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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

Feasibility And Acceptability Of Using Mobile Health Apps In Underserved Patients With Diabetes, Jieyu Luo

Theses and Dissertations (ETD)

Introduction. Diabetes mellitus is a condition with a growing morbidity and mortality burden. An estimated 30 million adults currently live with diabetes, with each individual spending over $9500 annually on medical care. The successful management of diabetes is a lifelong endeavor. This involves balancing a variety of factors including diet, medications, and glucose monitoring. It has been well established that successful control of diabetes depends largely upon patients’ daily lifestyle habits and activities. Not all patients, however, have the resources necessary for effective diabetes management. Health disparities lead to a higher rate of diabetes development in minority and poor populations. …

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 …

Genomic Characterization Of Sickle Cell Mouse Models For Therapeutic Genome Editing Applications, Kaitly Jensen Woodard

Theses and Dissertations (ETD)

Sickle cell disease (SCD) is caused by a mutation of the β-globin gene (HBB), resulting in abnormal hemoglobin molecules that polymerize when deoxygenated, forming “sickle” shaped red blood cells (RBCs). Sickle RBCs lead to anemia, multi-organ damage and pain crises, beginning the first year of life. The onset of symptoms coincides with the developmental switch of β-like globin gene expression from fetal stage γ-globin to adult stage β-globin, resulting in a shift from fetal hemoglobin (HbF, α2γ2) to adult hemoglobin (HbA, α2β2). Some individuals harbor rare genetic variants in the extended β-globin gene cluster that cause constitutively elevated postnatal HbF, …

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 …

Antibiotic Tolerance And Heteroresistance: Associated Fitness Costs And Potential In Evading Antibiotic Killing, Tina H. Dao

Theses and Dissertations (ETD)

Streptococcus pneumoniae is a prominent human pathogen that causes both invasive and non-invasive diseases, such as otitis media, pneumonia, meningitis, and bacteremia. Although it is frequently an asymptomatic colonizer of the human nasopharynx, S. pneumoniae is a major cause of morbidity and mortality in the immune compromised population, young children, and the elderly. Up until the 1970s, S. pneumoniae was susceptible to almost all antibiotics. Since then, this pathogen has gained resistance to a variety of antibiotic treatments, including beta-lactams, macrolides, and fluoroquinolones.

In the first chapter, we focused on fluoroquinolone resistance in S. pneumoniae. Fluoroquinolones are one of the …

Identification Of Effectors Of Synergistic Lethality In Candida Albicans-Staphylococcus Aureus Polymicrobial Intra-Abdominal Infection, Olivia Adele Todd

Theses and Dissertations (ETD)

Candida albicans, an opportunistic fungal pathogen, and Staphylococcus aureus, a ubiquitous pathogenic bacterium, are among the most prevalent causes of nosocomial infections and cause severe morbidity and mortality. Moreover, they are frequently coisolated from central venous catheters and deep-seated infections, including intra-abdominal sepsis. Relatively little is known about the complex interactions and signaling events that occur between microbes and even less so how microbial “cross-talk” shapes human health and disease.

Using a murine model of polymicrobial intra-abdominal infection (IAI), we have previously shown that coinfection with C. albicans and S. aureus leads to synergistic lethality whereas monomicrobial infection is nonlethal. …

Effects Of Social Determinants Of Health In Progression To Type 2 Diabetes, Folabi I. Ariganjoye

Applied Research Projects

The prevalence of prediabetes and diabetes in the United States and around the world has increased faster than expected in the last 30 years. The economic burden this costs a nation can be astronomic both in terms of expense and loss in productivity. One-third of U.S. adults, 86 million people, have prediabetes. Effective management is needed that can reach these 86 million, and others at high risk, to reduce their progression to diagnosed Type 2 diabetes. After the literature review, there was not enough literature to support how these led to the progression to diabetes. The abundant literature is centered …

Delineating The Upc2a Regulon In Candida Glabrata, Yu Li

Theses and Dissertations (ETD)

