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Postabsorptive and Insulin-Stimulated Energy Homeostasis and Leucine Turnover in Offspring of Type 2 Diabetic Patients Guido Lattuada , PHD 1 , Lucia Piceni Sereni , MD 1 , Dora Ruggieri , PHD 1 , Antonella Scollo , RN 1 , Stefano Benedini , MD, PHD 1 , Francesca Ragogna , PHD 1 , Federica Costantino , PHD 1 , Alberto Battezzati , MD, PHD 1 2 , Livio Luzi , MD 1 2 3 4 and Gianluca Perseghin , MD 1 3 1 Internal Medicine, Section of Nutrition/Metabolism, Istituto Scientifico H San Raffaele, Milan, Italy 2 International Center for the Assessment of Nutritional Status, Milan, Italy 3 Unit of Clinical Spectroscopy, Istituto Scientifico H San Raffaele, Milan Italy 4 Faculty of Exercise Sciences, Università degli Studi di Milano, Milan, Italy Address correspondence and reprint requests to Gianluca Perseghin, MD, Istituto Scientifico H San Raffaele, Internal Medicine, Section of Nutrition/Metabolism & Unit of Clinical Spectroscopy via Olgettina 60, 20132, Milan, Italy. E-mail: perseghin.gianluca{at}hsr.it Abstract OBJECTIVE —This study was performed to ascertain whether insulin resistance with respect to protein metabolism is an additional primary metabolic abnormality affecting insulin-resistant offspring of type 2 diabetic parents, along with insulin resistance with respect to glucose and lipid metabolism. RESEARCH DESIGN AND METHODS —We studied 18 young, nonobese offspring of type 2 diabetic parents and 27 healthy matched (by means of dual-energy X-ray absorption) individuals with the bolus plus continuous infusion of [6,6- 2 H 2 ]glucose and [1- 13 C]leucine in combination with the insulin clamp (40 mU · m –2 · min −1 ). RESULTS —Fasting plasma leucine, phenylalanine, alanine, and glutamine concentrations, as well as the glucose and leucine turnover (reciprocal pool model: 155 ± 10 vs. 165 ± 5 μmol · kg lean body mass –1 · h −1 in offspring of type 2 diabetic patients and healthy matched individuals, respectively), were also not different. During the clamp, glucose turnover rates were significantly reduced in offspring of type 2 diabetic patients (7.1 ± 0.5) in comparison with healthy matched individuals (9.9 ± 0.6 mg · kg lean body mass –1 · min −1 ; P < 0.01). Also, the suppression of leucine turnover was impaired in offspring of type 2 diabetic patients (12 ± 1%) in comparison with healthy matched individuals (17 ± 1%; P = 0.04) and correlated with the degree of the impairment of insulin-stimulated glucose metabolism ( R 2 = 0.13; P = 0.02). CONCLUSIONS —Nonobese, nondiabetic, insulin-resistant offspring of type 2 diabetic patients were characterized by an impairment of insulin-dependent suppression of protein breakdown, which was proportional to the impairment of glucose metabolism. These results demonstrate that in humans, a primary in vivo impairment of insulin action affects glucose and fatty acid metabolism as previously shown and also protein/amino acid metabolism. ELF, endogenous leucine flux FFA, free fatty acid REE, resting energy expenditure α-TNF-R2, α-tumor necrosis factor receptor-2 Footnotes A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Accepted August 8, 2004. Received June 18, 2004. DIABETES CARE

ObjectiveTrimetazidine may have beneficial effects on left ventricular (LV) function in patients with systolic heart failure. The authors assessed whether long-term addition of trimetazidine to conventional treatment could improve, along with LV function, resting whole body energy metabolism in patients with chronic systolic heart failure.DesignSingle blind randomised study.SettingUniversity Hospital.Patients44 patients with systolic heart failure receiving full medical treatment.InterventionsIndirect calorimetry and two-dimensional echocardiography at baseline and after 3 months.Main outcome measuresWhole body resting energy expenditure (REE), percentage of predicted REE, LV ejection fraction (EF), NYHA class, quality of life.ResultsTrimetazidine increased EF compared with conventional therapy alone (from 35±8% to 42±11% vs from 35±7% to 36±6%; p=0.02, analysis of variance for repeated measures). NYHA class and quality of life also improved compared with conventional therapy (p<0.0001). REE (from 1677±264 to 1580±263 kcal/day) and percentage of predicted REE (based on the Harris–Benedict equation: from 114±10% to 108±9%) decreased in the trimetazidine group, but not in the control group (REE from 1679±304 to 1690±337 kcal/day and percentage of predicted REE from 113±12% to 115±14%). The variation was different between groups (p=0.03 and 0.023, respectively).ConclusionsIn patients with systolic heart failure, improvement in functional class and LV function induced by middle-term trimetazidine therapy is paralleled by a reduction in whole body REE. The beneficial cardiac effects of trimetazidine may be also mediated by a peripheral metabolic effect.

