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Cushing’S Storm Secondary To Ectopic Acth Secreting Metastatic Breast Cancer, Maura Bucciarelli Do, Ya-Yu Lee Md, Vasudev G. Magaji Md, Ms

Department of Medicine

No abstract provided.

The Role Of Glutamate Signalling In Diabetic Neuropathy, Nadia Hussain

Dissertations

The majority of diabetics develop neuropathy, which can be debilitating, but the underlying pathophysiological mechanisms are poorly understood. Diabetic neuropathy progresses in a distal to proximal manner. Previous studies have shown that glutamate, the most common excitatory neurotransmitter, plays a role in the pathogenesis of neuropathy. The reason why the role of glutamate in nociception becomes a problem in diabetes and the mechanisms that are involved are unknown. Based on the preliminary data, the hypothesis was that glutamate pathways are likely to be involved in diabetic neuropathy particularly neuropathic pain. Pathways were investigated to look for changes that might reflect …

Development And Evaluation Of An Opioid Monitoring Clinic, Richard Luna Talusan

UNLV Theses, Dissertations, Professional Papers, and Capstones

An APRN-led Opioid Monitoring Clinic was developed and implemented in the primary care setting of Las Vegas' Department of Veterans Affairs in July 2013 to assist primary care providers (PCP) in the management of high risk patients on chronic opioid

therapy for chronic noncancer pain. The clinic assisted in monitoring patients for abuse and misuse of opioids and referred patients for treatment when abuse and misuse were discovered. A study to evaluate the OMC was undertaken from November 22, 2013

through February 23, 2014 to assess the effectiveness of the OMC in meeting its objectives. A total of 61 patients …

Analysis Of Ligand Bias In Functional Studies Involving The Allosteric Modulation Of G Protein- Coupled Receptors, Frederick J. Ehlert, Michael T. Griffin

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Introduction

The affinity constants of a ligand for active and inactive states of a receptor ultimately determine its capacity to activate downstream signaling events. In this report, we describe a reverse-engineering strategy for estimating these microscopic constants.

Methods

Our approach involves analyzing responses measured downstream in the signaling pathway of a G protein-coupled receptor under conditions of allosteric modulation and reduced receptor expression or partial receptor inactivation. The analysis also yields estimates of the isomerization constant of the unoccupied receptor, the sensitivity constant of the signaling pathway, and the more empirical parameters of the receptor population including the observed affinities …

Measuring The Effects Of Ctrp3 And Metformin On H4iie Hepatocyte Metabolism Using Seahorse Extracellular Flux Analyzer, Forrest J. Longway

Undergraduate Honors Theses

Non-alcoholic fatty liver disease (NAFLD) results from an unequal uptake/storage and export/oxidation of lipids within the liver and is often a secondary disease to type II diabetes (22). NAFLD causes this imbalance of lipids by altering glucose and lipid metabolism, which corresponds to a decrease in mitochondrial function leading to failure of the liver. One established treatment for type II diabetes and NAFLD is the drug metformin, which has similar properties to the newly discovered CTRP 3 protein which is part of a group of bioactive molecules secreted by adipose tissue, collectively termed adipokines (2-4). Both have similar effects on …

Predicting Targeted Drug Combinations Based On Pareto Optimal Patterns Of Coexpression Network Connectivity, Nadia M. Penrod, Casey S. Greene, Jason H. Moore

Dartmouth Scholarship

Molecularly targeted drugs promise a safer and more effective treatment modality than conventional chemotherapy for cancer patients. However, tumors are dynamic systems that readily adapt to these agents activating alternative survival pathways as they evolve resistant phenotypes. Combination therapies can overcome resistance but finding the optimal combinations efficiently presents a formidable challenge. Here we introduce a new paradigm for the design of combination therapy treatment strategies that exploits the tumor adaptive process to identify context-dependent essential genes as druggable targets. We have developed a framework to mine high-throughput transcriptomic data, based on differential coexpression and Pareto optimization, to investigate drug-induced …

