Medicine and Health Sciences Commons^™

Thrombospondin1 Deficiency Attenuates Obesity-Associated Microvascular Complications In Apoe-/- Mice, Hasiyeti Maimaitiyiming, Kate Clemons, Qi Zhou, Heather Norman, Shuxia Wang

Pharmacology and Nutritional Sciences Faculty Publications

Obesity is associated with insulin resistance and the increased development of vascular complications. Previously, we have demonstrated that thrombospondin1 (TSP1) regulates macrophage function and contributes to obesity associated inflammation and insulin resistance. However, the role of TSP1 in the development of obesity associated vascular complications is not clear. Therefore, in the current study, we investigated whether TSP1 deficiency protects mice from obesity associated micro as well as macro-vascular complications in ApoE-/- mice. In this study, male ApoE-/- mice and ApoE-/-TSP1-/- mice were fed with a low-fat (LF) or a high-fat (HF) diet for 16 weeks. We found that body weight …

Practice-Based Research Networks For Next-Generation Public Health, Glen P. Mays

Health Management and Policy Presentations

U.S. public health agencies face an existential imperative to transform their work from a collection of discrete programs and policies into a coherent enterprise for population-wide health improvement. Practice-based research networks (PBRNs) and the advancing science of public health delivery systems can help to achieve this transformation.

Discerning Applicants' Interests In Rural Medicine: A Textual Analysis Of Admission Essays, Carol L. Elam, Anthony D. Weaver, Elmer T. Whittler, Terry D. Stratton, Linda M. Asher, Kimberly L. Scott, Emery A. Wilson

Medical Student Education Faculty Publications

BACKGROUND: Despite efforts to construct targeted medical school admission processes using applicant-level correlates of future practice location, accurately gauging applicants' interests in rural medicine remains an imperfect science. This study explores the usefulness of textual analysis to identify rural-oriented themes and values underlying applicants' open-ended responses to admission essays.

METHODS: The study population consisted of 75 applicants to the Rural Physician Leadership Program (RPLP) at the University of Kentucky College of Medicine. Using WordStat, a proprietary text analysis program, applicants' American Medical College Application Service personal statement and an admission essay written at the time of interview were searched for …

Surgical Considerations Of Lvad Implantation In Patients With Prosthetic Valves, Igor D. Gregoric

The VAD Journal

No abstract provided.

Drug Synergy Drives Conserved Pathways To Increase Fission Yeast Lifespan, Xinhe Huang, Markos Leggas, Robert C. Dickson

Pharmaceutical Sciences Faculty Publications

Aging occurs over time with gradual and progressive loss of physiological function. Strategies to reduce the rate of functional loss and mitigate the subsequent onset of deadly age-related diseases are being sought. We demonstrated previously that a combination of rapamycin and myriocin reduces age-related functional loss in the Baker's yeast Saccharomyces cerevisiae and produces a synergistic increase in lifespan. Here we show that the same drug combination also produces a synergistic increase in the lifespan of the fission yeast Schizosaccharomyces pombe and does so by controlling signal transduction pathways conserved across a wide evolutionary time span ranging from yeasts to …

The Impact Of Emotional Intelligence On Conditions Of Trust Among Leaders At The Kentucky Department For Public Health, Jennifer Redmond Knight, Heather M. Bush, William A. Mase, Martha Cornwell Riddell, Meng Liu, James W. Holsinger Jr.

Health Management and Policy Faculty Publications

There has been limited leadership research on emotional intelligence and trust in governmental public health settings. The purpose of this study was to identify and seek to understand the relationship between trust and elements of emotional intelligence, including stress management, at the Kentucky Department for Public Health (KDPH). The KDPH serves as Kentucky’s state governmental health department. KDPH is led by a Commissioner and composed of seven primary divisions and 25 branches within those divisions. The study was a non-randomized cross-sectional study utilizing electronic surveys that evaluated conditions of trust among staff members and emotional intelligence among supervisors. Pearson correlation …

Refining And Improving The Methodology For The National Health Security Preparedness Index, Glen P. Mays

Health Management and Policy Presentations

This first meeting of two newly reconstituted Working Groups for the National Health Security Preparedness Index Program examined opportunities for improving and refining the Index's measurement, scaling, weighting, and aggregation methodologies. Methodological improvements will enhance the Index's utility for education, planning, policy development, and quality improvement efforts focused on improving national preparedness and resiliency for large-scale health threats.

