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To evaluate the clinical factors associated with the outcome of tonsillectomy in children with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, thereby clarifying who would most likely benefit from that surgery.This was a case-control study of 53 PFAPA patients who underwent tonsillectomy and were divided into a complete-resolution group and a postoperative-fever group. Logistic regression analyses were performed using 17 clinical factors as variables to identify factors associated with the surgical outcome. Hierarchical cluster analysis was also performed to evaluate for relationships between phenotypes and surgical outcomes.Thirty-nine (73.6%) patients had complete resolution after tonsillectomy. In simple logistic regression analysis, the surgical outcome showed significant positive trends with late-onset (odds ratio [OR] 7.1, P = 0.02) and presence of headache (OR 6.5, P = 0.01). In stepwise multiple logistic regression analysis adjusted for age at onset, presence of headache was significantly associated with complete resolution (OR 6.5, P = 0.01). The complete resolution rates for each combination of headache status and age at onset were as follows: presence of headache/age at onset ≥36 months, 100% (14/14); presence of headache/age at onset36 months, 76.9% (10/13); absence of headache/age at onset ≥36 months, 75.0% (6/8); and absence of headache/age at onset36 months, 43.8% (7/16). In hierarchical cluster analysis, complete resolution, age at onset, and headache were in the same cluster.PFAPA patients with headache and late onset responded well to tonsillectomy. The mechanisms underlying this association may warrant further investigation.

Tracheal atresia causes some secondary changes (dilated trachea, flattened/inverted diaphragm, hyperintense and hyperinflated lungs). They can be reduced if a high airway fistula is present. This study evaluated fetal MR images of tracheal atresia and the secondary changes, focusing on the presence of a fistula. We assessed fetal MR images of tracheal atresia without fistula (n=4, median 26 weeks), tracheal atresia with fistula (n=4, median 33 weeks) and controls (n=30, median 32 weeks). We evaluated airway obstruction using true-positive rate in tracheal atresia and false-positive rate in controls indicating they are likely normal variants. Tracheal diameter, craniocaudal-anteroposterior ratio of the right hemidiaphragm, lung-to-liver signal intensity ratio, and cardiothoracic ratio were compared among the three groups using the Kruskal-Wallis test followed by pairwise comparison using the Mann-Whitney U test. True-positive rate was 100% in tracheal atresia, while false-positive rate was 20% in controls. The Kruskal-Wallis test showed differences among groups in craniocaudal-anteroposterior ratio and cardiothoracic ratio (P

Objectives The present study analyzed surgical outcomes of laryngotracheal separation (LTS) in children with neurological disorders. The purpose of this study was to investigate respiratory impairment and severe complications after LTS in children, and identify the possibility of permanent tracheostomy without a tracheostomy tube as the safest respiratory management method. Methods Twenty‐eight patients (male:female = 16:12) with neurological disorders (6 months to 32 years) who underwent LTS between January 2012 and April 2018 were reviewed. Tracheal diameter, Cobb angle, and sternocervical spine distance (SCD) were measured to assess the potential risk and possibility of removing tracheostomy tube management. Results Tracheostomy tube could be removed shortly after LTS in 57% (16/28). However, nine of these patients developed respiratory problems that required tracheostomy tube placement 2 years after LTS. New requirements for a tracheostomy tube as a stent were strongly correlated with SCD (P 1) as well as tracheal deformity. Conclusions Respiratory management in neurologically impaired children after LTS without a tracheostomy tube is challenging because thoracic deformity during physical growth affects tracheal disfiguration. Thoracic deformities and progression of scoliosis should be considered in respiratory management approaches in children with neurological disorders, and long‐term follow‐up by computed tomography is necessary. LEVEL OF EVIDENCE IV

