Digital Commons Network^™

Human Cord Blood Serum-Derived App Α-Secretase Cleavage Activity Is Mediated By C1 Complement, Ahsan Habib, Darrell Sawmiller, Huayan Hou, Manasa Kanithi, Jun Tian, Jin Zeng, Dan Zi, Zhi-Xu He, Paul R. Sanberg, Jun Tan

Neurosurgery and Brain Repair Faculty Publications

Alzheimer’s Disease (AD) is the leading cause of dementia in the elderly. In healthy individuals, amyloid precursor protein (APP) is cleaved by α-secretase, generating soluble α-amyloid precursor protein (sAPPα), which contributes neuroprotective functions in the neuronal environment. In contrast, in the neurodegenerative environment of AD patients, amyloid-β-peptide (Aβ) of either 40 or 42 residues are generated by increased activity of β- and γ-secretase. These proteins amalgamate in specific regions of the brain, which disrupts neuronal functions and leads to cognitive impairment. Human umbilical cord blood cells (HUCBC) have proven useful as potential immunomodulatory therapies in various models of neurodegenerative diseases, …

Wada Asymmetry In Patients With Drug-Resistant Mesial Temporal Lobe Epilepsy: Implications For Postoperative Neuropsychological Outcomes, Ryan W. Sever, Andrew C. Vivas, Fernando L. Vale, Mike R. Schoenberg

Neurosurgery and Brain Repair Faculty Publications

No abstract provided.

Children’S Oxygen Administration Strategies Trial (Coast): A Randomised Controlled Trial Of High Flow Versus Oxygen Versus Control In African Children With Severe Pneumonia, Kathryn Maitland, Sarah Kiguli, Robert Opoka, Peter Olupot-Olupot, Charles Engoru, Patricia Njuguna, Victor Bandika, Ayub Mpoya, Andrew Bush, Thomas Williams

Paediatrics and Child Health, East Africa

Background: In Africa, the clinical syndrome of pneumonia remains the leading cause of morbidity and mortality in children in the post-neonatal period. This represents a significant burden on in-patient services. The targeted use of oxygen and simple, non-invasive methods of respiratory support may be a highly cost-effective means of improving outcome, but the optimal oxygen saturation threshold that results in benefit and the best strategy for delivery are yet to be tested in adequately powered randomised controlled trials. There is, however, an accumulating literature about the harms of oxygen therapy across a range of acute and emergency situations that …

Nano-Pulse Stimulation Ablates Orthotopic Rat Hepatocellular Carcinoma And Induces Innate And Adaptive Memory Immune Mechanisms That Prevent Recurrence, Brittany P. Lassiter, Siqi Guo, Stephen J. Beebe

Bioelectrics Publications

Nano-pulse stimulation (NPS), previously called nsPEFs, induced a vaccine-like effect after ablation of orthotopic N1-S1 hepatocellular carcinoma (HCC), protecting rats from subsequent challenges with N1-S1 cells. To determine immunity, immune cell phenotypes were analyzed in naïve, treated and protected rats. NPS provides a positive, post-ablation immuno-therapeutic outcome by alleviating immunosuppressive T regulatory cells (Treg) in the tumor microenvironment (TME), allowing dendritic cell influx and inducing dynamic changes in natural killer cells (NKs), NKT-cells and T-lymphocytes in blood, spleen and liver. NPS induced specific increases in NKs and NKT-cells expressing CD8 and activation receptors CD314-NKG2D and CD161 (NK1.1) in the TME …

Nano-Pulse Stimulation For The Treatment Of Pancreatic Cancer And The Changes In Immune Profile, Sigi Guo, Niculina I. Burcus, James Hornef, Yu Jing, Chunqi Jiang, Richard Heller, Stephen J. Beebe

