Target-based drug repurposing against Candida albicans-A computational modeling, docking, and molecular dynamic simulations study.

The emergence of multidrug-resistant strains of Candida albicans has become a global threat mostly due to co-infection with immune-compromised patients leading to invasive candidiasis. The life-threatening form of the disease can be managed quickly and effectively by drug repurposing. Thus, the study used in silico approaches to evaluate Food and Drug Administration (FDA) approved drugs against three drug targets-TRR1, TOM40, and YHB1. The tertiary structures of three drug targets were modeled, refined, and evaluated for their structural integrity based on PROCHECK, ERRAT, and PROSA. High-throughput virtual screening of FDA-approved drugs (8815), interaction analysis, and energy profiles had revealed that DB01102 (Arbutamine), DB01611 (Hydroxychloroquine), and DB09319 (Carindacillin) exhibited better binding affinity with TRR1, TOM40, and YHB1, respectively. Notably, the molecular dynamic simulation explored that Gln45, Thr119, and Asp288 of TRR1; Thr107 and Ser121 of TOM40; Arg193, Glu213, and Ser228 of YHB1 are crucial residues for stable drug-target interaction. Additionally, it also prioritized Arbutamine-TRR1 as the best drug-target complex based on MM-PBSA (-52.72 kcal/mol), RMSD (2.43 Å), and radius of gyration (-21.49 Å) analysis. In-depth, PCA results supported the findings of molecular dynamic simulations. Interestingly, the conserved region (>70%) among the TRR1 sequences from pathogenic Candida species indicated the effectiveness of Arbutamine against multiple species of Candida as well. Thus, the study dispenses new insight and enriches the understanding of developing an advanced technique to consider potential antifungals against C. albicans. Nonetheless, a detailed experimental validation is needed to investigate the efficacy of Arbutamin against life-threatening candidiasis.

A systematic review on distribution and antifungal resistance pattern of Candida species in the Indian population.

The emergence of antifungal drug resistance in Candida species has led to increased morbidity and mortality in immunocompromised patients. Understanding species distribution and antifungal drug resistance patterns is an essential step for novel drug development. A systematic review was performed addressing this challenge in India with keywords inclusive of 'Candida', 'Antifungal Drug Resistance', 'Candidemia', 'Candidiasis' and 'India'. A total of 106 studies (January 1978-March 2020) from 20 Indian states were included. Of over 11,429 isolates, Candida albicans was the major species accounting for 37.95% of total isolates followed by C. tropicalis (29.40%), C. glabrata (11.68%) and C. parapsilosis (8.36%). Rates of antifungal resistance were highest in non-albicans Candida (NAC) species - C. haemuloni (47.16%), C. krusei (28.99%), C. lipolytica (28.89%) and C. glabrata (20.69%). Approximately 10.34% isolates of C. albicans were observed to be drug resistant. Candida species were frequently resistant to certain azoles (ketoconazole-22.2%, miconazole-22.1% and fluconazole-21.8%). In conclusion, the present systematic review illustrates the overall distribution and antifungal resistance pattern of Candida species among the Indian population that could be helpful in the future for the formation of treatment recommendations for the region but also elsewhere. LAY SUMMARY: A total of 106 studies were reviewed to define the prevalence, distribution and antifungal resistance pattern of Candida species in India. The presented data could become the point of reference for all reported findings on Candida species in India.

Occupational exposure to pesticides in female tea garden workers and adverse birth outcomes.

Pesticides are globally used to eliminate pests from crops and plants. The increased use of pesticides has posed a serious threat to human health. This study evaluates the effects of pesticide exposure on pregnancy outcomes in tea garden workers (TGW). The acetylcholinesterase (AChE) activity was measured in the maternal blood, placenta, and cord blood of TGW and housewives (HWs). The placental structure and expression of hypoxia-inducible factor (HIF)-1α were also analyzed in TGW and HW groups delivering low birth weight (LBW) and normal birth weight (NBW) babies. A significantly decreased AChE activity was observed in maternal blood and cord blood in TGW as compared with HW in the LBW group. However, it did not change significantly in the NBW group (p < .05). The adjusted regression analysis of birth outcomes (birth weight, head circumference, infant's length, and ponderal index) revealed a significant and positive association with the levels of AChE activity in maternal blood, placenta, and cord blood in TGW (p < .05). The histological analysis showed significantly higher placental syncytial knots, chorangiosis, fibrinoid deposition, necrosis, and stromal fibrosis in the LBW group of TGW. Microinfarction, increased fibrinoid deposition, and atypical villi characteristics, such as mushroom-like structures, were observed during scanning electron microscopy along with increased HIF-1α expression in placental tissues of TGW exposed to pesticides. Results suggest that occupational pesticide exposure during pregnancy may decrease AChE activity and cause in utero pathological changes accompanied by an increased HIF-1α expression, which also contributes to placental insufficiency and fetal growth restriction.

