bluuebunny/crossref_metadata_2025 huggingface dataset:
NADPH oxidase (NOX) isoforms are inhibited by celastrol with a dual mode of action
Authors: Jaquet Vincent , Marcoux Julien , Forest Eric , Leidal Kevin G , McCormick Sally , Westermaier Yvonne , Perozzo Remo , Plastre Olivier , Fioraso‐Cartier Laetitia , Diebold Becky , Scapozza Leonardo , Nauseef William M , Fieschi Franck , Krause Karl‐Heinz , Bedard Karen
Published: April 2011

BACKGROUND Celastrol is one of several bioactive compounds extracted from the medicinal plant Tripterygium wilfordii. Celastrol is used to treat inflammatory conditions, and shows benefits in models of neurodegenerative disease, cancer and arthritis, although its mechanism of action is incompletely understood.

EXPERIMENTAL APPROACH Celastrol was tested on human NADPH oxidases (NOXs) using a panel of experiments: production of reactive oxygen species and oxygen consumption by NOX enzymes, xanthine oxidase activity, cell toxicity, phagocyte oxidase subunit translocation, and binding to cytosolic subunits of NOX enzymes. The effect of celastrol was compared with diphenyleneiodonium, an established inhibitor of flavoproteins.

KEY RESULTS Low concentrations of celastrol completely inhibited NOX1, NOX2, NOX4 and NOX5 within minutes with concentration–response curves exhibiting higher Hill coefficients and lower IC50 values for NOX1 and NOX2 compared with NOX4 and NOX5, suggesting differences in their mode of action. In a cell‐free system, celastrol had an IC50 of 1.24 and 8.4 µM for NOX2 and NOX5, respectively. Cytotoxicity, oxidant scavenging, and inhibition of p47phox translocation could not account for NOX inhibition. Celastrol bound to a recombinant p47phox and disrupted the binding of the proline rich region of p22phox to the tandem SH3 domain of p47phox and NOXO1, the cytosolic subunits of NOX2 and NOX1, respectively.

CONCLUSIONS AND IMPLICATIONS These results demonstrate that celastrol is a potent inhibitor of NOX enzymes in general with increased potency against NOX1 and NOX2. Furthermore, inhibition of NOX1 and NOX2 was mediated via a novel mode of action, namely inhibition of a functional association between cytosolic subunits and the membrane flavocytochrome.
SPA0355, a thiourea analogue, inhibits inflammatory responses and joint destruction in fibroblast‐like synoviocytes and mice with collagen‐induced arthritis
Authors: Lee YR , Hwang JK , Lee HS , Cheon YJ , Ryu JH , Lee SI , Kwak HB , Lee SM , Kim JS , Park JW , Jeon R , Park BH
Published: April 2011

BACKGROUND AND PURPOSE NF‐κB has been implicated as a therapeutic target for the treatment of rheumatoid arthritis. We previously synthesized a thiourea analogue, SPA0355, which suppressed NF‐κB activity. Here we have assessed the anti‐inflammatory and anti‐arthritic effects of SPA0355.

EXPERIMENTAL APPROACH We evaluated the effects of SPA0355 on human rheumatoid fibroblast‐like synoviocytes in vitro and on collagen‐induced arthritis (CIA) in mice in vivo.

KEY RESULTS In vitro experiments demonstrated that SPA0355 suppressed chemokine production, matrix metalloproteinase secretion and cell proliferation induced by TNF‐α in rheumatoid fibroblast‐like synoviocytes. In addition, SPA0355 inhibited osteoclast differentiation induced by macrophage colony‐stimulating factor and the receptor activator of NF‐κB ligand, in bone marrow macrophages. Mice with CIA that were pretreated with SPA0355 had a lower cumulative disease incidence and severity of arthritis, based on hind paw thickness, radiological and histopathological findings, and inflammatory cytokine levels, than mice treated with vehicle. Mice treated with SPA0355, after the onset of CIA, also showed significantly decreased disease incidence and joint oedema. The in vitro and in vivo protective effects of SPA0355 were mediated by inhibition of the NF‐κB signalling pathway.

CONCLUSION AND IMPLICATIONS Taken together, these results suggested that using SPA0355 to block the NF‐κB pathway in rheumatoid joints reduced both the inflammatory responses and tissue destruction. Therefore, SPA0355 may have therapeutic value in preventing or delaying joint destruction in patients with rheumatoid arthritis.
Inhibition of COX‐2 expression by endocannabinoid 2‐arachidonoylglycerol is mediated via PPAR‐γ
Authors: Du Huizhi , Chen Xiaolei , Zhang Jian , Chen Chu
Published: April 2011

BACKGROUND AND PURPOSE Endocannabinoids have both anti‐inflammatory and neuroprotective properties against harmful stimuli. We previously demonstrated that the endocannabinoid 2‐arachidonoylglycerol (2‐AG) protects hippocampal neurons by limiting the inflammatory response via a CB1 receptor‐dependent MAPK/NF‐κB signalling pathway. The purpose of the present study was to determine whether PPARγ, an important nuclear receptor, mediates 2‐AG‐induced inhibition of NF‐κB phosphorylation and COX‐2 expression, and COX‐2‐enhanced miniature spontaneous excitatory postsynaptic currents (mEPSCs).

EXPERIMENTAL APPROACH By using a whole‐cell patch clamp electrophysiological recording technique and immunoblot analysis, we determined mEPSCs, expression of COX‐2 and PPARγ, and phosphorylation of NF‐kB in mouse hippocampal neurons in culture.

