Airway Tapering in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Luminal narrowing is a hallmark feature of airway remodeling in COPD, but current measures focus on airway wall remodeling. Quantification of the natural increase in cumulative cross-sectional area along the length of the human airway tree can facilitate assessment of airway narrowing. METHODS: We analysed the airway trees of 7641 subjects enrolled in the multicenter COPDGene cohort. Airway luminal tapering was assessed by estimating the slope of the change in cumulative cross-sectional area along the length of the airway tree over successive generations (T-Slope). We performed multivariable regression analyses to test the associations between T-Slope and lung function, St. George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) dyspnea score, 6-minute walk distance (6 MWD), FEV1 change, exacerbations, and all-cause mortality after adjusting for demographics, %CT emphysema, and total airway count. RESULTS: The T-Slope decreased with increasing COPD severity: 2.69 (0.70) in nonsmokers and 2.33 (0.70), 2.11 (0.65), 1.78 (0.58), 1.60 (0.53), and 1.57 (0.52) in GOLD stages 0 through 4 respectively (Jonckheere-Terpstra p=0.04). On multivariable analyses, the T-Slope was independently associated with FEV1 (ß=0.13 L, 95% CI 0.10 to 0.15, p<0.001), 6MWD (ß=15.0 m, 95%CI 10.8 to 19.2, p<0.001), change in FEV1 (ß=-4.50 ml·year-1, 95% CI -7.32 to -1.67; p=0.001), exacerbations (IRR=0.78, 95% CI 0.73 to 0.83, p<0.001), and mortality (HR=0.79, 95% CI 0.72 to 0.86, p<0.001). CONCLUSION: T-Slope is a measure of airway luminal remodeling and is associated with respiratory morbidity and mortality.

Prone positioning redistributes gravitational stress in the lung in normal conditions and in simulations of oedema.

NEW FINDINGS: What is the central question of this study? How does the interaction between posture and gravity affect the stresses on the lung, particularly in highly inflated gravitationally non-dependent regions, which are potentially vulnerable to increased mechanical stress and injury? What is the main finding and its importance? Changes in stress attributable to gravity are not well characterized between postures. Using a new metric of gravitational stress, we show that regions of the lung near maximal inflation have the greatest gravitational stresses while supine, but not while prone. In simulations of increased lung weight consistent with severe pulmonary oedema, the prone lung has lower gravitational stress in vulnerable, non-dependent regions, potentially protecting them from overinflation and injury. ABSTRACT: Prone posture changes the gravitational vector, and potentially the stress induced by tissue deformation, because a larger lung volume is gravitationally dependent when supine, but non-dependent when prone. To evaluate this, 10 normal subjects (six male and four female; age, means ± SD = 27 ± 6 years; height, 171 ± 9 cm; weight, 69 ± 13 kg; forced expiratory volume in the first second/forced expiratory volume as a percentage of predicted, 93 ± 6%) were imaged at functional residual capacity, supine and prone, using magnetic resonance imaging, to quantify regional lung density. We defined regional gravitational stress as the cumulative weight, per unit area, of the column of lung tissue below each point. Gravitational stress was compared between regions of differing inflation to evaluate differences between highly stretched, and thus potentially vulnerable, regions and less stretched lung. Using reference density values for normal lungs at total lung capacity (0.10 ± 0.03 g/ml), regions were classified as highly inflated (density < 0.13 g/ml, i.e., close to total lung capacity), intermediate (0.13 ≤ density < 0.16 g/ml) or normally inflated (density ≥ 0.16 g/ml). Gravitational stress differed between inflation categories while supine (-1.6 ± 0.3 cmH2 O highly inflated; -1.4 ± 0.3 cmH2 O intermediate; -1.1 ± 0.1 cmH2 O normally inflated; P = 0.05) but not while prone (-1.4 ± 0.2 cmH2 O highly inflated; -1.3 ± 0.2 cmH2 O intermediate; -1.3 ± 0.1 cmH2 O normally inflated; P = 0.39), and increased more with height from dependent lung while supine (-0.24 ± 0.02 cmH2 O/cm supine; -0.18 ± 0.04 cmH2 O/cm prone; P = 0.05). In simulated severe pulmonary oedema, the gradient in gravitational stress increased in both postures (all P < 0.0001), was greater in the supine posture than when prone (-0.57 ± 0.21 cmH2 O/cm supine; -0.34 ± 0.16 cmH2 O/cm prone; P = 0.0004) and was similar to the gradient calculated from supine computed tomography images in a patient with acute respiratory distress syndrome (-0.51 cmH2 O/cm). The non-dependent lung has greater gravitational stress while supine and might be protected while prone, particularly in the presence of oedema.

Structural airway imaging metrics are differentially associated with persistent chronic bronchitis.

BACKGROUND: Chronic bronchitis (CB) is strongly associated with cigarette smoking, but not all smokers develop CB. We aimed to evaluate whether measures of structural airway disease on CT are differentially associated with CB. METHODS: In smokers between ages 45 and 80 years, and with Global Initiative for Obstructive Lung Disease stages 0-4, CB was defined by the classic definition. Airway disease on CT was quantified by (i) wall area percent (WA%) of segmental airways; (ii) Pi10, the square root of the wall area of a hypothetical airway with 10 mm internal perimeter; (iii) total airway count (TAC) and (iv) airway fractal dimension (AFD), a measure of the complex branching pattern and remodelling of airways. CB was also assessed at the 5-year follow-up visit. MEASUREMENTS AND MAIN RESULTS: Of 8917 participants, 1734 (19.4%) had CB at baseline. Airway measures were significantly worse in those with CB compared with those without CB: WA% 54.5 (8.8) versus 49.8 (8.3); Pi10 2.58 (0.67) versus 2.28 (0.59) mm; TAC 156.7 (81.6) versus 177.8 (91.1); AFD 1.477 (0.091) versus 1.497 (0.092) (all p<0.001). On follow-up of 5517 participants at 5 years, 399 (7.2%) had persistent CB. With adjustment for between-visits changes in smoking status and lung function, greater WA% and Pi10 were associated with significantly associated with persistent CB, adjusted OR per SD change 1.75, 95% CI 1.56 to 1.97; p<0.001 and 1.66, 95% CI 1.42 to 1.86; p<0.001, respectively. Higher AFD and TAC were associated with significantly lower odds of persistent CB, adjusted OR per SD change 0.76, 95% CI 0.67 to 0.86; p<0.001 and 0.69, 95% CI 0.60 to 0.80; p<0.001, respectively. CONCLUSIONS: Higher baseline AFD and TAC are associated with a lower risk of persistent CB, irrespective of changes in smoking status, suggesting preserved airway structure can confer a reserve against CB.

Assessment of drought with a real-time web-based application for drought management in humid tropical Kerala, India.

Geospatial techniques are useful for near real-time monitoring of drought and towards devising local-level effective drought management plan. Based on the historic and current remote sensing data, one can identify the influence of drought on the vegetation status by analyzing the anomaly/drought condition of a particular area of interest (AOI) through different digital image processing techniques. In this study, an attempt has been made to develop a web-based application for generating drought maps and district-wise drought information at real time in the web server using Hypertext Preprocessor (PHP) and Python scripts. A web-based application was developed and drought conditions existing in the study area were understood both spatially and temporally. The results of the application showed distinct variation of drought prevalence within the administrative boundaries. This web-based application was validated with drought analysis carried out using different drought indices, viz., standard precipitation index and reconnaissance drought index. The results established that this validated approach could be used for developing disaster management plan well in advance to combat the consequences of drought across the globe and to evolve strategic decisions which will have implications in the various sectors of the economy.

Different administration patterns of docosahexaenoic acid in combating cytotoxic manifestations due to arsenic trioxide (acute promyelocytic leukemia drug) induced redox imbalance in hepatocytes.

