Search

Hikikomori, a severe form of social withdrawal, is a condition characterized by the avoidance of social participation and staying at home for more than 6 months. Hikikomori was initially reported in Japan in the 1990s and is now observed worldwide. Here, we introduce specialized psychodynamic group psychotherapy for persons with hikikomori, and illustrate the case of an adult male with schizoaffective disorder. In the present report, the patient initiated an unreasonably difficult job-hunting process, became unwell, and was hospitalized. He began to participate in group psychotherapy as a place of belonging and gradually increased his social interactions. We also consider the specific difficulties exhibited by people with hikikomori, especially focusing on the avoidance around assuming responsibility for decisions and extreme dichotomous thinking. Additionally, we discuss the benefits of dealing with these difficulties in a group structure and propose the applicability of group psychotherapy in therapeutic interventions for persons with hikikomori.

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.

Background: An arteriovenous fistula (AVF) at the craniocervical junction (CCJ) is a rare vascular malformation. Definitive diagnosis and curative treatment of CCJ AVF are challenging. Case Description: A 77-year-old man presented with subarachnoid hemorrhage. Cerebral angiography showed an AVF at the CCJ, which drained into a radicular vein. The lesion was fed by a vertebral artery, anterior and lateral spinal arteries (LSAs), and the occipital artery (OA). There were two unique structures: the LSA originating from the posterior inferior cerebellar artery of the extracranial V3 segment and the OA feeding the shunt. Curative treatment involved two steps: endovascular embolization of feeders using Onyx and surgical shunt disconnection. Feeding arteries were blackened by Onyx, which helped identify the location of the shunt. The shunt was located behind the first cervical (C1) spinal nerve, and the draining vein was confirmed on the deep side of the nerve. A clip was applied to the draining vein distal to the shunt. Tiny vessels supplying the shunt were then coagulated referring to blackened arteries. Conclusion: A radicular AVF at the CCJ along the C1 spinal nerve had unique vascular structures. Definitive diagnosis and curative treatment were achieved by combining endovascular embolization using Onyx and direct surgery.

Interpersonal difficulties are often observed in major depressive disorder (MDD), while the underlying psychological and biological mechanisms have not yet been elucidated. In the present case–control study, a PC-based trust game was conducted for 38 drug-free MDD patients and 38 healthy controls (HC). In the trust game, participants invested money in a partner (trusting behaviors), and also rated each partner’s attractiveness (preference for others). In addition, blood biomarkers including metabolites were measured. Both MDD and HC males exhibited more trusting behaviors compared to females. MDD males’ preference for ordinary-attractive partners (lay-person photographs) was lower than HC males, whereas their preference for high-attractive females (fashion-model photographs) was similar levels to HC males. This tendency in MDD males could reflect a “focused (narrowed) preference for females”. As for blood biomarker analysis, the levels of 37 metabolites including acetylcholine, AMP, GMP, nicotinic acid and tryptophan were significantly different between two groups. Interestingly, among male participants, acetylcholine and nicotinic acid were negatively correlated with the level of focused preference for photographed females. In sum, we have revealed some behavioral, psychological and biological traits of trusting behaviors and preference for others especially in MDD males. Larger studies should be conducted to validate our preliminary findings.

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.

Background Oxidative stress is one of the important mechanisms underlying the pathogenesis of chronic obstructive pulmonary disease (COPD). Irisin is a type of myokine secreted from the muscle during exercise and acts against oxidative stress via nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor with antioxidant properties. Here, we examined the emphysema suppressive effects of the exercise-irisin-Nrf2 axis in mice. Methods Mice were divided into three groups, namely, the control, smoking, and exercise + smoking groups. All mice from the smoking and exercise + smoking groups were exposed to cigarette smoke once a day. The mice from the exercise + smoking group were adapted to a treadmill once a day. To investigate the Nrf2 cascade, after 12 weeks, serum irisin concentration and Nrf2 and heme oxygenase-1 (HO-1) expression in the lung homogenate were determined. To evaluate cigarette smoke-induced COPD, the number of inflammatory cells in bronchoalveolar lavage fluid (BALF), mean linear intercept (MLI), and destructive index in the lung tissue were examined. Results Serum irisin concentration and the expression levels of Nrf2 and HO-1 in the lung homogenate were significantly higher in mice from the exercise + smoking group than in those from the control and smoking groups. The proportion of neutrophils in the BALF was significantly lower in the exercise + smoking group than in the smoking group. The MLI and destructive index were also significantly smaller in mice from the exercise + smoking group than mice from the smoking group. Conclusion Irisin secreted from the muscle during exercise may exert protective effects against oxidative stress via Nrf2 and HO-1, and ameliorate emphysema of cigarette smoke-induced COPD. The exercise-irisin-Nrf2 axis may serve as a novel target for COPD treatment.

