The prevalence of type 2 diabetes mellitus (T2DM) has been increasing worldwide. Therefore, a novel therapeutic strategy by which to prevent T2DM is urgently required. Calorie restriction (CR) can retard the aging processes, and delay the onset of numerous age-related diseases including diabetes. Metabolic CR mimetics may be therefore included as novel therapeutic targets for T2DM. Sirtuin 1 (SIRT1), a NAD+-dependent histone deacetylase that is induced by CR, is closely associated with lifespan elongation under CR. SIRT1 regulates glucose/lipid metabolism through its deacetylase activity on many substrates. SIRT1 in pancreatic beta-cells positively regulates insulin secretion and protects cells from oxidative stress and inflammation, and has positive roles in the metabolic pathway via the modulation in insulin signaling. SIRT1 also regulates adiponectin secretion, inflammation, glucose production, oxidative stress, mitochondrial function, and circadian rhythms. Several SIRT1 activators, including resveratrol have been demonstrated to have beneficial effects on glucose homeostasis and insulin sensitivity in animal models of insulin resistance. Therefore, SIRT1 may be a novel therapeutic target for the prevention of T2DM, implicating with CR. In this review, we summarize current understanding of the biological functions of SIRT1 and discuss its potential as a promising therapeutic target for T2DM.
Adiponectin ; Aging ; Caloric Restriction ; Circadian Rhythm ; Diabetes Mellitus, Type 2 ; Glucose ; Histone Deacetylases ; Homeostasis ; Inflammation ; Insulin ; Insulin Resistance ; Metabolic Networks and Pathways ; Models, Animal ; Oxidative Stress ; Prevalence ; Sirtuin 1 ; Stilbenes

The prevalence of type 2 diabetes mellitus (T2DM) has been increasing worldwide. Therefore, a novel therapeutic strategy by which to prevent T2DM is urgently required. Calorie restriction (CR) can retard the aging processes, and delay the onset of numerous age-related diseases including diabetes. Metabolic CR mimetics may be therefore included as novel therapeutic targets for T2DM. Sirtuin 1 (SIRT1), a NAD+-dependent histone deacetylase that is induced by CR, is closely associated with lifespan elongation under CR. SIRT1 regulates glucose/lipid metabolism through its deacetylase activity on many substrates. SIRT1 in pancreatic beta-cells positively regulates insulin secretion and protects cells from oxidative stress and inflammation, and has positive roles in the metabolic pathway via the modulation in insulin signaling. SIRT1 also regulates adiponectin secretion, inflammation, glucose production, oxidative stress, mitochondrial function, and circadian rhythms. Several SIRT1 activators, including resveratrol have been demonstrated to have beneficial effects on glucose homeostasis and insulin sensitivity in animal models of insulin resistance. Therefore, SIRT1 may be a novel therapeutic target for the prevention of T2DM, implicating with CR. In this review, we summarize current understanding of the biological functions of SIRT1 and discuss its potential as a promising therapeutic target for T2DM.
Adiponectin ; Aging ; Caloric Restriction ; Circadian Rhythm ; Diabetes Mellitus, Type 2 ; Glucose ; Histone Deacetylases ; Homeostasis ; Inflammation ; Insulin ; Insulin Resistance ; Metabolic Networks and Pathways ; Models, Animal ; Oxidative Stress ; Prevalence ; Sirtuin 1 ; Stilbenes

Diabetic nephropathy is a leading cause of end stage renal disease and its occurance is increasing worldwide. The most effective treatment strategy for the condition is intensive treatment to strictly control glycemia and blood pressure using renin-angiotensin system inhibitors. However, a fraction of patients still go on to reach end stage renal disease even under such intensive care. New therapeutic targets for diabetic nephropathy are, therefore, urgently needed. Autophagy is a major catabolic pathway by which mammalian cells degrade macromolecules and organelles to maintain intracellular homeostasis. The accumulation of damaged proteins and organelles is associated with the pathogenesis of diabetic nephropathy. Autophagy in the kidney is activated under some stress conditions, such as oxidative stress and hypoxia in proximal tubular cells, and occurs even under normal conditions in podocytes. These and other accumulating findings have led to a hypothesis that autophagy is involved in the pathogenesis of diabetic nephropathy. Here, we review recent findings underpinning this hypothesis and discuss the advantages of targeting autophagy for the treatment of diabetic nephropathy.
AMP-Activated Protein Kinases ; Anoxia ; Autophagy* ; Blood Pressure ; Caloric Restriction ; Diabetic Nephropathies* ; Homeostasis ; Humans ; Critical Care ; Kidney ; Kidney Failure, Chronic ; Organelles ; Oxidative Stress ; Podocytes ; Renin-Angiotensin System

