Alcohol consumption and the risk of heart failure: the Suita Study and meta-analysis of prospective cohort studies.

BACKGROUND: Alcohol consumption is a modifiable lifestyle, but its role in heart failure (HF) development is controversial. Herein, we investigated the prospective association between alcohol consumption and HF risk. METHODS: A total of 2,712 participants (1,149 men and 1,563 women) from the Suita Study were followed up every two years. Cox regression was applied to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of HF risk for heavy drinking (≥46 g/day in men or ≥23 g/day in women) and never drinking compared to light drinking (<23 g/day in men or <11.5 g/day in women). Then, we combined the results of the Suita Study with those from other eligible prospective cohort studies in a meta-analysis using the random-effects model. RESULTS: In the Suita Study, within a median follow-up period of 8 years, 319 HF cases (162 in men and 157 in women) were detected. In men, but not women, never and heavy drinking carried a higher risk of HF than light drinking: HRs (95% CIs) = 1.65 (1.00, 2.73) and 2.14 (1.26, 3.66), respectively. Alike, the meta-analysis showed a higher risk of HF among heavy drinkers: HR (95% CI) = 1.37 (1.15, 1.62) and abstainers: HR (95% CI) = 1.18 (1.02, 1.37). CONCLUSION: We indicated a J-shaped association between alcohol consumption and HF risk among Japanese men. The results of the meta-analysis came in line with the Suita Study. Heavy-drinking men should be targeted for lifestyle modification interventions.

MLAGO: machine learning-aided global optimization for Michaelis constant estimation of kinetic modeling.

BACKGROUND: Kinetic modeling is a powerful tool for understanding the dynamic behavior of biochemical systems. For kinetic modeling, determination of a number of kinetic parameters, such as the Michaelis constant (Km), is necessary, and global optimization algorithms have long been used for parameter estimation. However, the conventional global optimization approach has three problems: (i) It is computationally demanding. (ii) It often yields unrealistic parameter values because it simply seeks a better model fitting to experimentally observed behaviors. (iii) It has difficulty in identifying a unique solution because multiple parameter sets can allow a kinetic model to fit experimental data equally well (the non-identifiability problem). RESULTS: To solve these problems, we propose the Machine Learning-Aided Global Optimization (MLAGO) method for Km estimation of kinetic modeling. First, we use a machine learning-based Km predictor based only on three factors: EC number, KEGG Compound ID, and Organism ID, then conduct a constrained global optimization-based parameter estimation by using the machine learning-predicted Km values as the reference values. The machine learning model achieved relatively good prediction scores: RMSE = 0.795 and R2 = 0.536, making the subsequent global optimization easy and practical. The MLAGO approach reduced the error between simulation and experimental data while keeping Km values close to the machine learning-predicted values. As a result, the MLAGO approach successfully estimated Km values with less computational cost than the conventional method. Moreover, the MLAGO approach uniquely estimated Km values, which were close to the measured values. CONCLUSIONS: MLAGO overcomes the major problems in parameter estimation, accelerates kinetic modeling, and thus ultimately leads to better understanding of complex cellular systems. The web application for our machine learning-based Km predictor is accessible at https://sites.google.com/view/kazuhiro-maeda/software-tools-web-apps , which helps modelers perform MLAGO on their own parameter estimation tasks.

Developing a Stroke Risk Prediction Model Using Cardiovascular Risk Factors: The Suita Study.

INTRODUCTION: Stroke remains a major cause of death and disability in Japan and worldwide. Detecting individuals at high risk for stroke to apply preventive approaches is recommended. This study aimed to develop a stroke risk prediction model among urban Japanese using cardiovascular risk factors. METHODS: We followed 6,641 participants aged 30-79 years with neither a history of stroke nor coronary heart disease. The Cox proportional hazard model estimated the risk of stroke incidence adjusted for potential confounders at the baseline survey. The model's performance was assessed using the receiver operating characteristic curve and the Hosmer-Lemeshow statistics. The internal validity of the risk model was tested using derivation and validation samples. Regression coefficients were used for score calculation. RESULTS: During a median follow-up duration of 17.1 years, 372 participants developed stroke. A risk model including older age, current smoking, increased blood pressure, impaired fasting blood glucose and diabetes, chronic kidney disease, and atrial fibrillation predicted stroke incidence with an area under the curve = 0.76 and p value of the goodness of fit = 0.21. This risk model was shown to be internally valid (p value of the goodness of fit in the validation sample = 0.64). On a risk score from 0 to 26, the incidence of stroke for the categories 0-5, 6-7, 8-9, 10-11, 12-13, 14-15, and 16-26 was 1.1%, 2.1%, 5.4%, 8.2%, 9.0%, 13.5%, and 18.6%, respectively. CONCLUSION: We developed a new stroke risk model for the urban general population in Japan. Further research to determine the clinical practicality of this model is required.

Playing a musical instrument and the risk of dementia among older adults: a systematic review and meta-analysis of prospective cohort studies.

BACKGROUND: Engaging in leisure activities was suggested to protect older adults from dementia. However, the association between playing a musical instrument and the risk of dementia is not well-established. This study aimed to investigate this association in older adults using a systematic review and meta-analysis of prospective cohort studies. METHODS: Pooled hazard ratio (HR) and 95% confidence interval (CI) of having dementia for older adults playing a musical instrument were calculated using the random-effects model. We performed the I2 statistic to detect heterogeneity across studies and the test for funnel plot asymmetry to assess publication bias. The risk of bias assessment was conducted using the modified Newcastle-Ottawa Scale. RESULTS: A total of three prospective cohort studies were found eligible: two from the U.S. and one from Japan. Playing a musical instrument, in the meta-analysis, was significantly associated with a decreased risk of dementia (HR = 0.64; 95% CI: 0.41, 0.98) among older adults. No signs of significant heterogeneity across studies (I2 = 23.3% and p-heterogeneity = 0.27) or publication bias (z= -1.3 and p-publication bias = 0.18) were identified. CONCLUSION: Playing a musical instrument was associated with a decreased risk of dementia among older adults. Older adults should be encouraged to engage in leisure activities, especially playing musical instruments.

Association Between White Blood Cell Count and Atrial Fibrillation Risk　- A Population-Based Prospective Cohort Study.

BACKGROUND: The incidence and prevalence of atrial fibrillation (AF) are increasing. The white blood cell (WBC) count is an indicator of systemic inflammation and is related to increased cardiovascular disease risk. Using data from the Suita Study, we investigated the association between WBC count and AF risk in the general Japanese population.Methods and Results: This prospective cohort study included 6,884 people, aged 30-84 years, with no baseline AF. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for AF incidence by WBC count quintile. Within a median follow-up period of 14.6 years, 312 AF cases were diagnosed. Compared with the lowest WBC count quintile, the highest quintile was associated with an increased AF risk (HR 1.57; 95% CI 1.07-2.29). The association was more pronounced among women than men (HR 2.16 [95% CI 1.10-4.26] and 1.55 [95% CI 0.99-2.44], respectively; P interaction=0.07), and among current than non-smokers (HR 4.66 [95% CI 1.89-11.50] and 1.61 [95% CI 1.01-2.57], respectively; P interaction=0.20). For each 1.0×109-cells/L increment in WBC count, AF risk increased by 9% in men (9% in non-smokers, 10% in current smokers) and 20% in women (13% in non-smokers, 32% in current smokers). CONCLUSIONS: A higher WBC count was positively associated with an elevated AF risk in the general Japanese population, especially in women who smoked.

The Lifelong Health Support 10: a Japanese prescription for a long and healthy life.

BACKGROUND: Although the age-adjusted incidence and mortality of cancer and cardiovascular disease (CVD) have been decreasing steadily in Japan, both diseases remain major contributors to morbidity and mortality along with the aging society. Herein, we aim to provide a prescription of 10 health tips for long and healthy life named the "Lifelong Health Support 10 (LHS10)." METHOD: The LHS10 was developed by the preventive medicine specialists at the National Cerebral and Cardiovascular Center in Suita, where it has been used for health guidance to prevent CVD, cancer, and cognitive decline in addition to their major risk factors such as hypertension, diabetes, and obesity. It consisted of the lifestyle modification recommendations of the 2014 Japanese Society of Hypertension guidelines and the 2017 Japan Atherosclerosis Society Guidelines for preventing atherosclerotic CVD. Further, it came in line with other international lifestyle modification guidelines. In this narrative review, we summarized the results of several Japanese epidemiological studies investigating the association between the LHS10 items and the risk of cancer, CVD, and other chronic diseases including dementia, diabetes, and chronic kidney disease. RESULTS: The LHS10 included avoiding smoking and secondhand smoke exposure, engaging in physical activity, refraining from excessive alcohol drinking, reducing fried foods and sugary soft drinks, cutting salt in food, consuming more vegetables, fruits, fish, soy foods, and fibers, and maintaining proper body weight. All items of the LHS10 were shown to reduce the risk of cancer, CVD, and other chronic diseases. CONCLUSIONS: The LHS10 can be a helpful tool for health guidance.

Stair climbing and incident atrial fibrillation: a prospective cohort study.

BACKGROUND: A protective role for physical activity against the development of atrial fibrillation (AF) has been suggested. Stair climbing is a readily available form of physical activity that many people practice. Herein, we investigated the association between stair climbing and the risk of AF in a Japanese population. METHODS: In this prospective cohort study, we used data of 6,575 people registered in the Suita Study, aged 30-84 years, and had no history of AF. The frequency of stair climbing was assessed by a baseline questionnaire, while AF was diagnosed during the follow-up using a 12-lead ECG, health records, check-ups, and death certificates. We used the Cox regression to calculate the hazard ratios and 95% confidence intervals of AF incidence for climbing stairs in 20-39%, 40-59%, and ≥60% compared with <20% of the time. RESULTS: Within 91,389 person-years of follow-up, 295 participants developed AF. The incidence of AF was distributed across the stair climbing groups <20%, 20-39%, 40-59%, and ≥60% as follows: 3.57, 3.27, 3.46, and 2.63/1,000 person-years, respectively. Stair climbing ≥60% of the time was associated with a reduced risk of AF after adjustment for age and sex 0.69 (0.49, 0.96). Further adjustment for lifestyle and medical history did not affect the results 0.69 (0.49, 0.98). CONCLUSION: Frequent stair climbing could protect from AF. From a preventive point of view, stair climbing could be a simple way to reduce AF risk at the population level.

Validity of DMIST for monitoring healing of diabetic foot ulcers.

A new diabetic foot evaluation scale was proposed, using the seven domains of depth, maceration, inflammation/infection, size, tissue type of the wound bed, type of wound edge, and tunneling/undermining. This scale was named "DMIST" as an acronym from the initials of the domains. The purpose of this study was to evaluate the validity of DMIST. Secondary analysis was conducted in three investigations performed using the diabetic foot ulcer assessment scale (DFUAS) in Japan and Indonesia. Secondary analysis was assessed using DMIST, PUSH, and DESIGN for 4 weeks based on DFUAS score and photographs of diabetic foot ulcers by researchers. Concurrent validity was determined from the correlation of total DMIST scores with PUSH and DESIGN scores. Construct validity was determined by comparisons between total DMIST score and grade of the Wagner classification. Predictive validity was determined by receiver operating characteristic curve analysis for wound non-healing 4 weeks later. Subjects comprised 35 Japanese patients and 118 Indonesian patients. Correlations of total DMIST score with PUSH and DESIGN scores were 0.831 and 0.822, respectively. Comparison of total DMIST scores with grade of the Wagner classification (Grade I vs. Grade II/III vs. Grade IV/V) was p < 0.001. Based on an area under the curve of 0.872, a DMIST score of 9 was selected as a cut-off, offering sensitivity of 0.855 and specificity of 0.786 for wound non-healing 4 weeks later. Our findings suggest that DMIST offers high validity.

