Digital Commons Network^™

Anesthetic Implications Of Robotic Gynecologic Surgery, J. Thomas Mclarney, Gregory L. Rose

Anesthesiology Faculty Publications

Surgery using robotic techniques is becoming more and more common. One of the specialties at the fore-front of robotic surgery has been gynecology, much like it was at the fore-front a generation ago in bringing laparoscopy into the operating room. New considerations have been noted and new techniques have been learned on both sides of the drape in order to ensure a successful outcome for the patient undergoing robotic gynecologic surgery. The purpose of this article is to bring, to light the concerns facing the anesthesiologist in regards to robotic procedures. We discuss the problems facing anesthesiologists, when a patient …

Societal Expectations And The Profession's Responsibility To Reform The Dental Workforce To Ensure Access To Care For Children, David A. Nash

Oral Health Science Faculty Publications

Societal expectations raise the issue of the nature of a profession and a profession's relationship with society. Influential policy leaders want reform of the oral health workforce and delivery system in such a manner as to ensure that improvements are made for accessing care, particularly for vulnerable and disadvantaged populations, especially children. This essay is based on a presentation to the House of Delegates of the California Dental Association on Nov.13, 2009.

Risky Business: Liability Of Product Sellers Who Offer Safety Devices As Optional Equipment, Richard C. Ausness

Law Faculty Scholarly Articles

This Article examines the question of whether (or when) product sellers should be allowed to offer optional safety equipment without fear of being held strictly liable for selling a defectively designed product. Part II of this Article examines several approaches to risk-bearing. At one end of the spectrum, the principle of personal autonomy dictates that consumers should decide how much risk they wish to accept. On the other hand, products liability law assumes that if consumers are allowed to subject themselves to greater risk, producers will be quick to take advantage of their inability to make rational decisions about what …

Osler Came To Boston, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

No abstract provided.

Transylvania Medical Alumni Who Served In The Union And Confederate Armies, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

No abstract provided.

Farmwork-Related Injury Among Farmers 50 Years Of Age And Older In Kentucky And South Carolina: A Cohort Study, 2002-2005, Jennifer L. Marcum, Steven R. Browning, Deborah B. Reed, Richard Charnigo

Epidemiology and Environmental Health Faculty Publications

Farmers in the U.S. are becoming more diverse; the average age of the farmer is increasing, as is the number of women and minority farm operators. There is limited research on injury risk factors in these special populations of farmers. It is especially important to study the risk factors for injury in these growing and at-risk groups. A longitudinal survey was conducted of farmers (n = 1,394) age 50 and older who resided in Kentucky and South Carolina. The questionnaire was administered by telephone and mail surveys four times between 2002 and 2005 to the fixed cohort of farmers, obtained …

Identification Of The Allosteric Regulatory Site Of Insulysin, Nicholas Noinaj, Sonia K. Bhasin, Eun Suk Song, Kirsten E. Scoggin, Maria A. Juliano, Luiz Juliano, Louis B. Hersh, David W. Rodgers

Molecular and Cellular Biochemistry Faculty Publications

BACKGROUND: Insulin degrading enzyme (IDE) is responsible for the metabolism of insulin and plays a role in clearance of the Aβ peptide associated with Alzheimer's disease. Unlike most proteolytic enzymes, IDE, which consists of four structurally related domains and exists primarily as a dimer, exhibits allosteric kinetics, being activated by both small substrate peptides and polyphosphates such as ATP.

PRINCIPAL FINDINGS: The crystal structure of a catalytically compromised mutant of IDE has electron density for peptide ligands bound at the active site in domain 1 and a distal site in domain 2. Mutating residues in the distal site eliminates allosteric …

Berry Preparations And Extracts, Russell J. Mumper, Jin Dai, Vincent S. Gallicchio

Pharmaceutical Sciences Faculty Patents

A method for deriving compositions having antioxidant and anti-inflammatory activity from berries is provided. The method results in a berry extract compositions having stable anthocyanin content. In one aspect, the method comprises exposing a berry to a solvent composition having a pH of from about 1 to about 4.5, and recovering a berry extract having a stabilized anthocyanin content. The berry may be a blackberry. A cryoprotectant may be added, to further stabilize the anthocyanin content. Compositions comprising the berry extract of the present invention, formulated for oral and/or topical administration, are provided also, including nutritional supplements, capsules, enteric-coated capsules, …

Analyzing The Impact Of 23 Mg/Day Donepezil On Language Dysfunction In Moderate To Severe Alzheimer's Disease, Steven H. Ferris, Frederick A. Schmitt, Judith Saxton, Sharon Richardson, Joan Mackell, Yijun Sun, Yikang Xu

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: Progressive language impairment is among the primary components of cognitive decline in Alzheimer's disease (AD). Because expressive and receptive language help to maintain emotional connections to caregivers and support the management of AD patients' functional needs, language plays a critical role in patients' emotional and physical health. Using data from a large prospective clinical trial comparing two doses of donepezil in patients with moderate to severe AD, we performed a post hoc analysis to determine whether a higher dose of donepezil was associated with greater benefits in language function.

METHODS: In the original randomized, double-blind clinical trial, 1,467 patients …

Phssr Research Agenda, F. Douglas Scutchfield Md

Preventive Medicine and Environmental Health Presentations

No abstract provided.

Sonic Hedgehog Dependent Phosphorylation By Ck1Α And Grk2 Is Required For Ciliary Accumulation And Activation Of Smoothened, Yongbin Chen, Noriaki Sasai, Guoqiang Ma, Tao Yue, Jianhang Jia, James Briscoe, Jin Jiang

Markey Cancer Center Faculty Publications

Hedgehog (Hh) signaling regulates embryonic development and adult tissue homeostasis through the GPCR-like protein Smoothened (Smo), but how vertebrate Smo is activated remains poorly understood. In Drosophila, Hh dependent phosphorylation activates Smo. Whether this is also the case in vertebrates is unclear, owing to the marked sequence divergence between vertebrate and Drosophila Smo (dSmo) and the involvement of primary cilia in vertebrate Hh signaling. Here we demonstrate that mammalian Smo (mSmo) is activated through multi-site phosphorylation of its carboxyl-terminal tail by CK1α and GRK2. Phosphorylation of mSmo induces its active conformation and simultaneously promotes its ciliary accumulation. We demonstrate that …

Store-Operated Ca(2+) Entry (Soce) Contributes To Normal Skeletal Muscle Contractility In Young But Not In Aged Skeletal Muscle, Angela M. Thornton, Xiaoli Zhao, Noah Weisleder, Leticia S. Brotto, Sylvain Bougoin, Thomas M. Nosek, Michael B. Reid, Brian Hardin, Zui Pan, Jianjie Ma, Jerome Parness, Marco Brotto

Physiology Faculty Publications

Muscle atrophy alone is insufficient to explain the significant decline in contractile force of skeletal muscle during normal aging. One contributing factor to decreased contractile force in aging skeletal muscle could be compromised excitation-contraction (E-C) coupling, without sufficient available Ca(2+) to allow for repetitive muscle contractility, skeletal muscles naturally become weaker. Using biophysical approaches, we previously showed that store-operated Ca(2+) entry (SOCE) is compromised in aged skeletal muscle but not in young ones. While important, a missing component from previous studies is whether or not SOCE function correlates with contractile function during aging. Here we test the contribution of extracellular …

A Tale Of Two Cities? The Heterogeneous Impact Of Medicaid Managed Care In Kentucky, James Marton, Aaron Yelowitz, Jeffery C. Talbert

University of Kentucky Center for Poverty Research Discussion Paper Series

Does managed care produce lower health care utilization and costs through better aligned financial incentives and alternative delivery methods (the “pure” HMO effect) or by attracting more healthy enrollees (enrollee selection)? The purpose of this paper is to shed new light on this fundamental question using a quasi-experimental approach that exploits the timing and county specific implementation of Medicaid managed care plans in two distinct sub-sets of Kentucky counties in the late 1990s. We find large differences in the relative success of each region in reducing utilization that are likely driven by important differences in plan design. Asthmatic children enrolled …

