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Risk Of Post-Ercp Pancreatitis In Liver Transplant Patients: Single Center Experience, Shailender Singh Dec 2017

Risk Of Post-Ercp Pancreatitis In Liver Transplant Patients: Single Center Experience, Shailender Singh

Theses & Dissertations

Introduction: Acute pancreatitis remains the most common severe complication of endoscopic retrograde cholangiopancreatography (ERCP). The exact cause of post-ERCP pancreatitis (PEP) is unclear. Regardless of the mechanism that initiates PEP, the pathways of inflammation are similar to other forms of acute pancreatitis and include the activation of various inflammatory cytokines, released from the acinar cells and subsequently from helper T lymphocytes and macrophages. Liver transplants (LTx) patients on immunosuppressive medications have impaired T-cell response and hence decreased ability to generate these cytokines. The aim of this study was to review incidence rates and risk factors of PEP in this …


Cpap-Mad Combination Therapy For Cpap Intolerant Patients With Moderate To Severe Osa, Jacob Stadiem Dec 2017

Cpap-Mad Combination Therapy For Cpap Intolerant Patients With Moderate To Severe Osa, Jacob Stadiem

Theses & Dissertations

The treatment of obstructive sleep apnea (OSA) allows for a multidisciplinary approach between dentistry and medicine. Continuous positive airway pressure (CPAP) is the gold standard for OSA treatment, but the non-adherence rates are high. The mandibular advancement device (MAD) has a higher acceptance rate than the CPAP, however the efficacy is much lower in cases of moderate to severe OSA. This thesis attempted to evaluate if there was a change in compliance when a MAD was added as a combination therapy to moderate to severe OSA subjects that were currently non-compliant with their CPAP. In addition, the change in air …


Novel Therapeutic Strategies For Treatment Of Castration-Resistant Prostate Cancer, Matthew A. Ingersoll Dec 2017

Novel Therapeutic Strategies For Treatment Of Castration-Resistant Prostate Cancer, Matthew A. Ingersoll

Theses & Dissertations

Prostate cancer (PCa) remains the most commonly diagnosed solid tumor and is the third leading cause of cancer-related death in United States men. While androgen deprivation therapy is the current standard-of-care treatment for metastatic PCa, most patients eventually relapse and develop castration-resistant (CR) tumors, for which there is currently no effective treatment. Therefore, synthesis of novel therapeutic agents and identification of alternative target proteins are necessary to improve treatment. Herein, I investigate the efficacy of novel imidazopyridine and statin derivatives as alternative therapeutic compounds. These molecules not only inhibit androgen receptor signaling, but also block activation of the AKT axis, …


Frequently Identified Gaps In Antibiotic Stewardship Programs In Critical Access Hospitals, Philip Chung, Regina Nailon, Kate Tyner, Sue Beach, Scott Bergman, Margaret Drake, Teresa Fitzgerald, Elizabeth Lyden, Mark Rupp, Michelle Schwedhelm, Maureen Tierney-Brenran, Trevor Van Schooneveld, Muhammad Salman Ashraf Oct 2017

Frequently Identified Gaps In Antibiotic Stewardship Programs In Critical Access Hospitals, Philip Chung, Regina Nailon, Kate Tyner, Sue Beach, Scott Bergman, Margaret Drake, Teresa Fitzgerald, Elizabeth Lyden, Mark Rupp, Michelle Schwedhelm, Maureen Tierney-Brenran, Trevor Van Schooneveld, Muhammad Salman Ashraf

Posters and Presentations: Nebraska ASAP

Background: Nebraska (NE) Infection Control Assessment and Promotion Program (ICAP) is a CDC funded project. ICAP team works in collaboration with NE Department of Health and Human Services (NEDHHS) to assess and improve infection prevention and control programs (IPCP) in various health care settings including resource limited settings like critical access hospitals (CAH). Little is known about the existing gaps in antimicrobial stewardship programs (ASP) of CAH. Hence, we decided to study the current level of ASP activities and factors associated with these activities in CAH.

