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Background: Self-harm is an important risk factor for subsequent suicide and repetition of self-harm, and a common cause of emergency department presentations. However, there still remains limited evidence on intervention in emergency department settings for individuals who self-harm.Methods: This multicentre, randomised controlled trial was conducted at 17 general hospitals in Japan. In total, 914 adult patients admitted to emergency departments for a suicide attempt and had a DSM-IV-TR axis I disorder were randomly assigned to two groups, to receive either assertive case management (intervention) or enhanced usual care (control). Assertive case management was introduced by the case manager during emergency department admissions for suicide attempts, and continued after discharge. Interventions were provided until the end of the study period (for at least 18 months and up to 5 years).Results: The number of overall self-harm episodes per person-year was significantly lower in the intervention group (adjusted incidence risk ratio (IRR) 0.88, 95%CI 0.80-0.96, p=0.0031). Subgroup analysis showed a greater reduction of overall self-harm episodes among patients with no previous suicide attempt at baseline (adjusted IRR 0.73, 95% CI 0.53-0.98, p=0.037).Limitations: Patients younger than 20 years and patients who self-harmed but were not admitted to an emergency department were excluded.Conclusions: The present study showed that assertive case management following emergency admission for a suicide attempt reduced the incident rate of repeat overall self-harm. [ABSTRACT FROM AUTHOR]

Abstract: Suicidality in patients with schizophrenia is high. To clarify the characteristics of suicidal behavior in patients with schizophrenia, we investigated suicide attempters with schizophrenia spectrum disorders in comparison with patients with mood disorders. One hundred patients with schizophrenia spectrum disorders and 155 patients with mood disorders admitted to an emergency department after a suicide attempt were interviewed in detail on items concerning 1) demographic characteristics, 2) previous suicidal behavior, and 3) index suicidal behavior. Differences between the two groups were subsequently analyzed. Patients with schizophrenia spectrum disorders showed a lower incidence of previous deliberate self-harm, and a higher incidence of a subsequent suicide attempt more than 1 year after the previous suicide attempt as well as a higher lethality of index suicide attempt compared to patients with mood disorders. Furthermore, the most common motive for making a suicide attempt in patients with schizophrenia spectrum disorders was having a mental problem. This study revealed the factors associated with suicide attempts among Japanese patients with schizophrenia spectrum disorders, and the nature of these factors makes it difficult to predict future attempts. This makes clear the importance of continuous long-term follow-up with careful attention to the mental symptoms and psychological burden for such patients. [Copyright &y& Elsevier]

• We report the unexpected novel finding that exogenously supplied atmospheric NO2 at an ambient concentration is a plant vitalization signal to double shoot size and the contents of cell constituents. • When seedlings of Nicotiana plumbaginifolia were grown for 10 wk under natural light and irrigation with 10 m m KNO3 in air containing (+NO2 plants) or not containing (–NO2 plants) 15NO2 (150 ± 50 ppb), shoot biomass, total leaf area, and contents per shoot of carbon (C), nitrogen (N), sulphur (S), phosphorus (P), potassium (K), calcium (Ca), magnesium (Mg), free amino acids and crude proteins were all approximately 2 times greater in +NO2 plants than in –NO2 plants. • In mass spectrometric analysis of the 15N/14N ratio, it was found that NO2-derived N (NO2-N) comprised < 3% of total plant N, indicating that the contribution of NO2-N to total N was very minor. • It thus seems very likely that the primary role of NO2 is as a multifunctional signal to stimulate plant growth, nutrient uptake and metabolism. [ABSTRACT FROM AUTHOR]

A response by Makiko Nakagawa and Chiaki Kawanishi to a letter to the editor about his article on suicide attempters who were given crisis intervention during hospital stay: published in the previous issue is presented.

A letter to the editor is presented about a study of suicide attempters who were given crisis intervention during hospital stay.

The kinase mTOR (mammalian target of rapamycin) promotes translation as well as cell survival and proliferation under nutrient-rich conditions. Whereas mTOR activates translation through ribosomal protein S6 kinase (S6K) and eukaryotic translation initiation factor 4E-binding protein (4E-BP), how it facilitates cell proliferation has remained unclear. We have now identified p19Arf, an inhibitor of cell cycle progression, as a novel substrate of S6K that is targeted to promote cell proliferation. Serum stimulation induced activation of the mTOR-S6K axis and consequent phosphorylation of p19Arf at Ser75. Phosphorylated p19Arf was then recognized by the F-box protein β-TrCP2 and degraded by the proteasome. Ablation of β-TrCP2 thus led to the arrest of cell proliferation as a result of the stabilization and accumulation of p19Arf. The β-TrCP2 paralog β-TrCP1 had no effect on p19Arf stability, suggesting that phosphorylated p19Arf is a specific substrate of β-TrCP2. Mice deficient in β-TrCP2 manifested accumulation of p19Arf in the yolk sac and died in utero. Our results suggest that the mTOR pathway promotes cell proliferation via β-TrCP2-dependent p19Arf degradation under nutrient-rich conditions. [ABSTRACT FROM AUTHOR]

Summary DNA methylation at the C-5 position of cytosine (5mC) regulates gene expression and plays pivotal roles in various biological processes. The TET dioxygenases catalyze iterative oxidation of 5mC, leading to eventual demethylation. Inactivation of TET enzymes causes multistage developmental defects, impaired cell reprogramming, and hematopoietic malignancies. However, little is known about how TET activity is regulated. Here we show that all three TET proteins bind to VprBP and are monoubiquitylated by the VprBP-DDB1-CUL4-ROC1 E3 ubiquitin ligase (CRL4 VprBP ) on a highly conserved lysine residue. Deletion of VprBP in oocytes abrogated paternal DNA hydroxymethylation in zygotes. VprBP-mediated monoubiquitylation promotes TET binding to chromatin. Multiple recurrent TET2-inactivating mutations derived from leukemia target either the monoubiquitylation site (K1299) or residues essential for VprBP binding. Cumulatively, our data demonstrate that CRL4 VprBP is a critical regulator of TET dioxygenases during development and in tumor suppression. [ABSTRACT FROM AUTHOR]

Aim: The Social Adaptation Self-evaluation Scale (SASS) was developed to assess the social impairment caused by depression. The purposes of this study were to develop a Japanese version of the SASS (SASS-J) and to evaluate its reliability and validity. Methods: The SASS-J and the 21-item Beck Depression Inventory (BDI) were administered to 322 participants (95 working patients who were working while under treatment for depression, 99 non-working patients who were absent from their work due to depression, and 128 healthy controls). The healthy controls underwent both questionnaires twice, at baseline and 2 weeks later, in order to assess test-retest reliability. Results: Cronbach's alpha was 0.81. Significance correlations were found between SASS-J scores at baseline and 2 weeks later in healthy controls (R = 0.845, P < 0.001). There were negative correlations between the SASS-J and BDI scores (ρ = -0.683, P < 0.001). Mean SASS-J scores differed significantly among the three groups (working patients: 33.7 ± 7.9; non-working patients: 25.2 ± 7.8; healthy controls: 36.1 ± 6.0 [mean ± SD]). The best compromise between the true positive and the false negative rate in this study was at a cut-off point of 25/26. Conclusion: SASS-J showed sufficient reliability and validity, and could be considered a suitable instrument to evaluate social functioning in depressive patients. [ABSTRACT FROM AUTHOR]

