Metabolic gene expression changes in astrocytes in Multiple Sclerosis cerebral cortex are indicative of immune-mediated signaling.

Emerging as an important correlate of neurological dysfunction in Multiple Sclerosis (MS), extended focal and diffuse gray matter abnormalities have been found and linked to clinical manifestations such as seizures, fatigue and cognitive dysfunction. To investigate possible underlying mechanisms we analyzed the molecular alterations in histopathological normal appearing cortical gray matter (NAGM) in MS. By performing a differential gene expression analysis of NAGM of control and MS cases we identified reduced transcription of astrocyte specific genes involved in the astrocyte-neuron lactate shuttle (ANLS) and the glutamate-glutamine cycle (GGC). Additional quantitative immunohistochemical analysis demonstrating a CX43 loss in MS NAGM confirmed a crucial involvement of astrocytes and emphasizes their importance in MS pathogenesis. Concurrently, a Toll-like/IL-1β signaling expression signature was detected in MS NAGM, indicating that immune-related signaling might be responsible for the downregulation of ANLS and GGC gene expression in MS NAGM. Indeed, challenging astrocytes with immune stimuli such as IL-1β and LPS reduced their ANLS and GGC gene expression in vitro. The detected upregulation of IL1B in MS NAGM suggests inflammasome priming. For this reason, astrocyte cultures were treated with ATP and ATP/LPS as for inflammasome activation. This treatment led to a reduction of ANLS and GGC gene expression in a comparable manner. To investigate potential sources for ANLS and GGC downregulation in MS NAGM, we first performed an adjuvant-driven stimulation of the peripheral immune system in C57Bl/6 mice in vivo. This led to similar gene expression changes in spinal cord demonstrating that peripheral immune signals might be one source for astrocytic gene expression changes in the brain. IL1B upregulation in MS NAGM itself points to a possible endogenous signaling process leading to ANLS and GGC downregulation. This is supported by our findings that, among others, MS NAGM astrocytes express inflammasome components and that astrocytes are capable to release Il-1β in-vitro. Altogether, our data suggests that immune signaling of immune- and/or central nervous system origin drives alterations in astrocytic ANLS and GGC gene regulation in the MS NAGM. Such a mechanism might underlie cortical brain dysfunctions frequently encountered in MS patients.

Atypical language organization in temporal lobe epilepsy revealed by a passive semantic paradigm

Background Mesial temporal lobe epilepsy (MTLE) is the most common type of focal epilepsy in adults and can be successfully cured by surgery. One of the main complications of this surgery however is a decline in language abilities. The magnitude of this decline is related to the degree of language lateralization to the left hemisphere. Most fMRI paradigms used to determine language dominance in epileptic populations have used active language tasks. Sometimes, these paradigms are too complex and may result in patient underperformance. Only a few studies have used purely passive tasks, such as listening to standard speech. Methods In the present study we characterized language lateralization in patients with MTLE using a rapid and passive semantic language task. We used functional magnetic resonance imaging (fMRI) to study 23 patients [12 with Left (LMTLE), 11 with Right mesial temporal lobe epilepsy (RMTLE)] and 19 healthy right-handed controls using a 6 minute long semantic task in which subjects passively listened to groups of sentences (SEN) and pseudo sentences (PSEN). A lateralization index (LI) was computed using a priori regions of interest of the temporal lobe. Results The LI for the significant contrasts produced activations for all participants in both temporal lobes. 81.8% of RMTLE patients and 79% of healthy individuals had a bilateral language representation for this particular task. However, 50% of LMTLE patients presented an atypical right hemispheric dominance in the LI. More importantly, the degree of right lateralization in LMTLE patients was correlated with the age of epilepsy onset. Conclusions The simple, rapid, non-collaboration dependent, passive task described in this study, produces a robust activation in the temporal lobe in both patients and controls and is capable of illustrating a pattern of atypical language organization for LMTLE patients. Furthermore, we observed that the atypical right-lateralization patterns in LMTLE patients was associated to earlier age at epilepsy onset. These results are in line with the idea that early onset of epileptic activity is associated to larger neuroplastic changes.

Juegos digitales en el aula: un caso de estudio

Durante el año 2011 se diseño, implementó y estudió un juego digital que muestra la vida de un científico Catalán: El paleontólogo Miquel Crusafont. El juego fue creado como un recurso para el aprendizaje cognitivo y posteriormente fue utilizado en aulas de primaria con el fin de obtener la visión de los profesores involucrados. Como método de recolección de datos se ha utilizado la observación, la entrevista en profundidad y el grupo focal. El objetivo principal de este estudio se centra en reunir la visión de profesores de primaria, al hacer uso de juegos en el aula. Las conclusiones nos muestran las percepciones que los miembros del grupo de estudio tiene sobre el uso de juegos digitales.

