We used Cerner Real-World Data™, representing hospital admission records from 2020, to examine patients with co-occurring sickle cell disease and COVID-19 by discharge disposition grouped as death/hospice versus transfers to other facilities, returned home, or left against medical advice. Among the death/hospice group, we found older age and higher rates of congestive heart failure and diabetes. There were also significant differences in tachypnea, mechanical ventilation, minimum O2 saturation, and length of stay with higher rates in the death/hospice group. Awareness of such factors and associated mortality risks for this population may aid in patient care.

OBJECTIVES/SPECIFIC AIMS: Identify objective neurological substrates of cognitive fatigue in Parkinson’s disease and in aging. METHODS/STUDY POPULATION: Structural and diffusion MRI. Behavioral assessments for aged adults and Parkinson’s disease. RESULTS/ANTICIPATED RESULTS: Gray and white matter deficits that correlate with deficits in the basal ganglia for fatigued Parkinson’s disease patients Versus anterior cingulate cortex in healthy aged adults with fatigue. DISCUSSION/SIGNIFICANCE OF IMPACT: Over 50% of patients with Parkison’s disease and 38% of healthy older adults suffer from cognitive fatigue. However, diagnostics are limited to subjective surveys and there are no treatments for either population. Therefore, objective measures are greatly needed for better diagnosis and development of treatment targets.

Long-term sequelae of severe acute respiratory coronavirus-2 (SARS-CoV-2) infection may include increased incidence of diabetes. Here we describe the temporal relationship between new type 2 diabetes and SARS-CoV-2 infection in a nationwide database. We found that while the proportion of newly diagnosed type 2 diabetes increased during the acute period of SARS-CoV-2 infection, the mean proportion of new diabetes cases in the 6 months post-infection was about 83% lower than the 6 months preinfection. These results underscore the need for further investigation to understand the timing of new diabetes after COVID-19, etiology, screening, and treatment strategies.

OBJECTIVES/GOALS: Septic shock is a lethal condition. Research suggests that overall sepsis mortality varies by race, but less is known about demographic differences in septic shock mortality. Our objectives were to describe the septic shock population using a large, state-wide data repository and identify demographic predictors of septic shock mortality. METHODS/STUDY POPULATION: This was a retrospective review of patients with septic shock in the One Florida Data Trust from 2012-2018. Patients were classified as having septic shock if they received vasopressors and had either 1) an ICD-9 or 10 code for septic shock or 2) an ICD-9 or 10 code for infection and an ICD-9 or 10 code for organ dysfunction. Demographic data and place of residence prior to admission was collected. The primary outcome was 90 day mortality. T-test and chi-square tests were used to test association of individual predictors and mortality. Multiple logistic regression was used to identify predictors of mortality after adjustment for other variables. Level of significance was set at 0.05. SAS v9.4 (Cary, NC) was used for analyses. RESULTS/ANTICIPATED RESULTS: There were 11,790 patients with septic shock. The mean(SD) age was 61(16) years. With regard to race/ethnicity 66% identified as white, 27% as black, 3.7% as Hispanic, and 3.5% as other races (non-white, non-black, non-Hispanic). Most came from home (57%). Overall, 39% died. Mortality varied by race (p<0.01): white 39%, black 39%, Hispanic 31%, other races 51%. In the logistic regression model, age, race, and residence were significant predictors of mortality, after adjustment for other variables. Each additional year of age had a 2.7% increased odds of mortality (OR 1.03; 95% CI 1.02-1.03; p<0.01). Compared to white patients, odds of death were 1.6 times higher for other races (95% CI 1.3-2.0; p <0.01) and non-significantly higher for black patients (OR 1.1; 95% CI 1.0-1.2; p = 0.05). Compared to those from home, odds of death were highest for those from a skilled nursing facility (OR 1.5; p<0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: Patients who identified as other races had increased mortality from septic shock compared to white patients after adjusting for other variables. Septic shock mortality also increased with age and varied by residence. Further analyses are needed to examine racial disparities and control for comorbidities, severity of illness, and aspects of resuscitation. CONFLICT OF INTEREST DESCRIPTION: The authors report no conflicts of interest, except for Dr. Fernandez, who reports personal payment from Physio-Control, Inc. for speaker fees.

