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Supplementary Tables S1-S5. Table S1: Antiproliferative effects of PI3K inhibitors on SKMES-1 and PIK3CA amplified/mutated clones Tables S2-S4: densitometric analysis of Western blotting of Figure 1D Table S5: Antiproliferative effects of PI3K inhibitors on H596 and HCC2450 cells

Supplementary Figures S1-S5. Figure S1: p-AKT levels in PIK3CA transfected clones Figure S2: Induction of cell death after treatment with PI3K inhibitors Figure S3: Time course evaluation of PI3K/AKT/mTOR pathway activity after exposure to PI3K inhibitors Figure S4: Evaluation of cell migration after treatment with PI3K inhibitors Figure S5: CD133 expression in tumor spheres

Clinical case 23–year–old male. No medical history Not vaccinated for Sars–Cov2; Recent Sars–Cov2 infection (negative antigenic swab on 03/01/22); Pharyngodynia treated with ibuprofen + ciprofloxacin and amoxicillin ac clavulanic acid(suspended for purpuric lesions on hands) After 5 days from onset of symptoms, access to PS for loss of consciousness. Laboratory: ph 7.4; Lat 3.4 EKG: sinus tachycardia HR 126 bpm ECHOCARDIOGRAM: Non–dilated left ventricle, marked reduction in FE (15%) spontaneous echocontrast in ventricular cavity chest TC: hypodense tissue in anterior mediastinum; adenopathy in peribronchial site, distended gallbladder transfer to Vanvitelli Cardiac ICU Amine support with augmented DBT for hypotension and tachycardia LAB: Tni 2193; Nt proBNP 27796; PCR 26; PCT 4; crea 1,4, Lat 1 CATH DX + EMB after 24 hours EBM: …Mixed cellularity endomyocarditis, predominantly lymphocytic, presence of eosinophils… enrollment in the MYTHS study: placebo group (saline solution) after 10 day MRI:Normal biventricular systolic function. Tissue characterization images consistent with the presence of limited area of active myocardial damage and with nonischemic pattern involving the basal segment of the infero–lateral wall of the left ventricle. Discussion The case has been a source of considerable discussion to establish the etiology of myocarditis. Although with numerous doubts, after careful evaluation of the histologic picture, the case falls under possible MIS–A (MULTISYSTEM INFLAMMATORY SYNDROME in adult) Cardiac manifestations of MIS–A include myocarditis, pericarditis, and arrhythmias, which can rapidly lead to cardiogenic shock.

Purpose To investigate whether eosinophils and other white blood cell subtypes could be used as response and prognostic markers to anti-Programmed cell Death-1 or anti-PD-Ligand-1 treatments in non-small cell lung cancer patients. Methods We retrospectively analyzed data from the NSCLC patients consecutively treated at our hospital with a PD-1/PD-L1 inhibitor in monotherapy for advanced disease. A total of 191 patients were evaluated at three time-points to investigate any relation between tumor response and WBC counts. Results Baseline WBC and subtypes did not differ according to the type of response seen under treatment. A higher relative eosinophil count (REC) correlated with more objective responses (p = 0.019 at t1 and p = 0.014 at t2; OR for progression = 0.54 and 0.53, respectively) independently of the smoking status, PD-L1 status, and immune-related toxicity (IRT). Higher REC was also associated with a longer duration of treatment (p = 0.0096). Baseline absolute neutrophil count was prognostic (p = 0.049). At t1 relative lymphocytes, absolute and relative neutrophils, and neutrophil-to-lymphocyte ratio were prognostic (p = 0.044, p = 0.014, p = 0.0033, and p = 0.029, respectively). Conclusion Our results show that in NSCLC patients anti-PD-1/PD-L1 therapy induces an early increase only in blood eosinophils, more prominent in responding patients and independent of the smoking status, PD-L1 status, and IRT. Eosinophils are also associated with a longer duration of treatment. Furthermore, our data support a prognostic role of neutrophils, lymphocytes, and their ratio for NSCLC patients with advanced disease treated with PD(L)-1 blockade.

In the last few years, growing evidence indicate that gut miocrobiome is linked to irritable bowel syndrome (IBS) and atherosclerotic disorders. The effect on lipid metabolism seems to be one of the potential mechanisms by which gut microbiome might favour the atherosclerotic process. IBS is a functional bowel disorder defined by the presence of recurrent episodes of abdominal pain associated with altered bowel habits. In this retrospective study the effect of a novel nutraceutical compound, namely Triobiotix, on gastrointestinal symptoms in IBS patients has been evaluated. Effects on lipid profile have been also recorded. Triobiotix is a nutraceutical consisting of: maltodextrin; mineralized extract of Lithothamnion; Bioecolians® gluco–oligosaccharides; ferment mix; short–chain fructo–oligosaccharides powder. We analyzed the database of 40 Italian General Practitioners (GPs). A total of 587 patients with IBS and on Triobiotix were identified. Of these, in only 535 patients, a complete first and second control data was available. The primary endpoint of these analysis was to assess whether Triobiotix resulted in a reduction in pain and meteorism, thus resulting in a lesser intensity of the main gastrointestinal symptoms. Secondary endpoints were to look for significative changes in lab values of total cholesterol, triglycerides levels and glycaemia. Treatment with Triobiotix for four weeks resulted in a reduction in the frequency and intensity of bloating, abdominal pain, and tenesmus. Unexpectedly, at the T1 control, mean cholesterol values were significatively reduced compared to the TO evaluation. Triglycerides levels were also significantly decreased (186.37+66.4 vs. 176.13+67.9; p < 0.05). Our analysis showed an unexpected effect of this combination of micronutrients on lipid profile beyond IBS symptoms. However, further studies are needed to confirm this evidence and to evaluate the particular compound responsible of this effect. A goal of LDL–C less of 115mg/dL is desirable for patients at low to moderate CVR, a significative portion of population is far from this target. The discovery of novel micronutrients combinations with cholesterol lowering effects could be of great importance for the management of patients with low–moderate dyslipidaemia.

