Amygdala structural and functional reorganization as an indicator of affective dysfunction in patients with tinnitus.

The aim of this study was to systematically investigate structural and functional alterations in amygdala subregions using multimodal magnetic resonance imaging (MRI) in patients with tinnitus with or without affective dysfunction. Sixty patients with persistent tinnitus and 40 healthy controls (HCs) were recruited. Based on a questionnaire assessment, 26 and 34 patients were categorized into the tinnitus patients with affective dysfunction (TPAD) and tinnitus patients without affective dysfunction (TPWAD) groups, respectively. MRI-based measurements of gray matter volume, fractional anisotropy (FA), fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), degree centrality (DC), and functional connectivity (FC) were conducted within 14 amygdala subregions for intergroup comparisons. Associations between the MRI properties and clinical characteristics were estimated via partial correlation analyses. Compared with that of the HCs, the TPAD and TPWAD groups exhibited significant structural and functional changes, including white matter integrity (WMI), fALFF, ReHo, DC, and FC alterations, with more pronounced WMI changes in the TPAD group, predominantly within the left auxiliary basal or basomedial nucleus (AB/BM), right central nucleus, right lateral nuclei (dorsal portion), and left lateral nuclei (ventral portion containing basolateral portions). Moreover, the TPAD group exhibited decreased FC between the left AB/BM and left middle occipital gyrus and right superior frontal gyrus (SFG), left basal nucleus and right SFG, and right lateral nuclei (intermediate portion) and right SFG. In combination, these amygdalar alterations exhibited a sensitivity of 65.4% and specificity of 96.9% in predicting affective dysfunction in patients with tinnitus. Although similar structural and functional amygdala remodeling were observed in the TPAD and TPWAD groups, the changes were more pronounced in the TPAD group. These changes mainly involved alterations in functionality and white matter microstructure in various amygdala subregions; in combination, these changes could serve as an imaging-based predictor of emotional disorders in patients with tinnitus.

Comparative analysis of vestibular endolymphatic hydrops grading methods and hearing loss in Ménière's disease: a retrospective MRI study using 3D-real inversion recovery sequence.

PURPOSE: To compare the correlation between different grading methods of vestibular endolymphatic hydrops (EH) and the severity of hearing loss in Ménière's disease (MD), and evaluate the diagnostic value of these methods in diagnosing MD. METHODS: This retrospective study included 30 patients diagnosed with MD from June 2021 to August 2023. All patients underwent inner ear MR gadolinium-enhanced imaging using three-dimensional (3D)-real inversion recovery sequences and pure-tone audiometry. The EH levels were independently evaluated according to the classification methods outlined by Nakashima et al. (Acta Otolaryngol Suppl 5-8, 2009. https://doi.org/10.1080/00016480902729827 ) (M1), Fang et al. (J Laryngol Otol 126:454-459, 2012. https://doi.org/10.1017/S0022215112000060 ) (M2), Barath et al. (Am J Neuroradiol 35:1387-1392, 2014. https://doi.org/10.3174/ajnr.A3856 ), (M3), Liu et al. (Front Surg 9:874971, 2022. https://doi.org/10.3389/fsurg.2022.874971 ), (M4), and Bernaerts et al. (Neuroradiology 61:421-429, 2019. https://doi.org/10.1007/s00234-019-02155-7 ) (M5), with a subsequent comparison of interobserver agreement. After achieving a consensus, an analysis was performed to explore the correlations between vestibular EH grading using different methods, the average hearing thresholds at low-mid, high-, and full frequencies and clinical stages. The diagnostic capabilities of these methods for MD were then compared. RESULTS: The interobserver consistency of M2-M5 was superior to that of M1. The EH grading based on M4 showed a significant correlation with the average hearing thresholds at low-mid, high-, and full frequencies and clinical stages. M1, M2, M3, and M5 correlated with some parameters. A receiver operating characteristic curve analysis indicated that M5 significantly outperformed M1, M2, M3, and M4 in terms of diagnostic efficiency for MD. CONCLUSION: M4 showed the strongest correlation with the degree of hearing loss in patients with MD, whereas M5 showed the highest diagnostic performance.

CT evaluation of unilateral pulsatile tinnitus with jugular bulb wall dehiscence.

OBJECTIVES: To investigate the imaging features of unilateral pulsatile tinnitus (PT) with jugular bulb wall dehiscence (JBWD). METHODS: Computerized tomography angiography images of unilateral PT patients were reviewed between 2019 and 2021. Thirty-one symptomatic JBWD patients without sigmoid sinus wall dehiscence (SSWD) were included. Thirty-eight patients with SSWD were used as the control group. The prevalence of JBWD was calculated. The area and height of the jugular bulb, the extent of dehiscence, the presence of jugular bulb diverticulum, posterior condylar emissary vein (PCEV), oblique occipital sinus (OOS), venous outflow laterality (VOL), the degree of transverse sinus stenosis (TSS), and the pituitary height to sella turcica ratio were compared between the two groups. RESULTS: The prevalence of JBWD was 12.1%, and JBWD was established as a causative diagnosis in 5.0% of unilateral PT patients. There were no statistical differences in the gender, symptomatic side, or VOL between the two groups. The area of the jugular bulb was larger and the height was higher (parea < 0.001, pheight = 0.005). The prevalence of jugular bulb diverticulum was higher in the JBWD group (p = 0.002). The degree of symptomatic TSS was less severe (p < 0.001), and the prevalence of bilateral TSS was lower in the JBWD group (p < 0.001). The pituitary height to sella turcica ratio was greater (p = 0.004), the prevalence of PCEV (p = 0.014) was lower, and OOS (p = 0.015) was greater in the JBWD group. CONCLUSIONS: The correlating factors of PT with JBWD and PT with SSWD are significantly different. These findings can further facilitate early and efficient PT treatment. KEY POINTS: • The incidence of jugular bulb dehiscence (JBWD) accounted for approximately 12.1% in pulsatile tinnitus (PT) patients, and JBWD was established as a causative diagnosis in 5.0% of PT patients. • PT required large blood flows and abnormal flow patterns, whether in JBWD or sigmoid sinus wall dehiscence groups. • JBWD causing PT has some unique characteristic findings on CT.

Adenovirus-mediated SIRT1 protects cochlear strial marginal cells in a D-gal-induced senescent model in vitro.

BACKGROUND: A primary obstacle in age-related hearing loss (ARHL) study is the lack of accelerated senescent models in vitro that explore the precise underlying mechanism in different types of ARHL. The damage to strial marginal cells (SMCs) is a subset of strial presbycusis-associated pathological changes. We aimed to establish a D-galactose (D-gal)-induced SMCs senescent model and study the effect of deacetylase sirtuin 1 (SIRT1) on presbycusis in vitro. METHODS: SMCs from C57BL/6J neonatal mice were cultured and treated with D-gal to establish accelerated senescent models. And then D-gal-induced SMCs were transfected with adenovirus (Ad)-SIRT1-GFP or Ad-GFP. Oxidative stress and mitochondrial DNA (mtDNA) damage were determined by histological analysis or RT-PCR. Western blotting (WB) and RT-PCR were used to evaluate protein and mRNA levels of superoxide dismutase 2 (SOD2) and SIRT1, respectively. Additionally, apoptosis was investigated by WB and TUNEL staining. RESULTS: D-gal-induced SMCs exhibited several characteristics of senescence, including increased the level of 8-hydroxy-2'-deoxyguanosine, which is a marker of DNA oxidative damage, and elevated the amount of mtDNA 3860-bp deletion, which is a common type of mtDNA damage in the auditory system of mice. SIRT1 overexpression effectively inhibited these changes by upregulating the level of SOD2, thereby inhibiting cytochrome c translocation from mitochondria to cytoplasm, inhibiting cell apoptosis, and ultimately delaying aging in the D-gal-induced senescent SMCs. CONCLUSIONS: Altogether, the evidence suggests that the D-gal-induced SMCs accelerated aging model is successfully established, and SIRT1 overexpression protects SMCs against oxidative stress by enhancing SOD2 expression in ARHL.

SIRT3-mediated deacetylation protects inner hair cell synapses in a H2O2-induced oxidative stress model in vitro.

Oxidative stress is considered a driving event in the damage to inner hair cell (IHC) synapses. Mitochondrial deacetylase sirtuin 3 (SIRT3) is an important regulator of reactive oxygen species (ROS) production. However, the effect of SIRT3 on IHC synapses remains elusive. In this study, we treated cochlear basilar membrane (CBM) with hydrogen peroxide (H2O2) to establish an oxidative stress model in vitro. The H2O2-induced CBM exhibited decreased the number of IHC synapses with low levels of ATP and mitochondrial membrane potential. Additionally, H2O2-induced CBM showed markedly reduced levels of forkhead box protein O 3a (FOXO3a), superoxide dismutase 2 (SOD2), and isocitrate dehydrogenase 2 (IDH2), thereby increasing ROS generation. SIRT3 overexpression via administrating nicotinamide riboside in the H2O2-induced CBM protected IHC synapses against oxidative stress and inhibited hair cell apoptosis. We further demonstrated that SIRT3 overexpression led to upregulation of IDH2, and hypoacetylation of several proteins, such as FOXO3a and SOD2, which in turn reduced the levels of ROS and improved mitochondrial function. Collectively, these findings reveal that overexpressing SIRT3 may be a potential therapeutic approach for damaged IHC synapses induced by oxidative stress.

