Invasive and non-invasive methods to study inflammatory parameters in premature newborns with nrcrotizing enterocolitis

Introducción: La inflamación que acontece en el parto, mayor en el caso de la prematuridad, puede perdurar tras el nacimiento. Esto, unido a otros factores como la inmadurez del sistema inmunológico de la barrera intestinal puede hacer que estos recién nacidos sean susceptibles de presentar diversas enfermedades como la enterocolitis necrotizante (ECN), con una morbimortalidad muy elevada. El objetivo de este proyecto es profundizar en el conocimiento de la relación de la función de la barrera intestinal y la ECN a través del estudio de marcadores inflamatorios intestinales y sistémicos, realizando también una aproximación al conocimiento de las vías metabólicas implicadas en el desarrollo y regulación intestinal del recién nacido a través del estudio de miRNAs en muestras de leche materna de distintos grupos de recién nacidos. Metodología: Es un estudio observacional, descriptivo, analítico de casos y controles. Se establecieron tres grupos: un grupo de neonatos nacidos ≥37 semanas de edad gestacional (EG) con peso al nacer ≥ 2,500 g (grupo T), un grupo de neonatos prematuros nacidos antes de las 37 semanas de EG (grupo PT) y un tercer grupo que desarrolló ECN siguiendo los criterios de Bell. Se les realizó una evaluación clínica completa y se recogieron muestras de meconio en las primeras 48 h de vida realizando también una extracción sanguínea para estudio de diversos marcadores bioquímicos como citoquinas. En el grupo ECN se recogieron muestras una vez iniciada la clínica. En otro subgrupo de niños PT y a T se recogieron muestras de leche materna en el día 0 y día 15 para estudio de miRNAs. Resultados: En el grupo PT, al compararlos con los T se observaron valores más elevados de calprotectina, MPO y PMN-E en heces y menores en la actividad de la fosfatasa alcalina. Y al comparar grupo PT con los niños del grupo ECN, se observaron valores más elevados en este último grupo en los siguientes parámetros: calprotectina, PMN-E, TNF-α, IL-17, MIP, IL-1 β, IL-A y E-selectina, y de forma similar, a excepción de la fosfatasa alcalina también al compararlos con el grupo T. En sangre, se detectaron valores más elevados de IL-1 β, HGF, IL-8 y fosfatasa alcalina en el grupo PT con respecto al grupo T, y el TNF-α y la fosfatasa alcalina fueron significativamente más elevados en pacientes con ECN al compararlos con el grupo PT, y notable aumento en la concentración de IL-1β, IL-8, TNF-α, IL-6, fosfatasa alcalina y NGF cuando comparamos con los T. En la leche materna de niños PT y T se determinaron 379 miRNAs que no se modifican en abundancia en función de la edad gestacional ni de la madurez de la leche participando fundamentalmente en la regulación del desarrollo del sistema inmunológico. La función de los 5 miRNAs más abundantes y más aumentados en la leche inmadura parece estar relacionada con el desarrollo del tubo intestinal, del endotelio y de la función neurológica. Conclusiones: Los neonatos con ECN muestran elevación de parámetros proinflamatorios en heces confirmando la existencia de inflamación en el intestino y la validez de este tipo de muestras para el estudio de diversos biomarcadores. Parece que TNF-α, MIP e IL-1β son parámetros de posible utilidad para detectar la ECN temprana, mientras que IL-17, IL-1α y E-selectina son los marcadores más específicos. En sangre, sólo los niveles circulantes de TNF-α y la actividad de la fosfatasa alcalina parece que podrían ser útiles en la caracterización en la ECN, aunque serían necesarios más estudios para definir un perfil diagnóstico, así como conocer la fisiopatología de la barrera intestinal y su estado en la prematuridad y condiciones de enfermedad.Introduction: The inflammation that occurs during childbirth, greater in prematurity, can persist after birth. This, together with other factors such as the immaturity of the intestinal barrier immune system, can make these newborns susceptible to various diseases such as necrotizing enterocolitis (NEC), with very high morbidity and mortality. The objective of this project is to deepen the knowledge of the relationship between the function of the intestinal barrier and NEC through the study of intestinal and systemic inflammatory markers, also making an approximation to the knowledge of the metabolic pathways involved in the development and intestinal regulation of the newborn through the study of miRNAs in breast milk samples from different groups of newborns. Methodology: It is an observational, descriptive, analytical study of cases and controls. Three groups were established: a group of neonates born ≥37 weeks gestational age (GA) with birth weight ≥ 2,500 g (T group), a group of preterm neonates born before 37 weeks GA (PT group) and a third group that developed NEC following the Bell criteria. A complete clinical evaluation was carried out and meconium samples were collected in the first 48 h of life, also performing a blood extraction to study various biochemical markers such as cytokines. In the ECN group, samples were collected once the symptoms began. In another subgroup of PT and T children, breast milk samples were collected on day 0 and day 15 for the study of miRNAs. Results: In the PT group, when compared with the T group, higher values of calprotectin, MPO and PMN-E were observed in faeces and lower values of alkaline phosphatase activity. And when comparing the PT group with the ECN group, higher values were observed in the latter group in the following parameters: calprotectin, PMN-E, TNF-α, IL-17, MIP, IL-1β, IL-A and E-selectin, and similarly, with the exception of alkaline phosphatase also when compared with the T group. In blood, higher values of IL-1β, HGF, IL-8 and alkaline phosphatase were detected in the PT group with respect to the T group, and TNF-α and alkaline phosphatase were significantly higher in patients with NEC when compared with the PT group, and a notable increase in the concentration of IL-1β, IL-8, TNF-α, IL- 6, alkaline phosphatase and NGF when compared with the T. In the breast milk of PT and T children, 379 miRNAs were determined that do not change in abundance depending on the gestational age or the maturity of the milk, participating in the regulation of development of the immune system. The function of the 5 most abundant and increased miRNAs in immature milk seems to be related to the development of the intestinal tract, the endothelium, and neurological function. Conclusions: Neonates with NEC show elevated proinflammatory parameters in faeces, confirming the existence of inflammation in the intestine and the validity of this type of sample for the study of various biomarkers. It seems that TNF-α, MIP, and IL-1β are potentially useful parameters for detecting early NEC, while IL-17, IL-1α, and E-selectin are the most specific markers. In blood, only the circulating levels of TNF-α and the activity of alkaline phosphatase seem to be useful in the characterization of NEC, although more studies would be necessary to define a diagnostic profile, as well as to know the pathophysiology of the intestinal barrier and their status in prematurity and disease conditions

