Dimethyl fumarate modulates the regulatory T cell response in the mesenteric lymph nodes of mice with experimental autoimmune encephalomyelitis.

Dimethyl fumarate (DMF, Tecfidera) is an oral drug utilized to treat relapsing-remitting multiple sclerosis (MS). DMF treatment reduces disease activity in MS. Gastrointestinal discomfort is a common adverse effect of the treatment with DMF. This study aimed to investigate the effect of DMF administration in the gut draining lymph nodes cells of C57BL6/J female mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We have demonstrated that the treatment with DMF (7.5 mg/kg) significantly reduces the severity of EAE. This reduction of the severity is accompanied by the increase of both proinflammatory and anti-inflammatory mechanisms at the beginning of the treatment. As the treatment progressed, we observed an increasing number of regulatory Foxp3 negative CD4 T cells (Tr1), and anti-inflammatory cytokines such as IL-27, as well as the reduction of PGE2 level in the mesenteric lymph nodes of mice with EAE. We provide evidence that DMF induces a gradual anti-inflammatory response in the gut draining lymph nodes, which might contribute to the reduction of both intestinal discomfort and the inflammatory response of EAE. These findings indicate that the gut is the first microenvironment of action of DMF, which may contribute to its effects of reducing disease severity in MS patients.

Simulation of the Attrition of Recycled Concrete Aggregates during Concrete Mixing.

Concrete mixing can lead to mechanical degradation of aggregates, particularly when dealing with recycled concrete aggregates. In this work, the attrition of such materials during mixing is studied by means of experiments and simulations. The effect of the presence of fines, water addition, flow configuration of the mixer (co- or counter-current) and impeller frequency is discussed. Experiments were performed in a laboratory Eirich mixer. Discrete element numerical simulations (DEM) were performed on the same geometry by mimicking the behaviour of the material and, in particular, the cohesion induced by water and the cement paste using either Hertz-Mindlin or Hertz-Mindlin with Johnson-Kendall-Roberts (JKR) contact laws. The combination of the collision energy spectra extracted from the DEM simulations and an attrition model allowed the prediction of the mass loss due to attrition in 1-min experiments. Semi-quantitative agreement was observed between experiments and simulations, with a mean relative error of 26.4%. These showed that higher mass losses resulted from operation at the highest impeller speeds, co-current operation, and also with the wet aggregate. Mixing of the agglomerate in the concrete mix resulted in a significant reduction in attrition when compared to mixing aggregates alone. With further validation, the proposed simulation approach can become a valuable tool in the optimization of mixing by allowing the effects of material, machine and process variables to be studied on the mass loss due to attrition.