The purpose of this study is to profile the clinical and genetic features of Japanese Waardenburg syndrome (WS) patients and validate the W index. Sixteen Japanese WS families with congenital sensorineural hearing loss were included in the study. The inner canthal, interpupillary, and outer canthal distances (ICD, IPD, and OCD) were measured for all patients, and patients were screened for presence of PAX3, MITF, SOX10, and EDNRB mutations. The WS patients were clinically classified under the current W index as follows: 13 families with WS1, 2 families with WS2, and 1 family with WS4. In the 13 WS1 families, genetic tests found PAX3 mutations in 5 families, MITF mutations in 4 families, SOX10 mutations in 3 families, and EDNRB mutations in 1 family. 61% of clinically classified WS1 patients under the current W index conflicted with the genetic classification, which implies W index is not appropriate for Japanese population. Resetting the threshold of W index or novel index formulated with ethnicity matched samples is necessary for clinical classification which is consistent with genetic classification for WS patients with distinct ethnicity.

Objectives Auditory neuropathy (AN) is a clinical disorder characterized by the absence of auditory brainstem response and presence of otoacoustic emissions. A gradual loss of otoacoustic emissions has been reported for some cases of AN. Such cases could be diagnosed as cochlear hearing loss and lead to misunderstanding of the pathology when patients first visit clinics after the loss of otoacoustic emissions. The purpose of this study was to investigate the time course of changes in distortion product otoacoustic emissions (DPOAEs) in association with patients' genetic and clinical backgrounds, including the use of hearing aids. Design DPOAE measurements from 31 patients with AN were assessed. Genetic analyses for GJB2, OTOF, and mitochondrial m.1555A> G and m.3243A> G mutations were conducted for all cases, and the analyses for CDH23 and OPA1 were conducted for the selected cases. Patients who were younger than 10 years of age at the time of AN diagnosis were designated as the pediatric AN group (22 cases), and those who were 18 years of age or older were designated as the adult AN group (9 cases). DPOAE was measured at least twice in all patients. The response rate for DPOAEs was defined and analyzed. Results The pediatric AN group comprised 10 patients with OTOF mutations, 1 with GJB2 mutations, 1 with OPA1 mutation, and 10 with indefinite causes. Twelve ears (27%) showed no change in DPOAE, 20 ears (46%) showed a decrease in DPOAE, and 12 ears (27%) lost DPOAE. Loss of DPOAE occurred in one ear (2%) at 0 years of age and four ears (9%) at 1 year of age. The time courses of DPOAEs in patients with OTOF mutations were divided into those with early loss and those with no change, indicating that the mechanism for deterioration of DPOAEs includes not only the OTOF mutations but also other common modifier factors. Most, but not all, AN patients who used hearing aids showed deterioration of DPOAEs after the start of using hearing aids. A few AN patients also showed deterioration of DPOAEs before using hearing aids. The adult AN group comprised 2 patients with OPA1 mutations, 2 with OTOF mutations, and 5 with indefinite causes. Four ears (22%) showed no change in DPOAE, 13 ears (72%) showed a decrease, and one ear (6%) showed a loss of DPOAE. Although the ratio of DPOAE decrease was higher in the adult AN group than in the pediatric AN group, the ratio of DPOAE loss was lower in the adult AN group. DPOAE was not lost in all four ears with OPA1 mutations and in all four ears with OTOF mutations in the adult group. Conclusions DPOAE was decreased or lost in approximately 70% of pediatric and about 80% of adult AN patients. Eleven percent of pediatric AN patients lost DPOAEs by 1 year of age. Genetic factors were thought to have influenced the time course of DPOAEs in the pediatric AN group. In most adult AN patients, DPOAE was rarely lost regardless of the genetic cause.

Hereditary hearing loss is challenging to diagnose because of the heterogeneity of the causative genes. Further, some genes involved in hereditary hearing loss have yet to be identified. Using whole-exome analysis of three families with congenital, severe-to-profound hearing loss, we identified a missense variant of SLC12A2 in five affected members of one family showing a dominant inheritance mode, along with de novo splice-site and missense variants of SLC12A2 in two sporadic cases, as promising candidates associated with hearing loss. Furthermore, we detected another de novo missense variant of SLC12A2 in a sporadic case. SLC12A2 encodes Na+, K+, 2Cl− cotransporter (NKCC) 1 and plays critical roles in the homeostasis of K+-enriched endolymph. Slc12a2-deficient mice have congenital, profound deafness; however, no human variant of SLC12A2 has been reported as associated with hearing loss. All identified SLC12A2 variants mapped to exon 21 or its 3’-splice site. In vitro analysis indicated that the splice-site variant generates an exon 21-skipped SLC12A2 mRNA transcript expressed at much lower levels than the exon 21-included transcript in the cochlea, suggesting a tissue-specific role for the exon 21-encoded region in the carboy-terminal domain. In vitro functional analysis demonstrated that Cl− influx was significantly decreased in all SLC12A2 variants studied. Immunohistochemistry revealed that SLC12A2 is located on the plasma membrane of several types of cells in the cochlea, including the strial marginal cells, which are critical for endolymph homeostasis. Overall, this study suggests that variants affecting exon 21 of the SLC12A2 transcript are responsible for hereditary hearing loss in humans., Author summary Sounds are perceived by auditory sensory cells, owing to tissues surrounding them, including the cochlear lateral wall. Part of the cochlear lateral wall, the stria vascularis, is critical for production and maintenance of inner-ear fluid with a high potassium concentration, and for generating the positive voltage in the inner ear, important for sound perception, by stimulating secretion of potassium from marginal cells. The gene SLC12A2 encodes a protein involved in sodium, potassium, and chloride transport essential for proper function of specific cells in the stria vascularis; however, human variants of SLC12A2 have not previously been associated with hearing loss. By comprehensive genetic analysis of protein-coding sequences, we identified four candidate changes in SLC12A2 in four families with congenital, severe-to-profound hearing loss. Intriguingly, all four genetic variants were either within or at the 3’-splice site of the exon 21 which encodes a part of the carboxy terminal intracellular domain of SLC12A2. Experiments in cultured cells showed that skipping or mutation of exon 21 significantly decreased chloride influx mediated by the SLC12A2 protein. Overall, our results strongly indicate that mutations influencing exon 21 of SLC12A2 represent a novel mechanism underlying deafness in humans.

Objective Variants in GJB2 can cause autosomal recessive deafness (DFNB1). There is evidence for genotype–phenotype correlations of GJB2 variants; however, several genotypes can cause varying levels of hearing loss likely attributable to differences in genetic or environmental background. As siblings share approximately 50% of their genetic background and usually have a common environmental background, analysis of phenotypes of siblings with a specific GJB2 variant may reveal factors relevant to phenotypic variation. There have been no previous analyses of differences in hearing among siblings carrying a single GJB2 genotype. Here, we investigated hearing differences between siblings with a single GJB2 variant, which can cause various levels of hearing loss. Methods We examined hearing levels in 16 pairs of siblings homozygous for the c.235delC variant of GJB2. Differences in hearing acuity between sibling pairs were detected by auditory evaluation. Results Average differences in acoustic threshold >30 dB were observed between five pairs of siblings, whereas the remaining 11 pairs had average threshold values within approximately 10 dB of one another. Hearing loss varied from moderate to profound. Conclusion Our results indicate that auditory acuity associated with homozygosity for GJB2 c.235delC can vary in degree; however, in approximately 70% of younger siblings, it was approximately the same as that in the first child, despite a diverse spectrum of hearing loss among different families. These results suggest that differences in genetic background may modify the phenotype associated with homozygous GJB2 c.235delC.

Congenital high airway obstruction syndrome (CHAOS) is a rare congenital anomaly and the most common etiology is laryngeal atresia. Recently, an increasing number of cases have survived due to prenatal diagnosis and pre- and peri-natal care including ex-utero intrapartum treatment (EXIT). More than 100 cases of CHAOS have been reported, and about half of them were complicated with associated anomalies. Here we report a very rare case of prenatally diagnosed CHAOS (laryngeal atresia) complicated with esophageal atresia, tracheoesophageal fistula (TEF) and duodenal atresia, and the patient was saved by EXIT. This combination of anomalies resulted in a very confusing prenatal diagnosis with unique imaging feature of the fetus.

