Migration through a Major Andean Ecogeographic Disruption as a Driver of Genetic and Phenotypic Diversity in a Wild Tomato Species.

Evolutionary dynamics at the population level play a central role in creating the diversity of life on our planet. In this study, we sought to understand the origins of such population-level variation in mating systems and defensive acylsugar chemistry in Solanum habrochaites-a wild tomato species found in diverse Andean habitats in Ecuador and Peru. Using Restriction-site-Associated-DNA-Sequencing (RAD-seq) of 50 S. habrochaites accessions, we identified eight population clusters generated via isolation and hybridization dynamics of 4-6 ancestral populations. Detailed characterization of mating systems of these clusters revealed emergence of multiple self-compatible (SC) groups from progenitor self-incompatible populations in the northern part of the species range. Emergence of these SC groups was also associated with fixation of deleterious alleles inactivating acylsugar acetylation. The Amotape-Huancabamba Zone-a geographical landmark in the Andes with high endemism and isolated microhabitats-was identified as a major driver of differentiation in the northern species range, whereas large geographical distances contributed to population structure and evolution of a novel SC group in the central and southern parts of the range, where the species was also inferred to have originated. Findings presented here highlight the role of the diverse ecogeography of Peru and Ecuador in generating population differentiation, and enhance our understanding of the microevolutionary processes that create biological diversity.

Enzyme/Nanocopper Hybrid Nanozymes: Modulating Enzyme-like Activity by the Protein Structure for Biosensing and Tumor Catalytic Therapy.

Artificial enzymes with modulated enzyme-mimicking activities of natural systems represent a challenge in catalytic applications. Here, we show the creation of artificial Cu metalloenzymes based on the generation of Cu nanoparticles in an enzyme matrix. Different enzymes were used, and the structural differences between the enzymes especially influenced the controlled the size of the nanoparticles and the environment that surrounds them. Herein, we demonstrated that the oxidase-like catalytic activity of these copper nanozymes was rationally modulated by enzyme used as a scaffold, with a special role in the nanoparticle size and their environment. In this sense, these nanocopper hybrids have confirmed the ability to mimic a unique enzymatic activity completely different from the natural activity of the enzyme used as a scaffold, such as tyrosinase-like activity or as Fenton catalyst, which has extremely higher stability than natural mushroom tyrosinase. More interestingly, the oxidoreductase-like activity of nanocopper hybrids was cooperatively modulated with the synergistic effect between the enzyme and the nanoparticles improving the catalase activity (no peroxidase activity). Additionally, a novel dual (metallic and enzymatic activity) of the nanozyme made the highly improved catechol-like activity interesting for the design of 3,4-dihydroxy-l-phenylalanine (l-DOPA) biosensor for detection of tyrosinase. These hybrids also showed cytotoxic activity against different tumor cells, interesting in biocatalytic tumor therapy.

Vitamin D increases remyelination by promoting oligodendrocyte lineage differentiation.

INTRODUCTION: Several experimental studies have suggested the potential remyelinating effects of vitamin D (VitD) supplements regardless of the presence of VitD deficiency. This study aims to analyze neurogenesis in a model of toxic demyelination in order to evaluate the effects of VitD on demyelination and remyelination. MATERIAL AND METHODS: We used 24 male Wistar rats that had received surgical lesions to the corpus callosum and were injected with lysolecithin. Rats were divided into three groups: Group 1 included eight rats with lesions to the corpus callosum but not lysolecithin injections (sham group), group 2 included eight rats with lesions to the corpus callosum that were injected with lysolecithin (lysolecithin group), and group 3 included eight rats with lesions that were injected with lysolecithin and received VitD (VitD group). We analyzed neurogenesis both in the subventricular zone and at the lesion site. RESULTS: Administration of VitD promotes the proliferation and differentiation of neural stem cells in the subventricular zone and the migration of these cells to the lesion site in the corpus callosum; these cells subsequently differentiate into oligodendrocyte lineage cells and produce myelin basic protein. This phenomenon was not caused by microglial activation, which was less marked in rats receiving VitD. Megalin expression did not increase at the lesion site, which suggests that VitD is internalized by other mechanisms. CONCLUSION: Our results support the hypothesis that regardless of the presence of VitD deficiency, treatment with VitD may contribute to remyelination by promoting the proliferation of oligodendrocyte precursor cells.

