The Contributions of Knee Extension Strength and Hand Grip Strength to Factors Relevant to Physical Frailty: The Tanno-Sobetsu Study.

Sarcopenia is the core factor of frailty. This study specifically focused on lower limb muscle strength and examined muscle indices that indicate the risk of frailty or pre-frailty in older adults. The study included 327 community-dwelling individuals aged ≥65 years (43.7% male) who participated in the cohort. Frailty was defined based on five symptoms: weight loss, low activity level, exhaustion, weakness and slowness. Participants were classified into frail (three or more applicable), pre-frail (one to two applicable) and non-frail groups. Muscle strength (knee extension strength, toe grip strength and hand grip strength) were assessed, and appendicular muscle mass was assessed via a bioelectrical impedance analysis. The adjusted odds ratio (OR) of muscle indices for with frailty (frail group vs. pre-frail group) or pre-frailty (pre-frail group vs. non-frail group) were calculated. The prevalence of frail and pre-frail was 7% and 40%, respectively. Adjusted for age, sex, albumin and medical history, knee extension strength was significantly associated with frailty (odds ratio 0.95, 95% CI 0.92-0.98), while hand grip strength was associated with pre-frailty (odds ratio 0.92, 95% CI 0.88-0.97) but not with other muscle indices. This study is significant for identifying knee extension strength as a factor relevant to frailty in older adults considered pre-frailty, emphasizing the importance of this specific muscle measure in predicting and managing frailty.

Association of serum superoxide dismutase activity and the incidence of colorectal cancer in a nested case-control study.

BACKGROUND: Superoxide dismutase (SOD) is an antioxidant enzyme that degrades superoxide, a major causative factor in carcinogenesis. We assessed associations between serum SOD activities and incidence of colorectal carcinoma (CRC) in a case-control study nested in the Japan Collaborative Cohort (JACC) study. METHODS: At baseline, 39,242 subjects donated serum samples. Participants diagnosed with CRC during follow-up were regarded as cases. Odds ratios (ORs) for CRC incidence associated with SOD were evaluated with conditional logistic regression models. In the current study, 176 cases and 524 controls were analyzed. RESULTS: For the overall cohort, a decreasing trend in risk of CRC with increasing SOD was observed (P for trend=0.054) and the fourth quartile of SOD level showed the lowest risk compared to the first (OR=0.52, 95% confidence interval [CI]=0.29-0.93). This was significant in men (P for trend=0.001), with the fourth quartile of SOD level showing the lowest risk compared to the first (OR, 0.23; 95%CI, 0.09-0.60). It was also exclusively observed for rectal cancer and left-sided CRC (P for trend, 0.037 and 0.020, respectively), with the fourth quartile again showing the lowest risk compared to the first (OR, 0.28 and 0.38; 95%CI, 0.09-0.84 and 0.16-0.91, respectively). Limiting subjects to those followed-up over 2 years, all trends remained unchanged. CONCLUSIONS: Our findings suggest that serum SOD activity correlates inversely with risk of CRC, particularly in men and individuals with rectal cancer/left-sided CRC.

Preserved Lower Limb Muscle Mass Prevents Insulin Resistance Development in Nondiabetic Older Adults.

OBJECTIVE: To investigate roles of sarcopenia indexes in prediction of development of insulin resistance in nondiabetic older adults. DESIGN: A 2-year follow-up cohort. SETTING AND PARTICIPANTS: The Tanno-Sobetsu study, a prospective observational cohort, included 194 community-dwelling nondiabetic older adults during 2017-2019. METHODS: Lower limb, upper limb, appendicular, and trunk muscle masses by a bioelectrical impedance analysis, grip strength, knee extension torque, and walking speed were measured in study participants aged ≥65 years (79 men and 115 women) at baseline. Muscle mass and strength were divided by the weight, and then multiplied by 100 to calculate the weight ratio (%). Insulin resistance was assessed by homeostasis model (HOMA-IR) at baseline, and the study participants whose HOMA-IR was less than 1.73 at baseline were followed for a maximum of 2 years. The study endpoint was development of insulin resistance defined as HOMA-IR ≥1.73. The adjusted hazard ratio (HR) of each sarcopenia component for development of insulin resistance was calculated. RESULTS: Lower limb muscle mass (HR 0.88, 95% CI 0.79-0.98) and appendicular muscle mass (HR 0.89, 95% CI 0.81-0.99), but not other sarcopenia components, were associated with the development of insulin resistance, independently of sex and age, HOMA-IR, and waist circumference at baseline. CONCLUSIONS AND IMPLICATIONS: The loss of lower limb muscle mass is a significant risk factor for development of insulin resistance independently of obesity in nondiabetic older adults. The lower limb muscle mass may be a novel target of interventions for the prevention of diabetes in older adults.

Serum Soluble Fas Levels and Incidence of Liver Cancer in Nested Case-Control Study.

BACKGROUND: Soluble Fas (sFas) plays various roles in carcinogenesis and tumor dissemination by preventing apoptosis via binding to Fas ligand. We analyzed associations of serum sFas levels with the incidence of liver cancer in a prospective case-control study nested in the Japan Collaborative Cohort Study. METHODS: A baseline survey was conducted from 1988, with blood samples obtained from 39,242 subjects. Patients diagnosed with liver cancer were regarded as cases. Two or three controls were selected and matched for sex, age, and geographic area. Conditional logistic regression was used to estimate ORs for cancer incidence associated with sFas. RESULTS: This study contained 86 cases and 249 controls. After controlling for alcohol intake, body mass index, smoking, and hepatitis viral infection, participants with high sFas showed elevated risk of cancer (Ptrend = 0.003) and the third tertile of sFas showed a higher risk compared with the first tertile [OR, 3.53; 95% confidence interval (CI), 1.28-9.69]. In hepatocellular carcinoma, high sFas was associated with elevated risk (Ptrend < 0.001). In men and the elderly, subjects in the highest tertiles showed higher cancer risk. Limiting subjects to those followed for 3 years, high sFas was related to liver cancer risk (Ptrend = 0.033) and the third tertile showed a higher risk compared with the first (OR, 2.94; 95% CI, 0.94-9.14). CONCLUSIONS: High serum sFas may be related to future risk of liver cancer. IMPACT: Our findings highlight this biomarker for further analysis in pooled investigations with different/larger prospective cohorts.

Walking Speed Is Better Than Hand Grip Strength as an Indicator of Early Decline in Physical Function with Age in Japanese Women Over 65: A Longitudinal Analysis of the Tanno-Sobetsu Study Using Linear Mixed-Effects Models.

The decline in physical function with age is a major contributor to the need for long-term care. Age-related changes in hand grip strength, knee extension, and walking speed have been reported in cross-sectional studies, but longitudinal data are needed. This longitudinal study measured changes in these three measures among community-dwelling adults aged 65-89 years who participated in general health examinations between 2017 and 2019. Analyses were stratified by sex. Linear mixed-effects models adjusted for confounding factors were used to examine the interaction of different patterns of change with age of the three measures. A total of 284 participants were included in the analysis. The interaction term of age × walking speed, with age × handgrip strength as the reference, was statistically significant in women and showed different patterns in walking speed and hand grip strength. In men, none of the age × physical function interaction terms were significant in any model. For early recognition of the onset of physical function decline in older adults, any of the three measures may be used in men, but walking speed may be more suitable than hand grip strength in women. These findings may be useful in devising sex-specific screening strategies.

Association of Social Capital and Locus of Control with Perceived Health during the COVID-19 Pandemic in Japan.

Previous studies have indicated that social capital and locus of control influence mental health. Accordingly, we investigated the effect of social capital and locus of control on perceived physical and mental health in the general Japanese population during the COVID-19 pandemic. In order to conduct a cross-sectional study, in 2021, three thousand citizens were randomly selected from the Chitose City Resident Register according to ten strata of sex and age classes between 30 years and 79 years. Because thirteen persons moved away from the city, the survey was conducted for the remaining 2987 citizens. A total of 1430 citizens (712 males, 718 females) responded to the survey with their written informed consent (response rate, 47.9%). As a result, social capital measured three dimensions, namely social support, social participation, and trust and reciprocity, and internal locus of control was significantly inversely associated with it, but external locus of control was significantly positively associated with impaired physical and mental health in male and female subjects after adjustment of lifestyle habits and lifestyle change affected by the pandemic. Strengthening social capital and internal locus of control, and weakening external locus of control, may improve physical and mental health, even if the pandemic would bring about distress. Further longitudinal study is needed to examine the causal relationship among them.

Dairy products and the risk of developing prostate cancer: A large-scale cohort study (JACC Study) in Japan.

Dairy products have been indicated as a risk factor for prostate cancer. However, only a few epidemiological studies have reported dairy products as being a risk factor for prostate cancer in Japan, reporting contradictory results. We therefore investigated the association between the intake of dairy products and the occurrence of prostate cancer through a large-scale cohort study. The Japan Collaborative Cohort study analyzed approximately 110,000 residents from various Japanese districts who participated in our questionnaire survey during 1988-1990. The subjects of the present study were 26,464 men (age range: 40-79 years) from 24 districts wherein cancer incidence was reported. Their clinical course was followed up until 2009. Hazard ratios (HRs) were calculated using Cox's proportional hazards model, adjusted for age, survey area, family history of prostate cancer, body mass index, and total energy intake. For diet, we calculated the HRs associated with intermediate and high consumption of dairy products and compared them with those associated with low consumption. There were 412 cases of prostate cancer in the survey population. As dairy products, milk, yogurt, cheese, and butter were evaluated. Among them, milk consumption was associated with a significant risk (HR = 1.37, p = 0.009) and a dose-dependent response (p for trend = 0.009) adjusted for age and family history of prostate cancer, stratified by area. Milk and yogurt consumption showed a significantly positive risk and a dose-response relationship adjusted for age, family history of prostate cancer, body mass index, and total energy intake, stratified by area. In summary, a high intake of dairy products such as milk increased the risk of developing prostate cancer in Japanese men.

Insulin-Like Growth Factor 2 and Incidence of Liver Cancer in a Nested Case-Control Study.

BACKGROUND: Insulin-like growth factor (IGF)2 is a potent mitogen. To elucidate the relationship between IGF2 and risk of tumorigenesis, we analyzed associations between serum levels of IGF2 and incidence of liver cancer in a prospective case-control study nested in the Japan Collaborative Cohort study. METHODS: A baseline survey was conducted from 1988 using blood samples from 39,242 subjects. Those who had been diagnosed with liver cancer by 1997 were regarded as cases. For each case, we randomly selected two or three controls matched for sex, age, and residential area. Conditional logistic regression was used to estimate ORs for cancer incidence associated with IGF2. RESULTS: This analysis included 86 cases and 294 controls. Low IGF2 was associated with risk of future liver cancer (P trend <0.001). After controlling for alcohol intake, body mass index, smoking, hepatitis viral infection, IGF1, and IGF-binding protein-3, participants with low IGF2 displayed a higher risk of liver cancer (P trend < 0.001). Individuals in quintiles 2 to 5 showed lower risk compared with quintile 1 (OR range, 0.05-0.16). In both sexes and in both nonelderly and elderly groups, subjects in the lowest quintiles showed higher risks of liver cancer. Limiting subjects to those followed for 3 years, low IGF2 was associated with cancer risk (P trend < 0.001). CONCLUSIONS: Our findings suggest that low serum IGF2 level, especially below 460 ng/mL, is related to future risk of liver cancer. IMPACT: Our findings highlight this important biomarker for further analysis in large prospective cohorts and pooled investigation with other cohorts.

Comparing the extent of breast cancer tumors through contrast-enhanced ultrasound vs B-mode, opposed with pathology: evergreen study.

BACKGROUND: To prove the efficacy of contrast-enhanced ultrasound (CEUS) in determining the extent of resection, more evidence about B-mode and CEUS as opposed to pathology is required. We compared maximum tumor width measured on B-mode/CEUS images with that determined pathologically. METHODS: In this retrospective multicenter study, 152 operable breast cancer patients who had undergone both B-mode and CEUS were analyzed. Maximum tumor width on B-mode and CEUS, and on the postoperative pathological examination (P), was measured by the participating investigators. In addition, maximum width was assessed in B-mode and CEUS image sets by independent reviewers blinded to all patient information. We analyzed differences in maximum width between CEUS, B-mode and P. RESULTS: The mean widths as measured by the participating investigators were 15 ± 7 mm (B-mode), 19 ± 8 mm (CEUS), and 17 ± 9 mm (P). The difference subtracted P from B-mode was - 3 ± 7 mm (p < 0.0001), and that from CEUS was 1 ± 6 mm (p = 0.0163). The mean widths as measured by the independent reviewers were 16 ± 7 mm (B-mode) and 18 ± 7 mm (CEUS). The difference subtracted P from B-mode was - 2 ± 8 mm (p = 0.0114), while that from CEUS was 1 ± 7 mm (p = 0.1921). CONCLUSIONS: Maximum lesion width measurement showed a tendency to increase in the order of B-mode, to P and CEUS. The difference in measurement between P and B-mode was significant, but there was no significant between CEUS and P. These results provide additional information of tendency patterns in measuring the maximum lesion width through enhancement on CEUS.

Resveratrol improves motor function in patients with muscular dystrophies: an open-label, single-arm, phase IIa study.

Muscular dystrophies (MDs) are inherited disorders characterized by progressive muscle weakness. Previously, we have shown that resveratrol (3,5,4'-trihydroxy-trans-stilbene), an antioxidant and an activator of the protein deacetylase SIRT1, decreases muscular and cardiac oxidative damage and improves pathophysiological conditions in animal MD models. To determine whether resveratrol provides therapeutic benefits to patients with MDs, an open-label, single-arm, phase IIa trial of resveratrol was conducted in 11 patients with Duchenne, Becker or Fukuyama MD. The daily dose of resveratrol was 500 mg/day, which was increased every 8 weeks to 1000 and then 1500 mg/day. Primary outcomes were motor function, evaluated by a motor function measure (MFM) scale, muscular strength, monitored with quantitative muscle testing (QMT), and serum creatine kinase (CK) levels. Adverse effects and tolerability were evaluated as secondary outcomes. Despite the advanced medical conditions of the patients, the mean MFM scores increased significantly from 34.6 to 38.4 after 24 weeks of medication. A twofold increase was found in the mean QMT scores of scapula elevation and shoulder abduction. Mean CK levels decreased considerably by 34%. Diarrhoea and abdominal pain was noted in six and three patients, respectively. Resveratrol may provide some benefit to MD patients.

Epidemiological features of immunoglobulin G4-related sclerosing cholangitis in Japan.

BACKGROUND/PURPOSE: Epidemiological data on immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) are scarce. METHOD: We randomly selected healthcare facilities from a list of all facilities in Japan. The selection rate was determined according to a stratification based on the facility characteristics and scale. We sent questionnaires to the selected facilities enquiring about the number and sex of patients with IgG4-SC in 2018. Among responding facilities, we further inquired about the clinical characteristics of the patients with IgG4-SC. RESULTS: We selected 1180 departments from health centers across Japan. Of them, 532 (45.1%) responded to the questionnaires. The number of reported patients with IgG4-SC was 1045, and the estimated point prevalence was 2.18 (95% confidence interval, 2.13-2.23) per 100 000 population. In addition, we enrolled 1096 patients with IgG4-SC, combining data from previously and newly registered patients. Male patients comprised 79.5% of the population and patients aged 60-80 years had the highest risk for developing the disease. The follow-up period was 5.1 ± 4.0 years and the 5- and 10-year overall survival rates were 95.3% and 89.0%, respectively. CONCLUSIONS: The point prevalence of IgG4-SC was 2.18 per 100 000 population. The epidemiological features were similar to those observed in previous studies.

Intake of Common Alcoholic and Non-Alcoholic Beverages and Breast Cancer Risk among Japanese Women: Findings from the Japan Collaborative Cohort Study.

