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Voigt, Gesche M. ; Thiele, Dominik ; Wetzke, Martin ; Weidemann, Jürgen ; Parpatt, Patricia‐Maria ; Welte, Tobias ; Seidenberg, Jürgen ; Vogelberg, Christian ; Köster, Holger ; Rohde, Gernot Gerhard Ulrich ; Härtel, Christoph ; Hansen, Gesine ; Kopp, Matthias
Although chest radiograph (CXR) is commonly used in diagnosing pediatric community acquired pneumonia (pCAP), limited data on interobserver agreement among radiologists exist. PedCAPNETZ is a prospective, observational, and multicenter study on pCAP. N = 233 CXR from patients with clinical diagnosis of pCAP were retrieved and n = 12 CXR without pathological findings were added. All CXR were interpreted by a radiologist at the site of recruitment and by two external, blinded pediatric radiologists. To evaluate interobserver agreement, the reporting of presence or absence of pCAP in CXR was analyzed, and prevalence and bias-adjusted kappa (PABAK) statistical testing was applied. Overall, n = 190 (82%) of CXR were confirmed as pCAP by two external pediatric radiologists. Compared with patients with pCAP negative CXR, patients with CXR-confirmed pCAP displayed higher C-reactive protein levels and a longer duration of symptoms before enrollment (p < .007). Further parameters, that is, age, respiratory rate, and oxygen saturation showed no significant difference. The interobserver agreement between the onsite radiologists and each of the two independent pediatric radiologists for the presence of pCAP was poor to fair (69%; PABAK = 0.39% and 76%; PABAK = 0.53, respectively). The concordance between the external radiologists was fair (81%; PABAK = 0.62). With regard to typical CXR findings for pCAP, chance corrected interrater agreement was highest for pleural effusions, infiltrates, and consolidations and lowest for interstitial patterns and peribronchial thickening. Our data show a poor interobserver agreement in the CXR-based diagnosis of pCAP and emphasized the need for harmonized interpretation standards.
Klionsky, Daniel ; Petroni, Giulia ; Amaravadi, Ravi K. ; Baehrecke, Eric H. ; Ballabio, Andrea ; Boya, Patricia ; Bravo-San Pedro, José Manuel ; Cadwell, Ken ; Cecconi, Francesco ; Choi, Augustine M. K. ; Choi, Mary E. ; Chu, Charleen T. ; Codogno, Patrice ; Colombo, Maria Isabel ; Cuervo, Ana Maria ; Deretic, Vojo ; Đikić, Ivan ; Elazar, Zvulun ; Eskelinen, Eeva-Liisa ; Fimia, Gian Maria ; Gewirtz, David A. ; Green, Douglas R. ; Hansen, Malene ; Jäättelä, Marja ; Johansen, Terje ; Juhász, Gábor ; Karantza, Vassiliki ; Kraft, Claudine ; Kroemer, Guido ; Ktistakis, Nicholas T. ; Kumar, Sharad ; López Otín, Carlos ; Macleod, Kay F. ; Madeo, Frank ; Martinez, Jennifer ; Meléndez, Alicia ; Mizushima, Noboru ; Münz, Christian ; Penninger, Josef Martin ; Perera, Rushika M. ; Piacentini, Mauro ; Reggiori, Fulvio ; Rubinsztein, David C. ; Ryan, Kevin M. ; Sadoshima, Junichi ; Santambrogio, Laura ; Scorrano, Luca ; Simon, Hans-Uwe ; Simon, Anna Katharina ; Simonsen, Anne ; Stolz, Alexandra ; Tavernarakis, Nektarios ; Tooze, Sharon A. ; Yoshimori, Tamotsu ; Yuan, Junying ; Yue, Zhenyu ; Zhong, Qing ; Galluzzi, Lorenzo ; Pietrocola, Federico
Autophagy is a core molecular pathway for the preservation of cellular and organismal homeostasis. Pharmacological and genetic interventions impairing autophagy responses promote or aggravate disease in a plethora of experimental models. Consistently, mutations in autophagy-related processes cause severe human pathologies. Here, we review and discuss preclinical data linking autophagy dysfunction to the pathogenesis of major human disorders including cancer as well as cardiovascular, neurodegenerative, metabolic, pulmonary, renal, infectious, musculoskeletal, and ocular disorders.
Der Indianer ist eine Figur, die mit James Fenimore Cooper (1789-1851) Eingang in deutsche Wohnzimmer erhalten hat und nicht erst mit Karl May (1842-1912) ein fester Bestandteil des deutschen kulturellen Gedächtnisses geworden ist. Den Phänomenen Cooper und May ist bereits weitreichende Aufmerksamkeit in unterschiedlichen Disziplinen zuteil geworden, allerdings werden dabei zum einen verschiedene Schriften anderer Autoren zur Thematik ausgeblendet und zum anderen wird die Frage nach der Funktion der Konstruktion des deutschen Indianers nur an der Oberfläche behandelt. Zumeist beschränken sich die Betrachtungen auf den Verweis auf Exotismus, Abenteuer und Sehnsucht nach dem Fremden, vereinzelt wird auf eine mögliche Zivilisationskritik eingegangen. Dabei geht die Funktionalisierung des deutschen Indianers darüber hinaus. Tatsächlich ist der Indianer auch ein Mittel zur Schaffung und Etablierung einer deutschen Identität in den lang währenden Umbruchzeiten des 19. Jahrhunderts. Bisher ist es versäumt worden, einen umfassenden Nachweis der These anhand zeitgenössischer Quellen zu leisten. Mit Hilfe der Historischen Stereotypenforschung lässt sich über die Analyse der Auto- und Heterostereotype dem genannten Desiderat entsprechen.
