OBJECTIVES/GOALS: To determine whether length of stay (LOS) and opioid prescribing differ among patients who present to the emergency department (ED) with low back pain (LBP) and serious mental illness (SMI+) compared to patients without SMI (SMI−). METHODS/STUDY POPULATION: Eligible patients that visited the ED within the Mount Sinai Health Care System from 2016-2019 were identified from the Mount Sinai Data Warehouse. Data on patient demographics, number of medications prescribed, and length of stay (LOS) were compared between the groups. Patients were excluded if English was not their primary language and if the LOS exceeded 24 hours. The final dataset consisted of 940 patients (SMI+: n = 181; SMI−: n = 759). RESULTS/ANTICIPATED RESULTS: SMI+ cases included patients with a diagnosis of depression (n = 152), anxiety (n = 134), schizophrenia (n = 9), bipolar (n = 1), and/or post-traumatic stress disorder (n = 33); 26% of cases had a single diagnosis, 66% with two, and the remaining 8% had three diagnoses. There was no significant difference in pain scores between the two groups (SMI-: 7.0 ± 0.1; SMI+: 6.8 ± 0.3; p = 0.6). We found no significant differences in LOS between the groups (SMI-: 3.9 ± 0.1 hours; SMI+: 3.8 ± 0.2 hours; p = 0.8), nor was there a significant difference in number of medications prescribed (SMI-: 1.7 ± 0.9; SMI+: 1.7 ± 0.6; p = 0.4). Further analysis revealed that the odds of receiving an opiate prescription in the SMI- group was 0.92 (95% CI: 0.54,1.55). DISCUSSION/SIGNIFICANCE OF IMPACT: Comparable opioid prescribing and LOS exist in patients with and without serious mental illness who are seeking treatment for low back pain in the ED. Despite similarities in approaches to care, more information is needed to determine if other social determinants influence these practices.

OBJECTIVES/GOALS: Vanishing White Matter Disease (VWM), is a childhood neurodegenerative leukodystrophy that presents with motor deficits, neurologic decline, and seizures leading to death.There are no treatments. Herein we investigate adeno-associated virus serotype 9 (AAV9) gene addition therapy for VWM. METHODS/STUDY POPULATION: To serve as a baseline for disease correction, we characterized the severe VWM Eif2b5I98M murine model with clinically relevant readouts including motor function, gait mapping and myelin loss through magnetic resonance imaging (MRI). Molecular characterization through the identification of biomarkers was also investigated. To provide targeted disease correction, we designed four gene replacement constructs to drive the rapeutic EIF2B5 expression in astrocytes—a critical cell type for VWM pathology. We are currently evaluating our AAV vectors in two murine VWM models, Eif2b5R191H and Eif2b5I98M, and are monitoring disease progression using traditional and clinically relevant readouts. RESULTS/ANTICIPATED RESULTS: The I98M mice display significant mobility loss, ataxic gait, and demyelination. Molecular characterization also indicates that the integrated stress response is significantly dysregulated, supporting the classic VWM phenotype. Our previous biodistribution study confirmed our ability to efficiently target astrocytes using varying iterations—including one novel—of the glial fibrillary acidic protein (GFAP) promoter. Our data suggests that targeting astrocytes with gene addition delays disease onset, partially rescues motor function, and attenuates myelin loss. Survival of the AAV9-gfaABC(1)D-EIF2B5 treated I98M mice is also significantly increased (p<0.0001), currently with a 2-fold extension in life expectancy. DISCUSSION/SIGNIFICANCE: Overall, we anticipate emergence of a lead astrocyte-targeted gene therapy candidate in which the data will be strengthened through the evaluation of clinically relevant measures in two murine models of disease, allowing fortimely translation to the clinic.

