Investigating insecticides in water and sediment of the Choapa River, Chile: do they sink or swim?

In Chile, freshwater rivers travel short distances from the Andes Mountains to the Pacific Ocean. The areas immediately adjacent to the rivers are used to produce fruits and vegetables, and it is possible that these areas can contribute insecticides and herbicides to the riverine systems during rainstorm runoff events. The paucity of knowledge about the occurrence and environmental fate of pesticides in these novel systems presents a unique challenge for ecotoxicology. In the Choapa River, we have found that a native pencil catfish, the (Trichomycterus areolatus) exhibits alterations in gene expression. The alterations are occurring in genes that are biomarkers for endocrine function as well as oxidative stress. Given the biological evidence, we sought to determine 1) whether pesticides detected in the Choapa River were consistent with the changes observed in the fish biomarkers, and 2) whether these agrichemicals were predominately found in surface waters or sediment. To address this objective, we collected water and sediment samples from 5 different sites along the Choapa River, then analyzed for a suite of 27 common herbicides, insecticides and their metabolites. Water and sediment samples were prepared onsite then analyzed at the Water Science Lab, University of Nebraska Lincoln, using gas chromatography–mass spectrometry (GC-MS). Preliminary analysis detected the herbicides propazine and metribuzin, as well as the insecticide carbofuran, all of which varied seasonally and spatially within the Choapa River. Finding from our chemical analysis and observations of seasonal and El Nino trends reveal a complex interplay between agrichemical occurrence and river discharge in the Choapa Basin. Additionally, the results of this study illustrate the challenges of analytical environmental chemistry in unique environments, and the importance of appropriate sample schemes of water and sediment

Cynomolgus macaques naturally infected with Trypanosoma cruzi-I exhibit an overall mixed pro-inflammatory/modulated cytokine signature characteristic of human Chagas disease

Background: Non-human primates have been shown to be useful models for Chagas disease. We previously reported that natural T. cruzi infection of cynomolgus macaques triggers clinical features and immunophenotypic changes of peripheral blood leukocytes resembling those observed in human Chagas disease. In the present study, we further characterize the cytokine-mediated microenvironment to provide supportive evidence of the utility of cynomolgus macaques as a model for drug development for human Chagas disease. Methods and findings: In this cross-sectional study design, flow cytometry and systems biology approaches were used to characterize the ex vivo and in vitro T. cruzi-specific functional cytokine signature of circulating leukocytes from TcI-T. cruzi naturally infected cynomolgus macaques (CH). Results showed that CH presented an overall CD4+-derived IFN-γ pattern regulated by IL-10-derived from CD4+ T-cells and B-cells, contrasting with the baseline profile observed in non-infected hosts (NI). Homologous TcI-T. cruzi-antigen recall in vitro induced a broad pro-inflammatory cytokine response in CH, mediated by TNF from innate/adaptive cells, counterbalanced by monocyte/B-cell-derived IL-10. TcIV-antigen triggered a more selective cytokine signature mediated by NK and T-cell-derived IFN-γ with modest regulation by IL-10 from T-cells. While NI presented a cytokine network comprised of small number of neighborhood connections, CH displayed a complex cross-talk amongst network elements. Noteworthy, was the ability of TcI-antigen to drive a complex global pro-inflammatory network mediated by TNF and IFN-γ from NK-cells, CD4+ and CD8+ T-cells, regulated by IL-10+CD8+ T-cells, in contrast to the TcIV-antigens that trigger a modest network, with moderate connecting edges. Conclusions: Altogether, our findings demonstrated that CH present a pro-inflammatory/regulatory cytokine signature similar to that observed in human Chagas disease. These data bring additional insights that further validate these non-human primates as experimental models for Chagas disease

De novo Assembly and Analysis of the Chilean Pencil Catfish Trichomycterus areolatus Transcriptome

Trichomycterus areolatus is an endemic species of pencil catfish that inhabits the riffles and rapids of many freshwater ecosystems of Chile. Despite its unique adaptation to Chile’s high gradient watersheds and therefore potential application in the investigation of ecosystem integrity and environmental contamination, relatively little is known regarding the molecular biology of this environmental sentinel. Here, we detail the assembly of the Trichomycterus areolatus transcriptome, a molecular resource for the study of this organism and its molecular response to the environment. RNA-Seq reads were obtained by next-generation sequencing with an Illumina® platform and processed using PRINSEQ. The transcriptome assembly was performed using TRINITY assembler. Transcriptome validation was performed by functional characterization with KOG, KEGG, and GO analyses. Additionally, differential expression analysis highlights sex-specific expression patterns, and a list of endocrine and oxidative stress related transcripts are included

Reconstructing an Ancestral Mammalian Immune Supercomplex from a Marsupial Major Histocompatibility Complex

The first sequenced marsupial genome promises to reveal unparalleled insights into mammalian evolution. We have used theMonodelphis domestica (gray short-tailed opossum) sequence to construct the first map of a marsupial major histocompatibility complex (MHC). The MHC is the most gene-dense region of the mammalian genome and is critical to immunity and reproductive success. The marsupial MHC bridges the phylogenetic gap between the complex MHC of eutherian mammals and the minimal essential MHC of birds. Here we show that the opossum MHC is gene dense and complex, as in humans, but shares more organizational features with non-mammals. The Class I genes have amplified within the Class II region, resulting in a unique Class I/II region. We present a model of the organization of the MHC in ancestral mammals and its elaboration during mammalian evolution. The opossum genome, together with other extant genomes, reveals the existence of an ancestral “immune supercomplex” that contained genes of both types of natural killer receptors together with antigen processing genes and MHC genes

Determinants of the access to remote specialised services provided by national sarcoma reference centres

BACKGROUND: Spatial inequalities in cancer management have been evidenced by studies reporting lower quality of care or/and lower survival for patients living in remote or socially deprived areas. NETSARC+ is a national reference network implemented to improve the outcome of sarcoma patients in France since 2010, providing remote access to specialized diagnosis and Multidisciplinary Tumour Board (MTB). The IGéAS research program aims to assess the potential of this innovative organization, with remote management of cancers including rare tumours, to go through geographical barriers usually impeding the optimal management of cancer patients. METHODS: Using the nationwide NETSARC+ databases, the individual, clinical and geographical determinants of the access to sarcoma-specialized diagnosis and MTB were analysed. The IGéAS cohort (n = 20,590) includes all patients living in France with first sarcoma diagnosis between 2011 and 2014. Early access was defined as specialised review performed before 30 days of sampling and as first sarcoma MTB discussion performed before the first surgery. RESULTS: Some clinical populations are at highest risk of initial management without access to sarcoma specialized services, such as patients with non-GIST visceral sarcoma for diagnosis [OR 1.96, 95% CI 1.78 to 2.15] and MTB discussion [OR 3.56, 95% CI 3.16 to 4.01]. Social deprivation of the municipality is not associated with early access on NETSARC+ remote services. The quintile of patients furthest away from reference centres have lower chances of early access to specialized diagnosis [OR 1.18, 95% CI 1.06 to 1.31] and MTB discussion [OR 1.24, 95% CI 1.10 to 1.40] but this influence of the distance is slight in comparison with clinical factors and previous studies on the access to cancer-specialized facilities. CONCLUSIONS: In the context of national organization driven by reference network, distance to reference centres slightly alters the early access to sarcoma specialized services and social deprivation has no impact on it. The reference networks' organization, designed to improve the access to specialized services and the quality of cancer management, can be considered as an interesting device to reduce social and spatial inequalities in cancer management. The potential of this organization must be confirmed by further studies, including survival analysis

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Listeria pathogenesis and molecular virulence determinants

The gram-positive bacterium Listeria monocytogenes is the causative agent of listeriosis, a highly fatal opportunistic foodborne infection. Pregnant women, neonates, the elderly, and debilitated or immunocompromised patients in general are predominantly affected, although the disease can also develop in normal individuals. Clinical manifestations of invasive listeriosis are usually severe and include abortion, sepsis, and meningoencephalitis. Listeriosis can also manifest as a febrile gastroenteritis syndrome. In addition to humans, L. monocytogenes affects many vertebrate species, including birds. Listeria ivanovii, a second pathogenic species of the genus, is specific for ruminants. Our current view of the pathophysiology of listeriosis derives largely from studies with the mouse infection model. Pathogenic listeriae enter the host primarily through the intestine. The liver is thought to be their first target organ after intestinal translocation. In the liver, listeriae actively multiply until the infection is controlled by a cell-mediated immune response. This initial, subclinical step of listeriosis is thought to be common due to the frequent presence of pathogenic L. monocytogenes in food. In normal indivuals, the continual exposure to listerial antigens probably contributes to the maintenance of anti-Listeria memory T cells. However, in debilitated and immunocompromised patients, the unrestricted proliferation of listeriae in the liver may result in prolonged low-level bacteremia, leading to invasion of the preferred secondary target organs (the brain and the gravid uterus) and to overt clinical disease. L. monocytogenes and L. ivanovii are facultative intracellular parasites able to survive in macrophages and to invade a variety of normally nonphagocytic cells, such as epithelial cells, hepatocytes, and endothelial cells. In all these cell types, pathogenic listeriae go through an intracellular life cycle involving early escape from the phagocytic vacuole, rapid intracytoplasmic multiplication, bacterially induced actin-based motility, and direct spread to neighboring cells, in which they reinitiate the cycle. In this way, listeriae disseminate in host tissues sheltered from the humoral arm of the immune system. Over the last 15 years, a number of virulence factors involved in key steps of this intracellular life cycle have been identified. This review describes in detail the molecular determinants of Listeria virulence and their mechanism of action and summarizes the current knowledge on the pathophysiology of listeriosis and the cell biology and host cell responses to Listeria infection. This article provides an updated perspective of the development of our understanding of Listeria pathogenesis from the first molecular genetic analyses of virulence mechanisms reported in 1985 until the start of the genomic era of Listeria research

Le système Navitrack® permet-il de mieux atteindre l'objectif de longueur et de latéralisation du membre inférieur lors d'une prothèse totale de hanche ?

L'inégalité de longueur des membres inférieurs après PTH est une complication à l'origine de douleurs, d'impotence fonctionnelle et de litiges. Une augmentation de l'offset de plus de 5 millimètres péjore les résultats fonctionnels. Or, les méthodes de planification et de mesure peropératoires manquent de précision. Il s'agissait d'une étude prospective comparant 50 PTH naviguées et 50 PTH non naviguées en deux séries continues. La technique opératoire utilisait le système Navitrack®, système passif de chirurgie assistée par ordinateur sans imagerie complémentaire. Nous n'avons pas retrouvé de différence significative entre les deux séries pour l'objectif de longueur ou pour la restitution de l'offset global. Le nombre limité des effectifs, qui pouvait méconnaitre une différence significative, et l'analyse radiographique, qui comporte des approximations, représentaient des limites de cette étude. D'autres systèmes de navigation des PTH permettent d'améliorer la position des implants mais posent le problème de la fiabilité du plan pelvien antérieur et du rallongement de la durée opératoire. Malgré le caractère séduisant de ce type de système simplifié qui ne s'intéresse qu'à la longueur et à l'offset global, nos résultats ne nous permettent pas pour le moment de recommander l'utilisation systématique de cette technologie.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

L'utilisation de l'hypnose éricksonienne chez les adolescents

Cette thèse tente d expliquer certaines facettes de l hypnose éricksonienne et comment cette dernière peut être utilisée avec les adolescents dans le cadre de la thérapie. La première partie de ce texte développe plusieurs concepts propres à l'hypnose éricksonienne. Il y est exposé plusieurs définitions et théories permettant de mieux percevoir l hypnose éricksonienne. Certaines clés historiques et plusieurs éléments pratiques y sont également présentés. La deuxième partie transpose ces concepts dans le domaine de la pédospychiatrie en général. On y retrouve plusieurs propositions d abord de l hypnose en fonction de l âge du patient. Enfin, il est proposé d adapter les différentes possibilités de l hypnose éricksonienne au contexte de l adolescence à travers plusieurs cas cliniques.This thesis tries to explain every facets of the ericksonian hypnosis and how the latter can be used with the teenagers within the framework of the therapy. The first part of this text develops several concepts suitable for ericksonian hypnosis. It is exposed there several definitions and theories making it possible to better perceive ericksonian hypnosis. Some historical dates and several practical elements are also presented there. The second part transposes these concepts in the field of the pédospychiatry. It is found several proposals to approach hypnosis according to the age of the patient. Finally it is proposed to adapt the various possibilities of ericksonian hypnosis to the context of adolescence through several clinical cases.ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF