Functional AGXT2 SNP rs180749 variant and depressive symptoms: Baseline data from the Aidai Cohort Study in Japan.

No study has shown the relationship between alanine-glyoxylate aminotransferase 2 (AGXT2) single nucleotide polymorphisms (SNPs) and depressive symptoms. The present case-control study examined this relationship in Japanese adults. Cases and control participants were selected from those who participated in the baseline survey of the Aidai Cohort Study, which is an ongoing cohort study. Cases comprised 280 participants with depressive symptoms based on a Center for Epidemiologic Studies Depression Scale (CES-D) score ≥ 16. Control participants comprised 2034 participants without depressive symptoms based on the CES-D who had not been diagnosed by a physician as having depression or who had not been currently taking medication for depression. Adjustment was made for age, sex, smoking status, alcohol consumption, leisure time physical activity, education, body mass index, hypertension, dyslipidemia, and diabetes mellitus. Compared with the GG genotype of rs180749, both the GA and AA genotypes were significantly positively associated with the risk of depressive symptoms assessed by the CES-D: the adjusted odds ratios for the GA and AA genotypes were 2.83 (95% confidence interval [CI] 1.23-8.24) and 3.10 (95% CI 1.37-8.92), respectively. The TGC haplotype of rs37370, rs180749, and rs16899974 was significantly inversely related to depressive symptoms (crude OR 0.67; 95% CI 0.49-0.90), whereas the TAC haplotype was significantly positively associated with depressive symptoms (crude OR 1.24; 95% CI 1.01-1.52). This is the first study to show significant associations between AGXT2 SNP rs180749, the TGC haplotype, and the TAC haplotype and depressive symptoms.

Radiotherapy for ductal carcinoma of the prostate: an analysis based on the Japanese radiation oncology study group survey.

BACKGROUND: The clinical characteristics of prostate ductal carcinoma is still unclear, and treatment strategy has not yet been established due to its rarity. Therefore, we conducted a multicenter survey of radiation therapy for prostate ductal carcinoma in Japan. METHOD: Data of patients with ductal carcinoma of the prostate treated with radiation therapy between 1996 and 2018 were extracted from the database of each facility. RESULTS: Fifty-two treatment records of 41 patients were collected from nine institutions. The treatment purpose and situations were varied curative intent to palliation. Twenty-eight patients received curative treatments. The median follow-up period of these patients was 68 months. Androgen deprivation therapy was combined with radiation therapy in 26 cases (93%). X-ray and particle irradiation was used. Radiation dose range was 63-78 Gy; 5-year overall survival, progression-free survival and biochemical relapse-free survival were 87.0, 79.3 and 79.3%, respectively. One patient experienced Grade 3 radiation proctitis and one experienced Grade 3 radiation cystitis. There were no Grade 4 or worse adverse events. CONCLUSION: Most patient received similar treatment with adenocarcinoma of prostate, and the clinical results were compatible. For more reliable evidence, further studies are required.

Online training of Covid-19 infection prevention and control for healthcare workers in psychiatric institutes.

BACKGROUND: This study aimed to develop a unique online infection prevention and control (IPC) training on Covid-19 for healthcare workers in psychiatric institutes in Japan and to examine its efficacy based on its impact on the knowledge, attitude, and confidence about IPC for Covid-19 among the healthcare workers. METHOD: This quasi-experimental study was conducted using online training on Covid-19 IPC for healthcare workers in various psychiatric institutes from April 2021 to March 2022. An online training video on Covid-19 IPC was developed. Voluntary healthcare workers in psychiatric institutes located in five prefectures in Japan were recruited to participate in this training. The participants then completed 30 min of online training and surveys about knowledge, attitude, and confidence were conducted pre, post, and three months after the training. The video training and surveys were contextually validated by the experts, but not by any previous study. RESULTS: A total of 224 participants were included, of which 108 (54.0%) were men. The mean (standard deviation (SD)) age and the mean occupational experience were 47.4 (9.5) and 18.0 (12.6) years, respectively. Among the participants, 190 (84.8%) completed the post-training, and 131 (58.5%) completed the three-month-later training surveys. The total score on the quizzes in the post-training (+ 31.1%, SD 15.7, p-value < 0.01) and three-month-later training (+ 14.9%, SD 16.8, p-value < 0.01) surveys had significantly increased from that in the pre-training survey. In contrast, the total score in the three-month-later training had significantly decreased from that in the post-training survey (-16.1%, SD 16.7, p-value < 0.01). CONCLUSION: Thirty minutes of online training about IPC for Covid-19 had improved knowledge, confidence, and attitude among psychiatric healthcare workers. Regular online training would help in preventing the transmission or formation of clusters of Covid-19 in psychiatric healthcare institutes.

Dramatically Improved Severe Pulmonary Arterial Hypertension Caused by Qing-Dai (Chinese Herbal Drug) for Ulcerative Colitis.

Pulmonary arterial hypertension (PAH) is a rare and fatal disease for which some causative drugs have been developed. Qing-Dai is a Chinese herbal drug that is sometimes used as a specific treatment for ulcerative colitis in Asia, including Japan. Here, we report a case of severe Qing-Dai-induced PAH. A 19-year-old woman who has been taking Qing-Dai for 8 months was admitted for exertional dyspnea. Her mean pulmonary artery pressure dramatically improved from 72 to 18 mmHg with Qing-Dai discontinuation and PAH-specific therapy. After 6 years of onset, she had not relapsed with PAH with PAH-specific therapy.

Analysis of factors related to cognitive impairment in a community-based, complete enumeration survey in Japan: the Nakayama study.

BACKGROUND: The number of patients with cognitive disorders is rapidly increasing in the world, becoming not only a medical problem, but also a social problem. There have been many reports that various factors are associated with cognitive dysfunction, but the factors have not yet been fully identified. This was a community-based complete enumeration study which aimed to identify risk and protective factors for dementia. METHODS: The first phase included all residents aged 65 years or older in a town in Japan. They completed many examinations, such as living conditions questionnaires, physical examination, Mini-Mental State Examination, and brain magnetic resonance imaging. The participants with suspected cognitive impairment underwent additional examinations for detailed evaluation in the second phase. Statistical analysis was performed to identify risk and protective factors for dementia after all participants were diagnosed. RESULTS: There were 927 participants in the baseline evaluation; 611 (65.9%) were healthy, 165 (17.8%) had mild cognitive impairment (MCI), and 151 (16.3%) had dementia. The age-standardised prevalence of dementia was 9.5%. Statistical analyses for amnestic MCI and Alzheimer's disease showed that risk factors for cognitive decline were diabetes mellitus, low activities of daily living, and living alone, and that protective factors were history of exercise and drinking habit. CONCLUSION: The present findings suggest that several lifestyle-related diseases and factors are associated with cognitive decline. These results support similar findings from previous studies and will be helpful for preventing dementia in the future.

SPERM FACTORS AND EGG ACTIVATION: Divergent sperm factors for egg activation in amphibian fertilization.

Mature amphibian eggs arrested at meiotic metaphase II must undergo activation to initiate embryonic development soon after fertilization. Fertilizing sperm provide eggs with a signal that induces egg activation, and an increase in intracellular Ca2+ concentration in the egg cytoplasm (a Ca2+ rise) is the most important signal for this initiation. The sperm transmits the signal for the Ca2+ rise, known as the sperm factor, which is divergent between anurans and urodeles. In monospermic anurans, the sperm transmits the signal through a receptor on the egg membrane, causing a single rapid Ca2+ rise. Sperm matrix metalloproteinase-2 is a potential candidate for the receptor-mediated sperm factor in anurans. In physiologically polyspermic urodeles, multiple slower Ca2+ rises are caused by a soluble sperm factor (sperm-specific citrate synthase) which is transferred to the egg cytoplasm after sperm-egg fusion. We discuss the molecular mechanisms of egg activation in amphibian fertilization, focusing on recent progress in characterizing these sperm factors and their divergence during the evolution of tetrapod vertebrates.

Impact of Gestational Haloperidol Exposure on miR-137-3p and Nr3c1 mRNA Expression in Hippocampus of Offspring Mice.

