The Association of Il28b Genotype with the Histological Features of Chronic Hepatitis C Is HCV Genotype Dependent

The interleukin 28B (IL28B) rs12979860 polymorphism is associated with treatment outcome in hepatitis C virus (HCV) genotype 1 and 4 patients. Its association with the histological features of chronic hepatitis C and disease severity needs further clarifications. To assess the correlation between IL28B genotype, HCV genotype and liver biopsy findings in untreated patients.

Materials and Methods

Pre-treatment liver biopsies from 335 HCV Caucasian patients (59% males, age 50 years) enrolled in the MIST study were staged for fibrosis and inflammation according to the METAVIR and the Ishak scoring systems; steatosis was dichotomized as <5% or ≥5%. IL28B was typed by Taqman Single Nucleotide Polymorphism (SNP) genotyping assay. HCV genotype was 1 in 151 (45%), 2 in 99 (30%), 3 in 50 (15%) and 4 in 35 (10%) patients. IL28B genotype was CC in 117 (34%), CT in 166 (49%) and TT in 52 (15%). At univariate analysis, the IL28B CC genotype was associated with severe portal inflammation in HCV-1 patients (CC vs. CT/TT: 86% vs. 63%, p = 0.005), severe lobular inflammation in HCV-2 patients (CC vs. CT/TT: 44% vs. 23%, p = 0.03), and less fatty infiltration in HCV-1 patients (CC vs. CT/TT: 72% vs. 51%, p = 0.02). Despite the lack of any association between IL28B and fibrosis stage, in HCV-3 patients IL28B CC correlated with METAVIR F3–F4 (CC vs. CT/TT: 74% vs. 26%, p = 0.05). At multivariate analysis, the genotype CC remained associated with severe portal inflammation in HCV-1, only (Odds Ratio (OR): 95% Confidence Interval (CI): 3.24 (1.23–8.51)). IL28B genotype is associated with the histological features of chronic hepatitis C in a HCV genotype dependent manner, with CC genotype being independently associated with severe portal inflammation.     

Controlling the Er content of porous silicon using the doping current intensity

The results of an investigation on the Er doping of porous silicon are presented. Electrochemical impedance spectroscopy, optical reflectivity, and spatially resolved energy dispersive spectroscopy (EDS) coupled to scanning electron microscopy measurements were used to investigate on the transient during the first stages of constant current Er doping. Depending on the applied current intensity, the voltage transient displays two very different behaviors, signature of two different chemical processes. The measurements show that, for equal transferred charge and identical porous silicon (PSi) layers, the applied current intensity also influences the final Er content. An interpretative model is proposed in order to describe the two distinct chemical processes. The results can be useful for a better control over the doping process.

PACS

81.05.Rm; 82.45.Rr     

Novel Simple Conjugation Chemistries for Decoration of GMMA with Heterologous Antigens

Outer Membrane Vesicles (OMV) constitute a promising platform for the development of efficient vaccines. OMV can be decorated with heterologous antigens (proteins or polysaccharides), becoming attractive novel carriers for the development of multicomponent vaccines. Chemical conjugation represents a tool for linking antigens, also from phylogenetically distant pathogens, to OMV. Here we develop two simple and widely applicable conjugation chemistries targeting proteins or lipopolysaccharides on the surface of Generalized Modules for Membrane Antigens (GMMA), OMV spontaneously released from Gram-negative bacteria mutated to increase vesicle yield and reduce potential reactogenicity. A Design of Experiment approach was used to identify optimal conditions for GMMA activation before conjugation, resulting in consistent processes and ensuring conjugation efficiency. Conjugates produced by both chemistries induced strong humoral response against the heterologous antigen and GMMA. Additionally, the use of the two orthogonal chemistries allowed to control the linkage of two different antigens on the same GMMA particle. This work supports the further advancement of this novel platform with great potential for the design of effective vaccines.     

Chemical Modeling of Acid-Base Properties of Soluble Biopolymers Derived from Municipal Waste Treatment Materials

This work reports a study of the proton-binding capacity of biopolymers obtained from different materials supplied by a municipal biowaste treatment plant located in Northern Italy. One material was the anaerobic fermentation digestate of the urban wastes organic humid fraction. The others were the compost of home and public gardening residues and the compost of the mix of the above residues, digestate and sewage sludge. These materials were hydrolyzed under alkaline conditions to yield the biopolymers by saponification. The biopolymers were characterized by ¹³C NMR spectroscopy, elemental analysis and potentiometric titration. The titration data were elaborated to attain chemical models for interpretation of the proton-binding capacity of the biopolymers obtaining the acidic sites concentrations and their protonation constants. The results obtained with the models and by NMR spectroscopy were elaborated together in order to better characterize the nature of the macromolecules. The chemical nature of the biopolymers was found dependent upon the nature of the sourcing materials.     

Pectins from Aloe Vera: Extraction and production of gels for regenerative medicine

Extraction, purification, and gel preparation of Aloe Vera pectin and the evaluation of the biocompatibility of the pectin gels were studied, considering as end use as implantable materials for regenerative medicine. A. Vera was chosen as source of pectin, as this pectin was described to possess high molecular weight and a low degree of esterification. As the properties of pectins are strictly dependent upon the extraction methods in combination with the natural source, the extraction method was modified in order to optimize the yield of the final product, its purity, the duration of the process and the selection of non‐toxic chemical reagents. Changing the experimental conditions resulted in four different extraction processes and products with different physical and chemical characteristics. The optimal extraction resulted to be the process: with enzimatic deactivation by microwave and the use of sodium citrate as chelating agent the molecular weight of the pectin extracted was estimated to be 118 kDa and the 2.93% esterification degree. Cytocompatibility of pectin gels, prepared by ionotropic gelation, showing an improved cell adhesion if compared to commercial pectin. The results suggest that the extracted A. Vera pectins possess interesting properties to be exploited for the production of mechanically stable gels by ionotropic gelation and high rhamnose content matrices for application in regenerative medicine. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39760.     

Nutrient balance of shifting cultivation by burning or mulching in the Eastern Amazon – evidence for subsoil nutrient accumulation

For over a hundred years shifting cultivation with slash-and-burn land preparation has been the predominant type of land use by smallholders in the Bragantina region of the Brazilian Eastern Amazon. This study contrasts the nutrient balance of slash-and-burn agriculture with a fire-free cultivation. Therefore, one half of a 3.5-year-old (28.7 t DM ha^–1) and a 7-year-old woody fallow vegetation (46.5 t DM ha^–1) was burnt and the other half mulched, leaving the biomass as a surface residue. Subsequently, a sequence of maize, beans and cassava was cropped for 1.5 year. Burning the 3.5- and 7-year-old fallow removed 97 and 94% of the C, 98 and 96% of the N, 90 and 63% of the P-stocks, and between 45 and 70% of the cations K, Mg and Ca of the aboveground biomass by volatilization or ash-particle transfer. These losses were avoided with the slash-and-mulch land preparation. Mulching did not increase the losses of nutrients by leaching, despite the high amount of rapidly decomposing surface mulch. Also the length of preceding fallow had no significant influence on leaching losses. At a depth of 3 m, leached nutrients were quantitatively negligible in both treatments. Comparing the nutrient fluxes at soil depths of 0.9 m, 1.8 m and 3 m, the amounts of all mobile nutrients, and also of chloride and sodium were markedly reduced during percolation and must have been retained. It is likely that nutrient retention in the subsoil layer is only temporary, emphasizing the need for a rapid re-establishment of the naturally deep-rooting secondary vegetation after abandonment of sites to enable uptake of these nutrients. The overall nutrient balance was highly negative for slash-and-burn. 291 and 403 kg N ha^–1, 21 and 18 kg P ha^–1, and 70 and 132 kg K ha^–1 were removed from the burnt plots with a preceding fallow of 3.5 and 7 years, respectively. A reduced fallow period (3.5 years), which is a common trend in the region, resulted in a higher mean annual rate of nutrient loss averaged over the duration of the cycle than a fallow period of 7 years. Eliminating the burning losses by mulching brought the agricultural system back to an equilibrated or even slightly positive nutrient balance, even after a reduced fallow period. Thus, slash-and-mulch is a viable alternative to maintain agricultural productivity and ecosystem functioning.     

Effective molarities in supramolecular catalysis of two-substrate reactions

Reactivity data related to processes in which molecular receptors promote the reaction of two simultaneously complexed reactants have been surveyed and analyzed in terms of effective molarity (EM). Methods and criteria for the calculation of reliable EM's have been highlighted. Extension of a previous extrathermodynamic treatment of intramolecular reactions of bifunctional chains to the intracomplex reactions of the ternary complexes involved in two-substrate catalyzed reactions has provided a sound framework for a comparative analysis of reactivity and catalytic efficiency in structurally diverse and apparently unrelated systems.     

On the Role of Oxygen Storage in Three-Way Catalysis

The role of the so-called oxygen storage and release capacity (OSC) in promoting the activity of noble metals in the three-way catalysts (TWCs) is critically discussed. It is shown that the promoting effects of CeO₂ in the TWCs cannot be attributed to a simple redox type of effect according to the reaction CeO₂ ? CeO_{2 ? x} + x/2O₂, since multiple and sometimes intriguing effects of CeO₂ promoter have been observed, particularly in the latest generation of TWCs containing modified CeO₂–ZrO₂ mixed oxides.     

Geranylgeraniol and Neurological Impairment: Involvement of Apoptosis and Mitochondrial Morphology

Deregulation of the cholesterol pathway is an anomaly observed in human diseases, many of which have in common neurological involvement and unknown pathogenesis. In this study we have used Mevalonate Kinase Deficiency (MKD) as a disease-model in order to investigate the link between the deregulation of the mevalonate pathway and the consequent neurodegeneration. The blocking of the mevalonate pathway in a neuronal cell line (Daoy), using statins or mevalonate, induced an increase in the expression of the inflammasome gene (NLRP3) and programmed cell death related to mitochondrial dysfunction. The morphology of the mitochondria changed, clearly showing the damage induced by oxidative stress and the decreased membrane potential associated with the alterations of the mitochondrial function. The co-administration of geranylgeraniol (GGOH) reduced the inflammatory marker and the damage of the mitochondria, maintaining its shape and components. Our data allow us to speculate about the mechanism by which isoprenoids are able to rescue the inflammatory marker in neuronal cells, independently from the block of the mevalonate pathway, and about the fact that cell death is mitochondria-related.     

Clinical managers' identity at the crossroad of multiple institutional logics in it innovation: The case study of a health care organization in England

Clinical managers play a crucial role in securing the implementation and sustainability of information technology (IT) innovation in health care. Yet, not all clinical managers are willing and able to support IT innovation, particularly when the institutional logics of an IT innovation challenge their professional practice. We investigate how clinical managers use their hybrid identities to reconcile differences among competing institutional logics that affect IT innovation. Based on three examples of IT innovation (telehealth for obstructive sleep apnoea, telehealth for heart failure, and electrocardiograms) in a health care organization in England, we identify three roles in IT innovation (innovation advocate, innovation broker, and innovation laggard) that clinical managers enacted in response to three degrees of conflict between institutional logics (no conflict, moderate conflict, and high conflict), respectively. We make the following contributions. First, we demonstrate how clinical managers' perception of their hybrid role in relation to their professional identity influences their response to the conflicting institutional demands of IT innovation. We conclude that clinical managers' fragmented identities can compromise their ability to effectively manage IT innovation in health care. Second, our findings raise implications for understanding the role of professionals' hybrid identities in the implementation of digital transformation at the intersection of multiple institutional logics.