882 research outputs found

    Morphology-properties relationship on nanocomposite films based on poly(styrene-block-diene-block-styrene) copolymers and silver nanoparticles

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    A comparative study on the self-assembled nanostructured morphology and the rheological and mechanical prop- erties of four different triblock copolymers, based on poly(styrene-block-butadiene-block-styrene) and poly(styrene-block- isoprene-block-styrene) matrices, and of their respective nanocomposites with 1 wt% silver nanoparticles, is reported in this work. In order to obtain well-dispersed nanoparticles in the block copolymer matrix, dodecanethiol was used as surfac- tant, showing good affinity with both nanoparticles and the polystyrene phase of the matrices as predicted by the solubility parameters calculated based on Hoftyzer and Van Krevelen theory. The block copolymer with the highest PS content shows the highest tensile modulus and tensile strength, but also the smallest elongation at break. When silver nanoparticles treated with surfactant were added to the block copolymer matrices, each system studied shows higher mechanical properties due to the good dispersion and the good interface of Ag nanoparticles in the matrices. Furthermore, it has been shown that semi- empirical models such as Guth and Gold equation and Halpin-Tsai model can be used to predict the tensile modulus of the analyzed nanocomposites

    Mechanical and Shape-Memory Properties of Poly(mannitol sebacate)/Cellulose Nanocrystal Nanocomposites

