Medicine and Health Sciences Commons^™

Conformational Altered P53 As An Early Marker Of Oxidative Stress In Alzheimer's Disease, Laura Buizza, Giovanna Cenini, Cristina Lanni, Giulia Ferrari-Toninelli, Chiara Prandelli, Stefano Govoni, Erica Buoso, Marco Racchi, Maria Barcikowska, Maria Styczynska, Aleksandra Szybinska, D. Allan Butterfield, Maurizio Memo, Daniela Uberti

Sanders-Brown Center on Aging Faculty Publications

In order to study oxidative stress in peripheral cells of Alzheimer's disease (AD) patients, immortalized lymphocytes derived from two peculiar cohorts of patients, referring to early onset AD (EOSAD) and subjects harboured AD related mutation (ADmut), were used. Oxidative stress was evaluated measuring i) the typical oxidative markers, such as HNE Michel adducts, 3 Nitro-Tyrosine residues and protein carbonyl on protein extracts, ii) and the antioxidant capacity, following the enzymatic kinetic of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRD). We found that the signs of oxidative stress, measured as oxidative marker levels, were evident only in ADmut …

Hiv-1 Tat Triggers Nuclear Localization Of Zo-1 Via Rho Signaling And Camp Response Element-Binding Protein Activation, Yu Zhong, Bei Zhang, Sung Yong Eum, Michal Toborek

Neurosurgery Faculty Publications

The human immunodeficiency virus (HIV)-specific protein trans-activator of transcription (Tat) can contribute to the dysfunction of brain endothelial cells and HIV trafficking into the brain by disrupting tight junction (TJ) integrity at the blood–brain barrier (BBB) level. Specific TJ proteins, such as zonula occludens (ZO) proteins, localize not only at the cell–cell borders but are also present in the nuclei. The objective of the present study was to evaluate the mechanisms and significance of Tat-induced nuclear localization of ZO-1. Treatment of a brain endothelial cell line (hCMEC/D3 cells) with Tat resulted in a decrease in total levels of ZO-1 but …

Food Store Environment Modifies Intervention Effect On Fruit And Vegetable Intake Among Low-Income Women In North Carolina, Alison A. Gustafson, Joseph Sharkey, Carmen D. Samuel-Hodge, Jessica C. Jones-Smith, Jianwen Cai, Alice S. Ammerman

Dietetics and Human Nutrition Faculty Publications

Background. The aim of the study is to determine how the food store environment modifies the effects of an intervention on diet among low-income women. Study Design. A 16-week face-to-face behavioral weight loss intervention was delivered among low income midlife women. Methods. The retail food environment for all women was characterized by (1) the number and type of food stores within census tracts; (2) availability of healthy foods in stores where participants shop; (3) an aggregate score of self-reported availability of healthy foods in neighborhood and food stores. Statistical Analyses. Multivariable linear regression was used to …

Atrazine Exposure In Public Drinking Water And Preterm Birth, Jessica L. Rinsky, Claudia Hopenhayn, Vijay Golla, Steven R. Browning, Heather M. Bush

Epidemiology and Environmental Health Faculty Publications

Objectives

Approximately 13% of all births occur prior to 37 weeks gestation in the U.S. Some established risk factors exist for preterm birth, but the etiology remains largely unknown. Recent studies have suggested an association with environmental exposures. We examined the relationship between preterm birth and exposure to a commonly used herbicide, atrazine, in drinking water.

Methods

We reviewed Kentucky birth certificate data for 2004–2006 to collect duration of pregnancy and other individual-level covariates. We assessed existing data sources for atrazine levels in public drinking water for the years 2000–2008, classifying maternal county of residence into three atrazine exposure groups. …

Role Of Community Health Workers In Improving Diabetes Outcomes, Janet Kegley, Helen Collett, Ralph Fugate

Center of Excellence in Rural Health Presentations

Objective Examine the effectiveness of using community health workers (CHWs) to support nurse-led diabetes self-management education (DSME) with medically underserved clients.

