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BackgroundHigh 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.MethodsStudy 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.ResultsThe 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%), 22:00 of bedtime (30.7%), >7:30 of waking time (30.7%), 30 min of sleep onset delay (35.3%), and ≥2 h of screen time (21.1%).ConclusionThe 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.

Despite the pivotal role of developmental surveillance in pediatric practice for the early detection of neurodevelopmental disorders (NDDs), there are several barriers, including scarcity of time and staff availability, to its implementation. Additionally, inadequate parental knowledge on what to expect about their child's development contributes to potential delays in the early identification of NDDs. Home-based records (HBRs) are widely used in both high-income and low- and middle-income countries, allowing caregivers to prospectively chart the child's development, including milestone attainment, and thus can be a useful tool for developmental surveillance. Therefore, we analyzed data on milestone attainment from birth to 5 years of age obtained through the home-based records (the Maternal Child Health Handbook: MCHH) in 720 children who attended the Hirosaki Five-year-old children Developmental Health Check-up Study in Hirosaki, Japan to identify trajectory patterns of milestone attainment. Parallel process latent class growth analysis on four milestone domains (motor, social interaction, communication, and self-care) revealed three different trajectories (Class 1: “Consistent milestone attainment” group; 42%, Class 2: “subtle initial delay and catch-up” group; 45%, Class 3: “Consistent failure to attain expected milestones” group; 13%). In Class 3, 90% of children were diagnosed with at least one NDDs at age 5 and approximately 65% of children had autism spectrum disorder and/or intellectual disability, the rate of which was higher than that in the other two classes. Boys and preterm-born children were more likely to be assigned to classes with less favorable trajectories of milestone attainment. Although the use of the MCHH alone does not substitute diagnostic evaluation for NDDs, our study findings suggest the potential utility of the MCHH as a tool to educate parents on what longitudinal patterns of milestone attainment are concerning and require prompt visits to professionals.

Abstract Background Xylitol is an approved food additive that is widely used as a sweetener in many manufactured products. It is also used in pharmaceuticals. Secondary oxalosis resulting from high dietary oxalate has been reported. However, reported cases of oxalosis following xylitol infusion are rare. Case presentation A 39-year-old man with a 16-year history of organic psychiatric disorder was hospitalized for a laparoscopic cholecystectomy because of cholecystolithiasis. He had been treated with several antipsychotics and mood stabilizers, including lithium. The patient had polyuria (> 4000 mL/day) and his serum sodium levels ranged from 150 to 160 mmol/L. Urine osmolality was 141 mOsm/L, while serum arginine vasopressin level was 6.4 pg/mL. The patient was diagnosed with nephrogenic diabetes insipidus (NDI), and lithium was gradually discontinued. Postoperative urine volumes increased further to a maximum of 10,000 mL/day, and up to 10,000 mL/day of 5% xylitol was administered. The patient’s consciousness level declined and serum creatinine increased to 4.74 mg/dL. This was followed by coma and metabolic acidosis. After continuous venous hemodiafiltration, serum sodium improved to the upper 140 mmol/L range and serum creatinine decreased to 1.25 mg/dL at discharge. However, polyuria and polydipsia of approximately 4000 mL/day persisted. Renal biopsy showed oxalate crystals and decreased expression of aquaporin-2 (AQP2) in the renal tubules. Urinary AQP2 was undetected. The patient was discharged on day 82 after admission. Conclusions Our patient was diagnosed with lithium-induced NDI and secondary oxalosis induced by excess xylitol infusion. NDI became apparent perioperatively because of fasting, and an overdose of xylitol infusion led to cerebrorenal oxalosis. Our patient received a maximum xylitol dose of 500 g/day and a total dose of 2925 g. Patients receiving lithium therapy must be closely monitored during the perioperative period, and rehydration therapy using xylitol infusion should be avoided in such cases.