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    "This is the peer reviewed version of the following article: Sonseca, Á., Camarero‐Espinosa, S., Peponi, L., Weder, C., Foster, E. J., Kenny, J. M., & Giménez, E. (2014). Mechanical and shape‐memory properties of poly (mannitol sebacate)/cellulose nanocrystal nanocomposites. Journal of Polymer Science Part A: Polymer Chemistry, 52(21), 3123-3133., which has been published in final form at https://doi.org/10.1002/pola.27367. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."[EN] Polyesters based on polyols and sebacic acid, known as poly(polyol sebacate)s (PPS), are attracting considerable attention, as their properties are potentially useful in the context of soft-tissue engineering applications. To overcome the drawback that PPSs generally display rather low strength and stiffness, we have pursued the preparation of nano composites based poly(mannitol sebacate) (PMS), a prominent example of this materials family, with cellulose nanocrystals (CNCs). Nanocomposites were achieved in a two-step process. A soluble, low-molecular-weight PMS pre-polymer was formed via the polycondensation reaction between sebacic acid and D-mannitol. Nanocomposites with different CNC content were prepared by solution-casting and curing under vacuum using two different profiles designed to prepare materials with low and high degree of crosslinking. The as-prepared nano composites have higher stiffness and toughness than the neat PMS matrix while maintaining a high elongation at break. A highly crosslinked nanocomposite with a CNC content of 5 wt % displays a sixfold increase in Young s modulus and a fivefold improvement in toughness. Nanocomposites also exhibit a shape memory effect with a switch temperature in the range of 15 to 45 C; in particular the materials with a thermal transition in the upper part of this range are potentially useful for biomedical applicationsThe authors gratefully acknowledge financial support received from Spanish Ministry of Economy and Competitiveness (Project MAT2010/21494-C03), as well as the support of FPU grant from MED (MED-FPU; AP2009-2482), JAE-Doc grant (CSIC co-financed by FSE), Swiss National Science foundation (National Research Programme 64, Project #406440_131264/1) and the Adolphe Merkle Foundation.Sonseca, A.; Camarero-Espinosa, S.; Peponi, L.; Weder, C.; Foster, E.; Kenny, JM.; Giménez Torres, E. (2014). Mechanical and Shape-Memory Properties of Poly(mannitol sebacate)/Cellulose Nanocrystal Nanocomposites. Journal of Polymer Science Part A Polymer Chemistry. 52(21):3123-3133. https://doi.org/10.1002/pola.27367S312331335221Bruggeman, J. P., de Bruin, B.-J., Bettinger, C. J., & Langer, R. (2008). Biodegradable poly(polyol sebacate) polymers. Biomaterials, 29(36), 4726-4735. doi:10.1016/j.biomaterials.2008.08.037Li, Y., Thouas, G. A., & Chen, Q.-Z. (2012). Biodegradable soft elastomers: synthesis/properties of materials and fabrication of scaffolds. RSC Advances, 2(22), 8229. doi:10.1039/c2ra20736bYang, J., Webb, A. R., Pickerill, S. J., Hageman, G., & Ameer, G. A. (2006). Synthesis and evaluation of poly(diol citrate) biodegradable elastomers. Biomaterials, 27(9), 1889-1898. doi:10.1016/j.biomaterials.2005.05.106Yang, J., Webb, A. R., & Ameer, G. A. (2004). Novel Citric Acid-Based Biodegradable Elastomers for Tissue Engineering. Advanced Materials, 16(6), 511-516. doi:10.1002/adma.200306264Park, H., Seo, J., Lee, H.-Y., Kim, H.-W., Wall, I. B., Gong, M.-S., & Knowles, J. C. (2012). Synthesis of elastic biodegradable polyesters of ethylene glycol and butylene glycol from sebacic acid. Acta Biomaterialia, 8(8), 2911-2918. doi:10.1016/j.actbio.2012.04.026Sun, Z.-J., Wu, L., Lu, X.-L., Meng, Z.-X., Zheng, Y.-F., & Dong, D.