OBJECTIVES/GOALS: The objective of this study is to examine the relationship between gastro-intestinal (GI) patients’ health literacy levels and patients’ health outcomes (length of stay, readmission, complication). METHODS/STUDY POPULATION: A research team at the University of Alabama at Birmingham (UAB) ‘s Gastro-Intestinal (GI) surgical department collected inpatient GI patients’ health literacy data by distributing the Brief Health Literacy Screen (BRIEF) survey to patients are about to be discharged. Patients’ health outcomes data were gathered through Business Objects, an online platform that allows physicians and researchers to access and gather patients’ medical information with an IRB approval. After accounting for necessary control variables, logistic regression and multiple linear regression models will be run to assess whether there is a significant relationship between patients’ health literacy levels and patients’ health outcomes. RESULTS/ANTICIPATED RESULTS: Three specific hypotheses are proposed in this study. H1: GI patients’ health literacy levels will be negatively associated with their lengths of stay H2: GI patients’ health literacy levels will be negatively associated with their readmission status to the hospital H3: GI patients’ health literacy levels will be negatively associated with their complication status to the hospital DISCUSSION/SIGNIFICANCE OF IMPACT: This study allows us to further our understanding of patients’ health literacy level and its’ relationship with important health outcomes. By looking at a variety of diverse health outcomes, the impact of a patients’ health literacy level on that patients’ health outcomes will be observed more clearly.

ABSTRACT IMPACT: Improved understanding of the relationship between level of response to alcohol and body weight in the context of other contributing factors will help inform prevention and intervention efforts regarding obesity. OBJECTIVES/GOALS: We evaluated the association between level of response to alcohol and weight status across the spectrum of alcohol misuse. We hypothesized that lower level of response to alcohol would be associated with heavier weight, after controlling for obesity risk factors like food addiction, impulsivity, and low socioeconomic status. METHODS/STUDY POPULATION: Adult participants (N=587) enrolled in NIAAA’s natural history study completed Self-Rating of the Effects of Alcohol (SRE), a retrospective measure of level of response to alcohol, along with Lifetime Drinking History (LDH); Yale Food Addiction (FA) Scale; Barratt Impulsiveness Scale (BIS); Delayed Discounting Task (DDT). Structured Clinical Interviews for DSM disorders were conducted to identify individuals with current alcohol use disorder (AUD). Body mass index (BMI), computed from height and weight measured during the study, and used to stratify participants into 3 groups: normal weight (N=222), overweight (N=219), or obese (N=146). RESULTS/ANTICIPATED RESULTS: SRE scores during heaviest drinking period were lowest in the heavier weight group, after accounting for FA, impulsivity, alcohol-related, and demographic variables (ê•2=238.5, p=0.002, Cox and Snell Pseudo R2=0.43). Compared to the obese group, normal weight and overweight groups had fewer FA symptoms and higher BIS cognitive complexity (p values<0.01) but similar rates of current AUD. Relative to the obese group, the normal weight group was more likely to be White, and to have lower household incomes but more education, more years of heavy drinking (LDH), and steeper delayed discounting, p values ≤0.03. The overweight group had a higher proportion of males than did the obese group, p<0.001. DISCUSSION/SIGNIFICANCE OF FINDINGS: Lower level of response during heaviest drinking period was significantly associated with current weight status, suggesting a relationship between alcohol sensitivity and BMI. Future work will explore pharmacokinetic-pharmacodynamic and additional risk factors underlying this relationship.