Methods: NE ICAP conducted on-site surveys in 36 CAH from October 2015 to February …


The Interprofessional Academy Of Educators: Inclusive, Collaborative, Innovative, Tanya M. Custer, Kim Michael Oct 2017

The Interprofessional Academy Of Educators: Inclusive, Collaborative, Innovative, Tanya M. Custer, Kim Michael

Posters and Presentations: Medical Imaging & Therapeutic Sciences

Issue to be addressed: To elevate the educational mission of the institution, UNMC established the Interprofessional Academy of Educators in 2016. Designed by educators for educators, this interprofessional community strives to improve health professions education by encouraging curricular innovation, supporting educational scholarship & offering mentorship for early career and seasoned educators.

Method: The inaugural class included a unique blend of medical scholars from 8 Colleges, 2 Institutes, Academic Affairs, IT Services, and Library Sciences. Members span a 500-mile wide campus. Eight SIGs foster interprofessional collaboration & scholarship. An academically diverse leadership team of five oversees the Academy.


Bedtime Fading With Response Cost For Treatment Of Sleep Disturbances In Children With Autism Spectrum Disorder, Sela Ann Sanberg Aug 2017

Bedtime Fading With Response Cost For Treatment Of Sleep Disturbances In Children With Autism Spectrum Disorder, Sela Ann Sanberg

Theses & Dissertations

As many as 82% of children with Autism Spectrum Disorders (ASD) experience numerous chronic sleep-related problems and at a much higher frequency and severity than their typically developing peers. Behavioral treatments are considered best practice and first-line treatment to address sleep problems. These treatments tend to address one specific sleep-related behavior at a time. Bedtime Fading with Response Cost (BFRC) is a promising intervention that targets a multitude of sleep problems concurrently and has yet to be replicated by more than one investigative team in the home setting with children on the autism spectrum. This study evaluated the effectiveness of …


Dnmt3a Haploinsufficiency Provokes Hematologic Malignancy Of B-Lymphoid, T-Lymphoid, And Myeloid Lineage In Mice, Garland Michael Upchurch Aug 2017

Dnmt3a Haploinsufficiency Provokes Hematologic Malignancy Of B-Lymphoid, T-Lymphoid, And Myeloid Lineage In Mice, Garland Michael Upchurch

Theses & Dissertations

DNA methyltransferase 3A (DNMT3A) is a master epigenetic regulator of benign and malignant hematopoiesis. To dissect the biological consequences of homozygous and heterozygous Dnmt3a inactivation in malignant hematopoiesis, we generated Dnmt3a homozygous null (Dnmt3aΔ/Δ) and Dnmt3a heterozygous (Dnmt3a+/) mice and compared the presentations of hematologic malignancies between cohorts. Bi-allelic inactivation of Dnmt3a results in the presentation of mature lymphoid neoplasms resembling chronic lymphocytic leukemia (CLL; B220+CD19+CD5+; 88% penetrance (37/42)) and CD8+ peripheral T-cell lymphoma (PTCL; TCRβ+CD3+CD8+CD4; 40% penetrance (17/42)). …


Synaptic Ribbon Active Zones In Cone Photoreceptors Operate Independently From One Another., Justin J. Grassmeyer, Wallace B. Thoreson Jul 2017

Synaptic Ribbon Active Zones In Cone Photoreceptors Operate Independently From One Another., Justin J. Grassmeyer, Wallace B. Thoreson

Journal Articles: Ophthalmology

Cone photoreceptors depolarize in darkness to release glutamate-laden synaptic vesicles. Essential to release is the synaptic ribbon, a structure that helps organize active zones by clustering vesicles near proteins that mediate exocytosis, including voltage-gated Ca(2+) channels. Cone terminals have many ribbon-style active zones at which second-order neurons receive input. We asked whether there are functionally significant differences in local Ca(2+) influx among ribbons in individual cones. We combined confocal Ca(2+) imaging to measure Ca(2+) influx at individual ribbons and patch clamp recordings to record whole-cell ICa in salamander cones. We found that the voltage for half-maximal activation (V50) of whole …


Vitamin D Supplementation In Allo-Hsct Patients, Bailey Nelson May 2017

Vitamin D Supplementation In Allo-Hsct Patients, Bailey Nelson

Theses & Dissertations

BACKGROUND: Bone health is a serious concern for long-term survivors of Allo-HSCT due to multiple risk factors including steroids, chemotherapy, immunosuppressive drugs, and poor nutrition status1. Steroids have been long proven to have negative impact on bone health and the National Osteoporosis Foundation (NOF) lists steroids as a contributing factor to osteoporosis and fractures. NOF guidelines recommend providing adequate daily vitamin D as a safe and inexpensive way to help reduce fracture risk1. Therefore, proper supplementation of vitamin D may increase the quality of life for patients post Allo-HSCT.

