MiR-21 up-regulation in ampullary adenocarcinoma and its pre-invasive lesions

Poor information is available on the molecular landscape characterizing the carcinogenetic process leading to ampullary carcinoma. MiR-21 is one of the most frequently up-regulated miRNAs in pancreatic adenocarcinoma, a tumor sharing similar molecular features with ampullary adenocarcinomas (AVCs), above all with the pancreatic-biliary type. We profiled, by in situ hybridization (ISH), miR-21 expression in a series of 26 AVCs, 50 ampullary dysplastic lesions (35 low-grade [LG-IEN] and 15 high-grade [HG-IEN]) and 10 normal duodenal mucosa samples. The same series was investigated by immunohistochemistry for β-catenin, p53 and HER2 expression. HER2 gene amplification was evaluated by chromogenic in situ hybridization. To validate miR-21 ISH results we performed miR-21 qRT-PCR analysis in a series of 10 AVCs and their matched normal samples. All the normal control samples showed a negative or faint miR-21 expression, whereas a significant miR-21 up-regulation was observed during the carcinogenetic cascade (p < 0.001), with 21/26 (80.8%) of cancer samples showing a miR-21 overexpression. In comparison to control samples, a significant overexpression was found in samples of LG-IEN (p = .0003), HG-IEN (p = .0001), and AVCs (p < 0.0001). No significant difference in miR-21 overexpression was observed between LG-IEN, HG-IEN and AVCs. By qRT-PCR analysis, AVCs showed a 1.7-fold increase over the controls (p = .003). P53 was frequently dysregulated in both dysplastic and carcinoma samples (44 out of 76; 57.9%). A 20% (10/50) of dysplastic lesions and 11% (3/26) of carcinomas were characterized by a nuclear localization of β-catenin. Only 2 AVCs (7.7%; both intestinal-type) showed a HER2 overexpression (both 2+), which corresponded to a HER2 gene amplification at CISH analysis. This is the first study demonstrating a miRNA dysregulation in the whole spectrum of ampullary carcinogenesis. MiR-21 overexpression is an early molecular event during ampullary carcinogenesis and its levels increase with the neoplastic progression

DNA methylation patterns identify subgroups of pancreatic neuroendocrine tumors with clinical association

Here we report the DNA methylation profile of 84 sporadic pancreatic neuroendocrine tumors (PanNETs) with associated clinical and genomic information. We identified three subgroups of PanNETs, termed T1, T2 and T3, with distinct patterns of methylation. The T1 subgroup was enriched for functional tumors and ATRX, DAXX and MEN1 wild-type genotypes. The T2 subgroup contained tumors with mutations in ATRX, DAXX and MEN1 and recurrent patterns of chromosomal losses in half of the genome with no association between regions with recurrent loss and methylation levels. T2 tumors were larger and had lower methylation in the MGMT gene body, which showed positive correlation with gene expression. The T3 subgroup harboured mutations in MEN1 with recurrent loss of chromosome 11, was enriched for grade G1 tumors and showed histological parameters associated with better prognosis. Our results suggest a role for methylation in both driving tumorigenesis and potentially stratifying prognosis in PanNETs

DNA methylation patterns identify subgroups of pancreatic neuroendocrine tumors with clinical association

Here we report the DNA methylation profile of 84 sporadic pancreatic neuroendocrine tumors (PanNETs) with associated clinical and genomic information. We identified three subgroups of PanNETs, termed T1, T2 and T3, with distinct patterns of methylation. The T1 subgroup was enriched for functional tumors and ATRX, DAXX and MEN1 wild-type genotypes. The T2 subgroup contained tumors with mutations in ATRX, DAXX and MEN1 and recurrent patterns of chromosomal losses in half of the genome with no association between regions with recurrent loss and methylation levels. T2 tumors were larger and had lower methylation in the MGMT gene body, which showed positive correlation with gene expression. The T3 subgroup harboured mutations in MEN1 with recurrent loss of chromosome 11, was enriched for grade G1 tumors and showed histological parameters associated with better prognosis. Our results suggest a role for methylation in both driving tumorigenesis and potentially stratifying prognosis in PanNETs

Durability-Based Design of Structures Made with Ultra-High-Performance/Ultra-High-Durability Concrete in Extremely Aggressive Scenarios: Application to a Geothermal Water Basin Case Study

This paper provides the formulation and description of the framework and methodology for a Durability Assessment-based Design approach for structures made of the Ultra-High-Durability Concrete materials conceived, produced and investigated in the project ReSHEALience (Rethinking coastal defence and Green-energy Service infrastructures through enHancEd-durAbiLity high-performance cement-based materials) funded by the European Commission within the Horizon 2020 Research and Innovation programme (Call NMBP 2016–2017 topic 06-2017 GA 780624). The project consortium, coordinated by Politecnico di Milano, gathers 13 partners from 7 countries, including 6 academic institutions and 7 industrial partners, covering the whole value chain of the concrete construction industry. The innovative design concept informing the whole approach herein presented has been formulated shifting from a set of prescriptions, mainly referring to material composition and also including, in case, an allowable level of damage defined and quantified in order not to compromise the intended level of “passive” protection of sensitive material and structural parts (deemed-to-satisfy approach; avoidance-of-deterioration approach), to the prediction of the evolution of the serviceability and ultimate limit state performance indicators, as relevant to the application, as a function of scenario-based aging and degradation mechanisms. The new material and design concepts developed in the project are being validated through design, construction and long-term monitoring in six full-scale proofs-of concept, selected as representative of cutting edge economy sectors, such as green energy, Blue Growth and conservation of R/C heritage. As a case study example, in this paper, the approach is applied to a basin for collecting water from a geothermal power plant which has been built using tailored Ultra-High-Durability Concrete (UHDC) mixtures and implementing an innovative precast slab-and-buttress structural concept in order to significantly reduce the thickness of the basin walls. The geothermal water contains a high amount of sulphates and chlorides, hence acting both as static load and chemical aggressive. The main focus of the analysis, and the main novelty of the proposed approach is the prediction of the long-term performance of UHDC structures, combining classical structural design methodologies, including, e.g., cross-section and yield line design approaches, with material degradation laws calibrated through tailored tests. This will allow us to anticipate the evolution of the structural performance, as a function of exposure time to the aggressive environment, which will be validated against continuous monitoring, and pave the way towards a holistic design approach. This moves from the material to the structural durability level, anticipating the evolution of the structural performance and quantifying the remarkable resulting increase in the service life of structures made of UHDC, as compared to companion analogous ones made with ordinary reinforced concrete solutions

Structural validation of geothermal water basins constructed with durability enhanced ultra high performance fiber reinforced concrete (Ultra High Durability Concrete)

Ultra-High Performance Concrete (UHPC) proved to be very durable in harsh environments, primarily because of the extremely low porosity of the matrix (uncracked). However, the limited availability of design standards is still a barrier to widespread applications of UHPC, together with still limited knowledge of its durability in the real (cracked) service conditions. In this paper, the use of tailored UHPC is introduced, whose composition has been specifically designed to achieve enhanced durability in the cracked state combined with extremely aggressive environments. Validation of the material and structural design concept on a full scale structure is presented, with reference to a tank intended to contain geothermal water from the cooling tower at a geothermal power plant. This pilot structure was designed and constructed using both ordinary reinforced concrete and durability enhanced UHPC, which is called hereafter Ultra High Durability Concrete (UHDC), for comparative assessment purposes. Upon the completion of the pilot construction and entering its service life, periodic assessment and validation tests have been carried out to validate the structural design assumptions and to check the serviceability requirements. Results of these tests, performed over the span of two years are reported in detail in this paper to validate the material and structural concepts. The study highlights the most important parameters that could affect the performance of UHPC structures during casting and service life. The overall project framework presented in this paper has to be intended as a pioneer study in moving towards a performance based durability-design approach for UHPC structures

Innovative Design Concept of Cooling Water Tanks/Basins in Geothermal Power Plants Using Ultra-High-Performance Fiber-Reinforced Concrete with Enhanced Durability

The structure presented in this paper is intended to be used as a prototype reservoir for collecting water coming from the cooling tower of a geothermal plant, and is primarily designed to compare the performance of different materials (traditional reinforced concrete and Ultra-High-Performance Fiber-Reinforced Concrete (UHPFRC)) as well to assess the performance of different structural solutions (wall with constant thickness versus wall provided with stiffening buttresses). In the absence of specific code provisions, given the novelty of the UHPFRC used, the main properties used for the design were determined through a dedicated experimental campaign (tensile/flexural properties and shrinkage). The main focus of the design was on the Serviceability Limit States, more specifically the requirements regarding water tightness. Given the rather simple structural layout, especially in the compartments where no stiffening buttresses are present, linear elastic analysis was used to determine the internal actions. The nonlinear behavior ensuing from the peculiar tensile constitutive response of the material was taken into account locally, in order to determine the stress level, the depth of the compression zone and the crack width. The performance was finally compared with the reference compartment (made with ordinary reinforced concrete), through on-site observations and measurements

Impact of extra-ampullary duodenal adenocarcinoma subtypes on surgical and oncological outcomes following pancreaticoduodenectomy

Background: There is little information about the relevance of extra-ampullary duodenal adenocarcinoma (EDA) subtypes. The aim of this study was to evaluate the impact of EDA subtypes on surgical and oncological outcomes following pancreatoduodenectomy (PD). Methods: Consecutive patients undergoing PD for EDA from 2000 to 2019 were analyzed. Results were stratified by pathologic subtype (intestinal versus non-intestinal). Uni-and multivariable analyses were performed using standard statistical methods. Results: The study population consisted of 70 patients, of whom 49 (70%) had an intestinal phenotype. EDA with intestinal phenotype was more frequently proximal to the Ampulla of Vater, while non-intestinal EDA was more frequently found distally (76% vs. 33%, p = 0.002). Patients with intestinal EDA were less likely to experience severe morbidity, with decreased reoperation and unplanned Intensive Care Unit admission rates relative to non-intestinal subtypes (2% vs. 29% p = 0.002, and 2% vs. 19%, p = 0.007, respectively). The median follow-up post-pancreatectomy was 73 months. Intestinal EDA was associated with improved overall and disease-free survival, with 3-year and 5-year survival rates of 71% vs. 29% and 53% vs. 24%, respectively. (p = 0.019 and p = 0.025). Conclusion: Intestinal-type EDA, which more often arises from supra-ampullary duodenum, was associated with better postoperative outcomes and improved survival

Il teatro gay in Italia

La messa in scena della Traviata Norma a Milano nel 1976 apre la breve stagione del “teatro gay” in Italia. Dieci anni dopo, con Fascistissima del KGB&B al Cassero di Bologna, si chiude il periodo del teatro omosessuale militante: le tematiche elaborate in quegli anni, così come gli stili e i codici scenici consolidati nell’ambito culturale LGBT, continueranno a esercitare la loro influenza negli anni a venire, non solo a teatro ma anche nel cinema e nei media. Questo volume raccoglie otto testi che formano una sorta di “canone” del teatro omosessuale in Italia e aggiunge due importanti testimonianze coeve, apparse sulla rivista «Scena», che restituiscono il clima culturale nel quale nacquero quelle opere. L’inquadramento storico è agevolato da brevi schede che precedono ogni testo e da una larga introduzione che descrive lo sviluppo della tematica omosessuale negli anni precedenti, focalizzando l’attenzione su quattro importanti lavori: La governante, Anima Nera, L’Arialda, Persone naturali e strafottenti