OBJECTIVES/GOALS: The purpose of this work is to assess antibiotic prescribing for inpatients with community-acquired bacterial pneumonia (CABP) due to methicillin-resistant Staphylococcus aureus (MRSA) in the All of Us database. The goal of this research is to determine if different subgroups are more or less likely to receive anti-MRSA antibiotics. METHODS/STUDY POPULATION: This is a retrospective cohort study of inpatients with CABP due to MRSA from 2/1/2011 to 7/1/2022 in the All of Us database. Cases will be excluded for other treatment settings, other pathogens, and other types of pneumonia. Patients will be stratified by age, sex, race, and ethnicity. The proportion of patients who received anti-MRSA antibiotic therapy will be compared within groups with the chi-square statistic. Significant associations between patient characteristics and anti-MRSA prescribing (p < 0.05) will be assessed using multivariate logistic regression, with subgroup as the independent variable, anti-MRSA prescribing as the dependent variable, and divergent baseline characteristics as potential confounders. Odds ratios (OR) and 95% confidence intervals (95% CI) will be calculated. RESULTS/ANTICIPATED RESULTS: Previous research by our group has demonstrated differences in guideline-concordant, empiric antibiotic prescribing, for inpatients with CABP in the All of Us database; however, guideline-concordant empiric antibiotics for CABP do not routinely cover for MRSA. Anti-MRSA antibiotics are recommended if the patient has known MRSA or risk factors for MRSA. Investigations of disparity in anti-MRSA prescribing have been limited, especially since the abandonment of the healthcare-associated pneumonia (HCAP) categorization. Since the All of Us database contains information on CABP pathogens, we can study sub-types of CABP; therefore, we now hypothesize that the proportion of inpatients who received anti-MRSA antibiotics for CABP, due to MRSA, in the All of Us database, will differ by age, race, sex, and ethnicity. DISCUSSION/SIGNIFICANCE: This is one of the first studies to evaluate antibiotic prescribing for CABP due to MRSA in the All of Usdatabase. Identifying and understanding differences in care, such as possible discrepancies in anti-MRSA prescribing by age, sex, race, or ethnicity, is essential to develop targeted interventions to address disparities in health outcomes.

OBJECTIVES/GOALS: To demonstrate the value of the Competency Index for Clinical Research Professional (CICRP) as a tool in program evaluation using a pre- and post- design to evaluate student perceived self-efficacy in clinical trial competencies at program entry and at program completion. METHODS/STUDY POPULATION: Using a separate-sample pre-post study design, we administered the CICRP questionnaire to students in the entry and exit courses of the Master of Clinical Research (MCR) Program during the 2021-2022 academic year, using QualtricsTM (Provo, Utah) survey instrument for use on desktop or mobile device. We included the 20 CICRP competency items asking students to rate their self-efficacy in performing each item using a Likert Scale (from 0-10) (0=not at all confident; 10= extremely confident). Links to the survey were included in the courses for the foundational entry course and for the final culminating project course. RESULTS/ANTICIPATED RESULTS: Overall, 54 students took the CICRP during the entry course and 56 during the exit. Cronbach’s alpha for each assessment ranged from 0.93 to 0.98. Both the Welch’s two-sample t-test and Wilcoxon rank-sum test show very significant differences between the group of students entering the program and leaving the program (p value < 0.001). A significant increase in mean CICRP total score is seen at each experience level between program entry and program exit (p<0.001) A linear regression, adjusting for available covariates, individuals taking the exit course have a mean CICRP total score 92.690 (p value < 0.001) higher than individuals taking the entry course. DISCUSSION/SIGNIFICANCE: Competency indices have been used to measure self-efficacy in translational research scientists, thus the use of CICRP to measure self-efficacy can be useful in assessing whether our competency-based program is meeting the JTF Competency needs of students.

