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.

Alzheimer Disease Diagnosis based on Automatic Spontaneous Speech Analysis

Alzheimer’s disease (AD) is the most prevalent form of progressive degenerative dementia and it has a high socio-economic impact in Western countries, therefore is one of the most active research areas today. Its diagnosis is sometimes made by excluding other dementias, and definitive confirmation must be done trough a post-mortem study of the brain tissue of the patient. The purpose of this paper is to contribute to improvement of early diagnosis of AD and its degree of severity, from an automatic analysis performed by non-invasive intelligent methods. The methods selected in this case are Automatic Spontaneous Speech Analysis (ASSA) and Emotional Temperature (ET), that have the great advantage of being non invasive, low cost and without any side effects.

Spontaneous Speech and Emotional Response modeling based on One-class classifier oriented to Alzheimer Disease diagnosis

The purpose of our project is to contribute to earlier diagnosis of AD and better estimates of its severity by using automatic analysis performed through new biomarkers extracted from non-invasive intelligent methods. The methods selected in this case are speech biomarkers oriented to Sponta-neous Speech and Emotional Response Analysis. Thus the main goal of the present work is feature search in Spontaneous Speech oriented to pre-clinical evaluation for the definition of test for AD diagnosis by One-class classifier. One-class classifi-cation problem differs from multi-class classifier in one essen-tial aspect. In one-class classification it is assumed that only information of one of the classes, the target class, is available. In this work we explore the problem of imbalanced datasets that is particularly crucial in applications where the goal is to maximize recognition of the minority class as in medical diag-nosis. The use of information about outlier and Fractal Dimen-sion features improves the system performance.

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.

Valor da varredura com iodo antes da terapia ablativa em pacientes com carcinoma de tireóide

OBJETIVO: Avaliar a relevância clínica da varredura pré-dose ablativa em pacientes com carcinoma diferenciado de tireóide. MATERIAIS E MÉTODOS: Analisamos a varredura com 131I e a tireoglobulina (Tg) sérica em hipotireoidismo antes da primeira terapia ablativa em 100 pacientes submetidos a tireoidectomia total, considerando a varredura clinicamente importante quando revelou metástases ressecáveis ou que foram tratadas com doses maiores que a inicialmente proposta (100 mCi de 131I), além dos casos sem captação e com Tg < 5 ng/ml, que não receberam radioiodoterapia. RESULTADOS: A varredura revelou captação correspondente a metástases linfonodais em dez pacientes (10%), metástases distantes em cinco (5%), apenas em leito tireoidiano em 76 (76%) e foi negativa em nove (9%), sendo clinicamente relevante (indicando cirurgia, aumento da dose ou dispensando a radioiodoterapia) em 18% dos pacientes. Nos pacientes com Tg > 10 ng/ml a varredura influenciou a conduta em 41% dos casos pela presença de metástases, e naqueles com Tg < 10 ng/ml em apenas 10%, na maioria por não receberem radioiodo. CONCLUSÃO: A varredura pré-dose ablativa fornece informacões clinicamente importantes (presença de metástases) em muitos pacientes com Tg > 10 ng/ml, sendo indicada nesta condição.

Avaliação pós-operatória do tratamento endovascular de aneurismas da aorta abdominal por angiotomografia com multidetectores

OBJETIVO: Este estudo tem como objetivo a avaliação pós-operatória do tratamento endovascular de aneurismas da aorta abdominal por angiotomografia com multidetectores. MATERIAIS E MÉTODOS: Foram analisadas, retrospectivamente, angiotomografias de 166 pacientes (137 homens e 29 mulheres) com idade média de 73 anos portadores de aneurisma da aorta abdominal submetidos a terapêutica endovascular, no período de junho de 2005 a agosto de 2006. Os exames foram feitos em tomógrafo multidetector de 64 canais e os parâmetros adotados foram: colimação, 0,625 mm; pitch, 0,6-1; mAs, 300-400; kV, 120. Em todos os casos foi utilizado meio de contraste iodado não-iônico (350 mg/ml) administrado por meio de bomba infusora, com fluxo de 4 ml/s a 5 ml/s e com volume variável de 70 ml a 100 ml. Os exames foram avaliados quanto à presença de complicações. RESULTADOS: Dos 166 exames realizados, 93 pacientes não apresentaram complicações e 73 apresentaram os seguintes achados: endoleak (n=37), trombose circunferencial da endoprótese (n=29), angulação (n=17), coleção no sítio de punção (n=10), migração da prótese (n=7), dissecção dos vasos de acesso (n=7) e oclusão (n=6). CONCLUSÃO: O endoleak foi a complicação mais prevalente em nosso estudo, sendo o tipo II o mais comum.

