Medicine and Health Sciences Commons^™

Obesity Reduces Left Ventricular Strains, Torsion, And Synchrony In Mouse Models: A Cine Displacement Encoding With Stimulated Echoes (Dense) Cardiovascular Magnetic Resonance Study, Sage P. Kramer, David K. Powell, Christopher M. Haggerty, Cassi M. Binkley, Andrea C. Mattingly, Lisa A. Cassis, Frederick H. Epstein, Brandon K. Fornwalt

Pediatrics Faculty Publications

BACKGROUND: Obesity affects a third of adults in the US and results in an increased risk of cardiovascular mortality. While the mechanisms underlying this increased risk are not well understood, animal models of obesity have shown direct effects on the heart such as steatosis and fibrosis, which may affect cardiac function. However, the effect of obesity on cardiac function in animal models is not well-defined. We hypothesized that diet-induced obesity in mice reduces strain, torsion, and synchrony in the left ventricle (LV).

METHODS: Ten 12-week-old C57BL/6 J mice were randomized to a high-fat or low-fat diet. After 5 months on …

The Public Health Pbrn Program: A Summative Report, Center For Public Health Systems And Services Research

UKCPHSSR Research Briefs and Reports

This program seeks to expand the volume and quality of evidence on how best to organize, finance, and deliver public health services by: (1) helping to organize and develop practice-based research networks (PBRNs) comprised of public health agencies and skilled research institutions; (2) selecting grantees to receive funding and technical assistance for PBRN research projects; and (3) facilitating the successful development, implementation, and translation of research projects through PBRNs by providing technical assistance, fostering peer learning, and leading selected multi-network research activities.

Sphingosine-1-Phosphate-Mediated Mobilization Of Hematopoietic Stem/Progenitor Cells During Intravascular Hemolysis Requires Attenuation Of Sdf-1-Cxcr4 Retention Signaling In Bone Marrow, Kasia Mierzejewska, Yuri M. Klyachkin, Janina Ratajczak, Ahmed Abdel-Latif, Magda Kucia, Mariusz Z. Ratajczak

Saha Cardiovascular Research Center Faculty Publications

Sphingosine-1-phosphate (S1P) is a crucial chemotactic factor in peripheral blood (PB) involved in the mobilization process and egress of hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM). Since S1P is present at high levels in erythrocytes, one might assume that, by increasing the plasma S1P level, the hemolysis of red blood cells would induce mobilization of HSPCs. To test this assumption, we induced hemolysis in mice by employing phenylhydrazine (PHZ). We observed that doubling the S1P level in PB from damaged erythrocytes induced only a marginally increased level of mobilization. However, if mice were exposed to PHZ together with the …

Inflammatory Cytokine Gene Expression In Mesenteric Adipose Tissue During Acute Experimental Colitis, William Conan Mustain, Marlene E. Starr, Joseph Daniel Valentino, Donald A. Cohen, Daiki Okamura, Chi Wang, B. Mark Evers, Hiroshi Saito

Markey Cancer Center Faculty Publications

BACKGROUND: Production of inflammatory cytokines by mesenteric adipose tissue (MAT) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Animal models of colitis have demonstrated inflammatory changes within MAT, but it is unclear if these changes occur in isolation or as part of a systemic adipose tissue response. It is also unknown what cell types are responsible for cytokine production within MAT. The present study was designed to determine whether cytokine production by MAT during experimental colitis is depot-specific, and also to identify the source of cytokine production within MAT.

METHODS: Experimental colitis was induced in 6-month-old C57BL/6 …

Regulation Of Pten Inhibition By The Pleckstrin Homology Domain Of P-Rex2 During Insulin Signaling And Glucose Homeostasis, Cindy Hodakoski, Benjamin D. Hopkins, Douglas Barrows, Sarah M. Mense, Megan Keniry, Karen E. Anderson, Philip A. Kern, Phillip T. Hawkins, Len R. Stephens, Ramon Parsons

Clinical and Translational Science Faculty Publications

Insulin activation of phosphoinositide 3-kinase (PI3K) signaling regulates glucose homeostasis through the production of phosphatidylinositol 3,4,5-trisphosphate (PIP3). The dual-specificity phosphatase and tensin homolog deleted on chromosome 10 (PTEN) blocks PI3K signaling by dephosphorylating PIP3, and is inhibited through its interaction with phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 2 (P-REX2). The mechanism of inhibition and its physiological significance are not known. Here, we report that P-REX2 interacts with PTEN via two interfaces. The pleckstrin homology (PH) domain of P-REX2 inhibits PTEN by interacting with the catalytic region of PTEN, and the inositol polyphosphate 4-phosphatase domain of P-REX2 provides high-affinity binding to the postsynaptic …

