Clinical And Translational Science Research Articles

Pharmacists as accessible health care providers: quantifying the opportunity.

BACKGROUND: Community pharmacists are well positioned to improve patient access to care, which may assist value-based care programs in reaching patients. While pharmacy accessibility is broadly acknowledged, much of the research supporting accessibility claims is poor quality. OBJECTIVE: To quantify the accessibility of pharmacists in comparison with physicians or qualified health care professionals (QHP) in a commercially insured population. METHODS: IBM MarketScan claims data from 2018 were used for this cross-sectional study. Beneficiaries included in the primary analysis were aged 18-64 years, enrolled with pharmacy benefits in 2018 for 12 months, and had at least 1 valid prescription drug claim or evaluation and management (E&M) code in 2018. Unique pharmacy visits were defined using a 6-day fill window for prescription fill dates, while visits to physicians or other QHP were defined as unique service dates tied to an E&M code. We assessed differences in visit frequency for the full sample, those with multiple chronic conditions (MCC), and "superutilizers" (top 5% based on total cost of care). Our statistical approach included descriptive statistics and the Wilcoxon sign rank test. RESULTS: After applying the inclusion criteria, 11,720,958 beneficiaries were included in the full sample. The MCC cohort contained 13.8% of the total sample (mean [SD] age: 50.8 [10.8]; 908,880 [56.1%] female). Finally, the superutilizers were 57.3% female with an average age of 48.4 years and comprised 5.3% of the total sample. The median number of pharmacy and physician or QHP visits for the full sample were 5 and 3 (P < 0.0001), yielding a pharmacy to physician or QHP visit ratio of 1.7:1. The MCC cohort had a median of 13 pharmacy visits and 7 physician or QHP visits (ratio 1.9:1; P < 0.0001), and the superutilizers had a median of 14 pharmacy visits and 9 physician or QHP visits (ratio 1.6:1; P < 0.0001). CONCLUSIONS: This study found that patients visit their community pharmacies almost twice as often as they visit their physicians or other QHP. Study findings emphasize the accessibility of community pharmacists and highlight the role of community pharmacists in improving patient engagement in all care programs, including value-based care programs. DISCLOSURES: The database infrastructure used for this project was funded by the Department of Epidemiology, University of North Carolina (UNC) Gillings School of Global Public Health; the Cecil G. Sheps Center for Health Services Research, UNC; the CER Strategic Initiative of UNC's Clinical Translational Science Award (UL1TR001111); and the UNC School of Medicine. All authors are employed by the UNC School of Pharmacy. Urick declares consulting fees from Cardinal Health. The other authors have no conflicts of interest to disclose. Portions of this work were previously presented at the AMCP 2021 Virtual, April 12-16, 2021.

Role of the non-invasive imaging techniques in monitoring and understanding the evolution of brain edema.

Human brain injury elicits accumulation of water within the brain due to a variety of pathophysiological processes. As our understanding of edema emerged two temporally (and cellular) distinct processes were identified, cytotoxic and vasogenic edema. The emergence of both types of edema is reflected by the temporal evolution and is influenced by the underlying pathology (type and extent). However, this two-edema compartment model does not adequately describe the transition between cytotoxic and vasogenic edema. Hence, a third category has been proposed, termed ionic edema, that is observed in the transition between cytotoxic and vasogenic edema. Magnetic resonance neuroimaging of edema today primarily utilizes T2-weighted (T2WI) and diffusion-weighted imaging (DWI). Clinical diagnostics and translational science studies have clearly demonstrated the temporal ability of both T2WI and DWI to monitor edema content and evolution. DWI measures water mobility within the brain reflecting cytotoxic edema. T2WI at later time points when vasogenic edema develops visualizes increased water content in the brain. Clinically relevant imaging modalities, including ultrasound and positron emission tomography, are not typically used to assess edema. In sum, edema imaging is an important cornerstone of clinical diagnostics and translational studies and can guide effective therapeutics manage edema and improve patient outcomes.

POS-233 COMPARISON OF GLOMERULAR FILTRATION RATE EQUATIONS IN A RURAL NEW MEXICO COHORT

Estimated glomerular filtration rate (eGFR) equations use plasma filtration markers to predict kidney function. There are scarce data regarding the performance of various eGFR equations in Indigenous and Hispanic populations. Serum creatinine (SCr) has been historically used to estimate eGFR, but Cystatin C (CysC) and beta-2 microglobulin (B2M) may have less inter-person variability based on muscle mass, age and gender. We hypothesized that the various SCr, CysC or B2M-based eGFR equations will evaluate kidney function differently among Hispanics and Native Americans residing in rural New Mexico (NM). We studied 210 participants from the Community-Based Study of the Epidemiology of Chronic Kidney Disease (CKD) in Cuba, NM and Surrounding Areas (COMPASS). At study enrollment clinical measurements, questionnaires and serum blood specimens were obtained. Samples were analyzed at University of New Mexico’s Clinical Translational Sciences Center and TriCore Reference Laboratories. The method comparison between three eGFR equations was tested using Bland-Altman plots. Participants were racially diverse (American Indian 31.43%), but predominantly white (39.05%), Hispanic (53.81%), women (61.43%) and overweight (BMI 30.29 ± 6.84) (see Table below). The mean difference between CysC-eGFR and SCr-eGFR was 25.4 ml/min/1.73m2, and that between CysC-eGFR and B2M-eGFR was 25.3 ml/min/1.73m2. Agreement between CysC-eGFR and B2M-eGFR was excellent, with a mean difference of -0.12 ml/min/1.73m2 (Figure). Tabled 1Characteristics of Study PopulationSummary (Number of Participants = 210)Age49.80 ± 17.86GenderMales81 (38.57 %)Females129 (61.43 %)EthnicityHispanic or Latino113 (53.81 %)Not Hispanic or Latino96 (45.71 %)Unknown/not reported1 (0.48 %)RaceAmerican Indian/Alaska Natives66 (31.43 %)More than one race6 (2.86 %)Unknown/Not reported56 (26.67 %)White82 (39.05 %)Highest Degree of EducationK-1245 (21.43 %)High School degree87 (41.43 %)Higher than High School degree77 (36.66 %)Not disclosed1 (0.48 %)Health Insurance TypeMedicare34 (16.19 %)Medicaid52 (24.76 %)Other51 (24.29 %)2+ type of insurance55 (26.19 %)Uninsured/not disclosed18 (8.57 %)Blood Pressure (BP)Mean ± stdSystolic BP127 ± 14Diastolic BP77 ± 11Laboratory Values (serum)Body Mass Index (BMI)30.29 ± 6.84Serum glucose levels (mg/dL)121.27 ± 58.84Hemoglobin A1C (%)6.2% ± 0.02Serum Creatinine (mg/dL)0.9 ± 0.25Cystatin C (mg/L)0.72 ± 0.35High Sensitivity C-Reactive Protein (mg/L)4.97 ± 6.47BUN (mg/dL)13.83 ± 4.92Albumin (mg/dL)4.20 ± 0.36Hemoglobin (gm/dL)15.01 ± 1.56Hematocrit (%)44.63 ± 3.96Phosphorous (mg/dL)3.4 ± 0.68Uric Acid (mg/dL)5.12 ± 1.33Calcium (mg/dL)9.51 ± 0.53 Open table in a new tab View Large Image Figure ViewerDownload Hi-res image Download (PPT) As the replacement of race-adjusted, SCr-eGFR with CysC-eGFR gains momentum, it is important to understand potential analytical biases introduced by CysC in other racial and ethnic groups. B2M-eGFR does not require adjustment for age, race, or gender thus may be a more optimal method to calculate GFR. Further studies with objective measurements of kidney function are needed to validate these findings.

45022 Exploring Career Development Needs of Junior Investigators in Clinical Translational Science

ABSTRACT IMPACT: By understanding Junior investigator characteristics and CTSA support services which strongly influence scientific productivity and impact, we will inform and improve research training and enhance the career development of future generations of clinical and translational science researchers. OBJECTIVES/GOALS: In the field of clinical and translational science, the career trajectory and definition of Junior Investigators (JIs) vary greatly. This study aims to investigate JI characteristics, training, and support that contribute to career development at the University of California Los Angeles (UCLA) Clinical and Translation Science Institute (CTSI). METHODS/STUDY POPULATION: Every 18 months, the UCLA CTSI administers the Longitudinal Scientific Achievement Survey, which collects information on the predictors of scientific productivity and impact. In 2018, a special supplement was added to survey JIs who received CTSA support between 2011 and 2017 (n=305), including questions on knowledge, use, and effectiveness of CTSA specific support, barriers and facilitators of research, scientific productivity, and perceived scientific impact. A literary analysis was conducted to explore previous categorizations of JIs. The JIs in our sample conducted bench to bedside, population and policy research at our four partner sites. Bivariate and logistic regression analysis were conducted to examine the significant predictors of a new grant award attributed to the CTSA support/services. RESULTS/ANTICIPATED RESULTS: The survey response rate was 82% (n=250). Respondents include core voucher co-investigators, enrollees in the Training Program in Translational Science, and K- and K-to-R workshop participants. Bivariate results showed new grant awardees significantly more likely to have the following characteristics: physician scientist with an MD and PhD (47%), pilot grant awardee (42%), core voucher awardee (49%), four or more types of CTSI support (48%), prior affiliation with an NIH institute/center other than NCATS (42%), and reported at least one impact in science, health, and/or the community (72%). Multivariate results showed that investigators with a prior core voucher award, a prior NIH affiliation, or reported one or more impacts were the strongest predictors of obtaining a new grant (each with OR&gt;=4.0). DISCUSSION/SIGNIFICANCE OF FINDINGS: The most successful investigators consulted with NIH program officers and received feedback on their research plans and methods. Sufficient funding is crucially important to research progression. In our CTSA hub, vouchers and grants to initiate new studies or offset costs of existing research are consistent predictors of new extramural funding.

50565 CTSA collaboration to support K-12 school re-opening in the COVID-19 pandemic

ABSTRACT IMPACT: The mobilization of a CTSA-sponsored team with multi-disciplinary translational science expertise enabled the university to provide a range of T1-T4 expertise to a large, complex school district that resulted in permanent learning and data science infrastructure. OBJECTIVES/GOALS: The Clinical Translational Science Institute (CTSI) formed a multidisciplinary science team to provide expertise in support of the re-opening of in-person learning in the second-largest U.S. school district during the COVID-19 pandemic. METHODS/STUDY POPULATION: The assembled interdisciplinary science team provided expertise in epidemiology, machine learning, causal inference and agent-based modeling, data and improvement science, biostatistics, clinical and laboratory medicine, health education, community engagement, and experience in outbreak investigation and management. The team included TL1 pre and postdoctoral fellows and mobilized scientists from multiple professional schools and T1-T4 stages of translational research. RESULTS/ANTICIPATED RESULTS: Tangible outcomes achieved using this team approach included the development of practical metrics for use in the school community, a learning process, the integration of preventive design elements into a testing and tracing program, and targeted and data-driven health education. The team, for example, generated new data displays for community engagement and collaborated with the school district in their use to visualize, learn from, and act on variation across a 700 square mile region. DISCUSSION/SIGNIFICANCE OF FINDINGS: Novel translational methods can be used to establish a learning environment and data science infrastructure that complements efforts of public health agencies to aid schools in the COVID-19 pandemic. These new capabilities apply to COVID-19 testing and vaccines and can be mobilized for future population health challenges faced by school districts.

Abstract OT-22-01: Opportunities and lessons learned in using electronic health record patient portal (MyChart) for recruitment to the population-based WISDOM study

Abstract Background: WISDOM is a preference-tolerant, pragmatic study comparing annual mammogram screening to personalized, risk-based breast screening in healthy women with a target accrual of 100,000. This sizable recruitment goal requires creative and broad-based strategies that are not typical for traditional clinical research. One of the recruitment methods is use of an electronic health record patient portal (Epic’s MyChart) to invite patients to participate in research. We tested various MyChart implementation strategies across WISDOM recruitment sites and report response rates, barriers and lessons learned. The study is registered on ClinicalTrials.gov, NCT02620852. Methods: Women aged 40-74 years with no history of breast cancer, DCIS, or double mastectomy can join the WISDOM Study online at wisdomstudy.org. Participants either elect to be randomized or self-select one of the study arms, the control (annual mammogram screening) arm or the treatment (personalized, risk-based breast screening) arm. All study steps can be completed electronically, with no requirement to travel to a study site. University of California, Los Angeles (UCLA) was the first WISDOM site to gain approval to use MyChart as a recruitment tool as part of the Clinical Translational Science Institute pilot in Spring 2018. The pilot was designed to demonstrate feasibility, patient response, and recruitment metrics. Following UCLA’s pilot, additional WISDOM sites received approval to use MyChart; however, implementation differed across sites based on local medical center leadership decisions. MyChart Implementation: As of July 2020, use of MyChart is ongoing at five of WISDOM’s six initial recruitment sites (UCLA, Sanford Health, UCSF, UCSD, UCI). Three sites (UCLA, Stanford, and UCSF) implemented MyChart broadly, and two sites (UCI and UCSD) are phasing in MyChart recruitment. UCLA and Sanford Health implemented MyChart recruitment through a centralized approach targeting all eligible patients and sending a MyChart invitation with a link to the study’s enrollment website. UCSF was approved to send WISDOM information on the MyChart portal, but the patients must opt in to learn more by outreach from a research coordinator. UCSD and UCI approaches are more limited requiring departmental or primary care provider approval for communications to be sent to patients. Results: MyChart enabled direct communication to a large number of potential study participants at UCLA and Sanford Health (UCLA 107,829, Sanford Health 86,684) during a 12-month period. The experiences of both sites were similar in that 50% of individuals read the MyChart message, 2.5-5% registered for additional information, and 1.5-2.5% consented to participate. UCSF’s implementation approach was similar with 8005 individuals invited, 6.6% indicating interest to participate, and 2.4% consenting. Although the number of consented participants represented a small portion of the total women consented to join the study to date, the recruitment rates from using MyChart were 2.5-10X higher compared to sites that did not use it or were in pilot phase. Participating sites saw 30%-50% increased recruitment rates during periods when MyChart messages were in use. Implementations at the departmental (UCSD) and primary care provider level (UCI) demonstrated similar trends (3.8% and 3% consented respectively), albeit with smaller samples. Conclusions: Use of electronic health record patient portal (MyChart) recruitment for the WISDOM Study increased enrollment rate by site and is a cost-effective approach to recruiting for large scale trials with broad eligibility criteria like the WISDOM Study. Citation Format: Antonio Petruse, Alyssa Rocha, Liliana Johansen, Neil Wenger, Mandy Che, Steele Fors, Hannah L Park, Janet Wernisch, Irene Acerbi, Allison S Fiscalini, Jasmin Hassam, Andrea LaCroix, Barbara Parker, Lisa Madlensky, Laura Van't Veer, Celia Kaplan, Hoda Anton-Culver, Andrea Kaster, Skye Stewart, Samrrah Rouf, Alexander Borowsky, Ian Hurley, Robert Hiatt, Vivian Lee, Diane Heditsian, Susie Brain, Olufunmilayo Olopade, Deepa Sheth, Laura Esserman, Wisdom Study and Athena Breast Health Network Investigators and Advocate Partners, Arash Naeim. Opportunities and lessons learned in using electronic health record patient portal (MyChart) for recruitment to the population-based WISDOM study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-22-01.

Circulating mitochondrial DNA is an early indicator of severe illness and mortality from COVID-19.

BackgroundMitochondrial DNA (MT-DNA) are intrinsically inflammatory nucleic acids released by damaged solid organs. Whether circulating cell-free MT-DNA quantitation could be used to predict the risk of poor COVID-19 outcomes remains undetermined.MethodsWe measured circulating MT-DNA levels in prospectively collected, cell-free plasma samples from 97 subjects with COVID-19 at hospital presentation. Our primary outcome was mortality. Intensive care unit (ICU) admission, intubation, vasopressor, and renal replacement therapy requirements were secondary outcomes. Multivariate regression analysis determined whether MT-DNA levels were independent of other reported COVID-19 risk factors. Receiver operating characteristic and area under the curve assessments were used to compare MT-DNA levels with established and emerging inflammatory markers of COVID-19.ResultsCirculating MT-DNA levels were highly elevated in patients who eventually died or required ICU admission, intubation, vasopressor use, or renal replacement therapy. Multivariate regression revealed that high circulating MT-DNA was an independent risk factor for these outcomes after adjusting for age, sex, and comorbidities. We also found that circulating MT-DNA levels had a similar or superior area under the curve when compared against clinically established measures of inflammation and emerging markers currently of interest as investigational targets for COVID-19 therapy.ConclusionThese results show that high circulating MT-DNA levels are a potential early indicator for poor COVID-19 outcomes.FundingWashington University Institute of Clinical Translational Sciences COVID-19 Research Program and Washington University Institute of Clinical Translational Sciences (ICTS) NIH grant UL1TR002345.

CTS teams: a new model for translational team training and team science intervention.

Clinical/translational science (CTS) is team-based, requiring effective collaboration and communication across many disciplines involving a variety of stakeholders. We implemented a pre-doctoral team-based training model with didactic and experiential curricular interventions to support the development of CTS research skills in a cross-disciplinary team environment. We assessed the potential impact of this new training model as a team science intervention that can catalyze new cross-disciplinary collaborations across the institution. Between 2016 and 2020, 32 pre-doctoral students and 26 co-mentors participated in the assessment of the CTS Team program over a two-year period of TL1 training grant support. Data collection and analyses followed a program logic model and used a variety of metrics for clinical and translational scientist career success. CTS training in the context of CTS Teams supported improved self-efficacy for clinical research skills and resulted in a significant increase in the frequency of participation in cross-disciplinary collaborative activities by both trainees and mentors. Most CTS Team co-mentor pairs had not previously collaborated. Two-thirds of the co-mentors plan to continue collaborating, and most (85%) currently use or plan to use collaboration tools, for example, written collaboration plans, authorship agreements. The CTS Team training model provides a unique clinical and translational science team training experience that embeds authentic cross-disciplinary research collaboration into PhD research projects. It establishes trainee cohorts that are diverse in terms of scientific disciplines and translational research phases, and creates a new cross-disciplinary community of practice across faculty members and research groups in multiple colleges.

The Disparities Researchers Equalizing Access for Minorities (DREAM) Scholars program: career development for underrepresented health equity researchers.

Diversity remains low among US colleges faculty, with only 3% identifying as Black or Hispanic. Moreover, underrepresented racial minority faculty often face unique challenges and are less likely than their white counterparts to earn higher academic rank, tenure, and funding, especially those who study health equity. We developed a novel program for health-equity focused pre-docs and junior faculty. The Disparities Researchers Equalizing Access for Minorities (DREAM) Scholars is a 24-month career development program led by the Center for Clinical and Translational Science (CCTS) that provides pilot and travel funding, career development seminars, mentoring, and writing retreats. We report the outcomes of the first Scholar cohort (N = 10), pre-docs n = 6; assistant professors, n = 4; seven were Black, one Hispanic, two White, one who identified as non-binary. At the end of the program, Scholars coauthored 34 manuscripts, 9 abstracts and 8 grants. Semi-structured interviews revealed seven major program strengths: funding, support and sense of community, accountability, exposure to translational science, network expansion, and exposure to multidisciplinary peers. Scholars provided feedback useful for subsequent cohorts. The DREAM program provided accountability and fostered a sense of community, expanded professional networks and enhanced scholarly productivity. The program serves as a model for implementation throughout the CCTSs.

Educating for diversity, equity, and inclusion: A review of commonly used educational approaches.

Diversity, equity, and inclusion (DEI) are fundamentally important concepts for advancing clinical and translational science (CTS) education. CTS education spans a wide range of disciplines from cell biology to clinical and community/population research. This large scope both in terms of intellectual areas and target groups requires an understanding of existing educational approaches for DEI as we translate DEI from mere concepts into equitable actions within CTS education. In this review, we provide the readers with the most common DEI educational approaches, including cultural humility, bias training, and improving mentoring to diversify the workforce. DEI educational materials can achieve maximal success and long-term impact when implemented as institutional-wide interventions, and the materials are not seen as an isolated or independent curriculum. Approaches, strategies, and programs to achieve this are many. However, many questions remain unanswered about what the best approach, strategies, and programs are to be implemented in institutional-wide education that will be embedded in CTS education.

Feasibility of a virtual Facebook community platform for engagement on health research.

Community engagement is important for advancing Clinical and Translational Science (CTS), but face-to-face engagement has limited reach and scale. We examined the feasibility of a novel virtual Facebook community platform for public engagement on health research statewide in Minnesota. The Facebook platform, MN Research Link, was evaluated from June 19, 2019 to June 30, 2020. Facebook advertisements and boosts were used to recruit followers. Content, based on prior formative work, included health research information and interactive postings (e.g., live interviews with researchers). Standard metrics obtained from Facebook analytics included participation (followers), content reach (views), and engagement (likes, shares, comments, clicks). During the 12-month period, we acquired 1406 followers (31% rural residents), with a retention of followers of 99.7%. Mean number of views per month was 9379.83 (Mdn = 2791, range 724-41,510). Engagement metrics indicated a mean of 535.2 likes, shares, comments, and/or clicks per month (Mdn = 296.5, range 55-1535). The page continued to acquire new followers, but a slight decrease in engagement was observed in the final months after state COVID-19 mitigation strategies were implemented. As the complexity of CTS continues to grow, along with social distancing measures resulting from the COVID-19 pandemic, the availability of virtual digital platforms to reach and engage community stakeholders in conversations about health and research has increasing importance. Preliminary findings from this program evaluation indicate that a Facebook community platform is feasible to engage Minnesota residents in conversations around health and research topics. Future work will evaluate its potential for reach, scale, and sustainability.

Practicing With Uncertainty: Kidney Transplantation During the COVID-19 Pandemic

The coronavirus disease 2019 (COVID-19) pandemic required transplant nephrologists, surgeons, and care teams to make decisions about the full spectrum of transplant program operations and clinical practices in the absence of experience or data. Initially, across the country, there was a reduction in kidney transplant procedures and a striking pause in the conduct of living donation and living-donor transplant surgeries. Aspects of candidate evaluation and follow-up rapidly converted to telehealth. Months into the pandemic, much has been learned from experiences worldwide, yet many questions remain. In this Perspective, we reflect on some of the practice decisions made by the transplant community in the initial response to the pandemic and consider lessons learned, including those related to the risks, benefits, and logistical considerations of proceeding with versus delaying deceased-donor transplantation, living donation, and living-donor transplantation during the pandemic. We review the evolution of therapeutic strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their use in transplant recipients, current consensus related to immunosuppression management in infected transplant recipients, and emerging information on vaccination against SARS-CoV-2. We share our thoughts on research priorities, discuss the areas in which we are still practicing with uncertainty, and look ahead to the next phase of the pandemic response.

Re-engineering The Clinical Research Enterprise in Response to COVID-19: The Clinical Translational Science Award (CTSA) experience and proposed playbook for future pandemics.

The 2020 COVID-19 pandemic has had a profound impact on the clinical research enterprises at the 60 Clinical and Translational Science Award (CTSA) Hubs throughout the nation. There was simultaneously a need to expand research to obtain crucial data about disease prognosis and therapy and enormous limitations on conducting research as localities and institutions limited travel and person-to-person contact. These imperatives resulted in major changes in the way research was conducted, including expediting Institutional Review Board review, shifting to remote interactions with participants, centralizing decision-making in prioritizing research protocols, establishing biobanks, adopting novel informatics platforms, and distributing study drugs in unconventional ways. National CTSA Steering Committee meetings provided an opportunity to share best practices and develop the idea of capturing the CTSA program experiences in a series of papers. Here we bring together the recommendations from those papers in a list of specific actions that research sites can take to strengthen operations and prepare for similar future public health emergencies. Most importantly, creative innovations developed in response to the COVID-19 pandemic deserve serious consideration for adoption as new standards, thus converting the painful trauma of the pandemic into "post-traumatic growth" that makes the clinical research enterprise stronger, more resilient, and more effective.

Re-engineering The Clinical Research Enterprise in Response to COVID-19: The Clinical Translational Science Award (CTSA) experience and proposed playbook for future pandemics

Re-engineering The Clinical Research Enterprise in Response to COVID-19: The Clinical Translational Science Award (CTSA) experience and proposed playbook for future pandemics

Discoidin domain receptor 1 activation links extracellular matrix to podocyte lipotoxicity in Alport syndrome.

BackgroundDiscoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that is activated by collagens that is involved in the pathogenesis of fibrotic disorders. Interestingly, de novo production of the collagen type I (Col I) has been observed in Col4a3 knockout mice, a mouse model of Alport Syndrome (AS mice). Deletion of the DDR1 in AS mice was shown to improve survival and renal function. However, the mechanisms driving DDR1-dependent fibrosis remain largely unknown.MethodsPodocyte pDDR1 levels, Collagen and cluster of differentiation 36 (CD36) expression was analyzed by Real-time PCR and Western blot. Lipid droplet accumulation and content was determined using Bodipy staining and enzymatic analysis. CD36 and DDR1 interaction was determined by co-immunoprecipitation. Creatinine, BUN, albuminuria, lipid content, and histological and morphological assessment of kidneys harvested from AS mice treated with Ezetimibe and/or Ramipril or vehicle was performed.FindingsWe demonstrate that Col I-mediated DDR1 activation induces CD36-mediated podocyte lipotoxic injury. We show that Ezetimibe interferes with the CD36/DDR1 interaction in vitro and prevents lipotoxicity in AS mice thus preserving renal function similarly to ramipril.InterpretationOur study suggests that Col I/DDR1-mediated lipotoxicity contributes to renal failure in AS and that targeting this pathway may represent a new therapeutic strategy for patients with AS and with chronic kidney diseases (CKD) associated with Col4 mutations.FundingThis study is supported by the NIH grants R01DK117599, R01DK104753, R01CA227493, U54DK083912, UM1DK100846, U01DK116101, UL1TR000460 (Miami Clinical Translational Science Institute, National Center for Advancing Translational Sciences and the National Institute on Minority Health and Health Disparities), F32DK115109, Hoffmann-La Roche and Alport Syndrome Foundation.

Tales from New York City, the pandemic epicenter: A case study of COVID-19 impact on clinical and translational research training at the Icahn School of Medicine at Mount Sinai.

In the spring of 2020, New York City was at the epicenter of the COVID-19 pandemic in the USA, resulting in disruption of TL1 and KL2-mentored Clinical and Translational Science (CTS) research at the Icahn School of Medicine at Mount Sinai (ISMMS). The impact of the pandemic on trainees' research productivity and career plans was explored using a qualitative survey. Participant responses were analyzed using coding and categorization. Six key themes emerged: redirection of effort, reduced access to people, lack of access to resources, home as a workplace, future uncertainty, and stress and anxiety. Insight into participant experiences allows for the development of support strategies and resources to address trainee needs.

Patients With MH Disorders Found More Susceptible to COVID-19, Death

Patients With MH Disorders Found More Susceptible to COVID-19, Death

In celebration of American Pharmacists Month, a look at lives dedicated to pharmacy

In celebration of American Pharmacists Month, a look at lives dedicated to pharmacy

Research ethics challenges during the COVID-19 pandemic: what should and what should not be done

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Carle Illinois College of Medicine.

Carle Illinois College of Medicine.