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Background: Deep brain stimulation is explored as a new intervention for treatment-resistant substance use dependence. A candidate brain region is the nucleus accumbens, due to its involvement in reward and motivation. This study aimed to explore effects of NAcore and NAshell deep brain stimulation on aspects of heroin taking and seeking in a self-administration model for rats., Methods: NAcore and NAshell deep brain stimulation was applied during 25 or 100 µg/kg/infusion heroin self-administration on an FR4 schedule of reinforcement and during cue- and heroin-induced reinstatement. In a separate group, effects of NAcore deep brain stimulation on heroin self-administration on a progressive ratio schedule and the first extinction session were examined., Results: NAcore and NAshell deep brain stimulation did not alter heroin self-administration on an FR4 schedule. NAcore deep brain stimulation decreased cue - but not drug-induced reinstatement of heroin seeking, whereas NAshell deep brain stimulation did not affect reinstatement responding. In the second experiment, NAcore deep brain stimulation reduced responding during a progressive ratio schedule of heroin reinforcement. Finally, deep brain stimulation facilitated extinction from day 1 throughout the course of extinction learning., Conclusion: Taken together, the differential effects of NAcore and NAshell deep brain stimulation on heroin taking and seeking are in line with the distinct functional roles of these sub-regions therein. Conditioned cues have been shown to be very powerful stimuli for the persistence of addiction and relapse to drug use. Therefore, the present findings that NAcore deep brain stimulation decreases motivation for heroin taking and cue-conditioned behaviour and facilitates extinction learning are very promising, supporting the positive findings from clinical case studies., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2017.)

Study Design: Interobserver reliability study., Introduction: A scale was developed to measure the severity of stenosing tenosynovitis: the Amsterdam Severity Scale in Stenosing Tenosynovitis (ASSiST)., Purpose of the Study: To study the interobserver reliability of the ASSiST., Methods: Patients suffering from various impairments in hand function were referred to our outpatient hand clinic. The grading of stenosing tenosynovitis was assessed independently. The observers were blinded for each other's results. The ASSiST distinguishes between a nodular and a diffuse form. The severity was graded from grades 0 to 3., Results: Kappa coefficient for the distinction between the four grades was 0.72 (95% confidence interval [CI] 0.59-0.85) and for the distinction between the nodular and the diffuse forms 0.16 (95% CI 0.13-0.18)., Conclusion: The ASSiST can be used to reliably assess the severity of stenosing tenosynovitis in both nodular and diffuse forms, but it does not differentiate between these two forms., Level of Evidence: Not applicable.

Cysteine 39 of Escherichia coli primase is the most chemically reactive cysteine. Its high chemical reactivity is likely due to its proximity to primase's zinc, which is probably ligated to the adjacent residues 40-62. The zinc may stabilize the deprotonated form of cysteine 39 to make it chemically reactive. Primase is rapidly, site-specifically modified by fluorescein maleimide (FM) at this cysteine. Modification with FM at this residue does not lead to any activity loss in a coupled RNA/DNA synthesis assay, indicating that it is not a catalytically essential residue. In contrast, iodoacetamidefluorescein (IAF) modifies cysteine 39 more slowly and stoichiometrically inhibits activity. It was not clear why these two similar fluorescent dyes should have such different inhibitory effects when attached to the same cysteine. The IAF inhibition must be due to some property of the link between the fluorescein and the cysteine because that is how it differs from FM. The pKa's of the fluoresceins from both FM- and IAF-modified primase are strongly shifted to lower values (approximately 5.4) compared to free fluorescein. These results strongly suggest that the deprotonated form of the fluoresceins are stabilized on primase by a strong interaction with the adjacent zinc in the zinc finger motif. The ability to place a noninhibitory FM at this site will be of great assistance in fluorescence energy transfer studies since the distances established to cysteine 39 will reflect the distance to the essential zinc finger motif.