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.

Distinct severity stages of obstructive sleep apnoea are correlated with unique dyslipidaemia: large-scale observational study.

BACKGROUND: Dyslipidaemia is an intermediary exacerbation factor for various diseases but the impact of obstructive sleep apnoea (OSA) on dyslipidaemia remains unclear. METHODS: A total of 3582 subjects with suspected OSA consecutively admitted to our hospital sleep centre were screened and 2983 (2422 with OSA) were included in the Shanghai Sleep Health Study. OSA severity was quantified using the apnoea-hypopnea index (AHI), the oxygen desaturation index and the arousal index. Biochemical indicators and anthropometric data were also collected. The relationship between OSA severity and the risk of dyslipidaemia was evaluated via ordinal logistic regression, restricted cubic spline (RCS) analysis and multivariate linear regressions. RESULTS: The RCS mapped a nonlinear dose-effect relationship between the risk of dyslipidaemia and OSA severity, and yielded knots of the AHI (9.4, 28.2, 54.4 and 80.2). After integrating the clinical definition and RCS-selected knots, all subjects were regrouped into four AHI severity stages. Following segmented multivariate linear modelling of each stage, distinguishable sets of OSA risk factors were quantified: low-density lipoprotein cholesterol (LDL-C), apolipoprotein E and high-density lipoprotein cholesterol (HDL-C); body mass index and/or waist to hip ratio; and HDL-C, LDL-C and triglycerides were specifically associated with stage I, stages II and III, and stages II-IV with different OSA indices. CONCLUSIONS: Our study revealed the multistage and non-monotonic relationships between OSA and dyslipidaemia and quantified the relationships between OSA severity indexes and distinct risk factors for specific OSA severity stages. Our study suggests that a new interpretive and predictive strategy for dynamic assessment of the risk progression over the clinical course of OSA should be adopted.

Elevated low-density lipoprotein cholesterol is independently associated with obstructive sleep apnea: evidence from a large-scale cross-sectional study.

BACKGROUND: Lipid metabolism disorder is recognized to be associated with obstructive sleep apnea (OSA); however, inconsistent results have been reported. The aim of this study was to evaluate the association between lipid profile and OSA with adjustments for multiple confounding factors. METHODS: In total, 2983 subjects were recruited from the Shanghai Sleep Health Study (SSHS) during 2007-2013. Data for overnight polysomnography (PSG) parameters, serum lipids, fasting blood glucose, insulin levels, and anthropometric measurements were collected. Multivariable logistic regression analyses were used to determine the correlation between lipid profile and OSA with adjustments for confounders including lipids, age, gender, Epworth sleepiness scale, body mass index, waist/hip ratio, glucose, insulin resistance, hypertension, and smoking. RESULTS: The prevalence of hyper total cholesterol (TC), hyper triglycerides, hypo high-density lipoprotein cholesterol, hyper low-density lipoprotein cholesterol (LDL-C), hyper apolipoprotein (apo) A-I, and hyper apoB differed significantly between the non-OSA and OSA patients. Without considering the interaction across different lipids, TC, LDL-C, and apoB were independently associated with OSA in primary multivariable logistic regression analyses; the odds ratios (ORs) and 95 % confidence intervals (CIs) were 1.262 (1.109-1.438), 1.432 (1.233-1.664), and 5.582 (2.643-11.787), respectively. However, only LDL-C (OR = 1.430, 95 % CI = 1.221-1.675) was found to be an independent risk factor for OSA in further multivariable logistic regression analyses. CONCLUSIONS: We demonstrated that patients with OSA had a higher percentage of dyslipidemia than subjects without OSA. Of the various components in serum lipid, only LDL-C was independently associated with OSA.

Slow dynamics of water confined in Newton black films.

Slowdown of translational and reorientational dynamics of water confined in Newton black films (NBFs) is revealed by molecular dynamics simulations. As a film becomes thinner, both translational and reorientational dynamics become slower. The polarization of water molecules in the macroscopic electrostatic field across the NBF and the coordination of Na(+) ions and surfactant anionic groups around water molecules concertedly lead to slowdown of water dynamics. The polarization effect is obvious for water not coordinated by Na(+) ions, which exhibits reorientational dynamics depending on initial dipole orientations. Na(+) ions and surfactant anionic groups retard dynamics of surrounding water by decreasing the hydrogen bond exchange probability and increasing the viscosity of water. The dependences of translational and reorientational dynamics on coordination environments of water are similar. Dynamics of water in positions close to the interfaces of NBFs are mainly retarded by Na(+) ions and surfactant anionic groups, while the macroscopic polarization effect plays the main role in influencing water dynamics in positions far from the interfaces. This study sheds light on the improvement of knowledge about the water dynamics slowdown mechanism in similar environments like reverse micelles and lamellar structures.

