Capillary extrusion behavior of phenolphthalein poly(ether-ether-sulphone) (PES-C)

The capillary extrusion flow properties of novel engineering thermoplastic phenolphthalein poly(ether-ether-sulphone) (PES-C) have been investigated using capillary rheometer. The dependence of viscosity on the wall shear rate and temperatures were obtained. The flow activation energy was found to decrease with shear rate but to be constant with shear stress. The entrance effect was calculated and from which the extensional behavior was estimated using Cogswell's method. From the extrudate swell ratio the principal normal stress was evaluated and a temperature-independent correlation was observed when they were plotted against shear stress. The melt fracture phenomena were checked and discussed also. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 65:951–958, 1997     

Controlled Mesoporosity in SiOC via Chemically Bonded Polymeric “Spacers”

Silicon oxycarbides with controlled porosity in the mesopore range have been obtained through high‐temperature pyrolysis of newly developed reactive siloxane formulations. The starting gels have been synthesized via Pt catalyzed hydrosilylation reaction between polyhydromethylsiloxane (PHMS) and vinyl‐terminated polydimethylsiloxane (PDMS) of different molecular weights in the presence of tetravinyltetramethylcyclotetrasiloxane as a crosslinking enhancer. In our approach, the PDMS serves the double purpose of size‐controlling templating agent as well as solvent at the early stages of the synthesis. During the curing step, the vinyl‐terminated PDMS is chemically bonded to the preceramic network through the extremely efficient hydrosilylation reaction and “solidify.” Accordingly, its removal during pyrolysis occurs through decomposition of a solid phase with retention of the formed porosity. The structural and morphological evolution of the preceramic gels containing the molecular spacers have been investigated as a function of the thermal treatment temperature by N₂ physisorption measurements, thermogravimetry, and SEM analyses. The results show that the pore size distribution of the resulting SiOCs depends on the molecular weight of the PDMS and is directly related to the molecular volume assumimg that the PDMS chains are entangled into spheroidal shapes. The total pore volume is related to the initial amount of templating PDMS assuming its complete decomposition during pyrolysis.     

Wooden window frames with structural sealants: manufacturing improvements and experimental validation of a finite element model

This paper proposes a finite element (FE) model of a novel wooden window frame typology and validates it by experimental tests on window frames and corner joint specimens. The innovation consists of the application of the structural silicone sealant only at the interface between wood and one of the thin glass layers of the double-glazing glass, so achieving a low application depth. This technique reduces the sealant quantity and allows the disassembly and substitution of the glass from the frame in case of breakage. In order to inform the FE model of the whole frame, the dowelled butt corner joint strength is measured by specific experimental tests. The results show a good correlation between the FE model and the experimental results in the range of small frame deformations, which are of interest for the proposed application. In particular, the FE curve overestimates the bottom corner displacement of about 17% at 1000?N load, 7% at 2000?N and less than 5% at higher applied force on the upper corner. The model is then applied to various wooden frame geometries in order to evaluate if the proposed silicone application mode and dowelled corner joints type allow an acceptable stiffness of the frame, and, in particular, low deformations of the bottom corner joint, in order to maintain the wooden frame functionality when subject to external loads. The approach could be useful when assessing optimal sealing application modes, wood-sealant-glass joint geometries, corner joint geometries and window frame geometries to limit the bottom corner joint deformation within the required technical specifications.     

The L467F-F508del Complex Allele Hampers Pharmacological Rescue of Mutant CFTR by Elexacaftor/Tezacaftor/Ivacaftor in Cystic Fibrosis Patients: The Value of the Ex Vivo Nasal Epithelial Model to Address Non-Responders to CFTR-Modulating Drugs

Loss-of-function mutations of the CFTR gene cause cystic fibrosis (CF) through a variety of molecular mechanisms involving altered expression, trafficking, and/or activity of the CFTR chloride channel. The most frequent mutation among CF patients, F508del, causes multiple defects that can be, however, overcome by a combination of three pharmacological agents that improve CFTR channel trafficking and gating, namely, elexacaftor, tezacaftor, and ivacaftor. This study was prompted by the evidence of two CF patients, compound heterozygous for F508del and a minimal function variant, who failed to obtain any beneficial effects following treatment with the triple drug combination. Functional studies on nasal epithelia generated in vitro from these patients confirmed the lack of response to pharmacological treatment. Molecular characterization highlighted the presence of an additional amino acid substitution, L467F, in cis with the F508del variant, demonstrating that both patients were carriers of a complex allele. Functional and biochemical assays in heterologous expression systems demonstrated that the double mutant L467F-F508del has a severely reduced activity, with negligible rescue by CFTR modulators. While further studies are needed to investigate the actual prevalence of the L467F-F508del allele, our results suggest that this complex allele should be taken into consideration as plausible cause in CF patients not responding to CFTR modulators.     

