A UV-sensitive syndrome patient with a specific CSA mutation reveals separable roles for CSA in response to UV and oxidative DNA damage

UV-sensitive syndrome (UVSS) is a recently-identified autosomal recessive disorder characterized by mild cutaneous symptoms and defective transcription-coupled repair (TC-NER), the subpathway of nucleotide excision repair (NER) that rapidly removes damage that can block progression of the transcription machinery in actively-transcribed regions of DNA. Cockayne syndrome (CS) is another genetic disorder with sun sensitivity and defective TC-NER, caused by mutations in the CSA or CSB genes. The clinical hallmarks of CS include neurological/developmental abnormalities and premature aging. UVSS is genetically heterogeneous, in that it appears in individuals with mutations in CSB or in a still-unidentified gene. We report the identification of a UVSS patient (UVSS1VI) with a novel mutation in the CSA gene (p.trp361cys) that confers hypersensitivity to UV light, but not to inducers of oxidative damage that are notably cytotoxic in cells from CS patients. The defect in UVSS1VI cells is corrected by expression of the WT CSA gene. Expression of the p.trp361cys-mutated CSA cDNA increases the resistance of cells from a CS-A patient to oxidative stress, but does not correct their UV hypersensitivity. These findings imply that some mutations in the CSA gene may interfere with the TC-NER-dependent removal of UV-induced damage without affecting its role in the oxidative stress response. The differential sensitivity toward oxidative stress might explain the difference between the range and severity of symptoms in CS and the mild manifestations in UVsS patients that are limited to skin photosensitivity without precocious aging or neurodegeneration

AngioJet rheolytic thrombectomy in patients presenting with high-risk pulmonary embolism and cardiogenic shock: a feasibility pilot study

Aims: Pulmonary embolism (PE) associated with haemodynamic instability has exceedingly high mortality. While intravenous thrombolysis is considered the therapy of choice, percutaneous mechanical thrombectomy may represent an alternative treatment. Methods and results: The impact of AngioJet® rheolytic thrombectomy (RT) in PE associated with cardiogenic shock was assessed in a single-centre prospective pilot study. Ten consecutive PE patients in cardiogenic shock were included in the study. Six patients had thrombolysis contraindications, eight were intubated before the RT procedure and six had experienced cardiac arrest prior to the RT procedure. The RT procedure was technically successful in all cases. The Miller index improved from 25 to 20 (p=0.002). The shock index decreased from 1.22 to 0.9 (p=0.129). Thrombolytic agents were administered during or after the procedure in four patients because of progressive clinical deterioration. Seven patients died in the first 24 hours: two from multi-organ failure, one from post-anoxic cerebral oedema, and four from progressive right heart failure. The three survivors had favourable outcomes at one year. Conclusions: This study suggests that the AngioJet® RT procedure may be safely performed in PE patients with cardiogenic shock. However, despite angiographic and haemodynamic improvements, the procedure does not appear to influence the dismal prognosis of these high-risk patients

Ein Virus testet den Wohlfahrtsstaat

This essay discusses some of the consequences of the widely observed resurgence of a strong interventionist state during the corona crisis. Its focus is on how health and welfare arrangements impact the elderly, the group primarily affected by COVID-19. Four related perspectives – viewing the crisis as a “natural experiment,” the relationship between experts and politics, biopolitical arguments, and age discrimination – are used to unpack the major inequalities, tensions and deficits in the social and sanitary policies of Western Europe and the US

Heterogeneous knowledge: Trends in German discourse analysis against an international background

This contribution maps the complex field of discourse analysis in Germany by situating its major currents and putting them in historical perspective. In a first step, it presents the major intellectual sources, such as (post-)structuralism, pragmatism/interactionism as well as hermeneutics, which have served as a backdrop for the establishment of discourse analysis as an interdisciplinary field since the 1980s. In a second step, it takes a closer look at the intellectual conjunctures in the social sciences such as Critical Theory and systems theory before turning to the discourse analytical tendencies that have emerged since the 1980s in the light of Foucault's reception in Germany. Finally, it discusses the features of heterogeneous knowledge discourses. As against top-down studies of political discourse in France and bottom-up investigations of everyday discourse in the US, many discourse analysts in Germany focus on knowledge production as a multi-leveled process involving texts and contexts. Therefore, discourse is seen as a heterogeneous object constructed in the interplay of language, praxis and knowledge