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Effect Of Acute Administration Of Angiopoietin-1 In Experimental Traumatic Spinal Cord Injury: Magnetic Resonance Imaging And Neurobehavioral Studies, Chirag B. Patel

Dissertations and Theses (Open Access)

Spinal cord injury (SCI) is a devastating condition that affects people in the prime of their lives. A myriad of vascular events occur after SCI, each of which contributes to the evolving pathology. The primary trauma causes mechanical damage to blood vessels, resulting in hemorrhage. The blood-spinal cord barrier (BSCB), a neurovascular unit that limits passage of most agents from systemic circulation to the central nervous system, breaks down, resulting in inflammation, scar formation, and other sequelae. Protracted BSCB disruption may exacerbate cellular injury and hinder neurobehavioral recovery in SCI.

In these studies, angiopoietin-1 (Ang1), an agent known to reduce …

An Innovative Phase I Trial Design Allowing For The Identification Of Multiple Potential Maximum To Lerated Doses With Combination Therapy Of Targeted Agents, Sarina A. Piha-Paul

Dissertations and Theses (Open Access)

Treatment for cancer often involves combination therapies used both in medical practice and clinical trials. Korn and Simon listed three reasons for the utility of combinations: 1) biochemical synergism, 2) differential susceptibility of tumor cells to different agents, and 3) higher achievable dose intensity by exploiting non-overlapping toxicities to the host. Even if the toxicity profile of each agent of a given combination is known, the toxicity profile of the agents used in combination must be established. Thus, caution is required when designing and evaluating trials with combination therapies. Traditional clinical design is based on the consideration of a single …

The Efficacy Of Intravenous Hyoscine-N-Butylbromide (Buscopan®) For The Acceleration Of Labour In First Time Parturients: A Randomised, Double-Blind, Placebo-Controlled Trial, Mukaindo A. Mwaniki

Master of Medicine in Obstetrics and Gynecology

Objective: to establish the safety and efficacy of hyoscine-N-butylbromide (Buscopan®) in accelerating labour in first time parturients. Design: a randomised, double-blinded, placebo-controlled clinical trial. Setting: the antenatal clinic and maternity unit of the Aga Khan University Hospital Nairobi, Kenya. Population: first time parturients in spontaneous labour at term. Methods: women were randomised to receive 40mg of hyoscine-N-butylbromide or sterile water for injection intravenously once they were confirmed to be in active labour. The dose could be repeated once after four hours. Outcome measures: the main outcome measure was the duration of labour from diagnosis of active stage to delivery. Secondary …

Teratology Primer-2nd Edition (7/9/2010), Sura Alwan, Steven B. Bleyl, Robert L. Brent, Christina D. Chambers, George P. Daston, Elaine M. Faustman, Richard H. Finnell, F. Clarke Fraser, Jan M. Freidman, Adriane Fugh-Berman, John M. Graham, Jr., Barbara F. Hales, Deborah K. Hansen, Lewis B. Holmes, Ronald D. Hood, Robert J. Kavlock, Thomas B. Knudsen, Joseph Lary, Donald R. Mattison, Richard K. Miller, James L. Mills, Janine E. Polifka, Sonja A. Rasmussen, Bernard Robaire, John M. Rogers, Gary C. Schoenwolf, Anthony R. Scialli, Gary M. Shaw, Amar V. Singh, William Slikker, Jr., Ann P. Streissguth, Melissa S. Tassinari, Janet Uriu-Adams, Charles V. Vorhees, Elora J. Weringer

Department of Pediatrics Faculty Papers

Foreword:

What is Teratology?

“What a piece of work is an embryo!” as Hamlet might have said. “In form and moving how express and admirable! In complexity how infinite!” It starts as a single cell, which by repeated divisions gives rise to many genetically identical cells. These cells receive signals from their surroundings and from one another as to where they are in this ball of cells —front or back, right or left, headwards or tailwards, and what they are destined to become. Each cell commits itself to being one of many types; the cells migrate, combine into tissues, or …

Detection Of Extended Spectrum Beta Lactamases Genotypes And Their Association With Cephalosporin Susceptibility In Community Acquired Enterobacteriaceae Infections, Daniel W. Maina