BACKGROUND: Schizophrenia is a mental disorder caused by both environmental and genetic factors. Prenatal exposure to antipsychotics, an environmental factor for the fetal brain, induces apoptotic neurodegeneration and cognitive impairment of offspring similar to schizophrenia. The aim was to investigate molecular biological changes in the fetal hippocampus exposed to haloperidol (HAL) by RNA expression as a model of the disorder. METHODS: HAL (1 mg/kg/d) was administered to pregnant mice. Upregulated and downregulated gene expressions in the hippocampus of offspring were studied with RNA-sequencing and validated with the qPCR method, and micro-RNA (miR) regulating mRNA expressional changes was predicted by in silico analysis. An in vitro experiment was used to identify the miRNA using a dual-luciferase assay. RESULTS: There were significant gene expressional changes (1370 upregulated and 1260 downregulated genes) in the HAL group compared with the control group on RNA-sequencing analysis (P < .05 and q < 0.05). Of them, the increase of Nr3c1 mRNA expression was successfully validated, and in silico analysis predicted that microRNA-137-3p (miR-137-3p) possibly regulates that gene's expression. The expression of miR-137-3p in the hippocampus of offspring was significantly decreased in the first generation, but it increased in the second generation. In vitro experiments with Neuro2a cells showed that miR-137-3p inversely regulated Nr3c1 mRNA expression, which was upregulated in the HAL group. CONCLUSIONS: These findings will be key for understanding the impact of the molecular biological effects of antipsychotics on the fetal brain.

Clozapine Treatment Is Associated With Higher Prescription Rate of Antipsychotic Monotherapy and Lower Prescription Rate of Other Concomitant Psychotropics: A Real-World Nationwide Study.

BACKGROUND: Although clozapine is effective for treatment-resistant schizophrenia (TRS), the rate of clozapine prescription is still low. Whereas antipsychotic monotherapy is recommended in clinical practice guidelines, the rate of antipsychotic polypharmacy is still high. There is little evidence on whether a clozapine prescription influences changes in the rate of monotherapy and polypharmacy, including antipsychotics and other psychotropics. We therefore hypothesized that the rate of antipsychotic monotherapy in patients with TRS who were prescribed clozapine would be higher than that in patients with schizophrenia who were not prescribed clozapine. METHODS: We assessed 8306 patients with schizophrenia nationwide from 178 institutions in Japan from 2016 to 2019. We analyzed the psychotropic prescription data at discharge in patients diagnosed with TRS and with no description of TRS (ND-TRS) based on the diagnosis listed in the discharge summary. RESULTS: The rate of antipsychotic monotherapy in the TRS with clozapine group (91.3%) was significantly higher than that in the TRS without clozapine group (45.9%; P < 2.0 × 10-16) and the ND-TRS without clozapine group (54.7%; P < 2.0 × 10-16). The rate of antipsychotic monotherapy without any other concomitant psychotropics in the TRS with clozapine group (26.5%) was significantly higher than that in the TRS without clozapine group (12.6%; P = 1.1 × 10-6) and the ND-TRS without clozapine group (17.0%; P = 5.9 × 10-6). CONCLUSIONS: Clozapine prescription could be associated with a high rate of antipsychotic monotherapy. Patients will benefit from the correct diagnosis of TRS and thus from proper clozapine prescription.

Expression of overadaptation in children through drawing a man as a projective measure: a community sample study.

BACKGROUND: Overadaptation, the behavior of individuals who follow the expectations of others as perfectly as possible, is often observed and related to maladjustment, school refusal, and physical symptoms; however, no method has been proposed yet to assess the overadaptive tendency. This study evaluated the efficacy of the Goodenough Draw-a-Man (DAM) test as a projective measure of overadaptation in children. METHODS: Eighty children (36 boys, 44 girls), aged 6-8 years, were assessed for their ability to draw a man using the DAM test. Class teachers were asked to assess whether each child was overadapting. The total and subscale DAM scores and pass rates were compared between children with a teacher-assessed tendency for overadaptation and control children, separately for girls and boys. RESULTS: The mean total DAM score was significantly higher for girls versus boys for both the overadapting children and controls. For boys, no significant differences on the total and subscale DAM scores were noted between the overadapting boys and controls. Conversely, for girls, total and three subscale DAM scores (Mouth/Nose/Ears, Hair, Fingers) were significantly higher in the overadapting girls versus controls. Moreover, for girls, the DAM pass rates on five items (ratio of head; ears present; position and shape of nose; depiction of hair, not to see the scalp; details of fingers) were higher in the overadapting girls versus controls. CONCLUSIONS: The DAM test could identify the overadaptive tendencies of girls aged 6-8 years.

