Osteocondritis disecante de astrágalo : a propósito de un caso clínico tratado mediante técnica mínimamente invasiva

Osteochondritis dissecans of the talus in adults is quite common; on the contrary, the juvenile forms are unusual and are usually associated with sportive activities. It is a subject not very studied yet, because the majority of the treatment guides and studies are based on adult cases. The treatment in juvenile forms is still controversial. A conservative treatment of the osteochondritis dissecans of the talus is usually indicated in I and II stage lesions of the Berndt and Harty classification. In these stages, good results have been observed in knee and elbow, nevertheless, in the talus, the studies have shown big percentage of failure. The aim of a surgical treatment of this type of lesions with intact cartilage is the vascularization of the damaged zone using vascular channels formation by drilling. However, dorsomedial lesions of the talus are frequently inaccessible to anterior arthroscopic drilling without damaging the intact cartilage. This is why retrograde drilling techniques have been developed. A clinical case of a child presenting osteocondritis dissecans of the talus, in medial location is presented. A conservative treatment was at first attempted and due to the failure of the above mentioned treatment, a surgical approach by retrograde drilling was performed with an arthroscopic technique

Identification, introgression, and validation of fruit volatile QTLs from a red-fruited wild tomato species

[EN] Volatile organic compounds (VOCs) are major determinants of fruit flavor, a primary objective in tomato breeding. A recombinant inbred line (RIL) population consisting of 169 lines derived from a cross between Solanum lycopersicum and a red-fruited wild tomato species Solanum pimpinellifolium accession (SP) was characterized for VOCs in three different seasons. Correlation and hierarchical cluster analyses were performed on the 52 VOCs identified, providing a tool for the putative assignation of individual compounds to metabolic pathways. Quantitative trait locus (QTL) analysis, based on a genetic linkage map comprising 297 single nucleotide polymorphisms (SNPs), revealed 102 QTLs (75% not described previously) corresponding to 39 different VOCs. The SP alleles exerted a positive effect on most of the underlying apocarotenoid volatile QTLs-regarded as desirable for liking tomato-indicating that alleles inherited from SP are a valuable resource for flavor breeding. An introgression line (IL) population developed from the same parental genotypes provided 12 ILs carrying a single SP introgression and covering 85 VOC QTLs, which were characterized at three locations. The results showed that almost half of the QTLs previously identified in the RILs maintained their effect in an IL form, reinforcing the value of these QTLs for flavor/aroma breeding in cultivated tomato.We thank Erika Moro for valuable help in volatile analysis of the ILs. WB was supported by a fellowship granted by the Universidad de Costa Rica and CSIC-Spain by way of a collaboration agreement between CSIC/UCR. Volatile profiling was performed in the Metabolomic facilities of the IBMCP, CSIC (Spain). This work was supported in part by the Spanish MINECO Project AGL2015-65246-R co-financed by EU FEDER, MINECO Project AGL2011-26957, and the Bilateral agreements of Scientific and Technological Cooperation between the Spanish National Research Council (CSIC) and the Italian National Research Council (CNR). Funding for this project was provided through TRADITOM. TRADITOM has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 634561. Networking activities were supported by COST action Fruit Quality FA 1106.Rambla Nebot, JL.; Medina, A.; Fernández Del Carmen, MA.; Barrantes, W.; Grandillo, S.; Cammareri, M.; López Casado, G.... (2016). Identification, introgression, and validation of fruit volatile QTLs from a red-fruited wild tomato species. Journal of Experimental Botany. 68(3):429-442. https://doi.org/10.1093/jxb/erw455S429442683Alba, J. M., Montserrat, M., & Fernández-Muñoz, R. (2008). 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Development of a set of near isogenic and backcross recombinant inbred lines containing most of the Lycopersicon hirsutum genome in a L. esculentum genetic background: A tool for gene mapping and gene discovery. Genome, 43(5), 803-813. doi:10.1139/gen-43-5-803Orzaez, D., Medina, A., Torre, S., Fernández-Moreno, J. P., Rambla, J. L., Fernández-del-Carmen, A., … Granell, A. (2009). A Visual Reporter System for Virus-Induced Gene Silencing in Tomato Fruit Based on Anthocyanin Accumulation. Plant Physiology, 150(3), 1122-1134. doi:10.1104/pp.109.139006Rambla, J. L., Alfaro, C., Medina, A., Zarzo, M., Primo, J., & Granell, A. (2015). Tomato fruit volatile profiles are highly dependent on sample processing and capturing methods. Metabolomics, 11(6), 1708-1720. doi:10.1007/s11306-015-0824-5Rambla, J. L., Tikunov, Y. M., Monforte, A. J., Bovy, A. G., & Granell, A. (2013). The expanded tomato fruit volatile landscape. 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B., Taylor, M. G., Schmelz, E., Huffaker, A., … Klee, H. J. (2014). A 13-lipoxygenase, TomloxC, is essential for synthesis of C5 flavour volatiles in tomato. Journal of Experimental Botany, 65(2), 419-428. doi:10.1093/jxb/ert382Sim, S.-C., Durstewitz, G., Plieske, J., Wieseke, R., Ganal, M. W., Van Deynze, A., … Francis, D. M. (2012). Development of a Large SNP Genotyping Array and Generation of High-Density Genetic Maps in Tomato. PLoS ONE, 7(7), e40563. doi:10.1371/journal.pone.0040563Simkin, A. J., Schwartz, S. H., Auldridge, M., Taylor, M. G., & Klee, H. J. (2004). The tomato carotenoid cleavage dioxygenase 1 genes contribute to the formation of the flavor volatiles β-ionone, pseudoionone, and geranylacetone. The Plant Journal, 40(6), 882-892. doi:10.1111/j.1365-313x.2004.02263.xSkouroumounis GK Massywestropp RA Sefton MA Williams PJ . 1993. beta-Damascenone formation in juices and wines. In: Schreier P Winterhalter P , eds. 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Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

A first update on mapping the human genetic architecture of COVID-19

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