Fluticasone propionate suppresses the SARS-CoV-2 induced increase in respiratory epithelial permeability in vitro.

BACKGROUND: Disruption of the nasal epithelial barrier is believed to play a role in Coronavirus Disease-2019 (COVID-19) outcomes. Fluticasone propionate has been shown to restore the nasal epithelial barrier in allergic rhinitis to the level of healthy controls. The therapeutic potential of nasal steroid sprays in COVID-19 has recently been reported. However, further insight into the mode of action is warranted. OBJECTIVES: To explore the in vitro mechanisms of the preventive potential of fluticasone propionate in SARS-CoV-2 infection. METHODS: Human air liquid interface cultures of Calu-3 cells and primary nasal epithelial cells isolated from healthy donors were used to investigate the preventive effect of fluticasone propionate on SARS-CoV-2 induced barrier disruption, virus replication and ACE2 expression. RESULTS: 48 hours pre-treatment with fluticasone propionate prevented the SARS-CoV-2 induced increase in fluorescein isothiocyanate-dextran 4 kDa permeability and reduced infection with SARS-CoV-2. Pre-treatment with fluticasone propionate also decreased ACE2 expression in SARS-CoV-2 infected Calu-3 cells. CONCLUSION: Fluticasone propionate pre-treatment prevented SARS-CoV-2 increased epithelial permeability, reduced ACE2 expression and SARS-CoV-2 infection, underscoring the therapeutic potential of fluticasone propionate in the context of COVID-19.

Probiotics for the airways: Potential to improve epithelial and immune homeostasis.

Probiotics are live microorganisms that, when administered in adequate amounts, confer health benefit on the host. The therapeutic effects of probiotics have been mostly studied in the gastrointestinal tract, but recent evidence points toward the potential of these bacteria to prevent and/or treat chronic airway diseases. In this review, possible mechanisms of action of probiotics in the airways are described, with a particular focus on their capacity to modulate the epithelial barrier function and their mode of interaction with the immune system. Indeed, probiotic bacteria, mostly lactobacilli, can promote the expression and regulation of tight junctions and adherence junctions, resulting in the restoration of a defective epithelial barrier. These bacteria interact with the epithelial barrier and immune cells through pattern recognition receptors, such as Toll-like receptors, which upon activation can stimulate or suppress various immune responses. Finally, the clinical potential of probiotics to treat inflammatory diseases of the upper and lower respiratory tract, and the difference between their mode of application (eg, oral or nasal) are discussed here.

European symposium on the awareness of allergy: report of the promotional campaign in the European Parliament (26-28 April 2016).

From 26 to 28 of April 2016, an allergy awareness campaign was organized by the European Academy of Allergy and Clinical Immunology and the European Federation of Allergy and Airway Diseases Patients Associations in the European Parliament in Brussels, with support of the European Parliament's Interest group on Allergy and Asthma and was co-hosted by the Members of the European Parliament David Borrelli, Sirpa Pietikainen and Nessa Childers. Skin prick tests (SPTs) were performed to gain attention for the increasing prevalence of allergic airway diseases in Europe. Since more than 30% of the total European population suffers from airway allergies and asthma, reaching a higher level of awareness and elaboration of an active prevention plan is mandatory. Of the 406 individuals undergoing SPT in the European Parliament, 211 participants (52%) reported to have suffered from an allergy in the past, with allergic symptoms being present in the nose and eyes (40% and 36%, respectively), the skin (27%), lower airways (14%) and the gut (8%). Of the 381 SPT with reliable results, cutaneous hypersensitivity was found in 201 (53%) participants. Of those with positive SPT (n = 201), 70 participants (35%) were monosensitized while 131 participants (65%) were polysensitized. The positive skin reactions were found mostly for grass pollen (n = 108), followed by Dermatophagoides pteronyssinus (n = 105), Dermatophagoides farina (n = 96) and birch pollen (n = 85). Of note, 54 individuals (14% of the total tested population) without reported allergy or allergic symptoms showed a positive SPT without clinical relevance. This report summarizes the main idea and goals of the symposium: chronic airway diseases are a major and growing health problem in Europe. Therefore, a joint preventive action plan needs to be developed for a better health status of European citizens.

EUFOREA Rhinology Research Forum 2016: report of the brainstorming sessions on needs and priorities in rhinitis and rhinosinusitis.

