Assembly PCR synthesis of optimally designed, compact, multi-responsive promoters suited to gene therapy application

MRC-DTA studentship award British Pharmacological Society Integrative Awar

Cameroonian spice extracts modulate molecular mechanisms relevant to cardiometabolic diseases in sw 872 human liposarcoma cells

The molecular pathophysiology of cardiometabolic diseases is known to be influenced by dysfunctional ectopic adipose tissue. In addition to lifestyle improvements, these conditions may be managed by novel nutraceutical products. This study evaluatedthe effects of 11 Cameroonian medicinal spice extracts on triglyceride accumulation, glucose uptake, reactive oxygen species (ROS) production and interleukin secretion in SW 872 human adipocytes after differentiation with 100 μM oleic acid. Triglyceride content was significantly reduced by all spice extracts. Glucose uptake was significantly increased by Tetrapleura tetraptera, Aframomum melegueta and Zanthoxylum leprieurii. Moreover, Xylopia parviflora, Echinops giganteus and Dichrostachys glomerata significantly reduced the production of ROS. Concerning pro‐inflammatory cytokine secretion, we observed that Tetrapleura tetraptera, Echinops giganteus, Dichrostachys glomerata and Aframomum melegueta reduced IL‐6 secretion. In addition, Xylopia parviflora, Monodora myristica, Zanthoxylum leprieurii, and Xylopia aethiopica reduced IL‐8 secretion, while Dichrostachys glomerata and Aframomum citratum increased it. These findings highlight some interesting properties of these Cameroonian spice extracts in the modulation of cellular parameters relevant to cardiometabolic diseases, which may be further exploited, aiming to develop novel treatment options for these conditions based on nutraceutical products

Cationic (eta(6)-arene)tricarbonylmanganese linked to ferrocene complexes

Palladium-catalyzed Sonogashira coupling reactions of the neutral [eta(5)(1-5)-(1-chloro-4-methoxycyclohexa-2,4-dienyl)]tricarbonylmangane se(l) (2) and 2-bromo-5-{[eta(5)(1-5)-(4-methoxycyclohexa-2,4-dienylltricarbonylmangan ese(I)}thiophene (13) with the ethynylferrocene derivative 5 give the dinuclear complexes 1-(ferrocenylethynyl)[eta(5)(1-5)-(4-methoxycyclohexa2,4-dienyl)]tricarb onylmanganese(I) (6) and 2-(ferrocenylethynyl)-5-[eta(5)(1-5)-(4-methoxycyclohexa-2,4-dienyl)tric arbonylmanganese]thiophene (10). Similarly, condensation of 2 with 2-(ferrocenylethynyl)-5-ethynylthiophene (18) affords the dinuclear complex 19. These complexes are valuable precursors, upon hydride abstraction, of the corresponding eta(6)-arene cations 7, 11, and 20. The structure of one of them, 1-(ferrocenylethynyl)[eta(6)(1-6)-(4-methoxybenzene)]tricarbonylmanganes e(I) tetrafluoroborate (7), has been investigated by X-ray diffraction

World Heart Federation criteria for echocardiographic diagnosis of rheumatic heart disease: an evidence-based guideline

Over the past 5 years, the advent of echocardiographic screening for rheumatic heart disease (RHD) has revealed a higher RHD burden than previously thought. In light of this global experience, the development of new international echocardiographic guidelines that address the full spectrum of the rheumatic disease process is opportune. Systematic differences in the reporting of and diagnostic approach\ud to RHD exist, reflecting differences in local experience and disease patterns. The World Heart Federation\ud echocardiographic criteria for RHD have, therefore, been developed and are formulated on the basis of the best available evidence. Three categories are defined on the basis of assessment by 2D, continuous-wave,and color-Doppler echocardiography: 'definite RHD', 'borderline RHD', and 'normal'. Four subcategories of 'definite RHD' and three subcategories of 'borderline RHD' exist, to reflect the various disease patterns. The morphological features of RHD and the criteria for pathological mitral and aortic regurgitation are also defined. The criteria are modified for those aged over 20 years on the basis of the available evidence. The standardized criteria aim to permit rapid and consistent identification of individuals with RHD without a clear history of acute rheumatic fever and hence allow enrollment into secondary prophylaxis programs. However, important unanswered questions remain about the importance of subclinical disease (borderline or definite RHD on echocardiography without a clinical pathological murmur), and about the practicalities of implementing screening programs. These standardized criteria will help enable new studies to be designed to evaluate the role of echocardiographic screening in RHD control

Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data

Background: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care. Methods: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered. Findings: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09–2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75–3·10, p<0·0001) versus standard care. However, outcomes were significantly better for patients who did not receive GA versus those who received GA (covariate-adjusted cOR 1·53, 95% CI 1·14–2·04, p=0·0044). The risk of bias and variability between studies was assessed to be low. Interpretation: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons