Non-contractile Tissue Research Articles

MicroRNA-145-5p restricts cardiac scar resolution during cardiac regeneration

Abstract Background Human hearts have a very limited capacity to renew cardiomyocytes following injury. The lost myocardium is permanently replaced with noncontractile fibrotic tissue, consequently leading to heart failure. In contrast, zebrafish retain cardiac regenerative capacity during their lifetime. After injury, zebrafish hearts undergo transient fibrotic scarring that subsequently resolves and is replaced with new cardiomyocytes over time. Thus, understanding the molecular mechanisms governing cardiac scar resolution in zebrafish could offer insights into enhancing the regenerative capacities of human hearts. Objective We aimed to decipher the molecular pathways associated with zebrafish cardiac scar resolution. Methods We investigated the mRNA and miRNA responses to injury at 14 days post-injury by high-throughput transcriptome profiling of RNAs isolated from healthy or cryoinjured hearts. The prediction of miRNA-mRNA interactions was performed to identify the most differentially expressed miRNAs and their target genes. These miRNAs and genes were validated in zebrafish regenerating hearts and in the left ventricles of ischemic cardiomyopathy or dilated cardiomyopathy patients. The potential role of identified miRNAs in cardiac scar resolution was investigated in human cardiac fibroblasts. Results Principal component analyses identify two distinct clusters in both the mRNAome and miRNAome corresponding to healthy and injured hearts, indicating significant changes in transcriptome profiles during zebrafish cardiac regeneration. Gene set enrichment analyses indicate that molecular pathways involved in extracellular matrix organization and inflammatory response are markedly activated whereas genes associated with mitochondrial organization and oxidative phosphorylation are downregulated in injured hearts. We observed the downregulation of miR-145-5p and the upregulation of procollagen V in the injured hearts. In contrast to zebrafish, in the left ventricles of ischemic cardiomyopathy patients, miR-145-5p is significantly upregulated and procollagen V α1 is downregulated. Theoretical prediction of miRNA-mRNA interactions indicates procollagen V α1 is negatively correlated with miR-145-5p. Overexpression of miR-145-5p in human cardiac fibroblasts downregulates collagen V α1 and alpha smooth muscle actin, upregulates procollagen I and matrix metalloproteinase 9, and inhibits cell proliferation and migration. In contrast, inhibition of miR-145-5p upregulates collagen V α1 and alpha smooth muscle actin, downregulates procollagen I and matrix metalloproteinase 9, and stimulates cell proliferation and migration. Conclusion Our study suggests that miR-145-5p may play a role in the suppression of myofibroblast transdifferentiation via collagen V α1, which restricts scar resolution and cardiac repair.

Muscle Fibrosis, NF-κB, and TGF-β Are Differentially Altered in Two Models of Paralysis (Botox Versus Neurectomy).

Objective: Volumetric muscle loss results in intramuscular axotomy, denervating muscle distal to the injury and leading to paralysis, denervation, and loss of muscle function. Once the nerve is damaged, paralyzed skeletal muscle will atrophy and accumulate noncontractile connective tissue. The objective of this study was to determine differences in connective tissue, atrophy, and inflammatory signaling between two paralysis models, botulinum toxin (Botox), which blocks acetylcholine transmission while keeping nerves intact, and neurectomy, which eliminates all nerve-to-muscle signaling. Approach: Twenty male Sprague Dawley rats were randomized and received a sciatic-femoral neurectomy (SFN), Botox-induced muscle paralysis of the proximal femur muscles, quadriceps femoris, hamstrings, and calf muscles (BTX), or sham. Muscle force was measured 52 days postsurgery, and samples were collected for histology, protein, and mRNA assays. Results: SFN and BTX decreased twitch and tetanic force, decreased fiber size by twofold, and increased myogenic expression compared with controls. SFN increased the levels of all major extracellular matrix proteins correlating with fibrosis [e.g., laminin, fibronectin, and collagen type(s) I, III, VI]. SFN also increased profibrotic and proinflammatory mRNA compared with BTX and controls. Innovation: SFN and BTX were similar in gross morphology and functional deficiencies. However, SFN exhibited a higher amount of fibrosis in histological sections and immunoblotting. The present study shows evidence that nerve signaling changes NF-κB and TGF-β signaling, warranting future studies to determine the mechanisms involved. Conclusion: These data indicate that nerve signaling may influence fibrogenesis following denervation, but the mechanisms involved may differ as a function of the method of paralysis.

Muscle Quality as a Potential Diagnostic Marker of Advanced Liver Fibrosis in Patients with Non-alcoholic Fatty Liver Disease.

Muscle-liver crosstalk plays an important role in the development and progression of non-alcoholic fatty liver disease (NAFLD). The measurement of muscle echo-intensity during ultrasonography is a real-time, non-invasive method of assessing muscle quality. In this retrospective study, we investigated the significance of poor muscle quality (namely, a greater mass of non-contractile tissue, including intramuscular fat) as a risk factor for advanced liver fibrosis and considered whether it may represent a useful tool for the diagnosis of advanced liver fibrosis. We analyzed data from 307 patients with NAFLD (143 men and 164 women) who visited the University of Tsukuba Hospital between 2017 and 2022. The patients were stratified into the following tertiles of muscle quality according to their muscle echo-intensity on ultrasonography: modest (84.1 arbitrary units [A.U.]), intermediate (97.4 A.U.), and poor (113.6 A.U.). We then investigated the relationships between muscle quality and risk factors for advanced liver fibrosis and calculated appropriate cutoff values. Patients with poor muscle quality showed a significant, 7.6-fold greater risk of liver fibrosis compared to those with modest muscle quality. Receiver operating characteristic curve analysis showed that muscle quality assessment was as accurate as the fibrosis-4 index and NAFLD fibrosis score in screening for liver fibrosis and superior to the assessment of muscle quantity and strength, respectively. Importantly, a muscle echo-intensity of ≥92.4 A.U. may represent a useful marker of advanced liver fibrosis. Muscle quality may represent a useful means of identifying advanced liver fibrosis, and its assessment may become a useful screening tool in daily practice.

Injectable Self-Oxygenating Cardio-Protective and Tissue Adhesive Silk-Based Hydrogel for Alleviating Ischemia After Mi Injury.

Myocardial infarction (MI) is a significant cardiovascular disease that restricts blood flow, resulting in massive cell death and leading to stiff and noncontractile fibrotic scar tissue formation. Recently, sustained oxygen release in the MI area has shown regeneration ability; however, improving its therapeutic efficiency for regenerative medicine remains challenging. Here, a combinatorial strategy for cardiac repair by developing cardioprotective and oxygenating hybrid hydrogels that locally sustain the release of stromal cell-derived factor-1 alpha (SDF) and oxygen for simultaneous activation of neovascularization at the infarct area is presented. A sustained release of oxygen and SDF from injectable, mechanically robust, and tissue-adhesive silk-based hybrid hydrogels is achieved. Enhanced endothelialization under normoxia and anoxia is observed. Furthermore, there is a marked improvement in vascularization that leads to an increment in cardiomyocyte survival by ≈30% and a reduction of the fibrotic scar formation in an MI animal rodent model. Improved left ventricular systolic and diastolic functions by ≈10% and 20%, respectively, with a ≈25% higher ejection fraction on day 7 are also observed. Therefore, local delivery of therapeutic oxygenating and cardioprotective hydrogels demonstrates beneficial effects on cardiac functional recovery for reparative therapy.

Regulation of cardiac fibroblasts reprogramming into cardiomyocyte-like cells with a cocktail of small molecule compounds.

Myocardial infarction results in extensive cardiomyocyte apoptosis, leading to the formation of noncontractile scar tissue. Given the limited regenerative capacity of adult mammalian cardiomyocytes, direct reprogramming of cardiac fibroblasts (CFs) into cardiomyocytes represents a promising therapeutic strategy for myocardial repair, and small molecule drugs might offer a more attractive alternative to gene editing approaches in terms of safety and clinical feasibility. This study aimed to reprogram rat CFs into cardiomyocytes using a small molecular chemical mixture comprising CHIR99021, Valproic acid, Dorsomorphin, SB431542, and Forskolin. Immunofluorescence analysis revealed a significant increase in the expression of cardiomyocyte-specific markers, including cardiac troponin T (cTnT), Connexin 43 (Cx43), α-actinin, and Tbx5. Changes in intracellular calcium ion levels and Ca2+ signal transfer between adjacent cells were monitored using a calcium ion fluorescence probe. mRNA sequencing analysis demonstrated the upregulation of genes associated with cardiac morphogenesis, myocardial differentiation, and muscle fiber contraction during CF differentiation induced by the small-molecule compounds. Conversely, the expression of fibroblast-related genes was downregulated. These findings suggest that chemical-induced cell fate conversion of rat CFs into cardiomyocyte-like cells is feasible, offering a potential therapeutic solution for myocardial injury.

