Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapy

Background & aims: HCV CD4+ and CD8+ specific T cells responses are functionally impaired during chronic hepatitis C infection. DAAs therapies eradicate HCV infection in more than 95% of treated patients. However, the impact of HCV elimination on immune responses remain controversial. Here, we aimed to investigate whether HCV cure by DAAs could reverse the impaired immune response to HCV. Methods: We analyzed 27 chronic HCV infected patients undergoing DAA treatment in tertiary care hospital, and we determined the phenotypical and functional changes in both HCV CD8+ and CD4+ specific T-cells before and after viral clearance. PD-1, TIM-3 and LAG-3 cell-surface expression was assessed by flow cytometry to determine CD4+ T cell exhaustion. Functional responses to HCV were analyzed by IFN-Ɣ ELISPOT, intracellular cytokine staining (IL-2 and IFN-Ɣ) and CFSE-based proliferation assays. Results: We observed a significant decrease in the expression of PD-1 in CD4+ T-cells after 12 weeks of viral clearance in non-cirrhotic patients (p = 0.033) and in treatment-naive patients (p = 0.010), indicating a partial CD4 phenotype restoration. IFN-Ɣ and IL-2 cytokines production by HCV-specific CD4+ and CD8+ T cells remained impaired upon HCV eradication. Finally, a significant increase of the proliferation capacity of both HCV CD4+ and CD8+ specific T-cells was observed after HCV elimination by DAAs therapies. Conclusions: Our results show that in chronically infected patients HCV elimination by DAA treatment lead to partial reversion of CD4+ T cell exhaustion. Moreover, proliferative capacity of HCV-specific CD4+ and CD8+ T cells is recovered after DAA's therapies

Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapy

Fibrosi hepàtica; Cèl·lules T; Teràpia de citocinesFibrosis hepática; Células T; Terapia de citocinasLiver fibrosis; T cells; Cytokine therapyBackground & aims HCV CD4+ and CD8+ specific T cells responses are functionally impaired during chronic hepatitis C infection. DAAs therapies eradicate HCV infection in more than 95% of treated patients. However, the impact of HCV elimination on immune responses remain controversial. Here, we aimed to investigate whether HCV cure by DAAs could reverse the impaired immune response to HCV. Methods We analyzed 27 chronic HCV infected patients undergoing DAA treatment in tertiary care hospital, and we determined the phenotypical and functional changes in both HCV CD8+ and CD4+ specific T-cells before and after viral clearance. PD-1, TIM-3 and LAG-3 cell-surface expression was assessed by flow cytometry to determine CD4+ T cell exhaustion. Functional responses to HCV were analyzed by IFN-Ɣ ELISPOT, intracellular cytokine staining (IL-2 and IFN-Ɣ) and CFSE-based proliferation assays. Results We observed a significant decrease in the expression of PD-1 in CD4+ T-cells after 12 weeks of viral clearance in non-cirrhotic patients (p = 0.033) and in treatment-naive patients (p = 0.010), indicating a partial CD4 phenotype restoration. IFN-Ɣ and IL-2 cytokines production by HCV-specific CD4+ and CD8+ T cells remained impaired upon HCV eradication. Finally, a significant increase of the proliferation capacity of both HCV CD4+ and CD8+ specific T-cells was observed after HCV elimination by DAAs therapies. Conclusions Our results show that in chronically infected patients HCV elimination by DAA treatment lead to partial reversion of CD4+ T cell exhaustion. Moreover, proliferative capacity of HCV-specific CD4+ and CD8+ T cells is recovered after DAA’s therapies.This study was funded by Instituto de Salud Carlos III, cofinanced by the European Regional Development Fund (ERDF): grant numbers PI16/00337, PI18/00210 and PI19/00301. C.P. is supported by the Miguel Servet program of the Instituto de Salud Carlos III (CP14/00121 and CPII19/00001) cofinanced by the European Regional Development Fund (ERDF)

Co-occurrence of colistin-resistance genes mcr-1 and mcr-3 among multidrug-resistant Escherichia coli isolated from cattle, Spain, September 2015

