Reading comprehension skill in English as a second language of Japanese middle school students with cochlear implants.

OBJECTIVES: To assess the English reading comprehension skill of Japanese middle school students with cochlear implants (CIs). MATERIALS AND METHODS: The subjects were pre- or perilingually deafened CI recipients between seventh and ninth grades (age 12-15 years). English reading comprehension skill was evaluated using the Norm Referenced Test developed for Japanese students. Furthermore, factors related to English reading comprehension were assessed, focusing on a total of 11 variables: age; sex; age at CI; length of CI use; aided pure-tone thresholds with CI; Japanese listening word recognition score; performance intelligence quotient (PIQ) score; verbal intelligence quotient (VIQ); grade; school type; and Japanese reading comprehension skill. RESULTS: A total of 40 subjects completed the test. Their average word recognition score was good, at 80.2%,and the average age at CI was late, at 4.4 years. The chi-square goodness of fit test showed the English reading comprehension skill level deviated toward lower achievement in the students with CIs compared with children with normal-hearing. VIQ and Japanese reading comprehension skill were correlated with English reading skill. On the other hand, there was no relationship between English reading skill and the factors of hearing level and CI experience.

The actual state of and factors for speech perception ability in adult cochlear implant wearers.

PURPOSE: To elucidate the status of speech perception ability in cochlear implant wearers with unknown deafness causes. MATERIALS AND METHODS: We extracted 1095 patients between January 1, 1986, and December 31, 2019; among them, there were 418 first-surgery adults who wore implants made by Cochlear. Finally, we included 204 patients (69 males and 135 women) without cochlear morphological abnormalities. All electrodes were inserted into the cochlea, without major intraoperative and postoperative problems. The minimum, maximum, and average ages of surgery were 17 years, 85 years, and 56.5 years, respectively. The participants were divided according to the electrode (Group A, CI22 straight electrode; Group B, CI24 straight electrode; Group C, modiolar hugging electrode type electrode; and Group D, slim straight electrode). We evaluated the following parameters: cochlear implant threshold and single-syllable, word, and single-sentence hearing ability. Further, we investigated impactful background factors. RESULTS: There was a decreased cochlear implant threshold in Groups B and C. Group B had a better ability to hear single syllables, words, and sentences than Group A. Groups C and D had significantly better ability to hear words than Group B. Low hearing aid threshold, good hearing ability with the 67S hearing aid, and short duration of hearing loss were associated with enhanced hearing ability. CONCLUSION: In this study, it was suggested that the listening ability may have improved because of the progress of the electrodes. However, the possibility of a ceiling effect was also suggested.

Modeling gap junction beta 2 gene-related deafness with human iPSC.

There are >120 forms of non-syndromic deafness associated with identified genetic loci. In particular, mutation of the gap junction beta 2 gene (GJB2), which encodes connexin (CX)26 protein, is the most frequent cause of hereditary deafness worldwide. We previously described an induction method to develop functional CX26 gap junction-forming cells from mouse-induced pluripotent stem cells (iPSCs) and generated in vitro models for GJB2-related deafness. However, functional CX26 gap junction-forming cells derived from human iPSCs or embryonic stem cells (ESCs) have not yet been reported. In this study, we generated human iPSC-derived functional CX26 gap junction-forming cells (iCX26GJCs), which have the characteristics of cochlear supporting cells. These iCX26GJCs had gap junction plaque-like formations at cell-cell borders and co-expressed several markers that are expressed in cochlear supporting cells. Furthermore, we generated iCX26GJCs derived from iPSCs from two patients with the most common GJB2 mutation in Asia, and these cells reproduced the pathology of GJB2-related deafness. These in vitro models may be useful for establishing optimal therapies and drug screening for various mutations in GJB2-related deafness.

Modification of the transglucosylation properties of α-glucosidases from Aspergillus oryzae and Aspergillus sojae via a single critical amino acid replacement.

