OBJECTIVES/SPECIFIC AIMS: MDSCs are potent suppressors of T cell function, and have been recently found to be implicated in skin diseases driven by T cell dysregulation. However, the function of MDSCs in CLE is poorly understood. We sought to characterize the MDSC population in the peripheral blood of DLE patients and evaluate their ability to suppress autologous T cells. METHODS/STUDY POPULATION: All patients were recruited through the UT Southwestern Cutaneous Lupus Registry. PBMCs from 32 CLE patients and 16 age-matched and gender-matched controls were analyzed using flow cytometry. Monocytic MDSCs were identified by the phenotype of CD14+ HLA-DR neg/low. Furthermore, autologous MDSCs and T cells were purified from CLE PBMCs (n=4) and co-cultured at different ratios of these cells. T cell function was measured by secretion of IFN-γ by ELISA. RESULTS/ANTICIPATED RESULTS: Monocytic MDSCs in CLE PBMCs (median: 2.04%, IQR: 0.67%–5.07%) were significantly higher compared with healthy control PBMCs (median: 0.5%, IQR: 0.1%–1.07%, p=0.002). Although not significant on subset analysis, patients with CLE limited to the head and neck had the highest levels of MDSCs. CLE MDSCs (n=4) were found to suppress autologous activated T-cells in a dose-dependent manner. DISCUSSION/SIGNIFICANCE OF IMPACT: In this cross-sectional study of patients of the UT Southwestern Cutaneous Lupus Registry, we observed differences in the levels of MDSCs among PBMCs of CLE patients Versus healthy controls. CLE patients had significantly higher levels of MDSCs, which could be explained by the presence of an inflammatory state in this group. Furthermore, CLE MDSCs were able to suppress autologous T cells, showing that these cells are functionally patent in CLE blood. Their up-regulation in CLE blood may represent the body’s response to limiting disease severity, since most patients had mild disease activity.

ABSTRACT IMPACT: Circadian disruption is known to cause significant human pathology but has not been evaluated in pancreas cancer carcinogenesis; through understanding how disruption of circadian rhythms can lead to pancreas cancer development and spread, preventive and therapeutic strategies can be devised. OBJECTIVES/GOALS: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer due to early spread and poor response to therapy. Identifying factors driving PDAC growth could lead to new therapeutic strategies. Thus, we evaluated the extent to which circadian rhythm disruption, a factor strongly associated with cancer formation, contributes to PDAC pathogenesis. METHODS/STUDY POPULATION: To achieve the objective, we evaluated mice with pancreas lineage Kras-mutation (KC mice), which are predisposed to develop the full spectrum of pancreas cancer precursor lesions (pancreatic intra-epithelial neoplasia or PANIN-1, 2, 3) and PDAC. We subjected KC mice to a light-dark phase shift protocol known to induce circadian disruption (KCCD, n = 18), and another group to standard lighting conditions (KCNC, n = 31), with equal numbers of males and females in each group. The mice were allowed access to food and water ad libitum until sacrifice at age 9 months. Histopathologic evaluation of the pancreas was then performed to assess for pancreatic inflammation, pancreatic precursor lesions (PANIN) and PDAC. Fisher’s Exact Test was used to evaluate differences in incidence. RESULTS/ANTICIPATED RESULTS: As expected, both groups of mice demonstrated 100% incidence of chronic pancreatitis and PANIN-1 (low-grade precursor lesion) at age 9 months. This is consistent with the KC phenotype. However, the KCCD mice demonstrated a significant increase in acute pancreatic inflammation (61.1% vs 19.4%, p = 0.005) compared to KCNC mice. Furthermore, intermediate grade precursor lesions (PANIN-2) were also significantly increase in the KCCD mice (38.9% vs 6.5%, p = 0.006). Incidence of high-grade precursor lesions (PANIN-3, or carcinoma in situ: 22.2% vs 9.7%) and PDAC (27% vs 19%) were also increased, but these were not statistically significant. These results are notable given the established progression from higher grade premalignant PANIN lesions (PANIN-2, PANIN-3) to PDAC. DISCUSSION/SIGNIFICANCE OF FINDINGS: Insight into how circadian disruption leads to increased PANIN-2 formation and increase in acute inflammation may be advantageous for understanding circadian disruption in PDAC carcinogenesis. The circadian clock is present in immune cells and disruption can induce immune dysregulation. This mechanism will be evaluated in follow up studies.

