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Abstract This randomized controlled trial aimed to investigate the effects of eight weeks of lactotripeptide (LTP) ingestion, physical activity (PA) intervention, and combined intervention on the fatigue status of middle-aged and older adults. A total of 78 middle-aged and older adults (63 ± 8 years of age) were randomly assigned to four groups: placebo, LTP, placebo with PA intervention (placebo + PA), and LTP with PA intervention (LTP + PA). All participants ingested the placebo or LTP tablets daily (three tablets/day). The placebo + PA and LTP + PA groups participated in a weekly supervised exercise class and were instructed to increase their moderate- to vigorous-intensity PA at home. The visual analog scale, Brief Fatigue Inventory, Profile of Mood States second edition (POMS2), and Beck Depression Inventory second edition (BDI-II) were administered before and after the intervention. No significant interactions or main effects were observed between LTP ingestion and PA intervention on any of the fatigue scales. The main-effect analyses revealed that the PA intervention improved the total mood disturbance score of the POMS2 (F = 5.22, P = 0.03) and BDI-II score (F = 4.81, P = 0.03). After the post hoc paired comparisons, the total mood disturbance and BDI-II scores improved more with the combined intervention than with the PA intervention alone (percentage difference between the effect of combined intervention and PA intervention alone was 3.7% for total mood disturbance score and 13.7% for BDI-II score). The present study suggests that eight weeks of LTP ingestion and PA intervention did not have a significant effect on fatigue status. However, the PA intervention improved mood status and depressive symptoms, and these effects were enhanced by LTP ingestion.

Abstract Inappropriate activation of intrarenal renin–angiotensin system (RAS) may contribute to the pathogenesis of cardio-renal syndrome (CRS). We aimed to examine the cross-sectional associations of urinary angiotensinogen (AGT) excretion, a biomarker of intrarenal RAS activity, with central (aortic) and renal hemodynamic parameters in middle-aged and older adults, including patients with chronic kidney disease. Aortic and renal hemodynamic parameters were measured using applanation tonometry and duplex ultrasonography in 282 participants. Urinary AGT, liver-type fatty acid-binding protein (L-FABP), and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured for each participant. Multiple linear regression analyses demonstrated that urinary AGT levels were associated with aortic blood pressures, pulsatile measures of renal blood flow, plasma NT-proBNP and urinary L-FABP levels after adjusting for potential covariates, including age, sex, body mass index, estimated glomerular filtration rate (GFR), and medication use. Additionally, when classified based on GFR stages and urinary AGT levels, plasma NT-proBNP and urinary L-FABP levels increased in participants with lower GFR and higher AGT groups. Our findings suggest that urinary AGT excretion is a shared determinant of central (aortic) and renal hemodynamics in middle-aged and older adults, providing clinical evidence for the potential role of intrarenal RAS activity in the development of CRS.

We sought to determine the long-term outcomes of chronic hepatitis B (CHB) cases switching to tenofovir alafenamide (TAF, n = 104, median age = 63.5 years). Data at switching to TAF (baseline) and those at 1, 2, 3, 4, and 5 years from switching to TAF were compared. At baseline, HB envelop antigen (HBeAg) seropositivity was found in 20 patients (19.2%), and undetectable HBV-DNA in 77 patients (74.0%). Percentage of detectable HBV-DNA significantly reduced at any time point. HB surface antigen (HBsAg) levels significantly reduced at 3, 4, and 5 years. The percentage of HBeAg seropositivity significantly reduced at 5 years. HB core related antigen levels did not significantly change. In patients with baseline HbeAg seropositivity, HbsAg levels significantly reduced at any time point, and a similar trend was found in patients without HBeAg seropositivity. In patients with baseline FIB4 index >1.85, HBsAg levels significantly reduced at 3, 4, and 5 years, and in patients with baseline FIB4 index

Age-related loss of lower extremity muscle strength is pronounced in individuals with chronic kidney disease (CKD). In contrast, an increase in intrarenal flow pulsatility results in initial age-related changes in renal hemodynamics, leading to the development of CKD. To date, it remains unclear whether lower extremity muscle strength determines elevated renal flow pulsatility. This study aimed to determine the association of lower extremity muscle strength and function with intrarenal hemodynamics in individuals with and without CKD. One hundred seventy-six individuals without CKD (aged 63 ± 9 years) and 101 individuals with CKD (aged 66 ± 8 years) were included in this study. Using Doppler ultrasound, the renal resistive index (RI) was measured as a parameter of renal hemodynamics. Knee extensor muscle strength (KES), gait speed (GS), and the 30 s chair stand test (30s-CST) were used to measure lower extremity muscle strength and function. Multivariate analyses showed that GS and 30s-CST scores were independent determinants of renal RI, whereas the KES score was not associated with renal RI in individuals with and without CKD. In the two-way analysis of covariance, renal RI was the highest in individuals with CKD who had lower KES, GS, and 30s-CST scores. Reduced lower extremity muscle strength and function are independent determinants of elevated renal flow pulsatility in individuals with and without CKD.

The Prognostic Nutritional Index (PNI) is widely recognized as a screening tool for nutrition. We retrospectively examined the impact of PNI in patients with chronic liver disease (CLD, n = 319, median age = 71 years, 153 hepatocellular carcinoma (HCC) patients) as an observational study. Factors associated with PNI < 40 were also examined. The PNI correlated well with the albumin–bilirubin (ALBI) score and ALBI grade. The 1-year cumulative overall survival rates in patients with PNI ≥ 40 (n = 225) and PNI < 40 (n = 94) were 93.2% and 65.5%, respectively (p < 0.0001). In patients with (p < 0.0001) and without (p < 0.0001) HCC, similar tendencies were found. In the multivariate analysis, hemoglobin (p = 0.00178), the presence of HCC (p = 0.0426), and ALBI score (p < 0.0001) were independent factors linked to PNI < 40. Receiver operating characteristic (ROC) curve analysis based on survival for the PNI yielded an area under the ROC curve of 0.79, with sensitivity of 0.80, specificity of 0.70, and an optimal cutoff point of 42.35. In conclusion, PNI can be a predictor of nutritional status in CLD patients. A PNI of

We sought to investigate the relationship between insulin resistance (IR) and body composition as assessed by bioelectrical impedance analysis in Japanese health check-up recipients (1186 men and 1441 women). IR was defined as a Homeostasis Model Assessment of IR (HOMA-IR) ≥ 2.5. In body-composition-related parameters, the fat mass index (F index) was defined as fat mass divided by the height squared (kg/m2). The fat-free mass index (FF index) was defined as fat-free mass divided by the height squared (kg/m2). The F index to FF index ratio (F-FF ratio) was defined as the F index divided by the FF index. Factors related to HOMA-IR were examined. The median HOMA-IR was 1.54 in men and 1.30 in women (p < 0.0001). The median F index was 4.9 kg/m2 in men and 6.1 kg/m2 in women (p < 0.0001). The median FF index was 18.2 kg/m2 in men and 15.1 kg/m2 in women (p < 0.0001). The median F-FF ratio was 0.272 in men and 0.405 in women (p < 0.0001). The F-FF ratio was an independent factor associated with HOMA-IR in the multivariate analysis in both genders, while the F index and FF index were not in both genders. In conclusion, fat and skeletal muscle balance can be controlled by IR in Japanese adults.

The purpose of this study was to clarify the relationship between the Suita score (a prediction model for the development of cardiovascular disease) and body composition in Japanese health check-up subjects (6873 men and 8685 women). The Suita score includes 8 items (age, gender, smoking, diabetes, blood pressure, low-density lipoprotein, high-density lipoprotein, and chronic kidney disease). Factors associated with the Suita score within body composition-related parameters (body mass index (BMI), waist circumference (WC), fat mass index, fat-free mass index, fat mass to fat-free mass ratio (F-FF ratio), and water mass index) as assessed by bioelectrical impedance analysis were examined. The mean age of subjects was 54.8 years in men and 52.8 years in women (p < 0.0001). The mean BMI was 23.9 kg/m2 in men and 21.8 kg/m2 in women (p < 0.0001). Diabetes mellitus was found in 1282 subjects (18.7%) among men and 816 subjects (9.4%) among women (p < 0.0001). The mean Suita score was 42.0 in men and 29.6 in women (p < 0.0001). In multivariate analysis, WC (p < 0.0001), F-FF ratio (p < 0.0001), and water mass index (p < 0.0001) were independent factors linked to the Suita score for both genders. In conclusion, body composition can be associated with the Suita score in Japanese adults receiving health check-ups.

We sought to examine body composition using bioimpedance analysis in patients with metabolic dysfunction-associated fatty liver disease (MAFLD, 2014 males and 949 females). Factors linked to the fat-free mass index (FF index) were examined using univariate and multivariate analysis. An FF index < 18 kg/m2 in males and an FF index < 15 kg/m2 in females were defined as having decreased skeletal muscle mass. The median age and body mass index (BMI) were 55 years and 25.4 kg/m2 in males, and 57 years and 25.4 kg/m2 in females, respectively. The FF index strongly correlated with muscle mass index both in males (r = 0.999) and females (r = 0.999). The prevalence of patients with an FF index < 18 kg/m2 in males and an FF index < 15 kg/m2 in females was well stratified according to age, BMI, severity of FL, and FIB4 index. In the males, in the multivariate analysis, BMI (p < 0.0001), fat mass index (p < 0.0001), and waist circumference (p = 0.0050) were found to be significant factors linked to FF index. In the females, in the multivariate analysis, BMI (p < 0.0001) and fat mass index (p < 0.0001) were found to be significant. In conclusion, fat accumulation as reflected by BMI, which is an easily available marker, could be a useful indicator for the skeletal muscle mass in MAFLD.

Background: Recent clinical studies have indicated that poor trunk flexibility is associated with arterial stiffness in the aged. Arterial stiffness leads to elevated renal flow pulsatility, which accelerates age-related renal dysfunction and damages. However, data indicating the potential link between flexibility fitness and renal flow pulsatility are lacking. This study examined the cross-sectional association between trunk flexibility and renal flow pulsatility in middle-aged and older adults. Methods: A total of 175 middle-aged and older adults (aged 63 ± 9 years) were included in this study. Sit-and-reach tests (SRT) were performed to assess their trunk flexibility. Using a Doppler ultrasound, renal pulsatility index (PI) and resistive index (RI) were measured as parameters of renal flow pulsatility. Results: The study found that, in middle-aged and older adults, the SRT score was an independent determinant of renal PI (β = −0.134, P = 0.027) and RI (β = −0.135, P = 0.027). In the one-way analysis of covariance (ANCOVA), the renal PI and RI in the older group with a lower SRT score were found to be significantly higher than those in the middle-aged group. Conclusions: Trunk flexibility is an independent determinant of renal flow pulsatility in middle-aged and older adults.

SARC-F is a well-accepted screening tool for sarcopenia. A SARC-F value of 1 point is reported to be more discriminating in identifying sarcopenia than 4 points (recommended cutoff point). The prognostic impact of the SARC-F score was investigated in patients with liver disease (LD, n = 269, median age = 71 years, 96 hepatocellular carcinoma (HCC) cases). Factors associated with SARC-F ≥ 4 points and SARC-F ≥ 1 point were also examined. In the multivariate analysis, age (p = 0.048), and Geriatric Nutritional Risk Index (GNRI) score (p = 0.0365) were significant factors linked to SARC-F ≥ 1 point. In our patients with LD, the SARC-F score is well correlated with the GNRI score. The 1-year cumulative overall survival ratio in patients with SARC-F ≥ 1 (n = 159) and SARC-F 0 (n = 110) was 78.3% and 90.1% (p = 0.0181). After excluding 96 HCC cases, similar tendencies were found (p = 0.0289). In the receiver operating curve (ROC) analysis based on the prognosis for the SARC-F score, the area under the ROC was 0.60. The sensitivity was 0.57, the specificity was 0.62, and the optimal cutoff point of the SARC-F score was 1. In conclusion, sarcopenia in LDs can be affected by nutritional conditions. A SARC-F score of ≥1 is more useful than a score of 4 in predicting the prognosis of patients with LD.

Abstract Background Physical inactivity and sedentary behaviour (too much sitting) can contribute to renal dysfunction. However, the potential benefits of behavioural change (e.g. replacing sedentary behaviour with physical activity) on renal function are not well understood. We used isotemporal substitution to model potential impacts of behaviours on renal function by replacing time spent in one behaviour to another. Methods In 174 older Japanese adults (age, 50–83 years; females, 76%), the time spent in sedentary behaviour, light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA) were assessed using an uniaxial accelerometer. Renal function was evaluated by the estimated glomerular filtration rate (eGFR) from serum creatinine and cystatin C levels. Results In univariate analyses, eGFR was significantly, albeit weakly, correlated with time spent in sedentary behaviour (r s = − 0.229), LPA (r s = 0.265), and MVPA (r s = 0.353). In the isotemporal substitution models, replacement of 30 min/day of sedentary behaviour with an equivalent LPA time was not significantly associated with eGFR (β = 2.26, p = 0.112); however, replacement with an equivalent time of MVPA was beneficially associated with eGFR (β = 5.49, p

This study aims to evaluate the association between duration of overweight/obesity and arterial stiffness. In total, 103 men and women aged 45–68 years with a body mass index (BMI) of ≥25 kg/m2 were enrolled in this study. Duration of overweight/obesity was calculated for individuals with at least two consecutive BMI occurrences of ≥25 kg/m2 in the previous (5-year intervals from 20 years old) and present BMI information. Multiple regression analysis showed that carotid-femoral pulse wave velocity, an index of arterial stiffness, was independently associated with the duration of overweight/obesity, but not with current degree of overweight/obesity.

ABSTRACT Nonalcoholic fatty liver disease (NAFLD), characterized by excessive fat deposition in the liver unrelated to alcohol consumption, is highly prevalent worldwide. However, effective therapeutic agents approved for NAFLD treatment are lacking. An ileal bile acid transporter inhibitor (IBATi), which represents a new mode of treatment of chronic idiopathic constipation, leads to increased delivery of bile acids to the colon. We investigated the effect of IBATi against NAFLD through modification of the gut microbiota in mice. IBATi treatment significantly suppressed body weight gain, liver dysfunction, and serum low-density lipoprotein levels and significantly decreased NAFLD activity scores in high-fat diet (HFD) mice. Treatment with IBATi ameliorated the decreased hepatic cholesterol 7-a-monooxygenase (Cyp7a1) and increased ileal fibroblast growth factor 15 (Fgf15) mRNA expression in HFD mice. Further, IBATi treatment changed the α-diversity in the gut microbiota reduced by HFD, which was analyzed in feces using 16S rRNA sequencing. To establish the mechanism underlying improvement in NAFLD induced by IBATi, we recolonized antibiotic solution-treated mice by fecal microbiome transplantation (FMT) using stool from HFD or HFD plus IBATi mice. This is the first report that fecally transplanted gut microbiota from HFD plus IBATi mice prevented hepatic steatosis caused by HFD. In conclusion, IBATi improved hepatic steatosis by ameliorating gut microbiota dysbiosis in NAFLD model mice, suggesting a potential therapeutic agent for NAFLD treatment. IMPORTANCE NAFLD is an increasingly recognized condition that may progress to liver cirrhosis and hepatocellular carcinoma, and community surveys have assessed that the prevalence is 14 to 32% worldwide. The first line of treatment for NAFLD is lifestyle modification to achieve weight reduction, particularly through diet and exercise. However, weight reduction is difficult to achieve and maintain, and pharmacological agents approved for the treatment of NAFLD are lacking. This study investigated the influence of the gut microbiota and the effect of an IBATi on NAFLD using a murine model. Treatment with IBATi significantly improved NAFLD in HFD mice. Further, fecal microbiome transplantation using stool from HFD plus IBATi mice prevented hepatic steatosis caused by HFD. Our study makes a significant contribution to the literature because the study findings suggest a potential treatment strategy for NAFLD patients by ameliorating gut microbiota dysbiosis.

