Right ventricular function during exercise in children after heart transplantation.

Aims: Right ventricular (RV) dysfunction is a common problem after heart transplant (HTx). In this study, we used semi-supine bicycle ergometry (SSBE) stress echocardiography to evaluate RV systolic and diastolic reserve in paediatric HTx recipients. Methods and results: Thirty-nine pediatric HTx recipients and 23 controls underwent stepwise SSBE stress echocardiography. Colour tissue doppler imaging (TDI) peak systolic (s') and peak diastolic (e') velocities, myocardial acceleration during isovolumic contraction (IVA), and RV free wall longitudinal strain were measured at incremental heart rates (HR). The relationship with increasing HR was evaluated for each parameter by plotting values at each stage of exercise versus HR using linear and non-linear regression models. At rest, HTx recipients had higher HR with lower TDI velocities (s': 5.4 ± 1.7 vs. 10.4 ± 1.8 cm/s, P < 0.001; e': 6.4 ± 2.2 vs.12 ± 2.4 cm/s, P < 0.001) and RV IVA values (IVA: 1.2 ± 0.4 vs. 1.6 ± 0.8 m/s2, P = 0.04), while RV free wall longitudinal strain was similar between groups. At peak exercise, HR was higher in controls and all measurements of RV function were significantly lower in HTx recipients, except for RV free wall longitudinal strain. When assessing the increase in each parameter vs. HR, the slopes were not significantly different between patients and controls except for IVA, which was lower in HTx recipients. Conclusion: In pediatric HTx recipients RV systolic and diastolic functional response to exercise is preserved with a normal increase in TDI velocities and strain values with increasing HR. The blunted IVA response possibly indicates a mildly decreased RV contractile response but it requires further investigation.

Impact of surgical pulmonary valve replacement on ventricular mechanics in children with repaired tetralogy of Fallot.

Impaired ventricular myocardial mechanics are observed in patients with repaired tetralogy of Fallot (rTOF). Effects of pulmonary valve replacement (PVR) on ventricular remodeling are controversial. The objective was to assess the impact of surgical PVR on ventricular mechanics in pediatric patients after rTOF. Speckle-tracking analysis was performed in 50 rTOF children, aged 12.6 ± 3.3 years, pre-operatively and 14.5 ± 2.2 months post-PVR. Early post-operative studies 2.2 ± 0.6 months post-PVR were performed in 28 patients. Cardiac magnetic resonance (CMR) pre- and post-PVR was collected. Mid-term post-PVR right ventricular (RV) longitudinal strain increased above pre-operative strain (-19.2 ± 2.7 to -22.0 ± 3.0%, p < 0.001) with increases observed in individual RV segments. Left ventricular (LV) strain did not differ at medium-term follow-up. LV and RV longitudinal strain was reduced early post-operatively, followed by recovery of biventricular systolic strain by mid-term follow-up. CMR RV end-diastolic indexed volumes correlated with RV strain pre-operatively (r = 0.432, p = 0.005) and at mid-term follow-up (r = 0.532, p = 0.001). Volume-loaded RVs had reduced early RV basal longitudinal strain compared to pressure-loading conditions. Reversed basal counterclockwise rotation was associated with lower mid-term global LV and basal RV strain compared to patients with normal rotation. An increase in mid-term global and regional RV strain beyond pre-operative values suggests positive RV remodeling and adaptation occurs in children post-PVR. Patients with larger pre-operative RV volumes had lower RV strain post-operatively. The impact of LV rotation on RV mechanics highlights the presence of ventriculo-ventricular interactions. These findings have important clinical implications in pediatric rTOF patients towards identifying pre-operative factors that predict RV post-operative remodeling.

Transforming growth factor beta (TGF-ß) isomers influence cell detachment of MG-63 bone cells.

Bone repair and wound healing are modulated by different stimuli. There is evidence that Transforming Growth Factor-beta (TGF-ß) super-family of cytokines have significant effects on bone structure by regulating the replication and differentiation of chondrocytes, osteoblasts and osteoclasts. There is also significant evidence that interactions with extracellular matrix molecules influence cell behaviour. In this study cell surface attachment was examined via a trypsinization assay using various TGF-ß isomers in which the time taken to trypsinize cells from the surface provided a means of assessing the strength of attachment. Three TGF-ß isomers (TGF-ß1, 2 and 3), four combined forms (TGF-ß(1+2), TGF-ß(1+3), TGF-ß(2+3) and TGF-ß(1+2+3)) along with four different controls (BSA, HCl, BSA/HCl and negative control) were investigated in this study. The results indicated that treatment with TGF-ß1, 2, 3 and HCl decreased cell attachment, however, this effect was significantly greater in the case of TGF-ß3 (p<0.001) indicating perhaps that TGF-ß3 does not act alone in cell detachment, but instead functions synergistically with signalling pathways that are dependent on the availability of hydrogen ions. Widefield Surface Plasmon Resonance (WSPR) microscope was also used to investigate cell surface interactions.

Tracking traction force changes of single cells on the liquid crystal surface.

