Antenatal antiarrhythmic treatment for fetal tachyarrhythmias: a study protocol for a prospective multicentre trial

Introduction Several retrospective or single-centrestudies demonstrated the efficacy of transplacentaltreatment of fetal tachyarrhythmias. Our retrospectivenationwide survey showed that the fetal therapy willbe successful at an overall rate of 90%. For fetuseswith hydrops, the treatment success rate will be 80%.However, standard protocol has not been established.The objective of this study is to evaluate the efficacy andsafety of the protocol-defined transplacental treatment offetal tachyarrhythmias. Participant recruitment began inOctober 2010.Methods and analysis The current study is a multicentre,single-arm interventional study. A total of 50 fetuseswill be enrolled from 15 Japanese institutions. Theprotocol-defined transplacental treatment is performed forsingletons with sustained fetal tachyarrhythmia ≥180 bpm,with a diagnosis of supraventricular tachycardia or atrialflutter. Digoxin, sotalol, flecainide or a combination is usedfor transplacental treatment. The primary endpoint isdisappearance of fetal tachyarrhythmias. The secondaryendpoints are fetal death related to tachyarrhythmia,proportion of preterm birth, rate of caesarean sectionattributable to fetal arrhythmia, improvement in fetalhydrops, neonatal arrhythmia, neonatal central nervoussystem disorders and neonatal survival. Maternal, fetal andneonatal adverse events are evaluated at 1 month afterbirth. Growth and development are also evaluated at 18and 36 months of corrected age.Ethics and dissemination The Institutional Review Boardof the National Cerebral and Cardiovascular Center ofJapan has approved this study. Our findings will be widelydisseminated through conference presentations and peerreviewedpublications

Drosophila Embryonic Hemocytes Produce Laminins to Strengthen Migratory Response

Summary: The most prominent developmental function attributed to the extracellular matrix (ECM) is cell migration. While cells in culture can produce ECM to migrate, the role of ECM in regulating developmental cell migration is classically viewed as an exogenous matrix presented to the moving cells. In contrast to this view, we show here that Drosophila embryonic hemocytes deposit their own laminins in streak-like structures to migrate efficiently throughout the embryo. With the help of transplantation experiments, live microscopy, and image quantification, we demonstrate that autocrine-produced laminin regulates hemocyte migration by controlling lamellipodia dynamics, stability, and persistence. Proper laminin deposition is regulated by the RabGTPase Rab8, which is highly expressed and required in hemocytes for lamellipodia dynamics and migration. Our results thus support a model in which, during embryogenesis, the Rab8-regulated autocrine deposition of laminin reinforces directional and effective migration by stabilizing cellular protrusions and strengthening otherwise transient adhesion states. : The role of ECM in regulating developmental cell migration is classically viewed as an exogenous matrix presented to moving cells. In contrast, using the fruit fly, Sánchez-Sánchez et al. show that Drosophila embryonic hemocytes use autocrine-produced laminins to regulate lamellipodia stability, dynamics, and persistence, thus reinforcing directional migration. Keywords: cell migration, laminins, hemocytes, Drosophila, lamellipodia dynamics, extracellular matri

The Caenorhabditis elegans microtubule minus-end binding homolog PTRN-1 stabilizes synapses and neurites

Microtubule dynamics facilitate neurite growth and establish morphology, but the role of minus-end binding proteins in these processes is largely unexplored. CAMSAP homologs associate with microtubule minus-ends, and are important for the stability of epithelial cell adhesions. In this study, we report morphological defects in neurons and neuromuscular defects in mutants of the C. elegans CAMSAP, ptrn-1. Mechanosensory neurons initially extend wild-type neurites, and subsequently remodel by overextending neurites and retracting synaptic branches and presynaptic varicosities. This neuronal remodeling can be activated by mutations known to alter microtubules, and depends on a functioning DLK-1 MAP kinase pathway. We found that PTRN-1 localizes to both neurites and synapses, and our results suggest that alterations of microtubule structures caused by loss of PTRN-1 function activates a remodeling program leading to changes in neurite morphology. We propose a model whereby minus-end microtubule stabilization mediated by a functional PTRN-1 is necessary for morphological maintenance of neurons. DOI: http://dx.doi.org/10.7554/eLife.01637.00

Expression of ADAMTS-8, a secreted protease with antiangiogenic properties, is downregulated in brain tumours

Angiogenesis and extracellular matrix degradation are key events in tumour progression, and factors regulating stromal–epithelial interactions and matrix composition are potential targets for the development of novel anti-invasive/antiangiogenic therapies. Here, we examine the expression of ADAMTS-8, a secreted protease with antiangiogenic properties, in brain tissues. Using quantitative RT–polymerase chain reaction (PCR), high, equivalent expression of ADAMTS-8 was found in normal whole brain, cerebral cortex, frontal lobe, cerebellum and meninges. ADAMTS-8 expression in 34 brain tumours (including 22 high-grade gliomas) and four glioma cell lines indicated at least two-fold reduction in mRNA compared to normal whole brain in all neoplastic tissues, and no detectable expression in 14 out of 34 (41%) tumours or four out of four (100%) cell lines. In contrast, differential expression of TSP1 and VEGF was seen in nine out of 15 (60%) and seven out of 13 (54%) tumours, with no relationship in the expression of these genes. Immunohistochemistry and Western analysis indicated downregulation of ADAMTS-8 protein in >77% tumours. Methylation-specific PCR analysis of ADAMTS-8 indicated promoter hypermethylation in one out of 24 brain tumours (a metastasis) and three out of four glioma cell lines suggesting an alternative mechanism of downregulation. These data suggest a role for ADAMTS-8 in brain tumorigenesis, warranting further investigation into its role in regulation of tumour angiogenesis and local invasion

Human U87 Astrocytoma Cell Invasion Induced by Interaction of βig-h3 with Integrin α5β1 Involves Calpain-2

It is known that βig-h3 is involved in the invasive process of many types of tumors, but its mechanism in glioma cells has not been fully clarified. Using immunofluorescent double-staining and confocal imaging analysis, and co-immunoprecipitation assays, we found that βig-h3 co-localized with integrin α5β1 in U87 cells. We sought to elucidate the function of this interaction by performing cell invasion assays and gelatin zymography experiments. We found that siRNA knockdowns of βig-h3 and calpain-2 impaired cell invasion and MMP secretion. Moreover, βig-h3, integrins and calpain-2 are known to be regulated by Ca2+, and they are also involved in tumor cell invasion. Therefore, we further investigated if calpain-2 was relevant to βig-h3-integrin α5β1 interaction to affect U87 cell invasion. Our data showed that βig-h3 co-localized with integrin α5β1 to enhance the invasion of U87 cells, and that calpain-2, is involved in this process, acting as a downstream molecule

Trust or not to trust: Analyzing the effect of social media influencers on the consumer purchase intention mediated by consumer attitude

This study aimed to investigate how social media influencers influence consumer buying behavior in Metro Manila. Influencer marketing has become an effective advertising strategy for brands and companies to promote their products through individuals who are recognized for their knowledge and content in a particular industry. The study focused on two types of influencers, Macro and Micro, to understand their impact on consumer buying intentions and how it was affected by the attitudes of individuals living in Metro Manila. The study used the convenience sampling technique for a total sample size of 385 respondents who are convenient and available to take the survey. The study used the source credibility model and para-social relationships to analyze the impact of social media influencers on consumer purchase intentions. The correlational and regression analysis conducted on the relationship between Social Media Influencer and Consumer Purchase Intention provided evidence that Social Media Influencers had a significant positive impact on consumer behavior. The analysis also revealed that the sub-variables of Social Media Influencers (Relevance, Resonance, and Reach) played an important role in shaping consumer behavior. The results of the study suggested that social media influencers played an important role in shaping consumer behavior, and businesses could leverage their power to improve customer acquisition and retention strategies. The study found that consumer attitudes acted as a mediator in the relationship between social media influencers and consumer purchase intention. The findings highlighted the importance of considering consumer attitudes as a factor in understanding the impact of social media influencers on consumer behavior. The results of this study would be beneficial for businesses and marketers in creating effective marketing strategies using social media influencers

Tailor-made circulatory management based on the stress–velocity relationship in preterm infants

Preterm infants frequently experience pulmonary hemorrhage or cerebral intraventricular hemorrhage after birth. The immature myocardium of the left ventricle faces a high afterload after the baby is separated from the placenta. However, the preterm left ventricle has limited ability to respond to such an increase in afterload. This results in depressed cardiac function and a deterioration in hemodynamics. We speculated that the perinatal deterioration in cardiac performance would be closely related to serious hemorrhages. To prove our hypothesis, we studied the interrelationship between the perinatal changes in cardiac performance and the incidences of intraventricular and pulmonary hemorrhage. We obtained the stress–velocity relationship (rate-corrected mean fiber shortening velocity and end-systolic wall stress relationship) by M-mode echocardiography and arterial blood pressure measurement. We found that the incidences of intraventricular and/or pulmonary hemorrhages were higher in infants with an excessive afterload, which resulted in a decrease in the function of the left ventricle. We suggest that careful attention to keep the afterload at an acceptable level by vasodilator therapy and sedation may reduce or prevent these serious complications. In this review, we will discuss our data along with related literature