Early life fluoride exposure, neurodevelopment and childhood sleep patterns

项目总结 我是一名临床心理学家，对了解环境暴露对神经内分泌的作用感兴趣。 发展。这项提议的目标是接受培训，以获得继续我的 通过研究儿童氟化物暴露在睡眠模式和褪黑激素产生中的作用，研究儿童的学术生涯。 在这项提议中，我计划与一个具有跨学科专业知识的专家指导团队进行培训，包括 暴露生物学、睡眠障碍、毒理学、流行病学和生物统计学。具体地说，我将在1) 与Manish Arora博士合作的暴露科学2)与Michael Thorpy博士合作的临床睡眠研究，以及3)毒理学 和罗伯特·赖特医生一起。我还将获得流行病学方面的专门知识，并对 与Rosalind Wright、Emily Oken和Kristie Ross博士的儿科睡眠，以及与Chris博士的生物统计 根宁斯。提议的正式课程和与我的导师、顾问和合作者的培训将 使我能够获得成为独立跨学科所需的知识和技能 研究员。此外，这将使我能够实现我成为一名环境保护工作者的长期职业目标 健康科学家，研究环境毒物在睡眠和神经内分泌发育中的作用。 我建议利用生物检疫和收集的措施，包括尿液、唾液、活动数据和自我 据报道，来自现有的预期出生队列的白天疲劳，肥胖规划研究， 成长环境与社会压力研究。我还打算进行一项深入的临床研究 尿氟与青少年睡眠的黄金标准测量之间的关系。这项工作将解决 目标如下：1.测定4-5岁和6-7岁儿童尿氟浓度(CUF) 预测睡眠和醒来时间、睡眠持续时间和睡眠效率(通过加速度计测量)以及白天 晚年的疲劳(通过有效的自我报告问卷测量)；检查唾液是否 6-7年龄褪黑激素节律调节CUF与睡眠模式/日间疲劳的关系 目标1中评估的儿童；3.)确定尿氟水平是否与 青少年睡眠呼吸暂停的生理睡眠参数和症状的评估 蒙特菲奥里医疗中心的唤醒障碍中心。 这项拟议的研究是第一次研究儿童早期接触氟化物是否 预测儿童睡眠模式、白天疲劳或褪黑激素节律的变化。因此，它将推进 通过提供关于可改变的潜在风险的有价值的信息来进行儿科睡眠研究领域 儿科睡眠障碍的因素。它还将有助于通知滴定适当剂量的氟化物 最大限度地提高牙齿健康功效，最大限度地降低风险。我会以具成本效益的方式进行这项研究 利用以前资助的队列中的可用资源。最后，我将把研究和培训翻译成 这项提议将我定位为一名拥有终身教职的独立调查员。

PROJECT SUMMARY I am a clinical psychologist interested in understanding the role of environmental exposures in neuro-endocrine development. The goal of this proposal is to receive training to acquire the skills needed to continue my academic career by examining the role of child fluoride exposure in sleep patterns and melatonin production. In this proposal, I plan to train with an expert mentoring team with transdisciplinary expertise covering exposure biology, sleep disorders, toxicology, epidemiology and biostatistics. Specifically, I will train in 1) exposure science with Dr. Manish Arora 2) clinical sleep research with Dr. Michael Thorpy, and 3) toxicology with Dr. Robert Wright. I will also acquire expertise in epidemiology and the epidemiological assessment of pediatric sleep with Drs. Rosalind Wright, Emily Oken and Kristie Ross, as well as biostatistics with Dr. Chris Gennings. The proposed formal coursework and training with my mentors, advisors and collaborators will enable me to acquire the knowledge and skills necessary to become an independent transdisciplinary researcher. Further, it will enable me to achieve my long-term career goal of becoming an environmental health scientist investigating the role of environmental toxicants in sleep and neuro-endocrine development. I propose to leverage biospecimens and collected measures, including urine, saliva, Actigraphy data, and self- reported daytime fatigue from an existent prospective birth cohort, the Programming Research in Obesity, Growth Environment and Social Stress study. I also aim to conduct an in-depth clinical study examining associations of urine fluoride with gold standard measures of sleep among adolescents. This work will address the following aims: 1.) Determine whether childhood urinary fluoride concentrations (CUF) at 4-5 and 6-7 years predict sleep and wake time, sleep duration and sleep efficiency (measured via accelerometry) and daytime fatigue (measured via a validated self-report questionnaire) at later ages; 2.) Examine whether salivary melatonin rhythms at 6-7 years mediate the association between CUF and sleep patterns/daytime fatigue among children as assessed in Aim 1; 3.) Determine whether urinary fluoride levels are associated with physiological sleep parameters and symptoms of sleep apnea among adolescents assessed at the Sleep- Wake Disorders Center at Montefiore Medical Center. The proposed research represents the first study to examine whether early childhood fluoride exposure predicts changes in childhood sleep patterns, daytime fatigue or melatonin rhythms. As such, it will advance the field of pediatric sleep research by providing valuable information regarding a modifiable potential risk factor for pediatric sleep disturbances. It will also help to inform titration of the appropriate dose of fluoride to maximize dental health efficacy and minimize risk. I will conduct this study in a cost-effective manner by levering available resources from a previously funded cohort. Lastly, I will translate the research and training in this proposal to position myself as an independent investigator with a tenure track faculty position.