Published ETD Collection

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Influence of Natural Disasters on the Long-term Incidence of Depressive Symptoms, Cognitive Impairment, and Limitations in Activities of Daily Living Among Older Mexican Americans
(2023-08) Hufton, Amie; Prochaska, John (joprocha@utmb.edu)
Objectives. To estimate the risk factors, including exposure to natural disasters, associated with incident depressive symptoms, cognitive impairment, and limitations in activities of daily living among older Mexican Americans. Methods. I performed multivariable logistic regression of the H-EPESE from Wave 5 (2004-2005) to Wave 7 (2010-2011) to examine the incidence of three health outcomes. The analyses were restricted to participants that did not have indicators of 1) depressive symptoms (n=725), 2) cognitive impairment (n=774) and 3) limitations in activities of daily living (n=715) at Wave 5; natural disaster exposure was defined as residing in a county that received public assistance funds from the Federal Emergency Management Agency in 2006-2008. Results. Natural disaster exposure was not a significant risk factor in either of the three incident health outcomes. Self-report of heart attack increased the odds of all three health outcomes. Older age was associated with cognitive impairment and limitations in activities of daily living. Financial strain increased the odds of depressive symptoms and cognitive impairment. Conclusions. Natural disaster exposure is not associated with the incidence of depressive symptoms, cognitive impairment or limitations in activities of daily living between Waves 5 and 7. Understanding risk factors, including the role of natural disaster exposure, associated with the long-term health of aging Hispanic populations is essential, especially considering the increasing representation of this minority group in the US population.
Normalizing the Abnormal: Self-Identified Traumatic Events and Critical Care Nurses, A Focused Ethnography
(2024-05) LaGrone, Judson Paul; Leger, J. Michael (jmleger@utmb.edu); Martin, D. Cheyenne; Cupit, Tammy; Farroni, Jeff; Hale, Gina
According to The National Institute for Occupational Safety and Health (2022), 20 million healthcare workers in the United States (U.S.) are at risk for symptoms of mental unhealthiness directly related to their work environment and experiences. Despite nurses reporting higher levels of burnout and other adverse effects within their work environment, approximately two-thirds of nurses indicate they are not receiving supportive resources for mental health, which is known to impact physical health (Berlin et al., 2023). The pandemic has shed light on pre-existing conditions for nurses, such as the workplace culture and understaffing, leading to unmanageable patient loads, which all minimize nurses' mental health (Bowie, 2022). Critical care nurses (CCNs) encounter singular and often repetitive traumatic events (TEs) within the work environment, which lead to adverse effects such as anxiety, depression, post-traumatic stress disorder, secondary traumatic stress disorder, burnout, compassion fatigue, moral distress, substance use, and suicidal behaviors. A TE is described as an extreme event causing an individual’s ability to cope to be threatened, resulting in unusual and strong cognitive, emotional, or behavioral reactions (Kleim et al., 2015). A limited number of studies have directly addressed the experiences of self-identified TEs among CCNs in the clinical work environment. This study aims to describe the CCN’s TE, explore potential psychological impacts on the CCN, explore work culture impacts on the CCN’s response, and examine resources offered to the CCN. A focused ethnography (Roper and Shapira, 2000) methodology was used for the study and was guided by the research question, “What are CCNs’ experiences and responses to a self-identified traumatic event(s) in the emergency department or intensive-care unit settings that caused them distress?” Purposive and snowball sampling was used for recruitment. CCNs (n=11) representing various regions in the U.S. participated in semi-structured interviews. Study data included demographic data, transcribed interviews, field notes, and methodological journals. Collected data was analyzed using the constant comparative method (Glaser, 1998; Glaser and Strauss, 1967) until redundancy and data saturation occurred. The study utilized Beck’s (1993) criteria to demonstrate scientific rigor. Data analysis revealed four themes of normalizing the abnormal, suffering in silence, badge of honor, and resilience: we are CCNs.
