Immune Activation and Neurodegeneration in HIV Infection and Heavy Drinking

HIV 感染和酗酒中的免疫激活和神经变性

• 批准号: 10373467
• 负责人: Mollie A Monnig
• 金额: $ 12.76万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-15 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10373467
• 关键词: 3 year old; 3-Dimensional; Acquired Immunodeficiency Syndrome; Acute; Administrative Supplement; Alcohol consumption; Alcoholic beverage heavy drinker; Alcohols; Behavioral; Biological Assay; Biological Markers; Blood; Blood - brain barrier anatomy; Blood Circulation; Brain; CD4 Lymphocyte Count; COVID-19; COVID-19 pandemic; Caring; Cells; Characteristics; Child; Chronic; Clinical; Clinical Investigator; Clinical Research; Collaborations; Collection; Contracts; Control Groups; Data; Data Analyses; Data Collection; Dose; Employment; Environment; Family; Fiber; Functional disorder; Funding; Goals; Guidelines; HIV; HIV Infections; HIV Seronegativity; HIV Seropositivity; Heavy Drinking; Home; Image; Immune; Immune response; Immune system; Immunologic Markers; Immunology procedure; Individual; Infiltration; Inflammation; Inflammatory; Injury; Intestinal permeability; Knowledge; Laboratories; Light; Link; Magnetic Resonance Imaging; Mediating; Mentored Patient-Oriented Research Career Development Award; Mentors; Modeling; National Institute on Alcohol Abuse and Alcoholism; Nerve Degeneration; Neurosciences Research; Outcome; Paper; Parents; Parietal; Participant; Peripheral; Persons; Placebos; Plasma; Procedures; Process; Production; Protocols documentation; Public Health; Publications; Publishing; Randomized; Reporting; Research; Research Activity; Research Personnel; Research Project Grants; Research Training; Risk; Risk Factors; Safety; Saliva; Sampling; Scientist; Social Distance; Solid; Structure; Sum; Testing; Time; TimeLine; Training; Training Activity; Urine; Viral Load result; Viral Proteins; Woman; alcohol effect; alcohol research; alcohol use disorder; biobehavior; career; career development; caregiving; cognitive testing; comorbidity; coronavirus disease; cytokine; design; drinking; gut bacteria; gut-brain axis; immune activation; interest; laboratory experiment; medication nonadherence; microbial; monocyte; mortality; negative affect; neuroimaging; neurotoxic; pandemic disease; payment; public health relevance; relating to nervous system; research data dissemination; response; secondary analysis; skills; symposium; translational neuroscience; white matter; white matter damage

PROJECT ABSTRACT This administrative supplement is submitted in response to NOT-OD-21-052 on “Requesting Extensions for Early Career Scientists Whose Career Trajectories Have Been Significantly Impacted by COVID-19.” Dr. Mollie Monnig’s K23 award was nearing the end of Year 4 in March 2020 when the COVID pandemic caused a nationwide shutdown. Prior to the shutdown, research and training activities were on track for timely completion. However, negative impacts of COVID have delayed the completion of research projects and training goals. The first major impact was disruption of laboratory alcohol research from March 2020-January 2021. The K23 study is an intensive lab experiment that must be conducted in person due to controlled alcohol administration and collection of biospecimens (breath, blood, saliva, and urine samples). The study cannot be adapted to remote administration in a safe or meaningful way. Resumption of data collection required creation of new safety protocols and extensive adaptation of in-person procedures (e.g., blood collection, cognitive testing, alcohol administration) to follow social distancing and biosafety guidelines. Employment contracts with research staff were honored, yet staff were not able to complete primary research duties for which they were hired. Payment of research staff during lab downtime significantly diminished the funds now available to complete data collection and to perform biomarker assays on Aim 4 outcomes. Some supplies (e.g., vacutainers) were expired and had to be disposed of. In addition to lab downtime, the PI Dr. Monnig was unable to engage fully in career development activities such as networking, grantwriting, research dissemination, and didactics due to the need to care for her two young children (under 3 years of age) at home. Dr. Monnig’s family lost access to childcare for 5 months in 2020 due to the pandemic. Thus, funds are requested to offset expenses for loss of RA effort, supplies, and PI effort. The proposed extension will allow Dr. Monnig to fully achieve K23 aims by completing data collection and analysis. Although Dr. Monnig submitted two R01 proposals while under lockdown in March and July of 2020, inability to finish K23 research on the original timeline weakened these proposals due to incomplete preliminary data. Similarly, although Dr. Monnig has published or submitted primary papers for Aims 1 and 2, research barriers and lack of childcare delayed the primary publications for Aims 3 and 4. There is clear evidence that women and junior scientists have been more severely affected by negative impacts of COVID on research, especially when they have major caregiving responsibilities.1-4 In sum, the proposed extension will support Dr. Monnig’s transition to independent investigator via completion of K23 aims, as well as key career development activities (collaborations, funding applications, publications, and networking). Dr. Monnig’s primary mentor, Dr. Peter Monti, and secondary mentor, Dr. Ronald Cohen, are very committed to the successful completion of the K23 award and will remain highly involved in Dr. Monnig’s career development, training, and research activities.

项目摘要 本行政补充文件是根据关于“请求延长 早期职业科学家的职业轨迹受到COVID-19的重大影响。莫丽博士 Monnig的K23奖项于2020年3月接近第四年年底，当时COVID大流行导致 全国范围内关闭。在关闭之前，研究和培训活动正在及时进行， 建成然而，COVID的负面影响延迟了研究项目的完成， 培训目标。第一个重大影响是从2020年3月至2020年1月中断实验室酒精研究 2021. K23研究是一项密集的实验室实验，由于酒精控制，必须亲自进行 给药和收集生物样本（呼吸、血液、唾液和尿液样本）。这项研究不能 适合于以安全或有意义的方式进行远程管理。恢复数据收集需要创建 新的安全协议和广泛的适应性的人的程序（例如，血液采集，认知 测试，酒精管理），以遵循社会距离和生物安全准则。雇用合同 研究人员受到表彰，但工作人员无法完成他们的主要研究职责， 录用了在实验室停工期间支付研究人员的费用大大减少了现在可用于 完成数据收集并对目标4结果进行生物标志物测定。一些供应品（例如， 真空采血管）已过期，必须处理。除了实验室停机时间，PI Monnig博士 无法充分参与职业发展活动，如建立网络、撰写赠款、研究 由于她需要照顾两个年幼的孩子（3岁以下）， 回家Monnig博士的家庭在2020年因疫情而失去了5个月的托儿服务。因此，资金 要求补偿RA工作、用品和PI工作损失的费用。拟议的延期将允许博士。 Monnig通过完成数据收集和分析，全面实现K23目标。尽管莫尼格博士提交了 两个R 01提案在2020年3月和7月处于封锁状态，无法完成K23研究， 由于初步数据不完整，最初的时间轴削弱了这些建议。同样，尽管Monnig博士 发表或提交了关于目标1和2的主要论文，研究障碍和缺乏儿童保育的问题被推迟 目标3和4的主要出版物。有明确的证据表明，女性和年轻科学家一直在 更严重地受到COVID对研究的负面影响，特别是当他们有重大 1 -4总之，拟议的延期将支持Monnig博士过渡到 通过完成K23目标以及关键职业发展活动，担任独立调查员 （合作，资金申请，出版物和网络）。蒙尼格博士的主要导师彼得博士 Monti和第二导师罗纳德科恩博士非常致力于成功完成K23 他将继续积极参与Monnig博士的职业发展、培训和研究活动。