Browsing by Author "Chan, Ryan K."

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    Exploring the Role of ATF4 in Circadian Photic Phase Shifting
    (2018-07-23) Chan, Ryan K.; Antle, Michael C.; Spanswick, Simon C.; Mychasiuk, Richelle; Epp, Jonathan Richard
    The phenotypic role of activation transcription factor 4 (ATF4) in the mammalian circadian system has yet to be characterized. Previous research has provided evidence that ATF4 may play a key role in modulating molecular circadian activity, and it has been hypothesized that it may also be important for modulating photic resetting of the clock as a repressor of CREB. The main objectives of this investigation were to characterize the circadian expression of ATF4 protein in different lighting conditions, and to examine if downregulation of ATF4 using small interfering RNA (siRNA) technology would significantly potentiate photic phase shifts. In the Syrian hamster, ATF4 appeared to have a circadian expression in a light/dark cycle, but not when animals were in constant darkness. Light sufficiently increased ATF4 protein expression 2-3hrs following light exposure suggesting light plays an important role in regulating ATF4 expression. However, downregulation of ATF4 via siATF4 did not significantly potentiate phase advances to light as hypothesized. Rather, injections of siATF4 appeared to significantly alter an animal’s phase angle of entrainment. In summary, ATF4 plays an important role in the rhythmicity of the clock as light appears to be important in driving ATF4 circadian expression and its downregulation resulted in increased phase angle. However, the function of light-induced ATF4 expression remains to be determined.
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    Prevalence and incidence of idiopathic subglottic stenosis in southern and central Alberta: a retrospective cohort study
    (2021-11-12) Chan, Ryan K.; Ahrens, Beau; MacEachern, Paul; Bosch, J. D.; Randall, Derrick R.
    Abstract Background Subglottic stenosis (SGS) is a reportedly rare disease that causes recurrent severe airway obstruction. Etiologies reported for SGS include idiopathic, iatrogenic, autoimmune, congenital, and traumatic, with variable ratios among different centres. From empiric observation, southern and central Alberta was hypothesized to have a disproportionate distribution of SGS driven by increased idiopathic SGS (iSGS) compared to previous literature. Identification of causative agents of iSGS will help understand and guide future management options, so this study aimed to characterize the demographics of SGS subtypes, define prevalence and incidence rates of iSGS in southern Alberta, and geographically analyze for clustering of iSGS prevalence. Methods SGS patients from Alberta census divisions No. 1–9 and 15 were retrospectively reviewed. Patients were subtyped according to etiology of SGS and characterized. Idiopathic SGS prevalence and incidence was assessed; prevalence was further geographically segregated by census division and forward sortation area (FSA). Significant clustering patterns were assessed for using a Global Moran’s I analysis. Results From 2010 to 2019 we identified 250 SGS patients, who were substantially overrepresented by idiopathic patients (80.4%) compared to autoimmune (10.0%), iatrogenic (7.6%), congenital (1.2%), and traumatic (0.8%). The total iSGS prevalence was 9.28/100,000 with a mean annual incidence rate of 0.71/100,000 per year. Significant clustering was observed (Moran’s index 0.125; z-score 2.832; p = 0.0046) and the highest rates of prevalence were observed in southern Alberta and in rural communities heterogeneously dispersed around Calgary FSAs. Conclusion In southern and central Alberta, iSGS patients were disproportionately over-represented in contrast to other subtypes with the highest prevalence in southern Alberta. There was a three-fold higher annual incidence compared to previous literature demonstrating the highest rates of disease reported worldwide. Future research aims to expand the geographical scope and to assess for demographic or environmental differences within significant clusters that may contribute to disease pathophysiology. Level of evidence III. Graphical Abstract