ABSTRACT IMPACT: This work examines the association between diabetes mellitus and latent tuberculosis infection among a cohort of household contacts exposed to active tuberculosis in Ethiopia, focusing attention on the need for further translational research to determine the mechanisms of susceptibility to Mycobacterium tuberculosis infection among individuals with diabetes and pre-diabetes. OBJECTIVES/GOALS: Diabetes mellitus (DM) is an established risk factor for active TB disease, but there is limited understanding of the relationship of DM and latent tuberculosis (LTBI). We sought to determine the relationship between DM or pre-DM with LTBI among household or close contacts (HHCs) of active TB cases in Ethiopia. METHODS/STUDY POPULATION: We conducted a cross-sectional study of the HHCs of index active TB cases enrolled in an ongoing TB Research Unit (TBRU) study in Addis Ababa, Ethiopia. HHCs of individuals with laboratory-confirmed TB had QuantiFERON ®-TB Gold Plus (QFT) and glycated hemoglobin (HbA1c) tests performed. LTBI was defined as a positive QFT and lack of symptoms. HbA1C results were used to define no DM (HbA1c <5.7), pre-DM (HbA1c 5.7-6.5%), and DM (HbA1c >6.5% or prior history of diabetes). Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) after adjustment for age, sex and HIV status as potential confounders. RESULTS/ANTICIPATED RESULTS: Among 466 HHCs, the median age was 29 years (IQR 23-38), 58.8% were female, 3.4% were HIV-positive, and median BMI was 20.9 kg/m^2 (IQR 18.9-23.8). Overall, 329 HHCs (70.6%) had LTBI, 26 (5.6%) had DM and 73 (15.7%) had pre-DM. Compared to HHC without DM, the prevalence of LTBI was higher in those with pre-DM (68.9% vs. 72.6%; OR 1.19, 95% CI 0.69-2.13) and those with DM (88.5%; OR 3.45, 95% CI 1.17-14.77). In multivariable analysis, there was a trend towards increased LTBI risk among HHCs with DM vs. without DM (OR 2.16, 95% CI 0.67-9.70) but the difference was not statistically significant. Among HHCs with LTBI, the median IFN-? response to TB1 antigen was modestly greater in those with DM (5.3 IU/mL; IQR 3.0-7.8) and pre-DM (5.4 IU/mL; IQR 2.0-8.4) compared to HHCs without DM (4.3 IU/mL; IQR 1.4-7.7). DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results suggest that DM may increase the risk of LTBI among HHCs recently exposed to active TB. Among those with LTBI, increased IFN-? antigen response in the presence of DM and pre-DM may indicate an exaggerated but ineffectual response to TB. Further investigation is needed to assess how dysglycemia impacts susceptibility to M. tuberculosis.

ABSTRACT IMPACT: Long-acting insulin containing protamine is more likely to be associated with skin depigmentation. OBJECTIVES/GOALS: An acquired disorder, skin depigmentation was found to be significantly correlated with diabetes. While a recent meta-analysis pointed at a possible similar pathogenesis, the possibility of vitiligo occurring as a drug-induced disease was never explored. This study aimed at elucidating whether utilization of specific insulins may play a role. METHODS/STUDY POPULATION: Records from the Medical Panels Expenditure Survey (MEPS) database made available by the Agency for Healthcare Research and Quality were used to identify all injectable insulin users (n=8867). ICD-9/10 codes were abstracted from the medical conditions files for all the subjects reporting any type of injectable insulin use (1996-2017). Skin depigmentation codes identified in our dataset were 709 and L81. Insulins were categorized based on duration of action, short-acting (SA), intermediate-acting (IA), and long-acting (LA), as well as based on formulation ingredients (zinc, protamine-zinc, other), and insulin combination (SA with or without IA/LA containing or not protamine-zinc). The association between skin depigmentation occurrence and insulin type and/or category was assessed by Fisher’s exact test. RESULTS/ANTICIPATED RESULTS: A total of 225 out of 8867 individuals were diagnosed with skin depigmentation. Incidence of skin depigmentation was 2.25% in SA users (n1=3606, p=0.355), 2.24% in LA users (n2=3910, p=0.337), and 2.39% in IA users (n3=4015, p=0.062). Occurrence of skin depigmentation was similar between users of insulin mono- or combo therapy (p=0.758). Interestingly, among IA insulins, insulin protamine-zinc insulin (n4=3992) distinguished as being mainly responsible for the association with the occurrence of skin depigmentation (p=0.062), whereas insulin zinc was not (n5=37, p=1.000). The highest skin depigmentation incidence was observed among Pacific Islanders (2.66%, p=0.110). Males distinguished by a skin depigmentation incidence of 2.34% vs. 1.91% in females (p=0.086). DISCUSSION/SIGNIFICANCE OF FINDINGS: We report that presence of protamine-zinc may play a role in the development of skin depigmentation. It is uncertain whether this risk may be shared equally by insulin users diagnosed with type 1 and type 2 diabetes. Of note, we observed a higher skin depigmentation incidence than that reported by community- (0.2%) or hospital-based (1.8%) studies.

