IndiGenomes: a comprehensive resource of genetic variants from over 1000 Indian genomes.

With the advent of next-generation sequencing, large-scale initiatives for mining whole genomes and exomes have been employed to better understand global or population-level genetic architecture. India encompasses more than 17% of the world population with extensive genetic diversity, but is under-represented in the global sequencing datasets. This gave us the impetus to perform and analyze the whole genome sequencing of 1029 healthy Indian individuals under the pilot phase of the 'IndiGen' program. We generated a compendium of 55,898,122 single allelic genetic variants from geographically distinct Indian genomes and calculated the allele frequency, allele count, allele number, along with the number of heterozygous or homozygous individuals. In the present study, these variants were systematically annotated using publicly available population databases and can be accessed through a browsable online database named as 'IndiGenomes' http://clingen.igib.res.in/indigen/. The IndiGenomes database will help clinicians and researchers in exploring the genetic component underlying medical conditions. Till date, this is the most comprehensive genetic variant resource for the Indian population and is made freely available for academic utility. The resource has also been accessed extensively by the worldwide community since it's launch.

Botanicals as eco friendly biorational alternatives of synthetic pesticides against Callosobruchus spp. (Coleoptera: Bruchidae)-a review.

The article presents the potential of botanicals in the management of Callosobruchus spp., the primary insect pest causing deterioration to a variety of stored legume grains. Different botanical formulations have been reported time to time showing pronounced insecticidal activity, repellence to pest, oviposition deterrency, adult emergence inhibition, ovicidal, larvicidal, pupaecidal activity and feeding deterrency based on their contact toxicity and fumigation effects. Some of the botanicals have also been practically proved efficacious to protect the stored food commodities from the bruchids during storage conditions. Such botanical formulations have shown their promise in integrated management of the pest as semiochemicals by showing behaviour altering efficacy against the bruchids, thereby, reducing the induced pest resistance problem which is frequently reported with synthetic pesticides. Hence, they may be recommended in food security programmes as eco-friendly and biorational alternatives of synthetic pesticides providing integrated management of the losses of stored food commodities due to infestation of bruchids.

Efficacy of essential oils of Lippia alba (Mill.) N.E. Brown and Callistemon lanceolatus (Sm.) Sweet and their major constituents on mortality, oviposition and feeding behaviour of pulse beetle, Callosobruchus chinensis L.

BACKGROUND: Pulse beetle, Callosobruchus chinensis L., is the most destructive insect pest of pulses under storage in Asia and Africa. Keeping in view the negative impacts of synthetic insecticides and the demands of botanical pesticides, the present investigation explores the repellents, antifeedants, ovicidal, larvicidal and pupaecidal activity of two plant essential oils (EOs) and their major components, geranial and 1,8-cineole, when applied as fumigants for the management of the pulse beetle. RESULTS: EO of Callistemon lanceolatus (Sm.) Sweet caused 100% repellency of pulse beetle in a Y-shaped olfactometer at a dose of 150 µL, while Lippia alba (Mill.) N.E. Brown EO and 1,8-cineole showed 76 and 74.7% repellency at the same dose. At 0.1 µL mL(-1) , both the oils and 1,8-cineole provided 100% insect mortality. The EO of C. lanceolatus was recorded as the most effective fumigant, showing 96.03% oviposition deterrency and 100% antifeedant activity at 0.1 µL mL(-1) . The LD(50) of L. alba (11049.2 µL kg(-1) ) and C. lanceolatus (14 626.3 µL kg(-1) ) exhibited their favourable safety profiles when recorded on mice. CONCLUSION: EOs of L. alba and C. lanceolatus exhibited significant biological activity on the mortality and reproductive behaviour of pulse beetle. Based on their high LD(50) values, the oils could be safely recommended as non-mammalian toxic fumigants in management strategies for pulse beetle.

Pharmacogenomic landscape of COVID-19 therapies from Indian population genomes.

Aim: Numerous drugs are being widely prescribed for COVID-19 treatment without any direct evidence for the drug safety/efficacy in patients across diverse ethnic populations. Materials & methods: We analyzed whole genomes of 1029 Indian individuals (IndiGen) to understand the extent of drug-gene (pharmacogenetic), drug-drug and drug-drug-gene interactions associated with COVID-19 therapy in the Indian population. Results: We identified 30 clinically significant pharmacogenetic variants and 73 predicted deleterious pharmacogenetic variants. COVID-19-associated pharmacogenes were substantially overlapped with those of metabolic disorder therapeutics. CYP3A4, ABCB1 and ALB are the most shared pharmacogenes. Fifteen COVID-19 therapeutics were predicted as likely drug-drug interaction candidates when used with four CYP inhibitor drugs. Conclusion: Our findings provide actionable insights for future validation studies and improved clinical decisions for COVID-19 therapy in Indians.

