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From the viewpoint of mitigating global warming by SF6 gas, this paper discusses breakdown (BD) characteristics of different electronegative gas mixtures with N2O gas as SF6 gas substitutes for quasi-uniform electric field under lightning impulse voltage applications. Experimental results revealed the positive synergism in breakdown strength of binary N2O/CO2 and ternary N2O/CO2/O2 gas mixtures, respectively. Furthermore, N2 gas as a retardant gas was also mixed with the electronegative gas mixtures in order to reduce the electron energy into the effective levels of electron attachment ability by the electronegative gas mixtures. As the result, ternary N2O/CO2/N2 and quaternary N2O/CO2/O2/N2 gas mixtures could exhibit the significant synergistic effect in breakdown strength. The optimum mixture rate of quaternary N2O/CO2/O2/N2 gas mixtures was consistent with that estimated by assuming the independent contribution of component gases to the improvement of impulse BD characteristics. [ABSTRACT FROM AUTHOR]

Cardiovascular surgery in patients with a retrosternal gastric tube (RGT) remains rare despite improvements in the prognosis of oesophageal cancer. A 75-year old woman with a history of total thoracic oesophagectomy with RGT reconstruction required emergency aortic arch replacement for an acute Stanford type A aortic dissection. We opted for a median sternotomy approach involving complete dissection of the RGT from surrounding tissues and retraction for surgical access to the dissection. Enhanced computed tomography was useful for the diagnosis and planning of the emergency surgery. [ABSTRACT FROM PUBLISHER]

Background: Malignant bowel obstruction affect a patient's quality of life, but, management of MBO is controversial. Case presentation: A 51-year-old woman who had been diagnosed as uterine cervix cancer 2 years ago and had undergone surgery, chemotherapy and radiotherapy, was admitted to our hospital. She was diagnosed as having a recurrence of peritoneal metastasis and bowel obstruction. For her nasal pain, we considered insertion of a postpyloric decompression tube through the gastrostomy instead of via the nasal cavity. After insertion of a percutaneous gastrostomy tube was performed endoscopically, we introduced a postpyloric decompression tube through her gastrostomy. She could be discharged home, and 91 days later, she died in her home under hospice care, as she had wished. Conclusions: Insertion of a postpyloric decompression tube through a gastrostomy might be useful in the management of advanced cancer patients with bowel obstruction [ABSTRACT FROM AUTHOR]

Recently, RccHanTM:WIST (Wistar Hannover) rats were introduced to toxicity studies in Japan. The present study was performed to obtain control data for general toxicological parameters as an aid for interpretation of results in toxicity studies using this strain of rats. Four test groups comprising of 25 male and 25 female RccHanTM:WIST rats were housed for 2, 4, 13 or 26 weeks from 6 weeks of age and observed and examined for clinical observation, body weight, food consumption, urinalysis, hematology, blood chemistry, organ weight, necropsy and/or histopathology. Ophthalmological examination was not conducted in this study, and the data in this report were obtained from an ongoing 104-week background study in RccHanTM:WIST rats. These data were compared with the historical control data of CD(SD) (Sprague-Dawley) and/or F344 (Fischer) rats. The body weights of RccHanTM:WIST rats were lower than those of CD(SD) rats and higher than those of F344 rats. The ophthalmological examination revealed a greater incidence of focal corneal opacity. Histopathology revealed focal mineralization of the cornea and Berlin blue-positive pigmentation in the epididymal interstitium as well as hepatocytes. Other than the above, some minor differences were found in urinalysis, hematology, blood chemistry and organ weights as compared with CD(SD) rats. [ABSTRACT FROM AUTHOR]

Catabolism of branched-chain amino acids (BCAAs) is affected by various physiological conditions and its abnormality is associated with glucose metabolism, heart disease, and neurological dysfunction. The first two steps of the BCAA metabolic pathway are common to the three BCAAs (leucine, isoleucine, and valine). The second step is an irreversible rate-limited reaction catalyzed by branched-chain α-keto acid dehydrogenase (BCKDH), which is bound to a specific kinase, BCKDH kinase (BDK), and inactivated by phosphorylation. Here, we investigated potential new BDK inhibitors and discovered valsartan, an angiotensin II type 1 receptor (AT1R) blocker, as a new BDK inhibitor. BCKDH phosphorylation and the BCKDH-BDK interaction were inhibited by valsartan in vitro. Valsartan administration in rats resulted in increased BCKDH activity by decreasing the dephosphorylated level of BCKDH complex, bound forms of BDK from BCKDH complex as well as decreased plasma BCAA concentrations. Valsartan is a novel BDK inhibitor that competes with ATP, via a different mechanism from allosteric inhibitors. The BDK inhibitor has been shown to preserve cardiac function in pressure overload-induced heart failure mice and to attenuate insulin resistance in obese mice. Our findings suggest that valsartan is a potent seed compound for developing a powerful BDK inhibitor and useful medication for treating heart failure and metabolic diseases with suppressed BCAA catabolism. [Display omitted] • Valsartan was identified as an ATP-competitive inhibitor of BDK from an existing drug library. • Valsartan decreased phosphorylation and disrupted BCKDH-BDK interaction in purified BCKDH 4 complex. • Valsartan administration increased hepatic BCKDH activity as well as decreased plasma BCAA concentration in rats. [ABSTRACT FROM AUTHOR]

