OBJECTIVES/GOALS: Weaimed to compare subjective and objective sleep in individuals with chronic post-concussive symptoms. We hypothesized an association between self-reported sleep quality and objective sleep parameters, which is different for concussed and control cohorts. METHODS/STUDY POPULATION: 28 individuals with chronic post-concussive symptoms and 13 age-matched controls (no concussion history) completed the ISI, PSQI, PROMIS Depression, Anxiety, Stress and Cognitive questionnaires at enrollment. Objective sleep parameters were obtained for a minimum of 7 days and up to 30 days with a validated sleep monitoring device placed under the subject’s bed (Emfit). For each night, raw activity data per minute were analyzed to determinein-bed, sleep, wake, andout-of-bedtimes. These measures were used to calculate total sleep time (TST), sleep onset latency (SOL), and wake after sleep onset (WASO) for each night. RESULTS/ANTICIPATED RESULTS: Concussed individuals reported worse sleep with PSQI and ISI scores significantly higher than controls. They also showedsignificant associations between PSQI and Dep ression, ISI and Depression, and ISI and Anxiety scores. There was no difference between objective sleep parameters in the concussed and control cohorts (in-bed/sleep/wake/out-of-bed times, TST, SOL, and WASO). Instead, higher PSQI, ISI, Depression, Anxiety, and Stress scores (greater symptom burden) were all associated with later sleep times, where as higher Cognitive scores (greater cognitive function) were associated with earlier sleep times, regardless of group status. DISCUSSION/SIGNIFICANCE: Concussed individuals report worse subjective sleep but no differences to controls when objectively assessing sleep. Depression/anxiety, and not concussion status, determine objective sleep parameters. Psychiatric comorbidities should inform the treatment of post-concussive sleep disturbances.

OBJECTIVES/GOALS: Effective translation of data to inform real-time patient care is lacking in addiction inpatient settings. The current study presents the optimization of a Comprehensive Rehabilitation Assessment summary report that is used by clinicians to individualize treatment. METHODS/STUDY POPULATION: A multi-aim approach was taken that utilized aspects of various implementation science frameworks. Participants were clinical staff (N = 7; female = 71%). A quantitative survey was used for aims 1 and 2 to assess motives and context around the report as well as evaluate the design of it. Aim 3 focused on optimization via semi-structured interviews. Descriptive and modified content analyses were utilized appropriately for each aim. RESULTS/ANTICIPATED RESULTS: Five versions of the assessment report were created between February 2021 and August 2022, the most recent of was adapted into patients’electronic medical records based on study results. Each report version, participants’results/feedback, and researchers’perceived barriers to this translational process will be discussed. DISCUSSION/SIGNIFICANCE: The current study highlights a replicable approach for optimizing the translation of assessment data into treatment for patients with disorders of addiction.

