ABSTRACT IMPACT: This work will inform and improve the way we assess and treat distress in women with endometrial cancer. OBJECTIVES/GOALS: Distress from cancer is associated with worse processes of care. Differences in outcomes by race/ethnicity in endometrial cancer (EC) are well documented, but differences in distress have not been previously explored. Here we characterize the association between race/ethnicity, distress scores, and stressors reported by patients with EC. METHODS/STUDY POPULATION: Patients presenting to a single academic outpatient gynecologic oncology practice for initial evaluation of known EC from January 2013-May 2020 were included. The electronic health record was used to abstract demographics, National Comprehensive Cancer Network Distress Thermometer and Problem List (NCCN DT) scores and stressor categories (physical, emotional, spiritual, practical, and family) from the initial encounter. Referral to support services occurs at NCCN DT score ≥4. We excluded women who received prior cancer-directed therapy and those without an initial NCCN DT score. Summary statistics were tabulated for demographics. Mann-Whitney U tests were used for inter-group difference on continuous variables and 2-sample tests for equality of proportions were used for binary variables. RESULTS/ANTICIPATED RESULTS: 412 non-Hispanic White (NHW, mean age 63) and 149 non-Hispanic Black (NHB, mean age 65) women were included in our analysis. More NHB women presented with high-grade EC (53.7%) vs NHW women (21.9%) and fewer NHB women were privately insured (32% vs 52%). Median distress scores were higher in NHW women compared to their NHB counterparts (4 vs. 2, p<0.001) and NHB women were more likely to report a distress score of 0 compared to their NHW counterparts (32% vs 19%, p=0.001). 50.5% NHW women had a score ≥4 and thus qualified for referral to services compared to 20.7% of NHB women (p=0.02). Of those referred, NHB and NHW women declined referral to support services at similar rates (35.1% vs 34.5%; NS). There was a significant difference in the median number of stressors reported by NHW and NHB women, (4 vs 3 stressors; p=0.02). DISCUSSION/SIGNIFICANCE OF FINDINGS: The NCCN DT, a widely used tool in cancer clinics, may fail to adequately measure distress in NHB women presenting with a diagnosis of EC, despite >30% more high-risk histology cancers in this cohort. This difference leads to disparities in referral to additional support services, which may affect quality of care and quality of life.

OBJECTIVES/GOALS: The peer-reviewed journal Progress in Community Health Partnerships (PCHP) promotes health research partnerships to improve community health. PCHP’s Writing, Dissemination and Reviewer Learning Community Pilot aims to increase stakeholders writing and reviewing for greater relevance and diversity. METHODS/STUDY POPULATION: Led by PCHP’s Editorial Team, Morehouse SOM, Community-Campus Partnerships for Health (CCPH) and a community-academic Workgroup, the LC will guide stakeholders on scholarly writing and publish collaborative research. It builds on the 2017 Writing/Dissemination Learning Institute held by Morehouse, CCPH, and Community Based Organization Partners with the APHA Public Health Caucus. The LC begins with a Workshop [https://sites.google.com/view/pchp2023/pchpcommunity2023] alongside the 2023 APHA Annual Meeting. Wrap arounds include a PCHP Special Issue (participants work), Webinars, PCHP Reflections/Community Perspectives Article Guidelines [https://www.press.jhu.edu/journals/progress-community-health-partnerships-research-education-and-action], “Beyond the Manuscript [https://open.spotify.com/show/2LiBanXAyHyOqNSeGnBPHs]” Podcast, Toolkit/Resources; and coaching. The evaluation will inform PCHP practices. RESULTS/ANTICIPATED RESULTS: Key outcomes include successful implementation of all LI activities. The cohort (approximately 40 stakeholders representing partnerships) will increase exposure to scholarly writing and peer review, ideally publish 12+ manuscripts (e.g., PCHP special issue), increase diversity in scholarly writing, and strengthen recognition/significance of stakeholder authorship in the research community. The year 1 pilot evaluation (e.g., tracking participant authorship, documenting outcomes/lessons learned) will provide evidence to encourage sustainability, model responsiveness among other peer reviewed journals, inform PCHP, and increase diversity in scholarly writing on health disparities research. DISCUSSION/SIGNIFICANCE: The pilot will build a sustainable model and how PCHPaddresses health disparities to increase diversity, equity, and inclusion. The LC aims to diversify framing community health research, supporting/publishing stakeholders work, and increasing diversity among reviewers, all impacting the field.

