RESUMEN
Fibroblast growth factor receptors (FGFRs) regulate diverse biological processes in eukaryotes. The nematode Caenorhabditis elegans is a good animal model for studying the roles of FGFR signaling and its mechanism of regulation. In this study, we report that KIN-9 is an FGFR homolog in C. elegans that plays essential roles in aging and stress response maintenance. kin-9 was discovered as a target of miR-246, a microRNA that is positively regulated by the Axin family member pry-1. We found that animals lacking kin-9 function were long-lived and resistant to chemically induced stress. Furthermore, they showed a reduced expression of endoplasmic reticulum unfolded protein response (ER-UPR) pathway genes, suggesting that kin-9 is required to maintain a normal ER-UPR. The analysis of GFP reporter-based expression in transgenic animals revealed that KIN-9 is localized in the intestine. Overall, our findings demonstrate that kin-9 is regulated by miR-246 and may function downstream of pry-1. This study prompts future investigations to understand the mechanism of miRNA-mediated FGFR function in maintaining aging and stress response processes.
RESUMEN
OBJECTIVE: To determine if comorbidities and high-risk medications affect the frequency of family physician visits among older patients. DESIGN: Retrospective chart review. SETTING: Academic family health team at Sunnybrook Health Sciences Centre in Toronto, Ont. PARTICIPANTS: Among patients aged 65 years and older who were registered patients of the family health team between July 1, 2013, and June 30, 2014, the 5% who visited their family physicians most frequently and the 5% who visited their family physicians least frequently were selected for the study (N = 265). MAIN OUTCOME MEASURES: Predictors of frequent visits to family physicians. RESULTS: The significant predictors of being a high-frequency user were female sex (odds ratio [OR] = 2.20, P = .03), age older than 85 years (OR = 5.35, P = .001), and higher total number of medications (OR = 1.49, P < .001). Age-adjusted Charlson comorbidity index score, number of Beers criteria medications, and Anticholinergic Risk Scale score were not significant predictors (P > .05). CONCLUSION: Female sex, age older than 85, and higher total number of medications were independent significant predictors of higher frequency of family physician visits among older patients. Validated tools, such as the Charlson comorbidity index, Beers criteria, and Anticholinergic Risk Scale, did not independently predict the frequency of visits, indicating that predicting frequency of visits is likely complex.