The structure of the rat vitamin B12 transporter TC and its complex with glutathionylcobalamin.

Vitamin B12 (cobalamin or Cbl) functions as a cofactor in two important enzymatic processes in human cells, and life is not sustainable without it. B12 is obtained from food and travels from the stomach, through the intestine, and into the bloodstream by three B12-transporting proteins: salivary haptocorrin (HC), gastric intrinsic factor, and transcobalamin (TC), which all bind B12 with high affinity and require proteolytic degradation to liberate Cbl. After intracellular delivery of dietary B12, Cbl in the aquo/hydroxocobalamin form can coordinate various nucleophiles, for example, GSH, giving rise to glutathionylcobalamin (GSCbl), a naturally occurring form of vitamin B12. Currently, there is no data showing whether GSCbl is recognized and transported in the human body. Our crystallographic data shows for the first time the complex between a vitamin B12 transporter and GSCbl, which compared to aquo/hydroxocobalamin, binds TC equally well. Furthermore, sequence analysis and structural comparisons show that TC recognizes and transports GSCbl and that the residues involved are conserved among TCs from different organisms. Interestingly, haptocorrin and intrinsic factor are not structurally tailored to bind GSCbl. This study provides new insights into the interactions between TC and Cbl.

Effectiveness of e-learning material on essential components of evidence-based medicine among laypersons: a randomized controlled trial.

Evidence-based medicine (EBM) is helpful for laypersons' decision-making. This study aimed to evaluate the effectiveness of e-learning materials on the essential components of EBM for laypersons. We conducted a web-based, open-label, randomized controlled trial with laypersons in Japan aged ≥20 years who used the internet. Participants were randomly assigned to the intervention group with the e-learning material and the control group with only the 'Introduction' section of the same material. The primary and secondary outcomes were the self-created acquirement test scores (responding correctly with confidence) immediately after using the material and after 4 weeks. A multiple linear regression analysis was conducted. Of the 122 participants, 62 were randomly assigned to the intervention group and 59 to the control group; finally, 59 and 58, respectively, were included in the full analysis set. The mean (standard deviation) of the acquirement test score immediately after learning was 14.11 and (3.11) and 11.07 (3.88) in the intervention and control groups, respectively, indicating statistical significance (multivariable P < 0.001). The secondary long-term outcome was also statistically significant. The results showed that the e-learning material was effective for laypersons in acquiring the essential components of EBM. The material may increase laypersons' confidence in appraising health information, which can be used in decision-making.

Does endoscopic sphincterotomy contribute to the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis after endoscopic biliary stenting for malignant biliary obstruction? A multicenter prospective cohort study.

BACKGROUND: There is no consensus on the necessity of endoscopic sphincterotomy (ES) to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) after endoscopic stenting in patients with malignant biliary obstruction. We investigated the incidence of PEP after endoscopic biliary stenting for malignant biliary obstruction with or without ES in a multicenter prospective cohort study. METHODS: We enrolled 807 patients who underwent endoscopic biliary stenting for malignant biliary obstruction with a native papilla at 36 hospitals between April 2017 and March 2018. The incidence of PEP in patients with or without ES was compared for subgroups based on stent type, placement method, and patient background. Univariate and multivariate analysis was performed to investigate the incidence of PEP in all stenting patients. RESULTS: Plastic and metal stents (MS) were inserted in 598 and 209 patients, respectively. The incidence of PEP in patients with or without ES was 7.9% and 7.4%, respectively among all stenting patients. The incidences of PEP with or without ES in plastic stent insertion patients, patients with MS insertion, stent insertions across the papilla, stent insertions across the papilla in patients without main pancreatic duct obstruction, and fully covered MS insertions across the papilla were compared. There was no overall significant difference in the incidence of PEP between those with or without ES. Multivariate logistic regression analysis for the incidence of PEP in all stenting patients revealed obstruction of the main pancreatic duct at the pancreatic head and epinephrine spraying on the papilla were significant factors; there was no significant difference in the incidence of PEP between patients with or without ES. CONCLUSION: Endoscopic sphincterotomy may not contribute to the prevention of PEP after endoscopic biliary stenting for malignant biliary obstruction, even in cases of insertion with a fully covered MS across the papilla.

