The RND-family transporter, HpnN, is required for hopanoid localization to the outer membrane of Rhodopseudomonas palustris TIE-1

Rhodopseudomonas palustris TIE-1 is a Gram-negative bacterium that produces structurally diverse hopanoid lipids that are similar to eukaryotic steroids. Its genome encodes several homologues to proteins involved in eukaryotic steroid trafficking. In this study, we explored the possibility that two of these proteins are involved in intracellular hopanoid transport. R. palustris has a sophisticated membrane system comprising outer, cytoplasmic, and inner cytoplasmic membranes. It also divides asymmetrically, producing a mother and swarmer cell. We deleted genes encoding two putative hopanoid transporters that belong to the resistance–nodulation– cell division superfamily. Phenotypic analyses revealed that one of these putative transporters (HpnN) is essential for the movement of hopanoids from the cytoplasmic to the outer membrane, whereas the other (Rpal_4267) plays a minor role. C30 hopanoids, such as diploptene, are evenly distributed between mother and swarmer cells, whereas hpnN is required for the C35 hopanoid, bacteriohopanetetrol, to remain localized to the mother cell type. Mutant cells lacking HpnN grow like the WT at 30 °C but slower at 38 °C. Following cell division at 38 °C, the ΔhpnN cells remain connected by their cell wall, forming long filaments. This phenotype may be attributed to hopanoid mislocalization because a double mutant deficient in both hopanoid biosynthesis and transport does not form filaments. However, the lack of hopanoids severely compromises cell growth at higher temperatures more generally. Because hopanoid mutants only manifest a strong phenotype under certain conditions, R. palustris is an attractive model organism in which to study their transport and function

Polysialic acid sustains cancer cell survival and migratory capacity in a hypoxic environment

Polysialic acid (polySia) is a unique carbohydrate polymer expressed on the surface of NCAM (neuronal cell adhesion molecule) in a number of cancers where it modulates cell-cell and cell-matrix adhesion, migration, invasion and metastasis and is strongly associated with poor clinical prognosis. We have carried out the first investigation into the effect of polySia expression on the behaviour of cancer cells in hypoxia, a key source of chemoresistance in tumours. The role of polysialylation and associated tumour cell migration and cell adhesion were studied in hypoxia, along with effects on cell survival and the potential role of HIF-1. Our findings provide the first evidence that polySia expression sustains migratory capacity and is associated with tumour cell survival in hypoxia. Initial mechanistic studies indicate a potential role for HIF-1 in sustaining polySia-mediated migratory capacity, but not cell survival. These data add to the growing body of evidence pointing to a crucial role for the polysialyltransferases (polySTs) in neuroendocrine tumour progression and provide the first evidence to suggest that polySia is associated with an aggressive phenotype in tumour hypoxia. These results have significant potential implications for polyST inhibition as an anti-metastatic therapeutic strategy and for targeting hypoxic cancer cells

Two-channel dansyl/tryptophan emitters with a cholic acid bridge as reporters for local hydrophobicity within supramolecular systems based on bile salts

The aim of the present work is to develop two-channel emitters to probe local hydrophobicity by means of fluorescence quenching within different biomimetic supramolecular environments. To achieve this goal, the dansyl (Dns) and tryptophan (Trp) fluorophores have been covalently attached to cholic acid (CA) in order to ensure simultaneous incorporation of the two emitting units into the same compartment. In principle, the two fluorophores of the synthesized Dns-CA-Trp probes could either exhibit an orthogonal behavior or display excited state interactions. The fluorescence spectra of 3 beta-Dns-CA-Trp showed a residual Trp emission band at ca. 350 nm and an enhanced Dns maximum in the 500-550 nm region. This reveals a partial intramolecular energy transfer, which is consistent with the Dns and Trp singlet energies. Thus, the two photoactive units are not orthogonal; nevertheless, 3 beta-Dns-CA-Trp seems appropriate as a two-channel reporter for the supramolecular systems of interest. Fluorescence quenching of 3 beta-Dns-CA-Trp by iodide (which remains essentially in bulk water) was examined within sodium cholate, sodium taurocholate, sodium deoxycholate and mixed micelles. Interestingly, a decrease in the emission intensity of the two bands was observed with increasing iodide concentrations. The most remarkable effect was observed for mixed micelles, where the quenching rate constants were one order of magnitude lower than in solution. As anticipated, the quenching efficiency by iodide decreased with increasing hydrophobicity of the microenvironment, a trend that can be correlated with the relative accessibility of the probe to the ionic quencher.Financial support from the Spanish Government (CTQ2012-38754-C03-03), Predoctoral FPU fellowship (AP2008-03295), and the Generalitat Valenciana (Prometeo Program) is gratefully acknowledged.Gómez Mendoza, M.; Marín García, ML.; Miranda Alonso, MÁ. (2014). Two-channel dansyl/tryptophan emitters with a cholic acid bridge as reporters for local hydrophobicity within supramolecular systems based on bile salts. Organic and Biomolecular Chemistry. 12(42):8499-8504. https://doi.org/10.1039/c4ob01394hS849985041242Vayá, I., Lhiaubet-Vallet, V., Jiménez, M. C., & Miranda, M. A. (2014). Photoactive assemblies of organic compounds and biomolecules: drug–protein supramolecular systems. Chem. Soc. Rev., 43(12), 4102-4122. doi:10.1039/c3cs60413fGomez-Mendoza, M., Marin, M. L., & Miranda, M. A. (2011). Dansyl Derivatives of Cholic Acid as Tools to Build Speciation Diagrams for Sodium Cholate Aggregation. The Journal of Physical Chemistry Letters, 2(7), 782-785. doi:10.1021/jz200178rGomez-Mendoza, M., Marin, M. L., & Miranda, M. A. (2012). Dansyl-Labeled Cholic Acid as a Tool To Build Speciation Diagrams for the Aggregation of Bile Acids. The Journal of Physical Chemistry B, 116(51), 14776-14780. doi:10.1021/jp308624hWaissbluth, O. L., Morales, M. C., & Bohne, C. (2006). Influence of Planarity and Size on Guest Binding with Sodium Cholate Aggregates. Photochemistry and Photobiology, 82(4), 1030. doi:10.1562/2006-02-14-ra-803Rinco, O., Kleinman, M. H., & Bohne, C. (2001). Reactivity of Benzophones in the Different Binding Sites of Sodium Cholate Aggregates. Langmuir, 17(19), 5781-5790. doi:10.1021/la010526cHofmann, A. F. (1999). The Continuing Importance of Bile Acids in Liver and Intestinal Disease. Archives of Internal Medicine, 159(22), 