Transvaginal Ultrasonography In Ovarian Cancer Screening: Current Perspectives, John R. Van Nagell Jr., John T. Hoff

Obstetrics and Gynecology Faculty Publications

Transvaginal ultrasonography (TVS) is an integral part of all major ovarian cancer screening trials. TVS is accurate in detecting abnormalities in ovarian volume and morphology, but is less reliable in differentiating benign from malignant ovarian tumors. When used as the only screening test, TVS is sensitive, but has a low positive predictive value. Therefore, serum biomarkers and tumor morphology indexing are used together with TVS to identify ovarian tumors at high risk for malignancy. This allows preoperative triage of high-risk cases to major cancer centers for therapy while decreasing unnecessary surgery for benign disease. Ovarian cancer screening has been associated …

Valproic Acid Causes Proteasomal Degradation Of Dicer And Influences Mirna Expression, Zhaiyi Zhang, Paolo Convertini, Manli Shen, Xiu Xu, Frédéric Lemoine, Pierre De La Grange, Douglas A. Andres, Stefan Stamm

Molecular and Cellular Biochemistry Faculty Publications

Valproic acid (VPA) is a commonly used drug to treat epilepsy and bipolar disorders. Known properties of VPA are inhibitions of histone deacetylases and activation of extracellular signal regulated kinases (ERK), which cannot fully explain VPA's clinical features. We found that VPA induces the proteasomal degradation of DICER, a key protein in the generation of micro RNAs. Unexpectedly, the concentration of several micro RNAs increases after VPA treatment, which is caused by the upregulation of their hosting genes prior to DICER degradation. The data suggest that a loss of DICER protein and changes in micro RNA concentration contributes to the …

Evaluating Quality Improvement To Improve Hiv Reporting, Nandi A. Marshall, William C. Livingood, Angela Peden, Gulzar H. Shah, Russ Toal, Dayna Alexander, Alesha Wright, Sandra Jump, Shelby Freeman, Kay Davis, Lynn Woodhouse, Kellie Penix

Frontiers in Public Health Services and Systems Research

The incorporation and evaluation of Quality Improvement into Georgia’s public health systems continues to be a focus of the Georgia Public Health Practice Based Research Network. This report describes the process, preliminary results and lessons learned from incorporating Quality Improvement into one of Georgia’s public health districts.

Online Social Networks To The Rescue: Fulfilling The Ten Essential Public Health Services, Melanie D. Mason, Maureen P. Bezold

Frontiers in Public Health Services and Systems Research

Budget cuts and shortages in the public health workforce have contributed to the reduction of public health services in 91% of state health departments (SHDs). To adjust for these changes, health departments must discover novel ways to deliver essential public health services to their constituents. Researchers conducted a retrospective analysis of the content published on SHDs’ Twitter pages to determine if online social networks were used to fulfill the ten essential public health services. While 42 SHDs had a Twitter page, the volume and content of tweets varied. Although tweets were posted that related to all ten of the essential …

Efficiency In Public Health Service Delivery: An Analysis Of Clinical Health Services Provided By Local Health Departments In Florida, Simone R. Singh

Frontiers in Public Health Services and Systems Research

The ability of local health departments (LHDs) to provide public health services to improve the health of their communities depends to a large extent on their financial resources. More money by itself, however, does not necessarily translate into better population health. LHDs also have to use their resources in an efficient manner to achieve the best possible outcomes. This article first describes two techniques that LHDs can use to assess their efficiency at providing public health services: process costing, a technique used by management accountants, and stochastic frontier analysis, a technique used by economists. Using data for LHDs in Florida, …

Evidence Use In New York City Public Health Policymaking, Miriam J. Laugesen, Kimberley R. Isett

Frontiers in Public Health Services and Systems Research

New York City Mayor Michael R. Bloomberg has attracted national attention for his public health policy reforms. The policy process behind the reform program has received less scrutiny, especially the use of research by policymakers. We show that the process used to develop, promote, and evaluate polices is heavily based on five types of data and research. New York Department of Health and Mental Hygiene staff conducted in-depth appraisals of existing published research, used local health surveys and private laboratory surveillance data, engaged in “shoe-leather” field research, formed research collaborations within and outside government, and disseminated research to legitimize policy …

Commentary: Moving Beyond The Numbers, Effectively Using Research To Influence Policy, F. Douglas Scutchfield, Marylou Wallace

Frontiers in Public Health Services and Systems Research

This seventh issue of Frontiers reflects the variety of PHSSR. One emerging theme, however, is the notion of public health and its role in policy and policy development. PHSSR focuses on several potential users, researchers, practitioners and policy makers. As it concerns policy makers, PHSSR delivers research that allows them to make decisions about policy change that not only influences public health status, but creates healthy conditions. In this way, PHSSR essentially influences decisions about support for public health services.

