ABSTRACT
In diabetes, stromal cell-derived factor-1 (SDF-1) expression and progenitor cell recruitment are reduced. Dipeptidyl peptidase-4 (DPP-4) inhibits SDF-1 expression and progenitor cell recruitment. Here we examined the impact of the DPP-4 inhibitor, MK0626, on progenitor cell kinetics in the context of wound healing. Wildtype (WT) murine fibroblasts cultured under high-glucose to reproduce a diabetic microenvironment were exposed to MK0626, glipizide, or no treatment, and SDF-1 expression was measured with ELISA. Diabetic mice received MK0626, glipizide, or no treatment for 6 weeks and then were wounded. Immunohistochemistry was used to quantify neovascularization and SDF-1 expression. Gene expression was measured at the RNA and protein level using quantitative polymerase chain reaction and ELISA, respectively. Flow cytometry was used to characterize bone marrow-derived mesenchymal progenitor cell (BM-MPC) population recruitment to wounds. BM-MPC gene expression was assayed using microfluidic single cell analysis. WT murine fibroblasts exposed to MK0626 demonstrated increased SDF-1 expression. MK0626 treatment significantly accelerated wound healing and increased wound vascularity, SDF-1 expression, and dermal thickness in diabetic wounds. MK0626 treatment increased the number of BM-MPCs present in bone marrow and in diabetic wounds. MK0626 had no effect on BM-MPC population dynamics. BM-MPCs harvested from MK0626-treated mice exhibited increased chemotaxis in response to SDF-1 when compared to diabetic controls. Treatment with a DPP-4 inhibitor significantly improved wound healing, angiogenesis, and endogenous progenitor cell recruitment in the setting of diabetes.
Subject(s)
Diabetes Mellitus, Experimental/complications , Dipeptidyl Peptidase 4/drug effects , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Hematopoietic Stem Cells/drug effects , Neovascularization, Pathologic , Wound Healing/drug effects , Wounds and Injuries/physiopathology , Animals , Chemokine CXCL12/metabolism , Glipizide/pharmacology , Hematopoietic Stem Cells/cytology , Mice , Mice, Inbred C57BL , Triazoles/pharmacologyABSTRACT
Women are less likely to reach top-level leadership positions, and more likely to leave academic positions, than men, and are likely to earn less money than men. Women are also less likely to initiate a negotiation-a process that is crucial for professional advancement. This reluctance to ask hinders their advancement and can have long-lasting consequences-both financial and professional. The reasons that women do not ask are multifactorial. In this article, we will explore reasons why women are less likely to negotiate, the barriers they face when they do, and strategies that women can apply to improve their negotiation skills.
Subject(s)
Negotiating , Women/psychology , Female , Humans , Income/statistics & numerical data , Interpersonal RelationsABSTRACT
BACKGROUND: Diabetes and aging are known risk factors for impaired neovascularization in response to ischemic insult, resulting in chronic wounds, and poor outcomes following myocardial infarction and cerebrovascular injury. Hypoxia-inducible factor (HIF)-1α, has been identified as a critical regulator of the response to ischemic injury and is dysfunctional in diabetic and elderly patients. To better understand the role of this master hypoxia regulator within cutaneous tissue, the authors generated and evaluated a fibroblast-specific HIF-1α knockout mouse model. METHODS: The authors generated floxed HIF-1 mice (HIF-1) by introducing loxP sites around exon 1 of the HIF-1 allele in C57BL/6J mice. Fibroblast-restricted HIF-1α knockout (FbKO) mice were generated by breeding our HIF-1 with tamoxifen-inducible Col1a2-Cre mice (Col1a2-CreER). HIF-1α knockout was evaluated on a DNA, RNA, and protein level. Knockout and wild-type mice were subjected to ischemic flap and wound healing models, and CD31 immunohistochemistry was performed to assess vascularity of healed wounds. RESULTS: Quantitative real-time polymerase chain reaction of FbKO skin demonstrated significantly reduced Hif1 and Vegfa expression compared with wild-type. This finding was confirmed at the protein level (p < 0.05). HIF-1α knockout mice showed significantly impaired revascularization of ischemic tissue and wound closure and vascularity (p < 0.05). CONCLUSIONS: Loss of HIF-1α from fibroblasts results in delayed wound healing, reduced wound vascularity, and significant impairment in the ischemic neovascular response. These findings provide new insight into the importance of cell-specific responses to hypoxia during cutaneous neovascularization.
