Background Previous studies of CF treatments have shown suboptimal adherence, though little has been reported regarding adherence patterns to ivacaftor. Electronic monitoring (EM) of adherence is considered a gold standard of measurement. Methods Adherence rates by EM were prospectively obtained and patterns over time were analyzed. EM-derived adherence rates were compared to pharmacy refill history and self-report. Results 12 subjects (age 6-48 years; CFTR-G551D mutation) previously prescribed ivacaftor were monitored for a mean of 118 days. Overall adherence by EM was 61%(SD=28%) and decreased over time. Median duration between doses was 16.9 hours (IQR 13.9-24.1 hours) and increased over time. There was no correlation between EM-derived adherence and either refill history (84%, r=0.26, p=0.42) or self-report (100%, r=0.40, p=0.22). Conclusions Despite the promising nature of ivacaftor, our data suggest adherence rates are suboptimal and comparable to other prescribed CF therapies, and more commonly used assessments of adherence may be unreliable.

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Background Circular RNA (circRNA) is emerging as an important player in human diseases, especially cancer. In our previous study, we identified a series of deregulated circRNAs in hepatocellular carcinoma (HCC) by performing circRNA microarray expression profile. Here, we aimed to explore the role of circ-LRIG3 (hsa_circ_0027345) in HCC. Methods qRT-PCR and western blot were used to asses gene and protein expression, respectively. CCK-8, EdU and Transwell assays were used to detect cell proliferation, migration and invasion. GSEA software was applied to analyze the pathway related to circ-LRIG3. Co-IP, RIP and ChIP assays were used to identify the positive feedback axis of circ-LRIG3/EZH2/STAT3. Animal study was carried to test the role of circ-LRIG3 in vivo. Results Circ-LRIG3 was notably upregulated in HCC and promoted HCC cell proliferation, migration, invasion and reduced apoptosis. Circ-LRIG3 formed a ternary complex with EZH2 and STAT3, facilitating EZH2-induced STAT3 methylation and subsequent phosphorylation, resulting in the activation of STAT3 signaling. In turn, activated STAT3 could directly bind to circ-LRIG3 promoter to increase circ-LRIG3 transcription activity, thus forming a positive feedback loop. The animal models showed that exogenous expression of circ-LRIG3 enhanced tumorigenicity and metastasis in vivo, whereas these effects were blocked after treatment with C188–9, a specific STAT3 small-molecule inhibitor. Clinically, high circ-LRIG3 was closely linked with aggressive clinicopathological features and was identified as an independent risk prognostic factor of overall survival. Importantly, plasma circ-LRIG3 was found to be a highly sensitive and specific non-invasive diagnostic indicator for HCC. Conclusions Our study reveals the carcinogenic role of circ-LRIG3 in HCC, which may provide a new therapeutic target for HCC patients.

Continuous anatomical and functional improvements can be observed after successful microinvasive macular hole surgery. The preoperative extent of the IS/OS junction defect is of good predictive value for postoperative macular sensitivity. However, the factors that influence BCVA are multiple. Prediction of BCVA based on a single anatomical parameter or assessment of macular function only based on BCVA should be avoided.

SIB-IMRT is a feasible therapeutic approach for esophageal carcinoma patients and provides encouraging locoregional control with a low toxicity profile. Further investigations should focus on dose escalation and optimization of the combination with systemic therapies.

Tea or green tea drinking was not associated with overall breast cancer risk, which may be masked by the differential effect in pre- and post-menopausal women.

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