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.     

Sol–Gel Processing and Characterization of Pure and Metal-Doped SnO2 Thin Films

A chloride-based inorganic sol–gel route was used for preparing pure and metal (osmium, nickel, palladium, platinum)-doped SnO₂ sol. SnCl₄ was first reacted with propanol, then the resulting compound was hydrolyzed and subsequently mixed with solutions of the metal dopants. The obtained sols were used for depositing thin films by spin coating or for preparing powders by solvent evaporation at 110°C. FTIR spectroscopy and thermal analysis of the powders revealed that chlorine still bound to tin stabilized the sol against gelation by hindering the condensation reactions. Film characterizations showed that platinum and palladium, unlike nickel and osmium, were likely to form nanoparticles in the SnO₂ lattice. This result was discussed with regard to the different ways that platinum and palladium, on one hand, and nickel and osmium, on the other, modified the growth of SnO₂ grains and the film roughness and morphology. Dopants that formed nanoparticles (platinum, palladium) resulted in the roughest film, while dopants that did not form particles (nickel, osmium) resulted in SnO₂ grain size very close to that of pure SnO₂.     

The Emerging Role of Epigenetics in Therapeutic Targeting of Cardiomyopathies

Cardiomyopathies (CMPs) are a heterogeneous group of myocardial diseases accountable for the majority of cases of heart failure (HF) and/or sudden cardiac death (SCD) worldwide. With the recent advances in genomics, the original classification of CMPs on the basis of morphological and functional criteria (dilated (DCM), hypertrophic (HCM), restrictive (RCM), and arrhythmogenic ventricular cardiomyopathy (AVC)) was further refined into genetic (inherited or familial) and acquired (non-inherited or secondary) forms. Despite substantial progress in the identification of novel CMP-associated genetic variations, as well as improved clinical recognition diagnoses, the functional consequences of these mutations and the exact details of the signaling pathways leading to hypertrophy, dilation, and/or contractile impairment remain elusive. To date, global research has mainly focused on the genetic factors underlying CMP pathogenesis. However, growing evidence shows that alterations in molecular mediators associated with the diagnosis of CMPs are not always correlated with genetic mutations, suggesting that additional mechanisms, such as epigenetics, may play a role in the onset or progression of CMPs. This review summarizes published findings of inherited CMPs with a specific focus on the potential role of epigenetic mechanisms in regulating these cardiac disorders.     

Novel Procedure for Lager Beer Clarification and Stabilization Using Sequential Enzymatic,Centrifugal, Regenerable PVPP and Crossflow Microfiltration Processing

In this work, the crossflow microfiltration (CFMF) performance of different lots of lager beer, produced in a pilot scale at the Italian Brewing Research Centre (CERB, Perugia, Italy), was assessed in a bench-top plant, equipped with a 0.8-μm ceramic tubular membrane module, under constant crossflow velocity of 6 m s^?1, transmembrane pressure difference of 3.74 bar, temperature of ~10 °C, and periodic CO₂ backflushing. By feeding different beer samples (i.e., as such, precentrifuged (C), or pretreated with a commercial enzyme preparation to degrade the original arabinoxylans and β-glucans and then centrifuged (EC) to minimize the fouling contribution of yeast cells, aggregates, and polysaccharides), it was possible to increase the average permeation flux (expressed as mean value?±?standard deviation) from 112?±?13 to 199?±?17 or 330?±?22 L m^?2 h^?1, respectively. Only when using the EC-pretreated beer specimens, the permeate turbidity at 20 °C approached the limiting one (<0.6 EBC unit) recommended by the European Brewery Convention standards. As expected, the permeate chill haze at 0 °C was generally higher than the above haze target. By submitting EC-pretreated beer seeded with 0.5 g L^?1 of regenerable polyvinylpolypyrrolidone (PVPP) to CFMF, it was possible to reduce the initial total polyphenol content by 30 % and permeate chill haze to 0.60?±?0.01 EBC unit, but the average permeation flux fell to 84?±?4 L m^?2 h^?1. By performing sequentially EC pretreatments, PVPP stabilization, cartridge filtration, and CFMF, it was possible not only to re-enhance the average permeation flux at about 230 L m^?2 h^?1 near to those achievable with DE filters, but also to obtain a chill haze-free permeate ready for aseptic packaging.     