Medicina herbal china ofertada en páginas web en español: calidad de la información y riesgos / Information quality and health risks in Spanish-language retail websites for Chinese herbal medicine

Objetivo: El auge de la venta en Internet propicia el acceso a productos naturales potencialmente tóxicos y la rápida difusión de la información, no necesariamente veraz, que los proveedores ofrecen al consumidor acerca de sus propiedades. El objetivo del presente trabajo ha sido analizar en páginas web en español de venta de medicina herbal china la calidad de la información ofrecida al consumidor y los posibles riesgos derivados de su consumo. Métodos: I) Búsqueda en Google España de sitios web de venta de medicina herbal china y posterior evaluación de la información sobre las propiedades y consumo seguro de los productos ofertados. II) Identificación en los sitios web de plantas III) Cuantificación de las retiradas de productos de medicina herbal china por la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS). Resultados: 1) Sólo un tercio de las 30 páginas web localizadas cumple con la legislación vigente, ya que las demás incluyen indicaciones terapéuticas occidentales como reclamo para la venta de medicina herbal china en España 2) Cinco páginas aportan información sobre consumo seguro 3) Dos páginas ofertan plantas potencialmente tóxicas y 4) Un importante porcentaje de productos retirados por la AEMPS corresponde a medicina herbal china adulterada con sibutramina, sildenafilo o sus derivados. Conclusión: Nuestros resultados indican que existen motivos suficientes que aconsejan la creación por parte de las autoridades españolas de un sitio web que asesore a quienes pretenden utilizar Internet para comprar medicina herbal china y así permitir que los usuarios tomen decisiones estando bien informados (AU)

Objective: The growing use of purchase online via Internet retailers favours the access to potentially toxic natural products. It also contributes to the quick dissemination of the claims made by the retailers on efficacy and safety, these claims being not always based upon reliable information. Here, we have conducted an online search to find Spanish-language retail websites for Chinese herbal medicine and we have analysed them for the quality of product information and the potential health risks. Methods: I) Online search in Google España to find Spanish-language retail websites for Chinese herbal medicine in which we analysed both the claims regarding possible health benefits and adequate safe use indications II) Identification of potentially toxic herbs in the websites III) Quantification of Chinese herbal medicines withdrawn by the Agencia Española de Medicamentos y Productos Sanitarios (AEMPS). Results: 1) Only one third of the 30 Spanish-language retail websites found which sell Chinese herbal medicine observe the law, given that the other websites include illegal Western disease claims as marketing tools, 2) Five websites provide some safety information, 3) Two websites offer potentially toxic herbs and 4) Chinese herbal medicine adulterated with sibutramine, silfenafil or their analogues make a considerable percentage of the total products withdrawn by the AEMPS. Conclusion: Online health seekers should be warned about misinformation on retail websites for Chinese herbal medicine and directed to a Spanish government Web site for guidance in safely navigating the Internet for buying Chinese herbal medicine (AU)

[Information quality and health risks in Spanish-language retail websites for Chinese herbal medicine]. / Medicina herbal china ofertada en páginas web en español: calidad de la información y riesgos.