Initial Impact Of Tailored Web-Based Messages About Cigarette Smoke And Breast Cancer Risk On Boys' And Girls' Risk Perceptions And Information Seeking: Randomized Controlled Trial, Chris G. Richardson, Laura L. Struik, Kenneth C. Johnson, Pamela A. Ratner, Carolyn Gotay, Jasmina Memetovic, Chizimuzo T.C. Okoli, Joan L. Bottorff

Nursing Faculty Publications

BACKGROUND: Recent evidence indicates a causal link between both active smoking and secondhand smoke (SHS) exposure and breast cancer (BC).

OBJECTIVE: The objective of the present study was to evaluate the initial reactions of girls and boys to tailored Web-based messages that describe the relationship between SHS and BC, using a parallel, single-blinded cluster randomized controlled trial.

METHODS: This trial was nested within a cycle of an ongoing longitudinal study of 1498 students from 74 secondary schools. Self-reported assessments were used to evaluate the impact of study messages on participants' risk perception and interest in obtaining additional information after participants …

Self-Reported Juvenile Firesetting: Results From Two National Survey Datasets, Carrie Howell Bowling, Joav Merrick, Hatim A. Omar

Pediatrics Faculty Publications

The main purpose of this study was to address gaps in existing research by examining the relationship between academic performance and attention problems with juvenile firesetting. Two datasets from the Achenbach System for Empirically Based Assessment (ASEBA) were used. The Factor Analysis Dataset (N = 975) was utilized and results indicated that adolescents who report lower academic performance are more likely to set fires. Additionally, adolescents who report a poor attitude toward school are even more likely to set fires. Results also indicated that attention problems are predictive of self-reported firesetting. The National Survey Dataset (N = 1158) …

Can Experienced Observers Differentiate Between Lipoma And Well-Differentiated Liposarcoma Using Only Mri?, Patrick W. O'Donnell, Anthony M. Griffin, William C. Eward, Amir Sternheim, Lawrence M. White, Jay S. Wunder, Peter C. Ferguson

Markey Cancer Center Faculty Publications

Well-differentiated liposarcoma represents a radiographic diagnostic dilemma. To determine the accuracy, interrater reliability, and relationship of stranding, nodularity, and size in the MRI differentiation of lipoma and well-differentiated liposarcoma, MRI scans of 60 patients with large (>5 cm), deep, pathologically proven lipomas or well-differentiated liposarcomas were examined by 10 observers with subspecialty training blinded to diagnosis. Observers indicated whether the amount of stranding, nodularity, and size of each tumor suggested a benign or malignant diagnosis and rendered a diagnosis of lipoma or well-differentiated liposarcoma. The accuracy, reliability, and relationship of stranding, nodularity, and size to diagnosis were calculated for …

Examining The Claim That 80-90% Of Suicide Cases Had Depression, Said Shahtahmasebi

Pediatrics Faculty Publications

No abstract provided.

The National Longitudinal Survey Of Public Health Systems: Selected Findings And Applications, Glen P. Mays

Health Management and Policy Presentations

This presentation reviews the National Longitudinal Survey of Public Health Systems and its applicability for monitoring the effects of the Affordable Care Act on public health delivery within the U.S.

Clinically Relevant Intronic Splicing Enhancer Mutation In Myelin Proteolipid Protein Leads To Progressive Microglia And Astrocyte Activation In White And Gray Matter Regions Of The Brain, Adam D. Bachstetter, Scott J. Webster, Linda J. Van Eldik, Franca Cambi

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: Mutations in proteolipid protein (PLP), the most abundant myelin protein in the CNS, cause the X-linked dysmyelinating leukodystrophies, Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia type 2 (SPG2). Point mutations, deletion, and duplication of the PLP1 gene cause PMD/SPG2 with varying clinical presentation. Deletion of an intronic splicing enhancer (ISEdel) within intron 3 of the PLP1 gene is associated with a mild form of PMD. Clinical and preclinical studies have indicated that mutations in myelin proteins, including PLP, can induce neuroinflammation, but the temporal and spatial onset of the reactive glia response in a clinically relevant mild form of PMD …

Impact Of Noise On Molecular Network Inference, Radhakrishnan Nagarajan, Marco Scutari

