Comparative study of difference in anatomy & histopathology of placenta & umbilical cord in natural pregnancy vs. IVF pregnancy & it's impact on fetal & maternal outcome.

AIM AND OBJECTIVES: Comparison of naturally conceived pregnancy with IVFET pregnancy for feto-maternal outcome and morphology and histopathology of placenta & umbilical cord. METHODS: 100 pregnant women were divided into 2 subsets of spontaneous pregnancy group (n = 50) and the IVFET pregnancy group (n = 50).The two groups were compared for Maternal age, parity, maternal weight gain, prepregnancy maternal BMI, gestational age, birth weight of baby, placental weight, placenta and umbilical cord cross sections, insertion site of the umbilical cord, and length of the umbilical cord. INCLUSION CRITERIA: Patients registered at ANC OPD/ART centre of our institute and subsequently reporting to maternity ward/ labor room for delivery at our centre. EXCLUSION CRITERIA: The pregnancies conceived after ART outside our institute, multifetal pregnancies. Study duration: 01 year Results: Our study revealed that spontaneous pregnancy group had less antenatal co-morbidities with more number of term vaginal deliveries and less intrapartum and neonatal complications compared to IVFET pregnancy women (p < 0.05). CONCLUSIONS: Assisted reproductive technologies have an impact on placental growth and function in pregnancy. The occurrence of placental abnormalities were the most significant and pertinent finding in the IVF-ET placentas. On histopathological examination maternal vascular malperfusion and concomitant anomalies of the umbilical cord were most noticeable findings.

Estrogen Receptor 1 Gene Polymorphism and its Association with Idiopathic Short Stature in North Indian Population.

Background: In the hypothalamic-pituitary-gonadotrophin (HPG) axis, estrogen plays a key role in the bone maturation regulation and growth plates closure. This study was designed to explore the link between single nucleotide polymorphisms (SNPs) in estrogen receptor 1 (ESR1) gene with idiopathic short stature (ISS) susceptibility in the North Indian population. Methods: Four SNPs of the ESR1 gene (rs543650, rs6557177, rs2234693 and rs9340799) were genotyped by Sanger sequencing in 52 ISS patients and 68 controls. Linkage disequilibrium (LD) and haplotyping were done by SNPstat and SHESISplus softwares. Extent of LD was determined by calculating D' and r2 values in SNPs paired combinations. Results: A significant positive association was found between rs6557177 and rs543650 genotype and ISS susceptibility as compared to controls. The frequencies of the rs6557177 CC genotype (p=0.030; OR=0.13; 95% CI:0.01-1.10) and rs543650 genotype TT (p =0.043; OR=0.29; 95% CI: 0.09-0.92) were observed to be increased in ISS group as compared with the control group. However, no significant correlation was observed between clinical parameters of patients and these SNPs. rs543650 shown strong LD with rs2234693 and rs9340799, similarly rs2234693 and rs9340799. Conclusion: Our study showed that CC genotype at rs6557177 and TT genotype of rs543650 of ESR1 constitutes risk factor for developing ISS in North Indian children. In the future, these findings may lead to a better understanding of the SNPs associated with ISS susceptibility.

Influence of forkhead box protein 3 gene polymorphisms in recurrent pregnancy loss: A meta-analysis.

