bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of atorvastatin metabolites on induction of drug‐metabolizing enzymes and membrane transporters through human pregnane X receptor
Authors: Hoffart E , Ghebreghiorghis L , Nussler AK , Thasler WE , Weiss TS , Schwab M , Burk O 
Published: September 2011

BACKGROUND AND PURPOSE Atorvastatin metabolites differ in their potential for drug interaction because of differential inhibition of drug‐metabolizing enzymes and transporters. We here investigate whether they exert differential effects on the induction of these genes via activation of pregnane X receptor (PXR) and constitutive androstane receptor (CAR).EXPERIMENTAL APPROACH Ligand binding to PXR or CAR was analysed by mammalian two‐hybrid assembly and promoter/reporter gene assays. Additionally, surface plasmon resonance was used to analyse ligand binding to CAR. Primary human hepatocytes were treated with atorvastatin metabolites, and mRNA and protein expression of PXR‐regulated genes was measured. Two‐hybrid co‐activator interaction and co‐repressor release assays were utilized to elucidate the molecular mechanism of PXR activation.KEY RESULTS All atorvastatin metabolites induced the assembly of PXR and activated CYP3A4 promoter activity. Ligand binding to CAR could not be proven. In primary human hepatocytes, the para‐hydroxy metabolite markedly reduced or abolished induction of cytochrome P450 and transporter genes. While significant differences in co‐activator recruitment were not observed, para‐hydroxy atorvastatin demonstrated only 50% release of co‐repressors.CONCLUSIONS AND IMPLICATIONS Atorvastatin metabolites are ligands of PXR but not of CAR. Atorvastatin metabolites demonstrate differential induction of PXR target genes, which results from impaired release of co‐repressors. Consequently, the properties of drug metabolites have to be taken into account when analysing PXR‐dependent induction of drug metabolism and transport. The drug interaction potential of the active metabolite, para‐hydroxy atorvastatin, might be lower than that of the parent compound.
Roflumilast inhibits the release of chemokines and TNF‐α from human lung macrophages stimulated with lipopolysaccharide
Authors: Buenestado A , Grassin‐Delyle S , Guitard F , Naline E , Faisy C , Israël‐Biet D , Sage E , Bellamy JF , Tenor H , Devillier P 
Published: September 2011

BACKGROUND AND PURPOSE Lung macrophages are critically involved in respiratory diseases. This study assessed the effects of the PDE4 inhibitor roflumilast and its active metabolite, roflumilast N‐oxide on the release of a range of chemokines (CCL2, 3, 4, CXCL1, 8, 10) and of TNF‐α, from human lung macrophages, stimulated with bacterial lipopolysaccharide LPS.EXPERIMENTAL APPROACH Lung macrophages isolated from resected human lungs were incubated with roflumilast, roflumilast N‐oxide, PGE2, the COX inhibitor indomethacin, the COX‐2 inhibitor NS‐398 or vehicle and stimulated with LPS (24 h). Chemokines, TNF‐α, PGE2 and 6‐keto PGF1α were measured in culture supernatants by immunoassay. COX‐2 mRNA expression was assessed with RT‐qPCR. PDE activities were determined in macrophage homogenates.KEY RESULTS Expression of PDE4 in lung macrophages was increased after incubation with LPS. Roflumilast and roflumilast N‐oxide concentration‐dependently reduced the LPS‐stimulated release of CCL2, CCL3, CCL4, CXCL10 and TNF‐α from human lung macrophages, whereas that of CXCL1 or CXCL8 was not altered. This reduction by the PDE4 inhibitors was further accentuated by exogenous PGE2 (10 nM) but abolished in the presence of indomethacin or NS‐398. Conversely, addition of PGE2 (10 nM), in the presence of indomethacin restored inhibition by roflumilast. LPS also increased PGE2 and 6‐keto PGF1α release from lung macrophages which was associated with an up‐regulation of COX‐2 mRNA.CONCLUSIONS AND IMPLICATIONS Roflumilast and roflumilast N‐oxide reduced LPS‐induced release of CCL2, 3, 4, CXCL10 and TNF‐α in human lung macrophages.
Categorizing the Effect of Comorbidity: A Qualitative Study of Individuals’ Experiences in a Low‐Vision Rehabilitation Program
Authors: Whitson Heather E. , Steinhauser Karen , Ammarell Natalie , Whitaker Diane , Cousins Scott W. , Ansah Deidra , Sanders Linda L. , Cohen Harvey J. 
Published: September 2011

ObjectivesTo identify generalizable ways that comorbidity affects older adults’ experiences in a health service program directed toward an index condition and to develop a framework to assist clinicians in approaching comorbidity in the design, delivery, and evaluation of such interventions.DesignA qualitative data content analysis of interview transcripts to identify themes related to comorbidity.SettingAn outpatient low‐vision rehabilitation program for macular disease.ParticipantsIn 2007/08, 98 individuals undergoing low‐vision rehabilitation and their companions provided 624 semistructured interviews that elicited perceptions about barriers and facilitators of successful program participation.ResultsThe interviews revealed five broad themes about comorbidity: (i) “good days, bad days,” reflecting participants’ fluctuating health status during the program because of concurrent medical problems; (ii) “communication barriers.” which were sometimes due to participant impairments and sometimes situational; (iii) “overwhelmed,” which encompassed pragmatic and emotional concerns of participants and caregivers; (iv) “delays,” which referred to the tendency of comorbidities to delay progress in the program and to confer added inconvenience during lengthy appointments; and (v) value of companion involvement in overcoming some barriers imposed by comorbid conditions.ConclusionThis study provides a taxonomy and conceptual framework for understanding consequences of comorbidity in the experience of individuals receiving a health service. If confirmed in individuals receiving interventions for other index diseases, the framework suggests actionable items to improve care and facilitate research involving older adults.
Mechanical Esophageal Displacement During Catheter Ablation for Atrial Fibrillation
Authors: KORUTH JACOB S. , REDDY VIVEK Y. , MILLER MARC A. , PATEL KALPESH K. , COFFEY JAMES O. , FISCHER AVI , GOMES J. ANTHONY , DUKKIPATI SRINIVAS , D’AVILA ANDRE , MITTNACHT ALEXANDER 
Published: September 2011

Esophageal Deviation in AF Ablation.Objective:To determine the feasibility and safety of esophageal displacement during atrial fibrillation (AF) ablation, to prevent thermal injury.Background:Patients undergoing AF ablation are at risk of esophageal thermal injury, which ranges from superficial ulceration, to gastroparesis, to the rare but catastrophic atrioesophageal fistula. A common approach to avoid damage is luminal esophageal temperature (LET) monitoring; however, (1) temperature rises mandate interruptions in energy delivery that interrupt workflow and potentially decrease procedural efficacy, and (2) esophageal fistulas have been reported even with LET monitoring.Methods:A cohort of 20 consecutive patients undergoing radiofrequency (RF) (16 patients) or laser balloon (4 patients) ablation of AF under general anesthesia. After barium instillation, the esophagus was deviated using an endotracheal stylet placed within a thoracic chest tube. LET monitoring was used during catheter ablation. Upper GI endoscopy was performed prior to discharge.Results:At the pulmonary vein level, leftward deviation measured 2.8 ± 1.6 cm (range: 0.4–5.7) and rightward deviation 2.8 ± 1.8 cm (range: 0.5–4.9). The temperature rose to >38.5 °C in 3/20 (15%) patients. In these 3 patients, there was an average of 2 applications/patient that recorded temperatures >38.5 °C. No patient had a temperature rise > 40 °C. Endoscopy revealed no esophageal ulceration from thermal injury in 18/19 (95%) patients; the sole patient with a thermally mediated ulceration had an unusual esophageal diverticulum fully across the posterior left atrium. Twelve patients (63%) exhibited trauma related to instrumentation with no clinical sequelae.Conclusions:Mechanical esophageal deviation is feasible and allows for uninterrupted energy delivery along the posterior wall during catheter ablation of AF.J Cardiovasc Electrophysiol, Vol. 23, pp. 147‐154, February 2012)
Accelerating EPI Distortion Correction by Utilizing a Modern GPU‐Based Parallel Computation
Authors: Yang Yao‐Hao , Huang Teng‐Yi , Wang Fu‐Nien , Chuang Tzu‐Chao , Chen Nan‐Kuei 
Published: September 2011