RESPIRATORY PARAMETERS, PULMONARY REHABILITATION and SURVIVAL in COVID-19 PATIENTS
(2024-05) Micheals, Khamron 1992-; Rojas, José (jdrojas@utmb.edu); Al Snih, Soham (soalsnih@utmb.edu); Walsh, Brian K. (bkwalsh@utmb.edu); Golovko, George (gegolovk@utmb.edu); Tucker, Carole A. (cartucke@utmb.edu); Gardenhire, Douglas (dgardenhire@gsu.edu)
Background: Coronavirus disease 2019 (COVID-19) is a highly infectious viral illness, which targets patient’s respiratory system. Objectives: To (1) determine whether respiratory mechanics, oxygenation impairment, sociodemographics, and multimorbidity of mechanically ventilated COVID-19 subjects are associated with survival; (2) determine the factors associated with physical function status after completing six weeks of pulmonary rehabilitation (PR) of COVID-19 subjects with persisting pulmonary symptoms; and (3) investigate the impact of socioeconomic (SES) disparities on participation in PR and morbidity of Long COVID patients. Design: Retrospective analysis using the electronic health records. Participants: Adults ≥ 18 years, with positive COVID-19 diagnosis that were mechanically ventilated (n = 415). Adults with positive COVID-19 diagnosis with persisting dyspnea that completed PR (n = 68). Adults with ICD-10 diagnosis for Long COVID within the TriNetX database (n = 67,019). Measures: Sociodemographics, comorbid conditions, respiratory mechanics, University of California – San Diego Shortness of Breath Questionnaire score, 6-minute walking distance, anxiety, depression, post-traumatic stress disorder, survival and morbidity. Analysis: Descriptive statistics were performed to assess the sample characteristics. Generalized estimating equation models was used to assess survival. Multivariate regression was used to assess improvement in physical function. Kaplan curve analysis was performed to assess participation of PR and morbidity. Results: Being younger, female, and Non-Hispanic White were associated with survival of mechanically ventilated COVID-19 patients. Most Long COVID patients had improved physical function following PR. Conclusions: Sociodemographic factors were significantly associated with survival. As pulmonary dynamic compliance increased, survival increased in mechanically ventilated COVID-19 subjects. Non-Hispanic Blacks had lower odds of physical function improvement after completing PR than Non-Hispanic Whites. Long COVID patients with SES disparities were more likely to have lasting morbidity issues.
Investigating the Molecular Mechanism of Ribosome Recycling
(May 2024) Seely, Savannah Marie 1996-; Gagnon, Matthieu (magagnon@utmb.edu); Yin, Yuhui (ywyin@utmb.edu); Smith, Thomas (thosmith@utmb.edu); Leiman, Petr (pgleiman@utmb.edu); Chopra, Ashok (achopra@utmb.edu); Tsai, Francis (ftsai@bcm.edu)
In all living cells, the ribosome translates the genetic information carried by messenger RNAs (mRNAs) into proteins. The process of ribosome recycling, a key step during protein synthesis that ensures ribosomal subunits remain available for new rounds of translation, has been largely overlooked. Despite being essential to the survival of the cell, several mechanistic aspects of ribosome recycling remain unclear. Aminoglycosides are a class of antibiotics that bind to ribosomal RNA and exert pleiotropic effects on ribosome function, including recycling inhibition. Amikacin, the semisynthetic derivative of kanamycin, is commonly used for treating severe infections with multidrug-resistant, aerobic Gram-negative bacteria. Amikacin carries the 4-amino-2-hydroxy butyrate (AHB) moiety at the N1 amino group of the central 2-deoxystreptamine (2-DOS) ring, which may confer amikacin a unique ribosome inhibition profile. During stress conditions such as antibiotic exposure, ribosomes stall on messenger RNAs, leading to inhibition of protein synthesis. To remobilize ribosomes, bacteria use rescue factors such as HflXr, that catalyzes the dissociation of translationally inactive ribosomes into individual subunits. Here we use in vitro fast kinetics combined with X-ray crystallography and cryo-EM to dissect the mechanisms of ribosome inhibition by amikacin and the rescue of stalled ribosome through HflXr-mediated recycling. Amikacin interferes with tRNA translocation, release factor-mediated peptidyl-tRNA hydrolysis, and ribosome recycling, traits attributed to the additional interactions amikacin makes with the decoding center. The binding site in the large ribosomal subunit proximal to the 3’-end of tRNA in the peptidyl (P) site lays the groundwork for rational design of amikacin derivatives with improved antibacterial properties. Using time-resolved cryo-EM, we show that within the 70S ribosome, HflXr displaces helix H69 of the 50S subunit and induces long-range movements of the platform domain of the 30S subunit, disrupting inter-subunit bridges B2b, B2c, B4, B7a, and B7b. Our findings unveil a unique ribosome recycling strategy by HflXr which is distinct from that mediated by RRF and EF-G. The resemblance between HflXr and housekeeping HflX suggests that the alternative ribosome recycling mechanism reported is universal in the prokaryotic kingdom.
