Medical Specialties Commons^™

Left Ventricular Mechanical Dysfunction In Diet-Induced Obese Mice Is Exacerbated During Inotropic Stress: A Cine Dense Cardiovascular Magnetic Resonance Study, Christopher M. Haggerty, Andrea C. Mattingly, Sage P. Kramer, Cassi M. Binkley, Linyuan Jing, Jonathan D. Suever, David K. Powell, Richard J. Charnigo, Frederick H. Epstein, Brandon K. Fornwalt

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Obesity is a risk factor for cardiovascular disease. There is evidence of impaired left ventricular (LV) function associated with obesity, which may relate to cardiovascular mortality, but some studies have reported no dysfunction. Ventricular function data are generally acquired under resting conditions, which could mask subtle differences and potentially contribute to these contradictory findings. Furthermore, abnormal ventricular mechanics (strains, strain rates, and torsion) may manifest prior to global changes in cardiac function (i.e., ejection fraction) and may therefore represent more sensitive markers of cardiovascular disease. This study evaluated LV mechanics under both resting and stress conditions with the hypothesis …

Identifying The Critical Domain Of Ll-37 Involved In Mediating Neutrophil Activation In The Presence Of Influenza Virus: Functional And Structural Analysis., Shweta Tripathi, Guangshun Wang, Mitchell White, Michael Rynkiewicz, Barbara Seaton, Kevan Hartshorn

Journal Articles: Pathology and Microbiology

The human cathelicidin LL-37 has been shown to play a role in host defense against influenza A viruses (IAV) through direct antiviral effects and through modulating inflammatory responses to infection. We recently showed that LL-37 increases neutrophil respiratory burst and neutrophil extracellular trap (NET) responses to IAV through engaging formyl peptide receptor 2 (FPR-2). In this paper we show that a fragment of LL-37, GI-20, which is composed of the central helical segment of the peptide, has similar effects as LL-37 on neutrophil activation. In addition to increasing respiratory burst and NET responses of the cells to IAV through an …

Staphylococcus Aureus Biofilms Induce Macrophage Dysfunction Through Leukocidin Ab And Alpha-Toxin., Tyler D. Scherr, Mark L. Hanke, Ouwen Huang, David B.A. James, Alexander R. Horswill, Kenneth W. Bayles, Paul D. Fey, Victor J. Torres, Tammy Kielian

Journal Articles: Pathology and Microbiology

UNLABELLED: The macrophage response to planktonic Staphylococcus aureus involves the induction of proinflammatory microbicidal activity. However, S. aureus biofilms can interfere with these responses in part by polarizing macrophages toward an anti-inflammatory profibrotic phenotype. Here we demonstrate that conditioned medium from mature S. aureus biofilms inhibited macrophage phagocytosis and induced cytotoxicity, suggesting the involvement of a secreted factor(s). Iterative testing found the active factor(s) to be proteinaceous and partially agr-dependent. Quantitative mass spectrometry identified alpha-toxin (Hla) and leukocidin AB (LukAB) as critical molecules secreted by S. aureus biofilms that inhibit murine macrophage phagocytosis and promote cytotoxicity. A role for Hla …

Subclavian Vein Stenosis/Occlusion Following Transvenous Cardiac Pacemaker And Defibrillator Implantation: Incidence, Pathophysiology And Current Management, Brian O'Leary, Suhail Allaqaband

Journal of Patient-Centered Research and Reviews

Subclavian vein stenosis is a common, but usually asymptomatic, complication following cardiac device placement. In addition to reviewing the literature on incidence, pathogenesis and management options for this important clinical problem, we describe two cases of symptomatic subclavian vein occlusion following pacemaker/defibrillator placement and successful treatment with venoplasty and stenting.

Vascular Medicine: A ‘Primary’ Specialty, Mark W. Mewissen

Journal of Patient-Centered Research and Reviews

N/A

Two Novel Genetic Variants In The Mineralocorticoid Receptor Gene Associated With Spontaneous Preterm Birth, Inge Christiaens, Q. Wei Ang, Lindsay N. Gordon, Xin Fang, Scott Williams

Dartmouth Scholarship

Background: Preterm birth is the leading cause of mortality and morbidity in newborn infants. Its etiology is multifactorial with genes and environmental factors, including chronic maternal stress, contributing to its risk. Our objective was to investigate whether single nucleotide polymorphisms (SNPs) in genes involved in the stress response are associated with spontaneous preterm birth using a candidate gene approach.

