To Mob or Not to Mob: Habitat and Time of Day Influence in Mobbing Behavior in the Azure-Winged Magpie (Cyanopica cookii).

While mobbing, individuals utter distinctive calls and perform visual threatening displays. Like any other antipredatory strategies, it involves some costs (time, energy, injuries, and even death). Therefore, mobbing would be expected to vary depending on the perceived magnitude of the predation risk. Moreover, harassment behavior can also serve as a demonstration of social status and to teach juveniles to recognize predators and related behaviors. Therefore, mobbing could also persist even when predation risk is particularly low. To test our hypotheses, we used tawny owl playbacks and a taxidermy mount to elicit the mobbing response in azure-winged magpies throughout the daylight period. To classify mobbing intensity, we created five categories depending on the proximity to the owl model at which the mobbing was performed. The results revealed that mobbing behavior in azure-winged magpies was more intense where predation risk was higher: in the most suitable habitat for the tawny owl, the forest, although considerable levels of mobbing were found in the dehesa and the ecotone, which indicate that mobbing has different purposes. However, we did not find statistically significant differences in mobbing intensity depending on the time of the day. We could not show a daily adjustment of antipredator response, but magpies modulated mobbing depending on the perceived risk linked to the habitat.

Colour Preferences in Relation to Diet in Chimpanzees(Pan troglodytes), Gorillas (Gorilla gorilla) and Mandrills (Mandrillus sphinx).

Although trichromatic colour vision has been extensively studied as it grants significant advantages for Old World primates, it is unknown which selective pressures were behind the trait's evolution. The leading hypothesis would be that colour vision arose as a foraging adaptation because it allowed individuals to spot food more efficiently. To test this, we exposed 3 chimpanzees (Pan troglodytes), 5 gorillas (Gorilla gorilla) and 3 mandrills (Mandrillus sphinx) to colour cardboard plates to assess whether colours related to diet were the most preferred. The experimental setting was divided into two phases. During the first, animals were provided with colour cardboard plates of only 1 colour per data collection session. The order of colour presentation was randomly determined: white, black, yellow, green and red. In phase 2, primates were simultaneously provided with cardboard plates of all colours. Behavioural interactions with plates were measured using a one-zero group focal sampling (10-s sampling intervals and 20-min observation periods). Results showed that when animals were exposed to only 1 colour at a time, they exhibited different colour preferences depending on the species considered. Chimpanzees preferred red and yellow, the colours linked to fruits, while gorillas selected red and white. Mandrills exhibited fewer differences between colour preferences, with red being the most selected. Furthermore, when all colours were simultaneously provided, individuals chose colours related to diet over black and white. Although there were clear individual differences, our results support that trichromatic colour vision is an advantage in detecting and selecting red items. In the wild, it could be important in the detection of reddish fruits and leaves.

Cardiomyogenic differentiation potential of human endothelial progenitor cells isolated from patients with myocardial infarction.

BACKGROUND AIMS: Endothelial progenitor cells (EPCs) are known to play a beneficial role by promoting postnatal vasculogenesis in pathological events, such as ischemic heart disease and peripheral artery disease. However, little is known about the potential of EPCs to restore heart damage tissue. We compared the cardiac differentiation capacity of EPCs isolated from peripheral blood of patients with acute myocardial infarction (AMI) with EPCs obtained from umbilical cord blood (UCB). METHODS: EPCs from both origins were isolated by density gradient centrifugation and characterized through the use of endothelial markers (UEA-1lectin, CD133 and KDR) and endothelial cell colony-forming unit assay. Cardiac differentiation capacity of EPCs was assessed by immunofluorescence and reverse transcriptase-polymerase chain reaction after 5-azacytidine (5-aza) induction. RESULTS: No significant differences were observed between the number of endothelial cell colony-forming units in peripheral blood of patients with AMI and samples from UCB. Moreover, 5-aza induced the appearance of myotube-like structures and the positive expression of sarcomeric α-actinin, cardiac troponin I and T and desmin in a similar pattern for both cell sources, which indicates a comparable acquisition of a cardiac-like phenotype. CONCLUSIONS: For the first time, we have compared, in vitro, the cardiomyogenic potential of EPCs derived from patients with AMI with UCB-derived EPCs. Our data indicate that EPCs obtained from both origins have similar plasticity and functions and suggest a potential therapeutic efficacy in cardiac cell therapy.