The first European Rhinology Research Forum organized by the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) was held in the Royal Academy of Medicine in Brussels on 17th and 18th November 2016, in collaboration with the European Rhinologic Society (ERS) and the Global Allergy and Asthma European Network (GA2LEN). One hundred and thirty participants (medical doctors from different specialties, researchers, as well as patients and industry representatives) from 27 countries took part in the multiple perspective discussions including brainstorming sessions on care pathways and research needs in rhinitis and rhinosinusitis. The debates started with an overview of the current state of the art, including weaknesses and strengths of the current practices, followed by the identification of essential research needs, thoroughly integrated in the context of Precision Medicine (PM), with personalized care, prediction of success of treatment, participation of the patient and prevention of disease as key principles for improving current clinical practices. This report provides a concise summary of the outcomes of the brainstorming sessions of the European Rhinology Research Forum 2016.

Field Effect and Strongly Localized Carriers in the Metal-Insulator Transition Material VO(2).

The intrinsic field effect, the change in surface conductance with an applied transverse electric field, of prototypal strongly correlated VO(2) has remained elusive. Here we report its measurement enabled by epitaxial VO(2) and atomic layer deposited high-κ dielectrics. Oxygen migration, joule heating, and the linked field-induced phase transition are precluded. The field effect can be understood in terms of field-induced carriers with densities up to ∼5×10(13) cm(-2) which are trongly localized, as shown by their low, thermally activated mobility (∼1×10(-3) cm(2)/V s at 300 K). These carriers show behavior consistent with that of Holstein polarons and strongly impact the (opto)electronics of VO(2).

Switching mechanism in two-terminal vanadium dioxide devices.

Two-terminal thin film VO2 devices show an abrupt decrease of resistance when the current or voltage applied exceeds a threshold value. This phenomenon is often described as a field-induced metal-insulator transition. We fabricate nano-scale devices with different electrode separations down to 100 nm and study how the dc switching voltage and current depend on device size and temperature. Our observations are consistent with a Joule heating mechanism governing the switching. Pulsed measurements show a switching time to the high resistance state of the order of one hundred nanoseconds, consistent with heat dissipation time. In spite of the Joule heating mechanism which is expected to induce device degradation, devices can be switched for more than 10(10) cycles making VO2 a promising material for nanoelectronic applications.

Search for bosonic superweakly interacting massive dark matter particles with the XMASS-I detector.

Bosonic superweakly interacting massive particles (super-WIMPs) are a candidate for warm dark matter. With the absorption of such a boson by a xenon atom, these dark matter candidates would deposit an energy equivalent to their rest mass in the detector. This is the first direct detection experiment exploring the vector super-WIMPs in the mass range between 40 and 120 keV. With the use of 165.9 day of data, no significant excess above background was observed in the fiducial mass of 41 kg. The present limit for the vector super-WIMPs excludes the possibility that such particles constitute all of dark matter. The absence of a signal also provides the most stringent direct constraint on the coupling constant of pseudoscalar super-WIMPs to electrons. The unprecedented sensitivity was achieved exploiting the low background at a level 10(-4) kg-1 keVee-1 day-1 in the detector.

Domain wall roughness in stripe phase BiFeO3 thin films.

Using the model system of ferroelectric domain walls, we explore the effects of long-range dipolar interactions and periodic ordering on the behavior of pinned elastic interfaces. In piezoresponse force microscopy studies of the characteristic roughening of intrinsic 71° stripe domains in BiFeO3 thin films, we find unexpectedly high values of the roughness exponent ζ=0.74±0.10, significantly different from those obtained for artificially written domain walls in this and other ferroelectric materials. The large value of the exponent suggests that a random field-dominated pinning, combined with stronger disorder and strain effects due to the step-bunching morphology of the samples, could be the dominant source of pinning in the system.

Body size and dispersal mode as key traits determining metacommunity structure of aquatic organisms.

Relationships between traits of organisms and the structure of their metacommunities have so far mainly been explored with meta-analyses. We compared metacommunities of a wide variety of aquatic organism groups (12 groups, ranging from bacteria to fish) in the same set of 99 ponds to minimise biases inherent to meta-analyses. In the category of passive dispersers, large-bodied groups showed stronger spatial patterning than small-bodied groups suggesting an increasing impact of dispersal limitation with increasing body size. Metacommunities of organisms with the ability to fly (i.e. insect groups) showed a weaker imprint of dispersal limitation than passive dispersers with similar body size. In contrast, dispersal movements of vertebrate groups (fish and amphibians) seemed to be mainly confined to local connectivity patterns. Our results reveal that body size and dispersal mode are important drivers of metacommunity structure and these traits should therefore be considered when developing a predictive framework for metacommunity dynamics.

Spin wave diffraction and perfect imaging of a grating.

We study the diffraction of Damon-Eshbach-type spin waves incident on a one-dimensional grating realized by microslits in a thin Permalloy film. By means of time-resolved scanning Kerr microscopy, we observe unique diffraction patterns behind the grating which exhibit replications of the spin wave field at the slits. We show that these spin wave images, with details finer than the wavelength of the incident Damon-Eshbach spin wavelength, arise from the strongly anisotropic spin wave dispersion.

Probability distributions for the run-and-tumble bacterial dynamics: an analogy to the Lorentz model.

In this paper, we exploit an analogy of the run-and-tumble process for bacterial motility with the Lorentz model of electron conduction in order to obtain analytical results for the intermediate scattering function. This allows to obtain an analytical result for the van Hove function in real space for two-dimensional systems. We furthermore consider the 2D circling motion of bacteria close to solid boundaries with tumbling, and show that the analogy to electron conduction in a magnetic field allows to predict the effective diffusion coefficient of the bacteria. The latter is shown to be reduced by the circling motion of the bacteria.

Search for differences in oscillation parameters for atmospheric neutrinos and antineutrinos at Super-Kamiokande.

We present a search for differences in the oscillations of antineutrinos and neutrinos in the Super-Kamiokande-I, -II, and -III atmospheric neutrino sample. Under a two-flavor disappearance model with separate mixing parameters between neutrinos and antineutrinos, we find no evidence for a difference in oscillation parameters. Best-fit antineutrino mixing is found to be at (Δm2,sin2 2θ)=(2.0×10(-3) eV2, 1.0) and is consistent with the overall Super-K measurement.

Exceptional cryptic diversity and multiple origins of parthenogenesis in a freshwater ostracod.

The persistence of asexual reproduction in many taxa depends on a balance between the origin of new asexual lineages and the extinction of old ones. This turnover determines the diversity of extant asexual populations and so influences the interaction between sexual and asexual modes of reproduction. Species with mixed reproduction, like the freshwater ostracod (Crustacea) morphospecies Eucypris virens, are a good model to examine these dynamics. This species is also a geographic parthenogen, in which sexual females and males co-exist with asexual females in the circum-Mediterranean area only, whereas asexual females occur all over Europe. A molecular phylogeny of E. virens based on the mitochondrial COI and 16S fragments is presented. It is characterised by many distinct clusters of haplotypes which are either exclusively sexual or asexual, with only one exception, and are often separated by deep branches. Analysis of the phylogeny reveals an astonishing cryptic diversity, which indicates the existence of a species complex with more than 40 cryptic taxa. We therefore suggest a revision of the single species status of E. virens. The phylogeny indicates multiple transitions from diverse sexual ancestor populations to asexuality. Although many transitions appear to be ancient, we argue that this may be an artefact of the existence of unsampled or extinct sexual lineages.

Direct phase probing and mapping via spintronic Michelson interferometry.

A spintronic approach is introduced to transform classic Michelson interferometry that probes the electromagnetic phase only. This method utilizes a nonlinear four-wave coherent mixing effect. A previously unknown striking relation between spin dynamics and the relative phase of electromagnetic waves is revealed. Spintronic Michelson interferometry allows direct probing of both the spin-resonance phase and the relative phase of electromagnetic waves via microspintronics. Thereby, it breaks new ground for cross-disciplinary applications with unprecedented capabilities, which we demonstrate via a powerful phase-resolved spin-resonance spectroscopy on magnetic materials and an on-chip technique for phase-resolved near-field microwave imaging.

Indications of proton-dominated cosmic-ray composition above 1.6 EeV.

We report studies of ultrahigh-energy cosmic-ray composition via analysis of depth of air shower maximum (X(max)), for air shower events collected by the High-Resolution Fly's Eye (HiRes) observatory. The HiRes data are consistent with a constant elongation rate d/d[log(E)] of 47.9+/-6.0(stat)+/-3.2(syst) g/cm2/decade for energies between 1.6 and 63 EeV, and are consistent with a predominantly protonic composition of cosmic rays when interpreted via the QGSJET01 and QGSJET-II high-energy hadronic interaction models. These measurements constrain models in which the galactic-to-extragalactic transition is the cause of the energy spectrum ankle at 4x10(18) eV.

Life sciences: microorganisms in the space environment.

Preliminary results of the Spacelab 1 experiment on the response of Bacillus subtilis spores to conditions of free space are presented. Exposure to the vacuum of space on the Spacelab pallet reduced viability counts about 50 percent and increased mutation frequencies by a factor of about 10. Interpretation of apparent differences in the photobiological and photochemical data between flight and ground simulation experiments will require more statistical analyses and data from actual fluence measurements.

Width of reaction zones in A+B-->C type reaction-diffusion processes: effects of an electric current.

We investigate the effects of an electric current on the width of a stationary reaction zone in an irreversible A(-)+B(+)-->C reaction-diffusion process. The ion dynamics of electrolytes A identical with (A(+),A(-)) and B identical with (B(+),B(-)) is described by reaction-diffusion equations obeying local electroneutrality and the stationary state is obtained by employing reservoirs of fixed electrolyte concentrations at the opposite ends of a finite domain. We find that the width of the reaction zone decreases when the current drives the reacting ions toward the reaction zone while it increases in the opposite case. The linear response of the width to the current is estimated by developing a phenomenological theory based on conservation laws and on electroneutrality. The theory is found to reproduce numerical solutions to a good accuracy.

Deletion of C2orf34, PREPL and SLC3A1 causes atypical hypotonia-cystinuria syndrome.

BACKGROUND: Hypotonia-cystinuria syndrome (HCS) and 2p21 deletion syndrome are two recessive contiguous gene deletion syndromes associated with cystinuria type I. The deletions differ in size and the number of genes involved. In HCS patients, only SLC3A1 and PREPL are disrupted. In the 2p21 deletion syndrome, two additional genes (C2orf34 and PPM1B) are lost. OBJECTIVE: Clinical and molecular analysis of two siblings who presented with an atypical HCS phenotype. METHODS: Molecular analysis of the SLC3A1/PREPL locus was performed in the patients using quantitative polymerase chain reaction (PCR) methods. RESULTS: HCS in both siblings was confirmed with the deletion screen of the SLC3A1/PREPL locus. Fine mapping of the breakpoint revealed a deletion of 77.4 kb, including three genes: SLC3A1, PREPL and C2orf34. Features not present in classical HCS were a mild/moderate mental retardation and a respiratory chain complex IV deficiency documented in patient 2. CONCLUSIONS: We report the first patients with a deletion of SLC3A1, PREPL and C2orf34. They present with a phenotype intermediate between HCS and 2p21 deletion syndrome. These patients facilitate the elucidation of the contribution of each gene to the phenotype in the different 2p21 deletion syndromes.

Guiding fields for phase separation: controlling Liesegang patterns.

Liesegang patterns emerge from precipitation processes and may be used to build bulk structures at submicrometer length scales. Thus they have significant potential for technological applications provided adequate methods of control can be devised. Here we describe a simple, physically realizable pattern control based on the notion of driven precipitation, meaning that the phase separation is governed by a guiding field such as, for example, a temperature or pH field. The phase separation is modeled through a nonautonomous Cahn-Hilliard equation whose spinodal is determined by the evolving guiding field. Control over the dynamics of the spinodal gives control over the velocity of the instability front that separates the stable and unstable regions of the system. Since the wavelength of the pattern is largely determined by this velocity, the distance between successive precipitation bands becomes controllable. We demonstrate the above ideas by numerical studies of a one-dimensional system with a diffusive guiding field. We find that the results can be accurately described by employing a linear stability analysis (pulled-front theory) for determining the velocity-local-wavelength relationship. From the perspective of the Liesegang theory, our results indicate that the so-called revert patterns may be naturally generated by diffusive guiding fields.

Aortoesophageal fistula following endovascular exclusion of a thoracic aneurysm.

The aim of this study was to report a case of aortoesophageal fistula following endovascular exclusion of a thoracic aneurysm, treated conservatively with fatal outcome. Endovascular exclusion of a thoracic aneurysm was performed in a 64-year-old female patient. Three months later the diagnosis of an aortoesophageal fistula was made and minimal surgery (cervicotomy and jejunostomy) was performed, combined with antibiotherapy and catheter flushing of the infected excluded aneurysm thrombus. The patient died in septic shock 9 weeks later. As reported, following conventional thoracic aortic aneurysm surgery, endovascular stenting of the thoracic aorta can be complicated by aortoesophageal fistula. Management should be surgical, since the outcome under conservative management seems invariably fatal. However, it looks as if the poor condition of these patients may not permit open surgical treatment.