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Robert N Kirchdoerfer, Crystal L Moyer, Dafna M Abelson, Erica Ollmann Saphire
Filoviruses are capable of causing deadly hemorrhagic fevers. All nonsegmented negative-sense RNA-virus nucleocapsids are composed of a nucleoprotein (NP), a phosphoprotein (VP35) and a polymerase (L). However, the VP30 RNA-synthesis co-factor is unique to the filoviruses. The assembly, structure, and function of the filovirus RNA replication complex remain unclear. Here, we have characterized the interactions of Ebola, Sudan and Marburg virus VP30 with NP using in vitro biochemistry, structural biology and cell-based mini-replicon assays...
October 2016: PLoS Pathogens
Lena-Marie Kortland, Anne Alfter, Oliver Bähr, Barbara Carl, Richard Dodel, Thomas M Freiman, Kristina Hubert, Kolja Jahnke, Susanne Knake, Felix von Podewils, Jens-Peter Reese, Uwe Runge, Christian Senft, Helmuth Steinmetz, Felix Rosenow, Adam Strzelczyk
OBJECTIVE: To provide first data on inpatient costs and cost-driving factors due to nonrefractory status epilepticus (NSE), refractory status epilepticus (RSE), and super-refractory status epilepticus (SRSE). METHODS: In 2013 and 2014, all adult patients treated due to status epilepticus (SE) at the university hospitals in Frankfurt, Greifswald, and Marburg were analyzed for healthcare utilization. RESULTS: We evaluated 341 admissions in 316 patients (65...
October 18, 2016: Epilepsia
Christoph Priesner, Ruth Esser, Sabine Tischer, Michael Marburger, Krasimira Aleksandrova, Britta Maecker-Kolhoff, Hans-Gert Heuft, Lilia Goudeva, Rainer Blasczyk, Lubomir Arseniev, Ulrike Köhl, Britta Eiz-Vesper, Stephan Klöß
BACKGROUND AND AIMS: The infusion of enriched CMV-specific donor T-cells appears to be a suitable alternative for the treatment of drug-resistant CMV reactivation or de novo infection after both solid organ and hematopoietic stem cell transplantation. Antiviral lymphocytes can be selected from apheresis products using the CliniMACS Cytokine-Capture-System(®) either with the well-established CliniMACS(®) Plus (Plus) device or with its more versatile successor CliniMACS Prodigy(®) (Prodigy)...
2016: Frontiers in Immunology
Vincent Madelain, Jérémie Guedj, France Mentré, Thi Huyen Tram Nguyen, Frédéric Jacquot, Lisa Oestereich, Takumi Kadota, Koichi Yamada, Anne-Marie Taburet, Xavier de Lamballerie, Hervé Raoul
Favipiravir is a RNA polymerase inhibitor that showed a strong antiviral efficacy in vitro and in small animal models of several viruses responsible for hemorrhagic fever (HF) including Ebola virus. The aim of this work was to characterize the complex pharmacokinetics of favipiravir in non-human primates (NHP) in order to guide future efficacy studies of favipiravir in large animal models.Four different studies were conducted in 30 uninfected cynomolgus macaques of Chinese (n=17) or Mauritian (n=13) origin treated with intravenous favipiravir for 7 to 14 days with maintenance doses of 60 to 180 mg/kg BID...
October 10, 2016: Antimicrobial Agents and Chemotherapy
Ricarda Mewes, Lea Kowarsch, Hanna Reinacher, Urs M Nater
Introduction: The number of refugees and asylum seekers in Germany is high. Presumably, the need for psychotherapeutic care is high in this group. However, this need stands in contrast to a lack of a specialized and widespread provision of such care. Registered psychotherapists could help to partially reduce this gap. The present study aimed at learning more about the expected or experienced obstacles and opportunities of registered psychotherapists in regard to the psychotherapeutic treatment of asylum seekers in Germany...
