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.

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.

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.

Cognitive Function in Parkinson's Disease Patients with and without Anxiety.

Research on the implications of anxiety in Parkinson's disease (PD) has been neglected despite its prevalence in nearly 50% of patients and its negative impact on quality of life. Previous reports have noted that neuropsychiatric symptoms impair cognitive performance in PD patients; however, to date, no study has directly compared PD patients with and without anxiety to examine the impact of anxiety on cognitive impairments in PD. This study compared cognitive performance across 50 PD participants with and without anxiety (17 PDA+; 33 PDA-), who underwent neurological and neuropsychological assessment. Group performance was compared across the following cognitive domains: simple attention/visuomotor processing speed, executive function (e.g., set-shifting), working memory, language, and memory/new verbal learning. Results showed that PDA+ performed significantly worse on the Digit Span forward and backward test and Part B of the Trail Making Task (TMT-B) compared to the PDA- group. There were no group differences in verbal fluency, logical memory, or TMT-A performance. In conclusion, anxiety in PD has a measurable impact on working memory and attentional set-shifting.

Anxiety is associated with freezing of gait and attentional set-shifting in Parkinson's disease: A new perspective for early intervention.

Previous research has shown that anxiety in Parkinson's disease (PD) is associated with freezing of gait (FOG), and may even contribute to the underlying mechanism. However, limited research has investigated whether PD patients with FOG (PD+FOG) have higher anxiety levels when compared directly to non-freezing PD patients (PD-NF) and moreover, how anxiety might contribute to FOG. The current study evaluated whether: (i) PD+FOG have greater anxiety compared to PD-NF, and (ii) anxiety in PD is related to attentional set-shifting, in order to better understand how anxiety might be contributing to FOG. In addition, we explored whether anxiety levels differed between those PD patients with mild FOG (PD+MildFOG) compared to PD-NF. Four hundred and sixty-one patients with PD (231 PD-NF, 180 PD+FOG, 50 PD+MildFOG) were assessed using the Freezing of Gait Questionnaire item 3 (FOG-Q3), Hospital Anxiety and Depression Scale (HADS), Digit Span Test, Logical Memory Retention Test and Trail Making Tests. Compared to PD-NF, PD+FOG had significantly greater anxiety (p<0.001). PD+MildFOG, however, demonstrated similar levels of anxiety as the PD+FOG. In all patients, the severity of anxiety symptoms was significantly correlated to their degree of self-reported FOG on FOG-Q3 (p<0.001) and TMT B-A (p=0.039). Similar results were found for depression. In conclusion, these results confirm the key role played by anxiety in FOG and also suggest that anxiety might be a promising biomarker for FOG. Future research should consider whether treating anxiety with pharmacological and/or cognitive behavioural therapies at early stages of gait impairment in PD may alleviate troublesome FOG.

The role of the medial prefrontal cortex in updating reward value and avoiding perseveration.

The medial prefrontal cortex (mPFC) plays a major role in goal-directed behaviours, but it is unclear whether it plays a role in breaking away from a high-value reward in order to explore for better options. To address this question, we designed a novel 3-arm Bandit Task in which rats were required to choose one of three potential reward arms, each of which was associated with a different amount of food reward and time-out punishment. After a variable number of choice trials the reward locations were shuffled and animals had to disengage from the now devalued arm and explore the other options in order to optimise payout. Lesion and control groups' behaviours on the task were then analysed by fitting data with a reinforcement learning model. As expected, lesioned animals obtained less reward overall due to an inability to flexibly adapt their behaviours after a change in reward location. However, modelling results showed that lesioned animals were no more likely to explore than control animals. We also discovered that all animals showed a strong preference for certain maze arms, at the expense of reward. This tendency was exacerbated in the lesioned animals, with the strongest effects seen in a subset of animals with damage to dorsal mPFC. The results confirm a role for mPFC in goal-directed behaviours but suggest that rats rely on other areas to resolve the explore-exploit dilemma.

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).

Body composition and plasma lipid and stress hormone levels during 3 weeks of feed restriction and refeeding in low birth weight female pigs.

