Rapid Assessment of Avoidable Visual Impairment in Two Coastal Districts of Eastern India for Determining Effective Coverage: A Cross-Sectional Study

Purpose: To measure the prevalence and causes of visual impairment (VI) among the 40+ age population in two coastal districts of India and to determine the levels of effective cataract surgical coverage (eCSC) and effective refractive error coverage (eREC) in the study population. Methods: A cross-sectional study was done on 4200 people chosen using cluster sampling in two coastal districts of Odisha, an eastern state in India. A team consisting of trained optometrists and social workers conducted the ocular examination which included unaided, pinhole, and aided visual acuity assessments followed by examination of the anterior segment and lens. Results: Overall, 3745 (89.2%) participants were examined from 60 study clusters, 30 in each district. Among those examined, 1677 (44.8%) were men, 2554 (68.2%) were educated and number? (17.8%) used distance spectacles during the survey. The prevalence of VI adjusted for age and gender was 12.77% (95% CI 11.85–13.69%). Multiple logistic regression showed that older age (OR 3.1; 95% CI 2.0–4.7) and urban residence (OR 1.2; 95% CI 1.0–1.6) were associated with VI. Being educated (OR 0.4; 95% CI 0.3–0.6) and using glasses (OR 0.3; 95% CI 0.5–0.2) were found to provide protection; therefore, resulting in lower instances of VI. Cataract (62.7%) and uncorrected refractive errors (27.1%) were the two main causes of VI. The eCSC was 35.1%, the eREC for distance was 40.0%, and the eREC for near was 35.7%. Conclusion: VI remains a challenge in Odisha, as the prevalence is high and the surgical coverage is poor. Nearly 90% of VI is avoidable indicating that targeted interventions are required to address this problem

(R1504) Second-order Modified Nonstandard Runge-Kutta and Theta Methods for One-dimensional Autonomous Differential Equations

Nonstandard finite difference methods (NSFD) are used in physical sciences to approximate solutions of ordinary differential equations whose analytical solution cannot be computed. Traditional NSFD methods are elementary stable but usually only have first order accuracy. In this paper, we introduce two new classes of numerical methods that are of second order accuracy and elementary stable. The methods are modified versions of the nonstandard two-stage explicit Runge-Kutta methods and the nonstandard one-stage theta methods with a specific form of the nonstandard denominator function. Theoretical analysis of the stability and accuracy of both modified NSFD methods is presented. Numerical simulations that concur with the theoretical findings are also presented, which demonstrate the computational advantages of the proposed new modified nonstandard finite difference methods

A DNA nanomachine that maps spatial and temporal pH changes inside living cells

DNA nanomachines are synthetic assemblies that switch between defined molecular conformations upon stimulation by external triggers. Previously, the performance of DNA devices has been limited to in vitro applications. Here we report the construction of a DNA nanomachine called the I-switch, which is triggered by protons and functions as a pH sensor based on fluorescence resonance energy transfer (FRET) inside living cells. It is an efficient reporter of pH from pH 5.5 to 6.8, with a high dynamic range between pH 5.8 and 7. To demonstrate its ability to function inside living cells we use the I-switch to map spatial and temporal pH changes associated with endosome maturation. The performance of our DNA nanodevices inside living systems illustrates the potential of DNA scaffolds responsive to more complex triggers in sensing, diagnostics and targeted therapies in living systems

The non-adrenergic imidazoline-1 receptor protein nischarin is a key regulator of astrocyte glutamate uptake

Astrocytic GLT-1 is the main glutamate transporter involved in glutamate buffering in the brain, pivotal for glutamate removal at excitatory synapses to terminate neurotransmission and for preventing excitotoxicity. We show here that the surface expression and function of GLT-1 can be rapidly modulated through the interaction of its N-terminus with the nonadrenergic imidazoline-1 receptor protein, Nischarin. The phox domain of Nischarin is critical for interaction and internalization of surface GLT-1. Using live super-resolution imaging, we found that glutamate accelerated Nischarin-GLT-1 internalization into endosomal structures. The surface GLT-1 level increased in Nischarin knockout astrocytes, and this correlated with a significant increase in transporter uptake current. In addition, Nischarin knockout in astrocytes is neuroprotective against glutamate excitotoxicity. These data provide new molecular insights into regulation of GLT-1 surface level and function and suggest new drug targets for the treatment of neurological disorders

MRX protects fork integrity at protein-DNA barriers, and its absence causes checkpoint activation dependent on chromatin context

To address how eukaryotic replication forks respond to fork stalling caused by strong non-covalent protein–DNA barriers, we engineered the controllable Fob-block system in Saccharomyces cerevisiae. This system allows us to strongly induce and control replication fork barriers (RFB) at their natural location within the rDNA. We discover a pivotal role for the MRX (Mre11, Rad50, Xrs2) complex for fork integrity at RFBs, which differs from its acknowledged function in double-strand break processing. Consequently, in the absence of the MRX complex, single-stranded DNA (ssDNA) accumulates at the rDNA. Based on this, we propose a model where the MRX complex specifically protects stalled forks at protein–DNA barriers, and its absence leads to processing resulting in ssDNA. To our surprise, this ssDNA does not trigger a checkpoint response. Intriguingly, however, placing RFBs ectopically on chromosome VI provokes a strong Rad53 checkpoint activation in the absence of Mre11. We demonstrate that proper checkpoint signalling within the rDNA is restored on deletion of SIR2. This suggests the surprising and novel concept that chromatin is an important player in checkpoint signalling