The role of fossils in interpreting the development of the Karoo Basin

Main articleThe Permo-Carboniferous to Jurassic aged rocks off the main Karoo Basin of South Africa are world renowned for the wealth of synapsid reptile and early dinosaur fossils, which have allowed a ten-fold biostratigraphic subdivision of the Karoo Supergroup to be erected. The role of fossils in interpreting the development of the Karoo Basin is not, however, restricted to biostratigraphic studies. Recent integrated sedimentological and palaeontological studies have helped in more precisely defining a number of problematical formational contacts within the Karoo Supergroup, as well as enhancing palaeoenvironmental reconstructions, and basin development models.Non

Biostratigraphy of the lower Burgersdorp Formation (Beaufort Group; Karoo Supergroup) of South Africa – implications for the stratigraphic ranges of early Triassic tetrapods

The Beaufort Group (Karoo Supergroup) of South Africa comprises a thick sequence of fluvio-lacustrine sedimentary rocks that accumulated in a landlocked, intracratonic foreland basin in southwestern Gondwana during the Middle Permian to Middle Triassic. To the south this basin was bounded by the Cape Fold Belt, which acted as the major source of both sediment and discharge. Rocks of the Beaufort Group are renowned for their rich fossil record and eight tetrapod-based biozones are currently recognized. The uppermost two biozones of the Beaufort Group, the Lystrosaurus and Cynognathus assemblage zones, record terrestrial biotic recovery following the Permo-Triassic mass extinction event. Stratigraphic overlap between these biozones occurs in the proximal sector, but their separation by an unconformity in the distal sector reflects the incomplete preservation of the sequence in this part of the basin. Our results afford chronostratographic control that impacts on current theories on the development of the Karoo Basin, and on the relative age of the sequence.South African Council for Geoscience, the University of the Witwatersrand and the National Research Foundation

Differential responses of rabbit ventricular and atrial transient outward current (Ito) to the Ito modulator NS5806

Transient outward potassium current (I(to)) in the heart underlies phase 1 repolarization of cardiac action potentials and thereby affects excitation–contraction coupling. Small molecule activators of I(to) may therefore offer novel treatments for cardiac dysfunction, including heart failure and atrial fibrillation. NS5806 has been identified as a prototypic activator of canine I(to). This study investigated, for the first time, actions of NS5806 on rabbit atrial and ventricular I(to). Whole cell patch‐clamp recordings of I(to) and action potentials were made at physiological temperature from rabbit ventricular and atrial myocytes. 10 μmol/L NS5806 increased ventricular I(to) with a leftward shift in I(to) activation and accelerated restitution. At higher concentrations, stimulation of I(to) was followed by inhibition. The EC (50) for stimulation was 1.6 μmol/L and inhibition had an IC (50) of 40.7 μmol/L. NS5806 only inhibited atrial I(to) (IC (50) of 18 μmol/L) and produced a modest leftward shifts in I(to) activation and inactivation, without an effect on restitution. 10 μmol/L NS5806 shortened ventricular action potential duration (APD) at APD (20)‐APD (90) but prolonged atrial APD. NS5806 also reduced atrial AP upstroke and amplitude, consistent with an additional atrio‐selective effect on Na(+) channels. In contrast to NS5806, flecainide, which discriminates between Kv1.4 and 4.x channels, produced similar levels of inhibition of ventricular and atrial I(to). NS5806 discriminates between rabbit ventricular and atrial I(to,) with mixed activator and inhibitor actions on the former and inhibitor actions against the later. NS5806 may be of significant value for pharmacological interrogation of regional differences in native cardiac I(to)

Psychosocial interventions for improving quality of life outcomes in adults undergoing strabismus surgery (Protocol)

This is the protocol for a review and there is no abstract. The objectives are as follows: To investigate the effects of psychosocial interventions versus no intervention on quality of life and psychosocial outcomes in adults undergoing strabismus surgery. The primary objective is to assess whether patients who have taken part in a sychosocial intervention prior to their strabismus surgery report significantly improved quality of life compared to those who receive standard care,i.e. strabismus surgery alone. The secondary outcome measures will include anxiety, depression, social anxiety and social avoidance, as well as degree of success in terms of surgical outcome

