OBJECTIVES/GOALS: The ITHS TL1 program is designed to grow trainees’ competence and knowledge in translational research. Our objective is to expand the program to the 5-state Washington, Wyoming, Alaska, Montana, and Idaho (WWAMI) region by establishing a TL1 cohort at Montana State University (MSU). METHODS/STUDY POPULATION: Interdisciplinary training at the predoctoral level is ideal for preparing the future translational workforce. At this stage in their training, they have developed disciplinary expertise but have not yet narrowed their specializations. By expanding the TL1 program to include both University of Washington (UW) and MSU we are amplifying the robust academic research networks of both institutions, particularly programs in rural health equity, rural and tribal populations, and emerging infectious diseases. Using a collaborative, online educational model we will bring together trainees in a multi directional, joint training effort utilizing existing and emerging collaborations. RESULTS/ANTICIPATED RESULTS: The anticipated outcome is to create a single program by bringing together a cohort of scholars from various disciplines spanning the translational science spectrum, with diverse types of research experience which enables them to learn from each other in a diverse setting. This will allow the program to more effectively grow trainee’s competencies and knowledge in multidisciplinary translational research methodology, as well as build skills in team science and cross-disciplinary communication. DISCUSSION/SIGNIFICANCE: If successful, the ITHS TL1 program will prepare translational scientists with an awareness of diverse perspectives and contemporary research challenges. This would benefit the 5 state WWAMI region, which covers 27% of the total land mass of the US.

OBJECTIVES/SPECIFIC AIMS: We sought to investigate the role of the host microbiome during severe, acute respiratory infection (ARI) to understand the drivers of both acute clinical pathogenesis. METHODS/STUDY POPULATION: Nasopharyngeal swabs comprised of mixed cell populations at the active site of infection were collected from 192 hospitalized pediatric patients with ARI. We combined comprehensive respiratory virus detection and virus genome sequencing with 16S rRNA gene sequencing to evaluate the microbial content of the airway during ARI. This data was coupled with 11 clinical parameters, which were compiled to create a clinical severity score. The microbiome profiles were assessed to determine if clinical severity of infection, and/or specific virus was associated with increased clinical severity. RESULTS/ANTICIPATED RESULTS: We identified 8 major microbiome profiles classified by dominant bacterial genus, Moraxella, Corynebacterium, Staphylococcus, Haemophilus, Streptococcus, Alloiococcus, Schlegelella, and Diverse. Increased clinical severity was significantly associated with microbiome profiles dominated by Haemophilus, Streptococcus, and Schlegelella, whereas Corynebacterium and Alloiococcus were more prevalent in children with less severe disease. Independent of the microbial community, more than 60% of patients with the highest clinical severity were infected with either respiratory syncytial virus or rhinovirus. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results indicate that individually and in combination, both virus and microbial composition may drive clinical severity during acute respiratory viral infections. It is still unclear how the complex interplay between virus, bacterial community, and the host response influence long-term respiratory impacts, such as the development of asthma. Nonetheless, during ARIs therapeutic interventions such as antibiotics and probiotics may be warranted in a subset of patients that are identified to have both a virus and microbiome profile that is associated with increased pathogenesis to limit both acute and long-term phenotypes.

Objectives/Goals: To identify the genomic mechanisms underlying cross-species regulation of longevity among mammals and birds and to characterize the impact of those conserved pathways on human aging. More broadly, this study aims to develop a novel evolutionary approach to understand the genetics of complex traits. Methods/Study Population: High-quality genome sequences for 194 bird species and 295 mammal species with reliable longevity and body size data were obtained from publicly available resources. The data include coding sequence alignments of 16,863 mammalian and 14,565 avian one-to-one orthologous genes. Gene-wise relative evolutionary rates (RERConverge) and maximum likelihood phylogenetics (PAML) were computed to assess for evidence of purifying selection and positive selection for longevity. As part of ongoing analysis, human orthologs of selected results will be examined in the UK Biobank for validation. Results/Anticipated Results: Preliminarily, we have found a signal of concordant positive selection between two classes of vertebrates separated by hundreds of millions of years. Several genes show signals of positive selection in long-lived species of both birds and mammals. Ongoing work focuses on elucidating the relationship between relative evolutionary rates and positive selection, the overlap in selection signature between long-lived animals with large body sizes and those who are exceptionally long lived for their body size, and further elaborating on convergence between mammals and birds. Discussion/Significance of Impact: Currently, most scientific knowledge about aging is from experiments on short-lived model organisms. By systematically studying the genomes of long-lived mammals and birds, we aim to develop a new method for studying complex traits and uncover novel insights into the mechanisms of longevity.

OBJECTIVES/GOALS: Evaluate the migration and immune suppressive functions of CCR2+/CX3CR1+ myeloid-derived suppressor cells (MDSCs). Integrate experimental data and biologically relevant mathematical models of infiltrating MDSCs in the context of glioblastoma (GBM). METHODS/STUDY POPULATION: CCR2+/CX3CR1+ cells were enriched from bone marrow obtained from CCR2(+/RFP)/CX3CR1(+/GFP) glioma-bearing mice to evaluate their immune-suppressive phenotype and ability to migrate to CCL2 and CCL7. Fluorescent imaging and quantification were performed on a range of tumor sizes to acquire vasculature, tumor, T cell, and MDSC densities. A system of ordinary differential equations was constructed to represent the temporal dynamics of glioma cells, T cells, and MDSCs within the tumor microenvironment. The Approximate Bayesian Computation method was used to determine probability distributions of important parameters, such as the suppression rate of T cells by MDSCs. RESULTS/ANTICIPATED RESULTS: CCR2+/CX3CR1+ M-MDSCs isolated from the bone marrow of tumor-bearing mice suppress CD8+ T cell proliferation and IFNγ production. CCR2+/CX3CR1+ cells migrate to recombinant and KR158B glioma sourced CCL2 and CCL7. Parameter values determined by the Approximate Bayesian Computation method agreed with parameter values from experimental data. This result further validated the structure and results of the mathematical model when performing computer simulations; thus, we can predict CCR2+/CX3CR1+ M-MDSC infiltration over time. DISCUSSION/SIGNIFICANCE: The immune-suppressive microenvironment in GBM contributes to poor outcomes despite standard of care. This study integrates biological and mathematical models to better understand infiltrating immune-suppressive cells, namely CCR2+/CX3CR1+ M-MDSCs. Future directions include modeling immunotherapies.

OBJECTIVES/SPECIFIC AIMS: Industry payments to physicians can present a conflict of interest. The Physician Payments Sunshine Act mandates the disclosure of these financial relationships to increase transparency. Recent studies in other surgical specialties have shown that research productivity is associated with greater industry funding. In this study, we characterize the relationship between academic influence and industry funding among academic gynecologic oncologists. METHODS/STUDY POPULATION: Departmental websites were used to identify academic gynecologist oncologists and their demographic information. The Hirsch index (h-index) relates an author’s number of publications to number of times referenced by other publications, a validated measure of an author’s academic influence. This was obtained from the Scopus database. The Center for Medicaid and Medicare Services Open Payments online database was searched for all industry payments in 2017. The NIH Reporter online database was searched for active grants. Goodness of fit testing showed that all variables followed nonparametric distributions. Medians were compared using Mann-Whitney U tests and Kruskal-Wallis analysis of variance with post-hoc Dunn’s test. RESULTS/ANTICIPATED RESULTS: Four hundred and sixty-six academic gynecologic oncologists were included in the analysis. In 2017, 89.7% of this group received industry funding totaling $41.4 million. Median industry funding was $453 [IQR $67-19684] and median h-index was 14 [IQR 8-26]. Only 8.1% of gynecologic oncologists were NIH grant recipients and they received significantly higher industry payments ($357 vs. 11,168, P<0.01). Gender and academic rank were not associated with industry funding. Gynecologic oncologists in the highest decile of industry funding received a median payment of $447,651[N=46, IQR $285,770 – 896,310] totaling $36.5 million. The median h-index for this top-earning decile was 23 [N=46, IQR 16.5-30.3]. When stratified by payment amount, median h index increased but only reached statistical significance in the highest cohort receiving >$100,000 (N = 63, P<0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: The majority of academic gynecologic oncologists receive industry funding although there are large variations in payments. Those receiving the largest payments are more likely to hold NIH grants and have greater academic influence.

OBJECTIVES/SPECIFIC AIMS: Interleukin-23 (IL-23) promotes differentiation of naïve T-cells into Th17 cells, which drive the pathogenesis of autoinflammatory conditions such as psoriasis. IL-23-neutralizing antibody therapies are now in use for treatment of psoriasis, with promising results. Studies in mice have shown that IL-23 plays a role in inhibiting the growth, progression, and metastasis of melanomas. Thus, therapeutic neutralization of IL-23 in patients may inadvertently increase their susceptibility to development of melanoma. In this study, we aim to characterize expression of IL-23 receptors (IL-23R) in human melanocytes and melanoma cells and tissue and to study the effect of IL-23 on growth, proliferation, and tumorigenicity of these cells. METHODS/STUDY POPULATION: IL-23R expression was characterized using immunofluorescence staining, Western blot, and flow cytometric analysis. Response of melanoma and melanocytes to recombinant IL-23 treatment will be studied through similar methods in addition to assays of cell proliferation and tumorigenicity. RESULTS/ANTICIPATED RESULTS: Preliminary immunofluorescence staining and flow cytometry results indicate that both human melanoma and primary melanocytes express IL-23 receptors. Western blot analysis showed that melanoma cell line A375 expressed nearly twice the amount of IL-23R versus normal melanocytes (p<0.05). Based on previous studies, we anticipate that addition of recombinant IL-23 to cultures of melanoma will reduce proliferative potential, and we expect similar addition to normal melanocytes will increase DNA repair mechanisms. DISCUSSION/SIGNIFICANCE OF IMPACT: In showing that human melanocytes and melanoma cells express IL-23 receptors, and potentially showing the inhibitory effect of IL-23 in the development of melanocytic neoplasms, our findings imply that using IL-23 neutralizing therapies may increase risk of developing melanoma, especially in patients who are already susceptible. As such, these therapies must be used with great care in these patients.

