Abc Transporters In Glioblastoma: Anticancer Drug Transport And Transporter Regulation At The Blood-Brain Barrier, Julia A. Schulz

Theses and Dissertations--Pharmacy

Glioblastoma is one of the deadliest cancers, with a median survival of only one year. Even after aggressive treatment consisting of surgical resection, radiation, and chemotherapy, most glioblastoma patients suffer from tumor recurrence within 6-9 months. One reason for treatment failure of anticancer drugs is the blood-brain barrier that protects the brain by impeding xenobiotic uptake from the blood. To this end, efflux transporters at the human blood-brain barrier, such as P-glycoprotein (ABCB1) and Breast Cancer Resistance Protein (ABCG2), prevent many compounds, including anticancer drugs, from entering the brain. Thus far, approaches to deliver anticancer drugs across the blood-brain barrier …

Identification And Characterization Of Epitope Specific Immune Responses In Humans And Mice, David Henson

Theses and Dissertations--Pharmacy

Cardiovascular disease (CVD) is a major cause of morbidity and mortality around the world causing approximately 14% of total disease burden. A major factor in the progression to major CVD within patients is immune activation, which led to the study of various immune products as potential biomarkers for the prediction of cardiovascular events, including antigen-specific antibodies and immune complexes. One focus of this biomarker research is IgG autoantibodies targeting apolipoprotein A-I (ApoA-I), and several studies of these antibodies have found an association with increased CVD events. Based on the encouraging results from these studies and previous research which has identified …

Therapeutic Drug Monitoring Of Beta-Lactam Antibiotics In Critically Ill Patients With Sepsis, Melissa Thompson Bastin

Theses and Dissertations--Clinical and Translational Science

Sepsis is a devastating diagnosis affecting over 750,000 patients a year, accounting for approximately 10% of all hospital admissions, costs more than $50,000 per patient, and exceeds $17 billion annual spending. The mortality rate for sepsis remains unacceptably high: one out of every three patients diagnosed with sepsis dies. Sepsis physiology induces physiologic changes to drug pharmacokinetic (PK) parameters that alter the ability to achieve the goal pharmacodynamic (PD) target for beta-lactams of >4-fold unbound concentration above the minimum inhibitory concentration for 100% of the dosing interval (100% fT >4x MIC). Sepsis treatment such as volume resuscitation and vasopressor …

The Gestation Of Health: Environmental Insults, Behavioral Interventions, And Protective Mechanisms, Brittany Breon Rice

Theses and Dissertations--Pharmacology and Nutritional Sciences

Diabetes remains a leading cause of death nationwide despite pharmacological advances. Recent etiological investigations of the disease detail the role of perinatal exposure to environmental contaminants, such as polychlorinated biphenyls (PCBs), in enhancing disease susceptibility. Polychlorinated biphenyl 126, a coplanar PCB, elicits its toxic effects through the aryl-hydrocarbon receptor and the disruption of endocrine signaling. The goal of this dissertation was to focus on delineating the differences in the developmental windows of diabetes susceptibility respective to the timing of PCB126 exposure and to understand the influence of maternal exercise and nuclear-factor erythroid-2-related factor 2 (Nrf2) expression in combating the negative …

The Role Of Microtubule-Associated Protein Tau In Neuronal Excitability And Epileptogenesis, Ryan A. Cloyd

Theses and Dissertations--Physiology

Tauopathies, including Alzheimer’s disease (AD), are devastating diseases with an immense burden on society which is predicted to increase in coming decades. In addition to progressive loss of memory and cognitive function, patients with tauopathies have a 6-10 fold increase in lifetime risk for seizures, and many are diagnosed with epilepsy. The presence of epileptiform activity on electroencephalogram (EEG) recordings from patients with AD predicts faster cognitive decline compared to patients without abnormal EEG readings. Electrophysiological measurements in murine models of AD have identified neuronal hyperexcitability. Furthermore, reducing tau phosphorylation or expression confers seizure resistance in animal epilepsy models. Although …

An Assessment Of The Carrier State And A Novel Marker Of Leptospira And Abortion In Central Kentucky Horses, Gloria Louise Gellin

