14 research outputs found

    Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

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    [This corrects the article DOI: 10.1186/s13054-016-1208-6.]

    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

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    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

    BMP- and neuropilin 1-mediated motor axon navigation relies on spastin alternative translation.

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    Functional analyses of genes responsible for neurodegenerative disorders have unveiled crucial links between neurodegenerative processes and key developmental signalling pathways. Mutations in SPG4-encoding spastin cause hereditary spastic paraplegia (HSP). Spastin is involved in diverse cellular processes that couple microtubule severing to membrane remodelling. Two main spastin isoforms are synthesised from alternative translational start sites (M1 and M87). However, their specific roles in neuronal development and homeostasis remain largely unknown. To selectively unravel their neuronal function, we blocked spastin synthesis from each initiation codon during zebrafish development and performed rescue analyses. The knockdown of each isoform led to different motor neuron and locomotion defects, which were not rescued by the selective expression of the other isoform. Notably, both morphant neuronal phenotypes were observed in a CRISPR/Cas9 spastin mutant. We next showed that M1 spastin, together with HSP proteins atlastin 1 and NIPA1, drives motor axon targeting by repressing BMP signalling, whereas M87 spastin acts downstream of neuropilin 1 to control motor neuron migration. Our data therefore suggest that defective BMP and neuropilin 1 signalling may contribute to the motor phenotype in a vertebrate model of spastin depletion.See acknowledgements in paper. In addition, the following funder statement has been added to the acknowledgements section of the paper at the proof stage (and is not in the attached manuscript file): ER and RA are supported by grant MR/M00046X/1 from the UK Medical Research Counci

    RM fetal en las anomalías del SNC: Aspectos de interés para el obstetra Abnormalities in fetal CNS: Interesting issues to the obstetrician

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    La resonancia magnética (RM) fetal es una técnica de imagen en auge, útil en la valoración del cerebro y columna fetal. Ayuda a estudiar el desarrollo cerebral fetal y se puede realizar un diagnóstico precoz de las anomalías congénitas. La imagen de RM muestra gran resolución de contraste y permite diferenciar mejor que la ecografía entre hallazgos normales y patológicos. Además, algunas malformaciones cerebrales o lesiones destructivas ocultas en la ecografía prenatal pueden ser detectadas por RM. Revisamos las indicaciones, utilidad, seguridad, aspectos técnicos de la RM fetal y la apariencia del desarrollo cerebral fetal, y evaluamos su contribución en el diagnóstico de las patologías de las diferentes regiones cerebrales y de la patología espinal fetal.<br>Fetal MR imaging (MRI) is an increasingly available technique used to evaluate the fetal brain and spine, because it provides a unique opportunity to evaluate fetal brain development and to make an early diagnosis of congenital abnormalities. MRI allows a better differentiation between normal and abnormal signal intensity of fetal tissues due to its higher contrast resolution compared to prenatal sonography (US). Therefore, structural abnormalities such as brain malformations and destructive lesions that could be sonographically occult on prenatal sonography can be detected at fetal MRI. We review indications, utility, safety, and technical aspects of fetal MR imaging and the appearance of normal fetal brain development evaluating its contribution in the diagnosis of fetal diseases of different brain regions and spinal disorders

    36th International Symposium on Intensive Care and Emergency Medicine : Brussels, Belgium. 15-18 March 2016.

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    Isotope ratios of H, C, and O in CO2 and H2O of the Martian atmosphere

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    Stable isotope ratios of H, C, and O are powerful indicators of a wide variety of planetary geophysical processes, and for Mars they reveal the record of loss of its atmosphere and subsequent interactions with its surface such as carbonate formation. We report in situ measurements of the isotopic ratios of D/H and O-18/O-16 in water and C-13/C-12, O-18/O-16, O-17/O-16, and (CO)-C-13-O-18/(CO)-C-12-O-16 in carbon dioxide, made in the martian atmosphere at Gale Crater from the Curiosity rover using the Sample Analysis at Mars (SAM)'s tunable laser spectrometer (TLS). Comparison between our measurements in the modern atmosphere and those of martian meteorites such as ALH 84001 implies that the martian reservoirs of CO2 and H2O were largely established similar to 4 billion years ago, but that atmospheric loss or surface interaction may be still ongoing

    The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis

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    © 2017 British Journal of Anaesthesia Background: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Methods: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. Results: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32–0.77); P\u3c0.01], but no difference in complication rates [OR 1.02 (0.88–1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62–0.92); P\u3c0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61–0.88); P\u3c0.01; I2=89%). Conclusions: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine
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