In vitro and in vivo characterization of erythrosin B and derivatives against Zika virus

Zika virus (ZIKV) causes significant human diseases without specific therapy. Previously we found erythrosin B, an FDA-approved food additive, inhibited viral NS2B−NS3 interactions, leading to inhibition of ZIKV infection in cell culture. In this study, we performed pharmacokinetic and in vivo studies to demonstrate the efficacy of erythrosin B against ZIKV in 3D mini-brain organoid and mouse models. Our results showed that erythrosin B is very effective in abolishing ZIKV replication in the 3D organoid model. Although pharmacokinetics studies indicated that erythrosin B had a low absorption profile, mice challenged by a lethal dose of ZIKV showed a significantly improved survival rate upon oral administration of erythrosin B, compared to vehicle control. Limited structure−activity relationship studies indicated that most analogs of erythrosin B with modifications on the xanthene ring led to loss or reduction of inhibitory activities towards viral NS2B−NS3 interactions, protease activity and antiviral efficacy. In contrast, introducing chlorine substitutions on the isobenzofuran ring led to slightly increased activities, suggesting that the isobenzofuran ring is well tolerated for modifications. Cytotoxicity studies indicated that all derivatives are nontoxic to human cells. Overall, our studies demonstrated erythrosin B is an effective antiviral against ZIKV both in vitro and in vivo.KEY WORDS: Flavivirus, Zika virus, Dengue virus, Antiviral, Protease inhibitor, Erythrosin B     

Structural,thermal, and transport properties of La0.67Sr0.33MnO3 nanoparticles synthesized via the sol–gel auto-combustion technique

Herein, rare-earth manganite, La_0.67Sr_0.33MnO₃, has been prepared by a citric acid-assisted sol–gel auto-combustion method at a maintained pH value of 11. Room-temperature X-ray diffraction (RT-XRD) data analysis revealed a rhombohedral structure for the sample with the space group R3c, which was further confirmed by synchrotron radiation X-ray diffraction (SR-XRD). Rietveld refinement was carried out for both spectra, which confirmed the SR-XRD and RT-XRD results and the various structural parameters. To determine any of the phase transitions in the sample, temperature-dependent X-ray diffraction corresponding to the temperatures of 100 K, 200 K, 250 K, and 325 K was carried out, and no new phase was found. Temperature-dependent Raman characterization confirmed the metallic phase of the sample with the reduced Jahn–Teller distortion. Scanning electron microscopy confirmed the growth in the grain size as a result of a high sintering temperature. Compositional verification was conducted using energy-dispersive analysis of X-ray diffraction (EDAX). Low-temperature dc resistivity measurement showed a metal-insulator transition temperature (T_MI) of ≈178 K. The DSC-specific heat measurement shows the ferromagnetic metallic nature where heat capacity increases with an increase in temperature.

Herein, rare-earth manganite, La_0.67Sr_0.33MnO₃, has been prepared by a citric acid-assisted sol–gel auto-combustion method at a maintained pH value of 11.     

Improving Trauma Care in India: the Potential Role of the Rural Trauma Team Development Course (RTTDC)

The Rural Trauma Team Development Course (RTTDC) was devised to optimize trauma resuscitation training in under-resourced rural institutions. This program appears ideal for India because of its dense traffic, large population, and high frequency of rural trauma. We report on the feasibility and desirability of introducing RTTDC in India. An instructor course for 20 faculties and a provider course for 23 were conducted in New Delhi, India. The courses were evaluated by multiple choice question (MCQ) performance, by rating the modules on a three-point scale (1 = very relevant, 2 = relevant, and 3 = not relevant) for communication skills, principles of performance improvement and patient safety (PIPS), and clinical scenarios. Evaluation questionnaires including desirability of promulgation in India were completed using a five-point Likert Scale (1 = strongly agree, 2 = agree, 3 = neutral, 4 = disagree, and 5 = strongly disagree). Overall written comments were also provided. Both faculty and providers improved post-course MCQ scores (p?<?0.05) with lower scores in the provider group. Seventy-eight percent faculty and 74 % providers rated the communication module very relevant. PIPS was rated very relevant by 72 % faculty and 65 % providers. There were over 150 comments, generally positive with over 90 % of both faculty and providers rating strongly agree to agree that the course be promulgated widely in India. The RTTDC including plans for promulgation was enthusiastically received in India, and its potential for improving trauma care including communication skills and PIPS appears excellent.