Secular trends in the prevalence of dementia based on a community-based complete enumeration in Japan: the Nakayama Study.

BACKGROUND: The number of dementia patients is increasing worldwide, especially in Japan, which has the world's highest ageing population. The increase in the number of older people with dementia is a medical and socioeconomic problem that needs to be prevented, but the actual situation is still not fully understood. METHODS: Four cross-sectional studies on dementia were conducted in 1997, 2004, 2012, and 2016 for complete enumeration of all residents aged 65 years and older. We examined the secular trends in the prevalence of all-cause dementia, Alzheimer's disease (AD), vascular dementia (VaD), and other/unclassified dementia. RESULTS: The age-standardised prevalence of all-cause dementia significantly increased (4.5% in 1997, 5.7% in 2004, 5.3% in 2012, 9.5% in 2016; P for trend <0.05). Similar trends were observed for AD (1.7%, 3.0%, 2.5% and 4.9%, respectively; P for trend <0.05) and other/unclassified dementia (0.8%, 1.0%, 1.0% and 2.2%, respectively; P for trend <0.05), whereas no significant change in VaD was seen (2.1%, 1.8%, 1.8%, 2.4%, respectively; P for trend = 0.77). The crude prevalence of all-cause dementia and AD increased from 1997 to 2016 among participants aged 75-79 years and ≥85 years (all P for trend <0.05). Similar trends were observed for other/unclassified dementia among participants aged ≥80 years (all P for trend <0.05), but not in VaD. CONCLUSIONS: The prevalence of dementia has increased beyond the ageing of the population, suggesting that factors in addition to ageing are involved in the increase in the number of older people with dementia. To control the increase in the number of older people with dementia, elucidation of secular trends in the incidence, mortality, and prognosis of dementia as well as the factors that promote and protect against dementia, and development of preventive strategies are necessary.

Effects of AGXT2 variants on blood pressure and blood sugar among 750 older Japanese subjects recruited by the complete enumeration survey method.

BACKGROUND: Alanine:glyoxylate aminotransferase 2 (AGXT2; EC 2.6.1.44) is the only enzyme that degrades the R-form of 3-aminoisobutyrate, an intermediate metabolite of thymine. AGXT2, as well as diaminoarginine dimethylaminohydrolase 1 (DDAH1; EC 3.5.3.18), works as an enzyme that degrades asymmetric dimethylarginine (ADMA), which competitively inhibits the nitric oxide synthase family. Thus, these two enzyme activities may change vascular vulnerability for a lifetime via the nitric oxide (NO) system. We investigated the association between vascular conditions and diseases such as hypertension and diabetes mellitus and polymorphisms of these two genes in 750 older Japanese subjects (mean age ± standard deviation, 77.0 ± 7.6 years) recruited using the complete enumeration survey method in the Nakayama study. Demographic and biochemical data, such as blood pressure (BP) and casual blood sugar (CBS), were obtained. Four functional single nucleotide polymorphisms (SNPs; rs37370, rs37369, rs180749, and rs16899974) of AGXT2 and one functional insertion/deletion polymorphism in the promotor region with four SNPs (rs307894, rs669173, rs997251, and rs13373844) of DDAH1 were investigated. Plasma ADMA was also analyzed in 163 subjects. RESULTS: The results of multiple regression analysis showed that a loss of the functional haplotype of AGXT2, CAAA, was significantly positively correlated with BP (systolic BP, p = 0.034; diastolic BP, p = 0.025) and CBS (p = 0.021). No correlation was observed between DDAH1 and either BP or CBS. ADMA concentrations were significantly elevated in subjects with two CAAA haplotypes compared with subjects without the CAAA haplotype (p = 0.033). CONCLUSIONS: Missense variants of AGXT2, but not DDAH1, may be related to vulnerability to vascular diseases such as hypertension and DM via the NO system.

Identification of aberrant innate and adaptive immunity based on changes in global gene expression in the blood of adults with autism spectrum disorder.

