Loss of alveolar membrane diffusing capacity and pulmonary capillary blood volume in pulmonary arterial hypertension

Background

Reduced gas transfer in patients with pulmonary arterial hypertension (PAH) is traditionally attributed to remodeling and progressive loss of pulmonary arterial vasculature that results in decreased capillary blood volume available for gas exchange.

Methods

We tested this hypothesis by determination of lung diffusing capacity (DL) and its components, the alveolar capillary membrane diffusing capacity (D_m) and lung capillary blood volume (V_c) in 28 individuals with PAH in comparison to 41 healthy individuals, and in 19 PAH patients over time. Using single breath simultaneous measure of diffusion of carbon monoxide (DL_CO) and nitric oxide (DL_NO), DL and D_m were respectively determined, and V_c calculated. D_m and V_c were evaluated over time in relation to standard clinical indicators of disease severity, including brain natriuretic peptide (BNP), 6-minute walk distance (6MWD) and right ventricular systolic pressure (RVSP) by echocardiography.

Results

Both DL_CO and DL_NO were reduced in PAH as compared to controls and the lower DL in PAH was due to loss of both D_m and V_c (all p < 0.01). While DL_CO of PAH patients did not change over time, DL_NO decreased by 24 ml/min/mmHg/year (p = 0.01). Consequently, D_m decreased and V_c tended to increase over time, which led to deterioration of the D_m/V_c ratio, a measure of alveolar-capillary membrane functional efficiency without changes in clinical markers.

Conclusions

The findings indicate that lower than normal gas transfer in PAH is due to loss of both D_m and V_c, but that deterioration of D_m/V_c over time is related to worsening membrane diffusion.     

Characterization of Lung Function Impairment in Adults with Bronchiectasis

Background

Characteristics of lung function impairment in bronchiectasis is not fully understood.

Objectives

To determine the factors associated with lung function impairment and to compare changes in spirometry during bronchiectasis exacerbation and convalescence (1 week following 14-day antibiotic therapy).

Methods

We recruited 142 patients with steady-state bronchiectasis, of whom 44 with acute exacerbations in the follow-up were included in subgroup analyses. Baseline measurements consisted of chest high-resolution computed tomography (HRCT), sputum volume, purulence and bacteriology, spirometry and diffusing capacity. Spirometry, but not diffusing capacity, was examined during acute exacerbations and convalescence.

Results

In the final multivariate models, having bronchiectasis symptoms for 10 years or greater (OR = 4.75, 95%CI: 1.46–15.43, P = 0.01), sputum culture positive for Pseudomonas aeruginosa (OR = 4.93, 95%CI: 1.52–15.94, P<0.01) and HRCT total score being 12 or greater (OR = 7.77, 95%CI: 3.21–18.79, P<0.01) were the major variables associated with FEV₁ being 50%pred or less; and the only variable associated with reduced D_LCO was 4 or more bronchiectatic lobes (OR = 5.91, 95%CI: 2.20–17.23, P<0.01). Overall differences in FVC and FEV₁ during exacerbations and convalescence were significant (P<0.05), whereas changes in other spirometric parameters were less notable. This applied even when stratified by the magnitude of FEV₁ and D_LCO reduction at baseline.

Conclusion

Significant lung function impairment should raise alert of chest HRCT abnormality and sputum culture positive for Pseudomonas aeruginosa, in patients with predominantly mild to moderate steady-state bronchiectasis. Acute exacerbations elicited reductions in FVC and FEV₁. Changes of other spirometric parameters were less significant during exacerbations.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01761214","term_id":"NCT01761214"}}NCT01761214     

Effects of Elevated CO2 and Nitrogen Deposition on Ecosystem Carbon Fluxes on the Sanjiang Plain Wetland in Northeast China

Background

Increasing atmospheric CO₂ and nitrogen (N) deposition across the globe may affect ecosystem CO₂ exchanges and ecosystem carbon cycles. Additionally, it remains unknown how increased N deposition and N addition will alter the effects of elevated CO₂ on wetland ecosystem carbon fluxes.

