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Objectives: Metabolic syndrome (MS) is a significant health concern in the working-age population. Since 2008, Japan has mandated health insurers to implement Specific Health Checkups to identify individuals with MS and preliminary groups, making Specific Health Guidance (SHG) compulsory for these groups. People receiving SHG multiple times is increasing as it is conducted as an annual public program. Therefore, we evaluated the influence of a health guidance history on the effectiveness of subsequent guidance. Methods: Using data from 10,191 participants in the 2017 Motivational Health Guidance (a type of SHG involving a single session), this longitudinal study assessed the changes in health checkup findings from 2017 to 2018. Participants were categorized based on their previous year’s (2016) SHG eligibility and participation: Group 1 (n=3,903) met the 2016 SHG criteria and participated, Group 2 (n=2,305) met the criteria but did not participate, and Group 3 (n=3,983) had no MS risk factors and did not need to participate in the 2016 SHG. Results: The entire cohort and Groups 2 and 3 exhibited significant weight loss after 1 year. Group 1 showed a significant negative association, with a 3% (odds ratio [OR] 0.64; 95% confidence interval [CI], 0.55–0.75) and 5% body weight loss (OR 0.66; 95% CI, 0.54–0.81) than Group 3. Men in Group 1 showed a significant association with new-onset MS (OR 2.56; 95% CI, 1.93–3.40). Conclusions: The findings suggest that participants with a history of health guidance in the previous year may have low rates of achieving weight loss and a high incidence of new-onset MS after 1 year.

Abstract Juvenile loneliness is a risk factor for psychopathology in later life. Deprivation of early social experience due to peer rejection has a detrimental impact on emotional and cognitive brain function in adulthood. Accumulating evidence indicates that soy peptides have many positive effects on higher brain function in rodents and humans. However, the effects of soy peptide use on juvenile social isolation are unknown. Here, we demonstrated that soy peptides reduced the deterioration of behavioral and cellular functions resulting from juvenile socially-isolated rearing. We found that prolonged social isolation post-weaning in male C57BL/6J mice resulted in higher aggression and impulsivity and fear memory deficits at 7 weeks of age, and that these behavioral abnormalities, except impulsivity, were mitigated by ingestion of soy peptides. Furthermore, we found that daily intake of soy peptides caused upregulation of postsynaptic density 95 in the medial prefrontal cortex and phosphorylation of the cyclic adenosine monophosphate response element binding protein in the hippocampus of socially isolated mice, increased phosphorylation of the adenosine monophosphate-activated protein kinase in the hippocampus, and altered the microbiota composition. These results suggest that soy peptides have protective effects against juvenile social isolation-induced behavioral deficits via synaptic maturation and cellular functionalization.

Abstract “Yips” are involuntary movements that interfere with the automatic execution of sports movements. However, how the coordination among the various muscles necessary for sports movements is impaired in athletes with yips remains to be fully understood. This study aimed to assess whether muscle synergy analysis through non-negative matrix factorization (NMF) could identify impaired spatiotemporal muscle coordination in baseball players with throwing yips. Twenty-two college baseball players, including 12 with and 10 without yips symptoms participated in the study. Electromyographic activity was recorded from 13 ipsilateral upper extremity muscles during full-effort throwing. Muscle synergies were extracted through NMF. Cluster analysis was conducted to identify any common spatiotemporal patterns of muscle synergies in players with yips. Whether individual players with yips showed deviations in spatiotemporal patterns of muscle synergies compared with control players was also investigated. Four muscle synergies were extracted for each player, but none were specific to the yips group. However, a more detailed analysis of individual players revealed that two of the three players who presented dystonic symptoms during the experiment exhibited specific patterns that differed from those in control players. By contrast, each player whose symptoms were not reproduced during the experiment presented spatiotemporal patterns of muscle synergies similar to those of the control group. The results of this study indicate no common spatiotemporal pattern of muscle synergies specific to the yips group. Furthermore, these results suggest that the spatiotemporal pattern of muscle synergies in baseball throwing motion is not impaired in situations where symptoms are not reproduced even if the players have yips symptoms. However, muscle synergy analysis can identify the characteristics of muscle coordination of players who exhibit dystonic movements. These findings can be useful in developing personalized therapeutic strategies based on individual characteristics of yips symptoms.

Abstract 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).

Abstract 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

The motor imagery ability is closely related to an individual's motor performance in sports. However, whether motor imagery ability is diminished in athletes with yips, in whom motor performance is impaired, is unclear. Therefore, this cross-sectional study aimed to determine whether general motor imagery ability or vividness of motor imagery specific to throwing motion is impaired in baseball players with throwing yips. The study enrolled 114 college baseball players. They were classified into three groups: 33 players in the yips group, 26 in the recovered group (previously had yips symptoms but had resolved them), and 55 in the control group. They answered the revised version of the vividness of movement imagery questionnaire (VMIQ-2), which assesses general motor imagery ability. Furthermore, they completed a questionnaire that assesses both positive and negative motor imagery vividness specific to baseball throwing. In the former, they responded to their ability to vividly imagine accurately throwing a controlled ball, whereas in the latter, they responded to the vividness of their experience of negative motor imagery associated with baseball throwing, specifically the image of a wild throw. No significant difference in the VMIQ-2 was found among the three groups. While no significant difference in the vividness of positive motor imagery for ball throwing was found in either first-person visual or kinesthetic perspectives among the three groups, the yips group exhibited significantly higher vividness of negative motor imagery than the control group in both perspectives. These results indicate that negative motor imagery specific to baseball throwing may be associated with symptoms of yips. Therefore, interventions addressing psychological aspects, such as anxiety, which are potential causes of the generation of negative motor imagery, may be necessary to alleviate the symptoms of yips.

