OBJECTIVES/GOALS: Despite the large body of evidence concerning the effects of dietary interventions on blood pressure, trials have often reported poor adherence to sodium restriction. We implemented the Sodium Watcher Program-Hypertension (SWPH) program using digital self-monitoring. The purpose of this study was to determine the feasibility of the SWPH program. METHODS/STUDY POPULATION: The SWPH is a pilot two-arm, 2-month randomized controlled trial that enrolls adults with hypertension. The intervention group received personalized feedback on dietary sodium intake and BP and the control group participants received usual care for hypertension. Both groups participated in digital self-monitoring of daily diet and BP over 8 weeks. The primary outcomes were adherence to dietary sodium intake as captured by 24-hour urinary sodium excretion and BP at baseline and at the 2-month follow-up. Feasibility assessment included adherence to dietary sodium intake monitoring and in-home BP monitoring measured by the percentage of days that participant logged their food intake and in-home BP. The preliminary effect on the outcome variables was tested by using a repeated-measures analysis of variance. RESULTS/ANTICIPATED RESULTS: In this feasibility study, we included data from 12 participants (n=9 SWPH, n=3 control) who completed all phases of the study. The patients median age was 56.5 years and 70% were female. The mean baseline BP was 142.7/87.5 mmHg. The mean 24-hour urine sodium of 4853.0 mg (SD=1639.9 mg) with 80% having 24-hour urine sodium >2300 mg at baseline. SWPH group had lower systolic (baseline 142.4 mmHg vs follow-up 124.1 mmHg, p<0.001), diastolic (baseline 87.1 mmHg vs follow-up 77.5 mmHg, p<0.05) BP, and 24-hour urine sodium (baseline 3790.4 mg vs 2609.7 mg, p<0.05) compared with control group. Compared with the control group, the SWPH group had significantly more eligible days of digital food log usage (control 80.0% vs intervention 98.2%, p<0.01) and in-home BP monitor usage (control 77.6% vs intervention 94.6%, p<0.01). DISCUSSION/SIGNIFICANCE: Millions of Americans remain in need of effective interventions to manage their hypertension. Innovative and accessible strategies to sustain a low sodium diet intervention are needed for the majority of individuals not following the low sodium diet. By leveraging digital self-monitoring, a low sodium diet program was feasible and in reducing BP.

OBJECTIVES/GOALS: Dietary approach to stop hypertension (DASH) is a proven intervention to treat hypertension. Despite years of research the immediate physiologic response to its implementation was never characterized.This translational trial describes the biological pathway from nutrition through hormons, urine electrolytes and blood pressure reduction. METHODS/STUDY POPULATION: A single center interventional trial. Stage 1 hypertensive otherwise healthy volunteers were admitted for 14-days, transitioning from American style diet to DASH diet. Nutritional habits were assessed with food frequency questionnaires, and menus designed according to the guidelines of the National Heart Blood and Lung Institute (NHBLI) of the National Institute of Health (NIH). Data were collected daily for vital signs, blood and urine. Participants completed two 24-hour ABPM on days 1,10, and two 24-hour urine collections in parallel. We conducted a follow up visit two weeks after discharge. RESULTS/ANTICIPATED RESULTS: 9 volunteers (78% male, 89% Black individuals) completed the protocol. During an inpatient stay, they consumed a mean daily potassium intake of 5.6 g (±0.7g) and 2.6 g (±0.3g) of Sodium. Serum Aldosterone increased from day 0 (mean 8.3, range 2.8-18.9) to day 5 (mean 17.8, range 10.2-27.2) after intervention, and decreased on day 11 (mean 11.5, range 4.8-18.2) despite continuous exposure (p-value=0.002). The urine electrolyte ratio of ([Na]/[K]) decreased from a mean of 3.5 before intervention to 1.16 on day 4, creating a statistically significant slope (p-value<0.001). Blood pressure by 24-hour ABPM decreased by 3.7 mmHg systolic BP and 2.3 mmHg diastolic BP from day 1 to 10 for the entire period, and for measures taken during sleep or awake time, assessed separately. DISCUSSION/SIGNIFICANCE: Shifting from a high-sodium low-potassium diet to the opposite composition leads to serial physiological changes that are governed by aldosterone and result in blood pressure reduction. Urine electrolyte ratio reflects nutritional changes within 4 days of transition and should guide clinicians in assessing lifestyle modification adherence.

