OBJECTIVES/GOALS: Childhood Sjögren’s disease (cSD) is a rare autoimmune disease. Despite the profound impact on children and their families, pediatric-specific clinical trials to inform therapeutic strategies in cSD are lacking. In 2022 we participated in the Trial Innovation Network (TIN) Design Lab with the purpose of designing a series of N-of-1 trials for cSD. METHODS/STUDY POPULATION: New medications have the potential to be safe/effective treatments for cSD but must be evaluated in randomized trials. To overcome limitations of traditional parallel-group designs given the rarity of cSD, we developed an N-of-1 trial approach. Our proposal was selected by the Tufts TIN Design Lab. The Design Lab multi-stakeholder process involved parents of and patients with cSD, pediatric and adult rheumatologists, and experts in clinical trial design and outcomes. We engaged all stakeholders in protocol development to maximize the impact of the proposed approach on clinical care, ensure a successful recruitment plan, and inform the choice of endpoints as there are no widely accepted cSD outcome measures to determine treatment efficacy. RESULTS/ANTICIPATED RESULTS: Using the Design Lab methodology, we clarified the N-of-1 study goals and engaged in an iterative process to develop a “briefing book” that ensured a sound premise for our study. We reviewed and accumulated published literature to support our focus on mucosal/glandular manifestations, identified potential interventions to be used in the N-of-1 trials, and enumerated possible outcomes, including outcomes important to patient/parents. This work culminated in a full-day Design Lab event that included multiple stakeholders who provided expertise from different perspectives on the full drug development pathway. Study design feedback focused on three specific areas. 1) Inclusion and exclusion criteria; 2) Identification of outcome measures; 3) Treatment and washout periods. DISCUSSION/SIGNIFICANCE: To address the critical need and move treatment of cSD forward, we are designing a prototype N-of-1 trial in children with rheumatic disease. We will continue to engage stakeholders by using a series of Delphi surveys and an in-person meeting to create composite outcome measures to test cSD therapies in personalized trials.

OBJECTIVES/GOALS: The aim of thispaper is to raise awareness of the limitations of the current pMRI training paradigm and to recommend a standardization of skills to expand diversity among field-based neuroimaging technicians. METHODS/STUDY POPULATION: Currently, there are seven international brain research initiatives. The goal is to establish and understand the cultural values a society holds and how the outcomes of research may be adopted into societal practice. We must also consider the benefits of early detection amongst minoritized communities in neuroscience research. Neuroimaging in remote settings can allow patients to advocate more accurately for timely medical care which can lead to better health outcomes. According to the Journal of Neurological Sciences, neuroscience accounts for 9% of total medical publications. RESULTS/ANTICIPATED RESULTS: Neuroimaging research continues to evolve in terms of resolution and portability. T By harnessing diverse data, we are able to utilize advanced neuroimaging techniques and software technology to recognize trends amongst subgroups of individuals who were previously considered geographically inaccessible. DISCUSSION/SIGNIFICANCE: Despite the excitement and promise of portable neuroimaging devices, there is a fundamental need to establish standardized training procedures that can be accessed by individuals of all socioeconomic backgrounds.

OBJECTIVES/GOALS: Prostate cancer treatment is associated with significant genitourinary side effects. There is a critical need for treatment with decreased morbidity. We report the development of a novel treatment paradigm combining irreversible electroporation and lower dose radiation to provide prostate cancer patients with a less morbid treatment. METHODS/STUDY POPULATION: Intermediate risk prostate cancer patients will undergo focal irreversible electroporation followed by low dose, whole gland radiation therapy. The primary endpoint is freedom from clinically significant cancer on biopsy at 12-month follow up. Secondary endpoints include safety profile, oncologic efficacy, effectiveness of RT and need for secondary treatment. This trial (NCT05345444) and currently actively recruiting patients after initial feasibility trial. Sample size is calculated to detect an increase in the proportion of patients who are cancer free at 1-year, from 0.80 to 0.95. An exact binomial test with a 10% one-sided significance level will have 94.3% power to detect the difference between the null and alternative hypothesis when the sample size is 42. RESULTS/ANTICIPATED RESULTS: This is a clinical trial in progress. DISCUSSION/SIGNIFICANCE: Combined irreversible electroporation (IRE) and a lower dose radiotherapy (RTIRE) may provide prostate cancer patients a treatment with minimal side effects.

