OBJECTIVES/SPECIFIC AIMS: Chronically elevated cytokines from un-abating low-grade inflammation in heart failure (HF) results in Protein-Energy Malnutrition (PEM). However, the impact of PEM on clinical outcomes of admissions for HF exacerbations has not been evaluated in a national data. METHODS/STUDY POPULATION: From the 2012-2014 Nationwide Inpatient Sample (NIS) patient’s discharge records for primary HF admissions, we identified patients with concomitant PEM, and their demographic and comorbid factors. We propensity-matched PEM cohorts (32,771) to no-PEM controls (1:1) using a greedy algorithm-based methodology and estimated the effect of different clinical outcomes (SAS 9.4). RESULTS/ANTICIPATED RESULTS: There were 32,771 (~163,885) cases of PEM among the 541,679 (~2,708,395) primary admissions for HF between 2012 and 2014 in the US. PEM cases were older (PEM:76 vs. no-PEM:72 years), Whites (70.75% vs. 67.30%), and had higher comorbid burden, with Deyo-comorbidity index >3 (31.61% vs. 26.30%). However, PEM cases had lower rates of obesity, hyperlipidemia and diabetes. After propensity-matching, PEM was associated with higher mortality (AOR:2.48[2.31-2.66]), cardiogenic shock (3.11[2.79-3.46]), cardiac arrest (2.30[1.96-2.70]), acute kidney failure (1.49[1.44-1.54]), acute respiratory failure (1.57[1.51-1.64]), mechanical ventilation (2.72[2.50-2.97]). PEM also resulted in higher non-routine discharges (2.24[2.17-2.31]), hospital cost ($80,534[78,496-82,625] vs. $43,226[42,376-44,093]) and longer duration of admission (8.61[8.49-8.74] vs. 5.28[5.23-5.34] days). DISCUSSION/SIGNIFICANCE OF IMPACT: In the US, PEM is a common comorbidity among hospitalized HF subjects, and results in devastating health outcomes. Early identification and prevention of PEM in heart failure subjects during clinic visits and prompt treatment of PEM both in the clinic and during hospitalization are essential to decrease the excess burden of PEM.

OBJECTIVES/SPECIFIC AIMS: -This study aims to evaluate our retention rate into our prospective clinical trial. We will be comparing the rate of withdrawal both before and after our revamped informed consent process. -We aim to assess patient satisfaction with our study and u METHODS/STUDY POPULATION: -The informed consent process for an observational prospective study at our institution has been modified to lengthen the recruitment and consenting process. -In brief, the research protocol for this observational prospective aims to evaluate the role of steroids on ulcer healing in patients with ulcerative colitis. This study involves an initial standard of care colonoscopy with biopsies and photos. The areas biopsied are marked with a tattoo. The patients are started on steroids for management of their Ulcerative Colitis, and must return for two research colonoscopies at one week post- initial diagnostic visit, and at one month. Additional study biopsies are obtained at the one week visit and photo documentation is obtained. At the one month visit, only photos are obtained to document healing. -In addition to patients with active ulcerative colitis, this study recruits control groups of patients with UC in remission, as well as two groups of normal control patients (one group on steroids for non-IBD reasons, and one group not on steroids. -Prior to our informed consent intervention, patients were screened for eligibility on the day of their standard of care endoscopy. The study was explained to the patient prior to their endoscopy, often in the “pre-op” endoscopy suite. -Our intervention seeks to draw out the consent and recruitment process. All patients scheduled for upcoming endoscopies will be mailed a generic flyer announcing research studies occurring in the endoscopy suite. Patients will be pre-screened at least a week prior to endoscopy with the aid of the endoscopy scheduler. Patients interested in hearing about research will be contacted via phone by study personnel, and a copy of the consent as well as a brief summary will be mailed to the patient. -Patients potentially interested in study participation will be asked to arrive 30 minutes earlier than they typically would for their procedure, and they will be consented in a quiet and private consultation room. They will be given ample time to ask clarifying questions regarding the study. -At the conclusion of their participation, patients will receive an anonymous post-participation survey that seeks to assess their feelings regarding the study and their understanding of the research process. RESULTS/ANTICIPATED RESULTS: DISCUSSION/SIGNIFICANCE OF IMPACT: This study adds to the ongoing body of evidence suggesting that the informed consent process is more than the three key elements initially described by the Belmont Report 40 years ago. Several factors can impact patient’s willingness to participate in research, and the amount of time it takes for patients to achieve all three elements of consent can vary from person to person. The traditional method of consent just prior to study entrance is one that needs to be revisited, and we propose that prolonging the consenting process will positively impact not only patients, but also the overall research process by ensuring that those who decide to participate remain adherent to study protocols.

