Aplicació de la microdiàlisi cerebral a l'estudi de la resposta metabòlica i inflamatòria en el traumatisme cranioencefàlic moderat i greu

Consultable des del TDXTítol obtingut de la portada digitalitzadaEls traumatismes cranioencefàlics (TCE) són la primera causa de mort i discapacitat en la població menor de 40 anys de qualsevol païs industrialitzat. Les xifres de mortalitat són encara elevades, oscil·lant, en la majoria de centres, entre el 30-40%. Els mals resultats neurològics supera en molts casos el 55%. Aquests resultats comporten importants repercusions sanitàries, econòmiques i socials, i expliquen el progressiu interés en la investigació traslacional de les lesions neurotraumàtiques. Malgrat el millor coneixement de la fisiopatologia del TCE i de l'avenç en les tècniques de neuromonitoratge i en el tractament, el pronòstic d'aquests pacients ha assolit una meseta. És conegut que tot i que una part considerable de les lesions es produeixen de forma immediata a l'impacte (lesions primàries), moltes d'elles apareixen en un periode variable de temps després del traumatisme (lesions secondàries). La hipòxia tissular d'origen isquèmic o no isquèmic constitueix la lesió secondària de major prevalència als TCE. A més, genera o potencia l'aparició de processos metabòlics anòmals i pot induïr una resposta inflamatòria a nivell tissular. Tanmateix, les dades obtingudes d'estudis en models experimentals i clínics han demostrat de forma inequívoca que la resposta inflamatòria cerebral juga un paper predominant en la lesió secondària postraumàtica, facilitant l'alteració de la permeabilitat de la barrera hematoencefàlica (BHE), l'edema cerebral i secondàriament la tumefacció cerebral i l'augment de la pressió intracranial. En els darrers anys, la introducció de noves tecnologies en l'àmbit clínic ha permès utilitzar tècniques revolucionàries de neuromonitoratge a la capçalera del pacient. Una d'elles ha estat la microdiàlisi cerebral, que permet el monitoratge neuroquímic quasi on-line dels nivells extracel·lulars de certs metabolits. El principi bàsic d'aquesta tècnica és la introducció al parènquima cerebral d'un catèter que conté una membrana semipermeable al seu extrem distal. La membrana de diàlisi permet la difusió lliure d'aigua i soluts entre l'espai extracel·lular cerebral i una solució salina perfosa mitjançant una microbomba. La possibilitat d'obtenir informació del metabolisme cerebral a la capçalera del pacient ens permet estudiar la resposta metabòlica a determinats procediments terapèutics, així com preveure l'establiment del dany tissular degut a la hipòxia tissular cerebral. A més, la recent aparició al mercat de noves membranes de microdiàlisi, amb porus de filtratge majors, ha obert la possibilitat d'estudiar proteïnes de major tamany, implicades en els processos neuroinflamatoris desencadenats després d'un TCE, com l'estudi del paper de les metal·loproteïnases de matriu (MMPs) a la lesió cerebral traumàtica. La present tesi pretèn aportar noves aplicacions de la microdiàlisi cerebral en l'estudi del metabolisme i de la neuroinflamació del pacient neurotraumàtic. En primer lloc l'aplicació de la microdiàlisi com a eina diagnòstica en la detecció de la hipòxia cerebral isquèmica, ens permet validar per una banda la superioritat d'aquesta tècnica respecte una altra de més convencional, com és el cas del càlcul de les diferencies arterio-jugulars de lactat i l'índex lactat-oxigen. A més, la utilització combinada de la microdiàlisi amb la pressió tisular d'oxigen ens permet determinar l'efecte de la hiperòxia normobàrica en el metabolisme cerebral d'aquests pacients. En segon lloc, la tesi aprofundeix en l'estudi d'unes proteases que es sobreexpressen com a conseqüència dels processos inflamatoris desencadenats a la fase aguda del TCE, les MMPs, que es relacionen amb l'alteració de la BHE. La possibilitat de poder recuperar proteïnes amb un pes mol·lecular superior al dels catèters de primera generació, obre pas a múltiples opcions terapèutiques. Una d'elles seria dissenyar estratègies farmacològiques per bloquejar o modular la sobreexpressió d'aquestes proteases a la fase aguda del TCE, amb la finalitat de limitar l'alteració de la BHE i el dany tissular postraumàtic cerebral.Traumatic brain injury (TBI) is the leading cause of death and disability worldwide among the population under the age of 40 years. Mortality is still high, and it fluctuates between 30% and 40% in the majority of centers. The poor neurologic outcome exceeds in many cases the 55%. These results lead to important sanitary, economic and social consequences, and explain the progressive interest in the translational research of brain traumatic lesions. In spite of the better understanding of TBI pathophysiology and the progress achieved in neuromonitoring techniques and treatment, the prognosis of these patients has reached a plateau. It is well known that even though a considerable part of injury is produced immediately after impact (primary brain injury), a great part appear in a variable period of time after traumatism (secondary brain injury). Tissular hypoxia, with ischemic or not ischemic origin, is the most prevalent secondary brain injury in TBI patients. Moreover, it generates or boost metabolic alterated processes and can induce an inflammatory tissular response. Data obtained from experimental and clinical models have firmly shown that inflammatory response has a crucial role in the posttraumatic secondary injury, promoting blood-brain barrier (BBB) increased permeability, brain edema and secondly brain tumefaction and increases in intracranial pressure. New clinical technologies have recently permitted to use revolutionary neuromonitoring techniques at the patient bedside. One of them is brain microdialysis, that allows brain neurochemistry monitoring of several metabolites in the extracellular space. The basic principle about this technique is the implantation of one catheter in the brain parenchyma, that contains a semipermeable membrane in the distal part. The dialysis membrane allows free difusion of water and molecules between the extracellular space and a saline solution, which is perfused by using a micropump. Due to the fact that we are able to obtain brain metabolic information at the patient bedside, we can study the metabolic response to some therapeutic procedures, as well as prevent tissular injury due to brain hypoxia. Moreover, the new generation membranes, with larger filtration membrane pores, has opened the possibility to study proteins with higher molecular weight implicated in the neuroinflammatory processes triggered after a TBI, such as the matrix metaloproteinases (MMPs). The present thesis aims to provide new applications of brain microdialysis in the metabolic and neuroinflammation field from the brain trauma patient. First, the microdialysis application as a diagnosis tool to detect brain ischemic hypoxia enables to validate the superiority of this technique in front of another one more conventional, like the arteriojugular venous differences of lactate and lactate-oxygen index. Moreover, the combinated use of brain tissue oxygen pressure and brain microdialysis allows us to analyse the normobaric hyperoxia effects on the brain metabolism of these patients. Second, the thesis explores the role of certain proteases that are overexpressed after a TBI, named MMPs, which are related to BBB disruption. The possibility to recover proteins with higher molecular weight opens multiple therapeutic options. One of them would be to design a pharmacological blockade or modulation of these proteases in the acute phase from TBI, with the goal to reduce BBB permeability and brain tissular damage

