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Summary: The blood enzyme glutamate-oxaloacetate transaminase (GOT) has been postulated as an effective therapeutic to protect the brain during stroke. To demonstrate its potential clinical utility, a new human recombinant form of GOT (rGOT) was produced for medical use.We tested the pharmacokinetics and evaluated the protective efficacy of rGOT in rodent and non-human primate models that reflected clinical stroke conditions.We found that continuous intravenous administration of rGOT within the first 8 h after ischemic onset significantly reduced the infarct size in both severe (30%) and mild lesions (48%). Cerebrospinal fluid and proteomics analysis, in combination with positron emission tomography imaging, indicated that rGOT can reach the brain and induce cytoprotective autophagy and induce local protection by alleviating neuronal apoptosis.Our results suggest that rGOT can be safely used immediately in patients suspected of having a stroke. This study requires further validation in clinical stroke populations.

Esta conversación con José Castillo Ruiz cabalga el camino de la configuración del patrimonio agrario como bien cultural, reconociendo el valor del conjunto de bienes vinculados a la actividad agraria. Atraviesa distintas aristas del proceso, desde su inicio hasta la situación actual, haciendo foco en los desafíos para la planificación urbana y las administraciones públicas en distintos contextos. Analiza su significado como elemento para el desarrollo de turismo cultural y los riesgos derivados de ello. El objetivo de esta entrevista es divulgar el nuevo concepto, conocer su estado de consolidación y su valor para el desarrollo de escenarios urbanos más sostenibles y, en ese sentido, los desafíos actuales desde el hacer disciplinar. Castillo Ruiz es una referencia clave en el tema por su trayectoria, destacando su aporte a la construcción teórica y normativa, así como su extenso y comprometido trabajo en la divulgación.

Introduction Given the increasing prevalence of both obesity and pre-diabetes in pregnant adults, there is growing interest in identifying hyperglycaemia in early pregnancy to optimise maternal and perinatal outcomes. Multiple organisations recommend first-trimester diabetes screening for individuals with risk factors; however, the benefits and drawbacks of detecting glucose abnormalities more mild than overt diabetes in early gestation and the best screening method to detect such abnormalities remain unclear.Methods and analysis The goal of the Glycemic Observation and Metabolic Outcomes in Mothers and Offspring study (GO MOMs) is to evaluate how early pregnancy glycaemia, measured using continuous glucose monitoring and oral glucose tolerance testing, relates to the diagnosis of gestational diabetes (GDM) at 24–28 weeks’ gestation (maternal primary outcome) and large-for-gestational-age birth weight (newborn primary outcome). Secondary objectives include relating early pregnancy glycaemia to other adverse pregnancy outcomes and comprehensively detailing longitudinal changes in glucose over the course of pregnancy. GO MOMs enrolment began in April 2021 and will continue for 3.5 years with a target sample size of 2150 participants.Ethics and dissemination GO MOMs is centrally overseen by Vanderbilt University’s Institutional Review Board and an Observational Study Monitoring Board appointed by National Institute of Diabetes and Digestive and Kidney Diseases. GO MOMs has potential to yield data that will improve understanding of hyperglycaemia in pregnancy, elucidate better approaches for early pregnancy GDM screening, and inform future clinical trials of early GDM treatment.Trial registration number NCT04860336.

Background: Cerebral small vessel disease is the most common cause of lacunar strokes (LS). Understanding LS pathogenesis is vital for predicting disease severity, prognosis, and developing therapies. Objectives: To research molecular profiles that differentiate LS in deep brain structures from those in subcortical white matter. Design: Prospective case–control study involving 120 patients with imaging-confirmed LS and a 120 control group. Methods: We examined the relationship between Alzheimer’s disease biomarkers [amyloid beta (Aβ 1–40 , Aβ 1–42 )], serum inflammatory marker (interleukin-6, IL-6), and endothelial dysfunction markers [soluble tumor necrosis factor-like weak inducer of apoptosis, and pentraxin-3 (sTWEAK, PTX3)] with respect to LS occurring in deep brain structures and subcortical white matter. In addition, we investigated links between LS, leukoaraiosis presence (white matter hyperintensities, WMHs), and functional outcomes at 3 months. Poor outcome was defined as a modified Rankin scale >2 at 3 months. Results: Significant differences were observed in levels of IL-6, PTX3, and sTWEAK between patients with deep lacunar infarcts and those with recent small subcortical infarcts (20.8 versus 15.6 pg/mL, p

IntroductionDynamic susceptibility-weighted contrast-enhanced (DSC) perfusion studies in magnetic resonance imaging (MRI) provide valuable data for studying vascular cerebral pathophysiology in different rodent models of brain diseases (stroke, tumor grading, and neurodegenerative models). The extraction of these hemodynamic parameters via DSC-MRI is based on tracer kinetic modeling, which can be solved using deconvolution-based methods, among others. Most of the post-processing software used in preclinical studies is home-built and custom-designed. Its use being, in most cases, limited to the institution responsible for the development. In this study, we designed a tool that performs the hemodynamic quantification process quickly and in a reliable way for research purposes.MethodsThe DSC-MRI quantification tool, developed as a Python project, performs the basic mathematical steps to generate the parametric maps: cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), signal recovery (SR), and percentage signal recovery (PSR). For the validation process, a data set composed of MRI rat brain scans was evaluated: i) healthy animals, ii) temporal blood–brain barrier (BBB) dysfunction, iii) cerebral chronic hypoperfusion (CCH), iv) ischemic stroke, and v) glioblastoma multiforme (GBM) models. The resulting perfusion parameters were then compared with data retrieved from the literature.ResultsA total of 30 animals were evaluated with our DSC-MRI quantification tool. In all the models, the hemodynamic parameters reported from the literature are reproduced and they are in the same range as our results. The Bland–Altman plot used to describe the agreement between our perfusion quantitative analyses and literature data regarding healthy rats, stroke, and GBM models, determined that the agreement for CBV and MTT is higher than for CBF.ConclusionAn open-source, Python-based DSC post-processing software package that performs key quantitative perfusion parameters has been developed. Regarding the different animal models used, the results obtained are consistent and in good agreement with the physiological patterns and values reported in the literature. Our development has been built in a modular framework to allow code customization or the addition of alternative algorithms not yet implemented.