Association of maternal determinants with low birth weight babies in tea garden workers of Assam.

AIM: This study was aimed to evaluate the association of maternal determinants with birth weight (BW) of babies in tea garden workers (TGW) and housewives (HW). METHODS: A total of 175 subjects were recruited from Assam Medical College, Dibrugarh, India. In this cross-sectional study, maternal determinants, BW of babies and placental weight were explored in TGW (n = 102) and HW (n = 73). These factors were assessed and correlated by logistic regression models. RESULTS: A higher incidence of low birth weight (LBW) was found in mothers working in the tea garden (48.04%) as compared to HW (10.96%). Activity of plucking of leaves in tea garden by women had a higher risk for LBW babies (adjusted odd ratio [AOR] 4.33, 95% confidence interval [CI] 1.38-13.57, P = 0.012) and decreased placental weight (AOR 11.42, 95% CI 1.18-126.02, P = 0.036) as compared to HW considered as reference group. Women who worked continuously in the tea garden during 9 months of pregnancy also revealed an elevated risk for LBW (AOR 5.32, 95% CI 1.34-21.09, P = 0.017). CONCLUSION: This study suggests the activity of plucking of tea leaves by women is associated with LBW of babies and decreased placental weight. Particularly, if mothers worked continuously in the tea garden during 9 months of pregnancy, it also increased the risk of delivering LBW babies. This exploratory study provides an important platform for further prospective studies, which could be focused on the potential consequences of maternal occupational exposures during pregnancy on fetal development.

Association of pro- and anti-inflammatory cytokines in preeclampsia.

INTRODUCTION: The pro- and anti-inflammatory cytokines play crucial role in the development and functions of placenta. Any changes in these cytokines may be associated with many pregnancy-related disorders like preeclampsia. Therefore, the present study is aimed to study the expression of pro-inflammatory (TNF-α, IL-6) and anti-inflammatory (IL-4, IL-10) cytokines in placenta and serum of preeclamptic pregnant women. MATERIAL AND METHODS: For this study, a total of 194 cases of preeclamptic and control cases were enrolled in two Groups as per the gestational age that is, Group I (28-36 weeks) and II (37 weeks onwards). The number of samples was 55 in Group I and 139 in Group II. The immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) were conducted on placenta and serum of both preeclamptic and normal samples, respectively. IHC results were revalidated by reverse transcriptase PCR (RT-PCR). RESULTS: Both Groups (I, II) of preeclampsia showed amended levels of pro- and anti-inflammatory cytokines in placental tissues and serum samples. The levels of TNF-α and IL-6 were significantly increased in preeclamptic cases (P = 0.0001, P = 0.0001) while the IL-4 and IL-10 were downregulated (P = 0.0001, P = 0.0001) in comparison to control. In addition, a negative correlation was also observed between the two in preeclampsia (P = 0.0001). CONCLUSION: The balanced ratio of pro- and anti-inflammatory cytokines is essential to regulate the maternal inflammation system throughout pregnancy. Therefore, the gradual cytokine profiling of the pregnant women may be useful for the management of preeclampsia.

TiD: Standalone software for mining putative drug targets from bacterial proteome.

