Objectives/Goals: This research aims to identify genetic alterations influencing congenital anomalies of the kidney and urinary tract (CAKUT) and bridge a fundamental gap in understanding the cellular mechanisms underlying kidney development, with the long-term goal of enhancing treatments for congenital renal anomalies. Methods/Study Population: We will use a loss-of-function approach in combination with immunofluorescent microscopy techniques to determine the influence of Dnmbp perturbation on Daam1 localization, actin assembly, and junctional turnover. Additionally, to establish a foundation for delineating the molecular mechanism of DNMBP during kidney development, we will utilize clinical whole exome sequencing data to identify human DNMBP mutations associated with urogenital anomalies. Furthermore, we will determine whether human DNMBP mutations linked to CAKUT lead to disruptions in nephron development through loss-of-function rescue experiments in Xenopus. Results/Anticipated Results: Here, we evaluate the dynamics of Dnmbp-mediated transport of Daam1 within the developing kidney and show preliminary data suggesting that Dnmbp and Daam1 directly interact to promote adhesive contact formation between nephron progenitor cells. Furthermore, we propose a model in which Dnmbp functions as a critical regulator of epithelial tissue morphogenesis and provides a functional link between the dynamic processes of actin cytoskeleton regulation, intracellular adhesion, and vesicular transport. Future studies will determine whether Dnmbp interaction with Daam1 facilitates junctional actin assembly by directing Daam1 to cell–cell contact sites via Dnmbp-associated vesicle targeting, enhancing our understanding of the cellular mechanisms influencing tubule morphogenesis. Discussion/Significance of Impact: This research will establish a previously unknown role for DNMBP in kidney development and provide a comprehensive understanding of the impacts of simultaneously regulating vesicular transport and actin dynamics in nephrogenesis.

Despite thousands of individuals entering the illegal wildlife trade each year, assessments of pangolin populations are largely non-existent, even in areas with high exploitation and limited personnel and field equipment. Although pangolins have unique keratin-based scales, there is no universal scale-marking method for individuals despite some pangolin conservation programmes utilizing marking for reference and cataloguing. Each programme currently establishes and manages its own system, resulting in inconsistencies and limiting data sharing. To facilitate pangolin monitoring and research, we developed a standardized method for assigning individual identification numbers, which we call the Pangolin Universal Notching System. This system is neither resource nor training intensive, which could facilitate its adoption and implementation globally. Its application could help to address knowledge gaps in pangolin ageing, reproduction, survivorship, migration and local trafficking patterns, and could be used in combination with other tagging techniques for research on pangolin biology.

This study identified 26 late invasive primary surgical site infection (IP-SSI) within 4–12 months of transplantation among 2073 SOT recipients at Duke University Hospital over the period 2015–2019. Thoracic organ transplants accounted for 25 late IP-SSI. Surveillance for late IP-SSI should be maintained for at least one year following transplant.

Boduch-Grabka and Lev-Ari (2021) showed that so-called “native” British-English speakers judged statements produced by Polish-accented English speakers as less likely to be true than statements produced by “native” speakers and that prior exposure to Polish-accented English speech modulates this effect. Given the real-world consequences of this study, as well as our commitment to assessing and mitigating linguistic biases, we conducted a close replication, extending the work by collecting additional information about participants’ explicit biases towards Polish migrants in the UK. We did not reproduce the original pattern of results, observing no effect of speaker accent or exposure on comprehension or veracity. In addition, the measure of explicit bias did not predict differential veracity ratings for Polish- and British-accented speech. Although the current pattern of results differs from that of the original study, our finding that neither comprehension nor veracity were impacted by accent or exposure condition is not inconsistent with the Boduch-Grabka and Lev-Ari (2021) processing difficulty account of the accent-based veracity judgment effect. We explore possible explanations for the lack of replication and future directions for this work.

