OBJECTIVES/GOALS: The objective of this study is to synthetically generate and use records of exposure, and so that we can understand the effects of exposure on aging and vice-versa. METHODS/STUDY POPULATION: Quantifying bidirectional effects of environment and aging requires time series of data from all contributing exposures which can span endogenous processes within the body, biological responses of adaptation to environment, and socio-behavioral factors. Gaps in measured data may need to be filled with computationally modeled data. Essentially, the challenge in generating aging exposome is the absence of readily available records for individuals over the course of their life. Instead, these would need to be assimilated from historic person reported data (e.g. residential location, durations, behaviors) along with publically available data. This could lead to potential gaps and uncertainties that would need inform on how the exposomic records can be used for aging research. RESULTS/ANTICIPATED RESULTS: We present a pragmatic approach to generation of longitudinal exposomic and aging records as required for different study archetypes. Such records can then be used to understand the bidirectional effects of exposures and aging. DISCUSSION/SIGNIFICANCE: Effects of a lifetime of environmental and lifestyle exposures on aging or age-associated diseases are not well understood. Characterizing differential, additive and intense sporadic multi-agent exposures require advanced big data and artificial intelligence methods.

OBJECTIVES/SPECIFIC AIMS: The aim of this study is two-fold (1) to include a participatory action research design in the development of a community-based health advocate (HA) training programme which empowers community members to support the Barbados diabetes remission study 2 protocol – a low-calorie intervention for T2DM remission (2) to study the implementation of this programme with in select faith-based organisations (FBOs) which will act as community hubs. METHODS/STUDY POPULATION: Translation was informed using the RE-AIM framework. The target population were members of select FBOs. We assessed the readiness of FBOs to become community hubs in relation to human resources (the HA team must include someone with a clinical degree), infrastructure capacity (a private room for interviews) and the perspective (knowledge and attitude) of the FBO leadership to both the training and diabetes remission programmes. An open recruitment for HAs was made to the FBO membership and all who responded were accepted to the programme; which consisted of 8 weeks of face to face sessions inclusive of lectures and practical demonstrations and exercises specific to NCDs e.g. assessment of basic clinical parameters, ethics and nutrition. This was followed by a simulation exercise and a formal objective structured clinical examination (OSCE). HAs will participate in focus groups aimed at exploring the barriers and facilitators to the use of social media as a support system; this will be followed by participatory design workshops where the HAs will design support systems, inclusive of social media support, to assist participants in the diabetes remission intervention. RESULTS/ANTICIPATED RESULTS: All three FBOs that were approached responded favourably and the programme was described as ‘necessary’ and ‘timely’ by the leadership. The FBOs were assessed and found to be ready. Thirty-eight persons signed up for the programme (more than the 21 we anticipated); 31 (82%) attended at least 1 session and 29 completed the training; this indicates that implementation in the community is feasible. All who completed the programme attained an overall passing grade indicating the effectiveness of, and fidelity to the training. Initial feedback on the programme from HAs and volunteers indicates that it was acceptable. DISCUSSION/SIGNIFICANCE OF IMPACT: This community-based training programme was successful in terms of reach, as both the FBO and the individual HA responded favourably; and effectiveness as measured by the expanded skill set of the HA. Initial feedback suggests that implementation of the programme is feasible in the community and acceptable to the HAs. Although this model focusses on diabetes remission utilising FBOs as hubs, it can be easily adapted to other NCDs e.g. hypertension and mental health; other disciplines e.g. surveillance; and other communities e.g. workplaces, homeless shelters.