The development of a prediction model for arrest of labour to be used at regular check-ups, during 36 or 37 gestational weeks, for primiparas: a retrospective cohort study.

PURPOSE: An emergency caesarean section (CS) has more complications than a planned CS. The arrest of labour is a major indication for an emergency CS. This study aimed to develop a prediction model for the arrest of labour to be used in regular check-ups at 36 or 37 gestational weeks for primiparas. METHODS: This was a retrospective cohort study conducted at a single institution in Japan using data from January 2007 to December 2013. Primiparas attending regular check-ups during 36 or 37 gestational weeks, with live single foetuses in a cephalic presentation were included. The outcome was the incidence of labour arrest. Candidate predictors included 25 maternal and foetal findings. We developed a prediction model using logistic regression analysis with stepwise selection. A score was assigned to each predictor of the final model based on their respective ß coefficients. RESULTS: A total of 739 women were included in the analysis. Arrest of labour was diagnosed in 47 women (6.4%), and all of them delivered by emergency CS. The predictors in the final model were a Bishop score ≤ 1, maternal height ≤ 154 cm, foetal biparietal diameter ≥ 91 mm, pre-pregnancy weight ≥ 54 kg, maternal haemoglobin concentration ≥ 11.0 g/dl, and amniotic fluid index ≥ 13. The area under the receiver operating characteristic curve was 0.783. CONCLUSION: We have developed the first model to predict arrested labour before its onset. Although this model requires validation using external samples, it will help clinicians and pregnant women to control gestational conditions and make decisions regarding planned CS.

Effects of oral health-related quality of life on total mortality: a prospective cohort study.

BACKGROUND: The effects of oral health on mortality have been reported; however, the association between mortality and Oral Health-Related Quality of Life (OHQOL) is unknown. We investigated the effect of OHQOL on total mortality in a cohort consisting of dentists. METHODS: In this cohort study, we analyzed data from the Longitudinal Evaluation of Multi-phasic, Odonatological and Nutritional Associations in Dentists study. We conducted a baseline survey of general and oral health factors. We called for 31,178 participants and collected responses from 10,256 participants. We followed up with 10,114 participants (mean age ± standard deviation, 52.4 ± 12.1 years; females, 8.9%) for 7.7 years, until March 2014, to determine the average total mortality. OHQOL was assessed using the General Oral Health Assessment Index (GOHAI). The total score was divided into quartiles (Q1 ≤ 51.6, Q2 = 51.7-56.7, Q3 = 56.8-59.9, and Q4 = 60.0), with higher GOHAI scores indicating better OHQOL (score range, 12-60). The association between OHQOL and total mortality was analyzed using the Cox proportional hazards model. RESULTS: We documented 460 deaths. Males with low GOHAI scores possessed a remarkably high risk of total mortality. The multivariate adjusted-hazard ratios (aHRs), were 1.93 (95% confidence interval [CI], 1.07 - 3.48) for Q1, 1.69 (95% CI, 0.90 - 3.17) for Q2, and 0.65 (95% CI, 0.29 - 1.46) for Q3, relative to Q4 (trend p = 0.001). The aHRs in the multivariate model with all background variables were 1.69 (95% CI, 1.15-2.46) for Q1, 1.53 (95% CI, 1.04-2.27) for Q2, and 1.09 (95% CI, 0.71-1.70) for Q3, relative to Q4 (trend p = 0.001). In females, there was no significant association between the quartiles, in both the multivariate-adjusted model (trend p = 0.52) and multivariate-adjusted model with all background variables (trend p = 0.79). CONCLUSIONS: A lower OHQOL indicated an increased risk of total mortality in dentists. OHQOL may be used as an indicator for selecting treatment plans and personalized care interventions, thus contributing to increased healthy life expectancy. TRIAL REGISTRATION: Aichi Cancer Center, Nagoya University Graduate School of Medicine, and Hiroshima University (Approval numbers: 33, 632-3, 8-21, and E2019-1603).

