Prevalence and Trends in Transmitted and Acquired Antiretroviral Drug Resistance, Washington, DC, 1999-2014.

Background Drug resistance limits options for antiretroviral therapy (ART) and results in poorer health outcomes among HIV-infected persons. We sought to characterize resistance patterns and to identify predictors of resistance in Washington, DC. Methods We analyzed resistance in the DC Cohort, a longitudinal study of HIV-infected persons in care in Washington, DC. We measured cumulative drug resistance (CDR) among participants with any genotype between 1999 and 2014 (n = 3411), transmitted drug resistance (TDR) in ART-naïve persons (n = 1503), and acquired drug resistance (ADR) in persons with genotypes before and after ART initiation (n = 309). Using logistic regression, we assessed associations between patient characteristics and transmitted resistance to any antiretroviral. Results Prevalence of TDR was 20.5%, of ADR 40.5%, and of CDR 45.1% in the respective analysis groups. From 2004 to 2013, TDR prevalence decreased for nucleoside and nucleotide analogue reverse transcriptase inhibitors (15.0 to 5.5%; p = 0.0003) and increased for integrase strand transfer inhibitors (INSTIs) (0.0–1.4%; p = 0.04). In multivariable analysis, TDR was not associated with age, race/ethnicity, HIV risk group, or years from HIV diagnosis. Conclusions In this urban cohort of HIV-infected persons, almost half of participants tested had evidence of CDR; and resistance to INSTIs was increasing. If this trend continues, inclusion of the integrase-encoding region in baseline genotype testing should be strongly considered

Puces à cellules et génomique fonctionnelle

À l’interface du vivant et de l’inerte, se développe un ensemble de nouvelles technologies regroupées sous le terme générique de biopuces. Grâce à la miniaturisation, nous pouvons imaginer que, demain, de nombreuses études biologiques et médicales se feront avec des biopuces qui permettront d’accroître de plusieurs ordres de grandeur le parallélisme des analyses, les vitesses de réaction des tests et leur débit, tout en réduisant les coûts. Cette évolution a démarré avec l’apparition des puces à ADN et se poursuit aujourd’hui avec, entre autres, les puces à cellules qui permettent d’accélérer considérablement l’étude des gènes de fonctions inconnues et leurs implications potentielles dans différentes maladies. Bien que la technologie en soit encore à ses prémices, il est vraisemblable que les puces à cellules feront évoluer la biologie et la médecine de manière significative.With the complete sequencing of the human genome, research priorities have shifted from the identification of genes to the elucidation of their function. Methods currently used by scientists to characterize gene function, such as knock-out mice, are based upon loss of protein function and analysis of the resulting phenotypes to infer a potential role for the protein under scrutiny. Until now, these methods have been successful but time consuming and only a few genes at a time could be analyzed. Cell microarrays allow to simultaneously transfect thousands of different nucleic acid molecules, RNA or DNA, into adherent cells. It is then possible to analyze a large pallet of resulting phenotypes in clusters of transfected cells. We are currently manufacturing cell microarrays with collections of full-length cDNA cloned in expression vectors (gain of function analyses) or siRNA (loss of function studies) to unravel function of genes involved in differentiation and proliferation of human cells. Although there are still some technological difficulties to overcome, the potential for cell microarrays to speed up functional exploration of genomes is very promising

Evaluación para el aprendizaje en enseñanza presencial y virtual de emergencia en la universidad: satisfacción y frustración de las Necesidades Psicológicas Básicas del estudiantado

The satisfaction and frustration of basic psychological needs (BPN) in Assessment for Learning (AfL)-based interventions in the context of Physical Education Teacher Education is a research area that has not received much attention. This study measures students’ BPN in two consecutive cohorts (face-to-face and emergency virtual teaching) during a module at university that uses AfL in an autonomy supportive learning environment. The Satisfaction and Frustration of the Basic Psychological Needs Scale for Training was administered to fourth year students. Qualitative open-ended questions were incorporated into the questionnaire to deepen on students’ opinions on the experience. The results showed high levels of BPN satisfaction plus low levels of frustration in both face-toface and virtual teaching. Likewise, students confirmed the importance of autonomy, structure and feedback in virtual classes, which supports the idea that autonomy and structure are complementary and not contradictory. It also shows how technologies in virtual teaching generated commitment and learning, favoring continual feedback on tutored work. Although this study contributes to scaling up the empirical evidence of the effects of AfL on motivation, a lot of terrain remains to be explored on its implementation in university contexts that support BPN. La satisfacción y frustración de las necesidades psicológicas básicas (NPB) en intervenciones que utilizan la Evaluación para el Aprendizaje (EpA) en el contexto de la Formación Inicial del Profesorado de Educación Física, es un área de investigación que no ha recibido mucha atención. Este estudio analiza las NPB del estudiantado en dos cohortes consecutivas (presencial y enseñanza virtual de emergencia) en una asignatura que utiliza la EpA en un entorno de apoyo a la autonomía. La Escala de Satisfacción y Frustración de las Necesidades Psicológicas Básicas para la Formación se administró al alumnado de cuarto curso del Grado de Ciencias de la Actividad Física y Deportes. Se incorporaron al cuestionario preguntas cualitativas abiertas para conocer la opinión del estudiantado sobre la experiencia. Los resultados mostraron un alto nivel de satisfacción con baja frustración de las necesidades tanto en la docencia presencial como virtual. Asimismo, se confirmó la importancia que el estudiantado da a la autonomía, la estructura y la retroalimentación en las clases virtuales, lo que sustenta la idea de que la autonomía y la estructura se complementan y no son contradictorias. También muestra cómo las tecnologías en la enseñanza virtual generaron compromiso y aprendizaje facilitando la retroalimentación continua del trabajo tutorado. Aunque este estudio contribuye a ampliar la evidencia empírica de los efectos de la EpA en la motivación, queda mucho terreno por explorar sobre su implementación en contextos universitarios que apoyen las NPB.Actividad Física y Deport

Two independent epigenetic biomarkers predict survival in neuroblastoma

Background: Neuroblastoma (NB) is the most common extracranial pediatric solid tumor with a highly variable clinical course, ranging from spontaneous regression to life-threatening disease. Survival rates for high-risk NB patients remain disappointingly low despite multimodal treatment. Thus, there is an urgent clinical need for additional biomarkers to improve risk stratification, treatment management, and survival rates in children with aggressive NB. Results: Using gene promoter methylation analysis in 48 neuroblastoma tumors with microarray technology, we found a strong association between survival and gene promoter hypermethylation (P = 0.036). Hypermethylation of 70 genes significantly differentiated high-risk survivor patients from those who died during follow-up time. Sixteen genes with relevant roles in cancer biology were further validated in an additional cohort of 83 neuroblastoma tumors by bisulfite pyrosequencing. High promoter methylation rates of these genes were found in patients with metastatic tumors (either stage metastatic (M) or metastatic special (MS)), 18 months or older at first diagnosis, MYCN amplification, relapsed, and dead. Notably, the degree of methylation of retinoblastoma 1 (RB1) and teratocarcinoma-derived growth factor 1 (TDGF1) predicts event-free and overall survival independently of the established risk factors. In addition, low RB1 mRNA expression levels associate with poor prognosis suggesting that promoter methylation could contribute to the transcriptional silencing of this gene in NB. Conclusions: We found a new epigenetic signature predictive for NB patients' outcome: the methylation status of RB1 and TDGF1 associate with poorer survival. This information is useful to assess prognosis and improve treatment selection

Transgressive segregation reveals mechanisms of Arabidopsis immunity to Brassica-infecting races of white rust (Albugo candida)

Arabidopsis thaliana accessions are universally resistant at the adult leaf stage to white rust (Albugo candida) races that infect the crop species Brassica juncea and Brassica oleracea. We used transgressive segregation in recombinant inbred lines to test if this apparent species-wide (nonhost) resistance in A. thaliana is due to natural pyramiding of multiple Resistance (R) genes. We screened 593 inbred lines from an Arabidopsis multiparent advanced generation intercross (MAGIC) mapping population, derived from 19 resistant parental accessions, and identified two transgressive segregants that are susceptible to the pathogen. These were crossed to each MAGIC parent, and analysis of resulting F 2 progeny followed by positional cloning showed that resistance to an isolate of A. candida race 2 (Ac2V) can be explained in each accession by at least one of four genes encoding nucleotide-binding, leucine-rich repeat (NLR) immune receptors. An additional gene was identified that confers resistance to an isolate of A. candida race 9 (AcBoT) that infects B. oleracea. Thus, effector-triggered immunity conferred by distinct NLR-encoding genes in multiple A. thaliana accessions provides species-wide resistance to these crop pathogens

Estudio plurianual del efecto del régimen hídrico sobre la composición nitrogenada de las variedades blancas Cigüente, Macabeo, Moscatel de Alejandría y Verdejo, cultivadas en diversas regiones de España

Este trabajo analiza el efecto del régimen hídrico y del año sobre el perfil aminoacídico y el amonio de diferentes variedades blancas, conducidas en espaldera, en diferentes zonas vitícolas españolas. Las variedades, la localización y los tratamientos aplicados fueron: Cigüente (Ci) en Badajoz, secano y riego al 100% de ETc; Macabeo (Ma) en Albacete, 25% y 33% aprox de ETc; Moscatel de Alejandría (Mo) en Valencia, 50% y 100% de ETc; y Verdejo (Ve) en Valladolid, secano y 100% aprox. de ETc. En vendimia se analizó la composición aminoacídica y el amonio de la uva mediante HPLC y se calcularon el CTA (Contenido Amínico Total, mgL-1), aminoácidos asimilables (AA, mgL-1) y el YAN (Nitrógeno Fácilmente Asimilable por las levaduras). En Ci, Ma y Ve se hallaron diferencias significativas entre tratamientos para la mayoría de los aminoácidos. Debido a la variabilidad climática interanual observada, en la mayoría de ellos se encontró interacción significativa tratamiento*año, especialmente en Ci y Ma. La variación interanual y el efecto del riego fueron de poca amplitud y significación en Mo, observándose descensos en los valores medios de los aminoácidos individuales y de CTA y YAN en la uva de los tratamientos más regados. En Ma la aplicación de mayor dosis de agua durante el preenvero provocó aumentos en la mayoría de los aminoácidos, de mayor amplitud en 2014. En Ci la tendencia, amplitud y significación del efecto tratamiento dependió incluso de la campaña analizada para un determinado aminoácido. El riego en Ve disminuyó la concentración de los aminoácidos presentes en las bayas. Aunque no se ha logrado establecer un grupo de aminoácidos común para todas las variedades que pudieran servir de indicadores del estado hídrico de la cepa, los resultados hallados en Ci y Ve sugieren la existencia de patrones comunes para determinados grupos de variedades cuando los estados hídricos son similares

Intracoronary Injection of In Situ Forming Alginate Hydrogel Reverses Left Ventricular Remodeling After Myocardial Infarction in Swine

ObjectivesThis study sought to determine whether alginate biomaterial can be delivered effectively into the infarcted myocardium by intracoronary injection to prevent left ventricular (LV) remodeling early after myocardial infarction (MI).BackgroundAlthough injectable biomaterials can improve infarct healing and repair, the feasibility and effectiveness of intracoronary injection have not been studied.MethodsWe prepared a calcium cross-linked alginate solution that undergoes liquid to gel phase transition after deposition in infarcted myocardium. Anterior MI was induced in swine by transient balloon occlusion of left anterior descending coronary artery. At 4 days after MI, either alginate solution (2 or 4 ml) or saline was injected selectively into the infarct-related coronary artery. An additional group (n = 19) was treated with incremental volumes of biomaterial (1, 2, and 4 ml) or 2 ml saline and underwent serial echocardiography studies.ResultsExamination of hearts harvested after injection showed that the alginate crossed the infarcted leaky vessels and was deposited as hydrogel in the infarcted tissue. At 60 days, control swine experienced an increase in left ventricular (LV) diastolic area by 44%, LV systolic area by 45%, and LV mass by 35%. In contrast, intracoronary injection of alginate (2 and 4 ml) prevented and even reversed LV enlargement (p < 0.01). Post-mortem analysis showed that the biomaterial (2 ml) increased scar thickness by 53% compared with control (2.9 ± 0.1 mm vs. 1.9 ± 0.3 mm; p < 0.01) and was replaced by myofibroblasts and collagen.ConclusionsIntracoronary injection of alginate biomaterial is feasible, safe, and effective. Our findings suggest a new percutaneous intervention to improve infarct repair and prevent adverse remodeling after reperfused MI