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Magnetization transfer (MT) magnetic resonance imaging (MRI) can be used to estimate the fraction of water and macromolecular proton pools in tissues. MT modeling paired with ultrashort echo time acquisition (UTE‐MT modeling) has been proposed to improve the evaluation of the myotendinous junction and fibrosis in muscle tissues, which the latter increases with aging. This study aimed to determine if the UTE‐MT modeling technique is sensitive to age‐related changes in the skeletal muscles of the lower leg. Institutional review board approval was obtained, and all recruited subjects provided written informed consent. The legs of 31 healthy younger (28.1 ± 6.1 years old, BMI = 22.3 ± 3.5) and 20 older (74.7 ± 5.5 years old, BMI = 26.7 ± 5.9) female subjects were imaged using UTE sequences on a 3 T MRI scanner. MT ratio (MTR), macromolecular fraction (MMF), macromolecular T2 (T2‐MM), and water T2 (T2‐W) were calculated using UTE‐MT modeling for the anterior tibialis (ATM), posterior tibialis (PTM), soleus (SM), and combined lateral muscles. Results were compared between groups using the Wilcoxon rank sum test. Three independent observers selected regions of interest (ROIs) and processed UTE‐MRI images separately, and the intraclass correlation coefficient (ICC) was calculated for a reproducibility study. Significantly lower mean MTR and MMF values were present in the older compared with the younger group in all studied lower leg muscles. T2‐MM showed significantly lower values in the older group only for PTM and SM muscles. In contrast, T2‐W showed significantly higher values in the older group. The age‐related differences were more pronounced for MMF (−17 to −19%) and T2‐W (+20 to 47%) measurements in all muscle groups compared with other investigated MR measures. ICCs were higher than 0.93, indicating excellent consistency between the ROI selection and MRI measurements of independent readers. As demonstrated by significant differences between younger and older groups, this research emphasizes the potential of UTE‐MT MRI techniques in evaluating age‐related skeletal muscle changes. [ABSTRACT FROM AUTHOR]

Myofibres serve as the functional unit for locomotion, with the sarcomere as fundamental subunit. Running the entire length of this structure are hundreds of myonuclei, located at the periphery of the myofibre, juxtaposed to the plasma membrane. Myonuclear specialisation and clustering at the centre and ends of the fibre are known to be essential for muscle contraction, yet the molecular basis of this regionalisation has remained unclear. While the 'myonuclear domain hypothesis' helped explain how myonuclei can independently govern large cytoplasmic territories, novel technologies have provided granularity on the diverse transcriptional programs running simultaneously within the syncytia and added a new perspective on how myonuclei communicate. Building upon this, we explore the critical cellular and molecular sources of transcriptional and functional heterogeneity within myofibres, discussing the impact of intrinsic and extrinsic factors on myonuclear programs. This knowledge provides new insights for understanding muscle development, repair, and disease, but also opens avenues for the development of novel and precise therapeutic approaches. [ABSTRACT FROM AUTHOR]

The myotendinous junction (MTJ) is structurally specialized to transmit force. The highly folded muscle membrane at the MTJ increases the contact area between muscle and tendon and potentially the load tolerance of the MTJ. Muscles with a high content of type II fibers are more often subject to strain injury compared with muscles with type I fibers. It is hypothesized that this is explained by a smaller interface area of MTJ in type II compared with type I muscle fibers. The aim was to investigate by confocal microscopy whether there is difference in the surface area at the MTJ between type I and II muscle fibers. Individual muscle fibers with an intact MTJ were isolated by microscopic dissection in samples from human semitendinosus, and they were labeled with antibodies against collagen XXII (indicating MTJ) and type I myosin (MHCI). Using a spinning disc confocal microscope, the MTJ from each fiber was scanned and subsequently reconstructed to a 3D‐model. The interface area between muscle and tendon was calculated in type I and II fibers from these reconstructions. The MTJ was analyzed in 314 muscle fibers. Type I muscle fibers had a 22% larger MTJ interface area compared with type II fibers (p < 0.05), also when the area was normalized to fiber diameter. By the new method, it was possible to analyze the structure of the MTJ from a large number of human muscle fibers. The finding that the interface area between muscle and tendon is higher in type I compared with type II fibers suggests that type II fibers are less resistant to strain and therefore more susceptible to injury. [ABSTRACT FROM AUTHOR]