OBJECTIVES/GOALS: The major objective of this project is two points. First, is to repeat and confirm previous observations that there is elevated cytosolic Line1 DNA in the cytoplasm of cells derived from old mice compared to young. Second is to identify which Line1s in the genome are contributing to this free DNA and test if targeting them rescues the age-related phenotype. METHODS/STUDY POPULATION: This project will focus on data collected from both tissues and primary cells derived from multiple tissues. Using cellular/tissue fractionation kits, we isolate specifically from the cytoplasm. This specificity is confirmed by western blotting. Measurement of the Line1 levels is measured by quantitative PCR. Subsequently, these cytoplasmic samples are sent off for sequencing in order to quantify the length of the free DNA in the cytoplasm and to identify which Line1 genomic families the cytosolic DNA originates. Additionally, FISH is utilized to visualize Line1 DNA in the cytoplasm of aged versus young cells RESULTS/ANTICIPATED RESULTS: We anticipate this research to confirm the hypothesis that extranuclear Line1 DNA accumulates with age in both tissues and primary fibroblasts. Additionally, we expect to be able to determine which specific families of genomic Line1 is driving this extranuclear DNA, which would suggest the active retrotransopable elements that are directly involved in this aging related phenotype. Assuming successful identification of such families, we can then target and silence these specific elements to determine not only if cytoplasmic Line1 in aged mice decreases, but additionally if the healthspan and/or lifespan of these mice improves DISCUSSION/SIGNIFICANCE: Dereoressed Line1s have been shown to be involved in detrimental phenotypes, including autoimmune disease, cancer, and inflammaging. Targeting retrotransposons, either directly through degradation of transcriptional product of LINE1s or indirectly by improving function of regulators, will be crucial in ablating aging phenotypes

OBJECTIVES/GOALS: Understanding the mechanism of transcriptional adaptation may contribute to an explanation for variation in clinical manifestations of Amyotrophic lateral sclerosis patient phenotypes. METHODS/STUDY POPULATION: To examine transcriptional adaptation, we utilized gene editing tools in HT1080 cells and patient samples with known CHCHD10 mutations causative for Amyotrophic lateral sclerosis. Frameshift mutations were performed via CRISPR-Cas9. Ribonucleoprotein electroporation was used to transfect cells and DNA sequencing was conducted to validate gene editing. To validate transcriptional adaption, changes in levels of protein and gene expression will be measured via immunoblot and quantification of CHCHD10 and CHCHCD2 from whole cells lysates of the edited cells. RESULTS/ANTICIPATED RESULTS: We anticipate that CHCHD2 transcriptional adaptation can functionally compensate for the locus loss of function of CHCHD10. This mechanism of transcriptional adaptation may contribute to an explanation for variation in clinical manifestations of patient phenotypes. DISCUSSION/SIGNIFICANCE: Our approach would advance discovery science towards by exploring CHCHD10/2 transcriptional adaptation mechanism that can lead to novel therapies for rare Amyotrophic lateral sclerosis, such as CHCHD10-R15L.

OBJECTIVES/SPECIFIC AIMS: Objective: To summarize the diagnosis and management of two acute rejection (AR) episodes in the first penis transplant patient in the U.S. Background: Vascularized composite allotransplantation (VCA) has been utilized for state-of-the-art reconstruction of devastating craniofacial defects, limb loss, and recently, severe genitourinary defects. To date, more than 200 VCA’s have been performed, of which four successful penis transplants have been achieved worldwide (Two in the U.S.). However, despite the technical success of VCAs in general, acute rejection episodes remain a significant postoperative management problem, with 80-85% experiencing at least one episode in the first-year post-transplantation. The incorporation of skin in VCAs, which is highly immunogenic, allows early visible recognition of rejection but requires prompt management to prevent allograft failure as well as the progression of chronic rejection, which has been associated with the frequency of acute rejection episodes in preclinical models. We present the first report of acute rejection in a penile allograft. AR episodes in VCA typically manifest with erythema of the allograft skin and/or maculopapular lesions that can be either patchy, focal or diffuse. Histopathologic assessment is essential for diagnosis and management. The Banff classification of histopathologic criteria for degree of AR is most commonly utilized to direct clinical management. METHODS/STUDY POPULATION: We reviewed the clinical course of the first American patient who underwent penis transplantation at Massachusetts General Hospital in 2016. Postoperatively, routine clinical and chemical assessment (immunosuppression levels, routine blood work) was performed, with increased frequency during AR episodes. Skin punch biopsies were obtained during (suspected) AR episodes, analyzed and graded according to the Banff 2007 classification of rejection of skin-containing composite allografts. Histopathologic tissue assessment included CD3, C4d, CD4/8, CD20 FOXP3 and cellular infiltration (hyper keratinization, lymphocytic infiltrate, dermal erosion, macrophage, eosinophilia, T-cell infiltration) and epidermal or perivascular fibrosis. RESULTS/ANTICIPATED RESULTS: The patient is a 65-year-old male with history of penile carcinoma requiring subtotal penectomy in 2012. He is currently 30-months post penile transplantation (as of 11/15/2018). First Rejection Episode: At 28 days post-transplantation, the patient noted induration, swelling and erythema of the allograft, which was diagnosed as AR clinically (Image 1A). Biopsy showed a Banff Grade III AR, with focal keratinocyte apoptosis with lymphocytic infiltration in epidermis and arteriolar endothelialitis with perivascular inflammation. Initially this episode was treated for 2 days with 2 pulse doses of methylprednisolone (500mg/d IV) with clinical improvement. However, recurrent allograft erythema was observed on postoperative day 32 and an acute rejection grade III according the Banff classification was confirmed by a second biopsy that demonstrated epidermal perivascular lymphocytic infiltrates, spongiosis and dyskeratosis, deep dermis focal lymphocytic infiltrates and focal infiltrates in arterioles as well as endothelialitis in venules. Donor specific antibodies and C4d were negative. CD3+ T cells were present in the epidermis and perivascular space. This was treated with anti-thymocyte globulin (thymoglobulin) course for 4 days (1.5mg/kg/day IV) and 3 more pulse doses of methylprednisolone (500mg/d IV.), followed by a prednisone (250mg/d) taper to baseline. This resulted in complete resolution of AR. Second Rejection Episode: At 10.8 months post VCA the patient presented with penile erythema and scrotal swelling suggestive of AR and received three doses of methylprednisolone (day 1: 500mg/d IV, day 2: 1000mg/d IV and day 3: 500mg/d IV respectively) followed by increased baseline prednisone (10mg PO daily; increased dose compared to previous AR episode). A skin biopsy confirmed Banff Grade III AR. Compared to the previous biopsy, this biopsy demonstrated an increased density of lymphocytic inflammation of the dermis with endarteritis. Prominent involvement of epidermis and adnexal structures corresponding to acute T-cell mediated rejection was also observed (Figure 1). Donor specific antibodies and C4d were again negative. Three doses of ATG (1.5mg/kg/day IV) were administered. In addition, tacrolimus was increased and local tacrolimus (1% ointment) treatment was begun. Clinical signs of rejection improved and repeat biopsy showed dramatic histopathological improvement. Current maintenance immunosuppressive regimen consists of tacrolimus, sirolimus, prednisone, mycophenolic mofetil acid (MMF), rapamycin, and tacrolimus ointment, with no new clinical or histopathological signs of rejection (Image 1B). DISCUSSION/SIGNIFICANCE OF IMPACT: We report the first described case of acute T-cell mediated rejection in penile transplantation. These rejection episodes demonstrated that, even on stringent immunosuppressive regimens, severe acute rejection episodes in VCA may still occur. Edema and acute induration preceded the development of erythema in our cases, representing a harbinger for the more severe grade of rejection that eventually developed. Our experience was consistent with other VCAs in that donor specific antibodies did not develop, despite a severe Banff Grade. Consistent use of topical calcineurin inhibitor based immunosuppression on the allograft skin may be helpful in warding off future episodes, as our patient has been rejection free now for 18 months. To date, no histologic signs of chronic rejection were present on 2-year protocol surveillance biopsy. We have added rapamycin to the current drug regimen, with concurrent reduction of tacrolimus dosing for renal protection, which has been demonstrated in cardiac transplantation to deter the intimal hyperplasia/vasculopathy associated with chronic rejection.

