Inhibition of MicroRNA-125a Promotes Human Endothelial Cell Proliferation and Viability through an Antiapoptotic Mechanism.

The microRNA-125a (miR-125a) is highly expressed in endothelial cells, but its role in vascular biology is not known. Endothelial cell proliferation and viability play an important role in endothelial healing, and we hypothesize that miR-125a regulates this process. The aim of the present study was to investigate if miR-125a controls human endothelial cell proliferation, viability and endothelial healing, and to assess the mechanisms involved. We showed that overexpression of miR-125a by transfection with miR-125a mimic reduced human umbilical vein endothelial cell (HUVEC) proliferation and viability, and stimulated apoptosis as demonstrated by a miR-125a-induced increase of the proportion of annexin V-positive cells monitored by flow cytometry. Moreover, we showed that the miR-125a mimic downregulated the antiapoptotic Bcl2 protein and upregulated caspase 3, suggesting that these two proteins represent molecular targets for miR-125a. Accordingly, transfection with miR-125a inhibitor, downregulating miR-125a expression, promoted HUVEC proliferation and viability, and reduced apoptosis. Importantly, transfection with miR-125a inhibitor promoted HUVEC tube formation in Matrigel, suggesting that reduction of miR-125a has a proangiogenic effect. In conclusion, downregulation of miR-125a through local transfection with miR-125a inhibitor might be a new way to enhance endothelial cell proliferation and viability, thereby promoting the reendothelialization observed in response to intimal injury. © 2014 S. Karger AG, Basel

Nanocomposites and polyethylene blends: two potentially synergistic strategies for HVDC insulation materials with ultra-low electrical conductivity

Among the various requirements that high voltage direct current (HVDC) insulation materials need to satisfy, sufficiently low electrical conductivity is one of the most important. The leading commercial HVDC insulation material is currently an exceptionally clean cross-linked low-density polyethylene (XLPE). Previous studies have reported that the DC-conductivity of low-density polyethylene (LDPE) can be markedly reduced either by including a fraction of high-density polyethylene (HDPE) or by adding a small amount of a well dispersed, semiconducting nanofiller such as Al2O3 coated with a silane. This study demonstrates that by combining these two strategies a synergistic effect can be achieved, resulting in an insulation material with an ultra-low electrical conductivity. The addition of both HDPE and C8–Al2O3 nanoparticles to LDPE resulted in ultra-insulating nanocomposites with a conductivity around 500 times lower than of the neat LDPE at an electric field of 32 kV/mm and 60–90 \ub0C. The new nanocomposite is thus a promising material regarding the electrical conductivity and it can be further optimized since the polyethylene blend and the nanoparticles can be improved independently

Regulation of smooth muscle dystrophin and synaptopodin 2 expression by actin polymerization and vascular injury

Producción CientíficaObjective: Actin dynamics in vascular smooth muscle is known to regulate contractile differentiation and may play a role in the pathogenesis of vascular disease. However, the list of genes regulated by actin polymerization in smooth muscle remains incomprehensive. Thus, the objective of this study was to identify actin-regulated genes in smooth muscle and to demonstrate the role of these genes in the regulation of vascular smooth muscle phenotype. Approach and Results: Mouse aortic smooth muscle cells were treated with an actin-stabilizing agent, jasplakinolide, and analyzed by microarrays. Several transcripts were upregulated including both known and previously unknown actin-regulated genes. Dystrophin and synaptopodin 2 were selected for further analysis in models of phenotypic modulation and vascular disease. These genes were highly expressed in differentiated versus synthetic smooth muscle and their expression was promoted by the transcription factors myocardin and myocardin-related transcription factor A. Furthermore, the expression of both synaptopodin 2 and dystrophin was significantly reduced in balloon-injured human arteries. Finally, using a dystrophin mutant mdx mouse and synaptopodin 2 knockdown, we demonstrate that these genes are involved in the regulation of smooth muscle differentiation and function. Conclusions: This study demonstrates novel genes that are promoted by actin polymerization, that regulate smooth muscle function, and that are deregulated in models of vascular disease. Thus, targeting actin polymerization or the genes controlled in this manner can lead to novel therapeutic options against vascular pathologies that involve phenotypic modulation of smooth muscle cells.Instituto de Salud Carlos III - Fondo Europeo de Desarrollo Regional (grant RD12/0042/0006)Ministerio de Economía, Industria y Competitividad (grants BFU2010-15898 and BFU2013-45867-R