Bioelectrics Publications

A Pancreatic cancer is a notorious malignant neoplasm with an extremely poor prognosis. Current standard of care is rarely effective against late-stage pancreatic cancer. In this study, we assessed nanopulse stimulation (NPS) as a local treatment for pancreatic cancer in a syngeneic mouse Pan02 pancreatic cancer model and characterized corresponding changes in the immune profile. A single NPS treatment either achieved complete tumor regression or prolonged overall survival in animals with partial tumor regression. While this is very encouraging, we also explored if this local ablation effect could also result in immune stimulation, as was observed when NPS led to …

Cgas Drives Noncanonical-Inflammasome Activation In Age-Related Macular Degeneration, Nagaraj Kerur, Shinichi Fukuda, Daipayan Banerjee, Younghee Kim, Dongxu Fu, Ivana Apicella, Akhil Varshney, Reo Yasuma, Benjamin J. Fowler, Elmira Baghdasaryan, Kenneth M. Marion, Xiwen Huang, Tetsuhiro Yasuma, Yoshio Hirano, Vlad Serbulea, Meenakshi Ambati, Vidya L. Ambati, Yuji Kajiwara, Kameshwari Ambati, Shuichiro Hirahara, Ana Bastos-Carvalho, Yuichiro Ogura, Hiroko Terasaki, Tetsuro Oshika, Kyung Bo Kim, David R. Hinton, Norbert Leitinger, John C. Cambier, Joseph D. Buxbaum, M. Cristina Kenney, Bradley D. Gelfand, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

Geographic atrophy is a blinding form of age-related macular degeneration characterized by retinal pigmented epithelium (RPE) death; the RPE also exhibits DICER1 deficiency, resultant accumulation of endogenous Alu-retroelement RNA, and NLRP3-inflammasome activation. How the inflammasome is activated in this untreatable disease is largely unknown. Here we demonstrate that RPE degeneration in human-cell-culture and mouse models is driven by a noncanonical-inflammasome pathway that activates caspase-4 (caspase-11 in mice) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-β production and gasdermin D-dependent interleukin-18 secretion. Decreased DICER1 levels or Alu-RNA accumulation triggers cytosolic escape of mitochondrial DNA, which engages cGAS. Moreover, caspase-4, gasdermin …

The Relationship Between Central Venous Catheter And Post-Operative Complications In Patients Undergoing Hepatic Resection, David C. O'Connor

Theses and Dissertations

The Relationship Between Central Venous Catheter and Post-operative Complications in Patients Undergoing Hepatic Resection

David C. O’Connor, Ph.D., DNAP, CRNA

A dissertation submitted in partial fulfillment of the requirements for the degree of

Doctor of Philosophy at Virginia Commonwealth University

Virginia Commonwealth University, 2018

Dissertation Chair: Clarence J. Biddle, Ph.D., CRNA

Hepatic resection is indicated for primary and secondary malignancies. Use of a low central venous pressure technique is associated with decreased blood loss in these cases. This technique has evolved; central venous catheters and high dose morphine are no longer used, and patients are extubated earlier. The purpose of …

Shared Genetic And Environmental Influences On Fear, Anxiety, Posttraumatic Stress, And Brain Morphometry, Chelsea Sawyers

Theses and Dissertations

Anxiety disorders (ADs) and stress-related disorders are some of the most common psychiatric disorders in the United States. Like other c0mplex psychiatric illness, genetics and neuroimaging research has focused on understanding their underlying neurobiology. Areas within the fear-network play important roles in threat perception, fear conditioning/learning, cognitive processing, and modulation of fear responses including contextual modulation and extinction and have been implicated in ADs as well as stress disorders such as posttraumatic stress disorder (PTSD). The primary gap in the current search for underlying biological mechanisms is in whether biomarkers associated with disorders share genetic influences with the disorders they …

Response And Resistance To Paradox-Breaking Braf Inhibitor In Melanomas, Edward J. Hartsough, Curtis H. Kugel, Michael J. Vido, Adam C. Berger, Timothy J. Purwin, Allison F. Goldberg, Michael A. Davies, Matthew J. Schiewer, Karen E. Knudsen, Gideon Bollag, Andrew E. Aplin

