Screening for elevated blood pressure in children and adolescents: a critical appraisal.

Although screening for elevated blood pressure (BP) in adults is beneficial, evidence of its beneficial effects in children is not clear. Elevated BP in children is associated with atherosclerosis early in life and tracks across the life course. However, because of the high variability in BP, tracking is weak, and having an elevated BP in childhood has a low predictive value for having elevated BP later in life. The absolute risk of cardiovascular diseases associated with a given level of BP in childhood and the long-term effect of treatment beginning in childhood are not known. No study has experimentally evaluated the benefits and harm of BP screening in children. One modeling study indicates that BP screen-and-treat strategies in adolescents are moderately cost-effective but less cost-effective than population-wide interventions to decrease BP for the reduction of coronary heart diseases. The US National Heart, Lung, and Blood Institute and the European Society of Hypertension recommend that children 3 years of age and older have their BP measured during every health care visit. According to the US Preventive Services Task Force, there is no sufficient evidence to recommend for or against screening, but their recommendations have to be updated. Whether the benefits of universal BP screening in children outweigh the harm has to be determined. Studies are needed to assess the absolute risk of cardiovascular diseases associated with elevated BP in childhood, to evaluate how to simplify the identification of elevated BP, to evaluate the long-term benefits and harm of treatment beginning in childhood, and to compare universal and targeted screening strategies.

Les itinéraires cliniques sont-ils efficaces ? : revue Cochrane pour le praticien

Cet article présente les résultats de la revue systématique: Rotter T, Kinsman L, James E, et al. Clinical pathways : Effects on professional practice, patient outcomes, length of stay and hospital costs. Cochrane Database of Systematic Reviews 2010, Issue 3. Art. No:CD006632. DOI:10.1002/14651858.CD006632.pub2. PMID: 20238347.

The nuclear matrix: a critical appraisal.

It is becoming increasingly clear that the cell nucleus is a highly structurized organelle. Because of its tight compartmentalization, it is generally believed that a framework must exist, responsible for maintaining such a spatial organization. Over the last twenty years many investigations have been devoted to identifying the nuclear framework. Structures isolated by different techniques have been obtained in vitro and are variously referred to as nuclear matrix, nucleoskeleton or nuclear scaffold. Many different functions, such as DNA replication and repair, mRNA transcription, processing and transport have been described to occur in close association with these structures. However, there is still much debate as to whether or not any of these preparations corresponds to a nuclear framework that exists in vivo. In this article we summarize the most commonly-used methods for obtaining preparations of nuclear frameworks and we also stress the possible artifacts that can be created in vitro during the isolation procedures. Emphasis is placed also on the protein composition of the frameworks as well as on some possible signalling functions that have been recently described to occur in tight association with the nuclear matrix.

T cell receptor specificity is critical for the development of epidermal gammadelta T cells.

A particular feature of gammadelta T cell biology is that cells expressing T cell receptor (TCR) using specific Vgamma/Vdelta segments are localized in distinct epithelial sites, e.g., in mouse epidermis nearly all gammadelta T cells express Vgamma3/Vdelta1. These cells, referred to as dendritic epidermal T cells (DETC) originate from fetal Vgamma3+ thymocytes. The role of gammadelta TCR specificity in DETC's migration/localization to the skin has remained controversial. To address this issue we have generated transgenic (Tg) mice expressing a TCR delta chain (Vdelta6.3-Ddelta1-Ddelta2-Jdelta1-Cdelta), which can pair with Vgamma3 in fetal thymocytes but is not normally expressed by DETC. In wild-type (wt) Vdelta6.3Tg mice DETC were present and virtually all of them express Vdelta6.3. However, DETC were absent in TCR-delta(-/-) Vdelta6.3Tg mice, despite the fact that Vdelta6.3Tg gammadelta T cells were present in normal numbers in other lymphoid and nonlymphoid tissues. In wt Vdelta6.3Tg mice, a high proportion of in-frame Vdelta1 transcripts were found in DETC, suggesting that the expression of an endogenous TCR-delta (most probably Vdelta1) was required for the development of Vdelta6.3+ epidermal gammadelta T cells. Collectively our data demonstrate that TCR specificity is essential for the development of gammadelta T cells in the epidermis. Moreover, they show that the TCR-delta locus is not allelically excluded.

