Experimental and theoretical studies of tetramethoxy-p-benzoquinone: infrared spectra, structural and lithium insertion properties

International audienceIn the search for low-polluting electrode materials for batteries, the use of redox-active organic compounds represents a promising alternative to conventional metal-based systems. In this article we report a combined experimental and theoretical study of tetramethoxy-p-benzoquinone (TMQ). In carbonate-based electrolytes, electrochemical behaviour of this compound is characterized by a reversible insertion process located at approximately 2.85 V vs. Li+/Li0. This relatively high potential reactivity, coupled with our effort to develop computational methodologies in the field of organic electrode materials, prompted us to complement these experimental data with theoretical studies performed using density functional theory (DFT). Single crystals of TMQ were synthesized and thoroughly characterized showing that this quinonic species crystallised in the P21/n space group. The experimental crystal structure of TMQ was then used to assess various DFT methods. The structural features and vibrational spectra were thus predicted by using as a whole five common density functionals (PBE, LDA, revPBE, PBEsol, B3PW91) with and without a semi-empirical correction to account for the van der Waals interactions using either Grimme's (DFT-D2) or Tkatchenko-Scheffler (TS) scheme. The most reliable combination of the DFT functional and the explicit dispersion correction was chosen to study the Li-intercalated molecular crystal (LiTMQ) with the view of indentifying Li insertion sites. A very close agreement with the experiment was found for the average voltage by using the most stable relaxed hypothetical LiTMQ structure. Additionally, a comparison of vibrational spectra gained either for TMQ molecule and its dimer in gas phase or through periodic calculation was undertaken with respect to the experimentally measured infrared spectra. The topological features of the bonds were also investigated in conjunction with estimates of net atomic charges to gain insight into the effect of chemical bonding and intermolecular interaction on Li intercalation. Finally, π-electron delocalization of both quinone and alkali salts of p-semiquinone were determined using the Harmonic Oscillator model of Aromaticity (HOMA) or aromatic fluctuation index (FLU) calculations

PLoS Negl Trop Dis

International audienc

Sr2V3O9 and Ba2V3O9: quasi one-dimensional spin-systems with an anomalous low temperature susceptibility

The magnetic behaviour of the low-dimensional Vanadium-oxides Sr2V3O9 and Ba2V3O9 was investigated by means of magnetic susceptibility and specific heat measurements. In both compounds, the results can be very well described by an S=1/2 Heisenberg antiferromagnetic chain with an intrachain exchange of J = 82 K and J = 94 K in Sr2V3O9 and Ba2V3O9, respectively. In Sr2V3O9, antiferromagnetic ordering at T_N = 5.3 K indicate a weak interchain exchange of the order of J_perp ~ 2 K. In contrast, no evidence for magnetic order was found in Ba2V3O9 down to 0.5 K, pointing to an even smaller interchain coupling. In both compounds, we observe a pronounced Curie-like increase of the susceptibility below 30 K, which we tentatively attribute to a staggered field effect induced by the applied magnetic field. Results of LDA calculations support the quasi one-dimensional character and indicate that in Sr2V3O9, the magnetic chain is perpendicular to the structural one with the magnetic exchange being transferred through VO4 tetrahedra.Comment: Submitted to Phy. Rev.

Extrakorporale hydrostatische Hochdruckbehandlung als neues Verfahren zur Desinfektion infizierter Knochenpräparate

Background: Allogeneic bone transplantation is at risk of infection, and established disinfection methods typically compromise bone quality. High hydrostatic pressure (HHP) is well established for disinfection in food technology, and also it does protect biomechanical and biological properties of bone. This study is the first investigation of HHP regarding disinfection of bone biopsies. Materials and methods: Bone biopsies of 34 patients with chronic infections were subjected to HHP and assessed for persisting bacterial growth. In series 1, bone biopsies were proceeded directly to HHP (10 min; maximal pressure P-max 600 MPa). In series 2, HHP was applied after 5-day incubation in growth media (10 min or 2 x 30 min; P-max 600 MPa). Furthermore, HHP-induced changes of bacterial morphology on artificially infected bone samples were evaluated by scanning electron microscopy (SEM). Results: For series 1, 71% of the bone samples were sterilised by HHP (n = 17), compared to 38% of the untreated control samples, which were obtained during the same surgery (n = 8). For series 2, after prior incubation, HHP disinfected 7% of the bone specimens (n = 55), all control samples showed bacterial growth (n = 33). Destruction of cell wall integrity of Gram-negative strains was observed by SEM. Conclusion: The effectiveness of HHP for bone disinfection should be improved by optimising treatment parameters. Infections with barosensitive Gram-negative bacteria or yeast might represent possible clinical indications

Electronic Sensors for Assessing Interactions between Healthcare Workers and Patients under Airborne Precautions