Abstract Background and Aim Post‐endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most serious adverse event of ERCP. Therefore, it is important to identify high‐risk patients who require prophylactic measures. The aim of this study was to develop a practical prediction model for PEP that identifies high‐risk patients. Methods Patients who underwent ERCP at three tertiary hospitals between April 2010 and September 2012 were enrolled. The dataset was divided into a training set (two centers) and validation set (one center). Using the training set, univariable and multivariable analyses were performed to identify predictive factors for PEP. We constructed a scoring system and evaluated reproducibility using the validation set. Results A total of 2719 ERCPs were analyzed. PEP developed in 133 cases (4.9%). Risk factors (adjusted odds ratios [OR]) in the training set were a history of PEP (OR: 4.2), intact papilla (OR: 2.4), difficult cannulation (OR: 1.9), pancreatic guidewire‐assisted biliary cannulation (OR: 2.2), pancreatic injection (OR: 2.1), pancreatic intraductal ultrasonography (IDUS)/sampling from the pancreatic duct (OR: 2.2), and biliary IDUS/sampling from the biliary tract (OR: 2.8). A scoring system was constructed using these seven clinical variables. The areas under the receiver‐operating characteristic curve of this model were 0.799 in the training set and 0.791 in the validation set. In the high‐risk group at a score of 3 or higher, the incidence of PEP was 13.4%, and all severe/fatal cases were in the high‐risk group. Conclusions This scoring system helps to predict each patient's risk and select preventive measures.

Background: There is a need for evidence-based medicine (EBM) education for laypersons. However, there are few materials or opportunities to learn EBM for Japanese laypersons. Objective: The aim of this study was to develop and test the usability of e-learning material on EBM for health-conscious laypersons in Japan. Methods: This study was conducted in two steps. First, content elements for the material were identified using purposive evaluation and a prototype of the e-learning material was developed. Following this, usability testing of the material was conducted. A questionnaire survey and qualitative semi-structured focus group interviews were conducted with health-conscious laypersons. Subsequently, the material was refined and finalized. Key Results: A total of 217 descriptions related to EBM were extracted from 12 materials and were integrated into 56 major elements. Each element was rated from the viewpoint of usefulness for laypersons and reviewed by four expert panelists, and finally 18 elements were confirmed, most of which were critical appraisal skills related to critical health literacy. For the usability testing after constructing the material, 25 laypersons participated, and 19 (76%) felt very/rather much interest in the contents of the material in the questionnaire. The results of five focus group interviews showed that the effectiveness of the e-learning material was influenced by the story and characters, and whether the contents of the material were consistent with interviewees' daily interests. Conclusions: The e-learning material on EBM was found to be of interest to health-conscious laypersons and appeared to be useful in participants' daily lives. This study successfully developed novel e-learning material on the essential components of EBM for laypersons in Japan. [HLRP: Health Literacy Research and Practice. 2022;6(4):e290–e299.] Plain Language Summary: This study developed and tested the usability of e-learning material to encourage health-conscious laypersons in Japan to learn the fundamentals of evidence-based medicine. Most of the contents of the material are related to critical health literacy. The usability testing showed that the material was of interest to non-health professionals and useful for dealing with health information in their daily lives.

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.

Abstract 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.

Abstract We aimed to investigate the association between serum lactate levels during cardiopulmonary resuscitation (CPR) and survival in patients with out-of-hospital cardiac arrest (OHCA). From the database of a multicenter registry on OHCA patients, we included adult nontraumatic OHCA patients transported to the hospital with ongoing CPR. Based on the serum lactate levels during CPR, the patients were divided into four quartiles: Q1 (≤ 10.6 mEq/L), Q2 (10.6–14.1 mEq/L), Q3 (14.1–18.0 mEq/L), and Q4 (> 18.0 mEq/L). The primary outcome was 1-month survival. Among 5226 eligible patients, the Q1 group had the highest 1-month survival (5.6% [74/1311]), followed by Q2 (3.6% [47/1316]), Q3 (1.7% [22/1292]), and Q4 (1.0% [13/1307]) groups. In the multivariable logistic regression analysis, the adjusted odds ratio of Q4 compared with Q1 for 1-month survival was 0.24 (95% CI 0.13–0.46). 1-month survival decreased in a stepwise manner as the quartiles increased (p for trend

