Circulating SIRT1 inversely correlates with epicardial fat thickness in patients with obesity

Background and aim: Obesity is increasing worldwide and is related to undesirable cardiovascular outcomes. Epicardial fat (EF), the heart visceral fat depot, increases with obesity and correlates with cardiovascular risk. SIRT1, an enzyme regulating metabolic circuits linked with obesity, has a cardioprotective effect and is a predictor of cardiovascular events. We aimed to assess the relationship of EF thickness (EFT) with circulating SIRT1 in patients with obesity. Methods and results: Sixty-two patients affected by obesity and 23 lean controls were studied. Plasma SIRT1 concentration was determined by enzyme-linked immunosorbent assay (ELISA). EFT was measured by echocardiography. Body mass index (BMI), waist circumference, heart rate (HR), blood pressure, and laboratory findings (fasting glucose, insulin, HbA1c, cholesterol, and triglycerides) were assessed. SIRT1 was significantly lower (P = 0.002) and EFT was higher (P < 0.0001) in patients with obesity compared with lean controls. SIRT1 showed a negative correlation with EFT and HR in the obesity group (rho = -0.350, P = 0.005; rho = -0.303, P = 0.008, respectively). After adjustment for obesity-correlated variables, multiple linear regression analysis showed that EFT remained the best correlate of SIRT1 (beta = -0.352, P = 0.016). Conclusions: Circulating SIRT1 correlates with the visceral fat content of the heart. Serum SIRT1 levels might provide additional information for risk assessment of coronary artery disease in patients with obesity. (C) 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved

Mangosteen Extract Shows a Potent Insulin Sensitizing Effect in Obese Female Patients: A Prospective Randomized Controlled Pilot Study.

There is a widely acknowledged association between insulin resistance and obesity/type 2 diabetes (T2DM), and insulin sensitizing treatments have proved effective in preventing diabetes and inducing weight loss. Obesity and T2DM are also associated with increased inflammation. Mangosteen is a tropical tree, whose fruits—known for their antioxidant properties—have been recently suggested having a possible further role in the treatment of obesity and T2DM. The objective of this pilot study has been to evaluate safety and efficacy of treatment with mangosteen extract on insulin resistance, weight management, and inflammatory status in obese female patients with insulin resistance. Twenty-two patients were randomized 1:1 to behavioral therapy alone or behavioral therapy and mangosteen and 20 completed the 26-week study. The mangosteen group reported a significant improvement in insulin sensitivity (homeostatic model assessment-insulin resistance, HOMA-IR −53.22% vs. −15.23%, p = 0.004), and no side effect attributable to treatment was reported. Given the positive preliminary results we report and the excellent safety profile, we suggest a possible supplementary role of mangosteen extracts in the treatment of obesity, insulin resistance, and inflammation

Overweight and obese patients with nickel allergy have a worse metabolic profile compared to weight matched non-allergic individuals

A lack of balance between energy intake and expenditure due to overeating or reduced physical activity does not seem to explain entirely the obesity epidemic we are facing, and further factors are therefore being evaluated. Nickel (Ni) is a ubiquitous heavy metal implied in several health conditions. Regarding this, the European Food Safety Authority has recently released an alert on the possible deleterious effects of dietary Ni on human health given the current levels of Ni dietary intake in some countries. Pre-clinical studies have also suggested its role as an endocrine disruptor and have linked its exposure to energy metabolism and glucose homeostasis dysregulation. Ni allergy is common in the general population, but preliminary data suggest it being even more widespread among overweight patients. OBJECTIVES: The aim of this study has been to evaluate the presence of Ni allergy and its association with the metabolic and endocrine profile in overweight and obese individuals. METHODS: We have evaluated 1128 consecutive overweight and obese outpatients. 784 were suspected of being allergic to Ni and 666 were assessed for it. Presence of Ni allergy and correlation with body mass index (BMI), body composition, metabolic parameters and hormonal levels were evaluated. RESULTS: We report that Ni allergy is more frequent in presence of weight excess and is associated with worse metabolic parameters and impaired Growth Hormone secretion. CONCLUSIONS: We confirm that Ni allergy is more common in obese patients, and we report for the first time its association with worse metabolic parameters and impaired function of the GH-IGF1 axis in human subjects

Inverse association of circulating SIRT1 and adiposity. A study on underweight, normal weight, and obese patients