Los genes de resistencia a colistina mcr-3 y mcr-1 se detectaron en un aislado de Escherichia coli de heces de ganado en un matadero español en 2015. Las secuencias de ambos genes se hibridaron a la misma banda de plásmidos de aproximadamente 250 kb, aunque la resistencia a la colistina no fue movilizable . El aislado producía betalactamasas de espectro extendido y pertenecía al serotipo O9: H10 y al tipo de secuencia ST533. Aquí informamos un gen mcr-3 detectado en Europa después de informes anteriores de Asia y los Estados Unidos.Colistin resistance genes mcr-3 and mcr-1 have been detected in an Escherichia coli isolate from cattle faeces in a Spanish slaughterhouse in 2015. The sequences of both genes hybridised to same plasmid band of ca 250 kb, although colistin resistance was non-mobilisable. The isolate was producing extended-spectrum beta-lactamases and belonged to serotype O9:H10 and sequence type ST533. Here we report an mcr-3 gene detected in Europe following earlier reports from Asia and the United States.• Ministerio de Economía, Industria y Competitividad. Proyecto AGL2016- 74882-C3 • Ministerio de Agricultura y Pesca (España) y Comunidad Autónoma de Comunidad Autónoma de Madrid. Ayuda S2013 / ABI-2747 • Junta de Extremadura y Fondo Europeo de Desarrollo Regional. Ayuda GR15075 e IB16073 • Fundación para la Ciencia y la Tecnología (Portugal). Ayudas UID / MAR / 04292/2013 • Fundación Tatiana de Guzmán El Bueno (España). Beca doctoral para María del Rocío Iglesias Parro • Instituto Nacional de Agricultura y Alimentación. Investigación y Tecnología (INIA). Beca doctoral para María del Rocío Iglesias Parro • Ministerio de Economía, Industria y Competitividad. Beca FPI2014-020, para Narciso Martín QuijadapeerReviewe

Inter-Rater Variability in the Evaluation of Lung Ultrasound in Videos Acquired from COVID-19 Patients

12 páginas, 7 figuras, 1 tablaLung ultrasound (LUS) allows for the detection of a series of manifestations of COVID-19, such as B-lines and consolidations. The objective of this work was to study the inter-rater reliability (IRR) when detecting signs associated with COVID-19 in the LUS, as well as the performance of the test in a longitudinal or transverse orientation. Thirty-three physicians with advanced experience in LUS independently evaluated ultrasound videos previously acquired using the ULTRACOV system on 20 patients with confirmed COVID-19. For each patient, 24 videos of 3 s were acquired (using 12 positions with the probe in longitudinal and transverse orientations). The physicians had no information about the patients or other previous evaluations. The score assigned to each acquisition followed the convention applied in previous studies. A substantial IRR was found in the cases of normal LUS (κ = 0.74), with only a fair IRR for the presence of individual B-lines (κ = 0.36) and for confluent B-lines occupying 50% (κ = 0.50). No statistically significant differences between the longitudinal and transverse scans were found. The IRR for LUS of COVID-19 patients may benefit from more standardized clinical protocols.This research was partially funded by CDTI (Spanish acronym: Centre for Industrial Tech- nological Development), funding number COI-20201153. Partially supported by the Google Cloud Research Credits program with the funding number GCP19980904, by the project RTI2018-099118- A-I00 founded by MCIU/AEI/FEDER UE and by the European Commission–NextGenerationEU, through CSIC’s Global Health Platform (PTI Salud Global)

Barriers to the Practice of Sport and Physical Activity from the Perspective of Self-Determination Theory

The practice of sport and physical activity can be hampered by the presence of amotivation, the frustration of basic psychological needs, and barriers to carrying out that practice. Based on the principles of self-determination theory (SDT), the objective of this study was to analyze the relationship of these variables and assess differences based on age, sex, residential independence, academic/employment situation, and prior sport and physical activity. The sample comprised 102 individuals, aged between 18 and 25 (M = 21.61; SD = 2.04), who completed the Behavioral Regulation in Exercise Questionnaire, the Frustration of Psychological Needs in Physical Exercise Scale, and the Self-Perceived Barriers of Physical Activity Questionnaire. Our results showed that participants had high values of controlled motivation, the frustration of the basic psychological need for competence, and high values for the barrier of obligations/lack of time. We found a significant and positive association between the frustration of the basic psychological need for competence and the barriers present in the practice of physical activity. Moreover, we found that women reported experiencing body image/anxiety as a barrier to practicing sport and physical activity more than men and individuals aged 22–25 years experiencing obligations/lack of time as a barrier more than the those aged 18 to 21 years. Practical applications were proposed to avoid the frustration of basic psychological needs, increase the most self-determined forms of motivation, and reduce barriers to the practice of sport and physical activity

Novel antimicrobial phosphate-free glass–ceramic scaffolds for bone tissue regeneration

In this study a phosphate-free glass–ceramic porous scaffold was synthesized by a three-step methodology involving slurry preparation, induction of porosity by surfactant-assisted foaming following by freeze-drying and sintering. This inorganic scaffold was characterized by X-ray diffraction, scanning electron microscope (SEM), degradation and bioactivity. Thermal treatment at 750 °C showed two new crystalline phases, combeite and nepheline, into the glassy matrix responsible for its properties. The cell response of the scaffold was also evaluated for using as a bone graft substitute. A commercial Biphasic Calcium Phosphate, BCP, scaffold was assessed in parallel as reference material. Microstructures obtained by SEM showed the presence of macro, meso and microporosity. The glass–ceramic scaffold possesses an interconnected porosity around 31% with a crack-pore system that promote the protein adsorption and cell attachment. Glass–ceramic scaffold with high concentration of calcium ions shows an antimicrobial behavior against Escherichia coli after 24 h of contact. Nepheline phase present in the glass–ceramic structure is responsible for its high mechanical properties being around 87 MPa. Glass–ceramic scaffold promotes greater protein adsorption and therefore the attachment, spreading and osteodifferentiation of Adipose Derived Stem Cells than BCP scaffold. A higher calcification was induced by glass–ceramic scaffold compared to reference BCP material.The authors acknowledge the Principado de Asturias for funding through the projects GRUPIN IDI/2018/000232.Peer reviewe

Prevention of periodontitis by the addition of a bactericidal particulate glass/glass-ceramic to a dental resin: a pilot study in dogs

The aim of the study is to evaluate, in a ligature-induced periodontitis model, the efficacy of a commercially available dental resin containing different antimicrobial glass/glass-ceramic additions (0–26 wt.%). It has been proved that a 26 wt.% glass addition to a conventional dental resin matrix does not alter neither its workability nor its adhesion to the surface of teeth; however, it does confer notable antimicrobial properties when tested in vitro. Moreover, in vivo tests in Beagle dogs demonstrated the prevention of bone loss in ligature-induced plaque accumulation around teeth. Particularly, the glass-ceramic filler resin composite has shown excellent antimicrobial control since it displays the same bone loss as that of the negative control. The results obtained in the present investigation have shown that a conventional dental resin containing a fraction of glass/glass-ceramic (≥26 wt.%) can prevent periodontitis, which is considered to be a most serious dental disease

ICLUEX Integración de Contenidos y Lengua Extranjera en la Universidad de Extremadura : guía sobre recursos para el desarrollo de destrezas académicas en la enseñanza-aprendizaje a través del inglés

Se presentan parte de los resultados de la investigación: 'Diseño de entornos virtuales de aprendizaje colaborativo para la enseñanza integrada de contenidos y lenguas extranjeras (AICLE) en la Educación Superior adaptados a la Universidad de Extremadura (ICLUEX)', financiada por la Junta de Extremadura y llevada a cabo por La Unviersidad de Extremadura entre los cursos académicos 2018-2019 y 2021-2022, cuyo objetivo era realizar una aportación al proceso de enseñanza-aprendizaje de contenidos disciplinares a través del inglés. Con la investigación se pretendía identificar las necesidades lingüísticas del alumnado de materias impartidas en inglés y desarrollar contenidos en entornos virtuales de aprendizaje colaborativo para la enseñanza integrada de contenidos y lenguas extranjeras adaptados a la Universidad de Extremadura. Los objetivos específicos del proyecto fueron: hacer accesibles los materiales al profesorado que imparte su docencia en inglés al alumnado que los pueda necesitar, colaborar en el desarrollo de la competencia lingüística en inglés del alumnado de la Universidad de Extremadura, contribuir con la política de internacionalización de la Universidad de Extremadura y establecer una red de conocimiento y de recursos con otras instituciones de Educación Superior europeas. Se recogen los materiales docentes elaborados y se aclaran los principios bajo los que se han desarrolladoES