BACKGROUND: Autism spectrum disorder (ASD) is characterized as a neurodevelopmental disorder, and one of the main hypotheses regarding its cause is genetic factors. A previous meta-analysis of seven microarray studies and one RNA sequencing (RNA-seq) study using the blood of children with ASD identified dysregulation of gene expressions relevant to the immune system. In this study, we explored changes in global gene expression as the phenotype of ASD in the blood of adults with ASD. METHODS: We recruited an RNA-seq cohort (ASD vs. control; n = 6 each) and a replication cohort (ASD vs. control; n = 19 each) and conducted RNA-seq to explore changes in global gene expression. We then subjected the significantly up- and downregulated genes to gene ontology (GO) and core analyses. Weighted gene correlation network analysis (WGCNA) was performed with all 11,617 genes detected in RNA-seq to identify the ASD-specific gene network. RESULTS: In total, 117 significantly up- and 83 significantly downregulated genes were detected in the ASD compared with the control group, respectively (p < 0.05 and q < 0.05). GO analysis revealed that the aberrant innate and adaptive immunity were more obvious in the 117 upregulated than in the 83 downregulated genes. WGCNA with core analysis revealed that one module including many immune-related genes was associated with the natural killer cell signaling pathway. In the results for the replication cohort, significant changes with same trend found in RNA-seq data were confirmed for MAFB (p = 0.046), RPSAP58 (p = 0.030), and G2MK (p = 0.004). LIMITATIONS: The sample size was relatively small in both the RNA-seq and replication cohorts. This study examined the mRNA expression level, so the interaction between mRNA and protein remains unclear. The expression changes between children and adults with ASD were not compared because only adults with ASD were targeted. CONCLUSIONS: The dysregulated gene expressions confirmed in the blood of adults with ASD were relevant to the dysfunction of innate and adaptive immunity. These findings may aid in understanding the pathogenesis of ASD.

Positional cloning and comprehensive mutation analysis of a Japanese family with lithium-responsive bipolar disorder identifies a novel DOCK5 mutation.

Bipolar disorder (BD) is a severe psychiatric disorder characterized by the recurrence of depressive and manic episodes. Its heritability is high, and many linkage and association studies have been performed. Although various linkage regions and candidate genes have been reported, few have shown sufficient reproducibility, and none have identified the pathogenic genes based on the results of the linkage analysis. To find functional variants that are expected to be rare and have strong genetic effects, we recruited ten healthy individuals, two individuals with unknown status, and six patients with BD or recurrent major depressive disorder (MDD) from a Japanese family consisting of 21 members. We performed a genome-wide linkage analysis using a 100K single-nucleotide polymorphism (SNP) array and microsatellite markers to narrow linkage regions within this family. Subsequently, we performed whole-exome sequencing for two patients with BD to identify genetic mutations in the narrowed linkage regions. Then, we performed co-segregation analysis for DNA variants obtained from the results of the exome sequencing. Finally, we identified a rare heterozygous mutation in exon 31 of DOCK5 (c.3170A>G, p.E1057G). Convergent functional genomics analysis revealed that DOCK5 was listed as one of the biomarkers for mood state and suicidality. Although DOCK5 is still a functionally unknown gene, our findings highlight the possibility of a pathological relationship between BD and DOCK5.

Positional cloning and comprehensive mutation analysis identified a novel KDM2B mutation in a Japanese family with minor malformations, intellectual disability, and schizophrenia.

The importance of epigenetic control in the development of the central nervous system has recently been attracting attention. Methylation patterns of lysine 4 and lysine 36 in histone H3 (H3K4 and H3K36) in the central nervous system are highly conserved among species. Numerous complications of body malformations and neuropsychiatric disorders are due to abnormal histone H3 methylation modifiers. In this study, we analyzed a Japanese family with a dominant inheritance of symptoms including Marfan syndrome-like minor physical anomalies (MPAs), intellectual disability, and schizophrenia (SCZ). We performed positional cloning for this family using a single nucleotide polymorphism (SNP) array and whole-exome sequencing, which revealed a missense coding strand mutation (rs1555289644, NM_032590.4: c.2173G>A, p.A725T) in exon 15 on the plant homeodomain of the KDM2B gene as a possible cause of the disease in the family. The exome sequencing revealed that within the coding region, only a point mutation in KDM2B was present in the region with the highest logarithm of odds score of 2.41 resulting from whole genome linkage analysis. Haplotype analysis revealed co-segregation with four affected family members (IV-9, III-4, IV-5, and IV-8). Lymphoblastoid cell lines from the proband with this mutation showed approximately halved KDM2B expression in comparison with healthy controls. KDM2B acts as an H3K4 and H3K36 histone demethylase. Our findings suggest that haploinsufficiency of KDM2B in the process of development, like other H3K4 and H3K36 methylation modifiers, may have caused MPAs, intellectual disability, and SCZ in this Japanese family.

