Diseases Commons^™

Inhibition Of Geranylgeranyl Diphosphate Synthase Is A Novel Therapeutic Strategy For Pancreatic Ductal Adenocarcinoma, Staci L. Haney, Michelle L. Varney, Yashpal S. Chhonker, Simon Shin, Kamiya Mehla, Ayrianne J. Crawford, Heather Jensen Smith, Lynette M. Smith, Daryl J. Murry, Michael A. Hollingsworth, Sarah A. Holstein

Journal Articles: Eppley Institute

Rab proteins play an essential role in regulating intracellular membrane trafficking processes. Rab activity is dependent upon geranylgeranylation, a post-translational modification that involves the addition of 20-carbon isoprenoid chains via the enzyme geranylgeranyl transferase (GGTase) II. We have focused on the development of inhibitors against geranylgeranyl diphosphate synthase (GGDPS), which generates the isoprenoid donor (GGPP), as anti-Rab agents. Pancreatic ductal adenocarcinoma (PDAC) is characterized by abnormal mucin production and these mucins play important roles in tumor development, metastasis and chemo-resistance. We hypothesized that GGDPS inhibitor (GGDPSi) treatment would induce PDAC cell death by disrupting mucin trafficking, thereby inducing the unfolded …

Utility Of Point-Of-Care Beta-Hydroxybutyrate Testing For Predicting Diabetic Ketoacidosis In The Pediatric Emergency Department, Michelle Knoll, Kelsee Halpin, Ryan Mcdonough

Posters

The objective of our investigation was to describe the diagnostic characteristics of point-of-care capillary beta-hydroxybutyrate (BOHB) testing to predict diabetic ketoacidosis among pediatric patients presenting with hyperglycemia in the pediatric emergency department.

Selective Inhibition Of Histone Deacetylases 1/2/6 In Combination With Gemcitabine: A Promising Combination For Pancreatic Cancer Therapy, Richard S. Laschanzky, Lisa E. Humphrey, Jihyun Ma, Lynette M. Smith, Thomas J. Enke, Surendra K. Shukla, Aneesha Dasgupta, Pankaj K. Singh, Gillian M. Howell, Michael G. Brattain, Quan P. Ly, Adrian R. Black, Jennifer D. Black

Journal Articles: Eppley Institute

Pancreatic ductal adenocarcinoma (PDAC) has a five-year survival rate of <10% due in part to a lack of effective therapies. Pan-histone deacetylase (HDAC) inhibitors have shown preclinical efficacy against PDAC but have failed in the clinic due to toxicity. Selective HDAC inhibitors may reduce toxicity while retaining therapeutic efficacy. However, their use requires identification of the specific HDACs that mediate the therapeutic effects of HDAC inhibitors in PDAC. We determined that the HDAC1/2/3 inhibitor Mocetinostat synergizes with the HDAC4/5/6 inhibitor LMK-235 in a panel of PDAC cell lines. Furthermore, while neither drug alone synergizes with gemcitabine, the combination of Mocetinostat, LMK-235, and gemcitabine showed strong synergy. Using small interfering (si)RNA-mediated knockdown, this synergy was attributed to inhibition of HDACs 1, 2, and 6. Pharmacological inhibition of HDACs 1 and 2 with Romidepsin and HDAC6 with ACY-1215 also potently synergized with gemcitabine in a panel of PDAC cell lines, and this drug combination potentiated the antitumor effects of gemcitabine against PDAC xenografts in vivo. Collectively, our data show that inhibition of multiple HDACs is required for therapeutic effects of HDAC inhibitors and support the development of novel strategies to inhibit HDACs 1, 2, and 6 for PDAC therapy.

Human Islet Response To Selected Type 1 Diabetes-Associated Bacteria: A Transcriptome-Based Study, Ahmed M. Abdellatif, Heather Jensen Smith, Robert Z. Harms, Nora Sarvetnick

Journal Articles: Eppley Institute

Type 1 diabetes (T1D) is a chronic autoimmune disease that results from destruction of pancreatic β-cells. T1D subjects were recently shown to harbor distinct intestinal microbiome profiles. Based on these findings, the role of gut bacteria in T1D is being intensively investigated. The mechanism connecting intestinal microbial homeostasis with the development of T1D is unknown. Specific gut bacteria such as Bacteroides dorei (BD) and Ruminococcus gnavus (RG) show markedly increased abundance prior to the development of autoimmunity. One hypothesis is that these bacteria might traverse the damaged gut barrier, and their constituents elicit a response from human islets that causes …

Global Health Experience In Botswana, Sarah Bieser

Posters

Describes experience providing care at the Botswana-Baylor Children's Center of Excellence in Gabarone, Botswana and the Princess Marina Hospital.

