Background Women residents are underrepresented in orthopaedic surgery. The causes of the deficit of women in orthopaedic surgery are multifactorial, but by identifying the perceptions of women in orthopaedic residency training and comparing them with the perceptions of men, we can improve our understanding of ways to enhance the recruitment of qualified and diverse candidates.Questions/purposes (1) What differences exist in the perceived experiences of residents identifying as women and men regarding professional, social, and personal interactions during residency training? (2) Are there differences in the percentage of women and men residents who have experienced harassment or discrimination in preresidency interviews, and are there differences in the type of harassment or discrimination experienced? a Members of the Collaborative Orthopaedic Educational Research Group are listed in an Appendix at the end of this article. One of the authors (SEA) serves as Chair, Accreditation Council for Graduate Medical Education Residency Review Committee, Orthopaedic Surgery 2021 to 2024. One of the authors (KJT) has received honorarium for lectures, during the study period, in an amount of less than USD 10,000 and serves as an American Medical Association delegate from the American Academy of Orthopaedic Surgeons as well as a member of the

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Perlecan is a 500 kDa proteoglycan residing in the extracellular matrix of endothelial basement membranes with five distinct protein domains and three heparan sulfate chains. The complex structure of perlecan and the interaction it has with its local environment accounts for its various cellular and tissue-related effects, to include cartilage, bone, neural and cardiac development, angiogenesis, and blood brain barrier stability. As perlecan is a key contributor to extracellular matrix health involved in many tissues and processes throughout the body, dysregulation of perlecan has the potential to contribute to various neurological and musculoskeletal diseases. Here we review key findings associated with perlecan dysregulation in the context of disease. This is a narrative review article examining perlecan’s role in diseases of neural and musucloskeletal pathology and its potential as a therapeutic index. Literature searches were conducted on the PubMed database, and were focused on perlecan’s impact in neurological disease, to include ischemic stroke, Alzheimer’s Disease (AD) and brain arteriovenous malformation (BAVM), as well as musculoskeletal pathology, including Dyssegmental Dysplasia Silverman-Handmaker type (DDSH), Schwartz-Jampel syndrome (SJS), sarcopenia, and osteoarthritis (OA). PRISMA guidelines were utilized in the search and final selection of articles.Increased perlecan levels were associated with sarcopenia, OA, and BAVM, while decreased perlecan was associated with DDSH, and SJS. We also examined the therapeutic potential of perlecan signaling in ischemic stroke, AD, and osteoarthritic animal models. Perlecan experimentally improved outcomes in such models of ischemic stroke and AD, and we found that it may be a promising component of future therapeutics for such pathology. In treating the pathophysiology of sarcopenia, OA, and BAVM, inhibiting the effect of perlecan may be beneficial. As perlecan binds to both α-5 integrin and VEGFR2 receptors, tissue specific inhibitors of these proteins warrant further study. In addition, analysis of experimental data revealed promising insight into the potential uses of perlecan domain V as a broad treatment for ischemic stroke and AD. As these diseases have limited therapeutic options, further study into perlecan or its derivatives and its potential to be used as novel therapeutic for these and other diseases should be seriously considered.

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