Mediators and Cytokines in Persistent Allergic Rhinitis and Nonallergic Rhinitis with Eosinophilia Syndrome

Background: Patients with nonallergic rhinitis with eosinophilia syndrome (NARES) show typical symptoms of persistent allergic rhinitis (PAR). The aim of the present study was to compare nasal cytokine patterns between NARES and PAR. Methods: Nasal secretions of 31 patients suffering from NARES, 20 patients with PAR to house dust mite and 21 healthy controls were collected using the cotton wool method and analyzed for interleukin (IL)-1 beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 beta (MIP-1 beta) by Bio-Plex Cytokine Assay as well as eosinophil cationic protein (ECP) and tryptase by UniCAP-FEIA. Results: NARES and PAR presented elevated levels of tryptase, while ECP was markedly increased solely in NARES compared to both the controls and PAR. Elevated levels of IL-1 beta, IL-17, IFN-gamma, TNF-alpha and MCP-1 were found in NARES compared to the controls as well as PAR. MIP-1 beta was elevated in NARES and PAR, while IL-4, IL-6 and G-CSF showed increased levels in NARES, and IL-5 was elevated in PAR only. Conclusions: In patients with NARES and PAR, eosinophils and mast cells appear to be the pivotal cells of inflammation, reflected by high levels of tryptase and ECP as well as IL-5 and GM-CSF as factors for eosinophil migration and survival. The elevated levels of proinflammatory cytokines in NARES may indicate the chronic, self-perpetuating process of inflammation in NARES which seems to be more pronounced than in PAR. IL-17 might be a factor for neutrophilic infiltration or be responsible for remodeling processes in NARES. Copyright (C) 2012 S. Karger AG, Base

Impact of Janus Kinase Inhibition with Tofacitinib on Fundamental Processes of Bone Healing

Both inflammatory diseases like rheumatoid arthritis (RA) and anti-inflammatory treatment of RA with glucocorticoids (GCs) or non-steroidal anti-inflammatory drugs (NSAIDs) negatively influence bone metabolism and fracture healing. Janus kinase (JAK) inhibition with tofacitinib has been demonstrated to act as a potent anti-inflammatory therapeutic agent in the treatment of RA, but its impact on the fundamental processes of bone regeneration is currently controversially discussed and at least in part elusive. Therefore, in this study, we aimed to examine the effects of tofacitinib on processes of bone healing focusing on recruitment of human mesenchymal stromal cells (hMSCs) into the inflammatory microenvironment of the fracture gap, chondrogenesis, osteogenesis and osteoclastogenesis. We performed our analyses under conditions of reduced oxygen availability in order to mimic the in vivo situation of the fracture gap most optimal. We demonstrate that tofacitinib dose-dependently promotes the recruitment of hMSCs under hypoxia but inhibits recruitment of hMSCs under normoxia. With regard to the chondrogenic differentiation of hMSCs, we demonstrate that tofacitinib does not inhibit survival at therapeutically relevant doses of 10-100 nM. Moreover, tofacitinib dose-dependently enhances osteogenic differentiation of hMSCs and reduces osteoclast differentiation and activity. We conclude from our data that tofacitinib may influence bone healing by promotion of hMSC recruitment into the hypoxic microenvironment of the fracture gap but does not interfere with the cartilaginous phase of the soft callus phase of fracture healing process. We assume that tofacitinib may promote bone formation and reduce bone resorption, which could in part explain the positive impact of tofacitinib on bone erosions in RA. Thus, we hypothesize that it will be unnecessary to stop this medication in case of fracture and suggest that positive effects on osteoporosis are likely

Wind erosion after steppe conversion in Kazakhstan

Semi-arid regions of Central Asia suffer from wind erosion due to expanding steppe conversion and unsustainable farming practices. Empirical data from field observations are needed to support the implementation of adapted management. In this study, a mobile wind tunnel was used for the first time in Kazakhstan to assess the soil's erodibility under real conditions. Field experiments were conducted on loamy sands with different initial conditions that are typical for the most erosive time of the year: a bare surface with a cloddy structure after recent steppe conversion, a weak crust on a plot with barley (Hordeum vulgare L.), and a plot with loose material in the rows of maize plants (Zea mays L.). Subsequently, different levels of mechanical stress (low, moderate, high) were considered to analyze the effect of disruptive forces soils experience during field cultivation (light cultivator, disc harrow, tractor tires) on possible soil losses. The results of wind tunnel experiments showed already great differences under initial conditions. The cloddy structure of the recent steppe conservation had the lowest susceptibility against wind erosion due to a good aggregation and a large roughness, resulting in soil loss of 12 g m−2. The plot grown with barley was less affected by wind erosion due to the weak crust, smaller distances between plants, and leaves close to the ground (soil loss of 34 g m−2). Maize was also the most problematic crop in the study area because wind can blow below the plant canopy without considerable resistance during the early growth stages. Additionally, existing deposits in the maize rows from previous erosion events led to the highest soil loss of 1609 g m−2. Mechanical stress by seedbed preparation generally increased the erodible fraction, resulting in higher soil losses (light cultivator: 198 ± 129 g m−2, disc harrow: 388 ± 258 g m−2). The most severe disruption of soil structure occurred on tractor tire tracks, causing a loss of 2767 ± 1810 g m−2. Consequently, the pulverizing effect of tractor tires on dry soil must be considered a serious emission source. Comparing the soil organic carbon content of topsoil and eroded material showed that organic carbon was enriched only in the aeolian sediments of the recently converted plot (+69%). We conclude that soils after steppe conversion need to be treated with particular care from the very beginning so that severe events from the past are not repeated

