The neural mechanisms underlying time perception are of vital importance to a comprehensive understanding of behavior and cognition. Recent work has suggested a supramodal role for beta oscillations in measuring temporal intervals. However, the precise function of beta oscillations and whether their manipulation alters timing has yet to be determined. To accomplish this, we first re-analyzed two, separate EEG datasets and demonstrate that beta oscillations are associated with the retention and comparison of a memory standard for duration. We next conducted a study of 20 human participants using transcranial alternating current stimulation (tACS), over frontocentral cortex, at alpha and beta frequencies, during a visual temporal bisection task, finding that beta stimulation exclusively shifts the perception of time such that stimuli are reported as longer in duration. Finally, we decomposed trialwise choice data with a drift diffusion model of timing, revealing that the shift in timing is caused by a change in the starting point of accumulation, rather than the drift rate or threshold. Our results provide evidence for the intrinsic involvement of beta oscillations in the perception of time, and point to a specific role for beta oscillations in the encoding and retention of memory for temporal intervals.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), initially originated in China in year 2019 and spread rapidly across the globe within 5 months, causing over 96 million cases of infection and over 2 million deaths. Huge efforts were undertaken to bring the COVID-19 vaccines in clinical development, so that it can be made available at the earliest, if found to be efficacious in the trials. We developed a candidate vaccine ZyCoV-D comprising of a DNA plasmid vector carrying the gene encoding the spike protein (S) of the SARS-CoV-2 virus. The S protein of the virus includes the receptor binding domain (RBD), responsible for binding to the human angiotensin converting enzyme (ACE-2) receptor. The DNA plasmid construct was transformed into E. coli cells for large scale production. The immunogenicity potential of the plasmid DNA has been evaluated in mice, guinea pig, and rabbit models by intradermal route at 25, 100 and 500µg dose. Based on the animal studies proof-of-concept has been established and preclinical toxicology (PCT) studies were conducted in rat and rabbit model. Preliminary animal study demonstrates that the candidate DNA vaccine induces antibody response including neutralizing antibodies against SARS-CoV-2 and also provided Th-1 response as evidenced by elevated IFN-γ levels.
Status epilepticus is an emergency; however, prompt treatment of patients with status epilepticus is challenging. Clinical trials, such as the ESETT (Established Status Epilepticus Treatment Trial), compare effectiveness of antiepileptic medications, and rigorous examination of effectiveness of care delivery is similarly warranted. We reviewed the medical literature on observed deviations from guidelines, clinical significance, and initiatives to improve timely treatment. We found pervasive, substantial gaps between recommended and “real-world” practice with regard to timing, dosing, and sequence of antiepileptic therapy. Applying quality improvement methodology at the institutional level can increase adherence to guidelines and may improve patient outcomes.
ZRC-3197 has been developed indigenously by Cadila Healthcare Ltd as a biosimilar adalimumab of originator HUMIRA ®. Biosimilarity has been demonstrated with a comprehensive set of state-of-the-art analytical techniques to characterize the physicochemical and functional properties of ZRC-3197 in comparison with originator HUMIRA ®. The biosimilar ZRC-3197 showed indistinguishable primary and secondary structures with similar level of purity and heterogeneity as compared to that of the originator product. When analyzed, in parallel, the two products were observed to show a high degree of sameness of the carbohydrate structure and charge heterogeneity profile. Both biosimilar ZRC-3197 and the originator HUMIRA ® appeared to show highly comparable key functional properties, as assessed by in vitro cell-based assay and surface plasmon resonance technique. The biosimilar ZRC-3197 exhibited highly similar tumor necrosis factor alpha neutralizing activity as well as binding affinity for FcγRIIIa receptor compared to that of the originator product. The biosimilar ZRC-3197 was observed to show similar level of efficacy and safety profile in rheumatoid arthritis patients, when submitted to a head-to-head double-blind trial, in India, with the originator (reference) product, HUMIRA ®. Based on the demonstrated biosimilarity, market authorization has been granted for ZRC-3197, as a biosimilar of originator HUMIRA ® , in India. Here, we report the characterization of physicochemical and functional properties of the biosimilar ZRC-3197 and originator HUMIRA ® .
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