Objectives/Goals: Quantify environmental persistence and airborne stability of avian (aMPV) and human metapneumovirus (hMPV) and evaluate far-UVC light (at 222 nm) as a safe, non-chemical disinfection method to reduce viral transmission in agricultural and healthcare environments. Methods/Study Population: Subtypes A and B of aMPV and subtype B of hMPV isolates will be propagated in Vero and LLC-MK2 cells, respectively. Viral persistence will be quantified on fomites under varying temperature and humidity. Aerosol stability will be assessed using an environmental chamber and an atomizer system. Once baseline survival is established, samples and aerosols will be exposed to different far-UVC doses, intensities, and durations. The endpoints will be determined by observing cytopathic effects (CPE), virus titers will be calculated by the Karber method, and titers will be expressed as TCID50. Results/Anticipated Results: We anticipate quantifying surface and aerosol stability profiles of aMPV and hMPV across several porous and non-porous materials (fomites) and environmental conditions relevant to poultry and clinical settings. Far-UVC exposure is predicted to achieve rapid viral inactivation on non-porous surfaces and in aerosols without measurable cytotoxicity or material degradation. The findings will establish disinfection thresholds and demonstrate the practicality of far-UVC integration into real-world agricultural and healthcare biosecurity systems. Discussion/Significance of Impact: This work advances One Health biosecurity by establishing safe far-UVC disinfection protocols to control the spread of both aMPV and hMPV. Findings will inform infection control policies and reduce economic and health burdens in poultry operations and vulnerable human populations.

ABSTRACT IMPACT: Summarize the burden of diabetes comorbidities and its impact in healthcare utilization in Puerto Rico OBJECTIVES/GOALS: To estimate the prevalence of common comorbidities and describe the healthcare utilization patterns in patients with type 2 diabetes mellitus (T2DM) in Puerto Rico. METHODS/STUDY POPULATION: This is a descriptive study using healthcare claims data from patients with T2DM (based on ICD-9 diagnosis code) from most public and private healthcare insurance companies providing services in Puerto Rico in 2013 (representing more than 90% of insured population). Descriptive analyses by age, sex, type of insurance, health region, and type of medical encounter were done using frequency and percent for categorical data or means or median (with corresponding standard deviation or interquartile range) for continuous variables RESULTS/ANTICIPATED RESULTS: A total of 3,100,636 claims were identified from 485,866 adult patients with T2DM. Most patients were women (276,400; 57%), older than 65 years (235,390; 48%), from the Puerto Rico health regions of Caguas (79,604; 16%), Metro (66,280; 14%), or Bayamon (62,673; 13%) with private health insurance (371,806; 77%). The number of claims per patient ranged from 1 to 339. A mean of 6.3 claims (SD ±9.99) and a median of 3 claims (Q1 1- Q3 8) per subject were identified. Most (74%) were related to the diagnosis of diabetes (1,829,2015; 59%) or to cardiovascular diseases (458,219; 15%) and associated to outpatient services (2,722,727; 88%). The most prevalent comorbidities were hypertension (235,277; 48%), hyperlipidemia (197,449; 41%), neuropathy (100,471; 21%); renal disease (71,517; 15%), and retinopathy (61,837; 13%) DISCUSSION/SIGNIFICANCE OF FINDINGS: A high prevalence of comorbidities and use of healthcare services were identified in patients with T2DM, especially in older adults. Most comorbidities were due to diabetes-related conditions, highlighting the importance of early diagnosis and adequate management of T2DM patients to avoid preventable burden to the patient and the healthcare system

