Neurometabolic profile of tobacco smoking in HIV-infected Individuals

HIV 感染者吸烟的神经代谢特征

• 批准号: 10797405
• 负责人: Muhammad G Saleh
• 金额: $ 24.9万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10797405
• 关键词: Affect; Age; Aminobutyric Acids; Antioxidants; Aspartate; Basal Ganglia; Basic Science; Biochemical Process; Brain; Brain Injuries; Brain region; Cell membrane; Chemicals; Choline; Chronic; Cigarette; Clinical; Clinical Data; Clinical Research; Clinical assessments; Cognitive deficits; Complement; Complex; Development; Disease; Drug usage; Economic Burden; General Population; Glutamates; Glutathione; Goals; HIV; HIV Infections; Health; Human; Impaired cognition; Impulsivity; Individual; Investigation; Learning; Lipids; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Mentors; Metabolic Marker; Metabolism; Methodology; Methods; Mission; Morbidity - disease rate; Morphologic artifacts; Motion; N-acetylaspartate; N-acetylaspartylglutamate; National Institute of Drug Abuse; Neurocognitive Deficit; Neuromodulator; Neuronal Injury; Neurons; Neurotransmitters; Nicotine; Noise; Oxidative Stress; Parietal; Participant; Patients; Persons; Phase; Pilot Projects; Prevalence; Protocols documentation; Protons; Psychopathology; Public Health; Reporting; Reproducibility; Research; Research Design; Research Proposals; Scanning; Scientist; Short-Term Memory; Signal Transduction; Smoker; Smoking; Socioeconomic Status; Spectrum Analysis; Standardization; Statistical Methods; System; Techniques; Technology; Tobacco; Tobacco smoking behavior; Training; Vendor; Viral Load result; Work; antiretroviral therapy; ascorbate; brain health; career; cell type; cigarette smoking; clinical application; clinical training; data acquisition; executive function; experience; experimental study; gray matter; improved; in vivo; interest; magnetic field; metabolic abnormality assessment; mortality; neurobiological mechanism; neurochemistry; neuroimaging; neuroinflammation; neuroregulation; neurotransmission; novel; patient population; prospective; reconstruction; sex; skills; tobacco smokers; tool; training opportunity; white matter

Project Summary Tobacco smoking is a serious public health concern and is 2 to 3 times more prevalent among HIV-infected individuals than the general population. Smoking reduces the efficacy of combination antiretroviral therapy and substantially impacts the long-term survival of HIV-infected individuals. Several studies have suggested that chronic tobacco (cigarette) smoking and HIV infection have harmful additive or synergistic effects on the brain, leading to greater psychopathology, impulsivity and cognitive dysfunction. Little is known about the neurochemical profile related to the combined effects of HIV infection and smoking. HERCULES is a novel J- difference-edited magnetic resonance spectroscopy (MRS) technique that can measure up to seven low- concentration brain metabolites (e.g., GABA) with relatively short scan times. However, HERCULES is sensitive to subject motion, which affects both localization accuracy and spectral quality. Both HIV-infected subjects and tobacco smokers have greater impulsivity that might lead to greater subject motion. Therefore, the aims of this project are: 1) K99 phase: the candidate will be mentored in the development of the motion-corrected HERCULES sequence, which will allow robust investigation of these neurometabolites; he will also assess the reproducibility of HERCULES with and without motion correction in seronegative (SN) healthy controls; 2) K99 phase: to learn to conduct a pilot clinical study using the optimized motion-corrected HERCULES to evaluate the neurometabolic profile of HIV-infected individuals or tobacco smokers, compared to SN healthy controls; 3) R00 phase: to measure a comprehensive neurochemical profile in four groups of individuals (SN/tobacco-, HIV+/tobacco-, SN/tobacco+, HIV+/tobacco+), using the motion-corrected HERCULES sequence. Based on the proposed clinical training and didactic courses, the candidate will work with experienced globally recognized experts in the fields of MRS and clinical HIV research to achieve five training goals: (1) develop expertise in research design and clinical assessments of HIV-infected individuals and tobacco smokers; (2) conduct a pilot study to evaluate the independent effects of HIV and tobacco smoking on neurometabolite levels; (3) learn to apply an advanced MRS technique to clinical research, especially in HIV+ individuals and tobacco smokers; and (4) learn to apply advanced statistical methods to analyze complex clinical data from patient populations. The long-term career objective of the candidate is to become an independent scientist with a complete repertoire of skills in MRS methodologies and their clinical applications. The motion-corrected HERCULES can be applied to study metabolic processes in other diseases as well, adding scope and impact to this research proposal, which is also responsive to NIDA’s mission of “strategically supporting and conducting basic and clinical research on drug use (including nicotine), its consequences, and the underlying neurobiological mechanisms involved.”

项目摘要 烟草吸烟是一个严重的公共卫生问题，在感染HIV的人中是2至3倍 个人比普通人群。吸烟降低了抗逆转录病毒疗法的效率 实质上影响了艾滋病毒感染者的长期生存。几项研究表明 慢性烟草（香烟）吸烟和HIV感染对大脑具有有害的添加剂或协同作用， 导致更大的心理病理学，冲动和认知功能障碍。关于 神经化学谱与HIV感染和吸烟的综合作用有关。大力神是一本小说的J- 差异编辑的磁共振光谱（MRS）技术，可以测量多达七个低 - 浓度脑代谢物（例如GABA），扫描时间相对较短。但是，大力神很敏感 主题运动，这会影响本地化精度和光谱质量。均受HIV感染的受试者， 烟草吸烟者的冲动性更大，可能会导致更多的受试者运动。因此，目的 项目为：1）K99阶段：将在运动校正的开发中考虑候选人 大力神序列将允许对这些神经代谢物进行强大的投资；他还将评估 在静脉（SN）健康对照中进行有或没有运动校正的大力神的可重复性； 2）K99 阶段：学会使用优化的运动校正力量进行试验临床研究以评估 与SN健康对照相比，HIV感染的个体或烟草吸烟者的神经代谢概况； 3）R00 阶段：测量四组个体的全面神经化学谱（SN/烟草，， 使用运动校正的大力神序列，HIV+/烟草，SN/烟草+，HIV+/烟草+）。基于 拟议的临床培训和教学课程，候选人将与经验丰富的全球认可 MRS和临床HIV研究领域的专家实现五个培训目标：（1）发展专业知识 对艾滋病毒感染者和烟草吸烟者的研究设计和临床评估； （2）进行飞行员 研究艾滋病毒和烟草吸烟对神经代谢物水平的独立影响； （3）学会 将高级MRS技术应用于临床研究，尤其是在HIV+个体和吸烟者中；和 （4）学会应用高级统计方法来分析患者人群中复杂的临床数据。 候选人的长期职业目标是成为一名独立科学家 MRS方法及其临床应用的技能。通过运动校正的大力神可以应用于 研究其他疾病中的代谢过程，为这项研究提案增加了范围和影响， 还对NIDA的使命做出了敏感 药物使用（包括尼古丁），其后果以及所涉及的潜在神经生物学机制。”