Medicine and Health Sciences Commons^™

Investigation Of The Roles Of Asf1 And Caf-1-Mediated Chromatin Assembly In The Human Dna Damage Response, Ting-Hsiang Huang

Dissertations and Theses (Open Access)

The access-repair-restore model for the role of chromatin in DNA repair infers that chromatin is a mere obstacle to DNA repair. However, here we show that blocking chromatin assembly of newly-synthesized histones, via knockdown of the histone chaperones ASF1A, CAF-1 or a mutation that specifically prevents ASF1 binding to histones, hinders loading of Rad51 onto ssDNA during homologous recombination, as a consequence of reduced recruitment of the Rad51 loader MMS22L/TONSL to ssDNA, resulting in persistent RPA foci, extensive DNA end-resection, and persistent activation of the ATR-Chk1 pathway. By contrast, ASF1 and CAF-1 render the rapid inactivation of ATM Chk2 pathway …

Developing Novel Approaches To Improve Response To T Cell Based Cancer Immunotherapy, Rina M. Mbofung

Dissertations and Theses (Open Access)

Recently, T cell based immunotherapies have moved to the forefront of cancer immunotherapy with the success of Adoptive T cell therapy (ACT) and Immune checkpoint blockade.ACT, where patients are treated with tumour infiltrating T cells (TILs), conferred a clinical response rate of ~50%. Treatment with anti-CTLA4 and anti –PD1 therapy, conferred response rates of up to 50%, greatly improving the overall survival of patients with advanced melanoma amongst other cancer types. Despite the encouraging outcomes, there are relatively low response rates coupled with the delay of weeks to months before tumour shrinkage can be appreciated. Thus, understanding what tumour intrinsic …

The Utilization Of Prenatal Microarray: A Survey Of Current Genetic Counseling Practices And Barriers, Leslie N. Durham, Leslie Durham

Dissertations and Theses (Open Access)

Chromosomal microarray (CMA) assesses chromosome copy number variants (CNVs) missed by standard karyotyping. The American College of Obstetricians and Gynecologists (ACOG) recommends CMA for all patients with fetuses with an ultrasound anomaly and suggests that it be made available to all women undergoing invasive testing. In order to assess prenatal genetic counselors’ (GCs) practices regarding the utilization of CMA we conducted a survey of their current practices, attitudes, and perceived barriers. Of the 192 respondents, 183 (95%) have incorporated CMA into clinical practice with the majority (64%) believing that the benefits of CMA outweigh the harms. However, only half (52%) …

Statistical Methods For Assessing Structural Change In Human & Microbial Genomes, Xuan Zhu

Dissertations and Theses (Open Access)

Genetic sequencing has been recognized as an effective approach to accurately address biological problems, such as clinical detection of disease, mutation discovery, and targeting specific biomarkers associated with complex diseases. Compared with conventional Sanger sequencing, next-generation sequencing costs much less due to massively parallel high-throughput sequencing. However, due to large numbers of short read sequences, the accuracy of high-throughput sequencing data remains a challenge in that the data obtained from next-generation sequencing often has higher error rates, which may impact downstream genomic analysis. Even if the downstream genomic analysis performs well, the quality of the result will still be impacted …

Characterizing The Source Of Neutrophil Elastase And Proteinase 3 Cross-Presentation In B-Cell Acute Lymphoblastic Leukemia, Selena Carmona

Dissertations and Theses (Open Access)

Discovery of tumor-associated antigens is an important step in designing effective antigen-targeting immunotherapies. PR1 is a nonameric human leukocyte antigen (HLA)-A2 restricted leukemia-associated antigen derived from serine proteases neutrophil elastase (NE) and proteinase 3 (P3). NE and P3 are primarily expressed in cells of myeloid lineage including granulocytes, bone marrow progenitors and myeloid leukemia. Our lab reported that NE and P3 are cross-presented by antigen presenting cells (APCs) and solid tumors, a mechanism whereby exogenous antigens are endocytosed and presented on HLA class I molecules, inducing a cytotoxic T lymphocyte (CTL)-mediated immune response. Therefore, identifying non-myeloid tumors capable of PR1 …

Undergraduate Student Perceptions And Awareness Of Genetic Counseling, Amanda Gerard

Dissertations and Theses (Open Access)

