Tuberculosis in otherwise healthy adults with inherited TNF deficiency.

Severe defects in human IFNγ immunity predispose individuals to both Bacillus Calmette-Guérin disease and tuberculosis, whereas milder defects predispose only to tuberculosis1. Here we report two adults with recurrent pulmonary tuberculosis who are homozygous for a private loss-of-function TNF variant. Neither has any other clinical phenotype and both mount normal clinical and biological inflammatory responses. Their leukocytes, including monocytes and monocyte-derived macrophages (MDMs) do not produce TNF, even after stimulation with IFNγ. Blood leukocyte subset development is normal in these patients. However, an impairment in the respiratory burst was observed in granulocyte-macrophage colony-stimulating factor (GM-CSF)-matured MDMs and alveolar macrophage-like (AML) cells2 from both patients with TNF deficiency, TNF- or TNFR1-deficient induced pluripotent stem (iPS)-cell-derived GM-CSF-matured macrophages, and healthy control MDMs and AML cells differentiated with TNF blockers in vitro, and in lung macrophages treated with TNF blockers ex vivo. The stimulation of TNF-deficient iPS-cell-derived macrophages with TNF rescued the respiratory burst. These findings contrast with those for patients with inherited complete deficiency of the respiratory burst across all phagocytes, who are prone to multiple infections, including both Bacillus Calmette-Guérin disease and tuberculosis3. Human TNF is required for respiratory-burst-dependent immunity to Mycobacterium tuberculosis in macrophages but is surprisingly redundant otherwise, including for inflammation and immunity to weakly virulent mycobacteria and many other infectious agents.

Temporal exponential random graph models of longitudinal brain networks after stroke.

Plasticity after stroke is a complex phenomenon. Functional reorganization occurs not only in the perilesional tissue but throughout the brain. However, the local connection mechanisms generating such global network changes remain largely unknown. To address this question, time must be considered as a formal variable of the problem rather than a simple repeated observation. Here, we hypothesized that the presence of temporal connection motifs, such as the formation of temporal triangles (T) and edges (E) over time, would explain large-scale brain reorganization after stroke. To test our hypothesis, we adopted a statistical framework based on temporal exponential random graph models (tERGMs), where the aforementioned temporal motifs were implemented as parameters and adapted to capture global network changes after stroke. We first validated the performance on synthetic time-varying networks as compared to standard static approaches. Then, using real functional brain networks, we showed that estimates of tERGM parameters were sufficient to reproduce brain network changes from 2 weeks to 1 year after stroke. These temporal connection signatures, reflecting within-hemisphere segregation (T) and between hemisphere integration (E), were associated with patients' future behaviour. In particular, interhemispheric temporal edges significantly correlated with the chronic language and visual outcome in subcortical and cortical stroke, respectively. Our results indicate the importance of time-varying connection properties when modelling dynamic complex systems and provide fresh insights into modelling of brain network mechanisms after stroke.

Effects of a Physical Activity Program Potentiated with ICTs on the Formation and Dissolution of Friendship Networks of Children in a Middle-Income Country.

This paper assesses the potential cohesion effect of a physical activity (PA) school-based intervention potentiated using text messages (SMS) through analyzing longitudinally the friendship network structure and the mechanisms of the formation and dissolution of friendships. Three schools (n = 125 participants) in Bogotá, Colombia, were randomly assigned into three groups: Modulo Activo Recreo Activo (MARA) + SMS (networks 1 and 2), MARA (networks 3 and 4), and control (no intervention: networks 5-7). We collected socio-economic, health-related, network structure, and intervention satisfaction variables in the baseline and after 10 weeks on July-November 2013. For each classroom network, we conducted four models using a temporal and static network approach to assess (1) temporal social network changes, (2) friendship homophily, (3) friendship formation and dissolution mechanisms, and (4) effect of SMS on the networks' cohesion. We found that (1) social cohesion emerged in the four intervened networks that were measured over time with transitivity and homophily driven by clustering, (2) the intervention affected the mechanisms of friendship formation and dissolution, and (3) MARA + SMS on average created more social cohesion and 3.8 more friendships than the program alone. Potentially, school-based interventions with information and communication technologies (ICT) such as MARA + SMS could encourage social cohesion among children. The particular characteristics of each school network need to be considered when developing school-based interventions.

Molecular and epidemiologic findings of childhood acute leukemia in Costa Rica.

