Medicine and Health Sciences Commons^™

Integrative Cancer Immunogenomic Analysis Of Serial Melanoma Biopsies Reveals Correlates Of Response And Resistance To Sequential Ctla-4 And Pd-1 Blockade Treatment, Whijae Roh

Dissertations and Theses (Open Access)

Melanoma is the most malignant form of skin cancer. The five-year survival rate for metastatic melanoma is 19.9%. Although targeted therapy of BRAF and MEK inhibitors were developed for melanoma, resistance to therapy is inevitable. Immune checkpoint blockade, which reverses the suppression of the immune system, on the other hand, has shown a durable response in 20-30% of patients with metastatic melanoma. However, more predictive and robust biomarkers of response to this therapy are still needed, and resistance mechanisms remain incompletely understood. To address this, we examined a cohort of metastatic melanoma patients treated with sequential checkpoint blockade against cytotoxic …

Dynamic Assessment Of Nk Cell Interactions With Pediatric Tumor Cells To Predict Response To Immunotherapy, Arianexys Aquino Lopez

Dissertations and Theses (Open Access)

Due to Natural Killer (NK) cells’ capacity to target tumor cells without prior sensitization, adoptive NK cell therapy represents a promising immunotherapy approach for pediatric cancer patients. Our laboratory has developed an NK cell expansion protocol that generates large quantities of NK cells for therapeutic infusion. Given that NK cells are heterogeneous, with variable receptor expression and potential to target tumor cells, the purpose of my study was to determine whether subpopulations of NK cells with enhanced anti-tumor potential could be identified for increased potency of the NK cell infusion product. In addition, we previously showed that our expanded NK …

Role Of Cannabinoid Receptor Type 2 (Cb2) In Late Stage Atherosclerosis, Makenzie Fulmer

Electronic Theses and Dissertations

Atherosclerosis is a chronic inflammatory disorder of medium and large vessels. Immune signaling and dyslipidemia are two of several processes which influence lesion development in atherosclerosis. Cannabinoids, such as those found in marijuana, exert their effects through two cannabinoid receptors, CB1 and CB2. Recent studies using CB2 knockout mice and CB2-selective ligands have shed light on a protective role of CB2 in early stages of atherosclerosis. However, the role of CB2 in advanced stages of atherosclerosis remains unclear. To determine if CB2 plays a role in advanced atherosclerotic lesion composition and progression, we investigated the effects of systemic CB2 gene …

Oligodendrocyte Rasg12v Expressed In Its Endogenous Locus Disrupts Myelin Structure Through Increased Mapk, Nitric Oxide, And Notch Signaling, Haley E. Titus, Alejandro Lopez-Juarez, Sadiq H. Silbak, Tilat A. Rizvi, Madeleine Bogard, Nancy Ratner

Health & Biomedical Sciences Faculty Publications

Costello syndrome (CS) is a gain of function Rasopathy caused by heterozygous activating mutations in the HRAS gene. Patients show brain dysfunction that can include abnormal brain white matter. Transgenic activation of HRas in the entire mouse oligodendrocyte lineage resulted in myelin defects and behavioral abnormalities, suggesting roles for disrupted myelin in CS brain dysfunction. Here we studied a mouse model in which the endogenous HRas gene is conditionally replaced by mutant HRasG12V in mature oligodendrocytes, to separate effects in mature myelinating cells from developmental events. Increased myelin thickness due to decompaction was detectable within one month of HRasG12V expression …

Developing Algorithms For Quantifying The Super Resolution Microscopic Data: Applications To The Quantification Of Protein-Reorganization In Bacteria Responding To Treatment By Silver Ions, Sai Divya Challapalli

