Acceleration of hydrolytic ring opening of N7-alkylguanine by the terminal carbamoyl group of glycidamide.

Hydrolytic ring opening of guanine N7-adducts with compounds containing an oxacyclopropane ring, namely glycidamide, glycidol and 1,2-epoxybutane, was analyzed, and the reaction of the glycidamide adduct was the fastest. The differences in the reaction rates were confirmed by theoretical calculations.

Prediction of decline in activities of daily living using motor performance tests in older adults requiring long-term care.

OBJECTIVE: This study aimed to predict decline in activities of daily living (ADL) in older adults requiring long-term care, using motor performance tests. METHODS: This prospective cohort study was conducted among 3948 older adults using day care services in Japan. ADL decline was assessed using the Functional Independence Measure at the start of day care service use and 12 months later. Grip strength (GS), one-leg standing (OLS), and comfortable walking speed (CWS) were measured as baseline motor performance tests. To predict ADL decline using motor performance tests, we calculated cut-off values using receiver operating characteristics curves and odds ratios using logistic regression analysis. RESULTS: In total, 521 participants had ADL decline at 12 months of follow-up. The cut-off values for each motor performance test were as follows (for men/women): GS < 24 kg/16 kg, OLS < 2 s/3 s, and CWS < 0.77 m/s/0.71 m/s. The odds ratios based on the number of items with scores below the cut-off were 1.84 for one item, 3.19 for two items, and 5.20 for three items. CONCLUSION: Motor performance tests are effective in predicting ADL decline in older adults requiring long-term care, and combining the results of multiple items is even more effective.

Bacille Calmette-Guérin Vaccine-Induced Tuberculous Elbow Osteomyelitis in an Infant: A Case Report.

CASE: We report a case of Bacillus Calmette-Guérin (BCG) vaccine-induced osteomyelitis of the distal end of the right humerus in a 1-year and 8-month-old girl. The patient was treated with debridement and a 12-month antituberculosis drug. After 3 years of follow-up, no growth disturbances or sequelae were observed. CONCLUSION: BCG osteomyelitis is difficult to diagnose because of its rarity. It is important to suspect BCG osteomyelitis based on symptoms and blood tests and to perform PCR testing. Long-term follow-up after treatment is necessary to monitor for recurrence and avoid growth disturbances until epiphyseal line closure occurs.

Preliminary Evaluation of Translated and Culturally Adapted Internet-Delivered Cognitive Therapy for Social Anxiety Disorder: Multicenter, Single-Arm Trial in Japan.

BACKGROUND: Internet-delivered cognitive therapy for social anxiety disorder (iCT-SAD), which is a therapist-guided modular web-based treatment, has shown strong efficacy and acceptability in English-language randomized controlled trials in the United Kingdom and Hong Kong. However, it is not yet known whether iCT-SAD can retain its efficacy following linguistic translation and cultural adaptation of treatment contents and implementation in other countries such as Japan. OBJECTIVE: This study aimed to examine the preliminary efficacy and acceptability of the translated and culturally adapted iCT-SAD in Japanese clinical settings. METHODS: This multicenter, single-arm trial recruited 15 participants with social anxiety disorder. At the time of recruitment, participants were receiving usual psychiatric care but had not shown improvement in their social anxiety and required additional treatment. iCT-SAD was provided in combination with usual psychiatric care for 14 weeks (treatment phase) and for a subsequent 3-month follow-up phase that included up to 3 booster sessions. The primary outcome measure was the self-report version of the Liebowitz Social Anxiety Scale. The secondary outcome measures examined social anxiety-related psychological processes, taijin kyofusho (the fear of offending others), depression, generalized anxiety, and general functioning. The assessment points for the outcome measures were baseline (week 0), midtreatment (week 8), posttreatment (week 15; primary assessment point), and follow-up (week 26). Acceptability was measured using the dropout rate from the treatment, the level of engagement with the program (the rate of module completion), and participants' feedback about their experience with the iCT-SAD. RESULTS: Evaluation of the outcome measures data showed that iCT-SAD led to significant improvements in social anxiety symptoms during the treatment phase (P<.001; Cohen d=3.66), and these improvements were maintained during the follow-up phase. Similar results were observed for the secondary outcome measures. At the end of the treatment phase, 80% (12/15) of participants demonstrated reliable improvement, and 60% (9/15) of participants demonstrated remission from social anxiety. Moreover, 7% (1/15) of participants dropped out during treatment, and 7% (1/15) of participants declined to undergo the follow-up phase after completing the treatment. No serious adverse events occurred. On average, participants completed 94% of the modules released to them. Participant feedback was positive and highlighted areas of strength in treatment, and it included further suggestions to improve suitability for Japanese settings. CONCLUSIONS: Translated and culturally adapted iCT-SAD demonstrated promising initial efficacy and acceptability for Japanese clients with social anxiety disorder. A randomized controlled trial is required to examine this more robustly.

Antecedents and Outcomes of Work Engagement among Psychiatric Nurses in Japan.

While previous studies have examined antecedents and outcomes of work engagement among general nurses, studies among psychiatric nurses remain limited. This study aimed to explore the antecedents (i.e., job crafting and nursing practice environment) and outcomes (i.e., strength-oriented care attitudes, mental health, and turnover intention) of work engagement among psychiatric nurses in Japan. This cross-sectional study included 309 nurses from three psychiatric hospitals in Japan (valid response rate: 60.4%). Data collection using the self-administered questionnaire took place from July to August 2021. We performed Structural Equation Modeling to examine the directional relationships among variables. Job crafting (ß = 0.57, p < 0.01) and nursing practice environment (ß = 0.23, p = 0.01) exhibited positive effects on work engagement. Work engagement had positive effects on strength-oriented care attitudes (ß = 0.15, p = 0.04) and mental health (ß = 0.37, p < 0.01) as well as negative effects on intention to resign from their profession as a nurse (ß = -0.17, p = 0.01). Job crafting and a healthier nursing practice environment could help enhance work engagement. Higher work engagement could contribute to improving strength-oriented care attitudes, mental health, and intention to resign from their profession as a nurse.

Electrogenerated base-promoted cyclopropanation using alkyl 2-chloroacetates.

The electrochemical reduction conditions of the reaction of alkyl 2-chloroacetates in Bu4NBr/DMF using a divided cell equipped with Pt electrodes to produce the corresponding cyclopropane derivatives in moderate yields were discovered. The reaction conditions were optimized, the scope and limitations, as well as scale-up reactions were investigated. The presented method for the electrochemical production of cyclopropane derivatives is an environmentally friendly and easy to perform synthetic procedure.

Naturalistic outcome of nurse-led psychological therapy for mental disorders in routine outpatient care: A retrospective chart review.

This study aimed to investigate the clinical effectiveness of nurse-led cognitive/behavioral therapy (CBT) in Japanese routine outpatient care. We retrospectively collected data from 100 cases with mental disorders who had received nurse-led CBT. Results demonstrated that CBT provided by nurses led to significant improvements in quality of life and other clinical outcomes during the intervention period (all p < 0.001). Among participants who received optional follow-up, these improvements were well-maintained. This real-world evidence of nurse-led CBT bridges the research-practice gap, and will encourage frontline nurses and motivate institutional/organizational leaders, academic/professional societies, and policymakers to employ empirically-supported psychotherapeutic techniques in routine nursing care.

Tendon-Specific Dicer Deficient Mice Exhibit Hypoplastic Tendon Through the Downregulation of Tendon-Related Genes and MicroRNAs.

Tendon is a fibrous connective tissue, that is, transmitting the forces that permit body movement. However, tendon/ligament biology is still not fully understood and especially, the role of miRNAs in tendon/ligament is sparse and uncharacterized in in vivo models. The objectives of this study were to address the function of DICER using mice with tendon/ligament-specific deletion of Dicer (Dicer conditional knockout; cKO), and to identify key miRNAs in tendon/ligament. Dicer cKO mice exhibited hypoplastic tendons through structurally abnormal collagen fibrils with downregulation of tendon-related genes. The fragility of tendon did not significantly affect the tensile strength of tendon in Dicer cKO mice, but they showed larger dorsiflexion angle in gait compared with Control mice. We identified two miRNAs, miR-135a and miR-1247, which were highly expressed in the Achilles tendon of Control mice and were downregulated in the Achilles tendon of Dicer cKO mice compared with Control mice. miR-135a mimic increased the expression of tendon-related genes in injured Achilles tendon-derived fibroblasts. In this study, Dicer cKO mice exhibited immature tendons in which collagen fibrils have small diameter with the downregulation of tendon-related genes such as transcriptional factor, extracellular matrix, and miRNAs. Thus, DICER plays an important role in tendon maturation, and miR-135a may have the potential to become key miRNA for tendon maturation and healing.

