Differing calcification processes in cultured vascular smooth muscle cells and osteoblasts

© 2019 Published by Elsevier Inc.Arterial medial calcification (AMC) is the deposition of calcium phosphate mineral, often as hydroxyapatite, inthe medial layer of the arteries. AMC shares some similarities to skeletal mineralisation and has been associatedwith the transdifferentiation of vascular smooth muscle cells (VSMCs) towards an osteoblast-like phenotype. Thisstudy used primary mouse VSMCs and calvarial osteoblasts to directly compare the established and widely usedin vitromodels of AMC and bone formation. Significant differences were identified between osteoblasts andcalcifying VSMCs. First, osteoblasts formed large mineralised bone nodules that were associated with widespreaddeposition of an extracellular collagenous matrix. In contrast, VSMCs formed small discrete regions of calcifi-cation that were not associated with collagen deposition and did not resemble bone. Second, calcifying VSMCsdisplayed a progressive reduction in cell viability over time (≤7-fold), with a 50% increase in apoptosis,whereas osteoblast and control VSMCs viability remained unchanged. Third, osteoblasts expressed high levels ofalkaline phosphatase (TNAP) activity and TNAP inhibition reduced bone formation by to 90%. TNAP activity incalcifying VSMCs was∼100-fold lower than that of bone-forming osteoblasts and cultures treated withβ-gly-cerophosphate, a TNAP substrate, did not calcify. Furthermore, TNAP inhibition had no effect on VSMC calci-fication. Although, VSMC calcification was associated with increased mRNA expression of osteoblast-relatedgenes (e.g. Runx2, osterix, osteocalcin, osteopontin), the relative expression of these genes was up to 40-foldlower in calcifying VSMCs versus bone-forming osteoblasts. In summary, calcifying VSMCsin vitrodisplay somelimited osteoblast-like characteristics but also differ in several key respects: 1) their inability to form collagen-containing bone; 2) their lack of reliance on TNAP to promote mineral deposition; and, 3) the deleterious effectof calcification on their viability.Peer reviewedFinal Published versio

Inequality in the household and rural-urban migration in Ethiopian farmers

International audienceAbstract Parental investment theory predicts that biases in investment favour migration by driving some of the sibling group to disperse for resources. Here we test hypotheses arising from this theory to explain patterns of rural–urban migration in south-central Ethiopia considering familial and individual strategies. We focus on the migration of low-skilled men, predicting two scenarios based on a low level of resource availability. Firstly, last-born sons will be more likely to migrate in order to offset their intra-household disadvantage when resources are limited (sibling competition). Alternatively, in households facing livelihood insecurity, older sons will migrate in order to free resources for their younger dependant brothers (reflecting sibling cooperation). Demographic, economic and relational data were collected from 217 families of male migrants, including information for 830 male adults. We performed multivariate analyses, including Bayesian generalised linear models and mixed models, to analyse quantitative data with a focus on household and individual likelihood of out-migration. Consistent with the predictions from parental investment theory, migration is dependent on intra-household resource allocation. Depending on the stage of the family cycle and livelihood context, families and individuals present different strategies: labour migration may result from sibling competition or from cooperation for resource enhancement.Abstrac

Randomized double-blind placebo-controlled trial of 40 mg/day of atorvastatin in reducing the severity of sepsis in ward patients (ASEPSIS Trial)

Introduction: Several observational studies suggest that statins modulate the pathophysiology of sepsis and may prevent its progression. The aim of this study was to determine if the acute administration of atorvastatin reduces sepsis progression in statin naïve patients hospitalized with sepsis. Methods: A single centre phase II randomized double-blind placebo-controlled trial. Patients with sepsis were randomized to atorvastatin 40 mg daily or placebo for the duration of their hospital stay up to a maximum of 28-days. The primary end-point was the rate of sepsis progressing to severe sepsis during hospitalization. Results: 100 patients were randomized, 49 to the treatment with atorvastatin and 51 to placebo. Patients in the atorvastatin group had a significantly lower conversion rate to severe sepsis compared to placebo (4% vs. 24% p = 0.007.), with a number needed to treat of 5. No significant difference in length of hospital stay, critical care unit admissions, 28-day and 12-month readmissions or mortality was observed. Plasma cholesterol and albumin creatinine ratios were significantly lower at day 4 in the atorvastatin group (p < 0.0001 and p = 0.049 respectively). No difference in adverse events between the two groups was observed (p = 0.238). Conclusions: Acute administration of atorvastatin in patients with sepsis may prevent sepsis progression. Further multi-centre trials are required to verify these findings. Trial Registration: International Standard Randomized Control Trial Registry ISRCTN64637517

Early intervention for stigma towards mental illness? Promoting positive attitudes towards severe mental illness in primary school children

Purpose Stigma towards severe mental illness (SMI) is widespread, exacerbating mental health problems, and impacting on help-seeking and social inclusion. Anti-stigma campaigns are meeting with success, but results are mixed. Earlier intervention to promote positive mental health literacy rather than challenge stigma, may show promise, but little is known about stigma development or interventions in younger children. This study will investigate (i) children’s knowledge, attitudes and behaviour towards SMI and (ii) whether we can positively influence children’s attitudes before stigma develops. Design/methodology/approach A cross sectional study investigated mental health schema in 7-11 year olds. An experimental intervention investigated whether an indirect contact story-based intervention in 7-8 year olds led to more positive mental health schema. Findings: Young children’s schema were initially positive, and influenced by knowledge and contact with mental illness & intergroup anxiety, but were more stigmatising in older girls as intergroup anxiety increased. The indirect contact intervention was effective in promoting positive mental health schema, partially mediated by knowledge. Social Implications: Intervening early to shape concepts of mental illness more positively, as they develop in young children, may represent a more effective strategy than attempting to challenge and change mental health stigma once it has formed in adolescents and adults. Originality/Value: This study is the first to investigate an intervention targeted at the prevention of stigma towards severe mental illness, in young children, at the point that stigma is emerging

Effect of Atmospheric cold Plasma on the Functional Properties of Whole Wheat (Triticum aestivum L.) Grain and Wheat Flour

Atmospheric cold plasma (ACP) has emerged as a novel processing technology, with demonstrated efficiencies in microbial inactivation. However, studies on the effects of ACP and potential to modify the functional properties of foods are sparse. The objective of this study is to determine the effect of ACP on physico-chemical and functional properties of wheat flour. In this study, both whole wheat grains and wheat flour were subjected to a dielectric barrier discharge (DBD) contained plasma reactor for a range of treatment times (5–30 min) at 80 kV. Plasma treatment increased the flour hydration properties of wheat flour. Rapid visco-analyser results showed an increase in pasting and the final viscosities of wheat flour. The decrease in both endothermic enthalpies and crystallinity was attributed to the depolymerization of starch and plasma-induced changes. Overall DBD-ACP treatment can be tailored to develop a plasma process with potential to improve functionality of wheat flour

Awareness of product-related information, health messages and warnings on alcohol packaging among adolescents: A cross-sectional survey in the United Kingdom

Background: Alcohol packaging can be used to communicate product-related information, health messages, and health warnings to consumers. We examined awareness and recall of such information and messaging among adolescents in the United Kingdom. Method: A cross-sectional survey was conducted with 11-19 year olds in the United Kingdom (n=3,399), with participants asked if they had seen any information, health messages or warnings on alcohol packaging in the past month (Yes/No) and, if so, what they recalled. We also assessed higher-risk drinking among current drinkers (>5 Alcohol Use Disorders Identification Test-Consumption) and susceptibility to consume among never-drinkers. Results: One-third (32%) of participants had seen information, health messages or warnings on alcohol packaging. Chi-Square tests showed awareness was greater for current drinkers than never-drinkers (46% vs. 19%; p < 0.001), higher-risk drinkers than lower-risk drinkers (55% vs. 39%; P < 0.001), and susceptible never-drinkers than non-susceptible never-drinkers (21% vs. 16%; P = 0.01). Ten messages were recalled, with drinking responsibly (18%) and not drinking during pregnancy (13%) most recalled. Conclusion Most young drinkers, including almost half of higher-risk drinkers, did not recall seeing any information, health messages or warnings on alcohol packaging in the past month, suggesting that current labelling is failing to reach this key audience

Prostanoid receptors in GtoPdb v.2023.1

Prostanoid receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Prostanoid Receptors [701]) are activated by the endogenous ligands prostaglandins PGD2, PGE1, PGE2 , PGF2α, PGH2, prostacyclin [PGI2] and thromboxane A2. Differences and similarities between human and rodent prostanoid receptor orthologues, and their specific roles in pathophysiologic conditions are reviewed in [452]. Measurement of the potency of PGI2 and thromboxane A2 is hampered by their instability in physiological salt solution; they are often replaced by cicaprost and U46619, respectively, in receptor characterization studies

Inhibition of vascular smooth muscle cell calcification by ATP analogues

Arterial medial calcification (AMC) has been associated with phenotypic changes in vascular smooth muscle cells (VSMCs) that reportedly makes them more osteoblast-like. Previous work has shown that ATP/UTP can inhibit AMC directly via P2 receptors and indirectly by NPP1-mediated hydrolysis to produce the mineralisation inhibitor, pyrophosphate (PPi). This study investigated the role of P2X receptors in the inhibitory effects of extracellular nucleotides on VSMC calcification. We found that Bz-ATP, α,β-meATP and β,γ-meATP, inhibited calcification by up to 100%. Culture in a high phosphate medium (2mM) was associated with increased VSMC death and apoptosis; treatment with Bz-ATP, α,β-meATP and β,γ-meATP reduced apoptosis to levels seen in non-calcifying cells. Calcification was also associated with alterations in the protein levels of VSMC (e.g. SM22α, SMA) and osteoblast-associated (e.g. Runx2, osteopontin) markers; Bz-ATP, α,β-meATP and β,γ-meATP attenuated these changes in protein expression. Long-term culture with Bz-ATP, α,β-meATP and β,γ-meATP resulted in lower extracellular ATP levels and an increased rate of ATP breakdown. P2X receptor antagonists failed to prevent the inhibitory effects of these analogues suggesting that they act via P2X receptor-independent mechanisms. In agreement, the breakdown products of α,β-meATP and β,γ-meATP (α,β-meADP and methylene diphosphonate, respectively) also dose dependently inhibited VSMC calcification. Furthermore, the actions of Bz-ATP, α,β-meATP and β,γ-meATP were unchanged in VSMCs isolated from NPP1 knockout mice, suggesting that the functional effects of these compounds do not involve NPP1-mediated generation of PPi. Together, these results indicate that the inhibitory effects of ATP analogues on VSMC calcification and apoptosis in vitro may be mediated, at least in part, by mechanisms that are independent of purinergic signalling and PPi

Prostanoid receptors in GtoPdb v.2023.1

Prostanoid receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Prostanoid Receptors [701]) are activated by the endogenous ligands prostaglandins PGD2, PGE1, PGE2 , PGF2&#945;, PGH2, prostacyclin [PGI2] and thromboxane A2. Differences and similarities between human and rodent prostanoid receptor orthologues, and their specific roles in pathophysiologic conditions are reviewed in [452]. Measurement of the potency of PGI2 and thromboxane A2 is hampered by their instability in physiological salt solution; they are often replaced by cicaprost and U46619, respectively, in receptor characterization studies