-L. (2008). The characterization of mechanical and surface properties of poly (glycerol–sebacate–lactic acid) during degradation in phosphate buffered saline. Applied Surface Science, 255(2), 350-352. doi:10.1016/j.apsusc.2008.06.157Liu, Q., Tan, T., Weng, J., & Zhang, L. (2009). Study on the control of the compositions and properties of a biodegradable polyester elastomer. Biomedical Materials, 4(2), 025015. doi:10.1088/1748-6041/4/2/025015SUNDBACK, C., SHYU, J., WANG, Y., FAQUIN, W., LANGER, R., VACANTI, J., & HADLOCK, T. (2005). Biocompatibility analysis of poly(glycerol sebacate) as a nerve guide material. Biomaterials, 26(27), 5454-5464. doi:10.1016/j.biomaterials.2005.02.004Sun, Z.-J., Chen, C., Sun, M.-Z., Ai, C.-H., Lu, X.-L., Zheng, Y.-F., … Dong, D.-L. (2009). The application of poly (glycerol–sebacate) as biodegradable drug carrier. Biomaterials, 30(28), 5209-5214. doi:10.1016/j.biomaterials.2009.06.007Mahdavi, A., Ferreira, L., Sundback, C., Nichol, J. W., Chan, E. P., Carter, D. J. D., … Karp, J. M. (2008). A biodegradable and biocompatible gecko-inspired tissue adhesive. Proceedings of the National Academy of Sciences, 105(7), 2307-2312. doi:10.1073/pnas.0712117105Motlagh, D., Yang, J., Lui, K. Y., Webb, A. R., & Ameer, G. A. (2006). Hemocompatibility evaluation of poly(glycerol-sebacate) in vitro for vascular tissue engineering. Biomaterials, 27(24), 4315-4324. doi:10.1016/j.biomaterials.2006.04.010Wang, Y., Ameer, G. A., Sheppard, B. J., & Langer, R. (2002). A tough biodegradable elastomer. Nature Biotechnology, 20(6), 602-606. doi:10.1038/nbt0602-602Jaafar, I. H., Ammar, M. M., Jedlicka, S. S., Pearson, R. A., & Coulter, J. P. (2010). Spectroscopic evaluation, thermal, and thermomechanical characterization of poly(glycerol-sebacate) with variations in curing temperatures and durations. Journal of Materials Science, 45(9), 2525-2529. doi:10.1007/s10853-010-4259-0Chen, Q.-Z., Bismarck, A., Hansen, U., Junaid, S., Tran, M. Q., Harding, S. E., … Boccaccini, A. R. (2008). Characterisation of a soft elastomer poly(glycerol sebacate) designed to match the mechanical properties of myocardial tissue. Biomaterials, 29(1), 47-57. doi:10.1016/j.biomaterials.2007.09.010Liang, S.-L., Cook, W. D., Thouas, G. A., & Chen, Q.-Z. (2010). The mechanical characteristics and in vitro biocompatibility of poly(glycerol sebacate)-Bioglass® elastomeric composites. Biomaterials, 31(33), 8516-8529. doi:10.1016/j.biomaterials.2010.07.105Meyers, M. A., Chen, P.-Y., Lin, A. Y.-M., & Seki, Y. (2008). Biological materials: Structure and mechanical properties. Progress in Materials Science, 53(1), 1-206. doi:10.1016/j.pmatsci.2007.05.002Sastri, V. R. (2010). Other Polymers. Plastics in Medical Devices, 217-262. doi:10.1016/b978-0-8155-2027-6.10009-1Chen, Q.-Z., Liang, S.-L., Wang, J., & Simon, G. P. (2011). Manipulation of mechanical compliance of elastomeric PGS by incorporation of halloysite nanotubes for soft tissue engineering applications. Journal of the Mechanical Behavior of Biomedical Materials, 4(8), 1805-1818. doi:10.1016/j.jmbbm.2011.05.038Liu, Q., Wu, J., Tan, T., Zhang, L., Chen, D., & Tian, W. (2009). Preparation, properties and cytotoxicity evaluation of a biodegradable polyester elastomer composite. Polymer Degradation and Stability, 94(9), 1427-1435. doi:10.1016/j.polymdegradstab.2009.05.023Chen, Q., Jin, L., Cook, W. D., Mohn, D., Lagerqvist, E. L., Elliott, D. A., … Elefanty, A. G. (2010). Elastomeric nanocomposites as cell delivery vehicles and cardiac support devices. Soft Matter, 6(19), 4715. doi:10.1039/c0sm00213eEichhorn, S. J., Dufresne, A., Aranguren, M., Marcovich, N. E., Capadona, J. R., Rowan, S. J., … Peijs, T. (2010). Review: current international research into cellulose nanofibres and nanocomposites. Journal of Materials Science, 45(1), 1-33. doi:10.1007/s10853-009-3874-0Clift, M. J. D., Foster, E. J., Vanhecke, D., Studer, D., Wick, P., Gehr, P., … Weder, C. (2011). Investigating the Interaction of Cellulose Nanofibers Derived from Cotton with a Sophisticated 3D Human Lung Cell Coculture. Biomacromolecules, 12(10), 3666-3673. doi:10.1021/bm200865jMendez, J., Annamalai, P. K., Eichhorn, S. J., Rusli, R., Rowan, S. J., Foster, E. J., & Weder, C. (2011). Bioinspired Mechanically Adaptive Polymer Nanocomposites with Water-Activated Shape-Memory Effect. Macromolecules, 44(17), 6827-6835. doi:10.1021/ma201502kHsu, L., Weder, C., & Rowan, S. J. (2011). Stimuli-responsive, mechanically-adaptive polymer nanocomposites. J. Mater. Chem., 21(9), 2812-2822. doi:10.1039/c0jm02383cAzizi Samir, M. A. S., Alloin, F., Sanchez, J.