OBJECTIVES: To examine the effect of social support on the risk of caregiver's functional disability due to spouse's functional disability. DESIGN: Longitudinal study. SETTING AND PARTICIPANTS: In this cohort study using the Ohsaki Cohort 2006 Study data, the baseline survey was conducted from December 1, 2006, to December 15, 2006, and included 7598 older adults, including 3799 couples, ≥65 years of age. METHODS: The incidence of spouse's functional disability was defined as certification for the Long-term Care Insurance, which uses a nationally uniform standard of functional disability. The primary outcome was the incidence of the caregiver's functional disability, and the follow-up period was between December 16, 2006, and November 30, 2019. Five social support questionnaires were used to assess the degree of emotional and instrumental social support available to each participant. The Cox proportional hazards model was used to evaluate the incidence of functional disability among caregivers after the occurrence of spouses' functional disability. Subgroup analyses were also conducted according to the status of emotional and instrumental social support. RESULTS: The caregiver's functional disability increased significantly among those whose spouses had functional disability compared with those whose spouses had no disability (multivariate hazard ratio [HR], 1.86). Emotional and instrumental social support showed significant positive interactions on this association (emotional and instrumental support: P for interaction < .01 and < .01, respectively), and the risk of caregiver's disability was higher among those without social support than among those with social support (with emotional support: HR, 1.84; without emotional support: HR, 2.51; with instrumental support: HR, 1.85; without instrumental support: HR, 2.31). CONCLUSIONS AND IMPLICATIONS: Social support may help to alleviate the increased risk for caregiver's functional disability due to the spouse's functional disability.

BACKGROUND: Chronic kidney disease (CKD) contributes to decreased life expectancy. We examined the association between leisure-time physical activity (LTPA), non-leisure-time physical activity (non-LTPA) and kidney function. METHODS: This was a cross-sectional study including 32 162 community-dwelling adults aged ≥ 20 years from the Tohoku Medical MegaBank community-based cohort study. Kidney function was evaluated using cystatin C-based estimated glomerular filtration rate (eGFR) as well as self-reported LTPA and non-LTPA. CKD was defined as either eGFR decline (≤ 60 mL/min/1.73 m2) or presence of albuminuria (albumin-creatinine ≥ 30 mg/g). The association between domain-specific physical activity and kidney function, and CKD prevalence was examined using multivariable-adjusted ordinary least squares and modified Poisson models. RESULTS: The mean eGFR was 98.1 (± 13.2) mL/min/1.73 m2. 3 185 (9.9%) participants were classified as having CKD. The mean LTPA and non-LTPA levels were 2.9 (± 4.2) and 16.6 (± 14.2) METs-hour/day, respectively. For LTPA, in the adjusted model, the quartile groups with higher levels had a higher kidney function (β, 0.36; 95% confidence intervals [CI], [0.06, 0.66]; p = 0.019 for the 2nd quartile, β, 0.82; 95% CI, [0.51, 1.14]; p < 0.001 for the 3rd quartile, and β, 1.16; 95% CI, [0.83, 1.49]; p < 0.001 for the 4th quartile), whereas there were no apparent associations for prevalence of CKD. For non-LTPA, 4th quartile was associated with decreased eGFR (β, -0.42; 95% CI, [-0.72, -0.11]; p = 0.007) and higher prevalence of CKD prevalence (Prevalence ratio, 1.12; 95% CI, [1.02, 1.24]; p = 0.022). These associations with kidney function remained consistent in the subgroup analyses divided by demographic and biological variables. CONCLUSIONS: We observed a positive association between higher LTPA levels and better kidney function, but not association with CKD prevalence. In contrast, higher non-LTPA was negatively associated with both kidney function and CKD prevalence. These findings suggest that promoting LTPA is beneficial for kidney function.

Abstract Objective To investigate the inter-relationships among genetic risk, healthy lifestyle adherence, and hyperuricaemia susceptibility. Methods This prospective cohort study was conducted with 7,241 hyperuricaemia-free individuals aged ≥ 20 years from the Tohoku Medical Megabank Community-based cohort study. A comprehensive lifestyle score included body mass index, smoking, drinking, and physical activity, and a polygenic risk score (PRS) was constructed based on uric acid loci from a previous genome-wide association study meta-analysis. A multiple logistic regression model was used to estimate the association between genetic risk, healthy lifestyle, and hyperuricaemia incidence and calculate the area under the receiver operating characteristic curve (AUROC). Hyperuricaemia was defined as a uric acid level ≥7.0 mg/dl or a self-reported history of hyperuricaemia. Results Of the 7,241 adults (80.7% females; mean [SD] age: 57.7 [12.6] years), 217 (3.0%) developed hyperuricaemia during 3.5 years of follow-up. Genetic risk correlated with hyperuricaemia development (P for interaction = 0.287), and lifestyle risks were independently associated. Those with a high genetic risk and poor lifestyle had the highest risk (odds ratio: 5.34; 95% confidence interval [CI]: 2.61–12.10). Although not statistically significant, incorporating the PRS in the model with lifestyle information improved predictive ability (AUROC = 0.771, 95% CI: 0.736–0.806 for lifestyle; AUROC = 0.785, 95% CI: 0.751–0.819 for lifestyle and PRS; p = 0.07). Conclusion : A healthy lifestyle to prevent hyperuricaemia, irrespective of genetic risk, may mitigate the genetic risk. Genetic risk may complement lifestyle factors in identifying individuals at a heightened hyperuricaemia risk.

This study aimed to investigate the association of combination of birth weight and current body mass index (BMI) with the risk of hypertension in adulthood. This cross-sectional study used data from the Tohoku Medical Megabank Community-based Cohort Study conducted in Japan. A total of 10,688 subjects aged ≥20 years were eligible. We calculated the least square (LS) means of systolic blood pressure (SBP) and trend tests were performed to evaluate the linear relationships between birth weight categories and SBP. We also used a multivariate logistic regression analysis to assess the risk of hypertension associated with the combination of birth weight and current BMI. There was a statistically inverse association between birth weight and SBP in the 20-64 age group, but no significant association in the ≥65 age group. Low birth weight (LBW) with normal BMI group had a higher risk of hypertension than the normal or high birth weight groups with normal BMI. Furthermore, the group with LBW and BMI ≥25.0 kg/m2 was the highest risk for hypertension (adjusted odds ratio: 2.73; 95% CI, 2.04-3.65) compared to the reference group (birth weight 2500-3499 g and BMI 18.5-24.9 kg/m2). There was a significant association between LBW and subsequent risk of hypertension. In addition, participants with lower birth weights had a higher risk of hypertension than those with higher birth weights. However, even in participants with a lower birth weight, the risk of hypertension could be reduced when they maintained an optimal BMI.

BACKGROUND: Measurement of fractional exhaled nitric oxide (Feno) has been used in the diagnosis and management of asthma. Understanding the distribution of Feno in a larger resident population and its "healthy" subpopulation would contribute to the interpretation of Feno in clinical practice. OBJECTIVE: This study aimed to investigate the distribution and its associated factors in the adult population and its healthy subpopulations. METHODS: We conducted a cross-sectional study of 8,638 men and 17,288 women aged 20 years or older living in Miyagi prefecture, Japan. We investigated the distribution of Feno and its associated factors in all subjects, a subpopulation with no history of upper and lower airway diseases (healthy subpopulation 1), and a subpopulation with no history of upper and lower airway diseases, normal lung function, and no positivity for other biomarkers of type 2 inflammation (healthy subpopulation 2). RESULTS: The distribution of Feno in healthy subpopulations, especially in healthy subpopulation 2 (median [interquartile range], 17 [12-23] with 95th percentile of 36 ppb) was lower than in all subjects (19 [13-26] ppb with 95th percentile of 47 ppb). In healthy subpopulation 1, 10.3% had elevated Feno (≥35 ppb), and elevated Feno was positively associated with factors including obstructive ventilatory defect, blood eosinophilia, house dust mite-specific IgE positivity, and history of hypertension. Male sex was associated with elevated Feno in all subjects and healthy subpopulations. CONCLUSION: The distribution of Feno in the healthy subpopulation supports the validity of the criteria (≥35 ppb) currently used in Japan for the diagnosis of asthma.

Depression is comorbid with somatic diseases; however, the relationship between depressive symptoms and hypertension (HT), a risk factor for cardiovascular events, remains unclear. Home blood pressure (BP) is more reproducible and accurately predictive of cardiovascular diseases than office BP. Therefore, we focused on home BP and investigated whether depressive symptoms contributed to the future onset of home HT. This prospective cohort study used data from the Tohoku Medical Megabank Community-Cohort Study (conducted in the Miyagi Prefecture, Japan) and included participants with home normotension (systolic blood pressure (SBP) < 135 mmHg and diastolic blood pressure (DBP) < 85 mmHg). Depressive symptoms were evaluated using the Center for Epidemiologic Studies Depression Scale-Japanese version at the baseline survey. In the secondary survey, approximately 4 years later, the onset of home HT was evaluated (SBP ≥ 135 mmHg or DBP ≥ 85 mmHg) and was compared in participants with and without depressive symptoms. Of the 3 082 (mean age: 54.2 years; females: 80.9%) participants, 729 (23.7%) had depressive symptoms at the baseline survey. During the 3.5-year follow-up, 124 (17.0%) and 388 (16.5%) participants with and without depressive symptoms, respectively, developed home HT. Multivariable adjusted odds ratios were 1.37 (95% confidence interval (CI): 1.02-1.84), 1.18 (95% CI: 0.86-1.61), and 1.66 (95% CI: 1.17-2.36) for home, morning, and evening HT, respectively. This relationship was consistent in the subgroup analyses according to age, sex, BP pattern, and drinking habit. Depressive symptoms increased the risk of new-onset home HT, particularly evening HT, among individuals with home normotension. This prospective cohort study revealed that depressive symptoms are risk factors for new-onset home hypertension, particularly evening hypertension among individuals with home normotension. Assessing home blood pressure in individuals with depressive symptoms is important for the prevention of hypertension and concomitant cardiovascular diseases.

BackgroundDementia is the leading cause of disability and imposes a significant burden on society. Previous studies have suggested an association between metabolites and cognitive decline. Although the metabolite composition differs between Western and Asian populations, studies targeting Asian populations remain scarce.MethodsThis cross-sectional study used data from a cohort survey of community-dwelling older adults aged ≥ 60 years living in Miyagi, Japan, conducted by Tohoku Medical Megabank Organization between 2013 and 2016. Forty-three metabolite variables quantified using nuclear magnetic resonance spectroscopy were used as explanatory variables. Dependent variable was the presence of cognitive decline (≤ 23 points), assessed by the Mini-Mental State Examination. Principal component (PC) analysis was performed to reduce the dimensionality of metabolite variables, followed by logistic regression analysis to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for cognitive decline.ResultsA total of 2,940 participants were included (men: 49.0%, mean age: 67.6 years). Among them, 1.9% showed cognitive decline. The first 12 PC components (PC1-PC12) accounted for 71.7% of the total variance. Multivariate analysis showed that PC1, which mainly represented essential amino acids, was associated with lower odds of cognitive decline (OR = 0.89; 95% CI, 0.80-0.98). PC2, which mainly included ketone bodies, was associated with cognitive decline (OR = 1.29; 95% CI, 1.11-1.51). PC3, which included amino acids, was associated with lower odds of cognitive decline (OR = 0.81; 95% CI, 0.66-0.99).ConclusionAmino acids are protectively associated with cognitive decline, whereas ketone metabolites are associated with higher odds of cognitive decline.

No study, to our knowledge, has constructed a polygenic risk score based on clinical blood pressure and investigated the association of genetic and lifestyle risks with home hypertension. We examined the associations of combined genetic and lifestyle risks with hypertension and home hypertension. In a cross-sectional study of 7027 Japanese individuals aged ≥20 years, we developed a lifestyle score based on body mass index, alcohol consumption, physical activity, and sodium-to-potassium ratio, categorized into ideal, intermediate, and poor lifestyles. A polygenic risk score was constructed with the target data (n = 1405) using publicly available genome-wide association study summary statistics from BioBank Japan. Using the test data (n = 5622), we evaluated polygenic risk score performance and examined the associations of combined genetic and lifestyle risks with hypertension and home hypertension. Hypertension and home hypertension were defined as blood pressure measured at a community-support center ≥140/90 mmHg or at home ≥135/85 mmHg, respectively, or self-reported treatment for hypertension. In the test data, 2294 and 2322 participants had hypertension and home hypertension, respectively. Both polygenic risk and lifestyle scores were independently associated with hypertension and home hypertension. Compared with those of participants with low genetic risk and an ideal lifestyle, the odds ratios for hypertension and home hypertension in the low genetic risk and poor lifestyle group were 1.94 (95% confidence interval, 1.34-2.80) and 2.15 (1.60-2.90), respectively. In summary, lifestyle is important to prevent hypertension; nevertheless, participants with high genetic risk should carefully monitor their blood pressure despite a healthy lifestyle.

AIM: This study examined the relationship between genetic risk, healthy lifestyle, and risk of developing diabetes. METHODS: This prospective cohort study included 11,014 diabetes-free individuals ≥ 20 years old from the Tohoku Medical Megabank Community-based cohort study. Lifestyle scores, including the body mass index, smoking, physical activity, and gamma-glutamyl transferase (marker of alcohol consumption), were assigned, and participants were categorized into ideal, intermediate, and poor lifestyles. A polygenic risk score (PRS) was constructed based on the type 2 diabetes loci from the BioBank Japan study. A multiple logistic regression model was used to estimate the association between genetic risk, healthy lifestyle, and diabetes incidence and to calculate the area under the receiver operating characteristic curve (AUROC). RESULT: Of the 11,014 adults included (67.8% women; mean age [standard deviation], 59.1 [11.3] years old), 297 (2.7%) developed diabetes during a mean 4.3 (0.8) years of follow-up. Genetic and lifestyle score is independently associated with the development of diabetes. Compared with the low genetic risk and ideal lifestyle groups, the odds ratio was 3.31 for the low genetic risk and poor lifestyle group. When the PRS was integrated into a model including the lifestyle and family history, the AUROC significantly improved to 0.719 (95% confidence interval [95% CI]: 0.692-0.747) compared to a model including only the lifestyle and family history (0.703 [95% CI, 0.674-0.732]). CONCLUSION: Our findings indicate that adherence to a healthy lifestyle is important for preventing diabetes, regardless of genetic risk. In addition, genetic risk might provide information beyond lifestyle and family history to stratify individuals at high risk of developing diabetes.

AIM: To evaluate the association between housing and psychological damage caused by the Great East Japan Earthquake (GEJE) and modifiable risk factors (MRFs) of dementia for general population of older adults. METHODS: This cross-sectional study enrolled 29 039 community-dwelling older adults (mean age 69.1 ± 2.9 years, 55.5% women). We evaluated disaster-related damage (by complete or not complete housing damage) and psychological damage (by post-traumatic stress reaction [PTSR]) after the GEJE using a self-report questionnaire. MRFs encompassed the presence of depression, social isolation, physical inactivity, smoking, and diabetes. We examined the association between disaster-related damage and MRFs using ordinary least squares and modified Poisson regression models adjusted for sociodemographic and health status variables. RESULTS: Complete housing damage and PTSR were identified in 2704 (10.0%) and 855 (3.2%) individuals, respectively. The number of MRFs was significantly larger for the individuals with complete housing damage (β = 0.23; 95% confidence interval [CI]: 0.19-0.27) and PTSR (β = 0.60; 95% CI: 0.53-0.67). Prevalence ratios (PRs) for depression and physical inactivity were higher in individuals with complete housing damage. The PRs for all domains of the MRFs were significantly higher in individuals with PTSR. CONCLUSIONS: Housing and psychological damage caused by the GEJE were associated with an increased risk factor of dementia. To attenuate the risk of dementia, especially among older victims who have experienced housing and psychological damage after a disaster, multidimensional support across various aspects of MRFs is required. Geriatr Gerontol Int 2024; ••: ••-••.

BACKGROUND/AIMS: The objective of this research is to examine factors related to irritable bowel syndrome (IBS) prevalence in a large population-based study. METHODS: A cross-sectional study was conducted with participants in the Miyagi part of the Tohoku Medical Megabank Project Community-Based cohort study who completed the Rome II Modular Questionnaire. Multivariate odds ratios (ORs) for the presence of IBS and 95% confidence intervals (95% CIs) for the reference group were calculated for each factor. Additionally, a stratified analysis was performed by sex and age group (20-49 years, 50-64 years, and ≥ 65 years). RESULTS: Among 16 252 participants, 3025 (18.6%) had IBS, comprising 750 men (15.5%) and 2275 women (19.9%). Multivariate ORs for the presence of IBS decreased significantly with each year of age (OR, 0.98; 95% CI, 0.98-0.99). Moreover, compared with the reference group, ORs for the presence of IBS were significantly higher in individuals whose home was partially damaged by the Great East Japan Earthquake, those with < 16 years of education, those who spent less time walking, those with high perceived stress (1.77, 1.57-2.01), those with high psychological distress (1.58, 1.36-1.82), and those with high symptoms of depression (1.76, 1.60-1.94). In stratified analyses, a significant relationship was found between psychological factors and IBS prevalence in all sex and age groups. CONCLUSIONS: This large cross-sectional population-based cohort study identified several factors associated with IBS prevalence. Psychological factors were significantly associated with IBS prevalence across all age groups and sexes.

BACKGROUND: Upper and lower extremity muscle strength can be used to predict health outcomes. However, the difference between the relation of upper extremity muscle and of lower extremity muscle with physiological factors is unclear. This study aimed to evaluate the association between physiological data and muscle strength, measured using grip and leg extension strength, among Japanese adults. METHODS: We conducted a cross-sectional study of 2,861 men and 6,717 women aged ≥ 20 years living in Miyagi Prefecture, Japan. Grip strength was measured using a dynamometer. Leg extension strength was measured using a hydraulic isokinetic leg press machine. Anthropometry and physiological data, including blood pressure, calcaneal ultrasound bone status, pulmonary function, carotid echography, and blood information, were assessed. We used a general linear model adjusted for age, body composition, and smoking status to evaluate the association between muscle strength and physiological factors. RESULTS: Grip and leg extension strength were positively associated with bone area ratio, vital capacity, forced vital capacity, forced expiratory volume in one second, and estimated glomerular filtration rate, and negatively associated with waist circumference and percentage body fat mass in both the sexes. Diastolic blood pressure was positively associated with grip strength in both the sexes and leg extension strength in men, but not women. High-density lipoprotein cholesterol and red blood cell counts were positively associated with grip and leg extension strength in women, but not men. In both the sexes, pulse rate, total cholesterol, and uric acid were consistently associated with only leg extension strength, but not grip strength. In women, glycated hemoglobin demonstrated negative and positive associations with grip and leg extension strength, respectively. CONCLUSIONS: Grip and leg extension strength demonstrated similar associations with anthropometry, pulmonary function, and estimated glomerular filtration rate, but the associations with the other factors were not always consistent.

