Improving Children's Sleep Habits Using an Interactive Smartphone App: Community-Based Intervention Study.

BACKGROUND: Sleep problems are quite common among young children and are often a challenge for parents and a hinderance to children's development. Although behavioral therapy has proven effective in reducing sleep problems in children, a lack of access to professionals who can provide effective support is a major barrier for many caregivers. Therefore, pediatric sleep experts have begun developing apps and web-based services for caregivers. Despite the substantial influence of cultural and familial factors on children's sleep, little effort has gone into developing cultural or family-tailored interventions. OBJECTIVE: This study aimed to examine the effectiveness of the interactive smartphone app "Nenne Navi," which provides culturally and family-tailored suggestions for improving sleep habits in young Japanese children through community-based long-term trials. The study also aimed to investigate the association between app-driven improvements in sleep and mental development in children. METHODS: This study adopted a community-based approach to recruit individuals from the Higashi-Osaka city (Japan) who met ≥1 of the following eligibility criteria for sleep problems: sleeping after 10 PM, getting <9 hours of nighttime sleep, and experiencing frequent nighttime awakenings. A total of 87 Japanese caregivers with young children (mean 19.50, SD 0.70 months) were recruited and assigned to the app use group (intervention group) or the video-only group (control group). Both groups received educational video content regarding sleep health literacy. The caregivers in the intervention group used the app, which provides family-tailored suggestions, once per month for 1 year. RESULTS: A total of 92% (33/36) of the caregivers in the app use group completed 1 year of the intervention. The participants' overall evaluation of the app was positive. The wake-up time was advanced (base mean 8:06 AM; post mean 7:48 AM; F1,65=6.769; P=.01 and sleep onset latency was decreased (base mean 34.45 minutes; post mean 20.05 minutes; F1,65=23.219; P<.001) significantly in the app use group at the 13th month compared with the video-only group. Moreover, multiple regression analysis showed that decreased social jetlag (ß=-0.302; P=.03) and increased sleep onset latency SD (ß=.426; P=.02) in children predicted a significant enhancement in the development of social relationships with adults. At 6 months after the completion of the app use, all the caregivers reported continuation of the new lifestyle. CONCLUSIONS: The present findings suggest that the app "Nenne Navi" has high continuity in community use and can improve sleep habits in young Japanese children and that interventions for sleep habits of young children may lead to the enhancement of children's social development. Future studies must focus on the effectiveness of the app in other regions with different regional characteristics and neuroscientific investigations on how changes in sleep impact brain development.

Clasmatodendrosis is associated with dendritic spines and does not represent autophagic astrocyte death in influenza-associated encephalopathy.

BACKGROUND: Influenza-associated encephalopathy (IAE) is one of the most serious CNS complications of an influenza virus infection, with unclear pathophysiology. Clasmatodendrosis is a complex of morphological changes in astrocytes characterized by fragmentation of the distal processes and swollen cell bodies. Although pathologists in Japan have long been aware of the presence of clasmatodendrosis in IAE brains, no details of the phenomenon have been published to date. We aimed to confirm the existence, and characterize the spatial distribution of clasmatodendrosis in postmortem IAE brains. METHODS: Autopsied brains from 7 patients with IAE and 8 non-IAE subjects were examined immunohistochemically. In addition, immunofluorescent staining and electron microscopy were performed. RESULTS: Clasmatodendrosis was present in all examined regions of the IAE brains, but none of the control brains. Fragmented processes of astrocytes in IAE brains were closely adjacent to synapses on the dendritic spines, with the fragmentation especially prominent in the cerebellar molecular layer. In addition, the clasmatodendrotic astrocytes were negative for autophagy markers. Furthermore, whereas aquaporin 4 was predominantly detected in the perivascular endfeet of astrocytes in the control brains, its primary localization site shifted to the fragmented perisynaptic processes in the IAE brains. CONCLUSION: Clasmatodendrosis was distributed diffusely in the IAE brains in close association with synapses, and was not caused by astrocyte autophagy. Clasmatodendrosis may be a suggestive pathological feature of IAE.

Aberrant Cerebellar-Cerebral Functional Connectivity in Children and Adolescents With Autism Spectrum Disorder.

The cerebellum, which forms widespread functional networks with many areas in the cerebral cortices and subcortical structures, is one of the brain regions most consistently reported to exhibit neuropathological features in patients with autism spectrum disorder (ASD). However, cerebellar functional connectivity (FC) studies in patients with ASD have been very sparse. Using resting state functional connectivity (rsFC) analysis, we investigated the FC of the hemispheric/vermal subregions and the dentate nucleus of the cerebellum with the cerebral regions in 36 children and adolescents [16 participants with ASD, 20 typically developing (TD) participants, age: 6-15 years]. Furthermore, an independent larger sample population (42 participants with ASD, 88 TD participants, age: 6-15 years), extracted from the Autism Brain Imaging Data Exchange (ABIDE) II, was included for replication. The ASD group showed significantly increased or decreased FC between "hubs" in the cerebellum and cerebral cortices, when compared with the TD group. Findings of aberrant FCs converged on the posterior hemisphere, right dentate nucleus, and posterior inferior vermis of the cerebellum. Furthermore, these aberrant FCs were found to be related to motor, executive, and socio-communicative functions in children and adolescents with ASD when we examined correlations between FC and behavioral measurements. Results from the original dataset were partially replicated in the independent larger sample population. Our findings suggest that aberrant cerebellar-cerebral FC is associated with motor, socio-communicative, and executive functions in children and adolescents with ASD. These observations improve the current knowledge regarding the neural substrates that underlie the symptoms of ASD.

Japanese Sleep Questionnaire for Elementary Schoolers (JSQ-ES): validation and population-based score distribution.

