Medicine and Health Sciences Commons^™

Estimating Medical Cost Offsets Attributable To Public Health Spending, Glen P. Mays

Health Management and Policy Presentations

Uncertainty about the magnitude and timing of economic returns associated with spending on public health services has contributed to policy debates about the optimal role of the federal government in financing these services.

Use Of Parthenolide Derivatives As Antileukemic And Cytotoxic Agents, Peter A. Crooks, Craig T. Jordan, Xiaochen Wei

Pharmaceutical Sciences Faculty Patents

To view this abstract, please download this patent.

A Special Issue On Dna Damage Response And Genome Stability, Guo-Min Li

Markey Cancer Center Faculty Publications

No abstract provided.

Krüppel-Like Factor 4 Regulates Intestinal Epithelial Cell Morphology And Polarity, Tianxin Yu, Xi Chen, Wen Zhang, Juan Li, Ren Xu, Timothy C Wang, Walden Ai, Chunming Liu

Markey Cancer Center Faculty Publications

Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor that plays a vital role in regulating cell lineage differentiation during development and maintaining epithelial homeostasis in the intestine. In normal intestine, KLF4 is predominantly expressed in the differentiated epithelial cells. It has been identified as a tumor suppressor in colorectal cancer. KLF4 knockout mice demonstrated a decrease in number of goblet cells in the colon, and conditional ablation of KLF4 from the intestinal epithelium led to altered epithelial homeostasis. However, the role of KLF4 in differentiated intestinal cells and colon cancer cells, as well as the mechanism by which …

Active Site Mutations Change The Cleavage Specificity Of Neprilysin., Travis Sexton, Lisa J. Hitchcook, David W. Rodgers, Luke H. Bradley, Louis B. Hersh

Molecular and Cellular Biochemistry Faculty Publications

Neprilysin (NEP), a member of the M13 subgroup of the zinc-dependent endopeptidase family is a membrane bound peptidase capable of cleaving a variety of physiological peptides. We have generated a series of neprilysin variants containing mutations at either one of two active site residues, Phe⁵⁶³ and Ser⁵⁴⁶. Among the mutants studied in detail we observed changes in their activity towards leucine⁵-enkephalin, insulin B chain, and amyloid β_1-40. For example, NEP^F563I displayed an increase in preference towards cleaving leucine⁵-enkephalin relative to insulin B chain, while mutant NEP^S546E was less discriminating …

Aluminum In Food – The Nature And Contribution Of Food Additives, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

No abstract provided.

Bmi-1 Absence Causes Premature Brain Degeneration, Guangliang Cao, Minxia Gu, Min Zhu, Junying Gao, Ying Yin, Charles Marshall, Ming Xiao, Jiong Ding, Dengshun Miao

Physical Therapy Faculty Publications

Bmi-1, a polycomb transcriptional repressor, is implicated in cell cycle regulation and cell senescence. Its absence results in generalized astrogliosis and epilepsy during the postnatal development, but the underlying mechanisms are poorly understood. Here, we demonstrate the occurrence of oxidative stress in the brain of four-week-old Bmi-1 null mice. The mice showed various hallmarks of neurodegeneration including synaptic loss, axonal demyelination, reactive gliosis and brain mitochondrial damage. Moreover, astroglial glutamate transporters and glutamine synthetase decreased in the Bmi-1 null hippocampus, which might contribute to the sporadic epileptic-like seizures in these mice. These results indicate that Bmi-1 is required for maintaining …

A Placebo-Controlled, Double-Blind, Dose-Escalation Study To Assess The Safety, Tolerability And Pharmacokinetics/Pharmacodynamics Of Single And Multiple Intravenous Infusions Of Azd9773 In Patients With Severe Sepsis And Septic Shock, Peter E. Morris, Brian Zeno, Andrew C. Bernard, Xiangning Huang, Shampa Das, Timi Edeki, Steven G. Simonson, Gordon R. Bernard

Surgery Faculty Publications

INTRODUCTION: Tumor necrosis factor-alpha (TNF-α), an early mediator in the systemic inflammatory response to infection, is a potential therapeutic target in sepsis. The primary objective of this study was to determine the safety and tolerability of AZD9773, an ovine, polyclonal, anti-human TNF-α Fab preparation, in patients with severe sepsis. Secondary outcomes related to pharmacokinetic (PK) and pharmacodynamic (PD) parameters.