ABSTRACT IMPACT: Our may suggest that delta hsTrop could be of prognostic value in patients with sepsis. OBJECTIVES/GOALS: - METHODS/STUDY POPULATION: We analyzed data of those presenting to the ED over an 18-month period with sepsis and at least one episode of hypotension after 1 liter of IV fluids. We performed a retrospective analysis using a cohort derived from modified inclusion and exclusion criteria from the CLOVERS study. The outcomes of patients found to have a delta (at least 6 pg/dL) in high sensitivity troponin T were compared to patients who did not have a delta or have a troponin level measured. We examined demographic and treatment characteristics of this cohort and the incidence of adverse outcomes were determined. We used multivariable logistic regression analysis to test the association of hsTrop and mortality. RESULTS/ANTICIPATED RESULTS: 778 patients met criteria to be included in the cohort. 279 patients had a change in high sensitivity troponins, an incidence of 35.9%. Patients with a delta were more likely to be older, male, and have a higher Charlson index than patients without a delta or those that had no troponin measured. They were also more likely to have a history of chronic lung disease, heart failure and hypertension. Change in high sensitivity troponins were associated with higher in-hospital mortality. When adjusted for age, gender, and Charlson Index, the association between a positive delta troponin and mortality remained statistically significant. DISCUSSION/SIGNIFICANCE OF FINDINGS: In patients with severe sepsis and septic shock, the presence of a positive or negative delta hsTrop at 2 hours is associated with increased mortality. Measurement of high sensitivity troponin early in the patient’s hospital course may have prognostic utility.

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.

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.

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

ABSTRACT IMPACT: This research highlights Adverse Childhood Experiences as a potential risk factor and intervention target contributing to the disproportionate number of individuals with sickle cell disease affected by asthma, a well-established catalyst to the increased morbidity and mortality impacting this high-risk population. OBJECTIVES/GOALS: Adverse Childhood Experiences (ACEs) are strongly associated with asthma. A disproportionate number of individuals with sickle cell disease (SCD) also have asthma. Asthma is strongly associated with increased SCD morbidity and mortality. This study compared the prevalence of asthma among children and adolescents with SCD with and without ACEs. METHODS/STUDY POPULATION: This retrospective cohort study involved 45 children and 30 adolescents with SCD. ACEs were captured using the Center for Youth Wellness Adverse Childhood Experiences Child and Teen Questionnaires, which encompass the original 10 ACEs as well as 7 (child) and 9 (teen) expert-recommended ('expanded') ACEs. ACE exposures were categorized as: Original 0-1 vs. ≥2; Original + Expanded 0-1 vs. ≥2. Asthma prevalence was compared among ≥2 and 0-1 ACE groups using the chi-square (or Fisher’s exact) test. A binary logistic regression was performed to predict the likelihood of asthma while adjusting for characteristics (age, household income and gender) that were statistically different among ACE comparison groups at baseline. RESULTS/ANTICIPATED RESULTS: Among the 45 child participants, 64% had a history of asthma; whereas 50% of teens had a history of asthma. Asthma prevalence was higher among teens with ≥2 vs. 0-1 Original ACEs (89% v. 33%, p=0.014). A history of ≥2 ACEs remained significant (p=0.024) among teens after adjusting for age, household income and gender. There was no significance in asthma prevalence among child ACE comparison groups. DISCUSSION/SIGNIFICANCE OF FINDINGS: Adolescents with ≥2 ACEs had a higher prevalence of asthma compared to subjects with 0-1 ACE. This study, coupled with the cumulative nature of ACEs and the graded-dose response relationship between ACEs and poor health outcomes, highlight the need for larger, longitudinal studies examining the relationship between ACEs, asthma and SCD outcomes.