Premature Birth Infants Present Elevated Inflammatory Markers in the Meconium

Introduction: Prematurity, a well-established risk factor for various intestinal diseases in newborns, results in increased morbidity and mortality. However, the intestinal inflammatory status of preterm (PT) infants has been poorly characterized. Here we have broadly described the intestinal and systemic inflammatory status of PT children. Materials and Methods: Meconium and plasma from 39 PT and 32 full term (T) newborns were studied. Fecal calprotectin, polymorphonuclear leukocyte elastase (PMN-E), TNF, IL-17A, IL-8, IP-10, MCP-1, MIP-1, IL-1β, IL-1α, and E-selectin and the enzymatic activities of myeloperoxidase (MPO) and alkaline phosphatase (AP) in meconium were measured. Plasma levels of AP, hepatocyte growth factor, nerve growth factor (NGF), proinflammatory cytokines, leptin, adiponectin, PAI-1, and resistin were also determined. Correlations with gestational age (GA) and birth weight (BW) were studied. Results: Neutrophil derived PMN-E, MPO and calprotectin were increased in the meconium of PT compared to T newborns, while AP was decreased. No significant differences were found in other inflammatory parameters. Considering data from all children, GA and BW showed inverse correlation with neutrophil markers, while AP directly correlated with BW. Plasma levels of IL-1β and NGF were enhanced in PT infants, and were also negatively correlated with BW. PT children additionally showed neutropenia and decreased adiponectin, leptin, haematocrit, and haemoglobin. These parameters (neutrophils, adiponectin, and so forth) were positively correlated with GA and BW, while IL-8, MCP-1, PAI-1, and plasma AP were negatively correlated. PT children showing postnatal morbidity exhibited increased meconium MPO and MIP-1α. Conclusion: PT neonates present a significant elevation of intestinal inflammatory parameters, characterized by the presence of neutrophil markers, associated with mild systemic inflammation.Ministry of Economy and CompetitivityEuropean Commission SAF2017-88457-R AGL2017-85270-R BFU2014-57736-P AGL2014-58883-RJunta de Andalucia CTS235 CTS164University of Granada (Contrato Puente Program-Plan Propio)Ministry of Education [Spain]Instituto de Salud Carlos III European Commissio

