Acral Acquired Cutis Laxa Associated with IgA Multiple Myeloma, Joint Hyper laxity and Urticarial Neutrophilic Dermatosis

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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/)

Energy and Antioxidant Responses of Pacific Oyster Exposed to Trace Levels of Pesticides

International audienceHere, we assess the physiological effects induced by environmental concentrations of pesticides in Pacific oyster Crassostrea gigas. Oysters were exposed for 14 d to trace levels of metconazole (0.2 and 2 mu g/L), isoproturon (0.1 and 1 mu g/L), or both in a mixture (0.2 and 0.1 mu g/L, respectively). Exposure to trace levels of pesticides had no effect on the filtration rate, growth, and energy reserves of oysters. However, oysters exposed to metconazole and isoproturon showed an overactivation of the sensing-kinase AMP-activated protein kinase alpha (AMPK alpha), a key enzyme involved in energy metabolism and more particularly glycolysis. In the meantime, these exposed oysters showed a decrease in hexokinase and pyruvate kinase activities, whereas 2-DE proteomic revealed that fructose-1,6-bisphosphatase (F-1,6-BP), a key enzyme of gluconeogenesis, was upregulated. Activities of antioxidant enzymes were higher in oysters exposed to the highest pesticide concentrations. Both pesticides enhanced the superoxide dismutase activity of oysters. Isoproturon enhanced catalase activity, and metconazole enhanced peroxiredoxin activity. Overall, our results show that environmental concentrations of metconazole or isoproturon induced subtle changes in the energy and antioxidant metabolisms of oysters

Proteomic signatures of the oyster metabolic response to herpesvirus OsHV-1 μVar infection

International audiencePacific oyster Crassostrea gigas were inoculated with OsHV-1 at low load (control) or high load (challenged) to better understand the pathogenesis of ostreid herpesvirus 1 (OsHV-1 mu Var) and to determine which metabolic pathways might be affected during infection. Animals were sampled for proteomic analysis two days post-injection, at the same time as OsHV-1 initiated an intense replication phase in challenged oysters. Twenty-five abundant protein spots that showed a marked change in accumulated levels were identified using a two-dimensional electrophoresis (2-DE) proteomic approach. Overall, these proteins are involved in cytoskeleton organization, protein turnover, induction of stress signals, signalling pathways and energy metabolism. Challenged oysters exhibited an increased glycolysis and VDAC accumulation, which reflect a “Warburg effect” as initially reported in cancer cells and more recently in shrimp infected with virus. The results presented here should be useful for identifying potential biomarkers of disease resistance and developing antiviral measures. (C) 2014 Elsevier B.V. All rights reserved

Physiological changes in Pacific oyster Crassostrea gigas exposed to the herpesvirus OsHV-1 μvar

Since 2008, mass mortality events of Crassostrea gigas have been occurring along the French coast when seawater temperature exceeds 16ºC. These mortality events are related to a particular genotype of the ostreid herpesvirus named OsHV-1 μvar. The present study aimed to detail various physiological aspects underlying the onset of the disease. In the laboratory, both exposed (infected) and naïve (healthy) oysters were maintained at 13.0°C and 20.6ºC. These temperatures were respectively lower and higher than the threshold values of 16°C at which the disease generally occur. At 20.6ºC, exposed oysters were characterized by a reduction in energetic reserves (carbohydrates and triglycerides) together with a decrease in protein content. Sterols levels were lower in exposed oysters than in naïve individuals, irrespective of temperature. Finally, activities of some key enzymes related to energetics were similar in exposed and naïve oysters and did not change with temperature. This result suggests that although energetic reserves were being diminished in infected oysters, their metabolic activities remained similar to that of healthy animals

Metabolic responses of clam Ruditapes philippinarum exposed to its pathogen Vibrio tapetis in relation to diet

International audienceWe investigated the effect of brown ring disease (BRD) development and algal diet on energy reserves and activity of enzymes related to energy metabolism, antioxidant system and immunity in Manila clam, Ruditapes philippinarum. We found that algal diet did not impact the metabolic response of clams exposed to Vibrio tapetis. At two days post-injection (dpi), activities of superoxide dismutase and glutathione peroxidase (GPx) decreased whereas activities of nitric oxide synthase (iNOS) and catalase increased in infected clams, although no clinical signs were visible (BRD−). At 7 dpi, activities of several antioxidant and immune-related enzymes were markedly increased in BRD-likely indicating an efficient reactive oxygen species (ROS) scavenging compared to animals which developed clinical signs of BRD (BRD+). Therefore, resistance to BRD clinical signs appearance was associated with higher detoxification of ROS and enhancement of immune response. This study provides new biochemical indicators of disease resistance and a more comprehensive view of the global antioxidant response of clam to BRD development

Temperature modulate disease susceptibility of the Pacific oyster Crassostrea gigas and virulence of the Ostreid herpesvirus type 1

Temperature triggers marine diseases by changing host susceptibility and pathogen virulence. Oyster mortalities associated with the Ostreid herpesvirus type 1 (OsHV-1) have occurred seasonally in Europe when the seawater temperature range reaches 16–24 °C. Here we assess how temperature modulates oyster susceptibility to OsHV-1 and pathogen virulence. Oysters were injected with OsHV-1 suspension incubated at 21 °C, 26 °C and 29 °C and were placed in cohabitation with healthy oysters (recipients) at these three temperatures according to a fractional factorial design. Survival was followed for 14 d and recipients were sampled for OsHV-1 DNA quantification and viral gene expression. The oysters were all subsequently placed at 21 °C to evaluate the potential for virus reactivation, before being transferred to oyster farms to evaluate their long-term susceptibility to the disease. Survival of recipients at 29 °C (86%) was higher than at 21 °C (52%) and 26 °C (43%). High temperature (29 °C) decreased the susceptibility of oysters to OsHV-1 without altering virus infectivity and virulence. At 26 °C, the virulence of OsHV-1 was enhanced. Differences in survival persisted when the recipients were all placed at 21 °C, suggesting that OsHV-1 did not reactivate. Additional oyster mortality followed the field transfer, but the overall survival of oysters infected at 29 °C remained higher

The Voltage-Dependent Anion Channel (VDAC) of Pacific Oysters Crassostrea gigas Is Upaccumulated During Infection by the Ostreid Herpesvirus-1 (OsHV-1): an Indicator of the Warburg Effect

WOS:000424459500008International audienceVoltage-dependent anion channel (VDAC) is a key mitochondrial protein. VDAC drives cellular energy metabolism by controlling the influx and efflux of metabolites and ions through the mitochondrial membrane, playing a role in its permeabilization. This protein exerts a pivotal role during the white spot syndrome virus (WSSV) infection in shrimp, through its involvement in a particular metabolism that plays in favor of the virus, the Warburg effect. The Warburg effect corresponds to an atypical metabolic shift toward an aerobic glycolysis that provides energy for rapid cell division and resistance to apoptosis. In the Pacific oyster Crassostrea gigas, the Warburg effect occurs during infection by Ostreid herpesvirus (OsHV-1). At present, the role of VDAC in the Warburg effect, OsHV-1 infection and apoptosis is unknown. Here, we developed a specific antibody directed against C. gigas VDAC. This tool allowed us to quantify the tissue-specific expression of VDAC, to detect VDAC oligomers, and to follow the amount of VDAC in oysters deployed in the field. We showed that oysters sensitive to a mortality event in the field presented an accumulation of VDAC. Finally, we propose to use VDAC quantification as a tool to measure the oyster susceptibility to OsHV-1 depending on its environment

Exosomes as a novel way of interneuronal communication.

International audienceExosomes are small extracellular vesicles which stem from endosomes fusing with the plasma membrane; they contain lipids, proteins and RNAs that are able to modify receiving cells. Functioning of the brain relies on synapses, and certain patterns of synaptic activity can change the strength of responses at sparse groups of synapses, to modulate circuits underlying associations and memory. These local changes of the synaptic physiology in one neuron driven by another have, so far, been explained by classical signal transduction modulating transcription, translation and post-translational modifications. We have accumulated in vitro evidence that exosomes released by neurons in a way depending on synaptic activity can be recaptured by other neurons. Some lipids, proteins and RNAs contained in exosomes secreted by emitting neurons could directly modify signal transduction and protein expression in receiving cells. Exosomes may be an ideal mechanism for anterograde and retrograde information transfer across synapses underlying local changes in synaptic plasticity. Exosomes might also participate in the spreading across the nervous system of pathological proteins such as PrPSc (abnormal disease-specific conformation of prion protein), APP (amyloid precursor protein) fragments, phosphorylated tau or α-synuclein

Connecting organic to mineral: How the physiological state of an ecosystem-engineer is linked to its habitat structure

WOS:000464891100006International audienceThe honeycomb worm Sabellaria alveolata is capable of building extensive bioconstructions, including what are currently considered Europe's largest biogenic reefs. The size and volume of these bioconstructions, however, vary greatly, such that not all habitats engineered by S. alveolata may be easily identified as reefs. Given that European environmental legislation protects marine habitats that are classified as "reefs", it is important to identity a clear set of definition criteria. Furthermore, quantifiable and unequivocal criteria are also needed to evaluate the ecological (health) state of these reefs, in order to best monitor and protect them. Here we propose new terminology to describe the physical appearance of these bioconstructions and attempt to link these physical criteria to the physiological state of the tube-building polychaete. We tested whether a bioconstruction displaying outward signs of growth is built by "healthy" worms devoid of physiological stress by analysing three macromolecules (carbohydrates, proteins, lipids), four polar lipid fatty acids, six neutral lipid fatty acid markers and three metabolic enzymes (citrate synthase, catalase and superoxide dismutase). The worms were sampled in bioconstructions of different "Type" (veneer vs. hummock), "Phase" (progradation vs. retrogradation), and "Shore Level" (high shore vs. low shore) at Champeaux in Mont-Saint-Michel Bay, France. Our results show that worms sampled in retrograding reefs (i.e. displaying signs of erosion and colonisation by epibionts such as oysters or mussels), were less physiologically stressed than worms sampled in prograding bioconstructions, possibly due to lower intraspecific competition and hence greater food availability. We therefore suggest management measures should encompass the whole mosaic of biogenic construction Types and Phases. We propose the inclusion of the polar lipid fatty acid arachidonic acid, in combination with the activity of two metabolic enzymes, citrate synthase and superoxide dismutase, as the three key biochemical markers to consider for quantitative information on the physiological state of this particular ecosystem engineer. Our results also revealed the influence of both sex and size on fatty acid and enzyme levels, highlighting the importance of taking into account both these variables when sampling and subsequently pooling individuals by sex and size category for laboratory analyses. Once seasonal and site variation have been addressed, these biochemical indicators could be examined in parallel with S. alveolata bioconstruction physical criteria as part of a European-wide protocol for monitoring ecological status in this potential reef habitat