OBJECTIVES/GOALS: CTSA Program hubs provide a wide range of research support services (funding, training, consultations, etc.) to individuals and teams. The CTSA Program hub at Columbia University seeks to identify best practices across CTSA hubs in how they facilitate researchers to identify, navigate, and access services at complex academic medical centers. METHODS/STUDY POPULATION: o A landscape analysis across CTSA Program hub websites was conducted during December 2021-February 2022, with the goal of assessing the availability of research navigation services and the ease of accessing and requesting research support services at each hub. Websites of 66 CTSA hubs were accessed and browsed for the following: 1) if a research navigation or concierge service was available; 2) how to request and apply to use common services such as pilot funding, biostatistics, clinical research services; 3) if there was a contact form and/or email address for general inquiries. Binary coding (1=Yes, 2=No) was used to track and summarize if these features were available, and then further classification and observations were noted into the full data set. RESULTS/ANTICIPATED RESULTS: The landscape analysis determined that 68% of CTSA hubs offer a form of research navigation including consultative models (personalized guidance, studios) and web-based models (self-service web portals, graphics, toolkits). Consultative models could be classified into three levels of support ranging from general information sharing to providing scientific expertise to convening more intensive studio sessions. 92% of CTSA hubs have at least 1 system in place for researchers to request services with a majority of hubs using a mix of tools and systems. In addition, 36% of hubs have additional general contact forms and 75% have general email addresses to assist researchers in obtaining more information. DISCUSSION/SIGNIFICANCE: There is a relative lack of data and information on the effectiveness of different research navigation models across the CTSA network, and barriers for researchers to identify services remain (Elworth et al). Our team is planning additional evaluations including interviews with leaders at other CTSA hubs and researchers and trainees at Columbia.

Objectives/Goals: Dravet syndrome is a developmental and epileptic encephalopathy associated with refractory seizures and a high risk of sudden unexpected death in epilepsy. A pathogenic biallelic variant in SCN1B, SCN1B-p.R98C, was identified in three patients with Dravet syndrome. Here we investigate SCN1B-p.R98C on neuronal function in vivo. Methods/Study Population: Scn1b-p.R98C mice were previously generated using CRISPR-Cas9 gene editing. Homozygous animals exhibit increased susceptibility to hyperthermia induced seizures at postnatal day (P) 15, 100% expression of spontaneous generalized seizures by P30, and ~20% undergo SUDEP by approximately P60. Here we examined the neuronal phenotype of P17–28 male and female Scn1b-p.R89C mice. We used whole-cell patch clamp electrophysiology approaches to measure effects of the variant on passive membrane properties, intrinsic excitability, and single action potential properties of parvalbumin positive (PV+) interneurons and pyramidal neurons in layers 5/6 of the somatosensory cortex and CA1 region of the hippocampus. Wild-type littermates were used as controls. Results/Anticipated Results: Our results show no differences between genotypes in any measure for somatosensory cortical PV+ interneurons or pyramidal neurons. In the CA1 region of the hippocampus, we found no differences for any measure in PV+ interneurons. In contrast, CA1 pyramidal neurons were hyperexcitable, however, with no changes in passive membrane properties or single action potential properties. Discussion/Significance of Impact:

OBJECTIVES/GOALS: We seek to develop a 3D perfusion culture imaging plate for human fecal bacteria co-culture with epithelial cells in a structure that mimics the gut epithelium. We will develop this system for use with patient fecal samples to characterize patient risk of developing cancer. METHODS/STUDY POPULATION: E. coli NC101, a strain that harbors the pks gene island, produces the genotoxin colibactin which causes DNA damage that can lead to colorectal cancer development. The genotoxic ability of this bacterium is dependent upon cell-to-cell contact. Here, we present 3D printed E. coli NC101 and intestinal epithelial cells (IEC-6) in a perfusion imaging plate, enabling visualization of the cytotoxic effects of the bacteria in real time using confocal microscopy, in combination with flow cytometry analysis for cell cycle arrest (a surrogate marker of DNA damage). RESULTS/ANTICIPATED RESULTS: 40,000 IEC-6 cells were 3D printed in a cylindrical layer in our triple well imaging plate. The cells were infected at an MOI of 100 for 18 hours and time lapse images of the infection were recorded by confocal microscopy. The cells were then harvested for analysis by flow cytometry for cell cycle arrest as a measure of DNA damage. Our images and flow cytometry data show that E. coli NC101 co-localizes with IEC-6 cells and causes cell cycle arrest in phase G2 (infected %G2 = 40.1), compared to uninfected cells (%G2 = 24.7, P = 0.034). Mutant strains lacking adhesion protein FimH or the ability to produce colibactin do not cause G2 cell cycle arrest (P = 0.844 and P = 0.644, respectively). DISCUSSION/SIGNIFICANCE OF IMPACT: We are able to recapitulate the DNA damage phenotype of E. coli NC101 in our 3D culture system. We show here that host-microbe interactions leading to cancer can be modeled in our 3D perfusion system, and we will next use patient fecal samples in our culture system.

ABSTRACT IMPACT: Because diabetes disproportionately affects residents in the Deep South, identifying factors increasing the risk of hospital readmissions unique to this population can translate to tailored interventions and strategies to improve transitions of care and patients’ health outcomes. OBJECTIVES/GOALS: Patients with diabetes (PWD) are susceptible to hospital readmissions due to inadequate transitions of care (TOC). To better understand how to improve TOC, the objective of the study is to identify factors associated with readmissions among PWD in Alabama disproportionally affected by diabetes. METHODS/STUDY POPULATION: This retrospective cohort study utilizes electronic health record data from an urban health system in Alabama. The study population includes adults (≥18 years old) diagnosed with diabetes who were hospitalized between 2016 and 2020. Women who are pregnant during hospitalization or diagnosed with gestational diabetes are excluded. Patient’s index hospitalization is identified with a 3-month washout period preceding admission. The primary outcome is all-cause 30-day readmission. Characteristics are compared between patients with and without readmissions. Factors significantly associated with readmissions are identified with multiple logistic regression, adjusted for potential confounders. RESULTS/ANTICIPATED RESULTS: The sample size is expected to be around 30,000 individual PWD. Anticipated results include estimation of the all-cause 30-day readmission rate experienced by the PWD in Alabama. It is expected that various factors will be associated with either higher or lower odds of readmission, interpreted via odds ratios and 95% confidence intervals. Factors investigated are driven by previously identified risk factors of readmission from the literature, including but not limited to sociodemographic variables, lab values (A1C, glucose, serum albumin, serum sodium, etc.), vital signs (blood pressure), comorbidities, medications, length of stay, insurance coverage, geographic location, and social history. DISCUSSION/SIGNIFICANCE OF FINDINGS: Findings will establish evidence-based knowledge about TOC for PWD in the Deep South, specifically Alabama. Identifying factors associated with readmissions among PWD in Alabama will inform TOC intervention studies tailored to populations in the Deep South to effectively mitigate readmissions.

OBJECTIVES/GOALS: The goal of the CTSA consortium is to move scientific discoveries to clinical application. Translational science (TS) focuses on the process by which this happens, and NCATS supports pilot projects that propose TS questions. We are developing a rubric to guide program managers’ability to discriminate between TS and translational research (TR). METHODS/STUDY POPULATION: The CTSA External Review Exchange Consortium (CEREC) and CEREC II are reciprocal review collaborations between CTSA hubs that identify reviewers for each other’s pilot grant applications. CEREC and CEREC II partners developed a 31-item rubric, based on NIH’s Translational Science Principles, for discriminating pilot TS grant applications from those proposing TR. The hubs contributed proposals pre-selected as either TS or TR projects. Then, experienced reviewers and/or program administrators from the hubs used the rubric to score each of the proposals. Reliability of the rubric will be assessed using inter-rater reliability (% agreement and kappa). To identify which of the items in the rubric best discriminate between TS and TR, Item Response Theory analysis will be employed. RESULTS/ANTICIPATED RESULTS: Ten CEREC participating hubs submitted 30 applications: 20 TS proposals and 10 TR proposals. Twenty-two reviewers from 12 CEREC hubs evaluated the applications by using the scoring rubric; at least two reviewers evaluated each proposal. The results of the analyses will describe the reliability of the rubric and identify which of the seven TS Principles are most useful for distinguishing between TS and TR pilot grant proposals. Ultimately, this work will yield a scoring rubric that will be disseminated throughout the CTSA network to facilitate the screening of TS applications. DISCUSSION/SIGNIFICANCE: Optimizing research processes is critical to ensure that scientific discoveries are integrated into clinical practice and public health policy as rapidly, efficiently, and equitably as possible. By appropriately identifying and funding TS projects, CTSA hubs can accelerate the impact of clinical and translational research.

ABSTRACT IMPACT: This study has implications for understanding early developmental mechanisms of ADHD and for guidelines regarding safe use of acetaminophen during pregnancy. OBJECTIVES/GOALS: Prenatal acetaminophen exposure has been associated with childhood attention-deficit hyperactivity disorder (ADHD), but the underlying mechanism is unknown. This prospective birth cohort study aims to identify linkages between specific metabolites in umbilical cord plasma and the association of prenatal acetaminophen exposure and ADHD. METHODS/STUDY POPULATION: The sample was a subset of the Boston Birth Cohort that included 583 mother-newborn dyads followed at Boston Medical Center from 1998 to 2018. Metabolites were measured from cord plasma collected at birth. Based on existing literature, the analyses focused on candidate metabolites involved in neuroendocrine, inflammation, and oxidative stress pathways. The outcome was physician-diagnosed ADHD between the ages of 3 and 16 years. Exploratory analyses and multiple logistic regressions were used to examine the association of these candidate metabolites with both unmetabolized cord plasma acetaminophen levels and with incident risk of ADHD, adjusting for covariates of maternal and child characteristics. RESULTS/ANTICIPATED RESULTS: Of the 583 children, 257 had ADHD and 326 had neurotypical development. Two promising results have been found thus far. 5-methoxytryptophol (5-MTX), a neuroendocrine molecule which also has antioxidant and immunomodulatory properties, was inversely associated with acetaminophen and ADHD risk. For children below the median cord 5-MTX level, the odds of ADHD were 3.29 (95% CI [1.56, 7.16], p=0.002) for the third tertile of acetaminophen compared to the first tertile. This association attenuated among those above the median 5-MTX level: 2.23 (95% CI [0.98, 5.21], p=0.059), suggesting a protective effect. Tryptophan, an essential amino acid and precursor of serotonin, was positively associated with acetaminophen and ADHD. Next steps include mediation analysis with tryptophan and analyses for other metabolites. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study identifies cord plasma metabolites as possible modifiers or mediators linking prenatal acetaminophen exposure and childhood ADHD, which may offer insight into a mechanistic pathway. The study findings have implications for FDA, clinical, and public health guidelines regarding safe use of acetaminophen during pregnancy.

OBJECTIVES/GOALS: Spinal cord stimulation (SCS) is an intervention for patients with chronic back pain. Technological advances have led to renewed optimism in the field, but mechanisms of action in the brain remain poorly understood. We hypothesize that SCS outcomes will be associated with changes in neural oscillations. METHODS/STUDY POPULATION: The goal of our team project is to test patients who receive SCS at 3 times points: baseline, at day 7 during the trial period, and day 180 after a permanent system has been implanted. At each time point participants will complete 10 minutes of eyes closed, resting electroencephalography (EEG). EEG will be collected with the ActiveTwo system, a 128-electrode cap, and a 256 channel AD box from BioSemi. Traditional machine learning methods such as support vector machine and more complex models including deep learning will be used to generate interpretable features within resting EEG signals. RESULTS/ANTICIPATED RESULTS: Through machine learning, we anticipate that SCS will have a significant effect on resting alpha and beta power in sensorimotor cortex. DISCUSSION/SIGNIFICANCE OF IMPACT: This collaborative project will further the application of machine learning in cognitive neuroscience and allow us to better understand how therapies for chronic pain alter resting brain activity.

OBJECTIVES/GOALS: Neonatal hypoglycemia is seen in 65% of maternally diabetic pregnancies, and can lead to severe neurological damage. Neonatal glycemia may also be an indicator of placental function in these pregnancies. The purpose of this study is to identify patterns of neonatal glycemia, and associated endothelial dysfunction, by maternal diabetes subtype. METHODS/STUDY POPULATION: Pregnancies with maternal Type 1 (T1DM), Type 2 (T2DM), and gestational diabetes mellitus (GDM) are being enrolled. Maternal hemoglobin A1c (HbA1c) and umbilical cord insulin/glucose are being collected from 20 pregnancies in each group, 10 of which also undergo placental/umbilical cord tissue collection. Following delivery, neonatal blood glucose levels are also collected every 3-4 hours (4+ measurements) to determine rate of glycemic change. Linear regression modeling will be used to determine associations with placental and umbilical endothelial RNA expression, umbilical cord insulin levels, and maternal HbA1c within each diabetic subtype and between normoglycemic and hypoglycemic neonates. Endothelial gene expression will be compared using paired t-tests with Benjamini-Hochberg correction. RESULTS/ANTICIPATED RESULTS: Thus far, 5 T1DM, 10 T2DM, and 13 GDM samples have been collected. Gestational age at delivery and birth weight were similar between groups (38.1 ± 1.05 weeks; 3.6 ± 0.59 kilograms) and delivery method is evenly distributed (Cesarean section or vaginal delivery). Currently, with limited cohort size, no association is evident between maternal HbA1c and umbilical cord glucose/insulin (p=0.114) or neonatal hypoglycemia diagnosis (p=0.674) when controlled for gestational age and infant birthweight. We hypothesize that, with pending analyses, maternal HbA1c and umbilical cord insulin levels will correlate negatively with the rate of neonatal glycemic change, and positively with the level of inflammatory and angiogenic transcription identified in placental and umbilical endothelium. DISCUSSION/SIGNIFICANCE: Characterization of postnatal glucose control is key to prognosis and risk stratification of infants of diabetic mothers. Understanding placental response to glucose, as well as sequela in the fetal endothelium, is also critical to understanding the pathogenesis of neonatal hypoglycemia and other adverse outcomes of diabetic pregnancy.

ABSTRACT IMPACT: Understanding dietary patterns and nutrient intakes of the aging population may help address concerns and dietary guidelines regarding their nutritional needs. OBJECTIVES/GOALS: The objective of this study is to test the hypothesis that a healthy dietary pattern in the oldest old (aged 80 years and older) is related to greater compliance with dietary recommendations and better nutrient intake profiles. METHODS/STUDY POPULATION: We conducted a cross-sectional study of 122 participants aged 82 to 97 years old from the Geisinger Rural Aging Study (GRAS) cohort in rural Pennsylvania (n = 56 men and 66 women). The main outcome measures of the investigation were the daily nutrient intakes and food group intakes evaluated from the average of three 24-hour dietary recalls. The dietary patterns were determined by cluster analysis from 28 food groups. Diet quality and adherence to the Dietary Guidelines for Americans was assessed by the Healthy Eating Index (HEI)-2015 and the Dietary Screening Tool (DST). Recommended intakes were determined by the Recommended Dietary Allowances (RDAs) or Adequate Intakes (AIs). RESULTS/ANTICIPATED RESULTS: Less than 50% of participants met the dietary recommended intakes for vitamins D, E, K, B6, dietary fiber, zinc, potassium, and calcium. The more-nutrient-dense cluster was characterized by higher intakes of fruits and vegetables. The less-nutrient-dense cluster was characterized by higher intakes of foods including desserts and sweets. After adjusting for age, sex, and energy intake, participants in the more-nutrient-dense dietary pattern had a higher intake of vitamins A, D, K, C, fiber, and potassium (p < 0.05 for all). After adjusting for age and sex, participants in the more-nutrient-dense pattern had better diet quality assessed by the (HEI)-2015 (p < 0.001) and DST (p = 0.006). DISCUSSION/SIGNIFICANCE OF FINDINGS: Among the oldest old, many participants were found to have nutrient intakes lower than the recommended levels for fundamental nutrients suggesting that dietary guidance in addition to a dietary pattern more aligned with dietary guidelines may be beneficial for supporting healthy aging.

