Activity

The relationship between the gas bubble and residual vitreous fluid showed a rapid shift when the patient’s head position changed. The MRI images demonstrated that with both 70% gas fill and 95% gas fill, lying on the side can give better support to the inferior retina than face-down positioning. The images demonstrated the importance of accurate head positioning, because a slight change in head position resulted in inadequate contact between the anterior inferior retina and the gas bubble. Conclusions To our knowledge, this is the first time that the relationship between an intraocular gas bubble and contact with the retina has been evaluated in different head positions in vivo using MRI imaging. The MRI images demonstrated that side positioning gives better contact between the gas bubble and the inferior and anterior retina than prone positioning even when the gas fill is only 70% of the vitreous cavity.Purpose To assess the impact of delaying anti-vascular endothelial growth factor (VEGF) treatment of active disease at any point during a patient’s treatment journey on clinical outcomes in a real-world cohort of patients with neovascular age-related macular degeneration (nAMD). Design Longitudinal cohort study. Participants Consecutive treatment-naive nAMD eyes commencing anti-VEGF monotherapy (bevacizumab, ranibizumab, or aflibercept) from January 2014 from a tertiary eye center in Singapore. Methods We conducted a real-world study using registry data comparing delayed re-treatment (defined as not receiving treatment at 2 or more monitoring visits when disease was graded as active) versus timely re-treatment (defined as receiving treatment when disease was active). Main outcome measures The primary outcome was the change in visual acuity (VA) in the timely and delayed re-treatment groups at 12 months. Results Data from 286 eyes were included and categorized into the timely (188 [66%]) or the delayed (98 ([34%]) group. The mean numbers of anti-VEGF injections over 12 months were similar 5.6 (standard deviation [SD], 2.9) versus 4.9 (SD, 3.2; P = 0.11) for the timely and delayed groups, respectively. Timely treated patients showed larger gains in VA (6.4 letters [SD, 8.1 letters] vs. 1.2 letters [SD, 5.3 letters; P = 0.04), a higher proportion with VA of 6/12 or better (30% vs. 8%; P = 0.01), and greater reduction in OCT-measured central subfield thickness (135 μm [SD, 154 μm] vs. 87.8 μm [SD, 129 μm]; P = 0.04) at 12 months. A longer delay between detection of active disease and re-treatment was associated with poorer vision outcomes (0.02-letter decrease/day; P = 0.03; R2 = 0.29). Conclusions Although it has been established that adequate numbers of injections are required for favorable outcomes, timely re-treatment of active disease also is important. This should be emphasized to patients to ensure optimal outcomes in real-world clinical settings.Piceatannol is a natural polyphenol compound found in passion fruit and blueberry with several biological activities. However, it is unclear whether piceatannol affects the activity of human UDP-glucuronosyltransferases (UGTs) enzymes. The present study aims to assess the potential inhibitory effect of piceatannol against UGTs enzymes, as well as to evaluate its potential food-drug interactions risk via UGTs inhibition. We systematically evaluated the inhibitory effects of piceatannol on UGTs using high-performance liquid chromatography by measuring the formation rates for 4-methylumbelliferoneglucuronide and imipramine N-glucuronide. The results indicated that piceatannol displayed broad-spectrum inhibition against human UGTs. Kinetic analysis showed that inhibition of piceatannol on UGT1A6 and UGT1A7 followed noncompetitive inhibition mechanism, while the inhibition on UGT1A8 and UGT1A9 obeyed competitive and mixed inhibition mechanism, respectively. The quantitative prediction of risks showed that the coadministration of piceatannol with drugs primarily cleared by UGT1A6, UGT1A7, UGT1A8, and UGT1A9 may result in potential food-drug interaction. In conclusion, additional caution should be taken when piceatannol and food containing piceatannol are co-administered with drugs metabolized by UGTs.Cardiotoxicity is an important toxicological endpoint for chemical and drug safety assessment. The present study aims to evaluate two stemcell-based in vitro models for cardiotoxicity screening of chemicals. Eleven model compounds were used to evaluate responses of mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs) using beating arrest as a readout and the analysis of electrophysiological parameters measured with a multi-electrode array (MEA) platform of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Results revealed that the hiPSC-CM MEA assay responded to all compounds. The mESC-CM beating arrest assay was not responsive to potassium channel blockers and showed a lower sensitivity to sodium channel blockers and Na+/K+ ATPase inhibitors compared to the hiPSC-CM MEA assay. Calcium channel blockers and a β-adrenergic receptor agonist showed comparable potencies in both models. The in vitro response concentrations from hiPSC-CMs were highly concordant with human effective serum concentrations of potassium and sodium channel blockers. It is concluded that both in vitro models enable the cardiotoxicity screening with different applicability domains. The mESC-CM beating arrest assay may be used as a first step in a tiered approach while the hiPSC-CM MEA assay may be the best starting point for quantitative in vitro to in vivo extrapolations.It is unknown whether the HPV vaccine is effective in immunocompromised women during catch-up ages. We performed a case-control study of 4,357 women with incident CIN2+ (cases) and 51 age-matched, incidence-density selected controls (N = 21,773) enrolled in an integrated health care system from 2006 to 2014. JNJ26481585 Vaccine effectiveness was estimated from multivariable conditional logistic regression models, with results stratified by immunosuppression history, defined as prior HIV infection, solid organ transplant history, or recently prescribed immunosuppressive medications. HPV vaccination resulted in a 19% reduction in CIN2+ rates for women without an immunosuppression history but a nonsignificant 4% reduction for women with an immunosuppression history. Further research is needed to evaluate whether catch-up HPV vaccine effectiveness varies by immunosuppression status, especially given the recent approval of the HPV vaccine for adults up to 45 years of age.