40 research outputs found

    Michael von Albrecht. Ovidio. Una introducción. Murcia, Editorial de la Universidad de Murcia – Editum, 2015, 475 pp.

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    Fil: Sala, María Elisa. Universidad Nacional de Tucumá

    α-Galactosidase-A Loaded-Nanoliposomes with Enhanced Enzymatic Activity and Intracellular Penetration

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    Lysosomal storage disorders (LSD) are caused by lysosomal dysfunction usually as a consequence of deficiency of a single enzyme required for the metabolism of macromolecules, such as lipids, glycoproteins, and mucopolysaccharides. For instance, the lack of α-galactosidase A (GLA) activity in Fabry disease patients causes the accumulation of glycosphingolipids in the vasculature leading to multiple organ pathology. Enzyme replacement therapy, which is the most common treatment of LSD, exhibits several drawbacks mainly related to the instability and low efficacy of the exogenously administered therapeutic enzyme. In this work, the unprecedented increased enzymatic activity and intracellular penetration achieved by the association of a human recombinant GLA to nanoliposomes functionalized with Arginine-Glycine-Aspartic acid (RGD) peptides is reported. Moreover, these new GLA loaded nanoliposomes lead to a higher efficacy in the reduction of the GLA substrate named globotriasylceramide in a cellular model of Fabry disease, than that achieved by the same concentration of the free enzyme. The preparation of these new liposomal formulations by DELOS-SUSP, based on the depressurization of a CO-expanded liquid organic solution, shows the great potential of this CO-based methodology for the one-step production of protein-nanoliposome conjugates as bioactive nanomaterials with therapeutic interest. α-galactosidase-A-(GLA)-loaded nano-liposomes functionalized with Arginine-Glycine-Aspartic acid (RGD) peptides are successfully prepared by using compressed CO. This nanoformulation shows an unprecedented increase of the GLA enzymatic activity and intracellular penetration, in comparison to the free enzyme. Moreover, these nanoconjugates lead to a higher efficacy in the reduction of the GLA substrate named globotriasylceramide (Gb3), in a cellular model of Fabry disease, than that achieved by the free enzyme.We acknowledge financial support from Instituto de Salud Carlos III, through “Acciones CIBER”. The Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) is an initiative funded by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. The authors appreciate the financial support through the “Development of nanomedicines for enzymatic replacement therapy in Fabry disease” project, granted by the Fundació Marató TV3, BE-WELL (CTQ2013-40480-R) project granted by DGI (Spain), GenCat (2014-SGR-17) project financed by DGR (Catalunya), LIPOCELL project financed by CIBER-BBN and Praxis Pharmaceuticals, TERARMET (RTC-2014-2207-1) project financed by MEC (Spain) and excellence Grant CTS-6270 financed by “Junta de Andalucía>. The authors wish also to thank the Microscopy Service of UAB, especially Pablo Castro for the technical support in taking the Cryo-TEM images, and Mª Eugenia López Sánchez and Natalia García Aranda for their technical assistance in the in vitro activity assays. AV is recipient of an ICREA Academia (Generalitat de Catalunya) award. We acknowledge EMBL and Electra synchrotrons for beamtime allocation, and H. Amenitsch, B. Marmilori and B. Sartori for technical support at the SAXS beamline. Access to the synchrotron facility is supported by the BioStructX program (nº BIOSTRUCTX_1093). We also acknowledge computer time at the Minotauro-BSC supercomputer from the Red Española de Supercomputación (RES).Peer Reviewe

    Different Plasma Markers of Inflammation Are Influenced by Immune Recovery and cART Composition or Intensification in Treated HIV Infected Individuals

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    BACKGROUND: HIV-1 infection increases plasma levels of inflammatory markers. Combination antiretroviral therapy (cART) does not restore inflammatory markers to normal levels. Since intensification of cART with raltegravir reduced CD8 T-cell activation in the Discor-Ral and IntegRal studies, we have evaluated the effect of raltegravir intensification on several soluble inflammation markers in these studies. METHODS: Longitudinal plasma samples (0-48 weeks) from the IntegRal (n = 67, 22 control and 45 intensified individuals) and the Discor-Ral studies (44 individuals with CD4 T-cell counts<350 cells/µl, 14 control and 30 intensified) were assayed for 25 markers. Mann-Whitney, Wilcoxon, Spearman test and linear mixed models were used for analysis. RESULTS: At baseline, different inflammatory markers were strongly associated with HCV co-infection, lower CD4 counts and with cART regimens (being higher in PI-treated individuals), but poorly correlated with detection of markers of residual viral replication. Although raltegravir intensification reduced inflammation in individuals with lower CD4 T-cell counts, no effect of intensification was observed on plasma markers of inflammation in a global analysis. An association was found, however, between reductions in immune activation and plasma levels of the coagulation marker D-dimer, which exclusively decreased in intensified patients on protease inhibitor (PI)-based cART regimens (P = 0.040). CONCLUSIONS: The inflammatory profile in treated HIV-infected individuals showed a complex association with HCV co-infection, the levels of CD4 T cells and the cART regimen. Raltegravir intensification specifically reduced D-dimer levels in PI-treated patients, highlighting the link between cART composition and residual viral replication; however, raltegravir had little effect on other inflammatory markers

    Transdisciplinary studies in socio-ecosystems: Theoretical considerations and its application in Latin American contexts

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    Debido a limitaciones para abordar la complejidad de la relación sociedad-naturaleza, los esfuerzos para solucionar los problemas ambientales han sido en general infructuosos. Aquí proponemos que el enfoque holístico de “socio-ecosistema” por parte de la academia, podría contribuir a disminuir estas limitaciones desde la adopción de cuatro cambios: i) ontológico, que presenta el concepto de “socio-ecosistemas”; ii) epistemológico, que propone a la transdisciplina como la forma de entenderlos, iii) metodológico, que sugiere intervenir en ellos de forma participativa y adaptativa y, iv) cambios institucionales que facilitarían la adopción de esta propuesta. Este planteamiento se complementa con la descripción de una experiencia transdiciplinaria en la cuenca del río San Juan Zitácuaro, México, en el contexto de un curso internacional de manejo de socio-ecosistemas.Given the difficulties to approach the complex relationship bettween society and nature, efforts to solve environmental problems have generally been unsuccessful. Here we suggest that a hollistic “socio-ecosystem” approach by the sciencies could help diminish these difficulties by embracing four kinds of changes: i) ontological, which introduces the concept of “socio-ecosystem”; ii) epistemological, which proposes transdiscipline as the way to understand them, iii) metholodogical, which suggests that in intervention in them must be participatory and adaptive, iv) institutional changes that would facilitate the adoption of this approach. This is then followed by a description of a transdisciplinary work experience in the Zitácuaro river basin, in Mexico, in the context of an international course on socio-ecosystem management.Fil: Ortega Uribe, Tamara. Universidad de Chile; ChileFil: Mastrangelo, Matias Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; ArgentinaFil: Villarroel Torrez, Daniel. Universidad de Buenos Aires. Facultad de Agronomía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Piaz, Agustín Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Humanidades. Centro de Estudios de Historia de la Ciencia y de la Técnica ; ArgentinaFil: Vallejos, María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; ArgentinaFil: Saenz Ceja, Jesús Eduardo. Universidad Nacional Autónoma de México. Centro de Investigaciones en Ecosistemas; MéxicoFil: Gallego, Federico. Universidad de la República. Facultad de Ciencias; UruguayFil: Franquesa Soler, Monserrat. Instituto de Ecología; MéxicoFil: Calzada Peña, Leonardo. Universidad Nacional Autónoma de México; MéxicoFil: Espinosa Mellado, Noelia. Universidad de la Armada; MéxicoFil: Fiestas Flores, Jerico. Instituto de Estudios Peruanos; PerúFil: Gill Mairhofer, Luis R.. Ministerio de la Defensa Pública; ParaguayFil: González Espino, Zarahí. Instituto Superior de Tecnologías y Ciencias Aplicadas. Facultad de Medio Ambiente. Departamento de Meteorología; CubaFil: Luna Salguero, Betsabé Montserrat. Sociedad de Historia Natural Niparajá; MéxicoFil: Martinez Peralta, Claudia María. Comisión de Ecología y Desarrollo Sustentable del Estado de Sonora. Dirección General de Conservación; MéxicoFil: Ochoa, Olivia. Universidad Nacional Autónoma de México; MéxicoFil: Pérez Volkow,Lucía. No especifica;Fil: Sala, Juan Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; ArgentinaFil: Sánchez Rose, Isabelle. Universidad Central de Venezuela; VenezuelaFil: Weeks, Madeline. University of Cambridge; Reino UnidoFil: Ávila García, Daniela. Universidad Nacional Autónoma de México; MéxicoFil: García Reyes, Isabel Bueno. Universidad Nacional Autónoma de México. Centro de Investigaciones en Ecosistemas; MéxicoFil: Carmona, Alejandra. Universidad Austral de Chile. Instituto de Economía Agraria; ChileFil: Castro Videla, Fernando Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Mendoza-San Juan; ArgentinaFil: Ferrer Gonzalez, César Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; ArgentinaFil: Frank Buss, María Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Pampa. Facultad de Agronomía; ArgentinaFil: López Carapia, Gabriela. Universidad Nacional Autónoma de México; MéxicoFil: Núñez Cruz, Martha. Universidad Nacional Autónoma de México; MéxicoFil: Taboada Hermoza, Rossi. Universidad Nacional Mayor de San Marcos; PerúFil: Benet, Daniel. Alternare A. C.; MéxicoFil: Venegas, Ysmael. Alternare A. C.; MéxicoFil: Balvanera, Patricia. Universidad Nacional Autónoma de México. Centro de Investigaciones en Ecosistemas; MéxicoFil: Mwampamba, Tuyeni H.. Universidad Nacional Autónoma de México. Centro de Investigaciones en Ecosistemas; MéxicoFil: Lazos Chavero, Elena. Universidad Nacional Autónoma de México. Centro de Investigaciones en Ecosistemas; MéxicoFil: Noellemeyer, Elke Johanna. Universidad Nacional de La Pampa. Facultad de Agronomía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Maass, Manuel. Universidad Nacional Autónoma de México. Centro de Investigaciones en Ecosistemas; Méxic