Searching for their Path: Understanding Parents of Children with Emotional Disturbance
(May 2024) Nighswander, Michelle 1969-; Blair, Patricia (pablair@utmb.edu); Prochaska, John; Leonard, Bruce; Leger, J. Michael; Rounds, Linda
Background: Children with Emotional Disturbance (ED) have unpredictable reactions and behaviors, which cause significant problems for themselves, their families and society (Zionts et al., 2016). The child’s reactions are highly disproportionate, chronic and frequent (Gage, 2013). These children have significant risks related to their ED, including school drop-out, incarceration, unemployment and substance abuse (Lipscomb et al., 2018). Purpose: The purpose of this study was to explore participants’ experiences related to raising a child with ED, participants’ response to situations related to their child’s ED, and how a child with ED impacted the family. Method: This study explored the parenting experiences of mothers of children with ED, utilizing Naturalistic Inquiry as described by Lincoln and Guba (1985) and Erlandson et al. (1993). After IRB approval, eight mothers were recruited nationally through social media. Results: Three overarching constructs emerged in the study. The first construct, “concerns and suspicions,” was the evolution of mothers’ concerns, rationalizations, escalations, decision and eventual confirmation that their child was “different.” “Actions and adaptations” depicted the actions used to manage their child with ED, along with actions for self-care and siblings’ care. “Altered families and advice for others” described how every family member was impacted by the child with ED and participants’ advice on how to ease the difficulties for other families. Study findings suggested needed changes to nursing practice, education and policy.
Assessment of Reflective Teaching Practice in Undergraduate Nursing Faculty
(May 2024) Jacob, Priya; O'keefe, Mary E. (meokeefe@UTMB.EDU); Juarez, Adrian (axjuarez@UTMB.EDU); Nguyen, Hoang T. (hnguyen@UTMB.EDU); Campo-Engelstein, Lisa (licampoe@UTMB.EDU); Jammer, Veronica (veronica.jammer@sjcd.edu)
The goal of the study was to assess levels of Reflective Teaching Practice employed by undergraduate nursing faculty and teach measures to increase utilization in undergraduate nursing program. This proposed Pilot was conducted using a pre- and post-intervention design with a convenience sample of participants. Using this design, the study compared the level of engagement in self-reflection score in Reflective Teaching Practice (RTP) pre- and post-Strategic Reflective Training Session (SRTS) in undergraduate nursing faculty, as measured by the Self-Reflection and Insight Scale (SRIS); and determine the relationship between engagement in self-reflection score pre and post SRTS as measured by the SRIS, and years of teaching experience as recorded on the Demographic Data Sheet. A paired t-test was conducted to calculate the difference in level of engagement pre- and post-SRTS; and a one-way ANOVA was conducted to determine the relationship between engagement of self-reflection score pre-SRTS, post- SRTS, and years of teaching experience. Based on the data analysis, there was no statistically significant difference in overall engagement in self-reflection score pre- and post-SRTS, and there was no statistically significant difference between the years of experience and pre- and post-SRTS scores.
Searching for their Path: Understanding Parents of Children with Emotional Disturbance
(May 2024) Nighswander, Michelle 1969-; Blair, Patricia (pablair@utmb.edu); Prochaska, John; Leonard, Bruce; Leger, J. Michael; Rounds, Linda
Background: Children with Emotional Disturbance (ED) have unpredictable reactions and behaviors, which cause significant problems for themselves, their families and society (Zionts et al., 2016). The child’s reactions are highly disproportionate, chronic and frequent (Gage, 2013). These children have significant risks related to their ED, including school drop-out, incarceration, unemployment and substance abuse (Lipscomb et al., 2018). Purpose: The purpose of this study was to explore participants’ experiences related to raising a child with ED, participants’ response to situations related to their child’s ED, and how a child with ED impacted the family. Method: This study explored the parenting experiences of mothers of children with ED, utilizing Naturalistic Inquiry as described by Lincoln and Guba (1985) and Erlandson et al. (1993). After IRB approval, eight mothers were recruited nationally through social media. Results: Three overarching constructs emerged in the study. The first construct, “concerns and suspicions,” was the evolution of mothers’ concerns, rationalizations, escalations, decision and eventual confirmation that their child was “different.” “Actions and adaptations” depicted the actions used to manage their child with ED, along with actions for self-care and siblings’ care. “Altered families and advice for others” described how every family member was impacted by the child with ED and participants’ advice on how to ease the difficulties for other families. Study findings suggested needed changes to nursing practice, education and policy.
Assessing Concurrent Use of Opioids and Benzodiazepines Using Urine Drug Test Results
(December 2022) Taha, Shaden 1989-; Yong-Fang Kuo
The purpose of this dissertation was to assess concurrent use of benzodiazepines and opioids, using laboratory results from urine toxicology records. The opioid crisis is an ongoing public health issue that has spanned over two decades. Drug overdose death is now the leading cause of accidental deaths among American adults. Patients who take benzodiazepines and opioids concurrently are at even greater risk of overdose than those taking an opioid alone. Prominent agencies including the Centers for Disease Control and Prevention, Food and Drug Administration and the Centers for Medicare and Medicaid Services strongly recommend against co-prescribing opioids and benzodiazepines when possible, and the use of urine drug testing to mitigate patient risks through monitoring and early intervention. Although there have been studies on co-prescribing rates using prescription data, there is little evidence on the rates of patient drug use using UDT data. This dissertation used large, population-based administrative data to address the following research gaps using patient urine drug test (UDT) results: 1) examine trends in concurrent opioid and benzodiazepine use among adult patients and assess whether there was a shift from prescribed to illicit or non-prescribed drug use; 2) determine patient characteristics associated with aberrant UDT results—concurrent use, illicit drug use or non-prescribed use; 3) assess provider response to concurrent use-positive UDT. This research gives an understanding of recent trends and associations with concurrent opioid and benzodiazepine use by patients and may inform more targeted public health practice.
Ehrlichia chaffeensis Activates Notch Signaling Through SLiM Mimicry to Inhibit Apoptosis
(May 2022) Patterson, LaNisha LaTice 05/07/1989-; Jere Mcbride; Thomas Smith; Andres Oberhauser; Gracie Vargas; Joya Chandra; Spyros Artavanis-Tsakonas
Ehrlichia chaffeensis is a small, obligately intracellular gram-negative bacterium, and the etiological agent of human monocytotropic ehrlichiosis (HME), an emerging, life threatening tick-borne zoonosis. E. chaffeensis infects mononuclear phagocytes and has evolved molecular strategies to reprogram the host cell involving secreted effectors that interact directly with the host cell targets. Recently, we have shown E. chaffeensis evasion of innate defenses of the macrophage involve activation of Wnt, Hedeghog and Notch signaling pathways. Interestingly, the E. chaffeensis tandem repeat effector, TRP120, has been shown to interact with host proteins important for activation and regulation of conserved signaling pathways including Wnt, Notch and Sonic Hedgehog. In this study, we investigated the molecular interactions and functional implications of Notch activation during E. chaffeensis infection. The objective of this research project is to identify the SLiM ligand mimetic in E. chaffeensis TRP120 and the functional implications of TRP120 Notch activation. Two aims were originally proposed to investigate this hypothesis. Aim 1 was to elucidate the molecular interactions required for TRP120 Notch activation. Aim 2 was to investigate the role of E. chaffeensis Notch stabilization of XIAP and inhibition of caspase activation. Based on the evidence collected during my research, I have concluded that a TRP120- TR Notch SLiM memetic motif directly binds Notch-1 at a region containing the LBD to activate Notch signaling. TRP120 Notch activation results in an anti-apoptotic program involving inhibitor of apoptosis proteins (IAPs) that inhibits caspase activation for intracellular survival. We demonstrate sequence homology between TRP120 and Notch ligands and determined that the TRP120-TR shares significant identity with known Notch ligands. We determined direct interactions between TRP120 and NECD recombinant protein containing ligand interaction domain, EGFs 1-13. We further defined the TRP120-TR domain as being capable of Notch activation and have defined the TRP120 Notch SLiM memetic motif required for Notch activation. Furthermore, we determined a direct correlation between Notch activation and inhibition of apoptosis linked to an increase in XIAP expression during E. chaffeensis infection. Increased XIAP levels correlated with increased NICD levels during E. chaffeensis infection and after TRP120 Notch ligand mimetic peptide treatment. Additionally, increased XIAP expression was consistent with increased pro-caspase levels. siRNA knockdown or inhibition of XIAP with small molecule inhibitor significantly increased apoptosis and Caspase-3, -7 and -9 levels and decreased ehrlichial load. This investigation reveals a mechanism whereby E. chaffeensis repurposes Notch signaling to stabilize XIAP and inhibit apoptosis. Understanding the molecular basis of Ehrlichia-Notch ligand mimicry is important for understanding the survival strategies of intracellular pathogenesis. Defining such interactions may lead to the development of novel therapeutics that target host-pathogen protein-protein interactions. The proposed study is highly significant in revealing a molecular mechanism whereby obligately intracellular pathogens, with small genomes and limited protein effectors, have evolved moonlighting proteins and molecular mimicry to rewire conserved signaling pathways and cellular functions to ensure persistent infection and survival. The identification of a short linear motif found within a non-canonical Notch ligand gives more insight into the underlying molecular mechanisms of aberrant Notch activation and may therefore lead to therapeutic approaches for diseases by which constitutively activated Notch signaling leads to disease onset and progression. Understanding Notch activation during E. chaffeensis infection will allow for the development of agents targeting critical steps of Notch signaling to inhibit infection and survival in the macrophage.
The Impact of Acculturation on Quality of Life in African American Women Living with A Lung or Colorectal Cancer Diagnosis
(August 2022) Garner, Danya Tymon
The purpose of the proposed pilot study was to explore potential relationships between acculturation, selected demographic characteristics and perceived quality of life in African American women who have been diagnosed with and received treatment for colorectal or lung cancer. There is limited research examining potential cultural and demographic factors related to the ability to cope and maintain quality of life. A descriptive, exploratory research design was used for this study and utilized three surveys to gather data including the African American Acculturation Scale-Revised World Health Organization Quality of Life Instrument – BREF, and a Demographic Data Form. A total of 15 African American women who had been diagnosed with lung or colorectal cancer during the past five years were recruited for this pilot study. Data were analyzed using descriptive statistics including measures of central tendency, interquartile ranges, variance, and standard deviation as well as tests of differences, Mann Whitney U, and linear regressions. A statistical significance of α < .05 was the standard used for this research. Results of the research study provided baseline data about the impact of American women with colorectal or lung cancer . Published results will assist in filling the existing gap in research literature.
