NARP-related alterations in the excitatory and inhibitory circuitry of socially isolated mice: developmental insights and implications for autism spectrum disorder.

Background: Social isolation during critical periods of development is associated with alterations in behavior and neuronal circuitry. This study aimed to investigate the immediate and developmental effects of social isolation on firing properties, neuronal activity-regulated pentraxin (NARP) and parvalbumin (PV) expression in the prefrontal cortex (PFC), social behavior in juvenile socially isolated mice, and the biological relevance of NARP expression in autism spectrum disorder (ASD). Methods: Mice were subjected to social isolation during postnatal days 21-35 (P21-P35) and were compared with group-housed control mice. Firing properties in the PFC pyramidal neurons were altered in P35 socially isolated mice, which might be associated with alterations in NARP and PV expression. Results: In adulthood, mice that underwent juvenile social isolation exhibited difficulty distinguishing between novel and familiar mice during a social memory task, while maintaining similar levels of social interaction as the control mice. Furthermore, a marked decrease in NARP expression in lymphoblastoid cell lines derived from adolescent humans with ASD as compared to typically developing (TD) humans was found. Conclusion: Our study highlights the role of electrophysiological properties, as well as NARP and PV expression in the PFC in mediating the developmental consequences of social isolation on behavior.

Blood pressure, pulse rate, and skin temperature during hot-water bathing in real-world settings among community-dwelling older adults: the HEIJO-KYO Study.

BACKGROUND: Home hot-tub bathing substantially increases drowning mortality rates among older adults in Japan. Previous laboratory studies on hemodynamic responses during hot-tub bathing have been inconsistent depending on the thermal conditions. Furthermore, real-world hemodynamic changes that occur during bathing remain poorly understood. This study investigated the association between individual thermal states and hemodynamic parameters during hot-tub bathing among community-dwelling older adults. METHODS: In this cross-sectional study conducted between January 2016 and April 2019, which involved 1,479 older adults (median [range] age, 68 [40-90] years), skin temperature on the abdominal surface was measured every minute. Ambulatory blood pressure and pulse rate were recorded at 15-min intervals for 24 h. Participants underwent simultaneous living room temperature measurements in their homes, and the time and methods of bathing were recorded. Associations between skin temperature and hemodynamic parameters during bathing and between the pre-bath living room temperature and in-bath maximum proximal skin temperature were evaluated using mixed-effects and linear regression models, respectively. RESULTS: A 1 °C increase in skin temperature was significantly associated with a 2.41 mmHg (95% confidence interval [CI]: 2.03-2.79) increase in systolic blood pressure and a 2.99 bpm (95% CI: 2.66-3.32) increase in pulse rate, after adjusting for potential confounders, including age, sex, body mass index, antihypertensive medication use, dyslipidemia, diabetes, and living room and outdoor temperatures. Significant interactions were not observed between sex and skin temperature in relation to systolic blood pressure and pulse rate (P = 0.088 and 0.490, respectively). One standard deviation lower living room temperature before bathing was significantly associated with a 0.41 °C (95% CI: 0.35-0.47) higher maximum skin temperature during bathing. CONCLUSIONS: Our findings suggest that pre-bath cold exposure may increase the skin temperature during hot-tub bathing, possibly resulting in excessive hemodynamic changes. This provides a framework for future interventions that utilize pre-bath thermal conditions and bathing environments to prevent bath-related deaths.

Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior.

Microglia and brain-derived neurotrophic factor (BDNF) are essential for the neuroplasticity that characterizes critical developmental periods. The experience-dependent development of social behaviors-associated with the medial prefrontal cortex (mPFC)-has a critical period during the juvenile period in mice. However, whether microglia and BDNF affect social development remains unclear. Herein, we aimed to elucidate the effects of microglia-derived BDNF on social behaviors and mPFC development. Mice that underwent social isolation during p21-p35 had increased Bdnf in the microglia accompanied by reduced adulthood sociability. Additionally, transgenic mice overexpressing microglial Bdnf-regulated using doxycycline at different time points-underwent behavioral, electrophysiological, and gene expression analyses. In these mice, long-term overexpression of microglial BDNF impaired sociability and excessive mPFC inhibitory neuronal circuit activity. However, administering doxycycline to normalize BDNF from p21 normalized sociability and electrophysiological function in the mPFC, whereas normalizing BDNF from later ages (p45-p50) did not normalize electrophysiological abnormalities in the mPFC, despite the improved sociability. To evaluate the possible role of BDNF in human sociability, we analyzed the relationship between adverse childhood experiences and BDNF expression in human macrophages, a possible proxy for microglia. Results show that adverse childhood experiences positively correlated with BDNF expression in M2 but not M1 macrophages. In summary, our study demonstrated the influence of microglial BDNF on the development of experience-dependent social behaviors in mice, emphasizing its specific impact on the maturation of mPFC function, particularly during the juvenile period. Furthermore, our results propose a translational implication by suggesting a potential link between BDNF secretion from macrophages and childhood experiences in humans.

Loss of myocardial Hey2/Hrt2 function disrupts rightward shift of atrioventricular cushion tissue and causes tricuspid atresia.

BACKGROUND: Endocardial cushion tissue is primordia of the valves and septa of the adult heart, and its malformation causes various congenital heart diseases (CHDs). Tricuspid atresia (TA) is defined as congenital absence or agenesis of the tricuspid valve caused by endocardial cushion defects. However, little is known about what type of endocardial cushion defect causes TA. RESULTS: Using three-dimensional volume rendering image analysis, we demonstrated morphological changes of endocardial cushion tissue in developing Hey2/Hrt2 KO mouse embryos that showed malformation of the tricuspid valve, which resembled human TA at neonatal period. In control embryos, atrioventricular (AV) endocardial cushion tissues showed rightward shift to form a tricuspid valve. However, the rightward shift of endocardial cushion tissue was disrupted in Hey2/Hrt2 KO embryos, leading to the misalignment of AV cushions. We also found that muscular tissue filled up the space between the right atrium and ventricle, resulting in the absence of the tricuspid valve. Moreover, analysis using tissue-specific conditional KO mice showed that HEY2/HRT2-expressing myocardium may physically regulate the AV shift. CONCLUSION: Disruption of rightward cushion movement is an initial cue of TA phenotype, and myocardial HEY2/HRT2 is necessary for the regulation of proper alignment of AV endocardial cushion tissue.

Diagnosing psychiatric disorders from history of present illness using a large-scale linguistic model.

AIM: Recent advances in natural language processing models are expected to provide diagnostic assistance in psychiatry from the history of present illness (HPI). However, existing studies have been limited, with the target diseases including only major diseases, small sample sizes, or no comparison with diagnoses made by psychiatrists to ensure accuracy. Therefore, we formulated an accurate diagnostic model that covers all psychiatric disorders. METHODS: HPIs and diagnoses were extracted from discharge summaries of 2,642 cases at the Nara Medical University Hospital, Japan, from 21 May 2007, to 31 May 31 2021. The diagnoses were classified into 11 classes according to the code from ICD-10 Chapter V. Using UTH-BERT pre-trained on the electronic medical records of the University of Tokyo Hospital, Japan, we predicted the main diagnoses at discharge based on HPIs and compared the concordance rate with the results of psychiatrists. The psychiatrists were divided into two groups: semi-Designated with 3-4 years of experience and Residents with only 2 months of experience. RESULTS: The model's match rate was 74.3%, compared to 71.5% for the semi-Designated psychiatrists and 69.4% for the Residents. If the cases were limited to those correctly answered by the semi-Designated group, the model and the Residents performed at 84.9% and 83.3%, respectively. CONCLUSION: We demonstrated that the model matched the diagnosis predicted from the HPI with a high probability to the principal diagnosis at discharge. Hence, the model can provide diagnostic suggestions in actual clinical practice.

Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior.