OBJECTIVES/GOALS: Trigeminal Neuralgia (TN) is a debilitating neuropathic condition characterized by electric-shock-like pain attacks. TN is considered a clinical diagnosis, and few proposed objective markers exist. This work studies the ability of advanced MRI techniques to diagnose and classify TN. METHODS/STUDY POPULATION: Anatomical MRI data from patients undergoing radiosurgery to treat TN was collected. A custom deep-learning UNet algorithm was trained to segment trigeminal nerves from the pons to the anterior wall of Meckels cave using segments drawn by an expert in neuroanatomy. 108 radiomics features related to nerve shape, voxel intensity, and image texture were extracted from the segmented nerves. A 2 layer neural network was trained to distinguish TN affected nerves from the pain-free contralateral nerves. Feature selection was performed within a cross-validation scheme to prevent model overfitting. Mean model performance over the validation sets was used to estimate model generalizability. RESULTS/ANTICIPATED RESULTS: 134 patients and 268 nerves were included. The average number of years with TN was 8. The average validation set accuracy was 78% [range: 75-80%]. The average validation set sensitivity and specificity were 0.82 [range: 0.79-0.84] and 0.76 [range: 0.70-0.79]. 34% of patients had undergone a prior invasive procedure to treat their TN. To evaluate whether the model detected signal changes relating to the previous treatment, those patients were excluded and the model was retrained on the surgically naive patients. Model performance in a reduced cohort of patients was similar to the model trained on all the patients, with accuracy of 77% [range: 73-82%]. DISCUSSION/SIGNIFICANCE: This study suggests that radiomics features calculated from MRIs of trigeminal nerves correlate with anatomical changes in TN affected nerves. This technique will need to be verified in a larger, more heterogeneous cohort of TN patients with a range of MRI acquisition parameters.

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.

Extensive health inequities exist for persons with criminal-legal involvement in the USA. Researchers, both novice and experienced, are critical in documenting these inequities and implementing programs that address the many health and social problems of this population. However, working with currently or formerly incarcerated persons brings new challenges to researchers that may have not been previously considered as necessary. Because incarcerated persons were systemically exploited by biomedical researchers until reform following the Civil Rights Movement, resulting in their designation as a vulnerable population in the Code of Federal Regulations, enhanced protections are necessary in implementing contemporary research involving incarcerated persons. These enhanced protections can delay or prolong the regulatory approval process, particularly to the novice carceral system researcher, which may discourage some from engaging with this important population. Drawing on the many years of experience working with incarcerated persons accumulated by the Sexual Health Empowerment (S)HE Team at the University of Kansas Medical Center (KUMC), this article offers some concrete steps toward getting started in this work.