OBJECTIVES/GOALS: Globally, diabetes affects 537 million people and 15-25% will develop a foot ulcer in their lifetime. Diabetic foot ulcers (DFU) tend to be chronic and non-healing due to the poor wound healing environment, leading to infection or amputation. Our study aims to develop a method to predict and prevent DFU formation. METHODS/STUDY POPULATION: Our preliminary plan is to develop a method to detect high plantar pressures, coupled with the ability to automatically adjust an orthotic device to offload excess pressure. Our current aim is to create a “smart orthotic” which will link with foot mapping technology to automatically offload high pressure areas, reducing the need for a separate clinic visit for orthotic adjustment. We aim to prove that our device will normalize plantar pressure distribution, which will prevent callus and subsequent DFU formation. The current target population includes those with diagnosed diabetes and are ambulatory. RESULTS/ANTICIPATED RESULTS: With our technology, we anticipate normalization of plantar pressure distribution in a more frequent fashion than is currently done. Because annual orthotic fittings, which is current standard of care, do not provide regular enough adjustments to match the rate of diabetic foot structural changes and peak plantar pressure redistribution, our device will address two gaps in management. One, patients will receive near-instantaneous changes in plantar pressure offloading, allowing for near continuous orthotic customization. Secondly, our device would reduce the clinical appointment burden, which would be especially important for patients with multiple medical comorbidities or experience other barriers to accessing healthcare. DISCUSSION/SIGNIFICANCE: While DFUs are commonplace and their complications are well recognized, there still exists a gap in ulcer prevention. Our proposed solution will redistribute pathologic plantar pressures, allow for more frequent monitoring, automatic therapy, and aid in the management of high ulcer risk patients.

OBJECTIVES/GOALS: We are using ethnographic methods and Dissemination and Implementation (D&I) frameworks to study barriers and facilitators to implementing ‘TeamMAPPS: Team Methods to Advance Processes and Performance in Science.’ TeamMAPPS is an evidence-based Team Science curriculum deployed as five online modules and being implemented across CTSA hubs. METHODS/STUDY POPULATION: For this pre-implementation study, we used the Implementation Mapping framework to understand likely barriers and facilitators, with the aim of designing implementation strategies and long-term outcome measures. Data included field notes from a two-day train-the-trainer, one visit to a key implementing site, and 27 interviews. Participants were four TeamMAPPS conceptualizers, four module designers, and 15 implementers from seven implementing sites, each with a CTSA hub (four were interviewed twice). We coded transcripts using the Consolidated Framework for Implementation Research (CFIR) to identify contextual barriers and facilitators to D&I, the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) D&I outcomes framework, and target competencies of TeamMAPPS. RESULTS/ANTICIPATED RESULTS: Priority D&I outcomes that emerged were adoption, reach, and effectiveness. Potential barriers/facilitators to “adoption” included institutional willingness to incentivize scientists to utilize TeamMAPPS, support for Team Science at CTSAs, and systems of rewards for scientists to undergo trainings. Anticipated barriers/facilitators for “reach” were closely tied to adoption, such as institutions’ ability to persuade or require scientists to take trainings. Other issues relevant to reach included the time it takes to time to complete TeamMAPPS and potentially fraught intra-team dynamics arising if modules are implemented as a whole-team intervention. Anticipated barriers/facilitators for “effectiveness” included having adequate tools to assess actual impact. DISCUSSION/SIGNIFICANCE: TeamMAPPS has the potential to accelerate advances in translational sciences across the CTSA consortium. As this D&I study proceeds we will continue Implementation Mapping and use the Expert Recommendations for Implementing Change (ERIC) to develop bundles of implementer-informed strategies to the effectively deliver TeamMAPPS among CTSAs.

OBJECTIVES/GOALS: While strategies for community engagement in health research and clinical trials are well documented, participation from underserved populations remains low. Our research team conducted a series of Community Engagement Studios for community members to discuss what is still needed for them to engage in health research. METHODS/STUDY POPULATION: In the spring of 2023, our research team conducted four community engagement studios using the Vanderbilt Community Engagement (CE) Studio model. Community members were recruited through health councils- which are a community-led collaborative, focused on health at the county level throughout the state. In the CE Studio model community members or stakeholders are referred to as experts. In total, 31 experts from 12 different health councils from around the state participated in the CE Studios via Zoom. The CE Studios centered around two main questions 1.) What do communities want to know before agreeing to participate in research? And 2.) When a study is presented as an opportunity for your community, what things need to be addressed to see if it is a good fit? RESULTS/ANTICIPATED RESULTS: Themed summaries for each CE Studio and one overall themed summary were developed by a designated notetaker on the research team. Of novelty were cultural considerations for each region that included recommendations such as “Foster kinship between those doing the research and the community” speaking to the shared community bond that unites people and the need for researchers to also spend time creating meaningful community bonds throughout the research process. The CE Studio overall summary revealed two main themes for researchers: 1.) Things that help with research participation, and 2.) Things that get in the way of research participation. Overall themes echoed documented best practices for community engagement efforts. DISCUSSION/SIGNIFICANCE: Each CE studio revealed cultural considerations that included recommendations to researchers. Overall themes echoed documented best practices for community engagement efforts implying that while strategies for researchers to engage with communities are well known, more needs to be done to continue to implement these practices.