The association between nasal mucosa bacteria and serum metals in children with nasal diseases.

Allergic rhinitis (AR) and adenoid hypertrophy (AH) are common nasal diseases in children. Studies have shown that heavy metals are environmental risk factors for nasal diseases, and the pathogenic mechanisms may be related to dysregulation of nasal mucosal microbiota. However, it is unclear how heavy metal exposure relates to the nasal mucosal microbiota in nasal diseases. Therefore, we explored serum metal exposure levels and nasal mucosal microbiota composition in children with different nasal disease, and further studied the potential correlation between metal exposure and disease-related taxa. There were 64 children recruited for this study. The 23 metals concentrations in serum were measured by inductively coupled plasma mass spectrometry, and nasal mucosal bacteria was identified by 16S rRNA sequencing. Nasal diseases (AR and AH) in children were associated with alterations in the abundance and diversity of the nasal mucosal microbiota. The nasal microbiota of children with AR showed lower diversity, while the microbiota of children with AH showed higher diversity. Linear discriminant analysis Effect Size showed 108 differentially abundant taxa between AR and control groups, 35 differentially abundant taxa among large adenoid, moderate adenoid and small adenoid groups. The serum zinc concentration was negatively correlated with Pielou's eveness index and Simpson's Index in children classified by adenoid size. The spearman correlation analysis showed that multiple disease-related taxa were closely associated with metal concentrations in serum. Our findings may support a link between metal exposure and the diversity and composition of nasal bacteria in children with nasal disease, which present new evidence for the effects of metals on children health.

AAV-ie-mediated UCP2 overexpression accelerates inner hair cell loss during aging in vivo.

BACKGROUND: Uncoupling protein 2 (UCP2), activated by excessive reactive oxygen species (ROS) in vivo, has the dual effect of reducing ROS to protect against oxidative stress and reducing ATP production to regulate cellular metabolism. Both the UCP2 and ROS are increased in cochleae in age-related hearing loss (ARHL). However, the role of UCP2 in sensory hair cells in ARHL remains unclear. METHODS: Male C57BL/6 J mice were randomly assigned to an 8-week-old group (Group 1), a 16-week-old group (Group 2), a 16-week-old + adeno-associated virus-inner ear (AAV-ie) group (Group 3), and a 16-week-old + AAV-ie-UCP2 group (Group 4). Mice aged 8 weeks were administrated with AAV-ie-GFP or AAV-ie-UCP2 via posterior semicircular canal injection. Eight weeks after this viral intervention, hearing thresholds and wave-I amplitudes were tested by auditory brainstem response (ABR). Subsequently, the cochlear basilar membrane was dissected for investigation. The number of hair cells and inner hair cell (IHC) synapses, the level of ROS, and the expression of AMP-activated protein kinase α (AMPKα), were assessed by immunofluorescence staining. In addition, mitochondrial function was determined, and the expression of AMPKα and UCP2 proteins was further evaluated using western blotting. RESULTS: Mice with early-onset ARHL exhibited enhanced oxidative stress and loss of outer hair cells and IHC synapses, while UCP2 overexpression aggravated hearing loss and cochlear pathophysiological changes in mice. UCP2 overexpression resulted in a notable decrease in the number of IHCs and IHC synapses, caused ATP depletion and excessive ROS generation, increased AMPKα protein levels, and promoted IHC apoptosis, especially in the apical and middle turns of the cochlea. CONCLUSION: Collectively, our data suggest that UCP2 overexpression may cause mitochondrial dysfunction via energy metabolism, which activates mitochondrion-dependent cellular apoptosis and leads to IHC loss, ultimately exacerbating ARHL.

Distinct brain structural-functional network topological coupling explains different outcomes in tinnitus patients treated with sound therapy.