Temporal change in the association between life satisfaction and functional decline with gender differences: an age-specific prospective cohort study.

BACKGROUND: Although life satisfaction (LS) has been shown to predict mortality, research studying the relationship between LS and functional decline is scarce. This study examined the association between LS and functional decline across four time points in young-old Japanese adults. METHODS: We analysed 1,899 community-dwelling 65-year-olds in this age-specific cohort study conducted between 2000 and 2005. The Life Satisfaction Index K was used to evaluate LS and was classified into quartiles. Functional decline was determined using the Japanese Long-Term Care Insurance (LTCI) system: 1) mild disability; 2) severe disability; 3) all-cause mortality; 4) mild or severe disability; 5) severe disability or death; 6) mild or severe disability, or death. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) were calculated using the Cox proportional hazard model. The analyses were conducted in the 8th, 10th, 12th, and 14th years to assess the effect of LS on functional decline across time points. RESULTS: The impact of LS gradually weakened over time. In the 8th year (aged 72-73), a higher LS was associated with a lower risk of mild or severe disability among the women participants (adjusted HR [95% CI] = 0.30 [0.11-0.81]). However, the effect disappeared gradually (adjusted HR [95% CI] = 0.55 [0.27-1.14]) in the 10th year (aged 74-75), 0.72 (0.41-1.26) in the 12th year (aged 76-77), and 0.68 (0.41-1.14) in the 14th year (aged 78-79). This trend continued in severe disability or death (adjusted HR [95% CI] = 0.24 [0.06-0.70], 0.31 [0.11-0.76], 0.57 [0.28-1.14], and 0.60 [0.32-1.12]) and mild or severe disability, or death (adjusted HR [95% CI] = 0.30 [0.14-0.68], 0.46 [0.24-0.87], 0.67 [0.41-1.10], and 0.65 [0.42-1.02]) in the 8th, 10th, 12th, and 14th years, respectively. No statistically significant association was found among men at any time points or in any classification of outcomes. CONCLUSIONS: Higher LS scores in 65-year-old women were associated with a lower risk for functional decline in any combination of mild disability, severe disability, or death. Additionally, the effect of LS was observed to weaken over time. TRIAL REGISTRATION: This is not an intervention survey and does not require registration.

Guidelines for de novo phasing using multiple small-wedge data collection. Corrigendum.

A figure in the article by Baba et al. [(2021), J. Synchrotron Rad. 28, 1284-1295] is corrected.

Laypersons' Psychological Barriers Against Rescue Actions in Emergency Situations　- A Questionnaire Survey.

BACKGROUND: Although bystanders' performance is important to improve outcomes of patients after cardiac arrests, few studies have investigated the barriers of bystanders, including those who could not perform cardiopulmonary resuscitation or any other rescue actions in emergency situations. This study aimed to assess the relationship between the psychological barriers of laypersons who encountered emergency situations and their rescue actions.Methods and Results:A questionnaire survey was conducted and this included laypersons who had encountered emergency situations during the last 5 years. Six questions were about the psychological barriers and 8 questions were about the laypersons' rescue actions. The primary outcome was any rescue actions performed by laypersons in an actual emergency situation. Overall, 7,827 (92.8%) of 8,430 laypersons responded; of them, 1,361 (16.1%) had encountered emergency situations during the last 5 years, and 1,220 (14.5%) were eligible for inclusion in the analyses. Of the 6 psychological barriers, "fear of approaching a collapsed person" (adjusted odds ratio [AOR] 0.50; 95% confidence interval [95% CI] 0.32-0.79) and "difficulties in judging whether to perform any rescue action" (AOR 0.63; 95% CI 0.40-0.99) were significantly associated with performing any rescue actions. CONCLUSIONS: The fear of approaching a collapsed person and difficulties in judging whether to take any actions were identified as the psychological barriers in performing any rescue actions by laypersons who encountered emergency situations.

