Ventilation distribution in rats : part 2 – a comparison of electrical impedance tomography and hyperpolarised helium magnetic resonance imaging

Background: Hyperpolarised helium MRI (He3 MRI) is a new technique that enables imaging of the air distribution within the lungs. This allows accurate determination of the ventilation distribution in vivo. The technique has the disadvantages of requiring an expensive helium isotope, complex apparatus and moving the patient to a compatible MRI scanner. Electrical impedance tomography (EIT) a non-invasive bedside technique that allows constant monitoring of lung impedance, which is dependent on changes in air space capacity in the lung. We have used He3MRI measurements of ventilation distribution as the gold standard for assessment of EIT. Methods: Seven rats were ventilated in supine, prone, left and right lateral position with 70% helium/30% oxygen for EIT measurements and pure helium for He3 MRI. The same ventilator and settings were used for both measurements. Image dimensions, geometric centre and global in homogeneity index were calculated. Results: EIT images were smaller and of lower resolution and contained less anatomical detail than those from He3 MRI. However, both methods could measure positional induced changes in lung ventilation, as assessed by the geometric centre. The global in homogeneity index were comparable between the techniques. Conclusion: EIT is a suitable technique for monitoring ventilation distribution and inhomgeneity as assessed by comparison with He3 MRI.

Biomechanics of synthetic elastin : insights from Magnetic Resonance microimaging

We used Magnetic Resonance microimaging (μMRI) to study the compressive behaviour of synthetic elastin. Compression-induced changes in the elastin sample were quantified using longitudinal and transverse spin relaxation rates (R1 and R2, respectively). Spatially-resolved maps of each spin relaxation rate were obtained, allowing the heterogeneous texture of the sample to be observed with and without compression. Compression resulted in an increase of both the mean R1 and the mean R2, but most of this increase was due to sub-locations that exhibited relatively low R1 and R2 in the uncompressed state. This behaviour can be described by differential compression, where local domains in the hydrogel with a relatively low biopolymer content compress more than those with a relatively high biopolymer content.

Diurnal variation of ocular biometrics under natural and defocused conditions

It is well known that a broad range of ocular anatomical and physiological parameters undergo significant diurnal variation. However, the natural diurnal variations that occur in the length of the human eye (axial length) and their underlying causes have been less well studied. Improvements in optical methods for the measurement of ocular biometrics now allow more precise and comprehensive measurements of axial length to be performed than has previously been possible. Research from animal models also suggests a link between diurnal axial length variations and longer term myopic eye growth, and that retinal image defocus can disrupt these diurnal rhythms in axial length. This research programme has examined the diurnal variations in axial length in young normal eyes, the contributing components and the influence of optical stimuli on these changes. In the first experiment, the normal pattern and consistency of the diurnal variations in axial length were examined at 10 different times (5 measurements each day, at ~ 3-hour intervals from ~ 9 am to ~ 9 pm) over 2 consecutive days on 30 young adult subjects (15 myopes, 15 emmetropes). Additionally, variations in a range of other ocular biometric measurements such as choroidal thickness, intraocular pressure, and other ocular biometrics were also explored as potential factors that may be associated with the observed variations in axial length. To investigate the potential influence of refractive error on diurnal axial length variations, the differences in the magnitude and pattern of diurnal variations in axial length between the myopic and emmetropic subjects were examined. Axial length underwent significant diurnal variation that was consistently observed over the 2 consecutive days of measurements, with the longest axial length typically occurring during the day, and the shortest at night. Significant diurnal variations were also observed in choroidal thickness, IOP and other ocular biometrics (such as central corneal thickness, anterior chamber depth and vitreous chamber depth) of the eye. Diurnal variations in vitreous chamber depth, IOP (positive associations) and choroidal thickness (negative association) were all significantly correlated with the diurnal changes in axial length. Choroidal thickness was found to fluctuate approximately in antiphase to the axial length changes, with the average timing of the longest axial length coinciding with the thinnest choroid and vice versa. There were no significant differences in the ocular diurnal variations associated with refractive error. Given that the diurnal changes in axial length could be associated with the changes in the eye’s optical quality, whether the optical quality of the eye also undergoes diurnal variation in the same cohort of young adult myopes and emmetropes over 2 consecutive days was also examined. Significant diurnal variations were observed only in the best sphere refraction (power vector M) and in the spherical aberration of the eye over two consecutive days of testing. The changes in the eyes lower and higher order ocular optics were not significantly associated with the diurnal variations in axial length and the other measured ocular biometric parameters. No significant differences were observed in the magnitude and timing of diurnal variations in lower-order and higher-order optics associated with refractive error. Since the small natural fluctuations in the eye’s optical quality did not appear to be sufficient to influence the natural diurnal fluctuations in ocular biometric parameters, in the next experiment, the influence of monocular myopic defocus (+1.50 DS) upon the normal diurnal variations in axial length and choroidal thickness of young adult emmetropic human subjects (n=13) imposed over a 12 hour period was examined. A series of axial length and choroidal thickness measurements (collected at ~3 hourly intervals, with the first measurement at ~9 am and the final measurement at ~9 pm) were obtained over three consecutive days. The natural diurnal rhythms (Day 1, no defocus), diurnal rhythms with monocular myopic defocus (Day 2, +1.50 DS spectacle lens over the right eye), and the recovery from any defocus induced changes (Day 3, no defocus) were examined. Significant diurnal variations over the course of the day were observed in both axial length and choroidal thickness on each of the three measurement days. The introduction of monocular myopic defocus led to significant reductions in the mean amplitude of diurnal change, and phase shifts in the peak timing of the diurnal rhythms in axial length and choroidal thickness. These defocus induced changes were found to be transient in nature and returned to normal the day following removal of the defocus. To further investigate the influence of optical stimuli on human diurnal rhythms, in the final experiment, the influence of monocular hyperopic defocus on the normal diurnal rhythms in axial length and choroidal thickness was examined in young adult emmetropic subjects (n=15). Similar to the previous experiment, the natural diurnal rhythms (Day 1, no defocus), diurnal rhythms with monocular hyperopic defocus (Day 2, -2.00 DS spectacle lens over the right eye), and the recovery from any defocus induced changes (Day 3, no defocus) were examined over three consecutive days. Both axial length and choroidal thickness underwent significant diurnal variations on each of the three days. The introduction of monocular hyperopic defocus resulted in a significant increase in the amplitude of diurnal change, but no change in the peak timing of diurnal rhythms in both parameters. The ocular changes associated with hyperopic defocus returned to normal, the day following removal of the defocus. This research has shown that axial length undergoes significant diurnal variation in young adult human eyes, and has shown that the natural diurnal variations in choroidal thickness and IOP are significantly associated, and may underlie these diurnal fluctuations in axial length. This work also demonstrated for the first time that exposing young human eyes to monocular myopic and hyperopic defocus leads to a significant disruption in the normal diurnal rhythms of axial length and choroidal thickness. These changes in axial length with defocus may reflect underlying mechanisms in the human eye that are involved in the regulation of longer term eye growth.

Cardiac parasympathetic reactivation following exercise : implications for training prescription

The objective of exercise training is to initiate desirable physiological adaptations that ultimately enhance physical work capacity. Optimal training prescription requires an individualized approach, with an appropriate balance of training stimulus and recovery and optimal periodization. Recovery from exercise involves integrated physiological responses. The cardiovascular system plays a fundamental role in facilitating many of these responses, including thermoregulation and delivery/removal of nutrients and waste products. As a marker of cardiovascular recovery, cardiac parasympathetic reactivation following a training session is highly individualized. It appears to parallel the acute/intermediate recovery of the thermoregulatory and vascular systems, as described by the supercompensation theory. The physiological mechanisms underlying cardiac parasympathetic reactivation are not completely understood. However, changes in cardiac autonomic activity may provide a proxy measure of the changes in autonomic input into organs and (by default) the blood flow requirements to restore homeostasis. Metaboreflex stimulation (e.g. muscle and blood acidosis) is likely a key determinant of parasympathetic reactivation in the short term (0–90 min post-exercise), whereas baroreflex stimulation (e.g. exercise-induced changes in plasma volume) probably mediates parasympathetic reactivation in the intermediate term (1–48 h post-exercise). Cardiac parasympathetic reactivation does not appear to coincide with the recovery of all physiological systems (e.g. energy stores or the neuromuscular system). However, this may reflect the limited data currently available on parasympathetic reactivation following strength/resistance-based exercise of variable intensity. In this review, we quantitatively analyse post-exercise cardiac parasympathetic reactivation in athletes and healthy individuals following aerobic exercise, with respect to exercise intensity and duration, and fitness/training status. Our results demonstrate that the time required for complete cardiac autonomic recovery after a single aerobic-based training session is up to 24 h following low-intensity exercise, 24–48 h following threshold-intensity exercise and at least 48 h following high-intensity exercise. Based on limited data, exercise duration is unlikely to be the greatest determinant of cardiac parasympathetic reactivation. Cardiac autonomic recovery occurs more rapidly in individuals with greater aerobic fitness. Our data lend support to the concept that in conjunction with daily training logs, data on cardiac parasympathetic activity are useful for individualizing training programmes. In the final sections of this review, we provide recommendations for structuring training microcycles with reference to cardiac parasympathetic recovery kinetics. Ultimately, coaches should structure training programmes tailored to the unique recovery kinetics of each individual.