Objectives/Goals: Mass incarceration, i.e., extremely high rates of incarceration concentrated in impoverished racially segregated communities, is associated with poor neighborhood health, but it is unclear if this is due solely to formerly incarcerated individuals. We examine these population health effects through neighborhood premature mortality rates. Methods/Study Population: We calculated census tract-level overall, gender-, and race-specific age-adjusted premature mortality rates using mortality data (2010-2014) from the New York City Department of Health. We excluded tracts with subgroup population <800. Exposure was the NY State imprisonment rate (2010), modeled as quintiles. As covariates, we included % non-Hispanic Black; poverty, education, and violent crime rates; and population density. We used GLM regression models with the census tract as the unit of analysis. To test if spatial clustering of incarceration (i.e., high-incarceration census tracts surrounded by high-incarceration census tracts) was associated with premature mortality rate independent of covariates and tract incarceration rate, we used LISA cluster values and proximity to high-high clusters. Results/Anticipated Results: Across 1985 tracts, incarceration rate ranged from a median of 19 (quintile 1) to 698 (quintile 5) per 100,000 people. In unadjusted models, neighborhoods in Q5 of incarceration rate had 2.4x higher rate ratios of premature mortality versus Q1. In fully adjusted models, Q5 tracts had 62% higher rate ratios (aOR 1.62, 95% CI 1.50-1.75; P<0.001), sex-specific findings were similar for males and females, Black and Hispanic (aOR 1.36; 95% CI 1.04-1.78 and aOR 1.49, 95% CI 1.24-1.79, specifically) rate ratios were both P<0.001 but Asian and White were NS. Being in a high-high cluster was significantly associated with premature mortality independent of covariates and tract incarceration rate (aOR 1.13, 95% CI 1.06-1.20), whereas low-low clusters were protective (aOR 0.90, 95% CI 0.85-0.94), both P<0.001. Discussion/Significance of Impact: Premature mortality rates are substantially higher in high-incarceration neighborhoods even accounting for confounders. Sex-specific findings suggest spillover to never-incarcerated people, and race-specific findings suggest concentration in social networks of the incarcerated. Spatial analyses suggest true neighborhood-level effects.

OBJECTIVES/SPECIFIC AIMS: The main aim of this study was to investigate the relationship between measures of adiposity and FGF-23 in a sample of patients with CKD stages 3-4. METHODS/STUDY POPULATION: This study was a clinic-based cross-sectional investigation of 71 CKD patients who underwent body composition and anthropometric assessments as part of the relationship of insulin sensitivity in kidney disease and vascular health (RISKD) study. Dual energy x-ray absorptiometry (DEXA) scans were used to measure total fat mass and body mass index (BMI) was computed using baseline weight and height measurements. Biomarkers included serum FGF-23 (C-terminal), serum leptin, high sensitivity C-reactive protein (hsCRP), serum triglycerides, high density lipoprotein (HDL) cholesterol and total cholesterol. Creatinine-based estimated glomerular filtration rate (eGFR) was computed using the CKD-EPI equation. Multiple linear regression with robust standard errors was used to investigate the relationship between FGF2-3 and measures of adiposity (BMI, total fat mass and serum leptin). Log-transformation was performed for variables (FGF-23, hsCRP and serum lipids) with considerable skewness. RESULTS/ANTICIPATED RESULTS: The median age of the study participants was 68 (IQR: 60, 73) years; 26% were female and 23% were African-American. Median eGFR was 46.9 ml/min/1.73m2 (IQR: 41.9, 52.8), median BMI was 31 kg/m2 (IQR: 27, 35). Log FGF-23 had a significant positive correlation with BMI (r = 0.27, p = 0.02), total fat mass (r = 0.30, p = 0.01) and serum leptin (r = 0.43, p < 0.0001). After full adjustment for age, sex, race, eGFR, log hsCRP, log HDL and log triglycerides, a 50% increase in FGF-23 was associated with a 1 kg/m2 [95% CI: 0.1, 1.9; p = 0.03] increase in BMI, a 2.5 kg [95% CI: 0.2, 4.8; p = 0.03] increase in total fat mass and a 6.7 ng/mL [95% CI: 1.0, 12.4; p = 0.02] increase in serum leptin. DISCUSSION/SIGNIFICANCE OF IMPACT: In this sample of patients with moderate-to-severe CKD, we found a significant independent association between higher FGF-23 levels and higher adiposity (BMI, total fat mass and the pro-atherogenic adipocytokine, leptin). The underlying causes and the implications of these associations− particularly in bone and vascular health− need to be further investigated.

OBJECTIVES/SPECIFIC AIMS: The objective of this study is the pharmacology of sublingual Buprenorphine in Hispanics/Latino men and women. Specifically we plan to: (1) Administer sublingual buprenorphine to Hispanic/Latino men and women volunteers, and measure the circulating amounts of the drug in the bloodstream as a function of time; that is, pharmacokinetics of buprenorphine. The goal of the proposed study is to evidence that there are gender and ethnic differences in the pharmacokinetics of sublingual buprenorphine between not only Hispanics/Latinos and non-Hispanics/Latinos (Caucasian), but also within Hispanic/Latino men and women. METHODS/STUDY POPULATION: We are proposing a phase 1 of buprenorphine using 12 healthy volunteers. To test for differences in pharmacokinetics between Hispanic/Latino men and women, 6 Hispanic/Latino men, and 6 Hispanic/Latino women 21 years of age and older will be recruited. The volunteers should be living in Puerto Rico, and must have both parents born in Puerto Rico. Sublingual buprenorphine will be administered using a low dose of 16 mg one time only. Blood samples will be collected from each volunteer at t=0, 1, 2, 4, 6, 8, 12, and 24 hours after administration. The amount of circulating drug in the bloodstream of the volunteers will be measured using liquid chromatography combined with mass spectrometry. Pharmacokinetic obtained parameters will be maximal plasma concentration, minimal plasma concentration, predose concentration, 24 hour post predose concentration, the time for maximum concentration. The area under the curve will be determined by the trapezoidal rule. Male Versus female data will be compared using 2-tailed t-test. RESULTS/ANTICIPATED RESULTS: We anticipate that: (1) Hispanic/Latino women will have longer circulating times of the drug in the bloodstream and higher maximum concentrations, compared with men. (2) Hispanic/Latino men and women will have higher amounts of the circulating drug, compared with already reported pharmacokinetic data of non-Hispanic Caucasian men. DISCUSSION/SIGNIFICANCE OF IMPACT: Gender differences have been elucidated in the prevalence rates of substance abuse, health service utilization, treatment outcomes, and physiological consequences of drug consumption in the United States. It is known that in general, women progress from drug use to dependence must faster than men; women also suffer more severe physical and emotional consequences than men, yet women seek treatment for drug addiction in lower rates compared with men. Women also show lower pharmacological treatment effectiveness as they are less likely to feel satisfied upon entering a substance abuse treatment and they show higher cravings. Sublingual buprenorphine is a very popular and relatively new medication used primarily for opiate addiction since 2002. Gender differences have been elucidated in the pharmacology of buprenorphine sublingual tablets used for the treatment of opioid addiction. One study showed that women had higher concentrations of circulating parent drug and it is metabolites compared with men. One metabolite in particular norbuprenorphine was found in almost double the plasma concentration in women. Interestingly, gender differences were not pursued at all by the Pharmaceutical Company sponsoring the approval of the sublingual Buprenorphine by the FDA. The cytochrome enzyme CYP 3A4 responsible for the metabolism of Buprenorphine has higher activity in Caucasian/African American women compared with men. However these studies failed to design and recruit significant amount of patients with Hispanic ethnicity to adequately elucidate the gender differences within this ethnic group. Higher plasma concentrations and longer circulation times of a drug may result not only in lower efficacy outcomes but also higher toxicity and undesired effects. Unfortunately, the lack of pharmacological effectiveness and lack of satisfaction in women undergoing drug treatment programs has not been adequately studied to understand the gender difference in pharmacological treatment outcomes between Hispanic/Latino men and women. Due to the under-representation of Hispanic/Latino men but most importantly women in s studying the pharmacology of sublingual Buprenorphine, and considering the well-established gender difference of the principal enzyme (CYP 3A4) responsible for the pharmacology of Buprenorphine, we are proposing a pilot study of the pharmacology of sublingual Buprenorphine in Hispanic/Latino volunteers living in Puerto Rico with equal number of male and female patients. We expect our research to clinically and scientifically elucidate the gender differences of sublingual buprenorphine for opioid addiction in Hispanics/Latinos. The outcome of such research will be the foundation of subsequent clinical studies that aim in updating the current standard of care for Hispanic/Latino men and women that require therapy for opioid addiction.

OBJECTIVES/SPECIFIC AIMS: Assess the presence of contact activation at baseline in sera from common variable immunodeficiency (CVID) patients with and without inflammatory complications compared with healthy controls. METHODS/STUDY POPULATION: CVID patients were recruited in the outpatient setting and the measurement of cleaved plasma HK (cHK) levels was determined by Western blot analysis, under reducing conditions, with quantitation of total and cHK bands using an Odyssey imaging system (Licor). One-way ANOVA test for differences among the 3 studied groups will be applied. Biomarkers C3, C4, C1 inhibitor levels and hs-CRP were also measured. RESULTS/ANTICIPATED RESULTS: Participant enrollment continues and to date, 9 CVID patients were studied, 7 with and 2 without inflammatory complications. Repeated determinations of cleaved HK% (cHK%) revealed an average of 1.20% (range: 0.46%–2.66%) in CVID patients with inflammatory complications and those without complications averaged 1.07% (range: 0.79%–1.35%). Healthy controls had an average cHK of 1.15% (range: 0.60%–2.10%). DISCUSSION/SIGNIFICANCE OF IMPACT: Cleaved kininogen detected in the sera of CVID patients was found at similar levels compared with healthy controls (cHK<5%). Findings suggest that systemic activation of the contact system might be absent in CVID, however, future considerations include developing detection methods for local tissue activation.