OBJECTIVES/GOALS: Several lines of studies have supported the existence of periodontitis (inflammation of the gums) as a risk factor for cardiovascular disease (CVD). The goal of this study is to evaluate the relationship between periodontitis and CVD among Hispanic, African American, and Caucasian populations. METHODS/STUDY POPULATION: We analyzed data from the National Health and Nutrition Examination Survey, 1999-2004 (NHANES). The population was all adults with a periodontal exam. Periodontal Disease was defined as mild, moderate, and severe (2 loss of attachments of at least 3mm, 2 sites with probing depth of at least 4mm, or one site with probing depth of at least 5mm). Cardiovascular disease was defined by a questionnaire regarding prevalence of any of 5 diagnosis (congestive heart failure [CHF], coronary artery disease [CAD], angina, heart attack or stroke). Data were analyzed using multinomial regression in SAS version 9.3 taking into consideration the design and weight. RESULTS/ANTICIPATED RESULTS: The study included 3375 adults; 13% were Hispanic and 10% were Blacks, 58% had > high school education, 81% were insured, 11% were heavy alcohol drinkers, 27% were smokers, 13% were physically inactive, 14% had periodontitis, 62% visited dentist last year, 2% had CHD, and 1.5% had CHF or stroke. In the multiple multinomial regression, overall, people with periodontitis were more likely to have both CHD (AOR = 2.0, 95% CI = 1.1-3.8, p<0.05) and CHF or stroke (AOR = 1.8, 95% CI = 1.01, 3.0, p<0.05) than to have no heart condition. There was a racial/ethnic difference in the relationship between periodontitis and cardiovascular disease but it was not statistically significant (p>0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: Overall, people with periodontitis were more likely to have CHD, CHF or stroke than to have no heart condition, but with no significant effect of racial/ethnic group. This study provides a foundation to future studies on the connection of periodontitis and CVD in relation to ethnic/racial groups.

OBJECTIVES/GOALS: Previous research has linked inflammation to changes in brain reward circuitry and subsequent negative symptoms in patients with schizophrenia. This project aims to understand brain-immune interactions using diffusion tensor imaging (DTI) to investigate the impact of inflammatory markers on white matter (WM) tracts. METHODS/STUDY POPULATION: Patients with schizophrenia, ages 18 to 45, were recruited at Grady Hospital in Atlanta, GA. All subjects were stable outpatients and underwent extensive medical screening to rule out medical causes of acute inflammation. DTI data was collected from 39 participants on a 3-Tesla Siemens scanner. Blood was collected between 9-11AM for later assay of serum inflammatory markers. Negative symptoms were assessed using the Brief Negative Symptom Scale (BNSS). A diffusion tensor imaging model will be fitted with the data to generate well-known diffusion tensor measures (fractional anisotropy and mean diffusivity). Linear regression will be used to analyze the relationship between DTI measures and inflammation (C-Reactive Protein, CRP), controlling for possible confounders. RESULTS/ANTICIPATED RESULTS: The hypothesis of this proposal is that decreased microstructural integrity in WM tracts between the nucleus accumbens (NAc) and insula will be associated with increased inflammation, which in turn are associated with increased negative symptoms. Negative symptoms include deficits in motivation/pleasure as well as diminished expressivity, and are strongly associated with poor functional outcomes. Based on previous data from this sample demonstrating relationships between CRP and negative symptoms as well as CRP and fMRI functional connectivity between the NAc and insula, we anticipate results that demonstrate similar relationships with WM microstructural integrity, such as functional anisotropy and mean diffusivity. DISCUSSION/SIGNIFICANCE: Given the lack of treatment options for negative symptoms, this research will provide key data to further our understanding of the potential role of inflammation on neural circuits that underlie these symptoms, including WM integrity. This research also has the potential to inform future anti-inflammatory therapies for patients with schizophrenia.

OBJECTIVES/GOALS: Patient reported outcomes (PROs) provide unique insight to the patients experience with their healthcare related quality of life QoL. This study aims to 1. Characterize geriatric trauma patients’(GTPs) perceived QoL, at time of injury vs. 3- and 6-months post-injury. 2. Introduce and validate a PROs tool, known as the Five Favorite Activities. METHODS/STUDY POPULATION: This is a prospective cohort study of older adults (≥65) presenting to our trauma center with mild traumatic brain injury and/or mild spine, thoracic or extremity fractures. Participants will be asked to complete the NIH-validated Patient-Reported Outcome Measure Information System (PROMIS)-29, PROMIS Cognitive and Functional Abilities, Life-Space Levels and Five Favorite Activities assessment (a list of the five favorite overall and daily activities) tools. Cognitive function will be measured using Montreal Cognitive Assessment tool. Physical function will be evaluated using the Activity Measure for Post-Acute Care 6-click tool. Patients will be contacted at 3- and 6- months post discharge and asked to complete the assessment tools listed above to evaluate changes in QoL during the recovery process. RESULTS/ANTICIPATED RESULTS: We hypothesize that geriatric trauma patients will experience a decline in QoL, physical and cognitive function post-injury. This decline will be associated with a decrease in return to the ability to participate in their pre-injury Five Favorite Activities . DISCUSSION/SIGNIFICANCE: First, this study is one of the first to evaluate PROMs in GTPs. Second, the Five Favorite Activities PROM, will provide a unique, direct and individualized characterization of what GTPs find important to their recovery post injury compared to the current generic PROMs. This information can be utilized in the future to align goal of care with expectations

