Search

Mina Fukuchi,1 Takanori Yasutake,2 Miho Matsumoto,2 Ryohei Mizuno,3 Koichiro Fujita,4 Yasuhiro Sasuga1 1Hachioji Center for Research & Development, B&S Corporation Co., Ltd., Hachoji-shi, Tokyo, Japan; 2Healthcare Systems Co., Ltd., Nagoya-shi, Aichi, Japan; 3B&S Corporation Co, Ltd., Tokyo, Japan; 4Tokyo Medical and Dental University, Tokyo, JapanCorrespondence: Yasuhiro SasugaHachioji Center for Research and Development, B&S Corporation Co., Ltd., 1-31-1 Nanakuni, Hachioji-Shi, Tokyo 192-0919, JapanTel +81 42-638-8915Fax +81 42-638-8916Email y-sasuga@bandscorp.jpObjective: For the general population, the intestinal microbiota and its environment, including its metabolites, are important not only for disease prevention but also for overall quality of life. A convenient method to monitor the intestinal environment is to measure levels of urinary 3-indoxyl sulfate (3-IS). This approach has been used for several years. This study aims to clarify the efficacy of a lactic acid bacteria (LAB) dietary supplement combined with multi-strain LAB-fermented soy milk (LEX) extract in healthy, adult women with high urinary 3-IS levels.Materials and Methods: Japanese women aged 30– 50 years with high urinary 3-IS levels and a tendency toward constipation were enrolled in this study. Each of them received 10 mL of a LEX-containing dietary supplement daily for 4 weeks. The primary outcome was changes in urinary 3-IS levels, and the secondary ones included the amount of defecation and more subjective symptoms of their physical condition, such as the Constipation Assessment Scale (CAS).Results: Thirty participants were enrolled, and all completed the study. Every participant showed a statistically significant improvement in their level of urinary 3-IS after ingesting the test article for 4 weeks. Any changes in urinary 3-IS also showed a high correlation to initial 3-IS levels. Moreover, CAS scores and other subjective symptoms improved after ingestion of the LEX-containing dietary supplement. The level of urinary 3-IS showed a modest degree of correlation with the score of overall physical condition, including CAS (Pearson’s r = 0.21; p < 0.05).Conclusion: These findings suggest that orally ingested LEX improves urinary 3-IS levels as an index of the health of the intestinal environment and that monitoring urinary 3-IS levels is effective in assessing changes in the intestinal environment and overall physical condition.Keywords: lactic acid bacteria, soybean, 3-indoxyl sulfate, intestinal environment, intestinal microbiota, postbiotics

Abstract Suppressor of mek1 (Dictyostelium) homolog 2 (Smek2), was identified as one of the responsible genes for diet-induced hypercholesterolemia (DIHC) of exogenously hypercholesterolemic (ExHC) rats. A deletion mutation in Smek2 leads to DIHC via impaired glycolysis in the livers of ExHC rats. The intracellular role of Smek2 remains obscure. We used microarrays to investigate Smek2 functions with ExHC and ExHC.BN-Dihc2 BN congenic rats that harbor a non-pathological Smek2 allele from Brown-Norway rats on an ExHC background. Microarray analysis revealed that Smek2 dysfunction leads to extremely low sarcosine dehydrogenase (Sardh) expression in the liver of ExHC rats. Sarcosine dehydrogenase demethylates sarcosine, a byproduct of homocysteine metabolism. The ExHC rats with dysfunctional Sardh developed hypersarcosinemia and homocysteinemia, a risk factor for atherosclerosis, with or without dietary cholesterol. The mRNA expression of Bhmt, a homocysteine metabolic enzyme and the hepatic content of betaine (trimethylglycine), a methyl donor for homocysteine methylation were low in ExHC rats. Results suggest that homocysteine metabolism rendered fragile by a shortage of betaine results in homocysteinemia, and that Smek2 dysfunction causes abnormalities in sarcosine and homocysteine metabolism.