Topological properties, which serve as the core of the neural network, and their couplings can reflect different therapeutic effects in tinnitus patients. We hypothesized that tinnitus patients with different outcomes after sound therapy (narrowband noise) would have distinct brain network topological alterations. Diffusion tensor imaging and resting-state functional magnetic resonance imaging (fMRI) were prospectively performed in 60 patients with idiopathic tinnitus and 57 healthy controls (HCs). Graph-theoretical network analyses of structural connectivity (SC), functional connectivity (FC), and SC and FC coupling were performed. Associations between clinical performance and graph-theoretical features were also analyzed. Treatment was effective (effective group; EG) in 28 patients and ineffective (ineffective group; IG) in 32 patients. For FC, the patients in the EG showed higher local efficiency than patients in the IG. For SC, patients in both the EG and IG displayed lower normalized characteristic path length, characteristic path length, and global efficiency than the HCs. More importantly, patients in the IG had higher coupling than the HCs, whereas there was no difference in coupling between patients in the EG and HCs. Additionally, there were significant associations between the SC features and clinical performance in patients in the EG. Our findings demonstrate that tinnitus patients exhibited significant brain network topological alterations, especially in the structural brain network. More importantly, patients who demonstrated different curative effects showed distinct SC-FC topological coupling properties. SC-FC coupling could be an indicator that could be used to predict prognoses in patients with idiopathic tinnitus before sound therapy.

ROS-Induced Oxidative Damage and Mitochondrial Dysfunction Mediated by Inhibition of SIRT3 in Cultured Cochlear Cells.

Sensorineural hearing loss (SNHL) is one of the most common causes of disability worldwide. Previous evidence suggests that reactive oxygen species (ROS) may play an important role in the occurrence and development of SNHL, while its mechanism remains unclear. We cultured dissected organs of Corti in medium containing different concentrations (0, 0.25, 0.5, 0.75, 1, and 1.25 mM) of hydrogen peroxide (H2O2) and established a four-concentration model of 0, 0.5, 0.75, and 1 mM to study different degrees of damage. We examined ROS-induced mitochondrial damage and the role of sirtuin 3 (SIRT3). Our results revealed that the number of ribbon synapses and hair cells appeared significantly concentration-dependent decrease with exposure to H2O2. Outer hair cells (OHCs) and inner hair cells (IHCs) began to be lost, and activation of apoptosis of hair cells (HCs) was observed at 0.75 mM and 1 mM H2O2, respectively. In contrast with the control group, the accumulation of ROS was significantly higher, and the mitochondrial membrane potential (MMP) was lower in the H2O2-treated groups. Furthermore, the expression of SIRT3, FOXO3A, and SOD2 proteins declined, except for an initial elevation of SIRT3 between 0 and 0.75 mM H2O2. Administration of the selective SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine resulted in increased damage to the cochlea, including loss of ribbon synapses and hair cells, apoptosis of hair cells, more production of ROS, and reduced mitochondrial membrane potential. Thoroughly, our results highlight that ROS-induced mitochondrial oxidative damage drives hair cell degeneration and apoptosis. Furthermore, SIRT3 is crucial for preserving mitochondrial function and protecting the cochlea from oxidative damage and may represent a possible therapeutic target for SNHL.

Myoelectric characteristics of tensor palatini and collapsibility of upper airway in OSA patients with different phenotypes under DISE.

OBJECTIVE: This study aims to evaluate the combination of myoelectric characteristics of tensor palatini muscle (TP) and collapsibility of upper airway in obstructive sleep apnea (OSA) patients with different external phenotypes of collapse pattern at velum level under drug-induced sleep endoscopy (DISE). STUDY DESIGN: Case series with planned data collection. SETTING: Operation room. SUBJECTS AND METHODS: 36 mainly collapse pattern at velum level OSA subjects underwent DISE with synchronous tensor palatini electromyograms (TP EMG), and polysomnography (ALICE 6). According to the phenotype of collapse pattern at velum level in DISE, the subjects were divided into group 1 (concentric collapse), group 2 (anteroposterior collapse), and group 3 (lateral collapse). Each group consisted of 13, 14, and 9 subjects, respectively, and was observed the electromyographic indexes at awake, sleep onset, during apnea and the third respiratory cycle after apnea. The active and passive upper airway critical closing pressure (Pcrit) of each group were measured at the same time, and the difference of neuromuscular response between different groups was evaluated. RESULTS: In tonic TPEMG, group 1 showed the highest value during awake and sleep onset, while group 2 was the highest during apnea and after apnea. In peak TPEMG, group 1 showed the highest value during awake. Group 2 showed the highest value during other states. In passive Pcrit and D value (difference between passive Pcrit and active Pcrit), group 2 was the highest, while group 1 was the highest in active Pcrit. Difference was statistically significant. CONCLUSIONS: Under different states of awake, sleep onset, apnea and after apnea, the response force of tensor palatini muscle of OSA subjects with different phenotypes under DISE was different. Group 1 showed the highest EMG values only when awake and sleep onset, and it was most prone to collapse. Group 2 had the highest anatomical load (passive Pcrit) and the highest neuromuscular compensatory effect (D value).