OBJECTIVES/GOALS: Annually, 1.5 million global patients receive maxillofacial reconstruction. The gold standard, involving bone particulate, lacks reproducibility. To improve this, we have developed a custom 3D-printable, porous cover-core design. This study optimizes the hydrogel core properties and growth factor (GF) release for enhanced bone regeneration. METHODS/STUDY POPULATION: Different ratios of Methacrylated Gelatin (GelMa), Methacrylated Alginate (AlgMa) and tricalcium phosphate (α²-TCP) were combined to optimize cell viability, GF sequestration and mechanical stability. Material characterization was performed using a rheometer to determine the viscoelastic properties of the blends. Release from disks loaded with FGF-containing PLGA microparticles was quantified with an ELISA kit. Furthermore, scanning electron microscopy (SEM) was conducted to quantify hydrogel porosity. In vitro studies were performed using NIH 3T3 murine fibroblasts in Corning Transwells while immunofluorescent, metabolic and osteogenic studies were performed in 96 well plates to investigate cell infiltration, cell adhesion, viability and differentiation, respectively. RESULTS/ANTICIPATED RESULTS: By adjusting the AlgGelMa ratio, we manipulated matrix properties. GelMa possesses excellent durability and cell adhesion due to intrinsic RGD-binding motifs. AlgMa enhanced swelling by 30%, growth factor sequestration by 50% in 24hrs, and matrix storage modulus without increasing the loss modulus which could cause cell migration away from the hydrogel. Varying the AlgGelMa ratio lowered pH, promoted cell infiltration, and reduced fibronectin accumulation. The addition of β-TCP is anticipated to improve cell differentiation towards an osteogenic lineage due to improved elastic modulus, calcium and phosphate ion concentration improving mineral deposition. DISCUSSION/SIGNIFICANCE: These findings suggest through the use of this composite, early cell infiltration can be increased and promoted due to FGF release, leading to increased osteointegration. Our porous cover-core design ensures efficient clot integration and early cell infiltration, enhancing osteointegration through FGF release.

OBJECTIVES/GOALS: To investigate the relationship between abnormal bacterial colonization of the gastrointestinal (GI) tract and systemic abnormalities in innate immunity as it contributes to the pathogenesis of rosacea. METHODS/STUDY POPULATION: This is a prospective observational study of patients with erythematotelangiectatic or papulopustular rosacea. The study participants will undergo urea breath testing for Helicobacter pylori (Hp) and hydrogen-methane breath testing for small intestinal bacterial overgrowth (SIBO). Colonic microbiome analysis will be performed using 16S rRNA sequencing of fecal samples. Further, key pro-inflammatory cytokines will be quantified from serum samples. Markers for rosacea subjects and subgroups will be compared by standard analysis of variance methods where appropriate, and Tukey studentized range tests will be done for specific comparisons. Chi-square tests will be used to assess group differences in categorical data. At least 42 subjects will be studied to provide 80% power atα-0.05. RESULTS/ANTICIPATED RESULTS: We hypothesize that the results of this study will support an observed relationship between abnormal GI bacterial colonization and systemic innate immunity abnormalities in rosacea as determined by three primary endpoints: a significantly greater prevalence of Hp and SIBO in rosacea participants, presence of pro-inflammatory cytokines linked to rosacea pathogenesis including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, and Granulocyte-macrophage colony-stimulating factor (GM-CSF), and observation of distinct, metabolically active colonic bacterial communities specific to rosacea participants. DISCUSSION/SIGNIFICANCE: By identifying rosacea as a cutaneous manifestation of a more systemic inflammatory disease, the results of this study will have implications for the development of important pharmacological interventions targeting key inflammatory pathways in rosacea pathogenesis.

