Risk factors of hikikomori among office workers during the COVID-19 pandemic: A prospective online survey.

The global pandemic of COVID-19 has forced people to restrict their outings. In Japan, self-restraint behavior (SRB) has been requested by the government, and some of those decreasing their outings may shift to pathological social withdrawal; hikikomori. The purpose of this study was to examine the risk factors of hikikomori conducting an online prospective survey. An online survey was conducted in June 2020 and December 2020; (1) SRB-related indicators (degree of SRB, motivation for SRB, stigma and self-stigma toward COVID-19, anxiety and depressive feelings toward COVID-19) and (2) general mental health (hikikomori tendency, depressive symptoms, modern type depression (MTD) tendency, internet addiction) were collected. A cross-lagged effects model was performed to examine the association between these variables. Lack of emotional support and lack of socialization in June 2020 increased isolation in December 2020. Besides, MTD and hikikomori interacted with each other. Interestingly, although hikikomori tendency increased depressive tendencies, SRB itself did not have a significant path on any mental health-related variables. Poor interpersonal relationships, rather than SRB per se, are suggested to be a risk factor for increased isolation among office workers in the COVID-19 pandemic. Appropriate early interventions such as interpersonal or emotional support may prevent the transition to pathological hikikomori. The association between MTD and hikikomori seems to reveal the interesting possibility that MTD is a gateway to increased risk of hikikomori, and that hikikomori is a gateway to MTD as well. Future research is required to elucidate the relationship between hikikomori and MTD.

Complex structure of cytochrome c-cytochrome c oxidase reveals a novel protein-protein interaction mode.

Mitochondrial cytochrome c oxidase (CcO) transfers electrons from cytochrome c (Cyt.c) to O2 to generate H2O, a process coupled to proton pumping. To elucidate the mechanism of electron transfer, we determined the structure of the mammalian Cyt.c-CcO complex at 2.0-Å resolution and identified an electron transfer pathway from Cyt.c to CcO. The specific interaction between Cyt.c and CcO is stabilized by a few electrostatic interactions between side chains within a small contact surface area. Between the two proteins are three water layers with a long inter-molecular span, one of which lies between the other two layers without significant direct interaction with either protein. Cyt.c undergoes large structural fluctuations, using the interacting regions with CcO as a fulcrum. These features of the protein-protein interaction at the docking interface represent the first known example of a new class of protein-protein interaction, which we term "soft and specific". This interaction is likely to contribute to the rapid association/dissociation of the Cyt.c-CcO complex, which facilitates the sequential supply of four electrons for the O2 reduction reaction.

Autism spectrum conditions in hikikomori: A pilot case-control study.

AIM: Hikikomori, a form of pathological social withdrawal, has been suggested to have comorbidity with autism spectrum disorder (ASD). This study aimed to clarify how characteristics of hikikomori are associated with ASD, including undiagnosed autism spectrum conditions (ASC), in clinical settings. METHODS: A total of 416 clinical patients were recruited through the Mood Disorder/Hikikomori Clinic at Kyushu University Hospital. A total of 103 hikikomori cases and 221 clinical controls without hikikomori conditions were extracted using a semi-structured interview, and completed a series of self-rated scales, including the Japanese version of the Autism-Spectrum Quotient (AQ-J). RESULTS: Compared to non-hikikomori controls, hikikomori cases were more likely to have higher autistic tendency based on the AQ-J. The cases showed more severe subjective depressive symptoms based on the self-rated Beck Depression Inventory II, whereas no significant difference was found on interview-based severity evaluation using the Hamilton Depression Rating Scale. Comparison within hikikomori cases based on the AQ-J cut-off score revealed that hikikomori cases with high ASC were significantly more likely to have higher traits of modern-type depression, smaller social networks, and less social support. CONCLUSION: The present data suggest that hikikomori sufferers are more likely to have autistic tendency, and that hikikomori sufferers with high ASC may have much more difficulty in social communication and social interaction. In addition, those with high ASC may also have lower self-esteem and higher complaint tendencies as aspects of modern-type depression traits, which may relate to the occurrence of hikikomori. Thus, evaluating autistic tendencies is important for appropriate interventions in hikikomori. Further investigations should be conducted to validate our pilot findings using structured diagnostic systems of ASD.

