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Browsing by Author "Anjali Rani"

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    PublicationShort Survey
    A comparative analysis of phytochemicals versus synthetic drugs/nanomedicines in the treatment of uterine fibroid: a systematic review
    (Korean Society of Environmental Risk Assessment and Health Science, 2024) Sonal Upadhyay; Vivek Pandey; Anima Tripathi; Alakh N. Sahu; Anjali Rani; Amita Diwakar; Lavina Chaubey; Rashmi Gupta; Pawan K. Dubey
    Most women experience uterine fibroids (UFs), a common benign gynecological tumor, at some point in their reproductive age. There are several pharmacological treatments available to shrink fibroids and lessen the UF symptoms. These medications cost a lot of money, though, and frequently have serious side effects. Therefore, due to their low cost, comparable and powerful therapeutic efficiency and lower side effects, phytochemical-based medications are gaining popularity in these days. This review's goal is to provide a summary of the knowledge that is currently unavailable regarding the mechanisms of the action of various phytochemical-based medications with anti-uterine fibroid efficacy. The present results showed that dietary phytocompounds (dehydroxyelephantopin, butein, capsaicin, fisetin, kaempferol, resveratrol, silibinin and curcumin) could probably be effective as therapeutic compounds for uterine leiomyoma. These phytochemicals indicated their capability to regulate main fibroid promoting and initiating events for instance, proliferation, inflammation, angiogenesis and fibrosis in various experimental setups through modulating various signaling pathways, such as Smad 2/3, PI3K/AKT/mTOR, ERK 1/2 and β-catenin indicating that they could serve as targets for prevention and/or treatment of UFs. This review provides key molecular insights for the development of phytochemical-based novel personalized therapy for non-surgical management of UFs which may help to avoid hysterectomy. © The Author(s), under exclusive licence to Korean Society of Environmental Risk Assessment and Health Science 2023.
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    PublicationArticle
    A novel GLI3c.750delC truncation mutation in a multiplex Greig cephalopolysyndactyly syndrome family with an unusual phenotypic combination in a patient
    (Elsevier B.V., 2014) Rashmi Patel; Fanish Mani Tripathi; Subodh Kumar Singh; Anjali Rani; Visweswar Bhattacharya; Akhtar Ali
    Greig cephalopolysyndactyly (GCPS) syndrome is an autosomal dominant disorder with high penetrance in majority of cases, characterized by a triad of polysyndactyly, macrocephaly and hypertelorism. GCPS is known to be caused by mutations in the transcription factor GLI3 gene (7p13) which results in functional haploinsufficiency of this gene. The present study reports a large multiplex family having 12 members affected with GCPS in 3 generations and several unaffected members showing autosomal dominant pattern of inheritance with complete penetrance. Interestingly an affected member of the family had unusual features including thumb which is although biphalangeal (confirmed with X-ray) but morphologically looks like finger and a unilateral tiny bony outgrown (externally indistinguishable) on the distal phalanx of the first toe of the left foot. This member also presented with mild ichthyosis. Although it is also possible that one or more of these features are coincidentally present in this member and might not be part of GCPS. Resequencing of the GLI3 gene detected a novel frame-shift mutation c.750delC in heterozygous state transmitting in the family and co-segregating with the disorder suggesting it to be the causal for the GCPS phenotype in the family. In silico analysis suggests that this mutation creates a truncated GLI3 protein resulting in its haploinsufficiency leading to GCPS syndrome. Furthermore, genotype-phenotype correlation is supported by the mutation as it lies in the amino terminal domain of the protein. © 2014.
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    Bioinformatics enrichment analysis of genes and pathways related to maternal type 1 diabetes associated with adverse fetal outcomes
    (Elsevier Inc., 2020) Ravi Bhushan; Anjali Rani; Akhtar Ali; Vinay Kumar Singh; Pawan K. Dubey
    Maternal type 1 diabetes mellitus (T1DM) may affect fetal development by altering the gene expression profile of the umbilical cord. The present study aimed to explore the T1DM-induced gene expression changes in the fetal umbilical cord. The raw gene expression profiles (ID: GSE51546) of umbilical cord tissue obtained from six normal mothers (non-diabetic) and six type 1 diabetic mothers were used to identify the differentially expressed genes. Genes that correspond to official gene symbols were selected for protein-protein interaction (PPI) and sub-network construction (combined score > 0.4). Functional annotation for Gene Ontology (GO) and pathway enrichment analysis were performed for genes involved in networking. A total of 110 differentially expressed genes were identified of which 38 were up-regulated while 72 were down-regulated. Only 37 genes were identified to significantly interact with each other. Hub genes including HSPA4, KCTD6, UBE2G1, FBXL19, and EHMT1 were up-regulated while KBTBD7, TRIM32, and NUP were down-regulated. T1DM had a major effect on the expression of genes involved in cellular death and differentiation, cell signaling and communication, protein modification and regulation of GTPase activity. Total 27 pathways were enriched and genes related to Wnt signaling, VEGF signaling, inflammation mediated by chemokine and cytokine signaling pathways, FGF signaling pathways and GnRH receptor pathways were found significantly affected by T1DM. Our results suggest that the T1DM environment seems to alter umbilical cord gene expression involved in the regulation of pathophysiology of the diabetic mother which in turn may lead to long-term consequences in various tissues in infants. This study provides insight into the molecular mechanism underlying the adverse pregnancy outcomes of maternal T1DM. © 2020 Elsevier Inc.
