bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salt chamber treatment is ineffective in treating eosinophilic inflammation in asthma
Authors: Sandell J. , Hedman J. , Saarinen K. , Haahtela T. 
Published: November 2012

AbstractBackgroundWe have shown that salt chamber treatment reduces airway hyper‐responsiveness as an add‐on therapy in adult asthmatics on inhaled corticosteroids.MethodsWe assessed whether this effect is due to the suppression of eosinophilic airway inflammation. Thirty‐nine adult asthmatics on inhaled corticosteroids were randomized to receive active salt chamber treatment with low‐salt treatment 6.6 mg/m3 (n = 14), high‐salt treatment 10.8 mg/m3 (n = 15) or placebo 0.3 mg/m3 (n = 10) 10 times in a 2 weeks' period in a double‐blind manner.ResultsThe level of induced sputum eosinophilic cationic protein μg/l, was 3070 before and 4651 after the low‐salt treatment period, on average. In the high‐salt treatment group, it was 12 192 μg/l vs 11 803 and in the placebo group 3942 vs 4144, respectively. Salt chamber treatment had no effect on sputum eosinophil or neutrophil cell numbers.ConclusionsThe reduction in hyper‐responsiveness observed in the previous study is probably not due to the effect on eosinophilic inflammation.
Co‐expression of NaVβ subunits alters the kinetics of inhibition of voltage‐gated sodium channels by pore‐blocking μ‐conotoxins
Authors: Zhang Min‐Min , Wilson Michael J , Azam Layla , Gajewiak Joanna , Rivier Jean E , Bulaj Grzegorz , Olivera Baldomero M , Yoshikami Doju 
Published: November 2012

Background and PurposeVoltage‐gated sodium channels (VGSCs) are assembled from two classes of subunits, a pore‐bearing α‐subunit (NaV1) and one or two accessory β‐subunits (NaVβs). Neurons in mammals can express one or more of seven isoforms of NaV1 and one or more of four isoforms of NaVβ. The peptide μ‐conotoxins, like the guanidinium alkaloids tetrodotoxin (TTX) and saxitoxin (STX), inhibit VGSCs by blocking the pore in NaV1. Hitherto, the effects of NaVβ‐subunit co‐expression on the activity of these toxins have not been comprehensively assessed.Experimental ApproachFour μ‐conotoxins (μ‐TIIIA, μ‐PIIIA, μ‐SmIIIA and μ‐KIIIA), TTX and STX were tested against NaV1.1, 1.2, 1.6 or 1.7, each co‐expressed in Xenopus laevis oocytes with one of NaVβ1, β2, β3 or β4 and, for NaV1.7, binary combinations of thereof.Key ResultsCo‐expression of NaVβ‐subunits modifies the block by μ‐conotoxins: in general, NaVβ1 or β3 co‐expression tended to increase kon (in the most extreme instance by ninefold), whereas NaVβ2 or β4 co‐expression decreased kon (in the most extreme instance by 240‐fold). In contrast, the block by TTX and STX was only minimally, if at all, affected by NaVβ‐subunit co‐expression. Tests of NaVβ1 : β2 chimeras co‐expressed with NaV1.7 suggest that the extracellular portion of the NaVβ subunit is largely responsible for altering μ‐conotoxin kinetics.Conclusions and ImplicationsThese results are the first indication that NaVβ subunit co‐expression can markedly influence μ‐conotoxin binding and, by extension, the outer vestibule of the pore of VGSCs. μ‐Conotoxins could, in principle, be used to pharmacologically probe the NaVβ subunit composition of endogenously expressed VGSCs.
Biochemical and pharmacological characterization of AZD1981, an orally available selective DP2 antagonist in clinical development for asthma
Authors: Schmidt JA , Bell FM , Akam E , Marshall C , Dainty IA , Heinemann A , Dougall IG , Bonnert RV , Sargent CA 
Published: November 2012

