Pumice and lapillus scraps: New national environmental-friendly chance for the production of ceramic tiles

Italian pumice and volcanic lapillus scraps have been used in different percentages as alternative raw materials to foreign feldspars in porcelain stoneware mixtures. The aim of this work was to create naturally colored support to limit the use of artificial dyes while maintaining the technical properties of the reference product. For this purpose, the significant presence of chromophores (Fe and Ti in particular) in by-products from extraction of Italian volcanic pumice and lapillus was exploited. The work was carried out in collaboration with a company: the products were made on a laboratory scale and then they were glazed and fired within the industrial production cycle (48 min, 1210 ◦C). The resulting slip and the fired samples were characterized by measuring the efflux time, density, linear shrinkage, water absorption and tensile strength to evaluate the technological performance. In addition, thermogravimetric analysis (TG), differential thermal analysis (DTA), and optical and mechanical dilatometry were performed to study the thermal behavior of the formulations. The obtained products could be classified as porcelain stoneware and belong to the BIa group (WA 0.5%, B. S.>35 MPa) in accordance with UNI EN 14411 ISO 13006

New Perspective in HCV Clinical and Economical Management of the Current and Future Therapies

Hepatitis C virus (HCV) is a progressive disease that infects more than 185 million individuals worldwide and is associated with persistence of viral replication and ongoing necroinflammation and fibrosis. To date 20% of patients chronically infected with HCV progress to cirrhosis. Epidemiological studies demonstrate that the incidence of HCV is not well known, because acute infection is generally asymptomatic. The global prevalence is about 2.2% and there is a large degree of geographic variability. Before the 2011, the gold standard of therapy for the treatment of chronic hepatitis C (CHC) was based on the combination of pegylated Interferon (peg-IFN) and Ribavirin (RBV). However, several aspects related to safety profile limited their use in clinical practice. In the recent years, thanks to basic research on HCV structure and replicative cycle, it has been possible to develop direct acting antiviral drugs that have dramatically increased the viral clearance rate. Specifically, the advent of the triple therapy employing direct acting antivirals has dramatically increased the viral clearance rate, from less than 10%, with the initial regimen of IFN monotherapy, to more than 95% with the current therapy. Even though new medications for hepatitis C are effective disease modifiers and have the potential, in a long term perspective, to eradicate the pathology, the cost of new treatments are unlikely to be sustainable for the NHSs. The evidence documenting the effectiveness and tolerability of the new therapies for HCV and several pharmacoeconomic analysis, shows that despite the cost, the new treatments can be considered cost-effective in the long period. However, the health care systems are unable to compensate the height financial resources immediately needed for treating patients with the long terms savings that will be obtained from the eradication of HCV. Indeed, new pharmaceutical policy and a global commitment is required to improve strategies of treatment and price negotiation with pharmaceutical companies to move from a theoretical cost-effectiveness approach to a practical cost-sustainable reality

Influence of drying conditions on the acacia gum particle growth in fluidized bed agglomeration: in-line monitoring of particle size

[EN] Acacia gum is an important food emulsifier that presents poor instant properties which can be improved by fluidized bed agglomeration. This study investigated the influence of drying conditions on particle growth kinetics using an in-line particle size monitoring by spatial filter velocimetry. The drying conditions varied according to the binder flow rate and the fluidizing air temperature. The particle growth kinectis showed drying conditions dependence. At mild drying conditions the growth rate and the process yield were higher. The in-line particle size monitoring was useful to observe the influence of the drying conditions on the growth kinetics.Rosa, J.; Nascimento, RF.; Andreola, K.; Taranto, OP. (2018). Influence of drying conditions on the acacia gum particle growth in fluidized bed agglomeration: in-line monitoring of particle size. En IDS 2018. 21st International Drying Symposium Proceedings. Editorial Universitat Politècnica de València. 1439-1446. https://doi.org/10.4995/IDS2018.2018.7345OCS1439144

The role of RIPK1 mediated cell death in acute on chronic liver failure

Acute-on-chronic liver failure (ACLF) is characterized predominantly by non-apoptotic forms of hepatocyte cell death. Necroptosis is a form of programmed lytic cell death in which receptor interacting protein kinase (RIPK) 1, RIPK3 and phosphorylated mixed lineage kinase domain-like (pMLKL) are key components. This study was performed to determine the role of RIPK1 mediated cell death in ACLF. RIPK3 plasma levels and hepatic expression of RIPK1, RIPK3, and pMLKL were measured in healthy volunteers, stable patients with cirrhosis, and in hospitalized cirrhotic patients with acutely decompensated cirrhosis, with and without ACLF (AD). The role of necroptosis in ACLF was studied in two animal models of ACLF using inhibitors of RIPK1, necrostatin-1 (NEC-1) and SML2100 (RIPA56). Plasma RIPK3 levels predicted the risk of 28- and 90-day mortality (AUROC, 0.653 (95%CI 0.530–0.776), 0.696 (95%CI 0.593–0.799)] and also the progression of patients from no ACLF to ACLF [0.744 (95%CI 0.593–0.895)] and the results were validated in a 2nd patient cohort. This pattern was replicated in a rodent model of ACLF that was induced by administration of lipopolysaccharide (LPS) to bile-duct ligated rats and carbon tetrachloride-induced fibrosis mice administered galactosamine (CCL4/GalN). Suppression of caspase-8 activity in ACLF rodent model was observed suggesting a switch from caspase-dependent cell death to necroptosis. NEC-1 treatment prior to administration of LPS significantly reduced the severity of ACLF manifested by reduced liver, kidney, and brain injury mirrored by reduced hepatic and renal cell death. Similar hepato-protective effects were observed with RIPA56 in a murine model of ACLF induced by CCL4/GalN. These data demonstrate for the first time the importance of RIPK1 mediated cell death in human and rodent ACLF. Inhibition of RIPK1 is a potential novel therapeutic approach to prevent progression of susceptible patients from no ACLF to ACLF

