Cryo-EM structures of RNA polymerase II-nucleosome complexes rewrapping transcribed DNA.

RNA polymerase II (RNAPII) transcribes DNA wrapped in the nucleosome by stepwise pausing, especially at nucleosomal superhelical locations -5 and -1 [SHL(-5) and SHL(-1), respectively]. In the present study, we performed cryo-electron microscopy analyses of RNAPII-nucleosome complexes paused at a major nucleosomal pausing site, SHL(-1). We determined two previously undetected structures, in which the transcribed DNA behind RNAPII is sharply kinked at the RNAPII exit tunnel and rewrapped around the nucleosomal histones in front of RNAPII by DNA looping. This DNA kink shifts the DNA orientation toward the nucleosome, and the transcribed DNA region interacts with basic amino acid residues of histones H2A, H2B, and H3 exposed by the RNAPII-mediated nucleosomal DNA peeling. The DNA loop structure was not observed in the presence of the transcription elongation factors Spt4/5 and Elf1. These RNAPII-nucleosome structures provide important information for understanding the functional relevance of DNA looping during transcription elongation in the nucleosome.

Myc upregulates Ggct, γ-glutamylcyclotransferase to promote development of p53-deficient osteosarcoma.

Osteosarcoma (OS) in humans is characterized by alterations in the TP53 gene. In mice, loss of p53 triggers OS development, for which c-Myc (Myc) oncogenicity is indispensable. However, little is known about which genes are targeted by Myc to promote tumorigenesis. Here, we examined the role of γ-glutamylcyclotransferase (Ggct) which is a component enzyme of the γ-glutamyl cycle essential for glutathione homeostasis, in human and mouse OS development. We found that GGCT is a poor prognostic factor for human OS, and that deletion of Ggct suppresses p53-deficient osteosarcomagenesis in mice. Myc upregulates Ggct directly by binding to the Ggct promoter, and deletion of a Myc binding site therein by genome editing attenuated the tumorigenic potential of p53-deficient OS cells. Taken together, these results show a rationale that GGCT is widely upregulated in cancer cells and solidify its suitability as a target for anticancer drugs.

Changes in long-term care insurance revenue among service providers during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has impacted peoples' health-related behaviors, especially those of older adults, who have restricted their activities in order to avoid contact with others. Moreover, the pandemic has caused concerns in long-term care insurance (LTCI) providers regarding management and financial issues. This study aimed to examine the changes in revenues among LTCI service providers in Japan during the pandemic and analyze its impact on different types of services. METHODS: In this study, we used anonymized data from "Kaipoke," a management support platform for older adult care operators provided by SMS Co., Ltd. Kaipoke provides management support services to more than 27,400 care service offices nationwide and has been introduced in many home-care support offices. The data used in this study were extracted from care plans created by care managers on the Kaipoke platform. To examine the impact of the pandemic, an interrupted time-series analysis was conducted in which the date of the beginning of the pandemic was set as the prior independent variable. RESULTS: The participating providers were care management providers (n = 5,767), home-visit care providers (n = 3,506), home-visit nursing providers (n = 971), and adult day care providers (n = 4,650). The results revealed that LTCI revenues decreased significantly for care management providers, home-visit nursing providers, and adult day care providers after the COVID-19 pandemic began. The largest decrease was an average base of USD - 1668.8 in adult day care. CONCLUSION: The decrease in revenue among adult day care providers was particularly concerning in terms of the sustainability of their business. This decrease in revenue may have made it difficult to retain personnel, and staff may have needed to be laid off as a result. Although this study has limitations, it may provide useful suggestions for countermeasures in such scenarios, in addition to support conducted measures.

High Cathode Loading and Low-Temperature Operating Garnet-Based All-Solid-State Lithium Batteries - Material/Process/Architecture Optimization and Understanding of Cell Failure.

All-solid-state lithium batteries (ASSLBs) are prepared using garnet-type solid electrolytes by quick liquid phase sintering (Q-LPS) without applying high pressure during the sintering. The cathode layers are quickly sintered with a heating rate of 50-100 K min-1 and a dwell time of 10 min. The battery performance is dramatically improved by simultaneously optimizing materials, processes, and architectures, and the initial discharge capacity of the cell with a LiCoO2 -loading of 8.1 mg reaches 1 mAh cm-2 and 130 mAh g-1 at 25 °C. The all-solid-state cell exhibits capacity at a reduced temperature (10 °C) or a relatively high rate (0.1 C) compared to the previous reports. The Q-LPS would be suitable for large-scale manufacturing of ASSLBs. The multiphysics analyses indicate that the internal stress reaches 1 GPa during charge/discharge, which would induce several mechanical failures of the cells: broken electron networks, broken ion networks, separation of interfaces, and delamination of layers. The experimental results also support these failures.

