Behaviour of adipose-derived canine mesenchymal stem cells after superparamagnetic iron oxide nanoparticles labelling for magnetic resonance imaging

Background: Therapy with mesenchymal stem cells (MSCs) has been reported to provide beneficial effects in the treatment of neurological and orthopaedic disorders in dogs. The exact mechanism of action is poorly understood. Magnetic resonance imaging (MRI) gives the opportunity to observe MSCs after clinical administration. To visualise MSCs with the help of MRI, labelling with an MRI contrast agent is necessary. However, it must be clarified whether there is any negative influence on cell function and viability after labelling prior to clinical administration. Results: For the purpose of the study, seven samples with canine adipose-derived stem cells were incubated with superparamagnetic iron oxide nanoparticles (SPIO: 319.2 µg/mL Fe) for 24 h. The internalisation of the iron particles occurred via endocytosis. SPIO particles were localized as free clusters in the cytoplasm or within lysosomes depending on the time of investigation. The efficiency of the labelling was investigated using Prussian blue staining and MACS assay. After 3 weeks the percentage of SPIO labelled canine stem cells decreased. Phalloidin staining showed no negative effect on the cytoskeleton. Labelled cells underwent osteogenic and adipogenic differentiation. Chondrogenic differentiation occurred to a lesser extent compared with a control sample. MTT-Test and wound healing assay showed no influence of labelling on the proliferation. The duration of SPIO labelling was assessed using a 1 Tesla clinical MRI scanner and T2 weighted turbo spin echo and T2 weighted gradient echo MRI sequences 1, 2 and 3 weeks after labelling. The hypointensity caused by SPIO lasted for 3 weeks in both sequences. Conclusions: An Endorem labelling concentration of 319.2 µg/mL Fe (448 µg/mL SPIO) had no adverse effects on the viability of canine ASCs. Therefore, this contrast agent could be used as a model for iron oxide labelling agents. However, the tracking ability in vivo has to be evaluated in further studies

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

Wind energy production in forests conflicts with tree-roosting bats

Many countries are investing heavily in wind power generation,1 triggering a high demand for suitable land. As a result, wind energy facilities are increasingly being installed in forests,2,3 despite the fact that forests are crucial for the protection of terrestrial biodiversity.4 This green-green dilemma is particularly evident for bats, as most species at risk of colliding with wind turbines roost in trees.2 With some of these species reported to be declining,5,6,7,8 we see an urgent need to understand how bats respond to wind turbines in forested areas, especially in Europe where all bat species are legally protected. We used miniaturized global positioning system (GPS) units to study how European common noctule bats (Nyctalus noctula), a species that is highly vulnerable at turbines,9 respond to wind turbines in forests. Data from 60 tagged common noctules yielded a total of 8,129 positions, of which 2.3% were recorded at distances <100 m from the nearest turbine. Bats were particularly active at turbines <500 m near roosts, which may require such turbines to be shut down more frequently at times of high bat activity to reduce collision risk. Beyond roosts, bats avoided turbines over several kilometers, supporting earlier findings on habitat loss for forest-associated bats.10 This habitat loss should be compensated by developing parts of the forest as refugia for bats. Our study highlights that it can be particularly challenging to generate wind energy in forested areas in an ecologically sustainable manner with minimal impact on forests and the wildlife that inhabit them

Precision timing of PSR J1012+5307 and strong-field GR tests

We report on the high precision timing analysis of the pulsar-white dwarf binary PSR J1012+5307. Using 15 years of multi-telescope data from the European Pulsar Timing Array (EPTA) network, a significant measurement of the variation of the orbital period is obtained. Using this ideal strong-field gravity laboratory we derive theory independent limits for both the dipole radiation and the variation of the gravitational constant.Comment: 3 pages, Proceedings of the 12th Marcel Grossmann Meeting on General Relativity (MG 12

Dementia assessment and management in primary care settings: a survey of current provider practices in the United States.

BACKGROUND:Primary care providers (PCPs) are typically the first to screen and evaluate patients for neurocognitive disorders (NCDs), including mild cognitive impairment and dementia. However, data on PCP attitudes and evaluation and management practices are sparse. Our objective was to quantify perspectives and behaviors of PCPs and neurologists with respect to NCD evaluation and management. METHODS:A cross-sectional survey with 150 PCPs and 50 neurologists in the United States who evaluated more than 10 patients over age 55 per month. The 51-item survey assessed clinical practice characteristics, and confidence, perceived barriers, and typical practices when diagnosing and managing patients with NCDs. RESULTS:PCPs and neurologists reported similar confidence and approaches to general medical care and laboratory testing. Though over half of PCPs performed cognitive screening or referred patients for cognitive testing in over 50% of their patients, only 20% reported high confidence in interpreting results of cognitive tests. PCPs were more likely to order CT scans than MRIs, and only 14% of PCPs reported high confidence interpreting brain imaging findings, compared to 70% of specialists. Only 21% of PCPs were highly confident that they correctly recognized when a patient had an NCD, and only 13% were highly confident in making a specific NCD diagnosis (compared to 72 and 44% for neurologists, both p &lt; 0.001). A quarter of all providers identified lack of familiarity with diagnostic criteria for NCD syndromes as a barrier to clinical practice. CONCLUSIONS:This study demonstrates how PCPs approach diagnosis and management of patients with NCDs, and identified areas for improvement in regards to&nbsp;cognitive testing and neuroimaging. This study also identified all&nbsp;providers' lack of familiarity with published diagnostic criteria for NCD syndromes. These findings may inform the development of new policies and interventions to help providers improve the efficacy of their decision processes and deliver better quality care to patients with NCDs

