Association between serum Mg2+ concentrations and cardiovascular organ damage in a cohort of adult subjects

Magnesium (Mg2+) levels are associated with insulin resistance, hypertension, atherosclerosis, and type 2 diabetes (T2DM). We evaluated the clinical utility of physiological Mg2+ in assessing subclinical cardiovascular organ damage including increased carotid artery intima-media thickness (c-IMT) and left ventricular mass index (LVMI) in a cohort of well-characterized adult non-diabetic individuals. Age-and gender-adjusted correlations between Mg2+ and metabolic parameters showed that Mg2+ circulating levels were correlated negatively with body mass index (BMI), fasting glucose, and 2h-oral glucose tolerance test (OGTT) glucose. Similarly, Mg2+ levels were significantly and negatively related to c-IMT and LVMI. A multivariate regression analysis revealed that age (β = 0.440; p < 0.0001), BMI (β = 0.225; p < 0.0001), and Mg2+ concentration (β = −0.122; p < 0.01) were independently associated with c-IMT. Age (β = 0.244; p = 0.012), Mg2+ (β = −0.177; p = 0.019), and diastolic blood pressure (β = 0.184; p = 0.038) were significantly associated with LVMI in women, while age (β = 0.211; p = 0.019), Mg2+ (β = −0.171; p = 0.038) and the homeostasis model assessment index of insulin resistance (HOMA-IR) (β = −0.211; p = 0.041) were the sole variables associated with LVMI in men. In conclusion, our data support the hypothesis that the assessment of Mg2+ as part of the initial work-up might help unravel the presence of subclinical organ damage in subjects at increased risk of cardiovascular complications

The Blue Straggler Population in Dwarf Galaxies

In this chapter I review the recent developments regarding the study of Blue Stragglers (BSS) in dwarf galaxies. The loose density environment of dwarf galaxies resembles that of the Galactic Halo, hence it is natural to compare their common BSS properties. At the same time, it is unescapable to compare with the BSS properties in Galactic Globular clusters, which constitute the reference point for BSS studies. Admittedly, the literature on BSS in dwarf galaxies is not plentiful. The limitation is mostly due to the large distance to even the closest dwarf galaxies. Nevertheless, recent studies have allowed a deeper insight on the BSS photometric properties that are worth examining.Comment: Chapter 6, in Ecology of Blue Straggler Stars, H.M.J. Boffin, G. Carraro & G. Beccari (Eds), Astrophysics and Space Science Library, Springe

First spectroscopic investigation of Anomalous Cepheid variables

Anomalous Cepheids (ACEPs) are intermediate mass metal-poor pulsators mostly discovered in dwarf galaxies of the Local Group. However, recent Galactic surveys, including the Gaia DR3, found a few hundreds of ACEPs in the Milky Way. Their origin is not well understood. We aim to investigate the origin and evolution of Galactic ACEPs by studying for the first time the chemical composition of their atmospheres. We used UVES@VLT to obtain high-resolution spectra for a sample of 9 ACEPs belonging to the Galactic halo. We derived the abundances of 12 elements, including C, Na, Mg, Si, Ca, Sc, Ti, Cr, Fe, Ni, Y, and Ba. We complemented these data with literature abundances for an additional three ACEPs that were previously incorrectly classified as type II Cepheids, thus increasing the sample to a total of 12 stars. All the investigated ACEPs have an iron abundance [Fe/H]$<-1.5$ dex as expected from theoretical predictions for these pulsators. The abundance ratios of the different elements to iron show that the ACEP's chemical composition is generally consistent with that of the Galactic halo field stars, except the Sodium, which is found overabundant in 9 out of the 11 ACEPs where it was measured, in close similarity with second-generation stars in the Galactic Globular Clusters. The same comparison with dwarf and ultra-faint satellites of the Milky Way reveals more differences than similarities so it is unlikely that the bulk of Galactic ACEPs originated in such a kind of galaxies which subsequently dissolved in the Galactic halo. The principal finding of this work is the unexpected overabundance of Sodium in ACEPs. We explored several hypotheses to explain this feature, finding that the most promising scenario is the evolution of low-mass stars in a binary system with either mass transfer or merging. Detailed modelling is needed to confirm this hypothesis.Comment: 15 Figures, 4 Tables, Accepted for publication on Astronomy & Astrophysic

Pioglitazone corrects dysregulation of skeletal muscle mitochondrial proteins involved in ATP synthesis in type 2 diabetes

