely overwhelm our emergency care system and consequently jeopardize effective triage and treatment of those whose lives are imminently in danger. A method for screening the panicked masses for exposure, allowing us to rapidly reassure the unexposed and to retain only those individuals for whom immediate intervention is required, would help alleviate the burden on our emergency systems. In this proposal, will develop a saliva-based test for exposure to radiation that can be distributed at emergency facilities and self-administered by potential victims by licking a diagnostic test strip. Because many individuals will not have been exposed, this will dramatically decrease the number of individuals requiring more intensive intervention from the health care system.