Prognostic factors in non-organic hearing loss in children.

OBJECTIVE: Exploring factors that predict a favourable clinical outcome in non-organic hearing loss (NOHL) in children. NOHL is defined as a subjective hearing loss without correlation in objective measures. DESIGN: Retrospective analysis of all childrens' data with the diagnosis NOHL seen between 2005 and 2017 at a tertiary referral centre. STUDY SAMPLE: Sixty-seven children (44 female, 23 male; mean age 11.26 years) were included. Statistical analyses included descriptive statistics, logistic regression, correlations, and Mann-Whitney U tests. RESULTS: A quarter of the children (17/67) had been provided previously with hearing aids without objective sensorineural hearing loss. Having been provided with hearing aids before the first visit to our clinic lowered the chance of normal hearing at the final visit by 76%. The prescription of hearing aids was significantly more likely in girls. Children provided with hearing aids were significantly older than those without and the time span between the first occurrence of the NOHL and first presentation at our department was longer than in children not provided with hearing aids. CONCLUSIONS: In cases of NOHL, hearing aid prescription is not indicated and significantly lowers a child's chance of full recovery and, thus, should not be prescribed unless NOHL is ruled out.

Embryonic lethal abnormal vision-like HuR-dependent mRNA stability regulates post-transcriptional expression of cyclin-dependent kinase inhibitor p27Kip1.

The cyclin-dependent kinase inhibitor p27(Kip1) plays a critical role in regulating entry into and exit from the cell cycle. Post-transcriptional regulation of p27(Kip1) expression is of significant interest. The embryonic lethal abnormal vision (ELAV)-like RNA-binding protein HuR is thought be important for the translation of p27(Kip1), however, different reports attributed diametrically opposite roles to HuR. We report here an alternative mechanism wherein HuR regulates stability of the p27(Kip1) mRNA. Specifically, human and mouse p27(Kip1) mRNAs interact with HuR protein through multiple U-rich elements in both 5' and 3' untranslated regions (UTR). These interactions, which occur in vitro and in vivo, stabilize p27(Kip1) mRNA and play a critical role in its accumulation. Deleting HuR binding sites or knocking down HuR expression destabilizes p27(Kip1) mRNA and reduces its accumulation. We also identified a CT repeat in the 5' UTR of full-length p27(Kip1) mRNA isoforms that interact with a approximately 41-kDa protein and represses p27(Kip1) expression. This CT-rich element and diffuse elements in the 3' UTR regulate post-transcriptional expression of p27(Kip1) at the level of translation. This is the first demonstration that HuR-dependent mRNA stability and HuR-independent mRNA translation plays a critical role in the regulation of post-transcriptional p27(Kip1) expression.