Synthesis of 2-Substituted Indoles via Migration Reaction of 3-Substituted Indoles with Triflic Acid.

This study showcases the 1,2-migration reactions of alkyl and aryl groups on the indole molecule. Trifluoromethanesulfonic acid effectively facilitates the migration of the substituent from C3- to C2-position of the indole structure. The resulting C2-substituted indoles offer a valuable pathway for the synthesis of natural products and medicinal compounds.

Effect of Personality Traits on Sustained Remission Among Patients with Major Depression: A 12-Month Prospective Study.

Purpose: Major depression is a heterogeneous disorder. Therefore, careful evaluation and comprehensive assessment are crucial elements for achieving remission. Personality traits influence prognosis and treatment outcomes, but there is not enough evidence on the association between personality traits and sustained remission (SR). Hence, the present study aimed to evaluate the relationship between personality traits and SR among patients with major depression. Patients and Methods: The 12-month prospective study evaluated 77 patients diagnosed with major depressive disorder. All patients underwent a comprehensive assessment, including the Temperament and Personality Questionnaire (T&P) at baseline, and depression severity was measured at baseline as well as six and 12 months. SR was defined as remission (the GRID-Hamilton Depression Rating Scale [GRID-HAMD17] score ≦ 7) at both the 6- and 12-month follow-up. We compared eight T&P construct scores at baseline between the SR and non-SR groups. Multivariable logistic regression analyses were performed to determine the T&P personality traits related to SR. Results: Patients who achieved SR had a lower T&P personal reserve and lower T&P rejection sensitivity. Further, lower scores on the T&P personal reserve trait were independently associated with higher rates of SR among patients with major depression. Patients who achieved SR had a shorter duration of the current depressive episode and milder severity of depression at baseline. Conclusion: A lower level of personal reserve predicted a higher probability of SR in the treatment of depression. Extended observations in naturalistic follow-up settings with larger sample sizes are required to better understand the personality traits affecting SR in patients with depression.

Web-Based Cognitive Behavioral Therapy Blended With Face-to-Face Sessions for Major Depression: Randomized Controlled Trial.

BACKGROUND: Meta-analyses of several randomized controlled trials have shown that cognitive behavioral therapy (CBT) has comparable efficacy to antidepressant medication, but therapist availability and cost-effectiveness is a problem. OBJECTIVE: This study aimed to evaluate the effectiveness of Web-based CBT blended with face-to-face sessions that reduce therapist time in patients with major depression who were unresponsive to antidepressant medications. METHODS: A 12-week, assessor-masked, parallel-group, waiting- list controlled, randomized trial was conducted at 3 medical institutions in Tokyo. Outpatients aged 20-65 years with a primary diagnosis of major depression who were taking ≥1 antidepressant medications at an adequate dose for ≥6 weeks and had a 17-item GRID-Hamilton Depression Rating Scale (HAMD) score of ≥14 were randomly assigned (1:1) to blended CBT or waiting-list groups using a computer allocation system, stratified by the study site with the minimization method, to balance age and baseline GRID-HAMD score. The CBT intervention was given in a combined format, comprising a Web-based program and 12 45-minute face-to-face sessions. Thus, across 12 weeks, a participant could receive up to 540 minutes of contact with a therapist, which is approximately two-thirds of the therapist contact time provided in the conventional CBT protocol, which typically provides 16 50-minute sessions. The primary outcome was the alleviation of depressive symptoms, as measured by a change in the total GRID-HAMD score from baseline (at randomization) to posttreatment (at 12 weeks). Moreover, in an exploratory analysis, we investigated whether the expected positive effects of the intervention were sustained during follow-up, 3 months after the posttreatment assessment. Analyses were performed on an intention-to-treat basis, and the primary outcome was analyzed using a mixed-effects model for repeated measures. RESULTS: We randomized 40 participants to either blended CBT (n=20) or waiting-list (n=20) groups. All patients completed the 12-week treatment protocol and were included in the intention-to-treat analyses. Participants in the blended CBT group had significantly alleviated depressive symptoms at week 12, as shown by greater least squares mean changes in the GRID-HAMD score, than those in the waiting list group (-8.9 points vs -3.0 points; mean between-group difference=-5.95; 95% CI -9.53 to -2.37; P<.001). The follow-up effects within the blended CBT group, as measured by the GRID-HAMD score, were sustained at the 3-month follow-up (week 24) and posttreatment (week 12): posttreatment, 9.4 (SD 5.2), versus follow-up, 7.2 (SD 5.7); P=.009. CONCLUSIONS: Although our findings warrant confirmation in larger and longer term studies with active controls, these suggest that a combined form of CBT is effective in reducing depressive symptoms in patients with major depression who are unresponsive to antidepressant medications. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry: UMIN000009242; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000010852 (Archived by WebCite at http://www.webcitation. org/729VkpyYL).