Theses and Dissertations--Veterinary Science

Leptospirosis is a reemerging zoonotic infection of worldwide importance and affects all mammals. The bacterium is transmitted to animals and humans by urine, fetal membranes and body fluids. Leptospira shedding in the urine contaminates both soil and water, exposing both humans and animals to the bacterium. Leptospirosis in horses can cause abortion and is one of the etiologies of equine recurrent uveitis which can lead to blindness. Equine leptospiral abortion in Central Kentucky is primarily caused by serovar Pomona, with occasional cases attributed to serovar Grippotyphosa. There are a few reports in the literature attributing abortion to serovar Bratislava in …

Oat Intake And Risk Of Type 2 Diabetes, Cardiovascular Disease And All-Cause Mortality: A Systematic Review And Meta-Analysis, Faina Wehrli, Petek E. Taneri, Arjola Bano, Lia Bally, Lauren C. Blekkenhorst, Weston Bussler, Brandon Metzger, Beatrice Minder, Marija Glisic, Taulant Muka, Hua Kern

Research outputs 2014 to 2021

Cardiovascular disease (CVD) and type 2 diabetes (T2D) remain the top disease and mortality burdens worldwide. Oats have been shown to benefit cardiovascular health and improve insulin resistance. However, the evidence linking oat consumption with CVD, T2D and all-cause mortality remains inconclusive. We conducted a comprehensive systematic review and meta-analysis of prospective cohort studies to evaluate the associations between oat consumption and risks of T2D, CVD and all-cause mortality in the general population. Five electronic databases were searched until September, 2020. Study specific relative risks (RR) were meta-analyzed using random effect models. Of 4686 relevant references, we included 9 articles, …

Actividades Profesionales Reservadas En Argentina: Orígenes Y Actualidad / Reserved Professional Activities In Argentina: Origins And Current Situation, Cintia E. Citterio, Héctor Targovnik

Pharmacy Faculty Articles and Research

En Argentina, la Ley de Educación Superior (LES; Ley 24.521, 1995) establece que hay profesiones cuyo ejercicio puede comprometer el interés público poniendo en riesgo de modo directo la salud, la seguridad, los derechos, los bienes o la formación de los habitantes, y las mismas están contempladas en el artículo 43 de la LES. Sólo aquellas actividades que realicen estos profesionales y que implican un riesgo rigurosamente directo, se denominan actividades profesionales reservadas. Pero… ¿Cuál es la diferencia entre actividades profesionales reservadas y alcances de los títulos? ¿Y cómo se establecen? El objetivo de este trabajo es analizar el significado …

A Case Report Discussing An Uncommon Peripheral Exudative Hemorrhagic Chorioretinopathy, Marlon J. Demeritt, Beata I. Lewandowska

Internet Journal of Allied Health Sciences and Practice

Purpose: The purpose of this case report is to discuss an uncommon, unique hemorrhagic chorioretinopathy. Method: A 79-year-old-white female presented to clinic with complaints of difficulty reading at close distances and seeing faces at far distances in both eyes. An 85-year old white female presented with no visual complaints but stated redness in the nasal corner of her right eye. This is a case report of two patients that presented with geographic atrophy of the macula as well as midperipheral RPE alterations in both eyes, which resembled intraretinal hemorrhages. Results: The ocular findings associated with peripheral exudative hemorrhagic chorioretinopathy may …

Novel Mechanistic Insights Towards The Repositioning Of Alogliptin In Parkinson's Disease, Eman Ramadan, Marwa M. Safar

Pharmacy

Parkinson's disease (PD) is a progressive neurodegenerative disease that impairs people's lives tremendously. The development of innovative treatment modalities for PD is a significant unmet medical need. The critical function of glucagon-like peptide-1 (GLP-1) in neurodegenerative diseases has raised impetus in investigating the repositioning of a dipeptidyl peptidase IV inhibitor, alogliptin (ALO), as an effective treatment for PD. As a result, the focus of this research was to assess the effect of ALO in a rat rotenone (ROT) model of PD. For 21 days, ROT (1.5 mg/kg) was delivered subcutaneously every other day. ALO (30 mg/kg/day), delivered by gavage for …

Management Of Refractory Ventricular Fibrillation With Double Sequential Defibrillation, Kaitlyn A. Brown