The Effect of Home Care Support Clinics on Hospital Readmission in Heart Failure Patients in Japan.

BACKGROUND: Heart failure is common and is associated with high rates of hospitalization. Home care support clinics/hospitals (HCSCs) and enhanced HCSCs were introduced in Japan in 2006 and 2012, respectively. OBJECTIVE: This study aimed to examine the effect of post-discharge care by conventional or enhanced HCSCs on readmission, compared with general clinics. DESIGN: Retrospective cohort study using the Japanese nationwide health insurance claims database. PARTICIPANTS: Participants were ≥65 years of age, admitted for heart failure and discharged between July 2014 and August 2015 and received a home visit within a month following the discharge (n=12,393). MAIN MEASURES: The exposure was the type of medical facility that provides post-discharge home healthcare: general clinics, conventional HCSCs, and enhanced HCSCs. The primary outcome was all-cause readmission for 6 months after the first visit; the incidence of emergency house calls was a secondary outcome. We used a competing risk regression using the Fine and Gray method, in which death was regarded as a competing event. KEY RESULTS: At 6 months, readmissions were lower in conventional (38%) or enhanced HCSCs (38%) than general clinics (43%). The adjusted subdistribution hazard ratio (sHR) of readmission was 0.87 (95% CI: 0.78-0.96) for conventional and 0.86 (0.78-0.96) for enhanced HCSCs. Emergency house calls increased with conventional (sHR: 1.77, 95% CI:1.57-2.00) and enhanced HCSCs (sHR: 1.93, 95% CI: 1.71-2.17). CONCLUSIONS: Older Japanese patients with heart failure receiving post-discharge home healthcare by conventional or enhanced HCSCs had lower readmission rates, possibly due to compensation with more emergency house calls. Conventional and enhanced HCSCs may be effective in reducing the risk of rehospitalization. Further studies are necessary to confirm the medical functions performed by HCSCs.

Coffee consumption and skeletal muscle mass: WASEDA'S Health Study.

Few studies have examined the association between coffee consumption and muscle mass; their results are conflicting. Therefore, we examined the association between coffee consumption and low muscle mass prevalence. We also performed an exploratory investigation of the potential effect modification by demographic, health status-related and physical activity-related covariates. This cross-sectional study included 2085 adults aged 40-87 years. The frequency of coffee consumption was assessed using a self-administered questionnaire. Muscle mass was assessed as appendicular skeletal muscle mass/height2 using a multifrequency bioelectrical impedance analyser. We defined low muscle mass using cut-offs recommended by the Asian Working Group for Sarcopenia. Multivariable-adjusted OR for low muscle mass prevalence were estimated using a logistic regression model. The prevalence of low muscle mass was 5·4 % (n 113). Compared with the lowest coffee consumption group (< 1 cup/week), the multivariable-adjusted OR (95 % CI) of low muscle mass prevalence were 0·62 (0·30, 1·29) for 1-3 cups/week, 0·53 (0·29, 0·96) for 4-6 cups/week or 1 cup/d and 0·28 (0·15, 0·53) for ≥ 2 cups/d (P for trend < 0·001). There were no significant interactions among the various covariates after Bonferroni correction. In conclusion, coffee consumption may be inversely associated with low muscle mass prevalence.

Evaluation of enhanced home care support clinics regarding emergency home visits, hospitalization, and end-of-life care: a retrospective cohort study in a city of Japan.

