Cell death pathology: Perspective for human diseases

AbstractApoptosis, a genetically regulated form of cell death with distinct biochemical and morphological features, plays a relevant physiological and pathological role in the organism, being pivotal in the maintenance of tissue development and homeostasis in the adult as well as in the regulation of immune responses. Deregulation of this process causes several human disorders including cancer, autoimmune and neurodegenerative diseases. Thus, modulation of the apoptotic process and of cell death in general, is a potential therapeutic approach for the treatment of several human pathologies

Modulating urban dynamics from a climate perspective – In-between spaces and climate neutrality

This contribution presents the results of a study that interprets in-between spaces as a modular system which structures space, relationships, and urban dynamics from a climate perspective. The aim is to demonstrate the positive contribution that technological-environmental design can offer in the context of redevelopment and new construction of the urban fabric, concerning the ecological performance of the entire urban system, particularly from the perspective of decarbonisation and climate mitigation. Within this research, a methodology for classifying and analysing in-between spaces was developed, as well as a method for evaluating the reduction of climate-altering emissions. The paper compares six case studies that represent the three identified categories of in-between spaces, evaluating them through the criteria of Naturalness, Proximity and Circularity and in relation to the six strategic axes of Green Cities.   Article info Received: 10/09/2023; Revised: 10/10/2023; Accepted: 19/10/202

Oil & Gas plant experience of Sub-Synchronous Torsional Interactions (SSTI) and operability optimization

Case Stud

Simulation and modelling for climate adaptation and mitigation. Experiences of environmental renovation in Rome

This paper defines an original methodological and applicative approach in support of the experimental/planning phase in the area of the regeneration of urban districts, in order to offer responses to the challenges of adapting to and mitigating climate change. Applied in two case studies in Rome, the methodology incorporates and verifies strategies and passive bioclimatic solutions through activities of ex-ante/ex-post modelling/simulation, constructing multicriteria and multiscalar planning models based on fluid dynamics, and measuring their effectiveness through the quantification of the reduction of CO2 emissions. The expected results are improved environmental comfort in outdoor, in-between, and indoor spaces, lower energy demand and CO2 emissions mitigation, through a set of actions and solutions that are comparable, replicable, and measurable in terms of energy-climate performance and environmental well-being

The action of CGRP and SP on cultured skin fibroblasts

Calcitonin gene-related peptide (CGRP) is the most abundant neuropeptide in the skin, followed by substance P (SP), vasoactive intestinal peptide (VIP), and other neuropeptides in smaller amounts. the proliferative effect of neuropeptides on fibroblasts may affect wound healing and may be associated with hyperproliferative skin and mesenchymal disorders. Understanding the neuropeptidergic action on fibroblasts may provide relevant information to a deeper comprehension of the healing process. This study reviews the action of the main neuropeptides, CGRP and SP, on cultured human skin fibroblasts.A systematic literature search was conducted on Medline and Web of Science databases on December 21, 2013.A total of 74 articles were retrieved using the proposed search strategies and 3 were found in the references section of the selected articles. Thirteen of the retrieved articles studied the action of CGRP and SP on cultured human skin fibroblasts, 12 of which related to SP and 1 related to both CGRP and SP.Only one study was retrieved about the action of both CGRP and SP on cultured human skin fibroblasts. Further studies are necessary to investigate CGRP on skin fibroblasts and its role in the fibroplasia phase of wound healing.Universidade Federal de São Paulo Unifesp, Dept Surg, Plast Surg Div, Postgrad Program Translat Surg, BR-04024002 São Paulo, BrazilUniv Estadual Santa Cruz, Dept Agr & Environm Sci, BR-45662900 Ilheus, BA, BrazilUniv Estadual Santa Cruz, Dept Biol Sci, BR-45662900 Ilheus, BA, BrazilUniversidade Federal de São Paulo Unifesp, Dept Surg, Plast Surg Div, Postgrad Program Translat Surg, BR-04024002 São Paulo, BrazilWeb of Scienc

Microstructural characterization of alumina-zirconia layered ceramics using positron annihilation spectroscopy

