A novel dominant mutation of the Nav1.4 alpha-subunit domain I leading to sodium channel myotonia.

BACKGROUND: Mutations in SCN4A may lead to myotonia. METHODS: Presentation of a large family with myotonia, including molecular studies and patch clamp experiments using human embryonic kidney 293 cells expressing wild-type and mutated channels. RESULTS: In a large family with historic data on seven generations and a clear phenotype, including myotonia at movement onset, with worsening by cold temperature, pregnancy, mental stress, and especially after rest after intense physical activity, but without weakness, the phenotype was linked with the muscle sodium channel gene (SCN4A) locus, in which a novel p.I141V mutation was found. This modification is located within the first transmembrane segment of domain I of the Na(v)1.4 alpha subunit, a region where no mutation has been reported so far. Patch clamp experiments revealed a mutation-induced hyperpolarizing shift (-12.9 mV) of the voltage dependence of activation, leading to a significant increase (approximately twofold) of the window current amplitude. In addition, the mutation shifted the voltage dependence of slow inactivation by -8.7 mV and accelerated the entry to this state. CONCLUSIONS: We propose that the gain-of-function alteration in activation leads to the observed myotonic phenotype, whereas the enhanced slow inactivation may prevent depolarization-induced paralysis.

Semi-purity of tempered Deligne cohomology

In this paper we define the formal and tempered Deligne cohomology groups, that are obtained by applying the Deligne complex functor to the complexes of formal differential forms and tempered currents respectively. We then prove the existence of a duality between them, a vanishing theorem for the former and a semipurity property for the latter. The motivation of these results comes from the study of covariant arithmetic Chow groups. The semipurity property of tempered Deligne cohomology implies, in particular, that several definitions of covariant arithmetic Chow groups agree for projective arithmetic varieties.

Dynamically generated open-charm baryons beyond the zero-range approximation

The interaction of the low-lying pseudoscalar mesons with the ground-state baryons in the charm sector is studied within a coupled-channel approach using a t-channel vector-exchange driving force. The amplitudes describing the scattering of the pseudoscalar mesons off the ground-state baryons are obtained by solving the Lippmann-Schwinger equation. We analyze in detail the effects of going beyond the t=0 approximation. Our model predicts the dynamical generation of several open-charm baryon resonances in different isospin and strangeness channels, some of which can be clearly identified with recently observed states.

Proceso de construcción identitaria del pedagogo universitario en México

En este artículo presento algunos resultados de la investigación El pedagogo y su identidad profesional: el caso de los egresados de la carrera de Pedagogía de la Universidad Nacional Autónoma de México (Unam) y de la Universidad Veracruzana (UV)¹. Ella tuvo como objetivo dar cuenta de los procesos de constitución identitaria de los pedagogos egresados de estas universidades en las décadas de 1950, 1970 y 1990, según los planes de estudio por los que se formaram, y, concomitantemente, destacar los rasgos que han definido su identidad. La pregunta central que ha conducido todo el trabajo fue: ¿Cuáles son los rasgos que han ido constituyendo la identidad de los pedagogos de la Unam y de la UV, y, en función de esto, de qué identidad de pedagogo hablamos? Luego de entrevistar a 12 pedagogos (seis por institución, dos por generación), analizar sus testimonios y documentos tales como planes de estudio, publicaciones, etcétera, y poniéndolos a jugar con el referente teórico y las preguntas de investigación, puedo decir que la identidad del pedagogo se ha constituido como una identidad histórica, relacional e híbrida: es un tipo de profesional que cumple funciones diversas pero todas ellas vinculadas a algún ámbito de la educación en general (formal, no formal e informal) y las encara de manera distinta a la de otras profesiones que también se ocupan de la educación.

Pela integração da inteligência competitiva nos Enterprise Information Systems (EIS)

O objetivo deste artigo é evidenciar a importância da integração de um módulo de inteligência competitiva (coleta, organização e difusão da informação externa) nos sistemas de informações para o apoio à decisão das empresas, enriquecendo assim os Enterprise Information Systems (EIS). É a efetividade do gerente na busca da identificação ou da antecipação de problemas ou oportunidades, em um cenário de cada vez maiores pressões internas e principalmente externas. O propósito maior é fornecer amplo ambiente de oferta de informações internas e externas, formais e informais, informações sobre as percepções do mercado, informações envolvidas em análises e simulações, enfim, um ambiente integrador das informações disponíveis e relevantes para o sucesso da organização e que crie condições de proatividade para os usuários.