Structural basis for specific recognition of core fucosylation in N-glycans by Pholiota squarrosa lectin (PhoSL).

Fucosylation of the N-glycan core via the α1-6 linkage (core fucosylation) is detected in specific types of cancers and related diseases, and thereby serves for a relevant biomarker. The lectin from a mushroom Pholiota squarrosa (PhoSL) shows a clear specificity to core fucosylation, without recognizing those with other types of fucosylation, such as the H type via the α1-2 linkage or the Lewis type via the α1-3 or α1-4 linkage. Here we determined the crystal structure of the PhoSL trimer in complex with a disaccharide fucose(α1-6)N-acetylglucosamine (GlcNAc). In the three sugar-binding pockets of PhoSL, extensive hydrophobic and hydrogen-bonding contacts were formed with the fucose moiety. In contrast, the GlcNAc moiety showed only a few hydrophobic and hydrogen-bonding contacts. To elucidate the mechanism for the specificity, we performed molecular dynamics simulations on this disaccharide and a trisaccharide fucose(α1-6)[GlcNAc(ß1-4)]GlcNAc in complex with PhoSL. It was observed that the GlcNAc corresponding to the outer one of the N-glycan core entered the sugar-binding pocket with the N-acetyl group placed stably at the bottom, forming extensive hydrophobic and hydrogen-bonding interactions. In addition, these glycans adopted unstressed favorable conformations when bound to PhoSL. In contrast, H- and Lewis-types of fucosylated trisaccharides adopting favorable conformations caused inevitable steric hindrance with the steep edge of the binding pocket, when docked with PhoSL. Therefore, the specificity to core fucosylation of PhoSL was achieved by a combination of these preferential and exclusive mechanisms.

Is it possible for short peptide composed of positively- and negatively-charged "hydrophilic" amino acid residue-clusters to form metastable "hydrophobic" packing?

We theoretically and experimentally analyzed a conformational ensemble of a small, characteristic polypeptide consisting of positively- and negatively-charged amino acid residue clusters, (Lys)9(Glu)9(Lys)9, designed based on the supercoiled DNA-recognition (SDR) domain, with the capability of preferentially binding to supercoiled DNA. Advanced molecular dynamics (MD) simulations coupled with a generalized ensemble technique revealed that substantial amounts of ordered, helical structures were present at the boundaries of the Lys and Glu segments in the obtained conformational ensemble. In fact, the helical content of the peptide calculated from our MD simulations was consistent with that estimated from our experimental analysis employing circular dichroism (CD) spectroscopy. The statistical analysis of the structural ensemble revealed the metastable hydrophobic contact clusters, which were stabilized by closely cohesive residue contacts, formed through "hybrid" hydrophobic (methylene groups) and electrostatic (salt bridges) residue contacts. Both short-range and long-range residue contacts were involved in the metastable hydrophobic clusters, constituting the aforementioned local helical conformations and the compact entire structures, respectively. A significant helical propensity was also found in the (Lys)n and (Glu)m boundaries of other conventional protein structures deposited in the Protein Data Bank (PDB), thus indicating the generality of this conformational trend that has been identified herein.

Development and validation of the 22-item Tarumi's Modern-Type Depression Trait Scale: Avoidance of Social Roles, Complaint, and Low Self-Esteem (TACS-22).

