Strategic Adaptation in Function of Chronicity of Schizophrenic Symptoms During A Fluency Task: An fMRI Study

Background: Language processing abnormalities and executive difficulties are hallmark features of schizophrenia. The objective of this study is to assess the blood oxygenation level-dependent (BOLD) response at two different stages of the illness (i.e. comparison between adolescents and adults with schizophrenic symptoms) during a fluency task.Methods: BOLD responses during a covert verbal fluency task were compared between 11 psychotic adolescents with schizophrenic symptoms (mean age 16,9 years) and 14 adults with schizophrenia (mean age 33,4 years). fMRI data were analyzed with standard routine of spm5.Results: First, expected activation's network was found for both groups, separately. Secondly, adolescents showed greater activation in left rolandic opercule (BA 48), left angular (BA 39) and right hippocampus compared to adults. Thirdly, adults demonstrated greater activation in presupplementary motor area (BA 6) and in precentral area (BA 4) compared to adolescents.Conclusions: The adolescents seemed to recruit a verbal network (Broca and Wernicke) and memory abilities to perform a fluency task. In contrast, adults seemed to recruit more executive function abilities to perform a similar task. Despite the evolution of schizophrenia, which is known to have a deleterious influence on the prefrontal cortex development, adult patients seemed to be able to recruit such areas to perform a verbal fluency / executive function task.

La programmmation foetale de la dysfonction vasculaire pulmonaire chez la souris : rôle des mécanismes épigénétiques = Fetal programming of pulmonary vascular dysfunction in mice : role of epigenetic mechanisms

Rapport de synthèseDes événements pathologiques survenant pendant la période foetale prédisposent la descendance aux maladies cardiovasculaires systémiques. Il existe peu de connaissances au sujet de la circulation pulmonaire et encore moins quant aux mécanismes sous-jacents. La sous-alimentation maternelle pendant la grossesse peut représenter un modèle d'investigation de ces mécanismes, parce que chez l'animal et l'homme elle est associée à une dysfonction vasculaire systémique chez la progéniture. Chez le rat, la diète restrictive pendant la grossesse induit une augmentation du stress oxydatif dans le placenta. Les dérivés de l'oxygène sont connus pour induire des altérations épigénétiques et peuvent traverser la barrière placentaire. Nous avons dès lors spéculé que chez la souris la diète restrictive pendant la grossesse induit une dysfonction vasculaire pulmonaire chez sa progéniture qui serait liée à un mécanisme épigénétique.Pour tester cette hypothèse, nous avons examiné la fonction vasculaire pulmonaire et la méthylation de l'ADN pulmonaire à la fin de 2 semaines d'exposition à l'hypoxie chez la progéniture de souris soumises à une diète restrictive pendant la grossesse et des souris contrôles. Nous avons trouvé que la vasodilatation endothélium-dépendante de l'artère pulmonaire in vitro était défectueuse, et que l'hypertension pulmonaire et l'hypertrophie ventriculaire droite induites par l'hypoxie in vivo étaient exagérées chez la progéniture de souris soumises à une diète restrictive pendant la grossesse. Cette dysfonction vasculaire pulmonaire était associée avec une altération de la méthylation de l'ADN pulmonaire. L'administration d'inhibiteurs de la déacétylase des histones, le Butyrate et la Trichostatine-A à la progéniture de souris soumises à une diète restrictive pendant la grossesse a normalisé la méthylation de l'ADN et la fonction vasculaire pulmonaire. Finalement, l'administration du nitroxyde Tempol aux mères durant la diète restrictive pendant la grossesse a prévenu la dysfonction vasculaire et la dysméthylation chez la progéniture.Ces découvertes démontrent que chez la souris la sous-alimentation pendant la gestation induit une dysfonction vasculaire chez la progéniture qui est causée par un mécanisme épigénétique. Il est possible qu'un mécanisme similaire soit impliqué dans la programmation foetale de la dysfonction vasculaire chez les humains.

Programming of marginal zone B-cell fate by basic Kruppel-like factor (BKLF/KLF3).

