Medicine and Health Sciences Commons^™

Eubacterial Spovg Homologs Constitute A New Family Of Site-Specific Dna-Binding Proteins, Brandon L. Jutras, Alicia M. Chenail, Christi L. Rowland, Dustin Carroll, M Clarke Miller, Tomasz Bykowski, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

A site-specific DNA-binding protein was purified from Borrelia burgdorferi cytoplasmic extracts, and determined to be a member of the highly conserved SpoVG family. This is the first time a function has been attributed to any of these ubiquitous bacterial proteins. Further investigations into SpoVG orthologues indicated that the Staphylococcus aureus protein also binds DNA, but interacts preferentially with a distinct nucleic acid sequence. Site-directed mutagenesis and domain swapping between the S. aureus and B. burgdorferi proteins identified that a 6-residue stretch of the SpoVG α-helix contributes to DNA sequence specificity. Two additional, highly conserved amino acid residues on an adjacent …

Diaphragm Weakness In Mechanically Ventilated Critically Ill Patients, Gerald S. Supinski, Leigh Ann Callahan

Internal Medicine Faculty Publications

INTRODUCTION: Studies indicate that mechanically ventilated patients develop significant diaphragm muscle weakness, but the etiology of weakness and its clinical impact remain incompletely understood. We assessed diaphragm strength in mechanically ventilated medical ICU patients, correlated the development of diaphragm weakness with multiple clinical parameters, and examined the relationship between the level of diaphragm weakness and patient outcomes.

METHODS: Transdiaphragmatic twitch pressure (PdiTw) in response to bilateral magnetic stimulation of the phrenic nerves was measured. Diaphragm weakness was correlated with the presence of infection, blood urea nitrogen, albumin, and glucose levels. The relationship of diaphragm strength to patient outcomes, including mortality …

Biomarkers For Ovarian Cancer, Eric T. Fung, Frederick Ueland, J. R. Van Nagell, Paul D. Depriest, Andre T. Baron

Epidemiology and Environmental Health Faculty Patents

The present invention provides protein-based biomarkers and biomarker combinations that are useful in qualifying ovarian cancer status in a patient. In particular, the biomarkers of this invention are useful to classify a subject sample as ovarian cancer, ovarian cancer of low malignant potential, benign ovarian disease or other malignant condition. The biomarkers can be detected by SELDI mass spectrometry.

From The Frontier: Translating Research To Practice…Qi As The Hinge Point, Paul C. Erwin

Frontiers in Public Health Services and Systems Research

This article is number three in the series From the Frontier: Translating Research to Practice. The narrative describes the work of a practice-academic network in Minnesota which explored the degree to which having a culture of quality at the local health department level influenced the capacity to implement a new statewide initiative. The network conducted a mixed-methods study of grantees funded to develop and implement local policy, systems, and environmental change strategies to promote nutrition, increase activity, and reduce tobacco use and exposure. The results of their study indicated that grantees with higher performance levels in Quality Improvement (QI) …

Access To Primary Care: Comparing Driving Distance From Health Professional Shortage Area (Hpsa) Counties Versus Non-Hpsa Counties, Molly Cashion, Stephanie Jilcott-Pitts, Doyle Cummings, Christopher Duffrin, John Jones, Qiang Wu

Frontiers in Public Health Services and Systems Research

The criteria used to identify Health Professional Shortage Areas dates back to the 1970’s and very little has changed since then. This study examined driving distance from patient address to provider address as one component of a geographical HPSA. Primary care-related services located in adjacent areas to whole-county HPSAs are considered excessively distant when travel time exceeds 30 minutes or the equivalent of 20 miles in this study. We found similarities in travel distance to primary care-related services from patients living in HPSA counties compared to those living in non-HPSA counties. This could indicate the need to re-examine HPSA definitions …

Addressing Health Inequalities In The United States: Key Data Trends And Policy Action, Sara N. Bleich, Marian P. Jarlenski, Caryn N. Bell, Thomas A. Laveist

Frontiers in Public Health Services and Systems Research

Health inequalities, which have been well documented for decades, have recently become policy targets in the United States. This report summarizes current patterns and trends in health inequalities, commitments to reduce health inequalities, and progress made to eliminate health inequalities. Time trend data indicate improvements in health status and major risk factors but increases in morbidity, with black and lower-education individuals experiencing a disproportionate burden of disease. A common policy response has been priority setting in the form of national objectives or goals to address health inequalities. More research and better methods are needed to precisely measure relationships between stated …

Protection Of Dietary Polyphenols Against Oral Cancer, Yijian Ding, Hua Yao, Yanan Yao, Leonard Yenwong Fai, Zhuo Zhang

Toxicology and Cancer Biology Faculty Publications

Oral cancer represents a health burden worldwide with approximate 275,000 new cases diagnosed annually. Its poor prognosis is due to local tumor invasion and frequent lymph node metastasis. Better understanding and development of novel treatments and chemo-preventive approaches for the preventive and therapeutic intervention of this type of cancer are necessary. Recent development of dietary polyphenols as cancer preventives and therapeutic agents is of great interest due to their antioxidant and anti-carcinogenic activities. Polyphenols may inhibit carcinogenesis in the stage of initiation, promotion, or progression. In particular, dietary polyphenols decrease incidence of carcinomas and exert protection against oral cancer by …

Nfat5 Represses Canonical Wnt Signaling Via Inhibition Of Β-Catenin Acetylation And Participates In Regulating Intestinal Cell Differentiation, Qingding Wang, Yuning Zhou, Piotr G. Rychahou, Chunming Liu, Heidi L. Weiss, B. Mark Evers

Surgery Faculty Publications

The intestinal mucosa undergoes a continual process of proliferation, differentiation, and apoptosis, which is regulated by multiple signaling pathways. The Wnt/β-catenin pathway has a critical role in this process. Previously, we have shown that the calcineurin-dependent nuclear factor of activated T cell (NFAT) is involved in the regulation of intestinal cell differentiation, as noted by the alteration of brush-border enzyme intestinal alkaline phosphatase (IAP) activity. Here, we show that calcineurin-independent NFAT5 interacts with β-catenin to repress Wnt signaling. We found that overexpression of NFAT5 inhibits, whereas knockdown of NFAT5 increases, TOPflash reporter activity and the expression of …

Influence Of Media Composition On The Growth Rate Of Chlorella Vulgaris And Scenedesmus Acutus Utilized For Co2 Mitigation, Czarena L. Crofcheck, Xinyi E, Aubrey Shea, Michael D. Montross, Mark Crocker, Rodney Andrews

Biosystems and Agricultural Engineering Faculty Publications

Atmospheric carbon dioxide levels have increased since the industrial revolution due to increasing combustion of fossil fuels. One possible CO₂ mitigation strategy is the use of microalgae for mitigation of CO₂. This paper focuses on the influence of media composition on the growth rate of two microalgae strains, Chlorella vulgaris and Scenedesmus actus. A KNO₃ based medium was found to work better for Chlorella, while a urea based equivalent worked better for Scenedesmus. The urea based media investigated here resulted in growth similar to that found with previously reported KNO₃ based media. …

Envelope Determinants Of Equine Lentiviral Vaccine Protection, Jodi K. Craigo, Corin Ezzelarab, Sheila J. Cook, Chong Liu, David W. Horohov, Charles J. Issel, Ronald C. Montelaro

Veterinary Science Faculty Publications

Lentiviral envelope (Env) antigenic variation and associated immune evasion present major obstacles to vaccine development. The concept that Env is a critical determinant for vaccine efficacy is well accepted, however defined correlates of protection associated with Env variation have yet to be determined. We reported an attenuated equine infectious anemia virus (EIAV) vaccine study that directly examined the effect of lentiviral Env sequence variation on vaccine efficacy. The study identified a significant, inverse, linear correlation between vaccine efficacy and increasing divergence of the challenge virus Env gp90 protein compared to the vaccine virus gp90. The report demonstrated approximately 100% protection …

Analyzing Return On Investment In Public Health: Implications And Future Directions, Glen P. Mays

Health Management and Policy Presentations

Return on investment (ROI) analyses of public health programs, policies, and services are being undertaken with increasing frequency to provide assessments of the value of these activities. This presentation reviews current initiatives and future directions for improving the quality of ROI studies and their application to real-world public health policy and administrative decisions.

