Accuracy of FIB-4 to Detect Elevated Liver Stiffness Measurements in Patients with Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study in Referral Centers

The identification of advanced fibrosis by applying noninvasive tests is still a key component of the diagnostic algorithm of NAFLD. The aim of this study is to assess the concordance between the FIB-4 and liver stiffness measurement (LSM) in patients referred to two liver centers for the ultrasound-based diagnosis of NAFLD. Fibrosis 4 Index for Liver Fibrosis (FIB-4) and LSM were assessed in 1338 patients. A total of 428 (32%) had an LSM ≥ 8 kPa, whereas 699 (52%) and 113 (9%) patients had an FIB-4 < 1.3 and >3.25, respectively. Among 699 patients with an FIB-4 < 1.3, 118 (17%) had an LSM ≥ 8 kPa (false-negative FIB-4). This proportion was higher in patients ≥60 years, with diabetes mellitus (DM), arterial hypertension or a body mass index (BMI) ≥ 27 kg/m². In multiple adjusted models, age ≥ 60 years (odds ratio (OR) = 1.96, 95% confidence interval (CI) 1.19–3.23)), DM (OR = 2.59, 95% CI 1.63–4.13), body mass index (BMI) ≥ 27 kg/m² (OR = 2.17, 95% CI 1.33–3.56) and gamma-glutamyltransferase ≥ 25 UI/L (OR = 2.68, 95% CI 1.49–4.84) were associated with false-negative FIB-4. The proportion of false-negative FIB-4 was 6% in patients with none or one of these risk factors and increased to 16, 31 and 46% among those with two, three and four concomitant risk factors, respectively. FIB-4 is suboptimal to identify patients to refer to liver centers, because about one-fifth may be false negative at FIB-4, having instead an LSM ≥ 8 KPa.     

Metabolic and DNA Repair Variations in Susceptibility to Genotoxins

An overview on the influence of metabolic and DNA repair polymorphisms on biological indicators of genotoxic risk in occupational, environmental, or lifestyle exposure is presented in this article. Indicators of genotoxic risk include biomarkers of internal dose (urinary concentration of the substance or its metabolites and urinary mutagenicity), biological effective dose (protein and DNA adducts), and indicators of early biological effects (chromosome aberrations, sister chromatid exchanges, micronuclei, COMET assay, HPRT mutants). Genetic polymorphisms include those involved in the activation and detoxification (i.e., P-450 cytochrome, acetyltransferase, glutathione transferase) of various classes of carcinogens and the newly discovered polymorphisms affecting DNA repair enzymes. Genetic polymorphisms are assessed for their importance in detecting the impact of genotype on biological indicators of genotoxic risk.     

Effect of mechanical and air-particle cleansing protocols of provisional cement on immediate dentin sealing layer and subsequent adhesion of resin composite cement