OBJECTIVES/GOALS: Low birth weight and preterm birth are significant contributors to infant mortality in the United States that disproportionally impact Black pregnant persons and their offspring. Although these outcomes are linked to chronic stress, the contribution of race-related stress remains largely understudied. METHODS/STUDY POPULATION: We investigated the effect of race-related stress on weight and gestational age at birth in a prospective cohort of 115 pregnant Black persons recruited at Grady Memorial Hospital in Atlanta, Georgia. The Index of Race-Related Stress Brief (IRRS-Brief), Perceived Stress Scale (PSS), and Stressful Events Questionnaire (SEQ) were collected at study enrollment during pregnancy. Neonatal birth weights and gestational age were collected via standardized medical record abstraction. We conducted linear regressions to determine whether greater race-related stress was associated with lower weight and gestational age at birth, while controlling for sources of prenatal stress. RESULTS/ANTICIPATED RESULTS: Global racism (total IRRS score) was significantly associated with birth weight when controlling for prenatal perceived stress and stressful life events within the last six months since study enrollment (beta=−16.7, p=.035). Neonatal gestational age was associated with both global racism (beta=-0.03, p=.028) and individual racism (IRRS’Individual’ subscale score) (beta=-0.09, p=.032) when controlling for prenatal perceived stress and stressful life events within the last six months since study enrollment. These results suggest that greater race-related stress contributes to lower weight and gestational age at birth in pregnant Black persons. DISCUSSION/SIGNIFICANCE: Future studies are necessary to determine the mechanisms by which race-related stress contributes to these adverse birth outcomes and to inform the development risk-assessment tools and interventions to mitigate the threat of race-related stress on adverse birth outcomes in high-risk populations.

OBJECTIVES/GOALS: Physicians can request the clinical use of investigational products for their patients through an FDA pathway called Expanded Access (EA). Most evaluations of EA focus on the FDA submission only. We sought to evaluate these requests through the full academic medical center process. METHODS/STUDY POPULATION: Through the Transforming Expanded Access to Maximize Support and Study grant, we reviewed regulatory records for single-patient EA requests at four institutions (Duke University, University of Rochester, University of Michigan, and University of Texas Southwestern) which occurred between June 1, 2021 and February 28, 2023. Key data was collected, including the investigational product requested, submission and approval dates, urgency of request, and indication for treatment. Descriptive statistics were performed with Microsoft Excel. RESULTS/ANTICIPATED RESULTS: A total of 405 EA requests were identified, of which 319 (78.8%) were for drugs, 59 (14.6%) for biologics, and 27 (6.7%) for medical devices. The majority were characterized as non-emergency (60.7%), but the proportion of emergency to non-emergency cases varied considerably when stratified by year, with a peak in emergency cases in 2020. The most common products included therapies for COVID-19 and Mpox. Median time to obtain all approvals for treatment was 7 days for emergency cases and 28 days for non-emergency. The FDA review took the least time, with a median of 1 day in non-emergency cases. Full board approval from an institutional review board in non-emergency cases was 7 days. DISCUSSION/SIGNIFICANCE: These results generally align with previous reports on EA submissions received by the FDA. The timelines for the EA process represent an important benchmark both for treatment planning and institutional improvement.

