UTMB Health SHARED (Univ. of Texas Medical Branch at Galveston)
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THE ROAD LESS TAKEN: CHARACTERIZING THE TRIGEMINAL NERVE ROUTE OF NEUROINVASION BY RESPIRATORY SARS-COV-2
No full textCOVID-19, while primarily recognized as a respiratory disease, also presents with a wide range of neurological symptoms, including seizures, anxiety, depression, amnesia, attention deficits, and alterations in consciousness. Although the olfactory nerve is widely accepted as the primary route of neuroinvasion by which the etiological agent SARS-CoV-2 invades the brain, the trigeminal nerve may serve as an additional, yet often overlooked, neuroinvasive route. We initially conducted a pilot study using AC70 human ACE2 transgenic mice, which were subjected to intranasal inoculation of SARS-CoV-2, to investigate the olfactory nerve route of neuroinvasion. We incidentally found the trigeminal ganglion is an additional extrapulmonary, peripheral nervous site of viral infection akin to the well-known olfactory epithelium. To explore the possibility of the trigeminal nerve as a route of neuroinvasion by SARS-CoV-2, we then conducted a more detailed study using the same mouse model to characterize the route and found the trigeminal ganglion is an early and highly efficient site of viral replication which then rapidly spread throughout the brain and appearing to primarily target neurons. Despite the extensive spread of virus within the brain, we did not consistently observe significant tissue pathology, such as inflammatory infiltration, glial activation, or apoptotic cell deaths, which are typically associated with neuroinvasive viral infections. However, our findings indicated a significant induction of inflammatory cytokines, suggesting an active immune response. Additionally, we observed alterations in the expression levels of several genes related to neuronal function, including those involved in the dopamine neurotransmitter pathway, synaptic function, and markers of neuronal damage, when compared to control mice. These findings suggest that the trigeminal nerve may act as a complementary route to the olfactory nerve for SARS-CoV-2 neuroinvasion, leading to a distinct neuropathological profile. Our study provides valuable insights into the potential mechanisms of coronavirus-induced neuropathogenesis and underscores the importance of further research into the neurological impacts of COVID-19
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
Quantitative Analysis of Hardiness within Night Shift Nurses: A Survey-Based Study
No full textThe research examined the relationship between fixed night shift nurses and their level of hardiness, utilizing the Dispositional Resilience Scale (DRS-15). The study focused on nurses in acute care settings, categorized into four groups based on years of night shift experience. Employing a cross-sectional quantitative design, data was collected via an online survey including demographic questions and the DRS-15. The theoretical framework was the society-to-cells resilience theory, integrating multiple levels of analysis to understand human development. Statistical analyses included descriptive statistics, Pearson's r correlation, and one-way ANOVA. Key findings
revealed that nurses working fixed night shifts for 7-9 years demonstrated the highest levels of hardiness on the DRS-15 scale. Furthermore, the analysis of the three components of hardiness, commitment, control, and challenge, showed nurses scored highest within the variable of commitment. The study contributes to the understanding of hardiness in night shift nurses, potentially informing strategies for nurse retention, improving work environments, and developing targeted interventions to enhance nurses' resilience
Moral Imperatives in Physician Writing: A Counterethic
No full textMy dissertation addresses ethically problematic uses of patients in the published writings of physicians. Narrative medicine conceptualized as clinical practice fuels the reading and publishing of physician narratives and their public dissemination. Ethical lapses and harms to patients can result from the conflation of care, research, and writing. However, ethical treatment in the scholarly literature has focused narrowly on consent, privacy, and confidentiality. Comparing the instrumentalization of patients to the treatment of colonial subjects, I undertake the first ethical study of the physician writings of postcolonial theorist Frantz Fanon. For this interdisciplinary research, I use conceptual and analytical methods from philosophy, literature, and social medicine. Using as primary sources ethical norms and standards for publication, Fanon's physician writing and theoretical and didactic works in literature and medicine, I propose to re-evaluate assumptions behind physician writing and epistemic practices of medicine. I examine the epistemological and methodological premises underlying the publication of physician writing to reveal unchallenged modes of knowledge production. I perform a close reading of Fanon’s literary treatment of patients to identify his ethical intents and commitments. My analysis of different ways of knowing, thinking, and narrating the patient informs the elaboration of an argument about the ethical permissibility of physician writing that departs from the prevailing normative framings of research and clinical care. Through the elaboration of a counterethic for physician writing, I generate new knowledge about physician responsibilities and the ethical and social ramifications of this practice
Dysregulated TFH cell and germinal center activation in mice with severe Orientia tsutsugamushi infection
No full textScrub typhus is a severely understudied tropical disease caused by Orientia tsutsugamushi. It is endemic in, but not limited to, the Asia-Pacific region, with about one million cases reported every year. Its high case fatality rates and impact during WWII and the Vietnam War justify vaccine development; however, little is known regarding B cell responses or B/T cell crosstalk during infection. Our transcriptomic analyses of mouse spleens at a severe disease stage have revealed widespread alterations in B cell function. Our central hypothesis is that impaired expression of B cell-regulating cytokines and transcriptional factors accounts for dysregulated B cell activation during severe scrub typhus. This thesis contains the first study of cellular/molecular mechanisms underlying B cell dysfunction during infection in mouse models. It will help elucidate disease pathogenesis and the observation of “poor immune memory” known to be associated with scrub typhus
Of Cyborgs and Chimeras: Our Future With Emerging Technologies
No full textThis dissertation is an interdisciplinary exploration of the sociological, ethical, and philosophical implications of emerging technologies, with a special focus on biomedical engineering, more specifically neuro-interventions. I explore various technologies from algorithms, AI, and augmented/virtual reality to service robotics and neuroprosthetics in terms of research and application. On both these levels, the distinction between therapeutic and nontherapeutic (cosmetic) uses of technologies is discussed in detail, which situates my discussion in existing scholarship on human enhancement and bioengineering (e.g., gene editing). Combining an overview of the history of cybernetics with explorations of consciousness theories and personhood (particularly in the context of brain-computer interfaces) allows me to build a larger philosophical argument about the relationship of humankind and enhancement technologies: human exceptionalism is a barrier to all flourishing and a solarpunk-inspired approach to neuroethics may be the solution. My claim is that the human condition needs to be expanded and upgraded into the sentient condition, which, by promoting a compassionate and respectful approach to all sentient beings and their potential, encourages a reconciliation among humans, nature, and technology and leads to a better and sustainable future
Role of Mincle in Immune Responses to Orientia tsutsugamushi infection
No full textScrub typhus is a major public health concern for more than one billion people living in or travelling to endemic countries. The causative agent of scrub typhus, Orientia tsutsugamushi, is an obligate intracellular bacterium transmitted via bite of the Leptotrombidium mite (chigger). O. tsutsugamushi replicates in endothelial cells and macrophages (MF) and initial symptoms of infection are nonspecific, including cough, headache, and malaise. The lung is a target organ during infection and if treatment is delayed mild disease can progress to lethal pulmonary, cardiac, and neurologic syndromes. However, little is known regarding immune recognition of the bacterium and transitional mechanisms from mild to severe disease.
The first objective of this work defined the contribution of Mincle, a C-type lectin receptor (CLR), in innate immunity to O. tsutsugamushi. Following lethal infection in C57BL/6 mice, pulmonary differential expression analysis revealed Mincle (Clec4e) among the top 5 greatest up-regulated genes, accompanied with CLR signaling partners (FcRg), and type 1-skewing cytokines/chemokines. To validate a role of Mincle in scrub typhus, we exposed murine bone marrow-derived macrophages (MF) to live or inactivated O. tsutsugamushi. We found that while heat-killed bacteria stimulated transitory Mincle expression, live bacteria generated a sustained Mincle response. Notably, infection had limited impact on other tested CLRs or TLRs. Sustained proinflammatory gene expression in MF was also induced by live, but not inactivated, bacteria; infected Mincle-/- MF significantly reduced proinflammatory responses compared with WT cells.
The second objective was to examine the contribution of multiple CLRs to inflammation via inhibiting the adaptor protein necessary for CLR signal transduction (Syk). Infected/Syk-inhibited MF displayed significant reductions in Mincle, Clec5a, and proinflammatory/type-1 transcripts when compared with infected-but-untreated cells. Notably, the abrogated inflammatory response observed in infected Syk-inhibited cells was more pronounced than that seen in Mincle-/- cells, implicating multiple CLRs in sensing the bacterium. Surprisingly, MF displayed Syk-dependent, antiviral-like responses during infection.
