Pediatric liver diseases: current challenges and future perspectives

Chronic liver diseases in children represent a rising problem with significant effects on public health. In fact, several pediatric liver diseases are precursors of adult chronic hepatopathies, cirrhosis and hepatocellular carcinoma. The prevalence of liver diseases in children is unknown. In the USA, every year, 15,000 children are hospitalized for liver diseases, but these disorders continue to be under-recognized or diagnosed late. The main reason is due to the frequent absence of symptoms in the vast majority of liver diseases, especially in the early stages. In the last few decades several advances have been made in understanding the pathogenesis of liver diseases, permitting the discovery of new therapeutic targets to treat liver diseases, thus improving the natural history of these disorders. In this article we discuss the most recent advances in the understanding of the pathogenesis, diagnosis and treatment of the most frequent pediatric liver diseases

The Nitric Oxide Donor [Zn(PipNONO)Cl] Exhibits Antitumor Activity through Inhibition of Epithelial and Endothelial Mesenchymal Transitions

Simple Summary Nitric oxide (NO) plays a critical pathophysiological role in cancer by modulating several processes, such as angiogenesis, tumor growth, and metastatic potential. The aim of this study was to characterize the antitumor effects of a novel NO donor, [Zn(PipNONO)Cl], on the processes of epithelial- and endothelial-mesenchymal transitions (EMT and EndMT), known to actively participate in cancer progression. Two tumor cells lines were used in this study: human lung cancer cells (A549) and melanoma cells (A375), alone and co-cultured with human endothelial cells. Our results demonstrate that both tumor and endothelial cells were targets of NO action, which impaired EMT and EndMT functional and molecular features. Further studies are needed to finalize the therapeutic use of the novel NO donor. Exogenous nitric oxide appears a promising therapeutic approach to control cancer progression. Previously, a nickel-based nonoate, [Ni(SalPipNONO)], inhibited lung cancer cells, along with impairment of angiogenesis. The Zn(II) containing derivatives [Zn(PipNONO)Cl] exhibited a protective effect on vascular endothelium. Here, we have evaluated the antitumor properties of [Zn(PipNONO)Cl] in human lung cancer (A549) and melanoma (A375) cells. Metastasis initiates with the epithelial-mesenchymal transition (EMT) process, consisting of the acquisition of invasive and migratory properties by tumor cells. At not cytotoxic levels, the nonoate significantly impaired A549 and A375 EMT induced by transforming growth factor-beta 1 (TGF-beta 1). Reduction of the mesenchymal marker vimentin, upregulated by TGF-beta 1, and restoration of the epithelial marker E-cadherin, reduced by TGF-beta 1, were detected in both tumor cell lines in the presence of Zn-nonoate. Further, the endothelial-mesenchymal transition achieved in a tumor-endothelial cell co-culture was assessed. Endothelial cells co-cultured with A549 or A375 acquired a mesenchymal phenotype with increased vimentin, alpha smooth muscle actin and Smad2/3, and reduced VE-cadherin. The presence of [Zn(PipNONO)Cl] maintained a typical endothelial phenotype. In conclusion, [Zn(PipNONO)Cl] appears a promising therapeutic tool to control tumor growth and metastasis, by acting on both tumor and endothelial cells, reprogramming the cells toward their physiologic phenotypes

Livingscape: A Multi-sensory Approach to Improve the Quality of Urban Spaces

The urban environmental quality of two districts in Turin was studied through a livingscape approach, involving an integrated subjective and objective field analysis of soundscape, lightscape, thermalscape and airscape. Aspect such as pleasantness, calmness and vibrancy were investigated. The analysis was aimed at comparing the results which were found for the two districts, with the goal of validating this methodology to be used for the requalification of the areas, through the identification of pleasant and unpleasant urban areas using criteria other than the ones that are currently adopted by specialists and which have a limited relevance on open space comfort

