Nueva técnica de sutura artroscópica transósea del manguito de los rotadores: estudio anatómico

Se ha realizado un estudio anatómico experimental sobre cadáver que ha fundamentado el desarrollo de una técnica alternativa de reparación artroscópica del manguito rotador, puramente transósea. Se han utilizado 10 hombros de cadáver fresco congelado. Mediante una guía externa diseñada específicamente para esta técnica, se han efectuado perforaciones en el troquíter con diferentes angulaciones. En cada uno de los ángulos se ha medido la distancia al nervio axilar, así como el grosor de la pastilla ósea de troquíter obtenida. El análisis de los datos ha mostrado una distribución normal de los valores, y diferencias estadísticamente significativas entre los resultados obtenidos en cada ángulo de colocación de la guía externa (p<0.001). Conclusiones: La sutura artroscópica transósea del manguito rotador, realizada mediante una guía externa a través del deltoides, es una técnica factible, que puede llevarse a cabo con márgenes de seguridad respecto a una hipotética lesión del nervio axilar.An anatomical study with ten fresh shoulder specimens was carried out in order to establish the safest angle to perform a new arthroscopic technnique for true transosseous rotator cuff repair. With an external guide designed for this study, several osseous tunnels were made through the greater tuberosity using different angles. The minimum distance from the drill to the axillary nerve was measured with each angle, as well as the thickness of the osseous bridge in the greater tuberosity. Statistically significant differences were observed between the measurements obtained with each angle of the external guide (p<0.001). From our data it is concluded that transosseous arthroscopic repair of the rotator cuff with an external guide is a feasible technique and can be performed with minimal risk for the axillary nerve

Transcriptome sequencing for SNP discovery across Cucumis melo

Background: Melon (Cucumis melo L.) is a highly diverse species that is cultivated worldwide. Recent advances in massively parallel sequencing have begun to allow the study of nucleotide diversity in this species. The Sanger method combined with medium-throughput 454 technology were used in a previous study to analyze the genetic diversity of germplasm representing 3 botanical varieties, yielding a collection of about 40,000 SNPs distributed in 14,000 unigenes. However, the usefulness of this resource is limited as the sequenced genotypes do not represent the whole diversity of the species, which is divided into two subspecies with many botanical varieties variable in plant, flowering, and fruit traits, as well as in stress response. As a first step to extensively document levels and patterns of nucleotide variability across the species, we used the high-throughput SOLiD¿ system to resequence the transcriptomes of a set of 67 genotypes that had previously been selected from a core collection representing the extant variation of the entire species.Results: The deep transcriptome resequencing of all of the genotypes, grouped into 8 pools (wild African agrestis, Asian agrestis and acidulus, exotic Far Eastern conomon, Indian momordica and Asian dudaim and flexuosus, commercial cantalupensis, subsp. melo Asian and European landraces, Spanish inodorus landraces, and Piel de Sapo breeding lines) yielded about 300 M reads. Short reads were mapped to the recently generated draft genome assembly of the DHL line Piel de Sapo (inodorus) x Songwhan Charmi (conomon) and to a new version of melon transcriptome. Regions with at least 6X coverage were used in SNV calling, generating a melon collection with 303,883 variants. These SNVs were dispersed across the entire C. melo genome, and distributed in 15,064 annotated genes. The number and variability of in silico SNVs differed considerably between pools. Our finding of higher genomic diversity in wild and exotic agrestis melons from India and Africa as compared to commercial cultivars, cultigens and landraces from Eastern Europe, Western Asia and the Mediterranean basin is consistent with the evolutionary history proposed for the species. Group-specific SNVs that will be useful in introgression programs were also detected. In a sample of 143 selected putative SNPs, we verified 93% of the polymorphisms in a panel of 78 genotypes.Conclusions: This study provides the first comprehensive resequencing data for wild, exotic, and cultivated (landraces and commercial) melon transcriptomes, yielding the largest melon SNP collection available to date and representing a notable sample of the species diversity. This data provides a valuable resource for creating a catalog of allelic variants of melon genes and it will aid in future in-depth studies of population genetics, marker-assisted breeding, and gene identification aimed at developing improved varieties. © 2012 Blanca et al.; licensee BioMed Central Ltd.This project was carried out in the frame of the MELONOMICS project (2009-2012) of the Fundacion Genoma Espana.Blanca Postigo, JM.; Esteras Gómez, C.; Ziarsolo Areitioaurtena, P.; Perez, D.; Fernández-Pedrosa, V.; Collado, C.; Rodríguez De Pablos, R.... (2012). Transcriptome sequencing for SNP discovery across Cucumis melo. BMC Genomics. 13(280):1-18. doi:10.1186/1471-2164-13-280S1181328

Characterization of ApoJ-reconstituted high-density lipoprotein (rHDL) nanodisc for the potential treatment of cerebral β-amyloidosis

Altres ajuts: Fundació La Marató de TV3 [40/U/2014]Cerebral β-amyloidosis is a major feature of Alzheimer's disease (AD), characterized by the accumulation of β-amyloid protein (Aβ) in the brain. Several studies have implicated lipid/lipoprotein metabolism in the regulation of β-amyloidosis. In this regard, HDL (High Density Lipoprotein)-based therapies could ameliorate pathological features associated with AD. As apolipoprotein J (ApoJ) is a natural chaperone that interacts with Aβ, avoiding its aggregation and toxicity, in this study we propose to prepare reconstituted rHDL-rApoJ nanoparticles by assembling phospholipids with recombinant human ApoJ (rApoJ). Hence, rHDL particles were prepared using the cholate dialysis method and characterized by N-PAGE, dynamic light scattering, circular dichroism and electron transmission microscopy. The preparation of rHDL particles showed two-sized populations with discoidal shape. Functionally, rHDL-rApoJ maintained the ability to prevent the Aβ fibrillization and mediated a higher cholesterol efflux from cultured macrophages. Fluorescently-labelled rHDL-rApoJ nanoparticles were intravenously administrated in mice and their distribution over time was determined using an IVIS Xenogen® imager. It was confirmed that rHDL-rApoJ accumulated in the cranial region, especially in old transgenic mice presenting a high cerebral Aβ load. In conclusion, we have standardized a reproducible protocol to produce rHDL-rApoJ nanoparticles, which may be potentially considered as a therapeutic option for β-amyloid-related pathologies

Peripheral administration of human recombinant ApoJ/clusterin modulates brain beta-amyloid levels in APP23 mice

Altres ajuts: Fundació La Marató de TV3 [40/U/2014]Background: ApoJ/clusterin is a multifunctional protein highly expressed in the brain. The implication of ApoJ in β-amyloid (Aβ) fibrillization and clearance in the context of Alzheimer's disease has been widely studied, although the source and concentration of ApoJ that promotes or inhibits Aβ cerebral accumulation is not clear yet. ApoJ is abundant in plasma and approximately 20% can appear bound to HDL-particles. In this regard, the impact of plasmatic ApoJ and its lipidation status on cerebral β-amyloidosis is still not known. Hence, our main objective was to study the effect of a peripheral increase of free ApoJ or reconstituted HDL particles containing ApoJ in an experimental model of cerebral β-amyloidosis. Methods: Fourteen-month-old APP23 transgenic mice were subjected to subchronic intravenous treatment with rHDL-rApoJ nanodiscs or free rApoJ for 1 month. Aβ concentration and distribution in the brain, as well as Aβ levels in plasma and CSF, were determined after treatments. Other features associated to AD pathology, such as neuronal loss and neuroinflammation, were also evaluated. Results: Both ApoJ-based treatments prevented the Aβ accumulation in cerebral arteries and induced a decrease in total brain insoluble Aβ levels. The peripheral treatment with rApoJ also induced an increase in the Aβ levels in CSF, whereas the concentration remained unaltered in plasma. At all the endpoints studied, the lipidation of rApoJ did not enhance the protective properties of free rApoJ. The effects obtained after subchronic treatment with free rApoJ were accompanied by a reduction in hippocampal neuronal loss and an enhancement of the expression of a phagocytic marker in microglial cells surrounding Aβ deposits. Finally, despite the activation of this phagocytic phenotype, treatments did not induce a global neuroinflammatory status. In fact, free rApoJ treatment was able to reduce the levels of interleukin-17 (IL17) and keratinocyte chemoattractant (KC) chemokine in the brain. Conclusions: Our results demonstrate that an increase in circulating human rApoJ induces a reduction of insoluble Aβ and CAA load in the brain of APP23 mice. Thus, our study suggests that peripheral interventions, based on treatments with multifunctional physiological chaperones, offer therapeutic opportunities to regulate the cerebral Aβ load

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.</p

Modelo espacialmente explícito de estimación de las temperaturas extremas diarias en la Ciudad de Santiago, Chile, usando imágenes MODIS e información meteorológica

Ponencia presentada en: XI Congreso de la Asociación Española de Climatología celebrado en Cartagena entre el 17 y el 19 de octubre de 2018.[ES]En estudios relacionados para el monitoreo de la isla térmica en una ciudad es necesario el estimar la variabilidad espacial de la temperatura del aire. Este problema es muy importante cuando la densidad de estaciones meteorológicas presentes es de baja densidad, lo cual limita obtener campos térmicos confiables. El presente trabajo presenta un método para estimar las temperaturas extremas diarias a partir de datos de temperatura superficial diurna y nocturna obtenidos por el sensor MODIS (LST) a nivel de la Ciudad de Santiago de Chile. El método aplicado se basa en el uso de regresiones lineales espacialmente explícitas o regresiones ponderadas geográficamente (GWR), donde se estima la inestabilidad paramétrica a nivel de toda el área de estudio, donde las variables independientes usadas corresponden a la altitud y el índice de vegetación de diferencia normalizada (NDVI). Las regresiones fueron todas significativas, sin embargo, los mejores resultados del ajuste y evaluación de los modelos lineales para temperaturas máximas y mínimas se obtienen con datos de LST-MODIS día y noche en forma conjunta (mixtos) que por separado. Los resultados muestran que las regresiones espacialmente explícitas GWR presentan una buena precisión para la estimación de las temperaturas extremas diarias a partir de la temperatura superficial de noche y de día MODIS en comparación con OLS.[EN]In related studies for monitoring the thermal island in a city it is necessary to estimate the spatial variability of air temperature. This problem is very important when the density of meteorological stations present a low density, which limits to obtain reliable thermal fields. The present work shows a method to estimate the daily extreme temperatures from daytime and night surface temperature data obtained by the MODIS sensor (LST) at the level of the City of Santiago de Chile. The applied method is based on the use of spatially explicit linear regressions or geographically weighted regressions (GWR), where parametric instability is estimated at the level of the entire study area, where the independent variables used correspond to the altitude and the vegetation index of normalized difference (NDVI). The regressions were all significant, however, the best results of the adjustment and evaluation of the linear models for maximum and minimum air temperatures are obtained with day and night LST-MODIS data jointly than separately. The results show that the spatially explicit GWR regressions present good accuracy for the estimation of daily extreme temperatures from the MODIS day and night surface temperature compared to OLS.Esta investigación fue financiada por la Comisión Nacional de Investigación Científica y Tecnológica (CONICYT), por medio del proyecto FONDECYT 1161809

Spatio-Temporal Variation of the Urban Heat Island in Santiago, Chile during Summers 2005-2017

Urban heat islands (UHIs) can present significant risks to human health. Santiago, Chile has around 7 million residents, concentrated in an average density of 480 people/km(2). During the last few summer seasons, the highest extreme maximum temperatures in over 100 years have been recorded. Given the projections in temperature increase for this metropolitan region over the next 50 years, the Santiago UHI could have an important impact on the health and stress of the general population. We studied the presence and spatial variability of UHIs in Santiago during the summer seasons from 2005 to 2017 using Moderate Resolution Imaging Spectroradiometer (MODIS) satellite imagery and data from nine meteorological stations. Simple regression models, geographic weighted regression (GWR) models and geostatistical interpolations were used to find nocturnal thermal differences in UHIs of up to 9 degrees C, as well as increases in the magnitude and extension of the daytime heat island from summer 2014 to 2017. Understanding the behavior of the UHI of Santiago, Chile, is important for urban planners and local decision makers. Additionally, understanding the spatial pattern of the UHI could improve knowledge about how urban areas experience and could mitigate climate change.Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 1161809 Publication Development Fund initiative of the Universidad Mayo

Characterization of ApoJ-reconstituted high-density lipoprotein (rHDL) nanodisc for the potential treatment of cerebral β-amyloidosis

Abstract Cerebral β-amyloidosis is a major feature of Alzheimer’s disease (AD), characterized by the accumulation of β-amyloid protein (Aβ) in the brain. Several studies have implicated lipid/lipoprotein metabolism in the regulation of β-amyloidosis. In this regard, HDL (High Density Lipoprotein)-based therapies could ameliorate pathological features associated with AD. As apolipoprotein J (ApoJ) is a natural chaperone that interacts with Aβ, avoiding its aggregation and toxicity, in this study we propose to prepare reconstituted rHDL-rApoJ nanoparticles by assembling phospholipids with recombinant human ApoJ (rApoJ). Hence, rHDL particles were prepared using the cholate dialysis method and characterized by N-PAGE, dynamic light scattering, circular dichroism and electron transmission microscopy. The preparation of rHDL particles showed two-sized populations with discoidal shape. Functionally, rHDL-rApoJ maintained the ability to prevent the Aβ fibrillization and mediated a higher cholesterol efflux from cultured macrophages. Fluorescently-labelled rHDL-rApoJ nanoparticles were intravenously administrated in mice and their distribution over time was determined using an IVIS Xenogen® imager. It was confirmed that rHDL-rApoJ accumulated in the cranial region, especially in old transgenic mice presenting a high cerebral Aβ load. In conclusion, we have standardized a reproducible protocol to produce rHDL-rApoJ nanoparticles, which may be potentially considered as a therapeutic option for β-amyloid-related pathologies