We constructed enzyme variants of the α-glucosidases from Aspergillus oryzae (AoryAgdS) and Aspergillus sojae (AsojAgdL) by mutating the amino acid residue at position 450. AoryAgdS_H450R acquired the ability to produce considerable amounts of α-1,6-transglucosylation products, whereas AsojAgdL_R450H changed to produce more α-1,3- and α-1,4-transglucosylation products than α-1,6-products. The 450th amino acid residue is critical for the transglucosylation of these α-glucosidases.

Cochlear implantation in a patient with a POU4F3 mutation.

Cochlear implants (CIs) are generally considered useful in the treatment of hereditary hearing loss with progressive deafness. Early CI can be beneficial for maintaining social activities in POU4F3 mutation patients.

Generation of two induced pluripotent stem cell lines from PBMCs of siblings carrying c.235delC mutation in the GJB2 gene associated with sensorineural hearing loss.

The gap junction beta-2 (GJB2) gene is the most common genetic cause of hereditary deafness worldwide. Especially, the 235delC mutation in GJB2 is most prevalent in East Asia. In this study, we generated two iPSC lines from PBMCs of siblings carrying homozygous 235delC mutation which exhibits an audiometric phenotype of profound hearing loss. These iPSC lines had normal karyotype, showed expression of pluripotency markers, and could differentiate into three germ layers. These disease specific iPSC lines may be useful for the construction of the disease models and for the elucidation of pathogenesis in GJB2-related deafness.

Analysis of Transglucosylation Products of Aspergillus niger α-Glucosidase that Catalyzes the Formation of α-1,2- and α-1,3-Linked Oligosaccharides.

According to whole-genome sequencing, Aspergillus niger produces multiple enzymes of glycoside hydrolases (GH) 31. Here we focus on a GH31 α-glucosidase, AgdB, from A. niger . AgdB has also previously been reported as being expressed in the yeast species, Pichia pastoris ; while the recombinant enzyme (rAgdB) has been shown to catalyze tranglycosylation via a complex mechanism. We constructed an expression system for A. niger AgdB using Aspergillus nidulans . To better elucidate the complicated mechanism employed by AgdB for transglucosylation, we also established a method to quantify glucosidic linkages in the transglucosylation products using 2D NMR spectroscopy. Results from the enzyme activity analysis indicated that the optimum temperature was 65 °C and optimum pH range was 6.0-7.0. Further, the NMR results showed that when maltose or maltopentaose served as the substrate, α-1,2-, α-1,3-, and small amount of α-1,1-ß-linked oligosaccharides are present throughout the transglucosylation products of AgdB. These results suggest that AgdB is an α-glucosidase that serves as a transglucosylase capable of effectively producing oligosaccharides with α-1,2-, α-1,3-glucosidic linkages.

A Novel α-Glucosidase of the Glycoside Hydrolase Family 31 from Aspergillus sojae.

We characterized an α-glucosidase belonging to the glycoside hydrolase family 31 from Aspergillus sojae. The α-glucosidase gene was cloned using the whole genome sequence of A. sojae, and the recombinant enzyme was expressed in Aspergillus nidulans. The enzyme was purified using affinity chromatography. The enzyme showed an optimum pH of 5.5 and was stable between pH 6.0 and 10.0. The optimum temperature was approximately 55 °C. The enzyme was stable up to 50 °C, but lost its activity at 70 °C. The enzyme acted on a broad range of maltooligosaccharides and isomaltooligosaccharides, soluble starch, and dextran, and released glucose from these substrates. When maltose was used as substrate, the enzyme catalyzed transglucosylation to produce oligosaccharides consisting of α-1,6-glucosidic linkages as the major products. The transglucosylation pattern with maltopentaose was also analyzed, indicating that the enzyme mainly produced oligosaccharides with molecular weights higher than that of maltopentaose and containing continuous α-1,6-glucosidic linkages. These results demonstrate that the enzyme is a novel α-glucosidase that acts on both maltooligosaccharides and isomaltooligosaccharides, and efficiently produces oligosaccharides containing continuous α-1,6-glucosidic linkages.

Bilateral Versus Unilateral Cochlear Implantation in Adult Listeners: Speech-On-Speech Masking and Multitalker Localization.

Binaural hearing helps normal-hearing listeners localize sound sources and understand speech in noise. However, it is not fully understood how far this is the case for bilateral cochlear implant (CI) users. To determine the potential benefits of bilateral over unilateral CIs, speech comprehension thresholds (SCTs) were measured in seven Japanese bilateral CI recipients using Helen test sentences (translated into Japanese) in a two-talker speech interferer presented from the front (co-located with the target speech), ipsilateral to the first-implanted ear (at +90° or -90°), and spatially symmetric at ±90°. Spatial release from masking was calculated as the difference between co-located and spatially separated SCTs. Localization was assessed in the horizontal plane by presenting either male or female speech or both simultaneously. All measurements were performed bilaterally and unilaterally (with the first implanted ear) inside a loudspeaker array. Both SCTs and spatial release from masking were improved with bilateral CIs, demonstrating mean bilateral benefits of 7.5 dB in spatially asymmetric and 3 dB in spatially symmetric speech mixture. Localization performance varied strongly between subjects but was clearly improved with bilateral over unilateral CIs with the mean localization error reduced by 27°. Surprisingly, adding a second talker had only a negligible effect on localization.

Speech recognition in bilaterally cochlear implanted adults in Tokyo, Japan.

INTRODUCTION: The clinical effects of bilateral cochlear implantation (BCI) include binaural summation and better hearing under noise conditions. This study retrospectively examined the utility of BCI compared to unilateral cochlear implantation (CI) in adults. PATIENTS AND METHODS: We investigated 34 adults who underwent BCI, comparing speech recognition between BCI and first CI under silent and noise conditions. We assessed correlations between speech recognition after first and second CIs, and between the interval from first to second CI surgery and speech recognition of second CI. RESULTS: Word recognition score (WRS) and sentence recognition score (SRS) were significantly better after BCI than after first CI under conditions of silence and noise. No significant correlation was found between speech recognition after first CI and that after second CI, or between inter-implant interval and speech recognition of second CI for either WRS or SRS. CONCLUSIONS: The utility of BCI in Japanese patients was shown. Patients have no need to be pessimistic about hearing after the second implantation even if speech recognition after the first implantation is poor. A long interval from first CI does not necessarily contraindicate contralateral implantation in adults.

Stapes fixation accompanied with abnormal facial nerve pathway.

The patient was a 52-year-old woman. She had been aware of her bilateral hearing loss since she was 20 years old. The hearing in her left ear started to deteriorate at the age of 49. Pure-tone audiometry showed a bilateral mixed hearing loss. The hearing levels for the right ear and the left ear were 52 dB and 68 dB, respectively. There were no remarkable findings in a computed tomography (CT) scan of the temporal bone. We suspected that she had otosclerosis, and an operation was performed on her left ear. When the incudostapedial joint (I-S joint) was exposed to investigate the movement of the stapes, a soft white band that ran under the superstructure of the stapes was noted. By using a nerve monitoring system, we confirmed that the white band was the bare facial nerve. The ossicular chain was normal, except for a malformed stape due to the facial nerve, and the footplate of the stapes was fixed. Therefore, she was diagnosed as having otosclerosis with an abnormal facial nerve pathway. The malformed superstructure of the stapes was removed carefully. When the ectopic facial nerve was shifted to anteroinferior side, the oval window could be seen. Stapedotomy using a Teflon piston prosthesis was performed with no complications.

[Subjective evaluation of cochlear implants through a questionnaire survey in 100 long term adult cochlear implant users].

