Pre-ejection period by radial artery tonometry supplements echo doppler findings during biventricular pacemaker optimization

Background

Biventricular (Biv) pacemaker echo optimization has been shown to improve cardiac output however is not routinely used due to its complexity. We investigated the role of a simple method involving computerized pre-ejection time (PEP) assessment by radial artery tonometry in guiding Biv pacemaker optimization.

Methods

Blinded echo and radial artery tonometry were performed simultaneously in 37 patients, age 69.1 ± 12.8 years, left ventricular (LV) ejection fraction (EF) 33 ± 10%, during Biv pacemaker optimization. Effect of optimization on echo derived velocity time integral (VTI), ejection time (ET), myocardial performance index (MPI), radial artery tonometry derived PEP and echo-radial artery tonometry derived PEP/VTI and PEP/ET indices was evaluated.

Results

Significant improvement post optimization was achieved in LV ET (286.9 ± 37.3 to 299 ± 34.6 ms, p < 0.001), LV VTI (15.9 ± 4.8 cm to 18.4 ± 5.1 cm, p < 0.001) and MPI (0.57 ± 0.2 to 0.45 ± 0.13, p < 0.001) and in PEP (246.7 ± 36.1 ms to 234.7 ± 35.5 ms, p = 0.003), PEP/ET (0.88 ± 0.21 to 0.79 ± 0.17, p < 0.001), and PEP/VTI (17.3 ± 7 to 13.78 ± 4.7, p < 0.001). The correlation between comprehensive echo Doppler and radial artery tonometry-PEP guided optimal atrioventricular delay (AVD) and optimal interventricular delay (VVD) was 0.75 (p < 0.001) and 0.69 (p < 0.001) respectively. In 29 patients with follow up assessment, New York Heart Association (NYHA) class reduced from 2.5 ± 0.8 to 2.0 ± 0.9 (p = 0.004) at 1.8 ± 1.4 months.

Conclusion

An acute shortening of PEP by radial artery tonometry occurs post Biv pacemaker optimization and correlates with improvement in hemodynamics by echo Doppler and may provide a cost-efficient approach to assist with Biv pacemaker echo optimization.     

Principal trabecular structural orientation predicted by quantitative ultrasound is strongly correlated with \upmu FEA determined anisotropic apparent stiffness

The microarchitecture and alignment of trabecular bone adapts to the particular mechanical milieu applied to it. Due to this anisotropic mechanical property, measurement orientation has to be taken into consideration when assessing trabecular bone quality and fracture risk prediction. Quantitative ultrasound (QUS) has demonstrated the ability in predicting the principal structural orientation (PSO) of trabecular bone. Although the QUS prediction for PSO is very close to that of \(\upmu \) CT, certain angle differences still exist. It remains unknown whether this angle difference can induce significant differences in mechanical properties or not. The objective of this study was to evaluate the mechanical properties in different PSOs predicted using different methods, QUS and \(\upmu \) CT, thus to investigate the ability of QUS as a means to predict the PSO of trabecular bone noninvasively. By validating the ability of QUS to predict the PSO of trabecular bone, it is beneficial for future QUS applications because QUS measurements in the PSO can provide information more correlated with the mechanical properties than with other orientations. In this study, seven trabecular bone balls from distal bovine femurs were used to generate finite element models based on the 3-dimensional \(\upmu \) CT images. Uniaxial compressive loading was performed on the bone ball models in the finite element analysis (FEA) in six different orientations (three anatomical orientations, two PSOs predicted by QUS and the longest vector of mean intercept length (MIL) tensor calculated by \(\upmu \) CT). The stiffness was calculated based on the reaction force of the bone balls under loading, and the von Mises stress results showed that both the mechanical properties in the PSOs predicted by QUS are significantly higher than the anatomical orientations and comparatively close to the longest vector of MIL tensor. The stiffness in the PSOs predicted by QUS is also highly correlated with the stiffness in the MIL tensor orientation (ATTmax vs. MIL, \(R^{2}\)  = 0.98, \(p<001\) ; UVmax vs. MIL, \(R^{2}\)  = 0.92, \(p<001\) ). These results were validated by in vitro mechanical testing on the bone ball samples. This study demonstrates that the PSO of trabecular bone predicted by QUS has an equally strong apparent stiffness with the orientation predicted by \(\upmu \) CT.     

