Highly sensitive pyrogen detection on medical devices by the monocyte activation test

Pyrogens are components of microorganisms, like bacteria, viruses or fungi, which can induce a complex inflammatory response in the human body. Pyrogen contamination on medical devices prior operation is still critical and associated with severe complications for the patients. The aim of our study was to develop a reliable test, which allows detection of pyrogen contamination on the surface of medical devices. After in vitro pyrogen contamination of different medical devices and incubation in a rotation model, the human whole blood monocyte activation test (MAT), which is based on an IL-1β-specific ELISA, was employed. Our results show that when combining a modified MAT protocol and a dynamic incubation system, even smallest amounts of pyrogens can be directly detected on the surface of medical devices. Therefore, screening of medical devices prior clinical application using our novel assay, has the potential to significantly reduce complications associated with pyrogen-contaminated medical devices.     

Hans Scharoun’s ‘Dwelling Cells’ and the autonomy of architecture

This article traces a genealogy of three Berlin housing projects: Hans Scharoun’s housing estate Charlottenburg Nord (1956–1961); the Siedlung Siemensstadt (1929–1931), planned with Martin Wagner; the pre-modern reform block of Nonnendamm, designed by Johnson and Josef Feldhuber (1910–1912). Whilst for Scharoun the inversion of the figure of the perimeter block of Nonnendamm through the Zeilenbau organisation of Siemensstadt exemplifies modernism’s radical break from the past, it is the variegated form or Gestalt of Charlottenburg Nord that verifies the essential nature of a dwelling cell, or neighbourhood.

By contrast, this paper argues that Scharoun’s dwelling cell is the result of a continuous trajectory of typological reasoning. Each of the key spatial components of Nonnendamm—the figure of the block, the façade, the ground and the void—are taken up, hyper-articulated and re-configured, all in the service of the coherence and differentiation of a segment of the urban population. This trajectory exemplifies how modern architecture’s impetus for experimentation is taken into the service of and propels the broader reflection across disciplines regarding how to house and group the urban population.     

Understanding the combined influence of fine sediment and glyphosate herbicide on stream periphyton communities

Pesticides and deposited fine sediment have independently been associated with changes in relative abundance and species richness in aquatic ecosystems, but the interplay between these two stressors in agricultural streams is poorly understood. A 28-day experiment in outdoor stream mesocosms examined the effects of four levels each of fine sediment coverage (0, 25, 75, 100%) and glyphosate-based herbicide concentration (0, 50, 200, 370 μg/L) on periphyton communities (algae and bacteria) in a fully factorial, repeated-measures design. Our aims were to determine whether (i) increased levels of sediment and glyphosate had individual and/or additive effects, (ii) increased sediment reduced the toxicity of glyphosate (antagonistic multiple stressor interaction), or (iii) sediment-adsorbed glyphosate prolonged the effects of exposure (synergistic interaction). We also assigned all algal taxa to three ecological guilds (low-profile, high-profile and motile growth forms) and separately determined their responses to the treatments. As individual stressors, sediment addition affected all algal community-level metrics, whereas glyphosate addition only affected algal community evenness. Bacterial taxon richness was unaffected by either stressor. In combination, however, significant overall sediment by glyphosate interactions were detected, demonstrating synergistic (algal evenness, high-profile and motile guilds) or antagonistic effects (low-profile guild). Our experiment underscores the importance of considering both structural and functional indicators, including algal guild representation, when assessing the mechanisms by which periphyton communities respond to multiple stressors.     

Challenges of Using Expansion Microscopy for Super-resolved Imaging of Cellular Organelles

Expansion microscopy (ExM) has been successfully used to improve the spatial resolution when imaging tissues by optical microscopy. In ExM, proteins of a fixed sample are crosslinked to a swellable acrylamide gel, which expands when incubated in water. Therefore, ExM allows enlarged subcellular structures to be resolved that would otherwise be hidden to standard confocal microscopy. Herein, we aim to validate ExM for the study of peroxisomes, mitochondria, nuclei and the plasma membrane. Upon comparison of the expansion factors of these cellular compartments in HEK293 cells within the same gel, we found significant differences, of a factor of above 2, in expansion factors. For peroxisomes, the expansion factor differed even between peroxisomal membrane and matrix marker; this underlines the need for a thorough validation of expansion factors of this powerful technique. We further give an overview of possible quantification methods for the determination of expansion factors of intracellular organelles, and we highlight some potentials and challenges.     

Lynch Syndrome: Its Impact on Urothelial Carcinoma

Lynch syndrome, known as hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal-dominant familial cancer syndrome with an increased risk for urothelial cancer (UC). Mismatch repair (MMR) deficiency, due to pathogenic variants in MLH1, MSH2, MSH6, and PMS2, and microsatellite instability, are known for development of Lynch syndrome (LS) associated carcinogenesis. UC is the third most common cancer type in LS-associated tumors. The diversity of germline variants in the affected MMR genes and their following subsequent function loss might be responsible for the variation in cancer risk, suggesting an increased risk of developing UC in MSH2 mutation carriers. In this review, we will focus on LS-associated UC of the upper urinary tract (UUT) and bladder, their germline profiles, and outcomes compared to sporadic UC, the impact of genetic testing, as well as urological follow-up strategies in LS. In addition, we present a case of metastatic LS-associated UC of the UUT and bladder, achieving complete response during checkpoint inhibition since more than 2 years.