Assistant Professor, Internal MedicineUMMC
Effect of GLP-1 Receptor Agonists (glp-1) on Trabecular Bone Mineral Density and Visceral Adiposity in Postmenopausal Patients
Osteoporotic fractures occur in 1/3rd women over the age of 50 and are responsible for 609,000 DALY’s (Disability adjusted loss in years). Type 2 Diabetes mellitus (T2DM) is estimated to affect 25% of adults in the United states, and they experience a 20%-30%increased risk of osteoporotic fractures as compared to non-diabetics. In addition, to the increased co-prevalence of osteoporosis and T2DM conventional methods of diagnosing osteoporosis (measuring bone mineral density on a DEXA scan), often underestimate the fracture risk in T2DM as the bone mineral density is normal. Trabecular bone score is a non-invasive measure of bone microarchitecture. This has been shown to more accurately assess fracture risk in T2DM, than measurement of bone mineral density. Due to the increased co-prevalence of these two disorders, the effect of pharmacological agents used for the treatment of diabetes mellitus on bone metabolism has assumed importance. GLP-1 receptor agonists which have been approved for the treatment of type 2 diabetes mellitus have been shown to improve trabecular bone mass in animal studies.
Within his proposal, Dr. Garla hypothesizes that GLP-1 receptor agonists increase trabecular bone score by decreasing visceral fat, reduce the secretion of inflammatory mediators. This, decreases in secretion of inflammatory mediators leads to a decrease in bone resorption. He also hypothesizes that GLP-1 receptor agonists would decrease levels of sclerostin which is a potent inhibitor of bone formation. This, in turn would increase the levels of osteocalcin which is responsible for bone formation. He plans to conduct a non- randomized controlled trial by enrolling 24 post-menopausal patients over 55 years with a history of type 2 diabetes mellitus who are to be started on a GLP-1 receptor agonist with matched controls from the UMMC endocrine clinics.
Associate Professor, PsychiatryUMMC
Formative Research to Develop a Pediatric Obesity Primary Care Research Practice Network
Pediatric overweight and obesity impacts more than one in three children in the U.S.. Nationwide Mississippi has the highest rate of obesity in youth. Overweight and obesity in childhood have significant negative impacts on physical and psychological health and places a substantial burden on the health care system due to increased morbidity, mortality, and health care costs. There is a critical need for research focused on children who are overweight and obese in Mississippi to supplement current medical care and prevent the development of chronic health conditions.
Dr. Lim utilizes a mixed methods approach to fill these gaps in research and infrastructure. Parent surveys will be conducted with 100 parents/caregivers of youth 2 to 17 years of age who are overweight or obese. Her survey will assess interest in receiving evidence based pediatric obesity prevention and treatment in primary care settings, as well as perceived barriers and facilitators to participating in pediatric obesity focused clinical trials research. Pediatric primary care providers (n = 36) will participate in focus groups to examine knowledge of pediatric overweight and obesity expert prevention and treatment recommendations, as well as needs and interest for an obesity specific practice network and pediatric obesity clinical trials research. Results will inform the development and implementation of pediatric obesity clinical trials in primary care settings, as well as the creation of a research practice network.
Assistant Professor, Kinesiology and NutritionUSM
Physical Activity and Cardiometabolic Health in Children with Autism Spectrum Disorder
While it is established that cardiovascular disease (CVD) is typically associated with middle or old age, atherosclerosis often initiates in early childhood when deposits of cholesterol form fatty streaks in the intima of large arteries. This early initiation of the atherosclerotic process has been linked to cardiovascular risk factors such as obesity.
Dr. McCoy's project proposes to examine the associations between modifiable lifestyle behaviors and cardiometabolic health in youth with ASD, as well as determine the feasibility of using novel, non-invasive means to measure cardiometabolic health. Therefore, we propose the following aims: Aim 1: Examine the associations between lifestyle factors (body fatness, physical activity, and sedentary behavior with cardiometabolic health in children with ASD; Aim 2: Examine the feasibility of using applanation tonometry coupled with cuff oscillometry to measure arterial stiffness in children with ASD; and Aim 2b: Examine the feasibility of using the ActivPAL accelerometer to measure PA and sedentary behavior in children with ASD.
