Angelica gigas extract inhibits acetylation of eNOS via IRE1α sulfonation/RIDD-SIRT1-mediated posttranslational modification in vascular dysfunction.

Angelica gigas NAKAI (AG) is a popular traditional medicinal herb widely used to treat dyslipidemia owing to its antioxidant activity. Vascular disease is intimately linked to obesity-induced metabolic syndrome, and AG extract (AGE) shows beneficial effects on obesity-associated vascular dysfunction. However, the effectiveness of AGE against obesity and its underlying mechanisms have not yet been extensively investigated. In this study, 40 high fat diet (HFD) rats were supplemented with 100-300 mg/kg/day of AGE to determine its efficacy in regulating vascular dysfunction. The vascular relaxation responses to acetylcholine were impaired in HFD rats, while the administration of AGE restored the diminished relaxation pattern. Endothelial dysfunction, including increased plaque area, accumulated reactive oxygen species, and decreased nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) Ser1177 phosphorylation, were observed in HFD rats, whereas AGE reversed endothelial dysfunction and its associated biochemical signaling. Furthermore, AGE regulated endoplasmic reticulum (ER) stress and IRE1α sulfonation and its subsequent sirt1 RNA decay through controlling regulated IRE1α-dependent decay (RIDD) signaling, ultimately promoting NO bioavailability via the SIRT1-eNOS axis in aorta and endothelial cells. Independently, AGE enhanced AMPK phosphorylation, additionally stimulating SIRT1 and eNOS deacetylation and its associated NO bioavailability. Decursin, a prominent constituent of AGE, exhibited a similar effect in alleviating endothelial dysfunctions. These data suggest that AGE regulates dyslipidemia-associated vascular dysfunction by controlling ROS-associated ER stress responses, especially IRE1α-RIDD/sirt1 decay and the AMPK-SIRT1 axis.

Efficacy and Safety of Sesame Oil Cake Extract on Memory Function Improvement: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Pilot Study.

The goal of treatment for mild cognitive impairment (MCI) is to reduce the existing clinical symptoms, delay the progression of cognitive impairment and prevent the progression to Alzheimer's disease (AD). At present, there is no effective drug therapy for AD treatment. However, early intake of dietary supplements may be effective in alleviating and delaying the MCI. This study aims to evaluate the effects of sesame oil cake extract (SOCE) supplementation on cognitive function in aged 60 years or older adults with memory impairment. A total of 70 subjects received either SOCE (n = 35) or placebo (n = 35) for 12 weeks based on random 1:1 assignment to these two groups. Cognitive function was evaluated by a computerized neurocognitive function test (CNT), and changes in the concentrations of plasma amyloid ß (Aß) proteins and urine 8-OHdG (8-hydroxy-2'-deoxyguanosine) were investigated before and after the experiment. Verbal learning test index items of the CNT improved markedly in the SOCE group compared to the placebo group (p < 0.05). Furthermore, plasma amyloid-ß (1-40) and amyloid-ß (1-42) levels in the SOCE group decreased significantly compared to that in the placebo group (p < 0.05). There was no statistically significant difference in urine 8-OHdG between the two groups (p > 0.05). Collectively, intake of SOCE for 12 weeks appears to have a beneficial effect on the verbal memory abilities and plasma ß-amyloid levels of older adults with memory impairment.

Anthocyanins attenuate endothelial dysfunction through regulation of uncoupling of nitric oxide synthase in aged rats.