In the musculoskeletal system, the myotendinous junction (MTJ) is optimally designed from the aspect of force transmission generated from a muscle through a tendon onto the bone to induce movement. Although the MTJ is a key complex tissue in force transmission, the realistic fabrication, and formation of complex tissues can be limited. To obtain the MTJ construct, we prepared two bioinks, muscle‐ and tendon‐derived decellularized extracellular matrix (dECM), which can induce myogenic and tenogenic differentiation of human adipose‐derived stem cells (hASCs). By using a modified bioprinting process supplemented with a nozzle consisting of a single‐core channel and double‐sheath channels, we can achieve three different types of MTJ units, composed of muscle, tendon, and interface zones. Our results indicated that the bioprinted dECM‐based constructs induced hASCs to myogenic and tenogenic differentiation. In addition, a significantly higher MTJ‐associated gene expression was detected at the MTJ interface with a cell‐mixing zone than in the other interface models. Based on the results, the bioprinted MTJ model can be a potential platform for understanding the interaction between muscle and tendon cells, and even the bioprinting method can be extensively applied to obtain complex tissues. [ABSTRACT FROM AUTHOR]

The surgical fixation of an acute on chronic pectoralis major rupture with inciting injury 7 years prior has never been reported in the literature. Thus, we report the first case of an acute on chronic pectoralis major rupture repair in an active male patient who underwent successful surgical intervention and review the pathophysiology and treatment of pectoralis major tears. [ABSTRACT FROM AUTHOR]

The morphology of the more superficial tissue of the human tongue was investigated and discussed with the clinical appearance of fissures. Three regions could be distinguished according to the presence and shape of the aponeurosis linguae: the central region showed a thick aponeurotic plate with myotendinous muscle fibre insertions. The lateral region showed still an aponeurosis linguae but of reduced thickness and without muscle insertions. The edge‐wise and lower region showed no aponeurosis linguae but a fatty subcutis and myocutaneous muscle fibre insertions lacking specific molecules of myotendinous junctions. This system of partially developed exoskeleton seems to underlie but not to be involved in tongue fissures, which are more superficial within the epidermis and dermis. [ABSTRACT FROM AUTHOR]

The present study tested the hypothesis that 30 low‐intensity (10%) eccentric contractions (10%EC) or two maximal voluntary isometric contractions at a long muscle length (2MVIC) that were performed at two days before maximal eccentric exercise of the elbow flexors consisting of five sets of six maximal eccentric contractions (MaxEC) would reduce increases in biceps brachii distal myotendinous junction displacement (MTJd) over the eccentric contractions during MaxEC. Sedentary young men were randomly placed (n = 12/group) to a control group that performed two bouts of MaxEC (CONT‐1st, CONT‐2nd) separated by two weeks, or one of two preconditioning groups that performed 10%EC or 2MVIC at 20° elbow flexion at two days prior to MaxEC. All exercises were performed by the non‐dominant arm. MTJd of each contraction was assessed by B‐mode ultrasound, and its changes over sets were compared among the groups. The average MTJd from the start to the end of six eccentric contractions in the first set was similar among the groups (6.4 ± 0.7 mm). The MTJd increased from the first to fifth set, but the increase was smaller (P <.05) for the 10%EC (13 ± 6%) and 2MVIC (16 ± 9%) groups, and CONT‐2nd (3 ± 6%) when compared with CONT‐1st (60 ± 12%). Both 10%EC and 2MVIC groups showed smaller (P <.05) changes in all muscle damage markers after MaxEC similarly when compared with CONT‐1st, but the changes were greater than those after CONT‐2nd. These results supported the hypothesis that protective effect was associated with less MTJd changes, suggesting that this is associated with the mechanisms underpinning the preconditioning effect on muscle damage. [ABSTRACT FROM AUTHOR]