OBJECTIVES/GOALS: Osteoarthritis (OA) is a cartilage destroying disease. We are investigating abaloparatide (ABL) activation of parathyroid hormone receptor type 1 (PTH1R), which is expressed by articular chondrocytes in OA. We propose ABL treatment is chondroprotective in murine PTOA via stimulation of matrix production and inhibition of chondrocyte maturation. METHODS/STUDY POPULATION: 16-week-old C57BL/6 male mice received destabilization of the medial meniscus (DMM) surgery to induce knee PTOA. Beginning 2 weeks post-DMM, 40 μg/kg of ABL (or saline) was administered daily via subcutaneous injection and tissues were harvested after 6 weeks of daily injections and 8 weeks after DMM surgery. Harvested joint tissues were used for histological and molecular assessment of OA using three 5 μm thick sagittal sections from each joint, 50 μm apart, cut from the medial compartment of injured knees. Safranin O/Fast Green tissue staining and immunohistochemistry-based detection of type 10 collagen (Col10) and lubricin (Prg4) was performed using standard methods. Histomorphometric quantification of tibial cartilage area and larger hypertrophic-like cells was performed using the Osteomeasure system. RESULTS/ANTICIPATED RESULTS: Safranin O/Fast Green stained sections showed a decreased cartilage loss in DMM joints from ABL-treated versus saline-treated mice. Histomorphometric analysis of total tibial cartilage area revealed preservation of cartilage tissue on the tibial surface. Immunohistochemical analyses showed that upregulation of Col10 in DMM joints was mitigated in the cartilage of ABL-treated mice, and chondrocyte expression of Prg4 was increased in uncalcified cartilage areas in ABL-treated group. The Prg4 finding suggests a matrix anabolic effect that may counter OA cartilage loss. Quantification of chondrocytes in uncalcified and calcified tibial cartilage areas revealed a reduction in the number of larger hypertrophic-like cells in ABL treated mice, suggesting deceleration of hypertrophic differentiation. DISCUSSION/SIGNIFICANCE: Cartilage preservation/regeneration therapies would fill a critical unmet need. We demonstrate that an osteoporosis drug targeting PTH1R decelerates PTOA in mice. ABL treatment was associated with preservation of cartilage, decreased Col10, increased Prg4, and decreased number of large hypertrophic-like chondrocytes in the tibial cartilage.

OBJECTIVES/GOALS: Nutrition plays an imperative role in the management of Duchenne and Becker Muscular Dystrophy, but guidelines for nutrition counseling are absent. This study was designed to gain insight into provider experiences with nutritional services to find solutions for future counseling. METHODS/STUDY POPULATION: In this prospective, observational exploratory study, semi structured interviews were conducted at Certified Duchenne Care Centers (CDCCs) to gain insight on providers experiences with nutritional services and to identify barriers and solutions to nutrition education/care/counseling at CDCCs. Interviews were video recorded and then transcribed for themes. Overarching themes gave insight for a quantitative survey to be sent out, assessing all members on the multidisciplinary team perceptions, confidence, barriers, and solutions to providing nutritional care to Duchenne and Becker patients. RESULTS/ANTICIPATED RESULTS: We anticipate this study will provide novel data and key information from providers regarding nutrition education /care/counseling efforts in the multidisciplinary care of neuromuscular diseases. DISCUSSION/SIGNIFICANCE: Results will demonstrate the need for higher standards and more specific recommendations in nutritional services at CDCCs, while providing a framework for referrals, continuing education opportunities, and increasing providers’ confidence and abilities to provide sound nutritional advice.

OBJECTIVES/GOALS: Large-panel genomic tumor testing (GTT) is a new technology that promises to make cancer treatment more precise. However, patients may have unrealistic expectations of its benefits. The goal of this project is to assess expectations for GTT among cancer patients in community oncology practices. METHODS/STUDY POPULATION: A survey assessing expectations of the benefits of GTT was administered to cancer patients participating in a statewide study of GTT implementation, prior to receiving test results. Descriptive and regression analyses were conducted to assess expectations and the factors associated with these expectations. The study sample (N = 1,139) consisted of patients with a range of cancer types (22% gynecologic, 14% lung, 10% colon, 10% breast,and 46% other malignancies). Mean age was 64 years (standard deviation = 11); 668 (59%) were women; 71% had no college degree; 57% came from households with less than $50,000 US dollars household income; and 73% lived in a rural area. RESULTS/ANTICIPATED RESULTS: Generally, patients had high expectations that they would benefit from GTT (M = 2.81 on 0-4 scale) and positive attitudes toward it (M = 2.98 on 0-4 scale). Patients also had relatively poor knowledge about GTT (48% correct answers on an objective test of GTT knowledge). Greater expectations for GTT were associated with lower knowledge (b = –0.46; p < .001), more positive attitudes (b = 0.40; < .001), and lower education (b = –0.53; < .001). DISCUSSION/SIGNIFICANCE: This research suggests patients have high expectations that they will benefit from GTT, which is associated with low knowledge, positive attitudes, and low education. Interventions may be needed to boost understanding and moderate expectations, particularly for disadvantaged patients.

