Antivirales de acción directa: la nueva era del tratamiento de la hepatitis C. Desde el interferón hasta la eliminación.

Hepatitis C virus (HCV) is a RNA virus, parenteral transmitted that, after an acute infection, becomes chronic in 75% of the cases. Chronic infection presents risk of cirrhosis progression and cirrhosis complications such as ascites, encephalopathy, variceal bleeding or hepatocellular carcinoma. Hepatitis C treatment has evolved in the last years. In 1984, patients were treated with interferon (INF), a subcutaneous administrated drug with high number of adverse events and low rates of sustained virological response (SVR). Some years later, this treatment was modified to pegilated-INF and ribavirin (RBV), that partially improve SVR but with similar adverse events. The hepatitis C treatment revolution happened in 2011 with the introduction of the first direct-acting antiviral (DAA), oral administrated, firstly prescribed together with INF and RBV (triple therapy). Although SVR rates were higher, adverse events were still important. Subsequently, DAA were used in therapies free of INF and later, also free of RBV, with high rates of SVR and with barely adverse events. Furthermore, the management of patients was also changing during those years. Thanks to the introduction of non-invasive methods to estimate liver fibrosis before treatment, liver biopsy became unnecessary. For all the previously mentioned, we came up with 4 hypothesis that are the aims of each article that are included in this thesis: - To evaluate the impact of triple therapy on liver fibrosis measured by transient elastography after SVR. - To investigated the real-world effectiveness and safety of INF-free treatments. - To analyse laboratory parameters, clinical and fibrosis long-term evolution in patients with advanced fibrosis cured with DAA. - To evaluate the results of a hepatitis C screening program in hospitalized COVID-19 patients. The conclusions of the aforementioned articles are: - SVR achieved with triple therapy produce a fast and significant reduction of the transient elastpgraphy values. - DAA in INF-free therapies administrated in a real-world setting present a high SVR with a low rate of adverse events. - In patients with advanced fibrosis or cirrhosis exist a rapid and long-lasting improvement of laboratory parameters and also and improvement of the liver fibrosis measured by non-invasive methods, but the risk of decompensation and apparition of hepatocellular carcinoma is not eliminate, so long-term monitoring is need. - Finally, HCV screening in hospitalized COVID-19 patients prove a lower prevalence of active hepatitis C than the expected, so nowadays, general screening in patients without risk factors is not justified.El virus de la hepatitis C (VHC) es un virus ARN de transmisión parenteral que, tras la infección aguda, se cronifica hasta en el 75% de los casos. Es esta infección crónica la que presenta riesgo de progresión a cirrosis, pudiendo aparecer complicaciones como descompensaciones de la cirrosis (ascitis, encefalopatía, hemorragia por varices) o incluso hepatocarcinoma. El tratamiento de la hepatitis C ha sufrido grandes cambios en los últimos años. Inicialmente, en 1984, los pacientes se trataban con interferón (INF), un fármaco de administración subcutánea, con muchos efectos adversos y bajas tasas de respuesta virológica sostenida (RVS). Años más tarde este tratamiento se modificó a INF-pegilado y ribavirina (RBV), que mejoraba parcialmente la RVS pero con los mismos efectos secundarios. La revolución del tratamiento para la hepatitis C se inició en 2011 con la aparición de los primeros antivirales de acción directa (AAD), de administración oral, que inicialmente se administraban conjuntamente con INF y RBV (lo que se conoce como triple terapia). A pesar de presentar mejores tasas de RVS, los efectos secundarios eran notables. Posteriormente se iniciaron las terapias con AAD libres de INF y más tarde también libres de RBV, con una alta tasa de RVS y sin apenas efectos adversos. Además el manejo de estos pacientes también fue variando durante esos años, gracias a la aparición y validación de métodos no invasivos para la estimación de la fibrosis hepática pretratamiento por lo que la biopsia hepática dejó de ser necesaria. Con estos precedentes nos planteamos cuatro hipótesis que son los objetivos de cada uno de los artículos que comprenden esta tesis: - Valorar la evolución de la fibrosis hepática con elastografía de transición tras la RVS conseguida con triple terapia. - Evaluar la RVS y el perfil de seguridad de los AAD en terapias libres de INF en vida real. - Valorar la evolución clínica, analítica y de la fibrosis a largo plazo de los pacientes con fibrosis avanzada que presentaban RVS tras el tratamiento con AAD en terapias libres de INF. - Estimar la prevalencia de la infección por VHC en nuestro medio a través del cribado de los pacientes que ingresaban en el hospital por COVID-19. De los trabajos realizados se concluye que: - La RVS conseguida tras tratamiento con triple terapia produce una disminución rápida y significativa de los valores de la elastografía de transición. - Los AAD en terapias libres de INF en vida real presentan una alta RVS con una baja tasa de efectos adversos. - En los pacientes con fibrosis avanzada o cirrosis existe una mejoría rápida y duradera de los parámetros analíticos además de una mejoría de la fibrosis hepática medida por métodos no invasivos, pero sin conseguir eliminar completamente el riesgo de descompensación y de aparición de hepatocarcinoma, por lo que es preciso realizar seguimiento a estos pacientes. - Por último, el cribado del VHC en los pacientes ingresados por COVID-19 durante la pandemia demostró una prevalencia de hepatitis C activa menor de la esperada, por lo que el cribado en población general sin factores de riesgo actualmente no está justificado.Escuela de DoctoradoDoctorado en Investigación en Ciencias de la Salu

La captivitat dels dofins

Treball presentat a l'assignatura de Deontologia i Veterinària Legal (21223

Nexo agua-energía: desde el nacimiento del río Llobregat hasta Manresa

En este trabajo se estudia el nexo agua-energía en el tramo del río Llobregat desde Castellar de N’hug hasta Manresa. Se lleva a cabo una evaluación de la cantidad de energía necesaria en las estaciones potabilizadoras y depuradoras para adecuar el agua del río, además de determinar la cantidad de energía que generan las centrales mini-hidroeléctricas. Estos dos valores de energía finales son comparados para demostrar si se consume más energía que la que se genera, o al contrario. Se estudia la necesidad de agua para la producción de energía a partir de las centrales mini-hidroeléctricas, es decir, aquellas centrales que tienen una potencia instalada de entre 100 i 1.000 kW ya que son las que mayoritariamente, encontramos en este tramo del río. Así mismo, también se estudia la necesidad o consumo de energía para la depuración y el acondicionamiento del agua, teniendo como base los procesos de depuración y potabilización del agua. Para ello, se analizan las tendencias de consumos energéticos de las EDAR, así como de las ETAP y se intenta encontrar una relación entre el caudal de agua tratado y el consumo energético en ambos casos. Además, a partir del ratio con unidades kWh/m3 (cantidad de energía producida o consumida por unidad de volumen de agua), se puede conocer por un lado, si las EDAR y las ETAP tienen mayor o menor consumo por unidad de agua tratada y por otro lado, si las mini-hidroeléctricas necesitan más o menos cantidad de agua para producir energía

The Cortical Actin Determines Different Susceptibility of Naïve and Memory CD4+ T Cells to HIV-1 Cell-to-Cell Transmission and Infection

Memory CD4+ T cells are preferentially infected by HIV-1 compared to naïve cells. HIV-1 fusion and entry is a dynamic process in which the cytoskeleton plays an important role by allowing virion internalization and uncoating. Here, we evaluate the role of the cortical actin in cell-to-cell transfer of virus antigens and infection of target CD4+ T cells. Using different actin remodeling compounds we demonstrate that efficiency of HIV-internalization was proportional to the actin polymerization of the target cell. Naïve (CD45RA+) and memory (CD45RA−) CD4+ T cells could be phenotypically differentiated by the degree of cortical actin density and their capacity to capture virus. Thus, the higher cortical actin density of memory CD4+ T cells was associated to increased efficiency of HIV-antigen internalization and the establishment of a productive infection. Conversely, the lower cortical actin density in naïve CD4+ T cells restricted viral antigen transfer and consequently HIV-1 infection. In conclusion, the cortical actin density differentially affects the susceptibility to HIV-1 infection in naïve and memory CD4+ T cells by modulating the efficiency of HIV antigen internalization

FÒRUM de joves talents: un escenari no formal d’ensenyament/aprenentatge

Peer ReviewedPostprint (published version

Les metadades als dipòsits digitals de la Universitat Politècnica de Catalunya

Presentació de la sessió professional "Dipòsits digitals i metadades", celebrada a la Biblioteca de Catalunya el 16 de setembre de 200