According to the latest ESC guidelines on CVD prevention (2021) arterial stiffness (AS) still has a role in predicting future CVD risk and defining patients’ CVD risk level. However, significative measurement difficulties make a widespread evaluation of the AS problematic, especially in the ambulatorial outpatient setting. The IMT measurement is no longer recommended in the CVD risk assessment due to lack of standardization in measurement protocol and low power to reclassify patients toward higher CV risk. Understanding the correlation between the structure and function of the large arteries can lead to an optimization of cardiovascular disease prevention strategies. At present, indices of arterial stiffness have not been associated with qualitative morphological characteristics of intima–media complex. The IM GSM is a relatively simple measurement that can be acquired during a carotid color–Doppler ultrasound exam. The aim of this study was to investigate the relationship between indices of arterial stiffness and echogenicity of intima media complex (IM GSM) of the common carotid arteries in subjects with arterial hypertension. In our study population of 421 hypertensive patients, subjects with IM GSM > 30 showed a significantly increased arterial stiffness and LVMI (P < 0.001). A weak positive correlation was found between IM GSM and SBP (r =0.35, P< 0.001), and duration of hypertension (r = 0.31, P < 0.01). Our study suggests that increased stiffness observed in hypertensives is associated with qualitative changes in carotid arterial wall.

Case Report A 42–year–old woman was carried to emergency room lamenting sudden memory loss. Her husband witnessed the onset of the episode. No recent head trauma was reported, blood pressure was under control. Anterograde and retrograde memory loss was present and confirmed by a neurologist. No other neurological signs were elicitable. Blood exams and toxicological analysis were negative. ECG, chest radiography, and cerebral TC showed no abnormalities. At physical examination a carotid bruit could be appreciated. The patient was asymptomatic. Subsequently an eco–colour–Doppler of carotid artery was performed showing a left common and internal carotid artery dissection. The diagnosis of ICA dissection was confirmed with a contrast CT furthermore excluding the coexistence of an aortic dissection. The anterograde amnesia resolved 15 h after the admission. A neurologist confirmed that the patient experimented an episode of transient global amnesia. After a vascular surgery consultation, a conservative treatment was deemed appropriate. After a 6 month follow up the patient didn’t complain of any other neurological symptom or sign. Transient global amnesia (TGA) is characterized by reversible anterograde and retrograde amnesia of sudden onset that resolves spontaneously within 24 h. The pathophysiological mechanisms underlying this puzzling neurological syndrome are yet not completely clarified. Some studies support an ischemic aetiology for TGA and cases of TGA following ICA–stenting or aortic dissection with involvement of the supra–aortic branches are reported in literature, thus supporting the hypothesis that a cause–effect relationship between ischemic pathologies of supra–aortic trunks and TGA might be present. In the case here presented, a Doppler ultrasound of carotid arteries performed in a patient presenting with TGA, asymptomatic for neck pain, led to a diagnosis of ICA dissection. In order to not miss a spontaneous ICA dissection as a rare ethology of TGA, we suggesto perform an eco–colour–Doppler of the epi–aortic vessels in patients affected by such amnesic syndrome.

We compared seven node vaccination strategies in twelve real-world complex networks. The node vaccination strategies are modeled as node removal on networks. We performed node vaccination strategies both removing nodes according to the initial network structure, i.e., non-adaptive approach, and performing partial node rank recalculation after node removal, i.e., semi-adaptive approach. To quantify the efficacy of each vaccination strategy, we used three epidemic spread indicators: the size of the largest connected component, the total number of infected at the end of the epidemic, and the maximum number of simultaneously infected individuals. We show that the best vaccination strategies in the non-adaptive and semi-adaptive approaches are different and that the best strategy also depends on the number of available vaccines. Furthermore, a partial recalculation of the node centrality increases the efficacy of the vaccination strategies up to 80%.