In diesem Aufsatz möchten wir Denk- und Deutungsmuster des mediengestützten Studiums und der mediengestützten Lehre herausarbeiten, welche die These einer qualitativ neuen Form der Bildung stützen2. Der Rahmen, in dem wir uns dabei bewegen, wird einerseits durch die Debatte um die Wissensgesellschaft und andererseits durch die Perspektive der kanadischen Medientheorie3 gekennzeichnet.
Unser Augenmerk gilt den Veränderungen in unserer Alltagskultur, den Deutungs- und Wahrnehmungsmustern und den entsprechenden Erwartungshorizonten, welche sich zunehmend unter den Bedingungen moderner Medientechnologien verändern. Besonders hervorheben wollen wir dabei den Zusammenhang von medientechnischen und kulturellen Modernisierungen. Fragen der Entwicklung und Nutzung neuer Medientechnologien wie dem Internet lassen sich so jenseits einer Sichtweise der Instrumentalisierung in den Blick nehmen. Wir werden uns bei den nachfolgenden Betrachtungen dazuhin auf das Feld der Hochschulen und die dort angesiedelten Fragen zur mediengestützten Lehre beschränken.
Wetzke, Martin ; Kopp, Matthias ; Seidenberg, Jürgen ; Vogelberg, Christian ; Ankermann, Tobias ; Happle, Christine ; Voigt, Gesche ; Köster, Holger ; Illig, Thomas ; Lex, Christiane ; Schuster, Antje ; Panning, Marcus ; Barten, Grit ; Rohde, Gernot Gerhard Ulrich ; Welte, Tobias ; Hansen, Gesine
Background: Pediatric community acquired pneumonia (pedCAP) is one of the leading causes for childhood morbidity accounting for up to 20% of pediatric hospital admissions in high income countries. In spite of its high morbidity, updated epidemiological and pathogen data after introduction of preventive vaccination and novel pathogen screening strategies are limited. Moreover, there is a need for validated recommendations on diagnostic and treatment regimens in pedCAP. Through collection of patient data and analysis of pathogen and host factors in a large sample of unselected pedCAP patients in Germany, we aim to address and substantially improve this situation.
Methods: pedCAPNETZ is an observational, multi-center study on pedCAP. Thus far, nine study centers in hospitals, outpatient clinics and practices have been initiated and more than 400 patients with radiologically confirmed pneumonia have been enrolled, aiming at a total of 1000 study participants. Employing an online data base, information on disease course, treatment as well as demographical and socioeconomical data is recorded. Patients are followed up until day 90 after enrollment; Comprehensive biosample collection and a central pedCAPNETZ biobank allow for in-depth analyses of pathogen and host factors. Standardized workflows to assure sample logistics and data management in more than fifteen future study centers have been established.
Discussion: Through comprehensive epidemiological, clinical and biological analyses, pedCAPNETZ fills an important gap in pediatric and infection research. To secure dissemination of the registry, we will raise clinical and scientific awareness at all levels. We aim at participating in decision making processes for guidelines and prevention strategies. Ultimately, we hope the results of the pedCAPNETZ registry will help to improve care and quality of life in pedCAP patients in the future.
Hansen, Anne-Louise Smidt ; Buchan, Gregory J. ; Rühl, Michael ; Mukai, Kojiro ; Salvatore, Sonia R. ; Ogawa, Emari ; Andersen, Sidsel ; Iversen, Marie B. ; Thielke, Anne L. ; Gunderstofte, Camilla ; Motwani, Mona ; Møller, Charlotte T. ; Jakobsen, Andreas S. ; Fitzgerald, Katherine A. ; Roos, Jessica ; Lin, Rongtuan ; Maier, Thorsten Jürgen ; Goldbach-Mansky, Raphaela ; Miner, Cathrine A. ; Qian, Wei ; Miner, Jonathan ; Rigby, Rachel ; Rehwinkel, Jan ; Jakobsen, Martin R. ; Arai, Hiroyuki ; Taguchi, Tomohiko ; Schopfer, Francisco J. ; Olagnier, David ; Holm, Christian K.
The adaptor molecule stimulator of IFN genes (STING) is central to production of type I IFNs in response to infection with DNA viruses and to presence of host DNA in the cytosol. Excessive release of type I IFNs through STING-dependent mechanisms has emerged as a central driver of several interferonopathies, including systemic lupus erythematosus (SLE), Aicardi–Goutières syndrome (AGS), and stimulator of IFN genes-associated vasculopathy with onset in infancy (SAVI). The involvement of STING in these diseases points to an unmet need for the development of agents that inhibit STING signaling. Here, we report that endogenously formed nitro-fatty acids can covalently modify STING by nitro-alkylation. These nitro-alkylations inhibit STING palmitoylation, STING signaling, and subsequently, the release of type I IFN in both human and murine cells. Furthermore, treatment with nitro-fatty acids was sufficient to inhibit production of type I IFN in fibroblasts derived from SAVI patients with a gain-of-function mutation in STING. In conclusion, we have identified nitro-fatty acids as endogenously formed inhibitors of STING signaling and propose for these lipids to be considered in the treatment of STING-dependent inflammatory diseases.