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Filoviruses infect a wide range of cell types with the exception of lymphocytes. The intracellular proteins cathepsin B and L, two-pore channel 1 and 2, and bona fide receptor Niemann–Pick Disease C1 (NPC1) are essential for the endosomal phase of cell entry. However, earlier steps of filoviral infection remain poorly characterized. Numerous plasma membrane proteins have been implicated in attachment but it is still unclear which ones are sufficient for productive entry. To define a minimal set of host factors required for filoviral glycoprotein-driven cell entry, we screened twelve cell lines and identified the nonlymphocytic cell line SH-SY5Y to be specifically resistant to filovirus infection. Heterokaryons of SH-SY5Y cells fused to susceptible cells were susceptible to filoviruses, indicating that SH-SY5Y cells do not express a restriction factor but lack an enabling factor critical for filovirus entry. However, all tested cell lines expressed functional intracellular factors. Global gene expression profiling of known cell surface entry factors and protein expression levels of analyzed attachment factors did not reveal any correlation between susceptibility and expression of a specific host factor. Using binding assays with recombinant filovirus glycoprotein, we identified cell attachment as the step impaired in filovirus entry in SH-SY5Y cells. Individual overexpression of attachment factors T-cell immunoglobulin and mucin domain 1 (TIM-1), Axl, Mer, or dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) rendered SH-SY5Y cells susceptible to filovirus glycoprotein-driven transduction. Our study reveals that a lack of attachment factors limits filovirus entry and provides direct experimental support for a model of filoviral cell attachment where host factor usage at the cell surface is highly promiscuous.
Background: Available data on the incidence and outcome of invasive fungal diseases (IFD) in children with hematological malignancies or after allogeneic hematopoietic stem cell transplantation (HSCT) are mostly based on monocenter, retrospective studies or on studies performed prior to the availability of newer triazoles or echinocandins.
Procedure: We prospectively collected clinical data on incidence, diagnostic procedures, management and outcome of IFD in children treated for hematological malignancies or undergoing HSCT in three major European pediatric cancer centers.
Results: A total of 304 children (median age 6.0 years) who underwent 360 therapies (211 chemotherapy treatments, 138 allogeneic HSCTs and/or 11 investigational chemotherapeutic treatments) were included in the analysis. Nineteen children developed proven/probable IFD, mostly due to Aspergillus (n = 10) and Candida spp. (n = 5), respectively. In patients receiving chemotherapy, 11 IFDs occurred, all during induction or re-induction therapy. None of these patients died due to IFD, whereas IFD was lethal in 3 of the 8 HSCT recipients with IFD. Significant differences among centers were observed with regard to the use of imaging diagnostics and the choice, initiation and duration of antifungal prophylaxis.
Conclusion: This prospective multicenter study provides information on the current incidence and outcome of IFD in the real life setting. Practice variation between the centers may help to ultimately improve antifungal management in children at highest risk for IFDs.
Rezensionen [2019]
(2019)
Verzeichnis
Einzelrezensionen
163 Babenhauserheide, Melanie: Harry Potter und die Widersprüche der Kulturindustrie. Eine ideologiekritische Analyse (DAVID N. SCHMIDT)
165 Ballis, Anja/Pecher, Claudia Maria/ Schuler, Rebecca (Hrsg.): Mehrsprachige Kinder- und Jugendliteratur. Überlegungen zur Systematik, Didaktik und Verbreitung (SVETLANA VISHEK)
167 Bannasch, Bettina/Matthes, Eva (Hrsg.): Kinder- und Jugendliteratur. Historische, erzähl- und medientheoretische, pädagogische und therapeutische Perspektiven (susanne blumesberger)
169 Batzke, Ina/ Erbacher, Eric C. /Heß, Linda M. / Lenhardt, Corinna (Hrsg.): Exploring the Fantastic. Genre, Ideology, and Popular Culture (THOMAS BITTERLICH)
170 Bertling, Maria: All-Age-Literatur. Die Entdeckung einer neuen Zielgruppe und ihrer Rezeptionsmodalitäten (NICOLA KÖNIG)
172 Blümer, Agnes: Mehrdeutigkeit übersetzen. Englische und französische Kinderliteraturklassiker der Nachkriegszeit in deutscher Übertrag (MARTINA SEIFERT)
174 Blumesberger, Susanne/Thunecke, Jörg (Hrsg.): Deutschsprachige Kinder- und Jugendliteratur während der Zwischenkriegszeit und im Exil. Schwerpunkt Österreich (KURT FRANZ)
176 Busch, Nathanael /Velten, Hans Rudolf (Hrsg.): Die Literatur des Mittelalters im Fantasyroman (SONJA LOIDL)
178 Cave, Roderick/Ayad, Sara (Hrsg.): Die Geschichte des Kinderbuches in 100 Büchern (ERNST SEIBERT)
180 Dettmar, Ute/Pecher, Claudia Maria/Schlesinger, Ron (Hrsg.): Märchen im Medienwechsel. Zur Geschichte und Gegenwart des Märchenfilms (MICHAEL STIERSTORFER)
182 Dommermuth, Clarissa: Wir sind dagegen – denn ihr seid dafür. Zur Tradition literarischer Jugendbewegungen im deutschsprachigen Raum (SUSANNE BLUMESBERGER)