OBJECTIVES/GOALS:

• Conduct an environmental scan of Marion County (Indianapolis) neighborhoods using electronic medical record data, state health data, and social and economic data

• Develop strong network of community collaborators

• Conduct a thorough assessment for each targeted neighborhood by listening and understanding the pressing health issues in the community and working together to design and deliver solutions

METHODS/STUDY POPULATION:

• Identify measures in the 3 domains of vulnerability, health and assets for the targeted neighborhoods and conduct bivariate descriptive statistics and multivariable regression analyses to investigate association between measures of vulnerability and health outcomes.

• Initiate relationships with leaders and residents in targeted neighborhoods

• Locate organizations working in targeted neighborhoods through online mapping software and word-of-mouth at neighborhood events, and created a spreadsheet with contact information.

• Conduct multidisciplinary assessment (i.e. key informant interviews, focus groups, town hall meetings) of the targeted neighborhood.

• Iteratively synthesize assessments to develop areas of interest and relevance to the community.

• Develop a road map for solutions identified by the community.

RESULTS/ANTICIPATED RESULTS: The results from the environmental scan conducted will be displayed in a report and visual “map” of health outcomes and health determinants, including assets and barriers for the targeted neighborhoods. The research team will use results from the environmental scan coupled with listening activities including attendance at community events, key informant interviews and focus groups to develop relationships and strong collaborations with the targeted neighborhood stakeholders. The relationship building between the research team and community will provide increased trust and engagement that will further enhance the effectiveness of the assessments completed with the targeted neighborhood. The assessments will help to empower communities to develop sustainable solutions and drive future work that will lead to future grant applications and larger-scale implementation in other community impact hub neighborhoods. DISCUSSION/SIGNIFICANCE OF IMPACT: Through the community impact hub work, we will develop collaborative efforts with targeted neighborhoods with the greatest health inequities in the Marion County area. In partnership with these neighborhoods, we will build a foundation – a network of community collaborators and a focused plan – upon which we will improve the health outcomes of residents while learning best practices on how to do so.

OBJECTIVES/SPECIFIC AIMS: While hospital-hospital transfers of pediatric patients is often necessary, some pediatric transfers are potentially avoidable. Pediatric potentially avoidable transfers (PAT) represent a process with high costs and safety risks but few, if any, benefits. To better understand this issue, we described pediatric inter-facility transfers with early discharges. METHODS/STUDY POPULATION: We conducted a descriptive study using electronic medical record data at a single-center over a 12-month period to examine characteristics of pediatric patients with a transfer admission source and early discharge. Among patients with early discharges, we performed descriptive statistics for PAT defined as patient transfers with a discharge home within 24 hours without receiving any specialized tests, interventions, consultations, or diagnoses. RESULTS/ANTICIPATED RESULTS: Of the 2414 pediatric transfers 31.2% were discharged home within 24 hours. Among transferred patients with early discharges, 348 patients (14.4% of total patient transfers) received no specialized tests, interventions, consultations, or diagnoses. Direct admissions were categorized as PAT 2.2-fold more frequently than transfers arriving to the emergency department. Among transferred direct admissions, PAT proportions to the neonatal intensive care unit (ICU), pediatric ICU, and non-ICU were 5.8%, 17.4%, and 27.3%, respectively. Respiratory infections, asthma, and fractures were the most common PAT diagnoses. DISCUSSION/SIGNIFICANCE OF IMPACT: Early discharges and PAT are relatively common among transferred pediatric patients. Further studies are needed to identify the etiologies and clinical impacts of PAT, with a focus on direct admissions given the high frequency of PAT among direct admissions to both the pediatric ICU and non-ICU.

