Mini review shows that structured light plethysmography provides a non-contact method for evaluating breathing patterns in children.

AIM: Structured light plethysmography (SLP) is a novel light-based method that captures chest wall movements to evaluate tidal breathing. We carried out a narrative mini review of the clinical use of SLP in paediatrics. METHODS: PubMed and Google Scholar were searched for papers published in English up to December 2018. This identified a methodology paper published in 2010 and eight full papers, including three paediatric studies and one paediatric case report. We also included data from ten conference abstracts and one clinical case study. RESULTS: We found data that validated the ability of SLP to differentiate airway obstruction from tidal breathing parameters and bronchodilator responsiveness for children aged two years and over. Non-contact measurement of regional chest wall movement was a unique feature. Feasibility data were scarce and more studies are needed, especially in infants. Preliminary studies suggest that SLP has the potential to be used in cases of dysfunctional breathing and neuromuscular diseases and as a follow-up tool after lung infections or surgery. CONCLUSION: Structured light plethysmography has been validated to demonstrate lung function abnormality in paediatric asthma, but further studies are needed to demonstrate its benefits over current practice and how it can be used for other conditions.

Functional effects of an interpenetrating polymer network on articular cartilage mechanical properties.

OBJECTIVE: Depletion of glycosaminoglycans (GAGs) and degradation of collagen network are early hallmarks of osteoarthritis (OA). Currently, there are no chondroprotective therapies that mitigate the loss of GAGs or effectively restore the collagen network. Recently, a novel polymeric cartilage supplement was described that forms a charged interpenetrating polymer network (IPN) reconstituting the hydrophilic properties of the extracellular matrix (ECM). To investigate the mechanism by which this hydrophilic IPN improves articular cartilage material properties, a finite element (FE) model is used to evaluate the IPN's effect on the fibrillar collagen network, nonfibrillar matrix, and interstitial fluid flow. METHODS: Bovine osteochondral plugs were degraded with chondroitinase ABC to selectively decrease GAG content. Samples were mechanically tested before and after IPN treatment using unconfined testing geometry and stress-relaxation protocol. Every measurement was modeled separately using a fibril-reinforced poroviscoelastic FE model. Measurement replication was achieved by optimizing the following model parameters: initial and strain-dependent fibril network modulus (Ef0, Efε, respectively), nonfibrillar matrix modulus (Enf), initial permeability (k0) and strain-dependent permeability factor (M). RESULTS: Based on the FE model results, treatment of native and GAG depleted cartilage with the hydrophilic IPN increases the ECM stiffness and impedes fluid flow. The IPN did not alter the stiffness of fibrillary network. Cartilage permeability and the strain-dependent permeability factor decreased with increasing IPN w/v%. CONCLUSIONS: The IPN reconstitutes cartilage material properties primarily by augmenting the hydrophilic ECM. This reinforcement of the solid phase also affects the fluid phase reestablishing low permeability.

Reinforcement of articular cartilage with a tissue-interpenetrating polymer network reduces friction and modulates interstitial fluid load support.

OBJECTIVE: Osteoarthritis (OA) is associated with increased articular cartilage hydraulic permeability and decreased maintenance of high interstitial fluid load support (IFLS) during articulation, resulting in increased friction on the cartilage solid matrix. This study assesses frictional response following in situ synthesis of an interpenetrating polymer network (IPN) designed to mimic glycosaminoglycans (GAGs) depleted during OA. METHODS: Cylindrical osteochondral explants containing various interpenetrating polymer concentrations were subjected to a torsional friction test under unconfined creep compression. Time-varying coefficient of friction, compressive engineering strain, and normalized strain values (ε/εeq) were calculated and analyzed. RESULTS: The polymer network reduced friction coefficient over the duration of the friction test, with statistically significantly reduced friction coefficients (95% confidence interval 14-34% reduced) at equilibrium compressive strain upon completion of the test (P = 0.015). A positive trend was observed relating polymer network concentration with magnitude of friction reduction compared to non-treated tissue. CONCLUSION: The cartilage-interpenetrating polymer treatment improves lubrication by augmenting the biphasic tissue's interstitial fluid phase, and additionally improves the friction dissipation of the tissue's solid matrix. This technique demonstrates potential as a therapy to augment tribological function of articular cartilage.

Accuracy and economic evaluation of screening tests for undiagnosed COPD among hypertensive individuals in Brazil.

