Emotional behavior in acute stroke : the Lausanne emotion in stroke study

Résumé : Objectif: Etudier les comportements émotionnels chez les patients ayant souffert d'un accident vasculaire cérébral (AVC) Contexte: Les modifications du comportement émotionnel après un AVC sont actuellement bien reconnues mais ont été très peu étudiées dans la phase aigüe de l'AVC. Méthode: Tous les patients présentant un AVC datant de moins de 24 heures ont été inclus prospectivement. Nous avons validé une échelle (the Emotional Behavior Index (EBI)), comprenant 38 qualificatifs, représentant la tristesse, l'agressivité, la désinhibition, l'adaptation, la passivité, l'indifférence et le déni. Les informations cliniques et radiologiques (CT et IRM) ont été obtenues par le biais de notre Registre des AVC. L'analyse statistique a été faite au moyen de tests uni- et multi-variés Résultats: Des 254 patients inclus, 40% présentaient de la tristesse, 49% de la passivité, 17% de l'agressivité, 53% de l'indifférence, 76% de la désinhibition, 18% un manque d'adaptation et 44% une réaction de déni. Plusieurs interactions statistiquement significatives ont été mises en évidence. En effet, la tristesse semble corréler à des antécédents d'alcoolisme (r = p< 0.037), au sexe féminin (r = p<0.028) et à la nature hémorragique de l'AVC (r = p<0.063). L'agressivité corrèle à des antécédents de troubles dépressifs (r = p<0.046) et à la nature hémorragique de l'AVC (r = p<0.06). Le déni corrèle plutôt au sexe masculin (r = p<0.035) et aux lésions hémorragiques (r = p<0.05). Le comportement émotionnel ne corrèle ni au degré et type d'atteinte neurologique, ni à la localisation de l'AVC mais une association entre Les lésions hémorragiques et un comportement agressif a été mis en évidence (p<0.001) de même qu'avec un manque d'adaptation (r = p<0.015), une certaine indifférence (r = p<0.018) et une réaction de déni (r = p<0.045). Conclusion: L'observation systématique des modifications du comportement émotionnel après un AVC suggère que les altérations émotionnelles sont indépendantes de la thymie et de l'atteinte physique et représentent donc probablement des séquelles à part entière de l'AVC. Abstract: Objective: To study emotional behaviors in an acute stroke population. Background: Alterations in emotional behavior after stroke have been recently recognized, but little attention has been paid to these changes in the very acute phase of stroke. Methods: Adult patients presenting with acute stroke were prospectively recruited and studied. We validated the Emotional Behavior Index (EBI), a 38-item scale designed to evaluate behavioral aspects of sadness, aggressiveness, disinhibition, adaptation, passivity, indifference, and denial. Clinical, historical, and imaging (computed tomography/magnetic resonance imaging) data were obtained on each subject through our Stroke Registry. Statistical analysis was performed with both univariate and multivariate tests. Results: Of the 254 patients, 40% showed sadness, 49% passivity, 17% aggressiveness, 53% indifference, 76% disinhibition, 18% lack of adaptation, and 44% denial reactions. Several significant correlations were identified. Sadness was correlated with a personal history of alcohol abuse (r = P < 0.037), female gender (r = P < 0.028), and hemorrhagic nature of the stroke (r = P < 0.063). Aggressiveness was correlated with a personal history of depression (r = P < 0.046) and hemorrhage (r = P < 0.06). Denial was correlated with male gender (r= P < 0.035) and hemorrhagic lesions (r = P < 0.05). Emotional behavior did not correlate with either neurologic impairment or lesion localization, but there was an association between hemorrhage and aggressive behavior (P < 0.001), lack of adaptation (r = P < 0.015), indifference (r = P < 0.018), and denial (r = P < 0.045). Conclusions: Systematic observations of acute emotional behaviors after stroke suggest that emotional alterations are independent of mood and physical status and should be considered as a separate consequence of stroke.

Pintomyia (Pifanomyia) paleotownsendi, a new sand fly from the Miocene amber of Dominican Republic (Diptera: Psychodidae: Phlebotominae)

Phlebotominae includes some vector species, mainly that of leishmaniases, with a very old host-parasite relationship. Some species fossils of this subfamily have been recently described and this paper presents the description of a new sand fly Pintomyia (Pifanomyia) paleotownsendi sp. nov in amber. The gonostyle present four spines, being one apical, one external superior implanted close to the apical third, one external inferior in the middle of the structure and one internal implanted in the basal third. This disposition of the spines may separate the new species from others in the sub genus.

Observations on Eimeria species of Dasyprocta leporina (Linnaeus, 1758)(Rodentia: Dasyproctidae) from the state of Pará, North Brazil

Redescriptions are given of the mature oocysts of Eimeria aguti Carini 1935, E. cotiae Carini, 1935 and E. paraensis Carini, 1935, in the faeces of five specimens of the rodent Dasyprocta leporina (Rodentia: Dasyproctidae) from the state of Pará, North Brazil. New information is provided on the sporulation time of these parasites and the prepatent period in experimentally infected D. leporina. Some endogenous stages of E. cotiae are described in the epithelial cells of the ileum, and the absence of any oocysts in the gall-bladder contents of the infected animals indicates that the intestine is also the site of development of E. aguti and E. paraensis. Difficulties in separating E. cotiae and E. paraensis on morphology of the oocysts are discussed. The oocysts of both parasites share many structural features and have a wide size range. It is concluded that although it is at present best to maintain these names, the possibility exists that they were separately given to oocysts of smaller dimensions (E. cotiae) and larger dimensions (E. paraensis) of a single parasite. Location of an endogenous site of development for E. paraensis that is distinctly separate from that of E. cotiae might establish more definitely the separate specific status of the two parasites.

Patterns of pain freedom response in 497 cases with classical trigeminal neuralgia and at least one year of follow-up treated by gamma knife radiosurgery

Purpose: To identify patterns of initially pain freedom response in patients with classical trigeminal neuralgia (CTN) with Gamma Knife surgery (GKS) and to compare their associated hypoesthesia and recurrence rates. Methods: In this study we analysed only 497 patients treated between July 1992 and November 2010, with a follow-up longer than 1 year, after excluding megadolichobasilar artery and multiple sclerosis related trigeminal neuralgia, as well as the second GKS treatments so as to have only cases with CTN and single radiosurgical treatment. GKS using a Gamma Knife (model B or C or Perfexion) was performed, based on both MRI and computer tomography (CT) targeting. A single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.8 mm (range 4.5-14) anteriorly to the emergence of the nerve. A median maximum dose of 85 Gy (range 70-90) was delivered. After empiric methods but also by using a chart with clear cut-off periods of pain free distribution, we were able to divide the initially pain free patients into 3 separate groups: within the first 48 hours, after 48 hours till 30 days and after 30 days, respectively. Results: The median follow- up period was 43.75 months (range 12-174.41). Four hundred and fifty-four patients (91.75%) were initially pain free in a median time of 10 days (range 1-459): 169 (37.2%) became pain free within the first 48 hours (pf<=48 h), compared to 194 (42.8%) between the 3-rd day and the day 30 (pf (>48 h, <=30 d)), inclusively and 91 (20%) patients after 30 days (pf>30d). Differences in terms of postoperative hypoesthesia were found with a p value of 0.014 as follows: the group pf<=48 h had 18 (13.7%) compared to pf (>48 h, <=30 d) with 30 (19%) and pf>30d with 22 (30.5%) patients developing a postoperative GKS hypoesthesia. One hundred and fifty seven (34.4%) patients initially pain free experienced a recurrence with a median delay of 24 months (range 0.62-150.06). There were no statistically significant differences between the three groups concerning recurrence (p value of 0.515). Conclusions: An important number of patients (169 cases, 37.2%) became pain free in the first 48 hours. Hypoesthesia rate was higher within the group becoming pain free after 30 days with a statistically significant difference between the three populations (p= 0.014). Further analysis will eventually help to elucidate the differences observed among groups.