Capstone Showcase

Patients experiencing cardiac arrest are treated according to ACLS protocols, however current protocols lack recommendations for the treatment of refractory Ventricular Fibrillation which persists after more than 3 cycles of CPR and defibrillation. One potential intervention for these cases that is being researched is the use of simultaneous or sequential activation of two defibrillators. This literature review analyzed the results of several studies to determine if double sequential defibrillation (DSD) is a viable treatment to achieve return of spontaneous circulation (ROSC) and improved patient survival. The results of the studies were mixed with some showing positive outcomes, and others showing …

Rad Modulation Of The L-Type Calcium Channel Confers Systolic Advantage In The Heart, Brooke Mildred Ahern

Theses and Dissertations--Physiology

Heart failure is a major public health problem and a leading cause of mortality. This clinical condition affects populations of all ages, and is the result of various cardiomyopathies. Almost half of these patients suffer specifically from heart failure with reduced ejection fraction; these hearts have decreased performance due to a failure of the heart to contract with sufficient force to meet demand. While there are therapies available to increase contractility, none of these enhance contraction without also further promoting pathological signaling and remodeling.

Under normal physiological conditions, the body elevates cardiac output through the fight-or-flight response. This response activates …

Short-Range Forecasting Of Covid-19 During Early Onset At County, Health District, And State Geographic Levels Using Seven Methods: Comparative Forecasting Study, Christopher Lynch, Ross Gore

VMASC Publications

BACKGROUND:

Forecasting methods rely on trends and averages of prior observations to forecast COVID-19 case counts. COVID-19 forecasts have received much media attention, and numerous platforms have been created to inform the public. However, forecasting effectiveness varies by geographic scope and is affected by changing assumptions in behaviors and preventative measures in response to the pandemic. Due to time requirements for developing a COVID-19 vaccine, evidence is needed to inform short-term forecasting method selection at county, health district, and state levels.

OBJECTIVE:

COVID-19 forecasts keep the public informed and contribute to public policy. As such, proper understanding of forecasting purposes …

A White Matter Connection Of Schizophrenia And Alzheimer’S Disease, Peter Kochunov, Artemis Zavaliangos-Petropulu, Neda Jahanshad, Paul M. Thompson, Meghann C. Ryan, Joshua Chiappelli, Shuo Chen, Xiaoming Du, Kathryn Hatch, Bhim Adhikari, Joanne E. Curran, John Blangero

School of Medicine Publications

Schizophrenia (SZ) is a severe psychiatric illness associated with an elevated risk for developing Alzheimer’s disease (AD). Both SZ and AD have white matter abnormalities and cognitive deficits as core disease features. We hypothesized that aging in SZ patients may be associated with the development of cerebral white matter deficit patterns similar to those observed in AD. We identified and replicated aging-related increases in the similarity between white matter deficit patterns in patients with SZ and AD. The white matter “regional vulnerability index” (RVI) for AD was significantly higher in SZ patients compared with healthy controls in both the independent …

Another One Bites The Joint: A Case Of Reactive Arthritis In An Otherwise Healthy Hispanic Male, Christine E. Loftis, Emilia C. Dulgheru

School of Medicine Publications

Reactive Arthritis is a spondyloarthritis following gastrointestinal or genitourinary infections, traditionally described as a triad of conjunctivitis, urethritis, and arthritis. It is important to identify patients with reactive arthritis as certain disease features portend a poorer prognosis. We present a case of reactive arthritis in a 36-year-old gentleman after a self-limited episode of gastroenteritis.

A 36-year-old man presented to the Rheumatology clinic for a 2-week history of multiple arthralgias. The patient reported that one week before the onset of arthritis he experienced a self-limited episode of gastroenteritis. Succeeding, the patient noticed pain and swelling to right wrist, left elbow, and …

Association Of Fatal And Nonfatal Cardiovascular Outcomes With 24-Hour Mean Arterial Pressure, Jesus D. Melgarejo, Wen-Yi Yang, Lutgarde Thijs, Kei Asayama, Tine W. Hansen, Fang-Fei Wei, Masahiro Kikuya, Takayoshi Ohkubo, Eamon Dolan, Gladys E. Maestre