Methods: A total of 210 cases (singleton spontaneous preterm birth at <37 >weeks) and 412 controls (singleton term birth at 38–42 weeks without a history of preterm birth) were studied. High quality maternal DNA was available from saliva samples of 190 cases …

Mechanisms Of Immunological Tolerance In Central Nervous System Inflammatory Demyelination., Elisabeth R. Mari, Jason N. Moore, Guang-Xian Zhang, A. M. Rostami

Department of Neurology Faculty Papers

Multiple sclerosis is a complex autoimmune disease of the central nervous system that results in a disruption of the balance between pro-inflammatory and anti-inflammatory signals in the immune system. Given that central nervous system inflammation can be suppressed by various immunological tolerance mechanisms, immune tolerance has become a focus of research in the attempt to induce long-lasting immune suppression of pathogenic T cells. Mechanisms underlying this tolerance induction include induction of regulatory T cell populations, anergy and the induction of tolerogenic antigen-presenting cells. The intravenous administration of encephalitogenic peptides has been shown to suppress experimental autoimmune encephalomyelitis and induce tolerance …

Myricetin Inhibits Proliferation Of Cisplatin-Resistant Cancer Cells Through A P53-Dependent Apoptotic Pathway, Haizhi Huang, Allen Y. Chen, Xingqian Ye, Bingyun Li, Yon Rojanasakul, Gary O. Rankin, Yi Charlie Chen

Pharmaceutical Science and Research

Cisplatin is a commonly used drug for cancer treatment by crosslinking DNA, leading to apoptosis of cancer cells, resistance to cisplatin treatment often occurs, leading to relapse. Therefore, there is a need for the development of more effective treatment strategies that can overcome chemoresistance. Myricetin is a flavonoid from fruits and vegetables, showing anticancer activity in various cancer cells. In this study, we found myricetin exhibited greater cytotoxicity than cisplatin in two cisplatin-resistant ovarian cancer cell lines, OVCAR-3 and A2780/CP70, and it was less cytotoxic to the normal ovarian cell line IOSE-364. Myricetin selectively induced apoptosis in both cisplatin-resistant cancer …

Reversal Of Aging-Related Neuronal Ca2+ Dysregulation And Cognitive Impairment By Delivery Of A Transgene Encoding Fk506-Binding Protein 12.6/1b To The Hippocampus, John C. Gant, Kuey-Chu Chen, Inga Kadish, Eric M. Blalock, Olivier Thibault, Nada M. Porter, Philip W. Landfield

Pharmacology and Nutritional Sciences Faculty Publications

Brain Ca(2+) regulatory processes are altered during aging, disrupting neuronal, and cognitive functions. In hippocampal pyramidal neurons, the Ca(2+)-dependent slow afterhyperpolarization (sAHP) exhibits an increase with aging, which correlates with memory impairment. The increased sAHP results from elevated L-type Ca(2+) channel activity and ryanodine receptor (RyR)-mediated Ca(2+) release, but underlying molecular mechanisms are poorly understood. Previously, we found that expression of the gene encoding FK506-binding protein 12.6/1b (FKBP1b), a small immunophilin that stabilizes RyR-mediated Ca(2+) release in cardiomyocytes, declines in hippocampus of aged rats and Alzheimer's disease subjects. Additionally, knockdown/disruption of hippocampal FKBP1b in young rats augments neuronal Ca(2+) responses. …

Gallic Acid, A Phenolic Compound, Exerts Anti-Angiogenic Effects Via The Pten/Akt/Hif-1Α/Vegf Signaling Pathway In Ovarian Cancer Cells, Zhiping He, Allen Y. Chen, Yon Rojanasakul, Gary O. Rankin, Yi Charlie Chen

