Assuntos
Tomada de Decisão Clínica/métodos , Disfunção Cognitiva , Assistência Perioperatória/métodos , Procedimentos Cirúrgicos Vasculares , Idoso de 80 Anos ou mais , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/terapia , Humanos , Masculino , Cuidados Paliativos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controleAssuntos
Atenção Primária à Saúde/métodos , Varizes/diagnóstico , Varizes/terapia , Feminino , Humanos , Masculino , Gravidez , Varizes/fisiopatologiaRESUMO
BACKGROUND: Complex abdominal aortic aneurysm (AAA) is a relatively common presentation to the vascular specialist. Despite this there is little consensus on how to manage the often comorbid group of patients. Recent advances in endovascular technology have led to the availability of multiple devices, many of which could be used to treat the same aneurysm. The aim of this study was to quantify this potential variability across vascular specialists from multiple countries. METHODS: An online survey was emailed to members of the Vascular Society for Great Britain and Ireland (VSGBI), the Canadian Society for Vascular Surgery (CSVS) and the Australian and New Zealand Society for Vascular Surgery (ANZSVS). The survey presented a vignette of a 63-year-old woman with significant respiratory comorbidity and a 54 mm juxtarenal AAA (7 mm neck). There were no other adverse morphological features for endovascular repair. The survey included images and questions related to management of the aneurysm. RESULTS: The survey received 238 responses; 61 from ANZSVS, 65 from CSVS and 112 from VSGBI. VSGBI specialists were significantly more likely to continue surveillance than both ANZSVS (odds ratio [OR] 3.41, 95% confidence interval [CI] 1.61-7.65; P<0.001) and CSVS counterparts (OR 2.61, 95% CI: 1.29-5.47; P<0.01). ANZSVS specialists were significantly more likely to perform an endovascular repair than those from CSVS (OR 3.28, 95% CI: 1.50-7.40; P<0.01) and VSGBI (OR 3.65, 95% CI: 1.81-7.59; P<0.001). CSVS specialists were significantly more likely to manage the aneurysm with open surgery than colleagues from the VSGBI (OR 6.57, 95% CI: 2.58-18.46; P<0.001) and ANZSVS (OR 7.18, 95% CI: 2.22-30.79; P<0.001). CONCLUSIONS: Significant variation in the management of a juxtarenal AAA between countries was observed. The same patient would be more likely to have an endovascular repair in Australia and New Zealand, open surgery in Canada and continuing surveillance in the UK and Ireland. This variation reflects the lack of long-term evidence and international consensus on the optimal management of complex AAA.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/tendências , Procedimentos Endovasculares/tendências , Disparidades em Assistência à Saúde/tendências , Padrões de Prática Médica/tendências , Cirurgiões/tendências , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aortografia/tendências , Tomada de Decisão Clínica , Angiografia por Tomografia Computadorizada/tendências , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: M-learning is education using personal mobile electronic devices. Given the prevalence of these in society and amongst healthcare professionals, we aimed to assess their use and feasibility in improving the educational programme of a single vascular institution. METHODS: A weekly vascular departmental teaching programme was initiated with registrars giving 30-min presentations on a defined book chapter. Two multiple-choice questions (MCQ) per session were devised by a supervising consultant utilising the smartphone response system application, Polltogo. A separate investigator disseminated one pre-teaching and one post-teaching MCQ to the attending trainees via a WhatsApp group. Instant feedback of the correct answer was provided by the application. Participants' satisfaction was judged through a survey after 13 sessions. RESULTS: 11 junior doctors of varying seniority participated in the trial. The median number of session attendees was 5. 129 MCQ responses were received. The mobile engagement score (number of answers received divided by total possible answers) was 97.7%. The average correct score for pre-teaching MCQs was 39.4% and post-teaching MCQs 73.0% (p < 0.001). Satisfaction with the concept was high; 80% of responders agreed that it was a useful adjunct to the teaching programme whilst 90% found the system highly user-friendly. CONCLUSIONS: Smartphones can be utilised effectively and with high user satisfaction in assessing knowledge transfer throughout a departmental education programme. Trainees' responses to MCQs significantly improved after 30-min teaching sessions. This concept of m-learning could be developed further to assist with postgraduate examination revision or Deanery teaching programmes in larger cohorts.
Assuntos
Instrução por Computador/métodos , Avaliação Educacional/métodos , Corpo Clínico Hospitalar/educação , Smartphone , Procedimentos Cirúrgicos Vasculares/educação , Estudos de Viabilidade , Retroalimentação , Humanos , Aprendizagem , Satisfação Pessoal , Projetos Piloto , EnsinoRESUMO
Vascular endothelial growth factor A (VEGF-A) binding to the receptor tyrosine kinase VEGFR2 triggers multiple signal transduction pathways, which regulate endothelial cell responses that control vascular development. Multiple isoforms of VEGF-A can elicit differential signal transduction and endothelial responses. However, it is unclear how such cellular responses are controlled by isoform-specific VEGF-A-VEGFR2 complexes. Increasingly, there is the realization that the membrane trafficking of receptor-ligand complexes influences signal transduction and protein turnover. By building on these concepts, our study shows for the first time that three different VEGF-A isoforms (VEGF-A165, VEGF-A121 and VEGF-A145) promote distinct patterns of VEGFR2 endocytosis for delivery into early endosomes. This differential VEGFR2 endocytosis and trafficking is linked to VEGF-A isoform-specific signal transduction events. Disruption of clathrin-dependent endocytosis blocked VEGF-A isoform-specific VEGFR2 activation, signal transduction and caused substantial depletion in membrane-bound VEGFR1 and VEGFR2 levels. Furthermore, such VEGF-A isoforms promoted differential patterns of VEGFR2 ubiquitylation, proteolysis and terminal degradation. Our study now provides novel insights into how different VEGF-A isoforms can bind the same receptor tyrosine kinase and elicit diverse cellular outcomes.