Cloud top heights and aerosol columnar properties from combined EarthCARE lidar and imager observations: the AM-CTH and AM-ACD products

The Earth Cloud, Aerosol and Radiation Explorer (EarthCARE) is a combination of multiple active and passive instruments on a single platform. The Atmospheric Lidar (ATLID) provides vertical information of clouds and aerosol particles along the satellite track. In addition, the Multi-Spectral Imager (MSI) collects multi-spectral information from the visible to the infrared wavelengths over a swath width of 150 km across the track. The ATLID–MSI Column Products processor (AM-COL) described in this paper combines the high vertical resolution of the lidar along track and the horizontal resolution of the imager across track to better characterize a three-dimensional scene. ATLID Level 2a (L2a) data from the ATLID Layer Products processor (A-LAY), MSI L2a data from the MSI Cloud Products processor (M-CLD) and the MSI Aerosol Optical Thickness processor (M-AOT), and MSI Level 1c (L1c) data are used as input to produce the synergistic columnar products: the ATLID–MSI Cloud Top Height (AM-CTH) and the ATLID–MSI Aerosol Column Descriptor (AM-ACD). The coupling of ATLID (measuring at 355 nm) and MSI (at ≥670 nm) provides multi-spectral observations of the aerosol properties. In particular, the Ångström exponent from the spectral aerosol optical thickness (AOT 355/670 nm) adds valuable information for aerosol typing. The AOT across track, the Ångström exponent and the dominant aerosol type are stored in the AM-ACD product. The accurate detection of the cloud top height (CTH) with lidar is limited to the ATLID track. The difference in the CTH detected by ATLID and retrieved by MSI is calculated along track. The similarity of MSI pixels across track with those along track is used to transfer the calculated CTH difference to the entire MSI swath. In this way, the accuracy of the CTH is increased to achieve the EarthCARE mission's goal of deriving the radiative flux at the top of the atmosphere with an accuracy of 10 W m−2 for a 100 km2 snapshot view of the atmosphere. The synergistic CTH difference is stored in the AM-CTH product. The quality status is provided with the products. It depends, e.g., on day/night conditions and the presence of multiple cloud layers. The algorithm was successfully tested using the common EarthCARE test scenes. Two definitions of the CTH from the model truth cloud extinction fields are compared: an extinction-based threshold of 20 Mm−1 provides the geometric CTH, and a cloud optical thickness threshold of 0.25 describes the radiative CTH. The first CTH definition was detected with ATLID and the second one with MSI. The geometric CTH is always higher than or equal to the radiative CTH

Novel High-Frequency Electric Field Sweeping Concept for High-Power Gyrotron Collectors

Future fusion power plants will require for plasma heating and noninductive current drive high-power gyrotrons, each of which generates 2 MW of continuous-wave microwave power, while another 2 MW in the spent electron beam is dissipated as heat on the collector wall. In today’s 1-MW continuous-wave gyrotrons, collector coils superimpose an ac (10–50 Hz) magnetic field to sweep the hot spots of spent electrons over a large area. However, to double today’s power, it will also be critical to reduce the hot spot dwell time preventing significant increase of material fatigue. This can be achieved by increasing the sweeping frequency. However, a higher frequency magnetic field would hardly penetrate the metallic collector vessel due to eddy currents. Instead of magnetic field, sweeping with electric fields is proposed for the first time. The presented mechanism is capable to apply several orders higher sweeping frequency to reduce the periodic variation of temperature, and thus, the device lifetime can be extended

Adult Hippocampal Neurogenesis and Plasticity in the Infrapyramidal Bundle of the Mossy Fiber Projection: I. Co-Regulation by Activity