Genetic epidemiology of autoinflammatory disease variants in Indian population from 1029 whole genomes.

BACKGROUND: Autoinflammatory disorders are the group of inherited inflammatory disorders caused due to the genetic defect in the genes that regulates innate immune systems. These have been clinically characterized based on the duration and occurrence of unprovoked fever, skin rash, and patient's ancestry. There are several autoinflammatory disorders that are found to be prevalent in a specific population and whose disease genetic epidemiology within the population has been well understood. However, India has a limited number of genetic studies reported for autoinflammatory disorders till date. The whole genome sequencing and analysis of 1029 Indian individuals performed under the IndiGen project persuaded us to perform the genetic epidemiology of the autoinflammatory disorders in India. RESULTS: We have systematically annotated the genetic variants of 56 genes implicated in autoinflammatory disorder. These genetic variants were reclassified into five categories (i.e., pathogenic, likely pathogenic, benign, likely benign, and variant of uncertain significance (VUS)) according to the American College of Medical Genetics and Association of Molecular pathology (ACMG-AMP) guidelines. Our analysis revealed 20 pathogenic and likely pathogenic variants with significant differences in the allele frequency compared with the global population. We also found six causal founder variants in the IndiGen dataset belonging to different ancestry. We have performed haplotype prediction analysis for founder mutations haplotype that reveals the admixture of the South Asian population with other populations. The cumulative carrier frequency of the autoinflammatory disorder in India was found to be 3.5% which is much higher than reported. CONCLUSION: With such frequency in the Indian population, there is a great need for awareness among clinicians as well as the general public regarding the autoinflammatory disorder. To the best of our knowledge, this is the first and most comprehensive population scale genetic epidemiological study being reported from India.

Comparison of Intravenous Nalbuphine and Paracetamol on Maternal Hemodynamic Status, Neonatal APGAR Score, and Postoperative Pain given before Induction of General Anesthesia for Elective Cesarean Section.

BACKGROUND: Stress response to endotracheal intubation and surgery is associated with exaggerated hemodynamic response and an increase in catecholamine levels which is deleterious to both the mother and fetus. We aimed to compare the effects of intravenous nalbuphine and paracetamol on maternal hemodynamic status, neonatal APGAR score, and postoperative pain using the visual analog scale for elective cesarean section under general anesthesia. STUDY DESIGN: This was a prospective, randomized, double-blinded clinical study. MATERIALS AND METHODS: Sixty full-term pregnant patients, belonging to the American Society of Anaesthesiologist physical status Classes I and II, scheduled for elective cesarean section under general anesthesia were enrolled for the study. The patients were randomly allocated into two groups of 30 patients each to receive paracetamol (15 mg.kg- 1) in Group Pand nalbuphine (0.2 mg.kg-1) in Group N before induction of general anesthesia. Maternal heart rate, blood pressure, and oxygen saturation were recorded before infusion of study drugs, after induction, after intubation, and during surgery across all periods. APGAR score of neonates was recorded by a pediatrician. Time to reach visual analogue score-1 was recorded. RESULTS: Significant attenuation of maternal hemodynamic response was observed with nalbuphine compared to the paracetamol group (P < 0.05). The time to achieve visual analogue score-1 in the postoperative period was higher in the nalbuphine group. APGAR score at 1 min was significant between the groups and at 5 min, nonsignificant difference was observed (P > 0.05). CONCLUSION: Nalbuphine and paracetamol are effective in perioperative hemodynamic stability of mother and APGAR score of neonates. However, nalbuphine had better hemodynamic stability as compared to paracetamol with a comparable APGAR score at 5 min.

Non-ionic small amphiphile based nanostructures for biomedical applications.

Self-assembly of non-ionic amphiphilic architectures into nanostructures with defined size, shape and morphology has garnered substantial momentum in the recent years due to their extensive applications in biomedicine. The manifestation of a wide range of morphologies such as micelles, vesicles, fibers, tubes, and toroids is thought to be related to the structure of amphiphilic architectures, in particular, the choice of the hydrophilic and hydrophobic parts. In this review, we look at different types of non-ionic small amphiphilic architectures and the factors that influence their self-assembly into various nanostructures in aqueous medium. In particular, we focus on the explored structural parameters that guide the formation of various nanostructures, and the ways these structures can be used in applications ranging from drug delivery to cell imaging.

Bio-Inspired Preparation of Clay-Hexacyanoferrate Composite Hydrogels as Super Adsorbents for Cs.

A facile and low-cost fabrication route, inspired by the adhesive proteins secreted by mussels, has been developed to prepare a clay-based composite hydrogel (DHG(Cu)) containing hexacyanoferrate (HCF) nanoparticles for the selective removal of Cs+ from contaminated water. Initially, montmorillonite was exfoliated prior to coating with a thin layer of polydopamine (PDOPA) via the self-polymerization of dopamine. Mixing the composite (D-clay) with the HCF precursor, followed by the addition of copper ions, led to the self-assembly of the polymer-coated exfoliated clay nanosheets into a three-dimensional network and in situ growth of KCuHCF nanoparticles embedded within the gel structure. Analytical characterization verified the fabrication route and KCuHCF immobilization by a copper-ligand complexation. Rheology testing revealed the composite hydrogel to be elastic under low strain and exhibited reversible, self-healing behavior following high strain deformation, providing a good retention of KCuHCF nanoparticles in the membrane. The adsorbent DHG(Cu) showed a superior Cs+ adsorption capacity (∼173 mg/g), with the performance maintained over a wide pH range, and an excellent selectivity for Cs+ when dispersed in seawater at low concentrations of 0.2 ppm. On the basis of its excellent mechanico-chemical properties, the fabricated hydrogel was tested as a membrane in column filtration, showing excellent removal of Cs+ from Milli-Q water and seawater, with the performance only limited by the fluid residence time. For comparison, the study also considered other composite hydrogels, which were fabricated as intermediates of DHG(Cu) or fabricated with Fe3+ as the cross-linker and reactant for HCF nanoparticle synthesis.

Ultrafast removal of arsenic using solid solution of aero-gel based Ce1-XTixO2-Y oxide nanoparticles.

An aero-gel based solid solution of titanium and cerium oxide nanoparticles have been used for the first time for ultra fast and trace level removal of arsenic from water. The interconnected long range ordered mesoporous structure was observed from TEM analysis which has been verified as an essential facet for the fast removal of arsenic in this study. The HR-XRD spectra indicated the face centred cubic structure with Fm3¯m space group. Le-Bail refinement and Raman spectroscopy confirmed the formation of single phase solid solution of Ce1-XTixO2-Y oxide nanoparticles. The HR-XPS and FT-IR study indicated the surface complexation and partial oxidation of As(III) to As(V) via electron transfer mechanism by reduction of Ce(IV) to Ce(III) and Ti(IV) to Ti(III) simultaneously during adsorption process. The kinetics study demonstrated 99% removal of As(III) within 10 min of initiating the adsorption process. The effect of pH and interfering ions confirmed the wide range of applicability for solid solution of titania and cerium oxide nanoparticles over the different environmental conditions for the removal of arsenic. The adsorption capacity for our best adsorbent (Ce0.8Ti0.2O2-y) was found to be 2 × 105 mg kg-1 while the lowest concentration of water body system was 7 µg L-1 which is the minimum concentration of arsenic achieved by any metal oxide based adsorbent.

Maternal and severe anaemia in delivering women is associated with risk of preterm and low birth weight: A cross sectional study from Jharkhand, India.

BACKGROUND AND OBJECTIVES: Haemoglobin content is the well accepted indicator for anaemia assessment. The high prevalence of anaemia, maternal health care issues and adverse delivery outcome in Jharkhand, we investigated whether delivering women with anaemia would present a modifiable risk of preterm (PTB) and low birth weight (LBW). METHODS: A facility-based cross-sectional study involving pregnant women, with screening for pregnancy endpoints and haemoglobin assay, were conducted. Anaemia was classified according to World Health Organization's definition of anaemia in pregnancy. Confounding variables were adjusted in a logistic model. The adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were used for analyzing the association among maternal anaemia, PTB and LBW. RESULTS: We observed a high prevalence of anaemia (78.45%) in delivering women, whereas high prevalence of preterm birth (34.75%) and LBW (32.81%) in delivering women overall. In the adjusted analysis, overall anaemia in pregnancy was strongly associated with preterm birth (OR, 3.42; 95% CI, 1.98-5.88; P ≤ .0001) as compared to LBW (OR, 1.12; 95% CI, 0.65-1.61; P = .0003). The risk of PTB and LBW were dependent on the stratification of the anaemia group, as the strongest association was observed in severe (OR, 4.86) followed by mild (OR, 3.66) and moderate (OR, 3.18) anaemia in PTB; whereas risk of LBW was found in severe (OR, 2.5) followed by moderate (OR, 1.11) and mild (OR, 0.57) anaemia. The risk of PTB and LBW across six pregnancy haemoglobin groups were compared, haemoglobin of 10-10.9 g/dl (OR, 1.25) and ≤ 8 g/dl (OR, 1.03) have shown association with PTB and LBW, respectively. However, high haemoglobin concentration was not associated with either PTB or LBW. CONCLUSIONS: Anaemia in delivering women was associated with an elevated risk of PTB and LBW and the risk increased with the severity of anaemia in pregnant women.

Surfactant-free one-pot synthesis of CeO2, TiO2 and Ti@Ce oxide nanoparticles for the ultrafast removal of Cr(vi) from aqueous media.

Cerium oxide (CeO2), titanium oxide (TiO2) and titanium oxide impregnated with cerium oxide (Ti@Ce oxide) nanoparticles were synthesized using a simple one-pot surfactant-free method. The synthesized adsorbents were tested against the removal of Cr(vi) from aqueous medium. Comprehensive characterization methods like BET, XRD, SEM, EDAX, HR-TEM, SAED, HR-XPS and FT-IR were performed at different stages of the adsorption process and synthesis. A N2-BET study revealed the large surface area (268 m2 g-1) and pore size (6.8 nm) of CeO2 nanoparticles, which decreased after impregnation of titania. An XRD study demonstrated the phase transformation of TiO2 from the anatase phase to the rutile phase after the impregnation with CeO2 by lowering the phase transformation temperature from >550 °C to 400 °C. Ti0.3@Ce0.7 oxide nanoparticles showed 81% removal of Cr(vi) within 2.5 min of initiating the adsorption process while more than 92% removal of Cr(vi) was achieved within 10 min of adsorption. A HR-XPS study indicated the dual oxidation states of ceria and titania metals, which helped to convert the more toxic Cr(vi) ions to less toxic Cr(iii) ions during the adsorption process. The adsorption pattern depicted the monolayer behavior of Cr(vi) obeying the Redlich-Peterson isotherm and followed pseudo second-order kinetics. An intraparticle diffusion model disclosed the surface and pore resistance diffusion of Cr(vi) on the surface of adsorbents.

Aero-gel assisted synthesis of anatase TiO2 nanoparticles for humidity sensing application.

Aero-gel based one-pot synthesis of anatase phase TiO2 nanoparticles having a high surface area of 125 m2 g-1 has been reported in this work. The humidity sensing perfomance of the obtained porous TiO2 nanoparticles exhibits a quick response (2 s) and fast recovery (1.5 s), negligible hysteresis (<1%) and good stability in the 11-98%RH range. The relationship between %RH and resistance was found to be linear while the sensitivity increases with increase in %RH.

Evaluating the utility of syndromic case management for three sexually transmitted infections in women visiting hospitals in Delhi, India.

Utility of syndromic case management (SCM) in women visiting obstetrics & gynecology department needs to be evaluated as it is subjective and imperfect. Consequently, antibiotic resistance has accelerated along with increased risk of infection to the partners. To understand the effectiveness and/or inadequacies of SCM, 11000 women were recruited and examined by clinicians for infection by Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV), Bacterial vaginosis (BV) and others. Amongst these patients, 1797 (16.3%) reported vaginal discharge (VD). Other symptoms included: vaginitis (97%), cervicitis (75%), genital ulcers (60%), abnormal vaginal discharge (55%) and lower abdominal pain (48%). The patients were treated for single or co-infections using pre-packed National Aids Control Program III STI/RTI Kits. However, based on PCR diagnostics, 1453/1797 (81%) subjects were uninfected for NG/TV/CT. Amongst 344 (19%) infected patients, 257 (75%) carried infection with single pathogen (TV/NG/CT) while 87/344 (25%) were co-infected with multiple pathogens. Prevalence of TV, NG & CT was 4%, 7% and 8% respectively. Co-infection with CT + NG was highest, 51% (44/87), whereas, co-infection with CT + TV was 21% and NG + TV was 18% while co-infection with all three pathogens was 1.3%. We conclude that SCM is imprecise and successful intervention requires accurate and confirmatory diagnostic approach.

Vulval myiasis: An unusual presentation of a rare entity in an adolescent female.

Human myiasis refers to parasitic infestation of body tissues by larvae of several fly species. The entity has a simple management. Human myiasis is well-documented in the literature however genital myiasis in females is scarcely reported in the literature. We hereby report this entity in an adolescent female who presented with urinary retention and concomitant urinary tract infection.

