Rapid decrease in titer and breadth of neutralizing anti-HCV antibodies in HIV/HCV-coinfected patients who achieved SVR

The main targets for neutralizing anti-hepatitis C virus (HCV) antibodies (HCV-nAbs) are the E1 and E2 envelope glycoproteins. We have studied the characteristics of HCV-nAbs through a retrospective study involving 29 HIV/HCV-coinfected patients who achieved sustained virological response (SVR) with pegIFNα+ribavirin anti-HCV therapy. Plasma samples at baseline and week 24 after SVR were used to perform neutralization assays against fve JFH1-based HCV recombinant viruses coding for E1 and E2 from genotypes 1a (H77), 1b (J4), 2a (JFH1), 3a (S52) and 4a (ED43). At baseline, the majority of plasma samples neutralized 1a, 1b, 2a, and 4a, but not 3a, genotypes. Twenty-four weeks following SVR, most neutralizing titers declined substantially. Furthermore, titers against 3a and 2a were not detected in many patients. Plasma samples with high HCV-nAb titers neutralized all genotypes, and the highest titers at the starting point correlated with the highest titers at week 24 after SVR. In conclusion, high titers of broad-spectrum HCV-nAbs were detected in HIV/HCV-coinfected individuals, however, those titers declined soon after SVRThis study was supported by grants from Instituto de Salud Carlos III (ISCIII; grant numbers PI14/01094 and PI17/00657 to JB, PI17/00903 to JGG, PI14CIII/00011 and PI17CIII/00003 to SR) and Ministerio de Sanidad, Servicios Sociales e Igualdad (grant number EC11-241). Te study was also funded by the RD16CIII/0002/0002, RD16/0025/0018, and RD16/0025/0017 projects as part of the Plan Nacional R+D+I and co-funded by ISCIII- Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER

Rapid decrease in titer and breadth of neutralizing anti-HCV antibodies in HIV/HCV-coinfected patients who achieved SVR

Sustained virological response (SVR); Anti-HCV therapy; HIV/HCV-coinfected patientsRespuesta virológica sostenida (RVS); Terapia anti-VHC; Pacientes coinfectados por VIH/VHCResposta virològica sostinguda (RVS); Teràpia anti-VHC; Pacients infectats amb VIH/VHCThe main targets for neutralizing anti-hepatitis C virus (HCV) antibodies (HCV-nAbs) are the E1 and E2 envelope glycoproteins. We have studied the characteristics of HCV-nAbs through a retrospective study involving 29 HIV/HCV-coinfected patients who achieved sustained virological response (SVR) with peg-IFNα + ribavirin anti-HCV therapy. Plasma samples at baseline and week 24 after SVR were used to perform neutralization assays against five JFH1-based HCV recombinant viruses coding for E1 and E2 from genotypes 1a (H77), 1b (J4), 2a (JFH1), 3a (S52) and 4a (ED43). At baseline, the majority of plasma samples neutralized 1a, 1b, 2a, and 4a, but not 3a, genotypes. Twenty-four weeks following SVR, most neutralizing titers declined substantially. Furthermore, titers against 3a and 2a were not detected in many patients. Plasma samples with high HCV-nAb titers neutralized all genotypes, and the highest titers at the starting point correlated with the highest titers at week 24 after SVR. In conclusion, high titers of broad-spectrum HCV-nAbs were detected in HIV/HCV-coinfected individuals, however, those titers declined soon after SVR.The HIV BioBank, integrated in the Spanish AIDS Research Network, is supported by the Institute of Health Carlos III, ISCIII, Spanish Health Ministry (Grant nº RD06/0006/0035 and RD12/0017/0037) as part of the State Plan for Scientific and Technical Research and Innovation and co-financed by ISCIII- Sub-Directorate General for Research Assessment and Promotion and European Regional Development Fund (ERDF) and Foundation for Research and Prevention of AIDS in Spain (FIPSE). The RIS Cohort (CoRIS) is funded by the ISCIII through the Spanish AIDS Research Network (RIS C03/173 and RD12/0017/0018) as part of the State Plan for Scientific and Technical Research and Innovation and co-financed by ISCIII- Sub-Directorate General for Research Assessment and Promotion and European Regional Development Fund (ERDF). This study was supported by grants from Instituto de Salud Carlos III (ISCIII; grant numbers PI14/01094 and PI17/00657 to JB, PI17/00903 to JGG, PI14CIII/00011 and PI17CIII/00003 to SR) and Ministerio de Sanidad, Servicios Sociales e Igualdad (grant number EC11-241). The study was also funded by the RD16CIII/0002/0002, RD16/0025/0018, and RD16/0025/0017 projects as part of the Plan Nacional R + D + I and co-funded by ISCIII- Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER). JB is an investigator from the Programa de Intensificación de la Actividad Investigadora en el Sistema Nacional de Salud (I3SNS), Refs INT15/00079 and INT16/00100

Provirus reactivation is impaired in HIV-1 infected individuals on treatment with dasatinib and antiretroviral therapy