Assessing functional mitral regurgitation with exercise echocardiography: rationale and clinical applications

Background

Strain, and particularly Longitudinal Peak Systolic Strain (LPSS), plays a role in investigating the segmental and overall contractility of the heart which is a particularly interesting feature in athletes in whom regular training determines several morphological and functional modifications in both the ventricles, that normally work at different loads. Speckle tracking techniques assess the LPSS of LV and RV from B-mode imaging in real time, with uniform accuracy in all segments, and can verify the possible dissimilar segmental contributions of the two chambers to overall myocardial contraction. The aim of the study is to quantify the LPSS in real time in both the ventricles in order to estimate any possible different deformation properties in them during a systolic period.

Methods

32 subjects (20 athletes and 18 controls) were submitted to a standard echocardiographic examination at rest and after a Hand Grip (HG) stress. From a four-chamber-view image, the LPSS parameter was measured with Speckle Tracking analysis in the basal and medium-apical segments of the two ventricles, at rest and after HG.

Results

In both athletes and controls, LPSS values were significantly higher in the RV of athletes (RV LPSS^{medium-apical} -23.87 ± 4.94;^{basalfreewall} -25.04 ± 4.12 at rest) and controls (RV LPSS^{medium-apical} -25.21 ± 4.97;^{basalfreewall} -28.69 ± 4.62 at rest) than in the LV of both (athletes LV LPSS^{medium-apical} -18.14 ± 4.16;^{basallateralwall} -16.05 ± 12.32; controls^{medium-apical} -18.81 ± 2.64;^{basallateralwall} -19.74 ± 3.84) With the HG test a significant enhancement of the LPSS(with P <.05) in the medium-apical segments of LV and RV was evident, but only in athletes; there was no modification of the standard echo-parameters in either group.

Conclusion

ST analysis is an easy method for investigating the contractility of the RV through deformation parameters, showing greater involvement of the RV than LV at rest. In athletes only, after isometric stress the two ventricles show particular myocardial deformation properties of the regions around the apex where the curvature of the wall is more marked. The clinical application of this new approach in athletes and normal subjects requires further investigation.     

Release of non-exchangeable {}^{{{\text{15}}}}{\text{NH}}^{{\text{ + }}}_{{\text{4}}} from subgrade, decomposed granite substrates and uptake by non-mycorrhizal and mycorrhizal California native annual grass, Vulpia microstachys

Release rates of recently fixed $ {\text{NH}}^{{\text{ + }}}_{{\text{4}}} $ from non-exchangeable interlayer sites in 2:1 silicate minerals were determined for decomposed granite (DG) saprolites from three locations in California, USA. Recently-fixed $ {\text{NH}}^{{\text{ + }}}_{{\text{4}}} $ release from the DG substrate was quantified by extracting diffused $ {\text{NH}}^{{\text{ + }}}_{{\text{4}}} $ with H-resin, as well as a native, annual grass Vulpia microstachys. The $ {\text{NH}}^{{\text{ + }}}_{{\text{4}}} $ release data varied with via the method of extraction, which included H-resin pre-treatments (Na⁺ or H⁺) and V. microstachys uptake (mycorrhizal inoculated or uninoculated). After 6 weeks (1008 h), more $ {\text{NH}}^{{\text{ + }}}_{{\text{4}}} $ was recovered from fixed interlayer positions by the H-resins as compared to uptake by V. microstachys. The H⁺ treated H-resins recovered more released $ {\text{NH}}^{{\text{ + }}}_{{\text{4}}} $ (≈94 mg ${\text{NH}}^{{\text{ + }}}_{{\text{4}}} - {\text{N}}\;{\text{kg}}^{1} $ or (12%) of total fixed $ {\text{NH}}^{{\text{ + }}}_{{\text{4}}} $ ) in two of the three DG samples as compared to the Na⁺ treated resins, (which recovered ≈70–78 mg ${\text{NH}}^{{\text{ + }}}_{{\text{4}}} - {\text{N}}\;{\text{kg}}^{{{\text{ - 1}}}} $ (or 9–10%) of the total fixed $ {\text{NH}}^{{\text{ + }}}_{{\text{4}}} $ ). The V. microstachys assimilated 8–9% of the total fixed $ {\text{NH}}^{{\text{ + }}}_{{\text{4}}} $ with mycorrhizal inoculum as compared to only 2% without a mycorrhizal inoculum, over the same time period. The fixed $ {\text{NH}}^{{\text{ + }}}_{{\text{4}}} $ release kinetics from the H-resin experiments were most accurately described by first order and power function models, and can be characterized as biphasic using a heterogeneous diffusion model. Uptake of both the ¹⁵N and ambient, unlabelled N from the soils was closely related to plant biomass. There was no significant difference in percent of N per unit of biomass between the control and mycorrhizal treatments. The findings presented here indicate that observed, long-term $ {\text{NH}}^{{\text{ + }}}_{{\text{4}}} $ release rates from DG in studies utilizing resins, may overestimate the levels of fixed $ {\text{NH}}^{{\text{ + }}}_{{\text{4}}} $ made available to plants and microorganisms. Additionally, the study suggested that mycorrhizae facilitate the acquisition and plant uptake of fixed $ {\text{NH}}^{{\text{ + }}}_{{\text{4}}} $ , resulting in markedly increased plant biomass production.     