OBJECTIVES/GOALS: Immunomodulatory drugs (IMiDs) are critical to multiple myeloma (MM) disease control. IMiDs act by inducing Cereblon-dependent degradation of IKZF1 and IKZF3, which leads to IRF4 and MYC downregulation (collectively termed the “Ikaros axis”). We therefore hypothesized that IMiD treatment fails to downregulate the Ikaros axis in IMiD resistant MM. METHODS/STUDY POPULATION: To measure IMiD-induced Ikaros axis downregulation, we designed an intracellular flow cytometry assay that measured relative protein levels of IKZF1, IKZF3, IRF4 and MYC in MM cells following ex vivo treatment with the IMiD Pomalidomide (Pom). We established this assay using Pom-sensitive parental and dose-escalated Pom-resistant MM cell lines before assessing Ikaros axis downregulation in CD38+CD138+ MM cells in patient samples (bone marrow aspirates). To assess the Ikaros axis in the context of MM intratumoral heterogeneity, we used a 35-marker mass cytometry panel to simultaneously characterize MM subpopulations in patient samples. Lastly, we determined ex vivo drug sensitivity in patient samples via flow cytometry. RESULTS/ANTICIPATED RESULTS: Our hypothesis was supported in MM cell lines, as resistant lines showed no IMiD-induced decrease in any Ikaros axis proteins. However, when assessed in patient samples, Pom treatment caused a significant decrease in IKZF1, IKZF3 and IRF4 regardless of IMiD sensitivity. Mass cytometry in patient samples revealed that individual Ikaros axis proteins were differentially expressed between subpopulations. When correlating this with ex vivo Pom sensitivity of MM subpopulations, we observed that low IKZF1 and IKZF3 corresponded to Pom resistance. Interestingly, most of these resistant populations still expressed MYC. We therefore assessed whether IMiD resistant MM was MYC dependent by treating with MYCi975. In 88% (7/8) of patient samples tested, IMiD resistant MM cells were sensitive to MYC inhibition. DISCUSSION/SIGNIFICANCE: While our findings did not support our initial hypothesis, our data suggest a mechanism where MYC expression becomes Ikaros axis independent to drive IMiD resistance, and resistant MM is still dependent on MYC. This suggests targeting MYC directly or indirectly via a mechanism to be determined may be an effective strategy to eradicate IMiD resistant MM.

OBJECTIVES/GOALS: Recent research has attempted to identify diagnostic, prognostic, and predictive biomarkers, however, currently, no biomarkers can accurately diagnose GBC and predict patients prognosis. Using machine learning, we can utilize high-throughput RNA sequencing with clinicopathologic data to develop a predictive tool for GBC prognosis. METHODS/STUDY POPULATION: Current predictive models for GBC outcomes often utilize clinical data only. We aim to build a superior algorithm to predict overall survival in GBC patients with advanced disease, using machine learning approaches to prioritize biomarkers for GBC prognosis. We have identified over 80 fresh frozen GBC tissue samples from Rochester, Minnesota, Daegu, Korea, Vilnius, Lithuania, and Calgary, Canada. We will perform next-generation RNA sequencing on these tissue samples. The patients clinical, pathologic and survival data will be abstracted from the medical record. Random forests, support vector machines, and gradient boosting machines will be applied to train the data. Standard 5-fold cross validation will be used to assess performance of each ML algorithm. RESULTS/ANTICIPATED RESULTS: Our preliminary analysis of next generation RNA sequencing from 18 GBC tissue samples identified recurrent mutations in genes enriched in pathways in cytoskeletal signaling, cell organization, cell movement, extracellular matrix interaction, growth, and proliferation. The top three most significantly altered pathways, actin cytoskeleton signaling, hepatic fibrosis/hepatic stellate cell activation, and epithelial adherens junction signaling, emphasized a molecular metastatic and invasive fingerprint in our patient cohort. This molecular fingerprint is consistent with the previous knowledge of the highly metastatic nature of gallbladder tumors and is also manifested physiologically in the patient cohort. DISCUSSION/SIGNIFICANCE: Integrative analysis of molecular and clinical characterization of GBC has not been fully established, and minimal improvement has been made to the survival of these patients. If overall survival can be better predicted, we can gain a greater understanding of key biomarkers driving the tumor phenotype.

OBJECTIVES/GOALS: Rib fractures are common traumatic thoracic injuries and are associated with high rates of morbidity and mortality. In those age ≥ 65, the rate of these complications double. This study sought to identify the extent to which injury-related predictors influence clinical outcomes in geriatric patients with rib fractures. METHODS/STUDY POPULATION: A retrospective 5-year review was performed of a single Level 1 Trauma center registry. Geriatric patients (≥65 years of age) diagnosed with rib fractures from January 1, 2014 to December 31, 2019 were included. The primary outcome of interest was in-hospital mortality. Secondary outcomes included hospital and intensive care unit length of stay (HLOS and ICU LOS, respectively) and discharge disposition, as a surrogate for loss of independence. Further, subgroup analysis based on number of rib fractures (i.e. <4 and ≥4 rib fractures) was performed. RESULTS/ANTICIPATED RESULTS: 2,134 adult trauma patients were admitted with at least one rib fracture. Of these, 1,037 (49%) were ≥ 65 years old. This cohort had a mean age of 78.6 years old, injury severity score (ISS) of 11.4, HLOS of 7.4 days and 29% required ICU care with mean ICU LOS of 1.9 days. Only 36% were discharged home compared to 64% who were discharged to a care facility and thus had a loss of independence. Overall mortality was 6.3%. Compared to survivors, non-survivors had a higher ISS (19.3 vs. 10.8, p = < 0.0001) and longer ICU LOS (7.1 vs. 6.5 days, p = 0.04). Analysis based on number of rib fractures showed that those with ≥4 rib fractures had significantly higher mortality (8% vs. 4%, p = 0.008), longer HLOS (8.7 vs. 6.1 days, p < 0.0001), longer ICU LOS (2.6 vs. 1.3 days, p < 0.0001), and significantly lower discharge to home (32% vs. 39%, p = 0.02). DISCUSSION/SIGNIFICANCE: To our knowledge, this is the largest single-center study of geriatric patients with rib fractures. In this study, the observed mortality in patients ≥65 years of age was 6.3% which represents a lower mortality rate than historically reported. Despite this, only 36% were able to be discharged directly to home.

OBJECTIVES/GOALS: Neonatal endotracheal tubes (ETTs) are usually uncuffed to avoid subglottic stenosis and other complications, but cuffed ETTs allow better ventilation. Our goal was to detect and control pressure in the cuff below the limit of occluding venous flow to minimize the risk of subglottic stenosis. METHODS/STUDY POPULATION: We designed a pressure sensor to fit on a 2.5 ETT for prototype testing in 8 age adult female rabbits. Eight uncuffed age- and sex- matched rabbits served as control. Study duration was 2 hours during which pressure in the cuff was limited by novel sensor (intervention) or auscultation (control). Anesthesia was maintained with sevoflurane. Ventilation was provided mechanically. Subsequently the tracheae were removed, sectioned crosswise, and compared histologically for mucosal damage. RESULTS/ANTICIPATED RESULTS: Preliminary data demonstrated an almost 30% greater amount of intact mucosa in the intervention group. The sensor also provided data on heart rate and respiratory rate, although this signal was not optimal. After filing an invention disclosure and provisional patent, we are refining our device to include multiple compartments for local control of cuff pressure and applying for a STTR Phase I/II application. DISCUSSION/SIGNIFICANCE: Ventilation in neonates with uncuffed ETTs can be suboptimal due to leak around the tube, but cuffed ETTs pose the threat of subglottic stenosis and other complications. We have designed a prototype cuffed ETT with a sensor to maintain low cuff pressure while preventing leaks and largely avoiding damage to the tracheal mucosa.

