Summary
Background
Gut microbiota modifiers may have beneficial effects of non‐alcoholic fatty liver disease (NAFLD) but randomised controlled trials (RCT) are lacking in children.
Aim
To perform a ...double‐blind RCT of VSL#3 vs. placebo in obese children with biopsy‐proven NAFLD.
Methods
Of 48 randomised children, 44 (22 VSL#3 and 22 placebo) completed the study. The main outcome was the change in fatty liver severity at 4 months as detected by ultrasonography. Secondary outcomes were the changes in triglycerides, insulin resistance as detected by the homoeostasis model assessment (HOMA), alanine transaminase (ALT), body mass index (BMI), glucagon‐like peptide 1 (GLP‐1) and activated GLP‐1 (aGLP‐1). Ordinal and linear models with cluster confidence intervals were used to evaluate the efficacy of VSL#3 vs. placebo at 4 months.
Results
At baseline, moderate and severe NAFLD were present in 64% and 36% of PLA children and in 55% and 45% of VSL#3 children. The probability that children supplemented with VSL#3 had none, light, moderate or severe FL at the end of the study was 21%, 70%, 9% and 0% respectively with corresponding values of 0%, 7%, 76% and 17% for the placebo group (P < 0.001). No between‐group differences were detected in triglycerides, HOMA and ALT while BMI decreased and GLP‐1 and aGLP1 increased in the VSL#3 group (P < 0.001 for all comparisons).
Conclusions
A 4‐month supplement of VSL#3 significantly improves NAFLD in children. The VSL#3‐dependent GLP‐1 increase could be responsible for these beneficial effects. Trial identifier: NCT01650025 (www.clinicaltrial.gov)
Summary
Background
Circulating microRNAs (miRNAs) may act as biomarkers of metabolic disturbances.
Objective
The aim of this study was to identify serum miRNAs signature of early insulin resistance ...in obese preschoolers.
Methods
Twelve obese children, aged 2–6 years, six insulin resistant (IR) and six controls were selected being age‐matched, sex‐matched and body mass index‐matched. Profiling of 179 circulating miRNAs, known to be widely expressed in the bloodstream, was investigated by quantitative polymerase chain reaction at fasting and 120 min following a standard oral glucose tolerance test (OGTT).
Results
Twenty‐one miRNAs were differentially regulated in IR obese preschoolers. miR‐200c‐3p, miR‐190a and miR‐95 were differently regulated both at fasting and 120 min after the OGTT. In controls, the fold changes of some miRNAs were correlated with Δglucose0‐120 (miR‐660, miR‐26b‐5p and miR‐22‐3p: p = 0.005 for all) and Δinsulin0‐120 (miR‐660 and miR‐22‐3p: p = 0.02 for both and miR‐423‐5p: p = 0.042). In IR patients, miR‐1 fold changes were correlated with Δglucose0‐120 (r = −0.786; p = 0.036) and Δinsulin0‐120 (r = −0.821; p = 0.023).
Conclusions
Our study identifies circulating miR‐200c‐3p, miR‐190a and miR‐95 as biomarkers of insulin resistance in obese preschoolers, being differentially regulated in IR patients both in fasting condition and after the OGTT. Expression of some circulating miRNAs seems reflecting glucose and insulin excursion following the OGTT differently in controls and IR obese preschoolers.
Discovering the nature of Dark Matter (DM) is one of the fundamental challenges of the modern physics. Indirect searches of DM are devoted to look for non-gravitational signals of its presence in the ...highly DM dominated cosmic regions. Within the weakly interacting massive particles (WIMPs) scenario, we expect very high energy (VHE) gamma-ray emissions resulting from annihilation and/or decay of DM particles. Since the beginning of operations, the Major Atmospheric Gamma Imaging Cherenkov (MAGIC) telescopes are carrying out deep observations of several promising DM targets, with the aim of detecting such signals or alternatively setting stringent constrains to DM particle models in the TeV mass region. In this contribution we present the latest indirect DM search results achieved by MAGIC on several targets, such as dwarf satellites - where MAGIC reached the strongest constraints on DM annihilation searches above few hundreds of GeV -, galaxy clusters, and the Galactic Center.
The nature of Dark Matter (DM) is an open issue of modern physics. Cosmological considerations and observational evidences indicate a behaviour beyond the Standard Model for feasible DM particle ...candidates. Non-baryonic DM is compatible with cold and weakly interacting massive particles (WIMPs) expected to have a mass in the range between ∼10 GeV and ∼100 TeV. Indirect DM searches with imaging atmospheric Cherenkov telescopes may play a crucial role in constraining the nature of the DM particle(s) through the study of their annihilation in very high energy (VHE) gamma rays from promising targets, such as the dwarf spheroidal satellite galaxies (dSphs) of the Milky Way. Here, we focus on indirect DM searches in dSphs, presenting the preliminary prospects of this research beyond the TeV mass region achievable with the ASTRI mini-array, proposed to be installed at the Cherenkov Telescope Array southern site.