T helper cell cytokine profiles following endurance exercise

Endurance exercise can cause immunosuppression and increase the risk of upper respiratory illness. The present study examined changes in the secretion of T helper (Th) cell cytokines after endurance exercise. Ten highly trained road cyclists [mean±SEM: age 24.2±1.7 years; height 1.82±0.02 m; body mass 73.8±2.0 kg; peak oxygen uptake 65.9±2.3 mL/(kg•min)] performed 2 h of cycling exercise at 90% of the second ventilatory threshold. Peripheral blood mononuclear cells were isolated and stimulated with phytohemagglutinin. Plasma cortisol concentrations and the concentration of Th1/Th2/Th17 cell cytokines were examined. Data were analyzed using both traditional statistics and magnitude-based inferences. Results revealed a significant decrease in plasma cortisol at 4–24 h postexercise compared with pre-exercise values. Qualitative analysis revealed postexercise changes in concentrations of plasma cortisol, IL-2, TNF, IL-4, IL-6, IL-10, and IL-17A compared with pre-exercise values. A Th1/Th2 shift was evident immediately postexercise. Furthermore, for multiple cytokines, including IL-2 and TNF (Th1), IL-6 and IL-10 (Th2), and IL-17 (Th17), no meaningful change in concentration occurred until more than 4 h postexercise, highlighting the duration of exercise-induced changes in immune function. These results demonstrate the importance of considering “clinically” significant versus statistically significant changes in immune cell function after exercise.

Effects of short-duration and long-duration exercise on lipoprotein(a)

Purpose Most studies that use either a single exercise session, exercise training, or a cross-sectional design have failed to find a relationship between exercise and plasma lipoprotein(a) [Lp(a)] concentrations. However, a few studies investigating the effects of longer and/or more strenuous exercise have shown elevated Lp(a) concentrations, possibly as an acute-phase reactant to muscle damage. Based on the assumption that greater muscle damage would occur with exercise of longer duration, the purpose of the present study was to determine whether exercise of longer duration would increase Lp(a) concentration and creatine kinase. (CK) activity more than exercise of shorter duration. Methods Ten endurance-trained men (mean +/- SD: age, 27 +/- 6 yr; maximal oxygen consumption [(V)over dotO(2max)], 57 +/- 7 mL(.)kg(-1) min(-1)) completed two separate exercise sessions at 70% (V)over dotO(2max). One session required 900 kcal of energy expenditure (60 +/- 6 min), and the other required 1500 kcal (112 +/- 12 min). Fasted blood samples were taken immediately before (0-pre), immediately after (0-post), 1 d after (1-post), and 2 d after (2-post) each exercise session. Results CK activity increased after both exercise sessions (mean +/- SE; 800 kcal: 0-pre 55 +/- 11, 1-post 168 +/- 64 U(.)L(-1.)min(-1); 1500 kcal: 0-pre 51 +/- 5, 1-post 187 +/- 30, 2-post 123 +/- 19 U(.)L(-1.)min(-1); P < 0.05). However, median Lp(a) concentrations were not altered by either exercise session (800 kcal: 0-pre 5.0 mg(.)dL(-1), 0-post 3.2 mg(.)dL(-1), 1-post 4.0 mg(.)dL(-1), 2-post 3.4 mg(.)dL(-1); 1500 kcal: 0-pre 5.8 mg(.)dL(-1), 0-post 4.3 mg(.)dL(-1), 1-post 3.2 mg(.)dL(-1), 2-post 5.3 mg(.)dL(-1)). In addition, no relationship existed between exercise-induced changes in CK activity and Lp(a) concentration (800 kcal: r = -0.26; 1500 kcal: r = -0.02). Conclusion These results suggest that plasma Lp(a) concentration will not increase in response to minor exercise-induced muscle damage in endurance-trained runners.

No indications of persistent oxidative stress in response to an ironman triathlon

Introduction: Training for and competing in ultraendurance exercise events is associated with an improvement in endogenous antioxidant defenses as well as increased oxidative stress. However, consequences on health are currently unclear. Purpose: We aimed to examine the impact of training- and acute exercise-induced changes in the antioxidant capacity on the oxidant/antioxidant balance after an ironman triathlon and whether there are indications for sustained oxidative damage. Methods: Blood samples were taken from 42 well-trained male triathletes 2 d before an ironman triathlon, then immediately postrace, 1, 5, and 19 d later. Blood was analyzed for conjugated dienes (CD), malondialdehyde (MDA), oxidized low-density lipoprotein (oxLDL), oxLDL:LDL ratio, advanced oxidation protein products (AOPP), AOPP:total protein (TP) ratio, Trolox equivalent antioxidant capacity (TEAC), uric acid (UA) in plasma, and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in erythrocytes. Results: Immediately postrace, there were significant increases in CD, AOPP, TEAC, UA (for all P < 0.001), and AOPP:TP (P < 0.01). MDA rose significantly (P < 0.01) 1 d postrace, whereas CD (P < 0.01), AOPP (P = 0.01), AOPP:TP (P < 0.05), and TEAC (P < 0.001) remained elevated. OxLDL:LDL trended to increase, whereas oxLDL significantly (P < 0.01) decreased 1 d postrace. Except for GSH-Px (P = 0.08), activities of SOD (P < 0.001) and CAT (P < 0.05) significantly decreased postrace. All oxidative stress markers had returned to prerace values 5 d postrace. Furthermore, several relationships between training status and oxidative stress markers, TEAC, and antioxidant enzyme activities were noted. Conclusions: This study indicates that despite a temporary increase in most (but not all) oxidative stress markers, there is no persistent oxidative stress in response to an ironman triathlon, probably due to training- and exercise-induced protective alterations in the antioxidant defense system.

Antioxidant responses to an acute ultra-endurance exercise: Impact on DNA stability and indications for an increased need for nutritive antioxidants in the early recovery phase

Antioxidant requirements have neither been defined for endurance nor been defined for ultra-endurance athletes. To verify whether an acute bout of ultra-endurance exercise modifies the need for nutritive antioxidants, we aimed (1) to investigate the changes of endogenous and exogenous antioxidants in response to an Ironman triathlon; (2) to particularise the relevance of antioxidant responses to the indices of oxidatively damaged blood lipids, blood cell compounds and lymphocyte DNA and (3) to examine whether potential time-points of increased susceptibility to oxidative damage are associated with alterations in the antioxidant status. Blood that was collected from forty-two well-trained male athletes 2 d pre-race, immediately post-race, and 1, 5 and 19 d later was sampled. The key findings of the present study are as follows: (1) Immediately post-race, vitamin C, alpha-tocopherol, and levels of the Trolox equivalent antioxidant capacity, the ferric reducing ability of plasma and the oxygen radical absorbance capacity (ORAC) assays increased significantly. Exercise-induced changes in the plasma antioxidant capacity were associated with changes in uric acid, bilirubin and vitamin C. (2) Significant inverse correlations between ORAC levels and indices of oxidatively damaged DNA immediately and 1 d post-race suggest a protective role of the acute antioxidant responses in DNA stability. (3) Significant decreases in carotenoids and gamma-tocopherol 1 d post-race indicate that the antioxidant intake during the first 24 h of recovery following an acute ultra-endurance exercise requires specific attention. Furthermore, the present study illustrates the importance of a diversified and well-balanced diet to maintain a physiological antioxidant status in ultra-endurance athletes in reference to recommendations.