OBJECTIVES/SPECIFIC AIMS: The primary objective of this study was to evaluate the performance of a bone fracture targeted systemically administrable bone anabolic as a potential therapeutic for bone fracture repair. Currently all bone fracture repair therapeutic require local administration during surgery. However, the population that need the most assistance in repair bone fractures are not eligible for surgery. So, it was our goal to design an inject-able therapeutic to assist in bone fracture repair to reduce the invasiveness. The injectable nature of it allows for repair administration of the bone anabolic and for therapeutic effect throughout the entire bone fracture healing process. Targeting it to the bone fracture site reduces the toxicity and increases the efficacy. METHODS/STUDY POPULATION: METHODS To achieve the above objective, a bone mineral-(hydroxyapatite-) targeting oligopeptide was conjugated to the non-signaling end of an engineered parathyroid hormone related protein fragment 1-46 with substitutions at Glu22,25, Leu23,28,31, Aib29, Lys26,30 (ePTHrP). The negatively charged oligopeptide has been shown to target raw hydroxyapatite with remarkable specificity, while the attached PTHrP has been demonstrated to induce sustained and accelerated bone growth under control of endogenous morphogenic regulatory factors. The conjugate’s specificity arises from the fact that raw hydroxyapatite is only exposed whenever a bone is fractured, surgically cut, grafted, or induced to undergo accelerated remodeling. The hydroxyapatite-targeted conjugate can therefore be administered systemically (i.e. without invasive surgery or localized injection) and still accumulate on the exposed hydroxyapatite at the fracture site where it accelerates the healing process Murine in vivo experiments were conducted on female Swiss Webster mice (10 per group). Femoral fractures were induced with a 3-point bending device and stabilized. Mice were dosed with 3 nmol/kg/d of targeted-ePTHrP, non-conjugated (free) ePTHrP, or saline. Following a 4-week study, fracture callus densities were measured using microCT. Canine in vivo experiments were conducted on 1-year-old male beagles. Beagles underwent a 10 mm bilateral ulnar ostectomy. Two dogs in the treatment group and Three dogs in the control group were dosed daily with either targeted-ePTHrP 0.5nmol/kg/d or saline respectively. Dogs were x-rayed weekly for the first 6 weeks and then every other week thereafter. One tailed ANOVA followed by Dunnett’s post-hoc test was used to establish significance. All animal experiments were conducted as described in approved IACUC protocols. P<0.05 was considered significant. RESULTS/ANTICIPATED RESULTS: RESULTS SECTION: In the murine studies we observed a marked increase in fracture callus size and a 2-fold increase in bone deposition was observed in the targeted-ePTHrP group over the saline group (P<0.01). A significant doubling in bone density was also observed. Targeted-ePTHrP group fractured femurs were able to achieve their pre-fracture strength as early as 3 weeks compared to 9 weeks in the saline mice representing a 66% reduction in healing time. In the canine studies, we observe a significantly higher closure of the ostectomy gap than saline controls (P<0.05). In addition, no significant differences in weight are observed in the treatment vs. saline controls. No significant difference between the control group and treatment groups was found in a histological investigation of the organs. DISCUSSION/SIGNIFICANCE OF IMPACT: DISCUSSION: Although attempts have been made in developing a systemically administered fracture therapeutic for fracture repair, i.e. teriparatide, to date, no such anabolics have been approved for this use. In these studies there is evidence that anabolic activity was occurring at the fracture site, but at a level that did not meet FDA required end-points.2 It is plausible that if sufficient drug were to be delivered to a fracture site then improved fracture repair would be possible. In previous studies, we demonstrated fracture specific accumulation bone anabolics can be achieved by modifying the drug with acidic oligopeptides.3 Here, by modifying a safe, clinically proven, parathyroid hormone receptor agonist with an acidic oligopeptide we observe improved bone deposition and strength in mice. Furthermore, when administered to canine critical sized defect ostectomies, a more relevant and difficult model, we observe improved ostectomy closure. CLINICAL RELEVANCE:: The ability to accelerate bone fracture repair is a fundamental need that has not been addressed by conventional methods. By targeting bone anabolic agents to bone fractures, we can deliver sufficient concentrations of anabolic agent to the fracture site to accelerate healing, thus avoiding surgery and any ectopic bone growth associated with locally-applied bone anabolic agents.

