Stock and stabilisation of organic carbon in tephra-buried volcanic soils: a case study in the northen EcuadorianAndes

Introduction : Major uncertainties in estimates of organic C trapped in soils and the mechanisms that stabilise it may impede accurate climate predictions for the future. Recent studies suggest that buried soil C represents a large and poorly constrained reservoir. In volcanic active regions, soils are repeatedly buried by tephra from explosive eruptions

An Interplay between Hypervariable Region 1 of the Hepatitis C Virus E2 Glycoprotein, the Scavenger Receptor BI, and High-Density Lipoprotein Promotes both Enhancement of Infection and Protection against Neutralizing Antibodies

Hepatitis C virus (HCV) circulates in the bloodstream in different forms, including complexes with immunoglobulins and/or lipoproteins. To address the significance of such associations, we produced or treated HCV pseudoparticles (HCVpp), a valid model of HCV cell entry and its inhibition, with naïve or patient-derived sera. We demonstrate that infection of hepatocarcinoma cells by HCVpp is increased more than 10-fold by human serum factors, of which high-density lipoprotein (HDL) is a major component. Infection enhancement requires scavenger receptor BI, a molecule known to mediate HDL uptake into cells as well as HCVpp entry, and involves conserved amino acid positions in hypervariable region 1 (HVR1) of the E2 glycoprotein. Additionally, we show that the interaction with human serum or HDL, but not with low-density lipoprotein, leads to the protection of HCVpp from neutralizing antibodies, including monoclonal antibodies and antibodies present in patient sera. Finally, the deletion or mutation of HVR1 in HCVpp abolishes infection enhancement and leads to increased sensitivity to neutralizing antibodies/sera compared to that of parental HCVpp. Altogether, these results assign to HVR1 new roles which are complementary in helping HCV to survive within its host. Besides immune escape by mutation, HRV1 can mediate the enhancement of cell entry and the protection of virions from neutralizing antibodies. By preserving a balance between these functions, HVR1 may be essential for the viral persistence of HCV

Human Serum Facilitates Hepatitis C Virus Infection, and Neutralizing Responses Inversely Correlate with Viral Replication Kinetics at the Acute Phase of Hepatitis C Virus Infection

The factors leading to spontaneous clearance of hepatitis C virus (HCV) or to viral persistence are elusive. Understanding virus-host interactions that enable acute HCV clearance is key to the development of more effective therapeutic and prophylactic strategies. Here, using a sensitive neutralization assay based on infectious HCV pseudoparticles (HCVpp), we have studied the kinetics of humoral responses in a cohort of acute-phase patients infected during a single nosocomial outbreak in a hemodialysis center. The 17 patients were monitored for the spontaneous outcome of HCV infection for 6 months before a treatment decision was made. Blood samples were taken frequently (15 ± 4 per patient). Phylogenetic analysis of the predominant virus(es) revealed infection by only one of two genotype 1b strains. While all patients seroconverted, their sera induced two opposing effects in HCVpp infection assays: inhibition and facilitation. Furthermore, the ability of sera to facilitate or inhibit infection correlated with the presence of either infecting HCV strain and divided the patients into two groups. In group 1, the progressive emergence of a relatively strong neutralizing response correlated with a fluctuating decrease in high initial viremia, leading to control of viral replication. Patients in group 2 failed to reduce viremia within the acute phase, and no neutralizing responses were detected despite seroconversion. Strikingly, sera of group 2, as well as naïve sera, facilitated infection by HCVpp displaying HCV glycoproteins from different genotypes and strains, including those retrieved from patients. These results provide new insights into the mechanisms of viral persistence and immune control of viremia

Impact of preoperative brachytherapy followed by radical hysterectomy in stage IB2 (FIGO 2018) cervical cancer: An analysis of SENTICOL I-II trials

International audienceIntroduction: The goal of this study was to compare the outcomes of preoperative brachytherapy followed by radical surgery versus radical surgery alone in cervical cancer with tumor between 2 and 4 cm (FIGO 2018 IB2). Material and methods: SENTICOL I and SENTICOL II were two French prospective multicentric trials evaluating sentinel node biopsy in early-stage cervical cancer between 2005 and 2012. Preoperative brachytherapy (low-dose rate or pulse-dose rate at the dose of 60Gy) could be performed 6 to 8 weeks prior to the radical hysterectomy, at the discretion of each center. SENTICOL I and SENTICOL II cohorts were retrospectively analysed to compare the outcomes of preoperative brachytherapy or upfront surgery in patients with IB2 cervical tumor. Results: A total of 104 patients were included: 55 underwent upfront radical hysterectomy and 49 underwent preoperative brachytherapy followed by radical hysterectomy. Patients with preoperative brachytherapy were more likely to have no residual disease (71.4% vs. 25.5%, p < 0.0001) and to be defined as low risk according to Sedlis criteria (83.3% vs. 51.2%, p < 0.0001). Adjuvant treatments were required less frequently in case of preoperative brachytherapy (14.3% vs. 54.5%, p < 0.0001). Patients with preoperative brachytherapy experienced more postoperative complications grade ≥ 3 (24.5% vs. 9.1%, p = 0.03). Patients with preoperative brachytherapy had better 5-year disease-free survival compared to patients who underwent surgery alone, 93.6% and 74.4% respectively (p = 0.04). Conclusion: Although preoperative brachytherapy was significantly associated with more severe postoperative complications, better pathologic features were obtained on surgical specimens and led to a better 5-year disease-free survival in IB2 cervical cancer

The Clinical Spectrum and Therapeutic Management of Hypocomplementemic Urticarial Vasculitis: Data From a French Nationwide Study of Fifty‐Seven Patients

International audienceOBJECTIVE:Hypocomplementemic urticarial vasculitis (HUV) is an uncommon vasculitis of unknown etiology that is rarely described in the literature. We undertook this study to analyze the clinical spectrum and the therapeutic management of patients with HUV.METHODS:We conducted a French nationwide retrospective study that included 57 patients with chronic urticaria, histologic leukocytoclastic vasculitis, and hypocomplementemia. We assessed clinical and laboratory data and evaluated the patients' cutaneous and immunologic responses to therapy. We evaluated treatment efficacy by measuring the time to treatment failure.RESULTS:Urticarial lesions were typically more pruritic than painful and were associated with angioedema in 51% of patients, purpura in 35%, and livedo reticularis in 14%. Extracutaneous manifestations included constitutional symptoms (in 56% of patients) as well as musculoskeletal involvement (in 82%), ocular involvement (in 56%), pulmonary involvement (in 19%), gastrointestinal involvement (in 18%), and kidney involvement (in 14%). Patients with HUV typically presented with low C1q levels and normal C1 inhibitor levels, in association with anti-C1q antibodies in 55% of patients. Hydroxychloroquine or colchicine seemed to be as effective as corticosteroids as first-line therapy. In patients with relapsing and/or refractory disease, rates of cutaneous and immunologic response to therapy seemed to be higher with conventional immunosuppressive agents, in particular, azathioprine, mycophenolate mofetil, or cyclophosphamide, while a rituximab-based regimen tended to have higher efficacy. Finally, a cutaneous response to therapy was strongly associated with an immunologic response to therapy.CONCLUSION:HUV represents an uncommon systemic and relapsing vasculitis with various manifestations, mainly, musculoskeletal and ocular involvement associated with anti-C1q antibodies, which were found in approximately half of the patients. The best strategy for treating HUV has yet to be defined

Fractional Flow Reserve to Guide Treatment of Patients With Multivessel Coronary Artery Disease

International audienc