OBJECTIVES/SPECIFIC AIMS: Because clinical trial results are instrumental in the approval of a new drug or changes to the practice of medicine, ensuring the accuracy and validity of collected data is critical in the clinical trial process. This function, routinely carried out by clinical trial monitors in industry-sponsored trials, is often lacking in investigator-initiated trials (IITs) conducted in academia. To address this challenge, we have developed a self-study module that can be used to cross-train academic researchers in essential concepts and practical approaches to monitoring. Furthermore, we are applying a framework drawn from implementation science in the development and launch of this initiative. This framework, as used in other educational programs, is employed here to close the gap between initiative and practice, thereby effectively disseminating this training would improve the quality of clinical trials in academia. METHODS/STUDY POPULATION: This research project applied exploration, installation and implementation stages of the implementation science process by 1) exploring the need for a new initiative, 2) disseminating results, 3) engaging stakeholders, 4) creating standard operating procedures (SOPs) for installation and implementation, 5) studying user satisfaction and effectiveness, 6) addressing feedback and 7) conducting implementation. RESULTS/ANTICIPATED RESULTS: From literature review and internet searches we determined that although numerous GCP training resources exist, most are too broad and lack the practical approaches to meet the complex requirements of monitoring. Moreover, most of the offerings identified are costly or inaccessible. With only about 65% of IITs reported as being monitored (Figures 1 and 2), it appears that there is a clear need for training tools that are easily available to a broader audience. And because monitoring skills are substantially different from those associated with research coordination, it is not surprising that research professionals believed that they would need additional training to become proficient. To address this need, we began developing a monitoring module. We engaged key stakeholders from academia and industry to gain insights into their needs. The results indicated that although our training module was effective, supplementary information on the fundamentals of clinical trials should be included for those new to the field. After incorporating suggested changes and completing the module, we conducted user testing to determine if our module is ready to be broadly disseminated (Figures 3 and 4). Following positive feedback from the group, we are currently in the process of disseminating our module and studying its impact. DISCUSSION/SIGNIFICANCE OF IMPACT: IITs are instrumental in translating academic research into product development. Deficiencies in the quality control of these trials can lead to inadequacies in data accuracy and validity that could lead to significant delays in bringing innovative therapies to patients. Recent NIH policies require data and safety monitoring for all of the trials it supports. The latest addendum to ICH GCP, E6(R2), discusses a need for quality management across the clinical trial lifecycle. As we continue to disseminate and share information during the development of our self-study monitoring module, we are engaging key stakeholders from academia, government, and private institutions to understand and address quality challenges in conducting clinical trials. Finally, this research informs dissemination and implementation research, specifically for creating training for academic research professionals.

