Ranibizumab ± laser therapy resulted in similar rates (∼40%) of suboptimal (<5-letter) and pronounced (≥10-letter) BCVA improvement at 12 weeks. Eyes with suboptimal early BCVA response showed poorer long-term visual outcomes than eyes with pronounced early response (mean improvement 3.0 vs 13.8 letters at 156 weeks).
: Objective: The objective was to examine the association between mobile media device use and communication delays in 18-month-old children. Methods: A cross-sectional study was conducted from September 2011 and December 2015 within the TARGet Kids! primary care research network. Children were included if parents reported their child's mobile media device use and completed a validated questionnaire for communication delay at the 18-month well child visit. Mobile media device use was measured using a parent-reported survey instrument. Daily mobile media device use was calculated as a weighted average of typical weekday and weekend day mobile media device use. Two communication outcomes were investigated: (1) expressive speech delay and (2) other communication delays, as measured by the Infant Toddler Checklist. Results: The study sample included 893 children (mean age 18.7 months, 54.1% male). Most parents reported 0 minutes per day of mobile media device use in their children (n = 693, 77.6%). Among children whose parents reported any mobile media device use (n = 200, 22.4%), the median daily mobile media device use was 15.7 minutes (range 1.4–300). The prevalence of parent-reported expressive speech delay was 6.6%, and the prevalence of other parent-reported communication delays was 8.8%. For children who used a mobile media device, each additional 30-minute increase in daily mobile media device use was associated with increased odds of parent-reported expressive speech delay (OR a = 2.33, 95% confidence interval, 1.25–4.82). No relationship was observed between mobile media device use and other parent-reported communication delays. Conclusion: Our study demonstrated a significant association between mobile media device use and parent-reported expressive speech delay in 18-month-old children.
Stimulator of interferon genes (STING) is an endoplasmic reticulum transmembrane protein that serves as a molecular hub for activation of interferon and inflammatory cytokine response by multiple cellular DNA sensors. Not surprisingly, STING has been demonstrated to play an important role in host defense against microorganisms and pharmacologic activation of STING is considered as an attractive strategy to treat viral diseases and boost antitumor immunity. In light of this we established a HepAD38-derived reporter cell line that expresses firefly luciferase in response to the activation of cyclic GMP-AMP synthase (cGAS)-STING pathway for high throughput screening (HTS) of small molecular human STING agonists. This cell-based reporter assay required only 4 h treatment with a reference STING agonist to induce a robust luciferase signal and was demonstrated to have an excellent performance in HTS format. By screening 16,000 compounds, a dispiro diketopiperzine (DSDP) compound was identified to induce proinflammatory cytokine response in a manner dependent on the expression of functional human STING, but not mouse STING. Moreover, we showed that DSDP induced an interferon-dominant cytokine response in human skin fibroblasts and peripheral blood mononuclear cells, which in turn potently suppressed the replication of yellow fever virus, dengue virus and Zika virus. We have thus established a robust cell-based assay system suitable for rapid discovery and mechanistic analyses of cGAS-STING pathway agonists. Identification of DSDP as a human STING agonist enriches the pipelines of STING-targeting drug development for treatment of viral infections and cancers.
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