Pharmaceutical Science and Research

Gallic acid (GA), a polyphenol, is widely found in numerous fruits and vegetables, particularly in hickory nuts. In the present study, we found that gallic acid, a natural phenolic compound isolated from fruits and vegetables, had a more potent growth inhibitory effect on two ovarian cancer cell lines, OVCAR-3 and A2780/CP70, than the effect on a normal ovarian cell line, IOSE-364. These results demonstrated that GA selectively inhibits the growth of cancer cells. Gene expression was examined by ELISA and western blot analysis, and gene pathways were examined by luciferase assay. It was found that GA inhibited VEGF secretion and …

Toll-Like Receptors And Dectin-1, A C-Type Lectin Receptor, Trigger Divergent Functions In Cns Macrophages, John C. Gensel, Yan Wang, Zhen Guan, Kyle A. Beckwith, Kaitlyn J. Braun, Ping Wei, Dana M. Mctigue, Phillip G. Popovich

Spinal Cord and Brain Injury Research Center Faculty Publications

Spinal cord injury (SCI) activates macrophages, endowing them with both reparative and pathological functions. The mechanisms responsible for these divergent functions are unknown but are likely controlled through stochastic activation of different macrophage receptor subtypes. Various danger-associated molecular patterns released from dying cells in the injured spinal cord likely activate distinct subtypes of macrophage pattern recognition receptors, including bacterial toll-like receptors (TLRs) and fungal C-type lectin receptors (e.g., dectin-1). To determine the in vivo consequences of activating these receptors, ligands specific for TLR2 or dectin-1 were microinjected, alone or in combination, into intact spinal cord. Both ligands elicit a florid …

A Self-Lysis Pathway That Enhances The Virulence Of A Pathogenic Bacterium, Kirsty A. Mcfarland, Emily L. Dolben, Michele Leroux, Tracy K. Kambara, Kathryn Ramsey, Robin Kirkpatrick, Joseph Mougous, Deborah Hogan, Simon Dove

Dartmouth Scholarship

In mammalian cells, programmed cell death (PCD) plays important roles in development, in the removal of damaged cells, and in fighting bacterial infections. Although widespread among multicellular organisms, there are relatively few documented instances of PCD in bacteria. Here we describe a potential PCD pathway in Pseudomonas aeruginosa that enhances the ability of the bacterium to cause disease in a lung infection model. Activation of the system can occur in a subset of cells in response to DNA damage through cleavage of an essential transcription regulator we call AlpR. Cleavage of AlpR triggers a cell lysis program through de-repression of …

Bacterially-Based Immune Challenges And Trauma Elicit Terminal Investment In Male Aedes Aegypti, Molly K. Schumacher

Theses and Dissertations

Investment in life history traits such as immune function and reproduction is constrained by finite available resources. A cost-of-immunity trade-off may occur in response to infection when resources are diverted away from reproductive effort and into an immune response. Alternatively, an infected individual may enhance reproductive effort to maximize terminal reproductive success in response to the survival threat inherent to infection (terminal investment). We measured male Aedes aegypti reproductive behavior following inoculations with: living bacteria; killed bacteria as an immune elicitor; and a sham control. Mating competitiveness relative to naïve males was also determined through a binary mate choice experiment …

Turning Up The Heat On Malignant Hyperthermia, Katie Carroll

Nursing Student Class Projects (Formerly MSN)

Surgeries are common, everyday procedures within the walls of America’s hospitals. According to Orser, Mazer, and Baker (2008), more than forty million patients in North America are given anesthetics annually. One of the major complications of anesthesia is malignant hyperthermia: a hyper-metabolic state that affects skeletal muscles. If left uncontrolled, malignant hyperthermia can cause multiple reactions within the body leading to metabolic and respiratory acidosis, cardiac dysrhythmias, kidney failure, coagulopathy, neurologic injury, and ultimately death (Seifert, Wahr, Pace, Cochrane, & Bagnola 2014). The incidence of this condition is estimated to be 1:15,000 in children and 1:20,000-50,000 in adults (Redmond, 2001). …

Differences In Health-Related Behaviors And Attitudes Between Urban, Rural, And Isolated Households In Western West Virginia, Michael Newsome Phd, Tim Hazelett, Monika Sawhney Phd, Msw

