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ABSTRACT Aims/Introduction Insulin resistance syndrome and lipoatrophic diabetes are rare conditions characterized by the development of treatment‐refractory diabetes with severe insulin resistance. We recently conducted a 24 week, multicenter, single‐arm trial (EMPIRE‐01) that demonstrated a certain level of effectiveness and safety of empagliflozin for these conditions. To evaluate treatment safety over a longer period, we have now performed an additional 28 week trial (EMPIRE‐02) that followed on from EMPIRE‐01. Materials and Methods The primary and secondary outcomes were safety and efficacy evaluations, respectively. All eight subjects of the EMPIRE‐01 trial participated in EMPIRE‐02. Results Twenty adverse events (AEs) were recorded among five individuals during the combined 52 week treatment period of both trials. Whereas one case of chronic hepatitis B was moderate in severity, all other AEs were mild. There were thus no serious AEs or events necessitating discontinuation or suspension of treatment or a reduction in drug dose. Whereas ketoacidosis or marked increases in serum ketone body levels were not observed, the mean body mass of the subjects was decreased slightly after completion of EMPIRE‐02. The improvement in mean values of glycemic parameters observed in EMPIRE‐01 was not sustained in EMPIRE‐02, mostly because of one individual whose parameters deteriorated markedly, likely as a result of nonadherence to diet therapy. The improvement in glycemic parameters was sustained during EMPIRE‐02 after exclusion of this subject from analysis. Conclusions Empagliflozin demonstrated a certain level of safety and efficacy for the treatment of insulin resistance syndrome and lipoatrophic diabetes over 52 weeks, confirming its potential as a therapeutic option.

Abstract This study aimed to investigate how intermittent hyperoxic exposure (three cycles of 21% O2 [10 min] and 30% O2 [15 min]) affects exercise performance in mice. Three hours after the acute exposure, there was an observed increase in mRNA levels of phosphofructokinase (Bayes factor [BF] ≥ 10), mitochondrial transcription factor‐A (BF ≥10), PPAR‐α (BF ≥3), and PPAR‐γ (BF ≥3) in the red gastrocnemius muscle (Gr). Four weeks of exercise training under intermittent (INT), but not continuous (HYP), hyperoxia significantly (BF ≥30) increased maximal exercise capacity compared to normoxic exercise‐trained (ET) group. INT group exhibited significantly higher activity levels of 3‐hydroxyacyl‐CoA‐dehydrogenase (HAD) in Gr (BF = 7.9) compared to ET group. Pyruvate dehydrogenase complex activity levels were significantly higher in INT group compared to ET group in white gastrocnemius, diaphragm, and left ventricle (BF ≥3). NT‐PGC1α protein levels in Gr (BF = 7.7) and HAD activity levels in Gr (BF = 6.9) and soleus muscles (BF = 3.3) showed a significant positive correlation with maximal work values. These findings suggest that exercise training under intermittent hyperoxia is a beneficial strategy for enhancing endurance performance by improving fatty acid and pyruvic acid utilization.

Optical wireless power transmission (OWPT) attracts attention because it enables wireless power transfer over longer distances than current wireless power transfer methods, irradiating laser light to a light-receiving element. In this study, an OWPT system was investigated under water and deep seawater using visible lasers with low optical absorption loss in water. Three laser beams (450 nm, 532 nm, and 635 nm) were transmitted through 30 cm, 60 cm, and 90 cm long tanks filled with tap water and deep seawater and were irradiated to 1.0 × 1.0 cm2 GaInP solar cells. The light reaching rate (ηop) of laser light and the system efficiency (ηsys) of the system (excluding the laser efficiency) were investigated. GaInP solar cells showed photo-electric conversion efficiencies of 30.6%, 40.3%, and 39.3% for 450 nm, 532 nm, and 635 nm irradiations, respectively. As a result, a 532 nm laser through a 90 cm water tank in tap water showed a 78.4% ηop and a 30.8% ηsys. Under deep seawater, a 532 nm laser through a 90 cm tank exhibited a 58.3% ηop and a 23.5% ηsys. A 532 nm green laser showed a higher efficiency than the other 450 nm and 635 nm lasers in this underwater system using GaInP solar cells.

