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   Table of Contents - Current issue
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January-March 2022
Volume 6 | Issue 1
Page Nos. 1-158

Online since Friday, March 11, 2022

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REVIEW ARTICLES  

Safety and sagacious use of remdesivir: Paramount focus on contemporary perspectives Highly accessed article p. 1
Jeetendra Kumar Gupta
DOI:10.4103/bbrj.bbrj_161_21  
The outbreak of COVID-19 has severely impacted the viability on the earth. Its pathogen severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus has manifested catastrophic effect on the world's demographics and emerged as the most epizootic agent for human beings. Even though considerable progress in research has led to a better understanding of the virus, there is no specific and potent treatment or cure has been proven effective for this disease. Based on the available scientific evidences, U. S. Food and Drug Administration has issued an emergency use authorization for the emergency use of remdesivir against SARS-CoV-2 virus in critical and hospitalized patients. Remdesivir is a prodrug form of a nucleoside analog GS-441524. It is given intravenously because of its poor absorption through oral route. Remdesivir acts against viral RNA-dependent RNA polymerase targeting viral genome replication. It has been used in many countries as an emergency drug for the treatment of COVID-19 in hospitalized patients. However, in order to substantiate the result through suitable statistics, large-scale clinical trials are required. As per existing studies, the most common adverse effects reported after intravenous administration of remdesivir are elevation in the level of aminotransferase enzymes and bilirubin. Renal impairment, hypotension, and diarrhea have also been revealed in few patients. As of now, there is limited trial data available on remdesivir, so irrevocable epilogues cannot be drawn. However, it is believed by many therapists that irrational use of remdesivir should be prohibited. The erroneous use of remdesivir can lead to the SARS-CoV-2 virus mutating, and its consequence may be ill-starred in future.
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Common respiratory viruses and collapsing health: Prodigious focus on ambient air pollution p. 7
Jeetendra Kumar Gupta
DOI:10.4103/bbrj.bbrj_201_21  
Ambient air pollution is one of the treacherous and malign problems facing humanity and other living beings on the earth today. Although the air pollutants such as particulate matters (PM) and microscopic contaminants have been associated with widespread morbidity and mortality, studies have also indicated those pollutants as a potential synergist to respiratory infirmities in both adults and children. Many viral contaminants have also been reported as potential detriments of respiratory distresses. Exposure to poor grades of ambient air can lead to numerous health consequences, such as adverse effects on the lung, heart, and other vital organs. In recent years, many studies infer that pollution along with viral contaminants impart substantial worldwide burden of diseases on human beings. Excessive air suspended pollutants such as micro or nanoparticulate matters bring down the life expectancy of human beings in many ways. Regardless of the passage of entry, fine and ultrafine PM that enter into systemic circulation affect vascular endothelial cells by producing local oxidative stress and have the capacity to cross biological barriers, thereby creating numerous deleterious effects on vital organs. Pollution-induced systemic inflammation is mediated by proinflammatory cytokines such as interleukin-6, interleukin-1 β, and tumor necrotic factor-α. These systemic inflammatory mediators are implicated in causing or exacerbating many complications in the human body. This article is an attempt to accentuate the pollution-linked health impediments, as well as the fountainheads of ambient air pollution so that some effective strategies can be developed to manage this global peril.
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A review of literature on the pharmacogenomics of single-nucleotide polymorphisms Highly accessed article p. 14
Iffath Ahmed, Hamdan Iftikhar Siddiqui, Ghania Shehzad Qureshi, Grisilda Vidya Bernhardt
DOI:10.4103/bbrj.bbrj_245_21  
Pharmacogenomics is the study of how our genetic structure determines the response to a therapeutic intervention. It is a rapidly growing field that aims to elaborate the genetic basis for differences in drug response between different individuals and to use such genetic information to predict the safety, toxicity, and/or efficacy of drugs in individual patients or groups of patients. Although drug–drug interactions and environmental factors significantly contribute to interindividual variability in drug response, genetic factors (e.g., inherited variability of drug targets, drug-metabolizing enzymes, and/or drug transporters) also appear to have a major impact on drug response and disposition. When a gene variant is associated with a particular drug response in a patient, there is the potential for making clinical decisions based on genetics by adjusting the dosage or choosing a different drug. Single-nucleotide polymorphisms (SNPs), also called SNPs, are the most common type of genetic variation among people. They are basically a substitution of a single nucleotide that occurs at a specific position in the genome. They occur normally throughout a person's DNA. They occur almost once in every 1000 nucleotides on average, which means there are roughly 4–5 million SNPs in a person's genome. Most SNPs have no effect on health or development. Some of them, however, have proven to be very important in the study of human health, especially in the field of pharmacogenomics. Researchers have found SNPs that may help predict an individual's response to certain drugs, susceptibility to environmental factors such as toxins, and risk of developing particular diseases. Scientists assess gene variants affecting an individual's drug response the same way they assess gene variants associated with diseases: by identifying genetic loci associated with known drug responses, and then testing individuals whose response is unknown. SNPs account for the most common genetic differences from person to person and pharmacogenomics explores how such changes in genetic makeup effect drug responses, resistance, etc., With our literature review, we aim to study some of the effects of these SNPs on drug responses in patients. The purpose of the study was to understand and implicate the effects of SNPs in modern medicine and how it can be applied to personalize health care for every patient. A systematic literature search was carried in search of studies pertaining to personalized medicine and implications of SNPs. A thorough search through PubMed, Google Scholar, and ProQuest revealed 61 relevant studies. All study types were considered eligible. Over the past 10 years, tremendous progress has been made in cataloging human sequence variations since this high-density map can offer the required tools to develop genetically based diagnostic and therapeutic tests. When additional functional polymorphisms are known, it may be attainable to develop helpful genetic markers also as personalized medicines. In the future, the main aim is to use SNPs not only to find certain aspects to be used in the future (individualized drug therapy, development of genome-based diets, etc.) but to also unveil the details of genome evolution. A number of challenges exist today in realizing the value of a high-density map of anonymous SNPs for pharmacogenomics. Concerns about the high price of genotyping are being addressed; however, it may be several years before the price of genotyping large populations is acceptable. In addition, availability of large patient populations will be crucial for discovering and validating SNPs.
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Recent insights of SARS-CoV-2 potential inhibitors p. 21
Mohd Faheem, Vinay Kumar Singh, Abhishek Srivastava
DOI:10.4103/bbrj.bbrj_229_21  
The year of 2019–2021 is emergency that the world is facing due to the spread of 2019-nCoV which has created a very critical condition in human society, known as COVID-19. The complex virus belongs to the family of coronaviridae and genera betacoronavirus and spreads through human interaction. The common symptoms observed in infected are a sudden rise in body temperature within 1st to 9th day of infection, problems around the neck and throat from the start of the infection followed by the spread of infection into the lungs that cause novel coronavirus pneumonia and kidney failure. Many of the receptor proteins of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) and target proteins of the human cells are responsible for endocytosis such as main protease or 3C-like protease, RNA polymerase, and spike protein. These proteins play a vital role in the life cycle of SARS-CoV-2. Many of the computational designed drugs and docking-based drugs are reported as anti-COVID-19. Many of the drugs show strong potent activity against this deadly virus. This study demonstrates the synthetic and computational designed approach, drugs, and compounds for the potential inhibition of the SARS-CoV-2 virus. The review will be helpful in finding a new approach of a drug as an inhibitory receptor of SARS-CoV-2.
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Biomarkers of oral cancer: A current views and directions p. 33
Vidya Gowdappa Doddawad, Gurupadayya Bannimath, Shivananda Shivakumar, Namitha Bannimath
DOI:10.4103/bbrj.bbrj_204_21  
Tumor biomarkers are the chemical substances that the human body or cancer cells produce in response to the presence of cancer. These markers are mostly proteins that cancer cells produce more quickly. Patients with certain types of cancer have higher levels of these protein substances in their urine, blood, or body tissue and help differentiate between primary and secondary tumors. Oral carcinomas, especially of the head-and-neck region, represent a critical diagnostic challenge not only for the histopathologist but also for the clinician when planning an appropriate treatment protocol. For these reasons, the practice and understanding of these biomarkers have improved tremendously. This review not only sheds light on the different types of tumor markers but also shows their role in some diseases.
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Radiobioconjugate targeted therapy in cancer, using radiolabeled mediated biological analogs: Desired qualities and selective targeting approach p. 40
Pankaj Garg
DOI:10.4103/bbrj.bbrj_282_21  
Radiobioconjugate therapy, recommended as one of the effective modalities for the treatment of cancer cells, is based on the concept of delivering the localized radiation at the cellular level to the disease site using a biological moiety. The high tumor/nontumor ratio is the essentially a sine qua non for the successful execution of targeted therapy which is highly desired. The central problem associated to radiobioconjugate therapy is the small fraction of a radiobioconjugate localized to the tumor, while the major fraction of it is delivered to the nontarget organs (reticuloendothelial system deposition). The current article focuses on the better perceptive of the factors of understanding, which includes the selection and expansion of sophisticated molecular carriers, assortment of a suitable radionuclide based on the class of emission, linear energy transmit, and the material radiophysical half-life. In addition, a concern to the biochemical interactions taking place at the molecular level, selection of a specific targeting strategy for designing effective treatment regimes, and importantly the challenges associated to it have also been discussed.
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A review on COVID-19 vaccinations p. 50
Ketan Garg, Dipesh Talwar, Samiksha Naresh Mahajan, Sana Karim, Kesar Prajapati, Savan Patel, Bhawna Garg
DOI:10.4103/bbrj.bbrj_280_21  
The year 2019 witnessed a pandemic named COVID-19 caused by infection severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It emerged in Wuhan, China, in December 2019 and has affected millions since then. It led to a global cry for vaccine development. Scientists arrayed the SARS-CoV-2 genome within a month of the outbreak. They used the parallels between SARS-CoV-1 and SARS-CoV-2 to speed up the vaccine preparation. As of now, different types of COVID-19 vaccines are prevailing.
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ORIGINAL ARTICLES Top

Structural characterization of inclusion complex of stigmasterol with alpha-cyclodextrin using spectroscopy and molecular modeling p. 54
Kuruz Francy, Johnson Prema Kumari, Simon Lizy Roselet
DOI:10.4103/bbrj.bbrj_228_21  
Background: Stigmasterol possesses numerous physiological effects and is used as food supplements and behaves as a pharmaceutical agent. It exhibits anticancer effects against various cancers. The usefulness of the stigmasterol is restricted due to its poor solubility. To overcome this and enhance the solubility and bioavailability of this phytosterol, molecular encapsulation is utilized to augment the desirable properties of stigmasterol. This research work aims to investigate the interaction between stigmasterol and alpha-cyclodextrin (α-CD) in aqueous solution as well as in solid state and experimentally examined by spectral techniques. Methods: The liquid complexes are characterized by ultraviolet (UV)-visible spectroscopy and solid inclusion complexes are characterized by Fourier transformer infrared resonance and 1H nuclear magnetic resonance spectroscopy. The thermal behavior of the complex is analyzed by differential scanning calorimeter. Phase solubility studies are done to learn the solubility of the newly synthesized complex. Results: Formation constant from UV-visible analysis is found to be 569 M−1 by Benesi–Hildebrand equation. The solubility constant is calculated to be 52 M−1. The results obtained prove the inclusion which is confirmed through molecular docking studies. Conclusion: The newly synthesized inclusion complex is a potent pharmaceutical agent in drug formulation as stigmasterol solubility is enhanced when included in the cavity of α-CD.
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Scutellarein apoptosis mediated by mitochondria in oral squamous cell carcinomas p. 60
Markandan Birundadevi, Rangasamy Sivashankar, Sivagnanam Mathukumar
DOI:10.4103/bbrj.bbrj_251_21  
Background: The growth of several cancers can be inhibited by naturally occurring medicinal plants. A flavone called Scutellarein found in the perennial herb Scutellaria lateriflora does have a wide range of biological functions. Scutellarein was studied to determine whether it could induce apoptosis and cause cytotoxicity. Methods: On oral squamous cell carcinoma KB cell lines, Scutellarein's cytotoxic activity was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Scutellarein was added to KB cells at concentrations ranging from 25 to 125 g/mL for 24 h. The real-time polymerase chain reaction was also used to investigate apoptotic induction potential in Scutellarein-incubated KB cell lines by analyzing Bcl-2 protein and gene expression. Results: In KB-cell lines treated with scutellarein, cytotoxicity and anticancer effects were observed, as well as inhibit the growth of cancer cells. In comparison to the cells not treated with scutellarein, KB cells that had been exposed to scutellarein displayed reduced Bcl-2 expression. Conclusion: KB cells were treated with scutellarein to induce apoptosis, suggesting its potential as a chemo preventative agent. This activity appears to be mediated through the modulation of Bcl-2, a cytotoxic gene.
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Evaluation of antibacterial potential of Syzygium cumini against methicillin-resistant Staphylococcus aureus and macrolide-lincosamide-streptogramin B strains of Staphylococcus aureus and its liquid chromatography mass spectroscopy analysis p. 66
Amrullah Shidiki, Ashish Vyas
DOI:10.4103/bbrj.bbrj_139_21  
Background: The resistant strains of Staphylococcus aureus as in form of methicillin-resistant S. aureus (MRSA), inducible clindamycin resistant S. aureus (iMLSB) and constitutive clindamycin-resistant S. aureus (cMLSB) are the major causes of death. An ethnobotanical survey of Syzygium cumini revealed that bioactive compounds showed effective against tested these resistant strains of S. aureus. Methods: The main goal of this study is to screening of phytochemicals by different biochemical tests, antimicrobial evaluation as per agar well-diffusion method and identification of chemical constituents of leaves of Syzygium cumini via liquid chromatography mass spectroscopy (LCMS) technique. Results: The extractive yield was higher with ethanol extract (18.10 ± 0.10). Four phytoconstituents, alkaloids, flavonoids, terpenoids, and tannin found in four solvent extracts except hexane. The zone of inhibition was higher in aqueous extract with ranges 17–27 mm. Twenty different chemical constituents of leaves of aqueous extract of Syzygium cumini were identified through the application of LCMS data. Conclusion: The Syzygium cumini of phytoconstituents showed antibacterial activity against MRSA, iMLSB, and cMLSB. Thus, it may help for the treatment of diseases caused by MRSA, iMLSB, and cMLSB.
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Enhanced antifungal activity of Piper betle against candidiasis infection causing Candida Albicans and In silico analysis with its virulent protein p. 73
Ganesh Kumar Selvaraj, Jayaraj John Wilson, Nalini Kanagaraj, Eswarapandian Subashini, Sivakumar Thangavel
DOI:10.4103/bbrj.bbrj_154_21  
Background: The widespread usage of synthetic chemical drugs often contributes to the development of drug resistance in the clinical pathogens along with hazardous side effects in the human side. Among those clinical pathogens, Candida albicans is a prime consideration to explore. C. albicans is wildly causing a fungal infection of oral cavity well known as candidiasis. This study is prompted to find some novel natural compounds from a medicinal plant, Piper betle against C. albicans. Methods: Bioactive compounds were extracted from the betel leaves using different solvents. The standard drug, fluconazole was used to check anticandidal activity of P. betle against C. albicans. Plant extracts were further characterized by the antioxidant and different scavenging assays. The biocompounds were identified using gas chromatography–mass spectrometry and successfully subjected to molecular docking study. Results: Methanol and ethanol extracts were showed potential antifungal, antioxidant, and scavenging activity against C. albicans, in comparison with control drug. Twenty-seven bioactive compounds were identified in the methanol extract of P. betle. These active bioactive compounds were docked with candidapepsin-1, a proteolytic virulent enzyme of C. albicans and compared with a control drug, fluconazole (−7.8 kcal/mol), and the effective interaction was observed with specific bioactive compound, 4-hydroxy-5-imino-3,4-dimethyl-1-(4-nitrophenyl)-2-imidazolidinone (−7.5 kcal/mol). Conclusion: The present study reveals that methanol and ethanol extract of P. betle is a potential source of natural-free radical scavenging antioxidants. These findings will be great helpful in the new drug analysis for the determination of antimicrobial biocompounds against candidiasis and other clinically related infections.
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Sickle cell disease: Assessment of hemostasis parameters in steady-state patients at Tertiary Care Hospital, Indore, India p. 81
Gajendra Kumar Gupta, Purnima Dey Sarkar, Rohit Manyal, Mithun Singh Rajput
DOI:10.4103/bbrj.bbrj_162_21  
Background: The evidence from various studies showed that patients with sickle cell disease (SCD) have altered components of hemostasis such as platelet function, procoagulant, anticoagulant and fibrinolytic pathways, and modulate inflammation such as acute or chronic inflammatory state. These components may alter based on race, regions, or environment. Assessment of the hemostatic parameters in our region is imperative because the altered components so involved may give an insight as to the clinical phenotypes of Arab-Indian haplotypes we have in our setting. The objective of present study is to assess basic hemostatic and inflammatory parameters in patients with SCD during steady state at a tertiary care hospital. Methods: Blood samples of 95 patients with SCD during steady state attending M. Y. Hospital, Indore, India, during the period of November 2019 to March 2020 were screened for C-reactive protein (CRP) levels and platelet counts using latex enhanced immune-turbidimetric assay and hemotology analyzer, respectively, while prothrombin time (PT) and activated partial thromboplastin time (APTT) by automated coagulation analyzer. Results: It was observed that there is no significant difference among the mean platelet count (321.9 ± 97.63 × 109/l) of SCD patients and control groups (P = 0.69). CRP levels (6.60 ± 2.83 mg/l) were found to be significantly increased (P < 0.01) in SCD patients in comparison with their respective control. The mean PT (15.21 ± 1.58 s) and APTT values (37.69 ± 2.50 s) were found to be significantly increased (P < 0.05 for both) in SCD patient group when compared with control group. Conclusion: The study confirms that patients with SCD in steady state have significant prolonged coagulation indices. These can be an evidence of hypercoagulable state in SCD and may provide reference values appropriate for therapeutic target. We recommend that patients of SCD especially those with severe vaso-occlusive crises should have these hemostatic parameters as a basic test and during routine clinic follow-up for improved management.
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Knowledge, attitude, and practices of renal diets among hemodialysis patients p. 86
Saumiya Kanagarajah, Supriya Velraja, Hemamalini Janardhanan Arambakkam
DOI:10.4103/bbrj.bbrj_200_21  
Background: Malnutrition and mineral disparities has become increasingly common in patients with the end-stage renal disease treated with hemodialysis (HD). Lack of nutritional knowledge is one of the most significant reasons for nutritional problems leading to improper practice and causing several complications. The objectives of the study were to asses the nutrition knowledge, attitude, and practice of HD patients regarding renal diet, to counsel the patients on HD dietary guidelines and to determine the association of factors such as income and education level on nutrition management of HD Patients. To assess the nutrition knowledge, attitude, and practice of HD patients regarding renal diet. To counsel the patients on HD dietary guidelines. To determine the association of factors such as income and education level on nutrition management of HD patients. Methods: A total of 120 patients undergoing HD were assessed for the level of nutrition knowledge, attitude, and practice, regarding HD dietary guidelines, using a validated questionnaire. Results: About 60.3% of HD patients had excellent knowledge, 60% had excellent attitude, and 40% had excellent practices. There is a significant positive correlation between knowledge and attitude, as well as knowledge and practice (r < 0.01) of the patients undergoing HD regarding renal diet. There is also a significant association between the knowledge, attitude, and practice scores with the selected demographical variables (education level and income) of patients at the significance level of P < 0.001. Conclusion: Although majority of the patients have excellent knowledge, attitude, and practice, a notable number of patients are unaware about their dietary guidelines and do not adhere to the dietary regime that needs to be followed. Diet counseling by a renal dietitian using a nutrition education module can effectively upgrade the nutrition knowledge, attitude, and practice of HD dietary guidelines by the patients.
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In silico approach for the identification of mirror repeats in selected operon genes of Escherichia coli strain K-12 substrain MG1655 p. 93
Sandeep Yadav, Usha Yadav, Dinesh Chandra Sharma
DOI:10.4103/bbrj.bbrj_146_21  
Background: The repeating elements in the genes or genomes of living organisms are associated with a variety of functions at the molecular level. Mirror repeats (MRs) are unique type of repeat sequences among them, which are found to be linked with H-DNA formation and they have also associated with several neurological disorders with many other functional roles are also being reported. Methods: The manual bioinformatics-based approach is used to identify the MRs in the genome. The applied approach FASTA-parallel complement-BLAST is used by following some simple steps to identify MRs. This methodology is initiated by the downloading of a sequence of interest in FASTA format followed by development of the parallel complement and final step of BLAST analysis. By using this approach, the present study identifies MRs in lac, trp, and ara operon genes of Escherichia coli str. K-12 substr. MG1655 (NC_000913.3). Results: Present investigation identified the frequent distribution MRs in all the analyzed operon genes. These identified MRs vary in their length or size. In case of lac, trp, and ara operon, maximum number of MRs reported in lacZ (61), trpE (40), and araE (41) genes, respectively. Conclusion: The frequent existence of MRs (shorter as well as larger length) in analyzed genes gives a hint about their significant roles in the genes or genomes of all bacterial species. These may be useful to study the evolutionary history of living world. These types of studies will be exploring new trends and tools of molecular biology research as well as development of new concept for MR identification.
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Antibacterial and antibiofilm properties of Azadirachta indica (Neem), Aloe vera (Aloe vera), and Mentha piperita (Peppermint) against multidrug-resistant clinical isolates p. 98
Priya Mehrishi, Priti Agarwal, Shobha Broor, Amisha Sharma
DOI:10.4103/bbrj.bbrj_178_21  
Background: Misuse of antibiotics globally has resulted in the development of resistant bacterial strains. One of the sole reasons for bacteria being resistant to antibiotics is the production of biofilm. Biofilms are microbial communities which get adhere to solid surfaces easily and pose an important virulence factor for causing many chronic infections. Therefore, there is an urge to find out new potential sources which can be used as an alternative to the existing antibiotics. Methods: The present study was conducted on three medicinal plant extracts Azadirachta indica, Aloe vera, and Mentha piperita to assess their antibacterial and antibiofilm properties against 58 multidrug-resistant clinical isolates using agar well diffusion method, minimum bactericidal concentration (MBC), and crystal violet modified assay at 50, 25, 12.5, and 6.25 mg/ml concentration. Results: A. indica showed a maximum zone of inhibition of (17.8 ± 1.52 mm) and (18.1 ± 1.45 mm) at 50 and 25 mg/ml concentration. Biofilm inhibition was more than 80% for Staphylococcus aureus and Pseudomonas aeruginosa and MBC came out to be 6.25 ± 2.96–6.25 ± 4.91 mg/ml (mean range). A. vera showed the highest zone of inhibition for S. aureus (18.2 ± 1.48 mm) at 50 mg/ml concentration followed by Staphylococcus saprophyticus (17.8 ± 1.48 mm) and Staphylococcus epidermidis (18.0 ± 1.60 mm). Biofilm inhibition was seen more than 50% and MBC was 50 ± 23.14–50 ± 25.72 mg/ml (mean range). Conclusion: All the three plant extracts were effective, but A. indica and A. vera were found to be more potent than M. piperita.
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Antioxidant-rich peridialytic granola bar for hemodialytic subjects p. 105
Sudhishna Kumar, Supriya Velraja, Hemamalini Janardhanan Arambakkam
DOI:10.4103/bbrj.bbrj_235_21  
Background: Chronic kidney disease is an emerging major noncommunicable health problem globally. The hemodialysis procedure results with increase in lipid peroxidation and decrease in antioxidant enzymes such as superoxide dismutase with change in serum antioxidant activity. The aim of the study is to formulate an antioxidant-rich peridialytic granola bar to supplement hemodialysis patients. Methods: The recipe was formulated using oats, ground nuts, dehydrated papaya, flax seeds, almonds, honey, and vegetable oil. To make the supplement antioxidant-rich, dehydrated papaya, honey, and vegetable oil have been selected. Results: The amount of antioxidant in the analyzed peridialytic granola bar has been compared with the recommended dietary allowance (RDA) for the hemodialysis patients and the quantity for supplementation has been finalized. The 80 g of peridialytic granola bar provides around 3369.6 μg of antioxidant, 15 g of protein, and 346.4 kcal of energy to meet the two-third of the recommended antioxidants and one-fourth of the protein and energy. Conclusion: The composition of the developed bar was standardized through organoleptic evaluation. The antioxidant content of the developed product was analyzed and compared with RDA. Eighty grams, i.e., 2 numbers of peridialytic granola bar, will provide roughly around 3369.6 μg of antioxidant, 15 g of protein, and 346.4 kcal of energy. This nutritional value is equivalent to approximately 1 serving of standard commercial formulas of 50 g. The formulated antioxidant-rich peridialytic granola bar can be considered for supplementation for 4 weeks to the subjects undergoing hemodialysis to reduce their oxidative stress.
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Assessment of the sofosbuvir + daclatasvir (±) ribavirin treatment and the prognostic efficacy of interferon-gamma induced protein 10, macrophage inflammatory-1-beta, and C-reactive protein in Hepatitis C Egyptian patients' therapy outcome p. 109
Hany Mohammed Ibrahim, Faten Roshdy Abdel-Ghaffar, Ahmed Bahgat Zied, Sameha Husni El-Ghareeb
DOI:10.4103/bbrj.bbrj_209_21  
Background: Hepatitis C virus (HCV) is the most important virus among the infectious agents as the cause of liver disease in Egypt. The aim of this work was to assess the efficacy and tolerability of the sofosbuvir + daclatasvir (±) ribavirin (SOF + DCV [±] RBV) regimens and to evaluate the association of interferon-gamma induced protein 10 (IP-10) and macrophage inflammatory-1-beta (MIP-1β) and C-reactive protein (CRP) with treatment responses as potential biomarkers for the prognosis of HCV in patients from Kafer EL-Sheikh Province, Egypt. Methods: HCV Patients were treated with a combined treatment of SOF plus DCV with or without RBV for 12 weeks. The biochemical, hematological parameters, HCV RNA load, IP-10, MIP-1β, and CRP were detected pre- and post-treatment. Results: Both SOF-based regimens improved the liver function, anemia, leukopenia, and thrombocytopenia especially after treatment with SOF, DCV, and RBV. Sustained virological response 12 was slightly higher in the group receiving (SOF and DCV) therapy (99.42%) when compared to (SOF, DCV, and RBV) therapy (98.44%). The most common adverse events were fatigue, headache, anorexia, rash, and nausea. Interestingly, higher levels of the IP-10, MIP-1β, or CRP were observed in the serum of patients with HCV before treatment, and their levels significantly decreased after the treatment of both regimens. Conclusions: Our study revealed that SOF-based regimens are efficacious in controlling the HCV load and IP-10, MIP-1β, or CRP have both bioprognostic efficacy and potential role in predicting treatment responses.
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Histopathological characterization of carcinoma breast with BRCA1/2 sequence variation in a Tertiary Care Center in Kerala, South India p. 117
Reeba Mary Issac, Prema Saldanha, Jessy Mangalathu Mathai, Jency Mathews, Rebecca Mathews, Bindu Kumari, Tiju Chacko
DOI:10.4103/bbrj.bbrj_206_21  
Background: Hereditary breast cancers constitute around 5%–10% of all breast cancers. The most commonly mutated genes in hereditary breast and ovarian cancer syndrome are the BRCA1 and BRCA2 genes. There has not been any research into the histopathological features of BRCA1/2 mutations in breast cancer in Kerala. The goal of this work was to use next-generation sequencing to look into the range of BRCA1/2 genetic variants and to discover characteristic histopathologic features associated with BRCA1/2 sequence variations. Methods: Fifty female patients diagnosed with carcinoma breast were screened for BRCA1/2 variants by next-generation sequencing. Patients were selected irrespective of age or family history of breast or ovarian cancer. The histopathological features of BRCA1/2 associated breast cancer cases were also studied. Results: We identified sequence variants in BRCA1 and BRCA2 genes in 6 women (6/50, 12%). The sequence variants included two deleterious mutations and five variants of uncertain significance. It was observed that most of the patients with BRCA1/2 sequence variants presented with aggressive tumor characteristics. Statistical significance was noted in BRCA1/2 carriers with tumors of higher histologic grade (P = 0.048). Conclusion: Morphological and immunohistochemical features of BRCA1/2-associated breast cancer may be valuable to predict mutation carrier status for appropriate therapeutic decision-making.
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Seroprevalence and risk factors for Hepatitis C virus among maintenance hemodialysis patients at a Tertiary Care Hospital in Puducherry, India p. 122
Latha Ragunathan, Kavitha Kannaiyan, Vithiavathi Subramanian, Marcella Sherin Samuel, Murugavel Mahendran
DOI:10.4103/bbrj.bbrj_240_21  
Background: Hepatitis C virus (HCV) infection is a serious public health problem and the most significant cause of liver disease in patient receiving dialysis for a long term. The prevalence of HCV infections among dialysis patients varies markedly from country to country. Tight infection control measures implemented in developed countries have minimized the transmission rate, while the prevalence still remains high in the developing world. The aim of this study is to estimate the prevalence rate of HCV infection in hemodialysis patients, to describe demographic characteristics of individuals infected with HCV and to determine whether HCV-polymerase chain reaction (PCR) testing identifies HCV infections not detected by anti-HCV testing. Methods: This retrospective record-based study was carried in Aarupadai Veedu Medical College and Hospital, a Tertiary Care Center in Puducherry, A total of 258 chronic renal failure patients on hemodialysis were studied and tested for anti-HCV antibodies by 4th generation HCV TRIDOT ELISA and real time-PCR. Results: Anti-HCV antibodies were positive in 34 (13.2%) patients, comprising 27 (79.4%) males and 7 (20.6%) females. The majority of patients were found to be positive; between 41 and 60 age 24 (70.5%). HCV RNA was detected in 38 (14.72%) patients. The mean age of patients undergoing dialysis was 45 years. 12 (35%) had raised aspartate transaminase (AST) levels and 14 (41%) had raised alanine transaminase (ALT) levels. Gamma-glutamyl transferase was found to be raised in 25 (73.5%) of the subjects. All the 34 HCV seropositive patients were hypertensive and 33% had diabetes mellitus. 23 (67.6%) patients had undergone dialysis in more than one center. Conclusions: Regular screening of patients for HCV is absolute necessity for early detection of HCV infection that could result in better management of patients and also stresses on the importance of HCV RNA detection by PCR. Strict adherence to universal precautions, the use of dedicated machines along with regular surveillance for HCV in HD units will dramatically decrease the risk of transmission of HCV.
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Association with oral microbial alteration and oral disease among patients attending ruhengeri referral hospital, Rwanda: A case–control study p. 126
Callixte Yadufashije, Joseph Mucumbitsi, Marie Jeanne Umugwaneza Uwimana, Liliane Muhimpundu, Lydia Nzisa Mwanzia, Martin Ndayambaje, Emmanuel Munyeshyaka, Gratien Twagirumukiza, Albert Onyango Mala
DOI:10.4103/bbrj.bbrj_271_21  
Background: Dental disease remains a public health concern of this era. In 2020, World Health Organization reported that 3.5 billion of oral disease occurs every year. About 2.3 billion case is attributed to dental caries while gum disease affects 10% of the global population. Methods: This was a case control study carried out from November 2020 to February 2021. About 120 participants were recruited, of them, 60 were oral diseased, while the remaining 60 were selected as a control group. Oral swab samples were collected with the swab stick, and put into plastic sterile container to avoid external microbial contamination. Samples were transported to INES clinical microbiology laboratory for microbial identification. chi square was performed to test for association, while odd ratios and relative risk were performed to test for pathogenic microbial fraction. Results: The common oral diseases were tooth decay (56.6%) and gum disease (43.4%). the most affected age range was 5-19years (53.33%), while females (63.3%) were the most affected sex. The most isolated microorganism was Lactobacillus spp (15.8%) for patients, while Staphylococcus aureus (11.2%) was the most isolate in the control group. The statistical significant association with oral microbial alteration and oral disease was observed on Streptococcus mutans (x2=8.9, P= 0.002852), Lactobacillus spp (x2=9.84, P=0.001708), Candida spp (x2=5.2, P=0.02258), Staphylococcus aureus (x2 = 15.6, P= 0.000078), and Providencia spp (x2 = 6, P=0.014306). The overall oral microbial alteration (x2=53, P< 0.00001) was statistically significant. The ratio of pathogenic microorganisms (OR=4, 95%CI:2.3786-7.062 and RR=1.477, 95%CI:1.2478-1.7153) was significantly associated with oral disease. Conclusion: Oral microbial alteration contributes to oral disease. Early detection of oral microbial alteration, and oral diseases are recommended.
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Correlation between platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio with hematological parameters in multiple myeloma patients p. 132
Akanksha Ashok Kalal, Vijith Vittal Shetty, Kailkere Padma Shetty, Meenakshi Arumugam, Reshma Arun Shetty, Nagaraj Venkatesh Kulkarni, Deyyenthody Prashanth Shetty
DOI:10.4103/bbrj.bbrj_275_21  
Background: Multiple myeloma (MM) is a malignant neoplasm of clonal plasma cells. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are prognostic factors and biomarkers of systemic inflammation. The aim of this study was to determine a correlation between NLR, PLR, and hematological parameters in patients with MM. Methods: The clinical data of 50 MM patients were collected from hospital medical records. NLR and PLR were calculated from data obtained from clinical records. Results: The median age was 60 years at diagnosis. The study cohort was divided into two groups based on cutoff points taken from previously published data (NLR: 2.56 and PLR: 157). Erythrocyte sedimentation rate, blood urea, uric acid, platelet count, and absolute neutrophil count were higher in patients with high NLR than in patients with low NLR. A significant association between NLR and blood urea was seen (P < 0.0018). Pearson's correlation analysis revealed a strong positive correlation for blood urea and NLR, uric acid and NLR, and blood urea and PLR. Conclusion: Thus, combined applications of NLR and PLR could be used as a cost-effective diagnostic predictor of MM patients.
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Immunogenicity assessment of antileukemic agent glutaminase from Escherichia coli, Pseudomonas sp., and Bacillus sp. p. 138
Jyotsna Parmar, Shikha Tripathi, Awanish Kumar
DOI:10.4103/bbrj.bbrj_136_21  
Background: L-glutaminase (L-glutaminase or glutamine amidohydrolase: EC 3.5.1.2) is an antileukemic agent which catalyzes the deamidation of glutamine to glutamic acid and ammonia. It is a highly potent antitumor drug solely or in combination with L-asparaginase. In the market, various microbial glutaminases are available, which are used in treatment. The high immunogenicity was reported with microbial glutaminase when they are introduced in the body during the treatment of acute lymphoblastic leukemia (ALL). Methods: This study was aimed to determine the immunogenicity of the less studied enzyme L-glutaminase from Escherichia coli, Pseudomonas sp., and Bacillus sp. to reduce the allergenicity caused by this enzyme. In the present study, we determined the immunogenicity and allergenicity of microbial glutaminase using an immunoinformatics approach to predict immunogenic and allergenic epitopes with their structural analysis also. Results: We found high immunogenicity of glutaminase from these three microbial sources but did not find a significant difference in their immunogenicity, while E. coli glutaminase showed a high relative frequency of allergenic epitopes. Conclusions: In our knowledge, this is the first research report that presented the immunogenic epitopes and structural allergenic determinants that warrant further work to minimize the immune response of glutaminase and could contribute to reducing the side effect and hypersensitivity response of glutaminase during the treatment.
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Expression analysis of genes and MicroRNAs involved in recurrent implantation failure: New noninvasive biomarkers of implantation p. 145
Bahareh Habibi, Marefat Ghaffari Novin, Saghar Salehpour, Mahsa Ghaffari Novin, Samira Mohammadi Yeganeh, Hamid Nazarian
DOI:10.4103/bbrj.bbrj_246_21  
Background: Recurrent implantation failure (RIF) is defined as three or more failed in vitro fertilization attempts and is due to several factors such as oocyte and embryo quality. Methods: Fifty-one RIF patients and 19 controls were selected based on the inclusion criteria. EFNB2, CAMK1D, AREG, and PTGS2 as well as miR-34, miR-145, miR-204-5p, and miR-26-5p were selected since the microRNAs (miRNAs) targeted the genes based on bioinformatic predictions and literature review. Total RNA was extracted from cumulus cells (CCs) and follicular fluid (FF) of the oocytes. We performed real-time polymerase chain reaction to evaluate the expression of the genes and the miRNAs in CC and FF of pregnant and nonpregnant RIF patients. The expression of CAMK1D, AREG, miR-34-5p, and miR-26-5p was higher in CC than FF. Results: The expression of CAMK1D, PTGS2, and miR-26-5p in CC of the pregnant group was higher than FF. The expression of EFNB2, PTGS2, miR-145, and miR-204-5p was lower in the CC, and the expression of EFNB2, AREG, miR-34-5p, mR-145, and miR-204-5p was lower in the FF of the pregnant group. The expression of CAMK1D, AREG, PTGS2, miR-34-5p, and miR-26-5p was higher in the CC and FF of the high quality (HQ) embryos than non-HQ (NHQ) embryos. The expression of EFNB2, miR-145, and miR-204-5p was higher in the CC and FF of the NHQ embryos. The difference was statistically significant for EFNB2 in CC and FF as well as miR-145 in CC. The level of progesterone and prostaglandin E2 in the FF of the pregnant group was higher than their level in the nonpregnant group. Conclusion: CAMK1D expression and overexpression of miR-34-5p and miR-26-5p could be considered as markers of successful pregnancy. In addition, the results show that normal FF treatment of RIF patients may result in the production of high-quality embryos.
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CASE REPORT Top

S-100 negative cutaneous granular cell tumor: A rare case presentation p. 156
Arup Mishra, Uma Banerjee, Manas Talukdar, Bhawna Bhutoria Jain
DOI:10.4103/bbrj.bbrj_230_21  
Cutaneous granular cell tumor (GCT) is an uncommon benign mesenchymal neoplasm of skin constitutes 0.5% of all soft-tissue tumors, presenting as slowly growing papule or nodule. Familial cases and congenital GCT have been reported to be associated with multiple lesions. Classic GCT is usually S-100 and CD 68 positive. Here, we report the case of a 16-year-old male patient presented with a 2-year history of slowly growing firm, nontender, nodular masses all over the body without any lymphadenopathy. Hematoxylin and eosin-stained sections show histological picture of GCT, but it is CD-68 positive and S-100 negative on immunohistochemistry. Due to its rare immunohistological feature, we are presenting this case. Documentation and reporting of such aberrant cases are necessary for further study on actual origin of these tumors which may aid for better management in future.
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