Skeletal muscle fibrosis can be a devastating clinical problem that arises from many causes, including primary skeletal muscle tissue diseases, as seen in the muscular dystrophies, or it can be ...secondary to events that include trauma to muscle or brain injury. The cellular source of activated fibroblasts (myofibroblasts) may include resident fibroblasts, adult muscle stem cells, or inflammatory or perivascular cells, depending on the model studied. Even though it is likely that there is no single source for all myofibroblasts, a common mechanism for the production of fibrosis is via the transforming growth factor-β/phosphorylated Smad3 pathway. This pathway and its downstream targets thus provide loci for antifibrotic therapies, as do methods for blocking the transdifferentiation of progenitors into activated fibroblasts. A structural model for the extracellular collagen network of skeletal muscle is needed so that measurements of collagen content, morphology, and gene expression can be related to mechanical properties. Approaches used to study fibrosis in tissues, such as lung, kidney, and liver, need to be applied to studies of skeletal muscle to identify ways to prevent or even cure the devastating maladies of skeletal muscle.
Skeletal muscle design to meet functional demands Lieber, Richard L.; Ward, Samuel R.
Philosophical transactions - Royal Society. Biological sciences,
05/2011, Volume:
366, Issue:
1570
Journal Article
Peer reviewed
Open access
Skeletal muscles are length- and velocity-sensitive force producers, constructed of a vast array of sarcomeres. Muscles come in a variety of sizes and shapes to accomplish a wide variety of tasks. ...How does muscle design match task performance? In this review, we outline muscle's basic properties and strategies that are used to produce movement. Several examples are provided, primarily for human muscles, in which skeletal muscle architecture and moment arms are tailored to a particular performance requirement. In addition, the concept that muscles may have a preferred sarcomere length operating range is also introduced. Taken together, the case is made that muscles can be fine-tuned to perform specific tasks that require actuators with a wide range of properties.
Computer models that estimate the force generation capacity of lower limb muscles have become widely used to simulate the effects of musculoskeletal surgeries and create dynamic simulations of ...movement. Previous lower limb models are based on severely limited data describing limb muscle architecture (i.e., muscle fiber lengths, pennation angles, and physiological cross-sectional areas). Here, we describe a new model of the lower limb based on data that quantifies the muscle architecture of 21 cadavers. The model includes geometric representations of the bones, kinematic descriptions of the joints, and Hill-type models of 44 muscle–tendon compartments. The model allows calculation of muscle–tendon lengths and moment arms over a wide range of body positions. The model also allows detailed examination of the force and moment generation capacities of muscles about the ankle, knee, and hip and is freely available at
www.simtk.org
.
Skeletal muscle architecture is defined as the arrangement of fibers in a muscle and functionally defines performance capacity. Architectural values are used to model muscle-joint behavior and to ...make surgical decisions. The two most extensively used human lower extremity data sets consist of five total specimens of unknown size, gender, and age. Therefore, it is critically important to generate a high-fidelity human lower extremity muscle architecture data set. We disassembled 27 muscles from 21 human lower extremities to characterize muscle fiber length and physiologic cross-sectional area, which define the excursion and force-generating capacities of a muscle. Based on their architectural features, the soleus, gluteus medius, and vastus lateralis are the strongest muscles, whereas the sartorius, gracilis, and semitendinosus have the largest excursion. The plantarflexors, knee extensors, and hip adductors are the strongest muscle groups acting at each joint, whereas the hip adductors and hip extensors have the largest excursion. Contrary to previous assertions, two-joint muscles do not necessarily have longer fibers than single-joint muscles as seen by the similarity of knee flexor and extensor fiber lengths. These high-resolution data will facilitate the development of more accurate musculoskeletal models and challenge existing theories of muscle design; we believe they will aid in surgical decision making.
•A novel predictive control system for commercial building heating ventilation and air-conditioning (HVAC).•Multi-objective optimisation framework simultaneously considers energy, operating cost and ...occupant comfort.•Online occupant comfort feedback helps to fine-tune occupant comfort satisfaction.•Results presented from real-world trials have demonstrated energy improvement between 19 and 32% over existing control strategies.
This paper presents the results from two real-world trials of an optimised supervisory model predictive control (MPC) system for heating, ventilation and air conditioning (HVAC) in commercial buildings. The system learns a model from historical data and uses weather forecasts and a given temperature set-point profile to predict building zone conditions and thermal comfort with the aim of optimising building controls for a number of HVAC zones throughout a day. The multi-objective optimisation minimises running cost and CO2 emissions, subject to operator preferences, while constraining occupant thermal discomfort to an acceptable range to find the best zone temperature set-point schedule for the building. This schedule is then applied to the building by a feedback control loop, which balances the power supplied to each zone for heating, cooling and ventilation.
A complementary online occupant comfort feedback tool was deployed to all occupant computers in the trial office buildings. This tool allows occupants to submit feedback on their thermal comfort and satisfaction at any point in time via electronic surveys, as well as allowing these surveys to be issued to occupants at scheduled times. This feedback fine-tuned the thermal comfort model used to constrain the optimisation, allowing for errors in the comfort model to be compensated. Thermal comfort feedback was also used to measure and compare relative occupant comfort levels with a baseline.
