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Mir-133a Mimic Alleviates T1dm-Induced Systolic Dysfunction In Akita: An Mri-Based Study, Shyam S. Nandi, Hamid R. Shahshahan, Quanliang Shang, Shelby Kutty, Michael D. Boska, Paras K. Mishra

Journal Articles: Pediatrics

Diabetic cardiomyopathy is a leading cause of heart failure. Developing a novel therapeutic strategy for diabetic cardiomyopathy and characterizing animal models used for diabetes mellitus (DM) are important. Insulin 2 mutant (Ins2^+/-) Akita is a spontaneous, genetic, mouse model for T1DM, which is relevant to humans. There are contrasting reports on systolic dysfunction and pathological remodeling (hypertrophy and fibrosis) in Akita heart. Here, we used magnetic resonance imaging (MRI) approach, a gold standard reference for evaluating cardiac function, to measure ejection fraction (indicator of systolic dysfunction) in Akita. Moreover, we performed Wheat Germ Agglutinin (WGA) and hematoxylin and …

Ecg Findings In Pediatric Patients Under The Influence Of Marijuana, Jeffrey A. Robinson, Sahana Somasegar, Jill K. Shivapour, Christopher S. Snyder

Journal Articles: Pediatrics

Background: The effects of marijuana on the cardiac conduction system are ill defined. The purpose of this study is to describe the association between electrocardiogram (ECG) findings and positive urine drug screening (+UDS) for marijuana in the pediatric population. Methods: A retrospective review was conducted through the electronic medical record from Emergency Department (ED) visits dated 10/13- 11/14 of patients ≤ 18 years of age who tested positive for marijuana exposure by +UDS in the ED. Inclusion criteria included: 1) +UDS for marijuana performed in the ED and 2) electrocardiogram (ECG) performed on same day as +UDS. Each ECG was …

Atrioventricular Junctional Tachycardia With Exit Block In An Adolescent, Nicholas M. Cundiff, Jeffrey A. Robinson, Bryan C. Cannon, Christopher S. Snyder

Journal Articles: Pediatrics

No abstract provided.

Improved Therapy For Medulloblastoma: Targeting Hedgehog And Pi3k-Mtor Signaling Pathways In Combination With Chemotherapy, Nagendra K. Chaturvedi, Matthew J. Kling, Don W. Coulter, Timothy R. Mcguire, Sutapa Ray, Varun Kesherwani, Shantaram S. Joshi, J. Graham Sharp

Journal Articles: Radiation Oncology

Aberrant activation and interactions of hedgehog (HH) and PI3K/AKT/mTOR signaling pathways are frequently associated with high-risk medulloblastoma (MB). Thus, combined targeting of the HH and PI3K/AKT/mTOR pathways could be a viable therapeutic strategy to treat high-risk patients. Therefore, we investigated the anti-MB efficacies of combined HH inhibitor Vismodegib and PI3K-mTOR dual-inhibitor BEZ235 together or combined individually with cisplatin against high-risk MB. Using non-MYC- and MYC-amplified cell lines, and a xenograft mouse model, the in vitro and in vivo efficacies of these therapies on cell growth/survival and associated molecular mechanism(s) were investigated. Results showed that combined treatment of Vismodegib and BEZ235 …

A Pharmacist-Led Medication Switch Protocol In An Academic Hiv Clinic: Patient Knowledge And Satisfaction, Sarah S. Lee, Joshua P. Havens, Harlan R. Sayles, Jennifer L. O'Neill, Anthony T. Podany, Susan Swindells, Kimberly K. Scarsi, Sara H. Bares

Journal Articles: Infectious Diseases

BACKGROUND: Tenofovir alafenamide (TAF) is associated with less renal and bone toxicity compared with tenofovir disoproxil (TDF). TAF's recent FDA approval has spurred HIV providers to consider switching antiretroviral therapy (ART) regimens containing TDF to TAF to minimize long term risks. Patient views on the process of such medication switches have not been explored.

METHODS: Patients taking elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) following the Food and Drug Administration's (FDA) approval of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) received medication education from an HIV pharmacist prior to switching to the tenofovir alafenamide (TAF) formulation. Patients were asked to complete a cross-sectional survey assessing satisfaction with …

Determinants Of Facilitated Health Insurance Enrollment For Patients With Hiv Disease, And Impact Of Insurance Enrollment On Targeted Health Outcomes., Renae Furl, Shinobu Watanabe-Galloway, Elizabeth Lyden, Susan Swindells

Journal Articles: Infectious Diseases

BACKGROUND: The introduction of the Affordable Care Act (ACA) has provided unprecedented opportunities for uninsured people with HIV infection to access health insurance, and to examine the impact of this change in access. AIDS Drug Assistance Programs (ADAPs) have been directed to pursue uninsured individuals to enroll in the ACA as both a cost-saving strategy and to increase patient access to care. We evaluated the impact of ADAP-facilitated health insurance enrollment on health outcomes, and demographic and clinical factors that influenced whether or not eligible patients enrolled.