September 2016: Psychotherapie, Psychosomatik, Medizinische Psychologie
Aileen E O'Hearn, Matthew A Voorhees, David P Fetterer, Nadia Wauquier, Moinya R Coomber, James Bangura, Joseph N Fair, Jean-Paul Gonzalez, Randal J Schoepp
BACKGROUND: Sub-Saharan Africa is home to a variety of pathogens, but disease surveillance and the healthcare infrastructure necessary for proper management and control are severely limited. Lassa virus, the cause of Lassa fever, a severe hemorrhagic fever in humans is endemic in West Africa. In Sierra Leone at the Kenema Government Hospital Lassa Diagnostic Laboratory, up to 70 % of acute patient samples suspected of Lassa fever test negative for Lassa virus infection. This large amount of acute undiagnosed febrile illness can be attributed in part to an array of hemorrhagic fever and arthropod-borne viruses causing disease that goes undetected and untreated...
October 3, 2016: Virology Journal
Martin Hölzer, Verena Krähling, Fabian Amman, Emanuel Barth, Stephan H Bernhart, Victor A O Carmelo, Maximilian Collatz, Gero Doose, Florian Eggenhofer, Jan Ewald, Jörg Fallmann, Lasse M Feldhahn, Markus Fricke, Juliane Gebauer, Andreas J Gruber, Franziska Hufsky, Henrike Indrischek, Sabina Kanton, Jörg Linde, Nelly Mostajo, Roman Ochsenreiter, Konstantin Riege, Lorena Rivarola-Duarte, Abdullah H Sahyoun, Sita J Saunders, Stefan E Seemann, Andrea Tanzer, Bertram Vogel, Stefanie Wehner, Michael T Wolfinger, Rolf Backofen, Jan Gorodkin, Ivo Grosse, Ivo Hofacker, Steve Hoffmann, Christoph Kaleta, Peter F Stadler, Stephan Becker, Manja Marz
The unprecedented outbreak of Ebola in West Africa resulted in over 28,000 cases and 11,000 deaths, underlining the need for a better understanding of the biology of this highly pathogenic virus to develop specific counter strategies. Two filoviruses, the Ebola and Marburg viruses, result in a severe and often fatal infection in humans. However, bats are natural hosts and survive filovirus infections without obvious symptoms. The molecular basis of this striking difference in the response to filovirus infections is not well understood...
October 7, 2016: Scientific Reports
Neetu Gupta, Romain Noël, Amélie Goudet, Karen Hinsinger, Aurélien Michau, Valérie Pons, Hajer Abdelkafi, Thomas Secher, Ayaka Shima, Olena Shtanko, Yasuteru Sakurai, Sandrine Cojean, Sébastien Pomel, Vanessa Liévin-Le Moal, Véronique Leignel, Jo-Ana Herweg, Annette Fischer, Ludger Johannes, Kate Harrison, Philippa M Beard, Pascal Clayette, Roger Le Grand, Jonathan O Rayner, Thomas Rudel, Joël Vacus, Philippe M Loiseau, Robert A Davey, Eric Oswald, Jean-Christophe Cintrat, Julien Barbier, Daniel Gillet
Medical countermeasures to treat biothreat agent infections require broad-spectrum therapeutics that do not induce agent resistance. A cell-based high-throughput screen (HTS) against ricin toxin combined with hit optimization allowed selection of a family of compounds that meet these requirements. The hit compound Retro-2 and its derivatives have been demonstrated to be safe in vivo in mice even at high doses. Moreover, Retro-2 is an inhibitor of retrograde transport that affects syntaxin-5-dependent toxins and pathogens...
October 3, 2016: Chemico-biological Interactions
Baptiste Martin, Thomas Hoenen, Bruno Canard, Etienne Decroly
This review focuses on the recent progress in our understanding of filovirus protein structure/function and its impact on antiviral research. Here we focus on the surface glycoprotein GP1,2 and its different roles in filovirus entry. We first describe the latest advances on the characterization of GP gene-overlapping proteins sGP, ssGP and Δ-peptide. Then, we compare filovirus surface GP1,2 proteins in terms of structure, synthesis and function. As they bear potential in drug-design, the discovery of small organic compounds inhibiting filovirus entry is a currently very active field...