Clinical outcomes under hydroxyurea treatment in polycythemia vera: a systematic review and meta-analysis

H ydroxyurea is the standard treatment in high-risk patients with polycythemia vera. However, estimates of its effect in terms of clinical outcomes (thrombosis, bleeding, hematologic transformations and mortality) are lacking. We performed a meta-analysis to determine the absolute risk of events in recent cases of patients under hydroxyurea treatment. We searched for relevant articles or abstracts in the following databases: Medline, EMBASE, clinicaltrials.gov, WHO International Clinical Trials Registry, LILACS. Sixteen studies published from 2008 to 2018 reporting number of events using World Health Organization diagnosis for polycythemia vera were selected. Through a random effect logistic model, incidences, study heterogeneity and confounder effects were estimated for each outcome at different follow ups. Overall, 3,236 patients were analyzed. While incidences of thrombosis and acute myeloid leukemia were stable over time, mortality and myelofibrosis varied depending on followup duration. Thrombosis rates were 1.9%, 3.6% and 6.8% persons/year at median ages 60, 70 and 80 years, respectively. Higher incidence of arterial events was predicted by previous cardiovascular complication. Leukemic transformation incidence was 0.4% persons/year. Incidence of transformation to myelofibrosis and mortality were significantly dependent on age and follow-up duration. For myelofibrosis, rates were 5.0 at five years and 33.7% at ten years; overall mortality was 12.6% and 56.2% at five and ten years, respectively. In conclusion, we provide reliable risk estimates for the main outcomes in polycythemia vera patients under hydroxyurea treatment. These findings can help design comparative clinical trials with new cytoreductive drugs and prove the feasibility of using critical end points for efficacy, such as major thrombosis

Behind the scenes: How RNA orchestrates the epigenetic regulation of gene expression

Non-coding DNA accounts for approximately 98.5% of the human genome. Once labeled as “junk DNA”, this portion of the genome has undergone a progressive re-evaluation and it is now clear that some of its transcriptional products, belonging to the non-coding RNAs (ncRNAs), are key players in cell regulatory networks. A growing body of evidence demonstrates the crucial impact of regulatory ncRNAs on mammalian gene expression. Here, we focus on the defined relationship between chromatin-interacting RNAs, particularly long non-coding RNA (lncRNA), enhancer RNA (eRNA), non-coding natural antisense transcript (ncNAT), and circular RNA (circRNA) and epigenome, a common ground where both protein and RNA species converge to regulate cellular functions. Through several examples, this review provides an overview of the variety of targets, interactors, and mechanisms involved in the RNA-mediated modulation of loci-specific epigenetic states, a fundamental evolutive strategy to orchestrate mammalian gene expression in a timely and reversible manner. We will discuss how RNA-mediated epigenetic regulation impacts development and tissue homeostasis and how its alteration contributes to the onset and progression of many different human diseases, particularly cancer

Numerical simulation of tanks containing pressurized gas exposed to accidental fires: Evaluation of the transient heat up

Fires may impact on process and storage equipment causing severe damages and potential accident escalation. In the present study, a Computational Fluid Dynamics (CFD) model was set up for pressurized vessels exposed to accidental fires, aimed at determining the transient behaviour of the stored fluid during the heat-up. The model was developed for vessels containing pressurized flammable gases, such as methane, propane and hydrogen. The ANSYS FLUENT software was used in order to implement a twodimensional circular geometry considering a medium scale spherical tanker. The presence of a heat resistant coating was considered in the analysis. The model allowed predicting the velocity and temperature profiles, thus obtaining the pressurization rate in the vessel and providing key indications for the evaluation of the vessel resistance

Scoping Review on Platelets and Tumor Angiogenesis: Do We Need More Evidence or Better Analysis?