Microglia and brain-derived neurotrophic factor (BDNF) are essential for the neuroplasticity that characterizes critical developmental periods. The experience-dependent development of social behaviors-associated with the medial prefrontal cortex (mPFC)-has a critical period during the juvenile period in mice. However, whether microglia and BDNF affect social development remains unclear. Herein, we aimed to elucidate the effects of microglia-derived BDNF on social behaviors and mPFC development. Mice that underwent social isolation during p21-p35 had increased Bdnf in the microglia accompanied by reduced adulthood sociability. Additionally, transgenic mice overexpressing microglia Bdnf-regulated using doxycycline at different time points-underwent behavioral, electrophysiological, and gene expression analyses. In these mice, long-term overexpression of microglia BDNF impaired sociability and excessive mPFC inhibitory neuronal circuit activity. However, administration of doxycycline to normalize BDNF from p21 normalized sociability and electrophysiological functions; this was not observed when BDNF was normalized from a later age (p45-p50). To evaluate the possible role of BDNF in human sociability, we analyzed the relationship between adverse childhood experiences and BDNF expression in human macrophages, a possible substitute for microglia. Results show that adverse childhood experiences positively correlated with BDNF expression in M2 but not M1 macrophages. Thus, microglia BDNF might regulate sociability and mPFC maturation in mice during the juvenile period. Furthermore, childhood experiences in humans may be related to BDNF secretion from macrophages.

Impact of the COVID-19 pandemic on prehospital characteristics and outcomes of out-of-hospital cardiac arrest among the elderly in Japan: A nationwide study.

Aim: To assess the impact of the 2020 coronavirus disease (COVID-19) pandemic on the prehospital characteristics and outcomes of out-of-hospital cardiac arrest (OHCA) in the elderly. Methods: In this population-based nationwide observational study in Japan, 563,100 emergency medical service-unwitnessed OHCAs in elderly (≥65 years) patients involving any prehospital resuscitation efforts were analysed (144,756, 140,741, 140,610, and 136,993 cases in 2020, 2019, 2018, and 2017, respectively). The epidemiology, characteristics, and outcomes associated with OHCAs in elderly patients were compared between 3 years pre-pandemic (2017-2019) and the pandemic year (2020). The primary outcome was neurologically favourable one-month survival. The secondary outcomes were the rate of bystander cardiopulmonary resuscitation (CPR), defibrillation by a bystander, dispatcher-assisted (DA)-CPR attempts, and one-month survival. Results: During the pandemic year, the rates of neurologically favourable 1-month survival (crude odds ratio, 95% confidence interval: 1.19, 1.14-1.25), bystander CPR (1.04, 1.03-1.06), and DA-CPR attempts (1.10, 1.08-1.11) increased, whereas the incidence of public access defibrillation (0.88, 0.83-0.93) decreased. Subgroup analyses based on interaction tests showed that the increased rate of neurologically favourable survival during the pandemic year was enhanced in OHCA at care facilities (1.51, 1.36-1.68) and diminished or abolished on state-of-emergency days (0.90, 0.74-1.09), in the mainly affected prefectures (1.08, 1.01-1.15), and in cases with shockable initial rhythms (1.03, 0.96-1.12). Conclusions: The COVID-19 pandemic increased the bystander CPR rate in association with enhanced DA-CPR attempts and improved the outcomes of elderly patients with OHCAs.

Effects of the 2020 COVID-19 pandemic on outcomes of out-of-hospital cardiac arrest and bystander resuscitation efforts: a nationwide cohort study in Japan.

Background and importance There is limited knowledge about the nationwide impact of the 2020 COVID-19 pandemic in Japan on out-of -hospital cardiac arrest (OHCA) outcomes.Objectives The aim of this study was to investigate the impact of the 2020 COVID-19 pandemic on OHCA outcomes and bystander resuscitation efforts in Japan. Design Retrospective analysis of a nationwide population-based registry of OHCA cases. Settings and participants To conduct this study, we created a comprehensive database comprising 821 665 OHCA cases by combining and reconciling the OHCA database for 835 197 OHCA cases between 2017 and 2020 with another database, including location and time records. After applying exclusion and inclusion criteria, we analysed 751 617 cases.Outcome measures and analysis The primary outcome measure for this study was survival with neurologically favourable outcome (cerebral performance category 1 or 2). We compare OHCA characteristics and outcomes between prepandemic and pandemic years, and also investigated differences in factors associated with outcomes. Results We found that survival with neurologically favourable outcome and the rates of bystander cardiopulmonary resuscitation (CPR) slightly increased in the pandemic year [2.8% vs. 2.9%; crude odds ratio (OR), 1.07; 95% confidence interval (CI), 1.03-1.10; 54.1% vs. 55.3%, 1.05 (1.04-1.06), respectively], although the incidence of public access defibrillation (PAD) slightly decreased [1.8% vs. 1.6%, 0.89 (0.86-0.93)]. Calls for hospital selection by emergency medical service (EMS) increased during the pandemic. Subgroup analysis showed that the incidence of neurologically favourable outcome increased in 2020 for OHCA cases that occurred on nonstate of emergency days, in unaffected prefectures, with noncardiac cause, nonshockable initial rhythm, and during daytime hours. Conclusions During the 2020 COVID-19 pandemic in Japan, survival with neurologically favourable outcome of OHCA patients and bystander CPR rate did not negatively change, despite the decrement in PAD incidence. However, these effects varied with the state of emergency, region, and characteristics of OHCA, suggesting an imbalance between medical demand and supply, and raising concerns about the pandemic.

Association Between Before-bedtime Passive Body Heating and Nocturia During the Cold Season Among Older Adults.

BACKGROUND: Cold exposure induces lower urinary tract symptoms, including nocturia. Cold-induced detrusor overactivity can be alleviated by increasing skin temperature in rats. However, no study has shown an association between passive heating via hot-water bathing and nocturia among humans. METHODS: We included 1,051 Japanese community-dwelling older adults (mean age: 71.7 years) in this cross-sectional study from 2010 to 2014. The number of nocturnal voids was recorded in a self-administered urination diary. Nocturia was defined as ≥2 nocturnal voids. We evaluated bathing conditions in the participants' houses. RESULTS: Hot-water bathing (n = 888) was associated with a lower prevalence of nocturia than no bathing (n = 163), independent of potential confounders, including age, sex, obesity, income, physical activity, diabetes, medication (diuretics, nondiuretic antihypertensives, and hypnotics), depressive symptoms, indoor/outdoor temperature, and day length (odds ratio [OR] 0.68; 95% confidence interval [CI], 0.48-0.97; P = 0.035). Compared with the quartile group with the longest bath-to-bed interval (range: 161-576 min), the second and third quartile groups (range: 61-100 and 101-160 min, respectively) were associated with a lower prevalence of nocturia, after adjusting for water temperature and bathing duration besides the same covariates (OR 0.60; 95% CI, 0.38-0.96; P = 0.031 and OR 0.59; 95% CI, 0.37-0.94; P = 0.025, respectively). CONCLUSION: Hot-water bathing, particularly with a bath-to-bed interval of 61-160 min, was significantly associated with a lower prevalence of nocturia among older adults.

Influence of depression on the association between colder indoor temperature and higher blood pressure.

OBJECTIVES: Cold exposure accounts for more than 7% of all-cause mortality worldwide, and cold-induced blood pressure (BP) elevation and consequent cardiovascular events are partially responsible. For prevention, it is important to identify risk factors for exaggerated temperature-sensitivity of BP but this is not fully understood. This study investigated whether depressive symptoms affect the relationship between indoor temperature and BP. METHODS: We conducted a cross-sectional analysis of 1076 community-based individuals who were at least 60 years of age. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale at a cutoff point of 4/5. We performed ambulatory BP monitoring and indoor temperature measurement on two consecutive days during the cold season in Nara, Japan. RESULTS: When using daytime SBP as a dependent variable, multilevel linear regression analyses showed that lower daytime indoor temperature was significantly associated with higher daytime SBP in the depressive group (n = 216, ß = -0.804, P < 0.001) but not in the nondepressive group (n = 860, ß = -0.173, P = 0.120); moreover, a significant interaction between depression and daytime indoor temperature was observed (P = 0.014). These relationships were independent of potential confounders including age, gender, BMI, medications, and physical activity. Similar results were obtained for morning SBP, nocturnal SBP dipping, and morning BP surge. CONCLUSION: The results suggest that depressive participants are more likely to have cold-induced BP elevation than nondepressive participants. Further longitudinal studies are warranted to determine whether people with depressive symptoms are at a high risk for cold-related cardiovascular events.

Tumor necrosis factor-α expression aberration of M1/M2 macrophages in adult high-functioning autism spectrum disorder.

The etiology of autism spectrum disorder (ASD) is complex, and its pathobiology is characterized by enhanced inflammatory activities; however, the precise pathobiology and underlying causes of ASD remain unclear. This study was performed to identify inflammatory indicators useful for diagnosing ASD. The mRNA expression of cytokines, including tumor necrosis factor-α (TNF-α), was measured in cultured M1 and M2 macrophages from patients with ASD (n = 29) and typically developed (TD) individuals (n = 30). Additionally, TNF-α expression in the monocytes of patients with ASD (n = 7), showing aberrations in TNF-α expression in M1/M2 macrophages and TD individuals (n = 6), was measured. TNF-α expression in M1 macrophages and the TNF-α expression ratio in M1/M2 macrophages were markedly higher in patients with ASD than in TD individuals; however, this increase was not observed in M2 macrophages (M1: sensitivity = 34.5%, specificity = 96.7%, area under the curve = 0.74, positive likelihood ratio = 10.34; ratio of M1/M2: sensitivity = 55.2%, specificity = 96.7%, area under the curve = 0.79, positive likelihood ratio = 16.55). Additionally, TNF-α expression in monocytes did not significantly differ between patients with ASD and TD individuals. In conclusion, further studies on TNF-α expression in cultured macrophages may improve the understanding of ASD pathobiology. LAY SUMMARY: TNF-α expression in differentiated M1 macrophages and TNF-α expression ratio in differentiated M1/M2 macrophages were markedly higher in patients with ASD than in TD individuals, while no difference in TNF-α expression was found in pre-differentiation cells such as monocytes. These measurements allow elucidation of the novel pathobiology of ASD and can contribute to biomarker implementation for the diagnosis of adult high-functioning ASD.

A retrospective study of factors associated with persistent delirium.

BACKGROUND: It has been reported that delirium causes various problems. Many researchers have reported the risk factors associated with the onset of delirium; however, there are few reports focused on persistent delirium. This study aimed to identify the risk factors associated with persistent delirium. METHODS: A total of 573 patients hospitalised in Nara Prefecture General Medical Centre from October 2014 through September 2017 who were referred to the psychiatry consultation service were included in this study. Persistent delirium was defined as delirium lasting for 14 days or more. A retrospective study was carried out based on the patients' records. The relationship between various background factors and persistent delirium was statistically analysed. RESULTS: Of the 573 hospitalised patients, 295 were diagnosed as having delirium. Forty-six patients with persistent delirium and 181 patients with nonpersistent delirium were included in this study. Multivariable logistic regression analyses revealed that male gender, opioid analgesics use, non-opioid analgesics use, and low serum sodium were significantly and independently associated with persistent delirium. Ramelteon or trazodone was used significantly more in persistent delirium, although each use was not significant. CONCLUSION: This is the first study to reveal that male gender and use of analgesics were associated with persistent delirium in general hospital. However, as this is a case-control study and may contain bias, future cohort studies and intervention studies are needed. It is also necessary to investigate the relevance of the 'degree of pain' behind the use of analgesics.

Association between NT-proBNP and nocturia among community-dwelling elderly males and females: A cross-sectional analysis of the HEIJO-KYO study.

AIMS: To investigate the association between B-type natriuretic peptide (BNP) and nocturia among community-dwelling males and females. METHODS: A total of 1096 participants (mean age 71.9 ± 7.1 years, 518 [47.2%] males) were included in the study. The number of nocturnal voids was recorded in a self-reported urination diary, and nocturia was defined as two or more voids per night. Daytime serum concentration of the N-terminal fragment of BNP precursor (NT-proBNP) was measured. Multivariable logistic regression analysis was performed to determine the association between NT-proBNP and nocturia. RESULTS: Nocturia was observed in 23.5% of females and 37.1% of males. Higher NT-proBNP (log pg/ml) was associated with nocturia in both gender groups (females: odds ratio [OR]: 1.67, 95% confidence interval [95% CI], 1.21-2.34, p = .002; males: OR: 1.26, 95% CI, 1.01-1.59, p = .046), independent of confounding variables including night-time blood pressure, mean voided volume, and chronic kidney disease. Although the increase in prevalence of nocturia with higher NT-proBNP was equivalent in both genders, some effect of gender on the relationship between NT-proBNP and nocturia was observed (p = .037). Nocturnal urine volume was also significantly and independently associated with NT-proBNP level (females: ß = 32.9 ml, 95% CI, 5.63-60.2, p = .018; males: ß = 34.6 ml, 95% CI, 9.40-59.9, p = .007). CONCLUSIONS: This study revealed higher serum NT-proBNP is significantly and independently associated with the prevalence of nocturia in both males and females. This is an exploratory cross-sectional study and the analyses are post hoc, so further research works are needed to clarify the causality and clinical value.

Coaxial semi-dipole antenna microwave feeding on electron cyclotron resonance multicharged ion source.

How to produce multicharged ions efficiently on an electron cyclotron resonance ion source (ECRIS) has been investigated at Osaka University. Notably, in recent years, we have focused on heating by new resonance superimposing to electron cyclotron resonance (ECR) plasma. To evaluate its efficiency, we need to know the maximum efficiency of heating with ECR alone, and then, further optimization of ECR heating is required. In consideration of wave propagation, we installed the coaxial semi-dipole antenna on the mirror end along the geometrical axis of the vacuum chamber. We aim at exciting the strength of right-hand polarization (RHP) waves for efficient ECR because RHP waves give rise to ECR. We measure plasma parameters by Langmuir probes and charge state distributions (CSDs) of the extracted ion beams and investigate their qualitative tendencies to incident microwave powers and pressures. We compare the qualitative trend of ion beams and their CSD on microwave power in the case of both the microwave feeding system by the coaxial semi-dipole antenna and that by the rod antenna. Differences between the microwave feeding system before improving and then after upgrading are made clear.

Improving transport and optimizing deceleration of ion beams from electron cyclotron resonance multicharged ion sources.

Electron cyclotron resonance ion sources (ECRISs) are widely applied for ion beam applications, e.g., plasma processing, cancer therapy, and ion engine of an artificial satellite. In our ECRIS, we aim at producing and extracting various ion beams from this device, in particular, Xeq+ ion beams at low energy. In the aerospace engineering field, there are problems of accumulated damages on various component materials caused by low energy of Xe ions from the engine. There are not enough experimental sputtering data for satellite materials at the Xeq+ in the low energy region. Then, we are trying to investigate the sputtering yield experimentally by irradiating the low energy Xe ion beams. To perform this experiment, it is necessary to acquire a certain amount of beam current with low energy. Then, we generate the low energy ion beams by the following steps: First, the ion beams are extracted from the ECRIS at high voltage. Next, these are transported to an ion beam irradiation system (IBIS). Finally, the ion beams are decelerated by the deceleration voltage in the IBIS. We adjusted the beamline. We measure the characteristics of the transport efficiency and decelerated ion beam currents. In this paper, we describe the experimental setup using an existing ECRIS for decelerated heavy ion beams and the results of decelerated ion beam currents.

Upper hybrid resonance heating experiments by X-mode microwaves on electron cyclotron resonance ion source.

We have considered the accessibility condition of electromagnetic and electrostatic waves propagating in an electron cyclotron resonance (ECR) ion source (ECRIS) plasma and then investigated experimentally their correspondence relationships with production of multicharged ions. It has been clarified that there exists an efficient configuration of ECR zones for producing multicharged ion beams and has been suggested that a new resonance, i.e., upper hybrid resonance (UHR), must have occurred. We have been trying to perform advanced experiments with 4-6 GHz X-mode microwaves to the 2.45 GHz ECRIS plasma, and we have succeeded in enhancing the production of multicharged ions by launching X-mode microwaves of these bands. Furthermore, at the same time, we have observed sharp increases in electron energy distribution functions in the ECRIS plasma by means of probe methods. It has been concluded that the UHRs must have occurred when applying multiplex microwaves with their frequencies away from those frequencies for ECR in the ECRIS. In this paper, we will describe in brief the theoretical background and the results of these new experiments.

Improving multipole magnets and background vacuum conditions on electron cyclotron resonance ion sources.

Electron cyclotron resonance ion sources (ECRISs) are used in various fields such as accelerator physics, engineering, cancer therapy, and ion engines in the satellite. We are aiming to improve the production of multicharged ions efficiently at the point of view from the length of multipole magnets and vacuum conditions in the ECRIS. The diameter of the connection pipe between the main chamber and diffusion pump was made larger to improve vacuum conductance. Moreover, the length of multipole magnets with the direction along the geometrical axis in the ECRIS was extended. The effects of these improvements are investigated experimentally to measure the pressure in the vacuum chamber, beam intensity, charge state distributions of extracted ion beams, and plasma parameters. The purity of extracted ion beams and magnetic confinement have been enhanced. These results are expected to have positive effects on the production of various species and synthesized ion beams, e.g., production of iron endohedral fullerene in the future experiments in the ECRIS.

Effects of cross-rearing with social peers on myelination in the medial prefrontal cortex of a mouse model with autism spectrum disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interaction, poor communication skills, and repetitive/restrictive behaviors. Recent studies have indicated that early rehabilitative intervention can alleviate the symptoms of individuals with ASD. However, it remains unknown whether rehabilitative intervention can restore brain structures such as myelin, which generally shows abnormalities in individuals with ASD. Therefore, in the present study, we used a mouse model of ASD (BTBR mice) that demonstrated asocial behaviors and hypomyelination in the medial prefrontal cortex (mPFC) to investigate whether interaction with social peers (C57BL/6J mice) has an effect on myelination. We found that housing with C57BL/6J mice after weaning through adulthood increased the myelin thickness in mPFC, but not in the motor cortex, of BTBR mice. There was no effect of cross-rearing with C57BL/6J mice on axon diameter in mPFC of BTBR mice. This finding suggests that early rehabilitative intervention may alleviate myelin abnormalities in mPFC as well as clinical symptoms in individuals with ASD.

Effects of the mode of re-socialization after juvenile social isolation on medial prefrontal cortex myelination and function.

Social isolation is an important factor in the development of psychiatric disorders. It is necessary to develop an effective psychological treatment, such as cognitive rehabilitation, for children who have already suffered from social isolation, such as neglect and social rejection. We used socially isolated mice to validate whether elaborate re-socialization after juvenile social isolation can restore hypomyelination in the medial prefrontal cortex (mPFC) and the attendant functions manifested in socially isolated mice. While mice who underwent re-socialization with socially isolated mice after juvenile social isolation (Re-IS mice) demonstrated less mPFC activity during exposure to a strange mouse, as well as thinner myelin in the mPFC than controls, mice who underwent re-socialization with socially housed mice after juvenile social isolation (Re-SH mice) caught up with the controls in terms of most mPFC functions, as well as myelination. Moreover, social interaction of Re-IS mice was reduced as compared to controls, but Re-SH mice showed an amount of social interaction comparable to that of controls. These results suggest that the mode of re-socialization after juvenile social isolation has significant effects on myelination in the mPFC and the attendant functions in mice, indicating the importance of appropriate psychosocial intervention after social isolation.

Microglia-derived neuregulin expression in psychiatric disorders.

Several studies have revealed that neuregulins (NRGs) are involved in brain function and psychiatric disorders. While NRGs have been regarded as neuron- or astrocyte-derived molecules, our research has revealed that microglia also express NRGs, levels of which are markedly increased in activated microglia. Previous studies have indicated that microglia are activated in the brains of individuals with autism spectrum disorder (ASD). Therefore, we investigated microglial NRG mRNA expression in multiple lines of mice considered models of ASD. Intriguingly, microglial NRG expression significantly increased in BTBR and socially-isolated mice, while maternal immune activation (MIA) mice exhibited identical NRG expression to controls. Furthermore, we observed a positive correlation between NRG expression in microglia and peripheral blood mononuclear cells (PBMCs) in mice, suggesting that NRG expression in human PBMCs may mirror microglia-derived NRG expression in the human brain. To translate these findings for application in clinical psychiatry, we measured levels of NRG1 splice-variant expression in clinically available PBMCs of patients with ASD. Levels of NRG1 type III expression in PBMCs were positively correlated with impairments in social interaction in children with ASD (as assessed using the Autistic Diagnostic Interview-Revised test: ADI-R). These findings suggest that immune cell-derived NRGs may be implicated in the pathobiology of psychiatric disorders such as ASD.