Acute stroke chameleons in a university hospital : Risk factors, circumstances, and outcomes.

OBJECTIVE: To identify risk factors, circumstances, and outcomes for individuals with acute ischemic stroke (AIS) chameleons (AIS-C) arriving in the emergency department of a university hospital. METHODS: We retrospectively reviewed all patients with AIS from the prospectively constructed Acute Stroke Registry and Analysis of Lausanne during 8.25 years. AIS-C were defined as a failure to suspect stroke or as incorrect exclusion of stroke diagnosis. They were compared with patients diagnosed correctly at the time of admission. RESULTS: Forty-seven of 2,200 AIS were missed (2.1%). These AIS-C were either very mild or very severe strokes. Multivariate analysis showed a younger age in patients with AIS-C (odds ratio [OR] per year 0.98, p < 0.01), less prestroke statin treatment (OR 0.29, p = 0.04), and lower diastolic admission blood pressure (OR 0.98 p = 0.04). They showed less eye deviation (OR 0.21, p = 0.04) and more cerebellar strokes (OR 3.78, p < 0.01). AIS-C were misdiagnosed as other neurologic (42.6% of cases) or nonneurologic (17.0%) disease, as unexplained decreased level of consciousness (21.3%), and as concomitantly present disease (19.1%). At 12 months, patients with AIS-C had less favorable outcomes (adjusted OR 0.21, p < 0.01) and higher mortality (adjusted OR 4.37, p < 0.01). CONCLUSIONS: AIS are missed in patients with younger age with a lower cerebrovascular risk profile and may be masked by other acute conditions. Patients with chameleons present more often with milder strokes or coma, fewer focal signs and cerebellar strokes, and have higher disability and mortality rates at 12 months. These findings may be used to raise awareness in emergency departments to recognize and treat such patients appropriately.

Uncovering Cryptic Parasitoid Diversity in Horismenus (Chalcidoidea, Eulophidae).

Horismenus parasitoids are an abundant and understudied group of eulophid wasps found mainly in the New World. Recent surveys based on morphological analyses in Costa Rica have quadrupled the number of named taxa, with more than 400 species described so far. This recent revision suggests that there is still a vast number of unknown species to be identified. As Horismenus wasps have been widely described as parasitoids of insect pests associated with crop plants, it is of high importance to properly establish the extant diversity of the genus, in order to provide biological control practitioners with an exhaustive catalog of putative control agents. In this study, we first collected Horismenus wasps from wild Phaseolus bean seeds in Central Mexico and Arizona to assess the genetic relatedness of three morphologically distinct species with overlapping host and geographical ranges. Sequence data from two nuclear and two mitochondrial gene regions uncovered three cryptic species within each of the three focal species (i.e., H. missouriensis, H. depressus and H. butcheri). The monophyly of each cryptic group is statistically supported (except in two of them represented by one single tip in which monophyly cannot be tested). The phylogenetic reconstruction is discussed with respect to differences between gene regions as well as likely reasons for the differences in variability between species.

Pneumocistose na síndrome da imunodeficiência adquirida: correlação da tomografia computadorizada de alta resolução com a anatomopatologia

Neste trabalho são apresentados os principais aspectos observados na tomografia computadorizada de alta resolução de 15 pacientes com a síndrome da imunodeficiência adquirida e pneumocistose, e feita a correlação com os achados da necropsia de cinco destes pacientes. Os padrões tomográficos mais freqüentemente observados foram a atenuação em vidro fosco, as áreas de consolidação, o padrão de pavimentação em mosaico e os cistos. Menos comumente foram identificados nódulos e reticulação intralobular. O padrão em vidro fosco e as áreas de consolidação corresponderam à ocupação alveolar por exsudato inflamatório. O espessamento dos septos interlobulares se deveu à infiltração celular e ao edema. No paciente com reticulação intralobular foi observado espessamento dos septos alveolares por infiltração celular e por fibrose. Os nódulos, observados em um dos pacientes, corresponderam a um acúmulo focal de microorganismos e células inflamatórias, com um padrão "granulomatoso".