Platelets are an active component of the tumor microenvironment (TME), involved in the regulation of multiple tumor processes, including angiogenesis. They are generated rich in angiogenic factors in their granules to actively participate in the hemostatic process by megakaryocytes and further enriched in angiogenic factors by all components of the tumor microenvironment to control the angiogenic process because of their preferential relationship with the endothelial component of vessels. In recent decades, the literature has reported a great deal of evidence on the role of platelets in tumor angiogenesis; however, it is unclear whether the number or mean volume of platelets and/or their content and localization in TME may have clinical relevance in the choice and management of therapy for the cancer patient. In this scoping review, we collected and critically reviewed the scientific evidence supporting a close relationship between platelets, cancer, and angiogenesis. The aim of this work was to define the landscape of platelet-activated angiogenesis in cancer progression and analyze what and how much evidence is present in the last 20 years in the literature at both the preclinical and clinical levels, to answer whether platelets could be a useful determinant for analyzing tumor angiogenesis. In conclusion, this scoping review indicates that there is much evidence, both preclinical and clinical, but in the preclinical context, studies demonstrate the direct involvement of platelets in tumor angiogenesis; in the clinical context the evidence is indirect, though strong, and the indication of how and to what extent platelet content contributes to tumor angiogenesis is lacking. So, do we need more evidence or better analysis? More molecular and quali-quantitative data is needed to translate the results obtained in preclinical studies into the clinical setting. This information about platelets, if correlated with tumor type and its biology, including tumor vasculature, type of angiogenesis, and patient characteristics (age, sex, comorbidities, drug treatments for chronic diseases) could be an important pa- rameter for correlating platelet biology to angiogenesis, for personalizing cancer therapy, and for clinical prognosis

Livingscape multi-sensory experience in urban historical places: subjective assessment from the local people and quality of the urban environment

The environmental quality of open spaces has more and more become an essential part of urban culture. The multi-sensory nature of livingscape (urban blight, soundscape, light-scape, thermal-scape, subjective user responses) assessments is acknowledged by a case study whereby the response to the sound is also based upon other sensory and behavioral elements, rather than the sound per se. Subjective environmental perceptions and objective measures (addressing acoustical, lighting and thermal parameters) data were collected in St. Salvario, an historical district in Turin, during summer 2010 and winter 2011. From an historical analysis thirteen key-spaces were selected on site which characterize past and present soundscape of the district subdivided in nodes, paths and borders. In this work only a part of the overall study is presented. Thirteen factors were singled out from the factorial analysis on environmental data collected in situ based on 33 measurement parameters. Significant correlation (p-values<0.01) among the thirteen factors and the subjective items related to environmental perception and pleasantness related to day/night-time and summer/winter period were carried out. I plots related to day/night-time and summer/winter period lightize the key-spaces behaviors for the different environmental factors and the pleasantness answers emerging from the questionnaires. Research aim to identify how the two approaches, quantitative and qualitative, and the types of knowledge produced by each, can be effectively used side by side and integrated effectively into policy and practice

Livingscape approach to improve urban historical places

This work presents a study on "urban quality" as an important support to urban planning and management which was carried out through the livingscape approach (urban blight, soundscape, light-scape, thermal-scape, questionnaires) within the historic district „San Salvario‟ in Turin. To account for the multidimensional character of the urban quality in towns, an integrated analysis of three aspects was addressed, involving: 1) psychometric tools to measure the perception of environmental quality; 2) different aspects related to the urban blight (both in architectural and environmental terms); 3) objective investigation of environmental quality through the measurement of acoustic, visual, thermal and IAQ physical parameters. In particular, the paper focuses on the correlations among environmental perception subjective data and urban blight factors. Subjective and objective data were collected in-the-field during summer 2010 and winter 2011 every 30 m along 13 key-spaces of the district. The urban blight‟s survey was filled by some experts, while the environmental perception was delineated through the analysis of 496 questionnaires (240 in summer and 256 in winter), submitted to the users of the area during the measurements. An overview of the procedure and of some results which were found is presented