OBJECTIVES/GOALS: Lung cancer is the leading cause of cancer-related mortality in the United States for both men and women. African Americans are disproportionately affected with lung cancer, having higher incidence and mortality rates compared to Caucasian men and women. African American smokers are diagnosed with lung cancer at a lower age with lower cumulative smoking history. Differences in socioeconomic and environmental factors likely contribute to lung cancer disparities, but less is known about acquired biologic alterations that can promote initiation and progression of lung cancer, particularly in African Americans. This is of interest because there may be other biological, genetic, or environmental factors contributing to lung cancer outcomes as it relates to differences in gender and race. One potential biologic variable may be in the DNA repair capacity (DRC), which describes a cell’s ability to repair damage to DNA caused by carcinogens, oxidants, and radiation. Altered DNA repair is a hallmark of cancer, leading to mutations and malignant transformation. We hypothesize that DRC is decreased in African Americans with lung cancer compared to Caucasian Americans with lung cancer, contributing to the disparity that exists in this racial group. We will 1) perform a retrospective chart review to determine demographic differences between African Americans and Caucasians at three central Indiana hospitals and 2) determine the impact of race and lung cancer on DRC amongst African Americans and Caucasians with and without lung cancer. METHODS/STUDY POPULATION: Lung cancer patients are identified in 3 central Indiana hospitals with different payer source and patient populations using ICD codes. Collected demographics include age, gender, pack-years, lung cancer histology, treatment, and mortality. DRC is measured by host-cell reactivation (non-homologous end-joining and nucleotide excision repair pathways) by flow-cytometry. Measurement of DRC is performed on PBMCs obtained from 120 patients (male and female, African Americans and Caucasians with and without lung cancer). Correlation of DRC and lung cancer will be determined by comparing lung cancer diagnosis to quartile DRC, and adjusted for confounders (measured demographics). Correlative measures will include measures of DNA damage and genomic instability. RESULTS/ANTICIPATED RESULTS: 3450 lung cancer patients were diagnosed with lung cancer at Indiana University Hospital between 1/1/2000 – 5/31/2015. Of these, 48.2% were female and 92.7% smokers. African Americans, Caucasians and Other ethnicities represented 12%, 86% and 2%, respectively. Of smokers, 11.4% were African American. The primary payer source was Federal/Medicare. Retrospective review of lung cancer patients from two additional health systems (county and VA hospitals) will be performed as above with outcomes measured. DRC and additional correlative measures will be performed as in Methods. DISCUSSION/SIGNIFICANCE OF IMPACT: If present, altered DRC in African Americans compared to Caucasians may contribute to the disproportional impact of lung cancer on African Americans. If DRC is decreased in African Americans with lung cancer, future studies will focus on identifying potential genetic, epigenetic and environmental causes for this decrease.

OBJECTIVES/GOALS: To examine the individual and combined association between preoperative sleep disturbance (SD) and depression and 12-month disability, back pain, and leg pain after lumbar spine surgery (LSS). METHODS/STUDY POPULATION: We analyzed prospectively collected multi-center registry data from 700 patients undergoing LSS (mean age=60.9 years, 37% female, 89% white). Preoperative SD and depression were assessed with PROMIS measures. Established thresholds defined patients with moderate/severe symptoms. Disability (Oswestry Disability Index) and back and leg pain (Numeric Rating Scales) were assessed preoperatively and at 12 months. We conducted separate regressions to examine the influence of SD and depression on each outcome. Regressions examined each factor with and without accounting for the other and in combination as a 4-level variable. Covariates included age, sex, race, education, insurance, body mass index, smoking status, preoperative opioid use, fusion status, revision status, and preoperative outcome score. RESULTS/ANTICIPATED RESULTS: One hundred thirteen (17%) patients reported moderate/severe SD alone, 70 (10%) reported moderate/severe depression alone, and 57 (8%) reported both moderate/severe SD and depression. In independent models, preoperative SD and depression were significantly associated with 12-month outcomes (all p’s<0.05). After accounting for depression, preoperative SD was only associated with disability, while preoperative depression adjusting for SD remained associated with all outcomes (all p’s<0.05). Patients reporting both moderate/severe SD and moderate/severe depression had 12.6 points higher disability (95%CI=7.4 to 17.8) and 1.5 points higher back (95%CI=0.8 to 2.3) and leg pain (95%CI=0.7 to 2.3) compared to patients with no/mild SD and no/mild depression. DISCUSSION/SIGNIFICANCE: Preoperative SD and depression are independent predictors of 12-month disability and pain when considered in isolation. The combination of SD and depression impacts postoperative outcomes considerably. The high-risk group of patients with moderate/severe SD and depression could benefit from targeted treatment strategies.