Graduate Theses and Dissertations

Histone-like nucleoid structuring proteins (HNS) play significant roles in shaping the chromosomal DNA, regulation of transcriptional networks in microbes, as well as bacterial responses to environmental changes such as temperature fluctuations. In this work, the intracellular organization of HNS proteins in E. coli bacteria was investigated utilizing super-resolution fluorescence microscopy, which surpasses conventional microscopy by 10–20 fold in spatial resolution. More importantly, the changes of the spatial distribution of HNS proteins in E. coli, by addition of silver ions into the growth medium were explored. To quantify the spatial distribution of HNS in bacteria and its changes, an automatic method …

Serum Microrna-27b As A Screening Biomarker For Left Ventricular Hypertrophy, Yan Wang, Shuyan Chen, Yanhong Gao, Song Zhang

The Texas Heart Institute Journal

MicroRNA-27b (miR-27b) is frequently upregulated in pressure-overloaded hypertrophic hearts. The clinical implications of aberrant circulating miR-27b in the diagnosis and management of left ventricular hypertrophy warrant study. We investigated whether serum miR-27b is a biomarker for left ventricular hypertrophy (LVH).

We used stem-loop reverse-transcription quantitative polymerase chain reaction techniques to analyze serum miR-27b levels in 200 hypertensive patients with LVH, 100 hypertensive patients without LVH, and 100 healthy volunteers. We found that serum miR-27b levels were significantly higher in the hypertensive patients with LVH than in the hypertensive patients without LVH and in the healthy volunteers. Upon receiver operating characteristic …

Multimodal Imaging Of Anomalous Left Coronary Artery From The Pulmonary Artery In A 75-Year-Old Woman, Margaret M Fuchs, Rachel J Le, Michael W Cullen, Joseph J Maleszewski, Naser M Ammash

The Texas Heart Institute Journal

Anomalous origin of the left coronary artery from the pulmonary artery is rare and typically results in mitral regurgitation, ventricular arrhythmias, heart failure, and sudden death. The condition most often manifests itself in early childhood, but some individuals are diagnosed much later. We describe the case of a 75-year-old woman with heart failure in whom stepwise multimodal imaging revealed anomalous origin of the left coronary artery from the pulmonary artery.

Recurrent Biatrial Myxoma In A 41-Year-Old Woman After Left Atrial Myxoma Resection, Xiaoming Jia, Anjali Kohli, Jane Jarjour, Chung-Jiah Justin Chen, Brendan Gilmore, Rashed Tabbaa, Edward Lee Poythress

The Texas Heart Institute Journal

Bilateral recurrence of atrial myxoma has been reported only a few times. We describe the case of a 41-year-old woman who had undergone left atrial myxoma resection and presented 9 years later with myxomas in both atria. The patient underwent successful resection of both masses with resolution of symptoms. We discuss the phenomenon of recurrent biatrial myxoma.

A Blueprint For Life And Love, Marilyn Todd

The Texas Heart Institute Journal

No abstract provided.

Bioresorbable Scaffolds In Spontaneous Coronary Artery Dissection: Long-Term Follow-Up In 4 Patients, Santiago Jesús Camacho Freire, Antonio Enrique Gómez Menchero, Jessica Roa Garrido, Javier León Jiménez, Rosa Cardenal Piris, José Francisco Díaz Fernández

The Texas Heart Institute Journal

Spontaneous coronary artery dissection is a rare condition, and diagnosis and treatment are challenging among patients who present with acute coronary syndrome. Typically, the condition affects young females who have no underlying atherosclerotic disease. To date, few cases of bioresorbable scaffold implantation for the treatment of spontaneous coronary artery dissection have been reported. Therefore, we describe the cases of 4 patients whom we treated with scaffolds. We evaluated the long-term results by using intravascular ultrasound and optical coherence tomographic scanning.

Transition From Pre-Diabetes To Diabetes And Predictors Of Risk In Mexican-Americans, Shenghui Wu, Joseph B. Mccormick, Joanne E. Curran, Susan P. Fisher-Hoch

School of Medicine Publications

Background: No studies have examined risk factors for the transition from pre-diabetes to diabetes in populations with widespread obesity and diabetes. We determined proximal changes and factors affecting the transition among Mexican-Americans with pre-diabetes.

