A critical examination of the maximum velocity of shortening used in simulation models of human movement

The maximum velocity of shortening of a muscle is an important parameter in musculoskeletal models. The most commonly used values are derived from animal studies; however, these values are well above the values that have been reported for human muscle. The purpose of this study was to examine the sensitivity of simulations of maximum vertical jumping performance to the parameters describing the force–velocity properties of muscle. Simulations performed with parameters derived from animal studies were similar to measured jump heights from previous experimental studies. While simulations performed with parameters derived from human muscle were much lower than previously measured jump heights. If current measurements of maximum shortening velocity in human muscle are correct, a compensating error must exist. Of the possible compensating errors that could produce this discrepancy, it was concluded that reduced muscle fibre excursion is the most likely candidate.     

The influence of an elastic tendon on the force producing capabilities of a muscle during dynamic movements

With increasing computer power, computer simulation of human movement has become a popular research tool. However, time to complete simulations can still be long even on powerful computers. One possibility for reducing simulation time, with models of musculo-skeletal system, is to simulate the muscle using a rigid tendon rather than the more realistic compliant tendon. This study examines the effect of tendon elasticity on muscle force output under different dynamic conditions. A single muscle, point mass model was used and simulations were performed varying the mass, the tendon length, the initial position, and the task. For simulations for relatively slow motion, as experienced for example in upper limb reaching motions or rising from a chair, tendon properties had little influence on muscle force, in contrast simulations of an explosive task similar to jumping or throwing tendon had a much larger effect.     

Heterogeneous fascicle behavior within the biceps femoris long head at different muscle activation levels

Magnetic resonance and ultrasound imaging have shown hamstring strain injuries occur most often in the biceps femoris long head (BFLH), and particularly in the proximal vs. distal region of this muscle. Animal research and musculoskeletal modeling (MSK) have detected heterogeneous fascicle behavior within muscle regions, and within fascicles. Understanding architectural behavior differences during muscle contractions may help to discern possible mechanisms behind proximal BFLH injuries. The purpose of our study was to assess the magnitude of shortening of the proximal and distal fascicles of the BFLH under a range of muscle activation levels under isometric conditions using ultrasound imaging (US). Thirteen healthy adults performed targeted sustained isometric contractions while US were taken of the entire BFLH. Measurements of fascicle lengths in both muscle regions were compared at 20%, 30%, 50%, and 67% MVIC. The results showed that while both regions shortened significantly with activation, the proximal fascicles were significantly longer, regardless of activation level (~38%), and shortened significantly more than the distal fascicles overall (~40%), and cumulatively at higher activation levels (30% and above). No significant strain differences were found between the two regions. These data suggest heterogeneous fascicle behavior exists in an absolute sense; however, differences in behavior are eliminated when normalized (strain). Coupled with MSK literature, the absence of regional fascicle strain differences in this study may indicate strain heterogeneity is not detectable at the whole fascicle level. Further knowledge of this commonly strained muscle?s regional behavior during dynamic movements could provide evidence of proximal hamstring strain predisposition.     

Mild autonomic dysfunction in primary Sj?gren's syndrome: a controlled study

Introduction  

The aim of this study was to compare cardiovascular autonomic nervous system function in patients with primary Sj?gren's syndrome (pSS) with that in control individuals, and to correlate the findings with autonomic symptoms and the presence of exocrine secretory dysfunction.     

Aberrant Splicing in Transgenes Containing Introns,Exons, and V5 Epitopes: Lessons from Developing an FSHD Mouse Model Expressing a D4Z4 Repeat with Flanking Genomic Sequences