OBJECTIVES/GOALS: To identify an electroencephalographic (EEG) signature of SOR in adults with TS METHODS/STUDY POPULATION: We will recruit 60 adults with CTD and 60 sex- and age-matched healthy controls to complete scales assessing severity of SOR (Sensory Gating Inventory, SGI), tics, and psychiatric symptoms. Subjects will then be monitored on dense-array scalp EEG during sequential auditory and tactile sensory gating paradigms, as such paradigms have been shown to correlate with self-report measures of SOR in other populations. Single-trial EEG data will be segmented into 100-ms epochs and spectrally deconvoluted into standard frequency bands (delta, theta, alpha, beta, gamma) for pre-defined regions of interest. We will conduct between-group contrasts (Wilcoxon rank-sum) of band-specific sensory gating indices and within-group correlations (Spearman rank correlations) between sensory gating indices and SGI scores. RESULTS/ANTICIPATED RESULTS: We hypothesize that, relative to controls, adults with CTD exhibit impaired sensory gating and that extent of impairment correlates with severity of SOR. 14 adults with CTD (9 men, 5 women) and 16 controls (10 men, 6 women) have completed the protocol to date. Within this sample, adults with CTD showed significantly reduced sensory gating compared to controls in frontal (CTD median 0.12 dB (interquartile range -0.15–0.70 dB); control -0.37 dB (-0.80–-0.13 dB); p = 0.01) and parietal (CTD 0.17 dB (-0.08–0.50 dB); control -0.20 dB (-0.43–0.10 dB); p = 0.01) gamma band during the 100-200 ms epoch in the tactile paradigm. No significant between-group differences were evident for the auditory paradigm. Among adults with CTD, multiple sensory gating indices significantly correlated with SGI scores. Enrollment continues. DISCUSSION/SIGNIFICANCE: Results aim to clarify the extent of sensory gating impairment in TS and identify a clinical correlate of neurophysiologic dysfunction in the disorder. Such knowledge has direct implications for identification of candidate neurophysiologic biomarkers, an express goal of the National Institutes of Health.

OBJECTIVES/SPECIFIC AIMS: The aim is to investigate if sustained weight loss due to caloric restriction can be achieved in a community setting, using faith-based organisations (FBOs) as hubs; and if this weight loss can lead to the re-establishment of normal metabolism (using the normalisation of blood sugar levels while off glucose lowering medication as a proxy) in a person with pre-diabetes or T2DM. METHODS/STUDY POPULATION: Members of the FBO with either a diagnosis of T2DM for <6 years or pre-diabetes as defined by the American Diabetes Association (ADA); and a Body Mass index (BMI) of ≥27 kg/m2 are eligible. After counselling, participants will be placed on a 12 week low calorie liquid diet, supplemented by low carbohydrate vegetables, totalling approximately 840 kcal/day. During this time, participants will be monitored weekly at their FBO by trained members of their congregation, with oversight from the study team, for change in weight, fasting blood glucose, waist and hip circumference and blood pressure. This will be followed by a 3 month period during which participants will receive ongoing dietary advice as they transfer to a balanced, reduced calorie, solid diet. Physical measurements will be monitored monthly during this 3 month period. The next 6 months is a period where the participants and the FBO health team move towards ‘independence’. This involves further training of the FBO health team and participants in healthy lifestyle habits; and a commitment by the leadership of the FBO to assume ‘ownership’ for NCD monitoring within their community. Physical measurements will be repeated at the end of one year. RESULTS/ANTICIPATED RESULTS: Based on previous studies, we expect that participants who are compliant to the diet will lose approximately 2.2 kg per week over the 12 week period. This will be associated with rapid (within 1 week) normalisation of fasting blood glucose levels (<7mmol / L). We expect that, due to the accessibility of NCD monitoring and support, that participants to be satisfied with their care and compliant to their regime and that the results of the first 12 weeks will be sustained at the 12 month follow up. We expect that the FBO leadership will assume the responsibility of continuing and NCD programme, not only for the local congregation but for the surrounding community. DISCUSSION/SIGNIFICANCE OF IMPACT: Diabetes remission with a low calorie diet is a viable intervention for T2DM remission however social support is key to an individual’s success. This novel study which proposes institution of a diabetes remission intervention which fits into the participant’s locale and involves peer support, should increase long-term success.

OBJECTIVES/GOALS: Strong evidence has implicated oxidative stress (OS) as a disease mechanism in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The study aim was to assess whether a C>T single nucleotide polymorphism (SNP) (rs1800668), which reduces the activity of glutathione peroxidase 1 (GPX1), is associated with brain OS in patients with ME/CFS. METHODS/STUDY POPULATION: Study population: The study enrolled 20 patients with ME/CFS diagnosed according to Canadian Consensus Criteria, and 11 healthy control (HC) subjects. Genotyping: DNA was extracted from whole blood samples, amplified by PCR, and purified. Sanger sequencing was used for genotyping. 1H MRS: Proton magnetic resonance spectroscopy (1H MRS) was used to measure levels of glutathione (GSH)— a primary tissue antioxidant and OS marker— in a 3x3x2 cm3 occipital cortex (OCC) voxel. GSH spectra were recorded in 15 minutes with the standard J-editing technique. The resulting GSH peak area was normalized to tissue water level in the voxel. Statistical Analysis: T-tests were used to compare OCC GSH levels between ME/CFS and HC groups, and between the study’s genotype groups (group 1: CC, group 2: combined TC and TT). RESULTS/ANTICIPATED RESULTS: Clinical characteristics: ME/CFS and HC groups were comparable on age and BMI but not on sex (p = 0.038). Genotype frequencies: Genotype frequencies in the ME/CFS group were 0.55 (CC), 0.25 (TC) and 0.2 (TT); and 0.636 (CC), 0.364 (TC), and 0 (TT) in the HC group. GSH levels: There was a trend-level lower mean OCC GSH in ME/CFS than in HC (0.0015 vs 0.0017; p = 0.076). GSH levels by genotype group interaction: Within the ME/CFS group but not in the combined ME/CFS and HC group or HC group alone, GSH levels were lower in the TC and TT genotypes than in CC genotypes (0.00143 vs 0.00164; p = 0.018). DISCUSSION/SIGNIFICANCE: This study found that the presence of a C>T SNP in GPX1 is associated with lower mean GSH levels and, hence, brain oxidative stress, in ME/CFS patients. If validated in a larger cohort, this finding may support targeted antioxidant therapy based on their genotype as a potentially effective treatment for patients with ME/CFS.

OBJECTIVES/SPECIFIC AIMS: This presentation will highlight a structured, collaborative approach to implementing and utilizing the RPPR process created at the University of Minnesota CTSI in response to the need to enhance the quality, efficiency, consistency, and utilization of annual program reporting. The approach is in line with the NCATS’s strategic objective that encourages all CTS organizations to “disseminate research results and best practices broadly, and promote a culture of openness, sharing and transparency” (NCATS, 2016, p. 19). Program activities that support translational processes and contribute to clinical outcomes are complex, nonlinear, and multidisciplinary (Smith etal., 2017). In this complex context, the meaningful engagement and reflection of program staff and collaborators is essential for all aspects of program planning, implementation, reporting, and dissemination. The University of Minnesota CTSI’s key objectives, goals, and uses of RPPR are as follows: - Develop, align, and leverage the RPPR to fulfill the accountability requirements, needs, and expectations of multiple stakeholders: NIH/NCATS, Internal Advisory Board and External Advisory Board, campus/hub, program staff and collaborators. - Engage the CTSA staff and collaborators as a team in multiple aspects of program reporting. - Inform strategic management, continuous improvement, monitoring and evaluation, organizational learning and dissemination to program stakeholders. - Translate the reported information into practical, evidence-based issues and strategic questions for the leadership discussions and advisory board consultations, actionable work plans, communication to stakeholders, organizational learning, and translational science knowledge base. METHODS/STUDY POPULATION: A case study of the programmatic/evaluative and methodological approach/technique development that resulted in a formal, structured, collaborative, transparent process with detailed guidelines, templates, and timelines. The process and content for reporting has been developed via a variety of methods and sources: specific funder (NIH) requirements, Huddle meetings, document/content/database analysis, reflection meetings with component staff, informal conversations, and observations. Preparation for the report began almost one year in advance, including careful analysis of the report requirements, developing user-friendly, detailed guidelines, templates, and examples. The guide templates and worksheets were created as a result of time spent navigating current instructions provided by NIH and NCATS. Timeline/project plan was developed with start and end dates for all of the moving parts along with identified responsible personnel for each of the tasks. A grid of the grant components and responsible personnel was designed to highlight the matrixed organization of the grant and the need to work across components to create single reports. The RPPR key categories have also been considered for incorporating and tracking in a program activity/customer tracking system for ongoing data management and use. As a complex translational science program, UMN CTSI has multiple initiatives, variables, and metrics to report. The program staff has been deeply engaged in the evaluative reflection to identify, prioritize, and incorporate into the RPPR the metrics that most useful to manage and describe CTSI processes, participation, products, and outcomes. Program components responded differently to the collaborative approach implemented. The M&E technical assistance was implemented in 3 different ways: components either did the M&E RPPR template themselves, with minimal M&E team assistance; responded to comments and information provided by the M&E team as a first step; or requested a significant level of assistance from M&E. Participants/partners in developing and using RPPR include CTSI program leadership and staff, administration, communication staff, M&E team, and our collaborators. RESULTS/ANTICIPATED RESULTS: The proposed comprehensive approach to the annual program performance reporting shows sound promise to enhance program staff engagement, report utilization, learning, strategic management, self-evaluation capacity, and continuous improvement within a clinical and translational science organization. DISCUSSION/SIGNIFICANCE OF IMPACT: This structured approach’s impact is significant in that it fills the current gap in the practice, literature, and methodology and offers a practical example of a “practice that works” for CTR (and other) organizations and programs striving to improve their reporting practices, staff engagement, learning, and program impact. Leveraging and synergizing the RPPR requirements and other complex, data-demanding obligations and needs can help the CTS programs move beyond the once-a-year compilation of project accomplishments and challenges to developing and sharing a thoughtful translational science program success story. References: National Center for Advancing Translational Sciences. (2016). NCATS Strategic Plan. NIH. Available at: https://ncats.nih.gov/strategicplan Smith, C., Baveja, R., Grieb, T., & Mashour, G. (2017). Toward a science of translational science. Journal of Clinical and Translational Science, 1(4), 253-255. doi: 10.1017/cts.2017.14

OBJECTIVES/GOALS: Designed sampling from databases (DSD) methods have been used to cross-check electronic medical records for errors, structure study design, and, we hypothesize, can be used to make data collection for surgical quality metrics more efficient, particularly within national databases. We plan to apply statistical and DSD methods to accomplish the following aims:

1. 1. Identify the most important elements in managing post-operative pain

2. 2. Identify the most informative procedure or population-based targets to focus collection of additional, labor-intense detail surrounding adequacy of pain control (i.e., Patient Reported Outcome Measures (PROMs)).