Methods A pretest-posttest group design was used. A sample of 640 was non-randomly drawn from eastern Kentucky Homeplace division clients who reported that they had been told by a health professional they have type-2 diabetes. The sample size for was reduced to 489 because of a decrease in project funding. Inclusion criteria for the study were Kentucky Homeplace clients 18-65+ years of age who reported they had been told by a provider they have diabetes. Clients meeting inclusion criteria …

From Service Provision To Function Based Performance - Perspectives On Public Health Systems From The Usa And Israel, F. Douglas Scutchfield, Ehud Miron, Richard Ingram

Preventive Medicine and Environmental Health Faculty Publications

If public health agencies are to fulfill their overall mission, they need to have defined measurable targets and should structure services to reach these targets, rather than offer a combination of ill-targeted programs. In order to do this, it is essential that there be a clear definition of what public health should do- a definition that does not ebb and flow based upon the prevailing political winds, but rather is based upon professional standards and measurements.

The establishment of the Essential Public Health Services framework in the U.S.A. was a major move in that direction, and the model, or revisions …

Polymorph Formation Of Tolfenamic Acid: An Investigation Of Pre-Nucleation Association, Alessandra Mattei

Theses and Dissertations--Pharmacy

The majority of pharmaceutical products are formulated as solids in the crystalline state. With the potential to exist in different crystalline modifications or polymorphs, each solid form bears its own physical and chemical properties, influencing directly bioavailability and manufacturability of the final dosage form. In view of the importance of crystalline form selection in the drug development process, it is imperative for pharmaceutical scientists to work arduously on various aspects of polymorphism, ranging from fundamental understanding of the phenomenon at the molecular level to practical utilization of a specific crystalline form. One common feature of organic crystals is the existence …

Regulation Of Platelet Exoctosis And Its Role In Diseases, Rania A. Al Hawas

Theses and Dissertations--Health and Clinical Sciences

In addition to their role in hemostasis, platelets appear to contribute to vascular inflammatory diseases. Platelets achieve this through the secretion of various prothrombotic and pro-inflammatory molecules. Platelet secretion is mediated by integral membrane proteins called Soluble NSF Attachment protein REceptors (SNAREs). SNAREs come from both granule/vesicle membranes (v-SNAREs) and target membranes (t-SNAREs) to form a trans-bilayer complex that promotes membrane fusion and subsequent granule cargo release. The work described in this dissertation dissects various, yet related aspects of platelet secretion in both physiological relevant and pathological circumstances.

Atherosclerosis is a leading cause of death in the westernized countries and …

Governance In Large Nonprofit Health Systems: Current Profile And Emerging Patterns, Lawrence Prybil, Samuel Levey, Rex Killian, David Fardo, Richard Chait, David R. Bardach, William Roach

Health Management and Policy Faculty Book Gallery

From the foreword:

Nonprofit healthcare organizations are not exempt from good governance. In fact, more today than ever, the hospitals and health care systems of this country must have the discipline and commitment to organize their governance structures and practices to provide forward-thinking leadership and stand up to scrutiny from any type of evaluation and review. As we move from “sick care” organizations to “health care” organizations with accountability for the health of the population of our communities from birth to end-of-life, the role of governance becomes even more critical.