ABSTRACT IMPACT: Our work provides guidance on whether dietary fat intake influences serum cholesterol levels in response to ketogenic diet therapy in adults with epilepsy. OBJECTIVES/GOALS: The modified Atkins diet (MAD) is used in the management of drug-resistant epilepsy in adults. Some patients on MAD show an increase in serum levels of total cholesterol and low-density lipoprotein (LDL) cholesterol. We explored whether dietary fat composition predicts short-term elevations in serum lipid levels in diet-naive adults who begin MAD. METHODS/STUDY POPULATION: Participants self-reported their diet intake with 3-day food records at baseline, 1 month and 2 months. Food records were analyzed using Nutrition Data System for Research software. Fasting serum levels of total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and triglycerides were also collected and LDL level calculated at baseline, 1 month, and 2 months. RESULTS/ANTICIPATED RESULTS: 38 patients submitted complete food records at each study visit (baseline, 1 month, and 2 month). Compared to baseline diet intake, there was a significant reduction in daily carbohydrate intake at 1 and 2 months (p<0.001) and a significant increase in daily fat intake at 1 and 2 months (p<0.001). There was also a significant increase in daily saturated fatty acid (SFA) intake at 1 and 2 months (p<0.001), daily mono-unsaturated fatty acid (MUFA) intake at 1 and 2 months (p<0.001), and daily cholesterol intake at 1 month (p<0.05) and 2 months (p<0.001), but no change in daily poly-unsaturated fatty acid (PUFA) intake over time. Compared to baseline, there was a significant increase in serum LDL at 1 month (p<0.001) and 2 months (p<0.01) and an increase in serum TC at 1 month (p<0.01) but not 2 months. DISCUSSION/SIGNIFICANCE OF FINDINGS: Despite a significant increase in total fat, saturated fat and mono-unsaturated fat intake as well as an increase in total cholesterol and LDL levels following MAD initiation, dietary fat composition appears to minimally predict serum lipid values in the short term.

ABSTRACT IMPACT: Obesity is a quickly growing pandemic that negatively impacts health, and clinicians and clinics must employ all evidence-based tools (such as self-monitoring) to help patients control their weight. OBJECTIVES/GOALS: The objective of this study was to understand patient and parent perspectives on using daily self-weighing for adolescents with obesity who are seeking obesity treatment. The secondary objective was to understand perspectives on connecting smart-scales to the electronic medical record for messaging, feedback, and reminders between visits. METHODS/STUDY POPULATION: Thirty adolescents with obesity who were seeking obesity treatment at a tertiary pediatric weight management clinic were recruited into a single-arm feasibility study to create and assess a connection between blue-tooth scales and the electronic medical record. These adolescents and their parents were then approached about conducting exit interviews about their experience in the feasibility study -- their perspectives on connecting bluetooth scales connected to the electronic health record and using daily self-weighing at home to help them reach their healthy weight goals. The interviews were conducted by a trained interviewer who was not a PI or Co-I on the feasibility study, recorded, and transcribed. The interviews were organized on themes including technical challenges, mood, stress, clinic feedback. RESULTS/ANTICIPATED RESULTS: The main theme expressed by participants and parents was related to past experiences of their weight loss journey. Sub-themes included: technical challenges with apps, parental involvement in weighing, being told by clinicians to weigh, and intervention impact. Most parents desired more directions and help with setting up the app connection to the EHR. Most parents did not ask their child daily about their weight status as they did not want to cause stress. Some adolescents found it stressful when parents asked about daily weight status; others found it helpful or at least not stressful. Most participants had never been advised by their clinician to regularly self-weigh. Most found it helpful to monitor their weight regularly. Most asked for reminders from clinic to weight and for feedback on weight between visits. DISCUSSION/SIGNIFICANCE OF FINDINGS: Overall, adolescents with obesity reported self-weighing as being helpful and most wanted some, but not daily, involvement from parents. Most parents wanted additional technological support to create the scale set-up. Nearly all parents and adolescents wanted the weights to be connected to clinic, and for there to be feedback from clinic on weight.

ABSTRACT IMPACT: Implementation of digital and mobile applications in clinical research crisis response protocols can mitigate their impact on clinical research. OBJECTIVES/GOALS: Crisis management is fundamental to ensuring the protection of human subjects during a clinical trial. Mobile apps have the capacity to allow for quick access to crisis response plans and can serve to mitigate their impact on clinical research. Electronic data capture tools can be used to create digital applications for such a response. METHODS/STUDY POPULATION: The Clinical Research Center at Rutgers University transferred a paper-based crisis management response plan to a digital mobile application format using Vanderbuilt’s Research Electronic Data Capture Tool (REDCap). REDCap’s branching logic allowed for programming a decision support functionality to guide users through 3 specific crises. (1) threatening or aggressive study subject behavior; (2) clinical research center break in or theft; and (3) adverse event observed for ongoing or closed clinical research study. Applicable U.S. Code of Federal Regulations, IRB guidelines, institutional policies and procedures were also used as a component of the mobile development. RESULTS/ANTICIPATED RESULTS: The Crisis Management Decision-Support Portal within the Clinical Research Center has an interactive structure. The use of branching logic demonstrates the ability for users to answer each question and be guided to appropriate responses specific to selected criteria related to each event. The tool contains a self-correct function by providing a reset option after answering each section. The portal itself can be accessed using any computer or cellphone with an internet connection. It provides the users with appropriate criteria to determine to exact communication and management protocols for reporting for the crisis event they are witnessing. As users access the portal, usage data can be collected, tracked, and stored. DISCUSSION/SIGNIFICANCE OF FINDINGS: The REDCap platform offers the opportunity to digitize crisis management protocols that ensure professionals have easy access to appropriate responses to crises at the center. The use a digital application rather than paper allows for a CTSA sponsored hub to mitigate damage, simply build new protocols, modify existing protocols, and track usage.

ABSTRACT IMPACT: My work evaluates the impact of electronic data capture/eSource on several aspects of clinical trial efficiency and scale, aiming to demonstrate how eSource can be used to improve the way we run clinical trials. OBJECTIVES/GOALS: Using eSource may increase the efficiency of data collection in clinical trials. However, adoption of eSource has been slow. We reviewed over 100 large multinational clinical trials to analyze how eSource use correlated with trial size, sponsor collaborations, time to complete, and time to publication. METHODS/STUDY POPULATION: We searched ClinicalTrials.gov for completed, interventional, Stage II-IV clinical trials with posted results and an uploaded study protocol document. This produced 3,962 trials. We identified all studies with over 1,200 participants and sites in multiple countries (or at least 100 sites in one country). After eliminating ten studies with duplicate protocols, we had a database of 123 trials. From the ClinicalTrials.gov listing, the study protocol, and any published papers, we determined the start, end, and publication dates, data collection protocol, sponsors and collaborators, and any reasons given for delays for each trial. We performed statistical tests comparing trial delay, participant and country count, and collaboration status (yes or no) between the two groups (eSource users and non-eSource users). RESULTS/ANTICIPATED RESULTS: Of our 123 trials, 60 (48.7%) used eSource, 48 (39.1%) used paper source documentation, and 15 (12.2%) used some combination. We found no statistically significant difference between eSource and non-eSource trials in terms of trial delay (p=0.43), time to publish (p=0.33), collaboration status (p=0.54), number of participants (p=0.36), or number of countries (p=0.12). However, our analysis was limited by what data was publically available. To investigate the effects of eSource on site efficiency, data accuracy, and data security, which are three major factors behind the FDA’s 2013 eSource recommendation, we would need access to proprietary information from trial sponsors. DISCUSSION/SIGNIFICANCE OF FINDINGS: The use of eSource in large multinational clinical trials is not correlated with a change in time to completion or publication nor a higher number of participants or countries. We aim to acquire proprietary data to further analyze the impacts of eSource on trial efficiency, data accuracy, and data security.