OBJECTIVES/SPECIFIC AIMS: Treatment of breast cancer surgery can be classified into two overall groups: Breast-Conserving Therapy (BCT) (including partial mastectomy (PM) and oncoplastic surgery (OS)) and MAST (including mastectomy (M) and M with breast reconstruction (M+R)). Breast reconstruction (OS or M+R) offers patients an improved quality of life by aesthetically symmetric breast, higher patient satisfaction and reduced re-excision rates. Furthermore, subgroups of M+R, mastectomy with implant placement (M+I) has doubled to 21%, meanwhile mastectomy with muscular flap reconstruction (M+MF) has declined to only 2% of overall breast cancer intervention. Furthermore, in patients with with ductal carcinoma in situ (DCIS), published national guidelines recommend that sentinel lymph node biopsy (SLNB) should be offered when treated with M and should not be offered when treated with BCS. Overall complication rates for breast cancer surgery vary depending on short-term or long term outcome but are approximately 2-40%. Mortality and overall morbidity are overall low in less than 5% of cases. Known wound or infectious complications have been associated with smoking, radiation, obesity and diabetes. Nevertheless, other patient comorbidities and surgical predictors influencing acute postoperative complications are contentious. Single institutional studies or reviews compared single or two groups of breast cancer interventions for post-operative complication rates. Few studies with large enough patient cohort to analyze all possible variables influencing post-operative acute complications following all breast cancer surgeries. Understanding surgical complications is crucial to patient safety and improving health outcomes. Therefore, this study examines the 30-day postoperative complication rates in breast cancer patients who underwent a PM, M, M+R, or OS. Using the NSQIP database, we aim to elucidate these surgical trends and complications trends, while expanding our understanding of predictive surgical factors. We also examined appropriate axillary management associated with surgical interventions between 2005 and 2016. METHODS/STUDY POPULATION: A retrospective cohort analysis was conducted using the ACS-NSQIP database from 2005 to 2017. All participant user files (PUF) were obtained and approved by ACS NSQIP. The Tufts Medical Center Institutional Review Board deemed this study exempt from institutional review, given ACS NSQIP database is a de-identified data set. Inclusion criteria for this study were women with classified post-operative diagnosis of invasive breast cancer (IBC) or ductal carcinoma in-situ (DCIS) breast cancer who underwent either any BCT or any MAST procedure. Post-operative diagnosis was classified according International Classification of Diseases Ninth/Tenth Revision (ICD-9/10) code for IBC or DCIS. Surgical (M, PM, OS, M+R) and axillary lymph node categorization were done using CPT codes known for each intervention. Exclusion criteria included males, benign breast surgery, surgery for benign breast disease, lobular carcinoma, patients undergoing breast cancer surgery with 2 CPT codes with ambiguous category placement and septic patients at time of surgery. For each intervention, a total of 16 complications were clustered into 8 groups and examined over the 13-year period. ALN management was categorized as follows: no intervention on ALNs, or ALN surgery (SLNB or ALN dissection (ALND)). Chi-square tests were performed for demographic and complication rate analysis. Smoothed linear regression and non-parametric Mann- Kendall test assessed complication trends. Uni-variate and multivariate logistical regression were computed to associate odd’s ratio for comorbidities, surgical predictors and patients demographics. RESULTS/ANTICIPATED RESULTS: A total of 226,899 patients met the inclusion criteria. Annual breast surgery trends changed as follows: PM 45.6% to 45.9 (p=0.21), M 36.8% to 25.5% (p=0.001), M+R 15.7% to 23.6% (p=0.03) and OS 1.8% to 5.0% (p=0.001). Analyzing the patient cohort who underwent breast conservation, categorical analysis showed a decreased use of PM alone (96% to 90%) with an increased use of OS (4% to 10%). For the patient cohort undergoing mastectomy, M alone decreased (69% to 52%); M+R with muscular flap decreased (9% to 2%); and M+R with implant placement increased (20% to 41%) – all 3 trends p<0.0001. The rate of ALN management has changed as follows: SNLB or ALND significantly increased in mastectomy patients from 53.6% to 69.5% (SS 1.5%, R2 0.69, p < 0.01), while it changed little in the BCS population: 22.5% to 26.4% (SS 0.4%, R2 0.18, p = 0.09). Complication rates have steadily increased in all mastectomy groups (p< 0.05) but not in BCT. Cumulative complication rates between surgical categories were significantly different in each complication cluster (all p<0.0001). Overall complication rates were: PM: 2.25%, OS: 3.2%, M: 6.56%, M+MF: 13.04% and M+I: 5.68%. The most common predictive risk factors were mastectomy interventions, increasing operative time, ASA class and BMI, smoking, recent weight loss, history of CHF, COPD and bleeding disorders (all p<0.001). Patients who were non-diabetic, younger (<60) and treated as outpatient all had protective OR for an acute complication (p<0.0001). DISCUSSION/SIGNIFICANCE OF IMPACT: The modern era of breast surgery is identified by the increasing use of reconstruction for patients undergoing breast conservation (in the form of OS) and mastectomy (in the form of M+R). Despite national recommendations for the management of axillary lymph nodes in patients undergoing breast surgery for DCIS, nearly 30% of cases continue to be mismanaged: more than 30% of patients with DCIS undergoing mastectomy fail to receive SLNB, and more than 26% of DCIS patients undergoing BCS are still receiving axillary lymph node surgery. Our study provides data showing significant trends that will impact the future of both breast cancer surgery and breast training programs. We also provide data comparing nationwide acute complication rates following different breast cancer surgeries that can be used to inform patients during surgical decision making.