Effects of a Synbiotic on Plasma Immune Activity Markers and Short-Chain Fatty Acids in Children and Adults with ADHD—A Randomized Controlled Trial

Synbiotic 2000, a pre + probiotic, reduced comorbid autistic traits and emotion dysregulation in attention deficit hyperactivity disorder (ADHD) patients. Immune activity and bacteria-derived short-chain fatty acids (SCFAs) are microbiota–gut–brain axis mediators. The aim was to investigate Synbiotic 2000 effects on plasma levels of immune activity markers and SCFAs in children and adults with ADHD. ADHD patients (n = 182) completed the 9-week intervention with Synbiotic 2000 or placebo and 156 provided blood samples. Healthy adult controls (n = 57) provided baseline samples. At baseline, adults with ADHD had higher pro-inflammatory sICAM-1 and sVCAM-1 and lower SCFA levels than controls. Children with ADHD had higher baseline sICAM-1, sVCAM-1, IL-12/IL-23p40, IL-2Rα, and lower formic, acetic, and propionic acid levels than adults with ADHD. sICAM-1, sVCAM-1, and propionic acid levels were more abnormal in children on medication. Synbiotic 2000, compared to placebo, reduced IL-12/IL-23p40 and sICAM-1 and increased propionic acid levels in children on medication. SCFAs correlated negatively with sICAM-1 and sVCAM-1. Preliminary human aortic smooth-muscle-cell experiments indicated that SCFAs protected against IL-1β-induced ICAM-1 expression. These findings suggest that treatment with Synbiotic 2000 reduces IL12/IL-23p40 and sICAM-1 and increases propionic acid levels in children with ADHD. Propionic acid, together with formic and acetic acid, may contribute to the lowering of the higher-than-normal sICAM-1 levels

Mapping registered nurse anaesthetists' intraoperative work: tasks, multitasking, interruptions and their causes, and interactions: a prospective observational study

Introduction Safe anaesthesia care is a fundamental part of healthcare. In a previous study, registered nurse anaesthetists (RNAs) had the highest task frequency, with the largest amount of multitasking and interruptions among all professionals working in a surgical team. There is a lack of knowledge on how these factors are distributed during the intraoperative anaesthesia care process, and what implications they might have on safety and quality of care. Objective To map the RNAs' work as done in practice, including tasks, multitasking, interruptions and their causes, and interactions, during all phases of the intraoperative anaesthesia work process. Methods Structured observations of RNAs (n=8) conducted during 30 procedures lasting a total of 73 hours in an operating department at a county hospital in Sweden, using the Work Observation Method By Activity Timing tool. Results High task intensity and multitasking were revealed during preparation for anaesthesia induction (79 tasks/hour, 61.9% of task time spent multitasking), anaesthesia induction (98 tasks/hour, 50.7%) and preparation for anaesthesia maintenance (86 tasks/hour, 80.2%). Frequent interruptions took place during preoperative preparation (4.7 /hour), anaesthesia induction (6.2 /hour) and preparation for anaesthesia maintenance (4.3 /hour). The interruptions were most often related to medication care (n=54, 19.8%), equipment issues (n=40, 14.7%) or the procedure itself (n=39, 14.3%). RNAs' work was conducted mostly independently (58.4%), but RNAs interacted with multiple professionals in and outside the operating room during anaesthesia. Conclusion The tasks, multitasking, interruptions and their causes, and interactions during different phases illustrated the RNAs' work as done, as part of a complex adaptive system. Management of safety in the most intense phases-preparing for anaesthesia induction, induction and preparing for anaesthesia maintenance-should be investigated further. The complexity and adaptivity of the nature of RNAs' work should be taken into consideration in future management, development, research and education.</p