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.

研究グループは、病後や術後の食欲不振に処方される漢方薬「人参養栄湯」がCOPD(慢性閉塞性肺疾患)の骨格筋合併症に効果があることを明らかにしました。加齢や疾患により筋力が衰え、疲れやすくなり家に閉じこもりがちになるなど、健常から要介護へ移行する中間の段階である衰え全般を「フレイル」と呼び、健康寿命増進のための課題として注目されています。COPDは主にタバコ煙を吸入することにより肺胞が破壊されたり気管支が傷害されたりして生じる肺疾患であり、咳や痰、息切れの他にしばしばフレイルの中核である筋萎縮や筋力低下といった「サルコペニア(筋肉減少症)」を合併します。フレイル・サルコペニアはCOPDの予後を悪化させる因子として知られており、COPDによる死亡者数増加の一端を担っていると考えられます。そのため、COPDの骨格筋合併症に対する治療は喫緊の課題ですが、運動療法以外に単独の効果が確立されたものがないのが現状です。本研究では、人参養栄湯投与により骨格筋組織においてPGC-1α発現が亢進し、COPDモデルマウスの骨格筋合併症が改善されることが示されました。COPD患者においても人参養栄湯を摂取することでサルコペニア・フレイルの悪循環を断ち切ることができる可能性が示され、今まで克服が困難であったCOPDの骨格筋合併症の新たな治療戦略として注目されます。, Purpose: Sarcopenia, the loss of skeletal muscle mass and strength, is a common systemic consequence of chronic obstructive pulmonary disease (COPD) and is correlated with higher mortality. Ninjin’yoeito (NYT) is a Japanese herbal medicine used to treat athrepsia and anorexia and is reported to ameliorate weight loss and muscular dysfunction. Recent studies have shown that its crude components upregulate the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)-related pathway, which is involved in skeletal muscle functions. Here, we examined whether NYT improves skeletal muscle complications by upregulating PGC-1α in COPD model mice. / Materials and Methods: Mice were divided into four groups: control, NYT, smoking, and smoking + NYT. The smoking and smoking + NYT groups were exposed to cigarette smoke for 60 min once daily....

Background Social withdrawal is a feature of a number of psychiatric disorders including major depressive disorder (MDD), yet research examining social withdrawal as a feature of MDD is rare. Methods This was a retrospective case-control study. Participants (N = 67) were recruited through an outpatient clinic at an academic medical center in Japan. Major depressive disorder (MDD) and social withdrawal were established with the Structured Clinical Interview for DSM-IV Axis I Disorders and a semi-structured psychiatric interview, respectively. Participants also completed self-report measures. Results We classified 24 participants as cases (MDD with social withdrawal) and 43 participants as controls (MDD without social withdrawal). Cases, on average, were more likely to have lower education level, prior episodes of depression, and higher suicidal ideation at baseline than controls. In unadjusted regression models, cases had significantly less social connection, less reward dependence, less self-directedness, and higher scores on scales of modern-type depression and hikikomori. In adjusted regression models, associations between social withdrawal and hikikomori (p Limitations The sample was limited in size and drawn from a single site. Conclusions In patients with MDD, social withdrawal may have subtle associations with clinical symptoms, social connection, and personality traits. Developing a better understanding of social withdrawal's phenotype in depression requires more in-depth examination.

Aim Hikikomori, a form of severe social withdrawal, is an emerging issue in mental health, for which validated measurement tools are lacking. The object was to develop a self-report scale of hikikomori, and assess its psychometric properties and diagnostic accuracy. Methods A sample of 399 participants from clinical and community settings completed measures. Psychometric properties were assessed with factor analysis; diagnostic accuracy was compared against a semi-structured diagnostic interview. Results The Hikikomori Questionnaire contained 25 items across three subscales representing socialization, isolation, and emotional support. Internal consistency, test-retest reliability, and convergent validity were all satisfactory. The area under the curve was 0.86 (95% confidence interval, 0.80-0.92). A cut-off score of 42 (out of 100) was associated with a sensitivity of 94%, specificity of 61%, and positive predictive value of 17%. Conclusion The 25-item Hikikomori Questionnaire (HQ-25) possesses robust psychometric properties and diagnostic accuracy in an initial sample of Japanese adults. Additional research on its psychometric properties and ability to support clinical assessment of hikikomori is warranted.

Background Early intervention in depression has been critical to prevent its negative impact including suicide. Recent blood biomarker studies for major depressive disorder (MDD) have suggested that tryptophan-kynurenine and lipid related metabolites are involved in the pathophysiology of MDD. However, there have been limited studies investigating these blood biomarkers in first-episode drug-naive MDD, which are particularly important for early intervention in depression. Methods As an exploratory pilot case-control study, we examined the above blood biomarkers, and analyzed how these biomarkers are associated with clinical variables in first-episode drug-naive MDD patients, based on metabolome/lipidome analysis. Results Plasma tryptophan and kynurenine levels were significantly lower in MDD group (N = 15) compared to healthy controls (HC) group (N = 19), and plasma tryptophan was the significant biomarker to identify MDD group (area under the curve = 0.740). Lower serum high density lipoprotein-cholesterol (HDL-C) was the predictive biomarker for severity of depression in MDD group (R2 = 0.444). Interestingly, depressive symptoms were variously correlated with plasma tryptophan-kynurenine and lipid related metabolites. Moreover, plasma tryptophan-kynurenine metabolites and cholesteryl esters (CEs) were significantly correlated in MDD group, but not in HC group. Limitations This study had small sample size, and we did not use the multiple test correction. Conclusions This is the first study to suggest that not only tryptophan-kynurenine metabolites but also HDL-C and CEs are important blood biomarkers for first-episode drug-naive MDD patients. The present study sheds new light on early intervention in clinical practice in depression, and further clinical studies especially large-scale prospective studies are warranted.

Background: Chronic Obstructive Pulmonary Disease (COPD) is a pulmonary disease caused by long-term inhalation exposure of harmful substances, mainly cigarette smoke. Oxidative stress is considered as one of the important mechanisms of COPD. Irisin is a kind of myokine secreted from muscle by exercise. Recent studies have shown that irisin acts defensively against oxidative stress via Nrf2, a transcription factor responsible for antioxidant capacity. In this study, we examined emphysema suppression effect of exercise in mice. Methods: Mice were divided into three groups: control, smoking, and exercise+smoking. All mice in smoking and exercise+smoking groups were exposed to cigarette smoking for 60 minutes per session once a day. All mice in exercise+smoking group were adapted to treadmill for 30 minutes per session once a day. After 12 weeks intervention, serum irisin concentration, expression of Nrf2 mRNA and protein in lung homogenate, number of inflammatory cells in bronchoalveolar lavage fluid (BALF), and Mean Liner Intercept (MLI) in lung tissue were examined. Results: Serum irisin concentration and expression of Nrf2 (mRNA and protein) in lung homogenate were significantly elevated in exercise+smoking group compared to control group and smoking group. Proportion of neutrophils in BALF was significantly lower in exercise+smoking group than that in smoking group. MLI was significantly smaller in exercise+smoking group than that in smoking group. Conclusions: Our results suggested that irisin secreted from muscle by exercise might act defensively against oxidative stress via Nrf2, and ameliorate emphysema in lung. Exercise-irisin axis might be a novel target for COPD treatment.