Objective Evaluating the prevalence of specific gene mutations associated with a certain audiometric configuration facilitates clinical assessment of patients with sensorineural hearing loss (SNHL). WFS1 is responsible for autosomal dominant nonsyndromic deafness 6/14/38 and is the most frequent genetic cause of low-frequency SNHL (LFSNHL); however, the exact prevalence of WFS1 mutations in LFSNHL is unknown. Therefore, we evaluated genetic mutations and clinical features in patients with nonsyndromic bilateral LFSNHL, focusing on the WFS1. Study Design Retrospective case series from 2002 to 2013 at the National Hospital Organization Tokyo Medical Center and collaborating hospitals. Methods WFS1, GJB2, and mitochondrial DNA mutation screening was carried out for 74 of 1,007 Japanese probands with bilateral LFSNHL. Results WFS1 and GJB2 mutations were identified in eight of 74 cases (10.8%). Four cases had heterozygous WFS1 mutations; one case had a heterozygous WFS1 mutation and a heterozygous GJB2 mutation; and three cases had biallelic GJB2 mutations. Three cases with WFS1 mutations were sporadic; two of them were confirmed to be caused by a de novo mutation based on the genetic analysis of their parents. In the case with mutations in both WFS1 and GJB2, a de novo mutation of WFS1 was confirmed in the proband's mother by genetic screening of the mother's parents. Conclusion Genetic screening focusing on LFSNHL has not been conducted. The present study first revealed the prevalence of specific gene mutations. WFS1 autosomal dominant mutations were identified even in sporadic cases. Our results also suggested a mutational hotspot in WFS1. Level of Evidence 4. Laryngoscope, 127:E324–E329, 2017

The periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is an autoinflammatory disease, characterized, as its name suggests, by periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis. This syndrome is the most common cause of recurrent fever in children, however the rate of recognition of this syndrome is still low. Tonsillectomy has been suggested as an effective treatment, even though the precise, pathophysiology underlying this syndrome remains unknown. In this study, we investigated the outcomes in patients who underwent tonsillectomy. In particular, we examined the surgical outcomes and clinical features of the patients who underwent tonsillectomy. A total of 19 patients with PFAPA syndrome underwent tonsillectomy at our hospital from July 2013 to May 2016. Before the surgery, while all the patients had received medications, none showed complete resolution of the syndromes. However, of the 19 patients, 15 showed complete resolution of the syndrome immediately after the surgery. Four patients had fever even after the surgery. Three patients showed partial remission, with the frequency and duration of the episodes decreasing after the surgery. However, in one patient, the fever persisted as before the surgery. There were no significant differences in the clinical characteristics, such as the age at onset, fever episodes, associated symptoms, or age at surgery among the three groups. However, we observed a trend towards a higher frequency of a family history in patients with persistent symptoms after surgery. Tonsillectomy was highly effective against PFAPA syndrome, however, some patients failed to respond to the procedure. Therefore, it is important to carefully evaluate the risks and benefits in each case. The indications for tonsillectomy have not yet been clearly established. It is essential to continue further investigations to establish effective therapeutic strategies for this syndrome.

Objective Hearing loss caused by GJB2 mutations is inherited in an autosomal recessive manner (DFNB1); thus siblings of an affected child have a 25% chance of also being affected. Hearing loss among subsequent siblings carrying the same GJB2 mutation is a concern for parents and a frequent topic of enquiry during genetic counseling. Evidence exists for genotype-phenotype correlations of GJB2 mutations; however, no analysis of differences in hearing among siblings, in whom the common genetic background may decrease variation, has been reported. The purpose of the present study was to investigate hearing differences between siblings with identical GJB2 mutations. Methods We examined the hearing levels of 12 pairs of siblings; each pair had the same pathogenic GJB2 mutations. Differences in hearing acuity between sibling pairs detected by auditory evaluation. Results No significant correlation was detected between the average hearing levels of first and second affected siblings. Average differences in acoustic threshold >30 dB were observed between four pairs of siblings, whereas the remaining eight pairs had average threshold values within 20 dB of one another. Conclusion Our results indicate that auditory acuity would be expected to approximate that found in the first child in approximately 70% of subsequent children with GJB2-mediated hearing loss, whereas 30% of subsequent siblings would have average differences of >30 dB.