A thermomechanical framework for reconciling the effects of ultraviolet radiation exposure time and wavelength on connective tissue elasticity

Augmentation of the mechanical properties of connective tissue using ultraviolet (UV) radiation—by targeting collagen cross-linking in the tissue at predetermined UV exposure time \((t)\) and wavelength \((\lambda )\) —has been proposed as a therapeutic method for supporting the treatment for structural-related injuries and pathologies. However, the effects of \(\lambda \) and \(t\) on the tissue elasticity, namely elastic modulus \((E)\) and modulus of resilience \((u_\mathrm{Y})\) , are not entirely clear. We present a thermomechanical framework to reconcile the \(t\) - and \(\lambda \) -related effects on \(E\) and \(u_\mathrm{Y}\) . The framework addresses (1) an energy transfer model to describe the dependence of the absorbed UV photon energy, \(\xi \) , per unit mass of the tissue on \(t\) and \(\lambda \) , (2) an intervening thermodynamic shear-related parameter, \(G\) , to quantify the extent of UV-induced cross-linking in the tissue, (3) a threshold model for the \(G\) versus \(\xi \) relationship, characterized by   \(t_\mathrm{C}\) —the critical \(t\) underpinning the association of \(\xi \) with \(G\) —and (4) the role of \(G\) in the tissue elasticity. We hypothesized that \(G\) regulates \(E\) (UV-stiffening hypothesis) and \(u_\mathrm{Y}\) (UV-resilience hypothesis). The framework was evaluated with the support from data derived from tensile testing on isolated ligament fascicles, treated with two levels of \(\lambda \) (365 and 254 nm) and three levels of \(t\) (15, 30 and 60 min). Predictions from the energy transfer model corroborated the findings from a two-factor analysis of variance of the effects of \(t\) and \(\lambda \) treatments. Student’s t test revealed positive change in \(E\) and \(u_\mathrm{Y}\) with increases in \(G\) —the findings lend support to the hypotheses, implicating the implicit dependence of UV-induced cross-links on \(t\) and \(\lambda \) for directing tissue stiffness and resilience. From a practical perspective, the study is a step in the direction to establish a UV irradiation treatment protocol for effective control of exogenous cross-linking in connective tissues.     

Coronary microcirculatory dysfunction is associated with left ventricular dysfunction during follow-up after STEMI

Background

Coronary microvascular resistance is increased after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI), which may be related in part to changed left ventricular (LV) dynamics. Therefore we studied the coronary microcirculation in relation to systolic and diastolic LV function after STEMI.

Methods

The study cohort consisted of 12 consecutive patients, all treated with primary PCI for a first anterior wall STEMI. At 4 months, we assessed pressure-volume loops. Subsequently, we measured intracoronary pressure and flow velocity and calculated coronary microvascular resistance. Infarct size and LV mass were assessed using magnetic resonance imaging.

Results

Patients with an impaired systolic LV function due to a larger myocardial infarction showed a higher baseline average peak flow velocity (APV) than the other patients (26?±?7 versus 17?±?5 cm/s, p?=?0.003, respectively), and showed an impaired variable microvascular resistance index (2.1?±?1.0 versus 4.1?±?1.3 mmHg?cm^?1?s^?1, p?=?0.003, respectively). Impaired diastolic relaxation time was inversely correlated with hyperaemic APV (r?=??0.56, p?=?0.003) and positively correlated with hyperaemic microvascular resistance (r?=?0.48, p?=?0.01). LV dilatation was associated with a reduced variable microvascular resistance index (r?=?0.78, p?=?0.006).

Conclusion

A larger anterior myocardial infarction results in impaired LV performance associated with reduced coronary microvascular resistance variability, in particular due to higher coronary blood flow at baseline in these compromised left ventricles.     

Plasma and lymphocyte Hsp72 responses to exercise in athletes with prior exertional heat illness

We investigated the effect of exercise in the heat on both intracellular and extracellular Hsp72 in athletes with a prior history of exertional heat illness (EHI). Two groups of runners, one consisting of athletes who had a previous history of EHI, and a control group (CON) of similar age (29.7 ± 1.2 and 29.1 ± 2 years CON vs. EHI) and fitness [maximal oxygen consumption $(\dot V{{\text{O}}_2}\hbox{max} )$ 65.7 ± 2 and 64.5 ± 3 ml kg^?1 min^?1 CON vs. EHI] were recruited. Seven subjects in each group ran on a treadmill for 1 h at 72 % $\dot V{{\text{O}}_2}\hbox{max}$ in warm conditions (30 °C, 40 % RH) reaching rectal temperatures of ~39.3 (CON) and ~39.2 °C (EHI). Blood was collected every 10 min during exercise and plasma was analysed for extracellular Hsp72. Intracellular Hsp72 levels were measured in both monocytes and lymphocytes before and immediately after the 60-min run, and then after 1 h recovery at an ambient temperature of 24 °C. Plasma Hsp72 increased from 1.18 ± 0.14 and 0.86 ± 0.08 ng/ml (CON vs. EHI) at rest to 4.56 ± 0.63 and 4.04 ± 0.45 ng/ml (CON vs. EHI, respectively) at the end of exercise (p < 0.001), with no difference between groups. Lymphocyte Hsp72 was lower in the EHI group at 60 min of exercise (p < 0.05), while monocyte Hsp72 was not different between groups. The results of the present study suggest that the plasma Hsp72 response to exercise in athletes with a prior history of EHI remained similar to that of the CON group, while the lymphocyte Hsp72 response was reduced.     

Diastolic time – frequency relation in the stress echo lab: filling timing and flow at different heart rates

 

A cutaneous force-frequency relation recording system based on first heart sound amplitude vibrations has been recently validated. Second heart sound can be simultaneously recorded in order to quantify both systole and diastole duration.

Aims

1- To assess the feasibility and extra-value of operator-independent, force sensor-based, diastolic time recording during stress.

Methods

We enrolled 161 patients referred for stress echocardiography (exercise 115, dipyridamole 40, pacing 6 patients). The sensor was fastened in the precordial region by a standard ECG electrode. The acceleration signal was converted into digital and recorded together with ECG signal. Both systolic and diastolic times were acquired continuously during stress and were displayed by plotting times vs. heart rate. Diastolic filling rate was calculated as echo-measured mitral filling volume/sensor-monitored diastolic time.

Results

Diastolic time decreased during stress more markedly than systolic time. At peak stress 62 of the 161 pts showed reversal of the systolic/diastolic ratio with the duration of systole longer than diastole. In the exercise group, at 100 bpm HR, systolic/diastolic time ratio was lower in the 17 controls (0.74 ± 0.12) than in patients (0.86 ± 0.10, p < 0.05 vs. controls). Diastolic filling rate increased from 101 ± 36 (rest) to 219 ± 92 ml/m²* s^-1 at peak stress (p < 0.5 vs. rest).

Conclusion

Cardiological systolic and diastolic duration can be monitored during stress by using an acceleration force sensor. Simultaneous calculation of stroke volume allows monitoring diastolic filling rate. Stress-induced "systolic-diastolic mismatch" can be easily quantified and is associated to several cardiac diseases, possibly expanding the spectrum of information obtainable during stress.     

Sensory uncertainty and stick balancing at the fingertip

The effects of sensory input uncertainty, $\varepsilon $ , on the stability of time-delayed human motor control are investigated by calculating the minimum stick length, $\ell _\mathrm{crit}$ , that can be stabilized in the inverted position for a given time delay, $\tau $ . Five control strategies often discussed in the context of human motor control are examined: three time-invariant controllers [proportional–derivative, proportional–derivative–acceleration (PDA), model predictive (MP) controllers] and two time-varying controllers [act-and-wait (AAW) and intermittent predictive controllers]. The uncertainties of the sensory input are modeled as a multiplicative term in the system output. Estimates based on the variability of neural spike trains and neural population responses suggest that $\varepsilon \approx 7$ –13 %. It is found that for this range of uncertainty, a tapped delay-line type of MP controller is the most robust controller. In particular, this controller can stabilize inverted sticks of the length balanced by expert stick balancers (0.25–0.5 m when $\tau \approx 0.08$  s). However, a PDA controller becomes more effective when $\varepsilon > 15\,\%$ . A comparison between $\ell _\mathrm{crit}$ for human stick balancing at the fingertip and balancing on the rubberized surface of a table tennis racket suggest that friction likely plays a role in balance control. Measurements of $\ell _\mathrm{crit},\,\tau $ , and a variability of the fluctuations in the vertical displacement angle, an estimate of $\varepsilon $ , may make it possible to study the changes in control strategy as motor skill develops.     

