Ametropia detection using a novel, compact wavefront autorefractor

Introduction: Despite the well-known reproducibility issues of subjective refraction, most studies evaluating autorefractors compared differences between the device and subjective refraction. This work evaluated the performance of a novel handheld Hartmann–Shack-based autorefractor using an alternative protocol, which considered the inherent variability of subjective refraction. Methods: Participants underwent an initial measurement with a desktop autorefractor, two subjective refractions (SR1 and SR2) and a final measurement with the QuickSee Free (QSFree) portable autorefractor. Autorefractor performance was evaluated by comparing the differences between the QSFree and each of the subjective refractions with the difference between the subjective refractions (SR1 vs. SR2) using Bland–Altman analysis and percentage of agreement. Results: A total of 75 subjects (53±14years) were enrolled in the study. The average difference in the absolute spherical equivalent (M) between the QSFree and the SR1 and SR2 was ±0.24 and ±0.02D, respectively, that is, very similar or smaller than the SR1 versus SR2 difference (±0.26D). Average differences in astigmatic components were found to be negligible. The results demonstrate that differences between QSFree and both subjective refractions in J0 and J45 were within ±0.50 D for at least 96% of the measurements. The limits of agreement (LOAs) of the differences between QSFree and SR1, as well as QSFree and SR2, were higher than those observed between SR1 and SR2 for M, J0 and J45. Conclusions: A protocol was designed and validated for the evaluation of a refractive device to account for the variability of subjective refraction. This protocol was used to evaluate a novel portable autorefractor and observed a smaller difference between the device and subjective refractions than the difference between the two subjective refraction measurements in terms of mean bias error, although the standard deviation was higherComunidad de Madrid, Grant/Award Number: IND-15478, IND2019/TIC-17116 and IND2020/TIC-17340; Ministerio de Economía y Competitividad, Grant/Award Number: RYC-2016-21125; National Eye Institute, Grant/ Award Number: R44EY025452; Translational Research Institute for Space Health, Grant/ Award Number: NASA NNX16AO69

Pharmacological Elevation of Cellular Dihydrosphingomyelin Provides a Novel Antiviral Strategy against West Nile Virus Infection

The flavivirus life cycle is strictly dependent on cellular lipid metabolism. Polyphenols like gallic acid and its derivatives are promising lead compounds for new therapeutic agents as they can exert multiple pharmacological activities, including the alteration of lipid metabolism. The evaluation of our collection of polyphenols against West Nile virus (WNV), a representative medically relevant flavivirus, led to the identification of N,N'-(dodecane-1,12-diyl)bis(3,4,5-trihydroxybenzamide) and its 2,3,4-trihydroxybenzamide regioisomer as selective antivirals with low cytotoxicity and high antiviral activity (half-maximal effective concentrations [EC50s] of 2.2 and 0.24 μM, respectively, in Vero cells; EC50s of 2.2 and 1.9 μM, respectively, in SH-SY5Y cells). These polyphenols also inhibited the multiplication of other flaviviruses, namely, Usutu, dengue, and Zika viruses, exhibiting lower antiviral or negligible antiviral activity against other RNA viruses. The mechanism underlying their antiviral activity against WNV involved the alteration of sphingolipid metabolism. These compounds inhibited ceramide desaturase (Des1), promoting the accumulation of dihydrosphingomyelin (dhSM), a minor component of cellular sphingolipids with important roles in membrane properties. The addition of exogenous dhSM or Des1 blockage by using the reference inhibitor GT-11 {N-[(1R,2S)-2-hydroxy-1-hydroxymethyl-2-(2-tridecyl-1-cyclopropenyl)ethyl]octanamide} confirmed the involvement of this pathway in WNV infection. These results unveil the potential of novel antiviral strategies based on the modulation of the cellular levels of dhSM and Des1 activity for the control of flavivirus infection.We thank Theodore C. Pierson (National Institutes of Health, USA) for the subgenomic replicon of WNV. This work was supported by the Spanish Ministry of Science and Innovation AEI/10.13039/501100011033 under grants PID2019-105117RR-C21 (to M.A.M.-A.), PID2019-105117RR-C22 (to M.-J.P.-P.), and PID2020-119195RJ-I00 (to N.J.d.O.) and by the AECSIC under grant PIE-201980E100 (to M.-J.P.-P. and A.S.-F.). This research work was also funded by the European Commission-NextGenerationEU (regulation EU 2020/2094) through CSIC’s Global Health Platform (PTI Salud Global). P.M.-C. was supported by an FPI fellowship (PRE2020-093374) from AEI/10.13039/501100011033. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.Peer reviewe