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The COVID-19 pandemic has significantly impacted human lives across the world. In a country like India, with the second highest population in the world, impact of COVID-19 has been diverse and multidimensional. Under such circumstances, vaccination against COVID-19 infection is claimed to be one of the major solutions to contain the pandemic. Understanding of Knowledge, Attitude and Practice (KAP) measures are essential prerequisites to design suitable intervention programs. This paper examines the different KAP factors in Indians towards their decision of vaccine uptake.An online questionnaire was administered to Indian respondents. (Pilot study: n = 100, Main study: n = 221) to assess their existing knowledge on COVID-19 infections and vaccination, attitude and intentions towards COVID-19 vaccines and their decision towards COVID-19 vaccine uptake.The findings highlighted that existing knowledge on COVID-19 infections and vaccination directly impacted their attitude and intention towards vaccination. The attitude and intention towards COVID-19 vaccines directly impacted their practice of undergoing COVID-19 vaccination. Further, there was a statistically significant and considerably large indirect effect of existing knowledge on COVID-19 infections and vaccination on the practice of undergoing COVID-19 vaccination through attitude and intention towards the vaccine. There was no direct effect of Knowledge (existing knowledge on COVID-19 infections and vaccination) on Practice (decision to undergo COVID-19 vaccination). Therefore, Attitude and intention towards COVID-19 vaccine is the primary mediator between Knowledge (existing knowledge on COVID-19 infections and vaccination) and Practice (decision to undergo COVID-19 vaccination).Participants decision towards COVID-19 vaccination decisions are strongly related to their attitude and intentions that confirms the strong role of attitude towards success of COVID-19 vaccination programme. Therefore, 'person-centric' attitude based positive intervention strategies that links their prior knowledge on COVID-19 infections and vaccination must be designed for greater vaccine acceptance amongst Indians.

Healthcare establishments are unique and complex. The Indian healthcare system comprises of public and private healthcare establishments. Different challenges are encountered by the healthcare professionals in their daily operations. The sudden emergence of COVID-19 posed a new threat to the already burdened healthcare system. The pandemic changed the healthcare paradox with newer workplace and societal challenges faced by the healthcare personnel. The purpose of this study is to identify the antecedents of workplace and societal challenges faced by the healthcare personnel. Our study conducted in Kolkata and other adjoining areas of West Bengal included respondents who volunteered for individual in-depth interviews. The sample size was kept at n = 20 after due technical considerations. Freelisting and pile sorting was done to generate clusters. The qualitative study identified five constructs with 18 items under workplace challenges and three constructs with five items under societal/community challenges. Workplace challenges included resource availability, adequacy and allocation, financial issues, perceived managerial ineffectiveness, inconsistent guidelines and perceived occupational stress, while societal/community challenges included dread disease, social adaptiveness and challenges related to essential services. A salience threshold was established and the multidimensional scaling provided four major clusters: financial support and sustainability, adaptive resilience, infection risk mitigation and healthcare facility preparedness. Suggestive actions for the identified challenges were summed as enhanced production of diagnostic kits through public–private partnership models and industrial production reforms. Enhanced testing facility for COVID-19 will help to identify new cases. Financial stresses need long-term sustainable alternative that will avoid pay cuts and unemployment. Treatment regimen, diagnostic protocols, waste disposal guidelines should be worked upon and leading national agencies be consulted for technical support, research and development.

Quality healthcare and satisfaction are gradually emerging as important areas, which need much attention. The factors of patient satisfaction have been identified under varied conditions globally. In the Indian context, one key patient satisfaction factor has been attributed to waiting time. Long waiting time has been one of the major reasons of patient dissatisfaction and assumes significance when associated with paediatric events. The following study has successfully identified key attributes, which are associated with long waiting times within paediatric outpatient department (OPD) settings. The possible implications of the long waiting periods have been recorded through semi-structured interviews, and further in-depth analysis of individual factors were carried out to predict the probable outcomes.The qualitative exploratory study design has helped to understand the perception of parents/care givers (in case of neonates and toddlers) and adolescents, thereby successfully highlighting the need for further study in the patient satisfaction domain involving paediatric population. The various implications which the waiting time has on them have been taken into consideration. The inter-related themes have been identified after analyzing the interviews. These substantiate the fact that designing innovative mitigation strategies on proper and timely communication, updated technological know-how, improvising hospital protocols for better operational processes and coordination among the staff can go a long way in enhancing the patient/parent experience within OPD settings.