Besides the massive plasticity at the level of synapses, we find in the hippocampus of adult mice and rats two systems with very strong macroscopic structural plasticity: adult neurogenesis, that is the lifelong generation of new granule cells, and dynamic changes in the mossy fibers linking the dentate gyrus to area CA3. In particular the anatomy of the infrapyramidal mossy fiber tract (IMF) changes in response to a variety of extrinsic and intrinsic stimuli. Because mossy fibers are the axons of granule cells, the question arises whether these two types of plasticity are linked. Using immunohistochemistry for markers associated with axonal growth and pro-opiomelanocortin (POMC)–GFP mice to visualize the post-mitotic maturation phase of adult hippocampal neurogenesis, we found that newly generated mossy fibers preferentially but not exclusively contribute to the IMF. The neurogenic stimulus of an enriched environment increased the volume of the IMF. In addition, the IMF grew with a time course consistent with axonal outgrowth from the newborn neurons after the induction of neurogenic seizures using kainate. These results indicate that two aspects of plasticity in the adult hippocampus, mossy fiber size and neurogenesis, are related and may share underlying mechanisms. In a second part of this study, published separately (Krebs et al., 2011) we have addressed the question of whether there is a shared genetics underlying both traits

Toward the First Continuous Wave Compatible Multistage Depressed Collector Design for High Power Gyrotrons

The multistage depressed collector (MDC) is essential to significantly increase the overall efficiency of the gyrotron. To date, a short pulse (SP) MDC prototype system has been manufactured and is currently under test. The long-term goal that makes the most sense is to use MDCs on 2-MW fusion gyrotrons in continuous wave (CW) operation. To achieve this, a CW MDC system based on the same physical principle as the SP system is designed and analyzed for the first time. The highlights of this design are the sweeping systems to keep the thermal loading within an acceptable limit when the MDC is operated in CW. In the present analysis, the expected performance and size of the new CW MDC design are compared with that of the SP MDC prototype and with the corresponding single-stage depressed collectors (SDCs) as a reference. In addition, the effects of thermal expansion in CW operation are analyzed and discussed

A Randomized Controlled Comparison of Image Quality

Background The purpose of the present study was to compare the image quality of spinal magnetic resonance (MR) imaging performed on a high-field horizontal open versus a short-bore MR scanner in a randomized controlled study setup. Methods Altogether, 93 (80% women, mean age 53) consecutive patients underwent spine imaging after random assignement to a 1-T horizontal open MR scanner with a vertical magnetic field or a 1.5-T short-bore MR scanner. This patient subset was part of a larger cohort. Image quality was assessed by determining qualitative parameters, signal-to-noise (SNR) and contrast-to-noise ratios (CNR), and quantitative contour sharpness. Results The image quality parameters were higher for short-bore MR imaging. Regarding all sequences, the relative differences were 39% for the mean overall qualitative image quality, 53% for the mean SNR values, and 34–37% for the quantitative contour sharpness (P<0.0001). The CNR values were also higher for images obtained with the short-bore MR scanner. No sequence was of very poor (nondiagnostic) image quality. Scanning times were significantly longer for examinations performed on the open MR scanner (mean: 32±22 min versus 20±9 min; P<0.0001). Conclusions In this randomized controlled comparison of spinal MR imaging with an open versus a short-bore scanner, short-bore MR imaging revealed considerably higher image quality with shorter scanning times

Variability of doublecortin-associated dendrite maturation in adult hippocampal neurogenesis is independent of the regulation of precursor cell proliferation

BACKGROUND: In the course of adult hippocampal neurogenesis most regulation takes place during the phase of doublecortin (DCX) expression, either as pro-proliferative effect on precursor cells or as survival-promoting effect on postmitotic cells. We here obtained quantitative data about the proliferative population and the dynamics of postmitotic dendrite development during the period of DCX expression. The question was, whether any indication could be obtained that the initiation of dendrite development is timely bound to the exit from the cell cycle. Alternatively, the temporal course of morphological maturation might be subject to additional regulatory events. RESULTS: We found that (1) 20% of the DCX population were precursor cells in cell cycle, whereas more than 70% were postmitotic, (2) the time span until newborn cells had reached the most mature stage associated with DCX expression varied between 3 days and several weeks, (3) positive or negative regulation of precursor cell proliferation did not alter the pattern and dynamics of dendrite development. Dendrite maturation was largely independent of close contacts to astrocytes. CONCLUSION: These data imply that dendrite maturation of immature neurons is initiated at varying times after cell cycle exit, is variable in duration, and is controlled independently of the regulation of precursor cell proliferation. We conclude that in addition to the major regulatory events in cell proliferation and selective survival, additional micro-regulatory events influence the course of adult hippocampal neurogenesis