El significat del projecte migratori: les dones parlen de la seva experiència

En aquest article es donen a conèixer els resultats més importants de la segona part d'una recerca sobre migració femenina duta a terme durant els anys 2005-2007 a diferents comunitats autònomes espanyoles, finançada per l"Institut de la Dona (Ministeri de Treball i Afers Socials). En aquesta segona fase, l"equip investigador ha tractat de recollir, a partir d"entrevistes, relats de vida i grups de discussió, la valoració personal de les dones migrants àrabs i llatines sobre el seu projecte migratori. Així mateix, aquest estudi els ha permès evidenciar les dificultats que troben aquestes dones en el procés d'acollida en els àmbits laboral, social, educatiu i, fins i tot, familiar, i quins recursos mobilitzen per superar amb èxit aquestes dificultats. Entre alguns d"aquests recursos destaquen les pràctiques cooperatives i les xarxes de solidaritat que estableixen entre elles en els espais de relació formal i informal on participen. I com aquests espais, en la mesura que són sensibles a les necessitats i als interessos de les dones migrants, esdevenen una veritable porta d'entrada a la societat d'acollida.

Novel pathogenic pathways in diabetic neuropathy.

Diabetic peripheral neuropathy (DPN) is a common complication affecting more than one third of diabetes mellitus (DM) patients. Although all cellular components participating in peripheral nerve function are exposed to and affected by the metabolic consequences of DM, nodal regions, areas of intense interactions between Schwann cells and axons, may be particularly sensitive to DM-induced alterations. Nodes are enriched in insulin receptors, glucose transporters, Na(+) and K(+) channels, and mitochondria, all implicated in the development and progression of DPN. Latest results particularly reinforce the idea that changes in ion-channel function and energy metabolism, both of which depend on axon-glia crosstalk, are among the important contributors to DPN. These insights provide a basis for new therapeutic approaches aimed at delaying or reversing DPN.

Outpatient prescription writing quality in a paediatric general hospital

Introduction The writing of prescriptions is an important aspect of medical practice. Since 2006, the Swiss authorities have decided to impose incentives to prescribe generic drugs. The objectives of this study were 1) to determine the evolution of the outpatient prescription practice in our paediatric university hospital during 2 periods separated by 5 years; 2) to assess the writing quality of outpatient prescriptions during the same period.Materials & Methods Design: Copies of prescriptions written by physicians were collected twice from community pharmacies in the region of our hospital for a 2-month period in 2005 and 2010. They were analysed according to standard criteria regarding both formal and pharmaceutical aspects. Drug prescriptions were classified as a) complete when all criteria for safety were fulfilled, b) ambiguous when there was a danger of a dispensing error because of one or more missing criteria, or c) containing an error.Setting: Paediatric university hospital.Main outcome measures: Proportion of generic drugs; outpatient prescription writing quality.Results: A total of 651 handwritten prescriptions were reviewed in 2005 and 693 in 2010. They contained 1570 drug prescriptions in 2005 (2.4 ± 1.2 drugs per patient) and 1462 in 2010 (2.1 ± 1.1). The most common drugs were paracetamol, ibuprofen, and sodium chloride. A higher proportion of drugs were prescribed as generic names or generics in 2010. Formal data regarding the physicians and the patients were almost complete, except for the patients' weight. Of the drug prescriptions, 48.5% were incomplete, 11.3% were ambiguous, and 3.0% contained an error in 2005. These proportions rose to 64.2%, 15.5% and 7.4% in 2010, respectively.Discussions, Conclusion This study showed that physicians' prescriptions comprised numerous omissions and errors with minimal potential for harm. Computerized prescription coupled with advanced decision support is eagerly awaited.Disclosure of Interest None Declared

Os colégios virtuais e a nova configuração da comunicação científica

Discute as mudanças nos modelos de comunicação formal e informal provocadas pelas tecnologias de informação e comunicação e, em particular, o conceito em formação de colégios virtuais, apresentados muitas vezes como sucedâneos dos colégios invisíveis. Revê o papel reservado à internet no novo cenário, tanto como canal de comunicação quanto como repositório de informações, e apresenta elementos para uma discussão sobre o novo modelo de comunicação científica via rede tendo em vista as discussões sobre acesso gratuito aos periódicos eletrônicos. Conclui atestando o ressurgimento da comunicação científica, suas novas ferramentas e possibilidades interativas ou de interação, como campo complexo de investigação, o qual exige novos estudos com o fim de verificar onde e como se dão as novas confluências.

Residual antimalarial concentrations before treatment in patients with malaria from Cambodia: indication of drug pressure.

BACKGROUND: The Thai-Cambodian border has been known as the origin of antimalarial drug resistance for the past 30 years. There is a highly diverse market for antimalarials in this area, and improved knowledge of drug pressure would be useful to target interventions aimed at reducing inappropriate drug use. METHODS: Baseline samples from 125 patients with falciparum malaria recruited for 2 in vivo studies (in Preah Vihear and Pursat provinces) were analyzed for the presence of 14 antimalarials in a single run, by means of a liquid chromatography-tandem mass spectrometry assay. RESULTS: Half of the patients had residual drug concentrations above the lower limit of calibration for at least 1 antimalarial at admission. Among the drugs detected were the currently used first-line drugs mefloquine (25% and 35% of patients) and piperaquine (15% of patients); the first-line drug against vivax malaria, chloroquine (25% and 41% of patients); and the former first-line drug, quinine (5% and 34% patients). CONCLUSIONS: The findings demonstrate that there is high drug pressure and that many people still seek treatment in the private and informal sector, where appropriate treatment is not guaranteed. Promotion of comprehensive behavioral change, communication, community-based mobilization, and advocacy are vital to contain the emergence and spread of parasite resistance against new antimalarials.

La Generation Sandwich en Suisse Romande: mieux comprendre les facteurs associés avec la santé perçue afin de mieux agir en promotion de la santé [Sandwich Generation in Roman Switzerland : a better understanding of factors linked with perceived health for better acting in health promotion].

The so-called < Sandwich Generation > (SG) is characterized by concurrent and competing professional, familial, and informal caregiving workloads. These stressors pose potential health risks. However, the current knowledge about SG characteristics and perceived state of health are insufficient to allow occupational health nurses to develop evidence-based interventions designed for health promotion. We aimed to describe this population and examine the relationships between these coexisting workloads and their perceived health. This study is based on a descriptive, correlational design. Employees of a Swiss public administration completed an electronic questionnaire. Of 844 respondents, 23 % are SG members. Ages of frailed parents or parents-in-law, co-residence with the latters, children still living at home predict that employees could be members of the SG. Perceived physical health status of SG members is rated better than mental health status. The heterogeneity of SG is reflected in three clusters. Finally, physical health score is the only that differs from the other health scores adjusting for clusters and sex. This study provides a foundation for developing preventive interventions targeting the SG.

Inhibition of voltage-gated Na(+) currents in sensory neurones by the sea anemone toxin APETx2.

BACKGROUND AND PURPOSE: APETx2, a toxin from the sea anemone Anthropleura elegantissima, inhibits acid-sensing ion channel 3 (ASIC3)-containing homo- and heterotrimeric channels with IC(50) values < 100 nM and 0.1-2 µM respectively. ASIC3 channels mediate acute acid-induced and inflammatory pain response and APETx2 has been used as a selective pharmacological tool in animal studies. Toxins from sea anemones also modulate voltage-gated Na(+) channel (Na(v) ) function. Here we tested the effects of APETx2 on Na(v) function in sensory neurones.¦EXPERIMENTAL APPROACH: Effects of APETx2 on Na(v) function were studied in rat dorsal root ganglion (DRG) neurones by whole-cell patch clamp.¦KEY RESULTS: APETx2 inhibited the tetrodotoxin (TTX)-resistant Na(v) 1.8 currents of DRG neurones (IC(50) , 2.6 µM). TTX-sensitive currents were less inhibited. The inhibition of Na(v) 1.8 currents was due to a rightward shift in the voltage dependence of activation and a reduction of the maximal macroscopic conductance. The inhibition of Na(v) 1.8 currents by APETx2 was confirmed with cloned channels expressed in Xenopus oocytes. In current-clamp experiments in DRG neurones, the number of action potentials induced by injection of a current ramp was reduced by APETx2.¦CONCLUSIONS AND IMPLICATIONS: APETx2 inhibited Na(v) 1.8 channels, in addition to ASIC3 channels, at concentrations used in in vivo studies. The limited specificity of this toxin should be taken into account when using APETx2 as a pharmacological tool. Its dual action will be an advantage for the use of APETx2 or its derivatives as analgesic drugs.

PixFRET, an ImageJ plug-in for FRET calculation that can accommodate variations in spectral bleed-throughs.