Collective Impact Through Public Health And Academic Partnerships: A Kentucky Public Health Accreditation Readiness Example, Angela L. Carman

Health Management and Policy Faculty Publications

In the ever-changing, resource-limited public health environment, the use of partners found in the faculty and students of Colleges of Public Health can provide training, consultation, and technical assistance needed to increase local health department (LHD) workforce capacity to meet new public health demands including national public heath accreditation. This manuscript describes the provision of the backbone support activities of facilitation, data management, and project management by University of Kentucky’s College of Public Health to Kentucky’s LHDs seeking national public health accreditation.

Cd47 Deficiency Protects Mice From Diet-Induced Obesity And Improves Whole Body Glucose Tolerance And Insulin Sensitivity, Hasiyeti Maimaitiyiming, Heather Norman, Qi Zhou, Shuxia Wang

Pharmacology and Nutritional Sciences Faculty Publications

CD47 is a transmembrane protein with several functions including self-recognition, immune cell communication, and cell signaling. Although it has been extensively studied in cancer and ischemia, CD47 function in obesity has never been explored. In this study, we utilized CD47 deficient mice in a high-fat diet induced obesity model to study for the first time whether CD47 plays a role in the development of obesity and metabolic complications. Male CD47 deficient and wild type (WT) control mice were fed with either low fat (LF) or high fat (HF) diets for 16 weeks. Interestingly, we found that CD47 deficient mice were …

Characteristics Of Clinical Shoulder Research Over The Last Decade: A Review Of Shoulder Articles In The Journal Of Bone & Joint Surgery From 2004 To 2014, Gary M. Gartsman, Brent J. Morris, R. Zackary Unger, Mitzi S. Laughlin, Hussein A. Elkousy, T. Bradley Edwards

Orthopaedic Surgery and Sports Medicine Faculty Publications

Background: The purpose of this study was to determine characteristics and trends in published shoulder research over the last decade in a leading orthopaedic journal.

Methods: We examined all clinical shoulder articles published in The Journal of Bone & Joint Surgery from 2004 to 2014. The number of citations, authorship, academic degrees of the authors, country and institution of origin, topic, level of evidence, positive or nonpositive outcome, and inclusion of validated patient-reported outcome measures were assessed for each article.

Results: Shoulder articles that included an author with an advanced research degree (MD [Doctor of Medicine] with a PhD …

The Journey Toward Voluntary Public Health Accreditation Readiness In Local Health Departments: Leadership And Followership Theories In Action, Angela L. Carman

Health Management and Policy Faculty Publications

Local health department directors’ intent on getting their organizations ready for accreditation must embrace the blurring of leader/follower lines and create an accreditation readiness team fueled not by traditional leader or follower roles but by teamship.

Unlocking The Mysteries Of Tdp-43, Keith A. Josephs, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

No abstract provided.

Metabolic Reprogramming Of Cancer-Associated Fibroblasts By Idh3Α Downregulation, Daoxiang Zhang, Yongbin Wang, Zhimin Shi, Jingyi Liu, Pan Sun, Xiaodan Hou, Jian Zhang, Shimin Zhao, Binhua P. Zhou, Jun Mi

Markey Cancer Center Faculty Publications

Cancer-associated fibroblasts (CAFs) provide critical metabolites for tumor growth and undergo metabolic reprogramming to support glycolysis. However, the molecular mechanisms responsible for this change remain unclear. Here, we report that TGF-β1- or PDGF-induced CAFs switch from oxidative phosphorylation to aerobic glycolysis. We identify downregulation of isocitrate dehydrogenase 3α (IDH3α) as a marker for this switch. Furthermore, miR-424 downregulates IDH3α during CAF formation. Downregulation of IDH3α decreases the effective level of α-ketoglutarate (α-KG) by reducing the ratio of α-KG to fumarate and succinate, resulting in PHD2 inhibition and HIF-1α protein stabilization. The accumulation of HIF-1α, in turn, promotes glycolysis by increasing …

