423 research outputs found

    An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors

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    Sodium-glucose co-transporter 2 (SGLT2) inhibitors block glucose reabsorption in the renal proximal tubule, an insulin-independent mechanism that plays a critical role in glycemic regulation in diabetes. In addition to their glucose-lowering effects, SGLT2 inhibitors prevent both renal damage and the onset of chronic kidney disease and cardiovascular events, in particular heart failure with both reduced and preserved ejection fraction. These unexpected benefits prompted changes in treatment guidelines and scientific interest in the underlying mechanisms. Aside from the target effects of SGLT2 inhibition, a wide spectrum of beneficial actions is described for the kidney and the heart, even though the cardiac tissue does not express SGLT2 channels. Correction of cardiorenal risk factors, metabolic adjustments ameliorating myocardial substrate utilization, and optimization of ventricular loading conditions through effects on diuresis, natriuresis, and vascular function appear to be the main underlying mechanisms for the observed cardiorenal protection. Additional clinical advantages associated with using SGLT2 inhibitors are antifibrotic effects due to correction of inflammation and oxidative stress, modulation of mitochondrial function, and autophagy. Much research is required to understand the numerous and complex pathways involved in SGLT2 inhibition. This review summarizes the current known mechanisms of SGLT2-mediated cardiorenal protection

    GIADA: shining a light on the monitoring of the comet dust production from the nucleus of 67P/Churyumov Gerasimenko

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    Context. During the period between 15 September 2014 and 4 February 2015, the Rosetta spacecraft accomplished the circular orbit phase around the nucleus of comet 67P/Churyumov-Gerasimenko (67P). The Grain Impact Analyzer and Dust Accumulator (GIADA) onboard Rosetta monitored the 67P coma dust environment for the entire period. Aims. We aim to describe the dust spatial distribution in the coma of comet 67P by means of in situ measurements. We determine dynamical and physical properties of cometary dust particles to support the study of the production process and dust environment modification. Methods. We analyzed GIADA data with respect to the observation geometry and heliocentric distance to describe the coma dust spatial distribution of 67P, to monitor its activity, and to retrieve information on active areas present on its nucleus. We combined GIADA detection information with calibration activity to distinguish different types of particles that populate the coma of 67P: compact particles and fluffy porous aggregates. By means of particle dynamical parameters measured by GIADA, we studied the dust acceleration region. Results. GIADA was able to distinguish different types of particles populating the coma of 67P: compact particles and fluffy porous aggregates. Most of the compact particle detections occurred at latitudes and longitudes where the spacecraft was in view of the comet’s neck region of the nucleus, the so-called Hapi region. This resulted in an oscillation of the compact particle abundance with respect to the spacecraft position and a global increase as the comet moved from 3.36 to 2.43 AU heliocentric distance. The speed of these particles, having masses from 10-10 to 10-7 kg, ranged from 0.3 to 12.2 m s−1. The variation of particle mass and speed distribution with respect to the distance from the nucleus gave indications of the dust acceleration region. The influence of solar radiation pressure on micron and submicron particles was studied. The integrated dust mass flux collected from the Sun direction, that is, particles reflected by solar radiation pressure, was three times higher than the flux coming directly from the comet nucleus. The awakening 67P comet shows a strong dust flux anisotropy, confirming what was suggested by on-ground dust coma observations performed in 2008

    Comet 67P/Churyumov-Gerasimenko preserved the pebbles that formed planetesimals

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    Solar System formation models predict that the building-blocks of planetesimals were mm- to cm-sized pebbles, aggregates of ices and non-volatile materials, consistent with the compact particles ejected by comet 67P/Churyumov-Gerasimenko (67P hereafter) and detected by GIADA (Grain Impact Analyzer and Dust Accumulator) on-board the Rosetta spacecraft. Planetesimals were formed by the gentle gravitational accretion of pebbles, so that they have an internal macroporosity of 40%. We measure the average dust bulk density ρD=79565+840kgm3{\rho}D = 795 _{-65}^{+840} kg m^{-3} that, coupled to the 67P nucleus bulk density, provides the average dust-to-ices mass ratio δ = 8.5. We find that the measured densities of the 67P pebbles are consistent with a mixture of (15 ± 6)% of ices, (5 ± 2)% of Fe-sulfides, (28 ± 5)% of silicates, and (52 ± 12)% of hydrocarbons, in average volume abundances. This composition matches both the solar and CI-chondritic chemical abundances, thus showing that GIADA has sampled the typical non-volatile composition of the pebbles that formed all planetesimals. The GIADA data do not constrain the abundance of amorphous silicates vs. crystalline Mg,Fe- olivines and pyroxenes. We find that the pebbles have a microporosity of (52 ± 8)% (internal volume filling factor φP = 0.48±0.08), implying an average porosity for the 67P nucleus of (71 ± 8)%, lower than previously estimated

    GIADA: its status after the Rosetta cruise phase and on-ground activity in support of the encounter with comet 67P/Churyumov-Gerasimenko

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    GIADA (Grain Impact Analyser and Dust Accumulator) on-board the Rosetta mission to comet 67P/Churyumov-Gerasimenko was designed to study the physical and dynamical properties of dust particles ejected by the comet during the encounter. In this paper we report the results of the analysis of data collected by GIADA during the past seven years of the cruise phase. During this period the GIADA detection subsystems were switched on for periodic in-flight payload checkouts to monitor their state of-health including potential changes in its performance that could affect its data collection. Only slight variations in sensitivity and dynamical range were identified that will not affect the GIADA measurement capability during the Rosetta comet encounter and rendezvous phase. The GIADA microbalance system detected the presence of low-volatility material over a period of about 169 days when the GIADA cover remained partially opened. It is highly probable that this material originated from the spacecraft itself, as a spacecraft’s outgassing was observed by the ROSINA mass spectrometer (on-board Rosetta) during the cruise phase. The identification of the low-volatility mass deposited on the microbalances as self-contamination will allow us to evaluate the mass rate background to be subtracted from the GIADA science data. These results obtained from GIADA cruise data analysis coupled with laboratory calibration data obtained from measurements using the GIADA spare model for selected cometary dust analogs will be the basis for the interpretation of the GIADA scientific data

    Survival and Recurrence of Endocarditis following Mechanical vs. Biological Aortic Valve Replacement for Endocarditis in Patients Aged 40 to 65 Years: Data from the INFECT-Registry

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    Background: Infective endocarditis (IE) is a serious disease, and in many cases, surgery is necessary. Whether the type of prosthesis implanted for aortic valve replacement (AVR) for IE impacts patient survival is a matter of debate. The aim of the present study is to quantify differences in long-term survival and recurrence of endocarditis AVR for IE according to prosthesis type among patients aged 40 to 65 years. Methods: This was an analysis of the INFECT-REGISTRY. Trends in proportion to the use of mechanical prostheses versus biological ones over time were tested by applying the sieve bootstrapped t-test. Confounders were adjusted using the optimal full-matching propensity score. The difference in overall survival was compared using the Cox model, whereas the differences in recurrence of endocarditis were evaluated using the Gray test. Results: Overall, 4365 patients were diagnosed and operated on for IE from 2000 to 2021. Of these, 549, aged between 40 and 65 years, underwent AVR. A total of 268 (48.8%) received mechanical prostheses, and 281 (51.2%) received biological ones. A significant trend in the reduction of implantation of mechanical vs. biological prostheses was observed during the study period (p < 0.0001). Long-term survival was significantly higher among patients receiving a mechanical prosthesis than those receiving a biological prosthesis (hazard ratio [HR] 0.546, 95% CI: 0.322–0.926, p = 0.025). Mechanical prostheses were associated with significantly less recurrent endocarditis after AVR than biological prostheses (HR 0.268, 95%CI: 0.077–0.933, p = 0.039). Conclusions: The present analysis of the INFECT-REGISTRY shows increased survival and reduced recurrence of endocarditis after a mechanical aortic valve prosthesis implant for IE in middle-aged patients

    Density and Charge of Pristine Fluffy Particles from Comet 67P/Churyumov–Gerasimenko

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    The Grain Impact Analyzer and Dust Accumulator (GIADA) instrument on board ESA’s Rosetta mission is constraining the origin of the dust particles detected within the coma of comet 67 P/Churyumov–Gerasimenko (67P). The collected particles belong to two families: (i) compact particles (ranging in size from 0.03 to 1 mm), witnessing the presence of materials that underwent processing within the solar nebula and (ii) fluffy aggregates (ranging in size from 0.2 to 2.5 mm) of sub-micron grains that may be a record of a primitive component, probably linked to interstellar dust. The dynamics of the fluffy aggregates constrain their equivalent bulk density to -3. These aggregates are charged, fragmented, and decelerated by the spacecraft negative potential and enter GIADA in showers of fragments at speeds -1. The density of such optically thick aggregates is consistent with the low bulk density of the nucleus. The mass contribution of the fluffy aggregates to the refractory component of the nucleus is negligible and their coma brightness contribution is less than 15%
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