Temperature-dependent phase transition and desorption free energy of sodium dodecyl sulfate at the water/vapor interface: approaches from molecular dynamics simulations.

Adsorption of surfactants at the water/vapor interface depends upon their chemical potential at the interface, which is generally temperature-dependent. Molecular dynamics simulations have been performed to reveal temperature influences on the microstructure of sodium dodecyl sulfate (SDS) molecule adsorption layer. At room temperature, SDS molecules aggregate at the interface, being in a liquid-expanded phase, whereas they tend to spread out and probably transit to a gaseous phase as the temperature increases to above 318 K. This phase transition has been confirmed by the temperature-dependent changes in two-dimensional array, tilt angles, and immersion depths to the aqueous phase of SDS molecules. The aggregation of SDS molecules accompanies with larger immersion depths, more coordination of Na(+) ions, and less coordination of water. Desorption free energy profiles show that higher desorption free energy appears for SDS molecules at the aggregate state at low temperatures, but no energy barrier is observed. The shapes of desorption free energy profiles depend upon the distribution of SDS at the interface, which, in turn, is related to the phase state of SDS. Our study sheds light on the development of adsorption thermodynamics and kinetics theories.

Comparison of hearing results of malleovestibulopexy and total ossicular replacement prosthesis for chronic otitis media patients with a mobile stapes footplate.

OBJECTIVE: This study aimed to assess differences in hearing outcomes using the malleostapedotomy or malleovestibulopexy (MVP) and total ossicular replacement prosthesis (TORP) techniques in chronic otitis media patients with a mobile stapes footplate. STUDY DESIGN: Case series with planned data collection. SETTING: A university medical center. SUBJECTS AND METHODS: In total, 27 patients with chronic otitis media at the Sixth Hospital affiliated with Shanghai Jiao Tong University, between January and October 2010, were included. All patients had destruction of incus and stapes superstructures and a mobile stapes footplate. In all patients, surgery was performed under general anesthesia by a retroauricular approach. After the lesions were removed completely, ossicular reconstruction was performed using 1 of the techniques. In all patients, pure-tone audiograms were assessed before and 12 months after surgery. RESULTS: Thirteen patients underwent MVP surgery, whereas the other 14 cases received traditional TORP surgery. All patients showed improvements in functional hearing after surgery. Although the numbers of ears that had closure of the air-bone gap within 20 dB in the MVP group were not statistically significantly higher than those in the TORP group (Fisher's exact test, P > .05), the average postoperative gain of the MVP group was significantly higher than that of the TORP group (t test, P < .05). CONCLUSION: Functional hearing in chronic otitis media patients with a mobile stapes footplate was better in those who underwent MVP surgery than in those who underwent TORP surgery.

Applications of nanotechnology in remodeling the tumour microenvironment for glioblastoma treatment.

With the increasing research and deepening understanding of the glioblastoma (GBM) tumour microenvironment (TME), novel and more effective therapeutic strategies have been proposed. The GBM TME involves intricate interactions between tumour and non-tumour cells, promoting tumour progression. Key therapeutic goals for GBM treatment include improving the immunosuppressive microenvironment, enhancing the cytotoxicity of immune cells against tumours, and inhibiting tumour growth and proliferation. Consequently, remodeling the GBM TME using nanotechnology has emerged as a promising approach. Nanoparticle-based drug delivery enables targeted delivery, thereby improving treatment specificity, facilitating combination therapies, and optimizing drug metabolism. This review provides an overview of the GBM TME and discusses the methods of remodeling the GBM TME using nanotechnology. Specifically, it explores the application of nanotechnology in ameliorating immune cell immunosuppression, inducing immunogenic cell death, stimulating, and recruiting immune cells, regulating tumour metabolism, and modulating the crosstalk between tumours and other cells.

Harnessing Nanomedicine for Cartilage Repair: Design Considerations and Recent Advances in Biomaterials.

Cartilage injuries are escalating worldwide, particularly in aging society. Given its limited self-healing ability, the repair and regeneration of damaged articular cartilage remain formidable challenges. To address this issue, nanomaterials are leveraged to achieve desirable repair outcomes by enhancing mechanical properties, optimizing drug loading and bioavailability, enabling site-specific and targeted delivery, and orchestrating cell activities at the nanoscale. This review presents a comprehensive survey of recent research in nanomedicine for cartilage repair, with a primary focus on biomaterial design considerations and recent advances. The review commences with an introductory overview of the intricate cartilage microenvironment and further delves into key biomaterial design parameters crucial for treating cartilage damage, including microstructure, surface charge, and active targeting. The focal point of this review lies in recent advances in nano drug delivery systems and nanotechnology-enabled 3D matrices for cartilage repair. We discuss the compositions and properties of these nanomaterials and elucidate how these materials impact the regeneration of damaged cartilage. This review underscores the pivotal role of nanotechnology in improving the efficacy of biomaterials utilized for the treatment of cartilage damage.

Rejuvenating Hyaline Cartilaginous Phenotype of Dedifferentiated Chondrocytes in Collagen II Scaffolds: A Mechanism Study Using Chondrocyte Membrane Nanoaggregates as Antagonists.

Joint cartilage lesions affect the global population in the current aging society. Maintenance and rejuvenation of articular cartilage with hyaline phenotype remains a challenge as the underlying mechanism has not been completely understood. Here, we have designed and performed a mechanism study using scaffolds made of type II collagen (Col2) as the 3D cell cultural platforms, on some of which nanoaggregates comprising extracts of chondrocyte membrane (CCM) were coated as the antagonist of Col2. Dedifferentiated chondrocytes were, respectively, seeded into these Col2 based scaffolds with (antCol2S) or without (Col2S) CCM coating. After 6 weeks, in Col2S, the chondrocytes were rejuvenated to regain hyaline phenotype, whereas this redifferentiation effect was attenuated in antCol2S. Transcriptomic and proteomic profiling indicated that the Wnt/ß-catenin signaling pathway, which is an opponent to maintenance of the hyaline cartilaginous phenotype, was inhibited in Col2S, but it was contrarily upregulated in antCol2S due to the antagonism and shielding against Col2 by the CCM coating. Specifically, in antCol2S, since the coated CCM nanoaggregates contain the same components as those present on the surface of the seeded chondrocytes, the corresponding ligand sites on Col2 had been preoccupied and saturated by CCM coating before exposure to the seeded cells. The results indicated that the ligation between Col2 ligands and integrin α5 receptors on the surface of the seeded chondrocytes in antCol2S was antagonized by the CCM coating, which facilitates the Wnt/ß-catenin signaling toward the loss of hyaline cartilaginous phenotype. This finding reveals the contribution of Col2 for maintenance and rejuvenation of the hyaline cartilaginous phenotype in chondrocytes.

Cartilage Tissue Engineering in Practice: Preclinical Trials, Clinical Applications, and Prospects.

Articular cartilage defects significantly compromise the quality of life in the global population. Although many strategies are needed to repair articular cartilage, including microfracture, autologous osteochondral transplantation, and osteochondral allograft, the therapeutic effects remain suboptimal. In recent years, with the development of cartilage tissue engineering, scientists have continuously improved the formulations of therapeutic cells, biomaterial-based scaffolds, and biological factors, which have opened new avenues for better therapeutics of cartilage lesions. This review focuses on advances in cartilage tissue engineering, particularly in preclinical trials and clinical applications, prospects, and challenges.

Development of artificial bone graft via in vitro endochondral ossification (ECO) strategy for bone repair.