Differences in the working pattern among wound, ostomy, and continence nurses with and without conducting the specified medical act: a multicenter time and motion study.

BACKGROUND: To overcome the shortage of medical care delivery in the rapidly aging Japanese society, the Ministry of Health, Labour and Welfare in 2010 started to train the nurses to be able to conduct the specified medical acts. The Japanese Nursing Association conducted the educational program to train the wound, ostomy, and continence nurses for the specified medical act of wound care. However, the difference between wound, ostomy, and continence nurses who conducted the medical act and those who did not was not clear. The aim of this study was to determine how trained wound, ostomy, and continence nurses spend their time during their entire shift in an acute hospital setting. METHODS: In this prospective observational study, we selected those wound, ostomy, and continence nurses who received advanced training in the wound management program (T-WN) in 2011-2012. Wound, ostomy, and continence nurses who did not receive the training (N-WN) were also recruited as controls. We conducted a time and motion study during subject's day shifts for 1 week. We calculated the time spent on tasks based on a task classification code that was created to facilitate a two-group comparison. RESULTS: Six T-WNs and five N-WNs were our analysis subjects. T-WNs spent significantly more time on direct care than did N-WNs (p = 0.00). Moreover, in the sub-categories s of direct care, T-WN spent significantly more time on "treatment" than did N-WN (p = 0.01). T-WN spent significantly more time on treatment with (p = 0.03) or without (p = 0.01) physicians than did N-WN. In the treatment activities, T-WN performed significantly more time on foot care (p = 0.01), wound cleansing (p = 0.01) and conservative sharp wound debridement (p = 0.01) than did N-WN. Frequencies of direct care interventions for the patients was significantly different between T-WN and N-WN (p = 0.04). CONCLUSIONS: T-WNs frequently engaged in direct care provided treatment for patients with chronic wounds.

Hypertensive disorders of pregnancy and the risk of dementia: a systematic review and meta-analysis of cohort studies.

This study aimed to investigate the association between hypertensive disorders of pregnancy (HDP) and subsequent risk of dementia using a systematic review and meta-analysis of cohort studies. We searched PubMed and Scopus for eligible studies that investigated the association between HDP and dementia risk. Using the random-effects model, pooled hazard ratio (HR) and 95% confidence interval (CI) of dementia risk in women with HDP were calculated. We applied the I2 statistic to measure heterogeneity across studies and the test for funnel plot asymmetry to evaluate publication bias. Six cohort studies were eligible: three from the United States, two from Sweden, and one from Denmark. When combined, HDP was associated with the risk of dementia: pooled HR (95% CI) = 1.31 (1.12, 1.53). The heterogeneity across studies was moderate (I2 = 47.3%, p-heterogeneity = 0.091), but no signs of publication bias were detected. The association of HDP with vascular dementia was stronger than that with Alzheimer's disease: pooled HRs (95% CIs) = 1.66 (1.13, 2.43) and 1.29 (0.97, 1.72), respectively. In conclusion, HDP was associated with a higher risk of dementia and this association was more prominent with vascular dementia.

Serum cholesterol levels and the risk of brain natriuretic peptide-diagnosed heart failure in postmenopausal women: a population-based prospective cohort study.

OBJECTIVE: Hormonal changes during menopause can disturb serum cholesterol which is closely associated with cardiovascular disease. This study investigated the prospective association between serum cholesterol and heart failure (HF) risk in postmenopausal women. METHODS: We analyzed data from 1,307 Japanese women, aged 55 to 94 years. All women had no history of HF, and their baseline brain natriuretic peptide (BNP) levels were less than 100 pg/mL. During the follow-ups conducted every 2 years, HF was diagnosed among women who developed BNP of 100 pg/mL or greater. Cox proportional hazard models were applied to calculate hazard ratios and 95% CI of HF for women per their baseline total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) levels. The Cox regression models were adjusted for age, body mass index, smoking, alcohol drinking, hypertension, diabetes, cardiac murmurs, arrhythmia, stroke or ischemic heart disease, chronic kidney disease, and lipid-lowering agent use. RESULTS: Within an 8-year median follow-up, 153 participants developed HF. In the multivariable-adjusted model, women with total cholesterol of 240 mg/dL or greater (compared with 160-199 mg/dL) and HDL-C of 100 mg/dL or greater (compared with 50-59 mg/dL) showed an increased risk of HF: hazard ratios (95% CI) = 1.70 (1.04-2.77) and 2.70 (1.10-6.64), respectively. The results remained significant after further adjusting for baseline BNP. No associations were observed with low-density lipoprotein cholesterol. CONCLUSIONS: Total cholesterol of 240 mg/dL or greater and HDL-C of 100 mg/dL or greater were positively associated with the risk of HF in postmenopausal Japanese women.

Prevalence of family history of cancer in the NC-CCAPH consortium of Japan.

The objective of this study was to identify the prevalence of family history of cancer using cohorts participating in the Japanese National Center Cohort Collaborative for Advancing Population Health (NC-CCAPH). We pooled data from seven eligible cohorts of the Collaborative with available data on family history of cancer. Prevalence of family history of cancer and corresponding 95% confidence intervals are presented for all cancers and selected site-specific cancers for the total population and stratified by sex, age, and birth cohort. Prevalence of family history of cancer increased with age ranging from 10.51% in the 15 to 39 year age category to 47.11% in 70-year-olds. Overall prevalence increased in birth cohorts from ≤ 1929 until 1960 and decreased for the next two decades. Gastric cancer (11.97%) was the most common site recorded for family members, followed by colorectal and lung (5.75%), prostate (4.37%), breast (3.43%) and liver (3.05%) cancer. Women consistently had a higher prevalence of family history of cancer (34.32%) versus men (28.75%). Almost one in three participants had a family history of cancer in this Japanese consortium study highlighting the importance of early and targeted cancer screening services.

Sleep duration and atrial fibrillation risk in the context of predictive, preventive, and personalized medicine: the Suita Study and meta-analysis of prospective cohort studies.

Background: Short and long sleep durations are common behaviors that could predict several cardiovascular diseases. However, the association between sleep duration and atrial fibrillation (AF) risk is not well-established. AF is preventable, and risk prevention approaches could reduce its occurrence. Investigating whether sleep duration could predict AF incidence for possible preventive interventions and determining the impact of various lifestyle and clinical characteristics on this association to personalize such interventions are essential. Herein, we investigated the association between sleep duration and AF risk using a prospective cohort study and a meta-analysis of epidemiological evidence. Methods: Data of 6898 people, aged 30-84 years, from the Suita Study, were analyzed. AF was diagnosed during the follow-up by ECG, medical records, checkups, and death certificates, while a baseline questionnaire was used to assess sleep duration. The Cox regression was used to compute the hazard ratios (HRs) and 95% confidence intervals (CIs) of AF risk for daily sleep ≤ 6 (short sleep), ≥ 8 (long sleep), and irregular sleep, including night-shift work compared with 7 h (moderate sleep). Then, we combined our results with those from other eligible prospective cohort studies in two meta-analyses for the short and long sleep. Results: In the Suita Study, within a median follow-up period of 14.5 years, short and irregular sleep, but not long sleep, were associated with the increased risk of AF in the age- and sex-adjusted models: HRs (95% CIs) = 1.36 (1.03, 1.80) and 1.62 (1.16, 2.26) and the multivariable-adjusted models: HRs (95% CIs) = 1.34 (1.01, 1.77) and 1.63 (1.16, 2.30), respectively. The significant associations between short and irregular sleep and AF risk remained consistent across different ages, sex, smoking, and drinking groups. However, they were attenuated among overweight and hypertensive participants. In the meta-analyses, short and long sleep durations were associated with AF risk: pooled HRs (95% CIs) = 1.21 (1.02, 1.42) and 1.18 (1.03, 1.35). No signs of significant heterogeneity across studies or publication bias were detected. Conclusion: Short, long, and irregular sleep could be associated with increased AF risk. In the context of predictive, preventive, and personalized medicine, sleep duration should be considered in future AF risk scores to stratify the general population for potential personalized lifestyle modification interventions. Sleep management services should be considered for AF risk prevention, and these services should be individualized according to clinical characteristics and lifestyle factors. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-022-00275-4.

Weight Change Since Age 20 and the Risk of Cardiovascular Disease Mortality: A Prospective Cohort Study.

AIM: Weight change could have many health outcomes. This study aimed to investigate the association between weight change and mortality risk due to total cardiovascular disease (CVD), ischemic heart disease (IHD), and stroke among Japanese. METHODS: We used Suita Study data from 4,746 people aged 30-79 years in this prospective cohort study. Weight change was defined as the difference between baseline weight and weight at age 20. We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of total CVD, IHD, and stroke mortality for 1) participants with a weight change (＞10, 5 to 10, -5 to -10, and ＜-10 kg) compared to those with stable weight (-4.9 to 4.9 kg) and 2) participants who moved from one body mass index category (underweight, normal weight, or overweight) to another compared to those with normal weight at age 20 and baseline. RESULTS: Within a median follow-up period of 19.9 years, the numbers of total CVD, IHD, and stroke mortality were 268, 132, and 79, respectively. Weight loss of ＞10 kg was associated with the increased risk of total CVD mortality 2.07 (1.29, 3.32) and stroke mortality 3.02 (1.40, 6.52). Moving from normal weight at age 20 to underweight at baseline was associated with the increased risk of total CVD, IHD, and stroke mortality: 1.76 (1.12, 2.77), 2.10 (1.13, 3.92), and 2.25 (1.05, 4.83), respectively. CONCLUSION: Weight loss, especially when moving from normal to underweight, was associated with the increased risk of CVD mortality.

Liver enzymes, alcohol consumption and the risk of diabetes: the Suita study.

AIM: We aimed to investigate the combined impact of liver enzymes and alcohol consumption on the diabetes risk. METHODS: Data on 5972 non-diabetic participants aged 30-79 years from the Suita study were analyzed. Diabetes incidence was surveyed every 2 years. Current daily alcohol consumption was defined as light drinking (< 23.0 g ethanol/day in men and < 11.5 g in women), moderate drinking (23.0-45.9 g and 11.5-22.9 g), and heavy drinking (≥ 46.0 g and ≥ 23.0 g). The nondrinkers category included both never-drinkers and former drinkers. RESULTS: During the median follow-up of 13 years, 597 incident diabetes cases were diagnosed. Higher levels of γ-glutamyltransferase (GGT), alanine aminotransferase (GPT), and aspartate aminotransferase (GOT) were associated with an increased diabetes risk, and current light drinkers had a lower risk of diabetes than nondrinkers. No sex differences were observed in these associations. Compared to nondrinkers having the lowest quartiles of liver enzymes, nondrinkers and current moderate/heavy drinkers having the highest quartiles had an increased risk of diabetes. However, no association was observed for current light drinkers having the highest quartiles of liver enzymes; the multivariable hazard ratios (95% CIs) in current light drinkers with the highest quartile of liver enzymes were 1.27 (0.68-2.37) for GGT, 1.05 (0.59-1.89) for GPT, and 0.76 (0.40-1.47) for GOT, respectively. CONCLUSION: High liver enzymes were associated with an increased diabetes risk. No increased diabetes risk was observed in current light drinkers, even in these who had high levels of liver enzymes.

Mild Hypertensive Retinopathy and Risk of Cardiovascular Disease: The Suita Study.

