Association between oxidative balance score and inflammatory markers in middle-aged and older Japanese people.

PURPOSE: This study aimed to investigate the association between oxidative balance score (OBS), wherein higher OBSs indicate lower oxidative stress, and high-sensitivity C-reactive protein (hs-CRP), as well as inflammatory scores, in a large cohort of Japanese adults. METHODS: In total, 9703 individuals aged 40-69 years participated in a baseline survey of a population-based cohort study in Saga, Japan (2005-2007). OBSs were calculated from 11 prooxidant and antioxidant lifestyle factors, including dietary intake, physical activity, alcohol consumption, and smoking status. Lifestyle data, including dietary intake, were obtained using a self-administered questionnaire. Adjusted geometric means of serum hs-CRP levels were calculated based on OBS quartiles, and linear trend tests were performed, with adjustments for potential confounders. In addition, an inflammatory cytokine z-score was constructed and assessed alongside individual markers. RESULTS: After adjusting for multiple confounders in both sexes, the results showed a significant inverse association between OBS and serum hs-CRP levels in both men and women. These results remained unaltered when the OBS evaluation excluded powerful prooxidants, serum ferritin, or smoking. There was also an association between OBS and lower inflammatory z-score, indicating reduced overall systemic inflammation. CONCLUSIONS: These findings suggest that a higher OBS, indicating a greater predominance of antioxidants over prooxidant exposure, is associated with lower hs-CRP levels and reduced systemic inflammation, regardless of sex.

Association between the Prognostic Nutritional Index and the Occurrence of Immune-Related Adverse Events.

Immune-related adverse events (irAEs) affect all organs and are associated with various symptoms. The identification of biomarkers that can predict irAEs may be particularly clinically useful. This study aimed to investigate whether the prognostic nutritional index (PNI) before the initiation of immune checkpoint inhibitor (ICI) treatment can predict the occurrence of irAEs. We conducted a survey of 111 patients with cancer who were receiving ICI fixed-dose monotherapy at Saga University Hospital from the time each ICI became available until January 2020. We compared the PNI between the patients with and without irAE expression, established a cutoff value for PNI associated with the development of irAEs, and investigated the incidence of irAEs and progression-free survival (PFS) in groups divided by the cutoff value. Patients with irAEs had significantly higher PNI than did those without, and there was a significant association between PNI and irAEs after adjusting for potential factors (odds ratio, 1.12; 95% confidence interval, 1.03-1.21). In addition, PNI ≥44.2 was associated with a significantly higher incidence of irAEs (75.0% vs. 35.2%, p = 0.0001) and significantly longer PFS than PNI <44.2 (p = 0.025). In conclusion, pretreatment PNI may be associated with the risk of developing irAEs in patients with advanced recurrent solid tumors. When the PNI is ≥44.2, patient management is important for avoiding serious AEs because while the treatment may be effective, the occurrence of irAEs is a concern.

Monitoring of blood levels in patients administered CYP3A4 inhibitor during the maintenance phase of venetoclax administration
.

OBJECTIVE: Venetoclax, an oral B-cell lymphoma-2 inhibitor, necessitates dose adjustment when combined with a CYP3A4 inhibitor; however, the dosing regimen remains unclear on adding a CYP3A4 inhibitor after venetoclax administration. CASE SUMMARY: We present a case report of a patient who was simultaneously treated with a CYP3A4 inhibitor and a steady daily dose of venetoclax. A 30-year-old male diagnosed with acute myeloid leukemia received a combination of venetoclax and azacitidine as remission induction therapy. He was prescribed 400 mg/day venetoclax at a steady daily dose, with fosfluconazole initiated on day 18. Given that fosfluconazole can induce moderate CYP3A4 inhibitory effects, the venetoclax dosage was reduced to 200 mg/day on the same day. Despite dose reduction, plasma trough levels of venetoclax continued rising gradually. Nearly 10 days were required to decrease blood levels to a steady state. CONCLUSION: The risk of elevated venetoclax blood levels needs to be considered when initiating CYP3A4 inhibitors and reducing venetoclax dosage on the same day.