Epidemiology, Clinical Features And Outcomes Of Patients With Sickle Cell Disease Hospitalized With Influenza, Kyle P. Openo

College of Graduate Studies: Theses & Dissertations

Influenza is a respiratory viral infection responsible for annual epidemics, periodic pandemics and regularly causes substantial morbidity, mortality and economic burden worldwide. In the United States alone, influenza causes between 9.2 – 35.6 million cases, 140,000 to 710,000 hospitalizations and 12,000 – 56,000 deaths annually. Individuals with comorbid health conditions are at increased risk of hospitalization and severe outcomes from influenza infection and were recommended for vaccination prior to universal vaccine recommendations. Individuals with sickle cell disease (SCD) have been included in this group for decades though limited data existed to describe influenza among those with SCD. Recent studies showed …

Inhibition Of Cancer Stem Cells By Glycosaminoglycan Mimetics, Connor P. O'Hara

Theses and Dissertations

Connor O’Hara July 29, 2019

Inhibition of Cancer Stem Cells by Glycosaminoglycan Mimetics

In the United States cancer is the second leading cause of death, with colorectal cancer (CRC) being the third deadliest cancer and expected to cause over 51,000 fatalities in 2019 alone.¹ The current standard of care for CRC depends largely on the staging, location, and presence of metastasis.² As the tumor grows and invades nearby lymph tissue and blood vessels, CRC has the opportunity to invade not only nearby tissue but also metastasize into the liver and lung (most commonly).³ The 5-year survival rate …

Incidence And Predictor Variables Of Pressure Injuries In Patients Undergoing Ventricular Assist Device And Total Artificial Heart Surgeries: An Eight-Year Retrospective Review, Christopher T. Brindle

Theses and Dissertations

BACKGROUND

Cardiac surgery patients have some of the highest reported incidence and prevalence of pressure injuries (PI). A growing subset of cardiac surgery include patients with end-stage heart failure who undergo ventricular assist device (VAD) or total artificial heart (TAH) surgery. The risk of PI and their natural history of development in this population are unknown and the specific risk factors for PI development remain unexplored.

OBJECTIVES

To perform a systematic review of the literature to identify the incidence and risk factors of PI development in patients undergoing VAD-TAH surgery and thereby inform study design and variables in an eight-year …

Recent Advances In The Vibrational Spectroscopic Diagnosis Of Non-Small Cell Lung Cancer, Declan O'Dea, Fiona Lyng, Siobhan Nicholson, Finbar O'Connell, Aoife Maguire, Alison Malkin

Articles

Lung cancer is the leading cause of cancer deaths worldwide accounting for 1.69 million deaths in 2015. Studies have indicated a 5 year survival rate of 8%–15% in western countries, although a survival rate as low as 1% has been demonstrated for late stage diagnosis. With the advent of targeted therapies, it is imperative to accurately differentiate non-small cell lung cancer (NSCLC) subtypes in order to ensure efficacy of treatment for patients. Immunohistochemistry and molecular techniques for the diagnosis of NSCLC are increasingly part of the diagnostic algorithm and clinical work-up of lung cancer patients, however due to the limitation …

Early Aggressive Insulin Therapy In Type 2 Diabetes, Bryan Johnson

Physician Assistant Scholarly Project Posters

Metformin has been proven beneficial for the first-line treatment of type 2 diabetic mellitus (T2DM) due to its efficacy and low adverse effect profile. Current US guidelines do not address the use of early intensive insulin use in T2DM. Treatment plans are slowly adjusted over the months until the A1C goal is met. Insulin is initiated several years after the time of T2DM diagnosis and utilized as second-line therapy. Dual therapy of insulin and metformin have shown regression of T2DM in certain patient populations. However, the linear relationship between diabetes and cardiovascular disease does not show greater improvement with dual …

Platelets To The Rescue? A Literature Review Of The Safety And Efficacy Of Platelet-Rich Plasma For Symptomatic Osteoarthritis Of The Knee, Timothy Simonich

Physician Assistant Scholarly Project Posters

Osteoarthritis of the knee is one of the most common joint disorders in the United States with rising prevalence due to obesity and an aging population. Regarding non-surgical approaches to management, there has been growing interest in the use of intra-articular injections with Platelet Rich Plasma (PRP).

