Correction: Universal control of proton concentration using an electrochemically generated acid compatible with miniaturization.

[This corrects the article DOI: 10.1039/D2NA00275B.].

Recommendations for diabetic macular edema management by retina specialists and large language model-based artificial intelligence platforms.

PURPOSE: To study the role of artificial intelligence (AI) in developing diabetic macular edema (DME) management recommendations by creating and comparing responses to clinicians in hypothetical AI-generated case scenarios. The study also examined whether its joint recommendations followed national DME management guidelines. METHODS: The AI hypothetically generated 50 ocular case scenarios from 25 patients using keywords like age, gender, type, duration and control of diabetes, visual acuity, lens status, retinopathy stage, coexisting ocular and systemic co-morbidities, and DME-related retinal imaging findings. For DME and ocular co-morbidity management, we calculated inter-rater agreements (kappa analysis) separately for clinician responses, AI-platforms, and the "majority clinician response" (the maximum number of identical clinician responses) and "majority AI-platform" (the maximum number of identical AI responses). Treatment recommendations for various situations were compared to the Indian national guidelines. RESULTS: For DME management, clinicians (ĸ=0.6), AI platforms (ĸ=0.58), and the 'majority clinician response' and 'majority AI response' (ĸ=0.69) had moderate to substantial inter-rate agreement. The study showed fair to substantial agreement for ocular co-morbidity management between clinicians (ĸ=0.8), AI platforms (ĸ=0.36), and the 'majority clinician response' and 'majority AI response' (ĸ=0.49). Many of the current study's recommendations and national clinical guidelines agreed and disagreed. When treating center-involving DME with very good visual acuity, lattice degeneration, renal disease, anaemia, and a recent history of cardiovascular disease, there were clear disagreements. CONCLUSION: For the first time, this study recommends DME management using large language model-based generative AI. The study's findings could guide in revising the global DME management guidelines.

Identification and Functional Characterization of Two Major Loci Associated with Resistance against Brown Planthoppers (Nilaparvata lugens (Stål)) Derived from Oryza nivara.

The brown planthopper (BPH) is a highly destructive pest of rice, causing significant economic losses in various regions of South and Southeast Asia. Researchers have made promising strides in developing resistance against BPH in rice. Introgression line RPBio4918-230S, derived from Oryza nivara, has shown consistent resistance to BPH at both the seedling and adult stages of rice plants. Segregation analysis has revealed that this resistance is governed by two recessive loci, known as bph39(t) and bph40(t), contributing to 21% and 22% of the phenotypic variance, respectively. We later mapped the genes using a backcross population derived from a cross between Swarna and RPBio4918-230S. We identified specific marker loci, namely RM8213, RM5953, and R4M17, on chromosome 4, flanking the bph39(t) and bph40(t) loci. Furthermore, quantitative expression analysis of candidate genes situated between the RM8213 and R4M17 markers was conducted. It was observed that eight genes exhibited up-regulation in RPBio4918-230S and down-regulation in Swarna after BPH infestation. One gene of particular interest, a serine/threonine-protein kinase receptor (STPKR), showed significant up-regulation in RPBio4918-230S. In-depth sequencing of the susceptible and resistant alleles of STPKR from Swarna and RPBio4918-230S, respectively, revealed numerous single nucleotide polymorphisms (SNPs) and insertion-deletion (InDel) mutations, both in the coding and regulatory regions of the gene. Notably, six of these mutations resulted in amino acid substitutions in the coding region of STPKR (R5K, I38L, S120N, T319A, T320S, and F348S) when compared to Swarna and the reference sequence of Nipponbare. Further validation of these mutations in a set of highly resistant and susceptible backcross inbred lines confirmed the candidacy of the STPKR gene with respect to BPH resistance controlled by bph39(t) and bph40(t). Functional markers specific for STPKR have been developed and validated and can be used for accelerated transfer of the resistant locus to elite rice cultivars.

Molecular and Morphological Characterization of Introgression Lines with Resistance to Bacterial Leaf Blight and Blast in Rice.