OBJECTIVES/GOALS: Distinguishing tumor tissue from normal brain parenchyma remains a major challenge during the resection of gliomas, leading to the persistence of tumor cells. This study aims to assess the choline kinase alpha-targeting fluorophore JAS239 as a novel fluorescent agent to intraoperatively visualize gliomas in an orthotopic murine model. METHODS/STUDY POPULATION: The human glioblastoma-derived U87 MG-Luc2 cell line will be intracranially implanted in nude mice and tumor growth will be assessed using bioluminescence imaging. After 14 days, the mice will be treated with either antiangiogenic therapy (10 mg/kg bevacizumab, twice/week) or saline (control). Tumor growth will be monitored until 21-28 days after initial implantation, at which point JAS239 (4.0 mg/kg, 90 min before sacrifice) and Evans Blue (4 ml/kg, 60 min before sacrifice) will be administered. The mice will be sacrificed, and their brains will be harvested and sectioned for near-infrared imaging. The brain sections will be processed for histopathologic analysis, allowing for the correlation of observed fluorescence with the distribution of tumor and comparison of signal-to-background ratios. RESULTS/ANTICIPATED RESULTS: JAS239 is an indocyanine-based choline mimetic (excitation 745 nm, emission 775 nm) that has been shown to cross the blood-tumor barrier (BTB) in rodent glioblastoma studies. PET imaging with choline-based radiotracers like 18F-choline has also been shown to delineate both contrast-enhancing tumor (CET) and non-contrast-enhancing tumor (NCET) regions, supporting the hypothesis that JAS239 will be able to visualize heterogeneous glioma tissue in our mouse model. Evans Blue is a passive dye in the visible light spectrum (excitation 620 nm, emission 680 nm) expected to only fluoresce in CET regions due to the disruption of the BTB. JAS239 is expected to fluoresce in both CET and NCET regions, which will be assessed by the fluorescence in mice treated with bevacizumab (expected to renormalize the BTB and model NCETs). DISCUSSION/SIGNIFICANCE: JAS239 may allow for real-time visualization of heterogeneous glioma tissue, which is important because there are no current intraoperative imaging agents for NCETs. Future research and clinical translation of this class of agents may allow surgeons to maximize the safe resection of gliomas, improving progression-free and overall survival rates.

OBJECTIVES/GOALS: Renal vascular resistance (RVR) is the opposition to blood flow by renal arteries. At the population level, dietary salt increases RVR and blood pressure (BP), which are associated with cardiovascular disease. Recent data indicate exogenous ketones may offset adverse cardiorenal effects of salt. METHODS/STUDY POPULATION: Our registered clinical trial (NCT05545501) is a double-blinded, placebo-controlled, crossover study. Participants are being randomized to three 10-day conditions: A) control; B) high salt; C) high salt and ketone supplementation. Ten participants are enrolled (target 30 participants). Renal blood velocity (RBV) in the renal and segmental arteries will be measured in the decubitus position using Doppler ultrasound during a 3-minute baseline and 3-minute cold pressor test. We will measure brachial BP with an automated oscillometric BP monitor. RVR will be calculated as mean BP divided by RBV. Statistical analyses will include ANOVA and correlations with α set at ≤ 0.05. RESULTS/ANTICIPATED RESULTS: We anticipate attenuated RBV and increased BP during the cold pressor test, particularly following high salt loading, leading to greater RVR. We hypothesize ketone supplementation will attenuate the high salt induced increase in RVR during the cold pressor test. In addition to RVR we will examine renal vascular conductance which is the ease with which blood flows through arteries, calculated as RBV divided by mean BP. Additional hemodynamics such as heart rate and systolic and diastolic BP will be reported and correlated with primary outcomes. DISCUSSION/SIGNIFICANCE: Dietary salt plays a role in hypertension, cardiovascular disease, and chronic kidney disease, which are leading causes of death. Ketone supplementation may be a promising approach to counteract the detrimental effects of high dietary salt and improve cardiovascular health in adults.

OBJECTIVES/GOALS: A barrier to the proliferation of team science is that academicians are often trained in disciplinary silos where “independent” research contributions are lauded. To tackle some of the most pressing scientific challenges, dismantling silos and increasing team science training efforts that focus on early career investigators is a must. METHODS/STUDY POPULATION: A team science training workshop for early career investigators from varied disciplinary backgrounds was informed by a 20-item needs assessment that addressed essential team science competencies and was completed by early career investigators participating in federally funded professional development programs on our campus. During the workshop, the benefits of cross-disciplinary teaming was discussed. Strategies including team formation, team effectiveness and/or dysfunction, diagnosing team strengths and weaknesses, and teaming in community settings were discussed. Instructional methods included short presentations, video clips, case studies, group discussions, pair and share activities, and panel discussions with expert role models encouraged active learning. RESULTS/ANTICIPATED RESULTS: The impact and value of the workshop series to participant’s professional development and knowledge of team science concepts will be evaluated before and after the workshop. Multiple Likert-scale items focused on team science competencies (e.g., confidence in your ability to carry out responsibilities specific to your role on a team, recognize when the team is not functioning well; engage team science practices in on-going research), and open-ended questions (e.g., importance of engaging community partners in academic research teams, vision of what factors contribute to an effective team science collaboration) will be completed by program participants before and after completing the workshop. DISCUSSION/SIGNIFICANCE: Effective collaboration among scientists with expertise in different disciplines is needed to address and solve complex scientific problems. We believe our interactive approach to team competency training sessions would work in a variety of settings and improve team skills.

