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Assessments of both neural and muscular adaptations during interventions would provide valuable information for developing countermeasures to age-related muscle dysfunctions. We investigated the effect of fish protein ingestion on training-induced neural and muscular adaptations in older adults. Twenty older adults participated 8 weeks of isometric knee extension training intervention. The participants were divided into two groups who took fish protein (n = 10, Alaska pollack protein, APP) or casein (n = 10, CAS). Maximal muscle strength during knee extension, lower extremity muscle mass (body impedance method), and motor unit firing pattern of knee extensor muscle (high-density surface electromyography) were measured before, during, and after the intervention. Muscle strength were significantly increased in both CAS (124.7 ± 5.8%) and APP (117.1 ± 4.4%) after intervention (p < .05), but no significant differences between the groups were observed (p > .05). Significant increases in lower extremity muscle mass from 0 to 8 weeks were demonstrated only for APP (102.0 ± 3.2, p < .05). Greater changes in motor unit firing pattern following intervention were represented in CAS more than in APP. These results suggest that nutritional supplementations could modulate neural and muscular adaptations following resistance training and fish protein ingestion preferentially induces muscular adaptation without the detectable neural adaptation in older adults.

Tubular atrophy is a common pathological feature of kidney fibrosis. Although fibroblasts play a predominant role in tissue fibrosis, the role of repairing tubular epithelia in tubular atrophy is unclear. We demonstrated the essential role of focal adhesion kinase (FAK)-mediated intratubular epithelial-mesenchymal transition (EMT) in the pathogenesis of tubular atrophy after severe ischemia-reperfusion injury (IRI). Actively proliferating tubular epithelia undergoing intratubular EMT were noted in the acute phase of severe IRI, resulting in tubular atrophy in the chronic phase, reflecting failed tubular repair. Furthermore, FAK was phosphorylated in the tubular epithelia in the acute phase of severe IRI, and its inhibition ameliorated both tubular atrophy and interstitial fibrosis in the chronic phase after injury. In vivo clonal analysis of single-labeled proximal tubular epithelial cells after IRI using proximal tubule reporter mice revealed substantial clonal expansion after IRI, reflecting active epithelial proliferation during repair. The majority of these proliferating epithelia were located in atrophic and nonfunctional tubules, and FAK inhibition was sufficient to prevent tubular atrophy. In vitro, transforming growth factor-β induced FAK phosphorylation and an EMT phenotype, which was also prevented by FAK inhibition. In an in vitro tubular epithelia gel contraction assay, transforming growth factor-β treatment accelerated gel contraction, which was suppressed by FAK inhibition. In conclusion, injury-induced intratubular EMT is closely related to tubular atrophy in a FAK-dependent manner.

This study aimed to investigate the effect of milk fat globule membrane (MFGM) supplementation on motor unit adaptation following resistance training in older adults. Twenty‐five older males and females took MFGM (n = 12) or a placebo (PLA; n = 12) while performing 8 weeks of isometric knee extension training. During the training, the motor unit firing pattern during submaximal contractions, muscle thickness, and maximal muscle strength of knee extensor muscles were measured every 2 weeks. None of the measurements showed significant differences in muscle thickness or maximal muscle strength (MVC) between the two groups (p > .05). Significant decreases in motor unit firing rate following the intervention were observed in PLA, that is, 14.1 ± 2.7 pps at 0 weeks to 13.0 ± 2.4 pps at 4 weeks (p = .003), but not in MFGM (14.4 ± 2.5 pps to 13.8 ± 1.9 pps). Motor unit firing rates in MFGM were significantly higher than those in PLA at 2, 4, 6, and 8 weeks of the intervention, that is, 15.1 ± 2.3 pps in MFGM and 14.5 ± 3.3 pps in PLA at 70% of MVC for motor units recruited at 40% of MVC at 6 weeks (p = .034). Significant differences in firing rates among motor units with different recruitment thresholds were newly observed following the resistance training intervention in MFGM, indicating that motor unit firing pattern is changed in this group. These results suggest that motor unit adaptation following resistance training is modulated by MFGM supplementation in older adults., The positive effect of milk fat globule membrane (MFGM) supplementation with exercise on age‐related dysfunctions in neuromuscular system had been reported in animal and human studies. This study found that MFGM supplementation with exercise can modify adaptations in motor unit firing pattern in older adults. Whereas the same exercise regimen was applied, different neural adaptation may be able to induce by ingestion of MFGM in older adults.