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    Breastfeeding knowledge and behavior among women visiting a tertiary care center in India: A cross-sectional survey
    (Ubiquity Press, 2019) Priya Sultania; Nisha R. Agrawal; Anjali Rani; Dinesh Dharel; Rachael Charles; Rajesh Dudani
    Background: Breastfeeding is commonly practiced by a majority of mothers in developing countries, though there are widespread misconceptions about optimal breastfeeding traditions. In addition to culturally prominent rituals and social norms, incorrect and inadequate breastfeeding knowledge is major factors for this high-risk behavior. Objectives: To assess knowledge, attitude and practices of breastfeeding among girls and women visiting a tertiary care center in India and to find out the factors, which influence the breastfeeding behaviors. Design/Methods: It is a cross-sectional, questionnaire-based study done among women attending outpatient and inpatient Department of Obstetrics & Gynecology of S.S. Hospital, Banaras Hindu University, India. A face-to-face interview using a pre-designed, self-administered, standardized questionnaire regarding knowledge, attitude, and practices of breastfeeding was conducted. The information was collected and analyzed using SPSS statistical software. Findings: Among 1000 women enrolled in the study, 89% were married, 25% were primiparous, and 52% were multiparous. More than 50% were illiterate, 91% unemployed, and 90% had hospital delivery. Of the total 770 mothers, only 55% received proper antenatal care during pregnancy, of which only 40% were counseled about breastfeeding. Regarding knowledge and attitude about breastfeeding, majority females (71.4%) considered breast milk as best food for a newborn, which was better in younger women <20 years (86%). Regarding breastfeeding behavior, only 45% mothers initiated breastfeeding within one hour of delivery, which was worse in home delivered mothers (25%). Most (82%) mothers fed colostrum to their babies but 27% of mothers gave pre-lacteal feeds. Illiterate mothers (56.3%), mothers with only primary education (70%), and unemployed mothers (53.85%) continued to do exclusive breastfeeding without initiating complementary feeds even after six months. Conclusion(s): Although breastfeeding is practiced by a majority of mothers in a developing country like India, there is a significant gap in knowledge and optimal breastfeeding behaviors. Healthy breastfeeding behavior can be encouraged among mothers by proper counseling by health care workers and organizing educational programs focusing women especially with low education and limited resources. © 2019 The Author(s).
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    Complete Androgen Insensitivity Syndrome due to Mutations in the DNA-Binding Domain of the Human Androgen Receptor Gene
    (S. Karger AG, 2018) Pooja Chauhan; Anjali Rani; Surya K. Singh; Amit K. Rai
    Androgen insensitivity syndrome (AIS) is an X-linked recessive disorder with a 46,XY karyotype caused by alterations in the androgen receptor (AR) gene. We have identified 2 mutations in the AR gene that resulted in complete androgen insensitivity syndrome (CAIS) in 2 unrelated cases. This study includes cytogenetics, hormonal, molecular, and bioinformatics analysis including sequencing of the SRY (sex-determining region Y) and AR genes. Mutational analysis in the first case of primary amenorrhea revealed a novel nucleotide substitution (IVS2-2A>G) in the second intron of the AR gene. The mutation is located in the acceptor splice site (2 nucleotides before exon 3) and caused skipping of exon 3 and formation of an abnormal protein. The second mutation (g. 98762_98764delTCT) was identified in a case of oligoamenorrhea and caused the deletion of 1 amino acid (p.Phe583). Both identified mutations were located in the conserved P-box region of the DNA-binding domain which is responsible for base-specific contacts with the DNA major groove. Furthermore, a hormonal imbalance was also noticed in both cases with high levels of gonadotropins like FSH and LH in both cases. The present study concluded that both identified AR mutations are predicted to either abolish or decrease the binding ability of the AR to androgen response elements of its downstream genes. © 2018 S. Karger AG, Basel. Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
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    Correlation of oxidative damage with pro-inflammatory markers (IL-6, TNF-α) in meningocele
    (Journal of Clinical and Diagnostic Research, 2016) Bedabrata Mukhopadhyay; Roshni Gavel; Ajay N. Gongopadhyay; Pooja Vashistha; Anjali Rani; Surendra Pratap Mishra
    Introduction: Oxidative damage induces alteration in the status of pro-inflammatory markers like IL-6 and TNF-α in meningocele. The study was performed with estimation of the levels of MDA (Malonyldialdehyde), SOD (Superoxide dismutase) taken as oxidative damage markers and IL-6 (interleukin 6) and TNF-α (Tumour necrosis factor alpha) taken as inflammatory markers, in the serum of meningocele patients and age, sex matched normal neonates. Correlation among the different serum levels of MDA, SOD, IL-6 and TNF-α was determined. Materials and Methods: It is a case-control study, comprising of 153 participants: 101 newborns with meningocele and 52 healthy newborns. The study was conducted in the Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, in collaboration with the Department of Paediatric Surgery and Department of Obstetrics and Gynecology, Sir Sunderlal Hospital, Banaras Hindu University, Varanasi. The study was conducted during the period of 2012 to 2014. Serum was extracted from blood collected from both groups i.e. meningocele patient group and healthy neonatal control group. The levels of MDA and SOD were determined by spectrophotometric method. IL-6 was determined by the Human IL-6 High Sensitivity ELISA Kit and TNF-α was determined by the Human TNF-α ELISA KIT. Results: The levels of MDA,TNF-α and IL-6 were found to be much higher and level of SOD was found lower in the patients with meningocele as compared to the normal healthy neonates. Conclusion: Increased MDA (oxidative damage product), IL-6, and TNF-α (inflammatory marker) and low level of SOD shows an increased inflammatory response in Meningocele. Our study shows Negative Correlation between MDA and SOD in case & control groups, while a Positive Correlation between TNF alpha and IL-6 in control & case groups. © 2016, Journal of Clinical and Diagnostic Research. All rights reserved.
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    Deoxyelephantopin, a novel naturally occurring phytochemical impairs growth, induces G2/M arrest, ROS-mediated apoptosis and modulates lncRNA expression against uterine leiomyoma
    (Elsevier Masson s.r.l., 2020) Vivek Pandey; Anima Tripathi; Anjali Rani; Pawan K. Dubey
    Deoxyelephantopin (DOE), a phytochemical, extracted and purified from Elephantopus scaber, has been shown to exhibit antitumor activities. Objective of the present study was to investigate anti-tumor and apoptosis-inducing properties of DOE against uterine leiomyoma (UL) and to explore their molecular mechanisms. Primary cell cultures from fresh UL tissue were established and maintained up to 12 passages. The cells exhibited continuous proliferation with 24 -h doubling time until 12 passages and was then subjected to molecular characterization. The growth inhibitory effect of DOE on UL cells was confirmed by colony formation, cellular senescence, AO/PI and DAPI staining. Fluorescent-activated cell sorting (FACS) assay for apoptosis and cell cycle arrest analysis revealed that DOE significantly (p < 0.05) inhibited the UL cell proliferation via cell cycle arrest at G2/M phase and induced apoptosis via ROS production by lowering mitochondrial membrane potential. Subsequently, the DOE induced ROS was markedly attenuated by co-treatment of N-Acetyl-Cysteine (NAC). Our quantitative RT-PCR and western blot results showed up-regulation of Bax, Caspase-3 and down-regulation of Bcl2, P53, αSMA, COL4A2, VEGF, PCNA, Cyclin B1 and oncogenic lncRNAs (H19, HOTAIR, BANCR and ROR) in DOE treated UL cells which further strengthen our findings. In conclusion, DOE inhibits growth of UL cells via cell cycle arrest at G2/M phase, induces ROS-dependent caspase-3-mediated mitochondrial intrinsic apoptotic pathway and down-regulation of oncogenic lncRNA in UL cells. Our findings suggest that DOE deserves for further systematic investigation in the uterine leiomyoma animal model as a novel apoptosis inducer for potential applications in the prevention or treatment of uterine leiomyoma. © 2020 The Authors
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    Does induction or augmentation of labor increase the risk of postpartum hemorrhage in pregnant women with anemia? A multicenter prospective cohort study in India
    (John Wiley and Sons Ltd, 2024) Tuck Seng Cheng; Farzana Zahir; Carolin Solomi; Ashok Verma; Sereesha Rao; Saswati Sanyal Choudhury; Gitanjali Deka; Pranabika Mahanta; Swapna Kakoty; Robin Medhi; Shakuntala Chhabra; Anjali Rani; Amrit Bora; Indrani Roy; Bina Minz; Omesh Kumar Bharti; Rupanjali Deka; Charles Opondo; David Churchill; Marian Knight; Jennifer J. Kurinczuk; Manisha Nair
    Objective: To investigate whether induction/augmentation of labor in pregnant women with anemia increases the risk of postpartum hemorrhage (PPH) and whether this risk varied by indications for labor induction/augmentation and by anemia severity in pregnancy. Methods: In a prospective cohort study of 9420 pregnant women from 13 hospitals across India, we measured hemoglobin concentrations at recruitment (≥28 weeks of gestation) and blood loss after childbirth during follow-up and collected clinical information about PPH. Clinical obstetric and childbirth information at both visits were extracted from medical records. Anemia severity in the third trimester was categorized using hemoglobin concentrations (no/mild anemia: hemoglobin ≥10 g/dL; moderate: hemoglobin 7 to 9.9 g/dL; severe: hemoglobin <7 g/dL), while PPH was defined based on blood loss volume (vaginal births: ≥500 mL or cesarean sections: ≥1000 mL) and clinical diagnosis. Indications for labor induction/augmentation were classified as clinically indicated and elective as per guidelines. We performed multivariable modified Poisson regression analyses to investigate the associations of anemia severity and indications for labor induction/augmentation, including their interaction, with PPH, adjusted for potential confounders. Results: PPH was associated with anemia but not with indications for labor induction/augmentation. However, there was a significant interaction between the two factors in relation to PPH (P = 0.003). Among pregnant women with severe anemia, a higher risk of PPH was associated with elective (adjusted risk ratio, 3.44 [95% confidence interval, 1.29–9.18]) but not with clinically indicated (adjusted risk ratio, 1.22 [95% confidence interval, 0.42–3.55]) labor induction/augmentation. No associations were observed among pregnant women with no/mild and moderate anemia. Conclusion: The risk of PPH is higher in women who have moderate–severe anemia in late pregnancy. Induction/augmentation of labor is generally safe for women with anemia, but it can increase the risk of PPH in women with severe anemia if performed electively. © 2024 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.
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    Focused Cardiac Ultrasound to Guide the Diagnosis of Heart Failure in Pregnant Women in India
    (Elsevier Inc., 2022) Maryam Alsharqi; Vijay A. Ismavel; Linda Arnold; Saswati S. Choudhury; Carolin Solomi V; Sereesha Rao; Tina Nath; Anjali Rani; Isha Goel; Swapna D. Kakoty; Pranabika Mahanta; Indrani Roy; Rupanjali Deka; Charles Opondo; Colin Baigent; Paul Leeson; Manisha Nair
    Background: Cardiac complications are a leading cause of maternal death. Cardiac imaging with echocardiography is important for prompt diagnosis, but it is not available in many low-resource settings. The aim of this study was to determine whether focused cardiac ultrasound performed by trained obstetricians and interpreted remotely by experts can identify cardiac abnormalities in pregnant women in low-resource settings. Methods: A cross-sectional study was conducted among 301 pregnant and postpartum women recruited from 10 hospitals across three states in India. Twenty-two obstetricians were trained in image acquisition using a portable cardiac ultrasound device following a simplified protocol adapted from focus-assessed transthoracic echocardiography protocol. It included parasternal long-axis, parasternal short-axis, and apical four-chamber views on two-dimensional and color Doppler. Independent image interpretation was performed remotely by two experts, in the United Kingdom and India, using a standard semiquantitative assessment protocol. Interrater agreement between the experts was examined using Cohen's κ. Diagnostic accuracy of the method was examined in a subsample for whom both focused and conventional scans were available. Results: Cardiac abnormalities identified using the focused method included valvular abnormalities (27%), rheumatic heart disease (6.6%), derangements in left ventricular size (4.7%) and function (22%), atrial dilatation (19.5%), and pericardial effusion (30%). There was substantial agreement on the cardiac parameters between the two experts, ranging from 93.6% (κ = 0.84) for left ventricular ejection fraction to 100% (κ = 1) for valvular disease. Image quality was graded as good in 79% of parasternal long-axis, 77% of parasternal short-axis and 64% of apical four-chamber views. The chance-corrected κ coefficients indicated fair to moderate agreement (κ = 0.28-0.51) for the image quality parameters. There was good agreement on diagnosis between the focused method and standard echocardiography (78% agreement), compared in 36 participants. Conclusions: The focused method accurately identified cardiac abnormalities in pregnant women and could be used for screening cardiac problems in obstetric settings. © 2022 American Society of Echocardiography
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    Free radicals and antioxidants status in neonates with congenital malformation
    (Wolters Kluwer Medknow Publications, 2015) Bedabrata Mukhopadhyay; Ajay Narayan Gongopadhyay; Anjali Rani; Roshni Gavel; Surendra Pratap Mishra
    Background: Several studies using animal models have shown that oxidative stress during pregnancy may play an important role in causing birth defects. Congenital anomalies affect an estimated 270,000 newborns who die during the first 28 days of life every year from different birth defects. Hence, at present many research works are going on to reduce the infant mortality from congenital anomaly. [1] Objective: The objective was to measure the oxidant and antioxidant level in the serum of newborn babies with the congenital anomaly and compare these levels with age and sex matched normal neonates. This is to identify any role of oxidative stress in the causation of congenital anomaly. Materials and Methods: This case-control study included 159 participants: 106 newborns with the congenital anomaly and 53 healthy newborns. The markers of oxidative stress like serum malondialdehyde (MDA) level, protein carbonyl (PC) level, and the activity of antioxidants such as Vitamin C, glutathione were measured in both cases (neonates with congenital anomaly) and controls (normal healthy neonates). These parameters were statistically compared. Results: MDA levels and PC levels were significantly higher (P < 0.0001), and Vitamin C and reduced glutathione levels were significantly lower (P < 0.0001), in newborns with congenital malformation than in healthy newborns. Conclusions: Increased lipid peroxidation and protein carbonylation might play an important role in the pathogenesis of congenital anomaly. Impairment of the free radical/antioxidant balance is leading to increased free radical damage in neonates with congenital malformation.
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    Genetic variants related to insulin metabolism are associated with gestational diabetes mellitus
    (Elsevier B.V., 2024) Ravi Bhushan; Shafiul Haque; Rakesh Kumar Gupta; Anjali Rani; Amita Diwakar; Sakshi Agarwal; Anima Tripathi; Pawan K. Dubey
    The current study sought to investigate the associations of common genetic risk variants with gestational diabetes mellitus (GDM) risk in the north Indian population and to evaluate their utility in identifying GDM cases. A case-control study, including 300 pregnant women, was included, and clinical and pathological information was collected. The amplification-refractory mutation system (ARMS) was used for genotyping four single nucleotide polymorphisms (SNPs), namely FTO (rs9939609), PPARG2 (rs1801282), SLC30A8 (rs13266634), and TCF7L2 (rs12255372). The odds ratio and confidence interval were determined for each SNP in different genetic models. Further, attributable risk, population penetrance, and relative risk were also calculated. The risk allele A of FTO (rs9939609) poses a two times higher risk of GDM (p = 0.02, OR = 2.5). The CG and GG genotypes of PPARG2 (rs1801282) have half a lower risk of GDM. In SLC30A8 (rs13266634), the recessive model analysis showed a two times higher risk of having GDM, while the recessive model (TT vs. GG + GT) analysis in TCF7L2 (rs12255372) indicates a lower risk of GDM. Finally, the relative risk, population penetrance, and attributable risk for risk allele in all four variants was higher in GDM mothers. All four polymorphisms were found to be significantly associated with BMI, HbA1c, and insulin. Our study first time confirmed a significant association with GDM for four variants, FTO, PPARG2, SLC30A8, and TCF7L2, in the North Indian population. © 2024 Elsevier B.V.
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    Identification of functional SNPs in PAX3 gene and in silico analysis of damaging SNPs in relation to neural tube defect
    (Reed Elsevier India Pvt. Ltd., 2015) Rashmi; Royana Singh; A.N. Gangopadhyay; Anjali Rani; Mayank Shah
    Introduction: PAX3 gene belongs to the class of transcription factor and has a significant role in neural tube development. There are a number of SNP which are associated with neural tube defect. Hence, we must sort functional SNP for a population study. To fulfill this goal data from dbSNP and literature review can be used. Methods: In this study we analyzed the functional and structural impact of SNPs through computational prediction tool. A total of 8947 SNPs were observed from dbSNP in which SNP associated with neural tube defect having missense mutation is rs2234675. This nsSNP was found to be damaging by sequence homology based tool (Provean) and structural homology based tool (Polyphen). Modeling of wild and mutant protein structure were done using RMSD of wild and mutant protein structure were determined using Swiss PDB viewer and then the protein structure stability was determined using I-mutant 3. Results: The nsSNP present in dbSNP i.e., rs2234675 was identified as deleterious, which lead too decrease in stability of PAX3 protein. Discussion: A change of Thr315Lys, i.e. from polar neutral amino acid to polar basic amino acid showed a change in charge to positive and size of amino acid lead to change in structure. The modeled structure further, showed a decrease in stability. The result obtained from insilico study would open new prospect for association of PAX3 with neural tube defect. © 2015 Anatomical Society of India.
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    Identification of Novel Nucleotide Changes in INHBB Gene by Mutation Screening in Females with Ovarian Dysgenesis: A Case Report
    (Avicenna Research Institute, 2021) Pooja Chauhan; Anjali Rani; Amit Kumar Rai
    Background: Inhibin and activin regulate the follicle stimulating hormone level by their antagonistic actions and thus have been considered as strong candidate genes in the etiology of ovarian dysgenesis. In the present study, two cases of primary amenorrhea with poorly developed secondary sexual characteristics were reported. The purpose of the study was to identify mutations in candidate gene. Case Presentation: In this paper, clinical, genetic, biochemical, and molecular findings in female patients with primary amenorrhea were reported. Whole blood culture and G-banding for karyotyping, sequencing, and in silico analysis were performed following the standard protocol. Both cases were cytogenetically characterized as normal females with 46,XX, chromosome constitution. Hormonal assay revealed high level of follicle stimulating hormone and luteinizing hormone. DNA sequence analysis of inhibin identified two novel heterozygous missense mutations of c.975T>A and c.1156G>A which were translated into p.I310N and p.D386N, respectively. These identified positions were highly conserved across species during evolution. In silico prediction tools, intramolecular hydrogen bonding pattern and hydrophobicity analysis, revealed deleterious effect of p.I310N and neutral effect of p.D386N mutation. Conclusion: Our observation suggested that identified novel mutation in the first case might be the reason for ovarian dysgenesis and provides additional support to the previously reported genotype-phenotype correlations. © 2021 Avicenna Research Institute. All rights reserved.
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    Integration of transcriptomics and metabolomics data revealed role of insulin resistant SNW1 gene in the pathophysiology of gestational diabetes
    (Nature Research, 2025) Ravi Bhushan; Rimjhim Trivedi; Ritu Raj; Anjali Rani; Sangeeta Rai; Anima Tripathi; Shiv Govind Rawat; Ajay Kumar; Dinesh Kumar; Pawan Kumar Dubey
    Gestational Diabetes Mellitus (GDM) is an emerging maternal health problem with increasing incidences. The lack of complete understanding of its pathophysiological mechanisms and novel regulatory biomarkers makes early diagnosis difficult. High-throughput RNA sequencing and computational bioinformatics analyses were conducted to identify novel hub genes, and their regulatory mechanisms were validated through qRT-PCR, western blot, and siRNA-mediated knockdown studies. Intermediate metabolites and circulatory levels of amino acids in the serum of GDM patients and healthy controls were measured. Transcriptomic studies identified SNW1 as the most sensitive and specific biomarker, significantly up-regulated in GDM (fold change = 1.09; p < 0.001). Metabolomic studies indicated significantly elevated gluconeogenesis in GDM, evidenced by decreased levels of alanine and increased levels of pyruvate and glucose compared to controls. siRNA-mediated knockdown of SNW1 in PANC1 cells resulted in significant down-regulation of alanine aminotransferase (ALT/GPT) and insulin receptor substrate (IRS1), while glucose transporters (GLUT2/GLUT4) and insulin (INS) were significantly up-regulated at both mRNA and protein levels. This study identified SNW1 as a novel insulin-resistant gene that induces hyperglycemia by elevating gluconeogenesis and decreasing glucose uptake. SNW1 may be considered a potential therapeutic target with clinical utility for the management of GDM. © The Author(s) 2025.
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    Maternal and fetal factors associated with stillbirth in singleton pregnancies in 13 hospitals across six states in India: A prospective cohort study
    (John Wiley and Sons Ltd, 2024) Yebeen Ysabelle Boo; Amrit K. Bora; Shakuntala Chhabra; Saswati S. Choudhury; Gitanjali Deka; Swapna Kakoty; Pramod Kumar; Pranabika Mahanta; Bina Minz; Anjali Rani; Sereesha Rao; Indrani Roy; Carolin Solomi V.; Ashok Verma; Farzana Zahir; Rupanjali Deka; Jennifer J. Kurinczuk; Manisha Nair
    Objective: This study aimed to investigate the incidence of and risk factors for stillbirth in an Indian population. Methods: We conducted a secondary data analysis of a hospital-based cohort from the Maternal and Perinatal Health Research collaboration, India (MaatHRI), including pregnant women who gave birth between October 2018–September 2023. Data from 9823 singleton pregnancies recruited from 13 hospitals across six Indian states were included. Univariable and multivariable Poisson regression analysis were performed to examine the relationship between stillbirth and potential risk factors. Model prediction was assessed using the area under the receiver-operating characteristic (AUROC) curve. Results: There were 216 stillbirths (48 antepartum and 168 intrapartum) in the study population, representing an overall stillbirth rate of 22.0 per 1000 total births (95% confidence interval [CI]: 19.2–25.1). Modifiable risk factors for stillbirth were: receiving less than four antenatal check-ups (adjusted relative risk [aRR]: 1.75, 95% CI: 1.25–2.47), not taking any iron and folic acid supplementation during pregnancy (aRR: 7.23, 95% CI: 2.12–45.33) and having severe anemia in the third trimester (aRR: 3.37, 95% CI: 1.97–6.11). Having pregnancy/fetal complications such as hypertensive disorders of pregnancy (aRR: 1.59, 95% CI: 1.03–2.36), preterm birth (aRR: 4.41, 95% CI: 3.21–6.08) and birth weight below the 10th percentile for gestational age (aRR: 1.35, 95% CI: 1.02–1.79) were also associated with an increased risk of stillbirth. Identified risk factors explained 78.2% (95% CI: 75.0%–81.4%) of the risk of stillbirth in the population. Conclusion: Addressing potentially modifiable antenatal factors could reduce the risk of stillbirths in India. © 2024 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.
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    Maternal and perinatal Health Research Collaboration, India (MaatHRI): Methodology for establishing a hospital-based research platform in a low and middle income country setting
    (F1000 Research Ltd, 2020) Manisha Nair; Babul Bezbaruah; Amrit Krishna Bora; Krishnaram Bora; Shakuntala Chhabra; Saswati S. Choudhury; Arup Choudhury; Dipika Deka; Gitanjali Deka; Vijay Anand Ismavel; Swapna D. Kakoty; Roshine M. Koshy; Pramod Kumar; Pranabika Mahanta; Robin Medhi; Pranoy Nath; Anjali Rani; Indrani Roy; Usha Sarma; Carolin Solomi V; Ratna Kanta Talukdar; Farzana Zahir; Michael Hill; Nimmi Kansal; Reena Nakra; Colin Baigent; Marian Knight; Jenny J. Kurinczuk
    Background: Maternal and perinatal Health Research collaboration, India (MaatHRI) is a research platform that aims to improve evidence-based pregnancy care and outcomes for mothers and babies in India, a country with the second highest burden of maternal and perinatal deaths. The objective of this paper is to describe the methods used to establish and standardise the platform and the results of the process. Methods: MaatHRI is a hospital-based collaborative research platform. It is adapted from the UK Obstetric Surveillance System (UKOSS) and built on a pilot model (IndOSS-Assam), which has been extensively standardised using the following methods: (i) establishing a network of hospitals; (ii) setting up a secure system for data collection, storage and transfer; (iii) developing a standardised laboratory infrastructure; and (iv) developing and implementing regulatory systems. Results: MaatHRI was established in September 2018. Fourteen hospitals participate across four states in India - Assam, Meghalaya, Uttar Pradesh and Maharashtra. The research team includes 20 nurses, a project manager, 16 obstetricians, two pathologists, a public health specialist, a general physician and a paediatrician. MaatHRI has advanced standardisation of data and laboratory parameters, real-time monitoring of data and participant safety, and secure transfer of data. Four observational epidemiological studies are presently being undertaken through the platform. MaatHRI has enabled bi-directional capacity building. It is overseen by a steering committee and a data safety and monitoring board, a process that is not normally used, but was found to be highly effective in ensuring data safety and equitable partnerships in the context of low and middle income countries (LMICs). Conclusion: MaatHRI is the first prototype of UKOSS and other similar platforms in a LMIC setting. The model is built on existing methods but applies new standardisation processes to develop a collaborative research platform that can be replicated in other LMICs. © 2020 Nair M et al.
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    PublicationArticle
    Maternal and perinatal Health Research Collaboration, India (MaatHRI): methodology for establishing a hospitalbased research platform in a low and middle income country setting [version 3; peer review: 2 approved]
    (F1000 Research Ltd, 2021) Manisha Nair; Babul Bezbaruah; Amrit Krishna Bora; Krishnaram Bora; Shakuntala Chhabra; Saswati S. Choudhury; Arup Choudhury; Dipika Deka; Gitanjali Deka; Vijay Anand Ismavel; Swapna D. Kakoty; Roshine M. Koshy; Pramod Kumar; Pranabika Mahanta; Robin Medhi; Pranoy Nath; Anjali Rani; Indrani Roy; Usha Sarma; Carolin Solomi V; Ratna Kanta Talukdar; Farzana Zahir; Michael Hill; Nimmi Kansal; Reena Nakra; Colin Baigent; Marian Knight; Jenny J. Kurinczuk
    Background: Maternal and perinatal Health Research collaboration, India (MaatHRI) is a research platform that aims to improve evidencebased pregnancy care and outcomes for mothers and babies in India, a country with the second highest burden of maternal and perinatal deaths. The objective of this paper is to describe the methods used to establish and standardise the platform and the results of the process. Methods: MaatHRI is a hospital-based collaborative research platform. It is adapted from the UK Obstetric Surveillance System (UKOSS) and built on a pilot model (IndOSS-Assam), which has been extensively standardised using the following methods: (i) establishing a network of hospitals; (ii) setting up a secure system for data collection, storage and transfer; (iii) developing a standardised laboratory infrastructure; and (iv) developing and implementing regulatory systems. Results: MaatHRI was established in September 2018. Fourteen hospitals participate across four states in India – Assam, Meghalaya, Uttar Pradesh and Maharashtra. The research team includes 20 nurses, a project manager, 16 obstetricians, two pathologists, a public health specialist, a general physician and a paediatrician. MaatHRI has advanced standardisation of data and laboratory parameters, realtime monitoring of data and participant safety, and secure transfer of data. Four observational epidemiological studies are presently beingundertaken through the platform. MaatHRI has enabled bi-directional capacity building. It is overseen by a steering committee and a data safety and monitoring board, a process that is not normally used, but was found to be highly effective in ensuring data safety and equitable partnerships in the context of low and middle income countries (LMICs). Conclusion: MaatHRI is the first prototype of UKOSS and other similar platforms in a LMIC setting. The model is built on existing methods but applies new standardisation processes to develop a collaborative research platform that can be replicated in other LMICs © 2021. Nair M et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
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    Multiplex nested polymerase chain reaction targeting multiple genes for the detection of Neisseria gonorrhoeae and Chlamydia trachomatis in genitourinary specimens
    (Wolters Kluwer Medknow Publications, 2019) Ketan Priyadarshi; Pradyot Prakash; Anjali Rani; Satyendra Kumar Singh
    Objectives: The objective of this study was to design and evaluate a novel multiplex nested polymerase chain reaction (PCR) protocol for simultaneous detection of Neisseria gonorrhoeae and Chlamydia trachomatis in genitourinary specimens obtained from symptomatic patients clinically suspected of sexually transmitted infections (STIs), targeting two different genes each for these pathogens. Materials and Methods: A total of 116 genitourinary specimens were collected from men (n = 12) and women (n = 104). Direct microscopy, culture isolation, and antimicrobial susceptibility testing for N. gonorrhoeae were performed. Multiplex nested PCR was performed on clinical samples using novel designed primers targeting porA pseudogene and opa gene of N. gonorrhoeae and momp gene and cryptic plasmid of C. trachomatis simultaneously. DNA sequence analysis of nested PCR amplicons for each of four gene targets was carried out for the validation of in-house designed primers and PCR protocol. Results: A total of 51.72% (60/116) patients were detected to have either of the two STIs. About 35.35% (41/116) of patients were positive for C. trachomatis and 33.62% (39/116) for N. gonorrhoeae by employing multiplex nested PCR. Coinfection with N. gonorrhoeae and C. trachomatis was detected in 17.24% (20/116) patients. 31.5% endocervical swabs (n = 54), 64.4% speculum-assisted high vaginal swabs (n = 45), and 80% self-collected vaginal swabs (n = 5) were detected positive for either of two STIs. Conclusions: The multiplex nested PCR protocol designed and employed in the present study may be used in the diagnosis and management of both symptomatic as well as asymptomatic cases of N. gonorrhoeae and C. trachomatis, particularly among high-risk groups. © 2019 Indian Journal of Sexually Transmitted Diseases and AIDS.