Background Major surgery such as oesophagectomy requires a postoperative stay in intensive care. Painful stimuli lead to sleep disturbance and impairment in quality of life. The aim of this study was to evaluate the effect of psychological counselling and sleep adjuvant measures on postoperative quality of sleep and quality of life. Methods This RCT was performed between January 2013 and October 2015. Patients undergoing oesophagectomy for cancer were randomized into one of four groups receiving: psychological counselling plus sleep adjuvant measures during the ICU stay; psychological counselling alone; sleep adjuvant measures alone during the ICU stay; or standard care. The primary endpoint was impairment in quality of life measured using the European Organisation for Research and Treatment of Cancer C30-QL2 questionnaire between admission for surgery and discharge from hospital. The secondary endpoint was impairment in quality of sleep assessed by means of the Pittsburgh Sleep Quality Index between admission for surgery and hospital discharge. Results The local ethics committee approved the early termination of the study because of relevant changes in the ICU setting. Some 87 patients were randomized and 74 patients were evaluated in the analysis. Psychological counselling reduced the impairment in quality of life (odds ratio 0·23, 95 per cent c.i. 0·09 to 0·61) and in quality of sleep (odds ratio 0·27, 0·10 to 0·73). Conclusion Perioperative psychological support reduces impairment in quality of life and quality of sleep after oesophagectomy. Registration number: NCT01738620 (http://www.clinicaltrials.gov).

Energy consumption is today one of the most relevant issues in operating HPC systems for scientific applications. The use of unconventional computing systems is therefore of great interest for several scientific communities looking for a better tradeoff between time-to-solution and energy-to-solution. In this context, the performance assessment of processors with a high ratio of performance per watt is necessary to understand how to realize energy-efficient computing systems for scientific applications, using this class of processors. Computing On SOC Architecture (COSA) is a three-year project (2015–2017) funded by the Scientific Commission V of the Italian Institute for Nuclear Physics (INFN), which aims to investigate the performance and the total cost of ownership offered by computing systems based on commodity low-power Systems on Chip (SoCs) and high energy-efficient systems based on GP-GPUs. In this work, we present the results of the project analyzing the performance of several scientific applications on several GPU- and SoC-based systems. We also describe the methodology we have used to measure energy performance and the tools we have implemented to monitor the power drained by applications while running.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and its prevalence is similar to 1-2% of the general population, but higher with increasing age and in patients with concomitant heart disease. The Cox-maze III procedure was a groundbreaking development and remains the surgical intervention with the highest cure rate, but due to its technical difficulty alternative techniques have been developed to create the lesions sets. The field is fast moving and there are now multiple energy sources, multiple potential lesion sets and even multiple guidelines addressing the issues surrounding the surgical treatment of AF both for patients undergoing this concomitantly with other cardiac surgical procedures and also as stand-alone procedures either via sternotomy or via videothoracoscopic techniques. The aim of this document is to bring together all major guidelines in this area into one resource for clinicians interested in surgery for AF. Where we felt that guidance was lacking, we also reviewed the evidence and provided summaries in those areas. We conclude that AF surgery is an effective intervention for patients with all types of AF undergoing concomitant cardiac surgery to reduce the incidence of AF, as demonstrated in multiple randomized studies. There is some evidence that this translates into reduced stroke risk, reduced heart failure risk and longer survival. In addition, symptomatic patients with AF may be considered for surgery after failed catheter intervention or even as an alternative to catheter intervention where either catheter ablation is contraindicated or by patient choice.

Although the hypercortisolism-induced impairment of protein homeostasis is object of several studies, a detailed evaluation of the complete amino acid profile of patients with Cushing's syndrome (CS) has never been performed. The aim of the current open transversal controlled study was to evaluate serum and urinary concentrations as well as renal clearance of the complete series of natural amino acids and their relationship with glucose tolerance in patients with Cushing's disease (CD). Twenty patients with CD (10 active and 10 cured) and 20 sex- and age-matched healthy controls entered the study. Measurement of serum and urinary levels of the complete series of natural amino acids was performed in all patients analyzed by cationic exchange high performance liquid cromatography (HPLC) after 2 weeks of a standardized protein intake regimen. The renal clearance (renal excretion rate) of each amino acid was calculated on the basis of the serum and urinary concentrations of creatinine and the specific amino acid. Fasting glucose and insulin levels, glucose and insulin response to standard glucose load, insulinogenic and homeostasis model insulin resistance (Homa-R) indexes were also evaluated and correlated to the circulating levels and renal clearances of each amino acid. Significantly higher serum (p

The purpose of this case-control study was to evaluate the impact of hybrid minimally invasive esophagectomy for cancer on surgical stress response and nutritional status. All 34 consecutive patients undergoing hybrid minimally invasive esophagectomy for cancer at our surgical unit between 2008 and 2013 were retrospectively compared with 34 patients undergoing esophagectomy with open gastric tubulization (open), matched for neoadjuvant therapy, pathological stage, gender and age. Demographic data, tumor features and postoperative course (including quality of life and systemic inflammatory and nutritional status) were compared. Postoperative course was similar in terms of complication rate. Length of stay in intensive care unit was shorter in patients undergoing hybrid minimally invasive esophagectomy (P = 0.002). In the first postoperative day, patients undergoing hybrid minimally invasive esophagectomy had lower C-reactive protein levels (P = 0.001) and white cell blood count (P = 0.05), and higher albumin serum level (P = 0.001). In this group, albumin remained higher also at third (P = 0.06) and seventh (P = 0.008) postoperative day, and C-reactive protein resulted lower at third post day (P = 0.04). Hybrid minimally invasive esophagectomy significantly improved the systemic inflammatory and catabolic response to surgical trauma, contributing to a shorter length of stay in intensive care unit.