概要：抗酸化物質で大豆などに含まれるイソフラボンがCOPD(慢性閉塞性肺疾患)の予防効果を有することを明らかにしました。COPDは日本では約500万人以上が罹患しており、進行すると咳や痰、息切れを自覚し、在宅酸素療法を必要とする患者さんもいます。COPDによる死亡者数は年々増加しており、WHO(世界保健機関)の報告ではCOPDは世界の死因第3位の疾患で、COPD患者の肺では、マクロファージや好中球などの炎症細胞の増加、肺胞壁の破壊による肺気腫が見られます。現時点では破壊された肺を元に戻す有効な治療法はなく、予防が肝要とされています。これまで疫学研究では大豆摂取によるCOPD発症リスク低減が報告されていましたが、そのメカニズムは解明されていませんでした。そこで、喫煙曝露によりCOPDを発症するマウスにイソフラボンを投与したところ、炎症細胞の減少や肺気腫の抑制効果を認めました。また、肺組織中の炎症形成に関わるサイトカイン等の上昇を抑制することも確認しました。本研究は、イソフラボンが抗炎症作用によりCOPD予防を果たすことを実験的に明らかにしたもので、今後のCOPD治療確立に向けて重要な知見であるといえます。, Chronic obstructive pulmonary disease (COPD), a lung disease caused by chronic exposure to cigarette smoke, increases the number of inflammatory cells such as macrophages and neutrophils and emphysema. Isoflavone is a polyphenolic compound that exists in soybeans. Daidzein and genistein, two types of isoflavones, have been reported to have anti-inflammatory effects in various organs. We hypothesized that the daidzein-rich soy isoflavone aglycones (DRIAs) attenuate cigarette smoke-induced emphysema in mice. Mice were divided into four groups: the (i) control group, (ii) isoflavone group, (iii) smoking group, and (iv) isoflavone + smoking group. The number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and the airspace enlargement using the mean linear intercept (MLI) were determined 12 weeks after smoking exposure. Expressions of neutrophilic inflammatory cytokines and chemokines were also examined. In the isoflavone + smoking group, the number of neutrophils in BALF and MLI was significantly less than that in the smoking group. Furthermore, the gene-expressions of TNF-α and CXCL2 (MIP-2) in the isoflavone + smoking group were significantly less than those in the smoking group. Supplementation of the COPD murine model with DRIAs significantly attenuates pathological changes of COPD via suppression of neutrophilic inflammation.

Several studies have reported that single nucleotide polymorphisms (SNPs) in the gene encoding NF-E2-related factor 2 (Nrf2) contribute to airflow limitations in smokers without COPD. Although small airway lesions and emphysema contribute cooperatively to airflow limitation, the relationship between Nrf2 SNPs and the development of emphysema in smokers without COPD is not well understood. Healthy subjects who underwent an annual health checkup with computed tomography (CT) of the chest at Osaka City University Hospital were prospectively recruited. The percentage of low-attenuation area (%LAA) on chest CT was quantified, and correlations between %LAA, Nrf2 SNP [rs6726395 (G/A)] genotypes, and clinical characteristics were examined. A total of 245 subjects without COPD [non-/light-smoker: 153 (62.4%) and smoker: 92 (37.6%)] were enrolled. The %LAA in the upper lung field was higher than that in the lower lung field (p

Although appropriate nutrition management could improve rehabilitation outcomes, more than 40 % of patients in a convalescent rehabilitation ward (CRW) suffer from malnutrition. The study was undertaken to investigate whether adequate nutrition for each patient in a CRW could be estimated based on motor scores on the Functional Independence Measure (FIM-M).In 218 patients in our CRW, both basal energy expenditure (BEE) on admission and average energy intake (EI) for 2 weeks were calculated, and EI was divided by BEE to estimate the activity index (e-AI). The patients were classified according to FIM-M to investigate the relationship between the FIM-M and the e-AI.The e-AI tended to increase in proportion to the FIM-M. In the N group, where the increase-decrease rate for body weight was within 2%, the e-AI induced by a FIM-M greater than 60 was significantly higher than that induced by a FIM-M up to 60 (1.3 vs 1.1, p0.01). Compared to the N group, altering the e-AI caused the same tendency of body weight change in patients with FIM-M greater than 60 and up to 60.The FIM-M could provide a criterial activity index for patients in a CRW when their energy requirement is appropriately estimated, considering the intensity of their physical activity.

Oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) is a key cellular defense mechanism against oxidative stress. Recent studies have shown that astaxanthin protects against oxidative stress via Nrf2. In this study, we investigated the emphysema suppression effect of astaxanthin via Nrf2 in mice. Mice were divided into four groups: control, smoking, astaxanthin, and astaxanthin + smoking. The mice in the smoking and astaxanthin + smoking groups were exposed to cigarette smoke for 12 weeks, and the mice in the astaxanthin and astaxanthin + smoking groups were fed a diet containing astaxanthin. Significantly increased expression levels of Nrf2 and its target gene, heme oxygenase-1 (HO-1), were found in the lung homogenates of astaxanthin-fed mice. The number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) was significantly decreased, and emphysema was significantly suppressed. In conclusion, astaxanthin protects against oxidative stress via Nrf2 and ameliorates cigarette smoke-induced emphysema. Therapy with astaxanthin directed toward activating the Nrf2 pathway has the potential to be a novel preventive and therapeutic strategy for COPD.

Background Neuroinflammation is suggested to be a crucial factor in the pathophysiology of major depressive disorder (MDD). Analysis of neuron-derived exosomes (NDE) in peripheral blood has recently been highlighted to reveal the pathophysiology of brain diseases without using brain biopsy. Currently, human NDE studies require a considerable amount of peripheral blood to measure multiple substances inside exosomes. Previously, NDE-based clinical studies focusing on MDD have not been reported. Methods As an exploratory pilot case-control study between healthy controls (HC) and drug-free MDD patients (each; N = 34), we searched for NDE-related blood biomarkers with a small amount of peripheral blood using a novel sandwich immunoassay between anti-neuron antibody and antibodies against CD81 (an exosome marker) and against other proteins related to neuroinflammation and synaptic functions. Results Most neuron-related blood biomarkers had moderately to strongly positive correlation with CD81 (NDE), thus we normalized the above biomarkers by CD81 (quantity of each biomarker/CD81) to predict NDE-related blood substances. Interleukin 34 (IL34)/CD81 levels were significantly higher in MDD group compared to HC group. Synaptophysin (SYP), SYP/CD81, and tumor necrosis factor receptor 1 (TNFR1)/CD81 were positively correlated with severities of depression and/or various sub-symptoms. Limitations We did not actually extract NDE from peripheral blood. Conclusions Using a small amount of peripheral blood, we have successfully detected possible NDE-related blood biomarkers. This is the first study to suggest that not only SYP and TNFR1 but also IL34 are important blood biomarkers for patients with MDD. Further studies are warranted to evaluate the present study.

ObjectiveIn the workplace depression and suicide are serious mental health problems. A lack of knowledge and mental health skills along with the stigma toward mental health problems often results in delays in seeking professional help. Interventions targeting not only persons with mental health problems but also people around the individual are warranted in order to encourage supporting behavior within entire workplace. In the present study, we investigated the efficacy of our newly developed educational training program in the management with depression and suicidal risk in the workplace as a single-arm pilot trial.MethodsThe program is a two-hour (2-h) training course for employees based on the Mental Health First Aid (MHFA) program which aims to increase public mental health literacy. We conducted this program at a company workplace among 91 employees, and ultimately 83 participants completed the self-rated questionnaires. Changes in confidence and practical skills in early intervention of depression and suicide-prevention, and stigma toward mental health problems were evaluated using self-rated questionnaires at 3 time-points; pre-program, immediately post-program, and 1 month after the program.ResultsConfidence and practical skills were significantly improved even 1 month after the program, and stigma reduced just after the program.ConclusionsOur pilot study suggests that the program has a positive impact on encouraging employees to support their co-workers with mental health problems, and is applicable for busy workers due to its short duration. A single-arm design, evaluation using self-rated questionnaire and short-term follow up period are the main limitations of the present study. Hence, future research is required to validate the effects of this program with control groups, and also to assess long-term effectiveness and objective changes such as absenteeism and sick leave.Trial registrationUMIN Clinical Trials Registry (UMIN-CTR) R000023258.

