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CD19-CAR T-cell therapy (CART19) causes B-cell aplasia (BCA) and dysgammaglobulinemia but there is a lack of information about the degree of its secondary immunodeficiency. We conducted a prospective study in children and young adults with acute lymphoblastic leukaemia treated with CART19, analysing the kinetics of BCA and dysgammaglobulinemia during therapy, as well as the B-cell reconstitution in those with CART19 loss. Thirty-four patients were included (14 female) with a median age at CART19 infusion of 8.7 years (2.9–24.9). Median follow-up after infusion was 7.1 months (0.5–42). BCA was observed 7 days after infusion (3–8), with persistence at 24 months in 60% of patients. All patients developed a progressive decrease in IgM and IgA: 71% had undetectable IgM levels at 71 days (41–99) and 13% undetectable IgA levels at 185 days (11–308). Three of 12 patients had protective levels of IgA in saliva. In two of three patients who lost CART19, persistent B-cell dysfunction was observed. No severe infections occurred. In conclusion, BCA occurs soon after CART19 infusion, with a progressive decrease in IgM and IgA, and with less impairment of IgA, suggesting the possibility of an immune reservoir. A persistent B-cell dysfunction might persist after CART19 loss in this population.

A combination of experimental (quasi-elastic neutron scattering and 2H NMR) and computational (molecular dynamics) tools was used to uncover the molecular mobility of benzene trapped inside the flexible channel-type MIL-53 (Cr3+) MOF. This material was shown to undergo a contraction of the structure upon benzene adsorption with the formation of a narrow pore phase with a smaller aperture. This confinement was found to strongly influence the dynamics of the guest: benzene diffuses in a region centered in the middle of the pore by a 1D-jump translational mechanism along the tunnel ruled by the presence of the μ2-OH groups present at the MOF pore wall. This translational diffusion is combined with a fast uniaxial rotational motion around the C6-axis. Any other rotational motion that involves the tumbling of the phenyl rings about the channel axis is much less probable due to a high activation energy barrier (49 kJ mol–1). In this way benzene can be pictured as a rotating disc that diffuses rapidly through the central part of the channel by short jumps between neighboring low energy basins located in the vicinity of the μ2-OH groups of the MIL-53 channels.

The dynamics of xylene isomers in the metal–organic framework MIL-47(V) has been investigated by combining molecular dynamics (MD) simulations and experimental tools including quasi-elastic neutron scattering (QENS) and deuterium nuclear magnetic resonance (2H NMR).The experimental and simulated self-diffusion coefficients (Ds) values for each single component isomer are in reasonable agreement in the whole range of temperatures. More interestingly, the simulations predict a nonmonotonous evolution of Dswith the temperature for all xylenes. Such an unusual trend is experimentally confirmed for p-xylene. Two distinct diffusion regimes are elucidated at the microscopic level: a low-temperature regime where the xylene molecules are close to the MIL-47(V) pore wall with a high activation energy barrier for the diffusion and a high-temperature regime where the xylene molecules are mainly located in the center of the channel associated with a lower activation energy for the diffusion. This dynamic behavior remains also true whatever the degree of pore filling. It has been further shown that the diffusivity is only slightly affected when one compares the case of xylenes in single component and in mixture. 2H NMR experiments enlighten that packing effects and guest–guest interactions are crucial when considering the dynamics of confined xylenes in MIL-47(V).

The adsorption properties of linear long chain alkanes (from n-pentane to n-nonane) within the rigid MOF MIL-47 (V) have been explored by combining gravimetry measurements and molecular simulations. Both experimental absolute isotherms and enthalpies of adsorption for all n-alkanes were compared with those obtained by configurational bias grand canonical Monte Carlo simulations (CB-GCMC) based on two different force fields. From a fair agreement between experimental and simulated data, a further step consisted of investigating the microscopic adsorption mechanism in play to shed some light onto the preferential orientations and conformations of all investigated n-alkanes. Whereas the trans conformation is predominantly observed for all n-alkanes, the proportion of the n-alkane conformations lying parallel to the direction of the tunnel significantly increases with the chain length, emphasizing that the confinement effect is stronger for the longer chain n-alkanes. Finally, molecular dynamics simulations allowed us to emphasize that all n-alkanes follow a pathway along the direction of the tunnel, leading to a 1D type diffusion mechanism, the motions being mainly centered around the middle of the pores at low loading, whereas they are significantly shifted toward the pore wall when the alkane concentration increases.

40 girls and 12 boys with CH. (8 athyreosis, 33 ectopics, 11 anatomically normal gland) whose treatment began at day : 29 ± 12 (mean ± SD) were followed for at least 4 years and in 13 cases for 7 years. The results of the Brunet-Lezine test at 0.5, 1, and 2 years; the Termann-Merill at 4 years and the WICSR test at 7 years, were all within the normal range but with a wide scatter : range 85-145 at 4 years, 95-133 at 7 years. The factors involved in this scatter were investigated.The following factors had no influence : clinical evidence of hypothyroidism at diagnosis, the presence and duration of neonatal jaundice, the initial levels of T4 and TSH, the etiology after 2 years, the date of starting treatment provided that this occured within the 2 first months of life.The following factors had a positive influence on the outcome : the presence of the 2 epiphysis of the knee (p <.025), socioeconomic level of parents (Graffar) : high medium vs medium (p <.05), vs low medium (p < .005) and good hormonal control during the first year (p <.025) and the following years (p<.05). The presence of psychological problems were predictive of a comparatively poor outcome : mild problems (p<.005) and severe problems (p <.0005) mild vs severe (p <.05). The development of psychological problems are associated with an initial hospitalization (p < .001) and the duration of it (p < .025).Postnatal factors are predominant which emphasises the need for good medical and familial care.