Genomic Variations in SARS-CoV-2 Genomes From Gujarat: Underlying Role of Variants in Disease Epidemiology.

Humanity has seen numerous pandemics during its course of evolution. The list includes several incidents from the past, such as measles, Ebola, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS), etc. The latest edition to this is coronavirus disease 2019 (COVID-19), caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of August 18, 2020, COVID-19 has affected over 21 million people from 180 + countries with 0.7 million deaths across the globe. Genomic technologies have enabled us to understand the genomic constitution of pathogens, their virulence, evolution, and rate of mutation, etc. To date, more than 83,000 viral genomes have been deposited in public repositories, such as GISAID and NCBI. While we are writing this, India is the third most affected country by COVID-19, with 2.7 million cases and > 53,000 deaths. Gujarat is the 11th highest affected state with a 3.48% death rate compared to the national average of 1.91%. In this study, a total of 502 SARS-CoV-2 genomes from Gujarat were sequenced and analyzed to understand its phylogenetic distribution and variants against global and national sequences. Further variants were analyzed from diseased and recovered patients from Gujarat and the world to understand its role in pathogenesis. Among the missense mutations present in the Gujarat SARS-CoV-2 genomes, C28854T (Ser194Leu) had an allele frequency of 47.62 and 7.25% in deceased patients from the Gujarat and global datasets, respectively. In contrast, the allele frequency of 35.16 and 3.20% was observed in recovered patients from the Gujarat and global datasets, respectively. It is a deleterious mutation present in the nucleocapsid (N) gene and is significantly associated with mortality in Gujarat patients with a p-value of 0.067 and in the global dataset with a p-value of 0.000924. The other deleterious variant identified in deceased patients from Gujarat (p-value of 0.355) and the world (p-value of 2.43E-06) is G25563T, which is located in Orf3a and plays a potential role in viral pathogenesis. SARS-CoV-2 genomes from Gujarat are forming distinct clusters under the GH clade of GISAID. This study will shed light on the viral haplotype in SARS-CoV-2 samples from Gujarat, India.

Differential gene expression analysis of HNSCC tumors deciphered tobacco dependent and independent molecular signatures.

Head and neck cancer is the sixth most common cancer worldwide, with tobacco as the leading cause. However, it is increasing in non-tobacco users also, hence limiting our understanding of its underlying molecular mechanisms. RNA-seq analysis of cancers has proven as effective tool in understanding disease etiology. In the present study, RNA-Seq of 86 matched Tumor/Normal pairs, of tobacco smoking (TOB) and non-smokers (N-TOB) HNSCC samples analyzed, followed by validation on 375 similar datasets. Total 2194 and 2073 differentially expressed genes were identified in TOB and N-TOB tumors, respectively. GO analysis found muscle contraction as the most enriched biological process in both TOB and N-TOB tumors. Pathway analysis identified muscle contraction and salivary secretion pathways enriched in both categories, whereas calcium signaling and neuroactive ligand-receptor pathway was more enriched in TOB and N-TOB tumors respectively. Network analysis identified muscle development related genes as hub node i. e. ACTN2, MYL2 and TTN in both TOB and N-TOB tumors, whereas EGFR and MYH6, depicts specific role in TOB and N-TOB tumors. Additionally, we found enriched gene networks possibly be regulated by tumor suppressor miRNAs such as hsa-miR-29/a/b/c, hsa-miR-26b-5p etc., suggestive to be key riboswitches in regulatory cascade of HNSCC. Interestingly, three genes PKLR, CST1 and C17orf77 found to show opposite regulation in each category, hence suggested to be key genes in separating TOB from N-TOB tumors. Our investigation identified key genes involved in important pathways implicated in tobacco dependent and independent carcinogenesis hence may help in designing precise HNSCC diagnostics and therapeutics strategies.

Submental intubation: a new approach in panfacial trauma.

