UTMB Health SHARED
UTMB Health SHARED is an online community space for Scholarship, Historical Archives, Repository, & Electronic Dissertations. This digital service is an important tool for preserving the organization’s legacy and facilitating scholarly communication.
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- Completed capstone projects from students of the School of Health Professions
- Publications by degree candidates from the Graduate School of Biomedical Sciences, the School of Nursing, and the School of Public and Population Health
- Profiles of UTMB faculty and staff, including selected works.
- Historical images and documents from Moody Medical Library special collections
- Public documents produced by university departments
Recent Submissions
The Prevalence of Cardiovascular Disease and Associated Risk Factors among Sexual and Gender Minorities in Texas: Behavioral Risk Factor Surveillance System 2015, 2017, and 2019
(2023-05) Rodriguez, Robert Anthony 1989-; John D. Prochaska; Xiaoying Yu; Kyriakos S. Markides; Jason Flatt; Adrian Juarez
Sexual and Gender Minorities (SGM’s), commonly referred to as the LGBTQ+ community, have a higher prevalence of cardiovascular disease than their cisgender heterosexual peers in the United States. In addition, there is mounting evidence that suggests SGM adults have an increased exposure to cardiovascular disease risk factors throughout their lifespan, and these exposures are further exacerbated by negative experiences associated with minority stressors. Texas is home to the second-largest SGM population, however due to a lack of state-level data collection on sexual orientation or gender identity, very little is known about the well-being of this population. The purpose of this dissertation is to determine the prevalence of cardiovascular disease and associated risk factors between SGM’s and non-SGM (or cisgender, heterosexual) persons in Texas by investigating cross-sectional data from the Behavioral Risk Factor Surveillance System (BRFSS) in 2015, 2017, and 2019. Results showed that SGM Texans reported had similar rates of self-reported cardiovascular disease compared to non-SGMS. However, adult respondents who identified as an SGM, who were older, racial and ethnic minorities, current smokers, had more than one healthcare provider and were unable to afford healthcare in Texas were more likely to self-report having a cardiovascular complication.
Congenital Chagas Murine Model Development and Nanovaccine Efficacy Against Maternal-fetal Trypanosoma cruzi Pathogenesis
(2023-08) Rios, Lizette E 7/17/1989-; Ramkumar Menon, PhD; Nisha Garg, MBA, PhD; Ramkumar Menon, MS, PhD; MinKyung Yi, PhD; Antonio Ortega-Pacheco, PhD, MVSc, FRVCS, DVM; Imran Chowdhury, PhD
Maternal infection with Trypanosoma cruzi (Tc) parasite can lead to the vertical transmission from mother to fetus known as congenital Chagas’ disease (cCD). The objective was to develop a murine model of cCD to test the efficacy of a DNA nanovaccine developed by our laboratory. In this dissertation, we demonstrate that Tc infection in female mice delayed the initiation of pregnancy, reduced fertility rate, and resulted in vertical transmission of the parasite to the offspring. Pups born to infected dams showed lower survival rates, decreased birth weights, and impaired growth rates. Moreover, these pups exhibited significantly elevated levels of inflammation, necrosis, and fibrosis in their cardiac and brain tissues. A higher initial dose of the parasite had more detrimental effects on both fertility rates and the health of the pups, regardless of whether the dams were acutely or chronically infected. We have also established that Tc infection triggered delayed and insufficient activation of T cells, resulting in low levels of effector molecules that are needed for controlling the spread and replication of the parasite in both pregnant and non-pregnant dams. The nanovaccine showed enhanced immunity in pregnant mice compared to non-pregnant mice. Following challenge infection, the vaccine effectively enhanced the splenic differentiation, maturation and polyfunctional activation of CD4+ and CD8+ effector/effector memory and central memory subsets, with increased production of interferon gamma, perforin and granzyme B that exhibit cytolytic activities against the infected cells. Further, nanovaccine immunized pregnant mice exhibited effective control of the parasite burden in maternal tissues and inflammatory infiltrate, necrosis, and fibrosis in maternal (heart, skeletal muscle) and fetal placentas. Consequently, maternal fertility rate and pregnancy outcomes were improved in vaccinated infected mice. Together, we demonstrate that nanovaccine offers a valid strategy to elicit protective immunity against Tc infection during pregnancy, leading to improved control of maternal Tc infection and favorable fetal outcomes.
MicroRNA-122 and Poly(C)-Binding Protein 2 Bind to the Hepatitis C Virus Genome, Regulating Viral Replication and Genome Structure
(2023-08) Scott, Seth Dylan May 5th 1993-; Smith, Thomas; Choi, Kyung; Morais, Marc; Kuyumcu-Martinez, Muge N.; Lemon, Stanley M.
Hepatitis C virus (HCV) has a positive-sense RNA genome which is used as the template for both viral translation and negative-strand RNA synthesis. As both processes work in opposite directions on the genome the virus requires a mechanism to coordinate what process is acting on a given copy of genome. It has been suggested that the host factors, microRNA-122 (miR-122) and poly-(C) binding protein 2 (PCBP2), may regulate these two processes. These host factors promote HCV replication and compete for overlapping binding sites on the 5’ untranslated region (UTR) of the HCV genome. This work investigates how miR-122 and PCBP2 bind the 5’ UTR of the HCV genome, and how the competition between the two factors regulates viral translation and replication.
