Structural and Computational Analyses of the Unique Interactions of Opicapone in the Binding Pocket of Catechol O-Methyltransferase: A Crystallographic Study and Fragment Molecular Orbital Analyses.

A third-generation inhibitor of catechol O-methyltransferase (COMT), opicapone (1), has the 3-nitrocatechol scaffold as do the second-generation inhibitors such as entacapone (2) and tolcapone (3), but only 1 can sustainably inhibit COMT activity making it suitable for a once-daily regimen. These improvements should be attributed to the optimized sidechain moiety (oxidopyridyloxadiazolyl group) of 1 substituted at the 5-position of the 3-nitrocatechol ring. We analyzed the role of the sidechain moiety by solving the crystal structures of COMT/S-adenosylmethionine (SAM)/Mg/1 and COMT/S-adenosylhomocysteine (SAH)/Mg/1 complexes. Fragment molecular orbital (FMO) calculations elucidated that the dispersion interaction between the sidechains of Leu 198 and Met 201 on the ß6ß7-loop and the oxidopyridine ring of 1 were unique and important in both complexes. In contrast, the catechol binding site made a remarkable difference in the sidechain conformation of Lys 144. The ε-amino group of Lys 144 was outside of the catalytic pocket and was replaced by a water molecule in the COMT/SAH/Mg/1 complex. No nitrocatechol inhibitor has ever been reported to make a complex with COMT and SAH. Thus, the conformational change of Lys 144 found in the COMT/SAH/Mg/1 complex is the first crystallographic evidence that supports the role of Lys 144 as a catalytic base to take out a proton ion from the reaction site to the outside of the enzyme. The fact that 1 generated a complex with SAH and COMT also suggests that 1 could inhibit COMT twofold, as a typical substrate mimic competitive inhibitor and as a product-inhibition enhancer.

Persistence of Mental Health Deterioration Among People Living Alone During the COVID-19 Pandemic: A Periodically-repeated Longitudinal Study.

BACKGROUND: This longitudinal study aimed to investigate how psychological distress levels changed from early to middle phases of the new coronavirus (COVID-19) pandemic depending on the living arrangements of individuals. METHODS: An internet-based, longitudinal survey of 2,400 Japanese people was conducted every 5-6 weeks between February 2020 and January 2021. The presence of severe psychological distress (SPD) was measured using the Kessler's psychological distress scale. Living arrangements were classified into two groups (ie, living alone or living with others). Mixed-effects logistic regression analysis was performed to assess whether changes in SPD status were different depending on living arrangements. RESULTS: Of 2,400 respondents, 446 (18.5%) lived alone. Although the proportion of SPD in both individuals living alone and those living with others increased to the same extent in the early phase of the pandemic, the distress levels decreased after the early phase of the pandemic in the group living with others, compared with the group living alone, for which SPD remained high. The odds ratio (OR) of developing SPD in interaction term with survey phases tended to be higher among those who lived alone than those who lived with others in Phase 6 (OR 1.89; 95% confidence interval [CI], 0.99-3.64) and Phase 7 (OR 1.88; 95% CI, 0.97-3.63). CONCLUSION: During the COVID-19 pandemic, those living alone are persistently at a higher risk of SPD compared to those living with others. Effective countermeasures targeting those living alone, such as enhancing online communication or providing psychological therapies, are essential.

Objectively Measured Intensity-specific Physical Activity and Hippocampal Volume Among Community-dwelling Older Adults.

BACKGROUND: The hippocampus is a brain structure important for memory and cognitive function. Physical activity may help prevent hippocampal atrophy. However, few studies have measured sedentary behavior (SB) and intensity-specific physical activity using an accelerometer. This study aimed to examine the cross-sectional associations of objectively-determined SB, light-intensity physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) measured by an accelerometer with hippocampal volume among community-dwelling older adults using compositional data analysis (CoDa) approach. METHODS: This cross-sectional study was part of the Neuron to Environmental Impact across Generations (NEIGE) study. A randomly recruited sample of 485 Japanese older adults (47% male; aged 65-84 years) wore tri-axial accelerometers (Omron Healthcare) for 7 consecutive days in 2017. Hippocampal volume was measured with magnetic resonance imaging and the left and right hippocampal volumes were automatically segmented using FreeSurfer software. Associations of sedentary and physically active behaviors with hippocampal volume were examined with compositional linear regression analysis based on isometric log-ratio transformations of time use adjusted for potential confounding factors. RESULTS: The relative proportion of time spent in MVPA, compared to the other two activities, was significantly positively associated with right hippocampal volume (ß: 57.1, P-value = 0.027). However, no association existed between higher proportions of MVPA and left hippocampal volume, or between proportions of SB or LPA with either left or right hippocampal volumes. CONCLUSION: The proportion of time spent in MVPA, relative to the other two activities, was significantly positively associated with right hippocampal volume. MVPA may be beneficial for maintaining hippocampal volume.