Background: Patients requiring mechanical circulatory support (MCS) during episodes of cardiogenic shock are at risk for hospital-acquired bloodstream infection (HABSI). Clinically MCS devices include extracorporeal membrane oxygenation (ECMO) devices, durable and temporary left ventricular-assist devices (VADs), and intra-aortic balloon pumps (IABPs). However, the MCS exclusion to the NHSN central-line–associated bloodstream infection (CLABSI) surveillance rules in 2018 did not include IABP as a qualifying device. We have described utilization and incidence of primary HABSI (pHABSI) in our patients requiring MCS. Methods: The setting for this study was 9 cardiothoracic and heart failure intensive care units with 131 total beds at the Cleveland Clinic Main Campus. Surveillance for HABSI to include determination of CLABSI was performed prospectively. MCS-associated pHABSI were patients who had ECMO, LVAD, or IABP present for >2 calendar days with device in place on the date of infection or removed the day before. A patient with 2 device types at time of infection was counted as a pHABSI for both groups. Patient, device, and MCS days were extracted from an electronic database. Non-MCS patient days were calculated as the difference between total patient days and total MCS days. The incidence of ECMO-, VAD-, and IABP-associated pHABSI were compared to each other and to non–MCS-associated pHABSI using OpenEpi version 3.01 software. Results: Surveillance results are shown in Table 1. During the observation period, there were 221 pHABSIs and 139,013 patient days. Moreover, 67 pHABSIs were associated with an MCS device over 17,044 total MCS days: 43 ECMO days, 18 VAD days, and 13 IABP days. Also, 9 patients had >1 type of eligible device and 7 (39%) of the IABP-associated pHABSIs were CLABSIs.

The cumulative incidences of pHABSI associated with ECMO, VAD, and IABP were 5.68, 4.59, and 2.34 per 1,000 MCS days, respectively. The incidence of IABP pHABSI was not significantly different from VAD pHABSI (P = .06), but it was different from ECMO pHABSI (P < .01). The pHABSI rate for non-MCS days was 1.26 per 1,000 patient days. Conclusions: In our patients requiring MCS, the risk of pHABSI associated with IABP was significantly greater than in patients without MCS and was similar to patients with VAD. MCS of all types should be considered a risk for HABSI in patients with cardiogenic shock beyond the presence of a central line. Protocols to further prevent HABSI morbidity in IABP patients are needed.

Disclosure: None

This study investigated, and discusses the integration of, the shift-and-persist (SAP) and skin-deep resilience (SDR) theories. The SAP theory states that the combination of shifting (adjusting oneself to stressful situations through strategies like emotion regulation) and persisting (enduring adversity with strength by finding meaning and maintaining optimism) will be beneficial to physical health in children experiencing adversity. The SDR theory states that high striving/self-control will be beneficial to mental health but detrimental to physical health among those confronting adversity. This study investigated 308 children ages 8–17 experiencing the adversity of a chronic illness (asthma). SAP and SDR (striving/self-control) were assessed via questionnaires, and physical health (asthma symptoms, inflammatory profiles), mental health (anxiety/depression, emotional functioning), and behavioral (medication adherence, activity limitations, collaborative relationships with providers) outcomes were measured cross-sectionally. SAP was associated with better physical health, whereas SDR was associated with worse physical health. Both were associated with better mental health. Only SDR was associated with better behavioral outcomes. Implications of findings and discussion of how to integrate these theories are provided. We suggest that future interventions might seek to cultivate both SAP and SDR to promote overall better health and well-being across multiple domains in children experiencing adversity.

OBJECTIVES/GOALS: Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors that are driven by populations of cancer stem cells (CSCs). In this study, we perform an epigenetic-focused functional genomics screen in GBM organoids and identify WDR5 as an essential epigenetic regulator in the SOX2-enriched, therapy resistant cancer stem cell niche. METHODS/STUDY POPULATION: Despite their importance for tumor growth, few molecular mechanisms critical for CSC population maintenance have been exploited for therapeutic development. We developed a spatially resolved loss-of-function screen in GBM patient-derived organoids to identify essential epigenetic regulators in the SOX2-enriched, therapy resistant niche. Our niche-specific screens identified WDR5, an H3K4 histone methyltransferase responsible for activating specific gene expression, as indispensable for GBM CSC growth and survival. RESULTS/ANTICIPATED RESULTS: In GBM CSC models, WDR5 inhibitors blocked WRAD complex assembly and reduced H3K4 trimethylation and expression of genes involved in CSC-relevant oncogenic pathways. H3K4me3 peaks lost with WDR5 inhibitor treatment occurred disproportionally on POU transcription factor motifs, required for stem cell maintenance and including the POU5F1(OCT4)::SOX2 motif. We incorporated a SOX2/OCT4 motif driven GFP reporter system into our CSC cell models and found that WDR5 inhibitor treatment resulted in dose-dependent silencing of stem cell reporter activity. Further, WDR5 inhibitor treatment altered the stem cell state, disrupting CSC in vitro growth and self-renewal as well as in vivo tumor growth. DISCUSSION/SIGNIFICANCE: Our results unveiled the role of WDR5 in maintaining the CSC state in GBM and provide a rationale for therapeutic development of WDR5 inhibitors for GBM and other advanced cancers. This conceptual and experimental framework can be applied to many cancers, and can unmask unique microenvironmental biology and rationally designed combination therapies.

