A proinflammatory role for Fas in joints of mice with collagen-induced arthritis

Collagen-induced arthritis (CIA) is a chronic inflammatory disease bearing all the hallmarks of rheumatoid arthritis, e.g. polyarthritis, synovitis, and subsequent cartilage/bone erosions. One feature of the disease contributing to joint damage is synovial hyperplasia. The factors responsible for the hyperplasia are unknown; however, an imbalance between rates of cell proliferation and cell death (apoptosis) has been suggested. To evaluate the role of a major pathway of cell death – Fas (CD95)/FasL – in the pathogenesis of CIA, DBA/1J mice with a mutation of the Fas gene (lpr) were generated. The susceptibility of the mutant DBA-lpr/lpr mice to arthritis induced by collagen type II was evaluated. Contrary to expectations, the DBA-lpr/lpr mice developed significantly milder disease than the control littermates. The incidence of disease was also significantly lower in the lpr/lpr mice than in the controls (40% versus 81%; P < 0.05). However DBA-lpr/lpr mice mounted a robust immune response to collagen, and the expression of local proinflammatory cytokines such as, e.g., tumor necrosis factor α (TNF-α) and IL-6 were increased at the onset of disease. Since the contribution of synovial fibroblasts to inflammation and joint destruction is crucial, the potential activating effect of Fas on mouse fibroblast cell line NIH3T3 was investigated. On treatment with anti-Fas in vitro, the cell death of NIH3T3 fibroblasts was reduced and the expression of proinflammatory cytokines TNF-α and IL-6 was increased. These findings suggest that impairment of immune tolerance by increased T-cell reactivity does not lead to enhanced susceptibility to CIA and point to a role of Fas in joint destruction

Reliability of NI-RADS criteria in the interpretation of contrast-enhanced magnetic resonance imaging considering the potential role of diffusion-weighted imaging

Objectives: To assess inter- and intrareader agreement of the Neck Imaging Reporting and Data System (NI-RADS) used in contrast-enhanced magnetic resonance imaging (MRI) including analysis of diffusion-weighted imaging (DWI), which is currently not part of the NI-RADS criteria. Methods: This retrospective study included anonymized surveillance contrast-enhanced MRI datasets of 104 patients treated for different head and neck cancers. Three radiologists experienced in head and neck imaging reported findings for the primary site and the neck using NI-RADS criteria in a first step and evaluated DWI sequences for the primary site in a second step. Thirty randomly selected imaging datasets were again presented to the readers. Kappa statistics and observed agreement (A(o)) were calculated. Results: Interreader agreement across all MRI datasets was moderate (kappa(Fleiss) = 0.53) for NI-RADS categories assigned to the primary site, substantial for NI-RADS categories of the neck (kappa(Fleiss) = 0.67), and almost perfect for DWI of the primary site (kappa(Fleiss) = 0.83). Interreader agreement for the primary site was particularly low in cases of cancer recurrence (kappa(Fleiss) = 0.35) and when categories 2a, 2b, and 3 were combined (kappa(Fleiss) = 0.30). Intrareader agreement was considerably lower for NI-RADS categories of the primary site (range A(o) = 53.3-70.0%) than for NI-RADS categories of the neck (range A(o) = 83.3-90.0%) and DWI of the primary site (range A(o) = 93.3-100.0%). Conclusion: Interreader agreement of NI-RADS for reporting contrast-enhanced MRI findings is acceptable for the neck but limited for the primary site. Here, DWI has the potential to serve as a reliable additional criterion

