37 research outputs found

    ES cells-derived ectomesenchymal cells for tooth engineering.

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    Recent progresses in stem cell biology and tissue engineering allow considering the possible development of new therapies for compensating the dental tissue losses associated with traumas, pathologies or ageing. The possibility of generating a tooth by mimicking development through reassociations between dental epithelial cells and ectomesenchymal cells derived from the neural crest (NC) has been demonstrated in the mouse. In the search of cell sources to be used for a human transfer, pluripotent stem cells could represent a good alternative. Our study thus focuses on obtaining, ectomesenchymal cells from pluripotent ES cells, capable of promoting tooth histomorphogenesis, when reassociated with a competent dental epithelium. To this end, two ES differentiation protocols, using cyclopamine or a combination of FGF2 and BMP4, have been developed and tested for their capacity to generate such cells. The differentiated ES cells were characterized by quantitative RT-PCR. Both protocols led the cells to acquire in 10 days a mesenchymal-like cell morphology. Rapidly after induction, the cells loose their expression of pluripotent genes while sequentially activating typical NC specifiers. However, the kinetics of gene activation differed between the 2 protocols. Interestingly, Twist, a gene whose expression in the NC is associated with a commitment towards an ectomesenchymal fate, is only activated under the influence of FGF2 and BMP4. Reassociation experiments with a competent epithelium will allow testing the odontogenic potential of the differentiated ES cells. These experiments performed in the mouse system should allow defining a strategy for obtaining odontogenic competent human cells. Les progrès en matière de biologie de cellules souches et d’ingénierie tissulaire permettent d’envisager le développement de nouvelles thérapies pour pallier les pertes de tissus dentaires consécutives à des traumatismes, des situations pathologiques ou au vieillissement. La possibilité de générer une dent en mimant le développement, par réassociations entre cellules dentaires épithéliales et mésenchymateuses dérivées des crêtes neurales (CN), a été démontrée chez la souris. Dans la recherche de ressources cellulaires utilisables pour un transfert chez l’homme, les cellules souches pluripotentes pourraient constituer une alternative. Notre but est d’obtenir à partir de ces dernières, des cellules ectomésenchymateuses capables d’interagir avec un épithélium dentaire pour promouvoir l’histomorphogenèse d’une dent. Pour cela, deux protocoles de différenciation de cellules ES, utilisant la cyclopamine ou une combinaison de FGF2/BMP4, ont été mis au point. Les cellules induites ont été caractérisées par PCR quantitative. Les deux protocoles de différenciation amènent les cellules à acquérir en 10 jours, une morphologie de type mésenchymateux. Après induction, l’expression des gènes de pluripotence chute de façon drastique alors que celle des gènes spécificateurs de CN est activée. Toutefois, la cinétique varie selon le protocole. Le gène Twist, dont l’expression dans les CN est associée à un engagement vers l’ectomésenchyme, n’est activé significativement que sous l’action de FGF2/BMP4. Des expériences de réassociations avec un épithélium dentaire sont en cours pour évaluer le potentiel odontogène des cellules ES différenciées. A terme, ces approches menées chez la souris devraient permettre de définir une stratégie pour l’obtention de cellules compétentes humaines.Recent progresses in stem cell biology and tissue engineering allow considering the possible development of new therapies for compensating the dental tissue losses associated with traumas, pathologies or ageing. The possibility of generating a tooth by mimicking development through reassociations between dental epithelial cells and ectomesenchymal cells derived from the neural crest (NC) has been demonstrated in the mouse. In the search of cell sources to be used for a human transfer, pluripotent stem cells could represent a good alternative. Our study thus focuses on obtaining, ectomesenchymal cells from pluripotent ES cells, capable of promoting tooth histomorphogenesis, when reassociated with a competent dental epithelium. To this end, two ES differentiation protocols, using cyclopamine or a combination of FGF2 and BMP4, have been developed and tested for their capacity to generate such cells. The differentiated ES cells were characterized by quantitative RT-PCR. Both protocols led the cells to acquire in 10 days a mesenchymal-like cell morphology. Rapidly after induction, the cells loose their expression of pluripotent genes while sequentially activating typical NC specifiers. However, the kinetics of gene activation differed between the 2 protocols. Interestingly, Twist, a gene whose expression in the NC is associated with a commitment towards an ectomesenchymal fate, is only activated under the influence of FGF2 and BMP4. Reassociation experiments with a competent epithelium will allow testing the odontogenic potential of the differentiated ES cells. These experiments performed in the mouse system should allow defining a strategy for obtaining odontogenic competent human cells. Les progrès en matière de biologie de cellules souches et d’ingénierie tissulaire permettent d’envisager le développement de nouvelles thérapies pour pallier les pertes de tissus dentaires consécutives à des traumatismes, des situations pathologiques ou au vieillissement. La possibilité de générer une dent en mimant le développement, par réassociations entre cellules dentaires épithéliales et mésenchymateuses dérivées des crêtes neurales (CN), a été démontrée chez la souris. Dans la recherche de ressources cellulaires utilisables pour un transfert chez l’homme, les cellules souches pluripotentes pourraient constituer une alternative. Notre but est d’obtenir à partir de ces dernières, des cellules ectomésenchymateuses capables d’interagir avec un épithélium dentaire pour promouvoir l’histomorphogenèse d’une dent. Pour cela, deux protocoles de différenciation de cellules ES, utilisant la cyclopamine ou une combinaison de FGF2/BMP4, ont été mis au point. Les cellules induites ont été caractérisées par PCR quantitative. Les deux protocoles de différenciation amènent les cellules à acquérir en 10 jours, une morphologie de type mésenchymateux. Après induction, l’expression des gènes de pluripotence chute de façon drastique alors que celle des gènes spécificateurs de CN est activée. Toutefois, la cinétique varie selon le protocole. Le gène Twist, dont l’expression dans les CN est associée à un engagement vers l’ectomésenchyme, n’est activé significativement que sous l’action de FGF2/BMP4. Des expériences de réassociations avec un épithélium dentaire sont en cours pour évaluer le potentiel odontogène des cellules ES différenciées. A terme, ces approches menées chez la souris devraient permettre de définir une stratégie pour l’obtention de cellules compétentes humaines

