Predictors of 1-year survival in South African transcatheter aortic valve implant candidates

Background. Transcatheter aortic valve implantation (TAVI) has undergone rapid expansion internationally over the past 15 years. In view of resource constraints in developing countries, a major challenge in applying this technology lies in identifying patients most likely to benefit. The development of a risk prediction model for TAVI has proved elusive, with a reported area under the curve (AUC) of 0.6 - 0.65. The available models were developed in a First-World setting and may not be applicable to South Africa (SA).Objectives. To evaluate novel indicators and to develop a TAVI risk prediction model unique to the SA context. The current work represents the important initial steps of derivation cohort risk model development and internal validation.Methods. Seven-year experience with 244 successive TAVI implants in three centres in Western Cape Province, SA, was used to derive risk parameters. All outcomes are reported in accordance with the Valve Academic Research Consortium definitions. Multiple preprocedural variables were assessed for their impact on 1-year survival using univariate and multivariate models.Results. Factors found not to correlate with 1-year survival included age, renal function and aortic valve gradients. The commonly used surgical risk prediction models (Society of Thoracic Surgeons score and EuroSCORE) showed no correlation with outcomes. Factors found to correlate best with 1-year survival on multivariate analysis were preprocedural body mass index (BMI) (favouring higher BMI), preprocedural left ventricular end-diastolic dimension (LVED) and ejection fraction (EF) (favouring smaller LVED and higher EF), absence of atrial fibrillation, and three novel parameters: independent living, ability to drive a car, and independent food acquisition/cooking. Discriminant analysis of these factors yielded an AUC of 0.8 (95% confidence interval 0.7 - 0.9) to predict 1-year survival, with resubstitution sensitivities and specificities of 72% and 71%, respectively.Conclusions. Apart from existing predictors, we identified three novel risk predictors (independent living, ability to drive a car, and independent food acquisition/cooking) for 1-year survival in TAVI candidates. These novel parameters performed well in this early evaluation, with an AUC for predicting 1-year survival higher than the AUCs for many of the internationally derived parameters. The parameters are inexpensive and easy to obtain at the initial patient visit. If validated prospectively in external cohorts, they may be applicable to other resource-constrained environments.

Tyrosine-Phosphorylated Caveolin-1 Blocks Bacterial Uptake by Inducing Vav2-RhoA-Mediated Cytoskeletal Rearrangements

During the early stages of infection, Neisseria gonorrhoeae triggers a phosphotyrosine-dependent Cav1-Vav2-RhoA signaling cascade that promotes the pathogen's extracellular state

RhoE Is Regulated by Cyclic AMP and Promotes Fusion of Human BeWo Choriocarcinoma Cells

Fusion of placental villous cytotrophoblasts with the overlying syncytiotrophoblast is essential for the maintenance of successful pregnancy, and disturbances in this process have been implicated in pathological conditions such as pre-eclampsia and intra-uterine growth retardation. In this study we examined the role of the Rho GTPase family member RhoE in trophoblast differentiation and fusion using the BeWo choriocarcinoma cell line, a model of villous cytotrophoblast fusion. Treatment of BeWo cells with the cell permeable cyclic AMP analogue dibutyryl cyclic AMP (dbcAMP) resulted in a strong upregulation of RhoE at 24h, coinciding with the onset of fusion. Using the protein kinase A (PKA)-specific cAMP analogue N6-phenyl-cAMP, and a specific inhibitor of PKA (14–22 amide, PKI), we found that upregulation of RhoE by cAMP was mediated through activation of PKA signalling. Silencing of RhoE expression by RNA interference resulted in a significant decrease in dbcAMP-induced fusion. However, expression of differentiation markers human chorionic gonadotrophin and placental alkaline phosphatase was unaffected by RhoE silencing. Finally, we found that RhoE upregulation by dbcAMP was significantly reduced under hypoxic conditions in which cell fusion is impaired. These results show that induction of RhoE by cAMP is mediated through PKA and promotes BeWo cell fusion but has no effect on functional differentiation, supporting evidence that these two processes may be controlled by separate or diverging pathways

