High throughput estimation of functional cell activities reveals disease mechanisms and predicts relevant clinical outcomes

This work is supported by grants BIO2014- 57291-R from the Spanish Ministry of Economy and Competitiveness and “Plataforma de Recursos Biomoleculares y Bioinformáticos” PT13/0001/0007 from the ISCIII, both co-funded with European Regional Development Funds (ERDF); PROMETEOII/2014/025 from the Generalitat Valenciana (GVA-FEDER); Fundació la Marató TV3 (ref. 20133134); and EU H2020- INFRADEV-1-2015-1 ELIXIR-EXCELERATE (ref. 676559) and EU FP7-People ITN Marie Curie Project (ref 316861)

Factors associated with the development of septic shock in patients with candidemia: A post hoc analysis from two prospective cohorts

Background: Almost one third of the patients with candidemia develop septic shock. The understanding why some patients do and others do not develop septic shock is very limited. The objective of this study was to identify variables associated with septic shock development in a large population of patients with candidemia. Methods: A post hoc analysis was performed on two prospective, multicenter cohort of patients with candidemia from 12 hospitals in Spain and Italy. All episodes occurring from September 2016 to February 2018 were analyzed to assess variables associated with septic shock development defined according to The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3). Results: Of 317 candidemic patients, 99 (31.2%) presented septic shock attributable to candidemia. Multivariate logistic regression analysis identifies the following factors associated with septic shock development: age > 50 years (OR 2.57, 95% CI 1.03-6.41, p = 0.04), abdominal source of the infection (OR 2.18, 95% CI 1.04-4.55, p = 0.04), and admission to a general ward at the time of candidemia onset (OR 0.21, 95% CI, 0.12-0.44, p = 0.001). Septic shock development was independently associated with a greater risk of 30-day mortality (OR 2.14, 95% CI 1.08-4.24, p = 0.02). Conclusions: Age and abdominal source of the infection are the most important factors significantly associated with the development of septic shock in patients with candidemia. Our findings suggest that host factors and source of the infection may be more important for development of septic shock than intrinsic virulence factors of organisms

Evaluation of natural and tracer fluorescent emission methods for droplet size measurements in a diesel spray

The final publication is available at Springer via http://dx.doi.org/10.1007/s12239-012-0070-zSpray sizing that records fluorescent emission and scattered light has been widely applied to spray diagnostics over the last two decades. Different experimental strategies have been developed, but comparing the different solutions offered has remained of interest to experimentalists. In this work, a comparison of two fluorescence strategies for measuring droplet size in the liquid phase of a last-generation DI diesel spray is conducted. The natural fluorescent emission of a commercial diesel fuel and the fluorescence emitted by a tracer (Rhodamine B) are compared using theoretical and experimental approaches. The LIF/Mie ratio commonly called Planar Droplet Sizing (PDS) technique is applied in two different ways to elucidate the possible advantages of using a fluorescent dopant. The sprays were injected under non-evaporative conditions into a constant pressure vessel that simulates densities present at the moment of injection in currently used passenger car diesel engines. Characterization of the signal properties was performed by measuring the absorption coefficient, fluorescence emission spectrum, quantum yield and lifetime of both configurations. The scattered light and fluorescence intensities were calculated to verify the dependencies of the droplet surface and volume. When applying the two techniques to quantify droplet size in dense diesel sprays, the results show that signal weakness and lack of control over the properties of natural fluorescence produce distortion in the shape of the spray and cause measurements to be unreliable. © 2012 The Korean Society of Automotive Engineers and Springer-Verlag Berlin Heidelberg.This research has been funded in the frame of the project PROFUEL reference TRA2011-26293 from Ministerio de Ciencia e Innovacion. The injectors are part of the ECN international project.Pastor Soriano, JV.; Payri, R.; Salavert Fernandez, J.; Manin, J. (2012). Evaluation of natural and tracer fluorescent emission methods for droplet size measurements in a diesel spray. International Journal of Automotive Technology. 13(5):713-724. https://doi.org/10.1007/s12239-012-0070-zS713724135Albrecht, H. E., Damaschke, N., Borys, M. and Tropea, C. (2003). Laser Doppler and Phase Doppler Measurement Techniques. Springer. Berlin.Barnes, M. D., Whitten, W. B. and Ramsey, J. M. (1994). Enhanced fluorescence yields through cavity quantumelectrodynamic effects in microdroplets. J. Optical Society of America B 11,7, 1297–1304.Benajes, J., Molina, S., Novella, R., Amorim, R., Ben Hadj Hamouda, H. and Hardy, J. (2010). Comparison of two injection systems in an HSDI diesel engine using split injection and different injector nozzles. Int. J. Automotive Technology 11,2, 139–146.Charalampous, G. and Hardalupas, Y. (2011). 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Revisiting and modelling the woodland farming system of the early Neolithic Linear Pottery Culture (LBK), 5600–4900 B.C

International audienceThis article presents the conception and the conceptual results of a modelling representation of the farming systems of the Linearbandkeramik Culture (LBK). Assuming that there were permanent fields (PF) then, we suggest four ways that support the sustainability of such a farming system over time: a generalized pollarding and coppicing of trees to increase the productivity of woodland areas for foddering more livestock, which itself can then provide more manure for the fields, a generalized use of pulses grown together with cereals during the same cropping season, thereby reducing the needs for manure. Along with assumptions limiting bias on village and family organizations, the conceptual model which we propose for human environment in the LBK aims to be sustainable for long periods and can thereby overcome doubts about the PFs hypothesis for the LBK farming system. Thanks to a reconstruction of the climate of western Europe and the consequent vegetation pattern and productivity arising from it, we propose a protocol of experiments and validation procedures for both testing the PFs hypothesis and defining its eco-geographical area

