BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine that has been deployed in India. The results of the phase 3 trial have shown clinical efficacy of BBV152. We aimed to evaluate the ...effectiveness of BBV152 against symptomatic RT-PCR-confirmed SARS-CoV-2 infection.
We conducted a test-negative, case-control study among employees of the All India Institute of Medical Sciences (a tertiary care hospital in New Delhi, India), who had symptoms suggestive of COVID-19 and had an RT-PCR test for SARS-CoV-2 during the peak of the second wave of the COVID-19 pandemic in India between April 15 and May 15, 2021. Cases (test-positives) and controls (test-negatives) were matched (1:1) on the basis of age and gender. The odds of vaccination with BBV152 were compared between cases and controls and adjusted for level of occupational exposure (to COVID-19), previous SARS-CoV-2 infection, and calendar time, using conditional logistic regression. The primary outcome was effectiveness of two doses of BBV152 (with the second dose received at least 14 days before testing) in reducing the odds of symptomatic RT-PCR-confirmed SARS-CoV-2 infection, expressed as (1 – odds ratio) × 100%.
Between April 15 and May 15, 2021, 3732 individuals had an RT-PCR test. Of these, 2714 symptomatic employees had data on vaccination status, and 1068 matched case-control pairs were available for analysis. The adjusted effectiveness of BBV152 against symptomatic COVID-19 after two doses administered at least 14 days before testing was 50% (95% CI 33–62; p<0·0001). The adjusted effectiveness of two doses administered at least 28 days before testing was 46% (95% CI 22–62) and administered at least 42 days before testing was 57% (21–76). After excluding participants with previous SARS-CoV-2 infections, the adjusted effectiveness of two doses administered at least 14 days before testing was 47% (95% CI 29–61).
This study shows the effectiveness of two doses of BBV152 against symptomatic COVID-19 in the context of a huge surge in cases, presumably dominated by the potentially immune-evasive delta (B.1.617.2) variant of SARS-CoV-2. Our findings support the ongoing roll-out of this vaccine to help control the spread of SARS-CoV-2, while continuing the emphasis on adherence to non-pharmacological measures.
None.
For the Hindi translation of the abstract see Supplementary Materials section.
Informational discontinuity can have far reaching consequences like medical errors, increased re-hospitalization rates and adverse events among others. Thus the holy grail of seamless informational ...continuity in healthcare has been an enigma with some nations going the digital way. Digitization in healthcare in India is fast catching up. The current study explores the components of informational continuity, its impact on clinical decision-making and captures the general perception among the doctors towards a digital solution.
Cross-sectional study with snowball sampling. A survey questionnaire was developed and validated through a pilot study, then circulated through online platforms. Responses from doctors were obtained through an online Google form for a period of 3 months and analyzed using SPSS 20. The categorical variables were analyzed using Chi-square test.
1413 responses were obtained through a national level survey. Respondents were from a wide range of work experiences, locations, sectors, specialties and patient load. Components of patient records like clinical notes, investigation reports, previous diagnosis and treatment details were rated to be very important. 41% reported about half and 20% reported about 3/4th of their patients do not bring relevant records. Patients from rural areas, visiting state government hospitals and visiting general practitioners were less likely to bring relevant records during consultations. The fallouts of not having timely relevant patient information of the patients include more time per patient, repeat investigations, difficulty to arrive at definitive diagnosis, difficulty to take further treatment decisions and impaired overall clinical decision making which were said to be significant by respondents across the spectrum. The benefits of having timely relevant patient information were also reported consistently across the spectrum. An overwhelming proportion (83%), from across the spectrum, unequivocally expressed their willingness to use digital platforms for accessing patients' relevant medical records.
Prevalence of informational discontinuity and its impact on clinical decision making is significant with definite benefits of having timely relevant medical history. There is strong willingness among the doctors to use digital solution(s) without any extra investment or effort on their part making customized solutions pertinent.
The damage and repair of DNA is a continuous process required to maintain genomic integrity. DNA double-strand breaks (DSBs) are the most lethal type of DNA damage and require timely repair by ...dedicated machinery. DSB repair is uniquely important to nondividing, post-mitotic cells of the central nervous system (CNS). These long-lived cells must rely on the intact genome for a lifetime while maintaining high metabolic activity. When these mechanisms fail, the loss of certain neuronal populations upset delicate neural networks required for higher cognition and disrupt vital motor functions. Mammalian cells engage with several different strategies to recognize and repair chromosomal DSBs based on the cellular context and cell cycle phase, including homologous recombination (HR)/homology-directed repair (HDR), microhomology-mediated end-joining (MMEJ), and the classic non-homologous end-joining (NHEJ). In addition to these repair pathways, a growing body of evidence has emphasized the importance of DNA damage response (DDR) signaling, and the involvement of heterogeneous nuclear ribonucleoprotein (hnRNP) family proteins in the repair of neuronal DSBs, many of which are linked to age-associated neurological disorders. In this review, we describe contemporary research characterizing the mechanistic roles of these non-canonical proteins in neuronal DSB repair, as well as their contributions to the etiopathogenesis of selected common neurological diseases.
This study establishes the physiological role of Fused in Sarcoma (FUS) in mitochondrial DNA (mtDNA) repair and highlights its implications to the pathogenesis of FUS-associated neurodegenerative ...diseases such as amyotrophic lateral sclerosis (ALS). Endogenous FUS interacts with and recruits mtDNA Ligase IIIα (mtLig3) to DNA damage sites within mitochondria, a relationship essential for maintaining mtDNA repair and integrity in healthy cells. Using ALS patient-derived FUS mutant cell lines, a transgenic mouse model, and human autopsy samples, we discovered that compromised FUS functionality hinders mtLig3's repair role, resulting in increased mtDNA damage and mutations. These alterations cause various manifestations of mitochondrial dysfunction, particularly under stress conditions relevant to disease pathology. Importantly, rectifying FUS mutations in patient-derived induced pluripotent cells (iPSCs) preserves mtDNA integrity. Similarly, targeted introduction of human DNA Ligase 1 restores repair mechanisms and mitochondrial activity in FUS mutant cells, suggesting a potential therapeutic approach. Our findings unveil FUS's critical role in mitochondrial health and mtDNA repair, offering valuable insights into the mechanisms underlying mitochondrial dysfunction in FUS-associated motor neuron disease.
RNA-binding proteins (RBPs) are evolutionarily conserved across most forms of life, with an estimated 1500 RBPs in humans. Traditionally associated with post-transcriptional gene regulation, RBPs ...contribute to nearly every known aspect of RNA biology, including RNA splicing, transport, and decay. In recent years, an increasing subset of RBPs have been recognized for their DNA binding properties and involvement in DNA transactions. We refer to these RBPs with well-characterized DNA binding activity as RNA/DNA binding proteins (RDBPs), many of which are linked to neurological diseases. RDBPs are associated with both nuclear and mitochondrial DNA repair. Furthermore, the presence of intrinsically disordered domains in RDBPs appears to be critical for regulating their diverse interactions and plays a key role in controlling protein aggregation, which is implicated in neurodegeneration. In this review, we discuss the emerging roles of common RDBPs from the heterogeneous nuclear ribonucleoprotein (hnRNP) family, such as TAR DNA binding protein-43 (TDP43) and fused in sarcoma (FUS) in controlling DNA damage response (DDR). We also explore the implications of RDBP pathology in aging and neurodegenerative diseases and provide a prospective on the therapeutic potential of targeting RDBP pathology mediated DDR defects for motor neuron diseases and aging.
•Dual Role of RDBPs: The review highlights the dual roles of RDBPs in RNA biology and DDR, emphasizing their crucial involvement in both nuclear and mitochondrial DNA repair processes.•Implications for Neurodegenerative Diseases: It explores how dysfunctions in RDBPs, such as TAR DNA binding protein-43 (TDP43) and fused in sarcoma (FUS), contribute to the pathology of age-associated neurodegenerative diseases like ALS and Alzheimer's disease through mechanisms like protein aggregation and genomic instability.•Potential Therapeutic Targets: The review discusses the therapeutic potential of targeting RDBP-mediated DDR defects, proposing various strategies including small molecule inhibitors, antisense oligonucleotides, and post-translational modifications to mitigate neurodegeneration and aging-related conditions.•Timely and Emerging Research: This review is timely, given the growing recognition of the importance of RDBPs in maintaining genomic stability and their impact on neurological health, providing valuable insights for future research and therapeutic development.
Abstract
Background
: Life cycle costing (LCC) is an excellent decision-making tool that can assist a hospital administrator in seeking more cost-effective decisions to select the best course of ...action. LCC can be defined as “an economic assessment of competing design alternatives, considering all significant costs of ownership over the economic life of each alternative, expressed in equivalent rupees.
Aim
: To determine the LCC of magnetic resonance imaging (MRI) machine at a tertiary care teaching hospital.
Settings and Design
: A descriptive, observational study in MRI scan center of a tertiary care teaching hospital.
Materials and Methods
: LCC analysis (LCCA) was performed to ensure total cost visibility for the entire life span of the MRI scan equipment, which was assumed to be 10 years.
Statistical Analysis
: Data were analyzed using MS Excel.
Results and Conclusions
: The total cost per MRI scan was calculated to be Rs. 2944. It was estimated that the MRI scan center would reach the break-even point by the end of the third year.
To investigate the role of NRF2 signalling in conferring superior prognosis in patients with HPV positive (HPV+ve) head & neck squamous cell carcinomas (HNSCC) compared to HPV negative (HPV−ve) HNSCC ...and develop molecular markers for selection of HPV+ve HNSCC patients for treatment de-escalation trials.
NRF2 activity (NRF2, KEAP1, and NRF2-transcriptional targets), p16, and p53 levels between HPV+ve HNSCC and HPV−ve HNSCC in prospective and retrospective tumor samples as well as from TCGA database were compared. Cancer cells were transfected with HPV-E6/E7 plasmid to elucidate if HPV infection represses NRF2 activity and sensitizes to chemo-radiotherapy.
