Publications by authors named "Toru Nabika"

142 Publications

Association between hilliness and walking speed in community-dwelling older Japanese adults: A cross-sectional study.

Arch Gerontol Geriatr 2021 Aug 26;97:104510. Epub 2021 Aug 26.

Center for Community-Based Healthcare Research and Education (CoHRE), Head Office for Research and Academic Information, Shimane University, 223-8 Enya-cho, Izumo-shi, Shimane 693-8501, Japan; Faculty of Human Sciences, Shimane University, 1060 Nishikawatsu-cho, Matsue-shi, Shimane 690-8504, Japan.

Purpose: This cross-sectional study investigated the association between hilliness and walking speed in community-dwelling older adults, and whether it varied according to their car-driving status.

Methods: Data were collected from 590 participants aged 65 and older living in Okinoshima Town, Shimane prefecture, Japan, in 2018. Comfortable walking speed (m/s) was objectively assessed. Hilliness was measured by the mean land slope (degree) within a 500-m or 1000-m network buffer around each participant's home using a geographic information system. A multiple linear regression examined whether the land slope was associated with walking speed, adjusted for sex, age, body mass index, smoking habits, alcohol consumption habits, exercise habits, chronic disease, and living arrangements. A stratified analysis by car-driving status was also conducted.

Results: After adjusting for all confounders, the land slope within the 500-m or 1000-m network buffer was negatively associated with walking speed (B = -0.007, 95% CI [-0.011, -0.002]; B = -0.007, 95% CI [-0.011, -0.003], respectively). The stratified analysis by car-driving status showed that living in a hilly area was negatively associated with walking speed among non-drivers in the 500-m or 1000-m network buffer (B = -0.011, 95% CI [-0.017, -0.004]; B = -0.012, 95% CI [-0.019, -0.006]), though there were no associations among drivers.

Conclusions: A hilly environment is positively associated with slow walking speed in community-dwelling older adults in Japan. Moreover, car-driving status potentially modifies the relationship between living in a hilly environment and slow walking speed.
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http://dx.doi.org/10.1016/j.archger.2021.104510DOI Listing
August 2021

Environmental Factors Affecting Cognitive Function among Community-Dwelling Older Adults: A Longitudinal Study.

Int J Environ Res Public Health 2021 08 12;18(16). Epub 2021 Aug 12.

Department of Medical Education and Research, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo-shi 693-8501, Shimane, Japan.

Although neighborhood environmental factors have been found to be associated with cognitive decline, few longitudinal studies have focused on their effect on older adults living in rural areas. This longitudinal study aimed to investigate the role of neighborhood environmental factors in cognitive decline among rural older adults. The data of 485 older adults aged ≥60 years who were living in Unnan City in Japan and had participated in two surveys conducted between 2014 and 2018 were analyzed. Cognitive function was assessed using the Cognitive Assessment for Dementia, iPad version 2. Elevation, hilliness, residential density, and proximity to a community center were determined using geographic information system. We applied a generalized estimating equation with odds ratios (OR) and 95% confidence intervals (CIs) of cognitive decline in the quartiles of neighborhood environmental factors. A total of 56 (11.6%) participants demonstrated a decrease in cognitive function at follow up. Elevation (adjusted OR 2.58, 95% CI (1.39, 4.77) for Q4 vs. Q1) and hilliness (adjusted OR 1.93, 95% CI (1.03, 3.63) for Q4 vs. Q1) were associated with a higher likelihood of cognitive decline. The second quartiles of residential density showed significantly lower likelihoods of cognitive decline compared with the first quartiles (adjusted OR 0.36, 95% CI (0.19, 0.71) for Q2 vs. Q1). Thus, an elevated hilly environment and residential density predicted cognitive decline among rural older adults.
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http://dx.doi.org/10.3390/ijerph18168528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391693PMC
August 2021

Effect of Multimorbidity on Fragility Fractures in Community-Dwelling Older Adults: Shimane CoHRE Study.

J Clin Med 2021 Jul 22;10(15). Epub 2021 Jul 22.

Department of Neurology, Shimane University Faculty of Medicine, Izumo 693-8501, Japan.

Fragility fractures (FFxs), which are a common musculoskeletal injury in older adults, is associated with an increased frequency of falls. Both FFxs and falls may result from drugs, habits, and co-occurring diseases. We aimed to evaluate the effects of various diseases on the risk of FFx. This retrospective study included 1420 individuals aged ≥60 years. We evaluated the history of clinical FFx and diseases using a detailed questionnaire and a health examination. The risk of comorbidities was assessed using the Age-Adjusted Charlson Comorbidity (AAC) Index. We performed binary logistic regression analysis to determine the risk of FFx and falls after adjusting for covariates. In elderly men, the incidence of FFx positively correlated with rheumatoid arthritis and parent's hip fracture. For elderly women, the incidence of FFx positively correlated with rheumatoid arthritis and antihypertensive drugs but was inversely associated with dyslipidemia and antilipidemic drugs. The FFX risk of older adults with an AAC Index ≥6 was higher than those with an AAC Index of 1-3. In addition, the AAC Index and falls were independently and strongly associated with a higher risk of FFx. Taken together, multimorbidity increases the risk of clinical FFx independent of falls in the community-dwelling elderly population.
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http://dx.doi.org/10.3390/jcm10153225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348412PMC
July 2021

Relationship between Masticatory Function and Bone Mineral Density in Community-Dwelling Elderly: A Cross-Sectional Study.

Healthcare (Basel) 2021 Jul 5;9(7). Epub 2021 Jul 5.

Department of Oral and Maxillofacial Surgery/Oral Care Center, Shimane University Faculty of Medicine, 89-1 Enya Cho, Izumo 693-8501, Shimane, Japan.

