Preimplantation genetic testing for hereditary hearing loss in Chinese population.

PURPOSE: To evaluate the clinical validity of preimplantation genetic testing (PGT) to prevent hereditary hearing loss (HL) in Chinese population. METHODS: A PGT procedure combining multiple annealing and looping-based amplification cycles (MALBAC) and single-nucleotide polymorphisms (SNPs) linkage analyses with a single low-depth next-generation sequencing run was implemented. Forty-three couples carried pathogenic variants in autosomal recessive non-syndromic HL genes, GJB2 and SLC26A4, and four couples carried pathogenic variants in rare HL genes: KCNQ4, PTPN11, PAX3, and USH2A were enrolled. RESULTS: Fifty-four in vitro fertilization (IVF) cycles were implemented, 340 blastocysts were cultured, and 303 (89.1%) of these received a definite diagnosis of a disease-causing variant testing, linkage analysis and chromosome screening. A clinical pregnancy of 38 implanted was achieved, and 34 babies were born with normal hearing. The live birth rate was 61.1%. CONCLUSIONS AND RELEVANCE: In both the HL population and in hearing individuals at risk of giving birth to offspring with HL in China, there is a practical need for PGT. The whole genome amplification combined with NGS can simplify the PGT process, and the efficiency of PGT process can be improved by establishing a universal SNP bank of common disease-causing gene in particular regions and nationalities. This PGT procedure was demonstrated to be effective and lead to satisfactory clinical outcomes.

Bilateral EABR stimulating mode testing bilateral CI patients refecting binaural integration:a preliminary study.

OBJECTIVE: To analyze binaural integration, we used a new stimulation mode of the electrically evoked auditory brainstem response (EABR), to reflect bilaterally implanted cochlear function. DESIGN: EABR was tested using the following procedure: First, both ears were evaluated separately, with the contralateral speech processor closed (C), followed by another measurement with both processors open (O). Subsequently, the eV latencies and amplitudes were assessed. The Speech, Spatial, and Qualities of Hearing Scale (SSQ), Categories of auditory performance (CAP) and speech intelligibility rating (SIR) scores were used to assess binaural hearing ability subjectively. STUDY SAMPLE: Fifteen subjects with bilateral CI from 1997 to 2018 were recruited, each diagnosed with severe to profound hearing loss. RESULTS: All SSQ scores, except for one, were greater than six (the exception scored 1.3/0.8/1.0). All CAP/SIR scores except one were greater than 6/4 (the exception scored 0/1). All patients exhibited good quality EABR measurements. The open contralateral processor significantly reduced the eV latency while enhancing the eV amplitude compared to monaural stimulation. The objective EABR results were consistent with subjective speech perception and auditory ability assessed using the SSQ scale. CONCLUSION: The EABR accurately reflected auditory pathway maturation and development after CI; thus, reflecting accordance with subjective speech and hearing performances. Furthermore, bilateral CI facilitates binaural integration and auditory brainstem plasticity.

Gene4HL: An Integrated Genetic Database for Hearing Loss.

Hearing loss (HL) is one of the most common disabilities in the world. In industrialized countries, HL occurs in 1-2/1,000 newborns, and approximately 60% of HL is caused by genetic factors. Next generation sequencing (NGS) has been widely used to identify many candidate genes and variants in patients with HL, but the data are scattered in multitudinous studies. It is a challenge for scientists, clinicians, and biologists to easily obtain and analyze HL genes and variant data from these studies. Thus, we developed a one-stop database of HL-related genes and variants, Gene4HL (http://www.genemed.tech/gene4hl/), making it easy to catalog, search, browse and analyze the genetic data. Gene4HL integrates the detailed genetic and clinical data of 326 HL-related genes from 1,608 published studies, along with 62 popular genetic data sources to provide comprehensive knowledge of candidate genes and variants associated with HL. Additionally, Gene4HL supports the users to analyze their own genetic engineering network data, performs comprehensive annotation, and prioritizes candidate genes and variations using custom parameters. Thus, Gene4HL can help users explain the function of HL genes and the clinical significance of variants by correlating the genotypes and phenotypes in humans.

Management of delayed-onset skin flap complications after pediatric cochlear implantation.

PURPOSE: To review delayed-onset skin flap complications associated with pediatric cochlear implantation (CI) in our institute, analyze the etiology, and explore effective treatment strategies. METHODS: Retrospective analyses of 811 children who had undergone cochlear implantation between January 2003 and March 2019 were performed. Twelve (1.48%) patients developed skin flap complications after CI. We present a classification of flap issues and wound histopathology following cochlear implantation. The interventions for flap problems included drug treatment, aspiration, local wound care, revision surgery, and explantation depending on the clinical situation. The temporalis myofascial reconstructive option is discussed. RESULTS: Seven subjects were cured with conservative treatment. Five cases with flap infection or necrosis underwent revision surgery, with wound closure in three cases (60%) and revision surgery with explantation in the remaining two cases (40%). Explantation ultimately led to wound healing in all cases. They all achieved excellent performance through re-implantation. CONCLUSION: Flap complications after CI are rare but treatable. Comprehensive treatments should be developed to achieve a stable and healed wound for CI.