The present study evaluates marker assisted forward breeding (MAFB)-derived disease resistant introgression lines (ILs) which do not have the targeted resistance genes for bacterial blight (xa5 + xa13 + Xa21) and blast (Pi2 + Pi9 + Pi54). The ILs were derived in the background of two elite rice cultivars, Krishna Hamsa [Recurrent Parent 1 (RP1)] and WGL 14 (RP2), involving multi-parent inter-crossing. Molecular characterization with gene specific markers for seven reported resistance genes each for bacterial blight (Xa33, Xa38, xa23, Xa4, xa8, Xa27 and Xa41) and blast (Pi1, Pi20, Pi38, Pib, Pitp, Pizt and Pi40) revealed the presence of xa8 and Xa38, in addition to the targeted xa5, xa13 and Xa21 for bacterial blight resistance and Pi1, Pi38, Pi40, Pi20, Pib and Pipt, in addition to the targeted Pi9 and Pi54, for blast resistance in various combinations. A maximum of nine resistance genes xa5 + Xa21 + Pi54 + xa8 + Pipt + Pi38 + Pi1 + Pi20 + Pib was observed in RP1-IL 19030 followed by eight genes xa5 + xa13 + Xa21 + xa8 + Pi9 + Pipt + Pi1 + Pi20 in two RP2-ILs, 19344 and 19347. ANOVA revealed the presence of significant variability for all the yield traits except "days to 50% flowering" (DFF). Box plots depicted the seasonal differences in the phenotypic expression of the yield traits. There was significant positive association of grain yield with days to flowering, tiller number and panicle number. Thousand grain weight is also significantly and positively correlated with grain yield. On the contrary, grain yield showed a significantly negative association with plant height. Multi-parent selective inter-crossing in the present study not only led to the development of high yielding disease resistant ILs but also enhanced recovery of the recurrent parent via selection for essential morphological features. More than 90.0% genetic similarity in the ILs based on SNP-based background selection demonstrated the success of multi-parent selective intercrossing in the development of disease resistant NILs.

Genome-wide association studies in rice germplasm reveal significant genomic regions for root and yield-related traits under aerobic and irrigated conditions.

The development of nutrient-use efficient rice lines is a priority amidst the changing climate and depleting resources viz., water, land, and labor for achieving sustainability in rice cultivation. Along with the traditional transplanted irrigated system of cultivation, the dry direct-seeded aerobic system is gaining ground nationwide. The root-related traits play a crucial role in nutrient acquisition, adaptation and need to be concentrated along with the yield-attributing traits. We phenotyped an association panel of 118 rice lines for seedling vigour index (SVI) traits at 14 and 21 days after sowing (DAS), root-related traits at panicle initiation (PI) stage in polythene bags under controlled aerobic condition, yield and yield-related traits under the irrigated condition at ICAR-IIRR, Hyderabad, Telangana; irrigated and aerobic conditions at ARS, Dhadesugur, Raichur, Karnataka. The panel was genotyped using simple sequence repeats (SSR) markers and genome-wide association studies were conducted for identifying marker-trait associations (MTAs). Significant correlations were recorded for root length, root dry weight with SVI, root volume at the PI stage, number of productive tillers per plant, spikelet fertility, the total number of grains per panicle with grain yield per plant under irrigated conditions, and the total number of grains per panicle with grain yield per plant under aerobic condition. The panel was divided into three sub-groups (K = 3) and correlated with the principal component analysis. The maximum number of MTAs were found on chromosomes 2, 3, and 12 with considerable phenotypic variability. Consistent MTAs were recorded for SVI traits at 14 and 21 DAS (RM25310, RM80, RM22961, RM1385), yield traits under irrigated conditions (RM2584, RM5179, RM410, RM20698, RM14753) across years at ICAR-IIRR, grain yield per plant (RM22961, RM1146) under the aerobic condition, grain yield per plant at irrigated ICAR-IIRR and SVI (RM5501), root traits at PI stage (RM2584, RM80, RM410, RM1146, RM18472). Functionally relevant genes near the MTAs through in-silico expression analysis in root and panicle tissues viz., HBF2 bZIP transcription factor, WD40 repeat-like domain, OsPILS6a auxin efflux carrier, WRKY108, OsSCP42, OsMADS80, nodulin-like domain-containing protein, amino acid transporter using various rice expression databases were identified. The identified MTAs and rice lines having high SVI traits (Langphou, TI-128, Mouli, TI-124, JBB-631-1), high yield under aerobic (Phouren, NPK-43, JBB-684, Ratnamudi, TI-112), irrigated conditions (KR-209, KR-262, Phouren, Keibi-Phou, TI-17), robust root traits like root length (MoirangPhou-Angouba, Wangoo-Phou, JBB-661, Dissi, NPK-45), root volume (Ratnachudi, KJ-221, Mow, Heimang-Phou, PUP-229) can be further employed in breeding programs for the targeted environments aimed at improving seedling vigour, yield-related traits under irrigated condition, aerobic condition as adaptability to water-saving technology.