Subject(s)
Gene Deletion , Gene Expression Regulation , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Neovascularization, Pathologic/genetics , Wound Healing/genetics , Animals , Cells, Cultured , Disease Models, Animal , Fibroblasts/cytology , Fibroblasts/physiology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Random Allocation , Real-Time Polymerase Chain Reaction , Sensitivity and Specificity , Wound Healing/physiologyABSTRACT
Orthopaedic and hand surgeons frequently treat disorders of the flexor and extensor tendon systems. Common conditions, such as trigger finger, de Quervain tenosynovitis, extensor tendon injury, and zone II flexor tendon injury, can be challenging to treat. Complications that limit normal hand function still occur despite advances in surgical techniques and therapy protocols. It is helpful to be aware of the complications related to the treatment of these hand disorders and understand surgical techniques to minimize their frequency.
Subject(s)
Hand Injuries/surgery , Medical Errors/adverse effects , Postoperative Complications , Tendinopathy/surgery , Wrist Injuries/surgery , Hand Injuries/diagnosis , Hand Injuries/etiology , Humans , Tendinopathy/diagnosis , Tendinopathy/etiology , Wrist Injuries/diagnosis , Wrist Injuries/etiologyABSTRACT
BACKGROUND: This study was designed to establish the essential hand surgery procedures that should be mastered by graduating plastic surgery residents. This framework can then be used as a guideline for developing Objective Structured Assessment of Technical Skill to teach technical skills in hand surgery. METHODS: Ten expert hand surgeons were surveyed regarding the essential hand surgery procedures that should be mastered by graduating plastic surgery residents. The top 10 procedures from this survey were then used to survey all 89 Accreditation Council for Graduate Medical Education-approved plastic surgery program directors. RESULTS: There was a 69 percent response rate to the program director survey (n = 61). The top nine hand surgery procedures included open carpal tunnel release, open A1 pulley release, digital nerve repair with microscope, closed reduction and percutaneous pinning of metacarpal fracture, excision of dorsal or volar ganglion, zone II flexor tendon repair with multistrand technique, incision and drainage of the flexor tendon sheath for flexor tenosynovitis, flexor tendon sheath steroid injection, and open cubital tunnel release. CONCLUSIONS: Surgical educators need to develop objective methods to teach and document technical skill. The Objective Structured Assessment of Technical Skill is a valid method for accomplishing this task. There has been no consensus regarding which hand surgery procedures should be mastered by graduating plastic surgery residents. The authors have identified nine procedures that are overwhelmingly supported by plastic surgery program directors. These nine procedures can be used as a guideline for developing Objective Structured Assessment of Technical Skill to teach and document technical skills in hand surgery.
Subject(s)
Carpal Tunnel Syndrome/surgery , Clinical Competence , Education, Medical, Graduate/standards , Fellowships and Scholarships/standards , Plastic Surgery Procedures/education , Surgery, Plastic/education , Accreditation , Data Collection , Faculty, Medical , Hand/surgery , Humans , Internship and Residency/standardsABSTRACT
PURPOSE: To establish the essential hand surgery procedures that should be mastered by graduating orthopedic surgery residents. This framework can then be used as a guideline for developing an Objective Structured Assessment of Technical Skill to teach and document technical skill in hand surgery. METHODS: A select group of 10 expert hand surgeons was surveyed regarding the essential hand surgery procedures that should be mastered by graduating orthopedic surgery residents. The top 10 procedures from this survey were then used to survey all 155 American Council of Graduate Medical Education-approved orthopedic surgery program directors regarding the essential procedures that should be mastered by graduating orthopedic surgery residents. RESULTS: We had a 39% response rate to the program director survey. The top 8 hand surgery procedures as determined by the orthopedic surgery program directors included open carpal tunnel release, open A1 pulley release, open reduction internal fixation of distal radius fracture, flexor tendon sheath steroid injection, excision of dorsal or volar ganglion, closed reduction and percutaneous pinning of metacarpal fracture, open cubital tunnel release, and incision and drainage of flexor tendon sheath for flexor tenosynovitis. CONCLUSIONS: Surgical educators need to develop objective methods to teach and document technical skill. The Objective Structured Assessment of Technical Skill is a valid method to accomplish this task. However, there has been no consensus regarding which hand surgery procedures should be mastered by graduating orthopedic surgery residents. We have identified 8 procedures that were overwhelmingly supported by orthopedic surgery program directors. These 8 procedures can be used as a guideline for developing an Objective Structured Assessment of Technical Skill to teach and document technical skill in hand surgery. CLINICAL RELEVANCE: This study addresses the future of orthopedic surgery education as it pertains to hand surgery.