This control system was trialled on two office buildings in Australia, over two winter months and results compared with the performance of the incumbent building management and control system (BMCS). An average energy reduction of 19% and 32% was achieved in the two buildings over 51 and 10 days of operation respectively without substantially affecting measured or modelled occupant thermal satisfaction levels.
Purpose
The purpose of this study was to understand potential baseline transcriptional expression differences in paraspinal skeletal muscle from patients with different underlying lumbar pathologies ...by comparing multifidus gene expression profiles across individuals with either disc herniation, facet arthropathy, or degenerative spondylolisthesis.
Methods
Multifidus biopsies were obtained from patients (
n
= 44) undergoing lumbar surgery for either disc herniation, facet arthropathy, or degenerative spondylolisthesis. Diagnostic categories were based on magnetic resonance images, radiology reports, and intraoperative reports. Gene expression for 42 genes was analysed using qPCR. A one-way analysis of variance was performed for each gene to determine differences in expression across diagnostic groups. Corrections for multiple comparisons across genes (Benjamini–Hochberg) and for between-group post hoc comparisons (Sidak) were applied.
Results
Adipogenic gene (ADIPOQ) expression was higher in the disc herniation group when compared to the facet arthropathy group (
p
= 0.032). Adipogenic gene (PPARD) expression was higher in the degenerative spondylolisthesis group when compared to the disc herniation group (
p
= 0.013), although absolute gene expression levels for all groups was low. Fibrogenic gene (COL3A1) had significantly higher expression in the disc herniation group and facet arthropathy group when compared to the degenerative spondylolisthesis group (
p
< 0.001 and
p
= 0.038, respectively). When adjusted for multiple comparisons, only COL3A1 remained significant (
p
= 0.012).
Conclusion
Individuals with disc herniation and facet arthropathy demonstrate higher COL3A1 gene expression compared to those with degenerative spondylolisthesis. Future research is required to further understand the biological relevance of these transcriptional differences.
A skeletal muscle's peak force production and excursion are based on its architectural properties that are, in turn, determined by its mass, muscle fiber length and physiological cross-sectional area ...(PCSA). In the classic interspecific study of mammalian muscle scaling, it was demonstrated that muscle mass scales positively allometrically with body mass whereas fiber length scales isometrically with body mass, indicating that larger mammals have stronger leg muscles than they would if they were geometrically similar to smaller ones. Although this relationship is highly significant across species, there has never been a detailed intraspecific architectural scaling study. We have thus created a large dataset of 896 muscles across 34 human lower extremities (18 females and 16 males) with a size range including approximately 90% and 70% of the United States population height and mass, respectively, across the range 36-103 years. Our purpose was to quantify the scaling relationships between human muscle architectural properties and body size. We found that human muscles depart greatly from isometric scaling because muscle mass scales with body mass1.3 (larger exponent than isometric scaling of 1.0) and muscle fiber length scales with negative allometry with body mass0.1 (smaller exponent than isometric scaling of 0.33). Based on the known relationship between architecture and function, these results suggest that human muscles place a premium on muscle force production (mass and PCSA) at the expense of muscle excursion (fiber length) with increasing body size, which has implications for understanding human muscle design as well as biomechanical modeling.
Cellular remodeling in rotator cuff muscles following a massive rotator cuff tear is poorly understood. The aim of the current study was to provide histological evidence to elucidate the mode of ...muscle loss in advanced human rotator cuff disease and to assess tissue-level changes in relation to findings on noninvasive imaging.
Rotator cuff muscle biopsy samples were taken from the scapular fossae from 23 consecutive patients undergoing reverse total shoulder arthroplasty in order to evaluate muscle composition in severe rotator cuff disease. Markers of vascularity; inflammation; fat distribution; and muscle atrophy, degeneration, and regeneration were quantified.
The samples primarily consisted of dense, organized connective tissue (48.2% ± 19.1%) and disorganized, loose connective tissue (36.9% ± 15.9%), with substantially smaller fractions of muscle (10.4% ± 22.0%) and fat (6.5% ± 11.6%). Only 25.8% of the biopsy pool contained any muscle fibers at all. Increased inflammatory cell counts (111.3 ± 81.5 macrophages/mm) and increased vascularization (66.6 ± 38.0 vessels/mm) were observed across biopsies. Muscle fiber degeneration was observed in 90.0% ± 15.6% of observable muscle fascicles, and the percentage of centrally nucleated muscle fibers was pathologically elevated (11.3% ± 6.3%). Fat accumulation was noted in both perifascicular (60.7% ± 41.4%) and intrafascicular (42.2% ± 33.6%) spaces, with evidence that lipid may replace contractile elements without altering muscle organization.
Dramatic degeneration and inflammation of the rotator cuff muscles are characteristics of the most chronic and severe rotator cuff disease states, suggesting that muscle loss is more complicated than, and distinct from, the simple atrophy found in less severe cases.
In order to address degenerative muscle loss, alternative therapeutic approaches directed at muscle regeneration must be considered if muscle function is to be restored in late-stage rotator cuff disease.
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