OBJECTIVES/GOALS: Pilot grants are small financial investments given out by CTSA hubs to facilitate new clinical and translational research projects. The New Jersey Alliance of Clinical and Translational Science (NJ ACTS) is one of 65 CTSA hubs. The goal of this project was to evaluate and improve the NJ ACTS program by learning from pilot programs across the consortium. METHODS/STUDY POPULATION: The initial research on pilot programs was conducted using the CTSA Search Solutions tool, a tool developed at NJ ACTS which provides links to individual pages by topic in all the hub websites. Using the tool, public information was accessed, including common award amounts, significant dates, and preferred categories of research. Then, a survey created in REDCap was distributed to colleagues at all CTSA hubs to gather additional information and thoughts on pilot programs. The data were compiled in an excel database to observe and analyze trends. These trends were graphically presented in figures developed from the data to see how NJ ACTS compares to other CTSA hubs in how they focus and operate their pilot programs. RESULTS/ANTICIPATED RESULTS: There are both similarities and differences between NJ ACTS and other hubs. NJ ACTS utilizes a REDCap form for its application, as do 14 other CTSA hubs. Surveys also show that NJ ACTS follows similar processes for: letter of intent and application due dates; having a standing review committee; and the categories of awards. Award categories for Clinical/Translational Innovation, Methodology/Infrastructure, and Partnership/Collaboration are shared with 47, 25, and 41 institutions, respectively. NJ ACTS requires collaboration between its multiple institutions, as do 28 other hubs. It does not, however, have a public notification of award date, and notifications tend to go out relatively late. NJ ACTS funded multiple proposals pertaining to COVID-19, something 11 other CTSA hubs did as well. DISCUSSION/SIGNIFICANCE: Although a new CTSA hub, NJ ACTSs Pilot Program operates comparably to more mature CTSA hubs. Using the survey data, NJ ACTS can implement modest changes, better serving its scientific community. CTSA Search Solutions has proven an excellent tool and can be used by any hub to understand how they compare and implement changes to improve their programs.

OBJECTIVES/SPECIFIC AIMS: We aim to leverage our analysis of the scientific collaboration network at a research university to design an innovative pilot program and foster scientific productivity. We test the impact of creating a new collaboration in a research community, which decreases the average network distance and accelerates the diffusion of information and expertise among the community’s investigators. METHODS/STUDY POPULATION: We mapped the whole network of co-authorship on publications and co-participation on extramurally awarded grants at the University of Florida (UF) between 2013 and 2015. We used network science methods to identify research communities of investigators who have consistently worked together and/or have other collaborators in common with at least one researcher based in the UF Health Science Center. We selected pairs of communities with (i) similar productivity levels, research interests, and network structures and (ii) no research projects in common. Communities in each pair were randomly assigned to a treatment or control group. In each treatment community, we selected 1 pair of investigators who had not collaborated in the past 3 years and whose connection would maximally reduce average network distance in the community. The pair was provided with an economic incentive to collaborate for the submission of a CTSA pilot proposal. RESULTS/ANTICIPATED RESULTS: We successfully identified 15 pairs of treatment/control communities. In each of 8 treatment communities, a pair of potential collaborators agreed to participate in the intervention. DISCUSSION/SIGNIFICANCE OF IMPACT: Network-informed Clinical Translational Science Awards (CTSA) pilot programs can identify research communities and create innovative collaborations. Statistical experiments can establish the programs’ causal effects on scientific productivity.

OBJECTIVES/SPECIFIC AIMS: This study aims to understand the factors influencing engagement with out-patient services from pregnancy to 1 year postpartum among women in recovery from opioid use disorders (OUD). METHODS/STUDY POPULATION: We conducted semi-structured qualitative interviews and a brief survey with 20 mothers in OUD recovery recruited from health care and community organizations in Western MA. Transcripts were coded by two independent coders and analyzed using a qualitative descriptive approach. RESULTS/ANTICIPATED RESULTS: The average duration of any addiction treatment among the 20 participants was 5.6 years with 80% receiving medication-assisted treatment during a pregnancy. Approximately two-thirds experienced relapse during pregnancy or the first year postpartum. We identified 3 themes elucidating women’s experiences around service engagement: “How I see myself” (personal development), “How services see me” (service delivery quality), and “Are you with me?” Personal development included response to past trauma, coping strategies and self-advocacy, and adjusting to parenthood. Service delivery quality was influenced by service design, efficacy of individual providers, and cultural norms (organizational and societal). In the final theme, intersection of individual and service-level factors influenced the degree and quality of the women’s experience engaging with services. DISCUSSION/SIGNIFICANCE OF IMPACT: Women describe successful engagement when they experience service providers as being emotionally supportive, delivering relevant services, and advocating on their behalf. To best support and engage families affected by OUD, relevant and timely services should be linked with compassionate delivery.

OBJECTIVES/SPECIFIC AIMS: This study aims to assess the safety, feasibility, clinical benefits and pharmacodynamics of adding allopurinol to standard maintenance therapy that includes 6-mecaptopurine (6-MP) in pediatric patients with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma. Our goal is to investigate if allopurinol improves hepatotoxicity and GI toxicity, if it safely decreases acute neutrophil count (ANC), if it reduces the 6-MP dose required during chemotherapy, and if it works through our hypothesized mechanism by lowering the levels of the toxic metabolite, 6-methylmecaptopurine (6-MMP) and by raising the levels of the active metabolite, 6-thioguanine (6-TGN). METHODS/STUDY POPULATION: This is a single arm, nonblinded pilot study of patients under age 30 years who were being treated in the maintenance phase of therapy for ALL or lymphoblastic lymphoma, and had adverse effects such as high 6-MMP:6-TGN ratio, high ANC, and high liver enzymes. Patients enrolled were started with allopurinol in addition to ongoing oral chemotherapy. Data from beginning maintenance to end of chemotherapy was collected in the electronic medical record, EPIC for the 13 patients enrolled at Johns Hopkins, and data analysis was conducted using STATA and Excel. RESULTS/ANTICIPATED RESULTS: Initial data analysis reveals that the required dose of 6-MP after addition of allopurinol to the chemotherapy regimen was significantly lower compared with that before the addition of allopurinol in 11 out of the 12 patients assessed (p<0.05). Among the 10 patients that were assessed for 6MMP:6TG ratio, all had lower average 6MMP:6TGN ratios after allopurinol compared to before allopurinol; the percentage of weeks that goal 6MMP:6TGN ratio (<40) were maintained were statistically significant in 6 patients (p<0.05) and close to significance in 2 other patients (p=0.057). The percentage of weeks that patients maintained alanine aminotransferase levels below 120 was significantly greater after addition of allopurinol compared to before the addition of allopurinol in 9 out of 13 patients assessed, suggesting that allopurinol may be associated with reduced hepatotoxicity. Further data analysis is ongoing to assess the percentage of weeks that patients maintained goal total bilirubin, direct bilirubin, and ANC, as well as average number of admissions for infections and average number of therapy holds after allopurinol addition compared to before allopurinol addition. DISCUSSION/SIGNIFICANCE OF IMPACT: Allopurinol is associated with reduction in required 6-MP dose, decrease in the percentage of weeks that patients have hepatotoxicity, and reduction in the ratio of toxic metabolite to active anti-leukemic metabolite in several patients. We hope that the results of this study can be used for further research and for guiding clinical practice since there are no established guidelines in pediatric oncology regarding addressing side effects of oral chemotherapy using 6-MP. If allopurinol indeed is safe and effective, adding it to the standard chemotherapy regimen can lead to better tolerance and compliance to oral maintenance chemotherapy, and hopefully improved outcomes for children with ALL and lymphoblastic leukemia.

