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.

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.

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.

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.

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.

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.

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.

Ventilation-perfusion heterogeneity measured by the multiple inert gas elimination technique is minimally affected by intermittent breathing of 100% O2.

Proton magnetic resonance (MR) imaging to quantify regional ventilation-perfusion ( V˙A/Q˙ ) ratios combines specific ventilation imaging (SVI) and separate proton density and perfusion measures into a composite map. Specific ventilation imaging exploits the paramagnetic properties of O2 , which alters the local MR signal intensity, in an FI O2 -dependent manner. Specific ventilation imaging data are acquired during five wash-in/wash-out cycles of breathing 21% O2 alternating with 100% O2 over ~20 min. This technique assumes that alternating FI O2 does not affect V˙A/Q˙ heterogeneity, but this is unproven. We tested the hypothesis that alternating FI O2 exposure increases V˙A/Q˙ mismatch in nine patients with abnormal pulmonary gas exchange and increased V˙A/Q˙ mismatch using the multiple inert gas elimination technique (MIGET).The following data were acquired (a) breathing air (baseline), (b) breathing alternating air/100% O2 during an emulated-SVI protocol (eSVI), and (c) 20 min after ambient air breathing (recovery). MIGET heterogeneity indices of shunt, deadspace, ventilation versus V˙A/Q˙ ratio, LogSD V˙ , and perfusion versus V˙A/Q˙ ratio, LogSD Q˙ were calculated. LogSD V˙ was not different between eSVI and baseline (1.04 ± 0.39 baseline, 1.05 ± 0.38 eSVI, p = .84); but was reduced compared to baseline during recovery (0.97 ± 0.39, p = .04). There was no significant difference in LogSD Q˙ across conditions (0.81 ± 0.30 baseline, 0.79 ± 0.15 eSVI, 0.79 ± 0.20 recovery; p = .54); Deadspace was not significantly different (p = .54) but shunt showed a borderline increase during eSVI (1.0% ± 1.0 baseline, 2.6% ± 2.9 eSVI; p = .052) likely from altered hypoxic pulmonary vasoconstriction and/or absorption atelectasis. Intermittent breathing of 100% O2 does not substantially alter V˙A/Q˙ matching and if SVI measurements are made after perfusion measurements, any potential effects will be minimized.

Pretreatment of Tribulus terrestris L. causes anti-ischemic cardioprotection through MAPK mediated anti-apoptotic pathway in rat.

The aim of the present investigation is the evaluation and elucidation of the mechanisms by which Tribulus terrestris L. methanol extract (TTM) devoid of fruit exhibits protection against cardiac ischemia in in vitro (H9c2 cell line) and in vivo (Wistar rat) model. Tribulus terrestris L. (TT) was used in this study to evaluate the efficacy against cardiac ischemia employing in vitro and in vivo models of myocardial ischemia. H9c2 cells were used for the in vitro induction of ischemia. Male Wistar rats (10 weeks old) weighing 180-220 g were used for the in vivo experiments. ECG and clinically relevant cardiac biomarkers like serum lactate dehydrogenase, serum creatinine kinase, serum creatinine kinase myocardial B fraction, serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase were analysed to evaluate efficacy in the rat. For elucidation of molecular mechanisms of its beneficial activity in vitro, expression of apoptotic markers like Bax, Bad, Bcl-2 and signalling pathways involving mitogen-activated protein kinases like p38α, JNK, and Akt were studied. Tribulus terrestris L. was found effective against cardiac ischemia in the rat which was evident from ECG and various cardiac biomarkers analysis. Tribulus terrestris L. was found to act through the mitogen-activated signalling pathway leading to prevention of apoptosis during ischemic insult. The beneficial effect of Tribulus terrestris L. against cardiac ischemia was seen both in in vitro and in vivo models via its anti-apoptotic potential.

Household solid fuel burning emission characterization and activity levels in India.

Emission factors (EFs) of PM2.5, carbon fractions, major ionic (K+, Ca2+, NH4+, SO42-, NO3- and Cl-) and elemental (Al, Cr, Cu and Fe) species from combustion of commonly used household solid fuel were determined in 10 different states in India during cooking practices. The study involved sampling during actual household cooking involving use of a variety of fuels including coal balls (CB), fuel wood (FW), dung cakes (DC), crop residues (CR), mixed fuels (MF: dung cakes + fuel woods). Species-wise highest EFs (g·kg-1) were: 34.16 ±â€¯10.1 for PM2.5 (CB), 14.18 ±â€¯5.8 for OC (CB), 2.33 ±â€¯1.4 for EC (DC), 1.03 ±â€¯0.2 for K+ (CR), 2.21 ±â€¯0.6 NH4+ (DC), 0.61 ±â€¯0.2 for NO3- (CB), 0.59 ±â€¯0.1 for SO42- (CB), 0.69 ±â€¯0.1 for Cl- (CR) among the fuels. Higher OC EFs for CB could be attributed to higher moisture content (>13%) in coal-powder that is used to handmade coal balls. It is observed that, in general, OC3 and EC1 were the dominant thermally evolved carbon mass fractions. The study averaged MCE values were in the range 0.93-0.98, which could be attributed to higher variability in flaming and smoldering episodes during the combustion of selected fuels. Sum of ionic EFs for emissions from DC, CR and MF were found to be higher than those observed for FW and CB. The K+/EC and Cl-/EC (~1) ratios could be better indicators of CR fuels to differentiate it from FW, whereas NH4+/EC (~1) is suitable to indicate DC. Average annual emission estimates of PM2.5 (2.00 ±â€¯0.53 Tg·yr-1), OC (0.86 ±â€¯0.23 Tg·yr-1) and EC (0.11 ±â€¯0.02 Tg·yr-1) for tested fuels are evaluated to be contributing 27, 15 and 4% of total PM2.5, OC and EC, respectively, toward annual emission budget from different anthropogenic activities in India.

Airway fractal dimension predicts respiratory morbidity and mortality in COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by airway remodeling. Characterization of airway changes on computed tomography has been challenging due to the complexity of the recurring branching patterns, and this can be better measured using fractal dimensions. METHODS: We analyzed segmented airway trees of 8,135 participants enrolled in the COPDGene cohort. The fractal complexity of the segmented airway tree was measured by the Airway Fractal Dimension (AFD) using the Minkowski-Bougliand box-counting dimension. We examined associations between AFD and lung function and respiratory morbidity using multivariable regression analyses. We further estimated the extent of peribronchial emphysema (%) within 5 mm of the airway tree, as this is likely to affect AFD. We classified participants into 4 groups based on median AFD, percentage of peribronchial emphysema, and estimated survival. RESULTS: AFD was significantly associated with forced expiratory volume in one second (FEV1; P < 0.001) and FEV1/forced vital capacity (FEV1/FVC; P < 0.001) after adjusting for age, race, sex, smoking status, pack-years of smoking, BMI, CT emphysema, air trapping, airway thickness, and CT scanner type. On multivariable analysis, AFD was also associated with respiratory quality of life and 6-minute walk distance, as well as exacerbations, lung function decline, and mortality on longitudinal follow-up. We identified a subset of participants with AFD below the median and peribronchial emphysema above the median who had worse survival compared with participants with high AFD and low peribronchial emphysema (adjusted hazards ratio [HR]: 2.72; 95% CI: 2.20-3.35; P < 0.001), a substantial number of whom were not identified by traditional spirometry severity grades. CONCLUSION: Airway fractal dimension as a measure of airway branching complexity and remodeling in smokers is associated with respiratory morbidity and lung function change, offers prognostic information additional to traditional CT measures of airway wall thickness, and can be used to estimate mortality risk. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00608764. FUNDING: This study was supported by NIH K23 HL133438 (SPB) and the COPDGene study (NIH Grant Numbers R01 HL089897 and R01 HL089856). The COPDGene project is also supported by the COPD Foundation through contributions made to an Industry Advisory Board comprised of AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer, Siemens, Sunovion and GlaxoSmithKline.

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.

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.

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.

Multifocal Presentation of a Laryngeal Disorder.

Multifocal presentation of a laryngeal disorder is very rare. We report a case of a 48-year-old man, who presented to our hospital with hoarse voice for two years. Stroboscopic evaluation followed by surgery was done and the specimens were sent for histopathological examination from three different anatomical sites of larynx which were diagnosed as one-benign lesion, second-benign lesion but ability of malignant transformation and the third-a malignancy.