bluuebunny/crossref_metadata_2025 huggingface dataset:
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 Purpose

Voltage‐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 Approach

Four 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 Results

Co‐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 Implications

These 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 Purpose

The 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 Approach

Binding to DP2, functional receptor pharmacology and selectivity were studied in both human and animal systems.

Key Results

AZD1981 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 Implications

AZD1981 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

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

Background

Parathyroid 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.

Methods

Twenty 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.

Results

Baseline 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.

Conclusions

Although 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 purpose

Injectable 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.

Methods

Double‐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.

Results

There 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).

Conclusions

Topical 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 purpose

A 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.

Methods

We 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.

Results

The 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.

Conclusions

CCSVI 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

The 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

In 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

The 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

This 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.
Towards a Grammatical Analysis of Scelsi's Late Music
Authors: Dickson Ian
Published: November 2012

Giacinto Scelsi (1905–1988) is a problematic figure for musical analysis on account of his extreme anti‐rationalism and devaluing of the score. By the 1950s he was creating music through improvisation and delegating to assistants the task of transcribing the results. The idiom he evolved was novel not only in its extreme economy of means, usually consisting of subtle inflections of continuous sounds, but also in its apparent rejection of any rational organisation.

Analysts of Scelsi's work have tended to concentrate on large‐scale musical architecture, neglecting the apparently redundant, non‐developmental gestures from which, nonetheless, this architecture must be built up. Many of Scelsi's advocates have encouraged this by insisting on the music's irreducibility and exceptional rapport with sound. Such an argument stems from the composer's own mysticism: he attributed the automaticity of his improvisations to the cosmic power of sound, rather than to the long hours that he spent creating them.

This article explores the idea that Scelsi's music is conditioned, if not by an explicit grammar (traditional or avant‐garde), then by the ‘model’ of the original improvisations, and that his manipulation of nuance can be considered as a kind of syntax. It argues that a grammatical analysis accounts for the persuasiveness and variety of the improvisations more plausibly than statistical analysis or metaphysical formulations involving sound ‘itself’.
Surface salinity and nutrient variations during the Littorina Stage in the Fårö Deep, Baltic Sea
Authors: Willumsen PI Suhr , Filipsson Helena L. , Reinholdsson Maja , Lenz Conny
Published: November 2012

Early to late Holocene sediments from core F80, Fårö Deep, Baltic Sea, are investigated for their palynomorph composition and dinoflagellate cyst record to map variations in sea‐surface‐water salinity and palaeoproductivity during the past 6000 years. The F80 palynomorph assemblages are subdivided into four Assemblage Zones (AZs) named A to D. The transition from the stratigraphically oldest AZ A to B reflects a marked increase in palaeoproductivity and a gradual increase in surface‐water salinity over the ∼1500 years between the Initial Littorina (former Mastogloia Sea Stage) and Littorina Sea Stage. A period with maximum sea‐surface salinity is recorded within the overlying AZ C from 7200 to 5200 cal. a BP, where the process length of Operculodinium centrocarpum indicates that average salinities were probably the highest (∼15–17 versus 7.5 psu today) since the last glaciation. The change from AZ C to D correlates with a shift from laminated to non‐laminated sediments, and the dinoflagellate cyst assemblages suggest that the surface‐ and the deep‐water environment altered from c. 5250 cal. a BP, with less productivity in the surface water and more oxygenated conditions in the deep water. Here we demonstrate that past regional changes in surface salinity, primary productivity and deep‐water oxygenation status in the Baltic Sea can be traced by mapping overall palynomorph composition, dinoflagellate cyst assemblages and variations in the process length of O. centrocarpum in relation to periods of laminated/non‐laminated sedimentation and proportion of organic‐matter in the sediments. An understanding of past productivity changes is particularly important to better understand present‐day environmental changes within the Baltic Sea region.
Dating of snow avalanches by means of wound‐induced vessel anomalies in sub‐arctic Betula pubescens
Authors: Arbellay Estelle , Stoffel Markus , Decaulne Armelle
Published: November 2012

