Early life fluoride exposure, neurodevelopment and childhood sleep patterns

项目摘要 我是一名临床心理学家，对了解环境暴露在神经内分泌中的作用感兴趣。 发展本提案的目标是接受培训，以获得继续我的工作所需的技能。 通过研究儿童氟暴露在睡眠模式和褪黑激素产生中的作用，对学术生涯进行了研究。 在本建议书中，我计划与具有跨学科专业知识的专家指导团队一起进行培训， 暴露生物学、睡眠障碍、毒理学、流行病学和生物统计学。具体来说，我将在1） 与Manish Arora博士的接触科学2）与Michael Thorpy博士的临床睡眠研究，以及3）毒理学 罗伯特·赖特博士我还将获得流行病学和流行病学评估方面的专门知识， Rosalind Wright、艾米丽Oken和Kristie Ross博士的儿科睡眠研究，以及Chris博士的生物统计学 詹宁斯建议的正式课程和培训与我的导师，顾问和合作者将 使我能够获得必要的知识和技能，成为独立的跨学科 研究员此外，它将使我能够实现我的长期职业目标，成为一名环保工作者。 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。 我建议利用生物标本和收集的测量，包括尿液，唾液，活动记录数据，和自我- 据报道，从现有的前瞻性出生队列，肥胖规划研究， 成长环境与社会压力研究。我还打算进行深入的临床研究， 尿氟与青少年睡眠金标准测量的关系这项工作将解决 目标如下：1.）确定4-5岁和6-7岁儿童尿氟浓度（CUF） 预测睡眠和觉醒时间，睡眠持续时间和睡眠效率（通过加速度计测量）以及白天 疲劳（通过有效的自我报告问卷测量）在以后的年龄; 2.）检查唾液是否 6-7岁时的褪黑激素节律介导了CUF与睡眠模式/日间疲劳之间的关联 目标1中评估的儿童中; 3.）确定尿氟水平是否与 睡眠呼吸暂停综合征患者的睡眠参数和症状 蒙特菲奥里医疗中心的清醒障碍中心。 这项拟议中的研究代表了第一项研究， 预测儿童睡眠模式、白天疲劳或褪黑激素节律的变化。因此， 儿科睡眠研究领域，提供关于可改变的潜在风险的有价值的信息 儿童睡眠障碍的因素。它也将有助于告知滴定的适当剂量的氟化物， 最大限度地提高牙齿健康功效，并将风险降至最低。我将以符合成本效益的方式进行这项研究， 勒韦林现有资源从以前资助的队列。最后，我将把研究和培训转化为 这个建议，定位自己作为一个独立的调查员与终身教职的立场。

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.