Sperm MMP-2 is indispensable for fast electrical block to polyspermy at fertilization in Xenopus tropicalis.

Sperm matrix metalloproteinase-2 (MMP-2) is necessary for frog fertilization. Monospermy is ensured by a fast, electrical block to polyspermy mediated by a positive fertilization potential. To determine the role of the MMP-2 hemopexin domain (HPX) in a fast block to polyspermy during fertilization of the frog, Xenopus tropicalis, we prepared mutant frogs deficient in mmp2 gene using the transcription activator-like effector nuclease method. mmp2 ΔHPX (-/-) sperm without MMP-2 protein were able to fertilize wild-type (WT; +/+) eggs. However, polyspermy occurred in some eggs. The mutant sperm generated a normal fertilization potential amounting to 10 mV, and were able to fertilize eggs at 10 mV, at which WT sperm never fertilized. Sensitivity during voltage-dependent fertilization decreased in mutant sperm. This study demonstrates for the first time that the genetic alteration of the MMP-2 molecule in sperm causes polyspermy during fertilization of a monospermic species. Our findings provide reliable evidence that sperm MMP-2 is indispensable for the fast, electrical block to polyspermy during Xenopus fertilization.

Selexipag for Chronic Thromboembolic Pulmonary Hypertension in Japanese Patients　- A Double-Blind, Randomized, Placebo-Controlled, Multicenter Phase II Study.

BACKGROUND: Selexipag is an oral prostacyclin receptor (IP receptor) agonist with a non-prostanoid structure. This study examined its efficacy and safety in Japanese patients with non-operated or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH).Methods and Results:This Phase II study was a randomized, double-blind, placebo-controlled parallel-group comparison. The primary endpoint was a change in pulmonary vascular resistance (PVR) from baseline to week 17. The main analysis involved a per-protocol set group of 28 subjects. The change in PVR (mean±SD) after 17 weeks of treatment in the selexipag group was -104±191 dyn·s/cm5, whereas that in the placebo group was 26±180 dyn·s/cm5. Thus, the treatment effect after 17 weeks of selexipag treatment was calculated as -130±189 dyn·s/cm5(P=0.1553). Although the primary endpoint was not met, for the group not concomitantly using a pulmonary vasodilator the PVR in the selexipag group was significantly decreased compared with placebo group (P=0.0364). The selexipag group also showed improvement in total pulmonary resistance and cardiac index. CONCLUSIONS: Selexipag treatment improved pulmonary hemodynamics in Japanese patients with CTEPH, but PVR did not show a significant difference between the selexipag and placebo groups. (Trial registration: JAPIC Clinical Trials Information [JapicCTI-111667]).

DRD2 methylation to differentiate dementia with Lewy bodies from Parkinson's disease.

OBJECTIVE: The aim was to clarify whether DRD2 methylation changes in leukocytes of dementia with Lewy bodies (DLB) or Parkinson's disease (PD) patients are seen and can be used to discriminate between them. METHODS: Methylation rates were examined in 23 DLB subjects and 23 age- and sex-matched healthy controls and 37 PD patients and 37 age- and sex-matched healthy controls. RESULTS: Significant DRD2 DNA methylation changes were found in leukocytes of DLB and PD patients compared with healthy subjects. Discriminant analysis between DLB and PD using seven CpG sites demonstrated sensitivity and specificity of 83.8% and 90.9%, respectively. None of the CpG sites were associated with sex, age, age of onset, disease duration, and any of the neuropsychological tests in DLB and PD patients. CONCLUSION: This is the first report showing that DRD2 DNA methylation rates in leukocytes were increased in DLB patients and decreased in PD patients. These results may be an important step in understanding epigenetic mechanisms underlying DLB and PD pathogenesis and providing a novel biomarker for discriminating between them.

Prevalence of possible idiopathic normal pressure hydrocephalus in older inpatients with schizophrenia: a replication study.

BACKGROUND: We recently reported that older patients with schizophrenia (SZ) show possible idiopathic normal pressure hydrocephalus (iNPH) more frequently than the general population. In this study, we estimated the prevalence of iNPH in a larger number of older SZ patients and explored useful examination values for diagnosis in the SZ population. METHODS: We enrolled older inpatients with SZ (n = 39, mean age = 68.6 ± 7.7 years) from several psychiatric hospitals in Ehime, Japan and acquired brain imaging data using computed tomography. We evaluated three iNPH symptoms (dementia, gait disturbance, and urinary incontinence). In addition, we combined these data with our previous data to elucidate the relationship between iNPH and characteristics of SZ symptoms. RESULTS: In total, five (12.8%) patients were diagnosed with possible iNPH. Evans' index for patients with iNPH was significantly higher than for those without iNPH (p = 0.002). The number of disproportionately enlarged subarachnoid space hydrocephalus (DESH) findings was significantly higher in patients with iNPH than in those without iNPH (p <  0.001). Using combined data, Drug-Induced Extra-pyramidal Symptoms Scale (DIEPSS) subscales of gait and bradykinesia showed an increasing trend in the SZ with iNPH group. CONCLUSIONS: We reconfirmed that older inpatients with SZ experienced possible iNPH more frequently than the general population. We should pay attention to the DIEPSS subscales of gait and bradykinesia and DESH findings in addition to the three main symptoms of iNPH and Evans' index so as to not miss SZ patients with iNPH.

Prevalence of Internet addiction in Japan: Comparison of two cross-sectional surveys.

BACKGROUND: Internet addiction is a serious problem, and the incidence has increased significantly in recent years. In two cross-sectional studies over a 4-year period, we investigated Internet addiction in adolescents and evaluated the resulting changes in their lives. METHODS: Junior high-school students (aged 12 to 15 years) were assessed in 2014 (survey I) and in 2018 (survey II). They filled out Young's Internet Addiction Test (IAT), the Japanese version of the General Health Questionnaire, and a questionnaire on sleep habits and usage of electric devices. RESULTS: In total, 1,382 students were recruited for the two surveys. The mean IAT score was significantly higher in survey II (36.0 ± 15.2) than in survey I (32.4 ± 13.6) (P < 0.001). The increase in total IAT score indicates that the rate of Internet addiction was significantly higher in 2018 than in 2014. For each subscale of the General Health Questionnaire, social dysfunction scores were significantly lower in survey II than in survey I (P = 0.022). During the weekend, mean total sleep time was 504.8 ± 110.1 min, and the time awake was 08:02 h in survey II; the total sleep time and time awake were significantly longer and later, respectively, in survey II than in survey I (P < 0.001, P = 0.004, respectively). Smartphone use was also significantly higher in survey II than in survey I (P < 0.001). CONCLUSIONS: The prevalence of Internet addiction differed over the 4 years of this study.

The electrical block to polyspermy induced by an intracellular Ca2+ increase at fertilization of the clawed frogs, Xenopus laevis and Xenopus tropicalis.

Polyspermy blocking, to ensure monospermic fertilization, is necessary for normal diploid development in most animals. We have demonstrated here that monospermy in the clawed frog, Xenopus tropicalis, as well as in X. laevis, is ensured by a fast, electrical block to polyspermy on the egg plasma membrane after the entry of the first sperm, which is mediated by the positive-going fertilization potential. An intracellular Ca2+ concentration ([Ca2+ ]i ) at the sperm entry site was propagated as a Ca2+ wave over the whole egg cytoplasm. In the X. tropicalis eggs fertilized in 10% Steinberg's solution, the positive-going fertilization potential of +27 mV was generated by opening of Ca2+ -activated Cl- -channels (CaCCs). The fertilization was completely inhibited when the egg's membrane potential was clamped at +10 mV and 0 mV in X. tropicalis and X. laevis, respectively. In X. tropicalis, a small number of eggs were fertilized at 0 mV. In the eggs whose membrane potential was clamped below -10 mV, a large increase in inward current, the fertilization current, was recorded and allowed polyspermy to occur. A small initial step-like current (IS current) was observed at the beginning of the increase in the fertilization current. As the IS current was elicited soon after a small increase in [Ca2+ ]i , this is probably mediated by the opening of CaCCs. This study not only characterized the fast and electrical polyspermy in X. tropicalis, but also explained that the initial phase of [Ca2+ ]i increase causes IS current during the early phase of egg activation of Xenopus fertilization.