Elucidating Mechanisms of Immunity to Nipah Virus Infection through Generation of Attenuated Viruses and a Single-Cycle Vectored Vaccine
(December 2021) Foster, Stephanie Leigh
Nipah virus (NiV) is an emerging paramyxovirus that has caused outbreaks with high case-fatality rates in South and Southeast Asia. Mechanisms of NiV virulence are poorly understood, and there is no licensed vaccine nor treatment. Accessory proteins produced from the NiV P gene through co-transcriptional gene editing (V and W) inhibit multiple molecules in the type-I interferon (IFN-I) induction and response pathways to modulate the host innate immune response to NiV infection. Previously, ferrets infected with a recombinant NiV (rNiV) lacking V survived an otherwise lethal NiV challenge via an unknown mechanism. Mutation of the V gene of the related canine distemper virus prevented binding of V protein to melanoma differentiation-associated protein 5 (MDA5) and attenuated virulence in an otherwise lethal ferret model. The NiV V-MDA5 binding site and the effects of blocking this interaction on virulence were previously unknown. The work described here identified amino acid I414 in NiV V as a critical residue for binding to MDA5 through co-immunoprecipitation/western blot and IFN-β dual luciferase reporter assays in a plasmid overexpression system. Subsequently, rNiV lacking the ability to bind to MDA5 and signal transducer and activator of transcription 1 (STAT1) were recovered, characterized in cell culture with and without IFN-I pretreatment, and used in an experimental infection model in ferrets. Interestingly, 25% of ferrets infected with the rNiV lacking V survived challenge with a higher virus dose than in previous studies, while 75% of ferrets infected with a rNiV lacking the ability to bind to MDA5 and STAT1 survived. These experiments identified MDA5 and STAT1 together as important targets for NiV virulence. Additionally, previous NiV vaccine candidates have shown efficacy against NiV challenge in a variety of animal models, but no virus-vectored vaccines have been tested for efficacy shortly prior to challenge, as in an outbreak scenario. Therefore, a vesicular stomatitis virus-vectored NiV vaccine was rescued and tested in African green monkeys. Animals were protected from lethal challenge with NiV when the vaccine was given seven or three days prior. The vaccine is non-replicative and yet works rapidly in a single dose with no adjuvants. Combined, the experiments described here will advance understanding of NiV virulence and development of effective vaccines against this deadly infection.
Aging Skeletal Muscle Plasticity in Exercise and Injury
(May 2021) Brightwell, Camille R.
Sarcopenia—progressive loss of muscle mass and strength—diminishes quality of life and longevity. In addition to progressive atrophy, older adults exhibit impaired regeneration after muscular injury. Activity of muscle stem cells, termed satellite cells, is dysregulated with aging which impairs skeletal muscle remodeling and limits plasticity of aged muscle. Aim 1 (Chapter 2) of this dissertation seeks to clarify the debated requirement of satellite cells for overload-induced hypertrophy in aging muscle via a common surgical overload model, with the original hypothesis that while aging satellite cells contribute to overload-induced hypertrophy to mitigate sarcopenia, growth can occur in the absence of satellite cells via expansion of the myonuclear domain. In light of Aim 1 results demonstrating no overload-induced hypertrophy in aging skeletal muscle with surgical overload, Aim 2 (Chapter 3) examines the efficacy of a novel and translatable murine resistance exercise model to elicit satellite cell expansion with myonuclear accretion and hypertrophy in aging skeletal muscle, with the hypothesis that this novel exercise model would result in expansion of the satellite cell pool along with hypertrophy not observed in old mice with the surgical overload model. Indeed, PoWeR (Progressive Weighted wheel Running) elicited hypertrophy in old mice, likely supported by a robust angiogenic response in hind limb muscles. Lastly, Aim 3 (Chapter 4) examines the efficacy of a novel NNMT inhibitor to enhance regeneration of aging skeletal muscle after injury by enhancement of satellite cell proliferation and fusion to myofibers, confirming the hypothesis that NNMT inhibition would rescue age-related deficits in satellite cell activity to promote superior regeneration of muscular injury of old mice.