AIM: Understanding premorbid personality is important, especially when considering treatment selection. Historically, the premorbid personality of patients with major depression in Japan was described as Shuchaku-kishitsu [similar to Typus melancholicus], as proposed by Shimoda in the 1930s. Since around 2000, there have been increased reports in Japan of young adults with depression who have had premorbid personality differing from the traditional type. In 2005, Tarumi termed this novel condition 'dysthymic-type depression,' and more recently the condition has been called Shin-gata/Gendai-gata Utsu-byo [modern-type depression (MTD)]. We recently developed a semi-structured diagnostic interview to evaluate MTD. Development of a tool that enables understanding of premorbid personality in a short time, especially at the early stage of treatment, is desirable. The object of this study was to develop a self-report scale to evaluate the traits of MTD, and to assess the scale's psychometric properties, diagnostic accuracy, and biological validity. METHODS: A sample of 340 participants from clinical and community settings completed measures. Psychometric properties were assessed with factor analysis. Diagnostic accuracy of the MTD traits was compared against a semi-structured interview. RESULTS: The questionnaire contained 22 items across three subscales, thus we termed it the 22-item Tarumi's Modern-Type Depression Trait Scale: Avoidance of Social Roles, Complaint, and Low Self-Esteem (TACS-22). Internal consistency, test-retest reliability, and convergent validity were all satisfactory. Among patients with major depression, the area under the curve was 0.757 (sensitivity of 63.1% and specificity of 82.9%) and the score was positively correlated with plasma tryptophan. CONCLUSION: The TACS-22 possessed adequate psychometric properties and diagnostic accuracy in an initial sample of Japanese adults. Additional research on its ability to support clinical assessment of MTD is warranted.

Child and adolescent psychiatry in the Far East: A 5-year follow up on the Consortium on Academic Child and Adolescent Psychiatry in the Far East (CACAP-FE) study.

AIM: Data pertaining to child and adolescent psychiatry (CAP) training systems are limited as extant research has mostly been derived from one-time data collection. This 5-year follow-up survey collects updated information on CAP training systems in the Far East, allowing for the tracking of system changes over the past 5 years. METHODS: Data were obtained from 18 countries, or functionally self-governing areas, in the Far East, 17 of which were also included in the original study. An online questionnaire was completed by leading CAP professionals in each country. Questions were expanded in the present study to capture the contents of CAP training. RESULTS: When compared to data from the original study, there has been progress in CAP training systems in the last 5 years. Specifically, there has been an increase in the number of countries with CAP training programs and national guidelines for the training. In addition, the number of CAP departments/divisions affiliated with academic institutions/universities has increased. Findings from 12 of 18 countries in the present study provide data on clinical contents. All informants of the present study reported the need for more child and adolescent psychiatrists and allied professionals. CONCLUSION: Despite progress in CAP training systems over the last 5 years, the need for more professionals in child and adolescent mental health care in all the relevant areas in this region have yet to be adequately addressed. Continued national efforts and international collaborations are imperative to developing and sustaining new CAP training systems while facilitating improvements in existing programs.

Prevalence rate of Internet addiction among Japanese college students: Two cross-sectional studies and reconsideration of cut-off points of Young's Internet Addiction Test in Japan.

AIM: Due to variation in estimates of the prevalence of Internet addiction (IA) in prior research, we conducted two cross-sectional studies over 2 years investigating the prevalence rate of IA in college students in Japan and reconsidered appropriate cut-off points of a self-rating scale to screen possible IA. METHODS: This study was composed of two parts: survey I in 2014 and survey II in 2016, which were conducted in the same schools with an interval of 2 years. The study questionnaire included questions about demographics and Internet use, and Young's Internet Addiction Test (IAT). Additionally, the subjects in survey II were asked about self-reported IA. RESULTS: There were 1005 respondents in total with a mean age (± SD) of 18.9 ± 1.3 years. The mean IAT scores remained stable between 2014 and 2016: 45.2 ± 12.6 in survey I and 45.5 ± 13.1 in survey II (overall mean IAT score of 45.4 ± 13.0). With respect to self-reported IA in survey II, a total of 21.6% admitted to having IA (score of 5 or 6 on a 6-point Likert scale). We categorized these subjects as IA, and the remainder as non-IA. The mean IAT score showed a significant difference between these two groups (57.8 ± 14.3 vs 42.1 ± 10.7, P < 0.001). CONCLUSION: The severity of IA symptoms among Japanese college students has appeared stable in recent years, with mean IAT scores of over 40. Our results suggest that a screening score cut-off of 40 on the IAT could be reconsidered and that 50 might be proposed for the cut-off.

The usefulness of combined brain perfusion single-photon emission computed tomography, Dopamine-transporter single-photon emission computed tomography, and 123 I-metaiodobenzylguanidine myocardial scintigraphy for the diagnosis of dementia with Lewy bodies.