Prospective analysis revealed a marked reduction in expression of NRF2, and its downstream genes in HPV+ve tumors compared to HPV−ve tumors. A retrospective analysis by IHC revealed significantly lower NQO1 in p16high tumors compared to p16low tumors and the NQO1 expression correlated negatively with p16 and positively with p53. Analysis of the TCGA database confirmed low constitutive NRF2 activity in HPV+ve HNSCC compared to HPV−ve HNSCC and revealed that HPV+ve HNSCC patients with ‘low NQO1’ expression showed better overall survival compared to HPV+ve HNSCC patients with ‘high NQO1’ expression. Ectopic expression of HPV-E6/E7 plasmid in various cancer cells repressed constitutive NRF2 activity, reduced total GSH, increased ROS levels, and sensitized the cancer cells to cisplatin and ionizing radiation.
Low constitutive NRF2 activity contributes to better prognosis of HPV+ve HNSCC patients. Co-expression of p16high, NQO1low, and p53low could serve as a predictive biomarker for the selection of HPV + ve HNSCC patients for de-escalation trials.
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•HPV + ve head and neck tumors are associated with lower constitutive NRF2 activity compared to HPV−ve head and neck tumors.•Ectopic expression of HPV-E6/E7 downregulated NQO1 activity and decreased total GSH levels.•Ectopic expression of HPV-E6/E7 repressed NRF2 activation and enhanced sensitivity to cisplatin and ionizing radiation.•p16high/NQO1low/p53low can be a predictive biomarker for selecting HNSCC patients for treatment de-escalation.
In this study, the adsorption capacities of activated charcoal‐ammonia working pairs at room temperature, at which waste heat is supplied, were studied in a tube‐in‐tube adsorption bed in the ...pressure range of 0.4–10 bar. A double‐pipe adsorption bed was designed, constructed, and utilized for sequential adsorption and desorption of ammonia at 27 °C. Three types of granular activated carbons (GACs) with different particle size distributions were used as adsorbents. Experimental observations showed that the highest adsorption capacity for ammonia was shown by GAC‐2 with broader particle size distribution. The adsorption behaviors of all three adsorbents closely followed the Langmuir model under the operating conditions used in the study.
A single‐bed adsorption cooling system was developed to investigate the adsorption characteristics of ammonia onto three highly porous granular activated carbons (GACs) with different particle size distributions. The Langmuir adsorption isotherm model was utilized in its simplest form to determine the values of the parameters and predict the adsorption behavior of ammonia on the selected adsorbents.
Neoplastic cells often reside in distinctive tumor hypoxia armed with a series of adaptive responses including oxidative stress, defective apoptotic machinery and neoangiogenesis, through that ...further confer cell survival improvement. Plants still acts as reservoir of natural chemicals to provide newer active pharmacophores. Scutellarein is flavones which has wide range of pharmacophoral effects. In our current research, scutellarein employed for targeting oxidative stress mediated tumor angiogenesis and apoptotic nuclear fragmentation. Experimental results revealed that scutellarein has antiproliferative index against multiple cancer cell lines and diminished the oxidative stress and tumor development of murine ascitic lymphoma & inflammatory hepatocellular carcinoma. Eventual consequences lead to reduced neovessel formation by abrogating angiogeneic factors cytokine-VEGF-A, Flt-1, HIF-1α, MMP-2 and MMP-9 and reversing of evading apoptosis by activating caspase-3 activated DNA fragmentation factor (DFF-40) mediated nucleosomal degradation. In summary, our experimental evidences suggest that scutellarein has strong potentiality to attenuate the tumor development by modulating sprouting neovasculature and DFF-40 mediated apoptosis.
•Scutellarein exhibits potent neoplastic effect against ascitic and DEN-induced liver carcinoma in-vivo.•Scutellarein reticence the oxidative stress and angiogenesis on tumor and non-tumor models.•Scutellarein modulates tumor vasculature by altering tumor angiogenic factor’s expressions.•Scutellarein actuates the DFF-40 mediated nucleosomal degradation in DLA tumor.
Recent disruption of medical oxygen during the second wave of coronavirus disease 2019 (COVID-19) has caused nationwide panic. This study attempts to objectively analyze the medical oxygen supply ...chain in India along the principles of value stream mapping (VSM), identify bottlenecks, and recommend systemic improvements.
Process mapping of the medical oxygen supply chain in India was done. Different licenses and approvals, their conditions, compliances, renewals, among others were factored in. All relevant circulars (Government Notices), official orders, amendments, and gazette notifications pertaining to medical oxygen from April 2020 to April 2021 were studied and corroborated with information from Petroleum and Explosives Safety Organization (PESO) official website.
Steps of medical oxygen supply chain right from oxygen manufacture to filling, storage, and transport up to the end users; have regulatory bottlenecks. Consequently, flow of materials is sluggish and very poor information flow has aggravated the inherent inefficiencies of the system. Government of India has been loosening regulatory norms at every stage to alleviate the crisis.
Regulatory bottlenecks have indirectly fueled the informal sector over the years, which is not under Government's control with difficulty in controlling black-marketing and hoarding. Technology enabled, data-driven regulatory processes with minimum discretionary human interface can make the system more resilient.
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