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.

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.

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.

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.

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.

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.

Selection of Oral Antifungals for Initial Maintenance Therapy in Chronic Pulmonary Aspergillosis: A Longitudinal Analysis.

BACKGROUND: There are limited data for direct comparisons of the efficacy of oral itraconazole (ITCZ) and oral voriconazole (VRCZ) therapy in the treatment of chronic pulmonary aspergillosis (CPA). METHODS: We conducted a retrospective, follow-up, observational study of CPA patients enrolled in 2 previous multicenter trials. RESULTS: Of the 273 CPA patients, 59 and 101 patients started maintenance therapy with oral ITCZ and oral VRCZ, respectively, just after the end of acute intravenous therapy in each trial. At the end of the observation period in this follow-up study (median observation period, 731 days), the percentage of patients who showed improvement was lower in the ITCZ group than in the VRCZ group (18.2% vs 40.0%). However, after including stable patients, the percentages were 50.9% and 52.6%, respectively, in the ITCZ and VRCZ groups, which were not significantly different (P = .652). Multivariable Cox regression analysis showed no significant influence of the choice of initial maintenance treatment (ITCZ or VRCZ) on overall mortality as well as CPA-associated mortality. Multivariable logistic regression showed that oral ITCZ selection for initial maintenance therapy was an independent risk factor for hospital readmission and switching to other antifungal agents (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.3-7.5 and OR, 5.7; 95% CI, 2.0-15.7, respectively). CONCLUSIONS: Oral VRCZ for initial maintenance therapy showed better effectiveness than oral ITCZ for clinical improvement in CPA patients. There was no difference in crude mortality between initial maintenance therapy with VRCZ and ITCZ, especially in elderly CPA patients. CLINICAL TRIALS REGISTRATION: UMIN000007055.

Predictors of response to exposure and response prevention-based cognitive behavioral therapy for obsessive-compulsive disorder.

BACKGROUND: Cognitive behavioral therapy (CBT), which includes exposure and response prevention (ERP), is effective in improving symptoms of obsessive-compulsive disorder (OCD). However, whether poor cognitive functions and autism spectrum disorder (ASD) traits affect the therapeutic response of patients with OCD to ERP-based CBT remains unclear. This study aimed to identify factors predictive of the therapeutic response of Japanese patients with OCD to ERP-based CBT. METHODS: Forty-two Japanese outpatients with OCD were assessed using the Wechsler Adult Intelligence Scale-III (WAIS-III), Yale-Brown Obsessive-Compulsive Scale, Patient Health Questionnaire 9-item scale, and Autism Spectrum Quotient (AQ) at pre- and post-treatment. We used multiple regression analyses to estimate the effect on therapeutic response change. The treatment response change was set as a dependent variable in multiple regression analyses. RESULTS: Multiple regression analyses showed that among independent variables, communication as an AQ sub-scale and Letter Number Sequencing as a WAIS-III sub-test predict the therapeutic response to ERP-based CBT . CONCLUSIONS: Our results suggest that diminished working memory (Letter Number Sequencing), poor communication skill (AQ sub-scale) may undermine responsiveness to ERP-based CBT among patients with OCD. TRIAL REGISTRATION: UMIN, UMIN00024087 . Registered 20 September 2016 - Retrospectively registered (including retrospective data).

Monitoring Vascular Compromise Using Ultrasound After Free Tissue Transfer.

OBJECTIVES: To report the clinical utility of high-resolution ultrasound (US) for monitoring vascular compromise after free tissue transfer. METHODS: Fifty-two tissue transfers in the extremities were included in this study. Blood flow around the anastomotic pedicle and subcutaneous tissue of the grafted flap was monitored with pulsed color and power Doppler US whenever the conventional monitoring method, comprising the bedside assessment of the temperature, capillary refill, and flap color, showed abnormalities until 1 week after reconstruction. RESULTS: All flaps were indicated for US monitoring, with 44 flaps showing Doppler signals in each position, even though conventional flap monitoring showed an abnormality. Forty of the 44 flaps showed no flap failure, whereas the remaining 4 flaps developed partial necrosis. Abnormal US findings were noted in 8 of the 52 flaps. Ultrasound revealed interruption of venous blood flow around the anastomotic pedicle in 6 of 8 flaps. Emergent exploration revealed venous occlusion at the anastomotic pedicle, similar to the US finding. In 2 of the 8 flaps, US showed no blood flow to either the anastomotic pedicle or subcutaneous tissue. Emergent exploration revealed arterial occlusion at the anastomotic pedicle. Seven of the 8 reexplored flaps were salvaged after revision surgery with complete flap survival. Partial flap survival was noted in 1 case, but complete flap failure was avoided. CONCLUSIONS: Ultrasound is a useful adjunct that enables a direct assessment of perfusion in grafted tissues, which may reduce unnecessary exploration when conventional flap monitoring shows an abnormality.

Mobility performance among healthy older adults eligible for long-term care in Japan: a prospective observational study.

BACKGROUND AND AIM: Disability is an important health problem among older individuals, prompting the need for long-term care. Age-related disability is usually associated with mobility; however, little is known about the association between mobility and long-term care. Therefore, this study aimed to clarify the association between the timed up and go (TUG) test measuring mobility and long-term care eligibility. PATIENTS AND METHODS: We analyzed follow-up data of 489 community-dwelling healthy older adults (≥ 65 years) who participated in a prospective observational study. They were divided into certified (59 participants) and uncertified (430 participants) groups based on long-term care eligibility. Anthropometric and physical functioning measures included the TUG test and hand grip strength (HGS), among others. These measures were compared between groups and a multivariate logistic regression analysis evaluated the association between the TUG test times and long-term care eligibility. RESULTS: Participants' minimum follow-up period was 4 years. TUG times were significantly slower (median time: 7.4 vs. 8.3 s, p < 0.001) and HGS and knee-extension strength significantly lower in the certified group than in the uncertified group. The logistic regression analysis showed that TUG times were significantly associated with long-term care eligibility after adjusting for potential covariates. In addition, mediation analysis showed that 53.1% of the association between HGS and long-term care eligibility was mediated through TUG times. CONCLUSION: The TUG test was associated with long-term care eligibility among healthy older adults, implying that the test may be helpful as a predictor for the early determination of dependence in old age.

Endoscopic Hemostasis in Porcine Gastrointestinal Tract Using CO2 Low-Temperature Plasma Jet.

BACKGROUND: Recently, atmospheric low-temperature plasma (LTP) has attracted attention as a novel medical tool that might be useful for achieving hemostasis. However, conventional plasma sources are too big for use with endoscopes, and the efficacy of LTP for achieving hemostasis in cases of gastrointestinal bleeding is difficult to investigate. In this study, to solve the problem, we developed a 3D-printed LTP jet that has a diameter of 2.8 mm and metal body for endoscopic use. The characteristics, hemostasis efficacy, and safety were investigated. MATERIALS AND METHODS: On investigating the basic characteristics of the developed plasma jet, the electron densities, gas temperatures, and reactive species were measured by emission spectroscopy and thermocouple. To evaluate the efficacy of such hemostatic treatment, porcine gastrointestinal bleeding was treated with the device. In addition, to investigate the safety of such treatment, the CO2 LTP-treated tissue was compared with tissue that was treated with clipping-based or argon plasma coagulation-based hemostasis for 5 d, and hematoxylin and eosin staining was used to evaluate tissue damage in the treated regions. RESULTS: The measurement of emission spectroscopy, power, and electron density of various gas plasmas suggested that a high-density (1014 cm-3) LTP of CO2 was generated by the LTP jet, and the gas temperature was 41.5°C at 3 mm from the outlet of the LTP jet. The CO2 LTP achieved hemostasis of oozing blood by 70 ± 20 s. In addition, the CO2 LTP resulted in earlier recovery than clipping-based or argon plasma coagulation-based hemostases, and the treated regions had no damage by the CO2 LTP treatment. CONCLUSIONS: These results indicated that the developed LTP plasma jet has the potential to be used for endoscopic hemostasis.

CRISPR/Cas9 Genome Editing To Demonstrate the Contribution of Cyp51A Gly138Ser to Azole Resistance in Aspergillus fumigatus.

A pan-azole-resistant Aspergillus fumigatus strain with the cyp51A mutations Gly138Ser and Asn248Lys was isolated from a patient receiving long-term voriconazole treatment. PCR fragments containing cyp51A with the mutations were introduced along with the Cas9 protein and single guide RNA into the azole-resistant/susceptible strains. Recombinant strains showed increased susceptibility via the replacement of Ser138 by glycine. Genetic recombination, which has been hampered thus far in clinical isolates, can now be achieved using CRISPR/Cas9 genome editing.

Impact of interventions by an antimicrobial stewardship program team on appropriate antimicrobial therapy in patients with bacteremic urinary tract infection.

BACKGROUND: Inappropriate antimicrobial therapy often leads to poor outcomes. This study aimed to evaluate the impact of an antimicrobial stewardship program (ASP) team on appropriate therapy, in patients with bacteremic urinary tract infection (UTI). PATIENTS AND METHODS: We retrospectively reviewed the interventions by the ASP team in 807 patients with bacteremic UTI. Interventions were divided into 3 groups: group A (conventional report), group B (conventional report and written alert on the chart), and group C (conventional report and oral recommendation with/without written alert). The appropriateness of antimicrobial therapy was assessed at 2 time points, based on blood culture results. RESULTS: The ASP team estimated that 166 and 576 patients received inappropriate antimicrobial therapy based on the results of Gram staining, and final report, respectively. Appropriate therapy after intervention was administered to 53.2% of group A, 63.5% of group B, and 89.3% of group C patients, respectively. Mortality was significantly lower in patients of de-escalation than in those with no antimicrobial changes, without prolonged hospital stay. CONCLUSION: This study provides one plausible benchmark for appropriate antimicrobial therapy by ASP, while observer bias and survivor treatment selection bias exist, and further studies including evaluation for severity are needed.

Joint distraction and early mobilization using a new dynamic external finger fixator for the treatment of fracture-dislocations of the proximal interphalangeal joint.