Single-stranded oligonucleotide-mediated in vivo gene repair in the rd1 retina.

PURPOSE: The aim of this study was to test whether oligonucleotide-targeted gene repair can correct the point mutation in genomic DNA of PDE6b(rd1) (rd1) mouse retinas in vivo. METHODS: Oligonucleotides (ODNs) of 25 nucleotide length and complementary to genomic sequence subsuming the rd1 point mutation in the gene encoding the beta-subunit of rod photoreceptor cGMP-phosphodiesterase (beta-PDE), were synthesized with a wild type nucleotide base at the rd1 point mutation position. Control ODNs contained the same nucleotide bases as the wild type ODNs but with varying degrees of sequence mismatch. We previously developed a repeatable and relatively non-invasive technique to enhance ODN delivery to photoreceptor nuclei using transpalpebral iontophoresis prior to intravitreal ODN injection. Three such treatments were performed on C3H/henJ (rd1) mouse pups before postnatal day (PN) 9. Treatment outcomes were evaluated at PN28 or PN33, when retinal degeneration was nearly complete in the untreated rd1 mice. The effect of treatment on photoreceptor survival was evaluated by counting the number of nuclei of photoreceptor cells and by assessing rhodopsin immunohistochemistry on flat-mount retinas and sections. Gene repair in the retina was quantified by allele-specific real time PCR and by detection of beta-PDE-immunoreactive photoreceptors. Confirmatory experiments were conducted using independent rd1 colonies in separate laboratories. These experiments had an additional negative control ODN that contained the rd1 mutant nucleotide base at the rd1 point mutation site such that the sole difference between treatment with wild type and control ODN was the single base at the rd1 point mutation site. RESULTS: Iontophoresis enhanced the penetration of intravitreally injected ODNs in all retinal layers. Using this delivery technique, significant survival of photoreceptors was observed in retinas from eyes treated with wild type ODNs but not control ODNs as demonstrated by cell counting and rhodopsin immunoreactivity at PN28. Beta-PDE immunoreactivity was present in retinas from eyes treated with wild type ODN but not from those treated with control ODNs. Gene correction demonstrated by allele-specific real time PCR and by counts of beta-PDE-immunoreactive cells was estimated at 0.2%. Independent confirmatory experiments showed that retinas from eyes treated with wild type ODN contained many more rhodopsin immunoreactive cells compared to retinas treated with control (rd1 sequence) ODN, even when harvested at PN33. CONCLUSIONS: Short ODNs can be delivered with repeatable efficiency to mouse photoreceptor cells in vivo using a combination of intravitreal injection and iontophoresis. Delivery of therapeutic ODNs to rd1 mouse eyes resulted in genomic DNA conversion from mutant to wild type sequence, low but observable beta-PDE immunoreactivity, and preservation of rhodopsin immunopositive cells in the outer nuclear layer, suggesting that ODN-directed gene repair occurred and preserved rod photoreceptor cells. Effects were not seen in eyes treated with buffer or with ODNs having the rd1 mutant sequence, a definitive control for this therapeutic approach. Importantly, critical experiments were confirmed in two laboratories by several different researchers using independent mouse colonies and ODN preparations from separate sources. These findings suggest that targeted gene repair can be achieved in the retina following enhanced ODN delivery.

Use of the chicken lysozyme 5' matrix attachment region to generate high producer CHO cell lines.

