Kidney vascular congestion exacerbates acute kidney injury in mice.

Heart failure is frequently accompanied by kidney failure and co-incidence of these organ failures worsens the mortality in patients with heart failure. Recent clinical observations revealed that increased kidney venous pressure, rather than decreased cardiac output, causes the deterioration of kidney function in patients with heart failure. However, the underlying pathophysiology is unknown. Here, we found that decreased blood flow velocity in peritubular capillaries by kidney congestion and upregulation of endothelial nuclear factor-κB (NF-κB) signaling synergistically exacerbate kidney injury. We generated a novel mouse model with unilateral kidney congestion by constriction of the inferior vena cava between kidney veins. Intravital imaging highlighted the notable dilatation of peritubular capillaries and decreased kidney blood flow velocity in the congestive kidney. Damage after ischemia reperfusion injury was exacerbated in the congestive kidney and accumulation of polymorphonuclear leukocytes within peritubular capillaries was noted at the acute phase after injury. Similar results were obtained in vitro, in which polymorphonuclear leukocytes adhesion on activated endothelial cells was decreased in flow velocity-dependent manner but cancelled by inhibition of NF-κB signaling. Pharmacological inhibition of NF-κB for the mice subjected by both kidney congestion and ischemia reperfusion injury ameliorated the accumulation of polymorphonuclear leukocytes and subsequent exacerbation of kidney injury. Thus, our study demonstrates the importance of decreased blood flow velocity accompanying activated NF-κB signaling in aggravation of kidney injury. Hence, inhibition of NF-κB signaling may be a therapeutic candidate for the vicious cycle between heart and kidney failure with increased kidney venous pressure.

Intratubular epithelial-mesenchymal transition and tubular atrophy after kidney injury in mice.

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-ß 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-ß 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.

Difference in fascicle behaviors between superficial and deep quadriceps muscles during isometric contractions.

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 < 0.05). Pennation increased during contraction at 60° for VL (P < 0.05), but not for VI. CONCLUSION: 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.

[Ocular findings in 304 children with Down syndrome].

PURPOSE: To identify the characteristics and frequency of ocular findings in Japanese children with Down syndrome. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Reliability and validity of the Japanese version of the Infant Breastfeeding Assessment Tool.

OBJECTIVE: To translate the Infant Breastfeeding Assessment Tool (IBFAT) into Japanese and confirm the reliability and validity of the Japanese version of IBFAT. DESIGN: The methodological study examining the reliability and validity of the Japanese version of the IBFAT. SETTING: A maternity hospital in Tokyo. PARTICIPANTS: Ten mother-newborn pairs were recruited for the reliability analysis. 101 mother-newborn pairs were recruited for the validity analysis. MEASUREMENTS AND FINDINGS: Reliability was verified by video recording and direct observation. The observers are one researcher, and 11 evaluators consisting of midwives and nurses. Amongst the 11 evaluators, six evaluators directly observed breastfeeding behaviours and five evaluators observed breastfeeding behaviours through video viewing. Regarding the inter-rater agreement, the intraclass correlation (ICC) between the researcher and six direct evaluators was 0.985 (95% confidence interval [CI]: 0.941-0.996) and that amongst five video viewing evaluators was 0.827 (95% CI: 0.647-0.945). In the intra-rater agreement, the lowest ICC amongst all those investigating IBFAT scores was 0.810 (95% CI: 0.433-0.948). In concurrent validity, the correlation coefficients between the IBFAT and Breastfeeding behaviour Assessment (BBA) scores on the first day after birth and the fourth or fifth day after birth (at discharge) were 0.66 (p < 0.001) and 0.40 (p < 0.001), respectively. In predictive validity, the medians and interquartile ranges (IQRs) of IBFAT scores at discharge were 11.0 (IQR: 11.0-12.0) and 11.0 (IQR: 11.0-12.0) for the breast and mixed milk groups at one-month check-up, respectively. While both median values were the same, the Mann-Whitney U test showed a significant difference. KEY CONCLUSIONS: The Japanese version of the IBFAT is valid and reliable for measuring feeding behaviour amongst newborns in the first week of life. IMPLICATIONS FOR PRACTICE: The Japanese version of the IBFAT can be available both in a clinical setting and in research to help support breastfeeding.

