Exploring exercise behavior in pregnant and postpartum adolescents in Mississippi
Formative research to support obesity prevention interventions delivered through existing public health service programs that low-income pregnant and postpartum adolescents, such as WIC, is paramount. Thus, the goal of this two-year exploratory study is to identify modifiable psychosocial, cultural, and environmental factors related to exercise behavior in pregnant and postpartum adolescent (≤19 years) WIC participants in Mississippi. We aim to: (1) utilize qualitative (parent/guardian focus groups; WIC staff interviews; adolescent small group interviews; adolescent photovoice projects) and quantitative (adolescent-parent/guardian dyad surveys) methods to explore multi-level predisposing, enabling, and reinforcing psychosocial, environmental, and cultural determinants of exercise behavior during pregnancy and postpartum periods, and in the transitional phase from pregnancy to postpartum; and (2) objectively assess rural environmental supports for exercise using the Rural Active Living Assessment (RALA) tools and the Physical Activity Resource Assessment (PARA) tool.
The outcomes of this investigation will bolster a K01 proposal (PAR-16-211) to develop and test the effectiveness, feasibility, and acceptability of a theory-based, multimodal digital exercise intervention rural, low-income pregnant and postpartum adolescents in Mississippi using an effectiveness-implementation research design. This is an important and understudied line of behavioral intervention research to prevent pediatric obesity during critical developmental periods from pregnancy through adolescence.
Assistant Professor, RadiologyUMMC
Body Composition as a Biomarker of Obesity-Related Diseases in African-Americans
Dr. Howard-Claudio's proposal aims to characterize the body composition of a large cohort of African Americans to discern how anthropometric measures including SAD and waist circumference (WC) compare with VAT and/or fatty liver in their association with metabolic traits (fasting glucose, fasting insulin, HOMA-IR, lipid and cholesterol measures), and their ability to predict metabolic and CVD outcomes (e.g. incident type 2 diabetes, CVD events, and hepatic steatosis).
The overall intent is to identify reliable predictive measures of obesity-related diseases by assessing the correlation of SAD and CT imaging-derived measures of body composition and fat distribution to metabolic traits in African-Americans.
Assistant Professor, NeurosurguryUMMC
Modeling Leptomeningeal Metastasis using Breast Circulating Tumor Cell Xenografts
Leptomeningeal metastasis (LMD) occurs in up to 10% of solid tumors and 15% of hematologic malignancies, with an expected median survival of 3-16 weeks. Despite overwhelming associated morbidity and mortality, major gaps exist in the understanding of LMD, and therapeutic options are limited. In this 1- year pilot proposal, we will develop a circulating tumor cell (CTC)-based patient-derived xenograft (PDX) model of LMD in zebrafish. PDX models in zebrafish offer the benefit of high throughput, low cost, and the requirement for fewer input cells compared to other model systems. We will focus our efforts on 2 specific aims. First, using breast CTC isolates (BRx-42 and BRx-29, both derived from the peripheral blood of women with intracranial metastasis) that we have previously established and engineered to express luciferase and green fluorescent protein, we will perform intraventricular brain injections in zebrafish embryos 2 days post-fertilization. Subsequently, we will evaluate tumor cell growth and invasion in the zebrafish embryos, which are translucent, using fluorescence microscopy. Second, we will collect CTCs directly from the cerebrospinal fluid (CSF) of breast and lung cancer patients with LMD. Of note, CTCs from the CSF are routinely collected during clinical care of patients with LMD. Any excess CTCs will be labeled fluorescently with Dil and injected intraventricularly in zebrafish embryo brains 2 days post-fertilization. We anticipate obtaining CTCs from 5-10 patients during the 1-year pilot period. Tumor cell growth and invasion will be evaluated using fluorescence microscopy. During the 1-year funding period, we expect to achieve the development of these two systems as robust models of studying LMD. In follow-up studies, we will employ these models to 1) explore molecular pathways associated with the development of LMD using CRISPR/CAS9 whole-genome screening and 2) evaluate candidate therapeutics for LMD. We anticipate these studies will lead to high-profile publications and funded grant applications.
Assistant Professor, Public HealthUniversity of Southern Mississippi
Effectiveness of Community Health Workers in Reducing CVD in the Mississippi DeltaDr. Mayfield-Johnson’s research focuses on understanding and improving population health and reducing health disparities.
