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BACKGROUND: Uric acid is both a pro-oxidant and an antioxidant. This study examined whether serum uric acid (SUA) is associated with all-cause mortality and cardiovascular biomarkers in members of the general population who had varying levels of handgrip strength (HGS). METHODS: The analysis is based on 1736 participants, of whom 785 were male (69 ± 11 years old) and 951 were female (69 ± 9 years old). We obtained adjusted relative risk estimates for all-cause mortality from the Japanese Basic Resident Registry and used a Cox proportional hazards model (adjusted for possible confounders) to determine the hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: The results indicated a significant interaction between the effects of SUA levels and HGS on all-cause mortality risk. Among participants with low HGS (<30.0 kg in males, <20.0 kg in females), low SUA levels (<3.5 mg/dL in males, <3.0 mg/dL in females; HR: 2.40; 95% CI: 1.07-5.40) and high SUA levels (≥8.0 mg/dL in males, ≥7.0 mg/dL in females; HR: 3.05; 95% CI: 1.41-6.59) were associated with a significantly higher HR for all-cause mortality than medium SUA levels (3.5-7.9 mg/dL in males, 3.0-6.9 mg/dL in females). Among participants with high HGS (≥30.0 kg in males; ≥20.0 kg in females), there was no difference between the HR for all-cause mortality between the three SUA-category groups. CONCLUSIONS: The association between SUA and the risk of all-cause mortality was U-shaped for this population of community-dwelling adults. This was primarily true for those with low HGS.

DOI： 10.1016/j.metop.2022.100227

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Language：Japanese   Publisher：(一社)日本内科学会  

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Anthropometric evaluation is a simple yet essential indicator of muscle and fat mass when studying life prognosis in aging. This study aimed to investigate the contributions of anthropometric measurements, independent of body mass index, to measures of all-cause mortality. We examined data for 1,704 participants from the 2014 Nomura Cohort Study who attended follow-ups for the subsequent eight years (follow-up rate: 93.0%). Of these, 765 were male (aged 69 ± 11 years) and 939 were female (aged 69 ± 9 years). The Japanese Basic Resident Registry provided data on adjusted relative hazards for all-cause mortality. The data were subjected to a Cox regression analysis, wherein the time variable was age and the risk factors were gender, age, anthropometric index, smoking habits, drinking habits, exercise habits, cardiovascular history, hypertension, lipid levels, diabetes, renal function, and serum uric acid. Of the total number of participants, 158 (9.3%) were confirmed to have died, and of these, 92 were male (12.0% of all male participants) and 66 were female (7.0% of all female participants). The multivariable Cox regression analysis revealed that a smaller thigh-hip ratio predicted eight-year all-cause mortality in male participants, but only baseline body mass index was associated with all-cause mortality in female participants. Thigh-hip ratio is a useful predictor of death in Japanese community-dwelling men.

DOI： 10.1371/journal.pone.0292287

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There is limited research on the association between longitudinal variability in serum uric acid (SUA) and all-cause mortality in the general population, although recent studies have suggested that changes in SUA are associated with all-cause mortality in adults. This study aims to examine the association between percentage change in SUA (%dSUA = 100 × (cohort 2 SUA - cohort 1 SUA)/(time × cohort 1 SUA) and all-cause mortality. This study is based on 1,301 participants, of whom 543 were male (63 ± 11 years) and 758 were female (63 ± 9 years). We obtained adjusted relative risk estimates for all-cause mortality and used a Cox proportional hazards model, adjusted for possible confounders, to determine the hazard ratio (HR) and 95% confidence interval (CI) of %dSUA. Of all the participants, 79 (6.1%) were deceased, and of these, 45 were male (8.3%) and 34 were female (4.5%). The multivariable-adjusted HRs (95% CI) for all-cause mortality for the first, second to fourth (reference), and fifth %dSUA quintiles were 3.79 (1.67-8.48), 1.00, and 0.87 (0.29-2.61) for male participants and 4.00 (1.43-11.2), 1.00, and 1.19 (0.46-3.05) for female participants, respectively. Participants with a body mass index of <22 kg/m2 had a significantly higher HR, forming a U-shaped curve for the first (HR, 7.59; 95% CI, 2.13-27.0) and fifth quintiles (HR, 2.93; 95% CI, 1.05-8.18) relative to the reference. Percentage change in SUA is independently and significantly associated with future all-cause mortality among community-dwelling persons.