Candida glabrata is the second most common cause of invasive candidiasis. Intrinsic resistance has greatly limited the utility of the triazole antifungal, fluconazole, in the treatment of invasive fungal infection. The transcription factor Upc2 regulates the expression of sterol biosynthesis genes in yeast. Disrupting UPC2A in C. glabrata greatly increases its susceptibility to fluconazole (FLU) in both FLU-susceptible and -resistant clinical isolates. Therefore, the Upc2A and its target genes represent a potential pathway for overcoming FLU resistance in C. glabrata. We aimed to delineate the Upc2A regulon to determine its target genes involved in FLU resistance. Transcriptome sequencing (RNA-seq) analysis …

Muc13 Enhances Colorectal Cancer Metastasis, Kyle Doxtater

Theses and Dissertations (ETD)

Colorectal cancer (CRC) is one of the most prevalent cancer worldwide with a 5% lifetime incidence in developed countries. It is third most common cause of cancer related death in the United States and the second deadliest when men and women are combined. Encouragingly due to changes in dietary lifestyle, screening colonoscopy, and advancement in treatments the mortality has decreased in recent years. Most sporadic CRCs develop from polyploid adenomas and are preceded by intramucosal carcinomas (stage 0), which can progress into more malignant forms. This developmental process is known as the adenoma-carcinoma sequence. Early detection and endoscopic removal are …

Effectiveness Of Ehr-Depression Screening Among Adult Diabetics In An Urban Primary Care Clinic, Filipina C. Schnabel Md, Mph, Msn, Fnp-Bc, Danielle Aldridge Msn, Fnp-C, Laura Reed Dnp, Fnp-Bc

Doctor of Nursing Practice Projects

Background Diabetes mellitus (DM) and depression are important comorbid conditions that can lead to more serious health outcomes. The American Diabetes Association (ADA) supports routine screening for depression as part of standard diabetes management. The PHQ2 and PHQ9 questionnaires are good diagnostic screening tools used for major depressive disorders in Type 2 diabetes mellitus (DM2). This quality improvement study aims to compare the rate of depression screening, treatment, and referral to behavioral health in adult patients with DM2 pre and post-integration of depression screening tools into the electronic health record (EHR).

Methods We conducted a retrospective chart review on patients …

Efficacy Of Integrating Cbt For Mental Health Care Into Substance Abuse Treatment In Patients With Comorbid Disorders Of Substance Abuse And Mental Illness, Laura U. Madu, Jacqueline Sharp, Bobby Bellflower

Doctor of Nursing Practice Projects

Abstract: Multiple studies have found that psychiatric disorders, like mood disorders and substance use disorders, are highly comorbid among adults with either disorder. Integrated treatment refers to the treatment of two or more conditions and the use of multiple therapies such as the combination of psychotherapy and pharmacotherapy. Integrated therapy for comorbidity per numerous studies has consistently been superior to the treatment of individual disorders separately. The purpose of this QI project was to identify the effectiveness of Cognitive Behavioral Therapy (CBT) instead of current treatment as usual for treating Substance Use Disorder (SUD) or mental health diagnosis independently. It …

The Heme-Regulated Inhibitor Pathway Modulates Susceptibility Of Poor Prognosis B-Lineage Acute Leukemia To Bh3-Mimetics, Kaitlyn Hill Smith

Theses and Dissertations (ETD)

Anti-apoptotic MCL1 is one of the most frequently amplified genes in human cancers and its elevated expression confers resistance to many therapeutics including the BH3-mimetic agents ABT-199 and ABT-263. The anti-malarial, dihydroartemisinin (DHA) translationally represses MCL-1 and synergizes with BH3-mimetics. To explore how DHA represses MCL-1, a genome-wide CRISPR screen identified that loss of genes in the heme synthesis pathway renders mouse BCR-ABL+ B-ALL cells resistant to DHA-induced death. Mechanistically, DHA disrupts the interaction between heme and the eIF2α kinase heme regulated inhibitor (HRI) triggering the integrated stress response. Genetic ablation of Eif2ak1, which encodes HRI, blocks MCL-1 repression in …

Time To First Blood Glucose Determination And Administration Of Intravenous Glucose At Birth In Extremely Low Birth Weight Infants, Jihan Esmail, Ramasubbareddy Dhanireddy Md

Longitudinal Scholar's Project

Background: Extremely low birth weight (ELBW) infants are prone to hypoglycemia unless intravenous glucose is administered within an hour (golden hour) of life. These infants often require resuscitation at birth, but monitoring and intervention for hypoglycemia may be delayed.