Cell migration is a key contributor to wound repair. This study presents findings indicating that the liquid crystal based cell traction force transducer (LCTFT) system can be used in conjunction with a bespoke cell traction force mapping (CTFM) software to monitor cell/surface traction forces from quiescent state in real time. In this study, time-lapse photo microscopy allowed cell induced deformations in liquid crystal coated substrates to be monitored and analyzed. The results indicated that the system could be used to monitor the generation of cell/surface forces in an initially quiescent cell, as it migrated over the culture substrate, via multiple points of contact between the cell and the surface. Future application of this system is the real-time assaying of the pharmacological effects of cytokines on the mechanics of cell migration.

Effects of different transforming growth factor beta (TGF-ß) isomers on wound closure of bone cell monolayers.

This study aimed at determining the role of the transforming growth factor-beta (TGF-ß) isomers and their combinations in bone cell behaviour using MG63 cells. The work examined how TGF-ß1, 2 and 3 and their solvent and carrier (HCl and BSA, respectively) effected cell morphology, cell proliferation and integrin expression. This study also aimed at examining how the TGF-ßs and their solvent and carrier influenced wound closure in an in vitro wound closure model and how TGF-ßs influence extracellular matrix (ECM) secretion and integrin expression. The wound healing response in terms of healing rate to the TGF-ßs and their solvent/carrier was investigated in 300 µm ± 10-30 µm SD wide model wounds induced in fully confluent monolayers of MG63 bone cells. The effect of different TGF-ß isomers and their combinations on proliferation rate and cell length of human bone cells were also assessed. Immunostaining was used to determine if TGF-ßs modifies integrin expression and ECM secretion by the bone cells. Imaging with WSPR allowed observation of the focal contacts without the need for immunostaining. The wound healing results indicated that TGF-ß3 has a significant effect on the wound healing process and its healing rate was found to be higher than the control (p < 0.001), TGF-ß1 (p < 0.001), TGF-ß2 (p < 0.001), BSA/HCl (p < 0.001) and HCl (p < 0.001) in ascending order. It was also found that TGF-ß1 and TGF-ß2 treatment significantly improved wound closure rate in comparison to the controls (p < 0.001). All TGF-ß combinations induced a faster healing rate than the control (p < 0.001). It was expected that the healing rate following treatment with TGF-ß combinations would be greater than those healing rates following treatments with TGF-ß isomers alone, but this was not the case. The results also suggest that cell morphological changes were observed significantly more in cells treated with TGF-ß(2 + 3) and TGF-ß(1 + 3) (p < 0.001). Any cell treated with TGF-ß1, TGF-ß(1 + 2) and TGF-ß(1 + 2 + 3) showed significantly less elongation compared to the control and other TGF-ß isomers. In terms of proliferation rate, TGF-ß3 and TGF-ß(2 + 3) increased cell numbers more than TGF-ß1, TGF-ß2 and other combinations. TGF-ß1 and its combinations did not show significant proliferation and attachment compared to the control. Immunostaining indicated that treatment with TGF-ß3 significantly enhanced the secretion of collagen type I, fibronectin and integrins α3 and ß1. The WSPR experiments also indicated that TGF-ßs influenced the distribution of focal contacts. In conclusion, combining TGF-ß3 with any other TGF-ß isomer resulted in a faster model wound closure rate (p < 0.001), while treatment with TGF-ß1 in any TGF-ß combination reduced the healing rate (p < 0.001). It can therefore be concluded that the presence of TGF-ß1 has an inhibitory effect on bone wound healing while TGF-ß3 had the opposite effect and increased the rate of wound closure in a 2 dimensional cell culture environment.

Using mathematical modelling to inform on the ability of stormwater ponds to improve the water quality of urban runoff.

This paper concerns the mathematical modelling of flow and solute transport through stormwater ponds. The model is based on appropriate lumped system conservation equations that are solved using standard numerical techniques. The model was used to route a first flush pollution scenario through a cylindrical pond for 16 combinations of elevation and diameter of a submerged pipe outlet, in conjunction with a high level weir. Higher pipe elevations and smaller pipe diameters created larger pond volumes and hence led to greater dilution of the pollutant. In contrast, lower pipe elevations created larger storage volumes, leading to better flow attenuation. Interestingly, larger pipe diameters improved peak flow attenuation, even though the storage used decreased.

Characterization of a Vascular Wilt of Erythroxylum coca Caused by Fusarium oxysporum f. sp. erythroxyli Forma Specialis Nova.

A new forma specialis of Fusarium oxysporum (F. oxysporum f. sp. erythroxyli) pathogenic to Erythroxylum coca and E. novogranatense is described. The pathogen was isolated from the vascular tissue of diseased plants from an Erythroxylum plantation in Hawaii. This pathogen causes vascular wilt symptoms and death in both E. coca and E. novogranatense plants as soon as 7 weeks after soil infestation. The pathogenicity of seven isolates from the affected field was determined in field and growth-chamber studies. Genetic variation was not detected among the seven Hawaiian isolates, using arbitrarily primed polymerase chain reaction. The seven isolates could be differentiated from a strain isolated from a diseased E. coca plant from South America. All Hawaiian isolates and the South American isolate belonged to a single vegetative compatibility group.