Signatures of anthocyanin metabolites identified in humans inhibit biomarkers of vascular inflammation in human endothelial cells

Scope The physiological relevance of contemporary cell culture studies is often perplexing, given the use of unmetabolized phytochemicals at supraphysiological concentrations. We investigated the activity of physiologically relevant anthocyanin metabolite signatures, derived from a previous pharmacokinetics study of 500 mg 13C5-cyanidin-3-glucoside in 8 healthy participants, on soluble vascular adhesion molecule-1 (VCAM-1) and interleukin-6 (IL-6) in human endothelial cells. Methods and results Signatures of peak metabolites (previously identified at 1, 6 and 24 h post-bolus) were reproduced using pure standards and effects were investigated across concentrations ten-fold lower and higher than observed mean (<5 μM) serum levels. Tumor necrosis factor-α (TNF-α)-stimulated VCAM-1 was reduced in response to all treatments, with maximal effects observed for the 6 h and 24 h profiles. Profiles tested at ten-fold below mean serum concentrations (0.19-0.44 μM) remained active. IL-6 was reduced in response to 1, 6 and 24 h profiles, with maximal effects observed for 6 h and 24 h profiles at concentrations above 2 μM. Protein responses were reflected by reductions in VCAM-1 and IL-6 mRNA, however there was no effect on phosphorylated NFκB-p65 expression. Conclusion Signatures of anthocyanin metabolites following dietary consumption reduce VCAM-1 and IL-6 production, providing evidence of physiologically relevant biological activity

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

THE MECHANISM OF THE OPTOGALVANIC EFFECT IN A HOLLOW-CATHODE DISCHARGE

Il y a deux mécanismes, différents de manière significative, qui sont proposés pour rendre compte de l'effet optogalvanique dans une décharge de cathode creuse : (1) L'excitation laser des atomes sur un état électronique élevé conduit à l'ionisation des atomes excités et à une augmentation de la conductivité dans la décharge. (2) L'excitation laser des atomes sur un état électronique élevé pertube l'équilibre préétabli entre la température électronique et la température d'excitation atomique. Les collisions superélastiques entre les électrons et les atomes excités restituent cet équilibre avec pour résultat que l'excès d'énergie augmente la température électronique, et, par conséquent, augmente la conductivité de la décharge. Ces deux mécanismes, sans aucun doute, existent simultanément et nous devons déterminer leur importance relative pour différentes conditions de fonctionnement de la décharge et de l'excitation. Ceci est important en raison des schémas d'excitation qui ont été proposés pour l'enrichissement isotopique par laser dans une décharge de cathode creuse. Pour que ces projets aboutissent, le mécanisme (1) doit être prédominant. Nous avons mesuré le signal optogalvanique, la concentration d'uranium, l'impédance de la décharge et la température électronique en fonction du courant de décharge d'une cathode creuse à uranium emplie de néon. Les caractéristiques de fonctionnement de la cathode creuse sont utilisées comme paramètres d'entrée dans un modèle simplifié de décharge. Les prédictions de la densité électronique, des changements de la température électronique et de l'impédance de la décharge coïncident bien avec les observations expérimentales. Notre modèle et nos observations expérimentales conduisent à une compréhension qualitative de l'effet optogalvanique dans une décharge de cathode creuse et à l'estimation de l'importance relative des deux mécanismes de l'effet optogalvanique.There are two significantly different mechanisms proposed for the origin of the optogalvanic effect in a hollow-cathode discharge. (1) Laser excitation of atoms to higher electronic states leads to an increased cross section for electron impact ionization, with the result that the excited atom becomes ionized and the conductivity of the discharge increases. (2) Laser excitation of atoms to higher electronic states perturbs the equilibrium established between the electron temperature and the atomic excitation temperature. Superelastic collisions between the electrons and the laser-excited atoms restore the equilibrium, with the excess energy ending up in an increased electron temperature and therefore an increase conductivity of the discharge. Both mechanisms undoubtedly proceed simultaneously and what needs to be determined is their relative importance at different discharge conditions and different excitation conditions. This is important because laser isotope enri chment schemes have been proposed using selective excitation in a hollow-cathode discharge. In order for these schemes to work, (1) must be the predominant mechanism. We have measured the optogalvanic signal, concentration of uranium atoms, impedance of the discharge, and electron temperature as a function of the discharge current in a neon-filled uranium hollow-cathode discharge. The hollow cathode operating characteristics are used as input parameters in a simple discharge model. Predictions of electron density, changes in electron temperature, and discharge impedance compare well with experimental observations. Our model and experimental observations yield a qualitative understanding of the optogalvanic effect in a hollow-cathode discharge and estimate the relative importance of the two optogalvanic mechanisms

Cholinergic interneurons in the nucleus accumbens regulate depression-like behavior

A large number of studies have demonstrated that the nucleus accumbens (NAC) is a critical site in the neuronal circuits controlling reward responses, motivation, and mood, but the neuronal cell type(s) underlying these processes are not yet known. Identification of the neuronal cell types that regulate depression-like states will guide us in understanding the biological basis of mood and its regulation by diseases like major depressive disorder. Taking advantage of recent findings demonstrating that the serotonin receptor chaperone, p11, is an important molecular regulator of depression-like states, here we identify cholinergic interneurons (CINs) as a primary site of action for p11 in the NAC. Depression-like behavior is observed in mice after decrease of p11 levels in NAC CINs. This phenotype is recapitulated by silencing neuronal transmission in these cells, demonstrating that accumbal cholinergic neuronal activity regulates depression-like behaviors and suggesting that accumbal CIN activity is crucial for the regulation of mood and motivation