Association Between the Appendicular Extracellular-to-Intracellular Water Ratio and All-Cause Mortality: A 10-Year Longitudinal Study.

The appendicular extracellular-to-intracellular water ratio (A-E/I) is a potential marker of skeletal muscle quality, reflecting the balance of water distribution between the extracellular and intracellular compartments of the appendicular limb regions. A-E/I has been increasingly used in recent studies; however, its association with adverse outcomes remains unclear. This study investigated the potential association between A-E/I and all-cause mortality. A prospective cohort study of 8 015 middle-aged and older adults (comprised of 4 755 women, aged 45-74 years) residing in a Japanese community was conducted. The baseline assessment was performed between 2010 and 2012, and the follow-up period lasted until July 2022. A-E/I and skeletal muscle mass were measured using segmental bioelectrical impedance spectroscopy. Handgrip strength (HGS) was measured using a Smedley-type dynamometer. Lifestyle, medical history, and physical activity were assessed by questionnaire and accelerometer. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for each quartile (Q) of A-E/I were estimated using the multivariable Cox regression model. During a 10.5-year median follow-up, the mortality rates were 8.9 and 3.6 per 1 000 person-years for men (292 deaths) and women (174 deaths), respectively. A-E/I quartiles were positively associated with all-cause mortality in both sexes (men: Q1, HR: 1.0 [95% CI: reference], Q4, HR: 1.8 [1.1-2.9], ptrend < .05; women, Q4, HR: 2.2 [1.3-3.8], ptrend < .01). This association remained significant after further adjustment for skeletal muscle mass and HGS (ptrend < .05). Our findings suggest that A-E/I serves as an early predictive marker for mortality in middle-aged and older Japanese adults.

Association Between Antidiabetic Drugs and Delirium: A Study Based on the Adverse Drug Event Reporting Database in Japan.

BACKGROUND AND OBJECTIVE: Several associations between diabetes mellitus and delirium have been reported; however, they have been inconsistent, and evidence on the effects of antidiabetic medications on delirium is also limited. This study aimed to investigate whether the use of antidiabetic drugs is a risk factor for delirium development. METHODS: Using the Japanese Adverse Event Reporting Database, we analyzed 662,899 reports between 2004 and 2022. Reporting odds ratios (RORs) and 95% confidence intervals (CIs) for delirium associated with diabetes and using each antidiabetic medication were calculated after adjusting for potential confounders. RESULTS: Overall, 8892 of the reports analyzed were associated with delirium. A comparison of the incidence of delirium between patients with and without diabetes showed no significant difference, with 1.34% in patients without diabetes and 1.37% in those with diabetes. In each antidiabetic medication, signals for delirium were detected for sulfonylurea (crude ROR, 1.35; 95% CI 1.21-1.51) and insulin (crude ROR, 1.28; 95% CI 1.13-1.44). These results were maintained even after adjusting for factors with potential confounders (sulfonylurea: adjusted ROR, 1.75; 95% CI 1.54-2.00, insulin: adjusted ROR, 1.35; 95% CI 1.20-1.54). CONCLUSIONS: Our results suggest no association between diabetes and delirium; however, using sulfonylurea and insulin may be associated with delirium development. Nonetheless, these findings should be validated in future studies.

The Association between Oxidative Balance Score and Urinary Levels of 8-Hydroxydeoxyguanosine among Japanese Adults.

The oxidative balance score (OBS), wherein higher OBSs indicate lower oxidative stress, was designed to assess a composite measure of multiple pro-oxidant and antioxidant effects on an individual's oxidative stress status. This study aimed to evaluate whether OBSs were inversely associated with urinary levels of 8-hydroxydeoxyguanosine (8-OHdG)-an oxidative stress marker-among Japanese adults. This cross-sectional study was based on data obtained during 2010-2012. Overall, 7552 participants from the J-MICC Study Saga who answered a self-administered food frequency questionnaire were recruited for the final analysis. OBSs were calculated from 11 pro-oxidant and antioxidant lifestyle factors, including dietary intake, physical activity, and alcohol and smoking status. Urinary 8-OHdG values were corrected by creatinine level (ng/mg creatinine). Our findings revealed a higher total OBS was significantly associated with lower urinary 8-OHdG/creatinine levels after adjustment for covariates in men and women (p for trend < 0.01 in both sexes). We performed a multiple regression analysis of the association between OBSs and urinary 8-OHdG/creatinine levels stratified by age, body mass index (BMI), and menopausal status and found consistent negative associations in most groups for both sexes. No significant differences in the 60-64 age group for women (standardized ß = -0.09, p = 0.13) or BMI < 18.5 kg/m2 for men (standardized ß = -0.18, p = 0.17) were observed. A higher OBS had a strong inverse association with urinary 8-OHdG/creatinine levels in men and women among Japanese adults. The OBS might be a useful tool for evaluating the roles of oxidative stress-related lifestyle factors, including diet.

Association between awareness of limiting food intake and all-cause mortality: A cohort study in Japan.

BACKGROUND: Improving diets requires an awareness of the need to limit foods for which excessive consumption is a health problem. Since there are limited reports on the link between this awareness and mortality risk, we examined the association between awareness of limiting food intake (energy, fat, and sweets) and all-cause mortality in a Japanese cohort study. METHODS: Participants comprised 58,772 residents (27,294 men; 31,478 women) aged 35-69 years who completed baseline surveys of the Japan Multi-Institutional Collaborative Cohort Study from 2004 to 2014. Hazard ratios (HRs) for all-cause mortality and 95% confidence intervals (CIs) were estimated by sex using a Cox proportional hazard model, with adjustment for related factors. Mediation analysis with fat intake as a mediator was also conducted. RESULTS: The mean follow-up period was 11 years and 2,516 people died. Estimated energy and fat intakes according to the Food Frequency Questionnaire were lower in those with awareness of limiting food intake than in those without this awareness. Women with awareness of limiting fat intake showed a significant decrease in mortality risk (HR=0.73; 95% CI, 0.55 to 0.94). Mediation analysis revealed that this association was due to the direct effect of the awareness of limiting fat intake and that the total effect was not mediated by actual fat intake. Awareness of limiting energy or sweets intake was not related to mortality risk reduction. CONCLUSION: Awareness of limiting food intake had a limited effect on reducing all-cause mortality risk.

Development of a specific and sensitive sandwich enzyme-linked immunosorbent assay for the quantification of dasatinib.

This study sought to develop a specific and sensitive sandwich enzyme-linked immunosorbent assay (ELISA) for pharmacokinetic studies of dasatinib, a tyrosine kinase inhibitor. Anti-dasatinib antibodies were obtained from mice or rabbits by using two partial structures of dasatinib as haptens: 2-amino-N-(2-chloro-6-methylphenyl)-thiazole-5-carboxamide and 2-{4-(2-hydroxyethyl)-1-piperazinyl}-isonicotinic acid. The best combination of two antibodies for sandwich ELISA of dasatinib was determined using four anti-dasatinib antibodies derived from mice and rabbits. Using two dasatinib-specific rabbit antibodies, we successfully developed an ultra-specific and highly sensitive sandwich ELISA that is hardly affected by the main metabolite of dasatinib. The sandwich ELISA showed a linear detection range from 320 pg/mL to 1000 ng/mL. Serum dasatinib concentrations lower than 320 pg/mL were reproducibly measurable using the sandwich ELISA. The ELISA was specific to dasatinib and there were no cross-reactivities with the major metabolites 4'-hydroxy dasatinib and dasatinib carboxylic acid. The developed sandwich ELISA will be a valuable tool for pharmacokinetic studies of dasatinib. Furthermore, this study revealed that rabbit antibodies can sandwich drug molecules of a smaller size than mouse antibodies in sandwich ELISA.

Association between green tea and coffee consumption and body iron storage in Japanese men and women: a cross-sectional study from the J-MICC Study Saga.