Relationship between trunk intramuscular adipose tissue content and prevalence of metabolic syndrome in middle-aged Japanese men.

OBJECTIVES: The aim of the present study was to examine the dose-response relationship between trunk tissue composition and prevalence of metabolic syndrome (MetS) in middle-aged Japanese men. METHODS: The 1026 men (between 35 and 59 y of age) who participated in the present study were divided into two groups: those with metabolic syndrome (MetS) and those without (non-MetS). Intramuscular adipose tissue (IntraMAT) content and the cross-sectional areas (CSAs) of visceral adipose tissue and skeletal muscle tissue were calculated using low-dose computed tomography images acquired at the level of the third lumbar vertebra. Height, body mass, body fat, waist circumference, the presence of MetS, and lifestyle habits were also assessed. RESULTS: IntraMAT content was significantly higher in MetS than in non-MetS men. A 10% increase in IntraMAT content correlated with the prevalence of MetS (odds ratio, 4.197; 95% confidence interval, 3.108-7.088; P < 0.001), even after adjustments for age, height, adjusted skeletal muscle CSA, sleeping time, alcohol consumption, exercise habit, and cigarette smoking. Skeletal muscle CSA did not correlate with the prevalence of MetS after adjustments for IntraMAT content and other cofactors. CONCLUSIONS: Increase in IntraMAT content, not in skeletal muscle CSA, significantly correlated with the prevalence of MetS. These results suggest that countermeasures against the accumulation of trunk IntraMAT effectively prevent MetS in middle-aged Japanese men.

Streptozotocin induces renal proximal tubular injury through p53 signaling activation.

Streptozotocin (STZ), an anti-cancer drug that is primarily used to treat neuroendocrine tumors (NETs) in clinical settings, is incorporated into pancreatic ß-cells or proximal tubular epithelial cells through the glucose transporter, GLUT2. However, its cytotoxic effects on kidney cells have been underestimated and the underlying mechanisms remain unclear. We herein demonstrated that DNA damage and subsequent p53 signaling were responsible for the development of STZ-induced tubular epithelial injury. We detected tubular epithelial DNA damage in NET patients treated with STZ. Unbiased transcriptomics of STZ-treated tubular epithelial cells in vitro showed the activation of the p53 signaling pathway. STZ induced DNA damage and activated p53 signaling in vivo in a dose-dependent manner, resulting in reduced membrane transporters. The pharmacological inhibition of p53 and sodium-glucose transporter 2 (SGLT2) mitigated STZ-induced epithelial injury. However, the cytotoxic effects of STZ on pancreatic ß-cells were preserved in SGLT2 inhibitor-treated mice. The present results demonstrate the proximal tubular-specific cytotoxicity of STZ and the underlying mechanisms in vivo. Since the cytotoxic effects of STZ against ß-cells were not impaired by dapagliflozin, pretreatment with an SGLT2 inhibitor has potential as a preventative remedy for kidney injury in NET patients treated with STZ.

Direct evidence of proximal tubular proliferation in early diabetic nephropathy.

Kidney hypertrophy is a common clinical feature in patients with diabetes and is associated with poor renal outcomes. Initial cell proliferation followed by cellular hypertrophy are considered the responsible mechanisms for diabetic kidney hypertrophy. However, whether similar responses against hyperglycemia continue in the chronic phase in diabetes is unclear. We performed lineage tracing analysis of proximal tubular epithelia using novel type 2 diabetic mice with a tamoxifen-inducible proximal tubule-specific fluorescent reporter. Clonal analysis of proximal tubular epithelia demonstrated that the labeled epithelia proliferated in type 2 diabetic mice. Based on the histological analysis and protein/DNA ratio of sorted labeled tubular epithelia, there was no evidence of cellular hypertrophy in type 2 diabetic mice. Lineage tracing and histological analyses of streptozocin-induced type 1 diabetes also revealed that cellular proliferation occurs in the chronic phase of type 1 diabetes induction. According to our study, epithelial proliferation accompanied by SGLT2 upregulation, rather than cellular hypertrophy, predominantly occurs in the hypertrophic kidney in both type 1 and type 2 diabetes. An increased number of SGLT2+ tubular epithelia may be an adaptive response against hyperglycemia, and linked to the hyper-reabsorption of sodium and glucose observed in type 2 diabetes patients.