BACKGROUND: The relationship between blood cell profiles, including hemoglobin (Hb) levels and inflammatory hematological ratios, and mental health problems currently remains unclear. AIM: This study aimed to investigate the relationship between blood cell profiles and mental health issues, including depressive state and sleep disturbance, while adjusting for potential demographic confounders. METHODOLOGY: This retrospective, cross-sectional, observational study used a population-based medical database from the Tohoku Medical Megabank Project with more than 60,000 volunteers. Data on age, sex, daily tobacco use, body mass index, and self-reported scores on the Kessler Psychological Distress Scale (K6), Athens Insomnia Scale (AIS), and the Center for Epidemiologic Studies Depression Scale (CES-D) were collected. RESULTS: A total of 62,796 volunteers (23,663 males and 39,133 females), aged ≥20 years at the time of the blood test, agreed to participate in this study. Among the evaluated blood cell profiles, Hb, hematocrit, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were significantly correlated with the K6, AIS, and CES-D scores, with strong statistical significance (p<0.0001 for all) in bivariate correlation analyses. A significant adjusted odds ratio (aOR) of the Hb level for elevated CES-D scores (aOR=0.965 [95% CI: 0.949-0.981], p<0.0001) was confirmed after adjusting for demographic data and daily tobacco use using a logistic regression model. Sensitivity analyses revealed that these associations existed in both males and females but were more prominent in the former. In male participants, a low Hb level was significantly associated with an elevated AIS score. The evaluated inflammatory hematological ratios, including NLR, PLR, and monocyte-to-lymphocyte ratio (MLR), also showed significant aORs with the K6, AIS, and CES-D scores after adjusting for demographic background. CONCLUSION: Low Hb levels and elevated inflammatory hematological ratios (NLR, MLR, and PLR) were associated with depressive state and sleep disturbances in the general population.

Abstract Risk factors for hypertension have been emphasized in the Japanese Society of Hypertension Guidelines for the Management of Hypertension. However, large-scale studies on the association of smoking, potassium excretion, and gamma-glutamyl transferase level with BP in the Japanese population are limited. We conducted a cross-sectional study to examine the association between hypertension risk factors and systolic blood pressure in the Tohoku Medical Megabank Community-based Cohort Study (23,446 men and 38,921 women aged ≥20 years). A model adjusted for age, body mass index, smoking status, drinking status, estimated daily salt intake, potassium excretion, (or urinary sodium-to-potassium ratio), gamma-glutamyl transferase, physical activity, education level, status of damage to homes during the Great East Japan Earthquake, and residential areas was used. The average age and systolic blood pressure were 62.5 (10.3) years for men and 59.6 (11.3) years for women, 128.9 (16.7) mmHg for men and 124.7 (17.5) mmHg for women, respectively. Body mass index estimated daily salt intake, urinary sodium-to-potassium ratio and gamma-glutamyl transferase levels were positively associated with systolic blood pressure. Compared with never-drinkers, current drinkers who consumed 23–45 g/day and ≥46.0 g/day had significantly increased systolic blood pressure. Conversely, current smokers (1-10 cigarettes/day and 11-20 cigarettes/day) were inversely associated with systolic blood pressure compared to never-smokers. Overall, systolic blood pressure was associated with gamma-glutamyl transferase and hypertension risk factors, including body mass index, alcohol consumption, estimated daily salt intake, urinary sodium-to-potassium ratio, and potassium excretion. Our findings support the notion that lifestyle modifications should be attempted to prevent hypertension.

BACKGROUND: The purpose of this study was to report the basic profile of the Miyagi Prefecture part of a repeated center-based survey during the second period (2nd period survey) of the Tohoku Medical Megabank Community-Based Cohort Study (TMM CommCohort Study), as well as the participants' characteristics based on their participation type in the baseline survey. METHODS: The 2nd period survey, conducted from June 2017 to March 2021, included participants of the TMM CommCohort Study (May 2013 to March 2016). In addition to the questionnaire, blood, urine, and physiological function tests were performed during the 2nd period survey. There were three main ways of participation in the baseline survey: Type 1, Type 1 additional, or Type 2 survey. The 2nd period survey was conducted in the same manner as the Type 2 survey, which was based on the community support center (CSC). RESULTS: In Miyagi Prefecture, 29,383 (57.7%) of 50,967 participants participated in the 2nd period survey. The participation rate among individuals who had visited the CSC was approximately 80%. Although some factors differed depending on the participation type in the baseline survey, the 2nd period survey respondents in the Type 1 and Type 2 survey groups at baseline had similar traits. CONCLUSIONS: The 2nd period survey of the TMM CommCohort Study provided detailed follow-up information. Following up on the health conditions of the participants will clarify the long-term effects of disasters and contribute to personalized prevention.

AIMS: Although fat mass (FM) and fat-free mass (FFM) have an impact on lipid metabolism, the relationship between different body composition phenotypes and lipid profiles is still unclear. By dividing the FM and FFM by the square of the height, respectively, the f at mass index (FMI) and fat-free mass index (FFMI) can be used to determine the variations in body composition. This study aimed to investigate the relationship of combined FMI and FFMI with low-density lipoprotein cholesterol (LDL-C) levels. METHODS: This cross-sectional study comprised 5,116 men and 13,630 women without cardiovascular disease and without treatment for hypertension, and diabetes. Following sex-specific quartile classification, FMI and FFMI were combined into 16 groups. Elevated LDL-C levels were defined as LDL-C ≥ 140 mg/dL and/or dyslipidemia treatment. Multivariable logistic regression models were used to examine the relationships between combined FMI and FFMI and elevated LDL-C levels. RESULTS: Overall, elevated LDL-C levels were found in 1,538 (30.1%) men and 5,434 (39.9%) women. In all FFMI subgroups, a higher FMI was associated with elevated LDL-C levels. Conversely, FFMI was inversely associated with elevated LDL-C levels in most FMI subgroups. Furthermore, the groups with the highest FMI and lowest FFMI had higher odds ratios for elevated LDL-C levels than those with the lowest FMI and highest FFMI. CONCLUSIONS: Regardless of FFMI, FMI was positively associated with elevated LDL-C levels. Conversely, in the majority of FMI subgroups, FFMI was inversely associated with elevated LDL-C levels.

Masked hypertension is a risk factor for cardiovascular diseases. However, masked hypertension is sometimes overlooked owing to the requirement for home blood pressure measurements for diagnosing. Mental status influences blood pressure. To reduce undiagnosed masked hypertension, this study assessed the association between depressive symptoms and masked hypertension. This cross-sectional study used data from the Tohoku Medical Megabank Project Community-Based Cohort Study (conducted in Miyagi Prefecture, Japan, from 2013) and included participants with normotension measured at the research center (systolic blood pressure<140 mmHg and diastolic blood pressure <90 mmHg). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (Japanese version). Masked hypertension was defined as normotension measured at the research center and home hypertension (home systolic blood pressure ≥135 mmHg or home diastolic blood pressure ≥85 mmHg). The study comprised 6705 participants (mean age: 55.7 ± 13.7 years). Of these participants, 1106 (22.1%) without depressive symptoms and 393 (23.2%) with depressive symptoms were categorized to have masked hypertension. Sex-specific and age-adjusted least mean squares for home blood pressure, not for research blood pressure were significantly higher in the group with depressive symptoms in both sex categories. The multivariate odds ratio for masked hypertension in the patients with depressive symptoms was 1.72 (95% confidence interval: 1.26-2.34) in male participants and 1.30 (95% confidence interval: 1.06-1.59) in female ones. Depressive symptoms were associated with masked hypertension in individuals with normotension measured at the research center. Depressive symptoms may be one of the risk factors for masked hypertension. Depressive symptoms were associated with masked hypertension in individuals with normotension measured at research center.

Abstract This study aimed to examine whether risk of withdrawal from HTTx was higher in coastal areas that were severely damaged by tsunami than in inland areas. We conducted a cross-sectional study of 9218 participants aged ≥20 years in Miyagi, Japan. The odds ratios (ORs) and confidence interval (CI) for withdrawal from HTTx in coastal and inland groups were compared using multivariate logistic regression analysis, adjusting for potential confounders. In total, 194 of 5860 and 146 of 3358 participants in the inland and coastal groups, respectively, withdrew from HTTx treatment. OR (95%CI) of withdrawal from HTTx in the coastal group was 1.46 (1.14–1.86) compared to the inland group. According to housing damage, ORs (95% CI) in the no damage, partially destroyed, and more than half destroyed coastal groups compared with the no damage inland group were 1.62 (1.04–2.50), 1.69 (1.17–2.45), and 1.08 (0.71–1.65), respectively. In conclusion, the risk of HTTx withdrawal for participants whose homes in coastal areas were relatively less damaged was significantly higher compared with those in inland areas, while the risk of HTTx withdrawal for participants whose homes were more than half destroyed was not. Post-disaster administrative support for disaster victims is considered vital for continuation of their treatment.

AIM: The influence of family history of diabetes, probably reflecting genetic and lifestyle factors, on the association of combined genetic and lifestyle risks with diabetes is unknown. We examined these associations. METHODS: This cross-sectional study included 9,681 participants in the Tohoku Medical Megabank Community-based Cohort Study. A lifestyle score, which was categorized into ideal, intermediate, and poor lifestyles, was given. Family history was obtained through a self-reported questionnaire. A polygenic risk score (PRS) was constructed in the target data (n=1,936) using publicly available genome-wide association study summary statistics from BioBank Japan. For test data (n=7,745), we evaluated PRS performance and examined the associations of combined family history and genetic and lifestyle risks with diabetes. Diabetes was defined as non-fasting blood glucose ≥ 200 mmHg, HbA1c ≥ 6.5%, and/or self-reported diabetes treatment. RESULTS: In test data, 467 (6.0%) participants had diabetes. Compared with a low genetic risk and an ideal lifestyle without a family history, the odds ratio (OR) was 3.73 (95% confidence interval [CI], 1.92-7.00) for a lower genetic risk and a poor lifestyle without a family history. Family history was significantly associated with diabetes (OR, 3.58 [95% CI, 1.73-6.98]), even in those with a low genetic risk and an ideal lifestyle. Even among participants who had an ideal lifestyle without a family history, a high genetic risk was associated with diabetes (OR, 2.49 [95% CI, 1.65-3.85]). Adding PRS to family history and conventional lifestyle risk factors improved the prediction ability for diabetes. CONCLUSIONS: Our findings support the notion that a healthy lifestyle is important to prevent diabetes regardless of genetic risk.