Biostatistics Faculty Publications

Molecular entities work in concert as a system and mediate phenotypic outcomes and disease states. There has been recent interest in modelling the associations between molecular entities from their observed expression profiles as networks using a battery of algorithms. These networks have proven to be useful abstractions of the underlying pathways and signalling mechanisms. Noise is ubiquitous in molecular data and can have a pronounced effect on the inferred network. Noise can be an outcome of several factors including: inherent stochastic mechanisms at the molecular level, variation in the abundance of molecules, heterogeneity, sensitivity of the biological assay or measurement …

Public Health Research Implementation And Translation: Evidence From Practice-Based Research Networks, Glen P. Mays, Rachel A. Hogg, Doris M. Castellanos-Cruz, Anna G. Hoover, Lizeth C. Fowler

Health and Clinical Sciences Faculty Publications

BACKGROUND: Research on how best to deliver efficacious public health strategies in heterogeneous community and organizational contexts remains limited. Such studies require the active engagement of public health practice settings in the design, implementation, and translation of research. Practice-based research networks (PBRNs) provide mechanisms for research engagement, but until now they have not been tested in public health settings.

PURPOSE: This study uses data from participants in 14 public health PBRNs and a national comparison group of public health agencies to study processes influencing the engagement of public health settings in research implementation and translation activities.

METHODS: A cross-sectional network …

Dopaminergic Modulation Of Memory And Affective Processing In Parkinson Depression, Lee X. Blonder, John T. Slevin, Richard J. Kryscio, Catherine A. Martin, Anders H. Andersen, Charles D Smith, Frederick A. Schmitt

Magnetic Resonance Imaging and Spectroscopy Center Faculty Publications

Depression is common in Parkinson's disease and is associated with cognitive impairment. Dopaminergic medications are effective in treating the motor symptoms of Parkinson's disease; however, little is known regarding the effects of dopaminergic pharmacotherapy on cognitive function in depressed Parkinson patients. This study examines the neuropsychological effects of dopaminergic pharmacotherapy in Parkinsonian depression. We compared cognitive function in depressed and non-depressed Parkinson patients at two time-points: following overnight withdrawal and after the usual morning regimen of dopaminergic medications. A total of 28 non-demented, right-handed patients with mild to moderate idiopathic Parkinson's disease participated. Ten of these patients were depressed according …

Occupational Injuries On Thoroughbred Horse Farms: A Description Of Latino And Non-Latino Workers' Experiences, Jennifer E. Swanberg, Jessica M. Clouser, Susan C. Westneat, Mary W. Marsh, Deborah B. Reed

Health, Behavior & Society Faculty Publications

Animal production is a dangerous industry and increasingly reliant on a Latino workforce. Within animal production, little is known about the risks or the occupational hazards of working on farms involved in various aspects of thoroughbred horse breeding. Extant research suggests that horse workers are at risk of musculoskeletal and respiratory symptoms, kicks, and other injuries. However, limited known research has examined the experiences of the industry's workers, including immigrant workers, despite their prominence and increased vulnerability. Using data collected from thoroughbred farm representatives via a phone-administered survey, a 2-hour face-to-face semi-structured interview, and farm injury logs, this article identifies …

Ccr3 Inhibition 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 inhibitors of the CCR3 receptor or its ligands eotaxin (CCL11), eotaxin-2 (CCL24) or eotaxin-3 (CCL26) inhibits ocular angiogenesis.

High Activity Mutants Of Butyrylcholinesterase For Cocaine Hydrolysis, Chang-Guo Zhan, Fang Zheng, Wenchao Yang, Lin Xue, Shurong Hou

Pharmaceutical Sciences Faculty Patents

Butyrylcholinesterase (BChE) polypeptide variants of the presently-disclosed subject matter have enhanced catalytic efficiency for (−)-cocaine, as compared to wild-type BChE. Pharmaceutical compositions of the presently-disclosed subject matter include a BChE polypeptide variant having an enhanced catalytic efficiency for (−)-cocaine. A method of the presently-disclosed subject matter for treating a cocaine-induced condition includes administering to an individual an effective amount of a BChE polypeptide variant, as disclosed herein, to lower blood cocaine concentration.

Estimating The Costs Of Public Health Services, Glen P. Mays

Health Management and Policy Presentations

The National Academy of Sciences Institute of Medicine recommended in 2012 that the federal government undertake work to identify the components and costs of a "minimum package" of public health programs, services, and capabilities that should be available in every American community. This presentation summarizes work that is currently underway through the Robert Wood Johnson Foundation-supported Public Health Practice-Based Research Networks (PBRN) Program to estimate the costs of public health delivery.