La relevancia de los recursos cognitivos en un entrenamiento de natación sincronizada : El caso de andamiajes y affordances

En el entrenamiento de natación sincronizada confluyen elementos artísticos y deportivos de alta competitividad. Nos preguntamos cómo contribuyen los andamiajes y affordances a la estabilización de los recursos cog-nitivos de la entrenadora y de las nadadoras del equipo olímpico español de natación sincronizada. Vamos a detenernos en qué se entiende por recursos cognitivos y en los posibles sentidos de andamiaje y affordance. Y examinamos las pautas comunicativas y el proceso de trabajo que da lugar al entrenamiento de natación sincronizada. Proponemos una etnografía cognitiva de los entrenamientos, un método innovador que sistematiza los patrones de actividad de las interacciones locales entre los participantes de la formación deportiva. Hemos utilizado el programa ELAN e incorporado las técnicas de descripción jeffersonianas que provienen del método de análisis conversacional. Los resultados muestran cómo el proceso de entrenamiento implica la interacción en un entorno que incluye otros agentes sociales, recursos materiales y modelos conceptuales que se retroalimentan.In synchronized swimming, highly competitive trainings arts and sports elements converge. We wonder how scaffoldings and affordances contribute to the stabilization of cognitive resources among the trainer and swimmers of the Spanish Olympic synchronized swimming team. We dwell on what is taken as cognitive resources and the role of scaffolding and affordances. We analyze communication patterns and examine the work process leading to synchronized swimming. We propose a cognitive ethnography on training, an innovative method that explains the patterns of activity of local interactions among participants in sports. We applied ELAN program and incorporated Jeffersonian transcriptions that come from conversational analysis method. Results show how the training process involves interaction in an environment that includes social agents, material resources and conceptual models that feed each other

Advance directives and real-world end-of-life clinical practice : a case-control study

Background Advance directives (ADs) have been legally regulated to promote autonomy over health decisions among patients who later lose decision-making capacity. Aims and objectives To analyse the differences in clinical practice at end of life among people who had completed an AD versus those who had not. Methods Retrospective case-control study (1:2), matched by age, sex, year, cause of death and region of residence. The data sources used were the ADs registry, central registry of insured persons, hospital discharge, pharmacy and billing databases, and the mortality registry. Conditional logistic regression models (crude and adjusted by socioeconomic level) were performed. The outcome variable was the frequency of medical procedures performed during the last year of life. Results 1723 people with ADs who died in Catalonia during 2014-2015 were matched with 3446 dead controls (without ADs). Thoracentesis was the procedure with the greatest reduction among women with an AD (adjusted OR (OR adj) 0.54, 95% CI: 0.32 to 0.89) in conjunction with artificial nutrition (OR adj 0.54, 95% CI: 0.31 to 0.95). Intubation was the procedure with the greatest reduction (OR adj 0.56, 95% CI: 0.33 to 0.94) among men. Slight differences could be seen in the case of cancer deaths. There were no relevant differences when adjusting by socioeconomic level. Conclusions ADs are an effective tool to adjust the realisation of some procedures at end of life. These results can help better plan for the treatment of patients with ADs, as well as increase the awareness among clinical personnel, families and the general population

Long‐term effectiveness of a nurse‐led smoking cessation clinic at a comprehensive cancer center

Purpose: Smoking cessation interventions should be promoted in cancer centers to improve clinical outcomes among cancer patients and the quality of life of cancer-free patients and survivors. The aim of the present study was to examine long-term abstinence (1, 3, and 5 years) among smokers who received an intensive nurse-led smoking cessation intervention.Design: A prospective follow-up study was conducted in a smoking cessation clinic in Barcelona.Methods: The study included 479 smokers who received a nurse-led smoking cessation intervention that included motivational interviewing, psychological support, behavioral change counseling, promotion of smoke-free policies, and relapse-prevention strategies, as well as pharmacotherapy if necessary, for 12 months. We calculated overall and sex-specific 1-, 3-, and 5-year abstinence probabilities (Kaplan-Meier curves) and adjusted hazard ratios (aHRs) of relapse with 95% confidence intervals (CIs) using Cox regression.Findings: The overall probability of abstinence at 1 and 5 years was 0.561 (95% CI: 0.516-0.606) and 0.364 (95% CI: 0.311-0.417), respectively. Females had a higher, but not significant, hazard ratio for relapse compared to males (aHR = 1.180; 95% CI: 0.905-1.538). Attending <5 visits was the most remarkable determinant of relapsing compared to attending 5-9 visits or =10 visits, both overall and by sex (p for trend: overall, p < 0.001; males, p = 0.007; and females, p < 0.001).Conclusions: Abstinence probability decreased over the 5-year follow-up but was relatively high. Males had higher abstinence rates than females in all follow-up periods. Completeness of the intensive intervention was the main predictor of cessation.Clinical Relevance: Smoking cessation interventions should consider sex and incorporate strategies to increase adherence to obtain higher long-term abstinence rates

Do cross-food allergies to propofol exist?

