Self-Reported Sleep Duration and Bedtime Are Associated with Dementia Risk in Community-Dwelling People Aged 40-74 Years: The Murakami Cohort Study.

Background: Sleep is a potentially modifiable factor associated with dementia, including Alzheimer's disease, but current evidence supporting this is insufficient. Objective: This study aimed to determine whether sleep duration and bedtime patterns are associated with the risk of dementia among middle-aged and older people. Methods: This cohort study had an eight-year follow-up period. Participants were 13,601 community-dwelling people aged 40-74 years living in Murakami (Niigata, Japan). Data were collected using a self-administered questionnaire. Predictors were self-reported sleep duration and bedtime, and the outcome was newly-diagnosed dementia determined using the long-term care insurance database. Covariates were demographic characteristics, body mass index, smoking, alcohol consumption, total physical activity, insomnia symptoms, disease history, and either bedtime or sleep duration. Cox proportional hazard models were used to calculate hazard ratios (HRs). Results: The mean age of participants at baseline was 59.2 years. Over a mean follow-up period of 8.0 years, 319 cases of dementia were observed. A long self-reported sleep duration relative to the reference sleep duration (7 hours) was associated with increased dementia risk, with the "8 hours" group (adjusted HR = 1.30, 95% CI:0.99-1.73) and "≥9 hours" group (adjusted HR = 1.46, 95% CI:1.00-2.15) having an increased risk (marginally significant) relative to the reference group. Early bedtime was associated with increased dementia risk (adjusted p for trend = 0.0010), with the "21 : 00 or earlier" group (adjusted HR = 1.61, 95% CI:1.14-2.28) having an increased risk relative to the reference ("23 : 00"). Conclusions: A long self-reported sleep duration and early bedtime are both associated with increased dementia risk in middle-aged and older people.

Low plasma 25-hydroxyvitamin D levels are not associated with a high risk of recurrent falls in community-dwelling Japanese adults: the Murakami cohort study.

Reports on the association between vitamin D levels and fall risk have been mixed, and long-term follow-up studies are lacking. This 5-year cohort study of 5,343 community-dwelling Japanese people aged 40-74 years found that low vitamin D levels are not associated with a high risk of recurrent falls. PURPOSE: Findings of cohort studies on the association between plasma 25-hydoxyvitamin D (25[OH]D) levels and fall risk have been mixed, and long-term follow-up studies are lacking. The present study investigated whether low plasma 25(OH)D levels are longitudinally associated with a high risk of recurrent falls in adults. METHODS: This 5-year cohort study included 5,343 community-dwelling Japanese people aged 40-74 years. Baseline blood collection and a questionnaire survey were conducted in 2011-2013. Plasma 25(OH)D levels were determined and divided into quintiles after stratification by season, sex, and age group. Information on recurrent falls occurring in the year before the survey 5 years later was obtained, and participants with two or more falls were considered to have experienced recurrent falls. Covariates were sex, age, marital status, education, occupation, BMI, total physical activity levels, calcium intake, vitamin K intake, smoking, drinking, and disease history. RESULTS: Mean age and 25(OH)D levels were 60.9 years and 50.9 nmol/L, respectively. In the follow-up survey, 209 recurrent falls were reported. Plasma 25(OH)D levels were not significantly associated with the occurrence of recurrent falls in men, women, or men/women-combined (adjusted P for trend = 0.1198, 0.8383, and 0.2355, respectively). In men and men/women-combined, adjusted ORs for recurrent falls in the lowest quintile were significantly lower (adjusted OR = 0.42 and 0.59, respectively) than the middle quintile (reference). CONCLUSION: Low plasma 25(OH)D levels are not associated with a high risk of recurrent falls in middle-aged and older people. Further longitudinal studies will be needed to confirm our findings in other populations.

Complete sequence of carbapenem-resistant Ralstonia mannitolilytica clinical isolate co-producing novel class D ß-lactamase OXA-1176 and OXA-1177 in Japan.