Effects of Eltrombopag on In Vitro Macrophage Polarization in Pediatric Immune Thrombocytopenia

Immune Thrombocytopenia (ITP) is an autoimmune disease characterized by autoantibodies-mediated platelet destruction, a prevalence of M1 pro-inflammatory macrophage phenotype and an elevated T helper 1 and T helper 2 lymphocytes (Th1/Th2) ratio, resulting in impairment of inflammatory profile and immune response. Macrophages are immune cells, present as pro-inflammatory classically activated macrophages (M1) or as anti-inflammatory alternatively activated macrophages (M2). They have a key role in ITP, acting both as effector cells, phagocytizing platelets, and, as antigen presenting cells, stimulating auto-antibodies against platelets production. Eltrombopag (ELT) is a thrombopoietin receptor agonist licensed for chronic ITP to stimulate platelet production. Moreover, it improves T and B regulatory cells functions, suppresses T-cells activity, and inhibits monocytes activation. We analyzed the effect of ELT on macrophage phenotype polarization, proposing a new possible mechanism of action. We suggest it as a mediator of macrophage phenotype switch from the M1 pro-inflammatory type to the M2 anti-inflammatory one in paediatric patients with ITP, in order to reduce inflammatory state and restore the immune system function. Our results provide new insights into the therapy and the management of ITP, suggesting ELT also as immune-modulating drug.     

Different Stages of Quiescence,Senescence, and Cell Stress Identified by Molecular Algorithm Based on the Expression of Ki67, RPS6, and Beta-Galactosidase Activity

During their life span, cells have two possible states: a non-cycling, quiescent state (G0) and a cycling, activated state. Cells may enter a reversible G0 state of quiescence or, alternatively, they may undergo an irreversible G0 state. The latter may be a physiological differentiation or, following a stress event, a senescent status. Discrimination among the several G0 states represents a significant investigation, since quiescence, differentiation, and senescence are progressive phenomena with intermediate transitional stages. We used the expression of Ki67, RPS6, and beta-galactosidase to identify healthy cells that progressively enter and leave quiescence through G0-entry, G0 and G0-alert states. We then evaluated how cells may enter senescence following a genotoxic stressful event. We identified an initial stress stage with the expression of beta-galactosidase and Ki67 proliferation marker. Cells may recover from stress events or become senescent passing through early and late senescence states. Discrimination between quiescence and senescence was based on the expression of RPS6, a marker of active protein synthesis that is present in senescent cells but absent in quiescent cells. Even taking into account that fixed G0 states do not exist, our molecular algorithm may represent a method for identifying turning points of G0 transitional states that continuously change.     

The Emerging Role of Presepsin (P-SEP) in the Diagnosis of Sepsis in the Critically Ill Infant: A Literature Review

Sepsis causes high rates of morbidity and mortality in NICUs. The estimated incidence varies between 5 and 170 per 1000 births, depending on the social context. In very low birth-weight neonates, the level of mortality increases with the duration of hospitalization, reaching 36% among infants aged 8–14 days and 52% among infants aged 15–28 days. Early diagnosis is the only tool to improve the poor prognosis of neonatal sepsis. Blood culture, the gold standard for diagnosis, is time-consuming and poorly sensitive. C-reactive protein and procalcitonin, currently used as sepsis biomarkers, are influenced by several maternal and fetal pro-inflammatory conditions in the perinatal age. Presepsin is the N-terminal fragment of soluble CD14 subtype (sCD14-ST): it is released in the bloodstream by monocytes and macrophages, in response to bacterial invasion. Presepsin seems to be a new, promising biomarker for the early diagnosis of sepsis in neonates as it is not modified by perinatal confounding inflammatory factors. The aim of the present review is to collect current knowledge about the role of presepsin in critically ill neonates.