Factors influencing acceptability of final disposal of incinerated ash and decontaminated soil from TEPCO's Fukushima Daiichi nuclear power plant accident.

TEPCO's Fukushima Daiichi nuclear power plant accident prompted extensive decontamination work. The decontaminated soil and incinerated ash generated by the process are scheduled for final disposal by March 2045 outside Fukushima Prefecture. The final disposal is unprecedented worldwide. Clarifying their acceptability will contribute to the final disposal of decontaminated soil and incinerated ash, as well as add knowledge about the perceived risk of low-concentration radioactive waste. A questionnaire survey was conducted to assess the psychological factors influencing final disposal acceptability. The results of the structural equation modeling demonstrated stable results, with risk perception decreasing acceptability, social benefits increasing acceptability, and personal benefits having limited impact. The initiative for the final disposal of decontaminated soil and incinerated ash can facilitate the reconstruction of Fukushima Prefecture after the disaster. Trust and intergenerational expectations are critical factors influencing the acceptability of this disposal. The responses were classified based on the relevance of moral norms using cluster analysis and moral foundations. The influence of each element on acceptability varied depending on the cluster. Trust was identified as the most influential factor in acceptability, regardless of the level of importance placed on moral norms.

Odors associated with neonatal experiences with the dam have enhanced anxiolytic effects in rat.

Odor stimuli are widely reported to promote relaxation and reduce anxiety in humans and rodents. However, it remains unclear if this anxiolytic efficacy can be further enhanced by association with positive experiences. Therefore, we compared the effects of a novel odor to a familiar odor previously paired with a positive experience on anxiety-like behaviors in rats. One group of Wistar-Imamichi female and male pups was exposed to an odor stimulus with their dams during postnatal days (PNDs) 8-12, whereas another control group was exposed to perfused air during the same period. Starting on PND 42, all animals were examined in the open field test (OFT) and elevated plus maze (EPM) test during exposure to scent-free air (vehicle), a novel odor, or the positive-familiar odor from postnatal exposure. In the EPM, female rats entered open arms with all 4 paws (complete entry) more frequently and spent more time on open arms during exposure to the positive-familiar odor than during exposure to air or a novel odor, whereas partial open arm entries with forepaws only were increased during exposure to both novel and positive-familiar odors compared to air. In contrast, male rats demonstrated no significant increase in open arm activity during positive-familiar odor exposure, but did show equally reduced grooming frequency during novel and familiar-positive odor exposure in the OFT. Exposure to positive-familiar odors may be an effective and safe method for anxiety reduction, especially in females.

Effects of repetitive transcranial magnetic stimulation on cerebral glucose metabolism.

OBJECTIVE: To investigate the mechanisms underlying the effect of repetitive transcranial magnetic stimulation (rTMS) on post-stroke hemiplegia, we assessed alterations in cerebral glucose metabolism. METHODS: Five post-stroke hemiplegic patients (three targeted for upper limb impairment and two targeted for lower limb impairment) aged 62.6 ± 6.1 years (mean ± standard deviation) with a duration since stroke onset of 3.5 ± 3.8 years participated in this preliminary study. Cerebral glucose metabolism was measured twice-before and after rTMS with intensive rehabilitation-using positron emission tomography with [18F]fluorodeoxyglucose. The Asymmetry Index (AI) was calculated to assess laterality of metabolism between the lesional and contralesional motor areas. The alteration rates of AI (%ΔAI) were compared between participants in whom rTMS was effective and ineffective. RESULTS: Two of the three upper-limb-targeted patients and one of the two lower-limb-targeted patients showed motor function improvements following rTMS treatment. All three patients who responded to rTMS had improved laterality of cerebral glucose metabolism in motor areas, commonly in the precentral gyrus, with an %ΔAI of approximately 10%. In contrast, the two patients who did not respond to rTMS had no improvements in laterality. CONCLUSIONS: These results suggest for the first time that improved glucose metabolism is associated with improved motor function after a combination of rTMS and intensive rehabilitation.

Measurement of Serum Tenascin-X in Joint Hypermobility Syndrome Patients.