BACKGROUND: Current diagnostic criteria recommend neuroimaging as a diagnostic support tool for the clinical diagnosis of dementia with Lewy bodies (DLB). Because DLB causes characteristic impairments and disabilities, such as neuroleptic hypersensitivity, which may significantly increase morbidity and mortality, its prompt and correct diagnosis is very important. The aim of this study was to evaluate the extent to which diagnostic accuracy can be increased by using different combinations of brain perfusion single-photon emission computed tomography (bp-SPECT), 123 I-metaiodobenzylguanidine myocardial scintigraphy (MIBG scintigraphy), and DAT-SPECT. Taking finances and patient burden into consideration, we compared the tests to determine priority. METHODS: Thirty-four patients with probable DLB (75.0 ± 8.3 years old; 14 men, 20 women) underwent bp-SPECT, MIBG scintigraphy, and DAT-SPECT. RESULTS: Our comparison of three functional imaging techniques indicated that MIBG scintigraphy (79%) and Dopamine-transporter (DAT) SPECT (79%) had better sensitivity for characteristic abnormalities in DLB than bp-SPECT (53%). The combination of the three modalities could increase sensitivity for diagnosis of DLB to 100%. Additionally, the ratio of patients with rapid eye movement sleep behaviour disorder was significantly higher in the positive finding group on MIBG scintigraphy than in the negative finding group. CONCLUSIONS: In terms of stand-alone diagnostic means, priority should be placed on MIBG scintigraphy or DAT-SPECT for the diagnosis of DLB. However, our results suggest that the combination of bp-SPECT, MIBG scintigraphy, and DAT-SPECT increased the accuracy of the clinical diagnosis of DLB.

[Gender Dysphoria in Children in Clinical Practice of Child and Adolescent Psychiatry].

In Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), Gender dysphoria (GD) is defined as a marked incongruence between one's experienced/expressed gender and assigned gender. Clinical pictures of GD in children show marked diversity. Because of their limited ability to express themselves verbally, children with GD might not be able to describe their discomfort or distress about this incongruence. In contrast to GD in adulthood, GD in children could be alleviated in the natural course. Thus, the clinical diagnosis of GD in children should be made carefully. Distortion of gender identity is equal to prominent confusion of identity, and has a huge psychological burden on children with GD. In addition to the distress due to dysphoria about gender, children with GD could suffer from bullying at school, loneliness among school peers or even in their family, and feelings of disgust about their physical appearance that could cause decreased self-esteem and a sense of worthlessness. In 2015, the Ministry of Education, Culture, Sports, Science and Technology (MEXT) in Japan encouraged all school teachers to provide appropriate support at school to sexual minor- ity students, including students with GD. Furthermore, MEXT published a manual for school teachers to promote necessary interventions for such students at school. There are several papers reporting child cases of GD and comorbid psychiatric disorders. Among them, autism spectrum disorder (ASD) is one of the common comorbidities. Reflecting these conditions, recent review articles discuss possible associations between GD and ASD. In this paper, based on the first author's clinical experience, we describe the clinical symp- toms and diagnosis of GD in children, the relationship between GD and ASD, gender-related manifestations observed in ASD, and practical support for children with GD entering primary school.

[A Questionnaire-based Study of Child Psychiatrists and Clinical Psychologists Regarding and Support for Children with Gender Identity Disorder and Sexual Problems].

In 2010, the Ministry of Education, Culture, Sports, Science and Technology (MEXT) in Japan strongly recommended that students with gender identity disorder (GID) who had behavioral health concerns should consult a professional in their schools. Furthermore, in 2015, MEXT subsequently announced that it is important for sexual minority students, including students with GID, to receive more support from professionals through cooperation with medical institutions. However, there has been no nationwide clinical research done on sexual minority youth, so little is known about how to optimally care for them in medical practice. This study assessed the current status of medical care for children and adolescents with GID and other atypical sexual development. The authors surveyed certifying physicians and councilors (315 people in total) of The Japanese Society for Child and Adolescent Psychiatry. The question obtained basic demographic and practice information and allowed for free responses on topics such as opinion on consultation and medical care for GID and atypical sex- ual development in childhood and adolescence. One hundred twenty-seven, or 40.3%, of those surveyed responded. The average number of years of total clinical experience was 23.9, and the average number of years of child psychiatric clinical experience was 18.8 years. The number of child psychiatrists who provided con- sultation for GID and other sexual development including transvestism and gender dysphoria were 88 (68.5%) and 105 (81.9%), respectively. The consultants' most frequent clients, in descending order, were: individuals, parents, and school officials. Seventy-four (57.5%) child psychiatrists provide medical care for patients with GID. In the preschool and elementary school age groups, consultants served many more (assignment) males than (assignment) females with GID, whereas in the higher elementary school and later ages, consultants served more females than males with GID equally often. In junior high school and later ages, consultants served more females than males with GID. Eighty-seven (67.7%) of the child psychiatrists provided medical care for patients with other sexual development. Before and during the mid- dle elementary school ages and in the high school ages, consultants served more males than females with other typical development, whereas in higher grade elementary and junior high school ages, consultants served more females than males with other typical development. The free response sections revealed a diversity of opinions, clinical course, and cooperation with other institutions. At present, among child psychiatrists, there are many different perspectives on clinical care for GID and other sexual development. Therefore, it will be necessary to systematically examine current scientific evidence and to establish consensus on best practices for clinical management.

[The International Study of Burnout Syndrome among Psychiatric Trainees (BoSS International) : Findings from Statistical Analysis of the Japanese Data (BoSS Japan)].

BACKGROUND: Burnout is a psychological condition that may occur after being exposed to excessive and prolonged work-related stresses. Previous studies have demonstrated that the rate of burnout among physicians may be higher compared to other occupations ; and espe- cially psychiatric trainees would have a higher risk of burnout because of limited clinical expe- rience, the burden of heavy duties and longer work-hours etc. In this study, we report the findings from Japanese data obtained as part of the international study of burnout syndrome among psychiatric trainees (BoSS International). METHODS: This study was initiated by members of the European Federation of Psychiatric Trainees (EFPT) and the European Psychiatric Association-European Early Career Psychia- trists (EPA-EECP). The total number of participating nations was 22 countries. A national coordinator recruited study collaborators all over Japan and psychiatric trainees working at their medical institutes were invited to participate in BoSS International by e-mail. The sub- jects were requested to answer the on-line questionnaire anonymously. Consent was obtained when making a list of potential participants at each institute and reconfirmed on the first page of the on-line questionnaire. Answering the questionnaire was deemed to constitute consent. RESULTS: Total number of participants to BoSS International was 7,525 from 22 countries and regions. Of them, 1,980 psychiatric trainees fully completed answering the questionnaire (response rate (RR) 26.0%) including 95 Japanese trainees (RR 41.5%). The mean age of 95 Japanese psychiatric trainees (male rate 67.4%) enrolled in BoSS International was 31.8?4.8 year-old. Their mean clinical experience was 2.9 ?4.4 years. The mean weekly working hours were 72.3?27.1, which was the longest of the 22 participating countries/regions ; while weekly clinical supervision by a mentor was only 3.8?9.0 hours. Regarding the severity of burnout, assessed by using the Maslach Burnout Inventory-General Survey (MBI-GS) consisting of three factors (emotional exhaustion, cynicism, and low sense of professional efficacy): 41 Japanese psychiatric trainees (42.0%) meet the criteria of severe burnout syndrome in this study ; with emotional exhaustion scores of 2.20 and higher, and cynicism of 2.00 and higher. Signifi- cant differences were found on the PHQ-9 score and mean length of supervision between those participants with presence and absence of severe burnout syndrome by using Student's t-test. CONCLUSION: Statistical analyses of the whole data (n=1,980) revealed that the risk of burnout was higher for trainees who were younger, without children, and had not opted for psychiatry as a first career choice. Further analyses after adjustment for socio-demographic characteristics and country difference still demonstrated severe burnout was associated with long working hours, less supervision, and not having regular rest. The analyses of Japanese data showed similar tendencies, although statistical significance was not observed. Burnout among psychiatry trainees may be linked to drop-out from the training program and malprac- tice in clinical settings. We should be aware of the higher risk of burnout in residents and the importance of regular and sufficient supervision to prevent burnout.

Internet addiction and self-evaluated attention-deficit hyperactivity disorder traits among Japanese college students.