The purpose of this systematic review and meta-analysis was to investigate the effects of low-intensity resistance training on knee extension strength with respect to intensity, frequency, duration and training site in community-dwelling older adults. A literature search was conducted for articles published up to December 2018 on PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Physiotherapy Evidence Database (PEDro), OTseeker and Ichushi-Web. Randomized controlled trials involving resistance training with <60 % one repetition maximum (1RM) in community-dwelling older adults aged 60 years and older were eligible. In total, 7 studies involving 275 participants were included in the meta-analysis. The results showed significant improvements in knee extension strength with low-intensity resistance training [standardized mean difference (SMD) 0.62, 95 % confidence interval (CI) 0.32 to 0.91]. In subgroup analyses, significant improvements were observed in the group with intensity at 50–60 % 1RM (0.83, 0.46 to 1.19), but not in the group at 40 % or less 1RM (0.30, 95%CI: −0.08 to 0.68). Concerning frequency, there were significant improvements in knee strength for those receiving training three times (0.90, 0.52 to 1.27) and two times (0.36, 0.03 to 0.69) per week, with a significant difference between the groups (p = 0.04). Low-intensity resistance training should be considered as an effective intervention to improve knee extension strength in community-dwelling older adults. Older adults may show more improvement in knee extension strength if intensity of the training is set at 50–60 % 1RM and frequency of training is three times per week. • It is necessary to develop other effective interventions for safe and sustainable muscle strength training for older adults • Systematic review and meta-analysis to examine the effects of low-intensity resistance training on knee extension strength in older adults. • Older adults may benefit from the low-intensity intervention particularly at more than 50%1RM and from sessions three times per week. [ABSTRACT FROM AUTHOR]

Abstract: The organic/inorganic hybrid particles PSt/P(St-CPEM) θ -g-PDMAEMA/SiO2 were prepared by catalytic hydrolysis and subsequent polycondensation of tetraethoxysilane in the poly[2-(N,N-dimethylamino)ethyl methacrylate] (PDMAEMA) layers grafted on the PSt/P(St-CPEM) θ core/shell heterocoagulates. The micron-sized PSt core and the submicron-sized P(St-CPEM) shell particles bearing ATRP initiating groups were synthesized by dispersion polymerization of styrene (St) and emulsifier-free emulsion polymerization of St with 2-chloropropionyloxyethyl methacrylate (CPEM), respectively. The raspberry-shaped PSt/P(St-CPEM) θ heterocoagulates with a controlled surface coverage (θ =0.51, 0.81) were prepared by hydrophobic coagulation between the core and the shell particles in an aqueous NaCl solution near the T g of P(St-CPEM). Surface modification of heterocoagulates was carried out by ATRP of DMAEMA from the shell particles adsorbed on the core particles. Silica deposition was performed by simply adding tetraethoxysilane to a water/methanol dispersion of PSt/P(St-CPEM) θ -g-PDMAEMA. The SEM and TGA revealed that the resulting PSt/P(St-CPEM) θ -g-PDMAEMA/SiO2 composites maintain a raspberry-like morphology after deposition of silica onto the PDMAEMA layer grafted on heterocoagulates. The micron-sized, raspberry-shaped or the submicron-sized, hole-structured silica hollow particles were obtained selectively by thermal decomposition of the PSt/P(St-CPEM) θ -g-PDMAEMA/SiO2. The oriented particle array was fabricated by dropping anisotropically perforated silica particles onto a glass substrate settled at the bottom of a bottle filled with chloroform. [Copyright &y& Elsevier]

This study aimed to determine the effects of walking-only intervention (walking was the only exercise in which people participated) on physical function, fall-related outcomes, and health-related quality of life in community-dwelling older adults. We conducted a systematic search across five electronic databases, assessing risk of bias using Minds Manual for Guideline Development. Meta-analyses were performed, and pooled standardized mean differences were calculated. Nine studies (a total of 1,309 participants) were included, showing that walking-only interventions improved walking endurance (standardized mean difference: 1.11, 95% confidence interval: [0.08, 2.15]) and health-related quality of life (standardized mean difference: 0.71, 95% confidence interval: [0.18, 1.25]). However, there were no significant improvements in other outcomes. The certainty of the evidence based on the Grading of Recommendations, Assessment, Development, and Evaluation approach for all outcomes was graded as very low, primarily due to significant inconsistency and imprecision. Our results suggest that walking-only intervention can be effective for enhancing walking endurance and health-related quality of life for community-dwelling older adults. Further studies are required to investigate the effects of walking-only intervention. This need stems from the limited number of randomized controlled trials, heterogeneous intervention settings and results, and the very low certainty of the evidence.

