Sevoflurane Anesthesia Improves Cognitive Performance in Mice, but Does Not Influence In Vitro Long-Term Potentation in Hippocampus CA1 Stratum Radiatum

BACKGROUND: Whether the occurrence of postoperative cognitive dysfunction is a result of the effects of surgery or anesthesia is under debate. In this study, we investigated the impact of sevoflurane anesthesia on cognitive performance and cellular mechanisms involved in learning and memory. METHODS: Male C57Bl6/J mice (4–5 months) were exposed to one minimum alveolar concentration sevoflurane for two hours. After 24 h, cognitive performance of mice was assessed using the modified hole board test. Additionally, we evaluated hippocampal long-term potentiation and expression levels of different receptor subunits by recording excitatory postsynaptic field potentials and using the western blot technique, respectively. Non-anesthetized mice served as controls. RESULTS: In anesthetized mice, neither cognitive performance nor long-term potentiation was impaired 24 h after anesthesia. Interestingly, sevoflurane anesthesia induced even an improvement of cognitive performance and an elevation of the expression levels of N-methyl-D-aspartate (NMDA) receptor type 1 and 2B subunits in the hippocampus. CONCLUSIONS: Since NMDA receptor type 1 and 2B subunits play a crucial role in processes related to learning and memory, we hypothesize that sevoflurane-induced changes in NMDA receptor subunit composition might cause hippocampus-dependent cognitive improvement. The data of the present study are in favor of a minor role of anesthesia in mediating postoperative cognitive dysfunction

Subventricular zone involvement is associated with worse outcome in glioma WHO grade 2 depending on molecular markers

Neural stem cells within the subventricular zone were identified as cells of origin driving growth of high-grade gliomas, and anatomical involvement of the subventricular zone has been associated with an inferior clinical outcome. Whether the association between poor outcome and subventricular zone involvement also applies to glioma of lower grades is unclear. We therefore analysed a retrospective cohort of 182 patients with glioma grade 2 (according to the WHO 2016 classification) including 78 individuals (43%) with subventricular zone involvement. Patients with and without subventricular zone involvement did not differ in regard to demographics, histopathology, and molecular markers. Notably, subventricular zone involvement was a negative prognostic marker for malignant progression and overall survival on uni- and multivariate analysis. When patients were stratified according to the cIMPACT-NOW update 6, subventricular zone involvement was negatively associated with outcome in IDH-wildtype astrocytomas and 1p19q-codeleted oligodendrogliomas but not in IDH-mutant astrocytomas. Collectively, subventricular zone involvement may represent a risk factor for worse outcome in glioma WHO grade 2 depending on the molecular tumor signature. The present data confirm the relevance of molecular glioma classifications as proposed by the cIMPACT-NOW update 6. These findings warrant evaluation in prospective cohorts

Managing risks to drivers in road transport

This report presents a number of case studies in managing risks to road transport drivers. The cases feature a variety of initiatives and interventions to protect drivers.In the road transport sector, as with any other, it is important to pay attention to working conditions in order to ensure a skilled and motivated workforce. Certain characteristics of the sector make it more difficult to practice risk management than in other sectors. But by taking account of how the sector operates in practice, and the characteristics of drivers themselves and the way they work, risks can be successfully manage

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Multidimensional exploration of blood pressure genetics and the epithelial Na⁺ channel

The epithelial Na⁺ channel (ENaC) is part of the mechanism for fine-tuning Na⁺ reabsorption and blood pressure in the distal nephron of the kidney. The ‘thumb’ domain, interacts with the pore at its base, and interacts with the ‘finger’ domain at its tip. By crosslinking the sites between the thumb and finger domains, we show that one of the finger domain cysteines in the α subunit and both of the finger domain cysteines in the γ subunit lie near the finger–thumb domain interface. We also observed functional asymmetry between the α and γ subunits: crosslinking the α subunit finger–thumb interface only inhibited ENaC currents, while crosslinking the γ subunit finger–thumb interface activated or inhibited currents in a crosslinker-length-dependent manner. Gain-of-function or loss-of-function ENaC mutations have profound effects on renal Na⁺ reabsorption and blood pressure. While several ENaC single nucleotide variants (SNVs) with large effect sizes have been identified, the impact of rare ENaC SNVs on blood pressure has not been assessed. Using a large genomic sequencing database, TOPMed, we are able to explore the effects of rare ENaC variants sequenced from 62,784 individuals. We identified 38 SNVs that affect ENaC expression or function. Using burden tests and SKAT, we analyzed the burden of rare ENaC variants associated with blood pressure, stroke, and CKD from a subset of TOPMed studies. Our results indicate that rare ENaC variants are associated with blood pressure phenotypes. Hypertension is a significant public health concern and affects over a quarter of adults globally. It is a risk factor for cardiovascular disease, stroke, and kidney disease; therefore, it is a leading contributor to mortality. 901 blood pressure associated loci have been identified in the literature; yet, these variants only explain 11% of blood pressure variance. We have performed GWAS for five blood pressure traits in a population of 3,400 individuals from Samoa. Exploring blood pressure genetics through GWAS in this population isolate may provide additional insights into the mechanisms controlling blood pressure that are unseen in other populations as well as how far reaching some aspects of shared blood pressure genetics can be