Evaluation of Convalescent Plasma for Ebola Virus Disease in Guinea

: In the wake of the recent outbreak of Ebola virus disease (EVD) in several African countries, the World Health Organization prioritized the evaluation of treatment with convalescent plasma derived from patients who have recovered from the disease. We evaluated the safety and efficacy of convalescent plasma for the treatment of EVD in Guinea. : In this nonrandomized, comparative study, 99 patients of various ages (including pregnant women) with confirmed EVD received two consecutive transfusions of 200 to 250 ml of ABO-compatible convalescent plasma, with each unit of plasma obtained from a separate convalescent donor. The transfusions were initiated on the day of diagnosis or up to 2 days later. The level of neutralizing antibodies against Ebola virus in the plasma was unknown at the time of administration. The control group was 418 patients who had been treated at the same center during the previous 5 months. The primary outcome was the risk of death during the period from 3 to 16 days after diagnosis with adjustments for age and the baseline cycle-threshold value on polymerase-chain-reaction assay; patients who had died before day 3 were excluded. The clinically important difference was defined as an absolute reduction in mortality of 20 percentage points in the convalescent-plasma group as compared with the control group. : A total of 84 patients who were treated with plasma were included in the primary analysis. At baseline, the convalescent-plasma group had slightly higher cycle-threshold values and a shorter duration of symptoms than did the control group, along with a higher frequency of eye redness and difficulty in swallowing. From day 3 to day 16 after diagnosis, the risk of death was 31% in the convalescent-plasma group and 38% in the control group (risk difference, -7 percentage points; 95% confidence interval [CI], -18 to 4). The difference was reduced after adjustment for age and cycle-threshold value (adjusted risk difference, -3 percentage points; 95% CI, -13 to 8). No serious adverse reactions associated with the use of convalescent plasma were observed. : The transfusion of up to 500 ml of convalescent plasma with unknown levels of neutralizing antibodies in 84 patients with confirmed EVD was not associated with a significant improvement in survival. (Funded by the European Union's Horizon 2020 Research and Innovation Program and others; ClinicalTrials.gov number, NCT02342171.).<br/

Modelling the B-DNA base pair opening reaction

Molecular modelling has been used to study the opening of the central base pair of a B- DNA oligonucleotide (dA)5.(dT)5. In our model, opening occurs by rotating the bases around an axis passing through the centre of the sugar connected to the opening base and oriented perpendicularly to the plane of the base. The results of this study show that the opening energies obtained for a single base pair are compatible with the activation energies deduced from hydrogen exchange experiments. Studies of possible opening pathways show that many possibilities exist although there is an overall preference for opening towards the major groove. In addition, we have demonstrated that a coupling exists between opening and DNA bending: bending the double helix facilitates base pair opening and, conversely, opening a base pair bends DNA and increases its local flexibility. Finally, based on the opening energetics obtained, we have carried out a Brownian dynamics study of the opening kinetics which again leads to results in good correlation with experimental findings and indicates that the base pair opening reaction is of a stochastic nature

A study of the human hair structure with a Zernike phase contrast X-ray microscope

We have observed the internal structure of human hair shafts with a transmission Zernike phase contrast hard X-ray microscope. Due to the high spatial resolution and the high contrast of the microscope, we could image scales, macrofibrils, medulla and melanin without staining. The structure of a black hair shaft is compared with that of a white one

A new deformation model of hard alpha-keratin fibers at the nanometer scale: implications for hard alpha-keratin intermediate filament mechanical properties.

The mechanical behavior of human hair fibers is determined by the interactions between keratin proteins structured into microfibrils (hard alpha-keratin intermediate filaments), a protein sulfur-rich matrix (intermediate filaments associated proteins), and water molecules. The structure of the microfibril-matrix assembly has already been fully characterized using electron microscopy and small-angle x-ray scattering on unstressed fibers. However, these results give only a static image of this assembly. To observe and characterize the deformation of the microfibrils and of the matrix, we have carried out time-resolved small-angle x-ray microdiffraction experiments on human hair fibers stretched at 45% relative humidity and in water. Three structural parameters were monitored and quantified: the 6.7-nm meridian arc, which is related to an axial separation between groups of molecules along the microfibrils, the microfibril's radius, and the packing distance between microfibrils. Using a surface lattice model of the microfibril, we have described its deformation as a combination of a sliding process and a molecular stretching process. The radial contraction of the matrix is also emphasized, reinforcing the hydrophilic gel nature hypothesis