Background: The impact of very low baseline levels of low-density lipoprotein cholesterol (LDL-C) on patients with coronary artery disease remains unclear., Method: We enrolled 39,439 patients of the pooled population from the CREDO-Kyoto registries Cohorts 1, 2, and 3. The study population consisted of 33,133 patients who had undergone their first coronary revascularization. We assessed the risk for mortality and cardiovascular events according to quintiles of the baseline LDL-C levels., Results: Patients in the very low LDL-C quintile (<85 mg/dL) had more comorbidities than those in the other quintiles. Lower LDL-C levels were strongly associated with anemia, thrombocytopenia, and end-stage renal disease. The cumulative 4-year incidence of all-cause death increased as LDL-C levels decreased (very low: 19.4 %, low: 14.5 %, intermediate: 11.1 %, high: 10.0 %, and very high: 9.2 %; p < 0.001), which was driven by both the early and late events. After adjusting for baseline characteristics, the adjusted risks of the very low and low LDL-C quintiles relative to the intermediate LDL-C quintile remained significant for all-cause death (very low: HR 1.29, 95 % CI 1.16-1.44, p < 0.001; low: HR 1.15, 95 % CI 1.03-1.29, p = 0.01). The excess adjusted risks of the lowest LDL-C quintile relative to the intermediate LDL-C quintile were significant for clinical outcomes such as cardiovascular death (HR 1.17, 95 % CI 1.01-1.35), non-cardiovascular death (HR 1.35, 95 % CI 1.15-1.60), sudden death (HR 1.44, 95 % CI 1.01-2.06), and heart failure admission (HR 1.11 95 % CI 1.01-1.22), while there was no excess risk for the lowest LDL-C quintile relative to the intermediate LDL-C quintile for myocardial infarction and stroke., Conclusions: Lower baseline LDL-C levels were associated with more comorbidities and a significantly higher risk of death, regardless of cardiovascular or non-cardiovascular causes, in patients who underwent coronary revascularization., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: We investigated the reliability and validity of the 2-min step test (2MST) for assessing the exercise endurance of individuals with stroke and lower-limb musculoskeletal disorders., Participants and Methods: The participants were 39 individuals with stroke and 42 with lower-limb musculoskeletal disorders (mainly hip fractures) from the convalescent rehabilitation wards of four hospitals. The concurrent validity and congruence between the 2MST and the 6-min walk test (6MWT) and construct validity by hypotheses testing, including mobility and lower limb muscle strength, were also confirmed. A subset of participants (stroke-group, n  = 15; musculoskeletal-group, n  = 19) underwent a retest 2MST for our evaluation of relative and absolute reliability using the intraclass correlation coefficient (ICC 1,1 ) and Bland-Altman plot., Results: Both groups showed a moderate correlation between the 2MST and 6MWT ( ρ  = 0.55-0.60), but the congruence was not sufficient. The 6MWT was correlated with mobility in both groups and with muscle strength in the stroke group, whereas the 2MST did not show a significant correlation with mobility. The relative reliability was excellent in both groups (ICC 1,1  > 0.9). In terms of absolute reliability, the width of the limit of agreement was 18.8% for the stroke group and 15.4% for the musculoskeletal group, relative to their respective sample means of 2MST. A fixed bias was identified in the stroke group, in which step counts increased by 6.5 steps upon retesting., Discussion: Our analyses revealed that the 2MST is a valid and reliable tool for assessing the exercise endurance of individuals with stroke or lower-limb musculoskeletal disorders. However, it is necessary to validate the absolute reliability observed herein by using a larger sample size. In addition, when assessing the exercise endurance of individuals with stroke, it may be necessary to consider the potential bias of an increased step count during retesting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Ishigaki, Kubo, Yoshida, Shimizu and Ogawa.)

Background: Evidence-based medicine education has not focused on how clinicians involve patients in decision-making. Although shared decision-making (SDM) has been investigated to address this issue, there are insufficient data on SDM in physiotherapy. This study aimed to clarify the issues concerning patient involvement in Japan, and to examine whether SDM is related to perceptions of patient involvement in decision-making., Methods: The study participants were recruited from among acute and sub-acute inpatients and community residents receiving physiotherapy outpatient care, day care, and/or home rehabilitation. The Control Preference Scale (CPS) was used to measure the patients' involvement in decision-making. The nine-item Shared Decision-Making Questionnaire (SDM-Q-9) was used to measure SDM. In analysis I, we calculated the weighted kappa coefficient to examine the congruence in the CPS between the patients' actual and preferred roles. In analysis II, we conducted a logistic regression analysis using two models to examine the factors of patient involvement., Results: Analysis I included 277 patients. The patients' actual roles were as follows: most active (4.0%), active (10.8%), collaborative (24.6%), passive (35.0%), and most passive (25.6%). Their preferred roles were: most active (3.3%), active (18.4%), collaborative (39.4%), passive (24.5%), and most passive (14.4%). The congruence between actual and preferred roles by the kappa coefficient was 0.38. Analysis II included 218 patients. The factors for patient involvement were the clinical environment, the patient's preferred role, and the SDM-Q-9 score., Conclusions: The patients in Japan indicated a low level of decision-making involvement in physiotherapy. The patients wanted more active involvement than that required in the actual decision-making methods. The physiotherapist's practice of SDM was revealed as one of the factors related to perceptions of patient involvement in decision-making. Our results demonstrated the importance of using SDM for patient involvement in physiotherapy., (© 2023. The Author(s).)