In the management of paroxysmal, drug-refractory atrial fibrillation, pulmonary vein isolation has become a widely accepted treatment option. Currently, the arrhythmias following any form of myocardial ablation are not considered within a period of three months, known as “the blanking period”. Although this period is authority- rather than evidence-based, it has become universally recognized. Indeed, several mechanisms play a role to determine the transient increased risk of post-procedural atrial tachyarrhythmias, occurring early after the procedure. Acute inflammatory changes may be responsible for immediate recurrence, since application of ablative energy on atrial tissue has a pro-inflammatory- and potentially arrhythmogenic effect. Atrial arrhythmias within the first 3 months after ablation are very common (35% to 65% of cases) and their significance as predictor of late recurrences is more significant during the first month. Furthermore, the current biological evidences indicate that the edema of the surrounding and ablated tissue is no longer present after 1 month. In our letter we advocate the reasons why a blanking period of four weeks should appear more reasonable, fostering its clinical importance and utility.

Our study aimed to identify the best prognostic score for fitness for surgery and postoperative morbidity in elderly patients. A prospectively collected database of a consecutive series of patients with esophageal cancer evaluated for possible esophagectomy at our unit was analyzed. Fitness for surgery and postoperative morbidity were used as measures of outcome. The performances of the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) score, the Charlson Comorbidity Index, the age-related Charlson Comorbidity Index (ACCI), the American Society of Anesthesiologists scale and the prognostic nutritional index (PNI) were evaluated in elderly patients. Discrimination was measured with receiver operating characteristics curve analysis; calibration was assessed by the Hosmer-Lemeshow goodness-of-fit test. Age did not result a significant predictor for postoperative complications. In elderly patients, ACCI predicted the judgment of the multidisciplinary team about fitness for surgery with the best discrimination (C-index = 0.94). PNI had the best discrimination for postoperative complications (C-index = 0.71) in the elderly group. ACCI best predicted the fitness for surgery in elderly patients. In elderly patients, the most discriminative prognostic score for postoperative complication was PNI, which could be used at admission for surgery to correctly inform patients about their risk and, possibly, to take extra precaution in case of high risk.

The Italian INFN-Grid Project is committed to set-up, run and manage an unprecedented nation-wide Grid infrastructure. The implementation and use of this INFN-Grid Testbed is presented and discussed. Particular care and attention are devoted to those activities, relevant for the management of the Testbed, carried out by the INFN within international Grid Projects.

The IL-1 family encompasses eleven ligands and ten receptors, which have a key role in different phases of the acute resolving inflammatory defence responses, as well as in the persistent inflammation characteristic of chronic inflammatory diseases. Both inflammatory and anti-inflammatory cytokines are present among the ligands of the IL-1 family, including natural inhibitors/antagonists. IL-1 family receptors include ligand-binding activating receptors, non-binding accessory chains, and ligand-binding non-signalling "decoy" receptors, the latter being able to subtract the agonist ligands from interaction with activating receptors. The proper quantitative and temporal modulation of all these molecules underlies the physiological resolving inflammatory defensive responses, while an imbalance may result in the transition to chronic/pathological inflammation. The human innate/inflammatory response in a tissue can be modelled in vitro by culturing human normal monocytes isolated from blood in conditions that resemble the recruitment from blood into the inflamed site, then the encounter with the inflammatory agents and the development of an inflammatory reaction, and eventually the conditions promoting tissue repair and homeostatic regulation upon resolution. In order to simulate this sequence of events, CD14+ monocytes were exposed sequentially in culture to CCL2 (from 0 to 2 h, 37°C, normoxia), LPS-displaying bacterial vesicles (from 2 to 14 h, 39°C, hypoxia), TNF-? (from 3 to 14 h, 39°C, hypoxia), IFN-? (from 7 to 14 h, 39°C, hypoxia), IL-10 (from 14 to 24 h, 37°C, normoxia), and TGF-? (from 24 to 48 h, 37°C, normoxia). Moreover, by changing the culture conditions, we also reproduced the conditions of persistent/chronic inflammation, such as in rheumatoid arthritis, by exposing CD14+ monocytes in culture to CCL2 (from 0 to 2 h, 37°C, normoxia), a cocktail of bacterial and viral stimuli (LPS, PDG, poly:IC, CpG, from 2 to 7 h, 39°C, hypoxia) and IFN-?, ACPA-PA immune complexes, Survivin, M-CSF and GM-CSF (from 7 to 96 h, 39°C, hypoxia). The modulation of the IL-1 family members in monocytes during the different phases of acute and chronic inflammatory reactions was profiled by transcriptome analysis using RNA-Seq. Expression of the genes for six cytokines (IL1B, IL1A, IL1RN, IL18, IL18BP, IL36G) and four receptors (IL1R1, IL1R2, IL1RAP, SIGIRR) are similarly regulated during the early phase of the acute and chronic inflammatory responses, with the peak of expression between 2 and 14 h. The expression of most of these genes returned to the low basal level during the resolution phase in the acute model (except IL18 that was less expressed than in basal conditions), while it was higher than in fresh monocytes in the chronic model from 24 h on. Exceptions are the genes of the two inhibitors IL18BP and SIGIRR. The former significantly increased from 24 to 96 h, while the latter decreased throughout the entire course of the inflammatory response. The GSEA analysis revealed that in both acute and chronic inflammation the expression of all the IL-1 family members is mainly modulated during the first fourteen hours of stimulation, a period in which it is possible to observe the largest variation of expression. Moreover, the analysis of differentially expressed genes between two consecutive time points confirmed that IL-1 family members are modulated during the entire course of the inflammatory reactions, except between 72 and 96 h in the chronic model where they remain practically unchanged. In conclusion, our results confirm the strong involvement of the IL-1 family genes, especially in the early phases of the monocyte inflammatory response, to underline the central role of IL-1 related cytokines and receptors in initiating innate/nflammatory defensive reactions.