Suicidal patients presenting to secondary and tertiary emergency departments and referral to a psychiatrist: a population-based descriptive study from Japan.

BACKGROUND: In Japan, although many suicidal studies were previously conducted in tertiary emergency department (ED) settings, no published studies have reported on suicidal patients presenting to the secondary EDs. The aim of the study was to describe the characteristics of suicidal patients and the referral rates to a psychiatrist overall and by type of facility. METHODS: Questionnaires were sent to all secondary and tertiary EDs in Tochigi prefecture, Japan. Data were collected for cases who presented in September 2009. Chi-square, Fisher's exact, and t-tests compared the results by gender and type of ED. RESULTS: All 74 EDs responded to the survey. There were 81 patients who attempted or died by suicide (36 men and 45 women). The most common method of suicide attempt was drug overdose (57%) followed by stabbing (17%). About a half used prescription drugs to attempt or die by suicide. The majority had a history of psychiatric disorders, and 35% had previous suicide attempt. About a half were admitted to medical or surgical unit; 33% were discharged home; and 9% died. After excluding those who died, 53% were referred to a psychiatrist, but 47% were not referred to a psychiatrist. The referral rate was lower for cases seen at secondary EDs (38%) compared to tertiary EDs (67%). CONCLUSION: Although professional organizations suggest that suicidal patients are seen by a psychiatrist, many were not, especially at secondary EDs. Further research is needed to assure that suicidal patients presenting to EDs receive appropriate psychiatric assessment and follow-up after discharge.

Retinal Circuit Emulator With Spatiotemporal Spike Outputs at Millisecond Resolution in Response to Visual Events.

To gain insights on how visual information of the real world is filtered, compressed, and encoded by the vertebrate retinas, emulating in silico the spatiotemporal patterns of the graded and action potentials of neuronal responses to natural visual scenes on biological time scale is a feasible approach. As a basic platform for such an emulation, we here developed a compact hardware system comprising an analog silicon retina and a field-programmable gate array module. With utilizing the Izhikevich formalism, a retinal circuit model that emulates spiking of ganglion cells was implemented in this system. The emulated spike timing had the resolution of about 2 ms relative to the stimulus onset and was little affected by timings of the synchronous frame sampling in the silicon retina. Thus, the emulator can mimic the event-driven spike outputs of biological retinas. The system was useful for simultaneously visualizing neural images of both the graded potentials and the spikes in response to real live visual scenes. Since our emulator system is reconfigurable, it provides a flexible platform for investigating visual functions of retinal circuits under natural visual environment.

Temperament, personality, and treatment outcome in major depression: a 6-month preliminary prospective study.

BACKGROUND: Despite available treatments, major depression is a highly heterogeneous disorder, which leads to problems in classification and treatment specificity. Previous studies have reported that personality traits predict and influence the course and treatment response of depression. The Temperament and Personality Questionnaire (T&P) assesses eight major constructs of personality traits observed in those who develop depression. The aim of this study was to investigate the influence of T&P's eight constructs on the treatment outcome of depressed patients. PATIENTS AND METHODS: A preliminary 6-month prospective study was conducted with a sample of 51 adult patients with a diagnosis of major depressive disorder (MDD) without remarkable psychomotor disturbance using the Diagnostic and Statistical Manual of Mental Disorders, fourth edition. All patients received comprehensive assessment including the T&P at baseline. We compared each T&P construct score between patients who achieved remission and those who did not achieve remission after 6 months of treatment for depression using both subjective and objective measures. All 51 (100%) patients received the 6-month follow-up assessment. RESULTS: This study demonstrated that higher scores on T&P personal reserve predicted poorer treatment outcome in patients with MDD. Higher levels of personal reserve, rejection sensitivity, and self-criticism correlated with higher levels of depression. Higher levels of rejection sensitivity and self-criticism were associated with non-remitters; however, when we controlled for baseline depression severity, this relationship did not show significance. CONCLUSION: Although the results are preliminary, this study suggests that high scores on T&P personal reserve predict poorer treatment outcome and T&P rejection sensitivity and self-criticism correlate with the severity of depression. Longer follow-up studies with large sample sizes are required to improve the understanding of these relationships.

The reliability and validity of the Japanese version of the Temperament and Personality Questionnaire for patients with non-melancholic depression.

