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Background Several reports demonstrated a strong association between the level of adherence to the protocol and improved clinical outcomes after surgery. However, it is difficult to obtain full adherence to the protocol into clinical practice and has still not been identified the threshold beyond which improved functional results can be reached. Methods The ERCOLE (ERas and COLorectal Endoscopic surgery) study was as a cohort, prospective, multi-centre national study evaluating the association between adherence to ERAS items and clinical outcomes after minimally invasive colorectal surgery. The primary endpoint was to associate the percentage of ERAS adherence to functional recovery after minimally invasive colorectal cancer surgery. The secondary endpoints of the study was to validate safety of the ERAS programme evaluating complications’ occurrence according to Clavien-Dindo classification and to evaluate the compliance of the Italian surgeons to each ERAS item. Results 1138 patients were included. Adherence to the ERAS protocol was full only in 101 patients (8.9%), > 75% of the ERAS items in 736 (64.7%) and > 50% in 1127 (99%). Adherence to > 75% was associated with a better functional recovery with 90.2 ± 98.8 vs 95.9 ± 33.4 h (p = 0.003). At difference, full adherence to the ERAS components 91.7 ± 22.1 vs 92.2 ± 31.6 h (p = 0.8) was not associated with better recovery. Conclusions Our results were encouraging to affirm that adherence to the ERAS program up to 75% could be considered satisfactory to get the goal. Our study could be considered a call to simplify the ERAS protocol facilitating its penetrance into clinical practice.

Cockayne syndrome (CS) is a rare genetic disorder caused by mutations (dysfunction) in CSA and CSB. CS patients exhibit mild photosensitivity and severe neurological problems. Currently, CS diagnosis is based on the inefficiency of CS cells to recover RNA synthesis upon genotoxic (UV) stress. Indeed, upon genotoxic stress, ATF3, an immediate early gene is activated to repress up to 5000 genes encompassing its responsive element for a short period of time. On the contrary in CS cells, CSA and CSB dysfunction impairs the degradation of the chromatin-bound ATF3, leading to a permanent transcriptional arrest as observed by immunofluorescence and ChIP followed by RT-PCR. We analysed ChIP-seq of Pol II and ATF3 promoter occupation analysis and RNA sequencing-based gene expression profiling in CS cells, as well as performed immunofluorescence study of ATF3 protein stability and quantitative RT-PCR screening in 64 patient cell lines. We show that the analysis of few amount (as for example CDK5RAP2, NIPBL and NRG1) of ATF3 dependent genes, could serve as prominent molecular markers to discriminate between CS and non-CS patient’s cells. Such assay can significantly simplify the timing and the complexity of the CS diagnostic procedure in comparison to the currently available methods.

International audience; Cytokinesis is monitored by a molecular machinery that promotes the degradation of the intercellular bridge, a transient protein structure connecting the two daughter cells. Here, we found that CSA and CSB, primarily defined as DNA repair factors, are located at the midbody, a transient structure in the middle of the intercellular bridge, where they recruit CUL4 and MDM2 ubiquitin ligases and the proteasome. As a part of this molecular machinery, CSA and CSB contribute to the ubiquitination and the degradation of proteins such as PRC1, the Protein Regulator of Cytokinesis, to ensure the correct separation of the two daughter cells. Defects in CSA or CSB result in perturbation of the abscission leading to the formation of long intercellular bridges and multinucleated cells, which might explain part of the Cockayne syndrome phenotypes. Our results enlighten the role played by CSA and CSB as part of a ubiquitin/proteasome degradation process involved in transcription, DNA repair, and cell division.

Introduction. In the last years many mini-invasive approaches were developed in order to reduce postoperative pain and complication after haemorrhoid surgery: one of these alternatives is represented by Hemorpex System, a relatively young technique that combines transanal dearterialization with mucopexy through a dedicated proctoscope. Case Presentation. A 78-year-old male patient was admitted to the Emergency Department for acute urinary retention and elevated temperature. Hemorpex procedure was performed 4 years before. Clinical, endoscopic, and radiological findings demonstrated the presence of multiple diverticula-like structures fulfilled by purulent fluid and a deep alteration of the normal anatomy of the rectum. He was treated following the standard protocol of acute diverticulitis and full recovery from symptoms was achieved. Discussion. Hemorpex System is a young technique, and nowadays-available studies lack long-term follow-up data. Anatomical changes induced by the procedure are consistent and definitive. Our patient luckily demonstrated a prompt response to conservative treatment, but it must be taken into account that, in case of medical treatment failure, surgical approach would be necessary and the actual patient anatomical changes could lead the surgeon to unavoidable threatening maneuvers.

