Rehabilitation of COPD patients: which training modality?

Non pharmacological therapy has been gaining more interest and has been evolving rapidly over the last decade as an essential part of therapy for COPD patients. Pulmonary Rehabilitation (PR), the most important non pharmacological treatment in patients with COPD, has a primary goal: to achieve the highest possible level of individual exercise tolerance, thus reducing the primary and/or secondary health care utilisation. The aim of the present review is to focus the role of exercise training in these patients as well as to address the question on which training methods are the most beneficial. We have therefore undertaken a MEDLINE-based search including the terms: pulmonary rehabilitation, exercise, lung disease/obstructive. Several strategies based on endurance or strength training are nowadays implemented during PR programmes in order to maximise the benefits for each patient. The impaired function of ambulation muscles causing breathlessness as one of the more frequent symptoms in many COPD, suggests that training the lower extremities is the most important goal to achieve during pulmonary rehabilitation of these patients. On the other hand, as muscle strength appears to be an independent contributor to survival and utilisation of health care resources, it seems largely justified also to include this further modality in the PR program of these patients. In conclusion, both modalities are effective and useful for COPD patients. However, whether resistance training should be administered to all COPD and which is the optimal length of strength training still needs to be elucidated

Length and clinical effectiveness of pulmonary rehabilitation in outpatients with chronic airway obstruction

Study objective: To assess the clinical effectiveness of pulmonary rehabilitation (PR) after 10 or 20 consecutive sessions in outpatients with chronic airway obstruction (CAO). Design: Observational prospective cohort trial. Setting: Outpatient clinic of a rehabilitation center. Patients and interventions: Twenty-five outpatients (mean age, 65 +/- 9 years [+/- SD]; FEV1, 64 +/- 12% predicted) admitted to a comprehensive PR program, including exercise training. Measurements and results: The load reached on a cycloergometer (maximal achieved load [W-max]), the maximal and isoload dyspnea and leg fatigue on a Borg scale, 6-min walk distance (6MWD), and the health-related quality of life as assessed using the St. George's Respiratory Questionnaire (SGRQ) [total and components score] have been recorded as outcome measures at baseline, after 10 sessions (T10), and after 20 sessions (T20). The predefined criteria of the clinically significant improvement were as follows: + 15% W-max, + 54 m at 6MWD, - 1 point at isoload dyspnea and leg fatigue, and - 4% at SGRQ scores. There was a mean significant difference between changes at T20 and T10 for 6MWD (- 42.96 m; 95% confidence interval [0], - 57.79 to - 28.12 m; p = 0.001), total SGRQ (4.80; 95% CI, 2.29 to 7.31; p = 0.001), activity SGRQ (3.60; 95% CI, 0.48 to 6.71; p = 0.025), and symptoms SGRQ (5.96; 95% CI, 2.72 to 9.2; p = 0.001). The percentage of patients who improved was different at T20 as compared with T 10 for W-max (68% and 48%, respectively; p = 0.025), 6MWD (76% and 20%, p = 0.001), and total SGRQ (64% and 36%, p = 0.008). Conclusions: A 10-session course of PR provides only limited clinically significant changes of outcome measures when compared with a 20-session course in outpatients with CAO of mild-to-moderate severity

Respiratory muscle training in patients recovering recent open cardio-thoracic surgery: a randomized-controlled trial.

Objectives- To evaluate the clinical efficacy and feasibility of an expiratory muscle training (EMT) device (Respilift™) applied to patients recovering from recent open cardio-thoracic surgery (CTS). Design- Prospective, double-blind, 14-day randomised-controlled trial. Participants and setting- 60 inpatients recovering from recent CTS and early admitted to a pulmonary rehabilitation program. Interventions- Chest physiotherapy plus EMT with a resistive load of 30 cm H2O for active group and chest physiotherapy plus EMT with a sham load for control group. Measures- Changes in maximal expiratory pressure (MEP) was considered as primary outcome, while maximal inspiratory pressures (MIP), dynamic and static lung volumes, oxygenation, perceived symptoms of dyspnoea, thoracic pain and well being (evaluated by visual analogic scale-VAS) and general health status were considered secondary outcomes. Results- All outcomes recorded showed significant improvements in both groups; however, the change of MEP (+34.2 mmHg, p<0.001 and +26.1%, p<0.001 for absolute and % of predicted, respectively) was significantly higher in Active group. Also VAS-dyspnoea improved faster and more significantly (p<0.05) at day 12 and 14 in Active group when compared with Control. The drop out rate was 6%, without differences between groups. Conclusions- In patients recovering from recent CTS specific EMT by Respilift™ is feasible and effective

Constitutive Expression of Insulin Receptor Substrate (IRS)-1 Inhibits Myogenic Differentiation through Nuclear Exclusion of Foxo1 in L6 Myoblasts

Insulin-like growth factors (IGFs) are well known to play essential roles in enhancement of myogenic differentiation. In this report we showed that initial IGF-I signal activation but long-term IGF-1 signal termination are required for myogenic differentiation. L6 myoblast stably transfected with myc-epitope tagged insulin receptor substrate-1, myc-IRS-1 (L6-mIRS1) was unable to differentiate into myotubes, indicating that IRS-1 constitutive expression inhibited myogenesis. To elucidate the molecular mechanisms underlying myogenic inhibition, IGF-I signaling was examined. IGF-I treatment of control L6 cells for 18 h resulted in a marked suppression of IGF-I stimulated IRS-1 association with the p85 PI 3-kinase and suppression of activation of Akt that correlated with a down regulation of IRS-1 protein. L6-mIRS1 cells, in contrast, had sustained high levels of IRS-1 protein following 18 h of IGF-I treatment with persistent p85 PI 3-kinase association with IRS-1, Akt phosphorylation and phosphorylation of the downstream Akt substrate, Foxo1. Consistent with Foxo1 phosphorylation, Foxo1 protein was excluded from the nuclei in L6-mIRS1 cells, whereas Foxo1 was localized in the nuclei in control L6 cells during induction of differentiation. In addition, L6 cells stably expressing a dominant-interfering form of Foxo1, Δ256Foxo1 (L6-Δ256Foxo1) were unable to differentiate into myotubes. Together, these data demonstrate that IGF-I regulation of Foxo1 nuclear localization is essential for the myogenic program in L6 cells but that persistent activation of IGF-1 signaling pathways results in a negative feedback to prevent myogenesis

Decarbonisation and its discontents: a critical energy justice perspective on four low-carbon transitions

Low carbon transitions are often assumed as normative goods, because they supposedly reduce carbon emissions, yet without vigilance there is evidence that they can in fact create new injustices and vulnerabilities, while also failing to address pre-existing structural drivers of injustice in energy markets and the wider socio-economy. With this in mind, we examine four European low-carbon transitions from an unusual normative perspective: that of energy justice. Because a multitude of studies looks at the co-benefits renewable energy, low-carbon mobility, or climate change mitigation, we instead ask in this paper: what are the types of injustices associated with low-carbon transitions? Relatedly, in what ways do low-carbon transitions worsen social risks or vulnerabilities? Lastly, what policies might be deployed to make these transitions more just? We answer these questions by first elaborating an “energy justice” framework consisting of four distinct dimensions—distributive justice (costs and benefits), procedural justice (due process), cosmopolitan justice (global externalities), and recognition justice (vulnerable groups). We then examine four European low-carbon transitions—nuclear power in France, smart meters in Great Britain, electric vehicles in Norway, and solar energy in Germany—through this critical justice lens. In doing so, we draw from original data collected from 64 semi-structured interviews with expert partisans as well as five public focus groups and the monitoring of twelve internet forums. We document 120 distinct energy injustices across these four transitions, including 19 commonly recurring injustices. We aim to show how when low-carbon transitions unfold, deeper injustices related to equity, distribution, and fairness invariably arise

Global energy governance : a review and research agenda

Over the past few years, global energy governance (GEG) has emerged as a major new field of enquiry in international studies. Scholars engaged in this field seek to understand how the energy sector is governed at the global level, by whom and with what consequences. By focusing on governance, they broaden and enrich the geopolitical and hard-nosed security perspectives that have long been, and still are, the dominant perspectives through which energy is analysed. Though still a nascent field, the literature on GEG is thriving and continues to attract the attention of a growing number of researchers. This article reviews the GEG literature as it has developed over the past 10 years. Our aim is to highlight both the progress and limitations of the field, and to identify some opportunities for future research. The article proceeds as follows. First, it traces the origins of the GEG literature (section “Origins and roots of GEG research”). The subsequent sections deal with the two topics that have received the most attention in the GEG literature: Why does energy need global governance (section “The goals and rationale of global energy governance”)? And, who governs energy (section “Mapping the global energy architecture”)? We then address a third question that has received far less attention: How well or poor is energy governed (section “Evaluating global energy governance”)? In our conclusions (section “Conclusions and outlook”), we reflect on the current state of GEG, review recent trends and innovations, and identify some questions that warrant future consideration by scholars. This article is published as part of a thematic collection on global governance

TRAF6 Promotes Myogenic Differentiation via the TAK1/p38 Mitogen-Activated Protein Kinase and Akt Pathways

p38 mitogen-activated protein kinase (MAPK) is an essential kinase involved in myogenic differentiation. Although many substrates of p38 MAPK have been identified, little is known about its upstream activators during myogenic differentiation. TRAF6 is known to function in cytokine signaling during inflammatory responses. However, not much is known about its role in myogenic differentiation and muscle regeneration. We showed here that TRAF6 and its intrinsic ubiquitin E3 ligase activity are required for myogenic differentiation. In mouse myoblasts, knockdown of TRAF6 compromised the p38 MAPK and Akt pathways, while deliberate activation of either pathway rescued the differentiation defect caused by TRAF6 knockdown. TAK1 acted as a key signal transducer downstream of TRAF6 in myogenic differentiation. In vivo, knockdown of TRAF6 in mouse muscles compromised the injury-induced muscle regeneration without impairing macrophage infiltration and myoblast proliferation. Collectively, we demonstrated that TRAF6 promotes myogenic differentiation and muscle regeneration via the TAK1/p38 MAPK and Akt pathways

Investigation of Cellular and Molecular Responses to Pulsed Focused Ultrasound in a Mouse Model

Continuous focused ultrasound (cFUS) has been widely used for thermal ablation of tissues, relying on continuous exposures to generate temperatures necessary to induce coagulative necrosis. Pulsed FUS (pFUS) employs non-continuous exposures that lower the rate of energy deposition and allow cooling to occur between pulses, thereby minimizing thermal effects and emphasizing effects created by non-thermal mechanisms of FUS (i.e., acoustic radiation forces and acoustic cavitation). pFUS has shown promise for a variety of applications including drug and nanoparticle delivery; however, little is understood about the effects these exposures have on tissue, especially with regard to cellular pro-homing factors (growth factors, cytokines, and cell adhesion molecules). We examined changes in murine hamstring muscle following pFUS or cFUS and demonstrate that pFUS, unlike cFUS, has little effect on the histological integrity of muscle and does not induce cell death. Infiltration of macrophages was observed 3 and 8 days following pFUS or cFUS exposures. pFUS increased expression of several cytokines (e.g., IL-1α, IL-1β, TNFα, INFγ, MIP-1α, MCP-1, and GMCSF) creating a local cytokine gradient on days 0 and 1 post-pFUS that returns to baseline levels by day 3 post-pFUS. pFUS exposures induced upregulation of other signaling molecules (e.g., VEGF, FGF, PlGF, HGF, and SDF-1α) and cell adhesion molecules (e.g., ICAM-1 and VCAM-1) on muscle vasculature. The observed molecular changes in muscle following pFUS may be utilized to target cellular therapies by increasing homing to areas of pathology

Justice from an interdisciplinary perspective: the impact of the revolution in Human Sciences on Peace Research and International Relations

Peace and justice have been a preferred couple in theoretical writings - but what do we know about their empirical relationship? Insights from other disciplines suggest that humans are highly sensitive to violations of justice and that justice concerns permeate social relations. Neuroscientists have located the parts of the brain responsible for negative reactions to violation of claims for justice. Evolutionary biologists have identified rules of distribution and retribution not only in early human societies but among other socially living species as well. Psychologists have observed the emergence of a sense of justice in very early childhood, while behavioral economists have identified behavior of average persons in experiments that deviated significantly from the model of the "economic man" and could only be explained by a sense of justice. The chapter summarizes these findings and outlines their implications for peace research. It highlights the ambivalent nature of justice for social relations. Justice concerns can exacerbate conflicts between individuals and groups but justice can also provide standards for arriving at durable peaceful solutions to conflicts. Understanding these ambivalences and their repercussions for international and intrastate relations provides a promising path towards understanding conflict dynamics

Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing.

Prolonged unaccustomed exercise involving muscle lengthening (eccentric) actions can result in ultrastructural muscle disruption, impaired excitation-contraction coupling, inflammation and muscle protein degradation. This process is associated with delayed onset muscle soreness and is referred to as exercise-induced muscle damage. Although a certain amount of muscle damage may be necessary for adaptation to occur, excessive damage or inadequate recovery from exercise-induced muscle damage can increase injury risk, particularly in older individuals, who experience more damage and require longer to recover from muscle damaging exercise than younger adults. Furthermore, it is apparent that inter-individual variation exists in the response to exercise-induced muscle damage, and there is evidence that genetic variability may play a key role. Although this area of research is in its infancy, certain gene variations, or polymorphisms have been associated with exercise-induced muscle damage (i.e. individuals with certain genotypes experience greater muscle damage, and require longer recovery, following strenuous exercise). These polymorphisms include ACTN3 (R577X, rs1815739), TNF (-308 G>A, rs1800629), IL6 (-174 G>C, rs1800795), and IGF2 (ApaI, 17200 G>A, rs680). Knowing how someone is likely to respond to a particular type of exercise could help coaches/practitioners individualise the exercise training of their athletes/patients, thus maximising recovery and adaptation, while reducing overload-associated injury risk. The purpose of this review is to provide a critical analysis of the literature concerning gene polymorphisms associated with exercise-induced muscle damage, both in young and older individuals, and to highlight the potential mechanisms underpinning these associations, thus providing a better understanding of exercise-induced muscle damage