Background Sleep disordered breathing (SDB) is defined as a series of disorders including snoring, obstructive sleep apnea, and hypopnea. Few studies investigated the incidence of SDB following primary palatoplasty with objective testing. The aims of this study were to elucidate the prevalence and degree of SDB approximately 1 week following primary palatoplasty with objective testing and to clarify the risk factors. Method A retrospective review was performed on children who underwent primary palatoplasty between April 2013 and July 2017 at National Center for Child Health and Development, Tokyo, Japan. As a national center, the authors accept many syndromic patients. The authors keep all patients after palatoplasty intubated and observe them overnight in intensive care unit to reduce the risks of respiratory events. Patients were evaluated with overnight pulse oximetry on 5 to 7 days postoperatively. Results Forty-four patients were included, and 30% of the patients were associated with congenital anomaly. Thirteen patients (30%) were diagnosed with SDB. None of the patients required additional treatment after the evaluation. Laryngomalacia and postoperative oxygen requirement significantly correlated with postoperative SDB. Conclusion Approximately one-third of the patients may be at the risk of SDB 1 week after primary palatoplasty. Patients with history of laryngomalacia or those who required oxygen support for prolonged time after primary palatoplasty should be cared for significantly high risk of postoperative SDB.

We investigated the effect of treatment with hot water extracts from the spent mushroom substrates (SMSs) of Lentinula edodes and Hypsizygus marmoreus on the resistance of rice leaves to Pyricularia oryzae infection. The spraying of the SMS extracts clearly suppressed the development of lesions caused by Py. oryzae infection. The accumulation of phytoalexins momilactones A and B, oryzalexin A, and sakuranetin was markedly induced by the spraying of extracts. The enhanced expression of defense related genes PR1b and PBZ was also found in leaves sprayed with the extracts. Treatments with the extracts also affected phytohormone levels. The levels of N(6)-(Δ(2)-isopentenyl)adenine and trans-zeatin markedly increased in response to treatment, whereas the levels of salicylic and jasmonic acids were largely unchanged.

We have previously shown that ONO-2952, a novel 18-kDa translocator protein (TSPO) antagonist, inhibits stress-induced accumulation of neurosteroids and noradrenaline release in the rat brain and alleviates the subsequent symptomatic responses with a brain TSPO occupancy of 50% or more. In this study, we measured ONO-2952 brain TSPO occupancy in conscious rhesus monkeys using positron emission tomography (PET) with 11C-PBR28 as ligand for translational research to clinical application. PET scans were performed after single and repeated oral administration of ONO-2952 at several dose levels for each animal, with sequential arterial blood sampling. In vitro binding studies showed that ONO-2952 potently binds to brain TSPO in monkeys with an affinity equivalent to that in rats. ONO-2952, given orally before PET scans, dose dependently decreased 11C-PBR28 uptake without marked brain region specificity. Results of the quantitative analysis using arterial input function revealed that TSPO occupancy after ONO-2952 single and repeated oral administration tended to increase in parallel with its plasma concentration, reaching the highest level of 100%. These findings indicate that ONO-2952 has sufficient brain distribution in primates and that ONO-2952 TSPO occupancy in humans can also be determined using PET.

