Publications by authors named "Priyanka Sharma"

306 Publications

COVID-19 vaccination in India: An ethical perspective.

Diabetes Metab Syndr 2021 Oct 15;15(6):102314. Epub 2021 Oct 15.

Department of Community Medicine, Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi, India. Electronic address:

Background And Aims: COVID-19 had put world to a standstill with enormous morbidity and mortality. Vaccines' development against this provided a beacon of hope. India approved different vaccines under emergency use authorization but distribution of vaccines and vaccination of huge population was a challenging task. We attempted to review the vaccination program from an ethics perspective.

Methods: The core ethical principles of healthcare and other tenets put forth in discussion papers on addressing ethical issues in pandemic influenza planning, ethical considerations in developing a public health response to pandemic influenza and World Health Organization (WHO) Scientific Advisory Group for Emergencies values framework for the allocation and prioritization of COVID-19 vaccination were used to identify the ethical concerns in the vaccination program of the country. Relevant ministry guidelines, documents, websites etc., were accessed.

Results: The program tried addressing many of the ethical principles laid out in various international documents. Approving indigenously produced vaccines upheld the principle of utility while prioritizing health care workers for vaccination was an example of reciprocity. However, vaccine approval without availability of trial results in public domain raised apprehensions and lacked transparency. Lack of well-defined mechanism to facilitate vaccination for socially disadvantaged groups compromises equity.

Conclusion: Overall, the program fared well on most aspects of ethical principles, but there were few gaps which still exist. These should be taken care of as the country advances further into vaccination program to garner enhanced public trust in the scientific, regulatory and administrative authorities.
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http://dx.doi.org/10.1016/j.dsx.2021.102314DOI Listing
October 2021

Computational investigation of drug bank compounds against 3C-like protease (3CL) of SARS-CoV-2 using deep learning and molecular dynamics simulation.

Mol Divers 2021 Oct 12. Epub 2021 Oct 12.

Computational Biology and Biotechnology Laboratory, Department of Botany, Soban Singh Jeena University, Almora, Uttarakhand, 263601, India.

Blocking the main replicating enzyme, 3 Chymotrypsin-like protease (3CL) is the most promising drug development strategy against the SARS-CoV-2 virus, responsible for the current COVID-19 pandemic. In the present work, 9101 drugs obtained from the drug bank database were screened against SARS-CoV-2 3CL prosing deep learning, molecular docking, and molecular dynamics simulation techniques. In the initial stage, 500 drug-screened by deep learning regression model and subjected to molecular docking that resulted in 10 screened compounds with strong binding affinity. Further, five compounds were checked for their binding potential by analyzing molecular dynamics simulation for 100 ns at 300 K. In the final stage, two compounds {4-[(2s,4e)-2-(1,3-Benzothiazol-2-Yl)-2-(1h-1,2,3-Benzotriazol-1-Yl)-5-Phenylpent-4-Enyl]Phenyl}(Difluoro)Methylphosphonic Acid and 1-(3-(2,4-dimethylthiazol-5-yl)-4-oxo-2,4-dihydroindeno[1,2-c]pyrazol-5-yl)-3-(4-methylpiperazin-1-yl)urea were screened as potential hits by analyzing several parameters like RMSD, Rg, RMSF, MMPBSA, and SASA. Thus, our study suggests two potential drugs that can be tested in the experimental conditions to evaluate the efficacy against SARS-CoV-2. Further, such drugs could be modified to develop more potent drugs against COVID-19.
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http://dx.doi.org/10.1007/s11030-021-10330-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8506074PMC
October 2021

Maternal Transmission of Human OGG1 Protects Mice Against Genetically- and Diet-Induced Obesity Through Increased Tissue Mitochondrial Content.

Front Cell Dev Biol 2021 15;9:718962. Epub 2021 Sep 15.

Rutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition, and Health, Rutgers University, New Brunswick, NJ, United States.

Obesity and related metabolic disorders are pressing public health concerns, raising the risk for a multitude of chronic diseases. Obesity is multi-factorial disease, with both diet and lifestyle, as well as genetic and developmental factors leading to alterations in energy balance. In this regard, a novel role for DNA repair glycosylases in modulating risk for obesity has been previously established. Global deletion of either of two different glycosylases with varying substrate specificities, Nei-like endonuclease 1 (NEIL1) or 8-oxoguanine DNA glycosylase-1 (OGG1), both predispose mice to diet-induced obesity (DIO). Conversely, enhanced expression of the human gene renders mice resistant to obesity and adiposity. This resistance to DIO is mediated through increases in whole body energy expenditure and increased respiration in adipose tissue. Here, we report that expression also confers resistance to genetically-induced obesity. While Agouti obese () mice are hyperphagic and consequently develop obesity on a chow diet, expression in mice ( ) prevents increased body weight, without reducing food intake. Instead, obesity resistance in mice is accompanied by increased whole body energy expenditure and tissue mitochondrial content. We also report for the first time that OGG1-mediated obesity resistance in both the model and DIO model requires maternal transmission of the transgene. Maternal, but not paternal, transmission of the transgene is associated with obesity resistance and increased mitochondrial content in adipose tissue. These data demonstrate a critical role for OGG1 in modulating energy balance through changes in adipose tissue function. They also demonstrate the importance of OGG1 in modulating developmental programming of mitochondrial content and quality, thereby determining metabolic outcomes in offspring.
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http://dx.doi.org/10.3389/fcell.2021.718962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480284PMC
September 2021

Evaluating Serum Thymidine Kinase 1 in Patients with Hormone Receptor-Positive Metastatic Breast Cancer Receiving First-line Endocrine Therapy in the SWOG S0226 Trial.

Clin Cancer Res 2021 Sep 14. Epub 2021 Sep 14.

University of Michigan Rogel Cancer Center, Ann Arbor, Michigan.

Purpose: Serum thymidine kinase 1 (sTK1) activity is associated with poor prognosis in metastatic breast cancer (MBC). We assessed the prognostic effect of sTK1 in patients with hormone receptor-positive MBC treated on a prospective randomized trial of anastrozole (A) versus A plus fulvestrant (A + F).

Experimental Design: sTK1 was assessed in 1,726 serums [baseline (BL), cycles 2, 3, 4, and 7] using the DiviTum assay. A prespecified cutoff of ≥200 Du/L was considered high. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier, log-rank tests, and Cox regression.

Results: BL sTK1 was elevated in 171 (40%) of 432 patients. Patients with high versus low BL sTK1 had significantly worse PFS [median 11.2 vs. 17.3 months, HR = 1.76; 95% confidence interval (CI; 1.43-2.16); < 0.0001] and OS [median 30 vs. 58 months, HR = 2.38; 95% CI (1.91-2.98); < 0.0001]. OS was significantly better for patients with high sTK1 who did not have prior adjuvant tamoxifen and who received A + F versus A alone [median 46 vs. 21 months, HR = 0.58; 95% CI (0.38-0.87); = 0.0087]. Patients with low sTK1 had no difference in outcomes by therapy ( = 0.44). At serial timepoints, high versus low sTK1 had significantly worse subsequent PFS and OS [at cycle 2: PFS HR = 1.70, 95% CI (1.34-2.17); < 0.0001, OS HR = 2.51, 95% CI (1.93-3.26); < 0.0001].

Conclusions: High sTK1 at BL and subsequent timepoints is associated with worse prognosis in patients with MBC starting first-line endocrine therapy (ET). Patients with low sTK1 at BL have comparable outcomes on single-agent or combination ET.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-1562DOI Listing
September 2021

Phytometabolite profiling of Coronil, a herbal medicine for COVID-19, its identification by mass-spectroscopy and quality validation on liquid chromatographic platforms.

J Sep Sci 2021 Sep 12. Epub 2021 Sep 12.

Drug Discovery and Development Division, Patanjali Research Institute, NH-58, Haridwar, Uttarakhand, 249405, India.

Coronil is a tri-herbal medicine consisting of immunomodulatory herbs, Withania somnifera, Tinospora cordifolia, and Ocimum sanctum. The formulation has been developed specifically as the supporting measure for COVID-19. Current investigation is aimed to identify the phytoconstituents in Coronil utilizing ultra-performance liquid chromatography-mass spectrometry coupled with quadrapole time of flight and to establish its quality standardization using high-performance liquid chromatography and high performance thin layer chromatography. Out of 52 identified compounds, cordifolioside A, magnoflorine, rosmarinic acid, palmatine, withanoside IV, withanoside V, withanone, betulinic acid, and ursolic acid were quantified in 15 different batches of Coronil on validated high-performance liquid chromatography method. Similarly, withanoside IV, withaferin A, magnoflorine, palmatine, rosmarinic acid, and ursolic acid were analyzed on high performance thin layer chromatography. Methods were validated as per the International Council for Harmonization guidelines. These methods were specific, reproducible, accurate, precise, linear (r > 0.99), and percent recoveries were within the prescribed limits. The content uniformity of Coronil was ascertained using Fourier transform infrared spectroscopy. Results indicated that, validated methods were fit for their intended use and the analytical quality of Coronil was consistent across the batches. Taken together, these developed methods could drive the analytical quality control of herbal medicines such as Coronil, and other formulations containing similar chemical profiles.
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http://dx.doi.org/10.1002/jssc.202100499DOI Listing
September 2021

Comparative evaluation of nasal and alveolar changes in complete unilateral cleft lip and palate patients using intraoral and extraoral nasoalveolar molding techniques: randomized controlled trial.

J Korean Assoc Oral Maxillofac Surg 2021 Aug;47(4):257-268

Department of Pediatric and Preventive Dentistry, Government Dental College & Hospital, Nagpur, India.

Objectives: Cleft lip and palate is a common congenital anomaly that impairs the aesthetics, speech, hearing, and psychological and social life of an individual. To achieve good aesthetic outcomes, presurgical nasoalveolar molding (NAM) has become important. Currently, the intraoral NAM technique is widely practiced. Numerous modifications have been made to intraoral NAM techniques, but the original problem of compliance leading to discontinuation of treatment remains unsolved. Therefore, the present study compared an extraoral NAM technique with the intraoral NAM technique.

Materials And Methods: Twenty infants with complete unilateral cleft lip and palate were included and divided into two equal groups. Group A received the intraoral NAM technique, and Group B received the extraoral NAM technique. Pre- and postoperative extraoral and intraoral measurements were recorded.

Results: Groups A and B did not differ significantly in any extraoral or intraoral parameter.

Conclusion: The extraoral NAM technique is as effective as the intraoral NAM technique in achieving significant nasal and alveolar changes in com-plete unilateral cleft lip and palate patients. Additionally, it reduces the need for frequent hospital visits for activation and the stress associated with the insertion and removal of the intraoral NAM plate, thereby improving compliance.
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http://dx.doi.org/10.5125/jkaoms.2021.47.4.257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408650PMC
August 2021

IMPACT OF COVID-19 ON MENTAL HEALTH AND AGING.

Saudi J Biol Sci 2021 Aug 4. Epub 2021 Aug 4.

Feroz Gandhi Institute of Engineering & Technology, Raebareli-229001, Uttarpradesh.

The potential ramifications of the COVID-19 pandemic on the population's mental health are a rising global concern. Both at the individual and community level, the erratic and uncertain COVID-19 outbreak has the prospective to exhibit a detrimental effect on psychological health and aging. At present, various measures are dedicated to the parameters like awareness of epidemiology, clinical aspects, mode of transmission, counteracting the spread of the infection, and public health problems, although this initiative has neglected critical mental health concerns. This study is to investigate the outbreak to study the level of harmful effects on mental health and its crosstalk with aging. Global execution of preventive, control measures and resilience establishment are challenging factors whereas reformed lifestyle such as lockdown, coping with self-isolation, quarantine, social distancing, and post-traumatic stress disorders are alarming. Hallmarks of aging which interact with each other, have been suggested to affect the healthspan in aged adults, possibly due to attenuated immunity. Among various hallmarks, we concentrated on those that show direct or indirect interaction with viral infections, comprising inflammation, genomic instability, impaired mitochondrial function, epigenetic modification, telomere attrition, and damaged autophagy. These hallmarks possibly contribute to the elicited pathophysiological responses to SARS-CoV-2 and may add an additive risk of accelerated aging post-recovery among aged adults. Here, the role of antiaging drug candidates that require main consideration in COVID-19 research is discussed briefly. In the later future, it can emerge as a potential therapeutic approach in the treatment of patients with severe infection.
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http://dx.doi.org/10.1016/j.sjbs.2021.07.087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336988PMC
August 2021

Glabridin attenuates paracetamol-induced liver injury in mice via CYP2E1-mediated inhibition of oxidative stress.

Drug Chem Toxicol 2021 Jul 7:1-9. Epub 2021 Jul 7.

PK-PD, Toxicology and Formulation Division, CSIR-Indian Institute of Integrative Medicine, Jammu, Jammu and Kashmir, India.

CYP2E1 plays a crucial role in the bio-activation of toxic substances leading to liver damage. In this context, CYP2E1 converts paracetamol (PCM) to N-acetyl-p-benzoquinone imine (NAPQI), which is prone to cause hepatotoxicity. Hence, we aimed to explore the protective effect of glabridin on widely used PCM-induced liver injury model in the present study and, after that, correlated with the role of CYP2E1 toward its efficacy. Glabridin was isolated from and characterized before the investigation in an mice model of PCM-induced liver injury. Glabridin after oral treatment at 5-20 mg/kg showed a considerable improvement in serum biochemical parameters (ALT and AST) and oxidative stress markers (MDA, GSH, SOD, and catalase) in comparison to only PCM-treatment. Histopathological examination of the liver depicted that glabridin exhibited substantial protection from PCM-induced liver injury compared to the disease control group. Significant down-regulation of CYP2E1 protein and its mRNA expression levels were observed in the glabridin-treated groups compared to PCM-induced respective elevation of CYP2E1. Moreover, activation of NF-κB was significantly inhibited by glabridin. Therefore, glabridin has the potential to protect PCM-induced liver injury through CYP2E1 inhibition-mediated normalization of oxidative stress. Further research is warranted to establish glabridin as a phytotherapeutics for liver protection for which no effective and safe oral drug is available to date.
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http://dx.doi.org/10.1080/01480545.2021.1945004DOI Listing
July 2021

identification of antidiabetic target for phytochemicals of and mechanistic insights by molecular dynamics simulations.

J Biomol Struct Dyn 2021 Jul 6:1-18. Epub 2021 Jul 6.

Department of Botany, D.S.B. Campus, Kumaun University, Nainital, Uttarakhand, India.

The leaves and fruits of (L.) have antidiabetic activity. However, the mode of action and molecules having antidiabetic activity are not known. Hence, we conducted molecular docking of phytochemicals with various molecular antidiabetic targets to find the same. Docking prioritized Dipeptidyl peptidase-4 (DPP-4) as the main target for phytochemicals of . DPP-4 inactivates intestinal peptides, glucagon-like peptide-1 (GLP-1), and Gastric inhibitory polypeptide (GIP). GLP-1 and GIP stimulate a decline in blood glucose levels, but DPP-4 inhibits their functions resulting high level of glucose. Hence inhibiting the activity of DPP-4 is a well-known strategy to treat Type 2 diabetes. Therefore, to find a mechanism that may be involved to act as a natural inhibitor of DPP-4, we screened five phytochemicals out of seventy-three based on Virtual Screening, ADMET Drug-likeness analysis, and PAINS filtering. Further, all five phytochemicals, i.e. Aegeline, Citral, Marmesinin, Auraptene, β-Bisabolene, and reference compound subjected MDS for analyzing the stability of docked complexes to assess the fluctuation and conformational changes during protein-ligand interaction. The values of RMSD, RG, RMSF, SASA, and Gibbs energy revealed the good stability of these phytochemicals in the active site pocket of DPP-4 in comparison to reference. Additionally, we have done the pharmacophore analysis, which revealed many common pharmacophore features between screened phytochemicals of and reference molecule. Our results show that these phytochemicals are potential antidiabetic candidates and can be further modified and evaluated to develop more effective antidiabetic drugs against DPP-4 to treat Type 2 Diabetes. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2021.1944910DOI Listing
July 2021

Identification of Circular RNAs by Multiple Displacement Amplification and Their Involvement in Plant Development.

Methods Mol Biol 2021 ;2362:69-91

Department of Plant Biotechnology, School of Biotechnology, Madurai Kamaraj University, Madurai, India.

With the innovative knowledge and bioinformatics tools in the identification and characterization of noncoding RNAs, circular RNA (circRNA) is added as a new member to the noncoding RNAs family. CircRNA enrichment by rRNA depletion/RNase R or poly-A removal/RNase R treatment followed by NGS analysis is the most frequently adopted method for circular RNA identification and characterization. In this chapter, we describe the multiple displacement amplification (MDA) as a convenient method to augment the identification of even the abysmally expressed circular RNAs at low sequencing depth. Total RNA, extracted at three different developmental stages of rice, is subjected to RiboMinus and RNase R treatment to deplete the linear RNAs. The enriched circular RNAs are reverse transcribed with random hexamers. The resulting cDNA is subjected to phi29 DNA polymerase amplification using exo-resistant random pentamers to yield high molecular weight dsDNA product, followed by Illumina sequencing at ten million paired end reads per sample. The sequence analysis yielded a promising number of circRNAs with the appreciable inclusion of differentially regulated and minimally expressed circRNAs at a comparatively reduced cost.
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http://dx.doi.org/10.1007/978-1-0716-1645-1_4DOI Listing
January 2021

Generation of Transgenic Rice Expressing CircRNA and Its Functional Characterization.