Comparison of the masses and amounts of intramuscular non-contractile tissue of the lower extremity muscles, mobility and balance ability, and cognitive function between older adults with and without low back pain: A pilot study

IntroductionThis study compared the masses and amounts of intramuscular non-contractile tissue of multiple lower extremity muscles measured using an ultrasound imaging device, as well as the mobility and balance ability and cognitive function between community-dwelling older adults with and without low back pain (LBP). MethodsTwenty-five community-dwelling older adults were classified into control (CTR) (n = 17, asymptomatic) and LBP (n = 8) groups. The current LBP status in the LBP group was as follows: duration period: 99.4 ± 81.3 months, Numerical Rating Scale: 4.8 ± 0.9, and Oswestry Disability Index: 15.3 ± 10.4%. The thicknesses and the echo intensities of various muscles (gluteus maximus, medius, and minimus; rectus femoris; vastus intermedius and lateralis; long and short heads of the biceps femoris; semitendinosus; semimembranosus; tibialis anterior; medial head of the gastrocnemius; soleus; and tibialis posterior) were measured using an ultrasound imaging device. Mobility and balance ability were assessed by measuring the usual and maximal walking speeds, timed up-and-go time, five-chair-stand time, and one-legged stance time. Mini-Mental State Examination scores were also assessed. ResultsThe gluteus medius muscle thickness was significantly lower in the LBP group than in the CTR group. The thicknesses and echo intensities of the other lower extremity muscles did not differ significantly between the CTR and LBP groups. The usual walking speed was also significantly slower in the LBP group than in the CTR group. Balance ability and cognitive function did not differ significantly between the two groups. ConclusionThe results of the present study demonstrated lower gluteus medius muscle mass and slower usual walking speed in community-dwelling older adults with LBP compared to those in older adults without LBP; however, other variables did not differ significantly between these groups.

Quadriceps composition and function influence downhill gait biomechanics >1 year following anterior cruciate ligament reconstruction

BackgroundQuadriceps dysfunction is common following anterior cruciate ligament reconstruction and contributes to aberrant gait biomechanics. Changes in quadriceps composition also occur in these patients including greater concentrations of non-contractile tissue. The purpose of this study was to evaluate associations between quadriceps composition, function, and gait biomechanics in individuals with anterior cruciate ligament reconstruction. MethodsForty-eight volunteers with anterior cruciate ligament reconstruction completed gait biomechanics and quadriceps function and composition assessments. Gait biomechanics were sampled during downhill walking (−10° slope) on an instrumented treadmill. Quadriceps function (peak torque and rate of torque development) was assessed via maximal isometric contractions, while composition was evaluated via ultrasound echo intensity. FindingsGreater quadriceps peak torque was associated with a greater peak knee extension moment (r = 0.365, p = 0.015). Greater vastus lateralis echo intensity (i.e. poorer muscle quality) was associated with less knee flexion displacement (r = −0.316, p = 0.032). Greater echo intensity of the vastus lateralis (r = −0.298, p = 0.044) and rectus femoris (r = −0.322, p = 0.029) was associated with a more abducted knee angle at heel strike. Quadriceps peak torque explained 11–16% of the variance in echo intensity. InterpretationBoth quadriceps function and composition influence aberrant gait biomechanics following anterior cruciate ligament reconstruction. Quadriceps composition appears to provide insight into quadriceps dysfunction independent of muscle strength, as they associated with different gait biomechanics outcomes and shared minimal variance. Future research is necessary to determine the influence of changes in quadriceps composition on joint health outcomes.

Mitochondrial Melatonin: Beneficial Effects in Protecting against Heart Failure.