Positron annihilation spectroscopy (PAS), indentation, nanoindentation experiments and scanning electron microscopy (SEM) observations were performed on Al₂O₃-ZrO₂ laminates samples to assess the effect of residual stresses on their mechanical and microstructural properties. Layered samples were implemented by slip-casting, constituted by two thin Al₂O₃ external layers and an intermediate thick one, consisting of a mixture of Al₂O₃ and monoclinic ZrO₂ in the range 0-30 vol.%. In these systems residual tensile stresses fields were generated inside the external layers during cooling from the sintering temperature, by the expansion of the adjacent ZrO₂-containing layer. SEM observations showed the microstructural effects due to the level of tension related to the zirconia content. A correlation between the PAS parameters and the microstructural changes caused by the presence of residual stresses was found. Nanoindentation measurements were used to trace the sign and magnitude of the residual stress gradient across the interface between the layers.This work was supported by Spanish Government under Contract MAT2006-01038. The authors gratefully acknowledge the financial support from the Comunidad de Madrid and the Ministry of Education and Science of Spain, through the ESTRUMAT-CM (MAT/77) programs.Publicad

Relative expression of TAp73 and ΔNp73 isoforms

The transcription factor p73 belongs to the p53 family of tumour suppressors and similar to other family members, transcribed as different isoforms with opposing pro- and anti-apoptotic functions. Unlike p53, p73 mutations are extremely rare in cancers. Instead, the pro-apoptotic activities of transcriptionally active p73 isoforms are commonly inhibited by over-expression of the dominant negative p73 isoforms. Therefore the relative ratio of different p73 isoforms is critical for the cellular response to a chemotherapeutic agent. Here, we analysed the expression of N-terminal p73 isoforms in cell lines and mouse tissues. Our data showed that the transcriptionally competent TAp73 isoform is abundantly expressed in cancer cell lines compared to the dominant negative ΔNp73 isoform. Interestingly, we detected higher levels of ΔNp73 in some mouse tissues, suggesting that ΔNp73 may have a physiological role in these tissues

Obinutuzumab and miniCHOP for unfit patients with diffuse large B-cell lymphoma. A phase II study by Fondazione Italiana Linfomi

Objective: To evaluate activity and safety of obinutuzumab-miniCHOP (Ga101-miniCHOP) combination in older patients with Diffuse Large B-Cell Lymphoma (DLBCL) unfit to receive full dose immunochemotherapy. Materials and Methods: We conducted a Simon's two-stage phase II multicenter trial to investigate response rate (primary endpoint) and safety of six courses of Ga101-miniCHOP in older patients with DLBCL (≥65 years), prospectively defined as unfit according to a simplified Comprehensive Geriatric Assessment (sCGA). Results: Overall, 34 patients were enrolled (median age 82 years; range 68–89), with 27 out of the 33 eligible patients completing all six planned courses. Complete Remission (CR) rate was reported in fourteen patients (42%). After a median follow-up of sixteen months, the two-year Progression Free and Overall Survival (PFS and OS) were 49% (95% Confidence Interval (CI), 28 to 67) and 68% (95% CI, 49 to 81), respectively. The most frequent grade 3–4 adverse event was neutropenia in thirteen patients (26%). Conclusions: Based on the observed CR rate, study accrual was interrupted due to the very low probability of demonstrating the initial study hypothesis that Ga101-miniCHOP could improve results of historical data obtained with R-miniCHOP in this group of patients. Nonetheless, results achieved with the 33 treated patients confirm activity and good tolerability of the Ga101-miniCHOP regimen for older unfit adult patients with DLBCL

Are all cases of paediatric essential thrombocythaemia really myeloproliferative neoplasms? Analysis of a large cohort

Sporadic essential thrombocythaemia (ET) is rare in paediatrics, and the diagnostic and clinical approach to paediatric cases cannot be simply copied from experience with adults. Here, we assessed 89 children with a clinical diagnosis of ET and found that 23 patients (258%) had a clonal disease. The JAK2 V617F mutation was identified in 14 children, 1 child had the MPL W515L mutation, and 6 had CALR mutations. The monoclonal X-chromosome inactivation pattern was seen in six patients (two with JAK2 V617F and two with CALR mutations). The other 66 patients (742%) had persistent thrombocytosis with no clonality. There were no clinical or haematological differences between the clonal and non-clonal patients. The relative proportion of ET-specific mutations in the clonal children was much the same as in adults. The higher prevalence of nonclonal cases suggests that some patients may not have myeloproliferative neoplasms, with significant implications for their treatment