BACKGROUND: Olfactory function decline has recently been reported to be associated with a risk of cognitive impairment. Few population-based studies have included younger adults when examining the association between olfactory test data with multiple odor intensities and suspected cognitive impairment. OBJECTIVE: We investigated the association between high-resolution olfactory test data with fewer odors and suspected cognitive impairments. We also examined the differences between older and younger adults in this association. METHODS: The Japanese version of the Montreal Cognitive Assessment (MoCA-J) was administered to 1,450 participants, with three odor-intensity-level olfactometry using six different odors. Logistic regressions to discriminate suspected cognitive impairment were conducted to examine the association, adjusted for age, sex, education duration, and smoking history. Data were collected from the Program by Tohoku University Tohoku Medical Megabank Organization, with an additional olfactory test conducted between 2019 and 2021. RESULTS: We generally observed that the lower the limit of distinguishable odor intensity was, the higher the MoCA-J score was. The combination of spearmint and stuffy socks contributed most to the distinction between suspected and unsuspected cognitive impairment. Furthermore, the association was significant in women aged 60-74 years (adjusted odds ratio 0.881, 95% confidence interval [0.790, 0.983], p = 0.024). CONCLUSIONS: The results indicate an association between the limit of distinguishable odor intensity and cognitive function. The olfactory test with multiple odor intensity levels using fewer odors may be applicable for the early detection of mild cognitive impairment, especially in older women aged 60-74 years.

AIM: People with high normal blood pressure (BP) have a higher risk of cardiovascular events than those with normal BP; therefore, progression to hypertension (HT) should be prevented. We aimed to assess the HT risk using central BP and carotid intima media thickness (CIMT) in people with high normal BP. METHODS: This prospective cohort study used the Tohoku Medical Megabank Community-Based Project Cohort Study (conducted from 2013 in Miyagi Prefecture in Japan). The participants had a high normal BP, defined as a systolic BP of 120-139 mmHg and diastolic BP ＜90 mmHg using brachial BP measurement during the baseline survey. The outcome was new-onset HT during the secondary survey, conducted four years after the baseline survey. RESULTS: Overall, 4,021 participants with high normal BP during the baseline survey, with an average age of 58.7 years, were included; 1,030 (26%) were diagnosed with new-onset HT during the secondary survey, 3.5± 0.7 years after the baseline survey. The multivariable odds ratio (95% confidence interval) for HT in the highest versus lowest quartile of central BP was 1.7 (1.2-2.4, p=0.0030), and that of CIMT was 1.8 (1.4-2.4, p＜0.001). Subgroup analysis according to age (＜60 and ≥ 60 years) and sex revealed that the central BP was influential in groups with younger age and female individuals; CIMT was influential in all groups. CONCLUSIONS: Higher central BP and thicker CIMT at the baseline were correlated with new-onset HT in individuals with high normal BP, independent of brachial systolic BP and other cardiovascular risk factors.

BACKGROUND: The aims were to use Japanese data from the Rome Foundation Global Epidemiological Study (RFGES) to test the hypotheses that severity of gastrointestinal (GI) symptoms and psychosocial disturbance are ordered as Rome IV irritable bowel syndrome (IBS) > Rome III IBS > DGBI, not IBS > others. METHODS: Subjects were 2504 Japanese in the RFGES. We assessed DGBI/IBS diagnoses with Rome IV/III, IBS Symptom Severity Scale (IBS-SSS), Patient Health Questionnaire (PHQ) for anxiety/depression and non-GI somatic symptoms, PROMIS-10 for quality of life (QOL), Work Productivity and Activity Impairment (WPAI) Questionnaire, parts of Self-reported IBS Questionnaire (SIBSQ) for meal effect and stress effect, Food Frequency Questionnaire, and medication questions. KEY RESULTS: The prevalence of Rome IV DGBI was as follows; IBS-C 0.5%, IBS-D 0.8%, IBS-M 0.8%, IBS-U 0.1%, unspecified functional bowel disorder 10.7%, postprandial distress syndrome 2.2%, and epigastric pain syndrome 0.3%. Rome III IBS prevalence; IBS-C 3.0%, IBS-D 3.1%, IBS-M 2.7%, and IBS-U 0.6%. Comparison among Rome IV IBS (n = 54), Rome III IBS (n = 197), other DGBI (n = 746), others (n = 1389) revealed significant order as Rome IV IBS > Rome III IBS > other DGBI > others in IBS-SSS, anxiety/depression, activity impairment, non-GI symptoms, physical QOL, mental QOL, exacerbated symptoms by meals and perceived stress (all p < 0.001). CONCLUSIONS & INFERENCES: These findings support the study hypotheses. Data from Japan as a culturally homogenous country suggest Rome IV IBS is more severe and hence has more gut-brain psychobehavioral involvement than Rome III IBS.

White blood cell (WBC) count profiles in anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) and anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are still unknown. This study evaluated the total WBC count, differential WBC counts, monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-lymphocyte ratio (NLR) in patients with these diseases within three months from an attack before acute treatment or relapse prevention and compared the profiles with those in matched volunteers or in multiple sclerosis (MS) patients. AQP4-NMOSD patients (n = 13) had a higher neutrophil count (p = 0.0247), monocyte count (p = 0.0359), MLR (p = 0.0004), and NLR (p = 0.0037) and lower eosinophil (p = 0.0111) and basophil (p = 0.0283) counts than those of AQP4-NMOSD-matched volunteers (n = 65). Moreover, patients with MOGAD (n = 26) had a higher overall WBC count (p = 0.0001), neutrophil count (p < 0.0001), monocyte count (p = 0.0191), MLR (p = 0.0320), and NLR (p = 0.0002) than those of MOGAD-matched volunteers (n = 130). The three demyelinating diseases showed similar levels of the total and differential WBC counts; however, MOGAD and MS showed different structures in the hierarchical clustering and distributions on a two-dimensional canonical plot using differential WBC counts from the other three groups. WBC count profiles were similar in patients with MOGAD and MS but differed from profiles in matched volunteers or patients with AQP4-NMOSD.

BACKGROUND: Although fat mass index (FMI) and fat-free mass index (FFMI) affect lung function, FMI and FFMI are not independent of each other since FMI and FFMI were calculated as fat mass and fat-free mass divided by height squared, respectively. We aimed to examine the association of combined FMI and FFMI with lung function. METHODS: In this cross-sectional study, lung function was evaluated using forced expiratory volume at 1 s and forced vital capacity was measured using spirometry. Both FMI and FFMI were classified into sex-specific quartiles (16 groups). Analysis of covariance was used to assess the associations of combined FMI and FFMI with lung function. The trend test was conducted by stratifying the FMI and FFMI, scoring the categories from 1-4 (lowest-highest), and entering the number as a continuous term in the regression model. RESULTS: This study included 3,736 men and 8,821 women aged ≥20 years living in Miyagi Prefecture, Japan. The mean FEV1 (standard deviation) was 3.0 (0.7) L for men and 2.3 (0.5) L for women. The mean FVC was 3.8 (0.7) L for men and 2.8 (0.5) L for women. The FMI was inversely associated with lung function among all FFMI subgroups in both sexes. Conversely, FFMI was positively associated with lung function in all FMI subgroups in both sexes. CONCLUSIONS: Higher FMI was associated with lower lung function independent of FFMI; higher FFMI was associated with higher lung function independent of FMI. Reducing FMI and maintaining FFMI might be important for respiratory health.

BACKGROUND: Neonatal maternal separation (MS) has been used to model long-lasting changes in behavior caused by neuroplastic changes associated with exposure to early-life stress. Earlier studies showed that transient gut inflammation can influence the development of irritable bowel syndrome (IBS). A prevailing paradigm of the etiology of IBS is that transient noxious events lead to long-lasting sensitization of the neural pain circuit, despite complete resolution of the initiating event. This study characterizes the changes in behaviors and neuroendocrine parameters after MS and early-phase trinitrobenzene sulfonic acid (TNBS)-induced colitis. We tested the hypothesis that MS and gut inflammation synergistically induce (1) hyperactivity in male rats and anxiety-like behaviors in female rats and (2) activation of the HPA axis in female rats and deactivation of the HPA axis in male rats after colorectal distention (CRD). METHODS: Male and female rat pups were separated from their dams for 180 min daily from postnatal day (PND) 2 to PND 14 (MS). Early-phase colitis was induced by colorectal administration with TNBS on PND 8. The elevated plus-maze test was performed at 7 weeks. Tonic CRD was performed at 60 mmHg for 15 min at 8 weeks. Plasma ACTH and serum corticosterone were measured at baseline or after the CRD. Analysis of variance was performed for comparison among controls, TNBS, MS, and MS + TNBS. RESULTS: In male rats, the time spent in open arms significantly differed among the groups (p < 0.005). The time spent in open arms in male MS + TNBS rats was significantly higher than that of controls (p < 0.009) or TNBS rats (p < 0.031, post hoc test). Female rats showed no difference in the time spent in open arms among the groups. MS and gut inflammation induced an increase in plasma ACTH in female rats but not in male rats at baseline. CONCLUSIONS: These findings suggest that MS and gut inflammation synergistically induce hyperactive behavior or exaggerated hypothalamic-pituitary-adrenal axis function depending on sex.

AIM: We examined the association between the carotid intima medica thickness (cIMT) and risk factors for atherosclerosis based on the Japan Atherosclerosis Society 2022 Atherosclerosis Prevention Guideline. METHODS: Using data from the Tohoku Medical Megabank Community-based Cohort Study, we performed a cross-sectional study that enrolled 13,366 participants (age ≥ 20 years) with an analysis of covariance to assess associations between cIMT and risk factors for atherosclerosis. The maximum common carotid artery was measured using high-resolution B-mode ultrasound. Analysis was conducted in the model adjusted for age, sex, smoking status, drinking status, body mass index (BMI), systolic blood pressure (SBP), glycated hemoglobin (HbA1c), high-density lipoprotein-cholesterol (HDL-C), non-high-density lipoprotein-cholesterol (non-HDL-C), and height. RESULTS: In this study cohort, the average age and cIMT were 57.3 (13.8) years and 0.61 (0.13) mm, respectively, which included 3,988 males (29.8%). Males had a higher cIMT than did the females. Age, height, BMI, SBP, HbA1c, and non-HDL-C were positively associated with cIMT. HDL-C was inversely associated with cIMT. Compared with never drinkers, current drinkers (≥ 46.0 g/day) had a significantly decreased cIMT. CONCLUSIONS: The cIMT was associated with atherosclerosis risk factors including age, sex, BMI, SBP, HbA1c, non-HDL-C, and HDL-C, and adequate control of risks in high-risk individuals might be required to prevent atherosclerotic cardiovascular diseases.