The Public Health Pbrn Program: Building The Science Of Public Health Delivery, Glen P. Mays, Anna Goodman Hoover

Health Management and Policy Presentations

This session describes public health practice-based research networks (PBRNs) and emerging opportunities for collaboration with injury control research centers to advance the science of injury prevention practice.

Dynamic Functions Of Rhoa In Tumor Cell Migration And Invasion, Kathleen L. O'Connor, Min Chen

Markey Cancer Center Faculty Publications

RhoA is one of the more extensively studied members of the Rho family of small GTPase where it is most readily recognized for its contributions to actin-myosin contractility and stress fiber formation. Accordingly, RhoA function during cell migration has been relegated to the rear of the cell where it mediates retraction of the trailing edge. However, RhoA can also mediate membrane ruffling, lamellae formation and membrane blebbing, thus suggesting an active role in membrane protrusions at the leading edge. With the advent of fluorescence resonance energy transfer (FRET)-based Rho activity reporters, RhoA has been shown to be active at the …

Relationship Between Serum And Brain Carotenoids, Α-Tocopherol, And Retinol Concentrations And Cognitive Performance In The Oldest Old From The Georgia Centenarian Study, Elizabeth J. Johnson, Rohini Vishwanathan, Mary Ann Johnson, Dorothy B. Hausman, Adam Davey, Tammy M. Scott, Robert C. Green, L. Stephen Miller, Marla Gearing, John Woodard, Peter T. Nelson, Hae-Yun Chung, Wolfgang Schalch, Jonas Wittwer, Leonard W. Poon

Sanders-Brown Center on Aging Faculty Publications

Oxidative stress is involved in age-related cognitive decline. The dietary antioxidants, carotenoids, tocopherols, and vitamin A may play a role in the prevention or delay in cognitive decline. In this study, sera were obtained from 78 octogenarians and 220 centenarians from the Georgia Centenarian Study. Brain tissues were obtained from 47 centenarian decedents. Samples were analyzed for carotenoids, α-tocopherol, and retinol using HPLC. Analyte concentrations were compared with cognitive tests designed to evaluate global cognition, dementia, depression and cognitive domains (memory, processing speed, attention, and executive functioning). Serum lutein, zeaxanthin, and β-carotene concentrations were most consistently related to better cognition …

Harnessing The Power Of Public Health Systems For Injury Prevention & Control, Glen P. Mays

Health Management and Policy Presentations

Efforts to improve population health hinge on a vast yet diffuse constellation of government agencies, health care providers, and community organizations that assume responsibilities in implementing prevention programs and policies across the U.S. Realizing the full health and economic benefits of injury prevention and control initiatives requires mobilizing and managing these complex and heterogeneous public health delivery systems. This session will explore the emerging science of public health delivery systems and what it tells us about improving injury prevention and control amid policy and economic change.

Public Health Delivery Systems And Population Health, Glen P. Mays

Health Management and Policy Presentations

Despite high overall health expenditures, the U.S. continues to fall behind other high-income countries on many measures of population health. While health care delivery systems are now studied intensively for solutions to U.S. cost and quality problems, the nation's delivery systems for public health programs and policies are only now becoming the subject of rigorous empirical study. This presentation examines recent studies of public health delivery systems and important directions for future inquiry.