OBJECTIVES/SPECIFIC AIMS: Background: The importance of engaging community in research and fostering community-academic research partnerships is increasingly acknowledged by Clinical and Translational Science Award (CTSA) institutes. However, forming and maintaining such collaborations is often hampered by numerous challenges. It is critical to investigate the barriers to effective community-academic partnerships and to develop novel approaches to overcome these barriers. Objective: To explore community and academic perspectives of the challenges faced by community-academic research partnerships and potential solutions to these identified challenges. METHODS/STUDY POPULATION: Methods: In an effort to explore creative approaches to address these issues, the Community Engagement Program at the Michigan Institute for Clinical & Health Research (MICHR), the CTSA site that serves Michigan, hosted a retreat to elicit the input of community members and academics from across the state. There was a mix of participants ranging from those with established community-academic partnerships to others who were new to community-engaged research and in early stages of forming partnerships. At the retreat, attendees were randomly divided into groups and asked to answer the specific question, “What are your barriers to partnering in research?” After each group identified a set of barriers and reported their findings to the entire room, attendees were asked to work again in their small groups to discuss potential solutions to these barriers. Ideas for solutions were also shared with the entire room. As part of the process of brainstorming about these questions, attendees were asked to document their ideas --- for both barriers and solutions --- on post-it notes which were then grouped by category. Artifacts from the retreat were saved digitally and transcripts made from these records. The findings were then analyzed to identify common themes. RESULTS/ANTICIPATED RESULTS: Results: Eighty-six participants attended the retreat from across the state of Michigan. Forty-three represented community organizations that focus on addressing a wide array of social determinants of health issues. The remaining forty-three participants represented various academic institutions. The most frequently mentioned challenges to community-academic partnerships were related to communication and relationship building. To overcome barriers in these areas, participants noted that it is critical to collaboratively and explicitly identify shared goals, values and norms in the early stages of partnership development. This was closely linked to the need for additional funding to help foster and strengthen relationships by allowing partners to spend time together to both work and socialize informally, preferably in face-to-face settings. These were deemed crucial for building trust and common ground. In addition, more equitable funding and role distribution --- including shared leadership and governance of research projects between community and academia--- that recognizes and supports the true costs of involvement in research for community members was viewed as important. Other frequently noted issues on the part of community members were the need for greater respect for community partners and for more training opportunities to build capacity within communities to participate in research. Participants from academic institutions emphasized that the current requirements and timeline for promotion in academia make it harder for them to participate in community-engaged research, especially as early career researchers. They maintained that wider recognition of the value of community-engaged research is necessary and that this requires the support of home departments. Finally, participants underscored the importance of building infrastructure to better connect potential partners from the community and academia by making it easier to identify common interests and reciprocal strengths. DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusion: The problems faced by community-academic partnerships may be alleviated by working with community and academic members to identify potential solutions. Further work is needed to systematically examine barriers and the efficacy of solutions to enhance community-academic partnerships. Acknowledgements: We thank all attendees of the MICHR Community Engagement retreat for their participation in this activity that explored barriers to effective community-academic partnerships. Their honest and frank feedback was essential to broaching sensitive topics related to partnership development, and to identify realistic and practical solutions. We also thank all members of the planning committee and our colleagues in the Community Engagement Program for their work on bringing together community and academic members for this retreat. This project was supported by grant number UL1TR002240 from the National Center for Advancing Translational Sciences (NCATS).

Justice-involved youth (JIY) have high rates of behavioral health disorders, but few can access, much less complete, treatment in the community. Behavioral health treatment completion among JIY is poorly understood, even within treatment studies. Measurement, reporting, and rates of treatment completion vary across studies. This systematic review and meta-analysis synthesizes the literature on rates of treatment completion among JIY enrolled in research studies and identifies potential moderators. After systematically searching 6 electronic databases, data from 13 studies of 20 individual treatment groups were abstracted and coded. A meta-analysis examined individual prevalence estimates of treatment completion in research studies as well as moderator analyses. Prevalence effect sizes revealed high rates of treatment completion (pr = 82.6). However, analysis suggests a high likelihood that publication bias affected the results. Treatment groups that utilized family- or group-based treatment (pr = 87.8) were associated with higher rates of treatment completion compared to treatment groups utilizing individual treatment (pr = 61.1). Findings suggest that it is possible to achieve high rates of treatment completion for JIY, particularly within the context of family- and group-based interventions. However, these findings are limited by concerns about reporting of treatment completion and publication bias.