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/Goals: The primary objective of this study is to investigate the relationship between human leukocyte antigen (HLA) alleles to COVID-19 clinical severity, specifically: hospitalization, mortality, pneumonia by COVID-19, post-acute sequelae of SARS-CoV-2 infection (PASC), and clinical lab values. Methods/Study Population: We are conducting a retrospective cohort study utilizing the All of Us controlled tier dataset. The base population was defined as any patients with a COVID-19 diagnosis code (ICD-10: U07.1 or SNOMED: 840539006) and genomic sequencing data. PASC definitions were developed by the N3C consortium and refined in house. A total of 15,252 patients (64.5% female; 50.4% self-reported European ancestry; 18.8% self-reported African ancestry; 34.5% > 65 years old) are included in this study. HLA Class I and Class II alleles will be imputed from a global diversity reference panel utilizing the HIBAG “R” package. Results/Anticipated Results: Controlling for age, sex, race, and COVID-19 vaccination status, we anticipate determining the HLA alleles associated with severe clinical outcomes, such as Pneumonia by COVID (n = 1,436) and PASC (ICD-10:U09.9 or SNOMED:119303003 or OMOP:OMOP5160861 [n = 498]). We will assess which HLA alleles are associated with markedly different IgM and IgG COVID-19 serum antibody levels (n = 1,024). Coexisting conditions, i.e., type 2 diabetes, chronic obstructive pulmonary disease, and hypertension, will be controlled for with the Charlson comorbidity index. The accuracy of HLA allelic imputation will be validated in patients with long-read whole genome sequences. Discussion/Significance of Impact: Our findings can help identify patients who may be at risk of severe COVID-19 infection, particularly those undergoing bone marrow or organ transplantation. We hope this study will accelerate personalized care of COVID-19 in vulnerable populations.

Objectives/Goals: This study aims to explore transcriptional adaptation, where mutations in one gene trigger compensatory changes in related genes, and how this affects the variability in clinical manifestations of ALS. Our findings will provide insights for therapeutic strategies, while we also use gene editing to investigate correcting variants in ALS patients. Methods/Study Population: The presence of a premature termination codon triggers transcriptional activation. Therefore, we utilized CRISPR-Cas9 tool to generate a premature termination codon in CHCHD10 gene in multiple types of cells, including induced pluripotent stem cells derived from patient samples with known CHCHD10 mutations causative for Amyotrophic lateral sclerosis. CRISPR-Cas9 tool was delivered via ribonucleoprotein electroporation and transfected cell’s DNA was sequenced to validate gene editing. To confirm transcriptional adaption, changes in levels of protein and gene expression will be measured via immunoblot and quantification of CHCHD10 and CHCHCD2 from whole cell lysates of the edited cells. Results/Anticipated Results: Utilizing CRISPR-Cas9 tools, we anticipate that CHCHD2 gene can functionally compensate for the loss of function in the CHCHD10 locus through transcriptional adaptation. Additionally, employing single-stranded oligodeoxynucleotides (ssODNs) we aim to accurately correct the genetic aberrations in ALS patient cells, and study the pathomechanisms of aberrant CHCHD10. Discussion/Significance of Impact: The significance of this research lies in its potential to uncover transcriptional adaptation in humans, which could explain why patients with the same genetic variant experience different symptoms. By understanding this mechanism, we could pave the way for novel therapies, especially for CHCHD10-associated ALS.

Objectives/Goals: One in 14 individuals have a substance use disorder (SUD). We suggest that a trait of poor impulse control, or high impulsivity, may predict relapse risk. We explore how changes in brain structure linked to decision-making and reward might drive high impulsivity, helping create a “biosignature” to identify those most at risk and guide treatment choices. Methods/Study Population: Male rats were phenotyped as high impulsive (HI) or low impulsive (LI) based on premature responses on the one-choice serial reaction time (1-CSRT) task. Rats then received an intracranial infusion of a retrograde virus (AAVr2) in the nucleus accumbens (NAc) to trace corticoaccumbens neurons back to the medial prefrontal cortex (mPFC). After impulsivity phenotyping (ITI8), another cohort of animals performed cocaine self-administration followed by 30 days of abstinence. Cue reactivity, a measure of relapse-like behaviors, was performed on abstinence day 30. Analyses of microtubule-associated protein 2 (MAP2), a cytoskeletal marker of dendrites, spines, and somas was performed with western blotting and fluorescent images of brain slices after phenotyping and cocaine abstinence. Results/Anticipated Results: HI rats made greater premature responses, a marker of impulsive action vs. LI rats at baseline (p Discussion/Significance of Impact: Poor inherent impulse control and drug cues heighten relapse risk. We found high impulsivity linked to brain structure differences and lower protein markers of synaptic (units supporting signaling) strengthening. Future investigations into brain-behavior links with impulsivity may further identify a SUD relapse vulnerability biosignature.

OBJECTIVES/GOALS: Our study explores the dose-related effects of THC on cardiovascular measures, self-reported effects, balance, and cognitive function among older adults. We also evaluate the acceptability and feasibility of study procedures, to inform future study designs employing this population. METHODS/STUDY POPULATION: Using a within-subject, double-blind, placebo-controlled design and standard behavioral pharmacology methods, reasonably healthy male and female adults aged 55-70 years undergo an eligibility screening, followed by a mock session and 3 experimental sessions (>7 days apart). During experimental sessions, participants are administered cannabis-infused brownies with varying THC doses. Prior to and at multiple intervals post- consumption, subjects complete assessments including self reports and observer ratings, psychomotor and cognitive performance measures, and vital signs. Follow-up interviews regarding the experience will be conducted one day after each session. RESULTS/ANTICIPATED RESULTS: We anticipate our results to mirror those of previously reported studies conducted in adults under 45 years old in that a dose-response relationship exists for subjective drug effects and vital signs with the caveat that this relationship may be exacerbated in our population. We additionally anticipate findings that indicate THC impairs balance and coordination, potentially increasing the risk of falls and accidents among this population, and cognitive function, affecting attention, memory, and executive functions. Feedback provided during the follow-up interviews will help refine procedures for future studies, ensuring that the methodology is acceptable and feasible for this population. DISCUSSION/SIGNIFICANCE: Prior work demonstrates the safety and efficacy of THC in conditions common among older adults, however, no conclusive data regarding tolerability and safety in this population exists. The presented work is vital groundwork for future research on THC as a potential therapeutic for older adults.

OBJECTIVES/GOALS: Patient beliefs and goals can facilitate discussion of recovery expectations, patient-provider collaboration and maximization of goal achievement. In this study, we sought to address an evidence gap and examine the association of preoperative self-assessment of goals with preoperative and 6-week knee function and gait speed among total knee arthroplasty (TKA) patients. METHODS/STUDY POPULATION: We conducted a secondary analysis of data from the VERITAS randomized, controlled trial conducted from 11/2016-03/2018 that included adults age ≥ 18 years with scheduled and completed unilateral TKA followed by post-surgical physical therapy. Patients rated their ability to perform various activities of daily living goals scaled from 0 (unable to perform) to 10 (full performance). Patients were categorized by pre-surgical (baseline) goal rating: low = 0-2, intermediate = 3-4, and high = 5-10. Outcomes including gait speed and the KOOS were assessed within 10 days prior to surgery and 6-weeks post-surgery. Descriptive statistics and outcomes were compared for patients by preoperative goal rating using Chi-square or Fisher’s exact tests and ANOVA or Kruskal-Wallis tests as appropriate. RESULTS/ANTICIPATED RESULTS: Of 288 patients (mean age 65±8; 62.5% women; 82% white), 102 had a low goal rating (GR), 86 intermediate, and 99 high. Patients with low GR preoperatively generally had lower baseline mean scores than intermediate and high GR patients, respectively, on the KOOS (33.9/35.6/39.8; p<0.001) and lower gait speed (m/s) compared to intermediate and high GR patients at baseline (0.9/1.1/1.0; p = 0.009). The low, intermediate, and high GR groups, respectively, showed no difference across mean KOOS scores (61.0/61.2/61.9; p = 0.63) or gait speed (m/s) (1.0/1.0/1.0, p = 0.33) at 6 weeks postoperative. DISCUSSION/SIGNIFICANCE OF IMPACT: In this study, adults who perceived greater difficulty with a pre-selected activity goal, exhibited lower function prior to TKA but showed no differences in function 6-weeks after surgery. Follow-up studies will describe the association between goal-setting preoperatively and patient goal attainment and satisfaction following surgery.