AIM: Internet addiction (IA), also referred to as Internet use disorder, is a serious problem all over the world, especially in Asian countries. Severe IA in students may be linked to academic failure, attention-deficit hyperactivity disorder (ADHD), and forms of social withdrawal, such as hikikomori. In this study, we performed a survey to investigate the relation between IA and ADHD symptoms among college students. METHODS: Severity of IA and ADHD traits was assessed by self-report scales. Subjects were 403 college students (response rate 78%) who completed a questionnaire including Young's Internet Addiction Test (IAT) and the Adult ADHD Self-Report Scale-V1.1. RESULTS: Out of 403 subjects, 165 were male. The mean age was 18.4 ± 1.2 years, and mean total IAT score was 45.2 ± 12.6. One hundred forty-eight respondents (36.7%) were average Internet users (IAT < 40), 240 (59.6%) had possible addiction (IAT 40-69), and 15 (3.7%) had severe addiction (IAT ≥ 70). Mean length of Internet use was 4.1 ± 2.8 h/day on weekdays and 5.9 ± 3.7 h/day on the weekend. Females used the Internet mainly for social networking services while males preferred online games. Students with a positive ADHD screen scored significantly higher on the IAT than those negative for ADHD screen (50.2 ± 12.9 vs 43.3 ± 12.0). CONCLUSION: Our results suggest that Internet misuse may be related to ADHD traits among Japanese youth. Further investigation of the links between IA and ADHD is warranted.

Survey of the relationship between internet addiction and social withdrawal (HIKIKOMORI) in Japan.

PURPOSE: The Internet was originally designed to facilitate communication and research activities.'However, there has been a dramatic increase in the use of the Internet in recent years for commerce, education, and entertainment, including video games. Internet addiction as.a phenomena has been described by researchers as excessive or compulsive use of computers that interferes with daily life. Hikikomori (social withdrawal) -has increasingly become a problem in Japan and has been hypothesized to be ,related to internet, addiction. Particularly amongst students, problematic internet use may be a major factor of social withdrawal. We conducted a survey of internet addiction. and social- withdrawal among college students and corhpany workers to examine this hypothesis. METHODS: Subjects were 63 university students and 56 company workers. To examine the relationship between internet addiction and social withdrawal, we administered the Internet Addiction Test (IAT) and the UCLA Loneliness Scale (ULS), a measure of social isolation, to all subjects. RESULTS: Students tended to score higher than workers on the IAT (Student u = 36.3, Worker u = 31.1, p<0.05). For students considered addictive internet users, we found a significant correlation between the ULS and the IAT (r=0.549,. p<0.05); suggesting that social isolation and internet addiction are associated with each other. Workers tended to score higher on the ULS than students (Worker p =40.4, Student u =37.5, p<0.05). For workers .who were not addictive internet users, we found a'mild, negative correlation between the ULS and the IAT (r=- 0.285, p<0.05), suggesting that use of the internet for workers was not a compensatory behavior. CONCLUSIONS: Based upon the IAT, we found that more students than workers reported problems with internet use. Based upon.the ULS, more workers reported feelings of loneliness than students. Workers' loneliness did not appear to be related to their use of the internet, but amongst students with internet addiction, loneliness appeared to be associated with internet use.

Effective pumping proton collection facilitated by a copper site (CuB) of bovine heart cytochrome c oxidase, revealed by a newly developed time-resolved infrared system.

X-ray structural and mutational analyses have shown that bovine heart cytochrome c oxidase (CcO) pumps protons electrostatically through a hydrogen bond network using net positive charges created upon oxidation of a heme iron (located near the hydrogen bond network) for O2 reduction. Pumping protons are transferred by mobile water molecules from the negative side of the mitochondrial inner membrane through a water channel into the hydrogen bond network. For blockage of spontaneous proton back-leak, the water channel is closed upon O2 binding to the second heme (heme a3) after complete collection of the pumping protons in the hydrogen bond network. For elucidation of the structural bases for the mechanism of the proton collection and timely closure of the water channel, conformational dynamics after photolysis of CO (an O2 analog)-bound CcO was examined using a newly developed time-resolved infrared system feasible for accurate detection of a single C=O stretch band of α-helices of CcO in H2O medium. The present results indicate that migration of CO from heme a3 to CuB in the O2 reduction site induces an intermediate state in which a bulge conformation at Ser-382 in a transmembrane helix is eliminated to open the water channel. The structural changes suggest that, using a conformational relay system, including CuB, O2, heme a3, and two helix turns extending to Ser-382, CuB induces the conformational changes of the water channel that stimulate the proton collection, and senses complete proton loading into the hydrogen bond network to trigger the timely channel closure by O2 transfer from CuB to heme a3.