KEY RESULTS Exogenous and endogenous 2‐AG‐produced suppressions of NF‐κB‐p65 phosphorylation, COX‐2 expression and excitatory synaptic transmission in response to pro‐inflammatory interleukin‐1β (IL‐1β) and LPS were inhibited by GW9662, a selective PPARγ antagonist, in hippocampal neurons in culture. PPARγ agonists 15‐deoxy‐Δ12,14‐prostaglandin J2 (15d‐PGJ2) and rosiglitazone mimicked the effects of 2‐AG on NF‐κB‐p65 phosphorylation, COX‐2 expression and mEPSCs, and these effects were eliminated by antagonism of PPARγ. Moreover, exogenous application of 2‐AG or elevation of endogenous 2‐AG by inhibiting its hydrolysis with URB602 or JZL184, selective inhibitors of monoacylglycerol lipase (MAGL), prevented the IL‐1β‐ and LPS‐induced reduction of PPARγ expression. The 2‐AG restoration of the reduced PPARγ expression was blocked or attenuated by pharmacological or genetic inhibition of the CB1 receptor.

CONCLUSIONS AND IMPLICATIONS Our results suggest that CB1 receptor‐dependent PPARγ expression is an important and novel signalling pathway in endocannabinoid 2‐AG‐produced resolution of neuroinflammation in response to pro‐inflammatory insults.

LINKED ARTICLES This article is part of a themed issue on Cannabinoids in Biology and Medicine. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue‐7
QRS Fragmentation Is Not Associated with Poor Response to Cardiac Resynchronization Therapy
Authors: Rickard John , Zardkoohi Omeed , Popovic Zoran , Verhaert David , Sraow Dan , Baranowski Bryan , Martin David O. , Grimm Richard A. , Chung Mina K. , Tchou Patrick , Lindsay Bruce A. , Wilkoff Bruce L.
Published: April 2011

Background: QRS fragmentation (fQRS) has been shown to be a marker of scar in patients with left ventricular dysfunction. Whether fQRS is associated with progressive left ventricular remodeling and increased mortality in patients receiving cardiac resynchronization therapy (CRT) is unclear.

Methods: We reviewed the preimplant and follow‐up echocardiograms in 233 patients undergoing the new implantation of a CRT device between December 2001 and November 2006. Patients were included if they had a pre‐CRT ECG with appropriate filter settings (filter 0.16–100 or 0.16–150 Hz, 25 mm/s, 10 mm/mV), a left ventricular ejection fraction (LVEF) ≤40%, and New York Heart Association class II–IV symptoms on standard medical therapy. The 12‐lead electrocardiogram (ECG) was interpreted by two blinded reviewers for the presence of fQRS. Remodeling end points, including changes in LVEF and left ventricular end‐diastolic (LVEDV) and systolic (LVESV) volumes, were compared between patients with and without contiguous fQRS, and an assessment of all‐cause mortality was made.

Results: Two hundred thirty‐two patients met inclusion criteria, of which 50 demonstrated fQRS in contiguous leads. There was no difference in improvement in LVEF (%) (7.9 ± 12.9 vs 6.8 ± 11.0, P = 0.60) or reduction in LVEDV (mL) (−30.1 ± 57.2 vs −15.7 ± 47.6) or LVESV (mL) (−33.7 ± 58.1 vs −22.7 ± 50.6, P = 0.40) between patients with and without contiguous fQRS. At a mean follow‐up of 4.4 ± 1.9 years, there were a total of 89 deaths, 22 (44.0%) in patients with contiguous fQRS and 67 (36.8%) without (log rank P = 0.31).

Conclusions: QRS fragmentation is not a predictor of progressive ventricular remodeling or mortality in heart failure patients undergoing CRT.

Ann Noninvasive Electrocardiol 2011;16(2):165–171
Epinephrine Bolus Test in Detecting Long QT Syndrome Mutation Carriers with Indeterminable Electrocardiographic Phenotype
Authors: Hekkala Anna‐Mari , Swan Heikki , Viitasalo Matti , Väänänen Heikki , Toivonen Lauri
Published: April 2011

Background: In long QT syndrome (LQTS), prolonged and heterogeneous ventricular repolarization predisposes to serious arrhythmias. We examined how QT intervals are modified by epinephrine bolus in mutation carriers of three major LQTS subtypes with indefinite QT interval.

Methods: Genotyped, asymptomatic subjects with LQTS type 1 (LQT1; n = 10; four different KCNQ1 mutations), type 2 (LQT2; n = 10; three different HERG mutations), and type 3 (LQT3; n = 10; four different SCN5A mutations), and healthy volunteers (n = 15) were examined. Electrocardiogram was recorded with body surface potential mapping system. After an epinephrine 0.04 μg/kg bolus QT end, QT apex, and T‐wave peak‐to‐end (Tpe) intervals were determined automatically as average of 12 precordial leads. Standard deviation (SD) of the 12 channels was calculated.

Results: Heart rate increased 26 ± 10 bpm with epinephrine bolus, and similarly in all groups. QT end interval lengthened, and QT apex interval shortened in LQTS and normals, leading to lengthening of Tpe interval. However, the lengthening in Tpe was larger in LQTS than in normals (mean 32 vs 18 ms; P < 0.05) and SD of QT apex increased more in LQTS than in normals (mean 23 vs 7 ms; P < 0.01). The increase in Tpe was most pronounced in LQT2, and in SD of QT apex in LQT1 and LQT2.

Conclusions: Abrupt adrenergic stimulation with a moderate dose of exogenous epinephrine affects ventricular repolarization in genotype‐specific fashion facilitating distinction from normals. This delicate modification may help in diagnosing electrocardiographically silent mutation carriers when screening LQTS family members.

Ann Noninvasive Electrocardiol 2011;16(2):172–179
Use of Adenosine Test for the Exclusion of Preexcitation Syndrome in Asymptomatic Individuals
Authors: Grossman Alon , Wand Ori , Matezki Shlomi , Kerner Arthur , Assa Amit , Glikson Michael
Published: April 2011

Background: Resting electrocardiogram is a routine procedure for the identification of potentially fatal conditions, including preexcitation syndrome (PES). Intravenous adenosine is a sensitive and specific means of exposing inapparent pathways in such patients. Yet, it may not be sensitive when complete atrioventricular (AV) block is not achieved because a low dose of adenosine is used. We evaluated the yield of a high‐dose adenosine test that achieved complete AV nodal block for unmasking inapparent pathway in a healthy population.

Methods: We retrospectively reviewed all Israeli air force (IAF) academy candidates who were referred to adenosine test based on a cardiologist's suspicion of PES. The results of the adenosine test were recorded, including the adenosine dose required to achieve complete AV block. The medical records of the subjects were reviewed to identify any adverse cardiovascular outcome.

Results: Fifty‐nine subjects who underwent adenosine test were followed for 35.42 ± 24 months. Complete AV block was achieved in all subjects with an average adenosine dose of 22.51 ± 12.67 mg. None of the subjects had evidence of an inapparent pathway. All subjects completed military service without adverse outcomes.

Conclusions: The vast majority of young patients with a short PR interval do not have evidence of an accessory pathway and have a favorable prognosis. Thus, the yield of adenosine test in young combat recruits is questionable. Yet, if there is no evidence of an accessory pathway while achieving complete AV block on adenosine test, the chance of an accessory pathway being present is probably extremely low.

Ann Noninvasive Electrocardiol 2011;16(2):180–183
Apoptosis, proliferation and Fas ligand expression in placental trophoblast from pregnancies complicated by HELLP syndrome or pre‐eclampsia
Authors: PRUSAC IVANA KUZMIC , ZEKIC TOMAS SANDRA , ROJE DAMIR
Published: April 2011

Objective. To investigate apoptosis, proliferation and Fas ligand expression of placental trophoblast in the hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome and in pre‐eclampsia (PE), and to compare this with normal pregnancies. Design. Prospective study. Setting. University hospital in Croatia. Sample. Placentae from women with HELLP syndrome (n=10), PE (n=10) and normal pregnancies (n=10). Methods. The HELLP syndrome was diagnosed with platelets <100×109/L, aspartate aminotransferase (AST) and alanine transaminase (ALT) >70U/L and lactic acid dehydrogenase (LDH) > 600U/L. Pre‐eclampsia was diagnosed at blood pressure >140/90mmHg, with proteinuria >300mg/L/24hours. For detection of apoptosis and proliferation in villous trophoblast, antibodies M30 and Ki‐67 were used. Expression of Fas ligand was assessed using immunohistochemistry and the semiquantitative HSCORE method. Main Outcome Measures. Apoptosis, proliferation and Fas ligand expression in villous trophoblast. Results. Apoptosis, proliferation and Fas ligand expression were higher in villous trophoblast in HELLP syndrome than in the PE group (p=0.015, p=0.018 and p=0.002, respectively) and the control group (p=0.000, p=0.012 and p=0.049, respectively). Placentae from the PE group had higher levels of apoptosis (p=0.019), lower Fas ligand expression (p=0.029) and no difference in proliferation (p=0.887) compared with the control group. Conclusions. There is an increase in apoptosis, proliferation and Fas ligand expression in placentae from women with HELLP syndrome compared with placentae from PE and normal pregnancies. Our findings indicate the possibility of differential mechanisms behind HELLP syndrome and PE.
Risk factors for patellar tendinopathy in basketball and volleyball players: a cross‐sectional study
Authors: van der Worp H. , van Ark M. , Zwerver J. , van den Akker‐Scheek I.
Published: April 2011

Patellar tendinopathy (PT) has a multifactorial etiology, and many possible risk factors have been described in the literature. The findings are conflicting, though, and most research has been conducted on elite athletes. The aim of the current study is to determine the risk factors for PT in a large representative sample of basketball and volleyball players. Separate risk factors for men and women, basketball and volleyball players, and athletes with unilateral and bilateral PT were identified. All basketball and volleyball players between ages 18 and 35 from the Dutch Basketball Association and the Dutch Volleyball Association were invited to complete an online questionnaire on knee complaints and risk factors for PT. The logistic regression analyses included 2224 subjects. The risk factors for PT were age, playing at the national level, being male and playing volleyball (compared with playing basketball). The risk factors for men and women were comparable. Among volleyball players, outside hitters and middle blockers/hitters had an increased risk compared with setters. For basketball players, no risk factors could be identified. No differences in the risk factors were found between athletes with unilateral and bilateral PT. These findings should be taken into account for prevention and rehabilitation purposes.
Altered cell metabolism in tissues of the knee joint in a rabbit model of Botulinum toxin A‐induced quadriceps muscle weakness
Authors: Leumann A. , Longino D. , Fortuna R. , Leonard T. , Vaz M. A. , Hart D. A. , Herzog W.
Published: April 2011

