Browsing by Author "Moe, Sharon"
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Item 18F-NaF and 18F-FDG as molecular probes in the evaluation of atherosclerosis(Springer Nature, 2018-11) McKenney-Drake, Mikaela L.; Moghbel, Mateen C.; Paydary, Koosha; Alloosh, Mouhamad; Houshmand, Sina; Moe, Sharon; Salavati, Ali; Sturek, Jeffrey M.; Territo, Paul R.; Weaver, Connie; Werner, Thomas J.; Høilund-Carlsen, Poul Flemming; Sturek, Michael; Alavi, Abass; Cellular and Integrative Physiology, School of MedicineThe early detection of atherosclerotic disease is vital to the effective prevention and management of life-threatening cardiovascular events such as myocardial infarctions and cerebrovascular accidents. Given the potential for positron emission tomography (PET) to visualize atherosclerosis earlier in the disease process than anatomic imaging modalities such as computed tomography (CT), this application of PET imaging has been the focus of intense scientific inquiry. Although 18F-FDG has historically been the most widely studied PET radiotracer in this domain, there is a growing body of evidence that 18F-NaF holds significant diagnostic and prognostic value as well. In this article, we review the existing literature on the application of 18F-FDG and 18F-NaF as PET probes in atherosclerosis and present the findings of original animal and human studies that have examined how well 18F-NaF uptake correlates with vascular calcification and cardiovascular risk.Item 192. Health Equity Starts with Us: Recommendations from the Indiana Clinical and Translational Sciences Institute Racial Justice and Health Equity Task Force(Cambridge University Press, 2022) Sotto-Santiago, Sylk; Tucker Edmonds, Brownsyne; Wiehe, Sarah; Moe, SharonOBJECTIVES/GOALS: The Indiana CTSI Strategy Committee charged the Racial Justice and Health Equity Taskforce to identify priorities with short-term and long-term goals consistent with the I-CTSI mission. In addition, I-CTSI leadership asked for a general description of current state and the resources necessary to achieve the proposed goals. METHODS/STUDY POPULATION: The Taskforce applied an inclusive excellence model to the way we look at the I-CTSI structure, policies, and programs while performing an environmental scan within and across I-CTSI partner institutions. In order to reach equitable solutions and consensus, listening tours were held with partner stakeholders guided by the SOAR framework for strategic planning. This approach allowed us to assess current resources, needs, and gaps across the system, along with a baseline of measures currently monitored. Taskforce members openly discussed strengths and opportunities for enhancement of current programs and services. In addition, these conversations offered an opportunity to disrupt existing practices and through collective agency we identified priority areas that promote equity, diversity and inclusion. RESULTS/ANTICIPATED RESULTS: The Taskforce identified recurring themes in conversations with all partners, which led to the formation of three working groups that examined recruitment broadly: workforce, staffing, and research participation; professional development across all stakeholders from community members to I-CTSI staff; and data-centered metrics informing current state, decision-making, and accountability. Recommendations included these priorities, content, and implementation strategies. The Taskforce delivered a report to the I-CTSI leadership fostering the promotion of diversity, equity and inclusion along with a systematic collection of gender, race, and ethnicity data for individuals utilizing I-CTSI services and resources requiring additional metrics and tracking. DISCUSSION/SIGNIFICANCE: The pandemic shed light on the manner in which marginalized groups are rendered particularly vulnerable to death and disease by systemic and structural racism. The I-CTSI recognized that we cannot advance population health without attending to root causes of inequity and that includes our internal structure. We offer a potential model for other CTSAs.Item 4438 Twenty-four-hour Urinary Sodium Excretion Estimated from a Spot Urine Sample May Be Used as an Indicator of Intake in CKD Patients(Cambridge University Press, 2020-07-29) Lobene, Andrea; Stremke, Elizabeth; Moorthi, Ranjani; Moe, Sharon; Hill Gallant, Kathleen M.; Medicine, School