Short- and long-term performance of risk calculation tools for mortality in patients with acute coronary syndrome.

Background: The mortality rate of acute coronary syndrome (ACS) remains high. Therefore, patients with ACS should undergo early risk stratification, for which various risk calculation tools are available. However, it remains uncertain whether the predictive performance varies over time between risk calculation tools for different target periods. This study aimed to compare the predictive performance of risk calculation tools in estimating short- and long-term mortality risks in patients with ACS, while considering different observation periods using time-dependent receiver operating characteristic (ROC) analysis. Methods: This study included 404 consecutive patients with ACS who underwent coronary angiography at our hospital from March 2017 to January 2021. The ACTION and GRACE scores for short-term risk stratification purposes and CRUSADE scores for long-term risk stratification purposes were calculated for all participants. The participants were followed up for 36 months to assess mortality. Using time-dependent ROC analysis, we evaluated the area under the curve (AUC) of the ACTION, CRUSADE, and GRACE scores at 1, 6, 12, 24, and 36 months. Results: Sixty-six patients died during the observation periods. The AUCs at 1, 6, 12, 24, and 36 months of the ACTION score were 0.942, 0.925, 0.889, 0.856, and 0.832; those of the CRUSADE score were 0.881, 0.883, 0.862, 0.876, and 0.862; and those of the GRACE score 0.949, 0.928, 0.888, 0.875, and 0.860, respectively. Conclusions: The ACTION and GRACE scores were excellent risk stratification tools for mortality in the short term. The prognostic performance of each risk score was almost similar in the long term, but the CRUSADE score might be a superior risk stratification tool in the longer term than 3 years.

Dietary salt intake predicts future development of metabolic syndrome in the general population.

Excessive dietary salt consumption is one of the most important risk factors for hypertension. Metabolic disorders often coexist with hypertension, and excess salt intake has been reported to underlie metabolic disorders, such as insulin resistance. Therefore, we tested the hypothesis that excessive dietary salt causes metabolic syndrome in the general population. In total, 13886 subjects who participated in our medical checkup were enrolled, and salt intake was assessed using a spot urine sample. The characteristics of participants with metabolic syndrome (n = 1630) were examined at baseline, and then participants without metabolic syndrome (n = 12256) were followed up with the endpoint being the development of metabolic syndrome. The average estimated salt intake in our participants was 8.72 ± 1.93 g/day. A significant association between salt intake and metabolic syndrome was obtained from the logistic regression analysis, and salt intake increased as the number of metabolic disorders in an individual increased at baseline (P < 0.001). During the median follow-up period of 52 months, 1669 participants developed metabolic syndrome. Kaplan-Meier analysis demonstrated an increased risk of metabolic syndrome across quartiles of baseline salt intake (log-rank, P < 0.001). In the Cox proportional hazard regression analysis where salt intake was taken as a continuous variable, salt intake at baseline was an independent predictor of developing metabolic syndrome. These results suggest that excessive salt intake is significantly associated with the development of metabolic syndrome in the general population. Salt may play an important role in the development of metabolic disorders and hypertension.

Blood pressure variability and the development of hypertensive organ damage in the general population.

Increasing blood pressure variability (BPV) has been reported to be a strong predictor of cardiovascular events in patients with hypertension. However, the effects of BPV in the general population have not been intensively studied. The present study was designed to investigate a possible relationship between year-to-year BPV and hypertensive target organ damage (TOD) in a relatively low-risk general population. A total of 5489 consecutive patients (mean age 58.6 ± 10.7 years) who visited our hospital for an annual physical checkup for five consecutive years during 2008-2013 were enrolled in this study. The average systolic and diastolic blood pressures and pulse pressure were calculated, as well as standard deviation, coefficient of variation, and average real variability in blood pressures. Cross-sectional analysis was conducted and subjects without TOD at baseline (n = 3115) were followed up (median 1827 days) with the endpoint of TOD, defined as left ventricular hypertrophy on electrocardiogram or declining glomerular filtration rate. At baseline, BPV was closely associated with TOD. During follow-up, left ventricular hypertrophy and declining glomerular filtration rate developed in 189 and 400 subjects, respectively. Although the standard deviation for systolic blood pressure and pulse pressure predicted future development of TOD in a univariate analysis, BPV was not a significant determinant of incident TOD in adjusted Cox hazard models. These results suggest that year-to-year BPV is a marker of the presence of TOD in the general population but does not independently predict future TOD.

Effects of Nutrient Intake Timing on Post-Exercise Glycogen Accumulation and its Related Signaling Pathways in Mouse Skeletal Muscle.

We investigated the effects of nutrient intake timing on glycogen accumulation and its related signals in skeletal muscle after an exercise that did not induce large glycogen depletion. Male ICR mice ran on a treadmill at 25 m/min for 60 min under a fed condition. Mice were orally administered a solution containing 1.2 mg/g carbohydrate and 0.4 mg/g protein or water either immediately (early nutrient, EN) or 180 min (late nutrient, LN) after the exercise. Tissues were harvested at 30 min after the oral administration. No significant difference in blood glucose or plasma insulin concentrations was found between the EN and LN groups. The plantaris muscle glycogen concentration was significantly (p < 0.05) higher in the EN group-but not in the LN group-compared to the respective time-matched control group. Akt Ser473 phosphorylation was significantly higher in the EN group than in the time-matched control group (p < 0.01), while LN had no effect. Positive main effects of time were found for the phosphorylations in Akt substrate of 160 kDa (AS160) Thr642 (p < 0.05), 5'-AMP-activated protein kinase (AMPK) Thr172 (p < 0.01), and acetyl-CoA carboxylase Ser79 (p < 0.01); however, no effect of nutrient intake was found for these. We showed that delayed nutrient intake could not increase muscle glycogen after endurance exercise which did not induce large glycogen depletion. The results also suggest that post-exercise muscle glycogen accumulation after nutrient intake might be partly influenced by Akt activation. Meanwhile, increased AS160 and AMPK activation by post-exercise fasting might not lead to glycogen accumulation.

