Masaru Sakurai

Cadmium (Cd), a widespread pollutant, is primarily absorbed via diet and smoking. Chronic Cd exposure has been associated with various adverse health effects, including renal tubular and skeletal damage. Urinary Cd concentration accurately reflects cumulative Cd exposure owing to its strong correlation with renal cortical Cd levels. This study evaluated the accuracy of estimated lifetime Cd intake by examining its correlation with urinary Cd levels after soil remediation, an aspect unreported even in the Kakehashi River Basin. A total of 565 men and 450 women were included. Lifetime Cd intake (g) was estimated using an established exposure assessment model that incorporated individual residential history, rice Cd concentrations, and dietary assumptions. Urinary Cd concentrations were determined using inductively coupled plasma mass spectrometry. Linear regression analyses were conducted between lifetime cadmium intake and urinary cadmium concentration. The obtained standardized regression coefficients were 0.49 for men and 0.54 for women (both p < 0.001), indicating strong associations. Despite possible exposure misclassification, these findings support the utility of lifetime cadmium intake as a useful surrogate indicator of cumulative cadmium exposure and provide further evidence for its application in risk assessment and the derivation of tolerable cadmium intake values.

Background: Lymph‐node‐first presentation of Kawasaki disease (NFKD) initially manifests as fever and cervical lymphadenopathy, mimicking bacterial cervical lymphadenitis (BCL). However, studies of diagnostic markers have yielded inconsistent results, and data from Japanese cohorts remain limited. Methods: This single‐center retrospective study included 151 patients with Kawasaki disease (KD) (typical KD [tKD], n = 104; NFKD, n = 47) and 21 patients with BCL. We compared clinical characteristics, pretreatment laboratory values, and imaging findings among the tKD, NFKD, and BCL groups. Results: Compared with BCL, NFKD was associated with older age, higher C‐reactive protein, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels, and lower albumin levels. Patients with BCL had higher white blood cell (WBC) and platelet counts and more frequent imaging findings suggestive of abscess formation. Multivariable analysis showed that older age, elevated AST levels, hypoalbuminemia, and lower WBC count were factors associated with NFKD. Receiver operating characteristic analysis yielded exploratory cutoff values of age ≥ 29 months, WBC ≤ 13.02 × 10 ³ /μL, AST ≥ 35 U/L, and albumin ≤ 3.8 g/dL. Compared with tKD, patients with NFKD were older, had a longer interval from symptom onset to diagnosis, and a higher rate of incomplete KD. Coronary artery involvement and intravenous immunoglobulin responsiveness were similar between the two KD groups. Conclusions: NFKD is a KD phenotype that mimics BCL in its local presentation but shares clinical features with tKD. In children with fever and cervical lymphadenopathy, older age, modest leukocytosis, elevated AST levels, and hypoalbuminemia may help raise clinical suspicion for NFKD.

This study explored the effects of soil restoration on cadmium (Cd) body burden and renal tubular damage in inhabitants of Cd-polluted areas by estimating the lifetime Cd (LCd) intake and expected LCd intake without soil restoration. In total, 1819 participants (991 men and 828 women) were included in the analysis. Furthermore, 845 participants (503 men and 342 women) who had lived in Cd-polluted areas before soil restoration were selected to estimate LCd intake with and without soil restoration. LCd intake was estimated based on residential history and rice Cd concentrations in each area. First morning urine samples were collected for urinary Cd (U-Cd, as the Cd body burden) and β2-microglobulin (as the renal tubular marker) measurements. The mean LCd intake was 3.0 g for men and 2.6 g for women in Cd-polluted areas with soil restoration. The mean expected LCd intake without soil restoration was 5.1 g for men and 4.6 g for women, indicating that soil restoration reduced LCd intake by approximately 2 g for both sexes. Soil restoration significantly reduces LCd intake, Cd body burden, and renal tubular effects. This information is crucial for developing strategies to reduce Cd exposure worldwide.