The DUX4 gene, encoded within D4Z4 repeats on human chromosome 4q35, has recently emerged as a key factor in the pathogenic mechanisms underlying Facioscapulohumeral muscular dystrophy (FSHD). This recognition prompted development of animal models expressing the DUX4 open reading frame (ORF) alone or embedded within D4Z4 repeats. In the first published model, we used adeno-associated viral vectors (AAV) and strong viral control elements (CMV promoter, SV40 poly A) to demonstrate that the DUX4 cDNA caused dose-dependent toxicity in mouse muscles. As a follow-up, we designed a second generation of DUX4-expressing AAV vectors to more faithfully genocopy the FSHD-permissive D4Z4 repeat region located at 4q35. This new vector (called AAV.D4Z4.V5.pLAM) contained the D4Z4/DUX4 promoter region, a V5 epitope-tagged DUX4 ORF, and the natural 3’ untranslated region (pLAM) harboring two small introns, DUX4 exons 2 and 3, and the non-canonical poly A signal required for stabilizing DUX4 mRNA in FSHD. AAV.D4Z4.V5.pLAM failed to recapitulate the robust pathology of our first generation vectors following delivery to mouse muscle. We found that the DUX4.V5 junction sequence created an unexpected splice donor in the pre-mRNA that was preferentially utilized to remove the V5 coding sequence and DUX4 stop codon, yielding non-functional DUX4 protein with 55 additional residues on its carboxyl-terminus. Importantly, we further found that aberrant splicing could occur in any expression construct containing a functional splice acceptor and sequences resembling minimal splice donors. Our findings represent an interesting case study with respect to AAV.D4Z4.V5.pLAM, but more broadly serve as a note of caution for designing constructs containing V5 epitope tags and/or transgenes with downstream introns and exons.     

An examination of possible quadriceps force at the time of anterior cruciate ligament injury during landing: A simulation study

Anterior cruciate ligament (ACL) rupture is a common and traumatic injury. Although, identifying the mechanism of ACL injury has received considerable research attention, there are still many unanswered questions. One proposed mechanism asserts that the ACL is injured due to an aggressive quadriceps muscle contraction. However, recently it has been questioned if the magnitude of quadriceps force needed to tear the ACL is physiologically realistic under the conditions where injury occurs during landing (e.g. near full knee extension and within 50ms after impact). To answer this question, a simple simulation model was developed to examine the upper bounds of quadriceps force that can be developed under these conditions. The model included force-length, and force-velocity properties as well as activation dynamics. Model parameters were chosen to provide a high estimate for possible quadriceps force in a young healthy man. The effects of varying quadriceps pre-activation levels were also examined. When using realistic pre-activation levels, the simulated quadriceps force was less than half of what has been shown to cause ACL injury. Even when using maximum pre-activation, the quadriceps force still did not reach close to the level shown to cause injury. Therefore, we conclude that quadriceps force alone seems to be an unlikely mechanism for ACL injury.     

The influence of an elastic tendon on the force producing capabilities of a muscle during dynamic movements

With increasing computer power, computer simulation of human movement has become a popular research tool. However, time to complete simulations can still be long even on powerful computers. One possibility for reducing simulation time, with models of musculo-skeletal system, is to simulate the muscle using a rigid tendon rather than the more realistic compliant tendon. This study examines the effect of tendon elasticity on muscle force output under different dynamic conditions. A single muscle, point mass model was used and simulations were performed varying the mass, the tendon length, the initial position, and the task. For simulations for relatively slow motion, as experienced for example in upper limb reaching motions or rising from a chair, tendon properties had little influence on muscle force, in contrast simulations of an explosive task similar to jumping or throwing tendon had a much larger effect.     

Wave attenuation as a measure of muscle quality as measured by magnetic resonance elastography: Initial results

Advances in imaging technologies such as magnetic resonance elastography (MRE) have allowed researchers to gain insights into muscle function in vivo. MRE has been used to examine healthy and diseased muscle by calculating shear modulus. However, additional information can be measured from visualizing a mechanical wave as it passes through a tissue. One such measurable quantity is wave attenuation. The purpose of this study was to determine if a simple measure of wave attenuation could be used to distinguish between healthy and diseased muscle. Twenty seven subjects (14 healthy controls, 7 hyperthyroid myopathy patients, 6 myositis patients) participated in this study. Wave amplitude was determined along a linear profile through the center of the muscle, and an exponential decay curve was fit to the data. This measure was able to find significant differences in attenuation between healthy and diseased muscle. Furthermore, four hyperthyroid myopathy subjects who were tested following treatment all showed improvement by this measure. A likely reason for patients with hyperthyroid myopathy and myositis behaving similarly is that this measurement may reflect similar changes in the muscle extracellular matrix. In addition to modulus, attenuation seems to be an important parameter to measure in skeletal muscle. Further research is needed to investigate other potential measures of attenuation as well as examining other potential measures that can be found from visualizing wave propagation. Future studies should also include muscle biopsies to confirm that the changes seen are as a result of changes in extracellular matrix structure.