The objective of this study was to investigate if there were any differences in survival and long-term outcomes between pediatric patients with and without neurological impairment who underwent tracheostomy.A retrospective chart review of pediatric patients (age 0-15 years) who underwent tracheostomy between March 2002 and December 2013 was conducted. Patients were categorized into two groups: those who were neurologically impaired (NI) (pediatric cerebral performance category, 3-6) and those who were not neurologically impaired (NN) (pediatric cerebral performance category, 1-2). Survival rates and cumulative incidence of weaning from mechanical ventilation or decannulation were calculated using the Kaplan-Meier method.A total of 212 patients were included. Among them, 141 were categorized into NI group and 71 into NN group. Between the two groups, there were no significant differences in survival rates and cumulative incidence of weaning from mechanical ventilation. In total patients, one-year survival rate was 0.86 (95%CI 0.80-0.90) and five-year survival rate was 0.71 (0.62-0.78). One-year weaning rate was 0.58 (0.51-0.65) and five-year weaning rate was 0.66 (0.59-0.74). Decannulation rates were significantly lower in NI group than in NN group (p 0.001). One-year and five-year decannulation rates were 0.04 (0.01-0.09) and 0.17 (0.10-0.29), respectively, in NI group, and 0.20 (0.12-0.33) and 0.54 (0.40-0.69), respectively, in NN group.In children who underwent tracheostomy, the decannulation rate was lower in those with neurological impairment compared with that in those without neurological impairment. There were no significant differences in survival or ventilator weaning between the two groups.

Conclusion Auditory phenotypes of two children harboring prestin gene mutations were congenital or pre-lingual onset, moderate to profound, slowly progressive or non-progressive, and audiograms with either flat configuration or prominently elevated thresholds at middle and high frequencies. Objectives Despite the essential role of the prestin gene in hearing, only one mutation in two families and a missense variant in a family had been reported previously before our study reporting another family. The purpose of this study was to characterize auditory phenotypes in children recently found to harbor novel mutations in the prestin gene. Methods The subjects were two sisters with bilateral sensorineural hearing loss who were compound heterozygotes for c.209G > A (p.W70X) and c.390A > C (p.R130S) mutations in the prestin gene. Clinical history and auditory test results were collected and analyzed. Results Hearing loss was present from birth in the younger sister and occurred before 6 years of age in the elder sister. The degree of hearing loss was profound in the elder sister with little progression, and moderate in the younger sister with no progression. The audiogram of the elder sister showed prominently elevated thresholds at middle and high frequencies, while that of the younger sister demonstrated a flat configuration.

First branchial cleft anomalies constitute a rare entity with variable clinical presentations and anatomic findings. We describe a 14-month-old girl with a congenital cutaneous fistula running from a cutaneous opening in the left submandibular triangle through the submandibular gland and ending in the pharyngeal cavity. These features suggested type II first branchial cleft fistula with an extremely unusual path. Complete excision resulted in successful treatment without recurrence. Since the first branchial cleft fistula can originate anywhere along the salivary gland and can extend from this area, surgeons should maintain a high index of suspicion for anatomic variants of this rare condition.

Esophageal duplication cyst is the second most common type of duplication cyst in the alimentary tract (10–15%). However, most of these cysts occur in the mediastinal part of the esophagus and cervical esophageal duplication cyst is extremely rare. Only approximately 20 pediatric cases have been reported in the English literature. We report the case of an infant who had suffered from prolonged wheezing since birth and was finally diagnosed with esophageal duplication cyst by ultrasonography and CT examination. The cyst had a common muscular layer with the normal esophagus and mucosal stripping was performed.

We report a case of congenital thyroid teratoma that was diagnosed in fetal life and completely excised after birth. The histopathological diagnosis was immature teratoma. Recurrent nerve palsy was experienced after the complete excision, but hypothyroidism was not seen in this case. Thyroid teratoma at a neonatal age has a good prognosis when intensive respiratory care is properly administered after birth and complete excision is performed.