ABSTRACT IMPACT: Building a patient cohort to support clinical-translational research in chronic hepatitis B OBJECTIVES/GOALS: The overall objective of my KL2 project is to delineate the effect of HIV coinfection, and CHB disease stage and hepatitis B (HBV) viremia on the ability of toll-like receptor 8 agonism to restore HBV-specific immune cell function. This abstract describes the characteristics of the cohort from which research blood samples for my KL2 are collected. METHODS/STUDY POPULATION: HOPE is a prospective cohort study enrolling people with CHB including HIV/CHB coinfection, and resolved CHB. Participants are enrolled at primary care clinics in Maryland, Washington D.C., and Virginia. Standard-of-care antiviral treatment with tenofovir alafenamide (TAF) is prescribed through the study if indicated. Patients receiving TAF from the study are either starting treatment, or switching to TAF from another antiviral medication. If receiving TAF, participants are seen every 3-6 months for medication refills, clinical and research blood draws, and adverse event evaluations. Liver fibrosis is measured by FibroScan and a minority undergo liver biopsy. RESULTS/ANTICIPATED RESULTS: So far, 204 people have been enrolled, 177 with CHB (23 HIV/CHB coinfection), and 22 with resolved HBV infection. To date, 45 patients who were viremic at baseline and initiated on TAF have been enrolled. CHB predominantly affects Asian and African immigrants in the U.S, and the majority (77%) of HOPE participants are immigrants from these countries. The majority are male (70%), mean age 51 years (SD ±14). So far, 86 people with CHB monoinfection have been prescribed TAF on-study. Thirty-five percent of these had significant (>F2) liver fibrosis at baseline and half had elevated ALT (mean 47.5, SD ±55 IU/ml). Forty-three percent switched to TAF from another oral antiviral. Most switched due to lack of coverage by health insurance. DISCUSSION/SIGNIFICANCE OF FINDINGS: HOPE is a CHB cohort dedicated to collecting research samples and providing antiviral treatment. It is the foundation for the CHB translational research program at the University of Maryland School of Medicine. The availability of paired viremic and virally suppressed, HIV/CHB, and resolved HBV research samples are strengths of HOPE.

OBJECTIVES/GOALS: The purpose of the project was to create a Tableau dashboard to track metrics on requests for research data at Atrium Health Wake Forest Baptist. The objectives included: 1) define and identify request fulfillment metrics, 2) build a dashboard to capture metrics, and 3) integrate the dashboard into metrics tracking and reporting activities. METHODS/STUDY POPULATION: Project managers and team leaders in the Office of Informatics collaborated to determine which measures would be most relevant and impactful to report on. Metrics that were collected included: total count of tickets fulfilled over time, number of tickets currently open, sum of outstanding quoted hours, quoted hours vs. actual hours needed to fulfill ticket, and hours billed. Tableau's direct connection feature was used to extract the Trac ticket data from its Postgres database and the dashboard was published to Tableau Server. After the initial draft was created, several rounds of revisions were made as new data insights were discovered through further investigation of the data. RESULTS/ANTICIPATED RESULTS: Each morning, Tableau Server runs an automatic refresh of the data. On the dashboard homepage, users can see a quick view of all available metrics; to minimize noise, only the current statuses, active tickets, and stats for the most recent monitoring periods are displayed. Many of the charts give the user the option to link out to a page with related supplemental information (historic data, ticket status history, etc.). With the help of the dashboard, project managers and team leaders can now monitor how long tickets are in each status, increase quote accuracy using the hours quoted and hours billed charts, and examine ticket complexity over time. DISCUSSION/SIGNIFICANCE: Prior to dashboard creation, metrics were sparse and difficult to assemble. By providing information on the quantity, size, and complexity of data requests, the dashboard enables the Office of Informatics to monitor how the process is functioning overall, make informed decisions about resource allocation, and provide quick interventions.