ABSTRACT Aims/Introduction The aim of the study was to compare two continuous glucose monitoring (CGM) systems, intermittently scanned CGM (isCGM) and real‐time CGM (rtCGM), to determine which system achieved better glycemic control in pediatric patients. Materials and Methods We carried out a retrospective cohort study of children and adolescents with type 1 diabetes, and compared the time in range (70–180 mg/dL), time below range (180 mg/dL), and estimated glycated hemoglobin levels between patients on isCGM and rtCGM. Results Of the 112 participants, 76 (67.9%) used isCGM and 36 (32.1%) used rtCGM for glycemic management. Patients on rtCGM had significantly greater time in range (57.7 ± 12.3% vs 52.3 ± 12.3%, P = 0.0368), and had significantly lower time below range (4.3 ± 2.7% vs 10.2% ± 5.4%, P

Abstract Aims/Introduction We examined the impact of scanning frequency with flash glucose monitoring on glycemic control in children and adolescents with type 1 diabetes. Materials and Methods The study included 85 patients, aged 14.0 ± 0.5 years, with type 1 diabetes. The median time in the target glucose range (TIR) and glycosylated hemoglobin (HbA1c) values were 50.0 ± 1.4% and 7.5 ± 0.1%, respectively. Results The median scanning frequency using flash glucose monitoring was 12.0 ± 0.4 times/day. Scanning frequency showed a significant positive correlation with TIR and an inverse correlation with HbA1c. Scanning frequency was identified to be the determinant of TIR and HbA1c by using multivariate analysis. The participants whose scanning frequency was 12 times/day were categorized as the high‐frequency group (n = 45). Patients in the high‐frequency group were more likely to be treated with insulin pumps compared with those in the low‐frequency group; however, this difference was not significant (21.3 vs 5.3%, P = 0.073). The high‐frequency group showed significantly greater TIR than the low‐frequency group (57 ± 1.6 vs 42 ± 1.7%, P = 0.002). Furthermore, the high‐frequency group showed significantly lower HbA1c levels than the low‐frequency group (6.8 ± 0.1 vs 8.0 ± 0.1%, P 12 times/day might contribute to better glycemic outcomes in real‐world practice in children with type 1 diabetes.

Abstract This study was designed to (1) investigate the effects of acute exercise under intermittent hypoxia on muscle mRNA and protein levels, and (2) clarify the mechanisms by which exercise under intermittent hypoxia improves endurance capacity. Experiment‐1: Male mice were subjected to either acute endurance exercise, exercise under hypoxia (14% O2), exercise under intermittent hypoxia (Int, three cycles of room air [10 min] and 14% O2 [15 min]). At 3 h after exercise under intermittent hypoxia, sirtuin‐6 mRNA levels and nuclear prolyl hydroxylases‐2 protein levels were significantly upregulated in white gastrocnemius muscle in the Int group. Experiment‐2: Mice were assigned to sedentary control (Sed), normoxic exercise‐trained (ET), hypoxic exercise‐trained (HYP) or exercise‐trained under intermittent hypoxia (INT) groups. Exercise capacity was significantly greater in the INT group than in the ET and HYP group. Activity levels of citrate synthase were significantly greater in the INT group than in the HYP group in soleus (SOL) and red gastrocnemius muscles. In SOL, nuclear N‐terminal PGC1α levels were considerably increased by the INT training (95% confidence interval [CI]: 1.09–1.79). The INT significantly increased pyruvate dehydrogenase complex activity levels in left ventricle (LV). Monocarboxylate transporter‐4 protein levels were significantly increased after the INT training in LV. Capillary‐to‐fiber ratio values were significantly increased in SOL and were substantially increased in LV (CI: 1.10–1.22) after the INT training. These results suggest that exercise training under intermittent hypoxia represents a beneficial strategy for increasing endurance performance via improving metabolic properties and capillary profiles in several hind‐leg muscles and the heart.

Abstract Hyperbaric exposure (1.3 atmospheres absolute with 20.9% O2) for 1 h a day was shown to improve exercise capacity. The present study was designed to reveal whether the daily exposure time affects exercise performance and metabolism in skeletal and cardiac muscles. Male mice in the training group were housed in a cage with a wheel activity device for 7 weeks from 5 weeks old. Trained mice were then subjected to hybrid training (HT, endurance exercise for 30 min followed by sprint interval exercise for 30 min). Hyperbaric exposure was applied following daily HT for 15 min (15HT), 30 min (30HT), or 60 min (60HT) for 4 weeks. In the endurance capacity test, maximal work values were significantly increased by 30HT and 60HT. In the left ventricle (LV), activity levels of 3‐hydroxyacyl‐CoA‐dehydrogenase, citrate synthase, and carnitine palmitoyl transferase (CPT) 2 were significantly increased by 60HT. CPT2 activity levels were markedly increased by hyperbaric exposure in red gastrocnemius (Gr) and plantaris muscle (PL). Pyruvate dehydrogenase complex activity values in PL were enhanced more by 30HT and 60HT than by HT. Protein levels of N‐terminal isoform of PGC1α (NT‐PGC1α) protein were significantly enhanced in three hyperbaric exposed groups in Gr, but not in LV. These results indicate that hyperbaric exposure for 30 min or longer has beneficial effects on endurance, and 60‐min exposure has the potential to further increase performance by facilitating fatty acid metabolism in skeletal and cardiac muscles in highly trained mice. NT‐PGC1α may have important roles for these adaptations in skeletal muscle.

Abstract The author previously reported that short‐duration intermittent hypoxia had additive effects on improvements in endurance capacity by enhancing fatty acid metabolism. The present study was designed to investigate the effects of short‐duration intermittent hypoxia on endurance capacity, metabolic enzyme activity, and protein levels associated with mitochondrial biogenesis in well‐trained mice. Mice in the training group were housed in a cage with a running wheel for 7 weeks from 5 weeks old. Voluntary running markedly increased maximal work values by 5.0‐fold. Trained mice were then subjected to either endurance treadmill training (ET) for 60 min or hybrid training (HT, ET for 30 min followed by sprint interval exercise (5‐sec run‐10‐sec rest) for 30 min) with (H‐ET or H‐HT) or without (ET or HT) short‐duration intermittent hypoxia (4 cycles of 12–13% O2 for 15 min and 20.9% O2 for 10 min) for 4 weeks. Maximal endurance capacity was markedly greater in the H‐ET and H‐HT than ET and HT groups, respectively. H‐ET and H‐HT increased activity levels of 3‐hydroxyacyl‐CoA‐dehydrogenase in oxidative muscle portion and pyruvate dehydrogenase complex in glycolytic muscle portion. These activity levels were significantly correlated with maximal endurance capacity. Protein levels of dynamin‐related protein‐1 were increased more by H‐ET and H‐HT than by ET and HT, but were not significantly correlated with maximal work. These results suggest that intermittent hypoxic exposure has beneficial effects on endurance and hybrid training to improve the endurance capacity via improving fatty acid and pyruvate oxidation in highly trained mice.

In this study, simulations are conducted using a network model to examine how the macroscopic network in the brain is related to the complexity of activity for each region. The network model is composed of multiple neuron groups, each of which consists of spiking neurons with different topological properties of a macroscopic network based on the Watts and Strogatz model. The complexity of spontaneous activity is analyzed using multiscale entropy, and the structural properties of the network are analyzed using complex network theory. Experimental results show that a macroscopic structure with high clustering and high degree centrality increases the firing rates of neurons in a neuron group and enhances intraconnections from the excitatory neurons to inhibitory neurons in a neuron group. As a result, the intensity of the specific frequency components of neural activity increases. This decreases the complexity of neural activity. Finally, we discuss the research relevance of the complexity of the brain activity.

In recent years, many experiments have investigated the impact of dietary amino acid supplementation on improvements in muscle strength and endurance capacity. However, it is unclear whether this supplementation causes vascular remodelling in skeletal muscle. This review focused on the effects of L-arginine and/or L-ornithine supplementation on capillary growth in cardiac and skeletal muscles. Although the chronic administration of 4% L-arginine did not improve capillarization in rat cardiac and hind-leg muscles, it facilitated exercise-induced capillary growth via vascular endothelial growth factor (VEGF) protein upregulation. In middle-aged rats, moderate intensity endurance training for 6 weeks did not cause capillary growth, whereas training with L-arginine supplementation led to an improvement in capillarization in the hind-leg muscle and left ventricle by promoting VEGF and endothelial nitric oxide synthase (eNOS) protein expression. The administration of L-arginine and L-ornithine for 6 weeks caused a marked increase in capillarization in rat skeletal muscle via the downregulation of endostatin and upregulation of VEGF-R2 protein expression. Moreover, this supplementation facilitated exercise-induced improvements in capillarization in the hind-leg muscles via the downregulation of endostatin and upregulation of VEGF and eNOS protein levels. The evidence presented in this review indicates that L-arginine and/or L-ornithine administration may facilitate capillary growth and endurance exercise capacity. Furthermore, this supplementation may be a useful therapeutic intervention for ischemic-related diseases.