Selenium-GPX4 axis protects follicular helper T cells from ferroptosis.

Follicular helper T (TFH) cells are a specialized subset of CD4+ T cells that essentially support germinal center responses where high-affinity and long-lived humoral immunity is generated. The regulation of TFH cell survival remains unclear. Here we report that TFH cells show intensified lipid peroxidation and altered mitochondrial morphology, resembling the features of ferroptosis, a form of programmed cell death that is driven by iron-dependent accumulation of lipid peroxidation. Glutathione peroxidase 4 (GPX4) is the major lipid peroxidation scavenger and is necessary for TFH cell survival. The deletion of GPX4 in T cells selectively abrogated TFH cells and germinal center responses in immunized mice. Selenium supplementation enhanced GPX4 expression in T cells, increased TFH cell numbers and promoted antibody responses in immunized mice and young adults after influenza vaccination. Our findings reveal the central role of the selenium-GPX4-ferroptosis axis in regulating TFH homeostasis, which can be targeted to enhance TFH cell function in infection and following vaccination.

Glutamate acts on acid-sensing ion channels to worsen ischaemic brain injury.

Glutamate is traditionally viewed as the first messenger to activate NMDAR (N-methyl-D-aspartate receptor)-dependent cell death pathways in stroke1,2, but unsuccessful clinical trials with NMDAR antagonists implicate the engagement of other mechanisms3-7. 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 channels4-7. 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.

Long-term haplodeficency of DSPP causes temporomandibular joint osteoarthritis in mice.

BACKGROUND: Extracellular matrix (ECM) protein malfunction or defect may lead to temporomandibular joint osteoarthritis (TMJ OA). Dentin sialophophoprotein (DSPP) is a mandibular condylar cartilage ECM protein, and its deletion impacted cell proliferation and other extracellular matrix alterations of postnatal condylar cartilage. However, it remains unclear if long-term loss of function of DSPP leads to TMJ OA. The study aimed to test the hypothesis that long-term haploinsufficiency of DSPP causes TMJ OA. MATERIALS AND METHODS: To determine whether Dspp+/- mice exhibit TMJ OA but no severe tooth defects, mandibles of wild-type (WT), Dspp+/-, and Dspp homozygous (Dspp-/-) mice were analyzed by Micro-computed tomography (micro-CT). To characterize the progression and possible mechanisms of osteoarthritic degeneration over time in Dspp+/- mice over time, condyles of Dspp+/- and WT mice were analyzed radiologically, histologically, and immunohistochemically. RESULTS: Micro-CT and histomorphometric analyses revealed that Dspp+/- and Dspp-/- mice had significantly lower subchondral bone mass, bone volume fraction, bone mineral density, and trabecular thickness compared to WT mice at 12 months. Interestingly, in contrast to Dspp-/- mice which exhibited tooth loss, Dspp+/- mice had minor tooth defects. RNA sequencing data showed that haplodeficency of DSPP affects the biological process of ossification and osteoclast differentiation. Additionally, histological analysis showed that Dspp+/- mice had condylar cartilage fissures, reduced cartilage thickness, decreased articular cell numbers and severe subchondral bone cavities, and with signs that were exaggerated with age. Radiographic data showed an increase in subchondral osteoporosis up to 18 months and osteophyte formation at 21 months. Moreover, Dspp+/- mice showed increased distribution of osteoclasts in the subchondral bone and increased expression of MMP2, IL-6, FN-1, and TLR4 in the mandibular condylar cartilage. CONCLUSIONS: Dspp+/- mice exhibit TMJ OA in a time-dependent manner, with lesions in the mandibular condyle attributed to hypomineralization of subchondral bone and breakdown of the mandibular condylar cartilage, accompanied by upregulation of inflammatory markers.

TMEM30A is essential for hair cell polarity maintenance in postnatal mouse cochlea.