BACKGROUND: Although several studies have shown an inverse association between lung function and hypertension, few studies have examined the association between lung function and hypertension among never-smokers, and no study has investigated the association between lung function and home hypertension. We investigated the associations between lung function and hypertension in a Japanese population. INDIVIDUALS AND METHODS: We conducted a cross-sectional study of 3728 men and 8795 women aged 20 years or older living in Miyagi Prefecture, Japan. Lung function was assessed using forced expiratory volume at 1 s (FEV1) and forced vital capacity (FVC), measured by spirometry. Hypertension was defined as a casual blood pressure at least 140/90 mmHg and/or self-reported treatment for hypertension. Home hypertension was defined as morning home blood pressure at least 135/85 mmHg and/or self-reported treatment for hypertension. Multivariate logistic regression models adjusted for potential confounders were used to assess the association between lung function and hypertension. RESULTS: The mean ages (±SD) of men and women were 60.1 (±14.0) years and 56.2 (±13.4) years, respectively, and 1994 (53.5%) men and 2992 (34.0%) women had hypertension. In the multivariable models, FEV1 and FVC were inversely associated with hypertension. Inverse associations between lung function and hypertension were observed even among never-smokers. Furthermore, reduced lung function was associated with higher prevalence of home hypertension in men and women. CONCLUSION: Reduced lung function was associated with higher prevalence of hypertension, independent of smoking status. Assessment of the lung function or blood pressure may be required in individuals with reduced lung function or hypertension.

INTRODUCTION: Consumption of green kiwifruit is known to relieve constipation. Previous studies have also reported improvements in gastrointestinal (GI) comfort. We investigated the effect of consuming green kiwifruit on GI function and comfort. METHODS: Participants included healthy controls (HC, n = 63), patients with functional constipation (FC, n = 60) and constipation-predominant irritable bowel syndrome (IBS-C, n = 61) randomly assigned to consume two green kiwifruit or psyllium (7.5 g) per day for 4 weeks, followed by a 4-week wash-out, then the other treatment for 4 weeks. The primary outcome was the number of complete spontaneous bowel movements (CSBM) per week. Secondary outcomes of GI comfort, including the gastrointestinal symptom rating scale (GSRS), a validated instrument. Data (intent-to-treat (ITT)) were analysed as difference from baseline using repeated measures analysis of variance suitable for AB/BA cross-over design. RESULTS: Consumption of green kiwifruit was associated with a clinically relevant increase of ≥ 1.5 CSBM per week (FC; 1.53, p<0.0001, IBS-C; 1.73, p=0.0003), and significantly improved measures of GI comfort (GSRS total score) in constipated participants (FC, p<0.0001; IBS-C, p<0.0001). No significant adverse events were observed. DISCUSSION: This study provides original evidence that the consumption of a fresh, whole fruit has demonstrated clinically relevant increases in CSBM and improved measures of GI comfort constipated populations. Green kiwifruit are a suitable dietary treatment for relief of constipation and associated GI comfort.

AIM: Impaired lung function is associated with atherosclerotic vascular events. Carotid intima-media thickness (cIMT) is a marker for subclinical atherosclerosis. However, few studies have examined the association between lung function and cIMT among never smokers or individuals stratified by age. We investigated the association between lung function and cIMT in the Japanese population. METHODS: We conducted a cross-sectional study of 3,716 men and 8,765 women aged 20 years or older living in Miyagi Prefecture, Japan. Lung function was evaluated using forced expiratory volume at 1 s (FEV1) and forced vital capacity (FVC) was measured using spirometry. The maximum common carotid artery was measured using high-resolution B-mode ultrasound. An analysis of covariance was used to assess associations between lung function and cIMT and adjusted for potential confounders. A linear trend test was conducted by scoring the categories from 1 (lowest) to 4 (highest) and entering the score as a continuous term in the regression model. RESULTS: After adjusting for potential confounders including passive smoking, lower FEV1 and FVC were associated with higher cIMT in both men and women (P＜0.001 for linear trend). This association was confirmed even when we restricted our study to never smokers. Furthermore, even when we stratified by age, an inverse association between lung function and cIMT was confirmed in middle-aged (40-64 years) and elderly participants (65-74 years). CONCLUSIONS: Lower lung function was associated with higher cIMT in the Japanese population independent of age and smoking. Assessment of atherosclerosis or lung function may be required for individuals with lower lung function or atherosclerosis.

BACKGROUND: Previous observational studies have shown similarities in cardiometabolic risk factors between spouses. It is still possible that this result reflects the age similarity of spouses rather than environmental factors of spouses (e.g. cohabitation effect). To clarify the importance of mate cardiometabolic risk factors for similarity of environmental factors, it is necessary to examine whether they are observed in random male-female pairs while maintaining the age of the spousal pairs. This study aimed to determine whether the similarities found between spousal pairs for cardiometabolic risks were also observed between random male-female pairs. METHODS: This cross-sectional study included 5,391 spouse pairs from Japan; data were obtained from a large biobank study. For pairings, women of the same age were randomly shuffled to create new male-female pairs of the same age as that of the original spouse pairs. Similarities in cardiometabolic risk factors between the random male-female pairs were analysed using Pearson's correlation or age-adjusted logistic regression analyses. RESULTS: The mean ages of the men and women were 63.2 and 60.4 years, respectively. Almost all cardiometabolic risk factors similarities were not noted in cardiometabolic risk factors, including the continuous risk factors (anthropometric traits, blood pressure, glycated haemoglobin level, and lipid traits); lifestyle habits (smoking, drinking, and physical activity); or diseases (hypertension, type 2 diabetes mellitus, and metabolic syndrome) between the random male-female pairs. The age-adjusted correlation coefficients ranged from - 0.007 for body mass index to 0.071 for total cholesterol. The age-adjusted odds ratio (95% confidence interval) for current drinkers was 0.94 (0.81 - 1.09); hypertension, 1.07 (0.93 - 1.23); and type 2 diabetes mellitus, 1.08 (0.77 - 1.50). CONCLUSION: In this study, few similarities in cardiometabolic risk factors were noted among the random male-female pairs. As spouse pairs may share environmental factors, intervention strategies targeting lifestyle habits and preventing lifestyle-related diseases may be effective.

AIM: Although many epidemiological studies have shown that obesity assessed by body mass index is associated with carotid intima-media thickness (cIMT), few studies have evaluated fat-free mass, which is a component of body composition. We investigated the associations between the combined fat mass index (FMI) and fat-free mass index (FFMI) with cIMT. METHODS: We conducted a cross-sectional study of 3,873 men and 9,112 women aged 20 years or older who lived in Miyagi prefecture, Japan. The FMI and FFMI were calculated as fat mass and fat-free mass divided by height squared, respectively. The indices were classified into sex-specific quartiles and were combined into 16 groups. The maximum common carotid artery was measured using high-resolution B-mode ultrasound. An analysis of covariance was used to assess associations between the combined FMI and FFMI with cIMT adjusted for age and smoking status. The linear trend test was conducted by stratifying the FMI and FFMI, scoring the categories from 1 (lowest) to 4 (highest), and entering the number as a continuous term in the regression model. RESULTS: In multivariable models, a higher FMI was not related to higher cIMT in men and women in most FFMI subgroups. Conversely, a higher FFMI was related to higher cIMT in all FMI subgroups (p＜0.001 for linear trend). CONCLUSIONS: FMI was not associated with cIMT in most FFMI subgroups. Conversely, FFMI was positively associated with cIMT independently of FMI.

AIM: Caregiver burden is known to negatively affect a partner's health. Given the important role of physical and mental stress in mortality, a higher caregiver burden might be associated with an increased incidence of fatal events. However, previous studies of the effects of the partner's caregiving on mortality have shown inconsistent results. Thus, the purpose of the present longitudinal study was to determine if there is an association between a spouse's functional disability and mortality in the older Japanese population. METHODS: A baseline survey was carried out with 7598 participants in 2006. Information on the date of functional disability, death or emigration was retrieved from the Ohsaki City government. Functional disability was defined as receiving a certification for long-term care insurance in Japan. After a follow-up period of a maximum of 87 months, 1316 of the participants died and Cox regression analysis with adjustment for confounding factors was used to assess mortality after the incidence of functional disability in a spouse. RESULTS: The multivariate adjusted hazard ratio for mortality was 1.78 (95% confidence interval 1.52-2.08, P < 0.01) in those whose spouses had functional disabilities compared with those with spouses who did not have functional disabilities. The mortality was consistently higher, irrespective of age group or sex. CONCLUSIONS: These results imply that caregiver burden might increase stress responses and lead to increased mortality; therefore, enhancement of support systems, including long-term care, housing and livelihood support services, for those with disability and their spouses might be important for preventing deaths. Geriatr Gerontol Int 2019; 19: 774-779.

