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   Table of Contents - Current issue
Coverpage
October-December 2020
Volume 4 | Issue 4
Page Nos. 269-366

Online since Wednesday, December 30, 2020

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REVIEW ARTICLES  

Understanding the genetics of gastric and esophageal cancer using Drosophila melanogaster as a model organism Highly accessed article p. 269
Preeti Thiyagarajan, Venkatachalam Deepa Parvathi
DOI:10.4103/bbrj.bbrj_57_20  
Drosophila melanogaster, a vicious model, has helped in significant discoveries about several conserved mechanisms. The insect intestine had remained unexplored until the identification of adult somatic stem cells which triggered the invention of genetic amenability of this insect organ in powerful and artistic ways. A variety of mechanisms within the fruit flies' intestine are conserved in human gastrointestinal systems and will, therefore, become relevant within the context of human pathologies such as gastrointestinal cancers and obesity. In line with current guidelines, maintaining a high degree of suspicion of hereditary etiology (genetic involvement) helps in disease diagnosis. In this review, genetics of two crucial cancers are discussed. Mutation or transcriptional silencing of the cadherin-1 (CDH1) gene and tumor protein p53 gene is related to familial diffuse gastric cancer (GC) and esophageal adenocarcinoma, respectively. Testing for CDH1 mutations in patients with familial clustering of hereditary diffuse GC has proven consistent. Further studies on the expression and also the alteration within the proteins within the E-CDH pathways and Hippo pathway may function as biomarkers for early detection. Dysregulation of various mechanisms ends up in invasion, proliferation, and metastases. The promise of targeted therapy and personalized medicine in improving the clinical outcome is now closer than it has ever been.
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General awareness on hantavirus infection: A brief review p. 274
Rashed Noor
DOI:10.4103/bbrj.bbrj_110_20  
Hantavirus is a negative, stranded RNA virus, largely known to be transmitted to humans, especially working in forestry from the rodents. The human-to-human transmission of this virus is still in obscure; however, upon transmission of this virus from the rodent fluids, its fatality is noticed mainly through the hyperinflammatory syndrome and the cardiopulmonary syndrome. Several reports revealed an alternation of the immune response including the natural killer cells, CD8+ T cells, neutrophils, and several cytokines during the viral pathogenesis. Unlike the other emerging viruses including the currently ongoing novel coronavirus (COVID-19) pandemic, the global mortality rate due to hantavirus infection is so far very low, which, in turn, made the general people all around the world know a very little about this virus. Besides, no effective antiviral therapy including vaccines has yet been developed to combat the viral infection. Lots of comprehensive reports elaborately discussed this virus pointing toward its dreadfulness. The current review discussed the fatal effects of the hantavirus infection in a relatively simplistic way, which can be easily understood by the general community who are still unaware of the risks posed by this relatively uncommon virus.
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Genetic makeup and associated virulence posed by the enteropathogenic Escherichia coli and the Enterotoxigenic Escherichia coli pathotypes p. 280
Syeda Muntaka Maniha, Rashed Noor
DOI:10.4103/bbrj.bbrj_70_20  
The enteropathogenic Escherichia coli (EPEC) is known to trigger diarrhea in infants, whereas the enterotoxigenic E. coli (ETEC) accounts for the children's diarrhea and the travelers' diarrhea. Transmission of the pathogenic bacteria usually occurs in a fecal–oral route usually originating from the poultry items. Thus, the study relating these E. coli pathotypes to the required virulence factors would be of great interest for the welfare of mass public health. Although the reports on the food-oriented pathogenic E. coli so far are actually uncountable, the present review especially concentrated on the genetics of virulence factors required for the pathogenesis by EPEC and ETEC based on the information given by the previous literature. The review focused on the expressional regulation of the components required for the EPEC pathophysiological impact on humans. The necessary studies correlating the genome with the expression of the virulence factors have been well discussed.
