Medicine and Health Sciences Commons^™

Developing Deep-Learning Methods For Diagnosis And Prognosis Of Pediatric Progressive Diseases Using Modern Imaging Techniques, Mahdieh Shabanian

Theses and Dissertations (ETD)

Purpose and Rationale. Central nervous system manifestations form a significant burden of disease in young children. There have been efforts to correlate the neurological disease state in tuberous sclerosis complex (TSC) neurological disease state with imaging findings is a standard part of patient care. However, such analysis of neuroimaging is time- and labor-intensive. Automated approaches to these tasks are needed to improve speed, accuracy, and availability. Automated medical image analysis tools based on 3D/2D deep learning algorithms can help improve the quality and consistency of image diagnosis and interpretation for cognitive disorders in infants. We propose to automate neuroimaging analysis …

Identifying The Molecular Cause Of Extreme Endoplasmic Reticulum Dilation In Pediatric Osteosarcoma And Its Relationship To The Disease, Rachael Wood

Theses and Dissertations (ETD)

Pediatric osteosarcoma tumors are characterized by an unusual abundance of grossly dilated endoplasmic reticulum and an immense genomic instability that has complicated identifying new effective molecular therapeutic targets. Here we report a novel molecular signature that encompasses the majority of 108 patient tumor samples, PDXs and osteosarcoma cell lines. These tumors exhibit reduced expression of four critical COPII vesicle proteins that has resulted in the accumulation of procollagen-I protein within ‘hallmark’ dilated ER. Using CRISPR activation technology, increased expression of only SAR1A and SEC24D to physiologically normal levels was sufficient to restore both collagen-I secretion and resolve dilated ER morphology …

Examination Of Antiviral Resistance In Venezuelan Equine Encephalitis Virus, Jasper Lee

Theses and Dissertations (ETD)

Venezuelan equine encephalitis virus (VEEV) is a New World Alphavirus that causes Venezuelan equine encephalitis (VEE), which is characterized by a febrile illness that can progress to neurological disease and death. While no major outbreaks of VEE have occurred since 1995, VEEV is a virus of concern as, in addition to its spread through mosquitos, it can be aerosolized and used as a bioweapon. Unfortunately, there are currently no FDA-approved vaccines or antivirals against VEEV. Efforts have been made to discover small molecules with an inhibitory effect on VEEV, but the potential for emergence of antiviral resistance to these compounds …

Environmental And Genetic Factors Affecting Bone Diseases And Phenotypes In Mouse Models, Wei Dong

Theses and Dissertations (ETD)

Bone diseases and phenotypes are affected in multiple ways. We focused on studying the effects of genetic and environmental factors, especially their impact on bone properties. Firstly, we investigated the effects of β-caryophyllene (BCP), a naturally occurring dietary cannabinoid, on protecting bone from vitamin D deficiency in mice fed on a diet lacking or supplemented with vitamin D (VD). We found that the VD-deficient diet enhanced the length of femur and tibia bones (P<0.05), and increased bone volume (BV; P<0.01) and the trabecular bone volume fraction (BV/TV; P <0.01) compared to the D+ diet. When given BCP-containing diet, mice exhibited higher BV and bone mineral density (BMD; P<0.05) than the control group. The trabecular and cortical bone were also affected by VD and BCP. In addition, the inclusion of dietary BCP improved the serum concentrations of klotho (P < 0.05). In summary, these data indicate that BCP enhances the level of klotho in the serum, leading to improved bone properties and mineralization in an experimental mouse model. Under conditions lacking UV light, the D-deficient diet could affect multiple properties of bone, including trabecular and cortical bone, in mice. The D-deficient diet can also result in weight loss in mice.

My second project is to evaluate the bone properties in a mouse model with Il-1rn mutation. When knockout for IL-1rn, mice of Balb/c genomic background exhibited …

Characterizing And Overcoming Resistance To Aminomethylspectinomycins In Gram-Negative Bacteria, Nisha Das

Theses and Dissertations (ETD)

Spectinomycin (SPC) is a broad-spectrum aminocyclitol antibiotic. Its use in agriculture has led to widespread resistance in enteric bacteria, necessitating the development of more effective analogs. Aminomethyl spectinomycins (amSPC) are modified spectinomycins with increased potency against many bacterial species. These species include Legionella pneumophila, which harbors a chromosomally encoded aminoglycoside modifying enzyme (AME). In this study, we follow up on this observation and examine the extent to which the amSPCs are substrates for AMEs through adenylation (ANTs) and phosphorylation (APH). APH(9)-Ia and ANT(3")(9) were expressed in E. coli BL21(DE3) and purified using the Ni-affinity chromatography. The ability of AMEs to …

The Effect Of Cancer Cachexia Progression On The Feeding Regulation Of Skeletal Muscle Protein Turnover, Brittany R. Franch

Theses and Dissertations (ETD)

Cancer cachexia is defined as the unintentional loss of skeletal muscle mass with or without fat loss that cannot be reversed by conventional nutritional support. Cachexia occurs in ~20% of cancer patients. More specifically, 50% of lung cancer patients, the most common cancer worldwide, develop cachexia. Cachexia occurs most often in lung and gastrointestinal cancers, whereas breast and prostate have the lowest rate of cachexia. Cancer-induced cachexia disrupts skeletal muscle protein turnover (decreasing protein synthesis and increasing protein degradation). Skeletal muscle’s capacity for protein synthesis is highly sensitive to local and systemic stimuli that are controlled by mTORC1 and AMPK …

Ecology Of Hantaviruses In Rodent Reservoirs And Their Early Innate Immune Responses In Human Model Systems, Evan Peter Williams

Theses and Dissertations (ETD)

The spillover of zoonotic RNA viruses is responsible for a great deal of the disease outbreaks in human populations. These spillover events are set to continue due to anthropogenic and environmental changes that impact the distribution of these viruses. The viruses in the family Hantaviridae are classified as one of these emerging zoonotic RNA viruses. The spillover of the viruses in this family are responsible for two severe human diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). These viruses are distributed across the globe and are responsible for a large number of human disease cases with …

Impact Of Central Line Bundle Care On Reduction Of Central Line Associated-Infections: A Scoping Review, Alisha James-Scott Msn, Fnp-C, Rachel Savoy Msn, Fnp-Bc, Donna Lynch-Smith Dnp, Acnp-Bc, Apn, Ne-Bc, Cnl, Tracy Mcclinton Dnp, Ag-Acnp-Bc, Apn

Doctor of Nursing Practice Projects

Purpose/Background Central venous catheters (CVC) are typical for critically ill patients in the intensive care unit (ICU). Due to the invasiveness of this procedure, there is a high risk for central line-associated bloodstream infection (CLABSI). These infections have been known to increase mortality and morbidity, medical costs, and reduce hospital reimbursements. Evidenced-based interventions were grouped to assemble a central line bundle to decrease the number of CLABSIs and improve patient outcomes. This scoping review will evaluate the literature and examine the association between reduced CLABSI rates and central line bundle care implementation or current use.

Methods A literature review was …

Medicated-Assisted Treatment And 12-Step Programs: Evaluating The Referral Process, Candace S. Brown, Chudney Williams, Ryan E. Stephens, Jacqueline Sharp, Bobby Bellflower, Martinus T. Zeeman

Doctor of Nursing Practice Projects

Purpose/Background Overdose deaths in the U.S. from opioids have dramatically increased since the COVID-19 pandemic. Although medicated-assisted treatment (MAT) programs are widely available for sufferers of opiate addiction, many drop out of treatment prematurely. Twelve-step programs are considered a valuable part of treatment, but few studies have examined the effect of combining these approaches. We aimed to compare abstinence rates among patients receiving MAT who were referred to 12-step programs to those only receiving MAT.

