UTMB Health SHARED (Univ. of Texas Medical Branch at Galveston)
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Investigation of the interplay of yellow fever virus structural protein epitopes and genetic diversity
No full textYellow fever virus (YFV), a mosquito-borne flavivirus, is responsible for the disease yellow fever (YF), which is characterized by hemorrhagic fever and multiorgan failure. The disease is prevented by a live attenuated vaccine (LAV), strain 17D, that was derived from serial passage of the wild type (WT) strain Asibi in chicken tissue. The mechanism of attenuation of 17D is incompletely understood. This dissertation investigates the contribution of the envelope (E) protein in YFV attenuation through its role in genetic diversity, tissue tropism and recognition by WT and vaccine specific antibodies that bind E protein. Using infectious clones (i.c.) of both Asibi and 17D viruses, structural chimeras with swapped prME, E protein domain III (EDIII) and single site mutations at each of the residues that differ between WT and vaccine strain in structural proteins were generated. Using these chimeras, the determinants of focus morphology were mapped to residues E-52 and E-380. E-305 was shown to be critical to the increased multiplication kinetics of 17D virus compared to Asibi. Genotypic stability was investigated using Illumina deep sequencing methods and it was shown that the E protein contributes to the differences seen in the genotype of Asibi and 17D viruses, whereas M protein does not. Despite this, prME was not shown to contribute to YFV susceptibility to the antiviral Ribavirin. Tissue tropism was correlated with WT and vaccine epitopes as residues in EDI were critical to viscerotropism and WT mAb recognition and residues within EDIII were shown to be critical to neurotropism and vaccine mAb recognition. It was found that the attenuating processes of 17D were not comparable to the JEV SA14-14-2 LAV. This is unsurprising due to the empirical nature of legacy LAVs and suggests there are many mechanisms that could be employed to generate future flavivirus LAVs. Overall, the role of E in the attenuation of 17D seems to rely on several critical residues (E-52, E-170, E-305, E-325 and E-380) many of which contribute the net positive charge of the 17D virion
A Recombinant Vesicular Stomatitis Virus Expressing the Junin Virus Glycoprotein for Arenavirus Countermeasure Development
No full textArenaviruses are pathogens of biodefense importance due to their potential for aerosol transmission and mortality rates reaching 30%. Here, we evaluated the use of a recombinant vesicular stomatitis virus expressing the Junin virus glycoprotein (rVSVΔG-JUNVGP) for the development of countermeasures against arenaviruses. First, we evaluated rVSVΔG-JUNVGP as a vaccine against lethal Junin virus (JUNV) challenge in a guinea pig model. Currently, there are no JUNV vaccines licensed by the United States Food and Drug Administration (FDA) for at-risk individuals. We demonstrated that rVSVΔG-JUNVGP generated 100% protective efficacy against lethal JUNV challenge using a single vaccine injection. We also showed that rVSVΔG-JUNVGP induced robust, high avidity IgG antibody titers as well as detectable neutralizing antibodies. We next evaluated the use of rVSVΔG-JUNVGP as a tool for the detection of JUNV neutralizing antibodies. Conventional methodologies for the detection and quantification of JUNV neutralizing antibodies have several limitations, including the length of time necessary to obtain results (6-8 days) and the requirement of a high containment (BSL-3/4) laboratory. In this study, we showed that rVSVΔG-JUNVGP could overcome these limitations, detecting neutralizing antibodies with the same sensitivity as currently available methods, but more rapidly (within 48 hours) and without the need for a high containment laboratory. Lastly, for biodefense and public health purposes the development of a cross protective arenavirus vaccine may be an important long-term research objective. We therefore developed a panel of chimeric glycoproteins which simultaneously express immunogenic epitopes from multiple arenavirus pathogens. We demonstrated that all chimeric GPs were adequately processed intracellularly, packaged into a rVSVΔG-GFP virion from the plasma membrane, and capable of cellular entry. Our findings suggest that these chimeric GPs may be good candidates to move forward into a rVSV vaccine vector for evaluation of protective efficacy in-vivo. Overall, the findings in these studies demonstrate that a rVSV vector system can be utilized to successfully advance arenavirus and JUNV-specific countermeasure development
Examining Nurses' Moral Distress, Acts of Moral Courage, and Influence of Ethical Climate in Caring for COVID-19 Patients During the Pandemic
No full textThe 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
Illness Perceptions and Self-Efficacy in African American Women Diagnosed with Systemic Lupus Erythematosus
No full textBackground: There has been a growing body of research during the past decade which points to the disproportionately high rates of Systemic Lupus Erythematosus (SLE) morbidity and mortality among African American women in the United States. Of the research on health perceptions and behavioral modification, there has been limited research examining African American women’s beliefs and perceptions about their illness or views about their own self efficacy which is the ability to exercise some measure of control over their illness.
Objective: The purpose of this pilot study was to explore illness perceptions and self-efficacy in African American women diagnosed with Systemic Lupus Erythematosus utilizing the Modified Illness Perception Questionnaire-Revised and the Modified Self-Efficacy for Managing Chronic Disease Six-Item Scale and to examine whether relationships existed between these measurements and demographic characteristics.
Methods: This pilot study utilized a descriptive, exploratory research design.
Sample: The sample consisted of 40 African American women diagnosed with Systemic Lupus Erythematosus for at least six months or longer, 18 years of age or older and current residents of the United States.
Data Analysis: Data was analyzed using descriptive statistics (central tendency, interquartile ranges, variance, means, and standard deviation), correlational analysis (Pearson’s correlations, Logistic Regression and Multiple Regression) and tests of differences (t-tests, Mann-Whitney U). A statistical significance of ∂≤.05 was used for this research.
Conclusion: One of the central findings of this pilot study confirmed that African American women who expressed a greater sense of self-efficacy in responding to their SLE were found to have more positive perceptions about their ability to live with and cope in the face of this often-debilitating chronic illness. Higher self-efficacy was found to predict reduced negative illness perceptions for Emotions, Illness Coherence, Consequences and Personal Control. Although the exploratory design and limited sample size requires cautious generalization to the larger population of SLE patients, the confirmation of the positive role for self-efficacy supports treatment modalities that bolster individual competency in managing their conditions and provides the groundwork for comparative studies across ethnic groups and can more thoroughly examine the potential impact of self-efficacy on illness perceptions among a larger sample of African American women co-existing with Lupus
The Role of a Clinical Research Nurse: The Impact of Working Remotely
No full textClinical research nurses (CRNs) are an integral part of clinical trials and have a responsibility to care for research patients, collaborate within multidisciplinary teams, and manage protocol adherence. CRNs are often the hub of a multidisciplinary research team, and it is important to understand any changes to the clinical research nurse (CRN) role brought on by the shift to remote work. In the United States, billions of dollars are spent annually on thousands of active clinical trials; yet CRN role participation in clinical trials continues to be widely unknown (Cline & Showalter, 2020). Leveraging the Erlandson et al. (1993) Naturalistic Inquiry method, this study explores the perceptions and experiences of CRNs who transitioned to working remotely due to the Coronavirus disease of 2019 (COVID-19) pandemic and how the transition may have impacted their role. Eight participants were recruited using purposive and snowball sampling, who engaged in virtual data collection sessions between July and December 2022. Data were analyzed using the constant comparative method and thematic analysis. Category designation started with thirty-eight data themes that were categorized into twelve subcategories, that were further analyzed to produce three major categories. Study findings suggest that CRNs who transition to remote work navigated complex situations including role adaptation, and impact to clinical trials and the CRN psyche
Deletions in SARS-CoV-2 nsp6 enhance antagonism of type-I interferon signaling
No full textSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve and adapt long after it first emerged in 2019. As the causative agent of the coronavirus disease 2019 (COVID-19), a tremendous effort has been made to understand the molecular pathogenesis of SARS-CoV-2. Recent research has identified nonstructural protein 6 (nsp6) as a major contributor to SARS-CoV-2 replication through the formation of replication organelles, antagonism of interferon type I (IFN-I) responses, and NLRP3 inflammasome activation, a major factor of severe COVID-19. Here, I review the most recent published findings regarding the multiple roles of nsp6 in promoting SARS-CoV-2 replication and investigate further the effect of variant nsp6 mutations in molecular pathogenesis of SARS-CoV-2, specifically the antagonism of IFN-I pathways. I demonstrate that a mutant SARS-CoV-2 USA/WA1-2020 (WA1) containing a nsp6 mutation (ΔSGF-WA1) seen in the Alpha (B.1.1.7) and Omicron sublineages (BA.2, BA.4, BA.5) is less susceptible to IFN-α treatment in African green monkey kidney epithelial cells expressing the human co-factor TMPRSS2 (Vero E6-TMPRSS2) compared to full-length WA1. Nsp6 mutations ΔSGF and ΔLSG, a similar deletion found in BA.1 nsp6, augment the ability of nsp6 to block phosphorylation of STAT1 and STAT2 in vitro compared to WA1 nsp6, thereby suppressing the IFN-I signaling pathway. Furthermore, ΔSGF-WA1 infection of primary airway cultures secretes similar levels of infectious virus and viral RNA than WA1-infected cells but produces higher levels of intracellular viral RNA than WA1 and outcompetes parental WA1 in a competition experiment. Lastly, ΔSGF-WA1 infected mice have higher levels of viral RNA than WA1-infected mice and experience lower survival rates with a longer disease period. These data suggest that variants containing ΔSGF or ΔLSG mutations are more virulent and may cause more severe disease in COVID-19 patients
Differences between Men and Women in Risk Profile of commonly used metrics in Screening for Obstructive Sleep Apnea using NHANES data.