Perforin deficiency attenuates collagen-induced arthritis

Collagen-induced arthritis (CIA), an approved animal model for rheumatoid arthritis, is thought to be a T cell-dependent disease. There is evidence that CD8(+ )T cells are a major subset controlling the pathogenesis of CIA. They probably contribute to certain features of disease, namely tissue destruction and synovial hyperplasia. In this study we examined the role of perforin (pfp), a key molecule of the cytotoxic death pathway that is expressed mainly in CD8(+ )T cells, for the pathogenesis of CIA. We generated DBA/1J mice suffering from mutations of the pfp molecule, DBA/1J-pfp(-/-), and studied their susceptibility to arthritis. As a result, pfp-deficient mice showed a reduced incidence (DBA/1J-pfp(+/+), 64%; DBA/1J-pfp(-/-), 54%), a slightly delayed onset (onset of disease: DBA/1J-pfp(+/+), 53 ± 3.6; DBA/1J-pfp(-/-), 59 ± 4.9 (mean ± SEM), and milder form of the disease (maximum disease score: DBA/1J-pfp(+/+), 7.3 ± 1.1; DBA/1J-pfp(-/-), 3.4 ± 1.4 (mean ± SEM); P < 0.05). Concomitantly, peripheral T cell proliferation in response to the specific antigen bovine collagen II was increased in pfp(-/- )mice compared with pfp(+/+ )mice, arguing for an impaired killing of autoreactive T cells caused by pfp deficiency. Thus, pfp-mediated cytotoxicity is involved in the initiation of tissue damage in arthritis, but pfp-independent cytotoxic death pathways might also contribute to CIA

Adjuvant Radiotherapy in Patients with Squamous Cell Carcinoma of the Oral Cavity or Oropharynx and Solitary Ipsilateral Lymph Node Metastasis (pN1) : A Prospective Multicentric Cohort Study

(1) Background: Evaluation of impact of adjuvant radiation therapy (RT) in patients with oral squamous cell carcinoma of the oral cavity/oropharynx (OSCC) of up to 4 cm (pT1/pT2) and solitary ipsilateral lymph node metastasis (pN1). A non-irradiated group with clinical follow-up was chosen for control, and survival and quality of life (QL) were compared; (2) Methods: This prospective multicentric comprehensive cohort study included patients with resected OSCC (pT1/pT2, pN1, and cM0) who were allocated into adjuvant radiation therapy (RT) or observation. The primary endpoint was overall survival. Secondary endpoints were progression-free survival and QL after surgery; (3) Results: Out of 27 centers, 209 patients were enrolled with a median follow-up of 3.4 years. An amount of 137 patients were in the observation arm, and 72 received adjuvant irradiation. Overall survival did not differ between groups (hazard ratio (HR) 0.98 [0.55–1.73], p = 0.94). There were fewer neck metastases (HR 0.34 [0.15–0.77]; p = 0.01), as well as fewer local recurrences (HR 0.41 [0.19–0.89]; p = 0.02) under adjuvant RT. For QL, irradiated patients showed higher values for the symptom scale pain after 0.5, two, and three years (all p < 0.05). After six months and three years, irradiated patients reported higher symptom burdens (impaired swallowing, speech, as well as teeth-related problems (all p < 0.05)). Patients in the RT group had significantly more problems with mouth opening after six months, one, and two years (p < 0.05); (4) Conclusions: Adjuvant RT in patients with early SCC of the oral cavity and oropharynx does not seem to influence overall survival, but it positively affects progression-free survival. However, irradiated patients report a significantly decreased QL up to three years after therapy compared to the observation group

Qualitätsentwicklung an Ganztagsschulen

Durch die Verlagerung bzw. Stärkung von Entscheidungskompetenzen auf die bzw. der Ebene der Einzelschule wird es ermöglicht, Lösungs-/Gestaltungsansätze zu entwickeln, die auf die jeweiligen Bedürfnisse und Gegebenheiten vor Ort zugeschnitten werden können. Die kritische Auseinandersetzung mit den Erfahrungen anderer, die auf entsprechenden Fortbildungsveranstaltungen kommuniziert werden können, lässt Good-practice-Beispiele entstehen, aus denen sich Anregungen zur Realisierung eigener Vorhaben im Zuge der Ganztagsschulentwicklung ableiten lassen. Der dritte bayerische Ganztagsschulkongress "Qualitätsentwicklung an Ganztagsschulen" am 1. und 2. März 2012 in Forchheim bot den Teilnehmerinnen und Teilnehmern anhand diverser Vorträge, Workshops und Schulbesuchen die Möglichkeit zu Diskussion und Austausch. Der vorliegende Band dokumentiert die Veranstaltung

Evaluierung von Chancen und Herausforderungen des Einsatzes von Social Web Software in der Aus- und Weiterbildung

