Understanding Exercise Capacity: From Elite Athlete to HFpEF.

Exercise capacity is a spectrum that reflects an individual's functional capacity and the dynamic nature of cardiac remodelling along with respiratory and skeletal muscle systems. The relationship of increasing physical activity, increased cardiac mass and volumes, and improved cardiorespiratory fitness (CRF) is well established in the endurance athlete. However, less emphasis has been placed on the other end of the spectrum, which includes individuals with a more sedentary lifestyle and small hearts who are at increased risk of functional disability and poor clinical outcomes. Reduced CRF is an independent predictor of all-cause mortality and cardiovascular events determined by multiple inter-related exogenous and endogenous factors. In this review, we explore the relationship of physical activity, cardiac remodelling, and CRF across the exercise spectrum, emphasising the critical role of cardiac size in determining exercise capacity. In contrast to the large compliant left ventricle of the endurance athlete, an individual with a lifetime of physical inactivity is likely to have a small, stiff heart with reduced cardiac reserve. We propose that this might contribute to the development of heart failure with preserved ejection fraction in certain individuals, and is key to understanding the link between low CRF and increased risk of heart failure.

Novel Epicardial Access Technique Facilitated by Carbon Dioxide Insufflation of the Pericardium for Ablation of Ventricular Arrhythmias: Lessons From the Early Experience From a Single Centre in Australia.

INTRODUCTION: Epicardial access for mapping and ablation of the epicardial substrate may be required in catheter ablation of ventricular tachycardias (VT). However, high complication rates are associated with the standard epicardial access approach. Recently, a novel method of intentional coronary vein (CV) exit with pericardial CO2 insufflation to facilitate epicardial access has been described. This study describes our initial experience with this technique. METHODS: Patients undergoing epicardial VT ablation between 1 February 2021 to 31 May 2022 at the Royal Prince Alfred Hospital, Sydney, NSW, were included in this study. Via femoral venous access, a branch of the coronary sinus was sub-selected and intentional CV exit was performed with a high tip load coronary angioplasty wire. A microcatheter was then advanced over the wire into the pericardial space, followed by pericardial CO2 insufflation, facilitating subxiphoid pericardial puncture. RESULTS: Five (5) patients underwent epicardial access for VT mapping and ablation. All patients had successful intentional CV exit and CO2 facilitated epicardial access. The mean time to successful epicardial access was 37.2±17.5 minutes. With increasing operator experience, there was improvement in epicardial access times, with the fifth case requiring only 13 minutes. There was one case of inadvertent right ventricular puncture (without haemodynamic or ventilatory compromise) due to inappropriate CO2 insufflation into the right ventricle. Epicardial access was successful on the second attempt. CONCLUSION: This is the first case series of epicardial access facilitated by CO2 insufflation in Australia. This technique enabled successful epicardial access in all patients in our early experience, with no adverse outcomes from epicardial access. With increasing operator experience, this technique may allow for more widespread adoption of up-front epicardial access for the treatment of VT.

Body Composition in Young Adults Living With a Fontan Circulation: The Myopenic Profile.

Background We sought to characterize body composition abnormalities in young patients living with a Fontan circulation and explore potential pathophysiologic associations. Methods and Results Twenty-eight patients with a Fontan circulation were prospectively recruited in this cross-sectional study. Participants underwent cardiopulmonary exercise testing, dual-energy X-ray absorptiometry, echocardiography, and biochemical assessment. Mean age was 26±7 years. Skeletal muscle mass, estimated by appendicular lean mass index Z score, was reduced compared with reference data (-1.49±1.10, P<0.001). Percentage body fat Z score overall was within normal range (0.23±1.26, P=0.35), although 46% had elevated adiposity. Those with reduced skeletal muscle mass (appendicular lean mass index Z score of -1 or lower) had lower percent predicted oxygen pulse (55±15 versus 76±16%, P=0.002). Overall agreement between body mass index and dual-energy X-ray absorptiometry to assess adiposity was fair only (weighted [linear] κ coefficient: 0.53; 95% CI, 0.34-0.73) and slight in the setting of muscle mass deficiency (weighted κ coefficient: 0.32; 95% CI, 0.13-0.50). Appendicular lean mass was independently associated with absolute peak VO2 (ß=70.6 mL/min, P=0.001). Appendicular lean mass index Z score was inversely associated with hemoglobin (r=-0.4, P=0.04), and the degree of muscle deficit was associated with ventricular systolic impairment. Conclusions Young patients with a Fontan circulation have a body composition characterized by reduced skeletal muscle mass, which is associated with peak exercise capacity. Increased adiposity is common despite a normal body mass index. Low skeletal muscle mass is associated with systolic dysfunction and compensatory erythrocytosis.

Prevalence and risk factors for low bone density in adults with a Fontan circulation.