Background Liver transplantation is the best treatment for end-stage liver disease. The interruption of the blood supply to the donor liver during cold storage damages the liver, affecting how well the liver will function after transplant. The drug Simvastatin may help to protect donor livers against this damage and improve outcomes for transplant recipients. The aim of this study is to evaluate the benefits of treating the donor liver with Simvastatin compared with the standard transplant procedure. Patient and methods We propose a prospective, double-blinded, randomized phase 2 study of 2 parallel groups of eligible adult patients. We will compare 3-month, 6-month, and 12-month graft survival after LT, in order to identify a significant relation between the two homogenous groups of LT patients. The two groups only differ by the Simvastatin or placebo administration regimen while following the same procedure, with identical surgical instruments, and medical and nursing skilled staff. To reach these goals, we determined that we needed to recruit 106 patients. This sample size achieves 90% power to detect a difference of 14.6% between the two groups survival using a one-sided binomial test. Discussion This trial is designed to confirm the effectiveness of Simvastatin to protect healthy and steatotic livers undergoing cold storage and warm reperfusion before transplantation and to evaluate if the addition of Simvastatin translates into improved graft outcomes. Trial registration ISRCTN27083228.

Background We determined the range of normal spleen dimensions evaluated by ultrasonography (US) in children according to sex and age and the relationship between splenic measurements, auxological data and body proportions, in order to define splenomegaly parameters in support of the surgical mini-invasive approaches in pediatrics. Methods We prospectively examined 317 caucasian children of both sexes. The patients were divided into three groups: 0–3 years; 4–10 years; 11–18 years. Sex, weight, height/length, body mass index (BMI), waist circumference and xipho-pubic distance were determined for each child. US spleen evaluation included longitudinal/antero-posterior/transverse diameters, transverse area and volume. Spleen volume/abdominal volume, longitudinal spleen diameter/longitudinal left kidney diameter and longitudinal spleen diameter/xipho-pubic distance ratios were also calculated. Results For caucasian subjects, in different age groups spleen volume, transverse area and diameter increased while the spleen/abdominal volume ratio decreased significantly (p

Ceres is the largest body of the Main Belt, which is characterized by a huge abundance of water ice in its interior. This feature is suggested by its relatively low bulk density (2162 kg m-3, Russell et al. 2016, Park et al. 2016) and by several geological and geochemical evidences (specific minerals or salts produced by acqueous alteration, icy patches on the surface, lobate morphologies interpretable as surface flows (De Sanctis et al. 2016, Carrozzo et al. 2018, Raponi et al. 2018, Zolotov 2017 and Schmidt et al., 2017).Ceres is partially differentiated as suggested by its normalized moment of inertia, 0.37 (Park et al. 2016). A typical internal structure proposed for Ceres is: a rocky core (300-350 km), an icy (or muddy) mantle (100-150 km) and a rocky crust some kilometers in depth (eg. Mc Cord & Sotin 2005, Neveu & Desch, 2015). The temperature gradient across the mantle, estimated through numerical modelling (e.g. McCord & Sotin 2005, Neveu & Desch 2015) would be large enough to initiate a thermal convection in the mantle. Since the mantle is not uniquely defined from a composition point of view, in this work we explore how the composition and, in particular the "degree" of muddiness of the mantle, can influence the characteristic of thermal convection. We also estimate the thickness of the top conductive boundary layer and the mechanical stress, which can cause its deformation. - De Sanctis, M., et al. (2015) doi:10.1038/nature16172.- Russell, C., et al. (2016), doi:10.1126/science.aaf4219.- Park, R., et al. (2016),Lunar and Planetary Science Conference, vol. 47, p. 1781.- Schmidt, B. E., et al. (2017), doi:doi:10.1038/ngeo2936- Zolotov, M. Y. (2017), doi:https://doi.org/10.1016 j.icarus.2017.06.018.- Carrozzo, F., et al. (2018), Nature, formation and distribution of carbonates on ceres, Science Advances.- Raponi, A., et al. (2018), Variations in the amount of water ice on ceres' surface suggest a seasonal water cycle, Science Advances.- McCord, T., and C. Sotin (2005), doi:10.1029/2004JE002244.- Neveu, M., and S. Desch (2015), Geochemistry, thermal evolution, and cryovolcanism on Ceres with a muddy ice mantle, Geophys. Res. Lett.

Core dynamo is one of the most efficient mechanism to produce magnetic field in the planetary bodies as well as in the minor bodies of the solar system. It is interesting to study and to evaluate how the thickness and composition of the overlying rocky lid influences the thermal convective evolution of the core.