Crystal Structure of Catechol O-Methyltransferase Complexed with Nitecapone.

Catechol O-methyltransferase (COMT) is known as an important drug-target protein in the field of Parkinson's disease. All clinically approved COMT inhibitors bring a 5-substituted-3-nitrocatechol ring as a pharmacophore, and they bind to COMT with S-adenosylmethionine (SAM) and an Mg2+ ion to form a quaternary complex (COMT/SAM/Mg2+/inhibitor). However, structural information about such quaternary complexes is only available for a few inhibitors. Here, a new crystal structure of COMT complexed with nitecapone (5), SAM and Mg2+ is revealed. Comparison of the structures of these complexes indicates that conformation of the catechol binding pocket is almost constant regardless of structure of the inhibitors. The only restriction of the side chain of inhibitors (i.e., the substituent at the 5-position of 3-nitrocatechol) seems to be that it does not make steric repulsion with COMT. However, recent crystallographic and biochemical studies suggest that COMT is a flexible protein, and its conformational flexibility seems crucial for its catalytic process. Based on this information, implications of these quaternary inhibitor complexes were investigated. Met 40 in the α2α3-loop makes atomic contacts with SAM or S-adenosylhomocysteine and the 3-position of the catechol inhibitor. This interaction seems to play a critical role in the affinity of the inhibitor and to stabilize the COMT/SAM/Mg2+/nitrocatechol inhibitor complex by fixing the flexible α2α3-loop.

Is objectively measured light-intensity physical activity associated with health outcomes after adjustment for moderate-to-vigorous physical activity in adults? A systematic review.

BACKGROUND: An increasing number of studies have demonstrated that light-intensity physical activity (LPA) confers health benefits after adjustment for moderate-to-vigorous physical activity (MVPA). The purpose of this systematic review was to summarize existing epidemiological evidence on associations of objectively measured LPA with health outcomes in adults. METHODS: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched on PubMed, Web of Science, CINAL, and Cochrane Library for articles analyzing the association between objectively determined LPA and health outcomes that were published up to January 2017. Data were extracted regarding authors, publication year, country of survey, study setting, number of participants, study design, physical activity (PA) assessment (type of accelerometer and intensity), health outcomes, confounders, and results (summary measures and association). A coding system was used to summarize the results. RESULTS: Of the 3254 studies identified, 24 cross-sectional and 6 longitudinal studies were included in this review. Most of the studies targeted the Western population. LPA was inversely associated with all-cause mortality risk and associated favorably with some cardiometabolic risk factors including waist circumference, triglyceride levels, insulin, and presence of metabolic syndrome. Only a small amount of data were available on mental health and cognitive function. CONCLUSIONS: LPA appears to be beneficially associated with important health outcomes after adjustment for MVPA in the adult population. Although current global PA guidelines recommend only MVPA, promoting LPA may confer additional health benefits.

Lower youth steps/day values observed at both high and low population density areas: a cross-sectional study in metropolitan Tokyo.

BACKGROUND: Physical activity among children and adolescents (collectively, youth) is important to ensure adult health. Population density is a factor that affects physical activity via various environmental factors. However, the relationship between population density and physical activity among youth is not fully understood, especially in extremely high density area. The aim of this study was to examine the relationship between population density and physical activity of youth using pedometer-determined step data. METHODS: A total of 13,688 youth between 6 to 15 years of age were identified from the 2011 Tokyo Metropolitan Survey of Physical Fitness, Physical Activity and Lifestyle. Participants were divided into five subgroups according to the population density of their municipality of residence. The population density's fixed effects on in-school, out-of-school, and daily total step count adjusted for gender and school grade were estimated. RESULTS: The lowest (< 2500 people/km2) and highest (> 10,000 people/km2) population density subgroups had significantly lower daily total step count and out-of-school step count than those of the reference population (5000-7500 people/km2). In contrast, in-school step count did not significantly differ according to population density. CONCLUSIONS: Both low population density and also high population density were related to lower step count. Low physical activity in high density areas has not been well documented in previous research. Considering population growth in urbanized area globally, these results suggest the importance of continued research of physical activity determinants in high population density areas.