OBJECTIVES/GOALS: Antibiotic treatment sets the stage for intestinal domination by Candida albicanswhich is necessary for development of invasive disease, but the resources driving this bloom remain poorly defined. We sought to determine these factors in order to design novel prophylaxis strategies for reducing gastrointestinal (GI) colonization. METHODS/STUDY POPULATION: We initially developed a generalizable framework, termed metabolic footprinting to determine the metabolites C. albicanspreferentially uses in the mouse GI tract. After identifying the metabolites C. albicansutilizes, we usedin vitro growth assays in the presence and absence of oxygen to validate out metabolomics findings. We next determined if a probiotic E. coli that utilizes oxygen would reduce C. albicanscolonization compared to a mutant E. coli that could not respire oxygen. Finding that oxygen was a necessary resource, we utilized germ-free mice to determine if Clostridiaspp. known to reduce GI oxygen would prevent C. albicanscolonization. Lastly, we sought to see if 5-aminosalicylic acid (5-ASA) could prevent C. albicanscolonization. RESULTS/ANTICIPATED RESULTS: We found that C. albicans preferentially utilizes simple carbohydrates including fructo-oligosaccharides (e.g., 1-kestose), disaccharides (e.g., β-gentiobiose), and alcoholic sugars (e.g., sorbitol) and is able to grow in vitro on minimal media supplemented with either of these nutrients. However, in the hypoxic environment that is found in the “healthy” colon, C. albicans cannot utilize these nutrients. We next found that pre-colonization in a mouse model with a probiotic E. coli significantly reduced C. albicanscolonization, but the mutant E. coli had no effect on colonization. We next showed that Clostridia supplementation restored GI hypoxia and reduced C. albicanscolonization. Remarkably, we found that 5-ASA significantly reduced GI colonization of C. albicans. DISCUSSION/SIGNIFICANCE: We have shown that C. albicans requires oxygen to colonize the GI tract. Importantly, we found that 5-ASA can prevent an antibiotic mediated bloom of C. albicans by restoring GI hypoxia, which warrants additional studies to determine if 5-ASA can be used as an adjunctive prophylactic treatment in high risk patients.

Objectives/Goals: NIH requires researchers submit Data Management and Sharing (DMS) Plans with their grant applications. Librarians developed an assessment tool for the plans and completed a pilot assessment in order to leverage the plans and understand current institutional research data management and sharing. Methods/Study Population: The assessment tool includes questions related to evaluations of DMS Plans as well as questions related to the content of the plans. Evaluation questions were adapted from the Federation of American Societies for Experimental Biology evaluation rubric developed for the DataWorks! Data Management Plan (DMP) Challenge. Fields were added to collect information on the content of DMS Plans, including data type, institutional resources, data repositories, data standards, and data dissemination timelines. The assessment tool was tested in a pilot implementation. Seven library workers were trained and completed paired review samples of 27 DMS Plans (54 evaluations total) in order to test for tool reliability. Results/Anticipated Results: Results include findings on the reliability of the tool as well as preliminary results from an assessment of DMS Plans. Findings on the reliability of the tool include assessments of the paired reviewers for each question included in the tool. Paired reviewers generally agreed, but tended to differ on specific questions, including questions pertaining to the data types generated or used in a research project. Questions with high levels of agreement included subjects of study and code sharing practices. Results on the content of the DMS Plans include information such as data repositories used, data oversight responsibilities, and data and metadata standards employed. Discussion/Significance of Impact: DMS Plans present an opportunity to better understand data management and sharing practices, and good data management supports high-quality, reproducible research. Developing and testing assessment tools for these plans is a key step toward understanding and improving current research data management practices.