BACKGROUND: It has been noted that not only adverse psychosocial health effects but also mortality might increase for a person living with a spouse with cancer. This study examined the association between a partner's cancer diagnosis and mortality among a Japanese population. METHODS: In December 2006, a survey was conducted on participants aged 40 years or older who were residing in northeastern Japan. We identified couples using municipality-specific household ID numbers by searching public records and confirmed partner's cancer diagnosis after the baseline measurement using regional cancer registration information. After following up for a maximum of 4.0 years with the participants regarding mortality and emigration by reviewing the Residential Registry Record, we used Cox's proportional hazards regression to estimate the hazard ratio (HR) of all-cause mortality. RESULTS: We identified 25,938 participants (12,969 pairs) and included them in the analyses. A total of 1,308 (5.0%) participants had partners with a cancer diagnosis after baseline. The study found no association between a partner's cancer diagnosis and all-cause mortality; multivariable HRs of all-cause mortality for individuals in exposed subjects compared with those in unexposed subjects were 1.35 (95% confidence interval [CI] = 0.99-1.83; p = .055). Contrarily, sensitivity analyses of mortality attributed to having partners diagnosed with cancer based on the time since entry showed that all-cause mortality significantly increased only within one year from spouse cancer diagnosis; HR = 2.18 (95% CI = 1.44-3.30; p < .01). CONCLUSIONS: Our findings reveal that the mortality rate from partner's cancer diagnosis was significantly high during the early period of diagnosis and multidisciplinary teams for cancer treatment might be important for preventing death among the partner.

Cancer diagnosis influences both patients and their closest relatives. This cross-sectional study examined psychological distress among individuals whose partners had cancer in a population-based sample. Participants in the survey were citizens residing in Ohsaki City, Miyagi, Japan. Spouse pairs were identified by information of participants' relationship to the householder and address provided by municipality, and we collected self-report information on cancer history and current pain (but not the cause of pain). Psychological distress was evaluated using the Kessler 6 scale (K6). We identified 29,410 potential participants (14,705 couples), of which 23,766 (11,690 men and 12,076 women) were included in the analyses. A total of 1,374 participants (581 male and 793 female participants) had partners with history of cancer. Logistic regression analyses revealed that these participants, regardless of sex, did not show significantly higher risk of psychological distress (K6 score ≥ 13). When stratifying the analysis by partners' current pain, men whose partners had cancer and pain showed greater odds of psychological distress (odds ratio = 1.5, p = 0.04), compared with men whose partners had no cancer and had pain. However, male subjects whose partners had cancer but no pain did not show greater odds of psychological distress compared with men whose partners had no cancer and no pain. By contrast, in women whose partners had cancer, psychological distress was not associated with pain status. In conclusion, men whose partners had cancer and pain have higher risk of psychological distress, and its screening to these individuals may reduce the risk.

Objective: To examine the relative risk of psychological distress of men with prostate cancer and their partners during the period before and after prostate cancer diagnosis compared with men without prostate cancer and their partners. Methods: The participants reported questionnaires on psychological distress at four time points: before prostate cancer biopsy, and at 1, 3 and 6 months following prostate cancer diagnosis. We performed multiple logistic regression analyses to examine the relative risk of psychological distress. Results: A total of 115 couples answered the questionnaires at all four time points. Men with prostate cancer showed a significantly higher risk of psychological distress compared to men without prostate cancer at 1 (odds ratio [OR] = 4.8, 95% confidence interval [CI] = 1.9-13.1), 3 (OR = 3.2, 95% CI = 1.1-10.2) and 6 months following prostate cancer diagnosis (OR = 6.9, 95% CI = 2.3-25.7). Their partners showed a significantly higher risk of psychological distress compared to the partners of men without prostate cancer at 1 month following prostate cancer diagnosis (OR = 2.6, 95% CI = 1.1-6.6). Conclusions: Men with prostate cancer showed psychological distress during the 6 months following the cancer diagnosis. Their partners also showed psychological distress at 1 month following the cancer diagnosis. Inviting both men with prostate cancer and their partners to speak to their concerns, empathizing with them, finding the solutions together and monitoring of their psychological status regularly should be regarded as important following prostate cancer diagnosis.

Background/Aims: Dai-kenchu-to (DKT), a traditional Japanese herbal medicine, is known to increase gastrointestinal motility and improve ileal function. We tested our hypotheses that (1) pretreatment with DKT would block the colorectal distention-induced visceromotor response in rats, and (2) pretreatment with DKT would attenuate colorectal distention-induced adrenocorticotropic hormone (ACTH) release and anxiety-related behavior. Methods: Rats were pretreated with vehicle or DKT (300 mg/kg/5 mL, per os). Visceromotor responses were analyzed using electromyography in response to colorectal distention (10, 20, 40, 60, and 80 mmHg for 20 seconds at 3-minutes intervals). Anxiety-related behavior was measured during exposure to an elevated-plus maze after colorectal distention. Plasma ACTH and serum corticosterone levels were measured after exposure to the elevated-plus maze. Results: Colorectal distention produced robust contractions of the abdominal musculature, graded according to stimulus intensity, in vehicle-treated rats. At 40, 60, and 80 mmHg of colorectal distention, the visceromotor responses of DKT-treated rats was significantly lower than that of vehicle-treated rats. At 80 mmHg, the amplitude was suppressed to approximately one-third in DKT-treated rats, compared with that in vehicle-treated rats. Smooth muscle compliance and the velocity of accommodation to 60 mmHg of stretching did not significantly differ between the vehicle-treated and DKT-treated rats. Similarly, the DKT did not influence colorectal distention-induced ACTH release, corticosterone levels, or anxiety-related behavior in rats. Conclusions: Our results suggest that DKT attenuates the colorectal distention-induced visceromotor responses, without increasing smooth muscle compliance, ACTH release or anxiety-related behavior in rats.

OBJECTIVE: Although various factors thought to be correlated with anxiety in cancer patients, relative importance of each factors were unknown. We tested our hypothesis that personality traits and coping styles explain anxiety in lung cancer patients to a greater extent than other factors. METHODS: A total of 1334 consecutively recruited lung cancer patients were selected, and data on cancer-related variables, demographic characteristics, health behaviors, physical symptoms and psychological factors consisting of personality traits and coping styles were obtained. The participants were divided into groups with or without a significant anxiety using the Hospital Anxiety and Depression Scale-Anxiety, and a binary logistic regression analysis was used to identify factors correlated with significant anxiety using a multivariate model. RESULTS: Among the recruited patients, 440 (33.0%) had significant anxiety. The binary logistic regression analysis revealed a coefficient of determination (overall R(2)) of 39.0%, and the explanation for psychological factors was much higher (30.7%) than those for cancer-related variables (1.1%), demographic characteristics (2.1%), health behaviors (0.8%) and physical symptoms (4.3%). Four specific factors remained significant in a multivariate model. A neurotic personality trait, a coping style of helplessness/hopelessness, and a female sex were positively correlated with significant anxiety, while a coping style of fatalism was negatively correlated. CONCLUSIONS: Our hypothesis was supported, and anxiety was strongly linked with personality trait and coping style. As a clinical implication, the use of screening instruments to identify these factors and intervention for psychological crisis may be needed.

OBJECTIVE: Partners of prostate cancer patients have been reported to suffer from high levels of psychological distress, although there are few reports of the changes in their distress levels observed before and after the diagnosis and the factors influencing them. This study constructed a longitudinal psychosocial database of prostate cancer biopsy subjects and their partners. This paper describes a summary of the database and the nature and severity of the psychological distress and cancer-related worry. METHODS: We distributed self-administered questionnaires to subjects scheduled for a prostate cancer biopsy and their partners on four occasions: prior to the biopsy, and 1, 3 and 6 months after being informed whether the diagnosis was cancer or not. The questionnaires included questions pertaining to the psychological distress, cancer-related worry and correlational factors. RESULTS: Of the 240 couples who agreed to participate in the database project, 184 couples completed the first and second surveys; thus, the database consists of them. While no significant differences in the levels of psychological distress were found among the participants before the biopsy, the prostate cancer patients and their partners had significantly higher levels of psychological distress as compared with the non-prostate cancer patients at 1 month after being informed whether the diagnosis was cancer or not. CONCLUSIONS: This study constructed a longitudinal psychosocial database of prostate cancer biopsy subjects and their partners. Our findings suggest that partners of prostate cancer patients might experience a similar psychological impact to the prostate cancer patients before and after the diagnosis.

BACKGROUND: Patients with physical disease are known to suffer considerable psychological distress. Social support may confound the association between physical disease and psychological distress. Population-based epidemiological studies have not been conducted on the association between history of physical disease, psychological distress and social support. METHODS: Using cross-sectional data from 2006, we studied 43 487 community-dwelling people aged ≥40 years living in Japan. We examined the association between 13 self-reported histories of physical disease and psychological distress evaluated using the Kessler 6-item psychological distress scale (K6), defined as ≥13 points out of 24. To investigate the association, we performed multiple logistic regression analyses adjusted for age, gender, social support and possible confounders. Social support, as the interaction between physical disease and psychological depression, was tested through the addition of cross-product terms to the multivariate-adjusted model. RESULTS: The following histories of physical disease were found significantly and positively associated with psychological distress: cancer, diabetes mellitus, hyperlipidemia, hypertension, myocardial infarction, stroke, gastric or duodenal ulcer, liver disease, arthritis, osteoporosis, kidney disease and fall or fracture (odds ratio, 1.2-2.3). Social support did not modify the association between most histories of physical disease and psychological distress. CONCLUSIONS: Subjects with a history of physical disease were significantly and positively associated with psychological distress, and social support did not modify this association for most physical diseases. Even after patients have left hospital following treatment for physical disease, they require continuous monitoring for psychological distress by doctors and paramedics.

BACKGROUND: Previous studies suggest that spouses of cancer patients are at increased risk for several chronic diseases. We investigated mortality in relation to cancer morbidity in the stable female partner. METHODS: We established a national retrospective cohort study of 1,422,131 men who had lived continuously with the same partner for at least 5 years and used Cox regression analysis to assess the association between experiencing cancer in a cohabiting partner and all-cause mortality. RESULTS: The risk for death was only slightly elevated among men whose partner had cancer than for men whose partner remained free of cancer (hazard ratio = 1.03; 95% confidence interval = 1.01-1.05). CONCLUSIONS: Although a cancer diagnosis in a spouse might be associated with considerable distress, our study indicates that the risk for death differs only slightly between men living with a partner with cancer and those living with a partner without cancer.