of MedicineOBJECTIVES/GOALS: Sodium (Na) intake can elevate blood pressure and is a factor in developing chronic kidney disease (CKD). Twenty-four-hour urinary Na (24hUNa) is the gold standard for assessing Na intake but is burdensome. Validated equations estimate 24hUNa (e24hUNa) from a spot urine sample, but these estimations are not validated against a known Na intake in CKD. METHODS/STUDY POPULATION: The current study is a secondary analysis of a 9-day controlled feeding study in moderate CKD patients matched to healthy adults. Only CKD patients were used for the current analyses (n = 8). Participants consumed a controlled diet for 9 days, providing ~2400 mg Na/d as determined by inductively coupled plasma optical emission spectroscopy (ICP). On days 7 and 8, participants collected all urine in an inpatient setting, beginning with a fasting sample on day 7. Urine sample mineral analyses were performed by ICP and urinary creatinine by the Jaffe reaction. The day 7 fasting urine sample was used to calculate e24hUNa using 6 published equations. Log-transformed Na intake, measured 24hUNa, and e24hUNa were compared by repeated-measures ANOVA with planned contrasts using SAS. RESULTS/ANTICIPATED RESULTS: Fifty percent of the CKD patients (n = 4) were female; 63% (n = 5) were white, and 37% (n = 3) were black. On average, participants were aged 56.6 ± 13.8 y with a BMI of 31.7 ± 9.4 kg/m2 and eGFR of 40.7 ± 7.9 mL/min. Based on actual food intake, average Na intake on day 7 was 2024 ± 388 mg. Average measured 24hUNa was 2529 ± 1334 mg. The main ANOVA was significant (p = 0.02). Results from the planned contrasts found that e24hUNa from the SALTED cohort, an equation developed specifically for CKD patients, was significantly higher than both Na intake (p<0.001) and measured 24hUNa (p = 0.007). For the remaining 5 equations, e24hUNa was not significantly different from measured 24hUNa nor dietary Na intake. DISCUSSION/SIGNIFICANCE OF IMPACT : Our results suggest that e24hUNa calculated using most published equations may provide a reliable and low-burden method of assessing dietary Na intake in moderate CKD patients. These findings should be confirmed in larger samples. Additional studies are needed to validate or dispute the use of the SALTED equation for estimating Na intake.Item Characteristics associated with access to kidney transplantation services in the Ohio River Valley(2024-04-26) Kelty, Catherine; Buford, Jade; Drewry, Kelsey; Adebiyi, Oluwafisayo; Sharfuddin, Asif; Fridell, Jonathan; Sher, Jawad; Huml, Anne; Moe, Sharon; Patzer, RachelItem Coronary Smooth Muscle Cell Cytodifferentiation and Intracellular Ca2+ Handling in Coronary Artery Disease(2019-08) Badin, Jill Kimberly; Sturek, Michael S.; Evans-Molina, Carmella; Moe, Sharon; Tune, Jonathan D.Metabolic syndrome (MetS) affects 1/3 of all Americans and is the clustering of three or more of the following cardiometabolic risk factors: obesity, hypertension, dyslipidemia, glucose intolerance, and insulin resistance. MetS drastically increases the incidence of coronary artery disease (CAD), which is the leading cause of mortality globally. A cornerstone of CAD is arterial remodeling associated with coronary smooth muscle (CSM) cytodifferentiation from a contractile phenotype to proliferative and osteogenic phenotypes. This cytodifferentiation is tightly coupled to changes in intracellular Ca2+ handling that regulate several key cellular functions, including contraction, transcription, proliferation, and migration. Our group has recently elucidated the time course of Ca2+ dysregulation during MetS-induced CAD development. Ca2+ transport mechanisms, including voltage-gated calcium channels, sarcoplasmic reticulum (SR) Ca2+ store, and sarco-endoplasmic reticulum Ca2+ ATPase (SERCA), are enhanced in early, mild disease and diminished in late, severe disease in the Ossabaw miniature swine. Using this well-characterized large animal model, I tested the hypothesis that this Ca2+ dysregulation pattern occurs in multiple etiologies of CAD, including diabetes and aging. The fluorescent intracellular Ca2+ ([Ca2+]i) indicator fura-2 was utilized to measure [Ca2+]i handling in CSM from lean and diseased swine. I found that [Ca2+]i handling is enhanced in mild disease with minimal CSM phenotypic switching and diminished in severe disease with greater phenotypic