METHODS: During the inaugural open enrollment period for the ACA, 284 Nebraska ADAP …

Abnormal T Cell Frequencies, Including Cytomegalovirus-Associated Expansions, Distinguish Seroconverted Subjects At Risk For Type 1 Diabetes, Robert Z. Harms, Kristina M. Lorenzo-Arteaga, Katie R. Ostlund, Victoria B. Smith, Lynette M. Smith, Peter Gottlieb, Nora Sarvetnick

Journal Articles: Surgery

We analyzed T cell subsets from cryopreserved PBMC obtained from the TrialNet Pathway to Prevention archives. We compared subjects who had previously seroconverted for one or more autoantibodies with non-seroconverted, autoantibody negative individuals. We observed a reduced frequency of MAIT cells among seroconverted subjects. Seroconverted subjects also possessed decreased frequencies of CCR4-expressing CD4 T cells, including a regulatory-like subset. Interestingly, we found an elevation of CD57+, CD28-, CD127-, CD27- CD8 T cells (SLEC) among seroconverted subjects that was most pronounced among those that progressed to disease. The frequency of these SLEC was strongly correlated with CMV IgG abundance among seroconverted …

Selective Infarct Zone Imaging With Intravenous Acoustically Activated Droplets, Songita A. Choudhury, Feng Xie, Shelby Kutty, John Lof, Elizabeth Stolze, Thomas R. Porter

Journal Articles: Pediatrics

BACKGROUND: Microbubbles (MB) can be compressed to nanometer-sized droplets and reactivated with diagnostic ultrasound; these reactivated MB possess unique imaging characteristics.

OBJECTIVE: We hypothesized that droplets formed from compressing Definity MB may be used for infarct-enhancement imaging.

METHODS: Fourteen rats underwent ligation of their left anterior descending (LAD) artery, and five pigs underwent 90 minute balloon occlusions of their mid LAD. At 48 hours in rats, transthoracic ultrasound was performed at two and four minutes following 200 μL intravenous injections (IVI) of Definity droplets (DD), at which point the MI was increased from 0.5 to 1.5 to assess for a …

Aminoglycosides Rapidly Inhibit Nad(P)H Metabolism Increasing Reactive Oxygen Species And Cochlear Cell Demise, Danielle E. Desa, Michael G. Nichols, Heather Jensen Smith

Journal Articles: Eppley Institute

Despite causing permanent hearing loss by damaging inner ear sensory cells, aminoglycosides (AGs) remain one of the most widely used classes of antibiotics in the world. Although the mechanisms of cochlear sensory cell damage are not fully known, reactive oxygen species (ROS) are clearly implicated. Mitochondrial-specific ROS formation was evaluated in acutely cultured murine cochlear explants exposed to gentamicin (GM), a representative ototoxic AG antibiotic. Superoxide (O2·-) and hydrogen peroxide (H2O2) were measured using MitoSOX Red and Dihydrorhodamine 123, respectively, in sensory and supporting cells. A 1-h GM exposure significantly increased O2·- formation in IHCs and increased H2O2 formation in …

Short Term Dynamics Of The Sputum Microbiome Among Copd Patients., Rohita Sinha, Lisa A. Weissenburger-Moser, Jennifer L. Clarke, Lynette M. Smith, Art J. Heires, Debra J. Romberger, Tricia D. Levan

Journal Articles: Internal Medicine

Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder characterized by incompletely reversible airflow obstruction. The complexity of the lung microbial community in COPD patients has been highlighted in recent years. Evidence suggests that transplantation, medications, age, and disease severity influence microbial community membership. However, the dynamics of the lung microbiome in stable COPD patients remain poorly understood. In this study, we completed a longitudinal 16S ribosomal RNA survey of the lung microbiome on replicate sputum samples collected from 4 former smokers with COPD (Stage 2) within a 2-day time period. Samples from each individual over the two-day period were …

Midwest Pharmacists' Familiarity, Experience, And Willingness To Provide Pre-Exposure Prophylaxis (Prep) For Hiv, Jordan M. Broekhuis, Kimberly K. Scarsi, Harlan R. Sayles, Donald G. Klepser, Joshua P. Havens, Susan Swindells, Sara H. Bares

Journal Articles: Internal Medicine

INTRODUCTION: Pharmacist provision of pre-exposure prophylaxis (PrEP) through collaborative practice agreements with physicians could expand access to people at risk for HIV. We characterized pharmacists' familiarity with and willingness to provide PrEP services in Nebraska and Iowa.

METHODS: An invitation to complete an 18-question survey was emailed to 1,140 pharmacists in Nebraska and Iowa in June and July of 2016. Descriptive analyses and Pearson chi-square tests were used to determine to what extent demographics, familiarity and experience were associated with respondent willingness to provide PrEP. Wilcoxon rank-sum tests compared ages and years of experience between groups of respondents.

RESULTS: One …

Relationship Of Systemic Il-10 Levels With Proinflammatory Cytokine Responsiveness And Lung Function In Agriculture Workers, Tricia D. Levan, Debra J. Romberger, Mohammad Siahpush, Brandon L. Grimm, Athena K. Ramos, Patrik L. Johansson, Tzeyu L. Michaud, Art J. Heires, Todd A. Wyatt, Jill A. Poole

Journal Articles: Internal Medicine

BACKGROUND: Agriculture workers are exposed to microbial component- and particulate matter-enriched organic dust aerosols. Whereas it is clear that exposure to these aerosols can lead to lung inflammation, it is not known how inflammatory responses are resolved in some individuals while others develop chronic lung disease. Interleukin (IL)-10 is an immunomodulatory cytokine that is recognized as a potent anti-inflammatory and pro-resolving factor. The objective of this study was to determine whether there is a relationship of systemic IL-10 and proinflammatory responses and/or respiratory health effects in humans with prior agriculture exposure.

METHODS: This is a cross sectional study of 625 …

Elevated Pressure Increases Ca2+ Influx Through Ampa Receptors In Select Populations Of Retinal Ganglion Cells, Xiangyi Wen, Asia L. Cahill, Cody Barta, Wallace B. Thoreson, Scott Nawy

Journal Articles: Ophthalmology

The predominate type of AMPA receptor expressed in the CNS is impermeable to Ca²⁺ (CI-AMPAR). However, some AMPA receptors are permeable to Ca²⁺ (CP-AMPAR) and play important roles in development, plasticity and disease. In the retina, ganglion cells (RGCs) are targets of disease including glaucoma and diabetic retinopathy, but there are many types of RGCs and not all types are targeted equally. In the present study, we sought to determine if there are differences in expression of AMPARs amongst RGC subtypes, and if these differences might contribute to differential vulnerability in a model of stress. Using cultured RGCs …

Inter-Vendor Reproducibility Of Left And Right Ventricular Cardiovascular Magnetic Resonance Myocardial Feature-Tracking, Roman Johannes Gertz, Torben Lange, Johannes Tammo Kowallick, Sören Jan Backhaus, Michael Steinmetz, Wieland Staab, Shelby Kutty, Gerd Hasenfuß, Joachim Lotz, Andreas Schuster

Journal Articles: Cardiology

AIM: Since cardiovascular magnetic resonance feature-tracking (CMR-FT) has been demonstrated to be of incremental clinical merit we investigated the interchangeability of global left and right ventricular strain parameters between different CMR-FT software solutions.

MATERIAL AND METHODS: CMR-cine images of 10 patients without significant reduction in LVEF and RVEF and 10 patients with a significantly impaired systolic function were analyzed using two different types of FT-software (TomTec, Germany; QStrain, Netherlands). Global longitudinal strains (LV GLS, RV GLS), global left ventricular circumferential (GCS) and radial strains (GRS) were assessed. Differences in intra- and inter-observer variability within and between software types based on …

Microscale Gene Expression Analysis Of Tumor-Associated Macrophages, Kuldeep S. Attri, Kamiya Mehla, Surendra K. Shukla, Pankaj K. Singh

Journal Articles: Eppley Institute

Macrophages, apart from being the key effector cells of the innate immune system, also play critical roles during the development and progression of various complex diseases, including cancer. Tumor-associated macrophages, infiltrate tumors during different stages of cancer progression to regulate motility, invasion, and intravasation to metastatic sites. Macrophages can exist in different polarization states associated with unique function in tumors. Since tumor-associated macrophages constitute a very small proportion of tumor cells, analysis of gene expression pattern using normal extraction buffer-based methods remains a challenging task. Therefore, it is imperative to develop low-throughput strategies to investigate transcriptional regulations from a small …

Phosphoinositide 3-Kinase Signaling Pathway In Pancreatic Ductal Adenocarcinoma Progression, Pathogenesis, And Therapeutics, Divya Murthy, Kuldeep S. Attri, Pankaj K. Singh

Journal Articles: Eppley Institute

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by its sudden manifestation, rapid progression, poor prognosis, and limited therapeutic options. Genetic alterations in key signaling pathways found in early pancreatic lesions are pivotal for the development and progression of pancreatic intraepithelial neoplastic lesions into invasive carcinomas. More than 90% of PDAC tumors harbor driver mutations in K-Ras that activate various downstream effector-signaling pathways, including the phosphoinositide-3-kinase (PI3K) pathway. The PI3K pathway also responds to stimuli from various growth factor receptors present on the cancer cell surface that, in turn, modulate downstream signaling cascades. Thus, the inositide signaling acts …

Met Receptor Inhibitor Su11274 Localizes In The Endoplasmic Reticulum, Edwin J. Wiest, Heather Jensen Smith, Michael A. Hollingsworth

Journal Articles: Eppley Institute

We discovered that SU11274, a class I c-Met inhibitor, fluoresces when excited by 488 nm laser light and showed rapid specific accumulation in distinct subcellular compartments. Given that SU11274 reduces cancer cell viability, we exploited these newly identified spectral properties to determine SU11274 intracellular distribution and accumulation in human pancreatic cancer cells. The aim of the studies reported here was to identify organelle(s) to which SU11274 is trafficked. We conclude that SU11274 rapidly and predominantly accumulates in the endoplasmic reticulum.

Oligomerization Of Bacterially Expressed H1n1 Recombinant Hemagglutinin Contributes To Protection Against Viral Challenge, Tess E. Kuenstling, Anthony R. Sambol, Steven H. Hinrichs, Marilynn A. Larson

Journal Articles: Pathology and Microbiology

Vaccination is the most effective intervention to prevent influenza and control the spread of the virus. Alternatives are needed to the traditional egg-based vaccine strategy for a more rapid response to new outbreaks. Two different hemagglutinin (HA) fragments (rHA1_1-326 and rHA1_53-269) derived from influenza A virus subtype H1N1 were expressed in Escherichia coli and characterized by immunoblot, gel filtration, hemagglutination, and competitive binding assays. rHA1_1-326 included neutralizing epitopes and the trimerization domain, whereas rHA1_53-269 included only the head of HA with the neutralizing epitopes. Mice were immunized with rHA1_1-326 or rHA1_53-269, and …

Searching For Novel Biomarkers Using A Mouse Model Of Cln3-Batten Disease, Derek Timm, Jacob T. Cain, Ryan D. Geraets, Katherine A. White, Seung Yon Koh, Tammy Kielian, David A. Pearce, Michelle L. Hastings, Jill M. Weimer

Journal Articles: Pathology and Microbiology

CLN3-Batten disease is a rare, autosomal recessive disorder involving seizures, visual, motor and cognitive decline, and premature death. The Cln3Δex7/8 mouse model recapitulates several phenotypic characteristics of the most common 1.02kb disease-associated deletion. Identification of reproducible biomarker(s) to facilitate longitudinal monitoring of disease progression and provide readouts for therapeutic response has remained elusive. One factor that has complicated the identification of suitable biomarkers in this mouse model has been that variations in animal husbandry appear to significantly influence readouts. In the current study, we cross-compared a number of biological parameters in blood from Cln3Δex7/8 mice and control, non-disease mice on …

Depressed Left And Right Ventricular Cardiac Output In Fetuses Of Diabetic Mothers, Jennifer Winter, Aparna Kulkarni, Mary Craft, Ling Li, Lisa K. Hornberger, David A. Danford, Shelby Kutty

Journal Articles: Pediatrics

INTRODUCTION: We compared right and left ventricular cardiac output (RVCO and LVCO) in fetuses of diabetic mothers (FDM) to a large normal cohort.

METHODS: We prospectively enrolled 264 normal fetuses and 30 FDM. Fetal CO parameters: semilunar valve velocity time integrals (AVVTI, PVVTI), ventricular outflow diameters (LVOTD, RVOTD), stroke volumes (AVSV, PVSV) were measured, and LVCO and RVCO calculated. These were normalized using nonlinear regression to estimated fetal weight (EFW) to provide means and standard deviations. Among FDMs, mean Z-scores and 95% confidence limits (CL) were calculated, and compared to zero.

RESULTS: LVCO, RVCO, and parameters they were calculated from, …