In 2020, the Ralstonia mannitolilytica strain JARB-RN-0044 was isolated from a midstream urine sample of an elderly hospitalized patient in Japan and was highly resistant to carbapenem (i.e., imipenem, meropenem, and doripenem). Whole-genome sequencing revealed that the complete genome consists of two replicons, a 3.5-Mb chromosome and a 1.5-Mb large non-chromosomal replicon which has not been reported in R. mannitolilytica, and referred to as the "megaplasmid" in this study based on Cluster of Orthologous Group of proteins functional analysis. The strain JARB-RN-0044 harbored two novel OXA-60 and OXA-22 family class D ß-lactamase genes blaOXA-1176 and blaOXA-1177 on the megaplasmid. Cloning experiments indicated that Escherichia coli recombinant clone expressing blaOXA-1176 gene showed increased minimum inhibitory concentrations (MICs) of imipenem, meropenem, and doripenem, indicating that blaOXA-1176 gene encodes carbapenemase. In contrast, E. coli recombinant clone expressing blaOXA-1177 gene showed increased MICs of piperacillin and cefazolin, but not of carbapenem. Interestingly, the 44.6 kb putative prophage region containing genes encoding phage integrase, terminase, head and tail protein was identified in the downstream region of blaOXA-1176 gene, and comparative analysis with some previously reported R. mannitolilytica isolates revealed that the prophage region was unique to strain JARB-RN-0044. The existence of a highly carbapenem-resistant R. mannitolilytica isolate may raise human health concerns in Japan, where the population is rapidly aging.IMPORTANCERalstonia mannitolilytica is an aerobic non-fermenting Gram-negative rod commonly found in aquatic environments and soil. The bacteria can occasionally cause severe hospital-acquired bloodstream infections in immunocompromised patients and it has been recently recognized as an emerging opportunistic human pathogen. Furthermore, some R. mannitolilytica isolates are resistant to various antimicrobial agents, including ß-lactams and aminoglycosides, making antimicrobial therapy challenging and clinically problematic. However, clinical awareness of this pathogen is limited. To our knowledge, in Japan, there has been only one report of a carbapenem-resistant R. mannitolilytica clinical isolate from urine by Suzuki et al. in 2015. In this study, whole-genome sequencing analysis revealed the presence and genetic context of novel blaOXA-1176 and blaOXA-1177 genes on the 1.5 Mb megaplasmid from highly carbapenem-resistant R. mannitolilytica isolate and characterized the overall distribution of functional genes in the chromosome and megaplasmid. Our findings highlight the importance of further attention to R. mannitolilytica isolate in clinical settings.

Chronic Pain in the Lower Extremities and Low Back is Associated With Recurrent Falls in Community-Dwelling Japanese People Aged 40-74 Years.

OBJECTIVE: To determine the longitudinal association between chronic pain in the lower extremities and low back and the odds of recurrent falls in middle-aged and older people. DESIGN: A cohort study. SETTING: Communities in Japan. PARTICIPANTS: Participants were 7540 community-dwelling volunteers aged 40-74 years (N=7540). The baseline survey was a self-administered questionnaire conducted between 2011-2013. Predictors were presence of chronic pain in the knee, foot or ankle, and low back, with the degree of pain categorized as none, very mild/mild, moderate, or severe/very severe. Covariates in the multivariate model of chronic pain in a site were demographics, body mass index, physical activity level, disease history, and chronic pain in the other 2 sites. Logistic regression analysis was used to calculate odds ratios (ORs). INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Recurrent falls in the year before the 5-year follow-up survey. RESULTS: Mean participant age was 60.2 years. Higher degrees of chronic pain were associated with higher odds of recurrent falls for the knee (P=.0002) with a higher OR of 1.48 (95% CI: 1.11-1.97), for the foot or ankle (P=.0001) with a higher OR of 1.97 (95% CI: 1.36-2.86), and for the low back (P=.0470) with a higher OR of 1.45 (95% CI: 1.09-1.91) in those with any degree of pain relative to those without pain. Higher degrees of chronic knee pain were associated with higher odds of recurrent falls in women (P=.0005), but not in men (P=.0813). Meanwhile, higher degrees of chronic low back pain were associated with the odds of recurrent falls in men (P=.0065), but not in women (P=.8735). CONCLUSIONS: Chronic pain in the knee, foot or ankle, and lower back was independently and dose-dependently associated with a higher risk of recurrent falls. A marked sex-dependent difference was also noted in the association.

Body mass index, height, and osteoporotic fracture risk in community-dwelling Japanese people aged 40-74 years.