Sensor-containing microspheres of chitosan crosslinked with 8-hydroxyquinoline-5-sulphonic acid for determination of Cu(II) in instant coffee

A novel carbon paste electrode containing chitosan microspheres for the determination of Cu(II) in instant coffee by anodic stripping voltammetry was developed. Chitosan was crosslinked with the chelating agent 8-hydroxyquinoline-5-sulphonic acid and glutaraldehyde. The microspheres of the crosslinked chitosan biopolymer were obtained by the spray drying technique and employed in the construction of the sensor. In acetate buffer solution (0.1 mol L⁻¹, pH 6.0), the calibration curve obtained was linear for concentrations of 5.0 × 10⁻⁷ to 1.4 × 10⁻⁵ mol L⁻¹ (r = 0.9990); the detection limit was 5.5 × 10⁻⁸ mol L⁻¹. The relative standard deviation (n = 8) was lower than 3.0% for solutions containing 6.0 × 10⁻⁶, 5.0 × 10⁻⁵ and 1.5 × 10⁻⁴ mol L⁻¹ of Cu(II). The method was successfully employed for determination of Cu(II) in instant coffee and the results obtained showed good agreement when compared with those using electrothermal atomic absorption spectrometry.     

Anthocyanin composition and extractability in berry skin and wine of Vitis vinifera L. cv. Aglianico

BACKGROUND: The present article reports the anthocyanin content in the berry skin and wine of the Italian red grape cultivar Aglianico (clone VCR11 grafted onto 1103 Paulsen), one of the most ancient vines and famous for its deep‐red colour. Anthocyanins were extracted from frozen berry skin in an acidified methanol solution. The extraction mixtures, monitored for 120 h, were analysed by high‐performance liquid chromatography. RESULTS: The extraction from berry skin of delphinidin, petunidin and malvidin appeared to be a time‐independent process, whereas the concentration of peonidin increased linearly with time. Peonidin‐O‐acetyl‐glucoside was transferred from skin more slowly than petunidin‐O‐acetyl‐glucoside and malvidin‐O‐acetyl‐glucoside. The anthocyanin composition of the resulting wine showed that the total anthocyanin content was about one‐tenth of the corresponding berry skin content. The ratio acetyl/coumaroyl anthocyanins in the wine was sharply higher than the value in berry skin (0.85 and 0.10, respectively), indicating an enrichment of acetyl derivatives in the wine. CONCLUSION: Levels of single anthocyanins in wine were not always correlated with those detected in grapes, as they were affected by winemaking. The high values of some anthocyanins in Aglianico wine could ameliorate its quality, increasing the chromatic properties, aging stability and product acceptance. Copyright © 2011 Society of Chemical Industry     

Monitoring of perfluorinated compounds in edible fish from the Mediterranean Sea

Perfluorooctanoic acid (PFOA) and perfluorooctane sulphonate (PFOS) are environmental contaminants belonging to a chemical group known as perfluorinated compounds (PCFs). The United States Environmental Protection Agency (US EPA) considers both compounds to be carcinogenic. The goal of the present study was to evaluate the contamination levels of PFOS and PFOA in edible fish of the Mediterranean Sea. Twenty six fish muscles, 17 fish livers, five series of cephalopods (each composed of ten specimens) and thirteen series of bivalves (each composed of about 50 specimens) were used for the investigation. A fast sample treatment, followed by an LC–ESI–MS/MS method is described for the identification, and quantification of PFOA and PFOS in fish. The method was in-house-validated through the determination of precision, accuracy, specificity, calibration curve, decision limit (CCα), and detection capability (CCβ). The results showed PFOA and PFOS levels in fishes and molluscs lower than those reported for analogue matrices in different geographic areas. Therefore, our biomonitoring results did not show that the Mediterranean Sea had any particularly alarming pollution by PFCs, although it is located in a semi-closed basin with scarce water change. Nonetheless, a worrying element is that a few fish showed extremely high contamination by PFOA and PFOS. This finding needs further clarification in order to assess whether such unusual contamination is linked to “dot-like” pollutant release, which could explain the anomaly.     

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.     

Unique Crystal Structure of a Novel Surfactant Protein from the Foam Nest of the Frog Leptodactylus vastus

Breeding by releasing eggs into stable biofoams (“foam nests”) is a peculiar reproduction mode within anurans, fish, and tunicates; not much is known regarding the biochemistry or molecular mechanisms involved. Lv‐ranaspumin (Lv‐RSN‐1) is the predominant protein from the foam nest of the frog Leptodactylus vastus. This protein shows natural surfactant activity, which is assumed to be crucial for stabilizing foam nests. We elucidated the amino acid sequence of Lv‐RSN‐1 by de novo sequencing with mass‐spectrometry and determined the high‐resolution X‐ray structure of the protein. It has a unique fold mainly composed of a bundle of 11 α‐helices and two small antiparallel β‐strands. Lv‐RSN‐1 has a surface rich in hydrophilic residues and a lipophilic cavity in the region of the antiparallel β‐sheet. It possesses intrinsic surface‐active properties, reducing the surface tension of water from 73 to 61 mN m^?1 (15 μg mL^?1). Lv‐RSN‐1 belongs to a new class of surfactants proteins for which little has been reported regarding structure or function.