Inducing Ito,f and phase 1 repolarization of the cardiac action potential with a Kv4.3/KChIP2.1 bicistronic transgene

The fast transient outward potassium current (I(to,f)) plays a key role in phase 1 repolarization of the human cardiac action potential (AP) and its reduction in heart failure (HF) contributes to the loss of contractility. Therefore, restoring I(to,f) might be beneficial for treating HF. The coding sequence of a P2A peptide was cloned, in frame, between Kv4.3 and KChIP2.1 genes and ribosomal skipping was confirmed by Western blotting. Typical I(to,f) properties with slowed inactivation and accelerated recovery from inactivation due to the association of KChIP2.1 with Kv4.3 was seen in transfected HEK293 cells. Both bicistronic components trafficked to the plasmamembrane and in adenovirus transduced rabbit cardiomyocytes both t-tubular and sarcolemmal construct labelling appeared. The resulting current was similar to I(to,f) seen in human ventricular cardiomyocytes and was 50% blocked at ~0.8 mmol/l 4-aminopyridine and increased ~30% by 5 μmol/l NS5806 (an I(to,f) agonist). Variation in the density of the expressed I(to,f), in rabbit cardiomyocytes recapitulated typical species-dependent variations in AP morphology. Simultaneous voltage recording and intracellular Ca(2+) imaging showed that modification of phase 1 to a non-failing human phenotype improved the rate of rise and magnitude of the Ca(2+) transient. I(to,f) expression also reduced AP triangulation but did not affect I(Ca,L) and I(Na) magnitudes. This raises the possibility for a new gene-based therapeutic approach to HF based on selective phase 1 modification

What do patients with strabismus expect post surgery? The development and validation a questionnaire

Aims: To develop and validate a short questionnaire to assess patients’ expectations about outcomes post strabismus surgery. Methods: Questionnaire items were extracted from previous literature and reviewed by a multidisciplinary team. A cross-sectional study was then undertaken with 220 adult patients due to undergo strabismus surgery. Participants completed the 17-item questionnaire. Scale structure was explored using principal component analysis (PCA), and the subscales analysed in relation to demographic and clinical characteristics and psychosocial well-being in order to establish validity. Results: PCA revealed a 3-factor solution for the Expectations of Strabismus Surgery Questionnaire (ESSQ): (a) intimacy and appearance-related issues, (b) visual functioning, (c) social relationships. This 3-factor solution explained 59.30% of the overall variance in the ESSQ. Internal consistency, content and nomological and concurrent validity were considered acceptable. Conclusions: Patients with strabismus have high expectations about their postsurgical outcomes. This questionnaire provides a useful tool to assess the expectations patients have about their surgery, whether these expectations change over time and how they impact on postsurgical outcomes

Arrhythmogenic late Ca2+sparks in failing heart cells and their control by action potential configuration

Sudden death in heart failure patients is a major clinical problem worldwide, but it is unclear how arrhythmogenic early afterdepolarizations (EADs) are triggered in failing heart cells. To examine EAD initiation, high-sensitivity intracellular Ca2+ measurements were combined with action potential voltage clamp techniques in a physiologically relevant heart failure model. In failing cells, the loss of Ca2+ release synchrony at the start of the action potential leads to an increase in number of microscopic intracellular Ca2+ release events (“late” Ca2+ sparks) during phase 2–3 of the action potential. These late Ca2+ sparks prolong the Ca2+ transient that activates contraction and can trigger propagating microscopic Ca2+ ripples, larger macroscopic Ca2+ waves, and EADs. Modification of the action potential to include steps to different potentials revealed the amount of current generated by these late Ca2+ sparks and their (subsequent) spatiotemporal summation into Ca2+ ripples/waves. Comparison of this current to the net current that causes action potential repolarization shows that late Ca2+ sparks provide a mechanism for EAD initiation. Computer simulations confirmed that this forms the basis of a strong oscillatory positive feedback system that can act in parallel with other purely voltage-dependent ionic mechanisms for EAD initiation. In failing heart cells, restoration of the action potential to a nonfailing phase 1 configuration improved the synchrony of excitation–contraction coupling, increased Ca2+ transient amplitude, and suppressed late Ca2+ sparks. Therapeutic control of late Ca2+ spark activity may provide an additional approach for treating heart failure and reduce the risk for sudden cardiac death