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Mutations in the OTOF gene are a common cause of hereditary hearing loss and the main cause of auditory neuropathy spectrum disorder (ANSD). Although it is reported that most of the patients with OTOF mutations have stable, congenital or prelingual onset severe-to-profound hearing loss, some patients show atypical clinical phenotypes, and the genotype–phenotype correlation in patients with OTOF mutations is not yet fully understood. In this study, we aimed to reveal detailed clinical characteristics of OTOF-related hearing loss patients and the genotype–phenotype correlation. Detailed clinical information was available for 64 patients in our database who were diagnosed with OTOF-related hearing loss. As reported previously, most of the patients (90.6%) showed a “typical” phenotype; prelingual and severe-to-profound hearing loss. Forty-seven patients (73.4%) underwent cochlear implantation surgery and showed successful outcomes; approximately 85–90% of the patients showed a hearing level of 20–39 dB with cochlear implant and a Categories of Auditory Performance (CAP) scale level 6 or better. Although truncating mutations and p.Arg1939Gln were clearly related to severe phenotype, almost half of the patients with one or more non-truncating mutations showed mild-to-moderate hearing loss. Notably, patients with p.His513Arg, p.Ile1573Thr and p.Glu1910Lys showed “true” auditory neuropathy-like clinical characteristics. In this study, we have clarified genotype–phenotype correlation and efficacy of cochlear implantation for OTOF-related hearing loss patients in the biggest cohort studied to date. We believe that the clinical characteristics and genotype–phenotype correlation found in this study will support preoperative counseling and appropriate intervention for OTOF-related hearing loss patients.

[Purpose] This study investigated the relationship between the single-leg stance test with light touch and hip rotator muscle strength. [Participants and Methods] Thirty-one healthy young adults participated in the study. A single leg stance test with light touch was performed to evaluate the participants' static balance ability. The duration that an individual could successfully perform the single leg stance test with light touch in the eyes open was measured. The participants were instructed to slightly touch their right index fingertip on the digital scale. The hip muscle strength of the internal rotators and external rotators were measured by the isometric peak torque. The internal/external rotator strength ratio was calculated by dividing the strength of the internal rotator by that of the external rotator. [Results] The hip external rotator muscle strength was higher in males than in females. Moreover, there was a significant correlation between the single-leg stance test with light touch and hip external rotator muscle strength in males and between the single leg stance test with light touch and hip internal rotator muscle strength in females. Furthermore, a significant positive correlation was found between the single leg stance test with light touch and hip internal rotator/external rotator ratio in males. [Conclusion] We concluded that the single leg stance test with light touch is a useful tool to evaluate static hip muscle strength.

The optimal dosage of methotrexate (MTX) for graft-versus-host disease (GVHD) prophylaxis after cord blood transplantation (CBT) has not been well elucidated. Therefore, we conducted a retrospective study comparing a mini-MTX group (5 mg/m2 on day 1, 3 and 6) to a short-MTX group (10 mg/m2 on day 1 and 7 mg/m2 on day 3 and 6) after CBT. Sixty-three patients were classified as the mini-MTX group and 20 as the short-MTX group. The median time and cumulative incidence of neutrophil engraftment did not vary between the two groups. The cumulative incidence of grade 2–4 and grade 3–4 acute GVHD was similar in both groups. Overall survival in the mini-MTX group was significantly lower than in the short-MTX group (46.9% vs. 88.7% at 1 year, p

Cathodal transcranial direct current stimulation (C-tDCS) is generally assumed to inhibit cortical excitability. The parietal cortex contributes to multisensory information processing in the postural control system, and this processing is proposed to be different between the right and left hemispheres and sensory modality. However, previous studies did not clarify whether the effects of unilateral C-tDCS of the parietal cortex on the postural control system differ depending on the hemisphere. We investigated the changes in static postural stability after unilateral C-tDCS of the parietal cortex. Ten healthy right-handed participants were recruited for right- and left-hemisphere tDCS and sham stimulation, respectively. The cathodal electrode was placed on either the right or left parietal area, whereas the anodal electrode was placed on the contralateral forehead. We evaluated static standing balance by measuring the sway path length, mediolateral (ML) sway, anteroposterior (AP) sway, sway area, and the sway path length per unit area (L/A) after 15-minute C-tDCS under eyes open (EO) and closed (EC) conditions. C-tDCS over the right hemisphere significantly increased the sway path length, ML sway, and sway area in the EO condition. In contrast, C-tDCS over the left hemisphere significantly increased the L/A in both the EC and EO condition. These results suggest that the right parietal region contributes to static standing balance through chiefly visual information processing during the EO condition. On the other hand, L/A increase during EC and EO by tDCS over the left parietal region depends more on somatosensory information to maintain static standing balance during the EC condition.

[Purpose] The thoracolumbar supraspinous intersegmental tenderness test (ITT) in the segment above was performed to compare spinal alignment and autonomic activity in the presence or absence of pain. [Participants and Methods] Thirty young males were grouped into Th1-4 (Cardiopulmonary visceral nerves), Th5-9 (Large visceral nerve), and Th10-12 (Small visceral nerve) by ITT for the presence of pain. Measurements of the spinal alignment and autonomic function were performed. [Results] Those with ITT pain had a significantly lower range of motion in the sagittal plane at Th12, Th12-L1, and L2-3 and in the frontal plane at Th1-2, Th4-5, Th6-7, and L3-4 than those in the no pain group. On autonomic function tests, the pain group had significantly lower Total Power, LF (Low Frequency), and CVRR (Coefficient of variation of R-R interval). [Conclusion] In ITT, patients with pain at Th5-9 have a mixture of reduced sagittal tilt angle and autonomic hypofunction of the adjacent upper and lower thoracic to lumbar vertebrae.

Detailed studies have not been conducted on sound localization and speech perception in noise in patients with unilateral congenital aural atresia (UCAA).To evaluate the benefits of the use of the Vibrant Soundbridge (VSB) for UCAA by performing audiometric and sound localization tests.Four children with UCAA underwent VSB (VORP 503) implantation from 2018 to 2019. Speech perception tests in noise were conducted using the Japanese monosyllable test. The spatial configuration for speech testing consisted of speech presented from the front and noise presented into the normal ear (SThe children's speech perception in noise 6 months after VSB activation was significantly better than before activation (The benefits of VSB use in children with UCAA were revealed using audiometric and sound localization tests.

Intermittent theta-burst stimulation (iTBS) using transcranial magnetic stimulation (TMS) is known to produce excitatory after-effects over the primary motor cortex (M1). Recently, transcranial alternating current stimulation (tACS) at 10 Hz (α) and 20 Hz (β) have been shown to modulate M1 excitability in a phase-dependent manner. Therefore, we hypothesized that tACS would modulate the after-effects of iTBS depending on the stimulation frequency and phase. To test our hypothesis, we examined the effects of α- and β-tACS on iTBS using motor evoked potentials (MEPs). Eighteen and thirteen healthy participants were recruited for α and β tACS conditions, respectively. tACS electrodes were attached over the left M1 and Pz. iTBS over left M1 was performed concurrently with tACS. The first pulse of the triple-pulse burst of iTBS was controlled to match the peak (90°) or trough (270°) phase of the tACS. A sham tACS condition was used as a control in which iTBS was administered without tACS. Thus, each participant was tested in three conditions: the peak and trough of the tACS phases and sham tACS. As a result, MEPs were enhanced after iTBS without tACS (sham condition), as observed in previous studies. α-tACS suppressed iTBS effects at the peak phase but not at the trough phase, while β-tACS suppressed the effects at both phases. Thus, although both types of tACS inhibited the facilitatory effects of iTBS, only α-tACS did so in a phase-dependent manner. Phase-dependent inhibition by α-tACS is analogous to our previous finding in which α-tACS inhibited MEPs online at the peak condition. Conversely, β-tACS reduced the effects of iTBS irrespective of its phase. The coupling of brain oscillations and tACS rhythms is considered important in the generation of spike-timing-dependent plasticity. Additionally, the coupling of θ and γ oscillations is assumed to be important for iTBS induction through long-term potentiation (LTP). Therefore, excessive coupling between β oscillations induced by tACS and γ or θ oscillations induced by iTBS might disturb the coupling of θ and γ oscillations during iTBS. To conclude, the action of iTBS is differentially modulated by neuronal oscillations depending on whether α- or β-tACS is applied.