Investigation of ARNT isoform-specific regulation of AHR signaling
(May 2021) Bourner, Luke
The aryl hydrocarbon receptor nuclear translocator (ARNT) is alternatively spliced into two distinct isoforms, isoform 1 and 3. Although ARNT is found to be critical in immunity, xenobiotic, and hypoxic response, ARNT isoform-specific function has yet to be investigated. We previously demonstrated that primary lymphocytes express both of these isoforms, however malignant T cells overexpress ARNT isoform 1 to promote cell viability. In this study, we find that the ARNT isoforms have opposing roles in aryl hydrocarbon receptor (AHR) signaling, as ARNT isoform 1 suppresses AHR activity, whereas ARNT isoform 3 is needed for AHR target-gene transcription. Furthermore, to explore this suppressive role, we investigated a unique modification specific only to ARNT isoform 1 – phosphorylation of serine 77 (S77). We determined that phosphorylation at S77 is initiated following AHR activation and is critical for the augmentation of AHR-target gene transcription. These results further highlight the importance of investigating ARNT isoform-specific function and reveal an essential role of ARNT isoform 1 phosphorylation in AHR signaling. Collectively, these findings increase our understanding of a complex regulatory mechanism by which ARNT regulates AHR signaling, further aiding in the comprehension of their roles in immunity and supporting the potential of targeting ARNT alternative splicing as a means of therapeutic intervention in hematological diseases and malignancies.
A novel GC-MS/MS assay for the measurement of 2-hg enantiomers and the utility of 2-hg enantiomer levels as a biomarker for IDH mutant gliomas
(May 2021) Strain, Shinji Kenneth
The isocitrate dehydrogenase (IDH) gene has recently been identified to be mutated in gliomas, a malignant brain tumor. Mutant IDH (IDHmut) produces the oncometabolite, (R)-2-hydroxyglutarate (R-2-hg), resulting in a significant increase of intracellular concentrations above physiological levels. However, a lack of correlation between circulating 2-hg levels and IDH status has been observed. This is likely due to the lack of discrimination from the enantiomer of R-2-hg and (S)-2-hydroxyglutarate (S-2-hg). S-2-hg is also normally made in the body but can increase to levels comparable to R-2-hg during hypoxic and acidic conditions. Thus, it is important to differentiate between R-2-hg and S-2-hg to determine the utility of R-2-hg as a biomarker. Furthermore, the current mass spectrometry (MS) methods available for the separation and detection are lacking. Current assays use laborious methods that can result in interconversion of enantiomers during sample preparation, and since low-resolution mass spectrometry instruments have been utilized, incorrect characterization of 2-hg MS data has occurred. A novel chiral gas chromatography-tandem mass spectrometry (GC-MS/MS) assay was developed which improves upon current methods. The assay utilizes a simplified ethyl acetate extraction, separates 2-hg enantiomers using a chiral column which avoids racemization, and quantifies 2-hg enantiomers using stable-isotope dilution MS. Using 2-hg isotopologues, unique EI fragmentation pathways for both 2-hg and the 2-hg lactone have also been described resulting in the ability to simultaneously detect both 2-hg and 2-hg lactone enantiomers. The assay was then validated and serum 2-hg levels from healthy patients were measured, establishing a new, comprehensive reference range for normal levels of each enantiomer. Differences in basal levels of 2-hg enantiomers were observed between races but not sex. Finally, serum levels of 2hg enantiomers were measured in patients with and without IDHmut gliomas. An increase in R-2hg levels was observed for a number of patients with growing IDHmut gliomas, however, not all patients with IDHmut gliomas had an increase in R-2-hg levels. Increased S-2-hg levels were also observed in patients who received prior chemotherapy/radiotherapy. Further work is needed to fully understand circulating 2-hg enantiomer biology, but the work presented herein takes a significant first step in providing the tools and framework for understanding the clinical utility of R-2-hg as a biomarker for IDHmut gliomas.