Outcomes at 6 months are related to brain structural and white matter microstructural reorganization in idiopathic tinnitus patients treated with sound therapy.

This study aimed to explore brain structural and white matter microstructural reorganization in the early stage of tinnitus and identify brain alterations that contribute to its relief after 6 months of sound therapy. We studied 64 patients with idiopathic tinnitus, including 29 patients who were categorized into an effective group (EG) and 35 who were categorized into an ineffective group (IG) according to the 6-month follow-up improvement of the Tinnitus Handicap Inventory score, along with 63 healthy controls (HCs). All participants underwent structural and diffusion tensor imaging scanning on a 3-T magnetic resonance system. Differences in brain gray/white matter volume and white matter microstructure were evaluated using voxel-based morphometry analysis and tract-based spatial statistics among the three groups. Associations between brain reorganization and the improvement of tinnitus symptoms were also investigated. Compared with EG patients, IG patients experienced a significant gray matter volume decrease in the right middle frontal gyrus (MFG)/right precentral gyrus (PreCG). Meanwhile, both EG and IG patients showed significant changes (decrease or increase) in brain white matter integrity in the auditory-related or nonauditory-related white matter fiber tracts compared with HCs, while EG patients showed decreased axial diffusivity in the bilateral middle cerebellar peduncle (MCP) compared with IG patients. We combined the gray matter change of the MFG/PreCG and the white matter integrity of the bilateral MCP as an imaging indicator to evaluate the patient's prognosis and screen patients before treatment; this approach reached a sensitivity of 77.1% and a specificity of 82.8%. Our study suggests that there was a close relationship between brain reorganization and tinnitus improvement. The right MFG/PreCG and bilateral MCP may be indicators that can be used to predict prognoses in patients with idiopathic tinnitus and may be used to screen patients before sound therapy. These findings may provide new useful information that can lead to a better understanding of the tinnitus mechanism.

Pretreatment intranetwork connectivity can predict the outcomes in idiopathic tinnitus patients treated with sound therapy.

Previous studies demonstrated that brain morphological differences and distinct patterns of neural activation exist in tinnitus patients with different prognoses after sound therapy. This study aimed to explore possible differences in intrinsic network-level functional connectivity (FC) in patients with different outcomes after sound therapy (narrow band noise). We examined intrinsic FC using resting-state functional magnetic resonance imaging in 78 idiopathic tinnitus patients (including 35 effectively treated and 43 ineffectively treated) and 52 healthy controls (HCs) via independent component analysis. We also investigated the associations between the differences in FC and clinical variables. Analyses revealed significantly altered intranetwork connectivity in the auditory network (AUN) and some nonauditory-related networks in the EG/IG patients compared to HCs; compared with EG patients, IG patients showed decreased intranetwork connectivity in the anterior default mode network (aDMN) and AUN. Meanwhile, robust differences were also evident in internetwork connectivity between some nonauditory-related networks (salience network and executive control network; posterior default mode network and dorsal attention network) in the EG relative to IG patients. We combined intranetwork connectivity in the aDMN and AUN as an imaging indicator to evaluate patient outcomes and screen patients before treatment; this approach reached a sensitivity of 94.3% and a specificity of 76.7%. Our study suggests that tinnitus patients with different outcomes show distinct network-level functional reorganization patterns. Intranetwork connectivity in the aDMN and AUN may be indicators that can be used to predict prognoses in patients with idiopathic tinnitus and screen patients before sound therapy.

Effects of different morphologic abnormalities on hemodynamics in patients with venous pulsatile tinnitus: A four-dimensional flow magnetic resonance imaging study.

