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C.C.C.T. and J.R.S. at Southwest Research Institute were funded by NASA Outer Planets Research grant NNX14AC63G and Planetary Astronomy grant NNX11AD61G. M.A.L.V. was funded by the Spanish Ministerio de Economia y Competitividad and by FEDER funds under project ESP2015-65064-C2-1-P (MINECO/FEDER)

Resumen Para describir los hallazgos ecograficos de la orquiepididimitis aguda complicada disenamos un estudio descriptivo retrospectivo de casos entre 2006-2013. Registramos 75 casos de orquiepididimitis aguda severa, presentando complicaciones 15 pacientes (20%). La media de edad fue 54 anos (rango 15-84). Las principales manifestaciones clinicas fueron dolor escrotal y edema testicular, encontrando: orquiepididimitis cronica, absceso escrotal, absceso intratesticular, piocele, isquemia testicular y atrofia testicular en el contexto de una orquitis cronica. Fue preciso realizar cirugia en 9 casos. La ecografia identifica lesiones especificas cuyo manejo precoz permite el tratamiento conservador y un seguimiento del proceso sin recurrir a exploraciones quirurgicas innecesarias. Se revisan los datos clinicos y su correlacion con los patrones ecograficos encontrados en nuestro estudio. La orquiepididimitis es un problema habitual que puede derivar en complicaciones de variada gravedad. El conocimiento de los signos ecograficos nos permitira establecer un diagnostico precoz y fiable, eligiendo el tratamiento adecuado.

SUMMARY Cells adopt distinct signaling pathways to optimize cell locomotion in different physical microenvironments. However, the underlying mechanism that enables cells to sense and respond to physical confinement is unknown. Using microfabricated devices and substrate-printing methods along with FRET-based biosensors, we report that, as cells transition from unconfined to confined spaces, intracellular Ca2+ level is increased, leading to phosphodiesterase 1 (PDE1)-dependent suppression of PKA activity. This Ca2+ elevation requires Piezo1, a stretch-activated cation channel. Moreover, differential regulation of PKA and cell stiffness in unconfined versus confined cells is abrogated by dual, but not individual, inhibition of Piezo1 and myosin II, indicating that these proteins can independently mediate confinement sensing. Signals activated by Piezo1 and myosin II in response to confinement both feed into a signaling circuit that optimizes cell motility. This study provides a mechanism by which confinement-induced signaling enables cells to sense and adapt to different physical microenvironments., In Brief Hung et al. demonstrate that a Piezo1-dependent intracellular calcium increase negatively regulates protein kinase A (PKA) as cells transit from unconfined to confined spaces. The Piezo1/PKA and myosin II signaling modules constitute two confinement-sensing mechanisms. This study provides a paradigm by which signaling enables cells to sense and adapt to different microenvironments.

As an organism is exposed to pathogens during very early development, specific defense mechanisms must take effect. In this study, we used a germ-free zebrafish embryo model to show that osmotic stress regulates the activation of immunity and host protection in newly hatched embryos. Mechanistically, skin keratinocytes were responsible for both sensing the hyposmolarity of the aquatic environment and mediating immune effector mechanisms. This occurred through a transient potential receptor vanilloid 4/Ca2+/TGF-β–activated kinase 1/NF-κB signaling pathway. Surprisingly, the genes encoding antimicrobial effectors, which do not have the potential to cause tissue damage, are constitutively expressed during development, independently of both commensal microbes and osmotic stress. Our results reveal that osmotic stress is associated with the induction of developmental immunity in the absence of tissue damage and point out to the embryo skin as the first organ with full capacities to mount an innate immune response.

F.G.G. was partly funded by a CSIC JAE-Doc grant financed by the European Social Fund. F.G.G., M.-A.L.V., and M.G.C. thank the Spanish MICINN for funding support through the CONSOLIDER program ASTROMOLCSD2009-00038 and through projects AYA2011-23552/ESP and AYA2012-39691-C02-01. This work has also been partially funded by the ESA-CNES project Mars Climate Database and Physical Models.

Regulated mucin secretion from specialized goblet cells by exogenous agonist-dependent (stimulated) and -independent (baseline) manner is essential for the function of the epithelial lining. Over extended periods, baseline release of mucin can exceed quantities released by stimulated secretion, yet its regulation remains poorly characterized. We have discovered that ryanodine receptor-dependent intracellular Ca2+ oscillations effect the dissociation of the Ca2+-binding protein, KChIP3, encoded by KCNIP3 gene, from mature mucin-filled secretory granules, allowing for their exocytosis. Increased Ca2+ oscillations, or depleting KChIP3, lead to mucin hypersecretion in a human differentiated colonic cell line, an effect reproduced in the colon of Kcnip3-/- mice. Conversely, overexpressing KChIP3 or abrogating its Ca2+-sensing ability, increases KChIP3 association with granules, and inhibits baseline secretion. KChIP3 therefore emerges as the high-affinity Ca2+ sensor that negatively regulates baseline mucin secretion. We suggest KChIP3 marks mature, primed mucin granules, and functions as a Ca2+ oscillation-dependent brake to control baseline secretion. This work was funded by grants from the Spanish Ministry of Economy and Competitiveness (BFU2013-44188-P to VM, SAF2015-69762R to MAV and SAF2017-89554-R to JRN) and FEDER Funds. We acknowledge support of the Spanish Ministry of Economy and Competitiveness, through the Programmes “Centro de Excelencia Severo Ochoa 2013- 2017” (SEV-2012-0208 & SEV-2013-0347) and Maria de Maeztu Units of Excellence in R&D (MDM-2015- 0502). This work reflects only the authors’ views, and the EU Community is not liable for any use that may be made of the information contained therein.

The molecular mechanism by which progesterone (P4) modulates the transport of ova and embryos along the oviduct is not fully resolved. We report a rapid response to P4 and agonists of γ-aminobutyric acid receptors A and B (GABA

The molecular mechanism by which progesterone (P4) modulates the transport of ova and embryos along the oviduct is not fully resolved. We report a rapid response to P4 and agonists of γ-aminobutyric acid receptors A and B (GABA A/B ) in the mouse oviduct that was characterized by oscillatory Ca 2+ signals and increased ciliary beat frequency (CBF). Pharmacological manipulation, genetic ablation, and siRNA-mediated knockdown in oviductal cells, as well as overexpression experiments in HEK 293T cells, confirmed the participation of the cationic channel TRPV4, different subunits of GABA A (α1 to α3, β2, and β3), and GABA B1 in P4-induced responses. TRPV4-mediated Ca 2+ entry in close proximity to the inositol trisphosphate receptor was required to initiate and maintain Ca 2+ oscillations after P4 binding to GABA A and transactivation of G i/o protein–coupled GABA B receptors. Coimmunoprecipitation experiments and imaging of native tissue and HEK 293T cells demonstrated the close association of GABA A and GABA B1 receptors and the activation of G i/o proteins in response to P4 and GABA receptor agonists, confirming a molecular mechanism in which P4 and GABAergic agonists cooperatively stimulate cilial beating.

Ion channels are well placed to transduce environmental cues into signals used by cells to generate a wide range of responses, but little is known about their role in the regulation of RNA metabolism. Here we show that the TRPV4 cation channel binds the DEAD-box RNA helicase DDX3X and regulates its function. TRPV4-mediated Ca2+ influx releases DDX3X from the channel and drives DDX3X nuclear translocation, a process that involves calmodulin (CaM) and the CaM-dependent kinase II. Genetic depletion or pharmacological inhibition of TRPV4 diminishes DDX3X-dependent functions, including nuclear viral export and translation. Furthermore, TRPV4 mediates Ca2+ influx and nuclear accumulation of DDX3X in cells exposed to the Zika virus or the purified viral envelope protein. Consequently, targeting of TRPV4 reduces infectivity of dengue, hepatitis C and Zika viruses. Together, our results highlight the role of TRPV4 in the regulation of DDX3X-dependent control of RNA metabolism and viral infectivity., The ion channel TRPV4 senses many environmental cues, but its role in virus infection is not known. Here, Doñate-Macián et al. show that Zika virus induces TRPV4-mediated Ca2+ influx into cells, resulting in the nuclear accumulation of the DDX3X RNA helicase, which increases virus replication.

We simulate the hydrogen density near the exobase of Mars, using the 3-D Martian Global Circulation Model of Laboratoire de Météorologie Dynamique, coupled to an exospheric ballistic model to compute the downward ballistic flux. The simulated hydrogen distribution near the exobase obtained at two different seasons—Ls = 180° and Ls = 270°—is close to Zero Net Ballistic Flux equilibrium. In other words, the hydrogen density near the exobase adjusts to have a balance between the local upward ballistic and the downward ballistic flux due to a short lateral migration time in the exosphere compared to the vertical diffusion time. This equilibrium leads to a hydrogen density n near the exobase directly controlled by the exospheric temperature T by the relation nT5/2 = constant. This relation could be used to extend 1-D hydrogen exospheric model of Mars used to derive the hydrogen density and escape flux at Mars from Lyman-α observations to 3-D model based on observed or modeled exospheric temperature near the exobase, without increasing the number of free parameters. ©2018. American Geophysical Union. All Rights Reserved., This project was partly funded by the Programme National de Planetologie and Programme National Soleil Terre and by the Centre National d'Etudes Spatiales. This work has been partially funded by the European Union Horizon 2020 Programme (H2020 Compet-082014) under grant agreement UPWARDS-633127.

López-Valverde, M. A. et al., The Martian mesosphere and thermosphere, the region above about 60 km, is not the primary target of the ExoMars 2016 mission but its Trace Gas Orbiter (TGO) can explore it and address many interesting issues, either in-situ during the aerobraking period or remotely during the regular mission. In the aerobraking phase TGO peeks into thermospheric densities and temperatures, in a broad range of latitudes and during a long continuous period. TGO carries two instruments designed for the detection of trace species, NOMAD and ACS, which will use the solar occultation technique. Their regular sounding at the terminator up to very high altitudes in many different molecular bands will represent the first time that an extensive and precise dataset of densities and hopefully temperatures are obtained at those altitudes and local times on Mars. But there are additional capabilities in TGO for studying the upper atmosphere of Mars, and we review them briefly. Our simulations suggest that airglow emissions from the UV to the IR might be observed outside the terminator. If eventually confirmed from orbit, they would supply new information about atmospheric dynamics and variability. However, their optimal exploitation requires a special spacecraft pointing, currently not considered in the regular operations but feasible in our opinion. We discuss the synergy between the TGO instruments, specially the wide spectral range achieved by combining them. We also encourage coordinated operations with other Mars-observing missions capable of supplying simultaneous measurements of its upper atmosphere. © 2018, Springer Science+Business Media B.V., part of Springer Nature., The IAA/CSIC team has been supported by the European Union’s Horizon 2020 Programme (H2020-Compet-08-2014) under grant agreement UPWARDS-633127, by CSIC Proyecto Intramural 201450E022 and by the Plan Nacional del Espacio ESP2015-65064-C2-1-P (MINECO/FEDER). This research was partly supported by the SCOOP/BRAIN program of the Belgian Science Policy Office (BELSPO). We acknowledge the work of Sabrina Guilbon during her Master internship at LATMOS on the development of the technique to compare the slant profiles of SPICAM and the LMD GCM. M.R.P. thanks UKSA for support under grant ST/I003061/1 and ST/P001262/1. C.F.W. acknowledges funding support from the UK Space Agency. Work by A.K., D.J.MC. and D.M.K. at the Jet Propulsion Laboratory, California Institute of Technology was performed under a contract with the National Aeronautics and Space Administration. OK, NI and AF thanks funding from Roscosmos for the ACS operation support and science funding from The Federal Agency of scientific organization (Planeta No. 0028-2014-0004).