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Does epstein–barr virus participate in the development of breast cancer? A brief and critical review with molecular evidences p. 285
Muhammad Usman, Yasir Hameed, Mukhtiar Ahmad
DOI:10.4103/bbrj.bbrj_101_20  
The oncogenic potential of Epstein–Barr virus (EBV) has been well studied in human breast cancer (BC) so far but still controversies surround its role. In the present study, we aimed to perform a comprehensive and critical review of the results and methodologies used by the previous studies to identify the association between EBV markers with human breast. We also proposed a criterion based on the Bradford hill postulates of causation and EBV prevalence to evaluate the results of previous studies for proving EBV etiological role in breast cancer. A PubMed search engine-based strategy was implemented to retrieve all the relevant studies. In total, 50 original studies were retrieved. Out of which 20 were case–control studies while others were not. The positivity ratios of EBV detection in breast cancer samples varied study wise. Few studies did not identify the EBV markers in breast cancer while others identified it with different detection positivity ratios varying from 2.9% to 75.8%. Similarly, the EBV detection positivity ratios in normal and benign samples also varied between 0%–35% and 0%–75.8%, respectively. In total, 18 out of 20 case–control studies, the positivity ratios of EBV detection were higher or equal in breast samples as compared to controls, while two case–control studies also report the opposite results. However, the odds ratios and confidence intervals were not reported. The results failed to prove EBV as a potential biomarker of breast cancer but rather suggested its role as a cause-effect or at least co-participant.
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The role of estrogen in breast cancer p. 293
Roaa Khadem, Fatimah Chassab Mahdi, Karrar AI-Mosawi, Ali Abdul Hussein S. AL-Janabi
DOI:10.4103/bbrj.bbrj_59_20  
Estrogen has a significant effect on the development of breast cancer. Its activities in the human body are mainly performed by binding to cellular estrogen receptor (ER). Breast cancer in relate to the presence of ER can be divided into ER-positive and ER-negative breast cancer. The role of estrogen and its receptors in the development of breast cancer will be discussed in this review.
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Influence of De novo mutation in autism p. 297
Ann Mary Alappat Sanjeev, Bharathi Kathirvel, Kaviya Mohandass, Vijaya Anand Arumugam
DOI:10.4103/bbrj.bbrj_63_20  
Autism and autism spectrum disorders (ASD) affects the areas of social awareness and interaction, verbal and nonverbal communication, and behaviors and interests, which are grouped among neurobehavioral disorders. One in 68 children is affected with ASD according to the estimate from the Center for Disease Control and Prevention's autism and developmental disabilities monitoring network and an increasing prevalence observed worldwide. A characteristic heterogeneity in ASD determined genetic variability as a major contributor. Whole-exome sequencing of ASD individuals revealed that discrete de novo mutation (single-nucleotide variation or small indels) also contribute to the overall genetic risk of ASD apart from rare genetic variation affecting single nucleotides of protein-coding DNA or rare genomic copy number variants as assessed through other high-throughput genomic methods. These genes are involved in synaptic transmission and regulated during brain development by acting upstream or downstream of Wingless- related integration site (WNT), bone morphogenetic proteins/transforming growth factor-β, sonic hedgehog, fibroblast growth factor, and retinoic acid signaling pathways. The current review focuses on genes involved in synaptic function, undergoing de novo mutation leading to ASD condition.
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FNCas9 editor-linked uniform detection assay: An innovative COVID-19 sleuth p. 302
Tarun Kumar Suvvari, MD Nawaz, Mani Kruthika Mantha
DOI:10.4103/bbrj.bbrj_200_20  
Relying on traditional diagnostic approaches like quantitative polymerase chain reaction is not appropriate for both time and cost in sudden outbreaks and pandemics such as COVID-19. In such cases, diagnostic approaches through rapid sequencing of pathogenic DNA and RNA are important for accelerated clinical prognosis. FNCas9 Editor-Linked Uniform Detection Assay (FELUDA) is one such diagnostic approach toward the pathogenic genome, developed by CSIR-IGIB. FELUDA is a paper strip diagnostic test like pregnancy, based on clustered regularly interspaced short palindromic repeats/Cas technology of gene editing. FELUDA showed 96% sensitivity and 98% specificity across all range of viral loads in clinical samples. Due to its low cost, it can drastically reduce the Indian budget toward the rapid testing and COVID-19 diagnostic kits.
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ORIGINAL ARTICLES Top

Phytochemical and antioxidant assessments of Dioscorea bulbifera stem tuber p. 305
Othuke Bensandy Odeghe, Elias Adikwu, Chioma Cynthia Ojiego
DOI:10.4103/bbrj.bbrj_96_20  
Background: Dioscorea bulbifera (D. bulbifera) is used in traditional medicine for the treatment of many disease conditions. However, there is a paucity of information on the antioxidant potential of its stem tuber. Methods: The antioxidant activity of the methanolic extract of D. bulbifera stem tuber was evaluated by measuring its ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, superoxide anion radical (O2-) and nitric oxide (NO) radical. It was also analyzed for bioactive secondary metabolites using standard qualitative and quantitative spectrophotometric methods. Results: The extract showed total phenolic content (0.243 ± 0.052 mg) gallic acid equivalent compared to tannins content (0.259 ± 0.034 mg). Low flavonoid contents (0.060 ± 0.025 mg) quercetin equivalent (QE) and high flavonol contents (1.399 ± 0.075 mg) QE were found in the extract. The extract showed a potent concentration-dependent DPPH radical inhibitory potential with maximal inhibition activity (69.39 ± 1.62%) at 5000 μg/mL compared to ascorbic acid with maximal inhibition activity (88.9 ± 2.67%) at the same concentration. The extract produced maximal O2- anion inhibitory activity (52.86 ± 0.68%) at 2500 μg/mL compared to quercetin with maximal inhibitory activity (68.23 ± 0.41%) at the same concentration. The extract exhibited NO activity in a dose-depend fashion when compared to α-tocopherol. Conclusion: These results showed that D. bulbifera stem tuber extract contains bioactive secondary metabolites with potent-free radical scavenging activity, which could be extracted and standardized for use as food, medicine, and in industries.
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Detailed analyses about predictive value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in invasive lobular breast cancer p. 312
Esra Arslan, Tamer Aksoy
DOI:10.4103/bbrj.bbrj_72_20  
Backgrounds: Management of invasive lobular breast cancer (ILC) is limited with only using standard uptake value (SUV) max of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography. We aimed detailed predictive, prognostic and clinical value of parameters, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) with survival data. Methods: Forty-nine ILC was included in this study. SUVmax, MTV, and TLG documented in molecular and histopathological subtypes. SUVmax, MTV, and TLG compared with nodal involvement, distant metastasis, estrogen receptor (ER), progesterone receptors (PR) and HER status, Ki-67 and survival data. Results: 61.2% luminal A, 36.7% luminal B and 2.0% TN. 53.1% classic and 46.9% pleomorphic. 93.9% ER + and 81.6% had e-cadherin loss. Mean SUVmax was 8.32 ± 4.73. No statistically significant relationship found between classical and pleomorphic with SUVmax (P = 0.616). FDG uptake found significantly higher with tumor >2 cm (P = 0.039). Luminal B SUVmax significantly higher than luminal A (P = 0.013). PR-, Ki-67 high expression, axillary involvement and luminal B significantly reduced survival time (P = 0.034, 0.019, 0.032, and 0.005, respectively). Statistically significant correlation found between high MTV and TLG, tumor diameter (TD) (P = 0.001 and 0.000, respectively). Conclusions: Loss e-cadherin and pleomorphic types did not affect the prognosis. ILC shows low FDG sensitivity compared other breast cancer types, it found to be significantly associated with prognostic factors; TD, molecular subtype, Ki-67 and metastasis. Although volumetric parameters did not add extrapredictive value to FDG involvement pattern, it was found that method remains in diagnosis, staging, and treatment follow-up of ILC.
