Medicine and Health Sciences Commons^™

Successfully Climbing The "Stairs": Surmounting Failed Translation Of Experimental Ischemic Stroke Treatments, Michael Kahle, Gregory J. Bix

Sanders-Brown Center on Aging Faculty Publications

The Stroke Therapy Academic Industry Roundtable (STAIR) provided initial (in 1999) and updated (in 2009) recommendations with the goal of improving preclinical stroke therapy assessment and to increase the translational potential of experimental stroke treatments. It is important for preclinical stroke researchers to frequently consider and revisit these concepts, especially since promising experimental stroke treatments continue to fail in human clinical trials. Therefore, this paper will focus on considerations for several key aspects of preclinical stroke studies including the selection and execution of the animal stroke model, drug/experimental treatment administration, and outcome measures to improve experimental validity and translation potential. …

Human Calmodulin Methyltransferase: Expression, Activity On Calmodulin, And Hsp90 Dependence, Sophia Magen, Roberta Magnani, Sitvanit Haziza, Eli Hershkovitz, Robert Houtz, Franca Cambi, Ruti Parvari

Horticulture Faculty Publications

Deletion of the first exon of calmodulin-lysine N-methyltransferase (CaM KMT, previously C2orf34) has been reported in two multigene deletion syndromes, but additional studies on the gene have not been reported. Here we show that in the cells from 2p21 deletion patients the loss of CaM KMT expression results in accumulation of hypomethylated calmodulin compared to normal controls, suggesting that CaM KMT is essential for calmodulin methylation and there are no compensatory mechanisms for CaM methylation in humans. We have further studied the expression of this gene at the transcript and protein levels. We have identified 2 additional …

Use Of The County Health Rankings By Local Health Departments In Florida, 2010 - 2011, Nancy L. Winterbauer, Bonita Sorensen, James B. Tidwell

Frontiers in Public Health Services and Systems Research

This paper describes how local health departments (LHDs) in Florida used the County Health Rankings over the first two years of their release (2010 – 2011). We surveyed LHD leadership to describe if, how and to what extent the Rankings were used by Florida’s 67 LHDs to improve the health of their communities and describe changes in use from the 2010 to the 2011 release. Our results indicate substantial use of the Rankings by Florida’s LHDs, particularly as applied to community health assessments, staff education, as a starting point for examining other indicators and databases, and in grant applications. From …

Effectiveness And Challenges For Implementing Quality Improvement Activities In Nebraska’S Local Health Departments, Li-Wu Chen, Anh Nguyen, Janelle J. Jacobson, Diptee Ojha, David Palm

Frontiers in Public Health Services and Systems Research

What is already known on this topic? Although the implementation strategies and effectiveness of quality improvement (QI) activities have been examined extensively for many industries, including the health care sector, very few studies have focused on QI activities in the public health context.

What is added by this report? The study results indicated that Nebraska’s LHDs still face significant barriers for QI implementation, including low capacity, knowledge gaps, inadequate resources, and low institutional QI maturity.

What are the implications for public health practice/policy/research? Policy makers and LHDs should provide QI training and external QI expertise to LHD staff and better …

Building Capacity To Support And Study Qi In Local Georgia Public Health Systems, William C. Livingood, Nandi Marshall, Angela Peden, Ketty Gonzales, Gulzar H. Shah, Russ Toal, Kellie Penix, Dayna Alexander, Kay Davis, Sylvester Nixon, Purity Cummings, William Riley, Lynn Woodhouse

Frontiers in Public Health Services and Systems Research

The study of quality improvement within Georgia’s local public health systems provides important insight into the use of regional bodies as quality improvement (QI) collaboratives and multijurisdictional entities. This report describes QI initiatives following a RWJF funded quick strike research grant to assess health district capacity to conduct QI in Georgia’s local public health systems. These QI initiatives use QI to improve public health outcomes including: Adolescent pregnancy and Sexually Transmitted Infection prevention, HIV prevention and control, and HIV Management.

Tax Levy Financing For Local Public Health: Relationships Between Fiscal Allocation, Fiscal Effort And Fiscal Capacity, William Riley, Kim J. Gearin, Carmen D. Parrotta, Jill Briggs, M. Elizabeth Gyllstrom

Frontiers in Public Health Services and Systems Research

This study examines property tax levy (local tax levy) as a source of local health department (LHD) funding during a five year period (2006-2010) in all Minnesota counties by assessing fiscal effort, fiscal allocation and fiscal capacity. Local health departments rely on pluralistic funding from local, state, federal and private sources. However, local tax levy funding is unexplored and little is known regarding the extent of fiscal allocation (tax levy used for LHD), fiscal effort (potential amount of tax levy available for LHD), and fiscal capacity (wealth of community). More important it is not known to what extent variation between …

Mandated Activities And Limited Decision-Making Authority Among Local Public Health Officials, Betty Bekemeier, Anthony L-T Chen, Nami Kawakyu

Frontiers in Public Health Services and Systems Research

Local public health department leaders face difficult decisions regarding the allocation of increasingly scarce resources, yet existing evidence for public health decision making, while still limited, is underutilized by public health officials. Participants in this study described processes regarding resource allocation in response to local budget cuts as based largely on legally mandated activities and categorical funding and perceived these factors as limiting much of their agency-level decision making to a relatively small portion of flexible funding. In the limited areas in which they perceived themselves to have flexibility, they generally considered their agencies to have very little capacity for …

Evidence-Based Decision Making In Local Health Departments, Linda Weiss, Collette Sosnowy, Christopher M. Maylahn, Nancy J. Katagiri, Sylvia Pirani

Frontiers in Public Health Services and Systems Research

Evidence-based decision making (EBDM) represents an important strategy to increase efficacy and efficiency of public health programs and practice. There is insufficient information on the application of EBDM among local health departments (LHDs). This qualitative study examined use of EBDM in New York State (NYS) LHDs and factors facilitating and impeding its adoption through interviews and focus groups with 47 LHD commissioners, health directors, and other upper-level staff. Findings suggest variability in application of EBDM in NYS LHDs. A number of internal factors (e.g., staff capacity, organizational culture) and external factors (e.g., policy environment, appropriate and …

From The Frontier: Translating Research To Practice, Paul C. Erwin

Frontiers in Public Health Services and Systems Research

The purpose of this invited article is to describe the process of translating research into public health practice. An example is provided, showing how questions arose in the practice setting, a researcher was identified to help answer the questions, and findings from the research were applied in the practice setting. In this example, Dr. Lea LaFave (Community Health Institute/JSI in New Hampshire) worked with Dr. Danielle Varda (Assistant Professor at the University of Colorado/ Denver, School of Public Affairs) to use social network analysis to better understand a network of coalitions focused on underage substance abuse. The social network analysis …

Stimulating Public Health Improvement In Complex And Constrained Delivery Systems: Findings From The Public Health Pbrns, Glen P. Mays

Frontiers in Public Health Services and Systems Research

The Robert Wood Johnson Foundation’s Public Health Practice-Based Research Networks Program sponsored a series of studies to examine how public health decision-makers are responding to accreditation, quality improvement, and public reporting initiatives amid the ongoing fiscal pressures. Overall, the evidence to date indicates that these initiatives represent promising strategies for strengthening evidence-based decision-making and expanding the delivery of evidence-tested programs and policies in local public health settings. Continued, comparative research and evaluation activities are needed to provide more definitive evidence about which combination of strategies work best, for which population groups, in which community and organizational settings, and why.

Multiple Regulatory Mechanisms Control B-1 B Cell Activation, Vishal Sindhava, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

B-1 cells constitute a unique subset of B cells identified in several species including mice and humans. B-1 cells are further subdivided into B-1a and B-1b subsets as the former but not the later express CD5.The B-1a subset contributes to innate type of immune responses while the B-1b B cell subset contributes to adaptive responses. B-1 cell responses to B cell receptor (BCR) as well as Toll-like receptor (TLR) ligation are tightly regulated due to the cross-reactivity of antigen specific receptors on B-1 cells to self-antigens. B-1 cells are elevated in several autoimmune diseases. CD5 plays a major role in …

Global Profiling Of Alternative Splicing Events And Gene Expression Regulated By Hnrnph/F, Erming Wang, Vahid Aslanzadeh, Filomena Papa, Haiyan Zhu, Pierre De La Grange, Franca Cambi

Neurology Faculty Publications

In this study, we have investigated the global impact of heterogeneous nuclear Ribonuclear Protein (hnRNP) H/F-mediated regulation of splicing events and gene expression in oligodendrocytes. We have performed a genome-wide transcriptomic analysis at the gene and exon levels in Oli-neu cells treated with siRNA that targets hnRNPH/F compared to untreated cells using Affymetrix Exon Array. Gene expression levels and regulated exons were identified with the GenoSplice EASANA algorithm. Bioinformatics analyses were performed to determine the structural properties of G tracts that correlate with the function of hnRNPH/F as enhancers vs. repressors of exon inclusion. Different types of alternatively spliced events …

Elevated Cardiovascular Risk Among Adults With Obstructive And Restrictive Airway Functioning In The United States: A Cross-Sectional Study Of The National Health And Nutrition Examination Survey From 2007 - 2010, Earl S. Ford, Ann G. Wheaton, David M. Mannino, Latitia Presley-Cantrell, Chaoyang Li, Janet B. Croft

David M. Mannino

Background

Reasons for the excess risk for cardiovascular disease among people with chronic obstructive pulmonary disease remain unclear. Our objective was to examine the cardiovascular risk profile for adults with obstructive and restrictive impairments of lung functioning in a representative sample of adults from the United States.

Methods

We used data from adults aged 20–79 years who participated in the National Health and Nutrition Examination Survey from 2007 to 2010 and had a pulmonary function test. The severity of obstructive impairment was defined by adapting the Global Initiative for Chronic Obstructive Lung Disease criteria.

Results

Among 7249 participants, 80.9% had …

Elevated Cardiovascular Risk Among Adults With Obstructive And Restrictive Airway Functioning In The United States: A Cross-Sectional Study Of The National Health And Nutrition Examination Survey From 2007-2010, Earl S. Ford, Anne G. Wheaton, David M. Mannino, Letitia Presley-Cantrell, Chaoyang Li, Janet B. Croft

Preventive Medicine and Environmental Health Faculty Publications

BACKGROUND: Reasons for the excess risk for cardiovascular disease among people with chronic obstructive pulmonary disease remain unclear. Our objective was to examine the cardiovascular risk profile for adults with obstructive and restrictive impairments of lung functioning in a representative sample of adults from the United States.

METHODS: We used data from adults aged 20-79 years who participated in the National Health and Nutrition Examination Survey from 2007 to 2010 and had a pulmonary function test. The severity of obstructive impairment was defined by adapting the Global Initiative for Chronic Obstructive Lung Disease criteria.

RESULTS: Among 7249 participants, 80.9% had …

Treatment Of Klebsiella Pneumoniae Carbapenemase (Kpc) Infections: A Review Of Published Case Series And Case Reports, Grace C. Lee, David S. Burgess

Pharmacy Practice and Science Faculty Publications

The emergence of Klebsiella pneumoniae carbapenemases (KPCs) producing bacteria has become a significant global public health challenge while the optimal treatment remains undefined. We performed a systematic review of published studies and reports of treatment outcomes of KPC infections using MEDLINE (2001-2011). Articles or cases were excluded if one of the following was fulfilled: no individual patient data provided, no treatment regimen specified, no treatment outcome specified, report of colonization, or greater than three antibiotics were used to treat the KPC infection. Data extracted included patient demographics, site of infection, organism, KPC subtype, antimicrobial therapy directed at KPC-infection, and treatment …

Effects Of Exercise On Ampk Signaling And Downstream Components To Pi3k In Rat With Type 2 Diabetes, Shicheng Cao, Bowen Li, Xuejie Yi, Bo Chang, Beibei Zhu, Zhenzhen Lian, Zhaoran Zhang, Gang Zhao, Huili Liu, He Zhang

