Non-invasive biometric screening for cerebrovascular disorders in persons with Down syndrome.

唐氏综合症患者脑血管疾病的无创生物识别筛查。

• 批准号: 10353415
• 负责人: Jonathan Douglas Santoro
• 金额: $ 18.53万
• 依托单位: CHILDREN'S HOSPITAL OF LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-17 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10353415
• 关键词: Accounting; Active Learning; Address; Age; Architecture; Area; Bioinformatics; Biological Markers; Biometry; Blood Pressure; Blood Vessels; CCL2 gene; Caring; Cerebrovascular Circulation; Cerebrovascular Disorders; Child; Childhood; Chronic; Clinical Trials; Clinical Trials Design; Communication; Competence; Data; Data Analyses; Deposition; Development; Development Plans; Diagnosis; Disease; Disease Pathway; Down Syndrome; Early Diagnosis; Early Intervention; Early identification; Edema; Educational workshop; Ensure; Epidemiology; Etiology; Functional disorder; Funding; Genetic Diseases; Gliosis; Goals; Gold; Granulocyte-Macrophage Colony-Stimulating Factor; Head and neck structure; Health; Healthcare; Height; Hemosiderin; Home; Hypertension; Hypotension; Image; Immune; Incidence; Individual; Infant; Inflammation; Inflammatory; Institution; Interferon Type II; Interleukin-6; Investigation; K-Series Research Career Programs; Knowledge; Learning; Link; Location; Los Angeles; Magnetic Resonance Imaging; Measurement; Measures; Mentors; Mentorship; Metabolic dysfunction; Modality; Morbidity - disease rate; Moyamoya Disease; Neck; Neurocognitive; Neurologic; Neurologic Symptoms; PGF gene; Patients; Persons; Physicians; Positioning Attribute; Prevalence; Prevention; Program Development; Prospective Studies; Publishing; Regression Analysis; Reproducibility; Research; Research Personnel; Retrospective Studies; Risk; Role; Science; Scientist; Screening procedure; Secondary to; Standardization; Stenosis; Stroke; TNF gene; Techniques; Therapeutic Intervention; Time; Training; Transcranial Doppler Ultrasonography; Ultrasonography; United States; United States National Institutes of Health; Vascular Cell Adhesion Molecule-1; Vascular Diseases; Vascular Endothelial Growth Factors; Weight; Work; aged; base; biomedical informatics; blood pressure elevation; blood pressure reduction; brain magnetic resonance imaging; career; career development; cerebrovascular; chronic inflammatory disease; cohort; cost; design; early screening; experience; feasibility research; improved; interleukin-22; mortality; neurocognitive test; neurodevelopment; neuroimaging; population based; predictive marker; prevent; prospective; response; screening; sex; skills; systemic inflammatory response; tool; vascular inflammation

ABSTRACT: Dr. Jonathan Santoro is a clinician-scientist focused on exploring the interface between vascular disease, cerebrovascular disease (CeVD) and inflammation in persons with Down syndrome (DS). This five-year mentored career development award will provide him with advanced training and skills in population-based data analysis, biostatistics, neuroimaging, and clinical trials development to ensure a successful transition to an independent research career. The outlined proposal builds on previously published work by Dr. Santoro and leverages a mentorship team of experts in DS, neurodevelopment, vascular disease, and cerebrovascular- inflammatory disorders in persons with DS at his home institution and other large academic DS centers. Research Context: Persons with DS have an increased risk of early CeVD, specifically moyamoya syndrome, and the initial presentation is often irreversible neurologic insult secondary to cerebrovascular accident. For persons with DS, there exists no validated means of assessing risk for CeVD. This K23 career development builds on previous work by Dr. Santoro who identified non-invasive ways to screen for CeVD in children with DS. This study will prospectively asses blood pressure (BP) in persons with DS and subsequently use this to predict pre-symptomatic CeVD (Aim 1). Next, this study will compare gold standard CeVD neuroimaging studies to various non-invasive, low-cost, biometric tools such as repeated BP measurements, transcranial Doppler ultrasound and neurocognitive testing to assess internal and predictive validity of these measures in the prediction of CeVD (Aim 2). As persons with DS are established to have immune dysregulation and systemic inflammatory profiles, we will also explore the role of systemic and vascular inflammatory biomarkers in the development of CeVD with the goal of identifying contributory inflammatory cascades that could be targeted with therapeutic interventions geared towards preventing CeVD in subsequent studies (Aim 3). Career Development Plan: Dr. Santoro will complete coursework in healthcare and science communication, data analysis, epidemiology, clinical trial design and biomedical informatics. This plan also will strengthen his competence in both bioinformatics and neuroimaging and be supplemented by institutional workshops and seminars. This experiential learning is designed to promote knowledge and skillset development needed to both execute his research and ensure that skills are developed for his transition to an independent researcher. Dr. Santoro’s career development goals will be supported through close mentorship by an experienced and committed interdisciplinary team and a combination of didactic, experiential, and team-based learning. This proposal and subsequent R01 proposals seek to improve the neurologic care of young persons with DS.

抽象的： 乔纳森·桑托罗（Jonathan Santoro）博士是一位临床科学家，致力于探索血管疾病之间的界面， 唐氏综合症患者（DS）的脑血管疾病（CEV）和炎症。这个五年 指导的职业发展奖将为他提供基于人群的高级培训和技能 数据分析，生物统计学，神经影像学和临床试验开发，以确保成功过渡到 独立的研究职业。概述的提案是建立在Santoro博士和 利用DS，神经发育，血管疾病和脑血管的心态团队 在其家庭机构和其他大型学术DS中心，患有DS的人的炎症障碍。 研究环境：DS患者患有早期CEV的风险，特别是Moyamoya综合征， 最初的表现通常是脑血管事故继发的不可逆神经损伤。为了 具有DS的人，没有评估CEV风险的验证手段。这个K23职业发展 基于Santoro博士以前的工作，他确定了非侵入性的方法来筛选患有CEV的儿童 DS。这项研究可能会在患有DS的患者中评估血压（BP），然后将其用于 预测症状前CEV（AIM 1）。接下来，本研究将比较金标准CEVD神经影像学 研究各种非侵入性，低成本的生物识别工具，例如重复的BP测量，经颅 多普勒超声和神经认知测试，以评估这些措施的内部和预测有效性 CEVD的预测（AIM 2）。随着DS患者的免疫失调，并且 全身性炎症曲线，我们还将探讨系统性和血管炎症生物标志物的作用 在CEV的发展中，目的是确定可能是 采用旨在在随后的研究中预防CEV的治疗干预措施（AIM 3）。 职业发展计划：Santoro博士将完成医疗保健和科学传播课程， 数据分析，流行病学，临床试验设计和生物医学信息。这个计划也将加强他的 生物信息学和神经影像学的能力，并由机构讲习班补充 半人物。这种经验学习旨在促进所需的知识和技能发展 两者都执行他的研究，并确保发展为过渡到独立研究人员的技能。 Santoro博士的职业发展目标将由经验丰富的和 犯了在跨学科团队，并结合了教学，专家和基于团队的学习。这 提案和随后的R01提案寻求改善DS年轻人的神经护理。