OBJECTIVES/SPECIFIC AIMS: The purpose of the study was to describe patient characteristics associated with subsequent development of bowel ischemia. Primary outcomes were survival to discharge, 30-day and 1-year survival in patients with LVAD who subsequently develop bowel ischemia. Secondary outcomes included characteristics of patients who survive to discharge after bowel ischemia and those who do not. These included markers of patient condition prior to surgical/endoscopic intervention such as lactate levels, ICU admission, ventilator dependence, vasopressor and renal replacement requirements, as well as presence of sepsis. Of these, we predicted that lactate levels and white blood cell count would be significantly elevated pre- and post-operatively in patients who do not recover from bowel ischemic event. We used Mann-Whitney U Test to examine lactate levels between the two groups as our sample size was <30 and therefore necessitated the use of non-parametric testing. METHODS/STUDY POPULATION: In this single-center retrospective study, we analyzed all patients who underwent durable, CF-LVAD implantation at Duke University Medical Center (DUMC) between January 2008 and November 2018. Patients were screened using CPT codes for abdominal surgical exploration or ICD codes for intestinal vascular insufficiency. Final cohort was selected with confirmed diagnosis of intestinal ischemia based on surgical exploration or endoscopic intervention. Patient characteristics including pre-LVAD comorbidities, indication for LVAD implant, and clinical picture prior to bowel ischemic event were collected. Specific characteristics related to bowel ischemia were summarized, including diagnostic imaging, time from imaging study to operative intervention, and intraoperative details. Patient outcomes including survival to discharge, 30-day-, and 1-year survival were summarized. Patients were stratified based on survival to discharge status. Continuous variables were reported as median and interquartile range and compared using Mann-Whitney U test. Categorical variables were reported as proportions and compared using Fisher’s exact test as appropriate. RESULTS/ANTICIPATED RESULTS: A total of 754 patients underwent durable, CF-LVAD implant at DUMC, of which 21 subsequently developed intestinal ischemia (incidence 2.8%). The majority were male (81%) and treated as destination therapy (76.2%). Ten patients (50%) survived to discharge (one remains hospitalized). The proportions of patients receiving HeartMate II (60% vs. 50%, p=1.0), HeartMate III (20% vs. 10%, p=1.0), and HeartWare (20% vs. 40%, p=0.6) were not significantly different between patients who survived to discharge and patients who did not. Median time from LVAD implant to diagnosis of bowel ischemia did not vary significantly between the patient groups (11.5 days, IQR 34.75 vs. 16.5 days, IQR 173.8; p=0.40), nor did the median time from diagnosis to surgical intervention (264.5 minutes, IQR 497.8 vs. 323 minutes, IQR 440, p=0.82). In the 48 hours leading to diagnosis and intervention, renal replacement therapy (50% vs. 0%, p=0.033) was more prevalent in patients who did not survive to discharge. Differences in pre- and post-operative lactate levels were not significantly different in patient groups. A similar pattern of diagnostic study preference emerged from both groups, with CT being the most common (76.2%) followed by KUB (42.9%). Upper endoscopy/colonoscopy was performed in 7 patients (33.3%), of which 5 also had operative exploration. A total of 19 patients underwent abdominal exploration (90.5%). Nine had large bowel resection (42.9%) while 14 had small bowel resection (66.7% with average 75cm removed). Overall survival at 1-year was 33%. For those making it to discharge (n=10), one year survival was 60%. DISCUSSION/SIGNIFICANCE OF IMPACT: This is the first institutional study to our knowledge to describe intestinal ischemia in patients receiving CF-LVAD therapy. Intestinal ischemia in patients receiving CF-LVAD therapy is associated with high mortality and morbidity. Diagnosis of bowel ischemia should be considered in patients presenting with clinical symptoms of bowel ischemia in addition to requirement of renal replacement therapy. Imaging modalities used were dependent on the clinical situation and were not always necessary prior to intervention. Further investigation is warranted to identify predictors of this morbid complication.

This study proposes a new practical approach for tracking institutional changes in research teamwork and productivity using commonly available institutional electronic databases such as eCV and grant management systems. We tested several definitions of interdisciplinary collaborations based on number of collaborations and their fields of discipline. We demonstrated that the extent of interdisciplinary collaboration varies significantly by academic unit, faculty appointment and seniority. Interdisciplinary grants constitute 24% of all grants but the trend has significantly increased over the last five years. Departments with more interdisciplinary grants receive more research funding. More research is needed to improve efficiency of interdisciplinary collaborations.