Small Drusen And Age-Related Macular Degeneration: The Beaver Dam Eye Study, Ronald Klein, Chelsea E. Myers, Kristine E. Lee, Ronald E. Gangnon, Theru A. Sivakumaran, Sudha K Iyengar, Barbara E. K. Klein

Pathology and Laboratory Medicine Faculty Publications

We tested the hypothesis that large areas of small hard drusen (diameter <63 μm) and intermediate drusen (diameter 63-124 μm) are associated with the incidence of age-related macular degeneration (AMD). Eyes of 3344 older adults with at least 2 consecutive visits spaced 5 years apart over a 20-year period were included. A 6-level severity scale including no drusen, 4 levels of increasing area (from minimal (<2596 μm²) to large (>9086 μm²)) of only small hard drusen, and intermediate drusen was used. The 5-year incidence of AMD was 3% in eyes at the start of the interval with no, minimal, small, and moderate areas of only small drusen and 5% and 25% for eyes with large area of only small drusen and intermediate drusen, respectively. Compared to eyes with a moderate area of small drusen, the odds ratio (OR) of developing AMD in eyes with a large area of only small …

A Practical Algorithm For Managing Alzheimer's Disease: What, When, And Why?, Jeffrey L. Cummings, Richard S. Isaacson, Frederick A. Schmitt, Drew M. Velting

Sanders-Brown Center on Aging Faculty Publications

Alzheimer's disease (AD) is the most common form of dementia and its prevalence is increasing. Recent developments in AD management provide improved ways of supporting patients and their caregivers throughout the disease continuum. Managing cardiovascular risk factors, maintaining an active lifestyle (with regular physical, mental and social activity) and following a Mediterranean diet appear to reduce AD risk and may slow cognitive decline. Pharmacologic therapy for AD should be initiated upon diagnosis. All of the currently available cholinesterase inhibitors (ChEIs; donepezil, galantamine, and rivastigmine) are indicated for mild-to-moderate AD. Donepezil (10 and 23 mg/day) and rivastigmine transdermal patch (13.3 mg/24 …

Mitochondria-Associated Micrornas In Rat Hippocampus Following Traumatic Brain Injury, Wang-Xia Wang, Nishant P. Visavadiya, Jignesh D. Pandya, Peter T. Nelson, Patrick G. Sullivan, Joe E. Springer

Sanders-Brown Center on Aging Faculty Publications

Traumatic brain injury (TBI) is a major cause of death and disability. However, the molecular events contributing to the pathogenesis are not well understood. Mitochondria serve as the powerhouse of cells, respond to cellular demands and stressors, and play an essential role in cell signaling, differentiation, and survival. There is clear evidence of compromised mitochondrial function following TBI; however, the underlying mechanisms and consequences are not clear. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression post-transcriptionally, and function as important mediators of neuronal development, synaptic plasticity, and neurodegeneration. Several miRNAs show altered expression following TBI; however, the …

Brief Report: Evidence Of Ingroup Bias On The Shooter Task In A Saudi Sample, Timothy P. Schofield, Timothy Deckman, Christopher P. Garris, C. Nathan Dewall, Thomas F. Denson

Psychology Faculty Publications

When predominantly White participants in Western countries are asked to shoot individuals in a computer game who may carry weapons, they show a greater bias to shoot at outgroup members and people stereotyped as dangerous. The goal was to determine the extent to which shooter biases in the Middle East would vary as a function of target ethnicity and culturally appropriate or inappropriate headgear. Within a sample of 37 male Saudi Arabian residents, we examined shooter biases outside of Western nations for the first time. Targets in this task were either White or Middle Eastern in appearance, and wore either …

Successful Left Ventricular Assist Device Support In Patient With Bjork-Shiley Mitral Valve Replacement, Navin Rajagopalan, David C. Booth

The VAD Journal

There is limited clinical experience with left ventricular assist device therapy in patients with prosthetic mitral valves. We present a case of successful left ventricular assist device support in a patient with previous mechanical mitral valve replacement.

