Medicine and Health Sciences Commons^™

Arylquinoline And Analog Compounds And Use Thereof To Treat Cancer, David S. Watt, Chunming Liu, Vivek M. Rangnekar, Vitaliy M. Sviripa, Ravshan Burikhanov, Wen Zhang

Molecular and Cellular Biochemistry Faculty Patents

The subject technology relates to arylquinoline compounds and their use for treating cancer or cancer metastasis. The compounds of the subject technology promote cells to secrete a pro-apoptotic tumor suppressor, i.e., prostate apoptosis response-4 (Par-4), which in turn promote apoptosis in cancer cells or metastatic cells.

Management Of Aortic Insufficiency In Patients With Left Ventricular Assist Device ̶ A Retrospective Analysis, Hartmuth B. Bittner

The VAD Journal

Background: Aortic insufficiency is increasingly recognized as a complication of left ventricular assist device (LVAD) support and may lead to clinical decompensation requiring correction. This article describes experiences in managing patients presenting with concomitant aortic insufficiency and with de novo aortic insufficiency following left ventricular assist device implantations.

Methods: All patients undergoing LVAD implantation between 2012 and 2014 were included in this retrospective analysis if aortic valve insufficiency was present on implantation or newly developed (de novo) after implantation. Moderate to severe aortic valve insufficiency was corrected at implantation.

Results: The data of 39 patients were included. At the time …

Dynamic Cycling Of T-Snare Acylation Regulates Platelet Exocytosis, Jinchao Zhang, Yunjie Huang, Jing Chen, Haining Zhu, Sidney W. Whiteheart

Molecular and Cellular Biochemistry Faculty Publications

Platelets regulate vascular integrity by secreting a host of molecules that promote hemostasis and its sequelae. Given the importance of platelet exocytosis, it is critical to understand how it is controlled. The t-SNAREs, SNAP-23 and syntaxin-11, lack classical transmembrane domains (TMDs), yet both are associated with platelet membranes and redistributed into cholesterol-dependent lipid rafts when platelets are activated. Using metabolic labeling and hydroxylamine (HA)/HCl treatment, we showed that both contain thioester-linked acyl groups. Mass spectrometry mapping further showed that syntaxin-11 was modified on cysteine 275, 279, 280, 282, 283, and 285, and SNAP-23 was modified on cysteine 79, 80, 83, …

The Rewarding Nature Of Provocation-Focused Rumination In Women With Borderline Personality Disorder: A Preliminary Fmri Investigation, Jessica R. Peters, David S. Chester, Erin C. Walsh, C. Nathan Dewall, Ruth A. Baer

Psychology Faculty Publications

Background: Understanding why individuals with borderline personality disorder (BPD) ruminate on prior provocations, despite its negative outcomes, is crucial to improving interventions. Provocation-focused rumination may be rewarding in the short term by amplifying anger and producing feelings of justification, validation, and increased energy, while reducing self-directed negative affect. If provocation-focused rumination is utilized regularly as a rewarding emotion regulation strategy, it could result in increased activation in reward-related neural regions. The present pilot study examined neural correlates of provocation-focused rumination, relative to other forms of thought, in BPD.

Method: Functional magnetic resonance imaging (fMRI) was utilized to examine this theory …

Peri-Implant Behavior Of Sloped Shoulder Dental Implants Used For All-On-Four Protocols: An Histomorphometric Analysis In Dogs, Jose Luis Calvo Guirado, Aldo Fabian Lucero-Sánchez, Ana Boquete Castro, Marcus Abboud, Sergio Gehrke, Manuel Fernández Dominguez, Rafael Arcesio Delgado Ruiz

Digital Dentistry Faculty Publications

Abstract: The aim of this study was to evaluate the soft tissue thickness and marginal bone loss around dental implants with sloped micro-threaded shoulder (30° angle) in comparing with conventional design, inserted 30° degrees angulated in post extraction sockets and immediate loaded with temporary prosthesis simulating the all-on-four protocol. Materials and Methods: Six fox hound dogs received forty-eight post extraction dental implants with the different diameter and length (Medentika, Germany), but with different neck configurations. Two group of implants were inserted 1mm subcrestal. Control group has a micro-threaded neck and the Test group has a sloped microthreaded neck. Immediate loading …

Beta-Catenin Cleavage Enhances Transcriptional Activation, Tatiana Goretsky, Emily M. Bradford, Qing Ye, Olivia F. Lamping, Tomas Vanagunas, Mary Pat Moyer, Patrick C. Keller, Preetika Sinh, Josep M. Llovet, Tianyan Gao, Qing-Bai She, Linheng Li, Terrence A. Barrett

Internal Medicine Faculty Publications

Nuclear activation of Wnt/β-catenin signaling is required for cell proliferation in inflammation and cancer. Studies from our group indicate that β-catenin activation in colitis and colorectal cancer (CRC) correlates with increased nuclear levels of β-catenin phosphorylated at serine 552 (pβ-Cat⁵⁵²). Biochemical analysis of nuclear extracts from cancer biopsies revealed the existence of low molecular weight (LMW) pβ-Cat⁵⁵², increased to the exclusion of full size (FS) forms of β-catenin. LMW β-catenin lacks both termini, leaving residues in the armadillo repeat intact. Further experiments showed that TCF4 predominantly binds LMW pβ-Cat⁵⁵² in the nucleus of inflamed and …

Phylogenetic Analysis And Characterization Of A Sporadic Isolate Of Equine Influenza A H3n8 From An Unvaccinated Horse In 2015, Chithra C. Sreenivasan, Sunayana S. Jandhyala, Sisi Luo, Ben M. Hause, Milton Thomas, David E. B. Knudsen, Pamela Leslie-Steen, Travis Clement, Stephanie E. Reedy, Thomas Chambers, Jane Christopher-Hennings, Eric Nelson, Dan Wang, Radhey S. Kaushik, Feng Li

Maxwell H. Gluck Equine Research Center Faculty Publications

Equine influenza, caused by the H3N8 subtype, is a highly contagious respiratory disease affecting equid populations worldwide and has led to serious epidemics and transboundary pandemics. This study describes the phylogenetic characterization and replication kinetics of recently-isolated H3N8 virus from a nasal swab obtained from a sporadic case of natural infection in an unvaccinated horse from Montana, USA. The nasal swab tested positive for equine influenza by Real-Time Quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR). Further, the whole genome sequencing of the virus confirmed that it was the H3N8 subtype and was designated as A/equine/Montana/9564-1/2015 (H3N8). A BLASTn search revealed …

Internal Carotid Artery Stenosis: A Novel Surgical Model For Moyamoya Syndrome, Jill M. Roberts, Michael E. Maniskas, Justin F. Fraser, Gregory J. Bix

Sanders-Brown Center on Aging Faculty Publications

Moyamoya is a cerebrovascular disorder characterized by progressive stenosis of the intracranial internal carotid arteries. There are two forms: Disease and Syndrome, with each characterized by the sub-population it affects. Moyamoya syndrome (MMS) is more prominent in adults in their 20’s-40’s, and is often associated with autoimmune diseases. Currently, there are no surgical models for inducing moyamoya syndrome, so our aim was to develop a new animal model to study this relatively unknown cerebrovascular disease. Here, we demonstrate a new surgical technique termed internal carotid artery stenosis (ICAS), to mimic MMS using micro-coils on the proximal ICA. We tested for …

Peripheral Quantitative Computed Tomography Detects Differences At The Radius In Prepubertal Children With Cystic Fibrosis Compared To Healthy Controls, Catherine E. O'Brien, Gulnur Com, John L. Fowlkes, Xinyu Tang, Laura P. James

Barnstable Brown Diabetes Center Faculty Publications

Introduction

In 2015, 11.9% of people with cystic fibrosis (CF) in the United States had osteopenia, 5.1% osteoporosis, and 0.3% experienced a fracture. Screening for CF-related bone disease starts in childhood, and dual energy x-ray absorptiometry (DXA) is the recommended method. It is unknown whether peripheral quantitative computed tomography (pQCT) can detect deficits earlier than DXA. This study compared pQCT and DXA scans in a group of pre-pubertal children with CF and healthy controls.