International audienceBackground: Direct observation has been widely used to assess interactions between healthcare workers (HCWs) and patients but is time-consuming and feasible only over short periods. We used a Radio Frequency Identification Device (RFID) system to automatically measure HCW-patient interactions. Methods: We equipped 50 patient rooms with fixed sensors and 111 HCW volunteers with mobile sensors in two clinical wards of two hospitals. For 3 months, we recorded all interactions between HCWs and 54 patients under airborne precautions for suspected (n=40) or confirmed (n=14) tuberculosis. Number and duration of HCW entries into patient rooms were collected daily. Concomitantly, we directly observed room entries and interviewed HCWs to evaluate their self- perception of the number and duration of contacts with tuberculosis patients. Results: After signal reconstruction, 5490 interactions were recorded between 82 HCWs and 54 tuberculosis patients during 404 days of airborne isolation. Median (interquartile range) interaction duration was 2.1 (0.8-4.4) min overall, 2.3 (0.8-5.0) in the mornings, 1.8 (0.8-3.7) in the afternoons, and 2.0 (0.7-4.3) at night (P,1024). Number of interactions/day/HCW was 3.0 (1.0-6.0) and total daily duration was 7.6 (2.4-22.5) min. Durations estimated from 28 direct observations and 26 interviews were not significantly different from those recorded by the network. Conclusions: The RFID was well accepted by HCWs. This original technique holds promise for accurately and continuously measuring interactions between HCWs and patients, as a less resource-consuming substitute for direct observation. The results could be used to model the transmission of significant pathogens. HCW perceptions of interactions with patients accurately reflected reality

High doses of favipiravir in two men survivors of Ebola virus disease carrying Ebola virus in semen in Guinea

BACKGROUND: Persistence of Ebola virus (EBOV) in semen remains of deep concern, as sexual transmission of EBOV seems plausible up to 6 months after acute phase of Ebola virus disease (EVD). Favipiravir, a broad spectrum antiviral product, has been evaluated in reducing EVD mortality in Guinea in 2014-2015 in the JIKI trial, the pharmacokinetic results of which suggest that an increase of dose might be necessary to achieve a therapeutically relevant exposure. In FORCE trial, we aimed at evaluating the tolerance and activity of high doses of favipiravir in male EVD survivors with EBOV RNA detection in semen in Guinea. CASE: In 2016, we launched a phase IIa open-labeled multicenter dose escalation study. Male survivors of EVD with EBOV RT-PCR positive on semen received a loading dose of 2400 mg BID of favipiravir on day 1 then a maintenance dose of 1800 mg BID from day 2-14. The primary outcome was the tolerance, assessed daily during period treatment and up to day 90. Unfortunately only two participants were included and the trial was stopped for lack of recruitment. No clinical adverse event of grade 3/4 was reported for both patients. One patient experienced a grade 3 hypocalcemia at day 10 and 14. CONCLUSIONS: High doses of favipiravir were well tolerated in these two participants. Better characterized tolerance and pharmacokinetics of high doses of favipiravir are of utmost importance considering that favipiravir is a candidate treatment for a variety of emerging severe viral diseases with poor prognosis

Endpoints for randomized controlled clinical trials for COVID-19 treatments

Background: Endpoint choice for randomized controlled trials of treatments for novel coronavirus-induced disease (COVID-19) is complex. Trials must start rapidly to identify treatments that can be used as part of the outbreak response, in the midst of considerable uncertainty and limited information. COVID-19 presentation is heterogeneous, ranging from mild disease that improves within days to critical disease that can last weeks to over a month and can end in death. While improvement in mortality would provide unquestionable evidence about the clinical significance of a treatment, sample sizes for a study evaluating mortality are large and may be impractical, particularly given a multitude of putative therapies to evaluate. Furthermore, patient states in between “cure” and “death” represent meaningful distinctions. Clinical severity scores have been proposed as an alternative. However, the appropriate summary measure for severity scores has been the subject of debate, particularly given the variable time course of COVID-19. Outcomes measured at fixed time points, such as a comparison of severity scores between treatment and control at day 14, may risk missing the time of clinical benefit. An endpoint such as time to improvement (or recovery) avoids the timing problem. However, some have argued that power losses will result from reducing the ordinal scale to a binary state of “recovered” versus “not recovered.” Methods: We evaluate statistical power for possible trial endpoints for COVID-19 treatment trials using simulation models and data from two recent COVID-19 treatment trials. Results: Power for fixed time-point methods depends heavily on the time selected for evaluation. Time-to-event approaches have reasonable statistical power, even when compared with a fixed time-point method evaluated at the optimal time. Discussion: Time-to-event analysis methods have advantages in the COVID-19 setting, unless the optimal time for evaluating treatment effect is known in advance. Even when the optimal time is known, a time-to-event approach may increase power for interim analyses. © The Author(s) 2020

CPT Pharmacometrics Syst Pharmacol

We modeled the viral dynamics of 13 untreated patients infected with SARS-CoV-2 to infer viral growth parameters and predict the effects of antiviral treatments. In order to reduce peak viral load by more than 2 logs, drug efficacy needs to be greater than 90% if treatment is administered after symptom onset; an efficacy of 60% could be sufficient if treatment is initiated before symptom onset. Given their pharmacokinetic/pharmacodynamic properties, current investigated drugs may be in a range of 6-87% efficacy. They may help control virus if administered very early, but may not have a major effect in severe patients