The relationship between masticatory function and bone mineral density (BMD) is unclear. This cross-sectional study examined this relationship after adjusting for confounding factors. The subjects were 702 community-dwelling elderly adults (306 men, 396 women) who had been recruited for the Community-Based Healthcare Research and Education study in 2019. Objective masticatory function was assessed using the gummy jelly method. The median for each descriptive statistic was 69.0 years for age, 86.2% for the young adult mean, and 18.0 for masticatory function. Comparisons of the groups with good and poor masticatory function by sex revealed a significant difference in muscle mass and the tooth number for both sexes ( < 0.05). Men showed significant differences in age ( < 0.05) and salivary occult blood findings ( < 0.05). Multivariate analysis using propensity scores showed a significant association between masticatory function and BMD in both sexes (men: odds ratio 163.0, 95% confidence interval 1.36-19,610.55, = 0.04; women: odds ratio 48.65, 95% confidence interval 1.52-1561.15, = 0.03 in women). Masticatory function and BMD in the community-dwelling elderly may be related. However, other factors, including frailty and sarcopenia, may also be involved. Regular oral health care by dentists and dental hygienists may benefit this population.
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http://dx.doi.org/10.3390/healthcare9070845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305999PMC
July 2021

An association analysis between hypertension, dementia, and depression and the phases of pre-sarcopenia to sarcopenia: A cross-sectional analysis.

PLoS One 2021 22;16(7):e0252784. Epub 2021 Jul 22.

Center for Community-Based Healthcare Research and Education (CoHRE), Shimane University, Shimane, Japan.

Sarcopenia is intricately related to aging associated diseases, such as neuropsychiatric disorders, oral status, and chronic diseases. Dementia and depression are interconnected and also related to sarcopenia. The preliminary shift from robust to sarcopenia (i.e., pre-sarcopenia) is an important albeit underdiscussed stage and is the focus of this study. Identifying factors associated with pre-sarcopenia may lead to sarcopenia prevention. To separately examine the effects of dementia and depression on pre-sarcopenia/sarcopenia, we conducted multiple analyses. This cross-sectional study used health checkup data from a rural Japanese island. The participants were aged 60 years and above, and the data included muscle mass, gait speed, handgrip strength, oral status (teeth and denture), chronic diseases (e.g., hypertension), dementia (cognitive assessment for dementia, iPad Version), and depression (self-rating depression scale). A total of 753 older adult participants were divided into the sarcopenia (n = 30), pre-sarcopenia (n = 125), and robust (n = 598) groups. An ordered logit regression analysis indicated that age and depression were positively correlated with sarcopenia, while hypertension was negatively associated with it. A multiple logistic regression analysis between the robust and pre-sarcopenia groups showed significant associations between the same three variables. Depression was associated with pre-sarcopenia, but not dementia. There was also a significant association between hypertension and pre-sarcopenia. Further research is needed to reveal whether the management of these factors can prevent sarcopenia.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252784PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297796PMC
July 2021

Number of teeth and masticatory function are associated with sarcopenia and diabetes mellitus status among community-dwelling older adults: A Shimane CoHRE study.

PLoS One 2021 2;16(6):e0252625. Epub 2021 Jun 2.

Center for Community-Based Healthcare Research and Education (CoHRE), Organization for Research and Academic Information, Shimane University, Izumo City, Shimane, Japan.

Objectives: We aimed to examine the number of teeth and masticatory function as oral health indices and clarify their roles in the pathogenesis of sarcopenia and diabetes mellitus in community-dwelling older adults.

Subjects And Methods: This cross-sectional study was conducted with 635 older adults in Ohnan, Shimane Prefecture, in rural Japan. The number of teeth and masticatory function (measured by the number of gummy jelly pieces collected after chewing) were evaluated by dental hygienists. Sarcopenia status was assessed using handgrip strength, skeletal muscle index, calf circumference, and a possible sarcopenia diagnosis based on the Asian Working Group for Sarcopenia 2019. Diabetes mellitus status was defined as a hemoglobin A1c level ≥6.5% or self-reported diabetes. A multivariable logistic regression model was used to analyze the association between oral health, sarcopenia, and diabetes mellitus after adjusting for confounders.

Results: After adjusting for all confounders, logistic regression analysis showed that the number of remaining teeth was negatively associated with a low level of handgrip strength (odds ratio [OR], 0.961; 95% confidence interval [CI], 0.932-0.992) and possible sarcopenia (OR, 0.949; 95% CI, 0.907-0.992). Higher levels of masticatory function were also negatively associated with a low level of handgrip strength (OR, 0.965; 95% CI, 0.941-0.990) and possible sarcopenia (OR, 0.941; 95% CI, 0.904-0.979). Logistic regression analysis showed that the number of remaining teeth and a higher level of masticatory function were negatively associated with diabetes mellitus (OR, 0.978; 95% CI, 0.957-0.999; OR, 0.976; 95% CI, 0.960-0.992, respectively).

Conclusion: Our findings suggest that improvement in oral health, including the maintenance of masticatory function and remaining teeth, may contribute to the prevention of sarcopenia and diabetes mellitus in older adults.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252625PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172058PMC
June 2021

The trans-ancestral genomic architecture of glycemic traits.

Nat Genet 2021 06 31;53(6):840-860. Epub 2021 May 31.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
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http://dx.doi.org/10.1038/s41588-021-00852-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958PMC
June 2021

Integrative genomic analysis of blood pressure and related phenotypes in rats.

Dis Model Mech 2021 May 19;14(5). Epub 2021 May 19.

Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.

Despite remarkable progress made in human genome-wide association studies, there remains a substantial gap between statistical evidence for genetic associations and functional comprehension of the underlying mechanisms governing these associations. As a means of bridging this gap, we performed genomic analysis of blood pressure (BP) and related phenotypes in spontaneously hypertensive rats (SHR) and their substrain, stroke-prone SHR (SHRSP), both of which are unique genetic models of severe hypertension and cardiovascular complications. By integrating whole-genome sequencing, transcriptome profiling, genome-wide linkage scans (maximum n=1415), fine congenic mapping (maximum n=8704), pharmacological intervention and comparative analysis with transcriptome-wide association study (TWAS) datasets, we searched causal genes and causal pathways for the tested traits. The overall results validated the polygenic architecture of elevated BP compared with a non-hypertensive control strain, Wistar Kyoto rats (WKY); e.g. inter-strain BP differences between SHRSP and WKY could be largely explained by an aggregate of BP changes in seven SHRSP-derived consomic strains. We identified 26 potential target genes, including rat homologs of human TWAS loci, for the tested traits. In this study, we re-discovered 18 genes that had previously been determined to contribute to hypertension or cardiovascular phenotypes. Notably, five of these genes belong to the kallikrein-kinin/renin-angiotensin systems (KKS/RAS), in which the most prominent differential expression between hypertensive and non-hypertensive alleles could be detected in rat Klk1 paralogs. In combination with a pharmacological intervention, we provide in vivo experimental evidence supporting the presence of key disease pathways, such as KKS/RAS, in a rat polygenic hypertension model.
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http://dx.doi.org/10.1242/dmm.048090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188887PMC
May 2021

Assessing the Impact of a Hilly Environment on Depressive Symptoms among Community-Dwelling Older Adults in Japan: A Cross-Sectional Study.

Int J Environ Res Public Health 2021 04 24;18(9). Epub 2021 Apr 24.

Department of Functional Pathology, Faculty of Medicine, Shimane University, Shimane 693-8501, Japan.

Although some neighborhood environmental factors have been found to affect depressive symptoms, few studies have focused on the impact of living in a hilly environment, i.e., land slope, on depressive symptoms among rural older adults. This cross-sectional study aimed to investigate whether a land slope is associated with depressive symptoms among older adults living in rural areas. Data were collected from 935 participants, aged 65 years and older, who lived in Shimane prefecture, Japan. Depressive symptoms were assessed using the Zung Self-Rating Depression Scale (SDS) and defined on the basis of an SDS score ≥ 40. Land slopes within a 400 m network buffer were assessed using geographic information systems. Odds ratios (ORs) with 95% confidence intervals (CIs) of depressive symptoms were estimated using logistic regression. A total of 215 (23.0%) participants reported depressive symptoms. The land slope was positively associated with depressive symptoms (OR = 1.04; 95% CI = 1.01-1.08) after adjusting for all confounders. In a rural setting, living in a hillier environment was associated with depressive symptoms among community-dwelling older adults in Japan.
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http://dx.doi.org/10.3390/ijerph18094520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123156PMC
April 2021

Relationship between Oral Health Status and Bone Mineral Density in Community-Dwelling Elderly Individuals: A Cross-Sectional Study.

Healthcare (Basel) 2021 Apr 7;9(4). Epub 2021 Apr 7.

Oral Care Center, Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Shimane University, Izumo 693-8501, Japan.

The relationship between oral health status and bone mineral density has been poorly elucidated. We conducted a cross-sectional study to examine the relationship between oral health status and bone mineral density with data from healthy community-dwelling elderly individuals in Ohnan-cho, Shimane Japan who were recruited in 2019 for the Shimane Center for Community-Based Health Research and Education (CoHRE) study. The study included 702 participants (306 men and 396 women). The median age, bone mineral density, and number of remaining teeth were 69.0 years, 86.2%, and 26.0, respectively. The two groups (Low teeth group and High teeth group) showed significant differences in age, hemoglobin A1c (HbA1c) level, and masticatory function in men ( < 0.05). In women, age, number of untreated teeth, and masticatory function were significantly different ( < 0.05). The odds ratio of propensity score analysis for the association between the number of remaining teeth and bone mineral density was 27.7 (95% confidence interval: 1.86-414.9, < 0.05). The number of remaining teeth could be associated with bone mineral density in the healthy elderly women, and no significant association was observed in men. Number of remaining teeth and bone mineral density may be interrelated, and oral care by dentists/dental hygienists may play an important role in maintaining bone mineral density in elderly women.
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http://dx.doi.org/10.3390/healthcare9040432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067960PMC
April 2021

Patient satisfaction and loyalty in Japanese primary care: a cross-sectional study.

BMC Health Serv Res 2021 Mar 25;21(1):274. Epub 2021 Mar 25.

Department of Medical Education and Research, Faculty of Medicine, Shimane University, 89-1, Enya-cho, Izumo-shi, Shimane, 693-8501, Japan.

Background: This study aimed to explore associations between various elements of primary care, patient satisfaction, and loyalty.

Methods: This cross-sectional study used a modified version of the Primary Care Assessment Tool (PCAT), which was adapted for Japan. We distributed the PCAT questionnaire to patients aged 20 years or older at five rural primary care centres in Japan. We confirmed the validity and reliability of the measure for our study. Next, we examined which elements of primary care were related to patient satisfaction and loyalty using Spearman's correlation and structural equation modelling.

Results: Of 220 eligible patients, 206 participated in this study. We developed nine component scales: first contact (regular access), first contact (urgent access), longitudinality, coordination, comprehensiveness (variety of care), comprehensiveness (risk prevention), comprehensiveness (health promotion), family-centeredness, and community orientation. Longitudinality and first contact (urgent access) were related with patient satisfaction. Longitudinality, first contact (regular access), and family-centeredness were related to patient loyalty. In the structural equation modelling analysis, two variables were significantly related to loyalty, namely a combined variable including longitudinality and first contact (regular access), along with family-centeredness.

Conclusions: While a patient satisfaction model could not be distilled from the data, longitudinality, first contact (urgent access), and family-centeredness were identified as important elements for the cultivation of patient loyalty. This implies that primary care providers need to develop a deep understanding of patients' contexts and concerns and pay attention to their level of access to cultivate greater patient loyalty.
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http://dx.doi.org/10.1186/s12913-021-06276-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992825PMC
March 2021

Neighborhood Environmental Factors and Physical Activity Status among Rural Older Adults in Japan.

Int J Environ Res Public Health 2021 02 4;18(4). Epub 2021 Feb 4.

Center for Community-Based Healthcare Research and Education (CoHRE), Organization for Research and Academic Information, Shimane University, 223-8 Enya-cho, Izumo-shi, Shimane 693-8501, Japan.

(1) Background: Although several neighborhood environmental factors have been identified to be associated with older adults' physical activity, little research has been done in rural areas where the population is aging. This study aimed to investigate neighborhood environmental factors and the longitudinal change of physical activity status among rural older adults in Japan. (2) Methods: The study included 2211 older adults, aged over 60 years, residing in three municipalities in Shimane prefecture and participating at least twice in annual health checkups between 2010 and 2019. Physical activity was identified based on self-report. Hilliness, bus stop density, intersection density, residential density, and distance to a community center were calculated for each subject. Hazard ratios for the incidence of physical inactivity were estimated using Cox proportional hazards models. (3) Results: We found that 994 (45%) of the study subjects became physically inactive during the follow-up. Those living far from a community center had a lower risk of becoming physically inactive compared to those living close to a community center. When the analysis was stratified by residential municipality, this association remained in Ohnan town. Those living in hilly areas had a higher risk of becoming physically inactive in Okinoshima town. (4) Conclusions: The impact of neighborhood environmental factors on older adults' physical activity status might differ by region possibly due to different terrain and local lifestyles.
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http://dx.doi.org/10.3390/ijerph18041450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913898PMC
February 2021

Inconvenience of Living Place Affects Individual HbA1c Level in a Rural Area in Japan: Shimane CoHRE Study.

Int J Environ Res Public Health 2021 01 28;18(3). Epub 2021 Jan 28.

Department of Functional Pathology, Faculty of Medicine, Shimane University, Izumo, Shimane 693-8501, Japan.

Background: It has been shown that the socio-geographical environment of residential areas, such as altitude, affects the health status and health-maintenance behavior of residents. Here, we examined a hypothesis that altitude of residence would influence glycemic control in a general elderly population living in a rural area.

Methods: A thousand and sixteen participants living in a mountainous region in Japan were recruited at health examinations. Hemoglobin A1c (HbA1c) was measured in serum as a parameter of glycemic control. The altitude of residence, distance to grocery stores and to medical facilities were estimated using a geographic information system.

Results: Linear regression analysis confirmed a significant effect of the altitude on log HbA1c even after adjustment of other demographic and biochemical factors. When the distance to grocery stores or medical facilities were used instead of the altitude in a linear regression analysis, distance to secondary medical facilities alone showed a significant effect on HbA1c.

Conclusions: We found a positive correlation between HbA1c level and residential altitude in a rural area of Japan. The altitude seemed to be a parameter substituting the inconvenicence of residential areas. Socio-geographical factors of living place, such as inconvenience, may influence glycemic control of the residents.
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http://dx.doi.org/10.3390/ijerph18031147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908499PMC
January 2021

Social participation and physical prefrailty in older Japanese adults: The Shimane CoHRE study.

PLoS One 2020 16;15(12):e0243548. Epub 2020 Dec 16.

Center for Community-Based Healthcare Research and Education (CoHRE), Organization for Research and Academic Information, Shimane University, Izumo City, Shimane, Japan.

As older adults in an early stage (prefrailty) of frailty may return to a healthy state, it is necessary to examine the prevention of prefrailty. In this context, the number and types of social participation activities associated with physical prefrailty in community-dwelling older adults have remained relatively unexplored. This cross-sectional study investigates this issue by analyzing 616 participants living in Okinoshima, Shimane, a rural area of Japan, in 2019. Frailty was assessed using the 5-item frailty phenotype (unintentional weight loss, self-reported exhaustion, weakness, slow walking speed, and low physical activity). Data on social participation were obtained using a questionnaire based on participants' level of involvement with volunteer groups, sports clubs/groups, neighborhood associations, religious organizations/groups, and community elderly salons; their answers were categorized as "yes" if they answered "several times per year or more" and "no" if they answered "never." Binominal logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of prefrailty by the number or types of social participation activities, adjusted for gender, age, body mass index, smoking, medication-taking, educational attainment, working status, and living arrangement. Of the 616 participants, 273 (44.3%) and 28 (4.5%) had prefrailty and frailty, respectively. The analysis showed that the number of social participation activities was significantly associated with lower odds of prefrailty (OR = 0.83; 95% CI, 0.74-0.94). Regarding the types of social participation, sports clubs/groups were associated with lower odds of prefrailty (OR = 0.47; 95% CI, 0.31-0.73). Participation in neighborhood associations was associated with prefrailty/frailty (OR = 0.57; 95% CI, 0.37-0.86). These results suggest that increasing the number of social participation activities or involvement in sports clubs/groups and neighborhood associations may be important to prevent physical prefrailty in the older population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243548PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7743931PMC
February 2021

Neighborhood environment and muscle mass and function among rural older adults: a 3-year longitudinal study.

Int J Health Geogr 2020 11 25;19(1):51. Epub 2020 Nov 25.

Center for Community-Based Healthcare Research and Education (CoHRE), Organization for Research and Academic Information, Shimane University, 223-8 Enya-cho, Izumo-shi, Shimane, 693-8501, Japan.

Background: Sarcopenia, resulting from loss of muscle mass and function, is highly prevalent in the ageing societies and is associated with risk of falls, frailty, loss of independence, and mortality. It is important to identify environmental risk factors, so that evidence-based interventions to prevent sarcopenia can be implemented at the population level. This study aimed to examine the potential effect of several objectively measured neighborhood environmental factors on longitudinal change of muscle mass and function among older adults living in rural Japanese towns where the population is ageing.

Methods: This study was based on data from the Shimane CoHRE Study conducted by the Center for Community-based Healthcare Research and Education (CoHRE) at Shimane University in 3 rural towns in the Shimane Prefecture, Japan. Subjects older than 60 years, who participated in an annual health examination in 2016 and any follow-up years until 2019, i.e., 4 possible time points in total, were included (n = 2526). The skeletal muscle mass index (SMI) and grip strength were assessed objectively for each year as a measure of muscle mass and function, respectively. Neighborhood environmental factors, i.e., hilliness, bus stop density, intersection density, residential density, and distance to a community center were measured by geographic information systems (GIS). Linear mixed models were applied to examine the potential effect of each neighborhood environmental factor on the change of SMI and grip strength over time.

Results: Males living far from community centers had a less pronounced decline in SMI compared to those living close to community centers. Females living in areas with higher residential density had a less pronounced decline in grip strength compared to those living in areas with lower residential density.

Conclusions: Neighborhood environmental factors had limited effects on change of SMI and grip strength among rural older adults within the 3 years follow up. Further long-term follow up studies are necessary by also taking into account other modifiable neighborhood environmental factors.
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http://dx.doi.org/10.1186/s12942-020-00247-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690178PMC
November 2020

Pathophysiological significance of mutation in sympathetic response to stress and cardiovascular phenotypes in SHRSP/Izm: In vivo evaluation by creation of a novel gene knock-in rat using CRISPR/Cas9.

Clin Exp Hypertens 2021 Jan 23;43(1):34-41. Epub 2020 Jul 23.

Department of Functional Pathology, Faculty of Medicine, Shimane University , Izumo, Japan.

Genetic approach using rat congenic lines between SHRSP/Izm and WKY/Izm identified stromal interaction molecule 1 (), an essential component of store-operated Ca entry (SOCE), as a promising candidate gene responsible for the exaggerated sympathetic response to stress in SHRSP. Since SHRSP has a nonsense mutation in resulting in the expression of a truncated form of STIM1 that caused reduction of SOCE activity in primary cultured cerebral astrocytes, we created SHRSP/Izm knocked-in with the wild-type (KI SHRSP) by the CRISPR/Cas9 method to investigate whether the functional recovery of STIM1 would mitigate sympatho-excitation to stress in SHRSP. No potential off-target nucleotide substitutions/deletions/insertions were found in KI SHRSP. Western blotting and fluorescent Ca imaging of astrocytes confirmed wild-type STIM1 expression and restored SOCE activity in astrocytes from KI SHRSP, respectively. Blood pressure (BP) measured by the tail-cuff method at 12, 16, and 20 weeks of age did not significantly differ between SHRSP and KI SHRSP, while the heart rate of KI SHRSP at 16 and 20 weeks of age was significantly lower than that of age-matched SHRSP. Unexpectedly, the sympathetic response to stress (evaluated with urinary excretion of norepinephrine under cold stress and BP elevation under cold/restraint stress) did not significantly differ between SHRSP and KI SHRSP. The present results indicated that the functional deficit of STIM1 was not a genetic determinant of the exaggerated sympathetic response to stress in SHRSP and that it would be necessary to explore other candidates within the congenic fragment on chromosome 1.
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http://dx.doi.org/10.1080/10641963.2020.1797085DOI Listing
January 2021

Defective Function of the Blood-Brain Barrier in a Stroke-Prone Spontaneously Hypertensive Rat: Evaluation in an In Vitro Cell Culture Model.

Cell Mol Neurobiol 2020 Jul 9. Epub 2020 Jul 9.

Department of Functional Pathology, Shimane University Faculty of Medicine, Izumo, Japan.

The blood-brain barrier (BBB) comprises three cell types: brain capillary endothelial cells (BECs), astrocytes, and pericytes. Abnormal interaction among these cells may induce BBB dysfunction and lead to cerebrovascular diseases. The stroke-prone spontaneously hypertensive rat (SHRSP) harbors a defective BBB, so we designed the present study to examine the role of these three cell types in a functional disorder of the BBB in SHRSP in order to elucidate the role of these cells in the BBB more generally. To this end, we employed a unique in vitro model of BBB, in which various combinations of the cells could be tested. The three types of cells were prepared from both SHRSPs and Wistar Kyoto rats (WKYs). They were then co-cultured in various combinations to construct in vitro BBB models. The barrier function of the models was estimated by measuring transendothelial electrical resistance and the permeability of the endothelial monolayer to sodium fluorescein. The in vitro models revealed that (1) BECs from SHRSPs had an inherent lower barrier function, (2) astrocytes of SHRSPs had an impaired ability to induce barrier function in BECs, although (3) both pericytes and astrocytes of SHRSPs and WKYs could potentiate the barrier function of BECs under co-culture conditions. Furthermore, we found that claudin-5 expression was consistently lower in models that used BECs and/or SHRSP astrocytes. These results suggested that defective interaction among BBB cells-especially BECs and astrocytes-was responsible for a functional disorder of the BBB in SHRSPs.
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http://dx.doi.org/10.1007/s10571-020-00917-zDOI Listing
July 2020

Fast food outlets, physical activity facilities, and obesity among adults: a nationwide longitudinal study from Sweden.

Int J Obes (Lond) 2020 08 19;44(8):1703-1711. Epub 2020 May 19.

Center for Primary Health Care Research, Lund University, Malmö, Sweden.

Background: While neighborhood deprivation is a well-known predictor of obesity, the mechanisms behind this association are unclear and these are important to clarify before designing interventions focusing on modifiable neighborhood environmental factors in order to reduce obesity risk.

Objectives: This study examined the longitudinal association between availability of fast-food outlets and physical activity facilities and the risk of obesity among adults.

Methods: This study used multiple national register data from Sweden. During the 11-year follow-up period between 2005 and 2015, data from 1,167,449 men and 542,606 women, aged 20-55 years, were accessible for inclusion in this analysis. Incidence of obesity was identified based on a diagnosis of obesity during the follow-up period derived from clinical register data. Neighborhood availability of fast-food outlets and physical activity facilities were assessed in 2005 and Cox regression was used in the statistical analysis. Individual socio-demographic factors and neighborhood deprivation were used as covariates.

Results: There were no meaningful associations between neighborhood fast-food outlets or physical activity facilities and obesity in men or women. Neighborhood deprivation was, however, consistently and strongly associated with incidence of obesity in both men and women.

Conclusions: Availability of fast-food outlets and lack of physical activity facilities appear unlikely to cause obesity in Swedish adults. Other potentially modifiable environmental factors within specific social and cultural settings that may influence obesity risk should be examined in future studies.
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http://dx.doi.org/10.1038/s41366-020-0588-5DOI Listing
August 2020

Hilly environment and physical activity among community-dwelling older adults in Japan: a cross-sectional study.

BMJ Open 2020 03 26;10(3):e033338. Epub 2020 Mar 26.

Center for Community-Based Healthcare Research and Education (CoHRE), Organization for Research and Academic Information, Shimane University, Izumo, Shimane, Japan.

Objectives: We investigated whether a moderate-to-vigorous physical activity (MVPA) level and walking time were associated with a hilly environment in rural Japanese older adults.

Design: Cross-sectional study.

Setting: Unnan city, Ohnan and Okinoshima towns in Shimane, Japan.

Participants: Data were collected from 1115 adults from the Shimane CoHRE study, who were aged 60 years and older and living in rural Japan in 2012.

Measures: We measured the total time spent on MVPA and walking using a Japanese short version of the International Physical Activity Questionnaire. The land slope in 400 or 800 m network buffers was assessed using the geographic information system. A multivariable Poisson regression model examined the prevalence ratios (PR) and 95% CIs of walking time or MVPA levels meeting the WHO guideline (150 min/week) in the land slope categories (low, middle and high), adjusted for confounders.

Results: Engaging in the recommended level of MVPA was significantly associated with middle land slope (PR=1.07; p=0.03) and high land slope (PR=1.06; p=0.07) compared with low land slope in the 400 m network buffer, as well as with middle land slope (PR=1.02; p=0.48) and high land slope (PR=1.04; p=0.25) compared with the low land slope in the 800 m network buffer. Walking time was significantly associated with middle land slope (PR=1.13; p=0.04) and high land slope (PR=1.17; p=0.01) compared with low land slope in the 400 m network buffer, and with middle land slope (PR=1.09; p=0.16) and high land slope (PR=1.17; p<0.01) compared with low land slope in the 800 m network buffer. The sensitivity analysis found only a positive association between walking time and land slope in the 400 and 800 m network buffers.

Conclusions: This study showed that a hilly environment was positively associated with walking time among older adults living in rural Japan.
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http://dx.doi.org/10.1136/bmjopen-2019-033338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170569PMC
March 2020

Association between cystatin C gene polymorphism and the prevalence of white matter lesion in elderly healthy subjects.

Sci Rep 2020 03 13;10(1):4688. Epub 2020 Mar 13.

Department of Neurology, Shimane University Faculty of Medicine, Izumo, Japan.

Cystatin C (CST3) is a cysteine protease inhibitor abundant in the central nervous system, and demonstrated to have roles in several pathophysiological processes including vascular remodeling and inflammation. Previously, we showed a relation of CST3 gene polymorphisms with deep and subcortical white matter hyperintensity (DSWMH) in a small case-control study. In this study, we aimed to investigate the relation in a larger cross-sectional study. Participants of a brain health examination program were recruited (n = 1795) in the study, who underwent routine blood tests and cognitive function tests. Cerebral white matter changes were analyzed by MRI. Additionally, 7 single nucleotide polymorphisms (SNPs) (-82G/C, -78T/G, -5G/A, +4A/C, +87C/T, +148G/A and +213G/A) in the promoter and coding regions of CST3 gene were examined. Among them, carriers of the minor allele haplotype -82C/+4C/+148A were significantly associated with decreased CST3 concentration in the plasma. Unadjusted analysis did not show significant relation between carriers of the minor allele haplotype and periventricular hyperintensity (PVH), but DSWMH was marginally (p < 0.054) increased in this group. After adjusting the effects of other variables like age and kidney function, logistic regression analysis revealed that carriers of the minor allele haplotype were at a significantly increased risk of developing both PVH and DSWMH. Thus, our results suggest that carriers of the minor allele haplotype -82C/+4C/+148A of CST3 gene could be at an increased risk to develop cerebral white matter disturbance.
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http://dx.doi.org/10.1038/s41598-020-61383-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069982PMC
March 2020

Prevalence of lifestyle-related chronic diseases among agricultural and non-agricultural workers in ruralareas of Japan: the Shimane CoHRE study.

J Rural Med 2020 Jan 23;15(1):1-7. Epub 2020 Jan 23.

The Center for Community-based Healthcare Research and Education (CoHRE), Shimane University, Japan.

Engaging in agriculture greatly affects workers' lifestyles, particularly related to physical activity. This study aimed to clarify the prevalence of lifestyle-related chronic diseases among workers engaging and not engaging in agriculture in rural areas of Japan. A total of 4,666 consecutive participants aged ≥40 years (1,929 men and 2,737 women) were recruited during health examinations conducted from 2006 to 2014. For analysis, the participants were divided by sex and age into those engaging in agriculture and those not engaging in agriculture. Engaging in agriculture may be contributing with a low prevalence of dyslipidemia, a constitutive factor of metabolic syndrome, in both sexes between the ages of 40 and 64 years. In the elderly aged ≥65 years, engaging in agriculture may influence the low prevalence of hypertension in men. Hypertension, a strong risk factor for stroke and cardiovascular disease, is very frequent among the Japanese elderly and, therefore, engaging in agriculture may have a significant impact on its prevention and control. In rural areas of Japan, engaging in agriculture may contribute to the control of lipid metabolism in middle-aged individuals and blood pressure in the elderly.
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http://dx.doi.org/10.2185/jrm.2019-008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983452PMC
January 2020

Prevalence and Correlates of Physical Activity Among Children and Adolescents: A Cross-Sectional Population-Based Study of a Rural City in Japan.

J Epidemiol 2020 Sep 10;30(9):404-411. Epub 2019 Aug 10.

College of Health and Welfare, J. F. Oberlin University.

Background: Although moderate-to-vigorous physical activity (MVPA) has multiple health benefits, current participation in recommended MVPA level and its determinants among Japanese children and adolescents remain unclear. Therefore, this cross-sectional study investigated the prevalence of meeting recommended MVPA level and its correlates among Japanese children and adolescents.

Methods: Using the Japanese version of the World Health Organization (WHO) Health Behaviour in School-aged Children survey questionnaire, we confirmed the prevalence of meeting recommended MVPA level in all primary schools (PS) and junior high schools (JHS) in Unnan City, Japan. We evaluated its association with school grade, gender, body weight status, screen time, consumption of breakfast, physical activity (PA) preference, and population density using Poisson regression.

Results: We found that 20.1% of the 1,794 students (9-15 years old) met the WHO recommendation. Meeting recommended MVPA level was significantly associated with being in the sixth grade of PS (prevalence ratio [PR] 0.57; 95% confidence interval [CI], 0.39-0.84) and first (PR 1.52; 95% CI, 1.16-1.99), second (PR 1.45; 95% CI, 1.10-1.90), and third grade of JHS (PR 0.40; 95% CI, 0.26-0.62) (vs fourth grade of PS); being a boy (PR 1.33; 95% CI, 1.12-1.59) (vs girl); liking PA (PR 3.72; 95% CI, 2.22-6.22) (vs dislike); and belonging to a medium-population-density (PR 0.73; 95% CI, 0.61-0.88) or low-population-density area (PR 0.67; 95% CI, 0.48-0.94) (vs high-population-density area).

Conclusions: About 20% of Japanese children and adolescents engaged in the recommended MVPA level. MVPA was associated with grade, gender, preference for PA, and population density.
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http://dx.doi.org/10.2188/jea.JE20190047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429150PMC
September 2020

J-curve association between alcohol intake and varicose veins in Japan: The Shimane CoHRE Study.

J Dermatol 2019 Oct 29;46(10):902-906. Epub 2019 Jul 29.

Department of Dermatology, Shimane University Faculty of Medicine, Izumo, Japan.

The effect of alcohol intake on varicose veins (VV) has not been determined by its consumption level. The aim of this study was to investigate the association between alcohol intake and VV in an elderly general population. Using a cross-sectional approach, the Shimane CoHRE Study data, comprising a total of 1060 participants, were analyzed. By multivariate regression analysis adjusted with basic characteristics, past work history, lifestyle-related factors and medical history, compared with non-drinkers, mild drinkers (<20.0 g/day) showed a significantly lower adjusted odds ratio (aOR) of VV (aOR = 0.64, P = 0.036). In a similar way, regular drinkers (1-5 days/week) showed a significantly lower aOR of VV when compared with occasional drinkers (aOR = 0.57, P = 0.032). VV and alcohol intake showed J-curve relationships. In a stratified analysis by alcohol consumption levels, the association of smoking and VV were also observed in moderate to heavy drinkers and habitual drinkers. These findings can provide better understanding of pathophysiological mechanism and be used for evidence-based patient education.
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http://dx.doi.org/10.1111/1346-8138.15022DOI Listing
October 2019

Relationship between Individual Social Capital and Cognitive Function among Older Adults by Gender: A Cross-Sectional Study.

Int J Environ Res Public Health 2019 06 17;16(12). Epub 2019 Jun 17.

Center for Community-Based Healthcare Research and Education (CoHRE), Organization for Research and Academic Information, Shimane University, 223-8 Enya-cho, Izumo-shi, Shimane 693-8501, Japan.

As it is not easy to modify lifestyle, it is important to examine the effect of social capital (SC), which does not require behavior modifications, on dementia prevention. This study aimed to clarify gender differences in the relationship between cognitive function and individual SC among people living in a rural area in Japan. We used the Shimane Center for Community-based Healthcare Research and Education (CoHRE) study data from 2011 to conduct a cross-sectional analysis. The analysis included 491 participants, aged 40 years or older, who had undergone medical examinations in two rural towns in Japan. Both cognitive SC and structural SC were measured. Multivariate logistic regression analysis was conducted to estimate the odds ratios (OR) and 95% confidence interval (CI) for cognitive function levels as binary outcomes. We found a significant association between cognitive function and individual cognitive SC in men (OR: 3.11, 95% CI: 1.43-6.78), and found that cognitive function was associated with structural SC in women (OR: 1.89, 95% CI: 1.08-3.31). This study showed that the relationship between cognitive function and individual SC differed by gender. These results suggest that it is important to approach dementia prevention differently in men and women.
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http://dx.doi.org/10.3390/ijerph16122142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616497PMC
June 2019

Hilly neighborhoods are associated with increased risk of weight gain among older adults in rural Japan: a 3-years follow-up study.

Int J Health Geogr 2019 05 10;18(1):10. Epub 2019 May 10.

Department of Functional Pathology, Faculty of Medicine, Shimane University, 89-1, Enya-cho, Izumo-shi, Shimane, 693-8501, Japan.

Background: Neighborhood environments have been regularly associated with the weight status. Although the evidence is mostly limited to adults residing in western urban settings, the weight status of older adults living in rural areas is also assumed to be significantly affected by their neighborhood environments. This study aimed to identify environmental attributes specific to rural areas that could affect the risk of longitudinal weight gain among older adults (≥ 65 years) in Japan.

Methods: We examined five environmental attributes, i.e., land slope, public transportation accessibility, residential density, intersection density, and the availability of parks and recreational centers, measured by the geographic information system. Our analysis was based on 714 subjects participated in Shimane Community-based Healthcare Research and Education study in 2012 and 2015. Multinomial logistic regression model was conducted to examine the association between each neighborhood environmental attribute and weight change status (gain, loss and unchanged).

Results: We observed a significant increase in the risk of weight gain as the steepness of the neighborhood land slope increased. There was no significant association between other environmental attributes and risk of weight gain as well as weight loss among older adults.

Conclusion: Living in hilly neighborhoods was associated with increased risk of weight gain among rural Japanese older adults. Future research should consider region-specific environmental attributes when investigating their effect on older adults' weight status.
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http://dx.doi.org/10.1186/s12942-019-0174-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509780PMC
May 2019

Height loss but not body composition is related to low back pain in community-dwelling elderlies: Shimane CoHRE study.

BMC Musculoskelet Disord 2019 May 10;20(1):207. Epub 2019 May 10.

Center for Community-Based Healthcare Research and Education (CoHRE), Shimane University, Matsue-city, Shimane, Japan.

Background: Low back pain (LBP) is a common complaint in the elderly Japanese population. Although previous studies showed that height loss was associated with LBP, it remains unclear whether LBP is associated with body composition. The objective of the present study was to investigate whether body composition and physical characteristics, including height loss, were associated with LBP.

Methods: The present study is retrospectively registered, and the participants were 2212 community-dwelling Japanese people aged over 60 years who participated in the Shimane CoHRE study in 2016. We investigated the presence of LBP, body composition parameters (muscle, fat, body weight, and bone mass), physical characteristics (body height and height loss), chronic diseases, history of fall, smoking, and drinking habits. We examined the relationships of body composition parameters and physical characteristics with point prevalence of LBP using multivariate logistic regression.

Results: The point prevalence of LBP was 43.2% in women and 39.5% in men. Logistic regression models showed that body height and body composition were not significantly associated with LBP; however, height loss was associated significantly with LBP in women and men (OR: 1.14, 95% CI: 1.08-1.20 and OR: 1.13, 95% CI: 1.06-1.21, respectively). Hypertension (OR: 1.32, 9 5% CI: 1.04-1.69) and chronic heart disease (OR: 1.57, 95% CI: 1.01-2.43) in women and history of fall (OR: 1.70, 95% CI: 1.13-2.56) and cerebrovascular disease (OR: 1.88, 95% CI: 1.05-3.34) in men were significantly associated with LBP. However, body composition was not associated with LBP in either gender.

Conclusions: The present study demonstrated that height loss, but not body composition, was related to LBP in community-dwelling elderly people. To elucidate the cause of LBP, it is important to consider the relationship with height loss.
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http://dx.doi.org/10.1186/s12891-019-2580-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511157PMC
May 2019

Dual inhibition of NADPH oxidases and xanthine oxidase potently prevents salt-induced stroke in stroke-prone spontaneously hypertensive rats.

Hypertens Res 2019 07 8;42(7):981-989. Epub 2019 Mar 8.

Department of Functional Pathology, Shimane University School of Medicine, Izumo, Japan.

Oxidative stress has been implicated in the pathophysiology of cerebral stroke. As NADPH oxidases (NOXs) play major roles in the regulation of oxidative stress, we hypothesized that reduction of NOX activity by depletion of p22phox, an essential subunit of NOX complexes, would prevent cerebral stroke. To investigate this, we used the stroke-prone spontaneously hypertensive rat (SHRSP) and the p22phox-deleted congenic SHRSP. Although p22phox depletion reduced blood pressure under salt loading, it did not ameliorate oxidative stress or reduce the incidence of salt-induced stroke in SHRSPs. Additional pharmacological reduction of oxidative stress using antioxidant reagents with different mechanisms of action was necessary to prevent stroke, indicating that NOX was not the major target in salt-induced stroke in SHRSPs. On the other hand, oxidative stress measured based on urinary isoprostane levels showed significant correlations with blood pressure, stroke latency and urinary protein excretion under salt loading, suggesting an important role of oxidative stress per se in hypertension and hypertensive organ damage. Overall, our results imply that oxidative stress from multiple sources influences stroke susceptibility and other hypertensive disorders in salt-loaded SHRSPs.
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http://dx.doi.org/10.1038/s41440-019-0246-2DOI Listing
July 2019

Effect of geographic accessibility to primary care on treatment status of hypertension.

PLoS One 2019 4;14(3):e0213098. Epub 2019 Mar 4.

Center for Community-based Healthcare Research and Education (CoHRE), Organization for Research and Academic Information, Shimane University, Izumo City, Shimane, Japan.

Although primary care access is known to be an important factor when seeking care, its effect on individual health risk has not been evaluated by an appropriate spatial measure. This study examined whether geographic accessibility to primary care assessed by a sophisticated form of spatial measure is associated with a risk of hypertension and its treatment status among Japanese people in rural areas, where primary care is not yet established as specialization. We used an enhanced two-step floating catchment area method to calculate the neighborhood residential unit-level primary and secondary care accessibility for 52,029 subjects who participated in the 2015 annual health checkup held at 15 cities in Shimane Prefecture. Their hypertension level and treatment status were examined cross-sectionally with their neighborhood primary care and secondary care accessibility (computed with two separate distance-decay weight: slow and quick) by multivariable logistic regression controlling for demographics and neighborhood income level. The findings showed that greater geographic accessibility to primary care was associated with a decreased risk of hypertension in both slow and quick distance-decay weight, odds ratio (OR) = 0.989 (95% Confidence Interval (CI) = 0.984, 0.994), OR = 0.989 (95%CI = 0.984, 0.993), respectively. On the other hand, better secondary care accessibility was associated with an increased risk of hypertension and untreated hypertension; however, the effect of secondary care was mitigated by the effect of primary care accessibility in both slow and quick distance-decay model, hypertension: OR = 0.974 (95% CI = 0.957, 0.991), OR = 0.981 (95%CI = 0.970, 0.991), untreated hypertension: OR = 0.970 (95%CI = 0.944, 0.996), OR = 0.975 (95%CI = 0.959, 0.991), respectively. In addition, the results revealed that young and fit people were at a higher risk of untreated hypertension, which is a unique finding in the context of the Japanese healthcare system. Our findings indicate the importance of primary care even in Japan, where it is not yet established, and also emphasize the need for a culturally specific perspective in health equity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213098PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398859PMC
December 2019

Evaluation of Pathological Association between Stroke-Related QTL and Salt-Induced Renal Injury in Stroke-Prone Spontaneously Hypertensive Rat.

Biomed Res Int 2019 16;2019:5049746. Epub 2019 Jan 16.

Department of Functional Pathology, Shimane University Faculty of Medicine, Izumo, Japan.

The stroke-prone spontaneously hypertensive rat (SHRSP) suffers from severe hypertension and hypertensive organ damage such as cerebral stroke and kidney injury under salt-loading. By a quantitative trait locus (QTL) analysis between SHRSP and SHR (the stroke-resistant parental strain of SHRSP), two major QTLs for stroke susceptibility were identified on chromosomes 1 and 18 of SHRSP, which were confirmed in congenic strains constructed between SHRSP and SHR. As the progression of renal dysfunction was suggested to be one of the key factors inducing stroke in SHRSP, we examined effects of the stroke-related QTLs on kidney injury using two congenic strains harboring either of SHRSP-derived fragments of chromosomes 1 and 18 in the SHR genome. The congenic strains were challenged with 1% NaCl solution for 4 weeks; measurement of systolic blood pressure and urinary isoprostane level (a marker for oxidative stress) and evaluation of renal injury by quantification of genetic marker expression and histological examination were performed. We found that the congenic rats with SHRSP-derived fragment of chromosome 18 showed more severe renal damage with higher expression of (a genetic marker for renal fibrosis) and higher urinary isoprostane level. In contrast, the fragment of chromosome 1 from SHRSP did not give such effects on SHR. Blood pressure was not greater in either of the congenic strains when compared with SHR. We concluded that the QTL region on chromosome 18 might deteriorate salt-induced renal injury in SHR through a blood pressure-independent mechanism.
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http://dx.doi.org/10.1155/2019/5049746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354164PMC
May 2019

Chronobiological characteristics of locomotor activity in congenic rats (SHRSPwch1.0) and their effects on arterial pressure.

Clin Exp Hypertens 2020 6;42(1):43-51. Epub 2019 Feb 6.

Department of Functional Pathology, Shimane University School of Medicine, Izumo, Japan.

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http://dx.doi.org/10.1080/10641963.2019.1571598DOI Listing
February 2019
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