The commercialization of medical devices and biotechnology products is characterized by high failure rates and long development lead times particularly among start-up enterprises. To increase the success rate of these high-risk ventures, the University of Massachusetts Lowell (UML) and University of Massachusetts Medical School (UMMS) partnered to create key academic support centers with programs to accelerate entrepreneurship and innovation in this industry. In 2008, UML and UMMS founded the Massachusetts Medical Device Development Center (M2D2), which is a business and technology incubator that provides business planning, product prototyping, laboratory services, access to clinical testing, and ecosystem networking to medical device and biotech start-up firms. M2D2 has three physical locations that encompass approximately 40,000 square feet. Recently, M2D2 leveraged these resources to expand into new areas such as health security, point of care technologies for heart, lung, blood, and sleep disorders, and rapid diagnostics to detect SARS-CoV-2. Since its inception, M2D2 has vetted approximately 260 medical device and biotech start-up companies for inclusion in its programs and provided active support to more than 80 firms. This manuscript describes how two UMass campuses leveraged institutional, state, and Federal resources to create a thriving entrepreneurial environment for medical device and biotech companies.

Intervention development frameworks offer the behavioral sciences a systematic and rigorous empirical process to guide the translation of basic science into practice in pursuit of desirable public health and clinical outcomes. The multiple frameworks that have emerged share a goal of optimization during intervention development and can increase the likelihood of arriving at an effective and disseminable intervention. Yet, the process of optimizing an intervention differs functionally and conceptually across frameworks, creating confusion and conflicting guidance on when and how to optimize. This paper seeks to facilitate the use of translational intervention development frameworks by providing a blueprint for selecting and using a framework by considering the process of optimization as conceptualized by each. First, we operationalize optimization and contextualize its role in intervention development. Next, we provide brief overviews of three translational intervention development frameworks (ORBIT, MRC, and MOST), identifying areas of overlap and divergence thereby aligning core concepts across the frameworks to improve translation. We offer considerations and concrete use cases for investigators seeking to identify and use a framework in their intervention development research. We push forward an agenda of a norm to use and specify frameworks in behavioral science to support a more rapid translational pipeline.

OBJECTIVES/GOALS: Our aims are to 1) describe changes in thumb Carpometacarpal (CMC1) joint stability following an 8-week clinic-based dynamic stability exercise program using computerized tomography (CAT) and 2) to evaluate the agreement between ultrasound and CAT (reference standard) when quantifying thumb CMC stability. METHODS/STUDY POPULATION: Aim 1: We have enrolled 13/49 participants in a prospective pre-post interventional study of an 8-week clinic-based occupational therapy dynamic stability program. The primary outcome will be change in stability (thumb metacarpal subluxation in mm) when forcefully loading the thumb as per CAT from pre-treatment to post-treatment at 9 weeks. Aim 2: Same 49 participants are undergoing a one-time ultrasound during baseline assessment. Agreement of ultrasound and CAT measurements (thumb metacarpal subluxation in mm) will be assessed by the Bland-Altman method. RESULTS/ANTICIPATED RESULTS: Exercise is a first-line treatment of CMC1 OA yet there is insufficient evidence to support this. Progression of CMC1 OA is characterized by altered joint mechanics. Joint replacement surgery may reduce pain but often worsens thumb mechanics and overall hand function. This study is the first to test the sustained biomechanical effects of non-invasive thumb exercises. Should these benefits exist, this will further support exercise as a first-tier intervention. Should ultrasound be a suitable proxy for CAT, therapists/physicians could monitor thumb CMC mechanics in response to treatment without risk of radiation exposure. We anticipate 1) a statistically significant reduction in thumb CMC subluxation at 9 weeks follow up and 2) high agreement between sonographic and CAT measures of thumb stability. DISCUSSION/SIGNIFICANCE: This study will lay the foundation for future work and may offer critical support for the use of a non-pharmacological and non-surgical approach as first-line treatment of a highly disabling disease. Future study should include controlled trials where hand function, activity limitation, disease progression, and costs are the outcomes in interest.