Joint hypermobility syndrome (JHS) (also termed hypermobility type Ehlers-Danlos syndrome, hEDS) is a heritable connective tissue disorder that is characterized by generalized joint hypermobility, chronic pain, fatigue, and minor skin changes. Initially, it was reported that there is a small subset of patients with JHS/hEDS who have haploinsufficiency of tenascin-X (TNX). However, the relationship between TNXB and JHS/hEDS has not been reported at all afterwards. EDS was reclassified into thirteen types in 2017, and the causative gene of JHS/hEDS remained to be identified. Therefore, in this study in order to determine whether JHS/hEDS can be diagnosed by the concentrations of serum form of TNX (sTNX), we measured the concentrations of sTNX in 17 JHS/hEDS patients. The sTNX concentrations in half of the JHS/hEDS patients were significantly lower than those in healthy individuals. No mutations, insertions or deletions were detected in the TNX exon sequence of the JHS/hEDS patients except for one in patient. That patient has a heterozygous mutation. A correlation between sTNX concentration and mutation of the TNXB genomic sequence was not found in the JHS/hEDS patients. These results indicate that the decrease in sTNX concentration could be used as a risk factor for JHS/hEDS.

Kampo, A Japanese Traditional Medicinal System for Psychiatric Conditions: A Narrative Review.

INTRODUCTION: Kampo is a Japanese traditional medicinal system and is represented by unity of mind and body. It is originally based upon Chinese traditional medicine but has uniquely developed in Japan. METHODS: A narrative review on the use of Kampo for psychiatric conditions is provided. RESULTS: Kampo formula is a combination of several crude ingredients; most derive from natural plants and some from animals and minerals. These Kampo formulae are widely prescribed in almost all medical disciplines, including psychiatry, in Japan; they have been used for various psychiatric disorders such as dementia, schizophrenia spectrum disorders, mood disorders, anxiety disorders, and personality disorders. Kampo is a versatile traditional medicine with a variety of positive effects on mental states with relatively benign side effect profiles. Kampo formulae can be adjunctively combined with or substituted for the Western psychotropic drugs, which will provide more treatment options to patients with psychiatric conditions. DISCUSSION: This review summarizes the current knowledge on Kampo for psychiatric conditions, highlighting a paucity of data and a need for further good-quality evidence on these medications.

Temporal order memory of the rat in spontaneous object recognition: effects of number of items, exposure interval, and retention time.

Temporal order memory was analyzed using a spontaneous object recognition (SOR) paradigm in rats. In SOR, animals were allowed to explore freely two or five different objects sequentially in the sample phase, and then, two different objects shown in the sample phase were simultaneously presented, and exploration time of object shown earlier compared with that shown later was regarded as a discrimination index. Here we investigated the effects of (1) number of sample items, (2) sample exposure interval, and (3) retention time between the sample and test phases on temporal order memory in SOR. In experiment 1, rats showed significant discrimination between the objects presented earlier and later under five-item, but not two-item, condition. In experiment 2, using the five-item condition, longer retention time (between sample and test phases) induced lower discrimination and longer sample exposure interval produced higher discrimination. In experiment 3, using the two-item condition, longer sample exposure interval produced higher discrimination and longer retention time tended to make rats' discrimination worse. Taken together, these results indicate that rats' performance in this test paradigm was better with more sample items and longer exposure intervals as well as shorter retention time, suggesting that the familiarity to items and the temporal distance from the present to the occurrence of events affect temporal order memory.

Fear memory consolidation in sleep requires protein kinase A.

It is well established that protein kinase A (PKA) is involved in hippocampal dependent memory consolidation. Sleep is also known to play an important role in this process. However, whether sleep-dependent memory consolidation involves PKA activation has not been clearly determined. Using behavioral observation, animals were categorized into sleep and awake groups. We show that intrahippocampal injections of the PKA inhibitor Rp-cAMPs in post-contextual fear conditioning sleep produced a suppression of long-term fear memory, while injections of Rp-cAMPs during an awake state, at a similar time point, had no effect. In contrast, injections of the PKA activator Sp-cAMPs in awake state, rescued sleep deprivation-induced memory impairments. These results suggest that following learning, PKA activation specifically in sleep is required for the consolidation of long-term memory.

Social enrichment improves social recognition memory in male rats.