Methods: Participants with pre-diabetes (n=285) were recruited from our randomly sampled population-based Cameron County Hispanic Cohort. These participants were followed for an average of 27 months with repeat examination every 3 to 4 months. Metabolic health was defined as having less than 2 metabolic abnormalities (e.g., hypertension, elevated low-density lipoprotein, etc). Diabetes was identified as fasting blood glucose ≥126 mg/dL, glycated hemoglobin ≥6.5% and/or on hypoglycemic …

Trak2, A Novel Regulator Of Abca1 Expression, Cholesterol Efflux And Hdl Biogenesis, Nicole J. Lake, Rachael L. Taylor, Hugh Trahair, K. N. Harikrishnan, Joanne E. Curran, Marcio Almeida, Hemant Kulkarni, Matthew P. Johnson, Thomas D. Dyer, Michael Mahaney, Harald H. H. Goring, John Blangero

School of Medicine Publications

Aims: The recent failures of HDL-raising therapies have underscored our incomplete understanding of HDL biology. Therefore there is an urgent need to comprehensively investigate HDL metabolism to enable the development of effective HDL-centric therapies. To identify novel regulators of HDL metabolism, we performed a joint analysis of human genetic, transcriptomic, and plasma HDL-cholesterol (HDL-C) concentration data and identified a novel association between trafficking protein, kinesin binding 2 (TRAK2) and HDL-C concentration. Here we characterize the molecular basis of the novel association between TRAK2 and HDL-cholesterol concentration.

Methods and results: Analysis of lymphocyte transcriptomic data together with plasma HDL from the …

Effect Of Src Kinase Inhibition On Cytochrome C, Smac/Diablo And Apoptosis Inducing Factor (Aif) Following Cerebral Hypoxia-Ischemia In Newborn Piglets., Panagiotis Kratimenos, Ioannis Koutroulis, Beamon Agarwal, Stamatios Theocharis, Maria Delivoria-Papadopoulos

Pediatrics Faculty Publications

We have previously shown that cerebral Hypoxia-ischemia (HI) results in activation of Src kinase in the newborn piglet brain. We investigated the regulatory mechanism by which the pre-apoptotic proteins translocate from mitochondria to the cytosol during HI through the Src kinase. Newborn piglets were divided into 3 groups (n = 5/group): normoxic (Nx), HI and HI pre-treated with Src kinase inhibitor PP2 (PP2 + HI). Brain tissue HI was verified by neuropathological analysis and by Adenosine Triphosphate (ATP) and Phosphocreatine (PCr) levels. We used western blots, immunohistochemistry, H&E and biochemical enzyme assays to determine the role of Src kinase on …

Activation Des Éosinophiles Humains Par Des Nanoparticules, Denis Girard, Maxime Marion-Murphy

Rapports de recherche scientifique

L’économie du Canada, comme celle de bien d’autres pays industrialisés, bénéficie du développement des nanotechnologies dont le fort potentiel peut être exploité dans plusieurs secteurs industriels. Un nombre croissant d’entreprises québécoises de production de nanoparticules (NP) est d’ailleurs déjà implanté et tout porte à croire que d’autres emboîteront le pas dans les années à venir. Ce faisant, non seulement le nombre de travailleurs œuvrant dans la fabrication et la synthèse des NP augmentera sensiblement, mais également le nombre de ceux qui seront appelés à en manipuler et à en transformer dans les domaines des nanotechnologies en général. Une des conséquences …

Dermatomyositis, Sandi Watts

ASA Multidisciplinary Research Symposium

Dermatomyositis is a rare disease which affects the skin and muscles. This disease can manifest in children or not present until one is older. Since this disease is so rare, most individuals who are diagnosed with it will have a team of physicians who work together to help treat the patient.