Abstract Backgrounds Whether there is a true increase in autism spectrum disorder (ASD) frequency or not remains unclear. Additionally, the rates of co-existing neurodevelopmental disorders (NDD) in a total population sample has not been fully examined before. Therefore, using a total population sample in Japan, we aimed to estimate the prevalence and cumulative incidence of autism spectrum disorder (ASD) annually, to determine whether there is a true increase in ASD prevalence by estimating the cumulative incidence of ASD annually, and to examine the rates of co-existing neurodevelopmental disorders (NDD). Method In this cross-sectional sequential design study, all 5-year-old children in the catchment area underwent the screening annually from the year 2013–2016. Screen-positive children were invited to participate in a comprehensive assessment, including child and parent interview, behavioral observation, and cognitive and motor function testing. All cases were reviewed by a multidisciplinary research team. Results Caregivers of 3954 children returned the screening, among which 559 children underwent the assessment with 87 children receiving an ASD diagnosis. Adjusted ASD prevalence was 3.22% (95% confidence interval (CI) 2.66–3.76%). The male to female ratio of the crude prevalence was 2.2:1. The cumulative incidence of ASD up to 5 years of age for the total study years was 1.31% (95% CI 1.00–1.62%). A generalized linear model revealed no significant linear trends in 5-year cumulative incidence over the study years. Only 11.5% of children had ASD alone; the remaining 88.5% were found to have at least one co-existing NDD. Limitations Modest sample size for a total population study. Conclusions Our findings demonstrate the stability of the 5-year cumulative incidence of ASD, implying no true rise in ASD incident cases over the 4-year study period in the study catchment area. High rates of co-existing NDDs reflect the importance of investigating broad developmental challenges in children with ASD.

Social capital is an important factor that affects mental health. The purpose of this study was to examine the relationship between social capital and depression and between social capital and quality of life (QoL) in children in elementary and junior high school and to examine how this relationship differs in relevant patterns at both the individual- and school-level. The study was conducted in all elementary and junior high schools in a single municipality; the subjects consisted of 3,722 elementary school and 3,987 junior high school students (aged from 9 to 15). A multilevel linear mixed effect model analysis revealed that all three subscales of social capital were associated with depression and QoL at the individual-level: The school social capital at the individual-level showed the strongest association with depression and QoL. We also found that some of social capital at the school-level was associated with depression and QoL. An interactive effect was observed between educational stage (elementary and junior high) and some of social capital subscales. Specifically, the inverse association between school social capital and depression was stronger among the junior high students, while the positive association between school and neighborhood social capital and QoL was stronger among the elementary students. These interactions suggest that social capital impacts depression and QoL differently in elementary and junior high students. These findings suggest that the degree of association of social capital domains differs in mental health among the educational stage.

The central symptom of autism spectrum disorder (ASD) is deficiency in social communication, which is generally viewed as being caused by pragmatic impairment (PI). PI is difficulty in using language appropriately in social situations. Studies have confirmed that PI is the result of neurological, cognitive, linguistic, and sensorimotor dysfunctions involving intricately intertwined factors. To elucidate the whole picture of this impairment, an approach from a multifaceted perspective fusing those factors is necessary. To this end, comprehensive PI mapping is a must, since no comprehensive mapping has yet been developed. The aim of this research is to present a model of annotation scheme development and corpus construction to efficiently visualize and quantify for statistical investigation occurrences of PI, which enables comprehensive mapping of PI in the spoken language of Japanese ASD individuals. We constructed system networks (lexicogrammatical option systems speakers make choices from) in the theoretical framework of Systemic Functional Linguistics, from which we developed an annotation scheme to comprehensively cover PI. Since system network covers all possible lexicogrammatical choices in linguistic interaction, it enables a comprehensive view of where and in what lexicogrammar PI occurs. Based on this annotation scheme, we successfully developed the Corpus of ASD + Typically Developed Spoken Language consisting of texts from 1,187 audiotaped tasks performed by 186 ASD and 106 typically developed subjects, accommodating approximately 1.07 million morphemes. Moreover, we were successful in the automatization of the annotation process by machine learning, accomplishing a 90 percent precision rate. We exemplified the mapping procedure with a focus on the spoken use of negotiating particles. Our model corpus is applicable to any language by incorporating our method of constructing the annotation scheme, and would give impetus to defining PI from a cross-linguistic point of view, which is needed because PI of ASD reflects cross-linguistic differences.

Abstract Objective Type 2 diabetes mellitus (T2DM) is associated with a high prevalence of depression, which is influenced by personality traits and coping style. However, these psychological factors have not been well studied in individuals with T2DM. The association between coping behaviors and the reported levels of depressive symptoms was examined in individuals with T2DM. Methods The subjects were 435 T2DM patients (mean age 63.1 ± 12.6 years). Depressive status, personality traits and coping behaviors were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Brief Scale for Coping Profile (BSCP). Lifestyle factors and glycated hemoglobin A1c (HbA1c) levels in the patients were also included in the analyses. Results Among the 435 subjects with T2DM, 130 (29.9%) exhibited possible depression, and 68 (15.6%) displayed probable depression. After adjustment for confounders, logistic and multiple regression analyses revealed that certain coping profile scores, such as Changing one’s point of view, Emotional expression involving others and Avoidance and suppression, were consistently and significantly associated with the presence and severity of depression. No relationship was found between depression and HbA1c. Conclusion These findings indicate that Maladaptive emotion-focused coping strategies, such as Emotional expression involving others and Avoidance and suppression, are protective factors and that Adaptive emotion-focused coping, such as Changing one’s point of view, is a risk factor for depression in T2DM patients. Psychological intervention focusing on the coping profile may reduce depressive symptoms. Additional studies are needed to examine the relationships between psychological factors and depressive symptoms using a longitudinal study design.

Background: Abnormalities of lipid metabolism contributing to the autism spectrum disorder (ASD) pathogenesis have been suggested, but the mechanisms are not fully understood. We aimed to characterize the lipid metabolism in ASD and to explore a biomarker for clinical evaluation. Methods: An age-matched case-control study was designed. Lipidomics was conducted using the plasma samples from 30 children with ASD compared to 30 typical developmental control (TD) children. Large-scale lipoprotein analyses were also conducted using the serum samples from 152 children with ASD compared to 122 TD children. Data comparing ASD to TD subjects were evaluated using univariate (Mann-Whitney test) and multivariate analyses (conditional logistic regression analysis) for main analyses using cofounders (diagnosis, sex, age, height, weight, and BMI), Spearman rank correlation coefficient, and discriminant analyses. Findings: Forty-eight significant metabolites involved in lipid biosynthesis and metabolism, oxidative stress, and synaptic function were identified in the plasma of ASD children by lipidomics. Among these, increased fatty acids (FAs), such as omega-3 (n-3) and omega-6 (n-6), showed correlations with clinical social interaction score and ASD diagnosis. Specific reductions of very-low-density lipoprotein (VLDL) and apoprotein B (APOB) in serum of ASD children also were found by large-scale lipoprotein analysis. VLDL-specific reduction in ASD was correlated with APOB, indicating VLDL-specific dyslipidaemia associated with APOB in ASD children. Interpretation: Our results demonstrated that the increases in FAs correlated positively with social interaction are due to VLDL-specific degradation, providing novel insights into the lipid metabolism underlying ASD pathophysiology. Funding: This study was supported mainly by MEXT, Japan.

BackgroundDespite their importance in population health among children and adolescents, our understanding of how individual items mutually interact within and between pediatric health-related quality of life (HRQOL) and school social capital is limited.MethodsWe employed network analysis in a general population sample of 7759 children aged 9-15 years to explore the network structure of relations among pediatric HRQOL and school social capital items measured using validated scales. Furthermore, network centrality was examined to identify central items that had stronger and more direct connections with other items in the network than others. Network structure and overall strength of connectivity among items were compared between groups (by sex and age).ResultsOur analysis revealed that the item related to school/academic functioning and the item related to shared enjoyment among students had the highest strength centrality in the network of HRQOL and school social capital, respectively, underpinning their critical roles in pediatric HRQOL and school social capital. Additionally, the edge connecting "I trust my friends at school" and "trouble getting along with peers" had the strongest negative edge weight among ones connecting school social capital and pediatric HRQOL constructs. Network comparison test revealed stronger overall network connectivity in middle schoolers compared to elementary schoolers but no differences between male and female students.ConclusionThe network approach elucidated the complex relationship of mutually influencing items within and between pediatric HRQOL and school social capital. Addressing central items may promote children's perceived health and school social capital.