Objectives: This study aimed to systematically analyze the efficacy of therapeutic exercise on activities of daily living (ADL) and cognitive function among older residents in long-term care facilities., Data Sources: PubMed, Cochrane Central of Register Trials, Physiotherapy Evidence Database, OTseeker, and Ichushi-Web were searched from inception until December 2018., Study Selection: Databases were searched to identify randomized controlled trials (RCTs) of therapeutic exercise for long-term care facility residents aged 60 years and older, focusing on ADL and cognitive function as outcomes., Data Extraction: Two independent reviewers extracted the key information from each eligible study. Two reviewers independently screened and assessed all studies for eligibility, extracting information on study participants, details of interventions, outcome characteristics, and significant outcomes. Any discrepancies were resolved by a third reviewer., Data Synthesis: A total of 11 RCTs with 1280 participants were eligible for analyses. Therapeutic exercise had a significant benefit on ADL (standard mean difference [SMD]=0. 22, 95% confidence interval [CI]: 0.02, 0.42, P=.03). Subgroup analyses indicated that interventions conducted ≥3 days per week [SMD=0.42, 95% CI 0.02, 0.82, P=.04] had a significant benefit on ADL. For cognitive function, group exercise and ≥3 days/week of intervention had a significant benefit (group exercise: mean difference [MD]=3.36, 95% CI 0.91, 5.80, P=.007; ≥3 days/week of intervention: MD=2.28, 95% CI 0.07, 4.49, P=.04)., Conclusions: Therapeutic exercise conducted 3 or more days per week may be effective for improving ADL and cognitive function among older residents in long-term care facilities. This meta-analysis suggested that group exercise for cognitive functions was effective. However, the effective method of intervention delivery for ADL was unclear., (Copyright © 2022 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

For unknow reasons, the melanocyte stem cell (McSC) system fails earlier than other adult stem cell populations 1 , which leads to hair greying in most humans and mice 2,3 . Current dogma states that McSCs are reserved in an undifferentiated state in the hair follicle niche, physically segregated from differentiated progeny that migrate away following cues of regenerative stimuli 4-8 . Here we show that most McSCs toggle between transit-amplifying and stem cell states for both self-renewal and generation of mature progeny, a mechanism fundamentally distinct from those of other self-renewing systems. Live imaging and single-cell RNA sequencing revealed that McSCs are mobile, translocating between hair follicle stem cell and transit-amplifying compartments where they reversibly enter distinct differentiation states governed by local microenvironmental cues (for example, WNT). Long-term lineage tracing demonstrated that the McSC system is maintained by reverted McSCs rather than by reserved stem cells inherently exempt from reversible changes. During ageing, there is accumulation of stranded McSCs that do not contribute to the regeneration of melanocyte progeny. These results identify a new model whereby dedifferentiation is integral to homeostatic stem cell maintenance and suggest that modulating McSC mobility may represent a new approach for the prevention of hair greying., (© 2023. The Author(s).)

In this study, we report on a computational fluid dynamics (CFD) simulation of the chemical vapor deposition reactor of silicon carbide (SiC) in the methyltrichlorosilane (MTS, CH 3 SiCl 3 )/H 2 system. The formation of SiC thin film is controlled by various process parameters, such as temperature and pressure. In this study, we propose a reaction mechanism of MTS decomposition to SiC growth on a substrate surface for CVD reactors in the CH 3 SiCl 3 (MTS)/H 2 system. The reaction mechanism has two gas-phase pyrolysis reactions and one SiC film formation reaction. However, we individually build and validate MTS decomposition and SiC growth models to reduce uncertainty. An in-house version of reactingFoam, a reactive flow solver within OpenFOAM v2006, was used as the simulation tool. Our model accurately reproduced MTS decomposition for T  = 1100-1350 K and [H 2 ]/[MTS] = 2.65-14 at p  = 101,325 Pa. Then, the MTS decomposition model was coupled with the SiC growth model, and the coupled model was applied to the SiC deposition data. The model could reproduce multiple datasets through validation studies., (© 2023 The Authors.)

We report 2 cases of transfusion-free treatment for H3 grade of simultaneous liver metastases of the colon which were treated with the chemotherapy followed by R0 liver resection. Case 1 was a 67-year-old woman bearing ascending colon cancer and a metastatic mass occupying the left lobe of the liver with 160 mm in diameter. Laparoscopic ileocecal resection and 30-day left hepatectomy were performed after the 7 courses of FOLFOX plus bevacizumab(BEV). Case 2 was a 72- year-old woman bearing transverse colon cancer with more than 10 foci of liver metastases ranging from 21 mm to 100 mm in diameter. After the transverse colon resection and 12 months of chemotherapy from FOLFOX plus BEV to FOLFIRI plus panitumumab, partial liver resection was performed for each of size-reduced foci. In both patients who declined blood transfusion, optimization of red cells and autologous transfusion with hemodilution contributed to the safe liver resection with no postoperative complications.

Melanogenesis is a major part of the environmental responses and tissue development of the integumentary system. The balance between reduction and oxidation (redox) governs pigmentary responses, for which coordination among epidermal resident cells is indispensable. Here, we review the current understanding of melanocyte biology with a particular focus on the "master regulator" of oxidative stress responses (i.e., the Kelch-like erythroid cell-derived protein with cap'n'collar homology-associated protein 1-nuclear factor erythroid-2-related factor 2 system) and the autoimmune pigment disorder vitiligo. Our investigation revealed that the former is essential in pigmentogenesis, whereas the latter results from unbalanced redox homeostasis and/or defective intercellular communication in the interfollicular epidermis (IFE). Finally, we propose a model in which keratinocytes provide a "niche" for differentiated melanocytes and may "imprint" IFE pigmentation., Competing Interests: The authors declare no conflict of interest.

Purpose: Exercise motivation (EM) is related to individual capabilities and social support. However, in support facilities for people with disabilities, it is susceptible to a lack of social support. In this study, we classified EM into Autonomous Motivation (AM) and controlled motivation (CM) and then examined the influence of social support., Method: Thirty-three residents from a support facility for people with disabilities in Japan participated in this study. We conducted a hierarchical multiple regression analysis in which age, gender and time since admission were entered in Step 1, mobility and self-efficacy as individual capabilities in Step 2, and family support, facility support and peer support as social support in Step 3., Result: A significant increase in variance from Step 2 to Step 3 was found for both AM (Δ R 2  = 0.504, Δ F  = 12.18, p  < .001) and CM (Δ R 2  = 0.269, Δ F  = 3.491, p  = .031). The results also showed that AM was higher among those with high family and facility support, and CM was higher among those with low family and high peer support., Conclusions: Social support was a more significant predictor of EM among participants than individual capabilities.KEY MESSAGESAmong residents of support facilities for people with disabilities, assessing not only individual capabilities but also social support status can lead to better understandings of exercise motivation (EM).To enhance facility residents' autonomous motivation (AM), it is necessary to intervene after evaluating family and facility support.When family support is not readily available among facility residents, efforts should be made to encourage residents to interact with each other to increase peer support.

We report a case of ruptured abdominal aortic aneurysm complicated with occlusion of bilateral common iliac arteries. A 68-year-old man complained of sudden onset of lower abdominal and back pain. A contrast-enhanced computed tomography showed ruptured abdominal aortic aneurysm of about 80 mm in diameter and a giant retroperitoneal hematoma, as well as occlusion of both common iliac arteries. We performed Y-grafting, concomitant with thrombectomy of both iliac arteries from inside the aneurysm. Postoperative course was uneventful without ischemic findings of the legs and the patient was discharged on the 17 th postoperative day.

Aims: There is a scarcity of studies comparing percutaneous coronary intervention (PCI) using new-generation drug-eluting stents (DES) with coronary artery bypass grafting (CABG) in patients with multi-vessel coronary artery disease., Methods and Results: The CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients who underwent first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013. The current study population consisted of 2464 patients who underwent multi-vessel coronary revascularization including revascularization of left anterior descending coronary artery (LAD) either with PCI using new-generation DES (N = 1565), or with CABG (N = 899). Patients in the PCI group were older and more often had severe frailty, but had less complex coronary anatomy, and less complete revascularization than those in the CABG group. Cumulative 5-year incidence of a composite of all-cause death, myocardial infarction or stroke was not significantly different between the 2 groups (25.0% versus 21.5%, P = 0.15). However, after adjusting confounders, the excess risk of PCI relative to CABG turned to be significant for the composite endpoint (HR 1.27, 95%CI 1.04-1.55, P = 0.02). PCI as compared with CABG was associated with comparable adjusted risk for all-cause death (HR 1.22, 95%CI 0.96-1.55, P = 0.11), and stroke (HR 1.17, 95%CI 0.79-1.73, P = 0.44), but with excess adjusted risk for myocardial infarction (HR 1.58, 95%CI 1.05-2.39, P = 0.03), and any coronary revascularization (HR 2.66, 95%CI 2.06-3.43, P<0.0001)., Conclusions: In this observational study, PCI with new-generation DES as compared with CABG was associated with excess long-term risk for major cardiovascular events in patients who underwent multi-vessel coronary revascularization including LAD., Competing Interests: The authors have declared that no competing interests exist.

The Kelch-like erythroid cell-derived protein with cap'n'collar homology-associated protein 1 (KEAP1)-nuclear factor erythroid-2-related factor 2 (NRF2) system, a thiol-based sensor-effector apparatus, exerts antioxidative and anti-inflammatory effects and maintains skin homeostasis. Thus, NRF2 activation appears to be a promising treatment option for various skin diseases. However, NRF2-mediated defense responses may deteriorate skin inflammation in a context-dependent manner. Atopic dermatitis (AD) and psoriasis are two common chronic inflammatory skin diseases caused by a defective skin barrier, dysregulated immune responses, genetic predispositions, and environmental factors. This review focuses on the role of the KEAP1-NRF2 system in the pathophysiology of AD and psoriasis and the therapeutic approaches that utilize this system.

