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Background: Glucose dysmetabolism is an important risk factor for dementia. Objective: We investigated the associations of diabetes mellitus, the levels of glycemic measures, and insulin resistance and secretion measures with dementia and its subtypes in a cross-sectional study. Methods: In this study, 10,214 community-dwelling participants were enrolled. Hemoglobin A1c (HbA1c), the homeostasis model assessment (HOMA) for insulin resistance (HOMA-IR), the HOMA of percent β-cell function (HOMA-β), and the glycated albumin (GA) was evaluated. The associations of each measure with Alzheimer’s disease (AD) and vascular dementia (VaD) were investigated. Results: The multivariable-adjusted odds ratios (ORs) of AD were significantly higher in participants with diabetes mellitus than in those without diabetes (1.46 [95% CI: 1.08–1.97]). Higher HbA1c levels were significantly associated with AD at diabetes (≥6.5%) and even at prediabetes (5.7 %–6.4 %) levels; multivariable-adjusted ORs for AD in participants at the diabetes level were 1.72 (95% CI: 1.19–2.49), and those in participants at the prediabetes level were 1.30 (95% CI: 1.00–1.68), compared with those in normal participants. Moreover, higher GA levels were associated with AD. No associations were observed between the diabetic status or the levels of glycemic measures and VaD. In addition, no significant relationships were observed between insulin resistance and secretion measurements and AD and VaD. Conclusion: Our findings indicate that diabetes mellitus and hyperglycemia are significantly associated with AD, even in individuals at the prediabetes level.

Medication non-adherence in the elderly population is a major problem, preventing them from obtaining optimal therapeutic effects. Identifying the factors affecting medication adherence is crucial for improving and maintaining health among the elderly population and enhance healthcare economy. The purpose of this study was to examine the prevalence of self-reported medication adherence, and identify the associated factors and the influence of health-related quality of life (HRQOL) in the Japanese community-dwelling elderly population. This cross-sectional study was part of the Nakajima study and targeted inhabitants aged ≥60 years who underwent health examinations in 2017. Data regarding medication adherence were acquired through interviews and self-administered questionnaires. Medication adherence were assessed using a visual analog scale, and HRQOL was assessed by EuroQol five-dimensional questionnaire with 3 levels. Among the 455 participants, low and high medication adherence were seen in 9.7% and 66.2% of the participants, respectively (visual analog scores

2-Deoxy-scyllo-inosose (2DOI, [2S,3R,4S,5R]-2,3,4,5-tetrahydroxycyclohexan-1-one) is a biosynthetic intermediate of 2-deoxystreptamine-containing aminoglycoside antibiotics, including butirosin, kanamycin, and neomycin. In producer microorganisms, 2DOI is constructed from d-glucose 6-phosphate (G6P) by 2-deoxy-scyllo-inosose synthase (DOIS) with the oxidized form of nicotinamide adenine dinucleotide (NAD+). 2DOI is also known as a sustainable biomaterial for production of aromatic compounds and a chiral cyclohexane synthon. In this study, a one-pot enzymatic synthesis of 2DOI from d-glucose and polyphosphate was investigated. First, 3 polyphosphate glucokinases (PPGKs) were examined to produce G6P from d-glucose and polyphosphate. A PPGK derived from Corynebacterium glutamicum (cgPPGK) was found to be suitable for G6P production under ordinary enzymatic conditions. Next, 7 DOISs were examined for the one-pot enzymatic reaction. As a result, cgPPGK and BtrC, the latter of which is a DOIS derived from the butirosin producer Bacillus circulans, achieved nearly full conversion of d-glucose to 2DOI in the presence of polyphosphate.

Background Antioxidants like vitamins C and E may minimize the risk for Alzheimer's disease. Objective We examined whether vitamins C and E modify the apolipoprotein E (APOE) E4-related risks for developing cognitive decline. Methods We conducted a population-based prospective study including Japanese residents aged 65 years from Nakajima, Japan. The participants received an evaluation of cognitive function and underwent blood tests including tests for vitamins C and E levels and APOE phenotypes. The APOE E4-by-gender-by-vitamin C or E interactions on developing cognitive decline were analyzed. Results Of 606 participants with normal cognitive function determined using a baseline survey (2007-2008), 349 completed the follow up survey between 2014 and 2016. In women with APOE E4, significantly reduced risk for cognitive decline was observed for the highest blood vitamin C concentration tertile [multivariate OR 0.10 (95% CI 0.01-0.93)] compared with the lowest tertile. In men without APOE E4, significantly reduced risk for cognitive decline was observed for the highest blood vitamin E concentration tertile [multivariate OR 0.19 (0.05-0.74)] as compared with the lowest tertile. Conclusion Our results demonstrate significant beneficial effects of vitamins C and E in reducing the risk of cognitive decline in women with APOE E4 and men without APOE E4, respectively.

The efficacy of wearing [a] compression garment (CG) between repeated bouts of exercise within a same day has not been fully understood. The present study determined the effect of wearing a CG after strenuous exercise sessions (consisting of sprint exercise, resistance exercise, drop jump) twice a day on exercise performance, muscle damage, and inflammatory responses. Eleven physically active males (age, 22.7 ± 0.9 years; height, 175.7 ± 6.7 cm; body mass, 73.6 ± 10.2 kg; BMI, 23.8 ± 2.7 kg/m2) performed two trials (a randomized crossover design), consisting of the trial with either wearing a whole-body CG during post-exercise period (CG trial) or the trial with wearing a normal garment without specific pressure (CON trial). Two exercise sessions were conducted in the morning (09:00–10:00, Ex1) and afternoon (14:00–15:00, Ex2). Immediately after completing 60 min of each exercise, the subjects in the CG trial changed into a whole-body CG. Time-course changes in exercise performance (bench press power, jump performances, repeated sprint ability), blood variables (lactate, glucose, myoglobin, creatine kinase, interleukin-6, leptin), and scores of subjective feeling (fatigue, muscle soreness) were compared between the CG and CON trials before Ex1 (8:40), immediately before Ex2 (14:00, 4 h after Ex1), 4 h after Ex2 (19:00), and 24 h after the onset of Ex1 (9:00). Two bouts of exercise significantly decreased performances of counter movement jump (main effect for time: P = 0.04, F = 3.75, partial η 2 = 0.27) and rebound jump (main effect for time: P = 0.00, F = 12.22, partial η 2 = 0.55), while no significant difference was observed between the two trials (interaction: P = 0.10, F = 1.96, partial η 2 = 0.16 for counter movement jump, P = 0.93, F = 0.01, partial η 2 = 0.001 for rebound jump). Repeated sprint ability (power output during 10 × 6 s maximal sprint, 30-s rest periods between sprints) did not differ significantly between the two trials at any time points. Power output during bench press exercise was not significantly different between the two trials (interaction: P = 0.46, F = 0.99, partial η 2 = 0.09 for Ex1, P = 0.74, F = 0.38, partial η 2 = 0.04 for Ex2, P = 0.22, F = 1.54, partial η 2 = 0.13 for 24 h after the onset of Ex1). Serum myoglobin, creatine kinase, leptin, and plasma interleukin-6 were not significantly different between the two trials (interaction: P = 0.16, F = 2.23, partial η 2 = 0.18 for myoglobin; P = 0.39, F = 0.81, partial η 2 = 0.08 for creatine kinase; P = 0.28, F = 1.30, partial η 2 = 0.13 for leptin; P = 0.34, F = 1.05, partial η 2 = 0.12 for interleukin-6). Muscle soreness at 24 h during post-exercise period was significantly lower in the CG trial than in the CON trial for pectoralis major muscle (P = 0.04), while the value was inversely lower in the CON trial for hamstring (P = 0.047). Wearing a whole-body CG during the post-exercise period after two bouts of strenuous exercise sessions separated with 4 h of rest did not promote recovery of muscle function for lower limb muscles nor did it attenuate exercise-induced muscle damage in physically active males.