Hydrogen sulfide (H2S) is a major physiologic gastrotransmitter. Its role in the regulation of the lower esophageal sphincter (LES) function remains unknown. The present study addresses this question. Methods: Isometric contraction was monitored in circular smooth muscle strips of porcine LES. Changes in cytosolic Ca2+ concentration ([Ca2+]i) and force were simultaneously monitored in fura-2-loaded strips with front-surface fluorometry. The contribution of endogenous H2S to LES contractility was investigated by examining the effects of inhibitors of H2S-generating enzymes, including cystathionine-β-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase, on the LES function. Results: Porcine LES strips myogenically maintained a tetrodotoxin-resistant basal tone. Application of AOA (cystathionine-β-synthase inhibitor) or L-aspartic acid (L-Asp; 3-mercaptopyruvate sulfurtransferase inhibitor) but not DL-PAG (cystathionine-γ-lyase inhibitor), decreased this basal tone. The relaxant effects of AOA and L-Asp were additive. Maximum relaxation was obtained by combination of 1 mM AOA and 3 mM L-Asp. Immunohistochemical analyses revealed that cystathionine-β-synthase and 3-mercaptopyruvate sulfurtransferase, but not cystathionine-γ-lyase, were expressed in porcine LES. AOA+L-Asp–induced relaxation was accompanied by a decrease in [Ca2+]i and inversely correlated with the extracellular Na+ concentration ([Na+]o) (25-137.4 mM), indicating involvement of an Na+/Ca2+ exchanger. The reduction in the basal [Ca2+]i level by AOA was significantly augmented in the antral smooth muscle sheets of Na+/Ca2+ exchanger transgenic mice compared with wild-type mice. Conclusions: Endogenous H2S regulates the LES myogenic tone by maintaining the basal [Ca2+]i via Na+/Ca2+ exchanger. H2S-generating enzymes may be a potential therapeutic target for esophageal motility disorders, such as achalasia.

Recent studies have established important roles of de novo mutations (DNMs) in autism spectrum disorders (ASDs). Here, we analyze DNMs in 262 ASD probands of Japanese origin and confirm the “de novo paradigm” of ASDs across ethnicities. Based on this consistency, we combine the lists of damaging DNMs in our and published ASD cohorts (total number of trios, 4,244) and perform integrative bioinformatics analyses. Besides replicating the findings of previous studies, our analyses highlight ATP-binding genes and fetal cerebellar/striatal circuits. Analysis of individual genes identified 61 genes enriched for damaging DNMs, including ten genes for which our dataset now contributes to statistical significance. Screening of compounds altering the expression of genes hit by damaging DNMs reveals a global downregulating effect of valproic acid, a known risk factor for ASDs, whereas cardiac glycosides upregulate these genes. Collectively, our integrative approach provides deeper biological and potential medical insights into ASDs.

Lrfn2/SALM1 is a synaptic adhesion molecule, and is known to interact with PSD-95. Here the authors show that Lrfn2 regulates excitatory synapse maturation and maintenance, and that Lrfn2 knockout mice exhibit autism-like behaviours as well as enhanced learning and memory.

It has been reported that neuroinflammation occurs in the central nervous system (CNS) in patients with neuropathic pain, Alzheimer's disease and autism spectrum disorder. The 18-kDa translocator protein TSPO is used as an imaging target in positron emission tomography to detect neuroinflammation, and its expression is correlated with microglial activation. However, the mechanism underlying the transcriptional regulation of Tspo induced by inflammation is not clear. Here, we revealed that lipopolysaccharide (LPS) -induced Tspo expression was activated by the AP-1 complex in a mouse microglial cell line, BV-2. Knockdown of c-Fos and c-Jun, the components of AP-1, reduced LPS-induced Tspo expression. Furthermore, the enrichment of Sp1 in the proximal promoter region of Tspo was increased in the presence of LPS. In addition, the binding of histone deacetylase 1 (HDAC1) to the enhancer region, which contains the AP-1 site, was decreased by LPS treatment, but there were no significant differences in HDAC1 binding to the proximal promoter region with or without LPS. These results indicated that HDAC1 is involved not in the proximal promoter region but in the enhancer region. Our study revealed that inflammatory signals induce the recruitment of AP-1 to the enhancer region and Sp1 to the proximal promoter region of the Tspo gene and that Sp1 may regulate the basal expression of Tspo.