Background: One of the main biological mechanisms behind the link between periodontitis and atherosclerotic vascular diseases is vascular endothelial dysfunction. Particularly, circulating endothelial progenitor cells (EPCs) have been considered a biomarker of altered vascular endothelial function. Objectives: The aim of this study was to investigate relationship between periodontal inflammation and increased number of circulating EPCs. Design: This is retrospective cohort study. Methods: In this study, 85 elderly patients with a previous history of hypertension were followed up to 12 months. A baseline full-mouth periodontal assessment was carried out, and the amount of periodontal tissue inflamed per subject was calculated as a proxy of periodontal inflammation [periodontal inflamed surface area (PISA)]. The number of circulating EPCs (CD34 + /CD133 + /KDR + ) was determined by flow cytometry from peripheral blood samples collected at baseline and 12 months. Results: Mean concentrations of CD34 + /CD133 + /KDR + progenitor cells were higher in periodontitis patients than in those without periodontitis at baseline [55.4, 95% confidence interval (CI) = 20.8 to 90.0 versus 27.2, 95% CI = 13.6 to 40.8, p = 0.008] and 12 months (114.6, 95% CI = 53.5 to 175.7 versus 19.1, 95% CI = 10.8 to 27.4, p = 0.003). A significant increase over the follow-up was noticed in the group of subjects with periodontitis ( p = 0.049) but not in the nonperiodontitis group ( p = 0.819). PISA was independently associated with CD34 + /CD133 + /KDR + EPCs at baseline ( B coefficient = 0.031, 95% CI = 0.005 to 0.058; p = 0.021). The relationship between PISA and CD34 + /CD133 + /KDR + EPCs at 12 months was confounded by increased baseline body mass index ( B coefficient = 0.064, 95% CI = −0.005 to 0.132; p = 0.066). Conclusion: Periodontal inflammation is associated with high number of CD34 + /CD133 + /KDR + EPCs, thus supporting a potential link between periodontitis and endothelial dysfunction.

Abstract Background Wake-up ischemic stroke (IS) has been usually excluded from acute stroke therapy options for being outside of the safe treatment window. We identified risk factors, and clinical or molecular biomarkers that could be therapeutic targets for wake-up stroke prevention, thus hopefully leading to a decrease in its mortality and disability in medium to long-term outcome. Methods 4251 ischemic stroke (IS) patients from a prospectively registered database were recruited; 3838 (90.3%) had known onset-symptom time, and 413 (9.7%) were wake-up strokes. The main endpoint was to analyze the association between different serum biomarkers with wake-up IS episodes and their progression. Leukocytes count, serum levels of C-reactive protein, fibrinogen, interleukin 6 (IL-6), and vitamin D were analyzed as inflammation biomarkers; N-terminal pro-B-type Natriuretic-Peptide and microalbuminuria, used as atrial/endothelial dysfunction biomarkers; finally, glutamate levels as excitotoxicity biomarker. In addition, demographic, clinical and neuroimaging variables associated with the time-evolution of wake-up IS patients and functional outcome at 3 months were evaluated. Good and poor functional outcome were defined as mRS ≤2 and mRS > 2 at 3 months, respectively. Results Wake-up IS showed a poorer outcome at 3-months than in patients with known on-set-symptom time (59.1% vs. 48.1%; p

Abstract Objective Leukoaraiosis (LA) refers to white matter lesions of undetermined etiology associated with the appearance and worsening of vascular pathologies. The aim is to confirm an increased frequency and intensity of LA in symptomatic patients with neurovascular pathology compared with asymptomatic subjects, and its association with circulating serum levels of soluble tumor necrosis factor‐like weak inducer of apoptosis (sTWEAK). Methods An observational study was conducted in which two groups of patients were compared. Group I (N = 242) comprised of asymptomatic subjects with arterial hypertension and/or diabetes or with a history of transient ischemic attacks, and Group II (N = 382) comprised patients with lacunar stroke or deep hemispheric intracerebral hemorrhage (ICH) of hypertensive origin. Serum levels of sTWEAK were analyzed and correlated with prevalence and intensity of LA according to the Fazekas scale. Results The prevalence of LA was higher in symptomatic (85.1%) versus asymptomatic patients (62.0%). Logistic regression model showed a significant relation of LA with neurovascular pathologies (OR: 2.69, IC 95%: 1.10–6.59, p = 0.003). When stratified according to the Fazekas scale, LA of grade II (OR: 3.53, IC 95%: 1.10–6.59, p = 0.003) and specially grade III (OR: 4.66, 95% CI: 1.09–19.84, p = 0.037) showed correlation with neurovascular pathologies. Increased sTWEAK levels were found in the symptomatic group in all LA grades (p

Abstract Background Ischemic stroke is the most common cerebrovascular disease and is caused by interruption of blood supply to the brain. To date, recombinant tissue plasminogen activator (rtPA) has been the main pharmacological treatment in the acute phase. However, this treatment has some drawbacks, such as a short half-life, low reperfusion rate, risk of hemorrhagic transformations, and neurotoxic effects. To overcome the limitations of rtPA and improve its effectiveness, we recently designed sonosensitive sub-micrometric capsules (SCs) loaded with rtPA with a size of approximately 600 nm, synthesized using the layer-by-layer (LbL) technique, and coated with gelatine for clot targeting. In this study, we evaluated the rtPA release of ultrasound (US)-responsive SCs in healthy mice and the therapeutic effect in a thromboembolic stroke model. Results In healthy mice, SCs loaded with rtPA 1 mg/kg responded properly to external US exposure, extending the half-life of the drug in the blood stream more than the group treated with free rtPA solution. The gelatine coating also contributed to stabilizing the encapsulation and maintaining the response to US. When the same particles were administered in the stroke model, these SCs appeared to aggregate in the ischemic brain region, probably generating secondary embolisms and limiting the thrombolytic effect of rtPA. Despite the promising results of these thrombolytic particles, at least under the dose and size conditions used in this study, the administration of these capsules represents a risk factor for stroke. Conclusions This is the first study to report the aggregation risk of a drug carrier in neurological pathologies such as stroke. Biocompatibility analysis related to the use of nano-and microparticles should be deeply studied to anticipate the limitations and orientate the design of new nanoparticles for translation to humans. Graphical Abstract

We present a case study of the periodized training by a world-class 400-m Individual Medley (IM) swimmer (4th in 2019 World Championships) in the season leading to a bronze medal in the 2018 European Championship. The complexity of this IM preparation was based on the experiences, observations and innovations of an Olympic swimming coach. Over 52 weeks, a traditional periodization model was employed using three macrocycles. A total of 15 competitions were completed in the season increasing in frequency in the third macrocycle. The training intensity distribution (TID) followed the pattern of a traditional pyramidal model in general training and polarized and threshold models during specifictraining before competitions. Weekly training volume ranged from 25 to 79 km, 24 to 87 km, and 25 to 90 km in each of the three macrocyles. Altitude training comprised 23% of total training weeks. Haemoglobin [Hb] increased from 14.9 to 16.0 g/100 ml and haematocrit from 45.1 to 48.1% after altitude training. Heart rate (HR) and [La- ] decreased at submaximal swimming intensities, while swimming velocity increased in the 8×100 m incremental swimming test in A2(1.4%) and in AT (0.6%). Pull up power was increased 10% through the season.