Cardiovascular disease is the cause of physical infirmity and thousands of deaths annually. Typically, during heart failure, cardiomyocyte mitochondria falter in terms of energy production and metabolic processing. Additionally, inflammation and the accumulation of non-contractile fibrous tissue contribute to cardiac malfunction. Melatonin, an endogenously produced molecule, experimentally reduces the initiation and progression of atherosclerotic lesions, which are often the basis of coronary artery disease. The current review critically analyzes published data related to the experimental use of melatonin to forestall coronary artery pathologies. Collectively, these studies document melatonin's anti-atherosclerotic actions in reducing LDL oxidation and triglyceride levels, lowering endothelial malfunction, limiting adhesion molecule formation, preventing macrophage polarization to the M1 pro-inflammatory phenotype, changing cellular metabolism, scavenging destructive reactive oxygen species, preventing the proliferation and invasion of arterial smooth muscle cells into the lesioned area, restricting the ingrowth of blood vessels from the vasa vasorum, and solidifying the plaque cap to reduce the chance of its rupture. Diabetic hyperglycemia, which aggravates atherosclerotic plaque formation, is also inhibited by melatonin supplementation in experimental animals. The potential value of non-toxic melatonin as a possible inhibitor of cardiac pathology in humans should be seriously considered by performing clinical trials using this multifunctional molecule.

Longitudinal Changes in Quadriceps Morphology over the First 3 Months after Anterior Cruciate Ligament Reconstruction.

Neuromuscular deficits and atrophy after anterior cruciate ligament reconstruction (ACLR) may be accompanied by changes in muscle composition and poor quadriceps muscle quality (QMQ). Quadriceps atrophy occurs after ACLR but improves within the first three postoperative months, yet this hypertrophy could be attributable to increases in noncontractile tissue (i.e., poor QMQ). The purposes of this study were to evaluate changes in QMQ after ACLR and to determine if changes in QMQ and cross-sectional area (CSA) occur in parallel or independently. A longitudinal prospective cohort design was implemented to evaluate QMQ and CSA in 20 individuals with ACLR and 12 healthy controls. Participants completed three testing sessions (baseline/presurgery, 1 month, and 3 months) during which ultrasound images were obtained from the vastus lateralis (VL) and rectus femoris (RF). QMQ was calculated as the echo intensity (EI) of each image, with high EI representing poorer QMQ. Anatomical CSA was also obtained from each image. RF and VL EI were greater at 1 and 3 months in the ACLR limb compared with baseline and the contralateral limb and did not change between 1 and 3 months. VL and RF CSA in the ACLR limb were smaller at 1 and 3 months compared with the contralateral limb and controls (VL only) but increased from 1 to 3 months. Changes in QMQ and CSA were not correlated. QMQ declines within the first month after ACLR and does not improve by 3 months although hypertrophy occurs, suggesting that these morphological characteristics change independently after ACLR. Poorer QMQ represents greater concentration of noncontractile tissues within the muscle and potentially contributes to chronic quadriceps dysfunction observed after ACLR.

Wnt signaling regulates ion channel expression to promote smooth muscle and cartilage formation in developing mouse trachea.

Ion channels play critical roles in the physiology and function of the nervous system and contractile tissue; however, their role in noncontractile tissue and embryonic development has yet to be understood. Tracheobronchomalacia (TBM) and complete tracheal rings (CTR) are disorders affecting the muscle and cartilage of the trachea and bronchi, whose etiology remains poorly understood. We demonstrated that trachealis muscle organization and polarity are disrupted after epithelial ablation of Wntless (Wls), a cargo receptor critical for the Wnt signaling pathway, in developing trachea. The phenotype resembles the anomalous trachealis muscle observed after deletion of ion channel encoding genes in developing mouse trachea. We sought to investigate whether and how the deletion of Wls affects ion channels during tracheal development. We hypothesize that Wnt signaling influences the expression of ion channels to promote trachealis muscle cell assembly and patterning. Deleting Wls in developing trachea causes differential regulation of genes mediating actin binding, cytoskeleton organization, and potassium ion channel activity. Wnt signaling regulates the expression of Kcnj13, Kcnd3, Kcnj8, and Abcc9 as demonstrated by in vitro studies and in vivo analysis in Wnt5a and β-catenin-deficient tracheas. Pharmacological inhibition of potassium ion channels and Wnt signaling impaired contractility of developing trachealis smooth muscle and formation of cartilaginous mesenchymal condensation. Thus, in mice, epithelial-induced Wnt/β-catenin signaling mediates trachealis muscle and cartilage development via modulation of ion channel expression, promoting trachealis muscle architecture, contractility, and cartilaginous extracellular matrix. In turn, ion channel activity may influence tracheal morphogenesis underlying TBM and CTR.NEW & NOTEWORTHY Ion channels play critical roles in the physiology and function of the nervous system and contractile tissue; however, their role in noncontractile tissue and embryonic development has yet to be understood. In this study, we focused on the role of ion channels in the differentiation and patterning of the large airways of the developing respiratory tract. We identify a mechanism by which Wnt-beta-catenin signaling controls levels of ion channel-encoding genes to promote tracheal differentiation.