TiD is a standalone application, which relies on basic assumption that a protein must be essential for pathogens survival and non-homologous with host to qualify as putative target. With an input bacterial proteome, TiD removes paralogous proteins, picks essential ones, and excludes proteins homologous with host organisms. The targets illustrate non-homology with at least 40 out of 84 gut microbes, considered safe for human. TiD classifies proposed targets as known, novel and virulent. Users can perform pathway analysis, choke point analysis, interactome analysis, subcellular localization and functional annotations through web servers cross-referenced with the application. Drug targets identified by TiD for Listeria monocytogenes, Bacillus anthracis and Pseudomonas aeruginosa have revealed significant overlaps with previous studies. TiD takes <2h to scan putative targets from a bacterial proteome with ~5000 proteins; hence, we propose it as a useful tool for rational drug design. TiD is available at http://bmicnip.in/TiD/.

dbGAPs: A comprehensive database of genes and genetic markers associated with psoriasis and its subtypes.

Psoriasis is a systemic hyperproliferative inflammatory skin disorder, although rarely fatal but significantly reduces quality of life. Understanding the full genetic component of the disease association may provide insight into biological pathways as well as targets and biomarkers for diagnosis, prognosis and therapy. Studies related to psoriasis associated genes and genetic markers are scattered and not easily amendable to data-mining. To alleviate difficulties, we have developed dbGAPs an integrated knowledgebase representing a gateway to psoriasis associated genomic data. The database contains annotation for 202 manually curated genes associated with psoriasis and its subtypes with cross-references. Functional enrichment of these genes, in context of Gene Ontology and pathways, provide insight into their important role in psoriasis etiology and pathogenesis. The dbGAPs interface is enriched with an interactive search engine for data retrieval along with unique customized tools for Single Nucleotide Polymorphism (SNP)/indel detection and SNP/indel annotations. dbGAPs is accessible at http://www.bmicnip.in/dbgaps/.

Probing binding mechanism of interleukin-6 and olokizumab: in silico design of potential lead antibodies for autoimmune and inflammatory diseases.

Computer-aided antibody engineering has been successful in the design of new biologics for disease diagnosis and therapeutic interventions. Interleukin-6 (IL-6), a well-recognized drug target for various autoimmune and inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, and psoriasis, was investigated in silico to design potential lead antibodies. Here, crystal structure of IL-6 along with monoclonal antibody olokizumab was explored to predict antigen-antibody (Ag - Ab)-interacting residues using DiscoTope, Paratome, and PyMOL. Tyr56, Tyr103 in heavy chain and Gly30, Ile31 in light chain of olokizumab were mutated with residues Ser, Thr, Tyr, Trp, and Phe. A set of 899 mutant macromolecules were designed, and binding affinity of these macromolecules to IL-6 was evaluated through Ag - Ab docking (ZDOCK, ClusPro, and Rosetta server), binding free-energy calculations using Molecular Mechanics/Poisson Boltzman Surface Area (MM/PBSA) method, and interaction energy estimation. In comparison to olokizumab, eight newly designed theoretical antibodies demonstrated better result in all assessments. Therefore, these newly designed macromolecules were proposed as potential lead antibodies to serve as a therapeutics option for IL-6-mediated diseases.

Effect of decentration on the quality of vision in two aspheric posterior chamber intraocular lenses: A contralateral eye study.

PURPOSE: To perform an intraindividual comparison of the quality of vision and the effect of decentration between two aspheric intraocular lenses: aspheric balanced curve (ABC) design Vivinex iSert XY1 (Hoya Surgical Optics, Singapore) and anterior aspheric design Tecnis ZCB00 (Abbott Medical Optics, CA). SETTING: Tertiary Eye Care Centre. DESIGN: Prospective, randomized comparative study using a random number table. METHODS: Thirty patients were randomized to the implantation of Vivinex iSert XY1 in one eye and Tecnis ZCB00 in the contralateral eye. Then, 12 weeks postoperatively, a laser ray-tracing aberrometer was used to evaluate the visual Strehl ratio, higher-order aberrations (HOA), decentration of IOL from the visual axis and geometric axis, angle alpha, and angle kappa. Contrast sensitivity was measured using the functional visual analyzer. RESULTS: The visual internal Strehl ratio was higher ( P < 0.05) at all pupil sizes and the spherical aberrations values were lower ( P < 0.05) at larger pupil sizes (5 mm and 6 mm) in the Vivinex group. The mean decentration from the visual axis in the Vivinex group was significantly more than that in the Tecnis group ( P < 0.01). With an increase in angle alpha, there was a greater decline in the visual Strehl ratio for Tecnis; however, there was a statistically significant decline at 3 mm pupil size for Tecnis ZCB00 ( P = 0.028). The contrast sensitivity was similar for both IOLs. CONCLUSION: In comparison to an anterior aspheric design IOL, the ABC design IOL yielded better quality of vision, neutralized spherical aberrations to a larger extent, and provided a relatively superior quality of vision with decentration.

Correlation of anterior segment optical coherence tomography and ultrasound biomicroscopy in congenital corneal opacity.

PURPOSE: To investigate the correlation between swept-source anterior segment optical coherence tomography (AS-OCT) and ultrasound biomicroscopy (UBM) in congenital corneal opacity (CCO). METHODS: All children with unilateral or bilateral congenital corneal opacities who underwent examination under anesthesia (EUA) and anterior segment optical coherence tomography (AS-OCT) imaging from January 1, 2022, to December 31, 2022, were included. Main outcome measures were corneal and anterior segment evaluation and correlation of UBM and AS-OCT findings. RESULTS: A total of 22 eyes of 15 patients were imaged using both technologies. The age at first EUA ranged from 11 days to 4 years. Different phenotypes were classified based on the clinical examination, UBM, and AS-OCT findings. Fourteen eyes were diagnosed with Peters anomaly, congenital corneal staphyloma was observed in 4 eyes, 2 eyes had coloboma, 1 eye had peripheral sclerocornea, and 1 eye was diagnosed with congenital primary aphakia. AS-OCT and UBM findings were closely correlated in 18 of 22 eyes (82%) but AS-OCT failed to provide detailed information in 4 eyes (18%) where UBM revealed more details. CONCLUSIONS: Although AS-OCT offers valuable preliminary data for initial assessment and counseling, it may not consistently provide precise assessments in all cases. Therefore, UBM should be considered for definitive evaluation.

Post-campaign coverage evaluation of a measles and rubella supplementary immunization activity in five districts in India, 2019-2020.

BACKGROUND: In alignment with the Measles and Rubella (MR) Strategic Elimination plan, India conducted a mass measles and rubella vaccination campaign across the country between 2017 and 2020 to provide a dose of MR containing vaccine to all children aged 9 months to 15 years. We estimated campaign vaccination coverage in five districts in India and assessed campaign awareness and factors associated with vaccination during the campaign to better understand reasons for not receiving the dose. METHODS AND FINDINGS: Community-based cross-sectional serosurveys were conducted in five districts of India among children aged 9 months to 15 years after the vaccination campaign. Campaign coverage was estimated based on home-based immunization record or caregiver recall. Campaign coverage was stratified by child- and household-level risk factors and descriptive analyses were performed to assess reasons for not receiving the campaign dose. Three thousand three hundred and fifty-seven children aged 9 months to 15 years at the time of the campaign were enrolled. Campaign coverage among children aged 9 months to 5 years documented or by recall ranged from 74.2% in Kanpur Nagar District to 90.4% in Dibrugarh District, Assam. Similar coverage was observed for older children. Caregiver awareness of the campaign varied from 88.3% in Hoshiarpur District, Punjab to 97.6% in Dibrugarh District, Assam, although 8% of children whose caregivers were aware of the campaign were not vaccinated during the campaign. Failure to receive the campaign dose was associated with urban settings, low maternal education, and lack of school attendance although the associations varied by district. CONCLUSION: Awareness of the MR vaccination campaign was high; however, campaign coverage varied by district and did not reach the elimination target of 95% coverage in any of the districts studied. Areas with lower coverage among younger children must be prioritized by strengthening the routine immunization programme and implementing strategies to identify and reach under-vaccinated children.

Amalgamation of Toll-Like Receptor and Hypoxic Signaling in Etiology of Preeclampsia.

