Skeletal muscle myosin heavy chain expression and 3D capillary network changes in streptozotocin-induced diabetic female mice.

It is not well-understood how type 1 diabetes (T1DM) affects skeletal muscle histological phenotype, particularly capillarisation. This study aimed to analyze skeletal muscle myosin heavy chain (MyHC) fibre type changes and 3D capillary network characteristics in experimental T1DM mice. Female C57BL/6J-OlaHsd mice were categorized into streptozotocin (STZ)-induced diabetic (n = 12) and age-matched non-diabetic controls (n =12). The muscle fibre phenotype of the soleus, gluteus maximus, and gastrocnemius muscles were characterized based on the expression of MyHC isoforms, while capillaries of the gluteus maximus were assessed with immunofluorescence staining, confocal laser microscopy and 3D image analysis. STZ-induced diabetic mice exhibited elevated glucose levels, reduced body weight, and prolonged thermal latency, verifying the T1DM phenotype. In both T1DM and non-diabetic mice, the gluteus maximus and gastrocnemius muscles predominantly expressed fast-twitch type 2b fibers, with no significant differences noted. However, the soleus muscle in non-diabetic mice had a greater proportion of type 2a fibers and comparable type 1 fiber densities (26.2 ± 14.6% vs 21.9 ± 13.5%) relative to diabetic mice. T1DM mice showed reduced fiber diameters (P = 0.026), and the 3D capillary network analysis indicated a higher capillary length per muscle volume in the gluteus maximus of diabetic mice compared to controls (P < 0.05). Overall, T1DM induced significant changes in the skeletal muscle, including shifts in MyHC fibre types, decreased fibre diameters, and increased relative capillarisation, possibly due to muscle fibre atrophy. Our findings emphasize the superior detail provided by the 3D analytical method for characterizing skeletal muscle capillary architecture, highlighting caution in interpreting 2D data for capillary changes in T1DM.

Application of Virtual Reality Systems in Bone Trauma Procedures.

Background and Objectives: Bone fractures contribute significantly to the global disease and disability burden and are associated with a high and escalating incidence and tremendous economic consequences. The increasingly challenging climate of orthopaedic training and practice re-echoes the established potential of leveraging computer-based reality technologies to support patient-specific simulations for procedural teaching and surgical precision. Unfortunately, despite the recognised potential of virtual reality technologies in orthopaedic surgery, its adoption and integration, particularly in fracture procedures, have lagged behind other surgical specialities. We aimed to review the available virtual reality systems adapted for orthopaedic trauma procedures. Materials and Methods: We performed an extensive literature search in Medline (PubMed), Science Direct, SpringerLink, and Google Scholar and presented a narrative synthesis of the state of the art on virtual reality systems for bone trauma procedures. Results: We categorised existing simulation modalities into those for fracture fixation techniques, drilling procedures, and prosthetic design and implantation and described the important technical features, as well as their clinical validity and applications. Conclusions: Over the past decade, an increasing number of high- and low-fidelity virtual reality systems for bone trauma procedures have been introduced, demonstrating important benefits with regard to improving procedural teaching and learning, preoperative planning and rehearsal, intraoperative precision and efficiency, and postoperative outcomes. However, further technical developments in line with industry benchmarks and metrics are needed in addition to more standardised and rigorous clinical validation.

Exploration of macromolecular phenotype of human skeletal muscle in diabetes using infrared spectroscopy.

Introduction: The global burden of diabetes mellitus is escalating, and more efficient investigative strategies are needed for a deeper understanding of underlying pathophysiological mechanisms. The crucial role of skeletal muscle in carbohydrate and lipid metabolism makes it one of the most susceptible tissues to diabetes-related metabolic disorders. In tissue studies, conventional histochemical methods have several technical limitations and have been shown to inadequately characterise the biomolecular phenotype of skeletal muscle to provide a holistic view of the pathologically altered proportions of macromolecular constituents. Materials and methods: In this pilot study, we examined the composition of five different human skeletal muscles from male donors diagnosed with type 2 diabetes and non-diabetic controls. We analysed the lipid, glycogen, and collagen content in the muscles in a traditional manner with histochemical assays using different staining techniques. This served as a reference for comparison with the unconventional analysis of tissue composition using Fourier-transform infrared spectroscopy as an alternative methodological approach. Results: A thorough chemometric post-processing of the infrared spectra using a multi-stage spectral decomposition allowed the simultaneous identification of various compositional details from a vibrational spectrum measured in a single experiment. We obtained multifaceted information about the proportions of the different macromolecular constituents of skeletal muscle, which even allowed us to distinguish protein constituents with different structural properties. The most important methodological steps for a comprehensive insight into muscle composition have thus been set and parameters identified that can be used for the comparison between healthy and diabetic muscles. Conclusion: We have established a methodological framework based on vibrational spectroscopy for the detailed macromolecular analysis of human skeletal muscle that can effectively complement or may even serve as an alternative to histochemical assays. As this is a pilot study with relatively small sample sets, we remain cautious at this stage in drawing definitive conclusions about diabetes-related changes in skeletal muscle composition. However, the main focus and contribution of our work has been to provide an alternative, simple and efficient approach for this purpose. We are confident that we have achieved this goal and have brought our methodology to a level from which it can be successfully transferred to a large-scale study that allows the effects of diabetes on skeletal muscle composition and the interrelationships between the macromolecular tissue alterations due to diabetes to be investigated.