In Brazil, prevalence of diagnosed COPD among adults aged 40 years and over is 16% although over 70% of cases remain undiagnosed. Hypertension is common and well-recorded in primary care, and frequently co-exists with COPD because of common causes such as tobacco smoking, therefore we conducted a cross-sectional screening test accuracy study in nine Basic Health Units in Brazil, among hypertensive patients aged ≥40 years to identify the optimum screening test/combinations to detect undiagnosed COPD. We compared six index tests (four screening questionnaires, microspirometer and peak flow) against the reference test defined as those below the lower limit of normal (LLN-GLI) on quality diagnostic spirometry, with confirmed COPD at clinical review. Of 1162 participants, 6.8% (n = 79) had clinically confirmed COPD. Peak flow had a higher specificity but lower sensitivity than microspirometry (sensitivity 44.3% [95% CI 33.1, 55.9], specificity 95.5% [95% CI 94.1, 96.6]). SBQ performed well compared to the other questionnaires (sensitivity 75.9% [95% CI 65.0, 84.9], specificity 59.2% [95% CI 56.2, 62.1]). A strategy requiring both SBQ and peak flow to be positive yielded sensitivity of 39.2% (95% CI 28.4, 50.9) and specificity of 97.0% (95% CI 95.7, 97.9). The use of simple screening tests was feasible within the Brazilian primary care setting. The combination of SBQ and peak flow appeared most efficient, when considering performance of the test, cost and ease of use (costing £1690 (5554 R$) with 26.7 cases detected per 1,000 patients). However, the choice of screening tests depends on the clinical setting and availability of resources.ISRCTN registration number: 11377960.

Fibre architecture and song activation rates of syringeal muscles are not lateralized in the European starling.

The songbird vocal organ, the syrinx, is composed of two sound generators, which are independently controlled by sets of two extrinsic and four intrinsic muscles. These muscles rank among the fastest vertebrate muscles, but the molecular and morphological foundations of this rapid physiological performance are unknown. Here we show that the four intrinsic muscles in the syrinx of male European starlings (Sturnus vulgaris) are composed of fast oxidative and superfast fibres. Dorsal and ventral tracheobronchialis muscles contain slightly more superfast fibres relative to the number of fast oxidative fibres than dorsal and ventral syringealis muscles. This morphological difference is not reflected in the highest, burst-like activation rate of the two muscle groups during song as assessed with electromyographic recordings. No difference in fibre type ratio was found between the corresponding muscles of the left and right sound generators. Airflow and electromyographic measurements during song indicate that maximal activation rate and speed of airflow regulation do not differ between the two sound sources. Whereas the potential for high-speed muscular control exists on both sides, the two sound generators are used differentially for modulation of acoustic parameters. These results show that large numbers of superfast fibre types are present in intrinsic syringeal muscles of a songbird, providing further confirmation of rapid contraction kinetics. However, syringeal muscles are composed of two fibre types which raises questions about the neuromuscular control of this heterogeneous muscle architecture.

Intraventricular murine Aß infusion elicits hippocampal inflammation and disrupts the consolidation, but not retrieval, of conditioned fear in C57BL6/J mice.

Although one of the defining characteristics of Alzheimer's disease is the presence of amyloid-beta (Aß) plaques, the early accumulation of soluble Aß oligomers (AßOs) may disrupt synaptic function and trigger cognitive impairments long before the appearance of plaques. Furthermore, murine models aimed at understanding how AßOs alter formation and retrieval of associative memories are conducted using human Aß species, which are more neurotoxic in the mouse brain than the native murine species. Unfortunately, there is currently a lack of attention in the literature as to what the murine version of the peptide (mAß) does to synaptic function and how it impacts the consolidation and retrieval of associative memories. In the current study, adult mice were infused with mAß 0, 2, 6, or 46 h after contextual-fear conditioning, and were tested 2-48 h later. Interestingly, only mAß infusions within 2 h of training reduced freezing behavior at test, indicating that mAß disrupted the consolidation, but not retrieval of fear memory. This consolidation deficit coincided with increased IL-1ß and reduced synaptophysin mRNA levels, without disrupting other synaptic signaling-related genes here examined. Despite differences between murine and human Aß, the deleterious functional outcomes of early-stage synaptic oligomer presence are similar. Thus, models utilizing or inducing the production of mAß in non-transgenic animals are useful in exploring the role of dysregulated synaptic plasticity and resultant learning deficits induced by Aß oligomers.

Temporary inactivation of the retrosplenial cortex causes a transient reorganization of spatial coding in the hippocampus.