The social environment is thought to have a strong impact on cognitive functions. In the present study, we investigated whether social enrichment could affect rats' memory ability using the "Different Objects Task (DOT)," in which the levels of memory load could be modulated by changing the number of objects to be remembered. In addition, we applied the DOT to a social discrimination task using unfamiliar conspecific juveniles instead of objects. Animals were housed in one of the three different housing conditions after weaning [postnatal day (PND) 21]: social-separated (1 per cage), standard (3 per cage), or social-enriched (10 per cage) conditions. The object and social recognition tasks were conducted on PND 60. In the sample phase, the rats were allowed to explore a field in which 3, 4, or 5 different, unfamiliar stimuli (conspecific juveniles through a mesh or objects) were presented. In the test phase conducted after a 5-min delay, social-separated rats were able to discriminate the novel conspecific from the familiar ones only under the condition in which three different conspecifics were presented; social-enriched rats managed to recognize the novel conspecific even under the condition of five different conspecifics. On the other hand, in the object recognition task, both social-separated and social-enriched rats were able to discriminate the novel object from the familiar ones under the condition of five different objects. These results suggest that social enrichment can enhance social, but not object, memory span.

Differential Expression of microRNAs in Severely Calcified Carotid Plaques.

BACKGROUND: We investigated whether microRNA (miRNA) alteration is related to the presence of calcification in carotid plaques. METHODS: We classified 10 plaques from carotid endarterectomy patients into high- and low-calcified plaques based on Agatston calcium scores. A microarray analysis for miRNA profiles was performed, with validation by a miRNA quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The miRNA microarray identified 697 probes; 657 of them were downregulated. We selected the genes that satisfied total gene signal (TGS) >50, |Log2 ratio| > 1 and ≥1 of the following: (1) false discovery rate (FDR) <.05 in the comparison of mean values of logarithmic transformed signals between the groups; (2) .05 ≤ FDR < .1 and showing either high or median for context score+ in miRSearch among the 72 carefully selected genes related to angiogenesis or calcification; and (3) FDR < .1 in the comparison of 10 individual sets of high- and low-calcified plaques. The expression of miRNA validated by qRT-PCR revealed a significant downregulation of hsa-miR-4530, hsa-miR133b, and hsa-miR-1-3p. A Spearman's rank correlation analysis revealed that the logarithmic TGSs for the microarray of hsa-miR-4530 and hsa-miR-133b were significantly inversely correlated with the carotid plaques' calcium scores, and the delta Cq values for the qRT-PCR showed a direct association. CONCLUSIONS: In high-calcified carotid plaques, a specific profile for miRNA may be identified, and the expressions of hsa-miR-4530 and hsa-miR-133b had inverse correlations with the calcium score in the plaques, suggesting that miRNAs may play a modulating role in calcified plaques and plaque stability.

Reduction of quality-adjusted life years (QALYs) in patients with premenstrual dysphoric disorder (PMDD).

PURPOSE: Premenstrual dysphoric disorder (PMDD) refers to the depression that occurs during the premenstrual phase and remits soon after the onset of menses. It affects the quality of life (QOL) of patients with PMDD. Therefore, this preliminary survey from chart recordings aimed to understand the symptom appearance and QOL reduction patterns in patients with PMDD, and to examine the extent of the loss of their quality-adjusted life years (QALYs). METHODS: Participants were 66 untreated female patients with PMDD. Data on symptom appearance and QOL reduction during the menstrual cycle, and the EuroQoL-5D (EQ-5D) scores during the premenstrual phase and immediately after the completion of a menstrual period were collected. RESULTS: The mean EQ-5D score of the 66 patients with PMDD was 0.795 ± 0.120 (range 0.362-0.949), indicating that their expected mean loss of QALYs was about 0.14 years. CONCLUSIONS: If untreated, PMDD is expected to cause a mean loss of QALYs of about 0.14 years. However, on accounting for the period from disease development to menopause, and subtracting the menstruation-free periods such as pregnancy and breastfeeding, patients with untreated PMDD are expected to experience a QALY loss of about 3 years during their lifetime.

Current viewpoints on DSM-5 in Japan.