Methods In this prospective study, a cohort of participants from a MAT clinic agreeing to attend a 12-step program was compared to 15 controls selected …

The Molecular Mechanisms Of Estrogen Receptor Α On Two Single Nucleotide Polymorphisms To Regulate Wnt Signaling In Osteoblasts, Sarocha Suthon

Theses and Dissertations (ETD)

Osteoporosis is the most common bone metabolic disorder, affecting over 200 million people globally. It is characterized by bone mass depletion and microarchitectural deterioration, leading to bone fragility and susceptibility to bone fracture. Genetic factors, estrogen deficiency, and dysregulation of the WNT signaling pathway contribute to the development of this disease. Genome-wide association studies have predicted that the single nucleotide polymorphisms (SNPs) rs2887571 and rs9921222 associate with low bone mass, but the mechanism of these SNPs has remained unknown. Analysis of osteoblasts from 112 different joint replacement patients reveals that the genotype of rs2887571 correlates with WNT5B expression, and the …

Role Of Smad2 And Smad3 On Adipose Tissue Development And Function, Roshan Kumari

Theses and Dissertations (ETD)

Introduction: Obesity and its associated metabolic syndrome are major medical problems worldwide including United States. Adipose tissue is the primary site of energy storage, playing important roles in health. Adipose tissue also has other critical functions, producing adipocytokines and contributing to normal nutrient metabolism, which in turn play important roles in satiety, inflammation, and total energy homeostasis. Activin A and activin B play important roles in maintaining body composition and energy homeostasis. This dissertation highlights the role of activin/SMADs signaling in adipose tissue development, function, and maintenance.

SMAD2/3 proteins are downstream mediators of transforming growth factor-β (TGFβ) family signaling, including …

Evaluation And Feasibility Of A Head Positioning Intervention In Patients With Intraparenchymal Hemorrhage, Wendy L. Dusenbury

Theses and Dissertations (ETD)

Stroke caused by intraparenchymal hemorrhage (IPH) is most commonly the result of hypertension-induced blood vessel rupture in the brain and is associated with devastating disability and high rates of death. To date, no intervention has improved outcomes in IPH stroke patients; however, head elevation may be one of the most important first steps to promote clinical stability in the hyperacute stage of IPH stroke because of the risk of increased intracranial pressure (ICP) in these patients. Nursing research completed in the late 1970s and early 1980s in patients with increased ICP due to traumatic brain injury showed that elevating the …

Advancing Rna Virus Discovery And Biology With Whole Genome Sequencing, Mariah Katherine Taylor

Theses and Dissertations (ETD)

Two RNA virus families that pose a threat to human and animal health are Hantaviridae and Coronaviridae. These RNA viruses which originate in wildlife continue and will continue to cause disease, and hence, it is critical that scientific research define the mechanisms as to how these viruses spillover and adapt to new hosts to become endemic. One gap in our ability to define these mechanisms is the lack of whole genome sequences for many of these viruses. To address this specific gap, I developed a versatile amplicon-based whole-genome sequencing (WGS) approach to identify viral genomes of hantaviruses and severe acute …

Responding To The Pandemic: A Multicountry Study On Social-Political Factors And Health Outcomes Of Covid-19, Lan Yao

Theses and Dissertations (ETD)

Introduction. Coronavirus Disease 2019 (COVID-19) poses a major global threat to human beings, which has caused devastating consequences of population health, political, and economic crises in many countries. This dissertation was composed of three research activities to study the following aims: (1) review the existing literature focusing on political factors and health outcomes of COVID-19; (2) assess the relationship between democracy and case fatality rate of COVID-19 by controlling for the effect of age, comorbidity, health expenditure, healthcare workforce, and population density; and (3) identify the trajectory pattern cases peak days, deaths peak days, and peak periods.

