Cunt touch this: a conversation on intimate design and embarrassment

This position paper presents a conversation between players and the designers of the unique mobile game experience Cunt Touch This. Revisiting their personal experiences with playing the game, the player-authors read the game as a system that takes advantage of social embarrassment as a key element from which the pleasure of the game is derived. Contrasting this view, the designer-authors comment on the original intention, production context and purpose of Cunt Touch This. The goal of this confrontation is to explore embarrassment as a feeling oscillating between the emotional and the political dimensions of play. The unusual discussion format of the paper allows us to invite potentially challenging questions: When, where and why does embarrassment come about? What function does it have in play? Is it just part of the fun, or ideologically charged? Drawing together our differing perspectives as players and designers we contribute a candid reflection on the wider issues of embarrassment as it relates to design

Anthropologie als Antwort auf das konstatierte 'Theorie-Defizit' (in) der Medienpädagogik..?

In der vorliegenden Diplomarbeit wird aufmerksam zu machen gesucht auf die in medienpädagogischen Diskursen statthabende Revitalisierung einer problematisierungswürdigen Relationierung von Anthropologie und Pädagogik, gemäß derer Anthropologie das Fundament von Medienpädagogik bilde und sich diese von jener her begründen bzw. als Wissenschaft legitimieren lasse. Neben dem Aufweis solcher Argumentationsfiguren in medienpädagogischen Schriften zur Konstitution der – dort jeweils als theoretisch ungenügend fundiert zu denken gegebenen – (Teil-)Disziplin, zeigt die Arbeit (an und mit Texten) ferner auf, dass eine solche schon an sich problematische Relationierung ebenso problematische Annahmen zu Anthropologie und über den Menschen (als einem 'starken Subjekt') gleichsam birgt. Von einem kritischen Impetus getragen konfrontiert die vorliegende Arbeit die aufgewiesene Relationierung und insb. die dabei an- und mitgeführten Anthropologie- und Subjektfassungen mit exemplarischen (post-)anthropologischen und subjektkritischen Einsätzen in der Pädagogik. Michael Wimmers Auseinandersetzung mit traditioneller Anthropologie und Käte Meyer-Drawes Auseinandersetzung mit neuzeitlich-moderner Subjektivität werden auf die darin jeweils vorstellig gemachten Kennzeichnungen und Problematiken solcher Anthropologie- und Subjektfassungen hin gelesen. Entlang der so erschlossenen Kennzeichnungen lassen sich die in den aufgesuchten medienpädagogischen Texten vorfindlichen Annahmen zu Anthropologie und über den Menschen als von solchen Anthropologievarianten und Subjektfassungen tendenziell geprägte ansprechen. Insofern besagte Annahmen besagten Fassungen entsprechen, sind sie im Anschluss an die beiden zentralen Referenzautor_innen als problematische zu markieren; deren vorgetragene Kritik an traditioneller Anthropologie und neuzeitlich-moderner Subjektivität kann so geltend gemacht werden für die in medienpädagogischen Texten vorgebrachten Annahmen. Ihrem Selbstverständnis entsprechend wird in der vorliegenden Arbeit der Blick darüber hinaus auf die von Wimmer und Meyer-Drawe vorgelegten Neu-/Andersfassungen von Anthropologie bzw. Subjektivität gerichtet; so wird ein Weg aufzuzeigen versucht, anders über zentrale medienpädagogische Fragen nachzudenken

The evolution of human basophil biology from neglect towards understanding of their immune functions

Being discovered long ago basophils have been neglected for more than a century. During the past decade evidence emerged that basophils share features of innate and adaptive immunity. Nowadays, basophils are best known for their striking effector role in the allergic reaction. They hence have been used for establishing new diagnostic tests and therapeutic approaches and for characterizing natural and recombinant allergens as well as hypoallergens, which display lower or diminished IgE-binding activity. However, it was a long way from discovery in 1879 until identification of their function in hypersensitivity reactions, including adverse drug reactions. Starting with a historical background, this review highlights the modern view on basophil biology.(VLID)213835

Basophil Activation Test for Investigation of IgE-Mediated Mechanisms in Drug Hypersensitivity

Hypersensitivity reactions against non-steroidal anti-inflammatory drugs (NSAIDs) like propyphenazone (PP) and diclofenac (DF) can manifest as Type I-like allergic reactions 1. In clinical practice, diagnosis of drug hypersensitivity is mainly performed by patient history, as skin testing is not reliable and oral provocation testing bears life-threatening risks for the patient 2. Hence, evidence for an underlying IgE-mediated pathomechanism is hard to obtain

Dystonia Linked to EIF4A2 Haploinsufficiency: A Disorder of Protein Translation Dysfunction