Delaying Diabetes In The Native American Population, Seth Tramm

Physician Assistant Scholarly Project Posters

Diabetes is a debilitating disease process caused by the body’s inability to control blood glucose levels. With over 30 million diabetics in the United States and another 85 million prediabetics, the effects of this disease are wide-spread and far-reaching. Native American/Alaska Native populations have a nearly two-fold increase in prevalence of diabetes when compared to non-native populations. Risk factors for diabetes in all populations include modifiable risks such as obesity, diet, and physical inactivity as well as non-modifiable factors such as age, family history, and ethnicity. Studies have shown that early identification of symptoms, coupled with proper and intentional treatment …

Benefits Of 3d Breast Tomosynthesis Combined With 2d Digital Mammography In Screening Women For Breast Cancer, Danielle M. Swanson

Physician Assistant Scholarly Project Posters

• Breast cancer screening imaging options have progressed greatly over • the years in sensitivity, specificity, and image quality. According to DynaMed Plus, in 2012 there were 522,000 deaths by breast cancer and 1,677,000 total cases of breast cancer documented (Dynamed, 2018). For years, traditional screening for breast cancer involved 2D digital mammography which obtains two views of each breast. With advances in technology, the use of 3D breast tomosynthesis has become an advantageous addition to routine breast cancer screening protocols at many health care facilities.

• My literature review of articles was found in PubMed, DynaMed Plus, Cochrane Library, …

Therapeutic Targeting Of Relaxin Signaling In Ischemic Heart Disease, Siva Teja Vk Devarakonda

Theses and Dissertations

Ischemic heart disease is characterized by reduced perfusion of oxygenated blood to the myocardium, potentially resulting in infarction upon occlusion of coronary arteries. While prompt reperfusion and advances in in-hospital care have led to a decline in short term mortality, sustained damage to the ventricle, along with reperfusion injury, can lead to progressive deterioration in cardiac function. Limiting the extent of this initial ischemia-reperfusion injury and combating the course of adverse remodeling remains the scope of several preclinical studies geared towards improving cardiac health after MI. To this, relaxin-2 – the peptide hormone that regulates maternal hemodynamic function during pregnancy …

Prospective Observational Study In Patients With Obstructive Lung Disease: Novelty Design, Helen K. Reddel, Maria Gerhardsson De Verdier, Alvar Agustí, Gary Anderson, Richard Beasley, Elisabeth H. Bel, Christer Janson, Barry Make, Richard J. Martin, Ian Pavord, David Price, Christina Keen, Asparuh Gardev, Stephen I. Rennard, Alecka Sveréus, Aruna T. Bansal, Lance Brannman, Niklas Karlsson, Javier Nuevo, Fredrik Nyberg, Simon S. Young, Jørgen Vestbo

Journal Articles: Pulmonary & Critical Care Med

Asthma and chronic obstructive pulmonary disease (COPD) have overlapping clinical features and share pathobiological mechanisms but are often considered distinct disorders. Prospective, observational studies across asthma, COPD and asthma-COPD overlap are limited. NOVELTY is a global, prospective observational 3-year study enrolling ∼12 000 patients ≥12 years of age from primary and specialist clinical practices in 19 countries (ClinicalTrials.gov identifier: NCT02760329). NOVELTY's primary objectives are to describe patient characteristics, treatment patterns and disease burden over time, and to identify phenotypes and molecular endotypes associated with differential outcomes over time in patients with a diagnosis/suspected diagnosis of asthma and/or COPD. NOVELTY …

