Relationships between bilateral auditory brainstem activity and inter-implant interval in children with cochlear implants.

PURPOSE: To investigate the effect of the interval between bilateral cochlear implantation on the development of bilateral peripheral auditory pathways as revealed by the electrically evoked auditory brainstem response (EABR). METHODS: Fifty-eight children with profound bilateral sensorineural hearing loss were recruited. Among them, 33 children received sequential bilateral cochlear implants (CIs), and 25 children received simultaneous bilateral CIs. The bilateral EABRs evoked by electrical stimulation from the CI electrode were recorded on the day of second-side CI activation. RESULTS: The latencies of wave III (eIII) and wave V (eV) were significantly shorter on the first CI side than on the second CI side in children with sequential bilateral CIs but were similar between the two sides in children with simultaneous bilateral CIs. Furthermore, the latencies were prolonged from apical to basal channels along the cochlea in the two groups. In children with sequential CIs, the inter-implant interval was negatively correlated with the eV latency on the first CI side and was positively correlated with bilateral differences in the eIII and eV latencies. CONCLUSIONS: Unilateral CI use promotes the maturation of ipsilateral auditory conduction function. However, a longer inter-implant interval results in more unbalanced development of bilateral auditory brainstem pathways. Bilateral cochlear implantation with no or a short interval is recommended.

Electrically evoked auditory brainstem responses in deaf patients with Mondini malformation during cochlear implantation.

PURPOSE: To investigate the auditory pathway functions in deaf patients with Mondini malformation using the electrically evoked auditory brainstem response (EABR) during cochlear implantation (CI). METHODS: A total of 58 patients with severe to profound sensorineural hearing loss (SNHL) were included in this study. Of these patients, 27 cases had Mondini malformation and 31 control cases had no inner ear malformations (IEMs). Intraoperative EABRs evoked by electrical stimulation at the round window niche (RWN) and round window membrane (RWM) were recorded. RESULTS: Patients with Mondini malformation showed significantly lower EABR extraction rates than those with no IEMs did. However, for patients who showed EABRs, no significant difference in EABR thresholds, wave III (eIII) latencies, wave V (eV) latencies or eIII-eV latency intervals was found between two groups. CONCLUSION: The physiological functions of the peripheral auditory system in patients with Mondini malformation may divide into opposite extremes, as revealed by a robust EABR and the absence of the EABR, respectively. The auditory conduction function should be objectively and individually evaluated for patients with Mondini malformation by the EABR.

Thalidomide corrects impaired mesenchymal stem cell function in inducing tolerogenic DCs in patients with immune thrombocytopenia.

Thalidomide (THD) is an immunomodulatory agent used to treat immune-mediated diseases. Immune thrombocytopenia (ITP) is an autoimmune disorder in which impaired mesenchymal stem cells (MSCs) are potentially involved. We demonstrated that MSCs in ITP patients had reduced proliferative capacity and lost their immunosuppressive function, which could be corrected with THD treatment. According to the gene profile, the downregulation of caspase-8 and caspase-10, and upregulation of oct3/4 and tgf-ß1, may be associated with THD modulation. Dendritic cells (DCs) played an important role in mediating the inhibitory activity of MSCs. To study the functional alteration of DCs elicited by MSCs, we sorted DCs after incubation with MSCs and performed T-lymphocyte reaction assays. The THD-modulated MSCs from ITP patients induced mature DCs to become tolerogenic DCs, whereas unmodulated MSCs had no effect. The induction of tolerogenicity in DCs by MSCs was dependent on the expression of TIEG1 in DCs. The study reveals the inability of MSCs from ITP patients to induce tolerogenic ability in DCs. THD could restore the regulatory effect of MSCs on DCs. These findings will help us understand the pathogenesis of ITP, and with appropriate safeguards, THD may benefit patients with ITP.

Cochlear implantation with round window insertion in children with otitis media with effusion.

AIMS: To discuss indications and surgical techniques for cochlear implantation (CI) in children with profound sensorineural hearing loss and otitis media with effusion (OME). METHODS: Between January 2003 and May 2013, a total of 550 patients received cochlear implants at the Anhui Provincial Hospital, Hefei, China. Of these, 30 children with OME underwent CI with round window insertion in one stage. RESULTS: One-stage operations of CI with round window insertion were carried out in 30 children with OME. All electrodes were implanted successfully. CI was performed without complications and the electrode arrays were protected well. All implant devices worked normally and all patients performed well during an average follow-up period of 12 months. None of the patients experienced any immediate or delayed postoperative infection-related complications. CONCLUSIONS: CI with round window insertion could be safely and effectively performed in one stage in children with profound sensorineural hearing loss and OME. It is unnecessary to delay implantation to control OME, but it remains a challenging problem in operation.

Electrically Evoked Auditory Brainstem Responses in Children Fitted with Hearing Aids Prior to Cochlear Implantation.

This study investigates the effect of hearing aid use on the peripheral auditory pathways in children with sensorineural hearing loss prior to cochlear implantation, as revealed by the electrically evoked auditory brainstem response (EABR). Forty children with hearing aids were recruited. Half of them had normal inner ear structures and the other half had inner ear malformations (IEMs). The EABR was evoked by electrically stimulating the round window niche (RWN) and round window membrane (RWM) during the cochlear implantation operation. The onset age of hearing aid use was significantly correlated with the peak latencies, but not amplitudes, of the wave III (eIII) and wave V (eV). Higher EABR thresholds were found for RWN stimulation than for RWM stimulation and in the children with IEMs than in those without IEMs. Our study provides neurophysiological evidence that earlier use of hearing aids may ameliorate physiological functions of the peripheral auditory pathway in children with and without IEMs. The EABR evoked by the electrical stimulation at RWM is more sensitive compared with that at RWN for evaluating functions of the auditory conduction pathway.

Diagnostic value of 18F-FDG PET/CT versus contrast-enhanced MRI for venous tumour thrombus and venous bland thrombus in renal cell carcinoma.

The purpose of this study was to compare the ability of 18F-FDG PET/CT and contrast-enhanced MRI (CEMRI) to detect and grade venous tumour thrombus (VTT) and venous bland thrombus (VBT) in RCC and assess invasion of the venous wall by VTT. The PET/CT and CEMRI data of 41 patients with RCC were retrieved. The difference in maximum standardized uptake value (SUVmax) between VTT and VBT was analysed. According to their pathological diagnosis, the patients were divided into those with and without venous wall invasion. The PET/CT and CEMRI features, including the SUVmax of the primary lesion and VTT, maximum venous diameter, complete occlusion of the vein by VTT, and VTT morphology, were compared between the two groups. All 41 patients had VTT, and eleven of the 41 patients had VBT. The mean SUVmax of the VTT (6.33 ± 4. 68, n = 41) was significantly higher than that of the VBT (1.37 ± 0.26, n = 11; P < 0.001). Ten of the 11 cases of VBT were correctly diagnosed by 18F-FDG PET/CT, and all 11 were diagnosed by CEMRI. Both 18F-FDG PET/CT and CEMRI can effectively detect VTT and distinguish VTT from VBT. 18F-FDG PET/CT is less effective in grading VTT than CEMRI. Complete venous occlusion by VTT indicates venous wall invasion.

Recent Developments of Flavonoids with Various Activities.

Flavonoids, a series of compounds with a C6-C3-C6 structure, mostly originate from plant metabolism. Flavonoids have shown beneficial effects on many aspects of human physiology and health. Recently, many flavonoids with various activities have been discovered, which has led to more and more studies focusing on their physiological and pharmacodynamic activities. The anticancer and anti-viral activities especially have gained the attention of many researchers. Therefore, the discovery and development of flavonoids as anti-disease drugs has great potential and may make a significant contribution to fighting diseases. This review focus on the discovery and development of flavonoids in medicinal chemistry in recent years.

Brain Functional Mechanisms Determining the Efficacy of Transcutaneous Auricular Vagus Nerve Stimulation in Primary Insomnia.

Transcutaneous auricular vagus nerve stimulation (taVNS) has been reported to be effective in the treatment of primary insomnia (PI); however, its efficacy varies considerably across individuals for reasons that are unclear. In order to clarify the underlying mechanisms, this study investigated the effects of taVNS on spontaneous neuronal activity and autonomic nervous system function by functional magnetic resonance imaging (fMRI) and measurement of heart rate variability (HRV), respectively, in patients with PI. Forty patients with PI were divided into effective (group A) and ineffective (group B) groups based on their response to taVNS as determined by Pittsburgh Sleep Quality Index score reduction rate (group A ≥ 25% and group B < 25%). Spontaneous neuronal activity was measured by fractional amplitude of low-frequency fluctuations (fALFF) and HRV values and was compared between the two groups as well as before vs after taVNS. We then analyzed the correlations among efficacy of taVNS for 4 weeks, the fALFF and HRV values during continuous taVNS state. The results showed that the HRV parameter values (i.e., root mean square of successive differences, percentage of adjacent NN intervals differing by >50 ms, and high frequency) of group A were higher than those of group B during continuous taVNS state. In the fMRI scan, the fALFF values of the right cerebellum, right medial superior frontal gyrus, and bilateral supplementary motor area-which belong to the sensorimotor network (SMN)-were lower in group A than in group B during continuous taVNS state. The correlation analysis revealed that the efficacy of continuous taVNS and HRV and fALFF values were interrelated. These findings demonstrate that differential regulation of the SMN by the autonomic nervous system may be responsible for inter-individual variations in the efficacy of taVNS and suggest that HRV and fALFF are potential biomarkers for predicting PI patients' response to taVNS treatment.

Auditory Sensory Gating in Children With Cochlear Implants: A P50-N100-P200 Study.

Background: While a cochlear implant (CI) can restore access to audibility in deaf children, implanted children may still have difficulty in concentrating. Previous studies have revealed a close relationship between sensory gating and attention. However, whether CI children have deficient auditory sensory gating remains unclear. Methods: To address this issue, we measured the event-related potentials (ERPs), including P50, N100, and P200, evoked by paired tone bursts (S1 and S2) in CI children and normal-hearing (NH) controls. Suppressed amplitudes for S2 compared with S1 in these three ERPs reflected sensory gating during early and later phases, respectively. A Swanson, Nolan, and Pelham IV (SNAP-IV) scale was performed to assess the attentional performance. Results: Significant amplitude differences between S1 and S2 in N100 and P200 were observed in both NH and CI children, indicating the presence of sensory gating in the two groups. However, the P50 suppression was only found in NH children and not in CI children. Furthermore, the duration of deafness was significantly positively correlated with the score of inattention in CI children. Conclusion: Auditory sensory gating can develop but is deficient during the early phase in CI children. Long-term auditory deprivation has a negative effect on sensory gating and attentional performance.

Deficit of long-term memory traces for words in children with cochlear implants.

OBJECTIVE: Language experience can develop long-term memory traces for speech units in the brain, to ensure efficient processing of speech sounds. However, prelingually deafened children lack sufficient auditory input before cochlear implantation. Whether the experience-dependent long-term memory traces exist in prelingually deafened children with cochlear implants (CIs) remains unclear. METHODS: We presented CI and normal hearing (NH) children with Mandarin Chinese spoken disyllables in an oddball paradigm and recorded event-related potentials. Each disyllable was defined as a meaningful word or a meaningless pseudoword by the tonal information in the second syllable. RESULTS: The amplitude of mismatch negativity (MMN) elicited by words was larger than that elicited by pseudowords in NH children. However, this enhancement of the MMN amplitude was not found in CI children. Behavioral results showed later recognition points for words and lower accuracies for speech comprehension in CI children than in NH children. Furthermore, increased theta power for words compared with pseudowords was only found in NH children. CONCLUSIONS: Our findings indicate a deficit of long-term memory traces for words in prelingually deafened children with cochlear implants. SIGNIFICANCE: Early speech input may be crucial to the formation of long-term memory traces for speech units.

Molecular analysis of the gene encoding a cold-adapted halophilic subtilase from deep-sea psychrotolerant bacterium Pseudoalteromonas sp. SM9913: cloning, expression, characterization and function analysis of the C-terminal PPC domains.

Only a few cold-adapted halophilic proteases have been reported. Here, the gene mcp03 encoding a cold-adapted halophilic protease MCP-03 was cloned from deep-sea psychrotolerant bacterium Pseudoalteromonas sp. SM9913, which contains a 2,130-bp ORF encoding a novel subtilase precursor. The recombinant MCP-03, expressed in Escherichia coli BL21 and purified from fermented broth, is a multi-domain protein with a catalytic domain and two PPC domains. Compared to mesophilic subtilisin Carlsberg, MCP-03 had characteristics of a typical cold-adapted enzyme (e.g., higher activity at low temperatures, lower optimum temperature and higher thermolability). MCP-03 also exhibited good halophilic ability with maximal activity at 3 M NaCl/KCl and good stability in 3 M NaCl. Deletion mutagenesis showed that the C-terminal PPC domains were unnecessary for enzyme secretion but had an inhibitory effect on MCP-03 catalytic efficiency and were essential for keeping MCP-03 thermostable.

Cochlear implantation in Mondini's deformity: could the straight electrode array with length of 31 mm be fully inserted?

CONCLUSIONS: The straight electrode array with length of 31 mm can be fully inserted using round window insertion in cochlear implantation with Mondini's deformity. It is a safe and effective process, but also a challenging task of the full implantation in children with Mondini's deformity. OBJECTIVE: The aim of this study is to discuss whether the straight electrode array with a length of 31 mm could be fully inserted in cochlear implantation with Mondini's deformity. METHODS: A chart review of 30 patients undergoing cochlear implantation with Mondini's deformity using the electrode array with length of 31 mm was undertaken from January 2012 and December 2015 in Anhui Provincial Hospital. RESULTS: Full insertion of the straight electrode array with length of 31 mm were performed successfully in all patients with Mondini's deformity using round window insertion. Resistance was not encountered while introducing the electrodes. Ten of 30 patients had cerebrospinal fluid drainage during cochlear implantation. Cerebrospinal fluid drainage was controlled with small pieces of temporalis fascia packing round window in all patients. Intra-operative neural response telemetry was performed in all patients, and results were good. The result of X-ray showed proper placement of the cochlear implant electrode array. During surgery, no patients had experienced any immediate or delayed post-operative complications such as wound infection, intracranial complication, extrusion, or migration of the implant during an average follow-up period of 6-36 months.

The roles of vitamin B12 and vitamin D in children with intractable epilepsy.

Epilepsy is a chronic neurological disorder. Antiepileptic drugs (AEDs) can cause vitamin B12 or D deficiency in children with intractable epilepsy. In this study, we measured salivary superoxide dismutase (SOD) and metalloproteinsases (MMP) levels in the patients with vitamin B12 and vitamin D treatment. Cytokines and chemokines were measured using ELISA. The mean salivary value of SOD activity in the control group was 1.75 ± 0.21 U/ml. In the treatment group, the value was 1.33 ± 0.18 U/ml. The salivary MMP 2, MMP 3, and MMP 9 levels of the patients with vitamin D and vitamin B12 treatment were lower than that in the patients without vitamin D and vitamin B12 treatment. Interleukin 1ß (IL-1ß), IL-6, IL-8, macrophage inflammatory protein 1ß (MIP-1ß), monocyte chemoattractant protein-1 (MCP-1) and IFN-inducible protein 10 (IP-10) were significantly decreased in the cortex of our patients with vitamin D and vitamin B12 treatment. In this study, a clear association between vitamin D and vitamin B12 treatment and epilepsy was identified. We now plan to investigate the genetic factors that underlie vitamin D and vitamin B12 treatment in patients treated with AEDs.

Using autogenous mastoid cortical bone cap to cover the mastoidectomy defect during cochlear implantation.

OBJECTIVES: Assessment of autogenous mastoid cortical bone cap to cover the mastoidectomy defect via transmastoid and posterior tympanotomy approach surgical technique during cochlear implantation. METHODS: A chart review of the autogenous mastoid cortical bone cap to cover the mastoidectomy defect via transmastoid and posterior tympanotomy approach surgical technique in 540 patients undergoing cochlear implantation was undertaken from January 2010 and December 2013 in Anhui Provincial Hospital. RESULTS: The mastoidectomy defect was reconstructed using autogenous cortical bone cap in all cochlear implantation patients. No depression was found in the postauricular site. None of the patients had experienced any immediate or delayed postoperative infection complication such as wound infection, post-auricular abscess or intracranial complication. CONCLUSIONS: The technique of autogenous mastoid cortical bone cap to cover the mastoidectomy defect is a good option during cochlear implantation via transmastoid and posterior tympanotomy approach. It can prevents depression of the postauricular site, and also may be able to prevent infection of the wound and the implanted processor. Autogenous cortical bone cap is easy to handle, ready available, stable, resorption resisting, also cost-saving in cochlear implantation surgery.

Cochlear implantation with round window insertion in children less than 2 years.

CONCLUSIONS: Cochlear implantation (CI) with round window insertion could be performed safely and effectively in children less than 2 years old, but it is a more challenging operation. OBJECTIVE: To discuss the key surgical techniques of CI in children less than 2 years old with profound sensorineural hearing loss. METHODS: This was a retrospective study of data collected from patients undergoing CI. CI was performed with round window insertion in children less than 2 years old in Anhui Provincial Hospital between January 2003 and May 2013. RESULTS: CI was performed in a total of 85 children. Of these, 80 children (90%) had round window insertion. All children had full insertions of the electrode array, in which the CI went normally and the electrode array was protected well. All implant devices worked normally and all patients performed well during an average follow-up period of 6-36 months. No major or minor complications occurred, and there was no perioperative anesthetic complication.

Electrode array misplacement into the superior semicircular canal: as a rare complication of cochlear implantation.

OBJECTIVE: To report electrode array misplacement into the superior semicircular canal occurring as an rare complication of cochlear implantation through round window insertion, and to explore the causative association between electrode array misplacement and cochlear implantation surgical techniques. METHODS: A chart review of the electrode array misplacement into the superior semicircular canal and their management in 695 patients undergoing cochlear implantation was undertaken from January 2003 and January 2014 in Anhui Provincial Hospital. RESULTS: There were two children of electrode array misplacement into the superior semicircular canal complication, and the rate was 0.28%. CONCLUSIONS: Electrode array misplacement into the superior semicircular canal associated with cochlear implantation is rare. Surgeons should be aware of that the smaller round window maybe the reason of electrode array misplacement through round window insertion. Intra-operative neural response telemetry and X-ray can alert the surgeon the problem with the array's misplacement, which can be identified by postoperative CT.

[Weighted estimation methods for multistage sampling survey data].

Multistage sampling techniques are widely applied in the cross-sectional study of epidemiology, while methods based on independent assumption are still used to analyze such complex survey data. This paper aims to introduce the application of weighted estimation methods for the complex survey data. A brief overview of basic theory is described, and then a practical analysis is illustrated to apply to the weighted estimation algorithm in a stratified two-stage clustered sampling data. For multistage sampling survey data, weighted estimation method can be used to obtain unbiased point estimation and more reasonable variance estimation, and so make proper statistical inference by correcting the clustering, stratification and unequal probability effects.