Dendrogeomorphic research has long relied on scarred trees to reconstruct the frequency of mass‐movement processes. Injuries have mostly been dated macroscopically by counting the tree rings formed after wounding. Tree‐ring anatomical anomalies induced by cambial injury, in contrast, have only recently been recognized as proxy records of past events. We investigated 12 sub‐arctic downy birch (Betula pubescens Ehrh.) trees scarred by snow avalanches in Norway and Iceland. Earlywood vessel lumina were measured for each tree in the xylem tissue bordering the scars. Seven successive rings were examined, namely two control rings laid down prior to wounding and five rings in the wound xylem. We provide evidence that snow‐avalanche‐induced wounding resulted in atypically narrow earlywood vessels over at least two years. Our data demonstrate that wound‐associated vessel anomalies represent tangible markers of mass‐movement processes, and as such make a viable tool for reconstructing past events. Similar dendrogeomorphic studies based on tree‐ring anatomy can be readily conducted with other mass‐movement processes, as well as with other broad‐leaved tree species. Ultimately, this new approach will foster increment coring over more invasive sampling techniques.
Bisphenol A in Chronic Kidney Disease
Authors: Krieter Detlef H. , Canaud Bernard , Lemke Horst‐Dieter , Rodriguez Annie , Morgenroth Andreas , von Appen Kai , Dragoun Gerd‐Peter , Wanner Christoph
Published: November 2012

The estrogenic endocrine‐disrupting substance bisphenol A (BPA) is extensively used as a starting material for a variety of consumer plastic products including dialyzer materials. The present study was performed to explore plasma BPA levels in patients with impaired renal function and to investigate if dialyzers differing in elutable BPA influence plasma levels in patients on maintenance hemodialysis. In vitro BPA was eluted from high‐flux polyethersulfone (PUREMA H, referred as PUR‐H), high‐flux polysulfone (referred as HF‐PSu), and low‐flux polysulfone (referred as LF‐PSu) dialyzers by recirculation with water for 180 min. In a cross‐sectional clinical study, plasma BPA levels of outpatients with different stages of chronic kidney disease (CKD) from four different centers were determined. Furthermore, in a prospective, randomized, and crossover setting, 18 maintenance dialysis patients were subjected successively to 4 weeks of thrice‐weekly hemodialysis with each LF‐PSu, HF‐PSu, and PUR‐H. In addition, the fractions of protein‐bound and free BPA were determined in a subset of dialysis patients. The mass of BPA eluted from the blood compartments in vitro under aqueous conditions varied for the three dialyzers being very low for PUR‐H (6.2 ± 2.5 ng; P < 0.001), intermediate for HF‐PSu (48.1 ± 7.7 ng), and highest for LF‐PSu (140.8 ± 38.7 ng; P < 0.01). In 152 prevalent patients with CKD enrolled in the cross‐sectional trial, plasma BPA started to rise after stage 3. Maintenance hemodialysis patients had more than six times higher BPA concentrations than patients with CKD stage 5 not yet on dialysis (10.0 ± 6.6 vs. 1.6 ± 1.8 ng/mL; P < 0.001). The BPA concentrations highly and inversely correlated with renal function. In the randomized controlled study, the plasma BPA concentrations were highly elevated compared with healthy controls (range 9.1 ± 4.5–12.0 ± 6.0 ng/mL vs. ≤0.2 ± 0.1 ng/mL; P < 0.001), but no change of the plasma levels was observed during hemodialysis with any of the three dialyzers in the course of a single treatment and over a period of 4 weeks. The protein‐bound fraction of plasma BPA in the dialysis patients was 74 ± 5%. Renal function and, most likely, the total quantity of ingested BPA are essential parameters affecting plasma BPA concentrations. Dialyzers are one additional source of BPA, but differences in the elutable BPA content are not associated with a significant effect on BPA plasma levels in Western European maintenance dialysis patients. Due to high protein binding, the removal of BPA by hemodialysis is limited.
Consumption of beef/veal/lamb in Australian children: Intake, nutrient contribution and comparison with other meat, poultry and fish categories
Authors: Bowen Jane , Baird Danielle , Syrette Julie , Noakes Manny , Baghurst Katrine
Published: November 2012

Aim

To describe reported consumption of meat for children using the 2007 Australian National Children's Nutrition and Physical Activity Survey.

Methods

One‐day, weighted data are described for consumption of meat, poultry and fish consumed as ‘cuts’ and from mixed dishes. Data are presented for all children by age groups (2–3 years, 4–8 years, 9–13years, 14–16 years) and gender. Trimming practices, time and place of consumption, and nutrient contributions are described.

Results

Ninety per cent of children reported consuming meat, poultry or fish on the day surveyed. Reported mean consumption of all beef/veal/lamb, pork/ham/bacon, poultry and fish ranged from 52 g in 2 to 3‐year‐old boys to 161 g in 14 to 16‐year‐old boys; and was lower in 9 to 16‐year‐olds girls; 98 g.

Mean reported consumption of beef/veal/lamb was 21–64 g for boys and 23–36 g for girls, depending on age group.

