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: 10816240
• 负责人: Jonathan Douglas Santoro
• 金额: $ 6.25万
• 依托单位: CHILDREN'S HOSPITAL OF LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10816240
• 关键词: Acceleration; Accounting; Active Learning; Address; Age; Architecture; Area; Bioinformatics; Biological Markers; Biometry; Blood Pressure; Blood Vessels; Brain; CCL2 gene; Caring; Cerebrovascular Circulation; Cerebrovascular Disorders; Child; Childhood; Chronic; Clinical Trials; Clinical Trials Design; Cluster Analysis; 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; Etiology; Functional disorder; Funding; Genetic Diseases; Gliosis; Goals; Granulocyte-Macrophage Colony-Stimulating Factor; Head and neck structure; Health; Health Sciences; 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; Predictive Value; Prevalence; Prevention; Program Development; Prospective Studies; Publishing; Regression Analysis; Reproducibility; Research; Research Personnel; Retrospective Studies; Risk; Risk Assessment; Role; 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; biomedical informatics; blood pressure elevation; blood pressure reduction; 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, 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) 博士是一位临床医生科学家，专注于探索血管疾病、 唐氏综合症 (DS) 患者的脑血管疾病 (CeVD) 和炎症。这个五年 受指导的职业发展奖将为他提供基于人口的高级培训和技能 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 独立的研究生涯。概述的提案以 Santoro 博士之前发表的工作为基础 利用 DS、神经发育、血管疾病和脑血管方面的专家组成的指导团队 在他所在机构和其他大型 DS 学术中心对 DS 患者进行炎症性疾病治疗。 研究背景：患有 DS 的人患早期 CeVD 的风险增加，特别是烟雾病综合征， 最初的表现往往是继发于脑血管意外的不可逆的神经损伤。为了 对于 DS 患者，目前尚无有效的方法来评估 CeVD 风险。本次K23职业发展 Santoro 博士之前的工作是建立在 Santoro 博士之前的工作基础上的，他确定了对患有 CeVD 的儿童进行非侵入性筛查的方法 DS。这项研究将前瞻性地评估 DS 患者的血压 (BP)，并随后将其用于 预测症状前 CeVD（目标 1）。接下来，这项研究将比较金标准 CeVD 神经影像 研究各种非侵入性、低成本的生物识别工具，例如重复血压测量、经颅血压测量 多普勒超声和神经认知测试可评估这些措施的内部和预测有效性 CeVD 的预测（目标 2）。由于 DS 患者存在免疫失调，并且 全身炎症特征，我们还将探讨全身和血管炎症生物标志物的作用 在 CeVD 的发展中，目标是确定可能的炎症级联反应 在后续研究中以预防 CeVD 为目标的治疗干预（目标 3）。 职业发展计划：桑托罗博士将完成医疗保健和科学传播方面的课程， 数据分析、临床试验设计和生物医学信息学。该计划还将增强他的能力 生物信息学和神经影像学，并辅以机构讲习班和研讨会。这 体验式学习旨在促进执行任务所需的知识和技能发展 研究并确保培养他向独立研究员过渡的技能。桑托罗博士的 职业发展目标将通过经验丰富且忠诚的人员的密切指导来支持 跨学科团队以及教学、体验和团队学习的结合。该提案和 随后的 R01 提案旨在改善患有 DS 的年轻人的神经护理。