Purpose: This study examined the association between daily green tea and coffee consumption and body iron stores among Japanese middle-aged and older adults. Methods: This cross-sectional study used data obtained from 2005 to 2007. A total of 10,435 participants were recruited for this study. The participants completed a validated, self-administered food frequency questionnaire on green tea and coffee consumption. A multivariate linear regression analysis was conducted to assess the relationship between green tea and coffee consumption and serum ferritin levels. Additionally, logistic regression analysis was performed to ascertain whether excessive consumption of these beverages was linked to iron deficiency. Results: We observed that higher green tea and coffee consumption was associated with lower ferritin levels in men and postmenopausal women, even after adjusting for covariates (all P for trends <0.05). Among premenopausal women, we found an inverse association between green tea consumption and serum ferritin levels, while no significant association was observed for coffee consumption after adjusting for covariates (green tea, P for trend <0.05; coffee, P for trend = 0.08). Notably, the association between these beverages and iron deficiency was found only in postmenopausal women; the odds ratios (95% confidence intervals) for iron deficiency associated with almost None, <1 cup/day, 1-2 cups/day, and ≥ 3 cups/day were 1.00 (reference), 0.78 (0.26-2.49), 1.29 (0.49-3.39), and 1.59 (0.63-4.04) (P for trend = 0.05), respectively, for green tea and 1.00, 1.32 (0.64-2.73), 1.46 (0.68-3.13), and 2.20 (1.06-4.55) (P for trend <0.01), respectively, for coffee. Conclusion: Higher green tea and coffee consumption was associated with lower serum ferritin levels in men and postmenopausal women. In premenopausal women, consumption of green tea, but not coffee, was associated with lower serum ferritin levels. However, postmenopausal women who ≥3 cups of coffee demonstrated a higher prevalence of iron deficiency compared to those who consumed almost none.

GWAS of folate metabolism with gene-environment interaction analysis revealed the possible role of lifestyles in the control of blood folate metabolites in Japanese - the J-MICC Study.

BACKGROUND: The present genome-wide association study (GWAS) aimed to reveal the genetic loci associated with folate metabolites as well as to detect related gene-environment interactions in Japanese. METHODS: We conducted the GWAS of plasma homocysteine (Hcy), folic acid (FA), and vitamin B12 (VB12) levels in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study participants who joined from 2005 to 2012, and also estimated gene-environment interactions. In the replication phase, we used data from the Yakumo Study conducted in 2009. In the discovery phase, data of 2,263 participants from four independent study sites of the J-MICC Study were analyzed. In the replication phase, data of 573 participants from the Yakumo Study were analyzed. RESULTS: For Hcy, MTHFR locus on chr 1, NOX4 on chr 11, CHMP1A on chr 16, and DPEP1 on chr 16 reached genome-wide significance (P < 5×10-8). MTHFR also associated with FA, and FUT2 on chr 19 associated with VB12. We investigated gene-environment interactions in both studies and found significant interactions between MTHFR C677T and ever drinking, current drinking, and physical activity > 33% on Hcy (ß = 0.039, 0.038 and -0.054, P = 0.018, 0.021 and < 0.001, respectively) and the interaction of MTHFR C677T with ever drinking on FA (ß = 0.033, P = 0.048). CONCLUSIONS: The present GWAS revealed the folate metabolism-associated genetic loci and gene-environment interactions with drinking and physical activity in Japanese, suggesting the possibility of future personalized CVD prevention.

Evaluation of the delirium preventive effect of dual orexin receptor antagonist (DORA) in critically ill adult patients requiring ventilation with tracheal intubation at an advanced emergency center: A single-center, retrospective, observational study.

OBJECTIVE: ICU delirium reportedly contributes to increased mortality attributed to underlying diseases, long-term cognitive decline, and increased healthcare costs. Dual orexin receptor antagonists (DORAs), suvorexant and lemborexant, have been suggested for preventing ICU delirium. Although ventilator management is a risk factor for delirium, no study has examined the efficacy of suvorexant and lemborexant in preventing delirium in critically ill patients requiring ventilation. Thus, we retrospectively evaluated the efficacy of DORA in preventing delirium in critically ill adult patients requiring ventilatory management in the emergency room. METHOD: This retrospective study included patients aged ≥18 years who were admitted to the emergency room and received ventilator support between January 2015 and April 2022. The HR (95% CI) for delirium development in patients taking DORA was estimated using a Cox proportional hazards model, which was adjusted for the patient background and concomitant medications. HRs were calculated for patients taking suvorexant and those taking lemborexant using a stratified analysis. RESULTS: Of the 297 patients included in the study, 67 were in the DORA group; 50 were on suvorexant and 17 were on lemborexant. The DORA group had a lower incidence of delirium than the control group (p < 0.0001). The risk of delirium was lower in the DORA group compared the control group (HR, 0.22; 95% CI 0.12-0.40).The risk of developing delirium was lower with suvorexant (HR 0.22; 95% CI 0.11-0.41) and lemborexant (HR 0.25; 95% CI 0.08-0.81). CONCLUSION: DORA is a promising drug that could have the potential to prevent delirium, and its efficacy in preventing delirium should be tested in randomized controlled trials in the future.

Clinical characteristics of locomotive syndrome categorised by the 25-question Geriatric Locomotive Function Scale: a systematic review.

OBJECTIVES: The purpose of this study was to compile the currently available evidence on the clinical characteristics of the locomotive syndrome (LS) categorised by the 25-question Geriatric Locomotive Function Scale (GLFS-25) and clarify its clinical usefulness for assessing mobility function. DESIGN: Systematic review. DATA SOURCES: The PubMed and Google Scholar were searched for the relevant studies on 20 March 2022. ELIGIBILITY CRITERIA: We included relevant peer-reviewed articles, available in English language, on clinical LS characteristics categorised with the GLFS-25. DATA EXTRACTION AND SYNTHESIS: Pooled ORs or mean differences (MDs) of the LS groups were calculated and compared with the non-LS groups for each clinical characteristic. RESULTS: In total, 27 studies that involve 13 281 participants (LS, n=3385; non-LS, n=9896) were examined in this analysis. Older age (MD 4.71; 95% (CI) 3.97 to 5.44; p<0.00001), female gender (OR 1.54; 95% CI 1.38 to 1.71; p<0.00001), higher body mass index (MD 0.78; 95% CI 0.57 to 0.99; p<0.00001), osteoporosis (OR 1.68; 95% CI 1.32 to 2.13; p<0.0001), depression (OR 3.14; 95% CI 1.81 to 5.44; p<0.0001), lower lumbar lordosis angle (MD -7.91; 95% CI -10.08 to -5.74; p<0.00001), higher spinal inclination angle (MD 2.70; 95% CI 1.76 to 3.65; p<0.00001), lower grip strength (MD -4.04; 95% CI -5.25 to -2.83; p<0.00001), lower back muscle strength (MD -15.32; 95% CI -23.83 to -6.81; p=0.0004), lower maximum stride (MD -19.36; 95% CI -23.25 to -15.47; p<0.00001), higher timed up-and-go (MD 1.36; 95% CI 0.92 to 1.79; p<0.00001), lower one-leg standing time (MD -19.13; 95% CI -23.29 to -14.97; p<0.0001) and slower normal gait speed (MD -0.20; 95% CI -0.22 to -0.18; p<0.0001) were found to be associated with LS. No significant differences were noted in other clinical characteristics between the two groups. CONCLUSIONS: GLFS-25 is clinically useful for assessing mobility function according to the evidence available on the clinical characteristics of LS categorised by the GLFS-25 questionnaire items until.

A Simplified Screening Tool for the One-Leg Standing Test to Determine the Severity of Locomotive Syndrome.

This study determined the cut-off time for the one-leg standing test (OLST) to simply screen the severity of locomotive syndrome (LS). We conducted this cross-sectional study on 1860 community-dwelling residents (age, 70.5 ± 9.5 years old; males, n = 826; females, n = 1034) who underwent the OLST and completed the 25-question geriatric locomotive function scale (GLFS-25). Multivariate linear regression and multivariate logistic regression analyses were conducted to assess the relationship between the OLST and the GLFS-25 score and LS after adjusting for age, sex, and body mass index. A receiver operating characteristic (ROC) curve analysis was performed to calculate the optimal cut-off time of the OLST for determining LS severity. The multivariate linear regression and multivariate logistic regression analyses showed that the OLST was significantly associated with the GLFS-25 score and a diagnosis of LS. The optimal cut-off times of the OLST to screen LS-1, LS-2, and LS-3 were 42 s (sensitivity 65.8%, specificity 65.3%), 27 s (sensitivity 72.7%, specificity 72.5%), and 19 s (sensitivity 77.4%, specificity 76.8%), respectively. We developed a simplified screening tool for the OLST to determine LS severity.

Comparison of the loci associated with HbA1c and blood glucose levels identified by a genome-wide association study in the Japanese population.

Aims: Hemoglobin A1c (HbA1c) levels are widely employed to diagnose diabetes. However, estimates of the heritability of HbA1c and glucose levels are different. Therefore, we explored HbA1c- and blood glucose-associated loci in a non-diabetic Japanese population. Methods: We conducted a two-stage genome-wide association study (GWAS) on variants associated with HbA1c and blood glucose levels in a Japanese population. In the initial stage, data of 4911 participants of the Japan Multi-Institutional Collaborative Cohort (J-MICC) were subjected to discovery analysis. In the second stage, two datasets from the Tohoku Medical Megabank project, with 8175 and 40,519 participants, were used for the replication study. Association of the imputed variants with HbA1c and blood glucose levels was determined via linear regression analyses adjusted for age, sex, body mass index (BMI), smoking, and genetic principal components (PC1-PC10). Moreover, we performed a BMI-stratified GWAS on HbA1c levels in the J-MICC. The discovery analysis and BMI-stratified GWAS results were validated with re-analyses of normalized HbA1c levels adjusted for site in addition to the above, and blood glucose adjusted for fasting time as an additional covariate. Results: Genetic variants associated with HbA1c levels were identified in KCNQ1 and TMC6. None of the genetic variants associated with blood glucose levels in the discovery analysis were replicated. Association of rs2299620 in KCNQ1 with HbA1c levels showed heterogeneity between individuals with BMI ≥ 25 kg/m2 and BMI < 25 kg/m2. Conclusions: The variant rs2299620 in KCNQ1 might affect HbA1c levels differentially based on BMI grouping in the Japanese population. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-023-00618-0.

Risk of delirium with antiepileptic drug use: a study based on the Japanese Adverse Drug Event Report database.

BACKGROUND: Antiepileptic drugs may cause delirium, and the risk may vary with each drug. However, related studies have provided inconsistent results. AIM: The aim of this study was to investigate whether the use of antiepileptic drugs is a risk factor for delirium development. METHOD: Using the Japanese Adverse Drug Event Report database, we analysed 573,316 reports pertaining to the period from 2004 to 2020. Reporting odds ratios and 95% confidence intervals of delirium associated with use of antiepileptic drugs were calculated after adjusting for potential confounders. Furthermore, for each antiepileptic drug, we performed an analysis stratified based on older age and benzodiazepine receptor agonist usage. RESULTS: There were 27,439 reports of antiepileptic drug-related adverse events. Of these, 191 reports were associated with antiepileptic drugs and delirium (crude reporting odds ratio [cROR], 1.66; 95% confidence interval [CI], 1.43-1.93). The use of lacosamide (adjusted reporting odds ratio [aROR], 2.44; 95% CI, 1.24-4.80), lamotrigine (aROR, 1.54; 95% CI, 1.05-2.26), levetiracetam (aROR, 1.91; 95% CI, 1.35-2.71), and valproic acid (aROR, 1.49; 95% CI, 1.16-1.91) was related to a significantly higher reporting odds ratio for delirium, even after adjustment for possible confounding factors. However, when used in combination with benzodiazepine receptor agonists, none of the antiepileptic drugs were found to be associated with delirium. CONCLUSION: Our study's findings suggest that antiepileptic drug usage may be associated with delirium development.