Abstract Background There is limited information on the predictive accuracy of commonly used predictors, such as lactate, pH or serum potassium for the survival among out-of-hospital cardiac arrest (OHCA) patients with hypothermia. This study aimed to identify the predictive accuracy of these biomarkers for survival among OHCA patients with hypothermia. Methods In this retrospective analysis, we analyzed the data from a multicenter, prospective nationwide registry among OHCA patients transported to emergency departments in Japan (the JAAM-OHCA Registry). We included all adult (≥18 years) OHCA patients with hypothermia (≤32.0 °C) who were registered from June 2014 to December 2017 and whose blood test results on hospital arrival were recorded. We calculated the predictive accuracy of pH, lactate, and potassium for 1-month survival. Results Of the 34,754 patients in the JAAM-OHCA database, we included 754 patients from 66 hospitals. The 1-month survival was 5.8% (44/754). The areas under the curve of the predictors and 95% confidence interval were as follows: pH 0.829 [0.767–0.877] and lactate 0.843 [0.793–0.882]. On setting the cutoff points of 6.9 in pH and 120 mg/dL (13.3 mmol/L) in lactate, the predictors had a high sensitivity (lactate: 0.91; pH 0.91) and a low negative likelihood ratio (lactate: 0.14; pH 0.13), which are suitable to exclude survival to 1 month. Furthermore, in additional analysis that included only the patients with potassium values available, a cutoff point of 7.0 (mmol/L) for serum potassium had high sensitivity (0.96) and a low negative likelihood ratio (0.09). Conclusion This study indicated the predictive accuracy of serum lactate, pH, and potassium for 1-month survival among adult OHCA patients with hypothermia. These biomarkers may help define a more appropriate resuscitation strategy.

Abstract Background We aimed to identify the association of pH value in blood gas assessment with neurological outcome among out-of-hospital cardiac arrest (OHCA) patients treated by extracorporeal cardiopulmonary resuscitation (ECPR). Methods We retrospectively analyzed the database of a multicenter prospective observational study on OHCA patients in Osaka prefecture, Japan (CRITICAL study), from July 1, 2012 to December 31, 2016. We included adult OHCA patients treated by ECPR. Patients with OHCA from external causes such as trauma were excluded. We conducted logistic regression analysis to identify the odds ratio (OR) and 95% confidence interval (CI) of the pH value for 1 month favorable neurological outcome adjusted for potential confounders including sex, age, witnessed by bystander, CPR by bystander, pre-hospital initial cardiac rhythm, and cardiac rhythm on hospital arrival. Results Among the 9822 patients in the database, 260 patients were finally included in the analysis. The three groups were Tertile 1: pH ≥ 7.030, Tertile 2: pH 6.875–7.029, and Tertile 3: pH < 6.875. The adjusted OR of Tertiles 2 and 3 compared with Tertile 1 for 1 month favorable neurological outcome were 0.26 (95% CI 0.10–0.63) and 0.24 (95% CI 0.09–0.61), respectively. Conclusions This multi-institutional observational study showed that low pH value (< 7.03) before the implementation of ECPR was associated with 1 month unfavorable neurological outcome among OHCA patients treated with ECPR. It may be helpful to consider the candidate for ECPR.

Background: For effective screening in urinalysis, information on high-risk groups is needed; however, there is a lack of evidence in young adults in particular. The aim of this study was to provide information on urinalysis in young adults and to identify high-risk groups of urinalyses using multi-year data obtained from annual large-scale check-ups. Method: We used annual health check-up data collected from 2011 to 2016 at Kyoto University in Japan. Eligible participants were those aged 18–39 years who underwent annual health check-ups for four consecutive years between 2011 and 2016. We conducted descriptive analyses and calculated the risk ratios (RRs) for urinary abnormalities in the fourth year of urinalysis. Results: In total, 13,640 participants (10,877 men, 79.7%) met the eligibility criteria. The mean prevalence rates of proteinuria, haematuria and glucosuria were 1.61% (men: 1.63%; women: 1.53%), 1.48% (men: 0.53%; women: 5.22%) and 0.46% (men: 0.52%; women: 0.25%), respectively. Participants with urinary abnormalities at least once in the initial 3 years had a higher risk of urinary abnormalities in the fourth year than participants with no abnormal findings in the initial 3 years; the risk ratios (RRs) of proteinuria, haematuria and glucosuria were 3.5 (95% confidence interval (CI) = 3.2–3.7), 12.2 (95% CI = 11.7–12.7) and 42.6 (95% CI = 37.7–48.1), respectively. The RRs of all urinary abnormalities in the fourth year increased as the frequency of urinary abnormalities over the preceding 3 years increased. In haematuria, differences of the RR were observed between men and women. Conclusion: We clarified the prevalence of urinary abnormalities in young adults and high-risk groups of urinary abnormalities. Our findings support the need for multi-year annual urinalysis.

The triggers of initial onset of yips symptoms can be broadly divided into psychological and non-psychological factors; however, a trigger-based classification of yips has not been established. This study aims to obtain insight into the prevention of yips by clarifying whether there are differences in symptoms and personality traits according to a trigger-based classification of yips in baseball players. A total of 107 college baseball players responded to a questionnaire assessing the presence or absence of yips and its symptoms. They were classified into the psychologically triggered yips group, the non-psychologically triggered yips group, and the non-yips group based on the presence or absence of yips and the triggers of its initial onset. Additionally, we compared whether personality traits examined by the NEO Five-Factor Inventory differed across these three groups. The psychologically triggered yips group had significantly higher agreeableness scores compared with the non-yips group, whereas the non-psychologically triggered yips group had significantly higher neuroticism scores compared with the psychologically triggered yips group. In the non-psychologically triggered yips group, there was a significantly higher frequency of throwing errors than in the psychologically triggered yips group, with a tendency to develop yips symptoms gradually. Since the trigger-based classification of yips is closely related to the strength of the yips symptoms and the players' personality traits, the results of this study contribute to a better understanding of the symptoms of yips and establishment of the prevention of yips. Large prospective studies are necessary to determine the causal relationship between a trigger-based classification of yips and the personality traits and symptoms of athletes with yips.