The IL-1 family encompasses eleven ligands and ten related receptors, all key players in different phases of acute and chronic innate/inflammatory response, both in the acute resolving inflammatory defence response, and in the persistent inflammation characteristic of chronic inflammatory diseases. Among IL-1 family ligands there are inflammatory and anti-inflammatory cytokines, including natural inhibitors/antagonists. Among IL-1 family receptors there are both activating, accessory and non-signalling "decoy" receptors, the latter being able to subtract the agonist ligands from interaction with activating receptors. The proper quantitative and temporal modulation of all these molecules underlies the physiological, resolving inflammatory defensive response, while an imbalance may result in the transition to chronic/pathological inflammation. The human innate/inflammatory response in a tissue can be modelled in vitro by culturing human normal monocytes isolated from blood in conditions that resemble the recruitment from blood into the inflamed site, then the encounter with the inflammatory agents, and eventually the conditions promoting tissue repair and homeostatic regulation upon resolution. In order to simulate all these events, CD14+ monocytes were exposed sequentially in culture to CCL2 (from 0 to 2 h, 37°C, normoxia), LPS-displaying bacterial vesicles (from 2 to 14 h, 39°C, hypoxia), TNF-? (from 3 to 14 h, 39°C, hypoxia), IFN-? (from 7 to 14 h, 39°C, hypoxia), IL-10 (from 14 to 24 h, 37°C, normoxia), and TGF-? (from 24 to 48 h, 37°C, normoxia). Moreover, by changing the culture conditions, we also reproduced the conditions of persistent/chronic inflammation, such as in rheumatoid arthritis, exposing CD14+ monocytes in culture to CCL2 (from 0 to 2 h, 37°C, normoxia), a cocktail of bacterial and viral stimuli (LPS, PDG, poly:IC, CpG, from 2 to 7 h, 39°C, hypoxia) and IFN-?, ACPA-PA immune complexes, Survivin, M-CSF and GM-CSF (from 7 to 96 h, 39°C, hypoxia). The modulation of the IL-1 family members during the different phases of acute and chronic inflammatory responses of monocytes were profiled by transcriptome analysis using RNA-Seq. Expression of the genes for six cytokines (IL1B, IL1A, IL1RN, IL18, IL18BP, IL36G) and four receptors (IL1R1, IL1R2, IL1RAP, SIGIRR) are similarly regulated during the early phase of the acute and chronic inflammatory responses, with the peak of expression between 2 and 14 h. The expression of most of them returned to the low basal level during the resolution phase in the acute model (except IL18 that was lower than in basal conditions), while it was higher than in fresh monocytes in the chronic model from 24 h on. Exceptions are the genes of the two inhibitors IL18BP and SIGIRR. The former significantly increased from 24 to 96 h, while the latter decreased throughout the entire inflammatory reaction. The GSEA analysis revealed that in both models the expression of all the IL-1 family members is mainly modulated during the first fourteen hours of stimulation, a period in which it is possible to observe the largest variation of expression. Moreover, the analysis of differentially expressed genes between two consecutive time points confirmed that IL-1 family members are modulated during the entire course of the inflammatory reactions, except between 72 and 96 h in the chronic model where they remain practically unchanged. In conclusion, our results confirm the strong involvement of the IL-1 family genes, especially in the early phases of the monocyte inflammatory response.

The human inflammatory response in a tissue has been modelled in vitro by culturing human normal monocytes isolated from blood in conditions that sequentially reproduce the recruitment from blood into the inflamed site, the encounter with the infectious agents, the subsequent development of an inflammatory reaction ending up with the destruction of the triggering agent, and the eventual resolution with tissue repair and re-establishment of homeostasis. By changing the culture conditions, we could also reproduced the conditions of persistent/chronic inflammation typical of a non-resolving disease. The course of inflammation in the two models was profiled by transcriptome analysis using RNA-Seq, taking the IL-1 family genes as reference. Gene expression of six cytokines (IL1B, IL1A, IL1RN, IL18, IL18BP, IL36G) and four receptors (IL1R1, IL1R2, IL1RAP, SIGIRR) is similarly regulated during the early phase of the acute and chronic inflammatory responses. Expression of most of these genes returned to the low basal level during the resolution phase in the acute model, while it was higher than in fresh monocytes in the late phases of the chronic model. Exceptions are the two inhibitor genes IL18BP and SIGIRR. The GSEA analysis revealed that in both acute and chronic inflammation the expression of all the IL-1 family genes is mainly modulated during the first 14 h, whereas they remain practically unchanged between 72 and 96 h in the chronic model. These data suggest that the IL-1 related cytokines and receptors can be useful biomarkers to discriminating between physiological and pre-pathological inflammatory reactions.

