University of Tennessee Health Science Center
UTHSC Digital Commons (University of Tennessee Health Science Center)Not a member yet
1172 research outputs found
Sort by
Evaluating HPV Vaccination Adherence Amongst Teenagers Ages 12-18
Get PDFHuman papillomavirus (HPV) is a sexually transmitted infection that can cause genital warts and different cancers. According to the CDC, 85% of people will get an HPV infection in their lifetime. HPV infections have decreased significantly since the implementation of the HPV vaccine. Data has shown 90% of cancers caused by HPV can be prevented with administration of HPV vaccination. Current guidelines recommend vaccination administration as early as 9 years of age. This quality improvement project will evaluate HPV vaccination rates amongst teenagers ages 12-18
Esmolol Compared to Fentanyl for Hemodynamic Attenuation during Intubation: A Scoping Review
Get PDFPurpose/Background
Endotracheal intubation and laryngoscopy potentiate the cardiovascular response in the form of hypertension, tachycardia, and ventricular arrhythmias. Suppression of this adrenergic response is necessary to ensure patient safety. Currently, anesthesia providers employ many methods to attenuate the sympathetic response without established guidelines. As such, our project aimed to determine the effectiveness of fentanyl compared to esmolol in attenuating the hemodynamic response during laryngoscopy and endotracheal intubation within the first five minutes and throughout the intraoperative period.
Methods
A literature review was completed of ten critically appraised articles from the years 2011-2022. Articles in the review included randomized control studies, peer reviews, evidence-based practice, comparative studies, and meta-analyses. All articles included must have addressed fentanyl or esmolol groups associated with hemodynamics before and after intubation. A level of evidence outcomes table was composed to provide a synthesis of results from the ten chosen articles.
Results
Of the multiple articles reviewed, the majority concluded fentanyl was the better choice to administer before induction for attenuating hemodynamic responses to intubation. Many studies differ in the patient populations evaluated, but overall, fentanyl caused the least number of hypertensive episodes. Esmolol was typically more effective on the heart rate response, while the combination of the two medications was more effective on the arterial pressure. However, such combination resulted in significant post-intubation hypotension, requiring an immediate response.
Implications for Nursing Practice
Results provided in this scoping review afforded the authors a diverse level of evidence that using fentanyl or esmolol can attenuate hemodynamic responses to endotracheal intubation. The individual need of each patient is highly regarded as the decision-making aspect of each case, with fentanyl as the preferred agent for overall hemodynamic stability. These findings suggest further evaluations regarding patient individualization are needed when choosing the appropriate drug for attenuating the hemodynamic response to intubation
ICU Delirium: Detection with and without CAM-ICU Screening
Get PDFPurpose/Background
Delirium is a form of brain malfunction marked by abnormalities in cognition, disorientation, memory, and awareness. This scoping review\u27s aim is to examine bodies of research on the effects of length of stay (LOS) in the ICU using Confusion Assessment Method-Intensive Care Unit (CAM-ICU).
Methods
Adults age 18 and older admitted to the ICU, of any race or ethnicity, and any gender were all included in the study articles. Nine articles satisfied the search criteria after publications underwent rapid critical appraisal. Results were evaluated for ICU LOS, hospital LOS, mortality, restraint use, medication use, delirium screening tool use, and screening tool efficacy.
Results
One article demonstrated a decrease in ICU LOS with CAM-ICU delirium detection. Four articles demonstrated detection of delirium by using the CAM-ICU tool. Hospital LOS without CAM-ICU showed increased LOS in three articles and decreased LOS in one article. No effect was reported or examined for ICU LOS without delirium detected by CAM-ICU. Mortality increased for patients with delirium detected by CAM-ICU and non-CAM-ICU tool in two articles and decreased in one article. Mortality without delirium decreased in one article. Other outcomes such as high-risk medication and restraint usage were found in four other articles. These articles demonstrated our desired outcomes and highlight the need for future research on the impact of LOS with early detection of delirium with the CAM-ICU screening tool.
Implications for Nursing Practice
As nurse practitioners, it is our responsibility to be aware of the effects of ICU delirium and to promote the use of CAM-ICU as evidence-based practice to detect delirium to lessen its effects, which in turn reduces mortality and hospital LOS.
Keywords: ICU and hospital length of stay (LOS) for CAM-ICU, ICU and hospital LOS for non-CAM tool delirium mortality with delirium, mortality without delirium, restraint usage, high-risk medication usage, effectiveness of screening tool, and screening tool usag
Utilizing Stakeholder Input within the Tennessee Heart Health Network to Improve Cardiovascular Health Outcomes in Tennessee
Get PDFBackground: Tennessee ranks sixth nationwide for most deaths related to heart disease. The Tennessee Heart Health Network (TN-HHN), an initiative coordinated by the Tennessee Population Health Consortium (TN-PHC), was created to combat this issue. The TN-HHN is a statewide network of primary care practices, health systems, and academic centers committed to implementing patient-centered outcomes research (PCOR) approaches to demonstrably improve cardiovascular disease (CVD) health outcomes and health equity across Tennessee.
Objective: Evaluate stakeholder experiences in participating in the Network in an effort to assess partner satisfaction and improve the TN-HHN as a whole.
Methods: Eligible stakeholders were invited via email to complete an electronic survey to give their input on the formation, evolution, and development of the TN-HHN. The survey was programmed and administered via REDCap and ran from June 22 ─ July 8, 2022. It was comprised of 17 required multiple-choice questions and five optional open-ended questions related to diversity, partnership opportunities, membership roles, meeting productivity, goals and success of the Network, and knowledge of PCOR and priority heart health issues.
Results: Of the 156 stakeholders who were invited, 46 (29.5%) completed the survey. There was a high level of agreement on the multiple-choice questions; at least 50% of participants responded approvingly (selected “agree” or “strongly agree”) on every question, with an average of 79.5% total approval on all questions. The highest-scoring quantitative questions had an approval rating of at least 85% and mainly pertained to understanding and supporting the goals of the Network and feeling comfortable and valued during Network meetings. The lowest-scoring quantitative questions concerned Network diversity and meeting productivity and efficiency.
Discussion: Most of the survey responses were positive, demonstrating an overall high level of stakeholder satisfaction. Members indicated that they were most appreciative of the opportunities they have had to form partnerships with other health care organizations and to learn more about their patient-care strategies. Based on the multiple-choice and open-ended questions, there is room for improvement regarding the diversity of the Network and the efficiency of Network meetings
The Impact of Telehealth in Urgent Care Settings
Get PDFTelehealth is an emerging modality of patient care and has since expanded to urgent care facilities. Urgent care facilities have been around for decades; however, along with telehealth, it has only grown in popularity in recent years due to the COVID-19 pandemic. However, the implementation and usage of telehealth in urgent care facilities is dependent on the provider being able to use it. This study aimed at looking at the perspective of the provider on the implementation and usage of telehealth in the urgent care setting
Molecular and Cellular Investigations of Prader-Willi Syndrome
Get PDFPrader-Willi syndrome (PWS) is a complex multigenic neurodevelopmental disorder resulting in hypotonia, developmental delay, hypogonadism, sleep dysfunction and childhood onset obesity affecting 1 in 10,000 to 30,000 individuals. PWS is an imprinting disorder that is caused by a loss of expression of maternally imprinted genes in the 15q11.2-q13 region including NDN, MAGEL2, SNRPN/SNURF, and a cluster of snoRNAs. The majority of cases are caused by inheriting a paternal allele deletion of this region (65-75%) and a smaller number are caused by chromosome 15 maternal uniparental disomy (UPD) (20-30%) or imprinting center defects (1-3%). Here, we used dental pulp stem cells (DPSC), differentiated to neuronal cultures, to investigate the molecular and cellular phenotypes of PWS neurons. DPSC are multipotent stem cells that accurately recapitulate the epigenetic signature of embryonic stem cells and can differentiate to a variety of cell types. Our group has collected over 40 individual PWS lines across the different genetic subgroups. In Chapter 2, we investigated the transcriptional differences in PWS subtypes. While the UPD subtype has milder classical PWS phenotypes, there is an increased risk of developing autism spectrum disorder (ASD) (30% versus 18%) and cycloid psychosis. Using RNA sequencing (RNAseq), we found a global decrease in mitochondrial transcript expression and a mitochondrial aggregate phenotype in PWS UPD +ASD neurons. In Chapter 3, we optimized a bioluminescent assay to visualize the circadian rhythms in PWS neurons. Additionally, we used this assay to analyze circadian rhythms in neurons from individuals with Schaaf-Yang syndrome (SYS), a similar syndrome resulting from mutations in MAGEL2. Using this assay, we found discordant circadian cycling in both PWS and SYS. We also identified two distinct period length phenotypes in PWS neurons that were significantly different than neurotypical control neurons. In Chapter 4, we used a novel approach to single-cell sequencing (SPLiT-Seq) to identify transcriptional differences between neuronal populations from PWS and neurotypical control subjects. In addition to finding several transcripts differentially expressed that are related to PWS phenotypes such as hypogonadism and endocytic recycling, we found a delay in neurogenesis in the PWS neurons. In Chapter 5, we focused our attention on another obesity disorder for comparison. We used RNAseq to determine the transcriptional similarities and differences between PWS, Rapid-Onset Obesity with Hypothalamic Dysregulation, Hypoventilation, and Autonomic Dysfunction (ROHHAD) and Congenital Central Hypoventilation syndrome (CCHS). ROHHAD presents with several key similarities to PWS including rapid-onset obesity and hypothalamic dysfunction. In this study, we found six transcripts differentially expressed in both PWS and ROHHAD and that these transcripts were not related to an obesity pathway or hypothalamic function. Finally, I discussed how the assays and methods described here provide a pipeline for investigating other neurogenetic disorders and how the data discussed in each of these chapters connects to possible defects caused by the spectrum of PWS genetic changes
Discovery of Inhibitors of Inhibitors of Apoptosis Proteins and Novel Tubulin Polymerization Inhibitors as Potential Anticancer Agents
Get PDFThe global impact of cancer as a significant public health concern is undeniable. According to the annual report by the American Cancer Society, projections for 2023 estimate 1,958,310 new cancer cases and 609,820 cancer-related deaths in the US. Recent years have seen significant progress in cancer treatment; however, existing therapies face several challenges. Cytotoxic agents-based chemotherapy often has low therapeutic index and encounters drug resistance shortly after initiation, while immunotherapies exhibit low response rates that vary between patients. As a result, there is a pressing need for the development of novel and effective cancer treatment. The work presented here focuses on the identification of new anticancer agents by targeting three important cancer targets: survivin, MDM2, and tubulin. Survivin, a member of the inhibitor of apoptosis proteins (IAPs) family, serves as both an apoptosis suppressor and a pivotal player in cell division. Its significance as a cancer drug target arises from its heightened expression in various human cancers, juxtaposed with its minimal presence in fully differentiated normal tissues. Additionally, survivin is involved in cancer cell resistance against chemotherapy and radiation. Preclinically, downregulation of survivin expression or function has been shown to impede tumor growth, induce apoptosis, and sensitize tumor cells to radiation and chemotherapy in different human tumor models. Chapter 2 describes our discovery of a series of novel survivin inhibitors based on the hydroxyquinoline scaffold from our previously reported lead compound, MX-106. MX-106 selectively downregulated survivin protein levels and induced apoptosis in melanoma A375 and prostate PC3 cancer cells. A new series of MX-106 analogs were designed, synthesized, and tested against a panel of melanoma, breast cancer, and ovarian cancer cell lines. The most promising compound from this study is referred to as compound 12b with an average IC50 value of 1.4 µM. 12b retained its potency against multidrug-resistant melanoma cells (MDA-MB-435/LCC6MDR1) that overexpress P-glycoprotein (P-gp). 