OBJECTIVES/GOALS: Examine the use of Patient-Reported Outcomes (PRO) in Huntington’s Disease (HD) clinical trials (CT) and compare across time and sponsor types. METHODS/STUDY POPULATION: Conduct literature review on 1. background of HD, 2. what symptoms and outcome measures are most important to patients, including the Patient-Focused Drug Development (PFDD) meeting for HD–led by the U.S. Food and Drug Administration (FDA), 3. what outcome measure tools currently exist and what they measure. Utilizing Clinicaltrials.gov, trials for HD were examined to assess the number of trials conducted, what COAs were used, and funding types. Trials were filtered by study type (keep Interventional) and status (filter out suspended, terminated, unknown, and withdrawn). The frequency of COAs will then be mapped based on the symptoms from the PFDD meeting. RESULTS/ANTICIPATED RESULTS: From the PFDD meeting for HD, symptoms that were important to patients include cognitive impairment, depression and anxiety, and motor symptoms. From the 139 interventional studies that were active, complete, recruiting, or not recruiting, 79 studies were conducted by Industry, 3 by NIH, 93 by Other (Academia/Community Organizations), and 1 by a U.S. Federal Agency (other than NIH). One of the most commonly used COA is the Unified Huntington’s Disease Rating Scale (UHDRS), which includes a motor, cognitive, and behavior assessment, and an assessment on functional capacity and independence. Of the 27 out of 139 trials analyzed to date, there were a total of 37 COAs. DISCUSSION/SIGNIFICANCE: The widespread use of UHDRS can be attributed to its standardization in 1999. It captures the symptoms of HD that are most important to patients. Because UHDRS is not sensitive to any one symptom, other COAs have been developed which focus on unique aspects of HD and allow for its earlier detection.

OBJECTIVES/GOALS: Despite food pantries’ efforts to improve nutritional quality and encourage healthy cooking, limited evidence exists regarding pantry shoppers’ culinary preferences and kitchen equipment access. This project utilized pantry food demonstrations and samples to collect recipe and kitchen tool feedback. METHODS/STUDY POPULATION: For 4 months, a Culinary Medicine team delivered food demonstrations at Crossroads Community Services food market in Dallas, Texas, which serves primarily Hispanic and Black residents. Each demo provided a food sample, corresponding printed recipe in English or Spanish, and a survey. Part 1 of the survey measured shoppers’ hedonic liking of the sampled food and their likelihood of recreating it. Part 2 used the same scale for non-sampled recipes adapted from Health meets Food Community Culinary Medicine programming. Averages of appeal and likelihood to cook between sampled and unsampled groups were compared with a student’s T test. Part 3 contained a visual graphic of 24 kitchen appliances, and shoppers circled each item they owned. Investigators collected surveys from 207 shoppers across 12 demos. RESULTS/ANTICIPATED RESULTS: Preliminary analyses showed a positive response to the food demonstrations with a mean rating on a 5-point Likert scale of 4.58 for recipe appeal and 4.46 for likelihood of cooking the recipe at home. The Health meets Food recipes not demonstrated were also positively reviewed (4.40 for appeal and 4.32 for likelihood to cook). There was a statistically significant difference in appeal between sampled and non-sampled recipes (p = 0.03) while no significant difference was found for likelihood to cook (p = 0.08). On average, clients owned 75% of kitchen appliances with most clients owning a sauté pan (94%) but few having access to a food processor (27%). DISCUSSION/SIGNIFICANCE: An effective nutrition program for food pantry clients must be accessible, culturally relevant, nourishing, and enjoyable. Providing samples alongside recipes may increase appeal and engagement. Consideration of kitchen equipment access is essential to promote recipe recreation at home.

