[Effects of gender on pulmonary rehabilitation outcomes in patients with COPD]. / Impact du genre sur les effets de la réadaptation respiratoire chez les patients atteints de BPCO.

INTRODUCTION: COPD has become more prevalent among women, revealing a specific feminine phenotype. Women experience greater dyspnea and a more impaired quality of life. The main objective of this study was to assess the effect of gender on dyspnea during a pulmonary rehabilitation program (PRP). METHODS: Retrospective study including COPD patients having participated in PRPs. The following data were analyzed according to gender before and after a PRP: dyspnea, quality of life, anxiety and depression, exercise capacity, muscle function (quadriceps and inspiratory muscles). RESULTS: More than 500 patients (252 men and 252 women) were included. We did not find a significant effect of gender on the evolution of dyspnea, anxiety or depressive disorders, exercise capacity, inspiratory muscle strength, or overall quality of life score. That said, we found a possible effect on the sub-scores of the quality of life questionnaire, and regarding quadriceps strength. All criteria improved during the program in both groups. CONCLUSIONS: During a PRP, gender does not impact the evolution of dyspnea. While women may nonetheless benefit to a greater extent in terms of quality of life sub-scores (impact, activities, symptoms) and quadriceps strength, these results still require confirmation.

Coprophagia in early life tunes expression of immune genes after weaning in rabbit ileum.

Coprophagia by suckling rabbits, i.e. ingestion of feces from their mother, reduces mortality after weaning. We hypothesized that this beneficial effect of coprophagia is immune-mediated at the intestinal level. Therefore, this study investigated immune development after weaning by analyzing the ileal transcriptome at day 35 and 49 in rabbits with differential access to coprophagia in early life. Rabbit pups had access between day 1 and 15 to (i) no feces (NF) or (ii) feces from unrelated does (Foreign Feces, FF) or (iii) feces from unrelated does treated with antibiotics (FFab). 350 genes were differentially expressed between day 35 and day 49 in suckling rabbits with access to coprophagia. These genes coded for antimicrobial peptides, a mucin, cytokines and chemokines, pattern recognition receptors, proteins involved in immunoglobulin A secretion and in interferon signaling pathway. Strikingly, prevention of coprophagia or access to feces from antibiotic-treated does in early life blunted immune development between day 35 et 49 in the ileum of rabbits. Thus, coprophagia might be crucial for the maturation of intestinal immunity in rabbits and could explain why this behavior improves survival.

Evaluation of utero-placental vascularization using contrast-enhanced ultrasound: Early first trimester maternal perfusion of the intervillous space is confirmed.

INTRODUCTION: The objective was to confirm and semiquantify the maternal perfusion of the intervillous space between 8 and 13 + 6 gestational weeks (GW). METHODS: We conducted a prospective, multicenter, and nonrandomized open study. Women undergoing voluntary termination of pregnancy at three different gestational ages (Group 8 GW: 8 to 8 + 6 GW, Group 11GW: 11 to 11 + 6 GW and Group 13GW: 13 to 13 + 6 GW) were included, with 14 subjects per group. Women presenting with a personal risk of preeclampsia and/or intrauterine growth restriction were excluded. Contrast-enhanced ultrasound (CEUS) was performed with an intravenous bolus administration of 2.4 mL of microbubbles. The region of interest (ROI) was the entire placenta. The perfusion curves and kinetic parameters, including wash-in perfusion index, peak enhancement and mean transit time, were calculated. RESULTS: Of the 42 women initially included, interpretable perfusion curves could be obtained for 33. Regardless of the gestational age, contrast was observed in the entire placenta. No significant difference in perfusion parameters was observed between groups. There was an association between signal intensity and both maternal heart frequency and placental location. Signal intensity was decreased when the heart frequency increased (p < 0.05) and when the placenta was in a nonanterior position (p > 0.005). DISCUSSION: We confirmed the presence of maternal perfusion of the intervillous space as early as 8 GW. No significant increase in perfusion parameters was observed between 8 and 13 + 6 GW. Our observations, in accordance with the previous experiment published by Roberts et al.1, strongly challenge the classic trophoblastic plug theory.

[The role of the physiotherapist in the assessment and management of dyspnea]. / Le rôle du kinésithérapeute dans l'évaluation et la gestion de la dyspnée.