The binding competition of miR-122 and PCBP2 was characterized and the impacts on HCV replication identified. Near the 5’ terminus of the HCV genome there are two miR-122 binding sites, S1 and S2. PCBP2 binds a sequence that overlaps the second miR-122 binding site (S2) causing direct competition with miR-122 for binding. Steady-state binding assays determined that PCBP2 and miR-122 have similar affinities for the overlapping binding sites. Electron microscopy shows the competition of these two factors modulates the PCBP2-mediated circularization of the HCV genome. Additionally, a novel interaction between the viral polymerase, NS5B, and the 5’ UTR was shown. The affinity of this interaction is increased by miR-122 binding to HCV, potentially promoting RNA synthesis. The modulation of genome structure and polymerase affinity may form a mechanism by which the competition of miR-122 and PCBP2 regulates genome templating for translation versus RNA synthesis.
The structure of the miR-122 and HCV genome was investigated. The first miR-122 binding site (S1) is the higher affinity of the two sites and is not affected by PCBP2 binding. To determine the structure of the RNA complex via cryo-EM, a proheadRNA-Assisted RNA Imaging Scheme (pARIS) was developed. This novel method can be applied to other small RNA structures that otherwise cannot be reconstructed via cryo-EM. We found that the HCV:miR-122 complex is flexible and accessible in the absence of the argonaut-2 protein.
INVESTIGATING SEX DIFFERENCES IN THE TRANS-SYNAPTIC REGULATORS OF MESOLIMBIC DRIVEN PALATABLE FOOD INTAKE
(2023-05) Ogunseye, Kehinde Olusola; Hommel, Jonathan (jdhommel@utmb.edu); Spencer, Sade; Houghton, David; Buffington, Shelly; Anastasio, Noelle
Food intake is a coordination of elaborate sensory and motor actions that are influenced by multiple internal and external determinants but when dysregulated can result in feeding pathology. The overconsumption of highly palatable food is an important component of obesity, binge-eating disorder, and bulimia. Women and men observably experience differences in these diseases, underscoring a gap in understanding sex differences as a neurobiological factor that impacts motivated feeding behavior. In our pre-clinical studies, we employed a within-session behavior economics paradigm to tease apart several measurements of demand: hedonic set point (Q0), demand elasticity (α), P Max (elasticity defense), and essential value (reinforcement strength) of high-fat and standard food in free feeding and mildly restricted contexts in female and male mice In addition, we evaluated the effects of an anti-obesity drug, phentermine on these motivated feeding parameters. In our hedonic feeding conditions, we observed demand values are affected differently depending on sex and diet or a main effect of sex. In our homeostatic feeding conditions, we observed that the effects on the demand values were driven individually by factors of either sex or background feeding diet. During phentermine administration we observed similar trends in striking decreases in overall high-fat food demand in both sexes, but notably the reinforcement strength of the palatable food reward was not as steeply affected in female mice as seen in the male mice. In our circuitry experiments, we utilized a dual viral trans-synaptic strategy to trace upstream afferents of the mesolimbic pathway in male and female rats. Surprisingly these experiments revealed different afferent pathways in male and female groups. Female afferents of the mesolimbic pathway were labeled: BNST VTA NAcSh, while male afferents labeled: LSN + BNST VTA NAcSh. Furthermore, in situ hybridization analyses showed different estrogen receptor α distributions in the LSN and BNST in male and female that perhaps complement our palatable food intake studies of estrogen infusion into the LSN. In a cumulative analysis of these studies, we contend that mesolimbic driven motivated feeding behavior is potentially differently expressed as a result of sex dependent dimorphic hedonic circuitry.
Patterns, Variation and Mental Health Impact of Opioid Prescribing after Burn Injury
(2021-12) Polychronopoulou, Efstathia
Burn injury is a severe trauma that can cause debilitating pain, disability and declines in mental health and overall quality of life. Opioids are the mainstay therapy for management of pain after burn injury. In light of the opioid epidemic in the United States and the increased risk of harm associated with use of opioids, we sought to explore the trends, predictors, and impact on mental health of opioid prescribing after burn trauma, using a national commercial insurance database. First, we assessed the trends in opioid prescribing after burn injury in the outpatient setting and explored age, severity, and geographical variation. We found that opioid prescribing declined significantly between 2007 and 2017, however the rates of decline varied significantly among age groups, regions, and injury severity, with patients > 50, the South, and those with more severe burn realizing the least reductions in opioid prescriptions over time. Second, we assessed the rate of prescribing of gabapentinoids, alone or with opioids, over time to determine whether they were used as substitutes for opioid therapy. We found that gabapentinoid prescriptions alone increased significantly between 2012-2018, particularly among those over 50 years old, those residing in the South and the patients with less severe burns. Co-prescriptions with opioids did not differ significantly over time, after adjustment. Finally, we assessed the impact of opioid use on new onset depression, generalized anxiety or post-traumatic stress disorder in the post-burn period. We found that opioid prescribing after burn did not increase the risk for any mental health disorders, however those receiving opioids before burn were significantly more at risk to present with mood or stress disorders afterwards. Our findings support the need for uniform guidelines for the management of burn pain that promote non-opioid alternatives, as well as regular and timely screening for mental health problems in survivors of severe burn injury.