Pathophysiological and Therapeutic Roles of Fascial Hyaluronan in Obesity-Related Myofascial Disease.

Myofascial disease is an important complication associated with obesity and one of the leading causes of physical disability globally. In the face of limited treatment options, the burden of myofascial disorders is predicted to increase along with the escalating prevalence of obesity. Several pathological processes in obesity contribute to modifications in fascial extracellular matrix mechanical and biological properties and functions. Changes in adipose tissue metabolism, chronic inflammatory phenotype, oxidative stress, and other mechanisms in obesity may alter the physiochemical and biomechanical properties of fascial hyaluronan. Understanding the pathophysiological importance of hyaluronan and other components of the fascial connective tissue matrix in obesity may shed light on the etiology of associated myofascial disorders and inform treatment strategies. Given its unique and favorable pharmacological properties, hyaluronan has found a broad range of clinical applications, notably in orthopedic conditions such as osteoarthritis and tendinopathies, which share important pathophysiological mechanisms implicated in myofascial diseases. However, while existing clinical studies uniformly affirm the therapeutic value of hyaluronan in myofascial disorders, more extensive studies in broader pharmacological and clinical contexts are needed to firmly validate its therapeutic adaptation.

Application of FTIR Spectroscopy to Detect Changes in Skeletal Muscle Composition Due to Obesity with Insulin Resistance and STZ-Induced Diabetes.

Age, obesity, and diabetes mellitus are pathophysiologically interconnected factors that significantly contribute to the global burden of non-communicable diseases. These metabolic conditions are associated with impaired insulin function, which disrupts the metabolism of carbohydrates, lipids, and proteins and can lead to structural and functional changes in skeletal muscle. Therefore, the alterations in the macromolecular composition of skeletal muscle may provide an indication of the underlying mechanisms of insulin-related disorders. The aim of this study was to investigate the potential of Fourier transform infrared (FTIR) spectroscopy to reveal the changes in macromolecular composition in weight-bearing and non-weight-bearing muscles of old, obese, insulin-resistant, and young streptozotocin (STZ)-induced diabetic mice. The efficiency of FTIR spectroscopy was evaluated by comparison with the results of gold-standard histochemical techniques. The differences in biomolecular phenotypes and the alterations in muscle composition in relation to their functional properties observed from FTIR spectra suggest that FTIR spectroscopy can detect most of the changes observed in muscle tissue by histochemical analyses and more. Therefore, it could be used as an effective alternative because it allows for the complete characterization of macromolecular composition in a single, relatively simple experiment, avoiding some obvious drawbacks of histochemical methods.

The Influence of Diabetic Peripheral Neuropathy on the Duration of Sciatic Nerve Block with 1.3% Liposomal Bupivacaine and 0.25% Bupivacaine Hydrochloride in a Mouse Model.

Little is known regarding the pharmacological properties of extended-release local anesthetics in the setting of diabetic peripheral neuropathy. We investigated and compared the duration of sciatic nerve block following administration of clinically relevant concentrations of liposomal bupivacaine (LB) and bupivacaine hydrochloride (BH) in diabetic mice with peripheral neuropathy. In this prospective, randomized, and double-blind study, twenty-four female C57BL/6J-OlaHsd mice were assigned to a streptozotocin-induced type 1 diabetes group and a control group without diabetes. The presence of peripheral neuropathy was established by assessing the duration of thermal latency of the plantar and tail-flick tests, following which both groups were subdivided into two subgroups in which 35 mg/kg of 1.31% LB and 7 mg/kg of 0.25% BH were respectively administered for sciatic nerve block. The average sensory block duration with BH was 106 min and 117.1 min in the control and diabetic groups, respectively. With LB, the average sensory block duration was 118 min in the control mice, while in mice with diabetic peripheral neuropathy, the average block duration was significantly longer and above the 270 min limit set in our study. Accordingly, sensory block duration was longer with LB compared to BH, and diabetic peripheral neuropathy significantly increased sciatic nerve block duration with LB.

Skeletal Muscle Microvascular Dysfunction in Obesity-Related Insulin Resistance: Pathophysiological Mechanisms and Therapeutic Perspectives.

Obesity is a worrisomely escalating public health problem globally and one of the leading causes of morbidity and mortality from noncommunicable disease. The epidemiological link between obesity and a broad spectrum of cardiometabolic disorders has been well documented; however, the underlying pathophysiological mechanisms are only partially understood, and effective treatment options remain scarce. Given its critical role in glucose metabolism, skeletal muscle has increasingly become a focus of attention in understanding the mechanisms of impaired insulin function in obesity and the associated metabolic sequelae. We examined the current evidence on the relationship between microvascular dysfunction and insulin resistance in obesity. A growing body of evidence suggest an intimate and reciprocal relationship between skeletal muscle microvascular and glucometabolic physiology. The obesity phenotype is characterized by structural and functional changes in the skeletal muscle microcirculation which contribute to insulin dysfunction and disturbed glucose homeostasis. Several interconnected etiologic molecular mechanisms have been suggested, including endothelial dysfunction by several factors, extracellular matrix remodelling, and induction of oxidative stress and the immunoinflammatory phenotype. We further correlated currently available pharmacological agents that have deductive therapeutic relevance to the explored pathophysiological mechanisms, highlighting a potential clinical perspective in obesity treatment.