Safety assessment of Zanthoxylum alatum Roxb. essential oil, its antifungal, antiaflatoxin, antioxidant activity and efficacy as antimicrobial in preservation of Piper nigrum L. fruits.

The investigation deals with antifungal, antiaflatoxin and antioxidant efficacy of Zanthoxylum alatum Roxb. essential oil (EO), its two major constituents and their comparison with five commonly used organic acid preservatives. The chemical profile of EO, characterized through GC and GC-MS analysis, revealed linalool (56.10%) and methyl cinnamate (19.73%) as major components. The EO, linalool and methyl cinnamate completely inhibited the growth of a toxigenic strain of A. flavus (LHP-10) as well as aflatoxin B(1) secretion at different concentrations. Methyl cinnamate was found to be more efficacious than EO, linalool and five organic acid preservatives, showing antifungal and antiaflatoxigenic efficacy at a low concentration (0.6 µl/ml) and the nature of its toxicity was fungicidal. However, EO showed strong antioxidant activity with an IC(50) value at 5.6 µl/ml. Moreover, EO was found to have negligible mammalian toxicity as its LD(50) value, determined through oral administration on mice, was calculated to be 6124µl/kg body weight during safety profile assessment. During in vivo investigation on fruit systems, the Zanthoxylum EO, when tested as fumigant, provided 66.27% and 86.33% protection respectively at 1.25 µl/ml and 2.5 µl/ml against fungi infesting Piper nigrum L. fruits demonstrating its practical efficacy as a plant based antimicrobial for post harvest application.

Efficacy of chemically characterized Piper betle L. essential oil against fungal and aflatoxin contamination of some edible commodities and its antioxidant activity.

The study investigates fungal contamination in some dry fruits, spices and areca nut and evaluation of the essential oil (EO) of Piper betle var. magahi for its antifungal, antiaflatoxigenic and antioxidant properties. A total of 1651 fungal isolates belonging to 14 species were isolated from the samples and Aspergillus was recorded as the dominant genus with 6 species. Eleven aflatoxin B(1) (AFB(1)) producing strains of A. flavus were recorded from the samples. Eugenol (63.39%) and acetyleugenol (14.05%) were the major components of 32 constituents identified from the Piper betle EO through GC and GC-MS analysis. The minimum inhibitory concentration (MIC) of P. betle EO was found 0.7 microl/ml against A.flavus. The EO reduced AFB(1) production in a dose dependent manner and completely inhibited at 0.6 microl/ml. This is the first report on efficacy of P. betle EO as aflatoxin suppressor. EO also exhibited strong antioxidant potential as its IC(50) value (3.6 microg/ml) was close to that of ascorbic acid (3.2 microg/ml) and lower than that of the synthetic antioxidants such as butylated hydroxytouene (BHT) (7.4 microg/ml) and butylated hydroxyanisole (BHA) (4.5 microg/ml). P. betle EO thus exhibited special merits possessing antifungal, aflatoxin suppressive and antioxidant characters which are desirable for an ideal preservative. Hence, its application as a plant based food additive in protection and enhancement of shelf life of edible commodities during storage and processing is strongly recommended in view of the toxicological implications by synthetic preservatives.

Chemical profile, antifungal, antiaflatoxigenic and antioxidant activity of Citrus maxima Burm. and Citrus sinensis (L.) Osbeck essential oils and their cyclic monoterpene, DL-limonene.

The study deals with antifungal, antiaflatoxigenic and antioxidant activity of Citrus maxima and Citrus sinensis essential oils (EOs) and their phytochemical composition. The EOs were obtained by hydrodistillation and their chemical profile was determined through GC and GC-MS analysis. Both the EOs and their 1:1 combination showed broad fungitoxic spectrum against different food contaminating moulds. The EOs and their combination completely inhibited aflatoxin B(1) (AFB(1)) production at 500 ppm, whereas, DL-limonene, the major component of EOs showed better antiaflatoxigenic efficacy even at 250 ppm. Both the oils exhibited antioxidant activity as DPPH free radical scavenger in dose dependent manner. The IC(50) for radical scavenging efficacy of C. maxima and C. sinensis oils were to be 8.84 and 9.45 microl ml(-1), respectively. The EOs were found non-mammalian toxic showing high LD(50) for mice (oral, acute). The oils may be recommended as safe plant based antimicrobials as well as antioxidants for enhancement of shelf life of food commodities by checking their fungal infestation, aflatoxin production as well as lipid peroxidation.