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National Health Security Preparedness Index Joint Workgroup Meeting On Model Design And Analytic Methodology, Glen P. Mays

Health Management and Policy Presentations

This workgroup meeting of the National Health Security Preparedness Index reviews results from the 2016 release of the Index and examines opportunities for enhancing the Index measures and analytic methodologies for subsequent releases.

Transcriptome Analysis Of B Cell Immune Functions In Periodontitis: Mucosal Tissue Responses To The Oral Microbiome In Aging, Jeffrey L. Ebersole, Sreenatha S. Kirakodu, Michael John Novak, Luis Orraca, Janis Gonzalez-Martinez, Larry Cunningham Jr., Mark V. Thomas, Arnold J. Stromberg, Subramanya N. Pandruvada, Octavio A. Gonzalez

Center for Oral Health Research Faculty Publications

Evidence has shown activation of T and B cells in gingival tissues in experimental models and in humans diagnosed with periodontitis. The results of this adaptive immune response are noted both locally and systemically with antigenic specificity for an array of oral bacteria, including periodontopathic species, e.g., Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. It has been recognized through epidemiological studies and clinical observations that the prevalence of periodontitis increases with age. This report describes our studies evaluating gingival tissue transcriptomes in humans and specifically exploiting the use of a non-human primate model of naturally occurring periodontitis to delineate gingival mucosal …

A Randomized, Double-Blind, Placebo-Controlled Phase Ii Trial Investigating The Safety And Immunogenicity Of Modified Vaccinia Ankara Smallpox Vaccine (Mva-Bn®) In 56-80-Year-Old Subjects, Richard N. Greenberg, Christine M. Hay, Jack T. Stapleton, Thomas C. Marbury, Eva Wagner, Eva Kreitmeir, Siegfried Röesch, Alfred Von Krempelhuber, Philip Young, Richard Nichols, Thomas P. Meyer, Darja Schmidt, Josef Weigl, Garth Virgin, Nathaly Arndtz-Wiedemann, Paul Chaplin

Internal Medicine Faculty Publications

Background Modified Vaccinia Ankara MVA-BN^® is a live, highly attenuated, viral vaccine under advanced development as a non-replicating smallpox vaccine. In this Phase II trial, the safety and immunogenicity of Modified Vaccinia Ankara MVA-BN^® (MVA) was assessed in a 56–80 years old population.

Methods MVA with a virus titer of 1 x 10⁸ TCID₅₀/dose was administered via subcutaneous injection to 56–80 year old vaccinia-experienced subjects (N = 120). Subjects received either two injections of MVA (MM group) or one injection of Placebo and one injection of MVA (PM group) four weeks apart. Safety was evaluated …

Data Correlations Between Gender, Cytomegalovirus Infection And T Cells, Nk Cells, And Soluble Immune Mediators In Elderly Humans, Ahmad Al-Attar, Steven R. Presnell, Charlotte A. Peterson, D. Travis Thomas, Charles T. Lutz

Pathology and Laboratory Medicine Faculty Publications

We describe a cohort of 50 elderly subjects, age at least 70 years. We present gender-specific findings in T lymphocyte markers and soluble immune mediators. We show the correlation between cytomegalovirus infection status with CD56^dim NK cell responses to a variety of stimuli and with CD56^bright/CD56^dim NK cell ratio. We also present the correlation of retinol binding protein (RBP)−4 plasma levels with NK cell responses and we explore the relationship between gender and adiponectin, 25(OH)D (vitamin D), and RBP4 in affecting CD56^dim NK cell responses. These data are discussed in Al-Attar et al. (2016)

Identification Of Ecdysone Hormone Receptor Agonists As A Therapeutic Approach For Treating Filarial Infections, Amruta S. Mhashilkar, Sai L. Vankayala, Canhui Liu, Fiona Kearns, Priyanka Mehrotra, George Tzertzinis, Subba R. Palli, H. Lee Woodcock, Thomas R. Unnasch

Entomology Faculty Publications

Background A homologue of the ecdysone receptor has previously been identified in human filarial parasites. As the ecdysone receptor is not found in vertebrates, it and the regulatory pathways it controls represent attractive potential chemotherapeutic targets.

