Patent Foramen Ovale Closure: State of the Art

Patent foramen ovale (PFO) is a common abnormality affecting between 20% and 34% of the adult population. For most people, it is a benign finding; however, in some people, the PFO can open widely to enable paradoxical embolus to transit from the venous to arterial circulation, which is associated with stroke and systemic embolisation. Percutaneous closure of the PFO in patients with cryptogenic stroke has been undertaken for a number of years, and a number of purpose-specific septal occluders have been marketed. Recent randomised control trials have demonstrated that closure of PFO in patients with cryptogenic stroke is associated with reduced rates of recurrent stroke. After a brief overview of the anatomy of a PFO, this article considers the evidence for PFO closure in cryptogenic stroke. The article also addresses other potential indications for closure, including systemic arterial embolisation, decompression sickness, platypnoea–orthodeoxia syndrome and migraine with aura. The article lays out the pre-procedural investigations and preparation for the procedure. Finally, the article gives an overview of the procedure itself, including discussion of closure devices

Genetic Analysis of the Neurosteroid Deoxycorticosterone and Its Relation to Alcohol Phenotypes: Identification of QTLs and Downstream Gene Regulation

Deoxycorticosterone (DOC) is an endogenous neurosteroid found in brain and serum, precursor of the GABAergic neuroactive steroid (3α,5α)-3,21-dihydroxypregnan-20-one (tetrahydrodeoxycorticosterone, THDOC) and the glucocorticoid corticosterone. These steroids are elevated following stress or ethanol administration, contribute to ethanol sensitivity, and their elevation is blunted in ethanol dependence.To systematically define the genetic basis, regulation, and behavioral significance of DOC levels in plasma and cerebral cortex we examined such levels across 47 young adult males from C57BL/6J (B6)×DBA/2J (D2) (BXD) mouse strains for quantitative trait loci (QTL) and bioinformatics analyses of behavior and gene regulation. Mice were injected with saline or 0.075 mg/kg dexamethasone sodium salt at 8:00 am and were sacrificed 6 hours later. DOC levels were measured by radioimmunoassay. Basal cerebral cortical DOC levels ranged between 1.4 and 12.2 ng/g (8.7-fold variation, p<0.0001) with a heritability of ∼0.37. Basal plasma DOC levels ranged between 2.8 and 12.1 ng/ml (4.3-fold variation, p<0.0001) with heritability of ∼0.32. QTLs for basal DOC levels were identified on chromosomes 4 (cerebral cortex) and 14 (plasma). Dexamethasone-induced changes in DOC levels showed a 4.4-fold variation in cerebral cortex and a 4.1-fold variation in plasma, but no QTLs were identified. DOC levels across BXD strains were further shown to be co-regulated with networks of genes linked to neuronal, immune, and endocrine function. DOC levels and its responses to dexamethasone were associated with several behavioral measures of ethanol sensitivity previously determined across the BXD strains by multiple laboratories.Both basal and dexamethasone-suppressed DOC levels are positively correlated with ethanol sensitivity suggesting that the neurosteroid DOC may be a putative biomarker of alcohol phenotypes. DOC levels were also strongly correlated with networks of genes associated with neuronal function, innate immune pathways, and steroid metabolism, likely linked to behavioral phenotypes

Percutaneous Transcatheter Closure of Post-infarction Ventricular Septal Defect: An Alternative to Surgical Intervention

Post-infarction ventricular septal defect is a mechanical complication of acute MI. The incidence of this complication is low in the primary percutaneous coronary intervention era. However, the associated mortality is very high at 94% with medical management alone. Open surgical repair or percutaneous transcatheter closure still has an in-hospital mortality >40%. Retrospective comparisons between both closure methods are limited by observation and selection bias. This review addresses the assessment and optimisation of patients prior to repair, the optimal timing of repair, and the limitations in current data. The review considers techniques for percutaneous closure, and finally considers the path that future research should take to improve outcomes for patients

Pellino-1 Regulates the Responses of the Airway to Viral Infection

Exposure to respiratory pathogens is a leading cause of exacerbations of airway diseases such as asthma and chronic obstructive pulmonary disease (COPD). Pellino-1 is an E3 ubiquitin ligase known to regulate virally-induced inflammation. We wished to determine the role of Pellino-1 in the host response to respiratory viruses in health and disease. Pellino-1 expression was examined in bronchial sections from patients with GOLD stage two COPD and healthy controls. Primary bronchial epithelial cells (PBECs) in which Pellino-1 expression had been knocked down were extracellularly challenged with the TLR3 agonist poly(I:C). C57BL/6 Peli1-/- mice and wild type littermates were subjected to intranasal infection with clinically-relevant respiratory viruses: rhinovirus (RV1B) and influenza A. We found that Pellino-1 is expressed in the airways of normal subjects and those with COPD, and that Pellino-1 regulates TLR3 signaling and responses to airways viruses. In particular we observed that knockout of Pellino-1 in the murine lung resulted in increased production of proinflammatory cytokines IL-6 and TNFα upon viral infection, accompanied by enhanced recruitment of immune cells to the airways, without any change in viral replication. Pellino-1 therefore regulates inflammatory airway responses without altering replication of respiratory viruses.</p

Metabolic manipulation in chronic heart failure: study protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Heart failure is a major cause of morbidity and mortality in society. Current medical therapy centres on neurohormonal modulation with angiotensin converting enzyme inhibitors and β-blockers. There is growing evidence for the use of metabolic manipulating agents as adjunctive therapy in patients with heart failure. We aim to determine the effect of perhexiline on cardiac energetics and alterations in substrate utilisation in patients with non-ischaemic dilated cardiomyopathy.</p> <p>Methods</p> <p>A multi-centre, prospective, randomised double-blind, placebo-controlled trial of 50 subjects with non-ischaemic dilated cardiomyopathy recruited from University Hospital Birmingham NHS Foundation Trust and Cardiff and Vale NHS Trust. Baseline investigations include magnetic resonance spectroscopy to assess cardiac energetic status, echocardiography to assess left ventricular function and assessment of symptomatic status. Subjects are then randomised to receive 200 mg perhexiline maleate or placebo daily for 4 weeks with serum drug level monitoring. All baseline investigations will be repeated at the end of the treatment period. A subgroup of patients will undergo invasive investigations with right and left heart catheterisation to calculate respiratory quotient, and mechanical efficiency. The primary endpoint is an improvement in the phosphocreatine to adenosine triphosphate ratio at 4 weeks. Secondary end points are: i) respiratory quotient; ii) mechanical efficiency; iii) change in left ventricular (LV) function.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00841139">NCT00841139</a></p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN2887836">ISRCTN2887836</a></p

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24&nbsp;months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500&nbsp;steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30&nbsp;minutes spent performing activities ≥500&nbsp;counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24&nbsp;months), both the number of steps per day (per 500&nbsp;steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500&nbsp;counts per minute (per 30&nbsp;minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score &gt;10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

Using formative research to develop the healthy eating component of the CHANGE! school-based curriculum intervention

Background: Childhood obesity is a significant public health concern. Many intervention studies have attempted to combat childhood obesity, often in the absence of formative or preparatory work. This study describes the healthy eating component of the formative phase of the Children’s Health Activity and Nutrition: Get Educated! (CHANGE!) project. The aim of the present study was to gather qualitative focus group and interview data regarding healthy eating particularly in relation to enabling and influencing factors, barriers and knowledge in children and adults (parents and teachers) from schools within the CHANGE! programme to provide populationspecific evidence to inform the subsequent intervention design. Methods: Semi-structured focus group interviews were conducted with children, parents and teachers across 11 primary schools in the Wigan borough of North West England. Sixty children (N = 24 boys), 33 parents (N = 4 male) and 10 teachers (N = 4 male) participated in the study. Interview questions were structured around the PRECEDE phases of the PRECEDE-PROCEED model. Interviews were transcribed verbatim and analysed using the pen-profiling technique. Results: The pen-profiles revealed that children’s knowledge of healthy eating was generally good, specifically many children were aware that fruit and vegetable consumption was ‘healthy’ (N = 46). Adults’ knowledge was also good, including restricting fatty foods, promoting fruit and vegetable intake, and maintaining a balanced diet. The important role parents play in children’s eating behaviours and food intake was evident. The emerging themes relating to barriers to healthy eating showed that external drivers such as advertising, the preferred sensory experience of “unhealthy” foods, and food being used as a reward may play a role in preventing healthy eating. Conclusions: Data suggest that; knowledge related to diet composition was not a barrier per se to healthy eating, and education showing how to translate knowledge into behavior or action is required. The key themes that emerged through the focus groups and pen-profiling data analysis technique will be used to inform and tailor the healthy eating component of the CHANGE! intervention study. Trial registration: Current Controlled Trials ISRCTN03863885 Keywords: Nutrition, Childhood obesity, Pen-profiles, Health, School

Mobile health apps to facilitate self-care: a qualitative study of user experiences

Objective: Consumers are living longer, creating more pressure on the health system and increasing their requirement for self-care of chronic conditions. Despite rapidly-increasing numbers of mobile health applications (‘apps’) for consumers’ self-care, there is a paucity of research into consumer engagement with electronic self-monitoring. This paper presents a qualitative exploration of how health consumers use apps for health monitoring, their perceived benefits from use of health apps, and suggestions for improvement of health apps. Materials and Methods: ‘Health app’ was defined as any commercially-available health or fitness app with capacity for self-monitoring. English-speaking consumers aged 18 years and older using any health app for self-monitoring were recruited for interview from the metropolitan area of Perth, Australia. The semi-structured interview guide comprised questions based on the Technology Acceptance Model, Health Information Technology Acceptance Model, and the Mobile Application Rating Scale, and is the only study to do so. These models also facilitated deductive thematic analysis of interview transcripts. Implicit and explicit responses not aligned to these models were analyzed inductively.Results: Twenty-two consumers (15 female, seven male) participated, 13 of whom were aged 26–35 years. Eighteen participants reported on apps used on iPhones. Apps were used to monitor diabetes, asthma, depression, celiac disease, blood pressure, chronic migraine, pain management, menstrual cycle irregularity, and fitness. Most were used approximately weekly for several minutes per session, and prior to meeting initial milestones, with significantly decreased usage thereafter. Deductive and inductive thematic analysis reduced the data to four dominant themes: engagement in use of the app; technical functionality of the app; ease of use and design features; and management of consumers’ data. Conclusions: The semi-structured interviews provided insight into usage, benefits and challenges of health monitoring using apps. Understanding the range of consumer experiences and expectations can inform design of health apps to encourage persistence in self-monitoring