Utility of combining multiple parameters of 123I-IMP SPECT and voxel-based morphometry MRI using a multiparametric scoring system for differentiating dementia with Lewy bodies from Alzheimer's disease.

BACKGROUND: Brain magnetic resonance imaging voxel-based morphometry (VBM) and perfusion single-photon emission computed tomography (SPECT) are useful for differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). PURPOSE: To determine whether combining multiple parameters of VBM and SPECT using a multiparametric scoring system (MSS) improves diagnostic accuracy in differentiating DLB from AD. MATERIAL AND METHODS: In total, 23 patients with DLB and 57 patients with AD underwent imaging using a voxel-based specific regional analysis system for AD (VSRAD), an easy Z-score imaging system, and a Z-Graph using three-dimensional stereotactic surface projection. The cutoff values were determined using the receiver operating characteristic curve to differentiate DLB from AD for all parameters. Patients were scored 1 (DLB) or 0 (AD) for each statistically significant parameter, according to a threshold. The total score was determined for each case to obtain a cutoff value for the MSS. RESULTS: The mean Z-scores in the medial temporal lobes using the VSRAD were significantly lower in patients with DLB than in those with AD. Each Z-score of the summed Z-scores in all four segmented regions of the occipital lobes using the Z-Graph was significantly higher in patients with DLB than in those with AD. Among the five parameters, the highest accuracy was 80% for the Z-score of the summed Z-scores in the left medial occipital lobe. For the MSS, a cutoff value of four improved the diagnostic accuracy to 82%. CONCLUSION: MSS was more accurate than any single parameter of VBM or SPECT in differentiating DLB from AD.

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.

Molecular diagnosis of 405 individuals with autism spectrum disorder.

Autism spectrum disorder (ASD) is caused by combined genetic and environmental factors. Genetic heritability in ASD is estimated as 60-90%, and genetic investigations have revealed many monogenic factors. We analyzed 405 patients with ASD using family-based exome sequencing to detect disease-causing single-nucleotide variants (SNVs), small insertions and deletions (indels), and copy number variations (CNVs) for molecular diagnoses. All candidate variants were validated by Sanger sequencing or quantitative polymerase chain reaction and were evaluated using the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines for molecular diagnosis. We identified 55 disease-causing SNVs/indels in 53 affected individuals and 13 disease-causing CNVs in 13 affected individuals, achieving a molecular diagnosis in 66 of 405 affected individuals (16.3%). Among the 55 disease-causing SNVs/indels, 51 occurred de novo, 2 were compound heterozygous (in one patient), and 2 were X-linked hemizygous variants inherited from unaffected mothers. The molecular diagnosis rate in females was significantly higher than that in males. We analyzed affected sibling cases of 24 quads and 2 quintets, but only one pair of siblings shared an identical pathogenic variant. Notably, there was a higher molecular diagnostic rate in simplex cases than in multiplex families. Our simulation indicated that the diagnostic yield is increasing by 0.63% (range 0-2.5%) per year. Based on our simple simulation, diagnostic yield is improving over time. Thus, periodical reevaluation of ES data should be strongly encouraged in undiagnosed ASD patients.

Trajectories of emotional and behavioral problems in school-age children with coordination difficulties and their relationships to ASD/ADHD traits.

BACKGROUND: Although research has demonstrated associations between motor coordination difficulties and psychological problems in school-age children, including emotional and behavioral problems, longitudinal changes in these problems in children with motor coordination difficulties are not fully understood. AIMS: The current study aimed to identify patterns in the trajectory of emotional and behavioral problems in school-age children with motor coordination difficulties, and to elucidate the effect of co-existing neurodevelopmental traits on the occurrence and course of these problems. METHODS AND PROCEDURES: Using the Developmental Coordination Disorder Questionnaire, 773 children were defined as cases with motor coordination difficulties and followed for 4 years, from 6 to 10 years of age. Emotional and behavioral problems were assessed using the Strengths and Difficulties Questionnaire completed by children's parents or guardians. OUTCOMES AND RESULTS: We identified four trajectory patterns of emotional and behavioral problems. Children with higher autism spectrum disorder and attention deficit hyperactivity disorder traits were more likely to be assigned to poor prognostic trajectory patterns. CONCLUSIONS AND IMPLICATIONS: Our findings emphasize the importance of assessing emotional and behavioral problems and co-existing neurodevelopmental traits in children with motor coordination difficulties in early elementary school.