Effects of ß-hydroxybutyrate treatment on glycogen repletion and its related signaling cascades in epitrochlearis muscle during 120 min of postexercise recovery.

We investigated the effects of ß-hydroxybutyrate (ß-HB), the most abundant type of ketone body in mammals, on postexercise glycogen recovery in skeletal muscle by using an in vitro experimental model. Male ICR mice swam for 60 min and then their epitrochlearis muscles were removed and incubated with either physiological levels of glucose (8 mmol/L) and insulin (60 µU/mL) or glucose and insulin plus 1, 2, or 4 mmol/L of sodium ß-HB. Four millimoles per liter ß-HB had a significant positive effect on glycogen repletion in epitrochlearis muscle at 120 min after exercise (p < 0.01), while 2 mmol/L of ß-HB showed a tendency to increase the glycogen level (p < 0.09), and 1 mmol/L of ß-HB had no significant effect. We further investigated the effect of 4 mmol/L ß-HB treatment on the signaling cascade related to glycogen repletion in the epitrochlearis muscles throughout a 120-min recovery period. After incubating the muscles in 4 mmol/L of ß-HB for 15 min postexercise, the Akt substrate of 160 kDa Thr642 (p < 0.05) and Akt Thr308 (p < 0.05) phosphorylations were significantly increased compared with the control treatment. At the same time point, 5'-AMP-activated protein kinase and acetyl-coenzyme A carboxylase phosphorylations were significantly lower (p < 0.05) in the epitrochlearis muscle incubated with 4 mmol/L of ß-HB than in the control muscle. Our results demonstrate that postexercise 4 mmol/L ß-HB administration enhanced glycogen repletion in epitrochlearis muscle. Four millimoles per liter ß-HB treatment was associated with alternation of the phosphorylated status of several proteins involved in glucose uptake and metabolic/energy homeostasis at the early stage of postexercise.

Effects of Royal Jelly Administration on Endurance Training-Induced Mitochondrial Adaptations in Skeletal Muscle.

We investigated the effect of royal jelly (RJ), a natural secretion from worker bees, on the endurance training-induced mitochondrial adaptations in skeletal muscles of ICR mice. Mice received either RJ (1.0 mg/g body weight) or distilled water for three weeks. The mice in the training group were subjected to endurance training (20 m/min; 60 min; 5 times/week). There was a main effect of endurance training on the maximal activities of the mitochondrial enzymes, citrate synthase (CS), and ß-hydroxyacyl coenzyme Adehydrogenase (ß-HAD), in the plantaris and tibialis anterior (TA) muscles, while no effect of RJ treatment was observed. In the soleus muscle, CS and ß-HAD maximal activities were significantly increased by endurance training in the RJ-treated group, while there was no effect of training in the control group. Furthermore, we investigated the effects of acute RJ treatment on the signaling cascade involved in mitochondrial biogenesis. In the soleus, phosphorylation of 5'-AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) were additively increased by a single RJ treatment and endurance exercise, while only an exercise effect was found in the plantaris and TA muscles. These results indicate that the RJ treatment induced mitochondrial adaptation with endurance training by AMPK activation in the soleus muscles of ICR mice.

Netrin-5 is highly expressed in neurogenic regions of the adult brain.

Mammalian netrin family proteins are involved in targeting of axons, neuronal migration, and angiogenesis and act as repulsive and attractive guidance molecules. Netrin-5 is a new member of the netrin family with homology to the C345C domain of netrin-1. Unlike other netrin proteins, murine netrin-5 consists of two EGF motifs of the laminin V domain (LE) and the C345C domain, but lacks the N-terminal laminin VI domain and one of the three LE motifs. We generated a specific antibody against netrin-5 to investigate its expression pattern in the rodent adult brain. Strong netrin-5 expression was observed in the olfactory bulb (OB), rostral migrate stream (RMS), the subventricular zone (SVZ), and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus, where neurogenesis occurs in the adult brain. In the SVZ and RMS, netrin-5 expression was observed in Mash1-positive transit-amplifying cells and in Doublecortin (DCX)-positive neuroblasts, but not in GFAP-positive astrocytes. In the OB, netrin-5 expression was maintained in neuroblasts, but its level was decreased in NeuN-positive mature neurons. In the hippocampal SGZ, netrin-5 was observed in Mash1-positive cells and in DCX-positive neuroblasts, but not in GFAP-positive astrocytes, suggesting that netrin-5 expression occurs from type 2a to type 3 cells. These data suggest that netrin-5 is produced by both transit-amplifying cells and neuroblasts to control neurogenesis in the adult brain.

Fabrication of novel multilayered thin films based on inclusion complex formation between amylose derivatives and guest polymers.

Novel types of layer-by-layer (LbL) assembly films were successfully fabricated onto a solid substrate through the inclusion complex formation between partially 2,3- O-methylated amyloses (MAs) and polytetrahydrofuran (PTHF). The formation of the LbL assembly films was confirmed by quartz crystal microbalance (QCM) analysis, atomic force microscopy (AFM) observation, and X-ray diffraction (XRD) measurement. The film formation was significantly affected by the methylation degree of amylose. When MAs with 8 and 20% methylation were used as hosts, the formation of LbL assembly films with PTHF was clearly observed. On the other hand, MAs with more than 33% methylation barely formed LbL assembly films with PTHF.