Abstract
It is widely believed that the bulk of the Galactic cosmic rays is accelerated in supernova remnants (SNRs). However, no observational evidence of the presence of particles of PeV energies ...in SNRs has yet been found. The young historical SNR Cassiopeia A (Cas A) appears as one of the best candidates to study acceleration processes. Between 2014 December and 2016 October, we observed Cas A with the MAGIC telescopes, accumulating 158 h of good quality data. We derived the spectrum of the source from 100 GeV to 10 TeV. We also analysed ∼8 yr of Fermi-LAT to obtain the spectral shape between 60 MeV and 500 GeV. The spectra measured by the LAT and MAGIC telescopes are compatible within the errors and show a clear turn-off (4.6σ) at the highest energies, which can be described with an exponential cut-off at
$E_c = 3.5(^{+1.6}_{-1.0})_{{\rm stat}} (^{+0.8}_{-0.9})_{{\rm sys}}$
TeV. The gamma-ray emission from 60 MeV to 10 TeV can be attributed to a population of high-energy protons with a spectral index of ∼2.2 and an energy cut-off at ∼10 TeV. This result indicates that Cas A is not contributing to the high energy (∼PeV) cosmic ray sea in a significant manner at the present moment. A one-zone leptonic model fails to reproduce by itself the multiwavelength spectral energy distribution. Besides, if a non-negligible fraction of the flux seen by MAGIC is produced by leptons, the radiation should be emitted in a region with a low magnetic field (B⪅180 μG) like in the reverse shock.
We report on the detection of flaring activity from the Fanaroff-Riley I radio galaxy NGC 1275 in very-high-energy (VHE, E > 100 GeV) gamma rays with the Major Atmospheric Gamma Imaging Cherenkov ...(MAGIC) telescopes. The observations were performed between 2016 September and 2017 February, as part of a monitoring programme. The brightest outburst, with ∼1.5 times the Crab Nebula flux above 100 GeV (C.U.), was observed during the night between 2016 December 31 and 2017 January 1. The flux is fifty times higher than the mean flux previously measured in two observational campaigns between 2009 October and 2010 February and between 2010 August and 2011 February. Significant variability of the day-by-day light curve was measured. The shortest flux-doubling timescale was found to be of (611 ± 101) min. The spectra calculated for this period are harder and show a significant curvature with respect to the ones obtained in the previous campaigns. The combined spectrum of the MAGIC data during the strongest flare state and simultaneous data from the Fermi-LAT around 2017 January 1 follows a power law with an exponential cutoff at the energy (492 ± 35) GeV. We further present simultaneous optical flux density measurements in the R-band obtained with the Kungliga Vetenskaps Akademien (KVA) telescope and investigate the correlation between the optical and gamma-ray emission. Due to possible internal pair-production, the fast flux variability constrains the Doppler factor to values that are inconsistent with a large viewing angle as observed in the radio band. We investigate different scenarios for the explanation of fast gamma-ray variability, namely emission from magnetospheric gaps, relativistic blobs propagating in the jet (mini-jets), or an external cloud (or star) entering the jet. We find that the only plausible model to account for the luminosities here observed would be the production of gamma rays in a magnetospheric gap around the central black hole, only in the eventuality of an enhancement of the magnetic field threading the hole from its equipartition value with the gas pressure in the accretion flow. The observed gamma-ray flare therefore challenges all the discussed models for fast variability of VHE gamma-ray emission in active galactic nuclei.
Spontaneous breaking of Lorentz symmetry at energies on the order of the Planck energy or lower is predicted by many quantum gravity theories, implying non-trivial dispersion relations for the photon ...in vacuum. Consequently, gamma-rays of different energies, emitted simultaneously from astrophysical sources, could accumulate measurable differences in their time of flight until they reach the Earth. Such tests have been carried out in the past using fast variations of gamma-ray flux from pulsars, and more recently from active galactic nuclei and gamma-ray bursts. We present new constraints studying the gamma-ray emission of the galactic Crab Pulsar, recently observed up to TeV energies by the Major Atmospheric Gamma-ray Imaging Cherenkov (MAGIC) collaboration. A profile likelihood analysis of pulsar events reconstructed for energies above 400 GeV finds no significant variation in arrival time as their energy increases. Ninety-five percent CL limits are obtained on the effective Lorentz invariance violating energy scale at the level of ( ) for a linear, and ( ) for a quadratic scenario, for the subluminal and the superluminal cases, respectively. A substantial part of this study is dedicated to calibration of the test statistic, with respect to bias and coverage properties. Moreover, the limits take into account systematic uncertainties, which are found to worsen the statistical limits by about 36%-42%. Our constraints would have been much more stringent if the intrinsic pulse shape of the pulsar between 200 GeV and 400 GeV was understood in sufficient detail and allowed inclusion of events well below 400 GeV.
The microquasar V404 Cygni underwent a series of outbursts in 2015, June 15-31, during which its flux in hard X-rays (20-40 keV) reached about 40 times the Crab Nebula flux. Because of the ...exceptional interest of the flaring activity from this source, observations at several wavelengths were conducted. The MAGIC telescopes, triggered by the INTEGRAL alerts, followed-up the flaring source for several nights during the period June 18-27, for more than 10 hours. One hour of observation was conducted simultaneously to a giant 22 GHz radio flare and a hint of signal at GeV energies seen by Fermi-LAT. The MAGIC observations did not show significant emission in any of the analysed time intervals. The derived flux upper limit, in the energy range 200–1250 GeV, is 4.8×10$^{−12}$ ph cm$^{−2}$ s$^{−1}$. We estimate the gamma-ray opacity during the flaring period, which along with our non-detection, points to an inefficient acceleration in the V404 Cyg jets if VHE emitter is located further than 1 × 10$^{10}$ cm from the compact object.
Fibrodysplasia ossificans progressiva (FOP) is a severe, rare, autosomal dominant, ectopic ossifying condition, with primary involvement of the skeletal muscles associated with skeletal ...abnormalities. This report concerns an 11‐year‐old boy suffering from FOP, who presented signficant modification of the musculoskeletal structure of the thorax and problems with articular movements. The patient showed progress after treatment with ethane‐l‐hydroxyl, l‐diphosphonate (EHDP). In fact, using a scintiscanner we were able to observe a significant improvement in symptoms and a recovery of some of the active sites of ossification.
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