Novel Biomarkers within Extracellular Vesicles for the Identification of Traumatic Brain Injury
(May 2024) Tang, Zifeng Tony 1989-; Szczesny, Bartosz; Motamedi, Massoud; Micci, Maria; Zhao, Yingxin; Bossmann, Stefan
Traumatic brain injury (TBI) is defined by the National Institute of Neurological Disorders and Stroke (NINDS) as “…external physical forces cause damage to the brain, whether from impact, penetrating objects, blast waves or rapid movement of the brain within the skull”. According to the most recent CDC data, there were roughly 214,000 TBI-related hospitalizations and 70,000 TBI-related deaths in 2021. The current diagnosis of TBI includes a neurological exam such as Glasgow Coma Scale (GCS) and imaging tests (CT, MRI). However, these modalities have several limitations, including inter-rater reliability, inconsistencies in diagnosis, and lack of predictive prognosis, all of which highlights the complex pathophysiology of this disease process. Thus, there is an urgent need for identification of novel methods for an early detection and quantitative monitoring of TBI. In this project, we investigated extracellular vesicles (EVs) in blood plasma as a potential source of novel TBI biomarkers. Key characteristics of EVs, including the protection of the packaged cargo that reflects processes occurring in the cell of origin and their ability to cross the blood-brain-barrier (BBB), make them a highly valuable source of biomarkers. We subjected 10–12-week-old C57BL/6J male mice to moderate/severe TBI using the pre-clinical, closed head, weight drop model followed by EVs isolation from blood plasma at multiple time points post injury. We detected time-dependent qualitative and quantitative changes in the biophysical properties of EVs. Furthermore, we discovered TBI induced changes in specific EVs subpopulations of microglia/macrophage CD11b+ and astrocyte ACSA-2+ vesicles post-injury. These temporal dynamics of EVs are also reflected in both mitochondrial DNA content, nuclear DNA content, and brain-derived cellular markers NFL, GFAP, and Iba1. Additionally, we combined a global mass spectrometry proteomics approach with biostatistical analysis and computational Graph Neural Network (GNN)-based modeling to discover a panel of potential novel biomarkers for the detection and severity of TBI. Lastly, we confirmed the dynamic release of mtDNA and its fragments in EVs from neurons using an in-vitro TBI model and EVs derived from glucose oxidase stressed retinal pigment epithelial cells, respectively. Together, our findings indicate that a combination of DNA quantity, SAA, and CFD proteins in EVs may be used as diagnostic tools for the rapid, accurate assessment of TBI detection and its sequelae.
A Naturalistic Inquiry of the Experiences of Women Diagnosed with Gestational Diabetes
(December 2023) Mandia, Diana; Dr. Adrian Juarez (axjuarez@utmb.edu); Dr. Carolyn Phillips (Retired); Dr. Patricia Blair; Dr. Monique Pappadis; Dr. Sandra Lee
Gestational diabetes, hyperglycemia that develops in pregnant women with no prior history of diabetes, affects 2% to 10% of all pregnancies in the United States (Centers for Disease Control and Prevention [CDC], 2022). About 50% of women with GDM go on to develop T2DM, and babies of women diagnosed with GDM also are at increased risk of developing T2DM later in life (CDC, 2022). Effective management of GDM requires women to change their health behaviors related to diet, exercise, and medication adherence. Although some studies have examined the experiences of women who have been diagnosed with GDM in other parts of the world, there is a need for research that explores the experiences of women with GDM living in the United States. The current study utilized Naturalistic Inquiry [NI] (Erlandson et al., 1993; Lincoln & Guba, 1985) to explore and describe the experiences of women diagnosed with gestational diabetes [GDM] in a previous pregnancy and were living in the United States. Data collection took place in the form of one-on-one interviews via Zoom Video Conference with women diagnosed with GDM in a previous pregnancy currently living in the United States. Study data consisted of interview data and participants’ demographic data. Interview data was analyzed using Erlandson et al.’s (1993) interpretation of Lincoln and Guba’s (1985) approach to inductive data analysis. Data analysis revealed three major categories: 1) Finding Out About the Gestational Diabetes Diagnosis, 2) Mastering GDM, and 3) Life After GDM. The implications of the study’s findings pertain to nurses and other healthcare providers who help care for pregnant women diagnosed with GDM. Women with GDM need more information about GDM risk factors, how to incorporate GDM recommendations into their daily lives, mental health resources, and whether having had GDM posed long-term risks for themselves and their children.
Nurse Educators' Perspectives and Experiences with Clinical Judgment
(December 2023) Rosen, Chelsey Lynn 1992-; Richard, Patricia (plrichar@utmb.edu); Rounds, Linda (lrounds@utmb.edu); Martin, Darlene (damartin@utmb.edu); Prochaska, John (joprocha@utmb.edu); Bosenbark, Margaret (margaret.bosenbark@bswhealth.org)
Sound clinical judgment (CJ) is an essential skill every nurse needs to care for individuals competently and safely. Over the last two decades, nursing education has struggled to sufficiently prepare and develop students’ CJ, despite various educational and curricular changes. This study utilized a Naturalistic Inquiry approach to explore prelicensure nurse educators’ perceptions and experiences with teaching and evaluating nursing students’ CJ to gain essential insight to educators’ perceptions of this education deficit. Eight prelicensure nurse educators participated in this study, recruited through the memberships of the National League for Nursing (NLN). Data saturation was evident after six participants. Four main categories emerged from the data: Making Sense of Clinical Judgment, Efforts to Foster Clinical Judgment in the Classroom and Clinical Setting, Perceived Challenges for Nurse Educators Related to Clinical Judgment, and The Next Generation National Council Licensure Examination (NGN) Impact. The findings indicate nursing education needs to agree on a definition and utilization of a CJ model to help teach. The findings also indicate creating an active learning environment, using simulation, and educators actively posing questions to students are strategies used to foster CJ in the clinical and classroom settings. The data from this study also reveals prelicensure nurse educators’ perceived challenges to teaching and evaluating students’ CJ and their perceptions on the new changes to licensure examination. The findings from this study support and add to the accelerating body of literature on nursing CJ and lay the groundwork for future research on fostering nursing students’ CJ