Pneumonia Vaccines: Current Recommendations And Advocacy Opportunities, Laressa Bethishou

Pharmacy Faculty Articles and Research

"Despite the demonstrated efficacy of these vaccines, only 66.9% of adults over age 65 years have ever received a pneumonia vaccine. Given the consequences of acquiring pneumonia, there is both a need and an opportunity to improve vaccination rates. The pharmacist can play a valuable role in identifying high-risk patients, providing education on benefits and risks, and advocating for pneumonia vaccination when indicated."

A Low Carbohydrate, Ketogenic Diet For Treatment Of Type Ii Diabetes An Integrative Literature Review, Steven Lisowski

Grace Peterson Nursing Research Colloquium

A Low Carbohydrate, Ketogenic Diet for Treatment

of Type II Diabetes: An Integrative Literature Review

Steven Lisowski

Faculty Sponsor: Larry Maturin

Abstract

Background: Dietary modifications are commonly prescribed initial interventions in those recently diagnosed with type II diabetes. Presently, various researchers support that there is a growing body of evidence that advises to restrict carbohydrate intake to minimum levels to achieve optimal blood glucose levels and reduce complications related to poor diabetes management.

Objectives: To explore if the low carbohydrate, ketogenic diets (LCKD), in which carbohydrate intake of any kind is restricted, are very effective at reducing obesity and controlling …

Transcriptional Alterations In Hereditary And Sporadic Nonfunctioning Pancreatic Neuroendocrine Tumors According To Genotype., Xavier M Keutgen, Suresh Kumar, Sudheer Gara, Myriem Boufraqech, Sunita Agarwal, Ralph H Hruban, Naris Nilubol, Martha Quezado, Richard Finney, Maggie Cam, Electron Kebebew

Surgery Faculty Publications

BACKGROUND

Nonfunctioning pancreatic neuroendocrine tumors (NFPanNETs) may be sporadic or inherited because of germline mutations associated with von Hippel-Lindau disease (VHL) or multiple endocrine neoplasia type 1 (MEN1). The clinical behavior of NFPanNETs is difficult to predict, even in tumors of the same stage and grade. The authors analyzed genotype-specific patterns of transcriptional messenger RNA (mRNA) levels of NFPanNETs to understand the molecular features that determine PanNET phenotype.

METHODS

Thirty-two samples were included for genome-wide mRNA gene expression analysis (9 VHL-associated, 10 MEN1-associated, and 9 sporadic NFPanNETs and 4 purified normal islet cell [NIC] samples). Validation of genes was performed …

A Mirna Signature For Cognitive Deficits And Alcohol Use Disorder In Persons Living With Hiv/Aids, Dorota Wyczechowska, Hui-Yi Lin, Andrea Laplante, Duane Jeansonne, Adam Lassak, Christopher H. Parsons, Patricia E. Molina, Francesca Peruzzi

School of Medicine Faculty Publications

HIV-associated neurocognitive disorders (HAND) affects more than half of persons living with HIV-1/AIDS (PLWHA). Identification of biomarkers representing the cognitive status of PLWHA is a critical step for implementation of successful cognitive, behavioral and pharmacological strategies to prevent onset and progression of HAND. However, the presence of co-morbidity factors in PLWHA, the most common being substance abuse, can prevent the identification of such biomarkers. We have optimized a protocol to profile plasma miRNAs using quantitative RT-qPCR and found a miRNA signature with very good discriminatory ability to distinguish PLWHA with cognitive impairment from those without cognitive impairment. Here, we have …

Young Adults With Cleft Lip And Palate: Are They Receiving Team Services?, Sarah Widy, Andrea Bisceglia, Emily Bradley, Sanjana Kumari Vyda Srinivasa Kumar, Andrea Mcdowell, Amanda Murr, Blake Nowicki, Elisha Reed, Alexandria Staples, Brenda Louw

ETSU Faculty Works

It is widely acknowledged that a team approach is preferred practice and contributes to optimizing the surgical, dental, speech and psychosocial outcomes for individuals with CLP. Young adulthood often marks the transition from child-centered interdisciplinary care to adult-centered care. There is a paucity in literature relating to the transition of care for young adults with CLP. The purpose of this survey research is therefore to explore the CLP team practices regarding young adults with CLP.