12b selectively reduced survivin protein levels, while negligibly affecting other closely related members in the IAP family proteins, leading to pronounced cancer cell apoptosis. In vivo, 12b significantly inhibited melanoma tumor growth in a human A375 melanoma xenograft model. Further evaluation using an aggressive orthotopic ovarian cancer mouse model showcased the high efficacy of 12b in suppressing primary tumor growth in ovaries and hindering tumor metastasis to multiple peritoneal organs. These results strongly suggest that the hydroxyquinoline scaffold, exemplified by 12b exhibits the potential to selectively target survivin and holds promise for further advancement in preclinical development for potential use as effective anticancer agents. An additional promising target for anticancer treatment is the oncogene MDM2. MDM2 is frequently amplified or overexpressed in various human cancers. MDM2 negatively regulates the tumor suppressor p53, inhibiting its function and promoting cancer growth. MDM2 also interacts with other molecules involved in oncogenesis such as the anti-apoptotic protein X-linked inhibitor of apoptosis protein (XIAP). The C-terminal RING domain of MDM2 binds to the internal ribosome entry site (IRES) of the XIAP mRNA and enhances the IRES-dependent translation of XIAP, which results in increased expression of XIAP and resistance to anticancer treatment. On the other hand, binding of XIAP IRES to the RING domain of MDM2 inhibits MDM2 homodimerization and self-ubiquitination, which results in increased MDM2 protein stabilization. This leads to higher levels of MDM2 protein, along with increased XIAP expression, which collectively contributes to cancer progression and drug resistance. Therefore, simultaneous inhibition of MDM2 and XIAP is anticipated to restore the tumor-suppressing role of p53 in wild type p53 (p53WT) tumor cells, similar to existing MDM2 inhibitors that disrupt MDM2-p53 binding, while additionally inducing apoptosis in p53-deficient cancer cells. We have previously identified JW-2-107, a dual MDM2 and XIAP inhibitor. In Chapter 3, we conducted a detailed analysis of the structure-activity relationships (SAR) of the tetrahydroquinoline scaffold of JW-2-107, including screening the new JW-2-107 analogs against a panel of human cancer cell lines including three p53WT cell lines and one p53 mutant cell line. Among the thirty-one newly synthesized JW-2-107 analogs, compound 3e showed the best antiproliferative activity with IC50 values of 0.2, 1, 1.5, and 5.3 μM against EU-1, A375, MDA-MB-231, and 22Rv1 cell lines, respectively. Analog 3e decreased MDM2 and XIAP protein levels while simultaneously promoting p53 expression. Compared to AMG-232, a potent MDM2-p53 inhibitor in clinical trials, 3e showed potency in the p53-mutant MDA-MB-231 cell line while AMG-232 was not active. When tested on a human 22Rv1 prostate cancer xenograft model, compound 3e effectively suppressed tumor growth in vivo. In light of these findings, the tetrahydroquinoline scaffold, represented by compounds like 3e and the earlier lead compound JW-2-107, has the potential to effectively target both MDM2 and XIAP simultaneously and is promising for further preclinical development. Colchicine binding site inhibitors (CBSIs) bind to tubulin heterodimers, disrupting microtubule dynamics, interfering with the mitotic spindle machinery, and inducing mitotic arrest in the G2/M phase, ultimately leading to apoptotic cell death. Unlike the clinically used antitubulins, taxanes and vinca alkaloids, CBSIs are less prone to several known clinical taxanes resistance mechanisms and possess improved aqueous solubility. Our lab previously reported the discovery of VERU-111, a potent and orally bioavailable CBSI with potent preclinical efficacy in multiple tumor models and preliminary clinical efficacy in metastatic castration-resistant prostate cancer patients. Chapter 4 delineates our discovery process of a series of novel CBSIs derived from VERU-111. Those newly synthesized compounds were tested against four different cancer cells, including a multidrug-resistant cancer cell line. The in vitro results showed that several compounds in this series have better anti-proliferative activities than VERU-111. The best two compounds 11b and 11h displayed IC50 values of 0.6 and 1 nM in melanoma and 1.3 and 1.7 nM in prostate cancer cell lines, respectively. Compared with paclitaxel, the new compounds showed advantages in overcoming multiple drug resistance. The mechanism of action for 11b was investigated using X-ray crystallography, tubulin polymerization assay, and cell cycle analysis. In vivo, 11b and 11h significantly inhibited paclitaxel-resistant PC-3 (PC-3/TxR) prostate cancer tumor growth, disrupted tumor angiogenesis, and led to tumor cell apoptosis. Collectively, 11b and 11h represent promising cancer drug candidates for further development
Exogenous Mitochondrial Transfer and IL-6: Modulating Adipocyte Metabolism in Obesity-associated Dysregulation