Methodology/Principal Findings

Beginning in 2010, a paired, nested manipulative experimental design was used in a temperate wetland of northeastern China. The primary factor was elevated CO₂, accomplished using Open Top Chambers, and N supplied as NH₄NO₃ was the secondary factor. Gross primary productivity (GPP) was higher than ecosystem respiration (ER), leading to net carbon uptake (measured by net ecosystem CO₂ exchange, or NEE) in all four treatments over the growing season. However, their magnitude had interannual variations, which coincided with air temperature in the early growing season, with the soil temperature and with the vegetation cover. Elevated CO₂ significantly enhanced GPP and ER but overall reduced NEE because the stimulation caused by the elevated CO₂ had a greater impact on ER than on GPP. The addition of N stimulated ecosystem C fluxes in both years and ameliorated the negative impact of elevated CO₂ on NEE.

Conclusion/Significance

In this ecosystem, future elevated CO₂ may favor carbon sequestration when coupled with increasing nitrogen deposition.     

Increased Risk of Dementia in Patients Exposed to Nitrogen Dioxide and Carbon Monoxide: A Population-Based Retrospective Cohort Study

Background

The air pollution caused by vehicular emissions is associated with cognitive decline. However, the associations between the levels of nitrogen dioxide (NO₂) and carbon monoxide (CO) exposure and dementia remain poorly defined and have been addressed in only a few previous studies.

Materials and Methods

In this study, we obtained data on 29547 people from the National Health Insurance Research Database (NHIRD) of Taiwan, including data on 1720 patients diagnosed with dementia between 2000 and 2010, and we evaluated the risk of dementia among four levels of air pollutant. Detailed data on daily air pollution were available from January 1, 1998 to December 31, 2010. Yearly average concentrations of pollutants were calculated from the baseline to the date of dementia occurrence, withdrawal of patients, or the end of the study, and these data were categorized into quartiles, with Q1 being the lowest level and Q4 being the highest.

Results

In the case of NO₂, the adjusted hazard ratios (HRs) of dementia for all participants in Q2, Q3, and Q4 compared to Q1 were 1.10 (95% confidence interval (CI), 0.96–1.26), 1.01 (95% CI, 0.87–1.17), and 1.54 (95% CI, 1.34–1.77), and in the case of CO, the adjusted HRs were 1.07 (95% CI, 0.92–1.25), 1.37 (95% CI, 1.19–1.58), and 1.61 (95% CI, 1.39–1.85).

Conclusion

The results of this large retrospective, population-based study indicate that exposure to NO₂ and CO is associated with an increased risk of dementia in the Taiwanese population.     

The Health Effects of a Forest Environment on Subclinical Cardiovascular Disease and Heath-Related Quality of Life

Background

Assessment of health effects of a forest environment is an important emerging area of public health and environmental sciences.

Purpose

To demonstrate the long-term health effects of living in a forest environment on subclinical cardiovascular diseases (CVDs) and health-related quality of life (HRQOL) compared with that in an urban environment.

Materials and Methods

This study included the detailed health examination and questionnaire assessment of 107 forest staff members (FSM) and 114 urban staff members (USM) to investigate the long-term health effects of a forest environment. Air quality monitoring between the forest and urban environments was compared. In addition, work-related factors and HRQOL were evaluated.

Results

Levels of total cholesterol, low-density lipoprotein cholesterol, and fasting glucose in the USM group were significantly higher than those in the FSM group. Furthermore, a significantly higher intima-media thickness of the internal carotid artery was found in the USM group compared with that in the FSM group. Concentrations of air pollutants, such as NO, NO₂, NO_x, SO₂, CO, PM_2.5, and PM₁₀ in the forest environment were significantly lower compared with those in the outdoor urban environment. Working hours were longer in the FSM group; however, the work stress evaluation as assessed by the job content questionnaire revealed no significant differences between FSM and USM. HRQOL evaluated by the World Health Organization Quality of Life-BREF questionnaire showed FSM had better HRQOL scores in the physical health domain.