Cintilografia de perfusão miocárdica sob baixa dose de dobutamina na identificação do miocárdio viável

OBJETIVO: Verificar se a cintilografia de perfusão miocárdica duoisotópica(99mTc-sestamibi/tálio-201), método de alta sensibilidade para identificação do músculo viável, tem sua especificidade aumentada com a inclusão de informações sobre reserva contrátil miocárdica obtidas simultaneamente através de gated SPECT na vigência de baixas doses de dobutamina de forma semelhante ao ecocardiograma. MATERIAIS E MÉTODOS: Estudaram-se 260 segmentos miocárdicos de 13 pacientes com infarto do miocárdio, encaminhados para pesquisa de viabilidade antes do procedimento de revascularização. Avaliaram-se a integridade celular e a reserva contrátil pela cintilografia de perfusão miocárdica duoisotópica com imagens de repouso e redistribuição do tálio-201 e de estresse (99mTc-sestamibi gated SPECT), em condições basais e na vigência de baixas doses de dobutamina. A melhora do desempenho contrátil em controle cintilográfico pós-revascularização (99mTc-sestamibi gated SPECT) confirmava a presença de viabilidade. Para análise dos resultados quantificaram-se os parâmetros funcionais dos segmentos miocárdicos nas diferentes etapas do estudo, estratificando-os quanto à viabilidade para posterior comparação funcional pós-revascularização. RESULTADOS: No tratamento estatístico a análise do espessamento sistólico se destacou como parâmetro de avaliação da reserva contrátil miocárdica pelo método, mostrando tendência a incremento na especificidade (84%), demonstrando valores superiores aos da literatura. CONCLUSÃO: O método tende a apresentar contribuições efetivas na busca do miocárdio viável.

Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.

Doença de Caroli complicada com abscesso hepático: relato de caso

A doença de Caroli é uma má-formação congênita rara caracterizada por dilatações multifocais dos ductos biliares intra-hepáticos que predispõem a colestase e episódios recorrentes de colangite. Descrevemos o caso de um paciente jovem diagnosticado com doença de Caroli, por meio da colangiorressonância, que complicou com abscesso hepático e foi submetido a drenagem cirúrgica.

Negative feedback regulation of calcineurin-dependent Prz1 transcription factor by the CaMKK-CaMK1 axis in fission yeast

Calcium signals trigger the translocation of the Prz1 transcription factor from the cytoplasm to the nucleus. The process is regulated by the calciumactivated phosphatase calcineurin, which activates Prz1 thereby maintaining active transcription during calcium signalling. When calcium signalling ceases, Prz1 is inactivated by phosphorylation and exported to the cytoplasm. In budding yeast and mammalian cells, different kinases have been reported to counter calcineurin activity and regulate nuclear export. Here, we show that the Ca2+/calmodulin-dependent kinase Cmk1 is first phosphorylated and activated by the newly identified kinase CaMKK2 homologue, Ckk2, in response to Ca2+. Then, active Cmk1 binds, phosphorylates and inactivates Prz1 transcription activity whilst at the same time cmk1 expression is enhanced by Prz1 in response to Ca2+. Furthermore, Cdc25 phosphatase is also phosphorylated by Cmk1, inducing cell cycle arrest in response to an increase in Ca2+. Moreover, cmk1 deletion shows a high tolerance to chronic exposure to Ca2+, due to the lack of cell cycle inhibition and elevated Prz1 activity. This work reveals that Cmk1 kinase activated by the newly identified Ckk2 counteracts calcineurin function by negatively regulating Prz1 activity which in turn is involved in activating cmk1 gene transcription. These results are the first insights into Cmk1 and Ckk2 function in Schizosaccharomyces pombe.

Long-term controlled GDNF over-expression reduces dopamine transporter activity without affecting tyrosine hydroxylase expression in the rat mesostriatal system.

The dopamine (DA) transporter (DAT) is a plasma membrane glycoprotein expressed in dopaminergic (DA-) cells that takes back DA into presynaptic neurons after its release. DAT dysfunction has been involved in different neuro-psychiatric disorders including Parkinson's disease (PD). On the other hand, numerous studies support that the glial cell line-derived neurotrophic factor (GDNF) has a protective effect on DA-cells. However, studies in rodents show that prolonged GDNF over-expression may cause a tyrosine hydroxylase (TH, the limiting enzyme in DA synthesis) decline. The evidence of TH down-regulation suggests that another player in DA handling, DAT, may also be regulated by prolonged GDNF over-expression, and the possibility that this effect is induced at GDNF expression levels lower than those inducing TH down-regulation. This issue was investigated here using intrastriatal injections of a tetracycline-inducible adeno-associated viral vector expressing human GDNF cDNA (AAV-tetON-GDNF) in rats, and doxycycline (DOX; 0.01, 0.03, 0.5 and 3mg/ml) in the drinking water during 5weeks. We found that 3mg/ml DOX promotes an increase in striatal GDNF expression of 12× basal GDNF levels and both DA uptake decrease and TH down-regulation in its native and Ser40 phosphorylated forms. However, 0.5mg/ml DOX promotes a GDNF expression increase of 3× basal GDNF levels with DA uptake decrease but not TH down-regulation. The use of western-blot under non-reducing conditions, co-immunoprecipitation and in situ proximity ligation assay revealed that the DA uptake decrease is associated with the formation of DAT dimers and an increase in DAT-α-synuclein interactions, without changes in total DAT levels or its compartmental distribution. In conclusion, at appropriate GDNF transduction levels, DA uptake is regulated through DAT protein-protein interactions without interfering with DA synthesis.