Transcranial alternating current stimulation (tACS) at 20 Hz (β) has been shown to modulate motor evoked potentials (MEPs) when paired with transcranial magnetic stimulation (TMS) in a phase-dependent manner. Repetitive paired-pulse TMS (rPPS) with I-wave periodicity (1.5 ms) induced short-lived facilitation of MEPs. We hypothesized that tACS would modulate the facilitatory effects of rPPS in a frequency- and phase-dependent manner. To test our hypothesis, we investigated the effects of combined tACS and rPPS. We applied rPPS in combination with peak or trough phase tACS at 10 Hz (α) or β, or sham tACS (rPPS alone). The facilitatory effects of rPPS in the sham condition were temporary and variable among participants. In the β tACS peak condition, significant increases in single-pulse MEPs persisted for over 30 min after the stimulation, and this effect was stable across participants. In contrast, β tACS in the trough condition did not modulate MEPs. Further, α tACS parameters did not affect single-pulse MEPs after the intervention. These results suggest that a rPPS-induced increase in trans-synaptic efficacy could be strengthened depending on the β tACS phase, and that this technique could produce long-lasting plasticity with respect to cortical excitability.

The 27th International Liquid Crystal Conference (ILCC2018) was held in Kyoto from 22 to 27 July 2018. The venue was Kyoto International Conference Center (Figure 1) in which many significant inter...

[Purpose] Previous studies have reported that the nervous system is influenced during short-term cast immobilization. However, the effects of short-term inactivity on somatosensory information processing systems are not well understood. This study investigated the effect of 10 h of upper limb immobilization on the somatosensory pathway using short-latency somatosensory evoked potentials. [Participants and Methods] Twenty right-handed healthy participants (mean age 21.7 years) were enrolled in this study. The participants’ left hands and forearms were wrapped in a soft bandage at a 90° elbow flexed position. The participants were instructed not to move their left hand for 10 h. To obtain short-latency somatosensory evoked potentials, we used a multimodal evoked potential system. The left median nerve was electrically stimulated at a rate of 5 Hz for a duration of 0.2 ms. The intensity of the stimulus was adjusted to induce mild twitches of the thumb. The amplitudes and latencies of the short-latency somatosensory evoked potential components (N9, N13, and N20) were measured before and after immobilization. [Results] The amplitude of the N9 component significantly increased after immobilization. [Conclusion] Our results indicated that the changes in the excitability of the peripheral somatosensory nerve were due to 10 h of inactivity.

[Purpose] This study aimed to examine the direct and indirect effects of factors influencing the risk of life space assessment using path analysis. [Participants and Methods] A sample of 212 elderly residents (at least 65 years old) with no clear indications of cognitive dysfunction, visual impairment, and physical dysfunction were recruited for the study. Data on these factors were collected from the participants at a community gathering using measures of life space assessment, skeletal muscle mass, lower extremity muscle strength, mobility, cognitive function, and fear of falling. Correlational and path analyses were used to investigate the relationships between these variables. [Results] The final path model satisfied the requisite statistical criteria, and subsequently, the relationships between the physiological and psychological factors associated with life space assessment were structured and represented visually. Age, skeletal muscle mass, fear of falling, and mobility had a direct effect on life space assessment, whereas lower extremity muscle strength and cognitive function affected it indirectly. [Conclusion] In this study, direct and indirect effects of physiological and psychological factors related to risk of life space assessment of the elderly were clarified using path analysis.

MYO6 is known as a genetic cause of autosomal dominant and autosomal recessive inherited hearing loss. In this study, to clarify the frequency and clinical characteristics of hearing loss caused by MYO6 gene mutations, a large-scale genetic analysis of Japanese patients with hearing loss was performed. By means of massively parallel DNA sequencing (MPS) using next-generation sequencing for 8074 Japanese families, we found 27 MYO6 variants in 33 families, 22 of which are novel. In total, 2.40% of autosomal dominant sensorineural hearing loss (ADSNHL) in families in this study (32 out of 1336) was found to be caused by MYO6 mutations. The present study clarified that most cases showed juvenile-onset progressive hearing loss and their hearing deteriorated markedly after 40 years of age. The estimated hearing deterioration was found to be 0.57 dB per year, when restricted to change after 40 years of age, the deterioration speed was accelerated to 1.07 dB per year. To obtain supportive evidence for pathogenicity, variants identified in the patients were introduced to MYO6 cDNA by site-directed mutagenesis and overexpressed in epithelial cells. They were then assessed for their effects on espin1-induced microvilli formation. Cells with wildtype myosin 6 and espin1 co-expressed created long microvilli, while co-expression with mutant constructs resulted in severely shortened microvilli. In conclusion, the present data clearly showed that MYO6 is one of the genes to keep in mind with regard to ADSNHL, and the molecular characteristics of the identified gene variants suggest that a possible pathology seems to result from malformed stereocilia of the cochlear hair cells.

[Purpose] To study the effect that limbering up of the muscles attached to the pelvis has on muscle strength of the trunk and upper and lower extremities, which are not being exercised, and to investigate the possibilities for clinical application. [Subjects and Methods] A total of 152 healthy adult men. Sthenometry was conducted using a handheld dynamometer to assess the effect of limbering up of the upper gluteus maximus, hamstrings, and internal abdominal oblique muscles attached to thoracolumbar fascia on the trunk and upper and lower extremities. The exercises were slowly performed 20 repetitions. Subjects were divided into AB group (n=49) measuring abdominal and back muscle strength, K group (n=42) measuring knee flexor and extensor strength, and S group (n=61) measuring shoulder flexor and external rotator strength and compared to non-exercising controls. [Results] In the exercise groups, exercising either gluteus maximus or hamstrings significantly increased the strength of abdominal and back muscles; exercising gluteus maximus increased knee extensor strength, and exercising the abdominal internal oblique muscle significantly increased knee flexor strength; and shoulder flexor strength significantly increased after exercising gluteus maximus versus controls. [Conclusion] This may be useful in rehabilitation of injuries to the trunk and upper and lower extremities.

The effects of vestibular rehabilitation on poststroke patients are unknown. This study aimed to investigate whether or not vestibular rehabilitation would improve both the vestibulo-ocular reflex and gait performance of patients with poststroke hemiparesis. Twenty-eight patients with stroke were assigned randomly to either an experimental group (N=14) or a control group (N=14). The experimental group performed the conventional physical therapy for 40 min and vestibular rehabilitation for 20 min, as a 60 min session, during the first 3 weeks and then completed only the conventional intervention for 60 min for the following 3 weeks. The control group performed only the 60 min conventional physical therapy for 6 weeks. Both groups were measured using the gaze stabilization test, the 10 m walking test, the timed up and go test, and the dynamic gait index. Patients were assessed at baseline, and at 3 and 6 weeks. Although the control group showed no significant difference in any outcome measures, the experimental group showed an improvement in gaze stabilization test scoring, which increased significantly after 3 weeks compared with the baseline (P=0.030). The dynamic gait index was also significantly increased after 3 and 6 weeks compared with the baseline (P=0.049 and 0.024, respectively). This study indicated that vestibular rehabilitation might improve poststroke patients' vestibulo-ocular reflex. Moreover, patients might show improved gait performance at least up to 3 weeks after the vestibular intervention by the sensory reweight to coordinate vestibular input.

The vestibulo-ocular reflex (VOR) exerts a significant influence on gait performance. Therefore, a decrease in VOR function could worsen gait impairments in patients with poststroke hemiparesis. The effects of decreased VOR function on gait performance could be further exacerbated by aging-related physical weakness and impaired motor function of the hemiparetic lower limb. The aim of our study was to evaluate the possible synergistic effect of aging and impairment in lower extremity function and the VOR on walking ability of poststroke hemiplegic patients. The VOR was evaluated, using the gaze-stabilization test (GST), in 75 patients with a poststroke hemiplegia. Lower extremity function was assessed using the Fugl-Meyer assessment (FMA-LE). Gait performance was evaluated using the 10-m walking test, the timed up-and-go, and the dynamic gait index (DGI). The relationships between gait performance and age, FMA-LE and GST, as well as whether age, FMA-LE, and/or GST were significant predictors of gait performance were evaluated. The 10-m walking test, timed up-and-go and DGI were significantly correlated to the FMA-LE and GST (P

Variants of the LOXHD1 gene, which are expressed in hair cells of the cochlea and vestibule, have been reported to cause a progressive form of autosomal recessive non-syndromic hereditary hearing loss, DFNB77. In this study, genetic screening was conducted on 8074 Japanese hearing loss patients utilizing massively parallel DNA sequencing to identify individuals with LOXHD1 variants and to assess their phenotypes. A total of 28 affected individuals and 21 LOXHD1 variants were identified, among which 13 were novel variants. A recurrent variant c.4212 + 1G &gt, A, only reported in Japanese patients, was detected in 18 individuals. Haplotype analysis implied that this variation occurred in a mutational hot spot, and that multiple ancestors of Japanese population had this variation. Patients with LOXHD1 variations mostly showed early onset hearing loss and presented different progression rates. We speculated that the varying severities and progression rates of hearing loss are the result of environmental and/or other genetic factors. No accompanying symptoms, including vestibular dysfunction, with hearing loss were detected in this study. Few studies have reported the clinical features of LOXHD1-gene associated hearing loss, and this study is by far the largest study focused on the evaluation of this gene.