OBJECTIVES/GOALS: This study aimed to investigate the mechanistic effects of fish oil (âμ-3 fatty acids) or evening primrose oil (âμ-6 fatty acids) supplementation on platelet reactivity in postmenopausal women. METHODS/STUDY POPULATION: Postmenopausal women were recruited from the Ann Arbor community and the University of Michigan Medicine Center. All subjects were recruited under study protocols approved by the University of Michigan IRB between November 2015 and March 2017. We conducted a randomized, double-blind, two-period crossover trial, consisting of a 60-day supplementation period followed by a 14-day washout period in between and at the end of the study. Subjects were treated daily in random order with 2g of fish oil supplement and 2g of evening primrose oil. Blood was drawn at baseline, post-supplementation, and after washout. The effects of fatty acid supplementation on platelet aggregation, dense granule secretion and activation of basal integrin âºIIbÎ23 were assessed following supplementation and washout period. RESULTS/ANTICIPATED RESULTS: The study started with 90 postmenopausal women. A total of 78 subjects completed the study, with 12 subjects dropping out due to non-compliance and medical reasons. Supplementation with fish oil attenuated the thrombin receptor PAR4-induced platelet aggregation, whereas primrose oil supplementation attenuated aggregation mediated by PAR4 or collagen. Supplementation with âμ-3 or âμ-6 fatty acids decreased platelet dense granule secretion and attenuated basal levels of integrin âºIIbÎ23 activation. Post-washout following supplementation with primrose oil, the thrombin receptor PAR1-induced platelet aggregation was similarly attenuated. For either treatment, the observed effects post supplementation on dense granule secretion and basal integrin activation were sustained after the washout. DISCUSSION/SIGNIFICANCE: Postmenopausal women are at increased risk for a cardiovascular event due to platelet hyperactivity. This study indicates that supplementation with âμ-3 and âμ-6 fatty acids may offer significant protection for postmenopausal women against cardiovascular diseases and occlusive thrombotic events by reducing platelet reactivity.

OBJECTIVES/SPECIFIC AIMS: (1) Evaluate safety of a novel influenza vaccination strategy in patients with plasma cell disorders. (2) Measure laboratory-confirmed influenza infection rates following a novel influenza vaccination strategy in patients with plasma cell disorders. (3) Evaluate clinical correlates of response following a novel influenza vaccination strategy in patients with plasma cell disorders. METHODS/STUDY POPULATION: We conducted a double-blind, randomized study over the 2015–16 flu season, comparing 2 doses of Fluzone® High-Dose influenza vaccination (separated by 30 d) to the current standard of care influenza vaccination. Patients were allocated to the experimental arm in 2:1 ratio compared with standard of care arm. Standard of care influenza vaccination was considered single age-based vaccination (standard dose for those <65 y and high dosefor those ≥65 y) and patients in this arm received a saline placebo injection at 30 days to assist in blinding. Eligibility criteria allowed any patient with a PCD and no contraindication to trivalent inactivated influenza vaccine. The primary endpoint was laboratory-confirmed flu infection rate. Protocol-driven surveillance screened patients for flu-like illnesses and performed laboratory testing for influenza until the end of the flu season in May 2016. Secondary endpoints include HAI titer serologic response rates, clinical correlates of protection from influenza infection, and exploratory studies of cell-mediated immunity through characterization of T cell subpopulations, cytokine profiles, and flu-specific T-cell responsiveness. RESULTS/ANTICIPATED RESULTS: In total, 122 plasma cell disorder patients were enrolled (97 with disease requiring therapy and 25 with asymptomatic gammopathy). Of those 48 patients received a single standard of care influenza vaccination and 74 patients received 2 doses of Fluzone® high-dose vaccine. Median age was 67 years (range 42–90). This 2-dose vaccination strategy was safely tolerated in all patients with no grade 2 adverse events attributed to vaccine. With close clinical follow-up, only 4% of patients receiving 2 vaccine doses developed laboratory confirmed influenza Versus 8.3% of those receiving single vaccine. When compared to the expected CDC influenza infection rate of 10%–15%, 1 sample, 2-tailed binomial testing revealed patients receiving 2 vaccines experienced a significantly lower rate of infection than the expected rate (p<0.05) whereas those receiving single vaccine showed no significant difference (p=0.38). DISCUSSION/SIGNIFICANCE OF IMPACT: This randomized study demonstrates that the 2 dose strategy of Fluzone® high-dose influenza vaccine is safely tolerated in patients with plasma cell disorders and associated with significantly less than expected laboratory-confirmed influenza infections. The results suggest that this novel vaccination strategy may have a clinical benefit in reducing influenza infections in plasma cell disorder patients and thus may have practice changing implications. Final analyses of serologic responses, clinical correlates of response, and cell-mediated immune correlates may provide valuable insights into in vivo “immune-competence” in patients with plasma cell disorders.