Protein tyrosine phosphatases expression during development of mouse superior colliculus

Protein tyrosine phosphatases (PTPs) are key regulators of different processes during development of the central nervous system. However, expression patterns and potential roles of PTPs in the developing superior colliculus remain poorly investigated. In this study, a degenerate primer-based reverse transcription-polymerase chain reaction (RT-PCR) approach was used to isolate seven different intracellular PTPs and nine different receptor-type PTPs (RPTPs) from embryonic E15 mouse superior colliculus. Subsequently, the expression patterns of 11 PTPs (TC-PTP, PTP1C, PTP1D, PTP-MEG2, PTP-PEST, RPTPJ, RPTPε, RPTPRR, RPTPσ, RPTPκ and RPTPγ) were further analyzed in detail in superior colliculus from embryonic E13 to postnatal P20 stages by quantitative real-time RT-PCR, Western blotting and immunohistochemistry. Each of the 11 PTPs exhibits distinct spatiotemporal regulation of mRNAs and proteins in the developing superior colliculus suggesting their versatile roles in genesis of neuronal and glial cells and retinocollicular topographic mapping. At E13, additional double-immunohistochemical analysis revealed the expression of PTPs in collicular nestin-positive neural progenitor cells and RC-2-immunoreactive radial glia cells, indicating the potential functional importance of PTPs in neurogenesis and gliogenesis

Goal-directed and habitual control in the basal ganglia: implications for Parkinson's disease

Progressive loss of the ascending dopaminergic projection in the basal ganglia is a fundamental pathological feature of Parkinson's disease. Studies in animals and humans have identified spatially segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. In patients with Parkinson's disease the loss of dopamine is predominantly in the posterior putamen, a region of the basal ganglia associated with the control of habitual behaviour. These patients may therefore be forced into a progressive reliance on the goal-directed mode of action control that is mediated by comparatively preserved processing in the rostromedial striatum. Thus, many of their behavioural difficulties may reflect a loss of normal automatic control owing to distorting output signals from habitual control circuits, which impede the expression of goal-directed action. © 2010 Macmillan Publishers Limited. All rights reserved

The role of diatom nanostructures in biasing diffusion to improve uptake in a patchy nutrient environment

Extent: 9 p.BACKGROUND: Diatoms are important single-celled autotrophs that dominate most lit aquatic environments and are distinguished by surficial frustules with intricate designs of unknown function. PRINCIPAL FINDINGS: We show that some frustule designs constrain diffusion to positively alter nutrient uptake. In nutrient gradients of 4 to 160 times over, 5 cm, the screened-chambered morphology of Coscincodiscus sp. biases the nutrient diffusion towards the cell by at least 3.8 times the diffusion to the seawater. In contrast, the open-chambers of Thalassiosira eccentrica produce at least a 1.3 times diffusion advantage to the membrane over Coscincodiscus sp. when nutrients are homogeneous. SIGNIFICANCE: Diffusion constraint explains the success of particular diatom species at given times and the overall success of diatoms. The results help answer the unresolved question of how adjacent microplankton compete. Furthermore, diffusion constraint by supramembrane nanostructures to alter molecular diffusion suggests that microbes compete via supramembrane topology, a competitive mechanism not considered by the standard smooth-surface equations used for nutrient uptake nor in microbial ecology and cell physiology.James G. Mitchell, Laurent Seuront, Mark J. Doubell, Dusan Losic, Nicolas H. Voelcker, Justin Seymour and Ratnesh La

Carrying capacity for finfish aquaculture. Part I-Near-field semi-analytic solutions

Abstract not availableJohn F. Middleton, Mark Doubel

Prokaryotic and diazotrophic population dynamics within a large oligotrophic inverse estuary