Immediate dentin sealing (IDS) could avoid contamination of dentin from impression material and provisional cement but prior to final cementation of indirect restorations, removal of the provisional cement may damage the IDS. The objectives of this study were to investigate the effect of mechanical and air-particle cleansing protocols of provisional cement on IDS layer and subsequent adhesion of resin composite cement. The cuspal dentin surfaces of human third molars (N = 21, n_quadrant = 84) were exposed by a low-speed diamond saw under water cooling and conditioned with an adhesive system based on the three-step etch and rinse technique (OptiBond FL). Provisional cement (Freegenol) was applied on each specimen. They were then randomly divided into six subgroups where the provisional cement was removed either by (1) air-borne particle abrasion with 50-μm Al₂O₃ particles at 2 bar (AL2), (2) air-borne particle abrasion with 50-μm Al₂O₃ particles at 3.5 bar (AL3.5), (3) air-borne particle abrasion with 30-μm SiO₂ particles at 2 bar (SL2), (4) air-borne particle abrasion with 30-μm SiO₂ particles at 3.5 bar (SL3.5), (5) prophylaxy paste (Cleanic) (PP) or (6) pumice-water slurry (PW) at 1500 rpm for 15 s. The dentin surface on each tooth was assigned to four quadrants and each quadrant received the cleansing methods in a clockwise sequence. The non-contaminated and non-cleansed teeth acted as the control (C). Two separate teeth, contaminated and cleansed according to six cleansing protocols, were allocated for scanning electron microscopy (SEM) analysis (×2000). The dentin surfaces in each quadrant received resin composite luting cement (Variolink II, Ivoclar Vivadent) incrementally in a polyethylene mould (diameter: 1 mm²; height: 4 mm) and photopolymerized. The specimens were stored in distilled water for 24 h at 37 °C until the testing procedures and then shear force was applied to the adhesive interface until failure occurred in a universal testing machine (0.5 mm/min). Microshear bond (μSBS) was calculated by dividing the maximum load (N) by the bonding surface area of the resin cement. Failure types were analysed using optical microscope and SEM. Data (MPa) were analysed using one-way ANOVA (α = 0.05). Two-parameter Weibull distribution values including the Weibull modulus, scale (m) and shape (₀), values were calculated. Mean μSBS results (MPa) showed a significant difference between the experimental groups (p = 0.011) and were in a descending order as follows: C (8 ± 2.3)^a < AL2 (6.7 ± 2.4)^b < PP (6.9 ± 2)^b < PW (6.5 ± 2.1)^b < AL3.5 (5.8 ± 1.1)^b < SL2 (5.3 ± 1)^b < SL3.5 (5.2 ± 1)^b. Failure types were predominantly mixed failure type between the dentin and the adhesive resin which is a combination of adhesive and cohesive failures in the adhesive resin. Cohesive failure in the dentin was not observed in any of the groups. Weibull distribution presented lower shape (₀) for C (3.9), AL2 (3.2), PP (3.5) and PW (3.6). SEM analysis showed rough surfaces especially in the air-abraded groups whereas mechanical cleansing methods presented smoother surfaces and partially covered by particle remnants all of which occluded the dentin tubuli.     

Regulation by Different Types of Chaperones of Amyloid Transformation of Proteins Involved in the Development of Neurodegenerative Diseases

The review highlights various aspects of the influence of chaperones on amyloid proteins associated with the development of neurodegenerative diseases and includes studies conducted in our laboratory. Different sections of the article are devoted to the role of chaperones in the pathological transformation of alpha-synuclein and the prion protein. Information about the interaction of the chaperonins GroE and TRiC as well as polymer-based artificial chaperones with amyloidogenic proteins is summarized. Particular attention is paid to the effect of blocking chaperones by misfolded and amyloidogenic proteins. It was noted that the accumulation of functionally inactive chaperones blocked by misfolded proteins might cause the formation of amyloid aggregates and prevent the disassembly of fibrillar structures. Moreover, the blocking of chaperones by various forms of amyloid proteins might lead to pathological changes in the vital activity of cells due to the impaired folding of newly synthesized proteins and their subsequent processing. The final section of the article discusses both the little data on the role of gut microbiota in the propagation of synucleinopathies and prion diseases and the possible involvement of the bacterial chaperone GroE in these processes.     

Structure Formation of Integral Asymmetric Composite Membranes of Polystyrene‐block‐Poly(2‐vinylpyridine) on a Nonwoven

The formation of an integral asymmetric membrane composed of a cylinder‐forming polystyrene‐block‐poly(2‐vinylpyridine) on a nonwoven by using solvent casting followed by solvent/nonsolvent exchange (phase inversion) is reported for the first time. The influence of parameters such as solvent composition, evaporation time of the solution‐cast block copolymer film before phase inversion, and immersion bath temperature is demonstrated. The optimized membranes are characterized in terms of stimuli‐responsive water flux properties. The morphologies of the membranes as well as of the bulk of the block copolymer are imaged by scanning force microscopy, scanning electron microscopy, and transmission electron microscopy.

     

Incorporation of polyfluorenes into poly(lactic acid) films for sensor and optoelectronics applications

Films of neat and plasticized biodegradable poly(lactic acid) (PLA) matrices containing anionic conjugated polyelectrolytes, poly[9,9‐bis(4‐phenoxybutylsulfonate)]fluorene‐2,7‐diyl‐alt‐arylenes, with 1,4‐phenylene and 4,4″‐p‐terphenylene, respectively, as arylene groups or a neutral poly(9,9‐dialkylfluorene) for comparison were prepared by solution casting. These films were characterized using differential scanning calorimetry, thermogravimetry, scanning electron microscopy and fluorescence spectroscopy. In addition, the effects of plasticizer on the thermal properties and the oxygen permeability of the PLA films were measured through the oxygen transmission rate. Results show that it is possible to obtain thin, optically transparent and luminescent films with potential in oxygen sensing, exhibiting good thermal and photochemical stability. At high polyelectrolyte content, evidence is found for phase separation and aggregate formation and it is no longer possible to obtain completely homogeneous films. The possibility of incorporating the cationic metal complex tris(2,2′‐bipyridyl)ruthenium(II) into plasticized PLA films containing conjugated polyelectrolytes for dual‐wavelength ratiometric luminescence sensing is also discussed. Copyright © 2012 Society of Chemical Industry     

Synthesis and Biological Studies of Pyrazolyl‐Diamine PtII Complexes Containing Polyaromatic DNA‐Binding Groups

New [PtCl(pz*NN)]ⁿ⁺ complexes anchored by pyrazolyl‐diamine (pz*NN) ligands incorporating anthracenyl or acridine orange DNA‐binding groups have been synthesized so as to obtain compounds that would display synergistic effects between platination and intercalation of DNA. Study of their interaction with supercoiled DNA indicated that the anthracenyl‐containing complex L²Pt displays a covalent type of binding, whereas the acridine orange counterpart L³Pt shows a combination of intercalative and covalent binding modes with a strong contribution from the former. L²Pt showed a very strong cytotoxic effect on ovarian carcinoma cell lines A2780 and A2780cisR, which are, respectively, sensitive to and resistant to cisplatin. In these cell lines, L²Pt is nine to 27 times more cytotoxic than cisplatin. In the sensitive cell line, L³Pt showed a cytotoxic activity similar to that of cisplatin, but like L²Pt was able significantly to overcome cisplatin cross‐resistance. Cell‐uptake studies showed that L²Pt accumulates preferentially in the cytoplasm, whereas L³Pt reaches the cell nucleus more easily, as clearly visualized by time‐lapse confocal imaging of live A2870 cells. Altogether, these findings seem to indicate that interaction with biological targets other than DNA might be involved in the mechanism of action of L²Pt because this compound, despite having a weaker ability to target the cell nucleus than L³Pt , as well as an inferior DNA affinity, is nevertheless more cytotoxic. Furthermore, ultrastructural studies of A2870 cells exposed to L²Pt and L³Pt revealed that these complexes induce different alterations in cell morphology, thus indicating the involvement of different modes of action in cell death.     

Spontaneous Oleofoams from Water-in-Oil Emulsions

Spontaneously foaming oil systems have been formulated from water-in-oil emulsions by the controlled release and entrapment of gas in emulsified water droplets contained within the oil. The cascade of events leading to their formation is as follows: Two Span 60-emulsified populations of water droplets, one containing Na₂CO₃, the other 10% HCl and caseinate, were mixed in miglyol oil; the controlled coalescence of Na₂CO₃ droplets with the HCl ones served as a microreactor for the pH reduction and the subsequent release of CO₂ from Na₂CO₃; these gas microbubbles were arrested by sodium caseinate, stabilizing a microfoam within the water droplets; these droplets expanded under the rising gas pressure, spontaneously transforming the surrounding oil into a foamy oleogel containing water droplets.     

Phenylvinilbisquinolines as fluorescent markers in functionalized polypropylene films

Polymer Bulletin - In this work, polypropylene films (PP) and maleic anhydride graft polypropylene (PPgMA) at different concentrations of a photoluminescent dye 2,2′-(1,4-phenylenedivinylene)...     

Iridium complexes incorporating coumarin moiety as catalyst photoinitiators: Towards household green LED bulb and halogen lamp irradiation

Household LED bulbs and halogen lamps are used to promote the ring-opening photopolymerization of epoxides in the presence of a new series of iridium(III) complexes (IrCs) exhibiting enhanced visible light absorption properties through the introduction of a coumarin moiety. These latter complexes are used as catalyst photoinitiators in an oxidative cycle in combination with a silane and an iodonium salt. Remarkably, even under the selected very soft irradiations (e.g. light intensity lower than 2 mW/cm²), excellent polymerization profiles are obtained (conversions > 80%). The mechanisms are investigated by ESR and luminescence experiments.