BACKGROUND: Various risk factors for depression in lung cancer patients have been suggested but have been examined separately in studies with relatively small sample sizes. The present study examined the biopsychosocial risk factors of depression in lung cancer patients, focusing on psychological factors in the largest patient sample reported to date. PATIENTS AND METHODS: A total of 1334 consecutively recruited lung cancer patients were selected, and data on cancer-related variables, personal characteristics, health behaviors, physical symptoms, and psychological factors were obtained. The participants were divided into groups with or without depression using the Hospital Anxiety and Depression Scale. RESULTS: Among the recruited patients, 165 (12.4%) manifested depression. The results of a binary logistic regression analysis were significant (overall R2, 36.5%), and a greater risk for depression was strongly associated with psychological factors, such as personality characteristics (neuroticism) and coping style (low fighting spirit, helplessness/hopelessness, and anxious preoccupation). Although the contributions of cancer-related variables, personal characteristics, health behaviors, and clinical state were relatively low, cancer stage, cancer type, sex, and age correlated significantly with depression. CONCLUSION: Depression was most strongly linked with personality traits and coping style, and using screening instruments to identify these factors may be useful for preventive interventions.

Stress has been suggested to reduce survival after cancer, but the results of previous studies have been contradictory. We investigated the hypothesis in a national cohort of adults in Finland. Of those who completed the Stressful Life Events scale and the Stress of Daily Activities scale, 1470 and 1882, respectively, later had cancer and were included in the analysis, covering 23 years of follow-up between 1982 and 2004. In Cox regression analysis, the multivariate hazard ratio (HR) was 0.99 (95% confidence interval [CI], 0.96-1.01) for total number of life events and the HR for the life change score was 0.99 (95% CI, 0.95-1.03). Further, the HR was 0.92 (95% CI, 0.69-1.22) for severe daily stress. Overall, the results of the current study do not support the hypothesis that stress reduces cancer survival.

BACKGROUND: A few small studies published to date have suggested that major psychosocial problems develop in the partners of cancer patients; however, to the authors' knowledge, no studies to date have addressed their risk for severe depression. In a retrospective cohort study, the risk for hospitalization with an affective disorder of the male partners of women with breast cancer was investigated, using unbiased, nationwide, population-based information. METHODS: Followed were 1,162,596 men born between 1925 and 1973 who were aged ≥30 years at study entry, resided in Denmark between 1994 and 2006, had no history of hospitalization for an affective disorder, and had lived continuously with the same partner for at least 5 years. A Cox regression analysis included detailed clinical information regarding the diagnosis and treatment of breast cancer and on annually updated socioeconomic and health-related indicators obtained from national administrative and disease registers. RESULTS: During the 13 years of follow-up, breast cancer was diagnosed in the partners of 20,538 men. On multivariable analysis, men whose partner was diagnosed with breast cancer were found to be at an increased risk of being hospitalized with an affective disorder (hazards ratio, 1.39; 95%confidence interval, 1.20-1.61), with a dose-response pattern for the severity of breast cancer. Furthermore, men whose partner died after breast cancer had a significant, 3.6-fold increase in risk for an affective disorder when compared with men whose partner survived breast cancer. CONCLUSIONS: The results of the current study supported the hypothesis that men whose partner had breast cancer were at an increased risk for hospitalization with an affective disorder.

Personality traits have been studied extensively as risk and prognostic factors for cancer; however, the association remains unclear. This prospective, population-based cohort study comprised 59,548 Swedish (1974-1999) and Finnish (1976-2004) participants who completed a questionnaire eliciting information for the Eysenck Personality Inventory and on health behavior at baseline. To analyze the association of personality traits extraversion and neuroticism with risk of cancer, the authors identified 4,631 cancer cases for a maximum 30 years of follow-up. To assess the association with cancer survival among the Finnish participants, they identified 2,733 cancer cases and, later, 1,548 deaths for a maximum 29 years of follow-up. Hazard ratios were estimated by treating the personality scales as continuous variables and are presented per one increase in score on each scale. In multivariate analyses, extraversion and neuroticism were not significantly associated with risk of cancers at all sites (extraversion: hazard ratio = 0.99, 95% confidence interval: 0.98, 1.01; neuroticism: hazard ratio = 1.00, 95% confidence interval: 0.99, 1.02). Results showed no significant association between these traits and the hazard ratio for death after cancers at all sites, and they do not support the hypothesis that extraversion and neuroticism are direct risk factors for cancer or survival after cancer.

BACKGROUND: It has been hypothesized that personality traits affect survival after cancer, but studies have produced inconsistent results. This study examined the association between mental vulnerability and survival after cancer in Denmark in a prospective cohort study. METHODS: Between 1976 and 2001, 12733 residents of Copenhagen completed a questionnaire eliciting information on a 12-item mental vulnerability scale, as well as various personal data. Follow-up in the Danish Cancer Registry until 2003 identified 884 incident cases of primary cancer, and follow-up for death from the date of cancer diagnosis until 2003 identified 382 deaths. Mental vulnerability scores were divided into 4 approximately equal-sized groups. Cox proportional hazards regression models were used to estimate the hazard ratio (HR) of all-cause mortality. RESULTS: Multivariate HR for all-cause mortality for persons in the highest category of mental vulnerability compared with those at the lowest was 1.1 (95% confidence interval = 0.9-1.5). CONCLUSION: We found no support for the hypothesis that mental vulnerability is associated with survival after cancer diagnosis.

Gastroenteritis is one of the risk factors for developing irritable bowel syndrome (IBS). However, the precise mechanism of postinfectious IBS is still unknown. We tested the hypothesis that a combination of previous inflammation and repetitive colorectal distention (CRD) makes the colon hypersensitive and that treatment with a corticotropin-releasing hormone receptor 1 (CRH-R1) antagonist blocks this colonic hypersensitivity. Rats were pretreated with vehicle or 2,4,6-trinitrobenzene sulphonic acid (TNBS) 6 weeks before CRD. For the CRD experiment, the colorectum was distended once a day for six consecutive days. The CRH-R1 antagonist (CP-154,526, 20 mg kg(-1)) or vehicle was injected subcutaneously 30 min before CRD. Visceral perception was quantified as visceromotor response (VMR) using an electromyograph. For histological examination, the rats were killed on the last day of CRD experiment, and haematoxylin and eosin-staining of colon segments was performed. Although from the first to the third day of CRD, VMRs increased in both the vehicle-treated rats and TNBS-treated rats, they were significantly higher in TNBS-treated rats than those in vehicle-treated controls. On the fifth day of CRD, however, VMRs in the vehicle-treated rats were significantly greater than those in TNBS-treated rats. Pretreatment of rats with CP-154,526 significantly attenuated the increase in VMR induced by repetitive CRD with previous inflammation. Finally, we found that repetitive CRD and repetitive CRD after colitis induced visceral inflammation. These results indicate that a combination of previous inflammation and repetitive CRD induces visceral hypersensitivity and that a CRH-R1 antagonist attenuates this response in rats.

OBJECTIVE: Previous studies have suggested that marital status is associated with survival from lung cancer; however, its association is not conclusive. The association between marital status and survival in Japanese patients with non-small cell lung cancer (NSCLC) was prospectively investigated. METHODS: Between July 1999 and July 2004, a total of 1230 NSCLC patients were enrolled. The baseline survey consisted of the collection of clinical information and various demographic data, including marital status. A Cox regression model was used to estimate the hazards ratio (HR) of all-cause mortality adjustments for age, BMI, education level, performance status, histology type, clinical stage, smoking status, choice of definitive treatment, and depression. RESULTS: The multivariable adjusted HR of male widowed patients versus male married patients was 1.7 (95% confidence interval=1.2-2.5, p=0.005). However, no significant increased risk of death in female widowed patients compared with female married patients was observed (HR=0.7, 95% confidence interval=0.5-1.1, p=0.15). With regard to separated/divorced and single patients no significant increased risk of death in male and/or female compared with married patients was observed. CONCLUSIONS: The present data suggest that male widowed patients with NSCLC have a higher mortality rate than male married patients with NSCLC, after controlling for various factors.

We conducted a prospective cohort study in Japan to investigate associations between negative psychological aspects and cancer survival. Between July 1999 and July 2004, a total of 1178 lung cancer patients were enrolled. The questionnaire asked about socioeconomic variables, smoking status, clinical symptoms, and psychological aspects after diagnosis. Negative psychological aspects were assessed for the subscales of helplessness/hopelessness and depression. Clinical stage, performance status (PS), and histologic type were obtained from medical charts. The subjects were followed up until December 2004, and 686 had died. A Cox regression model was used to estimate the hazards ratio (HR) of all-cause mortality. After adjustment for socioeconomic variables and smoking status in addition to sex, age, and histologic type, both helplessness/hopelessness and depression subscales showed significant linear positive associations with the risk of mortality (p for trend<0.001 for both). However, after adjustment for clinical state variables in addition to sex, age, and histologic type, these significant linear positive associations were no longer observed (p for trend=0.41 and 0.26, respectively). Our data supported the hypothesis that the association between helplessness/hopelessness and depression and the risk of mortality among lung cancer patients was largely confounded by clinical state variables including clinical stage, PS, and clinical symptoms.

PURPOSE: To elucidate the current status of cancer rehabilitation in institutions nationwide. METHOD: A questionnaire survey regarding the current status of cancer rehabilitation in 1693 healthcare institutions was conducted by mail. The survey first asked whether rehabilitation was being conducted for cancer patients and, in facilities in which it was being conducted, it then asked about the content of the rehabilitation, the stage of the cancer patients, etc. Facilities in which cancer rehabilitation was not being conducted were surveyed in regard to whether there was a need for cancer rehabilitation. RESULTS: Valid replies were obtained from 1045 (62.0%) institutions and 864 (82.7%) of them conducted rehabilitation for cancer patients. A high proportion of the content of the rehabilitation was found to be related to physical function. Activities of daily living guidance and training were also found to be conducted in a high proportion. Low proportions of the facilities conducted content that was specialized for cancer. Of the 181 facilities in which rehabilitation was not being conducted for cancer patients, 171 (94.5%) replied that they felt that rehabilitation was needed for cancer patients. CONCLUSIONS: Based on the results of this fact-finding survey it will be necessary to consider strategies for popularizing and developing rehabilitation programmes for cancer patients in Japan.