Comparative Assessment Of Methicillin Resistant Staphylococcus Aureus Diagnostic Assays For Use In Resource-Limited Settings, A. Ayebare, Lisa M. Bebell, Joel Bazira, S. Ttendo, V. Katawera, David Bangsberg, Mark J. Siedner, Multiple Additional Authors

OHSU-PSU School of Public Health Faculty Publications and Presentations

Background: The rise of methicillin-resistant Staphylococcus aureus(MRSA) is a global health concern. Paucity of data on MRSA carriage prevalence and diagnostic methods in resource-limited settings hampers efforts to define the problem and plan an appropriate response. Additionally, high variability in cost and logistical characteristics of MRSA screening methods may impede infection control efforts. We compared the performance of locally-available chromogenic agar BD CHROMagar MRSA II and two PCR-based assays (Hain GenoQuick MRSA and Cepheid Xpert SA Complete) for the detection of asymptomatic MRSA carriage in nasal swabs.

Results: During 2015, we enrolled 500 patients from five hospital …

Improving Access To Clean Water In Rural Ecuador: The Connection Between Willingness To Pay And Population Health, Micalea Leaska

Capstone Collection

Climate change is affecting social and environmental determinants of health through access to safe drinking water, safely managed sanitation systems, and access to health care services and the ability for individuals to break free from unsuitable circumstances. Ecological disturbances such as those caused by climate change can cause a shift in host vectors or a change in habitat that results in a greater likelihood of the pathogen coming in contact with humans. Water, sanitation, and hygiene (WASH) services and their accessibility to populations can directly impact a community’s vulnerability to diseases and limiting factors to increase economic growth. If rural …

Autologous Peripheral Nerve Grafts To The Brain For The Treatment Of Parkinson's Disease, Andrew Welleford

Theses and Dissertations--Neuroscience

Parkinson’s disease (PD) is a disorder of the nervous system that causes problems with movement (motor symptoms) as well as other problems such as mood disorders, cognitive changes, sleep disorders, constipation, pain, and other non-motor symptoms. The severity of PD symptoms worsens over time as the disease progresses, and while there are treatments for the motor and some non-motor symptoms there is no known cure for PD. Thus there is a high demand for therapies to slow the progressive neurodegeneration observed in PD. Two clinical trials at the University of Kentucky College of Medicine (NCT02369003, NCT01833364) are currently underway that …

Understanding The Contributions Of Alzheimer’S Disease & Cardiovascular Risks To Cerebral Small Vessel Disease Manifest As White Matter Hyperintensities On Magnetic Resonance Imaging (Mri), Omar M. Al-Janabi

Theses and Dissertations--Clinical and Translational Science

Introduction: Alzheimer’s Diseases (AD) & cerebral small vessel disease associated with cardiovascular risk factors (cSVD) frequently coexist, differentially affecting both imaging and clinical features associated with aging and dementia. We hypothesized that Magnetic Resonance Imaging (MRI) can be used in novel ways to identify relative contributions of AD & cardiovascular risks to cSVD and brain atrophy, generating new biomarkers & insights into mixed disease states associated with cognitive decline and dementia.

Methods: Three experiments were conducted to address the overarching hypothesis. First, we visually rated the clinical MRI of 325 participants from a community-based cross-sectional sample to elucidate the relative …

Changes In Muscle Size, Quality And Power Are Related To Physical Function In Patients With Critical Illness, Kirby Mayer

Theses and Dissertations--Rehabilitation Sciences

Patients admitted to intensive care unit (ICU) are known to develop significant impairments in physical function. Patients with critical illness suffer up to 30% reductions in muscle size within the first ten days of admission to the ICU. Muscle strength testing, Medical Research Council-sum score, is current gold-standard to diagnosis ICU-acquired weakness and predicts risk of mortality and long-term physical function. Muscle power different from muscle strength in that it accounts for velocity of movement, is potentially a better independent predictor of function that has not been studied in this population. In addition, we hypothesize that muscle size and quality …

Effect Of Neoadjuvant Chemoradiation On Preoperative Pulmonary Physiology, Postoperative Respiratory Complications And Quality Of Life In Patients With Oesophageal Cancer, J. A. Elliott, L. O'Byrne, G. Foley, C. F. Murphy, Suzanne Doyle, S. King, E. M. Guinan, N. Ravi, V. Reynolds

Articles

Background: It remains controversial whether neoadjuvant chemoradiation (nCRT) for oesophageal cancer influences operative morbidity, in particular pulmonary, and quality of life. This study combined clinical outcome data with systematic evaluation of pulmonary physiology to determine the impact of nCRT on pulmonary physiology and clinical outcomes in locally advanced oesophageal cancer.

Methods: Consecutive patients treated between 2010 and 2016 were included. Three-dimensional conformal radiation was standard, with a lung dose–volume histogram of V20 less than 25 per cent, and total radiation between 40 and 41⋅4Gy. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and diffusion capacity …

A Time-Friendly, Feasible Measure Of Nutrition Knowledge In Type 1 Diabetes: The Electronic Nutrition And Carbohydrate Counting Quiz (Encq)., Arwen M. Marker, Amy E. Noser, Nicole Knecht, Mark A. Clements, Susana R. Patton

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Greater knowledge about nutrition and carbohydrate counting are associated with improved glycemic control and quality of life in youth with type 1 diabetes (T1D). However, limited assessments of nutrition and carbohydrate knowledge have been developed, and existing measures can be time-consuming, overly broad, or not conducive to routine clinical use. To fill this gap, we developed and examined the feasibility of administering the electronic Nutrition and Carbohydrate Counting Quiz (eNCQ).

METHOD: Ninety-two caregivers and 70 youth with T1D (mean age 12.5 years; mean time since diagnosis 5 years; English speaking) completed the 19-item eNCQ via tablet during a routine …

Insulin Pump Adherence Behaviors Do Not Correlate With Glycemic Variability Among Youth With Type 1 Diabetes (T1d)., Emily Paprocki, Vincent S. Staggs, Susan Patton, Mark A. Clements

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

The Copy Number Variation Landscape Of Congenital Anomalies Of The Kidney And Urinary Tract., Miguel Verbitsky, Rik Westland, Alejandra Perez, Krzysztof Kiryluk, Qingxue Liu, Priya Krithivasan, Adele Mitrotti, David A. Fasel, Ekaterina Batourina, Matthew G. Sampson, Monica Bodria, Max Werth, Charlly Kao, Jeremiah Martino, Valentina P. Capone, Asaf Vivante, Shirlee Shril, Byum Hee Kil, Maddalena Marasà, Jun Y. Zhang, Young-Ji Na, Tze Y. Lim, Dina Ahram, Patricia L. Weng, Erin L. Heinzen, Alba Carrea, Giorgio Piaggio, Loreto Gesualdo, Valeria Manca, Giuseppe Masnata, Maddalena Gigante, Daniele Cusi, Claudia Izzi, Francesco Scolari, Joanna A E Van Wijk, Marijan Saraga, Domenico Santoro, Giovanni Conti, Pasquale Zamboli, Hope White, Dorota Drozdz, Katarzyna Zachwieja, Monika Miklaszewska, Marcin Tkaczyk, Daria Tomczyk, Anna Krakowska, Przemyslaw Sikora, Tomasz Jarmoliński, Maria K. Borszewska-Kornacka, Robert Pawluch, Maria Szczepanska, Piotr Adamczyk, Malgorzata Mizerska-Wasiak, Grazyna Krzemien, Agnieszka Szmigielska, Marcin Zaniew, Mark G. Dobson, John M. Darlow, Prem Puri, David E. Barton, Susan L. Furth, Bradley A. Warady, Zoran Gucev, Vladimir J. Lozanovski, Velibor Tasic, Isabella Pisani, Landino Allegri, Lida M. Rodas, Josep M. Campistol, Cécile Jeanpierre, Shumyle Alam, Pasquale Casale, Craig S. Wong, Fangming Lin, Débora M. Miranda, Eduardo A. Oliveira, Ana Cristina Simões-E-Silva, Jonathan M. Barasch, Brynn Levy, Nan Wu, Friedhelm Hildebrandt, Gian Marco Ghiggeri, Anna Latos-Bielenska, Anna Materna-Kiryluk, Feng Zhang, Hakon Hakonarson, Virginia E. Papaioannou, Cathy L. Mendelsohn, Ali G. Gharavi, Simone Sanna-Cherchi