BACKGROUND: To meet the increasing demand for home healthcare in Japan as the population ages, home care support clinics/hospitals (HCSCs) and enhanced HCSCs were introduced in 2006 and 2012, respectively. This study aimed to evaluate whether enhanced HCSCs fulfilled the expected role in home healthcare. METHODS: We conducted a retrospective cohort study using linked medical and long-term care claims data from a municipality in Japan. Participants were ≥ 65 years of age, had newly started regular home visits between July 2014 and March 2018, and used either conventional or enhanced HCSCs. Patients were followed up for one year after they started regular home visits or until the month following the end of the regular home visits if they ended within one year. The outcome measures were (i) emergency home visits at all hours and on nights and holidays at least once, respectively, (ii) hospitalization at least once, and (iii) end-of-life care, which was evaluated based on the place of death and whether a physician was present at the time of in-home death. Multivariable logistic regression analyses were conducted for the outcomes of emergency home visits and hospitalizations. RESULTS: The analysis included 802 patients, including 405 patients in enhanced HCSCs and 397 patients in conventional HCSCs. Enhanced HCSCs had more emergency home visits at all hours than conventional HCSCs (65.7% vs. 49.1%; adjusted odds ratio 1.70, 95% CI [1.26-2.28]), more emergency home visits on nights and holidays (33.6% vs. 16.7%; 2.20 [1.55-3.13]), and fewer hospitalizations (21.5% vs. 32.2%; 0.55 [0.39-0.76]). During the follow-up period, 229 patients (152 patients in enhanced HCSCs and 77 patients in HCSCs) died. Deaths at home were significantly more common in enhanced HCSCs than in conventional HCSCs (80.9% vs. 64.9%; p < .001), and physician-attended deaths among those who died at home were also significantly more common in enhanced HCSCs (99.2% vs. 78.0%; p < .001). CONCLUSIONS: This study confirms that enhanced HCSCs are more likely to be able to handle emergency home visits and end-of-life care at home, which are important medical functions in home healthcare. Further promotion of enhanced HCSCs would be advantageous.

Association between alcohol dietary pattern and prevalence of dyslipidaemia: WASEDA'S Health Study.

The association between a dietary pattern characterised by high alcohol intake and dyslipidaemia has not been fully investigated. Therefore, the present study aimed to investigate the association between alcohol dietary patterns and the prevalence of dyslipidaemia and its components. This cross-sectional study enrolled 2171 men and women aged ≥40 years who were alumni of a Japanese university. To identify dietary patterns, a principal component analysis was performed based on the energy-adjusted food intake estimated by a brief-type self-administered diet history questionnaire. Three dietary patterns were identified, the second of which was named the alcohol dietary pattern and was characterised by a high intake of alcoholic beverages, liver, chicken and fish. This alcohol dietary pattern was associated with reduced LDL-cholesterol levels. The fully adjusted OR (95 % CI) of high LDL-cholesterol for the lowest through highest quartile of alcohol dietary pattern score were 1·00 (reference), 0·83 (0·64, 1·08), 0·84 (0·64, 1·10) and 0·68 (0·49, 0·94), respectively. Subgroup analysis showed that the alcohol dietary pattern was inversely associated with the prevalence of dyslipidaemia in women, whereas it was positively associated with high TAG levels in men. In conclusion, the alcohol dietary pattern, characterised by a high intake of alcoholic beverages, liver, chicken and fish, was associated with the prevalence of dyslipidaemia and its components. This finding provides useful information for the prevention and treatment of dyslipidaemia by modifying the diet.

Distortion of double-stranded DNA structure by the binding of the restriction DNA glycosylase R.PabI.

R.PabI is a restriction DNA glycosylase that recognizes the sequence 5'-GTAC-3' and hydrolyses the N-glycosidic bond of adenine in the recognition sequence. R.PabI drastically bends and unwinds the recognition sequence of double-stranded DNA (dsDNA) and flips the adenine and guanine bases in the recognition sequence into the catalytic and recognition sites on the protein surface. In this study, we determined the crystal structure of the R.PabI-dsDNA complex in which the dsDNA is drastically bent by the binding of R.PabI but the base pairs are not unwound. This structure is predicted to be important for the indirect readout of the recognition sequence by R.PabI. In the complex structure, wedge loops of the R.PabI dimer are inserted into the minor groove of dsDNA to stabilize the deformed dsDNA structure. A base stacking is distorted between the two wedge-inserted regions. R.PabI is predicted to utilize the distorted base stacking for the detection of the recognition sequence.

The combination of cardiorespiratory fitness and muscular fitness, and prevalence of diabetes mellitus in middle-aged and older men: WASEDA'S Health Study.