Abstract In our previous study, enterohepatic 12α-hydroxylated (12α) bile acid (BA) levels were found to be correlated with hepatic triacylglycerol concentration in rats fed high-fat (HF) diet. Since BA composition is diverse depending on animal species, we evaluated whether such a relationship is applicable in mice in response to an HF diet. C57BL/6JJmsSLC (B6) male mice were fed HF diet for 13 weeks and analyzed for triacylglycerol, cholesterol, oxysterols, and other metabolites in the liver. The BA composition was determined in the liver, small intestinal contents, portal plasma, aortic plasma, and feces. Neutral sterols were also measured in the feces. The ratio of 12α BA/non-12 BA increased in the liver, portal plasma, small intestinal contents, and feces of HF-fed B6 mice. Moreover, a positive correlation was observed between the ratio of fecal 12α BAs/non-12 BAs and hepatic triacylglycerol concentration. The concentration of 7α-hydroxycholesterol was increased in the liver of HF-fed B6 mice, whereas no increase was observed in the hepatic expression of cytochrome P450 family 7 subfamily A member 1. The present study showed that the ratio of 12α BA/non-12 BA in feces is closely associated with hepatic triacylglycerol accumulation in B6 mice fed HF diet.

Abstract Background Frailty has been identified as a risk factor for cognitive impairment and dementia. However, it is not known whether familial factors, such as genetics and shared environmental factors, underlie this association. We analyzed the association between frailty and the risk of dementia in a large twin cohort and examined the role of familial factors in the association. Methods The Rockwood frailty index (FI) based on 44 health deficits was used to assess frailty. The population-level association between FI and the risk of all-cause dementia was analyzed in 41,550 participants of the Screening Across the Lifespan Twin (SALT) study (full sample, aged 41–97 years at baseline), using Cox and competing risk models. A subsample of 10,487 SALT participants aged 65 and older who received a cognitive assessment (cognitive sample) was used in a sensitivity analysis to assess the effect of baseline cognitive level on the FI-dementia association. To analyze the influence of familial effects on the FI-dementia association, a within-pair analysis was performed. The within-pair model was also used to assess whether the risk conferred by frailty varies by age at FI assessment. Results A total of 3183 individuals were diagnosed with dementia during the 19-year follow-up. A 10% increase in FI was associated with an increased risk of dementia (hazard ratio [HR] 1.17 (95% confidence interval [CI] 1.07, 1.18)) in the full sample adjusted for age, sex, education, and tobacco use. A significant association was likewise found in the cognitive sample, with an HR of 1.13 (95% CI 1.09, 1.20), adjusted for age, sex, and cognitive level at baseline. The associations were not attenuated when adjusted for APOE ɛ4 carrier status or considering the competing risk of death. After adjusting for familial effects, we found no evidence for statistically significant attenuation of the effect. The risk conferred by higher FI on dementia was constant after age 50 until very old age. Conclusions A higher level of frailty predicts the risk of dementia and the association appears independent of familial factors. Targeting frailty might thus contribute to preventing or delaying dementia.

Abstract Background Recurrence of atrial fibrillation (AF) after pulmonary vein isolation (PVI) is associated with left atrial (LA) remodeling; however, its association with right atrial (RA) remodeling remains unclear. Objective This study aimed to identify whether RA structural remodeling could predict recurrence of AF after PVI. Methods This study prospectively analyzed 245 patients with AF who had undergone PVI. RA and LA volumes were determined by contrast‐enhanced computed tomography. Atrial structural remodeling was defined as an atrial volume of ≥110 mL according to previous reports and receiver operating characteristic curve analysis. Results After excluding 32 patients, 213 patients were analyzed. During a follow‐up period of 12 months, 41 patients (19%) demonstrated atrial arrhythmia recurrence after PVI. With the Cox proportional‐hazards model, RA structural remodeling was the only predictor of arrhythmia recurrence (hazard ratio, 1.012; 95% confidence interval 1.003‐1.021; P = .009). Kaplan–Meier analysis showed that arrhythmia recurrence was more frequent in the RA structural remodeling group compared with the group without RA remodeling (log‐rank, P

