An international consensus definition for contextual factors: findings from a nominal group technique

Objective: Emerging literature suggests contextual factors are important components of therapeutic encounters and may substantially influence clinical outcomes of a treatment intervention. At present, a single consensus definition of contextual factors, which is universal across all health-related conditions is lacking. The objective of this study was to create a consensus definition of contextual factors to better refine this concept for clinicians and researchers. Design: The study used a multi-stage virtual Nominal Group Technique (vNGT) to create and rank contextual factor definitions. Nominal group techniques are a form of consensus-based research, and are beneficial for identifying problems, exploring solutions and establishing priorities. Setting: International. Main outcome measures: The initial stages of the vNGT resulted in the creation of 14 independent contextual factor definitions. After a prolonged discussion period, the initial definitions were heavily modified, and 12 final definitions were rank ordered by the vNGT participants from first to last. Participants: The 10 international vNGT participants had a variety of clinical backgrounds and research specializations and were all specialists in contextual factors research. Results: A sixth round was used to identify a final consensus, which reflected the complexity of contextual factors and included three primary domains: (1) an overall definition; (2) qualifiers that serve as examples of the key areas of the definition; and (3) how contextual factors may influence clinical outcomes. Conclusion: Our consensus definition of contextual factors seeks to improve the understanding and communication between clinicians and researchers. These are especially important in recognizing their potential role in moderating and/or mediating clinical outcomes

Epidemiología lesional del balonmano de elite: estudio retrospectivo en equipos profesional y formativo de un mismo club

Objetivo Evaluar la incidencia y el patrón lesional en el balonmano de elite. Método Estudio retrospectivo y transversal de 496 jugadores, de 29 equipos (divididos por categorías según edad y nivel), durante 5 temporadas (2007-2012), de un club del sur de Europa. El equipo médico evaluó las lesiones y el tiempo de exposición por equipos. Se siguieron los criterios epidemiológicos según consenso UEFA y codificación OSICS-10. Resultados Se registraron 557 lesiones con 117.723 h de exposición totales. La incidencia lesional media de los equipos fue: 4,9 lesiones/1.000 h de exposición. Para el equipo Senior A (Profesional) fue de 4,3 (DE 1,8); Senior B, 3,4 (DE 1,6); Juvenil, 5,6 (DE 1,4); Cadete A, 5,5 (DE 2,5); Cadete B, 5,7 (DE 3,2), e Infantil, 4,9 (DE 1,9). No hubo diferencias estadísticamente significativas entre ellos, aunque los seniors tuvieron la mayor cantidad de horas de exposición (p < 0,001). Las localizaciones más frecuentes fueron tobillo (18,1%), rodilla (15,3%), muslo (12,9%) y región lumbar (10,6%). Las estructuras afectadas con más frecuencia fueron la lesión ligamentosa (27,3%) y la lesión «muscular por mecanismo indirecto» (20,5%). Esta última más en el Senior A, y la lesión ligamentosa en las categorías inferiores, aunque no se registraron diferencias significativas entre categorías. Conclusión El patrón y la incidencia lesional en el balonmano de elite es uniforme entre los equipos de diferentes categorías, con pequeñas diferencias que deberán tenerse en cuenta para optimizar los programas de prevención en cada categoría del balonmano formativo de elite

Estudio prospectivo de maduración, desarrollo e incidencia lesional en balonmano formativo de élite. ¿Puede el estado madurativo ser un factor determinante de la incidencia lesional en balonmano?

El objetivo de este estudio es describir la relación entre incidencia lesional (IL) y estado madurativo de jugadores varones de balonmano formativo (BmF) de alto nivel competicional. Se analizan durante 2 temporadas la incidencia de lesión deportiva de forma prospectiva en 133 jugadores, los criterios de maduración biológica y la carga física de exposición. Se siguieron los criterios para estudios de epidemiología lesional según el consenso UEFA. Las variables utilizadas para analizar el estado madurativo son los estadios de Tanner, la pubertad, el pico de velocidad de crecimiento, el volumen testicular y la edad ósea. Se registraron 190 lesiones para un total de 34.222 h de exposición. La IL total media de todas las categorías fue de 5,6 lesiones/1.000 h de exposición. En competición, el valor fue de 21,8 lesiones/1.000 h, y en entrenamiento, de 3,1 lesiones/1.000 h. No se encontraron diferencias estadísticamente significativas entre IL, la edad cronológica y los diferentes estados madurativos por ANOVA. El análisis estadístico multivariante registra cierta tendencia entre las asociaciones de IL en competición para categoría (p = 0,07), y en la IL en entrenamientos para Tanner (p = 0,091) y pubertad (p = 0,021). En conclusión, si bien no se detectaron diferencias significativas en la IL por edades en jugadores de BmF, sí se aprecia una tendencia real en determinados estadios madurativos mediante el análisis multivariante. Esto deberá tenerse en cuenta para planificación entrenamientos y estrategias de prevención de la lesión deportiva en el contexto del BmF

Estudi prospectiu de maduració, desenvolupament i incidència lesional en l’handbol formatiu d’elit. L’estadi maduratiu pot ser un factor determinant d’incidència lesional a l’handbol?

L’objectiu d’aquest estudi és descriure la relació entre incidència lesional (IL) i estat maduratiu de jugadors homes d’handbol formatiu (HbF) d’alt nivell competitiu. Durant 2 temporades s’analitza la incidència de la lesió esportiva de forma prospectiva, els criteris de maduració biològica i la càrrega física d’exposició, de 133 jugadors. Se seguiren els criteris del consens UEFA sobre estudis d’epidemiologia lesional. Les variables utilitzades per analitzar l’estat maduratiu foren els estadis de Tanner, la pubertat, el pic de velocitat de creixement, el volum testicular i l’edat òssia. Es registraren 190 lesions en un total de 34.222 h d’exposició. La IL total mitjana de totes las categories fou de 5,6 lesions/1.000 h d’exposició. Durant la competició, el valor fou de 21,8 lesions/1.000 h, i en l’entrenament de 3,1 lesions/1.000 h. No es trobaren diferències estadísticament significatives entre IL, edat cronològica i els diferents estadis maduratius en l’ANOVA. L’anàlisi estadística multivariant registrà una certa tendència a associar la IL en la categoria competició (p = 0,07), i la IL en entrenament en Tanner (p = 0,091) i pubertat (p = 0,021). En conclusió, tot i que no es detectaren diferències significatives en la IL per edat en jugadors d’HbF, s’aprecia una tendència real en determinats estadis maduratius mitjançant l’anàlisi multivariant, cosa que caldria que es tingués en compte per planificar entrenaments i estratègies de prevenció de lesions esportives en el context de l’HbF

Quaternary structure of a G-protein coupled receptor heterotetramer in complex with Gi and Gs

Background: G-protein-coupled receptors (GPCRs), in the form of monomers or homodimers that bind heterotrimeric G proteins, are fundamental in the transfer of extracellular stimuli to intracellular signaling pathways. Different GPCRs may also interact to form heteromers that are novel signaling units. Despite the exponential growth in the number of solved GPCR crystal structures, the structural properties of heteromers remain unknown. Results: We used single-particle tracking experiments in cells expressing functional adenosine A1-A2A receptors fused to fluorescent proteins to show the loss of Brownian movement of the A1 receptor in the presence of the A2A receptor, and a preponderance of cell surface 2:2 receptor heteromers (dimer of dimers). Using computer modeling, aided by bioluminescence resonance energy transfer assays to monitor receptor homomerization and heteromerization and G-protein coupling, we predict the interacting interfaces and propose a quaternary structure of the GPCR tetramer in complex with two G proteins. Conclusions: The combination of results points to a molecular architecture formed by a rhombus-shaped heterotetramer, which is bound to two different interacting heterotrimeric G proteins (Gi and Gs). These novel results constitute an important advance in understanding the molecular intricacies involved in GPCR function

A randomised controlled trial of a brief online mindfulness-based intervention on paranoia in a non-clinical sample

Paranoia is common and distressing in the general population and can impact on health, emotional well-being and social functioning, such that effective interventions are needed. Brief online mindfulness-based interventions (MBIs) have been shown to reduce symptoms of anxiety and depression in non-clinical samples, however at present there is no research investigating whether they can reduce paranoia. The current study explored whether a brief online MBI increased levels of mindfulness and reduced levels of paranoia in a non-clinical population. The mediating effect of mindfulness on any changes in paranoia was also investigated. One hundred and ten participants were randomly allocated to either a two week online MBI including 10 minutes of daily guided mindfulness practice or to a waitlist control condition. Measures of mindfulness and paranoia were administered at baseline, post-intervention and one-week follow-up. Participants in the MBI group displayed significantly greater reductions in paranoia compared to the waitlist control group. Mediation analysis demonstrated that change in mindfulness skills (specifically the observe, describe and nonreact facets of the FFMQ) mediated the relationship between intervention type and change in levels of paranoia. This study provides evidence that a brief online MBI can significantly reduce levels of paranoia in a non-clinical population. Furthermore, increases in mindfulness skills from this brief online MBI can mediate reductions in non-clinical paranoia. The limitations of the study are discussed

Single-molecule imaging reveals receptor-G protein interactions at cell surface hot spots

G-protein-coupled receptors mediate the biological effects of many hormones and neurotransmitters and are important pharmacological targets. They transmit their signals to the cell interior by interacting with G proteins. However, it is unclear how receptors and G proteins meet, interact and couple. Here we analyse the concerted motion of G-protein-coupled receptors and G proteins on the plasma membrane and provide a quantitative model that reveals the key factors that underlie the high spatiotemporal complexity of their interactions. Using two-colour, single-molecule imaging we visualize interactions between individual receptors and G proteins at the surface of living cells. Under basal conditions, receptors and G proteins form activity-dependent complexes that last for around one second. Agonists specifically regulate the kinetics of receptor-G protein interactions, mainly by increasing their association rate. We find hot spots on the plasma membrane, at least partially defined by the cytoskeleton and clathrin-coated pits, in which receptors and G proteins are confined and preferentially couple. Imaging with the nanobody Nb37 suggests that signalling by G-protein-coupled receptors occurs preferentially at these hot spots. These findings shed new light on the dynamic interactions that control G-protein-coupled receptor signalling

The role of kinetic context in apparent biased agonism at GPCRs

Biased agonism describes the ability of ligands to stabilize different conformations of a GPCR linked to distinct functional outcomes and offers the prospect of designing pathway-specific drugs that avoid on-target side effects. This mechanism is usually inferred from pharmacological data with the assumption that the confounding influences of observational (that is, assay dependent) and system (that is, cell background dependent) bias are excluded by experimental design and analysis. Here we reveal that ‘kinetic context’, as determined by ligand-binding kinetics and the temporal pattern of receptor-signalling processes, can have a profound influence on the apparent bias of a series of agonists for the dopamine D2 receptor and can even lead to reversals in the direction of bias. We propose that kinetic context must be acknowledged in the design and interpretation of studies of biased agonism