Inflammation and oxidative stress are involved in the pathogenesis of preeclampsia. Therefore, the aim of this study was to investigate the expression of Toll-like receptor (TLR) (TLR-4, HMGB1, NFκB, IκBα) and hypoxic (HIF-1α, HIF-1ß, PHD, pVHL) pathway proteins in the placenta of preeclamptic pregnant women after 28 weeks of gestational period. A possible association between these 2 pathways was also explored. A total of 194 placental tissues of preeclamptic as well as healthy pregnant women were analyzed by immunohistochemistry. On the basis of gestational age, the samples were divided into 2 groups, I (28-36 wk) and II (36 wk onwards), with 55 and 139 samples in the respective groups. The expression of both TLR (TLR-4, HMGB1, NFκB, IκBα) and hypoxic (HIF-1α, HIF-1ß, PHD, pVHL) pathway proteins were significantly modulated in the placental tissues of preeclampsia as compared with control. The 2 pathways were interlinked in preeclampsia. This study highlights the intercorrelation of both TLR and hypoxic signalling pathways that may be a causative factor for the pathophysiology of preeclampsia.

Cyclooxygenase-2 as a therapeutic target against human breast cancer: A comprehensive review.

Cyclooxygenase-2 (COX-2) is a key aspect of the physiology and pathogenesis of various cancer types. Overexpression of this enzyme is responsible for the elevated prostaglandin production and characteristic feature of breast cancer. Inhibition of COX-2 derived prostanoids facilitates anti-inflammatory, analgesic, and antipyretic effects of non-steroid anti-inflammation drugs. The overexpression of COX-2 is associated with inflammation, pain, and fever. The present study provides the updated relevant literature describing the role of well-characterized isoforms of cyclooxygenase with particular emphasis on COX-2, mechanism of action, the effect of the drug, combinatorial drugs, and microarray-based differential expression analysis and network analysis. We have discussed the currently used combinatorial treatments and their challenges in breast cancer. This article is categorized under: Cancer > Computational Models Cancer > Molecular and Cellular Physiology.

Integrated bioinformatics approach to unwind key genes and pathways involved in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the fifth leading cause of death in India. Until now, the exact pathogenesis concerning CRC signaling pathways is largely unknown; however, the diseased condition is believed to deteriorate with lifestyle, aging, and inherited genetic disorders. Hence, the identification of hub genes and therapeutic targets is of great importance for disease monitoring. OBJECTIVE: Identification of hub genes and targets for identification of candidate hub genes for CRC diagnosis and monitoring. MATERIALS AND METHODS: The present study applied gene expression analysis by integrating two profile datasets (GSE20916 and GSE33113) from NCBI-GEO database to elucidate the potential key candidate genes and pathways in CRC. Differentially expressed genes (DEGs) between CRC (195 CRC tissues) and healthy control (46 normal mucosal tissue) were sorted using GEO2R tool. Further, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed using Cluster Profiler in Rv. 3.6.1. Moreover, protein-protein interactions (PPI), module detection, and hub gene identification were accomplished and visualized through the Search Tool for the Retrieval of Interacting Genes, Molecular Complex Detection (MCODE) plug-in of Cytoscape v3.8.0. Further hub genes were imported into ToppGene webserver for pathway analysis and prognostic expression analysis was conducted using Gene Expression Profiling Interactive Analysis webserver. RESULTS: A total of 2221 DEGs, including 1286 up-regulated and 935down-regulated genes mainly enriched in signaling pathways of NOD-like receptor, FoxO, AMPK signalling and leishmaniasis. Three key modules were detected from PPI network using MCODE. Besides, top 20 high prioritized hub genes were selected. Further, prognostic expression analysis revealed ten of the hub genes, namely IL1B, CD44, Glyceraldehyde-3-phosphate dehydrogenase (GAPDH, MMP9, CREB1, STAT1, vascular endothelial growth factor (VEGFA), CDC5 L, Ataxia-telangiectasia mutated (ATM + and CDH1 to be differently expressed in normal and cancer patients. CONCLUSION: The present study proposed five novel therapeutic targets, i.e., ATM, GAPDH, CREB1, VEGFA, and CDH1 genes that might provide new insights into molecular oncogenesis of CRC.

In silico screening, synthesis, characterization and biological evaluation of novel anticancer agents as potential COX-2 inhibitors.

