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The incidence and death toll due to SARS-CoV-2 infection varied time-to-time; and depended on several factors, including severity (viral load), immune status, age, gender, vaccination status, and presence of comorbidities. The RNA genome of SARS-CoV-2 has mutated and produced several variants, which were classified by the SARS-CoV-2 Interagency Group (SIG) into four major categories. The first category; “Variant Being Monitored (VBM)”, consists of Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Epsilon (B.1.427, B.1.429), Eta (B.1.525), Iota (B.1.526), Kappa (B.1.617.1), Mu (B.1.621), and Zeta (P.2); the second category; “Variants of Concern” consists of Omicron (B.1.1.529). The third and fourth categories include “Variants of Interest (VOI)”, and “Variants of High Consequence (VOHC)”, respectively, and contain no variants classified currently under these categories. The surge in VBM and VOC poses a significant threat to public health globally as they exhibit altered virulence, transmissibility, diagnostic or therapeutic escape, and the ability to evade the host immune response. Studies have shown that certain mutations increase the infectivity and pathogenicity of the virus as demonstrated in the case of SARS-CoV-2, the Omicron variant. It is reported that the Omicron variant has >60 mutations with at least 30 mutations in the Spike protein (“S” protein) and 15 mutations in the receptor-binding domain (RBD), resulting in rapid attachment to target cells and immune evasion. The spread of VBM and VOCs has affected the actual protective efficacy of the first-generation vaccines (ChAdOx1, Ad26.COV2.S, NVX-CoV2373, BNT162b2). Currently, the data on the effectiveness of existing vaccines against newer variants of SARS-CoV-2 are very scanty; hence additional studies are immediately warranted. To this end, recent studies have initiated investigations to elucidate the structural features of crucial proteins of SARS-CoV-2 variants and their involvement in pathogenesis. In addition, intense research is in progress to develop better preventive and therapeutic strategies to halt the spread of COVID-19 caused by variants. This review summarizes the structure and life cycle of SARS-CoV-2, provides background information on several variants of SARS-CoV-2 and mutations associated with these variants, and reviews recent studies on the safety and efficacy of major vaccines/vaccine candidates approved against SARS-CoV-2, and its variants.

The Aurora kinases represent a group of serine/threonine kinases which are crucial regulators of mitosis. Dysregulated Aurora kinase B (AurkB) expression, stemming from genomic amplification, increased gene transcription or overexpression of its allosteric activators, is capable of initiating and sustaining malignant phenotypes. Although AurkB level in cells is well-orchestrated, studies that relate to its stability or activity, independent of mitosis, are lacking. We report that AurkB undergoes acetylation in vitro by lysine acetyltransferases (KATs) belonging to different families, namely by p300 and Tip60. The haploinsufficient tumor suppressor Tip60 acetylates two highly conserved lysine residues within the kinase domain of AurkB which not only impinges the protein stability but also its kinase activity. These results signify a probable outcome on the increase in “overall activity” of AurkB upon Tip60 downregulation, as observed under cancerous conditions. The present work, therefore, uncovers an important functional interplay between AurkB and Tip60, frailty of which may be an initial event in carcinogenesis.

This article deals with a rare occurrence of Ganglioneuroma of the left cervical sympathetic chain in a 9-year-old girl, presenting with painless paracervical swelling noticed since 7 months. Imaging studies showed a left parapharyngeal mass extending from C1 to C6, displacing the posterior pharyngeal wall and anterolaterally displacing the contents of the carotid sheath, with no significant vascular feeders. A provisional diagnosis of? Neurogenic tumour was established and the patient underwent surgical excision. Histopathologically, the diagnosis of Ganglioneuroma was confirmed.