Fourteen of the largest and most notable health care systems …

Relationship Between Physical Fitness Measures And Occupational Physical Ability In University Law Enforcement Officers, Annie Q. Beck

Theses and Dissertations--Kinesiology and Health Promotion

Law enforcement on academic campuses can be a physically demanding profession. Law enforcement officers (LEOs) may be required to perform a variety of physical tasks. Identifying which physical fitness characteristics are associated with these tasks will guide the development of appropriate and effective exercise programs. Therefore the purpose of this study was to identify physical fitness and demographic characteristics associated with the occupational physical ability of university LEOs. Sixteen male LEOs (age: 33.1±8.7 yr.; body mass: 87.2±11.2 kg; height: 178.9±7.9 cm) performed an officer physical ability test (OPAT) that simulated a foot chase of a suspect. In addition, the officers …

Sexually Transmitted Diseases (Stds), Donald E. Greydanus, Jane Seyler, Hatim A. Omar

Pediatrics Faculty Publications

High rates of unprotected sexual behavior in adolescents result in millions of cases of STDs in the world. This chapter reviews factors inducing high STD rates, specific STDs, and their management based on 2010 U.S. Centers for Disease Control and Prevention (CDC) STD guidelines. Clinicians should screen all their sexually active adolescent patients for STDs and provide preventive education as well as treatment measures.

Workers Die From Carbon Monoxide Poisoning, Kentucky Injury Prevention And Research Center

Kentucky Haz Alerts--Other

To prevent carbon monoxide poisoning,employers should:

• Train supervisors and employees to recognize symptoms of carbon monoxide poisoning
• Provide first aid training, including what to do if exposed to carbon monoxide
• Review carbon monoxide prevention tips with their employees

Employees should:

• Report unusual behavior
• Know how to treat co-workers for carbon monoxide poisoning
• Carry a carbon monoxide detector to mobile sites Recognize signs of carbon monoxide poisoning

Clinical Evaluation Of Novel Methods For Extending Microneedle Pore Lifetime, Nicole K. Brogden

Theses and Dissertations--Pharmacy

Microneedles are a minimally invasive method for delivering drugs through the impermeable skin layers, and have been used to deliver a variety of compounds including macromolecules, vaccines, and naltrexone. Microneedles can be applied to the skin once, creating micropores that allow for drug delivery into the underlying circulation from a drug formulation. The utility of this technique, however, is blunted by rapid micropore closure. This research project sought to: 1) characterize micropore lifetime and re-sealing kinetics, and 2) prolong micropore lifetime via inhibition of the skin’s barrier restoration processes. Impedance spectroscopy was used as a surrogate technique in animals and …

Identification Of Sumoylated Proteins And Investigation Of Protein Ubiquitination In The Nf-Κb Pathway, Xiaoyan Liu

Theses and Dissertations--Molecular and Cellular Biochemistry

SUMOylation and ubiquitination are important post-translational modifications. While ubiquitination is well known for targeting proteins for degradation, SUMOylation often regulates the intracellular localization of substrates. In the first project of this dissertation, we developed proteomic strategies to identify novel SUMOylated proteins in mammalian cells. In the second project, we investigated the regulation of protein ubiquitination in the NF-κB signaling pathway in the context of Paget’s disease of bone (PDB).

Identification of SUMOylated proteins has been a challenge because of low abundance of SUMOylation substrates. Here, we utilized a mass spectrometry (MS)-based proteomic approach to identify novel SUMOylated proteins in mammalian …

Decision-Making Processes And Health Behaviors Among Adults Diagnosed With Schizophrenia, Lillian J. Findlay

Theses and Dissertations--Nursing

Individuals diagnosed with schizophrenia commonly experience problems with accurately assessing their health status due to cognitive deficits including impaired working memory, amotivation, and communication difficulties. Little is known about whether these deficiencies influence health behavior decision-making among individuals with schizophrenia. Individuals with schizophrenia die an average of 25 years earlier than those without a mental illness. Approximately 60% of premature deaths in this population are from medical comorbidities; mortality rates due to cardiovascular and pulmonary diseases are two to three times higher than the general population. In order to reduce morbidity and mortality, it is important to find effective ways …

Characteristics Of All-Terrain Vehicles And Their Operators On Kentucky Farms, Jessica L. Wilson

Theses and Dissertations--Nursing

All-terrain vehicles (ATVs) were first developed and marketed in the U.S. in the 1970s. They have soared in popularity for occupational and recreational uses since that time. In 2008, there were approximately 10.2 million all-terrain vehicles (ATVs) in use in the United States. In 2001, it was estimated that 23 million Americans rode ATVs; 69% were adults and 31% children (CPSC, 2003). Deaths and injuries from ATVs have increased over time. According to the U.S. Consumer Product Safety Commission, Kentucky led the nation for ATV deaths from 2002-2006, with increasing numbers of fatalities annually.