OBJECTIVES/GOALS: Despite calls for the integration of Education for Sustainable Healthcare (ESH) into health professional training programs, most curricula have yet to adapt accordingly. This qualitative study sought to understand faculty perspectives on ESH knowledge, interest, barriers, and facilitators. METHODS/STUDY POPULATION: From 2018 to 2020, 71 health professional education faculty from 6 University of California (UC) campuses participated in ESH integration workshops. Using purposeful sampling based on gender and campus, a subset of workshop faculty participants were selected to participate in individual interviews. Interviews were conducted via Zoom using a structured interview guide, eliciting participants experience integrating ESH, perceived barriers and facilitators, and perspectives on student, faculty, and health science leadership knowledge and interest. Transcripts were double coded with an inductive-deductive approach using Dedoose, reconciled, and analyzed to identify themes. RESULTS/ANTICIPATED RESULTS: Participants included 17 faculty at 6 UC campuses representing diverse health disciplines. Although participants noted high general awareness of and interest in climate change among students and faculty, they observed a lack of specific, health-relevant knowledge, resulting in discomfort communicating with others on climate and health. Perceived barriers to expansion of ESH included limited curricular space, competing topics, and lack of faculty expertise. Participants posited that framing climate change in health terms, establishing learning objectives and protected faculty time, identifying connections to ESH within existing research and curriculum, and obtaining commitments from campus leadership would facilitate successful ESH integration. DISCUSSION/SIGNIFICANCE: Our findings reinforce student and faculty interest in ESH curricular integration and identify important barriers and facilitators, lending context for educators planning ESH infusion. Training of faculty on climate health is urgently needed for ESH integration in health professional education.

OBJECTIVES/GOALS: Research on the safety of perinatal kratom use - an herb that acts on opioid receptors - is scarce. Our transdisciplinary clinical and translational science (CTS) team is conducting parallel qualitative analyses of subreddit posts related to kratom use during (1) pregnancy and (2) breastfeeding. METHODS/STUDY POPULATION: Pregnancy- and breastfeeding-related keywords are being used to extract posts and selected metadata from the following subreddit communities: r/kratom, r/quittingkratom, r/pregnant, and/or r/breastfeeding. After the removal of duplicate posts, posts written in a non-English language and those that state in the post text and/or title that they were published by minors ( RESULTS/ANTICIPATED RESULTS: Among the eligible posts, the number of unique usernames of the sources publishing the posts; the range of publication dates; and the mean, median, & range of the number of comments per post will be presented. Inter-rater concordance in thematic coding will be computed. A word cloud will be created with the most used nouns from the eligible posts. Verbatim quotes will be shown to illustrate themes depicted in the sample. The quantitative and qualitative analyses will be conducted separately for the posts related to kratom use during pregnancy and breastfeeding. DISCUSSION/SIGNIFICANCE: These findings could assist clinicians in identifying questions that obstetric patients may have regarding the perinatal use of this emerging substance of concern. Further research is needed to validate these findings using other social media data, such as Twitter.

OBJECTIVES/SPECIFIC AIMS: MicroRNAs are small, non-coding RNAs that control gene expression by inhibiting protein translation. Preclinical studies in rodent stroke models suggest that changes in microRNA expression contribute to neural repair mechanisms. To our knowledge, no one has previously assessed microRNA changes during the recovery phase of human stroke. Our goal was to determine whether patients with significant upper limb recovery following stroke have alteration of neural repair-related microRNA expression when compared to those with poor recovery. METHODS/STUDY POPULATION: Plasma was collected at 19 days post-stroke from 27 participants with mild-moderate upper extremity impairment enrolled in the Critical Periods After Stroke Study. MicroRNA expression was assessed using TaqMan microRNA assays (Thermo Fisher Scientific). Good recovery was defined as ≥6 point change in the Action Research Arm Test (ARAT) score from baseline to 6 months. Bioinformatics analysis compared the plasma microRNA expression profiles of participants with good Versus poor recovery. Candidate biomarkers were identified after correcting for multiple comparisons using a false discovery rate <0.05. RESULTS/ANTICIPATED RESULTS: Eleven microRNAs had significantly altered expression in the good (n=22) Versus poor (n=5) recovery groups, with 2 showing increased expression—miR-371-3p and miR-520g, and 9 showing decreased expression—miR-449b, miR-519b, miR-581, miR-616, miR-892b, miR-941, miR-1179, miR-1292, and miR1296. Three of these could be implicated in neural repair mechanisms. Elevated miR-371-3p levels increase the likelihood that pluripotent stem cells will differentiate into neural progenitors. MiR-892b decreases levels of amyloid precursor protein, which has been implicated as a regulator of synapse formation. Finally miR-941, the only known human-specific microRNA, downregulates the CSPα protein which is involved in neurotransmitter release. DISCUSSION/SIGNIFICANCE OF IMPACT: This preliminary study suggests that circulating microRNAs in the plasma may help serve as biomarkers of neural repair and aid in understanding human neural repair mechanisms. If validated in larger studies with appropriate controls, these markers could aid in timing rehabilitation therapy or designing recovery-based therapeutics.

