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

A systematic review of interventions in primary care to improve health literacy for chronic disease behavioral risk factors

Background: To evaluate the effectiveness of interventions used in primary care to improve health literacy for change in smoking, nutrition, alcohol, physical activity and weight (SNAPW). Methods: A systematic review of intervention studies that included outcomes for health literacy and SNAPW behavioral risk behaviors implemented in primary care settings. We searched the Cochrane Library, Johanna Briggs Institute, Medline, Embase, CINAHL, Psychinfo, Web of Science, Scopus, APAIS, Australasian Medical Index, Google Scholar, Community of Science and four targeted journals (Patient Education and Counseling, Health Education and Behaviour, American Journal of Preventive Medicine and Preventive Medicine). Study inclusion criteria: Adults over 18 years; undertaken in a primary care setting within an Organisation for Economic Co-operation and Development (OECD) country; interventions with at least one measure of health literacy and promoting positive change in smoking, nutrition, alcohol, physical activity and/or weight; measure at least one outcome associated with health literacy and report a SNAPW outcome; and experimental and quasi-experimental studies, cohort, observational and controlled and non-controlled before and after studies. Papers were assessed and screened by two researchers (JT, AW) and uncertain or excluded studies were reviewed by a third researcher (MH). Data were extracted from the included studies by two researchers (JT, AW). Effectiveness studies were quality assessed. A typology of interventions was thematically derived from the studies by grouping the SNAPW interventions into six broad categories: individual motivational interviewing and counseling; group education; multiple interventions (combination of interventions); written materials; telephone coaching or counseling; and computer or web based interventions. Interventions were classified by intensity of contact with the subjects (High ≥ 8 points of contact/hours; Moderate \u3e3 and \u3c8; Low ≤ 3 points of contact hours) and setting (primary health, community or other). Studies were analyzed by intervention category and whether significant positive changes in SNAPW and health literacy outcomes were reported. Results: 52 studies were included. Many different intervention types and settings were associated with change in health literacy (73% of all studies) and change in SNAPW (75% of studies). More low intensity interventions reported significant positive outcomes for SNAPW (43% of studies) compared with high intensity interventions (33% of studies). More interventions in primary health care than the community were effective in supporting smoking cessation whereas the reverse was true for diet and physical activity interventions. Conclusion: Group and individual interventions of varying intensity in primary health care and community settings are useful in supporting sustained change in health literacy for change in behavioral risk factors. Certain aspects of risk behavior may be better handled in clinical settings while others more effectively in the community. Our findings have implications for the design of programs

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

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

Répercussions biopsychosociales du Sida et pistes d’intervention et de recherche

Le syndrome d'immunodéficience acquise (SIDA) constitue un problème mondial de santé publique d'une ampleur exceptionnelle. Son impact est considérable sur plusieurs plans : individuel, social, économique, démographique et culturel. Les écrits relatifs au SIDA démontrent bien l'impact émotionnel des pertes occasionnées par cette maladie fatale sur les personnes atteintes. Celles-ci éprouvent des sentiments intenses d'anxiété, de peur, de colère, d'impuissance et de désespoir. À cette détresse psychologique s'ajoute l'isolement des victimes. La réaction négative entretenue au sein de la société à l'égard du SIDA contribue à discriminer et stigmatiser les victimes de cette maladie. Le SIDA est en quelque sorte un drame personnel et un effondrement de la vie familiale et sociale. Les répercussions psychosociales de cette maladie exigent des stratégies d'intervention et de recherche appropriées aux divers problèmes soulevés par le syndrome.The acquired immunodeficiency syndrome (AIDS) is a world wide health problem of exceptional magnitude with considerable effect in many areas : individual, social, economic, demographic and cultural. Current literature clearly indicates the emotional impact of the losses occasionnée by those suffering from this fatal disease. There include strong anxiety, fear, anger powerlessness and hopelessness. To this psychological distress is added isolation of AIDS victims. The negative reaction of society contributes to discrimination and stigmatization of these victims. AIDS may be seen as a personnal tragedy which often spells the collapse of family life. The psychosocial repercussions of this disease require intervention and further research with respect to the many unresolved problems generated by this syndrome

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

Theoretical assessment of a repolarization time marker based on the intracardiac bipolar electrogram

The spatio-temporal organization of cardiac repolarization modulates the vulnerability to dangerous ventricular arrhythmias. Methodologies that provide accurate assessment of cardiac repolarization are of primary importance for a better understanding of cardiac electrophysiology and represent a potentially useful tool for clinical applications. The most commonly used repolarization time (RT) marker from extracellular recordings is derived from the unipolar electrogram (UEG). However, far field potentials and remote activity may in certain conditions bias this marker. In this paper, a RT marker based on the bipolar electrogram (BEG) is proposed. An analytical expression of the BEG based on a simple model of the cardiac extracellular potential is derived. According to the proposed analytical framework the BEG exhibits a repolarization wave whose extremum (maximum or minimum) corresponds to the average of the local RTs at the two electrodes of the bipole. The amplitude of this extremum is a function of the steepness of phase 3 of the action potentials, inter-electrode distance, conduction velocity and direction of wave-back propagation. A simulation study based on this analytical framework showed that for noisy to good signal quality (SNR of the UEG ≥ 10 dB), and for a typical inter-electrode distance of 2 mm, conduction velocity between 0.2 and 0.6 m/s, and an angle between conduction direction and the inter-electrode axis ≤ π/4, the median absolute error was lower than 6.8 ms while the median linear correlation between estimated and theoretical RT was higher than 0.91. Examples of RT derived from BEG recorded in a structurally normal heart in both the right and left ventricles demonstrate that the proposed procedure is feasible in human in-vivo studies

The Role of Whey Acidic Protein Four-Disulfide-Core Proteins in Respiratory Health and Disease

Abstract Members of the whey acidic protein (WAP) or WAP four-disulfide-core (WFDC) family of proteins are a relatively under-explored family of low molecular weight proteins. The two most prominent WFDC proteins, secretory leukocyte protease inhibitor (SLPI) and elafin (or the precursor, trappin-2), have been shown to possess multiple functions including anti-protease, anti-bacterial, anti-viral and anti-inflammatory properties. It is therefore of no surprise that both SLPI and elafin/trappin-2 have been developed as potential therapeutics. Given the abundance of SLPI and elafin/trappin-2 in the human lung, most work in the area of WFDC research has focused on the role of WFDC proteins in protecting the lung from proteolytic attack. In this review, we will outline the current evidence regarding the expanding role of WFDC protein function with a focus on WFDC activity in lung disease as well as emerging data regarding the function of some of the more recently described WFDC proteins.</jats:p