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Gary Wong, Wen-Guang Cao, Shi-Hua He, Zi-Rui Zhang, Wen-Jun Zhu, Estella Moffat, Hideki Ebihara, Carissa Embury-Hyatt, Xiang-Guo Qiu
The Angolan strain of Marburg virus (MARV/Ang) can cause lethal disease in humans with a case fatality rate of up to 90%, but infection of immunocompetent rodents do not result in any observable symptoms. Our previous work includes the development and characterization of a MARV/Ang variant that can cause lethal disease in mice (MARV/Ang-MA), with the aim of using this tool to screen for promising prophylactic and therapeutic candidates. An intermediate animal model is needed to confirm any findings from mice studies before testing in the gold-standard non-human primate (NHP) model...
January 18, 2018: Zoological Research
R Wirth, R Diekmann, G Janssen, O Fleiter, L Fricke, A Kreilkamp, M K Modreker, C Marburger, S Nels, M Pourhassan, R Schaefer, H-P Willschrei, D Volkert
Refeeding syndrome is a life-threatening complication that may occur after initiation of nutritional therapy in malnourished patients, as well as after periods of fasting and hunger. Refeeding syndrome can be effectively prevented and treated if its risk factors and pathophysiology are known. The initial measurement of thiamine level and serum electrolytes, including phosphate and magnesium, their supplementation if necessary, and a slow increase in nutritional intake along with close monitoring of serum electrolytes play an important role...
March 2, 2018: Der Internist
Elisabeth K Nyakatura, Samantha E Zak, Anna Z Wec, Daniel Hofmann, Sergey Shulenin, Russell R Bakken, M Javad Aman, Kartik Chandran, John M Dye, Jonathan R Lai
Filoviruses (family Filoviridae ) include five ebolaviruses and Marburg virus. These pathogens cause a rapidly progressing and severe viral disease with high mortality rates (generally 30%-90%). Outbreaks of filovirus disease are sporadic and, until recently, were limited to less than 500 cases. However, the 2013-2016 epidemic in western Africa, caused by Ebola virus (EBOV), illustrated the potential of filovirus outbreaks to escalate to a much larger scale (over 28,000 suspected cases). Monoclonal antibodies (mAbs) against the envelope glycoprotein represent a promising therapeutic platform for managing filovirus infections...
March 2, 2018: Journal of Biological Chemistry
Xin Zhang, Qiang Liu, Na Zhang, Qian-Qian Li, Zhan-Dong Liu, Ying-Hong Li, Li-Mei Gao, You-Chun Wang, Hong-Bin Deng, Dan-Qing Song
Preventing filoviruses in the entry stage is an attractive antiviral strategy. Taking aloperine, a Chinese natural herb with an endocyclic skeleton, as the lead, 23 new aloperine derivatives were synthesized and evaluated for their anti-filovirus activities including ebola virus (EBOV) and marburg virus (MARV) using pseudotyped virus model. Structure-activity relationship (SAR) analysis indicated that the introduction of a 12N-dichlorobenzyl group was beneficial for the potency. Compound 2e exhibited the most potent anti-EBOV and anti-MARV effects both in vitro and in vivo...
February 26, 2018: European Journal of Medicinal Chemistry
M Pourhassan, I Cuvelier, I Gehrke, C Marburger, M K Modreker, D Volkert, H P Willschrei, R Wirth
OBJECTIVES: The incidence of refeeding syndrome (RFS) in older patients is not well-known. The aim of the study was to determine the prevalence of known risk factors for RFS in older individuals during hospitalization at geriatric hospital departments. DESIGN AND SETTING: 342 consecutive older participants (222 females) who admitted at acute geriatric hospital wards were included in a cross-sectional study. We applied the National Institute for Health and Clinical Excellence (NICE) criteria for determining patients at risk of RFS...
2018: Journal of Nutrition, Health & Aging
Thomas Karr, Larry B Stotts, Jason A Tellez, Jason D Schmidt, Justin D Mansell
The propagation of high peak-power laser beams in real atmospheres will be affected at long range by both linear and nonlinear effects contained therein. Arguably, J. H. Marburger is associated with the mathematical characterization of this phenomenon. This paper provides a validated set of engineering equations for characterizing the self-focusing distance from a laser beam propagating through non-turbulent air with, and without, loss as well as three source configurations: (1) no lens, (2) converging lens and (3) diverging lens...
February 19, 2018: Optics Express
Benoit Callendret, Jort Vellinga, Kerstin Wunderlich, Ariane Rodriguez, Robin Steigerwald, Ulrike Dirmeier, Cedric Cheminay, Ariane Volkmann, Trevor Brasel, Ricardo Carrion, Luis D Giavedoni, Jean L Patterson, Chad E Mire, Thomas W Geisbert, Jay W Hooper, Mo Weijtens, Jutta Hartkoorn-Pasma, Jerome Custers, Maria Grazia Pau, Hanneke Schuitemaker, Roland Zahn
The search for a universal filovirus vaccine that provides protection against multiple filovirus species has been prompted by sporadic but highly lethal outbreaks of Ebolavirus and Marburgvirus infections. A good prophylactic vaccine should be able to provide protection to all known filovirus species and as an upside potentially protect from newly emerging virus strains. We investigated the immunogenicity and protection elicited by multivalent vaccines expressing glycoproteins (GP) from Ebola virus (EBOV), Sudan virus (SUDV), Taï Forest virus (TAFV) and Marburg virus (MARV)...
