Hypoxaemia and cardiocirculatory abnormalities may impair muscle oxygen (O
) delivery relative to O
requirements thereby increasing the rate of O
extraction during incremental exercise in fibrotic ...interstitial lung disease (f-ILD). Using changes in deoxyhaemoglobin concentration (HHb) by near-infrared spectroscopy (NIRS) as a proxy of O
extraction, we investigated whether a simplified (double-linear) approach, previously tested in heart failure, would provide useful estimates of muscle deoxygenation in f-ILD.
A total of 25 patients (23 men, 72 ± 8 years; 20 with idiopathic pulmonary fibrosis, lung diffusing capacity for carbon monoxide = 44 ± 11% predicted) and 12 age- and sex-matched healthy controls performed incremental cycling to symptom limitation. Changes in vastus lateralis HHb assessed by NIRS were analysed in relation to work rate (WR) and O
uptake throughout the exercise.
Patients showed lower exercise capacity than controls (e.g., peak WR = 67 ± 18% vs. 105 ± 20% predicted, respectively; p < 0.001). The HHb response profile was typically S-shaped, presenting three distinct phases. Exacerbated muscle deoxygenation in patients versus controls was evidenced by: (i) a steeper mid-exercise HHb-WR slope (0.30 ± 0.22 vs. 0.11 ± 0.08 μmol/W; p = 0.008) (Phase 2), and (ii) a larger late-exercise increase in HHb (p = 0.002) (Phase 3). Steeper HHb-WR slope was associated with lower peak WR (r = -0.70) and greater leg discomfort (r = 0.77; p < 0.001) in f-ILD.
This practical approach to interpreting HHb during incremental exercise might prove useful to determine the severity of muscle deoxygenation and the potential effects of interventions thereof in hypoxemic patients with f-ILD.
The present study aims to assess the clinical and hemodynamic impact of percutaneous edge-to-edge mitral valve repair with MitraClip in patients with atrial functional mitral regurgitation (A-FMR) ...compared with ventricular functional mitral regurgitation (V-FMR). Mitral regurgitation (MR) grade, functional status (New York Heart Association class), and major adverse cardiac events (MACE; all-cause mortality or hospitalization for heart failure) were evaluated in 52 patients with A-FMR and in 307 patients with V-FMR. In 56 patients, hemodynamic assessment during exercise echocardiography was performed before and 6 months after intervention. MR reduction after MitraClip implantation was noninferior in A-FMR compared with V-FMR (MR grade ≤2 at 6 months in 94% vs 82%, respectively, p <0.001 for noninferiority) and was associated with improvement of functional status (New York Heart Association class ≤2 at 6 months in 90% vs 80%, respectively, p = 0.2). Hemodynamic assessment revealed that cardiac output at 6 months was higher in A-FMR at rest (5.1 ± 1.5 L/min vs 3.8 ± 1.5 L/min, p = 0.002) and during peak exercise (7.9 ± 2.4 L/min vs 6.1 ± 2.1 L/min, p = 0.02). In addition, the reduction in systolic pulmonary artery pressure at rest was more pronounced in A-FMR: Δ SPAP −13.1 ± 15.1 mm Hg versus −2.2 ± 13.3 mm Hg (p = 0.03). MACE rate at follow-up was significantly lower in A-FMR versus V-FMR, with an adjusted odds ratio of 0.46 (95% confidence interval 0.24 to 0.88), which was caused by a reduction in hospitalization for heart failure. In conclusion, percutaneous edge-to-edge mitral valve repair with MitraClip is at least as effective in A-FMR as in V-FMR in reducing MR. However, the hemodynamic improvement and reduction of MACE were significantly better in A-FMR.
This article presents the modeling of multivariate extreme values using copulas. Our approach allows us to model the dependence structure independently of the marginal distributions, which is not ...possible with standard classical methods. The methodology has been applied on two different problems in hydrology. The first application is concerned with the combined risk in the framework of frequency analysis. Four copulas have been tested on peak flows from the watershed of Peribonka in Québec, Canada. The second application relates to the joint modeling of peak flows and volumes. Three copulas have been applied to the watershed of the Rimouski River in Québec, Canada. This approach using copulas is promising since it allows us to take into account a wide range of correlation which can happen in hydrology.
Exercise training as part of pulmonary rehabilitation is arguably the most effective intervention to improve tolerance to physical exertion in patients with chronic obstructive pulmonary disease ...(COPD). Owing to the fact that exercise training has modest effects on exertional ventilation, operating lung volumes and respiratory muscle performance, improving locomotor muscle structure and function are key targets for pulmonary rehabilitation in COPD. In the current concise review, we initially discuss whether patients' muscles are exposed to deleterious factors. After presenting corroboratory evidence on this regard (e.g., oxidative stress, inflammation, hypoxemia, inactivity, and medications), we outline their effects on muscle macro- and micro-structure and related functional properties. We then finalize by addressing the potential beneficial consequences of different training strategies on these muscle-centered outcomes. This review provides, therefore, an up-to-date outline of the rationale for rehabilitative exercise training approaches focusing on the locomotor muscles in this patient population.
Belgian primary schools very rarely adopt an outdoor learning approach. Yet most geography and science teacher trainers involved in pre-service teacher training see the environment around schools as ...a resource on which to develop learning in all disciplines, and a place to develop environmental and eco-citizenship education. Training teachers to follow this vision is hard, especially now with a generation of students who have a self-confined lifestyle, lack interest in walking and have almost no connection with nature. In the Haute École Libre mosane (Liège, Belgium), an alternative strategy based on a service-learning approach was tested for two years during a whole term: volunteer students followed an eco-traineeship in a non-formal organization, for which they had to design and complete an environmental education project. The main results of this action research are presented here.
