HDL Proteome in Hemodialysis Patients: A Quantitative Nanoflow Liquid Chromatography-Tandem Mass Spectrometry Approach

Aside from a decrease in the high-density lipoprotein (HDL) cholesterol levels, qualitative abnormalities of HDL can contribute to an increase in cardiovascular (CV) risk in end-stage renal disease (ESRD) patients undergoing chronic hemodialysis (HD). Dysfunctional HDL leads to an alteration of reverse cholesterol transport and the antioxidant and anti-inflammatory properties of HDL. In this study, a quantitative proteomics approach, based on iTRAQ labeling and nanoflow liquid chromatography mass spectrometry analysis, was used to generate detailed data on HDL-associated proteins. The HDL composition was compared between seven chronic HD patients and a pool of seven healthy controls. To confirm the proteomics results, specific biochemical assays were then performed in triplicate in the 14 samples as well as 46 sex-matched independent chronic HD patients and healthy volunteers. Of the 122 proteins identified in the HDL fraction, 40 were differentially expressed between the healthy volunteers and the HD patients. These proteins are involved in many HDL functions, including lipid metabolism, the acute inflammatory response, complement activation, the regulation of lipoprotein oxidation, and metal cation homeostasis. Among the identified proteins, apolipoprotein C-II and apolipoprotein C-III were significantly increased in the HDL fraction of HD patients whereas serotransferrin was decreased. In this study, we identified new markers of potential relevance to the pathways linked to HDL dysfunction in HD. Proteomic analysis of the HDL fraction provides an efficient method to identify new and uncharacterized candidate biomarkers of CV risk in HD patients

J Clin Immunol

We report a longitudinal analysis of the immune response associated with a fatal case of COVID-19 in Europe. This patient exhibited a rapid evolution towards multiorgan failure. SARS-CoV-2 was detected in multiple nasopharyngeal, blood, and pleural samples, despite antiviral and immunomodulator treatment. Clinical evolution in the blood was marked by an increase (2–3-fold) in differentiated effector T cells expressing exhaustion (PD-1) and senescence (CD57) markers, an expansion of antibody-secreting cells, a 15-fold increase in γδ T cell and proliferating NK-cell populations, and the total disappearance of monocytes, suggesting lung trafficking. In the serum, waves of a pro-inflammatory cytokine storm, Th1 and Th2 activation, and markers of T cell exhaustion, apoptosis, cell cytotoxicity, and endothelial activation were observed until the fatal outcome. This case underscores the need for well-designed studies to investigate complementary approaches to control viral replication, the source of the hyperinflammatory status, and immunomodulation to target the pathophysiological response. The investigation was conducted as part of an overall French clinical cohort assessing patients with COVID-19 and registered in clinicaltrials.gov under the following number: NCT04262921

Impact of species and antibiotic therapy of enterococcal peritonitis on 30-day mortality in critical care - An analysis of the OUTCOMEREA database

Introduction: Enterococcus species are associated with an increased morbidity in intraabdominal infections (IAI). However, their impact on mortality remains uncertain. Moreover, the influence on outcome of the appropriate or inappropriate status of initial antimicrobial therapy (IAT) is subjected to debate, except in septic shock. The aim of our study was to evaluate whether an IAT that did not cover Enterococcus spp. was associated with 30-day mortality in ICU patients presenting with IAI growing with Enterococcus spp. Material and methods: Retrospective analysis of French database OutcomeRea from 1997 to 2016. We included all patients with IAI with a peritoneal sample growing with Enterococcus. Primary endpoint was 30-day mortality. Results: Of the 1017 patients with IAI, 76 (8%) patients were included. Thirty-day mortality in patients with inadequate IAT against Enterococcus was higher (7/18 (39%) vs 10/58 (17%), p = 0.05); however, the incidence of postoperative complications was similar. Presence of Enterococcus spp. other than E. faecalis alone was associated with a significantly higher mortality, even greater when IAT was inadequate. Main risk factors for having an Enterococcus other than E. faecalis alone were as follows: SAPS score on day 0, ICU-acquired IAI, and antimicrobial therapy within 3 months prior to IAI especially with third-generation cephalosporins. Univariate analysis found a higher hazard ratio of death with an Enterococcus other than E. faecalis alone that had an inadequate IAT (HR = 4.4 [1.3-15.3], p = 0.019) versus an adequate IAT (HR = 3.1 [1.0-10.0], p = 0.053). However, after adjusting for confounders (i.e., SAPS II and septic shock at IAI diagnosis, ICU-acquired peritonitis, and adequacy of IAT for other germs), the impact of the adequacy of IAT was no longer significant in multivariate analysis. Septic shock at diagnosis and ICU-acquired IAI were prognostic factors. Conclusion: An IAT which does not cover Enterococcus is associated with an increased 30-day mortality in ICU patients presenting with an IAI growing with Enterococcus, especially when it is not an E. faecalis alone. It seems reasonable to use an IAT active against Enterococcus in severe postoperative ICU-acquired IAI, especially when a third-generation cephalosporin has been used within 3 months. © 2019 The Author(s)