Background. Primary care providers play a key role in screening for tobacco use and assessing desire to quit. Tobacco treatment specialists (TTS) are certified in helping patients who desire tobacco cessation. A primary care nurse practitioner within one Midwestern healthcare organization obtained TTS certification and integrated specialized tobacco cessation visits within a primary care clinic from February 2021 to February 2022. Purpose. To determine the efficiency and effectiveness of an integrated TTS-certified nurse practitioner (TTS-NP) in a primary care setting 1-year postimplementation. Method. This program evaluation utilized retrospective electronic health record review and included thirty-three patients. The logic model served as a framework to define efficiency and effectiveness. Results. Patients were referred by a provider (57.6%), nurse (15.2%), or self (27.3). Patients opted for in-person initial visits (81.8%) more than virtual (18.2%). Of a total of 73 scheduled visits, 8 (11%) were no-showed. Patients who self-referred had the lowest no-show rate (5.6%) compared to those referred by a provider (12.8%) or nurse (12.5%). Of the patients included, 87.9% set a goal quit date. Average time until first and second follow-up was 34.6 and 130.4 days after goal quit date. Follow-up was defined as the date of the patient’s first message reply to the TTS-NP, or first visit following the goal quit date. A total of 51.9% (n = 14) and 63% (n = 17) reported cessation at the first and second follow-up. TTS-NP visit’s cost, independent of any other coverage, was less than other specialty visits in primary care. Conclusion. TTS-NP visits in primary care enabled patients to benefit from lower cost and longitudinal follow-up within a familiar setting. Over half of patients achieved cessation. Results of this program evaluation suggest support for TTS-certified providers in primary care.

Scholars have found that citizens tend to evaluate European institutions in light of how they feel about their own domestic institutions (second-order evaluations). We argue that this approach is more appropriate for understanding international courts than is the legitimacy approach of the law and courts literature. While studies applying the second-order evaluations approach have overwhelmingly focused on EU institutions, here we seek to determine whether second-order evaluations are also characteristic of citizens’ opinions about the European Court of Human Rights. We evaluate our hypotheses using a sample of the British population and find strong support for the general second-order evaluation.

Research conducted in the context of a disaster or public health emergency is essential to improve knowledge about its short- and long-term health consequences, as well as the implementation and effectiveness of response and recovery strategies. Integrated approaches to conducting Disaster Research Response (DR2) can answer scientific questions, while also providing attendant value for operational response and recovery. Here, we propose a Concept of Operations (CONOPS) template to guide the collaborative development and implementation of DR2 among academic public health and public health agencies, informed by previous literature, semi-structured interviews with disaster researchers from academic public health across the United States, and discussion groups with public health practitioners. The proposed CONOPS outlines actionable strategies to address DR2 issues before, during, and after disasters for public health scholars and practitioners who seek to operationalize or enhance their DR2 programs. Additional financial and human resources will be necessary to promote widespread implementation of collaborative DR2 programs.

Disasters have many deleterious effects and are becoming more frequent. From a health-care perspective, disasters may cause periods of stress for hospitals and health-care systems. Telemedicine is a rapidly growing technology that has been used to improve access to health-care during disasters. Telemedicine applied in disasters is referred to as disaster telemedicine. Our objective was to conduct a scoping literature review on current use of disaster telemedicine to develop recommendations addressing the most common barriers to implementation of a telemedicine system for regional disaster health response in the United States. Publications on telemedicine in disasters were collected from online databases. This included both publications in English and those translated into English. Predesigned inclusion/exclusion criteria and a PRISMA flow diagram were applied. The PRISMA flow diagram was used on the basis that it would help streamline the available literature. Literature that met the criteria was scored by 2 reviewers who rated relevance to commonly identified disaster telemedicine implementation barriers, as well as how disaster telemedicine systems were implemented. We also identified other frequently mentioned themes and briefly summarized recommendations for those topics. Literature scoring resulted in the following topics: telemedicine usage (42 publications), system design and operating models (43 publications), as well as difficulties with credentialing (5 publications), licensure (6 publications), liability (4 publications), reimbursement (5 publications), and technology (24 publications). Recommendations from each category were qualitatively summarized.