Abstract Background Little is known about the associations between the duration of prehospital cardiopulmonary resuscitation (CPR) by emergency medical services (EMS) and outcomes among paediatric patients with out-of-hospital cardiac arrests (OHCAs). We investigated these associations and the optimal prehospital EMS CPR duration by the location of arrests. Methods We included paediatric patients aged 0–17 years with OHCAs before EMS arrival who were transported to medical institutions after resuscitation by bystanders or EMS personnel. We excluded paediatric OHCA patients for whom CPR was not performed, who had cardiac arrest after EMS arrival, whose EMS CPR duration were 30 min) in both groups (1.4% [6/417] in residential locations and 0.6% [1/170] in public locations). Conclusions A longer prehospital EMS CPR duration is independently associated with a lower proportion of patients with a favourable neurological outcome. The association between prehospital EMS CPR duration and neurological outcome differed significantly by location of arrests.

Abstract Background To let the early elderly live well, understanding how lifestyle and psychosocial factors related to a decline in competence in daily living is important. Methods We investigated the associations between lifestyle and psychosocial factors at age 64 years and a decline in the Tokyo Metropolitan Institute of Gerontology Index of Competence score of ≥ 2 points at age 70 years among the participants in comprehensive medical check-ups living in a city in Japan. Multivariable logistic regression analyses were performed separately for men and women. Results Of the 1113 eligible men and 1203 eligible women, 110 men and 80 women showed a deteriorated competence in daily living during the 6 years. In men, risk was increased with ≥ 2 nighttime awakenings (multivariable odds ratio [mOR] 2.14, 95% confidence interval [CI] 1.19–3.86) and living alone (mOR 4.68, 95% CI 1.22–18.0), whereas risk was significantly decreased with a medium or fast gait (mOR 0.37 and 0.21, 95% CI 0.21–0.67 and 0.08–0.58) and high academic achievement (mOR 0.32 and 0.43, 95% CI 0.19–0.53 and 0.25–0.72). In women, risk was decreased with high life satisfaction (mOR 0.39, 95% CI 0.16–0.91) and participation in community activities (mOR 0.50, 95% CI 0.29–0.86) but increased with depressive mood (mOR 1.86, 95% CI 1.09–3.18). Conclusion Living alone for men and low life satisfaction for women at age 64 years were markedly associated with the risk of a subsequent declining competence in daily living.

Lifestyle modification is the primary treatment strategy for obesity, hypertension, dyslipidemia, and hyperglycemia. Recently, the Japanese government designed a healthcare retreat program for persons with cardiovascular risk factors. However, the structure and effectiveness of this program has not been fully discussed.Employees of a company group with obesity and one or more other cardiovascular risk factors were enrolled in the study. The participants in the three-day retreat program were compared with those receiving a brochure-based advice for their subsequent changes in the annual health check-up data using the propensity score matching method.Among the 415 eligible employees, 220 underwent the intensive program and 195 received a brochure-based advice. In the propensity score-matched subjects, reduction in body weight (2.7 kg vs. 0.99 kg, p

Recent studies have lent support to the possibility that inflammation is associated with the pathology of schizophrenia. In the study of measurement of inflammatory mediators, which are markers of inflammation, elevated inflammatory cytokine levels in the brain and blood have been reported in patients with schizophrenia. Several postmortem brain studies have also reported changes in the expression of inflammatory cytokines. However, it is not clear how these elevated inflammatory cytokines interact with other inflammatory mediators, and their association with the pathology of schizophrenia. We comprehensively investigated the expression of 30 inflammatory mediators in the superior temporal gyrus (STG) of 24 patients with schizophrenia and 26 controls using a multiplex method. Overall, inflammatory mediator expression in the STG was mostly unchanged. However, the expression of interleukin (IL)1-α and interferon-gamma-inducible protein (IP)-10 was decreased [IL-1α, median (IQR), 0.51 (0.37–0.70) vs. 0.87 (0.47–1.23), p = 0.01; IP-10, 13.99 (8.00–36.64) vs. 30.29 (10.23–134.73), p = 0.05], whereas that of IFN-α was increased [2.34 (1.84–4.48) vs. 1.94 (1.39–2.36), p = 0.04] in schizophrenia, although these alterations did not remain significant after multiple testing. Clustering based on inflammatory mediator expression pattern and analysis of upstream transcription factors using pathway analysis revealed that the suppression of IL-1α and IP-10 protein expression may be induced by regulation of a common upstream pathway. Neuroinflammation is important in understanding the biology of schizophrenia. While neuroimaging has been previously used, direct observation to determine the expression of inflammatory mediators is necessary. In this study, we identified protein changes, previously unreported, using comprehensive protein analysis in STG. These results provide insight into post-inflammatory alternation in chronic schizophrenia.