-Y., & Dufresne, A. (2004). Cross-Linked Nanocomposite Polymer Electrolytes Reinforced with Cellulose Whiskers. Macromolecules, 37(13), 4839-4844. doi:10.1021/ma049504yGoetz, L., Foston, M., Mathew, A. P., Oksman, K., & Ragauskas, A. J. (2010). Poly(methyl vinyl ether-co-maleic acid)−Polyethylene Glycol Nanocomposites Cross-Linked In Situ with Cellulose Nanowhiskers. Biomacromolecules, 11(10), 2660-2666. doi:10.1021/bm1006695Rusli, R., & Eichhorn, S. J. (2008). Determination of the stiffness of cellulose nanowhiskers and the fiber-matrix interface in a nanocomposite using Raman spectroscopy. Applied Physics Letters, 93(3), 033111. doi:10.1063/1.2963491Šturcová, A., Davies, G. R., & Eichhorn, S. J. (2005). Elastic Modulus and Stress-Transfer Properties of Tunicate Cellulose Whiskers. Biomacromolecules, 6(2), 1055-1061. doi:10.1021/bm049291kDe Souza Lima, M. M., Wong, J. T., Paillet, M., Borsali, R., & Pecora, R. (2003). Translational and Rotational Dynamics of Rodlike Cellulose Whiskers. Langmuir, 19(1), 24-29. doi:10.1021/la020475zSun, C. (Calvin). (2005). True Density of Microcrystalline Cellulose. Journal of Pharmaceutical Sciences, 94(10), 2132-2134. doi:10.1002/jps.20459Kokubo, T., Kim, H.-M., & Kawashita, M. (2003). Novel bioactive materials with different mechanical properties. Biomaterials, 24(13), 2161-2175. doi:10.1016/s0142-9612(03)00044-9Bellantone, M., Williams, H. D., & Hench, L. L. (2002). Broad-Spectrum Bactericidal Activity of Ag2O-Doped Bioactive Glass. Antimicrobial Agents and Chemotherapy, 46(6), 1940-1945. doi:10.1128/aac.46.6.1940-1945.2002Lecouvet, B., Horion, J., D’Haese, C., Bailly, C., & Nysten, B. (2013). Elastic modulus of halloysite nanotubes. Nanotechnology, 24(10), 105704. doi:10.1088/0957-4484/24/10/105704Prashantha, K., Lacrampe, M. F., & Krawczak, P. (2011). Processing and characterization of halloysite nanotubes filled polypropylene nanocomposites based on a masterbatch route: effect of halloysites treatment on structural and mechanical properties. Express Polymer Letters, 5(4), 295-307. doi:10.3144/expresspolymlett.2011.30Yakobson, B. I., & Avouris, P. (s. f.). Mechanical Properties of Carbon Nanotubes. Carbon Nanotubes, 287-327. doi:10.1007/3-540-39947-x_12Lu, Q., Keskar, G., Ciocan, R., Rao, R., Mathur, R. B., Rao, A. M., & Larcom, L. L. (2006). Determination of Carbon Nanotube Density by Gradient Sedimentation. The Journal of Physical Chemistry B, 110(48), 24371-24376. doi:10.1021/jp063660kGardner, D. J., Oporto, G. S., Mills, R., & Samir, M. A. S. A. (2008). Adhesion and Surface Issues in Cellulose and Nanocellulose. Journal of Adhesion Science and Technology, 22(5-6), 545-567. doi:10.1163/156856108x295509Koerner, H., Price, G., Pearce, N. A., Alexander, M., & Vaia, R. A. (2004). Remotely actuated polymer nanocomposites—stress-recovery of carbon-nanotube-filled thermoplastic elastomers. Nature Materials, 3(2), 115-120. doi:10.1038/nmat1059Capadona, J. R., Van Den Berg, O., Capadona, L. A., Schroeter, M., Rowan, S. J., Tyler, D. J., & Weder, C. (2007). A versatile approach for the processing of polymer nanocomposites with self-assembled nanofibre templates. Nature Nanotechnology, 2(12), 765-769. doi:10.1038/nnano.2007.379Dong, X. M., Kimura, T., Revol, J.