Regulated mucin secretion is essential for the formation of the mucus layer that protects the underlying epithelial cells from foreign particles. Alterations in the quantity or quality of secreted mucins are therefore detrimental to airway and colon physiology. Based on various biochemical assays in several human cell lines, we report here that Na(+)/Ca(2+) exchanger 2 (NCX2) works in conjunction with transient receptor potential cation channel subfamily M member 4 (TRPM4), and perhaps TRPM5, Na(+) channels to control Ca(2+)-mediated secretion of both mucin 2 (MUC2) and MUC5AC from HT29-18N2 colonic cancer cells. Differentiated normal bronchial epithelial (NHBE) cells and tracheal cells from patients with cystic fibrosis (CFT1-LC3) expressed only TRPM4 and all three isoforms of NCXs. Blocking the activity of TRPM4 or NCX proteins abrogated MUC5AC secretion from NHBE and CFT1-LC3 cells. Altogether, our findings reveal that NCX and TRPM4/TRPM5 are both required for mucin secretion. We therefore propose that these two proteins could be potential pharmacological targets to control mucus-related pathologies such as cystic fibrosis.

Summary Functional transient receptor potential (TRP) channels result from the assembly of four subunits. Here, we show an interaction between the pre-S1, TRP, and the ankyrin repeat domain (ARD)-S1 linker domains of TRPV1 and TRPV4 that is essential for proper channel assembly. Neutralization of TRPV4 pre-S1 K462 resulted in protein retention in the ER, defective glycosylation and trafficking, and unresponsiveness to TRPV4-activating stimuli. Similar results were obtained with the equivalent mutation in TRPV1 pre-S1. Molecular dynamics simulations revealed that TRPV4-K462 generated an alternating hydrogen network with E745 (TRP box) and D425 (pre-S1 linker), and that K462Q mutation affected subunit folding. Consistently, single TRPV4-E745A or TRPV4-D425A mutations moderately affected TRPV4 biogenesis while double TRPV4-D425A/E745A mutation resumed the TRPV4-K462Q phenotype. Thus, the interaction between pre-S1, TRP, and linker domains is mandatory to generate a structural conformation that allows the contacts between adjacent subunits to promote correct assembly and trafficking to the plasma membrane.

The mobilization pattern and functionality of endothelial progenitor cells after an acute ischemic event remain largely unknown. The aim of our study was to characterize and compare the short- and long-term mobilization of endothelial progenitor cells and circulating endothelial cells after acute myocardial infarction or atherothrombotic stroke, and to determine the relationship between these cell counts and plasma concentrations of vascular cell adhesion molecule (VCAM-1) and Von Willebrand factor (VWF) as surrogate markers of endothelial damage and inflammation. In addition, we assessed whether endothelial progenitor cells behave like functional endothelial cells. We included 150 patients with acute myocardial infarction or atherothrombotic stroke and 145 controls. Endothelial progenitor cells [CD45-, CD34+, KDR+, CD133+], circulating endothelial cells [CD45-, CD146+, CD31+], VWF, and VCAM-1 levels were measured in controls (baseline only) and in patients within 24h (baseline) and at 7, 30, and 180 days after the event. Myocardial infarction patients had higher counts of endothelial progenitor cells and circulating endothelial cells than the controls (201.0/mL vs. 57.0/mL; p

The superrotation of the atmospheres of slowly rotating bodies is a long-standing problem yet unsolved in atmospheric dynamics. On Venus, the most extreme case known of superrotation, this is accompanied and influenced by a recurrent planetary-scale cloud structure, known as the Y feature. So far, no model has simultaneously reproduced its shape, temporal evolution, related wind field, nor the relation between its dynamics and the unknown UV-absorbing aerosol that produces its dark morphology. In this paper we present an analytical model for a Kelvin-like wave that offers an explanation of these peculiarities. Under Venus cyclostrophic conditions, this wave is equatorially and vertically trapped where zonal winds peak and extends 7 km in altitude, and its vertical wind perturbations are shown to produce upwelling of the UV absorber. The Y-feature morphology and its 30 day evolution are reproduced as distortions of the wave structure by the Venus winds.