Methods. We accessed …

The Impact Of The Health Information Technology For Economic And Clinical Health Act On Clinical Pharmacy And Computerized Provider Order Entry, Bailey Deglow

Applied Research Projects

The Health Information Technology for Clinical and Economic Health (HITECH) Act of 2009 encouraged the meaningful use of the electronic health record (EHR) by health care providers in the United States. “Meaningful use” monetary incentives were offered by the Center for Medicare and Medicaid Services (CMS) for health care providers who met standards of documenting in and using the EHR. While clinical pharmacists typically work in clinics and hospitals in the United States, they were not considered eligible professionals who could receive incentives for using the EHR. There is a great deal of literature regarding the use of the EHR …

Adverse Childhood Experiences And Urinary Incontinence In Elementary School Aged Children, Amanda Jill Travis Msn, Fnp-C, Margaret C. Harvey Phd, Aprn, Acnp-Bc, Chfn, Michelle Rickard Dnp, Apnp-C

Doctor of Nursing Practice Projects

Purpose/Background: Adverse Childhood Experiences (ACEs) have an impact on health throughout the lifespan (Filletti et al., 1999; Hughes et al., 2017). These experiences range from physical and mental abuse, substance abuse in the home, parental separation or loss, financial instability, acute illness or injury, witnessing violence in the home or community, and incarceration of family members (Hughes et al., 2017). Understanding and screening for ACEs in children with urinary incontinence can help practitioners identify psychological stress as a potentially modifiable risk factor.

Methods: A 5-month chart review was performed identifying English speaking patients ages 6-11 years presenting to the outpatient …

Analyzing Point Of Care Tools Through Faculty, Resident, And Stakeholder Buy-In: A Cautionary Tale, J. Michael Lindsay, David Petersen, Abagail Pujol, Martha Earl

Southern Chapter/Medical Library Association Annual Conference

Purpose: Costs for Preston Medical Library’s primary point-of-care (POC) clinical tool have increased to half of the acquisitions budget, while user affiliation data have not been provided to facilitate cost sharing. In response, user preferences for POC tools were analyzed to determine a viable, less expensive alternative to the current subscription.

Setting/Participants/Resources: Faculty and residents at the University of Tennessee Graduate School of Medicine (GSM), and other clinical staff at the University of Tennessee Medical Center (UTMC), a 685-bed teaching hospital.

Methodology: At the direction of school leadership, a working group of library staff, resident physicians, and medical faculty members …

Integrating Digital Health Technology To Alleviate Caregiver Burden, Patricia Ann Hunt

Applied Research Projects

The elder population in our country is growing at an exponential pace. Studies have shown that elders who are aged 80 years and older are projected to suffer from age related issues such as Alzheimer’s, dementia, and osteoporosis and will need assistance with Long Term Services and Support (LTSS). Additionally, many elders are also projected to suffer from more severe chronic illnesses such as diabetes, cancer, and heart related illnesses. Because many of these elders are aging in place, residing in their own homes, they will require the services of at home assistance, which high probability will be a neighbor, …

Transversus Abdominis Plane Block: A Scoping Review, Liam Maher, Leanne Orians, Gabrielle Pappas, Lanny Coker Dnsc, Crna

Doctor of Nursing Practice Projects

The purpose of this project is to provide an overview of the literature on the analgesic effects of transverse abdominal plane (TAP) block and its effectiveness in reducing opioid consumption.

Intraoperative Dexmedetomidine For Reduction Of Postoperative Delirium In The Elderly: A Scoping Review, Gregory B. Harris Bsn, Rn, Srna, Brooke N. Hatchell Bsn, Rn, Srna, Davelin D. Woodard Bsn, Rn, Srna, Dwayne Accardo Dnp, Aprn, Crna

Doctor of Nursing Practice Projects

Background/Purpose: Post-operative delirium leads to significant morbidity in elderly patients, yet there is no regimen to prevent POD. Opioid use in the elderly surgical population is of the most significant risk factors for developing POD. The purpose of this scoping review is to recognize that Dexmedetomidine mitigates cognitive dysfunction secondary to acute pain and the use of narcotic analgesia by decreasing the amount of norepinephrine (an excitatory neurotransmitter) released during times of stress. This mechanism of action also provides analgesia through decreased perception and modulation of pain.

Methods: The authors developed eligibility criteria for inclusion of articles and performed a …

Intraoperative Administration Of An Nsaid And An Opioid Vs. An Opioid Alone Effect On Postoperative Ileus Development, Brooke H. Ulsh, Delaney N. Vedros, Rebekah G. Whaley, Sharon Little Dnp, Aprn, Fnp-Bc

Doctor of Nursing Practice Projects

The purpose of this DNP project is to examine what is known from existing literature about postoperative ileus development in the adult surgical patient population after receiving intraoperative opioids versus a combination of intraoperative opioids and NSAIDs.