The role of the physiotherapist in the assessment and management of dyspnea. Dyspnea is the most common symptom in cardio-respiratory diseases. Recently improved comprehension of dyspnea mechanisms have underlined the need for three-faceted assessment. The three key aspects correspond to the "breathing, thinking, functioning" clinical model, which proposes a multidimensional - respiratory, emotional and functional - approach. Before initiating treatment, it is essential for several reasons to assess each specific case, determining the type of dyspnea affecting the patient, appraising the impact of shortness of breath, and estimating the effectiveness of the treatment applied. The physiotherapist has a major role to assume in the care of dyspneic patients, not only in assessment followed by treatment but also as a major collaborator in a multidisciplinary team, especially with regard to pulmonary rehabilitation. The aim of this review is to inventory the existing assessment tools and the possible physiotherapies for dyspnea, using a holistic approach designed to facilitate the choice of techniques and to improve quality of care by fully addressing the patient's needs.

Assessment of placental perfusion using contrast-enhanced ultrasound: A longitudinal study in pregnant rabbit.

OBJECTIVES: The main aim of the study was to quantitatively characterize placental perfusion using contrast-enhanced ultrasound in a longitudinal study performed in pregnant rabbits. As a secondary objective, we qualitatively assessed the placental perfusion. METHODS: Three pregnant rabbits were used. Contrast-enhanced ultrasound was performed twice for each dam, either on embryo development (ED) day 14, 21 or 28 of pregnancy, under general anesthesia. Both qualitative and quantitative analyses were performed based on ultrasound assessment. RESULTS: Altogether, data from 29 fetuses were analyzed: 10 at ED-14; 12 at ED-21, and 7 at ED-28. Placental vascularization was mainly peripheral at the earliest gestational age and became gradually homogeneous within the whole placenta as pregnancy progressed. Intensity parameters and relative blood flows significantly increased with gestational age. The wash-in and wash-out rates were correlated and a significant increase in wash-in compared to in wash-out rates was observed with increased gestational age. CONCLUSION: Contrast-enhanced ultrasound is feasible in animal models and allows qualitative and quantitative analysis of placental vascularization during pregnancy.

New insights into human functional ultrasound imaging.

Ultrasound imaging is a vital tool for exploring in vivo the placental function which is essential to understand pathological phenomena such as preeclampsia or intrauterine growth restriction. As technology advances including ready availability of three-dimensional (3D) probes and novel software, new markers of placental function become possible. The objective of this review was to provide an overview of the new ultrasound markers of placental function with a focus on the potential clinical application of three-dimensional power Doppler (3DPD). A broad-free text literature search was undertaken based on human placental studies and sixty full-text studies were included in this review. Three-dimensional power Doppler is a promising technique to predict preeclampsia in the first trimester. However, the influence of external factors such as body mass index, parameter standardisation and machine settings still need to be addressed. Contrast-enhanced ultrasound is currently reserved for research, because the required injected contrast mediums are not currently approved for use in pregnancy, although the safety data is reassuring.

Comparison of the cardio-respiratory response of a training session on cycloergometer or treadmill versus an Adapted Physical Activity session on Nintendo Wii, in patients with chronic respiratory disease.

OBJECTIVES: During a pulmonary rehabilitation program (PRP), patients frequently report that the classically proposed activities (as cycloergometer or treadmill) are not playful. The goal of adapted physical activities is to maintain physical activity that is more playful for patients. The Nintendo Wii Gaming Console allows a playful physical activity. However, it seems important to know if this tool allows physical activity with an effective cardiorespiratory effect. The objective was to compare the cardiorespiratory response of a 30-minute training session on cycloergometer (C) and treadmill (T) versus a 30-minute training session with Wii. METHODS: Patients admitted to the PR unit of Brest University Hospital (France) were eligible for this randomized study if they had a chronic pulmonary disease. The endpoints were heart rate (HR), pulse oxymetry, dyspnea, lower limb penibility and pleasure felt. RESULTS: Twenty patients were prospectively included. HR was significantly higher at the end of the Wii session in comparison with C session (P=0.001); there was no significant difference in HR between Wii and T. We found no significant difference for dyspnea and lower limb penibility between Wii and C (respectively P=0.8 and P=0.7) and between Wii and T (respectively P=0.96 and P=0.5). The pleasure felt was significantly greater during Wii compared to C and T (respectively P=0.001 and P=0.001). CONCLUSIONS: Exercise training using Wii with identifiable games require higher HR at the end of the session compared to C and a similar cardiorespiratory response compared to T with the same dyspnea and lower limb exertion and with a pleasure felt significantly higher. Wii can be used for exercise training during PRP.

