Quantifying fractal dynamics of human respiration: age and gender effects

We sought to quantify the fractal scaling properties of human respiratory dynamics and determine whether they are altered with healthy aging and gender. Continuous respiratory datasets (obtained by inductive plethysmography) were collected from 40 healthy adults (10 young men, 10 young women, 10 elderly men, and 10 elderly women) during 120 min of spontaneous breathing. The interbreath interval (IBI) time series were extracted by a new algorithm and fractal scaling exponents that quantify power-law correlations were computed using detrended fluctuation analysis. Under supine, resting, and spontaneous breathing conditions, both healthy young and elderly subjects had scaling exponents for the IBI time series that indicate long-range (fractal) correlations across multiple time scales. Furthermore, the scaling exponents (mean ± SD) for the IBI time series were significantly (p < 0.03) lower (indicating decreased correlations) in the healthy elderly male 0.60 ± 0.08) compared to the young male (0.68 ± 0.07), young female (0.70 ± 0.07), and elderly female (0.67 ± 0.06) subjects. These results provide evidence for fractal organization in physiologic human breathing cycle dynamics, and for their degradation in elderly men. These findings may have implications for modeling integrated respiratory control mechanisms, quantifying their changes in aging or disease, and assessing the outcome of interventions aimed toward restoring normal physiologic respiratory dynamics. © 2002 Biomedical Engineering Society. PAC2002: 8719Uv, 8710+e, 0545Df     

Repeated apneas do not affect the hypercapnic ventilatory response in the short term

Long-term training of breath-hold diving reduces the hypercapnic ventilatory response (HCVR), an index of the CO₂ sensitivity. The aim of the present study was to elucidate whether also short-term apnea training (repeating apneas with short intervals) reduces the HCVR, thereby being one contributing factor explaining the progressively increasing breath-holding time (BHT) with repetition of apneas. Fourteen healthy volunteers performed a series of five maximal-duration apneas with face immersion and two measurements of the HCVR, using the Read rebreathing method. The BHT increased by 43% during the series of apneas (P < 0.001). However, the slope of the HCVR test was not affected by the series of apneas, being 2.52 (SD 1.27) and 2.24 (SD 1.14) l min⁻¹ mmHg⁻¹ in the control test and in the test performed within 2 min after the last apnea of the series, respectively (NS). Thus, a change in the HCVR cannot explain the observed short-term training effect on BHT.     

Late Na+ current produced by human cardiac Na+ channel isoform Nav1.5 is modulated by its β1 subunit

Experimental data accumulated over the past decade show the emerging importance of the late sodium current (I _NaL) for the function of both normal and, especially, failing myocardium, in which I _NaL is reportedly increased. While recent molecular studies identified the cardiac Na⁺ channel (NaCh) α subunit isoform (Na_v1.5) as a major contributor to I _NaL, the molecular mechanisms underlying alterations of I _NaL in heart failure (HF) are still unknown. Here we tested the hypothesis that I _NaL is modulated by the NaCh auxiliary β subunits. tsA201 cells were transfected simultaneously with human Na_v1.5 (former hH1a) and cardiac β₁ or β₂ subunits, and whole-cell patch-clamp experiments were performed. We found that I _NaL decay kinetics were significantly slower in cells expressing α + β₁ (time constant τ = 0.73 ± 0.16 s, n = 14, mean ± SEM, P < 0.05) but remained unchanged in cells expressing α + β₂ (τ = 0.52 ± 0.09 s, n = 5), compared with cells expressing Na_v1.5 alone (τ = 0.54 ± 0.09 s, n = 20). Also, β₁, but not β₂, dramatically increased I _NaL relative to the maximum peak current, I _NaT (2.3 ± 0.48%, n = 14 vs. 0.48 ± 0.07%, n = 6, P < 0.05, respectively) and produced a rightward shift of the steady-state availability curve. We conclude that the auxiliary β₁ subunit modulates I _NaL, produced by the human cardiac Na⁺ channel Na_v1.5 by slowing its decay and increasing I _NaL amplitude relative to I _NaT. Because expression of Na_v1.5 reportedly decreases but β₁ remains unchanged in chronic HF, the relatively higher expression of β₁ may contribute to the known I _NaL increase in HF via the modulation mechanism found in this study. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