Japan's prototype of depression was traditionally a melancholic depression based on the premorbid personality known as shūchaku-kishitsu proposed by Mitsuzo Shimoda in the 1930s. However, since around 2000, a novel form of depression has emerged among Japanese youth. Called 'modern type depression (MTD)' by the mass media, the term has quickly gained popularity among the general public, though it has not been regarded as an official medical term. Likewise, lack of consensus guidelines for its diagnosis and treatment, and a dearth of scientific literature on MTD has led to confusion when dealing with it in clinical practice in Japan. In this review article, we summarize and discuss the present situation and issues regarding MTD by focusing on historical, diagnostic, psychosocial, and cultural perspectives. We also draw on international perspectives that begin to suggest that MTD is a phenomenon that may exist not only in Japan but also in many other countries with different sociocultural and historical backgrounds. It is therefore of interest to establish whether MTD is a culture-specific phenomenon in Japan or a syndrome that can be classified using international diagnostic criteria as contained in the ICD or the DSM. We propose a novel diagnostic approach for depression that addresses MTD in order to combat the current confusion about depression under the present diagnostic systems.

Pancreatic neuroendocrine tumors (pNETs) are histologically categorized according to the WHO 2010 classification by their mitotic index or Ki-67 index as G1, G2, or G3. The present study examined the efficacy of endoscopic ultrasonography (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) in the diagnosis and grading of pNET.We retrospectively reviewed 61 pNETs in 51 patients who underwent EUS between January 2007 and June 2014. All lesions were pathologically diagnosed by surgical resection or EUS-FNA. We evaluated the detection rates of EUS for pNET and sensitivity of EUS-FNA, and compared the Ki-67 index between EUS-FNA samples and surgical specimens. EUS findings were compared between G1 and G2/G3 tumors.EUS showed significantly higher sensitivity (96.7%) for identifying pNET than CT (85.2%), MRI (70.2%), and ultrasonography (75.5%). The sensitivity of EUS-FNA for the diagnosis of pNET was 89.2%. The concordance rate of WHO classification between EUS-FNA and surgical specimens was 69.2% (9/13). The concordance rate was relatively high (87.5%, 5/6) in tumors 20 mm but lower (57.1%; 4/7) in tumors ≥20 mm. Regarding EUS findings, G2/G3 tumors were more likely to be large (20 mm), heterogeneous, and have main pancreatic duct (MPD) obstruction than G1 tumors. Multivariate analysis showed large diameter and MPD obstruction were significantly associated with G2/G3 tumors.EUS and EUS-FNA are highly sensitive and accurate diagnostic methods for pNET. Characteristic EUS findings such as large tumor size and MPD obstruction are suggestive of G2/G3 tumors and would be helpful for grading pNETs.

Background: Pulmonary fibrosis is a life-threatening disease characterized by progressive dyspnea and worsening of pulmonary function. Ghrelin is a growth hormone-releasing peptide originally isolated from the rat stomach in 1999. The actions of ghrelin include appetite stimulation, carbohydrate utilization, and growth hormone release. Recent studies have shown that ghrelin has various anti-inflammatory effects in various experimental models. Aims and objective: We hypothesized that ghrelin had anti-inflammatory and anti-fibrotic effects on bleomycin (BLM)-induced pulmonary fibrosis in mice. Methods: Mice were divided into three groups: normal control, BLM with vehicle, and BLM with ghrelin. Ghrelin (0.8 μg/kg/min via osmotic-pump, subcutaneously) or vehicle administration was started two days before BLM administration (1 mg/kg) and continued until the mice were sacrificed. At 7 and 21 days after BLM administration, infiltration of inflammatory cells and fibrotic changes in the lungs were assessed based on analysis of bronchoalveolar lavage fluid and histological examinations including Masson trichrome-staining. In addition, fibrosis and inflammation induced by BLM were evaluated in global ghrelin knockout mice. Results: Ghrelin significantly attenuated total and macrophage cell counts at 7 days and attenuated fibrotic areas at 21 days in murine lungs after BLM administration. Furthermore, total and macrophage cell counts were increased in ghrelin knockout mice. Conclutions: Ghrelin exerts protective effects on BLM-induced pulmonary inflammation and fibrosis. Endogenous ghrelin may play an important role in the pathophysiological process in pulmonary fibrosis.