METHODS/STUDY POPULATION: Our study population includes all children, ages 1-18 years, captured in the National Surgical Quality Improvement Project-Pediatric (NSQIP-P) from 2019 to 2021. We plan to apply statistical (regression modeling) and DSD methods to accomplish the aims listed above. RESULTS/ANTICIPATED RESULTS: For Aim 1, we expect to identify patient, procedure, and perioperative pain management practices that influence postoperative pain. For Aim 2, we will focus on outcomes such as PROMs that are challenging to obtain. By applying DSD methods, we will identify specific procedure and/or population-based cohorts to capture PROMs and decrease data collection burdens, while maintaining power, as the project is scaled nationally to all of NSQIP-P. DISCUSSION/SIGNIFICANCE OF IMPACT: Data from this study will inform expansion of NSQIP-P to collect novel outcomes of clinical and societal importance without prohibitively increasing data collection burden.

ABSTRACT IMPACT: Understanding the mechanism underlying the DASH diet may shed light on the physiologic process by which nutrition influences blood pressure and potentially lead the way to new therapeutics that target ion channels. OBJECTIVES/GOALS: Hypertension is a disease of the westernized world, as it stems from lifestyle habits. Lower salt consumption reduces blood pressure, yet DASH diet is much more effective, lowering blood pressure as efficiently as one anti-hypertensive drug. The precise mechanism through which DASH achieves its effect is not understood, and this is the project goal. METHODS/STUDY POPULATION: We hypothesize that exposing hypertensive volunteers to a high potassium and low sodium DASH diet will change the composition of renal ion channel in an aldosterone-dependent manner, leading to excretion of both sodium and potassium and a reduction in blood pressure. To assess how the nutritional change changes ion channel composition in the kidneys’ epithelium in aldosterone-induced manner, we will monitor urine exosomes, which contain epithelial cell membranes. We designed an in-hospital nutritional studies recruiting 20 volunteers. Patients will consume carefully designed menu, and measurements will be collected daily: blood pressure, biologic samples including blood and urine electrolytes, aldosterone, and urine for exosomes. RESULTS/ANTICIPATED RESULTS: We have collected data from 5 research volunteers so far.following exposure to the high potassium diet, Aldosterone blood levels increased while blood level of both potassium and sodium was maintained within normal limits. Urinary ratio of electrolytes, sodium:potassium was reversed 5-7 days following nutritional change from 6 to 1. Both manual and automated 24-hour blood pressure measurements confirmed blood pressure reduction following nutritional change. The following illustrates the impact the diet had on a participant’s 24-hour ambulatory blood pressure. Daily mean blood pressure was reduced from 120/76 mmHG to 112/68, mean awake blood pressure was reduced from 125/80 mmHG to 117/72 mmHG, and mean sleep blood pressure was reduced from 112/69 to 103/60 mmHG DISCUSSION/SIGNIFICANCE OF FINDINGS: Understanding the mechanism underlying the DASH diet may shed light on the physiologic process by which nutrition influences blood pressure and potentially lead the way to new therapeutics that target ion channels. By introducing our participants to a healthier lifestyle, they could maintain lower blood pressure without requiring medication.

Implementation of clinically useful research discoveries in the academic environment is challenged by limited funding for early phase proof-of-concept studies and inadequate expertise in product development and commercialization. To address these limitations, the National Institutes of Health (NIH) established the National Centers for Accelerated Innovations (NCAI) program in 2013. Three centers competed successfully for awards through this mechanism. Here, we present the experience of one such center, the Boston Biomedical Innovation Center (B-BIC), and demonstrate its remarkable success at the translation of innovations to clinical application and commercialization, as well as skills development and education.

OBJECTIVES/GOALS: In this study, we aim to report the role of porins and blaCTX-M β-lactamases among Escherichia coli and Klebsiella pneumoniae, focusing on emerging carbapenem resistant Enterobacterales (CRE) subtypes, including non-carbapenemase producing Enterobacterales (NCPE) and ertapenem-resistant but meropenem-susceptible (ErMs) strains. METHODS/STUDY POPULATION: Whole genome sequencing was conducted on 76 carbapenem-resistant isolates across 5 hospitals in San Antonio, U.S. Among these, NCP isolates accounted for the majority of CRE (41/76). Identification and antimicrobial susceptibility testing (AST) results were collected from the clinical charts. Repeat speciation was determined through whole genome sequencing (WGS) analysis and repeat AST, performed with microdilution or ETEST®. Minimum inhibitory concentrations (MIC) were consistent with Clinical and Laboratory Standards Institute (CLSI M100, ED33). WGS and qPCR were used to characterize the resistome of all clinical CRE subtypes, while western blotting and liquid chromatography with tandem mass spectrometry (LC-MS-MS) were used to determine porin expression and carbapenem hydrolysis, respectively. RESULTS/ANTICIPATED RESULTS: blaCTX-Mwas found to be most prevalent among NCP isolates (p = 0.02). LC-MS/MS analysis of carbapenem hydrolysis revealed that blaCTX-M-mediated carbapenem hydrolysis, indicating the need to reappraise the term, “non-carbapenemase (NCP)®” for quantitatively uncharacterized CRE strains harboring blaCTX-M. Susceptibility results showed that 56% of all NCPE isolates had an ErMs phenotype (NCPE vs. CPE, p < 0.001), with E. coli driving the phenotype (E. coli vs. K. pneumoniae, p < 0.001). ErMs strains carrying blaCTX-M, had 4-fold more copies of blaCTX-M than ceftriaxone-resistant but ertapenem-susceptible isolates (3.7 v. 0.9, p < 0.001). Immunoblot analysis demonstrated the absence of OmpC expression in NCP-ErMs E. coli, with 92% of strains lacking full contig coverage ofompC. DISCUSSION/SIGNIFICANCE: Overall, this work provides evidence of a collaborative effort between blaCTX-M and OmpC in NCP strains that confer resistance to ertapenem but not meropenem. Clinically, CRE subtypes are not readily appreciated, potentially leading to mismanagement of CRE infected patients. A greater focus on optimal treatments for CRE subtypes is needed.

ABSTRACT IMPACT: Currently, there are no medications to treat metabolic syndrome and our research sheds light on a potential therapeutic that could prove beneficial for this disease that affects one-third of the US population. OBJECTIVES/GOALS: Our goal was to determine the role of the GI tract in MetS, specifically how approved GI-directed medications affect metabolic parameters. Thus, we assessed the effects of mesalamine, a common therapeutic utilized to treat mild to moderate UC, on metabolic parameters in comorbid UC and MetS patients METHODS/STUDY POPULATION: This was a retrospective study with data extracted from Cerner’s HealthFacts database across the United States (US). Inclusion criteria included adult patients (≥18 years old) with a diagnosis of UC and at least 3 of the 5 metabolic risk factors which included i) dyslipidemia, ii) low HDL, iii) hyperglycemia, iv) hypertension, and v) increased abdominal obesity as determined by elevated BMI. A total of 6197 patients across the US between the years of 2007 and 2017 were included. We pulled patients who had a mesalamine prescription within +/- 7 days of an encounter in which they were diagnosed with UC (index date) and the closest values to 3 and 12 months after the index date. Mean age for patients was 53.8 ±19.9, with predominance of female sex (52.9%) and white race (78.0%). RESULTS/ANTICIPATED RESULTS: There was an observed reduction in BMI, fasting glucose, and increase in HDL levels post start of mesalamine treatment along with a decrease in inflammatory markers (ESR and CRP) (p<0.001). DISCUSSION/SIGNIFICANCE OF FINDINGS: The GI tract contributes to numerous disorders associated with metabolic dysfunction. Our retrospective analysis revealed mesalamine treatment in comorbid UC and MetS patients improved metabolic parameters, providing evidence that targeting the GI tract in these individuals potentially improves dysregulated metabolic processes.