Scaffold or matrix attachment region (S/MAR) genetic elements have previously been proposed to insulate transgenes from repressive effects linked to their site of integration within the host cell genome. We have evaluated their use in various stable transfection settings to increase the production of recombinant proteins such as monoclonal antibodies from Chinese hamster ovary (CHO) cell lines. Using the green fluorescent protein coding sequence, we show that S/MAR elements mediate a dual effect on the population of transfected cells. First, S/MAR elements almost fully abolish the occurrence of cell clones that express little transgene that may result from transgene integration in an unfavorable chromosomal environment. Second, they increase the overall expression of the transgene over the whole range of expression levels, allowing the detection of cells with significantly higher levels of transgene expression. An optimal setting was identified as the addition of a S/MAR element both in cis (on the transgene expression vector) and in trans (co-transfected on a separate plasmid). When used to express immunoglobulins, the S/MAR element enabled cell clones with high and stable levels of expression to be isolated following the analysis of a few cell lines generated without transgene amplification procedures.

Disseny i implantació de l'estructura informàtica de DaVinci School

Creació d'una infraestructura informàtica d'un centre educatiu, amb xarxes separades per a aules, secretaria i seminaris. Serveis centralitzats en un servidor amb màquines virtuals.

Uso de ODR en las comunidades de desarrollo de software libre

La revolució del programari lliure ha estat i és un dels fenòmens més imprevisibles i de major abast que han sorgit des del desenvolupament de les Tecnologies de la Informació. No obstant això és un fenomen que, a causa de pròpia construcció social i distribuïda, està intrínsecament unit a la noció de conflicte, la manifestació del qual més notòria és la bifurcació o fork. En el present treball analitzem els diferents tipus de conflictes i els mecanismes habitualment emprats per a la resolució dels mateixos, i si formen part dels denominats mètodes alternatius de resolució de controvèrsies en Línia o ODR o si són part d'una categoria diferent i separada.

Autophagy controls IL-1beta secretion by targeting pro-IL-1beta for degradation.

Autophagy is a key regulator of cellular homeostasis that can be activated by pathogen-associated molecules and recently has been shown to influence IL-1β secretion by macrophages. However, the mechanisms behind this are unclear. Here, we describe a novel role for autophagy in regulating the production of IL-1β in antigen-presenting cells. After treatment of macrophages with Toll-like receptor ligands, pro-IL-1β was specifically sequestered into autophagosomes, whereas further activation of autophagy with rapamycin induced the degradation of pro-IL-1β and blocked secretion of the mature cytokine. Inhibition of autophagy promoted the processing and secretion of IL-1β by antigen-presenting cells in an NLRP3- and TRIF-dependent manner. This effect was reduced by inhibition of reactive oxygen species but was independent of NOX2. Induction of autophagy in mice in vivo with rapamycin reduced serum levels of IL-1β in response to challenge with LPS. These data demonstrate that autophagy controls the production of IL-1β through at least two separate mechanisms: by targeting pro-IL-1β for lysosomal degradation and by regulating activation of the NLRP3 inflammasome.

Attrition in the Swiss Household Panel

In this paper, we analyze magnitude and possible selectivity of attrition in first wave respondents in the Swiss Household Panel (SHP), from wave two (2000) through wave seven (2005). After comparing attrition of first wave respondents with that of other panel surveys, we proceed to model selectivity of attrition in two steps: we first build separate waveto- wave models, and second a longitudinal all-wave model. The latter model includes wave interaction effects. The first models allow for tracing of selectivity development, i.e. whether an initial selectivity might compensate or cumulates over time, the second to assessing the effects of the covariates in a specific wave, controlling for the base attrition effect. In particular it allows for the analysis of consequences due to discrete fieldwork events. Our results support the findings in the literature: attritors are in general the younger people and the males, foreigners, the socially and politically "excluded", i.e. those who show little social and political interest and participation, those who are mostly dissatisfied with various aspects in their life, and those who live in households with high unit nonresponse, and who exhibit a worse reporting behavior. This pattern is rather cumulative than compensating over panel waves. Excessive attrition in two waves presumably caused by two discrete events in the panel is not particularly selective. Still existing variation in selective attrition is worth to be further explored.