The ecology of microbial assemblages inhabiting classical (positive) estuaries has been well documented. However, we know relatively little about the microbial ecology of inverse (negative) estuaries, which exhibit different physical and hydrodynamic properties, including oligotrophy and hypersalinity. We investigated the dynamics of bacterioplankton communities in Spencer Gulf, an inverse estuary in temperate South Australia. We characterised patterns in the overall diversity and composition of the resident microbial assemblage, and tested the hypothesis that pelagic nitrogen-fixing bacteria (diazotrophs) could be an important functional group in the nutrient limited waters of the region. Prokaryotic and diazotrophic communities were evaluated using 16S ribosomal DNA and nifH amplicon tag pyrosequencing, respectively. Significant heterogeneity in microbial community composition and diazotrophic population structure was observed, which was driven by shifts in the relative importance of temperate vs. subtropical and oceanic vs. coastal ecotypes of Cyanobacteria throughout the inverse estuary. The globally significant unicellular cyanobacterium, UCYN-A ‘Candidatus Atelocyanobacterium thalassa’, was the dominant diazotrophic phylotype. Temperature, chlorophyll a and nitrogen availability were all significant drivers of bacterioplankton dynamics within the gulf. These results demonstrate the heterogeneous microbiology of inverse estuaries, indicating that specific abiotic and biotic characteristics select for discrete microbial communities, and that pelagic nitrogen fixation may be important in this temperate oligotrophic system.L.F. Messer, M. Doubell, T.C. Jeffries, M.V. Brown, J.R. Seymou

Predictors of 1-year survival in South African transcatheter aortic valve implant candidates

CITATION: Liebenberg, J. J., et al. 2020. Predictors of 1-year survival in South African transcatheter aortic valve implant candidates. South African Medical Journal, 110(6):491-496, doi:10.7196/SAMJ.2020.v110i6.14123.The original publication is available at http://www.samj.org.za/index.php/samj/article/view/12957Publication of this article was funded by the Stellenbosch University Open Access Fund.Background. Transcatheter aortic valve implantation (TAVI) has undergone rapid expansion internationally over the past 15 years. In view of resource constraints in developing countries, a major challenge in applying this technology lies in identifying patients most likely to benefit. The development of a risk prediction model for TAVI has proved elusive, with a reported area under the curve (AUC) of 0.6 - 0.65. The available models were developed in a First-World setting and may not be applicable to South Africa (SA). Objectives. To evaluate novel indicators and to develop a TAVI risk prediction model unique to the SA context. The current work represents the important initial steps of derivation cohort risk model development and internal validation. Methods. Seven-year experience with 244 successive TAVI implants in three centres in Western Cape Province, SA, was used to derive risk parameters. All outcomes are reported in accordance with the Valve Academic Research Consortium definitions. Multiple preprocedural variables were assessed for their impact on 1-year survival using univariate and multivariate models. Results. Factors found not to correlate with 1-year survival included age, renal function and aortic valve gradients. The commonly used surgical risk prediction models (Society of Thoracic Surgeons score and EuroSCORE) showed no correlation with outcomes. Factors found to correlate best with 1-year survival on multivariate analysis were preprocedural body mass index (BMI) (favouring higher BMI), preprocedural left ventricular end-diastolic dimension (LVED) and ejection fraction (EF) (favouring smaller LVED and higher EF), absence of atrial fibrillation, and three novel parameters: independent living, ability to drive a car, and independent food acquisition/cooking. Discriminant analysis of these factors yielded an AUC of 0.8 (95% confidence interval 0.7 - 0.9) to predict 1-year survival, with resubstitution sensitivities and specificities of 72% and 71%, respectively. Conclusions. Apart from existing predictors, we identified three novel risk predictors (independent living, ability to drive a car, and independent food acquisition/cooking) for 1-year survival in TAVI candidates. These novel parameters performed well in this early evaluation, with an AUC for predicting 1-year survival higher than the AUCs for many of the internationally derived parameters. The parameters are inexpensive and easy to obtain at the initial patient visit. If validated prospectively in external cohorts, they may be applicable to other resource-constrained environments.http://www.samj.org.za/index.php/samj/article/view/12957Publisher's versio