Oxidative Cyclization at ortho-Position of Phenol: Improved Total Synthesis of 3-(Phenethylamino)demethyl(oxy)aaptamine.

A shorter synthesis of the demethyl(oxy)aaptamine skeleton was developed via oxidative intramolecular cyclization of 1-(2-azidoethyl)-6-methoxyisoquinolin-7-ol followed by dehydrogenation with a hypervalent iodine reagent. This is the first example of oxidative cyclization at the ortho-position of phenol that does not involve spiro-cyclization, resulting in the improved total synthesis of 3-(phenethylamino)demethyl(oxy)aaptamine, a potent anti-dormant mycobacterial agent.

Concurrent cerebral infarction and intracranial tuberculoma induced by the carotid plaque complicated with miliary tuberculosis.

Cerebrovascular complications of central nervous system tuberculosis (TB) are predictors of poor prognosis and adverse outcomes. These complications are mainly intracranial arterial involvement, with occasional venous involvement. Here, we present a 67-year-old woman with concurrent cerebral infarction and intracranial tuberculoma induced by the carotid plaque complicated by miliary tuberculosis. Mycobacterium tuberculosis was observed on the luminal side of the carotid plaques in pathological specimens. Treatment with anti-TB drugs alone would likely not cure the patient, as M. tuberculosis would continue to disseminate. Endarterectomy could directly remove the embolic source, and a complete cure was achieved.

The role of central corticotrophin-releasing factor receptor signalling in plasma glucose maintenance through ghrelin secretion in calorie-restricted mice.

Under severe calorie restriction (CR), the ghrelin-growth hormone axis in mice is involved in the maintenance of plasma glucose levels. Ghrelin, a stomach-derived acylated peptide, is up-regulated by the sympathetic nerve in the negative energy status. Central corticotrophin-releasing factor receptor (CRF-R) signalling stimulates the sympathetic tone. The present study aimed to examine the effect of central CRF-R signalling on the maintenance of plasma glucose concentrations in severe calorie-restricted mice with the involvement of ghrelin. Intracerebroventricular injections of urocorin-1 and urocorin-2, which are natural ligands for CRF-R1 and CRF-R2, elevated plasma ghrelin concentrations and ghrelin elevation with an i.c.v. injection of urocorin-1 was cancelled by atenolol (ß1 adrenergic receptor antagonist) administration. We then established a mice model of 60% CR and found that the administration of [d-Lys3]-GHRP-6 (a ghrelin receptor antagonist) in mice under 60% CR reduced the plasma glucose concentration more compared to the vehicle mice. Similarly, the atenolol injection in mice under 60% CR significantly reduced the plasma glucose concentration, which was rescued by the co-administration of ghrelin. An i.c.v. injection of the alpha helical CRH, a non-selective corticotrophin-releasing factor receptor antagonist, in mice under 60% CR significantly reduced the plasma glucose concentration, although the co-administration of α-helical CRH with ghrelin maintained plasma glucose levels. These results suggest that central CRF-R signalling is involved in the maintenance of plasma glucose levels in mice under severe CR via the sympathetic-ghrelin pathway.

[A case of drug-induced pneumonitis due to a cold remedy].

The patient was an 84-year-old woman who took a combination cold remedy, Shin-Rulu-A' for three days because of fever and cough. However, her symptoms worsened and she visited our hospital. Arterial blood gas analysis revealed severe hypoxemia and chest computed tomography showed diffuse ground glass opacities in both lungs. Analysis of bronchoalveolar lavage fluid disclosed an increased proportion of lymphocytes. The cold remedy was stopped, corticosteroids were administered, and she recovered. After positive results of lymphocyte stimulation testing to Shin-Rulu-A, a diagnosis of drug-induced pneumonitis was made. However the responsible ingredient was not established, because lymphocyte stimulation tests for each ingredient in Shin-Rulu-A were negative. To the best of our knowledge, this is the second report of Shin-Rulu-A-induced pneumonitis in Japan.