The aerosol properties of Mount Etna’s passive degassing plume and its short-term processes and radiative impact were studied in detail during the EPL-RADIO campaigns (summer 2016–2017), using a synergistic combination of observations and radiative transfer modelling. Summit observations show extremely high particulate matter concentrations. Using portable photometers, the first mapping of small-scale (within ∼ 20 km from the degassing craters) spatial variability of the average size and coarse-to-fine burden proportion of volcanic aerosols is obtained. A substantial variability of the plume properties is found at these spatial scales, revealing that processes (e.g. new particle formation and/or coarse aerosols sedimentation) are at play, which are not represented with current regional scale modelling and satellite observations. Statistically significant progressively smaller particles and decreasing coarse-to-fine particles burden proportion are found along plume dispersion. Vertical structures of typical passive degassing plumes are also obtained using observations from a fixed LiDAR station constrained with quasi-simultaneous photometric observations. These observations are used as input to radiative transfer calculations, to obtain the shortwave top of the atmosphere (TOA) and surface radiative effect of the plume. For a plume with an ultraviolet aerosol optical depth of 0.12–0.14, daily average radiative forcings of - 4.5 and - 7.0 W/m 2 , at TOA and surface, are found at a fixed location ∼ 7 km downwind the degassing craters. This is the first available estimation in the literature of the local radiative impact of a passive degassing volcanic plume.

An innovative mobile lidar device, developed to monitor volcanic plumes during explosive eruptions at Mt. Etna (Italy) and to analyse the optical properties of volcanic particles, was upgraded in October 2023 with the aim of improving volcanic plume retrievals. The new configuration of the lidar allows it to obtain new data on both the optical and the microphysical properties of the atmospheric aerosol. In fact, after the upgrade, the lidar is able to measure three backscattering coefficients, two extinction coefficients and two depolarisation ratios in a configuration defined as “state-of-the-art lidar”, where properties such as particle size distribution and the refractive index can be derived. During the lidar implementation, we were able to test the system’s performance through specific calibration measurements. A comparison in an aerosol-free region (7.2–12 km) between lidar signals at 1064 nm, 532 nm and 355 nm and the corresponding pure molecular profiles showed a relative difference of <1% between them for all the wavelengths, highlighting the good dynamic of the signals. The overlap correction allowed us to reduce the underestimation of the backscattering coefficient from 50% to 10% below 450 m and 750 m at both 355 and 532 nm, respectively. The correct alignment between the laser beam and the receiver optical chain was tested using the signal received from the different quadrants of the telescope, and the relative differences between the four directions were comparable to zero, within the margin of error. Finally, the first measurement results are shown and compared with results obtained by other instruments, with the aim of proving the ability of the upgraded system to more precisely characterise aerosol optical and microphysical properties.

