A study of the prevalence of antibodies to Epstein-Barr virus in a large cohort of patients with early multiple sclerosis

Hintergrund: Die Multiple Sklerose (MS) ist eine entzündliche Erkrankung des zentralen Nervensystems (ZNS), die auf dem Boden einer Interaktion von genetischen und Umweltfaktoren entsteht. Der wichtigste und stärkste derzeit bekannte externe Risikofaktor für die Entwicklung einer MS ist eine Infektion mit dem Epstein-Barr-Virus (EBV). Frühere seroepidemiologische Untersuchungen haben übereinstimmend gezeigt, dass fast alle Patienten mit MS EBV-seropositiv sind. Sollte eine Infektion mit EBV tatsächlich eine Voraussetzung zur Entwicklung einer MS sein, wäre jedoch zu erwarten, dass Patienten mit MS ausnahmslos EBV-seropositiv sind. Somit stellt sich die Frage, ob es wirklich EBV-seronegative Patienten mit einer MS gibt. Zielsetzung: Zielsetzung der vorliegenden Arbeit war die Bestimmung der Seroprävalenz von Antikörpern gegen das EBV in einer großen Kohorte von Patienten mit früher MS. Methodik: In Serumproben von 901 Patienten mit einem klinisch isolierten Syndrom (KIS, der klinischen Erstmanifestation einer MS) oder schubförmiger MS aus der deutschen nationalen MS-Kohorte wurden IgG-Antikörper gegen das Epstein-Barr nukleäre Antigen-1 (EBNA-1) mit einem Chemilumineszenz-Immunoassay (CLIA) gemessen. Antikörper gegen das EBV viral capsid antigen (VCA) wurden bei EBNA-1-Antikörper-seronegativen Patienten ebenfalls mittels CLIA analysiert. EBNA-1- und VCA-Antikörper-seronegative Patienten wurden mit einem EBV-IgG-Immunoblot untersucht. Zur Ermittlung der EBV-Seroprävalenz in einer Kontrollpopulation wurde in einer großen Krankenhauspopulation (n=16.163) aus Berlin/Norddeutschland die EBV-Seroprävalenz in unterschiedlichen Altersgruppen von 80 Jahren ermittelt. Ergebnisse: Von 901 Patienten mit KIS/RRMS hatten 839 IgG-Antikörper gegen EBNA-1. IgG-Antikörper gegen VCA wurden bei 45 von 62 EBNA-1-Antikörper seronegativen Patienten nachgewiesen. Unter Verwendung von EBV-IgG-Immunoblots wurden bei allen übrigen 17 Patienten IgG-Antikörper gegen EBV gefunden. Somit waren alle 901 Patienten (100%) mit KIS/RRMS, die in unsere Studie eingeschlossen wurden, seropositiv für EBV. Die EBV-Seroprävalenz in der Krankenhauspopulation stieg mit zunehmendem Alter in allen 5-Jahres-Alterskohorten an, erreichte aber in keiner der untersuchten Altersgruppen 100%. Schlussfolgerungen: Die Abwesenheit von EBV-seronegativen Personen in dieser gut charakterisierten Kohorte von Patienten mit früher MS weist auf eine zentrale Rolle von EBV bei der MS hin. Eine negative EBV-Serologie bei Patienten mit Verdacht auf eine entzündliche Erkrankung des ZNS spricht gegen eine MS und sollte anderweitige Diagnosen in Betracht ziehen lassen.Background: Multiple Sclerosis (MS) is an inflammatory disease of the central nervous system, which develops through an interaction of genetic and environmental factors. Epstein-Barr virus (EBV) is the most important and strongest currently known risk factor for MS. Previous seroepidemiological studies have consistently shown that almost all patients with MS are EBV-seropositive. However, if EBV infection was indeed a prerequisite for development of MS, one would expect that all patients with MS (100%) would be EBV seropositive. The question therefore arises whether EBV seronegative patients with MS do really exist. Objective: The present study aimed to determine the seroprevalence of antibodies against EBV in a large cohort of patients with early MS. Methods: In serum samples from 901 patients with a clinically isolated syndrome (CIS, the first clinical manifestation of multiple sclerosis) or with early relapsing-remitting MS (RRMS) from the German National MS cohort antibodies to Epstein-Barr nuclear antigen-1 (EBNA-1) were measured by a chemiluminescence immunoassay (CLIA). Antibodies to the EBV viral capsid antigen (VCA) were analyzed in EBNA-1 antibody seronegative patients by CLIA as well. EBV IgG immunoblot was used to analyze EBNA-1 and VCA antibody seronegative patients. To determine the EBV seroprevalence in a control population, we determined the EBV seroprevalence in different age groups ranging from 80 years in a large hospital population (n = 16,163) from Berlin/Northern Germany. Results: Of the 901 patients with CIS/RRMS, 839 had IgG antibodies to EBNA-1. IgG antibodies to VCA were detected in 45 of 62 EBNA-1 antibody seronegative patients. Using EBV IgG immunoblots, IgG antibodies to EBV were found among all the remaining 17 patients. Therefore, all 901 patients (100%) with CIS/RRMS included in our study were seropositive for EBV. EBV seropositivity increased with increasing age in the hospital population, but did not reach 100% in any of the examined age groups. Conclusions: The absence of EBV seronegativity in this well-characterized cohort of patients with early MS indicates a central role of EBV in MS. EBV seronegativity in patients with suspected inflammatory central nervous system diseases should alert clinicians to take into account diagnoses other than MS