PURPOSE: The purpose of this study is to determine if Allo-HSCT …


Epigenetic Modifications Of Human Placenta Associated With Preterm Birth, Drissa Toure May 2017

Epigenetic Modifications Of Human Placenta Associated With Preterm Birth, Drissa Toure

Theses & Dissertations

Preterm birth is a complex multifactorial process. Despite the well-known role of the placenta in supporting the fetal development and maternal-fetal tolerance, the placental epigenetic modifications and preterm birth (PTB) remains poorly understood and under investigated. Various maternal and environment factors can influence epigenetic programming during fetal development to affect the functioning and structures of organs, including the placenta, which can lead to adverse pregnancy outcomes, including PTB. The understanding of the placental epigenetic alterations and maternal determinants associated with PTB are apparently indispensable for the development of actual diagnosis and methods of prevention and treatment of premature labor. The …


The Rise And Fall Of The Bovine Corpus Luteum, Heather Talbott May 2017

The Rise And Fall Of The Bovine Corpus Luteum, Heather Talbott

Theses & Dissertations

This dissertation describes a study of the mechanisms regulating the genesis and subsequent involution of the temporary endocrine structure, the corpus luteum (CL), through the use of a bovine model. The CL is essential for maintaining a suitable uterine environment for embryo implantation and early development through secretion of the steroid hormone progesterone. The “Rise and Fall” of the CL occurs within each estrous cycle whereby the CL must form from the ruptured follicle, secrete sufficient progesterone for uterine maturation, and at the end of the cycle (or pregnancy) regress to allow new follicular development. During the rise of the …


Tgfβ/Smad3 Regulates Proliferation And Apoptosis Through Irs-1 Inhibition In Colon Cancer Cells., Katie L. Bailey, Ekta Agarwal, Sanjib Chowdhury, Jiangtao Luo, Michael G. Brattain, Jennifer D. Black, J. Wang Apr 2017

Tgfβ/Smad3 Regulates Proliferation And Apoptosis Through Irs-1 Inhibition In Colon Cancer Cells., Katie L. Bailey, Ekta Agarwal, Sanjib Chowdhury, Jiangtao Luo, Michael G. Brattain, Jennifer D. Black, J. Wang

Journal Articles: Eppley Institute

In this study, we have uncovered a novel crosstalk between TGFβ and IGF-1R signaling pathways. We show for the first time that expression and activation of IRS-1, an IGF-1R adaptor protein, is decreased by TGFβ/Smad3 signaling. Loss or attenuation of TGFβ activation leads to elevated expression and phosphorylation of IRS-1 in colon cancer cells, resulting in enhanced cell proliferation, decreased apoptosis and increased tumor growth in vitro and in vivo. Downregulation of IRS-1 expression reversed Smad3 knockdown-mediated oncogenic phenotypes, indicating that TGFβ/Smad3 signaling inhibits cell proliferation and increases apoptosis at least partially through the inhibition of IRS-1 expression and activation. …


Cigarette Smoke Impairs A2a Adenosine Receptor Mediated Wound Repair Through Up-Regulation Of Duox-1 Expression., Zhi Tian, Hui Zhang, Jendayi Dixon, Nicole Traphagen, Todd A. Wyatt, Kusum K. Kharbanda, Samantha Simet, Narasaiah Kolliputi, Diane S Allen-Gipson Mar 2017

Cigarette Smoke Impairs A2a Adenosine Receptor Mediated Wound Repair Through Up-Regulation Of Duox-1 Expression., Zhi Tian, Hui Zhang, Jendayi Dixon, Nicole Traphagen, Todd A. Wyatt, Kusum K. Kharbanda, Samantha Simet, Narasaiah Kolliputi, Diane S Allen-Gipson

Journal Articles: Pulmonary & Critical Care Med

Cigarette smoke (CS) exposure and intrinsic factors such as the NADPH oxidases produce high levels of reactive oxygen species (ROS), ensuing inflammatory tissue injury. We previously demonstrated that CS-generated ROS, particularly hydrogen peroxide (H2O2), impaired adenosine stimulated wound repair. We hypothesized that CS exposure modulates expression of Dual oxidase 1 (Duox-1), a NADPH oxidases known to generate H2O2. To test this hypothesis, we used human bronchial epithelial cell line Nuli-1 and C57BL/6 mice. Cells were treated with 5% CS extract (CSE) for various periods of time, and mice were exposed to whole body CS for six weeks. Both CSE and …


