OBJECTIVES/SPECIFIC AIMS: N/A. METHODS/STUDY POPULATION: N/A. RESULTS/ANTICIPATED RESULTS: N/A. DISCUSSION/SIGNIFICANCE OF IMPACT: There is an increasing need to foster cross-disciplinary research to address complex problems within healthcare. The Sinai Team-based Translational Education Program: the URM Propeller (STTEP-UP) is a NCATS funded program through the Icahn School of Medicine at Mount Sinai. Its goal is to facilitate URM post-doctoral trainees becoming innovative leaders in clinical and translational research. The program includes a team-based research component, where fellows collaborate on a project. This year, disciplines represented by the four fellows include Cardiology, Psychiatry, Neurology, and Pediatrics. Identifying a clinical question and designing an investigation was facilitated by group brainstorming meetings with program mentors. Fellows designed a project to identify medical testing and prescribing that were not clinically indicated throughout the healthcare system, with the goal of exploring whether an intervention, including provider education, could reduce ordering practices. In addition to regular in-person meetings, a licensed virtual learning environment and free web-based sharing platform were used to foster collaboration. Challenges faced throughout this process, included fellows struggling to find protected time, difficulties accessing broad sets of data across the healthcare system, and overcoming administrative barriers between departments. Strengths of this approach, included fellows learning new research strategies and feeling a deeper sense of commonality with their peers. Overall, this experience supports the idea that cross-disciplinary research improves the collaboration and education of emerging researchers. However, addressing logistical and systems-based barriers may better facilitate this education and research.

OBJECTIVES/SPECIFIC AIMS: Endogenous RT (eRT) is necessary for the function of retrotransposons, elements that replicate via an RNA intermediate. One source of eRT activity is long interspersed elements (LINE). LINEs, of which there are several subgroups (L1, L2, L3), are retrotransposons that regulate cellular growth and gene expression. Given their diverse and important roles, we hypothesized that L1 elements regulate functional responses in megakaryocytes and platelets; a concept not yet examined in the field. METHODS/STUDY POPULATION: To study eRT in human platelets we used RT activity assays, PCR, and Western blot approaches. Furthermore, we used an RT-inhibitor to dissect the function of eRT, analyzed RT-dependent protein synthetic capacity, and immunoprecipitated RNA-DNA hybrids. RNA-DNA hybrids were also detected by means of ICC and automated analysis using CellProfiler software. RNA-DNA hybrids were validated by PCR and eRT regulated synthesis of target proteins was analyzed using autoradiography and Western blot techniques. Platelets from patients with HIV+ were examined in parallel. RESULTS/ANTICIPATED RESULTS: We identified that highly purified, isolated platelets from healthy subjects possess eRT activity. eRT activity was blocked with the non-nucleoside RT inhibitor nevirapine at concentrations within the therapeutic drug range. L1 elements are bicistronic, containing 2 open reading frames (ORFs), ORF1 and ORF2. Thus, we next identified that human platelets express full-length L1 mRNA containing ORF1 and ORF2. In human platelets, eRT activity was localized to L1 protein containing ribonucleo particles. Platelet eRT reverse transcribed exogenous RNAs, a process inhibited by nevirapine, acting in trans using the 3′-UTR of exogenous mRNAs as a template. To dissect the function of eRT in platelets, we next examined cytoskeletal and protein synthetic events in the presence or absence of nevirapine. Inhibition of eRT in isolated platelets led to characteristically beaded platelets in appearance, strongly resembling bone marrow proplatelets. Parallel increases in platelet reactivity were also observed. As these changes occurred over hours, not minutes, we hypothesized that inhibition of eRT would affect platelet protein synthetic events. Consistent with this, RT inhibition resulted in upregulation of global platelet protein synthesis. We validated upregulation of the synthesis of specific proteins (mitofilin, p-selectin, and L26—a component of the 60S ribosomal subunit essential for mRNA translation). RNA-DNA hybrids, noncanonical nucleic acid structures that regulate gene expression, are enriched in regions where L1 is abundant. RNA-DNA hybrids were present in platelets and expression confirmed via differential digestion of RNAs (eg, with RNase A and RNAse I). Next-generation sequencing of pulled down (eg, immunoprecipitated) platelet RNA-DNA hybrids identified numerous differentially expressed transcripts and we focused on MAP1LC3B (LC3B), a primary regulator of autophagy. Hybrid sequencing results for LC3B were validated using qPCR and we confirmed that LC3B RNA binds to L1-encoded RNA binding protein. Platelets treated with nevirapine had increased total LC3B protein expression. As RT inhibition is an important mechanism to control HIV infection, we examined platelet morphology, activation, and LC3B expression in platelets from HIV+ subjects treated with nevirapine. HIV+ patients treated with RT inhibitors had higher numbers of platelets that were beaded in appearance at baseline, increased platelet reactivity, and differential LC3B expression compared with healthy controls. DISCUSSION/SIGNIFICANCE OF IMPACT: Taken together, these results demonstrate that platelets possess eRT activity that regulates platelet morphology, platelet hyperreactivity, and protein synthetic events. We postulate that eRT activity in platelets may be a new post-transcriptional regulatory checkpoint. Moreover, our findings have implications in HIV+ patients treated with RT inhibitors, where off-target effects may contribute to platelet activation and an increased risk of thrombosis.

OBJECTIVES/GOALS: By establishing a youth-centric web-app as a central hub of information and inspiration in an attempt to engage a young demographic, this project aims to increase community awareness and reduce misconceptions surrounding clinical trials, in hopes of fairly representing marginalized communities among future clinical trial participants. METHODS/STUDY POPULATION: We designed a children’s web-app to host a collection of child-friendly educational materials (such as picture books, games, and age-appropriate articles about advances in clinical research) explaining clinical research and its process. An emphasis was put on ensuring the web-app and its contents were understandable and appealing to children. The effectiveness of this tool will be tested through a focus group study. Children ages 7-10 will be given a preliminary survey measuring their knowledge and opinions about clinical research, and then given time to explore the web-app. Afterwards, they will be given a secondary survey to gauge their acquired knowledge from the website and asked about their opinion on the design and usability of the web-app and its materials, as well as how likely they were to revisit the site. RESULTS/ANTICIPATED RESULTS: We anticipate a very positive response from the children regarding the design and usability of the web-app and its materials. By using an adolescent-focused design methodology at every step of the design process, we will ensure that all materials are attractive and engaging to our younger target audience. Exposing children to accessible information about clinical trials at a young age allows us to build their trust in the research process prior to the possible internalization and acceptance of cultural misconceptions. Over time, we hope to see a change in attitudes toward clinical research as well as increased participation, whether from under-represented groups or a younger demographic, and positively contribute to T3 and onwards in the translational continuum. DISCUSSION/SIGNIFICANCE: In a rapidly changing world, the best approach to making change is through targeting the younger demographic, the leaders of tomorrow. Our project will allow adolescents to foster a more well-rounded opinion of clinical research, increasing their participation and better paving a more positively received future for translational science as a whole.

OBJECTIVES/GOALS: Young women (18 – 45 years of age) with breast cancer have complex medical and psychosocial needs. Educational materials are often used as tools in patient-centered communication. However, these materials disseminate complex health information in print-heavy formats and can be difficult to understand for women with varying health literacy levels. METHODS/STUDY POPULATION: In the first phase of this study, the principal investigator (PI) will recruit 40 diverse women to participate in four focus groups (FG) to explore the perceived usefulness of the most frequently used cancer educational materials. The PI will also obtain demographics and heath literacy levels of the FG participants using the Newest Vital Sign. In the second phase, the PI will assess the literacy demands of the ten most frequently used cancer educational print materials and five most frequently used websites described by the FG participants. The perceptions of the usefulness of materials and the literacy demands will then be used to appraise the effectiveness of materials within patient-centered cancer communication. RESULTS/ANTICIPATED RESULTS: Results from this study will provide a patient-centered blueprint that will be used to design more effective educational materials that treatment centers can incorporate into their patient-centered cancer communication process. The next step of this research will be to determine providers’ perceptions of cancer education materials used to exchange information within the patient-centered communication process. This will complement the patient findings and inform the development of the provider aspect of a communication intervention centered on designing educational materials for women with various health literacy levels within the patient-centered cancer communication process. DISCUSSION/SIGNIFICANCE OF IMPACT: Detecting the usefulness of cancer educational materials, as perceived by young women with breast cancer, is foundational to developing communication interventions that improve cancer outcomes. This study will identify how materials can be improved in the critical informational-exchange component of the patient-communication process.

OBJECTIVES/SPECIFIC AIMS: The overall goal of this project is to determine whether timing of seasonal influenza vaccination affects the severity of illness in vaccinated individuals who are hospitalized with influenza. This will be assessed with the following aims: 1. To determine whether differences in demographic and clinical characteristics exist among patients with short duration between seasonal influenza vaccination and influenza-related hospitalization and those with longer duration. 2. To determine whether time between seasonal influenza vaccination and hospitalization is associated with the duration of influenza-related hospitalization. 3. To determine whether time between seasonal influenza vaccination and hospitalization is associated with the rate of influenza-related ICU admission among patients hospitalized with influenza. 4. To determine whether time between seasonal influenza vaccination and hospitalization is associated with the rate of influenza-related death among adults hospitalized with influenza. METHODS/STUDY POPULATION: The Influenza Hospitalization Surveillance Network (FluSurv-NET) is a surveillance platform of influenza-related hospitalizations through the CDC Emerging Infections Program (EIP). FluSurv-NET conducts active surveillance for influenza-related hospitalizations of both children and adults in selected counties in California, Colorado, Connecticut, Georgia, Maryland, Michigan, Minnesota, Ohio, Oregon, New Mexico, New York, Tennessee, and Utah with a total catchment population of over 27 million people (~9% of the US population). Using this platform, we will retrospectively evaluate four influenza seasons using FluSurv-NET data to look at the timing of influenza vaccination and severity of illness among patients with influenza-related hospitalization. We will conduct a multivariate analysis to assess for differences in severe outcomes including duration of hospitalization, ICU admission, and death among patients with varying lengths of time between influenza vaccination and influenza-related hospitalization. Separate analyses will be performed among different age groups and influenza type/subtypes, as well as specific seasons as a surrogate for most common circulating strain. RESULTS/ANTICIPATED RESULTS: We hypothesize that patients with chronic medical conditions and those at the extremes of age will have a longer duration between vaccination and hospitalization as they are more likely to get vaccinated earlier. We also hypothesize that patients with longer duration between seasonal influenza vaccination and hospitalization will have a longer duration of hospitalization and a higher rate of other severe outcomes (e.g., ICU admission, death). Such data would suggest that immune protection wanes during the influenza season. DISCUSSION/SIGNIFICANCE OF IMPACT: Limited data suggest that vaccine-induced influenza immunity may wane during the influenza season. It is not known whether the impact of influenza vaccination upon severity of disease might wane with increasing time between vaccination and influenza infection. In contrast to many previous studies evaluating vaccine effectiveness which have assessed medically-attended influenza illness as a primary outcome, our dataset is a large cohort of hospitalized patients which allows us to assess rare yet critical outcomes such as ICU admission and death. This study will also have a substantially larger amount of pediatric data than previous studies, which will provide the opportunity to determine whether timing of vaccination affects children and adults differently. Improving our understanding of whether influenza vaccine-induced protection might wane over time could ultimately impact U.S. influenza vaccination policy resulting in decreased morbidity and mortality attributed to influenza each season.

ABSTRACT IMPACT: This work will accelerate the translation of post stroke rehabilitation devices from the research lab to clinic use. OBJECTIVES/GOALS: Rehabilitation device efficacy alone does not lead to adoption into clinical practice. The objective of this work was to increase understanding of the landscape for clinical adoption of post-stroke physical rehabilitation devices. METHODS/STUDY POPULATION: We conducted interviews with 107 stakeholders including patients who have had strokes, rehab directors, and physical/occupational therapists to understand their viewpoints for adopting new rehabilitation devices. To contribute to previous literature, interviews were analyzed qualitatively using direct content analysis to provide more specific details about the most appropriate adoption settings, specific roles for stakeholders, and drivers for all stakeholders involved in the adoption process. RESULTS/ANTICIPATED RESULTS: Unique to this work, care settings in which therapy goals are best aligned for restorative devices were found to be outpatient rehabilitation, followed by inpatient rehabilitation. Therapists are the major influencers for adoption because they typically introduce new rehabilitation devices to patients for both clinic and home use. We also learned therapists’ utilization rate of a rehabilitation device influences a rehabilitation director’s decision to acquire the device for facility use. Additionally, device setup in <7 minutes will allow for increased use without reducing therapist productivity. DISCUSSION/SIGNIFICANCE OF FINDINGS: Rehabilitation device development should consider the best settings to first introduce the device, roles of each stakeholder, and drivers that influence each stakeholder to accelerate successful adoption of the developed device.

OBJECTIVES/SPECIFIC AIMS: To review the multiple differences between traditional research design and on the ground pragmatic trials. To review two pragmatic projects, identify core assumptions and to contrast assumptions with the reality of conducting T3 and T4 research. METHODS/STUDY POPULATION: Observational mixed methods multi trial review of large multi site implementations. RESULTS/ANTICIPATED RESULTS: The complexities of implementation on the ground were consistently greater than anticipated and required changing assumptions and research design elements. DISCUSSION/SIGNIFICANCE OF IMPACT: Research findings are tremendously influenced by design and design implementation decisions. Anticipating the scope and breadth of the challenges will assist potential of successful implementation.

OBJECTIVES/SPECIFIC AIMS: (1) Correlate PBX1 mRNA expression as measured by RNAScope in situ hybridization, at an RNA number/cell measurement, Versus by RT-qPCR by the ddCt method. (2) Validate PBX1 mRNA expression in a second independent cohort of neuroblastoma tumor samples, and correlate with patient outcomes. We expect that PBX1 expression will correlate whether detected by RNAScope or by RT-qPCR. This work has the promise of validating a novel biomarker of disease severity, and for clinical translation as the RNAscope technology has been CLIA-certified for clinical use for other genes. METHODS/STUDY POPULATION: Primary neuroblastoma tumor samples were acquired through the Children’s Oncology Group Tumor Bank, The Cooperative Human Tissue Network Tumor bank, and the Westmeade Tumor Bank (Westmeade, Australia), with patient outcomes annotated but sequestered until experiments are completed. RT-qPCR is performed using 1 μg total RNA isolated from each sample by Nucleospin RNA kit (Clontech), reverse transcribed by SuperScript VILO (ThermoFisher Scientific) and amplified using KiCqSTART SYBR Green qPCR mix (Sigma Aldrich). RNAScope was performed on sections of fresh frozen tumor, in triplicate, per manufacturer protocol (ACDBio) using company-designed probes. Statistical analyses performed using GraphPad Prism5. RESULTS/ANTICIPATED RESULTS: PBX1 mRNA expression as measured RNAScope correlated well with matched RT-qPCR values, with most PBX1 transcripts identified within the malignant cells and not in tumor stroma. Correlation with patient outcomes is ongoing (expected to be available at the time of presentation), but as the RNAScope values correlate with R>0.9 with RT-qPCR values, we expect good correlation with outcomes in our primary data set and matching validation set. DISCUSSION/SIGNIFICANCE OF IMPACT: PBX1 mRNA expression is an accurate prognostic biomarker of outcome in low and intermediate-risk neuroblastoma, and testing on an additional validation set is planned based on thresholds established by RNAScope. RNAScope is a method readily translatable to clinical use and its inclusion in future clinical trials will be further studied. It provides an additional benefit that concomitant immunohistochemistry can also be performed. Analysis of high-risk neuroblastomas for responsiveness to retinoic acid based on PBX1 expression is planned.

OBJECTIVES/GOALS: This study examined youth tobacco use, disaggregated by sexual and gender minority (SGM) identity and race, in Massachusetts before and after the state implemented a flavored tobacco restriction. We assessed if the policy differentially impacted groups that have had higher rates of flavored tobacco use (i.e., SGM and African Americans [AAs]). METHODS/STUDY POPULATION: Data for this analysis came from the 2019 and 2021 Massachusetts Youth Risk Behavior Survey (YRBS), a biennial, national survey conducted among high school students, provided by the Massachusetts Department of Elementary and Secondary Education. Changes in current use of cigarettes and e-cigarettes between 2019 and 2021 were examined for the entire sample and by SGM identity and race/ethnicity. Current cigarette use and current e-cigarette use were defined as reporting any use of the product in the past 30 days. We received confirmation from the IRB that because the data are de-identified and available to the public, this research is considered Not Human Subjects Research. RESULTS/ANTICIPATED RESULTS: Between 2019 and 2021, current cigarette use and current e-cigarette use decreased for the entire sample (3.78% to 2.79% and 27.69% to 15.74%, respectively). Decreases were also observed after disaggregating results, but smaller changes were observed among minoritized groups (i.e., SGM and AAs), particularly for e-cigarettes. Current e-cigarette use decreased 25.56% among individuals identifying as SGM (28.14% to 20.95%) compared to a 49.33% decrease among non-SGM individuals (27.63% to 14.0%). Among all races, AAs had the lowest prevalence of current e-cigarette use in 2019 (15.10%), but also saw the lowest percentage decrease (17.68%). Among whites, current e-cigarette use decreased 45.75% from 32.33% in 2019 to 17.54% in 2021. DISCUSSION/SIGNIFICANCE: After implementation of Massachusetts’ flavored tobacco restriction, current cigarette and e-cigarette use declined among Massachusetts youth overall and among groups that have been most affected by flavored tobacco. However, minoritized groups (i.e., SGMs, AAs) had lower percentage decreases compared to non-minoritized groups.