OBJECTIVE: The growing use of purchase online via Internet retailers favours the access to potentially toxic natural products. It also contributes to the quick dissemination of the claims made by the retailers on efficacy and safety, these claims being not always based upon reliable information. Here, we have conducted an online search to find Spanish-language retail websites for Chinese herbal medicine and we have analysed them for the quality of product information and the potential health risks. METHODS: i) Online search in Google España to find Spanish-language retail websites for Chinese herbal medicine in which we analysed both the claims regarding possible health benefits and adequate safe use indications ii) Identification of potentially toxic herbs in the websites iii) Quantification of Chinese herbal medicines withdrawn by the Agencia Española de Medicamentos y Productos Sanitarios (AEMPS). RESULTS: 1) Only one third of the 30 Spanish-language retail websites found which sell Chinese herbal medicine observe the law, given that the other websites include illegal Western disease claims as marketing tools, 2) Five websites provide some safety information, 3) Two websites offer potentially toxic herbs and 4) Chinese herbal medicine adulterated with sibutramine, silfenafil or their analogues make a considerable percentage of the total products withdrawn by the AEMPS. CONCLUSION: Online health seekers should be warned about misinformation on retail websites for Chinese herbal medicine and directed to a Spanish government Web site for guidance in safely navigating the Internet for buying Chinese herbal medicine.

Miastenia gravis y maternidad / Myasthenia gravis and pregnancy

OBJETIVOS: Conocer el imaginario de las mujeres embarazadas sobre la maternidad. MATERIAL Y MÉTODO: Estudio llevado a cabo con metodología cualitativa. La información se generó mediante entrevistas semiestructuradas y se realizó un análisis sociológico de los discursos. Los sujetos de estudio fueron 10 mujeres embarazadas de 36-37 semanas de gestación. Se atendió a los aspectos éticos y legales. RESULTADOS: La decisión de ser madre es, en ocasiones, poco explícita: la maternidad aparece como destino femenino, enaltecida por ser fuente de nuevas experiencias y satisfacciones, pero también relacionada con un aumento de las obligaciones y las responsabilidades, con las consiguientes repercusiones en la vida personal y laboral. Las mujeres expresan inseguridad e incertidumbre ante el nuevo papel requerido: el de madre. El instinto maternal aparece en el imaginario de las mujeres, pero no el paternal. CONCLUSIONES: La fuerte asociación entre maternidad e identidad femenina en el orden cultural y simbólico hegemónico actúa como motor en la decisión de ser madre. El instinto maternal aparece en el imaginario de las mujeres para dar una explicación naturalista al rol de madre. Surge la preocupación acerca de las estrategias necesarias para conciliar la vida laboral con la familiar: las renuncias laborales están relacionadas con la naturalización del rol de madre. La maternidad es una experiencia individual contextualizada en un entorno social, cultural, histórico, económico y laboral. Estudiar las creencias y los valores de una sociedad androcéntrica nos permitirá conocer las interacciones que se dan en ella, y reconocer a las mujeres como agentes capaces de construir nuevos significados. Una madre no nace, se hace

OBJECTIVES: To know how pregnancy, delivery and postpartum period are affected by myasthenia gravis and to analyze the management of the disease during this period. METHODS: A bibliographic search has been done in CINAHL, PubMed, Science Direct, Scopus, Proquest, Lilacs, Scielo, Cochrane Plus, Cuiden Plus and IME databases. RESULTS: We have chosen 40 articles. Myasthenia in pregnancy is associated to an increased risk of preterm delivery, premature ruptured membranes and neonatal mortality. Instrumental labor is recommended to avoid maternal weakness. Breastfeeding is not contraindicated if maternal disease is well-controlled. CONCLUSIONS: Myasthenia gravis increases the risk of complications during this period. Pregnancy has to be planned in advance. Fetal monitoring is essential

Ortogeriatría: primer registro multicéntrico autonómico de fracturas de cadera en Castilla y León (España) / Orthogeriatrics: The First multicentre regional register of hip fractures in Castilla y León (Spain)