Effect Of Low-Level Co2 On Innate Inflammatory Protein Response To Organic Dust From Swine Confinement Barns., David Schneberger, Jane M. Devasure, Kristina L. Bailey, Debra J. Romberger, Todd A. Wyatt Mar 2017

Effect Of Low-Level Co2 On Innate Inflammatory Protein Response To Organic Dust From Swine Confinement Barns., David Schneberger, Jane M. Devasure, Kristina L. Bailey, Debra J. Romberger, Todd A. Wyatt

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Organic hog barn dust (HDE) exposure induces lung inflammation and long-term decreases in lung function in agricultural workers. While concentrations of common gasses in confined animal facilities are well characterized, few studies have been done addressing if exposure to elevated barn gasses impacts the lung immune response to organic dusts. Given the well documented effects of hypercapnia at much higher levels we hypothesized that CO2 at 8 h exposure limit levels (5000 ppm) could alter innate immune responses to HDE.

METHODS: Using a mouse model, C57BL/6 mice were nasally instilled with defined barn dust extracts and then housed in …


Effect Of Low-Level Co2 On Innate Inflammatory Protein Response To Organic Dust From Swine Confinement Barns., David Schneberger, Jane M. Devasure, Kristina L. Bailey, Debra J. Romberger, Todd A. Wyatt Mar 2017

Effect Of Low-Level Co2 On Innate Inflammatory Protein Response To Organic Dust From Swine Confinement Barns., David Schneberger, Jane M. Devasure, Kristina L. Bailey, Debra J. Romberger, Todd A. Wyatt

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Organic hog barn dust (HDE) exposure induces lung inflammation and long-term decreases in lung function in agricultural workers. While concentrations of common gasses in confined animal facilities are well characterized, few studies have been done addressing if exposure to elevated barn gasses impacts the lung immune response to organic dusts. Given the well documented effects of hypercapnia at much higher levels we hypothesized that CO2 at 8 h exposure limit levels (5000 ppm) could alter innate immune responses to HDE.

METHODS: Using a mouse model, C57BL/6 mice were nasally instilled with defined barn dust extracts and then housed in …


Interaction Of Cd14 Haplotypes And Soluble Cd14 On Pulmonary Function In Agricultural Workers., Tricia D. Levan, Lynette M. Smith, Art J. Heires, Ted R. Mikuls, Jane L. Meza, Lisa A. Weissenburger-Moser, Debra J. Romberger Mar 2017

Interaction Of Cd14 Haplotypes And Soluble Cd14 On Pulmonary Function In Agricultural Workers., Tricia D. Levan, Lynette M. Smith, Art J. Heires, Ted R. Mikuls, Jane L. Meza, Lisa A. Weissenburger-Moser, Debra J. Romberger

Journal Articles: Internal Medicine

BACKGROUND: Agricultural environments are contaminated with organic dusts containing bacterial components. Chronic inhalation of organic dusts is implicated in respiratory diseases. CD14 is a critical receptor for gram-negative lipopolysaccharide; however, its association with respiratory disease among agricultural workers is unknown. The objective of this study was to determine if serum soluble CD14 (sCD14) levels are associated with lung function among agricultural workers and if this association is modified by genetic variants in CD14.

METHODS: This cross-sectional study included 584 veterans with >2 years of farming experience and that were between the ages of 40 and 80 years. Participants underwent spirometry …


Memri Is A Biomarker Defining Nicotine-Specific Neuronal Responses In Subregions Of The Rodent Brain., Aditya N. Bade, Howard Gendelman, Michael D. Boska, Yutong Liu Feb 2017

Memri Is A Biomarker Defining Nicotine-Specific Neuronal Responses In Subregions Of The Rodent Brain., Aditya N. Bade, Howard Gendelman, Michael D. Boska, Yutong Liu

Journal Articles: Radiology

Nicotine dependence is defined by dopaminergic neuronal activation within the nucleus accumbens (ACB) and by affected neural projections from nicotine-stimulated neurons. Control of any subsequent neural activities would underpin any smoking cessation strategy. While extensive efforts have been made to study the pathophysiology of nicotine addiction, more limited works were developed to find imaging biomarkers. If such biomarkers are made available, addictive behaviors could be monitored noninvasively. To such ends, we employed manganese (Mn(2+))-enhanced magnetic resonance imaging (MEMRI) to determine whether it could be used to monitor neuronal activities after acute and chronic nicotine exposure in rats. The following were …


Aberrant Neuronal Dynamics During Working Memory Operations In The Aging Hiv-Infected Brain., Tony W. Wilson, Amy L. Proskovec, Elizabeth Heinrichs-Graham, Jennifer O'Neill, Kevin R. Robertson, Howard S. Fox, Susan Swindells Feb 2017

Aberrant Neuronal Dynamics During Working Memory Operations In The Aging Hiv-Infected Brain., Tony W. Wilson, Amy L. Proskovec, Elizabeth Heinrichs-Graham, Jennifer O'Neill, Kevin R. Robertson, Howard S. Fox, Susan Swindells

Journal Articles: Infectious Diseases

Impairments in working memory are among the most prevalent features of HIV-associated neurocognitive disorders (HAND), yet their origins are unknown, with some studies arguing that encoding operations are disturbed and others supporting deficits in memory maintenance. The current investigation directly addresses this issue by using a dynamic mapping approach to identify when and where processing in working memory circuits degrades. HIV-infected older adults and a demographically-matched group of uninfected controls performed a verbal working memory task during magnetoencephalography (MEG). Significant oscillatory neural responses were imaged using a beamforming approach to illuminate the spatiotemporal dynamics of neuronal activity. HIV-infected patients were …


Novel Long-Chain Compounds With Both Immunomodulatory And Mena Inhibitory Activities Against Staphylococcus Aureus And Its Biofilm., Seoung-Ryoung Choi, Joel Frandsen, Prabagaran Narayanasamy Jan 2017

Novel Long-Chain Compounds With Both Immunomodulatory And Mena Inhibitory Activities Against Staphylococcus Aureus And Its Biofilm., Seoung-Ryoung Choi, Joel Frandsen, Prabagaran Narayanasamy

Journal Articles: Pathology and Microbiology

Menaquinone (MK) biosynthesis pathway is a potential target for evaluating antimicrobials in gram-positive bacteria. Here, 1,4-dihydroxy-2-naphthoate prenyltransferase (MenA) was targeted to reduce methicillin-resistant Staphylococcus aureus (MRSA) growth. MenA inhibiting, long chain-based compounds were designed, synthesized and evaluated against MRSA and menaquinone utilizing bacteria in aerobic conditions. The results showed that these bacteria were susceptible to most of the compounds. Menaquinone (MK-4) supplementation rescued MRSA growth, suggesting these compounds inhibit MK biosynthesis. 3a and 7c exhibited promising inhibitory activities with MICs ranging 1-8 μg/mL against MRSA strains. The compounds did not facilitate small colony variant formation. These compounds also inhibited the …


Neuroprotection Through Flavonoid: Enhancement Of The Glyoxalase Pathway., Joel Frandsen, Prabagaran Narayanasamy Jan 2017

Neuroprotection Through Flavonoid: Enhancement Of The Glyoxalase Pathway., Joel Frandsen, Prabagaran Narayanasamy

Journal Articles: Pathology and Microbiology

The glyoxalase pathway functions to detoxify reactive dicarbonyl compounds, most importantly methylglyoxal. The glyoxalase pathway is an antioxidant defense mechanism that is essential for neuroprotection. Excessive concentrations of methylglyoxal have deleterious effects on cells, leading to increased levels of inflammation and oxidative stress. Neurodegenerative diseases - including Alzheimer's, Parkinson's, Aging and Autism Spectrum Disorder - are often induced or exacerbated by accumulation of methylglyoxal. Antioxidant compounds possess several distinct mechanisms that enhance the glyoxalase pathway and function as neuroprotectants. Flavonoids are well-researched secondary plant metabolites that appear to be effective in reducing levels of oxidative stress and inflammation in neural …


Interleukin (Il)-18 Binding Protein Deficiency Disrupts Natural Killer Cell Maturation And Diminishes Circulating Il-18., Robert Z. Harms, Austin J. Creer, Kristina M. Lorenzo-Arteaga, Katie R. Ostlund, Nora Sarvetnick Jan 2017

Interleukin (Il)-18 Binding Protein Deficiency Disrupts Natural Killer Cell Maturation And Diminishes Circulating Il-18., Robert Z. Harms, Austin J. Creer, Kristina M. Lorenzo-Arteaga, Katie R. Ostlund, Nora Sarvetnick

Journal Articles: Surgery

The cytokine interleukin (IL)-18 is a crucial amplifier of natural killer (NK) cell function. IL-18 signaling is regulated by the inhibitory effects of IL-18 binding protein (IL-18BP). Using mice deficient in IL-18BP (IL-18BPKO), we investigated the impact of mismanaged IL-18 signaling on NK cells. We found an overall reduced abundance of splenic NK cells in the absence of IL-18BP. Closer examination of NK cell subsets in spleen and bone marrow using CD27 and CD11b expression revealed that immature NK cells were increased in abundance, while the mature population of NK cells was reduced. Also, NK cells were polarized to greater …


Multimodal Theranostic Nanoformulations Permit Magnetic Resonance Bioimaging Of Antiretroviral Drug Particle Tissue-Cell Biodistribution, Bhavesh D. Kevadiya, Christopher J. Woldstad, Brendan M. Ottemann, Prasanta Dash, Balasrinivasa R. Sajja, Benjamin G. Lamberty, Brenda M. Morsey, Ted Kocher, Rinku Dutta, Aditya N. Bade, Yutong Liu, Shannon E. Callen, Howard S. Fox, Siddappa N. Byrareddy, Joellyn M. Mcmillan, Tatiana K. Bronich, Benson J. Edagwa, Michael D. Boska, Howard Gendelman Jan 2017

Multimodal Theranostic Nanoformulations Permit Magnetic Resonance Bioimaging Of Antiretroviral Drug Particle Tissue-Cell Biodistribution, Bhavesh D. Kevadiya, Christopher J. Woldstad, Brendan M. Ottemann, Prasanta Dash, Balasrinivasa R. Sajja, Benjamin G. Lamberty, Brenda M. Morsey, Ted Kocher, Rinku Dutta, Aditya N. Bade, Yutong Liu, Shannon E. Callen, Howard S. Fox, Siddappa N. Byrareddy, Joellyn M. Mcmillan, Tatiana K. Bronich, Benson J. Edagwa, Michael D. Boska, Howard Gendelman

Journal Articles: Radiology

RATIONALE: Long-acting slow effective release antiretroviral therapy (LASER ART) was developed to improve patient regimen adherence, prevent new infections, and facilitate drug delivery to human immunodeficiency virus cell and tissue reservoirs. In an effort to facilitate LASER ART development, “multimodal imaging theranostic nanoprobes” were created. These allow combined bioimaging, drug pharmacokinetics and tissue biodistribution tests in animal models.

METHODS: Europium (Eu3+)- doped cobalt ferrite (CF) dolutegravir (DTG)- loaded (EuCF-DTG) nanoparticles were synthesized then fully characterized based on their size, shape and stability. These were then used as platforms for nanoformulated drug biodistribution.

RESULTS: Folic acid (FA) decoration of …


Atrial Fibrillation Induction In A Pediatric Patient During Adenosine Administration, Jeffrey A. Robinson, Christopher S. Snyder Jan 2017

Atrial Fibrillation Induction In A Pediatric Patient During Adenosine Administration, Jeffrey A. Robinson, Christopher S. Snyder

Journal Articles: Pediatrics

Adenosine by rapid intravenous bolus is frequently utilized in clinical practice as both a pharmacologic treatment for supraventricular (reentrant) tachycardia and in provocative testing for the diagnosis of Wolff-Parkinson-White (WPW) syndrome. This is a case report of an otherwise healthy adolescent female who received adenosine during a provocative test for WPW syndrome. Immediately after receiving adenosine, the patient had a self-limited episode of atrial fibrillation. When administering adenosine, teams should be aware of the potential adverse effects and be prepared to treat appropriately.