184 Ellerbach, Benoît: L’Arabie contée aux Allemands. Fictions interculturelles chez Rafik Schami (ANNETTE KLIEWER)
185 Enklaar, Jattie/ Ester, Hans /Tax, Evelyne (Hrsg.): Studien über Kinder- und Jugendliteratur im europäischen Austausch von 1800 bis heute (IRIS SCHÄFER)
187 Ewers, Hans-Heino: Michael Ende neu entdecken. Was »Jim Knopf«,»Momo« und »Die unendliche Geschichte« Erwachsenen zu sagen haben (MARKUS JANKA)
189 Flegel, Monica/Parkes, Christopher (Hrsg.): Cruel Children in Popular Texts and Cultures (LENA HOFFMANN)
191 Garbe, Christine/Gürth, Christina et al. (Hrsg.): Attraktive Lesestoffe (nicht nur) für Jungen. Erzählmuster und Beispielanalysen zu populärer Kinder- und Jugendliteratur (THOMAS BITTERLICH)
193 Goga, Nina/Kümmerling-Meibauer, Bettina (Hrsg.): Maps and Mapping in Children’s Literature. Landscapes, Seascapes, and Cityscapes (Wolfgang Biesterfeld)
195 Hamer, Naomi /Nodelman, Perry / Reimer, Mavis (Hrsg.): More Words about Pictures. Current Research on Picturebooks and Visual/Verbal Texts for Young People (FARRIBA SCHULZ)
196 Hoffmann, Lena: Crossover. Mehrfachadressierung in Text, Markt und Diskurs (HEIDI LEXE)
198 Josting, Petra/Reuter, Frank/Roeder, Caroline/Wolters, Ute (Hrsg.): »Denn sie rauben sehr geschwind jedes böse Gassenkind.« ›Zigeuner‹-Bilder in Kinder- und Jugendmedien (KURT FRANZ)
200 Langemeyer, Peter /Knutsen, Karen Patrick (Hrsg.): Narratology Plus. Studies in Recent International Narratives for Children and
Young Adults / Narratologie Plus. Studien zur Erzählweise in aktueller internationaler Kinder- und Jugendliteratur (NADINE BIEKER)
202 Museumsinsel Lüttenheid (Hrsg.): Rudolf Dirks. Zwei Lausbuben und die Erfindung des modernen Comics (LUKAS SARVARI)
204 Oeste, Bettina/Preußer, Ulrike (Hrsg.): Neuvermessung deutschsprachiger Erinnerungsstrategien in der Kinder- und Jugendliteratur nach 1990 (annette kliewer)
206 Planka, Sabine (Hrsg.): Berlin. Bilder einer Metropole in erzählenden Medien für Kinder und Jugendliche (KATHARINA EGERER)
208 Press, Alexander: Die Bilder des Comics. Funktionsweisen aus kunst- und bildwissenschaftlicher Perspektive (RALF VOLLBRECHT)
209 Schenk, Klaus /Zeisberg, Ingold (Hrsg.): Fremde Räume. Interkulturalität und Semiotik des Phantastischen (ANNETTE KLIEWER)
211 Schweizerisches Institut für Kinder- und Jugendmedien SIKJM (Hrsg.): Atlas der Schweizer Kinderliteratur. Expeditionen und
Panoramen (SUSANNE RIEGLER)
Sammelrezensionen
213 Heinemann, Caroline: Produktionsräume im zeitgenössischen Kinder- und Jugendtheater. – Hentschel, Ingrid: Theater zwischen Ich und Welt. Beiträge zur Ästhetik des Kinder- und Jugendtheaters. Theorien – Praxis – Geschichte (PHILIPP SCHMERHEIM)
215 Janka, Marcus /Stierstorfer, Michael (Hrsg.): Verjüngte Antike. Griechisch-römische Mythologie in zeitgenössischen Kinder- und Jugendmedien. – Stierstorfer, Michael: Antike Mythologie in der Kinder- und Jugendliteratur der Gegenwart. Unsterbliche Götter- und Heldengeschichten? (KARINA BECKER)
218 Josting, Petra/Kruse, Iris (Hrsg.): Paul Maar. Bielefelder Poet in Residence 2015 | Paderborner Kinderliteraturtage 2016. – Wicke, Andreas /Roßbach, Nikola (Hrsg.): Paul Maar. Studien zum kinder- und jugendliterarischen Werk (SONJA MÜLLER-CARSTENS)
Objective: Biologics have an important role in the treatment of juvenile idiopathic arthritis (JIA). Long‐term safety data are limited. Direct comparison of different agents regarding occurrence of adverse events (AEs), especially of rare events, requires large quantities of patient years. In this analysis, long‐term safety with regard to AE of special interest (AESI) was compared between different biologics.
Methods: Patients with nonsystemic JIA were selected from the German BIKER registry. Safety assessments were based on AE reports. Number of AEs, serious AEs, and 25 predefined AESIs, including medically important infection, uveitis, inflammatory bowel disease, cytopenia, hepatic events, anaphylaxis, depression, pregnancy, malignancy, and death, were analyzed. Event rates and relative risks were calculated using AEs reported after first dose through 70 days after last dose.
Results: A total of 3873 patients entered the analysis with 7467 years of exposure to biologics. The most common AESIs were uveitis (n = 231) and medically important infections (n = 101). Cytopenia and elevation of transaminases were more frequent with tocilizumab (risk ratio [RR] 8.0, 95% confidence interval [CI] 4.2‐15, and RR 4.7, 95% CI 1.8‐12.2, respectively). Anaphylactic events were associated with intravenous route of administration. In patients ever exposed to biologics, eight malignancies were reported. Six pregnancies have been documented in patients with tumor necrosis factor inhibitors. No death occurred in this patient cohort during observation.
Conclusion: Surveillance of pharmacotherapy as provided by the BIKER registry is an import approach, especially for long‐term treatment of children. Overall, tolerance was acceptable. Differences between biologics were noted and should be considered in daily patient care.