Background Waardenburg syndrome type 1 (WS1) can be distinguished from Waardenburg syndrome type 2 (WS2) by the presence of dystopia canthorum. About 96% of WS1 are due to PAX3 mutations, and SOX10 mutations have been reported in 15% of WS2. Case presentation This report describes a patient with WS1 who harbored a novel SOX10 nonsense mutation (c.652G > T, p.G218*) in exon 3 which is the penultimate exon. The patient had mild prodromal neurological symptoms that were followed by severe attacks of generalized seizures associated with delayed myelination of the brain. The immature myelination recovered later and the neurological symptoms could be improved. This is the first truncating mutation in exon 3 of SOX10 that is associated with neurological symptoms in Waardenburg syndrome. Previous studies reported that the neurological symptoms that associate with WS are congenital and irreversible. These findings suggest that the reversible neurological phenotype may be associated with the nonsense mutation in exon 3 of SOX10. Conclusions When patients of WS show mild prodromal neurological symptoms, the clinician should be aware of the possibility that severe attacks of generalized seizures may follow, which may be associated with the truncating mutation in exon 3 of SOX10. Electronic supplementary material The online version of this article (10.1186/s12887-018-1139-2) contains supplementary material, which is available to authorized users.

To investigate the visual impairment certification status in Japan. Observational cross-sectional study. We asked all welfare offices throughout Japan to submit data concerning age, sex, causative diseases, and visual impairment grades for newly certified visually impaired individuals aged ≥ 18 years in the fiscal year of 2015. The certification was based on criteria of the Act on Welfare of Physically Disabled Persons. In total, data were collected for 12,505 newly certified visually impaired individuals. The most common age group for these individuals was 80-89 years (29.6%), followed by 70-79 (26.3%) and 60-69 (17.3%) years. The most common causative disease was glaucoma (28.6%), followed by retinitis pigmentosa (14.0%), diabetic retinopathy (12.8%), and macular degeneration (8.0%). Glaucoma was the most common causative disease in both sexes (30.2% in men and 27.0% in women). The most common impairment grade was grade 2 (31.8%), followed by grades 5 (24.3%) and grade 1 (16.1%). The number of visually impaired individuals with underlying glaucoma had increased in comparison with the number in the most recent surveys (from fiscal years 2007 to 2009), whereas the number of individuals with underlying diabetic retinopathy and macular degeneration had decreased. To our knowledge, this is the first nation-wide complete enumeration survey of newly certified visually impaired individuals in Japan. These findings may contribute to administrative activities concerning medical welfare as well as educational activities for preventing visual impairment.

Rice plants accumulate various specialized metabolites, including phenylamides, in response to pathogen attack. We prepared 25 phenylamides, and developed a method of analyzing them by multiple reaction monitoring with liquid chromatography coupled with tandem mass spectrometry. We analyzed phenylamides in rice leaves infected with Cochliobolus miyabeanus and Xanthomonas oryzae. The phenylamides induced included benzoyltryptamine, cinnamoyl-, p-coumaroyl-, feruloyl-, and benzoylserotonins, cinnamoyl and benzoyltyramines, feruloylagmatine, and feruloylputrescine. Some of the phenylamides exhibited antimicrobial activity against C. miyabeanus and X. oryzae, indicating that they are phytoalexins. Treatment with jasmonic acid, salicylic acid, 6-benzylaminopurine, and ethephone also induced phenylamide accumulation. The compositions of the induced amides varied depending on the plant hormone used, and cinnamoyltryptamine, cinnamoylserotonin, and cinnamoyltyramine were not induced by the plant hormones. These findings suggest that several plant hormones and additional factors are involved in phenylamide accumulation in response to pathogen infection in rice. Rice plant accumulates phenylamides in response to infection, wounding and treatments with jasmonic acid, salycilic acid, cytokinin, and ethylene.

