A multivariable miRNA signature delineates the systemic hemodynamic impact of arteriovenous shunt placement in a pilot study

Arteriovenous (AV) fistulas for hemodialysis can lead to cardiac volume loading and increased serum brain natriuretic peptide (BNP) levels. Whether short-term AV loop placement in patients undergoing microsurgery has an impact on cardiac biomarkers and circulating microRNAs (miRNAs), potentially indicating an increased hemodynamic risk, remains elusive. Fifteen patients underwent AV loop placement with delayed free flap anastomosis for microsurgical reconstructions of lower extremity soft-tissue defects. N-terminal pro-BNP (NT-proBNP), copeptin (CT-proAVP), and miRNA expression profiles were determined in the peripheral blood before and after AV loop placement. MiRNA expression in the blood was correlated with miRNA expression from AV loop vascular tissue. Serum NT-proBNP and copeptin levels exceeded the upper reference limit after AV loop placement, with an especially strong NT-proBNP increase in patients with preexistent cardiac diseases. A miRNA signature of 4 up-regulated (miR-3198, miR-3127-5p, miR-1305, miR-1288-3p) and 2 down-regulated miRNAs (miR30a-5p, miR-145-5p) which are related to cardiovascular physiology, showed a significant systemic deregulation in blood and venous tissue after AV loop placement. AV loop placement causes serum elevations of NT-proBNP, copeptin as well as specific circulating miRNAs, indicating a potentially increased hemodynamic risk for patients with cardiovascular comorbidities, if free flap anastomosis is delayed

MicroRNA-regulated pathways of flow-stimulated angiogenesis and vascular remodeling in vivo

Background: Vascular shear stress promotes endothelial cell sprouting in vitro. The impact of hemodynamic forces on microRNA (miRNA) and gene expression within growing vascular networks in vivo, however, remain poorly investi‑ gated. Arteriovenous (AV) shunts are an established model for induction of neoangiogenesis in vivo and can serve as a tool for analysis of hemodynamic efects on miRNA and gene expression profles over time. Methods: AV shunts were microsurgically created in rats and explanted on postoperative days 5, 10 and 15. Neoan‑ giogenesis was confrmed by histologic analysis and micro-computed tomography. MiRNA and gene expression pro‑ fles were determined in tissue specimens from AV shunts by microarray analysis and quantitative real-time polymer‑ ase chain reaction and compared with sham-operated veins by bioinformatics analysis. Changes in protein expression within AV shunt endothelial cells were determined by immunohistochemistry. Results: Samples from AV shunts exhibited a strong overexpression of proangiogenic cytokines, oxygenationassociated genes (HIF1A, HMOX1), and angiopoetic growth factors. Signifcant inverse correlations of the expressions of miR-223-3p, miR-130b-3p, miR-19b-3p, miR-449a-5p, and miR-511-3p which were up-regulated in AV shunts, and miR-27b-3p, miR-10b-5p, let-7b-5p, and let-7c-5p, which were down-regulated in AV shunts, with their predicted interacting targets C–X–C chemokine receptor 2 (CXCR2), interleukin-1 alpha (IL1A), ephrin receptor kinase 2 (EPHA2), synaptojanin-2 binding protein (SYNJ2BP), forkhead box C1 (FOXC1) were present. CXCL2 and IL1A overexpression in AV shunt endothelium was confrmed at the protein level by immunohistochemistry. Conclusions: Our data indicate that fow-stimulated angiogenesis is determined by an upregulation of cytokines, oxygenation associated genes and miRNA-dependent regulation of FOXC1, EPHA2 and SYNJ2BP

MicroRNA-regulated pathways of flow-stimulated angiogenesis and vascular remodeling in vivo

