Control of early cell death by BDNF in the chick retina

8 páginas, 6 figuras, 1 tabla.The developing chick retina undergoes at least two discrete periods of programmed cell death. The earlier period coincides with the main onset of neuron birth and migration (embryonic day 5-7), whereas the latter one corresponds to the well-documented process of retinal ganglion cell death following tectal innervation (embryonic day 10-14; Rager, G. H. (1980) Adv. Anat. Embryol. Cell Biol. 63, 1-92). In the early period, apoptosis is induced by nerve growth factor (NGF) acting via its p75 receptor (Frade, J. M., Rodríguez-Tébar, A. and Barde, Y.-A. (1996) Nature 383, 166-168). Here, we show that the application of brain-derived neurotrophic factor (BDNF) to chick embryos in ovo prevented retinal cell death in the early period, whereas exogenously applied NGF and neurotrophin-3 had no such effect. The addition of BDNF to embryos resulted in about 70% increase in the number of retinal ganglion cells in both E6 and E9 retinas relative to controls. BDNF is first expressed in both the pigment epithelium and neural retina of embryonic day 4 embryos, and at the same stage of development, its TrkB receptor is expressed in the neural retina. Our data indicate that early cell death is an important process in the neurogenesis of retinal ganglion cells and is regulated by locally produced BDNF.This research was financed by grants from the DGCYT (Ministery of Science of Spain, no. PB95-0025 and PB94-0102-B), Regional Governments of Madrid and Canary Islands, Spain, and European Union, Programme Biotech (no. 960024).Peer reviewe

Reflexiones derivadas de la pandemia COVID-19

While we were drafting the recommendations for the joint contingency plan between the Spanish Society of Intensive Care and Coronary Unit Nursing (SEEIUC) and the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC), predictions were overtaken by events with regard to the magnitude of the COVID-19 pandemic. Members informed us of the lack of personal protection equipment (PPE), the rapid provision of improvised ICUs in various hospital areas and the recruitment of nurses to cover shifts. The failure to recognise the specialty of critical care nursing, included in the macro-specialty of medical-surgical nursing and not yet developed, has highlighted the urgent need to learn from our mistakes: specialisation, increase the number of nurses in teams and protect the public health syste

The Unfolded Protein Response and the Phosphorylations of Activating Transcription Factor 2 in the trans-Activation of il23a Promoter Produced by β-Glucans

Producción CientíficaCurrent views on the control of IL-23 production focus on theregulation ofil23a, the gene encoding IL-23 p19, by NF- Bincombination with other transcription factors. C/EBP homolo-gous protein (CHOP), X2-Box-binding protein 1 (XBP1), acti-vator protein 1 (AP1), SMAD, CCAAT/enhancer-binding pro-tein (C/EBP ), and cAMP-response element-binding protein(CREB) have been involved in response to LPS, but no data areavailable regarding the mechanism triggered by the fungalmimic and -glucan-containing stimulus zymosan, which pro-duces IL-23 and to a low extent the related cytokine IL-12 p70.Zymosan induced the mobilization of CHOP from the nuclearfractions to phagocytic vesicles. Hypha-formingCandidaalsoinduced the nuclear disappearance of CHOP. Assay of tran-scription factor binding to theil23apromoter showed anincrease of Thr(P)-71–Thr(P)-69-activating transcription fac-tor 2 (ATF2) binding in response to zymosan. PKC and PKA/mitogen- and stress-activated kinase inhibitors down-regulatedThr(P)-71–ATF2 binding to theil23apromoter andil23amRNA expression. Consistent with the current concept ofcomplementary phosphorylations on N-terminal Thr-71 andThr-69 of ATF2 by ERK and p38 MAPK, MEK, and p38 MAPKinhibitors blunted Thr(P)-69–ATF2 binding. Knockdown ofatf2mRNA with siRNA correlated with inhibition ofil23amRNA, but it did not affect the expression ofil12/23bandil10mRNA. These data indicate the following: (i) zymosan decreasesnuclear proapoptotic CHOP, most likely by promoting its accu-mulation in phagocytic vesicles; (ii) zymosan-inducedil23amRNA expression is best explained through coordinated B-and ATF2-dependent transcription; and (iii)il23aexpressionrelies on complementary phosphorylation of ATF2 on Thr-69and Thr-71 dependent on PKC and MAPK activities

Un nuevo Museo Arqueológico Nacional. Una rehabilitación compleja

Rehabilitar un edificio emblemático con éxito resulta una labor extremadamente compleja, no solo por las dificultades técnicas y normativas a la hora de conservar lo existente sin que pierda su personalidad, sino también porque se convierte en foco de todas las miradas

Seven microaneurysms: Description of an experimental rodent model for neurovascular training

AIM: To demonstrate the microsurgical procedures, and to evaluate the feasibility of living models of experimental neurovascular training by developing new complex vascular exercises mimicking the most common intracranial aneurysms. MATERIAL and METHODS: The procedures were performed under a Zeiss (OPMI pico f170) microscope using basic microsurgery instruments, 10/0 Nylon and blue Polypropylene micro-sutures. We selected adult albino Wistar rats weighing between 258 and 471g each. Seven different aneurysm types were created using carotid, jugular, cava, aorta and femoral vessels. RESULTS: Seven types of aneurysm were designed and created in the rat with a high-medium successful rate. There are differences in terms of realism and the difficulty of performance, according to the different types: lateral wall, bifurcation, top of the basilar, fusiform, fusiform + involved branch, Anterior Communicating Artery (ACoA) and giant. The steps and technical issues to produce these exercises are described. CONCLUSION: We show the feasibility of creating several types of aneurysm using different vessels in a rodent model. Training on these models help to improve microsurgical skills, allowing safe practice for neurosurgeons in all stages of their caree