ATV use on farms is increasing …

The Pharmacokinetics And Toxicology Of Aluminum In The Brain, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

The chemical forms (species) of aluminum in blood plasma and brain extracellular fluid are considered, as they are the candidates for brain aluminum uptake and efflux. The blood-brain barrier is the primary site of brain aluminum uptake. The mechanism of brain uptake of aluminum transferrin, long thought to be mediated by transferrin-receptor mediated endocytosis, requires further investigation. Brain Al citrate uptake has been attributed to the sodium-independent Lglutamate/ L-cystine exchanger system, system Xc-. Reports have suggested aluminum can compromise blood-brain barrier integrity, however the studies were conducted with aluminum concentrations greatly exceeding those seen in human blood plasma. Aluminum appeared …

Coplanar Pcb77 And Angii Induced Vascular Disorders, Madhura Parulkar

Theses and Dissertations--Nutritional Sciences

Previous studies demonstrated that coplanar PCBs promote inflammation by release of pro-inflammatory cytokines like TNF, MCP-1, and VCAM-1 from endothelial cells as well as adipocytes. Also these PCBs at small doses may contribute to the development of obesity by inducing adipocyte differentiation. Obesity is a known risk factor that promotes cardiovascular disorders like atherosclerosis and AAAs. Evidence shows Ang II, a component of the RAS, leads to the formation of atherosclerosis and AAAs in both normal as well as hyperlipidemic mice. Earlier studies in our laboratory have also shown that coplanar PCB-77 promotes atherosclerotic lesion formation in ApoE-/- mice. The …

Effects Of Adipocyte Deficiency Of Angiotensin Type 1a Receptors In Models Of Obesity And Hypercholesterolemia, Kelly Anne Putnam

Theses and Dissertations--Nutritional Sciences

Adipocytes express angiotensin II (AngII) receptors; however the direct effects of AngII at the adipocyte remain unclear. Knockout mouse models of renin-angiotensin system components exhibit reduced body weight, reduced adiposity, improved glucose tolerance, and improved blood pressure when fed high fat diets, which may be due to reduced action of AngII through the AT1aR in adipocytes. Additionally, hypercholesterolemic AT1aR deficient mice are protected from AngII-induced increases in atherosclerosis and abdominal aortic aneurysm (AAA) formation. We hypothesized that deficiency of AT1aR in adipocytes would reduce the development of obesity, obesity-induced disorders, and vascular diseases. To test this hypothesis, we created a …

5q Minus Myelodysplasia Associated With Multiple Epithelioid Granulomas Within Conventional Renal Cell Carcinoma, Rahul G. Matnani, Roshan K Patel, Stephen E Strup, Rouzan Karabakhtsian

Pathology and Laboratory Medicine Faculty Publications

A 69-year-old Caucasian female, with a previous diagnosis of 5q minus myelodysplastic syndrome, presented with conventional renal cell carcinoma (RCC) associated with multiple-epithelioid nonnecrotizing granulomas. Two previous reports of sarcoidosis, primarily involving the lung and skin, have been described in patients with 5q minus myelodysplasia. A cluster of closely linked genes encoding for cytokines such as IL-4, IL-5, and IL-3 are present on chromosome 5q. Hence, in sarcoidosis, cytokine imbalances associated with the deletion of these cytokine genes have been postulated. However, an occurrence of epithelioid granulomas within a carcinoma, in preexisting clonal myelodysplastic syndrome, has not been described. The …

Contraception In Adolescents, Donald E. Greydanus, Carolyn M. Lentzsch-Parcells, Hatim A. Omar

Pediatrics Faculty Publications

The age of adolescence is the time when most adolescents in the world begin to be sexually active with resultant millions of pregnancies and sexually transmitted diseases (STDs). This chapter considers methods of contraception for these adolescents, including oral contraceptives, transdermal contraception, minipills, intra-vaginal ring, injectable contraception, intrauterine devices (IUDs), barrier contraceptives, implants, and others. It is important for clinicians caring for sexually active youth to provide information regarding contraception and appropriate contraceptive prescriptions.

Contribution Of The Infection-Associated Complement Regulator-Acquiring Surface Protein 4 (Erpc) To Complement Resistance Of Borrelia Burgdorferi, Claudia Hammerschmidt, Teresia Hallström, Christine Skerka, Reinhard Wallich, Brian Stevenson, Peter F Zipfel, Peter Kraiczy

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Borrelia burgdorferi evades complement-mediated killing by interacting with complement regulators through distinct complement regulator-acquiring surface proteins (CRASPs). Here, we extend our analyses to the contribution of CRASP-4 in mediating complement resistance of B. burgdorferi and its interaction with human complement regulators. CRASP-4 (also known as ErpC) was immobilized onto magnetic beads and used to capture proteins from human serum. Following Western blotting, factor H (CFH), CFH-related protein 1 (CFHR1), CFHR2, and CFHR5 were identified as ligands of CRASP-4. To analyze the impact of native CRASP-4 on mediating survival of serum-sensitive cells in human serum, a B. garinii strain was generated …

Combination Effects Of Docetaxel And Doxorubicin In Hormone-Refractory Prostate Cancer Cells, Eleftheria Tsakalozou, Allison M. Eckman, Younsoo Bae

Pharmaceutical Sciences Faculty Publications

Combination effects of docetaxel (DOC) and doxorubicin (DOX) were investigated in prostate cancer cells (PC3 and DU145). Combination indices (CIs) were determined using the unified theory in various concentrations and mixing ratios (synergy: CI < 0.9, additivity: 0.9 < CI < 1.1, and antagonism: CI > 1.1). DOC showed a biphasic cytotoxicity pattern with the half maximal inhibitory concentration (IC50) at the picomolar range for PC3 (0.598 nM) and DU145 (0.469 nM), following 72 h drug exposure. The IC50s of DOX were 908 nM and 343 nM for PC3 and DU145, respectively. Strong synergy was seen when PC3 was treated with DOC at concentrations lower than its IC50 values (0.125~0.5 nM) plus …

Ceria-Engineered Nanomaterial Distribution In, And Clearance From, Blood: Size Matters, Mo Dan, Peng Wu, Eric A. Grulke, Uschi M. Graham, Jason M. Unrine, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

AIMS: Characterize different sized ceria-engineered nanomaterial (ENM) distribution in, and clearance from, blood (compared to the cerium ion) following intravenous infusion.

MATERIALS & METHODS: Cerium (Ce) was quantified in whole blood, serum and clot (the formed elements) up to 720 h.

RESULTS: Traditional pharmacokinetic modeling showed best fit for 5 nm ceria ENM and the cerium ion. Ceria ENMs larger than 5 nm were rapidly cleared from blood. After initially declining, whole blood 15 and 30 nm ceria increased (results that have not been well-described by traditional pharmacokinetic modeling). The cerium ion and 5 and 55 nm ceria did not …

Neuroangiogenesis: A Vascular Basis For Alzheimer's Disease And Cognitive Decline During Aging, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Angiogenesis directs development of the brain's microcirculation during antenatal and postnatal development, but its role later in life is less well recognized. I contend that during senescence a reduced cerebral capillary density accounts in part for the vascular cognitive impairment observed in many older persons and possibly for some forms of Alzheimer's disease. I propose that neuroangiogenesis is essential throughout adult life for maintaining the microcirculation of the cerebral cortex and elsewhere in the brain and that it commonly declines with old age. To support this hypothesis I have examined the neurological literature for relevant studies on cerebral capillary density …

