Inadequate sleep as a contributor to impaired glucose tolerance: A cross-sectional study in children, adolescents, and young adults with circadian rhythm sleep-wake disorder.

BACKGROUND: Sleep deprivation and circadian disruption are associated with decreased insulin sensitivity and hyperglycemia. It is uncertain whether circadian sleep-wake disorder (CRSWD), which relates to both the homeostatic sleep system and the circadian timing system, affects glycemic regulation and insulin secretion. We aimed to examine the associations among sleep duration, sleep architecture or circadian rhythm of the sleep-wake cycle, and glucose metabolism in children, adolescents, and young adults with CRSWD. METHODS: This cross-sectional observational study of 124 patients with CRSWD took place at Hyogo Children's Sleep and Development Medical Research Center in Hyogo, Japan. The patients underwent a 3-hour oral glucose tolerance test, anthropometric measurements, sleep-log analyses, and polysomnography. Analysis of covariance models were used to assess the association between sleep architecture or circadian rhythm of sleep-wake cycle and glucose/insulin homeostasis, adjusted for confounding variables such as age, gender, standardized body mass index, and sleep apnea index. RESULTS: Impaired glucose tolerance was detected in 25.8% of all patients with CRSWD. After adjustment for confounding variables, we found a negative association between total sleep time (TST) and the 2-hour plasma glucose level. Stage N1 (%TST) was also a significant predictor of 3-hour glucose level. However, we did not detect an association between circadian rhythm of the sleep-wake cycle and glucose/insulin measures. CONCLUSIONS: Decreased sleep duration and increased stage N1 (%TST) were associated with hyperglycemia in patients with CRSWD. Further research should elucidate how circadian misalignment in patients with CRSWD is associated with glucose and insulin homeostasis.

Variations in early gross motor milestones and in the age of walking in Japanese children.

BACKGROUND: Gross motor development is usually assessed in terms of age of achievement of motor milestones. Although there is generally an impression of faster development if the milestones are achieved at younger ages, no longitudinal studies have been done on the associations between the milestones, especially in Japan. As a part of the Japan Children's Study, the purpose of the present study was to determine whether the achievement of gross motor milestones in infancy is related with the age of walking. METHODS: This was a prospective cohort study of 290 healthy and term infants born in a district of Osaka City, Japan. Three milestones (rolling over, sitting, and crawling) were observed in the laboratory for infants aged at 4 and 9 months by a pediatrician and a developmental psychologist, and the age of walking was confirmed in questionnaires filled in by the parents at 18 and 27 months. RESULTS: Children who could roll over at 4 months, and sit and crawl at 9 months, walked earlier than children who could not roll over, sit and crawl, respectively. With regard to crawling, children who were creeping had a 1 month delay in walking, and those who could not move forward had a 2 month delay compared to typical crawlers. On multiple regression analysis these three milestones were positively associated with walking: rolling over (ß= 0.567), sitting (ß= 1.973) and crawling (ß= 1.473). CONCLUSION: The age and the patterns of sitting, crawling and rolling over were all related to the age of independent walking among Japanese infants. Consideration of milestone definition and variations is essential in medical check-up.

Head growth evaluation in early childhood, from the Japan Children's Study.

BACKGROUND: Head circumference (HC) trajectories are held to reflect neurological development and the acquirement of intelligence. It is important to assess HC growth accurately because atypical HC growth is an indicator of various developmental disorders. HC growth is determined by both familial and physical factors but, hitherto, no one has considered both factors together. The aim of the present study was thus to investigate the relationship between HC, physical growth, and parental HC. METHODS: The study group in the Japan Children's Study consisted of 192 healthy full-term Japanese children. HC (maximum occiptofrontal circumference), height and bodyweight were measured at the ages of 4, 9 and 18 months. Multiple regression analysis were conducted predicting the HC from the body measurements and mid-parental HC (defined as the average of standardized paternal and maternal HC). RESULTS: Adjusted multiple R(2) were 0.336, 0.307 and 0.259, measured at the aforementioned three stages. Bodyweight and mid-parental HC predicted the HC on each occasion (P < 0.01). Bodyweight was more relevant than mid-parental HC. CONCLUSIONS: HC growth is influenced by physical growth and parental HC; therefore, it is important to consider both physical and familial factors. A formula is herein proposed to assess HC using bodyweight and mid-parental HC.

[Laterality of upper extremity movements in infancy: observations at 4 and 9 months of age].

This study investigated the process involved in the lateralization of movements during infancy by observing upper extremity movements in a laboratory setting. Reaching for flying rings, balls, mini toy cars, and small round cookies were observed and recorded by videotape at 4 and 9 months of age. The subjects were 202 infants who participated in Japan Children's Study, a cohort study on the development of sociability. Infants reached for objects significantly more frequently at 9 months (98%) than at 4 months (40%) (p<0.001). Though the lateral preference in reaching for balls at 4 months was ambiguous, reaching for toy cars was performed more frequently with the right hand at 9 months (50%) than with the left one (19%) (p<0.01). Lateralization of the upper extremity movements is thought to appear by 9 months.

An Interactive Smartphone App, Nenne Navi, for Improving Children's Sleep: Pilot Usability Study.

BACKGROUND: Healthy sleep is important not only for physical health but also for brain development in children. Several reports have revealed that Japanese adults and children have later bedtimes and shorter sleep durations compared with those in other countries, possibly because of Japanese culture and lifestyles. Therefore, an intervention tool that is suitable to the Japanese sociocultural environment is urgently needed to improve children's sleep problems in their early years. OBJECTIVE: To provide appropriate sleep health literacy to caregivers and change their parenting behavior, we developed a smartphone app that allows reciprocal interaction between caregivers and pediatric sleep experts. This paper describes a preliminary study to examine the app's basic design and functions and to establish its acceptability and usability in a small sample. METHODS: A total of 10 caregivers and 10 infants (aged 18-28 months; 4/10, 40% boys) living in Japan participated in the study. At the start of the trial, the e-learning content regarding sleep health literacy was delivered via a smartphone. Thereafter, caregivers manually inputted recorded data about their own and their infant's sleep habits for 8 consecutive days per month for 2 months. After pediatric sleep experts retrieved this information from the Osaka University server, they specified the problems and provided multiple sleep habit improvement suggestions to caregivers. Caregivers then selected one of the feasible pieces of advice to practice and reported their child's sleep-related behaviors via the app. Actigraphy was used to monitor children's sleep behaviors objectively. The concordance between the information provided by caregivers and the actigraphy data was assessed. The acceptability and usability of the app were evaluated using self-report questionnaires completed by caregivers; qualitative feedback was obtained via semistructured interviews after the intervention. RESULTS: There was no significant difference between the information provided by the caregivers and the actigraphy data for bedtimes and wake-up times (P=.13 to P=.97). However, there was a difference between the actigraphy data and the caregivers' reports of nighttime sleep duration and nighttime awakenings (P<.001 each), similar to prior findings. User feedback showed that 6 and 5 of the 10 caregivers rated the app easy to understand and easy to continue to use, respectively. Additionally, 6 of the 10 caregivers rated the app's operativity as satisfactory. Although this was a short-term trial, children's sleep habits, caregivers' sleep health consciousness, and parenting behaviors improved to some extent. CONCLUSIONS: The present findings suggest that the app can easily be used and is acceptable by Japanese caregivers. Given the user feedback, the app has the potential to improve children's sleep habits by sending individualized advice that fits families' backgrounds and home lives. Further studies are needed to confirm the efficacy of the app and facilitate social implementation.

High incidence of meropenem resistance among alpha-hemolytic streptococci in children with cancer.

BACKGROUND: Infections caused by antibiotics-resistant Gram-positive bacteria have been reported from many pediatric hematology-oncology centers. METHODS: The susceptibility profiles to meropenem, piperacillin, and vancomycin among oral flora isolates of alpha-hemolytic streptococci (AHS) obtained from six children with cancer who received several empirical therapies (ET) against febrile neutropenia, were investigated. RESULTS: Meropenem minimum inhibitory concentration (MIC) of AHS isolated from ET patients was 2.167 +/- 0.258 microg/mL (mean +/- SD), which was significantly higher than the MIC of AHS isolated from control groups. Intriguingly, AHS isolated approximately 6 months after hospital discharge indicated recovery of susceptibility to meropenem. CONCLUSIONS: AHS isolates from neutropenic children with cancer should be checked for antibiotic susceptibility, even against carbapenems.