BACKGROUND: Phosphatidylserine is translocated to the inner leaflet of the phospholipid bilayer membrane by the flippase function of type IV P-tape ATPase (P4-ATPase), which is critical to maintain cellular stability and homeostasis. Transmembrane protein 30A (TMEM30A) is the ß-subunit of P4-ATPase. Loss of P4-ATPase function causes sensorineural hearing loss and visual dysfunction in human. However, the function of TMEM30A in the auditory system is unclear. METHODS: P4-ATPase subtype expression in the cochlea was detected by immunofluorescence staining and quantitative real-time polymerase chain reaction (qRT-PCR) at different developmental stages. Hair cell specific TMEM30A knockout mice and wild-type littermates were used for the following functional and morphological analysis. Auditory function was evaluated by auditory brainstem response. We investigated hair cell and stereocilia morphological changes by immunofluorescence staining. Scanning electron microscopy was applied to observe the stereocilia ultrastructure. Differentially expressed transcriptomes were analyzed based on RNA-sequencing data from knockout and wild-type mouse cochleae. Differentially expressed genes were verified by qRT-PCR. RESULTS: TMEM30A and subtypes of P4-ATPase are expressed in the mouse cochlea in a temporal-dependent pattern. Deletion of TMEM30A in hair cells impaired hearing onset due to progressive hair cell loss. The disrupted kinocilia placement and irregular distribution of spectrin-α in cuticular plate indicated the hair cell planar polarity disruption in TMEM30A deletion hair cells. Hair cell degeneration begins at P7 and finishes around P14. Transcriptional analysis indicates that the focal adhesion pathway and stereocilium tip-related genes changed dramatically. Without the TMEM30A chaperone, excessive ATP8A2 accumulated in the cytoplasm, leading to overwhelming endoplasmic reticulum stress, which eventually contributed to hair cell death. CONCLUSIONS: Deletion of TMEM30A led to disrupted planar polarity and stereocilia bundles, and finally led to hair cell loss and auditory dysfunction. TMEM30A is essential for hair cell polarity maintenance and membrane homeostasis. Our study highlights a pivotal role of TMEM30A in the postnatal development of hair cells and reveals the possible mechanisms underlying P4-ATPase-related genetic hearing loss.

Microglial TLR4-induced TAK1 phosphorylation and NLRP3 activation mediates neuroinflammation and contributes to chronic morphine-induced antinociceptive tolerance.

BACKGROUND AND PURPOSE: The aim of this work was to investigate the role and signal transduction of toll-like receptor 4 (TLR4), TGF-ß-activated kinase 1 (TAK1) and nod-like receptor protein 3 (NLRP3) in microglial in the development of morphine-induced antinociceptive tolerance. METHODS: TLR4 and NLRP3 knockout mice and 5Z-7-oxozeaeno (a selective inhibitor against TAK1 activity) were used to observe their effect on the development of morphine tolerance. Intrathecal injections of morphine (0.75 mg/kg once daily for 7 days) were used to establish anti-nociceptive tolerance, which was measured by the tail-flick test. Spinal TLR4, TAK1, and NLRP3 expression levels and phosphorylation of TAK1 were evaluated by Western blotting and immunofluorescence. RESULTS: Repeated treatment with morphine increased total expression of spinal TLR4, TAK1, and NLRP3 and phosphorylation of TAK1 in wild-type mice. TLR4 knockout attenuated morphine-induced tolerance and inhibited the chronic morphine-induced increase in NLRP3 and phosphorylation of TAK1. Compared with controls, mice that received 5Z-7-oxozeaenol showed decreased development of morphine tolerance and inhibition on repeated morphine-induced increase of NLRP3 but not TLR4. NLRP3 knockout mice showed resistance to morphine-induced analgesic tolerance with no effect on chronic morphine-induced expression of TLR4 and TAK1. TLR4, TAK1, and NLRP3 were collectively co-localized together and with the microglia marker Iba1. CONCLUSIONS: Microglial TLR4 regulates TAK1 expression and phosphorylation and results in NLRP3 activation contributes to the development of morphine tolerance through regulating neuroinflammation. Targeting TLR4-TAK1-NLRP3 signaling to regulate neuro-inflammation will be alternative therapeutics and strategies for chronic morphine-induced antinociceptive tolerance.

Erythropoietin Plays a Protective Role in Submandibular Gland Hypofunction Induced by Irradiation.

