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Background: Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene result in defective Cl - transport and cause chronic bacterial infections in the upper and lower airways of cystic fibrosis (CF) patients. Ivacaftor is a CFTR potentiator that improves Cl - transport in CF patients with at least 1 copy of the G551D mutation. Resveratrol is also a potent CFTR potentiator that increases determinants of mucociliary transport. The objective of this study is to determine whether resveratrol and ivacaftor improve Cl - secretion in G551D CFTR over either agent alone., Methods: Fisher rat thyroid cells (FRT) transfected with G551D CFTR and human sinonasal epithelial cells (HSNE) containing the CFTR G551D mutation were subjected to pharmacologic manipulation of transepithelial ion transport in Ussing chambers. Activity was further evaluated using whole-cell patch clamp methods in G551D FRT cells., Results: In G551D FRT cells, resveratrol (100 μM) and ivacaftor (10 μM) significantly increased Cl - transport (change in short-circuit current, δI SC = μA/cm 2 ) compared with single-agent and dimethylsulfoxide vehicle controls (resveratrol + ivacaftor 4.97 ± 0.57 vs ivacaftor 0.74 ± 0.12 vs resveratrol 2.96 ± 0.52 vs control 0.74 ± 0.12; p < 0.001). Maximal Cl - secretion (20 μM forskolin) was also significantly enhanced (p < 0.0001). Activity was confirmed in G551D HSNE (resveratrol + ivacaftor 4.48 ± 0.39 vs ivacaftor 1.05 ± 0.11 vs. resveratrol 0.84 ± 0.3 vs control, 0.0 ± 0.02; p < 0.001), and whole-cell patch clamp analysis in G551D FRT cells (resveratrol + ivacaftor -2535 ± 179.3 pA vs ivacaftor -1408.9 ± 101.3 pA vs resveratrol; -766.2 ± 71.2 pA; p < 0.0001)., Conclusion: Additive improvement in G551D CFTR-mediated Cl - secretion suggests that resveratrol could enhance ivacaftor therapy in these patients and improve CF-related rhinosinusitis., (© 2018 ARS-AAOA, LLC.)

Background: Biofilms may contribute to refractory chronic rhinosinusitis (CRS), as they lead to antibiotic resistance and failure of effective clinical treatment. l-Methionine is an amino acid with reported biofilm-inhibiting properties. Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator with mild antimicrobial activity via inhibition of bacterial DNA gyrase and topoisomerase IV. The objective of this study was to evaluate whether co-treatment with ivacaftor and l-methionine can reduce the formation of Pseudomonas aeruginosa biofilms., Methods: P aeruginosa (PAO-1 strain) biofilms were studied in the presence of l-methionine and/or ivacaftor. For static biofilm assays, PAO-1 was cultured in a 48-well plate for 72 hours with stepwise combinations of these agents. Relative biofilm inhibitions were measured according to optical density of crystal violet stain at 590 nm. Live/dead assays (BacTiter-Glo™ assay, Promega) were imaged with laser scanning confocal microscopy. An agar diffusion test was used to confirm antibacterial effects of the drugs., Results: l-Methionine (0.5 μM) significantly reduced PAO-1 biofilm mass (32.4 ± 18.0%; n = 4; p < 0.001) compared with controls. Low doses of ivacaftor alone (4, 8, and 12 μg/mL) had no effect on biofilm formation. When combined with ivacaftor (4 μg/mL), a synergistic anti-biofilm effect was noted at 0.05 μM and 0.5 μM of l-methionine (two-way analysis of variane, p = 0.0415) compared with corresponding concentrations of l-methionine alone., Conclusion: Ivacaftor enhanced the anti-biofilm activity of l-methionine against the PAO-1 strain of P aeruginosa. Further studies evaluating the efficacy of ivacaftor/l-methionine combinations for P aeruginosa sinusitis are planned., (© 2018 ARS-AAOA, LLC.)

Surnames were obtained for the second half of the 20th century from civil and religious marriage registers on fifteen Provençal-Italian and five Italian villages of Cuneo Province, Italy. To insert in the analysis an outward comparison, surnames from two Italian villages of Turin Province, one parish of Turin, one village of Alessandria Province and one village of Asti Province were also collected. Ethnicity does not seem to be the main factor affecting the present genetic structure of the Provençal-Italians. They are an open community, and evidence the end of the genetic isolation of the alpine populations.

Surnames of grandparents were collected from children in the primary schools of the Albanian-Italian, Croat-Italian and Greek-Italian villages of southern Italy and Sicily. The coefficients of relationships by isonymy show almost no relationship with ethnicity. Ethnolinguistic minorities of southern Italy and Sicily are geographically subdivided into two main clusters: the first cluster comprises the Albanian, Croat and Greek communities of the Adriatic area; and the second cluster comprises the Albanian and Greek communities of the Ionian, Thirrenian and Sicilian areas.