Objetivo: El objetivo de este trabajo es describir las características de los pacientes con fractura de cadera en los hospitales públicos de Castilla y León recogidos durante un periodo de tiempo de 3 meses (noviembre del 2014 y octubre y noviembre del 2015). Material y método: El grupo de trabajo de Ortogeriatría de Castilla y León elabora un registro común para recoger datos de las fracturas de cadera. Se incluyen mayores de 74 años ingresados por fractura de cadera, en 13 hospitales públicos de la comunidad, los meses de noviembre del 2014 y octubre-noviembre del 2015. Es un estudio multicéntrico, prospectivo y observacional en el que se recogieron variables clínicas, funcionales, sociales y mortalidad intrahospitalaria. Resultados: Se analizaron 776 pacientes, con una edad media de 86,6±6 años. La demora quirúrgica fue de 4±2,8 días y la estancia media hospitalaria de 10±4,7 días. El riesgo anestésico fue ASA 3±0,6. El 66,5% de los pacientes tuvieron complicaciones médicas intrahospitalarias y precisaron transfusión el 55,5%. Fallecieron durante la hospitalización un 4,6%. La estancia media prequirúrgica se relacionó con la estancia global, con p<0,001. Conclusiones: Los registros de fractura de cadera son una herramienta esencial para evaluar el proceso y mejorar la calidad asistencial de estos pacientes. Este es el primer registro multicéntrico de fracturas de cadera en ancianos realizado en una región de España y puede ser un buen precedente de referencia ante el futuro registro nacional (AU)

Objective: The objective of this study is to describe the characteristics of the patients with hip fracture admitted to the Public Hospitals of Castilla y León during three monthly periods (November 2014, and October and November 2015). Material and method: The Castilla y León orthogeriatrics work group created a common register to collect data on hip fractures. The study included patients 75 years-old and over hospitalised with hip fractures in the 13 public hospitals in the community during November 2014, and October and November 2015. A multicentre, prospective, and observational study was conducted, in which clinical, functional, and social variables, as well as in-hospital mortality, were collected. Results: The analysis included data from a total of 776 patients with a mean age of 86 (±6) years. The surgical delay was 4±2.8 days, and the mean hospital stay was 10±4.7 days. The anaesthesia risk was ASA 3±0.6. Around two-thirds (66.5%) of the patients had medical complications while in hospital, and 55.5% required a transfusion. In-hospital mortality was 4.6%. The mean pre-surgical stay was related to the overall stay: P<.001. Conclusions: Hip fracture registers are an essential tool for evaluating the process and for improving the treatment quality of these patients. This is the first multicentre register of hip fracture in the elderly created in a Spanish region, and could be a good precedent reference for a future national register (AU)

Utilidad de una vía clínica en el manejo del anciano con fractura de cadera / Clinical pathway for hip fracture patients

Introducción. La fractura de cadera del anciano se asocia con elevada comorbilidad, por lo que requiere un enfoque integral y multidisciplinar. Objetivo. Evaluar el efecto de una intervención de mejora de calidad en la detección y tratamiento de complicaciones del anciano que ingresa por fractura de cadera. Material y métodos. Estudio comparativo entre dos cohortes de pacientes ingresados por fractura de cadera antes (2010) y después de instaurar una vía clínica (2013). La intervención consistió en la implantación de protocolos para el manejo de los problemas más prevalentes, según la evidencia científica actual y se evaluó el grado de cumplimiento de las medidas implementadas. Resultados. Las características de los pacientes ingresados por fractura de cadera en 2010 (216 pacientes) y 2013 (196 pacientes) fueron similares en edad, sexo, índice de Barthel e índice de Charlson abreviado, aunque con mayor número de comorbilidades en el 2013. Tras la implantación de los protocolos, se incrementó la detección de delirium, desnutrición, anemia y trastornos electrolíticos, aumentando la prescripción de hierro por vía intravenosa (en un 24%) y de tratamiento para la osteoporosis (61,3%). La estancia media se redujo un 45,3% y la demora quirúrgica un 29,4%, consiguiéndose una mejor eficiencia funcional. Conclusión. La aplicación de una vía clínica en el proceso asistencial del paciente geriátrico con fractura de cadera es útil no solo para detectar y tratar de forma precoz las complicaciones sino también para reducir la estancia prequirúrgica y global, todo ello sin repercusión negativa en el aspecto clínico y funcional (AU)