Endothelial dysfunction is one of the main age-related arterial phenotypes responsible for cardiovascular disease (CVD) in older adults. This endothelial dysfunction results from decreased bioavailability of nitric oxide (NO) arising downstream of endothelial oxidative stress. In this study, we investigated the protective effect of anthocyanins and the underlying mechanism in rat thoracic aorta and human vascular endothelial cells in aging models. In vitro, cyanidin-3-rutinoside (C-3-R) and cyanidin-3-glucoside (C-3-G) inhibited the d-galactose (d-gal)-induced senescence in human endothelial cells, as indicated by reduced senescence-associated-ß-galactosidase activity, p21, and p16INK4a . Anthocyanins blocked d-gal-induced reactive oxygen species (ROS) formation and NADPH oxidase activity. Anthocyanins reversed d-gal-mediated inhibition of endothelial nitric oxide synthase (eNOS) serine phosphorylation and SIRT1 expression, recovering NO level in endothelial cells. Also, SIRT1-mediated eNOS deacetylation was shown to be involved in anthocyanin-enhanced eNOS activity. In vivo, anthocyanin-rich mulberry extract was administered to aging rats for 8 weeks. In vivo, mulberry extract alleviated endothelial senescence and oxidative stress in the aorta of aging rats. Consistently, mulberry extract also raised serum NO levels, increased phosphorylation of eNOS, increased SIRT1 expression, and reduced nitrotyrosine in aortas. The eNOS acetylation was higher in the aging group and was restored by mulberry extract treatment. Similarly, SIRT1 level associated with eNOS decreased in the aging group and was restored in aging plus mulberry group. These findings indicate that anthocyanins protect against endothelial senescence through enhanced NO bioavailability by regulating ROS formation and reducing eNOS uncoupling.

Effects of a Lifestyle-Modification Program on Blood-Glucose Regulation and Health Promotion in Diabetic Patients: A Randomized Controlled Trial.

BACKGROUND: We aimed to investigate the efficacy of the lifestyle intervention (LSI) program in controlling blood glucose regulation and health promotion in type 2 diabetic (T2D) patients. METHODS: Thirty adults with a diagnosed with diabetes were randomly assigned to LSI and control groups. The LSI group maintained their daily routines after participating twice in the LSI program, while control group maintained 4 weeks of daily life without participating in an intervention. RESULTS: HbA1c levels in the LSI group decreased significantly after participation (p = 0.025) compared with levels before the study, but there was no significant difference between the groups. The weight and body mass index (BMI) of the LSI group tended to decrease significantly compared with the control group (p = 0.054 and p = 0.055, respectively), and the waist circumference (WC) of the LSI group decreased significantly compared with that of the control group (p = 0.048). In the effects of the LSI program according to the polymorphism of GCKR genes, changes in glycated albumin (GA) (%), HbA1c, WC, BMI, and weight showed a significant decrease in the non-risk (TT genotype) GCKR group compared with the risk group (CC and TC genotype). CONCLUSION: Application of the four-week LSI program to diabetics revealed positive effects on blood-glucose control and improvement in obesity indicators. In particular, the risk group with variations in the GCKR gene was associated with more genetic effects on indicators such as blood glucose and obesity than was the non-risk group.

Effects of Porphyra tenera Supplementation on the Immune System: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial.

OBJECTIVE: The purpose of this study was to determine if Porphyra tenera extract (PTE) has immune-enhancing effects and is safe in healthy adults. METHODS: Subjects who met the inclusion criteria (3 × 103 ≤ peripheral blood leukocyte level ≥ 8 × 103 cells/µL) were recruited for this study. Enrolled subjects (n = 120) were randomly assigned to either the PTE group (n = 60) and were given 2.5 g/day of PTE (as PTE) in capsule form or the placebo group (n = 60) and were given crystal cellulose capsules with the identical appearance, weight, and flavor as the PTE capsules for 8 weeks. Outcomes were assessed based on measuring natural killer (NK) cell activity, cytokines level, and upper respiratory infection (URI), and safety parameters were assessed at baseline and 8 weeks. RESULTS: Compared with baseline, NK cell activity (%) increased for all effector cell-to-target cell ratios in the PTE group after 8 weeks; however, changes were not observed in the placebo group (p < 0.10). Subgroup analysis of 101 subjects without URI showed that NK cell activity in the PTE group tended to increase for all effector cell/target cell (E:T) ratios (E:T = 12.5:1 p = 0.068; E:T = 25:1 p = 0.036; E:T = 50:1 p = 0.081) compared with the placebo group. A significant difference between the two groups was observed for the E:T = 25:1 ratio, which increased from 20.3 ± 12.0% at baseline to 23.2 ± 12.4% after 8 weeks in the PTE group (p = 0.036). A significant difference was not observed in cytokine between the two groups. CONCLUSION: PTE supplementation appears to enhance immune function by improving NK cell activity without adverse effects in healthy adults.

The Validity of the YMCA 3-Minute Step Test for Estimating Maximal Oxygen Uptake in Healthy Korean and Vietnamese Adults.

