UTMB Health SHARED (Univ. of Texas Medical Branch at Galveston)
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Congenital Chagas Murine Model Development and Nanovaccine Efficacy Against Maternal-fetal Trypanosoma cruzi Pathogenesis
No full textMaternal infection with Trypanosoma cruzi (Tc) parasite can lead to the vertical transmission from mother to fetus known as congenital Chagas’ disease (cCD). The objective was to develop a murine model of cCD to test the efficacy of a DNA nanovaccine developed by our laboratory. In this dissertation, we demonstrate that Tc infection in female mice delayed the initiation of pregnancy, reduced fertility rate, and resulted in vertical transmission of the parasite to the offspring. Pups born to infected dams showed lower survival rates, decreased birth weights, and impaired growth rates. Moreover, these pups exhibited significantly elevated levels of inflammation, necrosis, and fibrosis in their cardiac and brain tissues. A higher initial dose of the parasite had more detrimental effects on both fertility rates and the health of the pups, regardless of whether the dams were acutely or chronically infected. We have also established that Tc infection triggered delayed and insufficient activation of T cells, resulting in low levels of effector molecules that are needed for controlling the spread and replication of the parasite in both pregnant and non-pregnant dams. The nanovaccine showed enhanced immunity in pregnant mice compared to non-pregnant mice. Following challenge infection, the vaccine effectively enhanced the splenic differentiation, maturation and polyfunctional activation of CD4+ and CD8+ effector/effector memory and central memory subsets, with increased production of interferon gamma, perforin and granzyme B that exhibit cytolytic activities against the infected cells. Further, nanovaccine immunized pregnant mice exhibited effective control of the parasite burden in maternal tissues and inflammatory infiltrate, necrosis, and fibrosis in maternal (heart, skeletal muscle) and fetal placentas. Consequently, maternal fertility rate and pregnancy outcomes were improved in vaccinated infected mice. Together, we demonstrate that nanovaccine offers a valid strategy to elicit protective immunity against Tc infection during pregnancy, leading to improved control of maternal Tc infection and favorable fetal outcomes
Unraveling the Effects of Nicotine-Derived Nitrosamine Ketone (NNK) on Healthy and Neurodegenerative Brain via Intravital Imaging and Multiscale Ex Vivo Imaging Approaches.
No full textCigarette Smoke (CS) continues to be a leading cause for decline in quality of life and deaths globally. While the link to poor health and early death has been accepted for decades, it is increasingly recognized smoking may contribute to neurological disease. Epidemiologically, CS has been associated with neuroinflammation and neurological disorders, including Alzheimer’s disease, stroke, and multiple sclerosis. Nicotine-derived nitrosamine ketone (NNK) is a nicotine metabolite produced within the tobacco plant from combustion and metabolic breakdown of nicotine. Extensive cancer literature has established NNK as an important component of CS resulting in DNA mutation and ability to bind and activate nicotinic acetylcholine receptors. However, little is known about specific in vivo effects of NNK on the blood brain barrier (BBB)or microglial immune cells of the brain as they relate to the vasculature. To investigate microglial and vascular responses to intranasal NNK in vivo, we combined the use of a transgenic mouse (CX3CR-1GFP) with intravital neuroimaging. We show that NNK given intranasally over acute (4-7days) and chronic (12 weeks) exposures, leads to disruption of the BBB and heterogenous
microglia activation. Machine learning algorithm was employed to segment microglial soma from processes, and analyses performed to evaluate morphometry and associations with vasculature. In vivo microglia activation was found e heterogeneous; with ameboid activated microglia localized to the vasculature. An increase in vessel-associated microglia compared to PBS controls was found. Pronounced effect of NNK on vasculature included vasoconstriction, vasodilation, and microhemorrhage. In chronic treatment, these effects were sustained and, in some cases, exacerbated. Both neuronal and DNA damage was found; interestingly the later confined to cells other than microglia indicating microglia may be acting in a productive phagocytic function
(quantified in vivo). The transgenic 3xTg-AD (Alzheimer’s disease) mouse model was used to investigate the vascular and microglia effects of NNK during ongoing disease progression, and marked increase in vascular events, similar to CX3CR-1 GFP were found. Lipofuscin autofluorescence was observed in intravital imaging for both PBS and NNK-treated groups and showed overall increase in lipofuscin deposition with NNK treatment over 4 days vs. PBS. Vessel