The ability to navigate accurately is dependent on the integration of visual and movement-related cues. Navigation based on metrics derived from movement is referred to as path integration. Recent theories of navigation have suggested that posterior cortical areas, the retrosplenial and posterior parietal cortex, are involved in path integration during navigation. In support of this hypothesis, we have found previously that temporary inactivation of retrosplenial cortex results in dark-selective impairments on the radial maze (Cooper and Mizumori, 1999). To understand further the role of the retrosplenial cortex in navigation, we combined temporary inactivation of retrosplenial cortex with recording of complex spike cells in the hippocampus. Thus, behavioral performance during spatial memory testing could be compared with place-field responses before, and during, inactivation of retrosplenial cortex. In the first experiment, behavioral results confirmed that inactivation of retrosplenial cortex only impairs radial maze performance in darkness when animals are at asymptote levels of performance. A second experiment revealed that retrosplenial cortex inactivation impaired spatial learning during initial light training. In both experiments, the normal location of hippocampal "place fields" was changed by temporary inactivation of retrosplenial cortex, whereas other electrophysiological properties of the cells were not affected. The changes in place coding occurred in the presence, and absence, of behavioral impairments. We suggest that the retrosplenial cortex provides mnemonic spatial information for updating location codes in the hippocampus, thereby facilitating accurate path integration. In this way, the retrosplenial cortex and hippocampus may be part of an interactive neural system that mediates navigation.

A neural systems analysis of adaptive navigation.

In the field of the neurobiology of learning, significant emphasis has been placed on understanding neural plasticity within a single structure (or synapse type) as it relates to a particular type of learning mediated by a particular brain area. To appreciate fully the breadth of the plasticity responsible for complex learning phenomena, it is imperative that we also examine the neural mechanisms of the behavioral instantiation of learned information, how motivational systems interact, and how past memories affect the learning process. To address this issue, we describe a model of complex learning (rodent adaptive navigation) that could be used to study dynamically interactive neural systems. Adaptive navigation depends on the efficient integration of external and internal sensory information with motivational systems to arrive at the most effective cognitive and/or behavioral strategies. We present evidence consistent with the view that during navigation: 1) the limbic thalamus and limbic cortex is primarily responsible for the integration of current and expected sensory information, 2) the hippocampal-septal-hypothalamic system provides a mechanism whereby motivational perspectives bias sensory processing, and 3) the amygdala-prefrontal-striatal circuit allows animals to evaluate the expected reinforcement consequences of context-dependent behavioral responses. Although much remains to be determined regarding the nature of the interactions among neural systems, new insights have emerged regarding the mechanisms that underlie flexible and adaptive behavioral responses.

Hormonal and metabolic profiles in subjects with obstructive sleep apnea syndrome and the acute effects of nasal continuous positive airway pressure (CPAP) treatment.

Nocturnal secretion of growth hormone is impaired in patients with obstructive sleep apnea (OSA), but the metabolic consequences have not been reported. We measured blood levels of the hormones insulin, C-peptide, growth hormone, cortisol and glucagon together with the intermediary metabolites of carbohydrate (glucose, pyruvate, lactate, alanine) and lipid metabolism [glycerol, nonesterified fatty acids (NEFA), 3-hydroxybutyrate] in six obese nondiabetic men with OSA on two nights. In the first study, the untreated subjects showed frequent apneas and consequent hypoxemia. The hormone and metabolite concentrations were compared with those obtained on the following night when the subjects were treated effectively with nasal continuous positive airway pressure (CPAP). There were no significant differences in the concentrations of insulin, C-peptide, cortisol or glucagon. We confirmed a marked reduction in growth hormone concentrations in OSA, with a significant increase on the CPAP night. The nocturnal profiles of glucose, pyruvate, lactate, alanine and glycerol showed no differences between the two nights, but concentrations of NEFA and 3-hydroxybutyrate, both products of lipolysis, were significantly greater on the treatment night. Because growth hormone has a lipolytic action, the results suggest that suppression of secretion of growth hormone in untreated OSA results in impaired lipolysis, which is rapidly reversed by nasal CPAP.

Finding your way in the dark: the retrosplenial cortex contributes to spatial memory and navigation without visual cues.

Path integration is presumed to rely on self-motion cues to identify locations in space and is subject to cumulative error. The authors tested the hypothesis that rats use memory to reduce such errors and that the retrosplenial cortex contributes to this process. Rats were trained for 1 week to hoard food in an arena after beginning a trial from a fixed starting location; probe trials were then conducted in which they began a trial from a novel place in light or darkness. After control injections, rats searched around the training location, showing normal spatial memory. Inactivation of the retrosplenial cortex disrupted this search preference. To assess accuracy during navigation, rats were then trained to perform multiple trials daily, with a fixed or a different starting location in light or darkness. Retrosplenial cortex inactivation impaired accuracy in darkness. The retrosplenial cortex may provide mnemonic information, which decreases errors when navigating in the dark.

Evaluation of phenylalanine and tyrosine metabolism in late human pregnancy.

The [2H5]-phenylalanine method for measurement of protein metabolism requires the phenylalanine hydroxylation to tyrosine to be calculated from the tyrosine flux. Although this can be estimated, for pregnancy, we made a direct measurement of the molar ratio of the fluxes of tyrosine and phenylalanine from protein breakdown (Pt/Pp) using [2H2]-tyrosine infusion. Six normal pregnant women were studied at 37 weeks' gestation. While fasting, they were administered a 3-hour primed-constant infusion with [13C]-leucine, [2H5]-phenylalanine, and [2H2]-tyrosine. Leucine (alpha-ketoisocaproic acid [KIC]) flux was 136.2+/-15.1 micromol/kg/h (mean +/- SD), phenylalanine flux 41.2+/-5.6, and tyrosine flux 25.0+/-6.0, and phenylalanine hydroxylation was 3.3+/-2.1 micromol/kg/h. The mean tyrosine to phenylalanine molar flux ratio (Pt/Pp) was 0.52+/-0.10, lower than the ratio of 0.65 to 0.85 reported in normal nonpregnant subjects and 0.73 estimated from animal studies. We studied protein metabolism in six additional pregnant women and six nonpregnant women using [13C]-leucine and [2H5]-phenylalanine infusions only and applied the lower Pt/Pp ratio to the former group. Tyrosine flux (42.0+/-7.2 micromol/kg/h) and phenylalanine hydroxylation (9.2+/-4.2 micromol/kg/h) were significantly higher in nonpregnant subjects than in both groups of pregnant subjects. The percent contribution of phenylalanine hydroxylation to total tyrosine flux was reduced from 20% to 14%. When using [2H5]-phenylalanine to study whole-body protein metabolism in pregnancy and tyrosine flux is not measured directly by infusion of [2H2]-tyrosine, the lower Pt/Pp ratio is required. The phenylalanine model shows that tyrosine flux derived from protein breakdown and phenylalanine hydroxylation are both reduced in pregnancy.

The impact of metformin therapy on hepatic glucose production and skeletal muscle glycogen synthase activity in overweight type II diabetic patients.

The effect of metformin therapy on glucose metabolism was examined in eight overweight newly presenting untreated type II diabetic patients (five males, three females). Patients were treated for 12 weeks with either metformin (850 mg x 3) or matching placebo using a double-blind crossover study design; patients were studied at presentation and at the end of each treatment period. Insulin action was assessed by measuring activation of skeletal muscle glycogen synthase (GS) before and during a 4-hour hyperinsulinemic euglycemic clamp (100 mU.kg-1 x h-1). Metformin therapy was associated with a significant decrease in fasting blood glucose (6.8 +/- 0.6 v 8.3 +/- 0.9 mmol.L-1, P < .01) and glycosylated hemoglobin ([HbA1] 7.7% +/- 0.4% v 8.5% +/- 0.5%, P < .01) levels. Fasting hepatic glucose production (HGP) was also significantly decreased following metformin therapy (1.98 +/- 0.13 v 2.41 +/- 0.20 mg.kg-1 x min-1, P < .02), whereas fasting insulin and C-peptide concentrations remained unaltered. The decrease in basal HGP correlated closely with the decrease in fasting blood glucose concentration (r = .92, P < .001). Insulin-stimulated glucose uptake was assessed using the hyperinsulinemic euglycemic clamp technique and was increased post-metformin (3.8 +/- 0.6 v 3.1 +/- 0.7 mg.kg-1 x min-1, P < .05). This was primarily the result of increased nonoxidative glucose metabolism (1.1 +/- 0.6 v 0.4 +/- 0.6 mg.kg-1 x min-1, P < .05); oxidative glucose metabolism did not change. Metformin had no measurable effect on insulin activation of skeletal muscle GS, the rate-limiting enzyme controlling muscle glucose storage.(ABSTRACT TRUNCATED AT 250 WORDS)

Retrosplenial cortex inactivation selectively impairs navigation in darkness.

There is an emerging consensus that retrosplenial and posterior parietal cortex importantly contribute to navigation. Several theories of navigation have argued that these cortical areas, particularly retrosplenial cortex, are involved in path integration. In an effort to characterize the role of retrosplenial cortex in active navigation, the effects of temporary inactivation of retrosplenial cortex on spatial memory performance were evaluated in light and dark testing conditions. Inactivation of retrosplenial cortex selectively resulted in behavioral impairments when animals were tested in darkness. These data support the hypothesis that retrosplenial cortex contributes to navigation in darkness, perhaps by providing mnemonic associations of the visual and nonvisual environment that can be used to correct for cumulative errors that occur during path integration.