INTRODUCTION: The association between body size and fracture risk is complex and varies by sex and ethnicity. This study aimed to examine associations of body mass index (BMI) and height with osteoporotic fracture risk in middle-aged and older people. MATERIALS AND METHODS: This 10-year cohort study included 13,151 community-dwelling Japanese people aged 40-74 years. A self-administered questionnaire survey was conducted at baseline to obtain information on demographic characteristics, body size, lifestyle, and disease history. BMI (kg/m2) was categorized as underweight (< 18.5), low-normal (18.5-21.7), high-normal (21.8-24.9), overweight (25.0-29.9), and obese (≥ 30.0). Height was categorized into quartiles. All incident cases of major osteoporotic fractures, including fractures of the distal radius, neck of the humerus, neck or trochanter of the femur, and vertebrae, were obtained from medical records during follow-up. RESULTS: Mean participant age was 58.8 years. In men, the underweight group had a significantly higher hazard ratio (HR) for total fracture (adjusted HR = 2.46), and the obese group had significantly higher HRs for total (adjusted HR = 3.01) and vertebral (HR = 3.77) fractures relative to the reference (overweight) group. No significant associations were observed between BMI and risk of any fracture in women. Higher quartiles of height were associated with higher vertebral fracture risk (adjusted P for trend = 0.023) only in women. CONCLUSION: BMI and osteoporotic fracture risk showed a U-shaped association in men, whereas higher height was associated with higher vertebral fracture risk in women, suggesting sex-dependent differences in these associations.

Concordance between microsatellite instability testing and immunohistochemistry for mismatch repair proteins and efficient screening of mismatch repair deficient gastric cancer.

Microsatellite instability (MSI) testing, an established technique that has gained prominence in recent years for its predictive potential regarding the efficacy of immune checkpoint inhibitors, is used to evaluate DNA mismatch repair (MMR) deficiency (dMMR). As with other methods, the immunohistochemistry (IHC) of MMR proteins is also widely adopted. Although both techniques have been validated, their concordance rate remains unknown, particularly regarding non-colorectal cancer. Therefore, the aim of the present study was to explore and elucidate their concordance in the context of gastric cancer (GC). A total of 489 surgically resected primary GC tissues were analyzed to compare the results yielded by the MSI test and those from IHC. Of 488 GC cases, 56 (11.5%) exhibited a loss of MMR proteins, whereas 52 (10.7%) were classified as high-frequency MSI (MSI-H). The concordance rate between these two categories was 99.2%. The microsatellite markers BAT26 and MONO27 demonstrated 100% sensitivity and 99.5% specificity in detecting dMMR GC. In addition, histopathological analysis revealed that MSI-H was more prevalent in GCs exhibiting coexisting Tub2 and Por1 subtypes. However, four discordant cases were observed. All four cases were microsatellite-stable cases but exhibited loss of MLH1 protein expression with hypermethylation of the MLH1 promoter. The results of the present study highlight that while there is a strong concordance between MSI and IHC testing results for determining dMMR status, IHC testing may offer superior efficacy in detecting dMMR.

Sex Differences in the Association Between Body Mass Index and Dementia Risk in Community-Dwelling Japanese People Aged 40-74 Years.

BACKGROUND: The association between body mass index (BMI) and dementia risk is heterogeneous across age groups and might be influenced by sex. OBJECTIVE: This study aimed to clarify sex differences in the association between BMI and dementia risk in community-dwelling people. METHODS: This cohort study with an 8-year follow-up targeted 13,802 participants aged 40-74 years at baseline in 2011-2013. A self-administered questionnaire requested information on body size, including height, weight, and waist circumference (the values of which were validated by direct measurement), socio-demographics, lifestyle, and disease history. BMI was calculated and categorized as < 18.5 (underweight), 18.5-20.6 (low-normal), 20.7-22.6 (mid-normal), 22.7-24.9 (high-normal), 25.0-29.9 (overweight), and≥30.0 kg/m2 (obese). Incident cases of dementia were obtained from the long-term care insurance database. A Cox proportional hazards model was used to calculate multivariable-adjusted hazard ratios (HRs). RESULTS: The mean age of participants was 59.0 years. In men, higher BMI was associated with lower dementia risk (fully-adjusted p for trend = 0.0086). In women, the association between BMI and dementia risk was U-shaped; the "underweight," "low-normal," and "overweight" groups had a significantly higher risk (fully-adjusted HR = 2.12, 2.08, and 1.78, respectively) than the reference ("high-normal" group). These findings did not change after excluding dementia cases which occurred within the first four years of the follow-up period. CONCLUSION: Overweight/obese women, but not men, had an increased risk of dementia, suggesting that sex differences in adiposity might be involved in the development of dementia.