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    PublicationReview
    Patient blood management in India-Review of current practices and feasibility of applying appropriate standard of care guidelines. A position paper by an interdisciplinary expert group
    (Wolters Kluwer Medknow Publications, 2021) Ajay Gandhi; Klaus Görlinger; Sukesh C. Nair; Poonam M. Kapoor; Anjan Trikha; Yatin Mehta; Anil Handoo; Anil Karlekar; Jyoti Kotwal; Joseph John; Shashikant Apte; Vijay Vohra; Gajendra Gupta; Aseem K. Tiwari; Anjali Rani; Shweta A. Singh
    In a developing country like India, with limited resources and access to healthcare facilities, dealing with massive hemorrhage is a major challenge. This challenge gets compounded by pre-existing anemia, hemostatic disorders, and logistic issues of timely transfer of such patients from peripheral hospitals to centers with adequate resources and management expertise. Despite the awareness amongst healthcare providers regarding management modalities of bleeding patients, no uniform Patient Blood Management (PBM) or perioperative bleeding management protocols have been implemented in India, yet. In light of this, an interdisciplinary expert group came together, comprising of experts working in transfusion medicine, hematology, obstetrics, anesthesiology and intensive care, to review current practices in management of bleeding in Indian healthcare institutions and evaluating the feasibility of implementing uniform PBM guidelines. The specific intent was to perform a gap analysis between the ideal and the current status in terms of practices and resources. The expert group identified interdisciplinary education in PBM and bleeding management, bleeding history, viscoelastic and platelet function testing, and the implementation of validated, setting-specific bleeding management protocols (algorithms) as important tools in PBM and perioperative bleeding management. Here, trauma, major surgery, postpartum hemorrhage, cardiac and liver surgery are the most common clinical settings associated with massive blood loss. Accordingly, PBM should be implemented as a multidisciplinary and practically applicable concept in India in a timely manner in order to optimize the use the precious resource blood and to increase patients' safety. © 2021 Journal of Anaesthesiology Clinical Pharmacology Published by Wolters Kluwer-Medknow.
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    Relationship between anaemia, coagulation parameters during pregnancy and postpartum haemorrhage at childbirth: A prospective cohort study
    (BMJ Publishing Group, 2021) Manisha Nair; Shakuntala Chhabra; Saswati Sanyal Choudhury; DIpika Deka; Gitanjali Deka; Swapna D Kakoty; Pramod Kumar; Pranabika Mahanta; Robin Medhi; Anjali Rani; Seeresha Rao; Indrani Roy; Carolin Solomi V; Ratna Kanta Talukdar; Farzana Zahir; Nimmi Kansal; Anil Arora; Charles Opondo; Jane Armitage; Michael Laffan; Simon Stanworth; Maria Quigley; Colin Baigent; Marian Knight; Jennifer J Kurinczuk
    Objectives To investigate the association between coagulation parameters and severity of anaemia (moderate anaemia: haemoglobin (Hb) 7-9.9 g/dL and severe anaemia: Hb <7 g/dL) during pregnancy and relate these to postpartum haemorrhage (PPH) at childbirth. Design A prospective cohort study of pregnant women recruited in the third trimester and followed-up after childbirth. Setting Ten hospitals across four states in India. Participants 1342 pregnant women. Intervention Not applicable. Methods Hb and coagulation parameters: fibrinogen, D-dimer, D-dimer/fibrinogen ratio, platelets and international normalised ratio (INR) were measured at baseline. Participants were followed-up to measure blood loss within 2 hours after childbirth and PPH was defined based on blood loss and clinical assessment. Associations between coagulation parameters, Hb, anaemia and PPH were examined using multivariable logistic regression models. Outcomes measures Adjusted OR with 95% CI. Results In women with severe anaemia during the third trimester, the D-dimer was 27% higher, mean fibrinogen 117 mg/dL lower, D-dimer/fibrinogen ratio 69% higher and INR 12% higher compared with women with no/mild anaemia. Mean platelets in severe anaemia was 37.8×10 9 /L lower compared with women with moderate anaemia. Similar relationships with smaller effect sizes were identified for women with moderate anaemia compared with women with no/mild anaemia. Low Hb and high INR at third trimester of pregnancy independently increased the odds of PPH at childbirth, but the other coagulation parameters were not found to be significantly associated with PPH. Conclusion Altered blood coagulation profile in pregnant women with severe anaemia could be a risk factor for PPH and requires further evaluation. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.
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