Endochondral ossification (ECO) is a form of bone formation whereby the newly deposited bone replaces the cartilage template. A decellularized artificial cartilage graft (dLhCG), which is composed of hyaline cartilage matrixes, has been developed in our previous study. Herein, the osteogenesis of bone marrow-derived MSCs in the dLhCG through chondrogenic differentiation, chondrocyte hypertrophy, and subsequent transdifferentiation induction has been investigated by simulating the physiological processes of ECO for repairing critical-sized bone defects. The MSCs were recellularized into dLhCGs and subsequently allowed to undergo a 14-day proliferation period (mrLhCG). Following this, the mrLhCG constructs were subjected to two distinct differentiation induction protocols to achieve osteogenic differentiation: chondrogenic medium followed by chondrocytes culture medium with a high concentration of fetal bovine serum (CGCC group) and canonical osteogenesis inducing medium (OI group). The formation of a newly developed artificial bone graft, ossified dLhCG (OsLhCG), as well as its capability of aiding bone defect reconstruction were characterized by in vitro and in vivo trials, such as mRNA sequencing, quantitative real-time PCR (qPCR), immunohistochemistry, the greater omentum implantation in nude mice, and repair for the critical-sized femoral defects in rats. The results reveal that the differentiation induction of MSCs in the CGCC group can realize in vitro ECO through chondrogenic differentiation, hypertrophy, and transdifferentiation, while the MSCs in the OI group, as expected, realize ossification through direct osteogenic differentiation. The angiogenesis and osteogenesis of OsLhCG were proved by being implanted into the greater omentum of nude mice. Besides, the OsLhCG exhibits the capability to achieve the repair of critical-size femoral defects.

Effect of Combining Sound Therapy with Pharmacotherapy on the Recovery of Hearing Abilities in the Case of Sudden Sensorineural Hearing Loss: A Prospective Study.

INTRODUCTION: This study investigated the effect of sound therapy combined with drug therapy (SDT) on gap detection threshold and speech recognition scores in patients with sudden sensorineural hearing loss (SSNHL). METHODS: Patients with SSNHL were grouped randomly into SDT and drug therapy (DT) groups. All patients received standard drug treatment and patients in the SDT group additionally received sound stimulation for the affected ears for 6 days. Pure tone audiogram, speech recognition scores at normal and time-compressed rates under quiet and noisy conditions, and the gap detection threshold of the SDT and DT groups before treatment and on day 6 and 30 after treatment were compared. RESULTS: There were 20 patients in the SDT group and 24 in the DT group. The pure tone thresholds of affected ears were significantly lower in the SDT group on day 6 after treatment than those in the DT group at 125 and 250 Hz. Significantly lower gap detection thresholds and higher speech recognition scores under noisy conditions were observed at the normal and time-compressed rates in the SDT group than those in the DT group on day 6 and 30 after treatment. Significant correlations were observed between the gap thresholds and speech recognition scores in a noisy environment at normal and time-compressed rates on day 6 and 30. CONCLUSIONS: SDT may improve the recovery of hearing abilities, such as the gap in noise thresholds and speech recognition in noise, in the case of SSNHL. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-17012262.

Biomaterial-based physical regulation of macrophage behaviour.

Macrophages play a critical role in regulating immune reactions induced by implanted biomaterials. They are highly plastic and in response to diverse stimuli in the microenvironment can exhibit a spectrum of phenotypes and functions. In addition to biochemical signals, the physical properties of biomaterials are becoming increasingly appreciated for their significant impact on macrophage behaviour, and the underlying mechanisms deserve more in-depth investigations. This review first summarises the effects of key physical cues - including stiffness, topography, physical confinement and applied force - on macrophage behaviour. Then, it reviews the current knowledge of cellular sensing and transduction of physical cues into intracellular signals. Finally, it discusses the major challenges in understanding mechanical regulation that could provide insights for biomaterial design.

Bletilla striata polysaccharide cryogel scaffold for spatial control of foreign-body reaction.

BACKGROUND: Implantation of a biomaterial may induce the foreign-body reaction to the host tissue that determines the outcome of the integration and the biological performance of the implants. The foreign-body reaction can be modulated by control of the material properties of the implants. METHODS: First, we synthesized methacrylated Bletilla striata Polysaccharide (BSP-MA) and constructed a series of open porous cryogels utilizing this material via the freezing-thawing treatment of solvent-precursors systems. Second, Pore size and modulus were measured to characterize the properties of BSP cryogels. Live/dead staining of cells and CCK-8 were performed to test the cytocompatibility of the scaffolds. In addition, the Real-Time qPCR experiments were carried for the tests. Finally, the BSP scaffolds were implanted subcutaneously to verify the foreign-body reaction between host tissue and materials. RESULTS: Our data demonstrated that cryogels with different pore sizes and modulus can be fabricated by just adjusting the concentration. Besides, the cryogels showed well cytocompatibility in the in vitro experiments and exhibited upregulated expression levels of pro-inflammation-related genes (Tnfa and Il1b) with the increase of pore size. In vivo experiments further proved that with the increase of pore size, more immune cells infiltrated into the inner zone of materials. The foreign-body reaction and the distribution of immune-regulatory cells could be modulated by tuning the material microstructure. CONCLUSIONS: Collectively, our findings revealed Bletilla striata polysaccharide cryogel scaffold with different pore sizes can spatially control foreign-body reaction. The microstructure of cryogels could differentially guide the distribution of inflammatory cells, affect the formation of blood vessels and fibrous capsules, which eventually influence the material-tissue integration. This work demonstrates a practical strategy to regulate foreign body reaction and promote the performance of medical devices.

