Inflammation across tissues: can shared cell biology help design smarter trials?

Immune-mediated inflammatory diseases (IMIDs) are responsible for substantial global disease burden and associated health-care costs. Traditional models of research and service delivery silo their management within organ-based medical disciplines. Very often patients with disease in one organ have comorbid involvement in another, suggesting shared pathogenic pathways. Moreover, different IMIDs are often treated with the same drugs (including glucocorticoids, immunoregulators and biologics). Unlocking the cellular basis of these diseases remains a major challenge, leading us to ask why, if these diseases have so much in common, they are not investigated in a common manner. A tissue-based, cellular understanding of inflammation might pave the way for cross-disease, cross-discipline basket trials (testing one drug across two or more diseases) to reduce the risk of failure of early-phase drug development in IMIDs. This new approach will enable rapid assessment of the efficacy of new therapeutic agents in cross-disease translational research in humans.

Bottom-Up Synthesis of De-Functionalized and Dispersible Carbon Spheres as Colloidal Adsorbent.

Recent innovative adsorption technologies for water purification rely on micrometer-sized activated carbon (AC) for ultrafast adsorption or in situ remediation. In this study, the bottom-up synthesis of tailored activated carbon spheres (aCS) from sucrose as renewable feedstock is demonstrated. The synthesis is based on a hydrothermal carbonization step followed by a targeted thermal activation of the raw material. This preserves its excellent colloid properties, i.e., narrow particle size distribution around 1 µm, ideal spherical shape and excellent aqueous dispersibility. We investigated the ageing of the freshly synthesized, highly de-functionalized AC surface in air and aqueous media under conditions relevant to the practice. A slow but significant ageing due to hydrolysis and oxidation reactions was observed for all carbon samples, leading to an increase of the oxygen contents with storage time. In this study, a tailored aCS product was generated within a single pyrolysis step with 3 vol.-% H2O in N2 in order to obtain the desired pore diameters and surface properties. Adsorption characteristics, including sorption isotherms and kinetics, were investigated with monochlorobenzene (MCB) and perfluorooctanoic acid (PFOA) as adsorbates. The product showed high sorption affinities up to log (KD/[L/kg]) of 7.3 ± 0.1 for MCB and 6.2 ± 0.1 for PFOA, respectively.

Functionalization of porous siliceous materials, Part 2: Surface characterization by inverse gas chromatography.

Surface modification of porous glass beads by ethanol-based 3-mercaptopropyltrimethoxysilane (MPTMS) grafting solutions is directly evidenced by nitrogen adsorption, elemental analysis, thermogravimetry, infrared and 29Si CP MAS NMR spectroscopy. Furthermore, the energetic characterization of the surface is essential to understand comprehensively the physico-chemical interactions between the pristine and MPTMS-modified surface and its gas/liquid-phase environment. In this study, inverse gas chromatography (IGC) is used to characterize the surface properties of porous glass (PG). By means of IGC at infinite dilution (IGC-ID), the dispersive component of the surface energy (γsd), the enthalpy and entropy of adsorption of C6-C10 hydrocarbon probes were determined at temperatures between 30 and 120 °C. The specific component of the surface energy (γssp) at the temperature of 120 °C has been obtained via the Van Oss theory and a least-squares procedure evaluating the IGC data of 8 polar probe molecules collectively. After surface silylation, the total surface energy (γst) decreased from 402 to 255 mJ/m² indicating both a reduced wettability and an increased hydrophobicity of the MPTMS-modified PG. Moreover, the acidity/basicity parameters according to the Van Oss and the Gutmann approach indicated that the acidity of the PG surface decreases by MPTMS grafting. Using n-octane and isopropanol probes, IGC at finite concentration (IGC-FC) was applied to obtain their adsorption isotherms and subsequently the BET specific surface areas. In addition, the surface heterogeneity of the studied PGs was also computed. The energy distribution functions of adsorption sites were monomodal (peak maximum at about 22 kJ/mol) for the n-octane probe, while isopropanol revealed a bimodal distribution function (maxima at about 18 and 25 kJ/mol) on both pristine and MPTMS-modified PG. Furthermore, the proportion of high energy sites (apparently assigned to SiOH groups) has been reduced by surface modification from 65% to only 35% despite a high surface coverage of ˜10 MPTMS species/nm2. These findings are in agreement with the results of 29Si CP MAS NMR measurements and are supported by DFT calculations on the adsorption of isopropanol and n-octane on the surface of a silica cluster model.

Silica monoliths with hierarchical porosity obtained from porous glasses.

This review deals with "classical" porous glasses which are prepared by physical phase separation of alkali borosilicate glasses of suitable composition in combination with selective leaching. The resulting materials are characterized by a controllable pore size in the nanometer range, high mechanical, thermal and chemical stability and an adjustable macroscopic shape, which enables manufacturing of glass monoliths with various geometries. As a result of their formation, porous glasses obtained from physical phase separation exhibit a monomodal pore structure. There are only a few examples in the literature for the synthesis of hierarchically porous glasses. This review covers several synthesis strategies for the introduction of hierarchy into "classical" porous glass monoliths, including sintering and fusion of alkali borosilicate initial glasses as well as partial or complete pseudomorphic transformation of porous glasses into zeolites or ordered mesoporous materials.

Dimenhydrinate in children with infectious gastroenteritis: a prospective, RCT.

OBJECTIVE: Vomiting is a common symptom in children with infectious gastroenteritis. It contributes to fluid loss and is a limiting factor for oral rehydration therapy. Dimenhydrinate has traditionally been used for children with gastroenteritis in countries such as Canada and Germany. We investigated the efficacy and safety of dimenhydrinate in children with acute gastroenteritis. METHODS: We performed a prospective, randomized, placebo-controlled, multicenter trial. We randomly assigned 243 children with presumed gastroenteritis and vomiting to rectal dimenhydrinate or placebo. Children with no or mild dehydration were included. All children received oral rehydration therapy. Primary outcome was defined as weight gain within 18 to 24 hours after randomization. Secondary outcomes were number of vomiting episodes, fluid intake, parents' assessment of well-being, number of diarrheal episodes, and admission rate to hospital. We recorded potential adverse effects. RESULTS: Change of weight did not differ between children who received dimenhydrinate or placebo. The mean number of vomiting episodes between randomization and follow-up visit was 0.64 in the dimenhydrinate group and 1.36 in the placebo group. In total, 69.6% of the children in the dimenhydrinate group versus 47.4% in the placebo group were free of vomiting between randomization and the follow-up visit. Hospital admission rate, fluid intake, general well-being of the children, and potential adverse effects, including the number of diarrhea episodes, were similar in both groups. CONCLUSIONS: Dimenhydrinate reduces the frequency of vomiting in children with mild dehydration; however, the overall benefit is low, because it does not improve oral rehydration and clinical outcome.