Genetic determinants in a critical domain of ns5a correlate with hepatocellular carcinoma in cirrhotic patients infected with hcv genotype 1b

HCV is an important cause of hepatocellular carcinoma (HCC). HCV NS5A domain‐1 interacts with cellular proteins inducing pro‐oncogenic pathways. Thus, we explore genetic variations in NS5A domain‐1 and their association with HCC, by analyzing 188 NS5A sequences from HCV genotype‐1b infected DAA‐naïve cirrhotic patients: 34 with HCC and 154 without HCC. Specific NS5A mutations significantly correlate with HCC: S3T (8.8% vs. 1.3%, p = 0.01), T122M (8.8% vs. 0.0%, p < 0.001), M133I (20.6% vs. 3.9%, p < 0.001), and Q181E (11.8% vs. 0.6%, p < 0.001). By multivariable analysis, the presence of >1 of them independently correlates with HCC (OR (95%CI): 21.8 (5.7–82.3); p < 0.001). Focusing on HCC‐group, the presence of these mutations correlates with higher viremia (median (IQR): 5.7 (5.4–6.2) log IU/mL vs. 5.3 (4.4–5.6) log IU/mL, p = 0.02) and lower ALT (35 (30–71) vs. 83 (48–108) U/L, p = 0.004), suggesting a role in enhancing viral fitness without affecting necroinflammation. Notably, these mutations reside in NS5A regions known to interact with cellular proteins crucial for cell‐cycle regulation (p53, p85‐PIK3, and β‐ catenin), and introduce additional phosphorylation sites, a phenomenon known to ameliorate NS5A interaction with cellular proteins. Overall, these results provide a focus for further investigations on molecular bases of HCV‐mediated oncogenesis. The role of these NS5A domain‐1 mutations in triggering pro‐oncogenic stimuli that can persist also despite achievement of sustained virological response deserves further investigation

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Synthesis and photophysical properties of poly(arylene ethynylene) small-molecules and polymers derivatized with leucine substituents

Aminoacidic/peptidic functionalized poly(aryleneethynylenes) (PAEs) are bio-inspired smart hybrids of great potential as active components in sensing devices. These materials synergically combine the superb photophysical properties of highly ethynylated unsaturated backbones with the large possibility of aminoacid and peptide design towards specific target-analyte binding. Conformational changes and/or electron density variations occurring along the PAE conjugated path, as a consequence of analyte binding to the aminoacidic/peptidic receptor site, might dramatically change the optoelectronic properties of the material, thus signaling the presence of the analyte. In this paper, we have studied the photochemistry of two groups of L-leucine/polyarylene-etynylene small molecules and polymers with the aim of optimizing the photochemical performances of aminoacidic derivatized PAE structures, in view of their use for metal sensing. Taking into account that among the different chemical sensors, fluorescence-based ones present many advantages in terms of sensitivity, selectivity, no need of references, and multiple readout signals, we have searched for more insight into the evolution of the optical properties of oligomers and polymers as a function of the structure of the PAE aminoacidic assembling

Glucose homeostasis in acromegaly: pathogenesis and effects of treatment

Acromegaly is a chronic debilitating disorder resulting from excessive secretion of growth hormone (GH) and consequent increase in insulin-like growth factor I (IGF-I), usually caused by a pituitary somatotroph adenoma. Effective treatment aims to ameliorate symptoms and signs of the disease and to lower mortality rate. In particular, high morbidity and mortality are partly related to the presence of insulin resistance due to the action of GH on liver, muscle and adipose tissue. Insulin resistance and/or reduced insulin sensitivity physiologically result in hypersecretion of insulin from the pancreas. This compensatory state of hyperinsulinemia is felt to be a first and more important marker for this condition. Adequate control of GH excess by surgery or pharmacotherapy is associated with decreased insulin resistance, resulting in reduced plasma insulin and glucose levels or improved glucose tolerance. Despite divergent effects of both somatostatin and somatostatin analogs on GH, insulin and glucagon secretion, and glucose absorption, treatment with the somatostatin analogs octreotide and lanreotide has only limited effects on glucose metabolism. However, glucose sensitivity has been formally examined using a hyperinsulinemic euglycemic clamp only in a minority of studies. Treatment with the GH-receptor antagonist pegvisomant improves insulin sensitivity, thus decreasing circulating fasting insulin and glucose levels. Assessment of insulin secretion and glucose levels in acromegalic patients during administration of the above compounds is thus mandatory

Chemical-physical characterisation of 5-Phenyl-1H-tetrazole inhibitive behaviour: a new non-toxic compound for a sustainable protection of Cu-alloys

The inhibitive effect against copper-alloy corrosion in NaCl 3 wt% of a non-toxic compound, namely 5-Phenyl-1H-tetrazole (PT), is probed and compared with the performance of the most used and toxic 1H-Benzotriazole (BTA), by using a multi-technique approach. Electrochemical impedance spectroscopy and potentiodynamic polarisation measurements, at different inhibitors concentrations, are performed in order to evaluate the best inhibition efficiency (IE%) and the optimum concentration of the inhibitors. The inhibition efficiencies of PT (IE = 94.7-96.1%) and BTA (IE = 99.5-99.9%) are comparable, with the advantage that PT acts at a much lower concentration (1 mM respect to 10 mM). To shed light on the inhibition mechanism at the early stage of the corrosion (2 h), we investigate the samples surfaces composition and morphology by X-ray photoelectron spectroscopy, micro-Raman spectroscopy and atomic force microscopy. Different inhibition mechanism and patina composition are observed and commented for the two inhibitors. The reported experimental tests suggest PT as a promising candidate for replacing toxic BTA in the prevention of bronze archaeological and artistic objects corrosion.[GRAPHICS]

Appropriateness of clinical criteria for the use of symptomatic slow-acting drug for osteoarthritis (SYSADOA). A Delphi method consensus initiative among experts in Italy

OsteoArthritis (OA) is a theme currently representing an emerging topic for its increasing incidence. It is well known that it is a chronic disease that could lead to important long-lasting disability; this generates increasing costs for the health care system. OA treatment options vary: localization, aetiology, grading and symptomatology should be considered before choosing the most adequate therapy. Currently, a modern approach to managing OA involves SYmptomatic Slow Acting Drugs in Osteo-Arthritis (SYSADOAs). However, while all preparations may claim to deliver a therapeutic level of glucosamine or chondroitin, not all of them are supported by clinical evidence. Recently the European Society for Clinical and Economic aspects of Osteoporosis, Osteoarthritis and musculoskeletal diseases (ESCEO), produced an evidenced based document providing practitioners with the latest clinical and economic informations, thereby allowing them to optimize the management of knee OA. According to this report, only crystalline glucosamine sulphate and the pharmaceutical-grade chondroitin sulphate are considered as effective in the first line approach to treating knee OA as an alternative drug to acetaminophen. However, some OA guidelines do not agree are not concordant in recommending the use of SYSADOA, perhaps because they are generally considered as a class and distinctions among formulations aren't made