[Purpose] This study aimed to investigate the influence of the evidence practice gap on physiotherapist and occupational therapists through shared decision making using the clinical practice guidelines. [Participants and Methods] A randomized controlled trial was used. The participants included 126 therapists from three institutions. The inclusion criteria was permanent employment in these institutions. Participants' characteristics were masked from the allocator, evaluator, and analyzer. For the intervention group, a workshop on shared decision making was conducted using clinical practice guidelines. Two control groups were set. One group received a lecture on the knowledge of clinical practice guidelines, and the other group received a lecture on the knowledge of shared decision making. The primary outcomes were "education, attitudes and beliefs, and interest and perceived role in evidence-based practice" scale. [Results] The primary outcomes showed a significant difference between the clinical practice guidelines with shared decision making group and the clinical practice guidelines group (mean ± standard deviation, pre/post; clinical practice guidelines with shared decision making group, 2.4 ± 0.9/4.4 ± 1.7; clinical practice guidelines group, 3.0 ± 1.5/3.5 ± 2.0; shared decision making group, 2.6 ± 1.2/ 3.3 ± 1.8). [Conclusion] Shared decision making education using the clinical practice guidelines improves evidence-based practice of self-efficacy in physiotherapists and occupational therapists., (2022©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Background: Diabetes is a well-known risk factor for adverse outcomes after coronary revascularization., Objectives: This study sought to determine high-risk subgroups in whom the excess risks of diabetes relative to nondiabetes are particularly prominent and thus may benefit from more aggressive interventions., Methods: The study population consisted of 39,427 patients (diabetes: n = 15,561; nondiabetes: n = 23,866) who underwent first percutaneous coronary intervention (n = 33,144) or coronary artery bypass graft (n = 6,283) in the pooled CREDO-Kyoto PCI/CABG (Coronary Revascularization Demonstrating Outcome Study in Kyoto Percutaneous Coronary Intervention/Coronary Artery Bypass Graft) registry. The primary outcome measure was major adverse cardiovascular and cerebral endpoints (MACCE), which was defined as a composite of all-cause death, myocardial infarction, and stroke., Results: With median follow-up of 5.6 years, diabetes was associated with significantly higher adjusted risks for MACCE. The excess adjusted risks of diabetes relative to nondiabetes for MACCE increased with younger age (≤64 years: adjusted HR: 1.30; 95% CI: 1.19-1.41; P  < 0.001; 64-73 years: adjusted HR: 1.24; 95% CI: 1.16-1.33; P  < 0.001; >73 years: adjusted HR: 1.17; 95% CI: 1.10-1.23; P  < 0.001; P interaction  < 0.001), mainly driven by greater excess adjusted mortality risk of diabetes relative to nondiabetes in younger tertile. No significant interaction was observed between adjusted risk of diabetes relative to nondiabetes for MACCE and other subgroups such as sex, mode of revascularization, and clinical presentation of acute myocardial infarction., Conclusions: The excess risk of diabetes relative to nondiabetes for MACCE was profound in the younger population. This observation suggests more aggressive interventions for secondary prevention in patients with diabetes might be particularly relevant in younger patients., Competing Interests: This study was supported by an educational grant from the Research Institute for Production Development (Kyoto, Japan). Dr Yamaji has received a research grant from Abbott Vascular. Dr Shiomi has received honoraria from Abbott Vascular and Boston Scientific. Dr Morimoto has received lecturer's fees from Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Kyocera, Novartis, and Toray; manuscript fees from Bristol-Myers Squibb and Kowa; and has served on the Advisory Board of Sanofi. Dr Ehara has received honoraria from Abbott Vascular, Bayer, Boston Scientific, Medtronic, and Terumo. Dr Furukawa has received honoraria from Bayer, Kowa, and Sanofi. Dr Nakagawa has received research grants from Abbott Vascular and Boston Scientific; and honoraria from Abbott Vascular, Bayer, and Boston Scientific. Dr Kimura has received a research grant from Abbott Vascular; and honoraria from Astellas, AstraZeneca, Bayer, Boston Scientific, Kowa, and Sanofi. All the other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

Background: The clinical significance of concomitant mitral regurgitation (MR) has not been well addressed in patients with severe aortic stenosis (AS).Methods and Results:We analyzed 3,815 patients from a retrospective multicenter registry of severe AS in Japan (CURRENT AS registry). We compared the clinical outcomes between patients with moderate/severe MR and with none/mild MR according to the initial treatment strategy (initial aortic valve replacement [AVR] or conservative strategy). The primary outcome measure was a composite of aortic valve-related death or heart failure hospitalization. At baseline, moderate/severe MR was present in 227/1,197 (19%) patients with initial AVR strategy and in 536/2,618 (20%) patients with a conservative strategy. The crude cumulative 5-year incidence of the primary outcome measure was significantly higher in patients with moderate/severe MR than in those with none/mild MR, regardless of the initial treatment strategy (25.2% vs. 14.4%, P<0.001 in the initial AVR strategy, and 63.3% vs. 40.7%, P<0.001 in the conservative strategy). After adjusting confounders, moderate/severe MR was not independently associated with higher risk for the primary outcome measure in the initial AVR strategy (hazard ratio [HR] 1.11, 95% confidence interval [CI] 0.67-1.83, P=0.69), and in the conservative strategy (HR 1.13, 95% CI 0.93-1.37, P=0.22)., Conclusions: Concomitant moderate/severe MR was not independently associated with higher risk for the primary outcome measure regardless of the initial treatment strategy.

Competing Interests: There are no financial or other issues that might lead to conflict of interest.