The Mass Function of Super Giant Molecular Complexes and Implications for Forming Young Massive Star Clusters in the Antennae (NGC 4038/39)

We have used previously published observations of the CO emission from the Antennae (NGC 4038/39) to study the detailed properties of the super giant molecular complexes with the goal of understanding the formation of young massive star clusters. Over a mass range from 5E6 to 9E8 solar masses, the molecular complexes follow a power-law mass function with a slope of -1.4 +/- 0.1, which is very similar to the slope seen at lower masses in molecular clouds and cloud cores in the Galaxy. Compared to the spiral galaxy M51, which has a similar surface density and total mass of molecular gas, the Antennae contain clouds that are an order of magnitude more massive. Many of the youngest star clusters lie in the gas-rich overlap region, where extinctions as high as Av~100 imply that the clusters must lie in front of the gas. Combining data on the young clusters, thermal and nonthermal radio sources, and the molecular gas suggests that young massive clusters could have formed at a constant rate in the Antennae over the last 160 Myr and that sufficient gas exists to sustain this cluster formation rate well into the future. However, this conclusion requires that a very high fraction of the massive clusters that form initially in the Antennae do not survive as long as 100 Myr. Finally, we compare our data with two models for massive star cluster formation and conclude that the model where young massive star clusters form from dense cores within the observed super giant molecular complexes is most consistent with our current understanding of this merging system. (abbreviated)Comment: 40 pages, four figures; accepted for publication in Ap

Interleukin-6, age, and corpus callosum integrity.

The contribution of inflammation to deleterious aging outcomes is increasingly recognized; however, little is known about the complex relationship between interleukin-6 (IL-6) and brain structure, or how this association might change with increasing age. We examined the association between IL-6, white matter integrity, and cognition in 151 community dwelling older adults, and tested whether age moderated these associations. Blood levels of IL-6 and vascular risk (e.g., homocysteine), as well as health history information, were collected. Processing speed assessments were administered to assess cognitive functioning, and we employed tract-based spatial statistics to examine whole brain white matter and regions of interest. Given the association between inflammation, vascular risk, and corpus callosum (CC) integrity, fractional anisotropy (FA) of the genu, body, and splenium represented our primary dependent variables. Whole brain analysis revealed an inverse association between IL-6 and CC fractional anisotropy. Subsequent ROI linear regression and ridge regression analyses indicated that the magnitude of this effect increased with age; thus, older individuals with higher IL-6 levels displayed lower white matter integrity. Finally, higher IL-6 levels were related to worse processing speed; this association was moderated by age, and was not fully accounted for by CC volume. This study highlights that at older ages, the association between higher IL-6 levels and lower white matter integrity is more pronounced; furthermore, it underscores the important, albeit burgeoning role of inflammatory processes in cognitive aging trajectories

Cytokine patterns in nasal secretion of non-atopic patients distinguish between chronic rhinosinusitis with or without nasal polys

Background: Being one of the most common nasal diseases, chronic rhinosinusitis (CRS) is subdivided into CRS with nasal polyps (NP) and CRS without nasal polyps (CRSsNP). CRSsNP presents itself with a T(H)1 milieu and neutrophil infiltration, while NP is characterised by a mixed T(H)1/T(H)2 profile and an influx of predominantly eosinophils, plasma cells and mast cells. For the purpose of discovering disease-specific cytokine profiles, the present study compares levels of mediators and cytokines in nasal secretions between CRSsNP, NP, and healthy controls. Methods: The study included 45 participants suffering from NP, 48 suffering from CRSsNP and 48 healthy controls. Allergic rhinitis constituted an exclusion criterion. Nasal secretions, sampled using the cotton wool method, were analysed for IL-4, IL-5, IL-10, IL-12, IL-13, IL-17, IL-8, GM-CSF, G-CSF, IFN-gamma, MCP-1, MIP-1 alpha, MIP-1 beta, eotaxin, and RANTES, and for ECP and tryptase, using Bio-Plex Cytokine assay or ELISA, respectively. Results: Elevated levels of IL-5, IL-17, G-CSF, MCP-1, MIP-1 alpha, MIP-1 beta, ECP, and tryptase, as well as decreased levels of IL-10, IL-12, IL-13, and IFN-gamma were detected in NP. CRSsNP presented increased levels of RANTES and MIP-1 beta while IL-13 was decreased. No differences between the three groups were found for IL-4, IL-8, GM-CSF, and eotaxin. Conclusions: The present work suggests a disequilibrium of T(H)1 and T(H)2, together with a down-regulation of regulatory T lymphocytes and up-regulated T(H)17 in NP. Moreover, elevated levels of diverse mediators represent the activation of various inflammatory cells in this disease entity. The inflammation in CRSsNP, however, is only weakly depicted in nasal secretions. Therefore, cytokines in nasal secretions may provide helpful information for differential diagnosis