Journal of Clinical and Translational Science最新文献

{"title":"177 Placing Participant Experiences at the Center of Improving Research by Empowering the Participant Voice","authors":"Rhonda Kost, Ranee Chatterjee, Ann Dozier, Daniel Ford, Joseph Andrews, Nancy Green, Paul A. Harris, Alex Cheng","doi":"10.1017/cts.2024.168","DOIUrl":"https://doi.org/10.1017/cts.2024.168","url":null,"abstract":"OBJECTIVES/GOALS: Empowering the Participant Voice (EPV) is a 6-CTSA Rockefeller-led collaboration to developcustom REDCap infrastructure to collect participant feedback using the validated Research Participant Perception Survey (RPPS), demonstrate its value in use cases, and disseminate it for broad adoption. METHODS/STUDY POPULATION: The EPV team developed data and survey implementation standards, and specifications for the dashboard and multi-lingual RPPS/REDCap project XML file. The VUMC built a custom At-a-Glance Dashboard external module that displays Top Box scores (percent best answer), with conditional formatting to aid analysis, and response/completion rates. Results populate site dashboards, and aggregate to a multi-site dashboard for benchmarking. Results can be filtered by participant/study characteristics. Sites developed individual use cases, leveraging local infrastructure, initiatives and stakeholder input. Infrastructure and guides were designed for dissemination through public websites. RESULTS/ANTICIPATED RESULTS: Five sites sent 23,797surveys via email, patient portal or SMS. 4,133 (19%) participants diverse in age, race, and ethnicity, returned responses. Sites analyzed their data and acted on selected findings, improving recruitment, communication and feeling valued. Aggregate scores for feeling listened to and respected were hight (>90%%); scores for feeling prepared by the consent process were lower (57-77%) and require action. Some groups experiences were better than others. Sites differed significantly in some scores. Dissemination of EPV is underway. Infrastructure and guides are downloadable free of charge, with advice from the EPV team. In 2023, a sixth site began piloting a lower literacy survey version and syncing data to the consortium dashboard. DISCUSSION/SIGNIFICANCE: The EPV RPPS/REDCap infrastructure enabled sites to collect participant feedback, identify actionable findings and benchmark with peers. Stakeholders and collaborators designed and tested local initiatives to increase responses and diversity, address disparities, and discover better practices.","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"60 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"137 Systematic Development of a Multidisciplinary Online Training Program in Healthcare Delivery Science","authors":"Allison Orechwa, Amytis Towfighi","doi":"10.1017/cts.2024.133","DOIUrl":"https://doi.org/10.1017/cts.2024.133","url":null,"abstract":"OBJECTIVES/GOALS: We created an online, competency-based training program for Healthcare Delivery Science (HDS) that incorporates a wide range of disciplines and best educational practices. METHODS/STUDY POPULATION: In collaboration with a curriculum design expert and thirteen content experts from multiple schools and departments, we reviewed and adapted a published set of competencies for learning health system researchers. We followed educational best practices to collaboratively create learning objectives, aligned content with the objectives, and created quiz questions that addressed the objectives. After recording the coursework and building the program in a learning management system, we tested, evaluated, and revised the courses. RESULTS/ANTICIPATED RESULTS: The systematic approach resulted in a novel set of eight online courses: Introduction to Healthcare Delivery Science, Research Methods, Dissemination & Implementation Science, Behavioral Economics, Leadership & Management, Quality Improvement, Systems Engineering, and Multi-Stakeholder Engagement. The courses are applicable to learners from diverse fields, including medicine, public health, pharmacy, engineering, health system administration, and translational science. Students can earn digital badges for individual courses and a certificate of completion for the entire set of courses. DISCUSSION/SIGNIFICANCE: Compared to previously available offerings, the new training program offers a more comprehensive view of this important field. Next, we plan to develop additional courses and create a Masters program that includes synchronous learning and a complementary experiential component for hands-on application of HDS principles.","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"46 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"247 Virtual community and partner-engaged panels - We can do them, but should we?","authors":"Lesli Skolarus, Tamara Sutton, Darius Tandon, Josefina Serrato","doi":"10.1017/cts.2024.227","DOIUrl":"https://doi.org/10.1017/cts.2024.227","url":null,"abstract":"OBJECTIVES/GOALS: We describe the transition