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Introduction: Patients with peripheral arterial disease (PAD) develop a myopathy in their ischemic limbs which is characterized by myofiber degeneration, mitochondrial dysfunction and decreased muscle force production. Desmin, a cytoskeletal protein of the myofiber, is central to maintenance of the structure, shape and function of the myofiber and its organelles especially the mitochondria. Hypothesis: We hypothesized that desmin expression in myofibers of the gastrocnemius of PAD patients is abnormal and correlates with decreased mitochondrial respiration and reduced muscle strength. Methods and Results: We quantified desmin protein and gene transcripts in myofibers of gastrocnemius biopsies from 30 PAD patients and 29 controls and determined their association with myofiber morphology, mitochondrial respiration and calf muscle strength. Compared to control, desmin protein and gene transcripts were increased in myofibers of PAD gastrocnemius. Increased expression was associated with a diffuse appearance of the protein, suggesting a loss of its normally filamentous structure. These changes in desmin correlated with altered myofiber morphology, decreased mitochondrial respiration and reduced calf muscle strength. Conclusions: Desmin expression and organization are abnormal in myofibers of the gastrocnemius of patients with PAD and these changes correlate with decreased mitochondrial function and reduced muscle strength.

Background Peripheral arterial disease ( PAD ) is characterized by myofiber degeneration and loss of function in muscles of the lower limbs. Human enterovirus ( HEV ) infection has been implicated in the pathogenesis of a number of muscle diseases. However, its association with PAD has not been studied. In this study, we tested the hypothesis that infectious HEV is present in skeletal muscle of patients with PAD and is associated with severity of disease. Methods and Results Gastrocnemius biopsies from 37 patients with PAD and 14 controls were examined for the presence of HEV RNA , viral capsid protein, viral RNA copy number, and viral infectivity. HEV RNA was detected in 54% of the biopsies from patients with PAD but was not detected in muscle biopsies from control patients. This difference in prevalence among PAD and control patients was significant at P RNA copy numbers were increased significantly at the later stages of disease; Fontaine Stage IV (10 5.50 copies/mg muscle wet weight, at P 4.87 copies/mg, at P 2.50 copies/mg). Viral replication was confirmed by the presence of the negative‐strand of viral RNA in all specimens positive for HEV RNA . Cultures of HeLa and human skeletal muscle cells treated with muscle homogenates showed HEV replication and the presence of HEV capsid protein. Conclusion Our data identified infectious HEV in the gastrocnemius of PAD patients but not in controls. Viral copy number and prevalence of infection were higher in the later stages of disease. Our data point to the need for further studies to determine the contribution of HEV infection to the pathophysiology of PAD .

Peripheral arterial disease (PAD), which affects ∼10 million Americans, is characterized by atherosclerosis of the noncoronary arteries. PAD produces a progressive accumulation of ischemic injury to the legs, manifested as a gradual degradation of gastrocnemius histology. In this study, we evaluated the hypothesis that quantitative morphological parameters of gastrocnemius myofibers change in a consistent manner during the progression of PAD, provide an objective grading of muscle degeneration in the ischemic limb, and correlate to a clinical stage of PAD. Biopsies were collected with a Bergström needle from PAD patients with claudication ( n = 18) and critical limb ischemia (CLI; n = 19) and control patients ( n = 19). Myofiber sarcolemmas and myosin heavy chains were labeled for fluorescence detection and quantitative analysis of morphometric variables, including area, roundness, perimeter, equivalent diameter, major and minor axes, solidity, and fiber density. The muscle specimens were separated into training and validation data sets for development of a discriminant model for categorizing muscle samples on the basis of disease severity. The parameters for this model included standard deviation of roundness, standard deviation of solidity of myofibers, and fiber density. For the validation data set, the discriminant model accurately identified control (80.0% accuracy), claudicating (77.7% accuracy), and CLI (88.8% accuracy) patients, with an overall classification accuracy of 82.1%. Myofiber morphometry provided a discriminant model that establishes a correlation between PAD progression and advancing muscle degeneration. This model effectively separated PAD and control patients and provided a grading of muscle degeneration within clinical stages of PAD.

It was suggested that baseline levels of postural control in figure skaters might influence the effectiveness of neuromuscular training. The aims of the present study were to investigate the baseline association of skater skill level with standard center of pressure metrics and time to stabilization, and to determine if skill level influenced the effectiveness of a 6-week neuromuscular training program. There was no main effect of skill level for any baseline center of pressure metric for either test. There was no main effect of skill level on the percent change in any metric for the single leg stance following training. However, skill level did influence landing test outcome measures. The difference in percent change of root mean squared was evident for the mediolateral (low: 24.5±16.50% vs. high: 2.42±14.99%) and anterior-posterior (low: 6.66±9.21% vs. high: − 4.03±5.91%) axes. Percent change in anterior-posterior time to stabilization also differed by skill level (low: − 0.73%±4.74 vs. high: − 5.61%±2.76). Note that this study was underpowered with 26 subjects and 14 subjects contributing to baseline and post-training assessments, respectively. Though no baseline differences in postural control were observed, compared with low skill levels, high skill levels benefitted more from training.