Effective community engagement in T3–T4 research is widespread, however, similar stakeholder involvement is missing in T1–T2 research. As part of an effort to embed community stakeholders in T1–T2 research, an academic community partnered team conducted discussion groups with researchers to assess perspectives on (1) barriers/challenges to including community stakeholders in basic science, (2) skills/training required for stakeholders and researchers, and (3) potential benefits of these activities. Engaging community in basic science research was perceived as challenging but with exciting potential to incorporate “real-life” community health priorities into basic research, resulting in a new full-spectrum translational research model.

Educational opportunities for investigators and staff to promote inclusive research practices are a critical piece of the effort to increase diversity in study participation and promote health equity. However, few trainings to date have empirically been shown to result in behavior changes. We present preliminary evaluation findings for the Just Research workshop offered at the University of Wisconsin–Madison between October 2022 and August 2023. These sessions included 80 participants who made up 4 cohorts. Data was collected through a retrospective pre/post-test survey administered 0–7 days following the workshop (n = 70), and a follow-up survey administered 9–12 months following the workshop (n = 21). Participants demonstrate significant increases in knowledge and self-efficacy regarding implementing inclusive practices post-intervention (p < .001). 85.7% of participants who completed the follow-up survey reported implementing inclusive practices.

OBJECTIVES/SPECIFIC AIMS: To evaluate gaps in knowledge for women who are cancer survivors regarding the impact of comorbidities and lifestyle behaviors on endometrial and cervical cancer risk, and to assess prevalence of established care with a primary care physician (PCP) among patients and evaluate acceptability of referral to a PCP METHODS/STUDY POPULATION: Single institution cross-sectional study examining all women aged 18 or older with a diagnosis of cervical or endometrial cancer who present for care by a gynecologic oncologist at Barnes-Jewish Hospital/Washington University in St. Louis School of Medicine. Patients will be invited to complete a survey specific to cancer diagnosis that includes questions on participant background and sociodemographic information, knowledge of risk factors for their specific cancer site, and whether or not the patient has a primary care provider and the acceptability of referring RESULTS/ANTICIPATED RESULTS: Majority of women will be unaware of how comorbidities affect cancer risk and treatment outcomes. For women without a PCP, we anticipate that they will be accepting towards the notion of being referred to one for establishing care. DISCUSSION/SIGNIFICANCE OF IMPACT: Pilot information from this study will 1. Allow providers to improve cancer survivorship care plans by increasing collaboration between PCPs and oncologists to provide ongoing care, and 2. Afford information for providers on where gaps in knowledge exist so as to better education patients.

OBJECTIVES/GOALS: Decision-making impairments in addiction can arise from dysfunction in distinct neural circuits. Such processes can be dissociated by measuring complex, computationally distinct behaviors within an economic framework. We aim to characterize computational changes conserved across models of addiction. METHODS/STUDY POPULATION: We used neuroeconomic tasks capable of dissociating neurally separable decision processes using behavioral analyses equally applicable to humans and rodents. We tested 12 human cocaine-users and 9 healthy controls on the Web-Surf task designed to match the rodent Restaurant Row task on which 27 mice were trained and then exposed to saline (n = 10), cocaine (n = 7), or morphine (n = 10). All subjects foraged for rewards (humans: entertaining videos; mice: food) of varying costs (1-30s delays) and subjective value (humans: genres; mice: flavors) by making serial accept or reject decisions while on a limited time budget, balancing the utility of wanting desirable rewards despite conflicting costs. RESULTS/ANTICIPATED RESULTS: When encountering unique offers for rewards with a delay above one’s willingness to wait, cocaine-treated mice like cocaine-exposed humans were less likely to appropriately reject economically disadvantageous offers. Furthermore, these mice and humans did so despite spending more time deliberating between future options. In contrast, morphine-treated mice displayed distinct impairments when given the opportunity to correct past mistakes, a process we previously demonstrated was uniquely sensitive to alterations in strength of synaptic connectivity of the infralimbic-accumbens shell circuit in mice. We anticipate human opioid-users will mirror these latter, computationally distinct findings. DISCUSSION/SIGNIFICANCE OF IMPACT: These data elucidate facets of addiction shared across species yet fundamentally distinct between disease subtypes. Our translational approach can help shed light on conserved pathophysiological mechanisms in order to identify novel diagnostic parameters and computational targets for intervention.