Methodology/ Principal Findings Administration of 20-hydroxyecdysone to gerbils infected with B. malayi infective larvae disrupted their development to adult stage parasites. A stable mammalian cell line was created incorporating the B. malayi ecdysone receptor ligand-binding domain, its heterodimer partner and a secreted luciferase reporter in HEK293 cells. This was employed to screen a series of ecdysone agonist, identifying seven agonists active at …

Genetic Engineering And Sustainable Crop Disease Management: Opportunities For Case-By-Case Decision-Making, Paul Vincelli

Plant Pathology Faculty Publications

Genetic engineering (GE) offers an expanding array of strategies for enhancing disease resistance of crop plants in sustainable ways, including the potential for reduced pesticide usage. Certain GE applications involve transgenesis, in some cases creating a metabolic pathway novel to the GE crop. In other cases, only cisgenessis is employed. In yet other cases, engineered genetic changes can be so minimal as to be indistinguishable from natural mutations. Thus, GE crops vary substantially and should be evaluated for risks, benefits, and social considerations on a case-by-case basis. Deployment of GE traits should be with an eye towards long-term sustainability; several …

Learning From Geographic Variation And Change In Preparedness: The 2016 National Health Security Preparedness Index, Glen P. Mays

Health Management and Policy Presentations

The 2016 release of the National Health Security Preparedness Index tracks the nation's progress in preparing for disasters and other emergencies that create health risks for large groups of people. Recent improvements in the Index computational methodologies and measures allow results to be compared validly across states and over time. The Index aggregates more than 130 individual measures from nearly 60 data sources into valid composite measures for 6 domains and 19 subdomains that reflect core functional areas of emergency preparedness and response. Improvements in normalization, weighting, imputation, and confidence interval construction enhance the validity and reliability of Index estimates …

African American Female Offender's Use Of Alternative And Traditional Health Services After Re-Entry: Examining The Behavioral Model For Vulnerable Populations, Carrie B. Oser, Amanda M. Bunting, Erin L. Pullen, Danelle Stevens-Watkins

Sociology Faculty Publications

This is the first known study to use the Gelberg-Andersen Behavioral Model for Vulnerable Populations to predict African American women's use of three types of health services (alternative, hospitalization, and ambulatory) in the 18 months after release from prison. In the multivariate models, the most robust predictors of all three types of service utilization were in the vulnerable theoretical domains. Alternative health services were predicted by ethnic community membership, higher religiosity, and HIV/HCV. Hospitalizations were predicted by the lack of barriers to health care and disability. Ambulatory office visits were predicted by more experiences of gendered racism, a greater number …

Summary Of Results From The 2016 National Health Security Preparedness Index, Glen P. Mays, Michael T. Childress, Pierre Martin Dominique Zephyr, Anna Goodman Hoover

Health Management and Policy Reports

The National Health Security Preparedness Index tracks the nation’s progress in preparing for, responding to, and recovering from disasters and other large-scale emergencies that pose risks to health and well-being in the United States. Because health security is a responsibility shared by many different stakeholders in government and society, the Index combines measures from multiple sources and perspectives to offer a broad view of the health protections in place for nation as a whole and for each U.S. state. The Index identifies strengths as well as gaps in the protections needed to keep people safe and healthy in the face …

Respiratory Muscle Paralysis Associated With Colistin, Polymyxin B, And Muscle Relaxants Drugs: A Case Report, Thein Myint, Martin E. Evans, Donna R. Burgess, Richard N. Greenberg

Internal Medicine Faculty Publications

Polymyxins B and E (colistin) exert a bactericidal effect on the gram-negative bacterial cell wall, causing permeability changes in the cytoplasmic membrane, leading to cell death. Their use was substantially decreased in clinical practice from the 1970s to 2000s due to their significant nephrotoxicity and neurotoxicity compared to the newly introduced antibiotics. The increasing prevalence of multidrug-resistant gram-negative bacteria infections in this century has led to an upsurge in the use of these “older” drugs. Respiratory paralysis caused by neuromuscular blockage associated with the use of polymyxin B and E was reported mostly in literature published in the 1960s to …