Understanding place-based contributors to health requires geographically and culturally diverse study populations, but sharing location data is a significant challenge to multisite studies. Here, we describe a standardized and reproducible method to perform geospatial analyses for multisite studies. Using census tract-level information, we created software for geocoding and geospatial data linkage that was distributed to a consortium of birth cohorts located throughout the USA. Individual sites performed geospatial linkages and returned tract-level information for 8810 children to a central site for analyses. Our generalizable approach demonstrates the feasibility of geospatial analyses across study sites to promote collaborative translational research.

OBJECTIVES/SPECIFIC AIMS: Determine timing of risk of readmissions within 30 days among patients first discharged to a skilled nursing facilities (SNF) after heart failure hospitalization and subsequently discharged home. METHODS/STUDY POPULATION: This was a retrospective cohort study of patients with SNF stays of 30 days or less following discharge from a heart failure hospitalization. Patients were followed for 30 days following discharge from SNF. We categorized patients based on SNF length of stay (LOS): 1–6 days, 7–13 days, 14–30 days. We then fit a piecewise exponential Bayesian model with the outcome as time to readmission after discharge from SNF for each group. Our event of interest was unplanned readmission; death and planned readmissions were considered as competing risks. Our model examined 2 different time intervals following discharge from SNF: 0–3 days post SNF discharge and 4–30 days post SNF discharge. We reported the hazard rate (credible interval) of readmission for each time interval. We examined all Medicare fee-for-service (FFS) patients 65 and older admitted from July 2012 to June 2015 with a principal discharge diagnosis of HF, based on methods adopted by the Centers for Medicare and Medicaid Services (CMS) for hospital quality measurement. RESULTS/ANTICIPATED RESULTS: Our study included 67,585 HF hospitalizations discharged to SNF and subsequently discharged home [median age, 84 years (IQR; 78–89); female, 61.0%]; 13,257 (19.2%) were discharged with home care, 54,328 (80.4%) without. Median length of SNF admission was 17 days (IQR; 11–22). In total, 16,333 (24.2%) SNF discharges to home were readmitted within 30 days of SNF discharge; median time to readmission was 9 days (IQR; 3–18). The hazard rate of readmission for each group was significantly increased on days 0–3 after discharge from SNF compared with days 4–30 after discharge from SNF. In addition, the hazard rate of readmission during the first 0–3 days after discharge from SNF decreased as the LOS in SNF increased. DISCUSSION/SIGNIFICANCE OF IMPACT: The hazard rate of readmission after SNF discharge following heart failure hospitalization is highest during the first 6 days home. Length of stay at SNF also has an effect on risk of readmission immediately after discharge from SNF; patients with a longer length of stay in SNF were less likely to be readmitted in the first 3 days after discharge from SNF.

OBJECTIVES/SPECIFIC AIMS: The objective of this study is to determine predictors and motives for sustained opioid use, prescription misuse, and nonmedical opioid use in the adolescent trauma population. METHODS/STUDY POPULATION: This is a prospective cohort study that will follow patients for 1 year and administer surveys to patients on prescription opioid usage; substance use; utilization of pain management and mental health services; mental and physical health conditions; and behavioral and social risk factors. Patient eligibility criteria include: (1) patient is 12–18 years of age; (2) admitted for trauma; (3) english speaking; (4) resides within Indianapolis, IN metropolitan area; and (5) consent can be obtained from a parent or guardian. Patients with severe brain injuries or other injuries that prevent survey participation will be excluded. The patient sample will comprise of 50 traumatically injured adolescents admitted for trauma who will be followed for 12 months after discharge. RESULTS/ANTICIPATED RESULTS: We expect that the results of this study will identify multiple risk factors for sustained opioid use that can be used to create targeted interventions to reduce opioid misuse in the adolescent trauma population. Clinical predictors such as opioid type, dosage, and duration that can be modified to reduce the risk of long-term opioid use will be identified. We expect to elucidate clinical, behavioral, and social risk factors that increase the likelihood adolescents will misuse their medication and initiate nonmedical opioid use. DISCUSSION/SIGNIFICANCE OF IMPACT: Trauma is a surgical specialty that often has limited collaboration with behavioral health providers. Collaborative care models for trauma patients to adequately address the psychological impact of a traumatic injury have become more common in recent years. These models have primarily been concerned with the prevention of post-traumatic stress disorder. We would like to apply the findings of our research to better understand what motivates adolescents to misuse pain medications as well as how clinical, individual, behavioral, and social factors affect medication usage. This may help identify patients at greater risk of developing a SUD by asking questions not commonly addressed in the hospital setting. For example, similar to how trauma centers have mandated brief interventions on alcohol use be performed for center verification, screening patients’ on their social environment may identify patients at greater risk for SUD than assumed. The long-term goal would be to prevent opioid use disorders in injured adolescents by providing better post-acute care support, possibly by developing and implementing a collaborative care model that addresses opioid use. Additionally, we believe our findings could be applied in the acute care setting as well to help inform opioid prescribing and pain management methods in the acute phase of an injury. Genetic testing to determine which opioid to prescribe pediatric surgical patients is starting to be done at some pediatric hospitals. Certain genes determine which specific opioid is most effective in controlling a patient’s pain and, further, using the optimal opioid medication can also reduce overdose. Our findings may help refine prescribing patterns that could increase or decrease the likelihood of developing SUD in patients with certain genetic, clinical, behavioral, and social characteristics.