Genetic counseling (GC) is a rapidly expanding field, and the supply of certified genetic counselors is currently unable to keep up with job demand. Research is fairly limited regarding the awareness and perceptions potential genetic counseling program applicants have of the field and what factors most influence their interest in the field. This study aimed to examine some of these topics. The current study includes data collected from 1,389 undergraduate students in the sciences at 23 universities across the United States who were surveyed regarding information related to their awareness, perceptions, knowledge, and interest in GC. Data analysis was performed …

Attitudes Of Clinicians To Wards Cardiac Surgery And Trisomy 18, Meagan Kaulfus

Dissertations and Theses (Open Access)

Trisomy 18 is an autosomal trisomy characterized by minor to major birth defects, severe disabilities, and high rates of pre- and neonatal mortality. Interventions for these infants have traditionally been withheld with focus instead on palliative support. The issues and attitudes surrounding surgical treatment of congenital heart defects, which occur in approximately 90% of infants with trisomy 18, is of our study’s interest as recent literature has indicated that cardiac surgery is being performed and may lead to improved survival compared to palliative care. In this study, the attitudes of clinicians of multiple specialties towards cardiac surgery for infants with …

Peptide Vaccine Formulation Controls The Duration Of Antigen Presentation And Magnitude Of Tumor‐Specific Cd8+ T Cell Response, Hiep Khong

Dissertations and Theses (Open Access)

Despite remarkable progresses in vaccinology, therapeutic cancer vaccines have not achieved their full potential. We previously showed that the duration of antigen presentation critically affected the quantity and quality of T cell response and subsequent anti‐tumor efficacy. Here we describe L‐tyrosine amino acid‐based microparticles as a novel peptide vaccine adjuvant for the induction of tumor‐specific T cells. L‐tyrosine microparticles did not induce inflammasome activation, but instead extended antigen presentation time. The consequent prolongation in antigen presentation translated into prolonged T cell proliferation and superior numbers and anti‐tumor function of vaccination‐induced CD8+ T cells. Indeed, prolonging antigen presentation by repeated injection …

Analysis Of The Biochemical And Cellular Activities Of Substrate Binding By The Molecular Chaperone Hsp110/Sse1, Veronica M. Garcia

Dissertations and Theses (Open Access)

Molecular chaperones ensure protein quality during protein synthesis, delivery, damage repair, and degradation. The ubiquitous and highly conserved molecular chaperone 70-kDa heat-shock proteins (Hsp70s) are essential in maintaining protein homeostasis by cycling through high and low affinity binding of unfolded protein clients to facilitate folding. The Hsp110 class of chaperones are divergent relatives of Hsp70 that are extremely effective in preventing protein aggregation but lack the hallmark folding activity seen in Hsp70s. Hsp110s serve as Hsp70 nucleotide exchange factors (NEF) that facilitate the Hsp70 folding cycle by inducing release of protein substrate from Hsp70, thus recycling the chaperone for a …

Mathematical Modeling Reveals That G2/M Checkpoint Override Creates A Therapeutic Vulnerability In Tsc2-Null Tumors, Hui Ju Hsieh

Dissertations and Theses (Open Access)

Cell cycle checkpoints determine whether cells meet requirements to progress through the next stage. In response to DNA damage, how cells activate checkpoints have been well studied, but little is known about checkpoint deactivation (recovery), which directly impacts on cell fate. In tumor cells, the signaling network has been rewired due to epigenetic and genetic alterations, which result in resistance to the cell cycle control, and thus resistance to chemotherapy or radiation therapy. Therefore, it is critical to identify molecules required for checkpoint recovery or adaptation after DNA damage.

To achieve this goal, we performed a multidisciplinary study combining reverse …

Mathematical Modeling Reveals That G2/M Checkpoint Override Creates A Therapeutic Vulnerability In Tsc2-Null Tumors, Hui-Ju Hsieh

Dissertations and Theses (Open Access)

Cell cycle checkpoints determine whether cells meet requirements to progress through the next stage. In response to DNA damage, how cells activate checkpoints have been well studied, but little is known about checkpoint deactivation (recovery), which directly impacts on cell fate. In tumor cells, the signaling network has been rewired due to epigenetic and genetic alterations, which result in resistance to the cell cycle control, and thus resistance to chemotherapy or radiation therapy. Therefore, it is critical to identify molecules required for checkpoint recovery or adaptation after DNA damage.