Quadriceps muscle weakness is frequently associated with knee injuries in sports. The influence of quadriceps weakness on knee joint homeostasis remains undefined. We hypothesized that quadriceps weakness will lead to tissue‐specific alterations in the cell metabolism of tissues of the knee. Quadriceps weakness was induced with repetitive injections of Botulinum toxin A in six 1‐year‐old New Zealand White rabbits for 6 months. Five additional animals served as controls with injections of saline/dextrose. Muscle weakness was assessed by muscle wet mass, isometric knee extensor torque, and histological morphology analysis. Cell metabolism was assessed for patellar tendon, medial and lateral collateral ligament, and medial and lateral meniscus by measuring the total RNA levels and specific mRNA levels for collagen I, collagen III, MMP‐1, MMP‐3, MMP‐13, TGF‐β, biglycan, IL‐1, and bFGF by reverse transcription and polymerase chain reaction. While the total RNA levels did not change, tissue‐specific mRNA levels were lower for relevant anabolic and catabolic molecules, indicating potential changes in tissue mechanical set points. Quadriceps weakness may lead to adaptations in knee joint tissue cell metabolism by altering a subset of anabolic and catabolic mRNA levels corresponding to a new functional and metabolic set point for the knee that may contribute to the high injury rate of athletes with muscle weakness.
Secular trends in aerobic fitness performance in a cohort of Norwegian adolescents
Authors: Dyrstad S. M. , Berg T. , Tjelta L. I.
Published: April 2011

The purpose of the present study was to compare 3000 m running test results between 1969 and 2009 in a cohort of Norwegian high school pupils. Between 1969 and 2009, a total of 4981 (2827 boys) 3000 m running tests were collected from two Norwegian senior high schools. One‐way ANOVA with Tukey's post hoc test was used to analyze the differences in the running times between the different decades. The running times have increased by 10% and 6% from the 1980s to the 2000s for boys and girls, respectively. The distribution showed a decline in aerobic fitness performance for all deciles. The largest negative change in difference was found for pupils with the poorest aerobic fitness level in both boys and girls. The cohort of 16‐ to 18‐year‐old boys and girls in the decade 2000–2009 had a poorer aerobic fitness performance in the 3000 m running test compared with earlier decades. The decline in running performance was greater for boys than girls, and the gap between the most and the least fit is becoming considerably larger.
Effects of eccentric training on hand strength in subjects with lateral epicondylalgia: a randomized‐controlled trial
Authors: Söderberg J. , Grooten W. J. , Äng B. O.
Published: April 2011

The main aim of this study was to evaluate the short‐term effects of daily eccentric exercises on functional pain‐free hand strength in subjects with long‐term lateral epicondylalgia. Forty‐two subjects with lateral epicondylalgia were randomly assigned either to a 6‐week home exercise regimen receiving eccentric training for their wrist extensors and a forearm band or to a control group receiving a forearm band only. The main outcomes were pain‐free hand‐grip and wrist‐extensor strength at mid‐ and end‐intervention follow‐ups, 3 and 6 weeks after inclusion, respectively. Secondary outcomes were a change in the proportion of cases with epicondylalgia and ratings of perceived pain (VAS) at follow‐up. Thirty‐seven (88%) subjects completed both the mid‐ and the end‐intervention follow‐up. Exercise members had significantly higher pain‐free hand‐grip (P=0.025) and wrist‐extensor strength (P<0.001) at the end of follow‐up, although there was no such effect at mid‐intervention. Regression analysis showed a reduction in the proportion of cases in the exercise group at the end of follow‐up (P=0.035). However, no between‐groups effect emerged for perceived pain. These data suggest that the daily home eccentric exercise regimen is effective in increasing functional pain‐free grip strength and reducing cases suffering from lateral epicondylalgia. However, no effect emerged for global perceived pain during the last week.
A Sagittarius-induced origin for the Monoceros ring
Authors: Michel-Dansac Léo , Abadi Mario G. , Navarro Julio F. , Steinmetz Matthias
Published: April 2011

The Monoceros ring is a collection of stars in nearly circular orbits at roughly 18 kpc from the Galactic Centre. It may have originated (i) as the response of the disc to perturbations excited by satellite companions or (ii) from the tidal debris of a disrupted dwarf galaxy. The metallicity of Monoceros stars differs from that of disc stars at comparable Galactocentric distances, an observation that disfavours the first scenario. On the other hand, circular orbits are difficult to accommodate in the tidal-disruption scenario, since it requires a satellite which at the time of disruption was itself in a nearly circular orbit. Such satellite could not have formed at the location of the ring and, given its low mass, dynamical friction is unlikely to have played a major role in its orbital evolution. We search cosmological simulations for low-mass satellites in nearly circular orbits and find that they result, almost invariably, from orbital changes induced by collisions with more massive satellites: the radius of the circular orbit thus traces the galactocentric distance of the collision. Interestingly, the Sagittarius dwarf, one of the most luminous satellites of the Milky Way, is in a polar orbit that crosses the Galactic plane at roughly the same Galactocentric distance as Monoceros. We use idealized simulations to demonstrate that an encounter with Sagittarius might well have led to the circularization and subsequent tidal demise of the progenitor of the Monoceros ring.
The 17-min orbital period in the ultracompact X-ray binary 4U 0513-40
Authors: Fiocchi M. , Bazzano A. , Natalucci L. , Landi R. , Ubertini P.
Published: April 2011

The ultracompact low-mass X-ray binary 4U 0513-40 in the globular cluster NGC1851 exhibits large amplitude X-ray flux variations with spectral changes from low/hard to high/soft states which have not been reported previously in other ultracompact X-ray binaries. Using BeppoSAX, Chandra and XMM-Newton archival data together with recent INTEGRAL observations, we reveal a clear sinusoidal periodic signal with a period of ∼17 min when the source is in a typical high/soft state with a dominant soft thermal component. The periodicity disappears when the source is in a low/hard state and the thermal soft component is not required any more to model the data. These properties indicate the orbital nature of the detected signal and imply an high inclination angle of the binary system (>80°).
Prevalence of major enteric pathogens in Australian dairy calves with diarrhoea
Authors: Izzo MM , Kirkland PD , Mohler VL , Perkins NR , Gunn AA , House JK
Published: April 2011

Objective Determine the prevalence of the major enteric pathogens in dairy and dairy beef calves with diarrhoea in Australia.