Dominant Periods of Expected Ground Motion of Gyumri Territory by a Method of Calculating Dominant Periods in Non-Homogenous Surface Layers of the Earth\u27s Crust

The seismoresistance of buildings and constructions is substantially connected by the regularity of the ground vibrations during the strong earthquakes. The main character of any vibration is its highness of component periods. The periods firstly depend on the environmental ground. During the strong earthquakes the precise results we can get only by a method of instrumental records. During the Spitak earthquake in 1988 with M = 7.0 in Gyumri town, which is situated 30 km far from the epicenter and had developed net of seismic stations it has been got only one record, which did not give any real imaginations about dominant periods. It’s know that many scientists and K. Kanai among came to conclusion that during the numerous earthquakes with M \u3e 6 the main periods of grounds observed coincide with the dominant periods of micro-vibrations of the environmental grounds. Using the method of calculation of dominant periods for non-homogenous surface layers and having the micro-vibration records of Gyumri town there was defined the approximate dominant periods of Gyumri territory during the expecting strong earthquakes

Opera as Statecraft in Soviet Armenia and Kazakhstan

This dissertation reconceptualizes Soviet music history by focusing on the artistic productions of ethnic and racial minorities under the Communist Party’s subjugation. According to communist propaganda, the Soviet state overthrew Russian imperialism and—as part of a cultural revolution—commissioned national operas to celebrate the diversity of each republic. I argue, however, that under the guise of modernization, the allegedly anti-colonial Communist Party used opera as a colonial technology of rule to negate difference. The Soviet national opera project thus pursued the age-old Russian imperial practices of assimilation and subjugation, which allowed communists to maintain rule over a multiethnic population. Each of the chapters focuses on one of the four intersecting axes across which the Soviet state attempted to redefine Armenian and Kazakh nationalism through opera: religious practices, historical memory, racialization, and gender norms. In addition to examining opera as an instrument of totalitarian control, as many scholars have done, a key feature of my work is the reversal of “the imperial gaze.” I propose a theory of drastic hybridity to examine how Armenian and Kazakh composers negotiated their identities in creative and subversive ways. The interdisciplinarity of this project—spanning music studies, Slavic studies, and postcolonial studies—charts new paths for remapping the geopolitics of Soviet history, which in turn allows us to understand the present-day struggle of Armenian and Kazakh peoples to decolonize their cultural identities

Comparison of Frequency Spectra for Micotremors, After Shocks (M=2.5-4.7) and the Main Shock of the Spitak Earthquake Obtained on Massive Lake-River Formations in the Region of Giumry (Armenia)

On December 7, 1988 a disastrous earthquake with magnitude M=7.0 took place in the northern part of Armenia, during which in Giumry (former Leninakan) large-scale destruction of standardized buildings with epicentral distance 35 km was observed. This forced us to set a task: to find connection between large-scale destruction and some dynamic peculiarities of grounds on the territory of the city. The present article makes an attempt to explain the significance of the upper engineering-geological stratum (20-30 m) and that of the lower massive lake-river formations. Basing ourselves on a great number of instrumental observations we tried to compare prevailing periods of ground microthremors with frequency spectra of the Spitak earthquake main shock and its aftershocks and to reveal connection between them in order to ascertain the significance of own prevailing periods of grounds on the territory of Giumry in the large-scale destruction during the main shock as well as to prove that they didn’t manifest themselves during the event. The obtained results can be applied to drawing up of new seismic microzonation maps not only for Giumry, but for an territories of other cities as well, which are situated on massive lake-river formations. Besides the results can benefit creators of normative documents on seismostable building

Estimations In Distribution And Growing Characteristics Of Wild Hypericum Perforatum L. (Hypericaceae) Populations During The Last Decade In Armenia

