Medicine and Health Sciences Commons^™

Molecular Cause And Functional Impact Of Altered Synaptic Lipid Signaling Due To A Prg-1 Gene Snp, Johannes Vogt, Jenq-Wei Yang, Arian Mobascher, Jin Cheng, Yunbo Li, Xingfeng Liu, Jan Baumgart, Carine Thalman, Sergei Kirischuk, Petr Unichenko, Guilherme Horta, Konstantin Radyushkin, Albrecht Stroh, Sebastian Richers, Nassim Sahragard, Ute Distler, Stefan Tenzer, Lianyong Qiao, Klaus Lieb, Oliver Tüscher, Harald Binder, Nerea Ferreiros, Irmgard Tegeder, Andrew J. Morris, Sergiu Gropa, Peter Nürnberg, Mohammad R. Toliat, Georg Winterer, Heiko J. Luhmann, Jisen Huai, Robert Nitsch

Gill Heart & Vascular Institute Faculty Publications

Loss of plasticity‐related gene 1 (PRG‐1), which regulates synaptic phospholipid signaling, leads to hyperexcitability via increased glutamate release altering excitation/inhibition (E/I) balance in cortical networks. A recently reported SNP in prg‐1 (R345T/mutPRG‐1) affects ~5 million European and US citizens in a monoallelic variant. Our studies show that this mutation leads to a loss‐of‐PRG‐1 function at the synapse due to its inability to control lysophosphatidic acid (LPA) levels via a cellular uptake mechanism which appears to depend on proper glycosylation altered by this SNP. PRG‐1^+/− mice, which are animal correlates of human PRG‐1^+/mut carriers, showed an altered cortical network …

Effect Of Enteral Feeding Timing In Septic Shock Patients, Shane D. Slone

DNP Projects

The goal of this research project was to identify the effect of the timing of enteral nutrition (EN) initiation timing on in-hospital mortality, ICU LOS and hospital LOS among patients with septic shock requiring norepinephrine. The study design was a cross-sectional analysis of retrospective electronic health record data. Patients who had received norepinephrine for septic shock were divided into early EN initiation (within 48 hours of ICU admission) and late EN initiation (Greater than or equal to 48 hours after ICU admission) groups. 680 subjects were included; 469 in the early group and 211 in the late group. Demographics, comorbidities, …

Documentation Of Smoking History And Adherence To The Uspstf Recommendation For Lung Cancer Screening: A Retrospective Chart Review, Laura A. Golden

DNP Projects

Purpose: The purpose of this project was to evaluate provider compliance with documentation of smoking history and, if criteria met, referral for lung cancer screening as recommended by the United States Preventive Services Task Force in 2013.

Methods: A retrospective chart review was conducted using an electronic medical record (EMR) at a large, rural community family practice clinic. Patients meeting inclusion criteria of having a smoking history (current or past) of 30 pack years, aged 55 to 80 years, and no history of lung cancer diagnosis were included for randomization. One hundred patients were selected from 300 randomized charts; five …

Baseline Of Copd Management In A Norton Healthcare Primary Care Clinic, Angela Goldring

DNP Projects

Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of death in the United States (U.S), with rates in Kentucky among the highest in the nation. Quality care in the primary care setting is key to optimizing the health outcomes of those with COPD.

Purpose: The objective of this study was to establish a baseline of COPD patient care in a primary care clinic. The specific aims of this study were to: 1) describe the demographic and health-related characteristics of patients with COPD who have a primary care provider (PCP) at one Norton Healthcare primary care clinic; 2) …

Evaluating Adherence To Colorectal Cancer Screening, Jaime Bradley-Miller

DNP Projects

Purpose: The purpose of this project and literature review was to determine provider documentation practices of colorectal cancer (CRC) screening, identify the percent of clinic patients who need to be screened, and develop a set of recommendations and targeted interventions which will increase CRC screening rates.

Methods: A retrospective chart review including males and females of all ethnicities between the ages of 45 and 80 was performed in one primary care practice. A randomized sample of 360 office visits between February and November of 2015 were selected, of which 281 met the inclusion and exclusion criteria. Patient demographics and characteristics …

Co-Morbid Symptoms Of Depression And Anxiety And Bio-Behavioral Response To Stress In Patients With Heart Failure, Abdullah S. Alhurani

Theses and Dissertations--Nursing

Heart failure (HF) is a major public health problem throughout the world. It accounts for one death certificate among nine in the United States. Heart failure and sudden death combined are responsible for the largest number of deaths in America. The total costs of HF in the United States are estimated to be $37 billion each year. Despite substantial medical and surgical advances related to treatment of HF, it remains a very costly condition with high mortality and morbidity rates. Although biological factors contribute to high morbidity and mortality in HF, there are many unexplored psychosocial factors that also likely …

Development And Application Of Gadolinium Free Cardiac Magnetic Resonance Fibrosis Imaging For Multiscale Study Of Heart Failure In Patients With End Stage Renal Disease, Tori A. Stromp