The treatment of coronary artery disease has substantially changed over the past two decades. However, it is unknown whether and how much these changes have contributed to the improvement of long-term outcomes after coronary revascularization. We assessed trends in the demographics, practice patterns and long-term outcomes in 24,951 patients who underwent their first percutaneous coronary intervention (PCI) (n = 20,106), or isolated coronary artery bypass grafting (CABG) (n = 4,845) using the data in a series of the CREDO-Kyoto PCI/CABG Registries (Cohort-1 [2000 to 2002]: n = 7,435, Cohort-2 [2005 to 2007]: n = 8,435, and Cohort-3 [2011 to 2013]: n = 9,081). From Cohort-1 to Cohort-3, the patients got progressively older across subsequent cohorts (67.0 ± 10.0, 68.4 ± 9.9, and 69.8 ± 10.2 years, p trend < 0.001). There was increased use of PCI over CABG (73.5%, 81.9%, and 85.2%, p trend < 0.001) and increased prevalence of evidence-based medications use over time. The cumulative 3-year incidence of all-cause death was similar across the 3 cohorts (9.0%, 9.0%, and 9.3%, p = 0.74), while cardiovascular death decreased over time (5.7%, 5.1%, and 4.8%, p = 0.03). The adjusted risk for all-cause death and for cardiovascular death progressively decreased from Cohort-1 to Cohort-2 (HR:0.89, 95%CI:0.80 to 0.99, p = 0.03, and HR:0.80, 95%CI:0.70 to 0.92, p = 0.002, respectively), and from Cohort-2 to Cohort-3 (HR:0.86, 95%CI:0.78 to 0.95, p = 0.004, and HR:0.77, 95%CI:0.67-0.89, p < 0.001, respectively). The risks for stroke and repeated coronary revascularization also improved over time. In conclusions, we found a progressive and substantial reduction of adjusted risk for all-cause death, cardiovascular death, stroke, and repeated coronary revascularization over the past two decades in Japan., (Copyright © 2021 Elsevier Inc. All rights reserved.)

There is a scarcity of data comparing long-term clinical outcomes between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with three-vessel coronary artery disease (3VD) in the new-generation drug-eluting stents era. CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients who had undergone first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013. We identified 2525 patients with 3VD (PCI: n = 1747 [69%], and CABG: n = 778 [31%]). The primary outcome measure was all-cause death. Median follow-up duration was 5.7 (interquartile range: 4.4 to 6.6) years. The cumulative 5-year incidence of all-cause death was significantly higher in the PCI group than in the CABG group (19.8% vs 13.2%, log-rank p = 0.001). After adjusting confounders, the excess risk of PCI relative to CABG for all-cause death remained significant (HR, 1.45; 95% CI, 1.14 to 1.86; p = 0.003), which was mainly driven by the excess risk for non-cardiovascular death (HR, 1.88; 95% CI, 1.30 to 2.79; p = 0.001), while there was no excess risk for cardiovascular death between PCI and CABG (HR, 1.19; 95% CI, 0.87 to 1.64; p = 0.29). There was significant excess risk of PCI relative to CABG for myocardial infarction (HR, 1.77; 95% CI, 1.19 to 2.69; p = 0.006), whereas there was no excess risk of PCI relative to CABG for stroke (HR, 1.24; 95% CI, 0.83 to 1.88; p = 0.30). In conclusion, in the present study population reflecting real-world clinical practice in Japan, PCI compared with CABG was associated with significantly higher risk for all-cause death, while there was no excess risk for cardiovascular death between PCI and CABG., Competing Interests: Declaration of Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this study., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A 54-year old man suffering from back pain was diagnosed with Stanford type A aortic dissection in our emergency unit. During the preparation of the operating room, he developed coronary ischemia with chest pain and depressed blood pressure accompanied with abnormal electro- and echocardiography findings. He was transported to the catheter laboratory where stent placement into the left main coronary artery was successfully performed. Thereafter, he underwent total arch replacement, during which the stent was removed intentionally without performing coronary artery bypass graft. His postoperative course was uneventful and he is doing well without any ischemic event for 2 years after the surgery.

Solid-state NMR is a powerful analytical technique to determine the composite structure of Bombyx mori silk fibroin (SF). In our previous paper, we proposed a lamellar structure for Ala-Gly copolypeptides as a model of the crystalline fraction in Silk II. In this paper, the structure and dynamics of the crystalline fraction and of a better mimic of the crystalline fraction, (Ala-Gly-Ser-Gly-Ala-Gly) n (n = 2-5, 8), and 13 C selectively labeled [3- 13 C]Ala-(AGSGAG) 5 in Silk II forms, were studied using structural and dynamical analyses of the Ala Cβ peaks in 13 C cross polarization/ magic angle spinning NMR and 13 C solid-state spin-lattice relaxation time (T 1 ) measurements, respectively. Like Ala-Gly copolypeptides, these materials have lamellar structures with two kinds of Ala residues in β-sheet, A and B, plus one distorted β-turn, t, formed by repetitive folding using β-turns every eighth amino acid in an antipolar arrangement. However, because of the presence of Ser residues at every sixth residue in (AGSGAG) n , the T 1 values and mobilities of B decreased significantly. We conclude that the Ser hydroxyls hydrogen bond to adjacent lamellar layers and fix them together in a similar way to Velcro®., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: The stratum corneum protects against the entry of pathogens, allergens, and irritants while preventing dehydration. The Kelch-like erythroid cell-derived protein with cap-n-collar homology-associated protein 1 (KEAP1)/NF-E2-related factor 2 (NRF2) system maintains skin barrier homeostasis. Aggregated evidence suggests that NRF2-mediated antioxidative response is hardwired into the stratified squamous epithelia. Honey and chamomile have long been regarded as natural antioxidants. Nonetheless, it is still unclear whether they activate the KEAP1/NRF2 system in the epidermis and could promote epidermal barrier recovery., Methods: To address the abovementioned issue, we explored the antioxidative property of honey/chamomile extract by using non-cell-based KEAP1-inhibition assay and cultured human epidermal keratinocytes., Results: Herein we report that the extract inhibited KEAP1-NRF2 interaction and induced keratinocyte production of antioxidant small proline-rich protein., Conclusion: Our results may offer an opportunity to develop cosmetic products that boost NRF2-mediated antioxidative/antiaging, epidermis-intrinsic bio-responses., Competing Interests: This research was supported in part by the following JSPS KAKENHI Grant, Grant-in-Aid for Research Activity Start-up (16H06663 to YI), and Early-Career Scientists (18K16018 to YI). The authors state they have no conflicts of interest for this work., (© 2020 Ogawa et al.)