Master of Medicine in Clinical Pathology

Background: Infections caused by Extended Spectrum Beta-Lactamases (ESBLs) producing enterobacteriaceae have become a global problem. Initially confined to the hospital set-up, they are increasingly being reported in the community. These infections are often resistant to a wide variety of B- lactams including extended spectrum cephalosporins, with clinical and epidemiological implications for healthcare systems and necessitate surveillance measures based on local data. Local information on the genotypes of ESBLs and their association with cephalosporin resistance in community acquired ESBL-producing Enterobacteriaceae isolates is scanty, hence the need for this study. Aim: To detect ESBLs genotypes and correlate these with susceptibility to cephalosporins …

Oncolog Volume 55, Number 07, July 2010, Joe Munch, Sunni Hoseman

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Refining Approaches to Thyroid Cancer: Time-proven treatments and newer biologic agents offer hope, particularly for patirnts with advanced disease.
• Thyroid Cancer in Children.
• Compass Summer 2010: Locoregional Cancer of the Esophagus: Timimg Surgery and Other Therapies for Resectable Disease.
• HOUSE CALL: Understanding Clinical Trials

Gsk-3alpha Directly Regulates Beta-Adrenergic Signaling And The Response Of The Heart To Hemodynamic Stress In Mice., Jibin Zhou, Hind Lal, Xiongwen Chen, Xiying Shang, Jianliang Song, Yingxin Li, Risto Kerkela, Bradley W Doble, Katrina Macaulay, Morgan Decaul, Walter J Koch, John Farber, James Woodgett, Erhe Gao, Thomas Force

Center for Translational Medicine Faculty Papers

The glycogen synthase kinase-3 (GSK-3) family of serine/threonine kinases consists of 2 highly related isoforms, alpha and beta. Although GSK-3beta has an important role in cardiac development, much remains unknown about the function of either GSK-3 isoform in the postnatal heart. Herein, we present what we believe to be the first studies defining the role of GSK-3alpha in the mouse heart using gene targeting. Gsk3a(-/-) mice over 2 months of age developed progressive cardiomyocyte and cardiac hypertrophy and contractile dysfunction. Following thoracic aortic constriction in young mice, we observed enhanced hypertrophy that rapidly transitioned to ventricular dilatation and contractile dysfunction. …

Histamine Reduces Flash Sensitivity Of On Ganglion Cells In The Primate Retina, Nikolay P Akimov, David W Marshak, Laura J Frishman, Randolph D Glickman, Rafail G Yusupov

Faculty, Staff and Student Publications

PURPOSE. In Old World primates, the retina receives input from histaminergic neurons in the posterior hypothalamus. They are a subset of the neurons that project throughout the central nervous system and fire maximally during the day. The contribution of these neurons to vision, was examined by applying histamine to a dark-adapted, superfused baboon eye cup preparation while making extracellular recordings from peripheral retinal ganglion cells. METHODS. The stimuli were 5-ms, 560-nm, weak, full-field flashes in the low scotopic range. Ganglion cells with sustained and transient ON responses and two cell types with OFF responses were distinguished; their responses were recorded …

Department Of Radiology-Annual Executive Summary Report-July 1, 2009 To June 30, 2010, Vijay M. Rao, Md

Department of Radiology Administrative Documents and Reports

86 page Annual Executive Summary Report from Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, United States

Table of Contents:

Department of Radiology

Chairman, Vice Chairmen 1

Divisions and Directors 1

Committees and Chairmen 1

Radiology Department Faculty Rank 2

Faculty with Secondary Appointments 3

Clinical Divisions 4

Radiology Residents and Fellows 5

Department Organizational Chart 6

Department Administration Chart 7

State of the Department 8

Appendix I: Publications Journal Articles 21

Books and Book Chapters 28

Abstracts 30

Appendix II: Formal Scientific Presentations 39

Appendix III: Honors, Editorial Activities, Service to Regional or National Organizations 59

Appendix IV: …

Patterns Of Fatal Gunshot Injuries In Nairobi: A Prospective Forensic Study, Ancent K. Nzioka

Master of Medicine in Anatomic Pathology

Introduction: Gunshot injuries are one of the leading causes of fatal and non fatal injury in many countries (1) .All over the world, injury studies show an increasing preference for the gun as the weapon of choice for homicides and suicides (2).Firearms are more lethal compared to other portable and concealable weapons (2). Gunshot injuries impact severely on the criminal justice as well as health care systems (3, 4). There is no available published statistics on fatal gunshot injuries inKenya. Some basic statistics are important in understanding the magnitude and severity of the socio-economic burden caused by gunshot injuries. Objective: …

Expression Patterns Of Β–Catenin, Cox-2 And P27 In Colorectal Carcinomas At Aga Khan University Hospital, Nairobi, Patricia Okiro

Master of Medicine in Anatomic Pathology

Introduction: Colorectal cancer is the third most common cancer worldwide, as indicated by WHO. Local published and unpublished data indicate that patients in the developing world with colorectal cancer tend to present at an early age, and possibly at a more advanced stage than described in the developed world. The reason for this difference is unclear, and as yet undefined. The Wnt/APC pathway, Microsatellite instability pathway and the Epigenetic pathway are three pathogenetically distinct pathways that have been implicated in the development of colorectal cancer. Exploration of these patterns may allow us to elucidate possible reasons for these differences. Objectives: …

Is Phonophobia Associated With Cutaneous Allodynia In Migraine?, Avi Ashkenazi, Irene Yang, Aamir Mushtaq, Michael L. Oshinsky

Department of Neurology Faculty Papers

ABSTRACT

Objective

To determine whether phonophobia and dynamic mechanical (brush) allodynia are associated in episodic migraine (EM).

Methods

Adult patients with EM were prospectively recruited. A structured questionnaire was used to obtain demographic and migraine related data. Phonophobia was tested quantitatively using a real time sound processor and psychoacoustic software. Sound stimuli were pure tones at frequencies of 1000 Hz, 4000 Hz and 8000 Hz, delivered to both ears at increasing intensities, until an aversive level was reached. Allodynia was assessed by brushing the patient’s skin with a gauze pad at different areas. Patients were tested both between and during …

High-Throughput Experimental Studies To Identify Mirna Targets Directly, With Special Focus On The Mammalian Brain, Peter T. Nelson, Marianthi Kiriakidou, Zissimos Mourelatos, Grace S. Tan, Mary H. Jennings, Kevin Xie, Wang-Xia Wang

Pathology and Laboratory Medicine Faculty Publications

We review the pertinent literature on methods used in high-throughput experimental identification of microRNA (miRNA) "targets" with emphasis on neurochemical studies. miRNAs are short regulatory noncoding RNAs that play important roles in the mammalian brain. The functions of miRNAs are related to their binding of RNAs including mRNAs. Since mammalian miRNAs tend to bind to target mRNAs via imperfect complementarity, understanding exactly which target mRNAs are recognized by which specific miRNAs is a challenge. Based on early experimental evidence, a set of "binding rules" for miRNAs has been described. These have focused on the 5' "seed" region of miRNAs binding …

Pulmonary Hypertension Is A Frequent Event In Patients With Chronic Myeloid Leukemia Treated With Tyrosine Kinase Inhibitors, Sameh Gaballa, Aref Al-Kali, Hagop Kantarjian, Elias Jabbour, Alfonso Quintas-Cardama, Mohamad Ayoubi, Gautam Borthakur, S. M. O'Brien, J. E. Cortes

Division of Internal Medicine Faculty Papers & Presentations

Poster presented at American Society of Clinical Oncology in Chicago Illinois.

Background:  Tyrosine kinase inhibitors (TKI) are the current standard therapy for patients with chronic myeloid leukemia (CML). Fluid retention and pleural effusions have been reported in patients treated with TKIs, particularly with dasatinib. Although TKIs have been shown to reverse pulmonary hypertension (PH) in animal models, there have been some reports of development of reversible PH with dasatinib.