[Inspiratory muscle training during pulmonary rehabilitation]. / L'entraînement des muscles inspiratoires en réhabilitation respiratoire.

INTRODUCTION: Inspiratory muscle training (IMT) is part of the management of patients with pulmonary diseases during rehabilitation. Since the last recommendations of the Société de pneumologie de langue française, several studies have focused on the role of inspiratory muscle training during pulmonary rehabilitation. BACKGROUND: IMT, in comparison to standard care or sham-IMT, improves the strength and endurance of the inspiratory muscles, decreases dyspnoea during the activities of daily living, improves walking distance and quality of life. However, the different studies did not show an additional effect of IMT during a pulmonary rehabilitation program compared to a rehabilitation program without IMT, with regard to improvement of exercise capacity and quality of life. OUTLOOK: One study showed an improvement in dyspnoea of effort, but these results are yet to be confirmed. Finally, it seems appropriate to associate IMT with an exercise-training program before chest or abdominal surgery, even if further studies are necessary. CONCLUSION: During a pulmonary rehabilitation program, IMT does not provide additional benefits. However, when patients cannot perform a global exercise training, IMT has shown benefit. IMT provides additional benefits in pre-operative programs.

Possible observation of the signature of the bad metal phase and its crossover to a Fermi liquid in κ-(BEDT-TTF)2Cu(NCS)2 bulk and nanoparticles by Raman scattering.

κ-(BEDT-TTF)2Cu(NCS)2 has been investigated by Raman scattering in both bulk and nanoparticle compounds. Phonon modes from 20 to 1600 cm-1 have been assigned. Focusing on the unexplored low frequency phonons, a plateau in frequencies is observed in the bulk phonons between 50 and 100 K and assigned to the signature of the bad metal phase. Nanoparticles of κ-(BEDT-TTF)2Cu(NCS)2 exhibit anomalies at 50 K associated to the crossover from a bad metal to a Fermi liquid whose origins are discussed.

Design and evaluation of an abbreviated pixelwise dynamic contrast enhancement analysis protocol for early extracellular volume fraction estimation.

INTRODUCTION: T1-based method is considered as the gold standard for extracellular volume fraction (ECV) mapping. This technique requires at least a 10 min delay after injection to acquire the post injection T1 map. Quantitative analysis of Dynamic Contrast Enhancement (DCE) images could lead to an earlier estimation of an ECV like parameter (2 min). The purpose of this study was to design a quantitative pixel-wise DCE analysis workflow to assess the feasibility of an early estimation of ECV. METHODS: Fourteen patients with mitral valve prolapse were included in this study. The MR protocol, performed on a 3 T MR scanner, included MOLLI sequences for T1 maps acquisition and a standard SR-turboFlash sequence for dynamic acquisition. DCE data were acquired for at least 120 s. We implemented a full DCE analysis pipeline with a pre-processing step using an innovative motion correction algorithm (RC-REG algorithm) and a post-processing step using the extended Tofts Model (ECVETM). Estimated ECVETM maps were compared to standard T1-based ECV maps (ECVT1) with both a Pearson correlation analysis and a group-wise analysis. RESULTS: Image and map quality assessment showed systematic improvements using the proposed workflow. Strong correlation was found between ECVETM, and ECVT1 values (r-square = 0.87). CONCLUSION: A DCE analysis workflow based on RC-REG algorithm and ETM analysis can provide good quality parametric maps. Therefore, it is possible to extract ECV values from a 2 min-long DCE acquisition that are strongly correlated with ECV values from the T1 based method.

Contribution of the gut microbiota to the regulation of host metabolism and energy balance: a focus on the gut-liver axis.

This review presents mechanistic studies performed in vitro and in animal models, as well as data obtained in patients that contribute to a better understanding of the impact of nutrients interacting with the gut microbiota on metabolic and behavioural alterations linked to obesity. The gut microbiota composition and function are altered in several pathological conditions including obesity and related diseases i.e. non-alcoholic fatty liver diseases (NAFLD). The gut-liver axis is clearly influenced by alterations of the gut barrier that drives inflammation. In addition, recent papers propose that specific metabolites issued from the metabolic cooperation between the gut microbes and host enzymes, modulate inflammation and gene expression in the liver. This review illustrates how dietary intervention with prebiotics or probiotics influences host energy metabolism and inflammation. Indeed, intervention studies are currently underway in obese and NAFLD patients to unravel the relevance of the changes in gut microbiota composition in the management of metabolic and behavioural disorders by nutrients interacting with the gut microbiota. In conclusion, diet is among the main triggers of NAFLD and the gut microbiota is modified accordingly, underlining the importance of the concomitant study of the nutrients and microbial impact on liver health and metabolism, in order to propose innovative, clinically relevant, therapeutic approaches.

[Follow-up and evaluation of plans developed during pulmonary rehabilitation]. / Suivi et évaluation sur une année de projets élaborés en réhabilitation respiratoire.

BACKGROUND: Pulmonary rehabilitation inevitably contains two essential components: therapeutic education and exercise training. The principal aim of this study was to evaluate the evolution over a year of the realization of plans determined during a pulmonary rehabilitation program (PRP). METHODS: At the end of a PRP the patient made plans in accordance with his health condition. A telephone enquiry was undertaken at 3, 7 and 12 months to evaluate the progress of the plans, the motivation to perform them, dyspnoea and quality of life. RESULTS: The data of 65 patients were analyzed (87 inclusions). Fifty-seven percent of the plans continued for one year. Walking had an adherence rating of 71%. Loss of motivation appeared to be the main cause for stopping (20%). Quality of life remained stable (p=0.39) and an increase in dyspnoea, though statistically significant (p<0.01), was of no clinical relevance. CONCLUSION: The majority of plans were maintained but without clinical effect on the quality of life or the level of dyspnoea. Decreased motivation was the major limitation to realization or continuation of the plans. New studies will have to be implemented to analyze the factors which lead to this decrease.

[Reproducibility of strength and endurance measurements of the quadriceps in patients with COPD]. / Reproductibilité de la mesure de la force et de l'endurance du quadriceps dans la BPCO.

INTRODUCTION: Patients with COPD frequently have lower strength and endurance in their lower limbs compared to healthy subjects and evaluation of their quadriceps strength is recommended in practice. The handheld dynamometer has been validated and is easy to use for this measurement but its reproducibility has never been studied for endurance evaluation and only poorly for strength. The objective of this study was to estimate the inter and intra-operator reproducibility of maximal voluntary strength and endurance measurements of the quadriceps with a handheld dynamometer in patients with COPD. METHODS: The measurements of maximal voluntary strength and endurance were performed with a single handheld dynamometer using isometric contraction. Three measurement sessions were undertaken, separated by 24hours. The intra- and interoperator reproducibility were estimated by calculation of the intraclass correlation coefficient. RESULTS: Overall, 21 patients were included in the study. The intraclass correlation coefficient calculated for the maximal voluntary strength for intra and interoperator reliability ranged between 0.95 and 0.99. For endurance, the coefficient for intra-operator reliability was 0.81 and the two for interoperator reliability were 0.69 and 0.77. CONCLUSION: The handheld dynamometer allows an excellent inter and intra-operator reproducibility for the measurement of quadricipital maximal voluntary strength and a correct to excellent reproducibility for the measurement of quadricipital endurance. This tool may be used for the evaluation of quadriceps strength in clinical practice in COPD patients, particularly during rehabilitation.

Untangling the relationship between diet and visceral fat mass through blood metabolomics and gut microbiome profiling.

BACKGROUND/OBJECTIVES: Higher visceral fat mass (VFM) is associated with an increased risk for developing cardio-metabolic diseases. The mechanisms by which an unhealthy diet pattern may influence visceral fat (VF) development has yet to be examined through cutting-edge multi-omic methods. Therefore, our objective was to examine the dietary influences on VFM and identify gut microbiome and metabolite profiles that link food intakes to VFM. SUBJECTS/METHODS: In 2218 twins with VFM, food intake and metabolomics data available we identified food intakes most strongly associated with VFM in 50% of the sample, then constructed and tested the 'VFM diet score' in the remainder of the sample. Using linear regression (adjusted for covariates, including body mass index and total fat mass), we investigated associations between the VFM diet score, the blood metabolomics profile and the fecal microbiome (n=889), and confirmed these associations with VFM. We replicated top findings in monozygotic (MZ) twins discordant (⩾1 s.d. apart) for VFM, matched for age, sex and the baseline genetic sequence. RESULTS: Four metabolites were associated with the VFM diet score and VFM: hippurate, alpha-hydroxyisovalerate, bilirubin (Z,Z) and butyrylcarnitine. We replicated associations between VFM and the diet score (beta (s.e.): 0.281 (0.091); P=0.002), butyrylcarnitine (0.199 (0.087); P=0.023) and hippurate (-0.297 (0.095); P=0.002) in VFM-discordant MZ twins. We identified a single species, Eubacterium dolichum to be associated with the VFM diet score (0.042 (0.011), P=8.47 × 10-5), VFM (0.057 (0.019), P=2.73 × 10-3) and hippurate (-0.075 (0.032), P=0.021). Moreover, higher blood hippurate was associated with elevated adipose tissue expression neuroglobin, with roles in cellular oxygen homeostasis (0.016 (0.004), P=9.82x10-6). CONCLUSIONS: We linked a dietary VFM score and VFM to E. dolichum and four metabolites in the blood. In particular, the relationship between hippurate, a metabolite derived from microbial metabolism of dietary polyphenols, and reduced VFM, the microbiome and increased adipose tissue expression of neuroglobin provides potential mechanistic insight into the influence of diet on VFM.