Coagulation States in Patients With Sudden Sensorineural Hearing Loss Evaluated by Thromboelastography.

OBJECTIVE: The state of coagulation is controversial in patients with sudden sensorineural hearing loss (SSNHL). We used thromboelastography (TEG) to explore the relationships between blood coagulation parameters and SSNHL pathogenesis and recovery. STUDY DESIGN: Prospective study. SETTING: Affiliated Sixth People's Hospital, Shanghai Jiao Tong University. METHODS: A total of 104 newly diagnosed patients with SSNHL and 29 matched healthy controls were recruited. Hearing assessments, TEG, and conventional coagulation tests (CCTs) were performed, followed by standard treatments and follow-up. RESULTS: The TEG parameters of patients with SSNHL were in the normal range, but the group exhibited a significantly prolonged kinetic time (K; P = .004) and a smaller angle (P = .003) as compared with the controls. After grouping the patients with SSNHL according to audiograms and comparing them in pairs, we found that the differences were significant only when controls were compared with patients with low-frequency SSNHL (K, P = .023; angle, P = .04) and flat-type SSNHL (K, P = .017; angle, P = .014). Logistic regression analysis showed that neither TEG nor CCT parameters significantly affected hearing improvement after SSNHL treatment. CONCLUSIONS: Although the K value and angle were significantly increased and significantly reduced, respectively, in the test group as compared with the control group, the state of coagulation in patients with SSNHL was still within the normal range. No CCT or TEG coagulation parameters (except the angle) differed significantly among patients in each group according to hearing recovery status, which suggested that the coagulation status does not determine the prognosis of patients with SSNHL.

A phase-transfer catalyst-based nanoreactor for accelerated hydrogen sulfide bio-imaging.

Hydrogen sulfide (H2S) is an important signaling molecule in various biological processes; however, its real-time monitoring in living cells is hampered by long detection time for current fluorescent probes. To overcome this challenge, we designed a phase-transfer catalyst (PTC) approach to accelerate the reaction between the probe and the analyte by conjugating common fluorescent probes - mostly hydrophobic small molecules - with an amphiphilic PEG-PPG-PEG polymer, enabling the controllable assembly of H2S nanoprobes in an aqueous solution. The PEG block helps to establish a PTC microenvironment that endows the assembled nanoprobes with a significantly reduced detection time (3-10 min; versus 20-60 min for small-molecule probes). Based on this approach, we synthesised two nanoprobes of different wavelengths, DS-Blue-nano and DN-Green-nano, which can sensitively detect H2S in living macrophage cells with bright fluorescence starting at as early as 7 min and reaching stability at 15 min. These data suggest PTC-based nanoprobes as a new and generic approach for constructing sensitive fluorescent probes for the real-time imaging of H2S, and perhaps other molecules in future, under biological conditions.

Switching Tinnitus-On: Maps and source localization of spontaneous EEG.

OBJECTIVE: To identify the spectrotemporal changes and sources in patients that could "turn on" tinnitus with multichannel electroencephalography (EEG) system. METHODS: Multichannel EEG was recorded from six patients during the Tinnitus-On and Tinnitus-Off states. The EEG power spectrum and eLORETA-based sources were measured. RESULTS: There was a global increase in delta and theta during Tinnitus-On plus large changes in alpha 1 and alpha 2. During the Tinnitus-On state, many new sources in delta, theta, alpha 1 and gamma bands emerged in the opposite hemisphere in the inferior temporal gyrus (Brodmann area, BA 20), middle temporal gyrus (BA 21), lateral perirhinal cortex (BA 36), ventral entorhinal cortex (BA 28) and anterior pole of the temporal gyrus (BA 38). CONCLUSIONS: The emergence of new delta, theta and gamma band sources in the inferior temporal gyrus (BA 20), middle temporal gyrus (BA 21) and lateral perirhinal cortex (BA 36) plus the appearance of new delta and theta sources in the ventral entorhinal cortex (BA28) and anterior pole of the temporal lobe (BA 38) may comprise a network capable of evoking the phantom sound of tinnitus by simultaneously engaging brain regions involved in memory, sound recognition, and distress which together contribute to tinnitus severity. SIGNIFICANCE: The sudden appearance of new sources of activity in the opposite hemisphere within the inferior temporal gyrus, middle temporal gyrus and perirhinal cortex may initiate the perception of tinnitus perception.

Enhanced Near-Infrared Emission from Carbon Dots by Surface Deprotonation.

Carbon dots (CDs) with efficient excitation and emission in deep-red/near-infrared (NIR) spectral range are important for bioimaging applications. Herein, we develop a simple and effective method to significantly enhance both the absorption and emission of CDs in deep-red/NIR by suppressing nonradiative charge recombination via deprotonation of the CD surface. As compared to aqueous solutions at room temperature, NIR emission of CDs in N,N-dimethylformamide and glycerol experience a 50- and 70-fold increase at -20 °C, respectively, due to enhanced deprotonation ability and viscosity. On the basis of the adjustable NIR fluorescence intensity of CDs, multilevel data encryption in the NIR region is realized by controlling the humidity and the temperature of a CD-ink stamped paper.

In silico calculation of acidity constants of carbonic acid conformers.

In order to explore the aqueous acid chemistry of carbonic acid, we employ a constrained ab initio molecular dynamics (AIMD) technique to study acid dissociations of its three conformers including CC (cis-cis), CT (cis-trans), and TT (trans-trans). The simulations of reagent states reveal similar hydration characteristics for them: the hydroxyls donate H-bonds to solvating waters but no obvious H-bonding exists between hydroxyl oxygen atoms and waters. It is found that the CC conformer dissociates spontaneously to bicarbonate within picoseconds whereas the other two can stay for relatively long simulation times. This suggests that CC has the strongest acidity among the three conformers and it is not stable in water. The simulations indicate that the symmetrical hydroxyls of TT conformer have a pKa value of 3.11 and the two asymmetrical hydroxyls of CT show different pKa values: 2.60 and 3.75, respectively. Overall, these results confirm the recent experimental measurement: about 4.0 for deuterated carbonic acid. By analyzing the dissociation processes, it is revealed that the differences of the acid constants stem from the initial steps of hydroxyls stretches. This simulation study provides a quantitative and microscopic basis for better understanding the reactivity of aqueous carbonate species.

A New Proposal for Severity Evaluation of Menière's Disease by Using the Evidence From a Comprehensive Battery of Auditory and Vestibular Tests.

To date, no widely accepted criteria exist to quantify the severity of Menière's disease (MD) by using vestibular tests. This study aimed to compare association of hearing loss and vertigo severity with association of accurate assessments of vestibular function and the vertigo severity. The severity of vertigo was documented by a comprehensive medical history with number of vertigo attacks in the past 6 months and a Dizziness Handicap Inventory (DHI) questionnaire. The involvement of vestibular organs was verified by audio-vestibular tests in 80 definite MD patients. Correlations between DHI scores, number of vertigo attacks in the past 6 months, audio-vestibular function, and the number of involved vestibular end organs were evaluated. We show that there are no significant differences in either severity of vertigo or laboratory results across the degree of hearing loss. Furthermore, the number of involved vestibular end organs was significantly correlated with vestibulo-ocular reflex gain in anterior and posterior canal video head impulse test (vHIT), interaural asymmetry ratio in vestibular-evoked myogenic potentials (VEMPs), and number of vertigo attacks in the past 6 months and DHI score. The vestibulo-ocular reflex gain in the rotatory chair test (RCT) was significantly correlated with the DHI Physical scores and number of involved vestibular end organs at 0.08 Hz. These results indicate that hearing loss is a poor indicator of vertigo severity in MD whereas the number of involved vestibular end organs may serve as an objective measure for MD progress. A battery of vestibular tests targeting different sensor organs is a complementary method for evaluating inner ear deficits and may aid in "grading" the severity of MD.