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.

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.

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.

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.

Background/Objectives: Obesity and type 2 diabetes mellitus (T2DM) profoundly disrupt lipid metabolism within local microenvironments of skeletal muscle and its associated connective tissues, including adipose tissue, bone, and fascia. However, the role of local communication between skeletal muscle and its proximal connective tissues in propagating metabolic dysfunction is incompletely understood. This narrative review synthesizes current evidence on these local metabolic interactions, highlighting novel insights and existing gaps. Methods: We conducted a comprehensive literature analysis of primary research published in the last decade, sourced from PubMed, Web of Science, and ScienceDirect. Studies were selected for relevance to skeletal muscle, adipose tissue, fascia, and bone lipid metabolism in the context of obesity and T2DM, with emphasis on molecular, cellular, and paracrine mechanisms of local crosstalk. Findings were organized into thematic sections addressing physiological regulation, pathological remodeling, and inter-organ signaling pathways. Results: Our synthesis reveals that local lipid dysregulation in obesity and T2DM involves altered fatty acid transporter dynamics, mitochondrial overload, fibro-adipogenic remodeling, and compartment-specific adipose tissue dysfunction. Crosstalk via myokines, adipokines, osteokines, bioactive lipids, and exosomal miRNAs integrates metabolic responses across these tissues, amplifying insulin resistance and lipotoxic stress. Emerging evidence highlights the underappreciated roles of fascia and marrow adipocytes in regional lipid handling. Conclusions: Collectively, these insights underscore the pivotal role of inter-tissue crosstalk among skeletal muscle, adipose tissue, bone, and fascia in orchestrating lipid-induced insulin resistance, and highlight the need for integrative strategies that target this multicompartmental network to mitigate metabolic dysfunction in obesity and T2DM.

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.