In Central America, nearly 70% of pediatric cancer is related to hemato-oncologic disorders, especially acute lymphoblastic leukemia (ALL). Preliminary studies have described a high incidence of childhood leukemia in these countries; however, no molecular analyses of these malignancies have yet been carried out. We studied diagnostic samples from 84 patients from the National Children's Hospital in San Jose, Costa Rica (65 precursor B-ALL, 5 T-cell ALL, and 14 acute myeloblastic leukemia). Our methodology included cytogenetic, fluorescent in situ hybridization, and polymerase chain reaction approaches. The observed rate of leukemia was 52.2 cases per million children per year. Twelve out of 65 (18.4%) precursor B-ALL tested positive for TEL-AML1 and 3 cases for BCR-ABL (4.6%). In addition, we detected 2 patients carrying an E2A-PBX1 transcript (3.1%) and 1 patient with an MLL-AF4 fusion gene (1.5%). None of the T-cell ALL cases were positive for either SIL-TAL1 or HOX11L2. Within 14 acute myeloblastic leukemia patients, we confirmed 2 cases with FLT3-internal tandem duplication+, 1 patient with AML1-ETO, and only 1 case carrying a PML-RARalpha rearrangement. The present study confirms the relatively high incidence of pediatric leukemia in Costa Rica and constitutes the first report regarding the incidence of the main molecular alterations of childhood leukemia in our region.

A statistical model for brain networks inferred from large-scale electrophysiological signals.

Network science has been extensively developed to characterize the structural properties of complex systems, including brain networks inferred from neuroimaging data. As a result of the inference process, networks estimated from experimentally obtained biological data represent one instance of a larger number of realizations with similar intrinsic topology. A modelling approach is therefore needed to support statistical inference on the bottom-up local connectivity mechanisms influencing the formation of the estimated brain networks. Here, we adopted a statistical model based on exponential random graph models (ERGMs) to reproduce brain networks, or connectomes, estimated by spectral coherence between high-density electroencephalographic (EEG) signals. ERGMs are made up by different local graph metrics, whereas the parameters weight the respective contribution in explaining the observed network. We validated this approach in a dataset of N = 108 healthy subjects during eyes-open (EO) and eyes-closed (EC) resting-state conditions. Results showed that the tendency to form triangles and stars, reflecting clustering and node centrality, better explained the global properties of the EEG connectomes than other combinations of graph metrics. In particular, the synthetic networks generated by this model configuration replicated the characteristic differences found in real brain networks, with EO eliciting significantly higher segregation in the alpha frequency band (8-13 Hz) than EC. Furthermore, the fitted ERGM parameter values provided complementary information showing that clustering connections are significantly more represented from EC to EO in the alpha range, but also in the beta band (14-29 Hz), which is known to play a crucial role in cortical processing of visual input and externally oriented attention. Taken together, these findings support the current view of the functional segregation and integration of the brain in terms of modules and hubs, and provide a statistical approach to extract new information on the (re)organizational mechanisms in healthy and diseased brains.

Incidencia de pruebas serológicas positivas banco de sangre, Hospital Nacional de Niños 2003-2004 / Incidence of serological tests positive blood bank National Hospital for Children 2003-2004

El estudio de la incidencia y del tipo de serología positiva que provoca el rechazo de los donadores de hemo componentes, constituye una pieza fundamental en el proceso de aseguramiento de calidad en un Banco de Sangre. Basado en esta necesidad, se evaluaron los distintos motivos de rechazo de personas donantes de sangre, haciendo énfasis en el descarte por serología positiva. De los cuatro mil individuos que se atendieron en promedio en la última década, se rechazaron cerca de un 20 por ciento, siendo las serologías positivas las responsables de una cuarta parte de estos rechazos. La mayor problemática ha pasado de ser las pruebas positivas de Chagas y VDRL, a los distintos marcadores de hepatitis B y C, especialmente los anticuerpos anti-HBcore. En el período 2003-2004, los portadores crónicos de hepatitis B constituyeron la mayoría de exámenes positivos, con una incidencia del 1.8 por ciento. Si se comparan los datos obtenidos en el presente reporte con estudios similares realizados en países como Estados Unidos y Argentina, encontramos una baja incidencia de serologías positivas.

Sistema Vitek vs E-test comparación de la susceptibilidad en cepas de Enterococcus spp / System Vitec versus E-test comparasion of the susceptibiity in stocks of Enterococcus spp

En un periodo de ocho meses, se aislaron 48 cepas de Enterococcus spp. las que se emplearon para realizar una comparación entre la susceptibilidad realizada usando el sistema automatizado Vitek de la casa BioMerieux y el método manual. E-test de la casa ABBiodisk. Los resultados obtenidos muestran una buena corelación entre ambos métodos, por lo que se sugiere utilizar el sistema Vitek en forma rutinaria y recurrir al método. E-test en casos de duda o como confirmación de resistencia a la hora de escoger la mejor opción terapéutica.