Digital Commons Network^™

Of Pools, Oceans, And The Dead Sea., Samir K. Ballas

Department of Medicine Faculty Papers

In a comprehensive study in this issue of Blood, Carden and colleagues describe the importance of the tonicity of IV fluids used in the treatment of patients with sickle cell disease (SCD) during vaso-occlusive crises (VOCs). Hypertonic fluids decreased sickle red blood cell (sRBC) deformability, increased occlusion, and increased sRBC adhesion in microfluidic human microvasculature models. Hypotonic fluids decreased sRBC adhesion but prolonged sRBC transit time. Fluids with intermediate tonicities resulted in optimal changes that reduced the risk of vaso-occlusion. © 2017 by The American Society of Hematology.

A Simple And Accurate Rule-Based Modeling Framework For Simulation Of Autocrine/Paracrine Stimulation Of Glioblastoma Cell Motility And Proliferation By L1cam In 2-D Culture., Justin Caccavale, David Fiumara, Michael Stapf, Liedeke Sweitzer, Hannah J. Anderson, Jonathan Gorky, Prasad Dhurjati, Deni S. Galileo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Glioblastoma multiforme (GBM) is a devastating brain cancer for which there is no known cure. Its malignancy is due to rapid cell division along with high motility and invasiveness of cells into the brain tissue. Simple 2-dimensional laboratory assays (e.g., a scratch assay) commonly are used to measure the effects of various experimental perturbations, such as treatment with chemical inhibitors. Several mathematical models have been developed to aid the understanding of the motile behavior and proliferation of GBM cells. However, many are mathematically complicated, look at multiple interdependent phenomena, and/or use modeling software not freely available to the research …

Editorial: Murine Models Of Leukemia And Lymphoma, Christine E. Cutucache, Pierluigi Porcu

Kimmel Cancer Center Faculty Papers

No abstract provided.

A Rare Case Of Hemophagocytic Lymphohistiocytosis Of Unknown Etiology, Ida Micaily, Marie Helene Gagnon, Richard Friedenheim, Jason A. Damsker

Division of Internal Medicine Faculty Papers & Presentations

Hemophagocytic lymphohistiocytosis (HLH) is an uncommon cytokine storm syndrome marked which can cause high mortality. In adults, acquired HLH usually has an underlying infectious, autoimmune or malignant process that triggers the syndrome. In this case report, we present a 64-year old Caucasian male presenting with productive cough, fevers, weight loss and altered mental status who was ultimately found to have HLH of unknown etiology.

Strategic Leadership Newsletter: Volume 3, Number 4, Larry M. Starr Phd

Leadership Doctorates Newsletter (Formerly Strategic Leadership Newsletter)

Jefferson Strategic Leadership Newsletter reports information relevant to the Jefferson (Philadelphia University + Thomas Jefferson University) Doctor of Management Program in Strategic Leadership (DSL) and its community including personal and professional events and accomplishments, new practices, research, opportunities, and suggestions. You are encouraged to forward the Newsletter to friends and colleagues to expand awareness and to brand yourself as a community member. You are also invited to recommend people or organizations to be added to the mailing list. Contact Jefferson Strategic Leadership Newsletter by emailing starrl@philau.edu.

Employing Pharmacy Students To Improve The Medication Use Process For Underserved Patients With A History Of Mental Health Or Substance Use Disorders, Ashley Maister, Pharmd Candidate, Toni Campanella, Pharmd Candidate, Roshni S. Patel, Pharmd, Bcps

College of Pharmacy Posters

Project HOME is a non-profit organization in Philadelphia that provides housing, employment opportunities, medical care, and education for chronically homeless individuals with serious mental health conditions.

One nurse oversees the medication use process at three of Project HOME’s residences; however, non-clinical staff are responsible for carrying out the medication use process.

The purpose of this project was to identify how the Jefferson College of Pharmacy’s APhA-ASP chapter could assist Project HOME with their medication-related needs and improve the medication use process.

A Novel Mutation In St14 At A Functionally Significant Amino Acid Residue Expands The Spectrum Of Ichthyosis-Hypotrichosis Syndrome., Leila Youssefian, Andrew Touati, Amir Hossein Saeidian, Omid Zargari, Sirous Zeinali, Hassan Vahidnezhad, Jouni Uitto

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Mutations in the ST14 gene, encoding the serine protease matriptase, have been associated with ichthyosis-hypotrichosis syndrome (IHS), a Mendelian disorder with skin and hair manifestations which include, in addition to ichthyosis and hypotrichosis, hypohidrosis and follicular atrophoderma. However, the understanding of the specific consequences of mutations in ST14 on the development of this syndrome is incomplete.

RESULTS: Using a targeted next-generation sequencing array of 38 ichthyosis-associated genes on a large cohort of 180 ichthyosis patients from a primarily consanguineous background, a previously unreported homozygous p.Asp482Asn mutation in ST14 was identified in a patient with IHS. This mutation affects an …

Optimal Management Of Post-Traumatic Radioulnar Synostosis, Arthur Lee Osterman, Melissa S. Arief

Department of Orthopaedic Surgery Faculty Papers

Post-traumatic radioulnar synostosis is a rare complication after forearm or elbow injury that can result in loss of motion and significant disability. Risk factors include aspects of the initial trauma and of the surgical treatment of that trauma. Surgical intervention for synostosis is the standard of care and is determined based on the location of the bony bridge. Surgical timing is recommended between 6 months and 2 years with recent advocacy for the 6- to 12-month period after radiographs demonstrate bony maturation but early enough to prevent further stiffness and contractures. For most types of synostosis, surgical resection with interposition …

Reorganization Of Thalamic Intrinsic Connectivity Following Anterior Temporal Lobectomy, Xiaosong He, Chaitanya Ganne, Michael R. Sperling, Ashwini Sharan, Joseph I. Tracy

Department of Neurosurgery Posters

The thalamus has played a crucial role in determining surgical outcome following anterior temporal lobectomy (ATL) in temporal lobe epilepsy (TLE) (He, et al., 2017). Before successfully quantifying the impact of the thalamus on ATL outcomes, this structure’s own intrinsic connectivity must be understood. Accordingly, we characterize thalamic intrinsic connectivity through resting-state fMRI (rsfMRI) longitudinally, exploring its change pre- to post-surgery.

Intermediate-Term Risk Of Stroke Following Cardiac Procedures In A Nationally Representative Data Set., Laura Stein, Alison Thaler, John W. Liang, Stanley Tuhrim, Amit S. Dhamoon, Mandip S. Dhamoon

Department of Neurology Faculty Papers

BACKGROUND: Studies on stroke risk following cardiac procedures addressed only perioperative and long-term risk following limited higher-risk procedures, were poorly generalizable, and often failed to stratify by stroke type. We calculated stroke risk in the intermediate risk period following cardiac procedures compared with common noncardiac surgeries and medical admissions.

METHODS AND RESULTS: The Nationwide Readmissions Database contains readmission data for 49% of US admissions in 2013. We compared age-adjusted stroke readmission rates up to 90 days postdischarge. We used Cox regression to calculate hazard ratios, up to 1 year, of stroke risk comparing transcatheter aortic valve replacement versus surgical aortic …

Utilization Of Care By Infants With Neonatal Abstinence Syndrome In Delaware, Michele K. Savin, Dnp, Aprn, Nnp-Bc

College of Nursing Posters

Introduction: There is little information regarding use of expected well care by infants diagnosed with neonatal abstinence syndrome (NAS) post initial discharge. We describe expected and unexpected utilization of care by infants with NAS in the first year of life.

Methods: A de-identified State of Delaware Medicaid data set was obtained. Included were all infants with an ICD-9 code for NAS from 01/01/2012-12/31/2014. All associated medical claims were extracted for one year after birth. Utilization rates of primary care, immunizations, urgent or emergency care, and re-hospitalization were quantified.