School Social Capital Mediates Associations Between ASD Traits and Depression Among Adolescents in General Population.

Though autism spectrum disorder (ASD) traits are associated with depression, it is unclear if school social capital mediates their association. We examined whether school social capital mediates the association between ASD traits and depression, and moderation effect of sex on the mediation effect among adolescents in a general population sample (1750 males, 1779 females; equivalent 12-15 years old). The results of this study indicate that ASD traits are associated with depression among adolescents, and that this association is partly mediated by school social capital. Furthermore, the results of the moderated mediation analysis suggest that lower level of school social capital can lead to more increase level of depression for females than for males.

High Signal Intensity of the Cochlear Modiolus on Unenhanced T1-Weighted Images in Classical Infratentorial Superficial Siderosis.

Background: Superficial siderosis (SS) results from chronic bleeding in the subarachnoid space. SS can be classified as infratentorial SS (i-SS) and supratentorial SS (s-SS). The cochlear modiolus (CM) normally shows low signal intensity (SI) on Tl-weighted images (T1WI). We noticed persistently high SI of the CM on unenhanced thin-sliced T1WI in patients with i-SS. The purpose of this study was to evaluate the correlation between SS and high SI of the CM on unenhanced T1WI. Methods: This retrospective study analyzed three cases with i-SS, eight cases with s-SS, and 23 normal controls (NC) evaluated on unenhanced thin-sliced T1WI with a three-dimensional spoiled gradient-recalled echo sequence. CM-T1SI scores of 0, 1, and 2 indicated low, iso, and high SI, respectively. In cases with scores of 2 evaluated several times, all scores were reviewed for each case. The CM-T1SI ratio was defined as the contrast ratio between the CM and the cerebellum. Differences between the three groups were statistically analyzed based on the CM-T1SI score and ratio. Receiver operative curve (ROC) analysis was used to determine the cut-off values for differentiating the i-SS group from the NC group based on the CM-T1SI ratio. Results: Two patients with i-SS had a score of 2 on all evaluations. The CM-T1SI score and ratio differed significantly between the i-SS and NC groups. The accuracy of the CM-T1SI ratio for discriminating i-SS from NC was 98.9% at a cutoff value of 0.628. Conclusion: High SI of the CM on unenhanced TIWI can be an additional characteristic finding of i-SS.

The Role of the Maternal and Child Health Handbook in Developmental Surveillance: The Exploration of Milestone Attainment Trajectories.

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.

Advanced magnetic resonance imaging findings of cerebellar hemangioblastomas: A report of three cases and a literature review.

On conventional magnetic resonance imaging (MRI), hemangioblastomas typically appear as mural nodules with an adjacent surrounding cyst or a solid mass in the cerebellum. However, hemangioblastomas sometimes cannot be reliably distinguished using this imaging technique from other tumors, especially pilocytic astrocytomas and metastatic tumors, because of their similar imaging findings and locations. Herein, we report three cases of cerebellar hemangioblastomas and review their findings on conventional and advanced MRI, including diffusion-weighted imaging (DWI), dynamic susceptibility-weighted contrast-enhanced perfusion-weighted imaging (DSC-PWI), and magnetic resonance spectroscopy (MRS). Solid contrast-enhanced lesions of hemangioblastomas showed increased apparent diffusion coefficient values on DWI, increased relative cerebral blood volume ratio on DSC-PWI, and high lipid/lactate peak on MRS. Therefore, advanced MRI techniques can be helpful in understanding the pathological and metabolic changes of hemangioblastomas and may be useful for their characterization.

