The influence of attachment on perceived stress and cortisol response to acute stress in women sexually abused in childhood or adolescence.

The long-term implications of sexual abuse in childhood or adolescence (CSA) have been relatively well documented regarding attachment (disorganized attachment in childhood, unresolved trauma in adulthood), stress reactions (altered patterns of stress reactivity under experimental conditions), and psychopathology. Attachment has been shown to mediate the implications of CSA, namely on psychopathology. The implication of attachment on stress responses of abused persons has not been documented. Twenty-seven 20-46 years old women who had experienced episodes of CSA, and 17 controls have been interviewed using the Adult Attachment Interview. Sixty-three percent of abused women presented an unresolved trauma (12% for the controls). Thirty-six women (14 controls and 22 abused) came again to the laboratory for a session involving an experimental stress challenge (TSST). Subjects provided repeated appreciations of perceived stress on visual analogue scales and saliva samples were collected to assay cortisol levels. Whereas abused women with unresolved trauma showed the highest levels of perceived stress, they simultaneously presented the most suppressed cortisol reactions (there were significant post hoc differences between "unresolved abused" and controls on the increase of perceived stress and on cortisol recovery after the acute stress). It is suggested that important stressful experiences (such as CSA), especially when they have not been psychologically assimilated, may cause a disconnection, during subsequent mildly stressful circumstances, between the perception of stress and natural defensive body reactions.

Differential migration of in vivo primed B and T lymphocytes to lymphoid and non-lymphoid organs.

Our study describes tissue-specific migration of T and B cells during a localized anti-viral immune response. After mouse mammary tumor virus (MMTV) injection, B lymphocytes of the draining lymph node become infected and present a retroviral superantigen to CD4(+) T lymphocytes. Infected B cells receive superantigen-mediated help in a fashion comparable to classical immune responses. To investigate the fate of T and B lymphocytes that had interacted via cognate help in the same peripheral lymph node microenvironment we adoptively transferred them into naive recipients. Here we show that MMTV-infected B cells and superantigen-stimulated T cells were programmed to migrate to distinct sites of the body. Plasmablasts but not T cells migrated to the mammary gland and activated alpha4beta1 integrins were found to have a crucial role in the migration to the mammary gland. In contrast, T cells had a much higher affinity for secondary lymphoid organs and large intestine. This demonstrates that upon antigen-driven B and T lymphocyte interaction in the local draining lymph node a subset-specific homing program for B and T lymphocytes is induced.

Adaption of Courses and Learning Environment to the User Context in dotLRN

The explosive growth of Internet during the last years has been reflected in the ever-increasing amount of the diversity and heterogeneity of user preferences, types and features of devices and access networks. Usually the heterogeneity in the context of the users which request Web contents is not taken into account by the servers that deliver them implying that these contents will not always suit their needs. In the particular case of e-learning platforms this issue is especially critical due to the fact that it puts at stake the knowledge acquired by their users. In the following paper we present a system that aims to provide the dotLRN e-learning platform with the capability to adapt to its users context. By integrating dotLRN with a multi-agent hypermedia system, online courses being undertaken by students as well as their learning environment are adapted in real time

Contribution of genome-wide significant single-nucleotide polymorphisms and antiretroviral therapy to dyslipidemia in HIV-infected individuals : a longitudinal study