PURPOSE: This study aims to explore the radioprotective effects of recombinant human erythropoietin (rhEPO) on rats' submandibular gland hypofunction induced by irradiation (IR). MATERIALS AND METHODS: Thirty rats were divided into 3 groups: 1) control group, 2) IR group, and 3) IR + rhEPO group. The IR group and IR + rhEPO group received a single dose of 15 Grays (Gy) (0.98 Gy/min), plus, the IR + rhEPO group also received subcutaneous administration of rhEPO at a dose of 3,000 IU/kg body weight 3 days before irradiation and then repeated every 24 hours for the first 2 weeks after irradiation. Immunohistochemistry analysis to erythropoietin receptor was performed to detect the levels of erythropoietin receptor in submandibular glands with or without radiation. Ninety days after irradiation, the salivary flow rates were assessed, and the submandibular gland of every rat was subjected to hematoxylin and eosin staining and immunohistochemical staining with antiaquaporin 5 and anti-proliferating cell nuclear antigen antibodies. Apoptosis was examined by the terminal deoxynucleotidyl transferase biotin-dUDP nick end-labeling assay. In addition, to examine the protective role of rhEPO on human submandibular gland cells, the apoptotic and proliferation rate of cells under a radiation dose of 8 Gy was detected. One-way analysis of variance was carried out to analyze the results of each group, and the P value was set at 0.05. RESULTS: Erythropoietin receptor was expressed in the submandibular glands at a low level under normal conditions but upregulated after irradiation. rhEPO administration remarkably alleviated gland atrophy, increased salivary flow rates with upregulation of aquaporin-5 compared with the IR group. In addition, fewer apoptotic cells and more proliferative cells were observed in the IR + rhEPO group compared with the IR group, both in vivo and in vitro. CONCLUSIONS: rhEPO administration may be a useful countermeasure to mitigate submandibular gland hypofunction after therapeutic radiation exposure.

Ultrasound-guided anterior iliopsoas muscle space block versus posterior lumbar plexus block in hip surgery in the elderly: A randomised controlled trial.

BACKGROUND: Ultrasound-guided posterior lumbar plexus block is widely used for hip fracture surgery but it requires a change of position, which may be painful. OBJECTIVES: Our primary objective was to describe a new technique, the anterior iliopsoas muscle space block, which can be performed in the supine position, and to test the hypothesis that its analgesia for hip surgery was similar to that of the traditional posterior lumbar plexus block. DESIGN: Randomised, double-blind study. SETTING: Shanghai 6th People's Hospital, China, from February to August 2019. PATIENTS: Forty-eight patients scheduled for unilateral hip fracture surgery were included in the study. The exclusion criteria were infection at the puncture site, history of hip surgery, pre-existing neurological deficits of the lower extremity, contraindications for regional anaesthesia, allergy to local anaesthetics, coagulopathy, abuse of medicine or alcohol, or daily consumption of analgesics. INTERVENTIONS: Patients were randomised to receive a lateral sacral plexus block with either an anterior iliopsoas muscle space block or a posterior lumbar plexus block, using 0.33% ropivacaine (30 ml each). MAIN OUTCOME MEASURES: The main outcome was verbal numerical scale (VNS) pain intensity 1 h after surgery in the postanesthesia care unit, and the secondary outcome was the dose of intra-operative fentanyl. The differences in VNS scores and fentanyl use between the groups were analysed. RESULTS: Based on previous work, we considered a difference (confidence interval [CI]) of 1.6 on the VNS to be significant. The median [IQR] pain scores in postanesthesia care unit were similar in the anterior 0 [0 to 3] and posterior groups 1.5 [0 to 3]. The median scores for intra-operative fentanyl use were similar in the anterior 20 [10 to 42.5] µg and posterior groups 15 [0 to 50] µg (P = 0.34). The difference in the median pain score at-rest was NS: anterior group 0.5 [0 to 5], posterior group 0 [0 to 2], median difference -0.5 (95% CI -2 to 0). The median post to preblock difference in VNS was higher in the anterior -0.5 [-2 to 0] than in the posterior group 0 [-1.25 to 0], median difference 0.5 (95% CI 0 to 1). The median block onset time was longer in the anterior 11 [6 to 14.25] min than in the posterior group 6 [4.75 to 8] min (P = 0.002), median difference -5 (95% CI -7 to -1). CONCLUSION: The anterior iliopsoas muscle space block had the same effect as the posterior lumbar plexus block on peri-operative analgesia for hip surgery, but with a longer onset time. Therefore, anterior iliopsoas muscle space block can be recommended as a routine technique for hip and lower limb procedures. TRIAL REGISTRATION: http://www.chictr.org.cn identifier: ChiCTR1900021214.

Can auditory brain stem response accurately reflect the cochlear function?

Auditory brain stem response (ABR) and compound action potential (CAP) recordings have been used in animal research to determine hearing sensitivity. Because of the relative ease of testing, the ABR test has been more commonly used in assessing cochlear lesions than the CAP test. The purpose of this experiment is to examine the difference between these two methods in monitoring the dynamic changes in auditory function after cochlear damage and in detecting asymmetric hearing loss due to unilateral cochlear damage. ABR and CAP were measured in two models of cochlear damage: acoustic trauma induced by exposure to a narrowband noise centered at 4 kHz (2,800-5,600 Hz) at 105 dB sound pressure level for 5 h in chinchillas and unilateral cochlear damage induced by surgical destruction of one cochlea in guinea pigs. Cochlear hair cells were quantified after completing the evoked potential testing. In the noise-damaged model, we found different recovery patterns between ABR and CAP. At 1 day after noise exposure, the ABR and CAP assessment revealed a similar level of threshold shifts. However, at 30 days after noise exposure, ABR thresholds displayed an average of 20-dB recovery, whereas CAP thresholds showed no recovery. Notably, the CAP threshold signifies the actual condition of sensory cell pathogenesis in the cochlea because sensory cell death is known to be irreversible in mammals. After unilateral cochlear damage, we found that both CAP and ABR were affected by cross-hearing when testing the damaged ear with the testing stimuli delivered directly into the canal of the damaged ear. When cross-hearing occurred, ABR testing was not able to reveal the presence of cross-hearing because the ABR waveform generated by cross-stimulation was indistinguishable from that generated by the test ear (damaged ear), should the test ear be intact. However, CAP testing can provide a warning sign, since the typical CAP waveform became an ABR-like waveform when cross-hearing occurred. Our study demonstrates two advantages of the CAP test over the ABR test in assessing cochlear lesions: contributing evidence for the occurrence of cross-hearing when subjects have asymmetric hearing loss and providing a better assessment of the progression of cochlear pathogenesis.NEW & NOTEWORTHY Auditory brain stem response (ABR) is more commonly used to evaluate cochlear lesions than cochlear compound action potential (CAP). In a noise-induced cochlear damage model, we found that the reduced CAP and enhanced ABR caused the threshold difference. In a unilateral cochlear destruction model, a shadow curve of the ABR from the contralateral healthy ear masked the hearing loss in the destroyed ear.

Contrast-Enhanced MRI Combined With the Glycerol Test Reveals the Heterogeneous Dynamics of Endolymphatic Hydrops in Patients With Menière's Disease.

BACKGROUND: The sensitivity of endolymphatic hydrops (EH) to the glycerol test varies in patients with Menière's disease (MD). PURPOSE: To explore the features of EH and its glycerol-induced dynamics in MD. STUDY TYPE: Case-control study. POPULATION: Twenty patients with MD (24 affected ears) were included. FIELD STRENGTH/SEQUENCE: 3.0T 3D-FLAIR (fluid-attenuated inversion recovery) MRI and late gadolinium enhancement. ASSESSMENT: Intratympanic gadolinium-enhanced MRI was performed in the MD-affected ears before and after the glycerol test. The borders of the endolymphatic and total lymphatic space were contoured on the axial MRI slices to evaluate the volume of hydrops in both the cochlear and vestibular regions. STATISTICAL TESTS: Paired and unpaired t-tests, the Mann-Whitney U-test, linear discriminant analysis, Pearson's correlation, and linear regression. RESULTS: After glycerol ingestion, vestibular EH decreased in all patients, whereas cochlear EH significantly decreased only in patients with positive glycerol test results (all P < 0.01). At baseline, cochlear EH in the positive result group was greater than in the negative result group (P = 0.007). Unexpectedly, in the positive result group a drastic glycerol-induced dehydrating effect was observed in patients whose pretest cochlear EH ratio was >16% (P = 0.011). Moreover, the dehydrating role of glycerol was positively correlated with the baseline cochlear hydrops level (r = 0.7691, P < 0.001). DATA CONCLUSION: MRI provides evidence that glycerol administration improves the hearing threshold via dehydrating the EH. In the cochlear region, the baseline level of cochlear EH is a closely related factor for the validity of the glycerol test, whereas EH is consistently dehydrated in the vestibular component. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3 J. Magn. Reson. Imaging 2020;52:1066-1073.

Investigation of the differences between the medical personnel's and general population's view on the doctor-patient relationship in China by a cross-sectional survey.

BACKGROUND: Due to economic development and an increase in the aging population, the demand for medical resources is increasing. A good doctor-patient relationship (DPR) can optimize patients' medical experience and improve treatment efficiency. The DPR, however, is currently in crisis in China. To explore ways to improve DPR, this study assessed the views on the status of the DPR, medical services, and the general situation of medical work among medical personnel (MP) and the general population (GP). METHODS: This cross-sectional study, conducted between December 2019 and March 2020, targeted the MP and the GP in Nanjing City, Jiangsu Province, and Zhengzhou City, Henan Province. A total of 154 MP and 329 GP answered a self-administered questionnaire through Questionnaire Star and WeChat apps. Wilcoxon's Sign Rank Test, Chi-square test, and frequency distributions and percentages were used to process the data. RESULTS: Only 11.04% of the MP and 14.89% of the GP believed that the current DPR was harmonious. Moreover, 54.55% of the MP and 71.12% of the GP believed that the medical industry was a service industry. While 14.29% of the MP and 64.44% of the GP thought medical staff earned high salaries, 19.48% of the MP and 47.11% of the GP wanted their children to be in the medical industry. The recognition of the current status of the DPR did not affect the GP's preference for their children's practice (p < 0.05). Most MPs hoped to improve salaries (40.26%), followed by safety (17.53%) and social status (12.99%); only 8.44% of the MP wanted to improve the DPR. CONCLUSION: The MP's and GP's views on the current status of DPR, the importance of medical service attitudes, and the general sense of the medical industry were similar. However, there was a significant difference in the perception of the nature of medical services and the income of the people employed in the medical industry between the two groups. Balancing the expectations of patients in the medical industry and increasing public awareness of the actual situation in the medical industry may be a feasible way to improve the DPR.

Effects of SoundBite Bone Conduction Hearing Aids on Speech Recognition and Quality of Life in Patients with Single-Sided Deafness.

Objectives: To analyze the clinical application of SoundBite bone conduction hearing aids by assessing the improvement of speech recognition and the scores of the benefit scale questionnaire for patients with single-sided deafness (SSD). Design: Nine patients aged 24 to 61 years with SSD for more than 3 months were enrolled in this study. The patients could understand and repeat Mandarin and have good compliance with the study. The measurements were evaluated before and after one month of wearing hearing aids using the pure tone audiometry threshold, speech recognition in quiet and in noise, and the Glasgow Benefit Inventory (GBI) benefit scale score. Results: Pure tone audiometry results showed that the average hearing threshold of good ears and bad ears was 11.4 ± 2.6 dB HL and 89.9 ± 6.4 dB HL, respectively. The average hearing threshold of bad ears after wearing hearing aids was 23.5 ± 9.0 dB HL. Statistical analysis showed that the hearing improvement for the bad ears after wearing hearing aids was significant. The speech audiometry results showed that the disyllable word recognition score of the bad ears in quiet increased significantly at 50 dB SPL by 40 ± 12 percentage points and at 65 dB SPL by 71 ± 15 percentage points. As for the speech recognition in noise, when the signal sound came from the bad ear side and the noise from the good ear side (SSSDNAH), the speech recognition score (SRS) significantly increased by 17 ± 6 and 9 ± 4 at a signal-to-noise ratio (SNR) of -2 dB and -5 dB, respectively, after wearing the hearing aids. When the signal sound came from the front of the patient and the noise from the bad ear side (S0NSSD), the SRS scores were reduced by 5 ± 5 and 7 ± 5 percentage points at SNR equal to -2 dB and -5 dB, which was significantly different from that before wearing the hearing aids. When the signal and noise both came from the front of the patients (S0N0), the SRS was not significantly increased by 5 ± 4 percentage points at SNR equal to -2 dB compared to before wearing hearing aids. However, the SRS was significantly increased by 5 ± 2 percentage points at SNR equal to -5 dB compared to before wearing hearing aids. The average total GBI score was 31 ± 12 for the nine patients, with an average score of 32 ± 10, 31 ± 8, and 30 ± 7 for general conditions, social support, and physical health, respectively. The results of the questionnaires showed that patients' quality of life was improved after wearing SoundBite bone conduction hearing aids. Conclusions: SoundBite bone conduction hearing aids are a good choice for patients with SSD, as it could improve the speech recognition ability of patients both in a quiet and noisy environment and improves the quality of life after wearing hearing aids.