A Process Similar To Autophagy Is Associated With Cytocidal Chloroquine Resistance In Plasmodium Falciparum, David Gaviria, Michelle F. Paguio, Lindsey B. Turnbull, Asako Tan, Amila Siriwardana, Debasish Ghosh, Michael T. Ferdig, Anthony P. Sinai, Paul D. Roepe

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Resistance to the cytostatic activity of the antimalarial drug chloroquine (CQ) is becoming well understood, however, resistance to cytocidal effects of CQ is largely unexplored. We find that PfCRT mutations that almost fully recapitulate P. falciparum cytostatic CQ resistance (CQR(CS)) as quantified by CQ IC50 shift, account for only 10-20% of cytocidal CQR (CQR(CC)) as quantified by CQ LD50 shift. Quantitative trait loci (QTL) analysis of the progeny of a chloroquine sensitive (CQS; strain HB3)×chloroquine resistant (CQR; strain Dd2) genetic cross identifies distinct genetic architectures for CQR(CS) vs CQR(CC) phenotypes, including identification of novel interacting chromosomal loci that influence CQ …

Truck Driver Dies When Tractor-Trailer Leaves The Road And Plunges Into A Creek-Bed, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Motor Vehicle

In the early morning hours of a fall day, exact time unknown and the length of time driving unknown, a 28-year-old male truck driver was driving north on an interstate transporting 30,000 lbs. of blue plastic injection molding pellets. The truck driver exited the highway behind a guardrail and traveled 1,320 feet, striking a wire fence and several trees before plummeting into a creek bed, shearing the cab open. At 10:27 a.m., a citizen called in to the fire department to report a mysterious blue substance observed in the creek a couple of miles down from the accident. The fire …

Binding, Transcytosis And Biodistribution Of Anti-Pecam-1 Iron Oxide Nanoparticles For Brain-Targeted Delivery, Mo Dan, David B. Cochran, Robert A. Yokel, Thomas D. Dziubla

Pharmaceutical Sciences Faculty Publications

OBJECTIVE: Characterize the flux of platelet-endothelial cell adhesion molecule (PECAM-1) antibody-coated superparamagnetic iron oxide nanoparticles (IONPs) across the blood-brain barrier (BBB) and its biodistribution in vitro and in vivo.

METHODS: Anti-PECAM-1 IONPs and IgG IONPs were prepared and characterized in house. The binding affinity of these nanoparticles was investigated using human cortical microvascular endothelial cells (hCMEC/D3). Flux assays were performed using a hCMEC/D3 BBB model. To test their immunospecificity index and biodistribution, nanoparticles were given to Sprague Dawley rats by intra-carotid infusion. The capillary depletion method was used to elucidate their distribution between the BBB and brain parenchyma.

RESULTS: Anti-PECAM-1 …

Evidence For Finely-Regulated Asynchronous Growth Of Toxoplasma Gondii Cysts Based On Data-Driven Model Selection, Adam M. Sullivan, Xiaopeng Zhao, Yasuhiro Suzuki, Eri Ochiai, Stephen Crutcher, Michael A. Gilchrist

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Toxoplasma gondii establishes a chronic infection by forming cysts preferentially in the brain. This chronic infection is one of the most common parasitic infections in humans and can be reactivated to develop life-threatening toxoplasmic encephalitis in immunocompromised patients. Host-pathogen interactions during the chronic infection include growth of the cysts and their removal by both natural rupture and elimination by the immune system. Analyzing these interactions is important for understanding the pathogenesis of this common infection. We developed a differential equation framework of cyst growth and employed Akaike Information Criteria (AIC) to determine the growth and removal functions that best describe …

Amlodipine Reduces Angii-Induced Aortic Aneurysms And Atherosclerosis In Hypercholesterolemic Mice, Xiaofeng Chen, Debra L. Rateri, Deborah A. Howatt, Anju Balakrishnan, Jessica J. Moorleghen, Andrew J. Morris, Richard Charnigo, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: The purpose of this study was to determine effects of amlodipine, a dihydropyridine calcium channel blocker, on development of angiotensin II (AngII)-induced vascular pathologies.

METHODS AND RESULTS: Male LDL receptor -/- mice were infused with vehicle, amlodipine (5 mg/kg/d), AngII (1,000 ng/kg/min), or AngII + amlodipine for 4 weeks through osmotic pumps (n=10/group). Mice were fed a saturated fat-enriched diet for 1 week prior to pump implantation and during 4 weeks of infusion. Infusion of amlodipine resulted in plasma concentrations of 32 ± 2 ng/ml and 27 ± 2 ng/ml for mice in saline + amlodipine and AngII + …