Design Cross‐sectional study.

Methods Faecal samples from 84 Australian dairy and dairy beef properties (597 samples) were screened for rotavirus and coronavirus using real‐time reverse transcription polymerase chain reaction, forSalmonellaspp. using selective enrichment faecal culture, and for enterotoxigenicEscherichia coli(K99) andCryptosporidium parvumusing a commercial enzyme‐linked immunosorbent assay. A logistic regression with random effects model was used to compare prevalence of pathogens in dairy and dairy beef operations.

Results Enteric pathogens were isolated from 97.6% of outbreaks and 95.0% of samples. Rotavirus was the most common pathogen identified (477/597, 79.9%) followed byC.parvum(349/597, 58.5%),Salmonellaspp. (142/597, 23.8%), coronavirus (129/597, 21.6%) andE. coliK99 (104/597, 17.4%). Multiple pathogens were identified on 96.4% of farms and from 71.0% of samples. Samples from dairy beef properties were more likely to have multiple pathogens than dairy properties (P < 0.05), whereas rotavirus andSalmonellaspp. were more likely to be identified in samples collected from dairy beef than dairy properties (P < 0.05).

Conclusion Most outbreaks of calf diarrhoea in dairy and dairy beef operations involve multiple pathogens. Rotavirus andC. parvumwere the most frequently identified pathogens across production systems.Salmonellaspp. and rotavirus were more frequently identified in dairy beef operations.
Minimising the development of anthelmintic resistance, and optimising the use of the novel anthelmintic monepantel, for the sustainable control of nematode parasites in Australian sheep grazing systems
Authors: Dobson RJ , Hosking BC , Besier RB , Love S , Larsen JWA , Rolfe PF , Bailey JN
Published: April 2011

Objective  To compare the risk of different treatment scenarios on selecting for anthelmintic resistance on Australian sheep farms.

Design  A computer simulation model predicted populations of Trichostrongylus colubriformis, Haemonchus contortus or Teladorsagia (Ostertagia) circumcincta, and the frequency of anthelmintic resistance genes.

Method  Nematode populations and the progression of drug resistance for a variety of treatment options and management practices in sheep‐rearing areas of Western Australia (WA), Victoria (VIC) and New South Wales (NSW) were simulated. A scoring system was devised to measure the success of each option in delaying resistance to each anthelmintic and in controlling nematode populations.

Results  The best option at all sites was combining the new anthelmintic (monepantel) with a triple mixture of benzimidazole, levamisole and abamectin (COM). The next best option was: in NSW, rotation at each treatment between monepantel, moxidectin and COM; in VIC, rotation at each treatment between monepantel and COM; and in WA, rotation at each treatment between monepantel (used in winter) and COM or moxidectin (used in summer–autumn). In WA, rapid selection for resistance occurred as a consequence of summer–autumn treatments; however, if a small percentage of adult stock were left untreated then this selection could be greatly reduced. Despite purposely assuming relatively high resistance to benzimidazole and levamisole, COM was still effective in controlling worms and delaying resistance.

Conclusions  Because of cost constraints, it may not be feasible or profitable for producers to always use the combination of all drugs. However, the second‐ and third‐best options still considerably slowed the development of anthelmintic resistance.
Unusual maxillary branch paraesthesia after an articaine inferior alveolar nerve block
Authors: Koshal S. , Eyeson J.D. , Patel J.
Published: April 2011

Background:  There are a number of reported complications of inferior alveolar nerve (IAN) block administration. One of these complications is that of neurosensory disturbance, which may be attributed to the block technique or type of local anaesthetic used. The authors present a case of an unusual and largely unreported complication of maxillary branch paraesthesia following an articaine IAN block.

Case description:  A patient developed neurosensory disturbance of the facial nerve, maxillary and mandibular divisions of the trigeminal nerve following the administration of an IAN block for restorative dentistry. He returned 3 days after the IAN block with anaesthesia of both upper and lower left lip, cheek, tongue and loss of taste on the ipsilateral side. Neurosensory testing a year post‐injury still showed neurosensory impairment in the maxillary and mandibular distributions of the trigeminal nerve.

Discussion:  The mechanism of nerve injury post‐IAN administration is explored and the relevance of articaine local anaesthetic solution is considered.
Correlation of worldwide incidence of type 1 diabetes (DiaMond) with prevalence of asthma and atopic eczema (ISAAC)
Authors: Fsadni Peter , Fsadni Claudia , Fava Stephen , Montefort Stephen
Published: April 2011

Introduction:  Environmental factors play a role in pathogenesis of both type 1 diabetes and atopic disease but they remain incompletely understood. T cell‐mediated responses primarily of the T helper type 1 (Th1) are involved in type 1 diabetes while T helper type 2 (Th2) responses favour allergic disease. This TH 1/TH 2 paradigm is currently the source of much controversy in various studies.

Objective:  The aim of the study was to compare the reported country incidence of type 1 diabetes with the prevalence of atopic disease.

Methods:  The prevalence of wheeze, rhinitis, rhinoconjunctivitis and atopic eczema in the preceding 12 months in the 13‐ to 14‐year‐old age group was taken from The International Study of Asthma and Allergies in Childhood phase 1 study. These were compared to the age specific incidence of type 1 diabetes in children per 100 000 per year obtained from the Diabetes Mondiale Project Group study from those countries participating in both studies. Data collected from these 31 countries together with latitude was analysed using a Pearson correlation and significance analysis. A multiple regression analysis determined the confounding effect of latitude.

Results:  The incidence of type 1 diabetes was found to have a positive correlation with both wheezing (P = 0.009) and atopic eczema (P < 0.01). There was a no correlation between the incidence of type 1 diabetes and the prevalance of rhinitis (r = 0.02, P = 0.88) or of rhinoconjunctivitis (r = 0.026, P = 0.88). Latitude correlated negatively with type 1 diabetes and positively with rhinitis and rhinoconjnctuvits; it was not significantly correlated with wheeze or eczema. Regression analysis showed that latitude is a significant confounding factor in the correlation of rhinitis (P value <0.0008) and rhinoconjunctivitis (P value <0.0003) with diabetes.

Conclusions:  The study suggests that common environmental and/or genetic factors predispose to type 1 diabetes, wheezing and atopic eczema while factors predisposing to rhinitis and rhinoconjunctivitis appear to be distinct from those predisposing to type 1 diabetes.

Please cite this paper as: Fsadni P, Fsadni C, Fava S and Montefort S. Correlation of worldwide incidence of type 1 diabetes (DiaMond) with prevalence of asthma and atopic eczema (ISAAC). Clin Respir J 2012; 6: 18–25.
Inspiratory conductance: an alternative index of the relationship between inspiratory effort and airflow with potential for clinical use
Authors: Allen Stephen , Brown Ian , Khattab Ahmed , Bagust Jeff
Published: April 2011

Introduction and Objectives:  There is a need for a measure of airway status that is easier for patients to use. If airflow is briefly occluded at the onset of inspiration, the maximum rate of pressure fall, dP/dtmax can be measured. After the occlusion is released, the maximum rate of change of inspiratory airflow (dF/dtmax) can be measured and expressed as a ratio of dP/dtmax to generate an index of inspiratory conductance (IC). We explored the characteristics of IC as a preliminary step towards developing it as an easy‐to‐use alternative.

Methods:  To measure IC, we constructed an apparatus consisting of a pneumotachograph, a low‐resistance spring‐loaded valve and a pressure transducer to measure airflow and pressure drop at the start of inspiration. We studied 30 healthy adults to define the values of the index, its stability and its response to external inspiratory resistive loads.

Results:  Mean IC was 2.49 (SD 0.96) Ls−1kPa−1, with no significant difference between men and women. The index was stable with a mean long‐term variation of 11.25% around the normalised mean, compared with 2.1% for forced expiratory volume in 1 s (FEV1) and within‐test variation <5%. In response to external resistive loading, IC fell in a non‐linear but consistent manner from 3.96 (0.32) to 0.96 (0.10) Ls−1kPa−1 across an added resistance range of 0–70 kPasL−1.

Conclusion:  We showed that IC was measurable with a minimal need for subject participation. It was stable and reproducible in normal individuals and responded to added inspiratory resistive loads in a way that suggested it could be of clinical utility.

Please cite this paper as: Allen S, Brown I, Khattab A and Bagust J. Inspiratory conductance: an alternative index of the relationship between inspiratory effort and airflow, with potential for clinical use. Clin Respir J 2012; 6: 26–34.
Integumental reddish‐violet coloration owing to novel dichromatic chromatophores in the teleost fish, Pseudochromis diadema
Authors: Goda Makoto , Ohata Mihoko , Ikoma Hayato , Fujiyoshi Yoshinori , Sugimoto Masazumi , Fujii Ryozo
Published: April 2011

In the reddish‐violet parts of the skin of the diadema pseudochromis Pseudochromis diadema, we found novel dichromatic chromatophores with a reddish pigment and reflecting platelets. We named these novel cells ‘erythro‐iridophores’. In standard physiological solution, erythro‐iridophores displayed two hues, red and dark violet when viewed with an optical microscope under ordinary transmission light and epi‐illumination optics, respectively. Under transmission electron microscopy, however, we observed no typical red chromatosomes, i.e., erythrosomes, in the cytoplasm. High‐performance thin‐layer chromatography (HPTLC) analysis of the pigment eluted from the erythro‐iridophores indicated that carotenoid is the main pigment generating the reddish color. Furthermore, when the irrigating medium was a K+‐rich saline solution, the color reflected from the erythro‐iridophores changed from dark violet to sky blue, but the red coloration remained. The motile activities of the erythro‐iridophores may participate in the changes in the reddish‐violet shades of the pseudochromis fish.
Tadalafil Administered Once Daily for Treatment of Lower Urinary Tract Symptoms in Korean men with Benign Prostatic Hyperplasia: Results from a Placebo‐Controlled Pilot Study Using Tamsulosin as an Active Control
Authors: KIM Sae Chul , PARK Jong Kwan , KIM Sae Woong , LEE Sung Won , AHN Tai Young , KIM Je Jong , PAICK Jae Seung , PARK Nam Cheol , PARK Kwangsung , MIN Kweon Sik , KRAUS Stephen R. , SECREST Roberta J. , ELION‐MBOUSSA Albert , VIKTRUP Lars
Published: April 2011

Objectives: Assess the efficacy and safety of once‐daily tadalafil or tamsulosin versus placebo during 12 weeks on lower urinary tract symptoms (LUTS) in Korean men with benign prostatic hyperplasia (BPH).

Methods: Following a 4‐week placebo run‐in period, 151 Korean men were randomly assigned to receive once‐daily tadalafil 5 mg, tamsulosin 0.2 mg, or placebo for 12 weeks.