School of Medicine Publications

Major adverse cardiovascular events are closely associated with 24-hour blood pressure (BP). We determined outcome-driven thresholds for 24-hour mean arterial pressure (MAP), a BP index estimated by oscillometric devices. We assessed the association of major adverse cardiovascular events with 24-hour MAP, systolic BP (SBP), and diastolic BP (DBP) in a population-based cohort (n=11 596). Statistics included multivariable Cox regression and the generalized R2 statistic to test model fit. Baseline office and 24-hour MAP averaged 97.4 and 90.4 mm Hg. Over 13.6 years (median), 2034 major adverse cardiovascular events occurred. Twenty-four-hour MAP levels of <90 >(normotension, n=6183), 90 to <92 >(elevated MAP, n=909), …

Addressing Health-Related Myths In The Culturally Diverse African American Population: A Call To Action, Lucson Joseph

Internet Journal of Allied Health Sciences and Practice

African Americans (AAs) experience numerous challenges that socially, economically, and physically affect their communities. Recent studies have found that a diverse array AAs encounter many struggles as they navigate the United States (U.S.) healthcare system to access care and receive healthcare services. AA communities are significantly affected by the burden of chronic diseases. They face considerable barriers to healthcare services that contribute to adverse health outcomes. This paper explains the daily struggles many AAs face within their communities to access and navigate the healthcare system due to culturally held myths and barriers. This paper discusses commonly held myths among Afro-Caribbean …

Sars-Cov-2: An Investigation On Mutagenicity And Its Effects On Infectivity And Mortality, Tyler Elliott Silverwood

Honors Theses and Capstones

SARS-CoV-2, the etiological agent of the COVID-19 pandemic, has rapidly become a worldwide public health concern. Classified as a betacoronavirus, it is the third human coronavirus (HCoV) to emerge in the 21st century that causes severe disease, alongside SARS-CoV and MERS-CoV. The genome consists of open reading frames encoding accessory proteins and four structural proteins, including the spike protein which is a key determinant of host cell tropism. Mutations within the genome, particularly the spike gene, have been linked in-vitro to increased binding affinity to the human receptor angiotensin-converting enzyme 2 (hACE2), increased fitness in human hosts, and immune evasion. …

Cold-Induced Metabolic Changes In Lean, Nag-1 Transgenic Mice, Rachel J. Davey

All Master's Theses

Obesity is a multifaceted metabolic disorder with severe worldwide public health consequences. While obesity can often be treated using diet and exercise, there are complex genetic interactions driving obesity that don’t always respond to such changes. One important research focus for addressing genetic factors is activating brown adipose tissue which increases thermogenesis, the process of burning stored fats to generate heat. Cold exposure is a known way to activate brown adipose tissue through b3-adrenergic signaling. This signaling pathway causes an upregulation of thermogenesis in brown adipocytes and beige adipocytes, which is white adipose tissue that “browns” and becomes metabolically active. …

Innovation In Surgical Training: Simulating Prosthetic Heart Valves And Annuloplasty Rings Using Pacifiers For Cardiac Surgery Wet-Labs In A Resource Limited Setting, Sara Iqbal, Waris Ahmad

Section of Cardiothoracic Surgery

Conducting a hands-on cardiac wet-lab on valvular surgeries in a resource-limited setting is restricted by the lack of prosthetic heart valves and annuloplasty rings for developing cognitive and technical skills required to understand and protect the three-dimensional cardiac anatomy. In recent times, simulation is regarded as an effective tool in surgical education and has proven to improve the technical skills of trainees. The current short report presents a novel simulator to mimic heart valve replacement surgeries by using a pacifier as a prosthetic valve and annuloplasty ring. Considering resource-constraints in the local context, pacifier-based valve simulators can be usedful as …

Paradigm Shift In The Surgical Training: The Era Of Innovation, Simulation And Beyond, Syed Shahabuddin, Shiraz Hashmi, Yasir Khan, Shahid Ahmed Sami

