Lipocalin-2 promotes adipose-macrophage interactions to shape peripheral and central inflammatory responses in experimental autoimmune encephalomyelitis.

OBJECTIVE: Accumulating evidence suggests that dysfunctional adipose tissue (AT) plays a major role in the risk of developing multiple sclerosis (MS), the most common immune-mediated and demyelinating disease of the central nervous system. However, the contribution of adipose tissue to the etiology and progression of MS is still obscure. This study aimed at deciphering the responses of AT in experimental autoimmune encephalomyelitis (EAE), the best characterized animal model of MS. RESULTS AND METHODS: We observed a significant AT loss in EAE mice at the onset of disease, with a significant infiltration of M1-like macrophages and fibrosis in the AT, resembling a cachectic phenotype. Through an integrative and multilayered approach, we identified lipocalin2 (LCN2) as the key molecule released by dysfunctional adipocytes through redox-dependent mechanism. Adipose-derived LCN2 shapes the pro-inflammatory macrophage phenotype, and the genetic deficiency of LCN2 specifically in AT reduced weight loss as well as inflammatory macrophage infiltration in spinal cord in EAE mice. Mature adipocytes downregulating LCN2 reduced lipolytic response to inflammatory stimuli (e.g. TNFα) through an ATGL-mediated mechanism. CONCLUSIONS: Overall data highlighted a role LCN2 in exacerbating inflammatory phenotype in EAE model, suggesting a pathogenic role of dysfunctional AT in MS.

Mutual spin-phonon driving effects and phonon eigenvector renormalization in nickel (II) oxide.

The physics of mutual interaction of phonon quasiparticles with electronic spin degrees of freedom, leading to unusual transport phenomena of spin and heat, has been a subject of continuing interests for decades. Despite its pivotal role in transport processes, the effect of spin-phonon coupling on the phonon system, especially acoustic phonon properties, has so far been elusive. By means of inelastic neutron scattering and first-principles calculations, anomalous scattering spectral intensity from acoustic phonons was identified in the exemplary collinear antiferromagnetic nickel (II) oxide, unveiling strong spin-lattice correlations that renormalize the polarization of acoustic phonon. In particular, a clear magnetic scattering signature of the measured neutron scattering intensity from acoustic phonons is demonstrated by its momentum transfer and temperature dependences. The anomalous scattering intensity is successfully modeled with a modified magneto-vibrational scattering cross-section, suggesting the presence of spin precession driven by phonon. The renormalization of phonon eigenvector is indicated by the observed "geometry-forbidden" neutron scattering intensity from transverse acoustic phonon. Importantly, the eigenvector renormalization cannot be explained by magnetostriction but instead, it could result from the coupling between phonon and local magnetization of ions.

Quantification of endolymphatic hydrops and its correlation with Meniere's disease clinical features.

OBJECTIVE: We aimed to quantitatively evaluate the degree of endolymphatic hydrops and its correlation with the clinical features of Meniere's disease. METHODS: We retrospectively collected data from patients with Meniere's disease who underwent gadolinium-enhanced magnetic resonance imaging (MRI) at our department from January 2018 to December 2019. Mimics software was used to perform three-dimensional modelling of the labyrinth, and volume information was obtained to calculate the endolymphatic hydrops index (EHI). A correlation analysis was conducted with data from pure tone audiometry, electrocochleography (EchoG), vestibular myogenic-evoked potential (VEMP) testing, caloric testing and video head impulse testing (vHIT). A two-dimensional method was also employed to calculate the hydrops ratio (HR) of cochlea and vestibule. The test-retest reliability of EHI/HR from different operators was evaluated. RESULTS: A total of 23 affected ears were examined, and the EHI was significantly correlated with Meniere's disease stage, low-frequency hearing threshold, EchoG summating potential/action potential ratio (-SP/AP) and VEMP binaural asymmetry ratio, but no significant correlation was observed between EHI and the caloric test or vHIT. The Intraclass correlation coefficient (ICC) of EHI data calculated by two otologists was 0.946 (p < .001). And the ICC of cochlea and vestibule HR were 0.844 and 0.832 (p < .001). CONCLUSION: Mimics software can be used to quantitatively evaluate the degree of endolymphatic hydrops and have shown higher test-retest reliability than traditional two-dimensional evaluation method. Endolymphatic hydrops correlates with clinical data, such as Meniere's disease stage, low-frequency hearing threshold, EchoG and VEMP asymmetry ratio.

Application and practice of a step-by-step method combined with case-based learning in Chinese otoendoscopy education.

BACKGROUND: Standardized training allows more physicians to master otoendoscopic surgery. However, the lecture-based learning (LBL) applied in otoendoscopy teaching may not be conducive to training students in clinical thinking and surgical ability. It is necessary to explore innovative methods for otoendoscopy teaching. This study aimed to determine the effect of a step-by-step (SBS) method combined with case-based learning (CBL) in otoendoscopy teaching. METHODS: Fifty-nine physicians who participated in otoendoscopy training were selected as the study subjects and randomly divided into two groups (A and B). Group A underwent training with the SBS & CBL method, while Group B underwent training with the LBL & CBL method. The effects of these two methods for otoendoscopy training were compared by evaluation of professional skills and questionnaires before and after the training. RESULTS: Proficiency in otoendoscopic anatomy and grades for both professional knowledge and otoendoscopic skills were significantly higher in Group A than in Group B(P < 0.05). In terms of learning interest, surgical ability, acting capacity during surgery, reducing surgical complications, and satisfaction with learning experience, all responses from Group A were better than those from Group B(P < 0.05). CONCLUSIONS: The SBS & CBL method may help to improve ability in otoendoscopic surgery and clinical thinking and appears suitable for endoscopy teaching.

Notched Sound Alleviates Tinnitus by Reorganization Emotional Center.

BACKGROUND: Tinnitus is a common disease, and sound therapy is an effective method to alleviate it. Previous studies have shown that notched sound not only changes levels of cortical blood oxygen, but affects blood oxygen in specific cerebral cortical areas, such as Brodmann area 46 (BA46), which is associated with emotion. Extensive evidence has confirmed that tinnitus is closely related to emotion. Whether notched sound plays a role in regulating the emotional center is still unclear. METHODS: This study included 29 patients with newly diagnosed chronic tinnitus who were treated with notched sound. Functional near-infrared spectroscopy (fNIRS) was conducted before and after treatment to observe bilateral changes in cortical blood oxygen in the cerebral hemispheres. We compared the changes in connectivity between the two regions of interest (the superior temporal gyrus and BA46), as wells as other cortical regions before and after treatment. RESULTS: The results showed (1) That global connectivity between the bilateral auditory cortex of the superior temporal sulcus and the ipsilateral cortex did not change significantly between baseline and the completion of treatment, and (2) That the connectivity between channel 14 and the right superior temporal sulcus decreased after treatment. The overall connectivity between the right BA46 region and the right cortex decreased after treatment, and decreases in connectivity after treatment were specifically found for channels 10 and 14 in the right parietal lobe and channels 16, 20, 21, and 22 in the frontal lobe, while there was no significant change on the left side. There were no significant changes in the questionnaire measures of tinnitus, anxiety, or depression before and after treatment. CONCLUSION: The results of the study indicate that cerebral cortex reorganization occurs in tinnitus patients after submitted to treatment with notched sound for 1 month, and that notched sound decreases the connectivity between the auditory cortex and specific brain regions. SIGNIFICANCE: Notched sound not only regulates the auditory center through lateral inhibition, but also alleviates tinnitus by reorganizing the emotional control center.

Observation of Magnon Polarons in a Uniaxial Antiferromagnetic Insulator.

Magnon polarons, a type of hybridized excitations between magnons and phonons, were first reported in yttrium iron garnet as anomalies in the spin Seebeck effect responses. Here, we report an observation of antiferromagnetic (AFM) magnon polarons in a uniaxial AFM insulator Cr_{2}O_{3}. Despite the relatively higher energy of magnon than that of the acoustic phonons, near the spin-flop transition of ∼6 T, the left-handed magnon spectrum shifts downward to hybridize with the acoustic phonons to form AFM magnon polarons, which can also be probed by the spin Seebeck effect. The spin Seebeck signal is founded to be enhanced due to the magnon polarons at low temperatures.

Combined application of single-energy metal artifact reduction and reconstruction techniques in patients with Cochlear implants.

BACKGROUND: The purpose of this study was to develop an effective method of reducing metal artifacts in cochlear implant (CI) electrodes. METHODS: The temporal bones of 30 patients (34 ears) after CI were examined with 320-detector row computed tomography, which was evaluated by two senior radiologists using a double-blind method. Noise, artifact index, signal-to-noise ratio, and the subjective image quality score were compared before versus after using single-energy metal artifact reduction (SEMAR). The electrode position, single electrode visibility, and electrode count were evaluated using SEMAR combined with either multi-planar reconstruction (MPR) or maximum intensity projection. RESULTS: The two radiologists' measurements had good consistency. SEMAR significantly reduced the image noise and artifacts index and significantly improved the signal-to-noise ratio and subjective image quality score (P < 0.01). The combination of SEMAR with MPR was conducive to accurate assessment of electrode position and single-electrode visibility. The combination of SEMAR with MIP facilitated accurate and intuitive matching of the assessed electrode count with the number of electrodes implanted during the operation (P = 0.062). CONCLUSION: SEMAR significantly reduces metal artifacts generated by CI electrodes and improves the quality of computed tomography images. The combination of SEMAR with MPR and maximum intensity projection is beneficial for evaluating the position and number of CI electrodes.

Chinese validation and clinical application of the tinnitus functional index.

OBJECTIVE: The Tinnitus Functional Index (TFI) is a new diagnostic measure of the functional impact of tinnitus that is also a sensitive measure of treatment-related changes. However, the TFI has not been translated into Chinese and fully validated in China. The aim of the present study was to evaluate the validity of a Chinese version of the TFI as a diagnostic measure of tinnitus severity in a sample of Chinese patients and to verify the value of its clinical application in China. DESIGN: A sample of 206 patients whose primary complaint was tinnitus was used to analyze the reliability and validity of the TFI. In addition, patients were asked to fill out the Tinnitus Handicap Inventory (THI) and the Center for Epidemiologic Studies-Depression Scale (CES-D), the Beck Anxiety Inventory (BAI), and the Satisfaction With Life Scale (SWLS) to compare TFI with their association. The internal consistency of the TFI was assessed with Cronbach's alpha coefficient. The factor structure of the TFI was assessed by Exploratory Factor Analysis (EFA). The extracted factors were compared to those of the original TFI scale. RESULTS: The reliability of the Chinese version of the TFI (Cronbach' s α = .969) showed high internal consistency. The exploratory factor analysis (EFA) of the TFI showed that six factors with one main factor could be extracted instead of eight factors as described in the original version. Nevertheless, relations to the original eight subscales could be demonstrated. A high correlation between the TFI and the THI (r = .865, p < 0.01) and lower correlations between the TFI and the CES-D (r = .334, p < 0.01), BAI (r = .559, p < 0.01), and SWLS (r = - 0.324, p < 0.01) confirmed the satisfactory convergent and discriminant validity of the TFI. CONCLUSION: After translated and validated a Chinese version of the TFI and found that the TFI had high reliability and validity, which means both instruments are reliable instruments to assess the severity of tinnitus in clinical applications in China.

Cortical Activation Patterns of Different Masking Noises and Correlation With Their Masking Efficacy, Determined by Functional Near-Infrared Spectroscopy.

Acoustic therapy in tinnitus treatment is poorly characterized, and efficacy assessment depends on subjective descriptions. Narrow-band noise, notched sound, and white noise have positive therapeutic effects on monotonous tinnitus. Considering the tonotopic characteristics of the auditory system and the spectral characteristics of these three masking sounds, the activation pattern of the auditory cortex and the mechanism of inhibiting tinnitus may be different. This study aimed to compare the activation patterns of three spectrally different masking noises and study the correlation between the masking effects and variational amplitude of oxygenated hemoglobin (HbO) in the corresponding cortical regions. We also assessed near-infrared spectroscopy brain function imaging (NIRS) as an objective assessment tool in acoustic therapy. Patients with persistent non-pulsatile tinnitus and control volunteers without tinnitus were enrolled in this study. The subjects were seated in a sound-proof room, with two optode arrays covering the bilateral temporal lobe. Auditory stimuli were presented; stimulation sequences followed the block design: different noises appeared randomly and repeated in five cycles. Tinnitus match and residual inhibition were performed in the tinnitus group. The data analyses were conducted using the NIRS_SPM toolbox. The group analysis results showed that the narrow-band noise caused a marginally significant decrease in HbO signal in the Brodmann 21 region (BA21), while white noise caused a significant increase in HbO signal in BA21. Notched sound did not cause significant changes in the HbO signal in the temporal cortex. And none of the three masking noises caused significant changes in the HbR signal in the temporal cortex. The depth of residual inhibition induced by the narrow-band noise and white noise significantly correlated with ΔHbO in the region of interest (ROI). However, neither the depth nor duration of the residual inhibition induced by notched sound correlated with the ΔHbO. Thus, NIRS showed three cortical activation patterns induced by three different masking noises, and correlations between residual inhibition effects and change of HbO amplitude were found. NIRS could therefore be applied in objective assessment of acoustic therapy.

[Liver safety of biosimilar of recombinant tumor necrosis factor-α receptor-antibody fusion protein in Spondyloarthritis patients under different status of HBV infection: a prospective observational study].

OBJECTIVE: To investigate the influence of recombinant human tumor necrosis factor α receptor-antibody fusion protein (rhTNFR: Fc) to the Hepatitis B virus (HBV) infection status and liver function of Spondyloarthritis (SpA) patients under different HBV infection status. METHODS: Active SpA patients with normal liver function were enrolled in Sun Yat-sen Memorial hospital from February 2012 to August 2014. All were treated with rhTNFR: Fc based therapy (monotherapy or combined therapy) for at least 12 weeks. SpA disease activity, HBV infection status and liver function were evaluated at each interview (baseline, 4(th) and 12(th) week, as primary endpoint). Part of the patients were evaluated at 24(th) week with or without extended rhTNFR: Fc treatment(as secondary endpoint) based on their choice. RESULTS: Eighty-one patients who completed 12-week follow-up visit were divided into chronic HBV carrier group (n=21), past HBV exposure group (n=25) and free of HBV infection group (n=35). Alanine transaminase (ALT) elevated (no more than 3-fold of normal) in 3 patients from 3 groups respectively at 4th week. During 24-week follow-up, none in past HBV exposure group or in free of HBV infection group developed HBV reactivation or HBV infection; and 4 patients in chronic HBV carrier group developed HBV reactivation without more than 2-fold of normalelevation of ALT. Among 7 patients with negative baseline HBV-DNA and without antiviral prophylaxis, 2 patients developed HBV reactivation at 10(th) 24(th) week of rhTNFR: Fc therapy respectively and 1 patient developed reactivation at 16(th) week (12-week rhTNFR: Fc+ thalidomide therapy and following 4-week thalidomide monotherapy), whose HBV-DNA load returned to normal spontaneously or after antiviral therapy. Four chronic HBV carriers with low-load of baseline HBV-DNA did not develop reactivation. One of 9 chronic HBV carriers with high-load of baseline HBV-DNA developed reactivation due to resistance of antiviral prophylaxis. CONCLUSIONS: Short-term rhTNFR: Fc based therapy may induce mild and transient HBV reactivation, usually without hepatitis.