Taping is widely used by sports trainers to prevent injury and to protect affected sites post-injury. However, it is not clear whether taping affect the perception of somatosensory stimulation. We sought to clarify the effect of taping on somatosensory stimulation using somatosensory evoked potentials (SEPs). We recorded SEPs following transcutaneous electrical stimulation of the right medial forearm in ten healthy volunteers. SEPs were recorded from 9 electrodes on the scalp under control, elastic-taping and white-taping conditions. Subjects relaxed on a comfortable reclining seat without taping in the control condition, while they were subjected to taping along the muscle of forearm with tension (elastic-taping) and without tension (white-taping) in the taping conditions. Results showed that the peak amplitude of N140 did not differ significantly among the three conditions but the peak amplitude of P250 was significantly lower in the elastic-taping condition than control and white-taping conditions. Elastic-taping with tension along the muscles changes various afferent inputs from muscle spindle or skin, and this may affect the perception of somatosensory stimulation.

Taping is widely used in sports medicine to prevent injury, protect affected sites post injury and relieve pain. However, it is not clear whether taping affects the perception of noxious stimulation because in previous studies, it was difficult to selectively activate Aδ fibers. A recently developed, useful, new tool named intra-epidermal electrical stimulation (IES) can preferentially activate Aδ fibers. We aimed to clarify the effect of taping on pain-related somatosensory evoked potentials (pSEPs) using IES. We recorded pSEPs following IES of the right medial forearm in twelve healthy volunteers. pSEPs were recorded from 9 electrodes on the scalp under control, elastic-taping and white-taping conditions. Under the control condition, subjects relaxed on a comfortable reclining seat without taping, whereas under the taping conditions, they were subjected to taping along the forearm with tension (elastic-taping) and without tension (white-taping). Subjects were asked to assign a visual analog scale (VAS) score after each session. The peak amplitudes of N2-P2 were significantly lower under the elastic-taping and white-taping conditions than those under the control condition. VAS was significantly lower elastic-taping condition than those under the control and white-taping conditions. Moreover, there was a significant positive correlation between the amplitude of N2-P2 and VAS. We revealed that taping along the forearm decreased pSEPs and subjective pain perception under the white-taping and elastic-taping conditions. The underlying mechanism of pain relief was the distraction effect in both taping conditions. In addition, elastic-taping with tension changes afferent inputs mainly from the skin, and this might more effectively decrease the subjective pain perception than that achieved under the white-taping condition.

Background: Febrile neutropenia (FN) remains an important complication in pediatric cancer patients. The present study compared the efficacy of meropenem (MEPM) and piperacillin/tazobactam (PIPC/TAZ) with or without intravenous immunoglobulin (IVIG) as second-line therapy for FN in pediatric patients. Methods: As first-line treatment for FN, 394 episodes in 99 patients were randomly assigned to receive PIPC/TAZ (360 mg/kg/day, maximum 18 g/day) or MEPM (120 mg/ kg/day, maximum 3 g/day). Eighty-four episodes in 42 patients were judged as failures, and, thus, were enrolled for second-line treatment. In second-line treatment, antibiotics were switched to MEPM or PIPC/TAZ, and episodes were further randomized for treatment with or without concomitant IVIG at 100 mg/kg/day (maximum 5 g/day) for 3 consecutive days. Results: The total success rate of second-line treatment was 50.0% (52.0% in PIPC/ TAZ and 47.2% in MEPM with or without IVIG, P=0.826). The success rates of patients treated with (IVIG+ group) and without IVIG (IVIG− group) were 53.8 and 46.7%, respectively (P=0.662). In the IVIG+ group, the success rate of patients younger than 8 years old was 78.6%, which was significantly higher than that of those aged 8 years and older (40.0%, P=0.043). Conclusion PIPC/TAZ and MEPM were equally effective as second-line treatment. Concomitant IVIG was also effective, particularly in patients younger than 8 years.