Results: 499 of 522 babies were able to be fully analyzed. The …

Designing A New Model For Clinical Education: An Innovative Approach., Kathryn Shaffer, Beth Ann Swan, Mary Bouchaud

College of Nursing Faculty Papers & Presentations

To keep pace with the ever-changing health care delivery system, it is important to transform the way future nurses are educated, both in classroom and in clinical settings, to care for people along the life and care continuum, not only in acute-care settings. The purpose of this article is to describe a new approach to educating baccalaureate nursing students using immersion practicums that expose students to population health, transitions of care, care coordination, and the multiple roles a nurse engages in along the continuum. The curriculum includes 5 immersions, each with a specific life and care continuum focus to develop …

Platelet-Rich Plasma Injection With Percutaneous Needling For Recalcitrant Lateral Epicondylitis: Comparison Of Tenotomy And Fenestration Techniques., Michael P. Gaspar, Michael A. Motto, Sarah Lewis, Sidney M. Jacoby, Randall W. Culp, A. Lee Osterman, Patrick M. Kane

Department of Orthopaedic Surgery Faculty Papers

Background: Recalcitrant lateral epicondylitis (LE) is a common debilitating condition, with numerous treatment options of varying success. An injection of platelet-rich plasma (PRP) has been shown to improve LE, although it is unclear whether the method of needling used in conjunction with a PRP injection is of clinical importance.

Purpose: To determine whether percutaneous needle tenotomy is superior to percutaneous needle fenestration when each is combined with a PRP injection for the treatment of recalcitrant LE.

Study Design: Cohort study; Level of evidence, 3.

Methods: A total of 93 patients with recalcitrant LE were treated with a PRP injection and …

Three-Dimensional Context Rather Than Nls Amino Acid Sequence Determines Importin Α Subtype Specificity For Rcc1., Rajeshwer S. Sankhala, Ravi K. Lokareddy, Salma Begum, Ruth A. Pumroy, Richard E. Gillilan, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

Active nuclear import of Ran exchange factor RCC1 is mediated by importin α3. This pathway is essential to generate a gradient of RanGTP on chromatin that directs nucleocytoplasmic transport, mitotic spindle assembly and nuclear envelope formation. Here we identify the mechanisms of importin α3 selectivity for RCC1. We find this isoform binds RCC1 with one order of magnitude higher affinity than the generic importin α1, although the two isoforms share an identical NLS-binding groove. Importin α3 uses its greater conformational flexibility to wedge the RCC1 β-propeller flanking the NLS against its lateral surface, preventing steric clashes with its Armadillo-core. Removing …

The Technique Of S2-Alar-Iliac Screw Fixation: A Literature Review, Ai-Min Wu, Dong Chen, Chun-Hui Chen, Yu-Zhe Li, Li Tan Li Tang, Kevin Phan, Kern Singh, Brittany E. Haws, Daniele Vanni, Yusef I. Mosley, Srinivas K. Prasad, James Harrop, Zhong-Ke Lin, Yan Lin, Wen-Fei Ni, Xiang-Yang Wang

Department of Neurosurgery Faculty Papers

The distal fixation in thoracolumbar deformity surgery can be challenging for spine surgeons. When isolated S1-pedicle screws are utilized as the sole distal fixation in long thoracolumbar posterior constructs, there is a high rate of failure, due to loosening, breakage, and pseudarthrosis. Unfortunately, with iliac screw fixation the entry point at the posterior superior iliac spine requires considerable soft tissue dissection and may potentially increase the likelihood of wound complications. S2-alar-iliac (S2AI) screw fixation technique was developed recently to provide increased fixation with a lower profile screw and rod construct. These screws can be inserted with percutaneous or free hand …

Hmgcs2 Is A Key Ketogenic Enzyme Potentially Involved In Type 1 Diabetes With High Cardiovascular Risk., Sanket Kumar Shukla, Weijing Liu, Kunal Sikder, Sankar Addya, Amrita Sarkar, Yidong Wei, Khadija Rafiq