To achieve this goal, we performed a multidisciplinary study combining reverse …

The Role Of Adenosine Signaling In Mature Erythrocytes And Erythroid Progenitors, Hong Liu

Dissertations and Theses (Open Access)

Adenosine is a ubiquitous nucleoside in almost all the cells throughout our bodies. It is highly induced particularly under hypoxia or energy depletion conditions. Adenosine functions as a critical ligand, after binding to membrane-associated adenosine receptors, adenosine initiates a downstream signaling cascade and subsequently contributes to functions of nervous system, immune response, vascular function and even metabolism.

Hypoxia is a condition with limited O₂ availability in the whole body or a region of the body. It is a major consequence of many respiratory and cardiovascular diseases, as well as for people living and working at high altitudes or other …

Cd47+ Exosomes Facilitate Effective Targeting Of Oncogenic Kras In Pancreatic Cancer, Sushrut Kamerkar

Dissertations and Theses (Open Access)

Despite the current standard of care, the prognosis for patients with pancreatic ductal adenocarcinoma (PDAC) remains dismal. Genetic analyses of PDAC show that mutations in the GTPase KRAS are encountered in the majority of patients that present with the disease, and are key drivers of cancer initiation, progression and metastasis. However, while it is recognized that the Ras mediated signaling pathway is a key mediator of PDAC progression, a direct and specific targeting of Ras has been elusive. Therefore, due to the indisputable evidence for the causal functional role of RAS in the biology of PDAC, new approaches to specifically …

Targeting Autophagy To Improve Efficacy Of Cdk4/6 Inhibition In Breast Cancer, Smruthi Vijayaraghavan

Dissertations and Theses (Open Access)

Deregulation of the cell cycle machinery is a hallmark of cancer, leading to aberrant proliferation and tumorigenesis. The crucial role of the CDK4/6-Cyclin D pathway has led to the development and FDA approval (palbociclib, ribociclib) of CDK4/6 inhibitors for the treatment of advanced estrogen receptor positive breast cancer. However, three major clinical challenges remain: i) adverse events leading to discontinuation of therapy and ii) lack of reliable biomarkers to identify responsive patients and iii) acquired resistance to CDK4/6 inhibitors. Previous in vitro studies have shown that palbociclib mediated CDK4/6 inhibition induces G1 arrest and senescence in ER+ breast cancer cells, …

Characterization Of The Role Of The Pkm101-Encoded T4ss Outer Membrane Core Complex In Substrate Transfer, Pilus Biogenesis, And Recipient Cell Contact, Jay E. Gordon

Dissertations and Theses (Open Access)

The bacterial type IV secretion systems (T4SS) encoded on the Escherichia coli pKM101 and R388 conjugative plasmids and the Agrobacterium tumefaciens virB operon are composed of 12 subunits arranged in an architecturally similar fashion. Structural studies of the T4SS from R388 (Trw_R388) highlighted the presence of a distinct outer membrane core complex (OMCC) and inner membrane complex (IMC) joined together by a central stalk. This thesis is focused on the development of the pKM101 model system and the role of an OMCC cap region formed by alpha helical antenna projections (AP) found in VirB10 and TraF_pKM101. …

Detecting And Evaluating Therapy Induced Changes In Radiomics Features Measured From Non-Small Cell Lung Cancer To Predict Patient Outcomes, Xenia J. Fave

Dissertations and Theses (Open Access)

The purpose of this study was to investigate whether radiomics features measured from weekly 4-dimensional computed tomography (4DCT) images of non-small cell lung cancers (NSCLC) change during treatment and if those changes are prognostic for patient outcomes or dependent on treatment modality. Radiomics features are quantitative metrics designed to evaluate tumor heterogeneity from routine medical imaging. Features that are prognostic for patient outcome could be used to monitor tumor response and identify high-risk patients for adaptive treatment. This would be especially valuable for NSCLC due to the high prevalence and mortality of this disease.

A novel process was designed to …

Economic Assessment Of A Highly Pathogenic Avian Influenza Outbreak In Washington And Benton Counties In Arkansas, Antonio Beitia

Graduate Theses and Dissertations

Highly Pathogenic Avian Influenza (HPAI) presents a substantial economic risk to the poultry industry. Domesticated fowl contract HPAI initially through exposure, direct or indirect with migratory waterfowl and outbreaks can result in significant economic losses to growers and the poultry industry at large. A HPAI outbreak occurred in Minnesota and Iowa and spread across over 13 other states in 2014 and 2015. This caused an estimated $1.6 billion in losses (CDC, 2016) and led to shortages of eggs and turkeys together with elevated prices (Anni et al. 2005). Even small outbreaks of HPAI inflict substantial damages as USDA-APHIS guidelines necessitate …

Applying A Multidimensional Strategy To Mitigate Lateral Violence In A Small Rural Community Hospital In Western New York, Nicole M. Lewis

Nursing Doctoral

Providing registered nurses with education and strategies to mitigate lateral violence is an evidenced-based method for creating a culture of civility. A descriptive pilot study with registered nurses was conducted on two medical/surgical units at a small rural community hospital. Strategies included a review of organizational policies, a one-day educational retreat for unit managers and registered nurse champions, and an online educational toolkit on lateral violence for the staff nurses on the pilot units.

The Perceptions Of Success Of Latino Nursing School Graduates In The Appalachian Region Of The United States, Barbara M. Rauscher

Electronic Theses and Dissertations

This qualitative narrative descriptive study focused on nine successful Latino nursing school graduates. Five participants were interviewed twice and four participants were interviewed once for a total of fourteen interviews. Participants and their families immigrated from Brazil, Costa Rica, Cuba, and Mexico. Participants attended school in North Carolina, South Carolina, and Tennessee.

Interviews revealed themes of Familism, Empowerment, and Perseverance. Familism was an overriding theme throughout each of the interviews. Participants described family as being their greatest support. They discussed sacrifices made by their families which assisted them in being successful. In addition, they also shared their willingness to make …

The Role Of The Speech-Language Pathologist When Working With Clients Who Are Transgender: A Guide Of Gender Identity And Cultural Competency, Brett Welch

Theses and Dissertations

It is within the scope of practice of a speech-language pathologist to work with a client who is transgender for voice. However, regardless of the setting, a speech-language pathologist is likely to encounter a person who is transgender on their caseload. The American Speech-Language-Hearing Association mandates that all of its members be culturally competent when working with clients from different cultural backgrounds, including those from the lesbian, gay, bisexual, transgender, and queer community.

This thesis pulls from sociological, linguistic, and queer theory literature to provide an in-depth understanding of identity, gender, and transgender identity formation. With this nuanced understanding of …

The Effect Of High Altitude On Central Blood Pressure And Arterial Stiffness, Christopher Boos, Emmanuel Vincent, Adrian Mellor, David Woods, Caroline Newman, Richard Cruttenden, Matt Barlow, Mark Cooke, Kevin Deighton, Peter Scott, Sarah B. Clarke, John O'Hara

Journal Articles

No abstract provided.

An Investigation Of The Relationship Between Child, Family, And Community Factors And Early Childhood Oral Health And The Utilization Of Dental Health Services, Nicole Holt

Electronic Theses and Dissertations

Background / Objective: Children under the age of 5 years bear a disproportionate burden of oral disease. The aim of this study is to investigate how child, family, and community determinants impact dental care utilization, and parental report of child’s oral health. Methods: Data for this study came from the 2011/2012 National Survey of Children’s Health for children aged 1 to 5 years old. Dependent variables evaluated were if the child had an oral health problem, been to a dentist in the past year, and parents description of the child’s teeth. Independent variables were selected from child, family, and community …

May 2017, Swosu Bulldog Wellness Committee

SWOSU BULLDOG WELLNESS

No abstract provided.

Comparison Of Enteral Versus Intravenous Potassium Supplementation In Hypokalaemia In Paediatric Patients In Intensive Care Post Cardiac Surgery: Open-Label Randomised Equivalence Trial (Eips), Naveed Ur Rehman Siddiqui, Quratulain Merchant, Babar Hasan, Arjumand Rizvi, Muneer M Amanullah, Amina Rehmat, Anwarul Haque

Department of Surgery Docs

Objectives: The primary objective was to compare the efficacy of enteral potassium replacement (EPR) and intravenous potassium replacement (IVPR) as first-line therapy. Secondary objectives included comparison of adverse effects and number of doses required to resolve the episode of hypokalaemia.|
Trial design: The EIPS trial is designed as a randomised, equivalence trial between two treatment arms.
Study setting: The study was conducted at the paediatric cardiac intensive care unit (PCICU) at Aga Khan University Hospital, Karachi.
Participants: 41 patients (aged 1 month to 15years) who were admitted to PCICU post cardiac surgery were recruited (23 IVPR arm and 18 …

