Medicine and Health Sciences Commons^™

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, …

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 …

2016 Refugee Health Needs Assessment In Omaha, Nebraska, Kandy Do, Drissa Toure, Naw Latt Nlam, Dejun Su

Posters and Presentations: College of Public Health

Refugees resettling to Nebraska undeniably have different health needs compared to native Nebraska residents. Capturing those differences is the start to catering local health care to refugees. A health needs assessment of refugees in Omaha, Nebraska seek to assess their perceived needs, barriers, and preferences regarding health care, in order to address them justly. The refugee population in Omaha, Nebraska has exponentially increased over the past decade and will continue to increase, bringing global health matters to our backyard. The data and results from surveying over 290 refugees will guide health care organizations and services to appropriately serve refugees and …

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

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 …

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.

Kiss-And-Run Is A Significant Contributor To Synaptic Exocytosis And Endocytosis In Photoreceptors., Xiangyi Wen, Grant W. Saltzgaber, Wallace B. Thoreson

Journal Articles: Pharmacology & Experimental Neuroscience

Accompanying sustained release in darkness, rod and cone photoreceptors exhibit rapid endocytosis of synaptic vesicles. Membrane capacitance measurements indicated that rapid endocytosis retrieves at least 70% of the exocytotic membrane increase. One mechanism for rapid endocytosis is kiss-and-run fusion where vesicles briefly contact the plasma membrane through a small fusion pore. Release can also occur by full-collapse in which vesicles merge completely with the plasma membrane. We assessed relative contributions of full-collapse and kiss-and-run in salamander photoreceptors using optical techniques to measure endocytosis and exocytosis of large vs. small dye molecules. Incubation with small dyes (SR101, 1 nm; 3-kDa dextran-conjugated …

Proteome Analysis Of Bronchoalveolar Lavage From Calves Infected With Bovine Respiratory Syncytial Virus-Insights In Pathogenesis And Perspectives For New Treatments., Sara Hägglund, Krister Blodörn, Katarina Näslund, Karin Vargmar, Sara Bergström Lind, Jia Mi, Mariluz Araínga, Sabine Riffault, Geraldine Taylor, John Pringle, Jean François Valarcher

Journal Articles: Pharmacology & Experimental Neuroscience

Human and bovine respiratory syncytial viruses (HRSV/BRSV) are major causes of severe lower respiratory tract infections in children and calves, respectively. Shared epidemiological, clinical, pathological and genetic characteristics of these viruses make comparative research highly relevant. To characterise the host response against BRSV infection, bronchoalveolar lavage supernatant (BAL) from i) non-vaccinated, BRSV-infected ii) vaccinated, BRSV-infected and iii) non-infected calves was analysed by tandem mass spectrometry. Proteins were semi-quantified and protein expression was validated by immunoblotting. Correlations between selected proteins and pathology, clinical signs and virus shedding were investigated. Calves with BRSV-induced disease had increased total protein concentrations and a decreased …

Body Mass Index Change In Gastrointestinal Cancer And Chronic Obstructive Pulmonary Disease Is Associated With Dedicator Of Cytokinesis 1, Merry-Lynn Noelle Mcdonald, Sungho Won, Manuel Mattheisen, Peter J. Castaldi, Michael H. Cho, Erica Rutten, Megan Hardin, Wai-Ki Yip, Stephen I. Rennard, David A. Lomas, Emiel F.M. Wouters, Alvar Agusti, Richard Casaburi, Christoph P. Lange, George O'Connor, Craig P. Hersh, Edwin K. Silverman

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: There have been a number of candidate gene association studies of cancer cachexia-related traits, but no genome-wide association study (GWAS) has been published to date. Cachexia presents in patients with a number of complex traits, including both cancer and COPD. The objective of the current investigation was to search for a shared genetic aetiology for change in body mass index (ΔBMI) among cancer and COPD by using GWAS data in the Framingham Heart Study.

