Excess hydrocortisone hampers placental nutrient uptake disrupting cellular metabolism

Low birth weight increases neonatal morbidity and mortality, and surviving infants have increased risk of metabolic and cardiovascular disturbances later in life, as well as other neurological, psychiatric, and immune complications. A gestational excess of glucocorticoids (GCs) is a well-known cause for fetal growth retardation, but the biological basis for this association remains elusive. Placental growth is closely related to fetal growth. The placenta is the main regulator of nutrient transport to the fetus, resulting from the difference between placental nutrient uptake and the placenta’s own metabolism. The aim of this study was to analyze how excess hydrocortisone affects placental glucose and lipid metabolism. Human placenta explants from term physiological pregnancies were cultured for 18 hours under different hydrocortisone concentrations (2.75, 5.5, and 55mM; 1, 2, and 20mg/ml). Placental glucose and lipid uptake and the metabolic partitioning of fatty acids were quantified by isotopic techniques, and expression of specific glucose transporterGLUT1was quantified bywestern blot.Cell viabilitywas assessed byMTT, immunohistochemistry and caspase activity. We found that excess hydrocortisone impairs glucose uptake and lipoprotein lipase (LPL) activity, coincident with a GC-dose dependent inhibition of fatty acid oxidation and esterification. None of the experimental conditions showed an increased cell death. In conclusion, our results show that GC overexposure exerts a dysfunctional effect on lipid transport and metabolism and glucose uptake in human placental explants. These findings could well be directly related to a reduced placental growth and possibly to a reduced supply of nutrients to the fetus and the consequent fetal growth retardation and metabolic programming

Sensitization to isothiazolinones in the Spanish Contact Dermatitis Registry (REIDAC): 2019–2021 epidemiological situation

Background: Current frequency and risk factors for sensitization to methylisothiazolinone (MI), methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), benzisothiazolinone (BIT) and octylisothiazolinone (OIT) in Spain are not well known. Objectives: To study the frequency of sensitization, risk factors and simultaneous sensitization between the four isothiazolinones. Materials and Methods: We analysed all 2019-2021 consecutive patients patch-tested with MI (0.2% aq.), MCI/MI (0.02% aq.), BIT (0.1% pet.) and OIT (0.1% pet) within the Spanish Contact Dermatitis Registry (REIDAC). Results: A total of 2511 patients were analysed. Frequencies of sensitization were: any isothiazolinone 15.7%, MI 6.8%, MCI/MI 4.8%, BIT 3.5% and OIT 0.5%. MI and MCI/MI sensitization was associated with being occupationally active, hand dermatitis, detergents and age over 40. BIT sensitization was associated with leg dermatitis and age over 40. About one in nine MI-positive patients were positive to BIT, whereas one in five BIT-positive patients were positive to MI. Conclusions: Sensitization to MI, MCI/MI and BIT is still common in Spain, while sensitization to OIT is rare. Currently, sensitization to MI and MCI/MI seems to be occupationally related. Although its origin is unknown, sensitization to BIT is more frequent in patients aged over 40 years. Simultaneous sensitization between MI and BIT is uncommon.The Spanish Registry of Contact Dermatitis (REIDAC) is promoted by the Fundación Piel Sana (Academia Española de Dermatología y Venereología), which has received financial support from the Spanish Medicines and Health Products Agency (Agencia Española de Medicamentos y Productos Sanitarios. https://www.boe.es/boe/dias/2022/04/11/pdfs/BOE-A-2022-5975.pdf) and Sanofi. The funders were not involved in the design and conduct of the study, collection, management, analysis and interpretation of data, preparation, review, approval of the manuscript, or decision to submit the manuscript for publication

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

La atención lingüística al alumnado extranjero en el sistema educativo español: normativa, actuaciones y medidas

This article carries out a thorough revision of the linguistic attention to foreign students provided within the Spanish education system. In this paper, it is presented a thorough revision of the linguistic attention to foreign students.The obtained information is structured into several sections: development of the normative upon which the different Autonomous Administrations base build their educational performances interventions and measures; as well as a description of the main measures which are being applied currently been taken in this moment. Finally, it is offered a brief description, plus and a listing of the resources that teachers may can use to be used by teachers, is also provided for teaching Spanish as L2.En este artículo se ha realizado una revisión exhaustiva de la atención lingüística que el sistema educativo español proporciona al alumnado extranjero. La información obtenida se estructura en varios apartados: desarrollo normativo específico sobre el que cada Administración sustenta sus actuaciones y medidas educativas,descripción de las principales medidas que en este momento se están llevando a cabo,y finalmente se ofrece una breve descripción y relación de algunos de los recursos que el profesorado puede utilizar para la enseñanza del español como L2