Abstract We previously reported that dietary supplementation with cholic acid (CA), the primary 12α-hydroxylated (12αOH) bile acid (BA), reduces plasma adiponectin concentration in rats. The aim of this study was to examine the distribution of adiponectin in the body of CA-fed rats and its influence on mucosal immunoglobulin A concentration in the intestine. Rats were fed a diet supplemented with or without CA (0.5 g CA/kg diet) for 13 weeks. A reduction in plasma adiponectin level was observed from week 3. At the end of the experiment, the CA diet reduced plasma adiponectin concentration both in the portal and aortic plasma. Accumulation of adiponectin was accompanied by an increase in cadherin-13 mRNA expression in the ileal mucosa of CA-fed rats. No increase was observed in adiponectin mRNA expression in the ileal and adipose tissues of the CA-fed rats. Immunoglobulin A concentration in the ileal mucosa was elevated in the CA-fed rats and was correlated with the ileal adiponectin concentration. 12αOH BAs may modulate mucosal immune response that are involved in the accumulation of adiponectin in the ileum.

Abstract Background The physical and psychological health impacts on victims of the Great East Japan Earthquake (GEJE) have lasted for a long time. Some cross-sectional studies have reported a relationship between social networks and/or social support and mental health among victims. Previous studies were cross-sectional observations at one time point after a disaster, it remains unclear whether the lack of social trust soon after the GEJE predicts long-term mental health outcomes among the victims. The objective of the present study was to examine prospectively the association between social trust soon after the GEJE and trends in sleep disorders up to 6 years after the GEJE. Methods We conducted a health survey on residents living in two areas affected by the GEJE. We analyzed data from 1293 adults (aged ≥18 years) who had participated in an initial health survey. The participants responded to a self-administrated questionnaire composed of items on health condition, mental health, including sleep disorders (based on the Athens Insomnia Scale [AIS]), and social trust. We classified the participants into two categories (high or low) based on the level of social trust at the first health survey. A linear mixed model was used to estimate trends in AIS scores in relation to social trust at the first health survey. Results The AIS scores of participants in the low social trust group were significantly higher than those in the high social trust group throughout the 6 years after the GEJE (P

Abstract Background Inbred strains are characterized by less genetic variation, which suggests usefulness of inbred strains for evaluations of various parameters. In this study, experimental reproducibility in several parameters was compared between an outbred Wistar rat and Wistar King A Hokkaido (WKAH/HkmSlc) rat, the inbred strain that is originated from Wistar rats. Methods Difference of variations was investigated in parameters of body compositions and liver functions such as body weight, liver weight, liver triglycerides (TG), liver cholesterol and plasma alanine aminotransferase activity (ALT) between WKAH rats and outbred Wistar rats by using the coefficient of variation (CV). Results There was no difference in the CVs of body weight and relative liver weight between WKAH and Wistar rats. The CVs of body weight and relative liver weight were below 10% in both WKAH and Wistar rats. The CVs of TG, cholesterol, and ALT in Wistar rats were between 30 and 40%, whereas those in WKAH rats were between 10 and 25%. A low CV level of TG was observed in WKAH rats compared to that in Wistar rats regardless of the duration of the experimental period in those rat strains. Conclusion The low CV values in metabolic parameters involved in liver functions in the inbred rats suggested an advantage of using inbred rather than outbred rats for the evaluation of liver lipid metabolism.

Background: A growing number of epidemiology studies have shown that poor oral health is associated with an increased incidence of functional disability. However, there are few studies in which the confounding bias is adjusted appropriately. In this study, we examined whether dental status is associated with functional disability in elderly Japanese using a 13-year prospective cohort study after elimination of confounding factors with propensity score matching. Methods: Participants were community-dwelling Japanese aged 70 years or older who lived in the Tsurugaya district of Sendai (n = 838). The number of remaining teeth (over 20 teeth vs 0–19 teeth) was defined as the exposure variable. The outcome was the incidence of functional disability, defined as the first certification of long-term care insurance (LTCI) in Japan. The variables that were used to determine propensity score matching were age, sex, body mass index (BMI), medical history (stroke, hypertension, myocardial infarction, cancer, and diabetes), smoking, alcohol consumption, educational attainment, depression symptoms, cognitive impairment, physical function, social support, and marital status. Results: As a result of the propensity score matching, 574 participants were selected. Participants with 0–19 teeth were more likely to develop functional disability than those with 20 or more teeth (hazard ratio 1.33; 95% confidence interval, 1.01–1.75). Conclusions: In this prospective cohort study targeting community-dwelling older adults in Japan, having less than 20 teeth was confirmed to be an independent risk factor for functional disability even after conducting propensity score matching. This study supports previous publications showing that oral health is associated with functional disability.