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

IntroductionThe aim of this trial was to investigate whether a digital device that provides real-time visualized brushing instructions would contribute to the removal of dental plaque over usual brushing instructions.MethodsWe conducted a single-center, parallel-group, stratified permuted block randomized control trial with 1:1 allocation ratio. Eligibility criteria included people aged ≥ 18 years, and exclude people who met the following criteria: severely crowded teeth; using interdental cleaning implement; having external injury in the oral cavity, or stomatitis; having less than 20 teeth; using orthodontic apparatus; visited to a dental clinic; having the possibility of consulting a dental clinic; having a dental license; not owning a smartphone or tablet device; smoker; taken antibiotics; pregnant; an allergy to the staining fluid; and employee of Sunstar Inc. All participants received tooth brushing instructions using video materials and were randomly assigned to one of two groups for four weeks: (1) an intervention group who used the digital device, providing real-time visualized instructions by connection with a mobile application; and (2) a control group that used a digital device which only collected their brushing logs. The primary outcome was the change in 6-point method plaque control record (PCR) score of all teeth between baseline and week 4. The t-test was used to compare the two groups in accordance with intention-to-treat principles.ResultsAmong 118 enrolled individuals, 112 participants were eligible for our analyses. The mean of PCR score at week 4 was 45.05% in the intervention group and 49.65% in the control group, and the change of PCR score from baseline was -20.46% in the intervention group and -15.77% in the control group (p = 0.088, 95% confidence interval -0.70-10.07).ConclusionsA digital device providing real-time visualized brushing instructions may be effective for the removal of dental plaque.

Abstract Background The quality of cardiopulmonary resuscitation (CPR) performed by emergency medical services (EMS) personnel affects patient outcomes after cardiac arrest. A CPR feedback device with an accelerometer mounted on a defibrillator can monitor the motion of the patient’s sternum to display and record CPR quality in real time. To evaluate the utility of real-time feedback, debriefing, and retraining using a CPR feedback device outside of the hospital, an open-label, cluster randomized controlled trial will be conducted in five municipalities of Osaka Prefecture, Japan. Methods Each EMS station within a fire department will be randomly assigned to: 1) the treatment group with real-time feedback, debriefing, and retraining using the CPR feedback device (intervention group); or 2) the conventional treatment group without real-time feedback, debriefing, and retraining (control group). This trial will include 2850 to 3020 patients over about 4 years. The primary outcome of the trial is 1-month favorable neurological survival, defined as cerebral performance category scale score 1 or 2. Secondary outcomes are 1-month survival, survival to hospital discharge, return of spontaneous circulation, and quality of CPR including fraction, depth, tempo, and ventilation rate. Discussion The trial will assess whether treatment monitored by the CPR feedback device, which allows for real-time feedback, debriefing, and retraining using CPR quality data, outperforms conventional treatment without real-time feedback, debriefing, and retraining in terms of 1-month favorable neurological survival in cardiac arrest patients receiving CPR outside the hospital. Trial registration University Hospital Medical Information Network (UMIN) Clinical Trials Registry, UMIN000021431. Registered on 11 March 2016.

Background: Most studies of plasma adiponectin (APN) and mortality among community-dwelling elderly focus on cardiovascular disease, but data on the relationship between plasma APN and cancer mortality is exiguous. We investigated whether APN is associated with cancer mortality in community-dwelling elderly people. Methods: We conducted a case-cohort study within the New Integrated Suburban Seniority Investigation (NISSIN) Project using a randomly drawn sub-cohort of 697 subjects (351 men and 346 women; mean age 64.5 [standard deviation, 0.5] years) among whom we compared cases of all-cause death (n = 269) and cancer death (n = 149) during a mean follow-up duration of 10.8 (standard deviation, 3.7) years. Associations between APN and mortality were assessed using weighted Cox regression analyses. Results: We observed significant positive associations between the APN concentration and cancer death in the first and third APN tertiles compared with the second APN tertile (hazard ratio [HR]T1 vs T2, 1.67; 95% confidence interval [CI], 1.00–2.79 and HRT3 vs T2, 2.10; 95% CI, 1.30–3.40). Further adjustment for possible confounders attenuated the association (HRT1 vs T2, 1.63; 95% CI, 0.93–2.84 and HRT3 vs T2, 2.10; 95% CI, 1.26–3.50). A similar but weaker association was seen for all-cause mortality (multivariate HRT1 vs T2, 1.45; 95% CI, 0.95–2.21 and HRT3 vs T2, 1.51; 95% CI, 1.01–2.25). Conclusion: Plasma APN and cancer mortality have a significant relationship among community-dwelling elderly people, which warrants further study.

