Head and neck cancer (HNC) exerts a significant healthcare burden worldwide. Insufficient data impedes a comprehensive understanding of its global impact. Through analysis of the 2019 Global Burden of Disease (GBD) database, our secondary investigation unveiled a surging global incidence of HNC, yet a decline in associated mortality and disability-adjusted life years (DALYs) owing to enhanced prognosis. Particularly noteworthy is the higher incidence of escalation among females compared to males. Effective resource allocation, meticulous control of risk factors, and tailored interventions are imperative to curtail mortality rates among young individuals afflicted with HNC in underprivileged regions, as well as in elderly individuals grappling with thyroid cancer.

Hidden hearing refers to the functional deficits in hearing without deterioration in hearing sensitivity. This concept is proposed based upon recent finding of massive noise-induced damage on ribbon synapse between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in the cochlea without significant permanent threshold shifts (PTS). Presumably, such damage may cause coding deficits in auditory nerve fibers (ANFs). However, such deficits had not been detailed except that a selective loss of ANFs with low spontaneous rate (SR) was reported. In the present study, we investigated the dynamic changes of ribbon synapses and the coding function of ANF single units in one month after a brief noise exposure that caused a massive damage of ribbon synapses but no PTS. The synapse count and functional response measures indicates a large portion of the disrupted synapses were re-connected. This is consistent with the fact that the change of SR distribution due to the initial loss of low SR units is recovered quickly. However, ANF coding deficits were developed later with the re-establishment of the synapses. The deficits were found in both intensity and temporal processing, revealing the nature of synaptopathy in hidden hearing loss.

Object: The authors evaluated the behavior of residual tumors and facial nerve outcomes after incomplete excision of vestibular schwannomas (VSs). Methods: The case records of all patients who underwent surgical treatment of VSs were analyzed. All patients in whom an incomplete excision had been performed were analyzed. Incomplete excision was defined as near-total resection (NTR), subtotal resection (STR), and partial resection (PR). Tumors in the NTR and STR categories were followed up with a wait-and-rescan approach, whereas the tumors in the PR category were subjected to a second-stage surgery and were excluded from this series. All patients included in the study underwent baseline MRI at the 3rd and 12th postoperative months, and repeat imaging was subsequently performed every year for 7–10 years postoperatively or as indicated clinically. Preoperative and postoperative facial function was noted. Results: Of the 2368 patients who underwent surgery for VS, 111 patients who had incomplete excisions of VSs were included in the study. Of these patients, 73 (65.77%) had undergone NTR and 38 (34.23%) had undergone STR. Of the VSs, 62 (55.86%) were cystic and 44 (70.97%) of these cystic VSs underwent NTR. The residual tumor was left behind on the facial nerve alone in 62 patients (55.86%), on the facial nerve and vessels in 2 patients (1.80%), on the facial nerve and brainstem in 15 patients (13.51%), and on the brainstem alone in 25 patients (22.52%). In the 105 patients with normal preoperative facial nerve function, postoperative facial nerve function was House-Brackmann (HB) Grades I and II in 51 patients (48.57%), HB Grade III in 34 patients (32.38%), and HB Grades IV–VI in 20 patients (19.05%). Seven patients (6.3%) showed evidence of tumor regrowth on follow-up MRI. All 7 patients (100%) who showed evidence of tumor regrowth had undergone STR. No patient in the NTR group exhibited regrowth. The Kaplan-Meier plot demonstrated a 5-year tumor regrowth-free survival of 92%, with a mean disease-free interval of 140 months (95% CI 127–151 months). The follow-up period ranged from 12 to 156 months (mean 45.4 months). Conclusions: The authors' report and review of the literature show that there is undoubtedly merit for NTR and STR for preservation of the facial nerve. On the basis of this they propose an algorithm for the management of incomplete VS excisions. Patients who undergo incomplete excisions must be subjected to follow-up MRI for a period of at least 7–10 years. When compared with STR, NTR via an enlarged translabyrinthine approach has shown to have a lower rate of regrowth of residual tumor, while having almost the same result in terms of facial nerve function.

The genetic correction of induced pluripotent stem cells (iPSCs) induced from somatic cells of patients with sensorineural hearing loss (caused by hereditary factors) is a promising method for its treatment. The correction of gene mutations in iPSCs could restore the normal function of cells and provide a rich source of cells for transplantation. In the present study, iPSCs were generated from a deaf patient with compound heterozygous MYO7A mutations (c.1184G>A and c.4118C>T; P-iPSCs), the asymptomatic father of the patient (MYO7A c.1184G>A mutation; CF-iPSCs), and a normal donor (MYO7AWT/WT; C-iPSCs). One of MYO7A mutation sites (c.4118C>T) in the P-iPSCs was corrected using CRISPR/Cas9. The corrected iPSCs (CP-iPSCs) retained cell pluripotency and normal karyotypes. Hair cell-like cells induced from CP-iPSCs showed restored organization of stereocilia-like protrusions; moreover, the electrophysiological function of these cells was similar to that of cells induced from C-iPSCs and CF-iPSCs. These results might facilitate the development of iPSC-based gene therapy for genetic disorders. Significance: Induced pluripotent stem cells (iPSCs) were generated from a deaf patient with compound heterozygous MYO7A mutations (c.1184G>A and c.4118C>T). One of the MYO7A mutation sites (c.4118C>T) in the iPSCs was corrected using CRISPR/Cas9. The genetic correction of MYO7A mutation resulted in morphologic and functional recovery of hair cell-like cells derived from iPSCs. These findings confirm the hypothesis that MYO7A plays an important role in the assembly of stereocilia into stereociliary bundles. Thus, the present study might provide further insight into the pathogenesis of sensorineural hearing loss and facilitate the development of therapeutic strategies against monogenic disease through the genetic repair of patient-specific iPSCs.

Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for development of dyslipidemia. Continuous positive airway pressure (CPAP) is the first-line treatment for OSAS. However, it is unclear whether CPAP improves lipid metabolism. To review the effect of CPAP on lipid profile of patients with OSAS. We searched PubMed, Embase, and the Cochrane Library to identify eligible articles published prior to October 30, 2013. Six randomized controlled trials (RCTs) were subjected to meta-analysis using Comprehensive Meta-Analysis software. Six RCTs meeting the inclusion criteria were enrolled. The total numbers of measurements of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol, in CPAP intervention patients and sham/control groups, were 370 and 371, 330 and 328, 276 and 274, and 269 and 266 respectively. The pooled estimate of the difference in the mean TC level between the CPAP and sham CPAP/control groups was significantly different (-0.15 [95% confidence interval, -0.27 to -0.03]; p = 0.01). Subgroup analysis revealed that OSAS patients of younger age, who were more obese, and who had been treated via CPAP for a longer duration, showed a significant decrease in TC levels (the differences in the means were -0.27, -0.24, and -0.20; and the p values 0.001, 0.01, and 0.04, respectively). We confirmed that CPAP decreases the TC level, especially in OSAS patients who are younger, more obese, and who use CPAP for a longer period. CPAP did not alter TG, LDL, or HDL levels, suggesting that CPAP may have no clinically important effect on lipid metabolism.

Glutamate is traditionally viewed as the first messenger to activate NMDAR (N-methyl-d-aspartate receptor)-dependent cell death pathways in stroke^1,2, but unsuccessful clinical trials with NMDAR antagonists implicate the engagement of other mechanisms^3–7. Here we show that glutamate and its structural analogues, including NMDAR antagonist l-AP5 (also known as APV), robustly potentiate currents mediated by acid-sensing ion channels (ASICs) associated with acidosis-induced neurotoxicity in stroke⁴. Glutamate increases the affinity of ASICs for protons and their open probability, aggravating ischaemic neurotoxicity in both in vitro and in vivo models. Site-directed mutagenesis, structure-based modelling and functional assays reveal a bona fide glutamate-binding cavity in the extracellular domain of ASIC1a. Computational drug screening identified a small molecule, LK-2, that binds to this cavity and abolishes glutamate-dependent potentiation of ASIC currents but spares NMDARs. LK-2 reduces the infarct volume and improves sensorimotor recovery in a mouse model of ischaemic stroke, reminiscent of that seen in mice with Asic1a knockout or knockout of other cation channels^4–7. We conclude that glutamate functions as a positive allosteric modulator for ASICs to exacerbate neurotoxicity, and preferential targeting of the glutamate-binding site on ASICs over that on NMDARs may be strategized for developing stroke therapeutics lacking the psychotic side effects of NMDAR antagonists.