Medicine and Health Sciences Commons^™

Role Of Pi3k-Akt Pathway In The Age Associated Decline In Tlr Mediated Activation Of Innate And Adaptive Immune Responses, Mosoka Papa Fallah

University of Kentucky Doctoral Dissertations

Immunosenescence results in reduced immune response to infections with Streptococcus pneumoniae as well as to pneumococcal polysaccharide vaccines. The antibody response to the capsular polysaccharide (CPS) provides protection against S. pneumoniae infection. CPS immunoresponse is T cell independent and needs the macrophage-derived cytokines such as IL-12, IL-6 and IL-1β to elicit an antibody response. We showed a cytokine dysregulation, i.e. a decrease in IL-12, IL-6 and TNF-α but an increase in IL-10, in the aged (18-24 months old comparable to >65 years in human) compared to young adult mouse (8-12 weeks less than 65 years old) splenic macrophages (SM) or …

Mobility, Balance, And Falls In Persons With Multiple Sclerosis, Jacob J. Sosnoff, Michael J. Socie, Morgan K. Boes, Brian M. Sandroff, John H. Pula, Yoojin Suh, Madeline Weikert, Steven Morrison, Robert W. Motl

Rehabilitation Sciences Faculty Publications

Background: There is a lack of information concerning the relation between objective measures of gait and balance and fall history in persons with MS (PwMS). This investigation assessed the relation between demographic, clinical, mobility and balance metrics and falls history in persons with multiple sclerosis (MS).

Methods: 52 ambulatory persons with MS (PwMS) participated in the investigation. All persons provided demographic information including fall history over the last 12 months. Disease status was assessed with Expanded Disability Status Scale (EDSS). Walking speed, coordination, endurance and postural control were quantified with a multidimensional mobility battery.

Results: Over 51% of the participants …

The Therapeutic Effects Upon Dog Owners Who Interact With Their Dogs In A Mindful Way, Amy Jackson-Grossblat

Dissertations

Problem. For many in contemporary culture, the pursuit of possession has become an attempt to achieve happiness. However, this path may not always be congruent with psychological well-being. In addition, this path may lead us further away from relationships within the natural world. Humanistic and existential psychologists have suggested that a mindful connection to ourselves, to other-than-human beings, and to the natural world would enable more meaningful lives. If dogs are considered an extension of nature and those interactions between dog and owner that promote mindfulness are examined, there is the potential to obtain a better understanding of how individuals …

Isolation And Elucidation Of The Chrysomycin Biosynthetic Gene Cluster And Altering The Glycosylation Patterns Of Tetracenomycins And Mithramycin-Pathway Molecules, Stephen Eric Nybo

University of Kentucky Doctoral Dissertations

Natural products occupy a central role as the majority of currently used antibiotic and anticancer agents. Among these are type-II polyketide synthase (PKS)-derived molecules, or polyketides, which are produced by many representatives of the genus Streptomyces. Some type-II polyketides, such as the tetracyclines and the anthracycline doxorubicin, are currently employed as therapeutics. However, several polyketide molecules exhibit promising biological activity, but due to toxic side effects or solubility concerns, remain undeveloped as drugs.

Gilvocarcin V (GV) (topoisomerase II inhibitor) has a novel mechanism of action: [2+2] cycloaddition to thymine residues by the 8-vinyl side chain and cross-linking of histone …

The Influence Of Antidiabetic Medications On The Development And Progression Of Prostate Cancer, Anna Elizabeth Hitron

University of Kentucky Master's Theses

The development of prostate tumors has been linked to co-morbid diabetes mellitus (DM) in several studies, potentially through the stimulation of insulin-like growth factor receptor (IGFR). This study evaluates the effect of anti-diabetic medication use on the development of high grade tumors and time to tumor progression compared to non-diabetics. This retrospective, nested case control study identified patients with prostate cancer (PCa) from the Kentucky Medicaid Database. Cases were diagnosed with PCa and DM and using at least one of the following antidiabetic medications; sulfonylureas, insulin, metformin or TZDs. Cases were further stratified on their insulin exposure resulting from therapy. …

Fairness-Trust-Loyalty Relationship Under Varying Conditions Of Supplier-Buyer Interdependence, Thani Jambulingam, Ravi Kathuria, John R. Nevin

Business Faculty Articles and Research

Relationship marketing plays a significant role in supply chain practice and academic studies. Using the resource advantage theory within the relationship marketing framework, we studied the mediating role of trust as a governance mechanism in the fairness-loyalty relationship under different types of interdependence structure between suppliers (wholesalers) and buyers (retailers). Our findings, based on data from retail pharmacies, demonstrate that only under conditions of symmetric independence, trust, as a governance mechanism, completely mediate the relationship between fairness and loyalty. Under conditions of both perceived independence (i.e., lack of interdependence) and asymmetric buyer dependence, however, trust does not mediate but fairness …

Effects Of Lateral Ligament Sectioning On The Stability Of The Ankle And Subtalar Joint, Stacie I. Ringleb, Ajaya Dhakal, Claude D. Anderson, Sebastian Bawab, Rajesh Paranjape

Mechanical & Aerospace Engineering Faculty Publications

Patients with subtalar joint instability are often diagnosed with ankle instability. Only after a prolonged period of time in which a patient does not improve after treatment for ankle instability is subtalar joint instability considered. To develop a clinically relevant method to diagnose subtalar joint instability, the kinematics of the simulated unstable subtalar joint were examined. A 6 degree-of-freedom positioning and loading device was developed. Plantarflexion/dorsiflexion, inversion/eversion, and internal/external rotation were applied individually or as coupled motions along with an anterior/posterior drawer. Kinematic data were collected from sensors attached to the calcaneus, talus, and tibia by keeping all the ligaments …

Evaluation Of Capacity For Best Practice Of Clinical Vaccine Research In Western Kenya, Sylvie Anne Kwedi

Walden Dissertations and Doctoral Studies

African institutions that perform health research need to continuously evaluate their practices in order to ensure compliance with international standards of good clinical practice (GCP). This mixed-methods study, undertaken at one clinical research site in Western Kenya, was an evaluation of GCP compliance at the site, research participants' satisfaction with research procedures, and research participants' comprehension of informed consent. The qualitative portion of the study involved audit of the site's compliance with GCP standards. The quantitative portion was an assessment of participant satisfaction and informed consent comprehension, undertaken through interviews with a sample of 297 participants. Thematic analysis of the …

Effect Of Stress, Emotional Lability And Depression On The Development Of Pregnancy Complications, Servitje, Estibalitz Laresgoiti Servitje

Walden Dissertations and Doctoral Studies

Chronic stress and other emotional factors may have relevant impacts on pregnancy outcomes because they are related to neuroendocrine changes that lead to alterations in immunomodulation during pregnancy. In this quantitative prospective cross-sectional study, the relationship of emotional lability, depression, and stress during pregnancy and the development of preterm labor, preeclampsia, placental abruption, and low birth weight for gestational age babies was examined. Additionally, social support scores were compared to levels of stress/anxiety, depression, and emotional lability in pregnant women. Two hundred and forty two pregnant women who received prenatal services at the National Institute of Perinatology in Mexico City …

1st Place: "Co-Production: A Scientific Approach To The Humanities", Kirsten Moore

John and Margaret Class Student Book Collection Contest

This is Kirsten Moore's submission essay, annotated bibliography, and annotated wishlist for the 2010-2011 John and Margaret Class Student Book Collection Contest, which won first place.

Management Of Decubitus Ulcer Using Gentamycin Sulphate Iontophoresis - A Case Study, Ayodele Teslim Onigbinde, Kehinde Foyeke Olafimihan, Adesola Ojoawo, Joyce Mothabeng, Olufemi Opeyemi Ogundiran

Internet Journal of Allied Health Sciences and Practice

Most infective organisms have developed resistance against antibiotics. There is need to find other means to deliver antibiotics locally. There appears to be limited studies on the use of gentamicin sulphate iontophoresis in wound management. The participant in this study was a subject diagnosed with mild head injury secondary to motor vehicle accident who later developed a unilateral pressure sore on the left gluteal region. The subject received 15-minutes of gentamicin sulphate iontophoresis (Interrupted Direct Current) three times a week for five weeks. The case report showed that there was a 65.7% reduction in wound surface area of the decubitus …

Exercise Habits And Tobacco Use Among Male Latino Farmworkers, Jason Brumitt, Leda I. Garside, Rebecca Reisch, Talina Marshall, Hui En Gilpin, Jessica Kinsey, Kelsey Imondi, Heather Robinson

Faculty Publications - College of Physical Therapy

Migrant farmworkers risk occupational injury and are at risk for developing chronic health conditions. Exercise may enhance health and help to reduce the risk of occupational injury and/or reduce the risk of developing a chronic health condition. Little is known, however, about the exercise habits of Latino migrant farmworkers. Male Latino migrant farmworkers completed an exercise and health habits questionnaire at health screening clinics. One hundred fifty-three (58.2%) subjects reported exercising during the week. There was no difference in age between those who reported exercising and those who did not (p = .78). Only 42 (16%) of all workers reported …

Self-Reported Musculoskeletal Pain In Latino Vineyard Workers, Jason Brumitt, Rebecca Reisch, Karla Krasnoselsky, Amy Welch, Richard Rutt, Leda I. Garside, Carolyn Mckay

Faculty Publications - College of Physical Therapy

The agricultural economy in the United States is dependent on millions of Latino migratory workers. Despite the health risks associated with this line of work, many agricultural workers lack health insurance or access to health care services. The purpose of this study was to collect demographic data and investigate the musculoskeletal health of Latino migratory vineyard workers. A physical therapy team collected demographic data at health clinics held at vineyards in Oregon. Nearly half (48.4%) of all vineyard workers reported experiencing musculoskeletal symptoms (MSS) in at least one region of the body. The primary region of reported MSS was the …

Summary Of Findings Health Status Of Children Entering Kindergarten: Results Of The 2010-2011 (Year Three) Nevada Kindergarten Health Survey, Nevada Institute For Children's Research And Policy Reports

Nevada Institute for Children's Research and Policy Reports

Academic achievement for children is vital to their success in life. Those that do well in school have greater opportunities for post-secondary education, and later have better prospects for employment. One of the major factors that can affect a child’s academic achievement is his or her health status. Academic outcomes and health conditions are consistently linked in the literature (Taras & Potts-Datema, 2005). Children with poor health status, and especially those with common chronic health conditions, have increased numbers of school absences and more academic deficiencies (Taras & Potts-Datema, 2005). In a study concerning excused versus unexcused absences, children with …

Lipopolysaccharide Animal Models For Parkinson's Disease, Mei Liu, Guoying Bing

Neuroscience Faculty Publications

Lipopolysaccharide (LPS), an endotoxin from Gram-negative bacteria, acts as a potent stimulator of microglia and has been used to study the inflammatory process in the pathogenesis of Parkinson's disease (PD) and anti-inflammatory therapy for PD treatment. Here, we review the growing body of literature on both in vitro and in vivo LPS PD models. Primary cell cultures from mesencephalic tissue were exposed to LPS in vitro; LPS was stereotaxically injected into the substantia nigra, striatum, or globus pallidus of brain or injected into the peritoneal cavity of the animal in vivo. In conclusion, the LPS PD models are summarized as …

Current Review Of In Nivo Gbm Rodent Models: Emphasis On The Cns-1 Tumour Model, Valerie L. Jacobs, Pablo A. Valdes, William F. Hickey, Joyce A. De Leo

Dartmouth Scholarship

GBM (glioblastoma multiforme) is a highly aggressive brain tumour with very poor prognosis despite multi-modalities of treatment. Furthermore, recent failure of targeted therapy for these tumours highlights the need of appropriate rodent models for preclinical studies. In this review, we highlight the most commonly used rodent models (U251, U86, GL261, C6, 9L and CNS-1) with a focus on the pathological and genetic similarities to the human disease. We end with a comprehensive review of the CNS-1 rodent model.

A Retinoic Acid–Dependent Checkpoint In The Development Of Cd4+ T Cell–Mediated Immunity, Karina Pino-Lagos, Yanxia Guo, Chrysothemis Brown, Matthew P. Alexander, Raúl Elgueta, Kathryn A. Bennett, Victor De Vries, Elizabeth Nowak, Rune Blomhoff, Shanthini Sockanathan, Roshantha A. Chandraratna, Ethan Dmitrovsky, Randolph J. Noelle

Dartmouth Scholarship

It is known that vitamin A and its metabolite, retinoic acid (RA), are essential for host defense. However, the mechanisms for how RA controls inflammation are incompletely understood. The findings presented in this study show that RA signaling occurs concurrent with the development of inflammation. In models of vaccination and allogeneic graft rejection, whole body imaging reveals that RA signaling is temporally and spatially restricted to the site of inflammation. Conditional ablation of RA signaling in T cells significantly interferes with CD4⁺ T cell effector function, migration, and polarity. These findings provide a new perspective of the role of …

Mitochondria, Amyloid Β, And Alzheimer's Disease, Ryan Douglas Readnower, Andrew David Sauerbeck, Patrick G. Sullivan

Spinal Cord and Brain Injury Research Center Faculty Publications

Hypometabolism is a hallmark of Alzheimer's disease (AD) and implicates a mitochondrial role in the neuropathology associated with AD. Mitochondrial amyloid-beta (Aβ) accumulation precedes extracellular Aβ deposition. In addition to increasing oxidative stress, Aβ has been shown to directly inhibit mitochondrial enzymes. Inhibition of mitochondrial enzymes as a result of oxidative damage or Aβ interaction perpetuates oxidative stress and leads to a hypometabolic state. Additionally, Aβ has also been shown to interact with cyclophilin D, a component of the mitochondrial permeability transition pore, which may promote cell death. Therefore, ample evidence exists indicating that …

Expedient Treatment Of A Collodion Baby, Michael Chung, Jaime Pittenger, Stuart Tobin, Andrew Chung, Nirmala Desai

Pediatrics Faculty Publications

Only ~270 cases of collodion babies have been reported in the literature since 1892. As the name suggests, the term "collodion baby" refers to a phenotype that can be characterized by a yellow, shiny, tight parchment-like membrane stretched over the skin. Although the collodion membrane is only an evanescent condition of the newborn, neonatal complications can occur in 45% of all collodion babies, leading to a mortality rate of ~11% in the first few weeks of life. Most children born as collodion babies will spontaneously desquamate within 2 weeks, but may be as long as 3 months. Eventually, these children …

Role Of Vascular Endothelial Growth Factor, Placental Growth Factor And Cytokines On Outer Blood Retinal Barrier Breakdown., Sangeetha Sukumaran

Masters

The aim of this thesis was to investigate the effect of the VEGF family of growth factors and
cytokines TNF- α and IL-1β on oBRB function. The human RPE line ARPE-19 was
employed as an in vitro model of the oBRB. Two-Dimensional gel electrophoresis was
employed to study the effect of growth factors on the RPE proteome. The barrier properties of
the oBRB were evaluated by expression of the TJ proteins occludin or Zo-1, or claudins-1, 2,
3 and 4, determined by western blotting analysis. Claudins 2, 3 and 4 were found to be
significantly up-regulated by TNF-α, while interleukin …