Onto the sense of smell in macaws, amazons and toucans: can they use volatile cues of fruits to make foraging decisions?

Over the past decades, empirical evidence has been accumulated indicating that olfactory information plays a fundamental role in bird life history. Nonetheless, many aspects of avian olfaction remain poorly understood. Our purpose was to broaden the knowledge about the importance of the sense of smell in some neglected bird groups: psittaciformes and ramphastids, and to compare how the response varied between the species. Because of the lack of information about the use of chemical cues for locating food in fruit-eating species, we also aimed to delve into this question. We conducted a 3-choice (water/vinegar/papaya and banana juice) scent test in 5 Costa Rican native species: scarlet macaw (Ara macao), red-lored amazon (Amazona autumnalis), yellow-naped amazon (Amazona auropalliata), keel-billed toucan (Ramphastos sulfuratus), and yellow-throated toucan (Ramphastos ambiguus). Results revealed that macaws and toucans allocated significantly more time to interacting with the fruit scent container, indicating that these species can perceive the volatile chemicals emitted by ripe fruits and that they can use this information to make foraging decisions. However, amazons did not dedicate more time to interact with the fruit treatment. Our research provides the first evidence of the ability to exploit chemical volatile cues in macaws and toucans.

An Experimental Study in Wild Wood Mice Testing Elemental and Isotope Analysis in Faeces to Determine Variations in Food Intake Amount.

The analysis of carbon and nitrogen elemental (C, N) and isotopic compositions (δ13C, δ15N) in faeces are considered reliable methodologies for the study of diet in wildlife. Here, we tested the suitability of these techniques to detect variations in the amount of food intake. We captured wild wood mice (Apodemus sylvaticus) with Sherman live traps where bait access was initially free, and later it was experimentally limited inside by four different devices to cause intended variations in the amount ingested. The total C and N (%) and stable δ13C and δ15N isotopic values were determined for the bait and in mice faecal samples. Faecal values were lower than bait ones except for N, likely due to animal matter ingested before capture. No significant differences in total C, N and δ13C were found due to individual traits. However, breeding males showed higher δ15N values than breeding females, probably due to differences in energy and protein demands between both sexes during the breeding season. Only δ13C detected food intake variations (≥2 g). Despite further research being needed, these results initially support the potential of δ13C to provide information on the amount ingested, thus being useful to complement trophic ecology studies.

PI3Kß-regulated ß-catenin mediates EZH2 removal from promoters controlling primed human ESC stemness and primitive streak gene expression.

The mechanism governing the transition of human embryonic stem cells (hESCs) toward differentiated cells is only partially understood. To explore this transition, the activity and expression of the ubiquitous phosphatidylinositol 3-kinase (PI3Kα and PI3Kß) were modulated in primed hESCs. The study reports a pathway that dismantles the restraint imposed by the EZH2 polycomb repressor on an essential stemness gene, NODAL, and on transcription factors required to trigger primitive streak formation. The primitive streak is the site where gastrulation begins to give rise to the three embryonic cell layers from which all human tissues derive. The pathway involves a PI3Kß non-catalytic action that controls nuclear/active RAC1 levels, activation of JNK (Jun N-terminal kinase) and nuclear ß-catenin accumulation. ß-Catenin deposition at promoters triggers release of the EZH2 repressor, permitting stemness maintenance (through control of NODAL) and correct differentiation by allowing primitive streak master gene expression. PI3Kß epigenetic control of EZH2/ß-catenin might be modulated to direct stem cell differentiation.

Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells.

BACKGROUND: In obstructive congenital hydrocephalus, cerebrospinal fluid accumulation is associated with high intracranial pressure and the presence of periventricular edema, ischemia/hypoxia, damage of the white matter, and glial reactions in the neocortex. The viability and short time effects of a therapy based on bone marrow-derived mesenchymal stem cells (BM-MSC) have been evaluated in such pathological conditions in the hyh mouse model. METHODS: BM-MSC obtained from mice expressing fluorescent mRFP1 protein were injected into the lateral ventricle of hydrocephalic hyh mice at the moment they present a very severe form of the disease. The effect of transplantation in the neocortex was compared with hydrocephalic hyh mice injected with the vehicle and non-hydrocephalic littermates. Neural cell populations and the possibility of transdifferentiation were analyzed. The possibility of a tissue recovering was investigated using 1H High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance (1H HR-MAS NMR) spectroscopy, thus allowing the detection of metabolites/osmolytes related with hydrocephalus severity and outcome in the neocortex. An in vitro assay to simulate the periventricular astrocyte reaction conditions was performed using BM-MSC under high TNFα level condition. The secretome in the culture medium was analyzed in this assay. RESULTS: Four days after transplantation, BM-MSC were found undifferentiated and scattered into the astrocyte reaction present in the damaged neocortex white matter. Tissue rejection to the integrated BM-MSC was not detected 4 days after transplantation. Hyh mice transplanted with BM-MSC showed a reduction in the apoptosis in the periventricular neocortex walls, suggesting a neuroprotector effect of the BM-MSC in these conditions. A decrease in the levels of metabolites/osmolytes in the neocortex, such as taurine and neuroexcytotoxic glutamate, also indicated a tissue recovering. Under high TNFα level condition in vitro, BM-MSC showed an upregulation of cytokine and protein secretion that may explain homing, immunomodulation, and vascular permeability, and therefore the tissue recovering. CONCLUSIONS: BM-MSC treatment in severe congenital hydrocephalus is viable and leads to the recovery of the severe neurodegenerative conditions in the neocortex. NMR spectroscopy allows to follow-up the effects of stem cell therapy in hydrocephalus.

In Vivo 1H Magnetic Resonance Spectroscopy.

In vivo Magnetic Resonance Spectroscopy (MRS) allows the non-invasive detection and quantification of a number of metabolites from localized volumes within a living organism. MRS localization techniques can be divided into two main groups, single voxel and multi-voxel. Single voxel techniques provide the metabolic profile from a specific small volume, whereas multi-voxel techniques are used to obtain the spatial distribution of metabolites throughout a large volume subdivided into small contiguous voxels. This chapter describes standard protocols for the acquisition and processing of in vivo single voxel1H MRS data from the rodent brain.

A Distinct Metabolite Profile Correlates with Neurodegenerative Conditions and the Severity of Congenital Hydrocephalus.

In congenital hydrocephalus, cerebrospinal fluid accumulation is associated with increased intracranial pressure (ICP), ischemia/hypoxia, metabolic impairment, neuronal damage, and astrocytic reaction. The aim of this study was to identify whether a metabolite profile revealing tissue responses according to the severity of hydrocephalus can be detected. The hyh mutant mouse used for this study exhibits 2 different forms of hydrocephalus, severe and moderate. In a comprehensive investigation into the 2 progressions of hydrocephalus, mice with severe hydrocephalus were found to have higher ICP and astrocytic reaction. Several metabolites from the mouse brain cortex were analyzed with 1H high-resolution magic angle spinning nuclear magnetic resonance (1H HR-MAS NMR) spectroscopy. A differential profile for metabolites including glutamate and glutamine was found to correlate with the severity of hydrocephalus and can be explained due to differential astrocytic reactions, neurodegenerative conditions, and the presence of ischemia. The glutamate transporter EAAT2 and the metabolite taurine were found to be key histopathological markers of affected parenchymata. In conclusion, a differential metabolite profile can be detected according to the severity of hydrocephalus and associated ICP and therefore can be used to monitor the efficacy of experimental therapies.

A label-free nanostructured plasmonic biosensor based on Blu-ray discs with integrated microfluidics for sensitive biodetection.