Genomic Alterations In Mucins Across Cancers, Ryan King, Fang Yu, Pankaj K. Singh Jan 2017

Genomic Alterations In Mucins Across Cancers, Ryan King, Fang Yu, Pankaj K. Singh

Journal Articles: Eppley Institute

The significance of mucins in cancers has led to the development of novel biomarkers and therapeutic agents against cancers. Despite significant advances in the understanding of mucins, systemic investigations into the role of mucins in cancer biology focusing particularly on the histological subtypes and stages, along with other variables, are yet to be carried out to discover potential novel functions and cancer-specific roles. Here, we investigated 11 mucin expressing cancers for DNA mutations, mRNA expression, copy number, methylation, and the impacts these genomic features may have on patient survival by utilizing The Cancer Genome Atlas dataset. We demonstrate that mucin …


A Role For B Cells In Organic Dust Induced Lung Inflammation, Jill A. Poole, Ted R. Mikuls, Michael J. Duryee, Kristi J. Warren, Todd A. Wyatt, Amy J. Nelson, Debra J. Romberger, William W. West, Geoffrey M. Thiele Jan 2017

A Role For B Cells In Organic Dust Induced Lung Inflammation, Jill A. Poole, Ted R. Mikuls, Michael J. Duryee, Kristi J. Warren, Todd A. Wyatt, Amy J. Nelson, Debra J. Romberger, William W. West, Geoffrey M. Thiele

Journal Articles: Internal Medicine

BACKGROUND: Agriculture organic dust exposures induce lung disease with lymphoid aggregates comprised of both T and B cells. The precise role of B cells in mediating lung inflammation is unknown, yet might be relevant given the emerging role of B cells in obstructive pulmonary disease and associated autoimmunity.

METHODS: Using an established animal model, C57BL/6 wild-type (WT) and B-cell receptor (BCR) knock-out (KO) mice were repetitively treated with intranasal inhalation of swine confinement organic dust extract (ODE) daily for 3 weeks and lavage fluid, lung tissues, and serum were collected.

RESULTS: ODE-induced neutrophil influx in lavage fluid was not reduced …


Recent Advances In The Management And Understanding Of Diabetic Retinopathy, Matthew Powers, Margaret Greven, Robert Kleinman, Quan D. Nguyen, Diana V. Do Jan 2017

Recent Advances In The Management And Understanding Of Diabetic Retinopathy, Matthew Powers, Margaret Greven, Robert Kleinman, Quan D. Nguyen, Diana V. Do

Journal Articles: Ophthalmology

Despite recent advances in the diagnosis and treatment of diabetic retinopathy, this complication remains a steadfast challenge to patients and physicians. This review summarizes recent progress in the diagnosis and management of diabetic retinopathy, including automated screening, optical coherence tomography, control of systemic risk factors, surgical techniques, laser treatment, and pharmaceutical treatment, including vascular endothelial growth factor inhibitors. Recent advances in pharmaceutical treatments, in particular, hold strong promise of halting and sometimes reversing the disease process. Clinicians nevertheless must remain vigilant in their efforts to diagnose and treat this disease early in its course.


The Distinct Metabolic Phenotype Of Lung Squamous Cell Carcinoma Defines Selective Vulnerability To Glycolytic Inhibition, Justin Goodwin, Michael L. Neugent, Shin Yup Lee, Joshua H. Choe, Hyunsung Choi, Dana M. R. Jenkins, Robin J. Ruthenborg, Maddox W. Robinson, Ji Yun Jeong, Masaki Wake, Hajime Abe, Norihiko Takeda, Hiroko Endo, Masahiro Inoue, Zhenyu Xuan, Hyuntae Yoo, Min Chen, Jung-Mo Ahn, John D. Minna, Kristi L. Helke, Pankaj K. Singh, David B. Shackelford, Jung-Whan Kim Jan 2017

The Distinct Metabolic Phenotype Of Lung Squamous Cell Carcinoma Defines Selective Vulnerability To Glycolytic Inhibition, Justin Goodwin, Michael L. Neugent, Shin Yup Lee, Joshua H. Choe, Hyunsung Choi, Dana M. R. Jenkins, Robin J. Ruthenborg, Maddox W. Robinson, Ji Yun Jeong, Masaki Wake, Hajime Abe, Norihiko Takeda, Hiroko Endo, Masahiro Inoue, Zhenyu Xuan, Hyuntae Yoo, Min Chen, Jung-Mo Ahn, John D. Minna, Kristi L. Helke, Pankaj K. Singh, David B. Shackelford, Jung-Whan Kim