Methods:  We conducted a retrospective analysis on 401 patients diagnosed with CML in chronic phase (CP) who were treated with TKIs (imatinib, dasatinib, or nilotinib) as initial therapy for CML and …

Mitochondria-Centric Activation Induced Cell Death Of Cytolytic T Lymphocytes And Its Implications For Cancer Immunotherapy, Arvind Chhabra

UCHC Articles - Research

Premature death of the adoptively transferred cytolytic T lymphocytes (CTL) by means of activation induced cell death (AICD) represents one of the major constraints in devising an effective anti-cancer immune intervention strategy. Understanding the mechanism of AICD is, therefore, critical for developing methods to interfere with this death process. Although the existing paradigm on AICD centers around the initiation of the cascade of events originating from the engagement of death receptors leading to the activation of effector caspases and eventually resulting in cell death, recent findings have questioned the universal role of caspases as the cell death executioners. We here …

Notch1 Functions As A Tumor Suppressor In A Model Of K-Ras–Induced Pancreatic Ductal Adenocarcinoma, Linda Hanlon, Jacqueline L Avila, Renée M Demarest, Scott Troutman, Megan Allen, Francesca Ratti, Anil K Rustgi, Ben Z Stanger, Fred Radtke, Volkan Adsay, Fenella Long, Anthony J Capobianco, Joseph L Kissil

Rowan-Virtua School of Osteopathic Medicine Departmental Research

K-ras is the most commonly mutated oncogene in pancreatic cancer and its activation in murine models is sufficient to recapitulate the spectrum of lesions seen in human pancreatic ductal adenocarcinoma (PDAC). Recent studies suggest that Notch receptor signaling becomes reactivated in a subset of PDACs, leading to the hypothesis that Notch1 functions as an oncogene in this setting. To determine whether Notch1 is required for K-ras-induced tumorigenesis, we used a mouse model in which an oncogenic allele of K-ras is activated and Notch1 is deleted simultaneously in the pancreas. Unexpectedly, the loss of Notch1 in this model resulted in increased …

Physiologically Based Pharmacokinetics Of Molecular Imaging Nanoparticles For Mrna Detection Determined In Tumor-Bearing Mice., Armin W Opitz, Eric Wickstrom, Mathew L Thakur, Norman J Wagner

Kimmel Cancer Center Faculty Papers

Disease detection and management might benefit from external imaging of disease gene mRNAs. Previously we designed molecular imaging nanoparticles (MINs) based on peptide nucleic acids complementary to cancer gene mRNAs. The MINs included contrast agents and analogs of insulin-like growth factor 1 (IGF-1). Analysis of MIN tumor uptake data showed stronger binding in tumors than in surrounding tissues. We hypothesized that MINs with an IGF-1 analog stay in circulation by binding to IGF-binding proteins. To test that hypothesis, we fit the tissue distribution results of several MINs in xenograft-bearing mice to a physiological pharmacokinetics model. Fitting experimental tissue distribution data …

Oncolog Volume 55, Number 06, June 2010, John Lebas

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• The BATTLE Results Are IN: Phase II trial reveals molecular signatures in lung cancer that may guide treatment decisions.
• Endoscopic Repair of Colon Perforations: Nonsurgical techniques for closing gestrointestinal defects may yiels benefits for patients undergoing colonoscopy.
• INBRIEF: Stem Cells Seen Repairing Heart Attack Damage Over Time/Additional Blood Data May Improve Pediatric Leukemia Predictions/Pediatric Patients with Rare Tumor May benefit from Heated Chemotherapy/New Findings Refute Link Between UVA, Melanoma.
• HOUSE CALL: Skin Cancer Screening: What is It and Who Should Get It ?: Types of skin cancer/Who should be screened ?/What to expect/Self-examination: Check your skin regularly and tell your …

Vampirism, Vampire Cults And The Teenager Of Today, Megan White, Hatim A. Omar

Pediatrics Faculty Publications

The aim of this paper is to summarize the limited literature on clinical vampirism, vampire cults and the involvement of adolescents in vampire-like behavior. The various definitions of clinical vampirism are outlined and the emergence of vampire cults from Gothic culture is examined. Further, the clinical features of cult behavior, the attraction to cults, the risk factors for cult involvement, and the clinical management of cult members are discussed. Additionally, vampire popular media is briefly introduced and a case study presented.