of ShAred Resource Panels (ShARPs) within the Center for Community Health (CCH) at Northwestern University’s Clinical and Translational Sciences (NUCATS) Institute to virtual sessions and explore ongoing practices. METHODS/STUDY POPULATION: Restrictions placed during the COVID-19 pandemic led to changes in community-engaged health equity research, such as the transition of community and partner-engaged panels from in-person to virtual. ShARPs have occurred since December 2015. The model includes research team members, community members, community co-facilitator, and CCH staff. These custom panels bring together 8-10 community members familiar with a research topic or community of focus, offering feedback on adaptations that can improve research relevance and feasibility. Until the COVID-19 pandemic, all ShARPs were conducted in person. From March 2020 to January 2023, panels occurred virtually. From 2023, the option of virtual or in-person ShARPs has been available. Count data and informal interview data were reviewed. RESULTS/ANTICIPATED RESULTS: The number of ShARPs peaked in 2019 and has remained stable. The first virtual ShARP occurred on April 22, 2020, and all subsequent sessions have been virtual. As of October 2023, 6 ShARPs have occurred, with no research teams pursuing an in-person session despite its availability. Participants described virtual ShARPs as convenient and accessible. Academic teams cited concern about low community member participation should they opt for an in-person session. DISCUSSION/SIGNIFICANCE: It is feasible to conduct ShARPs virtually and is the current preferred modality. Whether virtual ShARPs enhance, neutralize, or detract from the effectiveness of the session is unknown and guides our future work. More research is needed, including discussion, and learning from our CTSA colleagues.","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"11 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"61 A Multifaceted Approach to Improving Fish Farming in Kenya’s Lake Victoria Region","authors":"Kathryn Fiorella, Eric Teplitz, Rodman Getchell, Grace E. Gonzalez","doi":"10.1017/cts.2024.67","DOIUrl":"https://doi.org/10.1017/cts.2024.67","url":null,"abstract":"OBJECTIVES/GOALS: This project adopts a multifaceted approach to improving aquaculture management practices in Kenya’s Lake Victoria region by identifying fish pathogens, measuring algal toxin levels in commonly consumed fish, surveying fish farming practices, and educating the public. METHODS/STUDY POPULATION: Limited existing data on the state of floating cage culture in Kenya influenced our decision to begin this portion of the project with a brief literature review of potential Nile tilapia pathogens. Databases were screened for mention of disease in either wild or caged Nile tilapia, with emphasis given to those in Lake Victoria. Results were compiled into a spreadsheet and analyzed for frequently occurring pathogens. The next portion involved creating an interview style survey to assess current cage culture management practices in the region. Editing was done to ensure questions remained unbiased, non-leading, culturally sensitive, multilingual and relevant to the situation. Data went through a quality control screening and analysis was conducted through the R programming language. RESULTS/ANTICIPATED RESULTS: Beginning with mortality, of the 93 farms surveyed, data analysis revealed that there is a higher probability that farms will have a mortality of approximately 20%, over the course of a production cycle. For biosecurity and fish health practices, data shows that 97% of farms do not disinfect scooping nets or other fish handling materials when moving from one cage to another. During the 2022-2023 production cycle, 44% of farms experienced fish kills of over 50 fish. 73% of the 93 farms do not contact any organization when a fish kill occurs. In a qualitative answer, it also appears that many farm workers dispose of their dead fish within the lake, feed it to livestock or dogs, or eat it. Algae blooms have been experienced at 80% of the farms surveyed and 43% of farms say they have seen fish gasping at the surface for air. DISCUSSION/SIGNIFICANCE: While farms are implementing good management practices in the areas of cage design, stocking, and feeding practices, there is room for improvement in fish health, biosecurity, and managing algal blooms. The findings provide insight into the areas that should be considered when taking action to improve the welfare of the region.","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"25 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"98 The Crosstalk between Mitochondrial Dysfunction and Neurodevelopmental Outcomes in Preterm Infants with Pain/Stress in the NICU","authors":"Tingting Zhao, Xiaolin Chang, Subrata Biswas, Jeremy Balsbaugh, Jennifer Liddle, Ming-hui Chen, Adam Matson, Xiaomei Cong","doi":"10.1017/cts.2024.96","DOIUrl":"https://doi.org/10.1017/cts.2024.96","url":null,"abstract":"<p>OBJECTIVES/GOALS: Early life pain/stress impacts infants’ neurodevelopmental outcomes. Mitochondrial dysfunction may interface between infants’ stress and neurodevelopment. The study aims to investigate the associations between pain/stress, proteins associated with mitochondrial dysfunction, and neurobehavioral responses in preterm infants. METHODS/STUDY POPULATION: A prospective cohort study was conducted with 33 preterm infants enrolled between September 2017 and July 2022 at two affiliated NICUs in Hartford and Farmington, CT. Daily pain/stress experienced during NICU was documented. At 36-38 weeks post-menstrual age (PMA), neurobehavioral outcomes were evaluated using the NICU Network Neurobehavioral Scale (NNNS) and buccal swabs for Mass spectrometry-based proteomics analysis. Lasso statistical methods were conducted to study the association between protein abundance and infants’ NNNS summary scores. Multiple linear regression and Gene Ontology (GO) enrichment analyses were performed to examine how clinical characteristics and neurodevelopmental outcomes may be associated with protein levels and underlying molecular pathways. RESULTS/ANTICIPATED RESULTS: During NICU hospitalization, preterm premature rupture of membrane (PPROM) was negatively associated with neurobehavioral outcomes. The protein functions, including leptin receptor binding activity, glutathione disulfide oxidoreductase activity, and response to oxidative stress, lipid metabolism, phosphate, and proton transmembrane transporter activity, were negatively associated with neurobehavioral outcomes. In contrast, cytoskeletal regulation, epithelial barrier, and protection function were found to be positively associated with neurodevelopmental outcomes. In addition, mitochondrial dysfunction-related proteins (SPRR2A, PAIP1, S100A3, MT-CO2, PiC, GLRX, PHB2, and BNIPL-2, ABLIM1, UNC45A, Keratins, MUC1, and CYB5B) were found to be associated with neurobehavioral outcomes. DISCUSSION/SIGNIFICANCE: Mitochondrial dysfunction-related proteins were observed to be associated with early life pain/stress and neurodevelopmental outcomes in infants. Buccal proteins could be used to predict potential neurobehavioral outcomes. In addition, individualized skin integrity protection should be provided to preterm infants during their NICU stay.</p>","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"61 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"203 Assessing social determinants of health and psychosocial factors critical to sustaining recovery among pregnant and parenting women with opioid use disorder","authors":"Doris Titus-Glover","doi":"10.1017/cts.2024.194","DOIUrl":"https://doi.org/10.1017/cts.2024.194","url":null,"abstract":"OBJECTIVES/GOALS: This study explored personal recovery support, including social determinants of health and psychosocial needs to understand factors for sustaining recovery among parenting and pregnant women with opioid use disorder. METHODS/STUDY POPULATION: This study used a mixed method quantitative/qualitative design and recruited women from residential/transitional facilities in an urban area. We used the Accountable Health Communities Health-Related Social Needs tool to assess social determinants of health factors, level of physical activity, family/community support, and mental health (stress). Through focus groups, we interviewed women to describe challenges to recovery and to resources including access to providers, housing, childcare, and food assistance from lived experiences. RESULTS/ANTICIPATED RESULTS: Survey analysis showed social determinants of health factors such as food and transportation were partially mitigated by residential living; however, parenting and pregnant women with opioid use disorder remained concerned about housing and finances; and encountered low levels of physical activity and significant stress. Preliminary results from the focus groups revealed a theme of positive recovery and retention experiences from residential living. DISCUSSION/SIGNIFICANCE: Evidence from studies suggests focused interventions for recovering women to reduce relapse risk factors and adverse maternal outcomes. Opportunities for improving personal recovery capital are accessible in residential facilities, however, further exploration of unmet social determinants of health factors are needed for recovery retention.","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"3 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"509 Regulatory Lens of a QA/QC Project Manager","authors":"Rachel Bennett, Christine Sego Caldwell","doi":"10.1017/cts.2024.433","DOIUrl":"https://doi.org/10.1017/cts.2024.433","url":null,"abstract":"OBJECTIVES/GOALS: The primary purpose of the QA/QC Project Manager (PM), appointed under the NCATS UL1 administrative supplement award, is to facilitate quality and timely NCATS prior approval submissions preventing study start delays. Other goals include supporting these projects’ IRB