Background Suicide is a crucial global health concern and effective suicide prevention has long been warranted. Mental illness, especially depression is the highest risk factor of suicide. Suicidal risk is increased in people not only with mental illness but also with physical illnesses, thus medical staff caring for physically-ill patients are also required to manage people with suicidal risk. In the present study, we evaluated our newly developed suicide intervention program among medical staff. Methods We developed a 2-h suicide intervention program for medical staff, based on the Mental Health First Aid (MHFA), which had originally been developed for the general population. We conducted this program for 74 medical staff members from 2 hospitals. Changes in knowledge, perceived skills, and confidence in early intervention of depression and suicide-prevention were evaluated using self-reported questionnaires at 3 points; pre-program, immediately after the program, and 1 month after program. Results This suicide prevention program had significant effects on improving perceived skills and confidence especially among nurses and medical residents. These significant effects lasted even 1 month after the program. Limitations Design was a single-arm study with relatively small sample size and short-term follow up. Conclusions The present study suggests that the major target of this effective program is nurses and medical residents. Future research is required to validate the effects of the program with control groups, and also to assess long-term effectiveness and actual reduction in suicide rates.

Idebenone is a benzoquinone analog that is used in the treatment of several neurological disorders including Friedreich's ataxia. It was found that the reaction of idebenone with 2-cyanoacetamide under alkaline conditions generates fluorescent products, and the reaction was considered to proceed via Craven's reaction. The reaction mixture from idebenone gave fluorescence with excitation and emission maximum wavelengths at 358 nm and 409 nm, respectively. It was adopted for HPLC with post-column fluorescence derivatization of idebenone. Idebenone in the plasma showed a linear response in the range of 0.5-32 ng (25-1600 ng/mL), and the quantitation limit (S/N=10) was 12.5 ng/mL. The detection limit (S/N=3) of the standard solution of idebenone was 0.1 ng. The HPLC system was applied to the human blood plasma obtained by finger prick. The plasma sample obtained by finger prick gave a similar chromatogram to that of venous blood obtained by venipuncture.

Although the World Health Organisation (WHO) defined a novel classification of gastroenteropancreatic neuroendocrine tumours (NETs) in 2010, indications for endoscopic resection of rectal NETs in the guidelines were based on evidence accumulated for carcinoid tumours defined by a previous classification. This study was designed to clarify indications for endoscopic resection of rectal NETs corresponding to the new WHO classifications.One hundred-seventy rectal NETs resected endoscopically from April 2001 to March 2012 were histologically re-classified according to the WHO 2010 criteria. The clinicopathological features of these lesions were analysed, and the short- and long-term outcomes of endoscopic resection were evaluated.Of the 170 rectal NETs, 166 were histopathologically diagnosed as NET G1 and four as NET G2. Thirty-eight tumours (22.4%) were positive for lymphovascular invasion, a percentage higher than expected. Although the curative resection rate was low (65.3%), en bloc (98.8%) and complete (85.9%) resection rates were high. Modified endoscopic mucosal resection (88.0%) and endoscopic submucosal dissection (92.2%) resulted in significantly higher complete resection rates than conventional endoscopic mucosal resection (36.4%). No patient experienced tumour recurrence, despite the low curative resection rate.Despite the low curative resection rate, prognosis after endoscopic resection of rectal NETs was excellent. Prospective large-scale, long-term studies are required to determine whether NET G2 and tumours1 cm should be included in the indication for endoscopic resection and whether tumours with lymphovascular invasion can be followed up without additional surgery.