Suppression Of Basophil Histamine-Release And Other Ige-Dependent Responses In Childhood Schistosoma Mansoni Hookworm Co-Infection, Angela Pinot De Moira, Colin M. Fitzsimmons, Frances M. Jones, Shona Wilson, Pierre Cahen, Edridah Tukahebwa, Harriet Mpairwe, Joseph K. Mwatha, Jeffrey M. Bethony, Per S. Skov, Narcis B. Kabatereine, David W. Dunne

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background. The poor correlation between allergen-specific-IgE (asIgE) and clinical signs of allergy in helminth infected populations suggests that helminth infections could protect against allergy by uncoupling asIgE from its effector mechanisms. We investigated this hypothesis in Ugandan schoolchildren coinfected with Schistosoma mansoni and hookworm.

Methods. Skin prick test (SPT) sensitivity to house dust mite allergen (HDM) and current wheeze were assessed pre-anthelmintic treatment. Non-specific (anti-IgE), helminth-specific and HDM-allergen-specific basophil histamine release (HR), plus helminth- and HDM-specific IgE and IgG4 responses were measured pre- and post-treatment.

Results. Non-specific- and helminth-specific-HR, and associations between helminth-specific-IgE and helminth-specific-HR increased post-treatment. Hookworm infection appeared …

Tumor Microenvironment-Based Feed-Forward Regulation Of Nos2 In Breast Cancer Progression, Julie L. Heinecke, Lisa A. Ridnour, Robert Y.S. Cheng, Christopher H. Switzer, Michael M. Lizardo, Chand Khanna, Sharon A. Glynn, S. Perwez Hussain, Howard A. Young, Stefan Ambs, David A. Wink

United States Public Health Resources

Inflammation is widely recognized as an inducer of cancer progression. The inflammation-associated enzyme, inducible nitric oxide synthase (NOS2), has emerged as a candidate oncogene in estrogen receptor (ER)-negative breast cancer, and its increased expression is associated with disease aggressiveness and poor survival. Although these observations implicate NOS2 as an attractive therapeutic target, the mechanisms of both NOS2 induction in tumors and nitric oxide (NO)-driven cancer progression are not fully understood. To enhance ourmechanistic understanding of NOS2 induction in tumors and its role in tumor biology, we used stimulants of NOS2 expression in ER- and ER+ breast cancer cells and examined …

The Relationship Of Body Mass Index On Primary Care Physician Practice Behaviors With Their Overweight And Obese Patients, Kevin A. Vrablik Md, Mph, Facoem, Judith Green-Mckenzie Md, Mph, Facoem, Steven W. Godin Phd, Mph, Phi Certificate

Department of Medicine

No abstract provided.

Fatty Acids Increase Neuronal Hypertrophy Of Pten Knockdown Neurons, Catherine J. Fricano, Tyrone Despenza, Paul W. Frazel, Meijie Li, A. James O'Malley, Gary Westbrook, Bryan Luikart

Dartmouth Scholarship

Phosphatase and tensin homolog (Pten) catalyzes the reverse reaction of PI3K by dephosphorylating PIP3 to PIP2. This negatively regulates downstream Akt/mTOR/S6 signaling resulting in decreased cellular growth and proliferation. Co-injection of a lentivirus knocking Pten down with a control lentivirus allows us to compare the effects of Pten knockdown between individual neurons within the same animal. We find that knockdown of Pten results in neuronal hypertrophy by 21 days post-injection. This neuronal hypertrophy is correlated with increased p-S6 and p-mTOR in individual neurons. We used this system to test whether an environmental factor that has been implicated in cellular hypertrophy …

The Effect Of Size On Ag Nanosphere Toxicity In Macrophage Cell Models And Lung Epithelial Cell Lines Is Dependent On Particle Dissolution, Raymond F. Hamilton, Sarah Buckingham, Andrij Holian