Outcomes of lensectomy with glued intraocular lens and factors associated with failure in eyes with spherophakia and glaucoma.

Purpose: To evaluate the outcomes of lensectomy with a glued intraocular lens (IOL) in spherophakic eyes with secondary glaucoma and assess factors associated with failure. Methods: We prospectively evaluated outcomes of lensectomy with glued IOL in 19 eyes with spherophakia and secondary glaucoma (intraocular pressure (IOP) ≥22 mm Hg and/or glaucomatous optic disc damage) between 2016 and 2018. The vision, refractive error, IOP, antiglaucoma medications (AGMs), optic disc changes, need for glaucoma surgery, and complications were assessed. Success was defined as complete when IOP was ≥5 and ≤21 mmHg without AGMs; qualified success as similar IOP with up to 3 AGM; the need for >3AGM/additional surgery for IOP control was considered a failure. Results: Preoperatively, the median (interquartile range: IQR) age was 18 (13.5-30) years. IOP was 16 (14-22.5) mmHg on a median of 3 (2,3) AGMs. Median postoperative follow up was 27.7 months (11.9, 39.7). Postsurgery, most patients achieved emmetropia, with significantly decreased refractive error from a median spherical equivalent of -12.5D to + 0.5D, P < 0.0002. The complete success probability was 47% (95% confidence intervals (CIs): 29-76%) at 3 months and was 21% (8 - 50%) at 1 year and 3 years. The qualified success probability was 93% (82-100%) at 1 year, which reduced to 79% (60-100%) in 3 years. None of the eyes had any retinal complications. The higher number of preoperative AGM was found to be a significant risk factor (p < 0.02) for the failure of complete success. Conclusion: One-third of the eyes had IOP control without the need for AGM postlensectomy with glued IOL. Surgery resulted in significant improvement in visual acuity. The higher number of preoperative AGM was associated with poor glaucoma control after glued IOL surgery.

Miniaturized Control of Acidity in Multiplexed Microreactors.

The control of acidity drives the assembly of biopolymers that are essential for a wide range of applications. Its miniaturization can increase the speed and the possibilities of combinatorial throughput for their manipulation, similar to the way that the miniaturization of transistors allows logical operations in microelectronics with a high throughput. Here, we present a device containing multiplexed microreactors, each one enabling independent electrochemical control of acidity in ∼2.5 nL volumes, with a large acidity range from pH 3 to 7 and an accuracy of at least 0.4 pH units. The attained pH within each microreactor (with footprints of ∼0.3 mm2 for each spot) was kept constant for long retention times (∼10 min) and over repeated cycles of >100. The acidity is driven by redox proton exchange reactions, which can be driven at different rates influencing the efficiency of the device in order to achieve more charge exchange (larger acidity range) or better reversibility. The achieved performance in acidity control, miniaturization, and the possibility to multiplex paves the way for the control of combinatorial chemistry through pH- and acidity-controlled reactions.

Incidence of post vitrectomy endophthalmitis in India - A multicentric study by VRSI study Group.

INTRODUCTION: The incidence of post vitrectomy endophthalmitis (PVE) is reported to be between 0.02 and 0.84%. Resterilization of single use instruments is a common practice amidst developing countries to make it more affordable to the patients by reducing the cost of the surgery and also reduce the environmental hazard. The aim of our study is to evaluate the incidence of PVE amidst existing sterilization practices of reused instruments in multiple vitreoretinal centres in India. METHODOLOGY: Centres with an endophthalmitis tracking system were invited to participate in a survey. Twenty-five centres were sent a questionnaire via email. The questionnaire included details about the institution, number of vitrectomies performed in a year, sterilization practices followed pre-operatively, intraoperatively and postoperatively, incidence of endophthalmitis and instrument reuse policies. RESULTS: A total of 29 cases of endophthalmitis were reported out of the 47,612 vitrectomies performed across various centres. The mean incidence of endophthalmitis was 0.06%. There was no difference in the rates of endophthalmitis based on various pre-operative, intraoperative or postoperative prophylactic measures. Nearly 80% of the centres change most of the instruments after every case, while the rest reused. The mean number of times a cutter was being reused until discarded was 4.7. Nearly 76% followed a performance-based protocol, and the remaining 24% had a fixed protocol for the number of times an instrument can be reused before discarding it. CONCLUSION: PVE rates are not significantly different in India despite the multiuse of single use instruments. The purpose of this paper is not to suggest an alternate protocol but to creating one in the future with these results in mind, to rationalise the use of single use instruments, make VR surgery more affordable and also have a positive impact on the carbon footprint of consumables in surgery.