Calcium signaling participates in different cellular processes leading to cell migration. TRPV4, a non-selective cation channel that responds to mechano-osmotic stimulation and heat, is also involved in cell migration. However, the mechanistic involvement of TRPV4 in cell migration is currently unknown. We now report that expression of the mutant channel TRPV4-(121)AAWAA (lacking the phosphoinositide-binding site (121)KRWRK(125) and the response to physiological stimuli) altered HEK293 cell migration. Altered migration patterns included periods of fast and persistent motion followed by periods of stalling and turning, and the extension of multiple long cellular protrusions. TRPV4-WT overexpressing cells showed almost complete loss of directionality with frequent turns, no progression, and absence of long protrusions. Traction microscopy revealed higher tractions forces in the tail of TRPV4-(121)AAWAA than in TRPV4-WT expressing cells. These results are consistent with a defective and augmented tail retraction in TRPV4-(121)AAWAA- and TRPV4-WT-expressing cells, respectively. The activity of calpain, a protease implicated in focal adhesion (FA) disassembly, was decreased in TRPV4-(121)AAWAA compared with TRPV4-WT-expressing cells. Consistently, larger focal adhesions were seen in TRPV4-(121)AAWAA compared with TRPV4-WT-expressing HEK293 cells, a result that was also reproduced in T47D and U87 cells. Similarly, overexpression of the pore-dead mutant TRPV4-M680D resumed the TRPV4-(121)AAWAA phenotype presenting larger FA. The migratory phenotype obtained in HEK293 cells overexpressing TRPV4-(121)AAWAA was mimicked by knocking-down TRPC1, a cationic channel that participates in cell migration. Together, our results point to the participation of TRPV4 in the dynamics of trailing adhesions, a function that may require the interplay of TRPV4 with other cation channels or proteins present at the FA sites.

Vesicouterine fistula without vaginal leakage of urine, cyclic hematuria and amenorrhea is a rare condition, identified as Youssef’s syndrome. The most common cause of this syndrome is trauma during a cesarean section. Different therapeutical approaches that include conservative treatment, fulguration, hormonal therapy and open, laparoscopic or robotic surgeries have been mentioned in the literature. Herein a case in a 37-year-old patient is reported. Conservative treatment with urinary drainage was successful because the fistula was recognized in the immediate postoperative period.

Lipopolysaccharides (LPS), the major components of the wall of gram-negative bacteria, trigger powerful defensive responses in the airways via mechanisms thought to rely solely on the Toll-like receptor 4 (TLR4) immune pathway. Here we show that airway epithelial cells display an increase in intracellular Ca2+ concentration within seconds of LPS application. This response occurs in a TLR4-independent manner, via activation of the transient receptor potential vanilloid 4 cation channel (TRPV4). We found that TRPV4 mediates immediate LPS-induced increases in ciliary beat frequency and the production of bactericidal nitric oxide. Upon LPS challenge TRPV4-deficient mice display exacerbated ventilatory changes and recruitment of polymorphonuclear leukocytes into the airways. We conclude that LPS-induced activation of TRPV4 triggers signaling mechanisms that operate faster and independently from the canonical TLR4 immune pathway, leading to immediate protective responses such as direct antimicrobial action, increase in airway clearance, and the regulation of the inflammatory innate immune reaction., LPS is a major component of gram-negative bacterial cell walls, and triggers immune responses in airway epithelium by activating TLR4. Here the authors show that LPS also activates TRPV4, thereby inducing fast defense responses such as nitric oxide production and increased ciliary beating in mice.

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Evaluating eHealth solutions to improve the management of Diabetes requires a multidimensional perspective but, at the same time, there is need to converge the different dimensions in order to make decisions towards further stages of innovation. The work described in this paper informs on how the results of a European funded project have been re-elaborated in order to collect data for a cost-effectiveness analysis carried out through the MAFEIP tool that, since 2015, the European Commission has made available to assess innovations in health and social care for European regions.

Iatrogenic esophageal perforations are rare but associated with a high morbidity and mortality. Secondary to placing a Sengstaken ballon are even more extraordinary because of the infrequency which this measure is used to control upper gastrointestinal bleeding. Therefore, we think it is of interest to communicate this complication, to remember the need to check the correct placement of the Sengstaken ballon before insufflation, since it would help further decrease this complication.

International audience; We present here the thermal structure of the upper atmosphere of Venus predicted by a full self-consistent Venus General Circulation Model (VGCM) developed at Laboratoire de MMétéorologie Dynamique (LMD) and extended up to the thermosphere of the planet. Physical and photochemical processes relevant at those altitudes, plus a non-orographic GW parameterisation, have been added. All those improvements make the LMD-VGCM the only existing ground-to-thermosphere 3D model for Venus: a unique tool to investigate the atmosphere of Venus and to support the exploration of the planet by remote sounding. The aim of this paper is to present the model reference results, to describe the role of radiative, photochemical and dynamical effects in the observed thermal structure in the upper mesosphere/lower thermosphere of the planet. The predicted thermal structure shows a succession of warm and cold layers, as recently observed. A cooling trend with increasing latitudes is found during daytime at all altitudes, while at nighttime the trend is inverse above about 110 km, with an atmosphere up to 15 K warmer towards the pole. The latitudinal variation is even smaller at the terminator, in agreement with observations. Below about 110 km, a nighttime warm layer whose intensity decreases with increasing latitudes is predicted by our GCM. A comparison of model results with a selection of recent measurements shows an overall good agreement in terms of trends and order of magnitude. Significant data-model discrepancies may be also discerned. Among them, thermospheric temperatures are about 40-50 K colder and up to 30 K warmer than measured at terminator and at nighttime, respectively. The altitude layer of the predicted mesospheric local maximum (between 100 and 120 km) is also higher than observed. Possible interpretations are discussed and several sensitivity tests performed to understand the data-model discrepancies and to propose future model improvements.