AIMS: This study aimed to investigate the association of mild hypertensive retinopathy with cardiovascular disease (CVD) risk. METHODS: A total of 7,027 residents aged 30-79 years without a history of CVD participated in the annual health checkups and retinal photography assessments. Retinal microvascular abnormalities were graded using the standard protocols and classified according to the Keith-Wagener-Barker classification. Mild hypertensive retinopathy was defined as grades 1 and 2. Cox proportional hazard model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for total CVD and its subtypes according to the presence and absence of mild hypertensive retinopathy. RESULTS: During a median follow-up of 17 years, 351 incident stroke and 247 coronary heart disease (CHD) cases were diagnosed. After adjustment for traditional cardiovascular risk factors, mild hypertensive retinopathy was positively associated with risk of CVD (multivariable HR=1.24; 95% CI, 1.04-1.49) and stroke (1.28; 1.01-1.62) but not with risk of CHD (1.19; 0.89-1.58). Generalized arteriolar narrowing and enhanced arteriolar wall reflex were positively associated with CVD risk, the multivariable HR (95% CI) was 1.24 (1.00-1.54) and 1.33 (1.02-1.74), respectively. Moreover, mild hypertensive retinopathy was positively associated with stroke risk in normotensive participants. CONCLUSION: Mild hypertensive retinopathy was positively associated with CVD and stroke risk in the urban Japanese population. Especially, generalized arteriolar narrowing and enhanced arteriolar wall reflex were positively associated with CVD risk. These findings suggested that retinal photography could be helpful for cardiovascular risk stratification in the primary cardiovascular prevention.

Serum uric acid levels and the risk of diabetes mellitus in premenopausal and postmenopausal women: the Suita study.

OBJECTIVE: The association between serum uric acid levels and the risk of diabetes mellitus in women stratified by menopausal status is not well-established. Therefore, we investigated this association among a cohort of Japanese urban women. METHODS: We conducted a prospective cohort study on 3,304 women (1,252 premenopausal and 2,052 postmenopausal), aged 30 to 79 years, with no prior cardiovascular disease or diabetes mellitus, and enrolled from a general urban population. Cox proportional hazard model was used to calculate hazard ratios and 95% confidence intervals (CIs) for incident diabetes mellitus according to serum uric acid quartiles. RESULTS: During 13.8 years of median follow-up, 219 incident diabetes mellitus cases were diagnosed. The incidence rate per 1,000 person-years was 3.42 in premenopausal women and 6.19 in postmenopausal women. After adjustment for potential risk factors, the multivariable hazard ratios (95% CIs) of the highest versus lowest serum uric acid quartiles were 1.56 (0.77-3.16) in premenopausal women, 2.00 (1.19-3.34) in postmenopausal women, and 1.81 (1.21-2.73) in all women. The interaction based on menopausal status was not significant ( P = 0.872). The corresponding population attributable fractions (95% CIs) were 13.3% (-8.9% to 31.1%), 19.1% (5.3%-30.9%), and 17.0% (5.6%-27.0%), respectively. CONCLUSIONS: Serum uric acid levels were positively associated with the risk of diabetes mellitus in postmenopausal women, but not in premenopausal women. However, the lack of an association in premenopausal women may have been due to limited power, so further research is required to confirm this menopausal status-specific association.

Prediction of the Health Effects of Food Peptides and Elucidation of the Mode-of-action Using Multi-task Graph Convolutional Neural Network.

Food proteins work not only as nutrients but also modulators for the physiological functions of the human body. The physiological functions of food proteins are basically regulated by peptides encrypted in food protein sequences (food peptides). In this study, we propose a novel deep learning-based method to predict the health effects of food peptides and elucidate the mode-of-action. In the algorithm, we estimate potential target proteins of food peptides using a multi-task graph convolutional neural network, and predict its health effects using information about therapeutic targets for diseases. We constructed predictive models based on 21,103 peptide-protein interactions involving 10,950 peptides and 2,533 proteins, and applied the models to food peptides (e. g., lactotripeptide, isoleucyltyrosine and sardine peptide) defined in food for specified health use. The models suggested potential effects such as blood-pressure lowering effects, blood glucose level lowering effects, and anti-cancer effects for several food peptides. The interactions of food peptides with target proteins were confirmed by docking simulations.