RESUMO
Scavenger receptors (SRs) are a 'superfamily' of membrane-bound receptors that were initially thought to bind and internalize modified low-density lipoprotein (LDL), though it is currently known to bind to a variety of ligands including endogenous proteins and pathogens. New family of SRs and their properties have been identified in recent years, and have now been classified into 10 eukaryote families, defined as Classes A-J. These receptors are classified according to their sequences, although in each class they are further classified based in the variations of the sequence. Their ability to bind a range of ligands is reflected on the biological functions such as clearance of modified lipoproteins and pathogens. SR members regulate pathophysiological states including atherosclerosis, pathogen infections, immune surveillance, and cancer. Here, we review our current understanding of SR structure and function implicated in health and disease.
RESUMO
Vascular endothelial growth factor A (VEGF-A) regulates many aspects of vascular physiology. VEGF-A stimulates signal transduction pathways that modulate endothelial outputs such as cell migration, proliferation, tubulogenesis, and cell-cell interactions. Multiple VEGF-A isoforms exist, but the biological significance of this is unclear. Here we analyzed VEGF-A isoform-specific stimulation of VCAM-1 gene expression, which controls endothelial-leukocyte interactions, and show that this is dependent on both ERK1/2 and activating transcription factor-2 (ATF-2). VEGF-A isoforms showed differential ERK1/2 and p38 MAPK phosphorylation kinetics. A key feature of VEGF-A isoform-specific ERK1/2 activation and nuclear translocation was increased phosphorylation of ATF-2 on threonine residue 71 (T71). Using reverse genetics, we showed ATF-2 to be functionally required for VEGF-A-stimulated endothelial VCAM-1 gene expression. ATF-2 knockdown blocked VEGF-A-stimulated VCAM-1 expression and endothelial-leukocyte interactions. ATF-2 was also required for other endothelial cell outputs, such as cell migration and tubulogenesis. In contrast, VCAM-1 was essential only for promoting endothelial-leukocyte interactions. This work presents a new paradigm for understanding how soluble growth factor isoforms program complex cellular outputs and responses by modulating signal transduction pathways.
Assuntos
Fator 2 Ativador da Transcrição/metabolismo , Leucócitos/metabolismo , Sistema de Sinalização das MAP Quinases , Molécula 1 de Adesão de Célula Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator 2 Ativador da Transcrição/genética , Movimento Celular , Proliferação de Células , Expressão Gênica , Humanos , Fosforilação , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Molécula 1 de Adesão de Célula Vascular/genética , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Vascular endothelial growth factor A (VEGF-A) is an essential cytokine that regulates endothelial function and angiogenesis. VEGF-A binding to endothelial receptor tyrosine kinases such as VEGFR1 and VEGFR2 triggers cellular responses including survival, proliferation and new blood vessel sprouting. Increased levels of a soluble VEGFR1 splice variant (sFlt-1) correlate with endothelial dysfunction in pathologies such as pre-eclampsia; however the cellular mechanism(s) underlying the regulation and function of sFlt-1 are unclear. Here, we demonstrate the existence of a biphasic stress response in endothelial cells, using serum deprivation as a model of endothelial dysfunction. The early phase is characterized by a high VEGFR2:sFlt-1 ratio, which is reversed in the late phase. A functional consequence is a short-term increase in VEGF-A-stimulated intracellular signaling. In the late phase, sFlt-1 is secreted and deposited at the extracellular matrix. We hypothesized that under stress, increased endothelial sFlt-1 levels reduce VEGF-A bioavailability: VEGF-A treatment induces sFlt-1 expression at the cell surface and VEGF-A silencing inhibits sFlt-1 anchorage to the extracellular matrix. Treatment with recombinant sFlt-1 inhibits VEGF-A-stimulated in vitro angiogenesis and sFlt-1 silencing enhances this process. In this response, increased VEGFR2 levels are regulated by the phosphatidylinositol-3-kinase and PKB/Akt signaling pathways and increased sFlt-1 levels by the ERK1/2 signaling pathway. We conclude that during serum withdrawal, cellular sensing of environmental stress modulates sFlt-1 and VEGFR2 levels, regulating VEGF-A bioavailability and ensuring cell survival takes precedence over cell proliferation and migration. These findings may underpin an important mechanism contributing to endothelial dysfunction in pathological states.