Backgrounds: The clinical features of autosomal dominant polycystic kidney disease (ADPKD) differ among patients even if they have the same gene mutation in PKD1 or PKD2. This suggests that there is diversity in the expression of other modifier genes or in the underlying molecular mechanisms of ADPKD, but these are not well understood. Methods: We primarily cultured solute carrier family 12 member 3 (SLC12A3)-positive urine-derived distal tubular epithelial cells from 6 ADPKD patients and 4 healthy volunteers and established immortalized cell lines. The diversity in receptor tyrosine kinase (RTK) phosphorylation by phospho-RTK array in immortalized tubular epithelial cells was analyzed. Results: We noted diversity in the activation of several molecules, including Met, a receptor of hepatocyte growth factor (HGF). Administration of golvatinib, a selective Met inhibitor, or transfection of small interfering RNA for Met suppressed cell proliferation and downstream signaling only in the cell lines in which hyperphosphorylation of Met was observed. In three-dimensional culture of Madin-Darby canine kidney (MDCK) cells as a cyst formation model of ADPKD, HGF activated Met, resulting in an increased total cyst number and total cyst volume. Administration of golvatinib inhibited these phenotypes in MDCK cells. Conclusion: Analysis of urine-derived tubular epithelial cells demonstrated diverse RTK phosphorylation in ADPKD, and Met phosphorylation was noted in some patients. Considering the difference in the effects of golvatinib on immortalized tubular epithelial cells among patients, this analysis may aid in selecting suitable drugs for individual ADPKD patients.

The DNA damage response after kidney injury induces cell cycle arrest in renal tubular epithelial cells, resulting in the secretion of pro-fibrotic cytokines, thereby promoting interstitial fibrosis in a paracrine manner. Phosphorylation of ataxia-telangiectasia mutated (ATM) is the initial step in the DNA damage response and subsequent cell cycle arrest; however, the effects of ATM inhibition on the injured kidney have not been explored. Pharmacological ATM inhibition by KU55933 in cisplatin-treated mice did not ameliorate, but instead exacerbated cisplatin-induced DNA damage and tubular injury, thereby increasing mortality. Analysis of isolated tubular epithelia by FACS from bigenic SLC34a1-CreERt2; R26tdTomato proximal tubular-specific reporter mice revealed that KU55933 upregulated p53 and subsequent pro-apoptotic signaling in tubular epithelia of cisplatin-treated mice, leading to marked mitochondrial injury and apoptosis. In addition, KU55933 attenuated several DNA repair processes after cisplatin treatment, including single-strand DNA repair and Fanconi anemia pathways, suggesting that DNA repair after dual treatment of cisplatin and KU55933 was not sufficient to prevent the cisplatin-induced tubular injury. Our study suggested that ATM inhibition does not increase DNA repair after cisplatin-induced DNA damage and exacerbates tubular injury through the upregulation of p53-dependent pro-apoptotic signaling. Acute kidney injury must be carefully monitored when ATM inhibitors become available in clinical practice in the future.

This study aimed to identify muscle synergies of the lower limb during treadmill running on level and inclined ground. Eight subjects ran on a treadmill at three speeds (2.5, 3.3, and 4.1 m/s) and two grades (level and 10% grade). Surface electromyographic (EMG) signals were recorded from 10 muscles of the lower limb, including deeper muscles such as vastus intermedius, adductor magnus, and adductor longus. Muscle synergies were extracted applying a non-negative matrix factorization algorithm, and relative co-activations across muscles and the temporal recruitment pattern were identified by muscle synergy vector and synergy activation coefficient, respectively. The scalar product between pairs of synergy vectors and synergy activation coefficients during level and uphill running conditions were analyzed as a similarity index, with values above 0.8 recognized as similar. Approximately 4 muscle synergies controlled the majority of variability in 10 EMGs during running, and were common between level and uphill conditions. At each running speed, inter-condition similarity was observed in synergy vector (r > 0.83) and synergy activation coefficients (r > 0.84) at each type of synergy. These results suggest that types of synergy are consistent between level and uphill running.

The present study compared metabolic risk factors, physical performances, and musculoskeletal impairment among categories determined by visceral adipose tissue (VAT) and trunk skeletal muscle (SM) mass in middle-aged Japanese men. In total, 1026 healthy Japanese males aged between 35 and 59 years were categorized into 4 groups according to the amount of VAT and SM in the trunk measured using low-dose computed tomography (LowVAT-HighSM, LowVAT-LowSM, HighVAT-HighSM, and HighVAT-LowSM). Height, body mass waist circumference, body fat, intramuscular adipose tissue (IntraMAT), subcutaneous adipose tissue, biochemical blood profiles (triglycerides, high-density lipoprotein cholesterol, fasting blood glucose, aspartate transaminase, alanine transaminase and γ-glutamyl trans peptidase), physical performances (trunk flexibility, the chair-stand test, two-step length and hand-grip strength), the prevalence of low back pain, and lifestyle habits for exercise, alcohol intake and smoking, were compared among the groups. The results showed that LowVAT-HighSM had significantly superior biochemical blood profiles and physical performances to the other groups. HighVAT-LowSM had significantly higher %IntraMAT and the prevalence of low back pain. The two-step length, which is an index of walking ability, significantly differed according to the four subject categories. These results indicate that metabolic risk factors, physical performances, and prevalence of low back pain in middle-aged Japanese men may differ among four categories determined by VAT and trunk SM.

The age-related decrease in human skeletal muscle mass; i.e. sarcopenia, has received much attention, but an age-related increase in the ratio of adipose tissue to muscle tissue has received noticeably less. A few studies have shown that ultrasonographic echo intensity, an index of the adipose-to-muscle ratio, is negatively associated with functional capacity, but the best parameters by which to predict this ratio have not yet been established for older individuals. The purpose of this study was to assess the relationships between quadriceps femoris (QF) echo intensity and demographic, functional and morphological characteristics of older men and women. Sixty-four healthy men (n = 27) and women (n = 37) aged 62–88 years (72.0 ± 5.0 years) participated in this study. The echo intensity and muscle thickness of the QF were calculated using ultrasonography. Sit-up, supine-up, sit-to-stand, 5-m maximal walk and 6-min walk tests were performed. There were no significant differences in QF echo intensity between sexes, but QF echo intensity was significantly correlated with QF muscle thickness. Stepwise multiple regression analysis with QF echo intensity as a dependent variable revealed QF muscle thickness, sit-to-stand test in men and age, and QF muscle thickness and sit-to-stand test in women, to be significant variables. These results suggest that QF echo intensity can be explained by QF muscle thickness, sit-to-stand and/or age in older men and women; however, an “age” effect was present only in men.

Muscle quality is well-known to decrease with aging and is a risk factor for metabolic abnormalities. However, there is a lack of information on race-associated differences in muscle quality and other neuromuscular features related to functional performance. This study aimed to compare muscle quality, function, and morphological characteristics in Japanese and Brazilian older individuals. Eighty-four participants aged 65–87 years were enrolled in the study (42 Japanese: 23 men, 19 women, mean age 70.4 years; 42 Brazilians: 23 men, 19 women, mean age 70.8 years). Echo intensity (EI) and muscle thickness (MT) of the quadriceps femoris were measured using B-mode ultrasonography. A stepwise multiple linear regression analysis with EI as a dependent variable revealed that MT was a significant variable for Japanese participants (R2 = 0.424, P = 0.001), while MT and subcutaneous adipose tissue (SCAT) thickness were significant variables for Brazilian participants (R2 = 0.490, P = 0.001). A second stepwise multiple linear regression analysis was performed after excluding MT and SCAT thickness from the independent variables. Sex and age for Japanese participants (R2 = 0.381, P = 0.001) and lean body mass and body mass index for Brazilian participants (R2 = 0.385, P = 0.001) were identified as significant independent variables. The present results suggest that MT is closely correlated with muscle quality in Japanese and Brazilian older individuals. Increases in muscle size may induce decreases in intramuscular adipose tissue and/or connective tissues, which are beneficial for reducing the risks of metabolic impairments in Japanese and Brazilian older individuals.

We assessed the effect of knee joint angle on the EMG amplitude and frequency of the four individual muscles in the quadriceps femoris during repetitive fatiguing maximum voluntary contractions (MVCs). Fifteen healthy men and women performed two fatiguing tasks consisting of 40 MVCs in flexion (80°) and extension (140˚) (full extension = 180˚). Neuromuscular activation of the vastus intermedius (VI), vastus lateralis (VL), vastus medialis (VM), and rectus femoris (RF) was recorded using surface electrodes, and median frequency (MF) and root mean square (RMS) of electromyographic (EMG) signals (normalized by pre-test MVCs) were calculated. MVCs significantly decreased from the 10th to the 40th repetition in both flexion and extension. The MFs of VI and VM in flexion and that of RF flexion and extension were significantly decreased after the 10th repetition. There were no significant changes in normalized EMG amplitude in any muscles specific to knee angle. Stepwise regression analysis suggested that predictive synergistic action may occur in RF/VM and RF/VI in flexion and in RF/VM in extension. This suggest that EMG MF of RF/VM is independent, but that of RF/VI and RF/VL is dependent upon knee joint angle, which may, in part, explain joint angle-specific muscle fatigue.

Introduction In this study we examined changes in fascicle length and pennation of vastus intermedius (VI) and vastus lateralis (VL) from rest to isometric contraction. Methods Fourteen healthy men performed submaximal (30% and 50% of maximal voluntary contraction; MVC) isometric knee extensions at 60° and 110° knee flexion (0° = full extension). Panoramic images of VL and VI were obtained at rest and during contractions to measure fascicle length and pennation using extended field-of-view ultrasonography, after confirmation that the technique could be used reliably during sustained submaximal isometric contractions. Results The relative change in fascicle length from rest to 50% MVC was greater in VI than VL at 110° (P

Although age-related deterioration of skeletal muscle strength and size has gained much attention, the age-related increase in adipose tissue within skeletal muscle has not received the same level of attention, especially in older individuals. It is not well known how echo intensity (EI), which is an index of intramuscular adipose tissue (IntraMAT) and connective tissue, is associated with demographic, functional, and morphological characteristics in older individuals. The purpose of this study was to assess the relationships between the EI of the quadriceps femoris (QF) and demographic, functional, and morphological characteristics in pre-old (65-74 years) and old (75 years or older) individuals. One hundred thirty-two men and women aged 65 to 74 years (45 men and 51 women; Pre-old group) or 75 years and older (17 men and 19 women, Old group) participated in this study. The EI and muscle thickness (MT) of the QF were measured using B-mode ultrasonography. Sit-up, supine-up, sit-to-stand, 5-m maximal walk, and 6-min walk tests were performed. The EI of the QF in the Old group (73.1 ± 9.0 a.u.) was significantly higher than that in the Pre-old group (67.6 ± 9.1 a.u.). The EI of the QF was significantly correlated with the MT of the QF in both the Pre-old (r = -0.542, P 0.01) and Old (r = -0.622, P 0.01) groups. Stepwise multiple linear regression analysis with the EI of the QF as a dependent variable showed that the MT of the QF was a significant variable in both the Pre-old and Old groups. These results suggest that MT is an extremely valuable factor for explaining the EI of the QF regardless of age group. Exercise interventions are recommended to decrease the risks of metabolic impairment by increasing muscle size and decreasing IntraMAT in individuals aged 65 years or older.

Background Older individuals have been shown to present muscle atrophy in conjunction with increased fat fraction in some muscles. The proportion of fat and connective tissue within the skeletal muscle can be estimated from axial B-mode ultrasound images using echo intensity (EI). EI was used to calculate the index of muscle quality. Walking, home-based weight-bearing resistance training, and its combinations are considered simple, easy, and practical exercise interventions for older adults. The purpose of this study was to quantify the effects of walking and walking with home-based resistance training on muscle quality of older individuals. Methods Thirty-one participants performed walking training only (W-group; 72 ± 5 years) and 33 participants performed walking and home-based resistance training (WR-group; 73 ± 6 years). This study was a non-randomized controlled trial with no control group. All participants were instructed to walk 2 or 3 sets per week for 10 weeks (one set: 30-min continuous walking). In addition, the WR-group performed home-based weight-bearing resistance training. EI was measured as a muscle quality index using axial B-mode ultrasound images of the rectus femoris and vastus lateralis of the mid-thigh. We further averaged these parameters to obtain the EI of the quadriceps femoris (QF). Participants further performed five functional tests: sit-ups, supine up, sit-to-stand, 5-m maximal walk, and 6-min walk. Results QF EI was significantly decreased in both groups after training (W-group 69.9 ± 7.4 a.u. to 61.7 ± 7.0 a.u., WR-group 64.0 ± 9.5 a.u. to 51.1 ± 10.0 a.u.; P

We previously developed a novel technique to record surface electromyography (EMG) of the vastus intermedius (VI) in men. The purpose of the present study was to assess whether this technique can be applied to women in the same way. We measured the subcutaneous fat thickness at the site of electrode placement on VI using ultrasonography. Nine men and ten women performed isometric knee extensions at 25%, 50%, 75%, and 100% of the maximal voluntary contraction. During the tasks, surface EMG signals were recorded from the superficial region of VI with interelectrode distances (IEDs) of 10 mm (IED-10) and 20 mm (IED-20). The subcutaneous fat thickness in women was significantly greater than in men (women: 8.7 ± 2.1 mm; men: 5.6 ± 1.6 mm, p < 0.01). However, the amplitude and frequency of the EMG signal of VI at the different force levels were not affected by IEDs in either sex. These results suggest that surface EMG recording of VI with both IED-10 and IED-20 would be applicable to relatively lean women with a similar sensitivity to that in men.

This study aimed to examine muscle synergies involving the deeper muscles of the lower limb during level and uphill treadmill walking. Seven men and five women walked on a treadmill at three speeds (60, 80, and 100m/min) and two grades (level and 10% grade). Surface electromyographic (EMG) signals were recorded from 10 muscles of the lower limb, including vastus intermedius, adductor magnus, and adductor longus. Muscle synergies were extracted applying non-negative matrix factorization, and the relative co-activation across muscles and the temporal information of synergy recruitment were identified by the muscle synergy vector and synergy activation coefficient, respectively. Correlation coefficients between a pair of synergy vectors during level and uphill walking were analyzed as a similarity index, with the similarity criterion at r=0.76. Changes in synergy activation coefficients between the walking conditions were evaluated by cross-correlation analysis. The mean number of synergies ranged from 3.8 to 4.0 across all conditions, and they were not significantly different between level and uphill walking conditions. Similarity between walking conditions was high (r>0.76) for three muscle synergies, but not for one synergy that mainly consisted of the quadriceps femoris. The inter-condition similarity of the synergy activation coefficients was high for the four synergies, and a significant lag time for synergy 2, which consisted mainly of the activity of medial gastrocnemius, was found at 60 and 80m/min. The muscle synergies extracted from the lower limb involving the deeper muscles appear to be consistent during level and uphill treadmill walking.

The crystal structure and charge density of (Ba0.5Sr0.5)(Co0.8Fe0.2)O2.33, a promising cathode material for solid oxide fuel cells with lower operating temperatures, were investigated by the Rietveld refinement method and the maximum entropy method (MEM) using neutron and synchrotron X-ray diffraction data. The crystal structure of (Ba0.5Sr0.5)(Co0.8Fe0.2)O2.33 was refined by using the orthorhombic Pnma space group and the split atom model to cation sites. The occupancy of O1 ( 4 c ) and O2 ( 8 d ) sites are 0.59 and 0.87, respectively. From the MEM analysis, we found that (Ba0.5Sr0.5)(Co0.8Fe0.2)O2.33 possessed both covalent and ionic bonds.