OBJECTIVES/GOALS: This study explored whether gabapentin (GBN) differentially impacted heart rate variability (HRV) and whether HRV was associated with opioid withdrawal ratings among participants with opioid use disorder (OUD) undergoing a randomized, double blind placebo-controlled, trial (RCT) of GBN during a buprenorphine (BUP)-assisted taper. METHODS/STUDY POPULATION: Participants (ages 18-64) with OUD, no recent use of benzodiazepines/barbiturates, and no major psychiatric disorders or unstable medical conditions were enrolled in the RCT, inducted onto BUP starting week 1 day 1 and randomly assigned to receive adjunct GBN or placebo starting week 1 day 3. All participants began a 10-day BUP-taper beginning week 2 day 3. HRV measures were assessed on week 1 day 2 (before GBN/placebo induction), week 2 day 2, and week 3 day 5 (end of BUP taper). HRV metrics were analyzed using Two Sample T-Test to determine differences between GBN vs. Placebo. Correlations between HRV metrics and opioid withdrawal ratings administered at the above timepoints will be analyzed using Spearman correlation. RESULTS/ANTICIPATED RESULTS: 28 participants underwent at least 1 HRV session that resulted in usable data. Preliminary statistical analyses revealed that HRV trended lower for GBN subjects during PB exercises than Placebo subjects, demonstrated by a higher mean heart rate for GBN subjects compared to Placebo subjects (p=0.0506) at the end of the BUP-taper (week 3 day 5). We expect future analyses to demonstrate a negative correlation between certain HRV metrics indicative of parasympathetic tone and opioid withdrawal rating assessment scores indicative of withdrawal severity. Such findings would demonstrate an association between opioid withdrawal severity and lower parasympathetic tone and HRV. DISCUSSION/SIGNIFICANCE: Individuals with OUD have previously been shown to have a lower parasympathetic tone than individuals without OUD. Additionally, opioid withdrawal has been shown to be associated with reduced parasympathetic tone. Our initial findings suggest that adjunct GBN administration was not associated with lower parasympathetic tone during PB exercises.

OBJECTIVES/GOALS: A quarter of Puerto Rican pediatric population are overweight or obese. Pediatric obesity is established as a global public health concern that will develop liver complication as a Non-alcoholic fatty liver disease (NAFLD). This study aims to determine the association between body weight, liver size and texture in Puerto Rican pediatric population. METHODS/STUDY POPULATION: Twenty-nine (n=29) pediatric participants (20 unhealthy weight and 9 healthy weight) between 7 to 19 years underwent panoramic ultrasound imaging of the RLL. Craniocaudal RLL measurement and liver texture were evaluated. Body mass index and waist circumference were also compared. Shapiro-Wilk test and students t-tests were attained with significance at p < 0.05. RESULTS/ANTICIPATED RESULTS: Statistical differences were detected between healthy weight and unhealthy weight pediatric patients: (1) RLL craniocaudal diameter (p=0.006); (2) waist circumference (p < 0.001); (3) BMI (p < 0.001). Unhealthy weight (overweight and obese) pediatric patients presented a greater number of livers with fat infiltration (13) and hepatomegaly (15). DISCUSSION/SIGNIFICANCE: This preliminary results showed that liver size was larger and fatty infiltration are relatively frequent among overweight and obese pediatric patients. Prevention of unhealthy weight and the diagnosis of changes in liver texture and size among pediatric patients is important to prevent progressing of liver disease and avoid irreversible damage.

ABSTRACT IMPACT: Understanding gene expression changes after viral vaccination and booster may help predict vaccine efficacy. OBJECTIVES/GOALS: Utilize a systems biology approach to identify gene expression changes after administration of Zaire Ebola virus glycoprotein expressed in a Chimp Adeno3 vector (ChAd3-EBOZ) and either boosted ˜7 weeks later with modified vaccinia Ankara MVA expressing Zaire and Marburg GPs plus Tai forest NP (MVA-BN ®Filo) or given saline (placebo). METHODS/STUDY POPULATION: As part of the phase 1b, open-label vaccination trial of ChAd3-EBO-Z in Mali, West Africa, peripheral blood mononuclear cells were isolated from eight volunteers for whole genome transcriptomics analysis. Four subjects received the MVA-BN ®-Filo booster and four received saline. Samples were taken prior to receipt of the booster or placebo, as well as 1, 7, and 14 days afterwards. Significant differentially expressed genes were identified using RNA-seq between baseline and post-MVA-BN ®Filo. Functional enrichment analysis against the GO Ontology Database and the Immune Signatures C7 collection of MSigDB (ImmuneSigDB) was performed. These differentially expressed genes were also examined for associations with Ebola antibody titers and cell-mediated immune responses. RESULTS/ANTICIPATED RESULTS: The majority of gene expression changes occurred on day 1 post-MVA-BN ®-Filo administration. 870 genes had significantly different expression when day 1 samples were compared to pre-booster baseline (791 upregulated/79 downregulated). Those upregulated genes are mainly involved type I interferon and regulation of viral life cycle pathways. The downregulated genes are involved in regulation of cellular defense response, lymphocyte mediated immunity. Comparing to the C7 Immune Signatures collection datasets, we identified more than 100 upregulated genes from 6 studies of yellow fever vaccination that were also significantly upregulated in our study. The top enriched ontological pathway of those genes is cellular response to type I Interferon. DISCUSSION/SIGNIFICANCE OF FINDINGS: The use of a systems biology approach to compare gene expression changes among vaccine studies utilizing whole genome transcriptomics data allows the identification of genes involved in the immune response to vaccination and might aid in predicting vaccine efficacy.

OBJECTIVES/GOALS: Theater has always served as a means of reflecting and understanding the human condition. Participatory theater further offers the option for viewers to participate in and thus additionally benefit from the performance itself. We use Playback Theater for outreach and research, eliciting information to guide research, education, and engagement. METHODS/STUDY POPULATION: Playback Theater is a type of improvisation that involves audience members recounting personal experiences which are then enacted by a theater troupe. Playback has evolved to include storytelling as a means of expressing and understanding difficult life experiences such as violence, bullying, incarceration, disaster, illness, etc. While not intended as therapy, it has been found to provoke insight and catharsis when used by trained practitioners. We are conducting Playback theater with LGBTQ+ and African American women to elucidate health disparities related to HIV/AIDS. Black/African Americans accounted for 42.1% of cases in 2019, and African American females are 15 times more likely to develop AIDS than white females. We hope to elucidate barriers to screening and treatment to inform early intervention. RESULTS/ANTICIPATED RESULTS: In community engagement, we employ a variety of strategies involving storytelling, since this simple act fosters multiple positive outcomes. For example, by talking about their experiences participants might find clarity about a difficult experience, facilitating coping or healing, or even letting go. By sharing their stories, others (clinicians, researchers, other patients, or the public) can learn what it is like to go through a particular illness or event. This knowledge can be used to allay patient fears or help researchers or clinicians to develop programming that better responds to needs. This novel approach to knowledge sharing also allows communication that may not otherwise be possible. Discussions about sensitive topics are enabled, often leading to shared understanding and potential solutions. DISCUSSION/SIGNIFICANCE: Through Playback Theater, we hope to identify and thus be able to address barriers to early screening and treatment for African American women and the LGBTQ+ population. We are also planning an event with children with cancer and their families to better understand their experiences and needs in both the clinical and familial settings.

