ABSTRACT
The Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) was developed more than 25 years ago as an instrument to monitor functional change over time in patients with ALS. It has since been revised and extended to meet the needs of high data quality in ALS trials (ALSFRS-R), however a full re-validation of the scale was not completed. Despite this, the scale has remained a primary outcome measure in clinical trials. We convened a group of clinical trialists to discuss and explore opportunities to improve the scale and propose alternative measures. In this meeting report, we present a call to action on the use of the ALSFRS-Revised scale in clinical trials, focusing on the need for (1) harmonization of the ALSFRS-R administration globally, (2) alignment on a set of recommendations for clinical trial design and statistical analysis plans (SAPs), and (3) use of additional outcome measures.
Subject(s)
Amyotrophic Lateral Sclerosis , Humans , Amyotrophic Lateral Sclerosis/diagnosis , Amyotrophic Lateral Sclerosis/drug therapy , Severity of Illness Index , Disease ProgressionABSTRACT
A training and coaching team embarked on a training and technical assistance program evaluation project to examine the development of a tool used to determine the impact of training on staff and families serving youth with behavioral health challenges and their families. The training evaluation project centered on the development of a tool to examine the impact of training on trainee attitudes. The current article provides an overview of the development of the Nurtured Heart Approach® (NHA) Questionnaire to help support training and technical assistance implementation efforts by nursing and other trainers interested in best practice approaches to empower youth with behavioral health challenges. The questionnaire was found to be internally consistent and to have relatively stable, empirically derived factors consistent with the NHA model, but differing somewhat from the theoretically derived "Stands," or areas of emphasis. The questionnaire is sensitive to changes in attitude resulting from the NHA training. Therefore, it would a viable, practical instrument to test staff acquisition of NHA-related attitudes. [Journal of Psychosocial Nursing and Mental Health Services, 60(2), 15-19.].
Subject(s)
Mental Health Services , Adolescent , Humans , Program Evaluation , Surveys and QuestionnairesABSTRACT
Xenopus Aurora-A (also known as Eg2) is a member of the Aurora family of mitotic serine/threonine kinases. In Xenopus oocytes, Aurora-A phosphorylates and activates a cytoplasmic mRNA polyadenylation factor (CPEB) and therefore plays a pivotal role in MOS translation. However, hyperphosphorylation and activation of Aurora-A appear to be dependent on maturation-promoting factor (MPF) activation. To resolve this apparent paradox, we generated a constitutively activated Aurora-A by engineering a myristylation signal at its N terminus. Injection of Myr-Aurora-A mRNA induced germinal vesicle breakdown (GVBD) with the concomitant activation of MOS, mitogen-activated protein kinase, and MPF. Myr-Aurora-A-injected oocytes, however, appeared to arrest in meiosis I with high MPF activity and highly condensed, metaphase-like chromosomes but no organized microtubule spindles. No degradation of CPEB or cyclin B2 was observed following GVBD in Myr-Aurora-A-injected oocytes. In the presence of progesterone, the endogenous Aurora-A became hyperphosphorylated and activated at the time of MPF activation. Following GVBD, Aurora-A was gradually dephosphorylated and inactivated before it was hyperphosphorylated and activated again. This biphasic pattern of Aurora-A activation mirrored that of MPF activation and hence may explain meiosis I arrest by the constitutively activated Myr-Aurora-A.
Subject(s)
Cell Cycle Proteins , Protein Kinases/metabolism , Animals , Aurora Kinases , Cyclin B/metabolism , DNA, Complementary/metabolism , Enzyme Activation , Enzyme Inhibitors/pharmacology , Fluorescence Resonance Energy Transfer , Immunoblotting , MAP Kinase Signaling System , Meiosis , Microscopy, Confocal , Mitosis , Myristic Acid/metabolism , Oocytes/metabolism , Phosphorylation , Protein Biosynthesis , Protein Serine-Threonine Kinases , Protein Structure, Tertiary , RNA, Messenger/metabolism , Schizosaccharomyces pombe Proteins/metabolism , Signal Transduction , Time Factors , Xenopus , Xenopus ProteinsABSTRACT
Several recent studies have demonstrated that insulin-like growth factor (IGF)-1-induced mitogen-activated protein kinase (MAP kinase) activation is abolished by pertussis toxin, suggesting that trimeric G proteins of the G(i) class are novel cellular targets of the IGF-1 signaling pathway. We report here that the intracellular domain of the Xenopus IGF-1 receptor is capable of binding to the Xenopus homolog of mammalian GIPC, a PDZ domain-containing protein previously identified as a binding partner of G(i)-specific GAP (RGS-GAIP). Binding of xGIPC to xIGF-1 receptor is independent of the kinase activity of the receptor and appears to require the PDZ domain of xGIPC. Injection of two C-terminal truncation mutants that retained the PDZ domain blocked IGF-1-induced Xenopus MAP kinase activation and oocyte maturation. While full-length xGIPC injection did not significantly alter insulin response, it greatly enhanced human RGS-GAIP in stimulating the insulin response in frog oocytes. This represents the first demonstration that GIPC x RGS-GAIP complex acts positively in IGF-1 receptor signal transduction.
