Spatial modules of coherent activity in pathway-specific LFPs in the hippocampus reflect topology and different modes of presynaptic synchronization.

Ongoing network activity often manifests as irregular fluctuations in local field potentials (LFPs), a complex mixture of multicellular synaptic currents of varying locations and extensions. Among other conditions, for synchronously firing presynaptic units to generate sizable postsynaptic LFPs, their axonal territories should overlap. We have taken advantage of anatomical regularity of the rat hippocampus and combined multiple linear recordings and spatial discrimination techniques to separate pathway-specific LFPs with enough spatial resolution to discriminate postsynaptic regions of varying activation, and to investigate their presynaptic origin, chemical nature, and spatial extension. We identified 6 main excitatory and inhibitory LFP generators with different synaptic territories in principal cells and hippocampal subfields matching anatomical pathways. Some recognized pathways did not contribute notably to LFPs. Each showed different septo-temporal spatial modules over which the field potential fluctuations were synchronous. These modules were explained by either the strong overlap of synaptic territories of coactivated afferent neurons (e.g., CA3 clusters for CA1 Schaffer LFPs), or widespread coalescence of postsynaptic territories (granule cell somatic inhibition). We also show evidence that distinct modes of afferent synchronization generate stereotyped spatial patterns of synchronous LFPs in one pathway. Thus, studying spatial coherence of pathway-specific LFPs provides remote access to the dynamics of afferent populations.

Targeting ribosome biogenesis reinforces ERK-dependent senescence in pancreatic cancer.

Pancreatic adenocarcinomas (PDAC) often possess mutations in K-Ras that stimulate the ERK pathway. Aberrantly high ERK activation triggers oncogene-induced senescence, which halts tumor progression. Here we report that low-grade pancreatic intraepithelial neoplasia displays very high levels of phospho-ERK consistent with a senescence response. However, advanced lesions that have circumvented the senescence barrier exhibit lower phospho-ERK levels. Restoring ERK hyperactivation in PDAC using activated RAF leads to ERK-dependent growth arrest with senescence biomarkers. ERK-dependent senescence in PDAC was characterized by a nucleolar stress response including a selective depletion of nucleolar phosphoproteins and intranucleolar foci containing RNA polymerase I designated as senescence-associated nucleolar foci (SANF). Accordingly, combining ribosome biogenesis inhibitors with ERK hyperactivation reinforced the senescence response in PDAC cells. Notably, comparable mechanisms were observed upon treatment with the platinum-based chemotherapy regimen FOLFIRINOX, currently a first-line treatment option for PDAC. We thus suggest that drugs targeting ribosome biogenesis can improve the senescence anticancer response in pancreatic cancer.

Does a critical hemodynamic situation develop from right ventriculotomy and free wall infarct or from small changes in dysfunctional right ventricle afterload?

An experimental model for right ventricle free wall infarct associated with double ventriculotomy and tricuspid insufficiency was created to evaluate whether right ventricle failure can cause profound refractory heart failure or whether modifications in right ventricular afterload are more influential in this regard. In our model, the left ventricle, interventricular septum and right atrial wall were maintained intact and pulmonary banding made it possible to modify right ventricular afterload during the experiment. The results of our study showed that pure right ventricular failure does affect the hemodynamic state negatively, but it is not itself, a cause of death in dogs. A slight increase in the dysfunctional right ventricular afterload produced a profound deterioration in the hemodynamic state that required pulmonary artery debanding within no more than 10 minutes.

[Thyroid function alterations in children with congenital cardiac disease after catheterization with iodinated contrast agents]. / Alteraciones de la función tiroidea en niños con cardiopatía congénita tras la realización de cateterismo con contrastes yodados.

INTRODUCTION AND OBJECTIVES: Iodinated contrast agents can block thyroid hormone synthesis. The aims of this study were: 1st) to study the incidence of thyroid function disturbances in children with congenital heart disease after cardiac catheterization, 2nd) to analyze the predisposing factors that may lead to the development of hypothyroidism after angiography, and 3rd) to determine the duration of these hypothyroidism states. PATIENTS AND METHODS: From february 1993 to April 1997 thyrotropine (TSH) and free thyroxine (FT4) serum values were analyzed before cardiac catheterization and in the two following weeks, in 99 children under three years of age, with congenital cardiac disease. Those patients who showed any postangiography increase in TSH were further evaluated by weekly measures of serum thyroid hormones and TSH until normal values were obtained or until the initiation of hormonal replacement therapy. The patients' data (age, previous exposure to contrast agents, cardiac disease, associated extracardiac malformations, renal failure, severity of illness, treatment) and the catheterism data (the dose and type of contrast and the fluoroscopy time) were included in the univariant analysis. RESULTS: 10 mUI/ml), that persisted beyond three weeks in six cases. The occurrence of multiple malformation syndromes was the most clearly associated risk factor (p < 0,01) not only in the development of postangiography hypothyroidism but also in longer hormonal dysfunction. CONCLUSIONS: Thyroid function should be tested in every patient with multiple malformation syndrome that undergo angiocardiography with iodinated contrast agents.

[Percutaneous closure of atrial septal defect with the Amplatz device: initial result and mid-term follow-up]. / Cierre percutáneo de la comunicación interauricular mediante dispositivo de Amplatz: resultado inicial y seguimiento a medio plazo.

OBJECTIVES: Percutaneous device occlusion of atrial septal defects (ASD) is, although with some limitations, an alternative to surgical closure. The aim of this study was to evaluate the efficacy and safety of percutaneous ASD closure using the Amplatz device. PATIENTS AND METHODS: From October 1999 to March 2000, 25 children underwent transcatheter closure of ASD at a mean +/- SD age of 8.7 +/- 3.1 years (range 3-15 years) and a mean weight of 31.8 +/- 16.7 kg (range 11-84 kg). Device selection was based on the stretched diameter of the ASD using the PTA OS balloon. The device was implanted under ultrasonographic and radiological guidance. All patients showed signs of volume-overload of the right ventricle. The ASD was single (n = 21), with two separate holes (n = 2), or cribiform (n = 2). RESULTS: The median +/- SD size of the device used was 21.7 +/- 5.4 mm (range 15-36 mm). In twenty-two patients (88%) the device was successfully implanted. A repeat echocardiogram was performed the next day before discharge. Two patients underwent surgery after deployment of the device due to mitral valve dysfunction (n = 1) or residual leak (n = 1). In a patient with a two-hole ASD, another device was percutaneously withdrawn, while still attached to the delivery cable due to incomplete occlusion. CONCLUSION: a) Transcatheter occlusion with the Amplatzer device is an effective treatment for ostium secundum atrial septal defects; b) the low complication rate and the short hospitalization period makes this procedure the treatment of choice in these patients, and c) ASD which are too large, cribiform or with deficient rims may require a different approach.