In this study, we assessed the factor structure and construct validity of the parent-reported Inventory of Callous-Unemotional Traits (ICU) among school-aged children and adolescents, aged 6 to 15 years, in a community setting in Japan (n = 10,936). We investigated 15 models that have been reported in previous studies and used confirmatory factor analyses to determine a model that might actually be the best-fit among these. We then examined the correlations between the score of ICU and the Strengths and Difficulties Questionnaire (SDQ) in the best fit model and the three-factor bifactor (3FBF) model with the original ICU through cross-sectional and longitudinal analysis to determine the concurrent and predictive validity of the ICU. The results showed that the best-fit model was the two-factor bifactor (2FBF) model with a revised version of the ICU with 12 items, excluding all but one item of unemotional factors. The cross-sectional and longitudinal analysis showed that higher general callous-unemotional factor scores, callousness and uncaring specific factor scores were significantly associated with a higher level of conduct problems and a lower level of prosocial behaviors in the SDQ. These tendencies were shown both in the 2FBF model with the revised version of the ICU and the 3FBF model with the original ICU. We conclude that the 2FBF model was useful for school-aged community samples, as it predicts increases in conduct problems and decreases in prosocial behavior with fewer items than the 3FBF model.

Background/AimsThe ability of endoscopic submucosal dissection (ESD) to resect large early gastric cancers (EGCs) results in the need to treat large artificial gastric ulcers. This study assessed whether the combination therapy of rebamipide plus a proton pump inhibitor (PPI) offered benefits over PPI monotherapy.Methods : In this prospective, randomized, multicenter, open-label, and comparative study, patients who had undergone ESD for EGC or gastric adenoma were randomized into groups receiving either rabeprazole monotherapy (10 mg/day, n=64) or a combination of rabeprazole plus rebamipide (300 mg/day, n=66). The Scar stage (S stage) ratio after treatment was compared, and factors independently associated with ulcer healing were identified by using multivariate analyses.Results : The S stage rates at 4 and 8 weeks were similar in the two groups, even in the subgroups of patients with large amounts of tissue resected and regardless of CYP2C19 genotype. Independent factors for ulcer healing were circumferential location of the tumor and resected tissue size; the type of treatment did not affect ulcer healing.Conclusion : sCombination therapy with rebamipide and PPI had limited benefits compared with PPI monotherapy in the treatment of post-ESD gastric ulcer (UMIN Clinical Trials Registry, UMIN000007435).

[This corrects the article DOI: 10.1371/journal.pone.0199590.].

The Autism Spectrum Screening Questionnaire (ASSQ) is equipped with good properties for screening the broader phenotype of autistic traits, but it is standardized for a limited age range-from 7 to 16 years. To contribute to the early detection of Autism Spectrum Disorder (ASD), particularly in high functioning children with ASD, likely to cause maladjustments during school age, the present study examined psychometric properties to apply the ASSQ to a younger age. We tested parents' ASSQ ratings for preschool children in clinical (N = 154, average age 60.77 months, range 55-72 months) and community settings (N = 1390, average age 60.53 months, range 57-68 months) in Japan. The results showed, just as in school-aged children, the ASSQ had reliability and validity as a screening instrument for preschool children in community settings. A cut-off of 7 with sensitivity of 0.93 and specificity of 0.84 is recommended for community screening. Still, based on the current study with a clinical group, an optimal cut-off score with high sensitivity and high specificity for parents' ASSQ ratings could not be established. The clinicians should be reminded that the ASSQ is a screening instrument, not a diagnosing instrument. Also, this result suggest multi-faceted evaluation is necessary in clinical settings, for example, the addition of teachers' ratings.

Here we discuss the development of a novel cell imaging system for the evaluation of smooth muscle cell (SMC) contraction. SMCs were isolated from the circular and longitudinal muscular layers of mouse small intestine by enzymatic digestion. SMCs were stimulated by test agents, thereafter fixed in acrolein. Actin in fixed SMCs was stained with phalloidin and cell length was determined by measuring diameter at the large end of phalloidin-stained strings within the cells. The contractile response was taken as the decrease in the average length of a population of stimulated-SMCs. Various mediators and chemically identified compounds of daikenchuto (DKT), pharmaceutical-grade traditional Japanese prokinetics, were examined. Verification of the integrity of SMC morphology by phalloidin and DAPI staining and semi-automatic measurement of cell length using an imaging analyzer was a reliable method by which to quantify the contractile response. Serotonin, substance P, prostaglandin E2 and histamine induced SMC contraction in concentration-dependent manner. Two components of DKT, hydroxy-α-sanshool and hydroxy-β-sanshool, induced contraction of SMCs. We established a novel cell imaging technique to evaluate SMC contractility. This method may facilitate investigation into SMC activity and its role in gastrointestinal motility, and may assist in the discovery of new prokinetic agents.

A preoperative diagnosis of solid pseudopapillary neoplasms (SPNs) in young male patients is difficult to achieve using radiological images. We herein present three cases of young male patients with relatively small SPNs. Endoscopic ultrasound (EUS) showed well-encapsulated, smooth-surfaced, heterogeneous solid lesions in all patients, and all preoperative diagnoses were achieved by EUS-guided fine needle aspiration (EUS-FNA). The final pathological diagnosis after surgery was an SPN with a Ki-67 labeling index of

Background and study aims: The Clutch Cutter (CC) was developed to reduce the risk of complications related to endoscopic submucosal dissection (ESD) using knives. The CC is able to grasp and coagulate and/or incise the targeted tissue using electrosurgical current, like a biopsy technique. The aim of this study was to evaluate the efficacy and safety of ESD using the CC (ESD-CC) for early gastric cancer (EGC). Patients and methods: From June 2007 to March 2014, 325 consecutive patients with a diagnosis of EGC were enrolled in this prospective study. They had all satisfied the Japanese gastric cancer treatment guidelines for ESD indication, namely confirmation by preliminary endoscopy, endoscopic ultrasound, and endoscopic biopsies. The CC was used for all steps of ESD (marking, circumferential marginal incision, submucosal dissection, and hemostatic treatment). The therapeutic efficacy and safety were assessed. Results: The en-bloc resection rate was 99.7 % (324/325) and the R0 resection rate was 95.3 % (310/325). The mean operating time was 97.2 minutes. Perforation during ESD-CC occurred in one case (0.3 %), which was managed with conservative medical treatment after endoscopic closure of the perforation. Post-ESD-CC bleeding occurred in 11 cases (3.4 %), which were successfully treated by endoscopic hemostatic treatment. The R0 resection rate was significantly low in tumors > 20 mm (88.9 %), and in the exclusion indication group (73.7 %). Significant differences were seen in the mean operating time, depending upon tumor size, histologic type, location, and indication criteria. Conclusions: ESD-CC is a technically efficient, safe, and easy method for resecting EGC.

Participatory sensing is the process in which individuals or communities collect and analyze systematic data using mobile phones and cloud services. To efficiently develop participatory sensing services, some server-side technologies have been proposed. Although they provide a good platform for participatory sensing, they are not optimized for spatial data management and processing. For the purpose of spatial data collection and management, many web GIS approaches have been studied. However, they still have not focused on the optimal framework for participatory sensing services. This paper presents a web GIS framework for participatory sensing service (FPSS). The proposed FPSS enables an integrated deployment of spatial data capture, storage, and data management functions. In various types of participatory sensing experiments, users can collect and manage spatial data in a unified manner. This feature is realized by the optimized system architecture and use case based on the general requirements for participatory sensing. We developed an open source GIS-based implementation of the proposed framework, which can overcome financial difficulties that are one of the major problems of deploying sensing experiments. We confirmed with the prototype that participatory sensing experiments can be performed efficiently with the proposed FPSS.

Background and aimThe etiology of post-inflammatory gastrointestinal (GI) motility dysfunction, after resolution of acute symptoms of inflammatory bowel diseases (IBD) and intestinal infection, is largely unknown, however, a possible involvement of T cells is suggested.MethodsUsing the mouse model of T cell activation-induced enteritis, we investigated whether enhancement of smooth muscle cell (SMC) contraction by interleukin (IL)-17A is involved in postinflammatory GI hypermotility.ResultsActivation of CD3 induces temporal enteritis with GI hypomotility in the midst of, and hypermotility after resolution of, intestinal inflammation. Prolonged upregulation of IL-17A was prominent and IL-17A injection directly enhanced GI transit and contractility of intestinal strips. Postinflammatory hypermotility was not observed in IL-17A-deficient mice. Incubation of a muscle strip and SMCs with IL-17A in vitro resulted in enhanced contractility with increased phosphorylation of Ser19 in myosin light chain 2 (p-MLC), a surrogate marker as well as a critical mechanistic factor of SMC contractility. Using primary cultured murine and human intestinal SMCs, IκBζ- and p38 mitogen-activated protein kinase (p38MAPK)-mediated downregulation of the regulator of G protein signaling 4 (RGS4), which suppresses muscarinic signaling of contraction by promoting inactivation/desensitization of Gαq/11 protein, has been suggested to be involved in IL-17A-induced hypercontractility. The opposite effect of L-1β was mediated by IκBζ and c-jun N-terminal kinase (JNK) activation.ConclusionsWe propose and discuss the possible involvement of IL-17A and its downstream signaling cascade in SMCs in diarrheal hypermotility in various GI disorders.

The present study aimed at investigating whether neuromotor development, from birth to 14 months of age, shows seasonal, cyclic patterns in association with months of birth. Study participants were 742 infants enrolled in the Hamamatsu Birth Cohort (HBC) Study and followed-up from birth to the 14th month of age. Gross motor skills were assessed at the ages of 6, 10, and 14 months, using Mullen Scales of Early Learning. The score at each assessment was regressed onto a trigonometric function of months of birth, with an adjustment for potential confounders. Gross motor scores at the 6th and 10th months showed significant 1-year-cycle variations, peaking among March- and April-born infants, and among February-born infants, respectively. Changes in gross motor scores between the 10th and 14th months also showed a cyclic variation, peaking among July- and August-born infants. Due to this complementary effect, gross motor scores at the 14th month did not show seasonality. Neuromotor development showed cyclic seasonality during the first year of life. The effects brought about by month of birth disappeared around 1 year of age, and warmer months seemed to accelerate the neuromotor development.

It has recently been hypothesized that hyperglutamatergia in the brain is involved in the pathophysiology of autism. However, there is no conclusive evidence of the validity of this hypothesis. As peripheral glutamate/glutamine levels have been reported to be correlated with those of the central nervous system, the authors examined whether the levels of 25 amino acids, including glutamate and glutamine, in the platelet-poor plasma of drug-naïve, male children with high-functioning autism (HFA) would be altered compared with those of normal controls.Plasma levels of 25 amino acids in male children (N = 23) with HFA and normally developed healthy male controls (N = 22) were determined using high-performance liquid chromatography. Multiple testing was allowed for in the analyses. Compared with the normal control group, the HFA group had higher levels of plasma glutamate and lower levels of plasma glutamine. No significant group difference was found in the remaining 23 amino acids. The effect size (Cohen's d) for glutamate and glutamine was large: 1.13 and 1.36, respectively. Using discriminant analysis with logistic regression, the two values of plasma glutamate and glutamine were shown to well-differentiate the HFA group from the control group; the rate of correct classification was 91%.The present study suggests that plasma glutamate and glutamine levels can serve as a diagnostic tool for the early detection of autism, especially normal IQ autism. These findings indicate that glutamatergic abnormalities in the brain may be associated with the pathobiology of autism.

Accumulating evidence suggests that dysregulation of the immune system is involved in the pathophysiology of autism spectrum disorders (ASD). The aim of the study was to explore immunological markers in peripheral plasma samples from non-medicated subjects with high-functioning ASD.A multiplex assay for cytokines and chemokines was applied to plasma samples from male subjects with high-functioning ASD (n = 28) and matched controls (n = 28). Among a total of 48 analytes examined, the plasma concentrations of IL-1β, IL-1RA, IL-5, IL-8, IL-12(p70), IL-13, IL-17 and GRO-α were significantly higher in subjects with ASD compared with the corresponding values of matched controls after correction for multiple comparisons.The results suggest that abnormal immune responses as assessed by multiplex analysis of cytokines may serve as one of the biological trait markers for ASD.

Multiple lines of evidence suggest a serotoninergic dysfunction in autism. The role of LMX1B in the development and maintenance of serotoninergic neurons is well known. In order to examine the role, if any, of LMX1B with autism pathophysiology, a trio-based SNP association study using 252 family samples from the AGRE was performed. Using pair-wise tagging method, 24 SNPs were selected from the HapMap data, based on their location and minor allele frequency. Two SNPs (rs10732392 and rs12336217) showed moderate association with autism with p values 0.018 and 0.022 respectively in transmission disequilibrium test. The haplotype AGCGTG also showed significant association (p = 0.008). Further, LMX1B mRNA expressions were studied in the postmortem brain tissues of autism subjects and healthy controls samples. LMX1B transcripts was found to be significantly lower in the anterior cingulate gyrus region of autism patients compared with controls (p = 0.049). Our study suggests a possible role of LMX1B in the pathophysiology of autism. Based on previous reports, it is likely to be mediated through a seretoninergic mechanism. This is the first report on the association of LMX1B with autism, though it should be viewed with some caution considering the modest associations we report.