Introduction. Hip fracture in the elderly often occurs in patients with high co-morbidity. Effective management requires a comprehensive and multidisciplinary approach. Purpose. To evaluate the effect of a quality improvement intervention in the detection and treatment of complications in elderly patients admitted for hip fracture. Material and methods. A comparative study was conducted between two groups of patients admitted for hip fracture prior to 2010, and after a quality improvement intervention in 2013. The intervention consisted of implementing improved multidisciplinary measures in accordance with recent scientific evidence. The degree of compliance of the implemented measures was quantified. Results. Patients admitted due to hip fracture in 2010 (216 patients) and 2013 (196 patients) were similar in age, sex, Barthel Index, and a reduced Charlson Index, although there were more comorbidities in 2013. After implementation of the protocols, the detection of delirium, malnutrition, anemia, and electrolyte disturbances increased. A larger number of patients in 2013 were precribed intravenous iron (24% more) and osteoporosis treatment (61.3% more). The average stay was reduced by 45.3% and surgical delay by 29.4%, achieving better functional efficiency. Conclusion. The implementation of a clinical pathway in geriatric patients with hip fracture is useful to detect and treat complications at an early stage, and to reduce pre-operative and overall stay, all without a negative clinical or functional impact (AU)

The effect of the European traditional use directive on the register of herbal medicinal products in Spain / Efecto en España de la directiva Europea de uso tradicional sobre el registro de medicamentos a base de plantas

Background: Directive 2004/24/EC, which came into force in 2011, created new regulatory requirements for traditional herbal medicines (THM). This study compared the Spanish THM registry before and after the Directive came fully into force in 2011. Methods: We consulted the herbal medicinal plant and drug catalogues (General Council of the Official Colleges of Pharmacists), the website of the European Medicines Agency (EMA), and retail web sites. Results: Of 315 THM (from 39 companies) licensed in Spain in 2010, only 48 (10 companies) remained licensed in 2013, mainly due to their withdrawal: the EMA had received just 123 applications from Spain and at least 34% formerly licensed THM had shifted to the less strictly regulated food sector, while up to 54% might have disappeared from the market. However, there is still a significant presence of retail websites making illegal health claims. Conclusion: In Spain, the public health benefits of the Directive 2004/24/EC might be less than expected (AU)

Antecedentes: En 2011 entró totalmente en vigor la Directiva 2004/24/CE, que impone nuevos requerimientos a los medicamentos tradicionales a base de plantas. Este trabajo analiza el efecto sobre su registro en España. Métodos: Se consultaron los catálogos de plantas medicinales y de medicamentos (CGCOF), la página web de la Agencia Europea del Medicamento (EMA) y sitios de venta en Internet. Resultados: De los 315 medicamentos a base de plantas autorizados en 2010, procedentes de 39 compañías; solo quedaban 48 (10 compañías) en 2013 por renuncia de la mayoría: sólo 123 solicitudes fueron recibidas a la EMA y al menos un 34% se pasó al sector de alimentación (menos estrictamente regulado). Hasta un 54% podría no comercializarse actualmente. Sin embargo, existe una presencia significativa de sitios web anunciando ilegalmente propiedades saludables para sus productos. Conclusión: Los beneficios de la Directiva 2004/24/CE para la salud pública española podrían ser menos de los esperados (AU)

The effect of the European traditional use directive on the register of herbal medicinal products in Spain.