Methods

This was a cross-sectional study of children at Tanner stage 1. A pQCT scan of the radius at proximal and distal sites was performed plus …

Inhibition Of Dihydrotestosterone Synthesis In Prostate Cancer By Combined Frontdoor And Backdoor Pathway Blockade, Michael V. Fiandalo, John J. Stocking, Elena A. Pop, John H. Wilton, Krystin M. Mantione, Yun Li, Kristopher M. Attwood, Gissou Azabdaftari, Yue Wu, David S. Watt, Elizabeth M. Wilson, James L. Mohler

Center for Pharmaceutical Research and Innovation Faculty Publications

Androgen deprivation therapy (ADT) is palliative and prostate cancer (CaP) recurs as lethal castration-recurrent/resistant CaP (CRPC). One mechanism that provides CaP resistance to ADT is primary backdoor androgen metabolism, which uses up to four 3α-oxidoreductases to convert 5α-androstane-3α,17β-diol (DIOL) to dihydrotestosterone (DHT). The goal was to determine whether inhibition of 3α-oxidoreductase activity decreased conversion of DIOL to DHT. Protein sequence analysis showed that the four 3α-oxidoreductases have identical catalytic amino acid residues. Mass spectrometry data showed combined treatment using catalytically inactive 3α-oxidoreductase mutants and the 5α-reductase inhibitor, dutasteride, decreased DHT levels in CaP cells better than dutasteride alone. Combined blockade …

Novel Function Of Ceramide For Regulation Of Mitochondrial Atp Release In Astrocytes, Ji-Na Kong, Zhihui Zhu, Yutaka Itokazu, Guanghu Wang, Michael B. Dinkins, Liansheng Zhong, Hsuan-Pei Lin, Ahmed Elsherbini, Silvia Leanhart, Xue Jiang, Haiyan Qin, Wenbo Zhi, Stefka D. Spassieva, Erhard Bieberich

Physiology Faculty Publications

We reported that amyloid β peptide (Aβ₄₂) activated neutral SMase 2 (nSMase2), thereby increasing the concentration of the sphingolipid ceramide in astrocytes. Here, we show that Aβ₄₂ induced mitochondrial fragmentation in wild-type astrocytes, but not in nSMase2-deficient cells or astrocytes treated with fumonisin B1 (FB1), an inhibitor of ceramide synthases. Unexpectedly, ceramide depletion was concurrent with rapid movements of mitochondria, indicating an unknown function of ceramide for mitochondria. Using immunocytochemistry and super-resolution microscopy, we detected ceramide-enriched and mitochondria-associated membranes (CEMAMs) that were codistributed with microtubules. Interaction of ceramide with tubulin was confirmed by cross-linking to N-[9-(3-pent-4-ynyl-3-H-diazirine-3-yl)-nonanoyl]-D-erythro-sphingosine …

A Plasma Telomeric Cell-Free Dna Level In Unaffected Women With Brca1 Or/And Brca2 Mutations: A Pilot Study, Shatovisha Dey, Natascia Marino, Kanokwan Bishop, Paige N. Dahlgren, Aditi Shendre, Anna Maria Storniolo, Chunyan He, Hiromi Tanaka

Internal Medicine Faculty Publications

Plasma cell-free DNA (cfDNA) is a small DNA fragment circulating in the bloodstream originating from both non-tumor- and tumor-derived cells. A previous study showed that a plasma telomeric cfDNA level decreases in sporadic breast cancer patients compared to controls. Tumor suppressor gene products including BRCA1 and BRCA2 (BRCA1&2) play an important role in telomere maintenance. In this study, we hypothesized that the plasma telomeric cfDNA level is associated with the mutation status of BRCA1&2 genes. To test this hypothesis, we performed plasma telomeric cfDNA quantitative PCR (qPCR)-based assays to compare 28 women carriers of the BRCA1&2 mutation with age-matched controls …

Approach To Unresponsive Patient With Lvad, Maya Guglin

The VAD Journal

No abstract provided.

The Application Of An Implementation Science Framework To Comprehensive School Physical Activity Programs: Be A Champion!, Justin B. Moore, Russell L. Carson, Collin A. Webster, Camelia R. Singletary, Darla M. Castelli, Russell R. Pate, Michael W. Beets, Aaron Beighle

Kinesiology and Health Promotion Faculty Publications

Comprehensive school physical activity programs (CSPAPs) have been endorsed as a promising strategy to increase youth physical activity (PA) in school settings. A CSPAP is a five-component approach, which includes opportunities before, during, and after school for PA. Extensive resources are available to public health practitioners and school officials regarding what should be implemented, but little guidance and few resources are available regarding how to effectively implement a CSPAP. Implementation science provides a number of conceptual frameworks that can guide implementation of a CSPAP, but few published studies have employed an implementation science framework to a CSPAP. Therefore, we developed …

An Intracellular Activation Of Smoothened That Is Independent Of Hedgehog Stimulation In Drosophila, Kai Jiang, Yajuan Liu, Jie Zhang, Jianhang Jia

Markey Cancer Center Faculty Publications

Smoothened (Smo), a GPCR family protein, plays a critical role in the reception and transduction of Hedgehog (Hh) signal. Smo is phosphorylated and activated on the cell surface; however, it is unknown whether Smo can be intracellularly activated. Here, we demonstrate that inactivation of the ESCRT-III causes dramatic accumulation of Smo in the ESCRT-III/MVB compartment, and subsequent activation of Hh signaling. In contrast, inactivation of ESCRTs 0–II induces mild Smo accumulation in the ESCRT-III/MVB compartment. We provide evidence that Kurtz (Krz), the Drosophila β-arrestin2, acts in parallel with the ESCRTs 0-II pathway to sort Smo to the multivesicular bodies and …

Unresponsive Patient With Lvad: A Case Series, Ameer Z. Musa, Julia Akhtarekhavari

The VAD Journal

Mechanical circulatory support (MCS) for patients with advanced heart failure (HF) is becoming more commonplace as technology has progressed and reliability of these systems has improved. We report our experience with three patients with cardiopulmonary arrest in the hospital and propose a protocol for the prompt assessment and treatment of an unresponsive patient with a LVAD in place. We presented three cases of unresponsive patients on LVAD support with low flow or no flow through the LVAD. Although all three of them were alive after resuscitation, none survived to discharge. In all three cases, there were no flaws in LVAD …

Antagonistic Actions Of Juvenile Hormone And 20-Hydroxyecdysone Within The Ring Gland Determine Developmental Transitions In Drosophila, Suning Liu, Kang Li, Yue Gao, Xi Liu, Weiting Chen, Wei Ge, Qili Feng, Subba Reddy Palli, Sheng Li

Entomology Faculty Publications

In both vertebrates and insects, developmental transition from the juvenile stage to adulthood is regulated by steroid hormones. In insects, the steroid hormone, 20-hydroxyecdysone (20E), elicits metamorphosis, thus promoting this transition, while the sesquiterpenoid juvenile hormone (JH) antagonizes 20E signaling to prevent precocious metamorphosis during the larval stages. However, not much is known about the mechanisms involved in cross-talk between these two hormones. In this study, we discovered that in the ring gland (RG) of Drosophila larvae, JH and 20E control each other’s biosynthesis. JH induces expression of a Krüppel-like transcription factor gene Kr-h1 in the prothoracic gland (PG), a …

Exploring Evolutionary Medicine Through 19Th Century Medical Collections: Applications In Archival Studies, Taylor Sturgill

Special Collections Research Center Learning Lab Student Research

Evolution has been a paradox in the field of science, but, the study of evolutionary medicine applies both the evolutionary game theory and medicine. This study was conducted to explore evolution by analyzing two 19th century collections of medical formulations and prescriptions while compared to the trend of public health and pathogenic mechanisms. Analysis of organic structure in historical prescriptions, descriptive epidemiology in Kentucky, and the idea of the germ theory will be used explicitly to show the evolutionary change of health and disease. Results of this study provided an outlook on ingredients that stimulate the body as a whole …

Impact Of Air Manganese On Child Neurodevelopment In East Liverpool, Ohio, Erin N. Haynes, Heidi Sucharew, Timothy J. Hilbert, Pierce Kuhnell, Alonzo Spencer, Nicholas C. Newman, Roxanne Burns, Robert Wright, Patrick J. Parsons, Kim N. Dietrich

