The impact of polyphenols on chondrocyte growth and survival: a preliminary report

Background: Imbalances in the functional binding of fibroblast growth factors (FGFs) to their receptors (FGFRs) have consequences for cell proliferation and differentiation that in chondrocytes may lead to degraded cartilage. The toxic, proinflammatory, and oxidative response of cytokines and FGFs can be mitigated by dietary polyphenols. Objective: We explored the possible effects of polyphenols in the management of osteoarticular diseases using a model based on the transduction of a mutated human FGFR3 (G380R) in murine chondrocytes. This mutation is present in most cases of skeletal dysplasia and is responsible for the overexpression of FGFR3 that, in the presence of its ligand, FGF9, results in toxic effects leading to altered cellular growth. Design: Different combinations of dietary polyphenols derived from plant extracts were assayed in FGFR3 (G380R) mutated murine chondrocytes, exploring cell survival, chloride efflux, extracellular matrix (ECM) generation, and grade of activation of mitogen-activated protein kinases. Results: Bioactive compounds from Hibiscus sabdariffa reversed the toxic effects of FGF9 and restored normal growth, suggesting a probable translation to clinical requests in humans. Indeed, these compounds activated the intracellular chloride efflux, increased ECM generation, and stimulated cell proliferation. The inhibition of mitogen-activated protein kinase phosphorylation was interpreted as the main mechanism governing these beneficial effects. Conclusions: These findings support the rationale behind the encouragement of the development of drugs that repress the overexpression of FGFRs and suggest the dietary incorporation of supplementary nutrients in the management of degraded cartilage.The authors are grateful for the constant support provided by the Hospital Universitari de Sant Joan and the Universitat Rovira i Virgili. Salvador Fernández-Arroyo is the recipient of a Sara Borrell grant (CD12/00672) from the Instituto de Salud Carlos III, Madrid, Spain. The authors also thank the Andalusian Regional Government Council of Innovation and Science for the Excellence Project P11-CTS-7625 and Generalitat Valenciana for the project PROMETEO/2012/007. This work was also supported by projects of the Fundación Areces and the Fundación MAGAR

What to consider when pseudohypoparathyroidism is ruled out: IPPSD and differential diagnosis

Background: Pseudohypoparathyroidism (PHP) is a rare disease whose phenotypic features are rather difficult to identify in some cases. Thus, although these patients may present with the Albright''s hereditary osteodystrophy (AHO) phenotype, which is characterized by small stature, obesity with a rounded face, subcutaneous ossifications, mental retardation and brachydactyly, its manifestations are somewhat variable. Indeed, some of them present with a complete phenotype, whereas others show only subtle manifestations. In addition, the features of the AHO phenotype are not specific to it and a similar phenotype is also commonly observed in other syndromes. Brachydactyly type E (BDE) is the most specific and objective feature of the AHO phenotype, and several genes have been associated with syndromic BDE in the past few years. Moreover, these syndromes have a skeletal and endocrinological phenotype that overlaps with AHO/PHP. In light of the above, we have developed an algorithm to aid in genetic testing of patients with clinical features of AHO but with no causative molecular defect at the GNAS locus. Starting with the feature of brachydactyly, this algorithm allows the differential diagnosis to be broadened and, with the addition of other clinical features, can guide genetic testing. Methods: We reviewed our series of patients (n = 23) with a clinical diagnosis of AHO and with brachydactyly type E or similar pattern, who were negative for GNAS anomalies, and classify them according to the diagnosis algorithm to finally propose and analyse the most probable gene(s) in each case. Results: A review of the clinical data for our series of patients, and subsequent analysis of the candidate gene(s), allowed detection of the underlying molecular defect in 12 out of 23 patients: five patients harboured a mutation in PRKAR1A, one in PDE4D, four in TRPS1 and two in PTHLH. Conclusions: This study confirmed that the screening of other genes implicated in syndromes with BDE and AHO or a similar phenotype is very helpful for establishing a correct genetic diagnosis for those patients who have been misdiagnosed with "AHO-like phenotype" with an unknown genetic cause, and also for better describing the characteristic and differential features of these less common syndromes

