UTMB Health SHARED (Univ. of Texas Medical Branch at Galveston)
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Exploring the Relationship between Postpartum Anxiety and Ethnicity/Race: A Secondary Analysis of TriNetX Data
No full textThe problem of interest was the prevalence and impact of postpartum anxiety among women,
with a focus on the role of race and ethnicity. The theoretical framework was Intersectionality;
this framework allowed for an exploration of how race, ethnicity, maternal age, prenatal anxiety,
and prenatal depression diagnoses intersect to influence a Postpartum Anxiety diagnosis. This
study aimed to investigate and quantify differences in PA rates across the following racial and
ethnic groups: Black, White, Asian, American Indian or Alaska Native, Native Hawaiian or
Other, Hispanic, and Non-Hispanic and determined the association between race/ethnicity and
postpartum anxiety after adjustment for maternal age, prenatal anxiety, and prenatal
depression. The research questions were: What is the association between race/ethnicity and
postpartum anxiety, and does an association between race/ethnicity and postpartum anxiety
remain after adjusting for maternal age, prenatal anxiety, and prenatal depression diagnoses?
The hypothesis would reveal differences in the risk of PA diagnosis among racial and ethnic
groups, and the association remained between race/ethnicity after adjustment. The significance
of the study was to gain understanding and better target interventions and support mechanisms
for women from various racial and ethnic groups related to PA. The design for the study was a
secondary data analysis using the TriNetX database; the TriNetX database provided a
comprehensive view of the phenomenon of interest with the least amount of bias
A Two-Pronged Approach to Stemming the Opioid Epidemic: Preclinical Strategies for Substance Use Disorder Medications Development and Liquid Biopsy Detection of Inflammatory Pain
No full textThe U.S. is in the grips of a public health crisis driven by misuse of psychoactive drugs (e.g., prescription opioids, heroin). In consequence, this has generated a multitude of health issues, including overdoses, deaths and disability, as well as the increased incidence of opioid use disorder (OUD), a condition manifested by escalating physical and psychological impairments. While current FDA-approved OUD medications substantially improve the odds of recovery, the gravity of the opioid crisis demands investigation of novel, more efficacious treatment options. The prevalence of recreational opioid misuse is compounded by excessive prescribing of opioid analgesics. Despite regulatory efforts to mitigate poor prescribing practices, more than 17% of Americans possessed at least one opioid prescription in 2017 with the average number of total opioid prescriptions reaching 3.4 per person. Excess medications are often diverted to friends and family members for recreational use. Pain clinicians are in desperate need of a reliable methodology to quantify pain at the point-of-care to ensure appropriate dose titration required to mitigate the pain experience without overprescribing. The National Institutes of Health (NIH) have launched the Helping to End Addiction Long-Term (HEAL™) Initiative, a massive, multifaceted effort to combat the opioid epidemic. The two primary focus areas of the NIH HEAL™ Initiative Research Plan include “Improving Treatments for Opioid Misuse and Addition” and “Enhancing Pain Management” which contain explicit objectives, such as identifying new targets for OUD treatment and establishing acute and chronic pain signatures, respectively. The studies detailed in this dissertation align with the goals set forth by the HEAL™ Initiative. Our findings demonstrate that the serotonin (5-HT) 5-HT2C receptor (5-HT2CR) agonist lorcaserin robustly diminishes the reinforcing value of the prescription opioid oxycodone (OxyContin®) and does not possess abuse liability. We also have identified a list of genes associated with high drug relapse vulnerability that should be prioritized as candidates targets for development of SUD medications. Finally, we designed and implemented a proof-of-concept liquid biopsy approach to quantify inflammatory pain with the ultimate goal of enhancing prescribing practices at the point-of-care
Diet- and Probiotic-mediated Modulation of the Maternal Gut Microbiome Impacts Early-life Programming of Neurodevelopment and Behavioral Outcomes in Offspring
No full textNeurodevelopmental disorders are highly heritable; however, consensus is growing behind a two-hit model in which environmental exposures can promote disease in genetically predisposed individuals. Among environmental factors, those that impact the maternal gut microbiome during pregnancy are emerging as critical modulators of neurodevelopment and long-term behavioral outcomes in offspring. Specifically, disruption, or ‘dysbiosis,’ of the maternal gut microbiome during pregnancy is associated with adverse neurodevelopmental outcomes. Previously, we showed that maternal high-fat diet (MHFD) in mice induces gut dysbiosis, social dysfunction, and underlying synaptic plasticity deficits in male offspring (F1).
For this thesis, we investigated whether MHFD similarly induces dysbiosis in female offspring (F1), which we hypothesized would recapitulate the adverse in utero environment experienced by the F1 males and resulting social dysfunction in the F2 generation, even in the absence of a dietary challenge. Metataxonomic sequencing revealed a significant reduction in microbial richness among female F1 MHFD offspring, with a specific decrease in the abundance of short-chain fatty acid (SCFA)-producing taxa. Despite recovery of richness in the F2 generation, F2 social behavior remained impaired, implicating dysbiosis of the maternal gut microbiome in offspring social deficits. Post-weaning supplementation with probiotic Limosilactobacillus (L.) reuteri was sufficient to rescue F2 generation social deficits. Unexpectedly, L. reuteri exerted a differential impact on the microbiome of control versus MHFD-descendant F2 mice, revealing a relative instability of the MHFD lineage microbiome. These differences were particularly strong among females, and this previously unreported heightened responsiveness of the female gut microbiome to probiotic modulation presented an opportunity for intervention: probiotic targeting of the maternal gut microbiome during pregnancy to relieve offspring social dysfunction. Hence, we developed a 7-strain probiotic cocktail consisting of immunomodulatory taxa and administered it to control and HFD-fed dams during pregnancy and lactation. Antenatal targeting of the maternal gut microbiome was sufficient to restore neurotypical social behavior in the MHFD-descendant F1 generation.
Our results link maternal lineage HFD to instability of descendant microbial communities and maladaptive social behavior. Moreover, they highlight the potential for therapeutic targeting of the maternal gut microbiome to improve neurobehavioral outcomes in descendants
Electronic Strategies for Tailored Exercise to Prevent Falls (eSTEPS): A Case Study in Implementing Clinical Decision Support Tools to Improve Older Adult Health
No full textElectronic Strategies for Tailored Exercise to Prevent Falls (eSTEPS) is a research study
designed to reduce falls in community-based older adults through implementation of
electronic-health record clinical decision support tools. The parent site, Massachusetts
General Brigham, is conducting a randomized controlled trial to investigate if adults aged
65+ at high falls risk benefit from computerized alerts and evidence-based, exerciseoriented
order sets to reduce falls and falls-related injuries compared to usual care. The
University of Texas Medical Branch (UTMB) was selected as a replication site to further
test the clinical decision support tools in a pre-post implementation design. This report
outlines the strategies used by UTMB to implement the eSTEPS tools within its primary
care practices caring for high-risk older adults. Following the RE-AIM framework, we
report on the early reach, adoption, and implementation of (or adherence to) the
program (reserving effectiveness and maintenance reporting to later project phases).
The eSTEPS tools were implemented in April 2023. After excluding a two-month wash-in
v
period, we provide project outcomes from July 2023 through January 2024. In total, we
identified 3472 community-dwelling older adults at high falls risk within UTMB primary
care practices. The eSTEPS clinical alert fired for 3210 patients (92.5% of expected).
Clinicians used the evidence-based exercise-oriented order sets for 363 patients to
initiate referral for formal physical therapy or provide educational materials for a home
exercise program. Unfortunately, clinicians dismissed or deferred the clinical alert in 82%
of encounters for which it was fired. Preliminary data suggests the eSTEPS clinical
decision support tools promote accurate identification of older adults at high falls risk
within UTMB and effectively alert primary care clinicians to patients’ need for fallsreducing
interventions. We outline several steps necessary to improve project reach,
adoption, and adherence which will also enhance the project’s effectiveness to reduce
future falls and falls-related injuries. Our lessons learned can be applied across clinical
decision support tools intended to facilitate health assessment and promote evidencebased
interventions among community-based older adults
Investigation of Infectious Disease Associations with Cognitive Impairment using Electronic Medical Records
No full textAlthough infection-driven neurocognitive deterioration has been postulated for decades, definitive population-level evidence is scarce. We therefore undertook a multi-center electronic health record study to quantify the association between six clinically important infections—Herpes simplex virus (HSV), syphilis, Chlamydia trachomatis, coronavirus disease 2019 (COVID-19), cytomegalovirus (CMV), and human immunodeficiency virus (HIV)—and subsequent cognitive impairment. On June 12, 2025, we queried the global TriNetX network for encounters containing both diagnostic codes (ICD10-CM) and confirming laboratory results (LOINC) for each pathogen, constructing sex stratified cohorts of up to 1,932,669 exposed patients that maximized diagnostic certainty. A comparator cohort was derived from encounters coded Z00 (routine examination) after excluding any of the target infections by diagnosis or laboratory evidence totaling up to 131,5694 control patients. Baseline demographic characteristics were assessed using TriNetX’s Compare Outcomes module, which balanced age, race, and