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Understanding the risk factors that contribute to post-mastectomy complications can better inform preoperative discussions. Here, we assess the impact of the 5-Factor Frailty Index Score (mFI-5) in predicting 30-day postoperative complications in patients undergoing mastectomy. A retrospective review of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) data base was conducted for patients older than 65 undergoing mastectomy between 2010 and 2015. We assessed each patient's Frailty Index Score using the mFI-5. Primary outcomes included wound complications and overall complications. Multivariate logistic and linear regression analyses were used to determine the ability of the mFI-5 to predict postoperative outcomes. A total of 13,783 patients were analyzed. The rate of wound complications was 3.0%, while the rate of overall complications was 6.0%. An mFI-5 score greater than 2 was an independent risk factor for wound complications and overall complications. Overall, patients undergoing mastectomy with an mFI-5 of 2 or greater experienced higher rates of postoperative complications. The mFI-5 is an accessible tool that can be used to risk-stratify patients undergoing mastectomy and can positively contribute to the informed consent and shared decision-making process., (© 2021 Wiley Periodicals LLC.)

Unveiling the molecular mechanisms underlying tissue regeneration provides new opportunities to develop treatments for diabetic ulcers and other chronic skin lesions. Here, we show that Ccl2 secretion by epidermal keratinocytes is directly orchestrated by Nrf2, a prominent transcriptional regulator of tissue regeneration that is activated early after cutaneous injury. Through a unique feedback mechanism, we find that Ccl2 from epidermal keratinocytes not only drives chemotaxis of macrophages into the wound but also triggers macrophage expression of EGF, which in turn activates basal epidermal keratinocyte proliferation. Notably, we find dysfunctional activation of Nrf2 in epidermal keratinocytes of diabetic mice after wounding, which partly explains regenerative impairments associated with diabetes. These findings provide mechanistic insight into the critical relationship between keratinocyte and macrophage signaling during tissue repair, providing the basis for continued investigation of the therapeutic value of Nrf2., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Study Design: Mixed-methods with cross-sectional survey and interviews., Introduction: Hand therapy is a specialty area of practice for occupational (OT) and physical therapists (PT), requiring experience and certification beyond entry-level generalist education. Perspectives and inclusion of content related to hand therapy differs among entry-level OT programs and faculty., Purpose: Perception and inclusion of hand therapy content in OT programs was examined in this mixed-method study to better understand the trends in academia regarding integration of content related to hand therapy., Methods: A survey was developed, peer-reviewed, and emailed to all accredited entry-level masters and doctorate OT programs via Survey Monkey (SurveyMonkey, Inc., San Mateo, CA). Respondents were also given the opportunity to participate in an interview (n = 2; 5%)., Results: A total of 43 participants responded to the survey, representing a 23% response rate. Quantitative results revealed that 65% of OT programs report including 41+ hours of hand therapy content and 54% report integration of hand therapy content in 2-3 courses. Qualitative trends included the perception of hand content as necessary and beneficial to other areas of practice as well as the perspective that it is too specialized and advanced for generalist curriculum., Discussion: Educators have a largely positive opinion regarding inclusion and generalizability of hand therapy content within OT curricula with varied content inclusion. While hand therapy related content is valued, increased emphasis on occupation during didactic instruction is recommended for more holistic understanding and occupation-based practice., Conclusion: While trends of hand therapy content inclusion were revealed in the survey, perceptions of hand therapy within the broad spectrum of OT curricula were diverse, indicating a possible lack of unity within the profession regarding this specialty area of practice., (Copyright © 2018 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.)

Cytoglobin is a widely expressed heme protein that binds oxygen, carbon monoxide and nitric oxide. Recent examination of cytoglobin in the vasculature indicates that it contributes to nitric oxide availability, which is central to normal blood vessel function through regulation of smooth muscle cell tone and physiological response. Given the potential implications of cytoglobin in vascular function, we examined how cytoglobin might be uniquely regulated in vascular smooth muscle cells. Our data demonstrate that endothelial cells can increase the expression of cytoglobin in vascular smooth muscle cells, and the induction of cytoglobin is cell contact-dependent. We show that Notch signaling is necessary for endothelial cell-induced cytoglobin expression and Notch2 and Notch3 are sufficient to drive its expression in aortic smooth muscle cells. We further reveal that in cytoglobin-depleted smooth muscle cells there is increased cellular nitric oxide. These data demonstrate that, in addition to being the main producer of vascular nitric oxide, endothelial cells facilitate the ability of smooth muscle cells to metabolize nitric oxide through upregulation of cytoglobin. Our results reveal a novel mechanism by which Notch signaling contributes to vascular function through regulation of a gene that controls nitric oxide levels., (Copyright © 2018 Elsevier Inc. All rights reserved.)