Background and PurposeThe discovery of DP2 as a second receptor for PGD2 has prompted the search for antagonists as potential novel therapies based on the associations between PGD2 and disease. Here we describe the biochemical and pharmacological properties of 4‐(acetylamino)‐3‐[(4‐chlorophenyl)thio]‐2‐methyl‐1H‐indole‐1‐acetic acid (AZD1981), a novel DP2 receptor antagonist.Experimental ApproachBinding to DP2, functional receptor pharmacology and selectivity were studied in both human and animal systems.Key ResultsAZD1981 displaced radio‐labelled PGD2 from human recombinant DP2 with high potency (pIC50 = 8.4). Binding was reversible, non‐competitive and highly selective against a panel of more than 340 other enzymes and receptors, including DP1 (>1000‐fold selective). AZD1981 inhibited DP2‐mediated shape change and CD11b up‐regulation in human eosinophils, shape change in basophils and chemotaxis of human eosinophils and Th2 cells with similar potency. AZD1981 exhibited good cross‐species binding activity against mouse, rat, guinea pig, rabbit and dog DP2. Evaluation in mouse, rat or rabbit cell systems was not possible as they did not respond to DP2 agonists. Agonist responses were seen in guinea pig and dog, and AZD1981 blocked DP2‐mediated eosinophil shape change. Such responses were more robust in the guinea pig, where AZD1981 also blocked DP2‐dependent eosinophil emigration from bone marrow.Conclusions and ImplicationsAZD1981 is a DP2 antagonist that blocks functional responses in eosinophils, Th2 cells and basophils. It exhibited similar potency irrespective of the cell type, DP2 agonist or species used. This selective orally active agent is currently under clinical evaluation as a potential therapeutic agent in respiratory diseases including asthma.
Craniofacial and dental malformations in Costello syndrome: A detailed evaluation using multi‐detector row computed tomography
Authors: Takahashi Masashi , Ohashi Hirofumi 
Published: November 2012

Abstract Costello syndrome is a rare multiple congenital anomaly syndrome caused by heterozygous germline HRAS mutations, which is characterized by intellectual disability, growth retardation, distinctive facies, loose skin, cardiomyopathy and a preposition to malignancies. Although teeth abnormalities have been encountered in nearly two‐thirds of the patients in literature, the evaluation tended to be limited to the extent which can be obtained from physical examination. We investigated detailed craniofacial, oral and dental findings in four patients with Costello syndrome. In this study, images reconstructed by multi‐detector row computed tomography (MDCT) were used as substitutes for dental cast study and panoramic and lateral cephalometric radiograph studies to evaluate dental arches, tooth size, relationships between craniofacial and dental structures, and hypodontia. All four patients showed true/relative macrocephaly with facial bone hypoplasia and gingival hypertrophy. Occlusal attrition, malocclusion, small dental arches, microdontia, and convex face were noted in three patients. In addition, one patient showed dental caries, conic tooth and gingivitis, and another patient showed hypodontia. Our study suggests that craniofacial and dental abnormalities are common in Costello syndrome patients and comprehensive dental care should be provided from early infancy. To our knowledge, this is the first study of thorough craniofacial and dental evaluation by using MDCT in Costello syndrome. MDCT is a useful tool for precise evaluation of craniofacial and oral manifestations in patients with congenital anomaly/intellectual disability syndromes.
Digoxin‐associated decrease in parathyroid hormone (PTH) concentrations in patients with atrial fibrillation
Authors: Apel Arie , Rachel Pauzner , Cohen Ohad , Mayan Haim 
Published: November 2012

AbstractBackgroundParathyroid hormone (PTH) secretion is regulated mainly by the calcium sensor receptor. Recently, other components of calcium homoeostasis have been revealed, namely the effect of Klotho on stimulation of PTH secretion by the recruitment of Na‐K‐ATPase and by its being a cofactor in the inhibitory effect of FGF 23 on PTH secretion. It seems that ouabain, a Na‐K‐ATPase inhibitor, prevents the increase in PTH secretion in a hypocalcemic environment, as observed in mouse and bovine tissues. We hypothesized that digoxin, which is similar to ouabain in its effect on the sodium pump, might decrease PTH levels in humans.MethodsTwenty patients with atrial fibrillation were studied. Ten patients were treated with digoxin and the other ten patients with verapamil. Baseline chemistry parameters were determined and 0·25 mg digoxin injected. Plasma PTH concentrations, ionized calcium concentrations and digoxin levels were recorded at 30 min, 1 h, 2 h and 4 h postinjection.ResultsBaseline blood parameters were similar in both groups. In the control group plasma PTH concentrations increased, whereas in the digoxin group, they decreased. Ionized calcium concentrations did not change over time in either groups. There seemed to be blunting of the circadian rhythm of PTH levels in the morning hours.ConclusionsAlthough the patients were normocalcemic, plasma PTH concentrations decreased with digoxin treatment. The effect of the sodium pump on PTH secretion might be important in human PTH homoeostasis and might be a potential target for the treatment of disturbances in calcium homoeostasis.
Pilot study of topical acetyl hexapeptide‐8 in the treatment for blepharospasm in patients receiving botulinum toxin therapy
Authors: Lungu C. , Considine E. , Zahir S. , Ponsati B. , Arrastia S. , Hallett M. 
Published: November 2012