ABSTRACT IMPACT: Through a comprehensive analysis of patterns of care and outcomes in Veterans with chronic myelomonocytic leukemia, we will identify Veteran-specific determinants of survival that will allow for more personalized decision-making in this underserved population. OBJECTIVES/GOALS: Little is known about outcomes of Veterans with chronic myelomonocytic leukemia (CMML), a malignancy with high morbidity and mortality. In this study, we will describe patterns of care, identify factors that impact survival, and compare outcomes in this cohort to those of the civilian population. METHODS/STUDY POPULATION: We will conduct a comprehensive retrospective review of approximately 1,000 Veterans with CMML. We will construct a database of demographics, clinical characteristics, disease characteristics, treatment regimens, and outcomes in this cohort. Adult Veterans with a diagnosis of CMML determined by ICD-O-3 coding who were treated through the VA after 1990 and have sufficient electronic health data will be included in this study. Veterans receiving the majority of their care for CMML at non-VA hospitals or clinics will be excluded. Data on veterans will be obtained and validated from VA clinical databases and chart review. Data on the civilian population will be obtained from SEER registries. RESULTS/ANTICIPATED RESULTS: We will first describe the baseline patient characteristics and distribution of disease in this cohort and illustrate the landscape of their CMML care. We will subsequently describe the impact of baseline patient characteristics on pathological features of disease, patterns of care, response to therapy, and survival. We anticipate we will identify several Veteran-specific factors that influence treatment and are prognostic or predictive of survival. After drawing conclusions about the Veteran cohort alone, we will compare baseline characteristics and survival outcomes between the Veteran and civilian populations. We predict we will identify significant differences between these two cohorts. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study will help inform Veteran care by identifying clinical features and patient characteristics that are prognostic or predictive of survival. This will open the door for more accurate risk stratification and personalized treatment that could improve outcomes in this underserved population.

OBJECTIVES/GOALS: 5-nitroimidazoles are the only FDA-approved medications for T. vaginalis treatment. Resistance has been observed in 5-10% of cases, but may be rising. We aimed to delineate mechanisms of resistance in isolates of T. vaginalis using transcriptome profiling of resistant and sensitive T. vaginalis isolates. METHODS/STUDY POPULATION: T. vaginalis isolates (4 metronidazole (MTZ)-resistant were grown in triplicate in Diamond’s Trypticase-Yeast-Maltose medium. MTZ susceptibility testing confirmed MTZ MLCs of T. vaginalis isolates. Total RNA extraction was done using Trizol reagent (Invitrogen; Carlsbad; CA); according to the manufacturer’s instructions. RNA sequencing (RNAseq) and bioinformatics analyses were performed to identify significantly differentially expressed genes (DEGs) in MTZ-resistant vs. sensitive isolates. Subsequent qPCR was performed to confirm and extend RNAseq data and gene targets related to 5-nitroimidazole resistance. RESULTS/ANTICIPATED RESULTS: RNAseq identified key DEGs in MTZ-resistant vs. sensitive isolates. DEGs from MTZ-resistant isolates included those involved in metabolic pathways relevant to 5-nitroimidazole resistance such as energy production (glycolytic enzymes) and oxygen-scavenging (thioredoxin). Other DEGs included those encoding transcription factors (MYB DNA-binding protein), ribosomal proteins (30S, 40S, 50S, 60S), protein kinases (CAMK, ser/thr, CMGC), Ankyrin repeat proteins, surface proteins (Surface antigen BspA-like) and various uncharacterized hypothetical proteins. RT-qPCR experiments confirmed reduced expression of genes encoding ferredoxin (drug activation) and flavin reductase 1 (oxygen scavenging) in MTZ-resistant T. vaginalis isolates as compared to MTZ-sensitive isolates. DISCUSSION/SIGNIFICANCE: In this study, we identified several DEGs in resistant T. vaginalis isolates. Further studies with large number of isolates representing a broad range of MTZ-susceptibility patterns are needed to identify genes that may represent new targets for future drug development.