Alcohol consumption, smoking, and risk of dementia in community-dwelling Japanese people aged 40-74 years: The Murakami cohort study.

OBJECTIVE: Alcohol drinking and tobacco smoking have impacts on lifestyle-related diseases, but their association with dementia remains a debated topic. This study aimed to examine longitudinal associations between alcohol consumption, smoking, and dementia risk in middle-aged and older Japanese people. METHODS: This study used a cohort design with an 8-year follow-up. Participants were community-dwelling Japanese people (N = 13,802) aged 40-74 years. The baseline survey, including a self-administered questionnaire, was conducted in 2011-2013. Predictors were alcohol consumption and tobacco smoking. The outcome was incident dementia obtained from a long-term care insurance database. Covariates were demographics, lifestyle factors, body mass index, general health status, and history of stroke, diabetes, and depression. RESULTS: Participant mean age was 59.0 years. The 1-149, 150-299, and 300-449 g ethanol/week groups had significantly lower adjusted hazard ratios (HRs) (0.62, 0.59, and 0.47, respectively) compared with the reference group, with no significant linear association. HRs increased toward 1 when past-drinkers and those with poor health status and a disease history were excluded (0.80, 0.66, and 0.82, respectively). Higher smoking levels were dose-dependently associated with a higher HR (adjusted P for trend = 0.0105), with the ≥20 cigarettes/day group having a significantly higher adjusted HR (1.80). Heavy drinkers (≥449 g ethanol/week) with smoking habits, but not those without smoking habits, had higher dementia risk (P for interaction = 0.0046). CONCLUSION: Light-to-moderate alcohol consumption is associated with decreased dementia risk, and smoking is dose-dependently associated with increased dementia risk, with an interaction between high alcohol consumption and smoking on dementia risk.

Low plasma 25-hydroxyvitamin D levels are associated with an increased risk of depressive symptoms in community-dwelling Japanese people aged between 40 and 74 years: The Murakami cohort study.

BACKGROUND: Association between vitamin D levels and the occurrence of depression are not always consistent. The present cohort study aimed to determine this association in older adults, using a method for measuring vitamin D levels which is more accurate than those used in previous studies. METHODS: Participants were 3447 individuals aged 40-74 years without depressive symptoms at baseline who participated in the 5-year follow-up survey. The baseline investigation, including a self-administered questionnaire survey and blood collection, was conducted in 2011-2013. Plasma 25-hydroxyvitamin D (25[OH]D) levels were measured, and divided into overall quartiles summed up by sub-quartiles and stratified by age, sex, and season. The outcome was depressive symptoms determined by the CES-D (11-item, cut-off score of 6/7) 5 years later. Covariates were demographics, lifestyles, baseline CES-D score, and disease history. RESULTS: Mean plasma 25(OH)D levels were 58.0 nmol/L in men and 45.7 in women (P < 0.0001), and cumulative incidences of depressive symptoms were 249/1577 (15.8 %) in men and 313/1870 (16.7 %) in women (P = 0.4526). The lower 25(OH)D quartile group had higher adjusted ORs in men and women combined (P for trend = 0.0107) and women (P for trend = 0.0003), but not in men. Adjusted ORs of the lowest quartile group were significantly higher than the highest group in men and women combined (OR = 1.39, 95 % CI: 1.06-1.81) and women (OR = 1.89, 95 % CI: 1.31-2.72). LIMITATION: Depressive symptoms were self-reported. CONCLUSIONS: Low vitamin D levels were associated with a high risk of depressive symptoms, especially in women. Women are thus considered a major target for preventing vitamin D deficiency to address depression.

Physical activity and recurrent fall risk in community-dwelling Japanese people aged 40-74 years: the Murakami cohort study.

