Procalcific Phenotypic Drift of Circulating Progenitor Cells in Type 2 Diabetes with Coronary Artery Disease

Diabetes mellitus (DM) alters circulating progenitor cells relevant for the pathophysiology of coronary artery disease (CAD). While endothelial progenitor cells (EPCs) are reduced, there is no data on procalcific polarization of circulating progenitors, which may contribute to vascular calcification in these patients. In a cohort of 107 subjects with and without DM and CAD, we analyzed the pro-calcific versus endothelial differentiation status of circulating CD34+ progenitor cells. Endothelial commitment was determined by expression of VEGFR-2 (KDR) and pro-calcific polarization by expression of osteocalcin (OC) and bone alkaline phosphatase (BAP). We found that DM patients had significantly higher expression of OC and BAP on circulating CD34+ cells than control subjects, especially in the presence of CAD. In patients with DM and CAD, the ratio of OC/KDR, BAP/KDR, and OC+BAP/KDR was about 3-fold increased than in other groups. EPCs cultured from DM patients with CAD occasionally formed structures highly suggestive of calcified nodules, and the expression of osteogenic markers by EPCs from control subjects was significantly increased in response to the toll-like receptor agonist LPS. In conclusion, circulating progenitor cells of diabetic patients show a phenotypic drift toward a pro-calcific phenotype that may be driven by inflammatory signals

The Oral Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Increases Circulating Endothelial Progenitor Cells in Patients With Type 2 Diabetes: Possible role of stromal-derived factor-1α

OBJECTIVE: Vasculoprotective endothelial progenitor cells (EPCs) are regulated by stromal-derived factor-1alpha (SDF-1alpha) and are reduced in type 2 diabetes. Because SDF-1alpha is a substrate of dipeptidyl-peptidase-4 (DPP-4), we investigated whether the DPP-4 inhibitor sitagliptin modulates EPC levels in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: This was a controlled, nonrandomized clinical trial comparing 4-week sitagliptin (n = 16) versus no additional treatment (n = 16) in addition to metformin and/or secretagogues in type 2 diabetic patients. We determined circulating EPC levels and plasma concentrations of SDF-1alpha, monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and nitrites/nitrates. RESULTS: There was no difference in clinical baseline data between the sitagliptin and control arms. After 4 weeks, as compared with control subjects, patients receiving sitagliptin showed a significant increase in EPCs and SDF-1alpha and a decrease in MCP-1. CONCLUSIONS: Sitagliptin increases circulating EPCs in type 2 diabetic patients with concomitant upregulation of SDF-1alpha. This ancillary effect of DPP-4 inhibition might have potential favorable cardiovascular implications

Effects of androgens on endothelial progenitor cells in vitro and in vivo

The beneficial or detrimental effects of androgens on the cardiovascular system are debated. Endothelial progenitor cells are bone-marrow-derived cells involved in endothelial healing and angiogenesis, which promote cardiovascular health. Oestrogens are potent stimulators of endothelial progenitor cells, and previous findings have indicated that androgens may improve the biology of these cells as well. In the present study, we show that testosterone and its active metabolite dihydrotestosterone exert no effects on the expansion and function of late endothelial progenitors isolated from the peripheral blood of healthy human adult males, whereas they positively modulate early ‘monocytic’ endothelial progenitor cells. In parallel, we show that castration in rats is followed by a decrease in circulating endothelial progenitor cells, but that testosterone and dihydrotestosterone replacement fails to restore endothelial progenitor cells towards normal levels. This is associated with persistently low oestrogen levels after androgen replacement in castrated rats. In a sample of 62 healthy middle-aged men, we show that circulating endothelial progenitor cell levels are more directly associated with oestradiol, rather than with testosterone, concentrations. In conclusion, our results collectively demonstrate that androgens exert no direct effects on endothelial progenitor cell biology in vitro and in vivo

Inflation, fiscal policy and inequality: the distributional impact of fiscal measures to compensate for consumer inflation

En este documento se analiza el impacto distributivo de la elevada inflación experimentada por los consumidores en la eurozona y las medidas que los Gobiernos han implementado para compensar a los hogares en 2022. El estudio utiliza el modelo de microsimulación de impuestos y beneficios para la Unión Europea (EUROMOD) basado en microdatos —estadísticas de la Unión Europea sobre la renta y las condiciones de vida (EU-SILC) y encuestas de presupuestos familiares (HBS)— para cuantificar el impacto distributivo de la inflación, de las medidas de apoyo a la renta de los hogares y de las medidas destinadas a contener los precios. El análisis confirma que el poder adquisitivo y la métrica de bienestar se vieron más gravemente afectados por el aumento de la inflación de 2022 en los hogares de menores ingresos que en los hogares de mayores ingresos. Las medidas fiscales compensaron a los hogares en alrededor de un tercio de su pérdida de bienestar, aunque con diferencias significativas entre países. Al mismo tiempo, las medidas fiscales cerraron alrededor del 60 % de la brecha de desigualdad que había entre los hogares de menores ingresos y los de mayores ingresos. La mayoría de las medidas fiscales no estaban bien focalizadas en los hogares de bajos ingresos, lo que dio lugar a un coste fiscal superior al necesario para amortiguar el impacto distributivo del shock inflacionario.This paper analyses the distributional impact of high consumer inflation in the euro area and government measures to compensate households in 2022. The study uses the tax-benefit microsimulation model for the European Union (EUROMOD) with microdata as the input – EU statistics on income and living conditions (EU-SILC) and household budget surveys (HBS) – to quantify the distributional impact of inflation, income support measures and measures aimed at containing prices. The analysis confirms that purchasing power and welfare were more severely affected by the 2022 inflation surge among lower-income households than among higher-income households. Fiscal measures compensated households for about a third of their welfare loss, though with significant differences across countries. At the same time, fiscal measures reduced the inequality gap between lower and higher-income households by around 60%. Most fiscal measures were not particularly well targeted at low-income households, resulting in a higher than necessary fiscal burden to cushion the distributional impact of the inflationary shock

Overview on electrical issues faced during the SPIDER experimental campaigns

SPIDER is the full-scale prototype of the ion source of the ITER Heating Neutral Beam Injector, where negative ions of Hydrogen or Deuterium are produced by a RF generated plasma and accelerated with a set of grids up to ~100 keV. The Power Supply System is composed of high voltage dc power supplies capable of handling frequent grid breakdowns, high current dc generators for the magnetic filter field and RF generators for the plasma generation. During the first 3 years of SPIDER operation different electrical issues were discovered, understood and addressed thanks to deep analyses of the experimental results supported by modelling activities. The paper gives an overview on the observed phenomena and relevant analyses to understand them, on the effectiveness of the short-term modifications provided to SPIDER to face the encountered issues and on the design principle of long-term solutions to be introduced during the currently ongoing long shutdown.Comment: 8 pages, 12 figures. Presented at SOFT 202

Causes of unrest at silicic calderas in the East African Rift: new constraints from InSAR and soil-gas chemistry at Aluto volcano, Ethiopia

This work is a contribution to the Natural Environment Research Council (NERC) funded RiftVolc project (NE/L013932/1, Rift volcanism: past, present, and future). W.H., J.B., T.A.M., and D.M.P. are supported by and contribute to the NERC Centre for the Observation and Modelling of Earthquakes, Volcanoes, and Tectonics (COMET). Envisat data were provided by ESA. ALOS data were provided through ESA third party mission. W.H. funded by NERC studentship, NE/J5000045/1. Additional funding for fieldwork was provided by University College (University of Oxford), the Geological Remote Sensing Group, the Edinburgh Geological Society, and the Leverhulme Trust. Analytical work at the University of New Mexico was supported by the Volcanic and Geothermal Volatiles Lab at the Center for Stable Isotopes and an NSF grant EAR-1113066 to T.P.F.Restless silicic calderas present major geological hazards, and yet many also host significant untapped geothermal resources. In East Africa this poses a major challenge, although the calderas are largely unmonitored their geothermal resources could provide substantial economic benefits to the region. Understanding what causes unrest at these volcanoes is vital for weighing up the opportunities against the potential risks. Here we bring together new field and remote sensing observations to evaluate causes of ground deformation at Aluto, a restless silicic volcano located in the Main Ethiopian Rift (MER). Interferometric Synthetic Aperture Radar (InSAR) data reveal the temporal and spatial characteristics of a ground deformation episode that took place between 2008 and 2010. Deformation time-series reveal pulses of accelerating uplift that transition to gradual long-term subsidence, and analytical models support inflation source depths of ∼5 km. Gases escaping along the major fault zone of Aluto show high CO2 flux, and a clear magmatic carbon signature (CO2–δ13C of −4.2 to −4.5 ‰). This provides compelling evidence that the magmatic and hydrothermal reservoirs of the complex are physically connected. We suggest that a coupled magmatic-hydrothermal system can explain the uplift-subsidence signals. We hypothesize that magmatic fluid injection and/or intrusion in the cap of the magmatic reservoir drives edifice wide inflation while subsequent deflation is related to magmatic degassing and depressurization of the hydrothermal system. These new constraints on the plumbing of Aluto yield important insights into the behaviour of rift volcanic systems and will be crucial for interpreting future patterns of unrest.Publisher PDFPeer reviewe

B-Corp and benefit corporations: descriptive statistical analysis of B-Corp

openLo studio nella prima parte si interessa del movimento B-Corp e delle benefit corporation. In particolare presenta argomenti come lo strumento di valutazione Benefit Impact Assessment, utilizzato dall’ente B Lab per certificare le imprese B-Corp, le motivazioni che spingono un’azienda a certificarsi e le tensioni che nascono per conciliare aspetti economici e sostenibili. Affronta poi il tema inerente ai business model e nello specifico approfondisce i modelli utilizzati dalle imprese per raggiungere obiettivi sostenibili. La seconda parte sarà composta da una ricerca che ha l’obiettivo di fornire un’analisi statistico-descrittiva delle B-Corp, evidenziando le differenze che possono nascere a seconda del Paese, del settore e della dimensione dell’impresa stessa

Longitudinal assessment of the effect of cannabis use on hospital readmission rates in early psychosis:A 6-year follow-up in an inpatient cohort

Cannabis is the most commonly used illicit drug in psychosis patients and has been identified as a risk factor for relapse and subsequent hospital readmission, having substantial economic implications. To clarify the contribution of cannabis consumption to hospital readmission, a consecutive inpatient cohort of 161 early psychosis patients was included into the study. Data on cannabis use at admission and number of hospital readmissions and length of stay (LOS, number of inpatient days) in a 6-year follow-up was extracted from clinical notes. 62.4% of the patients had lifetime cannabis use. Their admission lasted on average 54.3 +/- 75 days and over the following 6 years patients had 2.2 +/- 2.8 hospital readmissions, for a total of 197.4 +/- 331.5 days. Cannabis use significantly predicted the number of hospital readmissions and LOS in the following 6 years, the latter remaining significant after adjusting for use of other substance. Cannabis-using patients of male gender and Black ethnicity had a longer LOS at follow-up compared to female patients and other ethnic groups, respectively. Having a history of cannabis use when admitted to an early intervention inpatient unit for psychosis is associated with a higher number of subsequent hospital readmissions and a longer LOS, especially in male and Black patients