Does a shift in host plants trigger speciation in the Alpine leaf beetle Oreina speciosissima (Coleoptera, Chrysomelidae)?

Background: Within the Coleoptera, the largest order in the animal kingdom, the exclusively herbivorous Chrysomelidae are recognized as one of the most species rich beetle families. The evolutionary processes that have fueled radiation into the more than thirty-five thousand currently recognized leaf beetle species remain partly unresolved. The prominent role of leaf beetles in the insect world, their omnipresence across all terrestrial biomes and their economic importance as common agricultural pest organisms make this family particularly interesting for studying the mechanisms that drive diversification. Here we specifically focus on two ecotypes of the alpine leaf beetle Oreina speciosissima (Scop.), which have been shown to exhibit morphological differences in male genitalia roughly corresponding to the subspecies Oreina speciosissima sensu stricto and Oreina speciosissima troglodytes. In general the two ecotypes segregate along an elevation gradient and by host plants: Oreina speciosissima sensu stricto colonizes high forb vegetation at low altitude and Oreina speciosissima troglodytes is found in stone run vegetation at higher elevations. Both host plants and leaf beetles have a patchy geographical distribution. Through use of gene sequencing and genome fingerprinting (AFLP) we analyzed the genetic structure and habitat use of Oreina speciosissima populations from the Swiss Alps to examine whether the two ecotypes have a genetic basis. By investigating a wide range of altitudes and focusing on the structuring effect of habitat types, we aim to provide answers regarding the factors that drive adaptive radiation in this phytophagous leaf beetle.Results: While little phylogenetic resolution was observed based on the sequencing of four DNA regions, the topology and clustering resulting from AFLP genotyping grouped specimens according to their habitat, mostly defined by plant associations. A few specimens with intermediate morphologies clustered with one of the two ecotypes or formed separate clusters consistent with habitat differences. These results were discussed in an ecological speciation framework.Conclusions: The question of whether this case of ecological differentiation occurred in sympatry or allopatry remains open. Still, the observed pattern points towards ongoing divergence between the two ecotypes which is likely driven by a recent shift in host plant use.

Genetic relationships between sympatric populations of Bacillus cereus and Bacillus thuringiensis, as revealed by rep-PCR genomic fingerprinting

The bacterial strain Bacillus cereus is closely related to Bacillus thuringiensis, although any genetic relationship between the two strains is still in debate. Using rep-PCR genomic fingerprinting, we established the genetic relationships between Brazilian sympatric populations of B. cereus and B. thuringiensis simultaneously collected from two geographically separate sites. We observed the formation of both B. thuringiensis and B. cereus clusters, as well as strains of B. cereus that are more closely related to B. thuringiensis than to other B. cereus strains. In addition, lower genetic variability was observed among B. thuringiensis clusters compared to B. cereus clusters, indicating that either the two species should be categorized as separate or that B. thuringiensis may represent a clone from a B. cereus background.

Abnormal EEG Synchronization Correlates with Demyelination in Alzheimer's Disease