BACKGROUND: Falls are important causes of injury and mortality in older people, and associated medical costs can be enormous. Physical activity (PA) is a potential preventive factor for falls. However, few studies have examined the effect of different types of PA on fall prevention. This study aimed to evaluate the association between PA levels and the incidence of recurrent falls by type of PA in middle-aged and older people. METHODS: This cohort study targeted 7,561 community-dwelling individuals aged 40-74 years who did not experience recurrent falls in the year before baseline. Information on PA levels, demographics, body size, lifestyle, and fall/disease history was obtained using a self-administered questionnaire in the baseline survey. Levels of total PA, leisure-time PA, and non-leisure-time PA (occupation, commuting, and housework) were estimated using metabolic equivalent (MET) scores (MET-h/day; hours spent on a given activity per day multiplied by its MET intensity). PA levels were categorized into four groups. Falls were recorded as none, once, or twice or more (recurrent falls). The outcome of the study was the incidence of recurrent falls in the past year before a survey conducted 5 years after the baseline survey. Logistic regression analyses were performed to calculate odds ratios for recurrent falls. RESULTS: Higher total PA and non-leisure-time PA levels were associated with a higher risk of recurrent falls (P for trend = 0.0002 and 0.0001, respectively), with the highest total PA and non-leisure-time PA groups having a significantly higher adjusted OR (1.96 [95%CI:1.33-2.88] and 2.15 [95%CI:1.48-3.14], respectively) relative to the lowest group (reference). As for leisure-time PA, the medium group had a significantly lower adjusted OR (0.70 [95%CI:0.49-0.99]) relative to the reference group. By sex, the adjusted OR in the medium leisure-time PA group was significantly lower relative to the reference group in women (0.50 [95%CI: 0.29-0.85]) but not in men. CONCLUSIONS: Medium level leisure-time PA reduces the risk of recurrent falls in middle-aged and older people, whereas higher level non-leisure-time PA is associated with a higher risk of recurrent falls.

Leisure-Time and Non-Leisure-Time Physical Activities are Dose-Dependently Associated With a Reduced Risk of Dementia in Community-Dwelling People Aged 40-74 Years: The Murakami Cohort Study.

OBJECTIVE: Although physical activity (PA) in late life is considered a preventive factor for dementia, effects of different types of PAs on the development of dementia in early old age are unclear. This study aimed to determine the effect of leisure-time and non-leisure-time PAs on dementia risk in middle-aged and older adults during an 8-year follow-up. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: Participants were 13,773 community-dwelling individuals aged 40-74 years who completed the baseline self-administered questionnaire survey of the Murakami cohort study in 2011-2013. METHODS: Main predictors were leisure-time and non-leisure-time (commute, occupational work, and housework) PAs as assessed by MET score (MET-hour/d). The outcome was newly developed dementia determined using a long-term care insurance database. Covariates included demographics, lifestyle, body size, disease history, and PA level. Hazard ratios (HRs) were calculated using Cox proportional hazards models. RESULTS: Mean age of participants was 59.0 (SD 9.3) years. Higher levels of leisure-time PA were associated with lower HRs (adjusted P for trend <.001), with all tertiles having significantly lower HRs (low: 0.71, 95% CI 0.51-0.99; medium: 0.59, 95% CI 0.43-0.81; high: 0.55, 95% CI 0.41-0.75) relative to the reference (zero). Higher quartiles of non-leisure-time PA were associated with lower adjusted HRs for dementia (adjusted P for trend < .001), with the second-fourth quartiles having significantly lower HRs (second: 0.73, 95% CI 0.54-0.98; third: 0.59, 95% CI 0.43-0.81; fourth: 0.55, 95% CI 0.41-0.75) relative to the lowest quartile. These associations were robust regardless of sex and age group. CONCLUSIONS AND IMPLICATIONS: Both leisure-time and non-leisure-time PAs are independently and robustly associated with a reduced risk of dementia.

Serum 25-hydroxyvitamin D levels are not associated with impaired postural sway in community-dwelling older women: a 6-year follow-up study.