The goal of the pilot project is to assess the effectiveness of a CHW model on the continued care and management of cardiovascular disease among patients at federally qualified health centers (FQHCs) and community health centers (CHCs) in the Mississippi Delta. The MCCTR Pilot Project aims to systematically assess Community Health Workers’ impact on improving clinical outcomes, patient satisfaction, and reducing costs among patients at FQHCs and CHCs in the Mississippi Delta. These efforts are the next step towards evaluating the effectiveness of CHWs as a best practice intervention model for CVD-risk factors including obesity.
Professor, MathematicsTougaloo College
Uncovering and Understanding Population Differences with Topological Methods
Dr. Wang's pilot project uses topological data analysis and analytic tools to generate information for analysis to better describe the mechanisms of disease in the study population (JHS participants). The same disease may come from many different mechanisms but the underlying mechanism of the disease may determine the best treatment. The goal of the analysis is to break populations with complex diseases into mechanistically consistent subpopulations and propose treatments based on the mechanism.
Obesity, hypertension, renal disease, and a combination of the three are the result of distinct etiologies within the study participants. By analyzing aptamer, metabolic, and clinical data alone or in tandem, differences between populations will explain these etiologies.
The Chronic State of Obesity and the Acute Response to Sepsis
Obesity remains an epidemic facing modern health care. While the understanding of obesity as both a chronic disease and as a culprit in the development of numerous chronic diseases continue to grow, the effect of the chronic state of obesity on acute illness remains uncertain. Some investigations suggest an “obesity paradox” exists in acute illness, wherein overweight and obese individuals have more favorable prognoses than normal or underweight counterparts. In severe sepsis and septic shock, the effect of obesity on outcomes has been conflicting with some reporting higher rates of organ failure, ICU length of stay, and mortality in obese patients, while others show improved mortality in overweight or obese patients. The overarching hypothesis of Dr. Sterling’s work is that obesity results in a chronic state of inflammation which is protective at low to moderate levels of obesity during an acute physiologic stressor. Dr. Sterling aim’s to; determine if markers of inflammation are associated with the degree of obesity during infection without evidence of sepsis, sepsis, and septic shock as compared to matched controls, test if elevated adipokine levels decrease the progression of illness severity and improves patient-centered outcomes, and determine platelet microparticle formation and platelet function in sepsis and the association with adipokine levels in obese and non-obese matched cohorts.
Obesity-Associated Hypercoagulability in Trauma Patients
The primary research interest of Dr. Kutcher's career to date has been identifying biochemical mechanisms of coagulation abnormalities in injured patients. Understanding these phenomena will translate into avoidance of thromboembolic events related to later hypercoagulability. Obese patients are among the highest risk for these complications, due to baseline obesity-associated hypercoagulability compounded by frequent under-dosing of prophylactic heparinoids.
The over-arching hypothesis of Dr. Kutcher's MCCTR study is that circulating procoagulant MP mediate obesity-associated hypercoagulabilty after trauma. This finding would identify arrival MP level as an important tool to stratify trauma patients as low- versus high-risk for later thromboembolic complications, for which increased surveillance and/or more aggressive thromboprophylaxis regimens may be appropriate. The longitudinal data collection proposed here will also allow us to identify and assess the impact of inadequate dosage and timing of prophylactic heparinoid medications used to mitigate the risk of thromboembolic complications, which are frequently under-dosed in the obese population.
Director, Radiology ResearchBody and Oncologic Radiologist
Comparative Effectiveness of Noninvasive Tests for Staging Chronic Liver Disease
Dr. Smith's research focuses on identifying methods to non-invasively stage chronic liver disease in lean and obese patients. Chronic liver disease is clinically silent and can progress to irreversible cirrhosis which can in turn lead to liver cancer, liver failure and death. Chronic liver disease is more common, more severe, and more difficult to stage in obese patients. Treatment is based on the cause and stage of disease, and the reference standard for staging chronic liver disease is liver biopsy, though problems with the procedure include the invasive approach, sampling errors, subjectivity in pathologic staging, and complications such as pain, bleeding, infection and rarely death.
Dr. Smith is conducting a comparative effectiveness study whereby his team will prospectively compare the accuracy and technical success rate of several different noninvasive imaging techniques that can be used to stage chronic liver disease including ultrasound elastography, magnetic resonance elastograpy, and a computed tomography (CT) liver surface nodularity score. He hypothesizes that the CT liver surface nodularity score will have similar accuracy but a high technical success rate than competing noninvasive imaging techniques, especially in obese patients.