Center for Translational Medicine Faculty Papers

Diabetes increases the risk of Cardio-vascular disease (CVD). CVD is more prevalent in type 2 diabetes (T2D) than type 1 diabetes (T1D), but the mortality risk is higher in T1D than in T2D. The pathophysiology of CVD in T1D is poorly defined. To learn more about biological pathways that are potentially involved in T1D with cardiac dysfunction, we sought to identify differentially expressed genes in the T1D heart. Our study used T1D mice with severe hyperglycemia along with significant deficits in echocardiographic measurements. Microarray analysis of heart tissue RNA revealed that the T1D mice differentially expressed 10 genes compared to …

The Structure And C=C Vibrational Frequencies Of The All- Trans Polyenes C2nh2n+2(N=2-15), C2nh2n(Me)2(N=2-13), And C2nh2n(Tert-Butyl)2(N=2-5): Computational Results, George R. De Maré, Niny Z. Rao, Charles W. Block

Department of Biochemistry and Molecular Biology Faculty Papers

Carbon-carbon bond lengths and C=C vibrational frequencies are reported for the linear, all-trans unsubstituted C2nH2n+2 (n=2-15), methyl capped C2nH2nMe2 (n=2-13), and tert-butyl capped C2nH2n(tert-butyl)2 (n=2-5) polyenes (C2h) calculated at the B3LYP/6-311++G(d,p) level. The C=C/C-C bond length alternation remains evident at this level for the unsubstituted and methyl capped polyenes as the chain length increases; the center-most difference in the length of the C-C/C=C bonds is ~0.06 Å for C30H32 and C26H26Me2. The Ag, in-phase, harmonic C=C Raman frequency for the unsubstituted polyenes decreases from 1699.2 cm-1 (n = 2) to 1528.9 cm-1 (n=15); the anharmonic frequency decreases from 1651.5 cm-1 …

Synergy Of Two Low-Affinity Nlss Determines The High Avidity Of Influenza A Virus Nucleoprotein Np For Human Importin Α Isoforms., Wei Wu, Rajeshwer S. Sankhala, Tyler J Florio, Lixin Zhou, Nhan L.T. Nguyen, Ravi K. Lokareddy, Gino Cingolani, Nelly Panté

Department of Biochemistry and Molecular Biology Faculty Papers

The influenza A virus nucleoprotein (NP) is an essential multifunctional protein that encapsidates the viral genome and functions as an adapter between the virus and the host cell machinery. NPs from all strains of influenza A viruses contain two nuclear localization signals (NLSs): a well-studied monopartite NLS1 and a less-characterized NLS2, thought to be bipartite. Through site-directed mutagenesis and functional analysis, we found that NLS2 is also monopartite and is indispensable for viral infection. Atomic structures of importin α bound to two variants of NLS2 revealed NLS2 primarily binds the major-NLS binding site of importin α, unlike NLS1 that associates …

Antibiotic Spacers In Shoulder Arthroplasty: Comparison Of Stemmed And Stemless Implants., Eric M. Padegimas, Alexia Narzikul, Cassandra Lawrence, Benjamin A. Hendy, Joseph A. Abboud, Matthew L. Ramsey, Gerald R R. Williams, Surena Namdari

Department of Orthopaedic Surgery Faculty Papers

Background: Antibiotic spacers in shoulder periprosthetic joint infection deliver antibiotics locally and provide temporary stability. The purpose of this study was to evaluate differences between stemmed and stemless spacers.

Methods: All spacers placed from 2011 to 2013 were identified. Stemless spacers were made by creating a spherical ball of cement placed in the joint space. Stemmed spacers had some portion in the humeral canal. Operative time, complications, reimplantation, reinfection, and range of motion were analyzed.