OBJECTIVES/GOALS: Congenital cytomegalovirus (cCMV) remains to be the leading infectious cause of fetal anomalies. The role of fetal natural killer (NK) cells during cCMV remains largely unknown. The objective of this study is to define the transcriptomes of fetal NK cells exposed to human cytomegalovirus (HCMV) infection during gestation. METHODS/STUDY POPULATION: Four sets of umbilical cord blood and matching umbilical cord tissues were collected from two HCMV seropositive (HCMV+) and two HCMV seronegative (HCMV-) fetuses that did not experience any complications during gestation. These samples were provided by the Medical College of Wisconsin Tissue Bank and were processed within 24 hours following live birth. CD7+ CD3e-CD14-CD19-CD20- fetal NK cells were isolated, using the BD FACSAria sorter. Following cell sorting, single-cell RNA sequencing (scRNA-seq) was performed, and cDNA libraries were constructed and sequenced via NextSeq 550. Cell Ranger was then used to algin the cDNA reads and the Seurat R package was used to analyze the transcriptional data. Cells were filtered and clustered based on the number of uniquely expressed genes. RESULTS/ANTICIPATED RESULTS: Four sets of umbilical cord blood and matching umbilical cord tissues were collected from two HCMV+ and two HCMV- fetuses. We were able to successfully sort and capture fetal NK cells and perform scRNA-seq on these samples. Following unbiased clustering, we observed and characterized five distinct fetal NK cell subsets in the umbilical cord blood and four fetal NK cell subsets in the corresponding umbilical cord tissue. Our findings revealed that HCMV+ fetal NK cells primarily consisted of mature NK cell subsets, while HCMV- fetal NK cells constituted the majority of the immature subsets. Importantly, we identified a unique subset of NKG2CHi fetal NK cells that were significantly elevated in the HCMV+ fetuses. Finally, we defined a group of transcription factors involved in the formation of antiviral fetal NK. DISCUSSION/SIGNIFICANCE: Here, we demonstrate that HCMV infection can induce the formation of distinct NK cell subsets and drive their unique transcriptional profiles. These findings have the potential to guide the development of an innovative NK cell immunotherapy that could help prevent fetuses from developing symptomatic cCMV.

OBJECTIVES/GOALS: The primary research goal was to identify brain alterations reliably associated with obesity using coordinate-based meta-analysis. A secondary goal was to compare brain alterations in metabolically healthy (MHO) and unhealthy (MUO) obesity. METHODS/STUDY POPULATION: Source data were peer-reviewed studies reporting locations of gray-matter alterations in group-average, case-control contrasts (obese vs. non-obese) cohorts, performed in a whole-brain, voxel-wise manner. Both voxel-based morphometry and voxel-based physiology studies were included. Three coordinate-based meta-analyses were performed: Pooled (MUO + MHO), MHO, and MUO. RESULTS/ANTICIPATED RESULTS: Thirty-two studies reporting a total of 50 case-control contrasts (MHO, 23; MUO, 27) met inclusion criteria, representing 3,368 participants (obese, 1,781; non-obese, 1587). The pooled analysis yielded 8 cerebral foci (3 nuclear, 5 cortical) in regions implicated in reward-seeking, cognitive, and interoceptive behaviors. MHO yielded 7 cerebral foci (4 nuclear, 3 cortical), partially overlapping Pooled results, with similar behavioral loadings. The MUO pattern was distinct, with 3 cerebellar and 1 occipital foci. DISCUSSION/SIGNIFICANCE: Brain alterations occurred reliably in obesity. The dominant pattern (Pooled & MHO) involved cerebral reward-system circuits, evident even in metabolically healthy obesity. Cerebellar alterations occurred exclusively in metabolically unhealthy obesity, a pattern previously reported in metabolic syndrome.

OBJECTIVES/GOALS: The objective of this study is to assess the feasibility and preliminary impact of a physiotherapy protocol for developing an individualized home-based physical activity program to increase physical activity (PA) levels in sedentary older adults with Type II Diabetes Mellitus (T2DM) living in Puerto Rico (PR). METHODS/STUDY POPULATION: This will be a pilot study with two phases. In phase 1, we will design a novel patient-centered home-based PA program protocol for adults ≥65 years with T2DM based on the Information-Motivation-Behavioral Skills model. Its content validity will be assessed through focus groups with 10 experts and 10 older adults and analyzed using a directed content analysis. Phase 2 we will be program implementation using a one-group, repeated measures design with 12 adults ≥65 years with T2DM. PA levels will be assessed by recording active minutes with a Fitbit. Risk of falls, balance, strength, and physical function will be assessed through standardized tests validated for this population. Statistical analysis will include descriptive statistics, comparisons via chi-square/Fisher’s exact test, and non-parametric tests. RESULTS/ANTICIPATED RESULTS: We expect to recruit a minimum of 12 participants and to administer the program for 12 weeks at a frequency of two visits per week. We anticipate that implementing and supervising the home-based PA protocol will be feasible as determined by recruitment and retention rates, patients’ satisfaction, and compliance with the program. We also expect that this protocol will increase physical activity levels, improve general strength, balance, physical function, and reduce the risk of falls in sedentary older adults with T2DM. DISCUSSION/SIGNIFICANCE: As the third cause of death in PR, T2DM represents a public health challenge. An effective home-based PA program may decrease morbidity and mortality rates in older adults by increasing PA and functional health. This study will provide data for planning a randomized controlled trial to assess its effectiveness in the outcomes of interest.

OBJECTIVES/GOALS: The objectives of the Academy of Community Reviewers (ACR) serve to: (1) provide comprehensive education and training to community members about clinical research and the community review process for clinical research grants; and (2) collaborate with the community in the development of the training to ensure benefice and meaningful engagement. METHODS/STUDY POPULATION: This training targets community members who will serve as future grant reviewers for The Ohio State University Center for Clinical Translational Science (CCTS) pilot grant submissions, other grant submissions and as expert consultants on other projects needing community perspectives. In 2019 and 2020, this training was offered as a live session. Thirty-eight community reviewers were trained and have served as grant reviewers and consultants on over 70 projects. Based on feedback of former graduates, time demands, logistics, and technology advances warranted transitioning the course to an online learning platform. ACR graduates were consulted in course redesign and updates. Course revisions include material on DEIA, implicit bias and health equity in clinical research with narrated lectures. RESULTS/ANTICIPATED RESULTS: Each of the 7 modules (including a total of 15 submodules) will have a brief summary knowledge check. The module “How to incorporate diversity, equity, inclusion and accessibility in health research” will invite trainees to independently explore their own social identity and biases through a guided exercise. The last (7th) module will have interactive opportunities for submitting grant reviews and participation in an online grant review session, geared to The Ohio State University CCTS. ACR graduates have been invited to consult on educational material and pilot the new course. Demographic, knowledge assessments and module evaluations will be collected. An overall course evaluation and focus group interviews with graduates will also be analyzed for quality improvement and contributions in grant reviews. DISCUSSION/SIGNIFICANCE: The increased accessibility of the ACR course will foster more inclusive community engagement and support the development of clinical and translational research that is innovative, efficient, equitable, and relevant to its beneficiaries. This in depth community reviewer training has been designed to be used and customized to other CTSA Hubs.

OBJECTIVES/GOALS: To evaluate the association of maternal delivery history with a brachial plexus birth injury (BPBI) risk in subsequent deliveries, and to estimate the effect of subsequent delivery method on BPBI risk. METHODS/STUDY POPULATION: We conducted a retrospective cohort study of all livebirth deliveries occurring in California-licensed hospitals from 1996-2012. The primary outcome was recurrent BPBI in a subsequent pregnancy. The exposure was prior delivery history (parity, shoulder dystocia in a previous delivery, or previously delivering an infant with BPBI). Multiple logistic regression was used to model adjusted associations of prior delivery history with BPBI in a subsequent pregnancy. The adjusted risk (AR) and adjusted risk difference (ARD) for BPBI between vaginal and cesarean delivery in subsequent pregnancies were determined, stratified by prior delivery history, and the number of cesarean deliveries needed to prevent one BPBI was determined. RESULTS/ANTICIPATED RESULTS: Of 6,286,324 infants delivered by 4,104,825 individuals, 7,762 (0.12%) were diagnosed with a BPBI. Higher parity was associated with a 5.7% decrease in BPBI risk with each subsequent delivery (aOR 0.94, 95%CI 0.92, 0.97). Previous shoulder dystocia or BPBI were associated with 5-fold (aOR=5.39, 95%CI 4.10, 7.08) and 17-fold increases (aOR=17.22, 95%CI 13.31, 22.27) in BPBI risk, respectively. Among individuals with a history of delivering an infant with a BPBI , cesarean delivery was associated with a 73.0% decrease in BPBI risk (aOR=0.27, 95%CI 0.13, 0.55), compared with an 87.9% decrease in BPBI risk (aOR=0.12, 95%CI 0.10, 0.15) in individuals without this history. Among individuals with a previous history of BPBI, 48.1 cesarean deliveries are needed to prevent one BPBI. DISCUSSION/SIGNIFICANCE: Parity, previous shoulder dystocia, and previously delivering a BPBI infant are associated with future BPBI risk. These factors are identifiable prenatally and can inform discussions with pregnant individuals regarding BPBI risk and planned mode of delivery.

OBJECTIVES/GOALS: Maternal opioid use disorder (OUD) is linked to poor fetal outcomes. While it has been established that opioids can cross from maternal to fetal circulation, the mechanisms underlying these adverse outcomes remain poorly defined. This study aims to uncover OUD-associated immunological changes in maternal and fetal circulation. METHODS/STUDY POPULATION: To study the effect of maternal OUD on the maternal immune system at delivery, we collected maternal blood samples at delivery from healthy pregnant women (controls) and pregnant women with a diagnosis of severe OUD. To study the impact of maternal OUD on newborn immunity, we also collected umbilical cord blood (UCB) at delivery. Flow cytometry was used to determine the frequency and phenotype of circulating immune cell subsets and responses to stimulation. Isolated monocytes were stimulated with bacterial/viral agonist cocktails, while T and NK cells were stimulated with PMA/ionomycin. The impact of maternal OUD on circulating immune mediators was determined by Luminex and on monocyte activation markers sCD14 and CRP by ELISA. RESULTS/ANTICIPATED RESULTS: In maternal circulation, OUD was associated with a significant decrease in markers of inflammation, cell proliferation, and activation. Frequencies of immune cell subsets were impacted by OUD, shown by an expansion of CD8+ EMRA T cells, marginal-zone B cells, mDCs, non-classical monocytes, and CD16low NK cells. While no differences were seen in T and NK cell responses to stimulation, monocytes and pDCs had significantly lower responses to bacterial and viral agonist stimulation. Analysis of UCB revealed increased levels of pro-apoptotic/T cell exhaustion mediators and pro-inflammatory cytokines, albeit decreased levels of several chemokines and growth factors. The UCB immune landscape is altered with maternal OUD, as demonstrated by a shift from naive to memory CD8+ T cells and a decrease in pDC frequency. DISCUSSION/SIGNIFICANCE: OUD dampens maternal peripheral immunity, possibly contributing to poor placental function or premature/delayed labor. Monocytes and pDCs lack antimicrobial functionality, suggesting increased infection susceptibility with OUD. Finally, these implications extend to the fetal compartment, shown by heightened immune activation in UCB.

OBJECTIVES/GOALS: We aim to characterize how Heligmosomoides polygyrus bakeri (H. poly) alleviates murine allergic asthma which shares many characteristics of human asthma. This approach of has already identified helminth-produced human immune cell ligand “mimics” that hold great potential for next-generation clinical biologics METHODS/STUDY POPULATION: We examined the lung tissue of C57BL/6 mice infected with H. poly for changes in the pulmonary microenvironment. At ten days post infection, four infected mice and two co-housed uninfected mice were sacrificed, and their lung tissue harvested for examination of RNA via RT-qPCR. This design allows for the comparison between the lung microenvironments of infected and naīve mice. In future experiments, we intend to characterize what small molecules produced by the helminth drive changes in the lung using germ-free models of H. poly infection. RESULTS/ANTICIPATED RESULTS: We found key differences in lung chemokines between mice infected with H. poly and naīve mice. Using a student t-test with naīve correction for variance, we were able to show significant differences in the expression of E cadherin (p = 0.0355), CXCL10 (p = 0.0025), CX3CL1 (p = 0.0029), CCR2 (p = 0.017), and IDO1 (0.0078). We also found that differences in the expression of CCL5 bordered on significant with a p-value of 0.066. The expression of most of these markers (CXCL10, CCR2, CCL5, and IDO1) was elevated in the lungs of infected mice compared to naīve controls. In contrast, E cadherin and CX3CL1 showed the opposite trend with naīve mice showing greater expression. These clear differences in lung tissue gene expression underscore the connection between the gastrointestinal and pulmonary mucosal immune compartments. DISCUSSION/SIGNIFICANCE: The changes are unexpected for an infection that has been shown to attenuate allergic inflammation in the lung with increases in the IFN-Y responsive genes IDO1 and CXCL10 and inflammatory lung markers, CCL5 and CCR2. In contrast, there were decreases in inflammatory lung marker CX3CL1 and the tight junction protein E cadherin in infected mice.

OBJECTIVES/GOALS: Non-operative management is preferred for pediatric solid organ injury (SOI). Despite this children treated at adult trauma centers (ATC) are more likely to be treated surgically and have worse outcomes than those treated at pediatric trauma centers (PTC). We hypothesize there are disparities by sex and race in management of pediatric SOI at ATC vs PTC. METHODS/STUDY POPULATION: Retrospective review of the National Trauma Data Bank (NTDB) from 2010-2018 was conducted. Inclusion criteria were age£18 and injury to spleen, liver or kidney. Outcomes at American College of Surgeons accredited ATC, PTC, and combined ATC/PTC trauma centers were evaluated. The primary outcome was operative management. Secondary outcomes include length of stay, and in-hospital complications. Multivariate logistical regression adjusting for race, sex, and insurance type will be performed. RESULTS/ANTICIPATED RESULTS: 40,111 children were treated for SOI from 2010-2018. 39.3% were treated at an ATC and 26.4% at a PTC. Of children treated at an ATC, 62% were White, 17% were Black, and 1% were Asian. Children treated at the PTC were 60% White, 20% Black, and 0.9% Asian. Primary insurance type was Medicaid for 33% of patients at an ATC and 39% at PTC. Median length of stay at ATC and PTC was 4 days (2-7) and 3 days (2-6) respectively. 3.85% of patients at ATC underwent splenectomy compared to 0.8% at PTC. It is anticipated that further analysis will demonstrate that ICU admission, transfusion, embolectomy, and other operative interventions will be more prevalent at ATC than MTC. Moreover, we anticipate that multivariate logistical regression will show the odds of receiving operative management at each center differ by race, sex and insurance type. DISCUSSION/SIGNIFICANCE: Initial analysis of the NTDB from 2010-2018 shows that children treated for SOI at ATC receive operative interventions more often than those treated at PTC. Elucidating disparities in SOI care is an important step towards minimizing the impact of these disparities and better allocating resources such that they may be eliminated.

OBJECTIVES/GOALS: In 2022, Chicago created the COVID-19 Response Corps, a cohort of community health workers (CHWs), trained to conduct contact tracing and vaccine outreach. Through an Earn and Learn program, corps members studied community-engaged participatory research, and co-led a rapid assessment with researchers to assess vaccine hesitancy in communities. METHODS/STUDY POPULATION: The Chicago COVID-19 Community Response corps worked to mitigate COVID-19 transmission in disadvantaged neighborhoods by activating CHWs, a diverse public health workforce from communities most affected by health and economic inequities. The Earn and Learn Program allotted 600 corps members up to 7.5 hrs/week of paid capacity building opportunities to learn new skills, pursue training programs, or college courses. Embodying a praxis of participatory action research and intergenerational organizing, corps members co-designed research questions and survey instruments, pilot tested the tools, trained other corps members on how to recruit and collect data, and contributed to the analysis and interpretation of the results. They generated evidenced-informed solutions to address future real-world problems. RESULTS/ANTICIPATED RESULTS: Corps members brought insight, cultural literacy, and lived experience that was invaluable in reaching the priority population of unvaccinated Chicagoans. They enhanced all aspects of the rapid assessment while conducting their work safely and comfortably in neighborhoods that outsiders consider challenging. Community member responses as to why they had not yet received a COVID-19 vaccine included being unable to risk putting what they saw as a rushed or improperly tested product into their bodies, to not being able to risk becoming ill even temporarily due to the potential for lost wages, as well as having other priorities in their lives which took precedence over concern about COVID-19, such as paying bills and feeding their families. DISCUSSION/SIGNIFICANCE: Research and evaluation benefits from the inclusion of CHWs. They are agile agents of change with the potential to replenish and repair trust in a fractured public health system. Engaging CHWs in evaluation work can strengthen community-academic partnerships and enhance the understanding of challenges and solutions to improving community health.

OBJECTIVES/GOALS: To describe the creation, use and outcome of a successful multi-session case study for team science education and training. Creating a case study that spans multiple sessions can aid in emphasizing many team science concepts using one ongoing scenario. METHODS/STUDY POPULATION: We will describe the creation and use of a multi-session case study used in a team science graduate course. This case study incorporates the interpretation and use of assessments that coincide with concepts presented in each session. Participants engage with the case study as a team. The use of this case study allows participants to draw conclusions and make decisions about team interventions using concepts they’ve just learned. The multi-session case study also allows participants to see the outcome of their decisions in the next session. Further, the continuous nature of this case study allows participants to build on their knowledge from session to session and make connections between concepts. RESULTS/ANTICIPATED RESULTS: Incorporating a multi-session case study should help participants better understand team science concepts and practice incorporating the use of those concepts into teams in a more realistic way over time. The case study framework has been used in a team science graduate course for the last two years. The teaching team has incorporated continuous improvement into optimizing the case study over time. We’ll share preliminary results collected over the use of the case study so far along with the improvements made over time. DISCUSSION/SIGNIFICANCE: This education framework is very versatile and can be incorporated into a team science course or series of workshops and provides a real-world situation that allows participants to practice incorporating team science concepts and interventions in a team.

OBJECTIVES/GOALS: Our objective is to develop a Telenephrology dashboard for the 150,000 Veterans that obtain care through the Iowa City Veterans Affairs Health Care System. Our goal is to create a comprehensive and user-friendly tool for monitoring kidney health and facilitating remote nephrology consultations. METHODS/STUDY POPULATION: We structured our intervention according to the five stages of human-centered design: (1) Empathize, (2) Define, (3) Ideate, (4) Prototype and (5) Test. During the empathy stage, the principal investigator spent 10 hours immersed in the clinical setting observing how nephrologists approach a remote nephrology consultation. These observations were augmented by unstructured interviews with clinicians and patients to better understand the process and dynamics. Following this, a rapid ideation workshop was convened to generate creative solutions that balance technical requirements with the needs of clinicians and patients. These led to rapid prototyping and testing to identify what elements of the prototypes worked and which needed improvement. RESULTS/ANTICIPATED RESULTS: Through the empathy and define stages, three needs were identified: (1) clarity in visualizing data, (2) accuracy of information, and (3) balancing standardization with individualization. During the rapid ideation workshop, the concept of a four-frame dashboard was settled upon. This led to the creation of five prototypes, which were tested. These were reconciled and modified to make a final product. This final product, the Telenephrology Dashboard, contains 5 elements that support nephrologists and supporting staff: (1) a graph of kidney function over time, (2) tables synthesizing lab data, (3) options to drill down events to specific times, (4) customization of views, and (5) integration of kidney disease progression models. DISCUSSION/SIGNIFICANCE: A Telenephrology dashboard was created to facilitate remote nephrology consultations through a Human-Centered Design process. Our next steps include determining if this dashboard may improve end-user satisfaction, referring clinician satisfaction, access to specialist care, and patient outcomes.

OBJECTIVES/GOALS: Chronic kidney disease (CKD) affects nearly 40% of adults with diabetes. Our objective is to assess trends in risk factor control and use of 2022 ADA and KDIGO guideline-recommended medications. METHODS/STUDY POPULATION: Using data from 1988 to 2020 from the National Health and Nutrition Examination Survey, we will examine trends in sociodemographic risk factors and glycemic, blood pressure, and lipid control among adults with CKD and diabetes. Glycemic control will be defined as a hemoglobin A1c (HbA1c)<7%, blood pressure control will be examined at cutoffs of 130/80 and 120/80 mmHg, and lipid control will be defined as a fasting triglyceride level ≥150 mg/dL, a low-density lipoprotein (LDL) <100 mg/dL without atherosclerotic cardiovascular disease (ASCVD), or LDL<70 mg/dL if they have ASCVD. We will assess changes in the use of commonly used antidiabetic, antihypertensive, and lipid-lowering medications. RESULTS/ANTICIPATED RESULTS: We hypothesize that from 1988-2020, blood pressure control has improved while glycemic and lipid control has not improved among adults with diabetes and CKD. We expect decreases in sulfonylurea use and increases in DPP-4 inhibitor, metformin, ACE inhibitor, angiotensin receptor blocker, statin, and insulin use over time among those with diabetes and CKD. In addition, there is likely a significant gap between those who are eligible to use newer medications like SGLT2 inhibitors or GLP-1 receptor agonists and who are currently using them within this subpopulation. DISCUSSION/SIGNIFICANCE: This study will examine adherence to guideline-recommended management and identify gaps in care for adults with CKD and diabetes, which may inform how best to optimize medication use for cardiorenal protection in this high-risk patient population.

OBJECTIVES/GOALS: Social isolation/loneliness is a public health crisis and one that is unlikely to be solved through pharmacology. Nonpharmacological approaches, such as dance, are needed. The objective of this study is to investigate the physiological correlates of dance-induced improvements in social connection. METHODS/STUDY POPULATION: Participants were randomly assigned to participate for 4 weeks (2 times per week, 90-minute sessions) in either 1) improvisational dance training (experimental group; n=7); or a 2) dance movie watching experience (control group; n=7). Before and after the intervention, using mobile brain-body imaging techniques, participants and their instructor had their brain (via electroencephalography) and body physiology (via photoplethysmography) recorded during a series of verbal and nonverbal interactive experiences. Participants were also video recorded via 4 surrounding cameras for later motion capture analysis. Neuropsychological assessments were also conducted before and after the intervention. RESULTS/ANTICIPATED RESULTS: We found that dance significantly increased social skills including empathy, interpersonal skills, emotional regulation, mindfulness, and attention. Additionally, we found that dance significantly increased interbrain synchrony during nonverbal experiences including theta (4-8 Hz), beta (12-35 Hz), and gamma (35-45 Hz) frequencies in the occipital lobe. Increases in interbrain synchrony were also positively correlated with increases in empathy. Additionally, intercardiac synchrony between the participant and instructor showed a significant correlation at post-intervention only. Future investigations will focus on the relationship between interbrain, intercardiac, and movement synchrony. DISCUSSION/SIGNIFICANCE: Our findings support the idea that dance increases interpersonal synchrony at the level of the brain, heart, and behavior. Understanding the neural and somatic mechanisms of social behaviors will help promote understanding and development of interventions for the critical problem of social isolation and loneliness.

OBJECTIVES/GOALS: Contingency management (CM) procedures yield measurable reductions in cocaine use. This poster describes a trial aimed at using CM as a vehicle to show the biopsychosocial health benefits of reduced use, rather than total abstinence, the currently accepted metric for treatment efficacy. METHODS/STUDY POPULATION: In this 12-week, randomized controlled trial, CM was used to reduce cocaine use and evaluate associated improvements in cardiovascular, immune, and psychosocial well-being. Adults aged 18 and older who sought treatment for cocaine use (N=127) were randomized into three groups in a 1:1:1 ratio: High Value ($55) or Low Value ($13) CM incentives for cocaine-negative urine samples or a non-contingent control group. They completed outpatient sessions three days per week across the 12-week intervention period, totaling 36 clinic visits and four post-treatment follow-up visits. During each visit, participants provided observed urine samples and completed several assays of biopsychosocial health. RESULTS/ANTICIPATED RESULTS: Preliminary findings from generalized linear mixed effect modeling demonstrate the feasibility of the CM platform. Abstinence rates from cocaine use were significantly greater in the High Value group (47% negative; OR = 2.80; p = 0.01) relative to the Low Value (23% negative) and Control groups (24% negative;). In the planned primary analysis, the level of cocaine use reduction based on cocaine-negative urine samples will serve as the primary predictor of cardiovascular (e.g., endothelin-1 levels), immune (e.g., IL-10 levels) and psychosocial (e.g., Addiction Severity Index) outcomes using results from the fitted models. DISCUSSION/SIGNIFICANCE: This research will advance the field by prospectively and comprehensively demonstrating the beneficial effects of reduced cocaine use. These outcomes can, in turn, support the adoption of reduced cocaine use as a viable alternative endpoint in cocaine treatment trials.

OBJECTIVES/GOALS: Community-based residency programs often lack formal training in research scholarship required by ACGME. To address this need, UCSF’s CTSI collaborated with residency leaders to implement a self-paced online curriculum for residents called Training in Practice Based Research (TIPR). We describe characteristics of the initial trainee cohort. METHODS/STUDY POPULATION: In the 2022-23 academic year, TIPR was offered to 10 UCSF-affiliated family medicine residency programs across Northern California and the Central Valley, and 8 chose to participate. An additional community-based psychiatry residency independently contacted our team and was also granted permission to participate. We conducted baseline surveys with participants to understand their prior research experience and motivation to join TIPR. Descriptive data for demographics of trainees and their prior research experience were collected using Qualtrics. Thematic analyses were conducted on qualitative responses. RESULTS/ANTICIPATED RESULTS: Of 32 participants, 29 completed the survey (91%). Learners identified as 40% non-Hispanic White, 28% Asian, 16% Hispanic, 9% non-Hispanic Black, and 15% non-Hispanic other. 28% were motivated to participate in the program because it was a residency requirement, 31% wanted to improve their scholarly skills and confidence, 16% were interested in career development, and 6% were interested in networking. 19% reported no research experience. Participants are currently working on scholarly projects designed during the first year of TIPR. In 2023-2024, with the addition of two new family medicine residency programs, an additional 40 residents have enrolled in TIPR. In April 2024, we will present data on projects completed, and demographics of the full cohort. DISCUSSION/SIGNIFICANCE: With CTSI support, TIPR has reached a large cohort of ethnically diverse physician trainees in community-based settings. Future evaluation will focus on whether TIPR increases the quantity and quality of practice-based research within residency training programs served by this program.

