Association between IL7RA polymorphisms and the successful therapy against HCV in HIV/HCV-coinfected patients.

Interleukin-7 (IL-7) is a critical factor in maintaining or inducing effective antiviral CD4+ and CD8+ T-cell responses. The aim of this study was to examine the association of interleukin-7 receptor-α (IL7RA) polymorphisms with a sustained virologic response (SVR) after hepatitis C virus (HCV) therapy with pegylated interferon-alpha plus ribavirin (pegIFNα/ribavirin) in 177 human immunodeficiency virus (HIV)/HCV-coinfected patients. We performed a retrospective study in 177 naïve patients who started HCV treatment. The IL7RA rs6897932, rs987106, and rs3194051 polymorphisms were genotyped by the GoldenGate® assay. An SVR was defined as undetectable HCV viral load through 24 weeks after the end of HCV treatment. The highest SVR rate was found in patients with the rs6897932 CC (p = 0.029) and rs3194051 GG (p = 0.002) genotypes, and HCV genotypes 2/3 (GT2/3) infected patients with the rs987106 AA genotype (p = 0.048). Additionally, carriers of the rs3194051 GG genotype had a higher likelihood of achieving an SVR [adjusted odds ratio (aOR) = 5.32; 95 % confidence interval (CI) = 1.07-26.94; p = 0.040] than patients with the rs3194051 AA/AG genotype, while rs6897932 CC (aOR = 0.63; p = 0.205) and rs987106 AA (aOR = 0.60; p = 0.213) were not significant. Moreover, three major haplotypes were found: 46.6 % for CTA, 32.4 % for CAG, and 20.7 % for TAA haplotypes. Patients infected with GT2/3 and carriers of the CTA haplotype had lower odds of achieving an SVR (aOR = 0.08; p = 0.004) and the CAG haplotype (favorable alleles) had higher odds of achieving an SVR than other haplotypes (aOR = 21.96; p < 0.001). IL7RA polymorphisms seem to play a significant role in the virological response to pegIFNα/ribavirin therapy in HIV/HCV-coinfected patients, in particular among patients infected with HCV GT2/3.

[Reproducibility and accuracy in the morphometric and mechanical quantification of trabecular bone from 3 Tesla magnetic resonance images]. / Reproducibilidad y exactitud en la cuantificación morfométrica y mecánica del hueso trabecular a partir de imágenes de resonancia magnética de Tesla.

OBJECTIVE: We used an animal model to analyze the reproducibility and accuracy of certain biomarkers of bone image quality in comparison to a gold standard of computed microtomography (µCT). MATERIAL AND METHODS: We used magnetic resonance (MR) imaging and µCT to study the metaphyses of 5 sheep tibiae. The MR images (3 Teslas) were acquired with a T1-weighted gradient echo sequence and an isotropic spatial resolution of 180µm. The µCT images were acquired using a scanner with a spatial resolution of 7.5µm isotropic voxels. In the preparation of the images, we applied equalization, interpolation, and thresholding algorithms. In the quantitative analysis, we calculated the percentage of bone volume (BV/TV), the trabecular thickness (Tb.Th), the trabecular separation (Tb.Sp), the trabecular index (Tb.N), the 2D fractal dimension (D(2D)), the 3D fractal dimension (D(3D)), and the elastic module in the three spatial directions (Ex, Ey and Ez). RESULTS: The morphometric and mechanical quantification of trabecular bone by MR was very reproducible, with percentages of variation below 9% for all the parameters. Its accuracy compared to the gold standard (µCT) was high, with errors less than 15% for BV/TV, D(2D), D(3D), and E(app)x, E(app)y and E(app)z. CONCLUSIONS: Our experimental results in animals confirm that the parameters of BV/TV, D(2D), D(3D), and E(app)x, E(app)y and E(app)z obtained by MR have excellent reproducibility and accuracy and can be used as imaging biomarkers for the quality of trabecular bone.

Etravirine-based highly active antiretroviral therapy in HIV-1-infected paediatric patients.

BACKGROUND: We evaluated the efficacy, safety and tolerability of etravirine in paediatric patients vertically infected with HIV-1. METHODS: A multicentre retrospective study of 23 multidrug-resistant paediatric patients (five children and 18 adolescents) enrolled in the study from 1 September 2007 to 28 February 2010 was carried out. We performed a longitudinal analysis of immunological, virological and clinical data. RESULTS: The median age of the patients was 14.2 years [interquartile range (IQR) 12.5-15.8 years]. At baseline, the median HIV-1 RNA was 29 000 (4.5 log(10) ) HIV-1 RNA copies/mL (range 4300-83 000 copies/mL), the median CD4 T-cell count was 445 cells/µL (range 221-655 cells/µL) and the median CD4 percentage was 19.6% (IQR 13.0-31.0). Remarkably, 16 of 23 patients (70%) harboured one or more etravirine-associated resistance mutations. The backbone regimen included at least two fully active drugs in 91% of patients. After etravirine-based therapy, 20 patients (87%) achieved HIV-1 RNA<400 copies/mL and 18 of 23 (78%) achieved HIV-1 RNA<50 copies/mL: three (13%) within the first month, seven (30%) within the first 4 months, and six (26%) between the 5th and 8th months. CD4 T-cell recovery was observed in 19 patients (83%). The median follow-up time was 48.4 weeks (IQR 35.7-63.4 weeks); four patients (17%) were exposed to etravirine for >120 weeks. Three mild/short-term and two moderate skin rashes were observed in the adolescents. Laboratory abnormalities included hypercholesterolaemia (11 of 23 patients), hypertriglyceridaemia (eight of 23 patients), and reduced high-density lipoprotein cholesterol (10 of 23 patients). Adherence was complete in seven patients (30%). No patients showed complete resistance to etravirine after follow-up. However, three of 21 patients (14%) who initially showed intermediate resistance interrupted etravirine treatment because of virological failure. CONCLUSIONS: We observed a sustained antiviral response and improved immunological parameters in multidrug-resistant paediatric patients, most of whom had received etravirine as part of salvage regimens with at least two fully active drugs.

Quantitative structural analysis of trabecular alveolar bone in the mandible by multidetector computed tomography: differences according to tooth presence and type. / Análisis estructural cuantitativo del hueso alveolar trabecular de la mandíbula en tomografía computarizada multidetector: diferencias por tipo y estado dentario.

BACKGROUND AND OBJECTIVE: There is a lack of quantitative measures of the quality of alveolar trabecular bone, an important factor in implantology. This study aimed to develop a method of objectively assessing the quality of trabecular bone by means of image processing and structural analysis of multidetector computed tomography images and to establish differences between tooth types and tooth presence/absence. MATERIALS AND METHODS: We analyzed 20 patients who underwent multidetector computed tomography to evaluate mandibular bone and tooth positioning. Image analysis included automatic segmentation of the mandible, obtainment of sections perpendicular to the dental arch, and structural analysis of the trabecular bone in each section. We calculated the ratio between the volume of bone and the total volume of the section, the thickness, the trabecular number, and the mean attenuation in Hounsfield units. We analyzed the differences among different tooth types (incisors, canines, premolars, and molars) and between present and absent teeth. RESULTS: We found statistically significant differences between different tooth types and between sections in which teeth were present or absent. Incisors had a greater ratio of trabecular bone; the ratio of trabecular bone progressively decreased from the incisors to the canines, premolars, and molars. The ratio of trabecular bone was greater in sections in which teeth were absent than in those in which teeth were present. CONCLUSIONS: The method allows to quantify the structural properties of alveolar bone from multidetector computed tomography images. Our results provide an objective picture of the bone substrate that can be useful for planning and following up dental implant procedures.

Validation of a generation 4 phosphorus-containing polycationic dendrimer for gene delivery against HIV-1.

Gene therapy, in which oligomeric genetic material is carried into cells by nano-sized gene delivery vehicles to interfere with gene expression, represents a promising approach for preventive therapy against HIV/AIDS pandemic. Herein, we evaluate the usefulness of a phosphorus-containing dendrimer G4(NH+Et2Cl-)96 as a delivery agent of ODNs and siRNAs. G4(NH+Et2Cl-)96 formed stable complexes with ODNs or siRNAs and exhibited very low cytotoxicity in Sup T1 cells or PBMC. Functional validation was performed by using specific siRNA against HIV-1 Nef, siNEF to interfere in HIV-1 replication. G4(NH+Et2Cl-)96/siNEF dendriplex showed a high efficiency in Nef silencing. Furthermore, in vitro treatment of HIV-infected PBMC with G4(NH+Et2Cl-)96/siNEF dendriplex significantly reduced the viral replication. Our results prove the usefulness of phosphorus-containing dendrimers to deliver and transfect siRNA into CD4-T cells as a potential alternative therapy in the HIV-1 infection.

Short communication: evaluation of the effect of enfuvirtide in 11 HIV-1 vertically infected pediatric patients outside clinical trials.

The effect of enfuvirtide (ENF) in 11 HIV-1 heavily antiretroviral-experienced children and adolescents enrolled in the HIV-1 Paediatric Spanish cohort was further investigated. Patients who received ENF with novel drugs (etravirine, darunavir, and/or tipranavir) reached and maintained undetectable plasma HIV-1 RNA levels and showed immunological recovery within the first 3 months of therapy that was maintained during the follow-up. Viremia was not fully suppressed in patients who did not combine ENF with novel drugs but interestingly, immunological benefit was observed in half of these patients. Therefore, ENF showed a greater and more stable efficacy when administrated with novel drugs.

Análisis estructural cuantitativo del hueso alveolar trabecular de la mandíbula en tomografía computarizada multidetector: diferencias por tipo y estado dentario / Quantitative structural analysis of trabecular alveolar bone in the mandible by multidetector computed tomography: differences according to tooth presence and type

Antecedentes y objetivo: Existe una carencia de métricas cuantitativas de la calidad del hueso trabecular alveolar, factor determinante en implantología. El objetivo de este estudio es desarrollar una metodología con tomografía computarizada multidetector para objetivar la calidad del hueso trabecular y establecer diferencias entre los distintos tipos y el estado de las piezas dentarias mediante procesado de imágenes y análisis estructural. Materiales y métodos: Se analizan 20 pacientes con exploración de tomografía computarizada multidetector dental para la valoración del hueso mandibular y posiciones dentales. El análisis de las imágenes incluyó la segmentación automática de la mandíbula, obtención de secciones perpendiculares a la arcada dentaria y análisis estructural del hueso trabecular de cada sección. Se obtuvieron la ratio entre volumen de hueso y volumen total de la sección, el grosor, la separación y el número trabecular, y la atenuación promedio en unidades Hounsfield. Se analizaron diferencias entre tipos de diente (incisivos, caninos, premolares y molares) y entre estados de las piezas dentarias (ausente o presente). Resultados: Se obtuvieron diferencias estadísticamente significativas entre los tipos y estados de las piezas. Por tipo, los incisivos mostraron mayor ratio de hueso trabecular, con disminución progresiva para caninos, premolares y molares. Por estado, las secciones pertenecientes a dientes ausentes presentaron mayor ratio de hueso que con el diente presente. Conclusiones: La metodología desarrollada permite cuantificar las propiedades estructurales del hueso alveolar a partir de imágenes de tomografía computarizada multidetector. Los resultados obtenidos objetivan el estado del sustrato óseo de cara a la planificación y seguimiento de la colocación de implantes dentales

Background and objective: There is a lack of quantitative measures of the quality of alveolar trabecular bone, an important factor in implantology. This study aimed to develop a method of objectively assessing the quality of trabecular bone by means of image processing and structural analysis of multidetector computed tomography images and to establish differences between tooth types and tooth presence/absence. Materials and methods: We analyzed 20 patients who underwent multidetector computed tomography to evaluate mandibular bone and tooth positioning. Image analysis included automatic segmentation of the mandible, obtainment of sections perpendicular to the dental arch, and structural analysis of the trabecular bone in each section. We calculated the ratio between the volume of bone and the total volume of the section, the thickness, the trabecular number, and the mean attenuation in Hounsfield units. We analyzed the differences among different tooth types (incisors, canines, premolars, and molars) and between present and absent teeth. Results: We found statistically significant differences between different tooth types and between sections in which teeth were present or absent. Incisors had a greater ratio of trabecular bone; the ratio of trabecular bone progressively decreased from the incisors to the canines, premolars, and molars. The ratio of trabecular bone was greater in sections in which teeth were absent than in those in which teeth were present. Conclusions: The method allows to quantify the structural properties of alveolar bone from multidetector computed tomography images. Our results provide an objective picture of the bone substrate that can be useful for planning and following up dental implant procedures

Reproducibilidad y exactitud en la cuantificación morfométrica y mecánica del hueso trabecular a partir de imágenes de resonancia magnética de Tesla / Reproducibility and accuracy in the morphometric and mechanical quantification of trabecular bone from 3 Tesla magnetic resonance images

Objetivo. En este trabajo se analizan en un modelo animal la reproducibilidad y la exactitud de ciertos biomarcadores de imagen de calidad ósea utilizando como patrón de referencia la microtomografía computarizada (mTC). Material y métodos. Se estudiaron con RM y mTC 5 metáfisis tibiales de oveja. Las imágenes de RM (3 Tesla) se adquirieron con una secuencia eco de gradiente potenciada en T1 y una resolución espacial isotrópica de 180 mm. Las imágenes de mTC se adquirieron en un escáner con una resolución espacial de 7,5 mm en vóxeles isotrópicos. En la preparación de las imágenes se aplicaron algoritmos de ecualización, interpolación y umbralización. En el análisis cuantitativo se calculó el porcentaje de volumen de hueso (BV/TV), el grosor trabecular (Tb.Th), la separación trabecular (Tb.Sp), el índice trabecular (Tb.N), la dimensión fractal en 2 D (D2D) y 3 D (D3D) y el módulo elástico en las 3 direcciones del espacio (Ex, Ey y Ez). Resultados. La cuantificación morfométrica y mecánica del hueso esponjoso con la RM fue muy reproducible, con porcentajes de variación por debajo del 9% para todos los parámetros. Su exactitud con respecto a la mTC fue alta, con errores inferiores al 15% para BV/TV, D2D, D3D y Eappx, Eappy y Eappz. Conclusiones. Los resultados experimentales en animales confirman que los parámetros de BV/TV, D2D, D3D y Eappx, Eappy y Eappz obtenidos a partir de RM tienen una excelente reproducibilidad y precisión, y pueden emplearse como biomarcadores de imagen de la calidad del hueso trabecular (AU)

Objective: We used an animal model to analyze the reproducibility and accuracy of certain biomarkers of bone image quality in comparison to a gold standard of computed microtomography (mCT). Material and methods: We used magnetic resonance (MR) imaging and mCT to study the metaphyses of 5 sheep tibiae. The MR images (3 Teslas) were acquired with a T1-weighted gradient echo sequence and an isotropic spatial resolution of 180 mm. The mCT images were acquired using a scanner with a spatial resolution of 7.5 mm isotropic voxels. In the preparation of the images, we applied equalization, interpolation, and thresholding algorithms. In the quantitative analysis, we calculated the percentage of bone volume (BV/TV), the trabecular thickness (Tb.Th), the trabecular separation (Tb.Sp), the trabecular index (Tb.N), the 2 D fractal dimension (D2D), the 3 D fractal dimension (D3D), and the elastic module in the three spatial directions (Ex, Ey and Ez). Results: The morphometric and mechanical quantification of trabecular bone by MR was very reproducible, with percentages of variation below 9% for all the parameters. Its accuracy compared to the gold standard (mCT) was high, with errors less than 15% for BV/TV, D2D, D3D, and Eappx, Eappy and Eappz. Conclusions: Our experimental results in animals confirm that the parameters of BV/TV, D2D, D3D, and Eappx, Eappy and Eappz obtained by MR have excellent reproducibility and accuracy and can be used as imaging biomarkers for the quality of trabecular bone (AU)