Art. "Gütergemeinschaft"

(Résumé de l'ouvrage) Die RGG4 bietet in 15 665 Artikeln und Teilartikeln einen fundierten Überblick über Religion und Religionen, wie sie gelebt und gedacht wurden und werden. Sie bietet den neuesten Forschungsstand, dargestellt von 3 972 ausgewiesenen Kennern der jeweiligen Materie aus 74 Ländern. Die RGG4 führt die Tradition der ersten drei Auflagen fort: Aus der Mitte des evangelischen Glaubens ist weit mehr als die Theologie im Blick, nach deren Kriterien wird aber gewichtet.Die RGG4 erschließt die Themen in Form von biographischen Artikeln, Länder-, Orts-, Begriffs- und Ereignisartikeln sowie Artikeln über Gruppierungen und Institutionen. Knappe Definitionsartikel und Querverweise erleichtern die schnelle Information. Ausführliche Reihenartikel behandeln Stichworte wie "Abendmahl" oder "Christentum" aus vielerlei Perspektiven. Die RGG4 ist durch die Artikelvielfalt und die detailgenaue Darstellung ein Nachschlagewerk; zugleich ist sie eine Lehr- und Repetitionsbibliothek. Sie bringt mit einem ausgesucht lesbaren Schriftbild ein Maximum an Information auf einer Seite. Die acht Bände der RGG4 decken jeweils ganze Buchstaben ab. Der das Werk abschließende Registerband ermöglicht den Zugang zu dem in der RGG4 enthaltenen Wissen nach noch spezielleren Fragestellungen wie beispielsweise Namen und Stichworten, die keinen Haupteintrag haben. Selbstverständlich ist die RGG4 auf alterungsbeständigem Papier gedruckt, solide fadengeheftet und in Buckramleinen gebunden. Die RGG4 erhielt von der Stiftung Buchkunst die Auszeichnung "Eines der schönsten Bücher 1998. Vorbildlich gestaltet in Satz, Druck, Bild und Einband."

Art. "Hellenisten"

(Résumé de l'ouvrage) Die RGG4 bietet in 15 665 Artikeln und Teilartikeln einen fundierten Überblick über Religion und Religionen, wie sie gelebt und gedacht wurden und werden. Sie bietet den neuesten Forschungsstand, dargestellt von 3 972 ausgewiesenen Kennern der jeweiligen Materie aus 74 Ländern. Die RGG4 führt die Tradition der ersten drei Auflagen fort: Aus der Mitte des evangelischen Glaubens ist weit mehr als die Theologie im Blick, nach deren Kriterien wird aber gewichtet.Die RGG4 erschließt die Themen in Form von biographischen Artikeln, Länder-, Orts-, Begriffs- und Ereignisartikeln sowie Artikeln über Gruppierungen und Institutionen. Knappe Definitionsartikel und Querverweise erleichtern die schnelle Information. Ausführliche Reihenartikel behandeln Stichworte wie "Abendmahl" oder "Christentum" aus vielerlei Perspektiven. Die RGG4 ist durch die Artikelvielfalt und die detailgenaue Darstellung ein Nachschlagewerk; zugleich ist sie eine Lehr- und Repetitionsbibliothek. Sie bringt mit einem ausgesucht lesbaren Schriftbild ein Maximum an Information auf einer Seite. Die acht Bände der RGG4 decken jeweils ganze Buchstaben ab. Der das Werk abschließende Registerband ermöglicht den Zugang zu dem in der RGG4 enthaltenen Wissen nach noch spezielleren Fragestellungen wie beispielsweise Namen und Stichworten, die keinen Haupteintrag haben. Selbstverständlich ist die RGG4 auf alterungsbeständigem Papier gedruckt, solide fadengeheftet und in Buckramleinen gebunden. Die RGG4 erhielt von der Stiftung Buchkunst die Auszeichnung "Eines der schönsten Bücher 1998. Vorbildlich gestaltet in Satz, Druck, Bild und Einband."

Dynamic visual information plays a critical role for spatial navigation in water but not on solid ground.

In the Morris water maze (MWM) task, proprioceptive information is likely to have a poor accuracy due to movement inertia. Hence, in this condition, dynamic visual information providing information on linear and angular acceleration would play a critical role in spatial navigation. To investigate this assumption we compared rat's spatial performance in the MWM and in the homing hole board (HB) tasks using a 1.5 Hz stroboscopic illumination. In the MWM, rats trained in the stroboscopic condition needed more time than those trained in a continuous light condition to reach the hidden platform. They expressed also little accuracy during the probe trial. In the HB task, in contrast, place learning remained unaffected by the stroboscopic light condition. The deficit in the MWM was thus complete, affecting both escape latency and discrimination of the reinforced area, and was thus task specific. This dissociation confirms that dynamic visual information is crucial to spatial navigation in the MWM whereas spatial navigation on solid ground is mediated by a multisensory integration, and thus less dependent on visual information.