Circulating fibroblast growth factor-21 (FGF21) has been reported to correlate with development and progression of some chronic diseases including diabetes and obesity. However, the association between circulating FGF21 levels, aerobic fitness, and aortic blood pressure (BP) is still not fully understood. This study aimed to examine potential association between circulating FGF21 levels, aerobic fitness, and aortic BP in 118 middle-aged and older women. Aortic pulse pressure (PP) in the higher FGF21 group was significantly increased when compared to the lower FGF21 group (38.4 ± 1.1 vs. 34.9 ± 0.8 mmHg; P < 0.05). Multivariate analysis found the circulating FGF21 level to be an independent determinant of aortic PP (β = 0.169; P < 0.05); and this finding was also independently determined by VO2peak (β = −0.235; P < 0.01). Such a finding demonstrated that serum FGF21 levels were associated positively with aortic PP and negatively with aerobic fitness. These results have raised the possibility that FGF21 might contribute to an increase in aortic PP, and that the promotion of aerobic fitness might be effective in maintaining low FGF21 levels in middle-aged and older women.

Exposure of a building to a tornado often proves fatal, resulting in massive destruction of property and structures. The effect of disasters can be minimized by understanding the nature of fluid-structure interactions when a tornado hits a building on its path. Earlier researchers have investigated extensively on building models exposed to stationary type vortex generated in a laboratory type tornado simulator; however studies using translating type vortex are few. In the present investigation, the external and internal pressures experienced by a building model are discussed based on experiments conducted using a translating tornado-like flow simulator at Tokyo Polytechnic University, Japan. The swirl ratio which characterizes the strength of vortices generated is kept constant. The investigation attempts to explore the opening locations which can result in higher internal pressures and net roof forces in building and the vulnerability of roof structures of buildings when exposed to tornado-like flow. The effect of translating speed on internal pressure fluctuations when compared to those of external pressures are investigated using aerodynamic admittance functions. Results indicate that there is an increased amount of internal pressure fluctuations at higher translating speeds.

The World Health Organization has recommended 5 g/day as dietary reference intakes for salt. In Japan, the averages for men and women were 11.0 g/day and 9.3 g/day, respectively. Recently, it was reported that amounts of sodium accumulation in skeletal muscles of older people were significantly higher than those in younger people. The purpose of this study was to investigate whether the risk of sarcopenia with decreased muscle mass and strength was related to the amount of salt intake. In addition, we investigated its involvement with renalase. Four groups based on age and salt intake (“younger low-salt,” “younger high-salt,” “older low-salt,” and “older high-salt”) were compared. Stratifying by age category, body fat percentage significantly increased in high-salt groups in both younger and older people. Handgrip strength/body weight and chair rise tests of the older high-salt group showed significant reduction compared to the older low-salt group. However, there was no significant difference in renalase concentrations in plasma. The results suggest that high-salt intake may lead to fat accumulation and muscle weakness associated with sarcopenia. Therefore, efforts to reduce salt intake may prevent sarcopenia.

Background/Aim: To examine the relationship between the body surface area (BSA) and body composition in patients with metabolic dysfunction-associated steatotic liver disease (MASLD, 2,141 men and 986 women). Materials and Methods: BSA and body composition parameters were examined. Results: The median body mass index (BMI) was 25.0 kg/m² for both men and women (p=0.7754). The median body surface area (BSA) was 1.854 m² for men and 1.618 m² for women (p<0.0001). In men, the median fat mass was 17.7 kg, whereas in women, it was 22.1 kg (p<0.0001). Additionally, the median fat-free mass was 55.4 kg in men and 39.3 kg in women (p<0.0001).). In male cases, BSA significantly correlated with fat mass (r=0.82, p<0.0001) and fat-free mass (r=0.95, p<0.0001). In female cases, BSA significantly correlated with fat mass (r=0.87, p<0.0001) and fat-free mass (r=0.94, p<0.0001). Conclusion: BSA could be a useful marker for the estimation of body composition in patients with MASLD. [ABSTRACT FROM AUTHOR]