The gastric HK-ATPase: structure, function, and inhibition

The gastric H,K-ATPase, a member of the P₂-type ATPase family, is the integral membrane protein responsible for gastric acid secretion. It is an α,β-heterodimeric enzyme that exchanges cytoplasmic hydronium with extracellular potassium. The catalytic α subunit has ten transmembrane segments with a cluster of intramembranal carboxylic amino acids located in the middle of the transmembrane segments TM4, TM5,TM6, and TM8. Comparison to the known structure of the SERCA pump, mutagenesis, and molecular modeling has identified these as constituents of the ion binding domain. The β subunit has one transmembrane segment with N terminus in cytoplasmic region. The extracellular domain of the β subunit contains six or seven N-linked glycosylation sites. N-glycosylation is important for the enzyme assembly, maturation, and sorting. The enzyme pumps acid by a series of conformational changes from an E₁ (ion site in) to an E₂ (ion site out) configuration following binding of MgATP and phosphorylation. Several experimental observations support the hypothesis that expulsion of the proton at 160 mM (pH 0.8) results from movement of lysine 791 into the ion binding site in the E₂P configuration. Potassium access from the lumen depends on activation of a K and Cl conductance via a KCNQ1/KCNE2 complex and Clic6. K movement through the luminal channel in E₂P is proposed to displace the lysine along with dephosphorylation to return the enzyme to the E₁ configuration. This enzyme is inhibited by the unique proton pump inhibitor class of drug, allowing therapy of acid-related diseases.     

Allometric scaling of strength measurements to body size

For comparative purposes, normalisation of strength measures to body size using allometric scaling is recommended. A wide range of scaling exponents have been suggested, typically utilising body mass, although a comprehensive evaluation of different body size variables has not been documented. Differences between force (F) and torque (T) measurements of strength, and the velocity of measurement might also explain some of the variability in the scaling exponents proposed. Knee extensor strength of 86 young men was assessed with measurement of torque at four velocities (0–4.19 rad s⁻¹) and force measured isometrically. Body size variables included body mass, height and fat-free mass. Scaling exponents for torque were consistently higher than for force, but the velocity of torque measurement had no influence. As the confounding effects of fat mass were restricted, scaling exponents and the strength of the power-function relationships progressively increased. Fat-free mass determined a surprisingly high proportion of the variance in measured strength (F, 31%; T, 52–58%). Absolute force and torque measurements, and even torque normalised for body mass, were significantly influenced by height, although strength measures normalised to fat-free mass were not. To normalise strength measurements to body mass, for relatively homogenous lean populations (body fat <20%), exponents of 0.66 (F) and 1.0 (T) are appropriate. For more adipose populations (body fat >20%) lower body mass exponents appear more suitable (F, 0.45; T, 0.68). Nevertheless, fat-free mass is the recommended index for scaling strength to body size, and higher exponents (F, 0.76; T, 1.12) are advocated in this case.     

Insertion of α1S II–III loop and C terminal sequences into α1H fails to restore excitation–contraction coupling in dysgenic myotubes

The L-type Ca²⁺ channel in skeletal muscle (α_1S) is essential for excitation–contraction (EC) coupling. Previous studies using chimeras composed of α_1S together with α_1C or α_1M demonstrated the importance of the α_1S II–III loop and of a smaller subdomain (residues 720–764; ‘ECC’) in skeletal EC coupling. However, these chimeras failed to test the significance of regions outside the II–III loop, which are highly conserved between α_1S and α_1C. Therefore, we have injected dysgenic (α_1S-lacking) myotubes with cDNAs encoding chimeras between α_1S and the highly divergent T-type Ca²⁺ channel, α_1H. The chimeras consisted of GFP-tagged α_1H with one or more of the following substitutions: α_1S II–III loop residues 720–764 (‘ECC’), a putative targeting domain of the α_1S C terminus (‘target’; residues 1543–1662) or the entire α_1S C terminus (‘Cterm’; residues 1382–1873). The presence of either target or Cterm affected the expression and/or kinetics of whole-cell currents recorded from both dysgenic muscle cells and tsa-201 cells. Importantly, substitution of ECC alone into GFP-α_1H (GFP-α_1H + ECC), or together with either target (GFP-α_1H + ECC + target) or Cterm (GFP-α_1H + ECC + Cterm ), was insufficient to restore electrically evoked contractions. Depolarization-induced fluorescence transients for GFP-α_1H + ECC, GFP-α_1H + ECC + target or GFP-α_1H + ECC + Cterm had a bell shaped dependence upon membrane voltage (inconsistent with skeletal EC coupling) and were also exceedingly small (unlike cardiac EC coupling). The absence of EC coupling for these chimeras raises the possibility that regions of α_1S outside of ECC and target are necessary for providing the context that allows these two domains to function in EC coupling and targeting, respectively. Additionally, an inadequate membrane density of the chimeras may have contributed to the lack of coupling. This revised version was published online in July 2006 with corrections to the Cover Date.     

