Influence of Myocardial Fibrosis on Left Ventricular Hypertrophy in Patients with Symptomatic Severe Aortic Stenosis.

Aim: It was the aim of our study to determine whether myocardial fibrosis influences physiologic or non-physiologic left ventricular (LV) hypertrophy in severe aortic stenosis. Methods: Myocardial fibrosis was evaluated using specimens taken from the ventricular septum in 79 patients submitted to aortic valve replacement because of symptomatic aortic stenosis. Patients were considered to have physiologic LV hypertrophy if end-systolic wall stress, evaluated by echocardiography, was 90 kdyn/cm(2) were considered to have non-physiologic hypertrophy. Results: Fibrosis tissue mass index was significantly inversely related with LV fractional shortening and directly related with LV diastolic and systolic diameter and LV mass index (LVMI). Patients with non-physiologic hypertrophy (n = 24) had a higher LVMI due to larger LV diastolic and systolic diameters with thinner wall, resulting in lower relative wall thickness. These patients had a higher fibrosis tissue mass index and impaired LV systolic and diastolic functions, as suggested by lower LV fractional shortening and higher mean wedge pressure. At follow-up of 7.4 \ub1 2.1 months, the LVMI and New York Heart Association class remained higher in patients with non-physiologic hypertrophy. Conclusions: Our study suggests a different quality of hypertrophies in patients with aortic stenosis, where myocardial fibrosis seems to be the critical abnormality that differentiates adaptive from maladaptive response to increased afterload

hERG1 Potassium Channel Expression in Colorectal Adenomas: Comparison with Other Preneoplastic Lesions of the Gastrointestinal Tract

Preneoplastic lesions represent a useful target for early diagnosis and follow-up of gastrointestinal malignancies. hERG1 channel expression was tested by immunohistochemistry (IHC) in a cohort of colorectal adenoma samples belonging to Italian subjects. Overall, hERG1 was expressed in 56.5% of cases with both high staining intensity and a high percentage of positive cells. Moreover, hERG1 was expressed in a higher percentage of dysplastic adenomas with respect to hyperplastic lesions, and the proportion of positive samples further increased in patients with high-grade dysplasia. Comparing hERG1 expression in other preneoplastic lesions of the GI tract (gastric dysplasia and Barrett’s esophagus), it emerged that in all the conditions, hERG1 was expressed with a diffused pattern, throughout the cell, with variable staining intensity within the samples. The highest expression was detected in gastric dysplasia samples and the lowest in Barrett’s esophagus at similar levels observed in colorectal adenomas. Our results show that hERG1 is aberrantly expressed in human preneoplastic lesions of the gastrointestinal tract and has a different pattern of expression and role in the different sites. Overall, the detection of hERG1 expression in preneoplastic lesions could represent a novel diagnostic or prognostic marker of progression in the gastrointestinal tract

The hERG1 potassium channel behaves as prognostic factor in gastric dysplasia endoscopic samples

Purpose: Gastric cancer (GC) is still a relevant health issue worldwide. The identification of prognostic factors for progression of gastric dysplasia (GD), the main pre-cancerous lesion of the intestinal-type GC, is hence mandatory.Patients and methods: A cohort of 83 GD endoscopic samples belonging to Italian subjects was collected. hERG1 expression was evaluated by immunohistochemistry and scored 0-3, depending on the percentage of stained cells. Expression data were analysed in conjunction with clinico-pathological and survival data.Results: hERG1 turned out to be expressed in 67.47% (56 out of 83) of the GD samples. hERG1 expression was higher in high-grade GD compared to low-grade GD (29 out of 39, 74.36% vs 27 out of 44, 61.36%), although the statistical significance was not reached (P=0.246). No association emerged between hERG1 expression and clinical features of the patients (age, gender, localization, H. pylori infection, gastritis and intestinal metaplasia). In a subset of cases for which sequential samples of gastric lesions (from GD to Early Gastric Cancer and Advanced Gastric Cancer) were available, hERG1 expression was maintained in all the steps of gastric carcinogenesis from GD onwards. A general trend to increased expression in advanced lesions was observed. hERG1 score had a statistically significant impact on both Progression-Free Survival (P=0.018) and Overall Survival (P=0.031). In particular, patients displaying a high hERG1 score have a shorter survival.Conclusion: hERG1 is aberrantly expressed in human GD samples and has an impact on both PFS and OS, hence representing a novel prognostic marker for progression of GD towards GC of the intestinal histotype. Once properly validated, hERG1 detection could be included in the clinical practice, during endoscopic surveillance protocols, for the management of GD at higher risk of progression, as already proposed for Barrett's oesophagus

Comprehensive molecular portrait using next generation sequencing of resected intestinal-type gastric cancer patients dichotomized according to prognosis

In this study, we evaluated whether the presence of genetic alterations detected by next generation sequencing may define outcome in a prognostically-selected and histology-restricted population of resected gastric cancer (RGC). Intestinal type RGC samples from 34 patients, including 21 best and 13 worst prognostic performers, were studied. Mutations in 50 cancer-associated genes were evaluated. A significant difference between good and poor prognosis was found according to clinico-pathologic factors. The most commonly mutated genes in the whole population were PIK3CA (29.4%), KRAS (26.5%), TP53 (26.5%) MET (8.8%), SMAD4 (8.8%) and STK11 (8.8%). Multiple gene mutations were found in 14/21 (67%) patients with good prognosis, and 3/13 (23%) in the poor prognosis group. A single gene alteration was found in 5/21 (24%) good and 6/13 (46%) poor prognosis patients. No mutation was found in 2/21 (9.5%) and 4/13 (31%) of these groups, respectively. In the overall series, ß-catenin expression was the highest (82.4%), followed by E-Cadherin (76.5%) and FHIT (52.9%). The good prognosis group was characterized by a high mutation rate and microsatellite instability. Our proof-of-principle study demonstrates the feasibility of a molecular profiling approach with the aim to identify potentially druggable pathways and drive the development of customized therapies for RGC

Multiple thermochronometers applied to the quantitative analysis of compressive systems: The southern sub-Andean fold and thrust belt of Bolivia: From source rock to trap

The evolution of fold and thrust belts requires time data restrictions to determine the rates related to the interaction of surface and subsurface processes and to quantify the time relationship between the components of the petroleum system: reservoir, seal, source rock and trap. The sub-Andean fold-and-thrust belt in the Bolivian territory in general, and the regional transect that links the structures of Curuyuqui-Carohuaicho-Tatarenda-Borebigua-Charagua and Mandeyapecua in particular, constitutes a complex multi-variable system in which the definition of time-Temperature (t-T) trajectories has led to new suitable structural and stratigraphic conclusions. The integration of multiple thermochronological-geochronological systems (Apatite Fission Track, Apatite (U-Th-Sm)/He and UPb SHRIMP on zircon) and the existing surface and subsurface geological constraints made it possible to develop a chrono-kinematic characterization of fault-related anticlines, defining their formation chronology, structural growth rate and link between them in the study area. Furthermore, it was also possible to perform a quantitative analysis of the subsidence-burial and exhumation-erosion phenomena that occurred from the deposition of Silurian-Devonian source rocks to the present time, providing relevant determinations to the modeling of the Oil & Gas system.Fil: Hernandez, Juan I.. Geomap S.a.; ArgentinaFil: Hernández, Roberto M.. Geomap S.a.; ArgentinaFil: Dalenz Farjat, Alejandra. Geomap S.a.; ArgentinaFil: Cristallini, Ernesto Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Geología. Laboratorio de Modelado Geológico; ArgentinaFil: Alvarez, Luis A.. Geomap S.a.; ArgentinaFil: Dellmans, Luis M.. Geomap S.a.; ArgentinaFil: Costilla, Marcos Roberto. Geomap S.a.; ArgentinaFil: Alvarez, Andres F.. Geomap S.a.; ArgentinaFil: Becchio, Raul Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Bio y Geociencias del NOA. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Museo de Ciencias Naturales. Instituto de Bio y Geociencias del NOA; ArgentinaFil: Bordese, Sofia. lA - Te Andes S.A. Laboratorio de Termocronología de Los Andes; ArgentinaFil: Arzadún, Guadalupe. lA - Te Andes S.A. Laboratorio de Termocronología de Los Andes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Guibaldo, Cristina. lA - Te Andes S.A. Laboratorio de Termocronología de Los Andes; ArgentinaFil: Glasmacher, Ulrich A.. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Tomezzoli, Renata Nela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Stockli, Daniel F.. University of Texas; Estados UnidosFil: Fuentes, Facundo. YPF - Tecnología; ArgentinaFil: Soria Galvarro, Jaime. YPF - Tecnología; ArgentinaFil: Rosales, Adolfo. YPF - Tecnología; ArgentinaFil: Dzelalija, Francisco. YPF - Tecnología; ArgentinaFil: Haring, Claudio. YPF - Tecnología; Argentin

hERG1 Channels Regulate VEGF-A Secretion in Human Gastric Cancer: Clinicopathological Correlations and Therapeutical Implications