Abstract Background Youth in general and college life in particular are characterized by new educational, vocational, and interpersonal challenges, opportunities, and substantial stress. It is estimated that 30–50% of university students meet criteria for some mental disorder, especially depression, in any given year. The university has traditionally provided many channels to promote students’ mental health, but until now only a minority have sought such help, possibly owing to lack of time and/or to stigma related to mental illness. Smartphone-delivered cognitive behavioral therapy (CBT) shows promise for its accessibility and effectiveness. However, its most effective components and for whom it is more (or less) effective are not known. Methods/design Based on the multiphase optimization strategy framework, this study is a parallel-group, multicenter, open, fully factorial trial examining five smartphone-delivered CBT components (self-monitoring, cognitive restructuring, behavioral activation, assertion training, and problem solving) among university students with elevated distress, defined as scoring 5 or more on the Patient Health Questionnaire-9 (PHQ-9). The primary outcome is change in PHQ-9 scores from baseline to week 8. We will estimate specific efficacy of the five components and their interactions through the mixed-effects repeated-measures analysis and propose the most effective and efficacious combinations of components. Effect modification by selected baseline characteristics will be examined in exploratory analyses. Discussion The highly efficient experimental design will allow identification of the most effective components and the most efficient combinations thereof among the five components of smartphone CBT for university students. Pragmatically, the findings will help make the most efficacious CBT package accessible to a large number of distressed university students at reduced cost; theoretically, they will shed light on the underlying mechanisms of CBT and help further advance CBT for depression. Trial registration UMIN, CTR-000031307. Registered on February 14, 2018.

IntroductionAdverse events following the injection (AEFIs) of human papillomavirus vaccine (HPVv) among female adolescents are still a major public health concern.MethodsAccording to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension statement for systematic reviews incorporating network meta-analyses, all prospective randomised trials will be included. The primary outcome for adverse events is topical pain during the observation period.We will mainly search 17 electronic databases from January 2000 through September 2019 with suitable Medical Subject Headings and text words for PubMed. Two reviewers will independently check the reports at the title/abstract level and identify potentially applicable studies. Then we will obtain their full texts and decide whether to include them based on the same eligible criteria.We will compare HPVv with placebo, HPVv with adjuvant and HPVv with other vaccines. Interstudy heterogeneity, publication biases or small study effects will be evaluated using conventional meta-analysis methods. The consistency of the network will be checked using tests for local and global inconsistency and the side-splitting method. To address the heterogeneity of treatment effects among the studies, we will use the multivariable random effect model.Ethics and disseminationThis pairwise or network meta-analysis does not require ethics approval. The data used here are not individual nor private. We will be able to determine which component of the vaccine induces adverse events, especially topical pain. This systematic review with network meta-analysis will provide valid answers regarding AEFIs for HPVv.PROSPERO registration numberCRD42018109265

Abstract Smooth pursuit eye movements often show directional asymmetry in pursuit initiation or steady‐state pursuit in both humans and monkeys. It has been demonstrated that the initial part of smooth pursuit is driven by visual motion related signals in cortical areas. Parietal cortex such as middle temporal (MT) and medial superior temporal (MST) areas are known to be involved in visual motion perception as well as pursuit initiation. Therefore, the purpose of this study is to determine whether directional asymmetry in pursuit initiation is associated with visual motion perception. We used a step‐ramp paradigm to induce horizontal smooth pursuit eye movements and then tested visual motion reaction time (RT). Visual motion RT was measured to the visual motion stimuli that moved leftward or rightward, which is an important parameter of our sensory motor processing based on visual motion perception. Nineteen healthy male subjects participated in the study. We found that some of our subjects showed directional asymmetries in initial pursuit acceleration between the leftward and rightward directions, which were consistent with an asymmetric bias in visual motion RT. Therefore, our results suggest that asymmetric pursuit initiation is associated with, at least in part, a bias of visual motion perception. These results could be due to a common neuronal pathway involved in both pursuit initiation and visual motion RT.

Background Little is known about whether cardiopulmonary resuscitation (CPR) training can increase bystander CPR in the community or the appropriate target number of CPR trainings. Herein, we aimed to demonstrate community‐wide aggressive dissemination of CPR training and evaluate temporal trends in bystander CPR. Methods and Results We provided CPR training (45‐minute chest compression–only CPR plus automated external defibrillator use training or the conventional CPR training), targeting 16% of residents. All emergency medical service–treated out‐of‐hospital cardiac arrests of medical origin were included. Data on patients experiencing out‐of‐hospital cardiac arrest and bystander CPR quality were prospectively collected from September 2010 to December 2015. The primary outcome was the proportion of high‐quality bystander CPR. During the study period, 57 173 residents (14.7%) completed the chest compression–only CPR training and 32 423 (8.3%) completed conventional CPR training. The proportion of bystander CPR performed did not change (from 43.3% in 2010 to 42.0% in 2015; P for trend=0.915), but the proportion of high‐quality bystander CPR delivery increased from 11.7% in 2010 to 20.7% in 2015 (P for trend=0.015). The 1‐year increment was associated with high‐quality bystander CPR (adjusted odds ratio, 1.461; 95% CI, 1.055–2.024). Bystanders who previously experienced CPR training were 3.432 times (95% CI, 1.170–10.071) more likely to perform high‐quality CPR than those who did not. Conclusions We trained 23.0% of the residents in the medium‐sized city of Osaka, Japan, and demonstrated that the proportion of high‐quality CPR performed on the scene increased gradually, whereas that of bystander CPR delivered overall remained stable.