Conclusions

This study provides evidence of the potential beneficial effects of forest environments on CVDs and HRQOL.     

13[C]-Urea Breath Test as a Novel Point-of-Care Biomarker for Tuberculosis Treatment and Diagnosis

Background

Pathogen-specific metabolic pathways may be detected by breath tests based on introduction of stable isotopically-labeled substrates and detection of labeled products in exhaled breath using portable infrared spectrometers.

Methodology/Principal Findings

We tested whether mycobacterial urease activity could be utilized in such a breath test format as the basis of a novel biomarker and diagnostic for pulmonary TB. Sensitized New-Zealand White Rabbits underwent bronchoscopic infection with either Mycobacterium bovis or Mycobacterium tuberculosis. Rabbits were treated with 25 mg/kg of isoniazid (INH) approximately 2 months after infection when significant cavitary lung pathology was present. [¹³C] urea was instilled directly into the lungs of intubated rabbits at selected time points, exhaled air samples analyzed, and the kinetics of δ¹³CO₂ formation were determined. Samples obtained prior to inoculation served as control samples for background ¹³CO₂ conversion in the rabbit model. ¹³CO₂, from metabolic conversion of [¹³C]-urea by mycobacterial urease activity, was readily detectable in the exhaled breath of infected rabbits within 15 minutes of administration. Analyses showed a rapid increase in the rate of ¹³CO₂ formation both early in disease and prior to treatment with INH. Following INH treatment, all evaluable rabbits showed a decrease in the rate of ¹³CO₂ formation.

Conclusions/Significance

Urea breath testing may provide a useful diagnostic and biomarker assay for tuberculosis and for treatment response. Future work will test specificity for M. tuberculosis using lung-targeted dry powder inhalation formulations, combined with co-administering oral urease inhibitors together with a saturating oral dose of unlabeled urea, which would prevent the δ¹³CO₂ signal from urease-positive gastrointestinal organisms.     

Dopamine D2-Like Receptors Modulate Unconditioned Fear: Role of the Inferior Colliculus

Background

A reduction of dopamine release or D₂ receptor blockade in the terminal fields of the mesolimbic system clearly reduces conditioned fear. Injections of haloperidol, a preferential D₂ receptor antagonist, into the inferior colliculus (IC) enhance the processing of unconditioned aversive information. However, a clear characterization of the interplay of D₂ receptors in the mediation of unconditioned and conditioned fear is still lacking.

Methods

The present study investigated the effects of intra-IC injections of the D₂ receptor-selective antagonist sulpiride on behavior in the elevated plus maze (EPM), auditory-evoked potentials (AEPs) to loud sounds recorded from the IC, fear-potentiated startle (FPS), and conditioned freezing.

Results

Intra-IC injections of sulpiride caused clear proaversive effects in the EPM and enhanced AEPs induced by loud auditory stimuli. Intra-IC sulpiride administration did not affect FPS or conditioned freezing.

Conclusions

Dopamine D₂-like receptors of the inferior colliculus play a role in the modulation of unconditioned aversive information but not in the fear-potentiated startle response.     

Bronchial responsiveness is related to increased exhaled NO (FE(NO)) in non-smokers and decreased FE(NO) in smokers

Rationale

Both atopy and smoking are known to be associated with increased bronchial responsiveness. Fraction of nitric oxide (NO) in the exhaled air (FE_NO), a marker of airways inflammation, is decreased by smoking and increased by atopy. NO has also a physiological bronchodilating and bronchoprotective role.

Objectives

To investigate how the relation between FE_NO and bronchial responsiveness is modulated by atopy and smoking habits.

Methods

Exhaled NO measurements and methacholine challenge were performed in 468 subjects from the random sample of three European Community Respiratory Health Survey II centers: Turin (Italy), Gothenburg and Uppsala (both Sweden). Atopy status was defined by using specific IgE measurements while smoking status was questionnaire-assessed.

