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.

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.

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.

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.

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.

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.

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.

Intraoperative aberrometry versus preoperative biometry for intraocular lens power selection in patients with axial hyperopia.

Purpose: This study was conducted to evaluate the accuracy of intraoperative aberrometry (IA) in intraocular lens (IOL) power calculation and compare it with conventional IOL formulas. Methods: This was a prospective case series. Eyes with visually significant cataract and axial hyperopia (AL <22.0 mm) underwent IA-assisted phacoemulsification with posterior chamber IOL (Alcon AcrySof IQ). Postoperative spherical equivalent (SE) was compared with predicted SE to calculate the outcomes with different formulas (SRK/T, Hoffer Q, Haigis, Holladay 2, Barrett Universal Ⅱ and Hill-RBF). Accuracy of intraoperative aberrometer was compared with other formulas in terms of mean absolute prediction error (MAE), percentage of patients within 0.5 D and 1 D of their target, and percentage of patients going into hyperopic shift. Results: Sixty-five eyes (57 patients) were included. In terms of MAE, both Hoffer Q (MAE = 0.30) and IA (MAE = 0.32) were significantly better than Haigis, SRK/T, and Barrett Universal Ⅱ (P < 0.05). Outcomes within ±0.5 D of the target were maximum with Hoffer Q (80%), superior to IA (Hoffer Q > IA > Holladay 2 > Hill-RBF > Haigis > SRK/T > Barrett Universal Ⅱ). Hoffer Q resulted in minimum hyperopic shift (30.76%) followed by Hill-RBF (38.46%), Holladay 2 (38.46%), Haigis (43.07%), and then IA (46.15%), SRK/T (50.76%) and Barrett Universal Ⅱ (53.84%). Conclusion: IA was more effective (statistically significant) in predicting IOL power than Haigis, SRK/T, and Barrett Universal Ⅱ although it was equivalent to Hoffer Q. Hoffer Q was superior to all formulas in terms of percentage of patients within 0.5 D of their target refractions and percentage of patients going into hyperopic shift.

Evaluating the effect of measles and rubella mass vaccination campaigns on seroprevalence in India: a before-and-after cross-sectional household serosurvey in four districts, 2018-2020.

BACKGROUND: India did phased measles-rubella supplementary immunisation activities (MR-SIAs; ie, mass-immunisation campaigns) targeting children aged 9 months to less than 15 years. We estimated measles-rubella seroprevalence before and after the MR-SIAs to quantify the effect on population immunity and identify remaining immunity gaps. METHODS: Between March 9, 2018 and March 19, 2020 we did community-based, cross-sectional serosurveys in four districts in India before and after MR-SIAs. 30 villages or wards were selected within each district, and one census enumeration block from each was selected as the survey cluster. Households were enumerated and 13 children in the younger age group (9 months to <5 years) and 13 children in the older ager group (5 to <15 years) were randomly selected by use of computer-generated random numbers. Serum samples were tested for IgG antibodies to measles and rubella viruses by enzyme immunoassay. FINDINGS: Specimens were collected from 2570 children before the MR-SIA and from 2619 children afterwards. The weighted MR-SIA coverage ranged from 73·7% to 90·5% in younger children and from 73·6% to 93·6% in older children. Before the MR-SIA, district-level measles seroprevalence was between 80·7% and 88·5% among younger children in all districts, and between 63·4% and 84·5% among older children. After the MR-SIA, measles seroprevalence among younger children increased to more than 90% (range 91·5 to 96·0) in all districts except Kanpur Nagar, in which it remained unchanged 80·4%. Among older children, measles seroprevalence increased to more than 90·0% (range 93·7% to 96·5%) in all districts except Hoshiarpur (88·7%). A significant increase in rubella seroprevalence was observed in all districts in both age groups, with the largest effect in Dibrugarh, where rubella seroprevalence increased from 10·6% to 96·5% among younger children. INTERPRETATION: Measles-rubella seroprevalence increased substantially after the MR-SIAs but the serosurvey also identified remaining gaps in population immunity. FUNDING: The Bill & Melinda Gates Foundation and Indian Council of Medical Research.

The interaction analysis between human serum albumin with chlorpyrifos and its derivatives through sub-atomic docking and molecular dynamics simulation techniques.

