Patient Blood Management in der Geburtsvorbereitung,Geburtshilfe und postpartalen Phase

Die Anaesthesiologie - Die Implementierung eines Patient Blood Management (PBM) wird zunehmender Standard in der operativen Medizin. Seit einiger Zeit gilt das Interesse auch den vulnerablen...     

Heritable Genome Editing in a Global Context: National and International Policy Challenges

A central problem for the international governance of heritable germline gene editing is that there are important differences in attitudes and values as well as ethical and health care considerations around the world. These differences are reflected in a complicated and diverse regulatory landscape. Several publications have discussed whether reproductive uses would be legally permissible in individual countries and whether clinical applications could emerge in the context of regulatory gaps and gray areas. Systematic comparative studies that explore issues related to the governance of this technology from different national and international perspectives are needed to address the lack of knowledge in this area. In this research report, we contribute to filling this gap by presenting views of stakeholders in the United Kingdom on challenges to the governance of heritable genome editing. We present findings from a multistakeholder study conducted in the United Kingdom between October 2016 and January 2018 and funded by the Wellcome Trust. This research included interviews, literature analysis, and a workshop. We involved leading U.K. scientists, in vitro fertilization clinicians, and representatives from regulatory bodies, patient organizations, and other civil societal organizations, as well as fertility companies. Part one of this article explores stakeholder perceptions of possible global developments in heritable genome editing and associated risks and governance challenges. Part two presents a range of policy options that were generated during the workshop in relation to the challenges discussed in part one.     

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European Spine Journal - Depression, anxiety, catastrophising, and fear-avoidance beliefs are key "yellow flags" (YFs) that predict a poor outcome in back patients. Most surgeons...     

PLAG1 immunohistochemistry is a sensitive marker for pleomorphic adenoma: a comparative study with PLAG1 genetic abnormalities

Aims

Pleomorphic adenoma gene 1 (PLAG1) gene rearrangement is the most common genetic abnormality in pleomorphic adenoma (PA), resulting in overexpression of PLAG1 protein. PA and carcinoma ex pleomorphic adenoma (CA ex‐PA) can mimic various benign and malignant salivary gland tumours. The aims of this study are to evaluate the sensitivity and specificity of PLAG1 immunohistochemistry (IHC) in the differential diagnosis of PA and CA ex‐PA and to compare the PLAG1 immunohistochemical results to PLAG1 gene abnormalities as detected by fluorescence in‐situ hybridisation (FISH).

Methods and results

PLAG1 immunostaining was performed on 83 salivary gland tumours, including 23 PA, 15 CA ex‐PA and 45 other salivary gland tumours. In addition, PLAG1 FISH was performed in 44 cases for the presence of gene rearrangements/amplifications. The results showed high sensitivity of PLAG1 IHC in 96% of PA; however, discordant results between PLAG1 FISH abnormalities and IHC were noted in 15 of 44 cases (34%). Seven PA, four de‐novo myoepithelial carcinomas and one basal cell adenocarcinoma had negative FISH results, but were positive for IHC; while three salivary duct carcinomas (SDC) ex‐PA were positive for FISH but negative for IHC. PLAG1 IHC can differentiate CA ex‐PA from de‐novo SDC (P = 0.02), but not from de‐novo myoepithelial carcinoma. PLAG1 IHC is a sensitive marker for PA. This could be due to PLAG1 gene abnormalities beyond FISH resolution.

Conclusions

A negative PLAG1 IHC might be helpful in excluding a PA diagnosis. Interestingly, in the context of CA ex‐PA, FISH is more sensitive than IHC in detecting PLAG1 abnormalities.     

Inhibition of Calpain Prevents N-Methyl-D-aspartate-Induced Degeneration of the Nucleus Basalis and Associated Behavioral Dysfunction

N-Methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity is thought to underlie a variety of neurological disorders, and inhibition of either the NMDA receptor itself, or molecules of the intracellular cascade, may attenuate neurodegeneration in these diseases. Calpain, a calcium-dependent cysteine protease, has been identified as part of such an NMDA receptor-induced excitotoxic signaling pathway. The present study addressed the question of whether inhibition of calpain can prevent neuronal cell death and associated behavioral deficits in a disease-relevant animal model, which is based on excitotoxic lesions of the cholinergic nucleus basalis magnocellularis of Meynert. Excitotoxic lesions of the nucleus basalis with NMDA induced a markedly impaired performance in the novel object recognition test. Treatment with the calpain inhibitor, N-(1-benzyl-2-carbamoyl-2-oxoethyl)-2-[E-2-(4-diethlyaminomethylphenyl) ethen-1-yl]benzamide (A-705253), dose-dependently prevented the behavioral deficit. Subsequent analysis of choline acetyltransferase in the cortical mantle of the lesioned animals revealed that application of A-705253 dose-dependently and significantly attenuated cholinergic neurodegeneration. Calpain inhibition also significantly diminished the accompanying gliosis, as determined by immunohistochemical analysis of microglia activation. Finally, inhibition of calpain by A-705253 and the peptidic calpain inhibitor N-acetyl-Leu-Leu-Nle-CHO did not impair long-term potentiation in hippocampal slices, indicating that calpain inhibition interrupts NMDA excitotoxicity pathways without interfering with NMDA receptor-mediated signaling involved in cognition. We conclude that inhibition of calpains may represent a valuable strategy for the prevention of excitotoxicity-induced neuronal decline without interfering with the physiological neuronal functions associated with learning and memory processes. Thus, calpain inhibition may be a promising and novel approach for the treatment of various neurodegenerative disorders.     

Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies

Journal of Clinical Immunology - Six to 19% of critically ill COVID-19 patients display circulating auto-antibodies against type I interferons (IFN-AABs). Here, we establish a clinically applicable...