2647. doi:10.1001/archinte.159.22.2647Nuin, E., Gómez-Mendoza, M., Andreu, I., Marin, M. L., & Miranda, M. A. (2012). New Photoactive Compounds To Probe Cholic Acid and Cholesterol inside Mixed Micelles. Organic Letters, 15(2), 298-301. doi:10.1021/ol303201yHammad, M. ., & Müller, B. . (1998). Increasing drug solubility by means of bile salt–phosphatidylcholine-based mixed micelles. European Journal of Pharmaceutics and Biopharmaceutics, 46(3), 361-367. doi:10.1016/s0939-6411(98)00037-xHammad, M. ., & Müller, B. . (1998). Solubility and stability of tetrazepam in mixed micelles. European Journal of Pharmaceutical Sciences, 7(1), 49-55. doi:10.1016/s0928-0987(98)00006-2Hammad, M. (1998). Solubility and stability of clonazepam in mixed micelles. International Journal of Pharmaceutics, 169(1), 55-64. doi:10.1016/s0378-5173(98)00117-3Hendradi, E., Obata, Y., Isowa, K., Nagai, T., & Takayama, K. (2003). Effect of Mixed Micelle Formulations Including Terpenes on the Transdermal Delivery of Diclofenac. Biological & Pharmaceutical Bulletin, 26(12), 1739-1743. doi:10.1248/bpb.26.1739Parsaee, S., Sarbolouki, M. N., & Parnianpour, M. (2002). In-vitro release of diclofenac diethylammonium from lipid-based formulations. International Journal of Pharmaceutics, 241(1), 185-190. doi:10.1016/s0378-5173(02)00238-7Yu, J., Zhu, Y., Wang, L., Peng, M., Tong, S., Cao, X., … Xu, X. (2010). Enhancement of oral bioavailability of the poorly water-soluble drug silybin by sodium cholate/phospholipid-mixed micelles. Acta Pharmacologica Sinica, 31(6), 759-764. doi:10.1038/aps.2010.55Sznitowska, M., Klunder, M., & Placzek, M. (2008). Paclitaxel Solubility in Aqueous Dispersions and Mixed Micellar Solutions of Lecithin. CHEMICAL & PHARMACEUTICAL BULLETIN, 56(1), 70-74. doi:10.1248/cpb.56.70Nuin, E., Gomez-Mendoza, M., Marin, M. L., Andreu, I., & Miranda, M. A. (2013). Influence of Drug Encapsulation within Mixed Micelles on the Excited State Dynamics and Accessibility to Ionic Quenchers. The Journal of Physical Chemistry B, 117(32), 9327-9332. doi:10.1021/jp404353uCuquerella, M. C., Rohacova, J., Marin, M. L., & Miranda, M. A. (2010). Stereodifferentiation in fluorescence quenching within cholic acid aggregates. Chemical Communications, 46(27), 4965. doi:10.1039/c0cc00176gWu, J., Liu, W., Ge, J., Zhang, H., & Wang, P. (2011). New sensing mechanisms for design of fluorescent chemosensors emerging in recent years. Chemical Society Reviews, 40(7), 3483. doi:10.1039/c0cs00224kBronshtein, I., Afri, M., Weitman, H., Frimer, A. A., Smith, K. M., & Ehrenberg, B. (2004). Porphyrin Depth in Lipid Bilayers as Determined by Iodide and Parallax Fluorescence Quenching Methods and Its Effect on Photosensitizing Efficiency. Biophysical Journal, 87(2), 1155-1164. doi:10.1529/biophysj.104.041434Rohacova, J., Marin, M. L., Martínez-Romero, A., O’Connor, J.-E., Gomez-Lechon, M. J., Donato, M. T., … Miranda, M. A. (2009). Synthesis of new, UV-photoactive dansyl derivatives for flow cytometric studies on bile acid uptake. Organic & Biomolecular Chemistry, 7(23), 4973. doi:10.1039/b912134jFőrster, T. (1959). 10th Spiers Memorial Lecture. Transfer mechanisms of electronic excitation. Discuss. Faraday Soc., 27(0), 7-17. doi:10.1039/df9592700007Eaton, D. F. (1988). Reference materials for fluorescence measurement. Pure and Applied Chemistry, 60(7), 1107-1114. doi:10.1351/pac198860071107T. Förster , Modern Quantum Chemistry , Academic Press , New York , 196