This study investigated the association between intake of common alcoholic and non-alcoholic beverages and breast cancer risk among Japanese women. This study included 33,396 Japanese women aged 40-79 years from 24 areas in Japan from the Collaborative Cohort study. During the follow-up period (≥20 years), 245 incidents or mortal breast cancers were documented. Multivariable logistic regression analysis was performed to assess the independent association between breast cancer risk and the intake of Japanese green tea, coffee, and alcohol. Japanese green tea was the most commonly consumed non-alcoholic beverage (81.6% of participants), followed by coffee (34.7%) and alcohol (23.6%). No significant associations were identified between the intake of green tea and coffee with breast cancer risk (odds ratio OR 1.15, 95% confidence interval [CI] 0.82-1.60, and OR 0.84, 95% CI 0.64-1.10, respectively). Alcohol intake was associated with significant breast cancer risk (OR 1.46, 95% CI 1.11-1.92), and even infrequent alcohol consumption (.

Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer.

Pancreatic cancer is the fourth leading cause of cancer-related deaths in Japan. To identify risk loci, we perform a meta-analysis of three genome-wide association studies comprising 2,039 pancreatic cancer patients and 32,592 controls in the Japanese population. Here, we identify 3 (13q12.2, 13q22.1, and 16p12.3) genome-wide significant loci (P < 5.0 × 10-8), of which 16p12.3 has not been reported in the Western population. The lead single nucleotide polymorphism (SNP) at 16p12.3 is rs78193826 (odds ratio = 1.46, 95% confidence interval = 1.29-1.66, P = 4.28 × 10-9), an Asian-specific, nonsynonymous glycoprotein 2 (GP2) gene variant. Associations between selected GP2 gene variants and pancreatic cancer are replicated in 10,822 additional cases and controls of East Asian origin. Functional analyses using cell lines provide supporting evidence of the effect of rs78193826 on KRAS activity. These findings suggest that GP2 gene variants are probably associated with pancreatic cancer susceptibility in populations of East Asian ancestry.

Insulin-like Growth Factor-1, Insulin-like Growth Factor Binding Protein-3 and the Incidence of Malignant Neoplasms in a Nested Case-Control Study.

Insulin-like growth factor (IGF)-1 is a potent mitogen, but IGF binding protein (IGFBP)-3 inhibits IGF1. To elucidate the relationship between both IGF1 and IGFBP and the risk of tumorigenesis, the association between IGF1 and IGFBP3 serum levels and of malignant tumor incidence was investigated in a prospective case-control study nested in the Japan Collaborative Cohort Study. A baseline survey was started in 1988-1990, 110,585 subjects were enrolled, and 35% of participants donated blood samples. Those who had been diagnosed with malignant tumors by 1997 were considered cases. The analysis involved 1,349 cases and 4,012 controls. Conditional logistic regression was used to estimate ORs for cancer incidence associated with IGF-related molecules. After controlling for alcohol intake, body mass index (BMI), and smoking, participants with high total-IGFBP3 and free-IGFBP3, which is estimated by the molar difference of (IGFBP3 - IGF1), had a risk of future neoplasms (P trend = 0.014 and 0.009, respectively), but those with IGF1 did not. People in the second to fifth quintiles had a lower risk than those in the first quintile (ORs 0.676-0.736 and 0.657-0.870, respectively). Limiting subjects to those followed for 3 years weakened the negative associations of total- and free-IGFBP3, whereas a positive relationship of free-IGF1, which was estimated by the molar ratio of IGF1/IGFBP3, was seen (P trend = 0.004, 0.002, and 0.013, respectively). After controlling for alcohol intake, smoking, BMI, and diabetes mellitus, the results were confirmed. These findings suggest that serum IGF1 and IGFBP3 are related to future risk of malignant neoplasms.

Individualized nutritional treatment for acute stroke patients with malnutrition risk improves functional independence measurement: A randomized controlled trial.

AIM: The aim of the present study was to investigate the effects of individualized nutritional treatment on the activities of daily living of acute stroke patients. METHODS: This was a randomized controlled study. The eligibility criteria were acute stroke, age >65 years and the presence of malnutrition risk. Between September 2016 and December 2017, 128 patients were assigned to either the standard or intensive group (individualized nutritional treatment). The intensive group received energy that was calculated using the Harris-Benedict equation. The main outcome measures were the total functional independence measurement gain from the time of assignment to the time of discharge from the recovery hospital or at 3 months after the stroke onset, and motor and cognitive functional independence measurement gains. RESULTS: Compared with the standard group, the intensive group had significantly higher median energy intake (P < 0.001); significantly greater functional independence measurement gains in the total score (42 vs. 22; P = 0.02) and motor subscore (P = 0.01), but similar cognitive subscore. CONCLUSION: Individualized nutritional treatment improved the activities of daily living of older acute stroke patients with malnutrition risk. Geriatr Gerontol Int 2019; ••: ••-••.

Lower limb muscle mass is associated with insulin resistance more than lower limb muscle strength in non-diabetic older adults.

AIM: We examined the association of muscle mass and muscle strength with insulin resistance, focusing on lower limb muscles. METHODS: This was a cross-sectional study, and participants were registered in 2017 from the Tanno-Sobetsu Study, a population-based cohort study. After excluding individuals aged <64 years or with a history of diabetes mellitus, 272 non-diabetic older adults (116 men, 156 women) met the inclusion criteria. According to the homeostasis model assessment of insulin resistance, the participants were divided into two groups; that is, the insulin resistance group (homeostasis model assessment of insulin resistance ≥1.73) and non-insulin resistance group (homeostasis model assessment of insulin resistance <1.73). Muscle mass (lower limb, upper limb, appendicular and trunk) and muscle strength (grip strength and knee extension torque) were measured and divided by the weight, and then multiplied by 100 to calculate the weight ratio (%). The adjusted odds ratio (OR) of each muscle index for risk of insulin resistance was calculated separately for both men and women. RESULTS: Lower limb muscle mass (OR 0.72, 95% CI 0.55-0.92 in men; OR 0.69, 95% CI 0.51-0.96 in women, respectively) and appendicular muscle mass (OR 0.75, 95% CI 0.61-0.94 in men; OR 0.72, 95% CI 0.54-0.95 in women, respectively), but not other muscle indexes, were associated with risk of insulin resistance, after adjusting for age, body mass index, highly sensitive C-reacting protein and smoking habits. CONCLUSIONS: Lower limb muscle mass of non-diabetic older adults is independently related to insulin resistance. Geriatr Gerontol Int 2019; 19: 1254-1259.

Cross-Cultural Validation Study of the Japanese Version of the ABILOCO-Kids in Ambulatory Children With Cerebral Palsy Using Rasch Analysis.

Aims: To determine the structural validity, construct validity, cross-cultural validity, internal consistency and test-retest reliability of the Japanese version of the ABILOCO-Kids in children with cerebral palsy. Methods: One-hundred sixteen parents of children with cerebral palsy (Gross Motor Function Classification System level I [n = 66], II [n = 32], and III [n = 18]) reported on walking ability using the Japanese version of the ABILOCO-Kids. For test-retest reliability, 23 participants were evaluated. Results: The mean ABILOCO-Kids logit score was 2.48 (range -7.44 to 5.83). Rasch analysis and principal component analysis were used to determine the structural validity. The construct validity was confirmed on the basis of differences in the ABILOCO-Kids scores among the Gross Motor Function Classification System levels. Cronbach's α and the item-to-total correlation coefficient supported the internal consistency. The intra-class correlation coefficient was 0.96, standard error of measurement 0.56 and minimal detectable change 1.55. The cross-cultural validity analyses showed differential item functioning according to the analyses of the invariance of item difficulty and person's ability estimates. Conclusions: The ABILOCO-Kids is a reliable and valid measure of walking ability in children with cerebral palsy in Japan. The lack of evidence on cross-cultural validity indicates we should interpret results cautiously in cases of international comparison.

Circulating insulin-like growth factor binding protein-3 and risk of gastrointestinal malignant tumors.

BACKGROUND AND AIM: Insulin-like growth factor-1 (IGF1) is a potent mitogen and is inhibited by IGF-binding protein-3 (IGFBP3). High serum IGF1 and low IGFBP3 are associated with increased risk of several carcinomas. Here, we assessed the relationship of these peptides with the risk of gastrointestinal malignancies, in a prospective case-control study nested in the Japan Collaborative Cohort Study. METHODS: The analysis involved 916 cases who had been diagnosed as gastrointestinal malignancies (C15-25) and 2306 controls. To estimate odds ratios for incidence of malignancies associated with these levels, a conditional logistic model was used. RESULTS: Both higher total and free IGFBP3 were associated with a decreased risk of tumor (P for trend < 0.001 and = 0.003, respectively). People in the second to fifth quintiles had lower risk compared to the first quintile (odds ratios ranged 0.532-0.650 and 0.582-0.725, respectively). After adjustment for IGF1, body mass index, drinking, and smoking, total IGFBP3 was inversely correlated with cancer risk (P for trend = 0.031). After adjustment, free IGFBP3 was inversely associated with the risk (P for trend = 0.007). Although total IGF1 was inversely correlated with tumor risk, it was not after controlling for IGFBP3 (P for trend = 0.007 and 0.589, respectively). Free IGF1 was not associated with the risk (P for trend = 0.361). Limiting subjects to those followed for over 3 years reinforced the inverted relationships of total and free IGFBP3 with risk for tumors (P for trend = 0.005 and 0.008, respectively). CONCLUSION: Both total and free IGFBP3 may be inversely associated with the incidence of gastrointestinal malignancies.

Increase trend in the prevalence and male-to-female ratio of primary biliary cholangitis, autoimmune hepatitis, and primary sclerosing cholangitis in Japan.

AIM: Autoimmune liver diseases (AILD) including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) impose a significant burden on public health, and it is important to estimate their prevalence. We carried out a nationwide, hospital-based, epidemiological survey of AIH, PBC, and PSC, and compared the results with those from previous surveys. METHOD: We randomly selected health-care facilities used in the survey from a list of all facilities in Japan. The selection rate was determined according to a stratification based on the facility characteristics and scale. We sent questionnaires to the selected facilities enquiring about the number and sex of patients with AILD who visited the facility in 2016. An identical survey was undertaken for AIH/PBC in 2004 and for PSC in 2007; we carried out a comparative analysis of these data. RESULTS: We selected 1793 departments from health centers all over Japan. Of them, 1078 (60.1%) responded to the questionnaires. The number of reported patients with AIH, PBC, and PSC was 8505, 10 847, and 906, respectively, and point prevalence was 23.9 (95% confidence interval, 23.3-24.5) for AIH (8.7 in 2004), 33.8 (33.0-34.6) for PBC (11.6 in 2004), and 1.80 (1.75-1.85) for PSC (0.95 in 2007) per 100 000 population. Male-to-female patient ratio of AILD was 1:4.3 for AIH (1:6.9 in 2004), 1:3.9 for PBC (1:7.1 in 2004), and 1:0.88 for PSC (1:1.4 in 2007). CONCLUSION: The current study indicates an increasing trend of prevalence as well as male-to-female patient ratio of AILD in Japan.

Differences in physical activity between seasons with and without snowfall among elderly individuals residing in areas that receive snowfall.

[Purpose] This study aimed to examine the influence of climatic conditions on the daily physical activities of elderly individuals by comparing the physical activity during seasons with and without snowfall. [Participants and Methods] In total, 35 participants attending the Health Promotion Program conducted by Chitose City Office participated in this study. The survey for the seasons with snowfall was conducted in February 2016, while the survey for the seasons without snowfall was conducted in September 2015. The physical activity of the participants was measured using a Kenz Lifecorder GS accelerometer. [Results] Physical activity was found to be significantly lower during seasons with snowfall than in seasons without snowfall. Multivariate analysis revealed that physical activity significantly increased with lower temperature during the seasons with snowfall, and it significantly increased with higher temperature and decreased with larger amounts of precipitation during the seasons without snowfall. [Conclusion] It was found that the climatic conditions affect the level of physical activity during seasons with and without snowfall. A lower level of physical activity was observed in areas that received snowfall than in areas that did not receive snowfall.