Scheimpflug imaging for evaluation of intraocular lens position in modified flanged scleral fixated intraocular lens.

Background: Scleral fixation of intraocular lens (IOLs) is the most preferred technique for the management of aphakia and the techniques have evolved over the years. These methods have their advantages and disadvantages, however, the major concern being the position of the intraocular lens, its stability and complications. The final IOL position is the major determinant of the final visual acuity, and various imaging modalities have been used to quantify the IOL tilt. Objectives: Use of Scheimpflug imaging to evaluate the IOL tilt in modified flanged scleral-fixated intraocular lens (MFSIOL). Design: Retrospective chart review of 41 consecutive patients who underwent MFIOL. Methods: We conducted a retrospective chart review of 41 consecutive patients who underwent MFIOL. The baseline and final best-corrected visual acuity (BCVA), refractive error, and clinical examination findings were recorded. The vertical and horizontal tilts of the IOLs were calculated using the Scheimpflug image. The IOL tilt (in degrees) in the vertical and horizontal axes was the primary outcome and the BCVA, residual refractive error, intraocular pressure, and surgical complications were secondary outcome measures. Results: The mean baseline BCVA was logMAR 0.49, which improved to logMAR 0.356 (p < .005) after the surgery. The mean IOL tilt in the vertical axis was 3.40° (range of 0.0°-8.5°, interquartile range: 1.21-5.66) and in the horizontal axis was 1.35° (range of 0.60°-4.620°, interquartile range: 0.44-1.86), respectively. There was no correlation between angle of IOL tilt and UCVA (r = 0.089, p = 0.580), BCVA (r = 0.109, p = 0.498), final spherical error (r = 0.081, p = 0.615), cylindrical error (r = 0.207, p = 0.195), axial length (r = 0.105, p = 0.514), and IOL power (r = -0.139, p = 0.388). Conclusion: Modified flanged IOL (MFIOL) is an alternative technique for intrascleral fixation of IOL resulting in good lens stability. The IOL tilt achieved by this technique is minimal and did not influence the final visual outcome or spectacle correction. Scheimpflug imaging is simple and non-invasive method to measure the IOL tilt. Plain Language Summary Scheimpflug imaging for modified flanged scleral fixated lens position: This study on 41 eyes was aimed to analyze the lens tilt using Scheimpflug imaging in cases of modified flanged scleral fixation of intraocular lens (MFSFIOL), which is a novel technique to minimize the complications and simplify the procedure. The intraocular lens (IOL) remained stable with an acceptable range of vertical and horizontal tilt. There was no significant effect of IOL tilt on the final best-corrected visual acuity (BCVA) or spectacle correction. Scheimpflug imaging is an accurate and non-invasive technique for assessment of lens position in the patients with intrascleral fixation of IOL.

Long Term Outcomes in Idiopathic Inflammatory Myositis: An Observational Epidemiologic Study over 15 Years.

Background: We report a longitudinal observational cohort of idiopathic inflammatory myositis (IIM) focusing on the long-term clinical outcome and associated parameters. Methods: IIM patients were classified as per Bohan and Peter criteria. In those with ≥ 24 months of follow-up; the treatment response, functional outcomes, and damage at last follow-up were recorded. Complete clinical response and clinical remission as defined by Oddis et al., was used to define outcomes at last follow-up. Results: The cohort consists of 175 patients, mean age 40.9 (+12.6) years, M:F 1:3.3; and the major subsets were dermatomyositis (44.6%), overlap myositis (25.7%), antisynthetase syndrome (6.3%), polymyositis (14.3%), and juvenile DM/OM (8.6%). Ninety-four patients have followed up for 24 months or more, with the median (IQR) of 65(35,100.7) months. Of them, 74.1% and 11.8% had complete and partial clinical responses respectively at the last follow-up. In our cohort 40.2% were off-steroids and 13.8% were in clinical remission at the last follow-up. Complete clinical response was associated with better functional outcomes and lesser damage as determined by HAQ-DI of 0[OR10.9; 95%CI (3.3,160)], MRS [OR 3.2; 95%CI (1.4,7.3)] and lesser MDI [OR 1.7; 95% CI (1.1,2.7)] respectively as compared to partial response (unadjusted analysis). Baseline parameters and IIM subsets did not significantly influence the functional outcome and damage. The mortality rate in our cohort is 24/175 (13.7%), the disease-specific mortality rate being 9.1%. Large majority of deaths were early, associated with active disease. Conclusion: We report good long-term outcomes in all major myositis subsets. Partial clinical response to treatment is associated with worse functional outcomes and damage accrual. Death occurs early in association with active disease.

Progress and prospects in harnessing wild relatives for genetic enhancement of salt tolerance in rice.

Salt stress is the second most devastating abiotic stress after drought and limits rice production globally. Genetic enhancement of salinity tolerance is a promising and cost-effective approach to achieve yield gains in salt-affected areas. Breeding for salinity tolerance is challenging because of the genetic complexity of the response of rice plants to salt stress, as it is governed by minor genes with low heritability and high G × E interactions. The involvement of numerous physiological and biochemical factors further complicates this complexity. The intensive selection and breeding efforts targeted towards the improvement of yield in the green-revolution era inadvertently resulted in the gradual disappearance of the loci governing salinity tolerance and a significant reduction in genetic variability among cultivars. The limited utilization of genetic resources and narrow genetic base of improved cultivars have resulted in a plateau in response to salinity tolerance in modern cultivars. Wild species are an excellent genetic resource for broadening the genetic base of domesticated rice. Exploiting novel genes of underutilized wild rice relatives to restore salinity tolerance loci eliminated during domestication can result in significant genetic gain in rice cultivars. Wild species of rice, Oryza rufipogon and Oryza nivara, have been harnessed in the development of a few improved rice varieties like Jarava and Chinsura Nona 2. Furthermore, increased access to sequence information and enhanced knowledge about the genomics of salinity tolerance in wild relatives has provided an opportunity for the deployment of wild rice accessions in breeding programs, while overcoming the cross-incompatibility and linkage drag barriers witnessed in wild hybridization. Pre-breeding is another avenue for building material that are ready for utilization in breeding programs. Efforts should be directed towards systematic collection, evaluation, characterization, and deciphering salt tolerance mechanisms in wild rice introgression lines and deploying untapped novel loci to improve salinity tolerance in rice cultivars. This review highlights the potential of wild relatives of Oryza to enhance tolerance to salinity, track the progress of work, and provide a perspective for future research.

Mapping QTLs for yield and photosynthesis-related traits in three consecutive backcross populations of Oryza sativa cultivar Cottondora Sannalu (MTU1010) and Oryza rufipogon.

MAIN CONCLUSION: Identification of trait enhancing QTLs for yield and photosynthesis-related traits in rice using interspecific mapping population and chromosome segment substitution lines derived from a cross between Oryza sativa and Oryza rufipogon. Wild rice contains novel genes which can help in improving rice yield. Common wild rice Oryza rufipogon is a known source for enhanced photosynthesis and yield-related traits. We developed BC2F2:3:4 mapping populations using O. rufipogon IC309814 with high photosynthetic rate as donor, and elite cultivar MTU1010 as recurrent parent. Evaluation of 238 BC2F2 families for 13 yield-related traits and 208 BC2F2 families for seven photosynthesis-related physiological traits resulted in identification of significantly different lines which performed better than MTU1010 for various yield contributing traits. 49 QTLs were identified for 13 yield traits and 7 QTLs for photosynthesis-related traits in BC2F2. In addition, 34 QTLs in BC2F3 and 26 QTLs in BC2F4 were also detected for yield traits.11 common QTLs were identified in three consecutive generations and their trait-increasing alleles were derived from O. rufipogon. Significantly, one major effect common QTL qTGW3.1 for thousand grain weight with average phenotypic variance 8.1% and one novel QTL qBM7.1 for biomass were identified. Photosynthesis-related QTLs qPN9.1, qPN12.1, qPN12.2 qSPAD1.1 and qSPAD6.1 showed additive effect from O. rufipogon. A set of 145 CSSLs were identified in BC2F2 which together represented 87% of O. rufipogon genome. In addition, 87 of the 145 CSSLs were significantly different than MTU1010 for at least one trait. The major effect QTLs can be fine mapped for gene discovery. CSSLs developed in this study are a good source of novel alleles from O. rufipogon in the background of Cottondora Sannalu for rapid improvement of any trait in rice.

Universal control of proton concentration using an electrochemically generated acid compatible with miniaturization.

Controlling locally produced acidity in miniaturized spaces is of high importance to manage simultaneous chemical reactions. Here, we present a platform that hosts miniaturized micro-reactors each one enabling electrochemical control of the acidity in ∼nL volumes. We demonstrated the local control of chemical reactions with the deprotection of strong acid labile groups in a region of 150 µm of diameter of upstanding glass using high proton concentrations (∼10-1 M) and the acidity contrasts between the cell region and the outside. We demonstrated accurate control of the proton concentration in aqueous and organic solvents and the control of chemical reactions in organic electrolytes achieved with a sulfonated tetrafluoroethylene-based membrane, which isolates the acid generating electrodes from the reagents in the solution. The quantitative control of the acidity by faradaic currents was demonstrated by the calibration of carboxyfluorescein adjusted with external titrations and with a tautomer transition occurring at pH 4.2. To the best of our knowledge, this platform shows the best control of acidity in the smallest volume reported so far.

Mapping of QTLs for Yield Traits Using F2:3:4 Populations Derived From Two Alien Introgression Lines Reveals qTGW8.1 as a Consistent QTL for Grain Weight From Oryza nivara.

Wild introgressions play a crucial role in crop improvement by transferring important novel alleles and broadening allelic diversity of cultivated germplasm. In this study, two stable backcross alien introgression lines 166s and 14s derived from Swarn/Oryza nivara IRGC81848 were used as parents to generate populations to map quantitative trait loci (QTLs) for yield-related traits. Field evaluation of yield-related traits in F2, F3, and F4 population was carried out in normal irrigated conditions during the wet season of 2015 and dry seasons of 2016 and 2018, respectively. Plant height, tiller number, productive tiller number, total dry matter, and harvest index showed a highly significant association to single plant yield in F2, F3, and F4. In all, 21, 30, and 17 QTLs were identified in F2, F2:3, and F2:4, respectively, for yield-related traits. QTLs qPH6.1 with 12.54% phenotypic variance (PV) in F2, qPH1.1 with 13.01% PV, qTN6.1 with 10.08% PV in F2:3, and qTGW6.1 with 15.19% PV in F2:4 were identified as major effect QTLs. QTLs qSPY4.1 and qSPY6.1 were detected for grain yield in F2 and F2:3 with PV 8.5 and 6.7%, respectively. The trait enhancing alleles of QTLs qSPY4.1, qSPY6.1, qPH1.1, qTGW6.1, qTGW8.1, qGN4.1, and qTDM5.1 were from O. nivara. QTLs of the yield contributing traits were found clustered in the same chromosomal region. qTGW8.1 was identified in a 2.6 Mb region between RM3480 and RM3452 in all three generations with PV 6.1 to 9.8%. This stable and consistent qTGW8.1 allele from O. nivara can be fine mapped for identification of causal genes. From this population, lines C212, C2124, C2128, and C2143 were identified with significantly higher SPY and C2103, C2116, and C2117 had consistently higher thousand-grain weight values than both the parents and Swarna across the generations and are useful in gene discovery for target traits and further crop improvement.

Multiparent-Derived, Marker-Assisted Introgression Lines of the Elite Indian Rice Cultivar, 'Krishna Hamsa' Show Resistance against Bacterial Blight and Blast and Tolerance to Drought.

Major biotic stresses viz., bacterial blight (BB) and blast and brown plant hopper (BPH) coupled with abiotic stresses like drought stress, significantly affect rice yields. To address this, marker-assisted intercross (IC) breeding involving multiple donors was used to combine three BB resistance genes-xa5, xa13 and Xa21, two blast resistance genes-Pi9 and Pi54, two BPH resistance genes-Bph20 and Bph21, and four drought tolerant quantitative trait loci (QTL)-qDTY1.1, qDTY2.1, qDTY3.1 and qDTY12.1-in the genetic background of the elite Indian rice cultivar 'Krishna Hamsa'. Three cycles of selective intercrossing followed by selfing coupled with foreground selection and phenotyping for the target traits resulted in the development of 196 introgression lines (ILs) with a myriad of gene/QTL combinations. Based on the phenotypic reaction, the ILs were classified into seven phenotypic classes of resistance/tolerance to the following: (1) BB, blast and drought-5 ILs; (2) BB and blast-10 ILs; (3) BB and drought-9 ILs; (4) blast and drought-42 ILs; (5) BB-3 ILs; (6) blast-84 ILs; and (7) drought-43 ILs; none of the ILs were resistant to BPH. Positive phenotypic response (resistance) was observed to both BB and blast in 2 ILs, BB in 9 ILs and blast in 64 ILs despite the absence of corresponding R genes. Inheritance of resistance to BB and/or blast in such ILs could be due to the unknown genes from other parents used in the breeding scheme. Negative phenotypic response (susceptibility) was observed in 67 ILs possessing BB-R genes, 9 ILs with blast-R genes and 9 ILs harboring QTLs for drought tolerance. Complex genic interactions and recombination events due to the involvement of multiple donors explain susceptibility in some of the marker positive ILs. The present investigation successfully demonstrates the possibility of rapid development of multiple stress-tolerant/resistant ILs in the elite cultivar background involving multiple donors through selective intercrossing and stringent phenotyping. The 196 ILs in seven phenotypic classes with myriad of gene/QTL combinations will serve as a useful genetic resource in combining multiple biotic and abiotic stress resistance in future breeding programs.

Coats' disease: trends and long-term treatment outcomes in a tertiary referral centre.

BACKGROUND: The long-term treatment outcomes in Coat's disease - particularly in the era of newer pharmacotherapies such as anti-vascular endothelial growth factor (VEGF) agents and depot steroids - are poorly understood. AIM: To describe the clinical features and treatment outcomes of 148 eyes with Coats' disease assessed in a referral centre over 30 years. MATERIALS AND METHODS: We conducted a retrospective chart review of patients diagnosed with Coats' disease between 1 June 1987 and 31 July 2017. The demographic, clinical and treatment data were collected and long-term functional and anatomical outcomes were analysed based on the treatment either with conventional therapy (cryo/laser) or along with adjuvants like intravitreal steroids or anti-VEGFs. RESULTS: The mean age at presentation was 15.22 years (median 11). Familial exudative vitreoretinopathy was the most common referral diagnosis, 76/148 (51.5%), followed by Coats' disease, 37/148 (25%), and retinoblastoma, 35/148 (23.6%). Stage 3B was most common at presentation (31.8%), followed by 2B (22.3%) and 2A (16.9%). A total of 107 patients were treated either with conventional therapy or in combination with adjuvants. The mean follow-up period was 24.95 months. The visual acuity improved from baseline logMAR 2.17 (Snellen-20/2958) to logMAR 1.88 (Snellen-20/1517) at final follow-up (p = 0.004). The improvement in visual acuity was better when the presenting BCVA was <1 logMAR (Snellen 20/200), p = 0.004. No statistically significant change in BCVA was noted between conventional and adjuvant groups, p = 0.5. However, the final anatomical outcome was good in 78/99 (78.8%) in the conventional group and 45/49 (91.8%) in the adjuvant group, respectively (p = 0.046). CONCLUSION: In this series of patients with Coats' disease over three decades, the use of intravitreal steroids or anti-VEGFs as adjuvants resulted in better anatomical outcomes. A better baseline visual acuity, lower stage of the disease, and older age at presentation were found to be the factors leading to favourable visual outcomes. SUMMARY: In the current series of 148 eyes with Coats' disease, adjuvant treatment with intravitreal steroids or anti-VEGFs resulted in better outcomes as compared with conventional cryotherapy or laser photocoagulation alone. Patients with Coats' disease who had presented with better visual acuity at baseline, lower stage of the disease and older age had better final visual outcomes.

Mapping novel QTLs for yield related traits from a popular rice hybrid KRH-2 derived doubled haploid (DH) population.

A doubled haploid (DH) population consisting of 125 DHLs derived from the popular rice hybrid, KRH-2 (IR58025A/KMR3R) was utilized for Quantitative Trait Loci (QTL) mapping to identify novel genomic regions associated with yield related traits. A genetic map was constructed with 126 polymorphic SSR and EST derived markers, which were distributed across rice genome. QTL analysis using inclusive composite interval mapping (ICIM) method identified a total of 24 major and minor effect QTLs. Among them, twelve major effect QTLs were identified for days to fifty percent flowering (qDFF12-1), total grain yield/plant (qYLD3-1 and qYLD6-1), test (1,000) grain weight (qTGW6-1 and qTGW7-1), panicle weight (qPW9-1), plant height (qPH12-1), flag leaf length (qFLL6-1), flag leaf width (qFLW4-1), panicle length (qPL3-1 and qPL6-1) and biomass (qBM4-1), explaining 29.95-56.75% of the phenotypic variability with LOD scores range of 2.72-16.51. Chromosomal regions with gene clusters were identified on chromosome 3 for total grain yield/plant (qYLD3-1) and panicle length (qPL3-1) and on chromosome 6 for total grain yield/plant (qYLD6-1), flag leaf length (qFLL6-1) and panicle length (qPL6-1). Majority of the QTLs identified were observed to be co-localized with the previously reported QTL regions. Five novel, major effect QTLs associated with panicle weight (qPW9-1), plant height (qPH12-1), flag leaf width (qFLW4-1), panicle length (qPL3-1) and biomass (qBM4-1) and three novel minor effect QTLs for panicle weight (qPW3-1 and qPW8-1) and fertile grains per panicle (qFGP5-1) were identified. These QTLs can be used in breeding programs aimed to yield improvement after their validation in alternative populations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-03045-7.

