Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an immune-mediated disease characterized by a complex neuropsychiatric syndrome in association with an antibody-mediated decrease of NMDAR. About 85% of patients respond to immunotherapy (and removal of an associated tumour if it applies), but it often takes several months or more than 1 year for patients to recover. There are no complementary treatments, beyond immunotherapy, to accelerate this recovery. Previous studies showed that SGE-301, a synthetic analogue of 24(S)-hydroxycholesterol, which is a potent and selective positive allosteric modulator of NMDAR, reverted the memory deficit caused by phencyclidine (a non-competitive antagonist of NMDAR), and prevented the NMDAR dysfunction caused by patients’ NMDAR antibodies in cultured neurons. ARN509 An advantage of SGE-301 is that it is optimized for systemic delivery such that plasma and brain exposures are sufficient to modulate NMDAR activity. Here, we used SGE-301 to confirm that in cultured neurons iogenic effects (memory, synaptic NMDAR, long-term potentiation) were prevented in the animals treated with SGE-301, despite this compound not antagonizing antibody binding. Additional investigations on the potential mechanisms related to these SGE-301 effects showed that (i) in cultured neurons SGE-301 prolonged the decay time of NMDAR-dependent spontaneous excitatory postsynaptic currents suggesting a prolonged open time of the channel; and (ii) it significantly decreased, without fully preventing, the internalization of antibody-bound receptors suggesting that additional, yet unclear mechanisms, contribute in keeping unchanged the surface NMDAR density. Overall, these findings suggest that SGE-301, or similar NMDAR modulators, could potentially serve as complementary treatment for anti-NMDAR encephalitis and deserve future investigations.

There is an increasing interest in the quality of life (QoL) evaluation following video-assisted thoracoscopic anatomical lung resection or stereotactic ablative body radiotherapy for early-stage non-small-cell lung cancer (NSCLC). A qualitative interview study was conducted to gain insight into the optimal methods of assessing and discussing QoL in clinical practice.

A prospective observational longitudinal study of patients with early-stage NSCLC was conducted where repeated QoL measures were administered either online or on paper. A subset of participants was invited for qualitative interviews after the 6-month assessment or at the end of the study. The semi-structured interviews were transcribed verbatim and thematically analysed.

Twenty-three patients were interviewed. Generally, patients were content with recruitment and data collection procedures. Most opted to complete the assessments on paper instead of online; this choice was influenced by the level of technology literacy. Some found the questice.

Reducing Neisseria gonorrhoeae colonies in the oropharynx is a viable solution to minimize the transmission of this bacterium amongst individuals.

A strategy involving the electrostatic interaction between a common antiseptic and a discontinued antibiotic (i.e. octenidine and carbenicillin) was evaluated as a potential treatment for gonorrhoea. Octenidine/carbenicillin is a novel group of uniform materials based on organic salts (GUMBOS) with inherent in vitro antibacterial activity that comes from its parent antiseptic and antibacterial ions, octenidine and carbenicillin, respectively.

Antibacterial activities for octenidine dihydrochloride, disodium carbenicillin, octenidine/carbenicillin and stoichiometrically equivalent 11 octenidine dihydrochloride to disodium carbenicillin were assessed using the Kirby-Bauer disc diffusion assay for N. gonorrhoeae (ATCC 49226) and three clinical isolates. Predictive permeability using the Parallel Artificial Membrane Permeability Assay and cytotoxicity against HeLa cells was also evaluated.

Additive in vitro antibacterial activities against N. gonorrhoeae were observed in this study, which suggests octenidine/carbenicillin could be a useful agent in reducing N. gonorrhoeae transmission and minimizing gonorrhoea infections. Octenidine/carbenicillin also exhibited bioequivalence to azithromycin and doxycycline, two currently prescribed antibiotics. Likewise, octenidine/carbenicillin had improved predicted permeability compared with octenidine dihydrochloride.

Antimicrobial GUMBOS synthesized in this study could be used as an adjunctive treatment approach to current drug therapies for oropharyngeal gonorrhoea infection control and prevention.

Antimicrobial GUMBOS synthesized in this study could be used as an adjunctive treatment approach to current drug therapies for oropharyngeal gonorrhoea infection control and prevention.

The incidence of antimicrobial-resistant Neisseria gonorrhoeae (GC) is rising in Canada; however, antimicrobial resistance (AMR) surveillance data are unavailable for infections diagnosed directly from clinical specimens by nucleic acid amplification tests (NAATs), representing over 80% of diagnoses. We developed a set of 10 improved molecular assays for surveillance of GC-AMR and prediction of susceptibilities in NAAT specimens.

Multiplex real-time PCR (RT-PCR) assays were developed to detect SNPs associated with cephalosporin (ponA, porB, mtrR -35delA, penA A311V, penA A501, N513Y, G545S), ciprofloxacin (gyrA S91, parC D86/S87/S88) and azithromycin [23S (A2059G, C2611T), mtrR meningitidis-like promoter] resistance. The assays were validated on 127 gonococcal isolates, 51 non-gonococcal isolates and 50 NAATs with matched culture isolates. SNPs determined from the assay were compared with SNPs determined from in silico analysis of WGS data. MICs were determined for culture isolates using the agar dilution method.

SNP analysis of the 50 NAAT specimens had 96% agreement with the matched culture RT-PCR analysis. When compared with MICs, presence of penA A311V or penA A501 and two or more other SNPs correlated with decreased susceptibility and presence of three or more other SNPs correlated with intermediate susceptibility to cephalosporins; presence of any associated SNP correlated with ciprofloxacin or azithromycin resistance. NAAT-AMR predictions correlated with matched-culture cephalosporin, ciprofloxacin and azithromycin MICs at 94%, 100% and 98%, respectively.

We expanded molecular tests for N. gonorrhoeae AMR prediction by adding new loci and multiplexing reactions to improve surveillance where culture isolates are unavailable.

We expanded molecular tests for N. gonorrhoeae AMR prediction by adding new loci and multiplexing reactions to improve surveillance where culture isolates are unavailable.