BACKGROUND:Treatment with direct-acting antivirals (DAA) eradicates hepatitis C virus (HCV) from most chronic carriers. Information on regression of liver fibrosis and the influence of HIV is scarce ...in cured patients.
METHODS:All consecutive HCV-infected individuals treated with DAA at our institution were examined. Hepatic elastography was performed at baseline and at the time of SVR12. Liver fibrosis regression was defined as a shift from advanced fibrosis (Metavir F3-F4) to null–mild fibrosis (F0–F2) and/or a reduction greater than 30% kPa. AST to platelet ratio index (APRI) and fibrosis 4 (FIB-4) scores were calculated in parallel.
RESULTS:A total of 260 patients were treated with DAA. All but 14 achieved SVR12 and represented the study population. HIV confection was present in 42%. At baseline, 57.2% had advanced liver fibrosis with a median of 11 kPa, FIB-4 of 2.4, and APRI of 0.95. At the time of SVR12, a median reduction of 2.1 kPa (P < 0.001) was recognized using elastography. A significant fibrosis regression was seen in 40%, being more frequent in patients with baseline advanced fibrosis than in those with null–mild fibrosis (52.3 vs. 22.5%; P < 0.001). Even so, 41.2% of patients with baseline F3–F4 kept within cirrhotic scores. In multivariable analysis, only baseline stiffness was significantly associated with the extent of liver fibrosis regression.
CONCLUSION:HCV cure with DAA is associated with regression of liver fibrosis in most patients treated with DAA, as measured using elastography, FIB-4 and APRI. This benefit is more pronounced in patients with baseline advanced fibrosis and cirrhosis. The dynamics of liver fibrosis regression are not influenced by HIV coinfection.
An examination of the intersection of public discourses on sexualities with recent political, economic, and social shifts in the national context of Mexico and the Mexican diaspora in the United ...States.
The following study analyzes the creation, strengthening, and impact of the Spanish Catholic
Kings’ “Hermandad General” in the province of León (Spain) from 1477 to 1504, a time frame that
coincides ...with the reign of Isabel I of Castille. For that purpose, a preliminary bibliographical review
has been conducted and subsequently compared with the information provided by documentary
sources related to the abovementioned time and area. The majority of the data comes from the General
Archive of Simancas and, incidentally, from Archive of the Royal Chancellor of Valladolid.
El presente estudio versa sobre la Hermandad General de los Reyes Católicos y su consolidación, fundamento e impacto en la provincia de León, desde el año 1477 hasta 1504, coincidiendo con el reinado de Isabel I de Castilla. Para ello, se ha partido del análisis bibliográfico existente sobre la citada Hermandad General que, con posterioridad, ha sido comparado con las noticias que sobre la misma se encuentran incluidas en las fuentes documentales relativas al contexto espaciotemporal definido, procedentes fundamentalmente del Archivo General de Simancas y, de manera anecdótica, del Archivo de la Real Chancillería de Valladolid.
Mesenchymal stem cells (MSCs) are the subject of intense research as they are a potential therapeutic tool for several clinical applications. The new MSCs action models are focused on the use of ...MSC‐derived secretome which contains several growth factors, cytokines, microRNAs, and extracellular vesicles such as exosomes. Exosomes have recently emerged as a component with great potential involved as mediators in cellular communication. The isolation and identification of exosomes has made it possible for them to be used in cell‐free therapies. The purposes of this study are: (i) to detect exosomes released into adipose‐derived MSC conditioned cell culture medium, (ii) to identify exosome morphology, and (iii) to carry out a complete characterization of said exosomes. Moreover, it is aimed at determining which method for exosome isolation would be best to use. Precipitation has been identified as a highly useful method of exosome isolation since it provides higher efficiency and purity values than other methods. A broad characterization of the exosomes present in the MSC‐conditioned medium was also carried out. This work fills a gap in the existing literature on bioactive molecules which have attracted a great deal of interest due to their potential use in cellular therapies.
Isolation and characterization of exosomes from adipose tissue‐derived mesenchymal stem cells.
Objetivo/contexto: Este artículo busca explicar el éxito electoral de Iván Duque en las elecciones de 2018. La victoria del candidato uribista es paradójica por dos razones. Primero, Duque hizo ...campaña contra el proceso de paz, uno de los logros más importantes en la historia reciente colombiana y un paso importante para reducir la violencia y fortalecer la democracia del país. Segundo, Duque era el candidato más inexperto de la derecha. Logró derrotar a políticos más visibles, con más trayectoria y mejor acceso a maquinarias electorales. Metodología: El texto presenta un estudio de caso que triangula información de fuentes primarias y secundarias, encuestas de opinión pública, análisis de datos electorales y encuestas a parlamentarios. Conclusiones: La victoria de Iván Duque es el resultado de dos procesos simultáneos: la consolidación del uribismo -la facción “guerrerista” de la derecha- y el surgimiento del clivaje socioeconómico, históricamente subordinado a temas de seguridad pública. El primer proceso es consecuencia de las negociaciones con las FARC y la desinstitucionalización del sistema de partidos. Juntos, estos factores fortalecieron la maquinaria política del Centro Democrático y disminuyeron la capacidad de las élites tradicionales de movilizar votos. El segundo proceso es el resultado de la interacción entre los acuerdos con las FARC y la crisis humanitaria en Venezuela. El proceso de paz abrió espacios a la izquierda del espectro ideológico, de manera que Gustavo Petro aprovechó para entusiasmar a los votantes con propuestas socioeconómicas de izquierda. Su programa le permitió llegar a la segunda vuelta. Una vez ahí, la crisis en Venezuela jugó en su contra. Asustados de que Petro convirtiera a Colombia en una “segunda Venezuela” los votantes de centro y centro-derecha votaron por Duque. Originalidad: a pesar de su importancia, el uribismo ha sido poco estudiado desde una perspectiva comparada. Este artículo se suma a los esfuerzos por entender las similitudes y diferencias de esta corriente de la derecha en comparación con otras corrientes de derecha en otros países latinoamericanos. Este texto es también uno de los primeros artículos en analizar las elecciones de 2018 y sus consecuencias a corto y largo plazo.
