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Clinical practice guidelines are a valuable resource aiding medical decision-making based on scientific evidence. In anaesthesia, guidelines are increasing in both number and scope, influencing individual practice and shaping local departmental policy. The aim of this review is to assess the quality of clinical practice guidelines published in high impact anaesthesia journals over the past 5 yr using the internationally validated Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. A literature search was conducted in Scopus to identify all guidelines published in the top 10 anaesthesia journals as per Clarivate Analytics Impact Factor from 2016 and 2020. Fifty-one guidelines were included for analysis by five independent appraisers using AGREE II. Each guideline was assessed across six domains and 23 items. Individual domain scores were calculated with a threshold agreed via consensus to represent high-quality guidelines. There was a significant increase in overall score over time (P=0.041), driven by Domain 3 (Rigour of Development, P=0.046). The raw overall score for Domain 3, however, was low. The other domains performed as expected based on previous studies, with Domains 1, 4, and 6 achieving high scores and Domains 2 and 5 incurring poor ratings. Most guidelines studied involved international collaboration but emerged from a single professional society. Use of an appraisal tool was stated as high but poorly detailed. The improvement in the overall score of guidelines and rigour of development is promising; however, only seven guidelines met high-quality criteria, suggesting room for improvement for the overall integrity of guidelines in anaesthesia.

Background Ethanol causes developmental neurotoxicity partly by blocking adhesion mediated by the L1 neural cell adhesion molecule. This action of ethanol is antagonized by femtomolar concentrations of the neuropeptide NAPVSIPQ (NAP), an active fragment of the activity-dependent neuroprotective protein (ADNP). How femtomolar concentrations of NAP antagonize millimolar concentrations of ethanol is unknown. L1 sensitivity to ethanol requires L1 association with ankyrin-G; therefore, we asked whether NAP promotes the dissociation of ankyrin-G and L1. Methods L1–ankyrin-G association was studied using immunoprecipitation, Western blotting, and immunofluorescence in NIH/3T3 cells transfected with wild-type and mutated human L1 genes. Phosphorylation of the ankyrin binding motif in the L1 cytoplasmic domain was studied after NAP treatment of intact cells, rat brain homogenates, and purified protein fragments. Results Femtomolar concentrations of NAP stimulated the phosphorylation of tyrosine-1229 (L1-Y1229) at the ankyrin binding motif of the L1 cytoplasmic domain, leading to the dissociation of L1 from ankyrin-G and the spectrin-actin cytoskeleton. NAP increased the association of L1 and EphB2 and directly activated EphB2 phosphorylation of L1-Y1229. These actions of NAP were reproduced by P7A-NAP, a NAP variant that also blocks the teratogenic actions of ethanol, but not by I6A-NAP, which does not block ethanol teratogenesis as potently. Finally, knockdown of EPHB2 prevented ethanol inhibition of L1 adhesion in NIH/3T3 cells. Conclusions NAP potently antagonizes ethanol inhibition of L1 adhesion by stimulating EphB2 phosphorylation of L1-Y1229. EphB2 plays a critical role in synaptic development; its potent activation by NAP suggests that ADNP may mediate synaptic development partly by activating EphB2.

A novel anaerobic, hyperthermophilic archaeon was isolated from a mud volcano in the Salton Sea geothermal system in southern California, USA. The isolate, named strain 521T, grew optimally at 90 °C, at pH 5.5–7.3 and with 0–2.0 % (w/v) NaCl, with a generation time of 10 h under optimal conditions. Cells were rod-shaped and non-motile, ranging from 2 to 7 µm in length. Strain 521T grew only in the presence of thiosulfate and/or Fe(III) (ferrihydrite) as terminal electron acceptors under strictly anaerobic conditions, and preferred protein-rich compounds as energy sources, although the isolate was capable of chemolithoautotrophic growth. 16S rRNA gene sequence analysis places this isolate within the crenarchaeal genus Pyrobaculum . To our knowledge, this is the first Pyrobaculum strain to be isolated from an anaerobic mud volcano and to reduce only either thiosulfate or ferric iron. An in silico genome-to-genome distance calculator reported