Storytelling is increasingly recognized as a culturally relevant, human-centered strategy and has been linked to improvements in health knowledge, behavior, and outcomes. The Community Engagement Program of the Johns Hopkins Institute for Clinical and Translational Research designed and implemented a storytelling training program as a potentially versatile approach to promote stakeholder engagement. Data collected from multiple sources, including participant ratings, responses to open-ended questions, and field notes, consistently pointed to high-level satisfaction and acceptability of the program. As a next step, the storytelling training process and its impact need to be further investigated.

Clinicians who are interested in becoming principal investigators struggle to find and complete training that adequately prepares them to conduct safe, well-designed clinical and translational research. Degree programs covering these skills require a significant time investment, while online trainings lack engagement and may not be specific to local research contexts. Staff at Tufts Clinical and Translational Science Institute sought to fill the gap in junior investigator training by designing an eight-module, noncredit certificate program to teach aspiring clinician-investigators about good clinical practice, clinical research processes, and federal and local regulatory requirements. The first iteration of this program was evaluated using pre- and posttest questionnaires and by gathering clinician learner feedback in a focus group. Based on the pre- and posttest questionnaires, learners experienced an increase in self-efficacy and confidence related to clinical research competencies. Feedback from learners also highlighted important program strengths, including an engaging program format, a manageable time commitment, and an emphasis on identifying crucial research resources. This article describes one approach to creating a meaningful and efficient clinical trial training program for clinicians.

OBJECTIVES/GOALS: Traumatic interpersonal experiences are associated with higher rates of chronic pain, increased pain severity and poorer functioning. The objective of this ongoing project is to obtain prevalence rates for various forms of interpersonal trauma among individuals with chronic pain, and to explore the potential mediating effect of heightened sensory and social sensitivity on the experience of pain. METHODS/STUDY POPULATION: Patients at Michigan Medicine between the ages of 18 and 65 complete an online survey. Patients are being recruited through a tertiary-care, outpatient pain clinic, as well as through an online health research portal. We aim to recruit 700 participants; we currently have 59.6% of our goal (n = 417). Participants also have the option to be included in a registry from which we can recruit for future studies. Approximately 85% of our participants have agreed to be in the registry. RESULTS/ANTICIPATED RESULTS: Preliminary data show that, of the 263 (63.4%) participants for whom data on chronic pain is available, 167 (63.5%) report chronic or persistent pain over the previous 3 months. Of these, 54% reported some form of childhood abuse or neglect. Approximately 41% reported four or more adverse childhood experiences. Additionally, of the 122 participants (73%) who were in a current romantic relationship, 20% reported some form of physical violence victimization from their romantic partner. We anticipate that interpersonal trauma will be associated with poorer perceptions of social relationships, higher sensory sensitivity, and higher perceived stress. DISCUSSION/SIGNIFICANCE OF IMPACT: The PASE Project parent study will be used to better understand prevalence rates for various forms of interpersonal trauma in our chronic pain population. Future analyses and studies will explore alternative pathways linking interpersonal trauma to the experience of pain through sensory and social sensitivity, which will inform interventions aimed at reducing pain among patients with a history of trauma.