The effects of morphologic abnormalities, including sigmoid sinus wall dehiscence (SSWD), transverse sinus stenosis (TSS), and sigmoid sinus diverticulum (SSD), on hemodynamics in venous pulsatile tinnitus (PT) patients have not been established. The aim of this study was to evaluate the effects of SSWD, TSS, and SSD on the hemodynamics of transverse-sigmoid sinus in venous PT patients. This was a prospective study with 44 venous PT patients and 12 healthy controls. A 3 T/four-dimensional (4D) flow magnetic resonance imaging with fast field echo was used. Computed tomography arteriography/venography was used to assess ipsilateral SSWD, TSS, and SSD. Maximum velocity (Vmax ), average velocity (Vavg ), and average flow (Flowavg ) were measured. Blood flow patterns were independently assessed by three neuroradiologists. One-way analysis of variance or Kruskal-Wallis test was also used. On the symptomatic side, all patients had SSWD, 33 patients had TSS, and 22 patients had SSD. Compared with healthy controls, patients with TSS, without TSS, with SSD, and without SSD all showed higher Vmax (all p < 0.050), Vavg (all p < 0.050), and Flowavg (all p < 0.050). Patients with TSS showed higher Vmax (p < 0.050) and Vavg (p < 0.050) than those without TSS, and no significant difference in Flowavg was found between the two groups (p = 0.408). No significant differences in Vmax , Vavg , and Flowavg were found between patients with and without SSD (all p = 1.000). Jet-like flow in the stenosis and downstream of the stenosis was observed in all patients with TSS. Vortex in SSD was observed in 15 patients with SSD (68%). High blood velocity and flow may be characteristic markers of venous PT. SSWD may be a necessary condition for venous PT. TSS may further increase the blood velocity and form a jet-like flow. SSD may be related to vortex formation but had no significant effect on blood velocity and flow. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.

CT venography correlate of transverse sinus stenosis and venous transstenotic pressure gradient in unilateral pulsatile tinnitus patients with sigmoid sinus wall anomalies.

OBJECTIVES: To investigate the correlation between transverse sinus stenosis (TSS) and transstenotic pressure gradient (TPG) in unilateral pulsatile tinnitus (PT) patients with sigmoid sinus wall anomalies (SSWA). METHODS: Fifty-seven patients with unilateral venous PT were retrospectively included. All of them underwent CT venography and catheter manometry, accompanied with SSWA. The degree, length, shape (intrinsic/extrinsic/dysplasia), location (proximal/middle/distal, referring to the relative position of TSS and the Labbé vein junction) of TSS, the types of SSWA (dehiscence/diverticulum), and the degree of transverse sinus outflow laterality were assessed, and the correlations with ipsilesional TPG were analyzed. RESULTS: The mean value of ipsilesional TPG was 7.61 ± 0.52 mmHg. The degree and length of ipsilesional TSS were positively correlated with TPG (p < 0.001, p' < 0.001), respectively. TPG was significantly larger in patients with contralateral transverse sinus dysplasia than those without (p = 0.023) and significantly smaller in patients with ipsilesional sigmoid sinus diverticulum than those with isolated dehiscence (p = 0.001). No statistical difference in TPG was shown between ipsilesional TSSs of different shapes or locations (p > 0.05). No correlation was noted between the degree of ipsilesional transverse sinus outflow laterality and TPG (p = 0.051). Stepwise linear regression indicated that the degree (ß = 9.207, 95% CI = 3.558-14.856), length (ß = 0.122, 95% CI = 0.025-0.220) of ipsilesional TSS, and contralateral transverse sinus dysplasia (ß = 1.875, 95% CI = 0.220-3.530) were significantly correlated with TPG (R2 = 0.471). CONCLUSIONS: The degree, length of ipsilesional TSS, and contralateral transverse sinus dysplasia may be used to predict TPG in unilateral PT patients with SSWA. KEY POINTS: • CT venography may act as a screening tool to help low-probability unilateral pulsatile tinnitus (PT) patients with sigmoid sinus wall anomalies (SSWA) avoid invasive catheter manometry. • The degree and length of ipsilesional transverse sinus stenosis (TSS) are positively correlated with transtenotic pressure gradient (TPG) in unilateral PT patients with SSWA. • Ipsilesional TPG is larger in unilateral PT patients with contralateral transverse sinus dysplasia than those without and is smaller in unilateral PT patients with sigmoid sinus diverticulum than those with isolated dehiscence.

Why does unilateral pulsatile tinnitus occur in patients with idiopathic intracranial hypertension?