Association of activities of daily living, mobility and balance ability, and symptoms of Parkinson's disease with the masses and amounts of intramuscular non-contractile tissue of the trunk and lower extremity muscles in patients with Parkinson's disease.

We examined the association of activities of daily living (ADL), mobility and balance ability, and symptoms of Parkinson's disease (PD) with the masses and amounts of intramuscular non-contractile tissue of the trunk and lower extremity muscles in patients with PD. The subjects were 11 community-dwelling patients with PD. ADL were assessed using the Functional Independence Measure. Mobility capacity was assessed based on measurement of maximal walking speed and timed up-and-go time, while balance ability was evaluated based on measurement of one-legged stance time. The symptoms of PD were assessed based on measurement of the Hoehn and Yahr stage and Unified Parkinson's Disease Rating Scale. Muscle thickness (MT) and echo intensity (EI) of the trunk and lower extremity muscles were also measured using an ultrasound imaging device. Partial correlation analysis revealed an association between reduced ADL and increased EI of the lumbar erector spinae muscle; reduced mobility capacity and increased EI of the rectus abdominis and gluteus minimus muscles; and reduced balance ability and decreased MT of the lumbar erector spinae muscle and increased EI of the lumbar erector spinae, semitendinosus, and tibialis posterior muscles. Partial correlation analysis also showed an association between symptoms of severe PD and decreased MT of the tibialis anterior muscles and increased EI of the lumbar erector spinae, gluteus minimus, and tibialis posterior muscles. The properties of the trunk and lower extremity muscles may be critical for ADL, mobility and balance ability, and symptoms of PD in patients with PD.

Reconstruction of soft noncontractile tissue in the derived therizinosaur Nothronychus: The interplay of soft tissue and stress on hindlimb ossification and posture.

Nothronychus graffami was a large therizinosaur from the Upper Cretaceous of North America. Much of the skeleton is well-preserved and relatively undistorted. The synovial capsule, extracapsular, and intracapsular tendons are reconstructed in N. graffami using existing scars and comparison with the hips of extant theropods and models of extinct theropods. The iliofemoral, pubofemoral, and ischiofemoral ligaments are all modeled. Soft tissue, especially the ischiofemoral and pubofemoral ligaments reduced possible protraction/retraction of the femur at the hip while stabilizing the joint. Therefore, most hindlimb movements took place at the knee. Weight-bearing function in Nothronychus was transferred from the supra-acetabular crest to the pubic peduncle and associated labrum at rest. The femur possessed an intermediately angled neck, convergent with titanosaurs. Therefore, some lateral abduction is proposed, requiring a well-developed meniscus at the knee. Such a posture would result in considerable mediolateral stress along the femoral shaft, resulting in increased transverse ossification. The femur is considered somewhat abducted from the midline, especially when maximally pronated, as the preacetabular ala is more extensive than the post-acetabular ala. This trait would probably result in a laterally divergent femur, as in many birds, resulting in a broad-gauge trackway with wider separation between left and right footprints than observed in many theropod trackways. Limb ratios and ossification patterns suggest a slow, waddling gait. A standard digitiform pose is reconstructed as is common for theropods, but a plantigrade stance cannot be firmly rejected.

Muscle disuse as hindlimb unloading in early postnatal mice negatively impacts grip strength in adult mice: a pilot study.

