The role of epigenetics in cardiovascular health and ageing: A focus on physical activity and nutrition

The cardiovascular system is responsible for transport of blood and nutrients to tissues, and is pivotal to the physiological health and longevity. Epigenetic modification is a natural, age-associated process resulting in highly contextualised gene expression with clear implications for cell differentiation and disease onset. Biological/epigenetic age is independent of chronological age, constituting a highly reflective snapshot of an individual\u27s overall health. Accelerated vascular ageing is of major concern, effectively lowering disease threshold. Age-related chronic illness involves a complex interplay between many biological processes and is modulated by non-modifiable and modifiable risk factors. These alter the static genome by a number of epigenetic mechanisms, which change gene expression in an age and lifestyle dependent manner. This \u27epigenetic drift\u27 impacts health and contributes to the etiology of chronic illness. Lifestyle factors may cause acceleration of this epigenetic "clock", pre-disposing individuals to cardiovascular disease. Nutrition and physical activity are modifiable lifestyle choices, synergistically contributing to cardiovascular health. They represent a powerful potential epigenetic intervention point for effective cardiovascular protective and management strategies. Thus, together with traditional risk factors, monitoring the epigenetic signature of ageing may prove beneficial for tailoring lifestyle to fit biology - supporting the increasingly popular concept of "ageing well"

Edoxaban vs. warfarin in patients with atrial fibrillation on amiodarone: a subgroup analysis of the ENGAGE AF-TIMI 48 trial

Background In the ENGAGE AF-TIMI 48 trial, the higher-dose edoxaban (HDE) regimen had a similar incidence of ischaemic stroke compared with warfarin, whereas a higher incidence was observed with the lower-dose regimen (LDE). Amiodarone increases edoxaban plasma levels via P-glycoprotein inhibition. The current pre-specified exploratory analysis was performed to determine the effect of amiodarone on the relative efficacy and safety profile of edoxaban. Methods and results At randomization, 2492 patients (11.8%) were receiving amiodarone. The primary efficacy endpoint of stroke or systemic embolic event was significantly lower with LDE compared with warfarin in amiodarone treated patients vs. patients not on amiodarone (hazard ratio [HR] 0.60, 95% confidence intervals [CIs] 0.36-0.99 and HR 1.20, 95% CI 1.03-1.40, respectively; P interaction <0.01). In patients randomized to HDE, no such interaction for efficacy was observed (HR 0.73, 95% CI 0.46-1.17 vs. HR 0.89, 95% CI 0.75-1.05, P interaction = 0.446). Major bleeding was similar in patients on LDE (HR 0.35, 95% CI 0.21-0.59 vs. HR 0.53, 95% CI 0.46-0.61, P interaction = 0.131) and HDE (HR 0.94, 95% CI 0.65-1.38 vs. HR 0.79, 95% CI 0.69-0.90, P interaction = 0.392) when compared with warfarin, independent of amiodarone use. Conclusions Patients randomized to the LDE treated with amiodarone at the time of randomization demonstrated a significant reduction in ischaemic events vs. warfarin when compared with those not on amiodarone, while preserving a favourable bleeding profile. In contrast, amiodarone had no effect on the relative efficacy and safety of HD

Capability, opportunity, and motivation to enact hygienic practices in the early stages of the COVID‐19 outbreak in the United Kingdom

Objectives The COVID‐19 pandemic is one of the greatest global health threats facing humanity in recent memory. This study aimed to explore influences on hygienic practices, a set of key transmission behaviours, in relation to the Capability, Opportunity, Motivation‐Behaviour (COM‐B) model of behaviour change (Michie et al., 2011). Design Data from the first wave of a longitudinal survey study were used, launched in the early stages of the UK COVID‐19 pandemic. Methods Participants were 2025 adults aged 18 and older, representative of the UK population, recruited by a survey company from a panel of research participants. Participants self‐reported motivation, capability, and opportunity to enact hygienic practices during the COVID‐19 outbreak. Results Using regression models, we found that all three COM‐B components significantly predicted good hygienic practices, with motivation having the greatest influence on behaviour. Breaking this down further, the subscales psychological capability, social opportunity, and reflective motivation positively influenced behaviour. Reflective motivation was largely driving behaviour, with those highest in reflective motivation scoring 51% more on the measure of hygienic practices compared with those with the lowest scores. Conclusions Our findings have clear implications for the design of behaviour change interventions to promote hygienic practices. Interventions should focus on increasing and maintaining motivation to act and include elements that promote and maintain social support and knowledge of COVID‐19 transmission. Groups in particular need of targeting for interventions to increase hygienic practices are males and those living in cities and suburbs

Scenario of Accelerating Universe from the Phenomenological \Lambda- Models

Dark matter, the major component of the matter content of the Universe, played a significant role at early stages during structure formation. But at present the Universe is dark energy dominated as well as accelerating. Here, the presence of dark energy has been established by including a time-dependent $\Lambda$ term in the Einstein's field equations. This model is compatible with the idea of an accelerating Universe so far as the value of the deceleration parameter is concerned. Possibility of a change in sign of the deceleration parameter is also discussed. The impact of considering the speed of light as variable in the field equations has also been investigated by using a well known time-dependent $\Lambda$ model.Comment: Latex, 9 pages, Major change