Changes in behavioral activities and transition of depressive symptoms among younger-old community-dwelling adults during 6 years: An age-specific prospective cohort study.

OBJECTIVE: Regular engagement in behavioral activities plays a crucial role against depressive symptoms in older adults. This study aims to explore the relationship between behavioral activities and the temporal evolution of depressive symptoms. METHODS: We included community-dwelling Japanese adults aged 64 or 65 years with and without depressive symptoms enrolled in the New Integrated Suburban Seniority Investigation (NISSIN) project. Depressive symptoms at baseline and follow-up were assessed using the 15-item Geriatric Depression Scale. Behavioral activities were measured by self-reported questions. Risk ratios and 95% confidence intervals were calculated using modified Poisson regression, adjusting for relevant sociodemographic variables and health-related confounders. RESULTS: During the 6 year follow-up period, 139 (10.1%) without depressive symptoms at baseline developed such symptoms over time, while 174 (51.6%) with depressive symptoms improved to the point of these symptoms being absent. The participants without depressive symptoms at baseline and those who engaged in social activity or daily walking at a continued regular frequency (CRF) or an increased frequency (IF) and exercise habits at CRF were the least likely to have depressive symptoms onset at follow-up. There was no significant difference between the changes in behavioral activities and the improvement of depressive symptoms after controlling for confounders. Participants engaging in a greater variety of behavioral activities at CRF were less likely to experience a new onset of depressive symptoms. CONCLUSIONS: Consistent and regular participation in one or more behavioral activities was significantly associated with the onset of depressive symptoms in Japanese community-dwelling older adults.

Accidental epidural catheter removal rates and strength required for disconnection: a retrospective cohort and laboratory study.

BACKGROUND: Epidural catheters are associated with certain risks such as accidental epidural catheter removal, including dislodgement and disconnection. Globally, neuraxial connector designs were revised in 2016 to provide new standardization aimed at decreasing the frequency of misconnections during the administration of medications. However, no studies have investigated accidental epidural catheter removal after the revised standardization. This study aimed to examine differences in dislodgement and disconnection rates associated with different catheter connector types, and to investigate the linear tensile strength required to induce disconnection. METHODS: This retrospective cohort study included adult patients who underwent elective surgery and received patient-controlled epidural analgesia. Patients were divided into groups according to the type of catheter connection used: old standard, new standard, and new standard with taping groups. Furthermore, we prepared 60 sets of epidural catheters and connectors comprising 20 sets for each of the old, new, and taping groups, and used a digital tension meter to measure the maximum tensile strength required to induce disconnection. RESULTS: This clinical study involved 360, 182, and 378 patients in the old, new, and taping groups, respectively. Dislodgement rates did not differ statistically among the three groups, while there was a significant difference in disconnection rates. Propensity score matching analysis for disconnection rates showed no difference between the old and new groups (2.8% vs. 4.5%, p = 0.574), while the new group had higher rates than the taping group (6.5% vs. 0%, p = 0.002). This laboratory study identified that a tensile strength of 12.41 N, 12.06 N, and 19.65 N was required for disconnection in the old, new, and taping groups, respectively, and revealed no significant difference between the new and old groups (p = 0.823), but indicated a significant difference between the new and taping groups (p < 0.001). CONCLUSIONS: This clinical study suggested that dislodgement rates did not change among the three groups. Both clinical and laboratory studies revealed that disconnection rates did not change between the old and new connectors. Moreover, as a strategy to prevent accidents, taping the connecting points of the catheter connectors led to an increase in the tensile strength required for disconnection.

Multicenter prospective cohort study of adverse events associated with biliary endoscopic retrograde cholangiopancreatography: Incidence of adverse events and preventive measures for post-endoscopic retrograde cholangiopancreatography pancreatitis.