Theses and Dissertations--Physiology

Cardiac magnetic resonance (CMR) is a powerful tool to noninvasively image ventricular fibrosis. Late gadolinium enhancement (LGE) CMR identifies focal and, with T1 mapping, diffuse fibrosis. Despite prevalent cardiac fibrosis and heart failure, patients with end stage renal disease (ESRD) are excluded from LGE. Absence of a suitable diagnostic has limited the understanding of heart failure and obstructed development of therapies in the setting of ESRD. A quantitative, gadolinium free fibrosis detection method could overcome this critical barrier, propelling the advancement of diagnostic, monitoring, and therapy options. This project describes the development of a gadolinium free CMR technique and application …

Regulation Of Uv-Protective Pathways Downstream Of The Melanocortin 1 Receptor In Melanocytes, Erin M. Wolf Horrell

Theses and Dissertations--Physiology

Malignant cutaneous melanoma is the deadliest form of skin cancer, and a majority of melanoma diagnoses are a result of exposure to ultraviolet (UV) radiation. UV radiation causes DNA damage, which if not repaired correctly via nucleotide excision repair (NER) can result in mutations and melanomagenesis. The melanocortin 1 receptor (MC1R) is a G_s protein coupled receptor located on melanocyte plasma membranes and is involved in protecting the skin from UV induced damage. MC1R signaling results in the activation of two protective pathways: 1) induction of eumelanin synthesis downstream of micropthalmia-associated transcription factor (MITF) and 2) acceleration of NER …

Evaluation Of A Diabetes Self-Management Program For Hispanics In Lexington Kentucky: A Pilot Study, Miguel A. Gamboa Oropeza

Theses and Dissertations--Nutrition and Food Systems

Hispanics are more affected by diabetes than non-Hispanic whites and they tend to experience more severe complications. Research shows that although self-management is poor among ethnic minorities, it is even more so among Hispanics. The “Taking Ownership of Your Diabetes” (TOYD) program has been shown to be successful in helping individuals manage their diabetes. However, no work has been conducted with Hispanic audiences in Kentucky. TOYD program allows individuals to modify lifestyle risks and solve problems related to diabetes management. The program was translated from English to Spanish. Hispanics males and females between ages 19 to 75 years …

Assessment Of Obesity Management In A Primary Care Setting, Katie Diffenderfer

DNP Projects

Purpose: The purpose of this study was to evaluate the current practices related to obesity in the primary care setting in University of Kentucky’s Healthcare System. The specific aims were to: 1) Determine the proportion of obese patients who had an ICD-9/10 diagnosis code for obesity, 2) Determine the proportion of obese patients who received interventions related to their obesity, 3) Determine whether obesity diagnosis and interventions varied based on patient demographics, and 4) Compare actual obesity interventions to those outlined in the clinical practice guidelines.

Methods: A retrospective chart review of male and female patients between the ages of …

Investigating The Efficacy Of Vocal Function Exercises In Improving Vocal Function In Adults Irradiated For Laryngeal Cancers: A Three Part Dissertation, Vrushali Angadi

Theses and Dissertations--Rehabilitation Sciences

Deterioration in voice quality following radiation therapy for the treatment of laryngeal cancers (LC) is well documented in literature. The majority of studies show that these voice problems are long term and in some cases permanent. Deterioration in voice quality, especially over a period of time could lead to significant communication difficulties in daily life or in some cases could even result in loss of profession. Despite the negative effects of radiation therapy on voice quality being well documented, few studies have focused on the efficacy of voice therapy in the irradiated LC population.

The purpose of this study was …

Looking To The Future Of Stroke Treatment: Combining Recanalization And Neuroprotection In Acute Ischemic Stroke, Michael E. Maniskas

Theses and Dissertations--Neuroscience

Stroke is the 5^th leading cause of death in the U.S. with 130,000 deaths and around 800,000 affected annually. Currently, there is a significant disconnect between basic stroke research and clinical stroke therapeutic needs. Few animal models of stroke target the large vessels that produce cortical deficits seen in the clinical setting. Also, current routes of drug administration, intraperitoneal and intravenous, do not mimic the clinical route of intra-arterial drug administration. To bridge this divide, we have retro-engineered a mouse model of stroke from the current standard of care for emergent large vessel occlusion (ELVO) stroke, endovascular thrombectomy, to …

Overcoming Treatment Resistance In Heterogeneous Tumors, Nikhil Hebbar

Theses and Dissertations--Toxicology and Cancer Biology

Most primary tumors are heterogeneous and are often composed of therapy-sensitive and emerging therapy-resistant cancer cells. Rather unexpectedly, treatment of therapy-sensitive tumor cells in heterogeneous tumor microenvironments resulted in apoptosis of the therapy-resistant cancer cells. We identified a novel Par-4 amino-terminal fragment (PAF, which includes amino acids 1-131 of Par-4) that is produced and released by therapy-sensitive cancer cells following therapy-induced caspase-dependent cleavage of the tumor suppressor Par-4. PAF caused paracrine apoptosis in therapy-resistant cancer cells. Unlike Par-4-inducible apoptosis, which is dependent on the cell surface GRP78 receptor, PAF produced cancer-selective apoptosis independent of cell surface GRP78 function. Par-4 contains …