The small mountainous country of Armenia has a rich flora of ca. 3600 species of vascular plants, which makes about half of entire Caucasian flora, distributed across desert and semi-desert, steppe, forest and alpine landscape. Anthropogenic threats to this biodiversity such as overpopulation, deforestation and urbanization have simultaneously hindered research and increased the need for it. Of the ca. 500 species in the Armenian flora with a record of medicinal and/or economic use, ca. 50 species are used in the folk medicine and include both wild-collected (Crataegus sp., Hypericum perforatum, Artemisia absinthium) and cultivated (Chamomilla recutita, Mentha piperita, Crocus sativus) species (1). Only limited information on the genetic biodiversity, population location, structure and size, and conservation status of most of these species is, however, at this time available. During 2007-2009, field studies were conducted to re-locate populations of wild Hypericum perforatum L. (common St. Johnswort, Hypericaceae) on the basis of historical (i.e. herbarium voucher, (2)) records, and to discover new populations. The plants habitat and phenological characteristics were estimated growing in different populations. GPS map of population distribution was created and its overall sizes were assessed. According to historical records this species had been widely distributed in the south regions of Armenia, however almost half of the populations no longer existed in the cited locations. However, 2 new populations were loacated in the south east regions. Evidence that the abundance and distributional range of H. perforatum is expanding in the north region was collected. This research provided baseline data that can be used for the development of further ex situ and in vitro strategies to conserve unique genotypes of this important medicinal and culinary species in Armenia

Vortices in Rotating and Gravitating Gas Disk and in a Protoplanetary Disk

Nonlinear equations describing dynamics of 2D vortices are very important in the physics of the ocean and the atmosphere and in plasma physics and Astrophysics. Here linear and nonlinear 2D vortex perturbations of gravitating and light gaseous disks are examined in the geostrophic and post-geostrophic approximations. In the frame of geostrophic approximation, it is shown that the vortex with positive velocity circulation is characterized by low pressure with negative excess mass density of substance. Vortex with negative circulation has higher pressure and is a relatively tight formation with the positive excess mass density. In the post-geostrophic approximation, structures of the isolated monopole and dipole vortex (modons) solutions of these equations are studied. Two types of mass distributions in dipole vortices are found. The first type of modon is characterized by an asymmetrically positioned single circular densification and one rarefaction. The second type is characterized by two asymmetrically positioned densifications and two rarefactions, where the second densification-rarefaction pair is crescent shaped. The constant density contours of a dipole vortex in a light gas disk coincide with the streamlines of the vortex; in a self-gravitating disk, the constant density contours in the vortex do not coincide with streamlines. Possible manifestations of monopole and dipole vortices in astrophysical objects are discussed. Vortices play decisive role in the process of planet formation. Gas in a protoplanetary disk practically moves on sub-Keplerian speeds. Rigid particles, under the action of a head wind drags, lose the angular momentum and energy. As a result, the ~10 cm to meter-sized particles drift to the central star for hundreds of years. Long-lived vortical structures in gas disk are a possible way to concentrate the ~10 cm to meter sized particles and to grow up them in planetesimal. Here the effect of anticyclonic Burgers vortex on formation of planetesimals in a protoplanetary dusty disc in local approach is also considered. It is shown that the Burgers vortex with homogeneously rotating kernel and a converging radial stream of substance can effectively accumulate in its nuclear area the meter-sized rigid particles of total mass ∼1028 g for characteristic time ∼106 year

New Exact Solutions for Modified Burgers Vortex

Exact solutions of Navier-Stokes equation, presenting a new asymmetric vortex, in framework of modified by Shivamoggi Burgers vortex [8], has been obtained both for steady and for specific unsteady cases. The steady vortex is expressed by the function of parabolic cylinder, unsteady one is expressed by Hermit polynomials

Environmental Niche Modelling with Desktop GARP for Wild Origanum vulgare L . (Lamiaceae) in Armenia

Predicting species’ distributions has became one of the significant components of conservation biology in recent years. During the study, GARP (genetic algorithm) has been identified the key modelling technique for determining Origanum vulgare L. (Oregano, Lamiaceae) environmental niche in the Republic of Armenia. For over three consecutive years, from 2010-2013 it has been created relevant environmental layers through ESRI ArcGIS programs to be used with the plant actual distribution (occurrence records) as input data of GARP. In the result of the study, it has been produced the fundamental and realized niche and predictive habitat distribution of O. vulgare L. with Bitmap under the global climate change. Produced Bitmap illustrates that Oregano distributions would decrease mostly in the central regions due to environmental deterioration and climate change. This research could provide significant data for future conservation planning of wild Oregano in the Republic of Armenia