A successful experimental model for intimal hyperplasia prevention using a resveratrol eluting balloon

Objective: Restenosis due to intimal hyperplasia is a major clinical problem that compromises the success of angioplasty and endovascular surgery. Resveratrol (RSV) has demonstrated a beneficial effect on restenosis from angioplasty. Unfortunately, the physicochemical characteristics of RSV reduce the practicality of its immediate clinical application. This work proposes an experimental model aiming to setup an intravessel, elutable, RSV-containing compound. Methods: A 140 mg/mL RSV sterile injectable solution with a suitable viscosity for intravascular administration by drugdelivery catheter (RSV-c) was prepared. This solution was locally administered in the common iliac artery of adult male New Zealand White rabbits using a dedicated device (Genie; Acrostak, Geneva, Switzerland) after the induction of intimal hyperplasia by traumatic angioplasty. The RSV concentrations in the wall artery were determined, and the thickness of the harvested iliac arteries was measured over a 1-month period. Results: The Genie catheter was applied in rabbit vessels, and the local delivery resulted in an effective reduction in restenosis after plain angioplasty. Notably, RSV-c forced into the artery wall by balloon expansion might accumulate in the interstitial areas or within cells, avoiding the washout of solutions. Magnification micrographs showed intimal proliferation was significantly inhibited when RSV-c was applied. Moreover, no adverse events were documented in in vitro or in vivo studies. Conclusions: RSV can be advantageously administered in the arterial walls by a drug-delivery catheter to reduce the risk of restenosis

FAVOR (FAst Variability Optical Registration) -- A Two-telescope Complex for Detection and Investigation of Short Optical Transients

An astronomical complex intended to detect optical transients (OTs) in a wide field and follow them up with high time resolution investigation is described.Comment: 4 pages, 3 figures. To be published in "Il Nuovo Cimento", Proceedings of the 4th Rome Workshop on Gamma-Ray Bursts in the Afterglow Era, eds. L. Piro, L. Amati, S. Covino, B. Gendr

Diagnosis and treatment of acute pancreatitis: The position statement of the Italian Association for the study of the pancreas

BACKGROUND AND AIM: Till now, no Italian studies providing information on acute pancreatitis have been published. The aim of this study was to evaluate the epidemiological and clinical characteristics of acute pancreatitis in Italy. MATERIALS AND METHODS: The study involved 37 Italian centres distributed homogeneously throughout the entire national territory and prospectively collected epidemiological, anamnestic, laboratory, radiological, therapeutic (pharmacological, endoscopic and surgical) data, relevant to each individual case of acute pancreatitis consecutively observed during the period from September 1996 to June 2000. RESULTS: One thousand two hundred and six case report forms were collected, but 201 patients (16.6%) were subsequently eliminated from the final analysis. We therefore studied 1005 patients, 533 (53%) males and 472 (47%) females, mean age 59.6 +/- 20 years. On the basis of the Atlanta classification of acute pancreatitis, 753 patients of the 1005 cases analysed (75%) were mild and 252 patients (25%) severe. The aetiology was biliary in 60% of the patients, related to alcohol abuse in 8.5%, while in 21% of the cases it could not be identified. Over 80% of the patients (83%) were admitted to hospital within 24 h from the onset of clinical symptoms, while only 6% were admitted after 48 h. In particular, 65% of the patients were admitted to hospital within the first 12 h. Antibiotics were used in 85% of the severe and 75% of mild forms. Endoscopic therapy was carried out in 65% of the severe cases, but only in 40% it was carried out prior to 72 h. Eighty-five patients (8.5% of the total, 34% of the severe forms) underwent surgical intervention: 20% on the first day, 38.5% within the fourth day, and the remaining (41.5% of the cases) later on for infected necrosis. The mean duration of hospitalisation for patients with mild pancreatitis was 13 +/- 8 days, while for the severe disease it was of 30 +/- 14 days. The overall mortality rate was 5%, 17% in severe and 1.5% in mild pancreatitis. CONCLUSIONS: Acute pancreatitis in Italy is more commonly a mild disease with a biliary aetiology. The treatment of the disease is not optimal and, on the basis of these data, needs to be standardised. Despite this, the overall mortality rate is low (5%BACKGROUND AND AIM: Till now, no Italian studies providing information on acute pancreatitis have been published. The aim of this study was to evaluate the epidemiological and clinical characteristics of acute pancreatitis in Italy. MATERIALS AND METHODS: The study involved 37 Italian centres distributed homogeneously throughout the entire national territory and prospectively collected epidemiological, anamnestic, laboratory, radiological, therapeutic (pharmacological, endoscopic and surgical) data, relevant to each individual case of acute pancreatitis consecutively observed during the period from September 1996 to June 2000. RESULTS: One thousand two hundred and six case report forms were collected, but 201 patients (16.6%) were subsequently eliminated from the final analysis. We therefore studied 1005 patients, 533 (53%) males and 472 (47%) females, mean age 59.6 +/- 20 years. On the basis of the Atlanta classification of acute pancreatitis, 753 patients of the 10