The submental route for endotracheal intubation is an alternative to nasal intubation or tracheo- stomy in the surgical management of patients with complex craniomaxillofacial injuries. The critical indication for submental intubation is the requirement for intra-operative maxillomandibular fixation in the presence of injuries that preclude nasal intubation and in a situation where a tracheostomy is not otherwise required. Maxillomandibular fixation is essential to re-establish dental occlusion for a normal functional result in dentate patients with fractures involving alveolar segments of the jaws. However, maxillomandibular fixation precludes orotracheal intubation. Nasotracheal intubation is often used but is contra-indicated in the presence of skull base fractures and will interfere with the access to certain fracture types. A tracheostomy has a high potential complication rate and in many patients, an alternative to the oral airway is not required beyond the peri-operative period. Submental intuba- tion is a simple and useful technique with low morbidity in selected cases of craniomaxillofacial trauma.

Role of CR1 Knops polymorphism in the pathophysiology of malaria: Indian scenario.

BACKGROUND & OBJECTIVES: Plasmodium falciparum is the leading cause of mortality and causes cerebral malaria associated with sequestration caused by cytoadherence of the trophozoite and schizont-infected erythrocytes to the endothelial cells of the deep vascular beds in the brain. Pathophysiology of malaria is complicated by rosetting. Rosetting is a process of binding of uninfected erythrocytes to the erythrocytes infected with mature asexual parasites and is controlled by expression of complement receptor 1 (CR1) on RBC surface. Various polymorphic forms of CR1 are known including molecular weight polymorphism, red blood cell expression levels/density polymorphism and Knops (KN) polymorphism. The Knops blood group includes several allelic pairs; Knops a and b (Kna and Knb), McCoy a and b (McCa, McCb), Swain-Langley (Sla), and Villien (Vil). Knops phenotype Sl (a-) has been found to rosette less effectively than Sl (a+) and hence suggested to be more protective. P. falciparum cases have not reduced much as compared to the reduction in the total number of malaria cases in the past few years. In addition, P. falciparum is the leading cause for all mortality and most of the morbidity in India. We, therefore, investigated the role of CR1 Knops polymorphism in the pathophysiology of malaria in Indian population. METHODS: A case control approach was used for this study. CAPS (Cleaved amplified polymorphic sequence) methodology was adopted. A total of 100 normal individuals (free from any ailment) and 100 individuals suffering from P. falciparum infection (uncomplicated malaria) were recruited for this study. RESULTS: We found that in Indian population (normal individuals and P. falciparum-infected individuals), only the wild type allele is present. INTERPRETATION & CONCLUSION: We concluded that the process of rosetting in the Indian context could be occurring independently of the effect of Knops polymorphism and in part could be controlled by other polymorphisms of the CR1 gene (density and structural polymorphism).

Complement receptor 1 and the molecular pathogenesis of malaria.

Malaria is a pathogenic infection caused by protozoa of the genus plasmodium. It is mainly confined to sub-Saharan Africa, Asia and South America. This disease claims the life of over 1.5 to 2.7 million people per year. Owing to such a high incidence of malarial infections, there is an urgent need for the development of suitable vaccines. For the development of ideal vaccines, it is essential to understand the molecular mechanisms of malarial pathogenesis and the factors that lead to malaria infection. Genetic factors have been proposed to play an important role in malarial pathogenesis. Complement receptor 1 (CR1) is an important host red blood cell protein involved in interaction with malarial parasite. Various polymorphic forms of CR1 have been found to be involved in conferring protection or increasing susceptibility to malaria infections. Low-density allele (L) of CR1 gave contradictory results in different set of studies. In addition, Knops polymorphic forms Sl (a(+)) and McC (a) have been found to contribute more towards the occurrence of cerebral malaria in malaria endemic regions compared to individuals with Sl (a(-)) / McC (a/b) genotype. This article reviews the research currently going on in this area and throws light on as yet unresolved mysteries of the role of CR1 in malarial pathogenesis.