Noradrenergic depletion causes sex specific alterations in the endocannabinoid system in the Murine prefrontal cortex.

Brain endocannabinoids (eCB), acting primarily via the cannabinoid type 1 receptor (CB1r), are involved in the regulation of many physiological processes, including behavioral responses to stress. A significant neural target of eCB action is the stress-responsive norepinephrine (NE) system, whose dysregulation is implicated in myriad psychiatric and neurodegenerative disorders. Using Western blot analysis, the protein expression levels of a key enzyme in the biosynthesis of the eCB 2-arachidonoylglycerol (2-AG), diacylglycerol lipase-α (DGL-α), and two eCB degrading enzymes monoacylglycerol lipase (MGL) and fatty acid amide hydrolase (FAAH) were examined in a mouse model that lacks the NE-synthesizing enzyme, dopamine ß-hydroxylase (DßH-knockout, KO) and in rats treated with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4). In the prefrontal cortex (PFC), DGL-α protein expression was significantly increased in male and female DßH-KO mice (P < 0.05) compared to wild-type (WT) mice. DßH-KO male mice showed significant decreases in FAAH protein expression compared to WT male mice. Consistent with the DßH-KO results, DGL-α protein expression was significantly increased in male DSP-4-treated rats (P < 0.05) when compared to saline-treated controls. MGL and FAAH protein expression levels were significantly increased in male DSP-4 treated rats compared to male saline controls. Finally, we investigated the anatomical distribution of MGL and FAAH in the NE containing axon terminals of the PFC using immunoelectron microscopy. MGL was predominantly within presynaptic terminals while FAAH was localized to postsynaptic sites. These results suggest that the eCB system may be more responsive in males than females under conditions of NE perturbation, thus having potential implications for sex-specific treatment strategies of stress-related psychiatric disorders.

Improving quality and safety in paediatric spinal surgery: the team approach.

Aims: The aim of this study was to evaluate improvements in the quality and safety of paediatric spinal surgery following the implementation of a specialist Paediatric Spinal Surgical Team (PSST) in the operating theatre. Patients and Methods: A retrospective consecutive case study of paediatric spinal operations before (between January 2008 and December 2009), and after (between January 2012 and December 2013) the implementation of PSST, was performed. A comparative analysis of outcome variables including surgical site infection (SSI), operating time (ORT), blood loss (BL), length of stay (LOS), unplanned staged procedures (USP) and transfusion rates (allogenic and cell-saver) was performed between the two groups. The rate of complications during the first two postoperative years was also compared between the groups. Results: There were 130 patients in the pre-PSST group and 277 in the post-PSST group. The age, gender, body mass index (BMI), preoperative Cobb angle of the major curve and the number of levels involved were similar between the groups. There were statistically significant differences in SSI, ORT, LOS, allogenic blood transfusion volume (ABTV), and USPs between the groups. There was a 94% decrease in the rate of SSI's in the post-PSST group. Patients in the post-PSST group had a mean reduction in ORT of 53 minutes (sd 7.7) (p = 0.013), LOS by 5.4 days (sd 1.8) (p = 0.019), and ABTV by 226.3 ml (sd 28.4) (p < 0.001). There were significantly more USPs in the pre-PSST group (6.2%) compared with the post-PSST group (2.9%) (p = 0.001). Multivariate regression showed that the effect of PSST remained significant for ORT, LOS, BL, ABVT and cell-saver amount transfused (p = 0.0001). The odds of having a SSI were tenfold higher and the odds of receiving a blood transfusion were 2.4 times higher, respectively, in the pre-PSST group (p = 0.004 and p = 0.011). The rate of complications within the first two postoperative years was significantly higher in the pre-PSST group (13.1%) compared with the post-PSST group (4.3%) (p < 0.001). Conclusion: The implementation of a PSST in the operating theatre significantly improves the outcomes in paediatric spinal surgery. Cite this article: Bone Joint J 2018;100-B:493-8.