Background: Vascular shear stress promotes endothelial cell sprouting in vitro. The impact of hemodynamic forces on microRNA (miRNA) and gene expression within growing vascular networks in vivo, however, remain poorly investigated. Arteriovenous (AV) shunts are an established model for induction of neoangiogenesis in vivo and can serve as a tool for analysis of hemodynamic effects on miRNA and gene expression profiles over time. Methods: AV shunts were microsurgically created in rats and explanted on postoperative days 5, 10 and 15. Neoangiogenesis was confirmed by histologic analysis and micro-computed tomography. MiRNA and gene expression profiles were determined in tissue specimens from AV shunts by microarray analysis and quantitative real-time polymerase chain reaction and compared with sham-operated veins by bioinformatics analysis. Changes in protein expression within AV shunt endothelial cells were determined by immunohistochemistry. Results: Samples from AV shunts exhibited a strong overexpression of proangiogenic cytokines, oxygenation-associated genes (HIF1A, HMOX1), and angiopoetic growth factors. Significant inverse correlations of the expressions of miR-223-3p, miR-130b-3p, miR-19b-3p, miR-449a-5p, and miR-511-3p which were up-regulated in AV shunts, and miR-27b-3p, miR-10b-5p, let-7b-5p, and let-7c-5p, which were down-regulated in AV shunts, with their predicted interacting targets C–X–C chemokine receptor 2 (CXCR2), interleukin-1 alpha (IL1A), ephrin receptor kinase 2 (EPHA2), synaptojanin-2 binding protein (SYNJ2BP), forkhead box C1 (FOXC1) were present. CXCL2 and IL1A overexpression in AV shunt endothelium was confirmed at the protein level by immunohistochemistry. Conclusions: Our data indicate that flow-stimulated angiogenesis is determined by an upregulation of cytokines, oxygenation associated genes and miRNA-dependent regulation of FOXC1, EPHA2 and SYNJ2BP

Interest groups in multiple streams:specifying their involvement in the framework

Although interests inhabit a central place in the multiple streams framework (MSF), interest groups have played only a minor role in theoretical and empirical studies until now. In Kingdon’s original conception, organized interests are a key variable in the politics stream. Revisiting Kingdon’s concept with a particular focus on interest groups and their activities—in different streams and at various levels—in the policy process, we take this argument further. In particular, we argue that specifying groups’ roles in other streams adds value to the explanatory power of the framework. To do this, we look at how interest groups affect problems, policies, and politics. The influence of interest groups within the streams is explained by linking the MSF with literature on interest intermediation. We show that depending on the number of conditions and their activity level, interest groups can be involved in all three streams. We illustrate this in case studies reviewing labor market policies in Germany and chemicals regulation at the European level

How important is a bike park visit for the overall tourist destination experience?

Tourism has become a highly competitive sector, forcing destinations to reinvent and constantly enhance extraordinary experiences in accordance with their miscellaneous destination characteristics, whilst considering mountain biking as a growing phenomenon. This study, therefore, aims at providing a general profile of bike park visitors and at identifying key success factors for a bike park in the context of a destination. A quantitative survey (n = 325) was conducted in a cross-sectional design. The results suggest differing types of visitors with diversified perceptions of a bike park’s key success factors related to the overall perception of sojourn satisfaction. This research extends the literature by (1) shedding light on a booming phenomenon and revealing profiles of bike-park tourists, (2) pointing out key success factors of a bike park and (3) providing information about the perceptions of a bike park related to the overall tourism destination

Influence of Varying Assessment Parameters on the Diagnostic Accuracy of Magnetic Resonance Imaging in the Local Staging of Prostate Cancer

INTRODUCTION There is a broad variability in the accuracy levels of MRI with regard to the local staging of prostate cancer (PCa). METHODS A prospective analysis was conducted in patients with localized PCa with MRI of the prostate before radical prostatectomy. MRI and pathology findings were independently reviewed and reported based on a standardized map of the prostate with 16 regions of interest (ROIs). Diagnostic accuracy analysis of the MRI was performed using varying prostate-subpart sizes and varying cutoffs for the radiological probability for PCa presence. RESULTS Seventy four patients were included. Using varying cutoff probabilities and varying sizes of prostate-subparts resulted in a broad range of sensitivity (6-88%) and specificity (38-100%). Lower probabilities of PCa presence and larger prostate-subparts resulted in higher sensitivity but lower specificity and vice versa. Best diagnostic performance was achieved by using prostate sextants and at least moderate probabilities for PCa presence; mean sensitivity and specificity were 38% (95% CI 13-75) and 95% (95% CI 88-98). CONCLUSION The use of varying assessment parameters strongly affects the diagnostic accuracy of MRI in the local staging of PCa. Hence, precise and standardized reporting regarding these parameters is important. In our study, using at least moderate probabilities for PCa presence on MRI and prostatic sextants as ROI size was associated with best diagnostic performance