Our results suggest that the deletion of AT2 receptor reduced SHP-1 activity and restored VEGF actions, leading to an increased blood flow reperfusion after ischemia in diabetes mellitus.

Negative-pressure wound therapy (NPWT) has significantly improved healing rates and patient comfort since its inception. However, a considerable number of questions have been raised regarding its mechanisms of action. Many health care workers and researchers have attempted to clarify the role of NPWT in wound healing. The purpose of this perspective article is to assemble some of the concepts that have been put forward in order to propose an integrated view of the mechanisms involved in NPWT. Particular emphasis will be placed on mechanically induced tissue deformations and their involvement in some of the key processes of wound healing, including nutrient and oxygen transport, blood vessel formation, and cellular proliferation and differentiation, mainly of myofibroblasts.

Background: Since the 1990s, new techniques for the treatment of varicose veins have emerged, including radiofrequency ablation (RFA) and laser treatment. We performed a study to compare the safety, efficacy and outcomes of RFA compared to those of open surgery and laser ablation for the treatment of varicose veins. We also carried out a cost analysis of RFA compared to open surgery to assess whether RFA could help free up operating room time by being performed in an outpatient context. Methods:We conducted a systematic literature review (publication date May 2010-September 2013 for articles in English, January 1991-September 2013 for those in French). We used several checklists to measure the quality of the studies. We also collected data on costing. Results:The literature search identified 924 publications, of which 38 were retained for analysis: 15 literature reviews, 1 good-practice guideline and 22 new primary studies. The overall level of evidence was low to moderate owing to the limited sample sizes, lack of information on patient characteristics and lack of standardization of the outcome measures. However, the results obtained are consistent from study to study. In the short and medium term, RFA is considered as effective as open surgery or laser treatment (moderate level of evidence) and presents fewer major and minor complications than open surgery (low level of evidence). Radiofrequency ablation can be performed on an outpatient basis. We calculated that RFA would be about $110-$220 more expensive per patient than open surgery. Conclusion:Radiofrequency ablation is a valuable alternative to open surgery and would free up operating room time in a context of low accessibility.

Objective: Critical limb ischemia is a major complication of diabetes characterized by insufficient collateral vessel development and proper growth factor signaling unresponsiveness. Although mainly deactivated by hypoxia, phosphatases are important players in the deregulation of proangiogenetic pathways. Previously, SHP-1 (Scr homology 2-containing phosphatase-1) was found to be associated with the downregulation of growth factor actions in the diabetic muscle. Thus, we aimed to gain further understanding of the impact of SHP-1 on smooth muscle cell (SMC) function under hypoxic and diabetic conditions. Approach and Results: Despite being inactivated under hypoxic conditions, high glucose level exposure sustained SHP-1 phosphatase activity in SMC and increased its interaction with PDGFR (platelet-derived growth factor receptor)-β, thus reducing PDGF proangiogenic actions. Overexpression of an inactive form of SHP-1 fully restored PDGF-induced proliferation, migration, and signaling pathways in SMC exposed to high glucose and hypoxia. Nondiabetic and diabetic mice with deletion of SHP-1 specifically in SMC were generated. Ligation of the femoral artery was performed, and blood flow was measured for 4 weeks. Blood flow reperfusion, vascular density and maturation, and limb survival were all improved while vascular apoptosis was attenuated in diabetic SMC-specific SHP-1 null mice as compared to diabetic mice. Conclusions: Diabetes and high glucose level exposure maintained SHP-1 activity preventing hypoxia-induced PDGF actions in SMC. Specific deletion of SHP-1 in SMC partially restored blood flow reperfusion in the diabetic ischemic limb. Therefore, local modulation of SHP-1 activity in SMC could represent a potential therapeutic avenue to improve the proangiogenic properties of SMC under ischemia and diabetes.

Cardiovascular disease is the leading cause of death worldwide. This disease includes chronic total occlusion (CTO), which is a complete blockage of an artery. Unlike partial occlusions, CTOs are difficult to cross percutaneously using conventional guidewires (thin and flexible wires) because of the fibrotic and calcified nature of the blockage. The lack of data regarding the mechanical properties of CTO limits the development of new technologies in the field of percutaneous coronary intervention (PCI) and percutaneous peripheral intervention (PPI). In this study, calcified plaques retrieved from occluded arteries are analyzed in order to better understand their mechanical properties and to help propose an artificial analogue. Calcified plaques samples were collected from the superficial femoral artery wall within one hour following a lower limb amputation surgery. These samples were studied to determine their composition and mechanical properties. The same characterization procedures were performed on various potential artificial analogues. These analogues include three plaster materials and dense hydroxyapatite blocks. The results were then compared with those of the calcified plaques in order to determine the more favorable analogue. This mechanical analysis and the proposal of a potential analogue for the calcified plaques found in occluded arteries could benefit the development of new technologies and devices in the field PCI and PPI.

Aims: Peripheral artery disease is a complication of diabetes leading to critical hindlimb ischemia. Diabetes-induced inhibition of VEGF actions is associated with the activation of protein kinase Cδ (PKCδ). We aim to specifically investigate the role of PKCδ in endothelial cell (EC) function and VEGF signaling. Methods: Nondiabetic and diabetic mice, with ( ec-Prkcd−/−) or without ( ec-Prkcdf/f) endothelial deletion of PKCδ, underwent femoral artery ligation. Blood flow reperfusion was assessed up to 4 weeks post-surgery. Capillary density, EC apoptosis and VEGF signaling were evaluated in the ischemic muscle. Src homology region 2 domain-containing phosphatase-1 (SHP-1) phosphatase activity was assessed in vitro using primary ECs. Results: Ischemic muscle of diabetic ec-Prkcdf/f mice exhibited reduced blood flow reperfusion and capillary density while apoptosis increased as compared to nondiabetic ec-Prkcdf/f mice. In contrast, blood flow reperfusion and capillary density were significantly improved in diabetic ec-Prkcd−/− mice. VEGF signaling pathway was restored in diabetic ec-Prkcd−/− mice. The deletion of PKCδ in ECs prevented diabetes-induced VEGF unresponsiveness through a reduction of SHP-1 phosphatase activity. Conclusions: Our data provide new highlights in mechanisms by which PKCδ activation in EC contributed to poor collateral vessel formation, thus, offering novel therapeutic targets to improve angiogenesis in the diabetic limb.

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Background Alpine skiing rescues are challenging because of the mountainous environment and risks of cervical spine motion (CSM) induced during victims’ extrications (EXs) and downhill evacuations (DEs). The benefits of applying a cervical collar (CC) over manual in-line stabilization without CC (MILS) in terms of spinal motion restriction during simulated alpine rescues are undocumented. Our hypothesis was that CSM recorded using MILS alone is non-inferior to CSM recorded with a CC according to a 10 degrees margin. Methods A total of 32 alpine extrications and 4 downhill evacuations on different slope conditions were performed using a high fidelity mannequin designed with a motion sensors instrumented cervical spine. The primary outcome was the peak extrication 3D excursion angle (Peak 3D θEX,) of the mannequin’s head. The secondary objectives were to describe the time to extrication completion (tEX) and to highlight which extrication manipulation is more likely to induce CSM. Results The median Peak 3D θEX recorded during flat terrain extrications using CC was 10.77° (95% CI 7.31°–16.45°) compared to 13.06° (95% CI 10.20°–30.36°) using MILS, and 16.09° (95% CI 9.07°–37.43°) for CC versus 16.65° (95% CI 13.80°–23.40°) using MILS on a steep slope. Peak 3D θEX with CC or using MILS during extrications were equivalent according to a 10 degrees non-inferiority hypothesis testing (p < 0.05). Time to extrication completion (tEX) was significantly reduced using MILS without CC on a flat terrain with a median duration of 237,3 s (95% CI 197.8 s, 272.2 s) compared to 358.7 s (95% CI 324.1 s, 472.4 s). During downhill evacuations, CSM with and without CC across all terrain conditions were negligible (< 5°). When CC is used; its installation manipulation induces the highest CSM. When EXs are done using MILS without CC, the logroll initiation is the manipulation inducing the highest risk of CSM. Conclusion For experienced ski patrollers, the biomechanical benefits of spinal motion restriction provided by CC over MILS during alpine skiing rescues appear to be marginal and CC use negatively affects rescue time.