Intracranial Injection Of Gammagard, A Human Ivig, Modulates The Inflammatory Response Of The Brain And Lowers AΒ In App/Ps1 Mice Along A Different Time Course Than Anti-AΒ Antibodies, Tiffany L. Sudduth, Abigail Greenstein, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

Gammagard IVIg is a therapeutic approach to treat Alzheimer's disease currently in phase 3 clinical trials. Despite the reported efficacy of the approach the mechanism of action is poorly understood. We have previously shown that intracranial injection of anti-Aβ antibodies into the frontal cortex and hippocampus reveals important information regarding the time course of events once the agent is in the brain. In the current study we compared IVIg, mouse-pooled IgG, and the anti-Aβ antibody 6E10 injected intracranially into the frontal cortex and hippocampus of 7-month-old APP/PS1 mice. We established a time course of events ranging from 1 …

Green Tea Polyphenols And Sulfasalazine Have Parallel Anti-Inflammatory Properties In Colitis Models, Helieh S. Oz, Theresa Chen, Willem J.S. De Villiers

Internal Medicine Faculty Publications

Background: There is no cure for autoimmune chronic inflammatory bowel disease (IBD). IBD patients commonly use complementary and alternative medications of which the safety, efficacy, and interaction with standard-of-care therapies are not fully known. Thus the consequences can become life-threatening. Sulfasalazine commonly used in IBD, potentially has severe adverse effects, including infertility, pulmonary fibrosis, lack of response, and ultimately patients may require intestinal resection. We hypothesized that green tea polyphenols (GrTP, EGCG) and sulfasalazine have similar anti-inflammatory properties.

Methods: BALB/c mice received Dextran sodium sulfate (DSS) to induce colitis (ulcerative colitis model). Exposure of IL-10 deficient mice (BALB/c-background) to normal …

Tobacco Treatment Outcomes From A Specialist Smoking Cessation Clinic Based Within Cardiology Services, Milan Khara, Chizimuzo T.C. Okoli

Nursing Presentations

BACKGROUND: Populations with cardiac conditions often continue to smoke at high rates (up to 62%), even after experiencing life-threatening cardiac events. The purpose of our study is to examine pilot treatment outcomes of an outpatient Smoking Cessation Clinic (SCC) provided within Cardiology Services.

METHODS: This study is based on a retrospective review of the charts of 118 participants of the SCC (between Sept 2010 and May 2012). The primary components of intervention include tailored pharmacotherapy and behavioural counselling. The main outcome of interest is self-reported 7-day point-prevalence of smoking abstinence verified by expired CO level (when available).

RESULTS: 34.7% …

Block Copolymer Self-Assembled And Cross-Linked Nanoassemblies For Combination Delivery Of Iron Oxide And Doxorubicin, Daniel Scott, Yihwa Beabout, Robert J. Wydra, Mo Dan, Robert A. Yokel, J. Zach Hilt, Younsoo Bae

Pharmaceutical Sciences Faculty Publications

We describe the development of nanoscale polymer drug carriers for the combinational delivery of an anticancer drug (doxorubicin: DOX) along with super paramagnetic iron oxide nanoparticles (IONPs). The drug molecules were electrostatically loaded into both block copolymer self-assembled nanoassemblies (SNAs) and cross-linked nanoassemblies (CNAs). Both nanoassemblies entrapped DOX and IONPs either individually or in tandem, maintaining sub-100 nm diameter. The IONP-loaded nanoassemblies generated heat in the presence of an alternating magnetic field (AMF). Incorporation of the drug payload, DOX, showed no adverse effects on the heating profile. Drug release from the SNAs and CNAs was accelerated as temperature increased from …

Reliability Of The Myotonometer For Assessment Of Posterior Shoulder Tightness, Caitlyn M. Kerins, Stephanie D. Moore, Timothy A. Butterfield, Patrick O. Mckeon, Timothy L. Uhl

Physical Therapy Faculty Publications

BACKGROUND/PURPOSE: The Myotonometer® is an electronic tissue compliance meter that has been used to quantify the compliance of soft tissues. The Myotonometer® may be a valuable tool to measure the effectiveness of interventions commonly used to increase tissue compliance in individuals with posterior shoulder tightness (PST). Limited data exist on reliability and responsiveness of the Myotonometer® for assessment of soft tissues about the shoulder; therefore, the purpose of this study is to determine the intra- and inter-session reliability and responsiveness of the Myotonometer® in measuring tissue compliance of the posterior shoulder musculature in asymptomatic subjects with PST.