Pain Control: Opioid Vs. Nonopioid Analgesia During The Immediate Postoperative Period, Shamsie M. Lumpkin Bsn, Srna, Isaac W. Parrish Bsn, Srna, Austin S. Terrell Bsn, Srna, Dwayne S. Accardo Dnp, Aprn, Crna

Doctor of Nursing Practice Projects

Background Opioid analgesia has become the mainstay for acute pain management in the postoperative setting. However, the use of opioid medications comes with significant risks and side effects. Due to increasing numbers of prescriptions to those with chronic pain, opioid medications have become more expensive while becoming less effective due to the buildup of patient tolerance. The idea of opioid-free analgesic techniques has rarely been breached in many hospitals. Emerging research has shown that opioid-sparing approaches have resulted in lower reported pain scores across the board, as well as significant cost reductions to hospitals and insurance agencies. In addition to …

Dexmedetomidine Vs Fentanyl In Attenuating The Sympathetic Surge During Endotracheal Intubation: A Scoping Review, Alexandra Schwieger, Kaelee Shrewsbury, Paul Shaver, Dwayne Accardo Dnp, Crna

Doctor of Nursing Practice Projects

Purpose/Background Direct laryngoscopy and endotracheal intubation after induction of anesthesia can cause a reflex sympathetic surge of catecholamines caused by airway stimulation. This may cause hypertension, tachycardia, and arrhythmias. This reflex can be detrimental in patients with poor cardiac reserve and can be poorly tolerated and lead to adverse events such as myocardial ischemia. Fentanyl, a potent opioid, with a rapid onset and short duration of action is given during induction to block the sympathetic response. With a rise in the opioid crisis and finding ways to change the practice in medicine to use less opioids, dexmedetomidine, an alpha 2 …

Postoperative Nausea And Vomiting Implications In Neostigmine Versus Sugammadex, Corey Lee Johnson, Colton Bradley James, Sarah Grace Traughber, Charles Anthony Walker, Dwayne Accardo Dnp, Aprn, Crna

Doctor of Nursing Practice Projects

Purpose/Background: Postoperative nausea and vomiting (PONV) is a frequent complaint in the postoperative period, which can delay discharge, result in readmission, and increase cost for patients and facilities. Inducing paralysis is common in anesthesia, as is utilizing the drugs neostigmine and sugammadex as reversal agents for non-depolarizing neuromuscular blockers. Many studies are available that compare these two drugs to determine if neostigmine increases the risk of PONV over sugammadex. Sugammadex has a more favorable pharmacologic profile and may improve patient outcomes by reducing PONV.

Methods: This review included screening a total of 39 studies and peer-reviewed articles that looked at …

Opioid Free Anesthesia To Prevent Post Operative Nausea/Vomiting, Aleksander Acred, Milena Devineni, Lindsey Blake, Cindi Dabney Dnp, Crna

Doctor of Nursing Practice Projects

Purpose The purpose of this study is to compare the incidence of post-operative nausea and vomiting (PONV) in opioid-utilizing and opioid-free general anesthesia. Background PONV is an extremely common, potentially dangerous side effect of general anesthesia. PONV is caused by a collection of anesthetic and surgical interventions. Current practice to prevent PONV is to use 1-2 antiemetics during surgery, identify high risk patients and utilize tracheal intubation over laryngeal airways when indicated. Current research suggests minimizing the use of volatile anesthetics and opioids can reduce the incidence of PONV, but this does not reflect current practice.

