Medicine and Health Sciences Commons^™

Epigenetic Dominance Of Prion Conformers, Eri Saijo, Hae-Eun Kang, Jifeng Bian, Kristi G. Bowling, Shawn Browning, Sehun Kim, Nora Hunter, Glenn C. Telling

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Although they share certain biological properties with nucleic acid based infectious agents, prions, the causative agents of invariably fatal, transmissible neurodegenerative disorders such as bovine spongiform encephalopathy, sheep scrapie, and human Creutzfeldt Jakob disease, propagate by conformational templating of host encoded proteins. Once thought to be unique to these diseases, this mechanism is now recognized as a ubiquitous means of information transfer in biological systems, including other protein misfolding disorders such as those causing Alzheimer's and Parkinson's diseases. To address the poorly understood mechanism by which host prion protein (PrP) primary structures interact with distinct prion conformations to influence pathogenesis, …

Mismatch Repair Genes Mlh1 And Mlh3 Modify Cag Instability In Huntington's Disease Mice: Genome-Wide And Candidate Approaches, Ricardo Mouro Pinto, Ella Dragileva, Andrew Kirby, Alejandro Lloret, Edith Lopez, Jason St. Claire, Gagan B. Panigrahi, Caixia Hou, Kim Holloway, Tammy Gillis, Jolene R. Guide, Paula E. Cohen, Guo-Min Li, Christopher E. Pearson, Mark J. Daly, Vanessa C. Wheeler

Toxicology and Cancer Biology Faculty Publications

The Huntington's disease gene (HTT) CAG repeat mutation undergoes somatic expansion that correlates with pathogenesis. Modifiers of somatic expansion may therefore provide routes for therapies targeting the underlying mutation, an approach that is likely applicable to other trinucleotide repeat diseases. Huntington's disease Hdh(Q111) mice exhibit higher levels of somatic HTT CAG expansion on a C57BL/6 genetic background (B6.Hdh(Q111) ) than on a 129 background (129.Hdh(Q111) ). Linkage mapping in (B6x129).Hdh(Q111) F2 intercross animals identified a single quantitative trait locus underlying the strain-specific difference in expansion in the striatum, implicating mismatch repair (MMR) gene Mlh1 as the most likely candidate modifier. …

Lpa, Hgf, And Egf Utilize Distinct Combinations Of Signaling Pathways To Promote Migration And Invasion Of Mda-Mb-231 Breast Carcinoma Cells, Susan M. W. Harrison, Teresa Knifley, Min Chen, Kathleen L. O'Connor

Markey Cancer Center Faculty Publications

BACKGROUND: Various pathways impinge on the actin-myosin pathway to facilitate cell migration and invasion including members of the Rho family of small GTPases and MAPK. However, the signaling components that are considered important for these processes vary substantially within the literature with certain pathways being favored. These distinctions in signaling pathways utilized are often attributed to differences in cell type or physiological conditions; however, these attributes have not been systematically assessed.

METHODS: To address this question, we analyzed the migration and invasion of MDA-MB-231 breast carcinoma cell line in response to various stimuli including lysophosphatidic acid (LPA), hepatocyte growth factor …

New Oral Anticoagulants Are Not Superior To Warfarin In Secondary Prevention Of Stroke Or Transient Ischemic Attacks, But Lower The Risk Of Intracranial Bleeding: Insights From A Meta-Analysis And Indirect Treatment Comparisons, Partha Sardar, Saurav Chatterjee, Wen-Chih Wu, Edgar Lichstein, Joydeep Ghosh, Shamik Aikat, Debabrata Mukherjee

Internal Medicine Faculty Publications

PURPOSE: Patients with Atrial Fibrillation (AF) and prior stroke are classified as high risk in all risk stratification schemes. A systematic review and meta-analysis was performed to compare the efficacy and safety of New Oral Anticoagulants (NOACs) to warfarin in patients with AF and previous stroke or transient ischemic attack (TIA).

METHODS: Three randomized controlled trials (RCTs), including total 14527 patients, comparing NOACs (apixaban, dabigatran and rivaroxaban) with warfarin were included in the analysis. Primary efficacy endpoint was ischemic stroke, and primary safety endpoint was intracranial bleeding. Random-effects models were used to pool efficacy and safety data across RCTs. RevMan …

Public Health Services & Systems Research: Building The Science Of Public Health Delivery, Glen P. Mays

Health Management and Policy Presentations

The extreme heterogeneity in how public health activities are organized, financed, and implemented across U.S. states and communities provides compelling opportunities for research on the comparative effectiveness and efficiency of public health delivery. This talk highlights some of the most compelling and policy-relevant opportunities for research on public health organization and financing issues, and examines some of the ongoing studies in the field.