Predictive values of maximum changes of brainstem auditory evoked potentials during microvascular decompression for hemifacial spasm.

BACKGROUND: Brainstem auditory evoked potentials (BAEPs) have been widely monitored to prevent hearing loss (HL) during microvascular decompression (MVD) for hemifacial spasm (HFS); however, their predictive value is still unclear. The aim of this study is to investigate the predictive values of the maximum changes in BAEPs and define the best warning indicator and a cutoff value (CV) during HFS-MVD. METHODS: The clinical data of 93 HFS-MVD patients were retrospectively analysed. The maximum change rates of the latency and amplitude of waves I, III, and V and the interpeak latencies (IPLs) I-III, I-V, and III-V, when BAEPs change most during MVD, were defined. Pure tone audiometry was performed to evaluate hearing loss (HL). Logistic regression, propensity score, receiver operating curve (ROC), and area under the curve (AUC) were used to identify the predictive value of relevant indexes and to determine the CV (with the largest Youden index) of the best index at different levels of HL. RESULTS: The AUCs of BAEPs for predicting HL were 0.98, 0.92, and 0.84 for 50 dB, 30 dB, and 10 dB, respectively. The amplitude of wave V (AwV) was the best single predictive index at all three HL levels. The CV of AwV was 55% (50 dB), 46% (30 dB), and 34% (10 dB). At 50 dB HL, the predictive value of IPLs I-V (AUC 0.89 with CV 0.6 ms) was better than that of LwV (AUC 0.82 with CV 1 ms). CONCLUSION: BAEPs can predict HL well. AwV is the best single predictive index of all BAEPs. The reduction of AwV by 34% (watching), 46% (reporting), and 55% (warning) can be used as a sliding-scale warning sign. In addition, IPLs I-V (> 0.6 ms) and LwV (> 1 ms) should also be observed and reported during MVD.

Crystallization of highly supercooled glass-forming alloys induced by anomalous surface wetting.

Crystallization in highly supercooled Cu50Zr50 films close to the glass transition is studied by using molecular dynamics simulations. Spontaneous nucleation is observed at the simulation timescale in contrast to the bulk counterpart. We find that nucleation occurs at free surfaces owing to the partial wetting of the nucleus by melt. The anomalous wetting phenomenon is closely related to strong density layering arising from the surface: the high density associated with surface layering increases surface energy of supercooled melts, resulting in that one facet of the crystalline embryo is preferentially formed on the film surface. The surface-based embryo is then developed into a stable nucleus by bridging two surfaces of thin films. The kinetics and thermodynamics analyses based on the mean first-passage time method show that the nucleation process still follows the description of the classical nucleation theory despite extremely high supercoolings. In nucleating, the slow interface dynamics becomes dominant and induces a low nucleation rate although the nucleation barrier is very low. The subsequent crystal growth is found to proceed in a quasi-two-dimensional manner with a ramified interface morphology, which is analogous to percolative crystals predicted in glass-forming liquids.

The development of hearing in prelingually deaf children with white matter changes in the first year after cochlear implantation.

Background: The development of hearing and plasticity of brain after cochlear implantation (CI) for prelingually deaf children with white matter changes (group A) is unclear.Objective: To investigate the development of hearing for children in group A during 1 year after CI activation, compared with non-complicated peers (group B).Materials and methods: Twenty-one and 22 children (average age is about 5 years old) were included in groups A and B, respectively. Questionnaires were used to assess the hearing ability at pre-CI, 1, 6 and 12 months after CI activation (called Mpre, M1, M6, M12 for short). In addition, MMRs to pure tones were investigated at the same three time points after CI.Results: There is no significant difference in scores on questionnaires, MMR incidence, latency or amplitude between children in two groups. Scores on questionnaires showed a significant progressive improvement in two groups during the first year after CI. Furthermore, MMR incidence at M6 was significantly higher than that at M1, and MMR latency at M12 was significantly shorter than that at M1.Conclusions and significance: Prelingually deaf children with white matter changes achieved rapid development and comparable outcomes with CI peers over the first year after CI.

One-dimensional water nanowires induced by electric fields.

Self-aggregation of water vapour molecules under external electric fields is systemically investigated by using molecular dynamics simulations. It is found that small water clusters aggregate into one-dimensional water nanowires along the electric field direction. The electric field strength plays a crucial role in tuning the nanowire structure. Under relatively weak electric fields such as E = 0.1 V Å-1, square and pentagonal prism-like structures are preferred; when intermediate strength electric fields are applied (E = 1.0 V Å-1), water nanowires featuring a disordered mixture of four-, five- and six-membered rings are formed; and an open ordered structure which is reminiscent of two-dimensional (2D) ice is observed when the field strength becomes very high (E > 3.0 V Å-1). Bond parameter analysis based on density-functional theory calculations shows that the electric field affects anisotropically the conformation of water molecules as well as the hydrogen-bond properties. Along the electric field, the H-O bond is stretched and the hydrogen bond shrinks with field strength in contrast to the changes perpendicular to the electric field. As a result, the hydrogen bonding is enhanced along the electric field. Under very high electric fields, the anisotropic hydrogen-bond network opens up via breaking of the bonds perpendicular to the electric field and ultimately relaxes into a loose quasi-2D ordered network.