Fluorescence resonance energy transfer (FRET) allows the user to investigate interactions between fluorescent partners. One crucial issue when calculating sensitized emission FRET is the correction for spectral bleed-throughs (SBTs), which requires to calculate the ratios between the intensities in the FRET and in the donor or acceptor settings, when only the donor or acceptor are present. Theoretically, SBT ratios should be constant. However, experimentally, these ratios can vary as a function of fluorophore intensity, and assuming constant values may hinder precise FRET calculation. One possible cause for such a variation is the use of a microscope set-up with different photomultipliers for the donor and FRET channels, a set-up allowing higher speed acquisitions on very dynamic fluorescent molecules in living cells. Herein, we show that the bias introduced by the differential response of the two PMTs can be circumvented by a simple modeling of the SBT ratios as a function of fluorophore intensity. Another important issue when performing FRET is the localization of FRET within the cell or a population of cells. We hence developed a freely available ImageJ plug-in, called PixFRET, that allows a simple and rapid determination of SBT parameters and the display of normalized FRET images. The usefulness of this modeling and of the plug-in are exemplified by the study of FRET in a system where two interacting nuclear receptors labeled with ECFP and EYFP are coexpressed in living cells.

Sensing the environment : a role for the mouse olfactory subsystems

Summary : Four distinct olfactory subsystems compose the mouse olfactory system, the main olfactory epithelium (MOE), the septal organ of Masera (SO), the vomeronasal organ (VNO) and the Grueneberg ganglion (GG). They are implicated in the sensory modalities of the animal and they evolved to analyse and discriminate molecules carrying chemical messages, such as odorants and pheromones. In this thesis, the VNO, principally implicated in pheromonal communications as well as the GG, which had no function attributed until this work, were investigated from their morphology to their physiological functions, using an array of biochemical and physiological methods. First, the roles of a particular protein, the CNGA4 ion channel, were investigated in the VNO. In the MOE, CNGA4 is expressed as a modulatory channel subunit implicated in odour discrimination and adaptation. Interestingly, this calcium channel is the unique member of the cyclic nucleotide-gated (CNG) family to be expressed in the VNO and up to this work its functions remained unknown. Using a combination of transgenic and knockout mice, as well as histological and physiological approaches, we have characterized CNGA4 expression in the VNO. A strong expression in immature neurons was found as well as in the microvilli of mature neurons (putative site of chemodetection). Interestingly and confirming its dual localisation, the genetic invalidation of the CNGA4 channel has, as consequences, a strong impairment in vomeronasal maturation as well as deficit in pheromone sensing. Thus the CNGA4 channel appears to be a multifunctional protein in the mouse VNO playing essential role(s) in this organ. During the second part of the work, the morphology of the most recently described olfactory subsystem, the Grueneberg ganglion, was investigated in detail. Interestingly we found that glial cells and ciliated neurons compose this olfactory ganglion. This particular morphological aspect was similar to the olfactory AWC neurons from C. elegans which was used for further comparisons. Thus as for AWC neurons, we found that GG neurons are sensitive to temperature changes and are able to detect highly volatile molecules. Indeed, the presence of alarm pheromones (APs) secreted by stressed mice, elicit strong cellular responses, as well as a GG dependent behavioural changes. Investigations on the signaling elements present in GG neurons revealed that, as for AWC neurons, or pGC-D expressing neurons from the MOE, proteins participating in a cGMP pathway were found in GG neurons such as pGC-G and CNGA3 channels. These two proteins might be implicated in chemosensing as well as in thermosensing, two apparent properties of this organ. In this thesis, the multisensory modalities of two mouse olfactory subsystems were described and are related to a high degree of complexity required for the animal to sense its environment

Flow resistance equations for mountain rivers

Three models of flow resistance (a Keulegan-type logarithmic law and two models developed for large-scale roughness conditions: the full logarithmic law and a model based on an inflectional velocity profile) were calibrated, validated and compared using an extensive database (N = 1,533) from rivers and flumes, representative of a wide hydraulic and geomorphologic range in the field of gravel-bed and mountain channels. It is preferable to apply the model based on an inflectional velocity profile in the relative submergence (y/d90) interval between 0.5 and 15, while the full logarithmic law is preferable for values below 0.5. For high relative submergence, above 15, either the logarithmic law or the full logarithmic law can be applied. The models fitted to the coarser percentiles are preferable to those fitted to the median diameter, owing to the higher explanatory power achieved by setting a model, the smaller difference in the goodness-of-fit between the different models and the lower influence of the origin of the data (river or flume).