Analysis of impulse oscillometric measures of lung function and respiratory system model parameters in small airway-impaired and healthy children over a 2-year period

Background

Is Impulse Oscillometry System (IOS) a valuable tool to measure respiratory system function in Children?Asthma (A) is the most prevalent chronic respiratory disease in children. Therefore, early and accurate assessment of respiratory function is of tremendous clinical interest in diagnosis, monitoring and treatment of respiratory conditions in this subpopulation.IOS has been successfully used to measure lung function in children with a high degree of sensitivity and specificity to small airway impairments (SAI) and asthma. IOS measures of airway function and equivalent electrical circuit models of the human respiratory system have been developed to quantify the severity of these conditions. Previously, we have evaluated several known respiratory models based on the Mead's model and more parsimonious versions based on fitting IOS data known as extended RIC (eRIC) and augmented RIC (aRIC) models have emerged, which offer advantages over earlier models.

Methods

IOS data from twenty-six children were collected and compared during pre-bronchodilation (pre-B) and post- bronchodilation (post-B) conditions over a period of 2 years.

Results and Discussion

Are the IOS and model parameters capable of differentiating between healthy children and children with respiratory system distress?Children were classified into two main categories: Healthy (H) and Small Airway-Impaired (SAI). The IOS measures and respiratory model parameters analyzed differed consistently between H and SAI children. SAI children showed smaller trend of "growth" and larger trend of bronchodilator responses than H children.The two model parameters: peripheral compliance (Cp) and peripheral resistance (Rp) tracked IOS indices of small airway function well. Cp was a more sensitive index than Rp. Both eRIC and aRIC Cps and the IOS Reactance Area, AX, (also known as the "Goldman Triangle") showed good correlations.

Conclusions

What are the most useful IOS and model parameters?In this work we demonstrate that IOS parameters such as resistance at 5 Hz (R5), frequency-dependence of resistance (fdR: R5-R20), reactance area (AX), and parameter estimates of respiratory system such as Cp and Rp provide sensitive indicators of lung function and have the capacity to differentiate between obstructed and non-obstructed airway conditions. They are also capable of demonstrating airway growth-related changes over a two-year period.We conclude that the IOS parameters AX and the eRIC model derived parameter Cp are the most reliable parameters to track lung function in children before and after bronchodilator and over a time period (2 years).Which model is more suitable for interpreting IOS data?IOS data are equally well-modelled by eRIC and aRIC models, based on the close correlations of their corresponding parameters - excluding upper airway shunt compliance. The eRIC model is a more parsimonious and equally powerful model in capturing the differences in IOS indices between SAI and H children. Therefore, it may be considered a clinically-preferred model of lung function.

     

Birefringence Changes of Dendrites in Mouse Hippocampal Slices Revealed with Polarizing Microscopy

Intrinsic optical signal (IOS) imaging has been widely used to map the patterns of brain activity in vivo in a label-free manner. Traditional IOS refers to changes in light transmission, absorption, reflectance, and scattering of the brain tissue. Here, we use polarized light for IOS imaging to monitor structural changes of cellular and subcellular architectures due to their neuronal activity in isolated brain slices. To reveal fast spatiotemporal changes of subcellular structures associated with neuronal activity, we developed the instantaneous polarized light microscope (PolScope), which allows us to observe birefringence changes in neuronal cells and tissues while stimulating neuronal activity. The instantaneous PolScope records changes in transmission, birefringence, and slow axis orientation in tissue at a high spatial and temporal resolution using a single camera exposure. These capabilities enabled us to correlate polarization-sensitive IOS with traditional IOS on the same preparations. We detected reproducible spatiotemporal changes in both IOSs at the stratum radiatum in mouse hippocampal slices evoked by electrical stimulation at Schaffer collaterals. Upon stimulation, changes in traditional IOS signals were broadly uniform across the area, whereas birefringence imaging revealed local variations not seen in traditional IOS. Locations with high resting birefringence produced larger stimulation-evoked birefringence changes than those produced at low resting birefringence. Local application of glutamate to the synaptic region in CA1 induced an increase in both transmittance and birefringence signals. Blocking synaptic transmission with inhibitors CNQX (for AMPA-type glutamate receptor) and D-APV (for NMDA-type glutamate receptor) reduced the peak amplitude of the optical signals. Changes in both IOSs were enhanced by an inhibitor of the membranous glutamate transporter, DL-TBOA. Our results indicate that the detection of activity-induced structural changes of the subcellular architecture in dendrites is possible in a label-free manner.     

Association of FcγRIIa R131H polymorphism with idiopathic pulmonary fibrosis severity and progression

Background

Health status, dyspnea and psychological status are important clinical outcomes in chronic obstructive pulmonary disease (COPD). However, forced expiratory volume in one second (FEV₁) measured by spirometry, the standard measurement of airflow limitation, has only a weak relationship with these outcomes in COPD. Recently, in addition to spirometry, impulse oscillometry (IOS) measuring lung resistance (R) and reactance (X) is increasingly being used to assess pulmonary functional impairment.

Methods

We aimed to identify relationships between IOS measurements and patient-reported outcomes in 65 outpatients with stable COPD. We performed pulmonary function testing, IOS, high-resolution computed tomography (CT), and assessment of health status using the St. George's Respiratory Questionnaire (SGRQ), dyspnea using the Medical Research Council (MRC) scale and psychological status using the Hospital Anxiety and Depression Scale (HADS). We then investigated the relationships between these parameters. For the IOS measurements, we used lung resistance at 5 and 20 Hz (R5 and R20, respectively) and reactance at 5 Hz (X5). Because R5 and R20 are regarded as reflecting total and proximal airway resistance, respectively, the fall in resistance from R5 to R20 (R5-R20) was used as a surrogate for the resistance of peripheral airways. X5 was also considered to represent peripheral airway abnormalities.

Results

R5-R20 and X5 were significantly correlated with the SGRQ and the MRC. These correlation coefficients were greater than when using other objective measurements of pulmonary function, R20 on the IOS and CT instead of R5-R20 and X5. Multiple regression analyses showed that R5-R20 or X5 most significantly accounted for the SGRQ and MRC scores.

Conclusions

IOS measurements, especially indices of peripheral airway function, are significantly correlated with health status and dyspnea in patients with COPD. Therefore, in addition to its simplicity and non-invasiveness, IOS may be a useful clinical tool not only for detecting pulmonary functional impairment, but also to some extent at least estimating the patient's quality of daily life and well-being.     

IL-10 Gene Polymorphisms Are Associated with Post-Bronchiolitis Lung Function Abnormalities at Six Years of Age

Aim

Interleukin-10 (IL-10) has been associated with wheezing and asthma in children and the genetic variation of the IL-10 cytokine production may be linked to post-bronchiolitis lung function. We used impulse oscillometry (IOS) to evaluate the associations of IL10 polymorphisms with lung function at a median age of 6.3 years in children hospitalised for bronchiolitis before six months of age.

Methods

We performed baseline and post-exercise IOS on 103 former bronchiolitis patients. Data on single nucleotide polymorphisms (SNP) of IL10 rs1800896 (–1082G/A), rs1800871 (–819C/T), rs1800872 (–592C/A) were available for 99 children and of IL10 rs1800890 (–3575T/A) for 98 children.

Results

IL10 rs1800896, rs1800871 and rs1800872 combined genotype AA+CT+CA and carriage of haplotype ATA, respectively, were associated with higher resistance and lower reactance in baseline IOS in adjusted analyses. At IL10 rs1800890, the A/A-genotype and carriers of A-allele were associated with lower reactance in baseline IOS. There were no significant associations between the studied SNPs and airway hyper-reactivity to exercise.

Conclusion

Low-IL-10-producing polymorphisms in the IL-10 encoding gene were associated with obstructive lung function parameters, suggesting an important role for IL-10 in development of lung function deficit in early bronchiolitis patients.     

Non-Visual Effects of Light on Melatonin,Alertness and Cognitive Performance: Can Blue-Enriched Light Keep Us Alert?

Background

Light exposure can cascade numerous effects on the human circadian process via the non-imaging forming system, whose spectral relevance is highest in the short-wavelength range. Here we investigated if commercially available compact fluorescent lamps with different colour temperatures can impact on alertness and cognitive performance.

Methods

Sixteen healthy young men were studied in a balanced cross-over design with light exposure of 3 different light settings (compact fluorescent lamps with light of 40 lux at 6500K and at 2500K and incandescent lamps of 40 lux at 3000K) during 2 h in the evening.

Results

Exposure to light at 6500K induced greater melatonin suppression, together with enhanced subjective alertness, well-being and visual comfort. With respect to cognitive performance, light at 6500K led to significantly faster reaction times in tasks associated with sustained attention (Psychomotor Vigilance and GO/NOGO Task), but not in tasks associated with executive function (Paced Visual Serial Addition Task). This cognitive improvement was strongly related with attenuated salivary melatonin levels, particularly for the light condition at 6500K.

Conclusions

Our findings suggest that the sensitivity of the human alerting and cognitive response to polychromatic light at levels as low as 40 lux, is blue-shifted relative to the three-cone visual photopic system. Thus, the selection of commercially available compact fluorescent lights with different colour temperatures significantly impacts on circadian physiology and cognitive performance at home and in the workplace.     

Glutamate receptor-mediated taurine release from the hippocampus during oxidative stress

Background

Hippocampal slices swell and release taurine during oxidative stress. The influence of cellular signalling pathways on this process is unclear. Glutamate signalling can facilitate volume regulation in other CNS preparations. Therefore, we hypothesize activation of taurine release by oxidative stress results from tissue swelling and is coupled to activation of glutamate receptors.

Methods

Rat hippocampi were incubated at room temperature for 2 hr in artificial cerebrospinal fluid (aCSF) equilibrated with 95% O₂ plus 5% CO₂. For some slices, 1 mM taurine was added to the aCSF to maintain normal tissue taurine content. Slices then were perfused with aCSF at 35° C and baseline data recorded before 2 mM H₂O₂ was added. For some studies, mannitol or inhibitors of glutamate receptors or the volume-regulated anion channel (VRAC) were added before and during H₂O₂ treatment. The intensity of light transmitted through the slice (the intrinsic optical signal, IOS) was determined at 1-min intervals. Samples of perfusate were collected at 2-min intervals and amino acid contents determined by HPLC. Data were analyzed by repeated measures ANOVA and post hoc Dunnett’s test with significance indicated for p<0.05.

Results

IOS of slices prepared without taurine treatment increased significantly by 3.3±1.3% (mean±SEM) during oxidative stress. Little taurine was detected in the perfusate of these slices and the rate of taurine efflux did not change during H₂O₂ exposure. The α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate antagonist, 25 µM CNQX, but not the N-methyl-D-aspartate (NMDA) receptor antagonist, 10 µM MK-801, inhibited the increase in IOS during H₂O₂ treatment. Taurine-treated slices exposed to H₂O₂ showed no change in IOS; however, taurine efflux increased by 335±178%. When these slices were perfused with hypertonic aCSF (350 mOsm) or exposed to the VRAC inhibitor, 20 µM DCPIB, no increase in the taurine efflux rate was observed during H₂O₂ exposure. Taurine-treated slices perfused with 10 µM MK-801 during H₂O₂ exposure showed a 4.6±1.9% increase in IOS but no increase in the taurine efflux rate.

Conclusions

Taurine efflux via VRAC is critical for volume regulation of hippocampal slices exposed to oxidative stress. This increased taurine efflux does not result from direct activation of the taurine release pathway by H₂O₂. NMDA receptor activation plays an important role in taurine release during oxidative stress.

     

Mammalian <Emphasis Type="Italic">BEX</Emphasis>, <Emphasis Type="Italic">WEX</Emphasis> and <Emphasis Type="Italic">GASP</Emphasis> genes: Coding and non-coding chimaerism sustained by gene conversion events

Background  

The identification of sequence innovations in the genomes of mammals facilitates understanding of human gene function, as well as sheds light on the molecular mechanisms which underlie these changes. Although gene duplication plays a major role in genome evolution, studies regarding concerted evolution events among gene family members have been limited in scope and restricted to protein-coding regions, where high sequence similarity is easily detectable.     

In vivo optoretinography of phototransduction activation and energy metabolism in retinal photoreceptors

The objective of this study is to verify the anatomic correlate of the second (2nd) outer retina band in optical coherence tomography (OCT), and to demonstrate the potential of using intrinsic optical signal (IOS) imaging for concurrent optoretinography (ORG) of phototransduction activation and energy metabolism in stimulus activated retinal photoreceptors. A custom-designed OCT was employed for depth-resolved IOS imaging in mouse retina activated by a visible light flicker stimulation. The spatiotemporal properties of the IOS changes at the photoreceptor outer segment (OS) and inner segment (IS) were quantitatively evaluated. Rapid IOS change was observed at the OS almost right away, and the IOS at the IS was relatively slow. Comparative analysis indicates that the OS-IOS reflects transient OS deformation caused by the phototransduction activation, and IS-IOS might reflect the energy metabolism caused by mitochondria activation in retinal photoreceptors. The consistency of the distribution of the IS-IOS and the 2nd OCT band supports the IS ellipsoid (ISe), which has abundant mitochondria, as the signal source of the 2nd OCT band of the outer retina.     

Putative cross-kingdom horizontal gene transfer in sponge (Porifera) mitochondria

Background  

The mitochondrial genome of Metazoa is usually a compact molecule without introns. Exceptions to this rule have been reported only in corals and sea anemones (Cnidaria), in which group I introns have been discovered in the cox1 and nad5 genes. Here we show several lines of evidence demonstrating that introns can also be found in the mitochondria of sponges (Porifera).     

Chromato-panning: an efficient new mode of identifying suitable ligands from phage display libraries

Background  

Phage Display technology is a well established technique for high throughput screening of affinity ligands. Here we describe a new compact chromato-panning procedure for selection of suitable binders from a phage peptide display library.     

MULTI-K: accurate classification of microarray subtypes using ensemble k-means clustering

Background  

Uncovering subtypes of disease from microarray samples has important clinical implications such as survival time and sensitivity of individual patients to specific therapies. Unsupervised clustering methods have been used to classify this type of data. However, most existing methods focus on clusters with compact shapes and do not reflect the geometric complexity of the high dimensional microarray clusters, which limits their performance.     

In vivo reorganization of the actin cytoskeleton in leaves of Nicotiana tabacum L. transformed with plastin-GFP. Correlation with light-activated chloroplast responses

Background  

The actin cytoskeleton is involved in the responses of plants to environmental signals. Actin bundles play the role of tracks in chloroplast movements activated by light. Chloroplasts redistribute in response to blue light in the mesophyll cells of Nicotiana tabacum. The aim of this work was to study the relationship between chloroplast responses and the organization of actin cytoskeleton in living tobacco cells. Chloroplast movements were measured photometrically as changes in light transmission through the leaves. The actin cytoskeleton, labeled with plastin-GFP, was visualised by confocal microscopy.     

Detecting overlapping coding sequences in virus genomes

Background  

Detecting new coding sequences (CDSs) in viral genomes can be difficult for several reasons. The typically compact genomes often contain a number of overlapping coding and non-coding functional elements, which can result in unusual patterns of codon usage; conservation between related sequences can be difficult to interpret – especially within overlapping genes; and viruses often employ non-canonical translational mechanisms – e.g. frameshifting, stop codon read-through, leaky-scanning and internal ribosome entry sites – which can conceal potentially coding open reading frames (ORFs).     

Uncertainties in a carbon footprint model for detergents; quantifying the confidence in a comparative result

Background, aim, and scope  

A new trend driven by climate change concerns is the interest to label consumer products with a carbon footprint (CF) number. Here, we present a study that examines the uncertainty in the estimated CFs of a liquid and a compact powder detergent and how the uncertainty varies with the type of comparison one wishes to make.     

Recent changes in the plant composition of wetlands in the Jura Mountains

Aim

To assess vegetation changes in montane fens and wet meadows and their causes over 38 years.

Location

Wetlands, Jura Mountains (Switzerland and France).

Methods

Plots were inventoried in 1974 and re‐located in 2012 (quasi‐permanent plots) on the basis of sketches to assess changes in plant communities. The 110 plots belonged to five phytosociological alliances, two in oligotrophic fens (Caricion davallianae, Caricion fuscae) and three in wet meadows (Calthion, Molinion, Filipendulion). Changes between surveys were assessed with NMDS, and changes in species richness, Simpson diversity, species cover and frequency and the causes of these changes were evaluated by comparing ecological indicator values.

Results

Changes in species composition varied between alliances, with a general trend towards more nutrient‐rich flora with less light at ground level. Species diversity declined, with a marked decreasing trend for the typical species of each alliance. These species were partly replaced by species belonging to nitrophilous and mesophilous grasslands. However, no trend towards drier conditions was detected in these wetlands. The largest changes, with an important colonization by nitrophilous species, occurred in the Swiss sites, where grazing was banned 25 years ago. As a result of floral shifts, many plots previously belonging to fens or wet mesotrophic meadows shifted to an alliance of the wet meadows, generally Filipendulion. Moreover, communities showed a slight trend towards more thermophilous flora.

Conclusions

The investigated wetlands in the Jura Mountains have suffered mainly from eutrophication due to land‐use abandonment and N deposition, with a loss of typical species. Areas with constant land use (grazing or mowing) showed less marked changes in species composition. The most important action to conserve these wetlands is to maintain or reintroduce the traditional practices of extensive mowing and livestock grazing in the wetlands, especially in areas where they were abandoned 25 years ago. This previous land‐use change was intended to improve fen conservation, but it was obviously the wrong measure for conservation purposes.     

Analytical approximations for the amplitude and period of a relaxation oscillator

Background  

Analysis and design of complex systems benefit from mathematically tractable models, which are often derived by approximating a nonlinear system with an effective equivalent linear system. Biological oscillators with coupled positive and negative feedback loops, termed hysteresis or relaxation oscillators, are an important class of nonlinear systems and have been the subject of comprehensive computational studies. Analytical approximations have identified criteria for sustained oscillations, but have not linked the observed period and phase to compact formulas involving underlying molecular parameters.     

Effective carbon partitioning driven by exotic phloem-specific regulatory elements fused to the Arabidopsis thaliana AtSUC2 sucrose-proton symporter gene

Background  

AtSUC2 (At1g22710) from Arabidopsis thaliana encodes a phloem-localized sucrose/proton symporter required for efficient photoassimilate transport from source tissues to sink tissues. AtSUC2 plays a key role in coordinating the demands of sink tissues with the output capacity of source leaves, and in maintaining phloem hydrostatic pressure during changes in plant-water balance. Expression and activity are regulated, both positively and negatively, by developmental (sink to source transition) and environmental cues, including light, diurnal changes, photoassimilate levels, turgor pressure, drought and osmotic stress, and hormones.     

Temporo-Spectral Imaging of Intrinsic Optical Signals during Hypoxia-Induced Spreading Depression-Like Depolarization

Spreading depression (SD) is characterized by a sustained near-complete depolarization of neurons, a massive depolarization of glia, and a negative deflection of the extracellular DC potential. These electrophysiological signs are accompanied by an intrinsic optical signal (IOS) which arises from changes in light scattering and absorption. Even though the underlying mechanisms are unclear, the IOS serves as non-invasive tool to define the spatiotemporal dynamics of SD in brain slices. Usually the tissue is illuminated by white light, and light reflectance or transmittance is monitored. Using a polychromatic, fast-switchable light source we now performed temporo-spectral recordings of the IOS associated with hypoxia-induced SD-like depolarization (HSD) in rat hippocampal slices kept in an interface recording chamber. Recording full illumination spectra (320-680 nm) yielded distinct reflectance profiles for the different phases of HSD. Early during hypoxia tissue reflectance decreased within almost the entire spectrum due to cell swelling. HSD was accompanied by a reversible reflectance increase being most pronounced at 400 nm and 460 nm. At 440 nm massive porphyrin absorption (Soret band) was detected. Hypotonic solutions, Ca(2+)-withdrawal and glial poisoning intensified the reflectance increase during HSD, whereas hypertonic solutions dampened it. Replacement of Cl(-) inverted the reflectance increase. Inducing HSD by cyanide distorted the IOS and reflectance at 340-400 nm increased irreversibly. The pronounced changes at short wavelengths (380 nm, 460 nm) and their cyanide sensitivity suggest that block of mitochondrial metabolism contributes to the IOS during HSD. For stable and reliable IOS recordings during HSD wavelengths of 460-560 nm are recommended.     

High-susceptibility of photosynthesis to photoinhibition in the tropical plant Ficus microcarpa L. f. cv. Golden Leaves

Background  

The tropical plant Ficus microcarpa L. f. cv. Golden Leaves (GL) is a high-light sensitive tropical fig tree in which sun-leaves are yellow and shade-leaves are green. We compared the response of photosynthetic activities to strong light between GL and its wild-type (WT, Ficus microcarpa L. f.).     

Digital stereophotogrammetry based on circular markers and zooming cameras: evaluation of a method for 3D analysis of small motions in orthopaedic research

Background  

Orthopaedic research projects focusing on small displacements in a small measurement volume require a radiation free, three dimensional motion analysis system. A stereophotogrammetrical motion analysis system can track wireless, small, light-weight markers attached to the objects. Thereby the disturbance of the measured objects through the marker tracking can be kept at minimum. The purpose of this study was to develop and evaluate a non-position fixed compact motion analysis system configured for a small measurement volume and able to zoom while tracking small round flat markers in respect to a fiducial marker which was used for the camera pose estimation.