Proximal tubular epithelia-specific transcriptomics of diabetic mice treated with dapagliflozin.

Based on recent clinical trials using sodium-glucose co-transporter 2 inhibitor (SGLT2i) demonstrating the significant improvement of outcomes of diabetic kidney disease (DKD), the paradigm shift from "glomerulocentric" to "tubule centric" pathophysiology in DKD progression has been highlighted. Several responsible mechanisms for renoprotective effects by SGLT2i have been proposed recently, but the changes in proximal tubule-specific gene expression by SGLT2i in diabetic mice have not been elucidated. We report the analysis of the proximal tubular-specific pathway, demonstrating the downregulation of oxidative phosphorylation in dapagliflozin-treated db/db mice, a type 2 diabetic model. After 8-week treatment of dapagliflozin for db/db mice having a proximal tubule-specific tdTomato reporter, tdTomato-positive cells were isolated by FACS. Pathway analysis of RNA sequencing of isolated tubular epithelia revealed that oxidative phosphorylation was downregulated in dapagliflozin-treated mice. However, depletion of renal tissue ATP content in db/db mice was ameliorated by dapagliflozin administration. Pimonidazole staining demonstrated renal cortical tissue hypoxia in db/db mice, which was improved by dapagliflozin administration. This study suggests that dapagliflozin can ameliorate the excessive oxygen and ATP consumption, and subsequent tissue hypoxia in the diabetic kidney, which may explain, in part, the responsible mechanisms of the renoprotective effects of dapagliflozin.

Comparison of metabolic risk factors, physical performances, and prevalence of low back pain among categories determined by visceral adipose tissue and trunk skeletal muscle mass in middle-aged men.

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.

Novel perspective on contractile properties and intensity-dependent verification of force-frequency relationship during neuromuscular electrical stimulation.

PURPOSE: The aims of the present study were: (a) to examine the effect of the stimulus intensity on force-frequency and torque fluctuation-frequency relationships during Neuromuscular electrical stimulation; and (b) to identify a novel parameter that can be used to evaluate muscle contractile properties. METHODS: Electrically elicited joint torque involving the quadriceps femoris muscle was recorded during neuromuscular electrical stimulation at two different stimulus intensities in 19 healthy men. Stimulation frequencies were set at 5-40 Hz with a duration of 10 s. Evoked joint torque was compared among all stimulation frequencies between the two stimulus intensities (68 and 113 V). The torque fluctuation at each stimulation frequency as the change in the contraction pattern was also compared between the intensities. Torque and torque fluctuation were normalized at each frequency by the largest torque or torque fluctuation, respectively. We extracted a novel parameter: the arrival point of tetanic contraction based on force-frequency and torque fluctuation-frequency curves. RESULTS: There were significant differences in normalized torque at 5-25 and 40 Hz and in normalized torque fluctuation at 15-30 and 40 Hz between the two stimulus intensities. Extracted parameters showed no significant difference between the intensities. CONCLUSION: The results suggest that force-frequency relationships during neuromuscular electrical stimulation are influenced by the intensity of stimulation applied to the quadriceps femoris muscle. However, we consider that it is possible to simultaneously evaluate contractile properties using the novel parameter.

Effect of milk fat globule membrane supplementation on motor unit adaptation following resistance training in older adults.

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.

Quadriceps echo intensity can be an index of muscle size regardless of age in 65 or more years old.

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.

Modulation of Neural and Muscular Adaptation Processes During Resistance Training by Fish Protein Ingestions in Older Adults.

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.

Diverse Receptor Tyrosine Kinase Phosphorylation in Urine-Derived Tubular Epithelial Cells from Autosomal Dominant Polycystic Kidney Disease Patients.

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.

Comparison of muscle quality and functional capacity between Japanese and Brazilian older individuals.

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.

Pharmacological inhibition of ataxia-telangiectasia mutated exacerbates acute kidney injury by activating p53 signaling in mice.

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.

Effect of knee joint angle on the neuromuscular activation of the quadriceps femoris during repetitive fatiguing contractions.

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.

Knee joint angle and vasti muscle electromyograms during fatiguing contractions.

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 (P<0·05). 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 (P<0·05), whereas those for the VL and VM were similar (P>0·05). 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.

Similarity of muscle synergies extracted from the lower limb including the deep muscles between level and uphill treadmill walking.

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.