Bcl9/Bcl9l are critical for Wnt-mediated regulation of stem cell traits in colon epithelium and adenocarcinomas.

Canonical Wnt signaling plays a critical role in stem cell maintenance in epithelial homeostasis and carcinogenesis. Here, we show that in the mouse this role is critically mediated by Bcl9/Bcl9l, the mammalian homologues of Legless, which in Drosophila is required for Armadillo/beta-catenin signaling. Conditional ablation of Bcl9/Bcl9l in the intestinal epithelium, where the essential role of Wnt signaling in epithelial homeostasis and stem cell maintenance is well documented, resulted in decreased expression of intestinal stem cell markers and impaired regeneration of ulcerated colon epithelium. Adenocarcinomas with aberrant Wnt signaling arose with similar incidence in wild-type and mutant mice. However, transcriptional profiles were vastly different: Whereas wild-type tumors displayed characteristics of epithelial-mesenchymal transition (EMT) and stem cell-like properties, these properties were largely abrogated in mutant tumors. These findings reveal an essential role for Bcl9/Bcl9l in regulating a subset of Wnt target genes involved in controlling EMT and stem cell-related features and suggest that targeting the Bcl9/Bcl9l arm of Wnt signaling in Wnt-activated cancers might attenuate these traits, which are associated with tumor invasion, metastasis, and resistance to therapy.

Macrophage migration inhibitory factor: a counter-regulator of glucocorticoid action and critical mediator of septic shock.

Recent studies have led to the discovery of a mediator that acts as an endogenous counter-regulator of glucocorticoid action within the immune system. Isolated as a product of anterior pituitary cells, this protein was found to have the sequence of macrophage migration inhibitory factor (MIF), one of the first cytokine activities to be described. Macrophages and T cells release MIF in response both to various inflammatory stimuli and upon incubation with low concentrations of glucocorticoids. The glucocorticoid-induced secretion of MIF is tightly regulated and decreases at high, anti-inflammatory steroid concentrations. Once secreted, MIF "overrides" the anti-inflammatory and immunosuppressive effects of steroids on macrophage and T-cell cytokine production. The physiological role of MIF thus appears to be to counter-balance steroid inhibition of the inflammatory response. Anti-MIF antibodies fully protect animals from experimentally induced gram-negative or gram-positive septic shock, an effect that may be the result of the increased anti-inflammatory effects of glucocorticoids after neutralization of endogenous MIF. Anti-MIF therapeutic strategies are presently under development and may prove to be a means to modulate cytokine production in septic shock as well as in other inflammatory disease states.

Maintien des capacités des myopathes ou l'art de prescrire l'exercice physique [How to maintain the motor capacities in neuromuscular disorders or the art to prescribe physical exercises].

Optimum management of non-acquired neuromuscular disorders requires a multidisciplinary approach in order to prevent secondary complications related to the progression of the disease and to maintain the patient's independency in daily activities. For treatments, the physiotherapists and occupational therapists must have precise and measurable goals to quantify muscle strength and functions in conjunction with a specialist in neurorehabilitation. Examples of simple motor scores or scales are given in order to transmit precise information to the GP and the multidisciplinary team, and type of orthosis and physiotherapy programmes are given as pieces of advice to assume the follow-up of patients.

CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-kappa B activation.

CARMA1 is a lymphocyte-specific member of the membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins, which coordinate signaling pathways emanating from the plasma membrane. CARMA1 interacts with Bcl10 via its caspase-recruitment domain (CARD). Here we investigated the role of CARMA1 in T cell activation and found that T cell receptor (TCR) stimulation induced a physical association of CARMA1 with the TCR and Bcl10. We found that CARMA1 was constitutively associated with lipid rafts, whereas cytoplasmic Bcl10 translocated into lipid rafts upon TCR engagement. A CARMA1 mutant, defective for Bcl10 binding, had a dominant-negative (DN) effect on TCR-induced NF-kappa B activation and IL-2 production and on the c-Jun NH(2)-terminal kinase (Jnk) pathway when the TCR was coengaged with CD28. Together, our data show that CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-kappa B activation and CD28 costimulation-dependent Jnk activation.