OBJECTIVES: A positive association between levels of blood 25-hydroxyvitamin D (25[OH]D), an index of vitamin D status, and physical balance has been reported from cross-sectional studies, but longitudinal studies are rare. The present study aimed to test the hypothesis that low serum 25(OH)D levels are longitudinally associated with impaired postural sway over a 6-year follow-up period in older women. METHODS: The present cohort consisted of 392 community-dwelling Japanese women aged ≥69 years. Baseline examinations included serum 25(OH)D and physical performance tests, including postural sway velocity. Standing postural sway was evaluated by measuring gravity-center sway velocity. Follow-up physical performance tests were conducted 6 years later. RESULTS: Mean subject age and serum 25(OH)D levels were 73.3 years (SD 3.7) and 61.0 nmol/L (SD 16.9), respectively. No significant association was found between 25(OH)D levels and changes in postural sway velocity (adjusted P for trend=0.72). Women with 25(OH)D <30 nmol/L tended to have lower Δpostural sway velocity than those with 25(OH)D ≥30 nmol/L (mean, -0.59 vs 0.37 cm/s, respectively; adjusted P=0.13). CONCLUSIONS: Vitamin D levels are not longitudinally associated with impaired postural sway in older women. Further longitudinal studies are needed to corroborate the results of this study.

Association of coffee, green tea, and caffeine with the risk of dementia in older Japanese people.

OBJECTIVES: Coffee, green tea, and caffeine are potential preventive factors for dementia, but the underlying evidence is insufficient. This study aimed to examine associations between the consumption of coffee, green tea, and caffeine and dementia risk in middle-aged and older people. METHODS: This was a cohort study with an 8.0-year follow-up. Participants were community-dwelling individuals (n = 13,757) aged 40-74 years. A self-administered questionnaire survey was conducted in 2011-2013. Predictors were the consumption of coffee/green tea, from which caffeine consumption was estimated. The outcome was incident dementia obtained from the long-term care insurance database. Covariates were demographic factors, body mass index, physical activity, energy, smoking, drinking, and disease history. Adjusted hazard ratios (HRs) were calculated using Cox proportional hazards models. HRs were also calculated using a Cox model with delayed entry. RESULTS: The number of dementia cases during the study period was 309. Participants with higher coffee consumption had lower HRs (adjusted p for trend = 0.0014), with the fifth quintile (≥326 ml/day) having a significantly lower HR (0.49, 95% confidence interval [CI]: 0.30-0.79) than the first quintile (<26 ml/day, reference). Similarly, participants with higher caffeine consumption had a significantly lower HR (adjusted p for trend = 0.0004) than the reference. The Cox model with delayed entry yielded similar results. These associations were significant in men, but not in women. Moreover, participants who consumed 2-2.9 cups/day and ≥3 cups/day of coffee had lower HRs (0.69, 95% CI: 0.48-0.98 and 0.53, 95% CI: 0.31-0.89, respectively) than those who consumed 0 cup/day. The association between green tea consumption and reduced dementia risk was significant (adjusted p for trend = 0.0146) only in the 60-69 years age subgroup. CONCLUSIONS: High levels of coffee and caffeine consumption were significantly associated with a reduced dementia risk in a dose-dependent manner, especially in men. Moreover, coffee consumption of ≥3 cups/day was associated with a 50% reduction in dementia risk.

Incidence of germline variants in Lynch syndrome-related genes among Japanese endometrial cancer patients aged 40 years or younger.

[Objective] Lynch syndrome (LS) is an autosomal dominant inherited disorder caused by a germline pathogenic variant in DNA mismatch repair (MMR) genes. Endometrial cancer frequently precedes another LS-associated tumor. This study aimed to clarify the incidence and features of LS in young Japanese endometrial cancer patients.[Methods] Sixty-five patients aged 40 years or younger, who were diagnosed with endometrial cancer, were enrolled in this study. Targeted sequencing of a hereditary colorectal cancer-related gene panel including the MMR genes MLH1, MSH2, MSH6, and PMS2 was conducted on DNA samples extracted from blood cells.[Results] Overall, 6 missense variants (2 in MSH2, 2 in MSH6, and 2 in PMS2), 1 inframe deletion variant in MSH2, 1 splice variant in MSH2, and 1 two-base substitution in the 3' untranslated region in MLH1 were detected in 9 (13.8%) patients. Among these, the splice variant c.1276G > T (p.Ile411_Gly426del16) in MSH2 was annotated as pathogenic, while other variants were of uncertain significance. The patient with the pathogenic variant had a family history of endometrial and colorectal cancer and was diagnosed with endometrial cancer at age 35.[Conclusion] The incidence of LS among Japanese endometrial cancer patients of reproductive age (≤ 40 years) in this study was at least 1.5%; however, 12.3% of patients had variants of uncertain significance in MMR genes.

Body mass index and risk of recurrent falls in community-dwelling Japanese aged 40-74 years: The Murakami cohort study.

AIMS: A prior meta-analysis found that obesity (body mass index [BMI] ≥ 30 kg/m2 ) was associated with a high fall risk, while being overweight (BMI≥25, <30 kg/m2 ) was associated with the lowest fall risk. However, whether these associations hold true for East Asians is unknown. This study aimed to assess the association between BMI and incidence of recurrent falls in Japanese aged 40-74 years. METHODS: This 5-year follow-up cohort study involved 7538 community-dwelling individuals who did not experience recurrent falls in the year before the baseline study. Information on demographics, body size, lifestyle, and disease history was obtained using a self-administered questionnaire. BMI was categorized as <18.5 (underweight), 18.5-20.6 (low-normal), 20.7-22.7 (mid-normal, reference), 22.8-24.9 (high-normal), and ≥ 25.0 kg/m2 (overweight). The outcome was recurrent falls reported, and fall history in the previous year was recorded as none, once, or twice or more (recurrent falls). RESULTS: Mean BMI was 23.5 kg/m2 (SD 2.9) for men and 22.7 kg/m2 (SD 3.2) for women. The adjusted odds ratio (OR) for recurrent falls in the BMI ≥25 group was significantly higher (1.41, 95%CI: 1.02-1.93) than that in the reference group. The adjusted OR in the BMI ≥25 group was significantly higher than that in the reference group for the age ≥ 60 subgroup (1.62, 95%CI: 1.09-2.40), but not for the age < 60 subgroup (OR = 1.04, 95%CI: 0.60-1.80). CONCLUSIONS: Being overweight may be a risk factor for recurrent falls in community-dwelling older Japanese. Further studies are needed to determine the underlying mechanism. Geriatr Gerontol Int 2021; 21: 498-505.

Quantitative evaluation of MSI testing using NGS detects the imperceptible microsatellite changed caused by MSH6 deficiency.

Microsatellite instability (MSI) is an effective biomarker for diagnosing Lynch syndrome (LS) and predicting the responsiveness of cancer therapy. MSI testing is conventionally performed by capillary electrophoresis, and MSI status is judged by visual assessment of allele size change. Here, we attempted to develop a quantitative evaluation model of MSI using next-generation sequencing (NGS). Microsatellite markers were analyzed in tumor and non-tumor tissues of colorectal cancer patients by NGS after a single multiplex polymerase chain reaction amplification. The read counts corresponding to microsatellite loci lengths were calculated independently of mapping against a reference genome, and their distribution was digitized by weighted mean. Weighted mean differences between tumor and non-tumor samples with different MSI status were assessed, and cut-off values for each marker in the discovery cohort were determined. Each microsatellite maker was defined as unstable if the weighted mean difference was greater than the cut-off value. In the discovery cohort, the evaluation model demonstrated sensitivity and specificity of 100% for all markers. In the validation cohort, MSI status determined by the new model was consistent with the outcome of the conventional method in 29/30 cases (97%). The single inconsistent case was classified as low-frequency MSI by the conventional method but considered MSI-high by NGS. Genetic testing for mismatch repair genes revealed a pathogenic variant in MSH6 in the discordant case. We successfully developed a quantitative evaluation method for determining MSI status using NGS. This is a robust and sensitive method and could improve LS diagnosis.

Dietary calcium and vitamin K are associated with osteoporotic fracture risk in middle-aged and elderly Japanese women, but not men: the Murakami Cohort Study.

Although dietary Ca, vitamin D and vitamin K are nutritional factors associated with osteoporosis, little is known about their effects on incident osteoporotic fractures in East Asian populations. This study aimed to determine whether intakes of these nutrients predict incident osteoporotic fractures. We adopted a cohort study design with a 5-year follow-up. Subjects were 12 794 community-dwelling individuals (6301 men and 6493 women) aged 40-74 years. Dietary intakes of Ca, vitamin D and vitamin K were assessed with a validated FFQ. Covariates were demographic and lifestyle factors. All incident cases of major osteoporotic limb fractures, including those of the distal forearm, neck of humerus, neck or trochanter of femur and lumbar or thoracic spine were collected. Hazard ratios (HR) for energy-adjusted Ca, vitamin D and vitamin K were calculated with the residual method. Mean age was 58·8 (sd 9·3) years. Lower energy-adjusted intakes of Ca and vitamin K in women were associated with higher adjusted HR of total fractures (Pfor trend = 0·005 and 0·08, respectively). When vertebral fracture was the outcome, Pfor trend values for Ca and vitamin K were 0·03 and 0·006, respectively, and HR of the lowest and highest (reference) intake groups were 2·03 (95 % CI 1·08, 3·82) and 2·26 (95 % CI 1·19, 4·26), respectively. In men, there were null associations between incident fractures and each of the three nutrient intakes. Lower intakes of dietary Ca and vitamin K were independent lifestyle-related risk factors for osteoporotic fracture in women but not men. These associations were robust for vertebral fractures, but not for limb fractures.

