(±) cis-Bisamido epoxides: A novel series of potent FXIII-A inhibitors.

A novel class of potent FXIII-A inhibitors containing a (±) cis-bisamido epoxide pharmacophore is described. The compounds display highly potent inhibition of FXIII-A (IC50 = 5-500 nM) in an in vitro assay. In contrast to other types of previously described covalent transglutaminase inhibitors, the bis-amido epoxides exhibited no measurable reactivity with glutathione, therefore possibly rendering this class of compounds suitable for future in vivo investigations. Additionally, the compounds show selective inhibition for FXIII-A against the cysteine protease, cathepsin S although they proved to have similar potency with a closely related transglutaminase, TGII, to that observed for FXIII-A.

A nurse's role in promoting social capital in children and young people.

Enabling children's wellbeing by supporting their social networks is an important role of children's nurses. This article presents the concept of social capital as a cognitive tool to help nurses reflect on why and how supporting these networks is important. Through three case studies the authors introduce the attributes of social capital and how these may be applied and inform practice in hospital and community healthcare settings.

Percutaneous device closure of atrial septal defect results in very early and sustained changes of right and left heart function.

OBJECTIVES: To investigate the echocardiographic effects of percutaneous closure of secundum atrial septal defect (ASD) in adults and assess which pre-closure parameters predict good response to closure. BACKGROUND: ASD is a common congenital heart disease often undiscovered until adulthood. ASD closure has been revolutionized by the use of percutaneous devices. The effects of these procedures on echocardiographic parameters are not well characterized. METHODS: Patients undergoing percutaneous device closure of ASD between June 2007 and June 2009 had 3 sequential echocardiograms reviewed: pre-procedure, immediate post-procedure (24 hours) and 6-8 weeks post-procedure. Significant changes from baseline were investigated using paired t-test/1-way ANOVA. Pearson correlation (2-tailed) tests were used to categorize patients as 'good responders' to closure in terms of selected parameters. RESULTS: 129 echocardiograms in 43 consecutive patients were included. Remodeling of both ventricles occurred immediately following ASD closure and was sustained. Right ventricular (RV) diameter in diastole decreased by 13.5% and 19.3% compared to baseline at 24 hours and 6-8 weeks post-closure, respectively (p<0.05); Left ventricular (LV) diameter in diastole increased by 8.5% and 15.6%, respectively (p<0.05). Functional parameters of the RV also demonstrated early and sustained decreases (TAPSE decreased by 8.3% and 17% compared to baseline at 24 hours and 6-8 weeks post-closure, respectively (p<0.05)). Smaller RV baseline diameter appeared to predict good response to closure. CONCLUSIONS: Percutaneous ASD closure has immediate, sustained benefits on multiple echocardiographic parameters. Good responders have smaller RV at baseline, suggesting early closure is preferable.

Echocardiographic detection of atrial septal defects: the forgotten view.

The right parasternal view is conventionally used to assess the aortic valve and the ascending aorta. We describe two cases in which the right parasternal view was helpful in assessment of the interatrial septum and the detection of atrial septal defects (ASD), including one case in which this view confirmed the presence of a defect not seen in any other echocardiographic view. Use of the right parasternal view should be considered for assessment of the interatrial septum, particularly when there is a high index of suspicion for an atrial septal defect but no defect is seen on conventional views. It should also be used to exclude the possibility of multiple defects even when an ASD is visualized using conventional imaging planes.

The impact of exposure to domestic violence on children and young people: a review of the literature.

OBJECTIVE: This article reviews the literature concerning the impact of exposure to domestic violence on the health and developmental well-being of children and young people. Impact is explored across four separate yet inter-related domains (domestic violence exposure and child abuse; impact on parental capacity; impact on child and adolescent development; and exposure to additional adversities), with potential outcomes and key messages concerning best practice responses to children's needs highlighted. METHOD: A comprehensive search of identified databases was conducted within an 11-year framework (1995-2006). This yielded a vast literature which was selectively organized and analyzed according to the four domains identified above. RESULTS: This review finds that children and adolescents living with domestic violence are at increased risk of experiencing emotional, physical and sexual abuse, of developing emotional and behavioral problems and of increased exposure to the presence of other adversities in their lives. It also highlights a range of protective factors that can mitigate against this impact, in particular a strong relationship with and attachment to a caring adult, usually the mother. CONCLUSION: Children and young people may be significantly affected by living with domestic violence, and impact can endure even after measures have been taken to secure their safety. It also concludes that there is rarely a direct causal pathway leading to a particular outcome and that children are active in constructing their own social world. Implications for interventions suggest that timely, appropriate and individually tailored responses need to build on the resilient blocks in the child's life. PRACTICE IMPLICATIONS: This study illustrate the links between exposure to domestic violence, various forms of child abuse and other related adversities, concluding that such exposure may have a differential yet potentially deleterious impact for children and young people. From a resilient perspective this review also highlights range of protective factors that influence the extent of the impact of exposure and the subsequent outcomes for the child. This review advocates for a holistic and child-centered approach to service delivery, derived from an informed assessment, designed to capture a picture of the individual child's experience, and responsive to their individual needs.