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Resumen Introduccion Las baterias neuropsicologicas empleadas tradicionalmente para el diagnostico del deterioro cognitivo (DC) en la esclerosis multiple son pruebas complejas que conllevan mucho tiempo. Se necesitan test mas simples para detectar el DC en la practica clinica diaria. Objetivo Evaluar la validez diagnostica y la fiabilidad de la escala Montreal Cognitive Assessment (MoCA) como herramienta de cribado de DC en la esclerosis multiple frente a la Bateria Neuropsicologica Breve. Material y metodos Se seleccionaron 52 pacientes (61,5% mujeres, edad media [desviacion estandar] 41,7 [11,5] anos). Se analizaron la fiabilidad (consistencia interna, interobservador y test-retest) y la validez de constructo (analisis factorial, coeficiente de correlacion de Pearson y coeficiente de determinacion) y de criterio (curva ROC, sensibilidad, especificidad, acuerdo global, valores predictivos positivo y negativo, cocientes de probabilidad positivo y negativo y nomograma de Fagan). Resultados La prevalencia de DC fue del 21,2% segun la Bateria Neuropsicologica Breve y del 25% segun el MoCA. El MoCA mostro buena consistencia interna (alfa de Cronbach 0,822) y buena fiabilidad interobservador y test-retest (coeficiente de correlacion intraclase de 0,80 y 0,96, respectivamente). El coeficiente de correlacion entre la puntuacion total de la Bateria Neuropsicologica Breve y el MoCA fue de 0,82. El punto optimo de corte en la curva ROC fue 25-26, con una sensibilidad del 91% y una especificidad del 93%. Conclusion El MoCA es una herramienta de cribado valida y fiable para la deteccion de DC en pacientes con esclerosis multiple.

Resumen Introduccion La ARCA1/SCAR8 es una heredoataxia recesiva causada por mutaciones en el gen SYNE1, que fue descrita inicialmente en familias francocanadienses (Quebec) con un sindrome cerebeloso puro. En la actualidad se reporta cada vez mas este tipo de ataxia en otras partes del mundo y con un fenotipo muy variable. Recientemente se han notificado casos de distrofia muscular, artrogriposis y miocardiopatia por mutaciones de este gen. Objetivos Describir los hallazgos clinicos y moleculares en 3 familias espanolas de diferente origen geografico, las primeras en las que se confirmo el diagnostico de ARCA1/SCAR8 con analisis molecular. Material y metodos Evaluacion clinica, pruebas paraclinicas y estudio genetico en 4 pacientes (3 varones y una mujer), diagnosticados en distintos servicios de neurologia espanoles. Resultados Los sintomas cerebelosos comenzaron en todos los casos en la tercera-cuarta decadas. Tras 15 anos de evolucion, 3 pacientes presentaban un sindrome cerebeloso puro similar a la descripcion original, mientras que un paciente con mas de 30 anos de evolucion presentaba tambien paralisis de mirada vertical, afectacion piramidal y moderado deterioro cognitivo. El estudio de resonancia magnetica mostro en todos los casos atrofia restringida al cerebelo. La secuenciacion de SYNE1 permitio identificar distintas variantes patogenicas en cada familia. Conclusiones La ARCA1/SCAR8 tiene una distribucion mundial con una gran diversidad de mutaciones en SYNE1. Ademas de ataxia puede dar lugar a un complejo fenotipo de inicio y gravedad muy variable.

Background: Controversy remains about the efficacy of tocilizumab (TCZ) for the treatment of severe COVID-19. We aimed to analyze the profile of TCZ-respondent patients. Methods: We retrospectively analyzed a cohort of patients with severe COVID-19 who received off-label TCZ after recommendation by a local committee and were admitted to the University Hospital “12 de Octubre” until May 2020. The primary end point was a significant clinical improvement (SCI) on day 14 after administration of TCZ. Factors independently related to SCI were analyzed by multivariate logistic regression models. Results: Of 428 (63.3%) patients treated with TCZ, 271 (63.3%) experienced SCI. After adjustment for factors related to unfavorable outcomes, TCZ administration within the first 48 hours from admission (odds ratio [OR]: 1.98, 95% confidence Interval [95% CI]: 1.1–3.55; P = 0.02) and ALT levels >100 UI/L at day 0 (OR: 3.28; 95% CI: 1.3–8.1; P = 0.01) were independently related to SCI. The rate of SCI significantly decreased according to the time of TCZ administration: 70.2% in the first 48 hours from admission, 58.5% on days 3-7, and 45.1% after day 7 (P = 0.03 and P = 0.001, respectively). Conclusion: TCZ improves the prognosis of patients with COVID-19 the most if treatment starts within the first 48 hours after admission.

Introduction: The main challenge of Parkinson’s disease in women of childbearing age is managing symptoms and drugs during pregnancy and breastfeeding. The increase in the age at which women are having children makes it likely that these pregnancies will become more common in future. Objectives: This study aims to define the clinical characteristics of women of childbearing age with Parkinson’s disease and the factors affecting their lives, and to establish a series of guidelines for managing pregnancy in these patients. Results: This consensus document was developed through an exhaustive literature search and a discussion of the available evidence by a group of movement disorder experts from the Spanish Society of Neurology. Conclusions: Parkinson’s disease affects all aspects of sexual and reproductive health in women of childbearing age. Pregnancy should be well planned to minimise teratogenic risk. A multidisciplinary approach should be adopted in the management of these patients in order to take all relevant considerations into account. Resumen: Introducción: El manejo de la enfermedad de Parkinson en la mujer en edad fértil nos plantea como principal reto el manejo de la enfermedad y los fármacos durante el embarazo y lactancia. El aumento de la edad gestacional de la mujer hace más probable que la incidencia de embarazos pueda incrementarse. Objetivo: Definir las características clínicas y los factores que condicionan la vida de la mujer en edad fértil con enfermedad de Parkinson y definir una guía de actuación y manejo del embarazo en estas pacientes. Desarrollo: Este documento de consenso se ha realizado mediante una búsqueda bibliográfica exhaustiva y discusión de los contenidos llevadas a cabo por un grupo de expertos en trastornos del movimiento de la Sociedad Española de Neurología. Conclusiones: La enfermedad de Parkinson afecta a todos los aspectos relacionados con la salud sexual y reproductiva de la mujer en edad fértil. Se debe planificar el embarazo en las mujeres con enfermedad de Parkinson para minimizar los riesgos teratogénicos sobre el feto. Se recomienda un abordaje multidisciplinar de estas pacientes para tener en cuenta todos los aspectos implicados.

The beneficial health effects of phytochemicals depend on their bioavailability and the form under which they reach systemic circulation, usually as phase II metabolites. The lack of authentic standards for these metabolites makes their quantification in biological samples challenging. A new analytical approach to get a more accurate quantification of oleuropein metabolites in biological samples after ingestion of olive leaf extract was proposed. This approach was based on the calculation of a response factor in QTOF MS for each metabolite, comparing their quantification in UV and MS using urine samples concentrated in the metabolites of interest. Glucuronide and sulfate conjugates of hydroxytyrosol and homovanillyl alcohol were more accurately quantified in plasma and urine and for the first time, oleuropein aglycone conjugates and their hydroxylated and hydrogenated derivatives were quantified after consumption of olive products. This approach could be extensible to the analysis of other phenolic metabolites when authentic standards are not available, opening a valuable method for bioavailability studies.

