Computer-Controlled Biaxial Bioreactor for Investigating Cell-Mediated Homeostasis in Tissue Equivalents.

Soft biological tissues consist of cells and extracellular matrix (ECM), a network of diverse proteins, glycoproteins, and glycosaminoglycans that surround the cells. The cells actively sense the surrounding ECM and regulate its mechanical state. Cell-seeded collagen or fibrin gels, so-called tissue equivalents, are simple but powerful model systems to study this phenomenon. Nevertheless, few quantitative studies document the stresses that cells establish and maintain in such gels; moreover, most prior data were collected via uniaxial experiments whereas soft tissues are mainly subject to multiaxial loading in vivo. To begin to close this gap between existing experimental data and in vivo conditions, we describe here a computer-controlled bioreactor that enables accurate measurements of the evolution of mechanical tension and deformation of tissue equivalents under well-controlled biaxial loads. This device allows diverse studies, including how cells establish a homeostatic state of biaxial stress and if they maintain it in response to mechanical perturbations. It similarly allows, for example, studies of the impact of cell and matrix density, exogenous growth factors and cytokines, and different types of loading conditions (uniaxial, strip-biaxial, and biaxial) on these processes. As illustrative results, we show that NIH/3T3 fibroblasts establish a homeostatic mechanical state that depends on cell density and collagen concentration. Following perturbations from this homeostatic state, the cells were able to recover biaxial loading similar to homeostatic. Depending on the precise loads, however, they were not always able to fully maintain that state.

Pilot Study of Endothelin Receptor Blockade in Heart Failure with Diastolic Dysfunction and Pulmonary Hypertension (BADDHY-Trial).

BACKGROUND: In this multi-centre, randomised, placebo-controlled pilot trial, we investigated the clinical and haemodynamic effects of the endothelin-receptor blocker Bosentan in patients with heart failure, preserved ejection fraction and pulmonary hypertension (PH-HFpEF). MATERIALS AND METHODS: Eligible patients received either 12 weeks of Bosentan therapy, or a placebo drug. Patients were thereafter followed for a further period of 12 weeks without the study medication. At three points during the study (study Commencement, Week 12 and Week 24), a six-minute walk test (6MWT), echocardiographic and laboratory assessments were performed, as well as a quality of life survey. Right heart catheterisation (RHC) was undertaken at commencement only. The study was aborted early, after an interim analysis favoured the placebo. RESULTS: Six-minute walk distance (6MWD) did not change in the Bosentan group (309.7±96.3m (Commencement), 317.0±126.1m (Week 12), 307.0±84.4m (Week 24); p=0.86), but almost reached statistical significance in the placebo group from 328.8±79.6m, to 361.6±98.2m and 384.0±74.9m (Week 24); p=0.075. In the placebo group, estimated systolic pulmonary artery pressure (measured via echocardiography) significantly decreased (from 62.3±16.7mmHg [Commencement], 45.3±13.9mmHg [Week 12], to 44.6±14.5mmHg [Week 24]; p=0.014) as did right atrial pressure (13.1±5.3 [Commencement], 10.0±3.8 [Week 12], to 9.4±3.2 [Week 24]; p=0.046). CONCLUSION: Despite this study's limited sample size and premature cessation, it nevertheless suggests that endothelin receptor blockade in patients with PH-HFpEF may have no beneficial effects and could even be detrimental in comparison to a placebo.

Goal structure effects on social interaction: nondisabled and disabled elementary students.

This study compared social interaction behavior between nondisabled and disabled students, as a function of the way tasks were structured during a peer integration program. Of the eight pairs of students, four pairs were assigned to an individualistic goal-structured condition; the other four pairs, to a cooperative condition. For nondisabled students, the cooperative condition was associated with more social interaction during activity and free play sessions. For disabled students, the cooperative condition was associated with more social interaction during activity sessions, but not during free play sessions.