Composition - Structure - Property Relationships In Strontium / Zinc Doped Glass-Ceramics., Mark Looney

Theses

Calcium silicate ceramics are amongst a group of ceramic materials currently utilised as bone graft materials. However, current calcium silicate grafts offer little therapeutic potential and poor mechanical properties. The objective of this project was to examine the composition-structure-property relationships arising from the incorporation of therapeutic ions of strontium (Sr) and zinc (Zn) into calcium silicate glass-ceramics (GC) in order to allow for healthy bone regeneration and antibacterial efficacy. Five compositions were studied with varying mole fractions of Sr and Zn. The GC’s were characterised using differential scanning calorimetry (DSC), x-ray diffraction (XRD) at room and ascending temperatures, x-ray tomography …

Integrating Education, Group Support, And Case Management For Diabetic Hispanics, Sharon A. Brown, Alexandra A. García, Mary Winter, Lita Silva, Adama Brown, Craig Hanis

School of Nursing Faculty Publications

Objectives: Culturally tailored diabetes self-management education (DSME) improves glycemic control and other health outcomes in Mexican Americans but sociocultural barriers to health improvements remain. This study explored the feasibility of adding a nurse case manager (NCM) to DSME to foster DSME attendance and increase utilization of other available health care services.

Design, setting and participants: The setting was a rural community on the Texas-Mexico border in one of the poorest counties in the United States. Using a repeated measures pretest, post-test control group design, we enrolled 165 Mexican American adults into: 1) an experimental group that received a DSME intervention …

Part A: Studies Towards Total Synthesis Of An Anticancer And Antifungal Natural Product, Pseudolaric Acid B; Part B: Synthesis And Biological Evaluation Of Berkeleyamide A And Its Derivatives, Swapnil Jayant Kulkarni

Electronic Theses and Dissertations

Part A: Studies towards total synthesis of an antifungal and anticancer agent, Pseudolaric acid B. Marked by the uncontrolled cell proliferation, cancer is one of the deadliest diseases, accounting for about 7.0 million deaths in 2007. Cancer is second leading cause of death worldwide, according to the American Cancer Society. Cancer chemotherapy has evolved through many years of painstaking research, and as a result, today we are able to cure at least some of cancers. One of the major impediments in the development of new drugs for treating cancer is that most of the approved drugs are themselves toxic and …

Avian Cerebellum Specialization In Relation To Acrobatic Courtship Displays In Manakins (Pipridae), Steven Ray Wilkening

Electronic Theses and Dissertations

The courtship displays of male manakins (Pipridae) involve an array of acrobatic and postural elements. Previously it was found that species with elaborate displays exhibit specializations in motor planning and coordination areas of the brain. Several studies have suggested a relationship between cerebellum (Cb) morphology and distinct motor-related functions for the anterior Cb (somatosensory, flying, hopping/walking), posterior Cb (vision, audition, flying, hopping/walking), and vestibular Cb (flying, hopping/walking, vestibular). The anterior, posterior and vestibular Cb as well as basic morphological features of the Cb were measured and tested for a relationship with courtship display complexity in manakins. I compared Cb morphology …

Factors Associated With Tobacco Use Among Rural And Urban Pregnant Women, Whitney Jeanne Katirai

University of Kentucky Doctoral Dissertations

The purpose of this study was to investigate the influences of smoking on rural and urban pregnant women. More specifically, the variables of the knowledge of health effects, health provider recommendations, subscores from the Health Belief Model (HBM), and social support were explored in relation to the smoking behavior of pregnant women. A secondary purpose was to investigate the accuracy of self-reported smoking during pregnancy using biochemical validation. Pregnant women (N=71) completed an anonymous questionnaire, designed by the researcher, to identify variables that predicted smoking for urban and rural women. Participants also gave a saliva sample for cotinine testing.

Approximately …

Genotoxin-Induced Acetylation Of The Werner Syndrome Protein (Wrn) And Effect On Its Dna Metabolic Function, Enerlyn Meliza Lozada Santiago

University of Kentucky Doctoral Dissertations

Loss of function of the WRN protein causes the genetic disorder Werner Syndrome that is characterized by increased cancer and premature aging. WRN belongs to the RecQ helicase family that plays key roles in preventing genome instability. In response to treatment with genotoxins, WRN is subject to post-translational modification. The relationship of post-translational modification of WRN with its function in DNA metabolism is unknown. There is accumulating evidence suggesting that WRN contributes to the maintenance of genomic integrity through its involvement in DNA replication. Consistent with this notion, WS cells are sensitive to DNA replication inhibitors and DNA damaging agents …

Effect Of Azithromycin On Macrophage Phenotype During Pulmonary Infections And Cystic Fibrosis, Theodore James Cory

University of Kentucky Doctoral Dissertations

Azithromycin improves clinical outcomes in patients with cystic fibrosis (CF), specifically in patients infected with Pseudomonas aeruginosa. Azithromycin shifts macrophage programming away from a pro-inflammatory classical (M1) phenotype, and towards an anti-inflammatory alternative (M2) phenotype; however, little is known about this mechanism, nor of its impact upon immune response to pulmonary infection. We set out to determine the mechanism by which azithromycin is able to alter macrophage phenotype, and assess the effect of azithromycin induced macrophage polarization on inflammation during pulmonary infections.

Utilizing macrophage cell culture, we found that azithromycin increased IKKβ, a signaling molecule in the NFκB pathway, which …

Molecular And Genomic Approaches To Understanding Host-Virus Interactions In Shaping The Outcome Of Equine Arteritis Virus Infection, Yun Young Go

University of Kentucky Doctoral Dissertations

Equine arteritis virus (EAV) is the causal agent of equine viral arteritis, a disease of equids. During natural outbreaks of the disease, EAV can cause abortion in pregnant mares and persistent infection in stallions. Understanding how host cellular proteins interact with viral RNA and viral proteins, as well as their role in viral infection, will enable better characterization of the pathogenesis of EAV and establishment of persistent infection in stallions. Accordingly, we hypothesized that both viral factors and host genetically related factors could influence the outcome of EAV infection in horses. To test this hypothesis, we first combined contemporary molecular …

Polyamine Modulation In Alcoholism: Examination Using A Novel Screening Procedure Designed To Predict Anti-Relapse And Neuroprotective Efficacy, J. Ben Lewis

University of Kentucky Doctoral Dissertations

Alcohol dependence is a major public health concern. Despite the FDA’s approval of multiple anti-relapse drugs, relapse rates remain unacceptably high. Furthermore, cognitive deficits among chronic drinkers are evident and are suggested to contribute to relapse risk. Current evidence suggests that several critical features of alcoholism and alcohol-associated neurodegeneration are mechanistically linked to glutamatergic actions; specifically, they appear positively affected by glutamatergic inhibition, particularly inhibition via polyamine modulation of a subpopulation of n-methyl-d-aspartate receptors. The current project was designed to evaluate the performance of two putative polyamine modulators (JR-220 and CP-101,606) in a variety of screens designed …

The Effect Of Two Different Implant Systems On Bony Changes In Mandibular Implant Supported Overdenture, Fardos N. Rizk, Eatmad Elrekaby, Azza Farahat

Dentistry

objective: This study was conducted to evaluate the bone changes that may occur around Legacy I implants and NanoTite Tapered implants supporting mandibular overdentures utilizing cone beam computed tomography (CBCT). materials and methods: Fourteen completely edentulous male patients were randomly divided into two equal groups. Group I: Each patient received two Legacy I implants. Group II: Each patient received two NanoTite Tapered Implants. All implants were inserted bilaterally in the mandibular canine region. For all patients conventional complete dentures were constructed before implants placement. After complete osseointegration of implants, dome shaped healing collars were screwed to the implants upon which …