Purpose: hERG1 channels are aberrantly expressed in several types of human cancers, where they affect different aspects of cancer cell behavior. A thorough analysis of the functional role and clinical significance of hERG1 channels in gastric cancer is still lacking. Experimental Design: hERG1 expression was tested in a wide (508 samples) Italian cohort of surgically resected patients with gastric cancer, by immunohistochemistry and real-time quantitative PCR. The functional link between hERG1 and the VEGF-A was studied in different gastric cancer cell lines. The effects of hERG1 and VEGF-A inhibition were evaluated in vivo in xenograft mouse models. Results: hERG1 was positive in69% of the patients and positivity correlated with Lauren's intestinal type, fundus localization of the tumor, G1-G2 grading, I and II tumor-node-metastasis stage, and VEGF-A expression. hERG1 activity modulated VEGF-A secretion, through an AKT-dependent regulation of the transcriptional activity of the hypoxia inducible factor. Treatment of immunodeficient mice xenografted with human gastric cancer cells, with a combination of hERG1 blockers and anti-VEGF-A antibodies, impaired tumor growth more than single-drug treatments. Conclusion: Our results show that hERG1 (i) is aberrantly expressed in human gastric cancer since its early stages; (ii) drives an intracellular pathway leading to VEGF-A secretion; (iii) can be exploited to identify a gastric cancer patients' group where a combined treatment with antiangiogenic drugs and noncardiotoxic hERG1 inhibitors could be proposed. © 2014 American Association for Cancer Research

Palazzo Trento, Papafava

Il contributo prende in esame la decorazione ad affresco di uno dei palazzi pi\uf9 magniloquenti di Padova, edificato dall'architetto Giambattista Novello su incarico del conte Giambattista Trento. Nel 1764 Francesco Zugno firma e data il grandioso affresco del salone, fulcro del ciclo che interessa anche lo scalone e l'atrio. Le apparizioni del carro del Sole con Zefiro e Flora, delle Stagioni con il Solstizio d'Estate e il Solstizio d'inverno trovano posto nei cieli illusionisticamente aperti sui soffitti dello scalone e del salone, mentre le coppie olimpiche di Mercurio-Minerva e Apollo-Diana sono immaginati come bassorilievi nei due ambienti che affiancano il vano principale. Secondo una tipologia riscontrabile anche altre residenze padovane di questi stessi decenni - palazzo Maldura e palazzo Emo Capodilista, per non citare esempi veneziani - ai personaggi della mitologia vengono affiancati brani di vita contemporanea nelle figure affacciate ai finti balconcini delle pareti, in bilico tra finzione pittorica e verosimiglianza. Nel 1806 Alessandro Papafava acquisir\ue0 lo stabile, dando l'avvio alla seconda, importantissima fase decorativa del palazzo, non presa in esame in questa sede. Quello su palazzo Trento Papafava, infatti, \ue8 un capitolo di un volume - di cui l'autore \ue8 anche co-curatore - che raccoglie per la prima volta i risultati di una ricerca sistematica sugli affreschi del Sei e Settecento nei palazzi di Padova. Nel complesso sono stati analizzati 31 cicli pittorici ad affresco che coprono il periodo dal Barocco al Neoclassicismo. I testi monografici dedicati ai singoli edifici sono preceduti da tre saggi trasversali che inquadrano gli episodi in un orizzonte pi\uf9 ampio di riferimento (committenza, questioni di gusto, tipologie decorative....). Parte integrante \ue8 costituita dall'importante corredo iconografico di oltre 470 immagini. Il libro \ue8 stato promosso dalla Associazione "La Torlonga onlus" nell'ambito del bando \u201cCulturalmente innovare con l\u2019arte e la cultura\u201d 2016 finanziato dalla Fondazione Cassa di Risparmio di Padova e Rovigo e ha visto come attore principale il Dipartimento dei Beni Culturali dell'Universit\ue0 degli Studi di Padova. Quest'ultimo ha messo a disposizione le competenze da lungo tempo affinate in questo specifico ambito di studi e il proprio archivio fotografico, sia quello storico, sia quello derivato da pi\uf9 recenti campagne, finanziate anche da un Progetto di Rilevante Interesse Nazionale, bando 2010-2011