OBJECTIVES/GOALS: We have shown that glioblastoma upregulates blood-brain barrier drug efflux transporters via a mechanism that likely involves TNFα and PI3K/Akt. Our goal is to repurpose FDA-approved PI3K/Akt inhibitors to increase anticancer drug brain concentrations, which holds the potential for translation into the neuro-oncology clinic. METHODS/STUDY POPULATION: GL261 Red-FLuc and MBR525-1 Red-FLuc cells (2μl; 2.5K cells/μl; 1μl/min) were injected into the right hemisphere of 8-week old female J:NU mice (coordinates relative to bregma: AP -2 mm, ML -2 mm, DV -3 mm). Tumor burden was assessed weekly with IVIS® Spectrum in vivo imaging; tumor volume and invasiveness were measured by MRI and histopathology, respectively. On day 14 post-injection, mice received 5-ALA (200 mg/kg ip), and tumors were resected with a 2 mm punch biopsy tool and surgical fluorescence microscope (ex/em: 405/635nm). Drug efflux transporter expression and activity in isolated brain capillaries were determined by Western blot and substrate fluorescence assays, respectively. Cytotoxicity was assessed after 48-hour drug incubation using CyQuant MTT Cell Proliferation Assay kits. RESULTS/ANTICIPATED RESULTS: IC50 values of temozolomide, lapatinib, alpelisib, and miltefosine were N/A, 32, 20, and 190 μM for GL261 Red-FLuc cells and N/A, 49, 36, and 148 μM for MBR525-1 Red-FLuc cells, respectively. Median survival of GL261 Red-FLuc mice was 26.5d and significantly increased to 34d with resection (p=0.116). In GBM mice, drug efflux transporter expression and activity levels in brain capillaries isolated from the contralateral hemisphere were significantly upregulated compared to sham controls. Furthermore, treatment with FDA-approved PI3K/Akt inhibitors, alpelisib and miltefosine, significantly reduced drug efflux transporter expression and activity to control levels. In PK and survival studies, we expect that PI3K/Akt inhibition will increase brain uptake of anticancer drugs and prolong GBM mouse survival. DISCUSSION/SIGNIFICANCE: We have previously shown that PI3K/Akt inhibition reduces P-gp/BCRP levels in brain capillaries. Here, we vertically extend this strategy by repurposing the FDA-approved PI3K/Akt inhibitors alpelisib/miltefosine to improve brain uptake of anticancer drugs in GBM resection models.

OBJECTIVES/SPECIFIC AIMS:.Outline the development and purpose of the partnership brokering database in REDCap. Provide an overview of the tool and how it works. Discuss how this tool facilitates partnership-brokering activities and discuss plans for future use METHODS/STUDY POPULATION: Research Electronic Data Capture (REDCap) is a secure, web-based application developed at Vanderbilt University to assist with systematic data management of small and medium sized projects. CCH utilized REDCap to build a custom data management warehouse entitled the Partnership Brokering Tool. Information compiled in various formats (handwritten notes, spreadsheets, etc.) over the past 10 years by CCH staff, was then systematically organized and entered into the Partnership Brokering Tool. The tool captures information such as individual contact information, organizational affiliation (academic, community, faith, government etc.), research interests (35 categories - asthma, diabetes, heart disease, etc.), communities of foci (children, elderly, LGBTQ, ethnicity, etc.), and target geographic community served (Chicago north, south, suburban, Illinois, etc.). RESULTS/ANTICIPATED RESULTS: Data was compiled on 451 community groups and organizations and 77 partners in academia thus far. Community organizations represent a range of community sectors including advocacy and policy groups, community-based, faith-based organizations, foundations, media, schools, etc. throughout the Chicagoland area. Data analysis activities are underway, however, results will also be shared regarding characteristics of the communities these organizations serve including:. Age range. Special populations (as defined by the CSTI grant). Underrepresented racial and ethnic communities. DISCUSSION/SIGNIFICANCE OF IMPACT: The Partnership Brokering Tool has provided a format for CCH to systematically gather information about the relationships staff have cultivated with community groups and organizations. Unlike an email management system, this REDCap project is highly useful in capturing the parameters of our partner pool, identifying partnership gaps, and matching individuals interested in collaborating with researchers or community organizations that have a particular skill set or research interest. The Partnership Brokering Tool has also facilitated stakeholder engagement dedicated to guiding the centers’ overall goals, objectives, and programming. Finally, utilizing REDCap has streamlined efforts in reporting quantitative and qualitative data about these organizations. In the next phase of this project, CCH will utilize the database to assess the nature of the relationship between CCH and community groups and organizations.

