Investigating Arrhythmia Potential in Cardiac Myocytes in Presence of Long QT Syndrome

Long QT Syndrome (LQTS) is an increasingly studied condition that leads to potentially fatal heart rhythm disorders, called arrhythmias, and sudden cardiac death. The alterations in the electrocardiograms (ECGs) seen in LQTS patients is caused by mutations to genes related to ion channels in cardiac cells. Computational modeling allows the mechanistic study of these ion channel mutations in LQTS by providing quantitative predictors of cardiac behavior in human and rabbit heart models. This work hypothesizes that the repolarization reserve in cardiac Purkinje cells (PC), that form the cardiac conduction system, is lower than that of ventricular myocytes (VM), resulting in a higher propensity of electrophysiological abnormalities in the form of spontaneous activity, particularly early and delayed afterdepolarizations (EADs and DADs, respectively). To investigate this hypothesis, detailed computational methods were created by incorporating experimental data. The computer models were then utilized to reproduce the experimentally observed behavior in single cells as well as 3-dimensional ventricular models. The computational results show more profound effects of the LQTS mutations on action potential duration (APD) prolongation in PCs when compared to VMs. Ectopic beats exist in isoproterenol conditions for human PCs. Future research includes determining the effect of these APD differences on the entirety of the heart using an anatomical 3D model of a rabbit heart

Maternal taurine supplementation in rats partially prevents the adverse effects of early-life protein deprivation on b-cell function and insulin sensitivity

Dietary protein restriction during pregnancy and lactation in rats impairs b-cell function and mass in neonates and leads to glucose intolerance in adult offspring. Maternal taurine (Tau) supplementation during pregnancy in rats restores b-cell function and mass in neonates, but its long-term effects are unclear. The prevention of postnatal catch-up growth has been suggested to improve glucose tolerance in adult offspring of low-protein (LP)-fed mothers. The objective of this study was to examine the relative contribution of b-cell dysfunction and insulin resistance to impaired glucose tolerance in 130-day-old rat offspring of LP-fed mothers and the effects of maternal Tau supplementation on b-cell function and insulin resistance in these offspring. Pregnant rats were fed i) control, ii) LP, and iii) LPCTau diets during gestation and lactation. Offspring were given a control diet following weaning. A fourth group consisting of offspring of LP-fed mothers, maintained on a LP diet following weaning, was also studied (LP-all life). Insulin sensitivity in the offspring of LP-fed mothers was reduced in females but not in males. In both genders, LP exposure decreased b-cell function. Tau supplementation improved insulin sensitivity in females and b-cell function in males. The LP-all life diet improved b-cell function in males. We conclude that i) maternal Tau supplementation has persistent effects on improving glucose metabolism (b-cell function and insulin sensitivity) in adult rat offspring of LP-fed mothers and ii) increasing the amount of protein in the diet of offspring adapted to a LP diet after weaning may impair glucose metabolism (b-cell function) in a gender-specific manner.Fil: Tang, Christine. University Of Toronto; Canadá;Fil: Marchand, K.elly. University of Western Ontario. Lawson Health Research Institute; Canadá;Fil: Lam, Loretta. University Of Toronto; Canadá;Fil: Lux, Victoria Adela R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Thyssen, Sandra M.. University of Western Ontario. Lawson Health Research Institute; Canadá;Fil: Guo, June. University Of Toronto; Canadá;Fil: Giacca, A.dria. University Of Toronto; Canadá;Fil: Arany, Edith. University of Western Ontario. Lawson Health Research Institute; Canadá

Maternal taurine supplementation in rats partially prevents the adverse effects of early-life protein deprivation on β-cell function and insulin sensitivity

Dietary protein restriction during pregnancy and lactation in rats impairs β-cell function and mass in neonates and leads to glucose intolerance in adult offspring. Maternal taurine (Tau) supplementation during pregnancy in rats restores β-cell function and mass in neonates, but its long-term effects are unclear. The prevention of postnatal catch-up growth has been suggested to improve glucose tolerance in adult offspring of low-protein (LP)-fed mothers. The objective of this study was to examine the relative contribution of β-cell dysfunction and insulin resistance to impaired glucose tolerance in 130-day-old rat offspring of LP-fed mothers and the effects of maternal Tau supplementation on β-cell function and insulin resistance in these offspring. Pregnant rats were fed i) control, ii) LP, and iii) LP+Tau diets during gestation and lactation. Offspring were given a control diet following weaning. A fourth group consisting of offspring of LP-fed mothers, maintained on a LP diet following weaning, was also studied (LP-all life). Insulin sensitivity in the offspring of LP-fed mothers was reduced in females but not in males. In both genders, LP exposure decreased β-cell function. Tau supplementation improved insulin sensitivity in females and β-cell function in males. The LP-all life diet improved β-cell function in males. We conclude that i) maternal Tau supplementation has persistent effects on improving glucose metabolism (β-cell function and insulin sensitivity) in adult rat offspring of LP-fed mothers and ii) increasing the amount of protein in the diet of offspring adapted to a LP diet after weaning may impair glucose metabolism (β-cell function) in a gender-specific manner. © 2013 Society for Reproduction and Fertility

Improved Quality of Life Following Addiction Treatment Is Associated with Reductions in Substance Use

People seeking treatment for substance use disorders (SUD) ultimately aspire to improve their quality of life (QOL) through reducing or ceasing their substance use, however the association between these treatment outcomes has received scant research attention. In a prospective, multi-site treatment outcome study (‘Patient Pathways’), we recruited 796 clients within one month of intake from 21 publicly funded addiction treatment services in two Australian states, 555 (70%) of whom were followed-up 12 months later. We measured QOL at baseline and follow-up using the WHOQOL-BREF (physical, psychological, social and environmental domains) and determined rates of “SUD treatment success” (past-month abstinence or a statistically reliable reduction in substance use) at follow-up. Mixed effects linear regression analyses indicated that people who achieved SUD treatment success also achieved significantly greater improvements in QOL, relative to treatment non-responders (all four domains p 0.001). Paired t-tests indicated that non-responders significantly improved their social (p = 0.007) and environmental (p = 0.033) QOL; however, their psychological (p = 0.088) and physical (p = 0.841) QOL did not significantly improve. The findings indicate that following treatment, QOL improved in at least some domains, but that reduced substance use was associated with both stronger and broader improvements in QOL. Addressing physical and psychological co-morbidities during treatment may facilitate reductions in substance use

Speaker gaze increases information coupling between infant and adult brains

When infants and adults communicate, they exchange social signals of availability and communicative intention such as eye gaze. Previous research indicates that when communication is successful, close temporal dependencies arise between adult speakers’ and listeners’ neural activity. However, it is not known whether similar neural contingencies exist within adult-infant dyads. Here, we used dual-electroencephalography to assess whether direct gaze increases neural coupling between adults and infants during screen-based and live interactions. In Experiment 1 (N=17), infants viewed videos of an adult who was singing nursery rhymes with (a) Direct gaze (looking forward); (b) Indirect gaze (head and eyes averted by 20°); or (c) Direct-Oblique gaze (head averted but eyes orientated forward). In Experiment 2 (N=19), infants viewed the same adult in a live context, singing with Direct or Indirect gaze. Gaze-related changes in adult-infant neural network connectivity were measured using Partial Directed Coherence. Across both experiments, the adult had a significant (Granger)-causal influence on infants’ neural activity, which was stronger during Direct and Direct-Oblique gaze relative to Indirect gaze. During live interactions, infants conversely also influenced the adult more during Direct than Indirect gaze. Furthermore, infants vocalised more frequently during live Direct gaze, and individual infants who vocalized longer also elicited stronger synchronisation from the adult. This is the first demonstration that direct gaze strengthens bi-directional adult-infant neural connectivity during communication. Thus, ostensive social signals could act to bring brains into mutual temporal alignment, creating a joint-networked state that is structured to facilitate information transfer during early communication and learning

Determinants of the dynamic cerebral critical closing pressure response to changes in mean arterial pressure

Objective. Cerebral critical closing pressure (CrCP) represents the value of arterial blood pressure (BP) where cerebral blood flow (CBF) becomes zero. Its dynamic response to a step change in mean BP (MAP) has been shown to reflect CBF autoregulation, but robust methods for its estimation are lacking. We aim to improve the quality of estimates of the CrCP dynamic response. Approach. Retrospective analysis of 437 healthy subjects (aged 18–87 years, 218 males) baseline recordings with measurements of cerebral blood velocity in the middle cerebral artery (MCAv, transcranial Doppler), non-invasive arterial BP (Finometer) and end-tidal CO2 (EtCO2, capnography). For each cardiac cycle CrCP was estimated from the instantaneous MCAv-BP relationship. Transfer function analysis of the MAP and MCAv (MAP-MCAv) and CrCP (MAP-CrCP) allowed estimation of the corresponding step responses (SR) to changes in MAP, with the output in MCAv (SRVMCAv) representing the autoregulation index (ARI), ranging from 0 to 9. Four main parameters were considered as potential determinants of the SRVCrCP temporal pattern, including the coherence function, MAP spectral power and the reconstruction error for SRVMAP, from the other three separate SRs. Main results. The reconstruction error for SRVMAP was the main determinant of SRVCrCP signal quality, by removing the largest number of outliers (Grubbs test) compared to the other three parameters. SRVCrCP showed highly significant (p < 0.001) changes with time, but its amplitude or temporal pattern was not influenced by sex or age. The main physiological determinants of SRVCrCP were the ARI and the mean CrCP for the entire 5 min baseline period. The early phase (2–3 s) of SRVCrCP response was influenced by heart rate whereas the late phase (10–14 s) was influenced by diastolic BP. Significance. These results should allow better planning and quality of future research and clinical trials of novel metrics of CBF regulation