Zusammenfassung in englischer SpracheTitelübersetzung des Autors: An evaluation of advantages and challenges of the use of social web software in educationSocial Web Software eröffnet Lehrenden neue und vielfältige Möglichkeiten der Gestaltung von problemorientierten, interaktiven und situierten Lernumgebungen. Durch die Einbeziehung der (Teil-)Öffentlichkeit in den Lernprozess können interessante, anspruchsvolle und lebensnahe Problemstellungen generiert sowie von den Lernenden in authentischen Lernsituationen gemeinsam bearbeitet werden. Durch das Feedback der Öffentlichkeit ergeben sich multiple und divergierende Perspektiven auf den Lerngegenstand. Zur gemeinsamen Wissenskonstruktion und zur Koordination von Gruppenprozessen kommen kollaborative Anwendungen und Social Networking-Plattformen zum Einsatz. Die Gestaltung von offenen und partizipativen Lernumgebungen impliziert eine Reihe von Veränderungen für Lernende und Lehrende, zudem sind seitens der Institution und Politik entsprechende Rahmenbedingungen zu schaffen. Die Chancen und Herausforderungen der Integration von Social Web Software in formale Lehr-/Lernsettings werden in dieser Arbeit im Rahmen einer Diskussion verschiedener didaktischer Konzepte, praxisbezogener Fallbeispiele sowie aktueller Forschungsergebnisse beleuchtet. Des Weiteren wird ein Vergleich mit den traditionellen, multifunktionalen Lernmanagementsystemen (LMS) angestellt. Diese etablierten Lernplattformen werden in der Praxis überwiegend für geschlossene und instruktionale Lehr-/Lernsettings herangezogen. Ein in den letzten Jahren viel diskutiertes Konzept für individuelles, selbstgesteuertes, eigenverantwortliches und gleichzeitig vernetztes, offenes, gemeinsames, fortlaufendes Online-Lernen stellen die Massive Open Online Courses (MOOCs) dar. Für eine fundierte Reflexion des MOOC-Phänomens ist zwischen den konnektivistisch orientierten, seminarähnlichen cMOOCs und den instruktional konzipierten, vorlesungsähnlichen xMOOCs zu differenzieren. Die kreativ-kollaborativen cMOOCs fokussieren die Vernetzung von Lernenden und Informationsquellen sowie das Generieren von neuem Wissen und koexistierenden Standpunkten durch einen regen Diskurs unter den Teilnehmenden. Im Gegensatz dazu verfolgen die xMOOCs durch strukturierte, videobasierte Lerninhalte und anschließende Aufgaben mit automatisiertem Feedback die Vermittlung von Wissen für eine große Anzahl an Personen. Basierend auf einer Bestandsaufnahme sowie einer Betrachtung der Potenziale und Schwächen von MOOCs wird in dieser Arbeit der mit diesen frei zugänglichen und kostenlosen Bildungsangeboten einhergehende Wandel der Lehr-/Lernkultur diskutiert.Social web software offers teachers and lecturers new and diverse possibilities of designing problem-oriented, interactive and situated learning environments. By involving the general public or a segment thereof in the learning process, interesting, challenging and true-to-life problems can be created and jointly dealt with by students in authentic learning situations. Feedback from the community results in multiple and diverging views on the subject of study. Online collaboration tools and social networking platforms are used for the cooperative creation of knowledge and for coordinating group processes. Establishing open and participatory learning environments implicates a number of changes for learners and teachers. In addition, the education system and politics need to create the necessary framework conditions. This paper discusses the opportunities and challenges of integrating social web software into formal teaching and learning settings by examining several didactic concepts, practice-oriented case studies and current research results. Furthermore, a comparison is drawn between these new learning environments and the traditional, multifunctional and widespread Learning Management Systems (LMS) which, in practice, are mainly used for closed and instructional teaching and learning settings. Massive Open Online Courses (MOOCs), which have been much discussed in the last few years, represent a model of individual, self-directed, self-reliant as well as networked, open, collaborative, and continuous online learning. In order to provide a well-funded analysis of the MOOC phenomenon, it is necessary to distinguish between cMOOCs (connectivist MOOCs), which are based on the concept of networked learning, and instructor-centric xMOOCs, which resemble traditional college courses. The creative-collaborative cMOOCs focus on connecting people and information, as well as on generating new knowledge and coexisting points of view through dialogue and active interaction among learners. Institutionally focused xMOOCs, on the other hand, are designed to deliver knowledge to larger audiences via pre-recorded short lecture videos combined with quizzes for self-assessment. MOOCs are free of charge and open to anyone. This paper examines the advantages and challenges of MOOCs in detail and discusses these online courses' impact on education.12