BACKGROUND: Treg cells play an important role in development of tolerance in maternal immune system against the semi-allogenic embryo. Human forkhead box protein 3 (FOXP3) gene, is the major transcription factor responsible for the regulation of Treg function during pregnancy. Single nucleotide polymorphisms (SNPs) of FOXP3 gene have been reported as a risk factor for Recurrent Pregnancy Loss (RPL), however, results from previous studies are inconsistent. METHODOLOGY: We have collected data from different studies to investigate the overall association of FOXP3 SNPs with risk of RPL. PubMed, Google Scholar, Elsevier, and Cochrane databases were searched to identify eligible studies. Odds Ratio (OR) and 95 % Confidence Interval (CI), calculated via fixed effect or random effect models, were used to evaluate strength of association. This meta-analysis included 11 studies (1383 RPL cases and 1413 controls) of 6 SNPs: rs3761548 A/C, rs2232365 A/G, rs2294021 T/C, 2280883 T/C, rs5902434del/ATT and rs141704699C/T, with ≥2 studies per SNPs and at least 1 significant result. RESULTS: We observed that FOXP3 polymorphism was predominantly present in Asian women with history of RPL. rs2232365 A/G, rs3761548 A/C, rs2294021 T/C, rs2280883 T/C and rs5902434del/ATT polymorphisms were significantly associated with risk of RPL in Indian population. Further, among the most commonly seen polymorphism, rs3761548 A/C was significantly associated with risk of RPL in women from Kazakhstan, China and Gaza, Palestine; rs2232365 A/G in populations of Kazakhstan, Egypt, Iran and Gaza, Palestine. Results of this study indicates that FOXP3 polymorphism is significantly associated with risk of RPL, especially in Asians.

Biallelic novel variants in ZNF469 causing Brittle Cornea Syndrome 1: a detailed report of an Indian patient.

BACKGROUND: Variations in ZNF469 have been associated with Brittle Cornea Syndrome that presents with bluish sclera, loss of vision after trivial trauma, arachnodactyly, and joint laxity. MATERIALS AND METHODS: Detailed medical and family history, physical examination, and molecular analysis. RESULTS: A 21-year-old female presented with bluish discoloration of sclera, diminution of vision following trivial trauma in childhood along with hearing loss and systemic features of arachnodactyly and joint laxity. Clinical diagnosis of brittle cornea syndrome was made which was molecularly proven using next-generation sequencing which identified compound heterozygosity in ZNF469 for pathogenic and likely pathogenic nonsense variants. One variant namely NM_001367624.2:c.5882dup was identified in the exon 3 which was novel and classified as likely pathogenic according to American College of Medical Genetics (ACMG) criteria for variant classification. Another variant NM_001367624.2:c.8992C>T in the exon 2 was classified as pathogenic for Brittle Cornea Syndrome 1. CONCLUSIONS: The report adds to the allelic heterogeneity in ZNF469 causative of Brittle Cornea Syndrome 1 and shall acquaint the physicians about this potentially vision threatening, underdiagnosed, rare syndrome.

Impact of Anti-nuclear Antibody Seropositivity on Clinicopathological Parameters, Treatment Response, and Survival in Lymphoma Patients.

PURPOSE: Lymphoproliferative disorders and autoimmune diseases both are interrelated. The high incidence of lymphoma in autoimmune diseases and frequent antinuclear antibody (ANA) positivity in lymphoma patients have been observed. But the impact of ANA positivity on various clinical parameters and responses to therapy has not been elucidated properly. METHODS: In the present study, 73 treatment-naive lymphoma patients were recruited prospectively and samples were collected at baseline and after completion of therapy for evaluation of ANA. Comparative analysis was performed for various parameters between ANA-positive and ANA-negative groups. RESULTS: The prevalence of ANA at baseline was 27% in lymphoma patients which further increased to 35% after chemotherapy. The ANA-positive group had a significantly higher mean age (58±14.7 vs 47±19.9; p=0.01), early stage (77% vs 38%; p=0.02,) and infrequent B-symptoms (25% vs 52%; p=0.03) as compared to ANA-negative group. No significant difference was observed in the response to therapy and survival (both event-free and overall survival). The most frequent ANA pattern was speckled (50%) at baseline, and homogenous (42%) after the therapy. CONCLUSION: ANA is more frequent in lymphoma and increases further after chemotherapy. Higher mean age, early stage, and infrequent B symptoms were found to be significantly more frequent in ANA-positive lymphoma patients; however, only limited evidence supports its role as a prognostic marker or response to therapy. A wider study with appropriate follow-up data and molecular assay could shed light on the immunobiology of ANA production and its more defined clinical utility in lymphoma.

SHOX Variations in Idiopathic Short Stature in North India and a Review of Cases from Asian Countries

Objective: Short stature homeobox (SHOX) haploinsufficiency underlies idiopathic short stature (ISS) and Leri-Weill dyschondrosteosis. The worldwide prevalence of SHOX variations in ISS varies from 2.5% to 15.0%. The aim of this study was to assess the implication of SHOX variation in ISS in North Indians and compare this with other cases of SHOX variations from Asian population. Methods: SHOX gene analysis was carried out by multiplex ligation-dependent probe amplification followed by Sanger sequencing in 54 patients with variable phenotypes. Comparison with other reports in a meta-analysis comprising the current study and 11 previous studies (n=979) was performed. Results: SHOX analysis resulted in 12.9% positivity (7.4% deletions and 5.5% duplications). SHOX association was seen significantly related to gender, with predominance in females (p=0.047). Short arms and forearms were the only significantly associated trait seen in 51.9% of children. The overall prevalence of SHOX variation was 15.2% in Asians with ISS. No significant difference was found in geographical region-specific analysis. Conclusion: This study summarises findings from the last decade and provides an updated picture of the prevalence of SHOX variations in Asians, emphasizing their potential as therapeutic targets in ISS patients. Further high quality, large investigations including functional validation is warranted to validate this association.

Apoptin NLS2 homodimerization strategy for improved antibacterial activity and bio-stability.

The emergence of antibiotic resistance prompts exploration of viable antimicrobial peptides (AMPs) designs. The present study explores the antimicrobial prospects of Apoptin nuclear localization sequence (NLS2)-derived peptide ANLP (PRPRTAKRRIRL). Further, we examined the utility of the NLS dimerization strategy for improvement in antimicrobial activity and sustained bio-stability of AMPs. Initially, the antimicrobial potential of ANLP using antimicrobial peptide databases was analyzed. Then, ANLP along with its two homodimer variants namely ANLP-K1 and ANLP-K2 were synthesized and evaluated for antimicrobial activity against Escherichia coli and Salmonella. Among three AMPs, ANLP-K2 showed efficient antibacterial activity with 12 µM minimum inhibitory concentration (MIC). Slow degradation of ANLP-K1 (26.48%) and ANLP-K2 (13.21%) compared with linear ANLP (52.33%) at 480 min in serum stability assay indicates improved bio-stability of dimeric peptides. The AMPs presented no cytotoxicity in Vero cells. Dye penetration assays confirmed the membrane interacting nature of AMPs. The zeta potential analysis reveals effective charge neutralization of both lipopolysaccharide (LPS) and bacterial cells by dimeric AMPs. The dimeric AMPs on scanning electron microscopy studies showed multiple pore formations on the bacterial surface. Collectively, proposed Lysine scaffold dimerization of Apoptin NLS2 strategy resulted in enhancing antibacterial activity, bio-stability, and could be effective in neutralizing the off-target effect of LPS. In conclusion, these results suggest that nuclear localization sequence with a modified dimeric approach could represent a rich source of template for designing future antimicrobial peptides.

Effects of high-intensity interval training on aerobic capacity and sports-specific skills in basketball players.

INTRODUCTION: High intensity interval training (HIIT) are widely used to improve the cardiac performance in Basketball players. The current study aims to evaluate the effectiveness of High-Intensity Interval Training on the Aerobic Capacity and sports-specific skills in basketball players. METHODS: 40 male basketball players in the age group 18-25 years were recruited after necessary ethical clearance. Athletes were categorized into two groups of 20 people each: Group 1 control group (age: 21.9 ± 2.4 years, height: 184.6 ± 12.1 cm BMI: 23 ± 3 kg/m2) and Group 2 study group with HIIT (age: 21.4 ± 2.6 years, height: 177.4 ± 6.0 cm BMI: 22.1 ± 2.3 kg/m2). The study group players underwent 5 weeks (10 sessions) of HIIT training. Pre and post intervention evaluation of the Aerobic Capacity (VO2 max) and sports-specific skills were quantified for both the groups. Statistical analysis was performed using one tailed t-test with p < 0.05 for significance. Cohen's D method was used to calculate the effect size and minimum important difference. RESULT: There was a significant increase (p < 0.05) in VO2 max (pre:52.8 ± 2.3 ml/min/kg to post: 54.5 ± 2.4 ml/min/kg) in Group 2 whereas in Group 1 the change was not significant (pre:51.1 ± 2.6 ml/min/kg to post: 51.4 ± 2.9 ml/min/kg). Similarly, there was an increase in agility for Group 2 (pre:11.0 ± 1.0 s to post: 10.1 ± 1.0 s) compared to Group 1. In sports specific skills: Control Dribble, passing skills, Lower body power and shooting skills there was a significant increase in post HIIT training for Group 2, whereas in Group 1 there was no significant difference. DISCUSSION: The HIIT training improved the aerobic capacity (VO2 max) and sports-specific skills in basketball players. CONCLUSION: A 5-week HIIT training improved the aerobic capacity and sports specific skills and may be included as a part of training regime to improve the athletic performance in basketball players.

Exploration of Potential Biomarker Genes and Pathways in Kawasaki Disease: An Integrated in-Silico Approach.

Kawasaki disease (KD) is a common childhood systemic vasculitis with a special predilection for coronary arteries. Even after more than five decades of the initial description of the disease, the etiology of KD remains an enigma. This transcriptome data re-analysis study aimed to elucidate the underlying pathogenesis of KD using a bioinformatic approach to identify differentially expressed genes (DEGs) to delineate common pathways involved in KD. Array datasets from the Gene Expression Omnibus database were extracted and subjected to comparative meta-analysis for the identification of prominent DEGs. Fifteen hub genes with high connectivity were selected from these DEGs (IL1B, ITGAM, TLR2, CXCL8, SPI1, S100A12, MMP9, PRF1, TLR8, TREM1, CD44, UBB, FCER1G, IL7R, and FCGR1A). Of these 15 genes, five genes (CXCL8, FCGR1A, IL1B, TLR2, and TLR8) were found to be involved in neutrophil degranulation. To gain further insight into the molecular mechanism, a protein-protein network was established. Significantly enriched pathways based on the above-mentioned genes were mainly centered on biological regulation and signaling events. In addition, the pathway analysis also indicated that the majority of the DEGs in KD were enriched in systemic lupus erythematosus, suggesting a strong interplay between immunological and genetic factors in the pathogenesis of KD. These findings could significantly aid in identifying therapeutic targets and understanding KD biosignatures to design a biomarker panel for early diagnosis and severity of the disease.

Carrier frequency of Spino-muscular atrophy in individuals of a reproductive age group from North India.

Introduction: Spinal muscular atrophy (SMA) is a neuro-muscular disorder caused by biallelic variations in Survival Motor Neuron 1 gene (SMN1) located on chromosome 5q13.2. It is the most common hereditary cause of neonatal death. Ethnicity specific studies are desirable for estimating the prevalence of carrier status of this disease in a population. Objectives: To estimate the carrier frequency of SMA among individuals of a reproductive age group in a North Indian cohort. Methods: SMA carrier screening was offered to individuals of a reproductive age group (>18 years) visiting a tertiary care center. Multiplex ligation-dependent probe amplification (MLPA) and quantitative real-time polymerase chain reaction (PCR) were the molecular techniques used to detect the carrier status. Results: A total of 198 individuals without a family history of SMA were screened in this study. The carrier frequency of heterozygous deletion of SMN1 gene in our cohort was found to be 1 in 30 (~3/100). Conclusion: The carrier frequency of SMA is high in our country. The data from the study emphasize the need of a population carrier screening program on SMA in India.

A Tailored Heptazine-Based Porous Polymeric Network as a Versatile Heterogeneous (Photo)catalyst.

A heptazine-based microporous polymeric network, HMP-TAPA was synthesised by direct coupling of trichloroheptazine and tris(4-aminophenyl)amine (TAPA). A high surface area of 424 m2 /g was achieved, which is the highest surface area among heptazine-based polymeric networks (HMPs). The tailored electron-donor and -acceptor units in HMP-TAPA give broad visible-light absorption. HMP-TAPA was employed as metal-free photocatalyst for oxidative coupling of amines to imines under visible light irradiation with 98 % selectivity. Furthermore, the surface basicity of HMP-TAPA was used to achieve metal-free heterogeneous base catalysis for Knoevenagel condensation under base-free conditions with >99 % conversion. In addition, HMP-TAPA showed extreme robustness over a wide pH range (1-14). The versatility and flexibility of the current material design is beneficial for understanding its photoactivity and surface basicity so as to design dual active (photo)catalyst materials for specific applications.

X-linked frontometaphyseal dysplasia with severe scoliosis and spinal cord compromise in an Indian boy.

Frontometaphyseal dysplasia (FMD) is a rare genetic disorder with morphological abnormalities of the skeletal and extra skeletal tissues. It belongs to the group of otopalatodigital spectrum disorders. Here we report a 12-year-old boy from India with features of frontometaphyseal dysplasia who had severe scoliosis with neurological complications due to spinal cord compromise. Clinical examination of his mother also revealed mild features of FMD. The manuscript highlights the clinical presentation of the disorder and discusses the clinical heterogeneity of the otopalatodigital spectrum disorders.

Advances in Omics Approaches for Abiotic Stress Tolerance in Tomato.

Tomato, one of the most important crops worldwide, has a high demand in the fresh fruit market and processed food industries. Despite having considerably high productivity, continuous supply as per the market demand is hard to achieve, mostly because of periodic losses occurring due to biotic as well as abiotic stresses. Although tomato is a temperate crop, it is grown in almost all the climatic zones because of widespread demand, which makes it challenge to adapt in diverse conditions. Development of tomato cultivars with enhanced abiotic stress tolerance is one of the most sustainable approaches for its successful production. In this regard, efforts are being made to understand the stress tolerance mechanism, gene discovery, and interaction of genetic and environmental factors. Several omics approaches, tools, and resources have already been developed for tomato growing. Modern sequencing technologies have greatly accelerated genomics and transcriptomics studies in tomato. These advancements facilitate Quantitative trait loci (QTL) mapping, genome-wide association studies (GWAS), and genomic selection (GS). However, limited efforts have been made in other omics branches like proteomics, metabolomics, and ionomics. Extensive cataloging of omics resources made here has highlighted the need for integration of omics approaches for efficient utilization of resources and a better understanding of the molecular mechanism. The information provided here will be helpful to understand the plant responses and the genetic regulatory networks involved in abiotic stress tolerance and efficient utilization of omics resources for tomato crop improvement.

Parameters affecting azoxystrobin and imidacloprid degradation in biobed substrates in the North Indian tropical environment.

This study reports degradation of azoxystrobin (AZOXY) and imidacloprid (IMIDA) in the rice straw (RS)/corn cob (CC) and peat (P)/compost (C)-based biomixtures. The effect of biomixture preconditioning (10 days incubation prior to pesticide application), pesticide concentration and moisture content was evaluated. Results suggested that conditioning of biomixture greatly affected IMIDA degradation where half-life (t1/2) was reduced by 5-9 times. This was attributed to higher microbial biomass carbon content and dehydrogenase activity in the conditioned biomixtures. Pesticide application in the conditioned biomixture did not show any negative impact on soil microbial parameters. Both pesticides degraded at faster rate in the rice straw-based biomixtures than in the corn cob-based biomixtures. Degradation slowed down with increase in initial concentration of pesticides in biomixture and 1.6-3.0 (AZOXY) and 2.4-3.6 (IMIDA) times increase in t1/2 values was observed. The moisture content of biomixture showed positive effect on degradation which increased when moisture content was increased from 60 to 80% water holding capacity. The effect was significant for IMIDA degradation in the corn cob-based biomixtures and AZOXY degradation in the peat biomixtures. The rice straw-based biomixtures were better in degrading AZOXY and IMIDA and can be used in biopurification systems.

Kinetics and isotherm modeling of azoxystrobin and imidacloprid retention in biomixtures.

The paper reports the kinetics and adsorption isotherm modeling for imidacloprid (IMIDA) and azoxystrobin (AZOXY) in rice straw (RS)/corn cob (CC) and peat (P)/compost (C) based biomixtures. The pseudo-first-order (PFO), pseudo-second-order (PSO), Elovich and intraparticle diffusion models were used to describe the kinetics. The adsorption data were subjected to the Langmuir and the Freundlich isotherms. Results (r2Adj values) suggested that the modified Elovich model was the best suited to explain the kinetics of IMIDA sorption while different models explained AZOXY sorption kinetics in different biomixtures (PFO in RS + C and RS + P; PSO in CC + P and Elovich in CC + C). Biomixtures varied in their capacity to adsorb both pesticides and the adsorption coefficient (Kd) values were 116.8-369.24 (AZOXY) and 24.2-293.4 (IMIDA). The Freundlich isotherm better explained the sorption of both pesticides. Comparison analysis of linear and nonlinear method for estimating the Freundlich adsorption constants was made. In general, r2Adj values were higher for the nonlinear fit (AZOXY = 0.938-0.982; IMIDA = 0.91-0.970) than the linear fit (AZOXY = 0.886-0.993; IMIDA = 0.870-0.974) suggesting that the nonlinear Freundlich equation better explained the sorption. The rice straw-based biomixtures performed better in adsorbing both the pesticides and can be used in bio-purification systems.

Utilizing recycled LiFePO4 from batteries in combination with B@C3N4 and CuFe2O4 as sustainable nano-junctions for high performance degradation of atenolol.

In this report recycled LiFePO4 (LFP) from exhaust batteries was utilized to form B@C3N4/LiFePO4/CuFe2O4 (BLC) nano-junction as a visible active photocatalyst. The junction synthesized by two routes: Using as extracted LFP and forming LFP by extracted FePO4 and Li2CO3 via in-situ deposition method. The two ternary junctions BLC and BLC (E) (utilizing as extracted LFP) were utilized for visible and solar powered degradation of beta-blocker drug Atenolol (ATL). Varying the loading of CuFe2O4 (CF) which possesses lowest band gap, BLC (10%), BLC-3 (30%), BLC-5 (50%) and BLC-E (30% CF and as extracted LFP) were produced with BLC-3 exhibiting remarkable activity. The optical band gaps of BLC-3 (2.40 eV) and BLC (E) (2.46 eV) and photocurrent responses reveal high visible absorption and highly diminished recombination. 99.5% and 85.3% of ATL (20 mg L-1) could be degraded by BLC-3 and BLC (E) (0.3 g L-1) respectively in 60 min of exposure to Xe lamp and retaining of high activity in natural sunlight. Band-junction analysis, effect of scavengers and effect on teraphthalic acid and nitroblue tetrazolium reveal O2- and OH radicals as active species and mineralization was confirmed by liquid chromatography-mass spectrometer (LC-MS). Cyto-toxicity studies on human peripheral blood cells and effect on growth of Pseudomonas aeruginosa confirm the complete mineralization. The BLC photocatalyst is a promising multi-functional catalyst utilizing LFP (rarely used as photocatalyst) for treatment of pharmaceutical waste water and other environmental applications.