Mnsod And Autophagy In Prevention Of Oxidative Mitochondrial Injuries Induced By Uvb In Murine Skin, Vasudevan Bakthavatchalu

Theses and Dissertations--Toxicology and Cancer Biology

UVB radiation is a known environmental carcinogen that causes DNA damage and increase ROS generation in mitochondria. Accumulating evidence suggests that mtDNA damage and increased ROS generation trigger mitochondrial translocation of p53. Within mitochondria, p53 interacts with nucleoid macromolecular complexes such as mitochondrial antioxidant MnSOD, mitochondrial DNA polymerase Polγ, and mtDNA. Mitochondria are considered to be a potential source for damage-associated molecular patterns (DAMPs) such as mtDNA, cytochrome C, ATP, and formyl peptides. Intracytoplasmic release of DAMPs can trigger inflammasome formation and programmed cell death processes. Autophagic clearance of mitochondria with compromised integrity can inhibit inflammatory and cell death processes. …

Lassa: Emotion Detection Via Information Fusion, Ning Yu, Sandra Kübler, Joshua Herring, Yu-Yin Hsu, Ross Israel, Charese Smiley

Information Science Faculty Publications

Due to the complexity of emotions in suicide notes and the subtle nature of sentiments, this study proposes a fusion approach to tackle the challenge of sentiment classification in suicide notes: leveraging WordNet-based lexicons, manually created rules, character-based n-grams, and other linguistic features. Although our results are not satisfying, some valuable lessons are learned and promising future directions are identified.

Age, Attention, And Ots In A Constrained Vs Unconstrained Task, Courtney Leann Jensen

Theses and Dissertations--Rehabilitation Sciences

The discourse of older healthy adults is commonly described as lengthy and off-topic and thought to be associated with a general cognitive decline that occurs in healthy aging. This study investigated the overall decline in attention associated with healthy aging and its relationship to instances of off-topic speech (OTS) in a constrained and unconstrained language production task. Ninety cognitively healthy adults participated and comprised three age cohorts (40 – 75+). Participants completed cognitive measures of attention and two discourse tasks that included recounting personal events and describing a procedure. Older adults exhibited poorer scores on measures of selective and shifting …

Serum Cartilage Oligomeric Matrix Protein: A Biomarker For Acute Articular Cartilage Damage, Johanna M. Hoch

Theses and Dissertations--Rehabilitation Sciences

Bone bruise lesions (BBL) are documented on MRIs diagnosing acute knee ligament injury (AKLI). Recent evidence has indicated that a majority of patients that sustain an AKLI, especially anterior cruciate ligament (ACL) knee injury, will develop post-traumatic osteoarthritis (PTOA) 10-20 years following injury. It has been proposed that the initial damage sustained to the articular cartilage overlying BBL causes a cascade of events that may result in PTOA.

Researchers have proposed a modification to treatment protocols for more severe BBL, or have stressed the need for the development of protective therapies to protect the articular cartilage. However, there are limited …

Developing A Model Of Client Satisfaction With A Rehabilitation Continuum Of Care, Melba G. Custer

Theses and Dissertations--Rehabilitation Sciences

Client satisfaction is an important outcome indicator because it measures multiple domains of the quality of healthcare and rehabilitation service delivery. It is especially important in occupational therapy because it is also client-centered. There are multiple domains of satisfaction and findings described in previous research; however, there is no single standard of measuring client satisfaction or any single working model describing the relationship among variables influencing satisfaction. This research was designed to apply a measure of satisfaction in rehabilitation and to develop a working model of satisfaction.

This study was an exploratory and predictive study using a large existing dataset …