OBJECTIVES: The reported incidence of adverse events (AEs) in endoscopic retrograde cholangiopancreatography (ERCP) varies between 2.5% and 14%. The aim of this study was to evaluate the incidence and severity of AEs in biliary ERCP and to specify the risk factors and preventive measures for post-ERCP pancreatitis (PEP). METHODS: Patients with biliary disease with intact papilla were prospectively enrolled at 36 hospitals between April 2017 and March 2018. The primary outcomes were the incidence and severity of AEs. RESULTS: A total of 16,032 ERCP procedures were performed at the 36 hospitals during the study period and 3739 patients were enrolled. The overall incidence of AEs was 10.1% and ERCP-related mortality was 0.08%. PEP developed in 258 cases (6.9%), bleeding in 33 (0.9%), instrumental AEs in 17 (0.5%), infections in 37 (1.0%), cardiovascular AEs in eight (0.2%), pulmonary AEs in eight (0.2%), drug reaction AE in one (0.03%), pain in 15 (0.4%), and other AEs in 15 (0.4%). Multivariable analysis showed significant risk factors for PEP were: female of younger age, pancreatic guidewire-assisted biliary cannulation, temporary guidewire insertion into the pancreatic duct, total procedure time >60 min, and post-ERCP administration of non-steroidal anti-inflammatory drugs. Effective preventive measures were prophylactic pancreatic stenting (PPS) and epinephrine spraying onto the papilla. CONCLUSIONS: In patients with intact papilla who underwent biliary ERCP, the incidence of AEs was 10.1% and the mortality was 0.08%. PPS and epinephrine spraying may prevent PEP. REGISTRATION: This study was registered in the University Hospital Medical Information Network (UMIN000024820).

Optimized Simulation of Upper Body Timing on the Production of Bat-Head Speed in Baseball Batting.

The objectives of this study were to (1) investigate the effect of the timing of the upper body joint motions in baseball batting on the bat-head speed and (2) develop and evaluate a simulation model inputting the individual hand forces on the bat. Twenty-three male collegiate baseball players performed tee batting set at waist height. A 10-segment angle-driven simulation model consisting of a bat and upper body was driven using the coordinate data of the standard motion. Performance optimization was conducted by changing the timing of the joint angle time histories of the upper body to increase the maximum bat-head speed. The optimization simultaneously estimated the individual hand forces by polynomial approximation dependent on the total bat forces to assess joint torques of the upper body. The bat-head speed increased to 39.2 m/s from 35.6 m/s, and the optimized timings were characterized by the earlier timing of the barrel-side elbow supination, wrist radial flexion, torso right lateral flexion, and the later timing of the barrel-side shoulder abduction. It is concluded that the skillful coordination of the individual joint movements for the upper body can produce a higher bat-head speed through effective sequencing of proximal to distal movements.

Oncogenic mutations Q61L and Q61H confer active form-like structural features to the inactive state (state 1) conformation of H-Ras protein.

GTP-bound forms of Ras proteins (Ras•GTP) assume two interconverting conformations, "inactive" state 1 and "active" state 2. Our previous study on the crystal structure of the state 1 conformation of H-Ras in complex with guanosine 5'-(ß, γ-imido)triphosphate (GppNHp) indicated that state 1 is stabilized by intramolecular hydrogen-bonding interactions formed by Gln61. Since Ras are constitutively activated by substitution mutations of Gln61, here we determine crystal structures of the state 1 conformation of H-Ras•GppNHp carrying representative mutations Q61L and Q61H to observe the effect of the mutations. The results show that these mutations alter the mode of hydrogen-bonding interactions of the residue 61 with Switch II residues and induce conformational destabilization of the neighboring regions. In particular, Q61L mutation results in acquirement of state 2-like structural features. Moreover, the mutations are likely to impair an intramolecular structural communication between Switch I and Switch II. Molecular dynamics simulations starting from these structures support the above observations. These findings may give a new insight into the molecular mechanism underlying the aberrant activation of the Gln61 mutants.

Guidelines for de novo phasing using multiple small-wedge data collection.