Economics Faculty Research

This study uses data from a 2013 survey of 275 randomly sampled households across nine counties in western West Virginia to examine the significant differences between the health behaviors and attitudes of rural and isolated populations. The results show that age, education, and income are significant factors in explaining differences in health-related behaviors and attitudes for all urban, rural and isolated respondents. However, after controlling for socio-demographic differences, isolation is found to have only a few significant effects, and some of the effects run counter to stereotypes of isolated populations. Rural respondents are significantly more likely than isolated respondents to …

Effect Of Sirna Pre-Exposure On Subsequent Response To Sirna Therapy, Hamidreza Montazeri Aliabadi, Parvin Mahdipoor, Cezary Kucharski, Nicole Chan, Hasan Uludag

Pharmacy Faculty Articles and Research

PURPOSE. An alternative cancer therapy based on RNA interference (RNAi) has shown considerable promise but the possibility of resistance development is not known. This study explored the possibility of therapeutic resistance against siRNA nanoparticles in human cancer cells. METHODS. Two approaches to siRNA treatment were undertaken using lipid-modified polyethylenimines, a single high concentration (shock) and repeated increasing concentrations (gradual). The targets were Mcl-1, RPS6KA5 and KSP in MDA-MB-435 cells. RESULTS. There was no evidence of resistance development in shock-treated cells, while the decrease in mRNA levels of targeted proteins was not as robust in naïve cells in gradual treatment. However, …

Taranis Functions With Cyclin A And Cdk1 In A Novel Arousal Center To Control Sleep In Drosophila., Dinis J.S. Afonso, Die Liu, Daniel R. Machado, Huihui Pan, James E.C. Jepson, Dragana Rogulja, Kyunghee Koh

Department of Neuroscience Faculty Papers

Sleep is an essential and conserved behavior whose regulation at the molecular and anatomical level remains to be elucidated. Here, we identify TARANIS (TARA), a Drosophila homolog of the Trip-Br (SERTAD) family of transcriptional coregulators, as a molecule that is required for normal sleep patterns. Through a forward-genetic screen, we isolated tara as a novel sleep gene associated with a marked reduction in sleep amount. Targeted knockdown of tara suggests that it functions in cholinergic neurons to promote sleep. tara encodes a conserved cell-cycle protein that contains a Cyclin A (CycA)-binding homology domain. TARA regulates CycA protein levels and genetically …

Exogenous 17-Β Estradiol Administration Blunts Progression Of Established Angiotensin Ii-Induced Abdominal Aortic Aneurysms In Female Ovariectomized Mice, Sean E. Thatcher, Xuan Zhang, Shannon Woody, Yu Wang, Yasir Alsiraj, Richard Charnigo, Alan Daugherty, Lisa A. Cassis

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Abdominal aortic aneurysms (AAAs) occur predominately in males. However, AAAs in females have rapid growth rates and rupture at smaller sizes. Mechanisms contributing to AAA progression in females are undefined. We defined effects of ovariectomy, with and without 17-β estradiol (E2), on progression of established angiotensin II (AngII)-induced AAAs in female mice.

METHODS: We used neonatal testosterone exposures at 1 day of age to promote susceptibility to AngII-induced AAAs in adult female Ldlr^-/- mice. Females were infused with AngII for 28 days to induce AAAs, and then stratified into groups that were sham, ovariectomized (Ovx, vehicle), or Ovx …

Irreversible Dual Inhibitory Mode: The Novel Btk Inhibitor Pls-123 Demonstrates Promising Anti-Tumor Activity In Human B-Cell Lymphoma., Ning Ding, Xitao Li, Yunfei Shi, Lingyan Ping, Lina Wu, Kai Fu, Lixia Feng, Xiaohui Zheng, Yuqin Song, Zhengying Pan, Jun Zhu