Inverse-probability weighting and multiple imputation for evaluating selection bias in the estimation of childhood obesity prevalence using data from electronic health records

Background and objectives: Height and weight data from electronic health records are increasingly being used to estimate the prevalence of childhood obesity. Here, we aim to assess the selection bias due to missing weight and height data from electronic health records in children older than five. Methods: Cohort study of 10,811 children born in Navarra (Spain) between 2002 and 2003, who were still living in this region by December 2016. We examined the differences between measured and non-measured children older than 5 years considering weight-associated variables (sex, rural or urban residence, family income and weight status at 2–5 yrs). These variables were used to calculate stabilized weights for inverse-probability weighting and to conduct multiple imputation for the missing data. We calculated complete data prevalence and adjusted prevalence considering the missing data using inverse-probability weighting and multiple imputation for ages 6 to 14 and group ages 6 to 9 and 10 to 14. Results: For 6–9 years, complete data, inverse-probability weighting and multiple imputation obesity age-adjusted prevalence were 13.18% (95% CI: 12.54–13.85), 13.22% (95% CI: 12.57–13.89) and 13.02% (95% CI: 12.38–13.66) and for 10–14 years 8.61% (95% CI: 8.06–9.18), 8.62% (95% CI: 8.06–9.20) and 8.24% (95% CI: 7.70–8.78), respectively. Conclusions: Ages at which well-child visits are scheduled and for the 6 to 9 and 10 to 14 age groups, weight status estimations are similar using complete data, multiple imputation and inverse-probability weighting. Readily available electronic health record data may be a tool to monitor the weight status in children

Asymptomatic and Submicroscopic Carriage of Plasmodium knowlesi Malaria in Household and Community Members of Clinical Cases in Sabah, Malaysia

Although asymptomatic carriage of human malaria species has been widely reported, the extent of asymptomatic, submicroscopic Plasmodium knowlesi parasitemia is unknown. In this study, samples were obtained from individuals residing in households or villages of symptomatic malaria cases with the aim of detecting submicroscopic P. knowlesi in this population. Four published molecular assays were used to confirm the presence of P. knowlesi. Latent class analysis revealed that the estimated proportion of asymptomatic individuals was 6.9% (95% confidence interval, 5.6%-8.4%). This study confirms the presence of a substantial number of asymptomatic monoinfections across all age groups; further work is needed to estimate prevalence in the wider community