OBJECTIVES/GOALS: Despite the importance of addressing maternal weight to promote healthy pregnancies, previous gestational weight management programs have overlooked rural women. Accordingly, this study used an optimization framework to develop and refine a prototype for an online gestational weight management intervention targeting rural women. METHODS/STUDY POPULATION: Methods were guided by the Obesity-Related Behavioral Intervention Trials (ORBIT) model, an optimization framework focused on intervention development and refinement. In line with this framework, three major steps were followed. First, qualitative interviews were conducted with 16 rural women who were currently or had recently been pregnant to identify barriers, facilitators, and desired resources for gestational weight management. A template analysis approach was applied to the resulting interview transcripts to identify pertinent themes. Second, themes derived from the initial interviews were used to inform the development of an online intervention prototype. Third, feedback on this prototype was sought from an additional sample of 15 rural women who were currently or had recently been pregnant. RESULTS/ANTICIPATED RESULTS: Themes from the initial interviews highlighted numerous barriers, facilitators, and desired resources for rural gestational weight management that aligned with common social determinants of health (e.g., neighborhood and built environment, social and community context) and pregnancy-specific factors. Women also described wanting an online gestational weight management program that included a user-friendly interface, psychoeducation, tailored health recommendations, accountability, and simple behavior-logging tools. Using this feedback, an online intervention prototype was developed. Results from the feedback interviews are currently being qualitatively analyzed for themes and will be used to further refine the prototype prior to feasibility testing. DISCUSSION/SIGNIFICANCE: This study used an optimization framework to develop an online intervention aimed at supporting healthy maternal weight outcomes in rural communities. Because rural women experience notable weight disparities compared to their urban peers, this intervention has the potential to promote more equitable maternal health outcomes in rural areas.

OBJECTIVES/GOALS: This project aimed to examine the impacts of biological sex and alexithymia on frontal lobe connectivity in executive functioning (EF)-related neural networks during successful inhibition as a means to index vulnerability for future cognitive decline. METHODS/STUDY POPULATION: Healthy, cognitively intact older adults (n=43, 33 female, Mage=79) completed the 20-item Toronto Alexithymia Scale (TAS-20) and the stop-signal task in this study. We used electroencephalography (EEG) source estimation to investigate EF-related frontal connectivity during successful inhibition in stop-signal task trials. Connectivity was measured in bilateral frontal ROIs relevant to inhibition using time series correlations over the N200 (186-350ms) and P300 (340-616ms) time windows, associated with the inhibitory subprocesses of conflict processing and performance evaluation, respectively. RESULTS/ANTICIPATED RESULTS: Those with higher alexithymia, as measured by the difficulty identifying feelings (DIF) facet of the TAS-20, had lower right anterior cingulate cortex (ACC)-left superior frontal gyrus (SFG) connectivity in the P300 window, suggesting impaired performance evaluation. Further, in females specifically, those with higher DIF had greater right inferior frontal gyrus (rIFG)-bilateral ACC connectivity in the N200 window than those with lower DIF, suggesting greater resources were allocated for conflict processing and inhibition. Right ACC-rIFG connectivity also correlated with better stop accuracy and faster stop-signal reaction time, supporting this network’s role in successful inhibition. DISCUSSION/SIGNIFICANCE: Overall, during successful inhibition, higher DIF was associated with reduced performance monitoring efficiency as well as greater resource allocation for conflict processing during motor stopping in women only. Thus, alexithymia (via DIF) may exacerbate age-related EF dysfunction and risk for future cognitive decline, especially for females.

OBJECTIVES/GOALS: Virtual surgical planning and 3D printing enable streamlined surgeries and increased complexity. These technologies, however, require CT scans and radiation exposure. This project’s goal is to optimize and demonstrate the accuracy of Black Bone MRI for surgical planning in reconstructive surgery. METHODS/STUDY POPULATION: Four common craniofacial surgeries were planned and performed on cadaver specimens (maxillary advancement, orbital floor reconstruction with patient-specific implants, cranial vault reconstruction, and fibular free flap reconstruction of the mandible). For each surgical procedure, ten cadaver heads were used. Five of each surgery were planned and 3D printed guides were created utilizing Black Bone MRI versus five with CT scans. Following mock surgeries, all specimens underwent a post-operative CT scan. 3d reconstruction was performed and surgical accuracy compared to the plan was assessed using GeoMagic Wrap, assessing average post-operative deviation from plan. RESULTS/ANTICIPATED RESULTS: In all surgeries, guides created from Black Bone MRI demonstrated high accuracy to surgical plan. Average osteotomy (cut) deviation from plan was not statistically significantly different when Black Bone MRI was used compared to CT scans for planning and guide creation in the wide variety of craniofacial surgeries performed. The average deviation of post-operative anatomy from pre-operative plan was also not statistically significant when Black Bone MRI versus CT scans were utilized in the surgeries. These results then enabled the translational application of this technology clinically, and we demonstrate a clinical reconstructive craniofacial case planned utilizing Black Bone MRI. DISCUSSION/SIGNIFICANCE OF IMPACT: This study demonstrates that virtual surgical planning and 3d surgical guide creation can be performed using Black Bone MRI with comparable accuracy to CT scans in a wide variety of craniofacial procedures. This could dramatically reduce radiation exposure for patients. The successful segmentation, virtual planning, and 3d printing of accurate guides from Black Bone MRI demonstrate potential to change the pre-operative planning standard of care. This project, overall, also demonstrates the development of new solutions to advance clinical care, thus serving as an example of moving translational science from a concept to the operating room.