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Synthesis, characterization, and In vitro antibacterial activity and molecular docking studies of N4, N4'-dibutyl-3,3'-dinitro-[1,1'-Biphenyl]-4,4'-diamine p. 318
K Muddukrishnaiah, V Vijayakumar, B Samuel Thavamani, VP Shilpa, N Radhakrishnan, Heba S Abbas
DOI:10.4103/bbrj.bbrj_52_20  
Background: Resistant growth is recognized as a significant public health hazard to human health worldwide among the most critical bacterial diseases. The evolving multidrug-resistant species are now commonly found in community settings, not just in the hospital area, which means that antibiotic bacteria reservoirs are beyond the hospital. Aim: In this study, we synthesized novel N4, N4'-dibutyl-3,3'-dinitro-[1,1'-biphenyl]-4,4'-diamine from 3,3'-dinitro-[1,1'-biphenyl]-4,4'-diamine and evaluation of its antimicrobial activity against clinical bacteria. Methods: Single-step synthesis of novel N4, N4'-dibutyl-3,3'-dinitro-[1,1'-biphenyl]-4,4'-diamine from 3,3'-dinitro-[1,1'-biphenyl]-4,4'-diamine and well characterized using spectroscopic methods, namely FT-IR, NMR, mass spectrometry, and CHNS. Besides, prepared compound molecular docking investigations, molecular physicochemical, absorption, distribution, metabolism, and excretion (ADME) analysis were also carried out. Results and Discussion: Novel Synthesized N4, N4'-dibutyl-3,3'-diaminobenzidine (DAB) was conducted for antibacterial activity against clinical Klebsiella spp. and Staphylococcus aureus and Pseudomonas spp. by the disc-diffusion method and followed by serial dilution method. N4, N4'-dibutyl-3,3'-DAB showed bacteriostatic action of 500 μg/ml, 1000 μg/ml for Klebsiella spp. and Staphylococcus aureus. The molecular physicochemical investigation exhibited that 1 violation and ADME analysis presented a low gastro intestinal effect. Docking investigations disclosed the capability of synthesized molecule potential to dock with beta-lactamase protein through patch dock methodology. Conclusion: N4, N4'-dibutyl-3,3'-DAB is the novel compound that was found to be attractive for the “drug hunters” as a potential agent for the management of infectious diseases against the human pathogens Klebsiella spp. and Staphylococcus aureus.
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Systematic review and meta-analysis of the association between C-746T and C-703T polymorphisms of the interleukin-5 gene and asthma p. 323
Raghdah Maytham Hameed, Haidar Abdul Amir Najim Abood, Mohanad Mohsin Ahmed
DOI:10.4103/bbrj.bbrj_60_20  
Background: Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. A number of studies have identified the association between interleukin (IL)-5 C-746T and C-703T polymorphisms and asthma risk, however, the results still remain inconclusive. The objective of the present study was to identify the effect of IL-5 polymorphisms in asthma susceptibility. Methods: PubMed and Google Scholar databases were searched. The odds ratio (OR) with its 95% confidence interval (CI) was employed to calculate the effect and strength of association in the random-effects model or fixed-effects model. Results: A total of 4 case–control and 2 cross-sectional studies were screened out, including 1499 asthma patients and 3766 controls. Two single-nucleotide polymorphisms of the IL-5 gene were identified. Our results detected a no significant association between IL-5 C-746T polymorphisms and asthma risk in the total population (CC genotype showed OR = 0.82, 95% CI = 0.67–1.00, P = 0.05, I2 = 0%; CT genotype showed OR = 0.94, 95% CI = 0.78–1.13, P = 0.50, I2 = 24%; and TT genotype showed OR = 0.85, 95% CI = 0.64–1.13, P = 0.27, I2 = 0%) while a significant association between IL-5 C-703T polymorphisms and asthma in children according to review results. Conclusion: The meta-analysis findings suggest a lack of direct association between the IL-5 C-746T polymorphism and asthma and found that C-703T polymorphisms of the IL-5 gene might contribute to asthma risk. Future well-designed case–control studies with a large population and more ethnicities are still needed to estimate the association.
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In Silico modeling and docking study of potential helicase (nonstructural proteins) inhibitors of novel coronavirus 2019 (severe acute respiratory syndrome coronavirus 2) p. 330
Raghunath Satpathy
DOI:10.4103/bbrj.bbrj_149_20  
Background: Currently, the helicase enzyme of novel severe acute respiratory syndrome coronavirus 2019 has been proposed as a potential drug target. This work envisages predicting the three dimensional (3D) structure of helicase (nonstructural protein 13) and screen for the novel inhibitor molecules. Methods: For this purpose, the sequence information of helicase enzyme was obtained from NCBI, and 3D model was predicted using I TASSER server followed by model validation. The helicase enzyme sequence was then used to search for the potential inhibitors in the Drug Bank database. The search resulted eight numbers of probable drug molecules against the receptor. To confirm the binding affinity of the drug molecules, further molecular docking study was conducted using AutoDock Vina software. Results: From the docking result, it was obtained that, among all eight numbers, only the molecule remdesivir shows more binding affinity to the nucleoside triphosphate binding site of helicase enzyme and further confirmed by analysis of amino acid interaction profile. Conclusion: In the present study, it was predicted that, the drug molecule remdesivir can be suitably used as a helicase inhibitor in case of novel severe acute respiratory syndrome coronavirus 2019.
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Diagnostic errors of coronavirus infection: Role of fluorodeoxyglucose positron emission tomography/computed tomography scan p. 337
Abtin Doroudinia, Elinaz Hosseinzadeh, Isa Neshandar Asli, Mehrdad Bakhshayesh Karam, Payam Mehrian
DOI:10.4103/bbrj.bbrj_161_20  
Background: In the era of coronavirus disease 2019 (COVID-19) pandemic, many cases may be misdiagnosed based on their semiology, laboratory tests or chest computed tomography (CT) images and further evaluation might be helpful in appropriately selected cases. Methods:We are discussing usefulness of fluorodeoxyglucose (FDG) positron emission tomography PET/CT scan in appropriately selected suspicious cases of COVID-19 infection. We are discussing two interesting cases on how18F-FDG PET/CT scan might be helpful to avoid COVID-19 infection diagnostic error. Both cases had clinical symptoms suggestive for COVID-19 infection with nonspecific chest CT scan findings including lung nodules, ground glass opacities (GGOs), consolidations, and mosaic perfusion patterns. This case series was approved by our institutional review board and informed consent obtained from both patients. Results: In one case,18F-FDG PET/CT images demonstrated hypermetabolic mostly peripheral GGOs and nodules in both lungs with subsequent evaluation confirming COVID-19 infection. The second case demonstrated right perihilar consolidation, not well appreciated on noncontrast chest CT images in addition to GGOs and further evaluation confirmed diagnosis of poorly differentiated squamous cell carcinoma of the lung. Conclusion: During COVID-19 pandemic, many cases might be misdiagnosed by either clinicians or radiologists. In appropriately selected cases, FDG PET/CT scan may be helpful during COVID-19 outbreak to avoid diagnostic errors.
