Medicine and Health Sciences Commons^™

Reframing Medical Education, Herbert L Fred, Jed D Gonzalo

The Texas Heart Institute Journal

No abstract provided.

2018 Dnp Graduate Project Abstracts, Uthealth Cizik School Of Nursing

Doctor of Nursing Practice Projects 2018-2023

The UTHealth Cizik School of Nursing proudly presents the DNP Project abstracts for the 2018 Class of DNP Graduates.

Associations Between Physical Activity, Health-Related Quality Of Life, Regimen Adherence, And Glycemic Control In Jordanian Adolescents With Type 1 Diabetes, Yousef Aljawarneh

Dissertations and Theses (Open Access)

Background: Adolescents with Type 1 Diabetes (T1D) display a greater than two-fold higher risk of developing microvascular and macrovascular complications compared with the non-diabetic population and the risk increases markedly as glycated hemoglobin (HbA1c) increases. The majority of the findings on the associated factors with improved glycemic control are geared toward Western population with a clear lack of studies on Middle Eastern populations.

Purpose: This study aimed to examine the effect of Physical Activity (PA), Health-Related Quality of Life (HRQoL), and regimen adherence on glycemic control in Jordanian adolescents with T1D.

Methods: The study utilized a cross-sectional design. Jordanian adolescents …

Factors Influencing Physical Activity Among Immigrants From South India: A Qualitative Descriptive Study, Jaya Abraham

Dissertations and Theses (Open Access)

Background: In the United States (U.S), the percentage of diabetes and coronary artery diseases is higher among Asian Indian immigrants compared to other ethnic groups. Although research has been useful in describing patterns of physical activity among South Asian groups, very little is known about the factors influencing physical activity among Asian South Indian (ASI) immigrants. There is very limited research performed on the individual, social, cultural and environmental factors influencing physical activity among ASI immigrants.

Purpose: The study purpose was to explore the factors influencing physical activity with the following primary and secondary aims: The primary aim …

Relationships Of Moral Distress Among Interprofessional Icu Teams, Heather Vincent

Dissertations and Theses (Open Access)

Background: Moral distress is the psychological response to knowing the right action required by a healthcare professional but being unable to act upon the right course of action due to internal, external, and institutional constraints.

Purpose: The study investigated: 1. the level of moral distress among interprofessional healthcare providers working in four ICUs of a single academic hospital as measured by the 21-item Moral Distress Scale-Revised (MDS-R), 2. the differences in moral distress among interprofessional healthcare providers based on demographic characteristics and rankings of clinical scenario on the MDS-R.

Method: Descriptive, cross-sectional design using survey methodology.

Outcomes: Significant differences in …

Bridging The Gap Between Food Insecurity And Subsequent Child Body Mass: Mediating Effects Of Dietary Quality And Feeding Styles In Low-Income Hispanic Preschoolers, Nipa Kamdar

Dissertations and Theses (Open Access)

Background: Low-income Hispanic preschoolers face disproportionately high prevalence of food insecurity (FI) and obesity. Consumption of low-cost, energy-dense foods to compensate for FI leads to excess body-mass. FI parents may adopt feeding styles that contribute to decline in children’s dietary quality. Feeding style describes the amount of demandingness (i.e., control of children’s eating) and responsiveness (i.e., warmth used to express demandingness). FI may indirectly contribute to obesity through dietary quality and feeding style.

Purpose: This study investigated: 1. if dietary quality mediated the relationship between food security status (FSS) at Time 1 (T1) and child body-mass at Time 2 (T2), …

Structure Based Drug Design Of High Affinity Kras Inhibitors, Michael Mccarthy

Dissertations and Theses (Open Access)

RAS, one of the most well characterized membrane-associated small GTPases, is a notorious oncogene with >15% of all tumors harboring RAS mutations. When RAS is mutated it becomes constitutively active sending cell growth, survival and proliferation into overdrive, which subsequently leads to cancer. Although, RAS has been aggressively targeted with drug design efforts for more than 30 years an FDA approved direct inhibitor has not yet been developed. There are three isoforms of RAS in cells; HRAS, NRAS and KRAS. We focused on KRAS since it is the most frequently mutated isoform in cancer. To identify novel non-covalent small molecules …

The Role Of Merlin And Apicobasal Polarity In Endometrial Development And Homeostasis, Erin Lopez

