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As part of their continuous effort to enhance the effectiveness and democratic legitimacy of human rights treaties, human rights treaty organs have increasingly fostered a direct relationship with various state organs, thereby penetrating the ‘states’ that traditionally have been treated as monolithic legal entities. Treaty organs review the decision-making process of each type of state organ – courts, parliaments and administrative organs – and make remedial orders that are substantially addressed to specific state organs. Such phenomena go hand in hand with the relativization of the distinction between the legal spheres in which human rights treaty organs and state organs operate. This is the first study to address such phenomena as a totality. It constructs the ‘separation of powers in a globalized democratic society’ theory, thereby proposing how each type of state organ and the treaty organs should interact under human rights treaties. Its findings contribute, first, to the harmonious achievement of the effectiveness and democratic legitimacy of human rights treaties; second, to the reform of the classical paradigm of international law, in which monolithic states are the only relevant legal entities; and third, to the long-standing debates on the relationship between international and national laws from a new angle.

By addressing the question “Are the roles and values of stakeholder participation qualitatively different for non-governmental organizations (NGOs) and national human rights institutions (NHRIs), and if so, how?” this article dissects stakeholder participation in UN human rights treaty body activities. First, it normatively posits that stakeholder participation in treaty body activities carries three values, which weigh differently based on the actor and the treaty body activity concerned: facilitating “bounded” national deliberations, promoting international deliberations on human rights treaty standards, and supplementing the treaty bodies’ fact-finding capacity. It offers concrete normative guidance for treaty bodies on their engagement with NGO and NHRI participation to maximize the benefits of these values. It then empirically analyzes their current practice in light of the above-mentioned normative guidance. This article contributes, first, to the theorization of stakeholder participation in treaty body activities, which has been discussed but only in generalized or fragmented ways in previous studies. Second, it supports the effectiveness and legitimacy of treaty bodies by endorsing their practice that is consistent with the guidance and finding space for improvement. Finally, it provides a rationale for establishing and strengthening NHRIs by showing that NHRI participation has unique roles distinct from those of NGOs.

Steatosis, or ectopic lipid deposition, is the fundamental pathophysiology of non-alcoholic steatohepatitis and chronic kidney disease. Steatosis in the renal tubule causes endoplasmic reticulum (ER) stress, leading to kidney injury. Thus, ER stress could be a therapeutic target in steatonephropathy. Five-aminolevulinic acid (5-ALA) is a natural product that induces heme oxygenase (HO)-1, which acts as an antioxidant. This study aimed to investigate the therapeutic potential of 5-ALA in lipotoxicity-induced ER stress in human primary renal proximal tubule epithelial cells. Cells were stimulated with palmitic acid (PA) to induce ER stress. Cellular apoptotic signals and expression of genes involved in the ER stress cascade and heme biosynthesis pathway were analyzed. The expression of glucose-regulated protein 78 (GRP78), a master regulator of ER stress, increased significantly, followed by increased cellular apoptosis. Administration of 5-ALA induced a remarkable increase in HO-1 expression, thus ameliorating PA-induced GRP78 expression and apoptotic signals. BTB and CNC homology 1 (BACH1), a transcriptional repressor of HO-1, was significantly downregulated by 5-ALA treatment. HO-1 induction attenuates PA-induced renal tubular injury by suppressing ER stress. This study demonstrates the therapeutic potential of 5-ALA against lipotoxicity through redox pathway.

Water is an essential nutrient for all organisms and is important for maintaining life and health. We aimed to develop a biomarker-calibrated equation for predicting water turnover (WT) and pre-formed water (PW) using the doubly labelled water (DLW) method. Cross-sectional study. General older population from the Kyoto-Kameoka Study, Japan. The 141 participants aged ≥ 65 years were divided into a model developing ( 71) and a validation cohort group ( 70) using a random number generation. WT and PW was measured using the DLW method in May-June of 2012. In developing the cohort, equations for predicting WT and PW were developed by multivariate stepwise regression using all data from the questionnaires in the Kyoto-Kameoka study (including factors such as dietary intake and personal characteristics). WT and PW measured using the DLW method were compared with the estimates from the regression equations developed using the Wilcoxon signed-rank test and correlation analysis in validation cohort. The median WT and PW for 141 participants were 2·81 and 2·28 l/d, respectively. In the multivariate model, WT ( = 0·652) and PW ( = 0·623) were moderately predicted using variables, such as height, weight and fluid intake from beverages based on questionnaire data. WT ( = 0·527) and PW ( = 0·477) predicted that using this model was positively correlated with the values measured by the DLW method. Our results showed factors associated with water requirement and indicated a methodological approach of calibrating the self-reported dietary intake data using biomarkers of water consumption.

PurposeWhile the association between diet quality and mortality has been previously demonstrated, the association between frailty and diet quality has not been evaluated well. This study aimed to investigate the association between diet quality and prevalence of both physical and comprehensive frailty, using two validated tools, in a community-based cohort of older adults.MethodsWe conducted cross-sectional analyses using baseline data of 7022 participants aged ≥ 65 years in the Kyoto-Kameoka study. Diet quality was assessed by calculating the adherence scores to the Japanese Food Guide Spinning Top using a validated questionnaire; the participants were stratified into quartile groups based on these scores. Physical and comprehensive frailty was assessed using the Fried phenotype model-based Frailty Screening Index and the Kihon Checklist, respectively. Multivariable logistic regression and the restricted cubic spline model were used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs) for associations between adherence scores and frailty prevalence.ResultsHigher adherence scores signified a higher intake of vitamin C, vegetables, dairy products, and fruits. Physical and comprehensive frailty prevalence was 14.2 and 35.8%, respectively. In a multivariable adjusted model, compared with the bottom adherence score quartile, the top quartile was associated with lower ORs of physical (OR 0.64; 95% CI 0.52–0.80) and comprehensive frailty (OR 0.60; 95% CI 0.51–0.71). These relationships were similar to results in the spline model.ConclusionsThis study shows an inverse dose–response relationship between diet quality and prevalence of both physical and comprehensive frailty in older adults.

Although better diet quality is inversely related to the risk of geriatric disorders, the association of adherence to dietary guidelines with oral health-related quality of life (OHRQoL) is unclear. We aimed to investigate this association in older Japanese adults. This cross-sectional study included 7984 Japanese participants aged ≥ 65 years from the population-based Kyoto–Kameoka study. Dietary intake was estimated using a validated self-administered FFQ. The scores for adherence to the Japanese Food Guide Spinning Top (range: 0 (worst) to 80 (best)) were calculated. These scores were stratified into quartiles (Qs). Poor OHRQoL was defined as a score ≤ 50 using a 12-item Geriatric Oral Health Assessment Index. The OR and 95 % CI were calculated using multivariable logistic regression and the spline model. Higher adherence score was associated with a lower prevalence of poor OHRQoL (Q1–Q4:36·0 %, 32·1 %, 27·9 % and 25·1 %, respectively). An inverse association was found between the score for adherence to the food-based Japanese dietary guidelines and the OR of poor OHRQoL among all the participants (Q1: reference; Q2: OR, 0·87 (95 % CI: 0·75, 1·00); Q3: OR, 0·77 (95 % CI: 0·66, 0·90); Q4: OR, 0·72 (95 % CI: 0·62, 0·85); P for trend < 0·001). These relationships were similar to the results in the spline model. Higher adherence to the food-based Japanese dietary guidelines is inversely associated with the prevalence of poor OHRQoL in older adults. Our results may provide useful insights to improve and maintain oral health.

To determine the association between geriatric disorders and dietary intake, validation of a food frequency questionnaire (FFQ) for elderly individuals is needed. We compared energy and nutrient intakes derived from dietary records (DR) and FFQ in an elderly population and compared the data against results from middle-aged individuals (30–68 years) from a previous study. Current participants included 65 women and 78 men (65–88 years) who completed FFQ and 7-day DR in a subpopulation of the Kyoto-Kameoka study. Our FFQ was created for middle-aged individuals. To validate the FFQ, we investigated equivalent precision by comparing the correlation coefficients between the present and previous study. Median correlations for energy and nutrient intake between the DR and FFQ in the current and previous studies were 0.24 and 0.30 (p = 0.329) in women and 0.24 and 0.28 (p = 0.399) in men, respectively. The median ratio of FFQ to DR for these intakes were also similar. The accuracy and precision of the FFQ for energy and nutrient intake in elderly individuals did not differ compared with previous findings in a middle-aged population. A validation study evaluating energy and nutrient intake using recovery biomarkers is further needed.

Background Hypertension is one of the major etiologies that cause chronic kidney disease (CKD) and can exacerbate kidney dysfunction. Zinc is an essential trace element playing a role in blood pressure regulation, and zinc deficiency, a common comorbidity in patients with CKD, can cause hypertension. However, the precise mechanism underlying zinc deficiency-induced hypertension is unknown. Sodium (Na + ) retention due to inappropriate Na + reabsorption in the renal tubule is the principal pathophysiology of hypertension. Therefore, this study aimed to investigate the association between zinc deficiency and salt sensitivity. Methods Adult mice were fed a zinc-adequate (ZnA) or zinc-deficient (ZnD) diet combined with/without high salt in drinking water (HS) for 4 weeks ( n  = 6 each). Changes in blood pressure, urinary sodium excretion, and the expressions of the proximal tubular Na + transporter, Na + /H + exchanger 3 (NHE3), which mostly contributes to filtered Na + reabsorption and the downstream Na + –Cl − transporter (NCC) were analyzed. Results Urinary Na + excretion significantly increased in ZnD mice, indicating that zinc deficiency causes natriuresis. NHE3 expressions were significantly suppressed, whereas NCC was upregulated in ZnD mice. Interestingly, the combination of high salt and ZnD diet (HS-ZnD) reversed the urinary Na + loss. The NCC remained activated and NHE3 expressions paradoxically increased in HS-ZnD mice compared with those fed the combination of high salt and ZnA diet. In addition, blood pressure significantly increased only in HS-ZnD mice. Conclusion The combination of zinc deficiency and high salt causes hypertension. Zinc is associated with salt-sensitivity, potentially through NHE3 and NCC regulation.

Self-reported energy intake (EI) estimation may incur systematic errors that could be attenuated through biomarker calibration. We aimed to confirm whether calibrated EI was comparable to total energy expenditure (TEE) measured using the doubly labelled water (DLW) technique. Cross-sectional study. General older population from the Kyoto-Kameoka Study, Japan. This study included sub- and main cohorts of 72 and 8058 participants aged≥ 65 years, respectively. EI was evaluated using a validated FFQ, and calibrated EI was obtained using a previously developed equation based on the DLW method. TEE was considered representative of true EI and also measured using the DLW method. We used a Wilcoxon signed-rank test and correlation analysis to compare the uncalibrated and calibrated EI with TEE. In the sub-cohort, the median TEE, uncalibrated EI and calibrated EI were 8559 kJ, 7088 kJ and 9269 kJ, respectively. The uncalibrated EI was significantly lower than the TEE (median difference = -1847 kJ; interquartile range (IQR): -2785 to -1096), although the calibrated EI was not (median difference = 463 kJ; IQR: -330 to 1541). The uncalibrated ( = 0·275) and calibrated EI ( = 0·517) significantly correlated with TEE. The reproducibility was higher for calibrated EI (interclass correlation coefficient (ICC) = 0·982) than for uncalibrated EI (ICC = 0·637). Similar findings were observed when stratifying the sample by sex. For medians, uncalibrated EI was lower (about 17 %) than calibrated EI in the main cohort. Biomarker calibration may improve the accuracy of self-reported dietary intake estimation.

Background/Objectives: Renal anemia is one of the major complications associated with chronic kidney disease (CKD). Erythropoietin-stimulating agents (ESAs) are commonly used; however, some patients exhibit resistance. Hypoxia-inducible factor prolyl-hydroxylase inhibitors (HIF-PHIs) have emerged as a novel treatment for renal anemia, enhancing erythropoiesis and iron metabolism. Methods: We retrospectively analyzed laboratory data related to erythropoiesis from 105 patients with CKD before and after treatment with HIF-PHI or ESA. The dialysis initiation and mortality rates were also assessed over a median follow-up of 614 days. Results: HIF-PHI and ESA significantly increased the hemoglobin levels within 6 months of treatment (9.5 ± 1.0 to 10.7 ± 1.1, p < 0.01, and 9.9 ± 1.5 to 10.7 ± 1.2 g/dL, p < 0.01, respectively). The HIF-PHI group demonstrated a significant decrease in red cell distribution width (14.5 ± 1.9% to 13.8 ± 1.4%, p < 0.01), suggesting improved erythropoiesis, and exhibited a lower cumulative incidence of outcomes. The aged-adjusted multivariate analysis confirmed the independent association between HIF-PHI treatment and reduced risk of cumulative outcome (p = 0.042). Conclusions: HIF-PHIs can serve as an alternative to ESA for managing renal anemia in CKD, improving both hematological parameters and long-term outcomes.