ABSTRACT IMPACT: As newborn screening is now available for X-linked adrenoleukodystrophy, there is a need to establish meaningful disease markers to detect the onset of the severe demyelinating cerebral form of this disease at the earliest possible stage, and to quantify early disease progression to evaluate the relative efficacy of therapies. OBJECTIVES/GOALS: Longitudinal testing of neurocognitive and motor function using smartphone and tablet-based applications holds promise for early detection and quantification of brain white matter changes in patients with adrenoleukodystrophy (ALD) and other rare demyelinating diseases, but this methodology requires validation in pediatric populations. METHODS/STUDY POPULATION: We developed an iPad application with a game-like interface to assess interhemispheric transfer across the corpus callosum, the brain structure where cerebral demyelinating disease typically begins in patients with ALD. Feasibility data from remote test administrations with healthy children were collected to analyze and speed and timing of finger tapping movements requiring bimanual coordination on a touchscreen. RESULTS/ANTICIPATED RESULTS: Among our pilot sample of healthy school-aged children, age-related improvements in finger tapping speed were observed in both single-hand and alternating-hand conditions. Results indicate that remote testing using iPad applications is a viable way to collect psychometric testing data rapidly in pediatric populations and is feasible during a pandemic. Next steps in this research project will be: (1) evaluating the stability of repeated test administrations (test-retest reliability), (2) assessing agreement between performance on our iPad application and validated measures of interhemispheric transfer and fine motor function, and (3) comparing performance of children with known corpus callosum white matter abnormality to performance of healthy children. DISCUSSION/SIGNIFICANCE OF FINDINGS: Brief neurocognitive tests that can be frequently administered may have the ability to capture subtle brain changes in developing children. Approaches enabling remote (virtual) testing will facilitate research during the covid-19 pandemic and are especially well-suited for data collection in rare disease populations.

In this paper, we address how the COVID-19 pandemic has impacted informed consent for clinical research through examining experiences within Clinical and Translation Science Award (CTSA) institutions. We begin with a brief overview of informed consent and the challenges that existed prior to COVID-19. Then, we discuss how informed consent processes were modified or changed to address the pandemic, consider what lessons were learned, and present research and policy steps to prepare for future research and public health crises. The experiences and challenges for CTSA institutions offer an important perspective for examining what we have learned about informed consent and determining the next steps for improving the consent process.