applications and monitoring to ensure data quality and compliance. METHODS/STUDY POPULATION: At the Indiana CTSI, the QA/QC PM is assigned to the Regulatory Knowledge and Support program (RKS) and functions as a unique regulatory service provider. Through monitoring, auditing, and personalized consultations, the IN CTSI QA/QC PM provides study teams with regulatory, GCP, and other compliant study conduct insights while managing NCATS prior approval and RPPR submission quality and timeliness. In contrast to many CTSAs, this role is uniquely situated within RKS and provides QA/QC support through a regulatory lens. The Indiana CTSI QA/QC PM serves on the CTSA QA/QC Lead Team collaborating with NCATS and other CTSA QA/QC personnel. The Lead Team engages with NCATS to host monthly/quarterly meetings and participate in a discussion forum of NCATS and other CTSA QA/QC personnel. RESULTS/ANTICIPATED RESULTS: Not all CTSAs employ the QA/QC PM as regulatory support and the role and skill sets at each CTSA vary, yet the collaborative nature of these individuals across the CTSAs facilitates sharing of resources and knowledge. While prior approval and RPPR submissions vary widely, the QA/QC PMs can rely on their counterparts for guidance complying with the same regulations and policies within unique research settings and institutional nuances. The IN CTSI QA/QC PM, in collaboration with the QA/QC Lead Team, provided quality assurance revisions to the NCATS prior approval instructions which were adopted and published by NCATS January 2022 for implementation at all CTSAs. Ongoing, quality control efforts are accomplished through education, monitoring, and regulatory consultations. DISCUSSION/SIGNIFICANCE: As the research environment evolves, the QA/QC PM responsibilities shift in response to needs within RKS and NCATS. The versatility of the position enables QA/QC to occur at all stages of a study. QA/QC strategies aim to facilitate communication, quality NCATS prior approval and RPPR submissions, and compliance with proposed study conduct.","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"19 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"376 Pathophysiology of voluntary motor commands in patients with multiple sclerosis identified using reverse engineering of motor unit population discharge.","authors":"Laura McPherson, Tanner Reece, Skyler Simon, Keith Lohse, Francesco Negro, Catherine Lang, Robert Naismith, Anne Cross","doi":"10.1017/cts.2024.331","DOIUrl":"https://doi.org/10.1017/cts.2024.331","url":null,"abstract":"<p>OBJECTIVES/GOALS: Our objective is to characterize excitatory, inhibitory, and neuromodulatory components of the voluntary motor command at the level of the spinal motoneuron in people with multiple sclerosis (MS). This information will provide insight into neural mechanisms of motor dysfunction and their heterogeneity among patients with MS. METHODS/STUDY POPULATION: Due to advances in high-density surface EMG (HDsEMG) decomposition and the recent development of a paradigm for reverse engineering of motor unit population discharge, we can feasibly estimate aspects of excitatory, inhibitory, and neuromodulatory components of the voluntary motor command in humans on a person-specific basis. We tested 11 ambulatory patients with MS and mild-moderate disability. We recorded HDsEMG from tibialis anterior (TA) and soleus (SOL) during isometric plantarflexion and dorsiflexion, performed as slow triangle contractions. EMG was decomposed into motor unit spike trains using blind source separation. We calculated a number of motor unit variables, most notably delta-F, which estimates motoneuron excitability and the balance of neuromodulatory and inhibitory inputs. RESULTS/ANTICIPATED RESULTS: There were consistent differences in MS patients vs. controls. For TA, values were decreased for delta-F (3.9 vs. 5.9 pps), initial firing rate acceleration (5.8 vs. 7.1 pps), firing rate range (9.3 vs. 11.9 pps), and max firing rate (12.3 vs. 15.0 pps). SOL had more modest decreases in delta-F (3.0 vs. 3.8 pps) and firing rate range (4.8 vs. 5.6 pps). Self-sustained firing was longer for MS patients. Within a patient, abnormalities in motor unit variables were not consistent across muscles and legs. Interestingly, there were several abnormalities in the patients with a normal clinical motor exam, indicating that perhaps our measures are sensitive to subclinical changes in processing of voluntary motor commands. DISCUSSION/SIGNIFICANCE: Excitatory, inhibitory, and neuromodulatory components of the voluntary motor command must be appropriately balanced for skilled motor output. This study is the first to characterize how they are disrupted in MS, providing foundational information to inform the development of mechanistically-based rehabilitation interventions.