Soccer is the most popular sport worldwide, with over 265 million participants. Soccer is unique in that the ball can be directed deliberately and purposefully with the head, an act referred to as ‘heading’. In recent years, there has been concern about the association between repetitive subconcussive head impacts associated with heading and chronic traumatic encephalopathy. Heading causes immediate changes in biochemical and electrophysiological markers of traumatic brain injury, and some studies have reported brain structural changes and dysfunction in former soccer players. In 2019, it was reported that the mortality associated with neurodegenerative diseases was about 3.5 times higher among former professional soccer players. Following that, in early 2020, the guidance have been published to limit heading by age in some regions including England and Scotland. In this review, we will expound the immediate and long-term effects of heading associated with chronic traumatic encephalopathy and the measures that should be taken into consideration in the practice of soccer instruction, based on the latest findings.

Objective：To investigate the physical functions of peripheral arterial disease (PAD）patients undergoing endovascular treatment (EVT), and their association with physical activity before EVT.Methods：One hundred and one PAD patients underwent EVT. Physical functions were specified as grip strength, walking speed, and the weight ratio of knee extension isometric muscle strength (KEIS). We divided the patients into 3 groups, based on the amount of physical activity per week：(a) low activity (0 kcal/week：n＝52), (b）moderate activity (0 kcal to less than 500 kcal/week：n＝22), and (c) high activity (more than 500 kcal/week：n＝27). Physical activity data were collected using an international standardized physical activity questionnaire. A multivariate regression analysis (cumulative logit model) was used to evaluate the association between physical activity (low activity, moderate activity, high activity) and KEIS＜0.4 kgf/kg.Results：The averages of the physical functions were：grip strength (kg；Men 28.1, Women 16.6), walking speed (m/s；Men 1.10, Women 0.96), KEIS (kgf/kg；Men 0.42, Women 0.28). The prevalence of KEIS＜0.4 kgf/kg was 56.4％ (n＝57). KEIS＜0.4 kgf/kg was not significantly different between low and moderate activity groups (Odds：0.99, p＝0.98). However, KEIS＜0.4 kgf/kg was significantly different between low and high activity groups (Odds：5.02, p＝0.007).Conclusion：Physical functions were lower in PAD patients undergoing EVT than in healthy adults of the same age, and KEIS was related to physical activity before EVT.

Objective：To investigate the physical functions of peripheral arterial disease (PAD) patients undergoing endovascular treatment (EVT), and their association with physical activity before EVT.Methods：One hundred and one PAD patients underwent EVT. Physical functions were specified as grip strength, walking speed, and the weight ratio of knee extension isometric muscle strength (KEIS). We divided the patients into 3 groups, based on the amount of physical activity per week：(a) low activity (0 kcal/week：n＝52), (b) moderate activity (0 kcal to less than 500 kcal/week：n＝22), and (c) high activity (more than 500 kcal/week：n＝27). Physical activity data were collected using an international standardized physical activity questionnaire. A multivariate regression analysis (cumulative logit model) was used to evaluate the association between physical activity (low activity, moderate activity, high activity) and KEIS＜0.4 kgf/kg.Results：The averages of the physical functions were：grip strength (kg；Men 28.1, Women 16.6), walking speed (m/s；Men 1.10, Women 0.96), KEIS (kgf/kg；Men 0.42, Women 0.28). The prevalence of KEIS＜0.4 kgf/kg was 56.4％ (n＝57). KEIS＜0.4 kgf/kg was not significantly different between low and moderate activity groups (Odds：0.99, p＝0.98). However, KEIS＜0.4 kgf/kg was significantly different between low and high activity groups (Odds：5.02, p＝0.007).Conclusion：Physical functions were lower in PAD patients undergoing EVT than in healthy adults of the same age, and KEIS was related to physical activity before EVT.