    Disentangling signatures of selection before and after European colonization in latin Americans

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    Throughout human evolutionary history, large-scale migrations have led to intermixing (i.e., admixture) between previously separated human groups. Although classical and recent work have shown that studying admixture can yield novel historical insights, the extent to which this process contributed to adaptation remains underexplored. Here, we introduce a novel statistical model, specific to admixed populations, that identifies loci under selection while determining whether the selection likely occurred post-admixture or prior to admixture in one of the ancestral source populations. Through extensive simulations, we show that this method is able to detect selection, even in recently formed admixed populations, and to accurately differentiate between selection occurring in the ancestral or admixed population. We apply this method to genome-wide SNP data of ∼4,000 individuals in five admixed Latin American cohorts from Brazil, Chile, Colombia, Mexico, and Peru. Our approach replicates previous reports of selection in the human leukocyte antigen region that are consistent with selection post-admixture. We also report novel signals of selection in genomic regions spanning 47 genes, reinforcing many of these signals with an alternative, commonly used local-ancestry-inference approach. These signals include several genes involved in immunity, which may reflect responses to endemic pathogens of the Americas and to the challenge of infectious disease brought by European contact. In addition, some of the strongest signals inferred to be under selection in the Native American ancestral groups of modern Latin Americans overlap with genes implicated in energy metabolism phenotypes, plausibly reflecting adaptations to novel dietary sources available in the Americas

    A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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    Copper, zinc, mercury and arsenic content in Micropogonias furnieri and Mugil platanus of the Montevideo coastal zone, Río de la Plata

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    Abstract Metals (Cu, Zn, Hg) and metalloid (As) concentrations were measured in Micropogonias furnieri and Mugil platanus caught in three areas along the Montevideo coastal zone during winter 2010, spring 2010 and 2011. Compared to previous studies conducted in the zone, both species showed higher (for Cu), similar (for Zn) or lower (for Hg) concentrations. The highest Hg values were found in the M. furnieri of Montevideo bay. There was no spatial variation in Cu, Zn, and As concentrations in muscle, likely due to the high mobility of both species. However, the Cu content in the liver of M. furnieri was higher in fish from the West zone. Cu, Zn and As found in the liver of M. platanus were much higher than in that of M. furnieri. A functional relationship between muscle levels of Zn and Hg and fish length of M. furnieri indicates bioaccumulation of these metals. According to the results, M. furnieri may be used as a temporal bioindicator for Hg, but not as a spatial bioindicator. Mercury levels were below the maximum safety level based on international standard values for human consumption

    Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

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    Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

    A global analysis of terrestrial plant litter dynamics in non-perennial waterways

