MRI/Photoluminescence Dual-Modal Imaging Magnetic PLGA Nanocapsules for Theranostics

Developing multifunctional and biocompatible drug delivery nanoplatforms that integrate high drug loads and multiple imaging modalities avoiding cross-interferences is extremely challenging. Here we report on the successful chemical reaction of the high quantum yield biodegradable and photoluminescent polyester (BPLP) with the poly(lactic-co-glycolic acid) (PLGA) polymer to fabricate biocompatible photoluminescent nanocapsules (NCs). Furthermore, we transform the PLGA-BPLP NCs into a magnetic resonance (MR)/photoluminescence dual-modal imaging theranostic platform by incorporating superparamagnetic iron oxide nanoparticles (SPIONs) into the polymeric shell. In vitro phantoms confirmed the excellent MRI-r2 relaxivity values of the NCs whilst the cellular uptake of these NCs was clearly observed by fluorescence optical imaging. Besides, the NCs (mean size ~270 nm) were loaded with ~1 wt% of a model protein (BSA) and their PEGylation provided a more hydrophilic surface. The NCs show biocompatibility in vitro, as hCMEC/D3 endothelial cells viability was not affected for particle concentration up to 500 μg/mL. Interestingly, NCs decorated with SPIONs can be exploited for magnetic guiding and retention.This work was partially supported by the Spanish Ministry of Science, Innovation and Universities through the grants PCIN-2017-090, RTI2018-096273-B-I00, CTQ2017-87637-R, SAF2017-87670-R, SEV-2015-0496 and MDM-2017-0720 and by the Generalitat de Catalunya grants (2017SGR765 & 2017SGR1427). Yajie Zhang was supported by the China Scholarship Council (CSC). The Acciones Complementarias program from the Instituto de Salud Carlos III, Spain, co-financed by the European Regional Development Fund (AC17/00004 grant) as part of the MAGBBRIS project (Euronanomed III 8th joint call), and the RETICS INVICTUS RD16/0019/0021 were acknowledged. Miguel Servet program (CPII15/00003) from Fondo de Investigaciones Sanitarias-Instituto de Salud Carlos III and ERDF, supported A. Roig research contract.Peer reviewe

Epitaxial stabilization of ε-Fe2O3 (00l) thin films on SrTiO3 (111)

This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics.Thin films of the metastable and elusive ε-Fe2O3 have been epitaxially stabilized on SrTiO3 (111) substrates. The ε-Fe2O3 films present a (001) orientation perpendicular to the substrate and three in-plane domains measuring a few nanometers and showing atomically sharp interfaces. We argue that this domain structure, rather than the epitaxial-strain, plays an essential role in stabilizing the ε-Fe2O3 by minimizing the energy of (100) surfaces. The ε-Fe2O3 films show a large in-plane coercivity ∼ 8 kOe which combined with the magnetoelectric character claimed for this oxide may lead to novel applications in spintronics

Geographical, Socioeconomic, and Gender Inequalities in Opioid Use in Catalonia

Background: In recent years, worldwide opioid use has seen a sharp increase, especially for the treatment of chronic non-cancer pain. Catalonia is no exception to this trend. However, no recent studies have addressed the socioeconomic and gender inequalities in opioid use in the different geographical areas of Catalonia. Methods: We performed an ecological study to analyse the associations between socioeconomic status, gender and the use of opioids in the 372 Health Areas of Catalonia. Robust Poisson models were performed to analyse the data provided from the Central Register of Insured Persons and dispensing data from the Electronic Prescription Database. Results: The results show that socioeconomic status has a major impact on opioid use, with the most deprived areas presenting the highest levels of use. There are major inequalities in the DDD/1,000 inhabitants per areas. Moreover, women have much higher utilization rates than men, especially in more deprived areas. The greatest difference is observed in the use of weak opioids in women: the DDD/1,000 inhabitants per day was 2.34 in the area with the lowest use, compared with 22.18 in the area with the highest use. Conclusions: Our findings suggest that stronger action is needed to promote best practices in prescribing for chronic pain and to reduce socioeconomic and gender variation between geographical areas. This study provides a model for routine monitoring of opioid prescription for targeted interventions aimed at lowering high-dose consumption in specifically identified areas

