Assessment of EtQxBox complexation in solution by steady-state and time-resolved fluorescence spectroscopy

Reliable chemical sensors with high selectivity and sensitivity toward specific target molecules require rational synthesis of receptors, in-depth characterization of their complexation abilities and highly efficient transduction of the molecular recognition event. Here we report a steady-state and time-resolved fluorescence investigation of EtQxBox, a fluorescent conformationally blocked quinoxaline-based cavitand, aimed at assessing its selectivity toward aromatic versus non-aromatic analytes in solution. Fluorescence quenching of the EtQxBox in acetone is observed at increasing concentration of both aromatic (i.e. benzonitrile) and aliphatic (i.e. acetonitrile) compounds. The combination with fluorescence lifetime measurements permits to discriminate the predominantly static quenching of the aromatic analyte, due to non-fluorescent host–guest complex formation, from the mostly dynamic quenching of the non-aromatic compound, resulting from aspecific diffusive collisions between the fluorophore and the quencher. The equilibrium association constants for both the complexes have been estimated using Stern–Volmer model.

We investigate the role of combined static and dynamic quenching in fluorescence transduction of benzonitrile and acetonitrile complexation by a rigid quinoxaline-based cavitand.     

Factors affecting long-term changes of liver stiffness in direct-acting anti-hepatitis C virus therapy: A multicentre prospective study

The long-term changes of liver stiffness (LS) in patients who achieve viral clearance after direct-acting anti-HCV therapy remain undefined. We conducted a multicentre prospective study to investigate this aspect. Patients with HCV infection treated with DAAs were enrolled from six Italian centres; they underwent clinical, biochemical, ultrasound and transient elastography evaluations before treatment (T0), 12 weeks (SVR12) and 24 months (T24) after the end of therapy. Among the 516 consecutive patients enrolled, 301 had cirrhosis. LS significantly decreased from T0 to SVR (14.3 vs 11.1 kPa, p = .002), with a progressive reduction until T24 (8.7 kPa, p < .001). However, only patients with steatosis and those who developed HCC did not experience a late improvement in LS. Multivariate analysis of baseline and follow-up variables identified steatosis as the only independent predictor of failure of LS improvement (OR 1.802, p = .013). ROC curve analysis of the association of LS with the risk of developing HCC showed that SVR12 ≥14.0 kPa had the highest accuracy (sensitivity 82%, specificity 99%; AUC: 0.774). Multivariate analysis revealed that LS was the only variable independently associated with an increased risk of developing HCC (OR 6.470, p = .035). Achieving an SVR was associated with a progressive, long-term decline of LS, suggesting a late improvement in liver fibrosis, besides the resolution of inflammation. Fatty liver and the development of HCC interfered with late reduction of LS. Patients with an LS ≥14 kPa at 12 weeks after the end of treatment were at higher risk for developing HCC.     

Atrial fibrillation ablation: is common practice far from guidelines’ world? The Italian experience from a national survey

Journal of Interventional Cardiac Electrophysiology - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, occurring in 1–2% of the general population. Catheter ablation...     

Recombinant human thyrotropin reduces serum vascular endothelial growth factor levels in patients monitored for thyroid carcinoma even in the absence of thyroid tissue

In this study, we have investigated in vivo the time-dependent effects of TSH on vascular endothelial growth factor (VEGF) production in patients monitored for thyroid carcinoma. Serum VEGF, thyroglobulin (Tg), and TSH levels were assayed at baseline and 6, 24, 30, 48, 72, and 96 h and 1 wk after administration of recombinant human TSH (rhTSH) in 45 thyroidectomized patients affected by differentiated thyroid carcinoma. At baseline, the patients with metastasis (18 cases) showed serum Tg and VEGF values significantly higher than those seen in the cured patients (27 cases). During rhTSH stimulation, the mean VEGF levels decreased significantly in both patient groups. In 60% of patients with metastasis, VEGF nadir occurred at the same time as serum TSH reached the highest values, whereas in 85.7% of the cured patients VEGF decreased after the TSH peak (P = 0.003). In conclusion, we demonstrate for the first time that short-term administration of rhTSH in patients monitored for differentiated thyroid carcinoma induces a significant reduction in serum VEGF values even in the absence of thyroid tissue. This result would suggest that TSH may be able in vivo to regulate VEGF production from tissues other than the thyroid gland.