PURPOSE: To investigate the relevant factors of unilateral pulsatile tinnitus (PT) in patients with idiopathic intracranial hypertension (IIH) using CT. METHODS: CT angiography images of IIH patients with unilateral PT (n = 19), without PT (n = 13), and controls (n = 32) were reviewed. The characteristics including transverse sinus stenosis (TSS), venous outflow laterality (VOL), sigmoid sinus wall dehiscence (SSWD), and sigmoid sinus diverticulum (SSD) were quantitatively or/and qualitatively detected. VOL was compared between the symptomatic side of IIH patients with PT and the larger side of IIH patients without PT and the controls. TSS, SSWD, and SSD were compared between the symptomatic side of IIH patients with PT, and both sides of the latter two groups. RESULTS: There was no statistical difference in body mass index or cerebrospinal fluid pressure between IIH patients with and without PT. The prevalence of TSS was significantly higher in IIH patients than that in the controls (p = 0.000), but TSS had no correlation with PT within IIH patients. The prevalence of SSWD successively decreased in IIH patients with PT, without PT, and the controls, with significant differences between each two of three groups (p = 0.000, p' = 0.000, p″ = 0.031). The proportion of VOL and the prevalence of SSD were significantly larger in IIH patients with PT than in the latter groups respectively (pVOL = 0.005, p'VOL = 0.000; pSSD = 0.040, p'SSD = 0.000). All SSDs in IIH patients with PT were accompanied with SSWD. CONCLUSION: The dominant VOL and ipsilateral SSWD with/without SSD may be correlated with the occurrence of unilateral PT in IIH patients.

Predicting outcome of velopharyngeal surgery in drug-induced sleep endoscopy by traction velum.

BACKGROUND: Outcomes of surgical management of obstructive sleep apnea-hypopnea syndrome (OSAHS) can be difficult to predict preoperatively. AIMS/OBJECTIVES: To study the effect of applying traction to the velum during drug-induced sleep endoscopy (DISE) in OSAHS patients, and to describe the use of traction velum in predicting surgical success. MATERIALS AND METHODS: 41 adult surgical patients with OSA (Friedman tongue position II and III) were evaluated by DISE. All patients subsequently underwent velopharyngeal surgery in the form of uvulopalatopharyngoplasty with tonsillectomy plus barbed reposition pharyngoplasty. RESULTS: Surgical responders (n = 26, 63.4%) and nonresponders (n = 15, 36.6%) demonstrated no significant differences with regard to preoperative AHI, age, sex, body mass index, and mean/lowest O2 saturation. Responders had a marked decrease in desaturation events (2.96 vs 0.03, p < 0.001) and percentage change in number of desaturation events before/after traction velum (56.7 vs 4.5, p < 0.001). Regression analysis revealed that reduction in mean desaturation events, with traction velum, by a percentage > 26.8% (odds ratio [OR] 1.046; 95% confidence interval [CI] 1.018-1.075; p = 0.001) was the only independent predictor of surgery success. CONCLUSIONS AND SIGNIFICANCE: OSAHS patients' velopharyngeal surgical outcome can be predicted by measuring the percentage change in the number of oxygen desaturation events before and after traction velum in DISE.

D-Galactose-induced oxidative stress and mitochondrial dysfunction in the cochlear basilar membrane: an in vitro aging model.

The cochlear basilar membrane (CBM) contains inner hair cells and outer hair cells that convert sound waves into electrical signals and transmit them to the central auditory system. Cochlear aging, the primary reason of age-related hearing loss, can reduce the signal transmission capacity. There is no ideal in vitro aging model of the CBM. In this study, we cultured the CBM, which was dissected from the cochlea of the C57BL/6 mice 5 days after birth, in a medium containing 20 mg/mL, 40 mg/mL, or 60 mg/mL D-galactose (D-gal). Compared with the control group, the levels of senescence-associated ß-galactosidase were increased in a concentration-dependent manner in the CBM of the D-gal groups. In addition, levels of the mitochondrial superoxide and patterns of an age-related mitochondrial DNA3860-bp deletion were significantly increased. The ATP levels and the membrane potential of the mitochondrial were significantly decreased in the CBM of the D-gal groups compared with the control group. Furthermore, in comparison with the control group, damaged hair cell stereocilia and a loss of inner hair cell ribbon synapses were observed in the CBM of the D-gal groups. A loss of hair cells and activation of caspase-3-mediated outer hair cell apoptosis were also observed in the CBM of the high-dose D-gal group. These insults induced by D-gal in the CBM in vitro were similar to the ones that occur in cochlear natural aging in vivo. Thus, we believe that this is a successful in vitro aging model using cultured CBM. These results demonstrate the effects of mitochondrial oxidative damage on presbycusis and provide a reliable aging model to study the mechanisms of presbycusis in vitro.

