Anti-REL Monoclonal antibody, clone 2SFMBI6

The Wisconsin Card Sorting Test (WCST) represents the gold standard for the neuropsychological assessment of executive function. However, very little is known about its reliability. In the current study, 146 neurological inpatients received the Modified WCST (M-WCST). Four basic measures (number of correct sorts, categories, perseverative errors, set-loss errors) and their composites were evaluated for split-half reliability. The reliability estimates of the number of correct sorts, categories, and perseverative errors fell into the desirable range (rel >= .90). The study therefore disclosed sufficiently reliable M-WCST measures, fostering the application of this eminent psychological test to neuropsychological assessment. Our data also revealed that the M-WCST possesses substantially better psychometric properties than would be expected from previous studies of WCST test-retest reliabilities obtained from non-patient samples. Our study of split-half reliabilities from discretionary construed and from randomly built M-WCST splits exemplifies a novel approach to the psychometric foundation of neuropsychology.

BackgroundThe prevalence of antibiotic resistance is increasing, and multidrug-resistant Pseudomonas aeruginosa has been identified as a serious threat to human health. The production of beta-lactamase is a key mechanism contributing to imipenem resistance in P. aeruginosa. Relebactam is a novel beta-lactamase inhibitor, active against class A and C beta-lactamases, that has been shown to restore imipenem susceptibility. In a series of studies, we assessed the interaction of relebactam with key mechanisms involved in carbapenem resistance in P. aeruginosa and to what extent relebactam might overcome imipenem non-susceptibility.ResultsRelebactam demonstrated no intrinsic antibacterial activity against P. aeruginosa, had no inoculum effect, and was not subject to efflux. Enzymology studies showed relebactam is a potent (overall inhibition constant: 27nM), practically irreversible inhibitor of P. aeruginosa AmpC. Among P. aeruginosa clinical isolates from the SMART global surveillance program (2009, n=993; 2011, n=1702; 2015, n=5953; 2016, n=6165), imipenem susceptibility rates were 68.4% in 2009, 67.4% in 2011, 70.4% in 2015, and 67.3% in 2016. With the addition of 4 mu g/mL relebactam, imipenem susceptibility rates increased to 87.6, 86.0, 91.7, and 89.8%, respectively. When all imipenem-non-susceptible isolates were pooled, the addition of 4 mu g/mL relebactam reduced the mode imipenem minimum inhibitory concentration (MIC) 8-fold (from 16 mu g/mL to 2 mu g/mL) among all imipenem-non-susceptible isolates. Of 3747 imipenem-non-susceptible isolates that underwent molecular profiling, 1200 (32%) remained non-susceptible to the combination imipenem/relebactam (IMI/REL); 42% of these encoded class B metallo-beta-lactamases, 11% encoded a class A GES enzyme, and no class D enzymes were detected. No relationship was observed between alleles of the chromosomally-encoded P. aeruginosa AmpC and IMI/REL MIC.ConclusionsIMI/REL exhibited potential in the treatment of carbapenem-resistant P. aeruginosa infections, with the exception of isolates encoding class B, some GES alleles, and class D carbapenemases.