Section of Cardiothoracic Surgery

This is an era of transformation of surgical education and training. Modern methods of training are being introduced at a rapid pace and are being adopted in surgical practice not only to improve the outcomes and patient satisfaction, but also to provide an opportunity to develop a new well-structured training curriculum by integrating both traditional and modern approaches to teach and learn surgical skills. Various surgical simulators are in use as training aids and are constantly undergoing further refinement and development. To achieve a smooth transition in surgical training to modern methods, a structured programme has to be developed and …

Microbiomes Of Blood-Feeding Arthropods: Genes Coding For Essential Nutrients And Relation To Vector Fitness And Pathogenic Infections. A Review, Daniel E. Sonenshine, Philip E. Stewart

Biological Sciences Faculty Publications

Blood-feeding arthropods support a diverse array of symbiotic microbes, some of which facilitate host growth and development whereas others are detrimental to vector-borne pathogens. We found a common core constituency among the microbiota of 16 different arthropod blood-sucking disease vectors, including Bacillaceae, Rickettsiaceae, Anaplasmataceae, Sphingomonadaceae, Enterobacteriaceae, Pseudomonadaceae, Moraxellaceae and Staphylococcaceae. By comparing 21 genomes of common bacterial symbionts in blood-feeding vectors versus non-blooding insects, we found that certain enteric bacteria benefit their hosts by upregulating numerous genes coding for essential nutrients. Bacteria of blood-sucking vectors expressed significantly more genes (p < 0.001) coding for these essential nutrients than those of non-blooding insects. Moreover, compared to endosymbionts, the genomes of enteric bacteria also contained significantly more genes (p < 0.001) that code for the synthesis of essential amino acids and proteins that detoxify reactive oxygen species. In contrast, microbes in non-blood-feeding insects expressed few gene families coding for these nutrient categories. We also discuss specific midgut bacteria essential for the normal development of pathogens (e.g., Leishmania) versus …

Health Systems Approach To Ensure Quality And Safety Amid Covid-19 Pandemic In Pakistan, Nousheen Pradhan, Anam Shahil Feroz, Syed Mairajuddin Shah

Community Health Sciences

Ensuring quality and safe care during the coronavirus disease 2019 (COVID-19) pandemic offers a challenge to already strained health systems in low and middle-income countries (LMICs), such as Pakistan with less shock-absorbing capacities. There is a dearth of evidence on mechanisms to provide optimum quality care to COVID-19 patients in the resource-constrained healthcare environment. The lessons learned from the Ebola virus outbreak for the deficient health systems and quality improvement are considered to propose strengthening the health systems response to deliver quality-assured care to patients during the current pandemic. In this regard, the World Health Organization (WHO) health systems framework …

Effect Of Mutation And Vaccination On Spread, Severity, And Mortality Of Covid-19 Disease, Dr Hossam Zawbaa, Hasnaa Osama, Ahmed El‐Gendy, Haitham Saeed, Hadeer S. Harb, Yasmin M. Madney, Mona Abdelrahman, Marwa Mohsen, Ahmed M.A. Ali, Mina Nicola, Marwa O. Elgendy, Ihab A. Ibrahim, Mohamed E.A. Abdelrahim

Articles

Coronavirus disease 2019 (COVID-19) has had different waves within the same country. The spread rate and severity showed different properties within the COVID-19 different waves. The present work aims to compare the spread and the severity of the different waves using the available data of confirmed COVID-19 cases and death cases. Real-data sets collected from the Johns Hopkins University Center for Systems Science were used to perform a comparative study between COVID-19 different waves in 12 countries with the highest total performed tests for severe acute respiratory syndrome coronavirus 2 detection in the world (Italy, Brazil, Japan, Germany, Spain, India, …

Sex-Related Differences In Murine Models Of Chemically Induced Pulmonary Fibrosis, Pavel Solopov, Ruben Manuel Luciano Colunga Biancatelli, Christiana Dimitropoulou, John D. Catravas

Bioelectrics Publications

We developed two models of chemically induced chronic lung injury and pulmonary fibrosis in mice (intratracheally administered hydrochloric acid (HCl) and intratracheally administered nitrogen mustard (NM)) and investigated male-female differences. Female mice exhibited higher 30-day survival and less weight loss than male mice. Thirty days after the instillation of either HCl or NM, bronchoalveolar lavage fluid displayed a persistent, mild inflammatory response, but with higher white blood cell numbers and total protein content in males vs. females. Furthermore, females exhibited less collagen deposition, milder pulmonary fibrosis, and lower Ashcroft scores. After instillation of either HCl or NM, all animals displayed …