OBJECTIVES/GOALS: To compare the opioid drug requirements amongst those individuals with high levels of catecholamines in blood and acute post-procedural pain, by ICD9/10 codes (experimental) to those with normal levels of catecholamines and acute post-procedural pain (AP-PP) only (controls) METHODS/STUDY POPULATION: In collaboration with both the Informatics and the Biostatistics Departments at CTSI and under the auspices of the IRB at the University of Rochester, we completed the collection of ~8,000 electronic health records(EHRs) of adults 18 years and older with surgical appointments at Strong Memorial Hospital (SMH), who met inclusion criteria, from January 2006 to September 2019 and received Fentanyl therapy for AP-PP management. Subjects were categorized in a two-arm-matched case-control fashion. A ratio of 1(Experimental):1(Control) was utilized. Analytic comparisons were completed using normal distribution statistical methods with p >0.1 for significance. RESULTS/ANTICIPATED RESULTS: After removal of duplicates and exclusion of EHRs, a total of 17 subjects met inclusion criteria for the experimental group. We matched controls (n = 17) with experimental subjects for age, gender and surgical procedure for accurately compare opioid requirements in the postoperative recovery. Mean age of subjects was 69(+/-10.1235) years old. Most of subjects were females (70%). Mean Fentanyl requirement was significantly different in the experimental group 466.17(625.621)mcg compared to 215.58(353.323)mcg in the controls (p value 0.07832) DISCUSSION/SIGNIFICANCE OF IMPACT: It is suggested that healthy individuals with genetic variations in pain pathways including; the COMT and MAOA rendered individuals with higher levels of catecholamines in the body driving abnormal responses to pain sensitivity. We emulated this genetic variation for clinical purposes using ICD10/9 codes of those with conditions related to higher catecholamine levels in the body. Based on our preliminary results, we suggest that COMT and MAOA genetic variations could impact opioid drug use and the current opioid dependency and epidemics in the U.S. This study will address remarkable questions and identify strategies about this topic.

OBJECTIVES/GOALS: 1) Investigate the utility of pragmatic communication profiles in a sample of children with autism at baseline to predict response to treatment in a randomized clinical trial (RCT) of oxytocin augmentation and social cognitive skills training at week 12. 2) Determine if levels of anxiety or hyperactivity moderate child outcome performance. METHODS/STUDY POPULATION: 40 children (37M, 3F), aged 8-11(M=9.25, SD=1.10), with confirmed autism spectrum disorder (ASD), enrolled in an RCT(NCT02918864) were evaluated at baseline on: an assessment of ASD (Autism Diagnosis Observation Schedule, ADOS-2), a task of perspective taking, Theory of Mind ToM, (Reading the Mind from the Eyes Task), pragmatic communication (Pragmatic Rating Scale-School Aged; PRS-SA), IQ (WAIS_I, WISC-V) and anxiety and hyperactivity (Behavior Assessment Scales for Children-3; BASC-3). A Tobii T60 XL was used for eye-tracking visual patterns and attention during the RMET. The PRS-SA was coded by trained, reliable clinicians. Parent ratings indicated over half of the participants’ had At Risk levels or higher on anxiety and hyperactivity on the BASC-3. Week 12 measures included all but the PRS-SA and ADOS-2. RESULTS/ANTICIPATED RESULTS: Baseline preliminary analysis indicated the participants spent more time looking at words (.41ms) than eye images on the RMET(.15ms, p DISCUSSION/SIGNIFICANCE: Findings at baseline suggest pragmatic communication skills are more related to ToM than gaze and attention on the RMET. This relationship will be further investigated over the time of the trial. Mental health indicators need to be considered further in this population. Child profiles at baseline may inform appropriate triage and treatment targets.

OBJECTIVES/GOALS: Globally, diabetes affects 537 million people and 15-25% will develop a foot ulcer in their lifetime. Diabetic foot ulcers (DFU) tend to be chronic and non-healing due to the poor wound healing environment, leading to infection or amputation. Our study aims to develop a method to predict and prevent DFU formation. METHODS/STUDY POPULATION: Our preliminary plan is to develop a method to detect high plantar pressures, coupled with the ability to automatically adjust an orthotic device to offload excess pressure. Our current aim is to create a “smart orthotic” which will link with foot mapping technology to automatically offload high pressure areas, reducing the need for a separate clinic visit for orthotic adjustment. We aim to prove that our device will normalize plantar pressure distribution, which will prevent callus and subsequent DFU formation. The current target population includes those with diagnosed diabetes and are ambulatory. RESULTS/ANTICIPATED RESULTS: With our technology, we anticipate normalization of plantar pressure distribution in a more frequent fashion than is currently done. Because annual orthotic fittings, which is current standard of care, do not provide regular enough adjustments to match the rate of diabetic foot structural changes and peak plantar pressure redistribution, our device will address two gaps in management. One, patients will receive near-instantaneous changes in plantar pressure offloading, allowing for near continuous orthotic customization. Secondly, our device would reduce the clinical appointment burden, which would be especially important for patients with multiple medical comorbidities or experience other barriers to accessing healthcare. DISCUSSION/SIGNIFICANCE: While DFUs are commonplace and their complications are well recognized, there still exists a gap in ulcer prevention. Our proposed solution will redistribute pathologic plantar pressures, allow for more frequent monitoring, automatic therapy, and aid in the management of high ulcer risk patients.