Path integration refers to the ability to integrate continuous information of the direction and distance travelled by the system relative to the origin. Previous studies have investigated path integration through blindfolded walking along simple paths such as straight line and triangles. However, limited knowledge exists regarding the role of path complexity in path integration. Moreover, little is known about how information from different sensory input systems (like vision and proprioception) contributes to accurate path integration. The purpose of the current study was to investigate how sensory information and curved path complexity affect path integration. Forty blindfolded participants had to accurately reproduce a curved path and return to the origin. They were divided into four groups that differed in the curved path, circle (simple) or figure-eight (complex), and received either visual (previously seen) or proprioceptive (previously guided) information about the path before they reproduced it. The dependent variables used were average trajectory error, walking speed, and distance travelled. The results indicated that (a) both groups that walked on a circular path and both groups that received visual information produced greater accuracy in reproducing the path. Moreover, the performance of the group that received proprioceptive information and later walked on a figure-eight path was less accurate than their corresponding circular group. The groups that had the visual information also walked faster compared to the group that had proprioceptive information. Results of the current study highlight the roles of different sensory inputs while performing blindfolded walking for path integration.

Learning to control forces is known to reduce the amount of movement variability (e.g., standard deviation; SD) while also altering the temporal structure of movement variability (e.g., approximate entropy; ApEn). Such variability control has not been explored in stroke survivors during reaching movements in dynamic environments. Whether augmented feedback affects such variability control, is also unknown. Chronic stroke survivors, assigned randomly to a control/experimental group, learned reaching movements in a dynamically changing environment while receiving either true feedback of their movement (control) or augmented visual feedback (experimental). Hand movement variability was analyzed using SD and ApEn. A significant change in variability was determined for both SD and ApEn. Post hoc tests revealed that the significant decrease in SD was not retained after a week. However, the significant increase in ApEn, determined on both days of training, showed significant retention effects. In dynamically changing environments, chronic stroke survivors reduced the amount of movement variability and made their movement patterns less repeatable and possibly more flexible. These changes were not affected by augmented visual feedback. Moreover, the learning patterns characteristically involved the control of the nonlinear dynamics rather than the amount of hand movement variability. The absence of transfer effects demonstrated that variability control of hand movement after a stroke is specific to the task and the environment.

Peripheral arterial disease (PAD) is characterized by atherosclerotic blockages of the arteries supplying the lower extremities, which cause a progressive accumulation of ischemic injury to the skeletal muscles of the lower limbs. This injury includes altered metabolic processes, damaged organelles, and compromised bioenergetics in the affected muscles. The objective of this study was to explore the association of Raman spectral signatures of muscle biochemistry with the severity of atherosclerosis in the legs as determined by the Ankle Brachial Index (ABI) and clinical presentation. We collected muscle biopsies from the gastrocnemius (calf muscle) of five patients with clinically diagnosed claudication, five patients with clinically diagnosed critical limb ischemia (CLI), and five control patients who did not have PAD. A partial least squares regression (PLSR) model was able to predict patient ABI with a correlation coefficient of 0.99 during training and a correlation coefficient of 0.85 using a full cross‐validation. When using the first three PLS factor scores in combination with linear discriminant analysis, the discriminant model was able to correctly classify the control, claudicating, and CLI patients with 100% accuracy, using a full cross‐validation procedure. Raman spectroscopy is capable of detecting and measuring unique biochemical signatures of skeletal muscle. These signatures can discriminate control muscles from PAD muscles and correlate with the ABI and clinical presentation of the PAD patient. Raman spectroscopy provides novel spectral biomarkers that may complement existing methods for diagnosis and monitoring treatment of PAD patients., Raman spectroscopy is capable of detecting and measuring unique biochemical signatures of skeletal muscle. These signatures can discriminate control muscles from peripheral arterial disease (PAD) muscles and correlate with the ABI and clinical presentation of the PAD patient. Raman spectroscopy provides novel spectral biomarkers that may complement existing methods for diagnosis and monitoring treatment of PAD patients.

Mortality rates of patients with peripheral arterial disease are predicted by the respiratory activities of gastrocnemius mitochondrial complexes I and IV Jonathan Robert Thompson, MD*, Stanley A Swanson, BS, Gleb Haynatzki, PhD, George P Casale, PhD, Jason M Johanning, MD, FACS, Evlampia Papoutsi, BS, Panagiotis Koutakis, MS, Dimitrios Miserlis, MD, Zhen Zhu, MD, Iraklis I Pipinos, MD, PhD, FACS University of Nebraska Medical Center, Omaha, NE

Peripheral arterial disease (PAD), a manifestation of systemic atherosclerosis that produces blockages in arteries supplying the legs, affects an estimated 27 million people in Europe and North America. Increased production of reactive oxygen species by dysfunctional mitochondria in leg muscles of PAD patients is viewed as a key mechanism of initiation and progression of the disease. Previous studies demonstrated increased oxidative damage in homogenates of biopsy specimens from PAD gastrocnemius compared to controls, but did not address myofiber-specific damage. In this study, we investigated oxidative damage to myofibers as a possible cause of the myopathy of PAD. To achieve this, we developed and validated fluorescence microscopy procedures for quantitative analysis of carbonyl groups and 4-hydroxy-2-nonenal (HNE) adducts in myofibers of biopsy specimens from human gastrocnemius. PAD and control specimens were evaluated for differences in 1) myofiber content of these two forms of oxidative damage and 2) myofiber cross-sectional area. Furthermore, oxidative damage to PAD myofibers was tested for associations with clinical stage of disease, degree of ischemia in the affected leg, and myofiber cross-sectional area. Carbonyl groups and HNE adducts were increased 30% (p