Numerical modelling and experimental validation in Selective Laser Melting

In this work a finite-element framework for the numerical simulation of the heat transfer analysis of additive manufacturing processes by powder-bed technologies, such as Selective Laser Melting, is presented. These kind of technologies allow for a layer-by-layer metal deposition process to cost-effectively create, directly from a CAD model, complex functional parts such as turbine blades, fuel injectors, heat exchangers, medical implants, among others. The numerical model proposed accounts for different heat dissipation mechanisms through the surrounding environment and is supplemented by a finite-element activation strategy, based on the born-dead elements technique, to follow the growth of the geometry driven by the metal deposition process, in such a way that the same scanning pattern sent to the numerical control system of the AM machine is used. An experimental campaign has been carried out at the Monash Centre for Additive Manufacturing using an EOSINT-M280 machine where it was possible to fabricate different benchmark geometries, as well as to record the temperature measurements at different thermocouple locations. The experiment consisted in the simultaneous printing of two walls with a total deposition volume of 107 cm3 in 992 layers and about 33,500 s build time. A large number of numerical simulations have been carried out to calibrate the thermal FE framework in terms of the thermophysical properties of both solid and powder materials and suitable boundary conditions. Furthermore, the large size of the experiment motivated the investigation of two different model reduction strategies: exclusion of the powder-bed from the computational domain and simplified scanning strategies. All these methods are analysed in terms of accuracy, computational effort and suitable application

Predictors of mortality among elderly dependent home care patients

BACKGROUND: The purpose of this study is to identify which variables –among those commonly available and used in the primary care setting– best predict mortality in a cohort of elderly dependent patients living at home (EDPLH) that were included in a home care program provided by Primary Care Teams (PCT). Additionally, we explored the risk of death among a sub-group of these patients that were admitted to hospital the year before they entered the home care program. METHODS: A one-year longitudinal cohort study of a sample of EDPLH patients included in a home care programme provided by 72 PCTs. Variables collected from each individual patient included health and social status, carer’s characteristics, carer’s burden of care, health and social services received. RESULTS: 1,001 patients completed the study (91.5%), 226 were admitted to hospital the year before inclusion. 290 (28.9%) died during the one-year follow-up period. In the logistic regression analysis women show a lower risk of death [OR= 0.67 (0.50-0.91)]. The risk of death increases with comorbidity [Charlson index OR= 1.14 (1,06-1.23)], the number of previous hospital admissions [OR= 1,16 (1.03-1.33)], and with the degree of pressure ulcers [ulcers degree 1–2 OR = 2.94 (1.92-4.52); ulcers degree 3–4 OR = 4.45 (1.90-10.92)]. The logistic predictive model of mortality for patients previously admitted to hospital identified male sex, comorbidity, degree of pressure ulcers, and having received home care rehabilitation as independent variables that predict death. CONCLUSIONS: Comorbidity, hospital admissions and pressure ulcers predict mortality in the following year in EDPLH patients. The subgroup of patients that entered home care programs with a previous record of hospital admission and a high score in our predictive model might be considered as candidates for palliative care

The G1/S Specific Cyclin D2 Is a Regulator of HIV-1 Restriction in Non-proliferating Cells

Macrophages are a heterogeneous cell population strongly influenced by differentiation stimuli that become susceptible to HIV-1 infection after inactivation of the restriction factor SAMHD1 by cyclin-dependent kinases (CDK). Here, we have used primary human monocyte-derived macrophages differentiated through different stimuli to evaluate macrophage heterogeneity on cell activation and proliferation and susceptibility to HIV-1 infection. Stimulation of monocytes with GM-CSF induces a non-proliferating macrophage population highly restrictive to HIV-1 infection, characterized by the upregulation of the G1/S-specific cyclin D2, known to control early steps of cell cycle progression. Knockdown of cyclin D2, enhances HIV-1 replication in GM-CSF macrophages through inactivation of SAMHD1 restriction factor by phosphorylation. Co-immunoprecipitation experiments show that cyclin D2 forms a complex with CDK4 and p21, a factor known to restrict HIV-1 replication by affecting the function of the downstream cascade that leads to SAMHD1 deactivation. Thus, we demonstrate that cyclin D2 acts as regulator of cell cycle proteins affecting SAMHD1-mediated HIV-1 restriction in non-proliferating macrophage