Splenic marginal zone (MZ) B cells are a lineage distinct from follicular and peritoneal B1 B cells. They are located next to the marginal sinus where blood is released. Here they pick up antigens and shuttle the load onto follicular dendritic cells inside the follicle. On activation, MZ B cells rapidly differentiate into plasmablasts secreting antibodies, thereby mediating humoral immune responses against blood-borne type 2 T-independent antigens. As Krüppel-like factors are implicated in cell differentiation/function in various tissues, we studied the function of basic Krüppel-like factor (BKLF/KLF3) in B cells. Whereas B-cell development in the bone marrow of KLF3-transgenic mice was unaffected, MZ B-cell numbers in spleen were increased considerably. As revealed in chimeric mice, this occurred cell autonomously, increasing both MZ and peritoneal B1 B-cell subsets. Comparing KLF3-transgenic and nontransgenic follicular B cells by RNA-microarray revealed that KLF3 regulates a subset of genes that was similarly up-regulated/down-regulated on normal MZ B-cell differentiation. Indeed, KLF3 expression overcame the lack of MZ B cells caused by different genetic alterations, such as CD19-deficiency or blockade of B-cell activating factor-receptor signaling, indicating that KLF3 may complement alternative nuclear factor-κB signaling. Thus, KLF3 is a driving force toward MZ B-cell maturation.

Performance in a complex task and breathing under odor exposure.

We investigated the influences of odor exposure on performance and on breathing measures. The task was composed of tracking, short-term memory, and peripheral reaction parts. During rest or while performing the task, 12 participants were exposed to 4 different odors in 2 intensities. The higher intensity of the malodors induced a short-term decrement in mean inspiration flow (Vi/Ti) after stimulus onset and impaired performance in the short-term memory task, as compared with control trials; no effect was found for the positively judged odors. The study suggests that a distractor as simple as a bad smell may pull a person off task, however briefly, and may result in a detriment to performance. Actual or potential applications of this research involve designing or securing tasks in such a way that a brief withdrawal of attention does not have fatal consequences.

Plastic modifications within inhibitory control networks induced by practicing a stop-signal task: an electrical neuroimaging study.

INTRODUCTION: Inhibitory control refers to our ability to suppress ongoing motor, affective or cognitive processes and mostly depends on a fronto-basal brain network. Inhibitory control deficits participate in the emergence of several prominent psychiatric conditions, including attention deficit/hyperactivity disorder or addiction. The rehabilitation of these pathologies might therefore benefit from training-based behavioral interventions aiming at improving inhibitory control proficiency and normalizing the underlying neurophysiological mechanisms. The development of an efficient inhibitory control training regimen first requires determining the effects of practicing inhibition tasks. METHODS: We addressed this question by contrasting behavioral performance and electrical neuroimaging analyses of event-related potentials (ERPs) recorded from humans at the beginning versus the end of 1 h of practice on a stop-signal task (SST) involving the withholding of responses when a stop signal was presented during a speeded auditory discrimination task. RESULTS: Practicing a short SST improved behavioral performance. Electrophysiologically, ERPs differed topographically at 200 msec post-stimulus onset, indicative of the engagement of distinct brain network with learning. Source estimations localized this effect within the inferior frontal gyrus, the pre-supplementary motor area and the basal ganglia. CONCLUSION: Our collective results indicate that behavioral and brain responses during an inhibitory control task are subject to fast plastic changes and provide evidence that high-order fronto-basal executive networks can be modified by practicing a SST.

Parenteral anticoagulants in heart disease: Current status and perspectives (Section II). Position Paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease.

Anticoagulants are a mainstay of cardiovascular therapy, and parenteral anticoagulants have widespread use in cardiology, especially in acute situations. Parenteral anticoagulants include unfractionated heparin, low-molecular-weight heparins, the synthetic pentasaccharides fondaparinux, idraparinux and idrabiotaparinux, and parenteral direct thrombin inhibitors. The several shortcomings of unfractionated heparin and of low-molecular-weight heparins have prompted the development of the other newer agents. Here we review the mechanisms of action, pharmacological properties and side effects of parenteral anticoagulants used in the management of coronary heart disease treated with or without percutaneous coronary interventions, cardioversion for atrial fibrillation, and prosthetic heart valves and valve repair. Using an evidence-based approach, we describe the results of completed clinical trials, highlight ongoing research with currently available agents, and recommend therapeutic options for specific heart diseases.

Hipertensión y edema pulmonar de altura. Rol de la disfunción endotelial y de la programación fetal [Pulmonary hypertension and lung edema at high altitude. Role of endothelial dysfunction and fetal programming].

High altitude constitutes an exciting natural laboratory for medical research. While initially, the aim of high-altitude research was to understand the adaptation of the organism to hypoxia and find treatments for altitude-related diseases, over the past decade or so, the scope of this research has broadened considerably. Two important observations led to the foundation for the broadening of the scientific scope of high-altitude research. First, high-altitude pulmonary edema (HAPE) represents a unique model which allows studying fundamental mechanisms of pulmonary hypertension and lung edema in humans. Secondly, the ambient hypoxia associated with high-altitude exposure facilitates the detection of pulmonary and systemic vascular dysfunction at an early stage. Here, we review studies that, by capitalizing on these observations, have led to the description of novel mechanisms underpinning lung edema and pulmonary hypertension and to the first direct demonstration of fetal programming of vascular dysfunction in humans.

Septal lesions impair the acquisition of a cued place navigation task: attentional or memory deficit?

These experiments were designed to analyze how medial septal lesions reducing the cholinergic innervation in the hippocampus might affect place learning. Rats with quisqualic lesions of the medial septal area (MS) were trained in a water maze and on a homing table where the escape position was located at a spatially fixed position and further indicated by a salient cue suspended above it. The lesioned rats were significantly impaired in reaching the cued escape platform during training. In addition rats, did not show any discrimination of the training sector during a probe trial in which no platform or cue was present. This impairment remained significant during further training in the absence of the cue. When the cued escape platform was located at an unpredictable spatial location, the MS-lesioned rats showed no deficit and spent more time under the cue than control rats during the probe trial. On the homing board, with a salient object in close proximity to the escape hole, the MS rats showed no deficit in escape latencies, although a significant reduction in spatial memory was observed. However, this was overcome by additional training in the absence of the cue. Under these conditions, rats with septal lesions were prone to develop a pure guidance strategy, whereas normal rats combined a guidance strategy with a memory of the escape position relative to more distant landmarks. The presence of a salient cue appeared to decrease attention to environmental landmarks, thus reducing spatial memory. These data confirm the general hypothesis that MS lesions reduce the capacity to rely on a representation of the relation between several landmarks with different salience.

Fetal programming of pulmonary vascular dysfunction in mice: role of epigenetic mechanisms.

Insults during the fetal period predispose the offspring to systemic cardiovascular disease, but little is known about the pulmonary circulation and the underlying mechanisms. Maternal undernutrition during pregnancy may represent a model to investigate underlying mechanisms, because it is associated with systemic vascular dysfunction in the offspring in animals and humans. In rats, restrictive diet during pregnancy (RDP) increases oxidative stress in the placenta. Oxygen species are known to induce epigenetic alterations and may cross the placental barrier. We hypothesized that RDP in mice induces pulmonary vascular dysfunction in the offspring that is related to an epigenetic mechanism. To test this hypothesis, we assessed pulmonary vascular function and lung DNA methylation in offspring of RDP and in control mice at the end of a 2-wk exposure to hypoxia. We found that endothelium-dependent pulmonary artery vasodilation in vitro was impaired and hypoxia-induced pulmonary hypertension and right ventricular hypertrophy in vivo were exaggerated in offspring of RDP. This pulmonary vascular dysfunction was associated with altered lung DNA methylation. Administration of the histone deacetylase inhibitors butyrate and trichostatin A to offspring of RDP normalized pulmonary DNA methylation and vascular function. Finally, administration of the nitroxide Tempol to the mother during RDP prevented vascular dysfunction and dysmethylation in the offspring. These findings demonstrate that in mice undernutrition during gestation induces pulmonary vascular dysfunction in the offspring by an epigenetic mechanism. A similar mechanism may be involved in the fetal programming of vascular dysfunction in humans.