Risk of relapse or progression remains high in the treatment of most patients with epithelial ovarian cancer, and development of a molecular predictor could be a valuable tool for stratification of patients by risk. We aimed to develop a microRNA (miRNA)-based molecular classifier that can predict risk of progression or relapse in patients with epithelial ovarian cancer. We analysed miRNA expression profiles in three cohorts of samples collected at diagnosis. We used 179 samples from a Multicenter Italian Trial in Ovarian cancer trial (cohort OC179) to develop the model and 263 samples from two cancer centres (cohort OC263) and 452 samples from The Cancer Genome Atlas epithelial ovarian cancer series (cohort OC452) to validate the model. The primary clinical endpoint was progression-free survival, and we adapted a semi-supervised prediction method to the miRNA expression profile of OC179 to identify miRNAs that predict risk of progression. We assessed the independent prognostic role of the model using multivariable analysis with a Cox regression model. We identified 35 miRNAs that predicted risk of progression or relapse and used them to create a prognostic model, the 35-miRNA-based predictor of Risk of Ovarian Cancer Relapse or progression (MiROvaR). MiROvaR was able to classify patients in OC179 into a high-risk group (89 patients; median progression-free survival 18 months [95% CI 15–22]) and a low-risk group (90 patients; median progression-free survival 38 months [24–not estimable]; hazard ratio [HR] 1·85 [1·29–2·64], p=0·00082). MiROvaR was a significant predictor of progression in the two validation sets (OC263 HR 3·16, 95% CI 2·33–4·29, p<0·0001; OC452 HR 1·39, 95% CI 1·11–1·74, p=0·0047) and maintained its independent prognostic effect when adjusted for relevant clinical covariates using multivariable analyses (OC179: adjusted HR 1·48, 95% CI 1·03–2·13, p=0·036; OC263: adjusted HR 3·09 [2·24–4·28], p<0·0001; and OC452: HR 1·41 [1·11–1·79], p=0·0047). MiROvaR is a potential predictor of epithelial ovarian cancer progression and has prognostic value independent of relevant clinical covariates. MiROvaR warrants further investigation for the development of a clinical-grade prognostic assay. AIRC and CARIPLO Foundation.

Lidar observations are very useful to analyse dispersed volcanic clouds in the troposphere mainly because of their high range resolution, providing morphological as well as microphysical (size and mass) properties. In this work, we analyse the volcanic cloud of 18 May 2016 at Mt. Etna, in Italy, retrieved by polarimetric dual-wavelength Lidar measurements. We use the AMPLE (Aerosol Multi-Wavelength Polarization Lidar Experiment) system, located in Catania, about 25 km from the Etna summit craters, pointing at a thin volcanic cloud layer, clearly visible and dispersed from the summit craters at the altitude between 2 and 4 km and 6 and 7 km above the sea level. Both the backscattering and linear depolarization profiles at 355 nm (UV, ultraviolet) and 532 nm (VIS, visible) wavelengths, respectively, were obtained using different angles at 20°, 30°, 40° and 90°. The proposed approach inverts the Lidar measurements with a physically based inversion methodology named Volcanic Ash Lidar Retrieval (VALR), based on Maximum-Likelihood (ML). VALRML can provide estimates of volcanic ash mean size and mass concentration at a resolution of few tens of meters. We also compared those results with two methods: Single-variate Regression (SR) and Multi-variate Regression (MR). SR uses the backscattering coefficient or backscattering and depolarization coefficients of one wavelength (UV or VIS in our cases). The MR method uses the backscattering coefficient of both wavelengths (UV and VIS). In absence of in situ airborne validation data, the discrepancy among the different retrieval techniques is estimated with respect to the VALR ML algorithm. The VALR ML analysis provides ash concentrations between about 0.1 μg/m3 and 1 mg/m3 and particle mean sizes of 0.1 μm and 6 μm, respectively. Results show that, for the SR method differences are less than <10%, using the backscattering coefficient only and backscattering and depolarization coefficients. Moreover, we find differences of 20–30% respect to VALR ML, considering well-known parametric retrieval methods. VALR algorithms show how a physics-based inversion approaches can effectively exploit the spectral-polarimetric Lidar AMPLE capability.

The aim of this study was to analyze the feasibility and reliability of using hair as a matrix to determine the dehydroepiandrosterone (DHEA) and sexual steroid concentrations and the cortisol/DHEA ratio in fattening pigs. The results could be also used to plan future research to identify threshold values in order to set up strategies to control the allostatic load and increase the resilience of fattening pigs before slaughter. The study was conducted on 107 commercial crossbred rearing pigs. The hair samples were taken by shaving at the age of 36 weeks, and concentrations of the hormones were measured using a solid-phase microtiter radioimmunoassay. Females had significantly higher cortisol levels (p < 0.01), significantly lower DHEA concentrations (p < 0.05) and significantly higher cortisol/DHEA ratios (p < 0.01) than barrows. Progesterone was significantly higher in gilts than in barrows (p < 0.01). Testosterone and 17β-estradiol were significantly higher in barrows than in gilts (p < 0.05). If future research can produce threshold values for the different markers examined, the evaluation of animals under subclinical stress conditions will be possible.