Manuscripts, Articles, Book Chapters and Other Papers

Congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of pediatric kidney failure. We performed a genome-wide analysis of copy number variants (CNVs) in 2,824 cases and 21,498 controls. Affected individuals carried a significant burden of rare exonic (that is, affecting coding regions) CNVs and were enriched for known genomic disorders (GD). Kidney anomaly (KA) cases were most enriched for exonic CNVs, encompassing GD-CNVs and novel deletions; obstructive uropathy (OU) had a lower CNV burden and an intermediate prevalence of GD-CNVs; and vesicoureteral reflux (VUR) had the fewest GD-CNVs but was enriched for novel exonic CNVs, …

Analgesia And Sedation Medication Use In Infants With Congenital Diaphragmatic Hernia Is Associated With Adverse Outcome, Mark Weems, Theresa Grover, Robert Digeronimo, Jason Gien, Ruth Seabrook, Sarah Keene, Natalie Rintoul, Beverly Brozanski, John Daniel, Rachel Chapman, Burhan Mahmood, Yvette Johnson, Yigit Guner, Holly Hedrick, Isabella Zaniletti, Karna Murthy

Posters

This study describes the use and variation of sedation and analgesic medications as well as short-term clinical outcomes in infants with congenital diaphragmatic hernia.

Determining The Instructional Effectiveness Of An Online Resident Vaccine Curriculum, S. Elizabeth Williams, Shannon Clark, Barbara A. Pahud, Sharon Humiston, Donald Middleton, Kadriye O. Lewis

Posters

We developed four online modules through the Collaboration for Vaccine Education and Research (CoVER) project. The objective of this qualitative study is to determine the instructional effectiveness of the CoVER curriculum from the perspectives of medical residents.

Current Assessment And Intervention Strategies For Childhood Obesity Used By Pediatric Care Providers, Jennifer Bivins

DNP Projects

Childhood obesity rates in the United States have tripled since the 1970s in the U.S. (CDC, 2018). Due to the persistent rise in obesity rate sin children and the possible health risks associated with obesity, it is important for pediatric providers to appropriately assess and treat childhood obesity. There is limited data on what pediatric providers in the primary care setting are doing to address this growing health problem. PURPOSE: The purpose of this study was to determine current assessment and intervention strategies for childhood obesity used by pediatric health care providers at the University of Kentucky, General Pediatric clinic. …

The Effect Of Provider Education On Copd Screening Rates In The Primary Care Setting, Kelli Craig

DNP Projects

BACKGROUND: Chronic Obstructive Pulmonary Disease is one of the leading causes of morbidity and mortality in the United States. With early detection, COPD is a treatable disease, highlighting the need for an effective screening measure. The COPD Population Screener Questionnaire (COPD-PS) is a valid, accurate questionnaire that can identify individuals likely to have COPD.

PURPOSE: The purpose of this study was to evaluate the impact of a provider-based educational intervention on the knowledge, attitudes, self-efficacy and screening rates of COPD using the COPD-PS screening tool among primary care providers.

METHODS: This study was a single-center, pre/post implementation study to evaluate …

Successful Brace Treatment Of Pectus Carinatum In Osteogenesis Imperfecta Using The Dynamic Compression System., Beth A. Orrick, Amy L. Pierce, Charles L. Snyder, Uri S. Alon

Manuscripts, Articles, Book Chapters and Other Papers

Osteogenesis imperfecta (OI) is a genetic disorder of collagen resulting in a "fragile" skeleton with increased fracture risk and other complications, dependent on the specific variant. Pectus deformities of the chest wall, while not common, can be associated with OI. The use of a pectus carinatum brace in a patient with OI poses unknown risks for fractures and adverse treatment outcomes. We successfully applied external compression bracing using the dynamic compression system to one such patient. This case illustrates the ability to treat an OI patient with pectus carinatum using a nonsurgical brace, without complications, resulting in an excellent cosmetic …

Addressing Stroke Patient And Family Reasons For Not Calling 911, Maygret Ramirez, Rodney Bedgio, Virginia Ramos, Ivis Gonzalez, Yaima Miro Gonzalez, Amy Starosciak, Daniel D'Amour, Jayme Strauss, Felipe De Los Rios La Rosa

All Publications

No abstract provided.