ABSTRACT IMPACT: This study informs how substance use treatment programs responded to the COVID-19 pandemic, and highlights implication for future translational research and practice. OBJECTIVES/GOALS: The COVID-19 pandemic rapidly changed how substance use disorder (SUD) treatment services are organized and provided. This study examined what changes SUD treatment programs in Arkansas implemented (e.g., guidelines, technologies), and what factors influenced their ability to implement and sustain these changes. METHODS/STUDY POPULATION: Between May and August 2020, we conducted semi-structured phone interviews with 29 leaders (administrative and/or clinical leaders) at 21 residential and outpatient SUD treatment programs throughout Arkansas (i.e., in all five Arkansas public health regions). Interviews were based on the Consolidated Framework for Implementation Research and focused on what changes programs were implementing in response to the COVID-19 pandemic, barriers and facilitators to implementation, and recommendations for future. The interviews were on average about 30 minutes long, and we provided no participant compensation. Interviews were recorded and transcribed verbatim, then thematically analyzed. RESULTS/ANTICIPATED RESULTS: Programs implemented similar infection control practices: screening at entry, masks, hand hygiene, and social distancing. Residential programs stopped outside visitations and some capped admissions; outpatient programs stopped group sessions and switched most services to telehealth. Key facilitators included grants/loans (e.g., salaries), looser regulatory restrictions (e.g., telehealth), and good coordination with other organizations (e.g., state agencies). Key barriers included limited access to supplies (e.g., masks), no rapid testing (particularly for residential care), limited capacity for social distancing, and negative employee and client responses (e.g., anxiety). Key recommendations include better access to supplies and testing, telehealth continuation and better communication. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study provides an insight into how SUD programs responded to the COVID-19 pandemic and what the ‘new normal’ is. This can inform D&I studies conducted in SUD settings, including studies examining what implementation strategies can help sustain these changes, or studies of other practices implemented during or after the pandemic.

OBJECTIVES/GOALS: This study examines health provider andcaregiver influences on adolescent dual prevention strategies, or the use of condoms and another form of contraception, to informa clinically focused triadic intervention, involving caregivers, adolescents aged 15-17, and health providers. METHODS/STUDY POPULATION: Data for the 2021 Teen and Parent Surveywere two online, cross-sectional surveys, a national sample of adolescents aged 15-19, and a survey of caregivers of 15–17-year-old adolescents. Data were matched to create a dyadic dataset (n=273). Drawing from the Actor-Partner-Dependance Model we will conduct a secondary retrospective analysis, specifically cross-sectional univariate, bivariate, and multivariate logistic regression analyses on sets of influences around contraception and sexual health: communication with parents and health providers, information delivery of sexual health, condom attitudes and self-efficacy around preventative behaviors. RESULTS/ANTICIPATED RESULTS: In preliminary unadjusted analyses, 91% of the sample were cis-gender females (n=249), of which 32% (n=87) had sexual contact with someone who could get them pregnant. In the past, 35% (n=86) discussed birth control pills and 9% (n=24) discussed long-acting contraception with a health provider. In the last health visit, 29% (n=72) discussed STI prevention. Caregivers discussed sexual decision-making (49%, n=144), how to prevent pregnancy (62%, n=169), and how to prevent STIs (55%, 151) at least once in the past year. At last sex (n=49) most used condoms (47%, n=23), followed by birth control pills (33%, n=16), and withdrawal (14%, n=7). Additional predictors and adjusted analyses will be further examined. DISCUSSION/SIGNIFICANCE: Dual prevention strategies can be influenced by caregivers and health providers, but they are contingent on communication. Triadic interventions may consider involving both caregiver and health provider communication around sexual health prevention.

OBJECTIVES/SPECIFIC AIMS: To further elucidate the role of estrogen receptor β (ER-β) in the early endometriotic lesion attachment. METHODS/STUDY POPULATION: EECs were immortalized using a telomerase vector. Immortalized cells and parental cells were characterized by genotyping, and expression of ER-β as well as other epithelial cell markers. ER-β was knocked-down in immortalized EECs using lentivirus-mediated shRNA transduction. ER-β knockdown was confirmed by RT-qPCR and Western analysis. EEC cells with or without ER-β knockdown were used to assess their attachment to PMCs in an established in vitro assay (Lucidi, 2005). Results were analyzed with Student t-test. RESULTS/ANTICIPATED RESULTS: Genotyping using karyotype assay confirmed a normal chromosomal profile. Also positive staining for cytokeratin and lack of any staining with vimentin confirms the epithelial origin of these cells. ER-β knockdown has a significant decrease in attachment compared to control (p=0.02). DISCUSSION/SIGNIFICANCE OF IMPACT: Primary and immortalized cells were 46XX, cytokeratin positive, and vimentin negative confirming their epithelial origin. ER-β knockdown has a significant decrease in attachment compared with control.

OBJECTIVES/GOALS: (1) Determine nurse (age, education level, years of experience, ID education/training, contact with people with ID, communication apprehension, beliefs about patient quality of life), and nursing unit (teamwork, staffing and resources, person-centered care) characteristics that are associated with and predictive of nurses’ attitudes, positive emotions, and negative emotions toward caring for adults with ID. (2) Explore nurses’ perspectives of perceived barriers and facilitators to providing nursing care to hospitalized persons with ID and medical comorbidity, and how nursing care differs when caring for a person with ID. METHODS/STUDY POPULATION: This mixed methods nested analysis will employ an internet survey of medical-surgical registered nurses to collect nurses’ attitudes and emotions toward caring for hospitalized persons with ID and medical comorbidity, nurse characteristics, and nursing unit characteristics. We intend to recruit 150 medical surgical nurses currently practicing in the United States via email invitation to the membership of the Academy of Medical Surgical Nurses. Purposeful maximum variation sampling will be used to invite a subset of respondents for qualitative, semi-structured telephone interviews to elicit barriers and facilitators to nursing care of persons with ID and how nursing care differs when caring for persons with ID. RESULTS/ANTICIPATED RESULTS: We hypothesize that lower nurse education level, fewer years of experience, less ID education/training, lower amount of contact with people with ID, increased communication apprehension, and lower beliefs about the quality of life of persons with ID will be associated with negative nurse attitudes and emotions toward caring for people with ID. Further, we hypothesize that lower levels of nursing unit teamwork, staffing and resources, and person-centered care practices will be associated with negative nurse attitudes and emotions toward caring for people with ID. DISCUSSION/SIGNIFICANCE OF IMPACT: The proposed research is an important first step in determining potential nurse and nursing unit factors influencing nurses’ attitudes toward caring for people with ID. It will lead to targeted interventions to enhance nursing care quality and reduce hospital-associated healthcare disparities among people hospitalized with intellectual disabilities and medical comorbidities.

OBJECTIVES/GOALS: The objective of my study is to test my overall hypothesis that CDK4/6 inhibitor-induced cellular senescence has long-lasting consequences on the tumor microenvironment that affect tumor growth and disease progression. METHODS/STUDY POPULATION: There is a lack of mechanistic understanding of the crosstalk of drug effects on different cellular pathways. One less-studied consequence of CDK4/6 inhibitors (CDKI) is their ability to induce cellular senescence in the non-malignant host cells (“stroma”), which causes secretion of a plethora of proteins that have lasting effects on the tumor microenvironment. Stromal cells are known to be able to enter senescence and promote a state of chronic inflammation that contributes to disease progression. I propose to study the stromal contribution to the tumor microenvironment and how this affects tumor growth and disease progression by using genetically engineered mouse models of breast cancer. RESULTS/ANTICIPATED RESULTS: We have found that palbociclib, a CDKI, inhibited growth and induced senescence of breast cancer cell lines xenografted into mice, and that while most on-target effects of palbociclib were reversed after treatment cessation, there was long-lasting down-regulation of interferon-γ and inflammatory response signaling pathways in the mouse host stroma that persisted after cessation of palbociclib treatment. In syngeneic models, we have found that palbociclib treatment influenced migration of T cells into CDKI-resistant tumors. DISCUSSION/SIGNIFICANCE: These studies will shed light on how senescence-inducing anticancer therapies, such as CDKI, affect tumor growth and disease progression. My studies will help elucidate new therapeutic avenues in combination with CDKI to combat therapeutic resistance in advanced breast cancer.