It was shown that ubiquinone (CoQ(10)) and ubiquinol (CoQ(10)H(2)) produce fluorescence products under alkaline conditions when reacted with 2-cyanoacetamide. The reaction mixture from CoQ(10) gave fluorescence with excitation and emission maximum wavelengths at 442 nm and 549 nm, respectively. This reaction was considered to proceed via Craven's reaction. Moreover, 2-cyanoacetamide was shown to be a useful reagent for high-performance liquid chromatography (HPLC) with post-column fluorescence derivatization of CoQ(10) and CoQ(10)H(2) in blood. CoQ(10) showed a linear response in the range of 0.32-1276 ng, and the detection limit (S/N = 3) was 0.16 ng. Moreover, the sample pretreatment by deproteinization and extraction of CoQ(10) and CoQ(10)H(2) from plasma using 1-propanol with potassium formate was effective for excellent separation of CoQ(10) and CoQ(10)H(2) from other fluorescent substances in the blood. This simple and rapid pretreatment was considered to minimize the oxidation of CoQ(10)H(2). On the other hand, CoQ(10) and CoQ(10)H(2) in plasma samples obtained by finger prick were detected, as in venous blood obtained by venipuncture. Our method involving the simple and rapid collection of plasma by finger prick and sample pretreatment is thought to be applicable for the determination of CoQ(10)H(2)/total CoQ(10) ratio as a biomarker of oxidative stress.

GIS (Geographic Information System) is an effective tool also to visualize regional environment information in bird's-eye view. In this paper, some examples of the examination of the visualization technique to make our WEB site, "Osaka University Yodogawa Basin Project", more rational as an environment-information offer site. They are, (1) Display of the historical change as a diagnostic technique, (2) Selection standard of colors used for visualization, and (3) Display of the multi-dimension information by superposition of colors. Although the example which utilizes WEB-GIS for offer of environment information is predicted to increase from now on, the argument about the function required of environmental GIS has just started. From now on, the further examination will be required.

A high selectivity analytical method for p‐hydroxymethamphetamine (pOHMA) in urine is presented. After extraction, the analyte was analyzed by high performance liquid chromatography with post‐column oxidation using potassium hexacyanoferrate(III) and sodium hydroxide to detect the fluorophor of pOHMA. The recovery of pOHMA is 86.5%, and the calibration curve for pOHMA is linear in the range of 5–75 µg/mL (r 2=0.997). The coefficients of variation determined for spiked samples are 2.2% for 10 µg/mL and 2.3% for 5 µg/mL pOHMA (each n=5), and the detection limit for pOHMA is 1 µg/mL (20 ng; S/N=3). Analysis for pOHMA in forensic samples is performed successfully, without interference from endogenous fluorophors, yielding concentrations in the appropriate range for methamphetamine abusers.

We report a case of steroid-induced osteonecrosis in a patient with refractory ulcerative colitis. A 31 year-old woman presented suffering from refractory ulcerative colitis. She had been treated by prednisolone for ten years. Sharp pain and swelling appeared suddenly in her right knee. Conventional radiography revealed neither osteoporosis nor a fracture. However, magnetic resonance imaging by T1-, T2- and T2*-weighted images revealed irregular heterogeneous areas of low- and high-intensity in her right femur and tibia. For a precise early diagnosis of osteonecrosis, bone magnetic resonance imaging was found to be an excellent diagnostic tool., 難治性潰瘍性大腸炎に合併したステロイド性骨壊死症の一例を報告した.患者は,31歳女性.難治性潰瘍性大腸炎に対して10年前よりプレドニゾロン投与を受けており精査加療目的にて当科入院となった.入院加療中,突然,右膝の痺痛・腫脹が出現.単純X線写真では,同部に骨粗籟症も骨折像も指摘できなかったが,核磁気共鳴画像(MRI)T1,T2・強調像にて右大腿骨・脛骨に低,高信号が混在する不均一な不整形領域を認めステロイド性骨壊死と診断し得た.ステロイド性骨壊死の正確な早期診断には,MRIが極めて有用である.