Objectives/Goals: Although several studies have identified significant associations between specific social determinants of health (SDoH) and adverse outcomes, little is known about how SDoH co-occur to form subtypes and their outcome-based risks. Here we analyze how SDoH co-occur across all participants with a cancer diagnosis in the All of Us program. Methods/Study Population: Data: All participants (n = 3361) with cancer and their responses to 110 survey questions related to SDoH. Independent variables: 18 SDoH factors aggregated from the questions to address uneven granularity. Dependent variables: depression, delayed medical care, and ER visits in the last year. Analytical Method. (1) Bipartite network analysis with modularity maximization to identify participant-SDoH biclusters, measure the degree of their biclusteredness (Q), and estimate the significance of Q. (2) Visualization of the results using the ExplodeLayout force-directed algorithm. (3) Multivariable logistic regression (adjusted for demographics and corrected through FDR) to measure the odds ratio (OR) of each bicluster compared pairwise with the other biclusters to estimate their risk for the 3 outcomes. Results/Anticipated Results: As shown in Fig. 1A (http://www.skbhavnani.com/DIVA/Images/Cancer-SDoH.jpg), the analysis (n = 3361, d = 18) identified 4 biclusters with significant biclusteredness (Q = 0.13, random-Q = 0.11, z = 9.94, P Discussion/Significance of Impact: Currently, many health equity policies allocate resources based on sociodemographic factors like race and income to address disparities. The 4 distinct subtypes and their outcome-based risks suggest that such policies could be more precise if they were based directly on combinations of need using SDoH subtypes and their risk stratification.

OBJECTIVES/GOALS: CTSA Program hubs provide a wide range of research support services (funding, training, consultations, etc.) to individuals and teams. The CTSA Program hub at Columbia University seeks to identify best practices across CTSA hubs in how they facilitate researchers to identify, navigate, and access services at complex academic medical centers. METHODS/STUDY POPULATION: o A landscape analysis across CTSA Program hub websites was conducted during December 2021-February 2022, with the goal of assessing the availability of research navigation services and the ease of accessing and requesting research support services at each hub. Websites of 66 CTSA hubs were accessed and browsed for the following: 1) if a research navigation or concierge service was available; 2) how to request and apply to use common services such as pilot funding, biostatistics, clinical research services; 3) if there was a contact form and/or email address for general inquiries. Binary coding (1=Yes, 2=No) was used to track and summarize if these features were available, and then further classification and observations were noted into the full data set. RESULTS/ANTICIPATED RESULTS: The landscape analysis determined that 68% of CTSA hubs offer a form of research navigation including consultative models (personalized guidance, studios) and web-based models (self-service web portals, graphics, toolkits). Consultative models could be classified into three levels of support ranging from general information sharing to providing scientific expertise to convening more intensive studio sessions. 92% of CTSA hubs have at least 1 system in place for researchers to request services with a majority of hubs using a mix of tools and systems. In addition, 36% of hubs have additional general contact forms and 75% have general email addresses to assist researchers in obtaining more information. DISCUSSION/SIGNIFICANCE: There is a relative lack of data and information on the effectiveness of different research navigation models across the CTSA network, and barriers for researchers to identify services remain (Elworth et al). Our team is planning additional evaluations including interviews with leaders at other CTSA hubs and researchers and trainees at Columbia.

OBJECTIVES/GOALS: Morehouse School of Medicine (MSM), TxTM is a scientific philosophy promoting interdisciplinary approaches towards exponential advances in community and population health. Objectives are to detail the model, pilot funding mechanism, early research findings and infrastructure investments. METHODS/STUDY POPULATION: The health research system has widely acknowledged challenges that can delay research translation to systems that advance health for chronically disadvantaged health disparity population groups. MSM’s vision is to lead the creation and advancement of health equity. The vision-aligned strategic plan prioritized formalization of a TX TM implementation priority. The study population was the institution’s research faculty and leaders, research administration, and communication arm. Through a cross-institutional working group, a plan was deployed to 1) assess the institutional landscape, 2) review the grey and peer reviewed literature on translational research and 3) invest in a pilot research funding mechanism. RESULTS/ANTICIPATED RESULTS: Over $700K has been invested in TX TM implementation. Over half of research faculty completed an institutional landscape assessment to identify translational research expertise, interests and points of interest in new collaboration. The most frequently cited collaborative research interests were clinical research with human subjects, patient-centered outcomes and laboratory-based research with human subjects/specimens. Funded multidisciplinary and/or community-engaged pilot studies investigate the role for circadian rhythms and shift work, cultural variables influencing mental health among Haitians living in the US and integrating prescription reconciliation telehealth in primary care. DISCUSSION/SIGNIFICANCE OF IMPACT: TX TM requires interdisciplinary collaboration across translational research spheres and beyond the academy. Institutional investment, infrastructure support and senior-level champions are central to awareness and rewarding such scholarship towards scaling approaches that advance health equity. CONFLICT OF INTEREST DESCRIPTION: Coined at Morehouse School of Medicine (MSM), Tx TM symbolizes an approach and scientific philosophy designed to intentionally promote and support convergence of interdisciplinary approaches and scientists to stimulate exponential advances for the health of diverse communities.