Identification of Two Phenanthrene Derivatives from Australasian Allied Species in Genus Dendrobium.

Genus Dendrobium (Orchidaceae) contains numerous species. Phylogenetic analyses based on morphological characteristics and DNA sequences indicated that this genus is divided into two major groups: Asian and Australasian clades. On the other hand, little is known about the phytochemical differences and similarities among the species in each clade. In this study, we selected 18 Dendrobium species (11 from the Asian clade and 7 from the Australasian clade) and constructed HPLC profiles, arrays composed of relative intensity of the chromatographic peaks. Next, orthogonal partial least square discriminant analysis (OPLS-DA) was applied to the profile matrix to classify Dendrobium species into the Asian and Australasian clades in order to identify the peaks that significantly contribute to the class separation. In the end, two phenanthrenes, 4,9-dimethoxyphenanthrene-2,5-diol 1 and 1,5-dimethoxyphenanthrene-2,7-diol 2, which contributed to the class separation, were isolated from the HPLC peaks. The existence of 2 was limited to the genetically related Australasian species.

[Descriptive epidemiology of accelerometer-measured moderate to vigorous physical activity in Japanese older adults].

AIM: Most physical activity (PA) guidelines for health promotion recommend moderate to vigorous PA (MVPA) lasting at least 10 minutes (long-bout MVPA). However, recent studies have shown the beneficial effects of short-bout MVPA (intermittent and lasting <10 minutes). Therefore, we aimed to clarify the detailed patterns of MVPA of community-dwelling older adults using accelerometers. METHODS: This is a cross-sectional descriptive study. Community-dwelling older Japanese adults (total: 1,210; 70-80 years of age) randomly selected from residential registries of 3 municipalities (Bunkyo, Fuchu, and Oyama) were asked to wear an accelerometer (HJA-350 IT; Omron Healthcare, Japan). MVPA was classified by bout length (1-4, 5-9, 10-19, 20-29, and > 30 minutes). The mean frequency and duration of MVPA by each bout length and the proportion of long-bout MVPA were described. RESULTS: Valid data were obtained from 450 participants (men: 56.7%; mean age: 74 years). The mean±standard deviation of the frequency and duration of MVPA bouts were 21.8±14.6 times/day and 2.1±0.9 min, respectively. The total duration of MVPA was 46.5±33.0 min/day. Long-bout MVPA accounted for 26.9%±23.5% of daily MVPA, whereas MVPA of 1-4 minutes accounted for 43.4%. CONCLUSIONS: Older adults performed about 45 minutes of MVPA a day, but most of this was short-bout MVPA, which is overlooked by current WHO PA guidelines. In particular, short-bout MVPA was frequent among older women and those living in rural areas.

Light and sporadic physical activity overlooked by current guidelines makes older women more active than older men.

BACKGROUND: Men are generally believed to be more physically active than women when evaluated using current physical activity (PA) guidelines, which count only moderate-to-vigorous physical activity (MVPA) in bouts lasting at least 10 min. However, it remains unclear men are truly more physically active provided that all-intensity PA are evaluated. This population based cross-sectional study aimed to examine gender differences in patterns of objectively-assessed PA in older adults. METHODS: One thousand two hundred ten community-dwelling Japanese older adults who were originally randomly selected from residential registry of three municipalities were asked to respond a questionnaire and wear an accelerometer (HJA-350IT, Omron Healthcare). The prevalence of achieving current PA guidelines, ≥150 min/week MVPA in bouts lasting at least 10 min, was calculated. Gender differences in volume of each-intensity activity (METs-hour) were assessed by analysis of covariance after adjustment for age and wear time. RESULTS: Data from 450 (255 men, mean 74 years) participants who had valid accelerometer data were analyzed. Women were less likely to meet the guidelines (men: 31.0, women: 21.5%; p < 0.05). However, women accumulated more light-intensity PA (LPA) and short-bout (1-9 min) MVPA, and thus established higher total volume of PA (men: 22.0 METs-hour/day, women: 23.9 METs-hour/day) (p < 0.05). CONCLUSIONS: Older women were less active when evaluated against current PA guidelines, but more active by total PA. Considering accumulated evidence on health benefits of LPA and short-bout MVPA, our findings highlight the potential for the limitation of assessing PA using current PA guidelines.