Rapport de synthèse :Les individus HIV-positifs constituent une population à risque pour les maladies cardiovasculaires telles que |'infarctus cardiaque ou cérébrale. Celles-ci découlent d'une formation accélérée d'athéroscIérose. Ces pathologies s'expliquent en grande partie par une dyslipidémie observée au sein de cette population et qui sont dues à des facteurs externes tels que : l'immunosuppression avancée, la virémie non-contrôlée, et les effets de la thérapie antirétrovirale. Récemment, des polymorphismes nucléotidiques simples (SNP) associés à la dyslipidémie ont été mis en évidence d'une manière globale par des Genome-Wide Association Studies (GWAS). Le but principal de cette étude est d'éva|uer et de valider |'effet cumulatif des SNP identifiés dans ces GWAS pour la dyslipidémie chez des patients HIV-positifs. De plus, |'identification des facteurs non-génétiques qui contribuent à la dyslipidémie démontrent |'importance des facteurs externes, tels que mentionnés ci- dessus, et en particulier à ceux de la thérapie antirétrovirale.Les participants de l'étude proviennent de trois groupes: 426 personnes sélectionnées pour une étude précédente, 222 personnes sélectionnées de façon arbitraire dans la "Cohorte HIV Suisse" et 103 personnes sélectionnées avec un "New-Onset Diabetes mellitus" identifiées lors d'études précédentes. Ces individus ont contribué à plus de 34'000 mesures de lipides sur une durée moyenne supérieure à 7 ans. Pour l'étude, 33 SNP identifiés dans des GWAS et 9 SNP identifiés dans d'autres études publiées dans la littérature non-couverte par des GWAS ont été repris. Le génotypage a été complété pour 745 (99.2%) des 751 participants. Pour les analyses statistiques, les thérapies antirétrovirales ont été divisées en trois groupes (favorisant peu, moyennement et fortement la dyslipidémie), et trois scores génétiques ont été créés (profil favorable, moyennement favorable, non favorable/favorisant la dyslipidémie). Dans un premier temps, l'effet sur la valeur des lipides d'un ou deux allèles variants a été analysé au moyen d'un modèle de régression pour chaque SNP en ajustant le modèle pour les variables non- génétiques. Dans un deuxième temps, les SNP ayant une valeur p >= à 0.2 ont été repris dans un model Multi-SNP, ce modèle est également ajusté pour les variables non-génétiques. Puisque cette étude se base sur des SNP précédemment identifiés, celle-ci évalue uniquement l'association établie entre chaque SNP et les critères qui ont été établis au préalable, tels que : Cholestérol totale, HDL Cholestérol, non-HDL Cholestérol ou Triglycérides. Les résultats trouvés lors de |'étude confirment les résultats de la littérature. Cette étude montre que les SNP associés à la dyslipidémie doivent être analysés dans le contexte d'une thérapie antirétrovirale en tenant compte de la démographie et en considérant les valeurs du HIV (CD4+, virémie). Ces SNP montrent une tendance à prédire une dyslipidémie prolongée chez l'individu. En effet, un patient avec une thérapie antirétrovirale favorisant la dyslipidémie et un patrimoine génétique non-favorable a un risque qui est 3-f0is plus important d'avoir un Non-HDL- Cholestérol élevé, 5-fois plus important d'avoir un HDL-Cholestérol abaissé, et 4 à 5-fois plus important d'avoir une hypertriglycéridémie qu'un patient qui suit une thérapie antirétrovirale favorisant peu la dyslipidémie qui a un patrimoine génétique favorable. Vu la corrélation entre les SNP et la thérapie antirétrovirale, les cliniciens devraient intégrer les informations génétiques afin de choisir une thérapie antirétrovirale en fonction du patrimoine génétique.

Electronic and vibrational contributions to first hyperpolarizability of donor-acceptor-substituted azobenzene

In this study we report on the electronic and vibrational (hyper)polarizabilities of donor–acceptorsubstituted azobenzene. It is observed that both electronic and vibrational contributions to the electricdipole first hyperpolarizability of investigated photoactive molecule substantially depend on the conformation. The contributions to the nuclear relaxation first hyperpolarizability are found to be quite important in the case of two considered isomers (cis and trans). Although the double-harmonic term is found to be the largest in terms of magnitude, it is shown that the total value of the nuclear relaxation contribution to vibrational first hyperpolarizability is a result of subtle interplay of higher-order contributions. As a part of the study, we also assess the performance of long-range-corrected densityfunctional theory in determining vibrational contributions to electric dipole (hyper)polarizabilities. In most cases, the applied long-range-corrected exchange correlation potentials amend the drawbacks of their conventional counterparts

Tele-education and competencies assessment to Brazilian's auxiliary nurse

This paper presents Brazilian's experience with the organization of methods and strategies for the assessment of competencies for technical level of nursing workers. The evaluative process proposed includes the creation of a learning-oriented and distance-based virtual assessment environment. The proposed methodology for professional competencies assessment adopted a critical-emancipatory perspective. A tele-education environment was deployed, involving software development - a virtual man - and an assessment cybertutor. Learning modules for the cybertutor were developed and videos of clinical simulations, structured around assessment in cognitive, behavioral, and simulation areas. The evaluation modules considered aspects of competencies in know-know, know-how and know-act professional ethics. Also the variability of practices of nursing - hospitals and primary health care units - was considered. This instrument showed as an important strategy for the optimization of assessment procedures that are widely used across Brazil and it is a powerful tool for incorporation into the continuing professional education.

Neogene antecedents of the modern human hand and its relation to bipedalism

El present projecte s'ha dut a terme a l'American Museum of Natural History (AMNH, New York) entre el 31 de Desembre de 2010 i el 30 de Desembre de 2012. L'objectiu del projecte era elucidar la història evolutiva de la mà humana: traçar els canvis evolutius en la seva forma i proporcions que van propiciar la seva estructura moderna que permet als humans manipular amb precisió. El treball realitzat ha inclòs recol•lecció de dades i anàlisis, redacció de resultats i formació en mètodes analítics específics. Durant aquest temps, l'autor a completat la seva de base de dades existent en mesures lineals de la mà a hominoides. També s'han agafat dades del peu; d'aquesta forma ara mateix es compta amb una base de dades amb més de 500 individus, amb més de 200 mesures per cada un. També s'han agafat dades en tres imensions utilitzant un làser escàner. S'han après tècniques de morfometria geomètrica 3D directament dels pioners al camp a l'AMNH. Com a resultat d'aquesta feina s'han produït 10 resums (publicats a congressos internacionals) i 9 manuscrits (molts d'ells ja publicats a revistes internacionals) amb resultats de gran rellevància: La mà humana posseeix unes proporcions relativament primitives, que són més similars a les proporciones que tenien els hominoides fòssils del Miocè que no pas a la dels grans antropomorfs actuals. Els darrers tenen unes mans allargades amb un polzes molt curts que reflexen l'ús de la mà com a eina de suspensió sota les branques. En canvi, els hominoides del Miocè tenien unes mans relativament curtes amb un polze llarg que feien servir per estabilitzar el seu pes quan caminaven per sobre de les branques. Una vegada els primers homínids van aparèixer al final del Miocè (fa uns 6 Ma) i van començar a fer servir el bipedisme com a mitjà més comú de locomoció, les seves mans van ser "alliberades" de les seves funcions locomotores. La selecció natural—ara només treballant en la manipulació—va convertir les proporcions ja existents de la mà d'aquests primats en l'òrgan manipulatori que representa la mà humana avui dia.

Intermittent atrial tachycardia promotes repolarization alternans and conduction slowing during rapid rates, and increases susceptibility to atrial fibrillation in a free-behaving sheep model.

INTRODUCTION: Paroxysmal atrial fibrillation (AF) may be triggered by intermittent atrial tachycardia, and ultimately lead to persistent AF. However, the mechanisms by which intermittent atrial tachycardia promotes sustained AF are not well understood. METHODS AND RESULTS: Eight sheep were chronically implanted with 2 pacemakers for the recording of broadband right atrial unipolar electrograms, and for the delivery of electrophysiological stimulation protocols and intermittent right atrial tachycardia. Right atrial kinetics of activation recovery interval (ARI) as a surrogate for action potential duration, of conduction time and velocity, and of repolarization alternans were analyzed at incremental pacing rates during the remodeling process induced by weeks of intermittent atrial tachycardia until the development of sustained AF. Intermittent atrial tachycardia decreased ARI and blunted its rate adaptation, facilitated atrial capture, and slowed conduction at high rates, and increased susceptibility to pacing-induced AF. In spite of blunted ARI rate adaptation, right atrial repolarization alternans was maintained during remodeling, and further increased in magnitude just before rapid pacing-induced AF. CONCLUSION: This study suggests that weeks of intermittent right atrial tachycardia result in a gradual electrical remodeling favorable for wavebreaks and reentry that may facilitate fibrillation.

