Diseases Commons^™

Metabolic Alterations In Pancreatic Cancer Progression, Enza Vernucci, Jaime Abrego, Venugopal Gunda, Surendra K. Shukla, Aneesha Dasgupta, Vikrant Rai, Nina V. Chaika, Kyla Buettner, Alysha Illies, Fang Yu, Audrey J. Lazenby, Benjamin J. Swanson, Pankaj K. Singh

Journal Articles: Eppley Institute

Pancreatic cancer is the third leading cause of cancer-related deaths in the USA. Pancreatic tumors are characterized by enhanced glycolytic metabolism promoted by a hypoxic tumor microenvironment and a resultant acidic milieu. The metabolic reprogramming allows cancer cells to survive hostile microenvironments. Through the analysis of the principal metabolic pathways, we identified the specific metabolites that are altered during pancreatic cancer progression in the spontaneous progression (KPC) mouse model. Genetically engineered mice exhibited metabolic alterations during PanINs formation, even before the tumor development. To account for other cells in the tumor microenvironment and to focus on metabolic adaptations concerning tumorigenic …

Fascin Controls Metastatic Colonization And Mitochondrial Oxidative Phosphorylation By Remodeling Mitochondrial Actin Filaments, Shengchen Lin, Chongbiao Huang, Venugopal Gunda, Jianwei Sun, Srikumar P. Chellappan, Zengxun Li, Victoria Izumi, Bin Fang, John Koomen, Pankaj K. Singh, Jihui Hao, Shengyu Yang

Journal Articles: Eppley Institute

The deregulation of the actin cytoskeleton has been extensively studied in metastatic dissemination. However, the post-dissemination role of the actin cytoskeleton dysregulation is poorly understood. Here, we report that fascin, an actin-bundling protein, promotes lung cancer metastatic colonization by augmenting metabolic stress resistance and mitochondrial oxidative phosphorylation (OXPHOS). Fascin is directly recruited to mitochondria under metabolic stress to stabilize mitochondrial actin filaments (mtF-actin). Using unbiased metabolomics and proteomics approaches, we discovered that fascin-mediated mtF-actin remodeling promotes mitochondrial OXPHOS by increasing the biogenesis of respiratory Complex I. Mechanistically, fascin and mtF-actin control the homeostasis of mtDNA to promote mitochondrial OXPHOS. The …

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.

Heart To Heart: Educating Allied Healthcare Students And Professionals About Heart Failure, Samantha M. Barefoot

Occupational Therapy Doctorate Capstone Projects

Heart failure (HF) is a health problem which providing necessary education to healthcare professionals who serve individuals with HF allows for continuity of care and the promotion of disease management for this population. The intent of this research was to determine if providing an educational in-service to allied healthcare students and practitioners increased their knowledge of OT’s role with HF clients and about HF itself as a condition interfering with occupation. The design of this study involved collecting pre/post survey data to evaluate the knowledge of the participants about the HF population and gathering participant satisfaction data regarding the in-service. …

A Population-Based Analysis Of Patient Age And Other Disparities In The Treatment Of Ovarian Cancer In Central Appalachia And Kentucky, Robert Ore

Theses and Dissertations--Clinical Research Design

Objectives: Adherence to National Comprehensive Cancer Network (NCCN) guidelines for ovarian cancer treatment improves patient outcomes. The aim of this study was to assess disparities associated with ovarian cancer treatment in the state of Kentucky and central Appalachia.

Methods: Data on patients diagnosed as having ovarian cancer from 2007 through 2011 were extracted from administrative claims-linked Kentucky Cancer Registry data. NCCN compliance was defined by stage, grade, surgical procedure, and chemotherapy. Selection criteria were reviewed carefully to ensure data quality and accuracy. Descriptive analysis, logistic regression, and Cox regression analyses were performed to examine factors associated with guidelines compliance and …

White Matter Hyperintensities In Vascular Contributions To Cognitive Impairment And Dementia (Vcid): Knowledge Gaps And Opportunities, Jessica Alber, Suvarna Alladi, Hee-Joon Bae, David A. Barton, Laurel A. Beckett, Joanne M. Bell, Sara E. Berman, Geert Jan Biessels, Sandra E. Black, Isabelle Bos, Gene L. Bowman, Emanuele Brai, Adam M. Brickman, Brandy L. Callahan, Roderick A. Corriveau, Silvia Fossati, Rebecca F. Gottesman, Deborah R. Gustafson, Vladimir Hachinski, Kathleen M. Hayden, Alex M. Helman, Timothy M. Hughes, Jeremy D. Isaacs, Angela L. Jefferson, Sterling C. Johnson, Alifiya Kapasi, Silke Kern, Jay C. Kwon, Juraj Kukolja, Athene Lee, Brittani R. Price, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

White matter hyperintensities (WMHs) are frequently seen on brain magnetic resonance imaging scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMHs are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer's disease [AD]). WMHs are also seen in cognitively healthy people. In this collaboration of academic, clinical, and pharmaceutical industry perspectives, we identify outstanding questions about WMHs and their relation to cognition, dementia, and AD. What molecular and cellular changes underlie WMHs? What are the neuropathological correlates of WMHs? To what extent are demyelination and inflammation present? Is it helpful to …

Mathematical Modeling Of Type 1 Diabetes, Gianna Wu

HMC Senior Theses

Type 1 Diabetes (T1D) is an autoimmune disease where the pancreas produces little to no insulin, which is a hormone that regulates blood glucose levels. This happens because the immune system attacks (and kills) the beta cells of the pancreas, which are responsible for insulin production. Higher levels of glucose in the blood could have very negative, long term effects such as organ damage and blindness.