Moral courage in the workplace: moving to and from the desire and decision to act

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72135/1/j.1467-8608.2007.00484.x.pd

Configuration-interaction calculations of positron binding to zinc and cadmium

The configuration-interaction method is applied to the study of positronic zinc (e+Zn) and positronic cadmium (e+Cd). The estimated binding energies and annihilation rates were 0.00373 hartree and 0.42&times;109 sec-1 for e+Zn and 0.006 10 hartree and 0.56&times;109 sec-1 for e+Cd. The low-energy elastic cross section and Zeff were estimated from a model potential that was tuned to the binding energies and annihilation rates. Since the scattering lengths were positive (14.5a0 for Zn and 11.6a0 for Cd) the differential cross sections are larger at backward angles than at forward angles just above threshold. The possibilities of measuring differential cross sections to confirm positron binding to these atoms is discussed

A Staphylococcus aureus ypfP mutant with strongly reduced lipoteichoic acid (LTA) content: LTA governs bacterial surface properties and autolysin activity

Many Gram-positive bacteria produce lipoteichoic acid (LTA) polymers whose physiological roles have remained a matter of debate because of the lack of LTA-deficient mutants. The ypfP gene responsible for biosynthesis of a glycolipid found in LTA was deleted in Staphylococcus aureus SA113, causing 87% reduction of the LTA content. Mass spectrometry and nuclear magnetic resonance spectroscopy revealed that the mutant LTA contained a diacylglycerol anchor instead of the glycolipid, whereas the remaining part was similar to the wild-type polymer except that it was shorter. The LTA mutant strain revealed no major changes in patterns of cell wall proteins or autolytic enzymes compared with the parental strain indicating that LTA may be less important in S. aureus protein attachment than previously thought. However, the autolytic activity of the mutant was strongly reduced demonstrating a role of LTA in controlling autolysin activity. Moreover, the hydrophobicity of the LTA mutant was altered and its ability to form biofilms on plastic was completely abrogated indicating a profound impact of LTA on physicochemical properties of bacterial surfaces. We propose to consider LTA and its biosynthetic enzymes as targets for new antibiofilm strategies

The complex and spatially diverse patterns of hydrological droughts across Europe

This study presents a new data set of gauged streamflow (N = 3,224) for Europe spanning the period 1962–2017. The Monthly Streamflow of Europe Dataset (MSED) is freely available at http://msed.csic.es/. Based on this data set, changes in the characteristics of hydrological drought (i.e., frequency, duration, and severity) were assessed for different regions of Europe. Due to the density of the database, it is possible to delimit spatial patterns in hydrological droughts trend with the greatest detail available to date. Results reveal bidirectional changes in monthly streamflow, with negative changes predominating over central and southern Europe, while positive trends dominate over northern Europe. Temporally, two dominant patterns were noted. The first pattern corresponds to a consistent downward trend in all months, evident for southern Europe. A second pattern was noted over central and northern Europe and western France, with a predominant negative trend during warm months and a positive trend in cold months. For hydrological drought events, results suggest a positive trend toward more frequent and severe droughts in southern and central Europe and conversely a negative trend over northern Europe. This study emphasizes that hydrological droughts show complex spatial patterns across Europe over the past six decades, implying that hydrological drought behavior in Europe has a regional character. Accordingly it is challenging to adopt “efficient” strategies and policies to monitor and mitigate drought impacts at the continental level

The relationship between the perception of distributed leadership in secondary schools and teachers' and teacher leaders' job satisfaction and organizational commitment

This study investigates the relation between distributed leadership, the cohesion of the leadership team, participative decision-making, context variables, and the organizational commitment and job satisfaction of teachers and teacher leaders. A questionnaire was administered to teachers and teacher leaders (n=1770) from 46 large secondary schools. Multiple regression analyses and path analyses revealed that the study variables explained significant variance in organizational commitment. The degree of explained variance for job satisfaction was considerably lower compared to organizational commitment. Most striking was that the cohesion of the leadership team and the amount of leadership support was strongly related to organizational commitment, and indirectly to job satisfaction. Decentralization of leadership functions was weakly related to organizational commitment and job satisfaction

EFFECT OF CORTISOL TREATMENT ON HORMONAL RELATIONSHIPS IN CONGENITAL ADRENAL HYPERPLASIA

The temporal relationship between administration of cortisol and serum 17Α-hydroxyprogesterone was investigated in five patients aged 9-19 years with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. There was marked variability in the 17Α-hydroxyprogesterone response (determined hourly for 24 h) of individual patients to administration of cortisol. Mean concentration was less than 0.030 Μmol/l in one patient but 0.519Μ mol/l in another. Levels were higher in all patients while off treatment, and were greatest in those with salt-losing adrenal hyperplasia. Growth hormone secretion was not suppressed by treatment with cortisol. Withdrawal of cortisol for 3 days resulted in a significant decrease in the mean serum FSH/LH ratio and a rise in serum testosterone in all subjects. Episodic release of gonadotrophins persisted in the adolescent patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75713/1/j.1365-2265.1977.tb02002.x.pd