Stereospecific inhibition of nitric oxide production in macrophage cells by flavanonols: Synthesis and the structure-activity relationship. Part 2.

To explore the structure-activity relationships of flavanonols on the inhibition of nitric oxide (NO) production in RAW 264.7 cells, we have prepared a series of synthetic flavanonols. In our previous study, the 2',3'-dihydroxyphenyl substructure was found to be the most potent B ring substructure among the flavanonols having 3,5,7-trihydroxychroman-4-one as the A/C ring. In this study, we examined the effect of diverse substitutions on the A ring of the 2-(2,3-dihydroxyphenyl)-3-hydroxychroman-4-one scaffold, i.e., by fixing the B ring to the 2',3'-dihydroxyphenyl substructure. Eighteen stereoisomers and 4 racemic mixtures were prepared, and their inhibitory potency on NO production in RAW 264.7 cells was tested. We observed higher inhibitory activity in the (2R,3R) stereoisomers than in the (2S,3S) stereoisomers. The presence of a hydroxy or a methoxy group at the 7-postiion enhanced the inhibitory potency, and the additional substitutions at the 6- or 8-position in the A ring increased potency and stereospecificity. A representative compound, (2R,3R)-2',3',7,8-tetrahydroxyflavanonol 5e, had an IC50 value of 17µM, whereas its (2S,3S) stereoisomer did not inhibit NO production at all at a concentration of 100µM. In this study, it was necessary to determine the absolute configuration of the stereoisomers of the synthesized flavanonols that carry methoxy substitutions in the A ring. The procedure to determine their absolute configuration by the CD excitation chirality method is also discussed.

Structure-activity relationship of the inhibitory effects of flavonoids on nitric oxide production in RAW264.7 cells.

We isolated flavonoids from herbal specimens from the Tibetan region (Sophora yunnanensis and Rhodiola sacra) that suppress nitric oxide (NO) production in macrophages stimulated by lipopolysaccharide and interferon-γ. The isolated flavonoids carry symmetric substitutions in the B ring (R3'=R5'). We analyzed the quantitative structure-activity relationship of the inhibitory activity by comparative molecular field analysis (CoMFA) using this series of flavonoids. Use of flavonoids with symmetrical substitutions in the B ring made it simpler to align molecules because it was not necessary to consider a huge number of combinations due to the B-ring conformation. The CoMFA model, whose cross-validated q2 value was 0.705, suggested the existence of a hydroxy group at the 5-position, the choice of the A/C-ring scaffold (chromane or chromene) and electrostatic field around the B ring are important for NO inhibitory activity. Flavonoids synthesized based on the CoMFA model exhibited significant inhibitory potential against NO production, validating the predictive capability of the CoMFA model.

Organizational justice and insomnia: a prospective cohort study examining insomnia onset and persistence.

PURPOSE: Insomnia is one of the most common health problems and causes a large social burden. Psychosocial work-related factors are reported to be associated with both insomnia onset and insomnia persistence. However, the association between organizational justice (OJ) and insomnia remains unclear. The objective of this study was to examine the effect of OJ on insomnia persistence, as well as insomnia onset. METHODS: A prospective cohort study with a 1-year observational period was conducted. Self-reported questionnaire data from 1588 employees were analyzed. OJ was measured using the Japanese version of the OJ questionnaire, which has four components (distributive, procedural, interpersonal, and informational). Insomnia was assessed with the Athens Insomnia Scale. Logistic regression analysis was used to explore the effects of OJ on insomnia. RESULTS: Among non-insomniac subjects at the baseline (n = 1236), low overall OJ was a risk of insomnia onset even after adjustment for lifestyle and work-related variables (adjusted odds ratio 0.66; 95% confidence interval 0.51-0.85). The procedural, interpersonal, and informational justice components were also associated with insomnia onset. Among insomniac subjects at the baseline (n = 352), low overall OJ, as well as the procedural and interpersonal justice components, was associated with insomnia persistence. Although these associations became insignificant after adjustment, the interpersonal justice component showed a marginally significant association with insomnia persistence (p = 0.058). CONCLUSIONS: OJ, especially interpersonal justice, was revealed as an associated factor for both insomnia onset and persistence. These findings may provide useful information for prevention of insomnia among working population.

A cross-sectional study of the association between city scale and daily steps in Japan: Data from the National Health and Nutrition Survey Japan (NHNS-J) 2006-2010.

Objective There is little evidence showing that inhabitants of urban areas engage in more physical activity than do rural ones, although accumulating evidence concerning the best neighborhood environments conducive to physical activity supports the idea. This study sought to fill the research gap by examining the association between city scale and daily steps using data from Japan's National Health and Nutrition Survey (NHNS).Methods We analyzed data from 15,763 men and 18,479 women aged 20 years and older who participated in a one-day pedometer measurement during any part of the NHNS between 2006 and 2010. The data obtained for these years were combined into a single data set. City scale was categorized into 5 groups based on population: 1) 12 large cities and 23 wards, 2) population greater than 150,000, 3) population 50,000-150,000, 4) population less than 50,000, and 5) towns and villages. Differences in daily steps among city scale groups were analyzed using an ANCOVA, adjusting for age by gender. The Bonferroni method was employed for multiple comparisons, and linear regression was used to test for linear trends. Subgroup analyses were performed by age (20-39, 40-64, older than 64), and job status. The study was approved by the Tokyo Medical University ethics committee, and use of these data complied with the Statistics Act of Japan.Results The steps per day for men after adjusting for age were Group 1 : 7,494±4,429 (mean±SD), Group 2 : 7,407±4,428, Group 3 : 7,206±4,428, Group 4 : 6,911±4,428, and Group 5 : 6,715±4,429. Women's daily steps according to city scale group were 6,767±3,648, 6,386±3,647, 6,062±3,646, 6,069±3,649, and 6,070±3,649 for Groups 1 through 5, respectively. There were overall statistically significant differences (ANCOVA, P<0.001) between both genders. The larger the city scale, the more mean daily steps that were taken by both men and women (P values for both trends <0.001). Subgroup analyses revealed significant differences in the mean daily steps by city scale, regardless of age or job status for both genders. There were no significant differences among Groups 3, 4, or 5 among unemployed men, men older than 64, or overall women, which differed from the results for men with jobs, who took fewer steps in smaller cities.Conclusions Our study showed that men and women living in larger cities took more steps compared to those living in smaller cities. Subgroup analyses further revealed that the associations between city scale and physical activity differed according to gender, age, and job status.

Stereospecific inhibition of nitric oxide production in macrophage cells by flavanonols: Synthesis and the structure-activity relationship.

To explore the structure-activity relationships on the inhibitory activity of flavanonols against nitric oxide (NO) production in inflammatory cells, we synthesized 19 flavanonols which shared a common 3,5,7-trihydroxychroman scaffold. A range of substitutions was included in the B ring in order to investigate the structure-activity relationship. We also succeeded in isolating stereoisomers from 16 of the flavanonols using chiral column chromatography. The inhibitory effects of these compounds on NO production were examined in RAW 264.7 cells (a murine macrophage-like cell line), which were activated by lipopolysaccharide (LPS). We only observed inhibitory activity against NO production in (2R,3R) stereoisomers, while the inhibitory activities of (2S,3S) stereoisomers were significantly weaker. We also evaluated the free radical scavenging potential of the flavanonols using 1,1-diphenyl-2-picrylhydrazyl (DPPH). Each stereoisomer indicated the equivalent DPPH scavenging potential as expected. The radical scavenging activity was not correlated with the inhibitory activity against NO. The inhibition of NO production by flavanonols is stereospecific and cannot simply be explained by their radical scavenging activity. We propose the possible existence of a 'target' molecule for flavanonols which is involved in the production and/or regulation of NO in RAW 264.7 cells.

Gender differences in association between psychological distress and detailed living arrangements among Japanese older adults, aged 65-74 years.

PURPOSE: Past studies have shown that living alone is detrimental to older adults' mental health. However, there has been little focus on how older adults' psychological distress differed by more detailed living arrangement, as well as by gender. The present study investigates various living arrangements in association with psychological distress among older men and women. METHODS: Data from community-dwelling Japanese older adults were collected through a mail survey (n = 1,807, aged 65-74 years, 51.5 % men). Psychological distress level was measured using Kessler's six-item psychological distress scale. Living arrangements were categorized into four groups; "living with spouse only", "living with spouse and other family", "living with other family without spouse" or "living alone". Multiple logistic regression analyses were used to examine the associations of living arrangements with psychological distress level. RESULTS: Older adults living alone were observed to have higher psychological distress. In addition, gender-stratified analyses showed that higher distress levels were observed among older men living with family, but without a spouse (OR: 2.85, 95 % CI: 1.51-5.39). In contrast, higher distress was observed among older women living with spouse and other family (OR: 1.53, 95 % CI: 1.03-2.28). CONCLUSIONS: Psychological distress in older Japanese adults was associated with living arrangements, but such associations differed by gender. The association of living with a spouse on older men's mental health was striking, while living with any family was found to be rather important for older women, aged 65-74 years.

[Commute mode - physical activity and the possibility of change to active commuting among Japanese workers: a descriptive study by region].

OBJECTIVES: Changing the mode of commuting from nonactive by car or motorcycle to active by walking, cycling, or public transport is expected to benefit health. However, the proportion of nonactive commuters who can change their commute mode to active forms remains unclear. The aim of this study was to determine the proportions of nonactive commuters and of those who can change their commute mode to an active form in various regions in Japan. METHODS: In this descriptive study, data were used from an online survey conducted from April to May 2021. Participants included 3,000 adults (20 to 79 years), who were registered with an online survey company. Workers were asked their means of transportation to work and commuting time. Workers using a car or motorcycle for more than 1 minute for commuting were defined as nonactive commuters, and the others were defined as active commuters. Then, nonactive commuters were asked about the possibility of changing their commute mode to active commuting (0%-100%, 11 options in 10% increments). The possibility of change was classified into four groups, i.e., impossible (0%), difficult (10%-40%), probably possible (50%-90%), and possible (100%). The proportions of nonactive commuters and nonactive commuters who can transition to active commuting were described by region. RESULTS: A total of 2,683 participants answered the survey, including 1,647 workers, of whom 1,551 were commuters. The nonactive commuters accounted for 41.4% of commuters overall. The proportion of nonactive commuters was higher in rural than in urban regions. The proportion of nonactive commuters who could change their commute mode was 32.9% of the nonactive commuters or 12.8% of all workers. Among the nonactive commuters, the proportion who could change their commute mode was higher in urban than in rural regions. Of the total workers, the proportion of nonactive commuters who could change their commute mode was higher in rural regions. CONCLUSION: Nonactive commuters accounted for 41.4% of all commuters. The proportion of nonactive commuters who could change their commute mode among nonactive commuters was higher in urban regions. However, in rural regions, as the proportion of nonactive commuters was high, the proportion of nonactive commuters who could change their commute mode among total workers was also high. These results suggest that some of nonactive commuters can change their commute mode from nonactive to active commuting, in rural as well as in urban regions.

Association between the Decrease in Medical Visit Frequency and Chronic Disease Worsening in the Early Stages of COVID-19 - A Longitudinal Study.

Objective This longitudinal study aimed to clarify the changes in the medical treatment behavior of Japanese patients with chronic diseases during the early phase of the coronavirus disease 2019 (COVID-19) pandemic and examine the factors associated with disease worsening. Methods Subjects with chronic diseases were selected from a panel survey that started at the beginning of the COVID-19 pandemic consists of 2,400 participants recruited via the Internet. Medical treatment behaviors (decrease in medical visit frequency, inability to take regular medications, and utilization of telephone/online medical care), psychological distress, and sociodemographic factors were evaluated at baseline (May 2020) and at the follow-up survey (February 2021). A worsening of chronic diseases was defined as those who answered "yes" to the question, "Has-the-condition-of-the-chronic-disease-worsened?". The factors related to the worsening of chronic diseases at follow-up were examined. Results A total of 514 participants (mean age 61.6±12.9 years) were analyzed. The percentage of participants who reported decreasing medical visit frequency was 34% at the baseline and 16.5% at follow-up, and those who reported a worsening of chronic diseases was 5.1% and 5.1%, respectively. A worsening of chronic diseases at follow-up was significantly associated with a younger age, a decreased frequency of medical visits, unemployment, a history of smoking, and psychological distress. Conclusions A decreased frequency of medical visits was observed among one-third of the participants with chronic disease in the early stage of the pandemic, and it reduced by half at follow-up. In the early stages of an emerging infectious disease pandemic, decreased regular hospital/clinic visits can lead to a worsening of chronic diseases. Those who had psychological distress, unemployment, and a history of smoking were vulnerable to a worsening chronic disease.