Results: There were 37 spacers placed: 22 were stemless and 15 were stemmed. The stemless spacer population was older (70.9 ± 7.8 years vs. 62.8 …

Surgical Approaches To Adenocarcinoma Of The Gastroesophageal Junction: The Siewert Ii Conundrum., Andrew M. Brown, Danica N. Giugliano, Adam C. Berger, Michael J. Pucci, Francesco Palazzo

Department of Surgery Faculty Papers

BACKGROUND: The Siewert classification system for gastroesophageal junction adenocarcinoma has provided morphological and topographical information to help guide surgical decision-making. Evidence has shown that Siewert I and III tumors are distinct entities with differing epidemiologic and histologic characteristics and distinct patterns of disease progression, requiring different treatment. Siewert II tumors share some of the characteristics of type I and III lesions, and the surgical approach is not universally agreed upon. Appropriate surgical options include transthoracic esophagogastrectomy, transhiatal esophagectomy, and transabdominal extended total gastrectomy.

PURPOSE: A review of the available evidence of the surgical management of Siewert II tumors is presented. …

Plekhg5-Regulated Autophagy Of Synaptic Vesicles Reveals A Pathogenic Mechanism In Motoneuron Disease., Patrick Lüningschrör, Beyenech Binotti, Benjamin Dombert, Peter Heimann, Angel Perez-Lara, Carsten Slotta, Nadine Thau-Habermann, Cora R. Von Collenberg, Franziska Karl, Markus Damme, Arie Horowitz, Isabelle Maystadt, Annette Füchtbauer, Ernst-Martin Füchtbauer, Sibylle Jablonka, Robert Blum, Nurcan Üçeyler, Susanne Petri, Barbara Kaltschmidt, Reinhard Jahn, Christian Kaltschmidt, Michael Sendtner

Department of Medicine Faculty Papers

Autophagy-mediated degradation of synaptic components maintains synaptic homeostasis but also constitutes a mechanism of neurodegeneration. It is unclear how autophagy of synaptic vesicles and components of presynaptic active zones is regulated. Here, we show that Pleckstrin homology containing family member 5 (Plekhg5) modulates autophagy of synaptic vesicles in axon terminals of motoneurons via its function as a guanine exchange factor for Rab26, a small GTPase that specifically directs synaptic vesicles to preautophagosomal structures. Plekhg5 gene inactivation in mice results in a late-onset motoneuron disease, characterized by degeneration of axon terminals. Plekhg5-depleted cultured motoneurons show defective axon growth and impaired autophagy …

Decoding Critical Long Non-Coding Rna In Ovarian Cancer Epithelial-To-Mesenchymal Transition., Ramkrishna Mitra, Xi Chen, Evan J. Greenawalt, Ujjwal Maulik, Wei Jiang, Zhongming Zhao, Christine M. Eischen

Department of Cancer Biology Faculty Papers

Long non-coding RNA (lncRNA) are emerging as contributors to malignancies. Little is understood about the contribution of lncRNA to epithelial-to-mesenchymal transition (EMT), which correlates with metastasis. Ovarian cancer is usually diagnosed after metastasis. Here we report an integrated analysis of >700 ovarian cancer molecular profiles, including genomic data sets, from four patient cohorts identifying lncRNA DNM3OS, MEG3, and MIAT overexpression and their reproducible gene regulation in ovarian cancer EMT. Genome-wide mapping shows 73% of MEG3-regulated EMT-linked pathway genes contain MEG3 binding sites. DNM3OS overexpression, but not MEG3 or MIAT, significantly correlates to worse overall patient survival. DNM3OS knockdown results in …

Silent Sentence Completion Shows Superiority Localizing Wernicke's Area And Activation Patterns Of Distinct Language Paradigms Correlate With Genomics: Prospective Study., Kamel El Salek, Islam S. Hassan, Aikaterini Kotrotsou, Srishti Abrol, Scott H. Faro, Feroze B. Mohamed, Pascal O. Zinn, Wei Wei, Nan Li, Ashok J. Kumar, Jeffrey S. Weinberg, Jeffrey S. Wefel, Shelli R. Kesler, Ho-Ling Anthony Liu, Ping Hou, R. Jason Stafford, Sujit Prabhu, Raymond Sawaya, Rivka R. Colen