The evaluation and management of vertigo in children varies among institutional and medical specialties. The aim of this study was to describe the characteristics of vertigo in children presenting at a national pediatric center. Patients < 16 years old presenting with vertigo to the department of otolaryngology at a national center for child health and development from April 2004 to October 2009 were included (N = 77; 42 males and 35 females; average age, 8.7 ± 3.4 years) in this study. The most common diagnoses were vestibular migraine (VM; N = 21), benign paroxysmal vertigo (BPV; N =16), unilateral vestibulopathy (N = 12), and psychogenic vertigo (N = 8). Significant differences were observed in the frequency of the diagnoses between children aged older and younger than 7 years: BPV was most common in children < 7 years of age (p < 0.01) and VM was most common in ≥ 27 years of age (p < 0.05). Because obtaining adequate information from children for making a correct diagnosis is sometimes difficult, acquiring sufficient information from the parents is important. In addition, getting the parents to record the nystagmus during a vertigo attack with a digital camera or cellular phone can be useful because observing the nystagmus recorded on the video is helpful for making a diagnosis. Furthermore, the parents are participating in their child's care by attempting to record the attack, strengthening the relationship between the parents and the child. The incidence of psychogenic vertigo is low (less than 10%). Therefore, although physicians have recently tended to define the disorder as psychogenic when no objective abnormality is found in a patient, making a diagnosis of psychogenic vertigo is not recommended. Because vertigo can sometimes make a child anxious, delivering the correct diagnosis and treatment at the early stage is important for preventing anxiety in affected children.

Study objectives Poor or short sleep and the presence of snoring indicative of sleep-disordered breathing (SDB) have been associated with behavioral problems in school-aged children. We examined the relationship between SDB, sleep duration, obesity risk, and behavioral characteristics in Japanese elementary school students using a large-scale survey. Methods We conducted a cross-sectional study of children enrolled in all 46 public primary schools in Matsuyama city, Japan. The children's parents or guardians completed a questionnaire that covered sleep habits, presence of SDB risk, and behavioral characteristics. Results In total, 24 296 responses were received (90% response rate). After excluding incomplete responses, we analyzed complete datasets for 17 769 children. Mean sleep duration decreased with age, as did the prevalence of pediatric SDB. We found an increased risk for the presence of SDB and short sleep among overweight/obese children. With SDB or short sleep, we observed significantly increased odds of restless behaviors, fidgety behaviors, and poor concentration in school. Conclusions Shorter sleep duration was associated with increased risk of obesity, and in turn, obesity increased SDB risk. Both short sleep duration and SDB risk were significantly associated with behavioral problems in school.

Objectives/Hypothesis To investigate possible association of hearing loss and SLC26A4 mutations with the subgroups of enlarged vestibular aqueduct (EVA) morphology in Japanese subjects with hearing loss. Study Design Retrospective multicenter study. Methods Forty-seven subjects who had vestibular aqueduct with midpoint diameter >1 mm by computed tomography of the temporal bone were enrolled at multiple sites across Japan, and DNA samples and clinical data were collected. EVA morphology was classified into four subgroups by the pattern of enlargement: aperture, aperture and midpoint, midpoint, and borderline enlargement. Venous blood DNA samples were subjected to polymerase chain reaction–based direct sequencing of all exons and exon–intron boundaries of the SLC26A4. Results Four novel SLC26A4 mutations were identified in the present study. SLC26A4 mutations were detected in almost all subjects with aperture, aperture and midpoint, and midpoint enlargement. In contrast, 71% of subjects with borderline enlargement had no SLC26A4 mutation. No significant difference was found in the distribution of truncating and nontruncating SLC26A4 mutations between the EVA subgroups. In addition, no significant correlation was observed between the EVA subgroups and hearing levels, incidence of hearing fluctuation, or progression of hearing loss. Conclusions Subgroups of EVA morphology were significantly correlated with the presence or absence of SLC26A4 mutation. In a subgroup analysis of subjects with SLC26A4 mutations, however, differences in the EVA subgroups were not correlated with SLC26A4 genotypes or characteristics of hearing loss. Level of Evidence NA. Laryngoscope, 124:E134–E140, 2014

Gorham-Stout syndrome is a rare disorder characterized by progressive osteolysis that leads to the disappearance of bone. Lymphvascular proliferation causes the local destruction of bony tissue. Owing to the low incidence of this syndrome, little is known about its etiology or treatment. We present an 11-year-old girl with Gorham-Stout syndrome that involved right petrous apex in temporal bone and upper clivus, which cause intracranial pressure increase and cerebrospinal fluid (CSF) leakage. The patient required surgical repair of CSF leakage by extradural middle fossa approach with temporal fascia flap. Combined treatment with interferon and propranolol prevented the progression of osteolysis.