Ischemic stroke is becoming one of the most common causes of death and disability in developed countries. Since current therapeutic options are quite limited, focused on acute reperfusion therapies that are hampered by a very narrow therapeutic time window, it is essential to discover novel treatments that not only stop the progression of the ischemic cascade during the acute phase, but also improve the recovery of stroke patients during the sub-acute or chronic phase. In this regard, several studies have shown that endothelial progenitor cells (EPCs) can repair damaged vessels as well as generate new ones following cerebrovascular damage. EPCs are circulating cells with characteristics of both endothelial cells and adult stem cells presenting the ability to differentiate into mature endothelial cells and self-renew, respectively. Moreover, EPCs have the advantage of being already present in healthy conditions as circulating cells that participate in the maintenance of the endothelium in a direct and paracrine way. In this scenario, EPCs appear as a promising target to tackle stroke by self-promoting re-endothelization, angiogenesis and vasculogenesis. Based on clinical data showing a better neurological and functional outcome in ischemic stroke patients with higher levels of circulating EPCs, novel and promising therapeutic approaches would be pharmacological treatment promoting EPCs-generation as well as EPCs-based therapies. Here, we will review the latest advances in preclinical as well as clinical research on EPCs application following stroke, not only as a single treatment but also in combination with new therapeutic approaches.

Introducción: Las metástasis cerebrales (MC) representan una problemática importante de la salud pública, en promedio el 30% de los pacientes oncológicos desarrollarán MC siendo importante causa de morbilidad, ansiedad y mortalidad. El tratamiento con radioterapia, cirugía y sistémico son los pilares para el tratamiento y han tenido una evolución importante en la última década. Propósito de la revisión: Se proporciona información actualizada en relación a epidemiología, diagnóstico, pronóstico y tratamiento de metástasis cerebrales desde un enfoque multidisciplinario para lograr individualizar su abordaje con el objetivo de proporcionar control oncológico y calidad de vida. También se discuten el acceso a nuevas terapias sistémicas, técnicas quirúrgicas y disponibilidad de tecnología para ofrecer técnicas avanzadas de radioterapia. Mensaje principal: Conocer mutaciones específicas y receptores diana de los tumores permite elegir quimio-inmunoterapia o terapias dirigidas actuales que ofrecen mejor potencial de control tanto a nivel sistémico como intracraneal. La secuenciación de los tratamientos sistémicos y locales (cirugía, radiocirugía, radioterapia holocraneal) deben ser discutidos desde un enfoque multidisciplinario. Conclusión: Es importante poder estimar el pronóstico de los pacientes con MC, esto determinará la conducta terapéutica que puede variar desde cuidados sintomáticos hasta tratamientos más agresivos como resección neuroquirúrgica o radiocirugía.

BackgroundOccult atrial fibrillation (AF) is one of the major causes of embolic stroke of undetermined source (ESUS). Knowing the underlying etiology of an ESUS will reduce stroke recurrence and/or unnecessary use of anticoagulants. Understanding cardioembolic strokes (CES), whose main cause is AF, will provide tools to select patients who would benefit from anticoagulants among those with ESUS or AF. We aimed to discover novel loci associated with CES and create a polygenetic risk score (PRS) for a more efficient CES risk stratification.MethodsMultitrait analysis of GWAS (MTAG) was performed with MEGASTROKE-CES cohort (n = 362,661) and AF cohort (n = 1,030,836). We considered significant variants and replicated those variants with MTAG p-value < 5 × 10−8 influencing both traits (GWAS-pairwise) with a p-value < 0.05 in the original GWAS and in an independent cohort (n = 9,105). The PRS was created with PRSice-2 and evaluated in the independent cohort.ResultsWe found and replicated eleven loci associated with CES. Eight were novel loci. Seven of them had been previously associated with AF, namely, CAV1, ESR2, GORAB, IGF1R, NEURL1, WIPF1, and ZEB2. KIAA1755 locus had never been associated with CES/AF, leading its index variant to a missense change (R1045W). The PRS generated has been significantly associated with CES improving discrimination and patient reclassification of a model with age, sex, and hypertension.ConclusionThe loci found significantly associated with CES in the MTAG, together with the creation of a PRS that improves the predictive clinical models of CES, might help guide future clinical trials of anticoagulant therapy in patients with ESUS or AF.

Abstract We research into the clinical, biochemical and neuroimaging factors associated with the outcome of stroke patients to generate a predictive model using machine learning techniques for prediction of mortality and morbidity 3-months after admission. The dataset consisted of patients with ischemic stroke (IS) and non-traumatic intracerebral hemorrhage (ICH) admitted to Stroke Unit of a European Tertiary Hospital prospectively registered. We identified the main variables for machine learning Random Forest (RF), generating a predictive model that can estimate patient mortality/morbidity according to the following groups: (1) IS + ICH, (2) IS, and (3) ICH. A total of 6022 patients were included: 4922 (mean age 71.9 ± 13.8 years) with IS and 1100 (mean age 73.3 ± 13.1 years) with ICH. NIHSS at 24, 48 h and axillary temperature at admission were the most important variables to consider for evolution of patients at 3-months. IS + ICH group was the most stable for mortality prediction [0.904 ± 0.025 of area under the receiver operating characteristics curve (AUC)]. IS group presented similar results, although variability between experiments was slightly higher (0.909 ± 0.032 of AUC). ICH group was the one in which RF had more problems to make adequate predictions (0.9837 vs. 0.7104 of AUC). There were no major differences between IS and IS + ICH groups according to morbidity prediction (0.738 and 0.755 of AUC) but, after checking normality with a Shapiro Wilk test with the null hypothesis that the data follow a normal distribution, it was rejected with W = 0.93546 (p-value

Ischemic stroke, caused by the interruption of blood flow to the brain and subsequent neuronal death, represents one of the main causes of disability in worldwide. Although reperfusion therapies have shown efficacy in a limited number of patients with acute ischemic stroke, neuroprotective drugs and recovery strategies have been widely assessed, but none of them have been successful in clinical practice. Therefore, the search for new therapeutic approaches is still necessary. Sphingolipids consist of a family of lipidic molecules with both structural and cell signaling functions. Regulation of sphingolipid metabolism is crucial for cell fate and homeostasis in the body. Different works have emphasized the implication of its metabolism in different pathologies, such as diabetes, cancer, neurodegeneration, or atherosclerosis. Other studies have shown its implication in the risk of suffering a stroke and its progression. This review will highlight the implications of sphingolipid metabolism enzymes in acute ischemic stroke.

