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Melanoma, the most lethal form of skin cancer, is frequently associated with alterations in several genes, among which the Bcl-2 oncogene plays an important role in progression, chemosensitivity and angiogenesis. Also microRNA (miRNA) are emerging as modulators of melanoma development and progression, and among them, miR-211, located within the melastatin-1/TRPM1 (transient receptor potential cation channel, subfamily M, member 1 protein) gene, is prevalently expressed in the melanocyte lineage and acts as oncosuppressor. Using several human melanoma cell lines and their Bcl-2 stably overexpressing derivatives, we evaluated whether there was a correlation between expression of Bcl-2 and miR-211. Western blot analysis and quantitative real-time polymerase chain reaction demonstrated reduced expression of pri-miR-211, miR-211, TRPM1, and MLANA levels, after Bcl-2 overexpression, associated with increased expression of well-known miR-211 target genes. Overexpression of mature miR-211 in Bcl-2 overexpressing cells rescued Bcl-2 ability to increase cell migration. A decreased nuclear localization of microphthalmia-associated transcription factor (MITF), a co-regulator of both miR-211 and TRPM1, and a reduced MITF recruitment at the TRPM1 and MLANA promoters were also evidenced in Bcl-2 overexpressing cells by immunofluorescence and chromatin immunoprecipitation experiments, respectively. Reduction of Bcl-2 expression by small interference RNA confirmed the ability of Bcl-2 to modulate miR-211 and TRPM1 expression. © 2015 Wiley Periodicals, Inc.

Background: A correlation between elevation of pro-inflammatory cytokines and white matter injury or abnormal neurologic outcome has been established in the preterm infant. In the full-term neonate, few studies exist linking elevation of cytokines with encephalopathy and poor neurodevelopmental outcome. Our aims were to investigate if serum interleukin-6 concentrations in delivering mothers and their offspring at birth are associated with perinatal asphyxia, and to examine the relation of interleukin-6 levels to the severity of hypoxic-ischemic encephalopathy and to the neurological outcome. Design and methods: Serum interleukin-6 levels were measured at birth, 24 and 48 h of life in 50 consecutive term uninfected newborns with perinatal asphyxia and 113 randomly selected healthy term newborns, and at delivery in their mothers. Results: The median cord interleukin-6 concentrations in the infants who developed hypoxic-ischemic encephalopathy was 376-fold as high as the values in the normal infants (P < 0.0001) and 5.5-fold as high as those in the infants with asphyxia who did not develop hypoxic-ischemic encephalopathy (P < 0.05). There was also a significant relationship between interleukin-6 and the degree of hypoxic-ischemic encephalopathy, and between interleukin-6 and neurodevelopmental outcome at 2 years of age. Regardless of outcome, in the asphyxiated infants the interleukin-6 values were significantly lower at both 24 and 48 h of life than at birth, with a significant decline from 24 to 48 h of life. Among mothers of the asphyxiated neonates, there were no significant differences in interleukin-6 concentrations between those delivering neonates with and without hypoxic-ischemic encephalopathy. Conclusions: Measurement of IL-6 concentrations in the umbilical cord of neonates with perinatal asphyxia may be useful to identify early, and in a relatively simple way, those who are most likely to have subsequent brain injury and adverse outcome.

Objective: Hemodynamic and clinical performances of 21-mm and 23-mm St Jude Medical Hemodynamic Plus aortic valves (St Jude Medical, Inc, St Paul, Minn) were compared with those of 21-mm and 23-mm St Jude Medical standard cuff aortic valves in the first such multicenter, prospective, randomized study. Hemodynamic Plus valves are mechanical, bileaflet prostheses suitable for the small aortic anulus. Methods: Patients with 21-mm and 23-mm anulus diameters were randomized to receive either a Hemodynamic Plus or a standard cuff valve. Postoperatively and at 6 months after the operation, patients underwent 2-dimensional Doppler echocardiography. Ejection fraction, cardiac output, peak gradient, mean gradient, effective orifice area, effective area index, and performance index were calculated. Postoperative and 6-month echocardiographic measurements and their variations across observation times were analyzed statistically. Results: Of the 140 patients enrolled, 5 died at operation and 1 died of aortic dissection during the follow-up period. Eight patients were lost to follow-up. A total of 125 patients completed the study. In 1 patient a sewing cuff escaped intraoperatively. At 6 months the 21-mm and 23-mm Hemodynamic Plus valves showed significantly lower peak gradients and mean gradients than those of the 21-mm and 23-mm standard cuff valves. The 21-mm Hemodynamic Plus valves had gradients similar to those of the 23-mm Hemodynamic Plus valves. The effective orifice area did not differ significantly between the Hemodynamic Plus and standard cuff valves at either measurement. No valve mismatch was found in the 4 groups of patients. A more enhanced decrease of peak gradients and mean gradients and a more enhanced increase of effective orifice areas, effective area indices, and performance indices were found across observation times for patients with Hemodynamic Plus valves compared with those with standard cuff valves. Conclusions: Clinical hemodynamic performances of 21-mm and 23-mm St Jude Medical Hemodynamic Plus valves correspond closely with those of standard cuff valves, and gradients are substantially better than those of standard cuff valves of the same diameter. Therefore, use of this valve may minimize the need for aortic anulus enlargement. Early follow-up results with the Hemodynamic Plus valves were excellent, although more time is required to confirm this outcome.

International audience; In this paper we introduce a general line search scheme which easily allows us to define and analyze known and new semismooth algorithms for the solution of nonlinear complementarity problems. We enucleate the basic assumptions that a search direction to be used in the general scheme has to enjoy in order to guarantee global convergence, local superlinear/quadratic convergence or finite convergence. We examine in detail several different semismooth algorithms and compare their theoretical features and their practical behavior on a set of large-scale problems.