International audience; Model studies of the ionosphere of Mars under daytime conditions reveal that for solar zenith angles (SZAs) of 0°-40°, the shapes and magnitudes of the electron density profiles Ne(h) change by only small amounts. This suggests that mid-day observations made by MAVEN instruments along slanted orbit segments can be used to represent vertical profiles. The total electron content (TEC), defined as the height integral of Ne(h), is a measure of the cold plasma reservoir of the martian ionosphere. During MAVEN's Deep-Dip-#2 campaign of April 2015, observations of total ion density by NGIMS and electron density by LPW from periapse (~130 km) to 400 km were used to form topside—validated by independent diagnostics and models. Orbit-by-orbit changes in topside TEC were then used to assess the magnitudes of plasma escape associated with both large and small changes in the topside slope of Ne(h)—called an “ionopause episode.” The TEC changes due to these episodes, generalized to a global change, resulted in an escape flux of ~3 - 6 x 1024 ions/sec, an escape rate consistent with prior observation by Phobos-2, Mars Express, and MAVEN's own in-situ studies.

TRPV4 cation channel activation by cytochrome P450-mediated derivatives of arachidonic acid (AA), epoxyeicosatrienoic acids (EETs), constitute a major mechanisms of endothelium-derived vasodilatation. Besides, TRPV4 mechano/osmosensitivity depends on phospholipase A2 (PLA2) activation and subsequent production of AA and EETs. However, the lack of evidence for a direct interaction of EETs with TRPV4 together with claims of EET-independent mechanical activation of TRPV4 has cast doubts on the validity of this mechanism. We now report: 1) The identification of an EET-binding pocket that specifically mediates TRPV4 activation by 5′,6′-EET, AA and hypotonic cell swelling, thereby suggesting that all these stimuli shared a common structural target within the TRPV4 channel; and 2) A structural insight into the gating of TRPV4 by a natural agonist (5′,6′-EET) in which K535 plays a crucial role, as mutant TRPV4-K535A losses binding of and gating by EET, without affecting GSK1016790A, 4α-phorbol 12,13-didecanoate and heat mediated channel activation. Together, our data demonstrates that the mechano- and osmotransducing messenger EET gates TRPV4 by a direct action on a site formed by residues from the S2-S3 linker, S4 and S4-S5 linker. The research is supported by awards from the Spanish Ministry of Economy and Competitiveness (Grants SAF2015-69762-R to M.A.V. and J.M.F.-F., and MDM-2014-0370 through the “María de Maeztu” Programme for Units of Excellence in R&D to “Departament de Ciències Experimentals i de la Salut”), and FEDER Funds (Fondo Europeo de Desarrollo Regional). M.I.-S. holds a “Juan de la Cierva-Formación” Fellowship funded by the Spanish Ministry of Economy and Competitiveness. FGN acknowledge the support of FONDECYT Grant 1170733 and The Centro Interdisciplinario de Neurociencia de Valparaíso (CINV) is a Millennium Institute supported by the Millennium Scientific Initiative of the Ministerio de Economía, Fomento y Turismo. R.V.S. is funded by CONICYT PCHA/Doctorado Nacional 2013-21130631 fellowship

Benign paroxysmal torticollis of infancy (BPTI) is a rare paroxysmal disorder characterized by recurrent episodes of head tilt and accompanying general symptoms which remit spontaneously. The rare association with gain-of-function CACNA1A mutations, similar to hemiplegic migraine, has been reported. We report here two new BPTI patients from the same family carrying a heterozygous mutation in the CACNA1A gene leading to the change p.Glu533Lys. Functional analysis revealed that this mutation induces a loss of channel function due to impaired gating by voltage and much lower current density. Our data suggest that BPTI, a periodic syndrome commonly considered a migraine precursor, constitutes an age-specific manifestation of defective neuronal calcium channel activity.

Resumen Objetivo Revisar los hallazgos ecograficos mas relevantes asociados al cancer de vesicula biliar. Material y metodo Estudio descriptivo y retrospectivo de las caracteristicas clinicas y estudios de imagen en pacientes con neoplasia de vesicula biliar en el periodo 2000-2011 en el Hospital General Reina Sofia de Murcia. Resultados Fueron hallados 15 casos de cancer vesicular, de los que 9 eran mujeres. La edad media fue 77 anos (rango 61-96). El dolor fue el principal motivo de consulta. Presentaban colelitiasis 13 casos, tabaquismo 2 casos y obesidad 3 casos. La ecografia comprobo engrosamiento de la pared vesicular (> 4 mm) en 8 casos, masa intraluminal en 4, vesicula escleroatrofica en 2 y masa que reemplaza la vesicula en uno. Solo en 4 casos hubo la sospecha preoperatoria de carcinoma vesicular. Siguiendo la estadificacion pTNM, 4 pacientes presentaban un carcinoma in situ (Tis), un caso T1a, 6 casos T2, 3 casos T3 y un caso T4. En 7 casos, la unica prueba radiologica preoperatoria fue la ecografia y en otros 8 se completo el estudio con una TC abdominal. Conclusion El diagnostico precoz del cancer vesicular es raro. La orientacion diagnostica por ecografia es limitada; solo el engrosamiento parietal localizado coexistente con litiasis vesicular parece significativo en estadios tempranos. La imagen de masa y calculo ocupando la vesicula se asocia a etapas avanzadas de la enfermedad.

La piometra es una acumulación de pus en la cavidad endometrial. Aparece cuando existe una estenosis del orificio cervical debida a procesos malignos de cuerpo uterino o de cérvix, tras tratamientos con cirugía o radioterapia y por atrofia senil. Se presenta el caso de una paciente de 84 años remitida al Servicio de Urgencias Hospitalarias del Hospital Universitario Basurto, en Bilbao, España por el médico de la residencia donde se encuentra institucionalizada debido a que presentaba fiebre mantenida desde hacía dos semanas, sin focalidad aparente, diagnosticada como infección urinaria y tratada con amoxicilina-clavulánico. Por los exámenes imagenológicos se diagnosticó piometra en útero bicorne. Fue sometida al drenaje del piometra por vía vaginal, bajo anestesia general, tras dilatación mecánica del canal cervical. Se puso tratamiento con ertapenen. La evolución fue satisfactoria. Por lo poco común del caso se decidió su presentación.

La práctica del consentimiento informado (CI) en Salud Mental es inhabitual, más aún para los pacientes psicóticos, a pesar de que tanto la legislación vigente, como las declaraciones de asociaciones profesionales, organizaciones de pacientes y códigos deontológicos defienden el consentimiento informado y la autonomía del paciente, también para las personas con psicosis. Es habitual que pacientes y allegados desconozcan el alcance, límites y riesgos del tratamiento farmacológico usual o la existencia de otros abordajes Las razones del déficit de CI pueden hallarse en las peculiaridades de estos pacientes, pero también en el presupuesto de que la psicosis impacta en el mismo núcleo de la persona, y por ello se ve al afectado como incapaz de comprender y consentir. Coexisten hoy dos estilos diferentes de acoger al paciente con dificultades de tipo psicótico: uno, la corriente principal que tiene como objetivo bloquear el proceso psicótico y revertirlo mediante el uso principal de antipsicóticos, y otro, que incluye diversos modelos que acogen a la persona psicótica con sus dificultades, que propone construir un marco de comprensión para sus experiencias. Los resultados no muestran superioridad del modelo dominante, más bien todo lo contrario. Cuando se da la palabra a los usuarios estos defienden su autonomía y derecho a decidir, rechazando los modelos coercitivos. El CI, dar poder para decidir al paciente, además de un derecho es también un factor de recuperación para muchos pacientes. Su puesta en práctica necesitaría cambios significativos en la formación de los profesionales y en la constitución de las actuales Redes Asistenciales de Salud Mental., Informed consent (IC) in Mental Health care is unusual, especially for psychotic patients. However, current legislation, statements of professional associations, patient organizations and deontological codes advocate informed consent and patients' autonomy, also for people with psychosis. Patients and their relatives usually are unaware of the scope, limits and risks of drug treatment and the existence of other approaches. The reasons for the IC’s lack can be found in the peculiarities of these patients, but also on the assumption that psychosis impacts the core of the person, and therefore they are unfit of understanding and consent. Today there are two different ways to receive the patient with psychosis problems: first, the mainstream whose objective is to block the process and reverse psychotic symptoms principally using antipsychotics drugs, and another one, that includes various clinic models, that receive psychotic person with their difficulties, proposing to build a framework of understanding for their experiences. The outcomes don’t reveal superiority for the mainstream model, rather the opposite. When listening to the users, they clearly opt for their autonomy and right to choose, rejecting coercive models. Informed consent is a right that empowers the patients and also a recovery factor for many of them. Its implementation will require significant changes in the training of professionals and in the current Mental Health Care networks.

A case of bowel intussusception in a 43-year-old woman with a history of Roux-en-Y gastric bypass surgery is presented.

The surname of author Cathy Quantin-Nataf was misspelled ‘Quantin-Nata’ , authors Ehouarn Millour and Roland Young were missing from the ACS Science Team list, and minor changes have been made to the author and affiliation lists; see accompanying Amendment. These errors have been corrected online.

This study tests the effectiveness of an acceptance/defusion intervention in reducing experimentally induced generalized avoidance. After the formation of two 6-member equivalence classes, 23 participants underwent differential conditioning with two elements from each class: A1 and B1 were paired with mild electric shock, whereas A2 and B2 were paired with earning points. Participants learned to produce avoidance and approach responses to these respective stimuli and subsequently showed transfer of functions to non-directly conditioned equivalent stimuli from Class 1 (i.e., D1 and F1 evoked avoidance responses) and Class 2 (i.e., D2 and F2 evoked approach responses). Participants were then randomly assigned to either a motivational protocol (MOT) in which approaching previously avoided stimuli was given a general value, or to a defusion protocol (DEF) in which defusion (a component of Acceptance and Commitment Therapy) was trained while approaching previously avoided stimuli was connected to personally meaningful examples. A post-hoc control group (CMOT) was conducted with 16 participants to control for differences in protocol length between the former two groups. All participants in the DEF group showed a complete suppression of avoidance responding in the presence of Class 1 stimuli (A1-F1 and additional novel stimuli in relation to them), as compared to 40% of participants in the MOT condition and 20% in the CMOT condition. The acceptance/defusion protocol eliminated experimentally induced avoidance responding even for stimuli that elicited autonomic fear responses.