Entorno : recursos para el conocimiento de Chiclana y la Bahía de Cádiz

Se presenta la memoria de un proyecto educativo que persigue el conocimiento del medio más cercano al alumnado de Educación Primaria y al profesorado del Colegio de Educación Infantil y Primaria Maestra Carmen Seudofeito en Chiclana de la Frontera, Cádiz. Se pretende desarrollar en el profesorado y alumnado un conocimiento directo y activo del entorno de Chiclana y la Bahía de Cádiz, con recursos que les permitan interpretar este entorno y generalizar lo aprendido a entornos más amplios. Los objetivos principales son: 1. Recopilar, restaurar, elaborar, mantener y editar recursos didácticos sobre el entorno de Chiclana y la Bahía de Cádiz, y en menor medida, de Andalucía. Estos recursos tiene cinco tipos de formato: un jardín botánico escolar, una maqueta en relieve 1:10000 del término de Chiclana, colecciones de diapositivas de elaboración propia, láminas murales, láminas personales. 2. Usar estos recursos con el alumnado, tanto en el centro como en visita de estudios. Valorar su utilidad y hacer las correcciones que correspondan. 3. Incorporar la informática en la elaboración, edición y exposición de estos recursos. El proceso consta de varias fases: se realizan cuidados sobre labores agrícolas para crear y mantener un jardín botánico; se actualiza la maqueta del relieve del término municipal de Chiclana y se completa el manto de arbolado de muchas de sus áreas; se realizan láminas murales con diseño propio sobre el barrio de La Banda, sobre el término municipal y sobre la Bahía de Cádiz; elaboración y actualización de láminas plastificadas cuyos temas fueron: el patio y sus plantas y animales, el patio y los ecosistemas del jardín botánico escolar, el barrio de La Banda, la ciudad de Chiclana, el acantilado, las dunas y la playa de la Barrosa, la Bahía de Cádiz; láminas dibujadas cuyos temas fueron: las lagunas chiclaneras, aves y plantas, los huertos, las salinas, la bahía, el acantilado, plantas del pinar de la Barrosa, planos del jardín botánico de San Fernando, planos de los parques urbanos de La Soledad y de la Huerta del Rosario, rutas al parque de Grazalema, rutas al parque de los Alcornocales; por último se realizan salidas a la naturaleza en autobús de un día hasta cuarto curso y de un día o más para el alumnado de quinto o sexto curso. Los resultados obtenidos fueron de aceptación en docentes del centro y del colegio vecino, pero no consiguió atraer a todo el profesorado al que estaba dirigido, este hecho nos hizo repensar el proyecto hacia la elaboración, no tanto de guías, sino de nuevos recursos para quien estuviera realmente interesado. Los materiales utilizados fueron: maderas, materiales para tareas agrícolas, transparencias, plastificados, pinturas, software informático, diapositivas, discos, disquetes, láminas y mapas de relieve.Junta de Andalucía. Consejería de Educación y CienciaAndalucíaES

Revista de educación

Resumen tomado de la publicación. Número monográfico con el título: La enseñanza aprendizaje del español como segunda lengua (L2) en contextos educativos multilingüesSe realiza una revisión exhaustiva de la atención lingüística que el sistema educativo español proporciona al alumnado extranjero. La información obtenida se estructura en los siguientes apartados: desarrollo normativo específico de cada Administración en torno a sus actuaciones e iniciativas educativas, descripción de las principales medidas que en este momento se están llevando a cabo, y finalmente una breve descripción y relación de algunos recursos que el profesorado puede utilizar para la enseñanza del español como L2 (segunda lengua).MadridBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín, 5 - 3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]

Zahínos, 'La ruta del cuento'

El trabajo obtuvo un Premio Tomás García Verdejo a las buenas prácticas educativas en la Comunidad Autónoma de Extremadura para el curso 2021/2022. Modalidad APartiendo de la actividad de la biblioteca del CEIP Luis Chamizo de Zahínos (Badajoz) se presenta un proyecto con el que se pretende trabajar distintos aspectos: la literatura infantil, a través de la interiorización de los cuentos; la expresión oral, interpretándolos y dramatizándolos; las tecnologías de la información y la comunicación, grabando los cuentos, colgándolos en Internet y disponiendo de una ruta literaria a través de códigos QR que los visitantes de la localidad podrán escanear para disfrutarlos y ofrecer una alternativa de ocio en el entorno del centro. A través de la ruta literaria creada se ofrece una forma de turismo rural, actividad física, uso responsable de las tecnologías y difusión de la actividad del centro al resto de la comunidad educativaES