Comparison of Ultrastructural Alterations in Peripheral Artery Disease Skeletal Muscle

Peripheral artery disease (PAD) is characterized by obstructed hemodynamics and claudication reducing quality of life and muscle function. A myopathy has been shown to develop in PAD patients and characterization of changes in skeletal muscle needs further elucidation. PURPOSE: To assess myofibrillar ultrastructural changes between control and stage IV PAD patients. METHODS: Twenty-six participants (13 control:13 stage IV) were recruited to take part in this cross-sectional study. The mean(±SD) age, mass, height, and BMI were 53(±11) years, 81(±22) kg, 165(±15) cm, and 30(±1.5) kg/m2. Muscle samples were collected from the gastrocnemius and prepared for transmission electron microscopy. Relative mitochondria area, average mitochondrial size, number of mitochondria/250μm2, relative myofibril area, average m-line length, number of z-discs/250μm2, mitochondria/z-disc, relative lipid droplet area, average lipid droplet size, and number of lipid droplets/250μm2 were measured and averaged for each participant using two-individual micrographs. All variables were statistically assessed using an independent t-test or Mann-Whitney U at a significance value of pRESULTS:Relative mitochondrial area (U=11.534, p2 (t=5.343, p2 (t=-1.902, p=.07) was observed. M-line lengths were shorter for stage IV PAD patients than controls (U=11.543, p2 (U=.037, p=.848). Average mitochondria/z-disc was significantly greater in controls than in stage IV PAD patients (t=5.737, pCONCLUSION:The largest changes seen in PAD skeletal muscle ultrastructure are in the mitochondria number and total mitochondria area. This decrease in mitochondria may explain altered muscle function not accounted for by hemodynamic obstructions

Abnormal myofiber morphology and limb dysfunction in claudication

Background Peripheral artery disease (PAD), which affects an estimated 27 million people in Europe and North America, is caused by atherosclerotic plaques that limit blood flow to the legs. Chronic, repeated ischemia in the lower leg muscles of PAD patients is associated with loss of normal myofiber morphology and myofiber degradation. In this study, we tested the hypothesis that myofiber morphometrics of PAD calf muscle are significantly different from normal calf muscle and correlate with reduced calf muscle strength and walking performance. Methods Gastrocnemius biopsies were collected from 154 PAD patients (Fontaine stage II) and 85 control subjects. Morphometric parameters of gastrocnemius fibers were determined and evaluated for associations with walking distances and calf muscle strength. Results Compared with control myofibers, PAD myofiber cross-sectional area, major and minor axes, equivalent diameter, perimeter, solidity, and density were significantly decreased (P \u3c 0.005), whereas roundness was significantly increased (P \u3c 0.005). Myofiber morphometric parameters correlated with walking distances and calf muscle strength. Multiple regression analyses demonstrated myofiber cross-sectional area, roundness, and solidity as the best predictors of calf muscle strength and 6-min walking distance, whereas cross-sectional area was the main predictor of maximum walking distance. Conclusions Myofiber morphometrics of PAD gastrocnemius differ significantly from those of control muscle and predict calf muscle strength and walking distances of the PAD patients. Morphometric parameters of gastrocnemius myofibers may serve as objective criteria for diagnosis, staging, and treatment of PAD

Abnormal Accumulation of Desmin in Gastrocnemius Myofibers of Patients with Peripheral Artery Disease: Associations with Altered Myofiber Morphology and Density, Mitochondrial Dysfunction and Impaired Limb Function

Patients with peripheral artery disease (PAD) develop a myopathy in their ischemic lower extremities, which is characterized by myofiber degeneration, mitochondrial dysfunction and impaired limb function. Desmin, a protein of the cytoskeleton, is central to maintenance of the structure, shape and function of the myofiber and its organelles, especially the mitochondria, and to translation of sarcomere contraction into muscle contraction. In this study, we investigated the hypothesis that disruption of the desmin network occurs in gastrocnemius myofibers of PAD patients and correlates with altered myofiber morphology, mitochondrial dysfunction, and impaired limb function. Using fluorescence microscopy, we evaluated desmin organization and quantified myofiber content in the gastrocnemius of PAD and control patients. Desmin was highly disorganized in PAD but not control muscles and myofiber content was increased significantly in PAD compared to control muscles. By qPCR, we found that desmin gene transcripts were increased in the gastrocnemius of PAD patients as compared with control patients. Increased desmin and desmin gene transcripts in PAD muscles correlated with altered myofiber morphology, decreased mitochondrial respiration, reduced calf muscle strength and decreased walking performance. In conclusion, our studies identified disruption of the desmin system in gastrocnemius myofibers as an index of the myopathy and limitation of muscle function in patients with PAD

SYSTEM AND METHOD FOR MONITORING PLEURAL FLUID

The disclosure is directed to intrapleural air leak detection and monitoring. According to various embodiments of the disclosure, an air leak may be detected utilizing at least one sensor to determine whether fluid extracted from a pleural cavity of a patient includes carbon dioxide and/or a second substance. The second substance may be a foreign substance inhaled by the patient to confirm presence of the air leak. The air leak may be further monitored over a period of time by collecting temporally successive measurements associated with detected concentrations of carbon dioxide. Therefore, tissue damage and recovery may be assessed according to objectively collected criteria

Intelligent System Utilizing HOG and CNN for Thermal Image-Based Detection of Wild Animals in Nocturnal Periods for Vehicle Safety

Animal Vehicle Collision, commonly called roadkill, is an emerging threat to drivers and wild animals, increasing fatalities every year. Currently, prevalent methods using visible light cameras are efficient for animal detection in daylight time. This paper focuses on locating wildlife close to roads during nocturnal hours by utilizing thermographic obtained images, thus enhancing vehicle safety. In particular, it proposes an intelligent system for animal detection during nighttime that combines the technique of Histogram of Oriented Gradients (HOG) with a Convolutional Neural Network (CNN). The proposed intelligent system is benchmarked against a variety of CNN’s like basic CNN and VGG16-based CNN and also with the machine learning algorithms such as Support Vector Machine (SVM), Random Forest (RF), Decision Tree Algorithm (DT), Linear Regression (LR), and Gaussian Naïve Bayes (GNB). The proposed detection system was tested on a set of real-world data acquired with a thermal camera on the move in the city of San Antonio, TX, USA that includes images of wild deer. Obtained results exhibit that the HOG-CNN combination achieved approximately 91% correct detection accuracy of wild deer on roadsides, while it outperformed the rest of the tested machine learning algorithms

Oxidative damage and myofiber degeneration in the gastrocnemius of patients with peripheral arterial disease

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 \u3c 0.0001) and 40% (p \u3c 0.0001), respectively, in the myofibers of PAD (N = 34) compared to control (N = 21) patients. Mean cross-sectional area of PAD myofibers was reduced 29.3% compared to controls (p \u3c 0.0003). Both forms of oxidative damage increased with clinical stage of disease, blood flow limitation in the ischemic leg, and reduced myofiber cross-sectional area. The data establish oxidative damage to myofibers as a possible cause of PAD myopathy

High-Fat Diet Augments the Effect of Alcohol on Skeletal Muscle Mitochondrial Dysfunction in Mice

Previous studies have shown that chronic heavy alcohol consumption and consumption of a high-fat (HF) diet can independently contribute to skeletal muscle oxidative stress and mitochondrial dysfunction, yet the concurrent effect of these risk factors remains unclear. We aimed to assess the effect of alcohol and different dietary compositions on mitochondrial activity and oxidative stress markers. Male and female mice were randomized to an alcohol (EtOH)-free HF diet, a HF + EtOH diet, or a low-Fat (LF) + EtOH diet for 6 weeks. At the end of the study, electron transport chain complex activity and expression as well as antioxidant activity and expression, were measured in skeletal muscles. Complex I and III activity were diminished in muscles of mice fed a HF + EtOH diet relative to the EtOH-free HF diet. Lipid peroxidation was elevated, and antioxidant activity was diminished, in muscles of mice fed a HF + EtOH diet as well. Consumption of a HF diet may exacerbate the negative effects of alcohol on skeletal muscle mitochondrial health and oxidative stress