We conducted a population-based prospective cohort study in Denmark to investigate associations between the personality traits and cancer survival. Between 1976 and 1977, 1020 residents of the Copenhagen County completed a questionnaire eliciting information on personality traits and various health habits. The personality traits extraversion and neuroticism were measured using the short form of the Eysenck Personality Inventory. Follow-up in the Danish Cancer Registry for 1976-2002 revealed 189 incidents of primary cancer and follow-up for death from the date of the cancer diagnosis until 2005 revealed 82 deaths from all-cause in this group. A Cox proportional-hazards model was used to estimate the hazard ratios (HRs) of death from all-cause according to extraversion and neuroticism adjusting for potential confounding factors. A significant association was found between neuroticism and risk of death (HR, 2.3 (95% CI=1.1-4.7); Linear trend P=0.04) but not between extraversion and risk of death (HR, 0.9 (0.4-1.7); Linear trend P=0.34). Similar results were found when using cancer-related death. Stratification by gender revealed a strong positive association between neuroticism and the risk of death among women (Linear trend P=0.03). This study showed that neuroticism is negatively [corrected] associated with cancer survival. Further research on neuroticism and cancer survival is needed.

BACKGROUND: The lung cancer database project was established in 1999 at the National Cancer Center Hospital East, Japan, as an ongoing project to integrate data on various factors in lung cancer patients. The aim of the project was to construct a large-scale cancer registry for lung cancer that would contribute to basic research and clinical research in the future. METHODS: Between July 1999 and July 2004, consecutive lung cancer patients were recruited into this project. The baseline survey consisted of self-administered questionnaires concerning various demographic data, health habits and psychological factors. Medical information was obtained from the patients' medical charts. Urine specimens and blood samples were collected, and DNA was extracted from blood lymphocytes. RESULTS: Out of the 2506 patients who were asked to participate in the project, 2036 (81%) patients with newly diagnosed, untreated primary lung cancer were enrolled. The final analytic cohort consisted of 1995 patients. Virtually all of the 1995 patients (corresponding rate, 99%) completed the questionnaires on demographic data and health habits. The corresponding rates for the questionnaires on psychological factors and dietary habits were 99 and 94%, respectively. In a follow-up survey conducted to determine vital status as of December 2004, a total of 1051 patients (53%) had died and 44 patients (2%) were lost to follow-up. CONCLUSIONS: This paper overviews the rationale for initiating the lung cancer database project, Japan. This database should prove useful for researchers examining the pathogenesis of lung cancer and may contribute to the formulation of a framework for cancer treatment.

Psychological depression is thought to be a predictor of poor survival among cancer patients. The objective of the present study was to investigate the association between depression and survival in surgically treated Japanese patients with non-small cell lung cancer (NSCLC). From June 1996 through April 1999, a total of 229 patients with postoperative lung cancer were enrolled. Three months after the patients' surgery, the Structured Clinical Interview for DSM-III-R (SCID) and the Profile of Mood States (POMS) were used to assess the patient for depression, based on the interviewers' rating and a self-report, respectively. The follow-up period consisted of a total of 14 342 person-months (median=69 months). As of January 2004, 55 deaths had occurred within the follow-up period. A Cox regression was used to estimate the hazard ratio (HR) of mortality adjusting for age, sex, smoking status, occasion of diagnosis, pathological stage and preoperative percentage forced expiratory volume in 1 s. The depression-dejection subscale on the POMS was divided into three score levels. The multivariate HR of survival for individuals with depression, as diagnosed by the SCID, was 2.2 (95% confidence interval 0.8-6.0) (P-value=0.14), compared with individuals without depression. The multivariate HR of survival for subjects in the highest level of the POMS Depression-Dejection subscale was 1.4 (0.7-2.6), compared with in the lowest level (trend P-value=0.0502). This prospective cohort study in Japan does not support the hypothesis that depression is associated with survival among NSCLC patients after curative resection, but further analysis involving a long-term follow-up period is needed.

It has been suggested that marital status and social support are associated with survival in cases of lung cancer, and that such an association may be mediated by several factors. In this prospective cohort study, we investigated the effect of marital status and social support on survival after curative resection for non-small cell lung carcinoma (NSCLC) in Japan. From June 1996 to April 1999, a total of 238 patients with resectable NSCLC were enrolled. Marital status and social support were assessed. The presence and absence of confidants and the satisfaction level with the confidants were used as factors reflecting social support. During the follow-up period, 57 deaths from all causes were identified through January 2004. For the statistical analysis, Cox proportional hazards regression analyses were used. With regard to marital status, the multivariable adjusted hazard ratio (HR) of unmarried patients versus married patients was 0.8 (95% confidence interval, 0.3-1.8) (P-value=0.53) after controlling for potential confounding factors, including age, sex, occasion of cancer diagnosis, pathological stage, smoking status, smoking status after surgery and serum albumin level. Similarly, the multivariable adjusted HR of patients without confidants versus those with confidants was 1.0 (0.5-2.2) (P-value=0.90), whereas the multivariable adjusted HR of the dissatisfied-with-confidants group versus the satisfied-with-confidants group was 0.7 (0.4-1.3) (P-value=0.28). The present data do not support the hypothesis that marital status and social support are associated with survival in NSCLC.

OBJECTIVE: The objective of this study was to verify the hypothesis that variation of the serotonin transporter gene promoter region (5-HTTLPR) is associated with sensitivity to stress. METHODS: Genotyping of 5-HTTLPR and evaluation of emotional states were performed on 194 participants. Participants' emotional states were evaluated using the Perceived-Stress Scale (PSS), the State-Trait Anxiety Inventory (STAI), and the Self-rating Depression Scale (SDS). RESULTS: There was significant GenderxGenotype interaction in STAI (state, P<.05; trait, P<.05). Females with the l/s genotype showed higher anxiety than those with the s/s genotype in both state and trait anxiety. Oppositely, males with the s/s genotype showed higher anxiety than those with the l/s genotype. CONCLUSION: On all emotional scales, females with the l/s genotype showed high scores, contrary to males with the same genotype. Therefore, our results suggest that 5-HTTLPR l allele may be one pathway that activates negative emotion in females but acts contrary in males.

BACKGROUND & AIMS: The corticotropin-releasing hormone receptor 1 mediates stress-induced changes in colonic motor activity and emotion. We tested the hypothesis that pretreatment with JTC-017, a specific corticotropin-releasing hormone receptor 1 antagonist, blocks colorectal distention-induced hippocampal noradrenaline release and visceral perception in rats. We also investigated whether pretreatment with JTC-017 blocks acute or chronic colorectal distention-induced adrenocorticotropic hormone release, anxiety, and stress-induced changes in colonic motility. METHODS: Rats were pretreated intrahippocampally with alpha-helical corticotropin-releasing hormone (1.25 microg/kg; vehicle), a nonspecific corticotropin-releasing hormone receptor antagonist, or intraperitoneally with JTC-017 (10 mg/kg). Hippocampal noradrenaline release after microdialysis and the frequency of abdominal contractions were measured in response to acute colorectal distention. Plasma adrenocorticotropic hormone levels, anxiety-related behavior, and stress-induced changes in colonic motility were evaluated after acute or chronic colorectal distention followed by exposure to an elevated plus maze. RESULTS: Administration of alpha-helical corticotropin-releasing hormone or JTC-017 significantly attenuated hippocampal noradrenaline release and reduced the frequency of abdominal contractions induced by acute distention. In addition, JTC-017 significantly reduced plasma adrenocorticotropic hormone and anxiety after acute distention. After chronic distention, changes in plasma adrenocorticotropic hormone and anxiety were not significant because of habituation. In contrast, a significant increase in fecal pellet output during the elevated plus maze was observed after chronic distention. This increase in fecal pellet output was blocked by pretreatment with JTC-017. CONCLUSIONS: Our results suggest that JTC-017, a specific corticotropin-releasing hormone receptor 1 antagonist, attenuates hippocampal noradrenaline release, visceral perception, adrenocorticotropic hormone release, and anxiety after acute colorectal distention in rats. In addition, JTC-017 blocks stress-induced changes in colonic motility after chronic colorectal distention in rats.

We tested the hypothesis that personality plays a role in cancer outcome in a population-based prospective cohort study in Japan. In July 1990, 41 442 residents of Japan completed a short form of the Eysenck Personality Questionnaire-Revised and a questionnaire on various health habits, and between January 1993 and December 1997, 890 incident cases of cancer were identified among them. These 890 cases were followed up until March 2001, and a total of 356 deaths from all causes was identified among them. Cox proportional-hazards regression was used to estimate the hazard ratio (HR) of death according to four score levels on each of four personality subscales (extraversion, neuroticism, psychoticism, and lie), with adjustment for potential confounding factors. Multivariable HRs of deaths from all causes for individuals in the highest score level on each personality subscale compared with those at the lowest level were 1.0 for extraversion (95% CI=0.8-1.4; Trend P=0.73), 1.1 for neuroticism (0.8-1.6; Trend P=0.24), 1.2 for psychoticism (0.9-1.6; Trend P=0.29), and 1.0 for lie (0.7-1.5; Trend P=0.90). The data obtained in this population-based prospective cohort study in Japan do not support the hypothesis that personality is associated with cancer survival.

We tested our hypothesis that noradrenaline is released in the hippocampus by colorectal distention of rats, and that it induces pain-related behavior. Noradrenaline levels with colorectal distention were significantly higher than those with restraint stress and free moving. Abdominal contractions were induced only by colorectal distention. Our results suggest that noradrenaline levels increase in the hippocampus under colorectal distention and this may relate to behavioral changes.