Synthesis And In-Vitro Cell Viability/Cytotoxicity Studies Of Novel Pyrrolobenzodiazepine Derivatives, John M. Jarrett

Undergraduate Honors Theses

Pyrrolobenzodiazepines (PBDs) are a group of naturally occurring compounds that were discovered in the cultures of Streptomyces in the 1960s. Some natural PBDs discovered in these cultures, such as anthramycin and sibiromycin, were shown to possess a broad spectrum of anti-tumor activity. Since cancer is still a leading cause of death globally, the development of novel anti-proliferative derivatives of PBDs is essential for human welfare worldwide. Further synthesis and structure-activity relationship (SAR) studies of the parent natural products and their tetracyclic analogs will lead to the discovery of drug candidates. In this work, thirteen PBD analogues were synthesized using no …

Salmonella And Aeromonas Contamination In A 303(D) Listed Water Body Compared To Fecal Indicators & Water Quality Parameters, Elizabeth M. Morgan Ms.

Undergraduate Honors Theses

Since the passage of the Clean Water Act, concern about surface water quality has increased. Reducing exposure to pathogens and adverse impacts on human health because of contact with surface waters has become the focus of many regulatory agencies. Fecal pollution is often a cause of surface water impairment. Fecal indicators, such as fecal coliforms and Escherichia coli, are used as surrogates to evaluate the presence or absence of fecal pollution. However, a growing body of research has shown that these species lack key characteristics necessary to be adequate indicators. As such, explorations into the efficacy of indicator species …

Dental Disparities And The Safety Net In Blount County, Micaela J. Cornett

Undergraduate Honors Theses

This qualitative study focused on the dental disparities in Blount County, TN and sought to determine if there are enough dental clinics within the dental safety net. Interviews were conducted with 18 individuals who were either service providers or clients of organizations such as the Salvation Army, Alcoa Good Samaritan Clinic, the local health department, Trinity Dental Clinic, Volunteer Ministry Center, Remote Area Medical, and Blount Memorial Hospital. Inclusion criteria for clients included: homeless or living below the poverty level, uninsured, 18 to 65 years of age, has not seen a dentist in the past year and currently suffering a …

Long-Term Sustainment Of Rapid Improvement Events: A Case Study In “Room Readiness”, Gabriela V. Coronel

Undergraduate Honors Theses

Shifting payment models from fee for service (FFS) to pay for performance (P4P) have fundamentally changed the environment of healthcare administration in the United States (Center for Medicaid and Medicare Services (CMS), 2011). Due to this shift, there has been an increase in demand for tracking and improving quality measures to ensure not only patient safety, but optimization of utilization. Constraints on resources and capacity, coupled with increasing safety measures has developed a new study of patient flow (Miró, Sánchez, Espinosa, et al., 2003). Decreasing patient room turnover times has the potential to maximize utilization while ensuring patient safety and …

Social Support For Physical Activity For High Schoolers In Rural Appalachia, Pooja M. Shah

Undergraduate Honors Theses

The purpose of the present study is to conduct a secondary qualitative analysis to examine parent, teacher, and high school adolescents’ perceptions of social support for physical activity (PA) for high schoolers in Southern Appalachia. Social support for PA is linked to higher rates of PA participation in adolescents. Parents, siblings, and peers provide key sources of support. Social support for PA may be even more important in under-resourced communities such as Appalachia, where geographic, economic, and environmental barriers negatively impact PA engagement. During 2013-2014, focus groups and semi-structured interviews were conducted with parents of adolescents (n=39), high school teachers …

Perceptions Of Male Nursing Students About Working In Women’S Health, Jose Mari Lawrence Mitra

Undergraduate Honors Theses

This study explores the opinions and experiences of East Tennessee State University (ETSU) male nursing students after they have completed their clinical rotations in obstetrics (OB). Participants are interviewed about their preconceptions and post-experience perspectives regarding the clinical rotation. After analyzing the interviews, the students’ perceptions appeared to be grounded in their perceived level of comfort with women’s health nursing. Themes include (1) preconceptions, (2) welcoming, (3) rejecting, and (4) culture.