ABSTRACT IMPACT: The WISE Indiana COVID-19 project facilitates rapid response and access to relevant and emerging evidence-based information for state personnel, healthcare providers and systems, managed care entities, community organizations, and all others involved in a professional capacity with the pandemic response. OBJECTIVES/GOALS: The COVID-19 project was developed to assist in responding to the Indiana Department of Health’s need for rapid and evidence-informed responses to complex questions about the pandemic and best practices for preventing, mitigating, monitoring and recovering from the COVID-19 global pandemic. METHODS/STUDY POPULATION: The WISE Indiana team was activated to assist in managing the project and immediately connected with university research librarians. Through our established networks, we were able to quickly engage academic researchers and clinicians across the state to rapidly respond to key questions about COVID-19 from government leadership. Research librarians added their expertise by conducting comprehensive searches of evidence-based clinical, public health, policy, and law literature and writing up detailed annotated bibliographies. Academic experts were also recruited to write daily summaries of emerging COVID-19 literature for the benefit of Indiana’s frontline responders and build and maintain an online repository of evidence-based learning materials for practitioners on the front lines. RESULTS/ANTICIPATED RESULTS: This work has informed key decision-making at many levels of Indiana’s COVID-19 response. Examples include data modeling for the IN.gov COVID-19 Dashboard, the allocation of Remdesivir, decisions about resuming elective procedures, and strategies for scaling back mitigation efforts. The WISE Indiana team has been able to engage over 40 academic experts from across the state of Indiana with expertise in pulmonary, infectious disease, law, epidemiology, mental health, public health, policy, and communications to assist in responding to key questions posed by government leadership and writing summaries of emerging COVID-19 literature which is summarized and accessible through our website: https://indianactsi.org/community/monon-collaborative/covid-19/. DISCUSSION/SIGNIFICANCE OF FINDINGS: The bidirectional exchange of information through the WISE Indiana collaborative network enable our team to quickly pivot to respond to the needs of our government leadership. Our team was able to rapidly translate the evidence-based information in order to respond to the policy and health outcomes needs of the state’s response to the global pandemic.

ABSTRACT IMPACT: Our research highlights the need for both parental and clinical support to promote PA engagement among higher risk youth with comorbid asthma and obesity; these findings will inform research and clinical efforts in the youth development, prevention science, and clinical psychology fields. OBJECTIVES/GOALS: Asthma incidence doubles in youth with obesity. Physical activity (PA) is beneficial for asthma management; however, parental influence on PA levels among youth with asthma and obesity is poorly understood. This study examines the association of parents and PA among youth with asthma and/or obesity, accounting for risk and protective factors. METHODS/STUDY POPULATION: Data from 5th, 8th, 9th, and 11th-graders were obtained from the 2019 Minnesota Student Survey (N=96,820). Linear regressions examined the impact of parent connectedness on PA across 4 groups (neither asthma nor obesity [OB], asthma only, OB only, comorbid asthma/OB). The p-value for significance was set at p<.001. For PA, youth reported how many days they were physically active (≥60 min/day) in the last week. Two items assessing youth perception of parent care and ability to talk to parents about their problems were used to measure parent connectedness. BMI was calculated using self-report height/weight, age, and gender. Control variables included age, race/ethnicity, and free/reduced lunch eligibility. Models 2-4 retained parent connectedness variables and added risk and protective factors. RESULTS/ANTICIPATED RESULTS: In Model 1, both parent variables significantly predicted PA for each risk group (β ranges: parent care=.07-.09; parent talk=.04-.05, p<.001), except for the asthma/OB group (parent talk: p>.001). Models 2 and 3 added risk factors. Depression was the most salient risk factor, particularly for the highest risk group (asthma/OB; β =-.13, p<.001). Safe neighborhood was positively associated with PA for all groups (βs= .05, p<.001) except the asthma/OB group (p>.001). In Model 4, extracurricular activity involvement (protective factor) was positively associated with PA across all groups (β ranges=: .07-.11, p<.001), and depression remained significant across all groups (β ranges=-.11 to -.14, p<.001). For models 2-4, only parent care remained significant for the neither asthma nor OB group (β =.04, p<.001). DISCUSSION/SIGNIFICANCE OF FINDINGS: Results demonstrate that although parent care is an important protective factor for youth PA engagement, it is less impactful when additional risk factors (e.g., depression) are present, particularly among the highest risk group (comorbid asthma/OB). Thus, clinical support is needed in addition to parent support among higher risk youth.

OBJECTIVES/SPECIFIC AIMS: Given the poor prognosis of HCC and its increasing incidence worldwide, identifying biomarkers of HCC has been an active area of research. While biomarkers are being identified at a rapid pace, many are still in early phases of clinical study and very few have proven clinical utility. The objective of this study is to identify novel biomarkers of HCC and evaluate their clinical utility as predictors of disease development and prognosis with specific emphasis on disease recurrence after liver transplantation. Biomarkers will be identified through GWAS, as well as through analysis of qualitative and quantitative liver traits by magnetic resonance imaging (MRI). These novel biomarkers will then by implemented into risk prediction models aimed to assess an individual’s risk for development of HCC and stratify their level of risk according to predicted disease prognosis. METHODS/STUDY POPULATION: This will be a case-control study, analyzing data from previously created biorepositories from four cohorts of recipients across multiple centers which have undergone liver transplant. First, a GWAS will be performed to identify genetic variant(s). Second, pre-transplant MRI’s will be evaluated using CAVASS software to assess liver quantitative and qualitative traits, including visceral adiposity. Lastly, these findings will be implemented into risk stratification models to assess each individual’s level of risk for development of HCC and for recurrence of HCC after transplant. RESULTS/ANTICIPATED RESULTS: We hypothesize that genetic variant(s) are associated with positive HCV status and the development of HCC. Additionally, we hypothesize that increased visceral adiposity measured by MRI will have an association with recurrence of HCC after transplant. Lastly, we hypothesize that possession of these aforementioned features will be associated with an increased risk of HCC development and recurrence after transplant. DISCUSSION/SIGNIFICANCE OF IMPACT: As more is learned about the nature and reliability of these biomarkers, their potential clinical applications will be revealed. Ideally these proposed risk score models will ultimately be used by clinicians to provide personalized disease management while optimizing the allocation of health care resources. For instance, this may lead to changes in the MRI screening frequency of patients considered to be at high risk for HCC. The ability to diagnose patients early and provide personalized therapies may ultimately result in fewer disease related mortalities in the future.

OBJECTIVES/GOALS: Viral acute rhinosinusitis (ARS), a.k.a, the common cold, affects millions every year. The symptoms caused by viral ARS dramatically affect the general well-being and functional levels of patients, causing work and school absence, and antibiotic abuse. In this study, we examined the therapeutic potential of topical adenosine in viral ARS METHODS/STUDY POPULATION: Rhinosinusitis was induced in WT and adenosine receptor (AR) knockout mice by respiratory syncytial virus (RSV) infection in the upper airways. Mice were subjected to adenosine or vehicle control within the sinuses. Adenosine receptor expression, inflammatory cytokine expression, and histologic mucus and inflammation score was assessed. The effect of endogenous adenosine accumulation within the sino-nasal tract was assessed in adenosine deaminase knockout (ADA-/-) mice. RESULTS/ANTICIPATED RESULTS: Topical administration of adenosine significantly inhibited the expression of pro-inflammatory cytokines, mucus production, and cell damage in the nose of mice with viral ARS, without prolonging virus clearance. This inhibitory effect was primarily mediated by the A2A adenosine receptor (AR). We also examined and compared the expression of ARs in the nasal tissue, trachea, and lungs. The nasal tissue exhibited the lowest baseline expression of ARs as compared to the lung and trachea which was further downregulated following adenosine treatment. Additionally, accumulation of endogenous adenosine in ADA-/- mice showed no signs of inflammation within the nasal tissue. Together, we demonstrated that topical adenosine effectively decreased inflammation and mucus production in a mouse model of viral ARS. DISCUSSION/SIGNIFICANCE: Previously, we found that topical adenosine dramatically enhances mucociliary clearance in the nose and sinuses. In this study, we found that nasal topical adenosine effectively decreased inflammation and mucus production in viral ARS. Our data suggest that nasal topical adenosine is an effective topical therapeutic option for viral ARS.