Biomedical and Pharmaceutical Sciences Faculty Publications

Silver (Ag) nanomaterials are increasingly used in a variety of commercial applications. This study examined the effect of size (20 and 110 nm) and surface stabilization (citrate and PVP coatings) on toxicity, particle uptake and NLRP3 inflammasome activation in a variety of macrophage and epithelial cell lines. The results indicated that smaller Ag (20 nm), regardless of coating, were more toxic in both cell types and most active in the THP-1 macrophages. TEM imaging demonstrated that 20 nm Ag nanospheres dissolved more rapidly than 110 nm Ag nanospheres in acidic phagolysosomes consistent with Ag ion mediated toxicity. In addition, there …

A Comparison Of Clustering And Missing Data Methods For Health Sciences, Ran Zhao, Deanna Needell, Christopher Johansen, Jerry L. Grenard

CMC Faculty Publications and Research

In this paper, we compare and analyze clustering methods with missing data in health behavior research. In particular, we propose and analyze the use of compressive sensing's matrix completion along with spectral clustering to cluster health related data. The empirical tests and real data results show that these methods can outperform standard methods like LPA and FIML, in terms of lower misclassification rates in clustering and better matrix completion performance in missing data problems. According to our examination, a possible explanation of these improvements is that spectral clustering takes advantage of high data dimension and compressive sensing methods utilize the …

Characterization Of The Discriminative Stimulus Effects Of Nitrous Oxide, Kellianne J. Richardson

Theses and Dissertations

Nitrous oxide (N2O) is a widely used anesthetic adjunct in dentistry and medicine that is also commonly abused. N2O alters the function of several receptors in vitro and ex vivo, however, the receptors systems underlying its abuse-related intoxicating effects are poorly understood. The goals of this dissertation were to (1) establish N2O as a discriminative stimulus, (2) characterize the temporal properties of the discriminative stimulus, (3) determine the degree of similarity between N2O and other inhalants and (4) explore the neurochemical effects responsible for the stimulus properties of N2O. Twenty-four mice were trained to discriminate 10 minutes exposure to 60% …

The End Of Alzheimer's Disease - From Biochemical Pharmacology To Ecopsychosociology: A Personal Perspective, Peter J. Whitehouse

Faculty Scholarship

The future of the Alzheimer's disease (AD) field involves a more complete understanding not only the state of current scientific approaches, but also the linguistic and cultural context of preclinical and clinical research and policy activities. The challenges surrounding dementia are large and growing but are only part of broader social and health concerns. In this latter context, the current state of research in the AD area is reviewed together with necessary priorities in moving forward. Creating a more optimistic future will depend less on genetic and reductionist approaches and more on environmental and intergenerative approaches that will aid in …

Proceedings - Wright State University Boonshoft School Of Medicine Sixth Annual Medical Student Research Symposium: Celebrating Medical Student Scholarship, Office Of Research Affairs, Boonshoft School Of Medicine

Medical Student Research Symposium Proceedings

The student abstract booklet is a compilation of abstracts from students' oral and poster presentations at Wright State University's Sixth Annual Boonshoft School of Medicine Medical Student Research Symposium held on April 10, 2014.

An Immunomics Approach To Schistosome Antigen Discovery: Antibody Signatures Of Naturally Resistant And Chronically Infected Individuals From Endemic Areas, Soraya Gaze, Patrick Driguez, Mark S. Pearson, Tiago Mendes, Denise L. Doolan, Jeffrey M. Bethony, +14 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Schistosomiasis is a neglected tropical disease that is responsible for almost 300,000 deaths annually. Mass drug administration (MDA) is used worldwide for the control of schistosomiasis, but chemotherapy fails to prevent reinfection with schistosomes, so MDA alone is not sufficient to eliminate the disease, and a prophylactic vaccine is required. Herein, we take advantage of recent advances in systems biology and longitudinal studies in schistosomiasis endemic areas in Brazil to pilot an immunomics approach to the discovery of schistosomiasis vaccine antigens. We selected mostly surface-derived proteins, produced them using an in vitro rapid translation system and then printed them to …