-F., & Gray, D. G. (1996). Effects of Ionic Strength on the Isotropic−Chiral Nematic Phase Transition of Suspensions of Cellulose Crystallites. Langmuir, 12(8), 2076-2082. doi:10.1021/la950133bBraun, B., & Dorgan, J. R. (2009). Single-Step Method for the Isolation and Surface Functionalization of Cellulosic Nanowhiskers. Biomacromolecules, 10(2), 334-341. doi:10.1021/bm8011117Camarero Espinosa, S., Kuhnt, T., Foster, E. J., & Weder, C. (2013). Isolation of Thermally Stable Cellulose Nanocrystals by Phosphoric Acid Hydrolysis. Biomacromolecules, 14(4), 1223-1230. doi:10.1021/bm400219uLe Cam, E., Frechon, D., Barray, M., Fourcade, A., & Delain, E. (1994). Observation of binding and polymerization of Fur repressor onto operator-containing DNA with electron and atomic force microscopes. Proceedings of the National Academy of Sciences, 91(25), 11816-11820. doi:10.1073/pnas.91.25.11816Behl, M., & Lendlein, A. (2007). Shape-memory polymers. Materials Today, 10(4), 20-28. doi:10.1016/s1369-7021(07)70047-0Wagermaier, W., Kratz, K., Heuchel, M., & Lendlein, A. (2009). Characterization Methods for Shape-Memory Polymers. Advances in Polymer Science, 97-145. doi:10.1007/12_2009_25Ratna, D., & Karger-Kocsis, J. (2007). Recent advances in shape memory polymers and composites: a review. Journal of Materials Science, 43(1), 254-269. doi:10.1007/s10853-007-2176-7Yakacki, C. M., & Gall, K. (2009). Shape-Memory Polymers for Biomedical Applications. Advances in Polymer Science, 147-175. doi:10.1007/12_2009_23Maliger, R., Halley, P. J., & Cooper-White, J. J. (2012). Poly(glycerol-sebacate) bioelastomers-kinetics of step-growth reactions using Fourier Transform (FT)-Raman spectroscopy. Journal of Applied Polymer Science, 127(5), 3980-3986. doi:10.1002/app.37719Chen, Q. (2012). Poly(Polyol Sebacate)-Based Elastomeric Nanobiomaterials for Soft Tissue Engineering. Biomedical Materials and Diagnostic Devices, 529-560. doi:10.1002/9781118523025.ch17Filpponen, I., & Argyropoulos, D. S. (2008). Determination of Cellulose Reactivity by Using Phosphitylation and Quantitative31P NMR Spectroscopy. Industrial & Engineering Chemistry Research, 47(22), 8906-8910. doi:10.1021/ie800936xPatel, A., Gaharwar, A. K., Iviglia, G., Zhang, H., Mukundan, S., Mihaila, S. M., … Khademhosseini, A. (2013). Highly elastomeric poly(glycerol sebacate)-co-poly(ethylene glycol) amphiphilic block copolymers. Biomaterials, 34(16), 3970-3983. doi:10.1016/j.biomaterials.2013.01.045Pei, A., Malho, J.-M., Ruokolainen, J., Zhou, Q., & Berglund, L. A. (2011). Strong Nanocomposite Reinforcement Effects in Polyurethane Elastomer with Low Volume Fraction of Cellulose Nanocrystals. Macromolecules, 44(11), 4422-4427. doi:10.1021/ma200318kTien, Y. I., & Wei, K. H. (2001). High-Tensile-Property Layered Silicates/Polyurethane Nanocomposites by Using Reactive Silicates as Pseudo Chain Extenders. Macromolecules, 34(26), 9045-9052. doi:10.1021/ma010551pHood, M. A., Gold, C. S., Beyer, F. L., Sands, J. M., & Li, C. Y. (2013). Extraordinarily high plastic deformation in polyurethane/silica nanoparticle nanocomposites with low filler concentrations. Polymer, 54(24), 6510-6515. doi:10.1016/j.polymer.2013.10.010Shanmuganathan, K., Capadona, J. R., Rowan, S. J., & Weder, C. (2010). Bio-inspired mechanically-adaptive nanocomposites derived from cotton cellulose whiskers. J. Mater. Chem., 20(1), 180-186. doi:10.1039/b916130aAbdullah, S. A., Jumahat, A., Abdullah, N. R., & Frormann, L. (2012). Determination of Shape Fixity and Shape Recovery Rate of Carbon Nanotube-filled Shape Memory Polymer Nanocomposites. Procedia Engineering, 41, 1641-1646. doi:10.1016/j.proeng.2012.07.362Nelson, B. A., King, W. P., & Gall, K. (2005). Shape recovery of nanoscale imprints in a thermoset «shape memory» polymer. Applied Physics Letters, 86(10), 103108. doi:10.1063/1.1868883Meng, Q., Hu, J., & Zhu, Y. (2007). Shape-memory polyurethane/multiwalled carbon nanotube fibers. Journal of Applied Polymer Science, 106(2), 837-848. doi:10.1002/app.2651

    Clinical translation of [18F]ICMT-11 for measuring chemotherapy-induced caspase 3/7 activation in breast and lung cancer

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    Background: Effective anticancer therapy is thought to involve induction of tumour cell death through apoptosis and/or necrosis. [18F]ICMT-11, an isatin sulfonamide caspase-3/7-specific radiotracer, has been developed for PET imaging and shown to have favourable dosimetry, safety, and biodistribution. We report the translation of [18F]ICMT-11 PET to measure chemotherapy-induced caspase-3/7 activation in breast and lung cancer patients receiving first-line therapy. Results: Breast tumour SUVmax of [18F]ICMT-11 was low at baseline and unchanged following therapy. Measurement of M30/M60 cytokeratin-18 cleavage products showed that therapy was predominantly not apoptosis in nature. While increases in caspase-3 staining on breast histology were seen, post-treatment caspase-3 positivity values were only approximately 1%; this low level of caspase-3 could have limited sensitive detection by [18F]ICMT-11-PET. Fourteen out of 15 breast cancer patients responded to first–line chemotherapy (complete or partial response); one patient had stable disease. Four patients showed increases in regions of high tumour [18F]ICMT-11 intensity on voxel-wise analysis of tumour data (classed as PADS); response was not exclusive to patients with this phenotype. In patients with lung cancer, multi-parametric [18F]ICMT-11 PET and MRI (diffusion-weighted- and dynamic contrast enhanced-MRI) showed that PET changes were concordant with cell death in the absence of significant perfusion changes. Conclusion: This study highlights the potential use of [18F]ICMT-11 PET as a promising candidate for non-invasive imaging of caspase3/7 activation, and the difficulties encountered in assessing early-treatment responses. We summarize that tumour response could occur in the absence of predominant chemotherapy-induced caspase-3/7 activation measured non-invasively across entire tumour lesions in patients with breast and lung cancer

    Cadenas ligeras libres en suero en el diagnóstico de Gammapatías Monoclonales

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    Monoclonal gammopathies are a group of diseases caused by the clonal proliferation of plasma cells that secrete the same type of immunoglobulin, known as clonal immunoglobulin. The prognosis of these hematological diseases depends on the early diagnosis, in Multiple Myeloma is associated with a less serious disease. Laboratory tests play an important role in the different stages of clinical management of patients with Monoclonal gammopathies, including traditional tests such as serum protein electrophoresis, immunofixation, and the determination of free light chains in serum it is considered an important complementary test since it allows initially to show the presence of Monoclonal gammopathies in an early way due to its high sensitivity, likewise it allows to quantify the kappa / lambda free light chains and to determine the monoclonality through the respective quotient, this is a parameter that since 2014 is integrated into the myeloma diagnostic criteria according to the International Myeloma Working Group.As a methodology, the search of bibliographic material was carried out: the keywords were defined using the DeCS and MeSH descriptors, the search for information in the PubMed, ScienceDirect bibliographic databases was started and an internet search was carried out with the “google academic” search engine with the same terms. Those articles and internet pages that had information of interest, that met the requirements to be included in the review article, were stored in a database and finally the critical reading of the information was selected.Las gammapatías monoclonales son un conjunto de enfermedades causadas por la proliferación clonal de células plasmáticas que secretan un mismo tipo de inmunoglobulina, conocido como inmunoglobulina clonal. El pronóstico de estas enfermedades hematológicas depende del diagnóstico temprano, en el Mieloma Múltiple se asocia con una enfermedad menos grave. Las pruebas de laboratorio desempeñan un papel importante en las distintas etapas del manejo clínico del paciente con gammapatía monoclonal. Estas incluyen pruebas tradicionales como la electroforesis de proteínas en suero, la inmunofijación, y actualmente se adiciona la determinación de cadenas ligeras libres en suero, una prueba complementaria importante porque permite evidenciar la presencia de gammapatías monoclonales de forma temprana por su alta sensibilidad, así como cuantificar las cadenas ligeras libres kappa/lambda y determinar la monoclonalidad a través del respectivo cociente, parámetro que desde el 2014 está integrado en los criterios diagnósticos de mieloma según la International Myeloma Working Group.Como metodología se realizó la búsqueda de material bibliográfico: se definieron las palabras clave utilizando los descriptores DeCS y MeSH, se inició la búsqueda de información en las bases de datos bibliográficas PubMed, ScienceDirect y se ejecutó una búsqueda en internet con buscador “google académico” con los mismos términos. Se seleccionaron aquellos artículos y páginas de internet que contaran con información de interés, que cumplieran los requisitos para incluirse dentro del artículo de revisión, se almacenaron en una base de datos y finalmente se realizó la lectura crítica de la información

    P2X7 Receptor-Dependent microRNA Expression Profile in the Brain Following Status Epilepticus in Mice

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    The ionotropic ATP-gated P2X7 receptor is an important contributor to inflammatory signaling cascadesviathe release of Interleukin-1 beta, as well as having roles in cell death, neuronal plasticity and the release of neurotransmitters. Accordingly, there is interest in targeting the P2X7 receptor for the treatment of epilepsy. However, the signaling pathways downstream of P2X7 receptor activation remain incompletely understood. Notably, recent studies showed that P2X7 receptor expression is controlled, in part, by microRNAs (miRNAs). Here, we explored P2X7 receptor-dependent microRNA expression by comparing microRNA expression profiles of wild-type (wt) and P2X7 receptor knockout mice before and after status epilepticus. Genome-wide microRNA profiling was performed using hippocampi from wt and P2X7 receptor knockout mice following status epilepticus induced by intra-amygdala kainic acid. This revealed that the genetic deletion of the P2X7 receptor results in distinct patterns of microRNA expression. Specifically, we found that in vehicle-injected control mice, the lack of the P2X7 receptor resulted in the up-regulation of 50 microRNAs and down-regulation of 35 microRNAs. Post-status epilepticus, P2X7 receptor deficiency led to the up-regulation of 44 microRNAs while 13 microRNAs were down-regulated. Moreover, there was only limited overlap among identified P2X7 receptor-dependent microRNAs between control conditions and post-status epilepticus, suggesting that the P2X7 receptor regulates the expression of different microRNAs during normal physiology and pathology. Bioinformatic analysis revealed that genes targeted by P2X7 receptor-dependent microRNAs were particularly overrepresented in pathways involved in intracellular signaling, inflammation, and cell death;processes that have been repeatedly associated with P2X7 receptor activation. Moreover, whereas genes involved in signaling pathways and inflammation were common among up- and down-regulated P2X7 receptor-dependent microRNAs during physiological and pathological conditions, genes associated with cell death seemed to be restricted to up-regulated microRNAs during both physiological conditions and post-status epilepticus. Taken together, our results demonstrate that the P2X7 receptor impacts on the expression profile of microRNAs in the brain, thereby possibly contributing to both the maintenance of normal cellular homeostasis and pathological processes

    Second trimester inflammatory and metabolic markers in women delivering preterm with and without preeclampsia.

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    ObjectiveInflammatory and metabolic pathways are implicated in preterm birth and preeclampsia. However, studies rarely compare second trimester inflammatory and metabolic markers between women who deliver preterm with and without preeclampsia.Study designA sample of 129 women (43 with preeclampsia) with preterm delivery was obtained from an existing population-based birth cohort. Banked second trimester serum samples were assayed for 267 inflammatory and metabolic markers. Backwards-stepwise logistic regression models were used to calculate odds ratios.ResultsHigher 5-α-pregnan-3β,20α-diol disulfate, and lower 1-linoleoylglycerophosphoethanolamine and octadecanedioate, predicted increased odds of preeclampsia.ConclusionsAmong women with preterm births, those who developed preeclampsia differed with respect metabolic markers. These findings point to potential etiologic underpinnings for preeclampsia as a precursor to preterm birth

    Differential Effects of Pergolide and Bromocriptine on Working Memory Performance and Brain Activation after Mild Traumatic Brain Injury

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    Dopamine D1 and D2 receptors differ with respect to patterns of regional brain distribution and behavioral effects. Pre-clinical work suggests that D1 agonists enhance working memory, but the absence of selective D1 agonists has constrained using this approach in humans. This study examines working memory performance in mild traumatic brain injury (mTBI) patients when given pergolide, a mixed D1/D2 agonist, compared with bromocriptine, a selective D2 agonist. Fifteen individuals were studied 1 month after mTBI and compared with 17 healthy controls. At separate visits, participants were administered 1.25 mg bromocriptine or 0.05 mg pergolide prior to functional magnetic resonance imaging (MRI) using a working memory task (visual-verbal n-back). Results indicated a significant group-by-drug interaction for mean performance across n-back task conditions, where the mTBI group showed better performance on pergolide relative to bromocriptine, whereas controls showed the opposite pattern. There was also a significant effect of diagnosis, where mTBI patients performed worse than controls, particularly while on bromocriptine, as shown in our prior work. Functional MRI activation during the most challenging task condition (3-back > 0-back contrast) showed a significant group-by-drug interaction, with the mTBI group showing increased activation relative to controls in working memory circuitry while on pergolide, including in the left inferior frontal gyrus. Across participants there was a positive correlation between change in activation in this region and change in performance between drug conditions. Results suggest that activation of the D1 receptor may improve working memory performance after mTBI. This has implications for the development of pharmacological strategies to treat cognitive deficits after mTBI

    'To live and die [for] Dixie': Irish civilians and the Confederate States of America

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    Around 20,000 Irishmen served in the Confederate army in the Civil War. As a result, they left behind, in various Southern towns and cities, large numbers of friends, family, and community leaders. As with native-born Confederates, Irish civilian support was crucial to Irish participation in the Confederate military effort. Also, Irish civilians served in various supporting roles: in factories and hospitals, on railroads and diplomatic missions, and as boosters for the cause. They also, however, suffered in bombardments, sieges, and the blockade. Usually poorer than their native neighbours, they could not afford to become 'refugees' and move away from the centres of conflict. This essay, based on research from manuscript collections, contemporary newspapers, British Consular records, and Federal military records, will examine the role of Irish civilians in the Confederacy, and assess the role this activity had on their integration into Southern communities. It will also look at Irish civilians in the defeat of the Confederacy, particularly when they came under Union occupation. Initial research shows that Irish civilians were not as upset as other whites in the South about Union victory. They welcomed a return to normalcy, and often 'collaborated' with Union authorities. Also, Irish desertion rates in the Confederate army were particularly high, and I will attempt to gauge whether Irish civilians played a role in this. All of the research in this paper will thus be put in the context of the Drew Gilpin Faust/Gary Gallagher debate on the influence of the Confederate homefront on military performance. By studying the Irish civilian experience one can assess how strong the Confederate national experiment was. Was it a nation without a nationalism
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