Low-count monoclonal B-cell lymphocytosis is defined by the presence of very low numbers of circulating clonal B cells, usually phenotypically similar to chronic lymphocytic leukemia cells, whose ...biological and clinical significance remains elusive. Herein, we re-evaluated 65/91 low-count monoclonal B-cell lymphocytosis cases (54 chronic lymphocytic leukemia-like and 11 non-chronic lymphocytic leukemia-like) followed-up for a median of seven years, using high-sensitivity flow cytometry and interphase fluorescence
hybridization. Overall, the clone size significantly increased in 69% of low-count monoclonal B-cell lymphocytosis cases, but only one subject progressed to high-count monoclonal B-cell lymphocytosis. In parallel, the frequency of cytogenetic alterations increased over time (32%
61% of cases, respectively). The absolute number of the major T-cell and natural killer cell populations also increased, but only among chronic lymphocytic leukemia-like cases with increased clone size
age- and sex-matched controls. Although progression to chronic lymphocytic leukemia was not observed, the overall survival of low-count monoclonal B-cell lymphocytosis individuals was significantly reduced
non-monoclonal B-cell lymphocytosis controls (
=0.03) plus the general population from the same region (
≤0.001), particularly among females (
=0.01); infection and cancer were the main causes of death in low-count monoclonal B-cell lymphocytosis. In summary, despite the fact that mid-term progression from low-count monoclonal B-cell lymphocytosis to high-count monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia appears to be unlikely, these clones persist at increased numbers, usually carrying more genetic alterations, and might thus be a marker of an impaired immune system indirectly associated with a poorer outcome, particularly among females.
Oral DAA have demonstrated high efficacy as treatment of hepatitis C. However, the presence of resistance‐associated substitutions (RAS) at baseline has occasionally been associated with impaired ...treatment response. Herein, we examined the impact of baseline RAS at the HCV NS5A gene region on treatment response in a real‐life setting. All hepatitis C patients treated with DAA including NS5A inhibitors at our institution were retrospectively examined. The virus NS5A gene was analyzed using population sequencing at baseline and after 24 weeks of completing therapy in all patients that failed. All changes recorded at positions 28, 29, 30, 31, 32, 58, 62, 92, and 93 were considered. A total of 166 patients were analyzed. HCV genotypes were as follows: G1a (31.9%), G1b (48.2%), G3 (10.2%), and G4 (9.6%). Overall, 69 (41.6%) patients were coinfected with HIV and 46.7% had advanced liver fibrosis (Metavir F3‐F4). Sixty (36.1%) patients had at least one RAS at baseline, including M28A/G/T (5), Q30X (12), L31I/F/M/V (6), T58P/S (25), Q/E62D (1), A92 K (7), and Y93C/H (15). Overall, 4.8% had two or more RAS, being more frequent in G4 (12.5%) followed by G1b (6.3%) and G1a (1.9%). Of 10 (6%) patients that failed DAA therapy, five had baseline NS5A RAS. No association was found for specific baseline RAS, although changes at position 30 were more frequent in failures than cures (22.2% vs 6.4%, P = 0.074). Moreover, the presence of two or more RAS at baseline was more frequent in failures (HR: 7.2; P = 0.029). Upon failure, six patients showed emerging RAS, including Q30C/H/R (3), L31M (1), and Y93C/H (2). Baseline NS5A RAS are frequently seen in DAA‐naïve HCV patients. Two or more baseline NS5A RAS were found in nearly 5% and were significantly associated to DAA failure. Therefore, baseline NS5A testing should be considered when HCV treatment is planned with NS5A inhibitors.
During the Great Depression, hundreds of thousands of Mexican migrants and Mexican Americans left the United States for Mexico. Some hoped they could escape the economic crisis in the United States, ...while others were forced to leave their homes. For many who traveled via train as part of repatriation campaigns, they had no home or community in Mexico to return to or found themselves stranded in towns and cities along railway routes. In these regions in northern Mexico, resentment against returning migrants intensified as repatriates were increasingly viewed as economic and social disturbances.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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