METHODS: A linear mixed effects model accounting for age, sex, and change in smoking status was used to calculate ΔBMI in participants over 40 years …

Reliability Of Medical Records In Diagnosing Inflammatory Breast Cancer In Egypt, Lynne Le, Catherine Schairer, Ahmed Hablas, Jane L. Meza, Shinobu Watanabe-Galloway, Mohamed Ramadan, Sofia D. Merajver, Ibrahim A. Seifeldin, Amr S. Soliman

Journal Articles: Epidemiology

BACKGROUND: Inflammatory breast cancer (IBC) is a rare, aggressive breast cancer diagnosed clinically by the presence of diffuse erythema, peau d'orange, and edema that arise quickly in the affected breast. This study evaluated the validity of medical records in Gharbiah, Egypt in identifying clinical signs/symptoms of IBC. For 34 IBC cases enrolled in a case-control study at the Gharbiah Cancer Society and Tanta Cancer Center, Egypt (2009-2010), we compared signs/symptoms of IBC noted in medical records to those recorded on a standardized form at the time of IBC diagnosis by clinicians participating in the case-control study. We calculated the sensitivity …

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 …

Anaesthesia Error In United States: Reasons For Mismanagement, Abby Wolfe, Anh Nguyen, Ashleigh Galles, Madison Wolfe, Ben Lundberg

Posters and Presentations: College of Public Health

A poster from the UNMC Undergraduate Public Health Workshop

Prospecting For An Hiv Vaccine, David Brett-Major, T. A. Crowell, N. L. Michael

Journal Articles: Epidemiology

Human immunodeficiency virus (HIV) sets several challenges for the development of a preventative HIV vaccine. Predictable, protective natural immunity against HIV does not occur and so unlike most other diseases for which vaccines exist, there are few guideposts from natural infection. Nonetheless, six vaccine efficacy trials have occurred. One in particular, the Thai trial called RV144, showed partial protective efficacy and potential ways ahead to a better vaccine approach. This coupled with other lessons from studies of acute infections as well as an increasingly complex knowledge of HIV-related vaccine immunology bring hope that a vaccine solution might be reached for …

Impact Of Simultaneous Exposure To Arboviruses On Infection And Transmission By Aedes Aegypti Mosquitoes, Claudia Rückert, James Weger-Lucarelli, Selene M. Garcia-Luna, Michael C. Young, Alex D. Byas, Reyes A. Murrieta, Joseph R. Fauver, Gregory D. Ebel

Journal Articles: Epidemiology

The recent emergence of both chikungunya and Zika viruses in the Americas has significantly expanded their distribution and has thus increased the possibility that individuals may become infected by more than one Aedes aegypti-borne virus at a time. Recent clinical data support an increase in the frequency of coinfection in human patients, raising the likelihood that mosquitoes could be exposed to multiple arboviruses during one feeding episode. The impact of coinfection on the ability of relevant vector species to transmit any of these viruses (that is, their vector competence) has not been determined. Thus, we here expose Ae. aegypti mosquitoes …

Network-Based Analysis Reveals Novel Gene Signatures In Peripheral Blood Of Patients With Chronic Obstructive Pulmonary Disease, Ma'en Obeidat, Yunlong Nie, Virginia Chen, Casey P. Shannon, Anand Kumar Andiappan, Bernett Lee, Olaf Rotzschke, Peter J. Castaldi, Craig P. Hersh, Nick Fishbane, Raymond T. Ng, Bruce Mcmanus, Bruce E. Miller, Stephen I. Rennard, Peter D. Paré, Don D. Sin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death and there is a huge unmet clinical need to identify disease biomarkers in peripheral blood. Compared to gene level differential expression approaches to identify gene signatures, network analyses provide a biologically intuitive approach which leverages the co-expression patterns in the transcriptome to identify modules of co-expressed genes.

METHODS: A weighted gene co-expression network analysis (WGCNA) was applied to peripheral blood transcriptome from 238 COPD subjects to discover co-expressed gene modules. We then determined the relationship between these modules and forced expiratory volume in 1 s (FEV …

Hpv Vaccination And Knowledge Of Cervical Cancer Among Female University Students In A Multiethnic Institution, Usa, Nasar U. Ahmed, Michael E. Delgado, Abraham Degarege

Journal Articles: Epidemiology

Objective: College-aged women are at high-risk of Human Papillomavirus (HPV) infection. Although, HPV vaccination is most effective, its rates remain quite low among college students. It may be due to inadequate understanding of the relationship between HPV and cervical cancer. Therefore, the objective of this study was to examine the level of knowledge about HPV, cervical cancer and their associations with HPV vaccination among female college students.

Methods: Cross-sectional questionnaire based survey was conducted among female students in a Multiethnic University in Florida. We assessed HPV vaccination status, annual health checkup status, knowledge about HPV and cervical cancer among the …

Without The White Coat: An Analysis Of Pathographies By Physicians With Cancer, Jonathan H. Ryder

EMET Projects

No abstract provided.