Implementació d'un sistema de gestió de cursos (Course Management) al Campus Virtual de la UdL

Aquest projecte pretén aconseguir un Campus Virtual més flexible i més obert, on el professorat pugui fer una gestió més acurada i específica dels seus espais de docència, a més de poder crear-se d’altres espais organitzant els grups de matrícula de la forma que més li convingui. La idea és canviar la manera com s’aprovisiona actualment el Campus Virtual amb les dades de gestió acadèmica per tal d’aconseguir un campus on el professorat tingui totes les eines i dades disponibles per a que les pugui utilitzar de la manera que cregui més adient, i no d’una manera predefinida i tancada com es feia fins ara, on el professorat es trobava un espai per cada assignatura que impartia, però no en podia modificar gairebé res. A banda d’aquest objectiu fonamental, aquest treball facilitarà en gran mesura les tasques realitzades per l’equip que gestiona el Campus Virtual en els processos de gestió d’espais de docència i del tractament dels seus participants en sincronització amb els sistemes origen.

Redução de amidas por boranos

Despite the fact that boranes are frequently used in amide reductions, the reaction mechanisms of the involved are note well known. This work presents the results of a bibliographic search on probable amide reduction mechanisms and an analysis of the existing literature. Steric and electronic effects were considered in light of reactivity since it could be concluded that the formation of intermediates and products depends mainly on the substitution patterns of both the boron and nitrogen atoms. Otherwise, results described in the literature for the reactions of boranes, sodium borohydride, lithium aluminum hydride, alkylboranes or haloboranes with others functional groups such as carboxylic acids, esters, ketones and alkenes were analysed with the aim to obtain something about the N-substituted amide reactions employing boranes.

Estudi d'implantació d'un sistema de videoconferència a la Universitat de Lleida

L'auge vertiginós de les tecnologies de la informació i la comunicació (TIC) durant els darrers anys ha creat empremta en la vida quotidiana de la societat mundial, i cada dia hi han més eines al nostre abast que ens faciliten la vida si en sabem treure profit. En l'àmbit universitari, la docència i la recerca universitàries per la seva naturalesa són sectors on ja fa temps que aprofiten les TIC per millorar-ne l'excel·lència. Per exemple, l'e-learning és un tipus d'ensenyament a través d'Internet on professor i alumne poden estar distants geogràficament. La majoria d'universitats ja implementen aquest tipus d'ensenyament comptant amb algun servei de campus virtual com a eina d'ús àmpliament coneguda i gaudeixen de nombrosos avantatges que beneficien tant a l'estudiantat com al professorat i al personal d'administració i serveis. Els sistemes de videoconferència, juntament amb la millora de les connexions a Internet a les llars, conjuminen un altra vessant de les TIC que tenen un gran impacte potencial per a la societat, i així, el fet de poder comunicar-se a distància amb veu i imatge en temps real comporta un estalvi de temps i diners força considerable. L'aprofitament d'aquestes oportunitats que ofereixen les TIC provocarà una reinvenció dels centres educatius i potenciarà un aprenentatge cada cop més pràctic i agradable. L'objectiu del present projecte es estudiar sistemes de videoconferència que puguin ser utilitzats per ells mateixos o de forma integrada al campus virtual de la Universitat de Lleida. A més, també seran objecte d'avaluació els mecanismes i metodologies estàndards per ajudar a la selecció del producte que més s'escaigui a les necessitats de la UdL. Així doncs, forma part de l’abast d’aquest projecte la definició de les necessitats que pot cobrir una eina de videoconferència integrada al campus virtual i l'estudi de les possibles aplicacions futures que se li pot donar per part de la comunitat universitària. I en funció d’aquesta definició, i dels sistemes TIC actuals amb els quals hi pot haver dependència, es definiran els requeriments que posteriorment caldrà valorar per totes les solucions de sistemes de videoconferència destacables per tal de poder seleccionar la més indicada. Durant la seva durada s’abordaran tot un seguit d'etapes per tal de triar un producte final, iniciant en primer lloc l'anàlisi prèvia de l'escenari plantejat, l'anàlisi de requeriments de la universitat, l'estudi de metodologies de valoració de projectes o eines informàtiques, la recerca de productes de videoconferència destacables i la posterior valoració, l'estudi de costs i retorn de la inversió del projecte, i finalment, la definició d'un escenari de pla pilot dins la pròpia universitat