switching, regardless of CAD etiology. We are confident of the translatability of this research, as the Ca2+ influx, SR Ca2+ store, and SERCA functional changes in CSM of humans with CAD are similar to those found in Ossabaw swine with MetS. Single-cell RNA sequencing revealed that CSM cells from an organ culture model of CAD exhibited many different phenotypes, indicating that phenotypic modulation is not a discreet event, but a continuum. Transcriptomic analysis revealed differential expression of many genes that are involved in the osteogenic signaling pathway and in cellular inflammatory responses across phenotypes. These genes may be another regulatory mechanism common to the different CAD etiologies. This study is the first to show that CSM Ca2+ dysregulation is common among different CAD etiologies in a clinically relevant animal model.Item FGF23 and Cardiovascular Structure and Function in Advanced Chronic Kidney Disease(Wolters Kluwer, 2022-07-05) Halim, Arvin; Burney, Heather N.; Li, Xiaochun; Li, Yang; Tomkins, Claudia; Siedlecki, Andrew M.; Lu, Tzong-shi; Kalim, Sahir; Thadhani, Ravi; Moe, Sharon; Ting, Stephen M.S.; Zehnder, Daniel; Hiemstra, Thomas F.; Lim, Kenneth; Medicine, School of MedicineBackground: Fibroblast growth factor 23 (FGF23) is a bone-derived phosphatonin that is elevated in chronic kidney disease (CKD) and has been implicated in the development of cardiovascular disease. It is unknown whether elevated FGF23 in CKD is associated with impaired cardiovascular functional capacity, as assessed by maximum exercise oxygen consumption (VO2Max). We sought to determine whether FGF23 is associated with cardiovascular functional capacity in patients with advanced CKD and after improvement of VO2Max by kidney transplantation. Methods: We performed secondary analysis of 235 patients from the Cardiopulmonary Exercise Testing in Renal Failure and After Kidney Transplantation (CAPER) cohort, which recruited patients with stage 5 CKD who underwent kidney transplantation or were waitlisted and hypertensive controls. All patients underwent cardiopulmonary exercise testing (CPET) and echocardiography and were followed longitudinally for 1 year after study enrollment. Results: Patients across FGF23 quartiles differed in BMI (P=0.004) and mean arterial pressure (P<0.001) but did not significantly differ in sex (P=0.5) or age (P=0.08) compared with patients with lower levels of FGF23. Patients with higher FGF23 levels had impaired VO2Max (Q1: 24.2±4.8 ml/min per kilogram; Q4: 18.6±5.2 ml/min per kilogram; P<0.001), greater left ventricular mass index (LVMI; P<0.001), reduced HR at peak exercise (P<0.001), and maximal workload (P<0.001). Kidney transplantation conferred a significant decline in FGF23 at 2 months (P<0.001) before improvement in VO2Max at 1 year (P=0.008). Multivariable regression modeling revealed that changes in FGF23 was significantly associated with VO2Max in advanced CKD (P<0.001) and after improvement after kidney transplantation (P=0.006). FGF23 was associated with LVMI before kidney transplantation (P=0.003), however this association was lost after adjustment for dialysis status (P=0.4). FGF23 was not associated with LVMI after kidney transplantation in all models. Conclusions: FGF23 levels are associated with alterations in cardiovascular functional capacity in advanced CKD and after kidney transplantation. FGF23 is only associated with structural cardiac adaptations in advanced CKD but this was modified by dialysis status, and was not associated after kidney transplantation.Item Health Equity Starts with Us: Recommendations from the IN-CTSI Racial Justice and Health Equity Task Force(Association for Clinical and Translational Sciences, 2022-04-20) Sotto-Santiago, Sylk; Tucker Edmonds, Brownsyne; Wiehe, Sarah; Moe, SharonN/AItem How Good Are Provider Annotations?: A Machine Learning Approach(Wiley, 2017-01) Malas, M. Said; Kasthurirathne, Suranga; Moe, Sharon; Duke, Jon; Department of Medicine, IU School of MedicineIntroduction: CMS-2728 form (Medical Evidence Report) assesses 23 comorbidities chosen to reflect poor outcomes and increased mortality risk. Previous studies questioned the validity of physician reporting on forms CMS-2728. We hypothesize that reporting of comorbidities by computer algorithms identifies more comorbidities than physician completion, and, therefore, is