Reflexiones acerca de la evaluación en proceso del trabajo práctico de la cátedra Teoría del diseño y la gestión urbana

La asignatura se ubica en el 4to. Nivel de la Carrera de Arquitectura, de cursado obligatorio. En cada ciclo se aborda un tema “integrador” que opera como un eje transversal de análisis de las temáticas urbanas y permite aplicar los contenidos teóricos de la materia. La propuesta de la Cátedra, tiene como fundamento pedagógico el Aprendizaje Significativo, teniendo presente que los alumnos puedan construir significados y atribuir sentido a lo que aprenden, y que a su vez contribuya al propio crecimiento personal. En función de ello, el alumno busca el significado de la tarea e intenta hallar sentido a lo que aprende, y encuentra que está relacionado con lo que ve y le rodea y se esfuerza por comprender. En este contexto el estudiante tiene que: comprender los objetivos; ser capaz de planificar lo que va a realizar; entender los criterios de evaluación; identificar y superar sus errores. Esto se posibilita mediante la regulación continua, que se efectiviza a través de los procesos de comunicación entre el profesor y los alumnos, y los alumnos entre ellos. Finalmente se demuestra la planificación de los Trabajos Prácticos teniendo en cuenta que la construcción del conocimiento requiere de la ayuda pedagógica del docente, y que el alumno logra conocimientos en función de las actividades que desarrolla, para lo cual diseña una evaluación en proceso, con el objeto de verificarlo en las diferentes etapas, planteando diversas estrategias de exposición con el objeto de socializar los productos parciales entre todos.Área temática 4: Ciudad, Territorio y Paisaje. Gestión - Eje EnseñanzaFacultad de Arquitectura y Urbanism

Linfoma de partes blandas: una causa poco frecuente de lumbalgia

Non-Hodgkin lymphoma represents 3% of malignant neoplasm diseases in adults. Usually it shows up as a single or widespreaded lymphadenopathy. Only 20% show up in an extranodal way with a symptomatology that depends on its placement. We showcase the clinical case of a patient who had lumbosciatica and rapidly progressive right hydronephrosis as an atipical presentation of the disease, due to a soft tissue mass located in L5-S1. After the biopsy she was diagnosed with diffuse large B cell lymphoma.El linfoma no Hodgkin (LNH) corresponde con el 3% de las enfermedades malignas del adulto. Habitualmente aparece como linfadenopatía solitaria o generalizada. Solamente en el 20% de los casos la presentación es extranodal, con sintomatología que depende de la localización. Exponemos el caso de una paciente que tuvo como forma atípica de presentación lumbociatalgia y ureterohidronefrosis derecha rápidamente progresiva por masa de partes blandas a nivel de L5-S1. Tras la biopsia se diagnosticó de Linfoma B difuso de células grandes

Study of the scattering of halo nuclei around the Coulomb barrier

During the past ten years the present collaboration has carried out several experiments related with the study of radioactive nuclei. One of the topics in which we have centered our research, is the scattering of halo nuclei at energies around the Coulomb barrier. As part of this study, we present in this work a review of the results obtained from the scattering of 6He, 11Be and 11Li. The presence of a "halo" in these exotic nuclei is found to have a striking effect on the dynamics of these reactions, making their study an interesting experimental problem and a challenge for existing reaction theories.Ministerio de Ciencia y Tecnología FPA2005-04460, FPA2005-02379, FPA-2000-1592-C03-02, FPA2003-05958, FPA2002- 04181-C04-02/03, FPA2006-13807-c02-0, FPA2009- 07653Programa Español Consolider-Ingenio 2010 CSD2007-0004

Elastic scattering and α -particle production in 6 He + 208 Pb collisions at 22 MeV