To study the feasibility of iron and folic acid (IFA) supplementation among tribal adolescent girls and identify factors associated with high compliance. Intervention study with IFA supplementation among tribal adolescent girls of Bijadandi block, Mandla district, Madhya Pradesh, India. Girls (n 274) from twelve villages randomly selected out of 100 potential villages received daily tablets containing iron (iii) hydroxide polymaltose complex equivalent to 100 mg of elemental Fe and 350 μg of folic acid (commercially available as Feritas tablets, marketed by Intas Pharmaceutical Ltd, India). IFA was given for 100 d and supervised by school teachers and anganwadi workers. Compliance was measured using cards and interviews. Community-based iron supplementation programme. Tribal adolescent girls aged 12-19 years. In total 233 girls completed the study. Prevalence of anaemia was reduced from 94 % at baseline to 69 % after the intervention. Compliance rate (>80 tablets) was 89 %. Minor side-effects were reported by three girls, yet they consumed >80 tablets. Factors associated with compliance included fasting during the local festival (χ 2 = 72·74, df 3; P < 0·0001) and counselling (χ 2 = 72·74, df 3; P < 0·0001). Other qualitative factors like social mobilization, timely supply of tablets, quality of tablets (blister pack) and availability of teachers and anganwadi workers were also associated with the compliance and feasibility. High compliance indicates that IFA supplementation with tablets is feasible among the tribal adolescent girls of Bijadandi block, Mandla district.

Rabies is a fatal encephalomyelitis mainly transmitted to humans and other animals by rabid dog bites. Hence, vaccination programs are being instituted for the control of rabies in dogs. Though stray dogs have been vaccinated for years under various programs initiated for control of the disease, the effectiveness of these programs can be ascertained only by assessing the immunity of these dogs. With this in view, a study was conducted to assess the effectiveness of the ongoing mass dog vaccination (MDV) program by the Bengaluru City Municipal Corporation, Bengaluru, India. Whole blood and serum samples (n = 260) from vaccinated stray dogs in 26 wards of 8 corporation zones were tested by rapid fluorescent focus inhibition test (RFFIT) as well as an in-house quantitative indirect enzyme-linked immunosorbent assay (iELISA) for a humoral response and by interferon-gamma (IFN–γ) ELISA for a cellular response. As determined by the cut-off value of 0.5 IU/mL of serum, 71% and 87% of the samples from vaccinated dogs revealed adequate levels of antibodies presumed to confer protection by RFFIT and iELISA, respectively. The sensitivity and specificity of the iELISA were 100% and 63.3%, respectively. The IFN–γ ELISA revealed adequate cellular response in 50% of the samples. The quantitative iELISA was found to be useful in large-scale seromonitoring of MDV programs to aid in the elimination of dog-mediated rabies.

Background The occurrence of life-threatening events in hospitalized patients with tracheostomies are often preventable. Nurses have a vital role in providing consistent tracheostomy care to patients, thereby avoiding complications. This study was conducted to assess the knowledge of nurses in high dependency areas at a tertiary care hospital with regards to tracheostomy care, to train them and to assess the impact of a tracheostomy care teaching module. Methods Purposive sampling techniques were used to recruit 65 nurses from high dependency areas in Father Muller Medical College Hospital. With appropriate informed, a detailed evaluation was conducted with a pre-validated questionnaire that assesses the knowledge, attitude and practices with regards to tracheostomy care. The nurses then underwent a tracheostomy training programme with a teaching module that emphasizes on tracheostomy care, a demonstration and hands on experience in the simulation lab, followed by an OSCE and a post-test. Statistical analysis was done using SPSS version 28 for paired T test and crosstabulation. Results There was a mean increase in test scores, from 7.74 in pretest to 10.66 in post-test which was statistically significant. The comfort and confidence level of nurses after the module, increased by 80% and the OSCE scores were averaged around 73% giving a satisfactory outcome. Conclusion This module significantly increased the quality of tracheostomy tube care provided by nurses thereby improving patient outcome. Small modifications to existing training programs can have a significant impact on overall health care as demonstrated by our study.