Journal Articles: Pathology and Microbiology

The B-cell receptor (BCR) signaling pathway has gained significant attention as a therapeutic target in B-cell malignancies. Recently, several drugs that target the BCR signaling pathway, especially the Btk inhibitor ibrutinib, have demonstrated notable therapeutic effects in relapsed/refractory patients, which indicates that pharmacological inhibition of BCR pathway holds promise in B-cell lymphoma treatment. Here we present a novel covalent irreversible Btk inhibitor PLS-123 with more potent anti-proliferative activity compared with ibrutinib in multiple cellular and in vivo models through effective apoptosis induction and dual-action inhibitory mode of Btk activation. The phosphorylation of BCR downstream activating AKT/mTOR and MAPK signal pathways …

Telemetric Blood Pressure Assessment In Angiotensin Ii-Infused Apoe-/- Mice: 28 Day Natural History And Comparison To Tail-Cuff Measurements, Christopher M. Haggerty, Andrea C. Mattingly, Ming C. Gong, Wen Su, Alan Daugherty, Brandon K. Fornwalt

Saha Cardiovascular Research Center Faculty Publications

Abdominal aortic aneurysm (AAA) is a disease of the aortic wall, which can progress to catastrophic rupture. Assessment of mechanical characteristics of AAA, such as aortic distensibility, may provide important insights to help identify at-risk patients and understand disease progression. While the majority of studies on this topic have focused on retrospective patient data, recent studies have used mouse models of AAA to prospectively evaluate the evolution of aortic mechanics. Quantification of aortic distensibility requires accurate measurement of arterial blood pressure, particularly pulse pressure, which is challenging to perform accurately in murine models. We hypothesized that volume/pressure tail-cuff measurements of …

Links Between Anr And Quorum Sensing In Pseudomonas Aeruginosa Biofilms, John H. Hammond, Emily F. Dolben, T. Jarrod Smith, Sabin Bhuju, Deborah Hogan

Dartmouth Scholarship

In Pseudomonas aeruginosa, the transcription factor Anr controls the cellular response to low oxygen or anoxia. Anr activity is high in oxygen-limited environments, including biofilms and populations associated with chronic infections, and Anr is necessary for persistence in a model of pulmonary infection. In this study, we characterized the Anr regulon in biofilm-grown cells at 1% oxygen in the laboratory strain PAO1 and in a quorum sensing (QS)-deficient clinical isolate, J215. As expected, transcripts related to denitrification, arginine fermentation, high-affinity cytochrome oxidases, and CupA fimbriae were lower in the Δanr derivatives. In addition, we observed that transcripts associated with quorum …

Visual Feedback Dominates The Sense Of Agency For Brain-Machine Actions, Nathan Evans, Steven Gale, Aaron Schurger, Olaf Blanke

Psychology Faculty Articles and Research

Recent advances in neuroscience and engineering have led to the development of technologies that permit the control of external devices through real-time decoding of brain activity (brain-machine interfaces; BMI). Though the feeling of controlling bodily movements (sense of agency; SOA) has been well studied and a number of well-defined sensorimotor and cognitive mechanisms have been put forth, very little is known about the SOA for BMI-actions. Using an on-line BMI, and verifying that our subjects achieved a reasonable level of control, we sought to describe the SOA for BMI-mediated actions. Our results demonstrate that discrepancies between decoded neural activity and …

Desmin Common Mutation Is Associated With Multi-Systemic Disease Manifestations And Depletion Of Mitochondria And Mitochondrial Dna., Elizabeth M. Mccormick, Lawrence C. Kenyon, Marni J. Falk

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Desmin (DES) is a major muscle scaffolding protein that also functions to anchor mitochondria. Pathogenic DES mutations, however, have not previously been recognized as a cause of multi-systemic mitochondrial disease. Here, we describe a 45-year-old man who presented to The Children's Hospital of Philadelphia Mitochondrial-Genetics Diagnostic Clinic for evaluation of progressive cardiac, neuromuscular, gastrointestinal, and mood disorders. Muscle biopsy at age 45 was remarkable for cytoplasmic bodies, as well as ragged red fibers and SDH positive/COX negative fibers that were suggestive of a mitochondrial myopathy. Muscle also showed significant reductions in mitochondrial content (16% of control mean for citrate synthase …

Astrocyte Morphology, Heterogeneity, And Density In The Developing African Giant Rat (Cricetomys Gambianus), Matthew A. Olude, Oluwaseun A. Mustapha, Oluwatunde A. Aderounmu, James O. Olopade, Amadi O. Ihunwo

Brain and Mind Institute

Astrocyte morphologies and heterogeneity were described in male African giant rats (AGR; Cricetomys gambianus, Waterhouse) across three age groups (five neonates, five juveniles, and five adults) using Silver impregnation method and immunohistochemistry against glial fibrillary acidic protein. Immunopositive cell signaling, cell size and population were least in neonates, followed by adults and juveniles, respectively. In neonates, astrocyte processes were mostly detected within the glia limitans of the mid and hind brain; their cell bodies measuring 32 ± 4.8 μm in diameter against 91 ± 5.4 μm and 75 ± 1.9 μm in juveniles and adults, respectively. Astrocyte heterogeneity in …

Novel Advances In Alzheimer's Disease, Jacob P. Naumann

The Downtown Review: An Interdisciplinary Journal Written and Peer-Reviewed by Mandel Honors College Students at Cleveland State University

Alzheimer’s disease, the most common form of dementia in adults, is a progressive degenerative neurological disease that affects memory, cognition, and behavior. Dr. Alois Alzheimer discovered and diagnosed the irreversible disease in 1906 after documenting the famous case of Auguste Deter.¹ Since the discovery of the disease, numerous advances have made it possible to not only better understand the causal factors, but also to improve the medical diagnosis and preventative measures that healthcare providers can implement. For the first time since 1984, the National Institute on Aging (NIAA) and the Alzheimer’s Association (AA) proposed and published new diagnostic guideline …

Endoscopic Mucosal Resection And Radiofrequency Ablation For Intramucosal Adenocarcinoma In The Background Of Barrett’S Esophagus: A Case Series, Bonnie Patek Do, Patrick Hickey Do, Hiral N. Shah Md, Shashin Shah Md

Department of Medicine

No abstract provided.

Undifferentiated Carcinoma With Osteoclast-Like Giant Cells Of The Pancreatic Tail, Patrick Hickey Do, Ranjit R. Nair Md, Victoria A. Loven Md, Jeffrey Brodsky Md, Hiral N. Shah Md

Department of Medicine

No abstract provided.

Idiopathic Pulmonary Hemosiderosis: A Rare Cause Of Hemoptysis In Adults, Michael Kalil Do, B Miller Do, Ryan Rogers Do, Vanessa Ribaudo Kaufman Md

Department of Medicine

No abstract provided.

Cerium Oxide Nanoparticles Inhibit Lipopolysaccharide Inducedmap Kinase/Nf-Kb Mediated Severe Sepsis, Mani Maheshwari, Nandini Manne Phd, Shinichi Asano, Eric Blough, Kevin M. Rice, Niraj Nepa,, Erin Fankhanel

Pharmaceutical Science and Research

The life threatening disease of sepsis is associated with high mortality. Septic patient survivability with currently available treatments has failed to improve. The purpose of this study was to evaluate whether lipopolysaccharide (LPS) induced sepsis mortality and associated hepatic dysfunction can be prevented by cerium oxide nanoparticles (CeO2NPs) treatment in male Sprague Dawley rats. Here we provide the information about the methods processing of raw data related to our study published in Biomaterials (Selvaraj et al., Biomaterials, 2015, In press) and Data in Brief (Selvaraj et al., Data in Brief, 2015, In Press). The data present here provides confirmation …

Emergency Cardiac Care In Athletic Training Education, Erica M. Filep

Masters Theses, 2010-2019

In the field of athletic training, preventing sudden cardiac arrest (SCA) has become a vital component of undergraduate athletic training students’ education. Specifically, SCA is the “leading cause of death in young athletes due to a structural cardiac abnormality” (Casa et. al, 2012, p. 15). Numerous studies about sudden death in athletics have been conducted but there is a gap in educational literature. Teaching students how to respond to catastrophic injury or illness is still an area that needs to be expanded upon. Educational competencies and standards have rapidly evolved with each edition of the National Athletic Trainers’ Association (NATA) …