Regulation Of Mammalian Nucleotide Metabolism And Biosynthesis, Andrew N. Lane, Teresa W-M Fan

Toxicology and Cancer Biology Faculty Publications

Nucleotides are required for a wide variety of biological processes and are constantly synthesized de novo in all cells. When cells proliferate, increased nucleotide synthesis is necessary for DNA replication and for RNA production to support protein synthesis at different stages of the cell cycle, during which these events are regulated at multiple levels. Therefore the synthesis of the precursor nucleotides is also strongly regulated at multiple levels. Nucleotide synthesis is an energy intensive process that uses multiple metabolic pathways across different cell compartments and several sources of carbon and nitrogen. The processes are regulated at the transcription level by …

Old Dog, New Tricks - Usefulness Of The Ecg In Monitoring Acute Rejection Post Cardiac Transplantation, Paul Anaya, Samy-Claude Elayi

The VAD Journal

Electrocardiographic abnormalities have been described in the setting of acute rejection following orthotopic cardiac transplantation. The following is a brief commentary related to an interesting case report by Goldraich et al. which was recently published in the VAD Journal.

Pharmacologically Distinct Nicotinic Acetylcholine Receptors Drive Efferent-Mediated Excitation In Calyx-Bearing Vestibular Afferents, J. Chris Holt, Kevin Kewin, Paivi M. Jordan, Peter Cameron, Marcin Klapczynski, J. Michael Mcintosh, Peter A. Crooks, Linda P. Dwoskin, Anna Lysakowski

Pharmaceutical Sciences Faculty Publications

Electrical stimulation of vestibular efferent neurons rapidly excites the resting discharge of calyx/dimorphic (CD) afferents. In turtle, this excitation arises when acetylcholine (ACh), released from efferent terminals, directly depolarizes calyceal endings by activating nicotinic ACh receptors (nAChRs). Although molecular biological data from the peripheral vestibular system implicate most of the known nAChR subunits, specific information about those contributing to efferent-mediated excitation of CD afferents is lacking. We sought to identify the nAChR subunits that underlie the rapid excitation of CD afferents and whether they differ from α9α10 nAChRs on type II hair cells that drive efferent-mediated inhibition in adjacent bouton …

Inhibition Of Inos As A Novel Effective Targeted Therapy Against Triple-Negative Breast Cancer, Sergio Granados-Principal, Yi Liu, Maria L. Guevara, Elvin Blanco, Dong Soon Choi, Wei Qian, Tejal Patel, Angel A. Rodriguez, Joseph Cusimano, Heidi L. Weiss, Hong Zhao, Melissa D. Landis, Bhuvanesh Dave, Steven S. Gross, Jenny C. Chang

Markey Cancer Center Faculty Publications

INTRODUCTION: Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with no effective targeted therapy. Inducible nitric oxide synthase (iNOS) is associated with poor survival in patients with breast cancer by increasing tumor aggressiveness. This work aimed to investigate the potential of iNOS inhibitors as a targeted therapy for TNBC. We hypothesized that inhibition of endogenous iNOS would decrease TNBC aggressiveness by reducing tumor initiation and metastasis through modulation of epithelial-mesenchymal transition (EMT)-inducing factors.

METHODS: iNOS protein levels were determined in 83 human TNBC tissues and correlated with clinical outcome. Proliferation, mammosphere-forming efficiency, migration, and EMT transcription factors …

Horror Vacui: Emptiness Might Distinguish Between Major Suicide Repeaters And Nonmajor Suicide Repeaters: A Pilot Study, Hilario Blasco-Fontecilla, Enrique Baca-Garcia, Philippe Courtet, Rebeca Garcia Nieto, Jose De Leon

Psychiatry Faculty Publications

No abstract provided.

Uv-Independent Induction Of Beta Defensin 3 In Neonatal Human Skin Explants, Erin M. Wolf Horrell, John A. D'Orazio

Markey Cancer Center Faculty Publications

In order to determine the effect of UV radiation on β-defensin 3 (BD3) expression in human skin, freshly-isolated UV-naïve skin was obtained from newborn male infants undergoing planned circumcision. Skin explants sustained ex vivo dermis side down on RPMI media were exposed to 0.5 kJ/m² UVB, and biopsies were taken from the explant through 72 hours after radiation. mRNA expression was measured by qRTPCR and normalized to TATA-binding protein. BD3 expression at each time point was compared with an untreated control taken at time 0 within each skin sample. Extensive variability in both the timing and magnitude of BD3 …

Toll Like Receptor (Tlr) Stimulation For Ocular Angiogenesis And Macular Degeneration, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Patents

Provided are methods and compositions for the treatment or prevention of ocular angiogenesis and neovascularization. Administration of stimulators of the TLR3 and TLR7 receptors, Trif or of IL-10 and IL-12 inhibits ocular angiogenesis. Furthermore, all siRNAs (both targeted and non-targeted) can inhibit ocular angiogenesis.