OBJECTIVES/SPECIFIC AIMS: The current study is the first investigation of frontal alpha asymmetry in distressed violent (DV) and distressed nonviolent (DNV) partners during a placebo-controlled alcohol administration and emotion-regulation study. Because this is the first study of the pharmacological effects of alcohol on FAA, the first portion of the study was conducted to characterize alcohol effects in DV and DNV partners during the baseline condition. The subsequent portions of the study were conducted to characterize the effects of alcohol and evocative stimuli on FAA in DV and DNV partners. We hypothesized that DV partners would demonstrated greater left frontal alpha asymmetry when intoxicated and viewing evocative partner stimuli than DNV partners. Lastly, we attempted to replicate previous research that has found associations between baseline measures of FAA and the State-Trait Anger Expression Inventory – 2 (Spielberger, 1999) subscales of Trait Anger, Anger Expression-Out, Anger Expression-In, Anger Control-Out, Anger Control-In (Hewig, Hagemann, Seifert, Naumann, & Bartussek, 2004). METHODS/STUDY POPULATION: Partners in the present study were drawn from a larger study investigating over-arousal as a mechanism between alcohol use and intimate partner violence (AA022367). Couples were recruited from the community via radio, television and newspaper advertisements, and eligibility screening occurred at the couple level. Participants included in the present analysis were 23 DV partners (12 female, 11 male), and 15 DNV partners (7 female, 9 male). The mean age of the sample was 32 (SD 4.8 years, range 23-40 years). Data from two DV partners were not included in the analyses of the FAA in the emotion-regulation tasks due to movement artifacts during the alcohol condition leaving too little data for analysis. RESULTS/ANTICIPATED RESULTS: The expected beverage by couple type interaction did not reach significance [F (1, 36) = 3.93, p = .055], but the between-subjects effects of couple type revealed a significant difference [F (1, 36) = 4.425, p = .042]. Contrary to our hypothesis, however, these results suggest that under conditions of alcohol, DV partners evidenced significantly greater relative right frontal alpha power asymmetry whereas DNV partners evidenced greater relative left frontal alpha power asymmetry. Although there was no significant between-subjects effect, there was a nearly significant interaction between beverage type and emotion regulation condition [F = (1, 36) = 4.032, p = .052] and a significant main effect of emotion regulation condition [F (1, 36) = 7.579, p = .009]. It appears that asking the participants to “not react” to their partners’ evocative stimuli caused significantly greater right frontal alpha asymmetry. Because intimate partner violence is best understood in the context of conflict between two partners, we also examined partner-reported experiences of anger as predictors of DV participant’s FAA. The model as a whole predicted 67.4% of the variance in DV partner FAA, R squared change =.674, F Change (5, 15) = 6.21, p = .003. Three anger experience scales were statistically significant. The partner Anger Control-Out (B = -1.23, p =.001) scale recorded a higher standardized beta value and accounted for 40% of the variance in this model. Anger Control-In (B = .63, p = .022) accounted for 14% of the variance in the model, and Anger Expression-Out scale (B = .57, p = .024) accounted for 13.7% of the variance in the model. DISCUSSION/SIGNIFICANCE OF IMPACT: The current study is the first pharmacological study of the effects of alcohol on frontal alpha asymmetry in distressed violent and distressed nonviolent partners. Contrary to our hypothesis, under acute alcohol intoxication during the baseline condition, DV partners exhibited significantly greater relative right FAA compared to DNV partners who exhibited significantly greater relative left FAA. Because intimate partner violence is best understood in the context of couple conflict, we examined the ability of partners’ anger experiences to predict DV and DNV partners’ FAA, and a very interesting pattern emerged among our DV participants and their partners. The anger experiences of our DV participants’ partners accounted for 67% of the variance in the FAA of our DV participants when they were intoxicated and viewing evocative stimuli.