The satisfaction level is one of the important parameters to evaluate the effectiveness of cochlear implant (CI) in adult CI users. The purpose of this study is to investigate what factor improves the satisfaction level in adult CI users. Questionnaires were used to evaluate the items concerning the satisfaction level. One hundred patients who underwent cochlear implant placement at or over the age of 20 years were enrolled in this study. All patients had an experience of at least 5 years of CI use. To evaluate the effect of CI, questionnaire items were answered about the common communicative methods, listening under various situations, points of dissatisfaction, useful level, anxiety level without CI, satisfaction level, and the duration of CI usage. Sixty two percent of the patients were satisfied with the effect of CI and 80% felt that their CI was useful. Their listening results tended to be better in quieter environments or conversation in small groups. Furthermore, listening was related to the useful and satisfaction levels. Therefore, the better they could hear, the more they were satisfied with their CI, and appreciated its usefulness. The frequency of using CI as a communicative method (application level of CI) was statistically related to useful level, but no statistical relationship was seen between the application level of CI and anxiety level or satisfaction levels. These results suggest that other factors such as psychological status might affect the satisfaction level in addition to the CI application level. We concluded that it was necessary for us to understand the listening level before CI surgery in order to predict the postoperative course and to give an appropriate explanation to the patients.

Long-term complications after cochlear implantation.

OBJECTIVE: Cochlear implantation has become an effective treatment for many profoundly deaf patients. As with any surgical procedure, a proportion of patients suffer postoperative complications. The aim of this study was to analyze long-term postoperative complications in patients with cochlear implants with a view to improve clinical interventions and propose a consensus for reporting complications. METHODS: A total of 406 cases received cochlear implants between December 1985 and April 2007 at Tokyo Medical University (TMU) Hospital. We retrospectively reviewed case notes from 366 patients who had undergone cochlear implantation (215 adults and 151 children) after excluding 40 patients of re-implantation including 13 cases implanted initially at other hospitals. Life-threatening, major and minor complications were examined retrospectively. RESULTS: Major complications occurred following cochlear implantation in 32 patients (8.7%) who had received their initial implant at TMU Hospital. Revision surgery was required for 30 patients. The mean age at implantation was 33 years 6 months (range, 1 year 9 months to 83 years; median, 37 years). The main etiology of deafness was unknown or progressive (113, 52.6%) in adults and congenital (132, 87.4%) in children. The cause of deafness was meningitis in 41 cases (11.2%), and 26 cases (7.1%) were diagnosed with idiopathic sudden deafness. Flap-related problems (including middle ear infection and/or flap necrosis) developed in 13 cases (3.6%), with 12 cases (7 adults, 5 children) requiring re-implantation. Electrode slip-out occurred in 8 patients (7 adults, 1 child). All adult cases in whom electrodes slipped out underwent implantation before 1994, while the child (1 pediatric case) was operated in 2003. All cases required re-implantation and most cochlear implantations were performed using the modified split-bridge technique after 1997. Six patients (4 adults, 2 children) experienced device failure. Four patients experienced electrode problems. Non-surgical major complications included 1 patient with permanent facial nerve paralysis as a result of thermal injury in 1995. The total number of minor medical and surgical complications was 27, representing 7.4% of all operations. CONCLUSION: Many cases of major complications, including electrode problems and facial paralysis, excluding traumatic device failure were considered avoidable by strict operative and postoperative procedures. Some cases of flap infection and traumatic device failure may not be able to be avoided completely, and every possible care should be taken by implant patients and others involved.

Cochlear implantation in a patient with Epstein syndrome.

Epstein syndrome is a rare disease which is accompanied by nephritis, sensorineural hearing impairment and macrothrombocytopenia. It has been suggested that this syndrome is a hereditary disease associated with mutations in MYH9, which encodes non-muscle myosin heavy chain IIA. We report a case of a patient with Epstein syndrome in whom bilateral profound hearing impairment developed and who had undergone cochlear implantation 9 years previously. Prior to this, the patient showed progressive sensorineural hearing impairment and had become completely deaf by the age of 25. A cochlear implant was successfully used with a speech discrimination score of 98% (sentence test). However, in the present case, peri- and postoperative complications occurred: tympanic perforation remained after a promontory stimulation test, followed by transitory otitis with purulent discharge. Therefore, tympanoplasty was performed simultaneously with cochlear implantation. These complications were considered to be caused by platelet dysfunction and delayed wound healing. Furthermore, cochlear destruction was observed 8 years postoperatively. In Epstein syndrome, the mechanism of osseous change remains uncertain. To the best of our knowledge, this is the first case report of Epstein syndrome in a patient with long-term use of a CI.