BACKGROUND: Directive 2004/24/EC, which came into force in 2011, created new regulatory requirements for traditional herbal medicines (THM). This study compared the Spanish THM registry before and after the Directive came fully into force in 2011. METHODS: We consulted the herbal medicinal plant and drug catalogues (General Council of the Official Colleges of Pharmacists), the website of the European Medicines Agency (EMA), and retail web sites. RESULTS: Of 315 THM (from 39 companies) licensed in Spain in 2010, only 48 (10 companies) remained licensed in 2013, mainly due to their withdrawal: the EMA had received just 123 applications from Spain and at least 34% formerly licensed THM had shifted to the less strictly regulated food sector, while up to 54% might have disappeared from the market. However, there is still a significant presence of retail websites making illegal health claims. CONCLUSION: In Spain, the public health benefits of the Directive 2004/24/EC might be less than expected.

MEDLINE-based assessment of animal studies on Chinese herbal medicine.

UNLABELLED: ETHNO-PHARMACOLOGICAL RELEVANCE: The scientific proof and clinical validation of Chinese herbal medicine (CHM) require a rigorous approach that includes chemical standardization, biological assays, animal studies and clinical trials. AIM OF THE STUDY: To assess the experimental design of animal studies on the activity of CHM by selection and scrutinizing of a series of papers in some major disease areas. MATERIALS AND METHODS: We have analyzed the English publications reported in MEDLINE (ISI web of knowledge). RESULTS: Our data showed that (i) research of CHM during the last 10 years had been highly intensified and become more accessible worldwide through increased publications in English, although still most authors had Chinese names; (ii) English journals publishing animal research of CHM were comparable to those publishing animal studies of non-Chinese phytotherapy in terms of impact factor; and (iii) published data on authentication and quality control of CHM, as well as research design of animal studies were far from sufficient to meet the criteria needed to support their reproducibility and reliability. CONCLUSIONS AND PERSPECTIVES: The recent decade witnessed an increase in CHM research activities and CHM English publications. Based on common problems identified in publications on CHM animal studies, we have proposed a checklist that could help in preliminary selection of publications lacking the most common problems and thus would be useful for a quick search of reproducible CHM regimens that are likely to be effective in a given context. The second application of this checklist is to help avoid the most common problems when designing experiments.

Emergent growth cone responses to combinations of Slit1 and Netrin 1 in thalamocortical axon topography.

How guidance cues are integrated during the formation of complex axonal tracts remains largely unknown. Thalamocortical axons (TCAs), which convey sensory and motor information to the neocortex, have a rostrocaudal topographic organization initially established within the ventral telencephalon [1-3]. Here, we show that this topography is set in a small hub, the corridor, which contains matching rostrocaudal gradients of Slit1 and Netrin 1. Using in vitro and in vivo experiments, we show that Slit1 is a rostral repellent that positions intermediate axons. For rostral axons, although Slit1 is also repulsive and Netrin 1 has no chemotactic activity, the two factors combined generate attraction. These results show that Slit1 has a dual context-dependent role in TCA pathfinding and furthermore reveal that a combination of cues produces an emergent activity that neither of them has alone. Our study thus provides a novel framework to explain how a limited set of guidance cues can generate a vast diversity of axonal responses necessary for proper wiring of the nervous system.

Specificity and plasticity of thalamocortical connections in Sema6A mutant mice.

The establishment of connectivity between specific thalamic nuclei and cortical areas involves a dynamic interplay between the guidance of thalamocortical axons and the elaboration of cortical areas in response to appropriate innervation. We show here that Sema6A mutants provide a unique model to test current ideas on the interactions between subcortical and cortical guidance mechanisms and cortical regionalization. In these mutants, axons from the dorsal lateral geniculate nucleus (dLGN) are misrouted in the ventral telencephalon. This leads to invasion of presumptive visual cortex by somatosensory thalamic axons at embryonic stages. Remarkably, the misrouted dLGN axons are able to find their way to the visual cortex via alternate routes at postnatal stages and reestablish a normal pattern of thalamocortical connectivity. These findings emphasize the importance and specificity of cortical cues in establishing thalamocortical connectivity and the spectacular capacity of the early postnatal cortex for remapping initial sensory representations.