ABSTRACT IMPACT: Through its interdisciplinary, tailored approach, the FLOW program could change the way that we approach promoting healthy lifestyle changes in the primary care field. OBJECTIVES/GOALS: The goal of this project is to assess patient outcomes associated with the implementation of the Fitness, Lifestyle, and Optimal Wellness (FLOW) Program. The ultimate aim of this program is two-fold: increasing patient-reported wellness and improving objective health measurements. METHODS/STUDY POPULATION: The FLOW program consists of a multidisciplinary team of sports medicine physicians, nutritionists, fitness trainers, and clinical psychologists. Patients who choose to participate in the program undergo a comprehensive physician-guided assessment, including lifestyle and metabolic evaluation, biomarker profile, and body composition analysis. Based on the patient’s goals and results of evaluation, he/she is then connected with other members of the FLOW team to develop a comprehensive plan and offer resources for potential improvements in physical activity, nutrition, and/or behavior. The patient will undergo follow-up assessments and questionnaires at three and six months to track their objective measurements and reported progress. RESULTS/ANTICIPATED RESULTS: The anticipated results of the FLOW program are an overall improvement in patient health and wellbeing. More specifically, we anticipate seeing increased levels of exercise from initial reported levels, as well as better nutrition habits. We expect to see improvements in follow-up body composition assessments, with gains in fat-free mass and decreased body fat, in addition to patient-reported improvements in behavioral health as measured by PHQ-9, GAD-2, and the Perceived Stress Scale. We will also assess reported sleep health with the hopes to see improvement in follow-up assessments. DISCUSSION/SIGNIFICANCE OF FINDINGS: The FLOW program is designed to address health inequities that disproportionately affect the Deep South. Through this program, we propose a new role of the primary care team in promoting healthy lifestyle habits and disease prevention through exercise, nutrition, and behavioral health services.

Regulatory Science

OBJECTIVES/GOALS: The Monte Carlo dose calculation method is often considered the “gold standard” for patient dose calculations and can be as radiation dose measurements. Our study aims to develop a true Monte Carlo model that can be implemented in our clinic as part of our routine patient-specific quality assurance. METHODS/STUDY POPULATION: We have configured and validated a model of one of our linear accelerators used for radiation therapy treatments using the EGSnrc Monte Carlo simulation software. Measured dosimetric data was obtained from the linear accelerator and was used as the standard to compare the doses calculated with our model in EGSnrc. We will compare dose calculations between commercial treatment planning systems, the EGSnrc Monte Carlo model, and patient-specific measurements. We will implement the Monte Carlo model in our clinic for routine second-checks of patient plans, and to recalculate plans delivered to patients using machine log files. RESULTS/ANTICIPATED RESULTS: Our Monte Carlo model is within 1% agreement with our measured dosimetric data, and is an accurate representation of our linear accelerators used for patient treatments. With this high level of accuracy, we have begun simulating more complex patient treatment geometries, and expect the level of accuracy to be within 1% of measured data. We believe the Monte Carlo calculation based on machine log files will correlate with patient-specific QA analysis and results. The Monte Carlo model will be a useful tool in improving our patient-specific quality assurance protocol and can be utilized in further research. DISCUSSION/SIGNIFICANCE OF IMPACT: This work can be implemented directly in clinical practice to ensure patient doses are calculated as accurately as possible. These methods can be used by clinics who do not have access to more advanced dose calculation software, ensuring accuracy for all patients undergoing radiotherapy treatments.