Ultrasound-Induced Microbubble Cavitation For The Treatment Of Catheterization-Induced Vasospasm, Shelby Kutty, Na Liu, Jia Zhou, Yunbin Xiao, Juefei Wu, David A. Danford, John Lof, Feng Xie, Thomas R. Porter

Journal Articles: Pediatrics

No abstract provided.

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.

Randomized Trial Of Two Doses Of Vitamin D3 In Preterm Infants <32 Weeks: Dose Impact On Achieving Desired Serum 25(Oh)D3 In A Nicu Population., Ann Anderson-Berry, Melissa Thoene, Julie Wagner, Elizabeth Lyden, Glenville Jones, Martin Kaufmann, Matthew Van Ormer, Corrine K. Hanson

Journal Articles: Pediatrics

BACKGROUND: Recommendations for vitamin D supplementation for preterm infants span a wide range of doses. Response to vitamin D supplementation and impact on outcomes in preterm infants is not well understood.

OBJECTIVE: Evaluate serum 25(OH)D3 concentration changes after 4 weeks in response to two different doses of vitamin D3 supplementation in a population of premature infants and quantify the impact on NICU outcomes.

DESIGN: 32 infants born at 24-32 weeks gestation were prospectively randomized to receive 400 or 800 IU/day vitamin D3 supplementation. Serum 25(OH)D3 levels were measured every 4 weeks. The Wilcoxon signed rank test was used to compare …

Geographical Analysis Of Sudden Infant Death Syndrome (Sids) And Associated Risk Factors In Douglas County, Nebraska, Caitlin E. Fee, Ariel Tarrell

EMET Projects

Background: Sudden Infant Death Syndrome (SIDS) is defined as the sudden and unexpected death of a child less than one year of age without an identifiable cause. Known risk factors of SIDS include prone and side-sleeping positions, bed sharing, male sex, pre- and postnatal tobacco exposure, poverty, prematurity, low birth weight (1

Significance of Problem: In the United States, SIDS is the most common cause of death in infants between one month and one year of age with approximately 2,500 infant deaths caused by SIDS each year.¹ The incidence of SIDS has decreased by more than 50% in the …

Multifaceted Role Of Neuropilins In The Immune System: Potential Targets For Immunotherapy., Sohini Roy, Arup K. Bag, Rakesh Singh, James E. Talmadge, Surinder K. Batra, Kaustubh Datta

Journal Articles: Biochemistry & Molecular Biology

Neuropilins (NRPs) are non-tyrosine kinase cell surface glycoproteins expressed in all vertebrates and widely conserved across species. The two isoforms, such as neuropilin-1 (NRP1) and neuropilin-2 (NRP2), mainly act as coreceptors for class III Semaphorins and for members of the vascular endothelial growth factor family of molecules and are widely known for their role in a wide array of physiological processes, such as cardiovascular, neuronal development and patterning, angiogenesis, lymphangiogenesis, as well as various clinical disorders. Intriguingly, additional roles for NRPs occur with myeloid and lymphoid cells, in normal physiological as well as different pathological conditions, including cancer, immunological disorders, …

Articles For The Student Forum, Edward F. Rossomando, Jafar Kolahi, Francesco Chippelli, David G. Dunning, Heejung Bang, Saber Khazaei, Luca Giacomelli, Gunnar Hasselgren, Vuokko Anttonen

Journal Articles: College of Dentistry

No abstract provided.

Chemosensitization Effect Of Sp1017 On Multiple Myeloma, Hangting Hu

Theses & Dissertations

Multiple myeloma (MM) is a hematological malignancy of plasma cells that are predominantly located in bone marrow (BM). Despite recent improvements in MM treatment by introduction of several novel agents includingimmunomodulatory drugs, proteasome inhibitors and the use of the drug combinations, MM remains incurable and almost all patients eventually relapse or become refractory to the current treatment regimens. So the current challenge of MM treatments is to maintain treatment response, prevent relapse and eventually prolong survival.

Here we demonstrated that Pluronic block copolymers ((Pluronic L61: Pluronic F127 = 1:8 w/w, SP1017) significantly increase cytotoxicity of proteasome inhibitors (Bortezomib, BTZ or …

Target Validation And Pharmacological Characterization Of Novel Nmdar Modulators, Kiran Sapkota

Theses & Dissertations

The N-methyl-D aspartate receptors (NMDARs) are ligand-gated ion channels, which play important roles in learning and memory. Excessive activity of NMDARs is implicated in damage due to stroke and neurodegenerative diseases, whereas hypoactivity of NMDARs contributes to schizophrenia. The initial goal of my dissertation is to evaluate the potential role of the GluN2D-containing NMDARs in neuropathological, behavioral and cognitive alterations associated with schizophrenia and characterize the pharmacology and mechanisms of action of NMDAR modulators which could potentially be used to modulate these receptors in schizophrenia.

A subanesthetic dose of the NMDAR antagonist ketamine elicits symptoms of schizophrenia. This property led …

Polymeric Nanocarriers For Delivery Of Small Molecules And Mirnas For The Treatment Of Liver Fibrosis And Pancreatic Cancer, Virender Kumar

Theses & Dissertations

The aim of this thesis is to develop combination therapy of small molecules and miRNAs for treating liver fibrosis and pancreatic cancer. New amphiphilic biodegradable polymers capable of carrying small hydrophobic molecules and hydrophilic anionic nucleic acids were synthesized, characterized and evaluated in vitro and in vivo liver fibrosis and pancreatic cancer mouse models.

In Chapter 1, an overview of liver fibrosis, current treatments and the role of miRNAs in liver fibrosis as well as the design of their delivery systems is given. Further, a general introduction to pancreatic cancer and role of miRNAs in pancreatic cancer is given. In …

Development Of Cxcr4-Inhibiting Nanoparticles For The Treatment Of Metastatic Cancer, Yan Wang

Theses & Dissertations

Metastasis is the main cause of cancer mortality and morbidity, leading to several million deaths every year. Less than 20% of pancreatic cancer (PC) patients are candidates for surgery due to spread beyond the pancreas. Desmoplasia presents substantial barriers to perfusion, diffusion, and convection of antitumor therapeutics into the PC tissues. We focus on developing novel therapies that regulates tumor microenvironment, chemosensitizing tumor to therapeutics and preventing metastasis.

Gene therapy is emerging as a promising new therapeutic agents for cancer treatment. A targeted, systemic, effective and safe gene delivery system should be developed. CXCR4/SDF-1 axis plays a crucial role in …

Effects Of Flash-Free Technique On Plaque Retention, White Spot Lesions, And Bracket Failure: A Randomized Clinical Trial, Payam Ishani Afousi

Theses & Dissertations

A side effect of orthodontic treatment is the development of white spot lesions (WSLs). This thesis attempted to evaluate the effects of the use of APC™ Flash-Free (FF) and conventional adhesives in bonding of orthodontic brackets on plaque formation and retention, WSL development, and bracket failure in-vivo. This was accomplished by collecting plaque samples from around orthodontic appliances and analyzing them using ATP-driven bioluminescence; scanning enamel surfaces using the Canary System™ to evaluate WSL development, and counting the number of spontaneous debonding of brackets of the 4 maxillary incisors in the first 6 months of treatment. It was found …

Bone Loss Quantification Following Extraction In Rats: A Foundation For Grafting And Regenerative Studies, Emily Willett

Theses & Dissertations

Background: Loss of the alveolar ridge width and height following extraction is well-documented and several techniques, including grafting, have been proposed to reduce bone loss. Purpose: To characterize the pattern of bone turnover and inflammation after extraction and to initiate a study of the effect of grafting and local administration of simvastatin (SIM). Methods: Thirty-two retired-breeder rats underwent extraction of the right maxillary first molar and standard surgical defect creation under inhalation anesthesia. The left side of each animal served as the unmanipulated control. Comparison of groups (n=8, ANOVA) was done at days 0, 7, 14, and …

Design, Synthesis, And Evaluation Of Aryl Hydantoins And Ureas As Antischistosomal Agents, Chunkai Wang

Theses & Dissertations

Schistosomiasis is a tropical parasitic disease caused by infections with flukes of the genus Schistosoma, affecting as many as 440 million individuals worldwide, with 779 million living at risk of infection. A new drug for schistosomiasis is urgently needed as praziquantel (PZQ) is currently the drug of last resort and the development of resistance cannot be ignored, particularly in view of its large-scale use in many endemic countries. Furthermore, PZQ is active against adult but not juvenile schistosomes; this may be an important factor in the frequently observed treatment ‘failures’ in areas endemic for schistosomiasis.

The introduction of PZQ in …