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Objectives: Early hearing detection and intervention (EHDI) is critical for achievement of age-appropriate speech perception and language development in hearing-impaired children. It has been 15 years since newborn hearing screening (NHS) was introduced in Japan, and its effectiveness for language development in hearing-impaired children has been extensively studied. Moreover, after over 20 years of cochlear implantation in Japan, many of the prelingual cochlear implant (CI) users have reached school age, and the effect of CI on language development have also been assessed. To identify prognostic factors for language development, audiological/language test scores and demographic factors were compared among prelingual severe-to-profound hearing-impaired children with CI divided into subgroups according to age at first hearing aid (HA) use and whether they received NHS., Methods: Prelingual severe-to-profound deafened children from the Research on Sensory and Communicative Disorders (RSCD) project who met the inclusion criteria were divided into groups according to the age (in months) of HA commencement (before 6 months: group A, after 7 months: group B), and the presence or absence of NHS (groups C and D). Language development and socio-economic data were obtained from audiological/language tests and a questionnaire completed by caregivers, respectively., Results: In total, 210 children from the RSCD project participated in this study. Group A (n=49) showed significantly higher scores on comprehensive vocabulary and academic achievement (p<0.05) than group B (n=161), with no difference in demographics except for significantly older age in group B. No differences in language scores were observed between group C (n=71) and group D (n=129), although participants of group D was significantly older and had used CIs longer (p<0.05)., Conclusions: Early use of HAs until the CI operation may result in better language perception and academic achievement among CI users with prelingual deafness. A long-term follow-up is required to assess the usefulness of NHS for language development., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: Permanent hearing impairment has a life-long impact on children and its early identification is important for language development. A newborn hearing screening (NHS) program has started in Okayama Prefecture, Japan, in 1999 to detect hearing impairment immediately after birth. We aim to examine the effect of this screening program on vocabulary development in pre-school children in a before and after comparative study design., Methods: A total of 107 5-year-old children who graduated from Okayama Kanariya Gakuen (an auditory center for hearing-impaired children) between 1998 and 2011 were enrolled in this study. The pre-NHS group (n=40) was defined as those who graduated between 1998 and 2003, while the post-NHS group (n=67) was defined as those who graduated between 2004 and 2011. The primary outcome was receptive vocabulary, which was assessed by the Picture Vocabulary Test [score <18 (low) vs. score ≥18 (high)]. The secondary outcome was productive vocabulary, or the number of productive words, which was assessed by an original checklist [<1773 words (low) vs. ≥1773 (high)]. We calculated odds ratios and 95% confidence intervals for vocabulary development and compared both groups., Results: The adjusted Picture Vocabulary Test score and number of productive words were significantly higher (p<0.01) in the post-NHS group than the pre-NHS group. Odds ratios were 2.63 (95% confidence interval: 1.17-5.89) for receptive vocabulary and 4.17 (95% confidence interval: 1.69-10.29) for productive vocabulary., Conclusions: The introduction of NHS in Okayama Prefecture significantly improved both receptive and productive vocabulary development in hearing-impaired children., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Endocytic adaptor proteins facilitate cargo recruitment and clathrin-coated pit nucleation. The prototypical clathrin adaptor AP2 mediates cargo recruitment, maturation, and scission of the pit by binding cargo, clathrin, and accessory proteins, including the Eps-homology (EH) domain proteins Eps15 and intersectin. However, clathrin-mediated endocytosis of some cargoes proceeds efficiently in AP2-depleted cells. We found that Dab2, another endocytic adaptor, also binds to Eps15 and intersectin. Depletion of EH domain proteins altered the number and size of clathrin structures and impaired the endocytosis of the Dab2- and AP2-dependent cargoes, integrin β1 and transferrin receptor, respectively. To test the importance of Dab2 binding to EH domain proteins for endocytosis, we mutated the EH domain-binding sites. This mutant localized to clathrin structures with integrin β1, AP2, and reduced amounts of Eps15. Of interest, although integrin β1 endocytosis was impaired, transferrin receptor internalization was unaffected. Surprisingly, whereas clathrin structures contain both Dab2 and AP2, integrin β1 and transferrin localize in separate pits. These data suggest that Dab2-mediated recruitment of EH domain proteins selectively drives the internalization of the Dab2 cargo, integrin β1. We propose that adaptors may need to be bound to their cargo to regulate EH domain proteins and internalize efficiently.

Clathrin-associated endocytic adapters recruit cargoes to coated pits as a first step in endocytosis. We developed an unbiased quantitative proteomics approach to identify and quantify glycoprotein cargoes for an endocytic adapter, Dab2. Surface levels of integrins beta1, alpha1, alpha2, and alpha3 but not alpha5 or alphav chains were specifically increased on Dab2-deficient HeLa cells. Dab2 colocalizes with integrin beta1 in coated pits that are dispersed over the cell surface, suggesting that it regulates bulk endocytosis of inactive integrins. Depletion of Dab2 inhibits cell migration and polarized movement of integrin beta1 and vinculin to the leading edge. By manipulating intracellular and surface integrin beta1 levels, we show that migration speed correlates with the intracellular integrin pool but not the surface level. Together, these results suggest that Dab2 internalizes integrins freely diffusing on the cell surface and that Dab2 regulates migration, perhaps by maintaining an internal pool of integrins that can be recycled to create new adhesions at the leading edge.

Purpose: To evaluate the expression and location of integrin-linked kinase (ILK) within the mouse lens and to characterize the role of this protein during mouse lens epithelial cells (LEC) differentiation in vitro., Methods: Transcription levels of ILK mRNA were determined by RT-PCR in cultured cells and lens tissue. ILK protein was detected by immunoblotting, immunocytochemistry, immunohistochemistry, and immunoprecipitation. A role for ILK in the outgrowth of LEC from dissected mouse lens explants was determined by the use of ILK short interfering RNA (siRNA). Affinity-purified polyclonal anti-recombinant human ILK IgG was prepared and characterized for these experiments. A comparison of several anti-ILK antibodies was performed by immunoblotting, immunoprecipitation, and ELISA., Results: ILK was transcribed in LEC and lens fiber cells in vivo. ILK protein was expressed in the differentiating LEC at the equatorial region of the lens and, to a lesser extent, within the cortical and nuclear fiber cells. LEC in vitro produced copious ILK, which exhibited a filamentous pattern throughout the cytoplasm. The expression of ILK was increased during epithelial-mesenchymal-transition (EMT) of LEC from lens explants, whereas inhibition of ILK by siRNA delayed expression of the EMT markers smooth muscle alpha-actin and fibronectin., Conclusions: Analysis of ILK expression, localization, and activity in the mouse lens and cultured LEC is substantially facilitated by the generation of a multi-functional, polyclonal, affinity-purified anti-ILK antibody. Expressed in most tissues and cells lines, ILK is unexpectedly restricted to the equatorial LEC and differentiated fiber cells of the mouse lens. The occurrence of ILK expression with LEC differentiation is consistent with the positive regulatory function of ILK, which is revealed in a model of EMT in vitro. This is the first study to show the expression of ILK in the lens and its unique distribution pattern within cultured lens epithelia.

Objective: The monosyllable speech perception ability after years of educational intervention was compared between prelingually deafened pediatric hearing aid users and their cochlear implant counterparts., Design: An open-set monosyllabic speech perception test was conducted on all subjects. The test required subjects to indicate a corresponding Japanese character to that spoken by the examiner. Fifty-two subjects with prelingual hearing impairment (47 hearing aid users and 5 cochlear implant users) were examined., Results: Hearing aid users with average pure-tone thresholds less than 90 dB HL demonstrated generally better monosyllable perception than 70%, which was equivalent or better performance than that of the cochlear implant group. Widely dispersed speech perception was observed within the 90-99 dB HL hearing-aid user group with most subjects demonstrating less than 50% speech perception. In the cluster of >100 dB HL, few cases demonstrated more than 50% in speech perception. The perception ability of the vowel part of each mora within the cochlear implant group was 100% and corresponding to that of hearing aid users with moderate and severe hearing loss., Conclusion: Hearing ability among cochlear implant users can be comparable with that of hearing aid users with average unaided pure-tone thresholds of 90 dB HL, after monosyllabic speech perception testing was performed.

The presence of additional handicaps in hearing-impaired children makes the prediction of language ability after cochlear implantation unreliable. Only limited follow-up data on developmental improvement after implantation among multiply handicapped children is available. The present study reports the course of development (audiological and linguistic) after cochlear implantation in one subject with moderate mental retardation. Preoperatively, his language development showed 34 months delay when compared to chronological age. The difference had shortened to 23 months by 2 years post-surgery. The subject's cognitive delay had not changed upon 2-year follow-up. The cochlear implant can be credited to his improvement in language development.

We established HLA-peptide binding assay system, using biotinylated peptide and HLA class II transfectants to make clear the interaction of peptides and HLA molecules. By using this system and T cell proliferation assay, we analyzed the effect of polymorphism of DR4 subtypes on responding to M12(4) peptide which derived from M12 protein of Streptococcus. We found amino acid residue which determines T cell recognition is DR beta-74 (Glutamate to Alanine) on this peptide. Using this system, we expect to understand the mechanisms of immune response associated with HLA class II molecules.