A dietary symbiotic supplement of okara, a by-product of tofu manufacturing with Bacillus coagulans lilac-01 found to reduce secondary bile acid (BA) in a rat study and cholic acid (CA), a primary 12α-hydroxylated (12αOH) BA, induces lipid accumulation in rats. In this study, we investigated whether dietary supplementation of a synbiotic with okara and Bacillus coagulans lilac-01 improves CA-induced hepatic lipid accumulation. Male Wistar/ST rats (4 weeks old) were fed with or without CA-supplementation combined with the synbiotic for 2 weeks. The CA diet increased hepatic triglycerides and the synbiotic diet in combination with CA normalized liver triglyceride concentration accompanied by suppression of hepatic fatty acid synthase expression, enhancement of fecal triglyceride excretion, and increase in fecal non-12αOH BA excretion. Dietary supplementation with the okara synbiotic ameliorated hepatic lipid accumulation probably by reducing de novo lipogenesis and enhancing fecal triglyceride excretion.

Hereditary (variant) transthyretin amyloidosis (ATTRv amyloidosis), which is caused by variants in the transthyretin (TTR) gene, leads to TTR amyloid deposits in multiple organs and various symptoms such as limb ataxia, muscle weakness, and cardiac failure. Interaction between amyloid proteins and extracellular vesicles (EVs), which are secreted by various cells, is known to promote the clearance of the proteins, but it is unclear whether EVs are involved in the formation and deposition of TTR amyloid in ATTRv amyloidosis. To clarify the relationship between ATTRv amyloidosis and EVs, serum-derived EVs were analyzed. In this study, we showed that cell-derived EVs are involved in the formation of TTR amyloid deposits on the membrane of small EVs, as well as the deposition of TTR amyloid in cells. Human serum-derived small EVs also altered the degree of aggregation and deposition of TTR. Furthermore, the amount of TTR aggregates in serum-derived small EVs in patients with ATTRv amyloidosis was lower than that in healthy controls. These results indicate that EVs contribute to the metabolism of TTR amyloid, and suggest that TTR in serum-derived small EVs is a potential target for future ATTRv amyloidosis diagnosis and therapy.

Heart failure (HF) is challenging public medical and healthcare systems. This study aimed to develop and validate a novel deep learning-based prognostic model to predict the risk of all-cause mortality for patients with HF. We also compared the performance of the proposed model with those of classical deep learning- and traditional statistical-based models. The present study enrolled 730 patients with HF hospitalized at Toho University Ohashi Medical Center between April 2016 and March 2020. A recurrent neural network-based model (RNNSurv) involving time-varying covariates was developed and validated. The proposed RNNSurv showed better prediction performance than those of a deep feed-forward neural network-based model (referred as “DeepSurv”) and a multivariate Cox proportional hazard model in view of discrimination (C-index: 0.839 vs. 0.755 vs. 0.762, respectively), calibration (better fit with a 45-degree line), and ability of risk stratification, especially identifying patients with high risk of mortality. The proposed RNNSurv demonstrated an improved prediction performance in consideration of temporal information from time-varying covariates that could assist clinical decision-making. Additionally, this study found that significant risk and protective factors of mortality were specific to risk levels, highlighting the demand for an individual-specific clinical strategy instead of a uniform one for all patients.