Methods In this scoping …

Effects Of Genetics And Sex On Hippocampal Gene Expression And Adolescent Behaviors Following Neonatal Ethanol Exposure In Bxd Recombinant Inbred Mice, Jessica A. Baker

Theses and Dissertations (ETD)

Fetal alcohol spectrum disorders (FASD) are the leading preventable neurodevelopmental disorders in the western world. A hallmark symptom of FASD is cognitive and learning deficits that present in early childhood and continue throughout adulthood. Teratogenic effects of alcohol include increased cell death in the hippocampus, a brain region critically important in learning and memory. Genetics have been shown to have a role in the severity of alcohol’s teratogenic effect on the developing brain. Previous work in our lab identified differential vulnerability to ethanol-induced call death in the hippocampus using fourteen BXD strains and the two parental strains. The goal of …

Taste Learning In Insular Cortex: Plasticity Is Influenced By Experience Type, Stephanie Marie Staszko

Theses and Dissertations (ETD)

The gustatory cortex (GC) has long been studied as the main cortical area encoding taste stimuli and likely integrates sensory, visceral, and emotional information to guide taste-related behaviors. However, our understanding of cortical taste coding on a single-cell level has only become clear in recent years. The anatomical location of GC on the lateral and ventral surface of the brain makes it difficult to target with traditional imaging methods. Thus, much of what we know about cortical taste coding and cortical taste plasticity has been derived either from multiunit electrode recordings or anesthetized imaging experiments, techniques which lack the ability …

Iatrogenic Electrocautery Damage And Cellular-Based Corrosion Of Total Joint Arthroplasty Biomaterials, Kirsten Carol Miller

Theses and Dissertations (ETD)

Introduction. The number of patients undergoing a Primary Total Knee Arthroplasty (PTKA) has been increasing steadily each year. Of those PTKA patients, 20% report long-term pain and/or some functional deficit. Cobalt-Chromium-Molybdenum (CoCrMo) alloy is one of the most used materials in Total Joint Arthroplasty (TJA) implants due the material’s high strength, high corrosion resistance, and biocompatibility. The release of metal ions and potential occurrence of metallosis in TJA has been shown to be detrimental to the longevity of the implant. The mechanisms leading to this increase in metal ion concentrations have been up for debate, with some believing it is …

Near-Field Electrospinning And Characterization Of Biodegradable Small Diameter Vascular Grafts, William E. King Iii

Theses and Dissertations (ETD)

The ideal “off the shelf” tissue engineering, small-diameter (< 6 mm inner diameter (ID)) vascular graft hinges on designing a template that facilitates transmural ingrowth of capillaries to regenerate an endothelized neointimal surface. Previous traditionally electrospun (TES) approaches to create bioresorbable vascular grafts lack the pore sizes required to facilitate transmural capillary ingrowth required for successful in situ neovascular regeneration. Therefore, the ability to create scaffolds with program-specific architectures independent of fiber diameter via the relatively recent sub-technique of near-field electrospinning (NFES) represents a promising solution to create tissue engineering vascular grafts. These programmed large pore sizes are anticipated to promote in situ regeneration and improve the outcomes as well as the quality of life of patients with arterial disease.

In this dissertation, we manufactured via NFES as well as characterized biodegradable polydioxanone (PDO) small-diameter vascular grafts. Chapter 1 introduces the need for off-the-shelf, small-diameter vascular grafts to facilitate in situ regeneration, the process and pore size limitations of TES vascular grafts, and the promising use of NFES to develop precisely tailored PDO vascular grafts. Chapter 2 describes the process of NFES and details the current progress in NFES of biomedical polymers as well as the major limitations that exist in the field. Chapters 3, 4, and 5 contain primary research …

Combating Hiv-1 By Targeting Drug Efflux Transporters On The Macrophage Reservoir, Ying Mu

Theses and Dissertations (ETD)

Introduction. HIV-1 eradication has not been achieved so far due to the existence of the cellular reservoir in which the virus can reside and replicate even under antiretroviral drug therapy (ART). Infected macrophages, which represent a long-term viral reservoir have been shown to lead to viral rebound independently. In response to the environmental stimuli, macrophages can be polarized into different phenotypes: the pro-inflammatory M1 and the anti-inflammatory M2. Tobacco smoking and alcohol drinking, which are prevalent among people who are living with HIV-1, have been shown to promote HIV-1 progression and decrease the efficacy of antiretroviral drugs. A commonly …