Barnstable Brown Diabetes Center Faculty Publications

Exercise can increase skeletal muscle sensitivity to insulin, improve insulin resistance and regulate glucose homeostasis in rat models of type 2 diabetes. However, the potential mechanism remains poorly understood. In this study, we established a male Sprague-Dawley rat model of type 2 diabetes, with insulin resistance and β cell dysfunction, which was induced by a high-fat diet and low-dose streptozotocin to replicate the pathogenesis and metabolic characteristics of type 2 diabetes in humans. We also investigated the possible mechanism by which chronic and acute exercise improves metabolism, and the phosphorylation and expression of components of AMP-activated protein kinase (AMPK) and …

Luteolin Inhibits Human Prostate Tumor Growth By Suppressing Vascular Endothelial Growth Factor Receptor 2-Mediated Angiogenesis, Poyil Pratheeshkumar, Young-Ok Son, Amit Budhraja, Xin Wang, Songze Ding, Lei Wang, Andrew Hitron, Jeong-Chae Lee, Donghern Kim, Sasidharan Padmaja Divya, Gang Chen, Zhuo Zhang, Jia Luo, Xianglin Shi

Toxicology and Cancer Biology Faculty Publications

Angiogenesis, the formation of new blood vessels from pre-existing vascular beds, is essential for tumor growth, invasion, and metastasis. Luteolin is a common dietary flavonoid found in fruits and vegetables. We studied the antiangiogenic activity of luteolin using in vitro, ex vivo, and in vivo models. In vitro studies using rat aortic ring assay showed that luteolin at non-toxic concentrations significantly inhibited microvessel sprouting and proliferation, migration, invasion and tube formation of endothelial cells, which are key events in the process of angiogenesis. Luteolin also inhibited ex vivo angiogenesis as revealed by chicken egg chorioallantoic membrane assay (CAM) …

Public Health Return On Investment: Making The Case, Glen P. Mays

Health Management and Policy Presentations

Fiscal pressures and policy imperatives have created a need for rigorous economic analyses of public health programs and policies. ROI analyses can reveal whether the benefits of public health strategies justify their costs, who realizes these benefits and costs, and under what circumstances.

Comparative Effectiveness Research And Patient Centered Outcomes Research In Public Health Settings: Design, Analysis, And Funding Considerations, Glen P. Mays

Health Management and Policy Presentations

The principles and methods of CER and PCOR have developed primarily with therapeutics in mind, but they must also be applied to the study of public health programs, policies, and delivery systems. This session surveys the emerging field, and provides examples of CER/PCOR methods applied in public health settings using practice-based research networks (PBRNs).

Depletion Of Endothelial Or Smooth Muscle Cell-Specific Angiotensin Ii Type 1a Receptors Does Not Influence Aortic Aneurysms Or Atherosclerosis In Ldl Receptor Deficient Mice, Debra L. Rateri, Jessica J. Moorleghen, Victoria Knight, Anju Balakrishnan, Deborah A. Howatt, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Whole body genetic deletion of AT1a receptors in mice uniformly reduces hypercholesterolemia and angiotensin II-(AngII) induced atherosclerosis and abdominal aortic aneurysms (AAAs). However, the role of AT1a receptor stimulation of principal cell types resident in the arterial wall remains undefined. Therefore, the aim of this study was to determine whether deletion of AT1a receptors in either endothelial cells or smooth muscle cells influences the development of atherosclerosis and AAAs.

METHODOLOGY/PRINCIPAL FINDINGS: AT1a receptor floxed mice were developed in an LDL receptor -/- background. To generate endothelial or smooth muscle cell specific deficiency, AT1a receptor floxed mice were bred with …

The P2y(12) Antagonists, 2mesamp And Cangrelor, Inhibit Platelet Activation Through P2y(12)/G(I)-Dependent Mechanism, Binggang Xiang, Guoying Zhang, Hongmei Ren, Manjula Sunkara, Andrew J. Morris, T. Kent Gartner, Susan S. Smyth, Zhenyu Li

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: ADP is an important physiological agonist that induces integrin activation and platelet aggregation through its receptors P2Y(1) (Gα(q)-coupled) and P2Y(12) (Gα(i)-coupled). P2Y(12) plays a critical role in platelet activation and thrombosis. Adenosine-based P2Y(12) antagonists, 2-methylthioadenosine 5'-monophosphate triethylammonium salt hydrate (2MeSAMP) and Cangrelor (AR-C69931MX) have been widely used to demonstrate the role of P2Y(12) in platelet function. Cangrelor is being evaluated in clinical trials of thrombotic diseases. However, a recent study reported that both 2MeSAMP and Cangrelor raise intra-platelet cAMP levels and inhibit platelet aggregation through a P2Y(12)-independent mechanism.

METHODOLOGY/PRINCIPAL FINDINGS: The present work, using P2Y(12) deficient mice, sought to …

Understanding And Treating Smoking Among Individuals With A Mental Illness, Chizimuzo T.C. Okoli

Nursing Presentations

• Background and significance

• Reasons for smoking among individuals living with a mental illness

• Smoking cessation treatment for individuals living with a mental illness

Transforming The Healthcare Response To Intimate Partner Violence And Taking Best Practices To Scale, Michele R. Decker, Shannon Frattaroli, Brigid Mccaw, Ann L. Coker, Elizabeth Miller, Phyllis Sharps, Wendy G. Lane, Mahua Mandal, Kelli Hirsch, Donna M. Strobino, Wendy L. Bennett, Jacquelyn Campbell, Andrea Gielen

CRVAW Faculty Journal Articles

BACKGROUND: Intimate partner violence (IPV) is prevalent among adolescent and adult women, with significant physical, sexual, and mental health consequences. In 2011, the Institute of Medicine's Clinical Preventive Services for Women consensus report recommended universal screening for violence as a component of women's preventive services; this policy has been adopted by the Health Resources and Services Administration (HRSA). These policy developments require that effective clinic-based interventions be identified, easily implemented, and taken to scale.

METHODS: To foster dialogue about implementing effective interventions, we convened a symposium entitled "Responding to Violence Against Women: Emerging Evidence, Implementation Science, and Innovative Interventions," on …

Occupational Chronic Obstructive Pulmonary Disease: An Update, Enrique Diaz-Guzman, David M. Mannino, Shambhu Aryal

David M. Mannino

Chronic obstructive pulmonary disease represents a major cause of morbidity and mortality in industrialized and nonindustrialized countries. Although tobacco use remains the main factor associated with development of the disease, occupational risk factors represent an important and preventable cause. The most common occupationally related factors include exposure to organic dusts, metallic fumes, and a variety of other mineral gases and/or vapors. This article summarizes the literature on the subject and provides an update of the most recent advances in the field.

Epidemiology Of Comorbidities In Chronic Obstructive Pulmonary Disease: Clusters, Phenotypes And Outcomes, Shambhu Aryal, Enrique Diaz-Guzman, David M. Mannino

David M. Mannino

COPD is a complex multisystem disease often accompanied by multiple co-morbidities that contribute to symptoms, exacerbations, hospital admissions and mortality. Individual comorbidities can be grouped into clusters of common human pathology: inflammation/immune response (e.g., ischemic heart disease, metabolic syndrome), thrombosis/hemorrhage (e.g., cerebrovascular diseases, pulmonary embolism), fibrosis/cell proliferation (e.g., lung cancer and other malignancies) and apoptosis/necrosis (e.g., osteoporosis, skeletal muscle dysfunction). While the prevalence of the co-morbidities has been described in a number of observational studies, there is considerable variability in results; moreover characterization of cluster of co-morbidities with the most clinical significance in terms of morbidity and mortality is still …

Drug Overdose Morbidity And Mortality In Kentucky, 2000-2010: An Examination Of Statewide Data, Including The Rising Impact Of Prescription Drug Overdose On Fatality Rates, And The Parallel Rise In Associated Medical Costs, Terry Bunn, Svetla Slavova

Kentucky Injury Prevention and Research Center Special Report

From Foreword:

Kentucky has seen an explosion in fatal poisonings, particularly prescription drug related fatalities, in the last decade. In 2009, Kentucky had the 5^th highest drug overdose rate in the US, increased from the 6^th highest drug overdose fatality rate determined in 2008 (CDC WONDER). Kentucky also had the 5^th highest nonmedical use of opioid pain relievers, and 11^th highest for opioid pain reliever sales in the nation (CDC, MMWR Report November 4, 2011). These drug overdose mortality statistics are extremely startling and only begin to reveal the devastating mental, emotional, and economic toll and …

Fak Is A Critical Regulator Of Neuroblastoma Liver Metastasis, Sora Lee, Jingbo Qiao, Pritha Paul, Kathleen L. O'Connor, B. Mark Evers, Dai H. Chung

Surgery Faculty Publications

Neuroblastomas express increased levels of gastrin-releasing peptide receptor (GRP-R). However, the exact molecular mechanisms involved in GRP-R-mediated cell signaling in neuroblastoma growth and metastasis are unknown. Here, we report that focal adhesion kinase (FAK), as a critical downstream target of GRP-R, is an important regulator of neuroblastoma tumorigenicity. We found that FAK expression correlates with GRP-R expression in human neuroblastoma sections and cell lines. GRP-R overexpression in SK-N-SH cells increased FAK, integrin α3 and β1 expressions and cell migration. These cells demonstrated flatter cell morphology with broad lamellae, in which intense FAK expression was localized to the leading edges of …

Anti-Cocaine Compositions And Treatment, Donald W. Landry, Joanne Macdonald, Shi-Xiang Deng, Chang-Guo Zhan, Daquan Gao, James H. Woods, Roger K. Sunahara, Diwahar L. Narasimhan, Victor Yang, Mei-Chuan Holden Ko, John J. Tesmer, Tien-Yi Lee, Young Min Kwon

Pharmaceutical Sciences Faculty Patents

Embodiments of the invention disclosed herein generally relate to anti-cocaine therapeutics. Specifically, some embodiments of the invention relate to highly efficient, thermostable, and long-lasting cocaine esterase (CocE) mutants that can protect against the toxic and reinforcing effects of cocaine in subjects. Provided herein are mutant CocE polypeptides displaying thermostable esterase activity. Also provided are methods of treating cocaine-induced conditions in a subject in need via administration of mutant CocE as well as methods for high-throughput screening of candidate esterase polypeptides.

Lack Of P53 Affects The Expression Of Several Brain Mitochondrial Proteins: Insights From Proteomics Into Important Pathways Regulated By P53, Ada Fiorini, Rukhsana Sultana, Eugenio Barone, Giovanna Cenini, Marzia Perluigi, Cesare Mancuso, Jian Cai, Jon B. Klein, Daret K. St. Clair, D. Allan Butterfield

Chemistry Faculty Publications

The tumor suppressor protein p53 has been described "as the guardian of the genome" for its crucial role in regulating the transcription of numerous genes responsible for cells cycle arrest, senescence, or apoptosis in response to various stress signals. Although p53 promotes longevity by decreasing the risk of cancer through activation of apoptosis or cellular senescence, several findings suggest that an increase of its activity may have deleterious effects leading to selected aspects of the aging phenotype and neurodegenerative diseases. There is the link between p53 and oxidative stress, the latter a crucial factor that contributes to neurodegenerative processes like …

Cyclooxygenase-2 Inhibition Attenuates Abdominal Aortic Aneurysm Progression In Hyperlipidemic Mice, Sarbani Ghoshal, Charles D Loftin

Pharmaceutical Sciences Faculty Publications

Abdominal aortic aneurysms (AAAs) are a chronic inflammatory disease that increase the risk of life-threatening aortic rupture. In humans, AAAs have been characterized by increased expression of cyclooxygenase-2 and the inactivation of COX-2 prior to disease initiation reduces AAA incidence in a mouse model of the disease. The current study examined the effectiveness of selective cyclooxygenase-2 (COX-2) inhibition on reducing AAA progression when administered after the initiation of AAA formation. AAAs were induced in hyperlipidemic apolipoprotein E-deficient mice by chronic angiotensin II (AngII) infusion and the effect of treatment with the COX-2 inhibitor celecoxib was examined when initiated at different …