Loss of Cochlear Ribbon Synapse Is a Critical Contributor to Chronic Salicylate Sodium Treatment-Induced Tinnitus without Change Hearing Threshold.

Tinnitus is a common auditory disease worldwide; it is estimated that more than 10% of all individuals experience this hearing disorder during their lifetime. Tinnitus is sometimes accompanied by hearing loss. However, hearing loss is not acquired in some other tinnitus generations. In this study, we injected adult rats with salicylate sodium (SS) (200 mg/kg/day for 10 days) and found no significant hearing threshold changes at 2, 4, 8, 12, 14, 16, 20, or 24 kHz (all p > 0.05). Tinnitus was confirmed in the treated rats via Behaviour Testing of Acoustic Startle Response (ASR) and Gap Prepulse Inhibition Test of Acoustic Startle Reflex (GPIAS). A immunostaining study showed that there is significant loss of anti-CtBP2 puncta (a marker of cochlear inner hair cell (HC) ribbon synapses) in treated animals in apical, middle, and basal turns (all p < 0.05). The ABR wave I amplitudes were significantly reduced at 4, 8, 12, 14, 16, and 20 kHz (all p < 0.05). No significant losses of outer HCs, inner HCs, or HC cilia were observed (all p > 0.05). Thus, our study suggests that loss of cochlear inner HC ribbon synapse after SS exposure is a contributor to the development of tinnitus without changing hearing threshold.

Isolation and characterization of endothelial colony-forming cells from mononuclear cells of rat bone marrow.

Transplantation of bone marrow-derived endothelial progenitor cells (BM-EPCs) has been used as a therapeutic strategy for vascular repair. However, it remains controversial whether BM-EPCs exhibit clonal endothelial colony-forming cell (ECFC) capacity, a characteristic of true EPCs. The aim of this study was to isolate and explore the cellular properties of BM-ECFCs. We isolated BM-ECFCs from rat bone marrow with high purity via an optimized method. This approach involved the removal of selective colonies based on the conventional differential adhesive culture method used to isolate ECFCs from peripheral and umbilical cord blood. Our results indicate that primary colony BM-ECFCs display a panel of surface antigen markers consistent with endothelial cells. These BM-ECFCs coexpress CD34, CD133, and VEGFR2 at high levels, and these levels decrease with passaging. These cells have high potential for proliferation, migration, and formation of capillary-like structures on Matrigel, and these abilities are retained during ex vivo expansion. Furthermore, BM-ECFCs cultured with 10% or 20% fetal bovine serum demonstrated two different patterns of spontaneous capillary-like structure formation. These results provide a foundation for isolation of ECFCs from human bone marrow for autologous cell transplantation and tissue engineering applications in the future.

Temporal bone contrast-enhanced high-resolution CT evaluation of pulsatile tinnitus after sigmoid sinus wall reconstruction.

BACKGROUND: Sigmoid sinus wall reconstruction (SSWR) is a proven effective treatment for pulsatile tinnitus (PT) caused by sigmoid sinus wall dehiscence (SSWD) with or without sigmoid sinus diverticulum (SSD); however, comprehensive analysis of the postoperative imaging manifestations has not yet been reported. PURPOSE: To analyze temporal bone computed tomography (CT) imaging features following SSWR in patients with PT. MATERIAL AND METHODS: Following SSWR, temporal bone contrast-enhanced high-resolution CT (HRCT) images from 33 PT cases were retrospectively analyzed. Patients were divided into two groups based on follow-up interval: a short-interval group (≤18 months, 12 cases) and a long-interval group (>18 months, 21 cases). The mending material density and morphology was analyzed. Postoperative changes of the venous sinus were evaluated. Imaging manifestations of the normal temporal bone and mastoid air cells adjacent to the operative field were observed. RESULTS: The order of CT values of mending materials was significantly lower in the short-interval group than in the long-interval group (Z = -4.716, P < 0.001); the incidence of complete newly remodeled cortical bone on the rim of the mending materials was significantly higher in the long-interval group than in the short-interval group ( P < 0.001). Eleven patients (33.3%) showed varying degrees of remnant SSWD. The mending materials and normal mastoid bone structure showed complete fusion (n = 12, 36.4%), partial fusion (n = 16, 48.5%), or complete separation (n = 5, 15.2%). CONCLUSION: Temporal bone contrast-enhanced HRCT can be used to observe imaging features of the mending materials, venous sinus, adjacent normal temporal bone and mastoid air cells following SSWR.