Mitral valve repair has been established as providing increased patient longevity, better cardiac function, and less valve-related complications compared with a prosthetic valve replacement. Repair techniques for degenerative mitral valve disease have included replacement of chordae tendineae, leaflet resections, chordal transfers, and various leaflet sliding maneuvers. Herein, we describe a leaflet edge-to-edge repair technique that provides excellent trans-valve flow characteristics and can be applied to a variety of mitral valve pathologies. It can assist surgeons in repairing complex degenerative mitral disease. Moreover, the technique is very applicable to robot-assisted mitral valve repair. Our large series, and those of others, have been proven this technique to be very efficacious.

First evidence of in vitro cytocompatibility of SiC/SiO2 core-shell nanowires is reported. Different internalization mechanisms by adenocarcinomic alveolar basal epithelial cells, monocytic cell line derived from an acute monocytic leukemia, breast cancer cells, and normal human dermal fibroblasts are shown. The internalization occurs mainly for macropinocytosis and sporadically by direct penetration in all cell models considered, whereas it occurred for phagocytosis only in monocytic leukemia cells. The cytocompatibility of the nanowires is proved by the analysis of cell proliferation, cell cycle progression, and oxidative stress on the cells treated with NWs as compared to controls. Reactive oxygen species generation was detected as an early event that then quickly run out with a rapid decrease only in adenocarcinomic alveolar basal epithelial and human dermal fibroblasts cells. In all the cell lines, the intracellular presence of NWs induce the same molecular events but to a different extent: peroxidation of membrane lipids and oxidation of proteins. The NWs do not elicit either midterm (72 h) or long-term (10 days) cytotoxic activity leading to irreversible cellular damages or death. Our results are important in view of a possible use of SiC/SiO2 core-shell structures acting as biomolecule-delivery vectors or intracellular electrodes.

Even though the Italian Grid Infrastructure (IGI) is a general purpose distributed platform, in the past it has been used mainly for serial computations. Parallel applications have been typically executed on supercomputer facilities or, in case of ``not high-end'' HPC applications, on local commodity parallel clusters. Nowadays, with the availability of multiple cores processors, Grid computing is becoming very attractive also for parallel applications but some problems exist in supporting of HPC applications on Grid environment. Here we describe the work made to set up a HPC testbed for ``not high-end'' HPC applications, based on IGI Grid technologies, to find solutions to those problems. Participating sites have been selected among the ones running HPC clusters in Grid environment. Each of them contributed with their specific HPC experience and their available resources to the present test, which encompasses an unprecedented large set of applications from different disciplines in the fields of astronomy, astrophysics, chemistry, climatology, material science and oceanography. In addition to computing resources sharing, the main contribution of each participant was the identification of the real requirements of his application also related to the current middleware limitations and then the realization of a test platform enhanced with additional HPC solutions and configurations developed in a tight collaboration between HPC administrators, users and IGI managers. The main work was on computational resources selection, data management and the definition, the deployment and the documentation of the software execution environment. The outcoming results of the testbed represent the basis of the HPC support in the IGI production infrastructure.

The Grid Virtual Organization (VO) "Theophys", associated to the INFN (Istituto Nazionale di Fisica Nucleare), is a theoretical physics community with various computational demands, spreading from serial, SMP, MPI and hybrid jobs. That has led, in the past 20 years, towards the use of the Grid infrastructure for serial jobs, while the execution of multi-threaded, MPI and hybrid jobs has been performed in several small-medium size clusters installed in different sites, with access through standard local submission methods. This work analyzes the support for parallel jobs in the scientific Grid middlewares, then describes how the community unified the management of most of its computational need (serial and parallel ones) using the Grid through the development of a specific project which integrates serial e parallel resources in a common Grid based framework. A centralized national cluster is deployed inside this framework, providing "Wholenodes" reservations, CPU affinity, and other new features supporting our High Performance Computing (HPC) applications in the Grid environment. Examples of the cluster performance for relevant parallel applications in theoretical physics are reported, focusing on the different kinds of parallel jobs that can be served by the new features introduced in the Grid.