    Strategies to reengage patients lost to follow up in HIV care in high income countries, a scoping review

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    Background: Despite remarkable achievements in antiretroviral therapy (ART), losses to follow-up (LTFU) might prevent the long-term success of HIV treatment and might delay the achievement of the 90-90-90 objectives. This scoping review is aimed at the description and analysis of the strategies used in high-income countries to reengage LTFU in HIV care, their implementation and impact. Methods: A scoping review was done following Arksey & O'Malley's methodological framework and recommendations from Joanna Briggs Institute. Peer reviewed articles were searched for in Pubmed, Scopus and Web of Science; and grey literature was searched for in Google and other sources of information. Documents were charted according to the information presented on LTFU, the reengagement procedures used in HIV units in high-income countries, published during the last 15 years. In addition, bibliographies of chosen articles were reviewed for additional articles. Results: Twenty-eight documents were finally included, over 80% of them published in the United States later than 2015. Database searches, phone calls and/or mail contacts were the most common strategies used to locate and track LTFU, while motivational interviews and strengths-based techniques were used most often during reengagement visits. Outcomes like tracing activities efficacy, rates of reengagement and viral load reduction were reported as outcome measures. Conclusions: This review shows a recent and growing trend in developing and implementing patient reengagement strategies in HIV care. However, most of these strategies have been implemented in the United States and little information is available for other high-income countries. The procedures used to trace and contact LTFU are similar across reviewed studies, but their impact and sustainability are widely different depending on the country studied

    Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

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    The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

    Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19.

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    Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6+/-9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; pPeer reviewe

    La renovación de la palabra en el bicentenario de la Argentina : los colores de la mirada lingüística

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    El libro reúne trabajos en los que se exponen resultados de investigaciones presentadas por investigadores de Argentina, Chile, Brasil, España, Italia y Alemania en el XII Congreso de la Sociedad Argentina de Lingüística (SAL), Bicentenario: la renovación de la palabra, realizado en Mendoza, Argentina, entre el 6 y el 9 de abril de 2010. Las temáticas abordadas en los 167 capítulos muestran las grandes líneas de investigación que se desarrollan fundamentalmente en nuestro país, pero también en los otros países mencionados arriba, y señalan además las áreas que recién se inician, con poca tradición en nuestro país y que deberían fomentarse. Los trabajos aquí publicados se enmarcan dentro de las siguientes disciplinas y/o campos de investigación: Fonología, Sintaxis, Semántica y Pragmática, Lingüística Cognitiva, Análisis del Discurso, Psicolingüística, Adquisición de la Lengua, Sociolingüística y Dialectología, Didáctica de la lengua, Lingüística Aplicada, Lingüística Computacional, Historia de la Lengua y la Lingüística, Lenguas Aborígenes, Filosofía del Lenguaje, Lexicología y Terminología
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