OBJECTIVES/SPECIFIC AIMS: Obstructive lung disease following particulate matter (PM) exposure is a major health concern. Coexisting metabolic syndrome (MetSyn) often occurs. Receptor for advanced glycation end products (RAGE) is highly expressed in the lung, is a strong predictor of FEV1, and is a key mediator of MetSyn. To determine if the loss of RAGE protects from the persistence of effects of particulate associated lung injury in a murine model. METHODS/STUDY POPULATION: Wild type (WT) and RAGE knockout (RKO) mice were exposed to 100 μg of PM (WTC-Aggregate, PM53) or PBS control by oropharyngeal aspiration. Lung function, methacholine challenge, and bronchoalveolar lavage (BAL) were quantified 28 days after PM exposure using flexiVent (Scireq Montreal, QC). BAL was obtained and cell differentials, cytokines and transcription factors were assayed. Bio-volume to airspace ratio and mean chord length were measured (Image J and Adobe Photoshop). RESULTS/ANTICIPATED RESULTS: WT mice were hyper-reactive to methacholine compared with their PBS controls 28 days after a single exposure to PM. They recovered from increased neutrophilia, loss of FEV, decreased compliance, and increased resistance, which were previously observed 24-hours after exposure. RKO were not hyper-reactive when compared with their own PBS controls. Lung histology shows persistence of loss of alveolar space in WT mice exposed to PM after 28 days. Area fraction was significantly higher in PM exposed WT mice after 28 days which was not significant after 24 hours. Mean chord length was significantly shorter for PM exposed at both time points for WT mice. The relative expression of phosphorylated to total CREB and ERK1/2 proteins was lower in RKO PM exposed mice compared with WT PM while STAT3 expression was lower in WT PM compared with WT PBS. PM induced a lower fold change of total proteins from the PBS controls in RKO for CREB, p38, ERK1/2, STAT3, and STAT5. JNK and p70S6k total proteins expressed a decreased fold change in WT PM exposed mice compared with WT PBS controls. DISCUSSION/SIGNIFICANCE OF IMPACT: A single dose of PM can produce persistent airway hyper-reactivity after 28 days of exposure. This PM induced injury is alleviated in the absence of RAGE, similar to what was seen at 24 hours. Inhibiting RAGE may be key to limiting the persistent inflammatory effects of high intensity PM exposure.

OBJECTIVES/GOALS: Our concept of reciprocal innovation (RI) supports global health (GH) research partnerships that address shared health challenges for mutual benefit in both high and low- and middle-income (LMIC) settings. To advance this GH approach, the Indiana CTSI launched a RI program building on longstanding global health partnerships in East Africa METHODS/STUDY POPULATION: A core component of the program is annual RI workshops to promote reciprocal approaches in GH, identify priority areas for reciprocal research, and link investigators and stakeholders across settings. The first meeting in 2019 was in-person and focused on identifying health priority areas from the perspective of Indiana stakeholders. The second meeting was held virtually and focused on priority areas in East Africa. The third meeting focused on shared priority areas and discussing potential RI research projects. Agenda sessions include (1) presenting successful examples of funded RI projects; (2) breakout groups to share proposal ideas in preparation for the RI grants program; (3) building partnerships with colleagues in similar fields RESULTS/ANTICIPATED RESULTS: As of 2021, three RI workshops have been held with an average of 60 attendees at each workshop. Participants identified several overlapping priority areas for research and RI in Indiana and East Africa, including research in chronic disease, substance abuse, infant and maternal health, and access to healthcare. A Global Health Innovation Exchange of RI projects was created to support connections between locally- and globally-focused investigators. The repository is used to share updates on project progress, outcomes, and published materials. Workshops have also been used to explore a reciprocal innovation virtual platform to facilitate and foster more regular collaborations between globally and locally-focused investigators and pursue research projects on shared health challenges for mutual benefit DISCUSSION/SIGNIFICANCE: The collaboration at the stakeholder meetings set the foundation for continued partnership building, strong proposals for RI grants, and dissemination and translation of successful RI projects. To leverage momentum from the meetings, we are building a virtual RI platform to connect PIs across multiple CTSAs and increase the footprint of RI efforts