Journal Articles: Eppley Institute

Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small cell lung cancer (NSCLC) and are distinct in their histological, molecular and clinical presentation. However, metabolic signatures specific to individual NSCLC subtypes remain unknown. Here, we perform an integrative analysis of human NSCLC tumour samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas (TCGA) and reveal a markedly elevated expression of the GLUT1 glucose transporter in lung SqCC, which augments glucose uptake and glycolytic flux. We show that a critical reliance on glycolysis renders lung SqCC vulnerable to glycolytic inhibition, …


Muc1 Facilitates Metabolomic Reprogramming In Triple-Negative Breast Cancer, Gennifer Goode, Venugopal Gunda, Nina V. Chaika, Vinee Purohit, Fang Yu, Pankaj K. Singh Jan 2017

Muc1 Facilitates Metabolomic Reprogramming In Triple-Negative Breast Cancer, Gennifer Goode, Venugopal Gunda, Nina V. Chaika, Vinee Purohit, Fang Yu, Pankaj K. Singh

Journal Articles: Eppley Institute

BACKGROUND: Mucin1 (MUC1), a glycoprotein associated with chemoresistance and an aggressive cancer phenotype, is aberrantly overexpressed in triple-negative breast cancer (TNBC). Recent studies suggest that MUC1 plays a role in modulating cancer cell metabolism and thereby supports tumor growth. Herein, we examined the role of MUC1 in metabolic reprogramming in TNBC.

METHODS: MUC1 was stably overexpressed in MDA-MB-231 TNBC cells and stably knocked down in MDA-MB-468 cells. We performed liquid chromatography-coupled tandem mass spectrometry-assisted metabolomic analyses and physiological assays, which indicated significant alterations in the metabolism of TNBC cells due to MUC1 expression.

RESULTS: Differential analyses identified significant differences in …


Transcriptomic And Bioinformatics Analysis Of The Early Time-Course Of The Response To Prostaglandin F2 Alpha In The Bovine Corpus Luteum., Heather Talbott, Xiaoying Hou, Fang Qiu, Pan Zhang, Chittibabu Guda, Fang Yu, Robert A. Cushman, Jennifer R. Wood, Cheng Wang, Andrea S. Cupp, John S. Davis Jan 2017

Transcriptomic And Bioinformatics Analysis Of The Early Time-Course Of The Response To Prostaglandin F2 Alpha In The Bovine Corpus Luteum., Heather Talbott, Xiaoying Hou, Fang Qiu, Pan Zhang, Chittibabu Guda, Fang Yu, Robert A. Cushman, Jennifer R. Wood, Cheng Wang, Andrea S. Cupp, John S. Davis

Journal Articles: Obstetrics & Gynecology

RNA expression analysis was performed on the corpus luteum tissue at five time points after prostaglandin F2 alpha treatment of midcycle cows using an Affymetrix Bovine Gene v1 Array. The normalized linear microarray data was uploaded to the NCBI GEO repository (GSE94069). Subsequent statistical analysis determined differentially expressed transcripts ± 1.5-fold change from saline control with P ≤ 0.05. Gene ontology of differentially expressed transcripts was annotated by DAVID and Panther. Physiological characteristics of the study animals are presented in a figure. Bioinformatic analysis by Ingenuity Pathway Analysis was curated, compiled, and presented in tables. A dataset comparison with similar …


Gallium Nanoparticles Facilitate Phagosome Maturation And Inhibit Growth Of Virulent Mycobacterium Tuberculosis In Macrophages., Seoung-Ryoung Choi, Bradley E. Britigan, David M. Moran, Prabagaran Narayanasamy Jan 2017

Gallium Nanoparticles Facilitate Phagosome Maturation And Inhibit Growth Of Virulent Mycobacterium Tuberculosis In Macrophages., Seoung-Ryoung Choi, Bradley E. Britigan, David M. Moran, Prabagaran Narayanasamy

Journal Articles: Pathology and Microbiology

New treatments and novel drugs are required to counter the growing problem of drug-resistant strains of Mycobacterium tuberculosis (M.tb). Our approach against drug resistant M.tb, as well as other intracellular pathogens, is by targeted drug delivery using nanoformulations of drugs already in use, as well as drugs in development. Among the latter are gallium (III) (Ga)-based compounds. In the current work, six different types of Ga and rifampin nanoparticles were prepared in such a way as to enhance targeting of M.tb infected-macrophages. They were then tested for their ability to inhibit growth of a fully pathogenic strain (H37Rv) or a …