Physical activity has numerous beneficial effects on metabolic and inflammatory processes

Obesity is a long-term multifactorial chronic disease, characterized by energy imbalance, due to an excess of caloric intake compared to energy expenditure and deregulation of other metabolic parameters, as, altered lipid profile, increased insulin resistance and chronic pro-inflammatory state. A healthy lifestyle, characterized by hypocaloric diet and physical activity, is important to reduce a chronic inflammation, oxidative stress and metabolic disorders typical of obesity. It is well known that the chronic inflammation state and oxidative stress are responsible for the aging and development of many diseases, such as cancer. In the light of these evidences, the aim of this study is to analyse body composition, metabolic profile and oxidative stress levels in obese patients subjected to a physical activity program before and after weight loss. We analysed the glycaemic and lipid profile, body composition such as visceral adipose tissue (VAT), fat mass (FM), and the dROMs serum levels via the Fenton's reaction. We found that in obese patients before physical activity intervention there are higher levels in dROMs serum levels, altered glycaemic and lipid profile and body composition compared to obese patients after physical activity intervention. In conclusion, the physical activity has numerous beneficial effects in obesity, modulating not only metabolic profile but also inflammatory and oxidative stress response

FAN1-MLH1 interaction affects repair of DNA interstrand cross-links and slipped-CAG/CTG repeats

FAN1, a DNA structure-specific nuclease, interacts with MLH1, but the repair pathways in which this complex acts are unknown. FAN1 processes DNA interstrand crosslinks (ICLs) and FAN1 variants are modifiers of the neurodegenerative Huntington's disease (HD), presumably by regulating HD-causing CAG repeat expansions. Here, we identify specific amino acid residues in two adjacent FAN1 motifs that are critical for MLH1 binding. Disruption of the FAN1-MLH1 interaction confers cellular hypersensitivity to ICL damage and defective repair of CAG/CTG slip-outs, intermediates of repeat expansion mutations. FAN1-S126 phosphorylation, which hinders FAN1-MLH1 association, is cell cycle-regulated by cyclin-dependent kinase activity and attenuated upon ICL induction. Our data highlight the FAN1-MLH1 complex as a phosphorylation-regulated determinant of ICL response and repeat stability, opening novel paths to modify cancer and neurodegeneration

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Il terzo settore attraverso le parole degli intervistati

Che cosa resta quando la crisi economica erode la coesione sociale, quando messaggi razzisti coprono il vuoto politico, quando l’individualismo rompe i legami collettivi? Che cosa succede nel momento in cui l’elenco dei diritti “di nuova generazione” si allunga sempre di più e la loro efficacia progressivamente svanisce? Che cosa accade quando la “società del welfare” diventa un ricordo in bianco e nero? Trionferà il mercato come dimensione unificante? Un variegato mondo associativo, solidale e no profit non si arrende, muovendosi ostinatamente in direzione contraria. Associazioni, Ong, forum sociali e reti di volontariato costituiscono una realtà affascinante, a volte vischiosa, comunque mai banale. Questo libro ne disegna i contorni: che cosa è, per quali obiettivi lotta e quali risultati ha ottenuto la solidarietà in Italia

Modeling, interoperable simulation and serious games as an innovative approach for disaster relief

This paper presents the use of Human Behavior Modeling for Disaster Relief and Emergency Management. The authors propose an innovative MS2G (Modeling, Interoperable Simulation and Serious Game) using Intelligent Agents to reproduce a complex scenario used for Verification, Validation and Accreditation of the approach. The case study is inspired to South Sudan situation and to the necessity to provide accommodations, food, health care services, security and administrative support to a large number of IDPs (Internally Displaced Persons) over a wide area. The simulator includes camp preparation and installation, air drops, logistics network creation while the model includes populations, entities and units as well as different equipment (e.g. cargo planes, helicopters, ground units, etc.)

"ASTEROID: a new 64 channel ASIC for source follower based readout of the MIXS DEPFET arrays on BepiColombo"

ASTEROID is a new 64 channel ASIC developed to read out a DEPFET macropixel array. This sensor will be part of the MIXS instrument that will be used in the ESA's BepiColombo Mercury exploration mission. The detector will operate in an environment with high density of solar proton flux that will cause severe radiation damage and an increase of leakage current during mission lifetime. Given the relatively high value of the leakage current, a high speed readout and a proper cooling of the detector is needed in order to achieve the required energy resolution. The contribution of the readout electronics to the noise should be smaller than 10 electrons r.m.s. The foreseen pixel arrays are optimized for source follower readout. In this operating mode of the DEPFETs, the readout electronics is AC-coupled. This allows easy coping with non homogeneity of the pixel matrix and - most of all - an easy compensation of threshold voltage shifts of the DEPFET devices due to radiation damage. In order to achieve the low noise value required at short processing time, ASTEROID implements a trapezoidal weighting function, which represents the time-limited optimum filter for white series noise. This is the major electronics noise source at the foreseen readout speed. Measurements on a first prototype of the ASIC have shown the very satisfactory resolution of 147 eV on Mn-K alpha peak of Fe-55 with a readout time of approximately 1.2 mu s, that would lead, considering the settling time of the DEPFET, to a total processing time of 4.2 mu s. We present the experimental results of a first prototype that includes 4 analog channels and a new digital section for the generation of the timing signals of the circuit. This digital section is based on radiation-hardened dual-port memory cells and registers and has already been implemented to serve all the 64 channels foreseen for the final version of the ASIC

The IXO Wide-Field Imager

The Wide Field Imager (WFI) of the International X-ray Observatory (IXO) is an X-ray imaging spectrometer based on a large monolithic DePFET (Depleted P-channel Field Effect Transistor) Active Pixel Sensor. Filling an area of 10 × 10 cm with a format of 1024 × 1024 pixels it will cover a field of view of 18 arcmin. The pixel size of 100 × 100 mu m corresponds to a fivefold oversampling of the telescope's expected 5 arcsec point spread function. The WFI's basic DePFET structure combines the functionalities of sensor and integrated amplifier with nearly Fano-limited energy resolution and high efficiency from 100 eV to 15 keV. The development of dedicated control and amplifier ASICs allows for high frame rates up to 1 kHz and flexible readout modes. Results obtained with representative prototypes with a format of 256 × 256 pixels are presented

The Wide-Field Imager for IXO: Status and future activities

The Wide Field Imager (WFI) of the International X-ray Observatory (IXO) is an X-ray imaging spectrometer based on a large monolithic DePFET (Depleted P-channel Field Effect Transistor) Active Pixel Sensor. Filling an area of 10 x 10 cm2 with a format of 1024 x 1024 pixels it will cover a field of view of 18 arcmin. The pixel size of 100 x 100 μm2 corresponds to a fivefold oversampling of the telescope's expected 5 arcsec point spread function. The WFI's basic DePFET structure combines the functionalities of sensor and integrated amplifier with nearly Fano-limited energy resolution and high efficiency from 100 eV to 15 keV. The development of dedicated control and amplifier ASICs allows for high frame rates up to 1 kHz and flexible readout modes. Results obtained with representative prototypes with a format of 256 x 256 pixels are presented