Aims/hypothesis: We aimed to investigate the association between reversion to normoglycaemia among individuals with prediabetes (fasting plasma glucose 5.6–6.9 mmol/l in the absence of other criteria for type 2 diabetes) and the subsequent risk of type 2 diabetes, and to examine whether concurrent favourable cardiometabolic risk factor profiles modify this association. Methods: We used individual-level data from prospective cohorts in the USA, Australia and Asia. Participants with prediabetes at baseline, with at least two follow-ups ( n =8191) at median intervals of 2.9 years (IQR 2.3–9.0) and 3.1 years (IQR 2.6–3.6), were classified into restoration of normoglycaemia and persistent prediabetes groups based on the glucose status at the first follow-up (normoglycaemia or prediabetes). Type 2 diabetes occurrence was assessed at subsequent follow-ups. Hierarchical mixed-effects proportional hazards Weibull models estimated type 2 diabetes risk, adjusting for age, sex and cardiometabolic risk factors. A subgroup analysis evaluated the combined association of normoglycaemia restoration and normal cardiometabolic risk factor levels on subsequent type 2 diabetes risk. Results: In individuals with prediabetes, normoglycaemia restoration compared with persistent prediabetes was associated with a 51% lower risk of developing type 2 diabetes. Even lower risks were observed among individuals with concurrent favourable cardiometabolic profiles, including non-smokers (HR 0.20, 95% CI 0.10, 0.31), and those with normal BMI (0.16, 95% CI 0.06, 0.27), waist circumference (0.22, 95% CI 0.12, 0.33), waist-to-height ratio (0.15, 95% CI 0.03, 0.26), WHR (0.17, 95% CI 0.05, 0.28), and systolic (0.20, 95% CI 0.11, 0.30) and diastolic (0.25, 95% CI 0.12, 0.38) blood pressure, triacylglycerol (0.24, 95% CI 0.13, 0.35) and HDL-cholesterol levels (0.21, 95% CI 0.13, 0.29). Weight loss combined with normoglycaemia restoration was also associated with lower type 2 diabetes risk (0.18, 95% CI 0.07, 0.30) compared with weight gain and persistent prediabetes. Conclusions/interpretation: Our results suggest that prioritising normoglycaemia restoration during the prediabetes stage in clinical guidelines may contribute to reducing the risk of type 2 diabetes, particularly when accompanied by favourable cardiometabolic health profiles. Graphical

Objectives: Previous research has indicated that shift workers exhibit fewer healthy behaviors than those working regular daytime hours. Although health literacy influences health behaviors, studies comparing health literacy levels between shift and fixed-day workers and investigating whether differences in health behaviors between these 2 groups are mediated by health literacy are lacking. Methods: This cross-sectional study used a self-administered questionnaire in a large-scale manufacturing company. Overall, 2152 manual workers aged 18-64 years were enrolled in this study (961 and 1191 fixed-day and shift workers, respectively). Logistic regression structural equation models were used for analyzing the mediating role of health literacy in the relationship between shift work and health behaviors. Results: Shift and fixed-day workers did not show differences in age-adjusted health literacy. Compared with fixed-day workers, the odds ratios of shift workers for leisure time exercise, not currently smoking, having breakfast, brushing their teeth, and eating green and yellow vegetables were 0.85 (95% CI, 0.70-1.02), 0.68 (95% CI, 0.56-0.80), 0.63 (95% CI, 0.52-0.76), 0.79 (95% CI, 0.65-0.95), and 0.58 (95% CI, 0.48-0.70), respectively. Mediation analysis showed that the odds ratios of the direct effects of shift work on favorable habits were almost the same as the total effect. Conclusions: This study observed that health literacy did not mediate health behavior and shift work. Further research is needed to clarify the causes of these differences.