Intense micro-focus X-ray beamlines available at synchrotron facilities have achieved high-quality data collection even from the microcrystals of membrane proteins. The automatic data collection system developed at SPring-8, named ZOO, has contributed to many structure determinations of membrane proteins using small-wedge synchrotron crystallography (SWSX) datasets. The `small-wedge' (5-20°) datasets are collected from multiple crystals and then merged to obtain the final structure factors. To our knowledge, no systematic investigation on the dose dependence of data accuracy has so far been reported for SWSX, which is between `serial crystallography' and `rotation crystallography'. Thus, herein, we investigated the optimal dose conditions for experimental phasing with SWSX. Phase determination using anomalous scattering signals was found to be more difficult at higher doses. Furthermore, merging more homogeneous datasets grouped by hierarchical clustering with controlled doses mildly reduced the negative factors in data collection, such as `lack of signal' and `radiation damage'. In turn, as more datasets were merged, more probable phases could be obtained across a wider range of doses. Therefore, our findings show that it is essential to choose a lower dose than 10 MGy for de novo structure determination by SWSX. In particular, data collection using a dose of 5 MGy proved to be optimal in balancing the amount of signal available while reducing the amount of damage as much as possible.

Prediction of 11-year incidence of psychophysically dependent status or death among community-dwelling younger elderlies: from an age-specified community-based cohort study (the NISSIN project).

BACKGROUND: Predicting adverse health events and implementing preventative measures are a necessary challenge. It is important for healthcare planners and policymakers to allocate the limited resource to high-risk persons. Prediction is also important for older individuals, their family members, and clinicians to prepare mentally and financially. The aim of this study is to develop a prediction model for within 11-year dependent status requiring long-term nursing care or death in older adults for each sex. METHODS: We carried out age-specified cohort study of community dwellers in Nisshin City, Japan. The older adults aged 64 years who underwent medical check-up between 1996 and 2000 were included in the study. The primary outcome was the incidence of the psychophysically dependent status or death or by the end of the year of age 75 years. Univariable logistic regression analyses were performed to assess the associations between candidate predictors and the outcome. Using the variables with p-values less than 0.1, multivariable logistic regression analyses were then performed with backward stepwise elimination to determine the final predictors for the model. RESULTS: Of the 1525 female participants at baseline, 105 had an incidence of the study outcome. The final prediction model consisted of 15 variables, and the c-statistics for predicting the outcome was 0.763 (95% confidence interval [CI] 0.714-0.813). Of the 1548 male participants at baseline, 211 had incidence of the study outcome. The final prediction model consisted of 16 variables, and the c-statistics for predicting the outcome was 0.735 (95% CI 0.699-0.771). CONCLUSIONS: We developed a prediction model for older adults to forecast 11-year incidence of dependent status requiring nursing care or death in each sex. The predictability was fair, but we could not evaluate the external validity of this model. It could be of some help for healthcare planners, policy makers, clinicians, older individuals, and their family members to weigh the priority of support.

Characteristics and Outcomes of Out-of-Hospital Cardiac Arrest in Educational Institutions in Japan　- All-Japan Utstein Registry.

BACKGROUND: Although schools are key places that conduct cardiopulmonary resuscitation (CPR) and public-access defibrillation (PAD) programs, out-of-hospital cardiac arrest (OHCA) in educational institutions is poorly understood. This study describes the characteristics and outcomes of such OHCAs.Methods and Results:Data for OHCAs of any cause occurring in educational institutions between 2013 and 2015 were extracted from the All-Japan Utstein Registry. Patient characteristics and outcomes were documented. Subjects were divided into 6 age groups (0-1, 2-5, 6-11, 12-14, 15-17, and ≥18 years). Among the 783 eligible OHCA patients, most received bystander CPR regardless of age, ranging from 73.9% in those aged ≥18 years to 90.0% in those aged 2-5 years. However, the proportion receiving PAD differed by age group, ranging from 2.9% in those aged 0-1 years to 66.7% in those aged 12-14 years. The proportion of patients with 1-month survival with favorable neurological outcome differed significantly by age group, being extremely low among patients aged 0-1 years (zero for OHCA of cardiac origin), but high among patients aged 6-11, 12-14, and 15-17 years (69.2%, 77.5%, and 70.0%, respectively) for OHCA of cardiac origin. CONCLUSIONS: The outcomes of OHCA occurring in educational institutions, where PAD is available, differed significantly by age.

The association between depressive symptoms and self-rated health among university students: a cross-sectional study in France and Japan.

BACKGROUND: Depressive disorders in University students have risen dramatically in the past few decades to the extent that students' mental health has become a current global public health priority. Obtaining information from University students about their mental health is challenging because of potential embarrassment of disclosing one's concerns and fear of stigmatization. Self-rated health might be a good solution to evaluate mental health state by a simple and neutral indicator. The aim of the study is to investigate the association between depressive symptoms and self-rated health by sex among University students in France and Japan. METHODS: A cross-sectional study was conducted by using two large cohorts of students aged ≥18 years (n = 5655 in Bordeaux, France and n = 17,148 in Kyoto, Japan). Depressive symptoms (PHQ-2 scale), Likert scale of self-rated health, socio-demographic characteristics and health habits were collected through self-administered questionnaires. Multivariate logistic regression models were performed to describe the association between depressive symptoms and other variables including self-rated health, stratified by sex. RESULTS: A high score of PHQ-2 (high depressive symptoms) was associated with poor self-rated health in both cohorts independently of all other variables (OR 2.82, 95%CI 1.99-4.01 in France, OR 7.10, 95%CI 5.76-8.74 in Japan). Although the prevalence of depressive symptoms between sexes was different in French students (males 15.4%, females 25.0%, p < 0.001), it was similar in Japanese students (males 3.5%, females 3.3%, p = 0.466), who reported less depressive symptoms than French students. The association between depressive symptoms and poor self-rated health was greater in Japanese females (OR 12.40, 95%CI 7.74-20.00) than in males (OR 6.30, 95%CI 4.99-7.95), whereas the strength of the association was almost similar in French students (OR 2.17, 95%CI 0.86-5.47 in males, OR 2.98, 95%CI 2.03-4.38 in females). CONCLUSIONS: Depressive symptoms were associated with self-rated health among University students in both countries with slightly differences in sex. Self-rated health would be a simple, reliable and universal indicator for healthcare professionals and University staff to identify students at risk of depression.

Phase II study of S-1-based sequential combination chemotherapy including oxaliplatin plus bevacizumab and irinotecan with or without cetuximab for metastatic colorectal cancer: the SOBIC trial.

BACKGROUND: Fluorouracil and leucovorin combined with oxaliplatin or irinotecan plus bevacizumab (Bmab) or cetuximab (Cmab) are now widely accepted treatment options as first-line or second-line chemotherapy for metastatic colorectal cancer (mCRC). Sequential chemotherapy with oral 5-FU backbone for mCRC without using central venous ports is beneficial for both patients and physicians. We designed the SOBIC trial to validate the effectiveness of the first- and second-line oral combination chemotherapy for mCRC. PATIENTS AND METHODS: From May 2010 through March 2013, 52 patients were enrolled from 47 institutions in the Hyogo Colorectal Cancer Surgery Group. First-line chemotherapy was S-1 + oxaliplatin (SOX) plus Bmab, and second-line chemotherapy after first-line failure was irinotecan + S-1 (IRIS) + Cmab, IRIS + Bmab, or IRIS based on the KRAS status. RESULTS: The 50 finally included patients received first-line chemotherapy. Second-line therapy was administered to 20 patients (40%): 12 patients received IRIS + Cmab and 8 patients received IRIS + Bmab. The median follow-up period was 48.6 months (range 35-67 months). The median second progression-free survival was 24.2 months (95% confidence interval [CI] 17.7-35.2). The response rate after first- and second-line chemotherapy was 46.7% and 15%, respectively. The median overall survival was 35.2 months (95% CI: 27.8 to not reached). The main grade 3-4 adverse events were sensory neuropathy (18%) and fatigue (10%). There were no treatment-related deaths. CONCLUSION: Sequential S-1-based combination regimens including oxaliplatin, irinotecan, Bmab, and Cmab were beneficial for patients with mCRC.

