The modulation effect of longitudinal acupuncture on resting state functional connectivity in knee osteoarthritis patients

Recent advances in brain imaging have contributed to our understanding of the neural activity associated with acupuncture treatment. In this study, we investigated functional connectivity across longitudinal acupuncture treatments in older patients with knee osteoarthritis (OA). Over a period of 4 weeks (six treatments), we collected resting state functional magnetic resonance imaging (fMRI) scans from 30 patients before and after their first, third and sixth treatments. Clinical outcome showed a significantly greater pain subscore on the Knee Injury and Osteoarthritis Outcome Score (KOOS) (indicative of improvement) with verum acupuncture than with sham acupuncture. Independent component analysis (ICA) of the resting state fMRI data showed that the right frontoparietal network (rFPN) and the executive control network (ECN) showed enhanced functional connectivity (FC) with the rostral anterior cingulate cortex/medial prefrontal cortex, a key region in the descending pain modulatory system, in the verum groups as compared to the sham group after treatments. We also found that the rFPN connectivity with the left insula is (1) significantly associated with changes in KOOS pain score after treatments, and (2) significantly enhanced after verum acupuncture treatments as compared to sham treatment. Analysis of the acupuncture needle stimulation scan showed that compared with sham treatment, verum acupuncture activated the left operculum/insula, which also overlaps with findings observed in resting state analysis. Our results suggest that acupuncture may achieve its therapeutic effect on knee OA pain by modulating functional connectivity between the rFPN, ECN and the descending pain modulatory pathway. Clinical trial number: NCT0107939

Does the CHA2DS2-Vasc score predict procedural and short-term outcomes in patients undergoing transcatheter aortic valve implantation?

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is associated with periprocedural and postprocedural morbidity and mortality. Currently, there is a paucity of risk stratification models for potential TAVI candidates. We employed the CHA(2)DS(2)-Vasc score to quantify the risk of 30-day mortality and morbidity in patients undergoing TAVI. METHODS AND RESULTS: A retrospective analysis of registry data for consecutive patients undergoing TAVI at 3 tertiary centres in Northwest England between 2008 and 2013. The CHA(2)DS(2)-Vasc score and its modification—the R(2)CHA(2)DS(2)-Vasc score, which includes pre-existing renal impairment and pre-existing conduction abnormality (right bundle branch block/left bundle branch block, RBBB/LBBB)—were calculated for all patients. A total of 313 patients with a mean age of 80 (79.1–80.8) years underwent TAVI. The implanted devices were either the CoreValve or the Edwards-SAPIEN prosthesis. The 30-day mortality was 14.3% in those with a CHA(2)DS(2)-Vasc score ≥6, whereas it was only 6.2% in those with a score <6 (p=0.04). Using the R(2)-CHA(2)DS(2)-Vasc score, the difference was more pronounced with a 30-day mortality of 22.6% in those patients with an R(2)-CHA(2)DS(2)-Vasc score ≥7 compared to 6.0% in those with a R(2)-CHA(2)DS(2)-Vasc score <7 (p=0.001). In multivariable Cox regression analyses, there was a significant and independent relationship between the CHA(2)DS(2)-Vasc score (hazard ratio (HR)= 2.71, (1.01 to 7.31); p<0.05) and the modified R(2)CHA(2)DS(2)-Vasc score (HR=4.27 (1.51 to 12.07); p=0.006) with 30-day mortality. CONCLUSIONS: Our study demonstrates the potential use of the CHA(2)DS(2)-Vasc or the R(2)CHA(2)DS(2)-Vasc score to quantify the risk of mortality in patients undergoing TAVI. This could have significant implications in terms of clinical as well as patients’ decision-making

Synthesis of heterocyclic compounds via gold-catalysed enyne rearrangements

Syntheses of heterocycles using different gold-catalysed rearrangements of enynes are discussed in this chapter. The term skeletal rearrangement has been used in a broad sense to include reactions involving cyclopropyl gold carbene intermediates formed by initial enyne cyclisation, which can undergo many different transformations to give a wide range of heterocyclic structures. Other transformations involving rearrangement of propargylic esters and [3,3]-rearrangement (concerted or stepwise comprising metallic intermediates), as well as special cases, have also been covered. References to earlier work in this area and to recent reviews have been included, but the focus of the chapter is to present recent developments, interesting cases and an overview on how subtle differences in the enyne starting materials, the catalyst used or the reaction conditions can alter the reaction pathway increasing the structural diversity towards complex heterocyclic structures of high value

A gold-catalysed enantioselective Cope rearrangement of achiral 1,5-dienes

Since the discovery of the Cope rearrangement in the 1940s, no asymmetric variant of the rearrangement of achiral 1,5-dienes has emerged, despite the successes that have been achieved with its heteroatom variants (Claisen, aza-Cope, etc.). This article reports the first example of an enantioselective Cope reaction that starts from an achiral diene. The new gold(I) catalyst derived from double Cl(−)-abstraction of ((S)-3,5-xylyl-PHANEPHOS(AuCl)(2)), has been developed for the sigmatropic rearrangement of alkenyl-methylenecyclopropanes. The reaction proceeds at low temperature and the synthetically useful vinylcyclopropane products are obtained in high yield and enantioselectivity. Density functional theory calculations predict that: (1) the reaction proceeds via a cyclic carbenium ion intermediate, (2) the relief of strain in the methylenecyclopropane moiety provides the thermodynamic driving force for the rearrangement and (3) metal complexation of the transition-state structure lowers the rearrangement barriers