The clinical features of patients with the homozygous 235delC and the compound-heterozygous Y136X/G45E of the GJB2 mutations (Connexin 26) in cochlear implant recipients.

OBJECTIVE: This study aimed to investigate the prevalence of GJB2 gene for the 235delC mutations, the clinical features and the outcomes of patients who had undergone cochlear implantation. METHODS: We have sequenced the coding region of GJB2 gene for 135 patients with sensorineural deaf from September 2000 to May 2009. Of the 135 patients, the patients with the homozygous 235delC and the compound-heterozygous Y136X/G45E were detected and were investigated clinically. RESULTS: The GJB2 gene for the 235delC mutations was found in 39 alleles of 270 alleles (14.4%), especially for the homozygous of 235delC was detected in 26 alleles (9.6%), the single heterozygous of 235delC was 1 allele (0.4%), the compound heterozygous of 235delC was found in 12 alleles (4.4%). Of 16 subjects (29 alleles) with the homozygous 235delC and the compound-heterozygous Y136X/G45E, 2 subjects (4 alleles) were found to have complications. All of the subjects were found to show severe hearing loss and some of them have indicated progressive hearing loss. However, they showed better performance regarding the thresholds after implantation. The subjects with complications, although, suggested poorer performance in the auditory speech performance. CONCLUSION: The findings of poorer outcomes might depend on complications and brain functions. In addition, considering the blood test parameters, an independent elevated LDH and ChE at diagnosis were found to be associated with hereditary enzyme's metabolic disease. Therefore, the value of LDH measurements in patients might be a helpful predictive parameter in hereditary diseases.

Prevalence of GJB2 causing recessive profound non-syndromic deafness in Japanese children.

OBJECTIVE: GJB2 (gap junction protein, beta 2, 26kDa: connexin 26) is a gap junction protein gene that has been implicated in many cases of autosomal recessive non-syndromic deafness. Point and deletion mutations in GJB2 are the most frequent cause of non-syndromic deafness across racial groups. To clarify the relation between profound non-syndromic deafness and GJB2 mutation in Japanese children, we performed genetic testing for GJB2. METHODS: We conducted mutation screening employing PCR and direct sequencing for GJB2 in 126 children who had undergone cochlear implantation with congenital deafness. RESULTS: We detected 10 mutations, including two unreported mutations (p.R32S and p.P225L) in GJB2. We identified the highest-frequency mutation (c.235delC: 44.8%) and other nonsense or truncating mutations, as in previous studies. However, in our research, p.R143W, which is one of the missense mutations, may also show an important correlation with severe deafness. CONCLUSION: Our results suggest that the frequencies of mutations in GJB2 and GJB6 deletions differ among cohorts. Thus, our report is an important study of GJB2 in Japanese children with profound non-syndromic deafness.

A comparison of rainbow trout cell lines for their expression of the major histocompatibility complex genes and the induction of beta-2-microglobulin by dsRNA.

Western blotting with polyclonal antisera to polypeptides of the rainbow trout major histocompatibility (MH) genes and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to compare expression of MH genes in rainbow trout cell lines. One line was the spleen monocyte/macrophage-like RTS11, which grew loosely on plastic surfaces. Adherent cell lines were fibroblast-like RTG-2 from gonads and four epithelial-like cell lines from gill, intestine, liver and hepatoma: RTgill-W1, RTgutGC, RTL-W1, and RTH-149 respectively. All cell lines expressed a 45 kDa MHC class I alpha chain. All cell lines expressed beta-2-microglobulin (beta2m), which was at 11 kDa, but detection was abrogated following trypsinization prior to cell collection. All cell lines expressed transcripts for MH class II alpha and MH class II beta genes; however, MH class II polypeptides were expressed only in RTS11, the only cell line from a lineage of antigen-presenting cells. We report here that double stranded RNA up regulates beta2m and that these cell lines and antisera can be employed for studying MH regulation.

Cochlear implantation in patients with chronic otitis media.

