Retroviruses package a dimeric genome comprising two copies of the viral RNA. Each RNA contains all of the genetic information for viral replication. Packaging a dimeric genome allows the recovery of genetic information from damaged RNA genomes during DNA synthesis and promotes frequent recombination to increase diversity in the viral population. Therefore, the strategy of packaging dimeric RNA affects viral replication and viral evolution. Although its biological importance is appreciated, very little is known about the genome dimerization process. HIV-1 RNA genomes dimerize before packaging into virions, and RNA interacts with the viral structural protein Gag in the cytoplasm. Thus, it is often hypothesized that RNAs dimerize in the cytoplasm and the RNA-Gag complex is transported to the plasma membrane for virus assembly. In this report, we tagged HIV-1 RNAs with fluorescent proteins, via interactions of RNA-binding proteins and motifs in the RNA genomes, and studied their behavior at the plasma membrane by using total internal reflection fluorescence microscopy. We showed that HIV-1 RNAs dimerize not in the cytoplasm but on the plasma membrane. Dynamic interactions occur among HIV-1 RNAs, and stabilization of the RNA dimer requires Gag protein. Dimerization often occurs at an early stage of the virus assembly process. Furthermore, the dimerization process is probably mediated by the interactions of two RNA-Gag complexes, rather than two RNAs. These findings advance the current understanding of HIV-1 assembly and reveal important insights into viral replication mechanisms.retrovirus | RNA genome | Gag-RNA complex | virus assembly | RNA-binding protein

Purpose: The purpose of this study was to compare how treatment with convalescent plasma (CP) monotherapy, remdesivir (RDV) monotherapy, and combination therapy (CP + RDV) in patients with COVID-19 affected clinical outcomes. Methods: Patients with COVID-19 infection who were admitted to the hospital received CP, RDV, or combination of both. Mortality, discharge disposition, hospital length of stay (LOS), intensive care unit (ICU) LOS, and total ventilation days were compared between each treatment group and stratified by ABO blood group. An exploratory analysis identified risk factors for mortality. Adverse effects were also evaluated. Results: RDV monotherapy showed an increased chance of survival compared to combination therapy or CP monotherapy (p = 0.052). There were 15, 3, and 6 deaths in the CP, RDV, and combination therapy groups, respectively. The combination therapy group had the longest median ICU LOS (8, IQR 4.5-15.5, p = 0.220) and hospital LOS (11, IQR 7-15.5, p = 0.175). Age (p = 0.036), initial SOFA score (p = 0.013), and intubation (p = 0.005) were statistically significant predictors of mortality. Patients with type O blood had decreased ventilation days, ICU LOS, and total LOS. Thirteen treatment-related adverse events occurred. Conclusion: No significant differences in clinical outcomes were observed between patients treated with RDV, CP, or combination therapy. Elderly patients, those with a high initial SOFA score, and those who require intubation are at increased risk of mortality associated with COVID-19. Blood type did not affect clinical outcomes.

This investigation was designed to determine whether significant alterations in the metabolism of nitrogen, calcium, and phosphorus occur in psychiatric patients during the therapeutic administration of electric convulsive treatments. Gour and Chaudhry (1) observed transient changes in serum calcium following grand mal convulsions in a series of patients. Jarvie and Mulligan (2), repeating this experiment in patients receiving muscular relaxants during the administration of E.C.T., failed to demonstrate similar calcium changes. More intimate knowledge of electrolyte metabolism can be obtained by means of balance techniques (3), whereby the degree of retention or loss of a particular substance can be ascertained by maintaining each patient on a constant daily intake and regularly determining the urinary and stool excretion of that substance.

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