Common And Specific Impairments In Attention Functioning In Girls With Chromosome 22q11.2 Deletion, Fragile X Or Turner Syndromes., Andrea I Quintero, Elliott A Beaton, Danielle J Harvey, Judith L. Ross, Tony J Simon

Department of Pediatrics Faculty Papers

BACKGROUND: Chromosome 22q11.2 deletion syndrome (22q11.2DS), fragile X syndrome (FXS), and Turner syndrome (TS) are complex and variable developmental syndromes caused by different genetic abnormalities; yet, they share similar cognitive impairments in the domains of numbers, space, and time. The atypical development of foundational neural networks that underpin the attentional system is thought to result in further impairments in higher-order cognitive functions. The current study investigates whether children with similar higher-order cognitive impairments but different genetic disorders also show similar impairments in alerting, orienting, and executive control of attention.

METHODS: Girls with 22q11.2DS, FXS, or TS and typically developing (TD) …

Capping Amyloid Β‑Sheets Of The Tau-Amyloid Structure Vqivyk With Hexapeptides Designed To Arrest Growth. An Oniom And Density Functional Theory Study, Joshua A. Plumley, Jorge Ali-Torres, Gabor Pohl, J. J. Dannenberg

Publications and Research

We present ONIOM calculations using density functional theory (DFT) as the high and AM1 as the medium level that explore the abilities of different hexapeptide sequences to terminate the growth of a model for the tau-amyloid implicated in Alzheimer’s disease. We delineate and explore several design principles (H-bonding in the side chains, using antiparallel interactions on the growing edge of a parallel sheet, using all-D residues to form rippled interactions at the edge of the sheet, and replacing the H-bond donor N−H’s that inhibit further growth) that can be used individually and in combination to design such peptides that will …

Evaluation Of Novel Oral Vaccine Candidates And Validation Of A Caprine Model Of Johne’S Disease, Murray E. Hines Ii, Sue E. Turnquist, Marcia R.S. Ilha, Sreekumari Rajeev, Arthur L. Jones, Lisa Whittington, John P. Bannantine, Raul G. Barletta, Yrjö T. Gröhn, Robab Katani, Adel M. Talaat, Lingling Li, Vivek Kapur

School of Veterinary and Biomedical Sciences: Faculty Publications

Johne’s disease (JD) caused by Mycobacterium avium subspecies paratuberculosis (MAP) is a major threat to the dairy industry and possibly some cases of Crohn’s disease in humans. A MAP vaccine that reduced of clinical disease and/or reduced fecal shedding would aid in the control of JD. The objectives of this study were (1) to evaluate the efficacy of 5 attenuated strains of MAP as vaccine candidates compared to a commercial control vaccine using the protocol proposed by the Johne’s Disease Integrated Program (JDIP) Animal Model Standardization Committee (AMSC), and (2) to validate the AMSC Johne’s disease go at challenge model. …

Celiac Disease As A Model For The Evolution Of Multifactorial Disease In Humans, Aaron Sams, John Hawks

Human Biology Open Access Pre-Prints

Celiac disease (CD) is a multifactorial chronic inflammatory condition that results in injury of the mucosal lining of the small intestine upon ingestion of wheat gluten and related proteins from barley and rye. Although the exact mechanisms leading to CD are not fully understood, the genetic basis of CD has been relatively well characterized. In this review we briefly review the history of discovery, clinical presentation, pathophysiology, and current understanding of the genetics underlying CD risk. Then, we discuss what is known about the current distribution and evolutionary history of genes underlying CD risk in light of other evolutionary models …

Genome Of The Human Hookworm Necator Americanus, Yat T. Tang, Xin Gao, Bruce A. Rosa, Sahar Abubucker, Kymberlie Hallsworth-Pepin, Peter J. Hotez, Jeffrey M. Bethony, +23 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The hookworm Necator americanus is the predominant soil-transmitted human parasite. Adult worms feed on blood in the small intestine, causing iron-deficiency anemia, malnutrition, growth and development stunting in children, and severe morbidity and mortality during pregnancy in women. We report sequencing and assembly of the N. americanus genome (244 Mb, 19,151 genes). Characterization of this first hookworm genome sequence identified genes orchestrating the hookworm's invasion of the human host, genes involved in blood feeding and development, and genes encoding proteins that represent new potential drug targets against hookworms. N. americanus has undergone a considerable and unique expansion of immunomodulator proteins, …

Impact Testing Of Youth-Level Helmets Versus College-Level Helmets, Nicole Hermann

Industrial Technology and Packaging

With so many studies being conducted on professional football players regarding concussions and other related brain injuries, it’s amazing that such an important demographic has been missed. While NFL players are just as subjected to serious injuries as anyone else or even more so, it is important to remember that these players are outfitted, in most cases, with top-of-the-line equipment -- especially their helmets. If the focus is shifted to a younger demographic, youth football players in middle school and high school, the equipment is far less advanced and in a vast majority of cases, has been previously used by …

Deep Rna Sequencing Reveals Hidden Features And Dynamics Of Early Gene Transcription In Paramecium Bursaria Chlorella Virus 1, Guillaume Blanc, Michael Mozar, Irina V. Agarkova, James R. Gurnon, Giane Yanai-Balser, Janet M. Rowe, Yuannan Xia, Jean-Jack Riethoven, David D. Dunigan, James L. Van Etten

Nebraska Center for Virology: Faculty Publications

Paramecium bursaria chlorella virus 1 (PBCV-1) is the prototype of the genus Chlorovirus (family Phycodnaviridae) that infects the unicellular, eukaryotic green alga Chlorella variabilis NC64A. The 331-kb PBCV-1 genome contains 416 major open reading frames. A mRNA-seq approach was used to analyze PBCV-1 transcriptomes at 6 progressive times during the first hour of infection. The alignment of 17 million reads to the PBCV-1 genome allowed the construction of single-base transcriptome maps. Significant transcription was detected for a subset of 50 viral genes as soon as 7 min after infection. By 20 min post infection (p.i.), transcripts were detected for …

Towards A Better Treatment Of Parkinson's Disease, Bradley Darryl Karain

Loma Linda University Electronic Theses, Dissertations & Projects

Current therapies for Parkinson's Disease, the second most common neurodegenerative disorder, do not prevent disease progression, and induce extremely detrimental side-effects. Improving the best current pharmacological therapy, L-DOPA, carries important clinical benefits, partly by reducing the dose-related side-effects which occur after five to ten years of use. Thus the central aim of this proposal is to determine whether low doses of a D2 antagonist may, by selectively blocking the dopamine autoreceptor-mediated feedback inhibition of dopamine neurons, potentiate L-DOPA's effect on individual basal ganglia neurons and its antiparkinsonian effects in Parkinsonian animals. Electrophysiology (extracellular single-cell recording in the globus pallidus) and …

Xiap Antagonist Embelin Inhibited Proliferation Of Cholangiocarcinoma Cells., Cody J. Wehrkamp, Ashley R. Gutwein, Sathish Kumar Natarajan, Mary Anne Phillippi, Justin L. Mott

Journal Articles: Biochemistry & Molecular Biology

Cholangiocarcinoma cells are dependent on antiapoptotic signaling for survival and resistance to death stimuli. Recent mechanistic studies have revealed that increased cellular expression of the E3 ubiquitin-protein ligase X-linked inhibitor of apoptosis (XIAP) impairs TRAIL- and chemotherapy-induced cytotoxicity, promoting survival of cholangiocarcinoma cells. This study was undertaken to determine if pharmacologic antagonism of XIAP protein was sufficient to sensitize cholangiocarcinoma cells to cell death. We employed malignant cholangiocarcinoma cell lines and used embelin to antagonize XIAP protein. Embelin treatment resulted in decreased XIAP protein levels by 8 hours of treatment with maximal effect at 16 hours in KMCH and Mz-ChA-1 …