Chlorpyrifos (CPF) is an extensively used organophosphate pesticide for crop protection. However, there are concerns about it contaminating the environment and human health, with estimated three lakh deaths annually. The molecular modeling protocol was assisted in redesigning thirteen well-known CPF linkers and inserting them at five selectable CPF (R1-R5) positions of CPF to get 258 CPF derivatives. CPF and its derivatives were optimized using LigPrep and docked to a grid centralized on Trp214 using extra precision glide docking. The Binding free energy of complexes was calculated using molecular mechanics/generalized born surface area (MM-GBSA). CPF and CPFD-225 have glide scores of - 3.08 and - 6.152 kcal/mol, respectively, with human serum albumin and ΔG bind for CPF (- 33.041817 kcal/mol) (- 52.825 kcal/mol) for CPF-D225. The top ten CPF derivatives showed at least ninefold better binding free energy than the CPF proposed for polyclonal antibody production. Subsequently, molecular docking studies revealed that CPF and its derivatives could bind to human serum albumin (HSA). Furthermore, using the Desmond package, a 100-ns molecular dynamics (MD) simulation was performed on the potential binding site. The final systems of CPF-HSA and CPF-222D complexes consist of 76,014 and 76,026 atoms, respectively. The physical stability of both the systems (CPF-HSA and CPF-222D) was analyzed by considering the overall potential energy, RMSF, RMSD, Hydrophobic interactions, and water-mediated patterns, which showed total energy of - 141,610 kcal/mol and - 140,150 kcal/mol, respectively. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03344-7.

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.

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.

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.

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.

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.

Protein-protein interaction and in silico mutagenesis studies on IL17A and its peptide inhibitor.

Protein-protein interactions of Interleukin-17 (IL17) play vital role in the autoimmune and inflammatory diseases, such as rheumatoid arthritis, multiple sclerosis, and psoriasis. Potent therapeutics for these diseases could be developed by blocking or modulating these interactions through biologics, peptide inhibitors and small molecule inhibitors. Unlike biologics, peptide inhibitors are cost effective and can be orally available. Peptide inhibitors do not require a binding groove as that of small molecules either. Therefore, crystal structure of IL17A in complex with a high affinity peptide inhibitor (HAP) (1-IHVTIPADLWDWIN-14) is investigated with an aim to find hot spots that could improve its potency. An in silico mutagenesis strategy was implemented using FoldX PSSM to scan for positions tolerant to amino acid substitution. Three positions T4, A7, and N14 showed improved stability when mutated with 'F/M/Y', 'P' and 'F/M/Y', respectively. A set of 31 mutant peptides are designed through combinations of these tolerant mutations using Build Model application of FoldX. Binding affinity and interactions of 31 peptides are assessed through protein-peptide docking and binding free energy calculations. Two peptides namely, P1 ("1-IHVTIPPDLWDWIY-14") and P2 ("1-IHVMIPPDLWDWIF-14") showed better binding affinity to IL17A dimerization site compared to HAP. Interactions of P1, P2 and HAP are also analyzed through 100 ns molecular dynamics simulations using GROMACS v5.0. The results revealed that the P2 peptide likely to offer better potency compared to HAP and P1. Therefore, the P2 peptide can be synthesized to develop oral therapies for autoimmune and inflammatory diseases with further experimental evaluations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02856-y.

Structural changes, increased hypoxia, and oxidative DNA damage in placenta due to maternal smokeless tobacco use.

BACKGROUND: Smokeless tobacco (SLT) consumption during pregnancy is a well-recognized health risk that causes placental damage including hypoxia and oxidative damage. Although consumption of SLT by women varies from region to region, majority of tea leave pluckers consume SLT for relieving stress and pain. Still, the effects of SLT consumption have not been evaluated in tea garden workers (TGW). While previous studies have attempted to report effects of cigarette smoke using in vitro model, hypoxia-inducible factor (HIF)-1α expression in human placentae from pregnant women exposed to SLT has not been previously studied. This study was aimed to explore the effects of SLT consumption on placental structure, expression of HIF-1α and oxidative DNA damage in sample population of TGW. METHODS: A total of 51 placentae were collected from SLT users and nonusers (n = 30 and 21, respectively) with full-term normal delivery, who were involved in the plucking of tea leaves during pregnancy in tea plantation. Low birth weight (LBW, i.e., weight <2,500 g) and normal birth weight (NBW) groups among both SLT user and nonuser were compared for the stated parameters. Placental tissues were processed for transmission electron microscopy (TEM) study and immunohistochemical analysis for the expression of HIF-1α and 8-hydroxy-2'-deoxyguanosine (8-OHdG). RESULTS: Altered ultrastructural characteristics were observed in the tertiary villi of LBW group among SLT users which included endothelial cells protrusion into capillary lumen, degenerated nuclei, significant thickening of trophoblast basement membrane and vasculo-syncytial membrane, abnormalities of the microvilli, swollen or damaged mitochondria, and dilatation in endoplasmic reticulum cisternae. Furthermore, significant reduction in the perimeter, area, and number of the stromal capillary of the tertiary villi of placenta were found in LBW group as compared with NBW group from the SLT users. Enhanced expression for HIF-1α and oxidative DNA damage (8-OHdG) biomarker was observed in SLT users as compared with nonusers. CONCLUSIONS: Maternal SLT exposure during pregnancy may be associated with villus hypoxia and consequently oxidative DNA damage. It is presumed that deleterious effect of SLT exposure on placenta could result in impairment of placental barrier, and restrict nutrient and oxygen supply from mother to fetus, and thus could be a cause of fetal growth restriction.

Achieving successful capsulorhexis in intumescent white mature cataracts to prevent Argentinian flag sign - A new multifaceted approach to meet the challenge.

Purpose: To present a case series of intumescent white cataract cases managed by a new surgical technique to attain a single stage Continuous Curvilinear Capsulorhexis (CCC). Methods: The series included 60 eyes of 60 patients with white cataract which underwent preoperative anterior chamber depth, lens thickness and ultrasonographic A-scan for intralenticular spikes. A partial size main port (~1.8mm) is created as the first entry into the anterior chamber (AC). A 30-gauge needle of insulin syringe entered through a limbal stab incision is used to decompress the anterior and posterior intralenticular compartments. Following which a standard size, one stage capsulorhexis was performed in a trypan blue stained capsule using microcapsulorhexis forceps entered through the partial sized trapezoidal main port. The main port was secondarily enlarged for phacoemulsification. Results: Based on the intraoperative findings, 43 eyes were categorized as Intumescent type-1 cataracts i.e., with presence of actual liquefied cortex aspirated using 30-gauge needle and 17 eyes as Intumescent type-2 cataracts, i.e., presence of swollen lens without any obvious liquefied cortex. Standard size, circular and centred CCC was achieved in 100% of the cases and no Argentinean flag sign was noted. Surgeon perceived raised intralenticular pressure in 41% of the cases in type-1 subset and 61% cases in type-2 subset (P-0.06). Posterior capsular plaque was observed in 22% of the cases, adherent cortex in 25% and anterior capsular plaque in 5% of the cases. At 6weeks follow up 92% patients had best corrected visual acuity of 20/40 or better. Conclusion: A multi-layered approach can help in attaining successful CCC in cases of white mature cataract with high intralenticular pressure.

Transcriptomic landscaping of core genes and pathways of mild and severe psoriasis vulgaris.

Psoriasis is a common chronic inflammatory skin disease affecting >125 million individuals worldwide. The therapeutic course for the disease is generally designed upon the severity of the disease. In the present study, the gene expression profile GSE78097, was retrieved from the National Centre of Biotechnology (NCBI)­Gene Expression Omnibus (GEO) database to explore the differentially expressed genes (DEGs) in mild and severe psoriasis using the Affy package in R software. The Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways of the DEGs were analysed using clusterProfiler, Bioconductor, version 3.8. In addition, the STRING database was used to develop DEG­encoded proteins and a protein­protein interaction network (PPI). Cytoscape software, version 3.7.1 was utilized to construct a protein interaction association network and analyse the interaction of the candidate DEGs encoding proteins in psoriasis. The top 2 hub genes in Cytohubba plugin parameters were validated using immunohistochemical analysis in psoriasis tissues. A total of 382 and 3,001 dysregulated mild and severe psoriasis DEGs were reported, respectively. The dysregulated mild psoriasis genes were enriched in pathways involving cytokine­cytokine receptor interaction and rheumatoid arthritis, whereas cytokine­cytokine receptor interaction, cell cycle and cell adhesion molecules were the most enriched pathways in severe psoriasis group. PL1N1, TLR4, ADIPOQ, CXCL8, PDK4, CXCL1, CXCL5, LPL, AGT, LEP were hub genes in mild psoriasis, whereas BUB1, CCNB1, CCNA2, CDK1, CDH1, VEGFA, PLK1, CDC42, CCND1 and CXCL8 were reported hub genes in severe psoriasis. Among these, CDC42, for the first time (to the best of our knowledge), has been reported in the psoriasis transcriptome, with its involvement in the adaptive immune pathway. Furthermore, the immunoexpression of CDK1 and CDH1 proteins in psoriasis skin lesions were demonstrated using immunohistochemical analysis. On the whole, the findings of the present integrated bioinformatics and immunohistochemical study, may enhance our understanding of the molecular events occurring in psoriasis, and these candidate genes and pathways together may prove to be therapeutic targets for psoriasis vulgaris.