Psoriasis is an autoinflammatory/autoimmune skin disease and the epitome of an exaggerated primary inflammatory response in the surface barrier tissue. Despite the efficacy of dimethyl fumarate, an electrophilic drug for psoriasis management, there is a paucity of mechanistic evidence in vivo. In response to electrophiles, the Kelch-like erythroid cell-derived protein with cap-n-collar homology-associated protein 1/nuclear factor erythroid 2-related factor 2 (NRF2) system mediates a myriad of cytoprotective mechanisms, including the regulation of excessive inflammatory response and epidermal differentiation. Because the psoriasiform tissue reaction comprises neutrophil infiltration and parakeratotic scaling, it is hypothesized that Nrf2 not only regulates inflammatory responses but also maintains epidermal differentiation, a hallmark of epidermal homeostasis. By using the imiquimod-induced cutaneous inflammation model, an exaggerated inflammatory response and impaired epidermal differentiation in Nrf2 -/- mice was detected. Dimethyl fumarate treatment in Nrf2 +/+ mice attenuated a psoriasiform tissue reaction and rescued epidermal differentiation, which was not observed in Nrf2 -/- mice. In accordance with the fact that psoriasis plaques form well-demarcated parakeratotic lesions in association with the psoriasiform tissue reaction, the lesional skin showed reduced expression levels of NRF2 and its downstream target genes compared with nonlesional skin. In conclusion, Nrf2 attenuates the psoriasiform tissue reaction and underscores the mechanistic legitimacy of the electrophile-based approach for the management of psoriasis., (Copyright © 2020 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Aims: Tricuspid regurgitation (TR) has been reported to be associated with worse survival in various heart diseases, but there are few data in aortic stenosis (AS)., Methods and Results: In the Contemporary Outcomes after Surgery and Medical Treatment in Patients with Severe Aortic Stenosis (CURRENT AS) Registry enrolling 3815 consecutive patients with severe AS, there were 628 patients with moderate or severe TR (TR group) and 3187 patients with no or mild TR (no TR group). The study patients were subdivided into the initial aortic valve replacement (AVR) stratum (n = 1197) and the conservative stratum (n = 2618) according to treatment strategy. The primary outcome measure was a composite of aortic valve-related death or hospitalization due to heart failure. The 5-year freedom rate from the primary outcome measure was significantly lower in the TR group than in the no TR group (49.1% vs. 67.3%, P < 0.001). Even after adjusting for confounders, the excess risk of TR relative to no TR for the primary outcome measure remained significant [hazard ratio (HR): 1.25, 95% confidence interval (CI): 1.06-1.48; P = 0.008]. The trend for the excess adjusted risk in the TR group was consistent in the initial AVR and the conservative strata (HR 1.55, 95% CI: 0.97-2.48; P = 0.07; HR 1.22, 95% CI: 1.02-1.46; P = 0.03, respectively). In the initial AVR stratum, the 5-year freedom rate from the primary outcome measure was not different between the two groups with (n = 56) or without (n = 91) concomitant tricuspid annuloplasty (61.5% vs. 72.1%, P = 0.48)., Conclusion: The presence of clinically significant TR concomitant with severe AS is associated with a poor long-term outcome, regardless of the initial treatment strategy., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Background: There is no large-scale study comparing postoperative mortality after aortic valve replacement (AVR) for asymptomatic severe aortic stenosis (AS) between initial treatment with AVR vs. eventual AVR after conservative management. Methods and Results: We analyzed data from a multicenter registry enrolling 3,815 consecutive patients with severe AS. Of 1,808 asymptomatic patients, 286 patients initially underwent AVR (initial AVR group), and 377 patients were initially managed conservatively and eventually underwent AVR (AVR after watchful waiting group). Mortality after AVR was compared between the 2 groups. Subgroup analysis according to peak aortic jet velocity (Vmax) at diagnosis was also conducted. There was no significant difference between the 2 groups in 5-year overall survival (OS; 86.0% vs. 84.1%, P=0.34) or cardiovascular death-free survival (DFS; 91.3% vs. 91.1%, P=0.61), but on subgroup analysis of patients with Vmax ≥4.5 m/s at diagnosis, the initial AVR group was superior to the AVR after watchful waiting group in both 5-year OS (88.4% vs. 70.6%, P=0.003) and cardiovascular DFS (91.9% vs. 81.7%, P=0.023)., Conclusions: Asymptomatic severe AS patients who underwent AVR after watchful waiting had a postoperative survival rate similar to those who initially underwent AVR. In a subgroup of patients with Vmax ≥4.5 m/s at diagnosis, however, the AVR after watchful waiting group had worse postoperative survival rate than the initial AVR group.