Effects of the essential oils of Lippia turbinata and Lippia polystachya (Verbenaceae) on the temporal pattern of locomotion of the mosquito Culex quinquefasciatus (Diptera: Culicidae) larvae

The essential oils (EO) of Lippia turbinata (TUR) and Lippia polystachya (POL) have shown lethal effects against mosquito larvae. The present work evaluated whether these EO at doses ranging from sublethal to lethal (20, 40 and 80 ppm) modify the temporal pattern of locomotion of Culex quinquefasciatus larvae. Larvae were individually placed in glass boxes, and their activity recorded at 0.3 s intervals during 40 min. Individuals treated with doses >40 ppm of either EO significantly decreased their ambulation speed and the percentage of total time ambulating compared to controls. TUR 80 ppm decreased their ambulation even sooner than POL 80 ppm, when compared to their respective controls. These findings are consistent with the neurotoxic effect against insects attributed to α-Thujone, a main component of both EO. A detrended fluctuation fractal analysis evaluating the complexity and organisation of the temporal pattern of locomotion showed fractal patterns in all animals. Both sublethal and lethal doses of TUR and POL increased the complexity of ambulation. Interestingly, for POL 20 ppm, an increase in complexity was observed, while no changes in general activity were detected, suggesting that fractal analysis may be more sensitive to detect behavioural changes than general activity evaluation.     

Localization of N-type Ca2+ channels in the rat spinal cord following chronic constrictive nerve injury

Previous studies have shown that spinal L-type, N-type, and P-type Ca²⁺-channel blockers are effective in modulating pain behavior caused nerve injury. In the present work, using the loose ligation of the sciatic nerve model, we characterized the time course of the appearance of tactile and cold allodynia and the corresponding spinal expression of the N-type Ca²⁺ channel α_1B-subunit after nerve ligation. Within 1 week after ligation, the majority of rats developed a unilateral sensitivity to mechanical stimulation (von Frey filaments), as well as sensitivity to cold, which persisted for 30 days. Immunocytochemical analysis of the spinal cord in sham-operated animals for the α_1B-subunit showed a smooth, moderate staining pattern in the superficial laminae I–II, as well as in ventral α-motoneurons. In nerve-ligated animals, an intense, dot-like immunoreactivity in the ipsilateral dorsal horn was observed from 5–20 days after nerve ligation. The most prominent α_1B-subunit upregulation was found in the outer as well as the inner part of lamina II (II_o, II_i), extending from the medial toward the lateral region of the L4 and L5 spinal segments. The behavioral changes which developed after chronic constriction injury directly correlated with the α_1B-subunit upregulation in the corresponding spinal cord segments. These data suggest that upregulation of the spinal α_1B-subunit may play an important role in the initiation and maintenance of pain state after peripheral nerve injury. Electronic Publication     

Voronoi Polyhedra Analysis of Optimized Arterial Tree Models

Topological and metric properties of Voronoi polyhedra (VP) generated by the distal end points of terminal segments in arterial tree models grown by the method of constrained constructive optimization (CCO) are analyzed with the aim to characterize the spatial distribution of their supply sites relative to randomly distributed points as a reference model. The distributions of the number N _f of Voronoi cell faces, cell volume V, surface area S, area A of individual cell faces, and asphericity parameter of the CCO models are all significantly different from the ones of random points, whereas the distributions of V, S, and are also significantly different among CCO models optimized for minimum intravascular volume and minimum segment length (p < 0.0001). The distributions of N _f , V, and S of the CCO models are reasonably well approximated by two-parameter gamma distributions. We study scaling of intravascular blood volume and arterial cross-sectional area with the volume of supplied tissue, the latter being represented by the VP of the respective terminal segments. We observe scaling exponents from 1.20 ± 0.007 to 1.08 ± 0.005 for intravascular blood volume and 0.77 ± 0.01 for arterial cross-sectional area. Setting terminal flows proportional to the associated VP volumes during tree construction yields a relative dispersion of terminal flows of 37% and a coefficient of skewness of 1.12. © 2003 Biomedical Engineering Society. PAC2003: 8719Uv, 8710+e, 4720Ky, 0260Pn, 0230Oz     

The role of tropomyosin isoforms and phosphorylation in force generation in thin-filament reconstituted bovine cardiac muscle fibres

The thin filament extraction and reconstitution protocol was used to investigate the functional roles of tropomyosin (Tm) isoforms and phosphorylation in bovine myocardium. The thin filament was extracted by gelsolin, reconstituted with G-actin, and further reconstituted with cardiac troponin together with one of three Tm varieties: phosphorylated αTm (αTm.P), dephosphorylated αTm (αTm.deP), and dephosphorylated βTm (βTm.deP). The effects of Ca, phosphate, MgATP and MgADP concentrations were examined in the reconstituted fibres at pH 7.0 and 25°C. Our data show that Ca²⁺ sensitivity (pCa₅₀: half saturation point) was increased by 0.19 ± 0.07 units when βTm.deP was used instead of αTm.deP (P < 0.05), and by 0.27 ± 0.06 units when phosphorylated αTm was used (P < 0.005). The cooperativity (Hill factor) decreased (but insignificantly) from 3.2 ± 0.3 (5) to 2.8 ± 0.2 (7) with phosphorylation. The cooperativity decreased significantly from 3.2 ± 0.3 (5) to 2.1 ± 0.2 (9) with isoform change from αTm.deP to βTm.deP. There was no significant difference in isometric tension or stiffness between αTm.P, αTm.deP, and βTm.deP muscle fibres at saturating [Ca²⁺] or after rigor induction. Based on the six-state cross-bridge model, sinusoidal analysis indicated that the equilibrium constants of elementary steps differed up to 1.7× between αTm.deP and βTm.deP, and up to 2.0× between αTm.deP and αTm.P. The rate constants differed up to 1.5× between αTm.deP and βTm.deP, and up to 2.4× between αTm.deP and αTm.P. We conclude that tension and stiffness per cross-bridge are not significantly different among the three muscle models.     

Cleavage of endogenous γENaC and elevated abundance of αENaC are associated with increased Na⁺ transport in response to apical fluid volume expansion in human H441 airway epithelial cells

Using human H441 airway epithelial cells cultured at air–liquid interface (ALI), we have uniquely correlated the functional response to apical fluid volume expansion with the abundance and cleavage of endogenous α- and γENaC proteins in the apical membrane. Monolayers cultured at ALI rapidly elevated I _sc when inserted into fluid-filled Ussing chambers. The increase in I _sc was not significantly augmented by the apical addition of trypsin, and elevation was abolished by the protease inhibitor aprotinin and an inhibitor of the proprotein convertase, furin. These treatments also increased the IC₅₀ amiloride indicating that the effect was via inhibition of highly Na⁺-selective ENaC channels. Apical fluid, 5–500 μl for 1 h in culture, increased the spontaneous starting I _sc in a dose-dependent manner, whilst maximal fluid-induced I _sc in the Ussing chamber was unchanged. Apical fluid expansion increased the abundance of 63–65-kDa αENaC proteins in the apical membrane. However, this could not be attributed to increased cleavage as protease inhibitors had no effect on the ratio of cleaved to non-cleaved (90 kDa) αENaC proteins. Instead, fluid expansion increased αENaC abundance in the membrane. In contrast, function correlated well with γENaC cleavage at known sites by furin and extracellular proteases. Interestingly, cleavage of γENaC was associated with increased retrieval from the membrane via the proteosomal pathway. Thus, the response to apical fluid volume expansion in H441 airway epithelial cells involves cleavage of γENaC, and changes in α- and γENaC protein abundance at the apical membrane.     