OBJECTIVES/GOALS: Participating in out-of-school activities (i.e., sports) is associated with improved physical and mental health, but racial/ethnic and income disparities persist. Our goal was to describe parent perspectives to understand how to enhance family engagement in these activities, especially in low-income Black and Latinx communities. METHODS/STUDY POPULATION: We recruited parents through a large urban parks and recreation department located in Los Angeles County (LAC) and two community-based organizations who provide services primarily to low-income Black and Latinx residents in LAC. We conducted semi-structed English or Spanish interviews with parents of children ages 6-17 about the impact of activities on families, experiences making it difficult or easier for their child to be involved, and recommendations to meet their needs and facilitate family engagement. We coded the interviews using Dedoose and then performed thematic analysis. RESULTS/ANTICIPATED RESULTS: We completed 34 interviews (17 English, 17 Spanish). Parents shared these central ideas about out-of-school activities: (1) they support families and promote healthy child development; (2) they must create a safe environment and promote a sense of belonging for all families; and (3) service delivery changes reduced barriers, but activities often remained inaccessible. Barriers included lack of awareness about low-cost options, online enrollment, financial costs, waitlists, program timing, inaccessible parks/pools, safety, inconsistent quality, few opportunities for families to participate together, and a desire for more inclusive practices around race, culture, language, gender, children with special needs, and parent involvement. Parents offered recommendations to increase family engagement. DISCUSSION/SIGNIFICANCE: Involving parents in optimizing out-of-school activities may improve access, uptake, and quality of these health-promoting activities in low-income Black and Latinx communities.

OBJECTIVES/GOALS: 48,000,000 people in the U.S. have hearing loss, negatively impacting quality of life and work. Unveiling axon guidance for auditory type II spiral ganglia neurons (SGNs) will aid development of new therapies. I study the role of Eph/Ephrin and planar cell polarity (PCP) signaling during type II SGN turning and outer hair cell (OHC) innervation. METHODS/STUDY POPULATION: This quantitative study was conducted on Efna3 and Vangl2 null mice possessing Neurog1CreERT2 and R26RtdTomato mutations. Spontaneous Cre activity within the Neurogenin1CreERT2 line causes recombination and expression of fluorescent Rosa26 Reporter (R26R)tdTomatoin a restricted number of SGNs, including type IIs. Together, these lines permit SGN sparse labeling. Immunostaining and confocal imaging were used to analyze dsRed in Efna3 and Vangl2 mice and quantify type II SGN turning. In combination, Imaris 3D renderings were used to quantify type II SGN turning, branching, navigation features and temporal effects of EPHRIN-A3-Fc on type IIs via cochlear cultures (a gain-of-function manipulation). For both sexes, 5-6 cochleae per genotype were analyzed and compared by t-test to wildtype (WT) controls. RESULTS/ANTICIPATED RESULTS: Efna3 nulls showed a small rise in type II SGNs incorrectly turning toward the apex at an error rate of 16.0% compared to WTs (n=6; p=0.05). P0 Efna3 nulls had reduced branch number compared to WTs, 4.1 and 7.2, respectively (n=129; p=<0.0001), suggesting EPHRIN-A3 acts as a positive growth cue. In cochlear cultures, EPHRIN-A3-Fc led to type II SGN collapse at E15.5, indicating a repulsive function. However, at P0, EPHRIN-A3-Fc treatment led to type II SGNs with elevated branch numbers compared to Control-Fc treatment: 18.1 and 11.4, respectively (n=116; p=<0.0001). This indicates a positive growth function. At E16.5, EPHRIN-A3 protein immunoreactivity on Deiters’ and pillar cells appears reduced in Vangl2 nulls compared to WT cochleae, suggesting that EPHRIN-A3 acts downstream of PCP signaling. DISCUSSION/SIGNIFICANCE: Results suggest that Eph/Ephrin signaling acts downstream of PCP signaling to mediate type II SGN guidance and EPHRIN-A3 switches its mode of activation. The clinical implications of these findings are that therapeutics targeting EPHRIN-A3 and/or VANGL2 in their given pathways could stimulate new OHC innervation following auditory damage.