UTMB Health SHARED (Univ. of Texas Medical Branch at Galveston)
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Contribution of Secretion Systems to Macrophage Polarization and Cell Death During Burkholderia pseudomallei Infection
No full textBurkholderia pseudomallei is a Gram-negative environmental saprophyte and causative agent of melioidosis. As a facultative intracellular pathogen, B. pseudomallei uses secretion systems as primary virulence factors. The type 3 secretion system (T3SS) is used to escape the phagosome while the type 6 secretion system is responsible for cell-to-cell fusion and multinucleated giant cell (MNGC) formation. Both secretion systems are critical for virulence but the impact they have on the host response is uncharacterized. In this dissertation, we demonstrate the effect these secretion systems have on the immune response by evaluating macrophage polarization and cell death. Using two mutant strains, ∆bicA and ∆hcp1, as case studies, we demonstrate that there is a differential macrophage polarization and apoptosis response. Together, they represent host response elements that are manipulated by the bacteria in a secretion system dependent manner to promote replication within the host
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
Echoes of Trauma: The Relationship Between Poly-Victimization in Childhood and Health Outcomes
No full textThis study addressed the issue of poly-victimization during childhood and its impact on health outcomes. Bronfenbrenner’s social-ecological model and Lenz et al.’s theory of unpleasant symptoms were selected as the theoretical framework to explore this complex problem. The study’s global aim was to examine the relationship between poly-victimization in childhood and health outcomes, specifically sleep disturbance. The major research question is as follows: “What is the relationship between poly-victimization in childhood and health outcomes?” Primarily, the null hypotheses state, “There is no relationship between poly-victimization in childhood and health outcomes.” The study employed a secondary data analysis design, utilizing quantitative methodologies (such as ordinal logistic and multiple regression) to investigate the National Survey of Children’s Exposure to Violence Sets I, II, and III (2007–2014). The justification for this design is that secondary data analysis allowed leveraging existing datasets, potentially saving time, effort, and resources that would otherwise have been dedicated to primary data collection. This study demonstrated a significant positive association between poly-victimization and sleep disturbances—with participants who experienced multiple forms of victimization being 3.8 times more likely to suffer from sleep disturbances, leading to the rejection of the first null hypothesis. Contrary to expectations, psychological distress did not mediate this relationship but instead increased the strength of the association, resulting in the nonrejection of the second null hypothesis regarding mediation. The significance of this study lies in its potential to enhance understanding of the long-term ramifications of poly-victimization during childhood. This knowledge is crucial in developing effective interventions, counseling, and policies to improve health outcomes
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
NEUROBIOLOGY OF HUMAN AGENCY, NEUROPHILOSOPHY, AND NEUROLAW: COULD NEUROSCIENCE BECOME A COERCIVE FORCE IN THE FUTURE?
No full textThe dominance of the scientific method and the worldview it produces dominates all kinds of discourse. This dominance is increasing and continues to displace traditional ways of understanding phenomena. Unfortunately, the well-merited success of the scientific method has resulted in a displacement of many legitimate non-scientific ways of understanding. Since neuroscience is at the very cutting edge of technological endeavors, the ethical issues that arise due to a proliferation of neurotechnology need careful ethical analysis. As neuroscience develops, it continues to colonize other adjacent fields such as psychology and law. The reason is that the spectacular success of the scientific method has resulted in scientism. Uncritical reliance on neuroscience to solve social and moral problems can and will result in neuroscience becoming a tool of social control, coercion, and even totalitarianism. Since the scientific method is heavily reliant on reductionism, it tends to discount the phenomenological aspects of the human condition as they can not be subject to the kind of reduction that a rigorous application of the scientific methods requires. The human self is a product of mysterious phenomena only partially explainable by neuroscience. These mysterious phenomena that generate and perpetuate the human self are consciousness, free will, and memory. Since neuroscience can not explain the first two phenomena at a fundamental level, it is unfit to intervene in the human mind through access to the brain's physical structures. The brain-mind dichotomy remains an unsolved problem in philosophy and science. A reductionist approach to understanding the human condition will result in a scientistic understanding of the self, which degrades human personality and individuality to a mechanistic and robotic existence. Such attempts undermine the dignity of humans and endanger belief in the concept of free will. A logical result will be an overzealous manipulation of human behavior, undermining authenticity and exercise of moral agency. Governments, corporate giants, and other unscrupulous actors are quite likely to misuse neuroscience for morally questionable ends. Therefore, a critical reanalysis of the role and objectives of neuroscience is needed, and adequate checks and balances need to be instituted to protect human dignity and cognitive liberty
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
No full textSexual 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
HUMAN GENETIC VARIANTS IN ESSENTIAL SPLICING FACTORS AND THEIR IMPACT ON IMMUNE PATHOLOGY
No full textPre-mRNA splicing is critical for proper gene expression, and its dysregulation has been implicated in many human diseases including neurodegenerative disorders, cancers and autoimmune diseases. Splicing is a multi-step process executed by the spliceosome, which is composed of five small nuclear ribonucleoproteins (snRNPs) and hundreds of proteins that are generally referred to as splicing factors (SFs). Here we present two unique cases in which genetic variations in two essential SFs, DExD-box polypeptide 39B (DDX39B) and U2 small nuclear RNA auxiliary factor 1 (U2AF1), contribute to altered splicing of Forkhead box P3 (FOXP3) – an immunoregulatory gene critical for regulatory T (Treg) cell function and homeostasis. Mutations in FOXP3 cause immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome, and aberrant expression of FOXP3 has been associated with other diseases such as multiple sclerosis (MS) and non-small cell lung cancer (NSCLC). We previously described a single nucleotide polymorphism (SNP) in DDX39B, rs2523506, which is associated with increased risk of MS. The population homozygous for the risk allele had ~50% less DDX39B protein expression. Furthermore, we demonstrated that DDX39B expression is critical for proper splicing, expression and function of FOXP3. Here we describe the mechanism underlying the exquisite dependence of FOXP3 introns on DDX39B and the potential impact of rs2523506 in DDX39B on FOXP3 expression and autoimmunity. Additionally, we highlight splicing alterations in a patient with a complex immune phenotype and a de novo in-frame deletion in U2AF1. Moreover, we discuss the potential implications of these splicing alterations in the disease pathogenesis of the patient. These two examples of genetic variations in SFs showcase the importance of splicing and how its dysregulation can contribute to immune pathology
INVESTIGATING SEX DIFFERENCES IN THE TRANS-SYNAPTIC REGULATORS OF MESOLIMBIC DRIVEN PALATABLE FOOD INTAKE
No full textFood 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
Assessing Concurrent Use of Opioids and Benzodiazepines Using Urine Drug Test Results
No full textThe 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
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
No full textObjectives. 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