OBJECTIVE AND PATIENTS: This study aimed to characterize bone mineral density abnormalities and pathophysiological associations in young adults living with a Fontan circulation. DESIGN: Participants underwent bone mineral density measurement using dual-energy X-ray absorptiometry and serum biochemical analysis, cardiopulmonary exercise and strength testing and transthoracic echocardiography. RESULTS: In our cohort (n = 28), 29% had osteopenic-range bone mineral density and one patient was osteoporotic (average hip t score: -0.6 ± 1.1; spine t score: -0.6 ± 0.9). Four patients (14%) had z scores < -2.0. Parathyroid hormone levels were increased compared with laboratory median (6.1 ± 3.5 vs 4 pmol/L, P = .01) and 27% had 25-hydroxy-vitamin D < 50 nmol/L. 25-hydroxy-vitamin D negatively correlated with parathyroid hormone (ρ = -0.53, P = .01) suggesting secondary hyperparathyroidism. Atrioventricular valve systolic to diastolic duration ratio, an echocardiographic measure of diastolic dysfunction, inversely correlated with hip t and z scores (P < .01). Hip t scores were positively associated with oxygen saturations (ρ = 0.45, P = .05) and tended to be inversely associated with parathyroid hormone levels (ρ = -0.44, P = .07) and N-Terminal pro b-type natriuretic peptide (ρ = -0.42, P = .08). CONCLUSIONS: Many young adults with a Fontan circulation have abnormal bone mineral density. The underlying pathophysiology is likely multifactorial. Possible contributors include secondary hyperparathyroidism, hypoxemia, diastolic cardiac dysfunction and neurohormonal activation. As low bone mineral density is clinically relevant and potentially treatable, assessment of bone mineral density should be part of routine care in this cohort.

The concreteness of abstract language: an ancient issue and a new perspective.

This paper addresses the debated issue of abstract language in the framework of embodiment. First, we discuss the notion of abstractness in the light of the Western philosophical thought, with a focus on the English empiricist tradition. Second, we review the most relevant psychological models and neuroscientific empirical findings on abstract language. It turns out that abstract words are not such, because their meaning is "far from experience", but, because of the high complexity of the attached experiential clusters. Finally, we spell out the consequences of this understanding of abstractness in relation to the neural mechanisms subserving abstract language processing. If abstract words, as compared to concrete ones, imply an increasing complexity of the associated experiential clusters, then the processing of abstract language relies on the recruitment of several neural substrates coding for those experiences. We forward that, at the neural level, this complexity is coded by means of three main mechanisms: (1) the recruitment of the motor representations of different biological effectors (abstract meaning as effector-unspecific); (2) the recruitment of different systems, including sensory, motor, and emotional ones (abstract meaning as multi-systemic); (3) the recruitment of neural substrates coding for social contexts and levels of self-relatedness (abstract meaning as dynamic). As compared to the current approaches in the literature on abstract language that combine embodiment with some a-modal aspects, our proposal is fully embodied and rules out additional aspects. Our proposal may spur future empirical research on abstract language in the embodied approach.

Transcriptomic Analysis of Planarians under Simulated Microgravity or 8 g Demonstrates That Alteration of Gravity Induces Genomic and Cellular Alterations That Could Facilitate Tumoral Transformation.

The possibility of humans to live outside of Earth on another planet has attracted the attention of numerous scientists around the world. One of the greatest difficulties is that humans cannot live in an extra-Earth environment without proper equipment. In addition, the consequences of chronic gravity alterations in human body are not known. Here, we used planarians as a model system to test how gravity fluctuations could affect complex organisms. Planarians are an ideal system, since they can regenerate any missing part and they are continuously renewing their tissues. We performed a transcriptomic analysis of animals submitted to simulated microgravity (Random Positioning Machine, RPM) (s-µg) and hypergravity (8 g), and we observed that the transcriptional levels of several genes are affected. Surprisingly, we found the major differences in the s-µg group. The results obtained in the transcriptomic analysis were validated, demonstrating that our transcriptomic data is reliable. We also found that, in a sensitive environment, as under Hippo signaling silencing, gravity fluctuations potentiate the increase in cell proliferation. Our data revealed that changes in gravity severely affect genetic transcription and that these alterations potentiate molecular disorders that could promote the development of multiple diseases such as cancer.

Conservation of Mediterranean seascapes: analyses of existing protection schemes.

Marine protected areas (MPAs) are aimed at managing and protecting marine environments. Their design, however, often disregards both a thorough knowledge of the distribution of habitats and assemblages and the use of proper experimental evaluations of the efficacy of MPAs by comparing protected vs. unprotected zones. About 200 MPAs have been recently instituted in the Mediterranean area, but the evidence of their efficacy is scant. The MPA of Torre Guaceto (Southern Adriatic Sea, Italy) is one of the rare cases of effective protection enforcement. The reserve was instituted more than 10 years ago, a period currently considered as sufficient to show responses by organisms to protection. The MPA is divided into a C zone, the general reserve, where many activities are permitted, a B zone, the partial reserve where restrictions increase and two A zones, the integral reserve where access is prohibited. The goals of the paper were to map the distribution of benthic assemblages to assess if they were properly represented in the differently protected zones, and to test the efficacy of protection by quantifying possible differences between the assemblages in two control areas and in the two A zones, where human impact is completely excluded. The analysis of habitat and assemblage distribution within the MPA showed that the zones with total protection do not include most valuable environmental types. Most of the considered variables (i.e. cover of substratum, number of taxa, and average abundance of the most common taxa) were not significantly different in and out of the A zones, at each time of sampling. Results, however, suggested a possible effect of protection in modifying patterns of abundance of sponges under Cystoseira canopy (more abundant in the fully protected zone). In the subtidal habitat, differences were found in the structure of the whole assemblage and in the abundance of encrusting coralline red algae (more abundant outside the fully protected area). Notwithstanding the correct general methodology employed in the study, a lack of statistical power could have a role in preventing the detection of ecologically relevant effects of protection. In some instances, data pooling allowed a discrimination between cases where there was clearly no effect of protection and cases where there might be. On this basis, the optimization of this experimental design should be considered in further studies. In any case, if the goals of MPAs have not been clearly stated, efficacy of protection might prove very difficult to test even with the use of sound experimental designs.