Impact of the papillary muscles on cardiac magnetic resonance image analysis of important left ventricular parameters in hypertrophic cardiomyopathy

Purpose

The use of cardiac magnetic resonance (CMR) analysis has increased in patients with hypertrophic cardiomyopathy (HCM). Quantification of left ventricular (LV) measures will be affected by the inclusion or exclusion of the papillary muscles as part of the LV mass, but the magnitude of effect and potential consequences are unknown.

Methods

We performed Cine-CMR in (1) clinical HCM patients (n?=?55) and (2) subclinical HCM mutation carriers without hypertrophy (n?=?14). Absolute and relative differences in LV ejection fraction (EF) and mass were assessed between algorithms with and without inclusion of the papillary muscles.

Results

Papillary muscle mass in group 1 was 6.6?±?2.5 g/m² and inclusion of the papillary muscles resulted in significant relative increases in LVEF of 4.5?±?1.8?% and in LV mass of 8.7?±?2.6?%. For group 2 these figures were 4.0?±?0.9 g/m², 3.8?±?1.0?% and 9.5?±?1.8?%, respectively. With a coefficient of variation of 4?%, this 9?% difference in LV mass during CMR follow-up will be considered a change, while in fact the exact same mass may have been assessed according to two different algorithms.

Conclusions

In clinical HCM patients, CMR quantification of important LV measures is significantly affected by inclusion or exclusion of the papillary muscles. In relative terms, the difference was similar in subjects without hypertrophy. This underscores a general need for a uniform approach in CMR image analysis.

     

Age,smoking habits,heat stress,and their interactive effects with carbon monoxide and peroxyacetylnitrate on man's aerobic power

Metabolic, body temperature, and cardiorespiratory responses of 16 healthy middle-aged (40–57 years) men, 9 nonsmokers and 7 smokers, were obtained during tests of maximal aerobic power at ambient environmental temperatures of 25 ± 0.5 and 35 ± 0.5°C and 20% relative humidity under four conditions: (a) filtered air, FA; (b) 50 ppm carbon monoxide in filtered air, CO; (c) 0.27 ppm peroxyacetylnitrate in filtered air, PAN; and (d) a combination of all three mixtures, PANCO. There was no significant change in maximum aerobic power \(\left( {\dot VO2max} \right)\) related to the presence of air pollutants, although total working time was lowered in the 25°C environment while breathing CO. Older nonsmokers did have a decrement in \(\left( {\dot VO2max} \right)\) while breathing 50 ppm CO, while older smokers failed to show any change. This difference was related to the initial COHb levels of the smokers, who, when breathing this level of ambient CO, had only a 14% increase in COHb over their initial levels in contrast to the 200% increase in the nonsmokers. Smoking habits were the most influential factor affecting the cardiorespiratory responses of these older men to maximal exercise. Regardless of ambient conditions, smokers had a significantly lower (27%) aerobic power than nonsmokers, were breathing closer to their maximal breathing capacities throughout the walk, and had a higher respiratory exchange ratio. While the \(\left( {\dot VO2max} \right)\) of nonsmokers was only 6% less than that of younger nonsmoking males ( \(\bar x\) age = 25 years) working under similar conditions, the aerobic power of the older smokers was 26% lower than that of young smokers ( \(\bar x\) age = 24 years).     