Epidemiology and Environmental Health Faculty Publications

Background: East Liverpool, Ohio, the site of a hazardous waste incinerator and a manganese (Mn) processor, has had air Mn concentrations exceeding United States Environmental Protection Agency reference levels for over a decade. Save Our County, Inc., a community organization, was formed to address community environmental health concerns related to local industry. Researchers from the University of Cincinnati partnered with Save Our County to determine if air Mn had an impact on the neurocognitive function of children in the community.

Methods: Children 7–9 years of age from East Liverpool and its surrounding communities, were enrolled (N = 106) in the …

Missed Work Due To Occupational Illness Among Hispanic Horse Workers, Ashley M. Bush, Susan C. Westneat, Steven R. Browning, Jennifer Swanberg

Kentucky Injury Prevention and Research Center Faculty Publications

Occupational illnesses are inadequately reported for agriculture, an industry dominated by a vulnerable Hispanic population and high fatal and nonfatal injury rates. Work-related illnesses can contribute to missed work, caused by a combination of personal and work factors, with costs to the individual, employer, and society. To better understand agricultural occupational illnesses, 225 Hispanic horse workers were interviewed via community-based convenience sampling. Descriptive statistics, bivariate analyses, and log binomial regression modeling were used to: (1) describe the prevalence of missed work due to work-related illnesses among Hispanic horse workers, (2) examine work-related and personal factors associated with missed work, and …

Describing Independent And Chain Pharmacies Within The Kentucky Medicaid Network, Kimber Woodrum

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

The shift in healthcare towards cost-savings mechanisms is hindering business operations of pharmacies in Kentucky, especially independent pharmacies. Independent pharmacists have reported that the operations of pharmacy benefit managers within Kentucky Medicaid networks have created financial hardships for their pharmacies and there is a threat of closure that could be associated with a potential access barrier to pharmacy services for Medicaid beneficiaries. During legislative meetings, much focus was on this issue and several bills are currently being drafted to correct this issue. It is important to define independent pharmacy and describe, geographically and in terms of utilization, chain and independent …

Retrospective Policy Analysis On The Efficacy Of The Army Hearing Program, Ahmad Brandelle Alexander

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

The present study (1) examined the Army Hearing Program (AHP) and (2) provided a retrospective policy analysis on several of the policies embedded within the AHP, more specifically the hearing readiness policy, to determine their efficacy and impact regarding noise-induced hearing loss (NIHL). The Beaufort Longest Framework was the analytic framework for this project. It was also used to structure the writing and formatting of this report. An extensive literature review of Army Medical Department (AMEDD) journals and Public Health journals were used in addition to several published Army Regulations and Pamphlets for guidance within conducting the Methods section of …

Select Antimicrobial Resistance Trends In Kentucky’S Bovine Population And Antibiogram Development, Jessica Morehouse

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Introduction: Antimicrobial resistance (AMR) is a complex problem that affects all of society and is driven by many interconnected factors. It is important to monitor AMR trends in veterinary medicine to accurately pursue appropriate antibiotic treatment of ill animals. Antibiogram development is also an important tool in guiding the veterinary practitioner in treating empirically or while a culture and susceptibility is being performed.

Methods: This study compared bacterial susceptibility in voluntary samples submitted to the University of Kentucky Veterinary Diagnostic Laboratory and the Murray State University Breathitt Veterinary Center between 2012 and 2017. Equality of proportions was used to compare …

Overdose Prevention And Naloxone Distribution In Jefferson County, Brittany Coleman

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

The United States in battling an opioid epidemic, and rates of overdose fatality have soared to record highs. Kentucky is among the states with highest rates of opioid overdose fatality, and Jefferson County is responsible for about a quarter of all cases. Overdose Prevention and Naloxone Distribution (OPND) programs have been shown to decrease fatality rates by providing a medication that literally reverses opioid overdose. The programs provide other services such as education and connection to recovery facilities.

