RESUMEN
Rationale: Elevated shear stress (ESS) induces vascular remodeling in veins exposed to arterial blood flow, which can lead to arteriovenous (AV) fistula failure. The molecular mechanisms driving remodeling have not been comprehensively examined with a single-cell resolution before. Objective: Using an in vivo animal mode, single-cell RNA sequencing, and histopathology, we precisely manipulate blood flow to comprehensively characterize all cell subpopulations important during vascular remodeling. Methods: AV loops were created in saphenous vessels of rats using a contralateral saphenous vein interposition graft to promote ESS. Saphenous veins with no elevated shear stress (NSS) were anastomosed as controls. Findings: ESS promoted transcriptional homogeneity, and NSS promoted considerable heterogeneity. Specifically, ESS endothelial cells (ECs) showed a more homogeneous transcriptional response promoting angiogenesis and upregulating endothelial-to-mesenchymal transition inhibiting genes (Klf2). NSS ECs upregulated antiproliferation genes such as Cav1, Cst3, and Btg1. In macrophages, ESS promoted a large homogeneous subpopulation, creating a mechanically activated, proinflammatory and thus proangiogenic myeloid phenotype, whereas NSS myeloid cells expressed the anti-inflammatory and antiangiogenetic marker Mrc1. Conclusion: ESS activates unified gene expression profiles to induce adaption of the vessel wall to hemodynamic alterations. Targeted depletion of the identified cellular subpopulations may lead to novel therapies to prevent excessive venous remodeling, intimal hyperplasia, and AV fistula failure.
RESUMEN
Objective: Given the significant economic, health care, and personal burden of acute and chronic wounds, we investigated the dose dependent wound healing mechanisms of two Avena sativa derived compounds: avenanthramide (AVN) and ß-Glucan. Approach: We utilized a splinted excisional wound model that mimics human-like wound healing and performed subcutaneous AVN and ß-Glucan injections in 15-week-old C57BL/6 mice. Histologic and immunohistochemical analysis was performed on the explanted scar tissue to assess changes in collagen architecture and cellular responses. Results: AVN and ß-Glucan treatment provided therapeutic benefits at a 1% dose by weight in a phosphate-buffered saline vehicle, including accelerated healing time, beneficial cellular recruitment, and improved tissue architecture of healed scars. One percent AVN treatment promoted an extracellular matrix (ECM) architecture similar to unwounded skin, with shorter, more randomly aligned collagen fibers and reduced inflammatory cell presence in the healed tissue. One percent ß-Glucan treatment promoted a tissue architecture characterized by long, thick bundles of collagen with increased blood vessel density. Innovation: AVN and ß-Glucan have previously shown promise in promoting wound healing, although the therapeutic efficacies and mechanisms of these bioactive compounds remain incompletely understood. Furthermore, the healed ECM architecture of these wounds has not been characterized. Conclusions: AVN and ß-Glucan accelerated wound closure compared to controls through distinct mechanisms. AVN-treated scars displayed a more regenerative tissue architecture with reduced inflammatory cell recruitment, while ß-Glucan demonstrated increased angiogenesis with more highly aligned tissue architecture more indicative of fibrosis. A deeper understanding of the mechanisms driving healing in these two naturally derived therapeutics will be important for translation to human use.
Asunto(s)
Cicatriz , beta-Glucanos , ortoaminobenzoatos , Animales , Ratones , beta-Glucanos/farmacología , Colágeno , Ratones Endogámicos C57BL , Cicatrización de HeridasAsunto(s)
Internado y Residencia , Radiología , Estudiantes de Medicina , Humanos , Radiografía , Radiología/educación , Estados UnidosRESUMEN
BACKGROUND/OBJECTIVE: Online physician-rating websites are being increasingly used by patients to gauge physicians' quality of service. The objective of this study is to assess the impact of residency training background of hair restoration surgeons and to identify themes of patient reviews using online physician-rating portals. METHOD: From July 1, 2018 to July 18, 2018, a list of American Board of Hair Restoration Surgery (ABHRS) physicians was compiled. Each member's name was searched on Healthgrades.com and Yelp.com websites, and profile reviews were analyzed for themes of patient satisfaction and dissatisfaction. RESULTS: Eighty-six ABHRS-certified surgeons were identified on the ABHRS physician directory practicing in the United States. Eleven different residency training backgrounds are represented. Surgeons were given significantly higher ratings on Healthgrades (4.63 vs 3.77, P < 0.001), and nonsurgeons were given significantly higher ratings on Yelp (4.31 vs 4.11, P = 0.036). A total of 567 five-star reviews and 59 one-star reviews were analyzed for content across both physician review portals. The most commonly cited topics included results, office staff, physician's bedside manner, comfort during procedure, patient-perceived physician's honesty, patient-perceived physician's knowledge, cost/financing options, recovery time, and wait time/scheduling. CONCLUSIONS: Significant, yet inconsistent differences in ratings were found between surgical and nonsurgical residency backgrounds across online physician-rating portals. Understanding drivers of positive and negative reviews may help surgeons improve patient satisfaction.