Differences in Clinical Characteristics and Brain Activity between Patients with Low- and High-Frequency Tinnitus.

This study was aimed at delineating and comparing differences in clinical characteristics and brain activity between patients with low- and high-frequency tinnitus (LFT and HFT, respectively) using high-density electroencephalography (EEG). This study enrolled 3217 patients with subjective tinnitus who were divided into LFT (frequency < 4000 Hz) and HFT (≥4000 Hz) groups. Data regarding medical history, Tinnitus Handicap Inventory, tinnitus matching, and hearing threshold were collected from all patients. Twenty tinnitus patients and 20 volunteers were subjected to 256-channel EEG, and neurophysiological differences were evaluated using standardized low-resolution brain electromagnetic tomography (sLORETA) source-localized EEG recordings. Significant differences in sex (p < 0.001), age (p = 0.022), laterality (p < 0.001), intensity (p < 0.001), tinnitus type (p < 0.001), persistent tinnitus (p = 0.04), average threshold (p < 0.001), and hearing loss (p = 0.028) were observed between LFT and HFT groups. The tinnitus pitch only appeared to be correlated with the threshold of the worst hearing loss in the HFT group. Compared with the controls, the LFT group exhibited increased gamma power (p < 0.05), predominantly in the posterior cingulate cortex (PCC, BA31), whereas the HFT group had significantly decreased alpha1 power (p < 0.05) in the angular gyrus (BA39) and auditory association cortex (BA22). Higher gamma linear connectivity between right BA39 and right BA41 was observed in the HFT group relative to controls (t = 3.637, p = 0.027). Significant changes associated with increased gamma in the LFT group and decreased alpha1 in the HFT group indicate that tinnitus pitch is crucial for matching between the tinnitus and control groups. Differences of band frequency energy in brain activity levels may contribute to the clinical characteristics and internal tinnitus "spectrum" differences.

Anxiety and depression in patients with nasal septal deviation.

OBJECTIVE: Nasal septal deviation (NSD) has a significant impact on patients' quality of life; however, there have been limited studies examining the psychological status of NSD patients. In this study, symptoms of depression and anxiety were investigated between NSD patients and controls using a self-report questionnaire. METHODS: A case-control study design was used to evaluate the psychological burden of NSD in patients who visited the general hospital. The control group comprised of ENT outpatients without a history of chronic nasal disease. The Zung Self-rating Anxiety/Depression Scale (SDS/SAS) was used to evaluate the prevalence and severity of anxiety and depression between the NSD and control group. RESULTS: Seventy-six patients with NSD and 79 control patients were enrolled in the study. We found that depression and anxiety, as well as the co-morbidity of depression with anxiety, were more common in the NSD group in comparison to the control (39.5% vs 22.8%, p = 0.025; 38.2% vs 15.2%, p = 0.001; and 27.6% vs 11.4%, p = 0.011, respectively). The average SDS and SAS score was higher in NSD patients compared to controls (SDS: 49.7 ± 13.1 vs 45.2 ± 10.4, p = 0.019 and SAS: 48.1 ± 11.6 vs 41.3 ± 9.3, p < 0.001, respectively), and NSD patients were found to have more severe levels of anxiety and depression. CONCLUSION: Depression and anxiety are more common and severe in patients with NSD. Therefore, psychological distress should be taken into consideration during the diagnostic and therapeutic process for patients with NSD.

