Tetrodotoxin [HRP]

The prevailing digital landscape, riddled with increasingly complex and ubiquitous cybersecurity threats, poses overwhelming challenges to the secure operation of Information and Communication Technologies (ICT) and ICT-enabled services. To protect their national interest and maintain public confidence in ICT services, it has become critical for all countries to ensure that organizations under their purview are equipped to counter cyber threats effectively. Therefore, all countries have been taking numerous measures and spending significant resources in improving the cybersecurity readiness of organizations operating in their cyber ecosystem. This study is focused on assessing the cybersecurity preparedness of Indian organizations. With this objective, six workshops and two Table Top eXercises (TTX) were conducted. Data were collected from participating entities (n = 103) in moderator-driven, self-assessment mode in the following six dimensions of cybersecurity: Initiatives, Challenges, and Priorities Technical measures Organizational measures Legal measures Capacity-building and Awareness augmentation Cooperation and Information sharing. It is our hope that this study will lead to answering questions pertaining to the identification of areas of priority with regard to cyber preparedness of Indian organizations, recognition of good practices that can be replicated among other organizations and constraints that restrain organizations from going full-tilt.

Naringenin (2S)-5,7-dihydroxy-2-(4-hydroxypheny1)-3,4-dihydro-2H-1-benzopyran-4-one is a natural flavonoid found in fruits from the citrus family. Because (2S)-naringenin is known to racemize, its bioactivity might be related to one or both enantiomers. Computational studies predicted that (2R)-naringenin may act on voltage-gated ion channels, particularly the N-type calcium channel (CaV2.2) and the NaV1.7 sodium channel-both of which are key for pain signaling. Here we set out to identify the possible mechanism of action of naringenin. Naringenin inhibited depolarization-evoked Ca2+ influx in acetylcholine-, ATP-, and capsaicin-responding rat dorsal root ganglion (DRG) neurons. This was corroborated in electrophysiological recordings from DRG neurons. Pharmacological dissection of each of the voltage-gated Ca2+ channels subtypes could not pinpoint any selectivity of naringenin. Instead, naringenin inhibited NaV1.8-dependent and tetrodotoxin (TTX)-resistant while sparing tetrodotoxin sensitive (TTX-S) voltage-gated Na+ channels as evidenced by the lack of further inhibition by the NaV1.8 blocker A-803467. The effects of the natural flavonoid were validated ex vivo in spinal cord slices where naringenin decreased both the frequency and amplitude of sEPSC recorded in neurons within the substantia gelatinosa. The antinociceptive potential of naringenin was evaluated in male and female mice. Naringenin had no effect on the nociceptive thresholds evoked by heat. Naringenin's reversed allodynia was in mouse models of postsurgical and neuropathic pain. Here, driven by a call by the National Center for Complementary and Integrative Health's strategic plan to advance fundamental research into basic biological mechanisms of the action of natural products, we advance the antinociceptive potential of the flavonoid naringenin.