Treatment outcomes of optic disc pit maculopathy over two decades.

AIM: To study the long-term outcomes of optic disc pit maculopathy. METHODS: Electronic medical records of 154 patients with optic disc pit were reviewed and 50 patients with optic disc pit maculopathy who met the study criteria were included in the study. Demographic profile of patients, along with clinical characteristics, optical coherence tomography (OCT) features and change in best-corrected visual acuity (BCVA) was recorded. Patients were treated either by observation, barrage laser alone or pars plana vitrectomy (PPV) with optional additional surgical procedures. The primary outcome measures were the change in BCVA and resolution of fluid on OCT. RESULTS: The mean age of patients was 29.96 years (3-62 years) with a follow-up of 27.16 months. The mean baseline BCVA in observation, laser and vitrectomy group was log MAR 0.94, 0.76 and 0.87 and final BCVA was log MAR 0.9, 0.67 and 0.46, respectively. There was a statistically significant improvement in the final BCVA and reduction in subretinal fluid with resolution of the schisis cavity in vitrectomy group than in other groups. On regression analysis significant association was found between final BCVA with baseline BCVA (R 2 = 0.815, p = 0.002), use of C3 F8 endotempanode (p = 0.004) ILM peeling (p = 0.012) and use of triamcinolone (TA; p = 0.003). No significant association was found with juxtapapillary endolaser (p = 0.062). CONCLUSIONS: In patients with disc pit maculopathy, PPV lead to better functional and anatomical outcomes as compared to laser or observation alone. Use of surgical adjuvants like ILM peeling, TA and C3F8 tamponade improved the outcomes, unlike juxtapapillary endolaser treatment.

An interplay of microglia and matrix metalloproteinase MMP9 under hypoxic stress regulates the opticin expression in retina.

Inflammation plays a key role in the pathogenesis of retinal vascular diseases. We have shown earlier an increase in the activity of matrix metalloproteinases in the vitreous and tears of preterm born babies with retinopathy of prematurity (ROP) compared to those with no-ROP leading to a shift in the balance of angiogenic (vascular endothelial growth factor [VEGF], matrix metalloproteinase [MMPs], complement component [C3]) and anti-angiogenic (opticin, thrombospondin) in ROP eyes. We now confirmed that tear MMP levels in premature infants perfectly correlates with disease severity. Next, we demonstrated that a reduced opticin levels in ROP vitreous are regulated by MMPs secreted by activated microglia. Upon exposing the human microglia cell line (CHME3) to hypoxia, an increased expression of inflammatory proteins (MMP9, VEGF) was noticed while opticin reduced significantly (p = 0.005). Further, the reduced opticin's expression by microglial cells under hypoxia could be rescued by inhibiting the MMP activity using doxycycline and EDTA. The inhibition of MMP activity altered the expression of other key signaling molecules under hypoxia. Our study clearly explains that increased activity of MMPs under hypoxia regulates the expression of opticin as seen in the vitreous humor of ROP and could serve as a potential target for ROP management.

The giant tear of retinal pigment epithelium following focal laser in central serous chorioretinopathy.

A 35-year-old male smoker presented with reduced vision in OD for the previous two years. He reported a further drop in the vision for the previous two weeks after he underwent focal laser elsewhere. Clinical examination and multimodal imaging confirmed a giant tear of the retinal pigment epithelium (RPE) and a focal leak of CSCR. He was managed with the focal laser to the active leak and lifestyle modification. The ocular condition remained stable. RPE rips in CSCR have been reported to occur spontaneously or with an intervention like exogenous use of steroids, or photodynamic therapy (PDT). This case highlighted the fact that focal laser can precipitate RPE rip in a case of CSCR with tense bullous PED. The physician should keep this fact in mind while counselling the patient before a laser procedure and suspect an RPE rip in a patient with CSCR who presents with an acute onset of vision loss.