Radiofrequency Coblation-Assisted Resection of Skull Base Neoplasms Using an Endoscopic Endonasal Approach.

OBJECTIVES: We describe our early experiences with resecting skull base tumors using a radiofrequency ablation-assisted endoscopic endonasal approach. Ninety-seven patients with skull base tumors who were admitted to the Otorhinolaryngology department at Shanghai Jiaotong University Affiliated Shanghai Sixth People's Hospital between January 2014 and December 2016 were operated on using a radiofrequency ablation-assisted endoscopic endonasal approach. Complete resection was achieved in all patients. This paper describes the operative technique and presents the degree of resection, complications, and early clinical outcomes. METHODS: We investigated the safety and feasibility of the technique and assessed preliminary treatment outcomes. RESULTS: No patients experienced a new neurological deficit, cerebrospinal fluid leak, or meningitis after surgery. No deaths related to skull base tumors were observed during the follow-up period (14-50 months). The volume of intraoperative blood loss was 100-1,200 mL (median 350 mL), the duration of operation was 40-510 min (median 180 min), and the hospital stay was 6-65 days (median 18). CONCLUSIONS: Our limited experience indicates that this technique is feasible and safe for complete resection of some skull base tumors in selected cases and in the future will have an increasing role to play in endoscopic sinonasal and skull base tumor dissection.

Efficacy and Timing of Neonatal Ear Correction Molding.

BACKGROUND AND AIM: Given the incidence of congenital auricular anomalies varies racially, this study aimed to investigate the efficacy and timing of ear correction molding in infants with auricular anomalies. MATERIALS AND METHODS: A total of 141 auricular anomalies of 100 infants less than 4 months of age were treated using the Earlimn molding system. Treatment outcomes were graded (three categories) in terms of auricular morphology. The efficacies and outcomes of modeling were evaluated in infants according to age and anomaly type. RESULTS: The mean age at which correction was initiated was 35.13 days of life, and the average treatment duration was 17.81 days. Of all anomalies, 86% were corrected. Both deformations and certain malformations were satisfactorily corrected. The outcomes of children with conchal crura and mixed anomalies were relatively poor. Although no differences in treatment efficiency were evident among the three age groups, infants < 3 weeks old required shorter treatment courses than those > 6 weeks old. The only complications were mild skin ulcers. CONCLUSIONS: Ear correction molding is remarkably effective for infants with auricular deformations/malformations. Molding efficacy depends on the type of anomaly. Initiation of molding at less than 6 weeks of age is essential to minimize treatment duration. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Rosiglitazone Improves Glucocorticoid Resistance in a Sudden Sensorineural Hearing Loss by Promoting MAP Kinase Phosphatase-1 Expression.

In this study, we investigated the role of MAP kinase phosphatase-1 (MKP-1) and rosiglitazone (RSG) in glucocorticoid resistance and glucocorticoid sensitivity, respectively, using a guinea pig model of lipopolysaccharide- (LPS-) induced sudden sensorineural hearing loss (SSHL). The pigs were divided into control, LPS, LPS+dexamethasone (DEX), LPS+RSG, and LPS+DEX+RSG groups. Their hearing was screened by auditory brainstem response measurement. Immunofluorescence staining was used to identify the location of MKP-1 in the inner ear. The expression levels of MKP-1 and the related proteins in the inner ear were detected using western blotting. The morphological changes in the cochlea were observed via hematoxylin-eosin staining. Severe hearing loss was observed in the LPS group, as opposed to the protection from hearing loss observed in the LPS+DEX+RSG group. A positive correlation was observed between MKP-1 expression levels and protection from hearing loss. RSG and DEX synergistically influenced inner ear inflammation. In conclusion, resistance of LPS-induced SSHL guinea pig models to glucocorticoids may result from impaired MKP-1 function in inner ear tissues, induced by glucocorticoids, impairing the inhibition of inflammation. Our findings present novel targets to develop potential therapeutics to treat inflammatory diseases of the inner ear.

Benign paroxysmal positional vertigo in children.