Currently, the Kentucky Harm Reduction Coalition provides naloxone kits to the residents of Jefferson County, but they do not have a regular …

An Optimized Solid-Phase Reduction And Capture Strategy For The Study Of Reversibly-Oxidized Cysteines And Its Application To Metal Toxicity, John Andrew Hitron

Theses and Dissertations--Toxicology and Cancer Biology

The reversible oxidation of cysteine by reactive oxygen species (ROS) is both a mechanism for cellular protein signaling as well as a cause of cellular injury and death through the generation of oxidative stress. The study of cysteine oxidation is complicated by the methodology currently available to isolate and enrich oxidized-cysteine containing proteins. We sought to simplify this process by reducing the time needed to process samples and reducing sample loss and contamination risk.

We accomplished this by eliminating precipitation steps needed for the protocol by (a) introducing an in-solution NEM-quenching step prior to reduction and (b) replacing soluble dithiothreitol …

Aggressive Diuresis And Severity-Adjusted Length Of Hospital Stay In Acute Congestive Heart Failure Patients, Muhammad U. Butt

Theses and Dissertations--Clinical Research Design

To see if aggressive diuresis in first twenty four hours is associated with a comparable number of total days in the hospital as compared to non-aggressive diuresis. In this retrospective cohort study, we compared the length of hospital stay of consecutive patients admitted in one year based on their diuresis during the first twenty-four hours of hospitalization: aggressive diuresis (group 1) i.e. > 2400mL versus non-aggressive diuresis (group 2) i.e. ≤ 2400mL urine output. Patients were excluded if in cardiogenic shock, had creatinine level above 3 mg/dL on admission, or on dialysis. A total of 194 patients were enrolled (29 in …

Uterine Corpus Malignancies In Appalachia Kentucky: Incidence, Survival And Related Health Disparities, Marian Symmes Johnson

Theses and Dissertations--Clinical Research Design

Uterine cancer is the nation’s most common gynecologic malignancy but is understudied in the geographically and socioeconomically diverse state of Kentucky (KY). This study assessed the frequency, distribution, and survival of uterine corpus malignancies in KY, and specifically the differences between Appalachia (AP) and non-Appalachia (NAP).

This study utilizes SEER and Kentucky Cancer Registries to study uterine corpus malignancy between January 1, 2000 and December 31, 2014. The analysis looks at incidence between diagnoses in AP and NAP. Evaluation criteria includes: tumor histology (Type I, Type II, sarcoma, and mixed uterine malignancy), age, race, smoking status, stage at diagnosis, insurance …

Modeling Geographic Factors And Assessing Their Accuracy In Identifying Health Disparities In Fayette County, Ian Jones

Lewis Honors College Capstone Collection

The purpose of this capstone is to conduct a review of existing literature to determine the effects of a variety of geographic variables on health and wellness. The student will use their findings to create a visual aid to displaying these geographic factors and their distributions within Fayette County. Furthermore, the student will analyze the intersection of these variables to predict potential pockets of discrepancy within Fayette County. Based on this analysis, the student will propose possible interventions with a basis in current literature. This project will provide the student with the opportunity to conduct a study of existing literature, …

Health Promotion In Elementary School Students, Madelyn J. Miles

Lewis Honors College Capstone Collection

The following project was created to address the rising epidemic of childhood obesity. Childhood obesity is caused by many factors such as genetics, metabolism, community and neighborhood design, diet, exercise, and short sleep duration (Center for Disease Control: Childhood Obesity Facts). Social determinants of health, systems of oppression, and stigma can all influence the obesity epidemic. These include but are not limited to social status, location, culture, age, sexuality, ethnicity, and race. These identities can influence affordability and access to healthcare and further contribute to the obesity epidemic. It is important to understand these issues as a future provider. A …

University Of Kentucky Rural Physician Leadership Program: A Programmatic Review, Paula K. Arnett, Terry D. Stratton, Anthony D. Weaver, Carol L. Elam

Health Management and Policy Faculty Publications

This article describes the characteristics and results of the Rural Physician Leadership Program (RPLP) at the University of Kentucky College of Medicine. RPLP is a successful example of a regional medical campus designed to train physicians at a regional medical campus to serve rural areas through local partnerships.