Preliminary Findings From An Interventional Study Using Network Analysis To Support Management In Local Health Departments In Florida, Chin S. Park, Hado Byon, Jonathan W. Keeling, Leslie M. Beitsch, Jacqueline A. Merrill

Frontiers in Public Health Services and Systems Research

Management is the core service that integrates and coordinates essential public health services. Managers of local health departments (LHDs) are experts in practice but may not have expertise in organizational management. We conducted an evidence-based training intervention in 10 LHDs in Florida to support managers’ decision-making on organizational integration and coordination. We deployed a standard survey to collect organizational network measurements pre and post intervention. We presented results as evidence-based performance feedback and interviewed managers to document how they used the results in the context of each organization. Post intervention we found unexpected, significantly higher network centralization in daily work. …

Characteristics Of A Local Health Department Associated With The Use Of The Health Equity Index, Moira A. Lawson, Sharon Mierzwa, Michael Knapp

Frontiers in Public Health Services and Systems Research

Local health departments are tasked with understanding and addressing health inequities in the populations they serve. To meaningfully address health inequities, local health departments have identified the need for credible local data to better understand the relationship between community conditions and health outcomes. Yet, when given access to these data, we observe a very large variation in the level of interest between local health departments.

In this study, we offered Connecticut’s Local health departments access to the Health Equity Index, a web based tool that provides data on health outcomes and community conditions at the state, municipal or neighborhood levels. …

Evaluating Use Of Custom Survey Reports By Local Health Departments, Nadya M. Belenky, Christine A. Bevc, Elizabeth Mahanna, Carol Gunther-Mohr, Mary V. Davis

Frontiers in Public Health Services and Systems Research

This report demonstrates how providing survey feedback, like comparative reports, to survey respondents can result in improvement activities. For each of the past three years (2010-2013), the North Carolina Institute for Public Health (NCIPH) has invited local health departments (LHDs) from 40 states to participate in a preparedness capacities survey. In addition, NCIPH fielded a six-question evaluation survey to a subset of LHDs (n=70) to determine how LHDs use these reports. LHDs that reported using their custom reports compared their preparedness capacities to other LHDs, conducted strategic planning (e.g., benchmarking, setting preparedness goals), planned staff trainings, and disseminated the report …

Assessing A Quality Improvement Project In A Georgia County Health Department, Dayna S. Alexander, William C. Livingood, Nandi A. Marshall, Angela Peden, Russ Toal, Gulzar H. Shah, Alesha Wright, Purity Cummings, Ketty Gonzalez, Lynn Woodhouse

Frontiers in Public Health Services and Systems Research

The study and evaluation of quality improvement among Georgia’s public health systems continues to be a major priority for the Georgia Public Health Practice Based Research Network (GAPH-PBRN). This article focuses on the application and evaluation of a Quality Improvement project in a Georgia County Health Department. The QI team sought to reduce the waiting time in the teen clinic; thereby, increasing the Quality Improvement culture one project at a time in this Health Department. The project revealed that Quality Improvement is a continuous process that requires change and adaptation by employees. This initial Quality Improvement project was the first …

The Relationship Between Quality Improvement And Health Information Technology Use In Local Health Departments, Kendra Johnson, Kim K. Nguyen, Shimin Zheng, Robin P. Pendley

Frontiers in Public Health Services and Systems Research

This research examined if there is a relationship between engagement in quality improvement (QI) and health information technology (HIT) for local health departments (LHDs) controlling for workforce, finance, population, and governance structure. This was a cross-sectional study that analyzed data obtained from the Core questions and Module 1 in the NACCHO 2010 Profile of LHDs. Descriptive statistics, bivariate analyses, and logistic regression analyses were conducted. Findings suggest that LHD engagement in QI has a relationship with utilization of HIT including electronic health records, practice management systems, and electronic syndromic surveillance systems. This study provides baseline information about the HIT use …

Commentary: The Road To Quality In Public Health, A Long But Important Journey, F. Douglas Scutchfield, Glen Mays, Marylou Wallace

Frontiers in Public Health Services and Systems Research

Quality improvement (QI) in public health departments is a focus in this sixth issue of Frontiers. Data is important to the development of quality improvement efforts. As we see growth of and meaningful use of electronic health records, the health department is in a position to take the lead as a data hub and to use this information wisely to both improve their QI efforts and link that QI to outcomes.

