Altered cortical activation patterns associated with baroreflex unloading following 24 h of physical deconditioning

Cardiovascular arousal is associated with patterned cortical activity changes. Head-down-tilt bed rest (HDBR) dimishes the baroreflex-mediated cardiac control. The present study tested the hypothesis that HDBR deconditioning would modify the forebrain organization for heart rate (HR) control during baroreflex unloading. Heart rate variability (HRV), blood pressure and plasma hormones were analysed at rest, whereas HR and cortical autonomic activation patterns (functional magnetic resonance imaging) were measured during graded and randomly assigned lower body negative pressure treatments (LBNP, -15 and -35 mmHg) both before (Pre) and after (Post) a 24 h HDBR protocol (study 1; n= 8). An additional group was tested before and following diuretic-induced hypovolaemia (study 2; n= 9; spironolactone, 100 mg day-1 for 3 days) that mimicked the plasma volume lost during HDBR (-15% in both studies; P \u3c 0.05). Head-down bed rest with hypovolaemia did not affect baseline HR, mean arterial pressure, HRV or plasma catecholamines. Head-down bed rest augmented the LBNP-induced HR response (P \u3c 0.05), and this was associated with bed-rest-induced development of the following changes: (i) enhanced activation within the genual anterior cingulate cortex and the right anterior insular cortex; and (ii) deactivation patterns within the subgenual regions of the anterior cingulate cortex. Diuretic treatment (without HDBR) did not affect baseline HR and mean arterial pressure, but did reduce resting HRV and elevated circulating noradrenaline and plasma renin activity (P \u3c 0.05). The greater HR response to LBNP following diuretic (P \u3c 0.05) was associated with diminished activation of the right anterior insula. Our findings indicate that 24 h of HDBR minimized the impact of diuretic treatment on baseline autonomic and cardiovascular variables. The findings also indicate that despite the similar augmentation of HR responses to LBNP and despite similar pre-intervention cortical activation patterns, HDBR and diuretic treatment produced different effects on the cortical responses, with HDBR affecting anterior cingulate cortex and right insula regions, whereas diuretic treatment affected primarily the right insula alone, but in a direction that was opposite to HDBR. The data indicate that physical deconditioning can induce rapid functional changes within the cortical circuitry associated with baroreflex unloading, changes that are distinct from diuretic-induced hypovolaemia. The results suggest that physical activity patterns exert a rapid and notable impact on the cortical circuitry associated with cardiovascular control. © 2012 The Physiological Society

Impaired automatic but intact volitional inhibition in primary tic disorders

The defining character of tics is that they can be transiently suppressed by volitional effort of will, and at a behavioural level this has led to the concept that tics result from a failure of inhibition. However, this logic conflates the mechanism responsible for the production of tics with that used in suppressing them. Volitional inhibition of motor output could be increased to prevent the tic from reaching the threshold for expression, although this has been extensively investigated with conflicting results. Alternatively, automatic inhibition could prevent the initial excitation of the striatal tic focus-a hypothesis we have previously introduced. To reconcile these competing hypotheses, we examined different types of motor inhibition in a group of 19 patients with primary tic disorders and 15 healthy volunteers. We probed proactive and reactive inhibition using the conditional stop-signal task, and applied transcranial magnetic stimulation to the motor cortex, to assess movement preparation and execution. We assessed automatic motor inhibition with the masked priming task. We found that volitional movement preparation, execution and inhibition (proactive and reactive) were not impaired in tic disorders. We speculate that these mechanisms are recruited during volitional tic suppression, and that they prevent expression of the tic by inhibiting the nascent excitation released by the tic generator. In contrast, automatic inhibition was abnormal/impaired in patients with tic disorders. In the masked priming task, positive and negative compatibility effects were found for healthy controls, whereas patients with tics exhibited strong positive compatibility effects, but no negative compatibility effect indicative of impaired automatic inhibition. Patients also made more errors on the masked priming task than healthy control subjects and the types of errors were consistent with impaired automatic inhibition. Errors associated with impaired automatic inhibition were positively correlated with tic severity. We conclude that voluntary movement preparation/generation and volitional inhibition are normal in tic disorders, whereas automatic inhibition is impaired-a deficit that correlated with tic severity and thus may constitute a potential mechanism by which tics are generated

