Sequence-Specific Fidelity Alterations Associated with West Nile Virus Attenuation in Mosquitoes

High rates of error-prone replication result in the rapid accumulation of genetic diversity of RNA viruses. Recent studies suggest that mutation rates are selected for optimal viral fitness and that modest variations in replicase fidelity may be associated with viral attenuation. Arthropod-borne viruses (arboviruses) are unique in their requirement for host cycling and may necessitate substantial genetic and phenotypic plasticity. In order to more thoroughly investigate the correlates, mechanisms and consequences of arbovirus fidelity, we selected fidelity variants of West Nile virus (WNV; Flaviviridae, Flavivirus) utilizing selection in the presence of a mutagen. We identified two mutations in the WNV RNA-dependent RNA polymerase associated with increased fidelity, V793I and G806R, and a single mutation in the WNV methyltransferase, T248I, associated with decreased fidelity. Both deep-sequencing and in vitro biochemical assays confirmed strain-specific differences in both fidelity and mutational bias. WNV fidelity variants demonstrated host-specific alterations to replicative fitness in vitro, with modest attenuation in mosquito but not vertebrate cell culture. Experimental infections of colonized and field populations of Cx. quinquefaciatus demonstrated that WNV fidelity alterations are associated with a significantly impaired capacity to establish viable infections in mosquitoes. Taken together, these studies (i) demonstrate the importance of allosteric interactions in regulating mutation rates, (ii) establish that mutational spectra can be both sequence and strain-dependent, and (iii) display the profound phenotypic consequences associated with altered replication complex function of flaviviruses

Anti-platelet effects of anti-glaucomatous eye drops: An in vitro study on human platelets

Purpose: Altered platelet aggregability has been implicated in the pathogenesis of glaucoma. This study aims to investigate the anti-platelet potential of intraocular pressure lowering drops, with the possibility of establishing it as an additional mechanism of anti-glaucomatous action. Materials and methods: The anti-aggregating effects of a series of anti-glaucomatous eye drops were determined on human platelets in the platelet aggregation model, using four known aggregating factors (platelet activating factor [PAF], adenosine diphosphate [ADP], thrombin receptor-activating peptide [TRAP], and arachidonic acid [AA]). Results: Almost all of the tested samples inhibited platelet aggregation induced by PAF, ADP, TRAP, and AA, except for Alphagan, which did not demonstrate inhibition of ADP- and TRAP-induced aggregation at a wide range of concentrations. Trusopt, Betoptic, and Azarga eye drops were the most potent inhibitors of all four aggregating factors, while Alphagan was the least potent (P<0.05). Conclusion: This study shows that anti-glaucomatous eye drops possess anti-platelet effects, and this was shown for the first time by experimenting on human platelets. © 2017 Moschos et al

Depression in choroidal melanoma patients treated with proton beam radiotherapy

Aim: To determine depression in patients with choroidal melanoma (CM) treated with proton beam radiotherapy. Patients and Methods: This was a cross-sectional study including 50 patients with CM (50% males, mean age=49.88±6.34 years) and 46 age- and sex-matched healthy controls (52% males, mean age=48.60±8.05 years). Participants completed the Patient Health Questionnaire-9 (PHQ-9) and the Zung Self-Rating Depression Scale (SDS) questionnaires. Results: There was a considerable difference in visual acuity as logarithm of the minimum angle of resolution (logMAR) between the patient and control groups (1.16±0.97 and 0.04±0.05 logMAR, respectively, p<0.0001). Both PHQ-9 and SDS scores differed significantly between the two groups (10.18±4.68 and 8.07±4.90, p=0.04; and 47.94±12.56 and 39.91±8.80, p=0.004, respectively). Scores appeared to be positively correlated with logMAR visual acuity (Spearman rho=0.700, p<0.0001 for PHQ-9; and 0.767, p<0.0001 for SDS), and they were also correlated to each other (Spearman rho=0.759, p<0.0001). Conclusion: Patients with CM having undergone proton beam therapy seem to be more depressed compared to a sample of healthy individuals, and the level of depression is correlated with their visual acuity. © 2018 International Institute of Anticancer Research. All rights reserved

Depression in choroidal melanoma patients treated with proton beam radiotherapy

Aim: To determine depression in patients with choroidal melanoma (CM) treated with proton beam radiotherapy. Patients and Methods: This was a cross-sectional study including 50 patients with CM (50% males, mean age=49.88±6.34 years) and 46 age- and sex-matched healthy controls (52% males, mean age=48.60±8.05 years). Participants completed the Patient Health Questionnaire-9 (PHQ-9) and the Zung Self-Rating Depression Scale (SDS) questionnaires. Results: There was a considerable difference in visual acuity as logarithm of the minimum angle of resolution (logMAR) between the patient and control groups (1.16±0.97 and 0.04±0.05 logMAR, respectively, p&lt;0.0001). Both PHQ-9 and SDS scores differed significantly between the two groups (10.18±4.68 and 8.07±4.90, p=0.04; and 47.94±12.56 and 39.91±8.80, p=0.004, respectively). Scores appeared to be positively correlated with logMAR visual acuity (Spearman rho=0.700, p&lt;0.0001 for PHQ-9; and 0.767, p&lt;0.0001 for SDS), and they were also correlated to each other (Spearman rho=0.759, p&lt;0.0001). Conclusion: Patients with CM having undergone proton beam therapy seem to be more depressed compared to a sample of healthy individuals, and the level of depression is correlated with their visual acuity. © 2018 International Institute of Anticancer Research. All rights reserved