more reflective of underlying disease burden. Methods: We collected data from CMS-2728 forms for all 296 patients who had incident ESRD diagnosis and received chronic dialysis from 2005 through 2014 at Indiana University outpatient dialysis centers. We analyzed patients' data from electronic medical records systems that collated information from multiple health care sources. Previously utilized algorithms or natural language processing was used to extract data on 10 comorbidities for a period of up to 10 years prior to ESRD incidence. These algorithms incorporate billing codes, prescriptions, and other relevant elements. We compared the presence or unchecked status of these comorbidities on the forms to the presence or absence according to the algorithms. Findings: Computer algorithms had higher reporting of comorbidities compared to forms completion by physicians. This remained true when decreasing data span to one year and using only a single health center source. The algorithms determination was well accepted by a physician panel. Importantly, algorithms use significantly increased the expected deaths and lowered the standardized mortality ratios. Discussion: Using computer algorithms showed superior identification of comorbidities for form CMS-2728 and altered standardized mortality ratios. Adapting similar algorithms in available EMR systems may offer more thorough evaluation of comorbidities and improve quality reporting.Item "I Am Interested!": The Voices of the Community and Their Participation in Health Advisory Boards(Mary Ann Liebert, 2024-01-08) Sotto-Santiago, Sylk; Wiehe, Sarah; Claxton, Gina; Stamper, Gavin; Delp, Lindsey; Hudson, Brenda; Lynch, Dustin; Moe, Sharon; Pediatrics, School of MedicineIntroduction: Researchers can often be challenged by meaningful efforts to involve the public and communities in research. Community and health advisory boards (HABs) offer an opportunity to create a fully intentional and honest relationship between researchers and the community. Objective: Most recently, the All Indiana (IN) for Health HAB had four openings and a call was published to our community of over 13,800 individuals in the All IN for Health newsletter. Four hundred eighty-eight individuals submitted applications to become part of the board. In what follows, we share the lessons in motivations and interests of individuals who responded. Methods: The application process included the following questions: What lived experiences and/or personal interests have motivated you to be involved in All IN for Health? Please explain why you are interested in being an All IN for HAB member. Our analysis approach was qualitative and centered on narrative research. Results: We organize the findings in two categories: Motivation and Interests. Individuals were motivated to participate based on family or friend diagnosis, personal diagnosis, roles as caregivers, desire to impact change and advocacy, role as health professional, and previous participation in research. Interests followed similar themes beginning with crediting their interest to a diagnosis. In addition, we categorized desire to share their experience, personal positionality, and previous research experience, and contributing to the education of student/trainee. Conclusion: By understanding motivations, we understand needs. This information can be used for other advisory boards, as well as recruitment into research participation and health care advocacy.Item Indiana CTSI Preclinical Innovation Think Tank Program(Association for Clinical and Translational Sciences, 2022-04-21) Portonovo, Padma; Garcia, Kara; Moe, SharonThe skills and knowledge required for successful commercialization of new technologies (intellectual property protection, SBIR/STTR funding, and startup creation) are very different than those for traditional academic research (scientific publication and R01-style grant funding). The Indiana CTSI Think Tank Program is designed to provide early guidance to academic and clinical investigators interested in advancing their discoveries to the market. The program is open to investigators from Indiana University (IU), Purdue University, or the University of Notre Dame; and includes a pool of advisors across these universities and industry around the state to provide investigators with a wide range of expertise and perspectives.