Delayed effect of blood pressure fluctuations on heart rate in patients with end-stage kidney disease

The time delay of the baroreflex may be affected by decreased autonomic activity in uremia. To assess the magnitude and the time delay of heart rate response in patients with end-stage renal disease, continuous beat-to-beat intervals (IBI) and systolic blood pressure (SBP) recordings were monitored in hemodialysis (HD) patients (n = 72), in patients after renal transplantation (TX) (n = 41) and in age-matched controls (C) (n = 34). A 2-term prediction model was computed, in which each IBI change was represented as a function of SBP difference values of two immediately preceding beats. Baroreflex slope and the frequency domain variables low frequency (LF) α index, phase shift, and lag time were also calculated. b ₁ coefficient, representing the dependence of IBI difference with the first previous SBP difference was lower in HD than in Cs, but increased after TX. b ₁ correlated with age, baroreflex slope, and LF α, and b ₂ (the 2nd term), with both the phase shift between SBP and IBI and lag time. The latter was lower in Cs than in HD or transplanted patients. These findings show that the time delay of the heart rate response to SBP variations is increased in renal insufficiency. The prolonged delay may contribute to the circulatory instability in uremic patients.     

High mobility group box protein-1 correlates with microinflammatory state and nutritional status in continuous ambulatory peritoneal dialysis patients

High mobility group box protein-1 (HMGB-1) was recently identified as a new type of inflammatory cytokine. Inflammation can lead to malnutrition to some extent. Our study was aimed to clarify the relationship between serum HMGB-1 level with microinflammatory state and nutritional status in continuous ambulatory peritoneal dialysis (CAPD) patients. Patients in the treatment of maintenance of peritoneal dialysis for >6 months were included. HMGB-1, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). High-sensitivity C-reactive-protein (hs-CRP), prealbumin (PA), serum albumin (S-Alb), hemoglobin (Hb), subjective global nutritional assessment (SGA), and CAPD presents’ urea clearance rate (Kt/V), creatinine clearance (CrCl), residual glomerular filtration rate (rGFR), and dialysate-to-plasma ratio of creatinine after 4 h (D/P_4Cr) were analyzed. The Independent-samples t test and Pearson’s rank correlation test were used. Serum HMGB-1, IL-6, and TNF-α of CAPD patients were significantly higher than in the control group (P < 0.05); Serum HMGB-1 levels had positive relationships with TNF-α (r = 0.730, P < 0.01), hs-CRP (r = 0.361, P < 0.01), and IL-6 (r = 0.865, P < 0.01), and had negative relationships with Hb (r = −0.59, P < 0.01), Alb (r = −0.34, P < 0.05), and PA (r = −0.44, P < 0.01); no significant relationships were found between serum HMGB-1 with SGA, peritoneal dialysis age, Kt/V, CrCl, rGFR, and D/P_4Cr. Our study revealed that HMGB-1 was elevated significantly in CAPD patients and correlated with indicators of inflammation and malnutrition. Serum HMGB-1 could be used as a marker for evaluating inflammation and malnutrition in CAPD patients.     

Helicobacter pylori induces the release of α-defensin by human granulocytes

Objectives:  Little information is available on the potential role of α-defensins derived from neutrophils during H. pylori infection, or the effect of H. pylori on the α-defensin release. The effects of H. pylori on human granulocytes were investigated in vitro by flow cytometry and ELISA. Additionally we sought to identify by immunohistochemistry the α-defensins within the gastric mucosa of patients infected with H. pylori. Materials and Methods:  The intracellular expression of α-defensin in human granulocytes and in mononuclear cells was determined by flow cytometry. Induction of α-defensin release from granulocytes, mononuclear cells, or from whole blood cultures by H. pylori was detected by measuring the HNP1-3 (α-defensin) concentrations in the supernatants by ELISA. Immunohistochemistry was used to identify HNP1-3 in infiltrating neutrophils in the gastric mucosa of eight patients. Results:  A considerable intracellular α-defensin staining was observed in granulocytes. Stimulation of granulocytes with H. pylori resulted in a decrease in intracellular staining which was due to the extracellular release of α-defensin. In whole blood cultures H. pylori infection resulted in significantly high α-defensin concentrations (131623 ± 13986 pg/ml), which were mainly due to the activity of the granulocytes with only a minor amount furnished by the mononuclear cells. In H. pylori-infected mucosa, infiltrating neutrophils showed intense immunostaining with anti-HNP1-3. The intensity of α-defensin staining varied parallel with the density of H. pylori in the biopsy samples. Conclusions:  H. pylori induce α-defensin release from granulocytes which may well be important in local host response to H. pylori infection in gastroduodenal diseases. Received 19 May 2008; returned for revision 20 October 2008; received from final revision 28 October 2008; accepted by I. Ahnfelt-R?nne 23 November 2008     

Hepatoprotective Effect of Infliximab,an Anti-TNF-α Agent,on Carbon Tetrachloride-Induced Hepatic Fibrosis

To assess the effect of infliximab, an anti-tumor necrosis factor (TNF)-α agent, on the carbon tetrachloride (CCl₄)-induced hepatic fibrosis in rats. Rats were randomized into three groups (n = 9). The control group received only intraperitoneal (i.p.) olive oil. Hepatic fibrosis was induced by repeated i.p. injections of 1.5 ml/kg CCl₄ (1:3 mixture with olive oil) for 5 weeks in the remaining two groups which were also injected subcutaneous saline or 2 mg/kg infliximab. Infliximab reduced the levels of aspartate aminotransferase and alanine aminotransferase (p < 0.05 for both). The scores of hepatic necrosis, inflammation and fibrosis, and expression of α-smooth muscle actin were lower in the infliximab-treated group than the CCI₄-treated group (p < 0.01, p < 0.001, p < 0.01, p < 0.001, respectively). However, there was no significant difference in terms of liver tissue and plasma malondialdehyde, and serum TNF-α levels, while infliximab relatively reduced the level of transforming growth factor-β₁ (373.0 ± 153.1 vs. 280.8 ± 127.1 pg/ml). Treatment with infliximab attenuated the necro-inflammation and fibrogenesis in the CCI₄-induced hepatic fibrosis, and thus it might be effective as a therapeutic anti-fibrotic agent.     

Effects of 6 weeks of n-3 fatty acids and antioxidant mixture on lipid peroxidation at rest and postexercise

The purpose of this randomized study was to measure the influence of 6 weeks of LCPUFA (600 mg EPA and 400 mg DHA per day) supplementation alone or in association with 30 mg vitamin E, 60 mg vitamin C and 6 mg β-carotene on resting and exercise-induced lipid peroxidation in judoists (n = 36). Blood samples were collected at rest before (T ₁) and after the supplementation period, in preexercise (T ₂) and postexercise (T ₃) conditions, for analysis of α-tocopherol, retinol, lag phase (Lp) before free radical-induced oxidation, maximum rate of oxidation (R _max) during the propagating chain reaction, maximum amount of conjugated dienes (CD_max) accumulated after the propagation phase, and nitric oxide, malondialdehyde and lipoperoxide (POOL) concentrations. Dietary data were collected using a 7-day diet record. There were no significant differences among treatment groups with respect to habitual intakes of energy from fat, carbohydrate, or protein. At T ₁, there were no significant differences among treatment groups with respect to lipid peroxidation, lag phase, and levels of α-tocopherol or retinol. The consumption of an n-3 LC PUFA supplement increased oxidative stress at rest and did not attenuate the exercise-induced oxidative stress. The addition of antioxidants did not prevent the formation of oxidation products at rest. On the contrary, it seems that the combination of antioxidants added to the n-3 LCPUFA supplement led to a decrease in, CD_max, R _max, and POOL and MDA concentrations after a judo training session.     

Sensitivity of local dynamic stability of over-ground walking to balance impairment due to galvanic vestibular stimulation

Impaired balance control during gait can be detected by local dynamic stability measures. For clinical applications, the use of a treadmill may be limiting. Therefore, the aim of this study was to test sensitivity of these stability measures collected during short episodes of over-ground walking by comparing normal to impaired balance control. Galvanic vestibular stimulation (GVS) was used to impair balance control in 12 healthy adults, while walking up and down a 10 m hallway. Trunk kinematics, collected by an inertial sensor, were divided into episodes of one stroll along the hallway. Local dynamic stability was quantified using short-term Lyapunov exponents (λ_s), and subjected to a bootstrap analysis to determine the effects of number of episodes analysed on precision and sensitivity of the measure. λ_s increased from 0.50 ± 0.06 to 0.56 ± 0.08 (p = 0.0045) when walking with GVS. With increasing number of episodes, coefficients of variation decreased from 10 ± 1.3% to 5 ± 0.7% and the number of p values >0.05 from 42 to 3.5%, indicating that both precision of estimates of λ_s and sensitivity to the effect of GVS increased. λ_s calculated over multiple episodes of over-ground walking appears to be a suitable measure to calculate local dynamic stability on group level.