DOI： 10.1155/2023/7382320

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BACKGROUND: In Japan, community medicine clerkships facilitate positive attitudes toward rural medical practice and encourage rural recruitment. Rural self-efficacy has been shown to influence rural career intent following a rural clinical placement. However, the impact of subjective difficulties of living in a rural area on future rural career intent is also important. This study aims to explore whether rural self-efficacy influences the relationship between difficulty with living in a rural area and rural career intent.  METHODS: The subjects included 308 male and 255 female participants aged 20-41 [median (interquartile range): 22 (21-22)] years. Rural self-efficacy was based on a validated scale consisting of 15 questions. Difficulty with living in a rural area was measured asking students. A cohort survey was conducted to evaluate the effect of the rural self-efficacy score on the rural career intent of Japanese medical students after they completed their rural clinical training. RESULTS: The following variables were significantly associated with a higher rural self-efficacy score: female sex (p = 0.003), age < 21 years (p = 0.013), having a doctor as a role model (p < 0.001), gaining admission through a school recommendation (p = 0.016), living in a rural or remote area until the age of 18 years (p = 0.018), and orientation towards general medicine (p < 0.001). In addition, baseline difficulty with living in a rural area was significantly associated with a lower self-efficacy score (p < 0.001). Participants with a stronger intent to practice in a rural area before rural clinical training had higher rural self-efficacy and showed a stronger positive rural career intent after rural clinical training (p < 0.001). A multivariable logistic regression analysis demonstrated that difficulty with living in a rural area [odds ratio (OR): 0.61; 95% confidence interval (CI), 0.39-0.84] was still associated with lower rural career intent after rural clinical training, independent of all confounders such as gender, age, scholarship for regional duty, rural background, and orientation towards general medicine. However, when rural self-efficacy (OR, 1.12; 95% CI, 1.07-1.16) was added as a factor for rural career intent, difficulty with living in a rural area (OR, 0.68; 95% CI, 0.43-1.06) was no longer observed as an associated factor. CONCLUSION: Subjective difficulty with living in a rural area was shown to reduce future rural career intent, but high rural self-efficacy ameliorated this decline.

DOI： 10.1186/s12909-022-03511-7

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BACKGROUND: Serum uric acid (SUA) is a key determinant of cardiovascular diseases (CVDs). Studies have also shown that SUA independently impacts age-related health outcomes, although their findings differ between males and females. Furthermore, predictive data on all-cause mortality remain limited, particularly for the Japanese population. Thus, this study examined the association between SUA and survival prognosis among males and females based on a follow-up period of 7 or 19 years. METHODS: The study was based on 1,573 male (63 ± 14 years) and 1,980 female (65 ± 12 years) participants who participated in a Nomura Cohort Study in 2002 (Cohort 1) and 2014 (Cohort 2), and continued throughout the follow-up period. A basic resident register was referenced to derive the adjusted relative risk estimates for all-cause mortality. Finally, a Cox proportional hazards model analysis was conducted and was adjusted for possible confounders to estimate hazard ratios (HRs). 95% confidence intervals (CIs) were computed separately for male and female participants. RESULTS: Of the total 3,553 participants, 905 (25.5%) were deceased. Of these, 473 were male (30.1% of all males) and 432 were female (21.8% of all females). Hyperuricemia was defined in males with SUA levels of 8.5 mg/dL or higher, and in females with SUA levels of 7.5 mg/dL or higher, and was associated with a significantly increased HR for all-cause mortality (males: 1.67; 95% CI: 1.06-2.63; females: 2.17; 95% CI: 1.20-3.94). The data were further stratified based on age (< 65 years or ≥ 65 years), body mass index (BMI) (< 25.0 kg/m2 or ≥ 25.0 kg/m2), History of cardiovascular disease, estimated glomerular filtration rate (< 60 mL/min/1.73 m2 or ≥ 60 mL/min/1.73 m2), and presence of SUA-lowering medication. All stratified groups demonstrated a similar trend. The hyperuricemia group in particular reported a significant increase in HR. On the other hand, a U-shaped increase in HR was observed in those with BMI greater than 25 kg/m2 and SUA-lowering medication, but interaction effect was not significant. CONCLUSIONS: Hyperuricemia is a key risk indicator for all-cause mortality in male and female community-dwelling individuals in Japan.

DOI： 10.1016/j.metop.2022.100186

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BACKGROUND: This study examined the relationship between survival prognosis and alanine aminotransferase (ALT), a critical factor contributing to aging-related health and mortality. The research is based on a follow-up study with 6- and 10-year intervals. METHODS: The participants included 1,610 males (63 ± 14 years old) and 2,074 females (65 ± 12 years old) who were part of the Nomura cohort study conducted in 2002 (first cohort) and 2014 (second cohort). The multivariable-adjusted hazard ratios (HRs) of death between the baseline health checkup and the end of the follow-up periods were estimated using a Cox proportional hazards model, controlling for potential confounding factors. RESULTS: The follow-up survey revealed 180 male deaths (11.2% of male participants) and 146 female deaths (7.0% of female participants). The univariate Cox regression analysis showed a significant increase in the HRs of all-cause mortality with decreasing ALT levels (p < 0.001). Furthermore, compared with individuals with ALT levels of 20-29 IU/L, the multivariable-adjusted HRs (95% confidence interval) for all-cause mortality were 2.73 (1.59-4.70) for those with ALT levels <10 IU/L, 1.45 (1.05-2.00) for those with ALT levels of 10-19 IU/L, and 1.63 (1.05-2.53) for those with ALT levels ≥30 IU/L. CONCLUSIONS: Our findings show that abnormally low ALT levels and high within the normal range were related to all-cause mortality in Japan's community-dwelling individuals. Especially, ALT activity may be an important biomarker for predicting the long-term survival of older adults.

DOI： 10.1002/jcla.24445

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Language：Japanese   Publisher：愛媛医学会  

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BACKGROUND: Serum uric acid (SUA) is a key risk factor contributing to renal failure, a serious public health problem. However, few studies have examined whether the interactive relationship between alcohol consumption and SUA is independently associated with the estimated glomerular filtration rate (eGFR). METHODS: Our sample comprised 742 men aged 69 ± 11 years (mean ± standard deviation) and 977 women aged 69 ± 10 years from a rural area. We cross-sectionally examined the relationships between the confounding factors of alcohol consumption and SUA with renal function denoted by eGFR estimated using CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations modified by a Japanese coefficient. RESULTS: In both genders, eGFR increased with a rise in alcohol consumption. This tendency was more pronounced in participants with hyperuricemia, where SUA was greater than 7.0 mg/dL in men and greater than 6.0 mg/dl in women (men: F = 41.98, p < 0.001; women: F = 41.98, p < 0.001). A multiple linear regression analysis showed that alcohol consumption (men: β = 0.112, p < 0.001; women: β = 0.060, p = 0.011) and SUA (men: β = -0.282, p < 0.001; women: β = 0.317, p < 0.001) were significantly and independently related to eGFR. Further, the interactive relationship between alcohol consumption and SUA (men: F = 6.388, p < 0.001; women: F = 5.368, p < 0.001) was a significant and independent indicator of eGFR. CONCLUSIONS: These results suggested that alcohol consumption and SUA were synergistically associated with renal dysfunction among community-dwelling persons.

DOI： 10.1002/jcla.23812

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A 62-year-old woman presented with a dry cough lasting 18 months. She had previously been examined by multiple doctors, but no abnormalities were observed. Several medications such as rabeprazole and inhaled corticosteroids were administered as test treatments without any improvement. Therefore, the possibility of biological disease, including acid reflux, had been mistakenly ruled out. We examined the sputum gram stain. The result showed phagocyted normal bacterial flora, suggesting aspiration. Laryngoscopy revealed edema of the arytenoid cartilage. The patient was finally diagnosed with laryngopharyngeal reflux and silent aspiration. This case suggested that the ineffectiveness of proton-pump inhibitors cannot always exclude the presence of reflux disease and the usefulness of gram stain examination to detect silent aspiration.

DOI： 10.1002/jgf2.348

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PURPOSE: Body mass index (BMI) is a simple index of weight-to-height that is commonly used to classify people as underweight, overweight or obesity, and high BMI has been clearly linked to increased risk of illness in adults. However, few studies have examined the significance of upper normal weight as a risk factor for the development of chronic kidney disease (CKD) in the general Japanese population. METHODS: We conducted a prospective cohort study designed as part of the Nomura study. We recruited a random sample of 421 men aged 67 ± 10 (mean ± standard deviation; range 24-95) years and 565 women aged 68 ± 9 (22-84) years during their annual health examination in a single community. We examined the relationship between quartiles of baseline BMI and renal dysfunction after a 3-year evaluation based on estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations modified by the Japanese coefficient. CKD was defined as having dipstick-positive proteinuria (≥ 1 +) or a low eGFR (< 60 mL/min/1.73 m2). RESULTS: Of the 986 participants, a total of 134 (13.6%) participants, including 72 (17.1%) men and 62 (11.0%) women, received a new diagnosis of CKD during the study period, and 25 (9.7%), 19 (8.0%), 47 (19.0%), and 43 (17.8%) diagnoses were received in the BMI-1 (BMI, < 20.7 kg/m2), BMI-2 (BMI, 20.7 to 22.5 kg/m2), BMI-3 (BMI, 22.6 to 24.4 kg/m2), and BMI-4 (BMI ≥ 24.5 kg/m2) groups, respectively. Using BMI-2 as the reference group, the non-adjusted odds ratio (OR) (95% confidence interval) for CKD was 2.70 (1.53-4.75) for BMI-3 and 2.49 (1.40-4.42) for BMI-4, and the multivariable-adjusted OR was 2.52 (1.40-4.56) for BMI-3 and 2.30 (1.26-4.22) for BMI-4. CONCLUSIONS: Increased BMI from upper normal weight is strongly associated with the development of CKD in community-dwelling persons.

DOI： 10.1007/s11255-020-02501-2

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Background: The risk associated with serum uric acid (SUA) levels when within the normal range is unknown. This study aims to examine whether SUA within the normal range is a predictor of hypertension. Methods: The subjects comprised 704 men aged 71 ± 9 (mean ± standard deviation) years and 946 women aged 70 ± 8 years recruited for a survey at the community based annual medical check-up. The main outcome was the presence of hypertension (antihypertensive medication and/or having SBP ≥140 mmHg and/or DBP ≥90 mmHg). Results: At baseline, 467 (66.3%) men and 608 (64.3%) women had hypertension. Comparing to lowest quartile in women (SUA-1, uric acid < 4.1 mg/dL), the unadjusted odds ratios (ORs) [95% confidence interval (CI)] for hypertension of SUA-2 (4.1 to 4.7 mg/dL), SUA-3 (4.8 to 5.4 mg/dL), and SUA-4 (≥5.5 mg/dL) were 1.11 (0.78-1.59), 1.75 (1.20-2.55), and 1.89 (1.30-2.77), respectively. These associations were apparent even after adjustments for age, but ORs were attenuated after adjusting for all confounding factors. During a follow-up of 3.0 years, there were 35 (24.0%) hypertension cases in men and 51 (20.8%) in women. In women only, a significant association between increased SUA categories and incidence of hypertension was observed, and the multivariate-ORs (95% (CI) for incident hypertension of SUA-3 (4.5-5.2 mg/dL) and SUA-4 (≥5.3 mg/dL) were 2.23 (0.81-6.11) and 3.84 (1.36-10.8), respectively. Conclusions: These results suggest that baseline SUA within the normal range could be an important predictor for incidence of hypertension in Japanese community-dwelling elderly women.

DOI： 10.1186/s40885-020-00155-x

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Background: The incidence of hypertension is increasing worldwide and obesity is one of the most significant risk factors. Obesity can be defined by various anthropometric indices such as body mass index (BMI), waist-to-hip ratio (WHpR), and waist-to-height ratio (WHtR). This study examined a range of anthropometric indices and their relationships with hypertension. Methods: This study included 768 men aged 70 ± 10 years and 959 women aged 70 ± 8 years from a rural village. The relationship between anthropometric indices (BMI, WHpR, and WHtR) and hypertension was examined using cross-sectional (baseline, N = 1727) and cohort data (follow-up, N = 419). Receiver operating characteristic (ROC) analysis was used to determine the predictive ability of obesity indices for hypertension in both genders. Logistic regression models were used to evaluate WHtR as a significant predictor of hypertension. Results: In the cross-sectional study, WHtR, BMI, and WHpR showed significant predictive abilities for hypertension in both genders, with WHtR showing the strongest predictive ability. Also, in the cohort study, WHtR showed a significant predictive ability for incident hypertension in both genders, and, for women, BMI as well as WHtR had also predictive ability. In the cross-sectional study, the optimal WHtR cutoff values were 0.53 (sensitivity, 44.3%; specificity, 80.2%) for men and 0.54 (sensitivity, 60.9%; specificity, 68.6%) for women. In the cohort study, the optimal WHtR values were 0.47 (sensitivity, 85.4%; specificity, 39.8%) for men and 0.51 (sensitivity, 66.7%; specificity, 58.2%) for women. Conclusions: The results suggest that WHtR is a useful screening tool for hypertension among Japanese middle-aged and elderly community-dwelling individuals.

DOI： 10.1186/s40885-020-00142-2

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

PURPOSE: Neutrophil-to-lymphocyte ratio (NLR) was widely studied as a prognostic marker in various medical and surgical specialties, but its significance in diabetic kidney disease is not yet established. METHODS: The subjects comprised 199 men aged 73 ± 11 (mean ± standard deviation) years and 187 women aged 77 ± 10 years from a rural hospital. We examined the relationship between NLR calculated by analyzing differential leukocyte count in complete blood picture and renal function evaluated by estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease Study Group equation and urinary albumin excretion (UAE). RESULTS: NLR was negatively related to eGFR and positively related to UAE. Multiple linear regression analysis using eGFR and UAE as an objective variables, adjusted for confounding factors as explanatory variables showed that NLR (β = - 0.101, p = 0.009) as well as age, body mass index, serum uric acid, and presence of uric acid lowing medication were significantly and independently associated with eGFR, and NLR (β = 0.113, p = 0.031) as well as prevalence of cardiovascular disease, systolic blood pressure, presence of antihypertensive medication, presence of antilipidemic medication, and eGFR were significantly and independently associated with UAE. The multivariate-adjusted odds ratios (95% confidence interval) of NLR for stage 3a (eGFR < 60 mL/min/1.73 m2), stage 3b (eGFR < 45 mL/min/1.73 m2), and microalbuminuria (UAE ≥ 30 mg/g Cr) were 1.90 (1.02-3.56) and 2.99 (1.28-6.98), and 1.77 (1.04-3.01), respectively. Next, to examine the consistency of the observed association between NLR and eGFR, we performed subgroup analyses. There was a significant interaction (p = 0.006) only between the two groups regarding antihypertensive medication (absence: β = - 0.272, p < 0.001 and presence: β = - 0.029, p = 0.564). CONCLUSIONS: Our data suggested that NLR might be important as a potential factor for evaluating patients with a higher degree of albuminuria among diabetic outpatients.

DOI： 10.1007/s11255-018-02065-2

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Language：Japanese   Publishing type：Research paper (scientific journal)  

AIM: In Japan, the imbalance in the medical workforce has caused a deterioration of rural medicine. We explored the differences in speciality preferences and career determinant factors among students to identify keys to increase the recruitment of physicians to rural areas. METHODS: We conducted a survey of first- and fifth-year medical students, using a questionnaire enquiring about their specialty preference and career determinant factors. The data were analyzed with a chi-square test. RESULTS: A higher percentage of first-year students preferred to be basic medicine scientists, while fifth-year students considered internal medicine subspecialities, obstetrics and gynecology, anesthesia, and ophthalmology to be the most desirable. The factor analysis yielded five factors responsible for these findings; high social approval of the specialty, working hours, income, advice from senior classmates and doctors, and the work environment. The percentage of students who considered rural practice as a choice for thier future plan and had an awareness of the collapse of rural medicine was lower in the fifth-year students than in the first-year students. CONCLUSION: To increase the medical work force in provincial areas, it is necessary to strengthen not only the medical system with regard to general medicine, but also to offer better medical education in rural areas. More information about rural practice should therefore be transmitted to medical students.

DOI： 10.3143/geriatrics.52.48

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