Objectives: Estimates of the numbers of patients with intractable diseases in Japan use data from nationwide epidemiological surveys under the assumption that the mean number of patients among hospitals that respond to the survey is equal to that among hospitals that do not respond ( "the assumption of no response bias" ). We examine the validity of this assumption. Methods: Data from nationwide epidemiological surveys of eosinophilic granulomatosis with polyangiitis (EGPA) and familial Mediterranean fever (FMF) were used. Information from initial questionnaires and from second surveys, of hospitals that did not respond to the initial surveys, were combined in a statistical model to estimate rates of response. Results: The proportion of hospitals that had patients with EGPA and FMF was higher among hospitals that responded to the initial survey than among those that responded to the second survey. The ratio of the response rate for hospitals without affected patients to that for those with affected patients was estimated to be 0.86 for EGPA and 0.90 for FMF. The ratio of the number of patients estimated under the assumption of no response bias to that based on the estimated ratio of response rate between in hospitals with and without affected patients was 1.11 for EGPA and 1.09 for FMF. Conclusions: The number of patients with EGPA and FMF estimated under the assumption of no response bias was only about 10% greater than the true number, suggesting that the assumption was almost completely valid.

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 [greater than or equal to]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.

Although associations between oral health and pneumonia have been reported in previous studies, particularly in the institutionalized elderly, few prospective studies have investigated the association between oral condition and pneumonia among community-dwelling people and whether the findings among inpatients or patients in nursing homes are applicable to the general population is still unclear. The oral bacteria propagated in the periodontal regions may drop into the lung and increase the risk of pneumonia. We, therefore, investigated the association of tooth loss with mortality from pneumonia in a cohort study of Japanese dentists. Members of the Japan Dental Association (JDA) participated in the LEMONADE (Longitudinal Evaluation of Multi-phasic, Odontological and Nutritional Associations in Dentists) Study. From 2001 to 2006, they completed a baseline questionnaire on lifestyle and health factors including the number of teeth lost (excluding third molars). We followed 19,775 participants (mean age ± standard deviation, 51.4 ± 11.7 years; 1,573 women [8.0%] and 18,202 men [92.0%]) for mortality from pneumonia (ICD-10, J12-J18). Mortality data were collected via the fraternal insurance program of the JDA. The hazard ratios (HRs) were estimated with adjustment for sex, age, body mass index, smoking status, physical activity and diabetes history. During the median follow-up period of 9.5 years, we documented 68 deaths from pneumonia. Participants who were edentulous at baseline were at significantly increased risk of mortality from pneumonia. The multivariable-adjusted HRs were 2.07 (95% confidence interval [CI], 1.09-3.95) for the edentulous and 1.60 (95% CI, 0.83-3.10) for loss of 15-27 teeth relative to loss of 0-14 teeth (trend p = 0.026). The HR per one tooth loss was also significant; 1.031 (95% CI, 1.004-1.060). In conclusion, a large number of teeth lost may indicate an increased risk of mortality from pneumonia in community-dwelling populations.

In this paper, collision-free guidance control of multiple small unmanned aerial vehicles (SUAVs) is designed. Collision avoidance of the SUAVs should be considered in the control system design for safe operation. Therefore, a guidance control system using a distributed model predictive control (DMPC) is proposed to realize the collision avoidance. A constraint for the relative position vector between the each UAV is considered in the design for efficient avoidance. Small multi-rotor helicopter is considered as controlled object, and the guidance control system is designed by using the translational model of the helicopter. DMPC is designed with three constraints, an input constraint, a state constraint, and a relative position vector constraint. An input constraint and a state constraint realize collision avoidance in input within the constant limits. If the moving path of the one helicopter is significantly affected by the moving path of other helicopter, the relative position vector constraint makes the helicopters exchange their relative position each other. By using these constraints, smooth collision avoidance is realized. The numerical simulation and flight experiment is conducted to verify the effectiveness of designed control system.

Expertise of registered dietitians (RDs) is important for health guidance but has been poorly evaluated. We evaluated the kind of RD expertise that would improve their skills.This study was a post-hoc analysis of our randomized controlled trial, which compared the weight change between participants using the web-based self-disclosure health support and those using the email health support. Healthy men and women aged 35-64 years with a body mass index (BMI) of > = 24.5 kg/m2 were recruited for this study. We evaluated the relationship of RD expertise indicators including the duration of working as an RD, the experience of health counseling, and membership in the Japan Dietetic Association (JDA) with the weight loss of study participants. The primary endpoint was the change in body weight. Comparison of changes in body weight by the RD expertise indicators was evaluated using analysis of covariance.A total of 175 participants were eligible for analyses. Changes in body weight were significantly greater when they were supported by the RDs in the routine counseling group than when supported by the RDs in the non-routine counseling group (-1.8 kg versus -0.4 kg, fully adjusted P = 0.0089). Duration of working as an RD and JDA membership did not significantly affect changes in body weight.Among some indices of RD experience, the experience of providing routine experience of health counseling was associated with weight loss.

