Molecular basis of cardiomiopathy

2016 - 2017The normal heart rhythm is guaranteed by an important intercellular junctions system, named Gap Junction (GJs). Each GJs consists of two units called connexons formed by six specific trans-membrane proteins named connexins (Cx). Recent reports suggest the presence of Cx43 in the inner mitochondrial membrane where it plays an important cardioprotection mechanism. Alterations in Cx43 expression and distribution were observed in several myocardium disease; i.e. in hypertrophic cardiomyopathy, heart failure and ischemia. Thus, in this doctoral study, we investigated the role of Cx43, and in particular of mitochondrial Cx43, in different cardiomyopaties models... [edited by Author]XXX cicl

Role of connexin 43 in cardiovascular diseases

Gap junctions (GJs) channels provide the basis for intercellular communication in the cardiovascular system for maintenance of the normal cardiac rhythm, regulation of vascular tone and endothelial function as well as metabolic interchange between the cells. They allow the transfer of small molecules and may enable slow calcium wave spreading, transfer of "death" or of "survival" signals. In the cardiomyocytes the most abundant isoform is Connexin 43 (Cx43). Alterations in Cx43 expression and distribution were observed in myocardium disease; i.e. in hypertrophic cardiomyopathy, heart failure and ischemia. Recent reports suggest the presence of Cx43 in the mitochondria as well, at least in the inner mitochondrial membrane, where it plays a central role in ischemic preconditioning. In this review, the current knowledge on the relationship between the remodeling of cardiac gap junctions and cardiac diseases are summarized

Doxorubicin-Mediated Cardiotoxicity: Role of Mitochondrial Connexin 43

Doxorubicin is the highly effective anthracycline, but its clinical use is limited by cardiotoxicity and consequent dysfunction. It has been proposed that the etiology of this is related to mitochondrial dysfunction. Connexin 43 (Cx43), the principal protein building block of cardiac gap junctions and hemichannels, plays an important role in cardioprotection. Recent reports confirmed the presence of Cx43 in the mitochondria as well. In this study, the role of mitochondrial Cx43 was evaluated 3 or 6 h after Doxorubicin administration to the rat heart cell line H9c2. Pharmacological inhibition of Hsp90 demonstrated that the mitochondrial Cx43 conferred cardioprotection by reducing cytosolic and mitochondrial reactive oxygen species production, mitochondrial calcium overload and mitochondrial membrane depolarization and cytochrome c release. In conclusion, our study demonstrates that Cx43 plays an important role in the protection of cardiac cells from Doxorubicin-induced toxicity

Speed of updating online evidence based point of care summaries: prospective cohort analysis

Objective To evaluate the ability of international point of care information summaries to update evidence relevant to medical practice

Sodium citrate supplementation: An updated revision and practical recommendations on exercise performance, hydration status, and potential risks

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A peculiar Spanish Timber Floor, the "Revoltón": a Diagnostic Example at the "Palacio del Marqués de Benicarló"

The paper deals with the application of the Italian method for assessing on-site and diagnosing timber elements to a distinctive Spanish type of horizontal structure called "revolton" i.e. jack arch floor. As in Spain does not exist a specific regulation for the on-site diagnosis of timber elements, this analysis was performed according to the Italian standard UNI 11119. Due to the peculiar features of the jack arch floor some modifications were applied to the method. During spring 2012 the authors had the opportunity to carry out a pilot project by making a diagnostic analysis on a whole three stories building. The building, Marquees of Benicarlo's Palace, located in Spain in the town of Benicarlo, between Barcelona and Valencia, was erected during the second half of the XVIII century. It maintains the original internal distribution and structure, and it is characterized by precious ceramic decorations on walls and floors. All the horizontal structures studied inside the palace were jack arch floor except the roof structure that was also made of timber. The results of the project described in the paper clarify the specific problems of the horizontal structures and the roof surveyed during the fieldwork. These results are accompanied by several plans that represent the information recovered on-site and lead to a complete assessment of the structures. The plans include the grading based on wood defects, the local moisture content of wood, the superficial and inner decay due to insects and rot and the deformation of the joists. In this way it was possible to locate the areas of the palace where more problems were concentrated, and better understand the causes and origin of the damages.Diodato, M.; Macchioni, N.; Brunetti, M.; Pizzo, B.; Nocetti, M.; Burato, P.; Sozzi, L.... (2013). A peculiar Spanish Timber Floor, the "Revoltón": a Diagnostic Example at the "Palacio del Marqués de Benicarló". Advanced Materials Research. 778:1064-1071. doi:10.4028/www.scientific.net/AMR.778.1064S10641071778E. Cubero, El lujo señorial de lo sencillo (The noble luxury of simplicity), Revistart: Revista de las artes, 125 (2007) pp.8-10.C. Colón de Carvajal y Fibla, La casa-palacio de los Marqueses de Benicarló (The Marquees of Benicarló's Palace), Numen. Revista de excelencia, (2011) on-line.La casa de los Marqueses de Benicarló nos abre sus puertas (The Marquees of Benicarló's House opens its doors), MasQrural, 21 (2008) pp.85-94.M. Diodato, Variaciones constructivas y formales en forjados y cubiertas (Constructive and formal variations in floors and roofs), in: F. Vegas, C. Mileto, Valencia. Centro histórico. Ocho siglos de arquitectura residencial (Historic centre. Eight Centuries of residential architecture), Generalitat Valenciana, Valencia, (2013).N. Macchioni, Inspection techniques for ancient wooden structures, in: P. Roca, J.L. Gonzalez, E. Onate, P.B. Lourenco (Eds. ), Structural analysis of historical constructions II: possibilities of numerical and experimental techniques, CIMNE, Barcelona, 1998, pp.149-162.N. Macchioni, M. Piazza, Italian standardization activity in the field of diagnosis and restoration of ancient timber structures, in: F.M. Mazzolani (Ed. ), Protection of historical buildings - PROHITECH 09, vol. 1-2, Taylor & Francis Group, London, 2009, pp.349-353.G. Lear, B. Kasal, R. Anthony, Resistance drilling, in: B. Kasal, T. Tannert (Eds. ), In situ assessment of structural timber, State of the art report of the RILEM TC 215-AST, Springer.N. Macchioni, M. Brunetti, B. Pizzo, P. Burato, M. Nocetti, S. Palanti, The timber structures in the Church of the Nativity in Bethlehem: Typologies and diagnosis, Journal of cultural heritage, Vol. 13 Issue 4 Supplement S (2012) pp. E42-E53

Understanding Spanish Timber Jack Arch Floors: Examples of Assessment and Conservation Issues

[EN] Jack arch floors are structures made of timber joists, with round or squared section, and segmental vaults either made of flat tiles or poured plaster conglomerate. They are especially diffused along the Mediterranean coast of Spain and can be considered as a main feature of the historical and vernacular architecture of the area. In order to assess and grade these structures several Spanish standards have been considered; however, even if the information contained is useful the Italian standard for the on-site diagnosis UNI 11119 of 2004 has been preferred. The method described in this standard leads the assessment through the grading of each and every timber element and the assignation of bearing properties that are essential for the consolidation project. This article will expose three examples of jack arch floors of the Valencian Community graded using the Italian standard and the conservation issues that arise from the results.Diodato, M.; Macchioni, N.; Brunetti, M.; Pizzo, B.; Nocetti, M.; Burato, P.; Sozzi, L.... (2015). Understanding Spanish Timber Jack Arch Floors: Examples of Assessment and Conservation Issues. International Journal of Architectural Heritage. 9(6):641-654. https://doi.org/10.1080/15583058.2015.104119364165496Diodato, M., Macchioni, N., Brunetti, M., Pizzo, B., Nocetti, M., Burato, P., … Mileto, C. (2013). A Peculiar Spanish Timber Floor, the «Revoltón»: A Diagnostic Example at the «Palacio del Marqués de Benicarló». Advanced Materials Research, 778, 1064-1071. doi:10.4028/www.scientific.net/amr.778.1064Lear, G., Kasal, B., & Anthony, R. (2010). Resistance Drilling. RILEM State of the Art Reports, 51-57. doi:10.1007/978-94-007-0560-9_5Macchioni, N., Brunetti, M., Pizzo, B., Burato, P., Nocetti, M., & Palanti, S. (2012). The timber structures in the Church of the Nativity in Bethlehem: Typologies and diagnosis. Journal of Cultural Heritage, 13(4), e42-e53. doi:10.1016/j.culher.2012.10.004Riggio, M., Anthony, R. W., Augelli, F., Kasal, B., Lechner, T., Muller, W., & Tannert, T. (2013). In situ assessment of structural timber using non-destructive techniques. Materials and Structures, 47(5), 749-766. doi:10.1617/s11527-013-0093-6Tannert, T., Anthony, R. W., Kasal, B., Kloiber, M., Piazza, M., Riggio, M., … Yamaguchi, N. (2013). In situ assessment of structural timber using semi-destructive techniques. Materials and Structures, 47(5), 767-785. doi:10.1617/s11527-013-0094-5Vegas, F. (2013). Parameterisation of Gypsum Mortar for Alternative Structural Consolidation of Traditional Floors. Advances in Materials, 2(4), 48. doi:10.11648/j.am.20130204.1

Standardization of body composition status in patients with advanced urothelial tumors: the role of a CT-based aI-powered software for the assessment of sarcopenia and patient outcome correlation

Background: Sarcopenia is a well know prognostic factor in oncology, influencing patients' quality of life and survival. We aimed to investigate the role of sarcopenia, assessed by a Computed Tomography (CT)-based artificial intelligence (AI)-powered-software, as a predictor of objective clinical benefit in advanced urothelial tumors and its correlations with oncological outcomes. Methods: We retrospectively searched patients with advanced urothelial tumors, treated with systemic platinum-based chemotherapy and an available total body CT, performed before and after therapy. An AI-powered software was applied to CT to obtain the Skeletal Muscle Index (SMI-L3), derived from the area of the psoas, long spine, and abdominal muscles, at the level of L3 on CT axial images. Logistic and Cox-regression modeling was implemented to explore the association of sarcopenic status and anthropometric features to the clinical benefit rate and survival endpoints. Results: 97 patients were included, 66 with bladder cancer and 31 with upper-tract urothelial carcinoma. Clinical benefit outcomes showed a linear positive association with all the observed body composition variables variations. The chances of not experiencing disease progression were positively associated with ∆_SMI-L3, ∆_psoas, and ∆_long spine muscle when they ranged from ~10-20% up to ~45-55%. Greater survival chances were matched by patients achieving a wider ∆_SMI-L3, ∆_abdominal and ∆_long spine muscle. Conclusions: A CT-based AI-powered software body composition and sarcopenia analysis provide prognostic assessments for objective clinical benefits and oncological outcomes

Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: The Pros-IT CNR study

Background: The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. Methods: One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). Results: At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. Conclusions: Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care