Background: Protein synthesis is a tightly controlled process, involving a host of translation-initiation factors and microRNA-associated repressors. Variants in the translational regulator EIF2AK2 were first linked to neurodevelopmental-delay phenotypes, followed by their implication in dystonia. Recently, de novo variants in EIF4A2, encoding eukaryotic translation initiation factor 4A isoform 2 (eIF4A2), have been described in pediatric cases with developmental delay and intellectual disability. Objective: We sought to characterize the role of EIF4A2 variants in dystonic conditions. Methods: We undertook an unbiased search for likely deleterious variants in mutation-constrained genes among 1100 families studied with dystonia. Independent cohorts were screened for EIF4A2 variants. Western blotting and immunocytochemical studies were performed in patient-derived fibroblasts. Results: We report the discovery of a novel heterozygous EIF4A2 frameshift deletion (c.896_897del) in seven patients from two unrelated families. The disease was characterized by adolescence- to adulthood-onset dystonia with tremor. In patient-derived fibroblasts, eIF4A2 production amounted to only 50% of the normal quantity. Reduction of eIF4A2 was associated with abnormally increased levels of IMP1, a target of Ccr4-Not, the complex that interacts with eIF4A2 to mediate microRNA-dependent translational repression. By complementing the analyses with fibroblasts bearing EIF4A2 biallelic mutations, we established a correlation between IMP1 expression alterations and eIF4A2 functional dosage. Moreover, eIF4A2 and Ccr4-Not displayed significantly diminished colocalization in dystonia patient cells. Review of international databases identified EIF4A2 deletion variants (c.470_472del, c.1144_1145del) in another two dystonia-affected pedigrees. Conclusions: Our findings demonstrate that EIF4A2 haploinsufficiency underlies a previously unrecognized dominant dystonia-tremor syndrome. The data imply that translational deregulation is more broadly linked to both early neurodevelopmental phenotypes and later-onset dystonic conditions. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Lymphocyte Subsets Show Different Response Patterns to In Vivo Bound Natalizumab—A Flow Cytometric Study on Patients with Multiple Sclerosis

Natalizumab is an effective monoclonal antibody therapy for the treatment of relapsing- remitting multiple sclerosis (RRMS) and interferes with immune cell migration into the central nervous system by blocking the α4 subunit of very-late activation antigen-4 (VLA-4). Although well tolerated and very effective, some patients still suffer from relapses in spite of natalizumab therapy or from unwanted side effects like progressive multifocal leukoencephalopathy (PML). In search of a routine-qualified biomarker on the effectiveness of natalizumab therapy we applied flow cytometry and analyzed natalizumab binding to α4 and α4 integrin surface levels on T-cells, B-cells, natural killer (NK) cells, and NKT cells from 26 RRMS patients under up to 72 weeks of therapy. Four-weekly infusions of natalizumab resulted in a significant and sustained increase of lymphocyte-bound natalizumab (p<0.001) which was paralleled by a significant decrease in detectability of the α4 integrin subunit on all lymphocyte subsets (p<0.001). We observed pronounced natalizumab accumulations on T and B cells at single measurements in all patients who reported clinical disease activity (n = 4). The natalizumab binding capacity of in vitro saturated lymphocytes collected during therapy was strongly diminished compared to treatment-naive cells indicating a therapy-induced reduction of α4. Summing up, this pilot study shows that flow cytometry is a useful method to monitor natalizumab binding to lymphocytes from RRMS patients under therapy. Investigating natalizumab binding provides an opportunity to evaluate the molecular level of effectiveness of natalizumab therapy in individual patients. In combination with natalizumab saturation experiments, it possibly even provides a means of studying the feasability of patient-tailored infusion intervals. A routine-qualified biomarker on the basis of individual natalizumab saturation on lymphocyte subsets might be an effective tool to improve treatment safety

Diclofenac Hypersensitivity: Antibody Responses to the Parent Drug and Relevant Metabolites

Background: Hypersensitivity reactions against nonsteroidal antiinflammatory drugs (NSAIDs) like diclofenac (DF) can manifest as Type I-like allergic reactions including systemic anaphylaxis. However, except for isolated case studies experimental evidence for an IgE-mediated pathomechanism of DF hypersensitivity is lacking. In this study we aimed to investigate the possible involvement of drug-and/or metabolite-specific antibodies in selective DF hypersensitivity. Methodology/Principal Findings: DF, an organochemically synthesized linkage variant, and five major Phase I metabolites were covalently coupled to carrier proteins. Drug conjugates were analyzed for coupling degree and capacity to crosslink receptor-bound IgE antibodies from drug-sensitized mice. With these conjugates, the presence of hapten-specific IgE antibodies was investigated in patients' samples by ELISA, mediator release assay, and basophil activation test. Production of sulfidoleukotrienes by drug conjugates was determined in PBMCs from DF-hypersensitive patients. All conjugates were shown to carry more than two haptens per carrier molecule. Immunization of mice with drug conjugates induced drug-specific IgE antibodies capable of triggering mediator release. Therefore, the conjugates are suitable tools for detection of drug-specific antibodies and for determination of their anaphylactic activity. Fifty-nine patients were enrolled and categorized as hypersensitive either selectively to DF or to multiple NSAIDs. In none of the patients' samples evidence for drug/metabolite-specific IgE in serum or bound to allergic effector cells was found. In contrast, a small group of patients (8/59, 14%) displayed drug/metabolite-specific IgG. Conclusions/Significance: We found no evidence for an IgE-mediated effector mechanism based on haptenation of protein carriers in DF-hypersensitive patients. Furthermore, a potential involvement of the most relevant metabolites in DF hypersensitivity reactions could be excluded

Role and Relevance of Cerebrospinal Fluid Cells in Diagnostics and Research: State-of-the-Art and Underutilized Opportunities

Cerebrospinal fluid (CSF) has recently experienced a revival in diagnostics and research. However, little progress has been made regarding CSF cell analysis. For almost a century, CSF cell count and cytomorphological examination have been central diagnostic parameters, with CSF pleocytosis as a hallmark finding of neuroinflammation and cytology offering valuable clues regarding infectious, autoimmune, and malignant aetiologies. A great deal of information, however, remains unattended as modern immune phenotyping technologies have not yet been broadly incorporated into routine CSF analysis. This is a serious deficit considering the central role of CSF cells as effectors in central nervous system (CNS) immune defence and autoimmune CNS processes, and the diagnostic challenges posed by clinically overlapping infectious and immune-mediated CNS diseases. Here, we summarize historical, specimen-intrinsic, methodological, and technical issues determining the state-of-the-art diagnostics of CSF cells and outline future perspectives for this underutilized window into meningeal and CNS immunity