Compensatory growth in response to feed restriction (FR) affects deposition rates of lean and adipose tissues. It is, however, unclear whether pigs with low birth weight differ from their counterparts with normal birth weight with regard to compensatory growth. Female littermate pigs with low (UW; 1.1 kg) and normal (NW; 1.5 kg) birth weight were fed to appetite (control, CON) or feed restricted (RES) at 60% of DMI of the CON group between 78 and 98 d of age and subsequently refed at the level of the CON group until 131 d of age. Subgroups of pigs were slaughtered at 75, 98, 104, and 131 d of age to compare BW and body composition. Blood samples were taken at 98 and 119 d of age to analyze plasma metabolites and hormones. At birth UW pigs were shorter and had lower BW until 131 d of age than NW pigs ( < 0.05). Feed intake per kilogram of BW was greater in UW than in NW pigs ( < 0.01). The UW and NW pigs differed in carcass composition as indicated by greater relative subcutaneous fat at 75 d ( < 0.1), greater shoulder back fat ( < 0.05) at 98 d, and lower carcass weight at 131 d with greater abdominal and subcutaneous neck back fat in UW compared with NW pigs ( < 0.05). During FR, BW gain of RES pigs was lower than in NW pigs. The RES pigs showed greater feed intake after termination of FR until 131 d than CON pigs ( < 0.01). At 98 d RES pigs were leaner than CON pigs ( < 0.05). After 6 d of refeeding (104 d) relative fat depot weights were still smaller ( < 0.03) in RES pigs than in CON pigs. After 5 wk of refeeding, RES pigs had lower abdominal fat weights and greater plasma cortisol levels than CON pigs ( < 0.05). Regarding the plasma metabolite and hormone response, at 98-d fasting levels of plasma NEFA and glycerol were greater in RES than in CON pigs ( < 0.05), and after the drop in their levels after morning feeding ( < 0.001), plasma NEFA and glycerol and also triacylglycerol increased until the next meal in RES vs. CON pigs ( < 0.01). Plasma cortisol was greater in RES pigs after 3-wk FR ( < 0.05), whereas only a trend for increased plasma adrenalin concentrations in RES pigs at the end of the FR period and after 5 wk of refeeding was found ( < 0.1). In conclusion, UW pigs at 75 d of age (20 to 23 kg BW) had greater subcutaneous fat, whereas at 131 d (61 to 68 kg BW) they showed greater abdominal fat than NW pigs, suggesting that subcutaneous fat is deposited earlier than abdominal fat. The FR caused similar changes in body composition, plasma lipids, and stress hormones in UW and NW pigs.

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.

A closer look at mechanisms underlying perceptual differences in Parkinson's freezers and non-freezers.

Parkinson's disease patients who suffer from freezing of gait (PD-FOG) may have sensory and/or perceptual deficits, although they are difficult to disentangle. This study evaluated whether visuospatial perception or self-motion perception were more impaired in PD-FOG, and whether distance estimation errors might be related to misperception of physical walking (compared to imagined). Finally, cognitive status was evaluated in order to evaluate whether cognitive status predicts any of the perception deficits identified. Nine PD-FOG and 15 PD-nonFOG were tested. In experiment 1, participants were shown a target, then the target was removed, before participants demonstrated the original position of the target in two different feedback conditions (pointing with a laser, or walking to its original position). In experiment 2, participants walked to a target (3, 4.5, 6m) and then imagined walking to that same target. The time to complete both of these tasks was measured and compared. Experiment 1 found a significantly greater judgment error in PD-FOG across both conditions (p=0.013) (compared to PD-nonFOG). Constant error revealed that both groups significantly underestimated during the self-motion condition only (p=0.01). Interestingly, results from experiment 2 demonstrated a significant discrepancy between the time it took to imagine walking compared to their actual movement times, specifically in PD-FOG (p=0.03). This mismatch as well as cognitive status significantly predicted judgment errors during the self-motion condition from experiment 1. Therefore, this study found evidence that PD-FOG have significantly greater sensory-perception deficits compared to PD-nonFOG. These findings have important clinical implications for further understanding FOG and developing new rehabilitative strategies for FOG symptoms.

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.

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.

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.

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.

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.