To date, T1D does not have a defined cause nor cure, and research for this disease is slow and difficult due to the invasive nature of T1D experimentation. Mathematical modeling provides an alternative approach …

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 …

A Meta-Analysis Of Neuromyelitis Optica Epidemiology In Latin American Nations, Brittany M. Zengotita

Honors Undergraduate Theses

Neuromyelitis Optica (NMO) is a rare, autoimmune, neurodegenerative disease selectively affecting the optic nerves and spinal cord. Relapsing NMO is nine times more prevalent in women than in men and approximately one-quarter of NMO patients have symptoms of another autoimmune disorder (National Institute of Health, 2019). NMO has not been linked to any genetic mutations and the cause of the disorder is unknown beyond the general understanding that the body produces anti-aquaporin-4 antibodies (AQP4) which mistakenly attack cells in the nervous system. NMO affects roughly one percent of that of Multiple Sclerosis (4000-8000 patients total) in the United States, but …

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.

Safety Constraint Optimization Of Combination Drug Therapy In Hypertension Clinical Trials, Victor Chukwu

College of Graduate Studies: Theses & Dissertations

In Clinical Practice, combination drug therapy has become common in treating many disease conditions. The purpose of these combinations is often to ensure optimal efficacy and to reduce adverse effects that may arise from monotherapy. Clinical trials have also been conducted to ensure efficacy and safety of these combinations before they are introduced into the market. However, adverse effects still occur with combination therapies. The objective of this study is to (1) To determine a region of optimum doses of Drug A and Drug B in combination while focusing on efficacy alone (2) To determine a region of optimum doses …

Are Chronic Inflammatory Diseases Associated With Trauma Exposure And Gender? An Empirical Analysis Of Self-Reported Trauma And Health Histories Of Men And Women, Meghan Lacienski

College of Graduate Studies: Theses & Dissertations

A growing body of research indicates an association between trauma, inflammation, and chronic inflammatory disease; however, the mechanisms of this relationship are not fully understood, and the salience of potential risk factors, such as cumulative effects of trauma, trauma type, and gender, remain unclear. Trauma is associated with poor mental and physical health, such as PTSD, depression, and chronic inflammatory conditions, and this association may be stronger when certain risk factors are considered (Brody, Pratt, & Hughes, 2018; Groer, Kane, Williams, & Duffy, 2014; Husky, Mazure, & Kovess-Masfety, 2018; Kilpatrick et al., 2013). For example, sexual trauma and multiple traumatic …

Senecavirus A: Pathogenicity And Interactions With Host Cell Death Pathway, Maureen Hoch Vieira Fernandes

Electronic Theses and Dissertations

Senecavirus A (SVA) is a positive sense single-strand RNA virus of the genus Senecavirus, family Picornaviridae. Senecavirus A is an emerging picornavirus of swine, which causes vesicular disease (VD) in pigs that is clinically indistinguishable from footand- mouth disease and other high consequence VDs of swine. There is evidence that SVA has been circulating in the US swine population since the late eighty’s, however, recently the virus emerged worldwide, and it has been associated with several VD outbreaks in pigs in many of the major swine producing countries. Despite the recent surge in the number of cases of …

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 …

Effectiveness Of Digital Media Technologybased Interventions On Hiv & Sti Risk Reduction Among Young People: A Metaanalysis, Paul Sherwin O. Tarnate, Keith Roger R. Serrano, Vanessa-Maria F. Torres-Ticzon, Kathlynne Anne A. Senen

Ateneo School of Medicine and Public Health Publications

Background: Prevention strategies delivered through digital media technology (DMT) have been developed to reduce HIV incidence among young people. However, no best-practice DMT intervention strategies exist in handling HIV prevention programs among young people. Objectives: To determine the effectiveness of DMT-based interventions in reducing risk-taking behaviours among young people that may predispose them to acquiring HIV and other sexually transmitted infections. Subjects and Selection Criteria: Randomized controlled trials and quasi-experimental studies with rigorous controls comparing DMT-based interventions and controls on reducing risk-taking behaviors among young people aged 10-24 years were included. Data Collection: Search methods were done on the following: …

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.

Conformational Flexibility In The Enterovirus Rna Replication Platform, Meghan S. Warden, Kai Cai, Gabriel Cornilescu, Jordan E. Burke, Komala Ponniah, Samuel E. Butcher, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

A presumed RNA cloverleaf (5′CL), located at the 5′-most end of the noncoding region of the enterovirus genome, is the primary established site for initiation of genomic replication. Stem–loop B (SLB) and stem–loop D (SLD), the two largest stem–loops within the 5′CL, serve as recognition sites for protein interactions that are essential for replication. Here we present the solution structure of rhinovirus serotype 14 5′CL using a combination of nuclear magnetic resonance spectroscopy and small-angle X-ray scattering. In the absence of magnesium, the structure adopts an open, somewhat extended conformation. In the presence of magnesium, the structure compacts, bringing SLB …

Waist Circumference And The Relation To Aerobic Exercise And Perception Of Illness In Adults With Type 2 Diabetes Mellitus, Bailey J. Huebner

Masters Theses

The purpose of this study was to observe the relationship between waist circumference (WC), amount of aerobic exercise performed weekly and overall Health Belief Model (HBM) score in adults with diagnosed type 2 diabetes mellitus (T2DM). Members from a local Midwest adult fitness program (n = 5) who had been diagnosed T2DM participated in this study. Participants ranged in age from 70 to 80 years with an average age of 74 years. Four of the participants were female and one participant was male. The questions included in this study were 1 .) in those with diagnosed T2DM, was a low …

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 …

Dysmenorrhea Among High-School Students And It's Associated Factors In Kuwait, Sharefah Al-Matouq, Hessah Al-Mutairi, Ohood Al-Mutairi, Fatima Abdulaziz, Dana Al-Basri, Mona Al-Enzi, Abdullah Al-Taiar

Community & Environmental Health Faculty Publications

Background

Although dysmenorrhea is not a life-threatening condition, it can cause a substantial burden on individuals and communities. There is no data on the prevalence of dysmenorrhea in Kuwait. This study aimed to estimate the prevalence of dysmenorrhea among female public high-school students in Kuwait and investigate factors associated with dysmenorrhea.

Methods

A cross-sectional study using multistage cluster sampling with probability proportional to size method was conducted on 763 twelfth grade female public high-school students (aged 16–21 years). We used face-to-face interview with a structured questionnaire to collect data on dysmenorrhea and presumed risk factors. Weight and height of the …

A 3d Bioprinter Platform For Mechanistic Analysis Of Tumoroids And Chimeric Mammary Organoids, John A. Reid, Xavier-Lewis Palmer, Peter A. Mollica, Nicole Northam, Patrick C. Sachs, Robert D. Bruno

School of Medical Diagnostics & Translational Sciences Publications

The normal mammary microenvironment can suppress tumorigenesis and redirect cancer cells to adopt a normal mammary epithelial cell fate in vivo. Understanding of this phenomenon offers great promise for novel treatment and detection strategies in cancer, but current model systems make mechanistic insights into the process difficult. We have recently described a low-cost bioprinting platform designed to be accessible for basic cell biology laboratories. Here we report the use of this system for the study of tumorigenesis and microenvironmental redirection of breast cancer cells. We show our bioprinter significantly increases tumoroid formation in 3D collagen gels and allows for precise …

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 …

The Impact On Cost, Quality, And Patient Satisfaction When Delivering Care To Acutely Ill Adults In An At-Home Care Model Versus An Inpatient Hospital Setting., Franchesca M. Adams

Honors Theses and Capstones

The impact on cost, quality, and patient satisfaction when delivering care to acutely ill adults in an at-home care model versus an inpatient hospital setting. Hospital level care for certain acute conditions can be safely delivered in the patient’s home while lowering the cost per episode of care, maintaining or improving patient experience, and improving safety and patient/care giver education as well as care coordination, at the Critical Access Hospital (CAH) level.

Myopia Outcome Study Of Atropine In Children (Mosaic): Design And Methodology, Saoirse Mccrann, Daniel Ian Flitcroft, John Butler, James Loughman

Articles

Purpose

The Myopia Outcome Study of Atropine in Children (MOSAIC) aims to explore the efficacy, safety, acceptability and mechanisms of action of 0.01% atropine for myopia control in a European population.

Methods

MOSAIC is an investigator-led, double-masked, placebo-controlled, randomised clinical trial investigating the efficacy, safety and mechanisms of action of 0.01% atropine eyedrops in myopic progression management. During phase 1 of the trial, 250 children aged 6-16 years with progressive myopia apply eye drops once nightly in both eyes from randomisation to month 24. No treatment is given during phase 2 from month 24 to 36 (washout period) for those …

Journey With Autism: Successful Educational And Social Interventions From A Single Case Study, Kwame M. De Jonge-Moore

Dissertations

Problem

Statistics indicate that Autism Spectrum Disorder (ASD) is on the increase in America and worldwide (Xu, Strathearn, Liu, & Bao, 2018; Baio et al., 2018). Autism spectrum disorder can impair an individual’s ability to engage in neurotypical behavior, which has the potential to increase their vulnerability to being shunned and bullied. This makes autism a major societal concern with significant costs to the individual, their family, private/public health insurance, state financial aid programs, and to the nation. This present study was undertaken to determine, in the opinions of those connected to the case, whether the interventions engaged in this …

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 …