Associate Professor, Internal MedicineUMMC
Prospective Registry Study of Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension in Mississippi
Dr. Wells' proposal outlines the development of the first registry for PAH and CTEPH patients among affected Mississippians. Guidelines on the management of PAH and CTEPH largely stem from clinical trials and registry studies outside of Mississippi which challenges the external validity. Data from a Mississippi-based registry with give a more accurate description of the epidemiology of the disease which will direct screening practices, risk stratification and inform treatment approaches. Pulmonary arterial hypertension now has at least 20 possible PAH-specific medications that all address one of three possible molecular pathways. As the registry grows, unique factors among Mississippians that predict best treatment choices can be discerned through comparative effectiveness research. Precision medicine is being increasingly recognized as a more effective approach to patient care and this work serves as a foundation for further deep molecular phenotype understanding of PAH and CTEPH with tremendous potential to improve patient care.
Associate Professor, Kinesiology and NutritionUSM
Visual feedback monitoring during exercise in individuals with obesity
Dr. Oliveira's study is centered around the risks of major chronic diseases caused by obesity. The role of exercise has been shown to be particularly important in preventing weight gain or regain, and offering numerous health benefits for people with obesity. The American College of Sports Medicine (ACSM) guidelines for exercise prescription indicate specific exercise parameters (frequency, intensity, time, and type of exercise) for designing exercise programs for individuals with overweight and obesity. However, the correct implementation of these guidelines can be difficult for two reasons: 1) concepts such as %VO2 reserve (%VO2R), heart rate reserve (HRR) or % one maximum repetition (1-RM), might be difficult to interpret and apply independently by individuals not familiar with exercise prescriptions, and 2) they do not address specific exercise limitations in individuals with obesity. Specifically, the effort to meet moderate to vigorous intensity levels of exercise has the potential to lead to involvement in activities that involve high tibia peak positive accelerations (PPA) (e.g. running), which has been associated with increased risk of osteoarthritis in individuals with obesity. A visual feedback monitoring system (VFMS) has been developed. This system can be used to meet moderate to vigorous intensity levels of exercise by increasing maximum hip flexion while maintaining low tibia PPA during comfortable walking speeds. We will investigate two subgroups of individuals with obesity: sedentary and active. Target heart rates of 40% and 60% HRR will be used as the exercise intensities. We will examine energy expenditure, heart rate, and kinematic measures. The objective of this project is to determine the effect of exercising with the VFMS in individuals with obesity (Aim 1), and compare the effect of the VFMS between active and sedentary individuals with obesity (Aim 2). This pilot study will allow the streamlining of the VFMS and exercise protocol. Moreover, the results of this study will inform proposals for larger interventions that will focus on testing the effectiveness of the VFMS in individuals with different types of obesity and with osteoarthritis.
Assistant Professor, Pharmacology and ToxicologyUMMC
Progesterone and PIBF: New Insights for Treatment Options for Preeclampsia
Dr. Amaral's project is centered around evaluating whether progesterone supplementation (in the form of 17-hydroxyprogesterone caproate (17-OHPC) stimulates Progesterone Induced Blocking Factor (PIBF) as a mechanism to improve the pathophysiology of preeclampsia in the presence and absence of obesity. Preeclampsia (PE) affects 5-7% of all pregnancies in the U.S. Despite being a leading cause of maternal death and perinatal morbidity, the mechanisms responsible for the pathogenesis of PE are unclear. Hypertension associated with PE usually develops during the late second or third trimester of pregnancy and remits after delivery, implicating the placenta as a central culprit in the disease. Studies have shown that a healthy pregnancy is associated with elevations in progesterone and TH2/uterine, NK (non-cytolytic) profile favoring feto-immunotolerance. An important anti-inflammatory protein secreted from progesterone stimulated lymphocytes is PIBF-progesterone induced blocking factor. Importantly, previous studies have shown that obese pregnant women had lowered progesterone levels compared to non-obese pregnant women. Moreover, our PE patient population delivering at the UMMC Wiser hospital have significantly lower circulating progesterone compared to non-hypertensive normal pregnant women. Collectively these data suggest that obesity and PE are both independent factors that cause lower progesterone and thus PIBF during pregnancy. In fact, the preliminary data shows decreased circulating PIBF in UMMC PE patient population. Although PIBF has been shown to stimulate TH2 lymphocytes secreting IL-4 we do not know a role for progesterone supplementation (in the form of 17-hydroxyprogesterone caproate (17-OHPC) to stimulate PIBF as mechanisms to improve the pathophysiology associated with PE in the presence or absence of obesity. The overarching hypothesis is that lower level of progesterone could lead to lower PIBF which could lead to increased TH1 and NK causing elevated vasoactive factors (sFlt-1, ET-1/ decreased NO) thus contributing to the development of hypertension during pregnancy. Indeed, this pathway could be exacerbated during obesity associated with PE. The objectives of this pilot project will determine if obesity exacerbates decreases in circulating progesterone/PlBF, TH2s and IL-4 which is associated with increased sFlt-1/ET-1 and decreased NO during PE and compared to obese and morbidly obese PE participants (Aim 1). Furthermore, the second aim will examine if 7-OHPC supplementation stimulates PIBF/IL-4/TH2, as a mechanism of reducing NK/TH1s, sFlt-1, ET-1 and improves NO and blood pressure in PE associated with obesity (Aim 2).
Assistant Professor, PediatricsUMMC
Obesity in Pediatric Sickle Cell Disease: A New Phenomenon
Dr. Jackson's proposal is centered around obesity in the pediatric sickle cell population in Mississippi. Historically, patients with SCD had a higher basal metabolic rate (measured by resting energy expenditure) and were underweight. Patients with SCD, therefore, did not typically experience obesity-related co-morbidities, such as hypertension, hyperlipidemia and hyperglycemia. Recent research describes increased rates of overweight and obesity in both pediatric and adult patients with SCD. This increase in weight status is likely due to improvements in medical management but may also be due to increased caloric intake and decreased physical activity, similar to trends in the general population. The objective of this project is to address the current gap of whether overweight and obese pediatric patients with SCD have weight-related co-morbidities. The central hypothesis of this study is that pediatric patients with SCD who are overweight/obese will have increased risk of hypertension, hyperlipidemia and hyperglycemia compared to underweight/normal weight counterparts, and that diet, exercise, and family medical history will be associated with outcomes. This project will examine the prevalence of hypertension, hyperlipidemia and hyperglycemia in pediatric patients with SCD who are overweight/obese compared to their underweight and normal weight counterparts (Aim 1). This project will also examine the impact of diet, exercise and family medical history on the prevalence of overweight/obesity, hypertension, hyperlipidemia and hyperglycemia in pediatric patients with SCD (Aim 2). This is a significant, novel, and clinically relevant study as it has only very recently been documented that patients with SCD now have similar rates of overweight/obesity as those without SCD. It will be an important next-step to examine if pediatric patients with SCD and overweight/obesity are at increased risk of weight-related complications (i.e., hypertension, hyperlipidemia and hyperglycemia). This new knowledge can lead to updated screening recommendations, earlier detection, earlier treatment, and increased prevention measures.
Assistant Professor, Neonatal MedicineUMMC
Outcomes Prediction in Neonates with Surgical Necrotizing Enterocolitis Combining Clinical,Histopathological and Genomic Markers
Dr. Garg's proposal focuses on how Necrotizing enterocolitis (NEC) is a devastating acute gastrointestinal illness of the neonatal period, affecting about 5-10% of premature infants with birth weight of ≤1500 grams. Despite major advances in neonatal intensive care and reductions in all-cause mortality among premature infants, NEC continues to be associated with mortality rates of 25-40%. Unfortunately, the ability to predict the clinical outcomes in NEC is limited. The development of accurate prediction models for NEC outcomes can address an unmet clinical need in neonatology, as this information could allow timely transfer to a regional referral center, early institution of multi-modality monitoring, focused treatment, enrollment in clinical trials, and appropriate counseling for the families. Given that no NEC studies to date have utilized genomic analysis in these predictive models, this project proposes that the inclusion of genomic information, namely the evaluation of immune transcriptome profiling of tissue biopsies (from surgical interventions) will greatly enhance these models. Thus, this study is addressing the hypothesis that the accuracy of NEC clinical outcome prediction will be vastly improved by combining clinical, radiological, histopathological, and genomic information.
Assistant Professor, Medicine - Infectious Diseases
Optimal Timing of Device Removal in Patients with Cardiovascular Implantable Electronic Device Infections: A Multicenter Analysis
About 6.2 million adults in the United States live with advanced heart failure, and particularly for the state of Mississippi, this remains the leading cause of death accounting for over a third of all deaths in the state. Cardiovascular implantable electronic devices (CIED) have become critical in the management of cardiac disease. However, with expanding indications, recent data suggest a disproportionate increase in the rate of CIED infections, a complication associated with significant morbidity, mortality, and high cost. Important patient-related factors for CIED infection include body mass index >25 kg/m2, diabetes mellitus and renal dysfunction. However, these infections remain largely understudied in racial/ethnic minority and underserved groups. Management of these infections warrants complete removal of the infected device (including cardiac leads) and pathogen-directed antimicrobial therapy to achieve attempted cure. However, the optimal timing of device removal in these cases remains unknown. Consequently, recommendations on the timing of device extraction are made on a case-by-case basis and left to the discretion of the treating physician. Delayed source control, however, may lead to worsening sepsis, multiorgan failure, distant seeding of infection in other organs in those with persistent bacteremia, and death. Although extraction procedures are not without risks, previous studies have shown that the mortality associated with CIED infection in patients treated with antibiotic therapy alone is up to 60% compared to 18% in those treated with device extraction, outweighing procedural risks. At present, there is no established criteria to assist the providers in defining the subgroup of patients at higher risk of complications and mortality who would benefit from early device extraction. Studies conducted in patients with central venous catheter-associated Gram-negative bacteremia have shown that delayed removal of the infected line particularly in those with multi-drug-resistant organisms and chronic renal failure were associated with increased 30-day mortality We hypothesize that a clinical prediction rule for use in patients with CIED infection will help stratify cases regarding the timing of device extraction and improve outcomes by providing evidence-based care. Furthermore, early device removal may increase survival and decrease the associated economic burden on hospitals and the healthcare system by reducing the length of hospital stay.
Associate Professor, Neurobiology and Anatomical SciencesUMMC
Glucagon-like Peptide 1-mediated Mechanisms of Metabolic Dysfunction after Spinal Cord Injury in Humans
Individuals living with a spinal cord injury (SCI) in the U.S. are at increased risk for metabolic disease including sarcopenic obesity, type-2 diabetes mellitus, cardiovascular disease, and dyslipidemia. The increased risk for metabolic dysfunction is thought to be the result of reduced physical activity due to paralysis; however, even when accounting for inactivity, there remains a substantial gap in understanding the physiologic basis of metabolic disease after SCI. In a series of rodent studies, we identified a promising hormonal target that may unify both our diverse rodent data and human reports in the literature concerning glycemic dysregulation after SCI. These pre-clinical data implicate the glucagon-like peptide 1 (GLP-1) system as a putative signaling target behind the metabolic dysfunction after SCI. Indeed there is a robust literature connecting GLP-1 with body-weight regulation, glycemic action in the central nervous system and periphery, neuroprotection, and immune modulation. Our long-term plan is to extend our novel pre-clinical work to further the understanding of glycemic control which changes are leading to metabolic disease in individuals with SCI. Our central hypothesis is that SCI itself drives whole-body remodeling of the GLP-1 system, which causes GLP-1 dysregulation and makes it one of the key contributors to the development of metabolic dysfunction in the SCI population. In this proof-of-principle, first-in-human study, our working hypothesis is that GLP-1 dysregulation after SCI causes uncoupling of the normal actions of GLP-1, as evident following glucose challenge while accounting for body composition. Our aim is to determine if fasting and glucose-elicited levels of GLP-1 differ between individuals with subacute SCI, chronic SCI, and non-injured controls. The obtained results are expected to generate pivotal preliminary data that will critically inform directions for future rodent and human investigations and constitute basis for obtaining competitive funding.
Association between Weight for Length and Severity of Bronchopulmonary Dysplasia
Premature infants born at less than 30 weeks of gestation are at high risk for bronchopulmonary dysplasia. In a large cohort of children who are overweight/obese with and without asthma, a significant correlation was noted between obesity and abnormal pulmonary functions. Through his pilot project, Dr. Alur is exploring whether weight for length measurements are associated with higher respiratory severity scores among premature infants. Additionally, he will also explore whether there is a correlation between total calories and/or protein with weight for length status.
Associate Professor, Data Science
Development of the UMMC BioBase
Dr. Showmaker's proposal supports the development of software tools to analyze and visualize Omics derived datasets in a supercomputing environment. The supercomputing environment is needed to process and merge the abundant big data sets generated by today’s modern Omics technologies such as genomics, transcriptomics, proteomics, and metabolomics. This project is being conducted in 2 phases; phase 1 entails the creation of a novel biological database (named UMMC BioBase) and associated computational methods for data import and analysis (Aim 1). The UMMC BioBase will include curated publicly available data sets including knowledge bases, gene expression datasets and genome wide association studies. Additionally, datasets from national repositories and biological consortiums will be included in the UMMC Biobase including those available from the National Institutes of Health’s National Center for Biotechnology (NCBI) and European Bioinformatics Institute (EMBL-EBI). Phase 2 focuses on applying data science methodologies such as graph theory, machine learning, and artificial intelligence to the data within the UMMC BioBase to investigate clinical and biological problems (Aim 2). In phase 2 translational datasets will be analyzed including those related to racial health disparities as well as other UMMC Mississippi Center for Clinical and Translational Research mission critical datasets for obesity, heart disease, chronic kidney disease, and those generated by UMMC-MCCTR investigators. The adaptation and development of biological-based supercomputing tools will allow UMMC/MCCTR investigators to do more with the data they generate and provide a platform for future bioinformatic investigations.
Assistant Professor, Preventive MedicineUMMC
Mapping Informal and Formal Food Outlets to Address Obesity and Food Insecurity
Dr. Compretta's project focuses on exploring previously unexamined informal food outlets in addition to more traditional, formal food outlets to systematically describe food access issues and obesity risk in West Jackson, Mississippi, an urban food desert. Her project seeks to accomplish the following aims: (1) characterize formal and informal food sources in an African American urban population in the Deep South with a high risk for obesity, and (2) identify food source usage patterns and selection factors in the target community. Her project employs a mixed methods convergent parallel study design that includes both GIS techniques, surveys, inventories, and qualitative focus groups and interviews within a community-engaged research framework. The overall objective of the proposed project is to characterize and evaluate food resources in a high-risk neighborhood to shed light on previously unidentified informal food venues and their relationships to food access, choice, and obesity risk. The data produced from this exploratory project will create an evidence-based foundation for developing larger studies and interventional strategies that address the individual and structural barriers that limit healthy food availability and access in the target community. The project will also increase knowledge regarding how best to design future interventional studies to increase healthy food access and behaviors and decrease obesity risk.
Assistant Professor, SurgeryUMMC
Adipose Tissue Effects on Cardiac Surgery Outcomes (ATECO)
Obesity is a well-established risk factor for multiple cardiovascular disease including: coronary artery disease, hyperlipidemia, hypertension, and diabetes. At least, 35% of Mississippi residents are obese according to the Centers for Disease Control. The goal of Dr. Copeland’s study is to describe and test the predictive power of a more informative definition of obesity using a prospective trial of all consecutive patients aged 18-80 undergoing elective and urgent cardiac surgery at the University of Mississippi Medical Center. Subjects will have obesity described via biometric measurements (waist and hip circumferences), functional status will be assessed, and adipose tissue biomarker profiles. The primary endpoint will be clinical outcomes of cardiac surgery in the immediate post-operative period (within the first 30 days after surgery) and long-term (within in the first year after surgery). The secondary outcomes include: in-hospital mortality, intensive care unit (ICU) length of stay, hospital length of stay, 30-day, 1-year survival and rate of re-admission. Also included will be length of time on respiratory support (prolonged ventilation greater than 24 hours), new onset acute renal failure, superficial wound infection, sternal wound infection, stroke, atrial fibrillation and disposition on discharge (discharged to home, home with home health, transfer to a rehab or nursing facility).
Professor, Pharmacy AdministrationUniversity of Mississippi (Oxford campus)
Patient Perceptions of and Attitudes toward a Weight Management Program Offered by Community Pharmacies
Dr. Rosenthal’s project aims to determine the weight management knowledge, and design, of a weight management program to be delivered in a community pharmacies in Mississippi. Patients’ perspectives will be obtained through five focus group interviews with 50 patients from four communities in northern and central Mississippi. The proposed study will provide a list of weight management program characteristics including kinds of advice and program design components that are currently unavailable in the weight management literature.
Assistant Professor, Population Health ScienceUMMC
Survivor Heart: Improving Cardiovascular Outcomes in Breast Cancer Survivors
More than 3 million women in the US are breast cancer survivors. African American breast cancer survivors have a disproportionately high burden of CVD mortality. The elevated CVD mortality rate among African American breast cancer survivors is due in part to multiple, modifiable CVD risk factors that are disproportionately high in this group, such as hypertension, obesity, diabetes, and physical inactivity. A population-specific CVD risk reduction intervention that is delivered via telehealth technology may be an effective way to reduce the CVD risks of African American breast cancer survivors living in rural and medically underserved areas of Mississippi. The overall goal of Dr. Williams' study is to develop a CVD risk reduction telehealth intervention that is tailored for African American breast cancer survivors.
Professor, Psychology University of Southern Mississippi
Mechanisms of change in parenting programs to prevent childhood obesity
Dr. Dufrene's project focuses on parental influences of children’s health. He aims to test the effects of modified Parent-Child Interaction Therapy (PCIT) on health measures of behaviors that tend to cause obesity, determine agents of change that may explain the PCIT’s influence on behaviors that tend to cause obesity, and evaluate the social validity of PCIT using rating scales completed by parents and interviews using qualitative analytic methods.
The overall goal of the project is to obtain a better understanding of why evidence-based parenting programs impact negative health behaviors related to obesity and disentangle the relationships among these potential mechanisms of change.
Assistant Professor, MedicineUMMC
Remote Hypertension Management Using Home Blood Pressure Telemonitoring and a Standardized Treatment Protocol
Assistant Professor, KinesiotherapyUniversity of Southern Mississippi
Electrically Induced Cycling and Nutritional Counseling for Counteracting Obesity after SCI
Dr. Dolbow's research focus is on the use of activity-based restorative therapies to reverse unhealthy body composition changes and the increased cardiometabolic disease risk that take place after spinal cord injury. Specifically, decreasing body fat, increasing skeletal muscle, improving vascular health and circulation, and improving blood lipid and and glucose profiles. Restoration of body composition to healthy proportions of muscle and fat and enhancing peripheral vascular health is important for improving mobility and decreasing cardiometabolic disease risk. Dr. Dolbow has developed a resistance-guided high intensity interval training functional electrical stimulation cycling protocol, which has been been shown in preliminary studies, to increase muscle mass in paralyzed legs, while improving cardiometabolic health markers in obese individuals with spinal cord injury. The research aim for Dr. Dolbow’s group was to determine preliminary efficacy of the new electrically induced cycling protocol combined with nutritional counseling in obese adults with chronic spinal cord injury.