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In the quantitative description of viral dynamics within cell cultures and, more broadly, in modeling within-host viral infections, a question that commonly arises is whether the degradation of a fraction of the virus could be disregarded in comparison with the massive synthesis of new viral particles. Surprisingly, quantitative data on the synthesis and degradation rates of RNA viruses in cell cultures are scarce. In this study, we investigated the decay of the human betacoronavirus OC43 (HCoV-OC43) infectivity in cell culture lysates and in fresh media. Our findings revealed a significantly slower viral decay rate in the medium containing lysate cells compared to the fresh medium. This observation suggests that the presence of cellular debris from lysed cells may offer protection or stabilize virions, slowing down their degradation. Moreover, the growth rate of HCoV-OC43 infectivity is significantly higher than degradation as long as there are productive cells in the medium, suggesting that, as a first approximation, degradation can be neglected during early infection., Peer Reviewed, Postprint (published version)

In this work we explain the relevance of the Differential Galois Theory in the semiclassical (or WKB) quantification of some two degree of freedom potentials. The key point is that the semiclassical path integral quantification around a particular solution depends on the variational equation around that solution: a very well-known object in dynamical systems and variational calculus. Then, as the variational equation is a linear ordinary differential system, it is possible to apply the Differential Galois Theory to study its solvability in closed form. We obtain closed form solutions for the semiclassical quantum fluctuations around constant velocity solutions for some systems like the classical Hermite/Verhulst, Bessel, Legendre, and Lamé potentials. We remark that some of the systems studied are not integrable, in the Liouville–Arnold sense., Peer Reviewed, Postprint (author's final draft)

Background: Temocillin is an old antimicrobial that is resistant to hydrolysis by ESBLs but has variable activity against carbapenemase-producing Enterobacteriaceae. The current EUCAST susceptibility breakpoints for Enterobacterales are set at ≤16 mg/L (susceptible with increased exposure) based on a dose of 2 g q8h, but there is limited information on the efficacy of this dose against temocillin-susceptible carbapenemaseproducing Klebsiella pneumoniae isolates. Objectives: To evaluate the efficacy of this dose using a hollow-fibre infection model (HFIM) against six KPC-2- producing clinical isolates of K. pneumoniae. Methods: The isolates were characterized by WGS and temocillin susceptibility was determined using standard and high inoculum temocillin. Mutant frequencies were estimated and temocillin activity was tested in time–kill assays and in the HFIM. At standard conditions, three of the isolates were classified as susceptible (MIC ≤ 16 mg/L) and three as resistant (MIC > 16 mg/L). The HFIM was performed over 3 days to mimic human-like pharmacokinetics of 2 g q8h. Bacterial counts were performed by plating on Mueller–Hinton agar (MHA) and MHA containing 64 mg/L temocillin to detect resistant subpopulations. Results: All isolates showed a reduction in bacterial population of at least 3 log cfu/mL within the first 8 h of simulated treatment in the hollow-fibre assay. Regrowth was observed for the three resistant isolates and one of the susceptible ones. The MIC value for these isolates was higher by at least two dilutions compared with their initial values. Conclusions: These data suggest that an optimized pharmacokinetic regimen may be of clinical interest for the treatment of KPC-2-producing K. pneumoniae susceptible to temocillin. These data showed activity of temocillin against KPC-2-producing K. pneumoniae susceptible to temocillin; however, a dose of 2g q8h administered over 30 min may be inadequate to prevent the emergence of resistant variants.

Almost all viruses, regardless of their genomic material, produce defective viral genomes (DVG) as an unavoidable byproduct of their error-prone replication. Defective interfering (DI) elements are a subgroup of DVGs that have been shown to interfere with the replication of the wild-type (WT) virus. Along with DIs, other genetic elements known as satellite RNAs (satRNAs), that show no genetic relatedness with the WT virus, can co-infect cells with WT helper viruses and take advantage of viral proteins for their own benefit. These satRNAs have effects that range from reduced symptom severity to enhanced virulence. The interference dynamics of DIs over WT viruses has been thoroughly modeled at within-cell, within-host, and population levels. However, nothing is known about the dynamics resulting from the nonlinear interactions between WT viruses and DIs in the presence of satellites, a process that is frequently seen in plant RNA viruses and in biomedically relevant pathosystems like hepatitis B virus and its satellite. Here, we look into a simple phenomenological mathematical model that describes how a WT virus replicates and produces DIs in presence of a satRNA. The WT virus is subject to mechanisms of complementation, competition, and various levels of interference from DIs and the satRNA. Examining the dynamics analytically and numerically reveals three possible regimes: (i) full extinction, (ii) satellite extinction and virus-DIs coexistence and (iii) full coexistence. Assuming DIs replicate faster than the satRNA owed to their smaller size drives to scenario (ii), which implies that DIs could wipe out the satRNA. In addition, a small region of the parameter space exists wherein the system is bistable (either scenarios (ii) or (iii) are concurrently stable). We have identified transcritical bifurcations in the transitions between scenarios (i) to (iii) and saddle–node bifurcations behind the change from bistability to monostability. Despite the model simplicity, Peer Reviewed, Postprint (author's final draft)