Conformationally Fixed Chiral Bisphosphine Ligands by Steric Modulators on the Ligand Backbone: Selective Synthesis of Strained 1,2-Disubstituted Chiral cis-Cyclopropanes.

A new series of C1-symmetric P-chirogenic bisphosphine ligands of the type (R)-5,8-Si-Quinox-tBu3 (Silyl = SiMe3, SiEt3, SiMe2Ph) have been developed. The bulky silyl modulators attached to the ligand backbone fix the phosphine substituents to form rigid chiral environments that can be used for substrate recognition. The ligand showed high performances for a copper(I)-catalyzed asymmetric borylative cyclopropanation of bulky silyl-substituted allylic electrophiles to afford higher disfavored 1,2-cis-silyl-boryl-cyclopropanes than the other possible isomers, trans-cyclopropane and allylboronate (up to 97% yield; 98% ee; cis/trans = >99:1; cyclopropane/allylboronate = >99:1). Detailed computational studies suggested that the highly rigid phosphine conformation, which is virtually undisturbed by the steric interactions with the bulky silyl-substituted allyl electrophiles, is key to the high stereo- and product-selectivities. Furthermore, the detailed computational analysis provided insight into the mechanism of the stereoretention or -inversion of the chiral alkylcopper(I) intermediate in the intramolecular cyclization.

The therapeutic capacity of bone marrow MSC-derived extracellular vesicles in Achilles tendon healing is passage-dependent and indicated by specific glycans.

The therapeutic potential of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) for various diseases and tissue repair is attracting attention. Here, EVs from conditioned medium of human bone marrow MSCs at passage 5 (P5) and passage 12 (P12) were analysed using mouse Achilles tendon rupture model and lectin microarray. P5 MSC-EVs accelerated Achilles tendon healing compared with P12 MSC-EVs. Fucose-specific lectin TJA-II was indicated as a glycan marker for therapeutic MSC-EVs. The present study demonstrated that early passaged MSC-EVs promote Achilles tendon healing compared with senescent MSC-EVs. Glycans on MSC-EVs might provide useful tools to establish a quality control and isolation system for therapeutic MSC-EVs in regenerative medicine.

Enhancement of the mechanical and thermal transport properties of carbon nanotube yarns by boundary structure modulation.

Carbon nanotubes (CNTs) exhibit extremely high nanoscopic thermal/electrical transport and mechanical properties. However, the macroscopic properties of assembled CNTs are significantly lower than those of CNTs because of the boundary structure between the CNTs. Therefore, it is crucial to understand the relationship between the nanoscopic boundary structure in CNTs and the macroscopic properties of the assembled CNTs. Previous studies have shown that the nanoscopic phonon transport and macroscopic thermal transport in CNTs are improved by Joule annealing because of the improved boundary Van-der-Waals interactions between CNTs via the graphitization of amorphous carbon. In this study, we investigate the mechanical strength and thermal/electrical transport properties of CNT yarns with and without Joule annealing at various temperatures, analyzing the phenomena occurring at the boundaries of CNTs. The obtained experimental and theoretical results connect the nanoscopic boundary interaction of CNTs in CNT yarns and the macroscopic mechanical and transport properties of CNT yarns.

Arthroscopic mobilization for metacarpophalangeal joint extension contracture.