OBJECTIVES/GOALS: While anti-seizure medications are effective, nearly one third of patients have seizures that go untreated. Prior studies using evoked seizure models have shown that activation of the Superior Colliculus (SC) display anti-seizure effects. Here we monitored and modulated the DLSC to suppress spontaneous seizures in a genetic model of epilepsy. METHODS/STUDY POPULATION: WAG/Rij rats (4 months old) were employed as study subjects. Animals were surgically prepared for virus injection (ChR2 excitatory opsin, or control vector), fiber optic implantation and cortical EEG for optogenetic studies. For In vivo electrophysiology, animals were implanted with a 16 wire multi-electrode array into the DLSC. In optogenetic experiments, we compared the efficacy of continuous neuromodulation to that of on-demand neuromodulation (real time detection of seizures) paradigms on a within-subject basis. We compared three stimulation frequencies on a within-subject basis (5, 20, 100 Hz). We quantified the number and duration of each spike wave discharge (SWD) during each two-hour-long trial. Electrode array single units were sorted and analyzed for activity before, during and after seizures. RESULTS/ANTICIPATED RESULTS: In vivo electrophysiology found there to be a significant decrease in single unit activity leading up to the start of SWDs. Interestingly, on-demand neuromodulation was effective in both females and males – where the greatest reduction in seizure duration was under 100 Hz light delivery. As expected, male and female animals injected with a control vector did not show a reduction in seizures in response to light delivery. In the open-loop (continuous) stimulation paradigm, optogenetic activation of the DLSC was without effect on the number or duration of SWDs at any of the frequencies examined. DISCUSSION/SIGNIFICANCE: SC activity is significantly decreased prior to the start of seizures. Furthermore, activation of the SC displays anti-seizure effects in a model of spontaneous seizures. A striking difference between open and closed-loop neuromodulation approaches underscores the importance of stimulation paradigm in determining therapeutic effect.

OBJECTIVES/GOALS:

• The podcasts highlight work from our partners: Indiana University, Purdue University and the University of Notre Dame.

• Our goal is to expand our podcast reach to include work from at least three additional CTSAs, as well as highlighting the benefits of translational research to the public.

METHODS/STUDY POPULATION:

• Aaron E. Carroll, is the director of Education and Workforce Development for the Indiana CTSI and a popular writer covering health, research, and policy for The New York Times. He is host of the Indiana CTSI-sponsored Healthcare Triage podcasts as well as the Healthcare Triage YouTube show, with 340,000 subscribers. We will leverage his audience and research expertise to grow the Indiana CTSI podcast participation and increase audience engagement.

• We will eventually allow the nation-wide network of CTSAs to pitch guests and shows covering Translational Research, and invite local CTSA leadership or faculty to participate in the podcast.

RESULTS/ANTICIPATED RESULTS:

• Utilizing quantitative analytics, we expect to see a significant increase in podcast downloads and listeners as we expand our offering to other CTSAs, beyond Indiana

• We expect that the CTSA-wide podcast will increase the nationwide level of knowledge and understanding of NCATS, translational research, and its benefits to society and healthcare.

• We anticipate, through this expanded podcast offering, a growing number of community members who are informed and engaged on the topics of translational research, clinical and translational sciences and beyond.

DISCUSSION/SIGNIFICANCE OF IMPACT:

• Podcasts are a convenient, portable, and efficient form of science communication.

• Podcasts also make information personal and offer us an excellent and innovative communications vehicle to spread the word about translational research, as well as the excellent work happening at each of our CTSAs.