Objectives/Goals: Dravet syndrome is a developmental and epileptic encephalopathy associated with refractory seizures and a high risk of sudden unexpected death in epilepsy. A pathogenic biallelic variant in SCN1B, SCN1B-p.R98C, was identified in three patients with Dravet syndrome. Here we investigate SCN1B-p.R98C on neuronal function in vivo. Methods/Study Population: Scn1b-p.R98C mice were previously generated using CRISPR-Cas9 gene editing. Homozygous animals exhibit increased susceptibility to hyperthermia induced seizures at postnatal day (P) 15, 100% expression of spontaneous generalized seizures by P30, and ~20% undergo SUDEP by approximately P60. Here we examined the neuronal phenotype of P17–28 male and female Scn1b-p.R89C mice. We used whole-cell patch clamp electrophysiology approaches to measure effects of the variant on passive membrane properties, intrinsic excitability, and single action potential properties of parvalbumin positive (PV+) interneurons and pyramidal neurons in layers 5/6 of the somatosensory cortex and CA1 region of the hippocampus. Wild-type littermates were used as controls. Results/Anticipated Results: Our results show no differences between genotypes in any measure for somatosensory cortical PV+ interneurons or pyramidal neurons. In the CA1 region of the hippocampus, we found no differences for any measure in PV+ interneurons. In contrast, CA1 pyramidal neurons were hyperexcitable, however, with no changes in passive membrane properties or single action potential properties. Discussion/Significance of Impact:

OBJECTIVES/GOALS: The goal of the CTSA consortium is to move scientific discoveries to clinical application. Translational science (TS) focuses on the process by which this happens, and NCATS supports pilot projects that propose TS questions. We are developing a rubric to guide program managers’ability to discriminate between TS and translational research (TR). METHODS/STUDY POPULATION: The CTSA External Review Exchange Consortium (CEREC) and CEREC II are reciprocal review collaborations between CTSA hubs that identify reviewers for each other’s pilot grant applications. CEREC and CEREC II partners developed a 31-item rubric, based on NIH’s Translational Science Principles, for discriminating pilot TS grant applications from those proposing TR. The hubs contributed proposals pre-selected as either TS or TR projects. Then, experienced reviewers and/or program administrators from the hubs used the rubric to score each of the proposals. Reliability of the rubric will be assessed using inter-rater reliability (% agreement and kappa). To identify which of the items in the rubric best discriminate between TS and TR, Item Response Theory analysis will be employed. RESULTS/ANTICIPATED RESULTS: Ten CEREC participating hubs submitted 30 applications: 20 TS proposals and 10 TR proposals. Twenty-two reviewers from 12 CEREC hubs evaluated the applications by using the scoring rubric; at least two reviewers evaluated each proposal. The results of the analyses will describe the reliability of the rubric and identify which of the seven TS Principles are most useful for distinguishing between TS and TR pilot grant proposals. Ultimately, this work will yield a scoring rubric that will be disseminated throughout the CTSA network to facilitate the screening of TS applications. DISCUSSION/SIGNIFICANCE: Optimizing research processes is critical to ensure that scientific discoveries are integrated into clinical practice and public health policy as rapidly, efficiently, and equitably as possible. By appropriately identifying and funding TS projects, CTSA hubs can accelerate the impact of clinical and translational research.