Department of Radiology Faculty Papers

Preoperative mapping of language areas using fMRI greatly depends on the paradigms used, as different tasks harness distinct capabilities to activate speech processing areas. In this study, we compared the ability of 3 covert speech paradigms: Silent Sentence Completion (SSC), category naming (CAT) and verbal fluency (FAS), in localizing the Wernicke's area and studied the association between genomic markers and functional activation. Fifteen right-handed healthy volunteers and 35 mixed-handed patients were included. We focused on the anatomical areas of posterosuperior, middle temporal and angular gyri corresponding to Wernicke's area. Activity was deemed significant in a region of interest if P < 0.05. Association between fMRI activation and genomic mutation status was obtained. Results demonstrated SSC's superiority at localizing Wernicke's area. SSC demonstrated functional activity in 100% of cancer patients and healthy volunteers; which was significantly higher than those for FAS and CAT. Patients with 1p/19q non-co-deleted had higher extent of activation on SSC (P < 0.02). Those with IDH-1 wild-type were more likely to show no activity on CAT (P < 0.05). SSC is a robust paradigm for localizing Wernicke's area, making it an important clinical tool for function-preserving surgeries. We also found a correlation between tumor genomics and functional activation, which deserves more comprehensive study.

Idiopathic Nodular Glomerulosclerosis In A Chronic Marijuana User; A Case Report And Review Of The Literature, Mehri Mollaee, Tibor Fülöp, Sohil Abdul Salim, Seyed Mehrdad Hamrahian

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Nodular glomerulosclerosis is a characteristic histological finding of diabetic nephropathy (DN) with thickened glomerular basement membrane (GBM) and hyalinized arterioles. Idiopathic nodular glomerulosclerosis (ING), a rare distinct clinicopathologic entity, is the term used to denote classic DN confirmed by light microscopy, immuno-fluorescence, and electron microscopy in the absence of diabetes mellitus (DM). ING has been linked to heavy tobacco smoking, chronic hypertension, obesity and insulin resistance. Its association with marijuana use is unknown. Case Presentation: We report a case of biopsy-proved ING in the absence of pre-existing history of DM and heavy smoking. This report addresses the possible accentuation …

How Should Clinicians Weigh The Benefits And Harms Of Discussing Politicized Topics That Influence Their Individual Patients' Health?, Diana Alame, Robert D. Truog

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Health implications of politically charged phenomena are particularly difficult for physicians to discuss with their patients and communities. Addressing climate change and its associated health effects involves trade-offs between health and economic prosperity, necessitating that physicians weigh the potential benefits and risks of discussing climate change health effects. We argue that the potential benefits of physician communication and advocacy ultimately outweigh the potential risks. Therefore, physicians should be supported in their efforts to educate their patients and communities about climate change health effects. Furthermore, democratic deliberation could prove helpful in addressing disagreements among physicians within a practice about such politicized …

Mutational Patterns In Chemotherapy Resistant Muscle-Invasive Bladder Cancer., David Liu, Philip Abbosh, Daniel Keliher, Brendan Reardon, Diana Miao, Kent Mouw, Amaro Weiner-Taylor, Stephanie Wankowicz, Garam Han, Min Yuen Teo, Catharine Cipolla, Jaegil Kim, Gopa Iyer, Hikmat Al-Ahmadie, Essel Dulaimi, David Y.T. Chen, R. Katherine Alpaugh, Jean Hoffman-Censits, Levi A. Garraway, Gad Getz, Scott L. Carter, Joaquim Bellmunt, Elizabeth R. Plimack, Jonathan E. Rosenberg, Eliezer M. Van Allen

Department of Medical Oncology Faculty Papers

Despite continued widespread use, the genomic effects of cisplatin-based chemotherapy and implications for subsequent treatment are incompletely characterized. Here, we analyze whole exome sequencing of matched pre- and post-neoadjuvant cisplatin-based chemotherapy primary bladder tumor samples from 30 muscle-invasive bladder cancer patients. We observe no overall increase in tumor mutational burden post-chemotherapy, though a significant proportion of subclonal mutations are unique to the matched pre- or post-treatment tumor, suggesting chemotherapy-induced and/or spatial heterogeneity. We subsequently identify and validate a novel mutational signature in post-treatment tumors consistent with known characteristics of cisplatin damage and repair. We find that post-treatment tumor heterogeneity predicts …

