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Background There are ongoing efforts to examine the effect of 5-HT1A receptor partial agonists as an add-on therapy for several symptoms of schizophrenia. By conducting a systematic review and meta-analysis, we evaluated whether augmentation with 5-hydroxtrypatamine (5-HT)1A partial agonists of the azapirone class improves psychotic symptoms and attention/processing speed, a key domain of cognition, in patients with schizophrenia. Methods A literature search was performed from 1987 to February 25, 2022, to identify randomized controlled trials. The standardized mean difference (SMD) with 95% confidence intervals (CI) was calculated when there were 2 or more studies. Seven studies, involving 435 patients, met the inclusion criteria. Results Random-effects model meta-analyses revealed that add-on therapy with buspirone or tandospirone had a significant beneficial effect on overall psychotic symptoms (SMD = –1.13, 95% CI = –1.98 to –0.27) and positive symptoms (SMD = –0.72, 95% CI =–1.31 to –0.12), while the effect on negative symptoms did not reach statistical significance (SMD = –0.93, 95% CI = –1.90 to 0.04). A significant positive effect was also observed on attention/processing speed (SMD = 0.37, 95% CI = 0.12 to 0.61). Conclusions These findings support the idea that some compounds that stimulate 5-HT1A receptors provide an effective pharmacologic enhancer in the treatment of schizophrenia. Further clinical trials are warranted to determine the benefits of the adjunctive use of 5-HT1A partial agonists in ameliorating symptoms and improving functional outcomes in patients with schizophrenia or other psychiatric disorders.

BackgroundThe number of people with dementia in Japan will estimate to increase to roughly 20% of those aged 65 and over (approximately 7 million people) by 2025. Around the world, the number of people with dementia is increasing by 7.7 million per year, and caregivers’ depression, stress, social isolation, and sleep disorders due to the burden of caregiving are also increasing. Economic losses worldwide due to physical and mental health problems of dementia caregivers, reduced work hours due to caregiving, and job loss are estimated to be $252 billion in 2010. In addition, the risk of abuse against the caregiver increases as the caregiver is affected by physical and mental illness. Psychosocial interventions such as cognitive behavioral therapy have reportedly reduced caregivers’ mental distress and improved their health. Since caregivers have significant time and physical limitations due to caregiving, it is promising that interventions using the internet, which have few limitations in terms of location and time, will be helpful, along with its low cost.MethodsThis is a two-arm, randomized, waitlist-controlled trial. Participants will be randomized with a 1:1 ratio to either the immediate or late access group. The early intervention group will be able to use iSupport for three months, followed by allocation and follow-ups until six months. In the waitlist group, iSupport can be available for three months from the end of the Month 3 evaluation. Scheduled evaluation periods are Months 1, 3, and 6.DiscussionWe plan to begin recruiting for the trial in January 2021. We plan to finish the inclusion by June 2021 and complete all data collection by December 2021. Once all data collection is complete, we plan to analyze the data by April 2022; we aim to publish the results in a manuscript by the end of 2022.Trial RegistrationUMIN-CTR, UMIN000042957, registered on January 9, 2021.

BackgroundBoth impairment and sex differences in social cognition and neurocognition have been documented in schizophrenia. However, whether sex differences exist in the association between social cognition and neurocognition are not known. We aimed to investigate the contribution of areas of neurocognition to theory of mind (ToM) and hostility bias, representing social cognition, according to sex in early course schizophrenia.MethodsIn this cross-sectional study, we assessed neurocognition using the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS) and assessed the ToM and hostility bias subdomains of social cognition using the Social Cognition Screening Questionnaire (SCSQ) in 131 participants (65 female, 66 male) diagnosed with schizophrenia within 5 years of onset. Sex differences were analyzed usingt-tests. The associations of neurocognitive subdomains with ToM and hostility bias according to sex were analyzed using multiple regression analysis. Results were adjusted by age, estimated premorbid intelligence quotient, and symptomatology.ResultsNo sex differences were found in ToM (p= 0.071) or hostility bias (p= 0.057). Higher verbal fluency was significantly associated with higher ToM in females (p< 0.01), whereas higher executive function was significantly associated with higher ToM in males (p< 0.05). Higher verbal fluency was significantly associated with lower hostility bias in females (p< 0.05), whereas neurocognition and hostility bias were not significantly associated in males.ConclusionThe results suggest that neurocognition associated with social cognition differ according to sex. These differences should be considered for more effective treatment of social cognition.