Alergia a la comida; Sensibilización alimentaria; PropofolFood allergy; Food sensitization; PropofolAl·lèrgia alimentària; Sensibilització alimentària; PropofolBackground: Propofol is a short and rapidly acting intravenous anesthetic extensively used for the induction and maintenance of general anesthesia. It is a lipid emulsion that contains soybean oil, purified egg phosphatide, and egg lecithin. Therefore, the package leaflet indicates that its administration is contraindicated in patients allergic to soy, eggs, or peanuts. Our study aimed to determine whether patients with proven food allergies are allergic to propofol. Methods: Patients of all ages allergic to soy, eggs, or peanuts who agreed to undergo skin testing for propofol allergies were included. The subjects first underwent a skin test to confirm food allergies. If candidates were negative, they were excluded. If the result was positive, a propofol skin test was performed. Results: Sixty-four patients with confirmed food allergies underwent a propofol skin test. Only one was positive in the propofol skin test (1.6%). The patient was allergic to peanuts and soybeans. These results reinforce the idea that there is no justification for avoiding propofol use in these subjects. Conclusions: Propofol can be safely administered to patients allergic to soy, eggs, or peanuts. We recommend caution in patients with a history of anaphylaxis after ingestion of the above-mentioned foods

Dinámica, Factores condicionantes y posibles causas de la formación de la tartera de Cambrils (Solsonès, Lleida)

Landslides and rockfalls are a common hazard in mountain areas like the Pyrenees. However, due to the difficulty of access and therefore of data acquisition, and the low density of population they are poorly studied. The Tartera de Cambrils, is located in a small town in the Solsonès region, Catalonia, and is the product of ancient landslides and succeeding rockfalls. These processes can endanger different infrastructures in the village of Cambrils such as the road, the sports centre, the salt flats called 'El Salí' (currently also being used for tourist activity), two inns and several houses. This study aims to determine the processes that caused the initial landslides, those that occur at the rock slope nowadays and their causative factors. For this, we compiled information from the literature, conducted a field study building a geologic and geomorphologic cartography and acquired LiDAR data, with a Terrestrial Laser Scan, and photographs in order to produce three-dimensional point clouds. We also analyse the rock-cliff stability using photogrammetry and LiDAR data and direct measures of rock mass discontinuities. The bedding dips smoothly and contrary to the slope, making planar sliding an unprovable mechanism, favouring wedge sliding and toppling. The rock discontinuities are the main causative factor of rockfalls. Rockfall originates from rock fronts of decametric volume along the main scarp and on the scree. These rock fronts rotated respect to the rock in situ. The farther away from the main scarp, the larger the rotation of the blocks. The analysis of the fractures allows estimating an important possibility of rockfall directly affecting the inns and the road and provides fundamental data for the development of protection measures

Magnetic domains in SrFe12O19/Co hard/soft bilayers

ESRF (The european Synchrotron) User Meeting 2022, 7 - 9 February, 2022 . -- online meeting . -- https://www.esrf.fr/fr/home/events/conferences/2022/user-meeting-2022.html .-- Youtube access: https://www.youtube.com/playlist?list=PLsWatK2_NAmyYnkC-bXhvT70wsYaTmojqThe nature of the magnetic coupling between a SrFe12O19 particle (hard phase) and a Co layer grown on top (soft phase) has been studied by means of photoemission electron microscopy (PEEM) and spatially-resolved x-ray absorption (XAS) and magnetic circular dichroism (XMCD) at CIRCE, ALBA synchrotron (Spain). Our study reveals the soft metallic overlayer presents an in-plane magnetization despite the strong out-of-plane magnetocrystalline anisotropy of the hard platelet. Thus, the two phases show completely uncorrelated magnetic domain patterns. Micromagnetic simulations seem to indicate the degree of exchange-coupling is low or null, although the conditions for rigid coupling are a priori well met

Circulating tumor DNA reveals complex biological features with clinical relevance in metastatic breast cancer

Cancer; Predictive markersCàncer; Marcadors predictiusCáncer; Marcadores predictivosLiquid biopsy has proven valuable in identifying individual genetic alterations; however, the ability of plasma ctDNA to capture complex tumor phenotypes with clinical value is unknown. To address this question, we have performed 0.5X shallow whole-genome sequencing in plasma from 459 patients with metastatic breast cancer, including 245 patients treated with endocrine therapy and a CDK4/6 inhibitor (ET + CDK4/6i) from 2 independent cohorts. We demonstrate that machine learning multi-gene signatures, obtained from ctDNA, identify complex biological features, including measures of tumor proliferation and estrogen receptor signaling, similar to what is accomplished using direct tumor tissue DNA or RNA profiling. More importantly, 4 DNA-based subtypes, and a ctDNA-based genomic signature tracking retinoblastoma loss-of-heterozygosity, are significantly associated with poor response and survival outcome following ET + CDK4/6i, independently of plasma tumor fraction. Our approach opens opportunities for the discovery of additional multi-feature genomic predictors coming from ctDNA in breast cancer and other cancer-types

Pediatric HIV care cascade in southern mozambique: Missed opportunities for early ART and re-engagement in care

© 2020 Wolters Kluwer Health, Inc. All rights reserved. Background: There are 170,000 children living with HIV in 2017 in Mozambique. Scaling-up HIV care requires effective retention along the cascade. We sought to evaluate the pediatric cascade in HIV care at the Manhiça District Hospital. Methods: A prospective cohort of children <15 years was followed from enrollment in HIV care (January 2013 to December 2015) until December 2016. Loss to follow-up (LTFU) was defined as not attending the HIV hospital visits for ≥90 days following last visit attended. Results: From the 438 children included {median age at enrollment in care of 3,6 [interquartile range (IQR): 1.1-8.6] years}, 335 (76%) were antiretroviral therapy (ART) eligible and among those, 263 (78%) started ART at enrollment in HIV care. A total of 362 children initiated ART during the study period and the incidence rate of LTFU at 12, 24, and 36 months post-ART initiation was 41 [95% confidence interval (CI): 34-50], 34 (95% CI: 29-41), and 31 (95% CI: 27-37) per 100 children-years, respectively. Median time to LTFU was 5.8 (IQR: 1.4-12.7) months. Children 5-9 years of age had a lower risk of LTFU compared with children <1 year [adjusted subhazard ratio 0.36 (95% CI: 0.20-0.61)]. Re-engagement in care (RIC) was observed in 25% of the LTFU children. Conclusions: The high LTFU found in this study highlights the special attention that should be given to younger children during the first 6 months post-ART initiation to prevent LTFU. Once LTFU, only a quarter of those children return to the health unit. Elucidating factors associated with RIC could help to fine tune interventions which promote RIC

Population structure and genetic variability in wild and farmed Mediterranean populations of gilthead seabream and European seabass inferred from a 60K combined species SNP array

13 Pág.Knowledge of population structure and genetic diversity within and between wild and farmed populations of gilthead sea bream (Sparus aurata) and European seabass (Dicentrarchus labrax) is important to achieve sustainable aquaculture production of these species and to assess the risk of genetic impacts of fish escaped from farms. Previous population genetic studies on these species have been based on a limited number of genetic markers and samples. In this study, these features were assessed using samples from 24 seabream and 25 seabass populations distributed throughout the Mediterranean Sea, and 3 wild seabream Atlantic populations. Samples were genotyped with a newly developed combined species SNP array that includes ~60K SNPs. Data from sequencing pools of individual DNA from the same populations were also used. Different approaches were employed for identifying the extent of population stratification within species. The effective population size (a parameter inversely related to the rate at which genetic variability is lost) was estimated for each population based on linkage disequilibrium. Population structure results revealed a clear differentiation between wild and farmed populations in both species. Wild populations showed a low degree of differentiation, particularly in seabream. Despite this, a slight differentiation was observed between Atlantic and Mediterranean seabream populations and between western and eastern Mediterranean seabass populations. However, farmed populations were quite heterogeneous and showed a high degree of differentiation. Some farmed populations of both species showed a genetic makeup similar to that found in wild populations. In general, the effective population size was large (> 1000) for wild and small (< 100) for farmed populations of both species. About 40% of the seabream and 80% of the seabass farmed populations had estimates of effective population size smaller than 50 highlighting the need of applying measures to control the rate at which genetic variability is lost.This work was supported by the European Commission Horizon 2020 (H2020) Framework Programme through grant agreement no 727315 MedAID project (Mediterranean Aquaculture Integrated Development) and by MCIN/ AEI /10.13039/501100011033 (Project PID2020-114426GB-C2).Peer reviewe