OBJECTIVES/GOALS: We conducted a randomized field trail to evaluate the efficacy and safety of a novel vector control strategy that involves treating urban backyard chickens with ivermectin (IVM), a widely used antiparasitic and mosquitocial drug. The goal was to reduce vector mosquito populations and West Nile virus (WNV) transmission. METHODS/STUDY POPULATION: We placed eight flocks—four treated and four untreated control—of six Lohmann brown chickens (16 month-old) each in backyard coops across Davis, CA and administered IVM in feed daily at treated coops (200 mg IVM/kg feed) for eleven weeks. We monitored entomological indices weekly (i.e. mosquito abundance, WNV infection prevalence, and parity rate) in Culex mosquito populations near (10 m) and far (150 m) from each coop location for the peak WNV transmission season (Jul-Sep 2019). We also monitored serum IVM levels in treated chickens and tested for WNV antibodies in all chickens throughout the study. RESULTS/ANTICIPATED RESULTS: Since IVM impacts only mosquitoes that live long enough to take a bloodmeal from a treated chicken, we do not expect to find a marked difference in adult Culex abundance between the two treatment arms, but we expect to find a reduction in WNV infection prevalence and a shift in female mosquito age structure towards younger, uninfected individuals at treated coops. We also anticipate seroconversions in treated chickens to occur at lower rates versus untreated control chickens indicating a reduction in WNV transmission intensity at treated coops. We observed no negative health outcomes from the long-term ingestion of IVM by study chickens. A pathological investigation is underway to compare histological findings between treated and untreated chickens. DISCUSSION/SIGNIFICANCE OF IMPACT: IVM provides the potential for targeted mosquito control. Reduced WNV transmission dynamics here is a stepping stone to a commercial WNV control strategy; IVM-treated feed for wild birds for homeowners’ use to combat WNV transmission in their neighborhoods.

OBJECTIVES/SPECIFIC AIMS: The goal of this study was to determine the impact of an RN-guided preoperative educational intervention in a minimally invasive gynecologic oncology surgery cohort. Our specific objectives include: 1. To assess the impact of preoperative education on quality outcomes such as length of stay and discharge by noon rates. 2. To characterize the differential burden of post-operative communications on nursing staff in patients who received education versus those who did not. METHODS/STUDY POPULATION: This was a retrospective cohort study. We identified thirteen gynecologic oncology patients scheduled for minimally invasive surgeries (laparoscopic and robot-assisted) between March 2017 and July 2017. These patients served as the pilot for a quality improvement project comprised of a preoperative teaching session by a gynecologic oncology registered nurse (RN). Patients also received an educational booklet, designed by gynecologic oncology care team members including nurses and physicians. Educational topics included expectations for pre-, intra-, and post-operation; guidelines for post-op care at home, important contact information, and postoperative medication instructions. Patients were also given a prescription for their post-operative medications and asked to fill them before their surgeries. Following their surgeries, patients were asked to take a voluntary and anonymous 8-item online survey assessing their satisfaction with the educational intervention, their procedure, and their hospital stay. We matched these patients in a one-to-two ratio, to patients not included in the pilot, on the basis of surgery type and age. All subjects and controls spoke English as their primary language. We abstracted data from the electronic medical record including pathologic diagnosis, number of postoperative communications (telephone and email), content of postoperative communications, and various clinical characteristics. Outcome measures include length-of-stay, discharge-by-noon rate, percentage of patients with postoperative questions, and number of postoperative concerns communicated via telephone or email. RESULTS/ANTICIPATED RESULTS: There were 39 patients in the final cohort; thirteen of whom who participated in the pilot project, POET (Perioperative Educational Tool). Thirty-nine percent of POET patients had questions regarding their surgery or post-op care as compared with 61.5% of controls (P = 0.087). Nineteen percent of controls had questions about their postoperative medications, compared with zero percent of POET patients (P = 0.046). POET patients had an average of 0.69 postoperative communications, compared with 1.12 in controls. The length of stay was 8 hours in POET patients and 26 hours in controls (P = 0.317). The discharge before noon rate was 20% in POET patients and 25% in controls (P = 0.41). Of the 10 POET patients who completed the anonymous online survey, 100% liked the approach to teaching; 100% felt that they received consistent information regarding surgery, hospital stay, and post-op care, 100% felt prepared at discharge, 100% picked up their postoperative medications without difficulty prior to surgery. DISCUSSION/SIGNIFICANCE OF IMPACT: Patients uniformly had a positive response to their preoperative education. Although our primary outcomes were not statistically significant, the results of this unpowered, observational study suggest that anticipatory education such as we provided, may decrease the burden of post-operative communications related to surgical expectations. A preoperative teaching intervention may be especially valuable in educating patients about their postoperative medications. Although POET patients had significantly fewer questions about their postoperative medications, refilling their medications before their procedures did not seem to have an effect on discharge-by-noon rates. This may demonstrate that delays in disposition are not influenced by post-operative prescriptions. One limitation of our study is that we did not prospectively measure patient satisfaction with surgical care. Another limitation is that the pilot educational intervention was conducted entirely in English. To our knowledge, there exists no analysis of the effect of English language proficiency on outcomes such as patient satisfaction, length of stay, and discharge-by-noon rates, and other clinical outcomes in this surgical patient population. It is well-demonstrated in the literature that limited English proficiency contributes negatively to health care quality. Our next steps involve establishing a prospective study to measure the effects of preoperative education on patient satisfaction with their procedure, post-operative communications, and discharge by noon rates. We also plan to administer POET to Spanish- and Chinese-language speakers, to better understand the effect of limited English proficiency on our outcome measures of interest.

OBJECTIVES/GOALS: Poor housing conditions and quality can be linked with residents’environmental exposures, which may contribute to a variety of adverse health outcomes. This systematic literature review will examine literature around housing, environmental exposure, and health; and policy implications to reduce the impact of housing on environmental exposures. METHODS/STUDY POPULATION: This systematic literature review will identify and evaluate published peer-reviewed articles as well as governmental and NGO policy briefs relating to connections between housing quality and condition, neighborhood characteristics, and environmental exposures (e.g., lead poisoning, secondhand smoke, PFAS chemicals) in the United States; and will particularly focus on health implications of such environmental exposures, racial/ethnic and socioeconomic disparities in exposure, and current and future policy recommendations to alleviate the association between housing and environmental risk. A computerized literature search of relevant electronic databases (e.g., PubMed, Sociological Abstracts, EPA database, Congressional database) for literature published after 2000 will be conducted. RESULTS/ANTICIPATED RESULTS: The findings from this literature review will be split up into categorizations around (1) the contribution of housing/neighborhoods on resident environmental exposure; (2) geospatial and demographic inequality (historic and current) around housing/neighborhood conditions contributing to disproportionate environmental exposures for low-income and minoritized residents; (3) health implications of environmental exposures; (4) prior policy addressing the connections between housing/neighborhoods and environmental risk; and (5) future policy recommendations to improve housing/neighborhood quality and minimize environmental exposures for residents. DISCUSSION/SIGNIFICANCE: This project will illuminate connections between housing conditions and environmental exposures, health implications of these exposures, and contribute to advancing understanding of potential policies to reduce adverse environmental health impacts of poor housing conditions for residents (particularly for low-income, minoritized groups).

ABSTRACT IMPACT: To improve care and services for patients with chronic disease, health systems are focusing on evaluating social determinants of health of populations at risk; this information is currently not available in electronic health records (EHR) but we show that it could be accessed by linking area deprivation index to EHR. OBJECTIVES/GOALS: To inform care delivery and policy, health care systems are studying ways of improving social determinants of health (SDoH) in patients with chronic disease such as diabetes (DM). Our goal was to better characterize the SDoH of a cohort of DM patients by using the area deprivation index (ADI). METHODS/STUDY POPULATION: Our study population included DM patients seen in primary care practices in 2013-2017. We integrated ADI levels to data extracted from electronic health records (EHR). ADI ranks neighborhoods by socioeconomic status calculated from income, education, employment and housing quality. ADI has 10 levels that we grouped into 5 categories of 2 levels. Addresses were geocoded using ArcMap to obtain census block groups information. We used multivariable logistic regression to calculate odds ratios (OR) and 95% confidence intervals [], with diabetic complications as a binary dependent variable, ADI levels as the exposure, and demographics, smoking status and number of comorbidities as confounders. RESULTS/ANTICIPATED RESULTS: Our study population included 8,558 patients: 56% were female, 61% white, 31% black, 28% were on Medicare, 66% on commercial insurance, median age was 55 years, 57% never smoked, 10% had no comorbidities, 42% had 3 or more comorbidities, and 37% developed diabetic-related complications. After evaluating collinearity and adjusting for confounders, our multivariable analysis showed that worsening ADI was associated with higher likelihood of complications. Compared to ADI level 1&2 (least disadvantaged), the ORs for patients residing in neighborhoods with ADI levels 3&4, 5&6, 7&8, 9&10 (most disadvantaged) were respectively 1.01 [0.88-1.16), 1.20 [1.04-1.39], 1.15 [0.99-1.33], 1.30 [1.11-1.52]. DISCUSSION/SIGNIFICANCE OF FINDINGS: Neighborhood ADI could provide precious information to health care providers when associated to the EHR. We found that neighborhoods with ADI level 9&10, which is not collected in the EHR, was significantly associated with a higher burden of disease. ADI could serve as a proxy for evaluating SDoH.

OBJECTIVES/SPECIFIC AIMS: Protein Energy Malnutrition (PEM) could compromise the body’s defense systems resulting in sepsis, which further depletes calorie stores. Among hospitalized patients, we investigate 1) the relationship between PEM and sepsis, 2) the impact of PEM on trends in mortality from sepsis, and 3) the influence of PEM on clinical outcomes of sepsis. METHODS/STUDY POPULATION: Using the 2014 Healthcare Cost and Utilization Project - Nationwide Inpatient Sample (NIS) patient’s discharge records, we identified patients with sepsis, PEM, and other clinical conditions with ICD-9-CM codes. After stratifying sepsis into two: uncomplicated (without shock) and complicated (with shock), we estimated the adjusted odds (aOR) of developing sepsis (total, uncomplicated and complicated) with PEM. Then, we selected hospitalizations with sepsis from 2007-2014 years of the HCUP-NIS, and calculated the trend in mortality from sepsis, stratified by PEM status, as an effect modifier. Finally, we matched PEM to no PEM (1:1) using a greedy algorithm-based propensity methodology and estimated the effect of having mortality, complicated sepsis and 10 other clinical outcomes and healthcare utilization (SAS 9.4). RESULTS/ANTICIPATED RESULTS: PEM was associated with higher odds for sepsis (aOR:3.97[3.89-4.05]), and complicated vs. uncomplicated sepsis (1.74[1.67-1.81]). Although mortality in sepsis has been trending down from 2007-2014 (−1.19%/year, p-trend<0.0001), the decrease was less pronounced among those with PEM vs. no-PEM (−0.86%/year vs. −1.29%/year, p-value < 0.0001). After propensity matching, PEM was associated with higher mortality (1.35[1.32-1.37]), cost ($160,724[159,517-161,940] vs. $86,650[85,931-87,375]), length of stay (14.76[14.68-14.84] vs. 8.49[8.45-8.56] days), and worse outcomes in general. DISCUSSION/SIGNIFICANCE OF IMPACT: PEM is a risk factor of sepsis and associated with poorer outcomes among septic patients. A concerted effort involving primary care physicians, nutritionists, nurses in identifying, preventing, and treatment of PEM in the community-dwelling individuals before hospitalization might mitigate against these devastating outcomes.

OBJECTIVES/GOALS: This investigation aimed to develop and validate a subject-specific finite element analysis (FEA) model with subject-specific mechanical loads during walking and to use this method to compare mechanical stresses between transfemoral and transtibial osseointegrated (OI) implants. METHODS/STUDY POPULATION: One patient with a unilateral transtibial OI prosthesis and one with a unilateral transfemoral OI prosthesis participated in motion analysis to collect kinematics and ground reaction forces during overground walking. Subject-specific musculoskeletal models were created, and static optimization was used to estimate muscle and joint reaction forces throughout walking. 3D FEA models of the tibia, femur, and implants were created using ScanIP and exported into ABAQUS CAE. Muscle forces were applied at corresponding origin/insertion locations, determined from the musculoskeletal models [7]. Fixed boundary conditions were applied at proximal joint centers, and bone stresses throughout gait were calculated. OpenSim and FEA derived estimates of joint reaction forces were compared for validation. RESULTS/ANTICIPATED RESULTS: A maximum stress of 65.53 MPa and 60.70 MPa was observed at the bone-implant interface for the transtibial and transfemoral patients (respectively) in the late stance phase of the walking task, corresponding to terminal stance and heel off. Averaged root mean squared errors of the walking task (in the anterior-posterior, inferior-superior, and medial-lateral directions, respectively) for the transtibial and transfemoral patients were (124, 152, 80) N, (71, 80, 30) N, and (190, 62, 30) N, respectively. DISCUSSION/SIGNIFICANCE: The purpose of the above study was to develop a methodology for determining subject-specific mechanical loads during walking using finite element analysis and compare mechanical stresses in patients with transfemoral and transtibial OI. Similar stresses between the two implant types were found.

OBJECTIVES/GOALS: To apply implementation science strategies to evaluate the impact of the 2016 Pennsylvania (PA) Medicaid payment policy change on hospital-level access to immediate postpartum long-acting reversible contraception (IPP LARC), an evidence-based strategy to increase contraceptive access; to identify differences by rurality and academic status. METHODS/STUDY POPULATION: We conducted a web-based, IRB-exempt survey of Labor and Delivery (L&D) leaders at all PA hospitals in Summer-Fall 2022, assessing hospital characteristics, contraceptive practices, and facilitators/barriers to IPP LARC implementation, using concepts from health services studies of small subsets of implementing hospitals; we translate these concepts into policy evaluation by sampling the complete population of Pennsylvania hospitals with active L&D units. L&D hospitals were characterized as sustainers if they implemented by 2019 and continued to provide IPP LARC, as implementers if they implemented IPP LARC in 2020-22, and non-implementers if they had not started the process. We use the Center for Rural Pennsylvania definition of rural: counties with RESULTS/ANTICIPATED RESULTS: We collected data from 48/74 (64.9%) hospitals with L&D units. Hospitals were heterogenous with 18/48 (37.5%) in rural counties and 15/48 (31.3%) identifying as academic. A minority of hospitals provide IPP LARC, with 17/48 (35.4%) offering implants and 16/48 (33.3%) offering intrauterine devices (IUD) immediately postpartum. Before the PA Medicaid payment policy change, few offered implants [4/48 (8.3%)] or IUDs [1/48 (2.1%)]. Non-rural hospitals implemented IPP LARC more often and on an earlier timeline than rural hospitals: [7/30 (23.3%) v 3/18 (16.7%)] sustainers, [5/30 (16.6%) v 2/18 (11.1%)] implementers. Common facilitators include clinical champions, meeting patient needs, and adequate knowledge. Planned analyses include implementation barriers, and impact of external implementation support. DISCUSSION/SIGNIFICANCE: Despite unmet need in rural populations for evidence-based contraception, rural hospitals were less likely to implement IPP LARC. Implementation support should be designed to meet the needs of rural hospitals. Implementation science methods can be translated to evaluate the impact of healthcare policy on access to care.

ABSTRACT IMPACT: Current practice guidelines offer a variety of treatment options for sternal reconstruction but complications and infections remain a serious surgical problem. This work seeks to provide a comprehensive picture of the com-morbidities and reconstructive methods that lead to success and improve patient outcomes. OBJECTIVES/GOALS: Patients that undergo cardiac surgery via the median sternotomy approach are at risk of wound complications that require repair. We seek to evaluate how outcomes of sternal reconstruction are influenced by patient comorbidities, flap usage and internal mammary artery grafts and methods of sternal closure. METHODS/STUDY POPULATION: We identified patients between 2005 and 2020 who underwent sternotomy followed by debridement and flap coverage at our institution. Comorbidities, method of reconstruction, demographic data, surgical history, and other factors pertaining to mortality and morbidity were collected. The data will then be analyzed to identify population characteristics using logistic regression variables to determine univariate and adjusted multivariable measures of association with mortality. We present the pre-liminary data analyzed using chi-square and one-way anova in R. RESULTS/ANTICIPATED RESULTS: In this study we present a preliminary characterization of one institution’s sternal reconstruction patient outcomes with a variety of reconstruction methods including pectoralis advancement flaps, omental flaps and latissumus dorsi flaps. Notable preoperative comorbidities include 50% of patients > age 60, 18% with diabetes mellitus, 18 % with diagnosed hypertension, 18% with COPD, and 9% with a smoking history DISCUSSION/SIGNIFICANCE OF FINDINGS: In an evolving cardiothoracic landscape, clinical characteristics of patients being treated for sternal reconstructive surgery present a moving target. Understanding current risk factors, preoperative management and timing for aggressive surgical treatment offers an opportunity to update treatment protocol and maximize successful outcomes.

OBJECTIVES/GOALS: In 2016, more than 3,100 children died, and an estimated 17,000 children had non-fatal injuries, from firearms in the United States. In this study, we used hospital charges as a proxy for medical resource utilization, and compared differences in charges by intent of firearm injury among children. METHODS/STUDY POPULATION: In this cross-sectional study of the 2016 Nationwide Emergency Department Sample, we identified firearm injury cases among children aged 19 years or younger using ICD-10-CM external cause of morbidity codes. Injury intent was characterized as unintentional, assault, self-inflicted, undetermined, or due to legal intervention. We included patients treated and released from the emergency department (ED) or admitted alive to the hospital, and excluded those who were transferred or died in the ED. We used linear regressions with survey weighting to compare differences in mean healthcare charges by firearm injury intent, with and without adjustment for ED disposition. RESULTS/ANTICIPATED RESULTS: Among 12,469 cases in the weighted sample, mean age was 16.5 years, a majority were male (88.2%) and Medicaid-insured (57.8%), and 64% were discharged from the ED and 36% admitted. Injuries were 49.0% unintentional, 45.1% assault-related, and 1.8% self-inflicted. Compared to children with self-inflicted injuries (charges $115,224), children with assault-related injuries (charges $55,052; p<0.007) and unintentional injuries (charges $38,643; p<0.001) had lower mean charges per visit. Differences in charges were no longer significant after adjusting for ED disposition, as 85.8% of self-inflicted injuries were admitted, compared to 46.5% of assault-related and 24.3% of unintentional injuries. DISCUSSION/SIGNIFICANCE OF IMPACT: Although the majority of pediatric firearm-related injuries resulting in emergency department care are unintentional or assault-related, self-inflicted injuries result in greater per visit hospital charges, attributable to higher hospitalization rates, and likely due to more severe injuries.

OBJECTIVES/GOALS: Increases in anxiety and depression during adolescence may be related to increased biological reactivity to negative social feedback (i.e., social threat sensitivity). Our goal was to identify biomarkers of social threat sensitivity, which may provide unique etiological insight to inform early detection and intervention efforts. METHODS/STUDY POPULATION: Adolescents aged 12-14 (N=84; 55% female; 80% White; 69% annual family income <$70,000) were recruited. Youth viewed a series of happy, neutral, and angry faces while eye-tracking and electroencephalogram (EEG) data were recorded to capture cognitive and neural markers of sensitivity to social threat (i.e., an angry face). Fixation time and time to disengage from angry faces were derived from eye-tracking and event-related potentials were derived from EEG, which index rapid attention capture (P1), attention selection and discrimination (N170), and cognitive control (N2). Adolescents also completed a social stress task and provided salivary cortisol samples to assess endocrine reactivity. Social anxiety and depressive symptoms were self-reported concurrently and one year later. RESULTS/ANTICIPATED RESULTS: Latency to disengage from threatening faces was associated with lower N2 amplitudes (indexing poor cognitive control; r= -.24, p = .03) and higher concurrent social anxiety (r = .28, p = .01). Higher N170 amplitudes, reflecting attentional selection and discrimination in favor of threatening faces, predicted increases in depressive symptoms one year later (b= .88, p = .02). No other neurophysiological measures were associated with each other or with concurrent or prospective symptomatology. DISCUSSION/SIGNIFICANCE: Eye-tracking and EEG measures indexing difficulty disengaging from social threat and poor cognitive control may be biomarkers of social anxiety, which could be utilized as novel intervention targets. High N170 amplitudes to social threat, derived from EEG, may have clinical utility as a susceptibility/risk biomarker for depressive symptoms.

OBJECTIVES/GOALS: Cancer survivors are at increased risk for type 2 diabetes mellitus.It is not clear if diabetes susceptibility is due to shared risk factors for cancer and diabetes, such as obesity, or if it is directly related to cancer and its treatment. We investigated the association between malignancy and insulin resistance, a major risk factor for diabetes. METHODS/STUDY POPULATION: 20 adult patients with treated hematological malignancies and 21 controls without cancer were included in the study. Individuals with pre-existing diabetes were excluded. All patients underwent a 2-hour 75-gram oral glucose tolerance test (OGTT). Hyperinsulinemic-euglycemic clamps were performed to measure the steady-state glucose infusion rate (M-value) as an indicator of whole-body glucose utilization during insulin stimulation. Insulin sensitivity index was calculated by dividing M-value over the steady-state plasma insulin (M/I). RESULTS/ANTICIPATED RESULTS: Fasting or postprandial plasma glucose levels during the OGTT did not differ significantly between malignancy patients and controls (Table 2). Difference in the insulin-stimulated glucose utilization (M-value) was not statistically significant among cancer patients and controls (median, 7.2 [IQR, 6.2-10.4] vs. 7.3 [IQR, 5.5-8.9] mg/kg/min; P = 0.261). M/I index was significantly higher in malignancy patients compared to controls (median, 42.4 mg/kg/min/(µU/ml) [IQR, 33.9-67.2] vs. 23.4 mg/kg/min/(µU/ml) [IQR, 12.9-29.2], P <0.001), however insulin clearance was also lower in the controls. In multivariate analysis, only BMI was significantly associated with M-value (β = −0.2 (95% CI −0.4, −0.1), P = 0.004), and M/I (β = −2 (95% CI −3.4, −0.5), P = 0.009). DISCUSSION/SIGNIFICANCE OF IMPACT: Our data suggest that the major contributor to diabetes development after diagnosis of cancer in adults is obesity-induced insulin resistance, not malignancy related factors. These findings emphasize the importance of obesity management in long-term survival of cancer patients, as diabetes is a risk factor for mortality in this patient population.

OBJECTIVES/GOALS: Prematurity and perinatal brain injury are known risk factors for strabismus. In this study, we sought to understand the link between neonatal neuroimaging measures in very preterm infants and the emergence of strabismus later in life. Study findings may inform if neonatal brain MRI could serve as a prognostic tool for this visual disorder. METHODS/STUDY POPULATION: This study draws from a longitudinal cohort of very preterm infants (VPT, < 30 weeks gestation, range 23 – 29 weeks) who underwent an MRI scan at 36 to 43 weeks postmenstrual age (PMA). Anatomic and diffusion MRI data were collected for each child . A subset of thirty-three patients in this cohort had records of an eye exam, which were reviewed for a history of strabismus. Patients with MRI scans demonstrating cystic periventricular leukomalacia or grade III/IV intraventricular hemorrhage were classified as having brain injury. Clinical variables with a known association to strabismus or diffusion metrics were included in a multivariable logistic regression model. Diffusion tractography metrics were screened for association with strabismus on univariable analysis prior to inclusion in the regression model. RESULTS/ANTICIPATED RESULTS: A total of 17/33 (51.5%) patients developed strabismus. A logistic regression model including gestational age, PMA at MRI, retinopathy of prematurity (ROP) stage, brain injury, and fractional anisotropy of the right optic radiation was significant at the .001 level according to the chi-square statistic. The model predicted 88% of responses correctly. Each decrease of 0.01 in the fractional anisotropy of the right optic radiation increased the odds of strabismus by a factor of 1.5 (95% CI 1.03 – 2.06; p = .03). Patients with brain injury had 15.8 times higher odds of strabismus (95% CI 1.1 – 216.5; p = .04). Gestational age (OR 1.7; 95% CI 0.9 – 3.3; p = .1) and stage of ROP (OR 0.6; 95% CI 0.2 – 2.0; p = .4) were not significant predictors of strabismus in the multivariable model. DISCUSSION/SIGNIFICANCE: Our findings suggest that strabismus in VPT patients may be related to specific changes in brain structure in the neonatal period. The identified association between neonatal optic radiation microstructure and strabismus supports the possibility of using brain MRI in very preterm infants to prognosticate visual and ocular morbidity.

