Kv7 and Kv11 channels in myometrial regulation.

Ion channels play a key role in defining myometrial contractility. Modulation of ion channel populations is proposed to underpin gestational changes in uterine contractility associated with the transition from uterine quiescence to active labour. Of the myriad ion channels present in the uterus, this article will focus upon potassium channels encoded by the KCNQ genes and ether-à-go-go-related (ERG) genes. Voltage-gated potassium channels encoded by KCNQ and ERG (termed Kv7 and Kv11, respectively) are accepted as major determinants of neuronal excitability and the duration of the cardiac action potential. However, there is now growing appreciation that these ion channels have a major functional impact in vascular and non-vascular smooth muscle. Moreover, Kv7 channels may be potential therapeutic targets for the treatment of preterm labour

The Rain Gods’ Rebellion

"The Rain Gods’ Rebellion examines Nahua oral narratives to illuminate the cultural basis of the 1977–1984 rebellion against the local Hispanic elite in Huitzilan de Serdán, Mexico. Drawing from forty years of fieldwork in the region, James M. Taggart traces the sociopolitical role of Nahua rain gods—who took both human and divine forms—back hundreds of years and sheds new light on the connections between social experiences and the Nahua understanding of water and weather in stories. As Taggart shows, Nahua tales of the rain gods’ rebellion anticipated the actual 1977 land invasion in Huitzilan, in which some 200–300 Nahua were killed. The Rain Gods’ Rebellion reveals how local culture evolves from the expression of unrest to organized insurgency and then into collective memory. Taggart records a tradition of storytelling in which Nahuas radicalized themselves through recounting the rain gods’ stories—stories of the gods organizing and striking with bolts of lightning the companion spirits of autocratic local leaders who worked closely with mestizos. The tales are part of a tradition of resisting the friars’ efforts to convert the Nahuas, Totonacs, Otomi, and Tepehua to Christianity and inspiring nativistic movements against invading settlers. Providing a rare longitudinal look at the cultural basis of this grassroots insurgency, The Rain Gods’ Rebellion offers rare insight into the significance of oral history in forming Nahua collective memory and, by extension, culture. It will be of significance to scholars of Indigenous studies, anthropology, oral history, and violence studies, as well as linguistic anthropologists and sociolinguists.

What makes a successful transition from primary to secondary school?

This report presents the findings of a sub-study on transitions undertaken as part of the Effective Pre-school, Primary and Secondary Education 3-14 (EPPSE 3-14 project) a major longitudinal study investigating the influence of pre-school, primary and secondary school on children’s cognitive and social/behavioural development in England. The transitions sub-study of more than 500 children and families sheds light on current transition practices and highlights what helps and hinders a successful transition. It takes into account the influence of child and family background characteristics such as socio-economic status (SES) and gender. It suggests how the transition experience could be improved to enhance the smooth continuity between primary and secondary school. By adopting a mixed methods approach, the study investigated the issues related to transition for four distinctive groups: Local Authorities, children, parents and schools. Officers in six Local Authorities were asked about the way transition was dealt with in their Authority. Children in their first term at secondary school completed a questionnaire on their thoughts and experiences of transition, and the study also sought their parents’ opinions in order to illustrate the whole family’s experience. Finally, there were twelve case studies selected from the respondents of the questionnaire because of their positive experiences of transition. These involved interviews with the children and their primary and secondary teachers. This provided further details of the systems in place that support the transition processes between school phases. The sample was drawn from children and families in the wider EPPSE project. 1190 children from the EPPSE sample made a transition at the end of the 2005-06 academic year. Responses were received from 550 children (a 46% response rate) and 569 parents (a 48% response rate) from across England drawn from 6 Local Authorities (Shire County, Inner London borough, Midlands/Metropolitan region, East Anglia area, and two authorities in the North East). Children were recruited to the case studies using stratified selection to get a balanced mix by region, gender, socio-economic status (SES) and ethnicity. A wide range of data, already available from the main EPPSE study was used to complement the analyses

A multivariate time-frequency approach for tracking QT variability changes unrelated to heart rate variability

The beat-to-beat variability of the QT interval (QTV) is a marker of ventricular repolarization (VR) dynamics and it has been suggested as an index of sympathetic ventricular outflow and cardiac instability. However, QTV is also affected by RR (or heart rate) variability (RRV), and QTV due to RRV may reduce QTV specificity as a VR marker. Therefore, it would be desirable to separate QTV due to VR dynamics from QTV due to RRV. To do that, previous work has mainly focused on heart rate corrections or time-invariant autoregressive models. This paper describes a novel framework that extends classical multiple inputs/single output theory to the time-frequency (TF) domain to quantify QTV and RRV interactions. Quadratic TF distributions and TF coherence function are utilized to separate QTV into two partial (conditioned) spectra representing QTV related and unrelated to RRV, and to provide an estimates of intrinsic VR dynamics. In a simulation study, a time-varying ARMA model was used to generate signals representing realistic RRV and VR dynamics with controlled instantaneous frequencies and powers. The results demonstrated that the proposed methodology is able to accurately track changes in VR dynamics, with a correlation between theoretical and estimated patterns higher than 0.88. Data from healthy volunteers undergoing a tilt table test were analyzed and representative examples are discussed. Results show that the QTV unrelated to RRV dynamics quickly increased during orthostatic challenge