Fluoroquinolone photodegradation influences specific basophil activation

Fluoroquinolones (FQs) are photoreactive drugs, but it is not known whether laboratory light exposure can influence the induction of photoproducts and modify in vitro test results. The basophil activation test (BAT) has proven to be useful for evaluating immunoglobulin E (IgE)-mediated hypersensitivity to FQs, with a higher percentage of positive responders with ciprofloxacin (CIP) than with moxifloxacin (MOX). We studied the effect of laboratory light on CIP and MOX degradation, and drug-protein conjugate formation, and its influence on the BAT for evaluating IgE-mediated hypersensitivity to FQs. The results showed an important decrease in fluorescence emission intensity under light compared to dark conditions for MOX, and that BAT positivity was lower in light (17.9%) than in dark (35.7%) conditions. No changes were found for CIP in either fluorescence emission intensity or BAT results (46.4% in both conditions). We can conclude that light exposure is a critical factor in BAT results when photolabile drugs like MOX are used. Therefore, light is important when interpreting in vitro results. Copyright (C) 2012 S. Karger AG, BaselWe thank Ian Johnstone for his help with the English language version of the manuscript, and Jose Luis Rodriguez-Bada and Lidia Melendez for their technical support. This study was funded by the FIS-Thematic Networks and Co-operative Research Centres: RIRAAF (RD07/0064) and the Spanish Health Ministry (FIS PS09/01768, PI11/01416 and M Servet contract CP11/00154 for I.A.), the Andalusia Health Ministry (PI-0545-2010), and the Andalusia Economic Innovation and Science Ministry (CTS 06603).Mayorga, C.; Andreu Ros, MI.; Aranda, A.; Doña, I.; Montañez, MI.; Blanca-López, N.; Ariza, A.... (2013). Fluoroquinolone photodegradation influences specific basophil activation. International Archives of Allergy and Immunology. 160(4):377-382. https://doi.org/10.1159/000343023S3773821604Albini, A., & Monti, S. (2003). Photophysics and photochemistry of fluoroquinolones. Chemical Society Reviews, 32(4), 238. doi:10.1039/b209220bBelvedere, A., Boscá, F., Cuquerella, M. C., de Guidi, G., & Miranda, M. A. (2002). Photoinduced N-Demethylation of Rufloxacin and its Methyl Ester Under Aerobic Conditions¶. Photochemistry and Photobiology, 76(3), 252. doi:10.1562/0031-8655(2002)0762.0.co;2Dawe, R. S., Ibbotson, S. H., Sanderson, J. B., Thomson, E. M., & Ferguson, J. (2003). A randomized controlled trial (volunteer study) of sitafloxacin, enoxacin, levofloxacin and sparfloxacin phototoxicity. British Journal of Dermatology, 149(6), 1232-1241. doi:10.1111/j.1365-2133.2003.05582.xHayashi, N., Nakata, Y., & Yazaki, A. (2004). New Findings on the Structure-Phototoxicity Relationship and Photostability of Fluoroquinolones with Various Substituents at Position 1. Antimicrobial Agents and Chemotherapy, 48(3), 799-803. doi:10.1128/aac.48.3.799-803.2004Van Bambeke, F., & Tulkens, P. M. (2009). Safety Profile of the Respiratory Fluoroquinolone Moxifloxacin. Drug Safety, 32(5), 359-378. doi:10.2165/00002018-200932050-00001Sachs, B., Riegel, S., Seebeck, J., Beier, R., Schichler, D., Barger, A., … Erdmann, S. (2006). Fluoroquinolone-Associated Anaphylaxis in Spontaneous Adverse Drug Reaction Reports in Germany. Drug Safety, 29(11), 1087-1100. doi:10.2165/00002018-200629110-00008Manfredi, M., Severino, M., Testi, S., Macchia, D., Ermini, G., Pichler, W. J., & Campi, P. (2004). Detection of specific IgE to quinolones. Journal of Allergy and Clinical Immunology, 113(1), 155-160. doi:10.1016/j.jaci.2003.09.035Aranda, A., Mayorga, C., Ariza, A., Doña, I., Rosado, A., Blanca-Lopez, N., … Torres, M. J. (2010). In vitro evaluation of IgE-mediated hypersensitivity reactions to quinolones. Allergy, 66(2), 247-254. doi:10.1111/j.1398-9995.2010.02460.xAndreu, I., Mayorga, C., & Miranda, M. A. (2010). Generation of reactive intermediates in photoallergic dermatitis. Current Opinion in Allergy and Clinical Immunology, 10(4), 303-308. doi:10.1097/aci.0b013e32833bc68cAntunez, C., Fernandez, T., Blanca-Lopez, N., Torres, M. J., Mayorga, C., Canto, G., … Blanca, M. (2006). IgE antibodies to betalactams: relationship between the triggering hapten and the specificity of the immune response. Allergy, 61(8), 940-946. doi:10.1111/j.1398-9995.2006.01120.xTorres, M. J., Ariza, A., Mayorga, C., Doña, I., Blanca-Lopez, N., Rondon, C., & Blanca, M. (2010). Clavulanic acid can be the component in amoxicillin-clavulanic acid responsible for immediate hypersensitivity reactions. Journal of Allergy and Clinical Immunology, 125(2), 502-505.e2. doi:10.1016/j.jaci.2009.11.032Torres, M. J., & Blanca, M. (2010). The Complex Clinical Picture of β-Lactam Hypersensitivity: Penicillins, Cephalosporins, Monobactams, Carbapenems, and Clavams. Medical Clinics of North America, 94(4), 805-820. doi:10.1016/j.mcna.2010.04.00