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Clinico-hematological parameters of sickle hemoglobin hemoglobinopathies and its correlation with ethnicity: A study from Northern Districts of West Bengal p. 342
Bidyut Krishna Goswami, Rajashri Chakrabarty, Subrata Bhattacharjee, Ankita Dhanuka, Sarama Banerjee Goswami, Sudipta Chakrabarti
DOI:10.4103/bbrj.bbrj_164_20  
Background: Inherited disorders of blood include thalassemias and hemoglobinopathies which are one of the major public problems in India. In sickle hemoglobin (HbS) hemoglobinopathies, production of abnormal sickle-shaped red cells results in variable degree of hemolytic anemia along with acute and chronic tissue damage due to vaso-occlusion. The term sickle cell anemia is reserved for homozygous state (SS) for sickle cell gene, while the heterozygous sickle cell trait (AS) has never been considered a disease, has one abnormal gene. Aims: The present study was undertaken to determine the occurrence of HbS hemoglobinopathies in Northern districts of West Bengal and its correlation with ethnicity and different hematological parameters. Methods: A hospital based cross-sectional study was carried out in the Department of Pathology, North Bengal Medical College , along with its thalassemia control unit, over a period of 5 years. Various hematological parameters (Hb, packed cell volume, mean corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], MCH concentration [MCHC], red cell distribution width) were calculated, and hemoglobin variants were determined by high-performance liquid chromatography. Results: 908 (2.19%) patients of sickle cell disease SCD were diagnosed, among a total of 41,549 cases studied. The distribution of HbS hemoglobinopathies were SS-51 (5.6%), AS-727 (80.1%), HbS/beta thalassaemia-109 (12.0%), compound heterozygisity for HbS/Hb E hemoglobinopathy 10 (1.1%) cases. The study revealed that 769 (84.7%) of such HbS variants occurred among the tribal population. Low values of MCV, MCH, and MCHC were noted in both sickle cell trait and in HbS/beta-thalassemia. Conclusion: There is a high occurrence of sickle cell disease in the socioeconomically backward population groups. Mass screening is required in this region for the assessment of different hemoglobin variants among the diverse ethical groups.
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Saliva as an alternate specimen source for the diagnosis of coronavirus disease 2019 in symptomatic patients using cepheid xpert xpress SARS-CoV-2 p. 346
Maya Habous, Rania Medhat Seliem, Laila AlDabal, Firas Al-Najjar, Maimona Elimam, Meera Jainmboo, Bayan Abdalla, Zahra Abdullahi, Ayesha Nasser
DOI:10.4103/bbrj.bbrj_170_20  
Background: Rapid and accurate SARS-CoV-2 diagnostic testing is essential for controlling the ongoing coronavirus disease 2019 (COVID-19) pandemic. The current gold standard for COVID-19 diagnosis is real-time reverse transcription-polymerase chain reaction (RT-PCR) detection of SARS-CoV-2 from nasopharyngeal swab (NPS) specimens. The objective of this study is to assess saliva specimens for the diagnosis of COVID-19 using the GeneXpert® Xpress SARS-CoV-2 assay. Materials and Methods: In June 2020, we prospectively simultaneously collected saliva samples and a standard NPS from 60 patients meeting case definition of COVID-19 in the Emergency Department and from inpatients in Rashid Hospital at Dubai Health Authority during the outbreak of COVID-19. Real-time RT-PCR using the Cepheid Xpert Xpress SARS-CoV-2 was performed, and the results of the two specimens were compared. Results: A total of 60 paired NPS and saliva specimens were tested. An analysis of the agreement between the two specimens demonstrated a 97% observed agreement. 30/28 samples were positive in saliva when compared to the NPS, resulting in a positive percent agreement of 93%. 30/32 samples had a negative saliva and NPS. Two samples demonstrated detectable levels of SARS-CoV-2 nucleic acid in the saliva, but the NPS was negative, resulting in a negative percent agreement of 94%. Conclusion: Our data showed that saliva is an acceptable sensitive and specific alternative source for detecting SARS-CoV-2 nucleic acid and the use of saliva samples is safer and more convenient for the patient. NPS sampling inconsistency may be one of the potential issues for false-negative results.