Methods Mol Biol 2021 ;2362:35-68

Department of Plant Biotechnology, School of Biotechnology, Madurai Kamaraj University, Madurai, India.

Circular RNA (CircRNA) is yet another vital addition to the noncoding RNA family. They are mainly derived by fusion of downstream 3' splice donor with upstream 5' splice acceptor by a noncanonical form of alternative splicing mechanism called backsplicing. An array of functional aspects of these circRNAs has been reported in animal systems. However, functional investigation of circRNA in plants is very limited. In this chapter, we described a methodological outline to study the circRNA biogenesis and to characterize its function(s). Sequence of a newly identified Oryza sativa Indica circRNA flanked by complementary repeat sequences of a rice intron was assembled to yield a circRNA expression cassette. This cassette can be cloned into any plant expression vector which has a suitable promoter (CaMV 35S or ubiquitin promoter) and terminator, and can be used for any circRNA-mediated functional studies. Subsequent agroinfection of rice calli with this cassette yielded circRNA expressing transgenic plants. These transgenic plants were used to establish a correlation between the expressing circRNA, parental gene, and interacting miRNAs. Moreover, effect of circRNA overexpression on plant phenotype under various stress conditions can be studied using these transgenic plants. Also, RNA pull-down assay can be performed to identify the circRNA interacting proteins and the expression of these RBPs can also be studied from these transgenic plants.
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http://dx.doi.org/10.1007/978-1-0716-1645-1_3DOI Listing
January 2021

Dose-Dependent Oxidative Damage in Erythrocytes and Hepatic Tissue of Wistar Rats Concurrently Exposed with Arsenic and Quinalphos: a Subacute Study.

Biol Trace Elem Res 2021 Jun 29. Epub 2021 Jun 29.

Division of Veterinary Pharmacology and Toxicology, Faculty of Veterinary Sciences and Animal Husbandry, SKUAST-J, R S Pura, 181102, Jammu & Kashmir, India.

Concurrent exposure to a multitude of environmental toxicants pose serious health hazard to humans and animals. The present investigation was conceptualized to determine deleterious effects of concomitant subacute arsenic and quinalphos exposure on antioxidant responses of liver and erythrocytes of Wistar rats. Fifty-four Wistar rats were divided into nine groups with six animals in each. Animals were exposed to either quinalphos (1/100 and 1/10 of LD) through oral gavage daily or arsenic (50 and 100 ppb) in drinking water alone and in combination for 28 days. While treatment with different toxicants alone also significantly reduced hemoglobin concentration, hepatic biomarkers and levels of antioxidant parameters as compared with control values, concomitant exposure significantly (P < 0.05) elevated levels of hepatic transaminases and alkaline phosphatase. Moreover, along with significant depletion in activities of SOD, CAT, TTH, AChE, and enzymes of glutathione complex, a significant enhancement of lipid peroxidation was also recorded in liver and erythrocytes in co-exposed animals in a dose-dependent manner when compared with exposure to individual toxicant. More severe alterations occurred in hepatic histo-architecture of rats receiving combined treatment as compared with those treated with either toxicant. Results indicated that oxidative damage in erythrocytes was more than that of the liver of rats on concomitant exposure of arsenic and quinalphos in a dose-dependent manner. In nutshell, our results revealed that combined treatment of quinalphos with arsenic potentiated toxic effects of either toxicant on antioxidant machinery of liver and erythrocytes and hepatic histomorphology of exposed Wistar rats.
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http://dx.doi.org/10.1007/s12011-021-02807-xDOI Listing
June 2021

Surgical scar revision using silicone gel sheet as an adjunct.

Natl J Maxillofac Surg 2021 Jan-Apr;12(1):36-41. Epub 2021 Mar 16.

Department of Oral and Maxillofacial Surgery, Himachal Institute of Dental Sciences, Sirmaur, Himachal Pradesh, India.

Introduction: Scar is often referred to as an unattractive mark after healing of a wound. An undesirable scar may have negative social, emotional, and functional impact on the patient. It is our job as surgeons to adequately understand the expectations of the patient and counsel them for a successful procedure.

Materials And Methods: Twelve patients were randomly chosen for the study, of which five were males and seven were females. The scar tissue was removed surgically, and silicone gel sheets (SGSs) were applied on the 14 postoperative day, and the dimensions of the new scar was measured periodically up to 12 months.

Results: The study comprised of 12 patients- 5 males and 7 females. The descriptive statistics were calculated as median and interquartile range and comparison between time intervals was done using Wilcoxon signed rank test. Out of the 12 patients, 10 showing complete resolution of the scar and 2 patients had partial relapse of scar. However, they were satisfied with the final outcome.

Conclusion: Our study found that SGSs applied to surgically revised scars significantly improves their appearance. The ease of use of the SGSs also makes it patient friendly. We observed almost complete resolution of the scar in ten patients and two patients exhibited partial relapse of the scar. However, there was a significant improvement in the overall appearance of the scar, and the patients were satisfied with the results of the procedure.
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http://dx.doi.org/10.4103/njms.NJMS_106_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191553PMC
March 2021

Epidemiology of overweight and obesity in Indian adults - A secondary data analysis of the National Family Health Surveys.

Diabetes Metab Syndr 2021 Jul-Aug;15(4):102166. Epub 2021 Jun 11.

Department of Endocrinology, Bharti Hospital, Karnal, Haryana, India. Electronic address:

Aims: National Family Health Survey (NFHS) conducted in India provide nationally comparable data on socio-demographic characteristics and anthropometric estimates. Present study was conducted to examine the prevalence of Indian adults who are living with overweight/obesity, their correlates, and trends observed between the last two rounds of the NFHS 2005-06 to 2015-16).