Circulating microRNAs Reveal Time Course of Organ Injury in a Porcine Model of Acetaminophen-Induced Acute Liver Failure

Acute liver failure is a rare but catastrophic condition which can progress rapidly to multi-organ failure. Studies investigating the onset of individual organ injury such as the liver, kidneys and brain during the evolution of acute liver failure, are lacking. MicroRNAs are short, non-coding strands of RNA that are released into the circulation following tissue injury. In this study, we have characterised the release of both global microRNA and specific microRNA species into the plasma using a porcine model of acetaminophen-induced acute liver failure. Pigs were induced to acute liver failure with oral acetaminophen over 19h±2h and death occurred 13h±3h thereafter. Global microRNA concentrations increased 4h prior to acute liver failure in plasma (P<0.0001) but not in isolated exosomes, and were associated with increasing plasma levels of the damage-associated molecular pattern molecule, genomic DNA (P<0.0001). MiR122 increased around the time of onset of acute liver failure (P<0.0001) and was associated with increasing international normalised ratio (P<0.0001). MiR192 increased 8h after acute liver failure (P<0.0001) and was associated with increasing creatinine (P<0.0001). The increase in miR124-1 occurred concurrent with the pre-terminal increase in intracranial pressure (P<0.0001) and was associated with decreasing cerebral perfusion pressure (P<0.002)

Extracorporeal liver assist device to exchange albumin and remove endotoxin in acute liver failure: Results of a pivotal pre-clinical study

Background & AimsIn acute liver failure, severity of liver injury and clinical progression of disease are in part consequent upon activation of the innate immune system. Endotoxaemia contributes to innate immune system activation and the detoxifying function of albumin, critical to recovery from liver injury, is irreversibly destroyed in acute liver failure. University College London-Liver Dialysis Device is a novel artificial extracorporeal liver assist device, which is used with albumin infusion, to achieve removal and replacement of dysfunctional albumin and reduction in endotoxaemia. We aimed to test the effect of this device on survival in a pig model of acetaminophen-induced acute liver failure.MethodsPigs were randomised to three groups: Acetaminophen plus University College London-Liver Dialysis Device (n=9); Acetaminophen plus Control Device (n=7); and Control plus Control Device (n=4). Device treatment was initiated two h after onset of irreversible acute liver failure.ResultsThe Liver Dialysis Device resulted in 67% reduced risk of death in acetaminophen-induced acute liver failure compared to Control Device (hazard ratio=0.33, p=0.0439). This was associated with 27% decrease in circulating irreversibly oxidised human non-mercaptalbumin-2 throughout treatment (p=0.046); 54% reduction in overall severity of endotoxaemia (p=0.024); delay in development of vasoplegia and acute lung injury; and delay in systemic activation of the TLR4 signalling pathway. Liver Dialysis Device-associated adverse clinical effects were not seen.ConclusionsThe survival benefit and lack of adverse effects would support clinical trials of University College London-Liver Dialysis Device in acute liver failure patients

Comparative life cycle environmental and economic assessment of anaerobic membrane bioreactor and disinfection for reclaimed water reuse in agricultural irrigation: A case study in Italy

Supplementary data are available online at https://www.sciencedirect.com/science/article/pii/S0959652621004212#appsec1 .Reuse of treated wastewater for irrigation purposes is a measure to reduce water stress and overexploitation of freshwater resources. This study aims to investigate the environmental and economic impacts of a current conventional wastewater treatment plant (WWTP) in Peschiera Borromeo (Milan, Italy), and compare possible scenarios to enable reclaimed water reuse for agriculture. Accordingly, we propose alternative disinfection methods (i.e. enhanced UV, peracetic acid) and replace conventional activated sludge (CAS) with upflow anaerobic sludge blanket (UASB) for biological treatment and use anaerobic membrane bioreactor (AnMBR) as the tertiary treatment. Life cycle assessment (LCA) and life cycle costing (LCC) were implemented on the existing full-scale wastewater treatment line and the hypothetical scenarios. In most cases, the impact categories are primarily influenced by fertilizer application and direct emissions to water (i.e. nutrients and heavy metals). The baseline scenario appears to have the largest environmental impact, except for freshwater eutrophication, human ecotoxicity and terrestrial ecotoxicity. As expected, water depletion is the most apparent impact category between the baseline and proposed scenarios. The UASB + AnMBR scenario gives relatively higher environmental benefits than the other proposed scenarios in climate change (−28%), fossil fuel depletion (−31%), mineral resource depletion (−52%), and terrestrial ecotoxicity compared to the baseline. On the other hand, the highest impact on freshwater eutrophication is also obtained by this scenario since the effluent from the anaerobic processes is rich in nutrients. Moreover, investment and operational costs vary remarkably between the scenarios, and the highest overall costs are obtained for the UASB + AnMBR line mostly due to the replacement of membrane modules (24% of the total cost). The results highlighted the importance of the life cycle approach to support decision making when considering possible upgrading scenarios in WWTPs for water reuse.This study was carried out within the framework of the ‘Digital-Water.City - DWC’ Innovation Action which has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 820954. Alessia Foglia kindly acknowledges the Fondazione Cariverona for funding her PhD scholarship

Cell death markers in cirrhotic patients with acute decompensation

The aims of this study were to determine the role of cell death in cirrhotic patients with acute decompensation (AD) and acute on chronic liver failure (ACLF) using plasma-based biomarkers. The patients studied were part of the CANONIC study (N=337; AD: 258; ACLF: 79); additional cohorts included healthy volunteers, stable cirrhotic patients and a group of 16 AD patients for histological studies. Caspase-cleaved keratin 18 (cK18) and keratin 18 (K18), which reflect apoptotic and total cell death respectively and cK18:K18 ratio (apoptotic index) were measured in the plasma by ELISA. The concentrations of cK18 and K18 increased and the cK18:K18 ratio decreased with increasing severity of AD and ACLF (p<0.001 respectively). Alcohol etiology, no previous decompensation and alcohol abuse were associated with increased cell death markers whereas underlying infection was not. Close correlation was observed between the cell death markers and, markers of systemic inflammation, hepatic failure, alanine amino transferase and bilirubin but not with markers of extra hepatic organ injury. TUNEL staining confirmed evidence of greater hepatic cell death in patients with ACLF as opposed to AD. Inclusion of cK18 and K18 improved the performance of the CLIF-C AD score in prediction of progression from AD to ACLF (p<0.05). CONCLUSION: Cell death, likely hepatic, is an important feature of AD and ACLF and its magnitude correlates with clinical severity. Non-apoptotic forms of cell death predominate with increasing severity of AD and ACLF. The data suggests that ACLF is a heterogeneous entity and shows that the importance of cell death in its pathophysiology is dependent on predisposing factors, precipitating illness, response to injury and the type of organ failure. This article is protected by copyright. All rights reserved

Potential antiviral effects of pantethine against SARS-CoV-2

Abstract SARS-CoV-2 interacts with cellular cholesterol during many stages of its replication cycle. Pantethine was reported to reduce total cholesterol levels and fatty acid synthesis and potentially alter different processes that might be involved in the SARS-CoV-2 replication cycle. Here, we explored the potential antiviral effects of pantethine in two in vitro experimental models of SARS-CoV-2 infection.Pantethine reduced the infection of cells by SARS-CoV-2 in both preinfection and postinfection treatment regimens. Accordingly, cellular expression of the viral spike and nucleocapsid proteins was substantially reduced, and we observed a significant reduction in viral copy numbers in the supernatant of cells treated with pantethine. In addition, pantethine inhibited the infection-induced increase in TMPRSS2 and HECT E3 ligase expression in infected cells as well as the increase in antiviral interferon-beta response and inflammatory gene expression in Calu-3a cells. Our results demonstrate that pantethine, which is well tolerated in humans, was very effective in controlling SARS-CoV-2 infection and might represent a new therapeutic drug that can be repurposed for the prevention or treatment of COVID-19 and long COVID syndrome

MUC4 and MUC5AC are highly specific tumour-associated mucins in biliary tract cancer

Alterations in epithelial mucin expression are associated with carcinogenesis, but there are few data in biliary tract cancer (BTC). In pancreatic malignancy, MUC4 is a diagnostic and prognostic tumour marker, whereas MUC5AC has been proposed as a sensitive serological marker for BTC. We assessed MUC4 and MUC5AC expression in (i) prospectively collected bile and serum specimens from 72 patients with biliary obstruction (39 BTC) by real-time reverse transcriptase–PCR (qPCR) and western blot analysis, and (ii) 79 archived biliary tissues (69 BTC) by immunohistochemistry. In bile, MUC4 protein was detected in 27% of BTC and 29% of primary sclerosing cholangitis (PSC) cases, but not in other benign and malignant biliary diseases (P<0.01 and P=0.06). qPCR revealed a 1.9-fold increased MUC4 mRNA expression in BTC patients' bile compared with benign disease. In archived tissues, MUC4 protein was detected in 37% of BTC but in none of the benign samples (P=0.03). In serum, MUC5AC was found exclusively in BTC and PSC sera (44% and 13%, respectively; P<0.001 for BTC vs non-BTC) and correlated negatively with BTC survival. Biliary MUC4 and serum MUC5AC are highly specific tumour-associated mucins that may be useful in the diagnosis and formulation of therapeutic strategies in BTC