Autonomic Nervous System Function Following Prenatal Opiate Exposure, Matthew Todd Hambleton, Eric W. Reynolds, Thitinart Sithisarn, Stuart J. Traxel, Abhijit R. Patwardhan, Timothy N. Crawford, Marta S. Mendiondo, Henrietta S. Bada

Pediatrics Faculty Publications

In utero exposure to opiates may affect autonomic functioning of the fetus and newborn. We investigated heart rate variability (HRV) as a measure of autonomic stability in prenatal opiate-exposed neonates (n = 14) and in control term infants (n = 10). Electrocardiographic data during both non-nutritive and nutritive sucking were evaluated for RR intervals, heart rate (HR), standard deviation of the consecutive RR intervals (SDRR), standard deviation of the differences of consecutive RR intervals (SDDRR), and the power spectral densities in low and high frequency bands. In controls, mean HR increased significantly, 143-161 per min (p = …

Marijuana: Current Concepts, Donald E. Greydanus, Elizabeth K. Hawver, Megan M. Greydanus, Joav Merrick

Pediatrics Faculty Publications

Marijuana (cannabis) remains a controversial drug in the twenty-first century. This paper considers current research on use of Cannabis sativa and its constituents such as the cannabinoids. Topics reviewed include prevalence of cannabis (pot) use, other drugs consumed with pot, the endocannabinoid system, use of medicinal marijuana, medical adverse effects of cannabis, and psychiatric adverse effects of cannabis use. Treatment of cannabis withdrawal and dependence is difficult and remains mainly based on psychological therapy; current research on pharmacologic management of problems related to cannabis consumption is also considered. The potential role of specific cannabinoids for medical benefit will be revealed …

Firesetting In Childhood And Adolescence, Joav Merrick, Carrie Howell Bowling, Hatim A. Omar

Pediatrics Faculty Publications

Fire is the rapid oxidation of a material in the exothermic chemical process of combustion, releasing heat, light, and various reaction products. Fire is intriguing and therefore something that will attract a curious child from an early age.

In 2010, the United States fire department responded to 44,900 fires started by someone, usually a child, playing with fire. These fires caused 90 civilian deaths, 890 civilian injuries, and $210 million in direct property damage. Preschoolers and kindergartners are most likely to start these fires, while playing with matches or lighters and most likely to die in these fires. Most fire-play …

Human Sexuality And Adolescence, Joav Merrick, Ariel Tenenbaum, Hatim A. Omar

Pediatrics Faculty Publications

No abstract provided.

Release Of A Wound-Healing Agent From Plga Microspheres In A Thermosensitive Gel, H. A. Machado, J. J. Abercrombie, T. You, Patrick P. Deluca, K. P. Leung

Pharmaceutical Sciences Faculty Publications

The purpose of this research was to develop a topical microsphere delivery system in a thermosensitive 20% poloxamer 407 gel (Pluronic F127) to control release of KSL-W, a cationic antimicrobial decapeptide, for a period of 4-7 days for potential application in combat related injuries. KSL-W loaded microsphere formulations were prepared by a solvent extraction-evaporation method (water-oil-water), with poly (D,L-lactic-co-glycolic acid) (PLGA) (50 : 50, low-weight, and hydrophilic end) as the polymeric system. After optimization of the process, three formulations (A, B, and C) were prepared with different organic to water ratio of the primary emulsion while maintaining other components and …

Asthma And Risk Of Non-Respiratory Tract Infection: A Population-Based Case-Control Study, Duk Won Bang, Hyeon J Yang, Eell Ryoo, Majdi N. Al-Hasan, Brian Lahr, Larry M. Baddour, Barbara P. Yawn, Young J. Juhn

Internal Medicine Faculty Publications

OBJECTIVES: Asthmatics have increased risks of airway-related infections. Little is known about whether this is true for non-airway-related serious infections such as Escherichia coli bloodstream infection (BSI). We assessed whether asthma is associated with a risk of developing community-acquired E coli BSI.

DESIGN: The study was designed as a population-based retrospective case-control study.

SETTING: This population-based study was conducted in Olmsted County, Minnesota.

PARTICIPANTS: The study included 259 all eligible community-acquired E coli BSI cases in Olmsted County, MN between 1998 and 2007 and 259 birthday-matched, gender-matched and residency-matched controls.