leakage was also increased with NNK. Large-scale microscopy of optically cleared mouse lungs revealed an increase of internal red blood cell deposition in NNK-treated groups and distorted alveolar structure that was not observed in PBS-treated groups. Taken together, this work suggests an immunomodulatory effect of NNK marked by highly vessel-localized microglia activity and vascular dysfunction that can produce long-term pathophysiology that could contribute to or exacerbate ongoing or developing disease processes. This work lays the groundwork for studies examining the potential role of other components in
cigarettes or e-cigs as it relates to neurological disorders as well as studies examining the multiorgan effects (lung-brain) of NNK
Searching for their Path: Understanding Parents of Children with Emotional Disturbance
No full textBackground: 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
DNA-Launched Vaccines for Emerging and Re-emerging Viral Pathogens
No full textGiven the large number and increasing frequency of viral outbreaks around the globe, there is a need to address the availability, consistency, and production of vaccines. Although there are approved vaccines for some of these diseases there are still issues that face the implementation of these vaccines is susceptible populations in endemic areas. To address these issues, it was necessary to develop and implement an efficacious, and cost-effective vaccine platform that will elicit strong immune responses when compared to currently approved vaccines. We have developed a rapidly adaptable DNA platform to which previously established, licensed vaccines can be converted, or new vaccines can be developed around. Our DNA-launched vaccine platforms provide a foundation for the additional development of live-attenuated vaccines (LAV) and novel subunit vaccines. For DNA-launched LAVs, the in vitro launched viral particles behave consistently with previous studies. With direct in vivo launch of LAVs from this DNA platform, we are able to achieve similar immune responses in immune deficient mice and superior immune responses in immune-competent mice as traditional methods of LAV vaccination. The in vivo launch of our DNA-based LAVs had a better safety profile than direct injection of in vitro rescued viral particles rescued from the same plasmid. The in vivo electroporation of DNA based LAVs elicits an immune response that can protect mice from a high-dose lethal challenge. We also developed a DNA-launched replicon-based subunit vaccine that can elicit strong immune responses after vaccination and is able to completely prevent infection in mice after a two-dose vaccination regiment. The DNA-launched subunit vaccine is able to decrease infection after a single dose however cellular immunity is increased after mice are given the boost dose. These DNA-launched vaccines can combine the benefits of storage, development, and manipulation of DNA, while increasing the immunogenicity, safety profiles of LAVs and subunit vaccines. These DNA-launched vaccines warrant further consideration for increased testing and evaluation in pre-clinical and clinical trials
RESPIRATORY PARAMETERS, PULMONARY REHABILITATION and SURVIVAL in COVID-19 PATIENTS
No full textBackground: 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
Assessment of Reflective Teaching Practice in Undergraduate Nursing Faculty
No full textThe 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
Nurse Educators' Perspectives and Experiences with Clinical Judgment
No full textSound 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’ C
Interferons in Influenza A Virus and Streptococcus Pneumoniae Co-Pathogenesis
No full textSecondary pneumococcal pneumonia postinfluenza significantly
increases the disease burden associated with influenza A virus (IAV) infection. IAV induced
interferons (IFN) play a crucial role in antiviral immunity. However,
recent reports have indicated that influenza-induced IFN-I and IFN-
γ signaling suppress innate antibacterial immunity by distinct mechanisms,
thereby increasing host susceptibility to secondary bacterial pneumonia. Despite
their detrimental role, the interplay between them remains poorly understood. In
this dissertation, we have investigated the relative importance of IFN-I and IFN-γ
pathways in the pathogenesis of IAV/ Streptococcus Pneumoniae
(SPn) coinfection. Using gene knock-out models and neutralizing in
vivo antibodies, we demonstrated that IFN-I and IFN-γ inhibit acute bacterial
clearance post-IAV infection. However, IFN-γ plays a more critical role.
