Dietary fat promotes pathological insulin resistance through chronic inflammation. The inactivation of inflammatory proteins produced by macrophages improves diet-induced diabetes, but how ...nutrient-dense diets induce diabetes is unknown. Membrane lipids affect the innate immune response, which requires domains that influence high-fat-diet-induced chronic inflammation and alter cell function based on phospholipid composition. Endogenous fatty acid synthesis, mediated by fatty acid synthase (FAS), affects membrane composition. Here we show that macrophage FAS is indispensable for diet-induced inflammation. Deleting Fasn in macrophages prevents diet-induced insulin resistance, recruitment of macrophages to adipose tissue and chronic inflammation in mice. We found that FAS deficiency alters membrane order and composition, impairing the retention of plasma membrane cholesterol and disrupting Rho GTPase trafficking-a process required for cell adhesion, migration and activation. Expression of a constitutively active Rho GTPase, however, restored inflammatory signalling. Exogenous palmitate was partitioned to different pools from endogenous lipids and did not rescue inflammatory signalling. However, exogenous cholesterol, as well as other planar sterols, did rescue signalling, with cholesterol restoring FAS-induced perturbations in membrane order. Our results show that the production of endogenous fat in macrophages is necessary for the development of exogenous-fat-induced insulin resistance through the creation of a receptive environment at the plasma membrane for the assembly of cholesterol-dependent signalling networks.
Background
Meniscal ramp lesions have been defined as longitudinal vertical peripheral tears of the medial meniscus involving the posterior meniscocapsular ligament, meniscotibial ligament, and/or ...the red-red zone of the posterior horn. They are heavily associated with anterior cruciate ligament injuries, and because of their potentially important biomechanical role in knee stabilization, injuries to this region may require surgical repair. However, due to their location and lack of general knowledge regarding their different types and associated appearances on magnetic resonance imaging, ramp lesions are routinely underreported. This is compounded by the fact that ramp lesions are also often overlooked during conventional anterior portal arthroscopy when direct visualization is not achieved.
Purpose
To demonstrate MRI appearances and arthroscopic findings of the different types of meniscal ramp lesions, in the hopes of improving their detection on pre-operative imaging.
The rapid advancement of artificial intelligence (AI), particularly the development of Large Language Models (LLMs) such as Generative Pretrained Transformers (GPTs), has revolutionized numerous ...fields. The purpose of this study is to investigate the application of LLMs within the realm of orthopaedic in training examinations.
Questions from the 2020–2022 Orthopaedic In-Service Training Exams (OITEs) were given to OpenAI's GPT-3.5 Turbo and GPT-4 LLMs, using a zero-shot inference approach. Each model was given a multiple-choice question, without prior exposure to similar queries, and their generated responses were compared to the correct answer within each OITE. The models were evaluated on overall accuracy, performance on questions with and without media, and performance on first- and higher-order questions.
The GPT-4 model outperformed the GPT-3.5 Turbo model across all years and question categories (2022: 67.63% vs. 50.24%; 2021: 58.69% vs. 47.42%; 2020: 59.53% vs. 46.51%). Both models showcased better performance with questions devoid of associated media, with GPT-4 attaining accuracies of 68.80%, 65.14%, and 68.22% for 2022, 2021, and 2020, respectively. GPT-4 outscored GPT-3.5 Turbo on first-order questions across all years (2022: 63.83% vs. 38.30%; 2021: 57.45% vs. 50.00%; 2020: 65.74% vs. 53.70%). GPT-4 also outscored GPT-3.5 Turbo on higher-order questions across all years (2022: 68.75% vs. 53.75%; 2021: 59.66% vs. 45.38%; 2020: 53.27% vs. 39.25%).
GPT-4 showed improved performance compared to GPT-3.5 Turbo in all tested categories. The results reflect the potential and limitations of AI in orthopaedics. GPT-4's performance is comparable to a second-to-third-year resident and GPT-3.5 Turbo's performance is comparable to a first-year resident, suggesting the application of current LLMs can neither pass the OITE nor substitute orthopaedic training. This study sets a precedent for future endeavors integrating GPT models into orthopaedic education and underlines the necessity for specialized training of these models for specific medical domains.
Traumatic spinal cord injury (SCI) is associated with a lifetime of disability stemming from loss of motor, sensory, and autonomic functions; these losses, along with increased comorbid sequelae, ...negatively impact health outcomes and quality of life. Early decompression surgery post-SCI can enhance patient outcomes, but does not directly facilitate neural repair and regeneration. Currently, there are no U.S. Food and Drug Administration-approved pharmacological therapies to augment motor function and functional recovery in individuals with traumatic SCI. After an SCI, the enzyme, Rho, is activated by growth-inhibitory factors and regulates events that culminate in collapse of the neuronal growth cone, failure of axonal regeneration, and, ultimately, failure of motor and functional recovery. Inhibition of Rho activation is a potential treatment for injuries such as traumatic SCI. VX-210, an investigational agent, inhibits Rho. When administered extradurally after decompression (corpectomy or laminectomy) and stabilization surgery in a phase 1/2a study, VX-210 was well tolerated. Here, we describe the design of the SPRING trial, a multicenter, phase 2b/3, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of VX-210 (NCT02669849). A subset of patients with acute traumatic cervical SCI is currently being enrolled in the United States and Canada. Medical, neurological, and functional changes are evaluated at 6 weeks and at 3, 6, and 12 months after VX-210 administration. Efficacy will be assessed by the primary outcome measure, change in upper extremity motor score at 6 months post-treatment, and by secondary outcomes that include question-based and task-based evaluations of functional recovery.
Osteoarthritis (OA) is the most common cause of disability worldwide among the elderly. Alarmingly, the incidence of OA in individuals less than 40 years of age is rising, likely due to the increase ...in obesity and post-traumatic osteoarthritis (PTOA). In recent years, due to a better understanding of the underlying pathophysiology of OA, several potential therapeutic approaches targeting specific molecular pathways have been identified. In particular, the role of inflammation and the immune system has been increasingly recognized as important in a variety of musculoskeletal diseases, including OA. Similarly, higher levels of host cellular senescence, characterized by cessation of cell division and the secretion of a senescence-associated secretory phenotype (SASP) within the local tissue microenvironments, have also been linked to OA and its progression. New advances in the field, including stem cell therapies and senolytics, are emerging with the goal of slowing disease progression. Mesenchymal stem/stromal cells (MSCs) are a subset of multipotent adult stem cells that have demonstrated the potential to modulate unchecked inflammation, reverse fibrosis, attenuate pain, and potentially treat patients with OA. Numerous studies have demonstrated the potential of MSC extracellular vesicles (EVs) as cell-free treatments that comply with FDA regulations. EVs, including exosomes and microvesicles, are released by numerous cell types and are increasingly recognized as playing a critical role in cell-cell communication in age-related diseases, including OA. Treatment strategies for OA are being developed that target senescent cells and the paracrine and autocrine secretions of SASP. This article highlights the encouraging potential for MSC or MSC-derived products alone or in combination with senolytics to control patient symptoms and potentially mitigate the progression of OA. We will also explore the application of genomic principles to the study of OA and the potential for the discovery of OA phenotypes that can motivate more precise patient-driven treatments.
Background:
Meniscal injuries are among the most common orthopaedic injuries, with a significant volume of published literature.
Purpose:
To perform a comprehensive bibliometric analysis that ...appropriately evaluates the 50 most cited articles in meniscal research.
Study Design:
Cross-sectional study.
Methods:
We performed a keyword search of the ISI Web of Knowledge database and then pared the results down to the 50 most cited articles using specific inclusion and exclusion criteria. Data extracted included title, first author, citation count, year of publication, topic, journal, article type, country of origin, and level of evidence. Correlation coefficients were calculated between publication date and citation density and between publication date and raw citation count.
Results:
The 50 most cited articles were published from 1975 to 2013. The mean number of citations was 258.24 (range, 163-926; median, 225). The majority of articles were published in The American Journal of Sports Medicine (19%), the Journal of Bone and Joint Surgery (12%), and Arthritis & Rheumatology (14%). Most articles focused on either the anatomy and biomechanics of meniscal injury or on prevention and physical rehabilitation (12 papers each).
Conclusion:
The most popular fields of meniscal research involved anatomy/biomechanics and prevention/rehabilitation, and both are areas that will likely increase the probability of an article’s being highly cited in the future. This study provided a quality selection of the most cited articles on meniscal injury and may provide a foundation for both beginner and senior clinician readers for further discussion and research.
Orthopedic specialties have begun to embrace telehealth as an alternative to in-person visits. We have not found studies assessing telehealth in sports medicine. Our goal is to evaluate patient ...perception of telehealth in an orthopedic sports medicine practice.
Institutional review board (IRB) approval was obtained. The first 100 patients 18 years and older who had their initial videoconference telehealth appointment with our sports medicine providers from March to April 2020 were contacted at the conclusion of their visit. Surveys assessed satisfaction with telehealth, the provider, and whether attire played a role in their perception of the quality of the telehealth visit.
Patients on average stated excellent satisfaction with their visit (4.76 out of 5) and their provider (4.98 out of 5). Patients slightly disagreed with the notion that telehealth is equivalent to in-person provider visits (2.95 out of 5). This did not affect their perception to telehealth itself. It did not discourage patients from recommending telehealth or their provider to future patients. Patients overall felt that attire of the provider does not influence their opinion as to the standard of care they received. Returning patients versus new patient visits were more likely to recommend telehealth to others (4.83 vs. 4.56,
= 0.04). The responses from both groups were overwhelmingly positive.
Telehealth is a viable clinic option in an orthopedic sports medicine clinic. Patients who have seen providers in-person previously are more likely to recommend telehealth versus new patients. New patients were satisfied with their telehealth experience.
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