2018: PloS One
Logan Banadyga, Gary Wong, Xiangguo Qiu
The development of novel therapeutics and vaccines to treat or prevent disease caused by filoviruses, such as Ebola and Marburg viruses, depends on the availability of animal models that faithfully recapitulate clinical hallmarks of disease as it is observed in humans. In particular, small animal models (like mice and guinea pigs) are historically and frequently used for the primary evaluation of antiviral countermeasures, prior to testing in nonhuman primates, which represent the gold-standard filovirus animal model...
February 19, 2018: ACS Infectious Diseases
Arinjay Banerjee, Vikram Misra, Tony Schountz, Michelle L Baker
Bats are natural reservoirs for a variety of emerging viruses that cause significant disease in humans and domestic animals yet rarely cause clinical disease in bats. The co-evolutionary history of bats with viruses has been hypothesized to have shaped the bat-virus relationship, allowing both to exist in equilibrium. Progress in understanding bat-virus interactions and the isolation of bat-borne viruses has been accelerated in recent years by the development of susceptible bat cell lines. Viral sequences similar to severe acute respiratory syndrome corona virus (SARS-CoV) have been detected in bats, and filoviruses such as Marburg virus have been isolated from bats, providing definitive evidence for the role of bats as the natural host reservoir...
March 15, 2018: Virus Research
Sarah Marburger, Markos A Alexandrou, John B Taggart, Simon Creer, Gary Carvalho, Claudio Oliveira, Martin I Taylor
Genome size varies significantly across eukaryotic taxa and the largest changes are typically driven by macro-mutations such as whole genome duplications (WGDs) and proliferation of repetitive elements. These two processes may affect the evolutionary potential of lineages by increasing genetic variation and changing gene expression. Here, we elucidate the evolutionary history and mechanisms underpinning genome size variation in a species-rich group of Neotropical catfishes (Corydoradinae) with extreme variation in genome size-0...
February 14, 2018: Proceedings. Biological Sciences
Nadia Storm, Petrus Jansen Van Vuren, Wanda Markotter, Janusz T Paweska
Egyptian rousette bats (ERBs) are reservoir hosts for the Marburg virus (MARV). The immune dynamics and responses to MARV infection in ERBs are poorly understood, and limited information exists on the role of antibodies in protection of ERBs against MARV infection. Here, we determine the duration of maternal immunity to MARV in juvenile ERBs, and evaluate the duration of the antibody response to MARV in bats naturally or experimentally infected with the virus. We further explore whether antibodies in previously naturally exposed bats is fully protective against experimental reinfection with MARV...
February 10, 2018: Viruses
Yaroslav Winter, Naeimeh Daneshkhah, Nikolaus Galland, Isabel Kotulla, Anna Krüger, Sergiu Groppa
BACKGROUND: Lesional epilepsy is an important long-term sequela of stroke. Data on health-related quality of life (HrQoL) in patients with poststroke epilepsy are limited. We investigated HrQoL in patients with epilepsy after ischemic stroke and identified independent HrQoL-determinants. METHODS AND PATIENTS: All patients with acute ischemic stroke, who were permanent residents in the district Marburg-Biedenkopf (Hessia, Germany, reference population 240,000 inhabitants) were recruited within 12months in the population-based Marburg Stroke Register (MARSTREG)...
February 8, 2018: Epilepsy & Behavior: E&B
Christoph Vogelbacher, Thomas W D Möbius, Jens Sommer, Verena Schuster, Udo Dannlowski, Tilo Kircher, Astrid Dempfle, Andreas Jansen, Miriam H A Bopp
Large, longitudinal, multi-center MR neuroimaging studies require comprehensive quality assurance (QA) protocols for assessing the general quality of the compiled data, indicating potential malfunctions in the scanning equipment, and evaluating inter-site differences that need to be accounted for in subsequent analyses. We describe the implementation of a QA protocol for functional magnet resonance imaging (fMRI) data based on the regular measurement of an MRI phantom and an extensive variety of currently published QA statistics...
January 31, 2018: NeuroImage
Robert W Cross, Chad E Mire, Heinz Feldmann, Thomas W Geisbert
The filoviruses - Ebola virus and Marburg virus - cause lethal haemorrhagic fever in humans and non-human primates (NHPs). Filoviruses present a global health threat both as naturally acquired diseases and as potential agents of bioterrorism. In the recent 2013-2016 outbreak of Ebola virus, the most promising therapies for post-exposure use with demonstrated efficacy in the gold-standard NHP models of filovirus disease were unable to show statistically significant protection in patients infected with Ebola virus...