BACKGROUND: Cyclooxygenase enzyme is frequently overexpressed in various types of cancer and found to play a crucial role in poor prognosis in cancer patients. In current research, we have reported the new COX-2 inhibitors for cancer treatment using computer-aided drug design and experimental validation. METHODS: A total of 12,795 compounds from the different databases were used to screen against the COX-2 enzyme. It perceived three new compounds with better binding affinity to the enzyme. Afterwards, physicochemical properties and in silico bioactivity were assessed for efficacy, safety, and structural features required for binding. The molecules were synthesized and confirmed by spectroscopic techniques. Later on, molecules were evaluated for their anti-cancer activity using MCF-7, MDA-MB-231 and SiHa cancer cell lines. RESULTS: Compound ZINC5921547 and ZINC48442590 (4a, and 4b) reduced the MCF-7, MDA-MB-231, and SiHa cells proliferation potently than parent compounds. The PG-E2 estimation shown, both compounds act through the COX-2 PGE2 axis. Compound 4a and 4b block the cell cycle at G1-S phase and induce cancer cell death. CONCLUSIONS: We concluded that compounds 4a and 4b effectively promotes cancer cell death via COX-2 PGE2 axis, and further in vivo studies can be evaluated for development in both compounds as anticancer agents. The compilation of this information will help us to generate better outcome through robust computational methods. The high-quality experimental results may pave the way for identifying effective drug candidates for cancer treatment.

Exploring the molecular underpinning of psoriasis and its associated comorbidities through network approach: cross talks of genes and pathways.

Patients with psoriasis often complain of several linked disorders including autoimmune and cardiometabolic diseases. Understanding of molecular link between psoriasis and associated comorbidities would be of great interest at the point of patient care management. Integrative unbiased network approach, indicates significant unidirectional gene overlap between psoriasis and its associated comorbid condition including obesity (31 upregulated and 26 downregulated), ischemic stroke (14 upregulated and 2 downregulated), dyslipidaemia (5 upregulated, 5 downregulated), atherosclerosis (8 upregulated and 1 downregulated) and type II diabetes (5 upregulated, 5 downregulated). The analysis revealed substantial gene sharing among the different psoriasis-associated comorbidities. Molecular comorbidity index determining the strength of the interrelation between psoriasis and its comorbidities indicates prevalence of dyslipidaemia followed by type II diabetes among psoriasis patients. The Jaccard coefficient indices revealed psoriasis shared maximum number of biological pathways with dyslipidaemia followed by type 2 diabetes, ischemic stroke, obesity and atherosclerosis. Moreover, pathway annotation highlighted nearly 45 shared pathways amongst psoriasis and its comorbidities and a substantial number of shared pathways was found among multi-morbidities. Overall, the present study established conceivable link between psoriasis and comorbid diseases. The shared genes and overlapped pathways may be explored as a common productive target for psoriasis and its comorbid conditions. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03533-y.

NO-NSAIDs. Part 3: nitric oxide-releasing prodrugs of non-steroidal anti-inflammatory drugs.

In continuation of our efforts to discover novel nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) as potentially "Safe NSAIDs," we report herein the design, synthesis and evaluation of 21 new NO-NSAIDs of commonly used NSAIDs such as aspirin, diclofenac, naproxen, flurbiprofen, ketoprofen, sulindac, ibuprofen and indomethacin. These prodrugs have NO-releasing disulfide linker attached to a parent NSAID via linkages such as an ester (compounds 9-16), a double ester (compounds 17-24), an imide (compounds 25-30) or an amide (compounds 31-33). Among these NO-NSAIDs, the ester-containing NO-aspirin (9), NO-diclofenac (10), NO-naproxen (11), and the imide-containing NO-aspirin (25), NO-flurbiprofen (27) and NO-ketoprofen (28) have shown promising oral absorption, anti-inflammatory activity and NO-releasing property, and also protected rats from NSAID-induced gastric damage. NO-aspirin compound 25, on further co-evaluation with aspirin at equimolar doses, exhibited comparable dose-dependent pharmacokinetics, inhibition of gastric mucosal prostaglandin E(2) (PGE(2)) synthesis and analgesic properties to those of aspirin, but retained its gastric-sparing properties even after doubling its oral dose. These promising NO-NSAIDs could therefore represent a new class of potentially "Safe NSAIDs" for the treatment of arthritic pain and inflammation.

Efficacy of 2% Rebamipide Suspension for Vernal Keratoconjunctivitis: A Clinical Comparison with Topical Immune Modulators Cyclosporine and Tacrolimus.