Osakeyhtiön hallituksen jäsenen vastuu oikeustapausten valossa

Tutkielman kohteena on osakeyhtiön hallituksen jäsenen vastuu osakeyhtiön yhtiöoikeudellisena toimielimenä ja vastuun toteutuminen käytännössä korkeimman oikeuden ratkaisujen valossa. Tutkielman tarkoituksena on hallituksen koostumuksen, tehtävien ja toiminnan kautta selvittää, miten hallituksen eri jäsenten vastuu muodostuu. Tutkielmassa pyritään selventämään osakeyhtiön hallituksen toiminnan keskeisiä vastuualueita tutkielman aineiston perusteella. Tutkielman metodina on oikeustapausten analyysi ja sitä kautta lain oikean tulkinnan hakeminen. Tässä suhteessa tutkielma on oikeusdogmaattinen tulkintatutkimus. Tutkielma osoitti, että osakeyhtiön hallituksen jäsenyyteen liittyy paitsi vastuu tehtävien hoitamisesta, myös huomattava vahingonkorvausvastuu . Vastuu voi käytännössä kohdistua paitsi yhtiöön myös osakkeenomistajaan ja erityisesti yhtiön velkojaan. Tutkielma osoitti myös, että osakeyhtiön hallituksen jäseneksi aikovan on oltava selvillä tehtävään liittyvästä oikeudellisesta vastuusta. Tehtävää ei pidä ottaa vastaan, ellei omaa tehtävän huolellisen hoitamisen vaatimaa riittävää asiantuntemusta ja ammattitaitoa.

Type 1 diabetes mellitus in people with pharmacoresistant epilepsy: Prevalence and clinical characteristics.

BACKGROUND: There have been inconsistent reports on the potential association between diabetes mellitus and epilepsy. METHODS: We examined a consecutive cohort of 2016 people with pharmacoresistant epilepsy admitted to a tertiary medical centre. RESULTS: We identified 20 individuals with type 1 diabetes mellitus (T1DM); a point prevalence of 9.9 (95% CI: 6.4, 15.3) cases per 1000 individuals. This represents a more than two-fold increase relative to published prevalence estimates of T1DM in the general population. The onset of T1DM preceded that of epilepsy in 80% of individuals, by a median of 1.5 years. Individuals with T1DM were significantly more likely to have cryptogenic/unknown epilepsy relative to those with type 2 diabetes mellitus or without diabetes (85% versus 35% and 49%, p=0.045). All individuals with T1DM had focal epilepsy, the majority of which were temporal lobe in origin, although there was no evidence that this proportion was any different from those without T1DM (p>0.999). CONCLUSIONS: The prevalence of T1DM appears to be increased in people with pharmacoresistant epilepsy and is associated with cryptogenic/unknown epilepsy. These findings may have pathophysiological implications, especially in the context of anti-glutamic acid decarboxylase antibodies.

Ultra-high-resolution 3D imaging of atherosclerosis in mice with synchrotron differential phase contrast: a proof of concept study.

The goal of this study was to investigate the performance of 3D synchrotron differential phase contrast (DPC) imaging for the visualization of both macroscopic and microscopic aspects of atherosclerosis in the mouse vasculature ex vivo. The hearts and aortas of 2 atherosclerotic and 2 wild-type control mice were scanned with DPC imaging with an isotropic resolution of 15 μm. The coronary artery vessel walls were segmented in the DPC datasets to assess their thickness, and histological staining was performed at the level of atherosclerotic plaques. The DPC imaging allowed for the visualization of complex structures such as the coronary arteries and their branches, the thin fibrous cap of atherosclerotic plaques as well as the chordae tendineae. The coronary vessel wall thickness ranged from 37.4 ± 5.6 μm in proximal coronary arteries to 13.6 ± 3.3 μm in distal branches. No consistent differences in coronary vessel wall thickness were detected between the wild-type and atherosclerotic hearts in this proof-of-concept study, although the standard deviation in the atherosclerotic mice was higher in most segments, consistent with the observation of occasional focal vessel wall thickening. Overall, DPC imaging of the cardiovascular system of the mice allowed for a simultaneous detailed 3D morphological assessment of both large structures and microscopic details.

Los Grandes olvidados: las personas mayores en el entorno rural = The Great Forgotten Issue: Older People in Rural Context

Ageing is a heterogeneous subject being been able to distinguish profiles in function of sex, age, economic situation, cultural levels, habitat, family structure, health, etc. The objectives of this article are to identify forms of life to age in the rural environment and to concretize intervention proposals to increase active and participatory ways of life. 7 in-depth interviews to experts, 21 to older people, 5 to professionals and two focal groups of professionals and significant social agents were performed to collect data. Results identify 4 styles of aging: an opportunity for the change; a natural phase of the life; a moment to compensate and; a moment of abandonment. Conclusions summarize intervention proposals to increase active and participatory ways of ageing in different contexts to help professionals responsible for the services of older people care

Searching for targets for the systemic therapy of mesothelioma.

Malignant mesothelioma is an incurable disease associated with asbestos exposure arising in the pleural cavity and less frequently in the peritoneal cavity. Platinum-based combination chemotherapy with pemetrexed is the established standard of care. Multimodality approaches including surgery and radiotherapy are being investigated. Increasing knowledge about the molecular characteristics of mesothelioma had led to the identification of novel potential targets for systemic therapy. Current evidence suggests pathways activated in response to merlin deficiency, including Pi3K/mTOR and the focal adhesion kinase, as well as immunotherapeutic approaches to be most promising. This review elaborates on the rationale behind targeted approaches that have been and are undergoing exploration in mesothelioma and summarizes available clinical results and ongoing efforts to improve the systemic therapy of mesothelioma.