Estimating The Costs Of Foundational Public Health Services, Glen P. Mays, Cezar B. Mamaril

UKCPHSSR Research Briefs and Reports

The Institute of Medicine’s 2012 report on public health financing called for the convening of expert panels to identify the components of a “minimum package” of public health services and cross-cutting capabilities that should be available in every U.S. community to protect and improve population health. This report also called for studies to identify the resources required to make these services universally available across the country. This research brief describes the research methodology in use to generate first-generation estimates of current resource use and estimated resource needs for implementing foundational public health services and capabilities.

Defining Comprehensive Public Health Delivery Systems, National Coordinating Center For Public Health Services And Systems Research

Health Management and Policy Reports

This brief describes the methodology for defining Comprehensive Public Health Delivery Systems using data from the National Longitudinal Survey of Public Health Systems. The systems meeting this definition have been shown to deliver a broader range of recommended public health services, using fewer resources, than the more prevalent types of U.S. public health systems that do not meet this definition. Over time, comprehensive systems are associated with larger gains in population health status than are their counterparts.

Systems-Based Analysis Of The Sarcocystis Neurona Genome Identifies Pathways That Contribute To A Heteroxenous Life Cycle, Tomasz Blazejewski, Nirvana Nursimulu, Viviana Pszenny, Sriveny Dangoudoubiyam, Sivaranjani Namasivayam, Melissa A. Chiasson, Kyle Chessman, Michelle Tonkin, Lakshmipuram S. Swapna, Stacy S. Hung, Joshua Bridgers, Stacy M. Ricklefs, Martin J. Boulanger, Jitender P. Dubey, Stephen F. Porcella, Jessica C. Kissinger, Daniel K. Howe, Michael E. Grigg, John Parkinson

Veterinary Science Faculty Publications

Sarcocystis neurona is a member of the coccidia, a clade of single-celled parasites of medical and veterinary importance including Eimeria, Sarcocystis, Neospora, and Toxoplasma. Unlike Eimeria, a single-host enteric pathogen, Sarcocystis, Neospora, and Toxoplasma are two-host parasites that infect and produce infectious tissue cysts in a wide range of intermediate hosts. As a genus, Sarcocystis is one of the most successful protozoan parasites; all vertebrates, including birds, reptiles, fish, and mammals are hosts to at least one Sarcocystis species. Here we sequenced Sarcocystis neurona, the causal agent of fatal equine protozoal myeloencephalitis. The …

Old School Still Has Merit: Ecg As A Marker Of Cardiac Recovery At Weaning From Mechanical Circulatory Support, Livia Adams Goldraich, Vivek Rao, Fillio Billia, Heather Joan Ross

The VAD Journal

In a case of acute cardiac allograft failure requiring temporary mechanical circulatory support (MCS), serial electrocardiograms (ECG) denoted the degree of myocardial inflammation and damage caused by severe rejection and subsequent recovery. This case highlights the relevance of the ECG during temporary MCS and suggests that resolution of acute electrocardiographic abnormalities might be a marker of myocardial recovery to help guide appropriate timing for weaning from MCS in the setting of acute graft failure.

Diagnosis Of Strongylus Vulgaris, Martin K. Nielsen, Ulla Anderson, Daniel K. Howe

Veterinary Science Faculty Patents

Embodiments of the presently-disclosed subject matter provide an isolated polypeptide comprising the sequence of SEQ ID NO: 1, fragments thereof, and/or epitopes thereof. Embodiments of the presently-disclosed subject matter also provide methods for diagnosing a Strongylus vulgaris infection in a subject that comprises providing a biological sample from the subject and contacting the sample with the present isolated polypeptide, fragment thereof, and/or epitope thereof. In some embodiments theStrongylus vulgaris infection can be detected during a prepatent period. In further embodiments the subject is a horse.