Physical inactivity has many detrimental effects on health, yet the impact of physical inactivity in early life on muscle health in adulthood remains unknown. Early postnatal malnutrition has prolonged effects into adulthood and we propose that early postnatal (P) physical inactivity would have similar negative effects. To test this hypothesis, we exposed postnatal mice (∼P28, C57BL/6J) to 14 days of physical inactivity (shortly after weaning, from ∼P28 to P42 days of age) in the form of muscle disuse with hindlimb unloading (HU). After this early-life physical inactivity, they were allowed to normally ambulate until 5 mo of age (P140, adulthood) when they underwent 14 days of HU with and without 7-day recovery. They were then tested for physical function (grip strength) and muscles were extracted and weighed. Immunofluorescence was carried out on these muscle cross sections for analysis of myofiber cross-sectional area (fCSA), macrophage density (CD68+ cells), and extracellular matrix (ECM) area. Muscle weights and fCSA and myofiber diameter were used to quantify changes in muscle and fiber size. Compared with age-matched controls, no notable effects of early-life physical inactivity (HU) on skeletal muscle and myofiber size were observed. However, a significant reduction in adult grip strength was observed in those exposed to HU early in life. This was associated with reduced muscle macrophages and increased ECM area. Exposure to a short period of early life disuse has negative enduring effects into adulthood impacting grip strength, muscle macrophages, and muscle composition as low muscle quality.NEW & NOTEWORTHY We demonstrate that early life disuse resulted in less grip strength in adulthood. Analysis of muscle composition demonstrated no loss of whole muscle or myofiber size indicating lower muscle quality akin to premature aging. This poor muscle quality was characterized by altered muscle macrophages and extracellular matrix area. We demonstrate intriguing correlations between this loss of grip strength and muscle macrophages and also area of noncontractile tissue in the muscle.

Mitochondria transplant therapy improves regeneration and restoration of injured skeletal muscle.

Injection of exogenous mitochondria has been shown to improve the ischaemia-damaged myocardium, but the effect of mitochondrial transplant therapy (MTT) to restore skeletal muscle mass and function has not been tested following neuromuscular injury. Therefore, we tested the hypothesis that MTT would improve the restoration of muscle function after injury. BaCl2 was injected into the gastrocnemius muscle of one limb of 8-12-week-old C57BL/6 mice to induce damage without injury to the resident stem cells. The contralateral gastrocnemius muscle was injected with phosphate-buffered saline (PBS) and served as the non-injured intra-animal control. Mitochondria were isolated from donor mice. Donor mitochondria were suspended in PBS or PBS without mitochondria (sham treatment) and injected into the tail vein of BaCl2 injured mice 24h after the initial injury. Muscle repair was examined 7, 14 and 21days after injury. MTT did not increase systemic inflammation in mice. Muscle mass 7days following injury was 21.9±2.1% and 17.4±1.9% lower (P<0.05) in injured as compared with non-injured intra-animal control muscles in phosphate-buffered saline (PBS)- and MTT-treated animals, respectively. Maximal plantar flexor muscle force was significantly lower in injured as compared with uninjured muscles of PBS-treated (-43.4±4.2%, P<0.05) and MTT-treated mice (-47.7±7.3%, P<0.05), but the reduction in force was not different between the experimental groups. The percentage of collagen and other non-contractile tissue in histological muscle cross sections, was significantly greater in injured muscles of PBS-treated mice (33.2±0.2%) compared with MTT-treated mice (26.5±0.2%) 7days after injury. Muscle wet weight and maximal muscle force from injured MTT-treated mice had recovered to control levels by 14days after the injury. However, muscle mass and force had not improved in PBS-treated animals by 14days after injury. The non-contractile composition of the gastrocnemius muscle tissue cross sections was not different between control, repaired PBS-treated and repaired MTT-treated mice 14days after injury. By 21days following injury, PBS-treated mice had fully restored gastrocnemius muscle mass of the injured muscle to that of the uninjured muscle, although maximal plantar flexion force was still 19.4±3.7% (P<0.05) lower in injured/repaired gastrocnemius as compared with uninjured intra-animal control muscles. Our results suggest that systemic mitochondria delivery can enhance the rate of muscle regeneration and restoration of muscle function following injury.

Association of sagittal spinal alignment in the standing position with the masses and amounts of intramuscular non-contractile tissue of the trunk and lower extremity muscles in patients with Parkinson's disease

