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Recent Submissions

The Interaction Between Arterial Stiffness, Amplitude of Cerebral Blood Flow Oscillations, and Cerebral Tissue Oxygenation
(2024-05) Hudson, Lindsey M.; Rickards, Caroline A.; Tune, Johnathan D.; Dick, Gregory M.
Inducing 0.1 Hz (10-s cycle) oscillations in cerebral blood flow attenuates the reduction in cerebral tissue oxygenation during simulated hemorrhage in humans. Our laboratory has developed a potential therapeutic technique called pulsatile perfusion therapy (PPT) which induces 0.1 Hz oscillations in cerebral blood flow. It is unknown, however, how stiffness of the arteries influences the magnitude of cerebral blood flow oscillations, and/or the protection of cerebral tissue oxygenation. When 0.1 Hz oscillations are induced during simulated hemorrhage, we hypothesized that: 1) arterial stiffness of the internal carotid artery (ICA) and common carotid artery (CCA) would increase from rest; 2) the amplitude of 0.1 Hz oscillations in cerebral blood flow would be higher in individuals with stiffer arteries, and; 3) the reduction in cerebral tissue oxygenation would be smaller with higher amplitude of cerebral blood flow oscillations. Two studies using two different techniques of PPT were performed to investigate these hypotheses. Study 1: In a retrospective analysis, 8 healthy human participants (age: 30.1±7.6 y) underwent a 10-min hypovolemic oscillatory lower body negative pressure (OLBNP) protocol, where chamber pressure oscillated every 5-s between -30 mmHg and -90 mmHg (i.e., 0.1 Hz). ICA β-stiffness index was calculated from measurements of ICA diameter (via ultrasound imaging), and arterial pressure (via finger photoplethysmography). Middle cerebral artery velocity (MCAv) was measured using transcranial doppler ultrasound, and cerebral tissue oxygenation (ScO2) was measured with near infrared spectroscopy. Fast Fourier transformation was used to quantify oscillations in mean MCAv at ~0.1 Hz. While mean MCAv 0.1 Hz oscillations increased from baseline to OLBNP (N=8, 34.0±33.9 (cm/s)2 vs. 104.7±58.1 (cm/s)2, p=0.01), ICA β stiffness did not increase (N=5, 6.1±0.7 au vs. 8.2±2.7 au, p=0.21). There was no relationship between baseline ICA β-stiffness and the percent change in mean MCAv 0.1 Hz oscillations (N=5; r=0.44, p=0.46). ScO2 decreased from baseline to OLBNP (N=8, 66.5±2.9 % vs. 64.8±2.9 %, p=0.03), but there was also no relationship between the percent change in mean MCAv 0.1 Hz oscillations and the decrease in ScO2 (r=0.28, p=0.50). Study 2: In a prospective pilot study, 3 participants underwent a 10-min LBNP protocol to a chamber pressure of -60 mmHg, and hemodynamic oscillations were simultaneously induced with bilateral thigh cuffs inflating for 5-s to 230 mmHg then deflating for 5-s in a 10-s cycle (i.e., 0.1 Hz). β-stiffness index of the CCA was measured. In this pilot study, insufficient data were collected to perform statistics for each of the three aims, so descriptive results are presented. Adequate ultrasound measurements were made for assessment of CCA β- stiffness in two participants; in the control condition, CCA β-stiffness was 6.7 ± 2.4 au during baseline and increased to 7.4 ± 1.1 au during LBNP (N=2). With PPT, CCA β-stiffness was 6.6 ± 1.6 au during baseline and increased to 7.8 ± 2.2 au during LBNP (N=2). The amplitude of MCAv 0.1 Hz oscillations increased from 7.9 (cm/s)2 at baseline of the control condition to 179.8 (cm/s)2 (i.e., a ~23-fold increase) during LBNP. The amplitude of MCAv 0.1 Hz oscillations increased from 25.8 (cm/s)2 during baseline of PPT to 210.2 (cm/s)2 (~8-fold increase) during LBNP (N=1). ScO2 decreased from 75.0% to 71.3% during LBNP in the control condition, and from 73.4% to 71.6% in the PPT condition (N=1). Based on the results of Study 1, 0.1 Hz OLBNP does not increase ICA stiffness, and there is no relationship between ICA stiffness, amplitude of induced 0.1 Hz cerebral blood flow oscillations, and the reduction in cerebral tissue oxygenation during simulated hemorrhage. However, as this analysis was performed retrospectively, and arterial stiffness was not initially an outcome measure, there were limited data available for analysis. For Study 2, we were successfully able to induce 0.1 Hz oscillations in cerebral blood flow by combining LBNP with bilateral thigh cuff inflations. However, insufficient data were available to make definitive conclusions about the role of PPT on CCA β-stiffness, 0.1 Hz oscillations in cerebral blood flow, or the relationship in 0.1 Hz oscillations in cerebral blood flow and protection of cerebral tissue oxygenation. This study is currently ongoing, and additional data will provide further insight into these relationships.
New Insights into the Roles of Glutaredoxins in the Lens
(2024-05) Zhang, Jinmin; Wu, Hongli; Ellis, Dorette Z.; Green, Kayla; Prokai-Tatrai, Katalin; Yan, Liang-Jun
Glutaredoxins (Grxs) play a crucial role in reversing protein glutathionylation. Glutaredoxin 1 (Grx1) and Glutaredoxin 2 (Grx2) are two main members of Grxs. Our prior studies have demonstrated that the Grx1 and Grx2 double knockout (DKO) mice develop cataracts prematurely at three months of age, and they are more susceptible to UV radiation. Therefore, these findings have highlighted the importance of Grx1 and Grx2 in preserving the transparency of the lens. However, the precise mechanisms underlying the faster development of cataracts in response to simultaneous deletion of Grx1 and Grx2 remain unknown. Lens epithelial cells (LECs) are pivotal for preserving lens transparency and overall lens functionality. Consequently, a comprehensive understanding of the antioxidant defenses and cell repair mechanisms in LECs is vital for cataract prevention and treatment strategies. We hypothesized that the absence of Grx1 and Grx2 could alter LECs function, triggering cataractogenesis. To test the hypothesis, we isolated primary LECs from WT and DKO mice and conducted a range of in vitro experiments to assess the effects of Grxs deletion on the epithelial phenotype, cellular proliferation, apoptosis, and mitochondrial function in LECs. We also conducted histology analysis of lens tissues using hematoxylin and eosin (H&E) staining. Our results revealed that Grx1 and Grx2 deficiency altered epithelial phenotype, reduced proliferation rate, and aberrant cell cycle distribution of DKO LECs compared to WT LECs. The deficiency also induced cellular senescence in cultured DKO LECs, which is consistent with our H&E staining data showing that LECs in the lens tissue from DKO mouse had accelerated senescence. Additionally, DKO LECs displayed compromised mitochondrial function and a compensatory metabolic shift towards glycolysis, indicating an adaptive response to Grx deficiency. Importantly, we also found that the OHPy2N2 activated Grxs and prevented the lens from H2O2-induced lens opacification. In conclusion, the findings in this study indicate that Grxs are important in regulating the aging process in the lens. Compounds that can activate Grxs may be promising candidates for preventing cataracts.
Assessment of Digit Skin Temperatures Via Infrared Thermography Under Different Climatic Conditions
(2024-05) Boettger, Chloe E.; Maddux, Scott D.; Cho, Elizabeth; Romero, Steven A.
The responsiveness of the manual/pedal digits (i.e., finger/toes) to temperature changes makes them valuable indicators of thermoregulatory function. Further, while infrared thermography is used in many medical settings, its utility in assessing acute changes in digit skin temperatures remains poorly established. Accordingly, this research investigated the use of forward-looking infrared (FLIR) imaging as a methodological tool for analyzing digital skin temperatures across varying climatic conditions. A Teledyne FLIR E76 camera and associated FLIR Studio software were used to assess peripheral digit skin temperatures in a sample of 10 living human subjects (3 female, 7 male). Images of each hand and foot were captured every 5 minutes over a 45-minute period during exposure to four controlled climatic conditions in an environmental chamber. These experimental conditions included a control (22°C and 50% humidity), hot-humid (37°C and 85% humidity), hot-dry (44°C and 15% humidity), and cold-dry (5°C and 80% humidity) exposures. All images were taken at a perpendicular angle from the skin surface at a distance of 0.45 mm, as measured using the camera's laser-guided range finder function. Baseline images were similarly taken during a preliminary rest period prior to each experimental exposure. This resulted in a total of 2,200 images collected from the left hand and left foot of the 25 participants. Following theoretical expectations, preliminary findings indicate peripheral digit temperatures predictably decrease during the cold-dry exposure, while the hot-dry and hot-humid exposures induce increases in digit temperatures. These preliminary results suggest that infrared thermography likely provides an expedient mechanism for accurately assessing peripheral skin temperatures in humans under different climatic conditions. Infrared thermography may thus have valuable applications for assessing thermoregulatory function in both clinical and research settings.
Carvedilol, an alternative for lowering liver stiffness in patients with cirrhosis and portal hypertension
(2024-05) Guriginjakunta, Niharika; Sankpal, Umesh; Heck, Amber J.
Liver cirrhosis, often associated with portal hypertension, presents a significant health burden globally. Carvedilol, a non-selective beta-blocker, has emerged as a promising therapeutic option for managing portal hypertension in patients with liver cirrhosis. This retrospective analysis assessed the effect of Carvedilol treatment on patients with liver cirrhosis and clinically suspected portal hypertension, focusing on its effects on liver function parameters, non-invasive fibrosis scores, and liver stiffness measurements. A total of 130 patients from the Liver Center of Texas were included in this retrospective analysis, comprising 65 patients in the treatment group receiving Carvedilol and 65 patients in the control group. Statistical analyses, including t-tests, were conducted to assess the differences between groups. Carvedilol treatment led to significant improvements in liver function parameters, including a reduction in AST levels, indicative of improved liver function. Non-invasive fibrosis scores, such as FIB-4, AGILE 3, AGILE 4, and APRI, showed notable improvements after Carvedilol treatment in the treatment group, suggesting a reduction in liver fibrosis and improved prognosis. Liver stiffness measurements using eKpa and CAP scores demonstrated significant reductions after Carvedilol treatment within the treatment group, indicating improved liver stiffness. The study suggests that Carvedilol is effective in managing portal hypertension in patients with liver cirrhosis. Further research is needed to confirm these findings in larger cohorts and evaluate the long-term efficacy, and safety of Carvedilol treatment. Additionally, addressing disparities in liver disease diagnosis and treatment is crucial for improving outcomes and reducing the burden of liver-related morbidity and mortality.
Comparative Patient Outcome Analysis Between Two Radiation Therapies for Head and Neck Cancers
(2023-05) Stein, Maggie J.; Ranjan, Amalendu P.; Basha, Riyaz; Neufeld, Sarah; Desai, Kajal