sex distributions through propensity score matching before survival analysis. Kaplan–Meier curves and matched measures of association were then used to estimate infection-specific hazard ratios for cognitive decline given a five-year follow-up window. Across pathogens, we observed heterogeneous, infection-dependent elevation in risk, indicating that certain infections may be nontrivial contributors to neurodegenerative trajectories. While there are inherent limitations to utilizing real-world data such as lack of biomarkers and neuropsychological testing as well as potential outcome misclassification and left censoring of comorbidities due to structural features of TriNetX, our results imply that renewed investment in sexually transmitted infection screening, treatment completion, and partner notification programs could be feasible targets to lessen the impact of cognitive impairment
Longitudinal Metabolic and Proteomic Changes Studied in an Experimental Model of Traumatic Brain Injury
No full textTraumatic brain injury (TBI) causes a series of complex molecular events resulting in long-term neurological deficits. Currently, it is not possible to predict which, if any, deficits might occur or when they might occur in an individual. Substantial challenges to the development of treatment strategies include the complexity and heterogeneity of the clinical presentation coupled with limited understanding of chronic disease progression. To address these issues, we hypothesize that longitudinal metabolomic and proteomic studies may reveal mechanistic details explaining secondary injury after TBI and the potential timing of the events. We have conducted these studies using complementary mass spectrometry approaches and determined significant molecular events at time points between 24 h and 1 year post TBI. In the acute period, the most significant events are increased utilization of glutamate oxidation, perturbations to glucose and one carbon metabolism, energy failure, impairment of antioxidant capacity, blood-brain barrier BBB breach and elevated glial acidic fibirillary protein (GFAP). GFAP levels remain elevated in the cortex and hippocampus at 3 months and return close to normal by 6 months. Surprisingly, GFAP increases in the cortex at 1 year for an unknown reason. By 2 weeks many of the metabolic perturbations have resolved. Potential interventions suggested from these metabolic studies include, nicotinamide riboside, lipoic acid, and DHAA. They would probably be most efficacious if given soon after the initial injury. ApoE spikes at 2 weeks along with Slc1a2, in both the cortex and hippocampus coinciding with normalization of cellular metabolism. Endogenous repair processes begin in the cortex at 2 weeks and continue at 3 months post injury. In the hippocampus, activation of Nrf2 pathways is observe at the 3 month time point and proteins related to neurogenesis/repair processes are found at the 6 month time point. Finally, at 1 year, in both the cortex and hippocampus we observe variable changes in glutamate transporter Slc1a2 and Gabra2 in the cortex, suggesting that the balance between glutamate and GABA is unresolved influx even 1 year post injury. At these later time points (> 2 weeks), interventions aimed at enhancing reparative processes like ApoE mimetics, or pharmacologic modulation of the Nrf2 pathway could be beneficial
ESTABLISHING VALIDITY AND RELIABILITY OF A SURVEY MEASURING INTENTION TO AID A PERSON WITH LIFE-THREATENING BLEEDING
No full textThe phenomenon of interest was intent to use bleeding control techniques (BCT). The study aims were to modify Miller and Pellegrino’s (2018) Intent to Aid for Lay Responders (I2A-CPR) Survey to reflect intent to use BCT, piloting the Intent to Aid for Bleeding Control Techniques (I2A-BCT) Survey. The guiding theoretical framework was the Integrated Behavior Model (IBM, Fishbein & Ajzen, 2010). The research questions were: (1) What are the internal consistency reliability and construct validity of the I2A-BCTs? and (2) What is the effect of the constructs on educators' intent to use BCT? The study was significant because it resulted in an instrument to measure educators’ intent to use BCT. The quantitative research design included survey and cross-sectional methodology. The sample (n = 32) were female, White, Texas educators teaching kindergarten through grade 12, who completed an online 5-point Likert scale I2A-BCTs. Results: Internal Consistency Reliability revealed good reliability; all 49 items loaded onto the four factors of the IBM: Attitude, Intention to Act, Personal Agency, and Perceived Norms. Chi-square/degrees of freedom demonstrated poor model fit but additional fit indices confirmed the good model fit. Correlational analysis revealed all four factors positively correlated with Intent to Use BCT. Conclusion. The IBM (Fishbein & Ajzen, 2010) provided a reliable and valid framework for examining how affect influenced intent to use BCT in educators. Future Research is needed with larger sample sizes to confirm the model structure
COMPASSION SUSTAINMENT: BURN NURSE RESILIENCE
No full textThis study investigates the interplay between psychological capital (PsyCap)—comprising hope, efficacy, resilience, and optimism—and the sustainment of compassion among burn nurses exposed to chronic patient suffering. Recognizing the critical role of compassion in healthcare, the research addresses the gap in understanding if positive adaptive cognitive mechanisms relate to the nurses’ ability to maintain compassion amidst emotionally taxing environments. Using a cross-sectional survey design, data from 37 burn nurses at two institutions in Galveston, Texas were analyzed. Compassion for others and psychological capital were captured using the validated instruments Compassionate Engagement and Action Scale (CEAS) and the Psychological Capital Questionnaire (PCQ). The findings revealed significant positive correlations between PsyCap dimensions and various constructs of compassion, with several moderate to strong associations. While exposure to patient suffering was hypothesized to moderate these relationships, the relationship varied by institution, thus suggesting a contextual difference in how suffering exposure affects compassion and psychological capital. These results underscore the potential of PsyCap as a protective framework for enhancing nurse resilience and sustaining compassion in high-stress environments. The study highlights implications for clinical practice, including the design of interventions to bolster psychological resources and support nurses in delivering compassionate care, thereby contributing to improved outcomes for both patients and caregivers
INFLAMMATION INDUCED CYTOSINE DEAMINATION DAMAGE IN CANCER ETIOLOGY
No full textCancer is a major health challenge worldwide, and inflammation is thought to be an important factor in cancer etiology. The mutational landscape of human cancer is dominated by cytosine to thymine transition mutations, and the primary mechanism for these mutations is the deamination of cytosine and cytosine analogs to uracil and the corresponding uracil analogs. During replication, uracil and uracil analogs codes as thymine, leading to the aforementioned transition mutation. However, inflammation is known to cause a characteristic guanine to thymine transversion mutation due to the oxidation of guanine to 8-oxoguanine that mispairs with adenine during replication. Herein lies the unsolved conundrum- if inflammation causes guanine to thymine transversion mutations, why is the prevalent mutation observed a cytosine to thymine transition mutation?
In my dissertation, I first report a novel method to measure cytosine adducts through enzymatic release by mispair selective glycosylases and analysis by GC/MS/MS. I then propose and model a hypothesis to elucidate how partially redundant and potentially competing DNA repair pathways could be a critical link between oxidative damage and the widely observed cytosine to thymine transition mutations through oligonucleotide studies. Lastly, I extrapolate the method described earlier to Next Generation Sequencing (NGS) experiments and provide the corresponding evidence to support the previous two studies through NGS data.
The methods described here will be valuable for understanding DNA damage and repair pathways involved in genetic mutations that drive human cancer, and the applications of these results are vast- ranging from advancements to laboratory procedures to mechanism-based biomarkers for early cancer detection
Novel Roles of the Aryl Hydrocarbon Receptor in Normal Physiology and Epigenetic Reprogramming
No full textThe Aryl hydrocarbon Receptor (AhR) is a ubiquitously expressed, evolutionarily conserved, ligand activated, cytosolic transcription factor belonging to the basic Helix-loop-helix Per-ARNT-Sim superfamily of proteins. AhR has classically been associated with environmental toxicology owing to the fact it mediates the toxic effects of halogenated aromatic hydrocarbons and environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD exposure in laboratory animals is linked to carcinogenicity, hepatic steatosis, and a lethal wasting syndrome. In recent years, AhR knockout and antagonism have been reported to confer resistance to western diet induced obesity as well as reversing diet induced obesity. Together, these observations suggest a direct role for AhR regulating normal metabolic homeostasis and implicate AhR as a potential therapeutic target for obesity. However, much of the foundational knowledge of AhR biology is based on the use of exogenous, toxic AhR agonists. Through the use of a hepatocyte specific, inducible AhR knockout mouse model, the studies presented in this dissertation seek to address the gap in knowledge of the normal, physiologic functions of AhR in the absence of man-made toxicants.
In addition to revealing the physiologic functions of AhR, this work also investigates a non-canonical AhR signaling pathway mediated by a novel protein complex consisting of AhR, Kruppel-like factor 6 (KLF6) and carbamoyl phosphate synthetase 1 (CPS1). This complex binds a unique DNA motif termed the Non-Consensus Xenobiotic Response Element (NC-XRE). CPS recruitment results in homocitrullination of linker histone H1 lysine 34 (H1K34hcit). Homocitrullination, a novel epigenetic mark, was observed only in response to exogenous AhR agonists and is absent upon treatment with endogenous AhR ligands such as cinnabarinic acid. Results presented here demonstrate AhR-CPS1 dependent H1K34hcit is associated specifically with Pai-1 and Padi2 promoters and is required for transcriptional regulation. We posit that H1K34hcit is responsible for increasing mobility of histone H1, altering the local chromatin structure, thereby favoring transcription of NC-XRE containing genes. This represents a novel paradigm for AhR in the epigenetic regulation of gene expression. The studies presented in this dissertation shed light on both the subtle, physiologic activity of AhR and the AhR mediated epigenetics of TCDD toxicity