Nitrite Supplementation Restores Aortic Health In Chronically Stressed Mice, Tyler Coblentz

Graduate Theses, Dissertations, and Problem Reports (ETD)

Chronic stress increases the risk of developing cardiovascular disease potentially via increases in elastic artery stiffness and endothelial dysfunction. Decreased bioavailability of the potent vasodilator nitric oxide (NO) describes a hallmark of endothelial dysfunction. Nitrite reduces into active NO, providing an alternative pathway of NO restoration. The effect of nitrite supplementation on aortic endothelial function has yet to be determined in chronically stressed mice. We hypothesized that nitrite supplementation would rescue chronic stress-attributed impairments in aortic endothelial function.

Mice at 18 weeks of age underwent an unpredictable chronic mild stress (UCMS; 5 days/week for 7 hrs/day) paradigm to elicit a …

Impact Of Smoking And Hpv Status On Cervical Cancer Survival In Women Living In Kentucky, 2004-2005 And 2014-2015, Brittany M. Mckinley

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

BACKGROUND/ OBJECTIVE: Cervical cancer is the fourth most commonly occurring malignancy in women worldwide, with an estimated 530,000 new cases and 270,000 new deaths each year (Small et al, 2017). While the incidence of cervical cancer has decreased by approximately 1.9% per year between 2007 and 2011, the death rate has remained stable (Bernard et al, 2014). Studies have shown that nearly all cervical cancer cases are associated with the Human Papilloma Virus (HPV). Many studies support the association of smoking with increased risk of invasive cervical cancer in women with high-risk HPV (Castle et al, 2002; Fang et al, …

Methenamine Prophylaxis For Recurrent Urinary Tract Infections In A Tertiary Referral Center, Cameron A. Wade

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

Purpose: Methenamine hippurate (MH) is a urinary antiseptic, indicated for prophylaxis of recurrent urinary tract infections (UTIs) but with only few and limited studies regarding its efficacy. To help address this knowledge gap we reviewed our experience with MH for UTI prophylaxis, focusing on women with recurrent uncomplicated UTIs.

Materials and Methods: The University of Kentucky electronic health record was queried to identify adults who were prescribed MH from the Urology clinic between January 2013 and January 2019. Charts were reviewed to assess patient-reported UTI frequency, demographics and relevant health factors. Treatment success was defined as 0-1 UTI in 6 …

Systemic Versus Local Injection Of Bone Marrow Mesenchymal Stem Cells On 5-Fluorouracil Treated Parotid Glands Of Albino Rats, Caroline Maged Massieh, Medhat El Zainy, Reham Magdy Amin, Iman Fathy

Dentistry

ABSTRACT Objective: Head and neck cancer is the sixth leading cancer by incidence worldwide and eighth by death. Recent reports revealed that, not only radiotherapy but also chemotherapy may induce xerostomia. The aim of this study was to compare the possible regenerative effect of BMSCs through systemic and local injections. Material and Methods: 52 male Albino rats were randomly divided into 4 groups: Group 1: 10 rats received 0.5 ml of PBS by injection. Group 2: 14 rats received an intraperitoneal injection of 5-FU drug. Group 3: 14 rats were injected the same dose of 5-FU then received an intraglandular …

Occupational Health Practices Among Dental Care Professionals Before And During The Covid-19 Pandemic, Sean Banaee, Denise M. Claiborne, Muge Akpinar-Elci

Community & Environmental Health Faculty Publications

BACKGROUND: The COVID-19 pandemic has posed a substantial burden on dental care professionals. While dentistry is known as one of the most exposed and high-risk professions, dental care professionals are indeed at even greater risk.

OBJECTIVE: The aim of this study was to assess knowledge, attitudes, occupational health practices, personal protective equipment usage, and mental stressors during COVID-19 pandemic among dental care professionals.

METHODS: A cross-sectional study was conducted among dental care professionals who were subscribers to a dental hygiene journal using a self-administered online survey (n = 1047 respondents). Cross-tabulations were performed to determine differences in the responses to …