Neuromyelitis optica spectrum disorder after treatment with pembrolizumab.

While immune checkpoint inhibitors (ICIs) have contributed to the development of therapeutic treatments for previously incurable advanced malignancies, they may induce immune-related adverse events (irAEs) in many organs including the CNS [1]. Because immune checkpoint molecules are predominantly expressed on T cells, irAEs are largely not B cell-mediated. Here, we report a patient who was treated with pembrolizumab (a PD-1 monoclonal antibody) for lung adenocarcinoma with brain metastasis, and who developed anti-aquaporin-4 antibody (AQP4-Ab) positive neuromyelitis optica spectrum disorder (NMOSD). We hypothesized that PD-1 immune checkpoint blockage might induce a B cell-mediated immune response in CNS resulting in this complication, which was further supported by the observation of a transient increase in plasmablasts in their CSF.

Structural and biochemical characterisation of a novel alginate lyase from Paenibacillus sp. str. FPU-7.

A novel alginate lyase, PsAly, with a molecular mass of 33 kDa and whose amino acid sequence shares no significant similarity to other known proteins, was biochemically and structurally characterised from Paenibacillus sp. str. FPU-7. The maximum PsAly activity was obtained at 65 °C, with an optimum pH of pH 7-7.5. The activity was enhanced by divalent cations, such as Mg2+, Mn2+, or Co2+, and inhibited by a metal chelator, ethylenediaminetetraacetic acid. The reaction products indicated that PsAly is an endolytic enzyme with a preference for polymannuronate. Herein, we report a detailed crystal structure of PsAly at a resolution of 0.89 Å, which possesses a ß-helix fold that creates a long cleft. The catalytic site was different from that of other polysaccharide lyases. Site-directed mutational analysis of conserved residues predicted Tyr184 and Lys221 as catalytic residues, abstracting from the C5 proton and providing a proton to the glycoside bond, respectively. One cation was found to bind to the bottom of the cleft and neutralise the carboxy group of the substrate, decreasing the pKa of the C5 proton to promote catalysis. Our study provides an insight into the structural basis for the catalysis of alginate lyases and ß-helix polysaccharide lyases.

Influence of group training frequency on arterial stiffness in elderly women.

We evaluated the effects of different training frequencies on arterial stiffness. 77 elderly women (mean 68.8 years and 7.0 SD) were divided into two training (1DW and 2DW) and a CONTROL group (n = 23). 1DW (n = 29) participated in 90-min group training once a week for 12 weeks, while 2DW (n = 25) attended twice a week. Each training program included recreational activities, six to eight resistance exercises for circuit training, and leg exercises for chair-based exercise. Brachial systolic and diastolic blood pressures and the brachial-to-ankle pulse-wave velocity (baPWV) were obtained in the supine position. Muscle strength and ventilatory threshold were also measured. After the training program, a reduction (P < 0.01) in baPWV was observed in 2DW (-7.8 +/- 7.0%) but not in 1DW (-1.5 +/- 7.5%) and CONTROL (-0.4 +/- 7.5%) without any changes in other measurements. The results suggest that, in order to improve arterial stiffness, an exercise frequency of at least twice a week is to be recommended for elderly.