Methods: Socio-demographic characteristics and anthropometric estimates of respondents from NFHS round III & IV were analysed. Asian cut-offs were used for obesity classification. Of the total 198,754 and 811,808 eligible respondents, adults ≥18 years of age were included in the analysis. Prevalence and correlates were presented after taking into account stratification, clustering and sampling weights. GIS mapping was done to depict regional variations.

Results: Prevalence of men and women living with overweight/obesity were observed to be 38.4% and 36.2% respectively. Wide variations were observed in prevalence across the regions of India. Results of multivariate analysis showed that the strongest predictors for being overweight or obese were older age, currently in union, higher education, richest wealth quintile, and living in urban areas.

Conclusion: The present study highlights the rising prevalence across the urban and rural locations and has implications for policy change based on the prevalence estimates.
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http://dx.doi.org/10.1016/j.dsx.2021.06.003DOI Listing
June 2021

Strength and Comprehensiveness of Drinking Water Language in California School District Wellness Policies.

J Nutr Educ Behav 2021 Oct 22;53(10):870-879. Epub 2021 Jun 22.

School of Medicine, Stanford University, Stanford, CA; Philip R. Lee Institute for Health Policy Studies, University of California San Francisco, San Francisco, CA. Electronic address:

Objective(s): Assess the quality of water language in California school district wellness policies and examine how language quality relates to school drinking water access.

Design: Cross-sectional study.

Participants: Random sample of 240 schools selected from all California public schools, stratified by geography and grades served.

Variables Measured: Policies (2016-2018) were coded for quality (strength and comprehensiveness) using an adapted school wellness policy tool. School administrators completed phone interviews about drinking water access on their campus.

Analysis: Descriptive statistics (eg, means, standard deviations) summarized school-level characteristics and main outcomes. Mixed-effects linear regression models were used to examine the relationship between the strength and comprehensiveness of water policy language and water access.

Results: On a scale of 0-100, mean strength was 11.3 (SD, 5.7), and mean comprehensiveness was 28.8 (SD, 8.7). There was an inverse association between the quality of water language in policies and excellence in drinking water access in schools.

Conclusions And Implications: The strength and comprehensiveness of water language in California school district wellness policies were low. Districts would benefit from improving the quality of water language in their wellness policies and examining challenges to implementing policies.
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http://dx.doi.org/10.1016/j.jneb.2021.04.466DOI Listing
October 2021

Screening of potential bio-molecules from against SARS-CoV-2 main protease using computational approaches.

J Biomol Struct Dyn 2021 Jun 21:1-12. Epub 2021 Jun 21.

Department of Botany, Kumaun University, Nainital, Uttarakhand, India.

COVID-19 caused by SARS-CoV-2 is responsible for the deaths of millions of people worldwide. It is having devastating effects on the people of all countries. In this regard, the phytochemicals of medicinal plants could be explored to prevent this disease. is a miracle plant with antibacterial, antiviral, and antioxidant properties because of its high content of flavonoids, glucosides and glucosinolates. Therefore, we constructed a library of 294 phytochemicals of and filtered it through the FAF-Drugs4. Further, molecular docking studies of filtered phytochemicals were performed with Mpro enzyme to investigate the binding interactions. Drug likeness properties, ADMET prediction were analyzed to determine the therapeutic aspect of these compounds. Based on the binding energy score of the top 4 compounds, the results indicate that Vicenin-2 has the highest binding affinity (-8.6 kcal mol) as compared to the reference molecule (-8.4 kcal mol). ADMET result reveals that all top four compounds have minimal toxic effects and good absorption. Further, 500 ns molecular dynamics simulation of the top four compounds showed that Kaempferol-3-O-rutinoside and Vitexin have good stability with Mpro. These two compounds were then subjected for MMPBSA (last 50 ns) calculation to analyze the protein-ligand stability and dynamic behavior. Kaempferol-3-O-rutinoside and Vitexin showed very good binding free energy i.e. -40.136 kJ mol and -26.784 kJ mol, respectively. Promising outcomes from MD simulations evidence the worth of these compounds for future drug development to combat coronavirus disease.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2021.1936183DOI Listing
June 2021

Distribution of Fluoride in Plasma, Brain, and Bones and Associated Oxidative Damage After Induced Chronic Fluorosis in Wistar Rats.

Biol Trace Elem Res 2021 Jun 14. Epub 2021 Jun 14.

Division of Veterinary Animal Nutrition, Faculty of Veterinary Sciences and Animal Husbandry, SKUAST-J, Ranbir Singh Pura, 181102, Jammu and Kashmir, India.

The study was aimed to determine fluoride levels in plasma, brain, and bones of Wistar rats following chronic administration of fluoride at different dose levels and the consequent oxidative damage inflicted in these tissues. Brain histomorphology and bone radiographs were also evaluated to assess the extent of damage in these organs. Eighteen rats were randomly divided into three groups with six animals in each group. Group I served as control and groups II and III received 50 and 100 ppm fluoride in tap water, respectively for 180 days. A dose-dependent rise in the levels of fluoride in plasma, brain, and bones was observed in rats. Significant (P < 0.05) alterations in levels of total thiols, glutathione peroxidase, glutathione reductase, acetylcholinesterase, catalase, superoxide dismutase, lipids, as well as protein peroxidation in blood and brain were observed as compared to control in a dose-dependent manner. Radiological examination of bone revealed thinning of bone cortex with haphazard ossification, reduced bone density, and widening of marrow cavity indicating occurrence of flawed bone remodeling upon chronic fluoride exposure. Improper mineralization in bones of intoxicated rats indirectly reflected reduced bone tensile strength. Moreover, alterations in plasma Ca:P ratio and high levels of fluoride in bone ash indicated that chronic fluoride exposure leads to alterations in the bone matrix further corroborating the radio-graphical findings. Additionally, severe microscopic alterations were recorded in the cerebrum and cerebellum of treated rats which included neuronal necrosis, gliosis, spongiosis, perivascular cuffing, congestion, and hemorrhage which correlated well with oxidative changes induced by fluoride intoxication in the brain tissue of rats.
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http://dx.doi.org/10.1007/s12011-021-02782-3DOI Listing
June 2021

Antimicrobial activity of methanolic extracts of Vernonia cinerea against Xanthomonas oryzae and identification of their compounds using in silico techniques.

PLoS One 2021 14;16(6):e0252759. Epub 2021 Jun 14.

Computational Biology & Biotechnology Laboratory, Department of Botany, Soban Singh Jeena University, Almora, Uttarakhand, India.

Bacterial Leaf Blight (BLB) disease is an extremely ruinous disease in rice, caused by Xanthomonas oryzae pv. oryzae (Xoo). Although various chemicals are available to manage BLB, they are toxic to the environment as well as humans. Hence there is a need to develop new pesticides as alternatives to hazardous chemicals. Therefore, a study was carried out to discover new potent natural pesticides against Xoo from different solvent extracts of Vernonia cinerea. Among all the fractions, the methanolic extract showed the highest inhibition zone. Further, to gain mechanistic insight of inhibitory action, 40 molecules of methanolic extracts were subjected for in silico study against two enzymes D-alanine-D-alanine ligase (Ddl) and Peptide deformylase (PDF). In silico study showed Rutin and Methanone, [1,4-dimethyl-7-(1- methylethyl)-2- azulenyl]phenyl have a good binding affinity with Ddl while Phenol, 2,4-bis(1-phenylethyl)- and 1,2-Benzenedicarboxylic acid, diisooctyl ester showed an excellent binding affinity to PDF. Finally, the system biology approach was applied to understand the agrochemical's effect in the cell system of bacteria against both the enzymes. Conclusively, these four-hit compounds may have strong potential against Xoo and can be used as biopesticides in the future.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252759PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202908PMC
June 2021

The predictive ability of the 313 variant-based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant.

Genet Med 2021 09 10;23(9):1726-1737. Epub 2021 Jun 10.

Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.

Purpose: To evaluate the association between a previously published 313 variant-based breast cancer (BC) polygenic risk score (PRS) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes.

Methods: We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS and CBC risk.

Results: For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06-1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS, HR = 1.15, 95% CI (1.07-1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC < age 40 years, the cumulative PRS 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively.

Conclusion: The PRS can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the PRS needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decision-making.
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http://dx.doi.org/10.1038/s41436-021-01198-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460445PMC
September 2021

Development and validation of a rapid high-performance thin-layer chromatographic method for quantification of gallic acid, cinnamic acid, piperine, eugenol, and glycyrrhizin in Divya-Swasari-Vati, an ayurvedic medicine for respiratory ailments.

J Sep Sci 2021 Aug 23;44(16):3146-3157. Epub 2021 Jun 23.

Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, India.

Divya-Swasari-Vati is a calcium containing polyherbal ayurvedic medicine prescribed for the lung-related ailments observed in the current pandemic of Severe Acute Respiratory Syndrome Coronavirus 2 infections. The formulation is a unique quintessential blend of nine herbs cited in Ayurvedic texts for chronic cough and lung infection. Analytical standardization of herbal medicines is the pressing need of the hour to ascertain the quality compliance. This persuaded us to develop a simple, rapid, and selective high-performance thin-layer chromatographic method for Divya-Swasari-Vati quality standardization. The developed method was validated for the quantification of marker components, gallic acid, cinnamic acid, piperine, eugenol and glycyrrhizin, against reference standards in five different batches of Divya-Swasari-Vati. The analytes were identified by visualization at 254 nm, and by matching their retention factor with authentic standards. The developed method was validated as per the guidelines recommended by the International Council for Harmonization for parameters like, linearity, limit of detection, limit of quantification, accuracy, and precision. Therefore, the developed novel high-performance thin-layer chromatographic process could be employed for rapid standardization of Divya-Swasari-Vati and other related herbal formulation, which would aid in quality manufacturing and product development.
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http://dx.doi.org/10.1002/jssc.202100096DOI Listing
August 2021

Intra-dural intercommunications between dorsal roots of adjacent spinal nerves and their clinical significance.

Surg Radiol Anat 2021 Sep 7;43(9):1519-1526. Epub 2021 May 7.

Department of Anatomy, Smt. B. K. Shah Medical Institute and Research Centre, Sumandeep Vidyapeeth, Piparia, Vadodara, 391760, Gujarat, India.

Purpose: The dorsal roots of adjacent spinal nerves are known to communicate with each other through rami communicantes. These intercommunications can cause deviations in the normal dermatomal organization which leads to errors during clinical decision-making. The objective of the study was to augment the existing knowledge of these communications which shall help minimize the diagnostic and therapeutic errors.

Methods: The present study examined thirty cadaveric spinal cord specimens to document the data of intra-dural, intercommunications between dorsal roots of adjacent spinal nerves.

Results: All the regions of the spinal cord exhibited the presence of intercommunications with variable frequency. The intercommunications were categorized into a total of nine groups based on their patterns. The levels of spinal cord exhibiting higher and lower frequencies of intercommunications were identified.

Conclusion: This information will be useful during the clinical evaluation of patients with spinal cord pathologies or radiculopathies. The outcomes of rhizotomy can also be improved with knowledge of intercommunications.
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http://dx.doi.org/10.1007/s00276-021-02761-2DOI Listing
September 2021

Oxidative Stress, Neuroinflammation, and NADPH Oxidase: Implications in the Pathogenesis and Treatment of Alzheimer's Disease.

Oxid Med Cell Longev 2021 16;2021:7086512. Epub 2021 Apr 16.

Department of Biochemistry, MM Institute of Medical Sciences & Research, Maharishi Markandeshwar Deemed University, Mullana, Ambala, Haryana, India.

NADPH oxidase as an important source of intracellular reactive oxygen species (ROS) has gained enormous importance over the years, and the detailed structures of all the isoenzymes of the NADPH oxidase family and their regulation have been well explored. The enzyme has been implicated in a variety of diseases including neurodegenerative diseases. The present brief review examines the body of evidence that links NADPH oxidase with the genesis and progression of Alzheimer's disease (AD). In short, evidence suggests that microglial activation and inflammatory response in the AD brain is associated with increased production of ROS by microglial NADPH oxidase. Along with other inflammatory mediators, ROS take part in neuronal degeneration and enhance the microglial activation process. The review also evaluates the current state of NADPH oxidase inhibitors as potential disease-modifying agents for AD.
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http://dx.doi.org/10.1155/2021/7086512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068554PMC
May 2021

Small Extracellular Vesicles in Pre-Therapy Plasma Predict Clinical Outcome in Non-Small-Cell Lung Cancer Patients.

Cancers (Basel) 2021 Apr 23;13(9). Epub 2021 Apr 23.

Department of Medical Oncology, University General Hospital of Larissa, 41334 Larissa, Greece.

The potential use of plasma-derived small extracellular vesicles (sEV) as predictors of response to therapy and clinical outcome in chemotherapy-naïve patients with non-small-cell lung cancer (NSCLC) was explored. sEV were isolated by size-exclusion chromatography from the plasma of 79 chemotherapy-naïve NSCLC patients and 12 healthy donors (HD). sEV were characterized with regard to protein content, particle size, counts by qNano, morphology by transmission electron microscopy, and molecular profiles by Western blots. PD-1 and PD-L1 expression on circulating immune cells was analysed by flow cytometry. Pre-treatment levels of total sEV protein (TEP) were correlated with overall (OS) and progression-free survival (PFS). The sEV numbers and protein levels were significantly elevated in the plasma of NSCLC patients compared to HD ( = 0.009 and 0.0001, respectively). Baseline TEP levels were higher in patients who developed progressive disease compared to patients with stable disease ( = 0.007 and 0.001, stage III and IV, respectively). Patient-derived sEV were enriched in immunosuppressive proteins as compared to proteins carried by sEV from HD. TEP levels were positively correlated with CD8PD-1 and CD8PD-L1 circulating T cell percentages and were independently associated with poorer PFS ( < 0.00001) and OS ( < 0.00001). Pre-therapy sEV could be useful as non-invasive biomarkers of response to therapy and clinical outcome in NSCLC.
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http://dx.doi.org/10.3390/cancers13092041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122966PMC
April 2021

AMR-Diag: Neural network based genotype-to-phenotype prediction of resistance towards β-lactams in and .

Comput Struct Biotechnol J 2021 29;19:1896-1906. Epub 2021 Mar 29.

Department of Biotechnology, Inland Norway University of Applied Sciences, Holsetgata 22, 2317 Hamar, Norway.

Antibiotic resistance poses a major threat to public health. More effective ways of the antibiotic prescription are needed to delay the spread of antibiotic resistance. Employment of sequencing technologies coupled with the use of trained neural network algorithms for genotype-to-phenotype prediction will reduce the time needed for antibiotic susceptibility profile identification from days to hours. In this work, we have sequenced and phenotypically characterized 171 clinical isolates of and  from Norway and India. Based on the data, we have created neural networks to predict susceptibility for ampicillin, 3rd generation cephalosporins and carbapenems. All networks were trained on unassembled data, enabling prediction within minutes after the sequencing information becomes available. Moreover, they can be used both on Illumina and MinION generated data and do not require high genome coverage for phenotype prediction. We cross-checked our networks with previously published algorithms for genotype-to-phenotype prediction and their corresponding datasets. Besides, we also created an ensemble of networks trained on different datasets, which improved the cross-dataset prediction compared to a single network. Additionally, we have used data from direct sequencing of spiked blood cultures and found that AMR-Diag networks, coupled with MinION sequencing, can predict bacterial species, resistome, and phenotype as fast as 1-8 h from the sequencing start. To our knowledge, this is the first study for genotype-to-phenotype prediction: (1) employing a neural network method; (2) using data from more than one sequencing platform; and (3) utilizing sequence data from spiked blood cultures.
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http://dx.doi.org/10.1016/j.csbj.2021.03.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060595PMC
March 2021

Structure-function of anticoagulant TIX-5, the inhibitor of factor Xa-mediated FV activation.

J Thromb Haemost 2021 07 1;19(7):1697-1708. Epub 2021 May 1.

Amsterdam UMC, University of Amsterdam, Center for Experimental and Molecular Medicine, Amsterdam Infection and Immunity Institute, Amsterdam, The Netherlands.

Background: The prothrombinase complex consists of factors Xa (FXa) and Va (FVa) on an anionic phospholipid surface and converts prothrombin into thrombin. Both coagulation factors require activation before complex assembly. We recently identified TIX-5, a unique anticoagulant tick protein that specifically inhibits FXa-mediated activation of FV. Because TIX-5 inhibited thrombin generation in blood plasma, it was concluded that FV activation by FXa contributes importantly to coagulation.

Objective: We aimed to unravel the structure-function relationships of TIX-5.

Method: We used a structure model generated based on homology with the allergen Der F7.

Results: Tick inhibitor of factor Xa toward FV was predicted to consist of a single rod formed by several beta sheets wrapped around a central C-terminal alpha helix. By mutagenesis we could show that two hydrophobic loops at one end of the rod mediate the phospholipid binding of TIX-5. On the other end of the rod an FV interaction region was identified on one side, whereas on the other side an EGK sequence was identified that could potentially form a pseudosubstrate of FXa. All three interaction sites were important for the anticoagulant properties of TIX-5 in a tissue factor-initiated thrombin generation assay as well as in the inhibition of FV activation by FXa in a purified system.

Conclusion: The structure-function properties of TIX-5 are in perfect agreement with a protein that inhibits the FXa-mediated activation on a phospholipid surface. The present elucidation of the mechanism of action of TIX-5 will aid in deciphering the processes involved in the initiation phase of blood coagulation.
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http://dx.doi.org/10.1111/jth.15329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360041PMC
July 2021

Enhanced anti-cancer activity of andrographis with oligomeric proanthocyanidins through activation of metabolic and ferroptosis pathways in colorectal cancer.

Sci Rep 2021 04 6;11(1):7548. Epub 2021 Apr 6.

Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA.

The high degree of morbidity and mortality in colorectal cancer (CRC) patients is largely due to the development of chemoresistance against conventional chemotherapeutic drugs. In view of the accumulating evidence that various dietary botanicals offer a safe, inexpensive and multi-targeted treatment option, herein, we hypothesized that a combination of Andrographis paniculata and Oligomeric Proanthocyanidins (OPCs) might interact together with regard to anti-tumorigenic activity in CRC. As a result, we demonstrated the enhanced anti-cancer activity between these two botanical extracts in terms of their ability to inhibit cancer cell growth, suppress colony formation and induce apoptosis. Furthermore, we validated these findings in subcutaneous xenograft model and in patient derived primary epithelial 3D organoids. Transcriptomic profiling identified involvement of metabolic pathways and ferroptosis-associated genes, including HMOX1, GCLC and GCLM, that may be responsible for the increased anti-tumorigenic activity by the two compounds. Collectively, our study provides novel evidence in support of the combinatorial use of andrographis and OPCs as a potential therapeutic option, perhaps as an adjunctive treatment to classical drugs, in patients with colorectal cancer.
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http://dx.doi.org/10.1038/s41598-021-87283-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024269PMC
April 2021

Rollout of COVID-19 Vaccination in India: A SWOT Analysis.

Disaster Med Public Health Prep 2021 Apr 6:1-4. Epub 2021 Apr 6.

Department of Community Medicine, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India.

Objective: This study aimed to identify the strengths, weaknesses, opportunities, and threats (SWOT) in the rollout of the COVID-19 vaccination campaign in India.

Methods: The internal and external attributes affecting the vaccination rollout identifed by reviewing the scientific literature, government guidelines, and press statements, along with media reports, were categorized into the SWOT matrix.

Results: The existing immunization program, indigenous vaccine production, setting up of the National Expert Group on Vaccine Administration for COVID-19, updated guidelines, and training followed by dry runs were identified as strengths. The weaknesses identified in the program were knowledge gap about vaccines, apprehensions, lack of temperature loggers and vaccine vial monitors, space contraints in health care set up, demand supply gap, and digital divide. The experience of conducting the general elections, intersectoral coordination forged during the pandemic response, Information Technology platform, and vaccine eagerness present opportunities to strengthen the program. The emergence of virus variants, commercial interests, laxity in COVID-19 appropriate behavior, and receding wave of the pandemic can pose significant threats to the implementation of the vaccination campaign.

Conclusion: The study identified factors that can aid designing effective measures and countermeasures for the COVID-19 vaccination rollout. This SWOT analysis is relevant to low- and middle-income countries planning to implement the COVID-19 vaccination in the near future.
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http://dx.doi.org/10.1017/dmp.2021.111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193205PMC
April 2021

Comprehensive and Rapid Quality Evaluation Method for the Ayurvedic Medicine Divya-Swasari-Vati Using Two Analytical Techniques: UPLC/QToF MS and HPLC-DAD.

Pharmaceuticals (Basel) 2021 Mar 27;14(4). Epub 2021 Mar 27.

Drug Discovery and Development Division, Patanjali Research Institute, Haridwar 249 405, Uttarakhand, India.

Divya-Swasari-Vati (DSV) is a calcium-containing herbal medicine formulated for the symptomatic control of respiratory illnesses observed in the current COVID-19 pandemic. DSV is an Ayurvedic medicine used for the treatment of chronic cough and inflammation. The formulation has shown its pharmacological effects against SARS-CoV-2 induced inflammation in the humanized zebrafish model. The present inventive research aimed to establish comprehensive quality parameters of the DSV formulation using validated chromatographic analytical tools. Exhaustive identification of signature marker compounds present in the plant ingredients was carried out using ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/QToF MS). This was followed by simultaneous estimation of selected marker components using rapid and reliable high-performance liquid chromatography (HPLC) analysis. Eleven marker components, namely gallic acid, protocatechuic acid, methyl gallate, ellagic acid, coumarin, cinnamic acid, glycyrrhizin, eugenol, 6-gingerol, piperine and glabridin, were selected out of seventy-four identified makers for the quantitative analysis in DSV formulation. Validation of the HPLC method was evaluated by its linearity, precision, and accuracy tests as per the International Council of Harmonization (ICH) guidelines. Calibration curves for the eleven marker compounds showed good linear regression ( > 0.999). The relative standard deviation (RSD) value of intraday and interday precision tests were within the prescribed limits. The accuracy test results ranged from 92.75% to 100.13%. Thus, the present inclusive approach is first of its kind employing multi-chromatographic platforms for identification and quantification of the marker components in DSV, which could be applied for routine standardization of DSV and other related formulations.
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http://dx.doi.org/10.3390/ph14040297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067215PMC
March 2021

Anaesthesia management for Winchester syndrome.

Indian J Anaesth 2021 Feb 10;65(2):165-167. Epub 2021 Feb 10.

Department of Anaesthesia and Critical Care, Level III IFH Hospital, Goma, Democratic Republic of the Congo.

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http://dx.doi.org/10.4103/ija.IJA_984_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983827PMC
February 2021
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