Impact of Bystander Cardiopulmonary Resuscitation and Dispatcher Assistance on Survival After Out-of-Hospital Cardiac Arrest Among Adult Patients by Location of Arrest.

We investigated the impact of bystander-initiated cardiopulmonary resuscitation (CPR), dispatcher assistance (DA), and location of arrest on survival and outcomes after out-of-hospital cardiac arrest (OHCA).From a nationwide population-based registry of OHCA patients in Japan, we enrolled adult patients with bystander-witnessed OHCA of medical origin between 2013 and 2015. The primary outcome measure was a neurologically favorable outcome, defined by cerebral performance category 1 or 2. Multivariable logistic regression analysis was used to assess the effects of bystander CPR and DA by location of arrest. A total of 104,621 cases were included (15,984 bystander CPR without DA [15.3%], 40,087 bystander CPR with DA [38.3%], and 48,550 no bystander CPR [46.4%]). In public locations, both the bystander-CPR-with-DA group (22.9% [1,068/4,665]; adjusted odds ratio (AOR), 1.62; 95% confidence interval (CI), 1.43-1.85) and the bystander-CPR-without-DA group (25.8% [918/3,557]; AOR, 1.43; 95% CI, 1.24-1.65) had neurologically favorable outcomes compared with the no-bystander-CPR group (9.9% [610/6,133]). In residential locations, the AORs were 1.44 (95% CI, 1.22-1.70) in the bystander-CPR-without-DA group and 1.60 (95% CI, 1.45-1.77) in the bystander-CPR-with-DA group. However, in nursing homes, bystander CPR was not associated with improved outcomes of OHCA, regardless of the implementation of DA.Bystander CPR with or without DA had better outcomes after OHCA in residential and public locations but not in nursing homes.

Public-Access Defibrillation and Out-of-Hospital Cardiac Arrest in Japan.

BACKGROUND: Early defibrillation plays a key role in improving survival in patients with out-of-hospital cardiac arrests due to ventricular fibrillation (ventricular-fibrillation cardiac arrests), and the use of publicly accessible automated external defibrillators (AEDs) can help to reduce the time to defibrillation for such patients. However, the effect of dissemination of public-access AEDs for ventricular-fibrillation cardiac arrest at the population level has not been extensively investigated. METHODS: From a nationwide, prospective, population-based registry of patients with out-of-hospital cardiac arrest in Japan, we identified patients from 2005 through 2013 with bystander-witnessed ventricular-fibrillation arrests of presumed cardiac origin in whom resuscitation was attempted. The primary outcome measure was survival at 1 month with a favorable neurologic outcome (Cerebral Performance Category of 1 or 2, on a scale from 1 [good cerebral performance] to 5 [death or brain death]). The number of patients in whom survival with a favorable neurologic outcome was attributable to public-access defibrillation was estimated. RESULTS: Of 43,762 patients with bystander-witnessed ventricular-fibrillation arrests of cardiac origin, 4499 (10.3%) received public-access defibrillation. The percentage of patients receiving public-access defibrillation increased from 1.1% in 2005 to 16.5% in 2013 (P<0.001 for trend). The percentage of patients who were alive at 1 month with a favorable neurologic outcome was significantly higher with public-access defibrillation than without public-access defibrillation (38.5% vs. 18.2%; adjusted odds ratio after propensity-score matching, 1.99; 95% confidence interval, 1.80 to 2.19). The estimated number of survivors in whom survival with a favorable neurologic outcome was attributed to public-access defibrillation increased from 6 in 2005 to 201 in 2013 (P<0.001 for trend). CONCLUSIONS: In Japan, increased use of public-access defibrillation by bystanders was associated with an increase in the number of survivors with a favorable neurologic outcome after out-of-hospital ventricular-fibrillation cardiac arrest.