We have previously reported that ischemic animal models treated with a respiratory inhibitor, rotenon, show an increased voluntary alcohol intake. Although it is clear that ischemic brain, as a result of reduced-blood flow, shows pathological events and/or neuro-degenerations apparently, little is known of causal relationship between the mechanism of neural dysfunction and voluntary alcohol consumption. Authors have investigated effects of permanent two-vessel occlusion (p2VO) on rat voluntary alcohol drinking behavior. In first experiment the p2VO-treated rats showed an increase of voluntary alcohol drinking behavior, as compared with sham controls. Using brain microdialysis technique, increases of only nucleus accumbens (ACC) dopamine (DA) releases were suppressed in the p2VO-treated rats significantly, following the high K+ (40 mM) perfusion through the microdialysis probe membrane. Alcohol (200 mM) perfusion-induced DA and serotonin (5-HT) releases in the ACC of the p2VO-treated rats were suppressed significantly in the second experiment, as compared with the sham-treated rats. In third experiment p2VO-treated rats showed significant decreases of the contents of DA, not 5-HT, in the ACC, caudate-putamen (C/P), ventral tegmental area-substantia nigra (VT/SN) and lateral hypothalamus (LH). Dopaminergic neurons in the ACC showed more functional vulnerability against the p2VO treatments, as compared with the serotonergic neurons. An increase of alcohol intake in the p2VO-treated rats means the compensation for the neural degeneration of the dopaminergic system in the ACC consisted brain rewarding system. It was likely suggested that neural disturbance of higher functions involved with incomplete global brain ischemia leads the risk of an abnormal alcohol drinking in human.

BACKGROUND Carotid blowout syndrome (CBS) is among the fatal complications in head and neck cancer treatment. However, the optimal treatment for CBS has not been established yet. This study aimed to describe our experience with two patients at high risk of CBS who underwent common carotid artery (CCA) ligation at the proximal side of the bleeding point under local anesthesia and before CCA rupture, and to review and compare the medical records of these two patients against 10 CBS cases treated in our department. METHODS The institutional electronic medical record was searched, and clinical information was extracted for all patients who showed CBS from 2007 to 2017. Our treatment method was performed as follows. Ligation of the proximal side of the CCA was performed under local anesthesia. The CCA was identified and clamped with two bulldog forceps for 10 minutes to check for any adverse neurological symptoms. Subsequently, the CCA was ligated using 2-0 silk threads and sutured with an absorbable suture between the silk threads. However, ligation or occlusion of the external carotid artery by previous treatment is a prerequisite for this method. RESULTS Eight patients received interventions, with six patients undergoing prophylactic interventions before rupture. Four patients who did not undergo treatment died owing to CBS. Two patients who underwent treatment with the novel method did not experience re-bleeding, but their conditions deteriorated owing to cancer progression. CONCLUSION The present method is one of the treatment choices for CBS, especially in patients with an 'impending' risk of CBS.

Upper limb movements are indispensable for daily activities. Because of their complexity, the development of rehabilitation exercises using robot and haptic technologies paired with medical treatment is useful for the recovery and maintenance of stroke survivors. The "SEMUL" is a 2-DOF passive haptic system for upper-limb rehabilitation, developed to facilitate dexterity training during reaching exercises. The system provides objective and quantitative evaluation of performance and is entertaining to use, particularly when using the coin collecting software. Past studies have revealed the potential for conducting standardized evaluations using this software. In this study, we assessed trainees' concentration during training as an index of their level of entertainment and engagement with the program. The trainees were able-bodied older persons. The training scores were fed back to the trainees, but the scores were inflated from the mid-point of the training without notifying them, to stimulate their motivation to achieve higher scores. Electroencephalogram results confirmed that the subjects maintained their concentration during the tests.

The adenosine triphosphate–binding cassette (ABC) half-transporters Abcg5 and Abcg8 promote the secretion of neutral sterol into bile. Studies have demonstrated the diet-induced gene expression of these transporters, but the regulation of their trafficking when the nutritional status changes in the liver remains to be elucidated. Here, we generated a novel in vivo kinetic analysis that can monitor the intracellular trafficking of Abcg5/Abcg8 in living mouse liver by in vivo transfection of the genes of fluorescent protein-tagged transporters and investigated how hypernutrition affects the canalicular trafficking of these transporters. The kinetic analysis showed that lithogenic diet consumption accelerated the translocation of newly synthesized fluorescent-tagged transporters to intracellular pools in an endosomal compartment and enhanced the recruitment of these pooled gene products into the bile canalicular membrane in mouse liver. Because some ABC transporters are reported to be recruited from intracellular pools to the bile canaliculi by cyclic adenosine monophosphate (cAMP) signaling, we next evaluated the involvement of this machinery in a diet-induced event. Administration of a protein kinase A inhibitor, N-(2-{[3-(4-bromophenyl)−2-propenyl]amino}ethyl)−5-isoquinolinesulfonamide, decreased the canalicular expression of native Abcg5/Abcg8 in lithogenic diet–fed mice, and injection of a cAMP analog, dibutyryl cAMP, transiently increased their levels in standard diet–fed mice, indicating the involvement of cAMP signaling. Indeed, canalicular trafficking of the fluorescent-tagged Abcg5/Abcg8 was enhanced by dibutyryl cAMP administration. Conclusion: These observations suggest that diet-induced lipid loading into liver accelerates the trafficking of Abcg5/Abcg8 to the bile canalicular membrane through cAMP signaling machinery. (Hepatology 2015;62:1215-1226)

Many stroke survivors experience motor deficits. Rehabilitation is important for the maintenance and recovery of motor functions for activities of daily living. Motivated patients tend to show better rehabilitation effects. In this study, motor function was scored using the Simple Exercise Machine for Upper Limbs (SEMUL) rehabilitation system for upper limbs and the trainees were given feedback on their scores. Nine healthy participants took part in this study and aimed to use the SEMUL once a week for 6 months. We confirmed that their motivation was improved by seeing the changes in their scores.

Dietary inorganic phosphate (Pi) is the most important factor in the regulation of renal Pi excretion. Recent studies suggest the presence of an enteric-renal signaling axis for dietary Pi as well as the existence of a mechanism by which the intestine detects changes in luminal Pi concentrations. The mechanisms of intestinal Pi sensing, however, are unknown. In the present study, we focused on Pi depletion signals and investigated the effects of dietary components on intestinal Pi sensing. After feeding rats experimental diets for 3 days, we investigated urinary Pi excretion and plasma biochemical parameters. Renal Pi excretion was suppressed in rats fed a low-Pi diet (0.02% Pi). Elimination of dietary calcium (Ca) completely blocked the suppression of Pi excretion, suggesting that the presence of Ca is essential for the Pi depletion signal. Furthermore, a minimum Ca content of more than 0.02% was necessary for the Pi depletion signal. Magnesium, lanthanum, and strontium, which are agonists of calcium sensing receptor, instead of Ca, reduced Pi excretion. Therefore, dietary Ca appears to be important for the Pi depletion-sensing mechanism in the gastrointestinal tract. In addition, the calcium sensing receptor may be involved in the Pi depletion signal.