Dose-response relationship between daily step count and prevalence of sarcopenia: A cross-sectional study.

OBJECTIVES: Daily step counts are an easy-to-understand indicator of physical activity; however, there is limited evidence regarding the optimal daily step count to prevent sarcopenia. This study examined the dose-response relationship between daily step count and the prevalence of sarcopenia and explored the optimal dose. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: The study included 7949 community-dwelling middle-aged and older adults (aged 45-74 years) from Japan. MEASUREMENTS: Skeletal muscle mass (SMM) was assessed using bioelectrical impedance spectroscopy, and muscle strength was quantified through handgrip strength (HGS) measurement. Participants who exhibited both low HGS (men: <28 kg, women: <18 kg) and low SMM (lowest quartile in each sex-specific category) were defined as having sarcopenia. Daily step counts were measured for 10 days using a waist-mounted accelerometer. To examine the association between daily step count and sarcopenia, a multivariate logistic regression analysis was performed, adjusting for potential confounding factors such as age, sex, body mass index, smoking status, alcohol consumption, protein intake, and medical history. The odds ratios (ORs) and confidence intervals (CIs) were calculated based on the daily step counts categorized into quartiles (Q1-Q4). Finally, a restricted cubic spline curve was fitted to further investigate the dose-response relationship between daily step count and sarcopenia. RESULTS: The prevalence of sarcopenia in the overall participants was 3.3 % (259/7949 participants), with a mean daily step count of 7292 ± 2966 steps. Expressed in quartiles, the mean daily step counts were 3873 ± 935 steps in Q1, 6025 ± 503 steps in Q2, 7942 ± 624 steps in Q3, and 11,328 ± 1912 steps in Q4. The prevalence of sarcopenia in each quartile of daily step count was 4.7 % (93/1987 participants) in Q1, 3.4 % (68/1987 participants) in Q2, 2.7 % (53/1988 participants) in Q3, and 2.3 % (45/1987 participants) in Q4. The ORs and 95 % CIs adjusted for covariates demonstrated a statistically significant inverse association between daily step count and sarcopenia prevalence (P for trend <0.01), as follows: Q1, reference; Q2, 0.79 (95 % CI: 0.55-1.11); Q3, 0.71 (95 % CI: 0.49-1.03); Q4, 0.61 (95 % CI: 0.41-0.90). The restricted cubic spline curve indicated that the ORs leveled off at approximately 8000 steps per day, and no statistically significant decrease in ORs was observed for daily step counts above this threshold. CONCLUSIONS: The study found a significant inverse association between daily step count and the prevalence of sarcopenia, with the association plateauing when the daily step count exceeded approximately 8000 steps. These findings suggest that 8000 steps per day may be the optimal dose to prevent sarcopenia. Further intervention and longitudinal studies are needed to validate the results.

Risk factors for progression of the severity of locomotive syndrome: A two-year longitudinal observational study.

BACKGROUND: The risk factors for progression of severity of locomotive syndrome (LS) remain unclear. METHODS: We conducted a longitudinal observational study of 1148 community-dwelling residents (median age, 68.0 years old; 548 males, 600 females) from 2016 to 2018. LS was assessed by the 25-question Geriatric Locomotive Function Scale (GLFS-25), and total scores of ≤6 points, 7-15 points, 16-23 points, and ≥24 points were diagnosed as non-LS, LS-1, LS-2, and LS-3, respectively. If the LS severity in 2018 was higher than in 2016, the case was defined as progression of LS severity; otherwise, it was defined as non-progressive LS. We compared the age, gender, body mass index, smoking status, alcohol consumption, living situation, car use, chronic musculoskeletal pain, comorbidities, metabolic syndrome, physical activity, and LS severity in 2016 between the progression and non-progression groups. Furthermore, a multivariate logistic regression analysis was performed to elucidate the risk factors for progression of LS severity. RESULTS: Participants in the progression group had a significantly older age, a lower rate of car use, a higher rate of low back pain, a higher rate of hip pain, a higher rate of knee pain, a higher GLFS-25 total score, and a higher rate of LS-2 than those in the non-progression group. The multivariate logistic regression analysis revealed that older age, female gender, higher body mass index (≥25.0 kg/m2), presence of low back pain, and presence of hip pain were risk factors for the progression of LS within two years. CONCLUSIONS: To prevent the progression of LS severity, related prophylaxis strategies should be implemented, especially for individuals with the above-mentioned characteristics. Further longitudinal studies with a longer observation period are necessary.

Effects of gene-lifestyle interactions on obesity based on a multi-locus risk score: A cross-sectional analysis.

BACKGROUND: The relationship between lifestyle and obesity is a major focus of research. Personalized nutrition, which utilizes evidence from nutrigenomics, such as gene-environment interactions, has been attracting attention in recent years. However, evidence for gene-environment interactions that can inform treatment strategies is lacking, despite some reported interactions involving dietary intake or physical activity. Utilizing gene-lifestyle interactions in practice could aid in optimizing interventions according to genetic risk. METHODS: This study aimed to elucidate the effects of gene-lifestyle interactions on body mass index (BMI). Cross-sectional data from the Japan Multi-Institutional Collaborative Cohort Study were used. Interactions between a multi-locus genetic risk score (GRS), calculated from 76 ancestry-specific single nucleotide polymorphisms, and nutritional intake or physical activity were assessed using a linear mixed-effect model. RESULTS: The mean (standard deviation) BMI and GRS for all participants (n = 12,918) were 22.9 (3.0) kg/m2 and -0.07 (0.16), respectively. The correlation between GRS and BMI was r(12,916) = 0.13 (95% confidence interval [CI] 0.11-0.15, P < 0.001). An interaction between GRS and saturated fatty acid intake was observed (ß = -0.11, 95% CI -0.21 to -0.02). An interaction between GRS and n-3 polyunsaturated fatty acids was also observed in the females with normal-weight subgroup (ß = -0.12, 95% CI -0.22 to -0.03). CONCLUSION: Our results provide evidence of an interaction effect between GRS and nutritional intake and physical activity. This gene-lifestyle interaction provides a basis for developing prevention or treatment interventions for obesity according to individual genetic predisposition.

Association between Dietary Patterns and Serum Low Density Lipoprotein Cholesterol in Japanese Women and Men: The Japan Multi-Institutional Collaborative Cohort (J-MICC) Study.

AIMS: The association between dietary patterns and serum low density lipoprotein (LDL) cholesterol would be changing in recent dietary habits in Japan. We investigated the relationship between dietary patterns and serum LDL cholesterol in a large general population. METHODS: From the baseline survey of Japan Multi-Institutional Collaborative Cohort Study between 2005 and 2013, 27,237 participants (13,994 were women) aged 35-69 years were cross-sectionally analyzed. Using a semi-quantitative food frequency questionnaire, five major sex-specific dietary patterns were identified using factor analysis. We assessed serum LDL cholesterol by quintiles of dietary pattern factor score. RESULTS: We identified dietary patterns; "vegetable rich pattern" , "meat and fried food rich pattern" and "high bread and low rice pattern" in women and men; "fish and shellfish rich pattern" and "high confectioneries and low alcohol pattern" in men; "healthy Japanese diet pattern" and "high alcohol and low rice pattern" in women. Serum LDL cholesterol in men was associated with "high bread and low rice pattern" score (Q5 was 4.2 mg/dL higher than Q1, p for trend ＜0.001) and "high confectioneries and low alcohol pattern" scores (Q5 was 9.5 mg/dL higher than Q1, p for trend ＜0.001). In women, serum LDL cholesterol was associated with "high bread and low rice pattern" score (Q5 was 7.1 mg/dL higher than Q1, p for trend ＜0.001). CONCLUSION: Some recent dietary patterns in Japan were associated with serum LDL cholesterol. Serum LDL cholesterol was associated with high bread and low rice pattern in both sex, and high confectioneries and low alcohol pattern in men.