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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 SilvermanHandmaker 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. [ABSTRACT FROM AUTHOR]

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? Methods: A survey was generated using Academy of Critical Care: Development, Evaluation, and Methodology guidelines. Two focus groups with seven attending orthopaedic surgeons who participate in the Collaborative Orthopaedic Education Research Group and who are experts on gender diversity in orthopaedics were held to improve survey validity. The survey included binary-response, Likert, and free-text questions on the perception of professional, social, and personal interactions held by the resident being surveyed. The questions focused on a respondent's perception of interactions with staff members, patients, resident colleagues, and attending surgeons, as well as sexual harassment. Program directors at 10 selected Accreditation Council for Graduate Medical Education (ACGME)–accredited orthopaedic residency programs that participate in the Collaborative Orthopaedic Education Research Group shared the survey with residents at their institutions. There were 95 programs in the Collaborative Orthopaedic Education Research Group at the time this survey was distributed. In this program, directors or other interested teaching faculty in orthopaedic residency programs voluntarily participate to discuss and develop quality research on resident and fellow education. These 95 programs account for 46% of the ACGME-accredited programs in the United States at the time the survey was created and distributed. The 10 residency programs had a total of 232 enrolled residents; 15% (34) identified as women. This gender distribution models the national sample of orthopaedic residents. Survey reliability was assessed by calculating the Cronbach alpha after determining the variance in each relevant (nondemographic) survey item. The final survey was found to have excellent internal reliability (alpha = 0.95). Responses from residents identifying as women and those identifying as men were compared using Fisher exact tests for all categorical data, and two-tailed independent t-tests were used for all continuous data. Differences in each survey category (professional interactions, social interactions, personal interactions, and sexual harassment in preresidency interview experiences) were calculated. Results: Women reported experiencing microaggressions (left undefined to the survey respondent, but generally considered to be subtle, stunning, often automatic, and nonverbal exchanges that are "put downs") at work more frequently than men did (40% [six of 15] versus 5% [four of 74]; p < 0.001). Specifically, women perceived being interrupted (53% [eight of 15] versus 5% [four of 75]); p < 0.001) by men colleagues, called by their first name (67% [10 of 15] versus 4% [3 of 72]; p < 0.001), and given administrative tasks (27% [four of 15] versus 1% [one of 75]; p = 0.004) more often than men. More women than men perceived that patients (33% [five of 15] versus 0 of 74 [0%]; p < 0.001) and hospital staff (27% [four of 15] versus 7% [five of 74]; p = 0.01) respected their opinion less than that of men. More women than men perceived that group humor negatively targeted their gender (47% [seven of 15] versus 1% [one of 75]; p < 0.001) and that criticism of their surgical skill was based on their gender rather than their ability (33% [five of 15] versus 5% [four of 78]; p = 0.005). In residency or subinternship interviews, 20% of women reported experiencing sexual harassment as defined by a listing of known types of harassment in the question stem, compared with 0% of men (p = 0.004). Women reported harassment in the form of verbal remarks of a sexual nature and obscene images in the workplace, whereas men did not report any form of harassment during interviews. Conclusion: These findings suggest that the greatest discrepancies in the perceived experiences of women and men residents lie in professional interactions, and women residents are more likely to experience sexual harassment and disparaging humor than men residents. Clinical Relevance: Addressing these discrepancies, particularly in the professional setting, will help to create a more inclusive work environment and attract more women to orthopaedic surgery. Annual distribution of the survey used in this study by program directors to residents in their programs can help to identify discrepant perceptions that, coupled with the collection of objective data, can be targeted for improvement. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the gender composition of fellows, faculty, and leaders within orthopaedic sports medicine fellowship programs to provide a more complete analysis of gender diversity within this subspecialty., Methods: Official program websites of orthopaedic sports medicine fellowships listed on the Arthroscopy Association of North America (AANA) fellowship directory were examined. Data collected for analysis included the gender of program directors, fellowship faculty, orthopaedic surgery department faculty, current sports medicine fellows, and fellows who graduated within the last five years., Results: Of the 132 orthopaedic sports medicine fellows in training in the United States in the 2021-2022 academic year, 113 (85.6%) were men and 19 (14.4%) were women (p<0.001). Within the past five years, 419 fellows were listed as completing a sports medicine fellowship, with 375 (89.5%) being men, and 44 (10.5%) being women (p<0.001). There was no significant difference in the gender composition of current fellows compared to the composition of fellows within the last 5 years (p=0.74). When examining gender trends in sports medicine faculty, 639 (86.6%) were men and 99 (13.4%) were women (p<0.001). There were 14 women (14.4%) orthopaedic sports medicine faculty in leadership positions (i.e., program director or assistant program director) compared to 83 men in such positions (85.6%) (p<0.001) CONCLUSIONS: Orthopaedic sports medicine fellowships remain heavily male-dominated on all levels, including fellows, faculty, and leadership. There were no differences in the gender composition of current fellows when compared to those who graduated in the last five years, suggesting persistent gender disparity and the need for novel initiatives to enhance gender diversity in sports medicine., (Copyright © 2023. Published by Elsevier Inc.)