Exposure techniques rely on the assumption that the extinction of the classically conditioned response (i.e., fear) will result in the disruption of limiting forms of avoidance behavior, both directly trained and derived/indirectly established. This report presents translational research that attempts to test this assumption in laboratory conditions in two experiments with human volunteers. The procedure in both experiments included six phases: (1) conditional discrimination training for the formation of two 6-member equivalence classes; (2) classical conditioning of elicited responses to Class 1 (A1/B1) and Class 2 (A2/B2) members in the white context, followed by conditioning of avoidance/approach responses to Class 1/Class 2 members, respectively, in the green context; (3) test for the transfer of avoidance/approach functions and of eliciting respondent functions to D1/F1 and D2/F2 in the green context; (4) extinction of classically conditioned responses to A1/B1 in the white context; (5) test of the effects of respondent extinction on avoidance responding to the A, B, D, and F stimuli in the green context; and (6) test of derived symmetry and equivalence relations. Results show that after successful respondent extinction in the white context, only 33.3% participants stopped showing avoidance behavior in the green context, and that respondent elicitation was reinstalled during the test (Phase 5). In Phase 4 of Experiment 2, in addition to undergoing respondent extinction, participants were instructed that the white and green contexts were similar. Results show that after successful respondent extinction in the white context during Phase 4, only 10% participants stopped showing avoidance behavior in the green context, and that respondent elicitation was almost eliminated during the test (Phase 5). We discuss these findings and their applied implications.

[1] We describe the Mars ionosphere with unprecedented detail in 3-D, as simulated by a Mars general circulation model (the Laboratoire de Meteorologie Dynamique Mars GCM), and compare it with recent measurements. The model includes a number of recent extensions and improvements. Different simulations for a full Martian year have been performed. The electron density at the main ionospheric peak is shown to vary with the Sun-Mars distance and with the solar variability, both in the long-term (11 year solar cycle) and on shorter temporal scales (solar rotation). The main electronic peak is shown to be located at the same pressure level during all the Martian year. As a consequence, its altitude varies with latitude, local time, and season according to the natural expansions and fluctuations of the neutral atmosphere, in agreement with previous models. The model predicts a nighttime ionosphere due only to photochemistry. The simulated ionosphere close to the evening terminator is in agreement with observations. No effort has been made to explain the patchy ionosphere observed in the deep nightside. We have compared the modeled ionosphere with Mars Global Surveyor and Mars Advanced Radar for Subsurface and Ionosphere Sounding data. The model reproduces the solar zenith angle variability of the electron density and the altitude of the peak, although it underestimates the electron density at the main peak by about 20%. The electron density at the secondary peak is strongly underestimated by the model, probably due to a very crude representation of the X-ray solar flux. This is one of the aspects that needs a revision in future versions of the model.

Most transient receptor potential (TRP) channels are regulated by phosphatidylinositol-4,5-biphosphate (PIP 2 ), although the structural rearrangements occurring on PIP 2 binding are currently far from clear. Here we report that activation of the TRP vanilloid 4 (TRPV4) channel by hypotonic and heat stimuli requires PIP 2 binding to and rearrangement of the cytosolic tails. Neutralization of the positive charges within the sequence 121 KRWRK 125 , which resembles a phosphoinositide-binding site, rendered the channel unresponsive to hypotonicity and heat but responsive to 4α-phorbol 12,13-didecanoate, an agonist that binds directly to transmembrane domains. Similar channel response was obtained by depletion of PIP 2 from the plasma membrane with translocatable phosphatases in heterologous expression systems or by activation of phospholipase C in native ciliated epithelial cells. PIP 2 facilitated TRPV4 activation by the osmotransducing cytosolic messenger 5′-6’-epoxyeicosatrienoic acid and allowed channel activation by heat in inside-out patches. Protease protection assays demonstrated a PIP 2 -binding site within the N-tail. The proximity of TRPV4 tails, analyzed by fluorescence resonance energy transfer, increased by depleting PIP 2 mutations in the phosphoinositide site or by coexpression with protein kinase C and casein kinase substrate in neurons 3 (PACSIN3), a regulatory molecule that binds TRPV4 N-tails and abrogates activation by cell swelling and heat. PACSIN3 lacking the Bin-Amphiphysin-Rvs (F-BAR) domain interacted with TRPV4 without affecting channel activation or tail rearrangement. Thus, mutations weakening the TRPV4–PIP 2 interacting site and conditions that deplete PIP 2 or restrict access of TRPV4 to PIP 2 —in the case of PACSIN3—change tail conformation and negatively affect channel activation by hypotonicity and heat.

Resumen Objetivo Presentacion de nuestra experiencia desde octubre del 2009 hasta diciembre del 2011 y comparacion de los resultados y las complicaciones con el amplio estudio publicado en el American Journal of Obstetrics and Gynecology (AJOG) en 2011. Material y metodos Estudio prospectivo de nuestros primeros 55 carcinomas de cuerpo uterino: 50 adenocarcinomas endometrioides, 2 adenocarcinomas seroso-papilares de endometrio y 3 tumores mullerianos mixtos (TMM), tratados mediante laparoscopia asistida por robot (da Vinci) en el Hospital Universitario de Basurto desde octubre del 2009 hasta diciembre del 2011. Las variables analizadas han sido: edad, indice de masa corporal (IMC), tipos histologicos, estadios, tipos de tratamientos, medias del tiempo quirurgico, media del numero de ganglios obtenidos y numero y porcentaje de ganglios invadidos, sangrado operatorio y conversiones a laparotomia. Asi mismo, se han analizado el numero y el porcentaje de las complicaciones intraoperatorias, postoperatorias y totales. Resultados Media de ganglios pelvicos: 14,44 vs. 13,16. Tiempo operatorio: 181,1/286,5 min vs. 196,33 min. Conversion a laparotomia: 5,45% vs. 2,9%. Complicaciones totales: 16,36% vs. 6,4%. Conclusiones 1) El numero de ganglios pelvicos obtenidos y el tiempo operatorio son similares a los publicados en el estudio del AJOG; 2) la conversion a laparotomia y el porcentaje de complicaciones totales son superiores a los referidos en el estudio del AJOG, quizas debido al menor numero de casos y a la menor experiencia (curva de aprendizaje); 3) la laparoscopia asistida por robot es una via adecuada y con gran futuro en el tratamiento y la estadificacion de los carcinomas de cuerpo uterino.