Complexity Of Interferon-Γ Interactions With Hsv-1, Nancy J. Bigley

Neuroscience, Cell Biology & Physiology Faculty Publications

The intricacies involving the role of interferon-gamma (IFN-γ) in herpesvirus infection and persistence are complex. Herpes simplex virus type 1 (HSV-1) uses a variety of receptors to enter cells and is transported to and from the host cell nucleus over the microtubule railroad via retrograde and anterograde transport. IFN-γ exerts dual but conflicting effects on microtubule organization. IFN-γ stimulates production of suppressors of cytokine signaling 1 and 3 (SOCS1 and SOCS3), which are involved in microtubule stability and are negative regulators of IFN-γ signaling when overexpressed. IFN-γ also interferes with the correct assembly of microtubules causing them to undergo severe …

Hilar Mossy Cells Provide The First Glutamatergic Synapses To Adult-Born Dentate Granule Cells, Jessica H. Chancey, David J. Poulsen, Jacques I. Wadiche, Linda Overstreet-Wadiche

Biomedical and Pharmaceutical Sciences Faculty Publications

Adult-generated granule cells (GCs) in the dentate gyrus must establish synapses with preexisting neurons to participate in network activity. To determine the source of early glutamatergic synapses on newborn GCs in adult mice, we examined synaptic currents at the developmental stage when NMDA receptor-mediated silent synapses are first established. We show that hilar mossy cells provide initial glutamatergic synapses as well as disynaptic GABAergic input to adult-generated dentate GCs.

Anakinra And Related Drugs Targeting Interleukin-1 In The Treatment Of Cryopyrin-Associated Periodic Syndromes, Inessa Bachove, Christopher Chang

Department of Pediatrics Faculty Papers

Anakinra is an interleukin (IL) receptor antagonist that works by blocking the biological activity of IL-1 by competitively inhibiting binding of IL-1 to the type 1 interleukin receptor. IL-1 production is induced in response to inflammatory stimuli and mediates various physiological mechanisms, including inflammation and immunological reactions. Patients with neonatal onset multisystem inflammatory disease (NOMID) produce excess IL-1β, a major proinflammatory cytokine that regulates innate immune responses. Anakinra binds competitively and this results in a rapid reduction in disease severity. NOMID, also known as chronic infantile neurologic, cutaneous, articular syndrome, is the most severe clinical phenotype in the spectrum of …

Intracellular Calcium Stores Drive Slow Non-Ribbon Vesicle Release From Rod Photoreceptors, Minghui Chen, David Križaj, Wallace B. Thoreson

Journal Articles: Pharmacology & Experimental Neuroscience

Rods are capable of greater slow release than cones contributing to overall slower release kinetics. Slow release in rods involves Ca(2+)-induced Ca(2+) release (CICR). By impairing release from ribbons, we found that unlike cones where release occurs entirely at ribbon-style active zones, slow release from rods occurs mostly at ectopic, non-ribbon sites. To investigate the role of CICR in ribbon and non-ribbon release from rods, we used total internal reflection fluorescence microscopy as a tool for visualizing terminals of isolated rods loaded with fluorescent Ca(2+) indicator dyes and synaptic vesicles loaded with dextran-conjugated pH-sensitive rhodamine. We found that rather than …

Direct Control Of Visual Perception With Phase-Specific Modulation Of Posterior Parietal Cortex, Andrew Jaegle, Tony Ro

Publications and Research

We examined the causal relationship between the phase of alpha oscillations (9–12 Hz) and conscious visual perception using rhythmic TMS (rTMS) while simultaneously recording EEG activity. rTMS of posterior parietal cortex at an alpha frequency (10 Hz), but not occipital or sham rTMS, both entrained the phase of subsequent alpha oscillatory activity and produced a phase-dependent change on subsequent visual perception, with lower discrimination accuracy for targets presented at one phase of the alpha oscillatory waveform than for targets presented at the opposite phase. By extrinsically manipulating the phase of alpha before stimulus presentation, we provide direct evidence that the …