Docosahexaenoic acid (DHA) obtained from fish and plant sources is an essential dietary fatty acid and an important cell membrane structural component. The acute promyelocytic leukemia (APL) drug arsenic trioxide (As2O3), causes hepatotoxicity. We evaluated the protective potential of DHA as pre/combination/post-administration patterns against As2O3 induced toxicity. The therapeutic concentration of As2O3 (10 µM) resulted in cytotoxicity with a significant (p < 0.05) variation from the control group. Reduced cell viability, morphological alterations, enhanced LDH release and apoptosis were observed. The oxidative stress markers (lipid peroxidation, nitric oxide, and ROS) and hepatic enzymes (AST and ALT) and intracellular calcium levels were found to be elevated by the As2O3 administration. Reduction in levels of mitochondrial membrane potential, cellular free radical scavenging potential, intracellular proteins, ATPases and major antioxidants (catalase, SOD, GSH, and GPx) were also observed. Administration of DHA along with As2O3 as pre/combination administration patterns offered protection against As2O3 induced cytotoxicity at significant levels (p < 0.05) from As2O3 alone treated group. The cell viability and morphology were protected with reduced LDH release and apoptosis. The hepatic enzymes and oxidative stress markers were reduced with replenishment of mitochondrial membrane potential, free radical scavenging potential, intracellular proteins, ATPases and antioxidant levels. DHA pre/combination administration patterns showed protective potential against As2O3 with pre-treatment being the best and the post-treatment method failed to produce any protective effect.

Eugenol, a plant-derived phenolic nutraceutical, protects thiol (SH) group in myocardium from ROS-mediated oxidation under chemotherapeutic stress induced by arsenic trioxide - a in vivo model study.

Arsenic trioxide is an effective chemotherapeutic agent for the treatment of acute promyelocytic leukemia. The clinical usefulness of arsenic trioxide is narrow due to different organ toxicities. It is hypothesized that the generation of reactive oxygen species by arsenic trioxide leads to thiol-based oxidative damage in rat myocardium. In this study, the defensive effect of eugenol on thiol-based oxidative stress was investigated in arsenic trioxide-treated rats. Rats were orally administered with arsenic trioxide (4 mg/kg per day) alone and in combination with eugenol (5 mg/kg per day) for 30 days. Reduction in relative organ weight, total thiol level, protein thiol content, acid-soluble thiol content, thioredoxin activity, and protein content was witnessed in arsenic trioxide-treated rats. Additionally, the total antioxidant activity, tissue GSH level, and GSH/GSSG ratio were considerably diminished. However, the co-treatment of eugenol noticeably sheltered the arsenic trioxide-mediated cardiotoxicity. In conclusion, eugenol is a prospective phenolic compound, of natural origin, for protecting the thiol group in myocardium from oxidative stress by chemotherapeutic compounds.

Temporal and spatial variations of PM2.5 organic and elemental carbon in Central India.

This study describes spatiotemporal patterns from October 2015 to September 2016 for PM2.5 mass and carbon measurements in rural (Kosmarra), urban (Raipur), and industrial (Bhilai) environments, in Chhattisgarh, Central India. Twenty-four-hour samples were acquired once every other week at the rural and industrial sites. Twelve-hour daytime and nighttime samples were acquired either a once a week or once every other week at the urban site. Each site was equipped with two portable, battery-powered, miniVol air samplers with PM2.5 inlets. Annual average PM2.5 mass concentrations were 71.8 ± 27 µg m-3 at the rural site, 133 ± 51 µg m-3 at the urban site, and 244.5 ± 63.3 µg m-3 at the industrial site, ~ 2-6 times higher than the Indian Annual National Ambient Air Quality Standard of 40 µg m-3. Average monthly nighttime PM2.5 and carbon concentrations at the urban site were consistently higher than those of daytime from November 2015 to April 2016, when temperatures were low. Annual average total carbon (TC = OC + EC) at the urban (46.8 ± 23.8 µg m-3) and industrial (98.0 ± 17.2 µg m-3) sites also exceeded the Indian PM2.5 NAAQS. TC accounted for 30-40% of PM2.5 mass. Annual average OC ranged from 17.8 ± 6.1 µg m-3 at the rural site to 64 ± 9.4 µg m-3 at the industrial site, with EC ranging from 4.51 ± 2.2 to 34.01 ± 7.8 µg m-3. The average OC/EC ratio at the industrial site (1.88) was 18% lower than that at the urban site and 52% lower than that at the rural site. OC was attributed to 43.0% of secondary organic carbon (SOC) at the rural site, twice that estimated for the urban and industrial sites. Mortality burden estimates for PM2.5 EC are 4416 and 6196 excess deaths at the urban and industrial sites, respectively, during 2015-2016.

Flecainide challenge test: Predictors of unmasking of type 1 Brugada ECG pattern among those with non-type 1 Brugada ECG pattern.