BACKGROUND: Although the negative relationship between cardiorespiratory fitness (CRF) or muscular fitness and diabetes mellitus were respectively observed in many previous studies, there is still a lack of studies that include CRF and muscular fitness simultaneously. Therefore, this study aimed to investigate the relationship between the combination of CRF and muscular fitness and diabetes through a cross-sectional study.  METHODS: This study was part of WASEDA'S Health Study, a cohort study launched in 2014. We used a part of the baseline data collected for this study. Maximal exercise test using a cycle ergometer and leg extension power (LEP) test were respectively used to evaluate CRF and muscular fitness. Since LEP is affected by body weight, relative LEP (rLEP) which is LEP per body weight, was used as an index of muscular fitness. 796 men (56.5 ± 10.4 years old) who completed a medical examination and fitness tests, were divided into two groups based on CRF and rLEP, respectively. The prevalence of diabetes was collected based on a self-reported questionnaire or blood test. Odds ratios and 95% confidence intervals (CIs) for the prevalence of diabetes were obtained using logistic regression models while adjusting for age, body mass index, exercise habits, family history of diabetes, smoking habits, and drinking habits. RESULTS: 55 (7%) participants had diabetes. Compared to participants with lower CRF or rLEP, the odds ratio (95% CIs) of diabetes in those with higher CRF or rLEP was 0.46 (0.21-0.98) or 0.34 (0.16-0.74), respectively. Furthermore, using the lower CRF and lower rLEP group as the reference, the odds ratio (95% CIs) for the lower CRF and higher rLEP group was 0.32 (0.12-0.88), and higher CRF and higher rLEP group was 0.21 (0.07-0.63), after adjusting for potential confounding factors. CONCLUSIONS: CRF and rLEP have independent and joint inverse associations with diabetes prevalence. In addition, participants with high CRF and high rLEP had a lower prevalence of diabetes compared to those with only high CRF or only high rLEP.

Contribution of copy number variations to the risk of severe eating disorders.

AIM: Eating disorders (EDs) are complex, multifactorial psychiatric conditions. Previous studies identified pathogenic copy number variations associated with NDDs (NDD-CNVs) in ED patients. However, no statistical evidence for an association between NDD-CNVs and EDs has been demonstrated. Therefore, we examined whether NDD-CNVs confer risk for EDs. METHODS: Using array comparative genomic hybridization (aCGH), we conducted a high-resolution CNV analysis of 71 severe female ED patients and 1045 female controls. According to the American College of Medical Genetics guidelines, we identified NDD-CNVs or pathogenic/likely pathogenic CNVs in NDD-linked loci. Gene set analysis was performed to examine the involvement of synaptic dysfunction in EDs. Clinical data were retrospectively examined for ED patients with NDD-CNVs. RESULTS: Of the samples analyzed with aCGH, 70 severe ED patients (98.6%) and 1036 controls (99.1%) passed our quality control filtering. We obtained 189 and 2539 rare CNVs from patients and controls, respectively. NDD-CNVs were identified in 10.0% (7/70) of patients and 2.3% (24/1036) of controls. Statistical analysis revealed a significant association between NDD-CNVs and EDs (odds ratio = 4.69, P = 0.0023). NDD-CNVs in ED patients included 45,X and deletions at KATNAL2, DIP2A, PTPRT, RBFOX1, CNTN4, MACROD2, and FAM92B. Four of these genes were related to synaptic function. In gene set analysis, we observed a nominally significant enrichment of rare exonic CNVs in synaptic signaling in ED patients (odds ratio = 2.55, P = 0.0254). CONCLUSION: Our study provides the first preliminary evidence that NDD-CNVs may confer risk for severe EDs. The pathophysiology may involve synaptic dysfunction.

[Validation of using disqualification from long-term care insurance registry as a proxy of death].