Nanostructured hydroxyapatite surfaces-mediated adsorption alters recognition of BMP receptor IA and bioactivity of bone morphogenetic protein-2

Highly efficient loading of bone morphogenetic protein-2 (BMP-2) onto carriers with desirable performance is still a major challenge in the field of bone regeneration. Till now, the nanoscaled surface-induced changes of the structure and bioactivity of BMP-2 remains poorly understood. Here, the effect of nanoscaled surface on the adsorption and bioactivity of BMP-2 was investigated with a series of hydroxyapatite surfaces (HAPs): HAP crystal-coated surface (HAP), HAP crystal-coated polished surface (HAP-Pol), and sintered HAP crystal-coated surface (HAP-Sin). The adsorption dynamics of recombinant human BMP-2 (rhBMP-2) and the accessibility of the binding epitopes of adsorbed rhBMP-2 for BMP receptors (BMPRs) were examined by a quartz crystal microbalance with dissipation. Moreover, the bioactivity of adsorbed rhBMP-2 and the BMP-induced Smad signaling were investigated with C2C12 model cells. A noticeably high mass-uptake of rhBMP-2 and enhanced recognition of BMPR-IA to adsorbed rhBMP-2 were found on the HAP-Pol surface. For the rhBMP-2-adsorbed HAPs, both ALP activity and Smad signaling increased in the order of HAP-Sin < HAP < HAP-Pol. Furthermore, hybrid molecular dynamics and steered molecular dynamics simulations validated that BMP-2 tightly anchored on the HAP-Pol surface with a relative loosened conformation, but the HAP-Sin surface induced a compact conformation of BMP-2. In conclusion, the nanostructured HAPs can modulate the way of adsorption of rhBMP-2, and thus the recognition of BMPR-IA and the bioactivity of rhBMP-2. These findings can provide insightful suggestions for the future design and fabrication of rhBMP-2-based scaffolds/implants.

The inferior whorl for detecting diabetic peripheral neuropathy using corneal confocal microscopy

PURPOSE: In vivo corneal confocal microscopy (CCM) is increasingly used as a surrogate endpoint in studies of diabetic polyneuropathy (DPN). However, it is not clear whether imaging the central cornea provides optimal diagnostic utility for DPN. Therefore, we compared nerve morphology in the central cornea and the inferior whorl, a more distal and densely innervated area located inferior and nasal to the central cornea. METHODS: A total of 53 subjects with type 1/type 2 diabetes and 15 age-matched control subjects underwent detailed assessment of neuropathic symptoms (NPS), deficits (neuropathy disability score [NDS]), quantitative sensory testing (vibration perception threshold [VPT], cold and warm threshold [CT/WT], and cold- and heat-induced pain [CIP/HIP]), and electrophysiology (sural and peroneal nerve conduction velocity [SSNCV/PMNCV], and sural and peroneal nerve amplitude [SSNA/PMNA]) to diagnose patients with (DPN+) and without (DPN-) neuropathy. Corneal nerve fiber density (CNFD) and length (CNFL) in the central cornea, and inferior whorl length (IWL) were quantified. RESULTS: Comparing control subjects to DPN- and DPN+ patients, there was a significant increase in NDS (0 vs. 2.6 ± 2.3 vs. 3.3 ± 2.7, P < 0.01), VPT (V; 5.4 ± 3.0 vs. 10.6 ± 10.3 vs. 17.7 ± 11.8, P < 0.01), WT (°C; 37.7 ± 3.5 vs. 39.1 ± 5.1 vs. 41.7 ± 4.7, P < 0.05), and a significant decrease in SSNCV (m/s; 50.2 ± 5.4 vs. 48.4 ± 5.0 vs. 39.5 ± 10.6, P < 0.05), CNFD (fibers/mm2; 37.8 ± 4.9 vs. 29.7 ± 7.7 vs. 27.1 ± 9.9, P < 0.01), CNFL (mm/mm2; 27.5 ± 3.6 vs. 24.4 ± 7.8 vs. 20.7 ± 7.1, P < 0.01), and IWL (mm/mm2; 35.1 ± 6.5 vs. 26.2 ± 10.5 vs. 23.6 ± 11.4, P < 0.05). For the diagnosis of DPN, CNFD, CNFL, and IWL achieved an area under the curve (AUC) of 0.75, 0.74, and 0.70, respectively, and a combination of IWL-CNFD achieved an AUC of 0.76. CONCLUSIONS: The parameters of CNFD, CNFL, and IWL have a comparable ability to diagnose patients with DPN. However, IWL detects an abnormality even in patients without DPN. Combining IWL with CNFD may improve the diagnostic performance of CCM.

Foreign aid, domestic investment and welfare

This paper examines the welfare implications of temporary foreign aid in a simple two-period, two-country model of trade. Domestic investment is endogenous, providing an important link between aid in period one and the terms of trade in periods one and two. Transfer-induced changes in the terms of trade redistribute present and future income between the donor and the recipient. In the presence of barriers to international borrowing and lending, such redistribution gives rise to the possibility of temporary aid being both potentially and strictly Pareto improving.

Characterization of anomalous relaxation using the time-fractional Bloch equation and multiple echo T2 *-weighted magnetic resonance imaging at 7T

PURPOSE To study the utility of fractional calculus in modeling gradient-recalled echo MRI signal decay in the normal human brain. METHODS We solved analytically the extended time-fractional Bloch equations resulting in five model parameters, namely, the amplitude, relaxation rate, order of the time-fractional derivative, frequency shift, and constant offset. Voxel-level temporal fitting of the MRI signal was performed using the classical monoexponential model, a previously developed anomalous relaxation model, and using our extended time-fractional relaxation model. Nine brain regions segmented from multiple echo gradient-recalled echo 7 Tesla MRI data acquired from five participants were then used to investigate the characteristics of the extended time-fractional model parameters. RESULTS We found that the extended time-fractional model is able to fit the experimental data with smaller mean squared error than the classical monoexponential relaxation model and the anomalous relaxation model, which do not account for frequency shift. CONCLUSIONS We were able to fit multiple echo time MRI data with high accuracy using the developed model. Parameters of the model likely capture information on microstructural and susceptibility-induced changes in the human brain.

Preventing physical activity induced heat illness in school settings

The climatic conditions of tropical and subtropical regions within Australia present, at times, extreme risk of physical activity induced heat illness. Many administrators and teachers in school settings are aware of the general risks of heat related illness. In the absence of reliable information applied at the local level, there is a risk that inappropriate decisions may be made concerning school events that incorporate opportunities to be physically active. Such events may be prematurely cancelled resulting in the loss of necessary time for physical activity. Under high or extremely high risk conditions however, the absence of appropriate modifications or continuation could place the health of students, staff and other parties at risk. School staff and other key stakeholders should understand the mechanisms of escalating risk and be supported to undertake action to reduce the level of risk through appropriate policies, procedures, resources and action plans.

Distribution of benefits of irrigation induced technological changes and commodity markets : new evidence

A plethora of literature exists on irrigation development. However, only a few studies analyse the distributional issues associated with irrigation induced technological changes (IITC) in the context of commodity markets. Furthermore, these studies deal with only the theoretical arguments and to date no proper investigation has been conducted to examine the long-term benefits of adopting modern irrigation technology. This study investigates the long-term benefit changes of irrigation induced technological changes using data from Sri Lanka with reference to rice farming. The results show that (1) adopting modern technology on irrigation increases the overall social welfare through consumption of a larger quantity at a lower cost (2) the magnitude, sensitivity and distributional gains depend on the price elasticity of demand and supply as well as the size of the marketable surplus (3) non-farm sector gains are larger than farm sector gains (4) the distribution of the benefits among different types of producers depend on the magnitude of the expansion of the irrigated areas as well as the competition faced by traditional farmers (5) selective technological adoption and subsidies have a detrimental effect on the welfare of other producers who do not enjoy the same benefits (6) the short-term distributional effects are more severe than the long-term effects among different groups of farmers.