Responses both to hyperosmotic stress and to heat shock were compared in 3T3 cells, spontaneously transformed cells (ST3T3) and simian virus 40-transformed cells (SV3T3). Cell adaptation to these stresses was measured in terms of surviving cell viability and plating efficiency, while their induced synthesis of stress proteins was monitored in terms of the presence of mRNA for HSP70, the pattern of polypeptides synthesised and the accumulation of HSP70 detectable by monoclonal antibodies. All three types of cells responded similarly to heat shock in their expression of HSP70 and showed no clear differences in ability to recover. In contrast, both ST3T3 and SV3T3 cells adapted more poorly and much more slowly to hyperosmotic stress (0.5 osM incubation) than did normal 3T3 cells. This different pattern of adaptation to hyperosmotic stress was parallelled by the cells' different expression of a stress protein that could not be distinguished from the heat-induced HSP70 by any of the methods listed above. In view of these findings it seems possible that hyperosmotic treatment might be useful in selectively affecting the survival of tumour cells. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6

Ten patients with chronic renal failure (GFR 29–97 ml/min), on free diets providing 1 g/kg B.W. of proteins, ingested an oral protein load (meat meal, 2 g/kg B.W.). GFR and RPF increased significantly over baseline with no change in filtration fraction. Within 30 min of the meal and for the next 3 h a statistically significant increase was observed in the plasma concentrations of the following amino acid groups: essential, nonessential, total, branched-chain, ketogenic, glycogenic, glycogenic and ketogenic, basic, acid, polar and non-polar. At 30 min the smallest increase was seen in acid and polar amino acids (6.7% and 7.6%, respectively). At 180 min the largest increase (78.8%) was seen for glycogenic and ketogenic amino acids and total plasma amino acids were 1.58 times baseline. After the meat meal plasma glucagon and insulin rose significantly, while growth hormone, plasma renin activity and aldosterone did not vary.

S S9 one case from breast cancer. In all three cases HIPEC was performed using Doxorubicin (15 mg/ m) and Cisplatin (25 mg/l/m) for 60 minutes of perfusion. Average follow up time was 6 months. Average age was 56.3 years old. Average operation time was 120 minutes. Main results: In all the patients the treatment lead to a complete resolution of the malignant ascites. Paracentis was no longer necessary after surgery. One patient died after 1 year due to cardiac issues not related to the primary disease. The other two patients are alive and are undergoing systemic chemotherapy treatment. Average survival was 6.3 months. We had no post surgical complications Conclusion: Short operative times, short hospital stays, low complication rates and, ultimately, symptomatic relief are the advantages of laparoscopically administering heated intraperitoneal chemotherapy, making it not only a valuable treatment modality but also the most successful treatment modality for achieving palliative cure of malignant ascites. Further investigations into surveying quality of life remain to be formally studied establishing the real benefit of each newer treatment. http://dx.doi.org/10.1016/j.ejso.2014.10.024 Laparoscopic esophagectomy for cancer: Impact on postoperative inflammatory and nutritional status L. Saadeh*, M. Scarpa, E. Pinto, M. Cagol, R. Alfieri, F. Cavallin, E. Pizzolato, G. Noaro, A. Da Roit, C. Castoro 1 Istituto Oncologico Veneto, Padova, Italy 2 Chirurgia Generale, Azienda Ospedaliera di Padova, Padova, Italy 3 Clinica Chirurgica I, Universit a di Padova, Padova, Italy * Corresponding author: Luca Saadeh, Istituto Oncologico Veneto, Padova, Italy. E-mail address: luca.saadeh@gmail.com (L. Saadeh) Study objective: The purpose of this case-control study was to evaluate the impact of laparoscopic gastric tubulization during esophagectomy for cancer on postoperative inflammatory and nutritional status. Material and methods: We retrospectively evaluated all consecutive patients undergoing laparoscopic gastric tubulization (LGT) during esophagectomy for cancer referred to our surgical unit between 2008 and 2013. A group of patients undergoing esophagectomy with open gastric tubulization (OGT) e matched for neoadjuvant therapy, pathological stage, gender and age e were enrolled as controls. Demographic data, tumor features and post-operative course were compared. In particular, systemic inflammatory and nutritional status was monitored during the postoperative hospital stay. Quality of life was evaluated at one month after surgery using EORTC QLQ-C30 functional scales, EORTC OES-18 Eating scale and EORTC BR23 Body Image scale. Main results: We enrolled 34 patients per group, with similar demographic and tumor characteristics and ASA score. Patients in LGT group had longer procedure (p 1⁄4 0.04). Postoperative course was similar in terms of complication rate and severity and of functional result. ICU length of stay was shorter in patients in the LGT group (p 1⁄4 0.002). In the first postop day LGT patients had lower C-reactive protein (CRP) levels (p 1⁄4 0.001) and white cell blood count (p 1⁄4 0.05), and higher albumin serum level (p 1⁄4 0.001). In this group, albumin remained higher also at third (p 1⁄4 0.06) and seventh (p 1⁄4 0.008) postop day, and CRP resulted lower at third post day (p 1⁄4 0.04). No difference was observed in term of quality of life. Conclusion: LGT during esophagectomy for cancer significantly improved the systemic inflammatory and catabolic response to surgical trauma, contributing to a shorter ICU length of stay. Quality of life and esophageal function were comparable between LGT and OGT patients. http://dx.doi.org/10.1016/j.ejso.2014.10.025 Innate and adaptive immunity activation in neoplastic mucosa in esophageal cancer M. Scarpa*, M. Scarpa, M. Kotsafti, M. Cagol, R. Alfieri, T. Morbin, S. Realdon, G. Battaglia, I. Castagliuolo, C. Castoro 1 Istituto Oncologico Veneto, Padova, Italy 2 Clinica Chirurgica III, Universit a di Padova, Padova, Italy Dipartimento di Medicina Molecolare, Universit a di Padova, Padova, Italy * Corresponding author: Melania Scarpa, Istituto Oncologico Veneto, Padova, Italy. E-mail address: melania.scarpa@inwind.it (M. Scarpa) Study objectives: The expression of costimulatory molecules CD80 and CD86 in the esophageal cancer tissue is significantly lower than in the mucosa of healthy patients and it is inversely correlated to the expression of TGF-beta1 and IL-10. This may be one of the mechanisms of impaired function of dendritic cells and immune escape of cancer cells in the esophageal cancer. The aim of the study is to investigate the interplay between epithelium and CD8 T cells that characterizes the immune environment of EAC. Material and methods: Fresh biopsies (n 1⁄4 32) obtained from healthy esophagus, Barrett’s esophagus, esophageal dysplasia and adenocarcinoma were analysed by flow cytometry to quantify the expression of CD80 on esophageal epithelial cells and, its receptor CD28 and the lymphocytes activation marker CD38 on CD8 infiltrating lymphocytes. Mucosa samples from cancer and from healthy esophagus were obtained during esophagectomy from 58 patients affected by EAC and 12 patients affected by squamous cell cancer (SCC). Frozen samples were analysed with Real Time qPCR for innate immunity (Tlr4, Myd88), costimulatory molecules (Cd80, Cd86), and lymphocytes activation (Cd38, Cd69) genes expression. Immunohistochemistry for CD8 and NK cells cytolytic activity (CD107a) of tumor infiltrating lymphocytes and for CD80 was performed. Non parametrical statistics were used. Main results: Flow cytometric analysis revealed a significant increase of CD80+ esophageal epithelial cells in metaplasia during inflammatory esophageal carcinogenesis. Moreover, Real Time qPCR showed a significant upregulation of Tlr4, MyD88, Cd80, Cd86, Cd38 and Cd69 gene expression in EAC tissues compared to their matched normal tissues. CD80, CD8 and CD107a protein expression was higher in the cancer tissue of patients who underwent neoadjuvant therapy. Finally, the number of intraepithelial CD107a+ cells resulted inversely correlated with tumor differentiation and Mandard tumor regression grade. Conclusion: In inflammation-driven esophageal carcinogenesis there is evidence of an early active immune surveillance process mediated by CD80 overexpression on metaplastic esophageal epithelial cells. Overall, EAC microenvironment shows an inflamed phenotype characterized by the presence of functionally inhibited CD8+ T-cells. Notably, patients who underwent neoadjuvant CT-RT show an increased tumor infiltration of degranulating (CD107+) CD8+ and NK cells. http://dx.doi.org/10.1016/j.ejso.2014.10.026 Preoperative 18-FDG PET predicts survival in resectable pancreatic cancer V. Beltrame*, M. Gruppo, S. Merigliano, S. Bissoli, C. Pasquali, C. Sperti 1 Clinica Chirurgica 3, Padova, Italy Medicina Nucleare, Castelfranco Veneto, Italy * Corresponding author: Valentina Beltrame, Clinica Chirurgica 3, Padova, Italy. E-mail address: valebeltrame@libero.it (V. Beltrame) Study objective: The identification of prognostic factors useful in selecting patients with pancreatic cancer who will benefit from surgery or

The wave areas of visual evoked response (VERI are d imensionally homogenous with electric charges (with an added multiplicative resistive c oefficient) : they translate therefore the ionic transmembrane transports which are concomitant to cortical e xcitation following upon visual s timulation. The postulate of the preservation of charges throughout VER enables the determination of the "aggregate resting potential" of the electrogenerator c erebral cells : it is the temporal axis which would bring about the cancellation of the algebraic sum of all the wave areas (the isoelectric line).

Studies of the responses of porcine pulmonary endothelial cells to acute hypertonic stress have been extended by examining the induction and underlying mechanisms of cell tolerance to both osmotic and heat stresses. Preliminary adaptation of these cells to 0.4osmol (kg H(2)O)(-1) rendered them tolerant either to subsequent severe osmotic stress (0.7osmol (kg H(2)O)(-1)) or to subsequent severe heat shock (50 min at 49 degrees C). In contrast, preliminary exposure of the cells to mild heat shock (44 degrees C for 30 min) induced tolerance only to severe heat shock, not to hyperosmotic stress. Induction of tolerance to heat shock by either procedure correlated with the induced expression of heat shock protein 70 (HSP70). Induction of tolerance to hyperosmotic stress, on the other hand, was associated with the cellular accumulation of osmolytes, such as amino acids, betaine and myo-inositol, and did not correlate with the induced expression of HSP70. It also required a reduction in the final change of osmotic pressure applied to the cells, such that maximum cell shrinkage would not be much more than 40%. In general, therefore, HSP70 and compatible osmolytes have distinct roles in cellular adaptation to these stresses.