European Stroke Organisation (ESO) guidelines for the management of temperature in patients with acute ischemic stroke.

BACKGROUND: Hyperthermia is a frequent complication in patients with acute ischemic stroke. On the other hand, therapeutically induced hypothermia has shown promising potential in animal models of focal cerebral ischemia. This Guideline Document presents the European Stroke Organisation guidelines for the management of temperature in patients with acute ischemic stroke. METHODS: A multidisciplinary group identified related questions and developed its recommendations based on evidence from randomized controlled trials elaborating the Grading of Recommendations Assessment, Development, and Evaluation approach. This Guideline Document was reviewed within the European Stroke Organisation and externally and was approved by the European Stroke Organisation Guidelines Committee and the European Stroke Organisation Executive Committee. RESULTS: We found low-quality evidence, and therefore, we cannot make any recommendation for treating hyperthermia as a means to improve functional outcome and/or survival in patients with acute ischemic stroke and hyperthermia; moderate evidence to suggest against routine prevention of hyperthermia with antipyretics as a means to improve functional outcome and/or survival in patients with acute ischemic stroke and normothermia; very low-quality evidence to suggest against routine induction of hypothermia as a means to improve functional outcome and/or survival in patients with acute ischemic stroke. CONCLUSIONS: The currently available data about the management of temperature in patients with acute ischemic stroke are limited, and the strengths of the recommendations are therefore weak. We call for new randomized controlled trials as well as recruitment of eligible patients to ongoing randomized controlled trials to allow for better-informed recommendations in the future.

Synthesis of highly focused fields with circular polarization at any transverse plane

We develop a method for generating focused vector beams with circular polarization at any transverse plane. Based on the Richards-Wolf vector model, we derive analytical expressions to describe the propagation of these set of beams near the focal area. Since the polarization and the amplitude of the input beam are not uniform, an interferometric system capable of generating spatially-variant polarized beams has to be used. In particular, this wavefront is manipulated by means of spatial light modulators displaying computer generated holograms and subsequently focused using a high numerical aperture objective lens. Experimental results using a NA=0.85 system are provided: irradiance and Stokes images of the focused field at different planes near the focal plane are presented and compared with those obtained by numerical simulation.

O uso da ultra-sonografia no diagnóstico e evolução da apendicite aguda

OBJETIVO: Aproximadamente 35% das apendicites agudas têm diagnóstico clínico pré-operatório duvidoso ou incorreto, particularmente grávidas e crianças. A ultra-sonografia, em virtude do seu baixo custo e facilidade de acesso, tem-se mostrado um método diagnóstico importante. Este estudo propôs-se a demonstrar os principais achados de imagem das diversas fases da apendicite, com o objetivo de auxiliar o ultra-sonografista no diagnóstico precoce desta afecção. MATERIAIS E MÉTODOS: São relatados 14 casos de ultra-sonografias abdominais realizadas no período de janeiro a julho de 2001, em pacientes que se apresentavam com quadro de abdome agudo. O exame foi realizado com transdutores de 3,5 MHz e 7,5 MHz. RESULTADOS: O estudo ultra-sonográfico antes da perfuração demonstra apêndice não compressível, com espessamento e perda focal da definição das paredes. Após a perfuração, o apêndice pode não ser visualizado ao exame de ultra-sonografia, sendo evidenciadas alterações secundárias como efeito de massa, formação de plastrão, liquefação e formação de abscesso, além de ar dentro da coleção. CONCLUSÃO: O diagnóstico precoce da apendicite é essencial para minimizar a morbidade, que se mantém elevada se ocorrer perfuração. Apresentações atípicas resultam em confusão diagnóstica e retarde no tratamento. As principais dificuldades e erros são apendicite retrocecal, apendicite focal ou perfurada.

Pseudolesões hepáticas na ressonância magnética: ensaio iconográfico

A ressonância magnética é uma técnica de grande importância na avaliação do fígado. Assim como na tomografia computadorizada helicoidal, o emprego de aquisições rápidas, em fases diferentes da vascularização hepática, auxilia na detecção e caracterização de tumores. Contudo, algumas armadilhas podem confundir e dificultar a interpretação do exame, simulando lesões parenquimatosas. Estas armadilhas têm forma, localização e características variadas, sendo denominadas de pseudolesões. Podem ser decorrentes de diversos fatores, como alterações perfusionais, esteatose focal, parênquima hepático preservado na esteatose difusa, artefatos, entre outros. É muito importante que sejam reconhecidas, para que não sejam causas de resultados falso-positivos. O objetivo deste ensaio é classificar e ilustrar as diversas pseudolesões hepáticas na ressonância magnética, com breve descrição delas, e alternativas para diferenciá-las das lesões do parênquima.