Nanostructure-based plasmonic biosensors have quickly positioned themselves as interesting candidates for the design of portable optical biosensor platforms considering the potential benefits they can offer in integration, miniaturization, multiplexing, and real-time label-free detection. We have developed a simple integrated nanoplasmonic sensor taking advantage of the periodic nanostructured array of commercial Blu-ray discs. Sensors with two gold film thicknesses (50 and 100nm) were fabricated and optically characterized by varying the oblique-angle of the incident light in optical reflectance measurements. Contrary to the use normal light incidence previously reported with other optical discs, we observed an enhancement in sensitivity and a narrowing of the resonant linewidths as the light incidence angle was increased, which could be related to the generation of Fano resonant modes. The new sensors achieve a figure of merit (FOM) up to 35 RIU-1 and a competitive bulk limit of detection (LOD) of 6.3×10-6 RIU. These values significantly improve previously reported results obtained with normal light incidence reflectance measurements using similar structures. The sensor has been combined with versatile, simple, ease to-fabricate microfluidics. The integrated chip is only 1cm2 (including a PDMS flow cell with a 50µm height microfluidic channel fabricated with double-sided adhesive tape) and all the optical components are mounted on a 10cm×10cm portable prototype, illustrating its facile miniaturization, integration and potential portability. Finally, to assess the label-free biosensing capability of the new sensor, we have evaluated the presence of specific antibodies against the GTF2b protein, a tumor-associate antigen (TAA) related to colorectal cancer. We have achieved a LOD in the pM order and have assessed the feasibility of directly measuring biological samples such as human serum.

Radiobiology of radioimmunotherapy with 90Y ibritumomab tiuxetan (Zevalin).

Radioimmunotherapy represents a significant advance over unlabeled immunotherapy for the treatment of patients with B-cell non-Hodgkin's lymphoma. The efficacy of radioimmunotherapeutic agents depends in large part on the basic biological effects associated with their components, monoclonal antibodies and radionuclides, separately and in combination. The radiobiological effects associated with yttrium 90-labeled ibritumomab tiuxetan (Zevalin; Biogen Idec Inc, Cambridge, MA) include the induction of apoptosis and cell-cycle redistribution (eg, arrest of cells in the G(2)/M phase of the cell cycle). Because of dose-rate effects, tumor cells may, in some cases, be more susceptible to the low-dose-rate radiation used in radioimmunotherapy than to the high-dose-rate radiation used in external beam radiotherapy. The efficacy of radioimmunotherapy may potentially be optimized through a variety of approaches, including the use of agents that increase the expression of certain tumor antigens (thus facilitating improved biodistribution of radiolabeled monoclonal antibodies) or that sensitize tumor cells to radiation.

Radiobiology of radioimmunotherapy: targeting CD20 B-cell antigen in non-Hodgkin's lymphoma.

The radiobiology of radioimmunotherapy is an important determinant of both the toxicity and the efficacy associated with the treatment of B-cell non-Hodgkin's lymphoma with radiolabeled anti-CD20 monoclonal antibodies. The properties of the target, CD20, and the mechanisms of action of both the monoclonal antibodies and the associated exponentially decreasing low-dose-rate radiotherapy are described. The radiation dose and dose-rate effects are discussed and related to both the tumor responses and normal organ toxicity. Finally, the use of either unlabeled or radiolabeled anti-CD20 monoclonal antibodies as a component of combined modality therapy (including the sequential or concurrent use of sensitizers) and future directions of the field are discussed.

Review of the novelties presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (III).

The most relevant data presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in October 2013 in Denmark, were summarised at the sixth edition of the Post-ECTRIMS Expert Meeting held in Madrid in October 2013, resulting in this review, which is being published in three parts. This third part of the Post-ECTRIMS review discusses the effects of immunomodulatory therapy on the natural history of multiple sclerosis, with special attention to the assessment of long-term effects and the use of historical controls as an alternative to randomised trials compared with placebo. This article contains possible future therapeutic strategies to be tested in experimental models and discusses clinical trials that are underway and future treatments. It also summarises the results of recent studies of disease-modifying treatments and developments in symptom management. Briefly, on the horizon are many drugs with different mechanisms of action, although new strategies and treatment algorithms are needed, as are new biomarkers and assessment measures of secondary progression and long-term records to assess safety. As for the symptomatic treatment of the disease, the proposal is a personalised treatment plan and a multidisciplinary approach to improve the quality of life of patients.

TITLE: Revision de las novedades presentadas en el XXIX Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS) (III).Los datos mas relevantes presentados en la XXIX edicion del Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS), celebrado en octubre de 2013 en Dinamarca, se han resumido en la sexta edicion de la Reunion de Expertos Post-ECTRIMS celebrada en Madrid en octubre de 2013, fruto de la cual nace esta revision, que se publica en tres partes. Esta tercera parte de la revision Post-ECTRIMS aborda los efectos del tratamiento inmunomodulador en la historia natural de la esclerosis multiple, con especial atencion a la valoracion del efecto a largo plazo y al uso de controles historicos como alternativa a los estudios aleatorizados comparados con placebo. Este articulo recoge posibles estrategias terapeuticas futuras que pasan por los modelos experimentales, y expone los ensayos clinicos en marcha y futuros tratamientos. Asimismo, resume los resultados de los ultimos estudios de los tratamientos modificadores de la enfermedad y las novedades en el manejo sintomatico. Brevemente, en el horizonte, hay muchos farmacos con diferentes mecanismos de accion, aunque son necesarias nuevas estrategias y algoritmos terapeuticos, biomarcadores y nuevas medidas de evaluacion de la progresion secundaria, y registros a largo plazo para evaluar la seguridad. En cuanto al tratamiento sintomatico de la enfermedad, se apuesta por un plan personalizado de tratamiento y una aproximacion multidisciplinar, de cara a mejorar la calidad de vida de los pacientes.

[Review of the novelties presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (II)].

The most relevant data presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in October 2013 in Denmark, were summarised at the sixth edition of the Post-ECTRIMS Expert Meeting, held in Madrid in October 2013, resulting in this review, which is being published in three parts. This second part of the Post-ECTRIMS review focuses on diagnostic imaging and differential diagnosis, the clinical and paraclinical monitoring of neurodegeneration, progression and disability, and functional imaging and neural connectivity. It is clear that conventional multiple sclerosis sequences remain essential for the diagnosis, differential diagnosis and disease monitoring, that new MRI techniques help to assess the neurodegenerative process, and that some of the new sequences are more specific to neuroaxonal injury. Very high field magnetic resonance imaging allows better understanding of the lesion load, distribution and heterogeneity of the lesions, and positron emission tomography studies offer new insight into the patho-physiology of the disease. Functional imaging and neural connectivity studies show that there is cortical reorganisation in multiple sclerosis, whose equilibrium with structural damage is responsible for the impairment.

TITLE: Revision de las novedades presentadas en el XXIX Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS) (II).Los datos mas relevantes presentados en la XXIX edicion del Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS), celebrado en octubre de 2013 en Dinamarca, se han resumido en la sexta edicion de la Reunion de Expertos Post-ECTRIMS celebrada en Madrid en octubre de 2013, fruto de la cual nace esta revision, que se publica en tres partes. Esta segunda parte de la revision Post-ECTRIMS se centra en la imagen del diagnostico y diagnostico diferencial, en la monitorizacion clinica y paraclinica de la neurodegeneracion, progresion y discapacidad, y en la imagen funcional y conectividad neural. Queda patente que las secuencias convencionales de esclerosis multiple siguen siendo basicas para el diagnostico, el diagnostico diferencial y el seguimiento de la enfermedad, que las nuevas tecnicas de resonancia magnetica ayudan a evaluar el proceso de neurodegeneracion, y algunas de las nuevas secuencias son mas especificas del daño neuronal-axonal. La resonancia magnetica de campo muy alto permite un mejor conocimiento de la carga lesional, distribucion y heterogeneidad de las lesiones, y los estudios con tomografia por emision de positrones ofrecen una nueva vision de la fisiopatologia de la enfermedad. Los estudios de imagen funcional y conectividad neural muestran que en la esclerosis multiple existe una reorganizacion cortical cuyo equilibrio con el daño estructural es responsable de la discapacidad.

Review of the novelties presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (III).

The most significant data presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in France in October 2012, have been summarised in the fifth edition of the Post-ECTRIMS Experts Meeting, held in Madrid in October 2012. This led to the drafting of this review, which has been published in three parts. This third part of the Post-ECTRIMS review presents the findings from the latest studies conducted with disease-modifying treatments, more specifically with glatiramer acetate, laquinimod, ponesimod, BG-12, teriflunomide, daclizumab, natalizumab and secukinumab (AIN457). Likewise, we also address the reasons that justify the search for innovative treatments for multiple sclerosis, with antigen-specific therapy, cell therapy and therapy aimed at promoting remyelination being highlighted among other future therapeutic strategies. Access to new pharmacological agents and the complexity of the therapy of multiple sclerosis in the future will require new design strategies and directions in clinical trials, including the use of surrogate markers, new statistical applications, superiority, inferiority or equivalence clinical trials and adaptable designs.

TITLE: Revision de las novedades presentadas en el XXVIII Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS) (III).Los datos mas relevantes presentados en la XXVIII edicion del Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS), celebrado en octubre de 2012 en Francia, han sido resumidos en la quinta edicion de la Reunion de Expertos Post-ECTRIMS celebrada en Madrid en octubre de 2012, fruto de la cual nace esta revision que se publica en tres partes. Esta tercera parte de la revision Post-ECTRIMS expone los resultados de los ultimos estudios realizados con los tratamientos modificadores de la enfermedad, concretamente con acetato de glatiramero, laquinimod, ponesimod, BG-12, teriflunomida, daclizumab, natalizumab y secukinumab (AIN457). Asimismo, se abordan las razones que justifican la busqueda de tratamientos innovadores para la esclerosis multiple, destacando la terapia antigenoespecifica, la terapia celular y la terapia dirigida a promover la remielinizacion entre las futuras estrategias terapeuticas. La disponibilidad de nuevos farmacos y la complejidad de la futura terapia de la esclerosis multiple necesitan nuevas direcciones y estrategias de diseño en los ensayos clinicos, entre ellas el uso de marcadores subrogados, nuevas aplicaciones estadisticas, ensayos clinicos de superioridad, inferioridad o equivalencia, y diseños adaptables.

Review of the novelties presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (I).

The most relevant data presented at the 28th edition of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in October 2012 in France, have been summarized in the fifth edition of the Post-ECTRIMS Expert Meeting held in Madrid in October 2012. The present review summarizes the views and results of the meeting and is being published in three parts. This first part of the Post-ECTRIMS review addresses the incidence and prevalence of multiple sclerosis (MS), which has increased at the global level, largely due to the increased incidence in women because the risk of developing the disease is increased in females, with minimal concurrent effect on the progression of MS. Sexual dimorphism is evident in MS, and all evidence points to an interaction between hormonal, genetic, and environmental factors. The paediatric population represents an ideal group to study susceptibility factors to the disease, which is why collaborative studies designed to increase the patient samples are being considered, given its low prevalence. In this review, inflammatory and neurodegenerative phenomena involved in the pathogenesis of the disease and that have a cause-and-effect or shared relationship with the disease are being discussed. Current hypotheses suggest a phenomenon of compartmentalization, presumably inaccessible to current immunomodulatory therapy. Among the possible mechanisms involved in these processes of inflammation and demyelination, the role of Th17 cells, mitochondrial dysfunction, early disruption of astrocytic processes, and chronic hypoxia are discussed.

TITLE: Revision de las novedades presentadas en el XXVIII Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS) (I).Los datos mas relevantes presentados en la XXVIII edicion del Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS), celebrado en octubre de 2012 en Francia, se han resumido en la quinta edicion de la Reunion de Expertos Post-ECTRIMS celebrada en Madrid en octubre de 2012, fruto de la cual nace esta revision, que se publica en tres partes. Esta primera parte de la revision Post-ECTRIMS aborda la incidencia y prevalencia de la esclerosis multiple (EM), que, en el ambito mundial, ha aumentado a expensas de las mujeres, ya que el sexo femenino aumenta el riesgo de desarrollar la enfermedad, aunque no afecta de forma negativa a su evolucion. El dimorfismo sexual en la EM es evidente, y todo apunta a una interaccion entre factores hormonales, geneticos y medioambientales. La poblacion pediatrica representa un grupo idoneo para el estudio de factores de susceptibilidad a la enfermedad, razon por la que se estan planteando estudios colaborativos ideados para aumentar la muestra de pacientes, dada su baja prevalencia. En esta revision se discute sobre los fenomenos inflamatorios y de neurodegeneracion que intervienen en la patogenia de la enfermedad, y que probablemente esten relacionados, bien de forma compartida o como causa efecto. Las hipotesis actuales apuntan a un fenomeno de compartimentacion presumiblemente inaccesible a la terapia inmunomoduladora actual. Entre los posibles mecanismos involucrados en estos procesos de inflamacion y desmielinizacion se discute el papel de las celulas Th17, disfuncion mitocondrial, disrupcion precoz de procesos astrocitarios e hipoxia cronica.

Review of the novelties presented at the 27th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (II).