Background and purposeInjectable botulinum neurotoxin (BoNT) is the principal effective treatment for blepharospasm (BSP). This trial explores the safety and efficacy of topical acetyl hexapeptide‐8 (AH8), a competitive SNAP25 inhibitor, as a potential new therapy in BSP.MethodsDouble‐blind, placebo‐controlled, randomized trial of daily topical application of AH8 in 24 patients with BSP. The primary outcome was time to return to baseline Jankovic Blepharospasm Rating Scale (JBRS) after a BoNT injection simultaneously with the initiation of AH8. Patients displaying a strictly regular pattern of response to 3‐monthly injections of BoNT were included.ResultsThere were no significant adverse events. There was a trend for longer time until return to baseline JBRS after injection in the active group compared to placebo (3.7 months vs. 3.0 months), and for better scores in the active group. One‐third (4/12) of the patients in the active group had a considerable extension of symptom control after BoNT (range: 3.3–7.1 months).ConclusionsTopical AH8 is safe and promising for extending the duration of action of BoNT therapy for BSP.
Occurrence of CCSVI in patients with MS and its relationship with iron metabolism and varicose veins
Authors: Van den Berg P. J. , Van den Berg G. B. , Westerhuis L. W. , Visser L. H. 
Published: November 2012

Background and purposeA new treatable venous disorder, chronic cerebrospinal venous insufficiency (CCSVI), has been proposed in patients with multiple sclerosis (MS). Its relationship with iron metabolism is suggested, but has not been examined prospectively.MethodsWe performed extra‐ and transcranial echo colour Doppler (ECD) in 90 patients with MS and 41 healthy controls (HC). Indices of iron metabolism and the presence of peripheral signs of impaired venous flow were also examined.ResultsThe ECD examination showed CCSVI in 8 (9%) of the 90 patients with MS and 0 HC (P = 0.11). The 8 CCSVI‐positive MS patients were older (P = 0.02), had less often relapsing–remitting‐MS (P = 0.02) and had more neurological disability assessed by expanded disability status scale (EDSS, P = 0.001) and longer duration of disease (P = 0.02) in comparison with the 82 CCSVI‐negative MS patients. Multivariate analysis revealed that EDSS remained an independent factor associated with CCSVI (odds ratio 1.89, 95%CI 1.17–3.05, P‐value = 0.009). CCSVI MS patients more often had bilateral telangiectasia at the legs (P = 0.008), reticular veins (P = 0.006) and venous stasis dermatitis (P = 0.004). No relationship was found between CCSVI and impaired iron metabolism in patients with MS.ConclusionsCCSVI is uncommon and is a secondary epiphenomenon in MS and related to more neurological disability and the presence of varicose veins at the legs.
Acclimation responses to temperature vary with vertical stratification: implications for vulnerability of soil‐dwelling species to extreme temperature events
Authors: van Dooremalen Coby , Berg Matty P. , Ellers Jacintha 
Published: November 2012

AbstractThe occurrence of summer heat waves is predicted to increase in amplitude and frequency in the near future, but the consequences of such extreme events are largely unknown, especially for belowground organisms. Soil organisms usually exhibit strong vertical stratification, resulting in more frequent exposure to extreme temperatures for surface‐dwelling species than for soil‐dwelling species. Therefore soil‐dwelling species are expected to have poor acclimation responses to cope with temperature changes. We used five species of surface‐dwelling and four species of soil‐dwellingCollembola that habituate different depths in the soil. We tested for differences in tolerance to extreme temperatures after acclimation to warm and cold conditions. We also tested for differences in acclimation of the underlying physiology by looking at changes in membrane lipid composition. Chill coma recovery time, heat knockdown time and fatty acid profiles were determined after 1 week of acclimation to either 5 or 20 °C. Our results showed that surface‐dwellingCollembola better maintained increased heat tolerance across acclimation temperatures, but no such response was found for cold tolerance. Concordantly, four of the five surface‐dwellingCollembola showed up to fourfold changes in relative abundance of fatty acids after 1 week of acclimation, whereas none of the soil‐dwelling species showed a significant adjustment in fatty acid composition. Strong physiological responses to temperature fluctuations may have become redundant in soil‐dwelling species due to the relative thermal stability of their subterranean habitat. Based on the results of the four species studied, we expect that unless soil‐dwelling species can temporarily retreat to avoid extreme temperatures, the predicted increase in heat waves under climatic change renders these soil‐dwelling species more vulnerable to extinction than species with better physiological capabilities. Being able to act under a larger thermal range is probably costly and could reduce maximum performance at the optimal temperature.
Poultry rearing and slaughtering practices in rural Egypt: an exploration of risk factors for H5N1 virus human transmission
Authors: Lohiniva Anna‐Leena , Dueger Erica , Talaat Maha , Refaey Samir , Zaki Amal , Chisholm Horton Katherine , Kandeel Amr 
Published: November 2012

Please cite this paper as: Lohiniva et al. (2012) Poultry rearing and slaughtering practices in rural Egypt: an exploration of risk factors for H5N1 virus human transmission. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12023.Background  Highly pathogenic avian influenza (H5N1) virus continues to cause infections in Egypt. This study describes the practices associated with raising and slaughtering household poultry to identify risk factors for H5N1 infection and reasons for non‐compliance with preventive measures.Methods  An investigation was conducted of 56 households with household flocks (19 households with human H5N1 cases, 19 with poultry H5N1 cases, and 18 with no reported poultry or human H5N1 cases). Data were collected via structured observations and in‐depth interviews.Results  Half of the households kept at least some free‐range poultry and mixed at least some different species of poultry as it was considered beneficial for the poultry. Feeding and cleaning practices exposed children to contact with poultry; slaughtering contaminated homes; use of personal protective barriers was not a norm; waste management exposed the communities to slaughtering waste and dead chickens; and reporting of sick and dead poultry was not a practice. Only minor changes in poultry‐handling took place following H5N1 virus outbreaks.Discussion  H5N1 virus prevention in Egypt represents both an epidemiological and socio‐cultural challenge. Traditional poultry‐rearing practices that likely increase exposures to H5N1‐infected poultry are common throughout Egypt. Despite education campaigns following sporadic H5N1 outbreaks, no differences in these practices could be detected between households with previous H5N1 human or poultry cases and those households with any previous experience with H5N1. Development of H5N1 infection–related education campaign strategies should focus on perceptions underlying traditional practices in order to tailor public awareness messages that are meaningful for communities.
The role of patient safety culture in the causation of unintended events in hospitals
Authors: Smits Marleen , Wagner Cordula , Spreeuwenberg Peter , Timmermans Danielle RM , van der Wal Gerrit , Groenewegen Peter P 
Published: November 2012

Aims and objectives.  To examine whether the relationship between specialty and patient safety is mediated by safety culture.Background.  Research has shown that patient safety in hospitals varies by specialty. The safety culture among healthcare professionals in hospital units is believed to influence safety performance. If there is a mediation effect of safety culture in the relationship between specialty and safety, then safety culture could explain why units vary in performance.Design.  Cross‐sectional observational study in 28 units of 20 hospitals in the Netherlands. Units were of three specialties: emergency medicine, surgery and internal medicine.Methods.  Safety culture was measured with the Dutch version of the Hospital Survey on Patient Safety Culture with 11 culture dimensions (n = 542; response 56%). Safety outcomes were types of unintended events (six types). Unintended events were collected through staff reporting (n = 1885 events). Data were examined using multilevel regression analysis.Results.  The overall safety culture in the units did not mediate the relationship between specialty and the safety outcomes (event types), but three of the 11 dimensions showed significant mediation on one or more event types: non‐punitive response to error, hospital management support and willingness to report.Conclusions.  Only a few safety culture dimensions mediated the relationship between specialty and some of the outcomes, with ‘willingness to report’ as the most important mediating factor. Our study did not give strong evidence that specialties differ in performance because of their safety cultures. More research into the causes of variation in patient safety between hospital units is needed.Relevance to clinical practice.  Our study could not give support for the claim that safety culture is a key factor affecting patient safety.
Bilateral prediction and intersection calculation autofocus method for automated microscopy
Authors: WU Z.M. , WANG D.H. , ZHOU F. 
Published: November 2012