For meals where the meat, poultry or fish were identified individually, meals with beef/veal/lamb contained more vegetables (159 g) than pork/ham/bacon (50 g) and poultry (110 g). The beef/veal/lamb was fully (20%) or semi‐trimmed (58%), and 49% of minced beef/veal/lamb was lean. Sixty‐eight per cent of respondents reported eating poultry with the skin removed.

Across all age groups, beef/veal/lamb in cuts and mixed dishes contributed 4% of total energy, 6% of total fat, 5% of saturated fat, 46% of haem iron, 18% of zinc and 21% of long‐chain omega‐3 fatty acid intake.

Conclusions

These findings help to inform evidence‐based individual or population‐level recommendations.
Long bone fracture as a complication following external skeletal fixation: 11 cases
Authors: Knudsen C. S. , Arthurs G. I. , Hayes G. M. , Langley‐Hobbs S. J.
Published: November 2012

OBJECTIVES

To report on a series of dogs and cats with long bone fractures that occurred as a direct consequence of linear external skeletal fixation (ESF) application.

METHODS

Retrospective study. Data from the medical records and radiographs of canine (n = 4) and feline (n = 7) cases were collected from three referral and three first opinion practices in theUK(1999 to 2011).

RESULTS

Long bone fractures occurred following the application of linearESFeither while theESFwas in situ or after removal. All fractures occurred through either a pin tract or an empty drill hole. Pins associated withESF‐related fracture tended to be in the higher end of the recommended size range. The majority of cases had additional complicating factors such as multiple injuries, revision surgery, poor owner compliance with postoperative exercise restriction and the presence of empty drill holes.

CLINICAL SIGNIFICANCE

In cases with features that could complicate outcome, careful attention should be paid to recommendations forESFapplication. Leaving empty drill holes is suboptimal. The retrospective nature of the study, low numbers of, and diversity amongst, cases should be taken into consideration when interpreting the results from this study.
Using endemism to assess representation of protected areas – the family Myrtaceae in the Greater Blue Mountains World Heritage Area
Authors: Laffan Shawn W. , Ramp Daniel , Roger Erin
Published: November 2012

Aim

We assess how much of species' ranges are present within protected areas and how different land units within protected areas contribute to overall protection, both within their region and at continental scales. We do this using the plant family Myrtaceae in relation to the globally important Greater Blue Mountains World Heritage Area (GBMWHA) in New South Wales, Australia.

Location

South‐eastern Australia.

Methods

Compiling data throughout the region and nationally, we considered two spatially based quantitative measures of endemism (relative range restriction): weighted endemism (WE) and corrected weighted endemism (CWE). In both measures, species are weighted by the proportion of their ranges found within the analysis window, with the ranges calculated as the total number of cells in which they occur (10 km × 10 km in this research). We also derived a novel expectation for the contribution of each species to the endemism scores at each taxonomic level based on the additive properties of the metrics and their relationship to species richness. We used this expectation to assess the proportional contribution of each genus to the endemism scores.

Results

The degree to which Myrtaceae species within the GBMWHA are endemic to the GBMWHA area is 16%, meaning that an average of 16% of the ranges of species found in the GBMWHA are restricted to that area. The figure for those species with ranges less than or equal to the median (80 cells) is 33%. The genus Eucalyptus contributes the most to the endemism scores obtained, but no more than would be expected given its number of species. The genus Leptospermum is 3.7% less restricted to the GBMWHA than would be expected, while the genus Melaleuca is 5% more restricted than expected.

Main conclusions

Centres of high endemism within the GBMWHA and surrounds were identified. This research presents a template for quantifying endemism for regions at local to global scales. Spatially‐based quantitative measures of endemism, such as outlined here, are an important means to quantify and visualize these aspects of conservation significance for the management of protected areas.
Peripheral Adrenoceptors: The Impetus Behind Glucose Dysregulation and Insulin Resistance
Authors: Boyda H. N. , Procyshyn R. M. , Pang C. C. Y. , Barr A. M.
Published: November 2012

It is now accepted that several pharmacological drug treatments trigger clinical manifestations of glucose dysregulation, such as hyperglycaemia, glucose intolerance and insulin resistance, in part through poorly understood mechanisms. Persistent sympathoadrenal activation is linked to glucose dysregulation and insulin resistance, both of which significantly increase the risk of emergent endocrinological disorders, including metabolic syndrome and type 2 diabetes mellitus. Through the use of targeted mutagenesis and pharmacological methods, preclinical and clinical research has confirmed physiological glucoregulatory roles for several peripheral α‐ and β‐adrenoceptor subtypes. Adrenoceptor isoforms in the pancreas (α2A and β2), skeletal muscle (α1A and β2), liver (α1A & B and β2) and adipose tissue (α1A and β1 & 3) are convincing aetiological targets that account for both immediate and long‐lasting alterations in blood glucose homeostasis. Because significant overlap exists between the therapeutic applications of numerous classes of drugs and their associated adverse side‐effects, a better understanding of peripheral adrenoceptor‐mediated glucose metabolism is thus warranted. Therefore, at the same time as providing a brief review of glucose homeostasis in the periphery, the present review addresses both functional and pathophysiological roles of the mammalian α1, α2, and β‐adrenoceptor isoforms in whole‐body glucose turnover. We highlight evidence relating to the clinical use of common adrenergic drugs and their impacts on glucose metabolism.
Properties and Nematicide Performance of Avermectins
Authors: Cabrera Jose Alfonso , Menjivar Roy D. , Dababat Abd el‐Fattah A. , Sikora Richard A.
Published: November 2012

In 1979, the anthelmintic activity of abamectin, a mixture of avermectins B1a and B1b, was first reported. Since then, multiple articles have investigated avermectins' degradation and its efficacy against a wide variety of pests under different conditions and using different modes of application. However, there is a gap in the literature of analysing abamectin properties and its performance as a non‐fumigant nematicide when applied liquid or granular vs. new avenues of application based on seed and seedling treatment. Therefore, this article reviewed literature to discuss the mode of action, environmental aspects, the nematicidal effectiveness of treatment forms and the range of activity to address these topics.
Assessing the community clinic replacement effect on private Medicaid practices in oral health care within rural environments
Authors: Squillace Joe
Published: November 2012

Objectives

Children in Medicaid/CHIP public coverage programs who reside in rural counties have limited access to dental care services. Shortages of dental professionals in rural areas impede utilization of dental care. Public and private initiatives are attempting to address this crisis. Missourians instituted deregulatory policies and invested in community‐based initiatives.

Methods

Using a Medicaid/CHIP claims administrative dataset from 2004 to 2007, this research explored patterns of utilization to assess the impact of these efforts.

Results

The number of participating private dental office providers declined over the study period, and the number of children utilizing clinics increased. Trends are being observed within the public health dental care market demonstrating clinics are replacing private dentists as providers of Medicaid/CHIP dental services.

Conclusions

Allowing greater market entry through deregulation could provide states with greater improvements to their public dental health infrastructure.
Prisons: the psychiatric institution of last resort?
Authors: Huxter M. J.
Published: November 2012

Accessible summary

Throughout recorded history, the mentally ill have been living at the fringes of society, frequently alienated, treated inhumanely, and made as scapegoats for the prevailing societal ills.

Australia has seen the number of public psychiatric hospital beds fall from 30 000 in the early 1960's to 8000 as of 2006. The Australian population has more than doubled since this time, such phenomena is mirrored in the UK and the USA.

As of June 2011, there were 28 964 individuals detained in Australian prisons, this represents a figure close to 70% higher than in comparison to the figure reported in 1996. However, Australia's population has only increased by just over 27% in this time period.

Authors and researchers are claiming that a debilitated public psychiatric healthcare system has resulted in large ‘trans‐migrations’ of patients from psychiatric hospital beds to prisons and jails, via an intermediary period in their communities.

The World Health Organization declared in 1948 that the enjoyment of the highest individual attainment of health for any person is a fundamental human right. Australia, the UK and the United States all legally ratified this declaration as becoming signatories to their founding treatise with the United Nations. Despite this, there are many conspicuous examples of inequities of public health as found within these nations. One of the more disparate and outrageous examples of inequities in public health has been an insidious trend towards criminalizing mental illness, and the largely unjust treatment of many mentally ill persons. This change has resulted in untold numbers of mentally ill persons being over‐represented within the criminal justice system, experiencing higher morbidity, co‐morbidity and mortality rates, and having difficulty in surviving in a society frequently dealing with their illness in a persecutory manner. Questions must be raised: that although over the passage of time medical science and technology has changed, but has western societies’ attitudes to health equity kept pace?
The experience of weight gain as a result of taking second‐generation antipsychotic medications: the mental health consumer perspective
Authors: Usher K. , Park T. , Foster K.
Published: November 2012

Accessible summary

Weight gain is a known, predictable side‐effect of second‐generation antipsychotic drugs.

Study participants reported struggling to manage the insatiable appetite and weight gained associated with the drugs.

Cessation of prescribed medication was considered by most as a way of managing the weight gain associated with the drugs.

This interpretive qualitative study aimed to describe and construct the meaning of the experience of living with the weight gain associated with second‐generation antipsychotics. A qualitative study that incorporated the tenets of phenomenology and utilized in‐depth interviews was conducted with eight mental health consumers. Thematic analysis resulted in three themes: Grappling with the weight; Living with the consequences of being overweight; and Experiencing negative emotions about the weight gain. The findings indicate that consumers struggle to manage the insatiable appetite and the related weight gain associated with second‐generation antipsychotic medication, as well as the numerous associated physical and emotional issues. Adherence with prescribed second‐generation antipsychotic medication was also affected and a number of the participants indicated they had ceased or considered ceasing their medication because of the weight gain associated with the drugs.
Increased renal expression and urinary excretion of TLR4 in acute kidney injury associated with cirrhosis
Authors: Shah Naina , Mohamed Fatma E. , Jover‐Cobos Maria , Macnaughtan Jane , Davies Nathan , Moreau Richard , Paradis Valerie , Moore Kevin , Mookerjee Raj , Jalan Rajiv
Published: November 2012

Background

Patients with cirrhosis frequently develop renal dysfunction, a proportion of who do not fulfill criteria for hepatorenal syndrome (HRS). We hypothesized that the kidneys in these patients would exhibit histological and biomarker evidence of kidney injury. We looked specifically for TLR expression as they may mediate kidney injury.

Methods

Sixty seven subjects (6); alcoholic cirrhosis: compensated (9), acute deterioration of alcoholic cirrhosis (52)] were included. Renal dysfunction was defined as a creatinine of >133 μmol/L and/or according to the AKI network criteria. Urinary biomarkers, KIM‐1, πGST, αGST and a novel biomarker, urinary TLR4 were measured. Renal biopsies were also available from eight other alcoholic cirrhosis patients (three non‐HRS renal dysfunction; five HRS) that were stained for TLR4 and caspase‐3.

Results

Fourteen patients developed renal dysfunction, amongst these three had type 2 HRS. KIM‐1, πGST and αGST were higher in patients with acute deterioration of cirrhosis compared with patients with compensated cirrhosis, but did not differ between those with and without renal dysfunction. Urinary TLR4 was significantly higher in patients with renal dysfunction associated with infection/inflammation. Kidney biopsies from non‐HRS renal dysfunction patients showed tubular damage with evidence of increased tubular expression of TLR4, and caspase‐3. Minor changes were observed in HRS patients.

Conclusions

The data provide proof of concept that renal dysfunction in patients with cirrhosis with superimposed inflammation is associated with significant tubular injury and apoptosis and with increased renal expression and urinary excretion of the TLR4, suggesting a potential role of TLR4 as mediator of renal injury.
Increased expression of mitochondrial proteins associated with autophagy in biliary epithelial lesions in primary biliary cirrhosis
Authors: Sasaki Motoko , Miyakoshi Masami , Sato Yasunori , Nakanuma Yasuni
Published: November 2012

Background/Aims

We have reported the involvement of deregulated autophagy and subsequent cellular senescence in biliary epithelial lesions in primary biliary cirrhosis (PBC). Given that mitochondria are a major target of autophagy, we hypothesized that deregulated autophagy of mitochondria may be involved in autoimmune pathogenesis in PBC.

Methods

We examined immunohistochemically the expression of pyruvate dehydrogenase complex‐E2 component (PDC‐E2) and cytochrome c oxidase, subunit I (CCO), in livers taken from patients with PBC (n = 42) and control livers (n = 76). The colocalization of mitochondrial antigens with an autophagy marker microtubule‐associated protein‐light chain 3β (LC3), a deregulated autophagy marker p62/sequestosome‐1 (p62) and a lysosomal marker LAMP‐1 was examined by double immunofluorescence. We examined the colocalization of mitochondrial antigens with LC3, p62 and LAMP‐1 and the cell‐surface expression of PDC‐E2 in cultured biliary epithelial cells (BECs) treated with various stresses.

Results

Intense granular expression of PDC‐E2 and CCO was seen in the damaged small bile ducts (SBDs) in PBC and the expression was significantly more frequent in PBC than in control livers (P < 0.01). The granular expression of mitochondrial antigens was colocalized with LC3 in damaged SBDs in PBC. The accumulation of LC3‐expressing punctae colocalized with PDC‐E2 and CCO was significantly more increased in cultured BECs treated with various stresses. The cell‐surface expression of PDC‐E2 was induced by various stresses in BECs.

Conclusion

Deregulated autophagy may contribute to the abnormal expression of mitochondrial antigens and may be involved in the autoimmune pathogenesis of bile duct lesions in PBC.