Axonal growth arrests after an increased accumulation of Schwann cells expressing senescence markers and stromal cells in acellular nerve allografts

Acellular nerve allografts (ANAs) and other nerve constructs do not reliably facilitate axonal regeneration across long defects (>3 cm). Causes for this deficiency are poorly understood. In this study, we determined what cells are present within ANAs before axonal growth arrest in nerve constructs and if these cells express markers of cellular stress and senescence. Using the Thy1-GFP rat and serial imaging, we identified the time and location of axonal growth arrest in long (6 cm) ANAs. Axonal growth halted within long ANAs by 4 weeks, while axons successfully regenerated across short (3 cm) ANAs. Cellular populations and markers of senescence were determined using immunohistochemistry, histology, and senescence-associated β-galactosidase staining. Both short and long ANAs were robustly repopulated with Schwann cells (SCs) and stromal cells by 2 weeks. Schwann cells (S100β(+)) represented the majority of cells repopulating both ANAs. Overall, both ANAs demonstrated similar cellular populations with the exception of increased stromal cells (fibronectin(+)/S100β(−)/CD68(−) cells) in long ANAs. Characterization of ANAs for markers of cellular senescence revealed that long ANAs accumulated much greater levels of senescence markers and a greater percentage of Schwann cells expressing the senescence marker p16 compared to short ANAs. To establish the impact of the long ANA environment on axonal regeneration, short ANAs (2 cm) that would normally support axonal regeneration were generated from long ANAs near the time of axonal growth arrest (“stressed” ANAs). These stressed ANAs contained mainly S100β(+)/p16(+) cells and markedly reduced axonal regeneration. In additional experiments, removal of the distal portion (4 cm) of long ANAs near the time of axonal growth arrest and replacement with long isografts (4 cm) rescued axonal regeneration across the defect. Neuronal culture derived from nerve following axonal growth arrest in long ANAs revealed no deficits in axonal extension. Overall, this evidence demonstrates that long ANAs are repopulated with increased p16(+) Schwann cells and stromal cells compared to short ANAs, suggesting a role for these cells in poor axonal regeneration across nerve constructs

Five Financial Pearls for Medical Students, Residents, and Young Surgeons

Background:. Finances impact every aspect of our daily lives. Despite this, they are rarely discussed in medical school or surgical training. Consequently, more than half the medical students we interview report no formal teaching about personal finance. The purpose of this article was to present 5 topics every graduating medical student, resident, and young surgeon should understand to start the path to financial independence. Methods:. We synthesized recommendations and data from several books on financial literacy, blogs on the topic, and the personal experiences of the 4 authors. Results:. The following 5 topics were identified as critical for young surgeons: learn about and manage your own finances, consider the financial implications of your career choices, make a plan to pay off your student loans, make a budget and stick to it, and think carefully before buying property. Central to these 5 lessons is the idea that starting to invest and save early is essential to taking advantage of interest and capital gains. We also demonstrate pay and cost differences in 5 regions of the country and outline the 2 main pathways one can take to repaying their student loans. Conclusions:. Financial literacy is an important aspect of being an effective surgeon. With minimal effort, you can take these 5 steps now toward financial freedom. Doing so will improve your sense of control over your financial life and decrease anxiety about the unknown