Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

The significance of storytelling in primary schools in Cambodia : setting goals for the next five-year plan

This study has been conducted in order to understand how Cambodian teachers and librarians who implement storytelling in their primary schools and principals as supervisors define the benefits and the disadvantages of storytelling for education. Survey questionnaires were collected from 151 teachers, librarians, and school principals in two provinces of Cambodia. Data analysis revealed five main advantages of storytelling: 1) knowledge and language acquisition, 2) increase of internal education efficiency, 3) preservation of culture and tradition, 4) imagination development, and 5) moral development through analysis of stories, and found two disadvantages, 1) a lack of insight and attention and, 2) a lack of teachers\u27 storytelling skills. Interview respondents mentioned that the problem is related to low storytelling and story selection skills of storytellers. Based on the results, the Shanti Volunteer Association (SVA) will revise its project objectives and redesign its future storytelling program and teacher training. These findings will also be shared with the Ministry of Education, Youth, and Sports in Cambodia as it reviews its objectives for a storytelling hour in the primary education curriculum

The significance of storytelling in primary schools in Cambodia : setting goals for the next five-year plan

This study has been conducted in order to understand how Cambodian teachers and librarians who implement storytelling in their primary schools and principals as supervisors define the benefits and the disadvantages of storytelling for education. Survey questionnaires were collected from 151 teachers, librarians, and school principals in two provinces of Cambodia. Data analysis revealed five main advantages of storytelling: 1) knowledge and language acquisition, 2) increase of internal education efficiency, 3) preservation of culture and tradition, 4) imagination development, and 5) moral development through analysis of stories, and found two disadvantages, 1) a lack of insight and attention and, 2) a lack of teachers\u27 storytelling skills. Interview respondents mentioned that the problem is related to low storytelling and story selection skills of storytellers. Based on the results, the Shanti Volunteer Association (SVA) will revise its project objectives and redesign its future storytelling program and teacher training. These findings will also be shared with the Ministry of Education, Youth, and Sports in Cambodia as it reviews its objectives for a storytelling hour in the primary education curriculum

Structure and Function of the PB1 Domain, a Protein Interaction Module Conserved in Animals, Fungi, Amoebas, and Plants

Proteins containing the PB1 domain, a protein interaction module conserved in animals, fungi, amoebas, and plants, participate in diverse biological processes. The PB1 domains adopt a ubiquitin-like β-grasp fold, containing two α helices and a mixed five-stranded β sheet, and are classified into groups harboring an acidic OPCA motif (type I), the invariant lysine residue on the first β strand (type II), or both (type I/II). The OPCA motif of a type I PB1 domain forms salt bridges with basic residues, especially the conserved lysine, of a type II PB1 domain, thereby mediating a specific PB1-PB1 heterodimerization, whereas additional contacts contribute to high affinity and specificity of the modular interaction. The canonical PB1 dimerization is required for the formation of complexes between p40phox and p67phox (for activation of the NADPH oxidase crucial for mammalian host defense), between the scaffold Bem1 and the guanine nucleotide exchange factor Cdc24 (for polarity establishment in yeasts), and between the polarity protein Par6 and atypical protein kinase C (for cell polarization in animal cells), as well as for the interaction between the mitogen-activated protein kinase kinase kinases MEKK2 or MEKK3 and the downstream target mitogen-activated protein kinase kinase MEK5 (for early cardiovascular development in mammals). PB1 domains can also mediate interactions with other protein domains. For example, an intramolecular interaction between the PB1 and PX domains of p40phox regulates phagosomal targeting of the microbicidal NADPH oxidase; the PB1 domain of MEK5 is likely responsible for binding to the downstream kinase ERK5, which lacks a PB1 domain; and the scaffold protein Nbr1 associates through a PB1-containing region with titin, a sarcomere protein without a PB1 domain. This Review describes various aspects of PB1 domains at the molecular and cellular levels