Pulmonary Reinfection by Nocardia in an Immunocompetent Patient with Bronchiectasis.

Pulmonary reinfection by Nocardia has been rarely reported. We describe a case of pulmonary reinfection by Nocardia in an immunocompetent patient. An 82-year-old immunocompetent woman with bronchiectasis presented with exacerbation of cough. She had a history of pulmonary nocardiosis three years earlier. At that time, Nocardia species were cultured from the sputum and identified as N. cyriacigeorgica with 16S ribosomal RNA gene sequencing. In the present episode, cultures of sputum and bronchial washing specimens grew N. beijingensis, which was identified with 16S ribosomal RNA gene sequencing. Pulmonary reinfection by different Nocardia species can occur in immunocompetent patients.

Association of serum levels of antibodies against MMP1, CBX1, and CBX5 with transient ischemic attack and cerebral infarction.

Transient ischemic attack (TIA) is a predictor for cerebral infarction (CI), and early diagnosis of TIA is extremely important for the prevention of CI. We set out to identify novel antibody biomarkers for TIA and CI, and detected matrix metalloproteinase 1 (MMP1), chromobox homolog 1 (CBX1), and chromobox homolog 5 (CBX5) as candidate antigens using serological identification of antigens by recombinant cDNA expression cloning (SEREX) and Western blotting to confirm the presence of serum antibodies against the antigens. Amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) revealed that serum antibody levels were significantly higher in patients with TIA or acute-phase CI (aCI) compared with healthy donors (P < 0.01). Spearman's correlation analysis and multivariate logistic regression analysis demonstrated that levels of anti-MMP1, anti-CBX1, and anti-CBX5 antibodies were associated with age, cigarette-smoking habits, and blood pressure. Thus, serum levels of antibodies against MMP1, CBX1, and CBX5 could potentially serve as useful tools for diagnosing TIA and predicting the onset of aCI.

Elevated Adiponectin Antibody Levels in Sera of Patients with Atherosclerosis-Related Coronary Artery Disease, Cerebral Infarction and Diabetes Mellitus.

Adiponectin secreted from the adipocytes plays pleiotropic, anti-atherosclerotic roles, such as enhancement of insulin secretion and an increase in energy expenditure. The measurement of levels of circulating adiponectin is useful to evaluate the progression of atherosclerosis-related diseases, such as coronary artery disease (CAD), cerebral infarction (CI) and diabetes mellitus (DM). We examined the serum antibody levels against recombinant adiponectin protein via the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) method. The results revealed that the antibody levels were significantly higher in patients with CAD, CI and type 2 DM, than in healthy donors. Receiver operating curve analysis showed that the sensitivity was in a range of 41-48% for CAD, CI and DM. Thus, the serum anti-adiponectin antibody levels could be a common marker for atherosclerosis-related diseases.

Effect of a brief training program based on cognitive behavioral therapy in improving work performance: A randomized controlled trial.

OBJECTIVES: Efforts to improve performance in the workplace with respect to positive mental health have increased, and cognitive behavioral therapy (CBT) has recently attracted attention as an intervention measure to this end. Here, we conducted a randomized controlled trial to evaluate the effectiveness of a brief training program on CBT for improving work performance of employees. METHODS: The participants were employees of an electric company in Japan. The intervention consisted of 1 group session of CBT (120 min) and web-based CBT homework for 1 month. We evaluated employees in both the intervention and control groups at baseline and follow-up after three months. The main outcome was work performance, which was evaluated by a subjective score from 1 to 10. The secondary outcome was self-evaluation of cognitive flexibility. Analyses were conducted based on ITT. RESULTS: In the intervention group, 84 participants attended the group session, with 79 subsequently completing at least 1 instance of online homework. ITT analysis showed that the subjective performance of the intervention group was significantly improved compared with that of the control group (1.47 vs. 0.69, mean difference 0.78 [95% confidence interval {CI}, 0.05 to 1.51], Cohen's d=0.31). The ability to recognize dysfunctional thinking patterns and change them to positive ones significantly improved in the intervention group compared to the control group (0.71 vs. 0.26, mean difference 0.45 [95% CI 0.06 to 0.83], d=0.33). However, after adjustment for baseline scores, no significant difference was observed. The ability to view a situation from multiple perspectives and expand one's repertoire of thought patterns in the intervention group also significantly improved (0.83 vs. 0.35, mean difference 0.48 [95% CI 0.35 to 0.95], d=0.29), but here again, significance was lost after adjusting for baseline scores. DISCUSSION: Our results suggest that a brief training program that combines a group CBT session with web-based CBT homework improved subjective work performance. In addition, this program might help improve employees' cognitive flexibility.