Get PDFObesity, a global health epidemic, poses significant challenges to public well-being due to its complex interplay of metabolic dysregulation, inflammation, and associated comorbidities. Mitochondria, central to ATP production, lipid metabolism, and thermogenesis, play a crucial role in modulating white adipose tissue metabolism. This thesis explores an innovative strategy for addressing mitochondrial dysfunction in obesity which is a critical aspect of this multifactorial problem. The research findings presented herein uncover the impact of introducing exogenous mitochondria into NIH3T3-L1 adipocytes on various aspects of adipocyte function. The key discoveries of this study include a remarkable upregulation of energy expenditure genes, notably Ucp1, Dio2, Ppara, and Ppargc1a, upon exposure to exogenous mitochondria, thereby promoting a favorable shift in metabolic profiles within white adipocytes. Mitochondria therapy also appeared to stimulate mitochondrial biogenesis through an increase in Ppara and Ppargc1a expression. Mitochondrial therapy also led to reduced lipid content, indicating a potential means to mitigate adipocyte hypertrophy. Additionally, the release of free fatty acids and glycerol was elevated, reflecting enhanced lipolysis. Thus, this approach showed significant potential for improving energy expenditure and oxidative capacity within adipocytes. Surprisingly, mitochondrial therapy resulted in increased IL-6 levels, contradicting earlier studies showing IL-6 reduction in other injury models. The role of IL-6 in adipose tissue metabolism and obesity has been extensively studied, and this research suggests a possible link between the observed beneficial effects of mitochondria therapy and IL-6 signaling. To test this hypothesis, the study examined the impact of IL-6 neutralization on the metabolic benefits mediated by mitochondrial therapy. Neutralizing IL-6 led to a substantial decrease in the expression of genes associated with energy expenditure, oxidative capacity, and lipid metabolism. This effect highlights the significance of IL-6 in the mechanism of action of mitochondria therapy. In summary, this thesis offers insights into the potential therapeutic implications of mitochondrial transfer in addressing obesity-related metabolic dysregulation. By elucidating specific mechanisms, it contributes to the development of clinically safe treatment options in the ongoing battle against obesity.
How Does School-Based Depression Education Effect Depression Scores: A Scoping Review
Get PDFPurpose:
The purpose of this scoping review is to provide a detailed look into depression education courses among adolescents, ages 10-19 years old, and determine if the adolescents’ knowledge, attitudes, and beliefs regarding depression are impacted.
Specific Aims: •Determine the impact of a school-based depression education program •Evaluate programs for early knowledge and prevention of depression •Compare the current school curriculum with the addition of depression educatio
Perspective on the Utilization and the Outcome of Digital Tools to Manage Chronic Diseases
Get PDFThe increasing aging population and the prevalence of chronic diseases among lower socioeconomic groups have led to higher healthcare spending on chronic care management. In this paper, the study revolves around the utilization of Information and Communication Technology (ICT) for the management of chronic diseases, with a particular focus on the elderly population. The study examines various digital health interventions, including eHealth, mHealth, electronic health records, remote monitoring, wearable devices, clinical decision support systems, telehealth, and telemedicine, in the context of chronic disease management. The opportunities, strengths, and weaknesses of digital technology are discussed, highlighting the potential benefits of ICT in improving healthcare outcomes and reducing the severity of chronic conditions. The paper also addresses the barriers to the adoption of digital health interventions, such as lack of skills, privacy concerns, limited access to high-quality healthcare, and disparities in internet connectivity. Despite these barriers, the integration of ICT in healthcare has shown promising results, empowering patients, enhancing self-management, reducing relapse, and increasing patient participation. The study concludes by emphasizing the significance of digital health technology in addressing the challenges posed by the aging population and chronic diseases, while also acknowledging the need for further research and policy considerations for effective implementation