Department of Cancer Biology Faculty Papers

FDA-approved BRAF inhibitors produce high response rates and improve overall survival in patients with BRAF V600E/K-mutant melanoma, but are linked to pathologies associated with paradoxical ERK1/2 activation in wild-type BRAF cells. To overcome this limitation, a next-generation paradox-breaking RAF inhibitor (PLX8394) has been designed. Here, we show that by using a quantitative reporter assay, PLX8394 rapidly suppressed ERK1/2 reporter activity and growth of mutant BRAF melanoma xenografts. Ex vivo treatment of xenografts and use of a patient-derived explant system (PDeX) revealed that PLX8394 suppressed ERK1/2 signaling and elicited apoptosis more effectively than the FDA-approved BRAF inhibitor, vemurafenib. Furthermore, PLX8394 was …

Analytical High-Resolution Electron Microscopy Reveals Organ-Specific Nanoceria Bioprocessing, Uschi M. Graham, Robert A. Yokel, Alan K. Dozier, Lawrence Drummy, Krishnamurthy Mahalingam, Michael T. Tseng, Eileen Birch, Joseph Fernback

Pharmaceutical Sciences Faculty Publications

This is the first utilization of advanced analytical electron microscopy methods, including high-resolution transmission electron microscopy, high-angle annular dark field scanning transmission electron microscopy, electron energy loss spectroscopy, and energy-dispersive X-ray spectroscopy mapping to characterize the organ-specific bioprocessing of a relatively inert nanomaterial (nanoceria). Liver and spleen samples from rats given a single intravenous infusion of nanoceria were obtained after prolonged (90 days) in vivo exposure. These advanced analytical electron microscopy methods were applied to elucidate the organ-specific cellular and subcellular fate of nanoceria after its uptake. Nanoceria is bioprocessed differently in the spleen than in the liver.

Human Chronic Necrotizing Granulomatous Meningoencephalitis: A Novel Case Report, Alexus P. Taddonio, Eric J. Veloso, Kelly J. Baldwin

Touro College of Osteopathic Medicine (Middletown) Publications and Research

Necrotizing and granulomatous meningoencephalitis are common central nervous system diseases known to affect canines. To date, necrotizing granulomatous meningoencephalitis has yet to be described in humans. Current studies of presumed pathogenesis and possible treatment options have only been described in canines. This is a case report of a 55-year-old female patient who was diagnosed with necrotizing granulomatous meningoencephalitis in the setting of new-onset neurological symptoms without any infectious or malignant source.

When Popular Culture And The Nfl Collide: Fan Responsibility In Ending The Concussion Crisis, Taylor Simpson-Wood, Robert H. Wood

Marquette Sports Law Review

None

Non-Naturally Occurring Porcine Reproductive And Respiratory Syndrome Virus (Prrsv) And Methods Of Using, Hiep Lai Xuan Vu, Fernando Osorio, William W. Laegreid, Asit K. Pattnaik, Fangrui Ma

Nebraska Center for Virology: Faculty Publications

A non-naturally occurring porcine reproductive and respiratory syndrome virus (PRRSV) is provided herein, and methods of making and using the non-naturally occurring PRRSV also are provided.

Electrotransfer Of Different Control Plasmids Elicits Different Antitumor Effectiveness In B16.F10 Melanoma, Masa Bosnjak, Tanjo Jesenko, Urska Kamensek, Gregor Sersa, Jaka Lavrencak, Loree Heller, Maja Cemazar

Bioelectrics Publications

Several studies have shown that different control plasmids may cause antitumor action in different murine tumor models after gene electrotransfer (GET). Due to the differences in GET protocols, plasmid vectors, and experimental models, the observed antitumor effects were incomparable. Therefore, the current study was conducted comparing antitumor effectiveness of three different control plasmids using the same GET parameters. We followed cytotoxicity in vitro and the antitumor effect in vivo after GET of control plasmids pControl, pENTR/U6 scr and pVAX1 in B16.F10 murine melanoma cells and tumors. Types of cell death and upregulation of selected cytosolic DNA sensors and cytokines were …

Vital Signs, Winter 2018, Boonshoft School Of Medicine

Vital Signs

A thirty-six page newsletter created by the Boonshoft School of Medicine to document the current affairs of the school. This issue includes a variety of feature articles, alumni profiles, class notes, and more.

Intra-Arterial Nitroglycerin As Directed Acute Treatment In Experimental Ischemic Stroke, Michael E. Maniskas, Jill M. Roberts, Rebecca Trueman, Annastazia E. Learoyd, Amanda A. Gorman, Justin F. Fraser, Gregory J. Bix

Neuroscience Faculty Publications

BACKGROUND: Nitroglycerin (also known as glyceryl trinitrate (GTN)), a vasodilator best known for treatment of ischemic heart disease, has also been investigated for its potential therapeutic benefit in ischemic stroke. The completed Efficacy of Nitric Oxide in Stroke trial suggested that GTN has therapeutic benefit with acute (within 6 hours) transdermal systemic sustained release therapy.

OBJECTIVE: To examine an alternative use of GTN as an acute therapy for ischemic stroke following successful recanalization.

METHODS: We administered GTN IA following transient middle cerebral artery occlusion in mice. Because no standard dose of GTN is available following emergent large vessel occlusion, we …

Serum Tumor Necrosis Factor-Alpha Associates With Myocardial Oxygen Demand And Exercise Tolerance In Postmenopausal Women, Stephen J. Carter, David R. Bryan, William H. Neumeier, Stephen P. Glasser, Gary R. Hunter

Internal Medicine Faculty Publications

The functional implications of serum tumor necrosis factor-alpha (TNF-α), a marker of oxidative stress, on hemodynamic parameters at rest and during physical exertion are unclear. The aims of this investigation were to examine the independent associations of TNF-α on myocardial oxygen demand at rest and during submaximal exercise, while also evaluating the association of TNF-α on exercise tolerance. Forty, postmenopausal women, provided blood samples and completed a modified-Balke protocol to measure maximal oxygen uptake (VO_2max). Large artery compliance was measured by pulse contour analyses while rate-pressure product (RPP), an index of myocardial oxygen demand, was measured at rest …

Comparison Of Artificial Saliva Vs Saline Solution On Rate Of Suture Degradation In Oropharyngeal Surgery, Jenna W. Briddell, Luke Riexinger, Jove Graham, Donna M. Ebenstein

Faculty Journal Articles

IMPORTANCE Absorbable sutures are designed to degrade and lose strength over time. Manufacturers warn that exposure to various body fluids can change the estimated degradation rate of these sutures, but few studies have been conducted to quantify the degree of change associated with saliva.

OBJECTIVE To quantify the association of increased loss of strength of sutures over time after exposure to artificial saliva (hereinafter referred to as “saliva”).

DESIGN, SETTING, AND PARTICIPANTS This experimental in vitro study was conducted at Bucknell University (Lewisburg, Pennsylvania) from June 19, 2015, to July 4, 2015. No participants were involved. The loss of strength …

Intermittent Hypoxemia In Preterm Infants, Elie G. Abu Jawdeh

Theses and Dissertations--Clinical and Translational Science

Intermittent hypoxemia (IH) is defined as episodic drops in oxygen saturation (SpO₂). Virtually all preterm infants have IH events. Extremely preterm infants have hundreds of IH events per day. The extent of IH is not apparent clinically as accurately documenting cardiorespiratory events for day-to-day patient care management is challenging. High resolution pulse oximeters with 2 second averaging time are currently the ideal methods to measure IH. We have developed novel methods and processes to accurately and efficiently calculate an IH profile that reflects to spectrum of the problem.