Innovación en procedimientos de evaluación de resultados de aprendizaje con soporte tecnológico y atención a criterios de inclusión (E-RA-INCLUYE)

Memoria ID2022-232 Ayudas de la Universidad de Salamanca para la innovación docente, curso 2022-2023

Preoperative psychological profile of women with increased risk of breast cancer

Aim: analyze depressive and anxiety symptomatology, body image and quality of life in a group of women with genetic vulnerability to breast cancer who were going to undergo a riskreducing mastectomy. Method:184 women participated in this study, all of whom had an increased risk of breast cancer, either because they were BRCA1/2 mutation carriers or because they had several affected relatives. The psychological instruments used were: Hospital Anxiety and Depression Scale, Body Image Scale, European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 and BR23. Results: The results of this study showed that the participants presented clinical anxiety symptomatology and subclinical depressive symptomatology. However, all the sample were at normative levels in body image and quality of life. Participants with previous diagnosis of cancer showed, higher dissatisfaction with their body image, lower levels on the scales of physical, and cognitive and global functioning on quality of life, as well as higher fatigue, more general pain also in the breast and in the arm compared to women without diagnosis. Conclusions: BRCA1/2 non-mutation carriers showed more symptomatology in the breast and in the arm fatigue than BRCA1/2 mutation carriers. BRCA1/2 mutation carriers had more economic difficulties than non-carriers. It is highly recommended a psychological intervention before a risk-reducing surgery.Objetivo: analizar los niveles de sintomatología ansiosa y depresiva, imagen corporal y calidad de vida en un grupo de mujeres con vulnerabilidad genética de cáncer de mama que se iban a someter a una mastectomía reductora de riesgo. Método: 184 mujeres participaron en este estudio, todas ellas tenían riesgo aumentado de cáncer de mama, bien por ser portadoras de una mutación BRCA1/2 o por agregación familiar. Los instrumentos utilizados fueron: Escala de Ansiedad y Depresión Hospitalaria, Escala de Imagen Corporal, European Organisation for Research and Treatment of Cancer calidad de vida oncológica C30 y BR23. Resultados: Los resultados de este estudio mostraron que las participantes presentaban niveles clínicos en sintomatología ansiosa y subclínicos en sintomatología depresiva. Sin embargo, se encontraban en niveles normativos en imagen corporal y calidad de vida. Las participantes con antecedentes oncológicos manifestaban, mayor insatisfacción con la imagen corporal, niveles inferiores en las escalas de funcionamiento físico, cognitivo y global de la calidad de vida, así como mayor fatiga, dolor general, en el brazo y en la mama en comparación con las mujeres sin diagnósticos previos. Conclusiones: Las mujeres sin mutación poseían mayor sintomatología en la mama y en el brazo que las mujeres con mutación, las cuales presentaban más dificultades económicas que las mujeres no portadoras. Evidenciando la necesidad de realizar una intervención psicológica antes de la cirugía especialmente en este colectivo

Unraveling the effect of silent, intronic and missense mutations on VWF splicing : contribution of next generation sequencing in the study of mRNA

Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to the identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. RNA extracted from patient platelets and leukocytes was amplified by RT-PCR and sequenced using Sanger and next generation sequencing techniques. Eight mutations affected VWF splicing: c.1533+1G>A, c.5664+2T>C and c.546G>A (p.=) prompted exon skipping; c.3223-7_3236dup and c.7082-2A>G resulted in activation of cryptic sites; c.3379+1G>A and c.7437G>A) demonstrated both molecular pathogenic mechanisms simultaneously; and the p.Cys370Tyr missense mutation generated two aberrant transcripts. Of note, the complete effect of three mutations was provided by next generation sequencing alone because of low expression of the aberrant transcripts. In the remaining 10 mutations, no effect was elucidated in the experiments. However, the differential findings obtained in platelets and leukocytes provided substantial evidence that four of these would have an effect on VWF levels. In this first report using next generation sequencing technology to unravel the effects of VWF mutations on splicing, the technique yielded valuable information. Our data bring to light the importance of studying the effect of synonymous and missense mutations on VWF splicing to improve the current knowledge of the molecular mechanisms behind von Willebrand disease. identifier:02869074

Plan de contingencia para los servicios de medicina intensiva frente a la pandemia COVID-19

In January 2020, the Chinese authorities identified a new virus of the Coronaviridae family as the cause of several cases of pneumonia of unknown aetiology. The outbreak was initially confined to Wuhan City, but then spread outside Chinese borders. On 31 January 2020, the first case was declared in Spain. On 11 March 2020, The World Health Organization (WHO) declared the coronavirus outbreak a pandemic. On 16 March 2020, there were 139 countries affected. In this situation, the Scientific Societies SEMICYUC and SEEIUC, have decided to draw up this Contingency Plan to guide the response of the Intensive Care Services. The objectives of this plan are to estimate the magnitude of the problem and identify the necessary human and material resources. This is to provide the Spanish Intensive Medicine Services with a tool to programme optimal response strategies