Chronic mild stress leads to anxiety-like behavior and decreased p70 S6K1 activity in the hippocampus of male mice.

Major affective disorders are highly prevalent, however, current treatments are limited in their effectiveness due to a lack of understanding of underlying molecular mechanisms. Recent studies have shown that reduced activity of p70 S6 kinase 1 (S6K1), a downstream target of the mechanistic target of rapamycin complex 1 (mTORC1), is linked to anxiety-like behavior in both humans and rodents. The purpose of this study was to investigate the relationship between S6K1 and anxiety-like behavior following chronic mild stress (CMS) and drug-induced inhibition of S6K1. Following CMS, anxiety-like behavior was evaluated using an open field (OF) and elevated plus maze (EPM) in adult male C57/Bl6 mice. After behavior analysis, samples of the hippocampus were harvested for quantification of S6K1, S6 ribosomal protein, glycogen synthase kinase-3 ß (GSK3ß), and beta tubulin via western blot. Our results demonstrate that CMS mice exhibit anxiety-like behavior in the OF and EPM and reduced activity of S6K1 in the hippocampus (HPC). We measured phosphorylation levels of GSK3ß and found that GSK3ß phosphorylation was also reduced following CMS compared to control mice. Furthermore, pharmacological inhibition of S6K1 with PF-4708671 in male mice was sufficient to produce anxiety-like behavior in the OF and EPM. These results further support the significant role of S6K1 in the pathogenesis of anxiety and affective disorders.

Comparison of Visual Outcome After Hyperopic LASIK Using a Wavefront-Optimized Platform Versus Other Excimer Lasers in the Past Two Decades.

INTRODUCTION: Laser-assisted in-situ keratomileusis (LASIK) for the correction of hyperopia and hyperopic astigmatism is challenging and has been less studied than for the correction of myopia and myopic astigmatism. The aim of this study was to analyze the refractive outcomes of LASIK in hyperopia and hyperopic astigmatic eyes using a wave-front optimized laser platform (the Allegretto EX500 laser) and perform a historical comparison with other excimer lasers within the past two decades. METHODS: A one-center (Tertiary Refractive Center, Draper, Utah), retrospective, non-comparative study was conducted on 379 eyes treated with LASIK for hyperopia and hyperopic astigmatism. The data retrieved on these eyes were analyzed using uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and spherical equivalents. A literature search of excimer platforms in use in the past 20 years and a comparison of US Federal Drug Administration-approved platforms for hyperopia were performed. RESULTS: At 3 and 12 months postoperatively, 142 (66%) and 81 (69%) eyes had a UDVA of 20/20 or better and 207 (96%) and 114 (97%) eyes had a UDVA of 20/40 or better, respectively. The mean refractive spherical equivalent was - 0.52 ± 0.78 D at 3 months and - 0.46 ± 0.79 D at 12 months. At 12 months, 181 (96%) eyes achieved a spherical equivalent within ± 1.00 D of the intended target. Studies published before 2005 reported lower rates of UDVA 20/20 or better (32%) compared to those published after (68%); however, this discrepancy was less evident for UDVA 20/40 or better. A similar trend towards improved accuracy was noted in the literature with postoperative manifest refractive spherical equivalent within ± 0.50 D before and after 2005. CONCLUSION: There has been significant improvement in safety, efficacy, stability, and accuracy of LASIK treatment for hyperopia and hyperopic astigmatism within the past two decades. Newer excimer lasers meet industry standards and in particular, the Allegretto EX500 used in this study exceeded industry standards.