Different technologies commonly employed by the fruit processing industry affect the phenolic content. This study aimed to establish the extent to which different processing techniques and conditions, tested at an industrial scale, affect phenolics, color, and sensory attributes of fresh strawberries and apples. The effects of freezing, thermal treatments, and high-pressure processing were investigated. In strawberries, mild and standard thermal treatments showed similar patterns for most phenolic groups; an increase in proanthocyanidins, no change in ellagic acid conjugates, and a major decrease in flavonols and anthocyanins. In apples, mild treatments and high-pressure processing had similar effects in all phenolic groups, with increases in dihydrochalcones, hydroxycinnamics, and proanthocyanidins and decreases in flavonols. However, the standard thermal treatment increased flavonols and dihydrochalcones concentrations. This study shows that each fruit behaves differently, and both technology and processing conditions should be customized accordingly to preserve or even increase the phenolic content.

The objective of this study was to investigate the orexin and POMC populations in the hypothalamic nuclei of male Wistar rats after the activity-based anorexia (ABA) procedure. Four groups were established based on food restriction and activity: activity (A), ABA, diet (D) and control (C). The ABA protocol consisted of free access to a running wheel for a period of 22 h and access to food for 1 h. When the animals in the ABA group reached the ABA criterion, were sacrificed, and their brains were collected and serially sectioned. The free-floating sections were processed for orexin and POMC immunostaining. The number of orexin A-ir cells in the perifornical-dorsomedial-hypothalamus continuum (PFD) and lateral hypothalamus (LH) and the number of POMC-ir cells in the arcuate nucleus (Arc) were estimated. Data on food intake, body weight and wheel turns were also analyzed. The ABA procedure caused a significant decrease in body weight along with a significant increase in activity. Moreover, at the end of the ABA procedure, the number of POMC-ir cells decreased in the Arc in the A group, and significantly more in the ABA group, and the number of orexin A-ir positive cells decreased in the LH in D and ABA groups. The differential decrease in POMC in the ABA group emphasizes the importance of the melanocortin system in the maintenance of ABA, but more research is needed to elucidate the involvement of this peptide in the mechanism that promotes and maintains anorexia nervosa and how increased activity may interact with all these processes.

Ischemia has been a persistent and largely unavoidable element in solid organ transplantation, contributing to graft deterioration and adverse post-transplant outcomes. In liver transplantation, where available organs arise with greater frequency from marginal donors (i.e., ones that are older, obese, and/or declared dead following cardiac arrest through the donation after circulatory death process), there is increasing interest using dynamic perfusion strategies to limit, assess, and even reverse the adverse effects of ischemia in these grafts. Normothermic perfusion, in particular, is used to restore the flow of oxygen and other metabolic substrates at physiological temperatures. It may be used in liver transplantation both in situ following cardiac arrest in donation after circulatory death donors or during part or all of the ex situ preservation phase. This review article addresses issues relevant to use of normothermic perfusion strategies in liver transplantation, including technical and logistical aspects associated with establishing and maintaining normothermic perfusion in its different forms and clinical outcomes that have been reported to date.

PM2.5 that have been related to public health risks, were collected during two seasons with High-Vol samplers in platforms of a Mexican subway station, which interconnects through transfers three lines having different depths. The objective was to study the influence of depth on the PM2.5 concentrations and their species. PM2.5 concentrations in cold-dry and warm-dry seasons presented statistical differences, being in average 57 and 66 μgm−3 respectively, in the shallower line 9; 90 μgm−3 and 111 μgm−3 in line 1; and 104 and 122 μgm−3in the deepest line 7. During the cold-dry season and warm-dry season PM2.5concentrations in the subway environment were respectively up to 3.5 times and up to 5 times greater than in the ambient air. Like PM2.5, metals analyzed with an OES-ICP presented higher concentrations in deeper lines as well as PAHs quantified with CG-MS, which ranged from 4.5 to 11.7 ngm−3. High PM2.5, metals and organic toxic concentrations found in deeper lines of the subway environment represent a risk for commuters endorsing the need for ventilation systems to reduce them. Zn, Pb, V and Ni in subway particles presented the highest solubility in artificial lysosomal fluid suggesting high bioavailability in the lung fluids.

Clinical and epidemiological evidence supports that pregnancies carrying a male fetus are more vulnerable to infections and preterm birth, probably due to testosterone immunosuppressive properties. In human placentas, testosterone lowers the expression of CYP27B1, the vitamin D (VD)-activating enzyme, diminishing cathelicidin synthesis, a potent VD-dependent antimicrobial peptide (AMP). VD also stimulates other AMPs, including defensins. To get insights into the increased male vulnerability mechanisms, we investigated the relationship between fetal sex and the immunoendocrine milieu at the fetoplacental unit. For this, umbilical vein serum and placental samples were collected from healthy newborns. In males' serum, testosterone levels were significantly higher and negatively associated with TNF-α, a cytokine that strengthens the immune response. Males showed lower serum TNF-α and increased levels and gene expression of the immunosuppressive cytokine IL-10. Only in female samples there was a positive association (P 0.05) between AMPs and both TNF-α and CYP27B1 and between 25-hydroxyvitamin D

Medulloblastoma (MB) is the most common and aggressive pediatric intracranial tumor. Estrogen receptor β (ERβ) expression correlates with MB development and its phosphorylation modifies its transcriptional activity in a ligand-dependent or independent manner. Using in silico tools, we have identified several residues in ERβ protein as potential targets of protein kinases C (PKCs) α and δ. Using Daoy cells, we observed that PKCα and PKCδ associate with ERβ and induce its phosphorylation. The activation of ERβ promotes MB cells proliferation and invasion, and PKCs downregulation dysregulates these steroid receptor mediated processes. Our data suggest that these kinases may play a crucial role in the regulation of the ERβ transcriptional activity. Overexpression of both PKCα and PKCδ in MB biopsies samples supports their relevance in MB progression.

Background: Coronavirus Disease 2019 (COVID-19) pandemic has implacably stricken on the wellness of many countries and their health-care systems. The aim of the present study is analyze the clinical characteristics of the initial wave of patients with COVID-19 attended in our center, and to identify the key variables predicting the development of respiratory failure. Methods: We retrospectively recruited all hospitalized adult patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rRT-PCR assay performed on respiratory samples from March 2nd to 18th, 2020. Patients were followed up to May 1st, 2020 or death. Respiratory failure was defined as a PaO2/FiO2 ratio ≤200 mm Hg or the need for mechanical ventilation (either non-invasive positive pressure ventilation or invasive mechanical ventilation). Findings: We included 521 patients of whom 416 (81%) had abnormal Chest X-ray on admission. Median age was 64·6 ± 18·2 years, with 317 patients (60.8%) over 60 years. One hundred eighty-one (34·7%) developed respiratory failure after a median time from onset of symptoms of 9 days (IQR: 6-11) and the in-hospital mortality was 23·8% (124/521). The modelling process concluded into a logistic regression multivariable analysis and a predictive score at admission. Age, peripheral pulse oximetry, lymphocyte count, lactate dehydrogenase and C-reactive protein were the selected variables. The model has a good discriminative capacity with an area under the ROC curve of 0·85 (0·82-0·88). Interpretation: The application of a simple and reliable score at admission seems to be a useful tool to predict respiratory failure in hospitalized COVID-19 patients. Funding: This study was supported by the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (COVID-19 research call COV20/00181) — co‐ financed by the European Development Regional Fund “A way to achieve Europe”. Mikel Mancheno-Losa was supported by a Research Contract “Rio Hortega” from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (CM19/00226). Mario Fernandez-Ruiz holds a research contract “Miguel Servet” from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (CP 18/00073). Declaration of Interests: The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript. Ethics Approval Statement: The protocol was approved by the Hospital 12 de Octubre Clinical Research Ethics Committee (reference 20/117) and granted a waiver of informed consent due to its retrospective observational design.