OBJECTIVES/GOALS: Antibiograms are used to guide empiric antibiotic selection. However, it is unclear if antibiotic profiles differ between symptomatic urinary tract infections (UTIs) and asymptomatic bacteriuria (ASB). We aimed to compare antibiotic susceptibility profiles of urinary E. coli isolates from patients with a symptomatic UTI to those with ASB. METHODS/STUDY POPULATION: We conducted a cohort study of 1,140 urinary E. coli isolates from unique patients that received care through Vanderbilt University Medical Center (VUMC) from Nov 2020 – Jun 2021. We included any patient that was seen at VUMC as an inpatient, outpatient or at the emergency department with ≥ 105 colony forming units/mL E. coli detected from a clinical urine specimen. Chart abstractions were performed to capture reported UTI symptoms and demographic information. Descriptive statistics were conducted to compare antibiotic susceptibility profiles (i.e., susceptible, intermediate, resistant) between symptomatic and ASB groups. The risk of detection of a multidrug-resistant organism (MDRO) (intermediate, or resistant to at least one antibiotic in three or more classes) was assessed between groups. RESULTS/ANTICIPATED RESULTS: Among 1,140, 1,018 (89%) and 122 (11%) were symptomatic and ASB, respectively. When comparing symptomatic and ASB, the median ages were 50 and 46. Groups had similar proportions of no indwelling catheter (94% v. 95%) and without diabetes (87% v. 88%). The collection setting between inpatient, emergency department, and outpatient were similar with most being outpatient (79% v. 83%). The proportion of patients who were pregnant, immuno compromised, or had a structural/functional urinary tract abnormality were higher in the symptomatic group. The proportion of isolates resistant and susceptible to tested antibiotics were similar between groups, with only ciprofloxacin showing slightly higher resistance among ASB (16% v. 25%). The risk of MDRO detection was similar between groups (RR: 0.858, 95% CI: 0.64, 1.15). DISCUSSION/SIGNIFICANCE: Antibiotic susceptibility comparison demonstrated similar profiles, which suggests antibiogram use as appropriate to guide ASB treatment. Results offer insight on whether traditional methods for assessing antibiotic susceptibility on population-levels could benefit from further refinement by patient-specific clinical parameters.

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.

OBJECTIVES/GOALS: Hypermobile Ehlers-Danlos syndrome (hEDS) is a heritable connective tissue disorder with no known genetic etiology. Its complex phenotypic presentation with multi-system involvement delays proper diagnosis and treatment, especially for females. This study examines the risk for common hEDS comorbidities and medical service utilization. METHODS/STUDY POPULATION: Electronic health records from over 150 million patients across 92 American healthcare servers were queried using the TriNetX database to determine phenotypic presentation of hEDS and risk of receiving comorbid diagnoses. Contingency tables were created with hEDS as the condition and postural orthostatic tachycardia syndrome (POTS) or gastroparesis as the grouping variables. Advanced analytics were conducted to compare outcomes of two cohorts: (1) patients diagnosed with hEDS and both POTS and gastroparesis, and (2) patients with a sole diagnosis of hEDS. After propensity score matching, differences in medical service utilization and mental health diagnoses were assessed between these two cohorts. All analyses restricted age (12-70 years) and employed established exclusion criteria (e.g., diabetes). RESULTS/ANTICIPATED RESULTS: TriNetX national health records (N = 1,968) reveal that hEDS predominantly affects females (87%) and is diagnosed at a mean of 35 years of age. People diagnosed with hEDS have a high prevalence of comorbid nervous system (81%), mental health (76%), and digestive system (69%) disorders. They are 29.7 times more likely to be diagnosed with POTS [95% CI: 27.1, 32.6] and 66.3 times more likely to be diagnosed with gastroparesis [95% CI: 56.5, 77.9], compared to people without hEDS. After propensity score matching for sex, race, and ethnicity, people diagnosed with hEDS and both POTS and gastroparesis have significantly greater service utilization (72.2% vs. 56.7%; z = 2.18, p < .05) but not a greater incidence of mental health disorders (34.4% vs. 24.4%; z = 1.47, p = .14) than people diagnosed with hEDS alone. DISCUSSION/SIGNIFICANCE: This study reveals the phenotypic presentation of hEDS and the elevated risk of co-occurring POTS and/or gastroparesis diagnosis. hEDS and its comorbidities are associated with more frequent medical encounters but not with a greater incidence of mental illness. Findings have implications for both clinical practice guidelines and further research.

OBJECTIVES/GOALS: It is estimated that 357,000 children have experienced a school shooting since 1999, yet due to limitations in the firearm violence field broadly, the sequalae are not well understood. The objective of this work is to examine the mental health impacts of school shootings, providing insight into the lasting effects of firearm violence on our communities. METHODS/STUDY POPULATION: We will first conduct a quasi-experimental study using controlled interrupted time series with repeated cross-sectional data to assess school shootings’ impact on US mental health. School shooting data is from the K-12 School Shooting Database, and mental health data will be collected via the Behavioral Risk Factor Surveillance System. Second, we will conduct focus groups with community organizations, school administrators, and the public. Interview guides will be developed to explore the mental health impacts of school shootings, to guide the quantitative results interpretation, and assess educational materials’ usefulness. Qualitative analysis will occur in NVivo software with codebook refinement through thematic analysis. Results will be triangulated through convergence coding. RESULTS/ANTICIPATED RESULTS: This research is situated within the context of the pervasive mental health challenges in the US, where mental illness poses significant health, social, and economic burdens. Thus, we anticipate finding an association between school shootings and decreased self-reported mental well-being among US adults. Literature suggests that there may be a stronger association among specific subgroups, such as parents with school-aged children or individuals living in close proximity to such incidents. We expect to find heterogeneity in the effect estimate based on school shooting attributes, such as the number of casualties. Through focus groups, we anticipate furthering our comprehension of the broad-ranging effects of school shootings on less quantifiable outcomes and the unique trajectories of recovery. DISCUSSION/SIGNIFICANCE: This project will contribute needed information on the impact of school shootings and mental health and assist in reducing the frequency and impact of school shootings. Furthermore, we aim to extend our findings beyond the scientific community, translating them into educational resources advocating for policy and public health interventions.

OBJECTIVES/GOALS: To determine in vitro mechanisms by which fruits and vegetables (FV) contribute to colon barrier development in Latin American infants. We hypothesize that simulated colonic fermentation of FVs will stimulatein vitro cell barrier function by activating the hypoxia-inducible factor (HIF) pathway in colonocytes. METHODS/STUDY POPULATION: FVs consumed by US-based Latin American infants 6-12 months old (identified from NHANES-What We Eat in America Surveys) will be combined with human breast-milk samples from women self-identified as Hispanic or non-Hispanic, and then subjected to in vitro digestion and anaerobic colonic fermentation using human feces. FV fermenta will be incubated with Caco2 monolayers to measure in vitro cell permeability and protein levels of cellular tight junction, metabolic, and HIF signaling enzymes. To examine their effects in vivo, FVs identified to modulate in vitro barrier function, will be fed (5% freeze dried powder) to wild-type mice and the above parameters will be examined. If in vivo effects are found, intestinal specific HIF knockout mice will be used to examine the role of HIF signaling in mediating these effects. RESULTS/ANTICIPATED RESULTS: We expect that fermenta derived from human milk and FVs will reduce in vitro gut permeability in Caco2 monolayers by increasing gene and protein expression of the HIF signaling complex relative to fermenta of human milk alone. This will be reflected with higher cellular trans-epithelial resistance and greater expression levels of tight junction proteins. We expect FV powder consumption will similarly increase in vivo gut permeability and expression of related genes in mice as compared to mice fed diets without FVs. As we expect an increase in HIF signaling in the colon, we expect that FV powder consumption will not enhance in vivo gut permeability in mice colons with an intestinal specific knockout of HIF. DISCUSSION/SIGNIFICANCE: Data from this study will provide mechanistic evidence to help clinicians promote relevant FVs recommendations for Latin American infants and families. Due to the link between gut permeability and obesity, our next step will be to conduct a dietary intervention in this population.

OBJECTIVES/GOALS: With the knowledge that population health will not improve without including community voices in research, analysis of the UCI Institute for Clinical and Translational Science (ICTS) Community-Campus Research Incubator (CCRI) grants awarded since 2010 provides the foundation for understanding research partnerships impact on community health. METHODS/STUDY POPULATION: Over the past 13 years, the UCI ICTS CCRI program has funded 63 partnered research pilot or capacity-building projects, providing up to $30K annually to academic-community partnerships. Each year since 2010, between 3 and 7 projects were funded up to $5,000 annually for capacity-building activities and up to $10,000 annually for pilot research activities. Additionally, during the COVID-19 pandemic, a collaboration between the UCI ICTS and the local Healthcare Agency provided up to $20,000 to research partnership teams to study impact and interventions related to the pandemic, where 10 CCRI awards were given out. Evaluations of these research teams was completed at the end of the project, and at years 2 and 3 after the project ended. Analysis of the projects and partnerships aim to reveal the impact of these projects. RESULTS/ANTICIPATED RESULTS: In 2023, we compiled all evaluation data collected from 2010 – 2023 from the CCRI partnership grants, including traditional metrics of publications, subsequent grant applications submitted & awarded, presentations given, and return on investment for ICTS granted funds. Less traditional metrics include number of students trained, new tools or databases created, knowledge disseminated, and advances in clinical care. Since 2020, Translational Science Benefit Model metrics have been collected on community, policy, economic, and clinical domains. Since 2015, data on each CCRI partnership has been collected at the start and end of each project, with questions about attributes of each partner, trust, community engagement principles, and anticipated/actual impact of each project. DISCUSSION/SIGNIFICANCE: Organizing outcomes from the data collected will provide deep understanding of important components, functioning, and types and reach of partnered health research. This understanding will inform future action of the CCRI program in terms of what can be accomplished with a given amount of funding, and the constitution of successful partnerships.

OBJECTIVES/GOALS: To establish the root causes of vaccine hesitancy in populations who have less equitable access to health and healthcare services, and experience healthcare inequities, related to the environmental and social determinants of health, through community engagement and conversations, collaboration, circulation, and communication. METHODS/STUDY POPULATION: Existing data from a cross-sectional survey, vaccine hesitancy (VH) parent study, entitled 'Western New York (WNY) COVID-19 Collaborative to Promote Vaccine Acceptance,' conducted July to November 2022, after IRB approval, will be qualitatively analyzed. In the parent study, surveys were administered in WNY community congregations and community centers to individuals that historically have less equitable access to healthcare resources and may encounter health and healthcare disparities. Minorities, in urban and rural areas, age eighteen and older were identified through the NYS Department of Health’s Immunization Information System for daily vaccination rates. A qualitative analysis, promoting fact base HL, and building an inferential statical machine learning tool are the next steps. RESULTS/ANTICIPATED RESULTS: We anticipate the results to show an interplay of multiple factors, including personal, cultural, historical, social, and political, and varies depending on circumstances of time, place, and the type of vaccine being offered. Additionally, a lack of awareness or understanding of vulnerabilities and seriousness of vaccine-preventable diseases, lack of trust in health care providers, social norms, distrust of the healthcare system, biomedical research, and government policy, limited knowledge and understanding of vaccine safety and efficacy, and fear/uncomfortable with needles, as well as the less addressed environmental and social determinants of health associated with racial/ethnic minorities in communities with limited resources may also contribute to VH and less favorable health outcomes. DISCUSSION/SIGNIFICANCE: Identifying people who historically have less equitable access to healthcare resources and may be more likely to resist healthcare services, due to distrust in the system is important. Creating and evaluating an innovative tool to predict refusal of public health interventions is essential to avoid spreading preventable diseases.

OBJECTIVES/GOALS: Tobacco use remains a significant public health problem in rural America. Community health centers (CHCs) can help reduce the burden of tobacco use in rural areas, but we know little about their knowledge and implementation of best practices for tobacco control. This study assessed the knowledge and existence of tobacco control practices in rural CHCs. METHODS/STUDY POPULATION: Using a cross-sectional study design, we electronically surveyed health administrators and providers (n=64) in six rural CHCs in Louisiana between March 2021 and June 2023. The assessment measured 1) knowledge of the U.S. Public Health Service Clinical Practice Guideline for Treating Tobacco Use, 2) the priority given to smoking cessation programming, 3) the presence of best practices for tobacco control programming, such as having a tobacco control champion and team, 4) establishment of treatment and smoke-free campus policies, and 5) existence of referral procedure to external cessation services. We used descriptive statistics to characterize survey participants and responses. RESULTS/ANTICIPATED RESULTS: Most of the respondents were female (80%), White (61.8%), between 35 and 49 years of age (48.1%), and non-smokers (72.7%). Only half (51.6%) reported knowledge of the guideline for treating tobacco use among all respondents. Only a third (32.8%) said their health center gave smoking cessation high priority relative to other health priorities. Only a third (35.9%) reported having a tobacco champion; less than a fifth (18.8%) said they had a tobacco control team at their health center. Although all health centers had a smoke-free campus policy, about a quarter (23.4%) were unaware of the policy. Less than a quarter (23.4%) reported having a written policy for smoking cessation treatment at their health center, and less than half (46.7%) knew about cessation services to which they could refer patients. DISCUSSION/SIGNIFICANCE: Rural CHCs had limited knowledge of the guideline for tobacco use treatment. Smoking cessation lacked priority, and the prevalence of tobacco control best practices implementation was low. Rural CHCs must improve their implementation of guideline-recommend policies and clinical strategies to promote treatment and reduce the burden of tobacco use.