Massively obese subjects frequently undergo pulmonary function tests nowadays. Obesity-associated decreases in key operating lung volumes (reduced inspiratory capacity and reduced vital capacity) are ...particularly concerning because they may shorten the "room" for tidal volume expansion with negative physiologic and sensory consequences.
Is massive obesity associated with reduced operating lung volumes? If so, is this effect more pronounced in men than women?
We performed an observational, retrospective study in a tertiary, hospital-based laboratory. Pulmonary function test results from 248 super-obese (SO; BMI, 50 to 59.9 kg/m
) and 83 super-super obese (SSO; BMI, ≥60 kg/m
) men and women were analyzed. Electronic medical records were screened to ensure that subjects were free of any disease that potentially could interfere with lung volumes.
The prevalence of a low total lung capacity (restriction) was 26.9%, which increased to 38.6% in SSO. Despite the absence of between-sex differences in BMI and spirometric variables derived from the forced maneuver in both SO and SSO, men presented with higher prevalence of restriction (46.7%) than women (19.4%) (P < .05). Between-sex differences in residual volume differed according to the BMI group; SO men presented with higher values than SO women; the opposite was found in the SSO group. The prevalence of restriction with low operating lung volumes was approximately twice (SSO) and approximately thrice (SSO) as high in men compared with women (P < .01). Linear prediction equations as a function of sex, demographic, and anthropometric attributes markedly reduced the prevalence of these abnormalities across the population.
Obesity-related restriction leading to low operating lung volumes is highly prevalent in the massively obese subject, particularly in men. These alterations that are associated with massive obesity should be taken into consideration for an accurate interpretation of pulmonary function tests in this growing population.
"Exercise starts and ends in the brain": this was the title of a review article authored by Dr. Bengt Kayser back in 2003. In this piece of work, the author highlights that pioneer studies have ...primarily focused on the cardiorespiratory-muscle axis to set the human limits to whole-body exercise tolerance. In some circumstances, however, exercise cessation may not be solely attributable to these players: the central nervous system is thought to hold a relevant role as the ultimate site of exercise termination. In fact, there has been a growing interest relative to the "brain" response to exercise in chronic cardiorespiratory diseases, and its potential implication in limiting the tolerance to physical exertion in patients. To reach these overarching goals, non-invasive techniques, such as near-infrared spectroscopy and transcranial magnetic stimulation, have been successfully applied to get insights into the underlying mechanisms of exercise limitation in clinical populations. This review provides an up-to-date outline of the rationale for the "brain" as the organ limiting the tolerance to physical exertion in patients with cardiorespiratory diseases. We first outline some key methodological aspects of neuromuscular function and cerebral hemodynamics assessment in response to different exercise paradigms. We then review the most prominent studies, which explored the influence of major cardiorespiratory diseases on these outcomes. After a balanced summary of existing evidence, we finalize by detailing the rationale for investigating the "brain" contribution to exercise limitation in hitherto unexplored cardiorespiratory diseases, an endeavor that might lead to innovative lines of applied physiological research.
Purpose
To identify which physical properties of nanoparticles are correlated with the survival fraction of cells exposed in vitro to low‐energy protons in combination with nanoparticles.
Methods
The ...Geant4 simulation toolkit (version 10.3) was used to model nanoparticles of different sizes (5–50 nm) and materials (Ti, Zr, Hf, Ta, Au, Pt), with or without an organic capping ensuring biocompatibility and to irradiate them with 1.3 or 4 MeV protons and 5.3 MeV alpha particles. The spectra of secondary electrons inside and at the nanoparticle surface were computed, as well as electron yields, Auger and organic capping contribution, trapping in metal bulk and linear energy transfer profiles as a function of distance from the nanoparticle center. In a next step, an in silico cell model was designed and loaded with gold nanoparticles, according to experimental uptake values. Dose to the cell was evaluated macroscopically and microscopically in 100 × 100 × 100 nm³ voxels for different radiation qualities.
Results
The cell geometry showed that radiation enhancement is negligible for the gold concentration used and for any radiation quality. However, when the single nanoparticle geometry is considered, we observed a local LET in its vicinity considerably higher than for the water equivalent case (up to 5 keV/μm at the titanium nanoparticle surface compared to 2.5 keV/μm in the water case). The yield of secondary electrons per primary interaction with 1.3 MeV protons was found to be most favorable for titanium (1.54), platinum (1.44), and gold (1.32), although results for higher Z metals are probably underestimated due to the incomplete simulation of de‐excitation cascade in outer shells. It was also found that the organic capping contributed mostly to the production of low‐energy electrons, adding a spike of dose near the nanoparticle surface. Indeed, the yield for the coated gold nanoparticle increased to 1.53 when exposed to 1.3 MeV protons. Although most electrons are retained inside larger nanoparticles (50 nm), it was shown that their yield is comparable to smaller sizes and that the linear energy transfer profile is better. From a combination of ballistic and nanoparticle size factors, it was concluded that 10‐nm gold nanoparticles were better inducers of additional cell killing than 5‐nm gold nanoparticles, matching our previous in vitro study.
Conclusions
Although effects from a physical standpoint are limited, the high linear energy transfer profile at the nanoparticle surface generates detrimental events in the cell, in particular ROS‐induced damage and local heating.
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