Speech-Language Pathologists’ Perceptions Of Collaborating With Registered Dietitians In The Pediatric Population, Brenda Louw, Michelle Lee

ETSU Faculty Works

Survey research was conducted to explore Speech-Language Pathologists’ (SLPs) perceptions and experiences collaborating with Registered Dietitians (RDs) in the pediatric population. 107 SLPs in different settingsparticipated. Findings indicate SLPs were not exposed to RDs or the role of nutrition in their didactic and clinical training. Rather this exposure occurred once they were in the field practicing as an SLP. A clear need was identified regarding graduate and continued education on collaboration between SLPs and RDs.

A Time For Hope: Hdsa’S 50th Anniversary, A Record-Setting Gala, And The Impending Release Of Highly Anticipated Clinical Trial Results, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Precision Newborn Screening For Lysosomal Disorders, Melissa M. Minter Baerg, Stephanie D. Stoway, Jeremy Hart, Lea Mott, Dawn S. Peck, Stephanie L. Nett, Jason S. Eckerman, Jean M. Lacey, Coleman T. Turgeon, Dimitar Gavrilov, Devin Oglesbee, Kimiyo Raymond, Silvia Tortorelli, Dietrich Matern, Lars Mørkrid, Piero Rinaldo

Pathology and Laboratory Medicine Faculty Publications

Purpose: The implementation of newborn screening for lysosomal disorders has uncovered overall poor specificity, psychosocial harm experienced by caregivers, and costly follow-up testing of false-positive cases. We report an informatics solution proven to minimize these issues.

Methods: The Kentucky Department for Public Health outsourced testing for mucopolysaccharidosis type I (MPS I) and Pompe disease, conditions recently added to the recommended uniform screening panel, plus Krabbe disease, which was added by legislative mandate. A total of 55,161 specimens were collected from infants born over 1 year starting from February 2016. Testing by tandem mass spectrometry was integrated with multivariate pattern recognition …

Low Arousal Positive Emotional Stimuli Attenuate Aberrant Working Memory Processing In Persons With Mild Cognitive Impairment, Lucas S. Broster, Shonna L. Jenkins, Sarah D. Holmes, Gregory A. Jicha, Yang Jiang

Behavioral Science Faculty Publications

Emotional enhancement effects on memory have been reported to mitigate the pathophysiology of Alzheimer’s disease (AD). However, relative to their manifestation in persons without pathologic aging, these effects may be reduced in magnitude or even deleterious, especially in tasks that more closely model ecologic memory performance. Based upon a synthesis of such reports, we hypothesized that in persons with AD low arousal positive stimuli would evoke relatively intact emotional enhancement effects, but that high arousal negative stimuli would evoke disordered emotional enhancement effects. To assess this, participants with and without mild cognitive impairment (MCI) presumed to be due to AD …

I’M Going To Tell You A Little About Myself: Illness Centrality, Self-Image And Identity In Cystic Fibrosis, Susan Horky Lcsw, Laura Sherman Licsw, Julie K. Polvinen Ba, Medhavi Saxena Md, Michael Rich Md

Patient Experience Journal

This study assessed the illness centrality of adolescents with CF and the specific ways that CF may affect adolescents’ identities, through the qualitative analysis of video narratives. Adolescents with CF were loaned video cameras and asked to “show us your life outside the hospital” and to “teach your healthcare team about your CF.” Four major themes were identified related to illness centrality: CF is Central, CF is Compartmentalized, CF is Integrated into Self Image, CF is Denied. Integration and compartmentalization often co-existed. Four themes emerged related to the role of CF in self-image and identity: (1) Valence (positive or negative); …

Conference Proceedings: Aurora Scientific Day 2017

Journal of Patient-Centered Research and Reviews

This supplement includes select abstracts presented at the 43rd Annual Aurora Scientific Day research symposium on May 24, 2017. Aurora Scientific Day hosts a forum for original research conducted by faculty, fellows, residents, and other allied health professionals affiliated with Aurora Health Care, an integrated health system headquartered in Milwaukee, Wisconsin.