BACKGROUND: Dynamic external fixation is a useful treatment option for unstable fracture-dislocations of the proximal interphalangeal (PIP) joint, because it simultaneously reduces axial pressure load on the joint surface, maintains congruent joint reduction, and permits early joint motion. However, most current devices are large, hindering finger movement, and unstable. To address these problems, we developed a dynamic external finger fixator, named the Micro Ortho Fixator®. The purpose of this study was to review the results of using the new external finger fixator to treat unstable fracture-dislocations of the PIP joint. MATERIALS AND METHODS: Nine patients who sustained unstable fracture-dislocation injuries of the PIP joint were treated with the Micro Ortho Fixator®. Seven fractures were accompanied by depressed bony fragments at the base of the middle phalanx. All patients were evaluated for pain and range of PIP motion at the final follow-up. Radiographs of the affected fingers were evaluated for PIP congruity and reduction. The mean follow-up duration was 11.1 months (range: 6-33 months). RESULTS: At the final follow-up, pain averaged 0.3 (range: 0-2) on the Numeric Pain Rating Scale, and the total arc of motion at the PIP joint averaged 91.2° (range: 50-110°). All fractures had healed, and the intra-articular step-off improved from 1.9 mm (SD: 1.0) before surgery to 0.2 mm (SD: 0.4) at the final follow-up. The patients who sustained sports injuries returned to competition after an average of 3.5 months (range: 2.5-4 months). CONCLUSION: The external fixator is compact and facilitates range-of-motion (ROM) exercises, has high stability, and achieves good joint congruity and an ROM equivalent to the healthy joint of the patient. STUDY DESIGN/LEVEL OF EVIDENCE: Therapeutic/IV.

Rituximab Restores IFN-γ-STAT1 Function and Ameliorates Disseminated Mycobacterium avium Infection in a Patient with Anti-Interferon-γ Autoantibody.

A 67-year-old Japanese female with back pain and severe cachexia visited our hospital. The diagnosis was disseminated Mycobacterium avium complex infection (dMAC) with multiple bone involvement. Anti-mycobacterial chemotherapy was started, but fever persisted and dislocation of cervical vertebrae has made her bedridden. Because anti-interferon (IFN)-γ autoantibody was positive, four doses of rituximab 375 mg/m2, every 7 day, were administered. Soon after treatment, progression of osteolytic lesions and wasting has stopped. We proved that rituximab has recovered IFN-γ signaling as shown by IFN-γ-induced STAT1 phosphorylation. It can be a promising option for dMAC cases with anti-IFN-γ autoantibody.

[Discussion of Routine Laboratory Data of a Patient Complaining of Back Pain and General Fatigue].

Conventional reversed clinicopathological conference (RCPC) is an educational method to interpret labora- tory data. In this RCPC, physicians and several specialists in laboratory medicine discussed laboratory data of a patient with tuberculous spondylitis who complained of back pain and general fatigue. Then, they and the moderators held a question-and-answer session with an audience in a hall, and they tried to understand the detailed state of the patient. This discussion revealed the usefulness of RCPC to elucidate the clinical state of patient. At the same time, we can understand the limits of laboratory data analysis. [Review].

The effects of the employment of physical therapists and occupational therapists on the gait function of adult day service users after 1 year.

OBJECTIVE: The present study aimed to investigate the effects of the presence or absence of physical therapists (PTs) and occupational therapists (OTs) in an adult day service on the users' gait function, and to generalize the format of an effective service aimed at the preventing the exacerbation of the gait function and at promoting self-reliance in activities and participation. METHODS: The study population included 830 elderly day service users (mean age, 83.7±6.8 years; male, n=252; female, n=578) in Japan. Their normal gait speed was measured at the baseline and at 1 year. The sex, age, level of nursing care, and number of adult day service users were assessed at the baseline. The subjects were divided into 2 groups: (1) those who used services that employed PTs or OTs (the PTOT group) and (2) those who used services that did not employ PTs or OTs (the control group). We performed a univariate analysis to confirm the absence of differences between the groups in terms of all their baseline variables. Next, we performed a repeated measures analysis of variance using the presence or absence of PT or OT and time as factors. We subsequently performed a univariate analysis to examine the difference in the gait speed of the groups, as well as the differences in the gait speed between the groups at the baseline and at 1 year. RESULTS: Although the repeated measures analysis of variance did not show that time had a significant effect on the gait speed, it showed the significant effects of the presence or absence of PTs or OTs as well as the interaction between time and group. Intragroup comparisons showed a significant difference between the gait speed at baseline and that at 1 year in the PTOT group. However, there was also a significant difference in the baseline and 1-year gait speeds of the control group. The intergroup comparisons did not show a significant difference in the gait speed at baseline, but did show a significant difference in the gait speed at 1 year. CONCLUSION: The employment of PTs and OTs in adult day service controlled the exacerbation of the gait function. The gait speed in elderly individuals who require long-term care is associated with the activities of daily living and mortality rates; thus, the results of the present study indicate the need for the employment of rehabilitation specialists in adult day services.