September 14, 2016: Antiviral Research
Tadeusz Goralczyk, Katarzyna B Wojtowicz, Anetta Undas
Activated protein C resistance (APC-R) is assessed as part of thrombophilia screening, preferably in patients not taking oral anticoagulants. Rivaroxaban is known to alter some APC-R assays. To our knowledge, there have been no reports on the effect of rivaroxaban on the Russell viper venom time (RVVT)-based APC-R assay in real-life patients. In 168 consecutive outpatients suspected of having venous thromboembolism because of thrombophilia, APC-R was determined using the RVVT-based ProC Ac R assay (Siemens, Marburg, Germany)...
September 15, 2016: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
Pragya Yadav, Prasad Sarkale, Deepak Patil, Anita Shete, Prasad Kokate, Vimal Kumar, Rajlaxmi Jain, Santosh Jadhav, Atanu Basu, Shailesh Pawar, Anakkathil Sudeep, Mangesh Gokhale, Rajen Lakra, Devendra Mourya
Bat-borne viral diseases are a major public health concern among newly emerging infectious diseases which includes severe acute respiratory syndrome, Nipah, Marburg and Ebola virus disease. During the survey for Nipah virus among bats at North-East region of India; Tioman virus (TioV), a new member of the Paramyxoviridae family was isolated from tissues of Pteropus giganteus bats for the first time in India. This isolate was identified and confirmed by RT-PCR, sequence analysis and electron microscopy. A range of vertebrate cell lines were shown to be susceptible to Tioman virus...
September 9, 2016: Infection, Genetics and Evolution
Nicolae Sarbu, Robert Y Shih, Robert V Jones, Iren Horkayne-Szakaly, Laura Oleaga, James G Smirniotopoulos
White matter diseases include a wide spectrum of disorders that have in common impairment of normal myelination, either by secondary destruction of previously myelinated structures (demyelinating processes) or by primary abnormalities of myelin formation (dysmyelinating processes). The pathogenesis of many white matter diseases remains poorly understood. Demyelinating disorders are the object of this review and will be further divided into autoimmune, infectious, vascular, and toxic-metabolic processes. Autoimmune processes include multiple sclerosis and related diseases: tumefactive demyelinating lesions, Balo concentric sclerosis, Marburg and Schilder variants, neuromyelitis optica (Devic disease), acute disseminated encephalomyelitis, and acute hemorrhagic leukoencephalopathy (Hurst disease)...
September 2016: Radiographics: a Review Publication of the Radiological Society of North America, Inc
Andrea Rivera, Ilhem Messaoudi
Ebola viruses (EBOVs) and Marburg viruses (MARVs) are among the deadliest human viruses, as highlighted by the recent and widespread Ebola virus outbreak in West Africa, which was the largest and longest epidemic of Ebola virus disease (EVD) in history, resulting in significant loss of life and disruptions across multiple continents. Although the number of cases has nearly reached its nadir, a recent cluster of 5 cases in Guinea on March 17, 2016, has extended the enhanced surveillance period to June 15, 2016...
September 1, 2016: Journal of Leukocyte Biology
Daipei Liu, Herwig Peters, Steffen Marburg, Nicole Kessissoglou
Non-negative intensity is used to identify the surface areas of a structure that contributes to the scattered sound power. In the acoustic near field, the scattered sound power is predicted using non-negative intensity, as well as the scattered acoustic intensity integrated directly over the scatterer's surface area. In the acoustic far field, the scattered acoustic intensity and the scattered sound power are evaluated for three different receiver surface areas, corresponding to a sphere representing a far-field area that fully circumscribes the scatterer, and two hemispherical surfaces that correspond to partial far-field areas that do not fully circumscribe the scatterer...
August 2016: Journal of the Acoustical Society of America
Tina Stibane, Helmut Sitter, Despina Neuhof, Helena Wiechens, Andrea Schönbauer, Stefan Bösner, Erika Baum
Clinical skills such as history taking, diagnostic reasoning, therapy planning, and giving advice are even more complex than practical skills like lung auscultation and have to be applied in complex clinical situations. We judged this competence in an interdisciplinary formative OSCE conducted with students of Marburg University. Results of 218 students passing 643 OSCE stations composed of 37 different scenarios were analyzed. As a competence based examination that reflects the practical skills gained during clinical training, the here presented analysis serves also as a feedback instrument for clinical teachers, their respective disciplines and the medical faculty as a whole...
2016: GMS Journal for Medical Education
Christoph Priesner, Krasimira Aleksandrova, Ruth Esser, Nadine Mockel-Tenbrinck, Jana Leise, Katharina Drechsel, Michael Marburger, Andrea Quaiser, Lilia Goudeva, Lubomir Arseniev, Andrew Kaiser, Wolfgang Glienke, Ulrike Koehl
Multiple clinical studies demonstrated that adaptive immunotherapy using redirected T cells against advanced cancer has led to promising results with improved survival of the patients. The continuously increasing interest in those advanced Gene Therapy Medicinal Products (GTMPs) leads to a challenge on the manufacturing side regarding automation, process robustness and cell storage. Therefore, our study addresses the proof of principle in clinical-scale selection, stimulation, transduction and expansion of T cells using the automated closed CliniMACS® Prodigy system...
August 25, 2016: Human Gene Therapy
Toni Rieger, Romy Kerber, Hussein El Halas, Elisa Pallasch, Sophie Duraffour, Stephan Günther, Stephan Ölschläger
BACKGROUND:  Diagnosis of Ebola virus (EBOV) disease (EVD) requires laboratory testing. METHODS:  The RealStar Filovirus Screen reverse transcription-polymerase chain reaction (RT-PCR) kit and the derived RealStar Zaire Ebolavirus RT-PCR kit were validated using in vitro transcripts, supernatant of infected cell cultures, and clinical specimens from patients with EVD. RESULTS:  The Filovirus Screen kit detected EBOV, Sudan virus, Taï Forest virus, Bundibugyo virus, Reston virus, and Marburg virus and differentiated between the genera Ebolavirus and Marburgvirus The amount of filovirus RNA that could be detected with a probability of 95% ranged from 11 to 67 RNA copies/reaction on a LightCycler 480 II...
October 15, 2016: Journal of Infectious Diseases
Britney Johnson, Jing Li, Jagat Adhikari, Megan R Edwards, Hao Zhang, Toni Schwarz, Daisy W Leung, Christopher F Basler, Michael L Gross, Gaya K Amarasinghe
Marburg virus (MARV), a member of the Filoviridae family that also includes Ebola virus (EBOV), causes lethal hemorrhagic fever with case fatality rates that have exceeded 50% in some outbreaks. Within an infected cell, there are numerous host-viral interactions that contribute to the outcome of infection. Recent studies identified MARV protein 24 (mVP24) as a modulator of the host antioxidative responses, but the molecular mechanism remains unclear. Using a combination of biochemical and mass spectrometry studies, we show that mVP24 is a dimer in solution that directly binds to the Kelch domain of Kelch-like ECH-associated protein 1 (Keap1) to regulate nuclear factor (erythroid-derived 2)-like 2 (Nrf2)...
August 28, 2016: Journal of Molecular Biology
Andrea Marzi, Patrick W Hanley, Elaine Haddock, Cynthia Martellaro, Gary Kobinger, Heinz Feldmann
The Ebola virus (EBOV) epidemic in West Africa increased the focus on vaccine development against this hemorrhagic fever-causing pathogen, and as a consequence human clinical trials for a few selected platforms were accelerated. One of these vaccines is vesicular stomatitis virus (VSV)-EBOV, also known as rVSV-ZEBOV, a fast-acting vaccine against EBOV and so far the only vaccine with reported efficacy against EBOV infections in humans in phase III clinical trials. In this study, we analyzed the potential of VSV-EBOV for postexposure treatment of rhesus macaques infected with EBOV-Makona...
October 15, 2016: Journal of Infectious Diseases
Elizabeth A Nelson, Alyson B Barnes, Ronald D Wiehle, Gregory K Fontenot, Thomas Hoenen, Judith M White
The 2014 outbreak of Ebola virus (EBOV) in Western Africa highlighted the need for anti-EBOV therapeutics. Clomiphene is a U.S. Food and Drug Administration (FDA)-approved drug that blocks EBOV entry and infection in cells and significantly protects EBOV-challenged mice. As provided, clomiphene is, approximately, a 60:40 mixture of two stereoisomers, enclomiphene and zuclomiphene. The pharmacokinetic properties of the two isomers vary, but both accumulate in the eye and male reproductive tract, tissues in which EBOV can persist...
2016: Viruses
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