Context: In this study, we aimed to identify the determinants of mitochondrial dysfunction in skeletal muscle (SKLM) of subjects with type 2 diabetes (T2DM), and to evaluate the effect of pioglitazone (PIO) on SKLM mitochondrial proteome. Methods: Two different groups of adults were studied. Group I consisted of 8 individuals with normal glucose tolerance (NGT) and 8 with T2DM, subjected to SKLM mitochondrial proteome analysis by 2D-gel electrophoresis followed by mass spectrometry-based protein identification. Group II included 24 individuals with NGT and 24 with T2DM, whose SKLM biopsies were subjected to immunoblot analysis. Of the 24 subjects with T2DM, 20 were randomized to receive placebo or PIO (15 mg daily) for 6 months. After 6 months of treatment, SKLM biopsy was repeated. Results: Mitochondrial proteomic analysis on Group I revealed that several mitochondrial proteins involved in oxidative metabolism were differentially expressed between T2DM and NGT groups, with a downregulation of ATP synthase alpha chain (ATP5A), electron transfer flavoprotein alpha-subunit (ETFA), cytochrome c oxidase subunit VIb isoform 1 (CX6B1), pyruvate dehydrogenase protein X component (ODPX), dihydrolipoamide dehydrogenase (DLDH), dihydrolipoamide-S-succinyltransferase (DLST), and mitofilin, and an up-regulation of hydroxyacyl-CoA-dehydrogenase (HCDH), 3,2-trans-enoyl-CoA-isomerase (D3D2) and delta3,5-delta2,4-dienoyl-CoA-isomerase (ECH1) in T2DM as compared to NGT subjects. By immunoblot analysis on SKLM lysates obtained from Group II we confirmed that, in comparison to NGT subjects, those with T2DM exhibited lower protein levels of ATP5A (−30%, P = 0.006), ETFA (−50%, P = 0.02), CX6B1 (−30%, P = 0.03), key factors for ATP biosynthesis, and of the structural protein mitofilin (−30%, P = 0.01). T2DM was associated with a reduced abundance of the enzymes involved in the Krebs cycle DLST and ODPX (−20%, P ≤ 0.05) and increased levels of HCDH and ECH1, enzymes implicated in the fatty acid catabolism (+30%, P ≤ 0.05). In subjects with type 2 diabetes treated with PIO for 6 months we found a restored SKLM protein abundance of ATP5A, ETFA, CX6B1, and mitofilin. Moreover, protein levels of HCDH and ECH1 were reduced by −10% and − 15% respectively (P ≤ 0.05 for both) after PIO treatment. Conclusion: Type 2 diabetes is associated with reduced levels of mitochondrial proteins involved in oxidative phosphorylation and an increased abundance of enzymes implicated in fatty acid catabolism in SKLM. PIO treatment is able to improve SKLM mitochondrial proteomic profile in subjects with T2DM

The VMC survey - VIII : First results for anomalous Cepheids

The VISTA near-infrared YJKs survey of the Magellanic Clouds System (VMC, PI M.-R. L. Cioni) is collecting deep Ks-band time-series photometry of the pulsating variable stars hosted in the system formed by the two Magellanic Clouds and the Bridge connecting them. In this paper, we present for the first time Ks-band light curves for anomalous Cepheid (AC) variables. In particular, we have analysed a sample of 48 Large Magellanic Cloud ACs, for which identification and optical magnitudes were obtained from the OGLE III and IV catalogues. The VMC Ks-band light curves for ACs are well sampled, with the number of epochs ranging from 8 to 16, and allowing us to obtain very precise mean Ks magnitudes with errors on average of the order of 0.01 mag. The values were used to build the first period-luminosity and period-Wesenheit relations in the near-infrared for fundamental mode and first overtone ACs. At the same time we exploited the optical (V, I) OGLE data to build accurate period-luminosity, period-luminosity-colour and period-Wesenheit relations both for fundamental mode and first overtone ACs. For the first time, these relations were derived from a sample of pulsators which uniformly cover the whole AC instability strip. The application of the optical period-Wesenheit relation to a sample of dwarf galaxies hosting a significant population of ACs revealed that this relation is a valuable tool for deriving distances within the Local Group. Due to its lower dispersion, we expect the Ks period-Wesenheit relations first derived in this paper to represent a valuable tool for measuring accurate distances to galaxies hosting ACs when more data in near-infrared filters become available.Peer reviewe

Pulmonary metastasectomy versus continued active monitoring in colorectal cancer (PulMiCC): a multicentre randomised clinical trial

BACKGROUND: Lung metastasectomy in the treatment of advanced colorectal cancer has been widely adopted without good evidence of survival or palliative benefit. We aimed to test its effectiveness in a randomised controlled trial (RCT). METHODS: Multidisciplinary teams in 13 hospitals recruited participants with potentially resectable lung metastases to a multicentre, two-arm RCT comparing active monitoring with or without metastasectomy. Other local or systemic treatments were decided by the local team. Randomisation was remote and stratified by site with minimisation for age, sex, primary cancer stage, interval since primary resection, prior liver involvement, the number of metastases, and carcinoembryonic antigen level. The central Trial Management Group were blind to patient allocation until completion of the analysis. Analysis was on intention to treat with a margin for non-inferiority of 10%. RESULTS: Between December 2010 and December 2016, 65 participants were randomised. Characteristics were well-matched in the two arms and similar to those in reported studies: age 35 to 86 years (interquartile range (IQR) 60 to 74); primary resection IQR 16 to 35 months previously; stage at resection T1, 2 or 3 in 3, 8 and 46; N1 or N2 in 31 and 26; unknown in 8. Lung metastases 1 to 5 (median 2); 16/65 had previous liver metastases; carcinoembryonic antigen normal in 55/65. There were no other interventions in the first 6 months, no crossovers from control to treatment, and no treatment-related deaths or major adverse events. The Hazard ratio for death within 5 years, comparing metastasectomy with control, was 0.82 (95%CI 0.43, 1.56). CONCLUSIONS: Because of poor and worsening recruitment, the study was stopped. The small number of participants in the trial (N = 65) precludes a conclusive answer to the research question given the large overlap in the confidence intervals in the proportions still alive at all time points. A widely held belief is that the 5-year absolute survival benefit with metastasectomy is about 35%: 40% after metastasectomy compared to < 5% in controls. The estimated survival in this study was 38% (23-62%) for metastasectomy patients and 29% (16-52%) in the well-matched controls. That is the new and important finding of this RCT. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT01106261. Registered on 19 April 2010

Defining anti-synthetase syndrome: a systematic literature review

OBJECTIVES: Anti-synthetase syndrome (ASSD) is a heterogeneous autoimmune disease characterised by multi-system involvement with a wide variety of manifestations. Validated classification criteria are necessary to improve recognition and prevent misclassification, especially given the lack of reliable and standardised autoantibody testing. We systematically reviewed the literature to analyse proposed ASSD criteria, characteristics, and diagnostic performance. METHODS: We searched PubMed and Embase databases (01/01/1984 to 06/11/2018) and the ACR and EULAR meeting abstracts (2017-2018). Sensitivities, specificities, positive, negative likelihood ratios and risk of bias were calculated for ASSD criteria and key variables reported in the literature. We performed meta-analysis when appropriate. RESULTS: We retrieved 4,358 studies. We found 85 proposed ASSD criteria from a total of 82 studies. All but one study included anti-synthetase autoantibody (ARS) positivity in the ASSD criteria. Most studies required only one ASSD feature plus anti-ARS to define ASSD (n=64, 78%), whereas 16 studies required more than one ASSD variable plus anti-ARS. The only criteria not including anti-ARS positivity required 5 ASSD clinical features. We found limited data and wide variability in the diagnostic performance of each variable and definition proposed in the literature. Given these limitations we only meta-analysed the performance of individual muscle biopsy and clinical variables in diagnosing ASSD, which performed poorly. CONCLUSIONS: The current ASSD criteria include a variety of serological, clinical, and histological features with wide variability amongst proposed definitions and the performance of these definitions has not been tested. This systematic literature review suggests the need for additional data and consensus-driven classification criteria for ASSD

The VMC Survey. V. First results for Classical Cepheids

The VISTA Magellanic Cloud (VMC, PI M.R. Cioni) survey is collecting deep Ks-band time-series photometry of the pulsating variable stars hosted by the system formed by the two Magellanic Clouds (MCs) and the "bridge" connecting them. In this paper we present the first results for Classical Cepheids, from the VMC observations of two fields in the Large Magellanic Cloud (LMC). The VMC Ks-band light curves of the Cepheids are well sampled (12-epochs) and of excellent precision. We were able to measure for the first time the Ks magnitude of the faintest Classical Cepheids in the LMC (Ks\sim17.5 mag), which are mostly pulsating in the First Overtone (FO) mode, and to obtain FO Period-Luminosity (PL), Period-Wesenheit (PW), and Period-Luminosity-Color (PLC) relations, spanning the full period range from 0.25 to 6 day. Since the longest period Cepheid in our dataset has a variability period of 23 day, we have complemented our sample with literature data for brighter F Cepheids. On this basis we have built a PL relation in the Ks band that, for the first time, includes short period pulsators, and spans the whole range from 1.6 to 100 days in period. We also provide the first ever empirical PW and PLC relations using the (V-Ks) color and time-series Ks photometry. The very small dispersion (\sim0.07 mag) of these relations makes them very well suited to study the three-dimensional (3D) geometry of the Magellanic system. The use of "direct" (parallax- and Baade-Wesselink- based) distance measurements to both Galactic and LMC Cepheids, allowed us to calibrate the zero points of the PL, PW, and PLC relations obtained in this paper, and in turn to estimate an absolute distance modulus of (m-M)0=18.46\pm0.03 for the LMC. This result is in agreement with most of the latest literature determinations based on Classical Cepheids.Comment: 12 pages, 7 figures: MNRAS in pres

Quantum value indefiniteness

The indeterministic outcome of a measurement of an individual quantum is certified by the impossibility of the simultaneous, definite, deterministic pre-existence of all conceivable observables from physical conditions of that quantum alone. We discuss possible interpretations and consequences for quantum oracles.Comment: 19 pages, 2 tables, 2 figures; contribution to PC0