We compared vasti muscle electromyograms for two knee joint angles during fatiguing tetanic contractions. Tetanic contraction of the knee extensors was evoked for 70 s by electrical stimulation of the femoral nerve at knee joint angles of 60° (extended, with 0° indicating full extension) and 110° (flexed) in eight healthy men. Surface electromyography was recorded from the vastus intermedius (VI), vastus lateralis (VL) and vastus medialis (VM) muscles. Knee extension force and M-wave amplitudes and durations were calculated every 7 s, which were normalized by the initial value. Normalized knee extension force was decreased at the flexed knee joint angle compared with that of the extended knee joint angle (P0·05). Decreased normalized M-wave amplitude and increased normalized M-wave duration of the VI were greater at the flexed knee joint angle than the extended knee joint angle (P0·05), whereas those for the VL and VM were similar (P0·05). These results suggest that peripheral fatigue profiles of the VI might be greater at the flexed than the extended knee joint angles, but that of VL and VM might be similar in the tested range of knee joint angles (i.e. 60°-110°) during continuous tetanic contraction induced by electrical stimulation. Therefore, greater reduction of knee extension force at the flexed knee joint angle than the extended knee joint angle may reflect fatigue development of the VI more than other quadriceps femoris components.

In this study we examined changes in fascicle length and pennation of vastus intermedius (VI) and vastus lateralis (VL) from rest to isometric contraction.Fourteen healthy men performed submaximal (30% and 50% of maximal voluntary contraction; MVC) isometric knee extensions at 60° and 110° knee flexion (0° = full extension). Panoramic images of VL and VI were obtained at rest and during contractions to measure fascicle length and pennation using extended field-of-view ultrasonography, after confirmation that the technique could be used reliably during sustained submaximal isometric contractions.The relative change in fascicle length from rest to 50% MVC was greater in VI than VL at 110° (P 0.05). Pennation increased during contraction at 60° for VL (P 0.05), but not for VI.Muscle-dependent fascicle behaviors were observed during contraction. These findings may provide a mechanistic underpinning for differences in sarcomere length changes, relative force contribution, and blood flow during contraction.

The proton conductivity of (Ba1−xLax)2In2O5+x system has been investigated as a function of the La content, temperature and amount of absorbed water. The proton conductivity increased with La content up to x = 0.10, to reach a maximum of 1.12 × 10−5 (S/cm) at 400 °C. From that point on, it decreased. From the results of thermogravimetry and mass spectra, we confirmed that the water was absorbed in the (Ba1−xLax)2In2O5+x system, in a maximum quantity of 0.14 mol/mol (sample). The proton conductivity increased monotonically with the quantity of water uptake, suggesting that this variable is one of the dominant parameter of proton conductivity in this system.

To identify the characteristics and frequency of ocular findings in Japanese children with Down syndrome.A total of 304 Japanese children with Down syndrome at an average age of 7 years and 4 months were examined for ocular findings from June 2009 to January 2011.Most had hyperopia (69.1%) and astigmatism (58.5%). Both normal and oblique astigmatism were common. Spectacles were necessary in 91.3%. The average visual acuity at 8 years was 0.305 logMAR. Under 6 years, stripe and picture visual acuity charts were useful. Strabismus (36.5%, esotorpia 23.3%), nystagmus (25.7%), stereopsis (46.0%), entropion of eyelids (18.8%), cataract (10.5%), and corneal disease (3 cases) were found. Medullated nerve fibers (3 cases), pseudo disc edema (2 cases), and other retinal changes including Leber congenital amaurosis like chorioretinal degeneration (3 cases) were also found.The high incidence of refractive errors and strabisums in Down syndrome were confirmed. These must be treated during the sensitive period of visual development. For other ocular findings intensive ophthalmic care is important for children with Down syndrome from the time of infancy.