Mental illness and a high-risk, elderly Japanese population: characteristic differences related to gender and residential location.

PURPOSE: Examining the sociodemographic determinants of psychological distress is important in identifying specific subgroups in need of further intervention. However, there are few studies focusing on older populations and on the role of gender or location of residence. To try to clarify characteristics of a population at high risk for mental illness, we examined the sociodemographic determinants of psychological distress in older adults living in three different locations. METHODS: A mail survey was used to collect data on levels of psychological distress and sociodemographic characteristics from a population-based sample of 1894 older adults who lived in Bunkyo (urban setting), Fuchu (suburban setting) and Oyama (rural setting) in Japan (aged 65-74 years, 51.3% men). Psychological distress level was measured based on Kessler's six-item psychological distress scale (K6) and dichotomized into two groups with a cut-off score of 5 (0-4 or 5-24). Multiple logistic regression analyses were used to examine the associations between sociodemographic factors, specifically gender and location of residence, and psychological distress levels. RESULTS: The variables of older age, living in Bunkyo, living in Oyama and living alone were significantly associated with high psychological distress. Although these associations were observed in men, no associations were observed in women. Location-specific analyses showed significant associations between sociodemographic and psychological distress among men living in Oyama, but not among those in Bunkyo or Fuchu. CONCLUSIONS: Sociodemographic factors were significantly correlated with psychological distress, particularly among older men in rural areas. Characteristics of a population at high risk for mental illness may vary based on gender and location of residence. Health promotion initiatives for older adults may be more effective if they take these demographic factors into account.

Estimation of cutoff score for the 7C of vaccination readiness scale.

The 7C of the vaccination readiness scale provides a score to evaluate the willingness and readiness to get vaccinated (vaccination readiness). This cross-sectional study clarifies the cutoff vaccination readiness score to determine whether an individual is willing to be vaccinated. We conducted an online survey of 774 participants. The vaccination readiness scores for the full and short survey versions were calculated. The coronavirus disease 2019 vaccination status was used to determine whether the participant was willing to be vaccinated. Receiver operating characteristic curve analysis was performed using the Youden index. The Youden Index was at its maximum when the cutoff score was 4.02 for the full version (area under the curve [AUC]:0.94) and 4.07 for the short version (AUC:0.90). Vaccination readiness scores greater than 4 on both the full and short version may indicate a willingness to be vaccinated. This cutoff value facilitates the interpretation of the 7C scale results.

The association of subjective vision with objectively measured intensity-specific physical activity and bout-specific sedentary behavior among community-dwelling older adults in Japan.

PURPOSE: Visual impairment is a possible cause of physical frailty. Reduced physical activity (PA) may be involved in the pathway from visual impairment to physical frailty, although the association between vision and objectively measured PA among older adults remains unclear. This study examined the sex-specific association of subjective vision with intensity-specific PA and bout-specific sedentary behavior (SB) among community-dwelling, older Japanese adults. STUDY DESIGN: Cross-sectional study METHODS: This study used data from the Neuron to Environmental Impact across Generations study analyzing older adults (527 participants, aged 65-84 years) living in rural areas of Niigata Prefecture, Japan. Subjective vision was assessed by use of a questionnaire. Intensity-specific PA (light-intensity PA and moderate-to-vigorous PA [MVPA]), bout-specific SB, and daily step count were objectively evaluated by use of an accelerometer. The association of subjective vison with PA and SB, stratified by sex, was analyzed by means of general regression analyses, with adjustment for covariates. RESULTS: The data of 512 participants (men: 46.9%; with poor subjective vision: 22.9%) were analyzed. Poor subjective vision was significantly associated with log MVPA (partial regression coefficient = -0.261, P = .013) and log steps (partial regression coefficient = -0.164; P = .021) among women, whereas a tendency of an association was observed with prolonged SB time among men (partial regression coefficient: 39.1; P = .073). CONCLUSION: Older Japanese women with poor subjective vision performed less MVPA and had fewer step counts than those of participants with good subjective vision, and men with poor subjective vision had longer prolonged SB, which may all accelerate the process to physical frailty.