Predictors of decline in vitamin D status in middle-aged and elderly individuals: a 5-year follow-up study.

Little is known about predictors of decline in vitamin D status (vitamin D decline) over time. We aimed to determine demographic and lifestyle variables associated with vitamin D decline by sufficiently controlling for seasonal effects of vitamin D uptake in a middle-aged to elderly population. Using a longitudinal study design within the larger framework of the Murakami Cohort Study, we examined 1044 individuals aged between 40 and 74 years, who provided blood samples at baseline and at 5-year follow-up, the latter of which were taken on a date near the baseline examination (±14 d). Blood 25-hydroxyvitamin D (25(OH)D) concentrations were determined with the Liaison® 25OH Vitamin D Total Assay. A self-administered questionnaire collected demographic, body size and lifestyle information. Vitamin D decline was defined as the lowest tertile of 5-year changes in blood 25(OH)D (Δ25(OH)D) concentration (<6·7 nmol/l). Proportions of those with vitamin D decline were 182/438 (41·6 %) in men and 166/606 (27·4 %) in women (P < 0·0001). In men, risk of vitamin D decline was significantly lower in those with an outdoor occupation (P = 0·0099) and those with the highest quartile of metabolic equivalent score (OR 0·34; 95 % CI 0·14, 0·83), and higher in those with 'university or higher' levels of education (OR 2·92; 95 % CI 1·04, 8·19). In women, risk of vitamin D decline tended to be lower with higher levels of vitamin D intake (Pfor trend = 0·0651) and green tea consumption (Pfor trend = 0·0025). Predictors of vitamin D decline differ by sex, suggesting that a sex-dependent intervention may help to maintain long-term vitamin D levels.

Total physical activity and risk of chronic low back and knee pain in middle-aged and elderly Japanese people: The Murakami cohort study.

BACKGROUND: Specific components of physical activity, such as vigorous exercise and heavy occupational work, are known to increase the risk of chronic low back pain (CLBP) and chronic knee pain (CKP), but impacts of other components are less known. This study aimed to assess the relationship between total physical activity and risk of CLBP and CKP from a public health perspective. METHODS: Participants were 7,565 individuals, aged 40-74 years, who did not have CLBP or CKP, and who participated in the 5-year follow-up survey. A self-administered questionnaire was used to obtain information on demographics, body size and lifestyle (including physical activity) in the baseline survey in 2011-2013, and on CLBP and CKP using Short Form 36 (SF-36) in the follow-up survey. Sitting, standing, walking and strenuous work for occupational activity were assessed for total physical activity, and walking slowly, walking quickly, light to moderate exercise and strenuous exercise were assessed for leisure-time physical activity using metabolic equivalent hours/day (METs score). RESULTS: Mean age of participants was 60.1 years (SD, 8.8). Participants with higher METs scores had a significantly higher risk of CKP (p for trend = 0.0089, OR of 4th quartile = 1.29, 95% CI: 1.04-1.59 vs. 1st quartile), but not CLBP. An intermediate leisure-time METs score was associated with a lower risk of CLBP (OR = 0.75, 95%CI: 0.61-0.92 vs. 0 METs-group). CONCLUSIONS: A high level of total physical activity may increase the risk of CKP, whereas an intermediate level of leisure-time physical activity may decrease the risk of CLBP, in middle-aged and elderly individuals. SIGNIFICANCE: Evidence on the longitudinal association between total physical activity and CLBP and CKP in middle-aged and elderly people is lacking. We conducted a cohort study to assess this association, and found that high levels of total physical activity increased risk of CKP, and intermediate levels of leisure-time physical activity decreased risk of CLBP. This suggests that the effect of physical activity on chronic pain differed by pain site.