Experimental results of the elastic scattering of 6He on 208Pb at E LAB=22 MeV, measured at the CRC facility (Louvain-la-Neuve, Belgium), are presented, including results on the 4He production channel. These data were taken with full angular coverage and high angular resolution. Both experimental cross sections are compared with continuum discretized coupled channels and distorted-wave Born approximation calculations, where direct breakup and transfer to the continuum processes are considered. The elastic data confirm the absence of the Coulomb rainbow, while the distribution of α particles indicates that such production is mostly generated by transfer to the continuum.MICINN FPA2005-04460 FPA200502379 FPA2006-13807-c02-01 FPA2007-63074 FPA2009-07653 FPA2009-07387 FPA2010-22131-C02-01Junta de Andalucía FQM-4964Programa Consolider-Ingenio 2010 CSD2007-00042Comisión Europea HPRI-CT-1999-0011

Activated prothrombin complex concentrate to treat bleeding events in acquired hemophilia A: BAHAS study

[Objective] Activated prothrombin complex concentrate (aPCC) is a bypassing agent indicated to treat bleeds in patients with acquired hemophilia A (AHA). Nevertheless, its efficacy and safety in the real-world setting have not often been addressed.[Methods] We report the experience of Spanish reference centers for coagulation disorders and from acquired hemophilia Spanish Registry (AHASR) from August 2012 to February 2021. Follow-up period of 30 days after aPCC withdrawal.[Results] Thirty patients with a median age of 70 years old, suffering from 51 bleeds treated with aPCC were finally evaluated. As first-line treatment, aPCC stopped bleeding in 13 of 14 (92.9%) cases. aPCC as the second line after recombinant factor VIIa failure, stopped bleeding in all cases. In 17 patients, aPCC was used far from initial bleed control as prophylaxis of rebleeding with 94% effectiveness. No thromboembolic episodes were communicated. One patient developed hypofibrinogenemia, which did not prevent aPCC from halting bleeding. No other serious adverse events possibly or probably associated with aPCC were reported.[Conclusions] This data support aPCC as hemostatic treatment in AHA with high effectiveness and excellent safety profile in acute bleeds and as extended use to prevent rebleedings, even in aging people with high cardiovascular risk.Shire IIR-ES-002899.Peer reviewe

Conocimientos tradicionales relativos a la biodiversidad agrícola

La biodiversidad agrícola, a diferencia de la silvestre, requiere la acción continuada de los agricultores para su conservación, ya que las plantas cultivadas dependen de la intervención humana, con actividades como la selección, la siembra, el abonado, la poda u otras prácticas agrícolas para su supervivencia. Desde la revolución agrícola del Neolítico hasta la actualidad, estas prácticas y conocimientos han ido generando y conservando una gran diversidad, amenazada a partir de la segunda mitad del siglo XX por las causas que se han indicado anteriormente.Peer reviewe

Prognostic implications of comorbidity patterns in critically ill COVID-19 patients: A multicenter, observational study

Background The clinical heterogeneity of COVID-19 suggests the existence of different phenotypes with prognostic implications. We aimed to analyze comorbidity patterns in critically ill COVID-19 patients and assess their impact on in-hospital outcomes, response to treatment and sequelae. Methods Multicenter prospective/retrospective observational study in intensive care units of 55 Spanish hospitals. 5866 PCR-confirmed COVID-19 patients had comorbidities recorded at hospital admission; clinical and biological parameters, in-hospital procedures and complications throughout the stay; and, clinical complications, persistent symptoms and sequelae at 3 and 6 months. Findings Latent class analysis identified 3 phenotypes using training and test subcohorts: low-morbidity (n=3385; 58%), younger and with few comorbidities; high-morbidity (n=2074; 35%), with high comorbid burden; and renal-morbidity (n=407; 7%), with chronic kidney disease (CKD), high comorbidity burden and the worst oxygenation profile. Renal-morbidity and high-morbidity had more in-hospital complications and higher mortality risk than low-morbidity (adjusted HR (95% CI): 1.57 (1.34-1.84) and 1.16 (1.05-1.28), respectively). Corticosteroids, but not tocilizumab, were associated with lower mortality risk (HR (95% CI) 0.76 (0.63-0.93)), especially in renal-morbidity and high-morbidity. Renal-morbidity and high-morbidity showed the worst lung function throughout the follow-up, with renal-morbidity having the highest risk of infectious complications (6%), emergency visits (29%) or hospital readmissions (14%) at 6 months (p<0.01). Interpretation Comorbidity-based phenotypes were identified and associated with different expression of in-hospital complications, mortality, treatment response, and sequelae, with CKD playing a major role. This could help clinicians in day-to-day decision making including the management of post-discharge COVID-19 sequelae. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd