Changes in the endurance shuttle walk test in COPD patients with chronic respiratory failure after pulmonary rehabilitation: the minimal important difference obtained with anchor- and distribution-based method

Background

Although the endurance shuttle walk test (ESWT) has proven to be responsive to change in exercise capacity after pulmonary rehabilitation (PR) for COPD, the minimally important difference (MID) has not yet been established. We aimed to establish the MID of the ESWT in patients with severe COPD and chronic hypercapnic respiratory failure following PR.

Methods

Data were derived from a randomized controlled trial, investigating the value of noninvasive positive pressure ventilation added to PR. Fifty-five patients with stable COPD, GOLD stage IV, with chronic respiratory failure were included (mean (SD) FEV₁ 31.1 (12.0) % pred, age 62 (9) y). MID estimates of the ESWT in seconds, percentage and meters change were calculated with anchor based and distribution based methods. Six minute walking distance (6MWD), peak work rate on bicycle ergometry (Wpeak) and Chronic Respiratory Questionnaire (CRQ) were used as anchors and Cohen’s effect size was used as distribution based method.

Results

The estimated MID of the ESWT with the different anchors ranged from 186–199 s, 76–82% and 154–164 m. Using the distribution based method the MID was 144 s, 61% and 137 m.

Conclusions

Estimates of the MID for the ESWT after PR showed only small differences using different anchors in patients with COPD and chronic respiratory failure. Therefore we recommend using a range of 186–199 s, 76–82% or 154–164 m as MID of the ESWT in COPD patients with chronic respiratory failure. Further research in larger populations should elucidate whether this cut-off value is also valid in other COPD populations and with other interventions.

Trial registration

ClinicalTrials.Gov (ID {"type":"clinical-trial","attrs":{"text":"NCT00135538","term_id":"NCT00135538"}}NCT00135538).

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-015-0182-x) contains supplementary material, which is available to authorized users.     

Thymoquinone is protective against 2,3,7,8-tetrachlorodibenzo-p-dioxin induced hepatotoxicity

We investigated changes in rat liver tissues following administration of thymoquinone (TQ) against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced hepatotoxicity. Fifty rats were assigned randomly to five groups of 10 as follows: control, corn oil, TCDD, TQ and TCDD + TQ. Biochemical and histopathological analyses were conducted on liver tissue. We found that 30 day TCDD administration caused histopathological changes in liver including thickening of Glisson’s capsule, intracytoplasmic vacuolization in hepatocytes, sinusoidal dilation, vascular and sinusoidal congestion and inflammatory cell infiltration. TCDD administration increased malondialdehyde (MDA), total oxidant status (TOS), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels in rat liver tissue and reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and total antioxidant status (TAS) levels compared to all other groups. In the TQ treated group, GSH, SOD, CAT and TAS levels increased compared to all other groups. MDA, TOS, ALT, AST, ALP levels decreased compared to all other groups. Our histological findings were consistent with the biochemical findings. The oxidative and histologic effects of TCDD were eliminated by TQ treatment. TCDD administration caused oxidative stress in rat liver and TQ administered with TCDD prevented TCDD induced hepatotoxicity. TQ could be considered an alternative anti-TCDD toxicity agent.     

Dynamic receptor team formation can explain the high signal transduction gain in Escherichia coli

Evolution has provided many organisms with sophisticated sensory systems that enable them to respond to signals in their environment. The response frequently involves alteration in the pattern of movement, either by directed movement, a process called taxis, or by altering the speed or frequency of turning, which is called kinesis. Chemokinesis has been most thoroughly studied in the peritrichous bacterium Escherichia coli, which has four helical flagella distributed over the cell surface, and swims by rotating them. When rotated counterclockwise the flagella coalesce into a propulsive bundle, producing a relatively straight "run," and when rotated clockwise they fly apart, resulting in a "tumble" which reorients the cell with little translocation. A stochastic process generates the runs and tumbles, and in a chemoeffector gradient, runs that carry the cell in a favorable direction are extended. The cell senses spatial gradients as temporal changes in receptor occupancy and changes the probability of counterclockwise rotation (the bias) on a fast timescale, but adaptation returns the bias to baseline on a slow timescale, enabling the cell to detect and respond to further concentration changes. The overall structure of the signal transduction pathways is well characterized in E. coli, but important details are still not understood. Only recently has a source of gain in the signal transduction network been identified experimentally, and here we present a mathematical model based on dynamic assembly of receptor teams that can explain this observation.     

Compliance of a cobalt chromium coronary stent alloy – the COVIS trial

Aim

Female cardiac transplant recipients' aerobic capacity is 60% lower than sex and age-predicted values. The effect of exercise training on restoring the impaired aerobic endurance and muscle strength in female cardiac transplant recipients is not known. This study examined the effect that aerobic and strength training have on improving aerobic endurance and muscle strength in female cardiac transplant recipients.

Methods

20 female cardiac transplant recipients (51 ± 11 years) participated in this investigation. The subjects performed a baseline six-minute walk test and a leg-press strength test when they were discharged following cardiac transplantation. The subjects then participated in a 12-week exercise program consisting of aerobic and lower extremity strength training. Baseline assessments were repeated following completion of the exercise intervention.

Results

At baseline, the cardiac transplant recipients' aerobic endurance was 50% lower than age-matched predicted values. The training program resulted in a significant increase in aerobic endurance (pre-training: 322 ± 104 m vs. post-training: 501 ± 99 m, p < 0.05) and leg-press strength (pre-training: 48 ± 16 kg. vs. post-training: 78 ± 27 kg, p < 0.05).

Conclusion

Aerobic and strength training are effective interventions that can partially restore the impaired aerobic endurance and strength found in female cardiac transplant recipients.     

Higher-level snake phylogeny inferred from mitochondrial DNA sequences of 12S rRNA and 16S rRNA genes

Portions of two mitochondrial genes (12S and 16S ribosomal RNA) were sequenced to determine the phylogenetic relationships among the major clades of snakes. Thirty-six species, representing nearly all extant families, were examined and compared with sequences of a tuatara and three families of lizards. Snakes were found to constitute a monophyletic group (confidence probability [CP] = 96%), with the scolecophidians (blind snakes) as the most basal lineages (CP = 99%). This finding supports the hypothesis that snakes underwent a subterranean period early in their evolution. Caenophidians (advanced snakes), excluding Acrochordus, were found to be monophyletic (CP = 99%). Among the caenophidians, viperids were monophyletic (CP = 98%) and formed the sister group to the elapids plus colubrids (CP = 94%). Within the viperids, two monophyletic groups were identified: true vipers (CP = 98%) and pit vipers plus Azemiops (CP = 99%). The elapids plus Atractaspis formed a monophyletic clade (CP = 99%). Within the paraphyletic Colubridae, the largely Holarctic Colubrinae was found to be a monophyletic assemblage (CP = 98%), and the Xenodontinae was found to be polyphyletic (CP = 91%). Monophyly of the henophidians (primitive snakes) was neither supported nor rejected because of the weak resolution of relationships among those taxa, except for the clustering of Calabaria with a uropeltid, Rhinophis (CP = 94%).      

A continuum model for coupled cells

A continuum model of diffusion-coupled cells that more accurately reflects the presence of low-permeability gap junctions between cells is analyzed. It is shown by a multi-scale analysis that to lowest order the slow evolution of the mean concentration is described by the usual ordinary differential equations for a discrete model. Furthermore, stable non-uniform steady solutions are shown to exist in the continuum model of a one component system, whereas this is impossible for the standard reaction-diffusion model of this system. It is also shown how to average the equations in this continuum model to obtain a system of reaction-diffusion equations with constant coefficients.     

Getting in shape and swimming: the role of cortical forces and membrane heterogeneity in eukaryotic cells

Recent research has shown that motile cells can adapt their mode of propulsion to the mechanical properties of the environment in which they find themselves—crawling in some environments while swimming in others. The latter can involve movement by blebbing or other cyclic shape changes, and both highly-simplified and more realistic models of these modes have been studied previously. Herein we study swimming that is driven by membrane tension gradients that arise from flows in the actin cortex underlying the membrane, and does not involve imposed cyclic shape changes. Such gradients can lead to a number of different characteristic cell shapes, and our first objective is to understand how different distributions of membrane tension influence the shape of cells in an inviscid quiescent fluid. We then analyze the effects of spatial variation in other membrane properties, and how they interact with tension gradients to determine the shape. We also study the effect of fluid–cell interactions and show how tension leads to cell movement, how the balance between tension gradients and a variable bending modulus determine the shape and direction of movement, and how the efficiency of movement depends on the properties of the fluid and the distribution of tension and bending modulus in the membrane.

     

A model of calcium dynamics in cardiac myocytes based on the kinetics of ryanodine-sensitive calcium channels.

The ryanodine-sensitive calcium channels are pivotal to signal transduction and cell function in many cell types, including cardiac myocytes. In this paper a kinetic model is proposed for these channels. In the model there are two Ca regulatory sites on the channel protein, one positive and the other negative. Cytoplasmic Ca binds to these regulatory sites independently It is assumed that the binding of Ca to the positive site is a much faster process than binding to the negative site. At steady state, the channel opening as a function of the Ca concentration is a bell-shaped curve. The model predicts the adaptation of channels to constant Ca stimulus. When this model is applied to cardiac myocytes, it predicts excitability with respect to Ca perturbations, smoothly graded responses, and Ca oscillations in certain pathological circumstances. In a spatially distributed system, traveling Ca waves in individual myocytes exist under certain conditions. This model can also be applied to other systems where the ryanodine-sensitive channels have been identified.     

Pattern formation in generalized Turing systems

Turing's model of pattern formation has been extensively studied analytically and numerically, and there is recent experimental evidence that it may apply in certain chemical systems. The model is based on the assumption that all reacting species obey the same type of boundary condition pointwise on the boundary. We call these scalar boundary conditions. Here we study mixed or nonscalar boundary conditions, under which different species satisfy different boundary conditions at any point on the boundary, and show that qualitatively new phenomena arise in this case. For example, we show that there may be multiple solutions at arbitrarily small lengths under mixed boundary conditions, whereas the solution is unique under homogeneous scalar boundary conditions. Moreover, even when the same solution exists under scalar and mixed boundary conditions, its stability may be different in the two cases. We also show that mixed boundary conditions can reduce the sensitivity of patterns to domain changes.Supported in part by NIH Grant # GM29123     

Cyclic AMP oscillations in suspensions of Dictyostelium discoideum

A model developed previously for signal relay and adaptation in the cellular slime mould Dictyostelium discoideum is shown to account for the observed oscillations of calcium and cyclic AMP in cellular suspensions. A qualitative argument is given which explains how the oscillations arise, and numerical computations show how characteristics such as the period and amplitude of the periodic solutions depend on parameters in the model. Several extensions of the basic model are investigated, including the effect of cell aggregation and the effect of time delays in the activation and adaptation processes. The dynamics of mixed cell populations in which only a small fraction of the cells are capable of autonomous oscillation are also studied.