January 29, 2018: Nature Reviews. Drug Discovery
Wenjun Zhu, Zirui Zhang, Shihua He, Gary Wong, Logan Banadyga, Xiangguo Qiu
Filoviruses, such as Marburg and Ebola viruses, cause severe disease in humans with high case fatality rates and are therefore considered biological threat agents. To date, no licensed vaccine or therapeutic exists for their treatment. T-705 (favipiravir) is a pyrazinecarboxamide derivative that has shown broad antiviral activity against a number of viruses and is clinically licenced in Japan to treat influenza. Here we report the efficacy of T-705 against Marburg virus infection in vitro and in vivo. Notably, oral administration of T-705 beginning one or two days post-infection and continuing for eight days resulted in complete survival of mice that had been intraperitoneally infected with mouse-adapted Marburg virus (variant Angola)...
January 21, 2018: Antiviral Research
Zhihui Xie, Wei-Sheng Chen, Yuzhi Yin, Eunice C Chan, Kaoru Terai, Lauren M Long, Timothy G Myers, Arkadiusz Z Dudek, Kirk M Druey
BACKGROUND: Systemic Capillary Leak Syndrome (SCLS) is an extremely rare and life-threatening vascular disorder of unknown etiology. SCLS is characterized by abrupt and transient episodes of hypotensive shock and edema due to plasma leakage into peripheral tissues. The disorder has garnered attention recently because its initial presentation resembles more common vascular disorders including systemic anaphylaxis, sepsis, and acute infections with the Ebola/Marburg family of filoviruses...
January 23, 2018: Journal of Leukocyte Biology
Baptiste Martin, Olivier Reynard, Viktor Volchkov, Etienne Decroly
There are no approved medications for the treatment of Marburg or Ebola virus infection. In two previous articles (Martin et al., 2016, Martin et al., 2017), we reviewed surface glycoprotein and replication proteins structure/function relationship to decipher the molecular mechanisms of filovirus life cycle and identify antiviral strategies. In the present article, we recapitulate knowledge about the viral proteins involved in filovirus assembly and budding. First we describe the structural data available for viral proteins associated with virus assembly and virion egress and then, we integrate the structural features of these proteins in the functional context of the viral replication cycle...
January 2, 2018: Antiviral Research
Kendra J Alfson, Laura E Avena, Jenny Delgado, Michael W Beadles, Jean L Patterson, Ricardo Carrion, Anthony Griffiths
Marburg virus (MARV) causes disease with high case fatality rates, and there are no approved vaccines or therapies. Licensing of MARV countermeasures will likely require approval via the FDA's Animal Efficacy Rule, which requires well-characterized animal models that recapitulate human disease. This includes selection of the virus used for exposure and ensuring that it retains the properties of the original isolate. The consequences of amplification of MARV for challenge studies are unknown. Here, we serially passaged and characterized MARV through 13 passes from the original isolate...
January 2018: MSphere
Sandra L Bixler, Thomas M Bocan, Jay Wells, Kelly Wetzel, Sean Van Tongeren, Lian Dong, Nicole Lackemeyer, Ginger Donnelly, Lisa Cazares, Jonathan Nuss, Veronica Soloveva, Keith Koistinen, Lisa Welch, Carol Epstein, Li-Fang Liang, Dennis Giesing, Robert Lenk, Sina Bavari, Travis K Warren
Favipiravir is a broad-spectrum antiviral agent that has demonstrated efficacy against Ebola virus (EBOV) in rodents. However, there are no published reports of favipiravir efficacy for filovirus infection of nonhuman primates (NHPs). Here we evaluated the pharmacokinetic profile of favipiravir in NHPs, as well as in vivo efficacy against two filoviruses, EBOV and Marburg virus (MARV). While no survival benefit was observed in two studies employing once- or twice-daily oral dosing of favipiravir during EBOV infection of NHPs, an antiviral effect was observed in terms of extended time-to-death and reduced levels of viral RNA...
December 28, 2017: Antiviral Research
Sandra L Bixler, Thomas M Bocan, Jay Wells, Kelly Wetzel, Sean Van Tongeren, Nicole Lackemeyer, Ginger Donnelly, Lisa Cazares, Veronica Soloveva, Lisa Welch, Carol Epstein, Li-Fang Liang, Dennis Giesing, Robert Lenk, Sina Bavari, Travis K Warren
During the 2013-2016 Ebola virus (EBOV) outbreak in West Africa, our team at USAMRIID evaluated the antiviral activity of a number of compounds, including favipiravir (T-705), in vitro and in mouse and nonhuman primate (NHP) models of Ebola virus disease. In this short communication, we present our findings for favipiravir in cell culture and in mice, while an accompanying paper presents the results of NHP studies. We confirmed previous reports that favipiravir has anti-EBOV activity in mice. Additionally, we found that the active form of favipiravir is generated in mice in tissues relevant for the pathogenesis of EBOV infection...
December 28, 2017: Antiviral Research
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