The latent viral reservoir formed by HIV-1, mainly in CD4 + T cells, is responsible for the failure of antiretroviral therapy (ART) to achieve a complete elimination of the virus in infected individuals. We previously determined that CD4 + T cells from individuals with chronic myeloid leukemia (CML) on treatment with dasatinib are resistant to HIV-1 infection ex vivo. The main mechanism for this antiviral effect is the preservation of SAMHD1 activity. In this study, we aimed to evaluate the impact of dasatinib on the viral reservoir of HIV-infected individuals with CML who were on simultaneous treatment with ART and dasatinib. Due to the low estimated incidence of HIV-1 infection and CML (1:65,000), three male individuals were recruited in Spain and Germany. These individuals had been on treatment with standard ART and dasatinib for median 1.3 years (IQR 1.3-5.3 years). Reservoir size and composition in PBMCs from these individuals was analyzed in comparison with HIV-infected individuals on triple ART regimen and undetectable viremia. The frequency of latently infected cells was reduced more than 5-fold in these individuals. The reactivation of proviruses from these cells was reduced more than 4-fold and, upon activation, SAMHD1 phosphorylation was reduced 40-fold. Plasma levels of the homeostatic cytokine IL-7 and CD4 effector subpopulations TEM and TEMRA in peripheral blood were also reduced. Therefore, treatment of HIV-infected individuals with dasatinib as adjuvant of ART could disturb the reservoir reactivation and reseeding, which might have a beneficial impact to reduce its size

Fatigue behavior of adhesive joints under modes I and II fracture in carbon-epoxy composites, influence of exposure time in a saline environment

This work investigates the fatigue crack growth behavior of adhesive joints under pure modes I and II within epoxy matrix composites reinforced with unidirectional carbon fibers. Experimental tests are made using Double Cantilever Beam (DCB) and End-Notched Flexure (ENF) setups for modes I and II respectively, considering exposure periods of one week and twelve weeks in a salt spray chamber. Control specimens are also studied for comparison.Static tests were conducted to securely establish the levels of Energy Release Rate (ERR) that were subsequently used to obtain the fatigue initiation curves (G-N) and fatigue crack growth curves (G-da/dN). A probabilistic model based on a Weibull distribution is applied to analyze fatigue initiation data.The fatigue limit in mode I, for all aging periods, is around 25 % of the static strength, while in mode II, it is around 20 %. These results are very close at all aging levels (0, 1, and 12 weeks). From this, it is inferred that aging in a saline environment of the studied joints does not have a significant impact on the fatigue limit.In the crack growth zone, for mode I, the velocity is higher in the specimens aged in both periods than in the unaged specimens. The same cannot be said for mode II, where a clear trend cannot be appreciated

Patterns of movement of released female brown bears in the Cantabrian Mountains, northwestern Spain

Between 2008 and 2013, 3 female brown bears (Ursus arctos; 2 cubs-of-the-year and 1 2-yr-old) were rescued, rehabilitated in captivity, radiotagged, and released back to the Cantabrian Mountains, northwestern Spain. We characterized their daily and seasonal movements post-release to gain insights into their movement strategies and the viability of bears released in human-dominated environments. The bears exhibited marked diurnal activity and were active throughout winter. Two bears demonstrated behaviors similar to those reported for wild bears, whereas one cub-of-the-year was recaptured after 21 days because she developed signs of habituation to humans.Peer reviewe

Regeneration of alveolar ridge defects. Consensus report of group 4 of the 15th European Workshop on Periodontology on Bone Regeneration

BACKGROUND AND AIMS Bone augmentation procedures to enable dental implant placement are frequently performed. The remit of this working group was to evaluate the current evidence on the efficacy of regenerative measures for the reconstruction of alveolar ridge defects. MATERIAL AND METHODS The discussions were based on four systematic reviews focusing on lateral bone augmentation with implant placement at a later stage, vertical bone augmentation, reconstructive treatment of peri-implantitis associated defects, and long-term results of lateral window sinus augmentation procedures. RESULTS A substantial body of evidence supports lateral bone augmentation prior to implant placement as a predictable procedure in order to gain sufficient ridge width for implant placement. Also, vertical ridge augmentation procedures were in many studies shown to be effective in treating deficient alveolar ridges to allow for dental implant placement. However, for both procedures the rate of associated complications was high. The adjunctive benefit of reconstructive measures for the treatment of peri-implantitis-related bone defects has only been assessed in a few RCTs. Meta-analyses demonstrated a benefit with regard to radiographic bone gain but not for clinical outcomes. Lateral window sinus floor augmentation was shown to be a reliable procedure in the long term for the partially and fully edentulous maxilla. CONCLUSIONS The evaluated bone augmentation procedures were proven to be effective for the reconstruction of alveolar ridge defects. However, some procedures are demanding and bear a higher risk for post-operative complications

Regeneration of alveolar ridge defects. Consensus report of group 4 of the 15th European Workshop on Periodontology on Bone Regeneration

BACKGROUND AND AIMS: Bone augmentation procedures to enable dental implant placement are frequently performed. The remit of this working group was to evaluate the current evidence on the efficacy of regenerative measures for the reconstruction of alveolar ridge defects. MATERIAL AND METHODS: The discussions were based on four systematic reviews focusing on lateral bone augmentation with implant placement at a later stage, vertical bone augmentation, reconstructive treatment of peri-implantitis associated defects, and long-term results of lateral window sinus augmentation procedures. RESULTS: A substantial body of evidence supports lateral bone augmentation prior to implant placement as a predictable procedure in order to gain sufficient ridge width for implant placement. Also, vertical ridge augmentation procedures were in many studies shown to be effective in treating deficient alveolar ridges to allow for dental implant placement. However, for both procedures the rate of associated complications was high. The adjunctive benefit of reconstructive measures for the treatment of peri-implantitis-related bone defects has only been assessed in a few RCTs. Meta-analyses demonstrated a benefit with regard to radiographic bone gain but not for clinical outcomes. Lateral window sinus floor augmentation was shown to be a reliable procedure in the long-term for the partially and fully edentulous maxilla. CONCLUSIONS: The evaluated bone augmentation procedures were proven to be effective for the reconstruction of alveolar ridge defects. However, some procedures are demanding and bear a higher risk for postoperative complications. This article is protected by copyright. All rights reserved