OBJECTIVE: To investigate the changes of electrode impedance, THR/MCL values, and dynamic range (DR) in Combi 40+ cochlear implant after implantation. METHOD: A respective study was carried out collecting 20 consecutively implanted children's electrode impedances, THR/MCL values, and DR at seven time point during the first three years after implantation. Their variation and correlations were analyzed. RESULT: Overall, electrode impedances were lowest during the operation, and significantly rise to the highest at the first stimulation, then followed by a gradual decrease. After three months, electrode impedance of apical and medial cochlear segment were basically stable, while that of the basal segment was gradually increased. Dynamic range (DR) of apical and medial group electrode increased early after the operation and showed a stabilization from the second year, whereas that of basal group have a downward trend since the first year. However, the electric charge of each group increased significantly after three months, and then become stable after first year. Otherwise, a stronger negative rectilinear correlation was found between impedance changes with DR than with THR/MCL level. CONCLUSION The electrode impedances vary clue to different electrode position. Measuring the electrode impedance can effectively evaluate the working status of Combi C40+ cochlear implant. The dynamic range of the electrode was negatively correlated with the impedances, which made it possible to predict the width of the dynamic range by measuring the impedance 3 or 6 months after operation.
Auditory Threshold ; Child ; Child, Preschool ; Cochlear Implantation ; Cochlear Implants ; Electric Impedance ; Electrodes ; Female ; Hearing Loss ; physiopathology ; rehabilitation ; Humans ; Male

OBJECTIVETo study the effect of Mps1 on BRAFWT/MEK/ERK pathway in the presence of wild type BRAF or BRAFV600E in melanoma.

METHODSMelanoma cells harboring BRAFWT genotype were transfected either with pBabe-puro-GST-BRAF-WT and/or pBabe-puro-GFP-Mps1-WT or pBabe-puro-GST-BRAFV600E and/or pBabe-puro-GFP-Mps1-WT, followed by Western blot to detect Mps1 and p-ERK expression. The melanoma cells harboring BRAFWT and BRAFV600E genotype were infected with pSUPER-Mps1 retrovirus to knockdown the endogenous Mps1 protein, followed by Western blot to detect Mps1 and p-ERK expression. Meanwhile, melanoma cells harboring BRAFV600E genotype were infected with pBabe-puro-GFP-Mps1 and Western blot was performed to detect Mps1 and p-ERK expression.

RESULTSIn melanoma cells harboring BRAFWT genotype and transfected with pBabe-puro-GST-BRAF-WT and pBabe-puro-GFP-Mps1-WT, phospho-ERK levels were notably reduced as compared to either negative control or empty vector. However, cells transfected with pBabe-puro-GST-BRAFV600E and pBabe-puro-GFP-Mps1-WT, phospho-ERK levels did not change significantly compared with either negative control or empty vector. Knockout of Mps1 in BRAF wild-type cell lines led to an increased ERK activity. However, there was no significant change of ERK activity in BRAFV600E cell lines in the absence of Mps1. The expression of p-ERK in BRAFV600E mutant cell lines infected with pBabe-puro-GFP-Mps1-WT did not show any significant difference from either negative control or empty vector.

CONCLUSIONSBased on these findings, it suggests that there exists an auto-regulatory negative feedback loop between the Mps1 kinase and BRAFWT/ERK signaling. Oncogenic BRAFV600E abrogates the regulatory negative feedback loop of Mps1 on the MAPK pathway.

Cell Cycle Proteins ; metabolism ; Cell Line, Tumor ; Humans ; MAP Kinase Signaling System ; Melanoma ; genetics ; metabolism ; Mutation ; Phenotype ; Protein-Serine-Threonine Kinases ; metabolism ; Protein-Tyrosine Kinases ; metabolism ; Proto-Oncogene Proteins B-raf ; metabolism ; Signal Transduction ; Transfection