Role Of Phosphoinositide 3-Kinase – Akt Signaling Pathway In The Age-Related Cytokine Dysregulation In Splenic Macrophages Stimulated Via Tlr-2 Or Tlr-4 Receptors, Mosoka Papa Fallah, R. Lakshman Chelvarajan, Beth A. Garvy, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Age-associated defects in both B-lymphocytes and macrophages in elderly result in a reduction in the efficacy of vaccines to many Gram positive bacteria like Streptococcus pneumoniae. Splenic macrophages from aged mice have been shown to have a defect in production of pro-inflammatory cytokines (IL-6, IL-12, IL-1β, TNF-α) but exhibit increased production of IL-10 upon TLR4 ligation. Here we showed that aged macrophages demonstrate similar cytokine dysregulation phenotype upon stimulation with TLR2 ligands, or killed S. pneumoniae. We hypothesized that an age-associated increase in activity of phosphatidyl inositol 3-kinase (PI3K)-Akt signaling pathway may be playing a causal role in …

Patient Discomfort Associated With The Use Of Intra-Arterial Iodinated Contrast Media: A Meta-Analysis Of Comparative Randomized Controlled Trials, Peter A. Mccullough, Patrizio Capasso

Radiology Faculty Publications

BACKGROUND: Discomfort characterized by pain and warmth are common adverse effects associated with the use of intra-arterial iodinated contrast media (CM). The objective of this review was to pool patient-reported outcomes available from head-to-head randomized controlled trials (RCTs) and to compare the discomfort rates associated with iso-osmolar contrast media (IOCM; i.e., iodixanol) to those reported with various low-osmolar contrast media (LOCM).

METHODS: A review of the literature published between 1990 and 2009 available through Medline, Medline Preprints, Embase, Biological Abstracts, BioBase, Cab Abstracts, International Pharmaceutical Abstracts, Life Sciences Collection, Inside Conferences, Energy Database, Engineering Index and Technology Collection was performed …

Academic Detailing To Increase Colorectal Cancer Screening By Primary Care Practices In Appalachian Pennsylvania, William J. Curry, Eugene J. Lengerich, Brenda C. Kluhsman, Marie A. Graybill, Jason Z. Liao, Eric W. Schaefer, Angela M. Spleen, Mark B. Dignan

Internal Medicine Faculty Publications

BACKGROUND: In the United States, colorectal cancer (CRC) is the third most frequently diagnosed cancer and second leading cause of cancer death. Screening is a primary method to prevent CRC, yet screening remains low in the U.S. and particularly in Appalachian Pennsylvania, a largely rural area with high rates of poverty, limited health care access, and increased CRC incidence and mortality rates. Receiving a physician recommendation for CRC screening is a primary predictor for patient adherence with screening guidelines. One strategy to disseminate practice-oriented interventions is academic detailing (AD), a method that transfers knowledge or methods to physicians, nurses or …

Rheumatoid Arthritis-Associated Polymorphisms Are Not Protective Against Alzheimer's Disease, Christopher R. Simmons, Fanggeng Zou, Steven G Younkin, Steven Estus

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Rheumatoid arthritis (RA) and Alzheimer's disease (AD) are inversely associated. To test the hypothesis that genetic elements associated with increased RA risk are associated with decreased AD risk, we evaluated RA genetic risk factors recently identified in genome-wide association studies (GWAS) for their association with AD in a two-stage, case-control analysis.

RESULTS: In our Stage 1 analysis of ~800 AD and ~1,200 non-AD individuals, three of seventeen RA-associated SNPs were nominally associated with AD (p < 0.05) with one SNP, rs2837960, retaining significance after correction for multiple testing (p = 0.03). The rs2837960_G (minor) allele, which is associated with increased RA risk, was associated with increased AD risk. Analysis of these three SNPs in a Stage 2 population, consisting of ~1,100 AD and ~2,600 non-AD individuals, did not confirm their association with AD. Analysis of Stage 1 and 2 combined suggested that rs2837960 shows a trend for association with AD. When the Stage 2 population was age-matched for the Stage 1 population, rs2837960 exhibited a non-significant trend with AD. Combined analysis of Stage 1 and the age-matched Stage 2 subset showed a significant association of rs2837960 with AD (p = 0.002, OR 1.24) that retained significance following correction for age, sex and APOE (p = 0.02, OR = 1.20). Rs2837960 is near BACE2, which encodes an aspartic protease capable of processing the AD-associated amyloid precursor protein. Testing for an association between rs2837960 and the expression of BACE2 isoforms in human brain, we observed a trend between rs2837960 and the total expression of BACE2 and the expression of a BACE2 transcript lacking exon 7 (p = 0.07 and 0.10, respectively).

CONCLUSIONS: RA-associated SNPs are generally not associated with AD. Moreover, rs2837960_G is associated with increased risk of both RA and, in individuals less than …

Recombination Phenotypes Of The Nci-60 Collection Of Human Cancer Cells, Dawn M. Stults, Michael W. Killen, Brent J. Shelton, Andrew J. Pierce

Microbiology, Immunology, and Molecular Genetics Faculty Publications

BACKGROUND: The NCI-60 is a collection of tumor cell lines derived from a variety of human adult cancer tissue types and is commonly used for genetic analysis and screening of potential chemotherapeutic agents. We wanted to understand the contributions of specific mechanisms of genomic instability to the etiology of cancers represented by the NCI-60.

RESULTS: We screened the NCI-60 for dysregulated homologous recombination by using the gene cluster instability (GCI) assay we pioneered, and for defects in base excision repair by sensitivity to 5-hydroxymethyl-2'-deoxyuridine (hmdUrd). We identified subsets of the NCI-60 lines that either displayed the characteristic molecular signature of …

Possible Role Of Death Receptor-Mediated Apoptosis By The E3 Ubiquitin Ligases Siah2 And Posh, Perry A. Christian, Michael V. Fiandalo, Steven R. Schwarze

Markey Cancer Center Faculty Publications

BACKGROUND: A functioning ubiquitin proteasome system (UPS) is essential for a number of diverse cellular processes and maintenance of overall cellular homeostasis. The ability of proteasome inhibitors, such as Velcade, to promote extrinsic apoptotic effects illustrates the importance of the ubiquitin proteasome system in the regulation of death receptor signaling. Here, we set out to define the UPS machinery, particularly the E3 ubiquitin ligases, that repress apoptosis through the extrinsic pathway. A cell-based genome-wide E3 ligase siRNA screen was established to monitor caspase-8 activity following the addition of TRAIL.

RESULTS: Data from the high-throughput screen revealed that targeting the RING-finger …

Lipid Phosphate Phosphatase 3 Enables Efficient Thymic Egress, Béatrice Bréart, Willy D. Ramos-Perez, Alejandra Mendoza, Abdelghaffar K. Salous, Michael Gobert, Yong Huang, Ralf H. Adams, Juan J. Lafaille, Diana Escalante-Alcalde, Andrew J. Morris, Susan R. Schwab

Gill Heart & Vascular Institute Faculty Publications

The signaling lipid sphingosine-1-phosphate (S1P) stabilizes the vasculature, directs lymphocyte egress from lymphoid organs, and shapes inflammatory responses. However, little is known about how S1P distribution is controlled in vivo, and it is not clear how a ubiquitously made lipid functions as a signal that requires precise spatial and temporal control. We have found that lipid phosphate phosphatase 3 (LPP3) enables efficient export of mature T cells from the thymus into circulation, and several lines of evidence suggest that LPP3 promotes exit by destroying thymic S1P. Although five additional S1P-degrading enzymes are expressed in the thymus, they cannot compensate for …

Nfatc1 Regulation Of Trail Expression In Human Intestinal Cells, Qingding Wang, Yuning Zhou, Heidi L. Weiss, Chi-Wing Chow, B. Mark Evers

Surgery Faculty Publications

TNF-related apoptosis-inducing ligand (TRAIL; Apo2) has been shown to promote intestinal cell differentiation. Nuclear factor of activated T cells (NFAT) participates in the regulation of a variety of cellular processes, including differentiation. Here, we examined the role of NFAT in the regulation of TRAIL in human intestinal cells. Treatment with a combination of phorbol 12-myristate 13-acetate (PMA) plus the calcium ionophore A23187 (Io) increased NFAT activation and TRAIL expression; pretreatment with the calcineurin inhibitor cyclosporine A (CsA), an antagonist of NFAT signaling, diminished NFAT activation and TRAIL induction. In addition, knockdown of NFATc1, NFATc2, NFATc3, and NFATc4 blocked PMA/Io increased …

Nogo-B Receptor Is Necessary For Cellular Dolichol Biosynthesis And Protein N-Glycosylation., Kenneth D Harrison, Eon Joo Park, Ningguo Gao, Andrew Kuo, Jeffrey S. Rush, Charles J Waechter, Mark A Lehrman, William C Sessa

Molecular and Cellular Biochemistry Faculty Publications

Dolichol monophosphate (Dol-P) functions as an obligate glycosyl carrier lipid in protein glycosylation reactions. Dol-P is synthesized by the successive condensation of isopentenyl diphosphate (IPP), with farnesyl diphosphate catalysed by a cis-isoprenyltransferase (cis-IPTase) activity. Despite the recognition of cis-IPTase activity 40 years ago and the molecular cloning of the human cDNA encoding the mammalian enzyme, the molecular machinery responsible for regulating this activity remains incompletely understood. Here, we identify Nogo-B receptor (NgBR) as an essential component of the Dol-P biosynthetic machinery. Loss of NgBR results in a robust deficit in cis-IPTase activity and Dol-P production, leading to diminished levels of …

Evaluation Of Human Health Risk From Potential Exposures To Fly Ash At The Tva Kingston Fly Ash Recovery Project, Mark Stack, Suzy Young, Dan Jones, Neil Carriker

World of Coal Ash Proceedings

No abstract provided.

Commercial Update On Beneficiation Process Staged Turbulent Air Reactor (Star), Jimmy Knowles, Bill Fedorka, Robbie Hendrix, John Castleman

World of Coal Ash Proceedings

No abstract provided.

Environmental And Health Aspects Of Coal And Biomass Co-Combustion Ashes, Ronald J. Van Eijk, B. Henk Te Winkel, Arthur F. Stam

World of Coal Ash Proceedings

No abstract provided.

Future Role Of Community Health Workers For Reducing Health Disparities, Frances J. Feltner, Emery Wilson, Elmer T. Whitler, Linda Asher

Center of Excellence in Rural Health Presentations

Against the backdrop of national health care reform and Kentucky’s physician shortage, this study examined the impact of community health workers (specifically, Kentucky Homeplace) on health disparities in rural, medically underserved areas. Among the conclusions are that community health workers can increase the ability of indigent residents to access health care services and their compliance with physicians’ orders.

Public Health Finance Management Needs And How Public Health Agencies Are Funded., F. Douglas Scutchfield Md

Preventive Medicine and Environmental Health Presentations

No abstract provided.

Synaptic Reorganization Of Inhibitory Hilar Interneuron Circuitry After Traumatic Brain Injury In Mice, Robert F. Hunt, Stephen W. Scheff, Bret N. Smith

Physiology Faculty Publications

Functional plasticity of synaptic networks in the dentate gyrus has been implicated in the development of posttraumatic epilepsy and in cognitive dysfunction after traumatic brain injury, but little is known about potentially pathogenic changes in inhibitory circuits. We examined synaptic inhibition of dentate granule cells and excitability of surviving GABAergic hilar interneurons 8–13 weeks after cortical contusion brain injury in transgenic mice that express enhanced green fluorescent protein in a subpopulation of inhibitory neurons. Whole-cell voltage-clamp recordings in granule cells revealed a reduction in spontaneous and miniature IPSC frequency after head injury; no concurrent change in paired-pulse ratio was found …

Novel Model For Multispecies Biofilms That Uses Rigid Gas-Permeable Lenses, Rebecca Peyyala, Sreenatha S. Kirakodu, Jeffrey L. Ebersole, Karen F. Novak

Center for Oral Health Research Faculty Publications

Oral biofilms comprise complex multispecies consortia aided by specific inter- and intraspecies interactions occurring among commensals and pathogenic bacterial species. Oral biofilms are primary initiating factors of periodontal disease, although complex multifactorial biological influences, including host cell responses, contribute to the individual outcome of the disease. To provide a system to study initial stages of interaction between oral biofilms and the host cells that contribute to the disease process, we developed a novel in vitro model system to grow biofilms on rigid gas-permeable contact lenses (RGPLs), which enable oxygen to permeate through the lens material. Bacterial species belonging to early- …

If You Don’T Build It... Mexican Mobility Following The U.S. Housing Bust, Brian C. Cadena, Brian K. Kovak

University of Kentucky Center for Poverty Research Discussion Paper Series

This paper demonstrates the importance of earnings-sensitive migration in response to local variation in labor demand. We use geographic variation in the depth of the housing bust to examine its effects on the migration of natives and Mexican-born individuals in the U.S. We find a strong effect of the housing bust on the location choices of Mexicans, with movement of Mexican population away from U.S. states facing the largest declines in construction and movement toward U.S. states facing smaller declines. This effect operated primarily through interstate migration of Mexicans previously residing in the U.S. and, to a lesser extent, through …