The myotendinous junction (MTJ) is at high risk of strain injuries, due to high amounts of energy that is transferred through this structure. The risk of strain injury is significantly reduced by heavy resistance training (HRT), indicating a remodeling capacity of MTJ. We investigated the degree of remodeling of muscle fibers near the human MTJ. In 8 individuals, samples were taken from the semitendinosus and gracilis MTJ and they were stained immunohistochemically for myonuclei (DAPI), fibroblasts (TCF7L2), and satellite cells (CD56). A high portion of the muscle fibers adjacent to the MTJ contained a centrally located myonucleus (47 ± 8%, mean ± SD) and half of the muscle fibers were CD56 positive. The number of satellite cells and fibroblasts were not higher than what has previously been reported from muscle bellies. The immunohistochemical findings suggest that the rate of remodeling of muscle fibers near the MTJ is very high. The finding that there was no increased number of satellite cells and fibroblasts could be explained as a dynamic phenomenon. The effect of HRT should be evaluated in a randomized setting. [ABSTRACT FROM AUTHOR]

Displacement of the myotendinous junction (MTJ) obtained by ultrasound imaging is crucial to quantify the interactive length changes of muscles and tendons for understanding the mechanics and pathological conditions of the muscle-tendon unit during motion. However, the lack of a reliable automatic measurement method restricts its application in human motion analysis. This paper presents an automated measurement of MTJ displacement using prior knowledge on tendinous tissues and MTJ, precluding the influence of nontendinous components on the estimation of MTJ displacement. It is based on the perception of tendinous features from musculoskeletal ultrasound images using Radon transform and thresholding methods, with information about the symmetric measures obtained from phase congruency. The displacement of MTJ is achieved by tracking manually marked points on tendinous tissues with the Lucas-Kanade optical flow algorithm applied over the segmented MTJ region. The performance of this method was evaluated on ultrasound images of the gastrocnemius obtained from 10 healthy subjects (26.0±2.9 years of age). Waveform similarity between the manual and automatic measurements was assessed by calculating the overall similarity with the coefficient of multiple correlation (CMC). In vivo experiments demonstrated that MTJ tracking with the proposed method (CMC = 0.97±0.02) was more consistent with the manual measurements than existing optical flow tracking methods (CMC = 0.79±0.11). This study demonstrated that the proposed method was robust to the interference of nontendinous components, resulting in a more reliable measurement of MTJ displacement, which may facilitate further research and applications related to the architectural change of muscles and tendons. [ABSTRACT FROM AUTHOR]

The myotendinous junction ( MTJ) is a common site of strain injury and yet understanding of its composition and ability to adapt to loading is poor. The main aims of this study were to determine the profile of selected collagens and macrophage density in human MTJ and adjoining muscle fibers, and to investigate whether heavy exercise loading would alter this profile. Fifteen individuals scheduled for anterior cruciate ligament repair surgery were randomized into three groups: control, acute or 4 weeks heavy resistance training. MTJ samples were collected from the semitendinosus and gracilis muscles and were sectioned and stained immunohistochemically for collagen types I, III, VI, XII, XIV, XXII, Tenascin-C and CD68. Macrophage density and distribution was evaluated and the amount of each collagen type in muscle and MTJ was graded. Collagen XXII was observed solely at the MTJ, while all other collagens were abundant at the MTJ and in muscle perimysium or endomysium. The endomysial content of collagen XIV, macrophages and Tenascin-C increased following 4 weeks of training. These findings illustrate the heterogeneity of collagen type composition of human MTJ. The increase in collagen XIV following 4 weeks of training may reflect a training-induced protection against strain injuries in this region. [ABSTRACT FROM AUTHOR]

Distal myopathies are a group of clinically and pathologically overlapping muscle diseases that are genetically complex and can represent a diagnostic challenge. Laing early-onset distal myopathy (MPD1) is a form of distal myopathy caused by mutations in the MYH7 gene, which encodes the beta myosin heavy chain protein expressed in type 1 skeletal muscle fibers and cardiac myocytes. Here, we present a case of genetically confirmed MPD1 with a typical clinical presentation but distinctive light microscopic and ultrastructural findings on muscle biopsy. A 39-year-old professional male cellist presented with a bilateral foot drop that developed by age 8; analysis of the family pedigree showed an autosomal dominant pattern of inheritance. The physical exam demonstrated bilateral weakness of ankle dorsiflexors, toe extensors and finger extensors; creatine kinase level was normal. Biopsy of the quadriceps femoris muscle showed predominance and hypotrophy of type 1 fibers, hybrid fibers with co-expression of slow and fast myosin proteins (both in highly atrophic and normal size range), moth-eaten fibers and mini-cores, lack of rimmed vacuoles and rare desmin-positive eosinophilic sarcoplasmic inclusions. In addition to these abnormalities often observed in MPD1, the biopsy demonstrated frequent clefted fibers with complex sarcolemmal invaginations; on ultrastructural examination, these structures closely mimicked myotendinous junctions but were present away from the tendon and were almost exclusively found in type 1 fibers. Sequencing analysis of the MYH7 gene in the index patient and other affected family members demonstrated a previously described heterozygous c.4522_4524delGAG (p.Glu1508del) mutation. This case widens the pathologic spectrum of MPD1 and highlights the pathologic and clinical variability that can accompany the same genetic mutation, suggesting a significant role for modifier genes in MPD1 pathogenesis. [ABSTRACT FROM AUTHOR]

The myotendinous junction (MTJ) is a specialized structure in the musculotendinous system, where force is transmitted from muscle to tendon. Animal models have shown that the MTJ takes form of tendon finger-like processes merging with muscle tissue. The human MTJ is largely unknown and has never been described in three dimensions (3D). The aim of this study was to describe the ultrastructure of the human MTJ and render 3D reconstructions. Fourteen subjects (age 25 ± 3 years) with isolated injury of the anterior cruciate ligament (ACL), scheduled for reconstruction with a semitendinosus/gracilis graft were included. Semitendinosus and gracilis tendons were stripped as grafts for the ACL reconstruction. The MTJ was isolated from the grafts and prepared for transmission electron microscopy (TEM) and focused ion beam/scanning electron microscopy. It was possible to isolate recognizable MTJ tissue from all 14 patients. TEM images displayed similarities to observations in animals: Sarcolemmal evaginations observed as finger-like processes from the tendon and endomysium surrounding the muscle fibers, with myofilaments extending from the final Z-line of the muscle fiber merging with the tendon tissue. The 3D reconstruction revealed that tendon made ridgelike protrusions, which interdigitiated with groove-like indentations in the muscle cell. [ABSTRACT FROM AUTHOR]

The cell specific detection of enzyme activation in response to the physiological contractile load within muscle-tendon-bone unit is essential for understanding of the mechanical forces transmission from muscle cells via tendon to the bone. The hypothesis that the physiological mechanical loading regulates activation of Akt1/PKBalpha at Thr308 and at Ser473 in muscle fibers within muscle-tendon-bone unit was tested using quantitative immunohistochemistry, confocal double fluorescence analysis, and immunoblot analysis. In comparison to the staining intensities in peripheral regions of the muscle fibers, Akt1/PKBalpha was detected with a higher staining intensity in muscle fibers at the myotendinous junction (MTJ) areas. In muscle fibers at the MTJ areas, Akt1/PKBalpha is dually phosphorylated at Thr308 and Ser473. The immunohistochemical results were confirmed by immunoblot analysis. We conclude that contractile load generated by masticatory muscles induces local domain-dependent expression of Akt1/PKBalpha as well as activation by dually phosphorylation at Thr308 and Ser473 in muscle fibers at the MTJ areas within muscle-tendon-bone unit. [ABSTRACT FROM AUTHOR]