Understanding place-based contributors to health requires geographically and culturally diverse study populations, but sharing location data is a significant challenge to multisite studies. Here, we describe a standardized and reproducible method to perform geospatial analyses for multisite studies. Using census tract-level information, we created software for geocoding and geospatial data linkage that was distributed to a consortium of birth cohorts located throughout the USA. Individual sites performed geospatial linkages and returned tract-level information for 8810 children to a central site for analyses. Our generalizable approach demonstrates the feasibility of geospatial analyses across study sites to promote collaborative translational research.

Distinguished Oral

Background: Shared Healthcare Intervention to Eliminate Life-threatening Dissemination of MDROs in Orange County, California (SHIELD OC) was a CDC-funded regional decolonization intervention from April 2017 through July 2019 involving 38 hospitals, nursing homes (NHs), and long-term acute-care hospitals (LTACHs) to reduce MDROs. Decolonization in NH and LTACHs consisted of universal antiseptic bathing with chlorhexidine (CHG) for routine bathing and showering plus nasal iodophor decolonization (Monday through Friday, twice daily every other week). Hospitals used universal CHG in ICUs and provided daily CHG and nasal iodophor to patients in contact precautions. We sought to evaluate whether decolonization reduced hospitalization and associated healthcare costs due to infections among residents of NHs participating in SHIELD compared to nonparticipating NHs. Methods: Medicaid insurer data covering NH residents in Orange County were used to calculate hospitalization rates due to a primary diagnosis of infection (counts per member quarter), hospital bed days/member-quarter, and expenditures/member quarter from the fourth quarter of 2015 to the second quarter of 2019. We used a time-series design and a segmented regression analysis to evaluate changes attributable to the SHIELD OC intervention among participating and nonparticipating NHs. Results: Across the SHIELD OC intervention period, intervention NHs experienced a 44% decrease in hospitalization rates, a 43% decrease in hospital bed days, and a 53% decrease in Medicaid expenditures when comparing the last quarter of the intervention to the baseline period (Fig. 1). These data translated to a significant downward slope, with a reduction of 4% per quarter in hospital admissions due to infection (P < .001), a reduction of 7% per quarter in hospitalization days due to infection (P < .001), and a reduction of 9% per quarter in Medicaid expenditures (P = .019) per NH resident. Conclusions: The universal CHG bathing and nasal decolonization intervention adopted by NHs in the SHIELD OC collaborative resulted in large, meaningful reductions in hospitalization events, hospitalization days, and healthcare expenditures among Medicaid-insured NH residents. The findings led CalOptima, the Medicaid provider in Orange County, California, to launch an NH incentive program that provides dedicated training and covers the cost of CHG and nasal iodophor for OC NHs that enroll.

Funding: None

Disclosures: Gabrielle M. Gussin, University of California, Irvine, Stryker (Sage Products): Conducting studies in which contributed antiseptic product is provided to participating hospitals and nursing homes. Clorox: Conducting studies in which contributed antiseptic product is provided to participating hospitals and nursing homes. Medline: Conducting studies in which contributed antiseptic product is provided to participating hospitals and nursing homes. Xttrium: Conducting studies in which contributed antiseptic product is provided to participating hospitals and nursing homes.

The coronavirus disease 2019 (COVID-19) has greatly impacted health-care systems worldwide, leading to an unprecedented rise in demand for health-care resources. In anticipation of an acute strain on established medical facilities in Dallas, Texas, federal officials worked in conjunction with local medical personnel to convert a convention center into a Federal Medical Station capable of caring for patients affected by COVID-19. A 200,000 square foot event space was designated as a direct patient care area, with surrounding spaces repurposed to house ancillary services. Given the highly transmissible nature of the novel coronavirus, the donning and doffing of personal protective equipment (PPE) was of particular importance for personnel staffing the facility. Furthermore, nationwide shortages in the availability of PPE necessitated the reuse of certain protective materials. This article seeks to delineate the procedures implemented regarding PPE in the setting of a COVID-19 disaster response shelter, including workspace flow, donning and doffing procedures, PPE conservation, and exposure event protocols.