Genesis of the Loma Galena Deposit, Navidad District, Patagonia Argentina

Trabajo presentado en el XV IAGOD Meeting (International Associations Genesis Ore Deposits), celebrado en Salta (Argentina), del 28 al 31 de agosto de 2018Loma Galena (6410.8 t Ag, 997,130 t Pb) is one of the eight deposits of the world class Ag + Pb ± (Cu, Zn) Navidad district (19.670 t Ag and 1.32 Mt Pb) located in the west of the North Patagonian Massif of Argentina. The deposit was formed in an active continental rift basin during the Middle Jurassic, when subaerial volcanic activity was contemporaneous with lacustrine sedimentation. The normal faults that delimited the horsts and grabens in the deposit and the Sauzal fault, a detachment fault, acted as the main conduits for the upflow of hydrothermal fluids (Fig. 1). The deposit has a lithologic control and the the highest metal anomalies are found in highly permeable and reactive autobrecciated mafic volcanoclastic rocks interbedded in the volcano-sedimentary Cañadon-Asfalto Formation (Fig. 1). The volcanic rocks are high-K basaltic andesite to dacite in composition and they have yielded LA-ICPMS U-Pb zircon ages of 173.9 ± 1.9 Ma and 170.8 ± 3.0 Ma. Lava flows surrounded by autobrecciated carapace were dominantly extruded in subaerial conditions whereas hyaloclastite and peperite facies suggest contemporaneous subaqueous volcanism synchronous with sedimentation. Lacustrine sedimentation represented by calcareous mudstone with pisolithic and laminated limestone, sandstone, chert and coal overlies the volcanic rocks. A Sr-rich evaporite layer interbeded in the sedimentary succession indicates intermittent drying out of the lake and hypersaline conditions. The mineralization occurs in veins and hydrothermal breccias that lie on the structural hanging wall and footwall of the main faults, in mineralized autobreccia and chaotic breccia in the contact between volcanic and sedimentary rocks, and disseminated in the organic-rich sedimentary rocks. The earliest infill of veins and breccias consists of calcite I and siderite with crustiform, cockade and platy textures, followed by two main episodes of mineralization. During the first stage precipitated framboidal pyrite and colloform pyrite, marcasite, galena and sphalerite. During the second stage chalcopyrite, bornite and tennantite-tetrahedrite with minor amounts of covellite and digenite replaced the early sulfides. Colloform bands of pyrite and marcasite show the highest Ag contents, although all sulfides and sulfosalts carry Ag. They are rarely observed in situ, on the walls of veins; they are usually found as transported fragments cemented by several pulses of chalcedony with minor barite. NO ENTIENDO, QUIEN? Late infill consists of calcite II, barite II, quartz and strontianite. Hydrothermal breccias present voids with a geopetal infilling with detrital material of sand-silt size and variable composition (chalcedony, quartz, calcite, ankerite, barite, galena, pyrite, marcasite, altered volcanic and sedimentary rock fragments) with parallel lamination. Volcanic rocks next to veins and breccias are altered and replaced by adularia, calcite, celadonite, quartz, and chlorite, sulfides, chalcedony, abundant clay minerals (kaolinite and smectite with minor illite-smectite mixed layers and traces of tosudite), Fe-Mg-Mn carbonates and calcite II; there are relicts of early albite. In the sedimentary rocks, the clasts are partially to completely replace by chalcedony, kaolinite and carbonates. Calcite and chalcedony also fills micro-veinlets. The sulfur isotopic signatures of sulfides hosted in veins and hydrothermal breccias (34S -0.9 to +8.3) are more restricted than the 34S of sulfides hosted in the autobreccia, chaotic breccia and sedimentary rocks (34S -15.4 to +12.9). The sulfur isotopic signature of hydrothermal barite varies between +15.7 and +22.0. The isotopic composition of celestite from the evaporite layer in the sedimentary rocks is 35.3Peer reviewe

Evidence of Ediacaran glaciation in southernmost Brazil through magmatic to meteoric fluid circulation in the porphyry-epithermal Au-Cu deposits of Lavras do Sul

International audienceThe Lavras do Sul Au-Cu mining district, southern Brazil, hosts an Ediacaran plutonic-volcanic association with hydrothermal alteration. This association is interpreted as a ca. 600-580 Ma tilted porphyry-epithermal system, where the main ore occurs in phyllic and intermediate argillic halos around quartz veins. In this paper we used detailed field mapping, fluid inclusion microthermometry, oxygen and hydrogen isotope measurements of whole-rocks, feldspars, clay minerals and quartz from propylitic, phyllic and intermediate argillic alteration to reconstruct the hydrothermal fluid temperatures and compositions. The results showed that the deeper zones of the hydrothermal system were predominantly influenced by magmatic fluid and its shallower zones by meteoric water with very negative δ18O compositions. Our data support a model of mixing between magmatic-derived fluids with meteoric waters of glacial origin. Based on stable isotope data we propose indirect evidence of high latitude position for the study area during Brasiliano/Pan-African convergence of the Kalahari and Rio de La Plata cratons

Vanadium mineralization at Los Chihuidos sediment-hosted Cu-V deposit, Neuquén Basin, Argentina: An approach to vanadium ore forming processes

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Oral probiotic treatment of Lactobacillus rhamnosus Lcr35 ® prevents visceral hypersensitivity to a colonic inflammation and an acute psychological stress

International audienceAims: This study evaluated the efficacy of a repeated oral treatment with two active pharmaceutical ingredients (Lcr Lenio (R) and Lcr Restituo (R)) derivated from the probiotic bacterial strain Lactobacillus rhamnosus Lcr35 (R) in two animal models mimicking different features of irritable bowel syndrome (IBS). IBS is characterized by visceral pain associated with alteration of bowel transit. IBS patients present visceral hypersensitivity with peripheral and central origins.Methods and Results: The injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS) into the proximal colon as well as an acute partial restraint stress (PRS) produces colonic hypersensitivity measured in conscious rats by a decrease in pain threshold in response to distal colonic distension. Visceral hypersensitivity was produced by injection of TNBS 7 days before colonic distension or by acute PRS on testing day. Treatments were performed once a day during eight consecutive days.Conclusions: This study indicates that an 8-day probiotic treatment (Lcr Lenio and Lcr Restituo) produces an antihypersensitivity activity in both TNBS and PRS visceral pain models. As this probiotic strain attenuates peripherally and centrally induced visceral hypersensitivity in rats, it may be active in treatment of IBS symptoms. An immunomodulatory effect of the probiotics was highlighted in the TNBS model on the IL-23 secretion, suggesting a mechanism of action involving a regulation of the local IL-23/Th17 immune activation.Significance and Impact of the Study: Two formulas of Lcr35 (R) probiotic strain show very encouraging results for the treatment of IBS patients. Further studies are needed to better understand the role and mechanisms of probiotics on the pathogenesis of IBS

Mineralogical signature of hydrocarbon circulation in Cretaceous red beds of the Barda Gonzalez area, Neuquen Basin, Argentina

International audienceThe Portezuelo Formation is part of a red bed sequence in the Neuquen Basin assigned to the Neuquen Group (lower Cenomanian middle Campanian). In outcrops of the Portezuelo Formation in the Barda Gonzalez region, iron oxide and hydroxide cements are only preserved in the less permeable claystone layers. Paleomigration of hydrocarbons and formation waters along the most permeable layers bleached the rocks due to partial to total dissolution of cements and grains and formation of several authigenic minerals: (1) montmorillonite and pyrite in the medium- to fine-grained sandstones and mudstones, and (2) multistage calcite and pyrite in the coarse-grained sandstones and conglomerates. The delta(ScDT)-Sc-34 (Canyon Diablo troilite) of -24.4 to 60%0 values in pyrite point to microbial reduction of a sulfate precursor. The oxidation of hydrocarbons and fluctuations in pH and carbon dioxide pressure caused by organic acids resulted in multiple stages of dissolution and precipitation of calcite. Calcite crystals host hydrocarbon-bearing fluid inclusions (+/- pyrite) with variable fluorescence color, indicating that hydrocarbon composition changed with time. The intermediate delta(CpDB)-Cp-13 (Peedee belemnite) (-8.11%0 to 8.52700) and delta(18)opDB(9.76 to 9.83700) isotope composition of calcites may have resulted from mixtures of C-13-rich CO2 after the dissolution of local calcrete with C-13-poor CO2 from oxidizing hydrocarbons. This contribution provides for the first time key information to predict the distribution of authigenic minerals in reservoir rocks in the basin and improves understanding of the diagenetic history of the Portezuelo Formation