Sporadic adrenomedullary hyperplasia may mimic pheochromocytoma. Laparoscopic adrenalectomy is recommended for the management of this entity., Background and Objectives: Sporadic adrenomedullary hyperplasia (AMH) is characterized by a medical history of hypertension, excessive catecholamine excretion, and histomorphometric evidence of increased adrenomedullary tissue relative to the cortex in the absence of multiple endocrine neoplasia. The aim of this study was to perform a retrospective analysis of patients after laparoscopic adrenalectomy for AMH, an early form of sporadic adrenal medulla–related endocrine hypertension, as well as to update our understanding of the clinical features and management of this clinicomorphologic entity. Methods: We performed a retrospective review of the medical records of patients operated on between 2007 and 2011 at Reina Sofia University General Hospital, Murcia, Spain, with a diagnosis of AMH. Patient characteristics, diagnostic studies, surgical procedures, and histologic findings were analyzed. Results: Seven hypertensive patients with intermittent adrenergic crises were found to have AMH (3 men and 4 women; mean age, 44 years). Catecholamine levels were increased. Radiologic studies included 1 or more of the following: magnetic resonance imaging, computed tomography, positron emission tomography imaging with fluorodeoxyglucose, dihydroxyphenylalanine–positron emission tomography–computed tomography, Octreoscan (Mallinckrodt Pharmaceuticals, St. Louis, MO, USA) and 123I-metaiodobenzylguanidine scintigraphy. Laparoscopic adrenalectomy was performed in all cases. One patient underwent bilateral adrenalectomy because of persistent symptomatology after unilateral adrenalectomy. Surgery was associated with normalization of catecholamine hypersecretion and complete disappearance of symptoms, as well as the reduction or abstention of antihypertensive therapy. Conclusions: Sporadic AMH is a clinicomorphologic entity that may mimic pheochromocytoma clinically. Recent advances in diagnostic and surgical methods have changed the management and outcome of this unusual disease. Laparoscopic adrenalectomy may be recommended as the gold standard in the treatment of this entity. Definitive diagnosis is provided by histologic study.

This is an open access article distributed under the Creative Commons Attribution License.-- et al., Ischemic stroke is an acute vascular event that obstructs blood supply to the brain, producing irreversible damage that affects neurons but also glial and brain vessel cells. Immediately after the stroke, the ischemic tissue produces nitric oxide (NO) to recover blood perfusion but also produces superoxide anion. These compounds interact, producing peroxynitrite, which irreversibly nitrates protein tyrosines. The present study measured NO production in a human neuroblastoma (SH-SY5Y), a murine glial (BV2), a human endothelial cell line (HUVEC), and in primary cultures of human cerebral myocytes (HC-VSMCs) after experimental ischemia in vitro. Neuronal, endothelial, and inducible NO synthase (NOS) expression was also studied up to 24 h after ischemia, showing a different time course depending on the NOS type and the cells studied. Finally, we carried out cell viability experiments on SH-SY5Y cells with H2O2, a prooxidant agent, and with a NO donor to mimic ischemic conditions. We found that both compounds were highly toxic when they interacted, producing peroxynitrite. We obtained similar results when all cells were challenged with peroxynitrite. Our data suggest that peroxynitrite induces cell death and is a very harmful agent in brain ischemia. © 2013 Marta Tajes et al., This work was supported by the Spanish Ministry of Science and Innovation (SAF2012-38140; SAF 2009-10365); Fondo de Investigación Sanitaria (PI10/00587; FIS CP04-00112, FIS PS09/00664 and Red HERACLES RD12/0042/0014, RD12/0042/0016 and RD12/0042/0020); FEDER Funds; Generalitat de Catalunya (SGR05-266); and Fundació la Marató de TV3 (100310). Miguel A. Valverde is the recipient of an ICREA Academia Award. Dr. Ana M. Galán belongs to the Miguel Servet stabilization program of the Spanish Government’s ISCIII research institute and “Direcció d’Estratègia i Coordinació del Departament de Salut” of the Generalitat de Catalunya.

Objetivo: Aplicar un círculo de mejora al consentimiento informado para la transfusión de hemoderivados. Pacientes y Método: Durante 10 meses se incluyeron 577 pacientes intervenidos en el Hospital General Reina Sofía de Murcia. Seleccionamos 6 criterios relacionados con el cumplimiento de la normativa sobre transfusiones. Tras el análisis de calidad, se aplicaron medidas correctoras y se reevaluaron los criterios. Los datos se compararon con los estándares en ambos periodos y entre periodos. En la primera evaluación se obtuvo un pobre cumplimiento de los criterios. Basándonos en el análisis de factores asociados al incumplimiento y la priorización resultante del diagrama de Pareto, el plan de intervención se dividió en actividad docente y modificaciones organizativas. Resultados: Todos los criterios estaban por debajo del estándar (p