Prevalence and factors of sleep problems among Japanese children: a population-based study.

Background: High prevalence of sleep problems in not only children with neurodevelopmental disorders (NDS) but also non NDS has been established. However, there are few studies that have looked into population-based and age-specific prevalence of sleep problems of children. Moreover, there are even fewer studies that have investigated the correlation of demographic and lifestyle-related factors affecting sleep problems in children. Considering these, the purpose of this study is to assess the correlation of the prevalence of sleep problems and selected socio-demographic and lifestyle-related factors in 5-year-old Japanese children in population-based study. Methods: Study children (SC) were recruited from two cohorts of the Hirosaki City 5-Year-Old Child Developmental Health Checkup Study. The first cohort consisted of 281 (162 males, 119 females) children recruited from 2014 to 2015, and the second cohort consisted of 2055 (1,068 males, 987 females) children from 2018 to 2019. In total there were 2,336 SC participants (1,230 males and 1,106 females). To determine the prevalence of sleep problems the Japanese Sleep Questionnaire for Preschoolers (JSQ-P) was utilized, and sleep problems are defined by a total score of ≥86. To determine socio-demographic and lifestyle-related factors affecting sleep, 10 factors (NDS diagnosis, birth month, childcare place, income, number of siblings, bedtime, waking time, sleeping hours, sleep onset delay, and screen time) were selected. Finally, to determine the correlation between prevalence of sleep problems and the selected demographic and lifestyle-related factors, data was analyzed using chi-square test. Results: The prevalence rate of sleep problems in 5-year-olds was 18% (369/2,055). Further, the prevalence of sleep problems was high in participants with ASD (50.4%), ADHD (39.8%), <2 million yen of income (30.5%), no siblings (24.2%), >22:00 of bedtime (30.7%), >7:30 of waking time (30.7%), <9 h of sleeping hours (25.3%), >30 min of sleep onset delay (35.3%), and ≥2 h of screen time (21.1%). Conclusion: The findings report 18% prevalence rate of sleep problems in 5-year-old children. Further, the findings establish a significant correlation of sleep problems and NDS, specific socio-demographic, and lifestyle-related factors. In considering the identified modifiable lifestyle-related factors contributing to sleep problems among the participants (i.e., bed/waking times and screen times), sleep programs to address these concerns are suggested.

Copy number variations in Japanese children with autism spectrum disorder.

OBJECTIVE: Although autism spectrum disorder (ASD) occurs worldwide, most genomic studies on ASD were performed on those of Western ancestry. We hypothesized ASD-related copy number variations (CNVs) of Japanese individuals might be different from those of Western individuals. METHODS: Subjects were recruited from the Hirosaki 5-year-old children's developmental health check-up (HFC) between 2013 and 2016 (ASD group; n = 68, control group; n = 124). This study conducted CNV analysis using genomic DNA from peripheral blood of 5-year-old Japanese children. Fisher's exact test was applied for profiling subjects and CNV loci. RESULTS: Four ASD-related CNVs: deletion at 12p11.1, duplications at 4q13.2, 8p23.1 and 18q12.3 were detected (P = 0.015, 0.024, 0.009, 0.004, respectively). Specifically, the odds ratio of duplication at 18q12.3 was highest among the 4 CNVs (odds ratio, 8.13). CONCLUSIONS: Four CNVs: microdeletion at 12p11.1, microduplications at 4q13.2, 8p23.1 and 18q12.3 were detected as ASD-related CNVs in Japanese children in this study. Although these CNVs were consistent with several reports by Western countries at cytoband levels, these did not consistent at detailed genomic positions and sizes. Our data indicate the possibility that these CNVs are characteristic of Japanese children with ASD. We conclude that Japanese individuals with ASD may harbor CNVs different from those of Western individuals with ASD.

Split notochord syndrome: ileal duplication causing intermittent episodes of vomiting.

Split notochord syndrome is a group of developmental abnormalities caused by abnormal splitting or deviation of the notochord, clinically resulting in the duplicated bowel associated with vertebral anomalies. In this syndrome, initial presentations due to duplicated bowel, vomiting, abdominal pain, and failure to thrive, usually occur before 1 year of age. We here report a 12-year-old boy with intermittent vomiting, previously diagnosed with cyclic vomiting syndrome. On abdominal x-ray examination, a defect in the closure of posterior vertebral arches was observed in the 5th lumbar vertebral body, indicating the complication of spina bifida occulta. This finding suggested the diagnosis of split notochord syndrome. A magnetic resonance imaging study revealed a cystic mass lesion in the pelvic cavity. (99m)Tc-pertechnetate scintigraphy, which is frequently used to detect ectopic gastric mucosa for the diagnosis of Meckel's diverticulum, showed a positive spot corresponding to the cystic mass lesion. Surgical resection of the cystic mass lesion demonstrated ileal duplication with ectopic gastric mucosa. Surgical findings suggest that symptoms of the patient were due to ulceration, inflammation, or bleeding caused by acid-peptic juice secreted from ectopic gastric mucosa. Duplication of the alimentary tract should be considered as a possible cause in patients with symptoms suggesting cyclic vomiting syndrome.

Pulse methylprednisolone therapy in type 3 adenovirus pneumonia with hypercytokinemia.

Adenovirus pneumonia is uncommon but its severe infection has a mortality as high as 10%, and survivors may have residual airway damages, manifested by bronchiectasis, bronchiolitis obliterans, or pulmonary fibrosis. We report a case of adenovirus pneumonia demonstrating fatal respiratory distress. Adenovirus was isolated from pharyngeal specimens using cell culture and typed as serotype 3 by a combination of polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis. The patient characteristically showed hypercytokinemia, characterized by increased levels of lactate dehydrogenase, ferritin, and several cytokines including interferon-gamma and interleukin-6. We treated the patient with pulse methylprednisolne therapy (25 mg/kg/day, for 3 days), resulting in the rapid amelioration of respiratory distress. This is the first report describing the treatment of pulse methylprednisolone therapy in fatal adenovirus pneumonia. During the clinical course, serum Krebs von den Lungen-6 (KL-6), which is a marker for the activity of diffuse interstitial lung disease, was elevated, suggesting that serum KL-6 could be available as a marker of pulmonary prognosis in viral pneumonia.

Acid sphingomyelinase: relation of 93lysine residue on the ratio of intracellular to secreted enzyme activity.

Acid sphingomyelinase (ASM) is the lysosomal enzyme responsible for the hydrolysis of sphingomyelin to ceramide and phosphocholine. An inherited deficiency of this enzymatic activity results in the Type A and B forms of Niemann-Pick disease (NPD). ASM is also readily secreted from cultured cells and can rapidly move from lysosomes to the cell surface upon stimulation by cytokines and other factors. Recent interest has focused on the role of this secreted/cell surface enzyme in ceramide-mediated signal transduction. We therefore sought to understand the mechanism(s) that might regulate intracellular targeting and secretion of this important hydrolase. Most lysosomal proteins are targeted to lysosomes in mammalian cells via the mannose 6-phosphate recognition system. Using cultured skin fibroblasts from I-cell disease patients, in which one of the enzymes responsible for mannose phosphorylation, GlcNAc-phosphotransferase, is deficient, we determined ASM activities in cell homogenates and media. The ratio of secreted to intracellular activity was approximately 8-fold greater in I-cell than in normal cells, indicating that mannose phosphorylation is important in the trafficking of this hydrolase. Most of the secreted activity required Zn+2 for full activity, supporting the concept that intracellular exposure of ASM to zinc within lysosomes is required for enzymatic activation. The recognition of lysosomal proteins by GlcNAc-phosphotransferase is mediated by protein structure, and a specific three-dimensional arrangement of lysine residues exposed on the surface of several enzymes has been shown to be critical for mannose phosphorylation. Alanine scanning mutagenesis of thirteen lysine residues in ASM demonstrated that 93lysine residue plays a critical role in ASM targeting since the K93A mutant had reduced intracellular activity, but enhanced secreted activity that was zinc responsive.

Renovascular hypertension due to antithrombin deficiency in childhood.

Inherited antithrombin deficiency generally causes a predisposition toward vascular thrombus above the age of 15 years. A 1-year-old boy developed renal hypertension caused by renal artery obstruction due to thrombus formation. This thrombus formation was attributed to antithrombin deficiency caused by a novel SERPINCI gene mutation (AT III Akita, M352R). This suggests that antithrombin deficiency can cause renal artery obstruction, inducing renal hypertension through vascular thrombosis even in children.

Signaling pathway for radiation-induced apoptosis in the lymphoblasts from neuronopathic (type A) and non-neuronopathic (type B) forms of Niemann-Pick disease.

Deficient activity of human lysosomal hydrolase, acid sphingomyelinase (ASM), results in the neuronopathic (type A) and non-neuronopathic (type B) forms of Niemann-Pick disease (NPD). A deficiency of ASM is known to deprive lymphoblasts of their response to apoptotic induction by X-ray irradiation. To elucidate the genetic heterogeneity of apoptotic induction in NPD cells, we investigated radiation-induced apoptosis of lymphoblasts in patients with type A (genotype: IVS3-2A-G/IVS3-2A-G) and type B (genotype: S436R/S436R) NPD. Epstein-Barr virus (EBV)-transformed lymphoblasts established from a patient with type A NPD, a patient with type B NPD and a normal control were irradiated with 20 Gy and incubated for 24 h. The cells were harvested and the morphological features of apoptosis were observed with DNA-specific fluorochrome bis-benzimide. Exposure of lymphoblasts to 20 Gy of radiation resulted in 25-30% apoptosis of total cells in normal lymphoblasts, 8-9% apoptosis in type A NPD and 20-27% apoptosis in type B NPD. The radiation-induced apoptotic response in the lymphoblasts of type A NPD was significantly different from that of the normal lymphoblasts (P<0.0005). On the other hand, the radiation-induced apoptotic response in type B NPD was not markedly different from that in normal lymphoblasts (P=0.624). In the patient with type B NPD, the signaling pathway for radiation-induced apoptosis was preserved in lymphoblasts, which suggests that the extent of cell signaling system disturbance due to ASM deficiency may be related to the phenotypes in types A and B NPD.