Muscle GSH-Px activity after prolonged exercise,training, and selenium supplementation

A double-blind study of the effects of supplementing with selenium vs. placebo on the physiological responses to acute and chronic exercise was conducted in 24 healthy, nonsmoking males, mean age 22.9±2.1 yr, randomly divided into two groups of 12 (Pla/Sel). After a controlled period in the absence of training, all subjects were put on an individualized endurance training program with the same rules of progression and overload (3 sessions/wk×10 wk). Supplementation, either real (240 μg of organic selenium/d in Sel group) or imaginary (Pla group) was administered during the same period. In each of the conditions Pre- and Post- (training ± sel supplementation), muscle, plasma, and systemic parameters were determined before (BF) and after (AF) acute exercise, involving the repetition of muscle work cycles separated by 5-min recovery periods, combining 20 min at 65% and a maximal duration of 100% VO₂ max of running on a treadmill, leading the subjects to exhaustion between 2 h 40 min and 3 h 30 min. Changes in parameters as a function of three independent variables:

1. Acute exercise (E);
2. Chronic exercise (T); and
3. Selenium supplementing (S)

were tested with ANOVA and the Student\rsst-test on paired series. Among the variables examined, muscle glutathione peroxidase (GPx) presented a remarkable behavior. Enzymatic activity:

1. Decreased significantly (p<0.05,n=24) between the beginning and the end of acute exercise: 29.6±12 vs. 20.8±8.1 IU·g protein^?1 in Pre conditions;
2. Remained at the same level in resting conditions between the beginning and end of training (from Pre to Post) regardless of the group: 33.5±10.8 vs. 32.3±19.8 and 25.7±12.4 vs. 23.5±10.2 IU·g protein^?1 in Pla and Sel subjects, respectively; and
3. Increased from 23.5±10.2 to 37.3±28.5 (P=0.057) during acute exercise in Post-conditions (after training) in supplemented subjects (Sel group).

The situation was as if acute exercise played the role of allosteric stimulator of the GPx reaction in muscle.     

Basic Features of a Cell Electroporation Model: Illustrative Behavior for Two Very Different Pulses

Science increasingly involves complex modeling. Here we describe a model for cell electroporation in which membrane properties are dynamically modified by poration. Spatial scales range from cell membrane thickness (5 nm) to a typical mammalian cell radius (10  \(\upmu\) m), and can be used with idealized and experimental pulse waveforms. The model consists of traditional passive components and additional active components representing nonequilibrium processes. Model responses include measurable quantities: transmembrane voltage, membrane electrical conductance, and solute transport rates and amounts for the representative “long” and “short” pulses. The long pulse—1.5 kV/cm, 100  \(\upmu\) s—evolves two pore subpopulations with a valley at \({\sim}\) 5 nm, which separates the subpopulations that have peaks at \({\sim}\) 1.5 and \({\sim}\) 12 nm radius. Such pulses are widely used in biological research, biotechnology, and medicine, including cancer therapy by drug delivery and nonthermal physical tumor ablation by causing necrosis. The short pulse—40 kV/cm, 10 ns—creates 80-fold more pores, all small ( \(<\) 3 nm; \(\sim\) 1 nm peak). These nanosecond pulses ablate tumors by apoptosis. We demonstrate the model’s responses by illustrative electrical and poration behavior, and transport of calcein and propidium. We then identify extensions for expanding modeling capability. Structure-function results from MD can allow extrapolations that bring response specificity to cell membranes based on their lipid composition. After a pulse, changes in pore energy landscape can be included over seconds to minutes, by mechanisms such as cell swelling and pulse-induced chemical reactions that slowly alter pore behavior.     

Effects of negative air ions on oxygen uptake kinetics,recovery and performance in exercise: a randomized,double-blinded study

Limited research has suggested that acute exposure to negatively charged ions may enhance cardio-respiratory function, aerobic metabolism and recovery following exercise. To test the physiological effects of negatively charged air ions, 14 trained males (age: 32?±?7 years; \( \overset{\cdotp }{V}{\mathrm{O}}_{2 \max } \) : 57?±?7 mL min^?1 kg^?1) were exposed for 20 min to either a high-concentration of air ions (ION: 220?±?30?×?10³ ions cm^?3) or normal room conditions (PLA: 0.1?±?0.06?×?10³ ions cm^?3) in an ionization chamber in a double-blinded, randomized order, prior to performing: (1) a bout of severe-intensity cycling exercise for determining the time constant of the phase II \( \overset{\cdotp }{V}{\mathrm{O}}_2 \) response (τ) and the magnitude of the \( \overset{\cdotp }{V}{\mathrm{O}}_2 \) slow component (SC); and (2) a 30-s Wingate test that was preceded by three 30-s Wingate tests to measure plasma [adrenaline] (ADR), [nor-adrenaline] (N-ADR) and blood [lactate] (B_Lac) over 20 min during recovery in the ionization chamber. There was no difference between ION and PLA for the phase II \( \overset{\cdotp }{V}{\mathrm{O}}_2 \) τ (32?±?14 s vs. 32?±?14 s; P?=?0.7) or \( \overset{\cdotp }{V}{\mathrm{O}}_2 \) SC (404?±?214 mL vs 482?±?217 mL; P?=?0.17). No differences between ION and PLA were observed at any time-point for ADR, N-ADR and B_Lac as well as on peak and mean power output during the Wingate tests (all P?>?0.05). A high-concentration of negatively charged air ions had no effect on aerobic metabolism during severe-intensity exercise or on performance or the recovery of the adrenergic and metabolic responses after repeated-sprint exercise in trained athletes.     

Integrating qPLM and biomechanical test data with an anisotropic fiber distribution model and predictions of TGF-\upbeta 1 and IGF-1 regulation of articular cartilage fiber modulus

A continuum mixture model with distinct collagen (COL) and glycosaminoglycan elastic constituents was developed for the solid matrix of immature bovine articular cartilage. A continuous COL fiber volume fraction distribution function and a true COL fiber elastic modulus ( $E^\mathrm{f})$ were used. Quantitative polarized light microscopy (qPLM) methods were developed to account for the relatively high cell density of immature articular cartilage and used with a novel algorithm that constructs a 3D distribution function from 2D qPLM data. For specimens untreated and cultured in vitro, most model parameters were specified from qPLM analysis and biochemical assay results; consequently, $E^\mathrm{f}$ was predicted using an optimization to measured mechanical properties in uniaxial tension and unconfined compression. Analysis of qPLM data revealed a highly anisotropic fiber distribution, with principal fiber orientation parallel to the surface layer. For untreated samples, predicted $E^\mathrm{f}$ values were 175 and 422 MPa for superficial (S) and middle (M) zone layers, respectively. TGF- $\upbeta $ 1 treatment was predicted to increase and decrease $E^\mathrm{f}$ values for the S and M layers to 281 and 309 MPa, respectively. IGF-1 treatment was predicted to decrease $E^\mathrm{f}$ values for the S and M layers to 22 and 26 MPa, respectively. A novel finding was that distinct native depth-dependent fiber modulus properties were modulated to nearly homogeneous values by TGF- $\upbeta $ 1 and IGF-1 treatments, with modulated values strongly dependent on treatment.     

Bayesian estimation of genetic parameters for growth,stem straightness,and survival in Eucalyptus globulus on an Andean Foothill site

Knowledge of the genetic variation of key economic traits in Eucalyptus globulus under cold conditions is crucial to the genetic improvement of environmental tolerances and other economic traits. A Bayesian analysis of genetic parameters for quantitative traits was carried out in 37 E. globulus open-pollinated families under cold conditions in southern Chile. The trial is located in the Andean foothills, in the Province of Bío-Bío. The Bayesian approach was performed using Gibbs sampling algorithm. Multi-trait linear and threshold models were fitted to phenotypic data (growth traits, survival, and stem straightness). Fifteen years after planting, height, diameter at breast height, and stem volume were found to be weakly to moderately heritable with Bayesian credible intervals (probability of 90 %): $ {\widehat{h}}^2 $ ?=?0.009–0.102, $ {\widehat{h}}^2 $ ?=?0.031–0.185, and $ {\widehat{h}}^2 $ ?=?0.045–0.205, respectively. Stem straightness was found to be weakly to moderately heritable ranging from 0.032 to 0.208 (Bayesian 90 % credible interval); posterior mode $ {\widehat{h}}^2 $ ?=?0.091. Tree survival at age of 15 years was high in the trial (84.8 %) with such heritability values ranging from 0.072 to 0.157. Survival was non-significantly genetically correlated to growth and stem straightness. Stem volume had the highest predicted genetic gains ranging from 17.9 to 23.7 % (selection rate of 15.8 and 8.3 %, respectively). The results of this study confirm the potential for selective breeding of this eucalypt in areas of southern Chile where cold is a significant constraint.     

Nitric Oxide Donors Augment Interleukin-1β-Induced Vascular Endothelial Growth Factor in Airway Smooth Muscle Cells

Angiogenesis and microvascular leakage are features of chronic inflammatory diseases of which molecular mechanisms are poorly understood. We investigated the effects of interleukin-1β (IL-1β) on the expression and secretion of vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) in porcine airway smooth muscle cells (PASMC) in relation to a nitric oxide (NO) pathway. Serum-deprived (48 h) PASMC were stimulated with IL-1β alone or with NO donor, l-arginine and/or NO synthase inhibitor l-NAME for 4 and 24 h. IL-1β did not affect PlGF release, but augmented VEGF release (2.4-fold) after 24 h. VEGF release was inhibited by l-NAME (531.8 ± 52 pg/ml), but restored and further elevated by l-arginine (1,529 ± 287 pg/ml). IL-1β up-regulated VEGF mRNA (1.8-fold) and this response was attenuated by l-NAME (1.1-fold) and augmented by l-arginine (3.8-fold) at 4 h. Restoration of a NO pathway by l-arginine in l-NAME-treated cells resulted in elevated VEGF mRNA levels (2.2-fold). [³H]Thymidine incorporation assay revealed enhanced porcine pulmonary artery endothelial cell proliferation in response to IL-1β, VEGF and PlGF, and this mitogenic effect was not influenced via the NO pathway. Our results suggest that a NO pathway modulates VEGF synthesis during inflammation contributing to bronchial angiogenesis and vascular leakage.     

Provenance variation and genetic parameters of Eucalyptus viminalis in Argentina

Genetic parameters for growth, stem straightness, pilodyn penetration, relative bark thickness and survival were estimated in a base-population of five open-pollinated provenance/progeny trials of Eucalyptus viminalis. The trials, located in northern, central and southern Buenos Aires Province, Argentina, comprised 148 open-pollinated families from 13 Australian native provenances and eight local Argentinean seedlots. The Australian native provenances come from a limited range of the natural distribution. Overall survival, based on the latest assessment of each trial, was 62.4%. Single-site analyses showed that statistically significant provenances differences (p?<?0.05) for at least one of the studied traits in three out of the five trials analyzed. The local land race performed inconsistently in this study. The average narrow-sense individual-tree heritability estimate $ \left( {{{\hat{h}}^2}} \right) $ was 0.27 for diameter and 0.17 for total height. Values of $ {\hat{h}^2} $ also increased with age. Pilodyn penetration, assessed at only one site, was more heritable $ \left( {{{\hat{h}}^2} = 0.32} \right) $ than the average of growth traits. Estimated individual-tree heritabilities were moderate to low for stem straightness (average of 0.20) and relative bark thickness (0.16). The estimated additive genetic correlations $ \left( {{{{r}}_{{A}}}} \right) $ between diameter and height were consistently high and positive ( $ {{r}_{^A}} $ average of 0.90). High additive genetic correlations were observed between growth variables and pilodyn penetration ( $ {{r}_{^A}} $ average of 0.58). Relative bark thickness showed a negative correlation with diameter $ \left( {{{{r}}_{^A}} = - 0.39} \right) $ and height $ \left( {{{{r}}_{^A}} = - 0.51} \right) $ . The average estimated additive genetic correlation between sites was high for diameter (0.67). The implications of all these parameter estimates for genetic improvement of E. viminalis in Argentina are discussed.     

Kinetic models of coupling between H+ and Na+-translocation and ATP synthesis/hydrolysis by F0F1-ATPases: Can a cell utilize both\Delta \bar \mu _{H^ + } and\Delta \bar \mu _{Na^ + } for ATP synthesis underin vivo conditions using the same enzyme?

Kinetic models of the F₀F₁-ATPase able to transport H⁺ or/and Na⁺ ions are proposed. It is assumed that (i) H⁺ and Na⁺ compete for the same binding sites, (ii) ion translocation through F₀ is coupled to the rate-limiting step of the F₁-catalyzed reaction. The main characteristics of the dependences of ATP synthesis and hydrolysis rates on Δφ, ΔpH, and ΔpNa are predicted for various versions of the coupling model. The mechanism of the switchover from \(\Delta \bar \mu _{H^ + } \) -dependent synthesis to the \(\Delta \bar \mu _{Na^ + } \) -dependent one is demonstrated. It is shown that even with a drastic drop in \(\Delta \bar \mu _{H^ + } \) , ATP hydrolysis by the proton mode of catalysis can be effectively inhibited by Δφ and ΔpNa. The results obtained strongly support the possibility that the same F₀F₁-ATPase in bacterial cells can utilize both \(\Delta \bar \mu _{H^ + } \) and \(\Delta \bar \mu _{Na^ + } \) for ATP synthesis underin vivo conditions.