SummaryIn this paper, a bilateral prediction and intersection calculation autofocus method for automated microscopy, which obtains the in‐focus position by calculating the intersection of the predicted left and right focus measure curves located respectively in the left and right sides of the peak position of the focus measure curve, is proposed and performed. According to the autofocus method, the area including the peak position of the focus measure curve and its left and right neighbourhoods should be determined firstly, and the left and right neighbourhoods are considered as the left and right sampling areas. The left and right focus measure curves are predicted by appropriate predicting models according to the two sample sequences, which comprise the focus values by evaluating the sampled images in the left sampling area and right sampling area, respectively and their corresponding sampling positions. The intersection of the predicted left and right focus measure curves is calculated and can be considered as the in‐focus position. The autofocus can be realized by moving the focus plane of the microscope to the intersection of the predicted left and right focus measure curves. The proposed bilateral prediction and intersection calculation autofocus method is experimentally verified in an automated light microscopy for implementing microassembly and micromanipulation. The theoretical analyses have shown that the proposed bilateral prediction and intersection calculation autofocus method can not only effectively avoid the principle error caused by assuming the symmetrical focus measure curve in the autofocus methods based on curve fitting, but also eliminate the possible waver search near the peak position in the modified fast climbing servo method. The experimental results have shown that the proposed bilateral prediction and intersection calculation autofocus method possesses the merits as follows: (1) the focusing accuracy is high and slightly affected by the sampling step size and (2) the focusing speed is higher than those of the 7‐point hill‐climbing search method and the quadratic curve fitting method with a determinate focusing accuracy.
Landscape of ecological research in Australia: A bibliometric analysis of trends in research output and hotspots of research from 1991 to 2010
Authors: KUMAR LALIT , KHORMI HASSAN M. 
Published: November 2012

AbstractThe spatial distribution and density of scientists can have important implications for key aspects of scientific processes, such as innovation, networking, rates of knowledge exchange and success in large competitive grants. In this paper, we examine the research output of different research organizations and universities in Australia, with the aim of identifying hotspots of ecological research and how these hotspots have changed over the last 20 years. We used publications from 10 reputable peer‐reviewed international journals as a measure of research output. We identified a number of ecology hotspot clusters. Some clusters have developed significantly over the last 20 years, while others have declined in output over time. The University of Sydney, University of Queensland, James Cook University and Melbourne University had the largest output levels among universities. Results also showed large increases in output over the last 5‐year period (2006–2010), possibly because of the impending introduction of the Excellence in Research for Australia.
Review: efficacy of alginate supplementation in relation to appetite regulation and metabolic risk factors: evidence from animal and human studies
Authors: Georg Jensen M. , Pedersen C. , Kristensen M. , Frost G. , Astrup A. 
Published: November 2012

SummaryThis review provides a critical update on human and animal studies investigating the effect of alginate supplementation on appetite regulation, glycaemic and insulinemic responses, and lipid metabolism with discussion of the evidence on potential mechanisms, efficacy and tolerability. Dependent on vehicle applied for alginate supplementation, the majority of animal and human studies suggest that alginate consumption does suppress satiety and to some extent energy intake. Only one long‐term intervention trial found effects on weight loss. In addition, alginates seem to exhibit beneficial influence on postprandial glucose absorption and insulin response in animals and humans. However, alginate supplementation was only found to have cholesterol‐lowering properties in animals. Several mechanisms have been suggested for the positive effect observed, which involve delayed gastric emptying, increased viscosity of digesta and slowed nutrient absorption in the small intestine upon alginate gel formation. Despite reasonable efficacy and tolerability from the acute or short‐term studies, we still realize there is a critical need for development of optimal alginate types and vehicles as well as studies on further long‐term investigation on alginate supplementation in humans before inferring that it could be useful in the management of obesity and the metabolic syndrome.