BACKGROUND: Many subjects in community have non-type 1 Brugada pattern ECG with atypical symptoms, relevance of which is not clear. Provocative tests to unmask type 1 Brugada pattern in these patients would help in diagnosing Brugada Syndrome. However sensitivity and specificity of provocating drugs are variable. METHODS: We studied 29 patients referred to our institute with clinical presentation suggestive but not diagnostic of Brugada or with non-Type 1 Brugada pattern ECG. Flecainide Challenge Test (FCT) was done in these patients (IV Flecainide test in 4 patients and Oral Flecainide in 25 patients). Resting 12-lead ECG with standard precordial leads and ECG with precordial leads placed 1 Intercostal space above were performed after flecainide administration every 5 min for first 30 min and every 30 min thereafter until ECG became normal or upto 6 h. The positivity was defined as inducible Type 1 Brugada pattern in atleast 2 right sided leads. RESULT: Median age was 35(range = 5-65) years. In 16 (55%) patients the Type 1 Brugada pattern was unmasked. There were no episodes of major AV block, atrial or ventricular tachyarrhythmia. Three groups were considered for analysis: Group 1(n = 9) - FCT Positive among patients with non-type 1 Brugada ECG pattern, Group 2(n = 4) - FCT Negative among the patients with non-type 1 Brugada ECG pattern, and Group 3(n = 7) - FCT Positive among patients with no spontaneous Brugada ECG pattern. Binary logistic regression analysis found that family h/o SCD was predictive of FCT positivity in Group 1 (Odd's ratio 21, 95% Confidence interval 1.04 to 698.83, p = 0.004). CONCLUSION: Oral flecainide is useful and safe for unmasking of Type I Brugada pattern. In our study, among the many variables studied, family history of sudden cardiac death was the only predictor of flecainide test positivity among those with non-Type 1 Brugada pattern.

Acute outcome of treating patients admitted with electrical storm in a tertiary care centre.

BACKGROUND: Electrical storm (ES) is a life threatening emergency. There is little data available regarding acute outcome of ES. AIMS: The study aimed to analyze the acute outcome of ES, various treatment modalities used, and the factors associated with mortality. METHODS: This is a retrospective observational study involving patients admitted with ES at our centre between 1/1/2007 and 31/12/2013. RESULTS: 41 patients (mean age 54.61 ± 12.41 years; 86.7% males; mean ejection fraction (EF) 44.51 ± 16.48%) underwent treatment for ES. Hypokalemia (14.63%) and acute coronary syndrome (ACS) (14.63%) were the commonest identifiable triggers. Only 9 (21.95%) patients already had an ICD implanted. Apart from antiarrhythmic drugs (100%), deep sedation (87.8%), mechanical ventilation (24.39%) and neuraxial modulation using left sympathetic cardiac denervation (21.95%) were the common treatment modalities used. Thirty-three (80.49%) patients could be discharged after a mean duration of 14.2 ± 2.31 days. Eight (19.5%) patients died in hospital. The mortality was significantly higher in those with EF < 35% compared to those with a higher EF (8 (42.11% vs 0 (0%), p = 0.03)). There was no significant difference in mortality between those with versus without a structural heart disease (8 (21.1% vs 0 (0%), p = 0.32)). Comparison of mortality an ACS with ES versus ES of other aetiologies (3 (50%) vs 5 (14.29) %, p = 0.076)) showed a trend towards significance. CONCLUSION: With comprehensive treatment, there is reasonable acute survival rate of ES. Hypokalemia and ACS are the commonest triggers of ES. Patients with low EF and ACS have higher mortality.

Mitigation of hepatotoxic effects of arsenic trioxide through omega-3 fatty acid in rats.

Arsenic trioxide (As(2)O(3)) is an effective drug in the treatment of leukaemia and many solid tumours. In clinical trials, arsenic therapy is closely associated with hepatic toxicity. The present study was designed to investigate the efficacy of omega-3 fatty acid against As(2)O(3)-induced hepatotoxicity. A 4 mg/kg body weight (bw) of As(2)O(3) was orally administered to Wistar male rats for 45 days. Hepatotoxicity was evaluated by biochemical tests, antioxidant assays and histopathological examinations. Arsenic accumulation was found in the liver tissue of rats treated with As(2)O(3). Hepatoprotective efficacy of omega-3 fatty acid was analysed by the combination therapy with As(2)O(3). In vivo studies revealed a significant rise in lipid peroxidation with concomitant decline in reduced glutathione, glutathione-dependant antioxidant enzymes and antiperoxidative enzymes in the liver tissue of rats treated with arsenic. The supplementation of omega-3 fatty acid at a dose of 50 mg/kg bw with As(2)O(3) offers ameliorative effect against hepatocellular toxicity. Omega-3 fatty acid maintained hepatic marker enzymes, antioxidant enzymes and decreased lipid peroxidation. The combination treatment clearly reduced the hepatic structural abnormalities such as haemorrhage, necrosis and cholangiofibrosis in the rats treated with arsenic. This study concludes that the omega-3 fatty acid might be useful for the protection against As(2)O(3)-induced hepatotoxicity.

Assessing the pulmonary vascular responsiveness to oxygen with proton MRI.

Ventilation-perfusion matching occurs passively and is also actively regulated through hypoxic pulmonary vasoconstriction (HPV). The extent of HPV activity in humans, particularly normal subjects, is uncertain. Current evaluation of HPV assesses changes in ventilation-perfusion relationships/pulmonary vascular resistance with hypoxia and is invasive, or unsuitable for patients because of safety concerns. We used a noninvasive imaging-based approach to quantify the pulmonary vascular response to oxygen as a metric of HPV by measuring perfusion changes between breathing 21% and 30%O2 using arterial spin labeling (ASL) MRI. We hypothesized that the differences between 21% and 30%O2 images reflecting HPV release would be 1) significantly greater than the differences without [Formula: see text] changes (e.g., 21-21% and 30-30%O2) and 2) negatively associated with ventilation-perfusion mismatch. Perfusion was quantified in the right lung in normoxia (baseline), after 15 min of 30% O2 breathing (hyperoxia) and 15 min normoxic recovery (recovery) in healthy subjects (7 M, 7 F; age = 41.4 ± 19.6 yr). Normalized, smoothed, and registered pairs of perfusion images were subtracted and the mean square difference (MSD) was calculated. Separately, regional alveolar ventilation and perfusion were quantified from specific ventilation, proton density, and ASL imaging; the spatial variance of ventilation-perfusion (σ2V̇a/Q̇) distributions was calculated. The O2-responsive MSD was reproducible (R2 = 0.94, P < 0.0001) and greater (0.16 ± 0.06, P < 0.0001) than that from subtracted images collected under the same [Formula: see text] (baseline = 0.09 ± 0.04, hyperoxia = 0.08 ± 0.04, recovery = 0.08 ± 0.03), which were not different from one another (P = 0.2). The O2-responsive MSD was correlated with σ2V̇a/Q̇ (R2 = 0.47, P = 0.007). These data suggest that active HPV optimizes ventilation-perfusion matching in normal subjects. This noninvasive approach could be applied to patients with different disease phenotypes to assess HPV and ventilation-perfusion mismatch.NEW & NOTEWORTHY We developed a new proton MRI method to noninvasively quantify the pulmonary vascular response to oxygen. Using a hyperoxic stimulus to release HPV, we quantified the resulting redistribution of perfusion. The differences between normoxic and hyperoxic images were greater than those between images without [Formula: see text] changes and negatively correlated with ventilation-perfusion mismatch. This suggests that active HPV optimizes ventilation-perfusion matching in normal subjects. This approach is suitable for assessing patients with different disease phenotypes.

Myocardial toxicity of acute promyelocytic leukaemia drug-arsenic trioxide.

BACKGROUND: Arsenic trioxide (As2O3) is an environmental toxicant as well as an effective anti cancer agent against many types of cancers. It is a promising drug for patients with relapsed acute promyelocytic leukaemia (APL), but its clinical efficacy is burdened by the serious cardiac toxicities. AIM: The present study was designed to investigate the toxic mechanism of arsenic in cardiac tissue at its clinically relevant concentrations. MATERIALS AND METHODS: Experimental rats were administered with As2O3 2, 4 and 8 mg/kg body weight, orally for a period of 45 days. Cardiac toxicities were recorded by lipid peroxidation, activities of glutathione dependent antioxidant and antiperoxidative enzymes, cardiac arsenic accumulation and histopathological changes. RESULTS: In vivo studies revealed a significant rise in lipid peroxidation, decline in reduced glutathione, glutathione dependent antioxidant enzymes and antiperoxidative enzymes in the cardiac tissue of arsenic treated rats. The extent of free radical production was found increased with periodic rise in the arsenic concentration. The experimental group which received 8 mg/kg body weight of arsenic exhibited the highest deposition of arsenic in cardiac tissue. Light microscopic examination of cardiac tissues in arsenic treated rats has showed increased structural abnormalities like myocardial fibre swelling, capillary congestion and micro-haemorrhages. CONCLUSIONS: The study concludes that the mechanism of arsenic induced cardiac toxicity is associated with the accumulation of arsenic in tissue and the extent of free radical production.

Changes in the thermodynamical profiles of the subsurface ocean and atmosphere induce cyclones to congregate over the Eastern Arabian Sea.

The Arabian Sea accounts for a small fraction of Tropical Cyclones-about 2% of the annual global mean. However, the damage they might inflict there and along its coastlines, which are thickly populated, is considerable. This study explores the influence of the changes in the vertical profiles of atmosphere and oceanic environment throughout the seasons of March-June (MAMJ) and October-December (OND) in clustering the cyclogenesis over the Eastern Arabian Sea (EAS) next to the Indian West coast in recent decades. Further investigation has been done into the precise contribution of atmospheric and oceanic factors to fluctuations in cyclone intensity throughout the MAMJ and OND seasons separately. Two seasons have been studied independently in order to better understand the distinct influences of the vertical fluctuation of atmospheric factors and the thermal structure of the oceanic subsurface on cyclogenesis. More severe cyclones are caused by high tropical cyclone heat potential, and ocean subsurface warming present in this sea region influences the genesis of storms mostly during MAMJ. On the other hand, mid tropospheric relative humidity and thermal instability influences more on increasing cyclogenesis and its clustering over EAS during OND season. The findings suggest that large-scale oceanic subsurface conditions have a crucial influence on cyclogenesis over EAS through oceanic sensitivity to atmospheric forcing. This cyclone tendency and its clustering over EAS needs attention in terms of forecasting, catastrophe risk reduction, and climate change adaptation due to the security of coastal urban and rural habitats, livelihoods, and essential infrastructure along the coasts.

Non-monolithic fabrication of thin-film microelectrode arrays on PMUT transducers as a bimodal neuroscientific investigation tool.

Ultrasound (US)-based neuromodulation has recently emerged as a spatially selective yet non-invasive alternative to conventional electrically-based neural interfaces. However, the fundamental mechanisms of US neuromodulation are not yet clarified. Thus, there is a need for in-vitro bimodal investigation tools that allow us to compare the effect of US versus electrically-induced neural activity in the vicinity of the transducing element. To this end, we propose a MicroElectrode-MicroTransducer Array (MEMTA), where a dense array of electrodes is co-fabricated on top of a similarly dense array of US transducers.In this paper, we test the proof of concept for such co-fabrication using a non-monolithic approach, where, at its most challenging scenario, desired topologies require electrodes to be formed directly on top of fragile piezoelectric micromachined ultrasound transducer (PMUTs) membranes. On top of the PMUTs, a thin-film microelectrode array was developed utilizing microfabrication processes, including metal sputtering, lithography, etching and soft encapsulation. The samples were analysed through focused ion beam-scanning electron microscopy (FIB-SEM), and the results have shown that damage to the membranes does not occur during any of the process steps. This paper proves that the non-monolithic development of a miniaturised bimodal neuroscientific investigation tool can be achieved, thus, opening up a series of possibilities for further understanding and investigation of the nervous system.

The spatial-temporal dynamics of pulmonary blood flow are altered in pulmonary arterial hypertension.