Recomendaciones de prevención del cáncer. Actualización 2016

En este artículo presentamos una nueva actualización de las recomendaciones sobre prevención y cribados del cáncer del Grupo de Prevención del Cáncer del Programa de Prevención y Promoción de la Salud (PAPPS) de la Sociedad Española de Medicina Familiar y Comunitaria (semFYC). Para la síntesis de la evidencia y la formulación de las recomendaciones hemos utilizado el sistema GRADE (Grading of Recommendations Assessment, Development and Evaluation). GRADE define la fuerza de una recomendación en términos de la confianza que tenemos en que los desenlaces deseados de una intervención (p. ej., los beneficios) sean superiores a los indeseados (p. ej., los inconvenientes y los efectos adversos). En una recomendación a favor, los efectos deseados de una intervención frente a otra superan a los no deseados. En una recomendación en contra, los efectos no deseados superan a los efectos deseados. Ambas recomendaciones pueden ser a su vez fuertes, cuando podemos confiar en que habrá un balance favorable entre efectos deseados y no deseados de una intervención frente a otra, o, por el contrario, débiles, si hay incertidumbre sobre ese balance. Para elaborar las recomendaciones se ha tenido en cuenta la calidad de la evidencia científica, el balance entre beneficios y riesgos, el riesgo basal, los valores y preferencias de las personas y los costes. Las recomendaciones se han valorado desde la perspectiva individual y poblacional. Las personas deben estar informadas de los beneficios y riesgos del cribado. Los valores y preferencias personales son clave a la hora de tomar una decisión: algunas personas le darán mucho valor a los posibles beneficios (p. ej., reducción de la mortalidad), pero otras querrán evitar los riesgos del sobrediagnóstico y sobretratamiento y los posibles perjuicios sobre su calidad de vida. Las recomendaciones propuestas tienen como referencia las revisiones de la US Preventive Services Task Force (USPSTF) y la Canadian Task Force (CTF) instituciones de referencia en la elaboración de recomendaciones de prevención en el contexto de la atención primaria (AP), y el National Institute for Health and Care Excellence (NICE). Las recomendaciones sobre cribados de cáncer de la USPSTF se pueden consultar en el monográfico de 2014. La USPSTF actualmente está revisando las recomendaciones de cáncer de mama, cuello uterino, próstata y cáncer de piel5. Todas estas instituciones siguen o han adaptado la metodología propuesta por GRADE. Asimismo, se ha tenido en cuenta las directrices de la Estrategia de Cáncer del Sistema Nacional de Salud (SNS), actualmente en proceso de revisión

Recomendaciones de prevención del cáncer. Actualización PAPPS 2018

La comisión del Lancet Oncology, integrada por médicos e investigadores de atención primaria (AP), sobre la base de la evidencia científica y argumentos amplios y exhaustivos, ha elaborado un informe sobre la importancia cada vez mayor de la AP en el control del cáncer, desde la prevención hasta el seguimiento después del tratamiento, o en la atención de final de vida1. El informe de la comisión señala la necesidad de modelos de atención integrados, coordinados y acordados entre niveles asistenciales1. En la figura 1 se presenta, a modo de ejemplo, el modelo compartido propuesto por el Cancer Care Manitoba de Canadá2. Destaca la influencia de los profesionales de AP en facilitar estrategias de prevención dirigidas a modificar los estilos de vida y factores de riesgo de cáncer conocidos1. También señala que, cuando los médicos de familia se involucran en los programas de cribado, las tasas de participación aumentan1. Otro elemento en el que incide el informe es en que, para conseguir un diagnóstico de cáncer más precoz, el médico de familia debe tener un mejor acceso a las pruebas diagnósticas y disponer de herramientas de apoyo a las decisiones clínicas a través de la historia clínica informatizada1. Asimismo, apunta la necesidad de ofrecer una atención holística integral que cubra las consecuencias físicas y psicológicas de las personas que han sobrevivido al cáncer. En este artículo, el grupo de Prevención del Cáncer del Programa de Prevención y Promoción de la Salud (PAPPS) de la Sociedad Española de Medicina Familiar y Comunitaria (semFYC)3 actualiza las evidencias y recomendaciones sobre prevención y detección precoz del cáncer en población de riesgo medio y de riesgo elevado. Para clasificar la calidad de la evidencia y la fuerza de las recomendaciones, se ha utilizado el sistema GRADE (Grading of Recommendations Assessment, Development and Evaluation

Photoactive bile salts with critical micellar concentration in the micromolar range

