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Person-centered care concerns the values and perceptions of the patient in assessment of outcomes. Little is known about perceptions of adults with cerebral palsy (CP) concerning: the most important factors associated with quality of life, definitions of success, short- and long-term outcomes of childhood orthopedic care, and current needs for information surrounding childhood orthopedic care. An online survey gathered information using structured and semi-structured questions. Descriptive statistics and content analysis summarized findings of structured questions and comments. A total of 71 adults with CP (44 women, median age range 30–39 years), with a variety of functional abilities, participated in the study. Priorities for a good life were clustered. There existed two groups: achievement orientation and relationship orientation. Good health and interpersonal relationships were priorities for both groups. Definitions of success included happiness, independence, meaningful relationships/activities, and mindfulness/lifelong-learning. Fifty-eight percent perceived a positive impact of childhood orthopedic care on current function. A positive perception was associated with being included in the decision making process (chi-square 25, p <.001). Suggestions to improve childhood orthopedic care included: more information about long-term outcomes, surgical timing, and alternatives to surgery, and improved service delivery models to prevent gaps in care across the lifespan. Ongoing conversations about how improvements from orthopedic surgery in childhood may not last through adolescence or adulthood are needed. The importance of impairment-based interventions should be contextualized within needs for health promotion and social engagement long-term. More research is needed on cost-benefit of childhood orthopedic surgery. Perceptions of being included in decisions about surgery as a child was associated with long term satisfaction. Consumer education is needed about how improvements gained in childhood may not persist through adolescence or into adulthood. Individual priorities for quality of life vary; and these priorities should be considered when weighing the cost benefit ratio of interventions. Clinicians should broaden the conversation to include how orthopedic surgery and rehabilitation afterwards could potentially impact health and well being in the future. [ABSTRACT FROM AUTHOR]

The article addresses the implications of the Florida Supreme Court's ruling in Miller v. Alabama, which declared mandatory life sentences without parole for juveniles unconstitutional, on resentencing and future sentencing of juveniles convicted of murder and explores Florida's response as evidenced in Falcon v. State. Topics discussed are factors to imposing life sentence, juvenile sentencing factors mandated by the U.S. Supreme Court, and equal balance of rights between defendant and victim.

The dimerization of the G protein-coupled receptors for endothelin-1 (ET-1), endothelin A receptor (ETA) and endolethin B receptor (ETB), is well established. However, the signaling consequences of the homodimerization and heterodimerization of ETA and ETB is not well understood. Here, we demonstrate that peptides derived from the C-termini of these receptors regulate the signaling capacity of ET-1. The C-termini of the ETA and ETB receptors are believed to consist of three α-helices, which may serve as points of interaction between the receptors. The third α-helix in the C-terminus is of particular interest because of its amphipathic nature. In a cell line expressing only the ETA receptor, expression of residues Y430-S442, representing the third helix of the ETB C-terminus, leads to a dramatic increase in the signaling induced by ET-1. In contrast, in a cell line containing only ETB, Y430-S442 has an antagonistic effect, slightly reducing the ET-1 induced signal. Computational docking results suggest that the α-helical ETB-derived peptide binds to the second and third intracellular loops of the ETA receptor consistent with the alteration of its signaling capacity. Our results described here provide important insight into ETA/ETB receptor interactions and possibly a new approach to regulate specific G protein-coupled receptor signal transmission. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Migration of vascular smooth muscle cells is a key element in remodeling during pulmonary arterial hypertension (PAH). We are observing key alterations in the migratory characteristics of human pulmonary artery smooth muscle cells (HPASMC) isolated from transplanted lungs of subjects with PAH. Using wound migration and barrier removal assays, we demonstrate that the PAH cells migrate under quiescent growth conditions and in the absence of pro-migratory factors such as platelet derived growth factor (PDGF). Under the same conditions, in the absence of PDGF, non-PAH HPASMC show negligible migration. The dysregulated migration initiates, in part, through phosphorylation events signaled through the unstimulated PDGF receptor via focal adhesion kinase (FAK) whose total basal expression and phosphorylation at tyrosine 391 is markedly increased in the PAH cells and is inhibited by a motif mimicking cell-permeable peptide (MMCPP) targeting the Tyr751 region of the PDGF receptor and by imatinib. However, exposure of the PAH cells to PDGF further promotes migration. Inhibition of p21 activated kinases (PAK), LIM kinases (LIMK), c-Jun N-terminal kinases (JNK) and p38 mitogen-activated protein kinases (MAPK) reduces both the dysregulated and the PDGF-stimulated migration. Immunofluorescence microscopy confirms these observations showing activated JNK and p38 MAPK at the edge of the wound but not in the rest of the culture in the PAH cells. The upstream inhibitors FAK (PF-573228) and imatinib block this activation of JNK and p38 at the edge of the site of injury and correspondingly inhibit migration. MMCPP which inhibit the activation of downstream effectors of migration, cofilin and caldesmon, also limit the dysregulated migration. These results highlight key pathways which point to potential targets for future therapies of pulmonary hypertension with MMCPP.