A flash in the dark: UVES/VLT high resolution spectroscopy of GRB afterglows

We present the first high resolution (R=20000--45000, corresponding to 14 km/s at 4200A to 6.6 km/s at 9000A) observations of the optical afterglow of Gamma Ray Bursts. GRB020813 and GRB021004 were observed by UVES@VLT 22.19 hours and 13.52 hours after the trigger, respectively. These spectra show that the inter--stellar matter of the GRB host galaxies is complex, with many components contributing to each main absorption system, and spanning a total velocity range of up to about 3000 km/s. Several narrow components are resolved down to a width of a few tens of km/s. In the case of GRB021004 we detected both low and high ionization lines. Combined with photoionization results obtained with CLOUDY, the ionization parameters of the various systems are consistent with a remarkably narrow range with no clear trend with system velocity. This can be interpreted as due to density fluctuations on top of a regular R^-2 wind density profile.Comment: Most figure improved, a few typos corrected, added a new subsection. ApJ in pres

Integral results on GRB030320: a long gamma-ray burst detected at the edge of the field of view

GRB030320 is the 5th Gamma-ray burst (GRB) detected by INTEGRAL in the field of view (FoV). It is so far the GRB with the largest off-axis angle with respect to the INTEGRAL pointing direction, near to the edge of the FoV of both main instruments, IBIS and SPI. Nevertheless, it was possible to determine its position and to extract spectra and fluxes. The GRB nature of the event was confirmed by an IPN triangulation. It is a ~ 60 s long GRB with two prominent peaks separated by ~ 35 s. The spectral shape of the GRB is best represented by a single power law with a photon index Gamma ~ 1.7. The peak flux in the 20 - 200 keV band is determined to ~ 5.7 photons cm-2 s-1 and the GRB fluence to 1.1 x 10-5 erg cm-2. Analysing the spectral evolution of the GRB, a ``hard-to-soft'' behaviour emerges. A search for an optical counterpart has been carried out, but none was found.Comment: 5 pages, 3 figures. Accepted for publication in A&AL (INTEGRAL issue

Stabilization of linear carbon structures in a solid Ag nanoparticle assembly

Linear sp carbon nanostructures are gathering interest for the physical properties of one-dimensional (1D) systems. At present, the main obstacle to the synthesis and study of these systems is their instability. Here we present a simple method to obtain a solid system where linear sp chains (i.e. polyynes) in a silver nanoparticle assembly display a long term stability at ambient conditions. The presence and the behavior of linear carbon is investigated by Surface Enhanced Raman Scattering (SERS) exploiting the plasmon resonance of the silver nanoparticles assembly. This model system opens the possibility to investigate an intriguing form of carbon nanostructures

Metformin and Everolimus: A Promising Combination for Neuroendocrine Tumors Treatment

Introduction: Treatment options for neuroendocrine tumors (NETs) are rarely curative, as NETs frequently show resistance to medical therapy. The use of everolimus, an mTOR inhibitor, is limited by the development of resistance, probably due to the activation of Akt signaling. In this context, the antidiabetic drug metformin is able to inhibit mTOR, providing a rationale for the use of metformin and everolimus in combination. Methods: We investigated the effects of the metformin and everolimus combination on NET cell proliferation, apoptosis, colony formation, cell viability, NET spheroids growth and the involvement of the Akt and mTOR pathways, and also developed everolimus-resistant NET cells to further study this combination. Results: Metformin and everolimus in combination are more effective than monotherapy in inhibiting pancreatic NET (PAN-NET) cell proliferation (-71% \ub1 13%, p < 0.0001 vs. basal), whereas no additive effects were observed on pulmonary neuroendocrine tumor (PNT) cell proliferation. The combinatorial treatment is more effective than monotherapy in inhibiting colony formation, cell viability, NET spheroids growth rate and mTOR phosphorylation in both NET cell lines. In a PAN-NET cell line, metformin did not affect Akt phosphorylation; conversely, it significantly decreased Akt phosphorylation in a PNT cell line. Using everolimus-resistant NET cells, we confirmed that metformin maintained its effects, acting by two different pathways: Akt-dependent or independent, depending on the cell type, with both leading to mTOR suppression. Conclusions: Considering the promising effects of the everolimus and metformin combination in NET cells, our results provide a rationale for its use in NET patients

Planetary companions around the metal-poor star HIP 11952

Aims. We carried out a radial-velocity survey to search for planets around metal-poor stars. In this paper we report the discovery of two planets around HIP 11952, a metal-poor star with [Fe/H]= -1.9 that belongs to our target sample. Methods. Radial velocity variations of HIP 11952 were monitored systematically with FEROS at the 2.2 m telescope located at the ESO La Silla observatory from August 2009 until January 2011. We used a cross-correlation technique to measure the stellar radial velocities (RV). Results. We detected a long-period RV variation of 290 d and a short-period one of 6.95 d. The spectroscopic analysis of the stellar activity reveals a stellar rotation period of 4.8 d. The Hipparcos photometry data shows intra-day variabilities, which give evidence for stellar pulsations. Based on our analysis, the observed RV variations are most likely caused by the presence of unseen planetary companions. Assuming a primary mass of 0.83 M\odot, we computed minimum planetary masses of 0.78 MJup for the inner and 2.93 MJup for the outer planet. The semi-major axes are a1 = 0.07 AU and a2 = 0.81 AU, respectively. Conclusions. HIP 11952 is one of very few stars with [Fe/H]< -1.0 which have planetary companions. This discovery is important to understand planet formation around metal-poor starsComment: Published in A&

GRB 070311: a direct link between the prompt emission and the afterglow

We present prompt gamma-ray, early NIR/optical, late optical and X-ray observations of the peculiar GRB 070311 discovered by INTEGRAL, in order to gain clues on the mechanisms responsible for the prompt gamma-ray pulse as well as for the early and late multi-band afterglow of GRB 070311. We fitted with empirical functions the gamma-ray and optical light curves and scaled the result to the late time X-rays. The H-band light curve taken by REM shows two pulses peaking 80 and 140 s after the peak of the gamma-ray burst and possibly accompanied by a faint gamma-ray tail. Remarkably, the late optical and X-ray afterglow underwent a major rebrightening between 3x10^4 and 2x10^5 s after the burst with an X-ray fluence comparable with that of the prompt emission extrapolated in the same band. Notably, the time profile of the late rebrightening can be described as the combination of a time-rescaled version of the prompt gamma-ray pulse and an underlying power law. This result supports a common origin for both prompt and late X-ray/optical afterglow rebrightening of GRB 070311 within the external shock scenario. The main fireball would be responsible for the prompt emission, while a second shell would produce the rebrightening when impacting the leading blastwave in a refreshed shock (abridged).Comment: 14 pages, 11 figures, 4 tables, accepted to A&

External validation of three lymph node ratio-based nomograms predicting survival using an international cohort of patients with resected pancreatic head ductal adenocarcinoma.

INTRODUCTION Lymph node ratio (LNR) is an important prognostic factor of survival in patients with pancreatic ductal adenocarcinoma (PDAC). This study aimed to validate three LNR-based nomograms using an international cohort. MATERIALS AND METHODS Consecutive PDAC patients who underwent upfront pancreatoduodenectomy from six centers (Europe/USA) were collected (2000-2017). Patients with metastases, R2 resection, missing LNR data, and who died within 90 postoperative days were excluded. The updated Amsterdam nomogram, the nomogram by Pu et al., and the nomogram by Li et al. were selected. For the validation, calibration, discrimination capacity, and clinical utility were assessed. RESULTS After exclusion of 176 patients, 1'113 patients were included. Median overall survival (OS) of the cohort was 23 months (95% CI: 21-25). For the three nomograms, Kaplan-Meier curves showed significant OS diminution with increasing scores (p < 0.01). All nomograms showed good calibration (non-significant Hosmer-Lemeshow tests). For the Amsterdam nomogram, area under the ROC curve (AUROC) for 3-year OS was 0.64 and 0.67 for 5-year OS. Sensitivity and specificity for 3-year OS prediction were 65% and 59%. Regarding the nomogram by Pu et al., AUROC for 3- and 5-year OS were 0.66 and 0.70. Sensitivity and specificity for 3-year OS prediction were 68% and 53%. For the Li nomogram, AUROC for 3- and 5-year OS were 0.67 and 0.71, while sensitivity and specificity for 3-year OS prediction were 63% and 60%. CONCLUSION The three nomograms were validated using an international cohort. Those nomograms can be used in clinical practice to evaluate survival after pancreatoduodenectomy for PDAC