A novel ab initio identification system of transcriptional regulation motifs in genome DNA sequences based on direct comparison scheme of signal/noise distributions.

A novel ab initio parameter-tuning-free system to identify transcriptional factor (TF) binding motifs (TFBMs) in genome DNA sequences was developed. It is based on the comparison of two types of frequency distributions with respect to the TFBM candidates in the target DNA sequences and the non-candidates in the background sequence, with the latter generated by utilizing the intergenic sequences. For benchmark tests, we used DNA sequence datasets extracted by ChIP-on-chip and ChIP-seq techniques and identified 65 yeast and four mammalian TFBMs, with the latter including gaps. The accuracy of our system was compared with those of other available programs (i.e. MEME, Weeder, BioProspector, MDscan and DME) and was the best among them, even without tuning of the parameter set for each TFBM and pre-treatment/editing of the target DNA sequences. Moreover, with respect to some TFs for which the identified motifs are inconsistent with those in the references, our results were revealed to be correct, by comparing them with other existing experimental data. Thus, our identification system does not need any other biological information except for gene positions, and is also expected to be applicable to genome DNA sequences to identify unknown TFBMs as well as known ones.

Effects of atelocollagen on neural stem cell function and its migrating capacity into brain in psychiatric disease model.

Stem cell therapy is well proposed as a potential method for the improvement of neurodegenerative damage in the brain. Among several different procedures to reach the cells into the injured lesion, the intravenous (IV) injection has benefit as a minimally invasive approach. However, for the brain disease, prompt development of the effective treatment way of cellular biodistribution of stem cells into the brain after IV injection is needed. Atelocollagen has been used as an adjunctive material in a gene, drug and cell delivery system because of its extremely low antigenicity and bioabsorbability to protect these transplants from intrabody environment. However, there is little work about the direct effect of atelocollagen on stem cells, we examined the functional change of survival, proliferation, migration and differentiation of cultured neural stem cells (NSCs) induced by atelocollagen in vitro. By 72-h treatment 0.01-0.05% atelocollagen showed no significant effects on survival, proliferation and migration of NSCs, while 0.03-0.05% atelocollagen induced significant reduction of neuronal differentiation and increase of astrocytic differentiation. Furthermore, IV treated NSCs complexed with atelocollagen (0.02%) could effectively migrate into the brain rather than NSC treated alone using chronic alcohol binge model rat. These experiments suggested that high dose of atelocollagen exerts direct influence on NSC function but under 0.03% of atelocollagen induces beneficial effect on regenerative approach of IV administration of NSCs for CNS disease.

Undergraduate medical students' attitudes towards psychiatry: an international cross-sectional survey between India and Japan.

Undergraduate psychiatric education has an important role in developing psychiatric knowledge, decreasing stigma towards mental illness, and promoting psychiatry as a career choice. The attitudes and beliefs of medical students towards psychiatry have not been well understood, especially in non-western countries. To clarify this aspect, we have conducted a cross-sectional study between India and Japan. This study, conducted at two centres, one each in India and Japan, used a semi-structured questionnaire to evaluate the attitudes and beliefs of third-year medical students towards mental illness and psychiatry; such as emotions experienced dealing with psychiatric patients, aetiology and treatment of psychiatric disorders, and psychiatry as a career choice. A total of 79 medical students from India and 77 from Japan participated in the present study. Significant differences were observed in the emotions experienced by the medical students while dealing with psychiatric patients. Most medical students (> 90%) from both study sites favoured psychiatrists for treatment of psychiatric illness. Psychiatry as a carrier choice was significantly related to the nationality of the medical students. The findings of the current study provide insight in to the attitudes of third-year medical students from India and Japan towards psychiatric patients.