The natural progression of IH is dynamic. There is low …

Role Of Sex Chromosomes In Sexual Dimorphism Of Angii-Induced Abdominal Aortic Aneurysms, Yasir Alsiraj

Theses and Dissertations--Pharmacology and Nutritional Sciences

Abdominal aortic aneurysms (AAAs), a permanent dilation in the abdominal region of the aorta, is a highly sexually dimorphic disease. AAAs prevalence is ranging from 4-10 fold higher in males than females. Defining the mechanistic basis for reduced (in females) or increased (in males) AAA formation and progression may uncover potential therapeutic targets. The majority of studies examining sexual dimorphism focus on the role of sex hormones. However, genes residing on sex chromosomes, in addition to sex hormones, may contribute to sexual dimorphism of AAAs. For example, the X chromosome contains about 5% of the whole genome, but the role …

Effect Of Hemiepiphysiodesis On The Growth Plate: The Histopathological Changes And Mechanism Exploration Of Recurrence In Mini Pig Model., Jing Ding, Jin He, Zhi-Qiang Zhang, Zhen-Kai Wu, Fang-Chun Jin

Manuscripts, Articles, Book Chapters and Other Papers

Purpose: Hemiepiphysiodesis has been widely used to correct angular deformity of long bone in immature patients. However, there is a limited knowledge about the biomechanical effect of this technique on the histopathological changes of the growth plate and the mechanism of recurrence of malformation after implant removal. We aimed to evaluate the biomechanical effect of hemiepiphysiodesis on the histopathological changes of the growth plate and the mechanism of recurrence of malformation after implant removal in Bama miniature pigs, and to explore the role of asymmetric stress during this procedure.

Methods: Eight 3-month-old male Bama miniature pigs sustained surgeries on the …

Microtubule Imaging Reveals Cytoskeletal Deficit Predisposing The Retinal Ganglion Cell Axons To Atrophy In Dba/2j, Denis Sharoukhov, Festa Bucinca-Cupallari, Hyungsik Lim

Publications and Research

PURPOSE: Glaucoma is characterized by progressive loss of the retinal ganglion cells (RGCs) and their axons. Here we test an outstanding notion that microtubules (MTs) within RGC axons degrade before the loss of morphology (‘‘MT hypothesis’’).

METHODS: The integrity of axonal MTs was interrogated by intrinsic second-harmonic generation (SHG) microscopy. Using DBA/2J mice as a model of glaucoma and DBA/2J-Gpnmbþ as a nonglaucomatous control, the relationship between MT disruption and morphology was quantitatively examined as a function of age and sex in the fresh retinal wholemounts.

RESULTS: The mean SHG density (i.e., the mean SHG intensity per thickness) was significantly …

Down Syndrome, Beta-Amyloid And Neuroimaging, Elizabeth Head, Alex M. Helman, David K. Powell, Frederick A. Schmitt

Sanders-Brown Center on Aging Faculty Publications

This review focuses on the role of Aβ in AD pathogenesis in Down syndrome and current approaches for imaging Aβ in vivo. We will describe how Aβ deposits with age, the posttranslational modifications that can occur, and detection in biofluids. Three unique case studies describing partial trisomy 21 cases without APP triplication, and the occurrences of low level mosaic trisomy 21 in an early onset AD patient are presented. Brain imaging for Aβ includes those by positron emission tomography and ligands (Pittsburgh Compound B, Florbetapir, and FDDNP) that bind Aβ have been published and are summarized here. In combination, we …

Brain-Derived Neurotrophic Factor As A Biomarker For Aging And Dementia, Krishna Lajwanti Bharani

MUSC Theses and Dissertations

The number of people with dementia due to Alzheimer’s disease (AD) is increasing worldwide. Although AD pathology begins well before clinical symptoms are apparent, identifying individuals at risk of developing AD to provide early interventions is still a challenge. Brain-derived neurotrophic factor (BDNF) is produced by neurons and glial cells and has complex interactions with AD pathology. BDNF also crosses the blood-brain barrier and can be measured in serum or plasma. In this dissertation, I investigated the biomarker potential of serum BDNF for AD using post mortem human samples, an aged rat model of cognitive impairment, and blood samples from …

Mechanisms And Potential Therapy On Disrupted Blood Pressure Circadian Rhythm In Diabetes, Tianfei Hou