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) was published in 2013, and its official Japanese version was published in 2014. The Japanese Government uses classifications from the 10th revision of the I nternational C lassification of D iseases (ICD-10) to categorize disorders and determine treatment fees. However, since the publication of the DSM-III, the use of the DSM system has become prevalent in research and educational settings in Japan. In addition to traditional psychiatry, both the ICD and the DSM are taught by many Japanese medical schools, and virtually all clinical research and trials refer to the DSM to define targeted disorders. Amid the current backdrop in which the reputation of the DSM-5 is being established, the editorial board of P sychiatry and C linical N eurosciences has asked Japanese experts across 12 specialties to examine the structure of the DSM-5, including the following categories: Neurodevelopmental Disorders, Schizophrenia Spectrum Disorders, Major Depression, Bipolar Disorders, Obsessive-Compulsive Disorders, Somatic Symptom Disorder, Eating Disorders, Substance-Related and Addictive Disorders, Gender Dysphoria, and Neurocognitive Disorders. Although opinions were only obtained from these selected experts, we believe that we have succeeded, to a certain extent, in presenting views that are representative of each specialty.

Sequencing and expression analyses of the synaptic lipid raft adapter gene PAG1 in schizophrenia.

Disruption of synaptic networks has been advocated in the pathogenesis of psychiatric diseases like schizophrenia. The majority of synaptic proteins involved in neuronal communications are localized in lipid rafts. These rafts form the platform for coordinating neuronal signal transduction, by clustering interacting partners. The PAG1 protein is a transmembrane adaptor protein in the lipid raft signaling cluster that regulates Src family kinases (SFKs), a convergent point for multiple pathways regulating N-methyl-D-aspartate (NMDA) receptors. Reports of de novo missense mutations in PAG1 and SFK mediated reductions in tyrosine phosphorylation of NMDA receptor subunit proteins in schizophrenia patients, point to a putative role in schizophrenia pathogenesis. To evaluate this, we resequenced the entire coding region of PAG1 in Japanese schizophrenia patients (n = 1,140) and controls (n = 1,140). We identified eight missense variants, of which four were previously unreported. Case-control genetic association analysis of these variants in a larger cohort (n = 4,182) showed neither a statistically significant association of the individual variants with schizophrenia, nor any increased burden of the rare alleles in the patient group. Expression levels of PAG1 in post-mortem brain samples from schizophrenia patients and controls also showed no significant differences. To assess the precise role of PAG1 in schizophrenia, future studies with larger sample sizes are needed.

Calcified carotid plaques show double symptomatic peaks according to agatston calcium score.

BACKGROUND: The precise mechanism of carotid calcification formation and its clinical significance including the difference in outcomes compared with coronary artery have not been clearly elucidated yet. We applied the calcium score for analyzing carotid plaque calcification in focus on its relationship with symptoms and discuss the difference in transitional patterns and the clinical outcome in comparison with calcified coronary plaques. METHODS: Multidetector row computed tomography angiography was performed preoperatively to determine the Agatston calcium score, volume score, and Hounsfield values for a total of 330 carotid arteries from 194 patients. Analysis focused on the relation of "the symptomatic rate" to calcium score, volume score, and Hounsfield value as well as the characteristics of calcified plaques and coexisting diseases. The symptomatic rate of carotid artery plaques in each range of the index was calculated as the percentage of the number of carotid arteries with plaques, which elicited symptoms of the contralateral limbs or the ipsilateral retina to the whole number of carotid arteries with plaques within the range. RESULTS: Calcified carotids with low symptomatic rate (<40%) tended to have calcification with significantly high calcium scores, high volume scores and mean/maximum Hounsfield values, high circularities, outer positions, positive remodeling, and carotid bulb/common carotid locations by univariate analysis, whereas high maximum Hounsfield value, high circularity, and outer position of calcification were significant independent predictors of low-symptomatic calcified carotid plaques by multivariate logistic regression analysis. When analyzed by calcium score, the rates for symptomatic carotids showed double peaks at calcium scores around 200-400 and 600-800 with a dip at 400-600. Significant independent predictors of low symptomatic carotid artery were high maximum Hounsfield value (odds ratio [OR], 5.70; P = .005), calcification encircling the carotid perimeter (OR, 7.18; P = .005), and the calcium location in the common carotid artery (OR, 6.62; P = .006) in comparing groups with low (0-400) and medium (400-600) calcium scores, whereas a high volume score (OR, .01; P = .003) alone was a significant independent determinant in the comparison between groups with high (600-1000) and medium calcium scores. CONCLUSIONS: Symptomatic rates of carotid plaque calcification were demonstrated to show double peaks with increasing calcium score and represent different features. Assessment of the 2 calcium-score parts might be helpful for appropriate comprehension of symptomatology and the complex process of carotid plaque calcification. We report a hypothesis for the mechanisms of the 2 different sections.