BACKGROUND: Cardiorespiratory fitness (CRF) is a fundamental component of physical fitness. While maximal oxygen uptake (VO2max) is the gold standard for quantifying CRF, standard maximal exercise tests using direct measurements VO2max are dependent on the availability of laboratory equipment, and thereby expensive and time consuming. Recently, an equation was formulated to indirectly estimate VO2max using the YMCA 3-minute step test. METHODS: The study included 15 Korean (KR) and 15 Vietnamese (VN) healthy adults aged 19-35 years. All subjects completed a YMCA 3-minute step test (YMCA 3MST) and a maximal exercise treadmill test to predict VO2max and VO2max measures, respectively. RESULTS: There was a significant relationship between VO2max predicted from the YMCA 3MST and actual VO2max measurements from the treadmill test (r = 0.80, p < 0.0001; KR group: r = 0.81, p < 0.0001; VN group: r = 0.93, p < 0.0001). Bland-Altman analysis revealed statistical agreement between tests, although there was a systematic overestimation of 3.36 mL/kg/min for the KR group. CONCLUSION: The equation for predicting VO2max from the YMCA 3MST was validated among the study subjects. However, future research should explore the validity and reliability of the YMCA 3MST equation for estimating VO2max in other populations.

Serum Follicle-Stimulating Hormone Levels Are Associated with Cardiometabolic Risk Factors in Post-Menopausal Korean Women.

: Menopause compounds many cardiometabolic risk factors through endogenous estrogen withdrawal. This study aimed to find the association between serum follicle-stimulating hormone (FSH) levels and cardiometabolic risk factors in post-menopausal Korean women. A total of 608 post-menopausal women from eight randomized double-blind, placebo-controlled clinical trials on menopause during the year 2012-2019 were analyzed. Cardiometabolic risk factors such as body mass index, waist circumference, systolic blood pressure, fasting glucose, triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), and TG/HDL-C ratio were significantly improved as the FSH quartiles increased. Metabolic syndrome (MetS) and the number of components of MetS decreased as FSH quartiles increased. In regression analysis, FSH level was negatively associated with cardiometabolic risk factors including body mass index, body weight, waist circumference, fasting glucose and TG, while it was positively associated with HDL-C. The odds ratio of MetS in the first quartile of FSH was 2.682 compared with that in the fourth quartile of FSH in a logistic regression model. Serum FSH levels had a negative correlation with cardiometabolic risk factors in post-menopausal Korean women, suggesting that a low FSH can be a predictor for cardiovascular disease in post-menopausal women.

A Lightweight Deep Learning Model for Fast Electrocardiographic Beats Classification With a Wearable Cardiac Monitor: Development and Validation Study.

BACKGROUND: Electrocardiographic (ECG) monitors have been widely used for diagnosing cardiac arrhythmias for decades. However, accurate analysis of ECG signals is difficult and time-consuming work because large amounts of beats need to be inspected. In order to enhance ECG beat classification, machine learning and deep learning methods have been studied. However, existing studies have limitations in model rigidity, model complexity, and inference speed. OBJECTIVE: To classify ECG beats effectively and efficiently, we propose a baseline model with recurrent neural networks (RNNs). Furthermore, we also propose a lightweight model with fused RNN for speeding up the prediction time on central processing units (CPUs). METHODS: We used 48 ECGs from the MIT-BIH (Massachusetts Institute of Technology-Beth Israel Hospital) Arrhythmia Database, and 76 ECGs were collected with S-Patch devices developed by Samsung SDS. We developed both baseline and lightweight models on the MXNet framework. We trained both models on graphics processing units and measured both models' inference times on CPUs. RESULTS: Our models achieved overall beat classification accuracies of 99.72% for the baseline model with RNN and 99.80% for the lightweight model with fused RNN. Moreover, our lightweight model reduced the inference time on CPUs without any loss of accuracy. The inference time for the lightweight model for 24-hour ECGs was 3 minutes, which is 5 times faster than the baseline model. CONCLUSIONS: Both our baseline and lightweight models achieved cardiologist-level accuracies. Furthermore, our lightweight model is competitive on CPU-based wearable hardware.

Biosignal-Based Attention Monitoring to Support Nuclear Operator Safety-Relevant Tasks.