Theses and Dissertations--Pharmacology and Nutritional Sciences

Arterial blood pressure (BP) undergoes a 24-hour oscillation that peaks in the active day and reaches a nadir at night during sleep in humans. Reduced nocturnal BP fall (also known as non-dipper) is the most common disruption of BP circadian rhythm and is associated with increased risk of untoward cardiovascular events and target organ injury. Up to 75% of diabetic patients are non-dippers. However, the mechanisms underlying diabetes associated non-dipping BP are largely unknown. To address this important question, we generated a novel diabetic db/db-mPer2^Luc mouse model (db/db-mPer2^Luc) that allows quantitatively measuring of mPER2 protein oscillation …

Antibody Dependent Enhancement Of Visceral Leishmaniasis, Alan K. Mcnolty

All Master's Theses

Leishmaniasis is a parasitic disease caused by protozoans of the genus Leishmania. This vector-born disease, transmitted by biting phlebotomine sandflies, typically manifests in one of three ways. The cutaneous form of the disease is characterized by localized lesions of the skin and is by far the most common manifestation. The visceral form of the disease is caused by parasitic infiltration of internal organs, particularly the spleen, liver, and bone marrow. The mucocutaneous form is caused by parasitic infection of the mucosa in the nose or mouth. While cutaneous leishmaniasis (CL) is often self-healing, visceral leishmaniasis (VL) is fatal if …

Neonatal Safety Information Reported To The Fda During Drug Development Studies., Debbie Avant, Gerri Baer, Jason N. Moore, Panli Zheng, Alfred Sorbello, Ron Ariagno, Lynne Yao, Gilbert J. Burckart, Jian Wang

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Relatively few neonatal drug development studies have been conducted, but an increase is expected with the enactment of the Food and Drug Administration Safety and Innovation Act (FDASIA). Understanding the safety of drugs studied in neonates is complicated by the unique nature of the population and the level of illness. The objective of this study was to examine neonatal safety data submitted to the FDA in studies pursuant to the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA) between 1998 and 2015.

METHODS: FDA databases were searched for BPCA and/or PREA studies that enrolled …

A Novel Biosimulation Task Trainer For The Deliberate Practice Of Resuscitative Hysterotomy., Lawrence Lau, Dimitrios Papanagnou, Elaine Smith, Crystal Waters, Elizabeth Teixeira, Xiao Chi Zhang

Department of Emergency Medicine Faculty Papers

Resuscitative hysterotomy is a daunting and rarely performed procedure in the emergency department (ED). Given the paucity of clinical exposure to this intervention, resuscitative hysterotomy is an ideal opportunity for simulation-mediated deliberate practice. The authors propose a novel training program using a homegrown, realistic, simulation device as a means to practice resuscitative hysterotomy. Two high-fidelity, tissue-based task-trainer models were constructed and tested on a convenience sample of 14 emergency medicine (EM) residents. The simulated human placenta, bladder, amniotic sac, and uterus were constructed through the use of porcine skin, porcine stomach, transparent plastic bag, Foley tubing, and squid mantle, all …

The Path Report Volume 2 Issue 3, Pathology Department, New York Medical College

The Path Report

No abstract provided.

High Heterotrophic Counts In Potable Water And Antimicrobial Resistance Among Indicator Organisms In Two Peri-Urban Communities Of Karachi, Pakistan, Sadia Shakoor, Imran Ahmed, Saima Mukhtiar, Israr Ahmed, Farzeen Hirani, Shazia Sultana, Rumina Hasan

Department of Pathology and Laboratory Medicine

Objective: Fecal contamination of potable water leads to unsafe water supply. Although many urban areas of large metropolitan cities receive safe water, peri-urban areas are often not monitored by public health authorities and water supply and quality remain unknown. We assessed microbiological quality and rates of antimicrobial resistance in viable indicator bacteria in two peri-urban communities of Karachi, Pakistan. Water samples were collected over 5 months (October 2015 to February 2016) from these peri-urban communities and samples were processed for microbiological quality as per Standing Committee of Analysts, United Kingdom and World Health Organization guidelines and criteria for drinking water. …