cope The molecular mechanisms underlying the potential health benefit effects of soybean proteins on obesity-associated metabolic disorders have not been fully clarified. In this study, we investigated the effects of soluble soybean protein peptic hydrolysate (SPH) on adipocyte differentiation by using 3T3-L1 murine preadipocytes. Methods and results The addition of SPH increased lipid accumulation during adipocyte differentiation. SPH increased the mRNA expression levels of an adipogenic marker gene and decreased that of a preadipocyte marker gene, suggesting that SPH promotes adipocyte differentiation. SPH induced antidiabetic and antiatherogenic adiponectin mRNA expression and secretion. Moreover, SPH increased the mRNA expression levels of insulin-responsive glucose transporter 4 and insulin-stimulated glucose uptake. The expression levels of peroxisome proliferator-activated receptor γ (PPARγ), a key regulator of adipocyte differentiation, during adipocyte differentiation were up-regulated in 3T3-L1 cells treated with SPH, and lipid accumulation during adipocyte differentiation induced by SPH was inhibited in the presence of a PPARγ antagonist. However, SPH did not exhibit PPARγ ligand activity. Conclusion These findings indicate that SPH stimulates adipocyte differentiation, at least in part, via the up-regulation of PPARγ expression levels. These effects of SPH might be important for the health benefit effects of soybean proteins on obesity-associated metabolic disorders.

Mutations in the apically located Na+-dependent phosphate (NaPi) cotransporter, SLC34A3 (NaPi-IIc), are a cause of hereditary hypophosphatemic rickets with hypercalciuria (HHRH). We have characterized the impact of several HHRH mutations on the processing and stability of human NaPi-IIc. Mutations S138F, G196R, R468W, R564C, and c.228delC in human NaPi-IIc significantly decreased the levels of NaPi cotransport activities in Xenopus oocytes. In S138F and R564C mutant proteins, this reduction is a result of a decrease in the Vmax for Pi, but not the Km. G196R, R468W, and c.228delC mutants were not localized to oocyte membranes. In opossum kidney (OK) cells, cell surface labeling, microscopic confocal imaging, and pulse-chase experiments showed that G196R and R468W mutations resulted in an absence of cell surface expression owing to endoplasmic reticulum (ER) retention. G196R and R468W mutants could be partially stabilized by low temperature. In blue native-polyacrylamide gel electrophoresis analysis, G196R and R468W mutants were either denatured or present in an aggregation complex. In contrast, S138F and R564C mutants were trafficked to the cell surface, but more rapidly degraded than WT protein. The c.228delC mutant did not affect endogenous NaPi uptake in OK cells. Thus, G196R and R468W mutations cause ER retention, while S138F and R564C mutations stimulate degradation of human NaPi-IIc in renal epithelial cells. Together, these data suggest that the NaPi-IIc mutants in HHRH show defective processing and stability.

Summary This study determined the effects of high-intensity interval training on the exercise-induced growth hormone (GH) responses, whole body and regional fat content. Twenty-four sedentary males were randomized to either a high-intensity interval training (HIT) group or a low-intensity continuous training (LT) group. The HIT group performed intermittent exercises at 85% of V ˙ O 2 max , whereas the LT group performed continuous exercise for 22 min at 45% of V ˙ O 2 max . Before and after 4 weeks of training, hormonal and metabolic responses to acute exercise were determined. Acute exercise significantly increased GH concentrations in both groups (p

Objective We examined metabolic and endocrine responses during rest and exercise in moderate hypoxia over a 7.5 h time courses during daytime. Methods Eight sedentary, overweight men (28.6±0.8 kg/m2) completed four experimental trials: a rest trial in normoxia (FiO2 = 20.9%, NOR-Rest), an exercise trial in normoxia (NOR-Ex), a rest trial in hypoxia (FiO2 = 15.0%, HYP-Rest), and an exercise trial in hypoxia (HYP-Ex). Experimental trials were performed from 8:00 to 15:30 in an environmental chamber. Blood and respiratory gas samples were collected over 7.5 h. In the exercise trials, subjects performed 30 min of pedaling exercise at 60% of VO2max at 8:00, 10:30, and 13:00, and rested during the remaining period in each environment. Standard meals were provided at 8:30, 11:00, and 13:30. Results The areas under the curves for blood glucose and serum insulin concentrations over 7.5 h did not differ among the four trials. At baseline, %carbohydrate contribution was significantly higher in the hypoxic trials than in the normoxic trials (P