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.

STI571 inhibits growth and adhesion of human mast cells in culture.

Stem cell factor (SCF)/c-kit system is critical for human mast cell development. We thus examined the effects of STI571, an inhibitor of the c-kit tyrosine kinase receptor, on the proliferation and function of human mast cells. STI571 at concentrations of 10(-6) M or higher almost completely abolished the SCF-dependent progeny generation from cord blood-derived cultured mast cells through an inhibition of the tyrosine phosphorylation of c-kit. The compound also suppressed the early phase of mast cell development. The extinction of mast cell growth induced by STI571 may be due largely to apoptosis according to the flow cytometric analysis and gel electrophoresis. Two-hour exposure to STI571 that failed to influence the total viable cell number suppressed adhesion of the cells to fibronectin in the presence of SCF without altering the expressions of integrin molecules. Our results may provide a fundamental insight for the clinical application of STI571 in allergic disorders.

Increase in incidence of elderly-onset patients with myasthenia gravis in Nagano Prefecture, Japan.

OBJECTIVES: In European countries and the United States the incidence of elderly-onset myasthenia gravis (MG) has recently been increasing. To investigate whether the incidence of the elderly-onset MG has increased in Nagano Prefecture of Japan, we divided the patients into young and elderly groups, and retrospectively examined their incidence. PATIENTS AND METHODS: On the basis of two-step questionnaires sent to hospitals and the patient list of the intractable disease registration system in Nagano Prefecture we studied 213 MG patients diagnosed between 1982 and 2001. This 20-year period was divided into 4 five-year terms, and the incidence of MG in young- (younger than 65) and elderly-onset (65 or older) groups was investigated separately for each term. RESULTS: The ratio of the elderly-onset group showed a significantly positive correlation with terms irrespective of associated thymoma (r=0.98, p<0.05). There was a significant difference in the mean onset age among the 4 terms (p<0.005). The standardized incidence of MG gradually increased in both young- and elderly-onset groups as well as in the whole age range. The elderly group showed a particularly high incidence in females (12.01/million/year) and in patients without thymoma (8.78/million/year) in the final five years. CONCLUSIONS: We confirmed that the incidence of elderly-onset MG has recently been increasing in the Nagano Prefecture. Since the change of the age distribution in this district is almost identical to that of the whole country, the incidence of MG might have been increasing in Japan as a whole, particularly in the elderly population.

IL-9 enhances the growth of human mast cell progenitors under stimulation with stem cell factor.

We examined the effects of IL-9 on human mast cell development from CD34(+) cord blood (CB) and peripheral blood cells in serum-deprived cultures. IL-9 apparently enhanced cell production under stimulation with stem cell factor (SCF) from CD34(+) CB cells. A great majority of the cultured cells grown with SCF + IL-9 became positive for tryptase at 4 wk. In methylcellulose cultures of CD34(+) CB cells, IL-9 increased both the number and size of mast cell colonies grown with SCF. Furthermore, SCF + IL-9 caused an exclusive expansion of mast cell colony-forming cells in a 2-wk liquid culture of CD34(+) CB cells, at a level markedly greater than for SCF alone. Clonal cell cultures and RT-PCR analysis showed that the targets of SCF + IL-9 were the CD34(+)CD38(+) CB cells rather than the CD34(+)CD38(-) CB cells. IL-9 neither augmented the SCF-dependent generation of progeny nor supported the survival of 6-wk-cultured mast cells. Moreover, there was no difference in the appearance of tryptase(+) cells and histamine content in the cultured cells between SCF and SCF + IL-9. The addition of IL-9 increased numbers of mast cell colonies grown with SCF from CD34(+) peripheral blood cells in children with or without asthma. It is of interest that mast cell progenitors of asthmatic patients responded to SCF + IL-9 to a greater extent than those of normal controls. Taken together, IL-9 appears to act as a potent enhancer for the SCF-dependent growth of mast cell progenitors in humans, particularly asthmatic patients.