Toward mapping pragmatic impairment of autism spectrum disorder individuals through the development of a corpus of spoken Japanese.

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.

Two Patients with Schizophrenia Treated with Clozapine Developed Neutropenia After Receiving a COVID-19 Vaccine.

BACKGROUND: We observed two cases of patients with schizophrenia who were treated with clozapine (250mg/day and 275mg/day, respectively) and showed neutropenia after receiving a COVID-19 vaccine (BNT162b2). CASE PRESENTATION: Case 1 is a twenty-two year old woman with a diagnosis of schizophrenia. She enrolled in Clozaril® Patient Monitoring Service in 2017 and had been taking clozapine for 4 years. She received two doses of a COVID-19 vaccine and developed neutropenia (1850/mm3 (37.9% of white blood cell 4880/mm3)) 6 days after the second vaccination, but her neutropenia self-resolved naturally. Case 2 is a twenty year old woman with a diagnosis of schizophrenia. She enrolled in Clozaril® Patient Monitoring Service in 2020 and had been taking clozapine for 10 months. She received two doses of a COVID-19 vaccine and white blood cell and neutrocyte counts were below (3730/mm3 and 1440/mm3 (38.6%), respectively) the lower limits 3 days after the second vaccination. She had to discontinue clozapine according to the withdrawal definition (her neutrocyte count was <1500/mm3), and her neutropenia self-resolved naturally. CONCLUSION: Physicians need to have a strict follow-up protocol in place for patients after vaccination for COVID-19.

The association of social capital with depression and quality of life in school-aged children.

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.

Longitudinal association between smartphone ownership and depression among schoolchildren under COVID-19 pandemic.

Under the COVID-19 pandemic, concerns regarding prolonged screen time and mental health effects in children have increased. We examined the association of depression with smartphone ownership in school children at four time points: September 2019, July 2020, December 2020, and March 2021. The analysis revealed an interaction between group and time, indicating that depressive symptoms among smartphone owners were significantly more severe than in the other group. These results were clearer for fourth-year students, pointing that smartphone possession at younger ages may be a risk factor for mental health in the new lifestyle caused by the COVID-19 pandemic.

Automatic one-click planning for hippocampal-avoidance whole-brain irradiation in RayStation.

This study aimed to verify the accuracy of auto-contouring and auto-dose optimization for hippocampal-avoidance whole-brain radiation therapy (HA-WBRT). Head computed tomography (CT) images of 15 patients were selected. The regions of interest, containing the brain, hippocampus, eyes, and lacrimal glands, were contoured manually and automatically on CT images. They were compared and evaluated for concordance rates using the Simpson coefficient. To verify the performance of dose optimization, auto-dose planning was compared with manual planning for 15 cases. All optimization plans were performed using the volumetric modulated arc therapy technique. The automatically contoured brain showed a very high concordance rate with the manually contoured brain; the Simpson coefficient was 0.990 ± 0.01. Contrastingly, the concordance rate of the hippocampal contour was low at 0.642 ± 0.15 (right) and 0.500 ± 0.16 (left); however, the rate improved to 0.871 ± 0.09 (right) and 0.852 ± 0.11 (left) with an additional 3-mm margin. For 2% of each planning target volume with the prescribed dose (D2%) and Dmean, there was no significant difference between the automatic and manual plans (35.50 Gy vs 35.23 Gy; p = 0.233 and 33.09 Gy vs 32.84 Gy; p = 0.073, respectively). The D98% was significantly better for the manual plan than for the automatic plan (25.49 Gy vs 26.11 Gy; p < 0.01). Dmax and D100% for the hippocampus did not show any significant difference between the automatic and manual plans (15.65, 16.09 Gy (right, left) vs 15.51, 15.80 Gy; p = 0.804, 0.233 and 8.08, 8.03 Gy vs 8.13, 8.01 Gy; p = 0.495, 1 respectively). The accuracy of auto-contouring for HA-WBRT can be guaranteed by providing an appropriate margin, and the precision of the auto-dose optimization was comparable to that of the manual plan.

