The i-ACT™ in Obesity educational intervention: a pilot study on improving Canadian family physician care in obesity medicine.

BACKGROUND: Obesity is a chronic problem in Canada and although the Canadian Medical Association recognizes obesity as a disease, health care professionals (HCPs) are not necessarily proactively managing it as one. This study aimed to assess current obesity management knowledge and practices of Canadian family physicians (FPs) and evaluate the feasibility of an online self-directed learning platform, i-ACT™ in Obesity, in delivering learning and changing practice intentions to advance obesity management. METHODS: i-ACT™ in Obesity is an online self-directed learning program designed by Canadian obesity medicine experts to provide individualized learning curricula to participants. One hundred FPs, with an interest in weight management and managing patients with obesity, were recruited across Canada to participate in a pilot study. FP education was delivered in a stepwise manner. Each participant completed a practice profile assessment to determine knowledge gaps and educational needs. Learners then watched didactic videos across disciplines on topics assigned to their curriculum by the program algorithm based on the relative difference between indicated and desired current knowledge. FPs also completed 10 retrospective patient assessments to assess clinical management practices and planned behaviour change. Feasibility, acceptability, and satisfaction of the learning program were assessed to formulate the rationale for a more widespread deployment in the future. Survey responses and related data were analyzed using comparative measures and descriptive statistics. RESULTS: The program was piloted by ninety-one Canadian FPs, where 900 patients were assessed. FPs showed distinct differences between their current and desired levels of comfort in a variety of obesity-related topics. Participation was associated with an intention to use more obesity treatment interventions moving forward. The program received an overall satisfaction rating of 8.6 out of 10 and 100% of the evaluators indicated that they would recommend it to their colleagues. CONCLUSION: The program was overall well received and successfully changed obesity management intentions among participating FPs, thus setting the stage for a larger more comprehensive study to examine the efficacy of i-ACT™ in Obesity in addressing knowledge gaps and advancing evidence-based, guidelines-aligned approach to obesity treatment.

Chloride intracellular channel 1 cooperates with potassium channel EAG2 to promote medulloblastoma growth.

Ion channels represent a large class of drug targets, but their role in brain cancer is underexplored. Here, we identify that chloride intracellular channel 1 (CLIC1) is overexpressed in human central nervous system malignancies, including medulloblastoma, a common pediatric brain cancer. While global knockout does not overtly affect mouse development, genetic deletion of CLIC1 suppresses medulloblastoma growth in xenograft and genetically engineered mouse models. Mechanistically, CLIC1 enriches to the plasma membrane during mitosis and cooperates with potassium channel EAG2 at lipid rafts to regulate cell volume homeostasis. CLIC1 deficiency is associated with elevation of cell/nuclear volume ratio, uncoupling between RNA biosynthesis and cell size increase, and activation of the p38 MAPK pathway that suppresses proliferation. Concurrent knockdown of CLIC1/EAG2 and their evolutionarily conserved channels synergistically suppressed the growth of human medulloblastoma cells and Drosophila melanogaster brain tumors, respectively. These findings establish CLIC1 as a molecular dependency in rapidly dividing medulloblastoma cells, provide insights into the mechanism by which CLIC1 regulates tumorigenesis, and reveal that targeting CLIC1 and its functionally cooperative potassium channel is a disease-intervention strategy.

The TRIM-NHL protein NHL-2 is a co-factor in the nuclear and somatic RNAi pathways in C. elegans.

Proper regulation of germline gene expression is essential for fertility and maintaining species integrity. In the C. elegans germline, a diverse repertoire of regulatory pathways promote the expression of endogenous germline genes and limit the expression of deleterious transcripts to maintain genome homeostasis. Here we show that the conserved TRIM-NHL protein, NHL-2, plays an essential role in the C. elegans germline, modulating germline chromatin and meiotic chromosome organization. We uncover a role for NHL-2 as a co-factor in both positively (CSR-1) and negatively (HRDE-1) acting germline 22G-small RNA pathways and the somatic nuclear RNAi pathway. Furthermore, we demonstrate that NHL-2 is a bona fide RNA binding protein and, along with RNA-seq data point to a small RNA independent role for NHL-2 in regulating transcripts at the level of RNA stability. Collectively, our data implicate NHL-2 as an essential hub of gene regulatory activity in both the germline and soma.