ABSTRACTBACKGROUND AND PURPOSEThe combination of phase demodulation and field mapping is a practical method to correct echo planar imaging (EPI) geometric distortion. However, since phase dispersion accumulates in each phase‐encoding step, the calculation complexity of phase modulation is Ny‐fold higher than conventional image reconstructions. Thus, correcting EPI images via phase demodulation is generally a time‐consuming task.METHODSParallel computing by employing general‐purpose calculations on graphics processing units (GPU) can accelerate scientific computing if the algorithm is parallelized. This study proposes a method that incorporates the GPU‐based technique into phase demodulation calculations to reduce computation time. The proposed parallel algorithm was applied to a PROPELLER‐EPI diffusion tensor data set.RESULTSThe GPU‐based phase demodulation method reduced the EPI distortion correctly, and accelerated the computation. The total reconstruction time of the 16‐slice PROPELLER‐EPI diffusion tensor images with matrix size of 128 × 128 was reduced from 1,754 seconds to 101 seconds by utilizing the parallelized 4‐GPU program.CONCLUSIONSGPU computing is a promising method to accelerate EPI geometric correction. The resulting reduction in computation time of phase demodulation should accelerate postprocessing for studies performed with EPI, and should effectuate the PROPELLER‐EPI technique for clinical practice.
Sudden oak death disease progression across two forest types and spatial scales
Authors: Ramage Benjamin S. , Forrestel Alison B. , Moritz Max A. , O'Hara Kevin L. 
Published: September 2011

AbstractQuestionsHow is sudden oak death disease progression affected by forest type? Which specific factors influence mortality rates and patterns? How do these trends vary across spatial scales?LocationPoint Reyes National Seashore, California,USA.MethodsSudden oak death, caused by the exotic pathogenPhytophthora ramorum, is affecting forests throughout coastal California. We investigated disease progression in tanoak (Notholithocarpus densiflorussyn.Lithocarpus densiflorus), the most susceptible species, in two distinct forest types: coast redwood (Sequoia sempervirens) and Douglas‐fir (Pseudotsuga menziesiivar.menziesii). Within each forest type, we used a variant of a split‐plot design to sample proximate areas at two different stages of disease progression (relatively unaffected vs severely impacted), and used generalized linear mixed effects models to analyse these data.ResultsAnnual mortality rates were much higher in Douglas‐fir (10.1–26.2%) than in redwood (3.2–8.2%) forest, and data suggested that similarly divergent rates will continue into the future (proportions of surviving trees with disease symptoms remained constant from the beginning to the end of the study period). Across both forest types, survival probabilities were lower for tanoaks with larger diameters and tanoaks in plots (1/20 ha) and neighbourhoods (3‐m radius) with greater basal area of previously killed tanoak. All variables were significant when included in the same model, suggesting that disease spread is occurring simultaneously at two local spatial scales. Several other biotic and abiotic variables were unrelated to tanoak survival probability.ConclusionsWe detected mortality rates that exceed any rates previously associated with sudden oak death, while demonstrating that these rates can vary substantially between adjacent forest types. However, because the Douglas‐fir forests of our study area are adjacent to the ocean, which is somewhat uncommon for this forest type, our findings do not necessarily indicate that all Douglas‐fir forests with a substantial tanoak component are at risk of similar impacts. Our data also suggest that, in both forest types, local patchiness in disease presence/severity is an ephemeral condition resulting primarily from stochastic processes (e.g. long‐distance dispersal events), while intra‐plot spread around infected trees is deterministic and probably inevitable. Our findings should inform scientists and managers throughout the world attempting to understand disease progression in regions recently invaded byP. ramorum(e.g. Europe) and/or affected by other exotic forest pathogens.
Fruit Removal and Natural Seed Dispersal of the Brazil Nut Tree (Bertholletia excelsa) in Central Amazonia, Brazil
Authors: Tuck Haugaasen Joanne M. , Haugaasen Torbjørn , Peres Carlos A. , Gribel Rogerio , Wegge Per 
Published: September 2011

ABSTRACTExperimental approaches to study seed dispersal of the Brazil nut tree have hitherto relied on exposed seeds deposited on the forest floor. Here we use a new method to study the natural dispersal by large rodents such as agoutis; tracking experimentally manipulated and tagged fruits containing individually marked seeds. Fruit manipulation did not deter agoutis from handling fruits. We found that agoutis usually moved intact fruits away from their original location below the parent tree before either hiding them or gnawing through the pericarp to access the seeds inside. Most fruits were moved to distances of 15–30 m from their original position, but some fruits could be taken as far as 60 m. A large number of seeds extracted from manipulated fruits appeared to be eaten immediately. Only 27 out of 1740 experimental seeds were found buried in shallow caches, generally within 5 m of the opened fruit. Fruit removal distance accounted for a disproportionate amount of total seed movement and seeds in the current study were dispersed significantly farther than in a previous experiment using exposed seeds, suggesting that classic dispersal experiments of this character may severely underestimate seed dispersal distances. We therefore conclude that the new method provides a more realistic and accurate approach to investigate natural seed dispersal of Brazil nuts and that the removal of fruits from underneath parent trees before being opened is the key to the significantly increased distances at which seeds are dispersed.Abstract in Portuguese is available at http://www.blackwell‐synergy.com/loi/btp.
Debris disc candidates in systems with transiting planets
Authors: Krivov A. V. , Reidemeister M. , Fiedler S. , Löhne T. , Neuhäuser R. 
Published: September 2011

ABSTRACT
Debris discs are known to exist around many planet-host stars, but no debris dust has been found so far in systems with transiting planets. Using publicly available catalogues, we searched for infrared excesses in such systems. In the recently published Wide-field Infrared Survey Explorer catalogue, we found 52 stars with transiting planets. Two systems with one transiting ‘hot Jupiter’ each, TrES-2 and XO-5, exhibit small excesses both at 12 and at 22 μ m at a ≳3σ level. Provided that one or both of these detections are real, the frequency of warm excesses in systems with transiting planets of 2–4 per cent is comparable to that around solar-type stars probed at similar wavelengths with Spitzer’s MIPS and IRS instruments. Modelling suggests that the observed excesses would stem from dust rings with radii of several  au. The inferred amount of dust is close to the maximum expected theoretically from a collisional cascade in asteroid belt analogues. If confirmed, the presence of debris discs in systems with transiting planets may put important constraints on the scenario of formation and migration of hot Jupiters.
Inter‐specific and intra‐specific variability in fruit color preference in two species of Turdus
Authors: LARRINAGA Asier R. 
Published: September 2011

AbstractOne of the main hypotheses proposed to explain the evolution of fruit color deals with a preference of avian frugivores for specific colors, mainly black and red, which are the most common fruit colors in many of the studied habitats. I analyzed fruit color preferences by wild birds belonging to 2 species of the highly frugivorous genus Turdus (Eurasian Blackbird Turdus merula Linnaeus, 1758 and Redwing Turdus iliacus Linnaeus, 1758) by means of captivity experiments with artificial fruits. Despite important within‐individual (i.e. temporal) and among‐individual variability, consistent patterns of species‐specific color preferences emerged. Eurasian Blackbirds tended to prefer red over blue, green and black, whereas Redwings seemed to prefer black over the rest. Green was systematically avoided by both species, suggesting that it might signal unripeness of fruits. Both preferred colors have been previously reported as the most common among fleshy‐fruited plants. The high variability, both within and between individuals, in preferences suggests that they can be subject to changes through experience and learning and, therefore, are not likely to drive the evolution of fruit color. The main differences between both species could be related to the most common fruit color they fed upon during the last months before capture.
Corneal biomechanical properties in normal‐tension glaucoma
Authors: Morita Tetsuya , Shoji Nobuyuki , Kamiya Kazutaka , Fujimura Fusako , Shimizu Kimiya 
Published: September 2011

Abstract.Purpose:  To investigate the intraocular pressure (IOP) and corneal biomechanical properties of normal and normal‐tension glaucoma (NTG) eyes.Methods:  This study included 83 normal and 83 NTG eyes. We measured corneal‐compensated IOP (IOPcc), Goldmann‐correlated IOP (IOPg), corneal resistance factor (CRF), corneal hysteresis (CH) and central corneal thickness (CCT) three times each for normal and NTG eyes using an Ocular Response Analyzer (ORA).Results:  No significant difference in CCT was seen between normal eyes (541.4 ± 26.8 μm) and NTG eyes (535.4 ± 24.9 μm; p = 0.16). IOPcc was significantly higher in NTG eyes (16.1 ± 2.6 mmHg) than in normal eyes (15.1 ± 2.9 mmHg; p = 0.01), while IOPg was significantly lower in NTG eyes (14.1 ± 2.7 mmHg) than in normal eyes (15.1 ± 3.0 mmHg; p = 0.04). CRF and CH were significantly lower in NTG eyes (CRF, 8.9 ± 1.5 mmHg; CH, 9.2 ± 1.3 mmHg) than in normal eyes (CRF, 10.6 ± 1.4 mmHg; CH, 10.8 ± 1.3 mmHg; p < 0.0001 each).Conclusion:  IOPcc was significantly higher in NTG eyes than in normal eyes. The ORA may be useful for distinguishing between the IOPcc of NTG eyes with normal IOP and that of normal eyes. In addition, the ORA enables CRF and CH to be measured in vivo, and weakness of the lamina cribrosa may be clinically inferred from the fact that CRF and CH were reduced in NTG eyes in our study. Low CRF and CH may be clues to the pathology of NTG.
Visual loss after use of intraocular silicone oil associated with thinning of inner retinal layers
Authors: Christensen Ulrik C. , la Cour Morten 
Published: September 2011

Abstract.Purpose:  To investigate the incidence and cause of severe visual loss following use and removal of intraocular silicone oil (SiO) after uncomplicated vitrectomy and SiO injection for primary rhegmatogenous retinal detachment (RRD).Methods:   Consecutive case series of 216 patients operated with vitrectomy for primary RRD in 2004–2005. In 162 eyes, SiO (5500 centiStoke) had been used as intravitreal tamponade and in 54 eyes gas (perflouropropane, C3F8) had been used. Following chart review, we identified 16 eyes in 16 patients (nine SiO eyes, seven gas eyes) with macula‐on and documented visual acuity ≥6/12 before surgery, where SiO had been removed, cataract surgery performed and no re‐detachment had occurred. Examinations included best‐corrected visual acuity (BCVA) and high‐definition optical coherence tomography (OCT) of the macular area.Results:  Preoperative characteristics were identical between SiO and gas eyes. Postoperative BCVA was significantly worse in SiO eyes (>6/24) compared to gas eyes (>6/7.5), p = 0.005. Three of 9 (33%) SiO eyes had final BCVA ≤6/60 and 67% had final BCVA ≤6/12. No gas eyes had final BCVA <6/9. Macular OCT revealed thinning of inner retinal layers in SiO‐operated eyes (5148 pixels) compared to gas‐operated eyes (6897 pixels), p < 0.002. No other visually significant structural differences were found.Conclusion:  Severe visual loss after SiO use was observed in 1/3 of patients with otherwise good visual potential. The visual loss was associated with a significant reduction in inner retinal thickness indicating neuronal cell loss in the macular area as a possible explanation.
Preliminary investigations for the option to use fast uniform scanning with compensators on a gantry designed for IMPT
Authors: Zenklusen Silvan M. , Pedroni Eros , Meer David , Bula Christian , Safai Sairos 
Published: August 2011

Purpose:In this experimental study, the authors explored the possibility to deliver the dose for proton therapy with fast uniform scanning on a gantry primarily designed for the delivery of conformal beam scanning and IMPT. The uniform scanning submode has been realized without equipment modifications by using the same small pencil beam used for conformal scanning, resulting in reduced realization costs. Uniform scanning has recently been adopted in a few proton therapy centers, as a basic beam delivery solution, and as an alternative to the use of scattering foils. The option to use such a mode to mimic scattering on a full‐fledged scanning gantry could be of interest for treating some specific indications and as a possible solution for treating moving targets.Methods:Uniform iso‐energy dose layers were painted by fast magnetic scanning alternated with fast energy changes with the gantry beam line. The layers were stacked and repainted appropriately to produce homogeneous three‐dimensional dose distributions. A collimator/compensator was used to adjust the dose to coincide laterally/distally with the target volume. In addition, they applied volumetric repainting, since they are confident that this will further mitigate the effects of organ motion as compared with the presently used clinical scanning solutions. With the approach presented in this paper, they can profit from the higher flexibility of the scanning system to obtain additional advantages. For instance the shape of the energy layers can be adjusted to the projected target shape in order to reduce treatment time and neutrons produced in the collimator. The shape of the proximal layers can be shrunk, according to the cross section of the target at the corresponding range. This provides variable range modulation (proximal conformity) while standard scattering only provides fixed range modulation with unnecessary 100% dose proximal to the target. The field‐specific hardware for a spherical target volume was mounted on the Gantry 2 nozzle. One field with proximal field size shrinking and one without, each of 1 Gy, were delivered. The dose distributions at different depths were recorded as CCD images of a scintillating screen.Results:The time to scan the volume once was about 4 s and the total delivery time was approximately 30 s. For the field with proximal conformity, dose sparing of up to 25% was measured in the region proximal to the target. A repainting capability of 48 times was achieved on the most distal layer. The proximal layers were repainted more due to the contribution of the plateau dose from the deeper layers.Conclusions:The flexibility of a fast scanning gantry with very fast energy changes can easily provide beam delivery by uniform layer stacking with a significant degree of volumetric repainting and with the benefit of a dose reduction proximal to the target volume.