Prostaglandin E(2) Is Crucial In The Response Of Podocytes To Fluid Flow Shear Stress., Tarak Srivastava, Ellen T. Mccarthy, Ram Sharma, Patricia A. Cudmore, Mukut Sharma, Mark L. Johnson, Lynda F. Bonewald

Manuscripts, Articles, Book Chapters and Other Papers

Podocytes play a key role in maintaining and modulating the filtration barrier of the glomerulus. Because of their location, podocytes are exposed to mechanical strain in the form of fluid flow shear stress (FFSS). Several human diseases are characterized by glomerular hyperfiltration, such as diabetes mellitus and hypertension. The response of podocytes to FFSS at physiological or pathological levels is not known. We exposed cultured podocytes to FFSS, and studied changes in actin cytoskeleton, prostaglandin E(2) (PGE(2)) production and expression of cyclooxygenase-1 and-2 (COX-1, COX-2). FFSS caused a reduction in transversal F-actin stress filaments and the appearance of cortical actin …

Association Between Obesity, Depression, And Inflammation Among Seventh-Day Adventists In The Biopsychosocial Religion And Health Study, Michael Paalani

Loma Linda University Electronic Theses, Dissertations & Projects

The effects of obesity and depression on morbidity and mortality may be mediated by inflammatory processes. Homeostasis within the immune system depends on a balance of pro-inflammatory and anti-inflammatory cytokine molecules, so chronic inflammatory diseases may result from cytokine dysregulation. The target population consisted of 508 Seventh Day Adventists (SDAs) who participated in the Biopsychosocial Religion and Health Study (BHRS), a sub-study of the Adventist Health Study-2. The study was a cross-sectional analysis of the association between obesity, depression, and inflammation after controlling for demographic, socioeconomic, health behavioral, and health status variables among BHRS participants.

Obesity was assessed by body …

Ricin B Chain-Insulin Fusion Protein Immunomodulation Of Type 1 Diabetes, James Edward Carter Iii

Loma Linda University Electronic Theses, Dissertations & Projects

Type 1 diabetes mellitus (T1D) is a debilitating chronic inflammatory disease of the insulin-producing pancreatic islet β-cells that results from a combination of genetic and environmental factors. Attempts to suppress Th1-mediated autoimmune diseases such as T1D by mucosal delivery of autoantigens for immunotolerization have yielded only partial success. Attainment of satisfactory levels of sustained immunological tolerance remains to be accomplished. To restore self-tolerance requires delivery of sufficient amounts of autoantigen to stimulate regulatory T helper cells that function to survey the gut and induce tolerance to consumed antigens such as food. Oral delivery of autoantigens has previously been shown to …

Bone Density Measurement Via Radiographic Calibration, Amber Jean Bowen

Master's Theses

Musculoskeletal injuries are the most common injuries sustained by athletes and military recruits and can result in decreased performance and lifelong disability. So common and costly are these injuries that the American Academy of Orthopedic Surgeons has provided guidelines for future research, including recommendations for the development of a large animal model of bone injury (USDA 2001). In human and veterinary medicine, digital radiography represents the primary diagnostic tool the physician uses to diagnose skeletal injury. Advances in digital radiography have provided the veterinarian with opportunities to make both simple and complex radiographic assessments. We investigated a simple quantitative measurement …

Regulation Of Pim1 Under Hypoxia In Prostate Cancer, Eva Sahakian

Loma Linda University Electronic Theses, Dissertations & Projects

A defining characteristic of solid tumors is the capacity to divide and spread under conditions of nutrient deprivation and limited oxygen availability. These microenvironmental stresses arise from structural abnormalities in tumor vessels that lead to aberrant microcirculation. Hypoxia acts as a physiological “selection pressure” in the progression of cancer by activating pathways and enhancing the expression of specific genes in tumor cells which eventually diminish their apoptotic potential. Ultimately, hypoxic microenvironment functions as a “stress factor”, selecting cells with the ability to survive and divide under anoxic conditions. The members of the PIM family of cytoplasmic serine threonine kinases are …

A Direct Role For Secretory Phospholipase A2 And Lyso-Phosphatidylcholine In The Mediation Of Lipopolysaccharide-Induced Gastric Injury, Elizabeth J Dial, Duy M Tran, Jimmy J Romero, Mayssa Zayat, Lenard M Lichtenberger