Decrease In Driveline Infections With Change In Driveline Management Protocol, Saima Aslam, Jennifer Dan, Amanda Topik, Michael Belyk, Francesca Torriani, Randy Taplitz, Jorge Silva-Enciso, Denise Barnard, Barry Greenberg, Jack Copeland, Victor Pretorius, Eric Adler

The VAD Journal

Background: Driveline infections (DLI) are a significant cause of morbidity and mortality in ventricular assist device (VAD) recipients. We compared driveline infection (DLI) rate after an institutional change in driveline management protocol.

Methods: We retrospectively reviewed records of left VAD recipients at our institution, based on driveline management. Group 1: daily driveline dressing change consisting of chlorhexidine cleansing, sterile 4x4 gauze, and use of an abdominal binder. Group 2: Dressing change every 3 days consisting of chlorhexidine cleansing, non-sterile silver-impregnated foam with overlying clear dressing, and use of a driveline anchor. Follow-up was censored at first DLI, device removal, transplant …

Structures Of Eccb1 And Eccd1 From The Core Complex Of The Mycobacterial Esx-1 Type Vii Secretion System, Jonathan Mark Wagner, Sum Chan, Timothy J. Evans, Sara Kahng, Jennifer Kim, Mark A. Arbing, David Eisenberg, Konstantin V. Korotkov

Molecular and Cellular Biochemistry Faculty Publications

Background: The ESX-1 type VII secretion system is an important determinant of virulence in pathogenic mycobacteria, including Mycobacterium tuberculosis. This complicated molecular machine secretes folded proteins through the mycobacterial cell envelope to subvert the host immune response. Despite its important role in disease very little is known about the molecular architecture of the ESX-1 secretion system.

Results: This study characterizes the structures of the soluble domains of two conserved core ESX-1 components – EccB₁ and EccD₁. The periplasmic domain of EccB₁ consists of 4 repeat domains and a central domain, which together form a quasi …

Targeting An Essential Gtpase Obg For The Development Of Broad-Spectrum Antibiotics, Josephine A. Bonventre, Ryszard A. Zielke, Konstantin V. Korotkov, Aleksandra E. Sikora

Molecular and Cellular Biochemistry Faculty Publications

A promising new drug target for the development of novel broad-spectrum antibiotics is the highly conserved small GTPase Obg (YhbZ, CgtA), a protein essential for the survival of all bacteria including Neisseria gonorrhoeae (GC). GC is the agent of gonorrhea, a prevalent sexually transmitted disease resulting in serious consequences on reproductive and neonatal health. A preventive anti-gonorrhea vaccine does not exist, and options for effective antibiotic treatments are increasingly limited. To address the dire need for alternative antimicrobial strategies, we have designed and optimized a 384-well GTPase assay to identify inhibitors of Obg using as a model Obg protein from …

The Significance Of A Common Idiotype (1f7) On Antibodies Against Human Immune Deficiency Virus Type 1 And Hepatitis C Virus, Sybille Muller, Matthew S. Parsons, Heinz Kohler, Michael Grant

Microbiology, Immunology, and Molecular Genetics Faculty Publications

In this review, we trace the concept and potential functional role of regulatory idiotypes in the immune response to human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus, and hepatitis C virus (HCV). A major idiotype involved in these viral infections is recognized and defined by a murine monoclonal antibody (1F7). Antibodies expressing the idiotype defined by 1F7 are dominant in HIV-1 infection and are also found on many broadly neutralizing antibodies against HIV-1. This regulatory idiotypic axis offers opportunities for exploitation in vaccine development for HIV-1, HCV, and other chronic viral infections.

Unique Features Of A Global Human Ectoparasite Identified Through Sequencing Of The Bed Bug Genome, Joshua B. Benoit, Zach N. Adelman, Klaus Reinhardt, Amanda Dolan, Monica Poelchau, Emily C. Jennings, Elise M. Szuter, Richard W. Hagan, Hemant Gujar, Jayendra Nath Shukla, Fang Zhu, M. Mohan, David R. Nelson, Andrew J. Rosendale, Christian Derst, Valentina Resnik, Sebastian Wernig, Pamela Menegazzi, Christian Wegener, Nicolai Peschel, Jacob M. Hendershot, Wolfgang Blenau, Reinhard Predel, Paul R. Johnston, Panagiotis Ioannidis, Robert M. Waterhouse, Ralf Nauen, Corinna Schorn, Mark-Christoph Ott, Frank Maiwald, Subba R. Palli

Entomology Faculty Publications

The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host-symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome …

Gene Deletion By Fluorescence-Reported Allelic Exchange Mutagenesis In Chlamydia Trachomatis, Konrad E. Mueller, Katerina Wolf, Kenneth A. Fields

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Although progress in Chlamydia genetics has been rapid, genomic modification has previously been limited to point mutations and group II intron insertions which truncate protein products. The bacterium has thus far been intractable to gene deletion or more-complex genomic integrations such as allelic exchange. Herein, we present a novel suicide vector dependent on inducible expression of a chlamydial gene that renders Chlamydia trachomatis fully genetically tractable and permits rapid reverse genetics by fluorescence-reported allelic exchange mutagenesis (FRAEM). We describe the first available system of targeting chlamydial genes for deletion or allelic exchange as well as curing plasmids from C. trachomatis …

Vaccines And The Looming Threat Of Syphilis, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

During the past several decades, syphilis has increased in the US and explosively so in China and Russia.While most current cases can be cured by penicillin or second line antibiotics, strains of the syphilis spirochete (Treponema pallidum) resistant to the latter have emerged.And the potential of strains to acquire resistance to penicillin via plasmids has recently been recognized.The 36 million-plus undertreated cases of syphilis in the world represent metaphorically a vast global 37°C incubator allowing exchange of antibiotic resistant genes among the human-borne bacteria and theoretically permitting the emergence of penicillin resistant strains.None has yet been identified but …

Local Admixture Of Amplified And Diversified Secreted Pathogenesis Determinants Shapes Mosaic Toxoplasma Gondii Genomes, Hernan Lorenzi, Asis Khan, Michael S. Behnke, Sivaranjani Namasivayam, Lakshmipuram S. Swapna, Michalis Hadjithomas, Svetlana Karamycheva, Deborah Pinney, Brian P. Brunk, James W. Ajioka, Daniel Ajzenberg, John C. Boothroyd, Jon P. Boyle, Marie L. Dardé, Maria A. Diaz-Miranda, Jitender P. Dubey, Heather M. Fritz, Solange M. Gennari, Brian D. Gregory, Kami Kim, Jeroen P. J. Saeij, Chunlei Su, Michael W. White, Xing-Quan Zhu, Daniel K. Howe, Benjamin M. Rosenthal, Michael E. Grigg, John Parkinson, Liang Liu, Jessica C. Kissinger

Veterinary Science Faculty Publications

Toxoplasma gondii is among the most prevalent parasites worldwide, infecting many wild and domestic animals and causing zoonotic infections in humans. T. gondii differs substantially in its broad distribution from closely related parasites that typically have narrow, specialized host ranges. To elucidate the genetic basis for these differences, we compared the genomes of 62 globally distributed T. gondii isolates to several closely related coccidian parasites. Our findings reveal that tandem amplification and diversification of secretory pathogenesis determinants is the primary feature that distinguishes the closely related genomes of these biologically diverse parasites. We further show that the unusual population structure …

Evaluation Of Guideline-Recommended Combined Antiretroviral Treatment Regimens In Commercially-Insured Patients Living In The United States Between 2007 And 2009, Joye Brigitte Allen

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Background: Randomized clinical trials of combination antiretroviral therapy (cART) inform the use of specific antiretrovirals (ARV) and their combination for optimizing therapeutic efficacy. It is critical that patients have access to and receive the most appropriate first-line treatment.

Objective: To examine factors that impact receiving initial guideline-recommended cART within a cohort of commercially insured patients in the United States (US)

Research Design: A population based cohort study.

Data Sources: A secondary administrative insurance claims database.

Subjects: Employed, commercially insured individuals with HIV who were continuously eligible for insurance coverage from January 2007 through December 2009 and received a new ARV …

Undiagnosed Pulmonary Obstruction And Restriction And Dust Exposure: Pilot Investigations Examining The Relationship Among Agricultural Workers, Caroline E. Holsinger

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Chronic obstructive pulmonary disease (COPD) is a progressive disease that is characterized by limited airflow.1 In the United States (U.S.) alone, COPD is the third leading cause of death.2,3 While smoking remains the strongest risk factor for COPD, 20 percent of patients who die from COPD have never smoked.5–7 The American Thoracic 3 Society showed that about 15% of COPD cases might be attributable to workplace exposure.8 Agricultural dust exposure has long been recognized as a cause of decreased respiratory function, and exposures to both forms of dust may exacerbate other important risk factors of COPD and lead to the …

The Association Between Latent Tuberculosis Infection And Diabetes Mellitus Control In The United States, Whitney L. Remy

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Rationale: Diabetes mellitus (DM) is recognized as a common comorbid condition for tuberculosis (TB). Those with comorbid conditions are more likely to develop active TB, to have trouble with treatment, and to have more severe symptoms.

Objective: To measure the prevalence and distribution of latent tuberculosis infection (LTBI) and DM control in the United State and test their association when measured by tuberculin skin test (TST) or QuantiFERON®-TB Gold In-Tube blood test (QFT-GIT) and by HbA1c, respectively. Literature Review: One-third of the world population is infected with TB. Ten percent of TB cases worldwide are linked to diabetes mellitus. Studies …

The Influence Of Time On Food Intake Patterns: Age, Period, Cohort Differences, Karina L. Christopher

Theses and Dissertations--Gerontology

The impact of diet and exercise on overall health and chronic disease risk has been well examined. Multiple studies show that Americans eat more now than they did fifty years ago. What isn’t known is how much of an impact time has on food intake patterns of individuals in terms of different age groups, historic periods of structural influences, and birth cohorts.

In order to identify the impact of time on food intake this study examined time from multiple perspectives. The first aim of this study was to determine food intake patterns among age groups across five time periods using …

Protecting Kentucky's Honey Bees: What's Killing The Buzz, Why It Matters, And What We Can Do To Help, Christine M. Ficker

Kentucky Journal of Equine, Agriculture, & Natural Resources Law

No abstract provided.

The Impact Of An Ambulatory Clinical Intervention On Viral Load Suppression And Retention In Care For Newly Diagnosed Hiv Persons, Latasha R. Jones

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Ambulatory clinical healthcare settings that serve patients infected with the human immunodeficiency virus (HIV) are critical in improving access to quality HIV care and treatment, in part due to their ability to streamline patient care along the HIV care continuum. Barriers to HIV care are significant among newly diagnosed HIV patients and in order to engage and retain these individuals in care and treatment, specific interventions must be in place to link these individuals to care. In this study, the difference in differences method was used for data analysis to measure the impact of an ambulatory clinics intervention on their …

The Role Of Capillaries In The Lesser Ailments Of Old Age And In Alzheimer's Disease And Vascular Dementia: The Potential Of Pro-Therapeutic Angiogenesis, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Apart from chronic diseases (arthritis, diabetes, etc.), old age is generally characterized by three lesser ailments: muscle weakness, minor memory lapses, and cold intolerance. This trio of complaints may have a common, underlying cause, namely, the age-associated reduced microcirculation in muscles, brain, skin, and elsewhere in the body. The Angiogenesis Hypothesis proposes that old age is in part a deficiency disease due to the decline in angiogenic (AG) factors, resulting in a reduced capillary density (CD) throughout the body. Over fifty published papers document waning levels of AG factors and/or decreased CD in various organ systems of aged animals and …

Comparison Of The Difference In Nephrotoxicity Between Nafcillin And Piperacillin-Tazobactam, Sonali Kishor Patel

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Objective

To evaluate whether nephrotoxicity differs between nafcillin and piperacillin-tazobactam in adult hospitalized patients.

Introduction

Acute kidney injury (AKI) is a significant cause of morbidity and mortality in the inpatient setting, with antibiotics being a significant contributor. There is evidence of an increased risk of nephrotoxicity with the combination of vancomycin and piperacillin-tazobactam compared to vancomycin and cefepime or vancomycin alone. It is unknown whether this effect is exclusive for piperacillin-tazobactam. Therefore, in order to promote optimal medication therapy for inpatient bacterial infections, there is a need to assess the persistence of this difference in other beta-lactam antibiotics.

Methods

A …

Correlates Of Antibiotic Diversion In The Philippines: Misconceptions And Community-Level Access To Nonmedical Sources Of Antibiotics, Daniel Alexander Barber

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Aim: To identify sociodemographic, knowledge, and attitudinal correlates to antibiotic diversion among a community-based sample of adults (age 18 and older) in a low-income setting of the Philippines and to explore community-level data on informal antibiotic distribution in sari-sari stands.

Methods: Participants (n=307) completed self-administered surveys. Correlates to antibiotic diversion were assessed using logistic regression with Firth’s bias-adjusted estimates. Availability and characteristics of antibiotics in the sari-sari stands (n=106) were observed through site visits.

Results: A majority (78%) had shared antibiotics in their lifetime, most often with family members. In multivariable analysis, agreement with the belief that it is safe …

Correlates Of Hepatitis C Serostatus Disclosure In Rural Appalachian Kentucky, Megan G. Hofmeister

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Aim: To identify demographic, behavioral, and interpersonal characteristics associated with hepatitis C (HCV) serostatus disclosure among adult, rural, high-risk people who use drugs (PWUD) in Appalachian Kentucky.

Methods: Laboratory confirmed HCV antibody-positive participants (n=243), drawn from the fifth follow-up assessment of a longitudinal study of rural PWUD, completed interviewer-administered questionnaires eliciting demographic and interpersonal characteristics, risk behaviors, and information on HCV disclosure. Correlates of HCV disclosure were assessed using logistic regression.

Results: Most (69.1%) reported disclosing their HCV-positive status to at least one of their social referents (current or past sex partners, current or past injection drug use (IDU) partners, …

Birth Cohort Effects In Risk Factors For Alzheimer’S Disease, Kingsley Uzodinma

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Background and Objectives: The purpose of this study was to assess the presence of birth cohort effects by exploring differences in established risk factors of Alzheimer’s disease (AD) and dementia using case-control designs and also estimate the AD risk among women with respect to their number of biological children.

Methods: This is a case control study design of participants born in 1896 – 1955 and were enrolled in one of the designated Alzheimer’s disease centers (ADCs). The uniform Data Set of the National Alzheimer’s Coordinating center (NACC) include those who had Alzheimer’s disease or mild cognitive impairment (cases) and were …

"Life Skills Training" Prescription Drug Abuse Prevention Among Youth In Bell County, Kentucky, Arveen Kaur

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Prescription Drug Abuse (PDA) has become a serious public health concern and a major epidemic in the United States (U.S.). According to the 2014 National Survey on Drug Use and Health (NSUDH), approximately 15 million people (aged 12 or older) used prescription drugs in the past year and 6.5 million in past month. Out of these, 2 million Americans (aged 12 or older) either abused prescription drugs or were dependant on them. Almost 5% of adolescents (1.1 million) between the age group 12-17 abused prescription painkillers in 2014. Nationally, Kentucky is among the top five states with highest age-adjusted overdose …