Sensitivity Of Current Methods For Diagnosing And Documenting Metabolic Syndrome Within A Large Community-Based Health Care System, Tiffany A. Mullen, Danielle M. Greer, Jennifer T. Fink, Renee E. Walker

Journal of Patient-Centered Research and Reviews

Background: Metabolic syndrome (MetS) is a constellation of metabolic conditions, including abdominal obesity, high blood pressure, high triglyceride level, low high-density-lipoprotein level and high fasting blood glucose level, that increase the risk of developing chronic health conditions. Various combinations of diagnostic criteria have been proposed, including those by the National Cholesterol Education Program Adult Treatment Panel III (ATP III), World Health Organization (WHO) and International Diabetes Foundation (IDF), among others. However, inconsistent use of diagnostic criteria and inadequate scientific evidence supporting use of specific criteria are current problems in health care.

Purpose: Quantify the prevalence of MetS diagnosis within the …

Generation Of A Patient-Derived Brain Metastasis Breast Cancer Cell Line Via Novel Orthotopic Injection Placement And Serial Mouse Transplantation To Develop Pdx Mouse Model, Amber L. Lacrosse, Denise M. Coley, Paul J. Mintz, Santhi D. Konduri, Richard A. Rovin, Amin B. Kassam

Journal of Patient-Centered Research and Reviews

Background: The incidence of brain metastasis appears to be increasing, potentially due to advanced technology that aids early diagnosis. Patient-derived xenografts (PDX) have high translational value, as these models retain key functional characteristics of the patient tumor. PDX models are useful to understand the molecular basis of tumorigenesis and to identify new treatment targets. However, generating a first-line PDX model is challenging as engraftment failure is high. Serial transplanting tumor tissue via mouse-to-mouse propagation increases engraftment rates and decreases PDX development time. Herein we report methods to generate a PDX cell line from patient-derived tumor tissue that includes the cerebral …

Six-Year Experience Of Influenza Vaccination As A Condition Of Employment For A Large Regional Health Care System, John R. Brill, Mark Hermanoff, Angela Tonozzi, Mary Jo Capodice, Jennifer Farrar, Zarina Dawoodbhai

Journal of Patient-Centered Research and Reviews

Background: Influenza remains a significant contributor to morbidity and mortality in the United States. Health care workers (HCW) can be both victims and vectors of influenza. Influenza vaccination of HCW is protective for both caregivers and patients, but voluntary programs generally fail to achieve rates recommended by the Centers for Disease Control and Prevention. Despite a complex, multifaceted influenza program initiated in 1996 that included significant education and promotion as well as free on-site vaccination, annual Aurora Health Care caregiver immunization rates remained in the mid-70s until adoption of a “condition of employment” strategy in 2011.

Purpose: Discuss the annual …

Assessment Of Chronic Disease To Determine Appropriateness Of Implantable Cardioverter-Defibrillator Therapy, Bilal M. Omery, Maharaj Singh, Randy S. Turkel, Robyn Shearer, Arshad Jahangir, M. Eyman Mortada, Jasbir S. Sra, Indrajit Choudhuri

Journal of Patient-Centered Research and Reviews

Background: Implantable cardioverter-defibrillator (ICD) therapy is considered appropriate when a patient is felt to have a reasonable expectation of 1-year survival. Chronic diseases have been estimated to be associated with greater than 10% annual mortality and may reduce benefits of ICD therapy. Frailty has been estimated to be associated with greater than 20% annual mortality and has been suggested to contraindicate ICD therapy.

Purpose: Determine a risk score that may identify patients in whom ICD implantation may not be appropriate.

Methods: Patients who received an ICD for primary and secondary prevention from 2008 through 2013 at the Aurora Health Care …