A transcriptional timetable of autumn senescence

BACKGROUND: We have developed genomic tools to allow the genus Populus (aspens and cottonwoods) to be exploited as a full-featured model for investigating fundamental aspects of tree biology. We have undertaken large-scale expressed sequence tag (EST) sequencing programs and created Populus microarrays with significant gene coverage. One of the important aspects of plant biology that cannot be studied in annual plants is the gene activity involved in the induction of autumn leaf senescence. RESULTS: On the basis of 36,354 Populus ESTs, obtained from seven cDNA libraries, we have created a DNA microarray consisting of 13,490 clones, spotted in duplicate. Of these clones, 12,376 (92%) were confirmed by resequencing and all sequences were annotated and functionally classified. Here we have used the microarray to study transcript abundance in leaves of a free-growing aspen tree (Populus tremula) in northern Sweden during natural autumn senescence. Of the 13,490 spotted clones, 3,792 represented genes with significant expression in all leaf samples from the seven studied dates. CONCLUSIONS: We observed a major shift in gene expression, coinciding with massive chlorophyll degradation, that reflected a shift from photosynthetic competence to energy generation by mitochondrial respiration, oxidation of fatty acids and nutrient mobilization. Autumn senescence had much in common with senescence in annual plants; for example many proteases were induced. We also found evidence for increased transcriptional activity before the appearance of visible signs of senescence, presumably preparing the leaf for degradation of its components

Local inhibition of ornithine decarboxylase reduces vascular stenosis in a murine model of carotid injury

Objectives: Polyamines are organic polycations playing an essential role in cell proliferation and differentiation, as well as in cell contractility, migration and apoptosis. These processes are known to contribute to restenosis, a pathophysiological process often occurring in patients submitted to revascularization procedures. We aimed to test the effect of alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, on vascular cell pathophysiology in vitro and in a rat model of carotid arteriotomy-induced (re) stenosis. Methods: The effect of DFMO on primary rat smooth muscle cells (SMCs) and mouse microvascular bEnd. 3 endothelial cells (ECs) was evaluated through the analysis of DNA synthesis, polyamine concentration, cell viability, cell cycle phase distribution and by RT-PCR targeting cyclins and genes belonging to the polyamine pathway. The effect of DFMO was then evaluated in arteriotomy-injured rat carotids through the analysis of cell proliferation and apoptosis, RT-PCR and immunohistochemical analysis of differential gene expression. Results: DFMO showed a differential effect on SMCs and on ECs, with a marked, sustained anti-proliferative effect of DFMO at 3 and 8 days of treatment on SMCs and a less pronounced, late effect on bEnd. 3 ECs at 8 days of DFMO treatment. DFMO applied perivascularly in pluronic gel at arteriotomy site reduced subsequent cell proliferation and preserved smooth muscle differentiation without affecting the endothelial coverage. Lumen area in DFMO-treated carotids was 49% greater than in control arteries 4 weeks after injury. Conclusions: Our data support the key role of polyamines in restenosis and suggest a novel therapeutic approach for this pathophysiological process. (C) 2013 Elsevier Ireland Ltd. All rights reserved

Tasks, multitasking and interruptions among the surgical team in an operating room: a prospective observational study

Objectives: The work context of the operating room (OR) is considered complex and dynamic with high cognitive demands. A multidimensional view of the complete preoperative and intraoperative work process of the surgical team in the OR has been sparsely described. The aim of this study was to describe the type and frequency of tasks, multitasking, interruptions and their causes during surgical procedures from a multidimensional perspective on the surgical team in the OR.Design: Prospective observational study using the Work Observation Method By Activity Timing tool.Setting: An OR department at a county hospital in Sweden.Participants: OR nurses (ORNs) (n=10), registered nurse anaesthetists (RNAs) (n=8) and surgeons (n=9).Results: The type, frequency and time spent on specific tasks, multitasking and interruptions were measured. From a multidimensional view, the surgical team performed 64 tasks per hour. Communication represented almost half (45.7%) of all observed tasks. Concerning task time, direct care dominated the surgeons’ and ORNs’ intraoperative time, while in RNAs’ work, it was intra-indirect care. In total, 48.2% of time was spent in multitasking and was most often observed in ORNs’ and surgeons’ work during communication. Interruptions occurred 3.0 per hour, and the largest proportion, 26.7%, was related to equipment. Interruptions were most commonly followed by professional communication.Conclusions: The surgical team constantly dealt with multitasking and interruptions, both with potential impact on workflow and patient safety. Interruptions were commonly followed by professional communication, which may reflect the interactions and constant adaptations in a complex adaptive system. Future research should focus on understanding the complexity within the system, on the design of different work processes and on how teams meet the challenges of a complex adaptive system.</p