Streptococcus intermedius causing infective endocarditis and abscesses: a report of three cases and review of the literature

<p>Abstract</p> <p>Background</p> <p><it>Streptococcus intermedius </it>is a member of the Streptococcus anginosus group. Clinical disease with <it>S. intermedius </it>is characterized by abscess formation and rarely endocarditis. Identification of <it>Streptococcus intermedius </it>is difficult, leading to the development of molecular methods to more accurately identify and characterize this organism.</p> <p>Case presentation</p> <p>Over a period of 6 months we encountered three cases of invasive <it>Streptococcus intermedius </it>infection presenting as hepatic abscesses, brain abscess, and endocarditis. We confirmed our microbiologic diagnosis through 16S sequencing and found a common virulence gene in each case.</p> <p>Conclusion</p> <p>Our report illustrates three different clinical manifestations due to <it>Streptococcus intermedius </it>infection that can be encountered in healthy individuals in a community hospital setting. To our knowledge, this is the first case of <it>Streptococcus intermedius </it>endocarditis confirmed by 16S sequencing analysis. The use of molecular methods may allow a better understanding of the epidemiology and pathogenesis of this organism.</p

The place of millet in food globalization during Late Prehistory as evidenced by new bioarchaeological data from the Caucasus

Two millets, Panicum miliaceum and Setaria italica, were domesticated in northern China, around 6000 BC. Although its oldest evidence is in Asia, possible independent domestication of these species in the Caucasus has often been proposed. To verify this hypothesis, a multiproxy research program (Orimil) was designed to detect the first evidence of millet in this region. It included a critical review of the occurrence of archaeological millet in the Caucasus, up to Antiquity; isotopic analyses of human and animal bones and charred grains; and radiocarbon dating of millet grains from archaeological contexts dated from the Early Bronze Age (3500–2500 BC) to the 1st Century BC. The results show that these two cereals were cultivated during the Middle Bronze Age (MBA), around 2000–1800 BC, especially Setaria italica which is the most ancient millet found in Georgia. Isotopic analyses also show a significant enrichment in 13C in human and animal tissues, indicating an increasing C4 plants consumption at the same period. More broadly, our results assert that millet was not present in the Caucasus in the Neolithic period. Its arrival in the region, based on existing data in Eurasia, was from the south, without excluding a possible local domestication of Setaria italica

Differential metabolic activity and discovery of therapeutic targets using summarized metabolic pathway models

Abstract In spite of the increasing availability of genomic and transcriptomic data, there is still a gap between the detection of perturbations in gene expression and the understanding of their contribution to the molecular mechanisms that ultimately account for the phenotype studied. Alterations in the metabolism are behind the initiation and progression of many diseases, including cancer. The wealth of available knowledge on metabolic processes can therefore be used to derive mechanistic models that link gene expression perturbations to changes in metabolic activity that provide relevant clues on molecular mechanisms of disease and drug modes of action (MoA). In particular, pathway modules, which recapitulate the main aspects of metabolism, are especially suitable for this type of modeling. We present Metabolizer, a web-based application that offers an intuitive, easy-to-use interactive interface to analyze differences in pathway metabolic module activities that can also be used for class prediction and in silico prediction of knock-out (KO) effects. Moreover, Metabolizer can automatically predict the optimal KO intervention for restoring a diseased phenotype. We provide different types of validations of some of the predictions made by Metabolizer. Metabolizer is a web tool that allows understanding molecular mechanisms of disease or the MoA of drugs within the context of the metabolism by using gene expression measurements. In addition, this tool automatically suggests potential therapeutic targets for individualized therapeutic interventions

Virtual Ontogeny of Cortical Growth Preceding Mental Illness

Background: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. Methods: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. Results: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. Conclusions: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy

Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019

Altres ajuts: Spanish AIDS Research Network; European Funding for Regional Development (FEDER).Objectives: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. Methods: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. Results: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). Conclusions: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population

Barriers to health care services for migrants living with HIV in Spain

BACKGROUND: In Spain, migrants are disproportionately affected by HIV and experience high rates of late diagnosis. We investigated barriers to health care access among migrants living with HIV (MLWH) in Spain. METHODS: Cross sectional electronic survey of 765 adult HIV-positive migrants recruited within 18 health care settings between July 2013 and July 2015. We collected epidemiological, demographic, behavioral and clinical data. We estimated the prevalence and risk factors of self-reported barriers to health care using multivariable logistic regression. RESULTS: Of those surveyed, 672 (88%) had information on health care access barriers: 23% were women, 63% from Latin America and Caribbean, 14% from Sub-Saharan Africa and 15% had an irregular immigration status. Men were more likely to report barriers than women (24% vs. 14%, P = 0.009). The main barriers were: lengthy waiting times for an appointment (9%) or in the clinic (7%) and lack of a health card (7%). Having an irregular immigration status was a risk factor for experiencing barriers for both men (OR: (4.0 [95%CI: 2.2–7.2]) and women (OR: 10.5 [95%CI: 3.1–34.8]). Men who experienced racial stigma (OR: 3.1 [95%CI: 1.9–5.1]) or food insecurity (OR: 2.1 [95%CI: 1.2–3.4]) were more likely to report barriers. Women who delayed treatment due to medication costs (6.3 [95%CI: 1.3–30.8]) or had a university degree (OR: 5.8 [95%CI: 1.3–25.1]) were more likely to report barriers. CONCLUSION: Health care barriers were present in one in five5 MLWH, were more common in men and were associated to legal entitlement to access care, perceived stigma and financial constraints