Magnetic nanoparticles (MNPs) have been widely used to increase the efficacy of chemotherapeutics, largely through passive accumulation provided by the enhanced permeability and retention effect. ...Their incorporation into biopolymer coatings enables the preparation of magnetic field-responsive, biocompatible nanoparticles that are well dispersed in aqueous media. Here we describe a synthetic route to prepare functionalized, stable magnetite nanoparticles (MNPs) coated with a temperature-responsive polymer, by means of the hydrothermal method combined with an oil/water (o/w) emulsion process. The effects of both pH and temperature on the electrophoretic mobility and surface charge of these MNPs are investigated. The magnetite/polymer composition of these systems is detected by Fourier Transform Infrared Spectroscopy (FTIR) and quantified by thermogravimetric analysis. The therapeutic possibilities of the designed nanostructures as effective heating agents for magnetic hyperthermia are demonstrated, and specific absorption rates as high as 150 W/g, with 20 mT magnetic field and 205 kHz frequency, are obtained. This magnetic heating response could provide a promising nanoparticle system for combined diagnostics and cancer therapy.
The past decades have provided valuable information on how animals age in the wild. However, examples of male reproductive senescence are scarce. In particular, few studies have described an ...age-related decline in the expression of conspicuous traits influencing mating success. Red ornaments could be good candidates to detect this decline because their expression may depend on the availability of pigments (carotenoids) related to oxidative stress, the latter frequently linked to senescence. Furthermore, it has been argued that efficient mitochondrial metabolism is key to express red carotenoid-based ornaments, and mitochondrial dysfunction is usually associated with senescence. We studied the age-linked expression of a red carotenoid-based trait: the yellowto-red plumage coloration of male common crossbills (Loxia curvirostra). This coloration has recently been experimentally related to mitochondrial function. Here, we analyzed longitudinal plumage coloration data obtained throughout 28 years in free-living birds. We detected an initial increase in redness during the first 2 years of life and a subsequent decline. The relationship between color and age was unrelated to within-individual body mass variability. As far as we know, this is the first demonstration of an age-related ketocarotenoid-based color decrease detected by simultaneously testing within- and between-individual variability in wild animals.
Background
Despite the socioeconomic importance of allergic rhinitis (AR), very few prospective studies have been performed under conditions of clinical practice and with a sufficiently long ...observation period outside the clinical trial scenario. We prospectively estimated the direct and indirect costs of AR in patients attending specialized clinics in Spain.
Methods
Patients were recruited at random from allergy outpatient clinics in 101 health centers throughout Spain over 12 months. We performed a multicenter, observational, prospective study under conditions of clinical practice. We analyzed direct costs from a funder perspective (healthcare costs) and from a societal perspective (healthcare and non–healthcare costs). Indirect costs (absenteeism and presenteeism productivity lost in the workplace) were also calculated. The cost of treating conjunctivitis was evaluated alongside that of AR.
Results
The total mean cost of AR per patient‐year (n = 498) was €2326.70 (direct, €553.80; indirect, €1772.90). Direct costs were significantly higher in women (€600.34 vs €484.46, P = 0.02). Total costs for intermittent AR were significantly lower than for persistent AR (€1484.98 vs €2655.86, P < 0.001). Total indirect costs reached €1772.90 (presenteeism, €1682.71; absenteeism, €90.19). The direct costs of AR in patients with intermittent asthma (€507.35) were lower than in patients with mild‐persistent asthma (€719.07) and moderate‐persistent asthma (€798.71) (P = 0.006).
Conclusions
The total cost of AR for society is considerable. Greater frequency of symptoms and more severe AR are associated with higher costs. Indirect costs are almost threefold direct costs, especially in presenteeism. A reduction in presenteeism would generate considerable savings for society.
Biomedical magnetic colloids commonly used in magnetic hyperthermia experiments often display a bidisperse structure, i.e., are composed of stable nanoclusters coexisting with well-dispersed ...nanoparticles. However, the influence of nanoclusters in the optimization of colloids for heat dissipation is usually excluded. In this work, bidisperse colloids are used to analyze the effect of nanoclustering and long-range magnetic dipolar interaction on the magnetic hyperthermia efficiency. Two kinds of colloids, composed of magnetite cores with mean sizes of around 10 and 18 nm, coated with oleic acid and dispersed in hexane, and coated with meso-2,3-dimercaptosuccinic acid and dispersed in water, were analyzed. Small-angle X-ray scattering was applied to thoroughly characterize nanoparticle structuring. We proved that the magnetic hyperthermia performances of nanoclusters and single nanoparticles are distinctive. Nanoclustering acts to reduce the specific heating efficiency whereas a peak against concentration appears for the well-dispersed component. Our experiments show that the heating efficiency of a magnetic colloid can increase or decrease when dipolar interactions increase and that the colloid concentration, i.e., dipolar interaction, can be used to improve magnetic hyperthermia. We have proven that the power dissipated by an ensemble of dispersed magnetic nanoparticles becomes a nonextensive property as a direct consequence of the long-range nature of dipolar interactions. This knowledge is a key point in selecting the correct dose that has to be injected to achieve the desired outcome in intracellular magnetic hyperthermia therapy.
In spite of the extensive potential of human mesenchymal stem cells (hMSCs) in cell therapy, little is known about the molecular mechanisms that regulate their therapeutic properties. We aimed to ...identify microRNAs (miRNAs) involved in controlling the transition between the resting and reparative phenotypes of hMSCs, hypothesizing that these miRNAs must be present in the undifferentiated cells and downregulated to allow initiation of distinct activation/differentiation programs. Differential miRNA expression analyses revealed that miR-335 is significantly downregulated upon hMSC differentiation. In addition, hMSCs derived from a variety of tissues express miR-335 at a higher level than human skin fibroblasts, and overexpression of miR-335 in hMSCs inhibited their proliferation and migration, as well as their osteogenic and adipogenic potential. Expression of miR-335 in hMSCs was upregulated by the canonical Wnt signaling pathway, a positive regulator of MSC self-renewal, and downregulated by interferon-γ (IFN-γ), a pro-inflammatory cytokine that has an important role in activating the immunomodulatory properties of hMSCs. Differential gene expression analyses, in combination with computational searches, defined a cluster of 62 putative target genes for miR-335 in hMSCs. Western blot and 3'UTR reporter assays confirmed RUNX2 as a direct target of miR-335 in hMSCs. These results strongly suggest that miR-335 downregulation is critical for the acquisition of reparative MSC phenotypes.
Arsenic and mercury are potentially toxic elements of concern for soil, surficial and ground waters, and sediments. In this work various geochemical and hydrogeological tools were used to study a ...paradigmatic case of the combined effects of the abandonment of Hg- and As-rich waste on these environmental compartments. Continuous weathering of over 40years has promoted As and Hg soil pollution (thousands of ppm) in the surroundings of a former Hg mining-metallurgy site and affected the water quality of a nearby river and shallow groundwater. In particular, the high availability of As both in soils and waste was identified as one of the main determinants of contaminant distribution, whereas the impact of Hg was found to be minor, which is explained by lower mobility. Furthermore, potential additional sources of pollution (coal mining, high natural backgrounds, etc.) discharging into the study river were revealed less significant than the contaminants generated in the Hg-mining area. The transport and deposition of pollutants within the water cycle has also affected several kilometres downstream of the release areas and the chemistry of stream sediments. Overall, the environmental compartments studies held considerable concentrations of Hg and As, as remarkably revealed by the average contaminant load released in the river (several tons of As per year) and the accumulation of toxic elements in sediments (enrichment factors of As and Hg above 35).
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•40-years abandoned As- and Hg-rich waste promoted soil pollution.•As showed greater mobility and dispersion than Hg.•Waste stock-piled and highly polluted soil affected water and groundwater quality.•River sediments were severely enriched in As and Hg.
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The osteogenic and angiogenic responses to metal macroporous scaffolds coated with silicon substituted hydroxyapatite (SiHA) and decorated with vascular endothelial growth factor ...(VEGF) have been evaluated in vitro and in vivo. Ti6Al4V-ELI scaffolds were prepared by electron beam melting and subsequently coated with Ca10(PO4)5.6(SiO4)0.4(OH)1.6 following a dip coating method. In vitro studies demonstrated that SiHA stimulates the proliferation of MC3T3-E1 pre-osteoblastic cells, whereas the adsorption of VEGF stimulates the proliferation of EC2 mature endothelial cells. In vivo studies were carried out in an osteoporotic sheep model, evidencing that only the simultaneous presence of both components led to a significant increase of new tissue formation in osteoporotic bone.
Reconstruction of bones after severe trauma or tumors extirpation is one of the most challenging tasks in the field of orthopedic surgery. This scenario is even more complicated in the case of osteoporotic patients, since their bone regeneration capability is decreased. In this work we present a porous implant that promotes bone regeneration even in osteoporotic bone. By coating the implant with osteogenic bioceramics such as silicon substituted hydroxyapatite and subsequent adsorption of vascular endothelial growth factor, these implants stimulate the bone ingrowth when they are implanted in osteoporotic sheep.
► Well dispersed nanocrystals in polyurethane due to hydrogen bonding interactions. ► Low nanocrystals content in polyurethane nanocomposites leads to tough material. ► An increase in nanocrystals ...content induced soft and hard segment crystallization. ► Cellulose network formation can be affected with polyurethane microstructure.
Cellulose nanocrystals (CNC) successfully obtained from microcrystalline cellulose (MCC) were dispersed in a thermoplastic polyurethane as matrix. Nanocomposites containing 1.5, 5, 10 and 30wt% CNC were prepared by solvent casting procedure and properties of the resulting films were evaluated from the viewpoint of polyurethane microphase separated structure, soft and hard domains. CNC were effectively dispersed in the segmented thermoplastic elastomeric polyurethane (STPUE) matrix due to the favorable matrix–nanocrystals interactions through hydrogen bonding. Cellulose nanocrystals interacted with both soft and hard segments, enhancing stiffness and stability versus temperature of the nanocomposites. Thermal and mechanical properties of STPUE/CNC nanocomposites have been associated to the generated morphologies investigated by AFM images.
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