Backgrounds: Social cognition is defined as the mental operations underlying social behavior. Patients with schizophrenia elicit impairments of social cognition, which is linked to poor real-world functional outcomes. In a previous study, transcranial direct current stimulation (tDCS) improved emotional recognition, a domain of social cognition, in patients with schizophrenia. However, since social cognition was only minimally improved by tDCS when administered on frontal brain areas, investigations on the effect of tDCS on other cortical sites more directly related to social cognition are needed. Therefore, we present a study protocol to determine whether multi-session tDCS on superior temporal sulcus (STS) would improve social cognition deficits of schizophrenia. Methods: This is an open-label, single-arm trial, whose objective is to investigate the efficacy and safety of multi-session tDCS over the left STS to improve social cognition in patients with schizophrenia. The primary outcome measure will be the Social Cognition Screening Questionnaire. Neurocognition, functional capacity, and psychotic symptoms will also be evaluated by the Brief Assessment of Cognition in Schizophrenia, UCSD Performance-Based Skills Assessment-Brief, and Positive and Negative Syndrome Scale, respectively. Data will be collected at baseline, and 4 weeks after the end of intervention. If social cognition is improved in patients with schizophrenia by tDCS based on this protocol, we may plan randomized controlled trial.

Pseudomonas putida KT2440 (hereafter KT2440) is a well-studied platform bacterium for the production of industrially valuable chemicals from heterogeneous mixtures of aromatic compounds obtained from lignin depolymerization. KT2440 can grow on lignin-related monomers, such as ferulate (FA), 4-coumarate (4CA), vanillate (VA), 4-hydroxybenzoate (4HBA), and protocatechuate (PCA). Genes associated with their catabolism are known, but knowledge about the uptake systems remains limited. In this work, we studied the KT2440 transporters of lignin-related monomers and their substrate selectivity. Based on the inhibition by protonophores, we focused on five genes encoding aromatic acid/H+ symporter family transporters categorized into major facilitator superfamily that uses the proton motive force. The mutants of PP_1376 (pcaK) and PP_3349 (hcnK) exhibited significantly reduced growth on PCA/4HBA and FA/4CA, respectively, while no change was observed on VA for any of the five gene mutants. At pH 9.0, the conversion of these compounds by hcnK mutant (FA/4CA) and vanK mutant (VA) was dramatically reduced, revealing that these transporters are crucial for the uptake of the anionic substrates at high pH. Uptake assays using 14C-labeled substrates in Escherichia coli and biosensor-based assays confirmed that PcaK, HcnK, and VanK have ability to take up PCA, FA/4CA, and VA/PCA, respectively. Additionally, analyses of the predicted protein structures suggest that the size and hydropathic properties of the substrate-binding sites of these transporters determine their substrate preferences. Overall, this study reveals that at physiological pH, PcaK and HcnK have a major role in the uptake of PCA/4HBA and FA/4CA, respectively, and VanK is a VA/PCA transporter. This information can contribute to the engineering of strains for the efficient conversion of lignin-related monomers to value-added chemicals.

The damage caused by the pirated films amounts to $1.3 billion a year. The pirated films are mainly created by re-shooting a screen in a theater or duplicating the official DVDs. Films are released in a theater. Before the official DVDs are released, 90% of the films are pirated in a theater and illegally made DVDs are sold. Although counter technologies are required, there is no effective proposals. The important requirement for the technology is that it does not degrade the image quality in a theater. It only degrades the re-shot video. In this paper, we report a novel method to make it possible.