OBJECTIVES/GOALS: The long-term goal of our lab is to develop clinical and intra-operative methods to aid in assessment of compressive and traumatic peripheral neuropathies. The overall objective of this project is toidentify the potential of serum neurofilament light chain as a diagnostic biomarker for nerve injury. METHODS/STUDY POPULATION: The objective of this prospective study is to obtain data on serum NfL levels in patients with cubital tunnel syndrome and traumatic nerve injuries. Serum NfL from patients with cubital tunnel and traumatic nerve injuries will be compared to serum NfL of asymptomatic, sex and aged matched controls. Pre-operative and post-operative serum levels will be measured and compared topatient’s pre-operative physical exam findings, motor and sensory function testing, electrodiagnostic studies, ultrasound, presence of intraneural vascularity, and post-operative patient reported outcome measures for cubital tunnel patients. For patients with traumatic nerve injury, acute phase and a subsequent serum NfL measurement will be used to assess temporal changes in NfL. RESULTS/ANTICIPATED RESULTS: The central hypothesis of this study is that symptomatic compression of the ulnar nerve or traumatic injury to the brachial plexus leading to axonotmesis will result in measurable increases in serum NfL proportional to the degree of nerve injury. This hypothesis has been formulated based on clinical experience and published studies demonstrating increased expression of serum NfL levels with axonal injury secondary to varying forms of peripheral neuropathy. DISCUSSION/SIGNIFICANCE: The significance of this project is that characterization of the relationship of clinical symptoms, non-invasive imaging and expression of NfL will lead to better diagnostic and prognostic algorithms in the treatment of compressive and traumatic peripheral neuropathies.

OBJECTIVES/GOALS: Diabetes mellitus is a common metabolic disease. Uncontrolled diabetes can lead to complications. The objective of this study is to examine the racial/ethnic variation in the relation between diabetes control and healthy eating, food security, exercise, and access to health care. METHODS/STUDY POPULATION: We analyzed data related to diabetes control, demographics, insurance, healthy eating, food security and physical activity for 949 diabetics from the National Health and Nutrition Examination Survey (NHANES). The population examined was adults with diabetes mellitus. Diabetes control was classified as fair control [HbA1c 7-<8 and fasting glucose <126 mg/dL], good control [HbA1c<7 and fasting glucose <110 mg/dL] or uncontrolled [HbA1c8 and fasting glucose <110 mg/dL]. We used multinomial logistic regression controlling for confounders to analyze the data overall and for each racial/ethnic group and report adjusted odds ratios (AOR) and 95% confidence limits (CL). RESULTS/ANTICIPATED RESULTS: Of the 949 diabetics, 14.7% were Blacks, 15.9% were Hispanics, 11.0% had fair control, 61.0% had good control, 14.2% were uninsured, 18.1% had low/very low food security, and 39.7% were inactive. Overall, uninsured subjects had a lower chance of fair diabetes control (AOR = 0.2, 95% CL = 0.1-0.9, p = 0.04), but this relationship was significant only for Hispanics and Blacks (p<0.05). Whites with low/very low food security were less likely to have fair control (AOR = 0.2, 95% CI = 0.001-0.9, p = 0.04). Blacks who were inactive, and insufficiently active Hispanics had a lower chance of good/excellent diabetes control (AOR = 0.5, 95% CI = 0.2-0.9, p = 0.03; AOR = 0.3, 95% CI = 0.1-0.7, p = 0.007 respectively). DISCUSSION/SIGNIFICANCE OF IMPACT: The results show the importance of insurance coverage, food security and physical activity in diabetes control among different racial/ethnic groups. They indicate a need for affordable health care and for culturally-relevant interventions that include physical activity and food security.

In addition to facing numerous healthcare disparities, rural America is chronically underrepresented in clinical research. This gap was made more evident during the COVID-19 pandemic. St Lawrence Health, located in rural Upstate New York, established its Clinical and Rural Health Research Department in 2015 to help close this gap. The research department then launched the DISRUPTS (Developing InfraStructure for Research to Utilize Patient-centered Techniques at St Lawrence Health System) program to build the infrastructure to conduct Patient-Centered Outcomes Research (PCOR). Together with a diverse committee, the team used proven methods and frameworks to develop a model for engagement, content creation, and education delivery that was successfully used to create educational programs on PCOR and COVID-19. The resulting DISRUPTS webinars had a combined total of over 450 live attendees and over 1,110 views on recordings. Furthermore, nearly one-third of those who participated in the COVID-19 vaccines webinar indicated they were more likely to receive a COVID-19 vaccine after taking part. DISRUPTS can serve as an important model for other rural communities that aim to increase access to and engagement in PCOR, and which hope to improve outreach and education efforts in their communities.