Faculty, Staff and Student Publications

Endotoxemia from sepsis can injure the gastrointestinal tract through mechanisms that have not been fully elucidated. We have shown that LPS induces an increase in gastric permeability in parallel with the luminal appearance of secretory phospholipase A2 (sPLA2) and its product, lysophosphatidylcholine (lyso-PC). We proposed that sPLA2 acted on the gastric hydrophobic barrier, composed primarily of phosphatidylcholine (PC), to degrade it and produce lyso-PC, an agent that is damaging to the mucosa. In the present study, we have tested whether lyso-PC and/or sPLA2 have direct damaging effects on the hydrophobic barriers of synthetic and mucosal surfaces. Rats were administered LPS …

Organic Cation Transporter Preferentially Expressed In Hematopoietic Cells And Leukemias And Uses Thereof, Jeffrey A. Moscow, Xin Lu, Craig Jordan

Markey Cancer Center Faculty Patents

A novel organic cation transporter (OCT) gene, OCT 6, and use thereof is described. The OCT6 gene is preferentially expressed in human hematopoietic tissues, including CD34+ cells and leukemia cells. Its narrow tissue distribution, substrate specificity, and close homology to other cell membrane transporters make OCT6 an attractive target for the treatment of myeloid diseases.

Inhibition Of Abcb1 (Mdr1) Expression By An Sirna Nanoparticulate Delivery System To Overcome Drug Resistance In Osteosarcoma, Michiro Susa, Arun K. Iyer, Keinosuke Ryu, Edwin Choy, Francis J. Hornicek, Henry Mankin, Lara Milane, Mansoor M. Amiji, Zhenfeng Duan

Pharmaceutical Sciences Faculty Publications

Background: The use of neo-adjuvant chemotherapy in treating osteosarcoma has improved patients’ average 5 year survival rate from 20% to 70% in the past 30 years. However, for patients who progress after chemotherapy, its effectiveness diminishes due to the emergence of multi-drug resistance (MDR) after prolonged therapy.

Methodology/Principal Findings: In order to overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure resulting from MDR, we designed and evaluated a novel drug delivery system for MDR1 siRNA delivery. Novel biocompatible, lipid-modified dextran-based polymeric nanoparticles were used as the platform for MDR1 siRNA delivery; and the efficacy …

Cd4 T-Cell Suppression By Cells From Toxoplasma Gondii-Infected Retinas Is Mediated By Surface Protein Pd-L1, Elizabeth Charles, Sunil Joshi, John D. Ash, Barbara A. Fox

Dartmouth Scholarship

In the inflamed retina, CD4(+) T cells can cause retinal damage when they are not properly regulated. Since tissue expression of major histocompatibility complex (MHC) class II and costimulatory molecules is a key mechanism for regulating effector T cells, we tested the hypothesis that upregulation of these proteins in the retina contributes to the regulation of CD4 T cells. Here we report that in retinas infected with the protozoan parasite Toxoplasma gondii, MHC class II is upregulated on infiltrating leukocytes as well as on resident retinal cells, including photoreceptors. Flow cytometric analysis indicated that B7 costimulatory family members (CD80, CD86, …

Commencement, Georgia (2010), Philadelphia College Of Osteopathic Medicine

Commencements

Georgia Campus Commencement program, Class of 2010. Degrees include Doctorate in Osteopathic Medicine and Master of Science in Biomedical Sciences.

Thoracic Aortic Disease In Tuberous Sclerosis Complex: Molecular Pathogenesis And Potential Therapies In Tsc2+/- Mice, Jiumei Cao, Limin Gong, Dong-Chuan Guo, Ulrike Mietzsch, Shao-Qing Kuang, Callie S Kwartler, Hazim Safi, Anthony Estrera, Michael J Gambello, Dianna M Milewicz

Faculty, Staff and Student Publications

Tuberous sclerosis complex (TSC) is a genetic disorder with pleiotropic manifestations caused by heterozygous mutations in either TSC1 or TSC2. One of the less investigated complications of TSC is the formation of aneurysms of the descending aorta, which are characterized on pathologic examination by smooth muscle cell (SMC) proliferation in the aortic media. SMCs were explanted from Tsc2(+/-) mice to investigate the pathogenesis of aortic aneurysms caused by TSC2 mutations. Tsc2(+/-) SMCs demonstrated increased phosphorylation of mammalian target of rapamycin (mTOR), S6 and p70S6K and increased proliferation rates compared with wild-type (WT) SMCs. Tsc2(+/-) SMCs also had reduced expression of …