OBJECTIVE: Patients with complications of otitis media present a significant challenge to safe cochlear implantation. We describe our experience of cochlear implantation in patients with chronic ear disease, and propose management principles according to the presenting status of the ear. METHODS: Cochlear implantations were performed as treatment for complications of otitis media in seven patients. They consisted of four patients with adhesive otitis media, two patients with an open cavity after surgery for otitis media and one patient with eosinophilic otitis media. The electrodes were inserted by an approach via the external auditory canal in patients with poor growth of the mastoid antrum or adhesion of the tympanum. For the patients with an open cavity, we created a posterior wall for the external auditory canal and perform the mastoid obliteration. Modified Rambo's technique with blind sac closure of the external auditory canal was performed for the case of eosinophilic otitis media as a single-stage procedure. RESULTS: The post-operative courses were good. However, a post-operative infection developed in one patient who had previously undergone radiation therapy following surgical excision of a cerebellar tumor. CONCLUSION: Transcanal approach is effective in a poorly pneumatized mastoid or severe adhesive otitis media. A decision whether implantation as a single-stage or multiple stages depends on the condition of each cases. But there is a possibility of infection even if we selected a stage operation.

Effects of ibuprofen on the viability and proliferation of rainbow trout liver cell lines and potential problems and interactions in effects assessment.

Under some conditions ibuprofen was either cytotoxic or cytostatic to rainbow trout cell lines: RTL-W1 (liver) and RTH-149 (hepatoma). Ibuprofen at up to 15 microg/mL was not cytotoxic, regardless of dosing protocols, exposure conditions, viability endpoints, or cell lines. Responses to higher ibuprofen concentrations depended on the test methodology. No cytotoxicity was seen when stock ibuprofen solutions had been prepared in ethanol. For stock solutions in dimethylsulfoxide (DMSO), ibuprofen from 50 to 1500 microg/mL elicited little cytotoxicity in cultures in which the final DMSO concentration was 0.05% (v/v), but was consistently cytotoxic after 24 h for cultures with 0.5% DMSO (v/v). Cytotoxicity was evaluated with alamar Blue (AB) and carboxyfluoroscein diacetate acetoxymethyl ester (CFDA-AM) as measures respectively of metabolic activity and membrane integrity. Effective concentrations (EC50s) for ibuprofen with AB and CFDA-AM depended on whether the stock solution was dosed directly into a culture well or mixed in medium prior to being added to a well. For indirect dosing, ibuprofen was more cytotoxic in medium without fetal bovine serum (FBS), whereas for direct dosing ibuprofen was equally cytotoxic in medium with or without FBS. As judged by AB and CFDA-AM EC50s, dosing ibuprofen was directly 10 to 30 times more cytotoxic. In FBS-containing cultures, which was dosed with increasing ibuprofen and DMSO at 0.05% (v/v), cell proliferation was impaired at 50 and 150 microg/mL ibuprofen. Lipopolysaccharide (LPS) at 50 microg/mL had little influence on these cytotoxic and cytostatic effects of ibuprofen in medium with FBS.

Involvement of the incudostapedial joint anomaly in conductive deafness.

CONCLUSION: The outcome of surgery depends on complexities of middle ear anomalies and definite diagnosis can only be achieved during exploratory tympanotomy. We must be aware that the pathology of the congenital ossicular anomalies is variable and careful surgery is needed for hearing improvement. OBJECTIVE: This study aimed to investigate congenital ossicular malformation. SUBJECTS AND METHODS: Fifteen cases of ossicular anomalies without external ear malformation were studied. The anomaly of the incus-stapes complex was the most frequent. There were two cases of fused incudostapedial (IS) joint, which is an extremely rare occurrence. Case 1 was a 33-year-old man, in whom otosclerosis was suspected and exploratory tympanotomy was performed. The IS joint was fused, and the stapes was immobile. Small fenestra stapedectomy was performed. In case 2, a 52-year-old woman, otosclerosis was also suspected and exploratory tympanotomy was performed. The IS joint was fused and the incus was fixed. After the long process of the incus was cut, the stapes became mobile. However, since the incus remained immobile, it was removed and was placed on the stapes. In both cases, the hearing improved after surgery. The averaged hearing gain of 15 cases was 28.8 dB.