Dissertations and Theses (Open Access)

Apicobasal polarity and cell adhesion are necessary for the proper formation and organization of epithelial tissues. Merlin couples cell polarity and adhesion through correct localization of the polarity protein Par3 and maturation of apical junctions. Merlin and Par3 are necessary for the development and homeostasis of highly regenerative tissues like the epidermis. The continual repopulation of the endometrium after each menstrual cycle requires a constant reorganization of cell polarity and adhesion. The endometrium consists of a luminal epithelium that postnatally gives rise to the distinct glandular epithelium. Endometrial glands are necessary to secrete nutrients for the pre-implantation embryo. In addition, …

Psychiatric Impact Of Tuberous Sclerosis Complex And Utilization Of Mental Health Treatment, Kate Mowrey

Dissertations and Theses (Open Access)

Tuberous sclerosis complex (TSC) is a multi-system, neurocutaneous disorder with neuropsychiatric features known as TSC-associated neuropsychiatric disorders (TAND). While 90% of individuals with TSC have some TAND features, only 20% receive treatment, leading to a 70% treatment gap. This study evaluated perception of disease severity, presence of anxiety and depression, as well as the utilization and barriers towards mental health services among adults with TSC. Disease severity had a moderate and low-moderate association with anxiety and depression, respectively. Regardless of past utilization, respondents had a positive outlook towards the use of mental health services with the major barrier being cost.

Characteristics Of Individuals Undergoing Panel Genetic Testing For Primary Brain Tumors, Sarah Azam

Dissertations and Theses (Open Access)

Background. Currently, there are no genetic testing guidelines for patients with a primary brain tumor (PBT). This population is largely understudied in terms of the family history, tumor grade, pathology, and their relation to genetic contribution. Our aim was to describe patient-specific characteristics and family histories across mutation-positive, negative, and variant of uncertain significance (VUS) cohorts based on cancer-panel genetic test results among patients with a PBT.

Methods. Subjects were referred for multi-gene panel testing between March 2012 and June 2016. Clinical data were ascertained from test requisition forms. The incidence of pathogenic mutations (including likely pathogenic) and VUS’s were …

Mechanisms And Targeting Of Neurodevelopmental Regulator Rest In Medulloblastoma Dissemination, Keri Callegari

Dissertations and Theses (Open Access)

Molecular subgrouping of medulloblastoma (MB) has produced four subgroups: wingless (WNT), sonic hedgehog (SHH), group 3, and group 4. While patients with WNT tumors have the best prognosis, patients with SHH tumors have a more variable prognosis concurrent with metastatic disease. This subset of SHH patients have elevated levels of the neurogenic regulator, RE1 Silencing Transcription factor (REST). To understand the role of REST in MB, we utilized a novel transgenic mouse model wherein REST expression can be conditionally elevated during postnatal development in the cells of origin of SHH MB, cerebellar granule neural progenitors (GNPs). While these mice did …

Patient Attitudes To Ward Genetic Testing For Inherited Predispositions To Hematologic Malignancies, Taylor Beecroft

Dissertations and Theses (Open Access)

Although inherited predispositions to hematologic malignancies have previously been considered extremely rare, approximately 12 causative genes have been implicated in the last decade. Since individuals diagnosed with leukemia have not historically been considered for evaluation of inherited predispositions, genetic testing is underperformed in this population. This study used focus group discussions to explore the attitudes, motivations, and barriers to genetic testing for 23 patients with leukemia. Participants generally exhibited a positive regard for the utility of genetic testing, and were primarily motivated by concern for their family and a sense of altruism toward all leukemia patients. While drawbacks and barriers …

Investigating Invasion In Ductal Carcinoma In Situ With To Pographical Single Cell Genome Sequencing, Anna Casasent, Anna Casasent

Dissertations and Theses (Open Access)

Synchronous Ductal Carcinoma in situ (DCIS-IDC) is an early stage breast cancer invasion in which it is possible to delineate genomic evolution during invasion because of the presence of both in situ and invasive regions within the same sample. While laser capture microdissection studies of DCIS-IDC examined the relationship between the paired in situ (DCIS) and invasive (IDC) regions, these studies were either confounded by bulk tissue or limited to a small set of genes or markers. To overcome these challenges, we developed Topographic Single Cell Sequencing (TSCS), which combines laser-catapulting with single cell DNA sequencing to measure genomic copy …

Current Genetic Counseling Practice Following Positive Non-Invasive Prenatal Testing For Sex Chromosome Abnormalities, Lauren Fleddermann

Dissertations and Theses (Open Access)

The purpose of this study was to describe current prenatal and pediatric genetic counseling practice following a non-invasive prenatal testing (NIPT) result positive for a sex chromosome abnormality (SCA). The positive predictive value for SCA with NIPT is lower than seen for Trisomy 21 due to natural loss of the X chromosome from maternal cells during aging, confined placental mosaicism, and undiagnosed maternal sex chromosome abnormality. Except for 45,X, individuals with SCA usually have no ultrasound or postnatal findings. This makes follow-up for unresolved positive NIPT necessary; however, there are currently no clinical guidelines. This study used a prospective anonymous …

Functional Heterogeneity Of Fibroblasts In Dermal Wound Healing, Ehsan Ehsanipour

Dissertations and Theses (Open Access)

Impaired wound healing can lead to excessive scarring, dehiscence, chronic ulcers, and infection, which have adverse impact on the quality of life and pose a significant economic burden on the health care system. Thus, new therapeutic approaches are critically important. Dermal fibroblasts are critical players in cutaneous wound healing, possibly lending their contractile properties and extracellular matrix (ECM) remodeling functions to promote effective tissue repair. Dermal fibroblasts are also postulated to orchestrate tissue repair by interacting with and controlling other cell types in the wound microenvironment. It has become increasingly clear that the generic term “fibroblast” encompasses a diverse cell …

The Epithelial To Mesenchymal Transition In Breast Cancer Induces Alterations In Metabolism, Esmeralda Ramirez-Peña

Dissertations and Theses (Open Access)

Metastasis is currently incurable. Recent studies suggest that metabolic reprogramming significantly impacts metastatic progression. Understanding the underlying biology of how metabolic reprogramming influences metastasis will shed light on developing novel ways to treat metastasis and is of urgent clinical need. A potent mediator of metastatic potential in breast cancer is the winged helix/Forkhead domain transcription factor FOXC2. We have previously shown that FOXC2 is necessary and sufficient to promote metastasis through induction of the epithelial to mesenchymal transition (EMT). EMT is a latent embryonic program that is aberrantly induced in breast cancer cells conferring migratory and invasive capabilities in addition …

Epithelial To Mesenchymal Transition As A Predictor Of Response To Polo-Like Kinase 1 Inhibition-Induced Apoptosis In Non-Small Cell Lung Carcinoma, Pavitra Viswanath

Dissertations and Theses (Open Access)

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. Outcomes are poor for patients with recurrent, advanced or metastatic NSCLC. Polo-like kinase 1 (PLK1), involved in the regulation of mitotic processes and the response to DNA damage, is overexpressed in NSCLC. Inhibiting PLK1 may be an effective treatment for NSCLC patients as it is involved in the mechanisms of resistance to several chemotherapy drugs. PLK1 inhibition or knock-down has various effects in cancer cells, including mitotic arrest, apoptosis, and senescence. Predictive biomarkers have not been identified to select those patients who are likely to respond to …

Investigating The Impact Of Intragenic Dna Methylation On Gene Expression, And The Clinical Implications On Tumor Cells And Associated Stroma, Michael Mcguire

Dissertations and Theses (Open Access)

Investigations into the function of non-promoter DNA methylation have yielded new insights into epigenetic regulation of gene expression. Previous studies have highlighted the importance of distinguishing between DNA methylation in discrete functional regions; however, integrated non-promoter DNA methylation and gene expression analyses across a wide number of tumor types and corresponding normal tissues have not been performed. Through integrated analysis of gene expression and DNA methylation profiles, we uncovered an enrichment of DNA methylation sites within the gene body and 3’UTR in which DNA methylation is strongly positively correlated with gene expression. We examined 32 tumor types and identified 57 …

Development And Characterization Of A Bi-Specific Antibody Targeting Hla-A2/Pr1, Amanda Herrmann

Dissertations and Theses (Open Access)

Despite substantial advances in the treatment of acute myeloid leukemia (AML), only 30% of AML patients survive more than 5 years. Therefore, new therapeutics are much needed. Here, we present novel therapeutic strategy targeting myeloid leukemia antigen, HLA-A2 restricted peptide PR1.Previously, we have conducted pre-clinical development and humanization of a T cell receptor-like monoclonal antibody (h8F4) that targets PR1/HLA-A2 and eliminates AML xenografts by antibody-dependent cellular cytotoxicity (ADCC) following repeat dosing. To improve the potency of h8F4, we have developed a bi-specific T cell-engaging antibody that targets PR1/HLA-A2 on leukemia and CD3 on neighboring T cells. Here we demonstrate successful …

Nanoscale Organization Of The Small Gtpase Rac1, Kelsey Maxwell

Dissertations and Theses (Open Access)

Rac1 is a small, guanine-nucleotide binding protein that cycles between an inactive GDP-bound and active GTP-bound state to regulate actin-mediated motility, migration, and adhesion. Plasma membrane (PM) localization is essential for its biological activity. Rac1 PM targeting is directed by a C-terminal membrane anchor that encompasses a geranylgeranyl-cysteine-methyl-ester, palmitoyl, and a polybasic domain (PBD) of contiguous lysine and arginine residues. Using high-resolution imaging combined with spatial mapping analysis, I found that Rac1 forms nanoclusters on the PM. Cycling between the GTP- and GDP-bound states, Rac1 forms nanoclusters that are non-overlapping, consequently undergoing guanine nucleotide-dependent spatial segregation. I further found that …

Examining The Relationship Between Genetic Counselors’ Implicit Attitudes To Ward Disability And Their Practice Methods, Helen W. Gould

Dissertations and Theses (Open Access)

Genetic counselors serve as a link between the medical community and the disability community as they are regularly the first exposure families have following a new diagnosis in a pregnancy, infant or child. This role requires genetic counselors to be responsible and compassionate when approaching conversations about disability. With a lack of research on how the specific attitudes of genetic counselors toward disability impact clinical practice, we aimed to understand these attitudes, what factors affect implicit attitudes toward disability, and how these attitudes affect counseling. Case scenarios involving disability were used to examine different counseling content preferences within a genetic …

Genetic Testing Practices Of Genetic Counselors, Geneticists, And Pediatric Neurologists With Regard To Childhood-Onset Neurogenetic Conditions, Sara Wofford

Dissertations and Theses (Open Access)

Identifying genetic diagnoses for neurological conditions with a considerable hereditary component, such as autism spectrum disorder (ASD), intellectual disability, and epilepsy, is critical to providing proper medical management for these patients and their families. However, many patients with these conditions are not tested appropriately or receive no genetic testing at all. The current study was designed to characterize the genetic testing practices of the providers most likely to evaluate or order genetic testing for these patients: pediatric neurologists, geneticists, and genetic counselors. The study noted significant variance between the testing strategies selected by pediatric neurologists compared to those of geneticists …

Outcomes Of Genetic Testing In A Genitourinary Genetics Clinic, Annelise Pace

Dissertations and Theses (Open Access)

Several known hereditary cancer syndromes confer an increased risk for genitourinary (GU)related malignancies. Various guidelines indicate when to refer patients to genetic counseling for GU-related hereditary cancer syndromes but there is limited research on the clinical picture of these patients, including their cancerous and non-cancerous features, the genetic testing strategy for this population, and the probability of having a positive germline mutation if testing is performed. The purpose of this study is to determine the most common indications for ordering genetic testing in a GU Genetics Clinic and evaluate whether there is a relationship between the indication for genetic testing …

Identification Of Tissue And Circulating Biomarkers For Premalignant And Malignant Lesions, Shu-Hong Lin

Dissertations and Theses (Open Access)

Recent advancement in technologies including next-generation sequencing and production-scale throughput qPCR have revolutionized the identification of biomarkers in the epidemiology field. In response to the vast amount of data generated from high-throughput technologies, novel inventions in the computer sciences fields have been applied to analyze these data. The current study demonstrates the application of such technologies in a variety of scenarios.

I first described how targeted and whole-exome sequencing were used to identify somatic mutations which marked the differences between colorectal adenomas and adenocarcinomas. A statistical test based on the unique clustering pattern of tumor suppressor genes and oncogenes was …

Computational Insights Into The Generation Of Chromosomal Copy Number Changes, Yihua Liu

Dissertations and Theses (Open Access)

Deviations from a diploid configuration of the human genome, spanning single genes or entire chromosomes, can have wide-ranging impacts on the variation of human phenotypes, including Mendelian and complex forms of diseases. These chromosomal alterations — such as duplications, deletions or copy-neutral loss-of-heterozygosity — are thus important forms of genetic variation for phenotyping populations of individuals as well as populations of cells. Indeed, copy number variants (CNVs) serve as hallmarks of critical changes in the development of particular diseases such as cancer and thus may be used as biomarkers. These CNVs may be either inherited (transmitted by germ cells, originating …

Tumor Immunotherapy: Mechanisms Of Acquired Resistance And Characterization Of Immune Related To Xicities, Ashvin Jaiswal

Dissertations and Theses (Open Access)

Tumor immunotherapy has shown very promising clinical benefit across an array of cancers; however, two major challenges remain unresolved in the field. First, many patients do not respond to therapy at all or relapse after a period of remission. Second, there are often dose-limiting immune related adverse effects associated with immunomodulation.

In order to understand the mechanisms employed by tumors to evade immunotherapeutic responses, we established a murine model of melanoma designed to elucidate the molecular mechanisms underlying immunotherapy resistance. Through multiple in vivo passages, we selected a B16 melanoma tumor line that evolved complete resistance to combination blockade of …

Identifying Subunit Organization And Function Of The Nuclear Rna Exosome Machinery, Jillian Losh

Dissertations and Theses (Open Access)

IDENTIFYING SUBUNIT ORGANIZATION AND FUNCTION OF THE NUCLEAR RNA EXOSOME MACHINERY

Jillian Strother Losh, A.S., B.S.

The eukaryotic RNA exosome processes and degrades many classes of RNA. It is present in the nucleus and the cytoplasm, highly evolutionarily conserved, and essential for viability. Since the RNA exosome is such a significant component of the RNA degradation machinery, it is unsurprising that even single point mutations in a few of its subunits have been linked to human disease. For example, at least eight point mutations in a single subunit of the RNA exosome have been linked to pontocerebellar hypoplasia subtype 1b …

Sphingosine Kinase 1 Regulates Fascin Expression To Promote Metastasis In Triple Negative Breast Cancer, Sunil Acharya

Dissertations and Theses (Open Access)

Distant metastasis is the primary cause of breast cancer–related mortality. To date, effective therapeutic drugs that target metastasis are still lacking. Triple negative breast cancer (TNBC) occurs in high frequency in young women and are more likely to recur and metastasize than are other breast cancer subtypes. Also, TNBC patients cannot benefit from currently available hormonal or targeted therapies, as they lack estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. Thus, understanding the signaling pathways that promote TNBC metastasis and developing novel therapeutic approaches to target them are critical, in order to prolong the survival and improve …

Genomic Evolution Of Chemoresistance In Triple-Negative Breast Cancer Delineated By Single Cell Sequencing, Charissa Kim

Dissertations and Theses (Open Access)

Triple-negative breast cancer (TNBC) is an aggressive subtype that displays extensive intratumor heterogeneity and frequently (46%) develops resistance to neoadjuvant chemotherapy (NAC). Currently, the genomic basis of chemoresistance remains poorly understood. An important question is whether resistance to chemotherapy is driven by the selection of rare pre-existing subclones with genomic mutations and transcriptional programs that confer resistance to chemotherapy (adaptive resistance) or by the spontaneous induction of new mutations and expression changes that confer a resistant phenotype (acquired resistance). To investigate this question we applied single cell DNA and RNA sequencing methods and deep-exome sequencing to longitudinal time-point samples collected …

Somatostatin Receptor 2 Regulation By C-Terminal Motifs And Pdz Domain Proteins, Courtney Olsen

Dissertations and Theses (Open Access)

Somatostatin receptor 2 (sst2) is a Gi-coupled G-protein coupled receptor that mediates many of somatostatin’s neuroendocrine actions. Sst2 is a clinically important GPCR as it is the drug target of somatostatin analogs such as octreotide, lanreotide, and pasireotide. Treatment with these agonists is the main medical approach to controlling excessive hormone secretion from neuroendocrine tumors. Activation of sst2 decreases hormone secretion by inhibiting cAMP production and decreasing intracellular calcium concentrations. In addition, treatment with somatostatin analogs has been shown to decrease tumor growth. Unfortunately, many patients will fail to respond to somatostatin analogs despite sst2 being present on their tumors. …