Objectives/Goals: The aim of the study is to identify resistance factors for substance use (i.e., factors that explicitly help to avoid or reduce drug use). Identification of resistance factors could inform strategies that seek to reduce the prevalence of substance use and related disorders. Methods/Study Population: Adult twins aged 30–70 years were recruited from the Mid-Atlantic Twin Registry. A mixed-method approach, group concept mapping, was used to identify factors influencing participants to resist using substances. Approximately 155 participants produced 97 statements reflecting substance use resistance factors. Hierarchical cluster analysis and multidimensional scaling assessed how participants sorted and rated statements for their lifetime and current importance. Factor analysis was used to reduce data dimensionality. Reliability analyses were conducted to identify a subset of statements anticipated to consistently represent each cluster. Results were shared with participants to assess accuracy with their experiences. Results/Anticipated Results: Participants sorted 97 statements into 9 thematic clusters: (1) Controlling Personal, Negative Consequences; (2) Concern About Health and Well-being; (3) Lack of Desire; (4) Outside Influences; (5) Social Norms and My Reputation; (6) Career and Legal Impacts, (7) Avoiding Harm to Family and Relationships; (8) Preserving Family Relationships; and (9) Family and Friends Impact on Me. Participants consistently identified health concerns as an important substance use resistance factor. The statements will be further reduced to represent a smaller subset for future use as a scale to measure exposure to resistance factors. Discussion/Significance of Impact: Health concerns related to substance use were identified as an important resistance factor. This has been supported by research on smoking cessation and implemented in smoking prevention campaigns. Therefore, prioritizing health-related outcomes in prevention may be important to reduce substance use prevalence.

OBJECTIVES/GOALS: Clinical research degree program accreditation brings value to university programs situated in competitive environments. While the requirements of accreditation can be burdensome and tedious, it remains important to program growth. The objective of this project was to assess the use of REDCap for the accreditation process to reduce that burden. METHODS/STUDY POPULATION: A review of credentialing requirements was conducted to identify required data and its sources. Initial course data from a small sample of courses was collected in Excel to better assess the order of the data collection process. REDCap was then used to create a series of data collection instruments that effectively met the program evaluation data needs and customized reports for three years of course learning outcomes. The instruments were developed for its translation to other programs. Faculty, administrators, and interns participated in 2 different types of data collection activities (excel and REDCap) and evaluated the differences between the experiences. RESULTS/ANTICIPATED RESULTS: Data collection included 85 courses, with a range of 3-22 objectives that classified aligned assignments among 8 clinical research professional domains, 50 competencies, and 3 learning levels. Student outcomes data was also calculated and recorded. The time to complete the data collection process using the REDCap tool verses the excel spreadsheet per course was notably more efficient. User satisfaction was 100% improved using the REDCap tool with the average score of 8.5 out of a 1-10 scale. User comments supporting the REDCap process focused on improved time to complete and ease of process. DISCUSSION/SIGNIFICANCE: The incorporation of REDCap into data collection for program accreditation data requirements highlights the efficiency and ease of electronic data capture compared to manual entry in excel. The development of instruments makes it easy to translate to other program evaluation and accreditation needs.

OBJECTIVES/GOALS: Pursuit of independent funding by predoctoral and postdoctoral fellows requires navigating the intricate steps in preparing extramural grant applications. The Workforce Development Core of the NJ Alliance for Clinical and Translational Science (NJ ACTS) sought to evaluate an interactive grant writing group of fellows mentored by a trained coach. METHODS/STUDY POPULATION: Participants meet weekly for 3 months to develop components of a fellowship application for submission to NIH and private foundations. Sessions were moderated by a senior faculty member trained as a coach by the National Research Mentoring Network. Participant grant submission and review of the program were collected annually for the period of 2019 to 2021 as well as demographics for the 2022 cohort. RESULTS/ANTICIPATED RESULTS: Over this period, 32 predoctoral and 19 postdoctoral fellows participated in the peer review writing groups with 24 trainees currently enrolled. The peer review writing group moved to Zoom in 2020 which has enabled expansion of training to include the 3 Hub institutions and 6 additional universities. Of the 41 survey respondents, 78% submitted fellowship applications to NIH (N=28) or a non-NIH agency (N=4). Eight of these applications are currently under review or have been resubmitted for peer review. 54% of reviewed applications have been funded as NIH fellowships, diversity supplements, career grants, or non-NIH fellowships. Over 90% of participants have recommended the writing group to other trainees. DISCUSSION/SIGNIFICANCE: In conclusion, a weekly grant writing group of predoctoral and postdoctoral fellows is an effective means to receive peer review of fellowship application components and support submissions for extramural funding.

OBJECTIVES/GOALS: The objective of this project was to evaluate the factors that contribute to LGBTQIA2+ patient comfortability. This information was then used to understand how best to create a comfortable space for LGBTQIA2+ patients. METHODS/STUDY POPULATION: This survey was focused on underinsured and uninsured patients seen at the Rainbow Clinic - a free student-run LGBTQIA2+ clinic. Surveys were distributed by undergraduate volunteers on tablets as a qualtrics survey. Surveys collected demographic information in addition to 5 questions that assessed patient comfortability. These questions included evaluating the patient’s comfort with sharing information with the provider and the patient’s comfort of coming into clinical spaces. These surveys were distributed before and after clinic appointments to capture any changes in comfortability that could have occurred as a result of the appointment. RESULTS/ANTICIPATED RESULTS: Up to May of 2023, 49 patients were seen in Rainbow Clinic. 33 patients filled out the intake survey and 31 patients filled out the check-out survey resulting in a 67% and 63% response rate respectively. Questions were asked on a likert scale (1-5) from Strongly Disagree to Strongly Agree. Questions evaluating patient comfort in sharing information with their provider yielded an average score that was statistically significant, suggesting patients felt comfortable at the Rainbow Clinic. Additionally, patients indicated that the LGBTQIA2+ specific labeling of the Rainbow Clinic made them significantly more comfortable coming into the clinic. DISCUSSION/SIGNIFICANCE: This project suggests that patient comfortability can be improved by training and intentional LGBTQIA2+ labeling. Considering the hesitancy of this community towards healthcare, improving comfortability not only benefits clinical care and outcomes but can also bolster the body of research on this community.

OBJECTIVES/GOALS: Atopic dermatitis is one of the most common chronic childhood conditions worldwide and is associated with poor mental health outcomes. Our aim is to determine whether childhood atopic dermatitis is associated with symptoms of depression throughout childhood and adolescence, and whether this association is mediated by serum inflammatory markers. METHODS/STUDY POPULATION: We will perform a longitudinal analysis of over 7000 children from an existing prospective cohort. The primary exposure is atopic dermatitis (AD) annual period prevalence measured by a standardized questionnaire at 12 time points between age 6 months and 16 years. Depression is measured using self-reported responses to the Short Moods and Feelings Questionnaire at 6 time points between 10 and 18 years of age. Cross-sectional regression analyses will be performed to compare depressive signs between children with and without AD and test for dose-response effects with AD and depression. Longitudinal analyses will be conducted using mixed-effects models to estimate the average effect across childhood. We will complete a mediation analysis to determine the extent to which IL-6 and CRP mediate this association. RESULTS/ANTICIPATED RESULTS: We anticipate that atopic dermatitis will be associated with SMFQ scores in a dose response relationship, and that inflammatory markers CRP and IL-6 will partly mediate this association. DISCUSSION/SIGNIFICANCE OF IMPACT: Childhood is a critical time for mental health. Understanding the longitudinal relationship between atopic dermatitis, depression, and inflammatory mediators is crucial as new biologic treatments targeting inflammatory cascades are approved for atopic dermatitis and have the potential to prevent mental health conditions.

OBJECTIVES/GOALS: A workflow management tool is essential in order to help support consistent processes with transparency in next steps of the study process. Prior to this tool, staff has relied upon extensive training and coaching on the study process. While resources and guidelines exist, it requires additional time for staff to identify these resources and allows for confusion and rework. Implementation of a systematic workflow management tool was identified as a critical need in order to support streamlined processes, improve transparency and support business continuity, and to accelerate the study process. METHODS/STUDY POPULATION: This effort was undertaken as part of the Protocol Lifecycle Management effort to implement a comprehensive clinical trial management system for clinical research studies. Mayo Clinic has designed a workflow management tool within the Velos eResearch system. The workflow manager is dynamic and will present specific activities based on the study design and responses to data entered on the ad hoc forms. A Workflow Build group contributed to the design of the workflow in order to reflect appropriate, current operational processes. The workflow was vetted and validated with research teams. In addition to designing activities, planned dates and target timelines were established for relevant workflows to help promote transparency in the study start-up timelines and allow study staff to identify overdue activities. Study status controls were designed in the workflow to protect study staff from inadvertently changing the status until appropriate activities are complete. RESULTS/ANTICIPATED RESULTS: A dynamic workflow has been designed and implemented in the Velos eResearch system to support Mayo Clinic research sites. This system will be implemented February 24, 2020 to all consenting studies. DISCUSSION/SIGNIFICANCE OF IMPACT: The implementation of this workflow management tool is critical to help support research operations in a large, academic medical center. Benefits to implementation are expected to include improved transparency in the study status and next steps, reductions in rework due to confusion in next steps, better understanding from new staff in the appropriate study process, and improved timelines for study start-up. As we prepare for the implementation of the Velos eResearch system at Mayo Clinic, the workflow management tool has been identified in training sessions as a positive benefit.