Search results for: Sharat Musham

Authors: Madhukar Kasarla, Sumit Fogla, Kiran Panuganti, Gaurav Jain, Abhijit Ramanujam, Astha Jain, Shashank Kraleti, Sharat Musham, Arun Chaudhury

Abstract:

Patients have often chosen to travel for care — making pilgrimages to academic meccas and state-of-the-art hospitals for sophisticated surgery. This culture is still persistent in the landscape of US healthcare, with hundred thousand of visitors coming to the shores of United States to seek the high quality of medical care. One of the major challenges in this form of medical tourism has been the language barrier. Thus, an Iraqi patient, with immediate needs of communicating the healthcare needs to the treating team in the hospital, may face huge barrier in effective patient-doctor communication, delaying care and even at times reducing the quality. To circumvent these challenges, we are proposing the use of a state-of-the-art tool, Talk2All, which can translate nearly one hundred international languages (and even sign language) in real time. The tool is an easy to download app and highly user friendly. It builds on machine learning principles to decode different languages in real time. We suggest that the use of Talk2All will tremendously enhance communication in the hospital setting, effectively breaking the language barrier. We propose that vigorous incorporation of Talk2All shall overcome practical challenges in international medical and surgical tourism.

Keywords: language translation, communication, machine learning, medical tourism

Procedia PDF Downloads 179

Authors: Sharat Chandra, Zilong Wang, Ru-Rong Ji, Andrey Bortsov

Abstract:

Chronic pain (CP) therapeutic approaches have limited efficacy. As a result, doctors are prescribing opioids for chronic pain, leading to opioid overuse, abuse, and addiction epidemic. Therefore, the development of effective and safe CP drugs remains an unmet medical need. Voltage-gated sodium (Nav) channels act as cardiovascular and neurological disorder’s molecular targets. Nav channels selective inhibitors are hard to design because there are nine closely-related isoforms (Nav1.1-1.9) that share the protein sequence segments. We are targeting the Nav1.7 found in the peripheral nervous system and engaged in the perception of pain. The objective of this project was to screen a 1.5 million compound library for identification of inhibitors for Nav1.7 with analgesic effect. In this study, we designed a protocol for identification of isoform-selective inhibitors of Nav1.7, by utilizing the prior information on isoform-selective antagonists. First, a similarity search was performed; then the identified hits were docked into a binding site on the fourth voltage-sensor domain (VSD4) of Nav1.7. We used the FTrees tool for similarity searching and library generation; the generated library was docked in the VSD4 domain binding site using FlexX and compounds were shortlisted using a FlexX score and SeeSAR hyde scoring. Finally, the top 25 compounds were tested with molecular dynamics simulation (MDS). We reduced our list to 9 compounds based on the MDS root mean square deviation plot and obtained them from a vendor for in vitro and in vivo validation. Whole-cell patch-clamp recordings in HEK-293 cells and dorsal root ganglion neurons were conducted. We used patch pipettes to record transient Na⁺ currents. One of the compounds reduced the peak sodium currents in Nav1.7-HEK-293 stable cell line in a dose-dependent manner, with IC50 values at 0.74 µM. In summary, our computer-aided analgesic discovery approach allowed us to develop pre-clinical analgesic candidate with significant reduction of time and cost.

Keywords: chronic pain, voltage-gated sodium channel, isoform-selective antagonist, similarity search, virtual screening, analgesics development

Procedia PDF Downloads 95