Volcanic emissions are a well-known hazard that can have serious impacts on local populations and aviation operations. Whereas several remote sensing observations detect high-intensity explosive eruptions, few studies focus on low intensity and long-lasting volcanic emissions. In this work, we have managed to fully characterize those events by analyzing the volcanic plume produced on the last day of the 2018 Christmas eruption at Mt. Etna, in Italy. We combined data from a visible calibrated camera, a multi-wavelength elastic/Raman Lidar system, from SEVIRI (EUMETSAT-MSG) and MODIS (NASA-Terra/Aqua) satellites and, for the first time, data from an automatic sun-photometer of the aerosol robotic network (AERONET). Results show that the volcanic plume height, ranging between 4.5 and 6 km at the source, decreased by about 0.5 km after 25 km. Moreover, the volcanic plume was detectable by the satellites up to a distance of about 400 km and contained very fine particles with a mean effective radius of about 7 µm. In some time intervals, volcanic ash mass concentration values were around the aviation safety thresholds of 2 × 10−3 g m−3. Of note, Lidar observations show two main stratifications of about 0.25 km, which were not observed at the volcanic source. The presence of the double stratification could have important implications on satellite retrievals, which usually consider only one plume layer. This work gives new details on the main features of volcanic plumes produced during low intensity and long-lasting volcanic plume emissions.

Background: Recently, questions around the efficacy and effectiveness of Fractional Flow Reserve (FFR) have arisen in various clinical settings. Methods: The Clinical Outcome of FFR-guided Revascularization Strategy of Coronary Lesions (HALE-BOPP) study is an investigator-initiated, multicentre, international prospective study enrolling patients who underwent FFR measurement on at least one vessel. In accordance with the decision-making workflow and treatment, the vessels were classified in three subgroups: (i) angio-revascularized, (ii) FFR-revascularized, (iii) FFR-deferred. The primary endpoint was the occurrence of target vessel failure (TVF, cardiac death, target vessel myocardial infarction and ischemia-driven target vessel revascularization). The analysis was carried out at vessel- and patient-level. Results: 1305 patients with 2422 diseased vessels fulfilled the criteria for the present analysis. Wire-related pitfalls and transient adenosine-related side effects occurred in 0.8% (95% CI: 0.4%–1.4%) and 3.3% (95% CI: 2.5%–4.3%) of cases, respectively. In FFR-deferred vessels, the overall incidence rate of TVF was 0.024 (95% CI: 0.019–0.031) lesion/year. After a median follow-up of 3.6 years, the occurrence of TVF was 6%, 7% and 11.7% in FFR-deferred, FFR-revascularized and angio-revascularized vessels, respectively. Compared to angio-revascularized vessels, FFR-guided vessels (both FFR-revascularized and FFR-deferred vessels) showed a lower TVF incidence rate lesion/year (0.029, 95% CI: 0.024–0.034 vs. 0.049, 95% CI: 0.040–0.061 respectively, p = 0.0001). The result was consistent after correction for confounding factors and across subgroups of clinical interest. The patient-level analysis confirmed the lower occurrence of TVF in negative-FFR vs. positive-FFR subgroups. Conclusions: In a large prospective observational study, an FFR-based strategy for the deferral of coronary lesions is a reliable and safe tool, associated with good outcomes. Clinical Trial Registration: NCT03079739.

In this paper, we use data obtained from LiDAR measurements during an ash emission event on 15 November 2010 at Mt. Etna, in Italy, in order to evaluate the spatial distribution of volcanic ash in the atmosphere. A scanning LiDAR system, located at 7 km distance from the summit craters, was directed toward the volcanic vents and moved in azimuth and elevation to analyse different volcanic plume sections. During the measurements, ash emission from the North East Crater and high degassing from the Bocca Nuova Crater were clearly visible. From our analysis we were able to: (1) evaluate the region affected by the volcanic plume presence; (2) distinguish volcanic plumes containing spherical aerosols from those having non-spherical ones; and (3) estimate the frequency of volcanic ash emissions. Moreover, the spatial distribution of ash mass concentration was evaluated with an uncertainty of about 50 %. We found that, even during ash emission episodes characterised by low intensity like the 15 November 2010 event, the region in proximity of the summit craters should be avoided by air traffic operations, the ash concentration being greater than 4 × 10 −3  g/m 3 . The use of a scanning permanent LiDAR station may usefully monitor the volcanic activity and help to drastically reduce the risks to aviation operations during the frequent Etna eruptions.