Non-invasive evaluation of placental blood flow: lessons from animal models.

In human obstetrics, placental vascularisation impairment is frequent as well as linked to severe pathological events (preeclampsia and intrauterine growth restriction), and there is a need for reliable methods allowing non-invasive evaluation of placental blood flow. Uteroplacental vascularisation is complex, and animal models are essential for the technical development and safety assessment of these imaging tools for human clinical use; however, these techniques can also be applied in the veterinary context. This paper reviews how ultrasound-based imaging methods such as 2D and 3D Doppler can provide valuable insight for the exploration of placental blood flow both in humans and animals and how new approaches such as the use of ultrasound contrast agents or ultrafast Doppler may allow to discriminate between maternal (non-pulsatile) and foetal (pulsatile) blood flow in the placenta. Finally, functional magnetic resonance imaging could also be used to evaluate placental blood flow, as indicated by studies in animal models, but its safety in human pregnancy still requires to be confirmed.

Inspiratory muscle training during pulmonary rehabilitation in chronic obstructive pulmonary disease: A randomized trial.

Although recommended by international guidelines, the benefit of inspiratory muscle training (IMT) in addition to rehabilitation remains uncertain. The objective was to demonstrate the effectiveness of IMT on dyspnea using Borg scale and multidimensional dyspnea profile questionnaire at the end of a 6-minute walk test (6MWT) in patients with chronic obstructive pulmonary disease (COPD) with preserved average maximum inspiratory pressure (PImax) of 85 cm H2O (95% of predicted (pred.) value) and admitted for a rehabilitation program in a dedicated center. In a randomized trial, comparing IMT versus no IMT in 32 COPD patients without inspiratory muscle weakness (PImax >60 cm H2O) who were admitted for pulmonary rehabilitation (PR) for 3 weeks, we evaluated the effect of IMT on dyspnea, using both Borg scale and multidimensional dyspnea profile (MDP) at the end of the 6MWT, and on functional parameters included inspiratory muscle function (PImax) and 6MWT. All testings were performed at the start and the end of PR. In unadjusted analysis, IMT was not found to be associated with an improvement of either dyspnea or PImax. After adjustment on confounders (initial Borg score) and variables of interaction (forced expiratory volume in 1 second (FEV1)), we found a trend toward an improvement of "dyspnea sensory intensity", items from MDP and a significant improvement on the variation in the 2 items of MDP ("tight or constricted" and "breathing a lot"). In the subgroup of patients with FEV1 < 50% pred., 5 items of MDP were significantly improved, whereas no benefit was observed in patients with FEV1 > 50% pred. IMT did not significantly improve dyspnea or functional parameter in COPD patients with PImax > 60 cm H2O. However, in the subgroup of patients with FEV1 < 50% pred., MDP was significantly improved.

Complex trait architecture: the pleiotropic model revisited.

There is currently much debate about how much the genetic heritability of complex traits is due to very rare alleles. This issue is important because it determines sampling strategies for genetic association studies. Several recent theoretical papers based on a pleiotropic model for trait evolution suggest that it is possible that a large proportion of the genetic variance could be explained by rare alleles. This model assumes that mutations with a large effect on fitness also tend to have large positive or negative effects on phenotypic traits. We show that conclusions based on standard diffusion results are generally applicable to simulations of whole genomes with overlapping generations in a finite population, although the variance contribution of rare alleles is somewhat smaller than theoretical predictions. We show that under many scenarios the pleiotropic model predicts trait distributions that are unrealistically leptokurtic. We argue that this imposes a limit on the relationship between fitness and trait effects.