JNETS clinical practice guidelines for gastroenteropancreatic neuroendocrine neoplasms: diagnosis, treatment, and follow-up: a synopsis.

Neuroendocrine neoplasms (NENs) are rare neoplasms that occur in various organs and present with diverse clinical manifestations. Pathological classification is important in the diagnosis of NENs. Treatment strategies must be selected according to the status of differentiation and malignancy by accurately determining whether the neoplasm is functioning or nonfunctioning, degree of disease progression, and presence of metastasis. The newly revised Clinical Practice Guidelines for Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs) comprises 5 chapters-diagnosis, pathology, surgical treatment, medical and multidisciplinary treatment, and multiple endocrine neoplasia type 1 (MEN1)/von Hippel-Lindau (VHL) disease-and includes 51 clinical questions and 19 columns. These guidelines aim to provide direction and practical clinical content for the management of GEP-NEN preferentially based on clinically useful reports. These revised guidelines also refer to the new concept of "neuroendocrine tumor" (NET) grade 3, which is based on the 2017 and 2019 WHO criteria; this includes health insurance coverage of somatostatin receptor scintigraphy for NEN, everolimus for lung and gastrointestinal NET, and lanreotide for GEP-NET. The guidelines also newly refer to the diagnosis, treatment, and surveillance of NEN associated with VHL disease and MEN1. The accuracy of these guidelines has been improved by examining and adopting new evidence obtained after the first edition was published.

Mucosal IL23A expression predicts the response to Ustekinumab in inflammatory bowel disease.

BACKGROUND: Biologics against tumor necrosis factor-α (TNF) and the p40 subunit of interleukin (IL)-12 and IL-23 are increasingly used in inflammatory bowel disease (IBD) treatment. However, information on response prediction to these agents is limited. Thus, we aimed to identify factors for IBD treatment response prediction. METHODS: We conducted a retrospective study in 33 IBD subjects for anti-TNF and a prospective study of 23 IBD and 11 non-IBD subjects for ustekinumab (UST). Mucosal biopsy specimens were obtained before treatment with biologics. The expression of 18 immune-related genes encoding representative cytokines and transcription factors was analyzed by quantitative polymerase chain reaction. RESULTS: There was no difference between the treatment-resistant and -sensitive groups with regard to clinical characteristics. A higher expression of oncostatin M (OSM) and its receptor OSMR in the intestinal mucosa was most strongly associated with anti-TNF resistance, whereas lower IL23A expression was most strongly associated with UST resistance. In addition to the absolute expression levels of genes, concordant or discordant expression patterns of particular gene sets were associated with treatment sensitivity and resistance. CONCLUSIONS: The association of anti-TNF resistance and mucosal OSM and OSMR expression was consistent with the results of a previous study in a European cohort. Our observation that IBD subjects with higher mucosal IL23A expression were more likely to achieve remission by UST has not been previously reported. The response to biologics may thus be predicted in IBD patients through the analysis of mucosal gene expression levels and patterns.

Utility of 3T single-voxel proton MR spectroscopy for differentiating intracranial meningiomas from intracranial enhanced mass lesions.

BACKGROUND: Proton magnetic resonance spectroscopy (MRS) provides structural and metabolic information that is useful for the diagnosis of meningiomas with atypical radiological appearance. However, the metabolite that should be prioritized for the diagnosis of meningiomas has not been established. PURPOSE: To evaluate the differences between the metabolic peaks of meningiomas and other intracranial enhanced mass lesions (non-meningiomas) using MR spectroscopy in short echo time (TE) spectra and the most useful metabolic peak for discriminating between the groups. MATERIAL AND METHODS: The study involved 9 meningiomas, 22 non-meningiomas, intracranial enhancing tumors and abscesses, and 15 normal controls. The ranking of the peak at 3.8 ppm, peak at 3.8 ppm/Creatine (Cr), ß-γ Glutamine-Glutamate (bgGlx)/Cr, N-acetyl compounds (NACs)/Cr, choline (Cho)/Cr, lipid and/or lactate (Lip-Lac) at 1.3 ppm/Cr, and the presence of alanine (Ala) were derived. The metabolic peaks were compared using the Mann-Whitney U test. ROC analysis was used to determine the cut-off values for differentiating meningiomas from non-meningiomas using statistically significant metabolic peaks. RESULTS: The ranking of the peak at 3.8 ppm among all the peaks, peak at 3.8 ppm/Cr, bgGlx/Cr, Lip-Lac/Cr, and the presence of Ala discriminated meningiomas from non-meningiomas with moderate to high accuracy. The highest accuracy was 96.9% at a threshold value of 3 for the rank of the peak at 3.8 ppm. CONCLUSION: A distinct elevated peak at 3.8 ppm, ranked among the top three highest peaks, allowed the detection of meningiomas.

A loss-of-function variant in SUV39H2 identified in autism-spectrum disorder causes altered H3K9 trimethylation and dysregulation of protocadherin ß-cluster genes in the developing brain.

Recent evidence has documented the potential roles of histone-modifying enzymes in autism-spectrum disorder (ASD). Aberrant histone H3 lysine 9 (H3K9) dimethylation resulting from genetic variants in histone methyltransferases is known for neurodevelopmental and behavioral anomalies. However, a systematic examination of H3K9 methylation dynamics in ASD is lacking. Here we resequenced nine genes for histone methyltransferases and demethylases involved in H3K9 methylation in individuals with ASD and healthy controls using targeted next-generation sequencing. We identified a novel rare variant (A211S) in the SUV39H2, which was predicted to be deleterious. The variant showed strongly reduced histone methyltransferase activity in vitro. In silico analysis showed that the variant destabilizes the hydrophobic core and allosterically affects the enzyme activity. The Suv39h2-KO mice displayed hyperactivity and reduced behavioral flexibility in learning the tasks that required complex behavioral adaptation, which is relevant for ASD. The Suv39h2 deficit evoked an elevated expression of a subset of protocadherin ß (Pcdhb) cluster genes in the embryonic brain, which is attributable to the loss of H3K9 trimethylation (me3) at the gene promoters. Reduced H3K9me3 persisted in the cerebellum of Suv39h2-deficient mice to an adult stage. Congruently, reduced expression of SUV39H1 and SUV39H2 in the postmortem brain samples of ASD individuals was observed, underscoring the role of H3K9me3 deficiency in ASD etiology. The present study provides direct evidence for the role of SUV39H2 in ASD and suggests a molecular cascade of SUV39H2 dysfunction leading to H3K9me3 deficiency followed by an untimely, elevated expression of Pcdhb cluster genes during early neurodevelopment.

Implantable cardiac pacemaker failure by cumulative dose effects of flattening filter free beams.

Cumulative dose effects, which are one of the main causes of errors that occur when an implantable cardiac pacemaker (ICP) is irradiated with ionizing radiation, induce permanent failure in ICPs. Although flattening filter free (FFF) beams, which are often used in stereotactic radiotherapy, are known to have different characteristics from conventional (with flattening filter [WFF]) beams, the cumulative dose effects on ICPs with FFF beams have been under-investigated. This study investigates ICP failure induced by cumulative dose effects of FFF beams. When the ICP placed in the center of the irradiation field was irradiated with 10 MV-FFF at 24 Gy/min, the cumulative dose at which failure occurred was evaluated on the basis of the failure criteria associated with high cumulative dose as described in the American Association of Physicists in Medicine Task Group 203. The ICP failures such as a mild battery depletion at a cumulative dose of 10 Gy, pacing-output voltage change >25% at a cumulative dose of 122 Gy, and the loss of telemetry capability at cumulative dose 134 Gy were induced by cumulative dose effects. The cumulative doses by which the cumulative dose effects of FFF beams induced ICP failure were not very different from those reported in previous studies with WFF beams. Therefore, radiotherapy with FFF beams (and WFF beams) for patients with ICP requires appropriate management for minimizing the cumulative dose effects.

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.