Smith, Michael A.

Abstract This post hoc analysis of the randomized, placebo‐controlled N‐MOmentum study (NCT02200770) of inebilizumab in neuromyelitis optica spectrum disorder (NMOSD) evaluated relationships between circulating B‐cell subsets and aquaporin‐4 immunoglobulin G (AQP4‐lgG) titers and attacks. Among participants receiving placebo, CD20 + and CD27 + B‐cell counts were modestly increased from the pre‐attack visit to attack; plasmablast/plasma cell gene signature was increased from baseline to the pre‐attack visit ( p = 0.016) and from baseline to attack ( p = 0.009). With inebilizumab treatment, B‐cell subset counts decreased and did not increase with attacks. No difference in change of AQP4‐IgG titers from baseline to time of attack was observed.

Remimazolam is an ultrashort acting intravenous sedative-hypnotic approved for procedural sedation. We report a series of 8 cases of radiographically placed gastrostomy tubes using remimazolam as the sole anesthetic agent. Interventional radiology (IR) gastrostomy tube placement entails anesthetizing often complex patients in a nonoperating room environment. All 8 patients reported here underwent successful gastrostomy tube placement without the need for conversion to general anesthesia. Remimazolam is a feasible option to sedate patients for gastrostomy tube placement in the IR suite.

Abstract BackgroundSelf-assembly of the amyloid-β (Aβ) peptide into aggregates, from small oligomers to amyloid fibrils, is fundamentally linked with Alzheimer’s disease (AD). However it is clear that not all forms of Aβ are equally harmful, and that linking a specific aggregate to toxicity also depends on the assays and model systems used [1, 2]. Though a central postulate of the amyloid cascade hypothesis, there remain many gaps in our understanding regarding the links between Aβ deposition and neurodegeneration.MethodsIn this study, we examined familial mutations of Aβ that increase aggregation and oligomerization, E22G and DE22, and induce cerebral amyloid angiopathy, E22Q and D23N. We also investigated synthetic mutations that stabilize dimerization, S26C, and a phospho-mimetic, S8E, and non-phospho-mimetic, S8A. To that end, we utilized BRI2-Aβ fusion technology and rAAV2/1 based somatic brain transgenesis in mice to selectively express individual mutant Aβ species in vivo . In parallel we generated PhiC31-based transgenic Drosophila melanogaster expressing wild type (WT) and Aβ40 and Aβ42 mutants, fused to the Argos signal peptide to assess the extent of Aβ42-induced toxicity as well as to interrogate the combined effect of different Aβ40 and Aβ42 species.ResultsWhen expressed in the mouse brain for 6 months, Aβ42 E22G, Aβ42 E22Q/D23N, and Aβ42WT formed amyloid aggregates consisting of some diffuse material as well as cored plaques, whereas other mutants formed predominantly diffuse amyloid deposits. Moreover, while Aβ40WT showed no distinctive phenotype, Aβ40 E22G and E22Q/D23N formed unique aggregates that accumulated in mouse brains. This is the first evidence that mutant Aβ40 overexpression leads to deposition under certain conditions. Interestingly, we found that mutant Aβ42 E22G, E22Q, and S26C, but not Aβ40, were toxic to the eye of Drosophila . In contrast, flies expressing a copy of Aβ40 (WT or mutants) in addition to Aβ42WT, showed improved phenotypes, suggesting possible protective qualities for Aβ40.ConclusionsThese studies suggest that some Aβ40 mutants form unique amyloid aggregates in mouse brains, despite protecting against Aβ42 toxicity in Drosophila , which highlights the significance of using different systems for a better understanding of AD pathogenicity and more accurate screening for new potential therapies.