Lung function in patients with diabetes mellitus.

Lung function was assessed in 35 nonsmoking adults with insulin dependent diabetes mellitus and 34 matched control subjects. The tests included spirometry, lung volumes, CO transfer factor and maximum respiratory pressures. Additionally, in subjects under 35 years of age (20 patients and 18 controls) measurements of CO transfer factor were obtained during exercise at three different workloads. Random blood glucose and glycosylated haemoglobin were measured and each patient's diabetic history was recorded. The total lung capacity (TLC) in the patients was lower than those recorded for the controls (P less than 0.05) but there were no significant differences in respiratory muscle strength between the groups. In the young group of patients (less than 35 years) the transfer factor for CO (TLCO) was similar but the volume corrected transfer coefficient (KCO) was higher at rest than in the controls (P less than 0.02). The KCO remained high in these patients during exercise. The older patients (greater than 35 years) showed a lower TLCO (P less than 0.01) with a similar KCO to the controls. The association of a reduction in TLC and higher KCO in the young patients suggests an extrapulmonary mechanism of lung volume restriction. This is not attributable to muscle weakness but might be due to limited expansion of the rib cage. In older patients any tendency for KCO to rise may be masked by disease-related changes in the pulmonary microvasculature.

The effect of controlled-release salbutamol on sleep and nocturnal oxygenation in patients with asthma and chronic obstructive pulmonary disease.

Patients with asthma or chronic obstructive pulmonary disease (COPD) may have falls in oxygen saturation at night. We have investigated the effect of a long acting beta agonist (salbutamol CR) on nocturnal oxygen saturation (SaO2) in asthma and COPD. Eleven asthmatic and 14 COPD patients in stable condition were randomly allocated to 8 mg salbutamol CR or placebo twice daily in a double-blind, cross-over study. FEV1 at entry was 71.5% predicted in the asthmatic patients and 36% predicted in the COPD group. Each treatment period lasted 7 days, at the end of which measurements of ventilatory function and detailed sleep studies were performed. There was a significant improvement in morning FEV1 in the asthmatic patients when on active treatment and a small, but non-significant improvement in the COPD group. Sleep architecture and oxygenation were similar on placebo and on active treatment in both groups. We conclude that salbutamol CR has no significant effect on nocturnal oxygenation or sleep pattern in patients with mild asthma or moderately severe COPD.

Resting energy expenditure, substrate use, and video tapes.

OBJECTIVE: To investigate the effect of watching different types of video on energy expenditure. DESIGN: Randomised study assessing a "pleasant," an "amusing," an "exciting," and no video film clips. SUBJECTS: 12 volunteers who did not know the purpose of the study. MAIN OUTCOME MEASURES: Changes in energy expenditure, substrate use, heart rate, and aural temperature during each film clip. RESULTS: Energy expenditure was raised slightly (0.21 kJ/day) during the "exciting" film. Individual responses varied greatly. CONCLUSION: Watching different types of video seems to have little effect on resting metabolic rate.

Is it necessary to use a noseclip in the performance of spirometry using a wedge bellows device?

There is no current consensus among published guidelines on whether noseclips are required during spirometry testing. This study investigated the effect of noseclips on spirometric measurements in patients with a range of disease. Fifty-two patients (30 male; mean age 58.0 years, range 19-78; mean FEV1 82.6% predicted, range 23.8-128.3%) performed measurements of VC, FVC and FEV1 according to ARTP/BTS guidelines (1994) using a wedge bellows spirometer (Vitalograph Model S, Bucks, U.K.). All patients performed two sets of measurements (with and without noseclips) in random order (Group 1 = noseclips first; n=30; Group 2 (without noseclips first, n=22). Tests were conducted by qualified physiologists. Measurements obtained with and without the use of noseclips were similar (mean differences FEV1 -0.030 L SD 0.210 and -0.005 L SD 0.093 for Groups 1 and 2 respectively; FVC -0.007 L SD 0.109 and -0.040 L SD 0.117; VC 0.036L SD 0.137 and -0.040 L SD 0.150) and were not dependent on patient group or previous test experience. Four patients had differences outside the 95% confidence limits for each parameter. There were no significant correlations between the differences with and without noseclips and severity of lung disease, age, smoking history, BMI or lung volume (all P > 0.100). The within patient coefficient of variation did not depend on the testing method. Use of noseclips during spirometry does not systematically affect the results obtained or the within-subject repeatability. Marked individual differences highlight the importance of maintaining consistency in the method adopted for a particular patient.