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    Perennial rivers and streams make a disproportionate contribution to global carbon (C) cycling. However, the contribution of intermittent rivers and ephemeral streams (IRES), which sometimes cease to flow and can dry completely, is largely ignored although they represent over half the global river network. Substantial amounts of terrestrial plant litter (TPL) accumulate in dry riverbeds and, upon rewetting, this material can undergo rapid microbial processing. We present the results of a global research collaboration that collected and analysed TPL from 212 dry riverbeds across major environmental gradients and climate zones. We assessed litter decomposability by quantifying the litter carbon-to-nitrogen ratio and oxygen (O2) consumption in standardized assays and estimated the potential short-term CO2 emissions during rewetting events. Aridity, cover of riparian vegetation, channel width and dry-phase duration explained most variability in the quantity and decomposability of plant litter in IRES. Our estimates indicate that a single pulse of CO2 emission upon litter rewetting contributes up to 10% of the daily CO2 emission from perennial rivers and stream, particularly in temperate climates. This indicates that the contributions of IRES should be included in global C-cycling assessments

    Actividad sexual en adolescencia temprana: problema de salud pública en una ciudad colombiana

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    Antecedentes: El inicio de Ia actividad sexual en adolescentes, está asociada a pobre planificación familiar (PF), mayor tasa de fecundidad y riesgo de adquisición de enfermedades de transmisión sexual (ETS). Objetivo: Evaluar el impacto sobre la fecundidad, planificación familiar y lesiones de cuello uterino en una población de adolescentes y jóvenes, que iniciaron actividad sexual en la adolescencia. Método: Estudio de cohorte retrospectiva. Incluyó 845 adolescentes y jóvenes que iniciaron actividad sexual en la adolescencia y que consultaron a una Institución Prestadora de Servicios de Salud en Tuluá, Colombia. El análisis incluyó estadísticas descriptivas, análisis de riesgo relativo (RR) y atribuible a la exposición (RAexp) expresado en porcentaje, como indicadores de asociación. Resultados: Hubo 203 adolescentes y 642 jóvenes. El promedio de edad de inicio de la actividad sexual fue 16 años (±1,6 años). El 49% no realizaba PF, 34,7% tenía &#8805;1 hijo y 6,9% alguna lesión en cuello uterino. Hubo asociación entre actividad sexual en la adolescencia temprana y tener un hijo, al compararlo con el inicio de la actividad sexual en la adolescencia media (RR: 1,6; IC 95%: 1,2-2,1. RAexp0/35,7%; IC 95%: 13,3-52,4%) y tardía (RR: 2; IC 95%: 1,5-2,6. RAexp0/49%; IC 95%: 31,7-62%). Conclusiones: Nuestros resultados confirman el inicio precoz de la actividad sexual en adolescentes, el bajo uso de anticonceptivos y el riesgo de lesiones cervicales. Programas educativos conducentes al retraso del inicio de la actividad sexual, el uso de métodos anticonceptivos efectivos y de barrera, permitirán reducir las cifras encontradas en este estudio

    Prevalencia de lesiones de bajo y alto grado de cuello uterino en una ciudad colombiana

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    Objetivo: Determinar la prevalencia de las lesiones de bajo y alto grado de cuello uterino en una Institución Prestadora de Servicios de Salud de Tuluá, Colombia, entre los años 2008-2010. Métodos: Se realizó un estudio descriptivo retrospectivo en el que se incluyeron mujeres entre los 15 y 75 años, residentes en el Municipio de Tuluá. Se evaluo la normalidad de las variables cuantitativas, empleándose la mediana o el promedio con sus varianzas según su distribución, y frecuencias y proporciones para las variables categóricas. Resultados: Se incluyeron 3.539 mujeres. La mediana de la edad fue 38 años con rango intercuartil (RI: 29-46 años), la mediana del número de partos 1 (RI: 0-3). En relación a la seguridad social y uso de métodos anticonceptivos, la mayoría eran particulares y no utilizaban ningún método. El 87,5% de las citologías se reportaron como negativas, 8,2% lesión de bajo grado (LSIL), 2,6% células escamosas atípicas de significado indeterminado (ASC-US), 0,9% lesiones de alto grado (HSIL), 0,4% células escamosas atípicas de significado indeterminado de alto grado ASC-H, 0,4% células glandulares atípicas de significado incierto (ASGUS) y 0,2% carcinoma invasor. Conclusión: La prevalencia de las anormalidades citológicas fue baja en todos los grupos analizados, sin embargo, existe un mayor número de LSIL hacia la cuarta década de la vida y en aquellas que iniciaron su vida sexual después de los 40 años. De igual manera se encontró una relación inversa entre el número de partos, planificación familiar hormonal y aparición de lesiones pre neoplásicas
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