</p>","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"34 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"417 Identifying Biomarkers of Social Threat Sensitivity Associated with Social Anxiety and Depressive Symptoms in Adolescents","authors":"Madison Politte-Corn, Kristin A. Buss","doi":"10.1017/cts.2024.361","DOIUrl":"https://doi.org/10.1017/cts.2024.361","url":null,"abstract":"OBJECTIVES/GOALS: Increases in anxiety and depression during adolescence may be related to increased biological reactivity to negative social feedback (i.e., social threat sensitivity). Our goal was to identify biomarkers of social threat sensitivity, which may provide unique etiological insight to inform early detection and intervention efforts. METHODS/STUDY POPULATION: Adolescents aged 12-14 (N=84; 55% female; 80% White; 69% annual family income &lt;$70,000) were recruited. Youth viewed a series of happy, neutral, and angry faces while eye-tracking and electroencephalogram (EEG) data were recorded to capture cognitive and neural markers of sensitivity to social threat (i.e., an angry face). Fixation time and time to disengage from angry faces were derived from eye-tracking and event-related potentials were derived from EEG, which index rapid attention capture (P1), attention selection and discrimination (N170), and cognitive control (N2). Adolescents also completed a social stress task and provided salivary cortisol samples to assess endocrine reactivity. Social anxiety and depressive symptoms were self-reported concurrently and one year later. RESULTS/ANTICIPATED RESULTS: Latency to disengage from threatening faces was associated with lower N2 amplitudes (indexing poor cognitive control; r= -.24, p = .03) and higher concurrent social anxiety (r = .28, p = .01). Higher N170 amplitudes, reflecting attentional selection and discrimination in favor of threatening faces, predicted increases in depressive symptoms one year later (b= .88, p = .02). No other neurophysiological measures were associated with each other or with concurrent or prospective symptomatology. DISCUSSION/SIGNIFICANCE: Eye-tracking and EEG measures indexing difficulty disengaging from social threat and poor cognitive control may be biomarkers of social anxiety, which could be utilized as novel intervention targets. High N170 amplitudes to social threat, derived from EEG, may have clinical utility as a susceptibility/risk biomarker for depressive symptoms.","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"60 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"444 Deciphering the role of IL-4 in post-colitis repair","authors":"Nicolas F Moreno, Yang Yang, Jong-Min Jeong, Vivian Tran, Yankai Wen, Constance Atkins, Jie Zhao, Yuanyuan Fan, Junda Gao, Cynthia Ju","doi":"10.1017/cts.2024.381","DOIUrl":"https://doi.org/10.1017/cts.2024.381","url":null,"abstract":"OBJECTIVES/GOALS: Incomplete mucosal healingand dysbiosis prevent long-term remission after colitis. IL4 may restore colon homeostasis through its action on immune cells and the microbiome. We will demonstrate this mechanism using genetically modified mice and molecular tools. This may result in target therapies that prolong remission in patients with IBD. METHODS/STUDY POPULATION: Mice were treated with 3% dextran sulfate sodium (DSS) in drinking water for 5 days to induce colitis. Mice were monitored daily for changes in body weight, and to monitor colitis severity. At each endpoint, mice were sacrificed and colon length was measured. For disease severity assessment, mouse colons were prepared in paraffin sections by the 'swiss-rolling' method. For flow cytometry, lamina propria mononuclear cell isolation was performed and cellular populations were stained with fluorophore-conjugated antibodies. IL4-eGFP-expressing (4get) mice were used to analyze the cellular expression of IL4 after colitis. Cell-specific IL4 deletion mice were generated using the cre-lox system. RESULTS/ANTICIPATED RESULTS: IL4-deficient mice had worse colitis compared with wild-type controls. Flow cytometry of lamina propria cells from 4get mice showed that most IL4-producing cells after colitis are eosinophils (CD11b+SiglecF+). Flow cytometry of C57bl6 mice showed an influx of IL4Ra+ monocytes (CD11b+Ly6C+) and macrophages (CD11b+F480+). IL4-stimulated bone marrow-derived macrophages demonstrated an increase in HB-EGF mRNA transcription. Myeloid-specific IL4R deleted mice had no difference in colitis severity compared with controls. Neutrophil-specific IL4R-deleted mice had increased colitis severity and mortality. Co-housing of littermate mice rescued recovery after DSS in IL4 deficient mice. DISCUSSION/SIGNIFICANCE: IL4 appears to play a role in restoring homeostasis after colitis. The mechanism depends on eosinophil-derived IL4, and action through neutrophils. However, the reparative function of IL4 can be shared with deficient mice through the microbiome. I will study the cellular and microbial mechanism by which IL4 restores homeostasis after colitis.","PeriodicalId":15529,"journal":{"name":"Journal of Clinical and Translational Science","volume":"34 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}