ABSTRACT IMPACT: This study establishes the association between childhood hypertension and health outcomes in early adulthood, identifying the need to understand blood pressure during early life for primary prevention of hypertension and cardiovascular disease. OBJECTIVES/GOALS: There is evidence that blood pressure level in early life can influence hypertension and other cardiovascular risk factors later in life. We examined whether hypertension before the age of 18 is associated with higher odds of obesity and hypertension after the age of 18. METHODS/STUDY POPULATION: We studied 19,367 children and adolescents from the Vanderbilt University Medical Center’s Synthetic Derivative, a de-identified version of the electronic medical record. Childhood hypertension was defined as systolic blood pressure (SBP) ≥130 mmHg or diastolic blood pressure (DBP) ≥80 mmHg at three or more outpatient visits before the age of 18. Obesity and hypertension in early adulthood were the primary outcomes. Obesity was defined as being above normal weight for adulthood height at age 30 based on the NIH’s body mass index tables. Hypertension was defined as SBP ≥130 mmHg or DBP ≥80 mmHg at three or more outpatient visits after the age of 18. Odds ratios and 95% confidence intervals (CIs) were computed from logistic regression models adjusted for demographics, medication use, and childhood weight. RESULTS/ANTICIPATED RESULTS: Most subjects were female (63%) and white (80%). During childhood, 17% of participants had hypertension. Approximately 58% of this group were obese at age 30, and 38% had hypertension as adults. Compared to females with no childhood hypertension, females with childhood hypertension had 1.35 times higher odds of being obese at age 30 (95% CI: 1.15, 1.58) and 3.56 times higher odds of having hypertension over the age of 18 (95% CI: 3.09, 4.09). Males with childhood hypertension, compared to males without, had 1.28 times higher odds of being obese at age 30 (95% CI: 1.08, 1.52) and 2.74 times higher odds of having hypertension over the age of 18 (95% CI: 2.35, 3.20). Associations between childhood hypertension, early adulthood obesity, and hypertension significantly differed by gender (p-for-interaction for both: <0.01). DISCUSSION/SIGNIFICANCE OF FINDINGS: Childhood hypertension is associated with obesity and hypertension in early adulthood. Understanding blood pressure levels in childhood and adolescence may help target efforts to reduce early adulthood cardiovascular risk factors.

OBJECTIVES/GOALS: Preterm birth is the most common birth complication in the United States. To date, there are no effective public health strategies to reduce the burden of prematurity. Using geospatial information system (GIS) mapping, we identified the most salient risk factors of preterm birth across US counties targetable for future interventions. METHODS/STUDY POPULATION: Risk factors of preterm birth were identified from the perinatal health nonprofit organization, March of Dimes, and included factors such as obesity, smoking, insurance coverage and poverty. US 2013 county-level data on sociodemographic characteristics, behavioral risk factors and preterm birth were extracted and combined from the American Census, Center for Disease Control, and US Health Resources and Services Administration. Spatial autocorrelation and multivariate spatial regression were used to determine the risk factors most strongly associated with preterm birth. These models were adjusted for race, given well-documented race disparities for preterm birth. As a case-study comparison, we mapped risk factors in the two states with the highest and lowest proportion of preterm births in 2013. RESULTS/ANTICIPATED RESULTS: In our preliminary analysis, obesity was the factor most strongly associated with preterm birth (ß = 7.32, SE: 1.13, p<0.001) at the US county-level. Surprisingly, smoking was not found to be significantly associated with preterm birth. In 2013, Vermont had the lowest prevalence of preterm birth at 7.6% and Mississippi had the highest prevalence of preterm birth at 13.1%. Health insurance coverage and obesity were the two risk factors that differed between Vermont and Mississippi. The median proportion of uninsured individuals in Mississippi counties was four times higher than that of Vermont counties (26.3% vs 10.9%, p<0.01). Similarly, the median obesity prevalence in Mississippi counties was significantly higher than the median obesity prevalence in Vermont counties (38.8% vs. 25.2%). DISCUSSION/SIGNIFICANCE OF IMPACT: Public health efforts aimed at reducing obesity and increasing health insurance coverage may have the greatest impact at addressing the US burden of preterm birth. Further, geospatial mapping is a powerful analytic tool to identify regions in the US where preterm birth interventions would be most beneficial.

OBJECTIVES/SPECIFIC AIMS: Our objective was to compare the proteomics of HDL between youth with T1DM and healthy controls (HC). METHODS/STUDY POPULATION: We did chromatography-based HDL purification and SWATH-MS-based proteomic quantitation. Proteomic alterations of HDL fractions and their association with glycemic control was examined. Study population: 26 patients with T1DM and 13 HC. RESULTS/ANTICIPATED RESULTS: We quantified 78 proteins in isolated HDL, using mass spectrometry and label-free SWATH quantification. Youth with T1DM had significantly higher protein levels of A1BG (P = 0.008), A2AP (P = 0.0448), APOA4 (P = 0.0366), CFAH (P = 0.0476), FHR2 (P = 0.0005), ITIH4(P = 0.01), PGRP2 (P = 0.0167) and lower levels of ALBU (P = 0.0164) and CO3 (P = 0.019) compared to HC. A1BG (r=0.541, P<0.001) and ITIH4 (r=0.357, P = 0.026) were significantly positively correlated with HbA1c. DISCUSSION/SIGNIFICANCE OF IMPACT: Youth with T1DM have proteomic alterations of their HDL compared to HC, despite similar concentration of HDL cholesterol, that might affect the cardioprotective mechanisms of HDL. Future efforts should focus on investigating the role of these HDL associated proteins in regard to HDL function and their role in CVD risk in patients with T1DM.

OBJECTIVES/SPECIFIC AIMS: A hallmark of progressive HIV-1 infection is the massive activation and depletion of the gut barrier protective CD4 T helper subsets (Th17 and Th22) in the intestinal mucosa. The loss of these cells is thought to contribute to microbial translocation and systemic immune activation that occurs during chronic infection. In addition to the loss of protective Th subsets, we previously showed that chronically HIV-1 infected individuals have an altered colonic mucosal microbiome, which is in part characterized by a lower relative abundance of bacteria that produce the short-chain fatty acid butyrate in conjunction with increased relative abundance of gram-negative pathobionts. This dysbiosis was linked to markers of mucosal and systemic immune activation in these individuals. Following up on these clinical observations, we sought to understand how a loss of butyrate might contribute to HIV-associated inflammation. Initial studies showed that the addition of butyrate to cultured lamina propria mononuclear cells (LPMC) resulted in decreased pathobiont-driven gut T cell activation, HIV-1 infection levels and production of IL-17 and IFNy. Since the gut barrier protective Th17 and Th22 subsets are preferentially infected and depleted, which is critical to HIV-1 pathogenesis, we wanted to determine the mechanism by which butyrate modulates activation of these important Th subsets in the gut. METHODS/STUDY POPULATION: Total LPMCs or purified LP CD4 T cells were isolated from human jejunal tissue (n=3–6), labeled with CFSE and cultured with TCR/CD28 beads to mimic APC driven T cell activation, with the addition of butyrate at physiologic doses(0–2 mM). Four days after culture, secreted cytokine(IL-17 and IFNy) levels were measured by ELISA. Cells were then short-term (4 hr) mitogenically stimulated (PMA/Ionomycin) in the presence of a golgi transport inhibitor. Total CD4 T cell activation (CD38+/HLA-DR+, CD25+), proliferation (CFSElow), and frequencies of intracellular cytokines were measured by multi-color flow cytometry. Paired t-tests were performed to determine statistical significance. RESULTS/ANTICIPATED RESULTS: Butyrate inhibited LP CD4 T cell activation (p=0.013) and proliferation (p=0.015) within total LPMCs stimulated with TCR/CD28 beads in a dose-dependent manner, with significant activity starting at 0.125 mM. Quantification of total secreted cytokines revealed that butyrate significantly decreased both IL-17 and IFNy production after 4 days of culture at 0.0625 mM and 0.25 mM of butyrate, respectively. Assays using purified LP CD4 T cells demonstrated that butyrate directly decreased LP CD4 T cell activation, proliferation and cytokine production in response to TCR/CD28 stimulation. Studies on specific T helper subsets revealed that butyrate inhibited proliferation of Th17 cells at lower concentrations (IC50:0.147 mM) compared with Th1 (IC50:0.229 mM) and Th22 (IC50:0.258 mM) and Th non-IL-22/IL-17/IFNy producing (IC50:2.14 mM) subsets. In addition, it appeared there was a paradoxical increase of HIV-1 infection levels at lower concentrations of butyrate (0.125 mM). DISCUSSION/SIGNIFICANCE OF IMPACT: The addition of butyrate to activated LP CD4 T cells decreases TCR-mediated activation in a dose-dependent manner, and butyrate acts directly on purified LP CD4 T cell populations independent of other cell populations. Butyrate differentially inhibited the proliferation of Th17, Th1, and Th22 subsets, with Th17 cells being the most sensitive to butyrate but increased the infection levels of all T helper subsets at low concentrations. Further studies are needed to determine the mechanism of butyrate’s actions on LP Th cells and the sensitivity of Th17 cells to the inhibitory effects of butyrate. These results could help direct targeted manipulation of the colonic microbiome of HIV-1 infected individuals to help resolve inflammation and limit the impact of the infection in the gut mucosa and systemically.

The ability of research networks and individual institutions to effectively and efficiently prepare, respond, and adapt to emergent challenges is essential for the biomedical research enterprise. At the beginning of 2021, a special Working Group was formed by individuals in the Clinical and Translational Science Award (CTSA) consortium and approved by the CTSA Steering Committee to explore “Adaptive Capacity and Preparedness (AC&P) of CTSA Hubs.” The AC&P Working Group took a pragmatic Environmental Scan (E-Scan) approach of utilizing the diverse data that had been collected through existing mechanisms. The Local Adaptive Capacity framework was adapted to illustrate the interconnectedness of CTSA programs and services, while exposing how the demands of the pandemic forced them to quickly pivot and adapt. This paper presents a synopsis of the themes and lessons learned that emerged from individual sections of the E-Scan. Lessons learned from this study may improve our understanding of adaptive capacity and preparedness at different levels, as well as help strengthen the core service models, strategies, and foster innovation in clinical and translational science research.

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: 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/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: 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.

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/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: 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: 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.