Introducción: La relación entre supervivencia e infiltración linfocitaria en el cáncer gástrico se ha determinado como factor pronóstico beneficioso, este estudio local tiene como objetivo determinar la probabilidad de supervivencia en los pacientes con cáncer gástrico estadios IB al IIIC de acuerdo con el porcentaje de infiltración linfocitaria. Metodología: El presente estudio longitudinal se realizó en el Hospital Oncológico Solón Espinosa Ayala Solca-Núcleo de Quito. El período de estudio de enero del 2013 a enero del 2016, el tiempo de seguimiento terminó en diciembre del 2018. El cálculo muestral fue no probabilístico en donde se incluyeron casos de pacientes mayores a 18 años con diagnóstico de cáncer gástrico con estadios clínicos IB al IIIC, que contaron con una muestra histopatológica de gastrectomías. Se usó la variable: “Porcentaje de infiltración” para el análisis la muestra y se dividió en 3 grupos: G1: infiltración linfocitaria leve, G2: moderada y G3: intensa. Las estimaciones de supervivencia se calcularon utilizando el método de Kaplan-Meier y la comparación entre los grupos con la prueba log-rank. Resultados: 173 pacientes con cáncer gástrico con estadios clínicos IB al IIIC, seguidos a 72 meses, el 60 % son hombres y el 40 % mujeres. Según el porcentaje de infiltración linfocitaria, el 52 % reportaron un porcentaje de infiltración leve, el 21 % moderada y el 27 % intensa. A los 72 meses de seguimiento la supervivencia en G1 fue del 31 %, en G2 fue del 48 %, y en G3 fue del 77 % (P= 0.001). Conclusión: Se encontró que el grado de infiltración linfocitaria intensa en los pacientes con cáncer gástrico estuvo asociado a una mejor supervivencia en el seguimiento a 72 meses.

La privación de sueño es la condición de insuficiencia de sueño, pudiendo ser crónica o aguda. Se investigó el efecto de la privación del sueño en el desempeño académico, mediante la aplicación de una encuesta. Específicamente, se investigó: cómo afecta el no dormir al rendimiento universitario. Para lograr esto, también se identificaron las partes del cerebro que se relacionan al sueño y describen las consecuencias causadas por la falta de sueño. Además, se analiza el patrón de sueño en los individuos universitarios. Dentro de los resultados se evaluó la veracidad de la hipótesis propuesta, que entre más tiempo de descanso tienen los estudiantes, mejores son los resultados en sus estudios. Sin embargo, los resultados de la investigación arrojaron que los estudiantes que duermen menos tiempo de igual manera consiguen mantener resultados aceptables. El rendimiento de la mayoría de los estudiantes universitarios no se ve alterado de gran manera por la privación de sueño, pero es mejor tener buenos hábitos de sueño, para poder evitar enfermedades que pueden adquirir en un futuro.

Los juegos de estrategia siempre han sido muy gustados por las personas. Juegos como el ajedrez y las damas, por mencionar algunos muy jugados. Han creado rivalidad entre jugadores y hasta se han convertido en deportes jugados por profesionales. Con el surgir de la inteligencia artificial se abre una nueva ventana para probar si las computadoras pueden superar a los humanos. De estas ideas han surgido algoritmos que buscan solucionar problemas a través de diferentes estrategias. En este artículo se estudiaron los algoritmos de minimax y alfa-beta, su definición, funcionalidad y complejidad. Estos algoritmos se implementaron en la emulación del juego de Lara Croft Go, que fue programado en el lenguaje de Java utilizando el IDE de NetBeans. La aplicación consiste en un juego donde un humano se enfrenta a una IA que fue programada con ambos algoritmos y se define por diferentes factores, quien es el mejor resolviendo el juego. La recolección de los datos es definida por los movimientos que realice cada algoritmo para completar los niveles y la cantidad de estados que genere en la búsqueda de la solución. Basados en los datos recopilados durante la ejecución de los algoritmos, se demuestra que el algoritmo más eficiente en la búsqueda de la solución de los niveles implementados es el algoritmo de búsqueda Alfa-Beta, ya que genera menos estados, por lo tanto, evalúa menos nodos y llega a una solución en un tiempo menor que el algoritmo de búsqueda Minimax.

Abstract Objective To investigate whether elevated serum levels of sTWEAK (soluble tumor necrosis factor‐like inducer of apoptosis) might be involved in a higher frequency of symptomatic hemorrhagic transformation (HT) through the presence of leukoaraiosis (LA) in patients with acute ischemic stroke (IS) undergoing reperfusion therapies. Methods This is a retrospective observational study. The primary endpoint was to study the sTWEAK‐LA‐HT relationship by comparing results with biomarkers associated to HT and evaluating functional outcome at 3‐months. Clinical factors, neuroimaging variables and biomarkers associated to inflammation, endothelial/atrial dysfunction or blood‐brain barrier damage were also investigated. Results We enrolled 875 patients (mean age 72.3 ± 12.2 years; 46.0% women); 710 individuals underwent intravenous thrombolysis, 87 endovascular therapy and 78 both. HT incidence was 32%; LA presence was 75.4%. Patients with poor functional outcome at 3‐months showed higher sTWEAK levels at admission (9844.2 [7460.4–12,542.0] vs. 2717.3 [1489.7–5852.3] pg/mL, P

Abstract Background Recent preclinical studies have shown that regulatory T cells (Treg) play a key role in the immune response after ischemic stroke (IS). However, the role of Treg in human acute IS has been poorly investigated. Our aim was to study the relationship between circulating Treg and outcome in human IS patients. Methods A total of 204 IS patients and 22 control subjects were recruited. The main study variable was good functional outcome at 3 months (modified Rankin scale ≤2) considering infarct volume, Early Neurological Deterioration (END) and risk of infections as secondary variables. The percentage of circulating Treg was measured at admission, 48, 72 h and at day 7 after stroke onset. Results Circulating Treg levels were higher in IS patients compared to control subjects. Treg at 48 h were independently associated with good functional outcome (OR, 3.5; CI: 1.9–7.8) after adjusting by confounding factors. Patients with lower Treg at 48 h showed higher frequency of END and risk of infections. In addition, a negative correlation was found between circulating Treg at 48 h (r = − 0.414) and 72 h (r = − 0.418) and infarct volume. Conclusions These findings suggest that Treg may participate in the recovery of IS patients. Therefore, Treg may be considered a potential therapeutic target in acute ischemic stroke.

ObjectiveThis study aimed to explore the association between smoking habit and the serum levels of soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK), in relation with the functional outcome of patients with acute ischemic stroke undergoing reperfusion treatment.MethodsObservational and retrospective study of a series of patients with acute ischemic stroke subjected to reperfusion treatments. Clinical, analytical, and neuroimaging parameters were analyzed. The main endpoint was the functional outcome at 3 months, measured by the modified Ranking Scale (mRS). Logistic regression models were used to analyze the association between smoking and sTWEAK levels with functional outcome and leukoaraiosis.ResultsThe results showed that smoking habit was associated with a good functional outcome at 3 months in patients with stroke (OR: 3.52; 95% CI: 1.03–11.9; p = 0.044). However, this independent association was lost after adjusting by sTWEAK levels (OR 1.73; 95% CI: 0.86–13.28; p = 0.116). sTWEAK levels were significantly lower in smoker patients [4015.5 (973.66–7921.83) pg/ml vs. 5,628 (2,848–10,202) pg/ml, p < 0.0001], while sTWEAK levels were significantly higher in patients with poor functional outcomes at 3 months [10,284 (7,388–13.247) pg/ml vs. 3,405 (2,329–6,629) pg/ml, p < 0.0001].ConclusionThe decrease in sTWEAK levels was associated with a good functional outcome in smoker patients with stroke undergoing reperfusion therapy.

Alzheimer’s disease (AD) is a neurodegenerative disease representing the most common type of dementia worldwide. The early diagnosis of AD is very difficult to achieve due to its complexity and the practically unknown etiology. Therefore, this is one of the greatest challenges in the field in order to develop an accurate therapy. Within the different etiological hypotheses proposed for AD, we will focus on the two-hit vascular hypothesis and vascular alterations occurring in the disease. According to this hypothesis, the accumulation of β-amyloid protein in the brain starts as a consequence of damage in the cerebral vasculature. Given that there are several vascular and angiogenic alterations in AD, and that endothelial progenitor cells (EPCs) play a key role in endothelial repair processes, the study of EPCs in AD may be relevant to the disease etiology and perhaps a biomarker and/or therapeutic target. This review focuses on the involvement of endothelial dysfunction in the onset and progression of AD with special emphasis on EPCs as a biomarker and potential therapeutic target.

Aunque la figura de paisaje cultural es la más utilizada para proceder al reconocimiento y actuación sobre los espacios agrarios, ésta presenta importantes carencias en aspectos fundamentales como la delimitación de dichos espacios o los mecanismos y medidas establecidos para su protección. Para poder avanzar en la mejora de estas deficiencias es necesario aplicar sobre los paisajes culturales agrarios los principios que rigen el Patrimonio Agrario, que es el marco conceptual que debería guiar cualquier actuación sobre los bienes agrarios, incluidos los paisajes culturales, que no son más que un instrumento legal, una tipología de bien inmueble (tal y como intentamos demostrar al principio de nuestro artículo), para abordar la tutela de la dimensión territorial (por otro lado, la más importante) de los bienes agrícolas, ganaderos y silvícolas.

Alzheimer’s disease (AD) is the most common degenerative disorder in the elderly in developed countries. Currently, growing evidence is pointing at endothelial dysfunction as a key player in the cognitive decline course of AD. As a main component of the blood–brain barrier (BBB), the dysfunction of endothelial cells driven by vascular risk factors associated with AD allows the passage of toxic substances to the cerebral parenchyma, producing chronic hypoperfusion that eventually causes an inflammatory and neurotoxic response. In this process, the levels of several biomarkers are disrupted, such as an increase in adhesion molecules that allow the passage of leukocytes to the cerebral parenchyma, increasing the permeability of the BBB; moreover, other vascular players, including endothelin-1, also mediate artery inflammation. As a consequence of the disruption of the BBB, a progressive neuroinflammatory response is produced that, added to the astrogliosis, eventually triggers neuronal degeneration (possibly responsible for cognitive deterioration). Recently, new molecules have been proposed as early biomarkers for endothelial dysfunction that can constitute new therapeutic targets as well as early diagnostic and prognostic markers for AD.

Recanalization of the occluded artery is the gold standard treatment for acute ischemic stroke, which includes enzymatic fibrinolytic treatment with the use of recombinant tissue plasminogen activators (rtPAs) to disrupt the occluding clot, the use of mechanical thrombectomy to physically remove the clot, or a combination of both. Fibrin is one of the main components of blood clots causing ischemic stroke and is the target of rtPA upon activation of plasminogen in the clot. In addition, fibrin content also influences the efficacy of mechanical thrombectomy. Current imaging methods can successfully identify occlusions in large vessels; however, there is still a need for contrast agents capable of visualizing small thrombi in ischemic stroke patients. In this work, we describe the synthesis and the in vitro characterization of a new diagnostic nanoparticle, as well as the in vivo evaluation in an animal model of thromboembolic stroke. Gd-labeled KCREKA peptides were synthesized and attached onto the surface of PEGylated superparamagnetic nanoparticles. Magnetic resonance imaging (MRI) of blood clots was performed in vitro and in vivo in animal models of thromboembolic stroke. KCREKA-NPs were synthesized by attaching the peptide to the amino (N) termini of the PEG-NPs. The sizes of the nanoparticles, measured via DLS, were similar for both KCREKA-NPs and PEG-NPs (23 ± 4 nm, PDI = 0.11 and 25 ± 8 nm, PDI = 0.24, respectively). In the same line, r2 relaxivities were also similar for the nanoparticles (149 ± 2 mM Fe s−1 and 151 ± 5 mM Fe s−1), whereas the r1 relaxivity was higher for KCREKA-NPs (1.68 ± 0.29 mM Fe s−1 vs. 0.69 ± 0.3 mM Fe s−1). In vitro studies showed that blood clots with low coagulation times were disrupted by rtPA, whereas aged clots were almost insensitive to the presence of rtPA. MRI in vitro studies showed a sharp decrease in the T1 × T2 signals measured for aged clots incubated with KCREKA-NPs compared with fresh clots (47% [22, 80] to 26% [15, 51]). Furthermore, the control blood showed a higher value of the T1 × T2 signal (39% [20, 61]), being the blood clots with low coagulation times the samples with the lowest values measured by MRI. In vivo studies showed a significant T1 × T2 signal loss in the clot region of 24% after i.v. injection of KCREKA-NPs. The thrombus age (2.5% ± 6.1% vs. 81.3% ± 19.8%, p < 0.01) confirmed our ability to identify in vivo fresh blood clots. In this study, we developed and tested a dual MRI nanoparticle, acting as T1 and T2 contrast agents in MRI analyses. The developed KCREKA-NPs showed affinity for the fibrin content of blood clots, and the MRI signals provided by the nanoparticles showed significant differences depending on the clot age. The developed KCREKA-NPs could be used as a tool to predict the efficacy of a recanalization treatment and improve the triage of ischemic stroke patients.

Gas exchange measurements were taken with an infrared gas analyzer (IRGA) and chlorophyll fluorescence with a modulated amplitude pulse fluorimeter (Mini-PAM) on fully developed leaves of ramon (Brosimum alicastrum Swartz) a tropical rainforest tree, grown in its natural habitat as to collect basic information of its physiological behavior. Data showed that maximum fixation of CO2 was 5 µmol m-2 s-1, photosynthetic efficiency was 0.67 while the photosystem II was found to saturate at a photonic flux density (PFD) of 500 µmol at 15 h. A high correlation was found between photosynthesis and transpiration. Highest water use efficiency occurred after 15 hours at a temperature of 30 °C, while chlorophyll levels remained constant. This is a shade tolerant, plant species thus it was found that initiates the photosynthetic process with low levels of light, presenting a light compensation point of 24 µmol m-2 s-1. In a parallel study, the same variables were measured in two sets of individuals of the same specie collected from two distant localities but growth in pots in the open. Photosynthetic variables of this plant species data showed very similar patterns. The results obtained suggest that, during the daylight hours and at higher temperatures, this species can carry out photosynthesis with high water use efficiency. Based on the results, the conclusion is that this plant species can adapt to a diversity of environmental conditions.

Background: Excitatory amino acid transporter 2 (EAAT2) plays a pivotal role in glutamate clearance in the adult brain, thereby preventing excitotoxic effects. Considering the high efficacy of EAAT2 for glutamate uptake, we hypothesized that the expression of this transporter in mesenchymal stem cells (MSCs) for systemic administration could yield a cell-based glutamate-grabbing therapy, combining the intrinsic properties of these cells with excitotoxic protection. Methods: To address this hypothesis, EAAT2-encoding cDNA was introduced into MSCs and human embryonic kidney 293 cells (HEK cells) as the control cell line. EAAT2 expression and functionality were evaluated by in vitro assays. Blood glutamate-grabbing activity was tested in healthy and ischemic rat models treated with 3 × 106 and 9 × 106 cells/animal. Findings: The expression of EAAT2 in both cell types conferred the expected glutamate-grabbing activity in in vitro and in vivo studies. The functional improvement observed in ischemic rats treated with EAAT2–HEK at low dose, confirmed that this effect was indeed mediated by the glutamate-grabbing activity associated with EAAT2 functionality. Unexpectedly, both cell doses of non-transfected MSCs induced higher protection than transfected EAAT2–MSCs by another mechanism independent of the glutamate-grabbing capacity. Interpretation: Although the transfection procedure most likely interferes with some of the intrinsic protective mechanisms of mesenchymal cells, the results show that the induced expression of EAAT2 in cells represents a novel alternative to mitigate the excitotoxic effects of glutamate and paves the way to combine this strategy with current cell therapies for cerebral ischemia. Keywords: Cell therapy, Cerebral ischemia, Excitatory amino acid transporter 2, Excitotoxic injury, Excitotoxic protection, Glutamate, Mesenchymal stem cells

En la actualidad existen una serie de tendencias en relación al patrimonio cultural que, si bien, de forma mayoritaria están siendo observadas como positivos y necesarios avances en la caracterización o actuación sobre el mismo, para nosotros encierran verdaderos peligros, que pueden acabar afectando muy seriamente a los fundamentos de la tutela del patrimonio cultural si su reconocimiento, tal y como parece se está desarrollando en la actualidad, no se hace acorde con dichos fundamentos. Aunque son muchas esas tendencias, y muy fragmentadas, nosotros nos vamos a centrar en las que han conseguido un mayor grado de asimilación y aceptación como son las del paisaje cultural, la salvaguardia del patrimonio cultural inmaterial, el concepto de comunidad o la memoria, sobre las que ofrecemos una mirada bastante diferente, quizás a contracorriente, de la ofrecida de forma general por la historiografía patrimonialista. Con ello pretendemos llamar la atención sobre lo que realmente es el objetivo final de este artículo: manifestar nuestra absoluta preocupación por el progresivo desmantelamiento que está experimentando nuestro sistema de tutela, para lo cual estas tendencias están ejerciendo el triste (aunque en la mayoría de los casos no sea intencionadamente) papel de coartadas para deslegitimar e invalidar dicho sistema.

Aim: The purpose of this study was to investigate clinical and neuroimaging factors associated with stroke recurrence in reperfused ischemic stroke patients, as well as the influence of specific biomarkers of inflammation and endothelial dysfunction.Methods: We conducted a retrospective analysis on a prospectively registered database. Of the 875 patients eligible for this study (53.9% males; mean age 69.6 ± 11.8 years vs. 46.1% females; mean age 74.9 ± 12.6 years), 710 underwent systemic thrombolysis, 87 thrombectomy and in 78, systemic or intra-arterial thrombolysis together with thrombectomy was applied. Plasma levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα) were analyzed as markers of inflammation, and soluble tumor necrosis factor-like inducer of apoptosis (sTWEAK) as an endothelial dysfunction marker. The main outcome variables of the study were the presence and severity of leukoaraiosis (LA) and stroke recurrence.Results: The average follow-up time of the study was 25 ± 13 months, during which 127 patients (14.5%) showed stroke recurrence. The presence and severity of LA was more severe in the second stroke episode (Grade III of the Fazekas 28.3 vs. 52.8%; p < 0.0001). IL-6 levels at the first admission and before reperfusion treatment in patients with and without subsequent recurrence were similar (9.9 ± 10.4 vs. 9.1 ± 7.0 pg/mL, p = 0.439), but different for TNFα (14.7 ± 5.6 vs. 15.9 ± 5.7 pg/mL, p = 0.031) and sTWEAK (5,970.8 ± 4,330.4 vs. 8,660.7 ± 5,119.0 pg/mL, p < 0.0001). sTWEAK values ≥7,000 pg/mL determined in the first stroke were independently associated to recurrence (OR 2.79; CI 95%: 1.87–4.16, p < 0.0001).Conclusions: The severity and the progression of LA are the main neuroimaging factors associated with stroke recurrence. Likewise, sTWEAK levels were independently associated to stroke recurrence, so further studies are necessary to investigate sTWEAK as a therapeutic target.

Dar respuesta a un planteamiento inicial como ¿qué éxito tienen los escolares extranjeros que han pasado por las ATAL? es la singularidad de este artículo. Con todo, las ATAL son un recurso educativo de la Consejería de Educación de la Junta de Andalucía, que a su vez está vinculada a través de diversas medidas contempladas y programadas por el Plan Andaluz de Educación de Inmigrantes (PAEI). Asimismo, esta investigación es el resultado de otras tantas ya concluidas, así como de un proyecto iniciado recientemente en el marco del Plan Nacional de I+D+i y que pretende estudiar las trayectorias escolares del alumnado “extranjero” en comparación con el alumnado autóctono.

Este libro recoge los contenidos más relevantes de la tesis doctoral Conjuntos Históricos de Granada: Delimitación, planeamiento y rehabilitación (1985-2015) realizada por el arquitecto Gabriel Jesús Fernández Adarve y defendida públicamente con la máxima calificación en 2018.

Uno de los intereses científicos y objeto de sus últimas investigaciones de la profesora de Historia del Arte de la Universidad de Zaragoza, Ascensión Hernández Martínez, es la restauración monumental y, en general, la protección del patrimonio históricoartístico en la amplia etapa del franquismo. Es en este contexto en el que se enmarca esta publicación de la Universidad de Zaragoza, en la que analiza un aspecto especialmente relevante y poco conocido hasta ahora de uno de los personajes cruciales (ya que supera con creces la simple condición de arquitecto restaurador o estudioso de la historia de la arquitectura) de este periodo como es Fernando Chueca Goitia, al que la autora ya le ha dedicado varios trabajos. Esta faceta a la que nos referimos es la de su actividad o más bien pensamiento en torno a la protección de las ciudades históricas que, como ahora veremos, él la aborda sobre todo desde la denuncia de su masiva y vergonzosa destrucción en las décadas de los sesenta y setenta del siglo XX, que es en el contexto histórico en el que Chueca escribe los textos objeto de análisis en esta publicación.

Modern surgical education is focused on making use of the available technologies in order to train and assess surgical skill acquisition. Innovative technologies for the automatic, objective assessment of nontechnical skills are currently under research. The main aim of this study is to determine whether personal resourcefulness can be assessed by monitoring parameters that are related to stress and visual attention and whether there is a relation between these and psychomotor skills in surgical education. For this purpose, we implemented an application in order to monitor the electrocardiogram (ECG), galvanic skin response (GSR), gaze and performance of surgeons-in-training while performing a laparoscopic box-trainer task so as to obtain technical and personal resourcefulness’ metrics. Eight surgeons (6 nonexperts and 2 experts) completed the experiment. A total of 22 metrics were calculated (7 technical and 15 related to personal resourcefulness) per subject. The average values of these metrics in the presence of stressors were compared with those in their absence and depending on the participants’ expertise. The results show that both the mean normalized GSR signal and average surgical instrument’s acceleration change significantly when stressors are present. Additionally, the GSR and acceleration were found to be correlated, which indicates that there is a relation between psychomotor skills and personal resourcefulness.

Abstract Background Studying the impact of demographic changes and progress in the management of stroke patients is necessary in order to organize care structures for the coming years. Consequently, we analyzed the prognostic trends of patients admitted to the Stroke Unit of a tertiary hospital in the last ten years. Methods The University Clinical Hospital of Santiago de Compostela is the referral hospital for stroke in a catchment area that accounts for 16.5% of the population of Galicia. Data from patients admitted to the Stroke Unit were registered prospectively. A multinomial logistic regression was performed to determine the influence of new trends in demographic factors and in the management of patients with acute stroke. For the expected trend of progression, a 2008–2011 and 2012–2017 time series model was made by selecting the most appropriate model. Results In the last 10 years, the age of stroke onset has only increased in women (from 74.4 ± 2.2 years in 2008 to 78.8 ± 2.1 years in 2017; p = 0.037), and the same happens with the severity of neurological symptoms (ischemic stroke (IS), p

Despite transferrin being the main circulating carrier of iron in body fluids, and iron overload conditions being known to worsen stroke outcome through reactive oxygen species (ROS)-induced damage, the contribution of blood transferrin saturation (TSAT) to stroke brain damage is unknown. The objective of this study was to obtain evidence on whether TSAT determines the impact of experimental ischemic stroke on brain damage and whether iron-free transferrin (apotransferrin, ATf)-induced reduction of TSAT is neuroprotective. We found that experimental ischemic stroke promoted an early extravasation of circulating iron-loaded transferrin (holotransferrin, HTf) to the ischemic brain parenchyma. In vitro, HTf was found to boost ROS production and to be harmful to primary neuronal cultures exposed to oxygen and glucose deprivation. In stroked rats, whereas increasing TSAT with exogenous HTf was detrimental, administration of exogenous ATf and the subsequent reduction of TSAT was neuroprotective. Mechanistically, ATf did not prevent extravasation of HTf to the brain parenchyma in rats exposed to ischemic stroke. However, ATf in vitro reduced NMDA-induced neuronal uptake of HTf and also both the NMDA-mediated lipid peroxidation derived 4-HNE and the resulting neuronal death without altering Ca2+-calcineurin signaling downstream the NMDA receptor. Removal of transferrin from the culture media or blockade of transferrin receptors reduced neuronal death. Together, our data establish that blood TSAT exerts a critical role in experimental stroke-induced brain damage. In addition, our findings suggest that the protective effect of ATf at the neuronal level resides in preventing NMDA-induced HTf uptake and ROS production, which in turn reduces neuronal damage.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form of hereditary stroke disorder. It is caused by mutations in NOTCH3 that lead to progressive degeneration of the smooth muscle cells in blood vessels. There is currently no treatment for this disorder. We reprogrammed to pluripotency blood mononuclear cells isolated from a patient carrying a NOTCH3 mutation by using a commercially available non-integrating system. The success in the generation of this iPSC line (IDISi001-A) suggests that the NOTCH3 mutation did not limit cell reprogramming and offers an unprecedented opportunity for studying and modeling CADASIL pathology.

Proper occlusion of the medial cerebral artery, as determined by laser Doppler monitoring, during cerebral ischaemia in rat models is an important inclusion criterion in experimental studies. However, successful occlusion of the artery does not always guarantee a reproducible infarct volume, which is crucial for validating the efficacy of new protective drugs. In a rat intraluminal ischaemic model, laser Doppler monitoring alone was compared with laser Doppler monitoring in combination with magnetic resonance angiography (MRA) and diffusion-weighted imaging (DWI). Twenty-eight animals showed successful occlusion and reperfusion determined with Doppler monitoring, with an infarct size at 24 h of 16.7±11.5% (determined as ischaemic damage with respect to the ipsilateral hemisphere volume). However, when arterial occlusion and infarct damage were analysed in these animals using MRA and DWI, respectively, 15 animals were excluded and only 13 animals were included, with an infarct size at 24 h of 21.6±6.1%, showing a variability in the infarct size significantly lower (P

Abstract Neurological diseases of diverse aetiologies have significant effects on the quality of life of patients. The limited self-repairing capacity of the brain is considered to be the origin of the irreversible and progressive nature of many neurological diseases. Therefore, neuroprotection is an important goal shared by many clinical neurologists and neuroscientists. In this review, we discuss the main obstacles that have prevented the implementation of experimental neuroprotective strategies in humans and propose alternative avenues for the use of neuroprotection as a feasible therapeutic approach. Special attention is devoted to nanotechnology, which is a new approach for developing highly specific and localized biomedical solutions for the study of the multiple mechanisms involved in stroke. Nanotechnology is contributing to personalized neuroprotection by allowing us to identify mechanisms, determine optimal therapeutic windows, and protect patients from brain damage. In summary, multiple aspects of these new players in biomedicine should be considered in future in vivo and in vitro studies with the aim of improving their applicability to clinical studies.

Intracerebral hemorrhage (ICH) is the most severe cerebrovascular disease, which represents a leading cause of death and disability in developed countries. However, therapeutic options are limited, so is mandatory to investigate repairing processes after stroke in order to develop new therapeutic strategies able to promote brain repair processes. Therapeutic angiogenesis and vasculogenesis hold promise to improve outcome of ICH patients. In this regard, circulating endothelial progenitor cells (EPCs) have recently been suggested to be a marker of vascular risk and endothelial function. Moreover, EPC levels have been associated with good neurological and functional outcome as well as reduced residual hematoma volume in ICH patients. Finally, experimental and clinical studies indicate that EPC might mediate endothelial cell regeneration and neovascularization. Therefore, EPC-based therapy could be an excellent therapeutic option in ICH. In this mini-review, we discuss the present status of knowledge about the possible therapeutic role of EPCs in ICH, molecular mechanisms, and the future perspectives and strategies for their use in clinical practice.

Stroke is the main cause of disability and death in the world within neurological diseases. Despite such a huge impact, enzymatic, and mechanical recanalization are the only treatments available so far for ischemic stroke, but only

Photobiomodulation (PBM) therapy is a promising therapeutic approach for several pathologies, including stroke. The biological effects of PBM for the treatment of cerebral ischemia have previously been explored as a neuroprotective strategy using different light sources, wavelengths, and incident light powers. However, the capability of PBM as a novel alternative therapy to stimulate the recovery of the injured neuronal tissue after ischemic stroke has been poorly explored. The aim of this study was to investigate the low-level light irradiation therapy by using Light Emitting Diodes (LEDs) as potential therapeutic strategy for stroke. The LED photobiomodulation (continuous wave, 830 nm, 0.2–0.6 J/cm2) was firstly evaluated at different energy densities in C17.2 immortalized mouse neural progenitor cell lines, in order to observe if this treatment had any effect on cells, in terms of proliferation and viability. Then, the PBM-LED effect (continuous wave, 830 nm, 0.28 J/cm2 at brain cortex) on long-term recovery (12 weeks) was analyzed in ischemic animal model by means lesion reduction, behavioral deficits, and functional magnetic resonance imaging (fMRI). Analysis of cellular proliferation after PBM was significantly increased (1 mW) in all different exposure times used; however, this effect could not be replicated in vivo experimental conditions, as PBM did not show an infarct reduction or functional recovery. Despite the promising therapeutic effect described for PBM, further preclinical studies are necessary to optimize the therapeutic window of this novel therapy, in terms of the mechanism associated to neurorecovery and to reduce the risk of failure in futures clinical trials.

Identifying the complexities of the effect of sex on stroke risk, etiology, and lesion progression may lead to advances in the treatment and care of ischemic stroke (IS) and non-traumatic intracerebral hemorrhage patients (ICH). We studied the sex-related discrepancies on the clinical course of patients with IS and ICH, and we also evaluated possible molecular mechanisms involved. The study's main variable was the patient's functional outcome at 3-months. Logistic regression models were used in order to study the influence of sex on different inflammatory, endothelial and atrial dysfunction markers. We recruited 5,021 patients; 4,060 IS (54.8% male, 45.2% female) and 961 ICH (57.1% male, 42.9% female). Women were on average 5.7 years older than men (6.4 years in IS, 5.1 years in ICH), and more likely to have previous poor functional status, to suffer atrial fibrillation and to be on anticoagulants. IS patients showed sex-related differences at 3-months regarding poorer outcome (55.6% women, 43.6% men, p < 0.0001), but this relationship was not found in ICH (56.8% vs. 61.9%, p = 0.127). In IS, women had higher levels of NT-proBNP and 3-months worse outcome in both cardioembolic and non-cardioembolic stroke patients. Stroke patients showed sex-related differences in pre-hospital data, clinical variables and molecular markers, but only IS patients presented independent sex-related differences in 3-months poor outcome and mortality. There was a relationship between the molecular marker of atrial dysfunction NT-proBNP and worse functional outcome in women, resulting in a possible indicator of increased dysfunction.

El libro que presentamos se corresponde con una de las actividades realizadas en el contexto del Año Europeo del Patrimonio Cultural, que en el caso de la Universidad de Alcalá de Henares ha coincidido con otros dos importantísimos aniversarios, el del V Centenario de la muerte de su fundador, el Cardenal Cisneros, y el del 40 aniversario de la recuperación de la Universidad de Alcalá en el curso 1977-1978, la cual había sido cerrada y trasladada a mediados de siglo XIX a Madrid a pesar de su grandioso pasado.

El libro objeto de esta reseña ha sido publicado por la reputada Institución Fernando el Católico de la Diputación de Zaragoza (referencia ésta a la institución que en este caso tiene pleno sentido como ahora se verá) con motivo de la celebración del cincuenta aniversario de la declaración de Sos del Rey Católico como conjunto histórico-artístico, producida el 6 de junio de 1968. Esta efeméride ha sido tomada como referencia para reeditar dos textos publicados en la revista Zaragoza (en 1957 y 1970) por parte de los dos arquitectos que más trabajaron en el proceso de intervención (reconstrucción fundamentalmente) de esta magnífica villa zaragozana de origen (y persistencia) medieval, Teodoro Ríos Balaguer y Francisco Pons-Sorolla, el primero en la década de los cincuenta y el segundo en la de los sesenta.

Ceramide is a bioactive sphingolipid involved in numerous cellular processes. In addition to being the precursor of complex sphingolipids, ceramides can act as second messengers, especially when they are generated at the plasma membrane of cells. Its metabolic dysfunction may lead to or be a consequence of an underlying disease. Recent reports on transcriptomics and electrospray ionization mass spectrometry analysis have demonstrated the variation of specific levels of sphingolipids and enzymes involved in their metabolism in different neurodegenerative diseases. In the present review, we highlight the most relevant discoveries related to ceramide and neurodegeneration, with a special focus on Parkinson’s disease.

Previous studies have reported increased brain deposits of iron in patients with chronic migraine (CM). This study aims to determine the relation between iron deposits and outcome after treatment with OnabotulinumtoxinA (OnabotA). Demographic and clinical data were collected for this study through a prospective cohort study including 62 CM patients treated with OnabotA in the Hospital Clínico Universitario de Santiago de Compostela (Spain). Demographic and clinical variables were registered. Selected biomarkers in plasma during interictal periods (calcitonin gene-related peptide (CGRP) and pentraxin-3 (PTX3)) and neuroimaging changes (iron deposits in the red nucleus (RN), substantia nigra (SN), globus pallidus (GP), and periaqueductal gray matter (PAG), and white matter lesions (WML)) were determined. Subjects were classified in responders (≥50% reduction in headache days) or non-responders (p = 0.001), showed higher serum levels of CGRP (≥50 ng/mL) and PTX3 (≥1000 pg/mL) and smaller iron deposits in the GP and PAG (mean difference = 805.0; 95% CI: 37.9–1572.1 μL, p = 0.040 and mean difference = 69.8; 95% CI: 31.0–108.6 μL, p = 0.008; respectively). Differences in PAG iron deposits remained significant after adjusting for age (mean difference = 65.7; 95% CI: 22.8–108.6 μL, p = 0.003) and were associated with poor response to OnabotA after adjustment for clinical and biochemical variables (odds ratio (OR) = 0.963; 95% CI: 0.927–0.997, p = 0.041). We conclude that larger PAG iron deposits are associated with poor response to OnabotA in CM.