OBJECTIVES/GOALS: To determine whether cardioprotective effects observed in individuals taking dietary supplementation with eicosapentaenoic acid (EPA), an ω-3 polyunsaturated fatty acid, are realized by altering platelet function, and if these effects are mediated through the 12-lipoxygenase derived metabolite, 12-hydroxyeicosapentaenoic acid (12-HEPE). METHODS/STUDY POPULATION: Washed platelets or platelet rich plasma from healthy human donors were treated with EPA and 12-HEPE to assess their ability to inhibit platelet activation. Platelets were stimulated with agonists targeting different steps of the hemostatic response to vascular injury. Platelet aggregation, dense granule secretion, surface expression of integrin αIIbβ3 and P-selectin, and clot retraction were analyzed. To assess signaling through Gαs-GPCRs and protein kinase A activity, phosphorylation of vasodilator-stimulated phosphoprotein (VASP) was examined via western blot following treatment with EPA or 12-HEPE. RESULTS/ANTICIPATED RESULTS: EPA and 12-HEPE dose-dependently inhibit both collagen and thrombin-induced platelet aggregation. Furthermore, 12-HEPE more potently attenuates dense granule secretion and surface expression of platelet activation markers, integrin αIIbβ3 and P-selectin, in comparison to EPA. Plasma treated with EPA delayed thrombin-induced clot retraction, while 12-HEPE had no effect. Additionally, treatment with 12-HEPE increases phosphorylation of VASP, suggesting it could signal through the activation of the eicosanoid Gαs-GPCRs. DISCUSSION/SIGNIFICANCE: Here, we show for the first time that EPA directly inhibits platelet activation through its 12-LOX metabolite, 12-HEPE. These findings provide further insight into the mechanisms underlying the cardioprotective effects of EPA. A better understanding of current PUFA supplementations can inform treatment and prevention of cardiovascular diseases.

ABSTRACT IMPACT: It is our hope that a better understanding of the relationship between genetic variants that influence heart failure precursor traits will not only inform clinical care, but enable better assessment of inherited risk and will identify new biological targets for drug development. OBJECTIVES/GOALS: In this project, using a large-scale human genomic dataset with extensive phenotype data available, we intend to interrogate the known MTSS1 variants that have been associated with heart failure (HF) in previous GWAS studies in order to understand the directionality and mechanisms of their effects. METHODS/STUDY POPULATION: Data was obtained from the UK Biobank, a large prospective cohort of ˜500,000 patients across the United Kingdom with extensive phenotype data, including ˜50,000 patients with cardiac MRI and ˜200,000 with whole exome sequencing. We test for associations between genetic variants at the MTSS1 locus and HF precursor traits using logistic regression or linear regression, adjusting for age, gender, and principal components (PCs) of ancestry. For rare variant analyses we ‘bin’ rare variants (MAF < 0.01) using the software tool BioBin to aggregate low frequency genetic variants into single genetic units. RESULTS/ANTICIPATED RESULTS: Preliminary data have shown that variants in the known MTSS1 enhancer region which reduce MTSS1 expression are associated with smaller, more contractile hearts. We anticipate that common variants known to reduce enhancer activity will attenuate heart failure precursor traits, will be associated with a reduced risk clinical heart failure, and will favorably impact clinical outcomes once HF is established. We also anticipate that rare exonic variants predicted to impair MTSS1 function will attenuate heart failure precursor traits. DISCUSSION/SIGNIFICANCE OF FINDINGS: Through this work, we intend to take advantage of multiple novel approaches to better understand a complex disease process, identify a new potential therapeutic target (namely one that targets cardiac function), and to determine which patient subgroups will benefit from this our therapeutic interventions and why.