BACKGROUND: As a first-line surgical treatment for treating metacarpophalangeal (MCP) joint extension contractures, mobilization surgery with open dorsal approach has been indicated. However, this procedure has the possibility to result in postoperative recurrence over the course of time because its invasive open dorsal approach has a negative impact on the postoperative gliding of the extensor mechanism. We report the preliminarily outcomes of patients who underwent a minimally invasive arthroscopic mobilization to alter and enhance their existing surgical strategy in place of MCP joint extension contractures. METHODS: This retrospective study included seven patients with 13 MCP joint extension contractures who had received an arthroscopic release of the bilateral collateral ligament and/or dorsal capsule of affected MCP joint. The extension contractures were caused by long-time immobilization with inadequate extended position of the MCP joint after either hand and wrist fractures, extensor tendon injury, or peripheral nerve palsy. All patients received sufficient exercise under the supervision of a physical therapist for more than 3 months before surgery. However, physical therapy did not improve the MCP joint extension contractures. We measured the active and passive flexion angles preoperatively at 1 and 6 months after surgery. The passive flexion angle was also measured after arthroscopic mobilization on the operation table. Surgery-related complications regarding nerve, vessel, skin, and tendon were also assessed. RESULTS: In all patients, significant improvements were observed in both the active and passive flexion angles 1 month after surgery, and continued to improve 6 months after surgery. Two out of 13 metacarpophalangeal joints developed blisters on the dorsal side of the joint, but conservatively recovered. CONCLUSIONS: Based on the positive improvements observed in our patients, we conclude that this minimally invasive arthroscopic technique has the potential to alter and enhance the surgical treatment strategy for MCP joint extension contractures.

Solid-State C-N Cross-Coupling Reactions with Carbazoles as Nitrogen Nucleophiles Using Mechanochemistry.

The palladium-catalyzed solid-state C-N cross-coupling of carbazoles with aryl halides via a high-temperature ball-milling technique has been reported. This reaction allowed simple, fast, and efficient synthesis of N-arylcarbazole derivatives in good to excellent yields without the use of large amounts of organic solvents in air. Importantly, the developed solid-state coupling approach enabled the cross-coupling of poorly soluble aryl halides with large polyaromatic structures that are barely reactive under conventional solution-based conditions.

Correlates of improvement in the care need levels of older adults with disabilities: a two-year follow-up study.

[Purpose] This study examined the effect of motor functioning, cognitive functioning, and activities of daily living on improvements in care need levels of older adults requiring low-level care at baseline in Japan's Long-Term Care Insurance system. We aimed to link our findings to a proposal for effective measures toward improving care need levels. [Participants and Methods] This retrospective cohort study included 11,585 individuals aged 65 years and above who received personal care and used day-care services continuously for two or more years starting from the baseline assessment. Participants showing an improvement in their care need level from baseline to two years were included in the improved group, and those who maintained or declined from the baseline level were included in the maintained/deteriorated group. [Results] The mental status questionnaire and sub-scores for the Functional Independence Measure, including those for self-care, continence, and social cognition, were significantly correlated with improvements in care need levels. [Conclusion] Conducting a detailed evaluation of these factors is important for gauging the progress of the care need levels of older adults.In addition, it is important for physiotherapists to provide non-rehabilitation professionals with advice and guidance on their assessment methods and remedies.

Mobility performance impacts mortality risk in community-dwelling healthy older adults in Japan: a prospective observational study.

BACKGROUND: The timed up and go (TUG) test assesses balance and mobility performance. AIM: This study aims to investigate the association between TUG time and mortality in Japanese older persons and to clarify possible moderation effects on mortality and TUG time. METHODS: In all, 874 participants who were ≥ 65 years of age completed the TUG test and had their anthropometric parameters and physical functions measured. We investigated the association between all-cause mortality and TUG using a Cox regression model that included confounders, and explored the time associated with mortality using a restricted cubic spline. We also performed subgroup analyses to explore whether age, sex, and body mass index (BMI) affected the relationship between TUG time and mortality. RESULTS: The median age and mean follow-up period were 74 and 8.5 years, respectively. Median TUG time was 7.4 s and the prevalence of mortality was 25.7%. TUG time in one second was positively associated with an increased risk of total mortality [hazard ratio (HR): 1.054 (1.016-1.093); P = 0.005] in the Cox regression model. The positive association of mortality and TUG time was present when the TUG was over 10.5 s in the restricted cubic spline curve. Older age (75 years or older) moderated the relationship between TUG time and mortality [Pinteraction = 0.096]. CONCLUSION: This study demonstrates that TUG time is associated with all-cause mortality in Japanese older adults.

Extensive Lung Resection for Nontuberculous Mycobacterial Lung Disease With Multilobar Lesions.

BACKGROUND: Nontuberculous mycobacterial lung disease often spreads to multiple lobes, and extensive lung resection (ELR) is sometimes required to control the disease. The safety and feasibility of ELR for nontuberculous mycobacterial lung disease remain unclear, however. METHODS: This retrospective study included patients with nontuberculous mycobacterial lung disease who underwent adjuvant lung resection. Characteristics were compared between patients who underwent ELR and those who underwent simple anatomic lung resection (SALR). The outcome data were analyzed by a Cox regression analysis. RESULTS: A total of 146 patients underwent ELR (n = 54) or SALR (n = 92). ELR was associated with a longer operative time (306 vs 237 minutes; P < .001) and higher incidence of prolonged air leak (17% vs 3.3%; P = .016) than SALR. Rates of mortality, sputum culture conversion (positive to negative), and microbiological recurrence did not differ markedly between the groups. In the multivariate analysis, ELR was not a significant risk factor for an unfavorable outcome after nontuberculous mycobacterial lung disease surgery (hazard ratio, 2.23; 95% confidence interval, 0.82-6.03; P= .11). CONCLUSIONS: ELR for nontuberculous mycobacterial lung disease has some drawbacks compared with SALR but seems as safe and feasible as SALR. ELR may provide improved disease control in some cases of nontuberculous mycobacterial lung disease with multilobar lesions.

Clinical effectiveness of metacognitive training as a transdiagnostic program in routine clinical settings: A prospective, multicenter, single-group study.

AIM: To evaluate the clinical effectiveness of metacognitive training (MCT) as a transdiagnostic program, on a diverse population with mental disorders in routine Japanese day-care settings. METHODS: This study employed a prospective, multicenter, single-group pre-post design. Participants diagnosed with various mental disorders received 10 MCT group sessions. We set transdiagnostic outcomes to assess quality of life, global functioning, cognitive insight, and depressive symptoms. At the end of the MCT, we also evaluated participants' satisfaction with treatment. Assessments were conducted at baseline (Pre), Week 5 (Mid), Week 10 (Post), and Week 14 (follow-up: FU). RESULTS: Thirty-four participants enrolled in the study and received MCT (schizophrenia = 22, non-schizophrenia = 12). Intent-to-treat analyses revealed significant improvements in quality of life/global functioning during the intervention period, and further improvements were observed during the follow-up (all p < .05). The Pre-FU treatment effect sizes for quality of life and global functioning were small (Hedge's g = 0.44 and 0.47, respectively). Significant improvements were also found in depressive symptoms during both the intervention and follow-up periods (all p < .05), but not in cognitive insight. Overall, participants were highly satisfied with the MCT content and format. Scores on almost all outcomes (except for depression) at each assessment point were not significantly different between the schizophrenic and non-schizophrenic sub-groups. CONCLUSIONS: Despite several limitations, mainly due to small sample size and having no control conditions, our results suggest that MCT for a diverse population with mental disorders is a potentially effective approach in improving quality of life/global functioning and other clinical outcomes in routine day-care settings.

Neuropsychological Comparison Between Patients with Social Anxiety and Healthy Controls: Weak Central Coherence and Visual Scanning Deficit.

INTRODUCTION: Although deficits in neuropsychological functioning have been reported in social anxiety disorder (SAD), studies focusing on neuropsychological dysfunction in SAD are limited, and the evidence is still lacking. The purpose of this study was to examine the deficits in neuropsychological functioning in patients with SAD by comparing SAD patients and a healthy control (HC) group. MATERIALS AND METHODS: A total of 72 participants (20 in the SAD group and 52 in the HC group) were assessed with neuropsychological tests, consisting of the Rey Complex Figure Test (RCFT) to measure central coherence and the Trail Making Test A and B (TMT-A; TMT-B) to measure visual scanning and executive functioning. RESULTS: Analysis of covariance with depressive symptoms as a covariate revealed that central coherence (RCFT) and visual scanning (TMT-A) were significantly lower in the SAD group than in the HC group. No difference was found in executive functioning (TMT-B) when the effect of visual scanning was considered. DISCUSSION: Our findings suggest that SAD patients have weak central coherence and deficits in visual scanning compared to healthy controls. The clinical implications of these neuropsychological functioning deficits in SAD patients are discussed.