No full textObstructive Sleep Apnea (OSA) is a common chronic condition that is often underdiagnosed, especially in women due to differences in symptomology. OSA is diagnosed using polysomnography which is time intensive and impracticable as a screening method. Alternate methods for screening based on symptoms exist with varying sensitivities. This study used the National Health and Nutrition Examination Survey (NHANES) based on a nationally representative US sample (n=20,497) to test for associations between self-reported sleep apnea and risk factors, such as snoring, fatigue, hypertension, and obesity. Data was taken from the sleep questionnaire 2005-2008, along with BMI, blood pressure, and demographic data for 12,600 subjects at least 16 years old. After excluding those with missing data on the set of risk factors, the final sample was 8373. A main objective of the study was to see if there was a difference in risk profile between men and women. Multivariable model (using logistic regression) compared [snoring, observed apnea, somnolence, age, gender, hypertension, BMI, history of smoking, race/ethnicity, education, and annual household income] to self-reported sleep apnea. Results indicated that observed apnea had the highest risk of OSA (OR:7.435, 95% CI:5.698, 9.745) followed by obesity (OR:4.524, 95% CI:3.523, 5.849). Snoring, age, and annual household income had statistically differing risks between men and women
Integration of Homeostatic and Hedonic Brain Centers in the Regulation of Feeding Behaviors
No full textBinge-eating disorder (BED) and obesity are major public health problems that are associated with psychosocial distress, impairments in daily function, and life-threatening co-morbidities. Both diseases are driven by maladaptive feeding behaviors, namely pathological overconsumption of high-fat food. Pathological overconsumption of high-fat food is potentiated by aberrant homeostatic feeding behavior (i.e. titration of caloric intake), which typically associates with hypothalamic brain nuclei, specifically the paraventricular nucleus of the hypothalamus (PVN) which controls food intake to maintain body weight. Additionally, pathological overconsumption of high-fat food is exacerbated by the reinforcing properties of high-fat food that drive hedonic feeding, which is mediated by the nucleus accumbens (NAc) and the ventral tegmental area (VTA). Furthermore, dysfunction of homeostatic (PVN) and hedonic (NAc, VTA) feeding circuitry is hypothesized to underlie pathological overconsumption of high-fat food. This dissertation aimed to elucidate the interconnected mechanisms of homeostatic and hedonic signaling that may underlie pathological overconsumption of high-fat food, and identified the neuropeptide receptor NMUR2 and the neurotransmitter glutamate as novel regulators of binge-type eating, intake of high-fat food, and motivation for high-fat food
The Roles of Estate Planning and Social Support in Racial/Ethnic Disparities in Advance Care Planning and End-of-Life Care
No full textAdvance Care Planning (ACP)– completing advance directives, discussing end of
life care preferences, and assigning a durable power of attorney for healthcare – may be
associated with improvements in quality of end of life care and more specifically with
receiving care congruent with one’s wishes. Despite this, stark differences in completion
rates by Non-Hispanic Blacks and Hispanics compared to Non-Hispanic Whites are
observed. Much of the research on ACP has focused on describing associations between
sociodemographic factors and planning completion or planning completion and health care
received at the end of life (End-of-Life). However, few studies have proposed testable
hypotheses and investigated causal relationships for ACP completion, particularly among
Hispanic subgroups, and effects on end of life care received. This study uses nationally
representative data from the Health and Retirement Study to investigate explanatory causal
pathways in ACP completion and its effects on End-of-Life healthcare with a focus on
Hispanics. Results from this study will help providers better understand sociodemographic
factors that predispose patients to high risk for failing to plan for the end of life, health
systems identify target areas for system change, and policy makers understand the role
socioeconomic disparities play in end of life planning
Dogs as Healers: Explorations of How Dogs Promote Healing and Their Role as Healers
No full textDogs have been present in our lives for thousands of years. As our relationship with them has taken many forms and shifted over that time, one thing has remained: dogs have been a part of human healing in various ways. From being symbolic ancient healing deities to the therapy dogs and service dogs we think of today, dogs have alleviated our suffering in countless ways. However, we often don’t include dogs in our descriptions of who are healers. Rather, healers are mainly considered to be healthcare professionals such as doctors and nurses. In this thesis, I aim to understand what a healer is and who is a healer, thus expanding who can be a healer to dogs. To do this I explore dogs as healers in three ways. First, I examine the ways dogs have been healers throughout history. Second, I demonstrate the therapeutic benefits of interacting with dogs in clinical settings. Third, I use a practical approach to show how a limited understanding of a healer can inhibit care for people using an example of psychiatric service dogs for veterans. These three approaches show that using a broad and general understanding of healing and a healer does apply to dogs and that dogs are valuable contributors to promoting healing. This expanded understanding can then further the ability to alleviate human suffering by recognizing and appreciating dogs as healers