In the main control room (MCR) of a nuclear power plant (NPP), the quality of an operator's performance can depend on their level of attention to the task. Insufficient operator attention accounted for more than 26% of the total causes of human errors and is the highest category for errors. It is therefore necessary to check whether operators are sufficiently attentive either as supervisors or peers during reactor operation. Recently, digital control technologies have been introduced to the operating environment of an NPP MCR. These upgrades are expected to enhance plant and operator performance. At the same time, because personal computers are used in the advanced MCR, the operators perform more cognitive works than physical work. However, operators may not consciously check fellow operators' attention in this environment indicating potentially higher importance of the role of operator attention. Therefore, remote measurement of an operator's attention in real time would be a useful tool, providing feedback to supervisors. The objective of this study is to investigate the development of quantitative indicators that can identify an operator's attention, to diagnose or detect a lack of operator attention thus preventing potential human errors in advanced MCRs. To establish a robust baseline of operator attention, this study used two of the widely used biosignals: electroencephalography (EEG) and eye movement. We designed an experiment to collect EEG and eye movements of the subjects who were monitoring and diagnosing nuclear operator safety-relevant tasks. There was a statistically significant difference between biosignals with and without appropriate attention. Furthermore, an average classification accuracy of about 90% was obtained by the k-nearest neighbors and support vector machine classifiers with a few EEG and eye movements features. Potential applications of EEG and eye movement measures in monitoring and diagnosis tasks in an NPP MCR are also discussed.

Neural Correlates of Variations in Human Trust in Human-like Machines during Non-reciprocal Interactions.

As intelligent machines have become widespread in various applications, it has become increasingly important to operate them efficiently. Monitoring human operators' trust is required for productive interactions between humans and machines. However, neurocognitive understanding of human trust in machines is limited. In this study, we analysed human behaviours and electroencephalograms (EEGs) obtained during non-reciprocal human-machine interactions. Human subjects supervised their partner agents by monitoring and intervening in the agents' actions in this non-reciprocal interaction, which reflected practical uses of autonomous or smart systems. Furthermore, we diversified the agents with external and internal human-like factors to understand the influence of anthropomorphism of machine agents. Agents' internal human-likenesses were manifested in the way they conducted a task and affected subjects' trust levels. From EEG analysis, we could define brain responses correlated with increase and decrease of trust. The effects of trust variations on brain responses were more pronounced with agents who were externally closer to humans and who elicited greater trust from the subjects. This research provides a theoretical basis for modelling human neural activities indicate trust in partner machines and can thereby contribute to the design of machines to promote efficient interactions with humans.

Mulberry Extract Attenuates Endothelial Dysfunction through the Regulation of Uncoupling Endothelial Nitric Oxide Synthase in High Fat Diet Rats.

Dyslipidemia is associated with endothelial dysfunction, which is linked to nitric oxide (NO) biology. The coupling of endothelial NO synthase with cofactors is a major step for NO release. This study is aimed to investigate the vascular pharmacology effects of mulberry in rat thoracic aorta and human vascular endothelial cells. In vitro, we investigated the protective effects of the mulberry extract and its main component cyanidin-3-rutinoside (C-3-R), against oxidized low-density lipoprotein (ox-LDL)-induced endothelial nitric oxide synthase (eNOS) uncoupling. Whereas ox-LDL significantly decreased NO levels in endothelial cells, mulberry extract, and C-3-R significantly recovered NO levels and phospho-eNOS Thr495 and Ser1177 expression. In vivo, mulberry was administered to 60% of high-fat diet (w/w)-fed Sprague Dawley (SD) rats for six weeks, in which endothelium-dependent relaxations were significantly improved in organ bath studies and isometric tension recordings. Consistently, aortic expressions of phospho-eNOS and nitrotyrosine were increased. Mulberry also raised serum NO levels, increased phosphorylation of eNOS, and reduced nitrotyrosine and intracellular reactive oxygen species (ROS) in aortas, showing that mulberry preserves endothelium-dependent relaxation in aortas from high-fat diet rats. We suggest that this effect is mediated through enhanced NO bioavailability, in which the regulation of ROS and its reduced eNOS uncoupling are involved.

Immunomodulatory effects of a mycelium extract of Cordyceps (Paecilomyces hepiali; CBG-CS-2): a randomized and double-blind clinical trial.

BACKGROUND: Cordyceps is a traditional Chinese herb that produces various biopharmaceutical effects, including immune-enhancing effects. In this study, we prepared a Cordyceps mycelium culture extract (Paecilomyces hepiali, CBG-CS-2) to confirm its efficacy in enhancing the immune system and to evaluate its safety in healthy adults. METHODS: Healthy adults were divided into the intervention group (n = 39), who were given 1.68 g/day of CBG-CS-2 in capsules, and the control group (n = 40) for 8 weeks. The activities of natural killer (NK) cells and serum levels of monocyte-derived mediators were assessed initially for a baseline measurement and after 8 wks. RESULTS: The CBG-CS-2 group showed a significant 38.8 ± 17.6% enhancement from the baseline of NK cell cytotoxic activity relative to the placebo group after the administration of the capsules for 8 wks. (P < 0.019). CONCLUSION: The results suggest that the immune system functions well with CBG-CS-2 supplementation, perhaps with less accompanying inflammation. Thus, CBG-CS-2 is safe and effective for enhancing cell-mediated immunity in healthy adults. TRIAL REGISTRATION: This study was registered at Clinical Trials.gov ( NCT 02814617 ).

Mulberry leaf extract displays antidiabetic activity in db/db mice via Akt and AMP-activated protein kinase phosphorylation.

BACKGROUND: Augmenting glucose utilization in skeletal muscle via the phosphatidylinositol-3 kinase (PI3 kinase)/protein kinase B (Akt) pathway or the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway is necessary to regulate hyperglycemia in patients with type 2 diabetes mellitus. OBJECTIVE: We investigated the effect of mulberry leaf extract (MLE) on glucose uptake in skeletal muscle cells and explored its in vivo antidiabetic potential. DESIGN: Male db/db mice were treated with either MLE (50 mg/kg, 100 mg/kg, and 250 mg/kg) or metformin (100 mg/kg) for 8 weeks. RESULTS: MLE treatment stimulated glucose uptake, driven by enhanced translocation of glucose transporter 4 to cell membranes in L6 myotubes. These effects of MLE were synergistic with those of insulin and were abolished in the presence of PI3K inhibitor or AMPK inhibitor. In db/db mice, supplementation with MLE decreased fasting blood glucose and insulin levels and enhanced insulin sensitivity, with increases of p-Akt and p-AMPK in skeletal muscle. Moreover, MLE improved blood lipid parameters and attenuated hepatic steatosis in diabetic db/db mice. DISCUSSION: These findings suggest that MLE exerts antidiabetic activity through stimulating glucose disposal in skeletal muscle cells via the PI3K/Akt and AMPK pathways. CONCLUSIONS: MLE can potentially improve hyperglycemia and hepatic steatosis in patients with type 2 diabetes.

Temporally Robust Eye Movements through Task Priming and Self-referential Stimuli.

Studies have demonstrated connections between eye movements and attention shifts. However, little is known about the general factors that contribute to the self-consistency of idiosyncratic scanpaths as a function of attention shifts over time. The present work repeatedly measured human eye movements at various time intervals that ranged from less than one hour to one year between recording sessions. With and without task context, subjects observed multiple images with multiple areas of interest, including their own sporadically interspersed facial images. As reactions to visual stimuli, the eye movements of individuals were compared within and between subjects. We compared scanpaths with dynamic time warping and identified subjects based on the comparisons. The results indicate that within-subject eye movement comparisons remain more similar than between-subject eye movement comparisons over time and that task context and self-referential stimuli contribute to the consistency of idiosyncrasies in attention shift patterns.

Supplementation with Aspergillus oryzae-fermented kochujang lowers serum cholesterol in subjects with hyperlipidemia.