METHODS: In this double-blind, placebo-controlled, multicenter Phase IIa study, patients were sequentially enrolled into five escalating-dose cohorts (single doses of 50 or 250 units/kg; multiple doses of 250 units/kg loading and 50 units/kg maintenance, 500 units/kg loading and 100 units/kg maintenance, …

Method For Treating Hair Growth Disorders, Such As Female Pattern Alopecia, And Compositions Useful Therefore, Elaine L. Jacobson, Myron K. Jacobson, Hyuntae Kim, Donna L. Coyle, William R. Coyle

Graduate Center for Nutritional Sciences Faculty Patents

The invention relates to formulations useful in treating hair disorders, improving the health of hair, increasing hair growth, and in increasing the niacin content of hair follicles. Nicotinic acid alkyl esters having a straight chain alkyl group of from 1 to 22 methylene units, preferably from 6 to 16 methylene units, and most preferably from 8 to 14 methyl units, may be used, alone or in combinations for treating these conditions.

Public Health Spending, Preventable Outcomes, And Medical Cost Offsets: Questions For Health Reform, Glen P. Mays

Health Management and Policy Presentations

Uncertainty continues to surround the health and economic effects that can be expected from increased federal spending on public health and prevention strategies. Recent research provides some insight into the question of whether spending on public health strategies can offset the need for future spending on medical care.

Lithium Treatment Of Appswdi/Nos2−/− Mice Leads To Reduced Hyperphosphorylated Tau, Increased Amyloid Deposition And Altered Inflammatory Phenotype, Tiffany L. Sudduth, Joan G. Wilson, Angela Everhart, Carol A. Colton, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

Lithium is an anti-psychotic that has been shown to prevent the hyperphosphorylation of tau protein through the inhibition of glycogen-synthase kinase 3-beta (GSK3β). We recently developed a mouse model that progresses from amyloid pathology to tau pathology and neurodegeneration due to the genetic deletion of NOS2 in an APP transgenic mouse; the APPSwDI/NOS2-/- mouse. Because this mouse develops tau pathology, amyloid pathology and neuronal loss we were interested in the effect anti-tau therapy would have on amyloid pathology, learning and memory. We administered lithium in the diets of APPSwDI/NOS2-/- mice for a period of eight months, followed by water maze …

Does Place Of Residence Affect Risk Of Suicide? A Spatial Epidemiologic Investigation In Kentucky From 1999 To 2008, Daniel M. Saman, Sabrina Walsh, Anna Borówko, Agricola Odoi

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: Approximately 32,000 people take their own lives every year in the United States. In Kentucky, suicide mortality rates have been steadily increasing since 1999. Few studies in the United States have assessed spatial clustering of suicides. The purpose of this study was to identify high-risk clusters of suicide at the county level in Kentucky and assess the characteristics of those suicide cases within the clusters.

METHODS: A spatial epidemiological study was undertaken using suicide data for the period January 1, 1999 to December 31, 2008, obtained from the Kentucky Office of Vital Statistics. Descriptive analyses using Pearson's chi-square test …

Ex Vivo And In Vivo Methods And Related Compositions For Generating Hematopoietic Stem Cell Populations, Gary Van Zant, Ying Liang

Toxicology and Cancer Biology Faculty Patents

Various embodiments provide methods and related compositions for increasing the population size of hematopoietic stem cells (HSCs) in patients that may benefit from reconstitution of stem cells and/or differentiated cells of the blood lineage. The present methods enable the production of HSCs ex vivo and in vivo by reducing latexin expression and/or latexin activity within HSC exposed to various antagonists. Inhibition of latexin expression and/or latexin activity by various antagonists can promote HSC proliferation and/or inhibit HSC apoptosis. Antagonists that can reduce latexin expression and/or latexin activity can be utilized to regenerate endogenous HSCs within patients affected with disorders, diseases, …

Elucidating The Mechanisms Underlying Alzheimer's Disease-Associated Genetic Polymorphisms, Steven Estus

Sanders-Brown Center on Aging Presentations

Recent genome-wide association studies (GWAS) have yielded a bounty of single nucleotide polymorphisms (SNP)s related to Alzheimer's disease (AD) or conditions associated with AD. Here, we will present several vignettes that illustrate approaches to use these results to clarify AD-related pathways and potential therapeutics

Efficacy And Safety Characteristics Of Mometasone Furoate/Formoterol Fumarate Fixed-Dose Combination In Subjects With Moderate To Very Severe Copd: Findings From Pooled Analysis Of Two Randomized, 52-Week Placebo-Controlled Trials, Donald P. Tashkin, Dennis E. Doherty, Edward Kerwin, Carlos E. Matiz-Bueno, Barbara Knorr, Tulin Shekar, Davis Gates, Heribert Staudinger

Internal Medicine Faculty Publications

Background:

The clinical efficacy and safety of a mometasone furoate/formoterol fumarate (MF/F) fixed-dose combination formulation administered via a metered-dose inhaler was investigated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD).

Methods:

Two 52-week, multicenter, double-blind, placebo-controlled trials with identical study designs were conducted in current or ex-smokers (aged =40 years), and pooled study results are presented herein. Subjects (n = 2251) were randomized to 26 weeks of twice-daily treatment with MF/F 400/10 µg, MF/F 200/10 µg, MF 400 µg, F 10 µg, or placebo. After the 26-week treatment period, placebo subjects completed the trial and 75% …

Effects Of Mometasone Furoate/Formoterol Fumarate Fixed-Dose Combination Formulation On Chronic Obstructive Pulmonary Disease (Copd): Results From A 52-Week Phase Iii Trial In Subjects With Moderate-To-Very Severe Copd, Dennis E. Doherty, Donald P. Tashkin, Edward Kerwin, Barbara Knorr, Tulin Shekar, Sibabrata Banerjee, Heribert Staudinger

Internal Medicine Faculty Publications

RATIONALE: The purpose of this study was to investigate the clinical efficacy and safety of a fixed-dose combination of mometasone furoate/formoterol fumarate (MF/F) administered via a metered-dose inhaler in subjects with moderate-to-very severe chronic obstructive pulmonary disease (COPD).

METHODS: This multicenter, double-blind, placebo-controlled trial had a 26-week treatment period and a 26-week safety extension. Subjects (n = 1196), at least 40 years old, were current or ex-smokers randomized to twice-daily inhaled MF/F 400/10 μg, MF/F 200/10 μg, MF 400 μg, F 10 μg, or placebo. The trial's co-primary endpoints were mean changes from baseline, as area under the curve (AUC), …

Efficacy And Safety Characteristics Of Mometasone Furoate/Formoterol Fumarate Fixed-Dose Combination In Subjects With Moderate To Very Severe Copd: Findings From Pooled Analysis Of Two Randomized, 52-Week Placebo-Controlled Trials, Donald P. Tashkin, Dennis E. Doherty, Edward Kerwin, Carlos E. Matiz-Bueno, Barbara Knorr, Tulin Shekar, Sibabrata Banerjee, Heribert Staudinger

Internal Medicine Faculty Publications

Background: A clinical trial of mometasone furoate/formoterol fumarate (MF/F) administered via a metered-dose inhaler in subjects with moderate to very severe chronic obstructive pulmonary disease (COPD) investigated the efficacy and safety of a fixed-dose combination of MF/F.

Methods: This multicenter, double-blind, placebo-controlled trial had a 26-week treatment period and a 26-week safety extension. Subjects (n = 1055; ≥40 years) were current or ex-smokers randomized to twice-daily treatment with inhaled MF/F 400/10 µg, MF/F 200/10 µg, MF 400 µg, F 10 µg, or placebo. The coprimary endpoints of the trial were mean changes from baseline in forced expiratory volume in 1 …

Tricuspid Annular Plane Systolic Excursion (Tapse) Revisited Using Cmr, Srinivas L. Naik, Jeffrey J. Rodriguez, Nishant Kalra, Vincent L. Sorrell

Internal Medicine Presentations

This observational pilot project was performed as background to eventually create a rapid, automated and accurate assessment of RV systolic function in variable clinical subgroups. We propose new parameters that characterize the global systolic function of the right ventricle with a simple linear measurement.

A Method To Determine Regional Mechanical Left Ventricular Dyssynchrony Based On High Temporal Resolution Short Axis Ssfp Cine Images, Jonathan Suever, Brandon K. Fornwalt, Michael Lloyd, John N. Oshinski

Pediatrics Presentations

Left ventricular (LV) mechanical dyssynchrony has been proposed as a parameter to select patients for cardiac resynchronization therapy (CRT) [Bax et al JACC 2005].Several recent studies have shown that placing the LV pacing lead in the most delayed regions yields a better response to CRT [Ansalone et al JACC 2002]. However, most imaging-based methods assess global LV dyssynchrony providing a single value for the entire LV. Regional maps of LV dyssynchrony are required for planning LV lead placement.

The objective of this study was to develop a method to create a map of regional left ventricular mechanical dyssynchrony based on …

Characterization Of The Size And Location Of Dyssynchronous Regions In Patients Undergoing Crt, Jonathan Suever, Brandon K. Fornwalt, Michael Lloyd, John N. Oshinski

Pediatrics Presentations

The amount and location of left ventricular (LV) mechanical dyssynchrony affects an individual’s ability to respond positively to cardiac resynchronization therapy (CRT) [Bax et al JACC 2005]. By using high temporal resolution short-axis cines, it is possible to derive radial motion curves throughout the LV. These radial motion curves can be used to create maps showing dyssynchronous regions in patients enrolled for CRT.

The objective of this study was to characterize the size and location of areas of mechanical dyssynchrony in patients scheduled for CRT by comparing their radial wall motion curves to radial motion curves from normal subjects.

Psychosis And Smoking Cessation: Difficulties In Quitting Associated With Sex And Substance Abuse, Ana González-Pinto, Susana Alberich, Sonia Ruiz De Azúa, Mónica Martínez-Cengotitabengoa, Miryan Fernández, Miguel Gutiérrez, Margarita Saenz, Ariadna Besga, Paloma Galdós, Jose De Leon

Psychiatry Faculty Publications

No prospective studies of first psychotic episodes have explored sex differences in smoking cessation. The aim of this study was to determine the influence of sex and substance abuse on smoking cessation during an 8-year follow-up of patients after a first psychotic episode. Logistic regression modeling was used to identify factors associated with smoking cessation by sex. To examine for sex variable interactions, the following two methods were used: 1) for other clinical variables, mixed analyses were calculated; and 2) for use of other substances, logistic regression models were performed only in the substance users. At baseline, 79% of men …

Can The Holmes-Rahe Social Readjustment Rating Scale (Srrs) Be Used As A Suicide Risk Scale? An Exploratory Study, Hilario Blasco-Fontecilla, David Delgado-Gomez, Teresa Legido-Gil, Jose De Leon, M. Mercedes Perez-Rodriguez, Enrique Baca-Garcia

Psychiatry Faculty Publications

The objective of this research was to examine whether the Holmes-Rahe Social Readjustment Rating Scale, a life event scale, can be used to identify suicide attempters. The Holmes-Rahe Social Readjustment Rating Scale's ability to identify suicide attempters was tested in 1183 subjects (478 suicide attempters, 197 psychiatric inpatients, and 508 healthy controls) using the Fisher Linear Discriminant Analysis and traditional psychometric methods. The Fisher Linear Discriminant Analysis outperformed traditional psychometric approaches (area under the curve: 0.85 vs. 0.78; p < 0.05) and indicated that this scale may be used to identify suicide attempters. The life events that better characterized suicide attempters were change in frequency of arguments, marital separation, and personal injury. The Holmes-Rahe Social Readjustment Rating Scale may help identify suicide attempters.

Longitudinal Impact Of The Project Paths On Adolescent Risk Behavior: What Happened After Five Years?, Daniel T. L. Shek, Lu Yu

Pediatrics Faculty Publications

The present study investigated the longitudinal impact of the Project PATHS, a large-scale curriculum-based positive youth development program in Hong Kong, on the development of adolescents' risk behavior over a period of five years. Using a longitudinal randomized controlled design, eight waves of data were collected from 19 experimental schools in which students participated in the Project PATHS (N = 2,850 at Wave 8) and 24 control schools without joining the Project PATHS (N = 3,640 at Wave 8). At each wave, students responded to measures assessing their current risk behaviors, including delinquency, use of different types of drug, and …

Predictors Of Survival In A Cohort Of Patients With Polymyositis And Dermatomyositis: Effect Of Corticosteroids, Methotrexate And Azathioprine, Elena Schiopu, Kristine Phillips, Paul M. Macdonald, Leslie J. Crofford, Emily C. Somers

Internal Medicine Faculty Publications

INTRODUCTION: The idiopathic inflammatory myopathies are rare diseases for which data regarding the natural history, response to therapies and factors affecting mortality are needed. We performed this study to examine the effects of treatment and clinical features on survival in polymyositis and dermatomyositis patients.

METHODS: A total of 160 consecutive patients (77 with polymyositis and 83 with dermatomyositis) seen at the University of Michigan from 1997 to 2003 were included. Medical records were abstracted for clinical, laboratory and therapeutic data, including initial steroid regimen and immunosuppressive use. State vital records were utilized to derive mortality and cause of death data. …

Enantioselective Synthesis Of (+) And (–)-2-[1-(2,6-Dichlorophenoxy)-Ethyl]-1,3-Diazacyclopent-2-Ene, Peter A. Crooks, Ashish Pramod Vartak

Pharmaceutical Sciences Faculty Patents

Methods for the enantioselective synthesis of (+) and (−) lofexidine or 2-[1-(2,6)-dichlorophenoxy)-ethyl]-1,3-diazacyclopent-2-ene involve converting (+) or (−) 1-methyl-1-[2,6-dichlorophenoxy]ethanamide to an (+) or (−) imino-ether intermediate by electrophilic attack of the amide oxygen by a trimethoxonium ion and, without isolation, converting the (+) or (−) imino-ether intermediate to (+) or (−) 2-[1-(2,6-dichlorophenoxy)-ethyl]1,3-diazacyclopent-2-ene by adding ethylene diamine; and optionally converting the (+) or (−) 2-[1-(2,6-dichlorophenoxy)-ethyl]1,3-diazacyclopent-2-ene into a pharmaceutically acceptable acid addition salt thereof.

A Spatial Cluster Analysis Of Tractor Overturns In Kentucky From 1960 To 2002, Daniel M. Saman, Henry P. Cole, Agricola Odoi, Melvin L. Myers, Daniel I. Carey, Susan C. Westneat

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: Agricultural tractor overturns without rollover protective structures are the leading cause of farm fatalities in the United States. To our knowledge, no studies have incorporated the spatial scan statistic in identifying high-risk areas for tractor overturns. The aim of this study was to determine whether tractor overturns cluster in certain parts of Kentucky and identify factors associated with tractor overturns.

METHODS: A spatial statistical analysis using Kulldorff's spatial scan statistic was performed to identify county clusters at greatest risk for tractor overturns. A regression analysis was then performed to identify factors associated with tractor overturns.

RESULTS: The spatial analysis …

Method For Screening For A Tobiano Coat Color Genotype, Ernest Bailey, Samantha A. Brooks

Veterinary Science Faculty Patents

A method for screening for a Tobiano genotype includes obtaining a nucleic acid from an equine animal, and analyzing the nucleic acid for the presence of an inversion in a chromosome ECA3q which is indicative of the genotype for Tobiano. The method includes detecting at least one of a telomeric breakpoint of an inverted ECA3q chromosome and/or a centromeric breakpoint of an inverted ECA3q chromosome. In one embodiment, the nucleic acid may be analyzed by the steps of hybridizing the group of probes or primers having the sequences set forth herein in SEQ ID NO:8, SEQ ID NO: 9, and …

Public Health Services And Systems Research, F. Douglas Scutchfield Md

Preventive Medicine and Environmental Health Presentations

No abstract provided.

National Longitudinal Survey Of Public Health Systems: 2011-2012 Wave, Public Health Practice-Based Research Networks

Health Management and Policy Reports

Since 1998, researchers have followed a nationally representative cohort of U.S. communities to examine the types of public health activities performed within the community, the range of organizations contributing to each activity, and the perceived effectiveness of each activity in addressing community needs. This information, obtained through a validated survey of local public health officials, provides an in-depth view of the structure and function of local public health delivery systems and how these systems evolve over time. Originally conducted with support from the U.S. Centers for Disease Control and Prevention, the National Longitudinal Survey of Public Health Systems (NLSPHS) was …

A High Density Snp Array For The Domestic Horse And Extant Perissodactyla: Utility For Association Mapping, Genetic Diversity, And Phylogeny Studies, Molly E. Mccue, Danika L. Bannasch, Jessica L. Petersen, Jessica Gurr, Ernie Bailey, Matthew M. Binns, Ottmar Distl, Gérard Guérin, Telhisa Hasegawa, Emmeline W. Hill, Tosso Leeb, Gabriella Lindgren, M Cecilia T. Penedo, Knut H. Røed, Oliver A. Ryder, June E. Swinburne, Teruaki Tozaki, Stephanie J. Valberg, Mark Vaudin, Kerstin Lindblad-Toh, Claire M. Wade, James R. Mickelson

Veterinary Science Faculty Publications

An equine SNP genotyping array was developed and evaluated on a panel of samples representing 14 domestic horse breeds and 18 evolutionarily related species. More than 54,000 polymorphic SNPs provided an average inter-SNP spacing of ∼43 kb. The mean minor allele frequency across domestic horse breeds was 0.23, and the number of polymorphic SNPs within breeds ranged from 43,287 to 52,085. Genome-wide linkage disequilibrium (LD) in most breeds declined rapidly over the first 50-100 kb and reached background levels within 1-2 Mb. The extent of LD and the level of inbreeding were highest in the Thoroughbred and lowest in the …