Global fluctuation dispersion (FDglobal), a spatial-temporal metric derived from serial images of the pulmonary perfusion obtained with MRI-arterial spin labeling, describes temporal fluctuations in the spatial distribution of perfusion. In healthy subjects, FDglobal is increased by hyperoxia, hypoxia, and inhaled nitric oxide. We evaluated patients with pulmonary arterial hypertension (PAH, 4F, aged 47 ± 15, mean pulmonary artery pressure 48 ± 7 mmHg) and healthy controls (CON, 7F, aged 47 ± 12) to test the hypothesis that FDglobal is increased in PAH. Images were acquired at ∼4-5 s intervals during voluntary respiratory gating, inspected for quality, registered using a deformable registration algorithm, and normalized. Spatial relative dispersion (RD = SD/mean) and the percent of the lung image with no measurable perfusion signal (%NMP) were also assessed. FDglobal was significantly increased in PAH (PAH = 0.40 ± 0.17, CON = 0.17 ± 0.02, P = 0.006, a 135% increase) with no overlap in values between the two groups, consistent with altered vascular regulation. Both spatial RD and %NMP were also markedly greater in PAH vs. CON (PAH RD = 1.46 ± 0.24, CON = 0.90 ± 0.10, P = 0.0004; PAH NMP = 13.4 ± 6.1%; CON = 2.3 ± 1.4%, P = 0.001 respectively) consistent with vascular remodeling resulting in poorly perfused regions of lung and increased spatial heterogeneity. The difference in FDglobal between normal subjects and patients with PAH in this small cohort suggests that spatial-temporal imaging of perfusion may be useful in the evaluation of patients with PAH. Since this MR imaging technique uses no injected contrast agents and has no ionizing radiation it may be suitable for use in diverse patient populations.NEW & NOTEWORTHY Using proton MRI-arterial spin labeling to obtain serial images of pulmonary perfusion, we show that global fluctuation dispersion (FDglobal), a metric of temporal fluctuations in the spatial distribution of perfusion, was significantly increased in female patients with pulmonary arterial hypertension (PAH) compared with healthy controls. This potentially indicates pulmonary vascular dysregulation. Dynamic measures using proton MRI may provide new tools for evaluating individuals at risk of PAH or for monitoring therapy in patients with PAH.

Imaging-based assessment of lung function in a population cooking indoors with biomass fuel: a pilot study.

Biomass fuels (wood) are commonly used indoors in underventilated environments for cooking in the developing world, but the impact on lung physiology is poorly understood. Quantitative computed tomography (qCT) can provide sensitive metrics to compare the lungs of women cooking with wood vs. liquified petroleum gas (LPG). We prospectively assessed (qCT and spirometry) 23 primary female cooks (18 biomass, 5 LPG) with no history of cardiopulmonary disease in Thanjavur, India. CT was obtained at coached total lung capacity (TLC) and residual volume (RV). qCT assessment included texture-derived ground glass opacity [GGO: Adaptive Multiple Feature Method (AMFM)], air-trapping (expiratory voxels ≤ -856HU) and image registration-based assessment [Disease Probability Measure (DPM)] of emphysema, functional small airways disease (%AirTrapDPM), and regional lung mechanics. In addition, within-kitchen exposure assessments included particulate matter <2.5 µm(PM2.5), black carbon, ß-(1, 3)-d-glucan (surrogate for fungi), and endotoxin. Air-trapping went undetected at RV via the threshold-based measure (voxels ≤ -856HU), possibly due to density shifts in the presence of inflammation. However, DPM, utilizing image-matching, demonstrated significant air-trapping in biomass vs. LPG cooks (P = 0.049). A subset of biomass cooks (6/18), identified using k-means clustering, had markedly altered DPM-metrics: greater air-trapping (P < 0.001), lower TLC-RV volume change (P < 0.001), a lower mean anisotropic deformation index (ADI; P < 0.001), and elevated % GGO (P < 0.02). Across all subjects, a texture measure of bronchovascular bundles was correlated to the log-transformed ß-(1, 3)-d-glucan concentration (P = 0.026, R = 0.46), and black carbon (P = 0.04, R = 0.44). This pilot study identified environmental links with qCT-based lung pathologies and a cluster of biomass cooks (33%) with significant small airways disease.NEW & NOTEWORTHY Quantitative computed tomography has identified a cluster of women (33%) cooking with biomass fuels (wood) with image-based markers of functional small airways disease and associated alterations in regional lung mechanics. Texture and image registration-based metrics of lung function may allow for early detection of potential inflammatory processes that may arise in response to inhaled biomass smoke, and help identify phenotypes of chronic lung disease prevalent in nonsmoking women in the developing world.

Development of 187Re targets for heavy ion induced reactions.

To perform nuclear reaction experiment, very good quality, uniform and thin targets are necessary. In order to carry out evaporation residue cross section measurement of 19F+187Re reaction using Hybrid Recoil mass Analyzer (HYRA) facility at Inter - University Accelerator Center (IUAC) 187Re targets of thickness 200 µg/cm2 are required. More than 20 targets of 187Re of 200 µg/cm2 thickness with thin carbon backing have been prepared using 70 mg of 187Re. Being one of the highest melting points of all elements, high temperature involved in the process and limited amount of available isotopic material are the major constraints during the target development of 187Re. The targets have been successfully used for the nuclear reaction experiment. The method used for the development of several 187Re targets with minimum material consumption and the detailed characterization techniques applied for studying the targets are discussed in detail.

Vaping disrupts ventilation-perfusion matching in asymptomatic users.

Inhalation of e-cigarette's aerosols (vaping) has the potential to disrupt pulmonary gas exchange, but the effects in asymptomatic users are unknown. We assessed ventilation-perfusion (V̇A/Q̇) mismatch in asymptomatic e-cigarette users, using magnetic resonance imaging (MRI). We hypothesized that vaping induces V̇A/Q̇ mismatch through alterations in both ventilation and perfusion distributions. Nine young, asymptomatic "Vapers" with >1-yr vaping history, and no history of cardiopulmonary disease, were imaged supine using proton MRI, to assess the right lung at baseline and immediately after vaping. Seven young "Controls" were imaged at baseline only. Relative dispersion (SD/means) was used to quantify the heterogeneity of the individual ventilation and perfusion distributions. V̇A/Q̇ mismatch was quantified using the second moments of the ventilation and perfusion versus V̇A/Q̇ ratio distributions, log scale, LogSDV̇, and LogSDQ̇, respectively, analogous to the multiple inert gas elimination technique. Spirometry was normal in both groups. Ventilation heterogeneity was similar between groups at baseline (Vapers, 0.43 ± 0.13; Controls, 0.51 ± 0.11; P = 0.13) but increased after vaping (to 0.57 ± 0.17; P = 0.03). Perfusion heterogeneity was greater (P = 0.04) in Vapers at baseline (0.53 ± 0.06) compared with Controls (0.44 ± 0.10) but decreased after vaping (to 0.42 ± 0.07; P = 0.005). Vapers had greater (P = 0.01) V̇A/Q̇ mismatch at baseline compared with Controls (LogSDQ̇ = 0.61 ± 0.12 vs. 0.43 ± 0.12), which was increased after vaping (LogSDQ̇ = 0.73 ± 0.16; P = 0.03). V̇A/Q̇ mismatch is greater in Vapers and worsens after vaping. This suggests subclinical alterations in lung function not detected by spirometry.NEW & NOTEWORTHY This research provides evidence of vaping-induced disruptions in ventilation-perfusion matching in young, healthy, asymptomatic adults with normal spirometry who habitually vape. The changes in ventilation and perfusion distributions, both at baseline and acutely after vaping, and the potential implications on hypoxic vasoconstriction are particularly relevant in understanding the pathogenesis of vaping-induced dysfunction. Our imaging-based approach provides evidence of potential subclinical alterations in lung function below thresholds of detection using spirometry.

Development of novel chitin/nanosilver composite scaffolds for wound dressing applications.

Antibiotic resistance of microorganisms is one of the major problems faced in the field of wound care and management resulting in complications like infection and delayed wound healing. Currently a lot of research is focused on developing newer antimicrobials to treat wounds infected with antibiotic resistant microorganisms. Silver has been used as an antimicrobial agent for a long time in the form of metallic silver and silver sulfadiazine ointments. Recently silver nanoparticles have come up as a potent antimicrobial agent and are finding diverse medical applications ranging from silver based dressings to silver coated medical devices. Chitin is a natural biopolymer with properties like biocompatibility and biodegradability. It is widely used as a scaffold for tissue engineering applications. In this work, we developed and characterized novel chitin/nanosilver composite scaffolds for wound healing applications. The antibacterial, blood clotting and cytotoxicity of the prepared composite scaffolds were also studied. These chitin/nanosilver composite scaffolds were found to be bactericidal against S. aureus and E. coli and good blood clotting ability. These results suggested that these chitin/nanosilver composite scaffolds could be used for wound healing applications.