Objectives: (1) Study the time to first blood glucose determination and IV glucose administration at birth in ELBW infants, (2) determine the incidence of hypoglycemia, <47mg/dl, and severe hypoglycemia, <40mg/dl, at admission, (3) determine risk factors for hypoglycemia, and (4) compare clinical outcomes at discharge between hypoglycemic and euglycemic infants.

Methods: 244 ELBW (≤1000g birth weight) infants born during Jan 2017- Feb 2020 at the Regional One Health NICU, Memphis, TN were included in the study. Data collected included maternal and infant clinical, demographic, and outcomes …

Hyperglycemia During The First Three Days Of Life Increases The Risk Of Retinopathy Of Prematurity In Extremely Low Birth Weight Infants, Jihan M. Esmail, Ramasubbareddy Dhanireddy Md

Longitudinal Scholar's Project

Background: The association between hyperglycemia and ROP has been inconsistent in previous studies. Extremely low birth weight (ELBW) infants are at high risk for ROP. They also experience hypoglycemia initially and hyperglycemia while receiving IV glucose infusion. The effect of initial hypoglycemia on hyperglycemia associated ROP risk is unknown.

Objective: To study the effect of initial hypoglycemia and subsequent hyperglycemia during the first three days of life on the incidence of ROP and severe ROP in ELBW (birth weight ≤1000g) infants.

Methods: Clinical and demographic data were collected from 227 ELBW infants born during the years 2017-2019 at the Regional …

Genetic Mechanisms Of Transcriptional Regulation In Childhood Acute Lymphoblastic Leukemia, Xujie Zhao

Theses and Dissertations (ETD)

Introduction. Advances in genomic profiling and sequencing studies have identified germline and somatic variations that are associated with childhood ALL, improving our understanding of the genetic basis of childhood acute lymphoblastic leukemia (ALL). Recent genome-wide association studies (GWAS) have identified germline genetic variations of ARID5B and, more recently, IGF2BP1 that are associated with susceptibility to ALL. Genome-wide sequencing studies also discovered a new ALL subtype characterized of ZNF384-mediated chromosomal translocations, providing new insights into genetic heterogeneity in childhood ALL. However, the underlying mechanism by which these genetic variants contribute to the transcriptional regulatory circuitries of ALL is still poorly understood. …

Therapeutic Potential Of Trp Channels In The Targeting Of Rheumatoid Arthritis Synovial Fibroblasts, Brittany Isabella Schwam

Theses and Dissertations (ETD)

Rheumatoid arthritis is a chronic inflammatory disease primarily affecting the synovium, articular cartilage, and bone within a joint, but it is a unique form of arthritis wherein effects are systemic. The cause of this autoimmune disease remains unknown, but there are many environmental and genetic factors that play into susceptibility. Research is still far from drug-free remission despite great advancements over the past few decades. The majority of therapies developed rely on immunosuppressant or immunomodulator molecules and come with risk of infection, high costs, and toxic, uncontrolled side effects. Those diagnosed maintain a significant unmet need for targeted therapies.

There …

Investigating The Role Of Znf384 Rearrangements In Acute Leukemia, Kirsten Dickerson

Theses and Dissertations (ETD)

Chromosomal rearrangements involving ZNF384 are the defining lesion in 5% of pediatric and adult B-cell acute lymphoblastic leukemia and tumors are characterized by aberrant myeloid marker expression. Additionally, ZNF384 rearrangements are the defining lesion in nearly half of pediatric B/myeloid mixed phenotype acute leukemia. These fusions juxtapose full-length ZNF384 to the N terminal portion of a diverse range of partners, most often, transcription factors or epigenetic modifiers. It has been shown that ZNF384-rearranged tumors have a distinct gene expression profile that is consistent between disease groups and N terminal partners. Genomic analyses of patient tumors has shown that ZNF384 fusions …