Context: Sirtuins (SIRTs) are NAD+-dependent deacetylases, cellular sensors to detect energy availability, and modulate metabolic processes. SIRT1, the most studied family member, influences a number of tissues including adipose tissue. Expression and activity of SIRT1 reduce with weight gain and increase in conditions of starvation. Objective: To focus on SIRT1 plasma concentrations in different conditions of adiposity and to correlate SIRT1 with fat content and distribution, energy homeostasis and inflammation in under-weight, normal-weight, and obese individuals. Materials and Methods: 21 patients with anorexia nervosa, 26 normal-weight and 75 patients with obesity were evaluated. Body fat composition by dual-energy X-ray absorptiometry, ultrasound liver adiposity, echocardiographic epicardial fat thickness (EFT), inflammatory (ESR, CRP, and fibrinogen), and metabolic (FPG, insulin, LDL- and HDL-cholesterol, triglycerides) parameters, calculated basal metabolic rate (BMR) and plasma SIRT1 (ELISA) were measured. Results: SIRT1 was significantly higher in anorexic patients compared to normal-weight and obese patients (3.27 ± 2.98, 2.27 ± 1.13, and 1.36 ± 1.31 ng/ml, respectively). Linear regression models for each predictor variable adjusted for age and sex showed that SIRT1 concentration was inversely and significantly correlated with EFT, fat mass %, liver fat content, BMR, weight, BMI, WC, LDL-cholesterol, insulin, ESR. Stepwise multiple regression analysis revealed that age and EFT were the best independent correlates of SIRT1 (β = -0.026 ± 0.011, p = 0.025, and β = -0.516 ± 0.083, p < 0.001, respectively). Conclusions: Plasma SIRT1 shows a continuous pattern that inversely follows the whole spectrum of adiposity. SIRT1 significantly associates with EFT, a strong index of visceral fat phenotype, better than other indexes of adiposity studied here

Testicular histopathology, semen analysis and FSH, predictive value of sperm retrieval: supportive counseling in case of reoperation after testicular sperm extraction (TESE)

Background: To provide indicators for the likelihood of sperm retrieval in patients undergoing testicular sperm extraction is a major issue in the management of male infertility by TESE. The aim of our study was to determine the impact of different parameters, including testicular histopathology, on sperm retrieval in case of reoperation in patients undergoing testicular sperm extraction. Methods: We retrospectively analyzed 486 patients who underwent sperm extraction for intracytoplasmic sperm injection and testicular biopsy. Histology was classified into: normal spermatogenesis; hypospermatogenesis (reduction in the number of normal spermatogenetic cells); maturation arrest (absence of the later stages of spermatogenesis); and Sertoli cell only (absence of germ cells). Semen analysis and serum FSH, LH and testosterone were measured. Results: Four hundred thirty patients had non obstructive azoospermia, 53 severe oligozoospermia and 3 necrozoospermia. There were 307 (63%) successful sperm retrieval. Higher testicular volume, lower levels of FSH, and better histological features were predictive for sperm retrieval. The same parameters and younger age were predictive factors for shorter time for sperm recovery. After multivariable analysis, younger age, better semen parameters, better histological features and lower values of FSH remained predictive for shorter time for sperm retrieval while better semen and histology remained predictive factors for successful sperm retrieval. The predictive capacity of a score obtained by summing the points assigned for selected predictors (1 point for Sertoli cell only, 0.33 points for azoospermia, 0.004 points for each FSH mIU/ml) gave an area under the ROC curve of 0.843. Conclusions: This model can help the practitioner with counseling infertile men by reliably predicting the chance of obtaining spermatozoa with testicular sperm extraction when a repeat attempt is planne

Gleam: the GLAST Large Area Telescope Simulation Framework

This paper presents the simulation of the GLAST high energy gamma-ray telescope. The simulation package, written in C++, is based on the Geant4 toolkit, and it is integrated into a general framework used to process events. A detailed simulation of the electronic signals inside Silicon detectors has been provided and it is used for the particle tracking, which is handled by a dedicated software. A unique repository for the geometrical description of the detector has been realized using the XML language and a C++ library to access this information has been designed and implemented.Comment: 10 pages, Late

Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity.