OBJECTIVE: The Japanese Sleep Questionnaire for Elementary Schoolers (JSQ-ES) was developed to measure the sleep habits and disturbances of Japanese children. The current study aimed to present psychometric properties and describe the score distribution of the JSQ-ES. In addition, it examined correlations between the sleep and daytime behavior of school-aged children. METHOD: Guardians of 4369 elementary school children and 100 children diagnosed with sleep disorders in two clinics completed the JSQ-ES. RESULTS: Exploratory factor analysis and confirmatory factor analysis suggested a nine-factor structure. The JSQ-ES internal consistency was 0.876 and 0.907 for the community and clinical groups, respectively. Score distribution differences were observed between the two groups. A cut-off point of 80 was identified for the total JSQ-ES score. CONCLUSIONS: Exploratory factor analysis and confirmatory factor analysis suggested a nine-factor structure: (1) restless legs syndrome; (2) sleep-disordered breathing; (3) morning symptoms; (4) nighttime awakenings; (5) insomnia; (6) excessive daytime sleepiness; (7) daytime behavior; (8) sleep habits; and (9) irregular/delayed sleep phase. The study verified that the JSQ-ES is a valid and reliable instrument with which to evaluate Japanese sleep habits using a large population-based sample. The JSQ-ES may be useful in both clinical and academic settings.

White matter volume in the brainstem and inferior parietal lobule is related to motor performance in children with autism spectrum disorder: A voxel-based morphometry study.

Many studies have reported poor motor performance in autism spectrum disorder (ASD); however, the underlying brain mechanisms remain unclear. Recent neuroimaging studies have suggested that abnormalities of the white matter (WM) are related to the features of ASD. In this study, we used voxel-based morphometry (VBM) to investigate which WM regions correlate with motor performance in children with ASD, and whether the WM volume in those brain regions differed between children with ASD and typically developing (TD) children. The subjects included 19 children with ASD and 20 TD controls. Motor performance was assessed using the Movement Assessment Battery for Children 2 (M-ABC 2). Children with ASD showed poorer motor performance than did the controls. There was a significant positive correlation between the total test score on the M-ABC 2 and the volume of WM in the brainstem and WM adjacent to the left supramarginal gyrus (SMG). In addition, compared with the TD controls, children with ASD had a decreased volume of WM in the brainstem and adjacent to the left intraparietal sulcus, which is close to the SMG. These findings suggest that structural changes in the WM in the brainstem and left inferior parietal lobule may contribute to poor motor performance in children with ASD. Autism Res 2016, 9: 981-992. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Sleep problems are more frequent and associated with problematic behaviors in preschoolers with autism spectrum disorder.

BACKGROUND: Children with autism spectrum disorder (ASD) often suffer from sleep problems that in turn correlate with behavioral problems. However, in Japan, there have been few studies of sleep problems in children with ASD. AIMS: This study compared sleep problems in preschoolers from the community and preschoolers with ASD in Japan, and examined whether sleep problems were related to problematic behaviors in ASD preschoolers. METHODS AND PROCEDURES: Sleep problems were assessed in 965 community and 193 ASD preschoolers using the Japanese Sleep Questionnaire for Preschoolers, which was developed to assess sleep problems in Japanese preschoolers. Behavioral problems were assessed in 107 ASD preschoolers using the Child Behavior Checklist. OUTCOMES AND RESULTS: Compared with community preschoolers, ASD preschoolers experienced significantly more sleep problems, including obstructive sleep apnea and parasomnias. ASD preschoolers with sleep problems exhibited more behavioral problems than those without sleep problems. The severity of sleep problems, especially insomnia, was significantly correlated with behavioral problems in ASD preschoolers. CONCLUSIONS AND IMPLICATIONS: The present study suggests that sleep problems, especially obstructive sleep apnea, are more common in ASD preschoolers than in community preschoolers. The study also shows that sleep problems, especially insomnia, are related to problematic behavior in ASD preschoolers.

Prolonged elevation of serum neuron-specific enolase in children after clinical diagnosis of brain death.

To elucidate the time course of neuronal cell death after the clinical criteria for brain death are met, the authors reviewed serial changes of serum neuron-specific enolase levels in 3 children (age range, 3-15 years) clinically diagnosed as brain dead due to cardiopulmonary arrest. All patients survived for more than 2 months after brain death. Children with brain death had higher peak neuron-specific enolase values (1069-2849 ng/mL) than did 3 control children (256-1800 ng/mL) who did not become brain dead but had poor neurological outcome (1 death, 2 vegetative state) after cardiopulmonary arrest. A major finding is that children with brain death showed persistent elevation of neuron-specific enolase at 4 weeks (>400 ng/mL) and 8 weeks (>50 ng/mL) after cardiopulmonary arrest, in comparison with 2 surviving patients without brain death (<50 ng/mL at 4 weeks). This prolonged elevation of neuron-specific enolase suggests that total brain necrosis might not be present at the time of clinical diagnosis of brain death.

Hematopoietic stem cell transplantation with reduced intensity conditioning from a family haploidentical donor in an infant with familial hemophagocytic lymphohistocytosis.

Allogeneic hematopoietic stem cell transplantation is the only curative method for patients with familial hemophagocytic lymphohistiocytosis (FHL). We present a case of a 3-month-old girl with Munc13-4 mutation (FHL3), who underwent bone marrow transplantation (BMT) from her human leukocyte antigen-haploidentical mother following reduced intensity conditioning (RIC) with fludarabine, melphalan, and busulfan. Engraftment after BMT was generally uneventful, with only mild acute graft versus host disease. Munc13-4 protein was restored following BMT, and she is well and free of disease 14 months after BMT. These results suggest that BMT with RIC from a family haploidentical donor may sufficiently restore immune regulation in infants, while lessening treatment-related mortality and long-term sequelae.