OBJECTIVES/GOALS: The glucocorticoid receptor (GR) is a ubiquitous steroid hormone receptor that is emerging as a mediator of breast cancer metastasis. We aim to better understand the biology associated with phospho-GR species in TNBC and their contribution to tumor progression. METHODS/STUDY POPULATION: To better understand how p-S134 GR may impact TNBC cell biology, we probed GR regulation by soluble factors that are rich within the tumor microenvironment (TME), such as TGFβ. TNBC cells harboring endogenous wild-type or S134A-GR species were created by CRISPR/Cas knock-in and subjected to in vitro assays of advanced cancer behavior. RNA-Seq was employed to identify pS134-GR target genes that are uniquely regulated by TGFβ in the absence of exogenously added GR ligands. Direct regulation of selected TGFβ-induced pS134-GR target genes was validated accordingly. Bioinformatics tools were used to probe publicly available TNBC patient data sets for expression of a pS134-GR 24-gene signature. RESULTS/ANTICIPATED RESULTS: In the absence of GR ligands, GR is transcriptionally activated via p38-MAPK-dependent phosphorylation of Ser134 upon exposure of TNBC cells to TME-derived agents (TGFβ, HGF). The ligand-independent pS134-GR transcriptome primarily encompasses gene sets associated with TNBC cell survival and migration/invasion. Accordingly, pS134-GR was essential for TGFβ-induced TNBC cell migration, anchorage-independent growth in soft-agar, and tumorsphere formation, an in vitro readout of breast cancer stemness properties. Finally, a 24-gene pSer134-GR-dependent signature induced by TGFβ1 predicts shortened survival in breast cancer. We expect to find similar results using an in-house tissue microarray. DISCUSSION/SIGNIFICANCE OF IMPACT: Phospho-S134-GR is a critical downstream mediator of p38 MAPK signaling and TNBC migration, survival, and stemness properties. Our studies define GR as a required effector of TGFβ1 signaling and nominate pS134-GR as a biomarker of elevated risk of breast cancer dissemination.

Objectives/Goals: The objective of this study is to explore strategies for AI-physician collaboration in diagnosing acute respiratory distress syndrome (ARDS) using chest X-rays. By comparing the diagnostic accuracy of different AI deployment methods, the study aims to identify optimal strategies that leverage both AI and physician expertise to improve outcomes. Methods/Study Population: The study analyzed 414 frontal chest X-rays from 115 patients hospitalized between August 15 and October 2, 2017, at the University of Michigan. Each X-ray was reviewed by six physicians for ARDS presence and diagnostic confidence. We developed a deep learning AI model for detecting ARDS and explored the strengths, weaknesses, and blind spots of both physicians and AI systems to inform optimal system deployment. We then investigated several AI-physician collaboration strategies, including: 1) AI-aided physician: physicians interpret chest X-rays first and defer to the AI model if uncertain, 2) physician-aided AI: the AI model interprets chest X-rays first and defers to a physician if uncertain, and 3) AI model and physician interpreting chest X-rays separately and then averaging their interpretations. Results/Anticipated Results: While the AI model (84.7% accuracy) had higher accuracy than physicians (80.8%), we found evidence that AI and physician expertise are complementary. When physicians lacked confidence in a chest X-ray’s interpretation, the AI model had higher accuracy. Conversely, in cases of AI uncertainty, physicians were more accurate. The AI excelled with easier cases, while physicians were better with difficult cases, defined as those where at least two physicians disagreed with the majority label. Collaboration strategies tested include AI-aided physician (82.4%), physician-aided AI (86.9%), and averaging interpretations (86%). The physician-aided AI approach had the highest accuracy, could off-load the human expert workload on the reading of up to 79% chest X-rays, allowing physicians to focus on challenging cases. Discussion/Significance of Impact: This study shows AI and physicians complement each other in ARDS diagnosis, improving accuracy when combined. A physician-aided AI strategy, where the AI defers to physicians when uncertain, proved most effective. Implementing AI-physician collaborations in clinical settings could enhance ARDS care, especially in low-resource environments.

OBJECTIVES/GOALS: The project investigates the role that resiliency may play within individual, interpersonal, social, and structural contexts in protecting against acute lethal stimulant (meth/amphetamine or cocaine) toxicity. Identifying preventative factors is crucial in developing and implementing risk reduction strategies for people who use stimulants. METHODS/STUDY POPULATION: This is a qualitative study involving in-depth interviews via questionnaire assessing resiliency factors among persons living in San Francisco who have used primarily either meth/amphetamine or cocaine for at least 5 years. The interviews will be coded for salient and recurrent themes and analyzed for code frequency, cooccurrences, clustering of themes and representative excerpts to highlight emergent themes as well as stressors and resilience factors at multiple levels. We aim to assess for substance use patterns, multiple domains of resiliency, medical and psychiatric complaints, and risk reduction strategies. We will recruit participants to match recent decedents from acute stimulant toxicity in various domains including salient demographic information and neighborhood characteristics. RESULTS/ANTICIPATED RESULTS: The anticipated results include a qualitative interview guide for living persons using stimulants in San Francisco to be used to gain insight into the community, illustrate participants’ substance use practices, and allow for better characterization of several discrete resiliency factors that have protected the participants and other community members from suffering lethal stimulant toxicity. We expect to identify individual components (e.g. use patterns, use of harm reduction supplies), interpersonal/social factors (e.g. drug using network, friendships, community connection), and structural influences (e.g. access to care, safe use sites, house and economic stability) that all play a role in resiliency against lethal stimulant toxicity. DISCUSSION/SIGNIFICANCE: Stimulant use is common, along with rising deaths involving stimulants in urban counties and in smaller rural/non-metro counties which are disproportionately affected, posing a public health challenge. We will find discrete, modifiable risk and resiliency factors that can be manipulated to minimize the chances of outcomes like overdose and death.

Multi-site and multi-organizational teams are increasingly common in epidemiologic research; however, there is a lack of standards or best practices for achieving success in collaborative research networks in epidemiology. We summarize our experiences and lessons learned from the Diabetes Location, Environmental Attributes, and Disparities (LEAD) Network, a collaborative agreement between the Centers for Disease Control and Prevention and research teams at Drexel University, New York University, Johns Hopkins University and Geisinger, and the University of Alabama at Birmingham. We present a roadmap for success in collaborative epidemiologic research, with recommendations focused on the following areas to maximize efficiency and success in collaborative research agreements: 1) operational and administrative considerations; 2) data access and sharing of sensitive data; 3) aligning network research aims; 4) harmonization of methods and measures; and 5) dissemination of findings. Future collaborations can be informed by our experiences and ultimately dedicate more resources to achieving scientific aims and efficiently disseminating scientific work products.

The COVID-19 pandemic had an immediate impact on the lives and work of early-career researchers. We leveraged a cluster-randomized trial and compared survey data collected over two timepoints to explore whether these impacts persisted. Although more than a year had passed, 74% of participants reported that their research was affected in multiple ways in both 2020 and 2021. These data suggest that the effects of the pandemic on early-career researchers may be prolonged. Our findings additionally serve as an impetus to identify and implement solutions to early-career challenges that undoubtedly existed before the pandemic, but which COVID-19 brought into the spotlight.

In recent times, there have been calls from within the developing nations for increased ownership by governmental research bodies and universities of the priority research setting and research that aligns with national health strategies. This is a review paper of the studies that have been published on clinical trials in developing countries, with a focus mainly on Pakistan. The literature review used online databases such as PubMed, Scopus, and Google Scholar, World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov trial registries to search for clinical trials conducted in Pakistan between January 2000 and December 2022 and analyzed. The results revealed that clinical research in Pakistan is hindered by a number of barriers, including a lack of funding, skilled personnel, and regulatory issues. Lack of funding is a common obstacle, and the majority of funding for clinical trials originates from Western countries or pharmaceutical companies established in the West. In conclusion, clinical studies in developing countries, especially in Pakistan, are hindered by a plethora of barriers, and to improve the current state, increasing funding, streamlining ethical approval procedures, simplifying regulatory systems, addressing cultural and religious concerns, and participating in global efforts to bridge the gap in health-based research are crucial.

OBJECTIVES/SPECIFIC AIMS: A brain-machine interface (BMI) is a device implanted into the brain of a paralyzed or injured patient to control an external assistive device, such as a cursor on a computer screen, a motorized wheelchair, or a robotic limb. We hypothesize we can utilize electrical stimulation of subdural electrocorticography (ECoG) electrodes as a method of generating the percepts of somatosensation such as vibration, temperature, or proprioception. METHODS/STUDY POPULATION: There will be 10 subjects, who are informed, willing, and consented epilepsy patients undergoing initial surgery for placement of subdural ECoG electrodes in the brain for seizure monitoring. ECoG will be used as a platform for recording high-resolution local field potentials during real-touch behavioral tasks. In addition, ECoG will also be used to electrically stimulate the human cerebral cortex in order to map and understand how varying stimulation parameters produce percepts of sensation. RESULTS/ANTICIPATED RESULTS: To determine how tactile and proprioceptive signals are integrated in S1, we will perform spectral analysis of the broadband local field potentials to look for increased power in specific frequency bands in the ECoG recordings while touching or moving the hand. To explore generating artificial sensation, the subject will be asked to perform a variety of tasks with and without the aid of stimulation. We anticipate the subject’s performance will be enhanced with the addition of artificial sensation. DISCUSSION/SIGNIFICANCE OF IMPACT: Many patients might benefit from a BMI, such as those with stroke, amputation, spinal cord injury, or brain trauma. The current generation of BMI devices are guided by visual feedback alone. However, without somatosensory feedback, even the most basic limb movements are difficult to perform in a fluid and natural manner. The results from this project will be crucial to developing a closed loop motor/sensory BMI.

Objectives/Goals: This study aimed to enhance clinical trial data management through large language model information retrieval and generation techniques within the clinical trial reporting workflow. We focused on improving compliance with reporting, reducing human labor, and promoting standardized reporting structure and data quality oversight. Methods/Study Population: We used approved study protocols from UC Davis IRB-approved investigator-initiated studies compared to the same studies reported to ClinicalTrials.gov. Our baseline data extraction system employs commercial large language models (LLMs) and retrieval augmented generation (RAG) to isolate data sources within the secure extraction environment. We stratified protocol documents into easy, complex, and random categories based on study focus, document complexity, the extent of amendments or modifications, and completion metrics from ClinicalTrials.gov. We developed a pilot web-based architecture to capture variations in categorization, labeling, and reporting style and compared generated extraction data. We primarily focused on qualitative evaluation through a review of expert staff. Results/Anticipated Results: Our results revealed significant variations in reporting quality, with dependencies stemming from multiple authors and stages throughout the clinical trial protocol lifecycle. Based on these variations, we used prompt engineering to improve the pilot application’s output compliance with the protocol registration and results system (PRS) structured data format for various study types. We piloted the assisted workflow with prospective studies by partnering with study investigators and the clinical trial office staff to assist in review and clinical trial reporting creation. Initial studies reported by our system were approved and released to the public by PRS staff. We are refining content generation and workflows to different components of studies and evaluating their use in quality and training areas. Discussion/Significance of Impact: Our system fosters collaboration, efficient review, and compliance with clinical trial reporting standards. It supports the promise of AI-driven assistance in clinical trial management, design, and reporting. We focus on the multiple stakeholders, expertise, and data flows in the organizational management of clinical and translational science.

OBJECTIVES/GOALS: To increase vaccination rates in Black and Latino communities, specifically in South LA and the Eastside of LA. METHODS/STUDY POPULATION: Multimedia campaign combined with vaccine navigation and assistance, led by the SC CTSI and conducted by an interdisciplinary team from 14 schools at USC and CHLA, >160 community partners. RESULTS/ANTICIPATED RESULTS: VaccinateLA was a highly interdisciplinary and multifaceted project that demonstrated increased vaccination rates in Black and Latino communities in South LA and Eastern part of LA. We vaccinated over 1000 people, facilitated vaccines for almost 10k people and reached 1.37M people through our digital campaign. DISCUSSION/SIGNIFICANCE: We have used community vaccine navigators, pop-up clinics, narrative storytelling and other unique approaches to encourage vaccine uptake in communities of color. We plan to expand activities to parents and children in these communities, encourage booster uptake, and evaluate and disseminate the program widely.

OBJECTIVES/GOALS: In this study, we established a high-throughput chemical screening platform to identify small molecules that facilitates efficient differentiation of stem cells derived β (SC-β) cells. Using this platform, we identified several compounds that potentially increase the differentiation efficiency. METHODS/STUDY POPULATION: Differentiation of human embryonic stem cells (HUES8) into SC-β was carried out using previously published protocols in a 3D cell suspension. Single cells were replated in Matrigel-coated well plates at the start of different stages depending on experiments. Differentiation medium supplemented with small molecules at a final concentration of 2 M and 0.2 M was used throughout the stage. All the cells were then fixed and permeabilized. Immunocytochemical staining was performed. Images of each well were taken and analyzed. Numbers of the total cell, insulin-positive cell, NKX6.1-positive cell, and co-positive cell were recorded. Candidate compounds were validated using flow cytometry or ICC. RESULTS/ANTICIPATED RESULTS: We identified several hit compounds that significantly increase the NKX6.1 positive cell percentage compared to the DMSO-treated controls when treated at the PP1 cell stage. Follow up assays demonstrated that at least one of these putative hits reproducibly increased NKX6.1 expression. In addition, we identified other compounds that significantly increase the insulin and NKX6.1 copositive SC-β cell population when treated at the later PP2 cell stage during the differentiation. We expect a dosage-dependent response when the candidate hits are validated using more accurate assays. DISCUSSION/SIGNIFICANCE OF IMPACT: We established a high-throughput screening platform to identify small molecules that increase the efficiency of SC-β direct differentiation. Successful generation of SC-β allows cell replacement therapy in diabetes patients, and a better understanding of pancreatic biology and development.

OBJECTIVES/SPECIFIC AIMS: The goal of the present study was to advance our understanding of how alcohol use may contribute to physical inactivity among university students by investigating this association at a day-to-day level. METHODS/STUDY POPULATION: In total, 57 university students (Mage=20.27; 54% male) completed daily diary questionnaires using a cellphone application, which prompted them each evening to report minutes of moderate/vigorous physical activity engaged in, and number of alcoholic drinks consumed, as well as intended minutes of physical activity for the following day. Longitudinal mixed-level modeling was used to disentangle within person and between-person effects of alcohol use on physical activity behavior and intentions. Separate models were run to investigate lagged effects of previous day alcohol use. We controlled for sex and age in all models. RESULTS/ANTICIPATED RESULTS: Results indicated that participants’ usual alcohol use (between-person) was not associated with physical activity behavior or intentions. At the within-person level, day-to-day variance in alcohol use was negatively associated with both physical activity behavior (γ=−0.34, p=0.003) and intentions to engage in physical activity the following day (γ=−0.70, p<0.001). The lagged model indicated that previous day alcohol use negatively predicted PA behavior (γ=−0.33, p=0.004). DISCUSSION/SIGNIFICANCE OF IMPACT: Previous studies have largely been constrained to cross-sectional designs, and have surmised that there exists a positive association between alcohol use and physical activity due to trait-level differences between university students. We advance this literature by using ecological momentary assessment to investigate the within-person effects of alcohol use on physical activity at a day-to-day level while controlling for between-person variance. Contrary to existing literature, we found that on days when students consumed relatively more alcohol than they typically report, they: (a) report fewer minutes of physical activity on the same day, (b) plan to engage in relatively less physical activity on the subsequent day, and (c) engage in less physical activity on the subsequent day. By advancing our understanding of how alcohol use may curtail other health behaviors such as physical activity, we inform interventions that aim to target these behaviors in conjunction, or as part of a multiple behavior change intervention.

OBJECTIVES/GOALS: The rapid spread of Monkeypox (MPV) across the US may trigger stress reactions that increase the risk of developing secondary trauma among those most at risk of exposure. The present study aimed to investigate the degree to which vicarious MPV exposure (i.e., knowing people who acquired MPV), was associated with symptoms of secondary traumatization. METHODS/STUDY POPULATION: An online survey was administered to 253 participants enrolled in Keeping it LITE, a prospective U.S. cohort study of ethnically diverse, sexually active, sexual, and gender minority persons aged 19–39 in September 2022. Multiple linear regression was used to examine the association between proximity to MPV and secondary traumatic stress (STS) symptoms. RESULTS/ANTICIPATED RESULTS: Study findings demonstrated that MPV morbidity was low (1%); however, 37% of participants reported knowing at least one person diagnosed with MPV. For most individuals, this person was a friend (28%). 16% of participants were found to have at least one indicator of MPV-related STS. Our multiple linear regression results demonstrated a positive association between an individual’s indirect exposure to MPV via their interpersonal relationships and STS symptoms. DISCUSSION/SIGNIFICANCE: Findings suggest that the more adults’interpersonal relationships are saturated with people who have acquired MPV, the more likely they are to develop symptoms of secondary traumatization. These findings provide initial evidence that secondary exposure to MPV via one’s social network may undermine adults’mental health.

OBJECTIVES/GOALS: In 2010, an estimated 65% of antipsychotic prescriptions were given to youth for off-label indications. It is unclear whether subsequent calls for reduced pediatric prescribing led to a decrease in off-label use. This study examined the diagnostic characteristics of the current pediatric population using antipsychotics in the United States. METHODS/STUDY POPULATION: Data from the Clinformatics Data Mart, a database containing longitudinal patient information between 2010-2019 from commercial healthcare insurance claims in the United States was used in this study. We conducted a case-control study, in which antipsychotic initiators were matched 1:1 to non-initiators on age, sex, and insurance enrollment. There were 26,375 included antipsychotic initiators with matched non-initiator controls between the ages of 6-17. Conditional logistic regression was used to examine the odds of being an antipsychotic user among those with past-year psychiatric diagnoses that have been previously found to be associated with antipsychotic use. RESULTS/ANTICIPATED RESULTS: Disorders with psychotic features were associated with the greatest differences in odds of antipsychotic prescription receipt. Specifically, children with bipolar or manic disorders had 145-fold greater odds of antipsychotic receipt than did those without bipolar or manic disorders (OR = 145.45, 95% CI = [95.64, 221.22]), whereas those with schizophrenia had 106-fold greater odds (OR = 105.89, CI = [67.40, 166.37]). However, these disorders occurred in only 12% and 8%, respectively, of the antipsychotic recipients. The most common disorders among those with antipsychotic receipt were depressive disorders and ADHD, which occurred in 46% and 43% of the recipients, respectively. Additionally, conduct disorder was present in 20% of recipients. DISCUSSION/SIGNIFICANCE: As expected, bipolar disorder and schizophrenia were strongly associated with initiation of pediatric antipsychotic treatment. Yet, most initiators did not have a diagnosis for either psychotic disorder or any other FDA-approved indications. This study highlights the critical need for further research on antipsychotic use among youth.

OBJECTIVES/SPECIFIC AIMS: High on-treatment platelet reactivity (HTPR) with clopidogrel imparts an increased risk for ischemic events in adults with coronary artery disease. Although more potent antiplatelet agents are available, clopidogrel remains the most commonly used P2Y12 inhibitor in Puerto Rico. Platelet reactivity varies with ethnicity and is influenced by both clinical and genetic variables; however, no clopidogrel pharmacogenetic studies with Puerto Rican patients have been reported. Therefore, we sought to identify clinical and genetic determinants of on-treatment platelet reactivity in a cohort of Puerto Rican patients with cardiovascular disease. METHODS/STUDY POPULATION: We performed a retrospective study of 111 Puerto Rican patients on 75 mg/day maintenance dose of clopidogrel. Patients were allocated into 2 groups: Group I, without HTPR; and Group II, with HTPR. Clinical data was obtained from the medical record. Platelet function was measured ex vivo using the VerifyNow® P2Y12 assay and HTPR was defined as P2Y12 reaction units (PRU)≥230. Genotyping of CYP2C19, ABCB1, PON1, PY2R12, B4GALT2, CES1, and PEAR1 was performed using Taqman® Genotyping Assays. RESULTS/ANTICIPATED RESULTS: The mean PRU across the cohort was 203±61 PRU (range, 8–324), and 42 (38%) patients had HTPR. One in four individuals carried at least 1 copy of the CYP2C19*2 variant allele. Hematocrit and PON1 p.Q192R variant were inversely correlated with platelet reactivity (p<0.05). Multiple logistic regression showed that 27% of the total variation in PRU was explained by a history of diabetes mellitus, hematocrit, CYP2C19*2, and PON1 p.Q192R. Body mass index (OR=1.15; CI: 1.03–1.27), diabetes mellitus (OR=3.46; CI: 1.05–11.43), hematocrit (OR=0.75; CI: 0.65–0.87), and CYP2C19*2 (OR=4.44; CI: 1.21–16.20) were the only independent predictors of HTPR. DISCUSSION/SIGNIFICANCE OF IMPACT: In a representative sample of Puerto Rican patients with cardiovascular disease, diabetes mellitus, hematocrit, CYP2C19*2, and PON1 p.Q192R were associated with on-treatment platelet reactivity. These factors may identify a subset of patients at higher risk for adverse events on clopidogrel in the Hispanic population.