Major health-related behaviours and mental well-being in the general population : the health survey for England

Background: Major behavioural risk factors are known to adversely affect health outcomes and be strongly associated with mental illness. However, little is known about the association of these risk factors with mental well-being in the general population. We sought to examine behavioural correlates of high and low mental well-being in the Health Survey for England. Methods: Participants were 13 983 adults, aged 16 years and older (56% females), with valid responses for the combined 2010 and 2011 surveys. Mental well-being was assessed using the Warwick-Edinburgh Mental Well-being Scale (WEMWBS). ORs of low and high mental well-being, compared to the middle-range category, were estimated for body mass index (BMI), smoking, drinking habits, and fruit and vegetable intake. Results: ORs for low mental well-being were increased in obese individuals (up to 1.72, 95% CI 1.26 to 2.36 in BMI 40+ kg/m2). They increased in a linear fashion with increasing smoking (up to 1.98, 95% CI 1.55 to 2.53, >20 cigarettes/day) and with decreasing fruit and vegetable intake (up to 1.53, 95% CI 1.24 to 1.90, <1 portion/day); whereas ORs were reduced for sensible alcohol intake (0.78, 95% CI 0.66 to 0.91, ≤4 units/day in men, ≤3 units/day in women). ORs for high mental well-being were not correlated with categories of BMI or alcohol intake. ORs were reduced among ex-smokers (0.81, 95% CI 0.71 to 0.92), as well as with lower fruit and vegetable intake (up to 0.79, 95% CI 0.68 to 0.92, 1 to <3 portions/day). Conclusions; Along with smoking, fruit and vegetable consumption was the health-related behaviour most consistently associated with mental well-being in both sexes. Alcohol intake and obesity were associated with low, but not high mental well-being

Population of human ventricular cell models calibrated with in vivo measurements unravels ionic mechanisms of cardiac alternans

Cardiac alternansis an important risk factor in cardiac physiology, and is related to the initiation of many pathophysiological conditions. However, the mechanisms underlying the generation of alternans remain unclear. In this study, we used a population of computational human ventricle models based onthe O’Hara model [1] to explore the effect of 11 key factors experimentally reported to be related to alternans. In vivo experimental datasets coming from patients undergoing cardiac surgery were used in the calibration of our in silico population of models. The calibrated models in the population were divided into two groups (Normal and Alternans) depending on alternans occurrence. Our results showed that there were significant differences in the following 5 ionic currents between the two groups: fast sodium current, sodium calcium exchanger current, sodium potassium pump current, sarcoplasmic reticulum (SR) calcium release flux and SR calcium reuptake flux. Further analysis indicated that fast sodium current and SR calcium uptake were the two most significant currents that contributed to voltage and calcium alternans generation, respectively

Optimization of the global re-entry vulnerability index to minimise cycle length dependency and prediction of ventricular arrhythmias during human epicardial sock mapping

The re-entry vulnerability index (RVI) is an activation-repolarization marker recently proposed to predict sites of ventricular tachycardia (VT) initiation. RVI is inversely related to the probability of establishing a re-entry. The aim of this study was to characterize the CL dependency of RVI, assess different methods for CL-dependency corrections and test the capability of RVI to predict ventricular arrhythmias. Twenty-four subjects underwent whole heart epicardial mapping using a multi-electrode sock enabling the recording of 240 unipolar electrograms. Ventricular pacing was delivered at CLs decreasing from 600 to 350 ms in steps of 50 ms. In a separate study, 1 patient went into VT during steady state pacing. Predisposition to VT was assessed by using the 10th percentile RVI, termed global RVI. The results show that own to CL dependency of local repolarization, there was a strong positive association between RVI and CL. Local repolarization detrending and correction with the Bazett's formula eliminated the CL dependency, while a weak association was found after correction with the Fredericia's formula. In the patient who developed VT, global RVI was significantly lower than in the patients who did not develop VT. Corrections for CL dependency enhanced these differences. In conclusion, de-trending and Bazett's corrections effectively compensated for the CL dependency of RVI and global RVI may reveal predisposition to ventricular arrhythmias. Further analysis is necessary to establish the role of RVI for risk stratification