Magnetic Mesoporous Silica Nanorods Loaded with Ceria and Functionalized with Fluorophores for Multimodal Imaging

Multifunctional magnetic nanocomposites based on mesoporous silica have a wide range of potential applications in catalysis, biomedicine, or sensing. Such particles combine responsiveness to external magnetic fields with other functionalities endowed by the agents loaded inside the pores or conjugated to the particle surface. Different applications might benefit from specific particle morphologies. In the case of biomedical applications, mesoporous silica nanospheres have been extensively studied while nanorods, with a more challenging preparation, have attracted much less attention despite the positive impact on the therapeutic performance shown by seminal studies. Here, we report on a sol-gel synthesis of mesoporous rodlike silica particles of two distinct lengths (1.4 and 0.9 μm) and aspect ratios (4.7 and 2.2) using Pluronic P123 as a structure-directing template and rendering ∼1 g of rods per batch. Iron oxide nanoparticles have been synthesized within the pores yielding maghemite (γ-FeO) nanocrystals of elongated shape (∼7 nm × 5 nm) with a [110] preferential orientation along the rod axis and a superparamagnetic character. The performance of the rods as T-weighted MRI contrast agents has also been confirmed. In a subsequent step, the mesoporous silica rods were loaded with a cerium compound and their surface was functionalized with fluorophores (fluorescamine and Cyanine5) emitting at λ = 525 and 730 nm, respectively, thus highlighting the possibility of multiple imaging modalities. The biocompatibility of the rods was evaluated in vitro in a zebrafish (Danio rerio) liver cell line (ZFL), with results showing that neither long nor short rods with magnetic particles caused cytotoxicity in ZFL cells for concentrations up to 50 μg/ml. We advocate that such nanocomposites can find applications in medical imaging and therapy, where the influence of shape on performance can be also assesse

Estudi qualitatiu per conèixer què és una bona mort: experiències i vivències de pacients, familiars i professionals en el sistema de salut català

Mort; Estudi qualitatiu; PacientsMuerte; Estudio cualitativo; PacientesDeath; Qualitative study; PatientsL’objectiu de l'estudi és conèixer l’opinió sobre què es considera una bona mort, els seus elements clau, les barreres i els facilitadors, a més de les necessitats no cobertes en el sistema de salut per facilitar-la. S’han fet vint-i-tres entrevistes etnogràfiques amb pacients i familiars, així com tres grups de discussió amb trenta-un professionals i representants d’associacions de pacients i familiars vinculats a l’atenció al final de la vida

Què pot facilitar o dificultar una bona mort?

Mort; Estudi qualitatiu; Bona mortMuerte; Estudio cualitativo; Buena muerteDeath; Case report; Good deathL’objectiu de l'estudi és conèixer l’opinió sobre què es considera una bona mort, els seus elements clau, les barreres i els facilitadors, a més de les necessitats no cobertes en el sistema de salut per facilitar-la. Per promoure una major visibilitat d’aquestes necessitats envers el final de vida i la pròpia mort, s’ha portat a terme un estudi qualitatiu amb pacients, familiars i professionals en el marc de l’Observatori de la Mort

Infusion of Phagocytic Macrophages Overexpressing CPT1a Ameliorates Kidney Fibrosis in the UUO Model

Phagocytosis is an inherent function of tissue macrophages for the removal of apoptotic cells and cellular debris during acute and chronic injury; however, the dynamics of this event during fibrosis development is unknown. We aim to prove that during the development of kidney fibrosis in the unilateral ureteral obstruction (UUO) model, there are some populations of macrophage with a reduced ability to phagocytose, and whether the infusion of a population of phagocytic macrophages could reduce fibrosis in the murine model UUO. For this purpose, we have identified the macrophage populations during the development of fibrosis and have characterized their phagocytic ability and their expression of CPT1a. Furthermore, we have evaluated the therapeutic effect of macrophages overexpressing CPT1a with high phagocytic skills. We evidenced that the macrophage population which exhibits high phagocytic ability (F4/80low-CD11b) in fibrotic animals decreases during the progression of fibrosis while the macrophage population with lower phagocytic ability (F4/80high-CD11b) in fibrotic conditions, conversely, increases and CPT1a macrophage cell therapy with a strengthening phagocytic ability is associated with a therapeutic effect on kidney fibrosis. We have developed a therapeutic approach to reduce fibrosis in the UUO model by enrichment of the kidney resident macrophage population with a higher proportion of exogenous phagocytic macrophages overexpressing CPT1a

Novel role of FATP1 in mitochondrial fatty acid oxidation in skeletal muscle cells

Carnitine palmitoyltransferase 1 (CPT1) catalyzes the first step in long-chain fatty acid import into mitochondria, and it is believed to be rate limiting for beta-oxidation of fatty acids. However, in muscle, other proteins may collaborate with CPT1. Fatty acid translocase/CD36 (FAT/CD36) may interact with CPT1 and contribute to fatty acid import into mitochondria in muscle. Here, we demonstrate that another membrane-bound fatty acid binding protein, fatty acid transport protein 1 (FATP1), collaborates with CPT1 for fatty acid import into mitochondria. Overexpression of FATP1 using adenovirus in L6E9 myotubes increased both fatty acid oxidation and palmitate esterification into triacylglycerides. Moreover, immunocytochemistry assays in transfected L6E9 myotubes showed that FATP1 was present in mitochondria and coimmunoprecipitated with CPT1 in L6E9 myotubes and rat skeletal muscle in vivo. The cooverexpression of FATP1 and CPT1 also enhanced mitochondrial fatty acid oxidation, similar to the cooverexpression of FAT/CD36 and CPT1. However, etomoxir, an irreversible inhibitor of CPT1, blocked all these effects. These data reveal that FATP1, like FAT/CD36, is associated with mitochondria and has a role in mitochondrial oxidation of fatty acids

Anàlisi territorial de la mortalitat a Catalunya: 1999-2004

Mortalitat; Catalunya; Mortality; Catalonia; Mortalidad; CataluñaAquesta publicació té com a objectiu principal posar a l’abast dels professionals de la salut dades bàsiques de mortalitat de les comarques com una forma d’aproximació al coneixement de l’estat de salut d’aquests territoris. Per aquest motiu s’inclou un nombre important de resultats, alguns dels quals poden semblar redundants, però que des del punt de vista del seu ús poden tenir diferents indicacions o avantatges

Blocking Placental Class G Immunoglobulin Transfer Prevents NMDA Receptor Antibody Effects in Newborn Mice

To determine in a mouse model whether neonatal Fc receptor (FcRn) blockade prevents the placental transfer of class G immunoglobulin (IgG) derived from patients with anti-NMDA receptor (NMDAR) encephalitis and their pathogenic effects on the fetuses and offspring.Pregnant C57BL/6J mice were administered via tail vein FcRn antibody (FcRn-ab) or saline solution 6 hours before administration of patients' or controls' IgG on days 14, 15, and 16 of gestation. Three experimental groups were established: mice receiving controls' IgG, patients' IgG, or patients' IgG along with pretreatment with FcRn-ab. Immunohistochemical staining, confocal microscopy, hippocampal long-term potentiation, and standardized developmental and behavioral tasks were used to assess the efficacy of treatment with FcRn-ab.In pregnant mice that received patients' IgG, treatment with FcRn-ab prevented the IgG from reaching the fetal brain, abrogating the decrease of NMDAR clusters and the reduction of cortical plate thickness that were observed in fetuses from untreated pregnant mice. Moreover, among the offspring of mothers that received patients' IgG, those whose mothers were treated with FcRn-ab did not develop the alterations that occurred in offspring of untreated mothers, including impairment in hippocampal plasticity, delay in innate reflexes, and visuospatial memory deficits.FcRn blockade prevents placental transfer of IgG from patients with anti-NMDAR encephalitis and abrogates the synaptic and neurodevelopmental alterations caused by patients' antibodies. This model has potential therapeutic implications for other antibody-mediated diseases of the CNS during pregnancy