Implications of equivalent black carbon heterogeneity in south Indian high-altitude eco-sensitive region.

Large-scale representative source apportionment studies are uncommon, undermining source contribution studies in India, particularly in high-altitude locations. Kodaikanal is a high-altitude region in India's Western Ghats, with spatial heterogeneity of sources altering chemical complexity; thus, the associated implications are unknown. We conducted the campaign study REBER (Research on Equivalent Black Carbon Monitoring in an Eco-sensitive Region) at three Kodaikanal sites to understand local point sources, characteristics, and distribution of eBC during the winter-to-summer monsoon transition. For two main reasons: to understand the seasonal change of BC since the transition period has the lowest wind speeds and the highest particulate concentrations and is prone to high pollution events most often during seasonal transition months, and to study local pollution since the meridional monsoon and zonal winds in study region weaken whereby the transport of pollutants from ocean to land and vice versa is minimal. The results showed that the eBC mass concentration was 85% higher than in the previous study conducted by Bhaskar et al. (2018) during the monsoon transition period. To determine the ratio of fossil fuel and wood-burning sources, a real-time apportionment model of atmospheric eBC is used. The percentage of wood burning in the background location ranges from 21.12 to 88.98%. Wood burning leads in residential sites with 57.5 ± 7.3%, whereas fossil fuel contribution dominates traffic sites with 69.84 ± 10.2%. Fossil fuel contributions are significant in different characteristics of environments, ranging from 42.5 to 69.84%. The results of the conditional bivariate probability function (CBPF) analysis pointed out a competition between anthropogenic and natural sources to contribute as local sources to the monitoring stations. A scanning electron microscope (SEM) paired with an energy dispersive X-ray (EDX) analysis found that the particle size was 93% relatively large compared to other hill stations in India. The variation in the chemical constituents indicates that the particles originated from various sources.

Black carbon flux in terrestrial and aquatic environments of Kodaikanal in the Western Ghats, South India: Estimation, source identification, and implication.

Evolving Anthropocene epoch wields significant influence in altering atmospheric carbon, which affects the carbon cycle, leading to climate change. Understanding the carbon stock, fate, and transport across ecosystems are essential in determining India's carbon budget, hitherto, unavailable. In this study, we have analysed the stock, source, distribution, flux, and the relationship between terrestrial and aquatic black carbon over a high-altitude mountainous area in the Western Ghats region using the data collected from September 2019 to February 2021. Soil Organic Carbon (SOC) and Black Carbon (BC) are the highest in the forest region (SOC:23 ± 3 g of C/kg (dry weight (dw)), BC:6 ± 3 g/kg) and are the lowest in the urban region (SOC: 13 ± 2 g of C/kg (dw), BC:2 ± 1 g/kg). SOC is labile, whereas BC is non-labile. The BC/SOC ratio represents soil carbon lability. Topsoil BC/SOC ratios vary by land use and land cover, with urban areas having greater labile carbon pools than the forests. Dissolved BC (DBC) concentrations were most strongly correlated with bulk Dissolved Organic Carbon (DOC) concentrations in midstream (R = 0.6, p < 0.05), headwater streams (R = 0.3, p < 0.05) and to the soil bulk DBC (R = 0.3, p < 0.05), indicating the presence of transfer mechanism of soil to streams. The molecular associations revealed the presence of biolabile autochthonous compounds suggesting the crucial role land use and land cover play on watersheds. A positive relationship between DOC with seasonal hydrology and gradient significantly influences the DBC flux across regional streams. Intercomparison of observed terrestrial and aquatic carbon stocks with globally modelled data indicates an overestimation of regional-scale stock. These new findings have repercussions to policy framework on regional climate change. Further, the results suggest that a consistent quantification of BC and integration of regional, and global source-to-sink process are needed in order to understand and better quantify biogeochemical process cycles and associated climatic impacts.

Quantification of organic carbon and black carbon emissions, distribution, and carbon variation in diverse vegetative ecosystems across India.

Black Carbon (BC) and Organic Carbon (OC) are the principal chemical aerosol components generated during combustion, both of which play a key role in air pollution, human health and climate change. Several studies of OC and BC have been conducted over India to assess the contribution from household and fossil fuel-based sources; however, studies on their emissions and their contribution from forest and cropland fires are quite limited. To address this issue, as part of this research, we derived a vegetation burning-based inventory of BC and OC aerosols over India at a resolution of 250 m × 250 m. Using a consumed biomass technique, we estimated emissions based on updated emission factor estimates. During the fire season in India (March-June), the mean OC and BC emissions were 2.1 ± 5.2 × 1013 kg per year and 1.8 ± 4.4 × 1012 kg per year, respectively. Andhra Pradesh had the highest total carbonaceous aerosol emissions during the study period. Forest fires were prevalent in the northeastern states, while agricultural fires were prevalent in Gujarat, Chhattisgarh, Odisha, Madhya Pradesh, Bihar, Tripura, Uttar Pradesh, and Andhra Pradesh. The previous inventory, conducted at a coarser resolution (25 km × 25 km), overestimated open burning by 5 Mt. Our results were highly correlated with global bottom-up model values, especially the Fire Inventory (FINN). Our analysis showed that vegetative burning contributed 80.32% of the total carbon stock, with agricultural burning being the largest source of vegetative burning. Based on these findings, measures and strategies to control agricultural burning which would reduce significantly the total emissions of BC and OC with implications to improvement in air quality, human health and climate should be planned.

Diagnostic techniques of minimum-B ECR ion source plasma instabilities.

The performance of a minimum-B Electron Cyclotron Resonance Ion Source (ECRIS) is traditionally quantified by measuring the beam current and quality of the extracted ion beams of different charge state ions. The stability of the extracted ion beam currents has drawn more attention recently as the technology is pushing its limits toward higher ion charge states and beam intensities. The stability of the extracted beam is often compromised by plasma instabilities manifesting themselves as rapid oscillations of the beam currents in millisecond scale. This paper focuses on practical aspects of diagnostics techniques of the instabilities, showcases examples of instability-related diagnostics signals, and links them to the plasma physics of ECR ion sources. The reviewed techniques include time-resolved microwave emission diagnostics, bremsstrahlung measurements, direct measurement of electron and ion fluxes, measurement of the ion beam energy spread, and optical emission diagnostics. We list the advantages and disadvantages of each technique and outline the development needs of further diagnostics. Finally, we discuss the implications of the instabilities in both historical and forward-looking context of ECRIS development.

Applications of IoT for achieving sustainability in agricultural sector: A comprehensive review.

This research aims to achieve a holistic understanding of the current IoT scenario by conducting a comparative analysis of the prevailing literature regarding IoT applications in the agricultural domain. Also, it proposes a framework for IoT adoption in the case sector. A systematic literature review was conducted with a methodology that focused on scientific articles authored in the English language that were published in peer-reviewed journals in the last five years. Initially, 179 research papers were extracted from the SCOPUS database and finally, 82 relevant articles were considered for the study which were classified into various categories and studied thoroughly. Based on a comprehensive survey of the selected articles four research questions were identified and successfully addressed. The results highlighted that research efforts pertaining to IoT applications of agriculture have matured from their initial conceptual stage and now reached the implementation phase. Also, it was observed that Machine Learning based algorithms were utilized extensively in recent research studies. For the first time, an exhaustive study has been conducted holistically to comprehend the recent advances in the field of IoT applications for the agricultural sector.

Preliminary investigation of drug impurities associated with the anti-influenza drug Favipiravir - An insilico approach.

The role of repurposed or modified antiviral drugs has become more significant during the current global pandemic of SARS Covid-19. In the present study, four structurally analogous impurity molecules of antiviral drug Favipiravir are selected for preliminary computational investigation for assessing the structure-activity relationship. The optimized geometry and the electronic structures of the compounds are computed using Density Functional Theory as a precursor to evaluating their physical, chemical and spectral properties. The frontier orbitals analysis is performed to obtain global reactivity parameters namely, the chemical potential, absolute electronegativity, global softness, global hardness, electrophilicity, etc. The natural Bond Orbital (NBO) analysis and Mulliken analysis provided an understanding of the charge-transfer interactions of molecules. The possibilities of intermolecular interactions of the drug systems with the receptors are also visualized using the electrostatic potential maps (MEP) derived from the DFT computations. The physiochemical properties are assessed computationally using SwissADME webtool to correlate the structural aspects of the compounds with their biological responses. Useful parameters namely flexibility, lipophilicity, size, polarity, solubility and saturation were also computed to evaluate the therapeutic activity or drug-likeness.

Challenges, experiences, and postoperative outcomes in setting up first successful lung transplant unit in India.

BACKGROUND: Lung transplantation (LT) has emerged as a definitive cure for a plethora of end-stage lung diseases (ESLDs). With improvements in immune-suppression protocols, the posttransplantation survival rates have gone up. AIM: The study reported the initial experience of the India's single largest lung transplant program on clinicopathological profile, procedures, challenges encountered, and outcomes. SETTINGS AND DESIGN: A retrospective analysis was done from data available at three centers of Institute of Heart and Lung Transplant, Gleneagles Global Hospitals across Chennai, Bengaluru, and Mumbai. MATERIALS AND METHODS: A total of 132 patients underwent lung (single or bilateral) or combined heart and lung transplant between April 2017 and March 2020. All the participants had 30 days' follow-up. Postoperative complications, graft rejection, and 30-day mortality were reported. Kaplan-Meier survival analysis and logistic regression analysis were performed. STATISTICAL ANALYSIS USED: Kaplan-Meier survival and binary logistic regression was performed. RESULTS: Interstitial lung diseases, 65.91%, were the most common diagnosis. Bilateral LT (81.3%) was the most common type of LT performed. Grade III primary graft dysfunction was observed in 16 (12.1%). Distal airway stenosis (21.97%) was the most common complication followed by anastomotic stenosis (14.30%). Gram-negative bacterial sepsis (52%) was the leading cause of death. Cumulative probability of survival at 1 month was 0.85 (95% confidence interval [CI] 0.80-0.92), and at 1 year, it was 0.78 (95% CI, 0.72-0.86). CONCLUSION: This study establishes the fact that despite multiple challenges, LT is a viable option for selected patients with ESLDs in India and should encourage early referrals to a transplant center.

A toxicogenomic approach for the risk assessment of the food contaminant acetamide.

Acetamide (CAS 60-35-5) is detected in common foods. Chronic rodent bioassays led to its classification as a group 2B possible human carcinogen due to the induction of liver tumors in rats. We used a toxicogenomics approach in Wistar rats gavaged daily for 7 or 28 days at doses of 300 to 1500 mg/kg/day (mkd) to determine a point of departure (POD) and investigate its mode of action (MoA). Ki67 labeling was increased at doses ≥750 mkd up to 3.3-fold representing the most sensitive apical endpoint. Differential gene expression analysis by RNA-Seq identified 1110 and 1814 differentially expressed genes in male and female rats, respectively, following 28 days of treatment. Down-regulated genes were associated with lipid metabolism while up-regulated genes included cell signaling, immune response, and cell cycle functions. Benchmark dose (BMD) modeling of the Ki67 labeling index determined the BMD10 lower confidence limit (BMDL10) as 190 mkd. Transcriptional BMD modeling revealed excellent concordance between transcriptional POD and apical endpoints. Collectively, these results indicate that acetamide is most likely acting through a mitogenic MoA, though specific key initiating molecular events could not be elucidated. A POD value of 190 mkd determined for cell proliferation is suggested for risk assessment purposes.

Computational and spectral studies of 3,3'-(propane-1,3-diyl)bis(7,8-dimethoxy-1,3,4,5-tetrahydro-2H-benzo[d]azepin-2-one).

Detection and qualification of unknown impurities during commercial drug synthesis have been mandated by the regulatory authorities. 3,3'-(propane-1,3-diyl)bis(7,8-dimethoxy-1,3,4,5-tetrahydro-2H-benzo [d]azepin-2-one) in short IVA-9, is one such process-related impurity formed during the synthesis of cardiotonic drug Ivabradine. The structure and properties of this molecule have not been explored yet. A suggestive reaction route for the chance formation of IVA-9 during the commercial synthesis of parent drug molecule has been reported in this article. Further, the optimized geometry and vibrational studies have been computed using Gaussian 09. Experimental FTIR scan has also been performed and values show satisfactory consilience with the computational data. The frontier orbital energies and energy band gaps of the reaction fragments and products were computed. The evaluation of ADME parameters such as absorption, distribution, metabolism, and excretion are performed using SwissADME tool to assess the drug-likeness and medicinal chemistry friendliness. Six physiochemical parameters namely flexibility, lipophilicity, size, polarity, solubility and saturation and their critical limits are depicted using the bioavailability radar of the programme to provide insights into pharmacokinetic properties such as human gastrointestinal absorption (HIA), blood-brain-barrier (BBB) permeability, total polar surface area (TPSA) and inhibitor action to important cytochromes etc.

Identifying critical success factors to facilitate reusable plastic packaging towards sustainable supply chain management.

The objective of this research is to identify critical success factors (CSFs) of the reusable plastic packaging (RPP) system and to establish their interrelationship in the context of manufacturing industries. Fourteen CSFs were shortlisted by reviewing the literature and considering expert team inputs. To explore the mutual influence between the identified CSFs the Interpretive Structural Modeling (ISM) approach was applied. To strengthen link interpretation, ISM methodology was supported by the Total Interpretive Structural Modeling (TISM) approach. Further, to identify the factors with high driving power the Matrice d'Impacts Croisés Multiplication Appliqués à un Classement (MICMAC) analysis was employed. It was concluded that three CSFs namely, 'top management commitment' 'lean support,' and 'optimized inventory management' were the critical ones with high influential power. This study aims to help the decision-makers in developing effective strategies for the implementation of the RPP system in the case sector for achieving sustainability.

Catalytic Oxidation of 3-Arylbenzofuran-2(3 H)-ones with PCC-H5IO6: Syntheses of 3-Aryl-3-hydroxy/3-amido-3-arylbenzofuran-2(3 H)-ones.

A pyridinium chlorochromate (PCC)-mediated facile oxidative dimerization of 3-arylbenzofuran-2-ones at ambient temperature was developed which undergo oxidative cleavage to 3-aryl-3-hydroxy-benzofuran-2-ones with PCC at elevated temperatures. Finally, direct oxidation of 3-arylbenzofuran-2-ones to 3-aryl-3-hydroxy-benzofuran-2-ones was realized using a combination of PCC (10 mol %) and 2.0 equiv of H5IO6. The synthesized 3-aryl-3-hydroxy-benzofuranones were further converted to corresponding 3-amido-3-aryl-benzofuranones in high yields by Ritter reaction. Thus, the present protocol provides a nonconventional approach to C-3 hydroxylation of 3-arylbenzofuranones via their dimer using a catalytic amount of inexpensive chromium(VI) oxidant.

Tailoring the properties of mPEG-PLLA nanoparticles for better encapsulation and tuned release of the hydrophilic anticancer drug.

Gemcitabine is used as a first-line drug for treating many solid tumours. However, it suffers from a major drawback of strong side effects and short plasma half-life because of degradation by enzyme when administered intravenously. Polyesters and copolyesters are the most widely used and preferred class of biodegradable polymer. In the present work, efforts have been made to prepare poly(ethylene glycol) monomethoxy ether-poly(L-lactide) (mPEG-PLLA), a biodegradable amphiphilic copolymer with a view to improve the entrapment and tuned release of hydrophilic drug gemcitabine. The different mPEG-PLLA copolymers were synthesized with the varying ratios of mPEG and characterized by different techniques namely FTIR and 1H NMR spectroscopy, solution viscosity, differential scanning calorimetry (DSC) and gel permeation chromatography (GPC). Gemcitabine-loaded nanoparticles were prepared using mPEG-PLLA copolymers by two methods i.e. nanoprecipitation and double emulsion solvent evaporation. The nanoprecipitation method showed very less entrapment and polymer solubility in the acetone-water mixture leading to uncontrolled polymer precipitation. The difficulties encountered in the nanoprecipitation method were overcome with the help of the double emulsion (w/o/w) solvent evaporation technique. It has been observed from the results that biodegradable copolymer nanoparticles protect the drug from degradation and also help in controlling the release of encapsulated drug. The properties of nanoparticles can be tailored by varying the composition of mPEG in order to get improved entrapment efficiency and desired drug release. The nanoparticles were assessed for their in vitro cytotoxicity (MTT and FACS) and cellular uptake (fluorescence microscopy) study which showed very promising results. Nanoparticles were also studied for their in vivo release after intravenous administration to Wistar albino rats, which successfully showed controlled drug release for more than 14 days.

In silico analysis of consequences of non-synonymous SNPs of Slc11a2 gene in Indian bovines.

The aim of our study was to analyze the consequences of non-synonymous SNPs in Slc11a2 gene using bioinformatic tools. There is a current need of efficient bioinformatic tools for in-depth analysis of data generated by the next generation sequencing technologies. SNPs are known to play an imperative role in understanding the genetic basis of many genetic diseases. Slc11a2 is one of the major metal transporter families in mammals and plays a critical role in host defenses. In this study, we performed a comprehensive analysis of the impact of all non-synonymous SNPs in this gene using multiple tools like SIFT, PROVEAN, I-Mutant and PANTHER. Among the total 124 SNPs obtained from amplicon sequencing of Slc11a2 gene by Ion Torrent PGM involving 10 individuals of Gir cattle and Murrah buffalo each, we found 22 non-synonymous. Comparing the prediction of these 4 methods, 5 nsSNPs (G369R, Y374C, A377V, Q385H and N492S) were identified as deleterious. In addition, while tested out for polar interactions with other amino acids in the protein, from above 5, Y374C, Q385H and N492S showed a change in interaction pattern and further confirmed by an increase in total energy after energy minimizations in case of mutant protein compared to the native.

The effect of aerosol optical depth on rainfall with reference to meteorology over metro cities in India.

Rainfall is a key link in the global water cycle and a proxy for changing climate; therefore, proper assessment of the urban environment's impact on rainfall will be increasingly important in ongoing climate diagnostics and prediction. Aerosol optical depth (AOD) measurements on the monsoon seasons of the years 2008 to 2010 were made over four metro regional hotspots in India. The highest average of AOD was in the months of June and July for the four cities during 3 years and lowest was in September. Comparing the four regions, Kolkata was in the peak of aerosol contamination and Chennai was in least. Pearson correlation was made between AOD with climatic parameters. Some changes in the parameters were found during drought year. Temperature, cloud parameters, and humidity play an important role for the drought conditions. The role of aerosols, meteorological parameters, and their impacts towards the precipitation during the monsoon was studied.

Comparison of outcome in Jehovah's Witness patients in cardiac surgery: an Australian experience.

INTRODUCTION: Despite the advances in modern medicine, cardiac surgery remains associated with significant amounts of blood transfusion and is responsible for nearly 20% of all transfusions in Australasia. Progressive advances in perfusion technology and perioperative supportive management have made it possible for members of the Jehovah's Witnesses (JW) religious group to undergo open cardiac operations with remarkable safety. This study systematically compares the operative mortality and early clinical outcome after cardiac surgery in JWs. METHODS AND MATERIALS: Data was obtained from the cardiac surgery and intensive care unit databases from January 2002 to December 2005. A total of 5353 patients who underwent cardiac surgical procedures including coronary artery bypass grafting with cardiopulmonary bypass (n=4041) and valvular heart surgery (n=2287) were assessed in this study. Of the 5353 patients 49 patients refused blood and blood products because of their religious beliefs. Models were constructed to determine the association between JWs and non-JWs and three outcomes: (1) operative mortality, (2) postoperative variables and (3) length of stay in intensive care unit. Propensity scores were computed from these models and used to match JWs with non-JWs. RESULTS: There were minimal differences in the baseline patient demographic characteristics between the two groups. Haemoglobin and haematocrit levels were higher in JWs both before (13.7g/dL vs 12.8g/dL; P=0.01, and 40.0% vs 39.2%; P=0.08) and after (10.8g/dL vs 9.9g/dL; P=.003, and 34.0% vs 30.9%; P=.001) surgery. Jehovah's Witnesses experienced significantly less bleeding, almost half compared to the control group, with P<0.001. No differences were found in the adjusted and unadjusted operative mortality or intensive care unit and postoperative length of stay between the two groups. CONCLUSION: This study concurs with the international published data that outcomes for JW patients who undergo cardiac surgery are similar to those who receive transfusion. Every appropriate opportunity to reduce the use of allogeneic blood products.

Ionic and heavy metal composition of respirable particulate in Madurai, India.

Airborne particulate matter (PM(10)) was collected for a period of 1 year at six locations in Madurai city, India. The chemical analyses on PM(10) samples were carried out for the estimation of heavy metals and ions using atomic absorption spectroscopy and ion chromatography respectively. The average PM(10) concentrations varied from 97.2 to 152.5 microg/m(3), which were found to be below the Indian air quality standards. While industrial areas had the highest concentrations of heavy metals such as Fe, Zn and Cr and also the SO(4)(2-) ions, traffic areas with relatively higher traffic densities in the city endured highest concentrations of Cd and the NO(3)(-) ion. As gaseous pollutants serve as precursors of ionic particles in the atmospheric environment, gaseous pollution control is necessitated along with particulate with special reference to heavy metal and ion pollution abatement for the sustainable development of Madurai city.

Engineering ascorbate peroxidase activity into cytochrome c peroxidase.

Cytochrome c peroxidase (CCP) and ascorbate peroxidase (APX) have very similar structures, and yet neither CCP nor APX exhibits each other's activities with respect to reducing substrates. APX has a unique substrate binding site near the heme propionates where ascorbate H-bonds with a surface Arg and one heme propionate (Sharp et al. (2003) Nat. Struct. Biol. 10, 303-307). The corresponding region in CCP has a much longer surface loop, and the critical Arg residue that is required for ascorbate binding in APX is Asn in CCP. In order to convert CCP into an APX, the ascorbate-binding loop and critical arginine were engineered into CCP to give the CCP2APX mutant. The mutant crystal structure shows that the engineered site is nearly identical to that found in APX. While wild-type CCP shows no APX activity, CCP2APX catalyzes the peroxidation of ascorbate at a rate of approximately 12 min (-1), indicating that the engineered ascorbate-binding loop can bind ascorbate.

Investigations of oxidative stress, antioxidant response, and protein binding in chlorpyrifos exposed rat neuronal PC12 cells.

ABSTRACT Chlorpyrifos (CPF) is a widely used organophosphate insecticide. In addition to its known properties of cholinesterase inhibition, the production of reactive oxygen species (ROS) has been suggested as a possible toxic mechanism. To investigate CPF-generated ROS, rat neuronal PC12 cells were exposed to CPF concentrations of 0 to 5000 mug/mL in Krebs buffered media (KRH), KRH + 4% bovine serum albumin (BSA), and KRH + 25 muM of the antioxidant Trolox for 0 to 5 h. Paraquat served as a positive control for ROS. The fluorescent probe 2,7-dichlorodihydro-fluorescein and the MTS assay were used to measure ROS and cytotoxicity, respectively. Examinations into CPF-albumin binding were also conducted. CPF was not strongly cytotoxic to PC12 cells, causing only mild cytotoxicity at 5000 mug/ml. In KRH media, CPF-generated ROS was observed at 4 and 5 h at 500 and 1000 mug/mL, and at 1 to 5 h at 5000 mug/mL CPF. In KRH + 4% BSA, ROS was seen only at 5 h in 5000 mug/mL CPF. Trolox significantly reduced CPF- and paraquat-induced ROS. Calculated CPF-albumin binding at 1, 10, and 100 mug/mL CPF in 4% BSA was 96%, 75%, and 15%. These data show CPF at >/=500 mug/mL induced ROS in PC12 cells, but the addition of the antioxidant Trolox and 4% BSA dramatically reduced ROS levels.

Structural identification and characterization of potential impurities of pantoprazole sodium.

Six impurities in pantoprazole sodium bulk drug substance were detected by a simple high performance liquid chromatographic method (HPLC) whose area percentage ranged from approximately 0.05 to 0.34%. Liquid chromatography-mass spectrometry (LC-MS) was performed to identify the molecular weight of the impurities. A thorough study was undertaken to characterize these impurities. These impurities were synthesized, subsequently characterized and were co-injected with the sample containing impurities and found the retention time match of the spiked impurities. Based on their spectral data (IR, NMR and MS), these impurities were characterized as; 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]thio]-1H-benzimidazole (Impurity-I); 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]sulfonyl]-1H-benzimidazole (Impurity-II); 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-1-oxide-2-pyridinyl)methyl]sulfonyl]-1H-benzimidazole (Impurity-III); 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]thio]-1-((3,4-dimethoxy-2-pyridinyl)methyl)-1H-benzimidazole (Impurity-IV); 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]sulfinyl]-1-((3,4-dimethoxy-2-pyridinyl)methyl)-1H-benzimidazole (Impurity-V); 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-1-oxide-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole (Impurity-VI). The formation of these impurities was proposed. The structure of the Impurity-II was unambiguously confirmed by single crystal X-ray diffraction (XRD) studies.