Together, we show that CLRs play an important role in sensing O. tsutsugamushi and generating proinflammatory immune responses during infection. My work has shed light on novel aspects of the innate response to O. tsutsugamushi and uncovered potential drivers of inflammation during infection
Float Nurses’ Association with Nurse Sensitive Indicators: A Cross-Sectional Study
No full textFloating is a common nurse staffing strategy, yet its effects on nurse-sensitive indicators (NSIs) remain largely unexplored. The study aimed to evaluate the effects of two distinct forms of floating: nurses from dedicated float pools and unit-based nurses temporarily assigned to other units. Using a cross-sectional, secondary data analysis methodology, the study focused on float nurses’ relationships with four NSIs: Falls, Hospital-Acquired Pressure Injuries (HAPI), Central Line-Associated Bloodstream Infections (CLABSI), and Catheter-Associated Urinary Tract Infections (CAUTI). Data was collected from 25 critical care and medical/surgical units across three hospitals from April 2023 to April 2024, utilizing the National Database for Nursing Quality Indicators (NDNQI) and existing nurse staffing records. A logistic regression analysis revealed two key findings: float pool nurses were associated with a decreased risk of HAPI (OR 0.96, 95% CI 0.92-0.99) and CLABSI (OR 0.93, 95% CI 0.88-0.99). In contrast, increased frequency of unit-based floating correlated with a higher risk of HAPI. While float pool nurses were not associated with elevated NSI risks, frequent floating of unit-based nurses may negatively impact patient outcomes. Recommendations include standardized tracking of floating practices and future longitudinal studies to refine staffing policies
From Driven Clinical Nurses to Influential Nurse Leaders: A Phenomenological Study of Millennial Nurse Leaders' Experiences in Acute Care Settings
No full textMillennials are the largest generational cohort in the United States workforce. This group brings a unique essence to the workplace, as the first generation who were raised as digital natives. Their socio-historical experiences have shaped millennials’ values, beliefs, and perceptions. Millennial-aged nurses are moving into nursing leadership roles as nurses of the baby boomer generation retire. The COVID-19 pandemic accelerated advancements in healthcare, but also heightened a fragile nursing profession, where nurses’ and nurse leaders’ resilience were fully tested. The Review of Literature examined millennials pre- and post-COVID-19 pandemic and millennial nurse managers’ experiences; however, no studies were found that examined all roles of millennial nurse leaders’ experiences in the acute care setting. This study utilized a qualitative, phenomenological methodology, guided by Karl Manheim’s Theory of Generations theoretical framework. The study’s research question was: What are the lived experiences of millennial nurse leaders in acute care settings? The study’s findings indicated millennial nurse leaders’ experiences centered around professional development, sense of belonging, and growth as a leader. The study’s findings have implications for nursing practice, education, and policy
The Role of Socioeconomic Status and Race/Ethnicity in Orthotopic Liver Transplantation Outcomes in U.S. Adults Ages 50 and Older, 2002-2012
No full textOrthotopic liver transplantation (OLT) currently represents a life-saving procedure used to extend and improve the quality of life for those with End-Stage Liver Disease (ESLD). However, this procedure, the gold standard of treatment for ESLD, is not readily accessible to all populations. Racial and socioeconomic disparities exist throughout the organ transplantation and specifically orthotopic liver transplantation system today. Research has shown that these social disparities impact the development and progression of any given disease, including ESLD. This study uses data from adults 50 years and older from 2002 – 2012 who underwent an orthotopic liver transplant procedure recorded in the Scientific Registry of Transplant Recipients (SRTR) and performs logistic regression analyses informed by two specific aims. To satisfy the overall objective of this investigation, which is to better understand the relationship between socioeconomic status (SES) and OLT outcomes, as well as the mechanisms behind race/ethnicity and SES disparities regarding OLT outcomes, two specific aims will be addressed. First, to assess the extent to which lower SES is associated with patient survival through the first-year post-OLT and examine a possible mediating effect that waitlist time has on the association in OLT occurring between 2002-2012. And second, to examine possible moderating effects race/ethnicity may have on the relationship between SES and the OLT outcome of patient survival during the first-year post-transplant occurring between 2002-2012 and comparing outcomes of both Hispanic and non-Hispanic Black patients to non-Hispanic White patients. The study was unique in that it utilized the first decade of OLT transplantation outcomes since the MELD score was implemented, as well as looked at one-year post-transplant Hispanic outcomes. Aim 1 results were mixed in that while it supported a connection between waitlist time, socioeconomic status, and death within one-year post-transplant, the waitlist was not significant as a mediator. Aim 2 results showed that there was a moderating effect of race/ethnicity on socioeconomic status and death within one-year post-transplant. It also supported the hypothesis that Hispanic patients have better first-year post-transplant outcomes than non-Hispanic Blacks. This study furthers our understanding of the problem of inequality and disparities as they relate to the interconnectedness of SES and race regarding liver allocation and immediate survival one-year post-OLT