Restricción de crecimiento intrauterino

ResumenLa restricción del crecimiento intrauterino es una importante causa de morbilidad y mortalidad perinatal, con consecuencias que pueden tener implicancias hasta en la vida adulta. No existen estrategias terapéuticas a la fecha por lo que, su manejo consiste principalmente en su diagnóstico y seguimiento para definir el momento de finalizar el embarazo, equilibrando los riesgos de prematurez con la morbimortalidad esperada para cada condición fetal. En el presente artículo se describen las claves del diagnóstico, clasificación y seguimiento de acuerdo a estándares actuales que permitan el adecuado manejo clínico.SummaryIntrauterine growth restriction is a major cause of perinatal morbidity and mortality with consequences that may have implications even in adulthood. No treatment have currently available, so, management is mainly based in diagnosis and monitoring in order to choose the right time to delivery, balancing the risks of prematurity with the expected morbidity and mortality. A precise diagnosis, classification and fetal surveillance according to current standards is discussed

Nuevos modelos multicelulares para la predicción de la hepatotoxicidad idiosincrática

La hepatotoxicidad inducida por fármacos (DILI) se refiere al daño hepático resultante de la exposición del organismo a un medicamento o xenobiótico. Concretamente la de tipo idiosincrático (iDILI) es la principal causa de retirada de fármacos tanto en fases de desarrollo como ya comercializados. Los estudios preclínicos con animales de experimentación presentan una baja predictividad, por ello, ha sido necesaria la búsqueda de nuevos modelos in vitro que permitan una mejor comprensión de los mecanismos que subyacen al iDILI para reducir su impacto. La mayoría de los modelos clásicos propuestos están basados en el cultivo de hepatocitos, pero no permiten modelar sus interacciones con las células no parenquimáticas como las células de Kupffer, que han demostrado estar implicadas en la hepatotoxicidad mediada por el sistema inmunitario. En el presente trabajo se ha optimizado y caracterizado un modelo de co-cultivo de hepatocitos y macrófagos proinflamatorios, derivados de líneas celulares inmortalizadas (HepG2 y THP-1, respectivamente) para el estudio de la hepatotoxicidad idiosincrática. El modelo ha mostrado un adecuado mantenimiento de la viabilidad celular, expresión génica y funcionalidad hepática. Asimismo, la idoneidad del co-cultivo como plataforma de detección de fármacos que inducen iDILI ha sido evaluada a través de su exposición a dos medicamentos asociados con este, el trovafloxacino y la troglitazona. Los resultados obtenidos han probado su mayor sensibilidad y activación de las rutas metabólicas que conducen al iDILI, frente a los sistemas de monocultivo utilizados tradicionalmente.A los comités organizadores del CASEIB por proporcionar las guías para la realización del presente documento

Non invasive ventilation after extubation in paediatric patients: a preliminary study

<p>Abstract</p> <p>Background</p> <p>Non-invasive ventilation (NIV) may be useful after extubation in children. Our objective was to determine postextubation NIV characteristics and to identify risk factors of postextubation NIV failure.</p> <p>Methods</p> <p>A prospective observational study was conducted in an 8-bed pediatric intensive care unit (PICU). Following PICU protocol, NIV was applied to patients who had been mechanically ventilated for over 12 hours considered at high-risk of extubation failure -elective NIV (eNIV), immediately after extubation- or those who developed respiratory failure within 48 hours after extubation -rescue NIV (rNIV)-. Patients were categorized in subgroups according to their main underlying conditions. NIV was deemed successful when reintubation was avoided. Logistic regression analysis was performed in order to identify predictors of NIV failure.</p> <p>Results</p> <p>There were 41 episodes (rNIV in 20 episodes). Success rate was 50% in rNIV and 81% in eNIV (p = 0.037). We found significant differences in univariate analysis between success and failure groups in respiratory rate (RR) decrease at 6 hours, FiO₂at 1 hour and PO₂/FiO₂ratio at 6 hours. Neurologic condition was found to be associated with NIV failure. Multiple logistic regression analysis identified no variable as independent NIV outcome predictor.</p> <p>Conclusions</p> <p>Our data suggest that postextubation NIV seems to be useful in avoiding reintubation in high-risk children when applied immediately after extubation. NIV was more likely to fail when ARF has already developed (rNIV), when RR at 6 hours did not decrease and if oxygen requirements increased. Neurologic patients seem to be at higher risk of reintubation despite NIV use.</p

Reversal of economic fortunes: institutions and the changing ascendancy of Barcelona and Madrid as economic hubs

This paper looks at the divergent economic trajectories of Barcelona and Madrid since Spain's transition to democracy. It highlights how Barcelona, the city that was better positioned four decades ago to emerge as the main Spanish economic hub, has lost out to Madrid. We argue that the contrasting trajectories of the two cities have less to do with the pull of Madrid as the capital of Spain, with the development of new infrastructure in the country, or with agglomeration economies, and more with institutional factors. A growing societal divide in Barcelona along economic, social, and identity lines has led to a greater breakdown of trust and to the development of strong groups with limited capacity to bridge with one another than in Madrid. This has entailed the emergence of negative externalities that have limited the economic potential for growth in Barcelona and facilitated the rise of Madrid as the main economic hub within Spain

A pathogenic role for germline PTEN variants which accumulate into the nucleus.

The PTEN gene encodes a master regulator protein that exerts essential functions both in the cytoplasm and in the nucleus. PTEN is mutated in the germline of both patients with heterogeneous tumor syndromic diseases, categorized as PTEN hamartoma tumor syndrome (PHTS), and a group affected with autism spectrum disorders (ASD). Previous studies have unveiled the functional heterogeneity of PTEN variants found in both patient cohorts, making functional studies necessary to provide mechanistic insights related to their pathogenicity. Here, we have functionally characterized a PTEN missense variant [c.49C>G; p.(Gln17Glu); Q17E] associated to both PHTS and ASD patients. The PTEN Q17E variant displayed partially reduced PIP3-catalytic activity and normal stability in cells, as shown using S. cerevisiae and mammalian cell experimental models. Remarkably, PTEN Q17E accumulated in the nucleus, in a process involving the PTEN N-terminal nuclear localization sequence. The analysis of additional germline-associated PTEN N-terminal variants illustrated the existence of a PTEN N-terminal region whose targeting in disease causes PTEN nuclear accumulation, in parallel with defects in PIP3-catalytic activity in cells. Our findings highlight the frequent occurrence of PTEN gene mutations targeting PTEN N-terminus whose pathogenicity may be related, at least in part, with the retention of PTEN in the nucleus. This could be important for the implementation of precision therapies for patients with alterations in the PTEN pathway

Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites

The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions. The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that the wood in the starch composites did not prevent water loss from the samples.Peer reviewe

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

The Helicobacter pylori Genome Project : insights into H. pylori population structure from analysis of a worldwide collection of complete genomes

Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics