Divergent dynamics of inflammatory mediators and multiplex PCRs during airway infection in cystic fibrosis patients and healthy controls: Serial upper airway sampling by nasal lavage.

Background: In cystic fibrosis (CF), acute respiratory exacerbations critically enhance pulmonary destruction. Since these mainly occur outside regular appointments, they remain unexplored. We previously elaborated a protocol for home-based upper airway (UAW) sampling obtaining nasal-lavage fluid (NLF), which, in contrast to sputum, does not require immediate processing. The aim of this study was to compare UAW inflammation and pathogen colonization during stable phases and exacerbations in CF patients and healthy controls. Methods: Initially, we obtained NLF by rinsing 10 ml of isotonic saline/nostril during stable phases. During exacerbations, subjects regularly collected NLF at home. CF patients directly submitted one aliquot for microbiological cultures. The remaining samples were immediately frozen until transfer on ice to our clinic, where PCR analyses were performed and interleukin (IL)-1ß/IL-6/IL-8, neutrophil elastase (NE), matrix metalloproteinase (MMP)-9, and tissue inhibitor of metalloproteinase (TIMP)-1 were assessed. Results: Altogether, 49 CF patients and 38 healthy controls (HCs) completed the study, and 214 NLF samples were analyzed. Of the 49 CF patients, 20 were at least intermittently colonized with P. aeruginosa and received azithromycin and/or inhaled antibiotics as standard therapy. At baseline, IL-6 and IL-8 tended to be elevated in CF compared to controls. During infection, inflammatory mediators increased in both cohorts, reaching significance only for IL-6 in controls (p=0.047). Inflammatory responses tended to be higher in controls [1.6-fold (NE) to 4.4-fold (MMP-9)], while in CF, mediators increased only moderately [1.2-1.5-fold (IL-6/IL-8/NE/TIMP-1/MMP-9)]. Patients receiving inhalative antibiotics or azithromycin (n=20 and n=15, respectively) revealed lower levels of IL-1ß/IL-6/IL-8 and NE during exacerbation compared to CF patients not receiving those antibiotics. In addition, CF patients receiving azithromycin showed MMP-9 levels significantly lower than CF patients not receiving azithromycin at stable phase and exacerbation. Altogether, rhinoviruses were the most frequently detected virus, detected at least once in n=24 (49.0%) of the 49 included pwCF and in n=26 (68.4%) of the 38 healthy controls over the 13-month duration of the study. Remarkably, during exacerbation, rhinovirus detection rates were significantly higher in the HC group compared to those in CF patients (65.8% vs. 22.4%; p<0.0001). Conclusion: Non-invasive and partially home-based UAW sampling opens new windows for the assessment of inflammation and pathogen colonization in the unified airway system.

Large T g Shift in Hybrid Bragg Stacks through Interfacial Slowdown.

Studies of glass transition under confinement frequently employ supported polymer thin films, which are known to exhibit different transition temperature T g close to and far from the interface. Various techniques can selectively probe interfaces, however, often at the expense of sample designs very specific to a single experiment. Here, we show how to translate results on confined thin film T g to a "nacre-mimetic" clay/polymer Bragg stack, where periodicity allows to limit and tune the number of polymer layers to either one or two. Exceptional lattice coherence multiplies signal manifold, allowing for interface studies with both standard T g and broadband dynamic measurements. For the monolayer, we not only observe a dramatic increase in T g (∼ 100 K) but also use X-ray photon correlation spectroscopy (XPCS) to probe platelet dynamics, originating from interfacial slowdown. This is confirmed from the bilayer, which comprises both "bulk-like" and clay/polymer interface contributions, as manifested in two distinct T g processes. Because the platelet dynamics of monolayers and bilayers are similar, while the segmental dynamics of the latter are found to be much faster, we conclude that XPCS is sensitive to the clay/polymer interface. Thus, large T g shifts can be engineered and studied once lattice spacing approaches interfacial layer dimensions.

Anisotropic Thermal Transport in Spray-Coated Single-Phase Two-Dimensional Materials: Synthetic Clay Versus Graphene Oxide.

Directional control on material properties such as mechanical moduli or thermal conductivity are of paramount importance for the development of nanostructured next-generation devices. Two-dimensional materials are particularly interesting in this context owing to their inherent structural anisotropy. Here, we compare graphene oxide (GO) and synthetic clay sodium fluorohectorite (Hec) with respect to their thermal transport properties. The unique sheet structure of both allows preparation of highly ordered Bragg stacks of these pure materials. The thermal conductivity parallel to the platelets strongly exceeds that perpendicular to them. We find a significant difference in the performance between GO and synthetic clay. Our analysis of the textured structure, size of the platelets, and chemical composition shows that Hec is a superior two-dimensional component to GO. Consequently, synthetic clay is a promising material for thermal management applications in electronic devices where electrically insulating materials are prerequisites.

Tunable Thermoelastic Anisotropy in Hybrid Bragg Stacks with Extreme Polymer Confinement.

Controlling thermomechanical anisotropy is important for emerging heat management applications such as thermal interface and electronic packaging materials. Whereas many studies report on thermal transport in anisotropic nanocomposite materials, a fundamental understanding of the interplay between mechanical and thermal properties is missing, due to the lack of measurements of direction-dependent mechanical properties. In this work, exceptionally coherent and transparent hybrid Bragg stacks made of strictly alternating mica-type nanosheets (synthetic hectorite) and polymer layers (polyvinylpyrrolidone) were fabricated at large scale. Distinct from ordinary nanocomposites, these stacks display long-range periodicity, which is tunable down to angstrom precision. A large thermal transport anisotropy (up to 38) is consequently observed, with the high in-plane thermal conductivity (up to 5.7 W m-1 K-1 ) exhibiting an effective medium behavior. The unique hybrid material combined with advanced characterization techniques allows correlating the full elastic tensors to the direction-dependent thermal conductivities. We, therefore, provide a first analysis on how the direction-dependent Young's and shear moduli influence the flow of heat.