Combination of fluorescence microscopy and nanomotion detection to characterize bacteria.

Antibiotic-resistant pathogens are a major health concern in everyday clinical practice. Because their detection by conventional microbial techniques requires minimally 24 h, some of us have recently introduced a nanomechanical sensor, which can reveal motion at the nanoscale. By monitoring the fluctuations of the sensor, this technique can evidence the presence of bacteria and their susceptibility to antibiotics in less than 1 h. Their amplitude correlates to the metabolism of the bacteria and is a powerful tool to characterize these microorganisms at low densities. This technique is new and calls for an effort to optimize its protocol and determine its limits. Indeed, many questions remain unanswered, such as the detection limits or the correlation between the bacterial distribution on the sensor and the detection's output. In this work, we couple fluorescence microscopy to the nanomotion investigation to determine the optimal experimental protocols and to highlight the effect of the different bacterial distributions on the sensor.

Impaired fast-spiking, suppressed cortical inhibition and increased susceptibility to seizures in mice lacking Kv3.2 K+ channel proteins

Voltage-gated K+ channels of the Kv3 subfamily have unusual electrophysiological properties, including activation at very depolarized voltages (positive to −10 mV) and very fast deactivation rates, suggesting special roles in neuronal excitability. In the brain, Kv3 channels are prominently expressed in select neuronal populations, which include fast-spiking (FS) GABAergic interneurons of the neocortex, hippocampus, and caudate, as well as other high-frequency firing neurons. Although evidence points to a key role in high-frequency firing, a definitive understanding of the function of these channels has been hampered by a lack of selective pharmacological tools. We therefore generated mouse lines in which one of the Kv3 genes, Kv3.2, was disrupted by gene-targeting methods. Whole-cell electrophysiological recording showed that the ability to fire spikes at high frequencies was impaired in immunocytochemically identified FS interneurons of deep cortical layers (5-6) in which Kv3.2 proteins are normally prominent. No such impairment was found for FS neurons of superficial layers (2-4) in which Kv3.2 proteins are normally only weakly expressed. These data directly support the hypothesis that Kv3 channels are necessary for high-frequency firing. Moreover, we found that Kv3.2 −/− mice showed specific alterations in their cortical EEG patterns and an increased susceptibility to epileptic seizures consistent with an impairment of cortical inhibitory mechanisms. This implies that, rather than producing hyperexcitability of the inhibitory interneurons, Kv3.2 channel elimination suppresses their activity. These data suggest that normal cortical operations depend on the ability of inhibitory interneurons to generate high-frequency firing.

Pédiatrie [Current progress in pediatrics: obesity and diagnosis approach to the febrile child]

The literature shows that obesity is a public health problem concerning especially the general paediatrician. While prevention has probably more chances of success than treatment, drugs or, in case of failure, the surgical approach are reserved for extreme cases. In the domain of infectiology the different laboratory tests allow only partially to diagnose severe infections. But in the context of a potential influenza pandemic rapid virologic tests become more and more important. They allow a more precise diagnosis and a reduction of hospitalisations and of antibiotic prescriptions. A review of the north American experience with the pneumococal vaccine shows that the heptavalent vaccine will change our approach in infants with fever in whom we suspect a severe infection.

Regulation of stress response is heritable and functionally linked to melanin-based coloration.

Abstract Sexual selection theory posits that ornaments can signal the genetic quality of an individual. Eumelanin-based coloration is such an ornament and can signal the ability to cope with a physiological stress response because the melanocortin system regulates eumelanogenesis as well as physiological stress responses. In the present article, we experimentally investigated whether the stronger stress sensitivity of light than dark eumelanic individuals stems from differential regulation of stress hormones. Our study shows that darker eumelanic barn owl nestlings have a lower corticosterone release after a stressful event, an association, which was also inherited from the mother (but not the father) to the offspring. Additionally, nestlings sired by darker eumelanic mothers more quickly reduced experimentally elevated corticosterone levels. This provides a solution as to how ornamented individuals can be more resistant to various sources of stress than drab conspecifics. Our study suggests that eumelanin-based coloration can be a sexually selected signal of resistance to stressful events.

Development of a new chlamydiales-specific real-time PCR and its application to respiratory clinical samples.

Originally composed of the single family Chlamydiaceae, the Chlamydiales order has extended considerably over the last several decades. Chlamydia-related bacteria were added and classified into six different families and family-level lineages: the Criblamydiaceae, Parachlamydiaceae, Piscichlamydiaceae, Rhabdochlamydiaceae, Simkaniaceae, and Waddliaceae. While several members of the Chlamydiaceae family are known pathogens, recent studies showed diverse associations of Chlamydia-related bacteria with human and animal infections. Some of these latter bacteria might be of medical importance since, given their ability to replicate in free-living amoebae, they may also replicate efficiently in other phagocytic cells, including cells of the innate immune system. Thus, a new Chlamydiales-specific real-time PCR targeting the conserved 16S rRNA gene was developed. This new molecular tool can detect at least five DNA copies and show very high specificity without cross-amplification from other bacterial clade DNA. The new PCR was validated with 128 clinical samples positive or negative for Chlamydia trachomatis or C. pneumoniae. Of 65 positive samples, 61 (93.8%) were found to be positive with the new PCR. The four discordant samples, retested with the original test, were determined to be negative or below detection limits. Then, the new PCR was applied to 422 nasopharyngeal swabs taken from children with or without pneumonia; a total of 48 (11.4%) samples were determined to be positive, and 45 of these were successfully sequenced. The majority of the sequences corresponded to Chlamydia-related bacteria and especially to members of the Parachlamydiaceae family.

Deletion of the RNA-binding proteins ZFP36L1 and ZFP36L2 leads to perturbed thymic development and T lymphoblastic leukemia.

ZFP36L1 and ZFP36L2 are RNA-binding proteins (RBPs) that interact with AU-rich elements in the 3' untranslated region of mRNA, which leads to mRNA degradation and translational repression. Here we show that mice that lacked ZFP36L1 and ZFP36L2 during thymopoiesis developed a T cell acute lymphoblastic leukemia (T-ALL) dependent on the oncogenic transcription factor Notch1. Before the onset of T-ALL, thymic development was perturbed, with accumulation of cells that had passed through the beta-selection checkpoint without first expressing the T cell antigen receptor beta-chain (TCRbeta). Notch1 expression was higher in untransformed thymocytes in the absence of ZFP36L1 and ZFP36L2. Both RBPs interacted with evolutionarily conserved AU-rich elements in the 3' untranslated region of Notch1 and suppressed its expression. Our data establish a role for ZFP36L1 and ZFP36L2 during thymocyte development and in the prevention of malignant transformation.

Predictability of music descriptor time series and its application to cover song detection

Intuitively, music has both predictable and unpredictable components. In this work we assess this qualitative statement in a quantitative way using common time series models fitted to state-of-the-art music descriptors. These descriptors cover different musical facets and are extracted from a large collection of real audio recordings comprising a variety of musical genres. Our findings show that music descriptor time series exhibit a certain predictability not only for short time intervals, but also for mid-term and relatively long intervals. This fact is observed independently of the descriptor, musical facet and time series model we consider. Moreover, we show that our findings are not only of theoretical relevance but can also have practical impact. To this end we demonstrate that music predictability at relatively long time intervals can be exploited in a real-world application, namely the automatic identification of cover songs (i.e. different renditions or versions of the same musical piece). Importantly, this prediction strategy yields a parameter-free approach for cover song identification that is substantially faster, allows for reduced computational storage and still maintains highly competitive accuracies when compared to state-of-the-art systems.