Most monogenic cases of obesity in humans have been linked to mutations in genes encoding members of the leptin-melanocortin pathway. Specifically, mutations in MC4R, the melanocortin-4 receptor gene, account for 3-5% of all severe obesity cases in humans1-3. Recently, ADCY3 (adenylyl cyclase 3) gene mutations have been implicated in obesity4,5. ADCY3 localizes to the primary cilia of neurons 6 , organelles that function as hubs for select signaling pathways. Mutations that disrupt the functions of primary cilia cause ciliopathies, rare recessive pleiotropic diseases in which obesity is a cardinal manifestation 7 . We demonstrate that MC4R colocalizes with ADCY3 at the primary cilia of a subset of hypothalamic neurons, that obesity-associated MC4R mutations impair ciliary localization and that inhibition of adenylyl cyclase signaling at the primary cilia of these neurons increases body weight. These data suggest that impaired signaling from the primary cilia of MC4R neurons is a common pathway underlying&nbsp;genetic causes of obesity in humans

Psoriatic arthritis: imaging techniques

Imaging techniques to assess psoriatic arthritis (PsA) include radiography, ultrasonography (US), magnetic resonance imaging (MRI), computed tomography (CT) and bone scintigraphy. The radiographic hallmark of PsA is the combination of destructive changes (joint erosions, tuft resorption, osteolysis) with bone proliferation (including periarticular and shaft periostitis, ankylosis, spur formation and non-marginal syndesmophytes). US has an increasing important role in the evaluation of PsA. In fact, power Doppler US is useful mainly for its ability to assess musculoskeletal (joints, tendons, entheses) and cutaneous (skin and nails) involvement, to monitor efficacy of therapy and to guide steroid injections at the level of inflamed joints, tendon sheaths and entheses. MRI allows direct visualization of inflammation in peripheral and axial joints, and peripheral and axial entheses, and has dramatically improved the possibilities for early diagnosis and objective monitoring of the disease process in PsA. MRI has allowed explaining the relationships among enthesitis, synovitis and osteitis in PsA, supporting a SpA pattern of inflammation where enthesitis is the primary target of inflammation. CT has little role in assessment of peripheral joints, but it may be useful in assessing elements of spine disease. CT accuracy is similar to MRI in assessment of erosions in sacroiliac joint involvement, but CT is not as effective in detecting synovial inflammation. Bone scintigraphy lacks specificity and is now supplanted with US and MRI techniques

Search for Early Gamma-ray Production in Supernovae Located in a Dense Circumstellar Medium with the Fermi LAT

Supernovae (SNe) exploding in a dense circumstellar medium (CSM) are hypothesized to accelerate cosmic rays in collisionless shocks and emit GeV gamma rays and TeV neutrinos on a time scale of several months. We perform the first systematic search for gamma-ray emission in Fermi LAT data in the energy range from 100 MeV to 300 GeV from the ensemble of 147 SNe Type IIn exploding in dense CSM. We search for a gamma-ray excess at each SNe location in a one year time window. In order to enhance a possible weak signal, we simultaneously study the closest and optically brightest sources of our sample in a joint-likelihood analysis in three different time windows (1 year, 6 months and 3 months). For the most promising source of the sample, SN 2010jl (PTF10aaxf), we repeat the analysis with an extended time window lasting 4.5 years. We do not find a significant excess in gamma rays for any individual source nor for the combined sources and provide model-independent flux upper limits for both cases. In addition, we derive limits on the gamma-ray luminosity and the ratio of gamma-ray-to-optical luminosity ratio as a function of the index of the proton injection spectrum assuming a generic gamma-ray production model. Furthermore, we present detailed flux predictions based on multi-wavelength observations and the corresponding flux upper limit at 95% confidence level (CL) for the source SN 2010jl (PTF10aaxf).Comment: Accepted for publication in ApJ. Corresponding author: A. Franckowiak ([email protected]), updated author list and acknowledgement

Measurement of the branching ratio of the decay Ξ0→Σ+μ−νˉμ\Xi^{0}\rightarrow \Sigma^{+} \mu^{-} \bar{\nu}_{\mu}

From the 2002 data taking with a neutral kaon beam extracted from the CERN-SPS, the NA48/1 experiment observed 97 $\Xi^{0}\rightarrow \Sigma^{+} \mu^{-} \bar{\nu}_{\mu}$ candidates with a background contamination of $30.8 \pm 4.2$ events. From this sample, the BR($\Xi^{0}\rightarrow \Sigma^{+} \mu^{-} \bar{\nu}_{\mu}$) is measured to be $(2.17 \pm 0.32_{\mathrm{stat}}\pm 0.17_{\mathrm{syst}})\times10^{-6}$