Stra13, a basic helix-loop-helix (bHLH) transcription factor is involved in myriad biological functions including cellular growth arrest, differentiation and senescence. However, the mechanisms by which its transcriptional activity and function are regulated remain unclear. In this study, we provide evidence that post-translational modification of Stra13 by Small Ubiquitin-like Modifier (SUMO) dramatically potentiates its ability to transcriptionally repress cyclin D1 and mediate G(1) cell cycle arrest in fibroblast cells. Mutation of SUMO acceptor lysines 159 and 279 located in the C-terminal repression domain has no impact on nuclear localization; however, it abrogates association with the co-repressor histone deacetylase 1 (HDAC1), attenuates repression of cyclin D1, and prevents Stra13-mediated growth suppression. HDAC1, which promotes cellular proliferation and cell cycle progression, antagonizes Stra13 sumoylation-dependent growth arrest. Our results uncover an unidentified regulatory axis between Stra13 and HDAC1 in progression through the G(1)/S phase of the cell cycle, and provide new mechanistic insights into regulation of Stra13-mediated transcriptional repression by sumoylation.

Tumors adapt their phenotypes during growth and in response to therapies through dynamic changes in cellular processes. Connexin proteins enable such dynamic changes during development, and their dysregulation leads to disease states. The gap junction communication channels formed by connexins have been reported to exhibit tumor-suppressive functions, including in triple-negative breast cancer (TNBC). However, we find that connexin 26 (Cx26) is elevated in self-renewing cancer stem cells (CSCs) and is necessary and sufficient for their maintenance. Cx26 promotes CSC self-renewal by forming a signaling complex with the pluripotency transcription factor NANOG and focal adhesion kinase (FAK), resulting in NANOG stabilization and FAK activation. This FAK/NANOG-containing complex is not formed in mammary epithelial or luminal breast cancer cells. These findings challenge the paradigm that connexins are tumor suppressors in TNBC and reveal a unique function for Cx26 in regulating the core self-renewal signaling that controls CSC maintenance. Connexin proteins are usually considered as tumor suppressors. Here, the authors show that connexin 26 (Cx26) regulates the self-renewal of breast cancer stem cells via a ternary complex with FAK and NANOG.

BackgroundHypertrophic cardiomyopathy (HCM) is a genetic heart muscle disease with preserved or increased ejection fraction in the absence of secondary causes. Mutations in the sarcomeric protein-encoding genes predominantly cause HCM. However, relatively little is known about the genetic impact of signalling proteins on HCM.Methods and resultsHere, using exome and targeted sequencing methods, we analysed two independent cohorts comprising 401 Indian patients with HCM and 3521 Indian controls. We identified novel variants in ribosomal protein S6 kinase beta-1 (RPS6KB1 or S6K1) gene in two unrelated Indian families as a potential candidate gene for HCM. The two unrelated HCM families had the same heterozygous missense S6K1 variant (p.G47W). In a replication association study, we identified two S6K1 heterozygotes variants (p.Q49K and p.Y62H) in the UK Biobank cardiomyopathy cohort (n=190) compared with matched controls (n=16 479). These variants are neither detected in region-specific controls nor in the human population genome data. Additionally, we observed an S6K1 variant (p.P445S) in an Arab patient with HCM. Functional consequences were evaluated using representative S6K1 mutated proteins compared with wild type in cellular models. The mutated proteins activated the S6K1 and hyperphosphorylated the rpS6 and ERK1/2 signalling cascades, suggesting a gain-of-function effect.ConclusionsOur study demonstrates for the first time that the variants in the S6K1 gene are associated with HCM, and early detection of the S6K1 variant carriers can help to identify family members at risk and subsequent preventive measures. Further screening in patients with HCM with different ethnic populations will establish the specificity and frequency of S6K1 gene variants.

Antibiotics have been traditionally prescribed for any open head and neck surgery. With classification of wound and wound contamination and various published guidelines the practice is still widely prevalent. Thyroidectomy being a clean surgery does not warrant the use of antibiotics at all. We performed an interventional prospective study to see the occurrence of wound infection in patients who received antibiotic prophylaxis as compared to those who did not. A total of 71 patients were recruited in the study who were randomly divided into two groups, one received antibiotic prophylaxis and other did not. Both the groups did not show any marked change in the incidence of wound infection hence highlighting the unnecessary use of prophylactic antibiotics in thyroid surgeries.