Results: The International Prostate Symptom Score (IPSS) least squares mean changes from baseline to endpoint were numerically but not significantly improved in the tadalafil (−5.8) and tamsulosin (−5.4) groups compared with placebo (−4.2, P > 0.05). Decreases in IPSS obstructive and irritative subscores, IPSS Quality of Life score, and BPH Impact Index from baseline to endpoint were largest in the tadalafil group followed by tamsulosin, though none separated significantly from placebo. Increases in maximum urinary flow rate were small and not significantly different than placebo; the increase was largest in the tadalafil group (2.5 mL/sec), followed by the placebo (2.3 mL/sec) and tamsulosin (2.1 mL/sec) groups. The percentage of subjects reporting at least one treatment‐emergent adverse event was 26.5, 13.7 and 3.9% in the tamsulosin, tadalafil and placebo groups, respectively.

Conclusions: In this pilot study in Korean men, those with BPH and treated with tadalafil 5 mg or tamsulosin 0.2 mg once daily experienced a reduction in LUTS, which was numerically (but not statistically) significant compared with the placebo. Tadalafil was well tolerated and few subjects discontinued the study due to treatment‐emergent adverse events. Larger studies in Asian men with BPH and LUTS treated with phosphodiesterase type 5 inhibitors are needed.
Comparison of the Effects by Obybutynin and Tolterodine on Spina Bifida Patients: A Pilot Crossover Study
Authors: KANEMATSU Akihiro , JOHNIN Kazuyoshi , YOSHIMURA Koji , IMAMURA Masaaki , OGAWA Osamu
Published: April 2011

Objectives: To compare the effects of obybutynin and tolterodine in neurogenic bladder patients with spina bifida in a crossover study.

Methods: Seven myelomeningocele and one spinal lipoma cases, maintained with obybutynin and clean intermittent catheterization for more than 60 months, were enrolled. Age ranged from 8 to 23 years (mean 12.0, male/ female = 2/6). After 2 weeks of washout period, obybutynin (0.3 mg/kg, maximum 12 mg) or tolterodine (0.12 mg/kg, maximum 4 mg) was administered for 4 weeks, and then switched to the other drug for 4 weeks. At the end of the three periods, the patients and/or parents documented urinary storage status and adverse effects, and urodynamic study was performed.

Results: In seven cases undergoing sequential urodynamic study, the baseline compliance of the patients (6.81 ± 1.83) increased to 9.98 ± 4.97 by obybutynin and 10.16 ± 2.53 by tolterodine (P < 0.05 for each). Better compliance was noted in two cases with tolterodine and in two cases with obybutynin. Stronger adverse effects were reported in three out of eight patients (37.5%) by obybutynin and three out of eight patients (37.5%) by tolterodine. Although storage effect and side effects were equivalent for total patients, markedly diverse response was noted for each patient, with five choosing tolterodine and three choosing obybutynin.

Conclusions: Individualized evaluation is required for optimal choice of anticholinergics.
Information Content of Changes in Index Composition*
Authors: Yun Jooyoung , Kim Tong S.
Published: April 2011

This study examines the effect of changes in the Korea Stock Exchange Price Index to determine the main cause of abnormal return behavior. It tests five prevailing hypotheses individually and simultaneously using both added and deleted stocks during the event window. We find evidence of permanent price effects and of temporary price pressure around the effective date. The results show that the return behavior of added and deleted stocks can be explained by the information content hypothesis. The indexing methodology conveys the valuable information that the added stocks showed good performance and better earnings relative to both the market and the same industry average while the deleted stocks showed the opposite. In conclusion, member changes in the Korea Stock Exchange Price Index are not information‐free events.
Dark Side of Institutional Shareholder Activism in Emerging Markets: Evidence from China’s Split Share Structure Reform*
Authors: Zeng Yamin , Yuan Qingbo , Zhang Junsheng
Published: April 2011

This study aims to investigate the role that institutional investors played exploiting the split share structure reform launched in 2005 in China. Since that time, non‐tradable majority shareholders have had to compensate minority tradable shareholders to obtain the rights to transfer their shares in the capital markets. The compensation ratio proposed by non‐tradable majority shareholders needs to be approved in at least two‐thirds of the votes cast by tradable shareholders, among which the most powerful are the institutional investors. Our study finds that institutional investors actively participate in voting, but their activism is beneficial to majority shareholders rather than minority shareholders. Specifically, we find a significant negative relation between institutional shareholdings and (i) the initial compensation ratio, (ii) the probability and amount of the upward revision of the initial compensation ratio during the bargaining process, and (iii) the final compensation ratio. Collectively, our results suggest that institutional shareholders are more likely to collude rather than fight with controlling shareholders in emerging markets where investor protection is weak.
Effect of source field plate on the characteristics of off-state, step-stressed AlGaN/GaN high electron mobility transistors
Authors: Liu Lu , Kang Tsung Sheng , Cullen David A. , Zhou Lin , Kim Jinhyung , Chang Chih-Yang , Douglas Erica A. , Jang Soohwan , Smith David. J. , Pearton S. J. , Johnson Wayne J. , Ren Fan
Published: April 2011

The effects of source field plates on AlGaN/GaN high electron mobility transistor reliability under off-state stress conditions were investigated using step-stress cycling. The source field plate enhanced the drain breakdown voltage from 55 to 155 V and the critical voltage for off-state gate stress from 40 to 65 V, relative to devices without the field plate. Transmission electron microscopy was used to examine the degradation of the gate contacts. The presence of pits that appeared on both source and drain sides of the gate edges was attributed to the inverse piezoelectric effect. In addition, a thin oxide layer was observed between the Ni gate contact and the AlGaN layer, and both Ni and oxygen had diffused into the AlGaN layer. After step-stress cycling, additional threading dislocations were observed.
“I love my ECPs”: challenges to bridging emergency contraceptive users to more effective contraceptive methods in Ghana: Table 1
Authors: L'Engle Kelly Ladin , Hinson Laura , Chin-Quee Dawn
Published: April 2011

Background and methods

Emergency contraceptive pills (ECPs) are becoming more popular, yet little is known about the contraceptive preferences of women who take ECPs. Women purchasing ECPs were recruited from pharmacies in Accra, Ghana. A total of 24 semi-structured, qualitative interviews were conducted in May 2008.

Results

Nearly all participants preferred ECPs to other contraceptive methods. Although fear of side effects from oral contraceptive pills (OCPs), intrauterine devices and injectables were deterrents to use of those methods, side effects from ECPs were acceptable to this small and highly self-selected group of ECP users. Participants had little knowledge about how other contraceptive methods work and expressed a strong distrust and dislike of condoms.

Discussion and conclusion

Study participants loved their ECPs, despite minor discomforts like bleeding, and most had no concerns about repeated use, though these findings may not apply to women outside Accra or women who obtain ECPs from non-pharmacy settings. Future interventions should work to dispel myths about OCPs, condoms and other modern methods, and focus on basic contraception education.
LOGIC AND ARITHMETIC OPERATIONS WITH A CONSTANT NUMBER OF STEPS IN MEMBRANE COMPUTING
Authors: FUJIWARA AKIHIRO , TATEISHI TAKESHI
Published: April 2011

In the present paper, we propose P systems that work in a constant number of steps. We first propose two P systems for computing multiple input logic functions. An input of the logic functions is a set of n binary numbers of m bits, and an output is a binary number defined by the logic functions. The first and second P systems compute AND and EX-OR functions for the input, and both of the P systems work in a constant number of steps by using O(mn) types of objects, a constant number of membranes, and evolution rules of size O(mn).

Next, we propose a P system for the addition of two binary numbers of m bits. The P system works in a constant number of steps by using O(m) types of objects, a constant number of membranes and evolution rules of size O(m2). We also introduce a P system that computes the addition of two vectors of n binary numbers of m bits by using the above P system as a sub-system. The P system for vector addition works in a constant number of steps by using O(mn) types of objects, a constant number of membranes, and evolution rules of size O(m2n).
GRAPH ORIENTATION TO MAXIMIZE THE MINIMUM WEIGHTED OUTDEGREE
Authors: ASAHIRO YUICHI , JANSSON JESPER , MIYANO EIJI , ONO HIROTAKA
Published: April 2011

We study a new variant of the graph orientation problem called MAXMINO where the input is an undirected, edge-weighted graph and the objective is to assign a direction to each edge so that the minimum weighted outdegree (taken over all vertices in the resulting directed graph) is maximized. All edge weights are assumed to be positive integers. This problem is closely related to the job scheduling on parallel machines, called the machine covering problem, where its goal is to assign jobs to parallel machines such that each machine is covered as much as possible. First, we prove that MAXMINO is strongly NP-hard and cannot be approximated within a ratio of 2 – ε for any constant ε > 0 in polynomial time unless P = NP , even if all edge weights belong to {1, 2}, every vertex has degree at most three, and the input graph is bipartite or planar. Next, we show how to solve MAXMINO exactly in polynomial time for the special case in which all edge weights are equal to 1. This technique gives us a simple polynomial-time [Formula: see text]-approximation algorithm for MAXMINO where wmax and wmin denote the maximum and minimum weights among all the input edges. Furthermore, we also observe that this approach yields an exact algorithm for the general case of MAXMINO whose running time is polynomial whenever the number of edges having weight larger than wmin is at most logarithmic in the number of vertices. Finally, we show that MAXMINO is solvable in polynomial time if the input is a cactus graph.
APPROXIMATING THE DISCRETE RESOURCE SHARING SCHEDULING PROBLEM
Authors: BOUGERET MARIN , DUTOT PIERRE-FRANÇOIS , GOLDMAN ALFREDO , NGOKO YANIK , TRYSTRAM DENIS
Published: April 2011

The goal of this work is to study the portfolio problem which consists in finding a good combination of multiple heuristics given a set of a problem instances to solve. We are interested in a parallel context where the resources are assumed to be discrete and homogeneous, and where it is not possible to allocate a given resource (processor) to more than one heuristic. The objective is to minimize the average completion time over the whole set of instances. We extend in this paper some existing analysis on the problem. More precisely, we provide a new complexity result for the restricted version of the problem, then, we generalize previous approximation schemes. In particular, they are improved using a guess approximation technique. Experimental results are also provided using a benchmark of instances on SAT solvers.
ADAPTIVE DISTRIBUTED MUTUAL EXCLUSION BY DYNAMIC TOPOLOGY SWITCHING
Authors: KARMAKAR SUSHANTA , GUPTA AROBINDA
Published: April 2011

Adaptation is a desirable requirement in a distributed system as it helps the system to perform efficiently under different environments. For many problems, more than one protocol exists, such that one protocol performs better in one environment while the other performs better in another. In such cases, adaptive distributed systems can be designed by dynamically switching between the protocols as the environment changes. In this work we propose an adaptive distributed mutual exclusion scheme that dynamically switches between two token based distributed mutual exclusion protocols; the Raymond's algorithm [15] and the Martin's algorithm [13]. Algorithms are proposed for switching in both directions and their correctness are proved. For each switching algorithm, it is shown that no more than one node can access the shared resource during the switching and no deadlock happens during the switching.