ABSTRACT IMPACT: This research study will provide evidence for public policy, systemic changes, and other interventions to address the adverse impacts of prolonged stress exposure experienced by young Black men. OBJECTIVES/GOALS: Previous studies have demonstrated a strong association between allostatic load (i.e., stress-induced cumulative biological risk) and mortality in the Black American population. The aim of this study is to examine the association between allostatic load and mortality in Black men and to determine if the relation varies by age. METHODS/STUDY POPULATION: Data from the third National Health and Nutritional Examination Survey (NHANES III, 1988-1994), linked to the 2015 National Death Index Public Release File, will be used for Black male adults 18 years or older. Allostatic load score includes nine biomarkers: albumin, C-reactive protein, total cholesterol, high-density lipoprotein, hemoglobin A1C, waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, and pulse rate. The number of variables for which the participant’s scores fall in the quartile of highest clinical risk are added together to create a summary score. Cox proportional-hazard analyses is employed to estimate the associations between allostatic load and all-cause mortality for the total sample and stratified by age, adjusting for selected characteristics. RESULTS/ANTICIPATED RESULTS: We hypothesize that the association of allostatic load with mortality will be greater among younger, compared to older, Black men. Young Black men (ages 25-44) are at particular risk of adverse impacts of chronic stress and allostatic load, due to their experience of chronic discrimination, systemic racism, racial battle fatigue, and mundane, extreme, environmental stress. Furthermore, the allostatic load-mortality association may be attenuated for older Black men due to a survival effect. DISCUSSION/SIGNIFICANCE OF FINDINGS: If the association between allostatic load score and mortality is stronger in young Black men, it would provide evidence for early identification of a group with high risk of premature mortality, and for public policy, systemic changes, and other interventions to address the adverse impacts of prolonged stress exposure experienced by young Black men.

OBJECTIVES/GOALS: Peri-implantitis is the inflammation of peri-implant mucosa and subsequent loss of supporting bone. Its treatment is only <40% successful mainly due to persistent bacterial infection. The goal of this project is to increase success rates by developing a robust antibiofilm multi-biomolecular membrane that can be placed around implant surfaces. METHODS/STUDY POPULATION: A collagen membrane was soaked in the antimicrobial peptide GL13K solution overnight to form an interpenetrating fibrillary network. The nanostructure of the membrane was imaged with scanning electron microscope (SEM). The hydrophobicity of the membrane was analyzed by water contact angle (WCA) measurements. The biodegradability was tested in a 0.01 mg/mL Type I collagenase solution for up to 5 weeks. The antimicrobial activity of the membrane was assessed with Gram-positive oral bacteria Streptococcus gordonii. The cytotoxicity was evaluated by culturing human gingival fibroblasts (HGF), and the osteogenesis was assessed using preosteoblasts MC3T3. Pure collagen membrane was used as the control. Statistical significance (p<0.05) was determined by one-way ANOVA with Tukey’s HSD test. RESULTS/ANTICIPATED RESULTS: The antimicrobial peptide GL13K self-assembled to short fibrils (< 1 µm long), which entangled with the larger collagen fibers (around 200 nm in diameter). The collagen fibers presented characteristic periodic banding structures, which provided biomimetic cues for cell behavior as extracellular matrix. The interpenetrated GL13K fibrils turned the highly hydrophilic collagen membrane to a hydrophobic membrane (WCA = 135 °) and significantly reduced the rate of degradation by collagenases. The developed membrane was efficient in preventing the attachment of S. gordonii. A large portion of the attached bacteria was killed on the surface of the membrane. The incorporation of GL13K did not affect the cytocompatibility of the membrane for HGF. DISCUSSION/SIGNIFICANCE OF IMPACT: We developed an antibiofilm membrane with interpenetrating collagen and antimicrobial peptide fibrils. The strong antimicrobial activity and low cytotoxicity support its further translational evaluation as scaffolds for increasing success rate in treating peri-implantitis.