Density-wave-modulated crystallization in nanoscale silicon films and droplets.

Free surfaces have been known to significantly influence the crystallization of tetrahedral liquids. However, a comprehensive understanding of the influence mechanism is still lacking at present. By employing molecular dynamics simulations, we find that the nucleation probability in nanoscale silicon films and droplets exhibits a ripple-like distribution spatially. This phenomenon is closely related to the structural order wave, which is induced by the density fluctuations arisen from the volume expansion in a confinement environment defined by free surfaces. By the aid of the intrinsic relation between the tetrahedral order and the density, the analytic results based on the density wave equation well account for the nucleation probability distributions in both films and droplets. Our findings reveal the underlying mechanism of the surface-assisted nucleation in tetrahedral liquids and provide an overall description of crystallization in liquid films and droplets.

[Immediate recurrent laryngeal nerve reconstruction in the treatment of thyroid cancer invading the recurrent laryngeal nerve].

OBJECTIVE: To explore the application of immediate recurrent laryngeal nerve reconstruction in the treatment of thyroid cancer invading the recurrent laryngeal nerve. METHODS: Ten patients with thyroid cancer invading unilateral recurrent laryngeal nerve underwent radical surgery and immediate recurrent laryngeal nerve reconstruction. The reconstructive surgical approach included recurrent laryngeal nerve decompression surgery, end-to-end anastomosis of the recurrent laryngeal nerve, anastomosis of ansa cervicalis nerve to the recurrent laryngeal nerve, and nerve-muscle pedicle (NMP) technique. Among the ten patients, one underwent nerve decompression, one underwent end-to-end anastomosis of the recurrent laryngeal nerve, seven had anastomosis of ansa cervicalis to recurrent laryngeal nerve, and one case had anastomosis of ansa cervicalis to recurrent laryngeal nerve combined with nerve-muscle pedicle (NMP) technique. The effect of surgery was evaluated by videolaryngoscopy, maximum phonation time (MPT), phonation efficiency index (PEI) and voice assessment. T-test was used in the statistical analysis. RESULTS: All of the 10 patients had no complications including tumor recurrence and hypoparathyroidism after the surgery. Their hoarseness symptoms were improved, and the patients returned to normal or near-normal voice. Postoperative videolaryngoscopy showed that paralyzed vocal cord returned to normal muscle tone and volume, and the vocal cord vibration and mucosal wave were symmetric and the patients got good glottal closure. The pre- and post-operative maximum phone times of the patients were (4.52 ± 0.89) s and (11.91 ± 1.87) s, respectively (P < 0.01). The pre- and post-operative phonation efficiency indices were (1.37 ± 0.43) s/L and (4.02 ± 1.33) s/L, respectively (P < 0.05). CONCLUSIONS: In patients with thyroid cancer invading unilateral recurrent laryngeal nerve, immediate recurrent laryngeal nerve reconstruction following radical surgery of thyroid cancer can effectively achieve recovery in phonation function and improve the quality of life of the patients.

[Presentation and management of allergic fungal rhinosinusitis].

OBJECTIVE: To assess the presentation of allergic fungal rhinosinusitis (AFRS) and describe the line of management in our setup. METHOD: Twenty-six cases of AFRS from October 2002 to June 2006 were retrospectively analyzed for the study in Department of Otorhinolaryngology Head and Neck Surgery, Peking University First Hospital. Laboratory findings (especially total serum IgE level and special serum IgE level) and computed tomography were noted preoperation. Surgical specimens were sent for mycology and histopathologic analysis. The management included endoscopic sinus debridement, adequate sinus aeration, pre- and post-operative use of steroids and saline irrigations with antifungal drugs. RESULT: Nasal obstruction and hyposmia were the commonest presentations. In 21 (80.8%) of 26 patients, AFRS was fund to be associated with allergic diseases. CT scan showed serpiginous or patchy increased attenuation within the completely opacified sinuses on reconstructed soft tissue window. Some of the involved sinuses had bone erosion and expansion. 84.6% (22/26) patients had elevated total IgE levels, 76.9% (20/26) had positive for sIgE levels to fungal allergen. Fungal smear were positive for all 26 patients. But only 14 surgical specimens were positive for fungal cultures. The most common causative agent was Aspergillus. The involved mucosa and allergic mucin with H & E staining contained clusters or sheets of degenerating eosinophils. Charcot-Leyden crystals was found in 8 surgical specimens. The follow-up after a year, the mucosa recovered epithelization in 19 patients. CONCLUSION: The diagnosis of AFRS required to depend on history, CT scanning, histopathology, mycologic and immunologic monitoring. Comprehensive treatment with endoscopic sinus surgery, steroids and saline irrigations with antifungal drugs is effective method.