The new insights presented at the 5th Joint Triennial Congress of the European and Americas Committees on Treatment and Research in Multiple Sclerosis (ECTRIMS and ACTRIMS) held in Amsterdam, the Netherlands, 19-22 October 2011, have been summarized at the fourth edition of Post-ECTRIMS meeting held in Madrid in November 2011. Regional grey-matter atrophy is more sensitive to cognitive impairment than global grey-matter atrophy measures. In patients with clinically isolated syndrome cognitive impairment does not predict conversion to multiple sclerosis (MS) after 5-years of follow-up. Focusing on central nervous system plasticity and functional reorganization in MS, an early intervention can improve clinical aspects and enhances brain plasticity. Preservation of a potential for plasticity provides a rationale for rehabilitation interventions even in later stages of disease. Therapeutical strategies have focused on stem cell-mediated remyelination and immunomodulation functions, on cellular infiltration into the brain, and on new ways for immuno-modulation for the development of future therapies in MS. Encouraging findings from clinical trials with current and emerging disease-modifying therapy being developed was also a key theme at this edition. Positive results have been reported for rituximab, ocrelizumab, ofatumumab, daclizumab, alemtuzumab, teriflunomide, BG-12, and laquinimod, including a favorable safety profile. Since armamentarium for the treatment of MS is fast increasing, concerns exist about the risk of severe adverse events with their use. This aspect reinforces the importance of disease registries as a proactive tool for monitoring drug safety in the post-approval setting.

Review of the novelties presented at the 27th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (I).

The new insights presented at the 5th Joint Triennial Congress of the European and Americas Committees on Treatment and Research in Multiple Sclerosis (ECTRIMS and ACTRIMS) held in Amsterdam, the Netherlands, 19-22 October 2011, have been summarized at the fourth edition of Post-ECTRIMS meeting held in Madrid in November 2011. Further evidence from epidemiological studies yield a possible relationship between nutrition and alterations of the microbiota that may result in the development of multiple sclerosis (MS) and that may trigger the exacerbation of disease symptoms. Also show the magnitude of impact of comorbidities in multiple sclerosis course as well as the impact of early identification and management. Review of current data on chronic cerebrospinal venous insufficiency and MS sclerosis concludes that there is no role of chronic cerebrospinal venous insufficiency in either multiple sclerosis risk or MS severity. New diagnostic criteria for MS have simplified requirements for demonstrating dissemination of lesions in time. High-field magnetic resonance imaging improves cortical visualization and become a promising tool to detect remyelinization and cortical and medullary lesions, and optical coherence tomography is established as a powerful tool for neuroprotection trials. Diffuse meningeal inflammation through B-cell follicle-like structures is associated with cortical pathology and an accelerated clinical course in secondary progressive MS sclerosis. Systemic inflammation may contribute to neurodegeneration processes in MS, and with regard to grey matter damage recent findings conclude that occurs early in disease course, and correlates with future MS-related disability.

[Review of the novelties presented at the 26th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (I)]. / Revision de las novedades presentadas en el XXVI Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS) (I).

The new insights presented at European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in the city of Gothenburg, Sweden, in October 2010, have been summarized at the third edition of Post-ECTRIMS meeting held in Madrid in November 2010. The age is an important factor related to the course and prognosis of multiple sclerosis (MS). The evolution to progressive disease persists more than 50 years after diagnosis of MS and a reduction in the delay of diagnosis has been detected. Several strategies have been proposed in order to improve the efficacy of magnetic resonance regarding prognosis and course of disease. The studies presented at the Congress reflect the influence of gender on course and severity of disease symptoms, showing an increase of worldwide prevalence of MS in women. Neuroprotective action of estrogen receptor beta has been reported. The genome wide association studies have allowed investigators to identify numerous susceptible alleles. In this regard, HLA class II genes, seems to contribute to genetic risk for developing neutralizing antibodies against beta-interferon. Vitamin D deficiency and Epstein-Barr virus have been highlighted as risk factors for MS in the reported findings. On the subject of the ongoing controversy regarding the role of inflammation and degeneration in MS, several arguments have been found to support the role of CNS autoimmunity to explain the presence of inflammatory phenomenon. The available data hold the potential therapeutic role of mesenchymal cells given the involvement of these stem cells in CNS repair.