Objectives　The national database for long-term care insurance (LTCI) of Japan (Kaigo DB) enables researchers to access comprehensive data from its LTCI registry, eligibility assessment records, claims for service usage, and information about service providers. However, studies regarding the death or mortality of beneficiaries cannot be conducted because Kaigo DB does not contain death records, and researchers are not allowed to link Kaigo DB to other databases, such as national death records. Therefore, we aimed to assess the validity of using an insurer's disqualification from an LTCI beneficiary as a proxy of death.Methods　We used 510,751,798 monthly beneficiary records between April 2007 and March 2017 from the LTCI registry, while excluding data for ineligible persons for LTCI benefit or those younger than 65 years. We identified insurer cases disqualified from LTCI beneficiaries and linked them to national death records using deterministic linkage methods by dates of birth and death, sex, and residence. We considered the cases as positive if they were disqualified and their record was linked to a death. We used sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) as validity indices.Results　We identified 5,986,991 (1.17%) disqualified and 5,295,961 death cases. Sensitivity, specificity, PPV, and NPV of disqualification for death were 100%, 99.86%, 88.46%, and 100%, respectively. After stratification, PPV of disqualification was between 85% and 88% before 2012, 91% after 2012, 91.9% in men, and 85.9% in women. PPV increased with age (65-69 years: 80.6%, 70-74 years: 86.7%, 75-79 years: 86.4%, 80-84 years: 86.7%, 85-89 years: 88.0%, 90-94 years: 90.6%, and 95+ years: 93.4%) and level of care needed (support level: 72.2%, care level (CL) 1: 79.7%, CL2: 85.9%, CL3: 89.3%, CL4: 92.3%, and CL5: 94.0%).Conclusions　Disqualification from the LTCI registry is an inappropriate measure to estimate mortality accurately because it has a 10% false-positive rate. However, it appears sufficiently valid to use disqualification as a proxy outcome of death, although the main effect or confounding of a possible predictor of death could be slightly underestimated.

Prevention services via public long-term care insurance can be effective among a specific group of older adults in Japan.

BACKGROUND: To evaluate the effects of prevention services provided by long-term care insurance (LTCI) for older adults who require support from LTCI in Kashiwa City, Japan. METHODS: We conducted an analysis using the following population-based longitudinal data in Kashiwa City between April 2012 and March 2015: Data of National Health Insurance and LTCI claims, the survey for certification of LTCI, the register, and premium tier classification. All data was linked using the pre-assigned anonymous identifying numbers. We analyzed the Cox regression model using the time for the deteriorations of levels of certified care need in LTCI as an outcome and the use of preventive care services as the primary exposure among participants aged 75 years or older, who had either support levels 1 or 2 at the beginning of this analysis. The study was further stratified by both age and initial support level. RESULTS: The final analysis included 1289 participants. The primary result showed, among all participants, that preventive service was not effective (hazard ratio 0.96, 95% confidence interval 0.78-1.19). In our sub-analysis, the preventive service was effective in avoiding deteriorations only among those aged 85 and older with support level 1 (HR 0.65, 95% CI 0.43-0.97) out of four groups. CONCLUSIONS: The preventive services of LTCI in Kashiwa City showed a significant effect on the deterioration among subjects aged 85 or older, whose disability level were low (support level 1). Our results suggest that the prevention services provided by LTCI may not be effective for all older individuals; to provide these services efficiently, local governments, as insurers of LTCI, will need to identify the specified groups that may benefit from the preventive services. Additionally, it is necessary to re-examine what preventive interventions may be effective, or redesign the health system if necessary, for those who were not affected by the intervention.

Autologous Induced Stem-Cell-Derived Retinal Cells for Macular Degeneration.

We assessed the feasibility of transplanting a sheet of retinal pigment epithelial (RPE) cells differentiated from induced pluripotent stem cells (iPSCs) in a patient with neovascular age-related macular degeneration. The iPSCs were generated from skin fibroblasts obtained from two patients with advanced neovascular age-related macular degeneration and were differentiated into RPE cells. The RPE cells and the iPSCs from which they were derived were subject to extensive testing. A surgery that included the removal of the neovascular membrane and transplantation of the autologous iPSC-derived RPE cell sheet under the retina was performed in one of the patients. At 1 year after surgery, the transplanted sheet remained intact, best corrected visual acuity had not improved or worsened, and cystoid macular edema was present. (Funded by Highway Program for Realization of Regenerative Medicine and others; University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number, UMIN000011929 .).

Low serum albumin, aspartate aminotransferase, and body mass are risk factors for frailty in elderly people with diabetes-a cross-sectional study.