The aggregation behavior of bile salts is strongly dependent on the number of hydroxyl groups. Thus, cholic acid (CA), with three hydroxyls, starts forming aggregates at 15 mM, while deoxycholic, chenodeoxycholic or ursodeoxycholic acids, with two hydroxyls, start aggregating at 5-10 mM; for lithocholic acid, with only one hydroxyl group, aggregation is observed at lower concentration (2-3 mM). Here, the singular self-assembling properties of dansyl and naproxen derivatives of CA (3 beta-Dns-CA and 3 beta-NPX-CA, respectively) have been demonstrated on the basis of their photoactive properties. Thus, the emission spectra of 3 beta-Dns-CA registered at increasing concentrations (25-140 mu M) showed a remarkable non-linear enhancement in the emission intensity accompanied by a hypsochromic shift of the maximum and up to a three-fold increase in the singlet lifetime. The inflection point at around 50-70 mu M pointed to the formation of unprecedented assemblies at such low concentrations. In the case of 3 beta-NPX-CA, when the NPX relative triplet lifetime was plotted against concentration, a marked increase (up to two-fold) was observed at 40-70 mu M, indicating the formation of new 3 beta-NPX-CA assemblies at ca. 50 mu M. Additional evidence supporting the formation of new 3 beta-Dns-CA or 3 beta-NPX-CA assemblies at 40-70 mu M was obtained from singlet excited state quenching experiments using iodide. Moreover, to address the potential formation of hybrid assemblies, 1 : 1 mixtures of 3 beta-Dns-CA and 3 beta-NPX-CA (2-60 mu M, total concentration) were subjected to steady-state fluorescence experiments, and their behavior was compared to that of the pure photoactive derivatives. A lower increase in the emission was observed for 3 beta-NPX-CA in the mixture, while a huge increase was experienced by 3 beta-Dns-CA in the same concentration range (up to 60 mu M total). A partial intermolecular energy transfer from NPX to Dns, consistent with their reported singlet energies, was revealed, pointing to the formation of extremely fluorescent hybrid assemblies at 5-10 mu M (total concentration). The morphology of the entities was investigated by means of confocal microscopy. At 90 mu M, 3 beta-Dns-CA showed disperse assemblies in the mu m range.Financial support from the Spanish Government (Grants SEV-2012-0267 and CTQ2012-38754-C03-03) and the Generalitat Valenciana (Prometeo Program) is gratefully acknowledged.Gómez Mendoza, M.; Marín García, ML.; Miranda Alonso, MÁ. (2016). Photoactive bile salts with critical micellar concentration in the micromolar range. Physical Chemistry Chemical Physics. 18(18):12976-12982. https://doi.org/10.1039/c6cp00813eS1297612982181

ESPACIO EUROPEO DE EDUCACIÓN SUPERIOR. Situación actual. Marco legislativo.

Nowadays the number of nursing schools including in their study plans the Practicum subjects are increasing. These subjects are devoted to clinical practice and the majority of practical credits belonging to clinical subjects are concentrated on them. The reasons for it are that these subjects link the learning methodology proposed by the European Space for Higher Education. In the present work, which is a continuation of a previous one published in this journal, we propose a Teaching Project to give the Medical-Surgical Nursing clinical practicum of the study plans for the Registered Nursing degree. Following the same structure of our previous work, we propose a methodology based on the teaching of competences. The program and the system of credits are in line with the ancient Law of University Reform but they are also compatible with convergent method of the European Space for Higher Education. In the same way, we chose this subject on the grounds of its high credit load on the current study plans (being clinical the majority of them). All this make that steps to achieve convergence for this subject could be used for other nursing subject.El objetivo de este artículo es realizar un análisis de la legislación actual y la repercusión del cambio ya iniciado en algunas titulaciones como es el caso de Enfermería en el marco académico de la Educación Superior, reforma importante del Sistema Universitario Español. Para ello se revisa el contenido y análisis de la documentación publicada en el Ministerio de Educación relativa a Educación Superior; la legislación vigente española y la legislación Comunitaria con objeto de aproximar la legislación al marco de los estudios de enfermería