Ceres is a particular object of the solar system, since it is a "transition body" between the icy satellites of the outer solar system and the rocky bodies of the inner part. Probably it is differentiated [1,2], i.e. it has a core made of "rock" (silicates) with a weak presence of metals, a large icy mantle and a rocky crust. In particular, it has been proposed the existence on the surface of the ammoniated phyllosilicates, compatible with an outer solar system origin [3]. Also water in clay minerals, brucite, and iron-rich serpentine have been proposed to exist on the surface [4]. Ice directly on the surface regolith seems to be very unstable: numerical simulations of [5] indicate that it can last for very few orbits. A crust made of a mixture of ice and rock is potentially unstable. In the solar system, for example, Callisto has such a crust but its surface temperature is below the critical temperature for the Rayleigh-Taylor instability [6]: this seems not to be the case of Ceres. In this work, we verify the stability of the primordial crust, by assuming a certain initial composition (ice and rock) and thickness. We assume a post-differentiation Ceres, made of three layers (rocky core, icy mantle and crust). The key role is played by the viscosity of the layers, which influenced the survival or not of the primordial crust. We applied the method of the parametrized thermal convection widely diffused in literature. [1] McCord, T.B. and Sotin, C., 2005, JGR 110 [2] Castillo-Rogez, J.C., and McCord, T.B., 2010, Icarus 205, 443-459 [3] De Sanctis, M.C. et al., 2015, doi:10.1038/nature16172 [4] Rivkin, A.S., et al., 2014, Space Sci Rev, 95-116, 163, doi 10.1007/s11214-010-9677-4 [5] Formisano, M., et al., 2016, MRAS 455, 1892-1904 [6] Shoji, D. and Kurita, K., 2014, doi:10.1002/2014JE004695.

Recently, a study on the magnetization of the eucrite meteorite Allan Hills A81001 [1] has suggested the possibility that, in its primordial history, Vesta had an active core dynamo. The magnetic field associated could have preserved Vesta from the space-weathering. In this work, using a parametrized thermal convection method, we verified the thermophysical conditions for the onset of a core dynamo. The starting point is a post-differentiated structure [2,3,4], made of a metallic core, silicate mantle and rocky crust. We explored four different fully differentiated configurations of Vesta [5], characterized by different chondritic composition, with the constraints on the core size and density provided by [6]. We also explored three different scaling laws for the core velocity (mixing-length theory, MAC and an intermediate case). Core and mantle have both a temperature-dependent viscosity, which is the parameter that largely influences the magnetic Reynolds number and the dynamo duration. Our results suggest that Vesta had an active dynamo, whose duration lies in the range 150-500 Myr and the more appropriate scaling law for the core velocity is that given by the mixing-length theory. The maximum strength of the primordial core magnetic field is compatible with the estimations provided by [1]. [1] Fu, R. et al, 2012, Science 338, 238 [2] Ghosh, A. and McSween, H.Y., 1998, Icarus, 134, 187 [3] Formisano, M. et al., 2013, Meteoritics and Planetary Science, 48, 2316 [4] Neumann, W., et al., 2014, Earth and Planetary Science Letters, 395, 267 [5] Toplis, M.J., et al., 2013, Meteoritics and Planetary Science, 48, 2300 [6] Ermakov, A.I., et al.2014, Icarus, 240, 146

Prenatal surgery represents a multifactorial stressor event for mother and fetus. The stress response to fetal surgery was evaluated by measuring maternal plasma and amniotic fluid (AF) cortisol levels in the myelomeningocele (MMC) sheep model.Pregnant ewes (n = 8) underwent general anesthesia for MMC-induction (step 1: 75 d gestation), surgical defect repair (step 2: 110 d gestation), and delivery (step 3: 140 d gestation). Maternal blood samples were taken before surgery (surgical stage T1), after laparotomy and uterine exposure (surgical stage T2), at the end of the procedure (surgical stage T3). Fetal stress was evaluated by measuring cortisol levels in AF after hysterotomy at steps 1-3.Maternal cortisol concentrations at T2 and T3 increased compared with T1 (p = 0.019 and p = 0.046). AF cortisol response increased from 1 to 3 surgical steps and during pregnancy. The AF cortisol level was lower than maternal serum levels (induction p 0.001; repair p 0.001; caesarean section p 0.001).Hysterotomy was the most stressful event in the ewes. Fetuses seemed to be partially protected from the high maternal cortisol levels. The fetal stress response to prenatal surgery increased with gestational age. Pain perception development, fetal maturation, and "pain memory" are probably associated with this increase.

The design, realization and test of a tri-band concurrent Doherty power amplifier (DPA) is presented. The prototype has been realized in hybrid technology using GaN HEMT devices. The operating bands have been selected around the following carrier frequencies f 1 = 1.84GHz, f 2 = 2.14GHz and f 3 = 2.65GHz corresponding to LTE, UMTS and WiMax applications, respectively. The prototype has been tested and successfully linearized with a 10-MHz LTE signal at f 1 and a 10-MHz two carriers WCDMA signals at f 2 and f 3 , showing promising results.

Objective Mesenchymal stromal cells (MSCs) expanded in vitro have been proposed as a potential therapy for congenital or acquired skin defects in pediatrics. The aim of this pre-clinical study was to investigate the effects of intradermal injections of MSC in experimental cutaneous wound repair comparing allogeneic and autologous adipose stem cells (ASCs) and autologous bone marrow-mesenchymal stromal cells (BM-MSCs). Methods Mesenchymal stromal cells were in vitro expanded from adipose and BM tissues of young female New Zealand rabbits. MSCs were characterized for plastic adhesion, surface markers, proliferation and differentiation capacity. When an adequate number of cells (ASCs 10 × 106 and BM-MSCs 3 × 106, because of their low rate of proliferation) was reached, two skin wounds were surgically induced in each animal. The first was topically treated with cell infusions, the second was used as a control. The intradermal inoculation included autologous or allogeneic ASCs or autologous BM-MSCs. For histological examination, animals were sacrificed and wounds were harvested after 11 and 21 days of treatment. Results Rabbit ASCs were isolated and expanded in vitro with relative abundance, cells expressed typical surface markers (CD49e, CD90 and CD29). Topically, ASC inoculation provided more rapid wound healing than BM-MSCs and controls. Improved re-epithelization, reduced inflammatory infiltration and increased collagen deposition were observed in biopsies from wounds treated with ASCs, with the best result in the autologous setting. ASCs also improved restoration of skin architecture during wound healing. Conclusion The use of ASCs may offer a promising solution to treat extended wounds. Pre-clinical studies are however necessary to validate the best skin regeneration technique, which could be used in pediatric surgical translational research.

Background: The main hydrosoluble metabolites in three different human congenital pulmonary malformations are described by nuclear magnetic resonance (NMR) spectroscopy.Methods: Bronchogenic cyst (BC), congenital lobar emphysema (CLE) and intrapulmonary sequestration (IPS), were analyzed with respect to a control sample. The extracted metabolites were submitted to high-resolution 1H NMR-spectroscopy.Results: Congenital lung malformations showed free choline, phosphocoline and myoinositol high levels. IPS and CLE were found increased in lactic acid/glucose ratio. Lactic acid and glucose values resulted to be more elevated in control sample.Conclusions: Congenital lung lesions showed different metabolomic profiles useful for early diagnosis.

The Mt. Pollino Fault Zone is located in the northern sector of the Calabria region (southern Italy). It represents a segment between the southernmost part of the Apennines and the Calabrian Arc. In the Pollino area, seismic events of magnitude > 5 are not currently reported in literature and within the seismic catalogues, therefore this ―gap‖ zone has been defined ―silent‖. Due to the geomorphological, geological and paleoseismological evidences of Quaternary faulting, the Pollino-Castrovillari faults are considered active, as demonstrated also by some recent reactivations, that have generated several earthquakes of moderate magnitude (Mmax ≤ 5.0) in a north-western sector, near Mormanno (Mercure Basin) and Morano villages (Morano-Castrovillari Basin). Therefore, the studied area retains many uncertainties in the definition of the seismic hazard. With these premises an integrated project started in 2012 (Agreement INGV-DPC 2012-2013, Project S1) aims to improve the base-knowledge for assessing the seismogenic potential. Among the different geological studies, the project encompasses the GPR fault imaging on several sites, having different goals: 1) define the location and the geologic characteristics of active faults; 2) detect new evidences of ―recent‖ faulting; 3) correctly locate these structural elements on a geologic map; 4) support further paleoseismological surveys. A first 2DGPR survey was done at the Grotta Carbone site, about 4 kilometers from Castrovillari, for which some trench logs were already available, in order to “image” the fault zone and to provide a GPR data calibration using the stratigraphic information. The results of the radargrams interpretation show a characteristic GPR signature of the tectonic structures and faulted units and a different dielectric behavior among the units located across the fault, revealing an excellent matching with the available geological data. Clear tectonic features and their vertical offset between layers have been highlighted within the fault zone. The stratigraphy of the trenches have been extended, along the fault and in depth, providing new useful information essential for a better definition of the seismic hazard of the area and for a future 2D/3D dataset extension across other sites.