OBJECTIVES/GOALS: Compare metabolic health of type 2 diabetics on GLP-1 to those on traditional therapy METHODS/STUDY POPULATION: Outcomes of interest of this study include analyzing GLP-1 agonists on overall metabolic health, focusing primarily on weight loss and ability to wane off insulin without rebounding metabolic health. The data will be collected in a retrospective chart review from medical records of type II diabetics from Children’s of Alabama and will follow patients over two years. The charts have been narrowed to those patients prescribed GLP-1 agonists who have been on the medication for at least one year with consistent visits to the endocrinology clinic.The following data will be collected from the charts:race/ethnicity, date of visit, BMI/weight, A1C, insulin therapy, lipids, LFTs (AST/ALT), and insurance coverage RESULTS/ANTICIPATED RESULTS: With these results, we hope to study the metabolic health effects of GLP-1 agonists on type II diabetes in the pediatric population. It is known that obesity is a risk factor for type II diabetes, and that GLP-1 agonists aid in weight-loss in adults. Further research is needed to see the real world health effects, and with these results we hope to assess if GLP-1 agonist have an affect on metabolic health within the pediatric population by collecting data on values aforementioned. We also hope to compare and contrast the different GLP-1 agonists being used based on adherence, insurance coverage, adverse effects, and patient preference. Currently, only Liraglutide and Exetanide are approved for pediatric type II diabetics. DISCUSSION/SIGNIFICANCE: Insulin use can lead to weight gain; metformin does not aidin weight reductions. If GLP-1 agonists aid in weight loss, it could potentially help slow complications of diabetes in the pediatric population. B-cell function in children declines more rapidly; and, as a result, insulin resistance occurs more rapidly.

ABSTRACT IMPACT: Alterations in mitochondrial metabolism affect any tissue, especially those with the highest demand for energy. As the symptoms and clinical manifestations are heterogenous, disease diagnosis is challenging. The implementation of genetic-first approach in the diagnosis of mitochondrial diseases will expedite confirmation, treatment, management, and counseling of affected Puerto Rican individuals. OBJECTIVES/GOALS: Mitochondrial diseases are rare, and diagnosis is complex due to the heterogeneity of clinical manifestations. We aim to develop and implement a testing algorithm using a genetics-first approach, facilitating the identification of variants that contribute to mitochondrial disease’s etiology and influence onset and progression in Puerto Ricans. METHODS/STUDY POPULATION: This is a cross-sectional study for characterizing clinical laboratory results from profiles used to evaluate metabolic diseases in individuals with suspected mitochondrial disorders from 2018 to 2021. A subset of 25 individuals from biochemical profile will be recruited to analyze their medical and family history, metabolic biomarkers in blood and urine, hearing test, imaging and chromosomal microarray. The implementation of a genetic testing algorithm using whole exome and mitochondrial DNA sequencing will be performed in a subset of 11 randomized individuals. Descriptive analysis will be reported, including a catalog of all variants. Multivariate analysis will be performed to estimate the statistical association between variants and phenotypes reported and adjusting for potential confounders. RESULTS/ANTICIPATED RESULTS: The biochemical profile of pediatric Puerto Rican individuals suspected of having mitochondrial diseases will be altered and can be used to differentiate among other metabolic causes. We expect to find altered levels of lactate, pyruvate and carnitines in serum, as well as altered organic acids in urine. The implementation of a testing algorithm using both, mitochondrial DNA and whole exome sequencing as first approach will be enabling the identification of disease-causing variants, thus enhancing and confirming the diagnosis of mitochondrial disease in Puerto Ricans. We will be able to identify rare/novel variants specific to our Hispanic population, for both nuclear and mitochondrial DNA. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study will help to characterize the metabolic profile of pediatric Puerto Ricans. No previous study has been reported that describes testing algorithms for genetic diagnosis of mitochondrial disease in our population. Variants found will contribute to a deep understanding of the genetic contribution to phenotypes and disease susceptibility.