Main Results

Increased bronchial responsiveness was associated with increased FE_NO levels in non-smokers (p = 0.02) and decreased FE_NO levels in current smokers (p = 0.03). The negative association between bronchial responsiveness and FE_NO was seen only in the group smoking less <10 cigarettes/day (p = 0.008). Increased bronchial responsiveness was associated with increased FE_NO in atopic subjects (p = 0.04) while no significant association was found in non-atopic participants. The reported interaction between FE_NO and smoking and atopy, respectively were maintained after adjusting for possible confounders (p-values<0.05).

Conclusions

The present study highlights the interactions of the relationship between FE_NO and bronchial responsiveness with smoking and atopy, suggesting different mechanisms behind atopy- and smoking-related increases of bronchial responsiveness.     

Comparison of the Effects of Air Pollution on Outpatient and Inpatient Visits for Asthma: A Population-Based Study in Taiwan

Background

A nationwide asthma survey on the effects of air pollution is lacking in Taiwan. The purpose of this study was to evaluate the time trend and the relationship between air pollution and health care services for asthma in Taiwan.

Methods

Health care services for asthma and ambient air pollution data were obtained from the National Health Insurance Research database and Environmental Protection Administration from 2000 through 2009, respectively. Health care services, including those related to the outpatient and inpatient visits were compared according to the concentration of air pollutants.

Results

The number of asthma-patient visits to health-care facilities continue to increase in Taiwan. Relative to the respective lowest quartile of air pollutants, the adjusted relative risks (RRs) of the outpatient visits in the highest quartile were 1.10 (P-trend  = 0.013) for carbon monoxide (CO), 1.10 (P-trend  = 0.015) for nitrogen dioxide (NO₂), and 1.20 (P-trend <0.0001) for particulate matter with an aerodynamic diameter ≦10µm (PM₁₀) in the child group (aged 0–18). For adults aged 19–44, the RRs of outpatient visits were 1.13 (P-trend = 0.078) for CO, 1.17 (P-trend = 0.002) for NO_2, and 1.13 (P-trend <0.0001) for PM₁₀. For adults aged 45–64, the RRs of outpatient visits were 1.15 (P-trend = 0.003) for CO, 1.19 (P-trend = 0.0002) for NO_2, and 1.10 (P-trend = 0.001) for PM₁₀. For the elderly (aged≥ 65), the RRs of outpatient visits in were 1.12 (P-trend  = 0.003) for NO₂ and 1.10 (P-trend  = 0.006) for PM_10. For inpatient visits, the RRs across quartiles of CO level were 1.00, 1.70, 1.92, and 1.86 (P-trend  = 0.0001) in the child group. There were no significant linear associations between inpatient visits and air pollutants in other groups.

Conclusions

There were positive associations between CO levels and childhood inpatient visits as well as NO₂, CO and PM₁₀ and outpatient visits.     

Effect of exercise on hyperactivity,impulsivity and dopamine D2 receptor expression in the substantia nigra and striatum of spontaneous hypertensive rats

[Purpose]

Attention-deficit/hyperactivity disorder (ADHD) is a heritable, chronic, neurobehavioral disorder that is characterized by hyperactivity, inattention, and impulsivity. It is commonly believed that the symptoms of ADHD are closely associated with hypo-function of the dopamine system. Dopamine D₂ receptor activation decreases the excitability of dopamine neurons, as well as the release of dopamine. Physical exercise is known to improve structural and functional impairments in neuropsychiatric disorders. We investigated the therapeutic effect of exercise on ADHD.

[Methods]

Open field task and elevated-plus maze task were used in the evaluation of hyperactivity and impulsivity, respectively. Dopamine D₂ receptor expression in the substantia nigra and striatum were evaluated by western blotting.