Inflammation and oxidative stress are crucial for osteoarthritis (OA) pathogenesis. Despite the potential of pharmacological pretreatment of chondrocytes in preventing OA, its efficacy in preventing the progression of cartilage damage and promoting its recovery has not been examined. In this study, an H₂O₂-induced human OA-like chondrocyte cell model was created using H1467 primary human chondrocytes to evaluate the efficacy of interleukin (IL)-6 and cyclooxygenase (COX)-2 inhibitors (tocilizumab and celecoxib, respectively) in the prevention and treatment of cartilage damage. H₂O₂ significantly elevated the IL-6, COX-2, and matrix metalloproteinase (MMP)-13 levels. Although monotherapy decreased the levels, nuclear shrinkage and altered cell morphology, similar to those in the H₂O₂ group, were observed. The expression of these factors was significantly lower in the combination therapy group, and the cell morphology was maintained. Moreover, the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway was activated, and levels of the antioxidant protein heme oxygenase-1 (HO-1) were increased, especially in the combination group, indicating an anti-inflammatory effect. The treatment groups, particularly the combination group, demonstrated increased cell viability. Overall, the drug combination exhibited superior efficacy in preventing the progression of cartilage damage and promoted its recovery compared with the monotherapy. Given that the drugs herein are already in clinical use, they are suitable candidates for OA treatment.

Tendinopathy is an aging-related disease, often caused by micro-scarring and degeneration due to overuse or trauma. Ascorbic acid (vitamin C) supplementation is reported to be a useful treatment for tendinopathy recovery. We compared the inhibitory effects of various ascorbic acid doses on tendon cell damage. H₂O₂ was added to human-derived tendon cells in vitro (Group H₂O₂, control), followed by incubation with 150 µM or 30 mM of ascorbic acid (Group C, Group HC). The oxidative injury degree was evaluated by determining reactive oxygen species levels. The cytoskeletal structure was examined via fluorescence immunostaining of actin filaments. Quantitative polymerase chain reaction (qPCR) was performed to analyze the expressions of mitochondria transcription factor A, adenosine triphosphate 5A, type I collagen, and p16. Cell death was reduced, and oxidative stress was inhibited in C and HC groups. The cytoskeleton was maintained in the HC group but not in the C group. qPCR analysis revealed that p16 expression was inhibited in both the C and HC groups compared to the H₂O₂ group; other markers had increased expression. The progression of cell death and cytoskeletal disruption was inhibited by the administration of high-dose vitamin C. Hence, high-dose vitamin C is a potential treatment for tendon cell degeneration.

The aim of the present study was to apply an updated benchmark dose (BMD) approach to estimate reference urinary cadmium (U-Cd) for renal tubular and glomerular effects. This cross-sectional survey was conducted 30 years ago in 30 men and 44 women living in a Cd-polluted area and in 18 men and 18 women living in a non-polluted area. We applied an updated hybrid approach to estimate the BMDs and 95% lower confidence limits (BMDLs) of U-Cd for creatinine (Cr) clearance (CrCl), estimated glomerular filtration rate (eGFR), β2-microglobulin (β2-MG), and β2-MG tubular reabsorption (%TRβ2-MG). Using a benchmark response (BMR) of 5%, we estimated the BMDLs of U-Cd for adverse renal effect markers to be 2.9 (eGFR), 1.8 (β2-MG), 1.8 (%TRβ2-MG < 95%), and 3.6 μg/g Cr (%TRβ2-MG < 90%) in men, and 3.5 (CrCl), 2.5 (β2-MG), 2.6 (%TRβ2-MG < 95%), and 3.9 μg/g Cr (%TRβ2-MG < 90%) in women. The obtained BMDLs for tubular effects were 1.8–3.6 µg/g Cr and for glomerular effects were 2.9–3.5 µg/g Cr; these are not very high compared to the exposure levels in the general population. The BMDLs calculated in this study provide important information for measures regarding protecting general inhabitants or workers from the adverse health effects of Cd exposure.