Additionally, we found that IFN-I signaling is essential for preventing IFN-γ
hyperproduction and animal death during coinfection, indicating the dual role of
IFN-I, which was novel. Moreover, we show that both IFN-I and IFN-γ employ
distinct mechanisms to regulate inflammatory cytokine response and immune cell
recruitment during copathogenesis. Given the dominant role of IFN-γ in the
progression of coinfection, we further investigated the effect of immune
predisposition on susceptibility to coinfection. To that end, we demonstrated that
pathogenicity to coinfection remains distinct between BALB/c and C57BL/6 (B6)
mice that recapitulate Th2- and Th1-biased responses, respectively. Prior infection
with a low-virulent IAV strain (X31) renders B6 mice extremely susceptible to
superinfection compared to the resistant BALB/c mice. We found that neither the
viral nor the bacterial infection alone induced IFN-γ response in both strains of
mice. However, the coinfection resulted in a robust IFN-γ response in the B6 mice,
not the BALB/c mice. Furthermore, this IFN-γ response in the B6 mice inhibited
neutrophil recruitment and innate bacterial clearance. Additionally, we also
demonstrated that neutrophils in BALB/c mice are required for effective bacterial
control. Collectively, our results indicate that Th1-biased immune predisposition
plays an important role in determining the outcome during
IAV/ SPn coinfection. Altogether, our work has demonstrated the relative
importance and the regulation between IFN-I and IFN-γ during the coinfection
pathogenesis, which is imperative for understanding the complex pathogenic
mechanisms
The Impact of An Innovative Online Orientation Program on Graduation among Graduate Nursing Students: A Secondary Analysis
No full textThe current shortage of Advanced Practice Registered Nurses (APRN) in the United States requires innovative programs to increase on-time graduation and decrease attrition. The Master of Science in Nursing (MSN) Online Orientation for Retention Excellence (MORE) Program is one such program. However, the program’s impact on on-time graduation and attrition is not known. The purpose of this study was to examine the impact of the MORE Program on student’s on-time graduation and attrition. Tinto’s Theoretical Model of Student Departure (1993) was used as the guiding theoretical framework. A retrospective secondary
analysis was conducted on all 608 MSN students who enrolled in the Fall 2016 to Fall 2018 at one nursing school located in the southern United States. Logistic regression models were used to examine the association between the MORE Program and the on-time graduation rate and the attrition rate. The models adjusted for the effect of age, sex, program track, and admission GPA.
The study found no statistical difference in the odds of graduating on-time between students who did and did not participate in the MORE Program. However, age, program track, and admission GPA were significant predictors of on-time graduation. For attrition, students who never or only partially participated in the MORE Program had 2 to 3 times higher odds of attrition compared to students who fully participated. Age and program track were also significant predictors of attrition. Online orientation programs should be used in online graduate nursing programs to decrease attrition. Findings from this study could inform nursing educators about establishing online orientation programs and resources to support at-risk students to better prepare online graduate nursing students for successful graduation
Patterns, Variation and Mental Health Impact of Opioid Prescribing after Burn Injury
No full textBurn injury is a severe trauma that can cause debilitating pain, disability and declines in mental health and overall quality of life. Opioids are the mainstay therapy for management of pain after burn injury. In light of the opioid epidemic in the United States and the increased risk of harm associated with use of opioids, we sought to explore the trends, predictors, and impact on mental health of opioid prescribing after burn trauma, using a national commercial insurance database. First, we assessed the trends in opioid prescribing after burn injury in the outpatient setting and explored age, severity, and geographical variation. We found that opioid prescribing declined significantly between 2007 and 2017, however the rates of decline varied significantly among age groups, regions, and injury severity, with patients > 50, the South, and those with more severe burn realizing the least reductions in opioid prescriptions over time. Second, we assessed the rate of prescribing of gabapentinoids, alone or with opioids, over time to determine whether they were used as substitutes for opioid therapy. We found that gabapentinoid prescriptions alone increased significantly between 2012-2018, particularly among those over 50 years old, those residing in the South and the patients with less severe burns. Co-prescriptions with opioids did not differ significantly over time, after adjustment. Finally, we assessed the impact of opioid use on new onset depression, generalized anxiety or post-traumatic stress disorder in the post-burn period. We found that opioid prescribing after burn did not increase the risk for any mental health disorders, however those receiving opioids before burn were significantly more at risk to present with mood or stress disorders afterwards. Our findings support the need for uniform guidelines for the management of burn pain that promote non-opioid alternatives, as well as regular and timely screening for mental health problems in survivors of severe burn injury