BACKGROUND: Frailty is broadly characterized by vulnerability and decline in physical, mental and social activities and is more common in elderly patients with type 2 diabetes mellitus (T2DM). Frailty is closely associated with nutrition, muscle strength, inflammation, and hormones etc. In hormones, dehydroepiandrosterone sulfate (DHEA-S) and cortisol are suggested to be such candidates affecting frailty. Little investigation has been performed using a wider range of measures of frailty to clarify risk factors for frailty including the above two hormones. METHODS: We performed a cross-sectional study to investigate the risk factors for frailty in elderly T2DM patients (n = 148; ≥65 years), using a broad assessment, the clinical frailty scale. We compared parameters between the non-frail and frail groups using the unpaired t and Mann-Whitney U tests. The Jonckheere-Therpstra test was used to identify relationships with the severity of frailty, and risk factors were identified using binary regression analysis. RESULTS: Simple regression analysis identified a number of significant risk factors for frailty, including DHEAS < 70 µg/dL and cortisol/DHEA-S ratio ≥ 0.2. Multiple regression analysis showed that low albumin (< 4.0 g/dl) (odds ratio [OR] = 5.79, p < 0.001), low aspartate aminotransferase (AST) activity (< 25 IU/L) (OR = 4.34, p = 0.009), and low body mass (BM) (< 53 kg) (OR = 3.85, p = 0.012) were independent risk factors for frailty. A significant decrease in DHEA-S and a significant increase in the cortisol/DHEA-S ratio occurred alongside increases in the severity of frailty. DHEA-S concentration positively correlated with both serum albumin and BM. CONCLUSIONS: Hypoalbuminemia, low AST, and low BM are independent risk factors for frailty in elderly T2DM patients, strongly implying relative malnutrition in these frail patients. DHEA-S may be important for the maintenance of liver function and BM. A decrease in DHEA-S and an increase in the cortisol/DHEAS ratio may be involved in the mechanism of the effect of malnutrition in elderly T2DM patients.

Crystal structure of the novel lesion-specific endonuclease PfuEndoQ from Pyrococcus furiosus.

Because base deaminations, which are promoted by high temperature, ionizing radiation, aerobic respiration and nitrosative stress, produce mutations during replication, deaminated bases must be repaired quickly to maintain genome integrity. Recently, we identified a novel lesion-specific endonuclease, PfuEndoQ, from Pyrococcus furiosus, and PfuEndoQ may be involved in the DNA repair pathway in Thermococcales of Archaea. PfuEndoQ recognizes a deaminated base and cleaves the phosphodiester bond 5' of the lesion site. To elucidate the structural basis of the substrate recognition and DNA cleavage mechanisms of PfuEndoQ, we determined the structure of PfuEndoQ using X-ray crystallography. The PfuEndoQ structure and the accompanying biochemical data suggest that PfuEndoQ recognizes a deaminated base using a highly conserved pocket adjacent to a Zn2+-binding site and hydrolyses a phosphodiester bond using two Zn2+ ions. The PfuEndoQ-DNA complex is stabilized by a Zn-binding domain and a C-terminal helical domain, and the complex may recruit downstream proteins in the DNA repair pathway.

Structural basis for receptor-regulated SMAD recognition by MAN1.

Receptor-regulated SMAD (R-SMAD: SMAD1, SMAD2, SMAD3, SMAD5 and SMAD8) proteins are key transcription factors of the transforming growth factor-ß (TGF-ß) superfamily of cytokines. MAN1, an integral protein of the inner nuclear membrane, is a SMAD cofactor that terminates TGF-ß superfamily signals. Heterozygous loss-of-function mutations in MAN1 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis. MAN1 interacts with MAD homology 2 (MH2) domains of R-SMAD proteins using its C-terminal U2AF homology motif (UHM) domain and UHM ligand motif (ULM) and facilitates R-SMAD dephosphorylation. Here, we report the structural basis for R-SMAD recognition by MAN1. The SMAD2-MAN1 and SMAD1-MAN1 complex structures show that an intramolecular UHM-ULM interaction of MAN1 forms a hydrophobic surface that interacts with a hydrophobic surface among the H2 helix, the strands ß8 and ß9, and the L3 loop of the MH2 domains of R-SMAD proteins. The complex structures also show the mechanism by which SMAD cofactors distinguish R-SMAD proteins that possess a highly conserved molecular surface.

Health Promotion Awareness in Barbershops and Salons: An International Cross-Sectional Survey in Japan and Thailand.

Aging societies are a worldwide concern, as people are living longer than ever before. The success of the "barbershop project" in improving community health in the USA suggests that the aging issue can be tackled using this method even in Asia. Nevertheless, the health promotion awareness of barbers/stylists has barely been reported in Asia. This study aimed to identify the health promotion awareness of barbers and stylists in Japan and Thailand. An international cross-sectional survey was conducted between March and December 2017. Questionnaire contents included the "current status of existing health-promotion-related services," "awareness of contribution to maintaining people's health," and "awareness of collaboration with health care professionals." Participants were 99 Japanese and 101 Thai shop owners. In Japan, more health-promotion-related services were already provided through shops, and health care awareness was higher than in Thailand. In both countries, some shops were willing to collaborate with health care professionals. In Japan, "barbers/stylists have consultation opportunities with health care professionals," "health-related leaflets are provided," "development of therapy/care," and "barbershops/salons become a bridge between communities and hospitals" were mentioned as ideas for collaboration. In conclusion, barbers/stylists are highly interested in health due to the direct connection between beauty and health. Collaboration between barbershops/salons and health care professionals is possible, especially in Japan due to its super-aging society. Further development of the barbershop/salon project is needed.

Increased community-acquired upper urinary tract infections caused by extended-spectrum beta-lactamase-producing Escherichia coli in children and the efficacy of flomoxef and cefmetazole.

BACKGROUND: Urinary tract infections caused by extended-spectrum beta-lactamase-producing bacteria are increasing worldwide. At our hospital, the number of pediatric patients hospitalized because of an upper urinary tract infection has dramatically increased since 2016. In total, 60.5% of urinary tract infections are caused by extended-spectrum beta-lactamase-producing Escherichia coli. Such a high prevalence of extended-spectrum beta-lactamase-producing E. coli has not been detected previously in Japan. Therefore, we evaluated the clinical and bacteriologic characteristics and efficacy of antibiotics against upper urinary tract infections caused by E. coli in children. METHODS: This retrospective study surveyed 152 patients who were hospitalized in the pediatric department of Shimane Prefectural Central Hospital because of upper urinary tract infections caused by E. coli. Medical records were reviewed to examine patient characteristics. O antigens, antibiotic susceptibility, gene typing, and pulse-field gel electrophoresis were studied at the Shimane Prefectural Institute of Public Health and Environmental Science. RESULTS: Urine sample analyses showed extended-spectrum beta-lactamase types such as CTX-M-9 and plural virulence genes. We changed the primary antibiotic treatment to flomoxef or cefmetazole to treat upper urinary tract infections caused by Gram-negative bacilli. After changing treatment, the time to fever alleviation was significantly shortened. CONCLUSION: Extended-spectrum beta-lactamase-producing E. coli should be suspected in community-acquired upper urinary tract infections. Therefore, when treating patients, it is necessary to focus on antibiotic susceptibility and the prevalence of extended-spectrum beta-lactamase-producing bacteria found in each area. Flomoxef and cefmetazole are useful primary treatments for upper urinary tract infections caused by extended-spectrum beta-lactamase-producing E. coli.

Effect of Vitamin D Supplementation on Body Composition and Physical Fitness in Healthy Adults: A Double-Blind, Randomized Controlled Trial.

INTRODUCTION: This study aimed to clarify whether 1 year of vitamin D3 supplementation has a direct effect on body composition and physical fitness in healthy adults. METHODS: Ninety-five participants randomly received either 420 IU vitamin D3 per day (n = 48) or placebo (n = 47) in a double-blind manner for 1 year. Lean body mass and percentage body fat were determined. Physical fitness including hand grip strength, leg extension power and cardiorespiratory fitness (CRF) were assessed. Serum 25-hydroxyvitamin D (25[OH]D) and 1,25-dihydroxyvitamin D (1,25[OH]2D) concentrations were assessed using ELISA kits. RESULTS: Serum 25(OH)D and (1,25[OH]2D) concentrations significantly increased by approximately 11.2 ± 9.2 ng/mL (pinteraction <0.001)and 7.0 ± 7.8 pg/mL (pinteraction <0.001) after 1 year of vitamin D3 supplementation respectively. Lean body mass significantly increased from 43.8 ± 9.6 to 44.3 ± 9.8 kg in vitamin D group, while no change was observed in placebo group (from 42.6 ± 8.9 to 42.4± 8.9 kg) after 1 year intervention. Furthermore, no treatment effects on other indicators of body composition and physical fitness were observed. CONCLUSIONS: One year of vitamin D supplementation effectively improves lean body mass, but not muscle strength and CRF in healthy adults.