Micro-hole drilling of engineering ceramics has potential for application to fuel injection nozzles and fiber spinning nozzles, etc. To date among engineering ceramics, less study has been reported on the micro-hole drilling of silicon nitride. We therefore conducted micro-hole drilling of hot-pressed silicon nitride using a chemical vapor deposition (CVD) diamond-coated tool with ethanol as the cutting fluid. As a result, the successful drilling of silicon nitride was achieved with a smooth drilled surface and sufficient accuracy of the hole size. Wear damage of the CVD coated diamond tool and drilling debris of silicon nitride were investigated using scanning electron microscopy (SEM) with energy-dispersive X-ray spectroscopy (EDX). As a result, it is suggested that tribochemical reaction of silicon nitride effectively contributed to the micro-hole drilling characteristics; that is, smoother hole surface was obtained due to the polishing action of wear debris and tribochemical reaction products. The hole inlet size, varied during successive drilling process, could be explained in relation to the wear damage of the diamond-coated drill tip.

In this study, we design an autonomous navigation, guidance and control system for a small electric helicopter. Only small, light-weight, and inaccurate sensors can be used for the control of small helicopters because of the payload limitation. To overcome the problem of inaccurate sensors, a composite navigation system is designed. The designed navigation system enables us to precisely obtain the position and velocity of the helicopter. A guidance and control system is designed for stabilizing the helicopter at an arbitrary point in three-dimensional space. In particular, a novel and simple guidance system is designed using the combination of optimal control theory and quaternion kinematics. The designs of the study are validated experimentally, and the experimental results verify the efficiency of our navigation, guidance and control system for a small electric helicopter.

BACKGROUND: In March 2007, a regulatory advisory was issued in Japan to restrict oseltamivir use in children aged 10-19 years because of safety concerns over abnormal behavior. The effectiveness and validity of regulatory risk minimization actions remain to be reviewed, despite their significant public health implications. To assess the impact of the regulatory actions on prescribing practices and safety reporting. METHODOLOY/PRINICPAL FINDINGS: In this retrospective review of a nationwide pharmacy database, we analyzed 100,344 dispensation records for oseltamivir and zanamivir for the period from November 2006 to March 2009. The time trend in dispensations for these antiviral agents was presented before and after the regulatory actions, contrasted with intensity of media coverage and the numbers of spontaneous adverse reaction reports with regard to antivirals. The 2007 regulatory actions, together with its intense media coverage, reduced oseltamivir dispensation in targeted patients in fiscal year 2008 to 20.4% of that in fiscal year 2006, although influenza activities were comparable between these fiscal years. In contrast, zanamivir dispensation increased approximately nine-fold across all age groups. The number of abnormal behavior reports associated with oseltamivir in children aged 10-19 years decreased from fiscal year 2006 to 2008 (24 to 9 cases); this decline was offset by the increased number of reports of abnormal behavior in children under age 10 (12 to 28 cases). The number of reports associated with zanamivir increased in proportion to increased dispensation of this drug (11 to 114 cases). CONCLUSIONS/SIGNIFICANCE: The 2007 actions effectively reduced oseltamivir prescriptions and the number of reports of abnormal behavior in the targeted group. The observed increase in abnormal behavior reports in oseltamivir patients under age 10 and in zanamivir patients suggests that these patient groups may also be at risk, calling into question the validity of the current discrimination by age and agent (Abstract translation is available in Japanese: Appendix S1).

BACKGROUND: Dyskinesias are some of the major motor complications that impair quality of life for patients with Parkinson's disease. The purpose of the present study was to investigate the efficacy of amantadine in Parkinson's disease patients suffering from dyskinesias. METHODS: In this multi-center, double-blind, randomized, placebo-controlled, cross-over trial, 36 patients with Parkinson's disease and dyskinesias were randomized, and 62 interventions, which included amantadine (300 mg/day) or placebo treatment for 27 days, were analyzed. At 15 days after washout, the treatments were crossed over. The primary outcome measure was the changes in the Rush Dyskinesia Rating Scale (RDRS) during each treatment period. The secondary outcome measures were changes in the Unified Parkinson's Disease Rating Scale part IVa (UPDRS-IVa, dyskinesias), part IVb (motor fluctuations), and part III (motor function). RESULTS: RDRS improved in 64% and 16% of patients treated with amantadine or placebo, respectively, with significant differences between treatments. The adjusted odds-ratio for improvement by amantadine was 6.7 (95% confidence interval, 1.4 to 31.5). UPDRS-IVa was improved to a significantly greater degree in amantadine-treated patients [mean (SD) of 1.83 (1.56)] compared with placebo-treated patients [0.03 (1.51)]. However, there were no significant effects on UPDRS-IVb or III scores. CONCLUSIONS: Results from the present study demonstrated that amantadine exhibited efficacious effects against dyskinesias in 60-70% of patients. TRIAL REGISTRATION: UMIN Clinical Trial Registry UMIN000000780.

Objective: The aim of the study is to predict employees' long-term sick leave due to psychiatric disorders using the national psychological stress screening program. Methods: University employees who took long-term psychiatric sick leave in 2016-2018 were assigned as cases. Those who were present at work and matched for sex, age, and occupation type were assigned as controls. Answers in a 57-item questionnaire were analyzed by multivariable regression, and a prediction model was developed. It was validated in cases and matched controls in 2019. Results: Six items were identified as independent predictors by multivariable regression and included in a prediction model. The area under the receiver-operating characteristics curve was 0.768 (95% confidence interval: 0.723-0.813). This finding was similar to that in the validation sample. Conclusions: The performance of the prediction model was modest and the national Stress Check Program should be further refined. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]