Widespread Theta Synchrony And High-Frequency Desynchronization Underlies Enhanced Cognition., E. A. Solomon, J. E. Kragel, Michael R. Sperling, Ashwini Sharan, G. Worrell, M. Kucewicz, C. S. Inman, B. Lega, K. A. Davis, J. M. Stein, B. C. Jobst, K. A. Zaghloul, S. A. Sheth, D. S. Rizzuto, M. J. Kahana

Department of Neurology Faculty Papers

The idea that synchronous neural activity underlies cognition has driven an extensive body of research in human and animal neuroscience. Yet, insufficient data on intracranial electrical connectivity has precluded a direct test of this hypothesis in a whole-brain setting. Through the lens of memory encoding and retrieval processes, we construct whole-brain connectivity maps of fast gamma (30-100 Hz) and slow theta (3-8 Hz) spectral neural activity, based on data from 294 neurosurgical patients fitted with indwelling electrodes. Here we report that gamma networks desynchronize and theta networks synchronize during encoding and retrieval. Furthermore, for nearly all brain regions we studied, …

Interaction Of Rna-Binding Protein Hur And Mir-466i Regulates Gm-Csf Expression., Jing Chen, William Adamiak, Ganlei Huang, Ulus Atasoy, Abdolmohamad M. Rostami, Shiguang Yu

Department of Neurology Faculty Papers

Granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by T helper 17 (Th17) cells plays an essential role in autoimmune diseases. Transcriptional regulation of Th17 cell differentiation has been extensively studied, but post-transcriptional regulation of Th17 cell differentiation has remained less well characterized. The RNA-binding protein HuR functions to promote the stability of target mRNAs via binding the AU-rich elements of the 3' untranslated region (3'UTR) of numerous pro-inflammatory cytokines including IL-4, IL-13, IL-17 and TNF-α. However, whether HuR regulates GM-CSF expression in Th17 cells has not been fully investigated. Here we showed that HuR conditional knockout (KO) Th17 cells have decreased GM-CSF …

Evaluation Of Perampanel As Monotherapy For Focal Seizures: Experience From Open-Label Extension Studies, Patrick Kwan, Scott Mintzer, Antonio Laurenza, Anna Patten, Karen Cartwright, Formerly: Eisai Ltd.

Department of Neurology Faculty Papers

Perampanel, a selective, non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, is approved for adjunctive treatment of focal seizures, with or without secondarily generalized seizures, and for primary generalized tonic–clonic seizures in patients with epilepsy aged ≥ 12 years. Perampanel was recently approved for monotherapy use for focal seizures in the U.S.A. Anti-seizure drug monotherapy may be preferable to polytherapy, which is generally associated with increased toxicity, non-compliance, and cost. Here, we report cases where patients had converted to perampanel monotherapy during open-label extension (OLEx) portions of 9 Phase II and III studies. Of 2245 patients who enrolled in the OLEx studies, …

Impact Of Natural Blind Spot Location On Perimetry., Mengyu Wang, Lucy Q. Shen, Michael V. Boland, Sarah R. Wellik, Carlos Gustavo De Moraes, Jonathan S. Myers, Peter J. Bex, Tobias Elze

Wills Eye Hospital Papers

We study the spatial distribution of natural blind spot location (NBSL) and its impact on perimetry. Pattern deviation (PD) values of 11,449 reliable visual fields (VFs) that are defined as clinically unaffected based on summary indices were extracted from 11,449 glaucoma patients. We modeled NBSL distribution using a two-dimensional non-linear regression approach and correlated NBSL with spherical equivalent (SE). Additionally, we compared PD values of groups with longer and shorter distances than median, and larger and smaller angles than median between NBSL and fixation. Mean and standard deviation of horizontal and vertical NBSL were 14.33° ± 1.37° and -2.06° ± …