OBJECTIVES/GOALS: We seek to develop a 3D perfusion culture imaging plate for human fecal bacteria co-culture with epithelial cells in a structure that mimics the gut epithelium. We will develop this system for use with patient fecal samples to characterize patient risk of developing cancer. METHODS/STUDY POPULATION: E. coli NC101, a strain that harbors the pks gene island, produces the genotoxin colibactin which causes DNA damage that can lead to colorectal cancer development. The genotoxic ability of this bacterium is dependent upon cell-to-cell contact. Here, we present 3D printed E. coli NC101 and intestinal epithelial cells (IEC-6) in a perfusion imaging plate, enabling visualization of the cytotoxic effects of the bacteria in real time using confocal microscopy, in combination with flow cytometry analysis for cell cycle arrest (a surrogate marker of DNA damage). RESULTS/ANTICIPATED RESULTS: 40,000 IEC-6 cells were 3D printed in a cylindrical layer in our triple well imaging plate. The cells were infected at an MOI of 100 for 18 hours and time lapse images of the infection were recorded by confocal microscopy. The cells were then harvested for analysis by flow cytometry for cell cycle arrest as a measure of DNA damage. Our images and flow cytometry data show that E. coli NC101 co-localizes with IEC-6 cells and causes cell cycle arrest in phase G2 (infected %G2 = 40.1), compared to uninfected cells (%G2 = 24.7, P = 0.034). Mutant strains lacking adhesion protein FimH or the ability to produce colibactin do not cause G2 cell cycle arrest (P = 0.844 and P = 0.644, respectively). DISCUSSION/SIGNIFICANCE OF IMPACT: We are able to recapitulate the DNA damage phenotype of E. coli NC101 in our 3D culture system. We show here that host-microbe interactions leading to cancer can be modeled in our 3D perfusion system, and we will next use patient fecal samples in our culture system.

ABSTRACT IMPACT: Because diabetes disproportionately affects residents in the Deep South, identifying factors increasing the risk of hospital readmissions unique to this population can translate to tailored interventions and strategies to improve transitions of care and patients’ health outcomes. OBJECTIVES/GOALS: Patients with diabetes (PWD) are susceptible to hospital readmissions due to inadequate transitions of care (TOC). To better understand how to improve TOC, the objective of the study is to identify factors associated with readmissions among PWD in Alabama disproportionally affected by diabetes. METHODS/STUDY POPULATION: This retrospective cohort study utilizes electronic health record data from an urban health system in Alabama. The study population includes adults (≥18 years old) diagnosed with diabetes who were hospitalized between 2016 and 2020. Women who are pregnant during hospitalization or diagnosed with gestational diabetes are excluded. Patient’s index hospitalization is identified with a 3-month washout period preceding admission. The primary outcome is all-cause 30-day readmission. Characteristics are compared between patients with and without readmissions. Factors significantly associated with readmissions are identified with multiple logistic regression, adjusted for potential confounders. RESULTS/ANTICIPATED RESULTS: The sample size is expected to be around 30,000 individual PWD. Anticipated results include estimation of the all-cause 30-day readmission rate experienced by the PWD in Alabama. It is expected that various factors will be associated with either higher or lower odds of readmission, interpreted via odds ratios and 95% confidence intervals. Factors investigated are driven by previously identified risk factors of readmission from the literature, including but not limited to sociodemographic variables, lab values (A1C, glucose, serum albumin, serum sodium, etc.), vital signs (blood pressure), comorbidities, medications, length of stay, insurance coverage, geographic location, and social history. DISCUSSION/SIGNIFICANCE OF FINDINGS: Findings will establish evidence-based knowledge about TOC for PWD in the Deep South, specifically Alabama. Identifying factors associated with readmissions among PWD in Alabama will inform TOC intervention studies tailored to populations in the Deep South to effectively mitigate readmissions.