BACKGROUND: Parker et al. (2006) proposed a new approach to classify specific sub-types of non-melancholic depression caused by various stress factors and premorbid personality styles: the Temperament and Personality Questionnaire (T&P). The current study aim was to develop the Japanese version of the T&P and evaluate its reliability and validity. METHODS: We studied 114 patients with non-melancholic depression. Reliability was assessed using the test-retest method. Convergent validity of the T&P was compared with the clinician ratings of each patient for the eight personality traits. We also assessed the impact of depressive state on the T&P. RESULTS: The test-retest intraclass correlation coefficients among eight constructs of the T&P ranged from 0.77 to 0.89, indicating good-to-excellent reliability. Anxious Worrying (rho=0.29), Perfectionism (rho=0.17), Personal Reserve (rho=0.18), Irritability (rho=0.38), and Social Avoidance (rho=0.32) showed adequate levels of convergent validity; Rejection Sensitivity (rho=0.16), Self-criticism (rho=-0.02), and Self-focus (rho=0.07) showed relatively weak convergent validity. Perfectionism (rho=-0.06), Social Avoidance (rho=0.17), Anxious Worrying (rho=0.40), Personal Reserve (rho=0.30), Irritability (rho=0.28), Rejection Sensitivity (rho=0.35), Self-criticism (rho=0.49), and Self-focus (rho=0.24) showed minimal sensitivity to mood state effects. LIMITATIONS: Only one site was used. While a Likert scale was used, the clinician-rated personality trait measure had not been validated. CONCLUSIONS: The J-T&P is a reliable and valid measure for assessing temperament and personality in Japanese patients with non-melancholic depression.

Oral health in the Japan self-defense forces - a representative survey.

BACKGROUND: The oral health of military populations is usually not very well characterized compared to civilian populations. The aim of this study was to investigate two physical oral health characteristics and one perceived oral health measure and their correlation in the Japan self-defense forces (JSDF). METHODS: Number of missing teeth, denture status, and OHRQoL as evaluated by the Japanese 14-item version of the Oral Health Impact Profile (OHIP-J14) as well as the correlation between these oral health measures was investigated in 911 personnel in the JSDF. RESULTS: Subjects did not have a substantial number of missing teeth and only 4% used removable dentures. The mean OHIP-J14 score was 4.6 ± 6.7 units. The magnitude of the correlation between the number of missing teeth with OHIP-J14 scores was small (r = 0.22, p < 0.001). Mean OHIP-J14 scores differed between subjects with and without dentures (8.6 and 4.4, p < 0.001). CONCLUSIONS: Compared to Japanese civilian populations, personnel of the JSDF demonstrated good oral health. Two physical oral health characteristics were associated with perceived oral health.

Hda monomerization by ADP binding promotes replicase clamp-mediated DnaA-ATP hydrolysis.

ATP-DnaA is the initiator of chromosomal replication in Escherichia coli, and the activity of DnaA is regulated by the regulatory inactivation of the DnaA (RIDA) system. In this system, the Hda protein promotes DnaA-ATP hydrolysis to produce inactive ADP-DnaA in a mechanism that is mediated by the DNA-loaded form of the replicase sliding clamp. In this study, we first revealed that hda translation uses an unusual initiation codon, CUG, located downstream of the annotated initiation codon. The CUG initiation codon could be used for restricting the Hda level, as this initiation codon has a low translation efficiency, and the cellular Hda level is only approximately 100 molecules per cell. Hda translated using the correct reading frame was purified and found to have a high RIDA activity in vitro. Moreover, we found that Hda has a high affinity for ADP but not for other nucleotides, including ATP. ADP-Hda was active in the RIDA system in vitro and stable in a monomeric state, whereas apo-Hda formed inactive homomultimers. Both ADP-Hda and apo-Hda could form complexes with the DNA-loaded clamp; however, only ADP-Hda-DNA-clamp complexes were highly functional in the following interaction with DnaA. Formation of ADP-Hda was also observed in vivo, and mutant analysis suggested that ADP binding is crucial for cellular Hda activity. Thus, we propose that ADP is a crucial Hda ligand that promotes the activated conformation of the protein. ADP-dependent monomerization might enable the arginine finger of the Hda AAA+ domain to be accessible to ATP bound to the DnaA AAA+ domain.

Utility of plasma circulating mRNA as a marker to detect hepatic injury.

Utility of plasma circulating mRNA as a molecular marker to detect hepatic injury was evaluated. Total RNA was isolated from plasma of the rat liver fibrosis models at various time points, and plasma circulating mRNAs of major liver-derived genes, albumin and haptoglobin, were measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Sensitivity and kinetics of plasma circulating mRNA were compared with those of plasma alanine aminotransferase (ALT) activity. We have found that the measurement of plasma circulating mRNA is more sensitive than plasma ALT activity, and enables early detection of hepatic injury. The plasma circulating mRNA will serve as a novel and highly sensitive molecular marker for hepatic injury.