Impaired automatic but intact volitional inhibition in primary tic disorders

The defining character of tics is that they can be transiently suppressed by volitional effort of will, and at a behavioural level this has led to the concept that tics result from a failure of inhibition. However, this logic conflates the mechanism responsible for the production of tics with that used in suppressing them. Volitional inhibition of motor output could be increased to prevent the tic from reaching the threshold for expression, although this has been extensively investigated with conflicting results. Alternatively, automatic inhibition could prevent the initial excitation of the striatal tic focus—a hypothesis we have previously introduced. To reconcile these competing hypotheses, we examined different types of motor inhibition in a group of 19 patients with primary tic disorders and 15 healthy volunteers. We probed proactive and reactive inhibition using the conditional stop-signal task, and applied transcranial magnetic stimulation to the motor cortex, to assess movement preparation and execution. We assessed automatic motor inhibition with the masked priming task. We found that volitional movement preparation, execution and inhibition (proactive and reactive) were not impaired in tic disorders. We speculate that these mechanisms are recruited during volitional tic suppression, and that they prevent expression of the tic by inhibiting the nascent excitation released by the tic generator. In contrast, automatic inhibition was abnormal/impaired in patients with tic disorders. In the masked priming task, positive and negative compatibility effects were found for healthy controls, whereas patients with tics exhibited strong positive compatibility effects, but no negative compatibility effect indicative of impaired automatic inhibition. Patients also made more errors on the masked priming task than healthy control subjects and the types of errors were consistent with impaired automatic inhibition. Errors associated with impaired automatic inhibition were positively correlated with tic severity. We conclude that voluntary movement preparation/generation and volitional inhibition are normal in tic disorders, whereas automatic inhibition is impaired—a deficit that correlated with tic severity and thus may constitute a potential mechanism by which tics are generated

Blood pressure variability and cardiovascular risk in the PROspective study of pravastatin in the elderly at risk (PROSPER)

Variability in blood pressure predicts cardiovascular disease in young- and middle-aged subjects, but relevant data for older individuals are sparse. We analysed data from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study of 5804 participants aged 70–82 years with a history of, or risk factors for cardiovascular disease. Visit-to-visit variability in blood pressure (standard deviation) was determined using a minimum of five measurements over 1 year; an inception cohort of 4819 subjects had subsequent in-trial 3 years follow-up; longer-term follow-up (mean 7.1 years) was available for 1808 subjects. Higher systolic blood pressure variability independently predicted long-term follow-up vascular and total mortality (hazard ratio per 5 mmHg increase in standard deviation of systolic blood pressure = 1.2, 95% confidence interval 1.1–1.4; hazard ratio 1.1, 95% confidence interval 1.1–1.2, respectively). Variability in diastolic blood pressure associated with increased risk for coronary events (hazard ratio 1.5, 95% confidence interval 1.2–1.8 for each 5 mmHg increase), heart failure hospitalisation (hazard ratio 1.4, 95% confidence interval 1.1–1.8) and vascular (hazard ratio 1.4, 95% confidence interval 1.1–1.7) and total mortality (hazard ratio 1.3, 95% confidence interval 1.1–1.5), all in long-term follow-up. Pulse pressure variability was associated with increased stroke risk (hazard ratio 1.2, 95% confidence interval 1.0–1.4 for each 5 mmHg increase), vascular mortality (hazard ratio 1.2, 95% confidence interval 1.0–1.3) and total mortality (hazard ratio 1.1, 95% confidence interval 1.0–1.2), all in long-term follow-up. All associations were independent of respective mean blood pressure levels, age, gender, in-trial treatment group (pravastatin or placebo) and prior vascular disease and cardiovascular disease risk factors. Our observations suggest variability in diastolic blood pressure is more strongly associated with vascular or total mortality than is systolic pressure variability in older high-risk subjects

Prevention is better than cure, but...: Preventive medication as a risk to ordinariness?

Preventive health remains at the forefront of public health concerns; recent initiatives, such as the NHS health check, may lead to recommendations for medication in response to the identification of 'at risk' individuals. Little is known about lay views of preventive medication. This paper uses the case of aspirin as a prophylactic against heart disease to explore views among people invited to screening for a trial investigating the efficacy of such an approach. Qualitative interviews (N=46) and focus groups (N=5, participants 31) revealed dilemmas about preventive medication in the form of clashes between norms: first, in general terms, assumptions about the benefit of prevention were complicated by dislike of medication; second, the individual duty to engage in prevention was complicated by the need not to be over involved with one's own health; third, the potential appeal of this alternative approach to health promotion was complicated by unease about the implications of encouraging irresponsible behaviour among others. Though respondents made different decisions about using the drug, they reported very similar ways of trying to resolve these conflicts, drawing upon concepts of necessity and legitimisation and the special ordinariness of the particular dru

Genetic basis of Campylobacter colonisation in the broiler chicken and its impact on intestinal health following natural field exposure

Campylobacter is the leading bacterial cause of foodborne diarrheal illness in humans and source attribution studies unequivocally identify handling or consumption of poultry meat as a key risk factor. Campylobacter colonizes the avian intestines in high numbers and rapidly spreads within flocks. A need therefore exists to devise strategies to reduce Campylobacter populations in poultry flocks. There has been a great deal of research aiming to understand the epidemiology and transmission characteristics of Campylobacter in poultry as a means to reduce carriage rates in poultry and reduce infection in humans. One potential strategy for control is the genetic selection of poultry for increased resistance to colonization by Campylobacter. The potential for genetic control of colonization has been demonstrated in inbred populations following experimental challenge with Campylobacter where quantitative trait loci associated with resistance have been identified. Currently in the literature there is no information of the genetic basis of Campylobacter colonization in commercial broiler lines and it is unknown whether these QTL are found in commercial broiler lines. The aim of this study was to estimate genetic parameters associated with Campylobacter load and genetic correlations with gut health and production traits following natural exposure of broiler chickens to Campylobacter. The results from the analysis show a low but significant heritability estimate (0.095 ± 0.037) for Campylobacter load which indicates a limited genetic basis and that non-genetic factors have a greater influence on the level of Campylobacter found in the broiler chicken. Furthermore, through examination of macroscopic intestinal health and absorptive capacity, our study indicated that Campylobacter has no detrimental effects on intestinal health and bird growth following natural exposure in the broiler line under study. These data indicate that whilst there is a genetic component to Campylobacter colonization worthy of further investigation, there is a large proportion of phenotypic variance under the influence of non-genetic effects. As such the control of Campylobacter will require understanding and manipulation of non-genetic host and environmental factors

Polyphenols: A concise overview on the chemistry, occurrence, and human health

This review gives an updated picture of each class of phenolic compounds and their properties. The most common classification implies the subdivision of phenolics in two main groups: flavonoids (e.g., anthocyanins, flavanols, flavanones, flavonols, flavonones, and isoflavones) and non-flavonoids (e.g., phenolic acids, xanthones, stilbens, lignans, and tannins) polyphenols. The great interest in polyphenols is associated with their high potential application for food preservation and for therapeutic beneficial use. The relationship between polyphenol intake and human health has been exploited with special reference to cardiovascular diseases, hypertension, diabetes, metabolic syndrome, obesity, and cancer. The use of current existing databases of bioactive compounds including polyphenols is described as key tools for human health research.info:eu-repo/semantics/publishedVersio

Pragmatic trials of non-NHS interventions: experiences from a Randomised Controlled Trial of the Strengthening Families 10-14 UK Programme (SFP10-14 UK)

Background: Pragmatic trials of public health interventions outside the NHS are relatively scarce, much needed and face particular challenges. These include funding, of intervention costs in particular; trial implementation in professional and organisational cultures unused to randomised trial procedures, including randomisation, maintaining the counterfactual, recruitment; and relevance of findings for and translation into policy and practice. Objectives: The current NPRI funded trial of SFP 10-14 UK is presented as a case study to discuss these issues, solutions and remaining barriers. The SFP 10-14 UK programme aims to strengthen areas of family life that protect against substance misuse, for example, parenting, communication, and young people’s resilience skills. The SFP 10-14 UK is being delivered by statutory and voluntary agencies in six local authority areas across Wales, and is offered to mixed groups comprised of families from the general population, and families who may experience/present challenges within a group setting. Methods: The trial aims to recruit 748 families, 374 of whom will be randomised to receive the usual services available to families within their local area. 374 families will receive the SFP 10-14 UK in addition to usual care. Families are identified by staff employed within the statutory services and voluntary sectors and referred to embedded research staff for recruitment. Results: Challenges encountered related to a lack of awareness of the randomised trial as a research paradigm among staff and key referring agencies, related concerns about the ethics of randomisation and the maintenance of the counterfactual among the usual care group, and challenges regarding the maintenance of recruitment and intervention fidelity. Whilst a challenge in itself, partnership working with delivery agencies, programme trainers, and the Welsh Assembly Government at all stages of the development, funding and conduct of the trial has proved an important strategy to overcome these issues. Conclusions: This trial seeks to generate evidence on the effectiveness and cost effectiveness of the SFP10-14 UK which is of direct relevance to policy makers, commissioners and practitioners. The trial highlights that strategic partnership working, the winning of ‘hearts and minds’ regarding the ethics and operationalisation of randomisation, and maintaining the balance between internal and external validity are key areas of focus for the successful conduct of pragmatic trials in non-NHS settings. The lessons learnt from its implementation will be important for future multi-sector/agency policy trials and for role out of the intervention if found to be efficacious