Ca 2+ -binding protein 2 (CaBP2) inhibits the inactivation of heterologously expressed voltage-gated Ca 2+ channels of type 1.3 (Ca V 1.3) and is defective in human autosomal-recessive deafness 93 (DFNB93). Here, we report a newly identified mutation in CABP2 that causes a moderate hearing impairment likely via nonsense-mediated decay of CABP2-mRNA. To study the mechanism of hearing impairment resulting from CABP2 loss of function, we disrupted Cabp2 in mice (Cabp2 LacZ/LacZ ). CaBP2 was expressed by cochlear hair cells, preferentially in inner hair cells (IHCs), and was lacking from the postsynaptic spiral ganglion neurons (SGNs). Cabp2 LacZ/LacZ mice displayed intact cochlear amplification but impaired auditory brainstem responses. Patch-clamp recordings from Cabp2 LacZ/LacZ IHCs revealed enhanced Ca 2+ -channel inactivation. The voltage dependence of activation and the number of Ca 2+ channels appeared normal in Cabp2 LacZ/LacZ mice, as were ribbon synapse counts. Recordings from single SGNs showed reduced spontaneous and sound-evoked firing rates. We propose that CaBP2 inhibits Ca V 1.3 Ca 2+ -channel inactivation, and thus sustains the availability of Ca V 1.3 Ca 2+ channels for synaptic sound encoding. Therefore, we conclude that human deafness DFNB93 is an auditory synaptopathy.H earing relies on faithful transmission of information at ribbon synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs; recently reviewed in refs. 1, 2). Ca 2+ channels at the IHC presynaptic active zone are key signaling elements because they couple the sound-evoked IHC receptor potential to the release of glutamate. IHC Ca 2+ -channel complexes are known to contain Ca V 1.3 α1 subunit (Cav1.3α1) (3-5), betasubunit 2 (Ca V β2) (6), and alpha2-delta subunit 2 (α2δ2) (7) to activate at around −60 mV (8-10), and are partially activated already at the IHC resting potential in vivo [thought to be between −55 and −45 mV (11, 12)], thereby mediating "spontaneous" glutamate release during silence (13).Compared with Ca V 1.3 channels studied in heterologous expression systems, Ca V 1.3 channels in IHCs show little inactivation, which has been attributed to inhibition of calmodulin-mediated Ca 2+ -dependent inactivation (CDI) (14-17) by Ca 2+ -binding proteins (CaBPs) (18,19) and/or the interaction of the distal and proximal regulatory domains of the Ca V 1.3α1 C terminus (20)(21)(22). This "noninactivating" phenotype of IHC Ca V 1.3 enables reliable excitation-secretion coupling during ongoing stimulation (23-25). In fact, postsynaptic spike rate adaptation during ongoing sound stimulation is thought to reflect primarily presynaptic vesicle pool depletion, with minor contributions of Ca V 1.3 inactivation or AMPA-receptor desensitization (23-26). CaBPs are calmodulin-like proteins that use three functional out of four helix-loop-helix domains (EF-hand) for Ca 2+ binding (27). They are thought to function primarily as signaling proteins (28) and differentially modulate calmodulin effectors (29,30). In addition, CaBPs m...

The patients' mean age was 58.7 years; the mean hospital stay was 2.97 days. In 42 cases (87.5%), cauterization of the sphenopalatine artery was performed, and 6 (12.5%) were subjected to anterior ethmoid artery treatment. Epistaxis control was achieved in 93% of cases; 3 patients had a recurrent nasal bleeding, and were treated with anterior nasal packing. Minor complications occurred in 27.1%. We achieved a shorter hospital stay compared with patients who underwent anteroposterior packing.

Sinonasal inverted papilloma (IP) is the most common benign epithelial tumor in the nasal cavity and paranasal sinuses, with a worldwide incidence between 0.6 and 1.5/100 000 persons per year. However, only a few studies have investigated patient-dependent factors related to IP recurrence and persistence. According to available evidence, these factors are still debated, and results are contradictory. In this multicenter retrospective study, we analyzed the clinical records of 130 patients who were surgically treated for sinonasal IP to evaluate the factors affecting recurrence and persistence of IP and compared the curative rates of different surgical approaches. Our analysis showed that IP recurrence is strongly related to specific risk factors including incomplete surgical removal, stage of disease, site of the lesion, surgical technique, and malignancy rate. In conclusion, the recurrence of IP may be affected by several risk factors; these factors must be carefully considered during clinical evaluation and especially during the follow-up of patients with IP.

The here reported toxicity data are promising and encouraging in regard to the adoption of moderate hypofractionation with VMAT-SIB techniques, when cetuximab is concomitantly administered.

Background: Several authors highlighted the limitations of the Keros classification system in predicting intracranial entry risk. Recently, our group proposed a new classification system based on the angle formed between the lateral lamella of the cribriform plate (LLCP) and the continuation of an horizontal plane passing through the cribriform plate (Gera classification). The aim of this study was to analyze whether the risk of iatrogenic cerebrospinal fluid leak (CSF-L) was better predicted by Keros or Gera classification. Methodology: The pre-operative CT scans of 24 patients (CSF-L group) who suffered from iatrogenic CSF-L during endoscopic sinus surgery (ESS) were compared to those obtained from a group of 100 patients who underwent uneventful ESS (control group). The skull base measurements as well as the distribution of Keros and Gera classes in the 2 groups were analyzed. Results: No difference in the distribution of Keros classes or in the depth of the cribriform plate between CSF-L and control group were demonstrated. On the contrary, significant differences in the distribution of Gera classes and in the degree of the angle formed by the LLCP and the continuation of the horizontal plane passing through the cribriform plate were found. In particular, according to Gera classification system, 19 out of 24 patients in the CSF-L group were considered at risk for iatrogenic CSF-L. Conclusions: Gera classification system might be more sensitive to anatomical variations associated with CSF-L than the Keros' one, further suggesting the application of the former during the preoperative CT scan evaluation.