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Reported patients' attitudes and practices for knowledge of prescribed medications with chronic disease conditions: A cross-sectional study p. 349
Anmar Al-Taie
DOI:10.4103/bbrj.bbrj_174_20  
Background: Patients' medication knowledge plays an essential role in the management of chronic disease conditions. Poor patient's knowledge is associated with low medication adherence, incorrect medication use, improper management of chronic disease conditions, treatment failure, and poor health-related outcomes. The aim of the present study was to assess and compare the attitudes and practices of knowledge about the prescribed medications in patients diagnosed with chronic disease conditions under chronic medication treatment in community pharmacy settings in Baghdad province, Iraq. Methods: A descriptive, cross-sectional study conducted among 384 participants through an interview using a structured 3-parts questionnaire, consisting of 20 items assessing the demographic characteristics, attitudes, and practices of knowledge about the prescribed medications. Results: A total of 384 participants enrolled in this study. About 62.3% of the study participants reported having the previous provision of knowledge about the prescribed medications within the past 12 months. About 61.7% of the study participants reported that the physicians were the primary healthcare professional (HCP) for providing knowledge about the prescribed medications, while 43.5% stated that the medication information leaflets (MILs) were an additional source for providing knowledge about the prescribed medications. There was a difference between the HCP-based knowledge and MIL-based knowledge about the prescribed medications on various elements of medication-related information for the name of the medicine, indication or reason for medicine use, the dosage of the medicine, frequency of the medicine administration and route of medicine administration (100% vs. 43.5%), respectively. Conclusion: The study revealed acceptable attitudes and practices of knowledge about the prescribed medications in patients diagnosed with chronic disease conditions under chronic medication treatment among patients in the Iraqi community; however, there are gaps in the general knowledge about the use of MILs.
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Development of polyepitopic immunogenic contrast against hepatitis C virus 1a-6a genotype by in silico approach p. 355
Zeinab Dehghan, Arezu Lari, Fatemeh Yarian, Shahrzad Ahangarzadeh, Zarrin Sharifnia, Kiana Shahzamani, Solmaz Shahidi
DOI:10.4103/bbrj.bbrj_186_20  
Background: Hepatitis C is a viral disease associated with chronic hepatitis and hepatocellular carcinoma. Hepatitis C virus (HCV) plays a critical role in the pathogenesis of this disease. Nonstructural proteins including NS3, NS4A, and NS5A are important in viral replication and translation. Since recent therapies are not appropriate for anti-HCV activity in humans, the main objective of this study is the use of immunoinformatic approaches for designing a novel multiepitope peptide with antigenic properties and examining it as a vaccine against (1a-6a) genotypes of the virus. These types of studies can be helpful for the development of new vaccine strategies against hepatitis C disease. Methods: The conserved position of nonstructural proteins (NS3/NS4a and NS5A) of HCV genotypes was used for vaccine design. Linear and conformational epitopes of B cell, MHC-I, MHC-II binding epitopes, and interferon-gamma inducing epitopes were determined in the construction of the vaccine. Molecular dynamics (MD) simulation and protein docking multiepitope peptides with toll-like receptor (TLR) 3 and TLR8 were analyzed. Results: MD simulation revealed a stable structure of candidate vaccines. Hence, docking results showed multiepitope peptides interaction with TLR3 and TLR8 and epitopes related to NS3 protein have the most interaction. These analyses suggest that designed vaccines can induce humoral and cellular immune responses against HCV. Conclusions: These analyses suggest that designed vaccines can induce humoral and cellular immune responses against HCV. However, experimental tests are required to evaluate the safety and immunogenicity profile of designed multiepitope vaccines.
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LETTER TO EDITOR Top

Hypolipidemic efficacy of okra (Abelmoschus esculentus) p. 365
Chidiebere Emmanuel Okechukwu
DOI:10.4103/bbrj.bbrj_199_20  
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