Sulfanylmethyldimethylaminopyridine as a Useful Thiol Additive for Ligation Chemistry in Peptide/Protein Synthesis

Sulfanylmethyl-installed dimethylaminopyridine, 2-sulfanylmethyl-4-dimthylaminopyridine (SMDMAP) (2), has an acidic thiol group comparable to that in aryl thiols due to the formation of a zwitterion consisting of a thiolate anion and a pyridinium cation. It can be used as an additive for native chemical ligation. The alkyl thiol in 2 allows it to be used for the one-pot/NCL–desulfurization protocol in peptide synthesis. The utility of 2 in the synthesis of cyclic peptides is demonstrated

The effects of cognitive remediation therapy using the frontal/executive program for autism spectrum disorder

Objective: The cognitive features and treatment of autism spectrum disorder have been the subject of much debate in recent years. Therapeutic approaches to date have focused on skills acquisition, support tailored to the characteristics of autism spectrum disorder, and interventions in social cognitive functioning; there have been few reports describing interventions aimed at neurocognitive dysfunction. In this study, we focus on impairment of executive functioning in autism spectrum disorder patients and investigate improvements in executive functioning and their generalization to social functioning. Method: The intervention adopted for this study was cognitive remediation therapy using the frontal/executive program. To investigate the effectiveness of frontal/executive program, 15 subjects who consented to participate in the study were randomly assigned to an intervention group or control group. Frontal/executive program was administered to the intervention group for about six months. Both groups were evaluated using the same scales: BACS-J, WCST, and CPT for cognitive assessment; SCoRS-J, GAF, and LASMI for social functioning; and GSE for self-efficacy. Results: Both groups had lower scores for cognitive functioning than normal individuals at baseline. After completion of frontal/executive program, the intervention group showed improved performance on BACS-J for overall score, digit sequencing, verbal fluency, and Tower of London tasks. Improvements were also seen on SCoRS-J and LASMI scales of social functioning. Conclusions: This was the first study to use frontal/executive program to focus on neurocognitive dysfunction in autism spectrum disorder patients. Frontal/executive program is effective in improving impaired executive functioning in autism spectrum disorder patients and may also lead to improvements in some aspects of social functioning

Association between COVID-19 vaccine hesitancy and generalized trust, depression, generalized anxiety, and fear of COVID-19

Background!#!Although numerous studies have been published on the predictors of COVID-19 vaccine hesitancy, some possible predictors remain underexplored. In this study, we explored the associations of unwillingness and indecisiveness regarding COVID-19 vaccination with generalized trust, mental health conditions such as depression and generalized anxiety, and fear of COVID-19.!##!Methods!#!Data of wave 1 (from October 27 till November 6, 2020) and wave 3 (from April 23 till May 6, 2021) of a longitudinal online study conducted in Japan were used for the analyses. Unvaccinated participants were asked at wave 3 about their willingness to be vaccinated, with possible responses of willing, unwilling, or undecided. These three responses were used as the outcome variable, and multinomial logistic regression analyses were conducted with willingness to be vaccinated as the reference group. Explanatory variables included generalized trust, depression, generalized anxiety, and fear of COVID-19 both at wave 1 and 3, and sociodemographic and health-related variables.!##!Results!#!Of the 11,846 valid respondents, 209 (1.8%) answered that they had already been vaccinated against COVID-19, 7089 (59.8%) responded that they were willing to be vaccinated, 3498 (29.5%) responded that they were undecided, and 1053 (8.9%) responded that they were unwilling to be vaccinated. After adjusting for covariates, we found that: (1) participants with lower levels of generalized trust at wave 1 and 3 were more likely to be undecided or unwilling at wave 3; (2) respondents with moderately severe or severe depression at wave 1 and 3 were more likely to be undecided at wave 3; (3) participants with moderate or severe levels of generalized anxiety at wave 3 but not at wave 1 were more likely to be unwilling at wave 3; and (4) respondents with high levels of fear of COVID-19 at wave 1 and 3 were less likely to be undecided and unwilling at wave 3.!##!Conclusions!#!Generalized trust, mental health conditions such as depression and generalized anxiety, and low level of fear of COVID-19 are associated with unwillingness or indecision regarding being vaccinated against COVID-19

Long-term outcome of antidepressant-refractory depression: The relevance of unrecognized bipolarity

Background: The long-term outcome of antidepressant-refractory depression is not well known. Therefore, the present study investigated the long-term outcome of 26 antidepressant-refractory patients with depression, whom we had studied and treated in 1995. Methods: Before being classified as nonresponse, these patients had been treated adequately with at least two tricyclic or heterocyclic antidepressants (a minimum of the equivalent of 150mg of imipramine for 4 weeks). In 1995, 21 of 26 patients were diagnosed with unipolar depression, while 5 were diagnosed with bipolar depression. Mean follow-up was 5.7 years (range: 1–7 years) and changes in diagnosis, remission and treatment efficacy were evaluated. Results: Following the long-term follow-up, 13 patients achieved full remission and demonstrated high social functioning (mean GAF score, 91). A further four depressed patients experienced full remission; however, subsequent recurrence was observed. In total, 17 of 26 patients experienced remission at least once during the long-term follow-up period despite the chronic depressive episodes observed at study entry. Adjuvant treatment with lithium, dopamine receptor agonists or thyroid hormone was effective for promoting full remission. Among the 21 patients initially diagnosed with unipolar depression in 1995, diagnoses were changed to bipolar disorder in 5 cases. Limitations: This naturalistic study had a relatively small sample size and treatment was not controlled. Conclusions: Long-term follow-up revealed that a substantial proportion of antidepressant-refractory depression is comprised of bipolar disorders. In addition, augmentation therapies are effective for promoting full remission among chronically depressed patients without a risk of serious side effects

Therapeutic responses to a frontal/executive programme in autism spectrum disorder: Comparison with schizophrenia

Introduction Studies on autism spectrum disorder in recent years have controversially indicated similarities with schizophrenia. Cognitive dysfunction is present in both disorders, and while there is a rich array of interventions for cognitive dysfunction in schizophrenia, there are few such treatments for autism spectrum disorder. In this study, we have investigated a potentially useful approach in autism spectrum disorder by comparing autism spectrum disorder with schizophrenia in regard to the characteristics of cognitive dysfunction and therapeutic response to cognitive remediation therapy. Method We studied seven patients with autism spectrum disorder and eight patients with schizophrenia, using a frontal/executive programme as the intervention. The characteristics of cognitive dysfunction in autism spectrum disorder before frontal/executive programme and the therapeutic response to frontal/executive programme in autism spectrum disorder patients were compared with those in schizophrenia patients, based on evaluation of cognitive function and social function. The changes in cognitive and social function after treatment in each patient group were compared using the Mann–Whitney’s U test. Results The severity of cognitive dysfunction did not differ significantly between autism spectrum disorder and schizophrenia. Frontal/executive programme was effective in autism spectrum disorder, with subjects showing about the same therapeutic response as in schizophrenia. Conclusion Frontal/executive programme appears to be useful for patients with autism spectrum disorder. Furthermore, the similarities in cognitive dysfunction and therapeutic response between autism spectrum disorder and schizophrenia are highly relevant to the recent debate concerning the similarity between these two disease concepts