Preoperative serum levels of sialyl Lewis(a) (CA 19-9), sialyl Lewis(x) (SLX), and sialyl Tn (STN) antigens in colorectal cancer patients were examined to establish predictive factors for serum levels of these antigens compared with carcinoembryonic antigen (CEA). A total of 308 patients who underwent resection for a colorectal cancer were divided into low and high antigen groups (higher or lower than a selected diagnostic-based cutoff value). The cutoff values were 37 U/ml for CA19-9, 38 U/ml for SLX, 45 U/ml for STN, and 2.5 ng/ml for CEA. The American Joint Committee on Cancer Classification and Stage grouping was used to classify the tumors. Statistical tests were conducted using univariate and multivariate logistic regression analyses. For CA19-9, 81 patients (26.3%) were assigned to the high antigen group: for SLX, 39 (12.7%); for STN, 33 (10.7%); and for CEA, 133 (43.2%). Multivariate logistic regression analysis revealed that predictive factors associated with high antigen levels were female sex (odds ratio [OR], 1.78 vs male sex), T4 (OR, 3.26 vs T1/T2), and M1 (OR, 3.35 vs M0) for CA19-9; M1 (OR, 6.40 vs M0) for SLX; mucinous carcinoma (OR, 8.45 vs well differentiated adenocarcinoma) and M1 (OR, 8.24 vs M0) for STN; and mucinous carcinoma (OR, 7.21 vs well differentiated adenocarcinoma), T3/T4 (OR, 3.84/4.18, respectively, vs T1/T2), and M1 (OR, 6.39 vs M0) for CEA. In conclusion, high serum levels of CA19-9, SLX, and STN are strongly associated with distant metastasis. In addition, high serum levels of CA19-9 may be an independent predictor for female gender and T4, and high serum levels of STN may be an independent predictor for mucinous carcinoma. [ABSTRACT FROM AUTHOR]

Abstract Background Although our previous study using a food frequency questionnaire simulated nutritional characteristics of the traditional Japanese diet, this issue has not been sufficiently evaluated. This study was conducted to examine the relationship between the traditional Japanese diet and nutrient density (ND). Methods A cross-sectional study employing the dietary record method was conducted among 2221 community-dwelling Japanese adults (40–88 years) living in Aichi Prefecture, Japan, in 2006–2008. Based on previous studies, a 9-component Japanese Diet Index (JDI) and a 12-component modified JDI (mJDI12) were defined. To develop a new weighted index, a multiple linear regression model was used to select food components which were significantly associated with an ND score (integrated by 11 nutrient components) from the mJDI12 and weight them. Correlation analyses were performed between JDI, mJDI12, the new weighted JDI score and the ND score and its 11 nutrient components. The findings were validated with data from 2008 to 2010 by assessing the associations between the JDIs scores and the ND score. Results Scores of the JDI and mJDI12 were positively correlated with the ND score (corresponding Spearman’s ρ [95% confidence interval; CI], 0.34 [0.31, 0.38] and 0.44 [0.41, 0.48], respectively; P

Background: Although lower household economic status is known to be a risk factor for obesity among school-age children, such an association among toddlers remains unclear. The present study investigated the association between household economic status and obesity in toddlers. Design: We conducted a cross-sectional study of children aged 4 years attending daycare centers in Japan. Information on subjective household economic status [“affluent”, “neither”, “less affluent”, or “non-affluent”] was collected via questionnaire from the children’s guardians in 2015. Based on measured values of height and weight, obesity was defined using the International Obesity Task Force cut-offs of overweight (BMI ≥17.47 for boys and ≥17.19 for girls). We used the logistic regression model to investigate the association between household economic status and obesity. Results: Among 1,848 respondents, the prevalence of obesity was 6.8%. Non-affluent household economic status was associated with a significantly higher probability of obesity in toddlers; the multivariate adjusted odds ratio for “non-affluent” households was 2.31 (95% confidence interval, 1.23–4.33) compared with “affluent” households. Conclusion: Perception of non-affluent economic status by the guardian was associated with a higher probability of toddler obesity. This result suggests that non-affluent household economic status is associated with obesity in toddlers.

Communication robots have been introduced in nursing care, education, and the hospitality sector. In the future, robots will be increasingly integrated into human society, with more opportunities to interact closely with humans. Therefore, investigating the symbiosis between humans and robots is critical. Touch, including actions, such as shaking hands, holding hands, and touching shoulders are common in most societies. These actions are called the social touch and are common modes of communication. Social touch not only conveys emotions and intentions but also mental and physical effects. Touch considerably influences social relationships: for example, by creating positive impressions and enabling the fulfillment of requests. Since the development of communication robots and other robots capable of physical contact, touch communication between humans and robots has been extensively studied. Although studies have revealed that touching a robot positively influences the impression regarding the robot and induces a relaxed feeling, negative perceptions related to trust on the robot have been reported. Thus, touch interactions between humans and robots are yet to be fully understood. Studies have focused on the effects of touch, such as touching the robot or being touched by the robot. Although interactions with robots that respond to touch, such as hugging behavior, have been studied, few studies have examined the psychological effects of robot responses to other types of touch such as hitting, stroking, and grasping. In this study, a humanoid robot was used to investigate how the reactive behavior exhibited by the robot in response to touch by a participant affects the degree of favorability and intellectual impression toward the robot as well as the sense of accomplishment regarding communication. Participants exhibited high favorability, feeling of relief, and willingness to continue the interaction with robots that exhibited appropriate reactions to the touch of participants. Participants exhibited a positive impression when they decided the touch gesture of the robot rather than when instructed on how to touch it. The results of this study can provide guidelines for improving the design and utilization of robots, such as therapeutic robots, that work alongside humans.

Objective To investigate the association between participation in government subsidies for domestic travel (subsidise up to 50% of all travel expenses) introduced nationally in Japan on 22 July 2020 and the incidence of symptoms indicative of COVID-19 infections.Design Cross-sectional analysis of nationally representative survey data.Setting Internet survey conducted between 25 August and 30 September 2020 in Japan. Sampling weights were used to calculate national estimates.Participants 25 482 survey respondents (50.3% (12 809) women; mean (SD) age, 48.8 (17.4) years).Main outcome measures Incidence rate of five symptoms indicative of the COVID-19 infection (high fever, sore throat, cough, headache, and smell and taste disorder) within the past month of the survey, after adjustment for characteristics of individuals and prefecture fixed effects (effectively comparing individuals living in the same prefecture).Results At the time of the survey, 3289 (12.9%) participated in the subsidy programme. After adjusting for potential confounders, we found that participants in the subsidy programme exhibited higher incidence of high fever (adjusted rate, 4.7% for participants vs 3.7% for non-participants; adjusted OR (aOR) 1.83; 95% CI 1.34 to 2.48; p

Identifying patient prognostic phenotypes facilitates precision medicine. This study aimed to explore phenotypes of patients with heart failure (HF) corresponding to prognostic condition (risk of mortality) and identify the phenotype of new patients by machine learning (ML). A unsupervised ML was applied to explore phenotypes of patients in a derivation dataset (n = 562) based on their medical records. Thereafter, supervised ML models were trained on the derivation dataset to classify these identified phenotypes. Then, the trained classifiers were further validated on an independent validation dataset (n = 168). Finally, Shapley additive explanations were used to interpret decision making of phenotype classification. Three patient phenotypes corresponding to stratified mortality risk (high, low, and intermediate) were identified. Kaplan–Meier survival curves among the three phenotypes had significant difference (pairwise comparison p < 0.05). Hazard ratio of all-cause mortality between patients in phenotype 1 (n = 91; high risk) and phenotype 3 (n = 329; intermediate risk) was 2.08 (95%CI 1.29–3.37, p = 0.003), and 0.26 (95%CI 0.11–0.61, p = 0.002) between phenotype 2 (n = 142; low risk) and phenotype 3. For phenotypes classification by random forest, AUCs of phenotypes 1, 2, and 3 were 0.736 ± 0.038, 0.815 ± 0.035, and 0.721 ± 0.03, respectively, slightly better than the decision tree. Then, the classifier effectively identified the phenotypes for new patients in the validation dataset with significant difference on survival curves and hazard ratios. Finally, age and creatinine clearance rate were identified as the top two most important predictors. ML could effectively identify patient prognostic phenotypes, facilitating reasonable management and treatment considering prognostic condition.