OBJECTIVE: To describe the clinical features of benign paroxysmal positional vertigo (BPPV) in children. DESIGN: A retrospective study. SETTING: Six children diagnosed with BPPV between March 2014 and March 2015 were retrospectively evaluated. BPPV was diagnosed using the Dix-Hallpike and supine roll tests and treated with either the modified Epley particle repositioning procedure or Lempert or Gufoni manoeuvre. Follow-up was performed at 1-week intervals until vertigo and nystagmus disappeared during positional testing. PARTICIPANTS: A total of six children were followed up for a period of 10-22 months. MAIN OUTCOME MEASURES: Clinical features such as history, nystagmus and symptoms of vertigo, dizziness and nausea. RESULTS: Six children were diagnosed with BPPV using positional testing and treated with the modified Epley or Lempert/Gufoni particle repositioning procedures. Four children were diagnosed with posterior canal BPPV, while the remaining two were diagnosed with horizontal canal BPPV. One girl reported a history of head trauma, one girl had a family history of vertigo, and one boy reported hearing loss in the same ear as that affected by BPPV. Overall, 83.33% of children (5/6) were completely relieved of vertigo following one treatment session. The remaining child was asymptomatic after two sessions. No child reported relapse of vertigo during the follow-up period. CONCLUSIONS: BPPV can be diagnosed accurately by taking a detailed medical history and by use of positional testing. BPPV in children can be successfully identified and treated.

Comparison of Acceptable Noise Level Generated Using Different Transducers and Response Modes.

The acceptable noise level (ANL) was defined by subtracting the background noise level (BNL) from the most comfortable listening level (MCL) (ANL = MCL - BNL). This study compared the ANL obtained through different methods in 20 Chinese subjects with normal hearing. ANL was tested with Mandarin speech materials using a loudspeaker or earphones, with each subject tested by himself or by the audiologist. The presentation and response modes were as follows: (1) loudspeaker with self-adjusted noise levels using audiometer controls (LS method); (2) loudspeaker with the subject signaling the audiologist to adjust speech and noise levels (LA method); (3) earphones with self-adjusted noise levels using audiometer controls (ES method); and (4) earphones with the subject signaling the audiologist to adjust speech and noise levels (EA method). ANL was calculated from three measurements with each method. There was no significant difference in the ANL obtained through different presentation modes or response modes sound. The correlations between ANL, MCL, and BNL obtained from each two methods were significant. In conclusion, the ANL in normal-hearing Mandarin listeners may not be affected by presentation modes such as a loudspeaker or earphones nor is it affected by self-adjusted or audiologist-adjusted response modes. Earphone audiometry is as reliable as sound field audiometry and provides an easy and convenient way to measure ANL.

Factor Analysis of Low-Frequency Repetitive Transcranial Magnetic Stimulation to the Temporoparietal Junction for Tinnitus.

Objectives. We investigated factors that contribute to suppression of tinnitus after repetitive transcranial magnetic stimulation (rTMS). Methods. A total of 289 patients with tinnitus underwent active 1 Hz rTMS in the left temporoparietal region. A visual analog scale (VAS) was used to assess tinnitus loudness. All participants were interviewed regarding age, gender, tinnitus duration, laterality and pitch, audiometric parameters, sleep, and so forth. The resting motor thresholds (RMTs) were measured in all patients and 30 age- and gender-matched volunteers. Results. With respect to different factors that contribute to tinnitus suppression, we found improvement in the following domains: shorter duration, normal hearing (OR: 3.25, 95%CI: 2.01-5.27, p = 0.001), and without sleep disturbance (OR: 2.51, 95%CI: 1.56-4.1, p = 0.005) adjusted for age and gender. The patients with tinnitus lasting less than 1 year were more likely to show suppression of tinnitus (OR: 2.77, 95%CI: 1.48-5.19, p = 0.002) compared to those with tinnitus lasting more than 5 years. Tinnitus patients had significantly lower RMTs compared with healthy volunteers. Conclusion. Active low-frequency rTMS results in a significant reduction in the loudness of tinnitus. Significant tinnitus suppression was shown in subjects with shorter tinnitus duration, with normal hearing, and without sleep disturbance.