Introduction : The pathological processes caused by Alzheimer's disease (AD) supposedly disrupt communication between and within the distributed cortical networks due to the dysfunction/loss of synapses and myelination breakdown. Indeed, recently (Knyazeva et al. 2008), we have revealed the whole-head topography of EEG synchronization specific to AD. Here we analyze whether and how these abnormalities of synchronization are related to the demyelination of cortico-cortical fibers. Methods : Fifteen newly diagnosed AD patients (CDR 0.5-1) and 15 controls matched for age, participated in the study. Their multichannel (128) EEGs were recorded during 3-5 min at rest. They were submitted to the multivariate phase synchronization (MPS) analysis for mapping regional synchronization. To obtain individual whole-head maps, the MPS was computed for each sensor considering its 2nd nearest topographical neighbors. Separate calculations were performed for the delta, theta, alpha-1/−2, and beta-1/−2 EEG bands. The same subjects were scanned on a 3 Tesla Philips scanner. The protocol included a high-resolution T1-weighted sequence and a Magnetization Transfer Imaging (MTI) acquisition. For each subject, we defined a 3mm thick layer of white matter exactly below the cortical gray matter. The magnetization transfer ratio (MTR) - an estimator of myelination - was calculated for this layer in 39 Brodmann-defined ROIs per hemisphere. To assess the between-group differences, we used a permutation version of Hotelling's T2 test or two-sample T-test (Pcorrected <0.05). For correlation analysis, Spearman Rank Correlation was calculated. Results : In AD patients, we have found an abnormal landscape of synchronization characterized by a decrease in MPS over the fronto-temporal region of the left hemisphere and an increase over the temporo-parieto-occipital regions bilaterally. Also, we have shown a widespread decrease in regional MTR in the AD patients for all the areas excluding motor, premotor, and primary sensory ones. Assuming that AD-related changes in synchronization are associated with demyelination, we hypothesized a correlation between the regional MTR values and MPS values in the hypo- and hyper-synchronized clusters. We found that MPS in the left fronto-temporal hypo-synchronized cluster directly correlates with myelination in BA42-46 of the left hemisphere: the lower the myelination in individual patients, the lower the EEG synchronization. By contrast, in the posterior hyper-synchronized cluster, MPS inversely correlated with myelination, i.e., the lower the myelination, the higher the synchronization. This posterior hyper-synchronization, more characteristic for early-onset AD, probably, results from the initial effect of the disease on cortical inhibition, reducing cortical capacity for decoupling irrelevant connections. Remarkably, it showed different topography of correlations in early- vs. late-onset patients. In the early-onset patients, hyper-synchronization was mainly related to demyelination in posterior BAs, the effect being significant in all the EEG frequency bands. In the late-onset patients, widely distributed correlations were significant for the EEG delta band, suggesting an interaction between the cerebral manifestations of AD and the age of its onset, i.e., topographically selective impairment of cortical inhibition in early-onset AD vs. its wide-spread weakening in old age. Conclusions : Overall, our results document that the degradation of white matter is a significant factor of AD pathogenesis leading to functional dysconnection, the latter being reflected in EEG synchronization abnormalities.

Gènere i bilingüisme: connectant experiències i teories. Introductory paper in Santaemilia, José, Patricia Bou, Sergio Maruenda i Gora Zaragoza International Perspectives on Gender and Language

Peer-reviewed

Alcohol intake and the risk of coronary heart disease in the Spanish EPIC

Background: The association between alcohol consumption and coronary heart disease (CHD) has been widely studied. Most of these studies have concluded that moderate alcohol intake reduces the risk of CHD. There are numerous discussions regarding whether this association is causal or biased. The objective of this paper is to analyse the association between alcohol intake and CHD risk in the Spanish cohort of the European Prospective Investigation into Cancer (EPIC). Methods: Participants from the EPIC Spanish cohort were included (15 630 men and 25 808 women). The median follow-up period was 10 years. Ethanol intake was calculated using a validated dietary history questionnaire. Participants with a definite CHD event were considered cases. A Cox regression model adjusted for relevant co-variables and stratified by age was produced. Separate models were carried out for men and women. Results: The crude CHD incidence rate was 300.6/100 000 person-years for men and 47.9/100 000 person-years for women. Moderate, high and very high consumption was associated with a reduced risk of CHD in men: hazard ratio 0.90 (95% CI 0.56 to 1.44) for former drinkers, 0.65 (95% CI 0.41 to 1.04) for low, 0.49 (95% CI 0.32 to 0.76) for moderate, 0.46 (95% CI 0.30 to 0.71) for high and 0.50 (95% CI 0.29 to 0.85) for very high consumers. A negative association was found in women, with p values above 0.05 in all categories. Conclusions: Alcohol intake in men aged 29–69 years was associated with a more than 30% lower CHD incidence. This study is based on a large prospective cohort study and is free of the abstainer error.