BACKGROUND & AIMS: Kochujang, a traditional fermented red pepper paste, is known for its hypocholesterolemic effect; however, these studies used non-commercial preparations of kochujang. In this study, we examined whether commercially-made kochujang in which Aspergillus oryzae (also known as koji) was used as a microorganism for fermentation has the same cholesterol-lowering effects. METHODS: Hyperlipidemic subjects (based upon criteria of 110 ∼ 190 mg/dL LDL cholesterol or 200 ∼ 260 mg/dL total cholesterol) who had not been diagnosed with any disease and met the inclusion criteria were recruited for this study. The 30 subjects were randomly divided into either the kochujang (n = 15) or placebo (n = 15) group. All subjects ingested either the kochujang pill (34.5 g/d) or a placebo three times daily during meals for 12 weeks. Outcomes included measurements of efficacy (total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglyceride) and safety (adverse events, laboratory tests, electrocardiogram, and vital signs). RESULTS: In the kochujang-supplemented group, subjects' total cholesterol level significantly decreased (from 215.5 ± 16.1 mg/dL to 194.5 ± 25.4 mg/dL, p = 0.001). LDL-C cholesterol levels were also decreased by kochujang supplementation (from 133.6 ± 14.8 mg/dL to 113.5 ± 23.1 mg/dL); however no significant difference was seen between groups (p = 0.074). There were no statistically significant differences in HDL-cholesterol and triglyceride levels between the supplemented and non-supplemented groups. None of the subjects complained of any adverse effects. CONCLUSIONS: These results indicate that A. oryzae-fermented kochujang elicits a significant hypocholesterolemic effect and might be useful for improving blood cholesterol levels in subjects at high risk for cardiovascular disease. CLINICAL TRIAL REGISTRATION: NCT01865370.

Reduction of blood lipid parameters by a 12-wk supplementation of aged black garlic: a randomized controlled trial.

OBJECTIVE: The cholesterol-lowering effects of garlic as part of a healthy diet remain controversial. The aim of this study was to investigate whether supplementation with aged black garlic (ABG) could improve blood lipid profiles in patients with mild hypercholesterolemia. METHODS: We conducted a double-blind, randomized placebo-controlled trial. Sixty participants were randomly assigned to receive either ABG or placebo twice daily (total 6 g/d) before consumption of a meal every morning and evening for 12 wk. During the study, two participants dropped out of the ABG group, and three participants dropped out of the placebo group. Thus, the effects of AGB on fasting blood levels of lipids were evaluated in 28 participants and compared with the placebo group (n = 27). RESULTS: Among lipid components, no significant differences in triglycerides, low-density lipoprotein cholesterol, total cholesterol, or free fatty acid levels were observed between the two groups. However, ABG increased high-density lipoprotein cholesterol levels compared with the placebo group at the end of the study. Moreover, a significant decrease in the levels of alipoprotein B and a significant increase in the ratio of low-density lipoprotein cholesterol/alipoprotein B were observed in the ABG group. No adverse effects were reported in any of the patients. CONCLUSION: ABG supplementation reduced atherogenic markers and thus may have a cardioprotective effect beyond the gold standard medication in patients with mild hypercholesterolemia.

Improved cognitive performance following supplementation with a mixed-grain diet in high school students: a randomized controlled trial.

OBJECTIVE: Adolescence is a stage of rapid growth, when rich nutritional supplementation is important. Maintaining optimal cognitive functioning is critical in high school students, who are under considerable academic pressure. The objectives of this study were to identify the effects of a 9-wk randomly assigned diet of mixed grains versus a regular diet on cognitive performance and on levels of plasma brain-derived neurotrophic factor (BDNF) and S100B, a calcium-binding protein produced by astroglial cells, in healthy high school students (grades 10 and 11). METHODS: In this 9-wk, single-blind, controlled study, subjects were randomly allocated to either a mixed-grain or a regular diet. Cognitive assessments and measurements of plasma BDNF and S100B levels were performed at baseline and after the 9-wk intake of a mixed-grain or regular diet. Computerized neuropsychological tests and self-rating scales were used for the cognitive assessments. RESULTS: Significant improvements in some neuropsychological tests were found after 9 wk in both the mixed-grain and the regular-diet groups, but the changes from baseline between the two groups were not significantly different. Significant impairments on the AX-continuous performance test were observed at the endpoint in the regular-diet group, and the changes from baseline between the two groups were also significantly different for this test. A significant difference in changes in BDNF levels was observed between the two groups. CONCLUSIONS: These results suggest that intake of mixed grains for 9 wk is beneficial for cognitive performance and plasma BDNF levels in high school students. These beneficial effects seem to be related to the prevention of cognitive deterioration in a mental-fatigue test with the mixed-grain diet, rather than cognitive enhancement per se.