Ciencias Sociales: Economía y Humanidades

Este volumen I contiene 29 capítulos arbitrados que se ocupan de estos asuntos en Tópicos Selectos de Ciencias Sociales: Economía y Humanidades, elegidos de entre las contribuciones, reunimos algunos investigadores y estudiantes.Gómez, presenta un breve examen de la producción y comercialización de rosa en México; Arpi y Portillo realiza un estudio en México sobre el ingreso mínimo de las familias que identifica la línea de pobreza alimentaria en el área rural del sur de México, 2012; Bravo realiza un pequeño estudio donde hablará sobre el análisis comparado del Sector Gubernamental y la Economía Mexicana desde la perspectiva de los eslabonamientos productivos Hirshman-Rasmuss; Caamal, Pat, Jerónimo y Romero realizan un estudio sobre los canales de comercialización de limón persa en el municipio de Martínez de la Torre, Veracruz; Macías y Perales nos hablarán sobre una análisis del comercio estratégico en el TLCAN: El Estado en la política agrícola de biocombustibles; Figueroa, Pérez y Godínez se expresan acerca de la importancia de la comercialización del café en México; Sepúlveda, Sepúlveda y Pérez realizan un diagnóstico, retos del comercio electrónico en el Sector Agroindustrial Mexicano; Duana mediante su trabajo nos muestra y habla sobre la inversión extranjera directa y su impacto en crecimiento de México, un análisis en prospectiva: 1999-2010; Figueroa, Pérez y Ramírez hacen un estudio acerca sobre la importancia de la Banca en México; Pérez, Figueroa, Godínez y Pérez presenta un trabajo acerca de la competitividad de la producción agrícola en México, un análisis regional; Rodríguez, Espinosa y Márquez analizan todo acerca de el SIAL productor de quesos en Poxtla, competividad y territorio; Garza nos habla acerca de la intermediación financiera al servicio de la comunidad indígena: el fondo regional indígena Tarhiata Keri; Arroyo, Aguilar, Santoyo y Muñoz realizan un estudio acerca de la demanda de Importaciones de durazno (Prunus pérsica L. Batsch) en México procedentes de Estados Unidos de América (1982-2011); Loera y Sepúlveda analizan los parámetros de la productividad forestal en la producción de madera en rollo; Pérez, Morett y Tecpan realizan un análisis de factores sociales, ambientales y económicos del territorio rural cercano a la ciudad de México; Godínez, Figueroa y Pérez realizan un estudio acerca de la crisis económica mundial y su efecto sobre los flujos migratorios de América Latina; Magadán, Hernández y Escalona presentan la tipología de los sujetos sociales que intervienen en el mercado campesino de Ocotlán Oaxaca; Tavera y Cobos nos hablan de la normalización del proceso de compostaje: una opción para desarrollar el mercado de la composta; Piña y Pérez hablan acerca de la reestructuración del capitalismo y crisis política en México; Gonzáles, Rucoba y Ramírez realizan un estudio de la rentabilidad de la producción de miel en el municipio de León, Guanjuato; Ramírez, Gutiérrez y Figueroa realizan un estudio acerca de la economía del maíz en la región metropolitana, Chiapas, 2014; Bueno, Méndez y Cruz realizan un estudio y análisis de los centros de educación y cultura ambiental, necesidad de profesionalización Pedagógica de facilitadores ambientales; Pat, Caamal, Jerónimo y Mendoza presentan un estudio acerca de los Costos y competitividad de la producción del limón persa en el municipio de Martínez de la Torre, Veracruz. Vizuet presenta un trabajo de la construcción polisémica e histórica del concepto de la pobreza; Navarrete, Ríos y Arévalo presentan un estudio acerca de la producción ejidal de tomate rojo (Lycopersicum esculentum) en el DR-017, y su huella hídrica; Pérez y Piña hablan acerca de la productividad e inversión extranjera: La industria de Alimentos; Pérez, Figueroa, Godínez y Gómez presentan el trabajo sobre el sector primario en México; Pérez, Figueroa, Godínez y Gómez presentan acerca de los subsidios al campo como instrumento de política económica en México; Venegas, Perales y Del Valle realizan un estudio de rentabilidad de biodigestores y motogeneradores para diferentes tamaños de granjas porcinas en Michoacán

NEOTROPICAL XENARTHRANS: a data set of occurrence of xenarthran species in the Neotropics

Xenarthrans – anteaters, sloths, and armadillos – have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with 24 domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, ten anteaters, and six sloths. Our dataset includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data-paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the south of the USA, Mexico, and Caribbean countries at the northern portion of the Neotropics, to its austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records (n=5,941), and Cyclopes sp. has the fewest (n=240). The armadillo species with the most data is Dasypus novemcinctus (n=11,588), and the least recorded for Calyptophractus retusus (n=33). With regards to sloth species, Bradypus variegatus has the most records (n=962), and Bradypus pygmaeus has the fewest (n=12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other datasets of Neotropical Series which will become available very soon (i.e. Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans dataset

Ciencias Sociales: Economía y Humanidades HANDBOOK T-I

Se presenta un breve examen de la producción y comercialización de rosa en México; un estudio en México sobre el ingreso mínimo de las familias que identifica la línea de pobreza alimentaria en el área rural del sur de México, 2012; un pequeño estudio donde hablará sobre el análisis comparado del Sector Gubernamental y la Economía Mexicana desde la perspectiva de los eslabonamientos productivos Hirshman-Rasmuss; un estudio sobre los canales de comercialización de limón persa en el municipio de Martínez de la Torre, Veracruz; una análisis del comercio estratégico en el TLCAN: El Estado en la política agrícola de biocombustibles; también se expresan acerca de la importancia de la comercialización del café en México; un diagnóstico, retos del comercio electrónico en el Sector Agroindustrial Mexicano; trabajo nos muestra y habla sobre la inversión extranjera directa y su impacto en crecimiento de México, un análisis en prospectiva: 1999-2010; un estudio acerca sobre la importancia de la Banca en México; un trabajo acerca de la competitividad de la producción agrícola en México, un análisis regional; se analizan todo acerca de el SIAL productor de quesos en Poxtla, competividad y territorio; se habla acerca de la intermediación financiera al servicio de la comunidad indígena: el fondo regional indígena Tarhiata Keri; ademas un estudio acerca de la demanda de Importaciones de durazno (Prunus pérsica L. Batsch) en México procedentes de Estados Unidos de América (1982-2011); Loera y Sepúlveda analizan los parámetros de la productividad forestal en la producción de madera en rollo; un análisis de factores sociales, ambientales y económicos del territorio rural cercano a la ciudad de México; un estudio acerca de la crisis económica mundial y su efecto sobre los flujos migratorios de América Latina; Magadán, Hernández y Escalona presentan la tipología de los sujetos sociales que intervienen en el mercado campesino de Ocotlán Oaxaca; la normalización del proceso de compostaje: una opción para desarrollar el mercado de la composta; acerca de la reestructuración del capitalismo y crisis política en México; la rentabilidad de la producción de miel en el municipio de León, Guanjuato; la economía del maíz en la región metropolitana, Chiapas, 2014; análisis de los centros de educación y cultura ambiental, necesidad de profesionalización Pedagógica de facilitadores ambientales; los Costos y competitividad de la producción del limón persa en el municipio de Martínez de la Torre, Veracruz

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified