A Strategy to Treat COVID-19 Disease With Targeted Delivery of Inhalable Liposomal Hydroxychloroquine: A Preclinical Pharmacokinetic Study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly identified pathogen causing the coronavirus disease 2019 (COVID-19) pandemic. Hydroxychloroquine (HCQ), an antimalarial and anti-inflammatory drug, has been shown to inhibit SARS-CoV-2 infection in vitro and tested in clinical studies. However, achievement of lung concentrations predicted to have in vivo antiviral efficacy might not be possible with the currently proposed oral dosing regimens. Further, high cumulative doses of HCQ raise concerns of systemic toxicity, including cardiotoxicity. Here, we describe a preclinical study to investigate the pharmacokinetics (PKs) of a novel formulation of liposomal HCQ administered by intratracheal (IT) instillation in Sprague-Dawley rats. Compared with unformulated HCQ administered intravenously, liposomal HCQ showed higher (~ 30-fold) lung exposure, longer (~ 2.5-fold) half-life in lungs, but lower blood exposure with ~ 20% of peak plasma concentration (Cmax ) and 74% of area under the curve from 0 to 72 hours (AUC0-72 ) and lower heart exposure with 23% of Cmax and 58% of AUC0-24 (normalized for dose). Similar results were observed relative to IT administration of unformulated HCQ. These PKs result in an animal model that demonstrated the proof of concept that inhalable liposomal HCQ may provide clinical benefit and serve as a potential treatment for COVID-19.

Topological crystalline superconductors in two dimensions.

We propose a general framework to classify the topological edge modes in two dimensional topological crystalline superconductors with time-reversal symmetry, which are protected by different crystalline symmetries. The realization of topological crystalline phases is investigated in the superconductors and a criterion for distinguishing topological phases in crystalline superconductor both with mirror and mirror-inversion symmetry is founded. In these topological phases, Majorana edge modes can be identified along the mirror invariant line, while topological edge modes in the AIII class exist along the mirror-inversion invariant line. Furthermore, for the time-reversal invariant superconductor when only the mirror-inversion symmetry is preserving, topological edge modes in the AIII class with nearly flat band emerge in the mirror-inversion parity subspace.

Paediatric acute kidney injury induced by vancomycin monotherapy versus combined vancomycin and meropenem.

WHAT IS KNOWN AND OBJECTIVE: Increasing reports of the combined use of vancomycin (VAN) and piperacillin/tazobactam leading to higher nephrotoxicity have led to carbapenems being recommended as an alternative option to combine with VAN when nephrotoxicity is a major concern. However, whether carbapenems also increase the nephrotoxicity of VAN is unclear. This study aimed to determine whether meropenem is a suitable drug to combine with VAN based on whether meropenem enhances the nephrotoxicity of VAN. METHODS: This retrospective cohort study enrolled hospitalized children ranging in age from 1 month to 18 years at two tertiary hospitals from 1 February 2017 to 1 February 2018. Patients treated with either VAN or combined VAN and meropenem (VM) for more than 48 hours were eligible for inclusion. Those with underlying kidney diseases or abnormal age-adjusted baseline serum creatinine (SCr) at admission were excluded. Propensity score matching (PSM) was applied to the patients to balance factors associated with acute kidney injury (AKI). In addition, VAN trough concentrations were also compared. AKI was defined as an increase in SCr by ≥50% from baseline or by ≥0.3 mg/dL sustained over at least two consecutive measurements ranging from the time of initiation until 72 hours after the completion of VAN therapy. RESULTS AND DISCUSSION: The eligibility criteria were met by 183 of 243 identified patients: 101 patients received VAN alone and 82 received VM. PSM resulted in 154 hospitalized children being included (77 patients in each group). The incidence of AKI was 10.7% (8/77) in both of the compared groups, while the VAN trough concentration was significantly higher in the VM group (9.0 mg/L) than in the VAN group (6.6 mg/L, P = 0.007) after controlling for confounders. WHAT IS NEW AND CONCLUSION: Despite the elevated VAN trough concentration, meropenem did not increase the nephrotoxicity of VAN and might therefore be an acceptable antibiotic to combine with VAN when necessary.

Fractional charged edge states in ladder topological insulators.

We propose a model of two-leg ladder topological insulator in which the spin-orbit couplings are presented in both intra-chain and inter-chain interactions. The topological phase supports four fractional charged edge states localized at opposite ends of the ladder, which belongs to the chiral symplectic (CII) class protected by time-reversal symmetry and chiral symmetry. In our model, the presence of time-reversal and chiral symmetry generates fourfold degeneracy for the edge states, and the two edge states with same chirality at one end of the ladder each carries half charge. In contrast to the two edge states spatially localized at one end of the ladder being not distinguished, these two edge states can be detected by the momentum density. The experimental scheme for realizing our model with cold atoms in optical lattice is discussed. By introducing a magnetic field in the x direction, the system is driven from CII class to AIII class. In AIII class, there exist two distinct topological phases that exhibit four degenerate edge states and two degenerate edge states in the gap, respectively. As same as the system in CII class, each edge state carries a half charge in AIII class.