PRIMARY AND SECONDARY OUTCOME MEASURES: Only community-acquired E coli BSI …

Bis-Pyridino Containing Compounds For The Use In The Treatment Of Cns Pathologies, Peter A. Crooks, Linda P. Dwoskin, Joshua Ayers, Vladimir Grinevich, Sangeetha Sumithran

Pharmaceutical Sciences Faculty Patents

N-n-Alkylation of nicotine converts nicotine from an agonist into an antagonist specifically for neuronal nicotinic acetylcholine receptor subtypes mediating nicotine-evoked dopamine release. Conformationally restricted analogs exhibit both high affinity and selectivity at this site, and are able to access the brain due to their ability to act as substrates for the blood-brain barrier choline transporter.

Diabetes And Prostate Cancer Screening In Black And White Men, Maureen Sanderson, Jay H. Fowke, Loren Lipworth, Xijing Han, Flora Ukoli, Ann L. Coker, William J. Blot, Margaret K. Hargreaves

CRVAW Faculty Journal Articles

PURPOSE: Prior studies conducted primarily among white men find a reduced risk of prostate cancer associated with time since developing diabetes. While biologic explanations are plausible, the association may in part arise from more frequent prostate cancer screening among those with a diabetes diagnosis. The purpose of the present study was to investigate the association between diabetes and prostate cancer screening.

METHODS: We examined differences in prostate cancer screening (prostate-specific antigen and/or digital rectal examination) testing practices after a diabetes diagnosis among lower-income persons living in the southeastern United States and enrolled in the Southern Community Cohort Study between 2002 …

Sexual Coercion And Sexual Violence At First Intercourse Associated With Sexually Transmitted Infections, Corrine M. Williams, Emily R. Clear, Ann L. Coker

CRVAW Faculty Journal Articles

BACKGROUND: Violence against women has been associated with subsequent risky sexual behaviors and sexually transmitted infections (STIs). We explored whether sexual coercion or violence at first intercourse was associated with self-reported STIs.

METHODS: Using nationally representative data from the 2006 to 2010 National Survey of Family Growth, we analyzed female respondents aged 18 to 44 (n = 9466) who answered questions on coercion at first intercourse (wantedness, voluntariness, and types of force used) and STIs using logistic regression analyses. We explored degrees of coercion, which we label as neither, sexual coercion (unwanted or nonphysical force), or sexual violence (involuntary or …

Turning The Tide On An Epidemic: A Native Kentuckian Changes The Deadly Trajectory Of Hiv Infection, Dannette Smith Cook

Ex-Patt Magazine

Interview: Dr. Mina Hosseinipour did not know her research would positively change the trajectory of the worldwide HIV epidemic when she graduated with a bachelor’s degree from the University of Kentucky in the early 1990’s.

Retinal Angiogenesis Suppression Through Small Molecule Activation Of P53, Sai H. Chavala, Younghee Kim, Laura Tudisco, Valeria Cicatiello, Till Milde, Nagaraj Kerur, Nidia Claros, Susan Yanni, Victor H. Guaiquil, William W. Hauswirth, John S. Penn, Shahin Rafii, Sandro De Falco, Thomas C. Lee, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

Neovascular age-related macular degeneration is a leading cause of irreversible vision loss in the Western world. Cytokine-targeted therapies (such as anti-vascular endothelial growth factor) are effective in treating pathologic ocular angiogenesis, but have not led to a durable effect and often require indefinite treatment. Here, we show that Nutlin-3, a small molecule antagonist of the E3 ubiquitin protein ligase MDM2, inhibited angiogenesis in several model systems. We found that a functional p53 pathway was essential for Nutlin-3-mediated retinal antiangiogenesis and disruption of the p53 transcriptional network abolished the antiangiogenic activity of Nutlin-3. Nutlin-3 did not inhibit established, mature blood vessels …

Suicide And Suicide Attempts In Kentucky, 2001‐2012, Joshua W. Lambert, Svetla Slavova

Kentucky Injury Prevention and Research Center Special Report

The data sources, methods, and definitions used in this report are based on the State Injury Indicators report: Instructions for Preparing 2011 Data, Atlanta, Georgia, March 2013, a publication of the National Center for Injury Prevention and Control, Centers for Disease Control and Prevention.

The Vancouver General Hospital Smoking Cessation Clinic: Outcomes From A Specialist Cessation Service Within Cardiology, Milan Khara, Chizimuzo T.C. Okoli

Nursing Presentations

PURPOSE: The purpose of our study is to examine pilot treatment outcomes of an outpatient Smoking Cessation Clinic (SCC) provided within Cardiology Services.

RELEVANCE/CONTEXT: Populations with cardiac conditions often continue to smoke at high rates (up to 62%), even after experiencing life-threatening cardiac events. Smoking cessation can greatly reduce the risk of further occurrence of a cardiac event and associated mortality. However few Cardiology services in Canada offer smoking cessation services and few Cardiologists refer smoking patients to such services. The Vancouver General Hospital’s SCC is housed within Cardiology Services and offers a longitudinal approach to smoking cessation. This …

Clinical Inertia In Type 2 Diabetes: A Retrospective Analysis Of Pharmacist-Managed Diabetes Care Vs. Usual Medical Care, Felix K. Yam, Aimee G. Adams, Holly Divine, Douglas Steinke, Mikael D. Jones

Pharmacy Practice and Science Faculty Publications

Background: Evidence suggests that patients with type 2 diabetes (T2DM) suffer from a high rate of “clinical inertia” or “recognition of the problem but failure to act.”

Objective: The aim of this study is to quantify the rate of clinical inertia between two models of care: Pharmacist-Managed Diabetes Clinic (PMDC) vs. Usual Medical Care (UMC).

Methods: Patients in a university based medical clinic with type 2 diabetes (T2DM) were analyzed in this retrospective cohort study. Patients were exposed to either PMDC or UMC. The difference in days to intervention in response to suboptimal laboratory values and time …

The Role Of Rehabilitation Following Autologous Chondrocyte Implantation: A Retrospective Chart Review, Jenny L. Toonstra, Jennifer Sebert Howard, Timothy L. Uhl, Robert A. English, Carl G. Mattacola

Physical Therapy Faculty Publications

PURPOSE/BACKGROUND: Clinical outcomes following autologous chondrocyte implantation (ACI) are influenced by multiple factors, including patient demographics, lesion characteristics, quality of the surgical repair, and post-operative rehabilitation. However, it is currently unknown what specific characteristics of rehabilitation have the greatest influence on clinical outcomes following ACI. The purpose of this study was to conduct a retrospective chart review of patients undergoing ACI with the intent to describe this patient population's demographics, clinical outcomes, and rehabilitation practices. This study aimed to assess the consistency of the documentation process relative to post-operative rehabilitation in order to provide information and guide initiatives for improving …

Cost Estimation Methods And Foundational Public Health Capabilities, Glen P. Mays

Health Management and Policy Presentations

The National Academy of Sciences Institute of Medine recently recommended that the federal government identify the components and costs of a "minimum package of public health services" and "foundational public health capabilities" that should be universally available across the U.S. This presentation reviews costing methods that can be used for identifying the costs required to establish "foundational public health capabilities" at state and local levels within the U.S. public health system.

Building The Science Of Delivery: Public Health Services & Systems Research, Glen P. Mays

Health Management and Policy Presentations

Studying variation and innovation in public health delivery can identify pathways for improving the organization, financing, and implementation of programs and policies that protect and promote health.

Proteomic Analysis Of Mismatch Repair-Mediated Alkylating Agent-Induced Dna Damage Response, Xi Chen, Yong Zhao, Guo-Min Li, Lin Guo

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: Mediating DNA damage-induced apoptosis is an important genome-maintenance function of the mismatch repair (MMR) system. Defects in MMR not only cause carcinogenesis, but also render cancer cells highly resistant to chemotherapeutics, including alkylating agents. To understand the mechanisms of MMR-mediated apoptosis and MMR-deficiency-caused drug resistance, we analyze a model alkylating agent (N-methyl-N’-nitro-N-nitrosoguanidine, MNNG)-induced changes in protein phosphorylation and abundance in two cell lines, the MMR-proficient TK6 and its derivative MMR-deficient MT1.

RESULTS: Under an experimental condition that MNNG-induced apoptosis was only observed in MutSα-proficient (TK6), but not in MutSα-deficient (MT1) cells, quantitative analysis …

A Content Analysis Of Media Coverage Of The Introduction Of A Smoke-Free Bylaw In Vancouver Parks And Beaches, Arezu Moshrefzadeh, Wendy Rice, Ann Pederson, Chizimuzo T.C. Okoli

Nursing Faculty Publications

The Board of Parks and Recreation in Vancouver, BC approved a smoke-free bylaw in the city's parks, beaches and recreational facilities, effective 1 September 2010. We analyzed local news coverage and portrayal of the bylaw to understand the potential influence of news media on public perception of the bylaw in order to inform the media advocacy work of public health interest groups. We compiled a data set of newspaper articles (n = 90) and conducted a quantitative content analysis to examine content related to the outdoor smoke-free policy, including article slant, topics related to smoking and tobacco control, and any …