Minimizing mass panic with saliva tests for radiation exposure

描述（由申请人提供）：历史告诉我们，在城市地区发生核袭击/核事故的即时恐慌中，数万至数十万恐慌的人要求进行暴露评估，这可能会压倒我们的紧急护理系统，从而危及对生命处于迫在眉睫危险中的人的有效分类和治疗。一种筛选恐慌群众的暴露方法，使我们能够迅速使未暴露的人安心，并只保留那些需要立即干预的人，将有助于减轻我们应急系统的负担。在本提案中，我们将应用蛋白质组学生物标志物发现管道，我们已经证明它可以有效地发现唾液中的辐射反应蛋白。我们将开发酶联免疫吸附测定法（elisa；一种传统的蛋白质诊断格式）用于检测唾液辐射生物标志物。这些elisa将根据其剂量和激活时间进行表征。到本提案结束时，这些检测可以转化为辐射暴露的即时诊断，可以储存和分发到应急设施，并由潜在的受害者通过舔诊断测试条进行自我管理。由于许多人不会受到感染，这将大大减少需要卫生保健系统进行更密集干预的人数。特定目标1：在已建立的犬类辐射暴露模型中，利用基因组学和蛋白质组学技术确定候选的唾液辐射生物标志物。特定目标2：验证在犬类模型中发现的唾液辐射生物标志物在全身照射（TBI）后也存在于人类唾液中。开发可储存的酶联免疫吸附测定法（elisa），类似于非药品妊娠试验，用于检测1-3种唾液辐射生物标志物，并在创伤性脑损伤前后采集的人类和犬唾液样本中对这些测定进行表征。历史告诉我们，在城市地区发生核攻击/事故的即时恐慌中，成千上万的恐慌的人们要求对暴露程度进行评估，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处于迫在眉睫危险中的人的有效分类和治疗。一种筛选恐慌群众的暴露方法，使我们能够迅速使未暴露的人安心，并只保留那些需要立即干预的人，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，可在紧急设施分发，并由潜在受害者通过舔诊断测试条自行进行。由于许多人不会受到感染，这将大大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.