[Results]

The present results indicated that ADHD rats showed hyperactivity and impulsivity. Dopamine D₂ receptor expression in the substantia nigra and striatum were increased in ADHD rats. Exercise alleviated hyperactivity and impulsivity in ADHD rats. Furthermore, dopamine D₂ receptor expression in ADHD rats was also decreased by exercise.

[Conclusion]

We thus showed that exercise effectively alleviates ADHD-induced symptoms through enhancing dopamine D₂ expression in the brain.     

How air pollution influences clinical management of respiratory diseases. A case-crossover study in Milan

Background

Environmental pollution is a known risk factor for multiple diseases and furthermore increases rate of hospitalisations. We investigated the correlation between emergency room admissions (ERAs) of the general population for respiratory diseases and the environmental pollutant levels in Milan, a metropolis in northern Italy.

Methods

We collected data from 45770 ERAs for respiratory diseases. A time-stratified case-crossover design was used to investigate the association between air pollution levels and ERAs for acute respiratory conditions. The effects of air pollutants were investigated at lag 0 to lag 5, lag 0–2 and lag 3–5 in both single and multi-pollutant models, adjusted for daily weather variables.

Results

An increase in ozone (O₃) levels at lag 3–5 was associated with a 78% increase in the number of ERAs for asthma, especially during the warm season. Exposure to carbon monoxide (CO) proved to be a risk factor for pneumonia at lag 0–2 and in the warm season increased the risk of ERA by 66%. A significant association was found between ERAs for COPD exacerbation and levels of sulphur dioxide (SO₂), CO, nitrate dioxide (NO₂), and particulate matter (PM₁₀ and PM_2.5). The multipollutant model that includes all pollutants showed a significant association between CO (26%) and ERA for upper respiratory tract diseases at lag 0–2. For chronic obstructive pulmonary disease (COPD) exacerbations, only CO (OR 1.19) showed a significant association.

Conclusions

Exposure to environmental pollution, even at typical low levels, can increase the risk of ERA for acute respiratory diseases and exacerbation of obstructive lung diseases in the general population.     

Pulse Wave Transit Time Measurements of Cardiac Output in Septic Shock Patients: A Comparison of the Estimated Continuous Cardiac Output System with Transthoracic Echocardiography

Background

We determined reliability of cardiac output (CO) measured by pulse wave transit time cardiac output system (esCCO system; CO_esCCO) vs transthoracic echocardiography (CO_TTE) in mechanically ventilated patients in the early phase of septic shock. A secondary objective was to assess ability of esCCO to detect change in CO after fluid infusion.

Methods

Mechanically ventilated patients admitted to the ICU, aged >18 years, in sinus rhythm, in the early phase of septic shock were prospectively included. We performed fluid infusion of 500ml of crystalloid solution over 20 minutes and recorded CO by EsCCO and TTE immediately before (T0) and 5 minutes after (T1) fluid administration. Patients were divided into 2 groups (responders and non-responders) according to a threshold of 15% increase in CO_TTE in response to volume expansion.

Results

In total, 25 patients were included, average 64±15 years, 15 (60%) were men. Average SAPSII and SOFA scores were 55±21.3 and 13±2, respectively. ICU mortality was 36%. Mean cardiac output at T0 was 5.8±1.35 L/min by esCCO and 5.27±1.17 L/min by CO_TTE. At T1, respective values were 6.63 ± 1.57 L/min for esCCO and 6.10±1.29 L/min for CO_TTE. Overall, 12 patients were classified as responders, 13 as non-responders by the reference method. A threshold of 11% increase in CO_esCCO was found to discriminate responders from non-responders with a sensitivity of 83% (95% CI, 0.52-0.98) and a specificity of 77% (95% CI, 0.46-0.95).

Conclusion

We show strong correlation esCCO and echocardiography for measuring CO, and change in CO after fluid infusion in ICU patients.     

Aerobic Fitness in Children and Young Adults with Primary Ciliary Dyskinesia

Background

Although aerobic fitness is regarded as an overall prognostic measure of morbidity and mortality, its evaluation in the chronic progressive sinopulmonary disease primary ciliary dyskinesia (PCD) has been infrequently and inconsistently reported. Here we assessed peak oxygen uptake (VO_2peak) in a large well-characterized cohort of PCD patients, and explored whether VO_2peak was associated with parameters of pulmonary function, self-reported physical limitations, and physical activity level.

Methods

VO_2peak, spirometry, diffusing capacity, whole-body plethysmography, and nitrogen multiple breath inert gas washout (N₂ MBW) were assessed in a cross-sectional, single-occasion study of clinically stable children and young adults with PCD. We used a questionnaire including self-reported physical limitations in everyday life or in vigorous activities, and estimation of weekly hours of strenuous physical activity. VO_2peak in PCD patients was compared with that in matched, healthy control subjects and a national reference.

Results

Forty-four PCD patients aged 6–29 years exhibited reduced VO_2peak compared to healthy controls (P<0.001) and the national reference. VO_2peak was abnormal (z-score <–1.96) in 34% of PCD patients. Spirometric values, RV/TLC, and indices of N₂ MBW were significantly abnormal, but VO_2peak only correlated with FEV₁ and DL_CO/V_A. VO_2peak correlated with complaints of moderate or significant limitations in vigorous activities (P = 0.0001), exhibited by 39% of PCD patients.

Conclusion

One-third of PCD patients exhibited substantially lower aerobic fitness than healthy subjects. Aerobic fitness correlated with FEV₁, DL_CO/V_A and self-reported complaints of limitations in vigorous physical activity. These findings are most likely explained by PCD pulmonary disease and its impact on pulmonary function and physical ability. Considering fitness as an important outcome and including regular strenuous physical activity in PCD treatment would probably altogether increase pulmonary clearance, lung function, aerobic fitness, and quality of life, and prevent lifestyle-related diseases.     

Differences of cardiac output measurements by open-circuit acetylene uptake in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: a cohort study

Background

As differences in gas exchange between pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) have been demonstrated, we asked if cardiac output measurements determined by acetylene (C₂H₂) uptake significantly differed in these diseases when compared to the thermodilution technique.

Method

Single-breath open-circuit C₂H₂ uptake, thermodilution, and cardiopulmonary exercise testing were performed in 72 PAH and 32 CTEPH patients.

Results

In PAH patients the results for cardiac output obtained by the two methods showed an acceptable agreement with a mean difference of -0.16 L/min (95% CI -2.64 to 2.32 L/min). In contrast, the agreement was poorer in the CTEPH group with the difference being -0.56 L/min (95% CI -4.96 to 3.84 L/min). Functional dead space ventilation (44.5 ± 1.6 vs. 32.2 ± 1.4%, p < 0.001) and the mean arterial to end-tidal CO₂ gradient (9.9 ± 0.8 vs. 4.1 ± 0.5 mmHg, p < 0.001) were significantly elevated among CTEPH patients.

Conclusion

Cardiac output evaluation by the C₂H₂ technique should be interpreted with caution in CTEPH, as ventilation to perfusion mismatching might be more relevant than in PAH.     

A Customized Bolus Produced Using a 3-Dimensional Printer for Radiotherapy

Objective

Boluses are used in high-energy radiotherapy in order to overcome the skin sparing effect. In practice though, commonly used flat boluses fail to make a perfect contact with the irregular surface of the patient’s skin, resulting in air gaps. Hence, we fabricated a customized bolus using a 3-dimensional (3D) printer and evaluated its feasibility for radiotherapy.

Methods

We designed two kinds of bolus for production on a 3D printer, one of which was the 3D printed flat bolus for the Blue water phantom and the other was a 3D printed customized bolus for the RANDO phantom. The 3D printed flat bolus was fabricated to verify its physical quality. The resulting 3D printed flat bolus was evaluated by assessing dosimetric parameters such as D_{1.5 cm}, D_{5 cm}, and D_{10 cm}. The 3D printed customized bolus was then fabricated, and its quality and clinical feasibility were evaluated by visual inspection and by assessing dosimetric parameters such as D_max, D_min, D_mean, D_90%, and V_90%.

Results

The dosimetric parameters of the resulting 3D printed flat bolus showed that it was a useful dose escalating material, equivalent to a commercially available flat bolus. Analysis of the dosimetric parameters of the 3D printed customized bolus demonstrated that it is provided good dose escalation and good contact with the irregular surface of the RANDO phantom.

Conclusions

A customized bolus produced using a 3D printer could potentially replace commercially available flat boluses.     

The association of 25-hydroxyvitamin D3 and D2 with behavioural problems in childhood

Background

Higher serum concentrations of 25-hydroxyvitamin D (25(OH)D), an indicator of vitamin D synthesis and intake, have been associated with better mental health and cognitive function. Concentrations of 1,25-dihydroxyvitamin D₃ (the active vitamin D₃ metabolite) have been associated with openness and extrovert behaviour, but 25(OH)D concentrations have not been associated with behavioural problems in humans.

Methods

We investigated the prospective association between the different forms of 25(OH)D - 25(OH)D₃ and 25(OH)D₂– and childhood behavioural problems in Avon Longitudinal Study of Parents and Children (ALSPAC). Serum 25(OH)D₃ and 25(OH)D₂ concentrations were assessed at mean age 9.9 years. Incident behavioural problems were assessed with Strengths and Difficulties Questionnaire (SDQ; emotional symptoms, conduct problems, hyperactivity-inattention problems, peer relationship problems and pro-social behaviour subscales and total difficulties score) at mean age 11.7. Sample sizes varied between 2413-2666 depending on the outcome.

Results

Higher 25(OH)D₃ concentrations were weakly associated with lower risk of prosocial problems (fully adjusted odds ratio: OR (95% confidence interval: CI) 0.85 (0.74, 0.98)). Serum 25(OH)D₃ or 25(OH)D₂ concentrations were not associated with other subscales of SDQ or total difficulties score after adjusting for concfounders and other measured analytes related to vitamin D.

Conclusions

Our findings do not support the hypothesis that 25-hydroxyvitamin D status in childhood has important influences on behavioural traits in humans.     

Fractionated breath condensate sampling: H2O2 concentrations of the alveolar fraction may be related to asthma control in children

Background

Asthma is a chronic inflammatory disease of the airways but recent studies have shown that alveoli are also subject to pathophysiological changes. This study was undertaken to compare hydrogen peroxide (H₂O₂) concentrations in different parts of the lung using a new technique of fractioned breath condensate sampling.

Methods

In 52 children (9-17 years, 32 asthmatic patients, 20 controls) measurements of exhaled nitric oxide (FE_NO), lung function, H₂O₂ in exhaled breath condensate (EBC) and the asthma control test (ACT) were performed. Exhaled breath condensate was collected in two different fractions, representing mainly either the airways or the alveoli. H₂O₂ was analysed in the airway and alveolar fractions and compared to clinical parameters.

Results

The exhaled H₂O₂ concentration was significantly higher in the airway fraction than in the alveolar fraction comparing each single pair (p = 0.003, 0.032 and 0.040 for the whole study group, the asthmatic group and the control group, respectively). Asthma control, measured by the asthma control test (ACT), correlated significantly with the H₂O₂ concentrations in the alveolar fraction (r = 0.606, p = 0.004) but not with those in the airway fraction in the group of children above 12 years. FE_NO values and lung function parameters did not correlate to the H₂O₂ concentrations of each fraction.

Conclusion

The new technique of fractionated H₂O₂ measurement may differentiate H₂O₂ concentrations in different parts of the lung in asthmatic and control children. H₂O₂ concentrations of the alveolar fraction may be related to the asthma control test in children.     

The Expansion of the Pulmonary Rib Cage during Breath Stacking Is Influenced by Age in Obese Women

Objective

To analyze in obese women the acute effects of the breath stacking technique on thoraco-abdominal expansion.

Design and Methods

Nineteen obese women (BMI≥30 kg/m²) were evaluated by anthropometry, spirometry and maximal respiratory muscle pressures and successively analyzed by Opto-Electronic Plethysmography and a Wright respirometer during quiet breathing and breath stacking maneuvers and compared with a group of 15 normal-weighted healthy women. The acute effects of the maneuvers were assessed in terms of total and compartmental chest wall volumes at baseline, end of the breath stacking maneuver and after the maneuver. Obese subjects were successively classified into two groups, accordingly to the response during the maneuver, group 1 = prevalent rib cage or group 2 = abdominal expansion.

Results

Age was significantly lower in group 1 than group 2. When considering the two obese groups, FEV₁ was lower and minute ventilation was higher only in group 2 compared to controls group. During breath stacking, inspiratory capacity was significant differences in obese subjects with a smaller expansion of the pulmonary rib cage and a greater expansion of the abdomen compared to controls and also between groups 1 and 2. A significant inverse linear relationship was found between age and inspiratory capacity of the pulmonary rib cage but not of the abdomen.

Conclusions

In obese women the maximal expansion of the rib cage and abdomen is influenced by age and breath stacking maneuver could be a possible therapy for preventing respiratory complications.     

Improving ecophysiological simulation models to predict the impact of elevated atmospheric CO2 concentration on crop productivity

Background

Process-based ecophysiological crop models are pivotal in assessing responses of crop productivity and designing strategies of adaptation to climate change. Most existing crop models generally over-estimate the effect of elevated atmospheric [CO₂], despite decades of experimental research on crop growth response to [CO₂].

Analysis

A review of the literature indicates that the quantitative relationships for a number of traits, once expressed as a function of internal plant nitrogen status, are altered little by the elevated [CO₂]. A model incorporating these nitrogen-based functional relationships and mechanisms simulated photosynthetic acclimation to elevated [CO₂], thereby reducing the chance of over-estimating crop response to [CO₂]. Robust crop models to have small parameterization requirements and yet generate phenotypic plasticity under changing environmental conditions need to capture the carbon–nitrogen interactions during crop growth.

Conclusions

The performance of the improved models depends little on the type of the experimental facilities used to obtain data for parameterization, and allows accurate projections of the impact of elevated [CO₂] and other climatic variables on crop productivity.     

Effect of Atomoxetine on Hyperactivity in an Animal Model of Attention-Deficit/Hyperactivity Disorder (ADHD)

Background

Hyperactivity related behaviors as well as inattention and impulsivity are regarded as the nuclear symptoms of attention-deficit/hyperactivity disorder (ADHD).

Purpose

To investigate the therapeutic effects of atomoxetine on the motor activity in relation to the expression of the dopamine (DA) D2 receptor based on the hypothesis that DA system hypofunction causes ADHD symptoms, which would correlate with extensive D2 receptor overproduction and a lack of DA synthesis in specific brain regions: prefrontal cortex (PFC), striatum, and hypothalamus.

Methods

Young male spontaneously hypertensive rats (SHR), animal models of ADHD, were randomly divided into four groups according to the daily dosage of atomoxetine and treated for 21 consecutive days. The animals were assessed using an open-field test, and the DA D2 receptor expression was examined.

Results

The motor activity improved continuously in the group treated with atomoxetine at a dose of 1 mg/Kg/day than in the groups treated with atomoxetine at a dose of 0.25 mg/Kg/day or 0.5 mg/Kg/day. With respect to DA D₂ receptor immunohistochemistry, we observed significantly increased DA D₂ receptor expression in the PFC, striatum, and hypothalamus of the SHRs as compared to the WKY rats. Treatment with atomoxetine significantly decreased DA D₂ expression in the PFC, striatum, and hypothalamus of the SHRs, in a dose-dependent manner.

Conclusion

Hyperactivity in young SHRs can be improved by treatment with atomoxetine via the DA D2 pathway.