BackgroundEpidemiological studies suggest that radiation exposure may be a potential risk factor for schizophrenia in adult humans. Here, we investigated whether adult irradiation in rats caused behavioral abnormalities relevant to schizophrenia.Methodology/principal findingsA total dose of 15-Gy irradiation in six fractionations during 3 weeks was exposed to the forebrain including the subventricular zone (SVZ) and subgranular zone (SGZ) with male rats in the prone position. Behavioral, immunohistochemical, and neurochemical studies were performed three months after fractionated ionizing irradiation. Three months after fractionated ionizing irradiation, the total numbers of BrdU-positive cells in both the SVZ and SGZ zones of irradiated rats were significantly lower than those of control (sham-irradiated) rats. Hyperactivity after administration of the dopaminergic agonist methamphetamine, but not the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine, was significantly enhanced in the irradiated rats although spontaneous locomotion in the irradiated rats was significantly lower than that of controls. Behavioral abnormalities including auditory sensory gating deficits, social interaction deficits, and working memory deficits were observed in the irradiated rats.Conclusion/significanceThe present study suggests that irradiation in adulthood caused behavioral abnormalities relevant to schizophrenia, and that reduction of adult neurogenesis by irradiation may be associated with schizophrenia-like behaviors in rats.

BACKGROUND: Obstetric complications have been regarded as a risk factor for schizophrenia later in life. One of the mechanisms underlying the association is postulated to be a hypoxic process in the brain in the offspring around the time of birth. Hippocampus is one of the brain regions implicated in the late-onset dopaminergic dysfunction associated with hypoxic obstetric complications. METHODOLOGY/PRINCIPAL FINDINGS: We used an animal model of perinatal asphyxia, in which rat pups were exposed to 15 min of intrauterine anoxia during Cesarean section birth. At 6 and 12 weeks after birth, the behavior of the pups was assessed using a methamphetamine-induced locomotion test. In addition, the histopathology of the hippocampus was examined by means of stereology. At 6 weeks, there was no change in the methamphetamine-induced locomotion. However, at 12 weeks of age, we found an elevation in methamphetamine-induced locomotor activity, which was associated with an increase of dopamine release in the nucleus accumbens. At the same age, we also found a reduction of the dentate granule cells of the hippocampus. CONCLUSIONS/SIGNIFICANCE: These results suggest that the dopaminergic dysregulation after perinatal asphyxia is associated with a reduction in hippocampal dentate granule cells, and this may partly contribute to the pathogenesis of schizophrenia.

The synthesis of (−)-complanine, an inflammatory substance of Eurythoe complanata, was accomplished by a “chiral synthon” approach. The absolute configuration of this molecule was determined to be R.

Treatment-related neuroendocrine prostate cancer (tNEPC) occurs after androgen deprivation therapy and has a poor prognosis; however, there are few effective treatments for tNEPC. Therefore, tNEPC management is often challenging. This is a case of a 65-year-old Asian male patient with prostate adenocarcinoma who had metastases at initial presentation. After prostate biopsy revealed neuroendocrine prostate cancer (NEPC), he was treated with platinum-based systemic chemotherapy followed by pembrolizumab treatment. The primary tumor regions temporarily regressed, but progression of the primary tumor resulted in urinary retention and rectal obstruction; therefore, a transverse colostomy was performed, and a urethral catheter was inserted. Following somatostatin receptor scintigraphy (SRS), it was determined that the primary tumor expressed somatostatin receptors. Based on these results, treatment with 177Lu-DODATATE peptide receptor radionuclide therapy was prescribed. Subsequently, the primary tumor regressed remarkably, and the urethral catheter was removed. 177Lu-DOTATATE peptide receptor radionuclide therapy may be an effective option for tNEPC, which has few effective treatment options. [ABSTRACT FROM AUTHOR]