ABSTRACT IMPACT: The findings suggest that targeting parenting stress in combination with psychoeducation on nutrition and physical activity may have positive effects in improving healthy food choices such as reduction of fast food intake, which may in turn impact the health of toddlers and their families. OBJECTIVES/GOALS: Parent stress is associated with a myriad of unhealthy behaviors including overeating, decreased physical activity, which contribute to increased weight. Several programs have aimed to increase education of nutrition, but few have focused on parent stress to improve healthy food intake. The present study assessed parent stress and fast food intake. METHODS/STUDY POPULATION: Parents who have obesity and had a toddler in the age group of 2-5 years were enrolled for a preventive intervention study to assess the effect of a parent-based intervention to improve family health choices and reduce childhood obesity risk. The sample included 105 participants, mean age 34.80 (6.27) years old, mean body mass index (BMI) 35.51 kg/m2, 39.0% Non-Hispanic White, 20.0% Non-Hispanic Black, 22.9% multiracial, 12.4% Hispanic, and 5.7% other. Stress was assessed using the Perceived Stress Scale (PSS) to assess overall general stress and the Parenting Stress Index (PSI) to assess parent-specific stress. Chaos in the home and fast food intake were also assessed using self-report surveys. RESULTS/ANTICIPATED RESULTS: Preliminary results are based on available data as of October 2020, data collection and recruitment are still in progress. There was a significant correlation between fast food intake with PSS (r=.18, p=.04), chaos (r=.24, p=.02), and PSI (r=.25, p=.01). Using a hierarchical regression model, we entered home chaos in the first block which explained a significant amount of the variability (R2= .06, p=.04). PSS was entered in the second block, which was not significant (R2 change=.01, p=.50), and in the final block PSI was entered and was significant (R2 change=.13, p <.01). DISCUSSION/SIGNIFICANCE OF FINDINGS: The data indicate that parenting stress uniquely predicts fast food intake above and beyond what could be explained by home chaos and general perceived stress. Future analyses will assess a parent-based intervention targeting stress reduction to improve weight and health for the parent and their toddlers in order to reduce childhood obesity risk.

ABSTRACT IMPACT: Impaired neuromuscular control could lead to the failure in activation and deactivation of the target muscles in a timely manner, with the concurrence of activities of non-targeted muscles. OBJECTIVES/GOALS: Stroke leads to impaired capacity to manipulate objects with the hand in terms of timing and strength of grasp. The influence of abnormal coupling across more proximal arm muscles post stroke on the failure in normal functioning of finger flexor muscle activity is of interest to investigate. METHODS/STUDY POPULATION: We have recruited 12 participants with stroke hemiparesis in the sub-acute or chronic stage. Motor impairment of the arm was assessed using electromyography (EMG) and the Fugl-Meyer Upper Extremity (FMUE) assessment. Participants were requested to flex and relax the metacarpophalangeal (MCP) joints against motorized resistance in response to audible tones to determine timing and strength during flexion. They were asked to flex maximally, as quickly as possible, in response to the first of a pair of tones, and relax as quickly as possible after the second tone. Delays in initiation and termination were evaluated using EMG responses versus a predefined threshold. RESULTS/ANTICIPATED RESULTS: We anticipate greater delays in grasp initiation as well as in grasp termination in participants with a greater extent of abnormal coupling across more proximal muscles of the upper extremity in comparison to participants with a less extent, using the results of the FMUE assessment. Also it is expected that participants with a greater extent of the flexion synergy produce a less extent of force generation. The EMG results will show that activities of more proximal arm muscles precede the initiation of MCP flexion and their activity termination precedes that of MCP flexion, significantly more in participants with a greater extent of the flexion synergy. DISCUSSION/SIGNIFICANCE OF FINDINGS: The flexion synergy over the arm following stroke affects the timing and strength of hand grasp. Impaired neuromuscular control could lead to the failure in activation and deactivation of the target muscles in a timely manner, with the concurrence of activities of non-targeted muscles.

ABSTRACT IMPACT: This study helps translate investigational bedside optical coherence tomography into improved diagnosis and care of preterm infants at risk for retinopathy of prematurity. OBJECTIVES/GOALS: In retinopathy of prematurity screening, fundus photography may be of limited quality in eyes with dark fundus pigmentation (FP). The goal of this study was to evaluate the impact of FP on overall scan quality and retinal layer visibility on investigational bedside optical coherence tomography (OCT) in preterm infants. METHODS/STUDY POPULATION: We analyzed 846 OCT scans captured prospectively from 188 eyes of 94 preterm infants enrolled in the BabySTEPS study (NCT02887157). Trained ophthalmologists, masked to OCT findings, determined FP (blond, medium, or dark). Expert graders, masked to FP, evaluated OCT images for: 1) overall OCT quality (excellent, acceptable, poor, or unusable); and 2) all age-appropriate retinal layers visible (yes or no). To assess the association of FP with OCT quality (excellent/acceptable or poor/unusable) and retinal layer visibility, we performed multivariable logistic regression modeling, adjusting for biologic and demographic confounders and correlations from repeated OCT scans and paired eyes. RESULTS/ANTICIPATED RESULTS: Mean birthweight was 964 (SD=283) grams, mean gestational age was 27.8 (SD=2.6) weeks, 48 (51%) infants were male, and 51 (54%) were non-white. On exam, 72 (38%) eyes had blond FP, 92 (49%) had medium, and 24 (13%) had dark. OCT quality was excellent or acceptable in 725 scans (86%) and all age-appropriate retinal layers were visible in 781 scans (92%). Compared to eyes with blond FP, eyes with medium and dark FP did not have higher odds of poor/unusable OCT scan quality (adjusted OR 0.87 [95% CI 0.50-1.48] and 0.49 [95% CI 0.16-1.55], respectively) or not all age-appropriate retinal layers visible on OCT (adjusted OR 1.17 [95% CI 0.39-3.51] and 0.57 [95% CI 0.15-2.20], respectively). DISCUSSION/SIGNIFICANCE OF FINDINGS: Medium and dark FP did not impact overall scan quality or age-appropriate retinal layer visibility on investigational bedside OCT in preterm infants. This study supports the feasibility of using OCT to analyze retinal microanatomy in diverse populations of preterm infants with a range of FP.

ABSTRACT IMPACT: By restoring the gut microbiota in patients with acute myeloid leukemia exposed to antibiotics, we will reduce infections during and after curative-intent chemotherapy. OBJECTIVES/GOALS: Infection is a leading cause of death in acute myeloid leukemia (AML). Antibiotics disrupt the gut microbiota, promoting secondary infections. Through a double-blind randomized placebo-controlled phase 2 trial, we will determine whether microbiota restoration using fecal microbiota transplantation (FMT) prevents infections in AML patients. METHODS/STUDY POPULATION: 72 intensively treated AML patients at our institution are randomized in a 2:1 ratio to FMT (arm A) or placebo (arm B). After completing each course of antibacterial antibiotics, patients receive one study treatment. Up to 3 study treatments are administered over 3 months. FMT is delivered as a third-party oral product containing microbiota (˜5x10^11 bacteria) in 4-6 capsules. Stool samples are collected before and after each study treatment. The primary endpoint is 4-month overall infection rate. 16S rRNA gene sequencing of stool samples is used to determine specific taxa that are under- or over-represented in samples preceding infections and compare the two arms for key microbiome features including diversity and composition. Bloodstream infection within 7 days after FMT counts towards stopping rule. RESULTS/ANTICIPATED RESULTS: Five patients have been enrolled: 4 have received 1 dose and 1 received 2 doses. The only adverse event (possibly related to study treatment) has been grade 1 abdominal pain in 1 patient. Notably, no bloodstream infection has occurred. All planned samples have been collected and are sequenced in batches. We expect arm A patients to experience fewer infections and fewer intestinal blooms of pathobionts, and both arms to experience intestinal blooms before specific infections. An interim efficacy analysis will be performed at half total enrollment. DISCUSSION/SIGNIFICANCE OF FINDINGS: Current supportive care during intensive chemotherapy is fundamentally anti-microbial and results in dysbiosis, with detrimental consequences. We will establish the evidence for FMT as a restorative strategy in AML patients. This is the first randomized placebo-controlled trial of repeated FMT, with potential implications to other cancers.