[Premenstrual Dysphoric Disorder (PMDD)].

Premenstrual dysphoric disorder (PMDD) is categorized as a subclass in depressive disorders of DSM-5. Speaking without fear of misunderstanding, my opinion is that patients with PMDD should be treated with medication, if there is no misdiagnosis as premenstrual syndrome (PMS). For the appropriate treatment of PMDD, it must be diagnosed accurately according to the DSM-5 criteria. The differential diagnosis and treatment of PMDD should be carried out by experienced psychiatrists.

[Spirituality and Resilience in Psychiatric Medicine].

At the end of the twentieth century, the WHO tried to change the definition of health. Until then, the health of a person comprised biological, psychological, and social aspects. At the conclusion of the twentieth century, we understood that happiness required more than just these 3 aspects of health. So, the WHO discussed the addition of a spiritual aspect for the new definition of health. It is difficult to translate spirituality into Japanese. However, spirituality is very important in psychiatric care. For example, people who have spiritual pain or grief of loss experience a need for spiritual care. In the recovery process, the importance of resilience has been reported numerous times. Doctor Mieko Kamiya was an excellent psychiatrist and poet. After she contracted tuberculosis and recuperated alone, she fell into a deep depressive state and spent days of distress. In extreme situations, she had the mysterious experience of having her whole body bathed in light. She felt the presence of a great, natural power. Her spirituality and resilience awakened. So, she recovered to strong health through resilience and spirituality. Strong resilience was induced by spirituality. Spiritual care is important in disasters.

Association of decreased prefrontal hemodynamic response during a verbal fluency task with EGR3 gene polymorphism in patients with schizophrenia and in healthy individuals.

The early growth response 3 (EGR3) gene is an immediate early gene that is expressed throughout the brain and has been suggested as a potential susceptibility gene for schizophrenia (SZ). EGR3 impairment is associated with various neurodevelopmental dysfunctions, and some animal studies have reported a role for EGR3 function in the prefrontal cortex. Therefore, EGR3 genotype variation may be reflected in prefrontal function. By using multi-channel near-infrared spectroscopy (NIRS) in an imaging genetics approach, we tested for an association between the EGR3 gene polymorphism and prefrontal hemodynamic response during a cognitive task in patients with SZ. We assessed 73 chronic patients with SZ and 73 age-, gender-, and genotype-matched healthy controls (HC) who provided written informed consent. We used NIRS to measure changes in prefrontal oxygenated hemoglobin concentration (oxyHb) during the letter version of a verbal fluency task (VFT). Statistical comparisons were performed among EGR3 genotype subgroups (rs35201266, GG/GA/AA). The AA genotype group showed significantly smaller oxyHb increases in the left dorsolateral prefrontal cortex (DLPFC) during the VFT than the GG and GA genotype groups; this was true for both patients with SZ and HC. Our findings provide in vivo human evidence of a significant influence of EGR3 polymorphisms on prefrontal hemodynamic activation level in healthy adults and in patients with SZ. Genetic variation in EGR3 may affect prefrontal function through neurodevelopment. This study illustrates the usefulness of NIRS in imaging genetics investigations on psychiatric disorders.

Genetic association study between the detected risk variants based upon type II diabetes GWAS and psychotic disorders in the Japanese population.

Several epidemiological and genetic studies have suggested that the risk of type II diabetes (T2D) is likely to overlap with the susceptibility to psychotic disorders such as schizophrenia (SCZ) and bipolar disorder (BD). In this study, we aimed to examine the association of single-nucleotide polymorphisms (SNPs) detected in previous T2D genome-wide association studies (GWAS) with SCZ, BD and psychosis (SCZ plus BD). A total of 37 SNPs were selected from the literature. A two-stage analysis was conducted using a first set of screening samples (total N=3037) and a second set of replication samples (N=4950). None of the SNPs showed a significant association to the screening samples after correction for multiple testing. To avoid type II error, we genotyped the top three SNPs in BCL11A, HMG20A and HNF4A showing associations with any of the phenotypes (Puncorrected <0.01) using independent samples to replicate the nominal associations. However, we were unable to find any significant associations based on the screening results (Puncorrected>0.05). Our findings did not support the shared genetic risk between T2D and psychotic disorders in the Japanese population. However, further replication using a larger sample size is required.