2-Arachidonoylglycerol mobilizes myeloid cells and worsens heart function after acute myocardial infarction.

Myocardial infarction (MI) leads to an enhanced release of endocannabinoids and a massive accumulation of neutrophils and monocytes within the ischaemic myocardium. These myeloid cells originate from haematopoietic precursors in the bone marrow and are rapidly mobilized in response to MI. We aimed to determine whether endocannabinoid signalling is involved in myeloid cell mobilization and cardiac recruitment after ischaemia onset. Intravenous administration of endocannabinoid 2-arachidonoylglycerol (2-AG) into wild type (WT) C57BL6 mice induced a rapid increase of blood neutrophil and monocyte counts as measured by flow cytometry. This effect was blunted when using cannabinoid receptor 2 knockout mice. In response to MI induced in WT mice, the lipidomic analysis revealed significantly elevated plasma and cardiac levels of the endocannabinoid 2-AG 24 h after infarction, but no changes in anandamide, palmitoylethanolamide, and oleoylethanolamide. This was a consequence of an increased expression of 2-AG synthesizing enzyme diacylglycerol lipase and a decrease of metabolizing enzyme monoacylglycerol lipase (MAGL) in infarcted hearts, as determined by quantitative RT-PCR analysis. The opposite mRNA expression pattern was observed in bone marrow. Pharmacological blockade of MAGL with JZL184 and thus increased systemic 2-AG levels in WT mice subjected to MI resulted in elevated cardiac CXCL1, CXCL2, and MMP9 protein levels as well as higher cardiac neutrophil and monocyte counts 24 h after infarction compared with vehicle-treated mice. Increased post-MI inflammation in these mice led to an increased infarct size, an impaired ventricular scar formation assessed by histology and a worsened cardiac function in echocardiography evaluations up to 21 days. Likewise, JZL184-administration in a myocardial ischaemia-reperfusion model increased cardiac myeloid cell recruitment and resulted in a larger fibrotic scar size. These findings suggest that changes in endocannabinoid gradients due to altered tissue levels contribute to myeloid cell recruitment from the bone marrow to the infarcted heart, with crucial consequences on cardiac healing and function

Driven Topological Transitions in Active Nematic Films

The topological properties of many materials are central to their behavior, with the dynamics of topological defects being particularly important to intrinsically out-of-equilibrium, active materials. In this paper, local manipulation of the ordering, dynamics, and topological properties of microtubule-based extensile active nematic films is demonstrated in a joint experimental and simulation study. Hydrodynamic stresses created by magnetically actuated rotation of disk-shaped colloids in proximity to the films compete with internal stresses in the active nematic, enabling local control of the motion of the +1/2 charge topological defects that are intrinsic to spontaneously turbulent active films. Sufficiently large applied stresses drive the formation of +1 charge topological vortices in the director field through the merger of two +1/2 defects. The directed motion of the defects is accompanied by ordering of the vorticity and velocity of the active flows within the film that is qualitatively unlike the response of passive viscous films. Many features of the film's response to the disk are captured by Lattice Boltzmann simulations, leading to insight into the anomalous viscoelastic nature of the active nematic. The topological vortex formation is accompanied by a rheological instability in the film that leads to significant increase in the flow velocities. Comparison of the velocity profile in vicinity of the vortex with fluid-dynamics calculations provides an estimate of film viscosity

Coping strategies and postpartum depressive symptoms: A structural equation modelling approach

BACKGROUND: Variables such as the mother's personality, social support, coping strategies and stressful events have been described as risk factors for postpartum depression. Structural Equation Modelling (SEM) analysis was used to examine whether neuroticism, perceived social support, perceived life events, and coping strategies are associated with postpartum depressive symptoms at the 8th and 32nd weeks. METHODS: A total of 1626 pregnant women participated in a longitudinal study. Different evaluations were performed 8 and 32weeks after delivery. Several measures were used: the Edinburgh Postnatal Depression Scale (EPDS), the Diagnostic Interview for Genetic Studies (DIGS), the Eysenck Personality Questionnaire (EPQ-RS), the St. Paul Ramsey life events scale and the Duke-UNC Functional Social Support Questionnaire. The brief COPE scale was used to measure coping strategies. SEM analysis was conducted for all women and in those women with a clinical diagnosis of postpartum depression. RESULTS: Passive coping strategies were associated with postpartum depressive symptoms at both visits (8th and 32nd weeks). Neuroticism was associated with more passive coping strategies and less active coping strategies. Neuroticism and life stress were positively correlated, and social support was negatively correlated with life stress and neuroticism. CONCLUSIONS: Early identification of potential risk for symptomatology of depression postpartum should include assessment of neuroticism, life events, social support and coping strategies.Gobierno de España. Instituto de Salud Carlos III (ISCIII)Spanish Psychiatric Genetics and Genotyping networkRTAGeneralitat de Cataluny

Research Letter: Is neuroticism a risk factor for postpartum depression?

Although the relationship between personality and depressive illness is complex (Shea, 2005), there is empirical evidence that some personality features such as neuroticism, harm avoidance, introversion, dependency, self-criticism or perfectionism are related to depressive illness risk (Gunderson et al. 1999).This work was supported by the Instituto Carlos III (Spanish Ministry of Health; grant numbers P1041635, PI041783, PI041779, PI0411761, PI041791, PI041766 and PI041782), as well as the Spanish Psychiatric Genetics and Genotyping network G03/184, RTA (RD06/001/1009), and Generalitat de Catalunya, SGR2009/1435).Ye

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Endocannabinoid signalling in atherosclerosis and related metabolic complications.

Endocannabinoids are a group of arachidonic acid-derived lipid mediators binding to cannabinoid receptors CB1 and CB2. An overactivity of the endocannabinoid system plays a pathophysiological role in the development of visceral obesity and insulin resistance. Moreover, elevated circulating endocannabinoid levels are also prevalent in atherosclerosis. The pathophysiological increase of endocannabinoid levels is due to an altered expression of endocannabinoid synthesizing and degrading enzymes induced by inflammatory mediators such as cytokines or lipids. Emerging experimental evidence suggests that enhanced endocannabinoid signalling affects atherosclerosis via multiple effects, including a modulation of vascular inflammation, leukocyte recruitment, macrophage cholesterol metabolism and consequently atherosclerotic plaque stability. In addition, recent findings in various metabolic disease models highlight the relevance of peripheral CB1 cannabinoid receptors in adipose tissue, liver and pancreas, which crucially regulate lipid and glucose metabolism as well as macrophage properties in these organs. This suggests that targeting the endocannabinoid system in the vasculature and peripheral organs might have a therapeutic potential for atherosclerosis by inhibiting vascular inflammation and improving metabolic risk factors. This review will provide a brief update on the effects of endocannabinoid signalling in atherosclerosis and related metabolic complications