ABSTRACT IMPACT: A short treatment of 8 obese postmenopausal women with conjugated estrogens and bazedoxifene does not alter insulin sensitivity or ectopic fat but increases serum markers of hepatic de novo lipogenesis and production of triacylglycerides. OBJECTIVES/GOALS: Combining conjugated estrogens (CE) with the selective estrogen receptor modulator bazedoxifene (BZA) is a novel, orally-administered menopausal therapy. We investigated the effect of CE/BZA on insulin sensitivity, energy metabolism, and serum metabolome in postmenopausal women with obesity. METHODS/STUDY POPULATION: We conducted a randomized, double-blind, crossover pilot trial, testing the effect of CE/BZA on cardiometabolic health in postmenopausal women. Eight postmenopausal women (age 50-60 y, BMI 30-40 kg/m2) were randomization to an 8-week CE/BZA or placebo treatment separated by an 8-week washout period [NCT02274571]. The primary outcome was insulin sensitivity (hyperinsulinemic-euglycemic clamp), while secondary outcomes included body composition (DXA); resting metabolic rate (RMR); substrate oxidation (indirect calorimetry); ectopic lipids (1H-MRS); fat cell size, adipose and skeletal muscle gene expression (biopsies); inflammatory markers; and serum metabolome (LC/MS). RESULTS/ANTICIPATED RESULTS: CE/BZA had no effect on insulin sensitivity, body composition, ectopic fat, or substrate oxidation, but resulted in a non-significant increase in RMR (basal: p=0.06; high-dose clamp: p=0.08) compared to placebo. CE/BZA increased serum high-density lipoprotein cholesterol. CE/BZA also increased serum diacylglycerol (DAG) and triacylglycerol (TAG) species containing long-chain saturated, mono- and polyunsaturated fatty acids (FAs), and decreased long-chain acylcarnitines. These findings possibly reflect increased hepatic de novo FA synthesis and esterification into TAGs, and decreased FA oxidation, respectively (p<0.05). CE/BZA increased serum phosphatidylcholines, phosphatidylethanolamines, ceramides, and sphingomyelins, possibly reflecting the increase in lipoproteins (p<0.05). DISCUSSION/SIGNIFICANCE OF FINDINGS: A short treatment of postmenopausal women with CE/BZA did not alter insulin action or ectopic fat, but increased markers of hepatic de novo lipogenesis and TAG production. Study limitations include a small sample size and short treatment period. A larger, fully powered study is needed to validate the potential metabolic benefit of combining CE with BZA.

ABSTRACT IMPACT: Increase understanding of the types of sponsors responding to the COVID-19 pandemic. OBJECTIVES/GOALS: The COVID-19 pandemic has impacted millions of lives globally. To learn more about this disease and find potential diagnostic, treatment, and preventative products, the healthcare community has initiated a staggering number of clinical trials. Clinicaltrials.gov was reviewed to determine the types of sponsors who are conducting COVID-19 studies. METHODS/STUDY POPULATION: Clinicaltrials.gov was searched using terms ‘COVID-19’ and ‘SARS-Cov-2’. Search results were further defined to include only ‘Interventional’ studies. Of these, only studies with sites located in the United States were selected and for which the ‘Condition’ included at least one of the following terms: ‘COVID’, ‘COVID-19’, ‘Coronavirus’, ‘SARS-Cov-2’, ‘SARS’, or ‘2019-nCoV'. Study sponsors were then categorized as: (1) commercial, (2) academic, or (3) other, based on ‘Sponsor’ information within each study listing. A Google search was conducted for any sponsor that was not easily categorized to obtain additional information to support the proper assessment of sponsor type. The types of sponsors were analyzed over time using the ‘First Posted’ date of each study listing. RESULTS/ANTICIPATED RESULTS: A total of 3662 studies were retrieved, of which 2075 were ‘Interventional’ studies. The studies were further reduced to 681 studies by including only United States sites and the desired ‘Condition’. The percentage of studies from this refined dataset, by sponsor type, were found to be 63% academic, 34% commercial, and 3% other. The relationship between time and sponsor type demonstrated that academic sponsors had the highest percentage of study postings in the first month (March) of the COVID-19 pandemic compared to commercial and other sponsors. Following this first month, academic study postings gradually declined, while commercial sponsors had an increase in postings per month into July, followed by a gradual decline. Few other sponsor type postings were made and occurred primarily in August. DISCUSSION/SIGNIFICANCE OF FINDINGS: The number and timing of listings may be a reflection of study intention and regulatory pathway requirements. Additional variables, such as inconsistent terminology, collaborators, funding, and study start date may influence results. Further analysis may reveal how modification of listing information may result in expedited pandemic response.

ABSTRACT IMPACT: We seek to determine which lymph nodes drain the human brain. OBJECTIVES/GOALS: Lymphatic vessels train lymphatic fluid from the central nervous system (CNS), but the specific lymph nodes that these vessels drain to remains unknown in humans. We intend on using technetium tilmanocept (TcTM)to map the draining lymph nodes of the CNSin humans. METHODS/STUDY POPULATION: Patients having a tumor resected are eligible for the trial. All patients will have TcTM injected intracranially after tumor resection. Six patients will be enrolled in Cohort 1 to define the time course of drainage to the lymph nodes. Patients in Cohort 1 will be imaged with planar LS within 7 hours of injection and the following day. Either 12 or 24 patients will be enrolled into Cohort 2 to localize the draining lymph nodes with SPECT-CT. The optimal imaging timepoint from Cohort 1 will be used for Cohort 2. Patients in Cohort 2 will be stratified depending on if their tumor is in the frontal, parietal, occipital, or temporal lobe. RESULTS/ANTICIPATED RESULTS: We anticipate that we will detect TcTMin the deep cervical lymph nodes after injection into the brain. It is unclear exactly which lymph nodes the tracer will go to. We hypothesize that the results among patients will be similar, but interindividual variation is a possibility. Furthermore, patients with disease in different lobes of the brain may have different lymph drainage patterns. DISCUSSION/SIGNIFICANCE OF FINDINGS: We seek to answer a fundamental question of human anatomy: what lymph nodes drain the human brain? Additionally, knowing which nodes drain the human brain could shape future research of immunotherapy in patients with brain cancer or autoimmune disease such as multiple sclerosis.

ABSTRACT IMPACT: This work will impact participants of clinical trials by better informing them of their trial’s results and their important role within the clinical research process. OBJECTIVES/GOALS: This project aims to equip researchers with an online tool for the development, dissemination, and collection of participant feedback for plain language clinical trial (CT) result summaries (PLCTRS). PLCTRS ensure that participants fully understand their trial’s results and their role in the CT process. METHODS/STUDY POPULATION: This online development platform is a web application made with CSS, HTML, and JavaScript. First, general trial identification information including study aims and eligibility will be input by researchers. Then, they will be prompted with tips and suggestions for composing in plain language and to ensure inclusion of all essential trial information. Next, the platform will disseminate this writing electronically to participants. Participants then provide meaningful feedback on the platform about their comprehension for the researcher, which the platform will aggregate and summarize for revisions. This process of drafting and feedback is repeated until a satisfactory PLCTRS is finalized. RESULTS/ANTICIPATED RESULTS: The anticipated results of this project are overall improved comprehension of clinical trial results by participants. This comprehension will be measured by participants ability to answer certain questions not only regarding trial outcomes, but also about the trial in general. For instance, before and after interacting with the PLCTRS, trial participants will be asked if they can identify which investigational drug was being studied and its possible side effects. This project could anticipate identification of trial elements and results deemed difficult to comprehend by participants; thus they would be better informed after interacting with the platform. DISCUSSION/SIGNIFICANCE OF FINDINGS: This project will ensure that participants better comprehend the trials they participated in beyond the required informed consent process - which only covers their comprehension prospectively. This project seeks to address the gap of ensuring participant comprehension retrospectively.

ABSTRACT IMPACT: The proposed research study will provide critical pilot data on the effect of using the prebiotic (HAMS-AB) on the gut microbiome profile, Beta-cell function and immune markers in humans with T1D. OBJECTIVES/GOALS: The overall objective of this study is to assess how the prebiotic high amylose maize starch that has been acetylated and butyrylated (HAMS-AB) impacts the gut microbiome profile, short chain fatty acid (SCFA) production, glycemia, Beta-cell function/health and immune responses in newly diagnosed youth with type 1 diabetes (T1D). METHODS/STUDY POPULATION: We are performing a pilot randomized cross-over trial. We plan to recruit 12 newly-diagnosed T1D youth with residual Beta-cell function between 12-16 years of age. We will profile the gut microbiome using metagenomics, measure stool SCFA levels using mass spectrometry, assess glycemia using continuous glucose monitoring, assess insulin production using mixed meal tolerance testing, assess Beta-cell stress using proinsulin/C-peptide levels, and test immune responses by examining cytokine levels and frequency, phenotype and function of T cell markers in peripheral blood. RESULTS/ANTICIPATED RESULTS: Thus far, we have enrolled 3 participants, 1 has completed the study. Baseline assessments indicate that we have technical feasibility of performing the above studies and measurements. Recruitment and enrollment are ongoing. We hypothesize that the use of HAMS-AB in newly diagnosed youth with T1D will (i) improve the gut microbiome profile, (ii) increase SCFA production, (iii) improve overall glycemia and Beta-cell function and (iv) modulate the immune system and mitigate autoimmunity. DISCUSSION/SIGNIFICANCE OF FINDINGS: Given the failure to develop a cure for T1D despite multiple completed intervention studies and the unknown long-term effects of immune-modulatory therapy on those at risk for or those diagnosed with T1D, prebiotics such as HAMS-AB may offer a simple, safe, yet inexpensive and tolerated dietary alternative approach to mitigating disease.