PURPOSE: To compare the efficacy of 2% rebamipide suspension with topical cyclosporine and tacrolimus for managing vernal keratoconjunctivitis (VKC). METHODS: In this prospective, interventional study, 38 patients with moderate to severe VKC were allocated to receive either 2% rebamipide in one eye and 0.03% tacrolimus ointment in the contralateral eye (n = 19) or 2% rebamipide in one eye and 0.05% cyclosporine in the contralateral eye (n = 19) for 12 weeks. Ten ocular signs and 7 symptoms were graded on a scale of 0-3 each for each eye at every visit. RESULTS: Total sign and symptom scores reduced significantly in all 4 subgroups (all p's <0.05) at 12 weeks. Reduction of mean sign scores between rebamipide and tacrolimus (- 4.67 ± 4.63 and - 2.80 ± 3.18 respectively) and between rebamipide and cyclosporine (-6.00 ± 3.74 and -5.42 ± 3.68 respectively) was comparable. Reduction in symptom scores was also comparable between subgroups. CONCLUSION: Our findings suggest that efficacy of topical rebamipide is comparable to topical cyclosporine and tacrolimus for managing moderate to severe VKC and it merits further evaluation as a novel steroid sparing alternative for this disorder.

Effect of decentration on the quality of vision: comparison between aspheric balance curve design and posterior aspheric design intraocular lenses.

PURPOSE: To study the effect of decentration on the quality of vision in 2 aspheric intraocular lenses (IOLs): aspheric balance curve (ABC) design Vivinex iSert XY1 (Hoya Surgical Opticals, Inc.) and posterior aspheric design AcrySof IQ SN60WF (Alcon Laboratories, Inc.). SETTING: Advanced Eye Centre, PGIMER, Chandigarh, India. DESIGN: Randomized prospective trial using a random number table. METHODS: 85 eyes were randomized to group 1 (Vivinex XY1) and group 2 (AcrySof IQ) with 40 and 45 eyes, respectively. The higher-order aberration (HOA) profile, Strehl ratio, decentration of the IOL from the visual axis (decentration from the visual axis [DVA]) and the geometric axis (decentration from the geometric axis [DGA]), angle α, and κ were recorded on the iTrace aberrometer, and contrast sensitivity was measured using the Functional Acuity Contrast Test at 12 weeks postsurgery. RESULTS: A total of 85 eyes in 60 patients were evaluated in this study. The mean values of the Strehl ratio (P = .48) and the HOAs (P = .12) of both IOLs were comparable. The HOAs gradually increased with increasing DVA for both lenses at 3.0 mm, 4.0 mm, and 5.0 mm pupil sizes. On comparing the HOAs with the DGA, a statistically insignificant positive correlation was observed. The Strehl ratio did not deteriorate with an increasing angle α in the Vivinex XY1 group; however, it worsened in the AcrySof IQ group. Contrast sensitivity was comparable in both the IOLs except at 1.5 cycles per degree under photopic conditions where the AcrySof IQ was better. CONCLUSIONS: Decentration of the lens was best measured with respect to the visual axis. In eyes with a large α, the ABC design induced lesser HOAs and maintained a better Strehl ratio.

A Machine Learning-Based Intrauterine Growth Restriction (IUGR) Prediction Model for Newborns.

Intrauterine growth restriction (IUGR) is a condition in which the fetal weight is below the 10th percentile for its gestational age. Prenatal exposure to metals can cause a decrease in fetal growth during gestation thereby reducing birth weight. Therefore, the aim of the present study was to develop a machine learning model for early prediction of IUGR. A total of 126 IUGR and 88 appropriate-for-gestational-age (AGA) samples were collected from the Gynecology Department, Safdarjung Hospital, New Delhi. The predictive models were developed using the Weka software. The models developed using all the features gave the highest accuracy of 95.5% with support vector machine (SMO) algorithm and 88.5% with multilayer perceptron (MLP) algorithm. Further, models developed after feature selection using 14 important and statistically significant variables also gave the highest accuracy of 98.5% with SMO algorithm and 99% with Naïve Bayes (NB) algorithm. The study concluded SMO_31, SMO_14, MLP_31, and NB_14 to be the better classifiers for IUGR prediction.