OBJECTIVES/GOALS: This presentation outlines a novel approach to evaluating multiple risk factors for the development of dose-limiting toxicities in adolescents and young adults with cancer. This is the first to evaluate biobehavioral predictors originally identified in animal models in clinical human studies. METHODS/STUDY POPULATION: Adolescents and young adults (AYAs) have seen the slowest improvements in cancer survival and have some of the highest rates of dose-limiting mucositis (mouth sores). AYAs receiving chemotherapy with a significant chance of dose-limiting mucositis were recruited for a prospective study. Baseline perceived psychologic stress levels and inflammatory markers were collected at the time of chemotherapy administration and participants completed a daily assessment of mucositis for 14 days following chemotherapy. Logistic regression will be used to evaluate stress and inflammation as predictors of mucositis and Sobels testing will evaluate the role of inflammation as mediators in this relationship. RESULTS/ANTICIPATED RESULTS: We anticipate that, as seen in animal models, stress and inflammation will predict mucositis development. First, we hypothesize that stress levels and inflammatory markers will have a direct correlation and that the level of inflammation at the time of chemotherapy administration will predict mucositis incidence and severity. Through mediation testing, we hypothesize that inflammatory markers will explain a significant amount of the variance in mucositis also explained by stress, identifying inflammation as a mediator in this relationship. In all, we expect that stress and inflammation both predict mucositis development and will be identified as important modifiable factors that can be altered to reduce the risk of toxicity development during cancer therapy. DISCUSSION/SIGNIFICANCE: This work intends to evaluate predictors of chemotherapy-related toxicity development in AYAs with cancer and identify areas of intervention that will reduce toxicity profiles and close the gap in cancer survival for AYAs. Findings are applicable to biomedical, nursing, and psychosocial professionals and will inform future, large clinical studies

OBJECTIVES/GOALS: Almost 8 million Americans live with disability caused by stroke. However, recent advances in stroke rehabilitation are costly and lack resemblance to activities of daily living. The goal of this study was to develop a rehabilitation platform to increase stroke patients paretic limb use using inexpensive virtual reality and exoskeleton devices. METHODS/STUDY POPULATION: We conducted a feasibility study with 2 hemiplegic stroke participants. They reached for targets in a virtual reality environment using both hands. They completed 162 reaches divided into 3 blocks. Following baseline, we used an exoskeleton to provide 50% arm weight compensation to the paretic limb and used wrist weights to provide 50% arm weight resistance to the non-paretic limb. We removed the exoskeleton and wrist weights during the retention block. We used electromyography to approximate muscle activity in the biceps brachii. Relative contribution (RC) was calculated as the displacement of the paretic arm divided by the sum of displacements for both arms. Muscle contribution (MC) was calculated as the root mean square of paretic arm muscle activity divided by the sum of activity for both arms. RESULTS/ANTICIPATED RESULTS: During baseline, RC of the impaired limb was 44% and 48%, and MC of the impaired bicep was 43% and 35% in two mild to moderately impaired patients (Fugl-Meyer Upper Extremity scores of 43 and 37, respectively). During loading, RC increased by 5.6% and 1.1% and MC decreased by 8.3% and 11.8%. These data suggest hemiplegic stroke participants alter limb coordination when our device normalizes muscular output asymmetries between limbs. Importantly, these results closely match data from our previous work in 12 healthy controls, where we found a 2% increase in RC is significantly predicted by a 11% decrease in MC. By collecting more data on stroke patients, we will quantify this tradeoff between coordination and muscle activity modulation, allowing us to optimize the exoskeleton mechanics to maximize paretic limb use. DISCUSSION/SIGNIFICANCE: We demonstrate our platform is well tolerated by mild to moderately impaired stroke patients; this feasibility study forms the basis for low cost at-home technologies for stroke rehabilitation. With further development, clinicians can use our platform to fine-tune the level of limb constraint based on the individual needs of the patient.