Mephistopheles\u27 Atopy, Allotry, Lottery. On textual proliferations in Goethe\u27s Faust I and II

Combining a careful reading of selected passages from Goethe’s Faust I and II and of marginal but nevertheless revealing lines on maybe the actual protagonist of the “Tragödie”, Mephistopheles, this paper aims to present aspects of what one could call Goethe’s vision of a modern devil. Taking departure from etymological considerations on the root of “diabolus”, i.e. diabállein, meaning to cast apart, to scatter, but also to accuse, as well as from different beliefs of German “Aberglaube” (superstition), it will become clear that one if not the major feature of Goethe’s Mephistopheles-figure is movement, not just in the spatial, but also in the temporal sense: Mephistopheles enacts different sediments of the devils cultural history and even travels to the mythical time of antiquity where something like a devil did not exist (atopia). Other than that, Mephistopheles always appears as an-other (allotria), no concept or principle seems to capture him, he does not appear to coincide with himself. Rather he incessantly multiplies “himself”, as his names are “legion”, constantly casting doubt on his plans, his identity, his site, not least as appearance itself (“Schein”), when he generates paper money (“Geldscheine”) and thus creates new means of apparent or rather virtual movement for the Kaiser in Faust II – cash flow

Reproducibility of the peritoneal regression grading score for assessment of response to therapy in peritoneal metastasis.

The four-tiered peritoneal regression grading score (PRGS) assesses the response to chemotherapy in peritoneal metastasis (PM). The PRGS is used, for example, to assess the response to pressurised intraperitoneal aerosol chemotherapy (PIPAC). However, the reproducibility of the PRGS is currently unknown. We aimed to evaluate the inter- and intraobserver variability of the PRGS. Thirty-three patients who underwent at least three PIPAC treatments as part of the PIPAC-OPC1 or PIPAC-OPC2 clinical trials at Odense University Hospital, Denmark, were included. Prior to each therapy cycle, peritoneal quadrant biopsies were obtained and three haematoxylin and eosin (H&E)-stained step sections were scanned and uploaded to a pseudonymised web library. For determining interobserver variability, eight pathologists assessed the PRGS for each quadrant biopsy, and Krippendorff's alpha and intraclass correlation coefficients (ICCs) were calculated. For determining intraobserver variability, three pathologists repeated their own assessments and Cohen's kappa and ICCs were calculated. A total of 331 peritoneal biopsies were analysed. Interobserver variability for PRGS of each biopsy and for the mean and maximum PRGS per biopsy set was moderate to good/substantial. The intraobserver variability for PRGS of each biopsy and for the mean and maximum PRGS per biopsy set was good to excellent/almost perfect. Our data support the PRGS as a reproducible and useful tool to assess response to intraperitoneal chemotherapy in PM. Future studies should evaluate the prognostic and predictive role of the PRGS

Role of immunohistochemistry for interobserver agreement of Peritoneal Regression Grading Score in peritoneal metastasis.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC)-directed therapy is a new treatment option for peritoneal metastasis (PM). The 4-tiered Peritoneal Regression Grading Score (PRGS) has been proposed for assessment of histological treatment response. We aimed to evaluate the effect of immunohistochemistry (IHC) on interobserver agreement of the PRGS. Hematoxylin and eosin (H&E)-stained and IHC-stained slides (n = 662) from 331 peritoneal quadrant biopsies (QBs) taken prior to 99 PIPAC procedures performed on 33 patients were digitalized and uploaded to a web library. Eight raters (five consultants and three residents) assessed the PRGS, and Krippendorff's alpha coefficients (α) were calculated. Results (IHC-PRGS) were compared with data published in 2019, using H&E-stained slides only (H&E-PRGS). Overall, agreement for IHC-PRGS was substantial to almost perfect. Agreement (all raters) regarding single QBs after treatment was substantial for IHC-PRGS (α = 0.69, 95% confidence interval [CI] = 0.66-0.72) and moderate for H&E-PRGS (α = 0.60, 95% CI = 0.56-0.64). Agreement (all raters) regarding the mean PRGS per QB set after treatment was higher for IHC-PRGS (α = 0.78, 95% CI = 0.73-0.83) than for H&E-PRGS (α = 0.71, 95% CI = 0.64-0.78). Among residents, agreement was almost perfect for IHC-PRGS and substantial for H&E-PRGS. Agreement (all raters) regarding maximum PRGS per QB set after treatment was substantial for IHC-PRGS (α = 0.61, 95% CI = 0.54-0.68) and moderate for H&E-PRGS (α = 0.60, 95% CI = 0.53-0.66). Among residents, agreement was substantial for IHC-PRGS (α = 0.66, 95% CI = 0.57-0.75) and moderate for H&E-PRGS (α = 0.55, 95% CI = 0.45-0.64). Additional IHC seems to improve the interobserver agreement of PRGS, particularly between less experienced raters

High-pressure nebulization as application route for the peritoneal administration of siRNA complexes

Peritoneal carcinomatosis is a severe form of cancer in the abdomen, currently treated with cytoreductive surgery and intravenous chemotherapy. Recently, nebulization has been proposed as a less invasive strategy for the local delivery of chemotherapeutic drugs. Also, RNA interference has been considered as a potential therapeutic approach for treatment of cancer. In this study, Lipofectamine RNAiMAX/siRNA complexes and cyclodextrin/siRNA complexes are evaluated before and after nebulization. Nebulization of the siRNA complexes does not significantly lower transfection efficiency when compared to non-nebulized complexes. After incubation in ascites fluid, however, the cyclodextrin/siRNA complexes show a drastic decrease in transfection efficiency. For the Lipofectamine RNAiMAX/siRNA complexes, this decrease is less pronounced. It is concluded that nebulization is an interesting technique to distribute siRNA complexes into the peritoneal cavity, providing the complexes are stable in ascites fluid which might be present in the peritoneal cavity

Antenatally diagnosed renal tumor: Questions

Background!#!Approximately 20% of antibody-mediated rejection (ABMR) episodes in the absence of donor-specific antibodies against human leucocyte antigens (HLA-DSA) in pediatric and adult kidney transplant recipients are associated with, and presumably caused by, antibodies against the angiotensin type 1 receptor (AT!##!Case!#!We report on a male patient with kidney failure in infancy due to obstructive uropathy who had lost his first kidney transplant due to AT!##!Conclusion!#!This case highlights the difficulty of persistently decreasing elevated A