METHODS: Fifteen asymptomatic …

Uv Radiation And The Skin, John A. D'Orazio, Stuart G. Jarrett, Alexandra Amaro-Ortiz, Timothy Scott

Toxicology and Cancer Biology Faculty Publications

UV radiation (UV) is classified as a "complete carcinogen" because it is both a mutagen and a non-specific damaging agent and has properties of both a tumor initiator and a tumor promoter. In environmental abundance, UV is the most important modifiable risk factor for skin cancer and many other environmentally-influenced skin disorders. However, UV also benefits human health by mediating natural synthesis of vitamin D and endorphins in the skin, therefore UV has complex and mixed effects on human health. Nonetheless, excessive exposure to UV carries profound health risks, including atrophy, pigmentary changes, wrinkling and malignancy. UV is epidemiologically and …

Bioactive Lipids And Cationic Antimicrobial Peptides As New Potential Regulators For Trafficking Of Bone Marrow-Derived Stem Cells In Patients With Acute Myocardial Infarction, Anush V. Karapetyan, Yuri M. Klyachkin, Samy Selim, Manjula Sunkara, Khaled M. Ziada, Donald A. Cohen, Ewa K. Zuba-Surma, Janina Ratajczak, Susan S. Smyth, Mariusz Z. Ratajczak, Andrew J. Morris, Ahmed Abdel-Latif

Internal Medicine Faculty Publications

Acute myocardial infarction (AMI) triggers mobilization of stem cells from bone marrow (BM) into peripheral blood (PB). Based on our observation that the bioactive sphingophospholipids, sphingosine-1 phosphate (S1P), and ceramide-1 phosphate (C1P) regulate trafficking of hematopoietic stem cells (HSCs), we explored whether they also direct trafficking of non-hematopoietic stem cells (non-HSCs). We detected a 3–6-fold increase in circulating CD34+, CD133+, and CXCR4+ lineage-negative (Lin−)/CD45− cells that are enriched in non-HSCs [including endothelial progenitors (EPCs) and very small embryonic-like stem cells (VSELs)] in PB from AMI patients (P<0.05 vs. controls). Concurrently, we measured a 3-fold increase in S1P and C1P levels in plasma from AMI patients. At the same time, plasma obtained at hospital admission and 6 h after AMI strongly chemoattracted human BM-derived CD34+/Lin− and CXCR4+/Lin− cells in Transwell chemotaxis assays. This effect of plasma was blunted after depletion of S1P level by charcoal stripping and was further inhibited by the specific S1P1 receptor antagonist such as W146 and VPC23019. We also noted that the expression of S1P receptor 1 (S1P1), which is dominant in naïve BM, is reduced after the exposure to S1P at concentrations similar to the plasma S1P levels in patients with AMI, thus influencing the role of S1P in homing to the injured myocardium. Therefore, we examined mechanisms, other than bioactive lipids, that may contribute to the homing of BM non-HSCs to the infarcted myocardium. Hypoxic cardiac tissue increases the expression of cathelicidin and β-2 defensin, which could explain why PB cells isolated from patients with AMI migrated more efficiently to a low, yet physiological, gradient of stromal-derived factor-1 in Transwell migration assays. Together, these observations suggest that while elevated S1P and C1P levels early in the course of AMI may trigger mobilization of non-HSCs into PB, cathelicidin and β-2 defensin could play an important role in their homing to damaged myocardium.

Estimating Return On Investment: Approaches And Methods, Glen P. Mays

Health Management and Policy Presentations

Continuing fiscal constraints in the public sector and large-scale policy changes associated with health reform implementation in the U.S. are giving heightened attention to questions about the health and economic value of public health programs, services, and policies -- strategies designed to protect health and prevent disease and injury on a population-wide basis. This session provides an overview of approaches for conducting return-on-investment (ROI) analyses and related economic evaluation studies in public health settings in order to inform policy and administrative decision-making. New opportunities and resources created through CDC's National Public Health Improvement Initiative (NPHII) and RWJF's Public Health Practice-based …

Amyloid-Β Probes: Review Of Structure-Activity And Brain-Kinetics Relationships, Todd J. Eckroat, Abdelrahman S. Mayhoub, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

The number of people suffering from Alzheimer's disease (AD) is expected to increase dramatically in the coming years, placing a huge burden on society. Current treatments for AD leave much to be desired, and numerous research efforts around the globe are focused on developing improved therapeutics. In addition, current diagnostic tools for AD rely largely on subjective cognitive assessment rather than on identification of pathophysiological changes associated with disease onset and progression. These facts have led to numerous efforts to develop chemical probes to detect pathophysiological hallmarks of AD, such as amyloid-β plaques, for diagnosis and monitoring of therapeutic efficacy. …

Optimizing The Value Of Public Health Services: Lessons From Research & Practice, Glen P. Mays

Health Management and Policy Presentations

Expanding the delivery of efficacious public health programs and policies holds considerable potential for improving population health and constraining the growth in health care spending. Achieving such expansions efficiently, particularly in low-resource settings, requires careful attention to interorganizational and intergovernmental relationships in public health delivery.

Comprehensive Behavioral Characterization Of An App/Ps-1 Double Knock-In Mouse Model Of Alzheimer's Disease, Scott J. Webster, Adam D. Bachstetter, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: Despite the extensive mechanistic and pathological characterization of the amyloid precursor protein (APP)/presenilin-1 (PS-1) knock-in mouse model of Alzheimer's disease (AD), very little is known about the AD-relevant behavioral deficits in this model. Characterization of the baseline behavioral performance in a variety of functional tasks and identification of the temporal onset of behavioral impairments are important to provide a foundation for future preclinical testing of AD therapeutics. Here we perform a comprehensive behavioral characterization of this model, discuss how the observed behavior correlates with the mechanistic and pathological observations of others, and compare this model with other commonly used …

Significant Sequelae After Bacterial Meningitis In Niger: A Cohort Study, Jean-François Jusot, Zilahatou Tohon, Abdoul Aziz Yazi, Jean-Marc Collard

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: Beside high mortality, acute bacterial meningitis may lead to a high frequency of neuropsychological sequelae. The Sahelian countries belonging to the meningitis belt experience approximately 50% of the meningitis cases occurring in the world. Studies in Africa have shown that N. meningitidis could cause hearing loss in up to 30% of the cases, exceeding sometimes measles. The situation is similar in Niger which experiences yearly meningitis epidemics and where rehabilitation wards are rare and hearing aids remain unaffordable. The aim of this study was to estimate the frequency of neuropsychological sequelae after acute bacterial meningitis in four of the …

National Estimates Of Emergency Department Visits For Pediatric Severe Sepsis In The United States, Sara Singhal, Mathias W. Allen, John-Ryan Mcannally, Kenneth S. Smith, John P. Donnelly, Henry E. Wang

Emergency Medicine Faculty Publications

Objective. We sought to determine the characteristics of children presenting to United States (US) Emergency Departments (ED) with severe sepsis.

Study design. Cross-sectional analysis using data from the National Hospital Ambulatory Medical Care Survey (NHAMCS). Using triage vital signs and ED diagnoses (defined by the International Classification of Diseases, Ninth Revision codes), we identified children(triage fever or ICD-9 infection) and organ dysfunction (triage hypotension or ICD-9 organ dysfunction).

Results. Of 28.2 million pediatric patients presenting to US EDs each year, severe sepsis was present in 95,055 (0.34%; 95% CI: 0.29-0.39%). Fever and respiratory infection were the most common indicators of …

Truck Driver Dies When Tractor-Trailer Overturns After Leaving Road, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Motor Vehicle

In the early morning hours of a spring day around 5:45 a.m., a 55-year-old male truck driver was driving south on an interstate transporting sheet metal. It is unknown how long he had been driving when he exited from the highway, traveled partially up the ramp, and struck the left side guard rail. The truck left the road, traveled down an embankment and overturned onto its roof. A passing motorist called emergency medical services. The driver was extricated by mechanical means and declared dead at the scene.

To prevent future occurrences of similar incidents, the following recommendations have been made: …