Location, Location, Location: Assessing the Role of Context in Moderating the Relationship Between Childhood Adversity and Mental Health Burden
(December 2023) Nguyen, Amanda 1994-; Peek, Kristen M. (mkpeek@utmb.edu); Pappadis, Monique R.; Prochaska, John; Mehta, Neil; Al Snih, Soham; Buschmann, Robert
Adverse childhood experiences (ACEs) have profound mental health implications throughout the life course. While literature has focused on individual risk factors for ACEs and their burden on health, there are social and physical environmental contextual factors outside the individual that have been overlooked in studies of childhood adversity. This dissertation sought to understand how environmental context (social and physical environment) moderates the relationship between prior ACE exposure and mental health by using the 2015 Behavioral Risk Factor Surveillance System (BRFSS) and County Health Rankings. By using the BRFSS and the County Health Rankings, this dissertation assessed ACE burden and mental health as well as examined participants’ context at the county level. The goals of this dissertation are to: (1) explore how to define context using social and physical contextual variables, (2) evaluate if context can act as an effect modifier in the relationship between childhood adversity on mental health, and (3) assess if there are racial/ethnic differences on how context moderates ACE burden on mental health. The results of this proposal shed light on how certain aspects of context can buffer the burden of ACEs on mental health, and these results can be used as evidence for allocation of funds to help alleviate the ACE burden at the county level.
Essays on the impact of housing insecurity and other socioeconomic factors on health-related outcomes among Medicare beneficiaries during the Great Recession
(December 2023) Hernandez, Monica; Mehta, Neil (nemehta@utmb.edu)
While previous recessions have informed much of our modern-day fiscal policy, they have informed less of relevant housing or healthcare policies focused on preventing or mitigating the effects of housing insecurity during economic crises. In this dissertation, I drew from nationally representative Health and Retirement Study (HRS) data to evaluate the role of housing insecurity on healthcare and health outcomes among Medicare beneficiaries ages 65+ during the Great Recession (2008-2012). In Paper 1, I assessed associations between housing insecurity and foregone medication due to cost. Findings indicated a greater odds of foregone medication among individuals experiencing onset versus persistent housing insecurity, suggesting that unexpected acute economic shocks leave households with little time to adapt and lead to forced trade-offs in basic needs. Guided by the disparities literature, in Paper 2, I examined racial differences in foregone medication among non-Hispanic White (NHW) and Black (NHB) beneficiaries during the 2008 Recession peak to evaluate the extent to which housing insecurity and predisposing, need-based and enabling factors within Andersen’s healthcare utilization model explained the Black-White racial difference. Findings indicated statistically significant associations between race and foregone medication that were explained with the addition of non-housing wealth. These findings suggest wealth was a stronger driver of racial disparities in foregone medication than housing insecurity during the Recession. Guided by stress-health frameworks, in Paper 3, I examined the association of housing insecurity with depressive symptoms among Medicare beneficiaries during the Recession and further assessed the extent to which Andersen’s factors explained this relationship. Findings indicated that baseline housing insecurity had a positive yet insignificant effect on average depressive symptoms during 2008-2012, however, this relationship became negative and significant with the addition of baseline wealth and tenure status, suggesting the strong confounding effect of these variables on the role of housing insecurity on depression. In summary, the three papers fill important gaps in our understanding of the health effects of the Great Recession, including the extent to which housing insecurity was associated with foregone medication due to cost and depression as well as how patterns in forgone medication differed by race and other socioeconomic characteristics.
Examining Nurses' Moral Distress, Acts of Moral Courage, and Influence of Ethical Climate in Caring for COVID-19 Patients During the Pandemic
(May 2024) Willcott, Emily; Martin, Darlene (damartin@utmb.edu)
The problem of interest was the nurses in the United States (U.S.) and their moral actions taken in the care of COVID-19 patients. Since March 2020, the U.S. has recorded over 103 million COVID-19 cases and over 1.1 million COVID-19 deaths (CDC, 2023). Healthcare workers comprised nearly 1.2 million of the cases and 2,500 of the deaths (CDC, 2023). Nurses’ moral stances in response to pandemic pressures varied. Nurses were seen acting morally courageous by sacrificing themselves for the care of their patients, and yet a handful of nurses abused their licenses and made unethical decisions by falsifying vaccine cards. Nurses experienced unprecedented stress, leading to experiences with moral distress, but there is limited literature regarding nurses’ moral responses to moral distress during their care of COVID-19 patients. Examining the hospital environment incited by the pandemic as well as see how nurses responded to moral distress in the hospitals was imperative.

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