Background: Extragonadal germ cell tumor (EGCT) is a relatively rare condition, reportedly representing 3-7% of all germ cell tumors. We report a patient who had metachronous testicular tumor with uncommon metastases 20 years after primary retroperitoneal EGCT treatment, along with a corresponding literature review.Case Presentation: A 49-year-old Japanese man visited our department in November 2017 with chief complaints of indolent right scrotum enlargement and a right inguinal mass. History showed that the patient visited our department of gastroenterology with chief complaints of blackish feces and ill complexion in February 1997. Computed tomography (CT) showed a right retroperitoneal tumor, which was removed in the same month. Histopathological examination showed a teratoma and yolk sac tumor. He was diagnosed with primary retroperitoneal EGCT and received three courses of chemotherapy (bleomycin/etoposide/cisplatin; BEP). Periodic imaging and the determination of tumor markers (alpha-fetoprotein [AFP], human chorionic gonadotropin [HCG], and lactate dehydrogenase [LDH]) showed no recurrence or metastasis during the 5 years postoperatively. Subsequently, he did not visit the outpatient ward. In August 1999, he underwent surgery of right hydrocele. Contrast-enhanced CT showed a 35-mm contrast effect with uneven content in the right testicle and enlarged nodes that raised suspicion for metastases in the right inguinal and right external iliac lymph nodes. All tumor markers were within normal ranges. He underwent right high orchiectomy and resection of the right inguinal lymph nodes in the same month. Histopathological findings revealed seminoma (pT1, pN2, M0, S0, and TNM stage IIB). He received postoperative chemotherapy, one course of BEP therapy, and three courses of etoposide and cisplatin therapy. Post-chemotherapy CT confirmed a complete clinical response at the right external iliac lymph nodes, and this response continued 12 months later. No recurrence or metastasis has been found so far.Conclusions: We report a patient in whom a testicular tumor with uncommon metastases occurred 20 years after primary retroperitoneal EGCT treatment. After EGCT treatment, testicular relapses tend to occur after relatively long-term follow-up. After EGCT treatment, such patients must be closely monitored for testicular recurrences and onset of testicular tumor. [ABSTRACT FROM AUTHOR]

Suicide attempt is a risk factor for suicide. To investigate trait impulsivity among suicide attempters, 93 attempters admitted to an emergency department and 113 healthy controls were evaluated using the Japanese version of the Barratt Impulsiveness Scale (BIS-11J). Impulsivity was analyzed in relation to clinical data in the attempters. Total BIS-11J, attention impulsiveness, and motor impulsiveness scores were significantly higher in the attempters than in the controls. Both total BIS-11J and non-planning impulsiveness scores were significantly higher in attempters with schizophrenia and other psychotic disorders among the diagnostic groups. Control of impulsivity should be considered as one of the targets for suicide prevention. [ABSTRACT FROM AUTHOR]

Background: Some reports have suggested the involvement of the D2 dopaminergic function in the expression of suicidal behavior. Here, we examined associations between suicide attempts and two kinds of functional polymorphisms in the dopamine D2 receptor (DRD2) gene, namely, TaqIA and –141C Ins/Del. Methods: Subjects included 120 suicide attempters and 123 unrelated volunteers. Those who attempted suicide were severely injured and were transferred to the emergency unit in our university hospital. To determine each genotype, we performed polymerase chain reaction and restriction fragment length polymorphism analyses. Results: We found significant differences in genotypic and allelic frequencies of –141C Ins/Del and TaqIA polymorphisms between suicide attempters and healthy controls (–141C Ins/Del, p = 0.01; TaqIA,p = 0.036). The Ins allele of –141C Ins/Del was significantly more frequent in suicide attempters (p = 0.011), as well as the A2 allele of TaqIA (p = 0.017). Haplotype analysis revealed no significant linkage disequilibrium between –141C Ins/Del and TaqIA polymorphisms (D′ = 0.226, r2 = 0.016, p = 0.10). Conclusions: These findings suggest that DRD2 gene polymorphisms may be involved in the biological susceptibility to suicide. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Suicide attempt is a potent risk factor of subsequent suicide. Understanding the characteristics of suicide attempters is important for preventing suicide. The authors investigated aggression in medically serious suicide attempters at an emergency department. Trait aggression was evaluated in 55 suicide attempters and 71 healthy individuals as a control group using the Japanese version of the Buss-Perry Aggression Questionnaire (BAQ). Total BAQ scores ( t = 2.782, P = 0.006) and the hostility scores ( t = 3.735, P < 0.001) were significantly higher in the suicide attempters than the controls. It suggested that to focus on aggression and its management is one of the key components for preventing suicide. [ABSTRACT FROM AUTHOR]