A web-based training program using cognitive behavioral therapy to alleviate psychological distress among employees: randomized controlled pilot trial.

BACKGROUND: A number of psychoeducational programs based on cognitive behavioral therapy (CBT) to alleviate psychological distress have been developed for implementation in clinical settings. However, while these programs are considered critical components of stress management education in a workplace setting, they are required to be brief and simple to implement, which can hinder development. OBJECTIVE: The intent of the study was to examine the effects of a brief training program based on CBT in alleviating psychological distress among employees and facilitating self-evaluation of stress management skills, including improving the ability to recognize dysfunctional thinking patterns, transform dysfunctional thoughts to functional ones, cope with stress, and solve problems. METHODS: Of the 187 employees at an information technology company in Tokyo, Japan, 168 consented to participate in our non-blinded randomized controlled study. The training group received CBT group education by a qualified CBT expert and 1 month of follow-up Web-based CBT homework. The effects of this educational program on the psychological distress and stress management skills of employees were examined immediately after completion of training and then again after 6 months. RESULTS: Although the training group did exhibit lower mean scores on the Kessler-6 (K6) scale for psychological distress after 6 months, the difference from the control group was not significant. However, the ability of training group participants to recognize dysfunctional thinking was significantly improved both immediately after training completion and after 6 months. While the ability of participants to cope with stress was not significantly improved immediately after training, improvement was noted after 6 months in the training group. No notable improvements were observed in the ability of participants to transform thoughts from dysfunctional to functional or in problem-solving skills. A sub-analysis of participants who initially exhibited clinically significant psychological distress (K6 score ≥5) showed that the mean K6 score was significantly improved immediately after training completion for the training group compared to the control group (-2.50 vs -0.07; mean difference 2.43, 95% CI 0.55-4.31; d=0.61), with this effect remaining even after 6 months (-3.49 vs -0.50; mean difference 2.99, 95% CI 0.70-5.29; d=0.60). CONCLUSIONS: Our results suggest that a brief stress management program that combines group CBT education with Web-based CBT homework moderately alleviates the distress of employees with clinically significant psychological distress. In addition, the program might help improve employees' ability to evaluate their own stress management skills.

2-Cys peroxiredoxin of Plasmodium falciparum is involved in resistance to heat stress of the parasite.

In the cytoplasm of Plasmodium falciparum, two peroxiredoxins: PfTPx-1 and Pf1-Cys-Prx, are expressed at different time-points of the parasite cell cycle during the intraerythrocytic stage. In the present study, to gain insight into the functions of Prxs in the cytoplasm of P. falciparum, we investigated the heat stress sensitivity of the previously established PfTPx-1 KO line and found that PfTPx-1 disruption renders the parasite hypersensitive to heat stress. In addition, we established Pf1-Cys-Prx knockout (KO) parasite lines. The phenotypes of Pf1-Cys-Prx KO lines were different to those of the PfTPx-1 KO line and did not show hypersensitivity to reactive oxygen species, reactive nitrogen species, chloroquine or heat stress. These results suggest that the function of Pf1-Cys-Prx in the parasite cytoplasm is independent from that of PfTPx-1. The hyperthermal protective function of the PfTPx-1 is obviously important for the parasite physiology in the human patient body, in which it must survive repeated incidences of fever.