l-Asparaginase-II from Escherichia coli (EcA) is a central component in the treatment of acute lymphoblastic leukemia (ALL). However, the therapeutic efficacy of EcA is limited due to immunogenicity and a short half-life in the patient. Here, we performed rational mutagenesis to obtain EcA variants with a potential to improve ALL treatment. Several variants, especially W66Y and Y176F, killed the ALL cells more efficiently than did wild-type EcA (WT-EcA), although nonleukemic peripheral blood monocytes were not affected. Several assays, including Western blotting, annexin-V/propidium iodide binding, comet, and micronuclei assays, showed that the reduction in viability of leukemic cells is due to the increase in caspase-3, cytochrome c release, poly(ADP-ribose) polymerase activation, down-regulation of anti-apoptotic protein Bcl-XL, an arrest of the cell cycle at the G0/G1 phase, and eventually apoptosis. Both W66Y and Y176F induced significantly more apoptosis in lymphocytes derived from ALL patients. In addition, Y176F and Y176S exhibited greatly decreased glutaminase activity, whereas K288S/Y176F, a variant mutated in one of the immunodominant epitopes, showed reduced antigenicity. Further in vivo immunogenicity studies in mice showed that K288S/Y176F was 10-fold less immunogenic as compared with WT-EcA. Moreover, sera obtained from WT-EcA immunized mice and ALL patients who were given asparaginase therapy for several weeks recognized the K288S/Y176F mutant significantly less than the WT-EcA. Further mechanistic studies revealed that W66Y, Y176F, and K288S/Y176F rapidly depleted asparagine and also down-regulated the transcription of asparagine synthetase as compared with WT-EcA. These highly desirable attributes of these variants could significantly advance asparaginase therapy of leukemia in the future.

L-Asparaginase-II from Escherichia coli (EcA) is a central component in the treatment of acute lymphoblastic leukemia (ALL). However, the therapeutic efficacy of EcA is limited due to immunogenicity and a short half-life in the patient. Here, we performed rational mutagenesis to obtain EcA variants with a potential to improve ALL treatment. Several variants, especially W66Y and Y176F, killed the ALL cells more efficiently than did wild-type EcA (WT-EcA), although nonleukemic peripheral blood monocytes were not affected. Several assays, including Western blotting, annexin-V/propidium iodide binding, comet, and micronuclei assays, showed that the reduction in viability of leukemic cells is due to the increase in caspase-3, cytochrome c release, poly(ADP-ribose) polymerase activation, down-regulation of anti-apoptotic protein Bcl-XL, an arrest of the cell cycle at the G0/G1 phase, and eventually apoptosis. Both W66Y and Y176F induced significantly more apoptosis in lymphocytes derived from ALL patients. In addition, Y176F and Y176S exhibited greatly decreased glutaminase activity, whereas K288S/Y176F, a variant mutated in one of the immunodominant epitopes, showed reduced antigenicity. Further in vivo immunogenicity studies in mice showed that K288S/Y176F was 10-fold less immunogenic as compared with WT-EcA. Moreover, sera obtained from WT-EcA immunized mice and ALL patients who were given asparaginase therapy for several weeks recognized the K288S/Y176F mutant significantly less than the WT-EcA. Further mechanistic studies revealed that W66Y, Y176F, and K288S/Y176F rapidly depleted asparagine and also down-regulated the transcription of asparagine synthetase as compared with WT-EcA. These highly desirable attributes of these variants could significantly advance asparaginase therapy of leukemia in the future.

Tuberculosis (TB), an infectious disease caused by the pathogen Mycobacterium tuberculosis (Mtb), kills about 1.5 million people every year worldwide. An increase in the prevalence of drug-resistant strains of Mtb in the last few decades now necessitates the development of novel drugs that combat infections by both drug-sensitive and resistant Mtb. Moreover, as Mtb can persist in host cells by modulating their immune responses, it is essential that anti-TB agents be able to penetrate macrophages and kill the pathogen intracellularly without harming the host cells. In this context, antimicrobial peptides (AMPs) and proteins are being harnessed as anti-infective agents for the treatment of various diseases. Due to their direct and rapid bactericidal activity it is unlikely that pathogens acquire resistance against AMPs. Several short and potent AMP derivatives have been prepared by peptide engineering, and several of them are currently evaluated in clinical trials. The present review summarizes the role of endogenously expressed AMPs and proteins in the treatment of tuberculosis infections. In addition, mechanisms of direct anti-mycobacterial activity, manipulation of host immune responses, and future prospects of AMPs as therapeutic agents are discussed.

Here we studied immunological and antibacterial mechanisms of zinc oxide nanoparticles (ZnO-NPs) against human pathogens. ZnO-NPs showed more activity against Staphylococcus aureus and least against Mycobacterium bovis -BCG. However, BCG killing was significantly increased in synergy with antituberculous-drug rifampicin. Antibacterial mechanistic studies showed that ZnO-NPs disrupt bacterial cell membrane integrity, reduce cell surface hydrophobicity and down-regulate the transcription of oxidative stress-resistance genes in bacteria. ZnO-NP treatment also augmented the intracellular bacterial killing by inducing reactive oxygen species production and co-localization with Mycobacterium smegmatis -GFP in macrophages. Moreover, ZnO-NPs disrupted biofilm formation and inhibited hemolysis by hemolysin toxin producing S. aureus . Intradermal administration of ZnO-NPs significantly reduced the skin infection, bacterial load and inflammation in mice, and also improved infected skin architecture. We envision that this study offers novel insights into antimicrobial actions of ZnO-NPs and also demonstrates ZnO-NPs as a novel class of topical anti-infective agent for the treatment of skin infections. From the Clinical Editor This in-depth study demonstrates properties of ZnO nanoparticles in infection prevention and treatment in several skin infection models, dissecting the potential mechanisms of action of these nanoparticles and paving the way to human applications.