OBJECTIVES/SPECIFIC AIMS: Macrolides, linezolid, imipenem-cilastatin, fluoroquinolones, penicillin combinations, and ceftriaxone are known to be associated with Torsade de pointes/QT prolongation (TdP/QTP). Other antibiotics may also lead to TdP/QTP, but no study has systemically compared TdP/QTP risks of different antibiotics using recent data. Therefore, the objective of this study was to evaluate the association between TdP/QTP and antibiotics in recent years using the FDA Adverse Event Report System (FAERS). METHODS/STUDY POPULATION: FAERS reports from January 1, 2015 to December 31, 2017 were analyzed. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify TdP/QTP cases. We calculated the Reporting Odds Ratios (RORs) and corresponding 95% confidence intervals (95%CI) for the association between antibiotics and TdP/QTP. An association was considered to be statistically significant when the lower limit of the 95%CI was greater than 1. RESULTS/ANTICIPATED RESULTS: A total of 2,042,801 reports (including 5,221 TdP/QTP reports) were considered, after inclusion criteria were applied. Macrolides had the greatest proportion of TdP/QTP reports, representing 2.9% of all macrolide reports. TdP/QTP RORs (95%CI) for the antibiotics were (in descending order): macrolides 11.73 (9.74-14.12), linezolid 9.39 (6.45-13.68), amikacin 8.94 (4.22-18.92), imipenem-cilastatin 5.01 (2.38-10.56), fluoroquinolones 4.67 (3.96-5.52), penicillin combinations 3.52 (2.56-4.86), cephalosporins 1.90 (1.14-3.16), metronidazole 1.49 (0.74-2.99), vancomycin 1.26 (0.70-2.28), clindamycin 0.83 (0.27-2.58), trimethoprim-sulfamethoxazole 0.82 (0.31-2.18), and amoxicillin 0.57 (0.18-1.78). DISCUSSION/SIGNIFICANCE OF IMPACT: This study confirms prior evidence for TdP-QTP risks with macrolides, linezolid, imipenem-cilastatin, fluoroquinolones, penicillin combinations, and cephalosporins. This study provides new evidence for TdP-QTP risks with amikacin. Macrolides had the highest TdP/QTP ROR among the antibiotics evaluated in this study.

OBJECTIVES/GOALS: The purpose of this mixed methods project was to gain a comprehensive understanding and generate data on factors, including stress and inflammatory biomarkers, that may negatively impact glycemic levels in children aged 8-12 years with type 1 diabetes (T1D) from underrepresented backgrounds. METHODS/STUDY POPULATION: This study employed a two-phase sequential QUAN -> qual mixed methods design. Children and their parents were recruited from a pediatric endocrinology clinic in the southeastern United States. In phase 1 (n=34), we used quantitative methods to measure perceived stress, diabetes distress, cortisol, inflammation (IL-1b, IL-2; IL-6; IL-8; TNF-a; CRP), and glycemic level (HbA1c). Both children and their parent/guardian completed surveys, and children provided salivary and blood samples to measure cortisol and inflammatory markers. Phase 2 qualitative interviews in a subset (n=20) of children and parent/guardians from phase 1 are ongoing; preliminary findings will be included in the presentation. RESULTS/ANTICIPATED RESULTS: Mean age of children was 10.47 (sd=1.44), 67.6% were male, and 41.2% were black. HbA1c ranged from 6.8%-15% and only 2 (5.8%) children met ADA recommendations for HbA1c of 7% or less. HbA1c was associated with child reports of perceived stress (r = .403, p < .05), but not parent reports of child perceived stress (r = -.011, p > .05). Parent reports of perceived stress and diabetes distress in children were not significantly associated with child self-report of perceived stress (r = .11, p > .05) or diabetes distress (r = .018, p > .05). Exploratory models with PROCESS suggest that cortisol slope and IL-8 moderate the relationship between child’s perceived stress and glycemic control. DISCUSSION/SIGNIFICANCE: Stressors are emerging that are unique to this population and may help highlight disparities in care. While the study is ongoing, findings may help health professionals identify and mitigate stressors in children with T1D to help maintain optimal glycemic levels.