BackgroundWe examined the association of sagittal spinal alignment in the standing position with the masses and amounts of intramuscular non-contractile tissue of multiple trunk and lower extremity muscles, such as the hip joint muscles, measured using an ultrasound imaging device in patients with Parkinson's disease (PD). MethodsThe participants were 10 patients with PD. Sagittal spinal alignment (thoracic kyphosis, lumbar lordosis, and sacral anterior inclination angles) in the standing position was measured using a Spinal Mouse. Muscle thicknesses and echo intensities of the trunk and lower extremity muscles, including the hip joint muscles, were also measured in the prone or supine position using an ultrasound imaging device. FindingsPartial correlation analysis with body height and weight as control variables showed that a low lumbar lordosis angle in the standing position was significantly associated with low thicknesses of the trunk extensor muscles (lumbar erector spinae and multifidus). Partial correlation analysis also revealed that a high sacral anterior inclination angle in the standing position was significantly associated with low lumbar multifidus muscle thickness. However, the thicknesses and echo intensities of the trunk flexor and hip joint muscles were not significantly related to thoracic kyphosis, lumbar lordosis, or sacral anterior inclination angles. InterpretationThe results of this study suggested the association between a low lumbar lordosis angle in the standing position and low lumbar erector spinae and multifidus muscle thicknesses and between a high sacral anterior inclination angle in the standing position and low lumbar multifidus muscle thickness in patients with PD.

Greater hip abductor size in prearthritic patients with developmental dysplasia of the hip versusfemoroacetabular impingement.

Developmental dysplasia of the hip (DDH) and femoroacetabular impingement (FAI) are common hip pathologies and important risk factors for osteoarthritis, yet the disease mechanisms differ. DDH involves deficient femoral head coverage and a shortened abductor moment arm, so this study hypothesized that the cross-sectional area (CSA) of the gluteus medius/minimus muscle complex and the stabilizing iliocapsularis muscle would be larger in DDH versus FAI, without increased fatty infiltration. A longitudinal cohort identified prearthritic patients with DDH or FAI who underwent imaging before surgery. Patients with DDH and FAI (Cam, Pincer, or Mixed) were 1:1 matched based on age, sex, and body mass index. Magnetic resonance imaging was used to measure the gluteus medius/minimus complex and iliocapsularis in two transverse planes. Amira software was used to quantify muscle and noncontractile tissue. Paired samples t-tests were performed to compare muscle size and composition (p < 0.05). There were no differences in the iliocapsularis muscle. Patients with DDH had significantly larger CSA of the gluteus medius/minimus complex at both transverse planes, and the noncontractile tissue proportion did not differ. The mean difference in overall muscle CSA at the anterior inferior iliac spine was 4.07 ± 7.4 cm2 (p = 0.005), with an average difference of 12.1%, and at the femoral head this was 2.40 ± 4.37 cm2 (p = 0.004), with an average difference of 20.2%. This study reports a larger CSA of the gluteus medius/minimus muscle complex in DDH compared to FAI, without a difference in noncontractile tissue, indicating increased healthy muscle in DDH.

Muscle weakness is associated with non-contractile muscle tissue of the vastus medialis muscle in knee osteoarthritis

BackgroundQuadriceps weakness is assumed to be associated with compositional properties of the vastus medialis muscle in patients with knee osteoarthritis (OA).MethodsThe aim was to determine the association of non-contractile muscle tissue in the vastus medialis muscle, measured with routine MRI, with muscle extensor strength in patients with knee OA. Sagittal T1-weighted 3T MRI of 94 patients with knee OA, routinely acquired in clinical practice were used for analysis. Using the MRI’s, the amount of non-contractile muscle tissue in the vastus medialis muscle was measured, expressed as a percentage of (non)-contractile tissue, dichotomized into a low and a high non-contractile percentage group. Muscle strength was assessed by isokinetic measurement of knee extensors and by conduction of the Get-Up and Go (GUG) test. In regression analyses, associations of percentage of non-contractile muscle tissue with muscle strength and GUG time were determined and controlled for sex, age, BMI and radiographic severity.ResultsA high percentage of non-contractile muscle tissue (> 11.2%) was associated with lower muscle strength (B = -0.25, P = 0.006) and with longer GUG time (B = 1.09, P = 0.021). These associations were specifically confounded by sex and BMI, because these two variables decreased the regression coefficient (B) with > 10%.ConclusionsA high percentage of non-contractile muscle tissue in the vastus medialis muscle measured by clinical T1-weighted 3T MRI is associated with muscle weakness. The association is confounded by sex and BMI. Non-contractile muscle tissue seems to be an important compositional property of the vastus medialis muscle underlying quadriceps weakness.

Comparison of the mass and amount of intramuscular non-contractile tissue of the trunk and lower extremity muscles between patients with Parkinson's disease and community-dwelling older adults.

This study compared the masses and amounts of intramuscular non-contractile tissue of the trunk and lower extremity muscles, sagittal spinal alignment, and mobility and balance ability between patients with Parkinson's disease (PD) and older adults. This study included 26 older adults (control [CTR] group) and eight patients with PD (PD group). Muscle thicknesses and echo intensities of the trunk and lower extremity muscles were measured using an ultrasound imaging device. Sagittal spinal alignments in the standing and prone positions were assessed using a Spinal Mouse. Mobility capacity was assessed based on the measurements of usual and maximal walking speeds, timed up-and-go (TUG) time, and five-chair-stand time, while balance ability was assessed based on the measurement of one-legged stance (OLS) time. Our results showed significantly lower gluteus maximus and tibialis anterior muscle thicknesses, higher thickness of the short head of the biceps femoris muscle, and higher echo intensity of the gluteus maximus muscle in the PD group than in the CTR group. Lumbar lordosis angle in the standing position, usual and maximal walking speeds, and OLS time were significantly lower, while the TUG and five-chair-stand times were significantly higher in the PD group than in the CTR group. The other factors did not differ significantly between groups. Our results revealed lower masses of the gluteus maximus and tibialis anterior muscles, higher mass of the short head of the biceps femoris muscle, and higher amounts of intramuscular non-contractile tissue of the gluteus maximus muscle in patients with PD.

Nutrition assistance improves skeletal muscle function and performance in community-dwelling older women

Objective: To analyze the effects of nutritional assistance focusing on protein intake (in the individual’s usual diet) in relation to muscle mass, and the muscle strength and functional performance of community-dwelling older women. Methods: This is a non-randomized controlled clinical trial. Forty-three community-dwelling older women, who were allocated to the Control Group (CG; n = 20) or the Nutrition Group (NG; n = 23). The NG received individualized nutrition assistance and participated in group activities that focused on dietary protein intake once a week for 12 weeks. Main outcome measures: protein and energy intake; handgrip strength (HGS); gait speed (GS); quadriceps cross-sectional area (CSA); and intramuscular non-contractile tissue (IMNCT). The Student’s t-test for independent samples, the Mann-Whitney U test, and a mixed model ANOVA with two factors (group and time) were adopted, followed by a post hoc Bonferroni test. A Spearman’s correlation test was performed on tests for HGS; GS; CSA; IMNCT; age; and protein intake adjusted for weight (g/kg) (p ≤ 0.050). Results: Participants in the NG showed higher CSA values than those in the CG (p &lt; 0.001). NG participants also had higher HGS (p &lt; 0.001) and GS (p = 0.037) when compared to pre-intervention. Correlations were observed between IMNCT and protein intake adjusted for weight (g/kg) (r = -0.517; p = 0.020); HGS, and CSA (r = 0.827; p = 0.000); and CSA and age (r = -0.520, p = 0.009). Conclusions: A nutrition assistance program focusing on protein intake resulted in enhanced muscle function and physical performance.

Association of mobility capacity with the masses and amounts of intramuscular non-contractile tissue of the trunk and lower extremity muscles in community-dwelling older adults.

We examined the association of mobility capacity with muscle thicknesses and echo intensities of the trunk and lower extremity muscles measured using an ultrasound imaging device in community-dwelling older adults. The participants were 57 community-dwelling older adults. Mobility capacity was assessed based on the measurement of usual and maximal walking speeds and timed up-and-go (TUG) time. Muscle thickness and echo intensity of the trunk and lower extremity muscles were measured using an ultrasound imaging device. Finally, sagittal spinal alignment was assessed based on the measurement of thoracic kyphosis, lumbar lordosis, and sacral anterior inclination angles in the standing position using a Spinal Mouse. Stepwise regression analysis showed that the tibialis anterior muscle thickness, tibialis posterior muscle echo intensity, and body weight were significant and independent factors of usual walking speed, with a coefficient of determination (R2) of 0.25. The thicknesses of the thoracic erector spinae and obliquus externus abdominis muscles were significant and independent factors of maximal walking speed (R2=0.26). Moreover, only age was a significant and independent factor for TUG time (R2=0.10). The results of this study suggested associations 1) between slow usual walking speed and low tibialis anterior muscle thicknesses and high echo intensity of the tibialis posterior muscle and 2) between slow maximal walking speed and low thoracic erector spinae and obliquus externus abdominis thicknesses in community-dwelling older adults.