bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacological characterization of the inwardly‐rectifying current in the smooth muscle cells of the rat bladder
Authors: Green Michelle E. , Edwards Gillian , Kirkup Anthony J. , Miller Martin , Weston Arthur H.
Published: July 2012

In freshly‐isolated single cells of the rat bladder detrusor, outwardly‐rectifying and inwardly‐rectifying membrane currents were identified by the whole‐cell voltage‐clamp technique.

The inwardly‐rectifying current (IIR) exhibited features of a cation current permeable to both K+ and Na+ but it was unaffected by changes in extracellular Ca2+. It had an activation threshold close to −60 mV and an estimated reversal potential of −29 mV.

IIR activated slowly with a voltage‐sensitive time‐constant of 69 ms at −140 mV and 209 ms at −100 mV but it did not exhibit time‐dependent inactivation.

IIR was unaffected by tetraethylammonium (up to 20 mM) but it was reduced by extracellular Ba2+(1 mM) and by extracellular Cs+ (1 mM).

IIR was reduced by terikalant (100 μm) and markedly inhibited by ciclazindol (100 μm) although at these concentrations, both agents also reduced outward currents.

IIR was inhibited by ZD7288 (10–100 μm) in a concentration‐dependent manner. At concentrations up to 30 μm, ZD7288 did not reduce the magnitude of outward currents but these were inhibited by 100 μm ZD7288.

In strips of bladder detrusor, spontaneous mechanical activity was increased by ZD7288 (0.3–100 μm) and by ciclazindol (0.3–100 μm) but was unaffected by glibenclamide (1–10 μm).

It is concluded that IIR closely resembles the hyperpolarization‐activated current, Ih, previously described in the smooth muscle of rabbit jejunum and in a variety of other cell types. This current may play an important role in modulating detrusor excitability but this could not be confirmed using the inhibitors ZD7288 and ciclazindol.
Noradrenaline synthesis after sympathetic nerve activation in rat atria and its dependence on calcium but not CAM kinase II and protein kinases A or C
Authors: Kotsonis P. , Binko J. , Majewski H.
Published: July 2012

The biosynthesis of noradrenaline following sympathetic nerve activation was investigated in rat atria. In particular the time course of noradrenaline synthesis changes, the relationship of changes in synthesis to transmitter release and the possible roles of second messengers and protein kinases were examined.

Rat atria incubated with the precursor [3H]‐tyrosine synthesized [3H]‐noradrenaline. Synthesis was enhanced following pulsatile electrical field stimulation (3 Hz for 5 min) with the bulk of the increase occurring in the first 45 min after the commencement of electrical stimulation. In separate experiments rat atria were pre‐incubated with [3H]‐noradrenaline and the radioactive outflow in response to electrical field stimulation (3 Hz for 5 min) was taken as an index of noradrenaline release.

Stimulation‐induced (S‐I) noradrenaline synthesis was significantly correlated to S‐I noradrenaline release for a variety of procedures which modulate noradrenaline release by mechanisms altering Ca2+ entry into the neurone (r2 = 0.99): those which decreased release: tetrodotoxin (0.3 μm), Ca2+‐free medium, lowering the frequency of nerve activation to 1 Hz, and those which increased release, tetraethylammonium (0.3 mM), phentolamine (1 μm) and the combination of phentolamine (1 μm) and adenosine (10 μm). On the strength of this relationship we suggest that Ca2+ entry is a determining factor in S‐I synthesis changes rather than the amount of noradrenaline released. Indeed the reduction in noradrenaline release with the calmodulin‐dependent protein (CAM) kinase II inhibitor KN‐62 (10 μm) which acts subsequent to Ca2+ entry, did not affect S‐I synthesis.

The cell permeable cyclic AMP analogue, 8‐bromoadenosine 3′, 5′‐monophosphate (BrcAMP, 90 and 270 μm), dose‐dependently increased basal [3H]‐noradrenaline synthesis in unstimulated rat atria. This effect was antagonized by the selective protein kinase A (PKA) antagonist, Rp‐8‐chloroadenosine 3′, 5′‐cyclic monophosphorothioate (RClcAMPS, 300 μm), suggesting that PKA activation enhances basal noradrenaline biosynthesis in sympathetic nerve terminals.

The protein kinase inhibitors, KN‐62 (CAM kinase II, 10 μm), RClcAMPS (PKA, 300 μm), polymyxin B (protein kinase C (PKC), 21 μm) and staurosporine (PKC, PKA and CAM kinase II, 0.1 μm) did not affect S‐I synthesis, although KN‐62, polymyxin B and staurosporine decreased S‐I release. We conclude that S‐I synthesis is triggered by Ca2+ entering the neurone but that the signalling pathway does not involve classical protein kinases and appears distinct from the steps involved in transmitter release.
The inhibitory effects of α2‐adrenoceptor agonists on gastrointestinal transit during croton oil‐induced intestinal inflammation
Authors: Pol Olga , Valle Lluis , Ferrer Isidre , Puig Margarita M.
Published: July 2012

The peripheral effects of α2‐adrenoceptor agonists were investigated in a model of intestinal inflammation induced by intragastric administration of croton oil (CO). Our hypothesis was that inflammation would ‘sensitize’ adrenoceptors in peripheral and/or central terminals of myenteric and submucous plexus neurones, and enhance systemic effects of α2‐adrenoceptor agonists.

Male swiss CD‐1 mice, received intragastrically CO (0.05 ml), castor oil (CA, 0.1 ml) or saline (SS) 3 h before the study: gastrointestinal transit (GIT) was evaluated 20 min afterwards with a charcoal meal. The presence of inflammation was assessed by electron microscopy.

The intragastric administration of CA or CO caused an increase in GIT and weight loss, but only CO induced an inflammatory response. Both clonidine (imidazoline1/α2‐agonist) and UK‐14304 (α2‐agonist) produced dose‐related inhibitions of GIT in all groups. During inflammatory diarrhoea (CO), potencies of systemic (s.c.) clonidine and UK‐14304 were significantly increased 3.5 and 2.1 times, respectively, while potencies remained unaltered in the presence of diarrhoea without inflammation (CA). The effects were reversed by administration (s.c.) of receptor‐specific adrenoceptor antagonists, but not by naloxone.

Clonidine was 8.3 (SS) and 2.8 (CO) times more potent when administered intracerebroventricularly (i.c.v.), than when administered s.c. Inflammation of the gut did not alter the potency of i.c.v. clonidine, demonstrating that enhanced effects of s.c. clonidine are mediated by peripheral receptors. During inflammation, i.c.v. efaroxan did not antagonize low doses of s.c. clonidine (ED20 and ED50s), but partially reversed ED80s, further supporting the peripheral effects of the agonists in CO treated animals.

The results demonstrate that inflammation of the gut enhances the potency of α2‐adrenoceptor agonists by a peripheral mechanism. The results also suggest that the inflammatory response induces an up‐regulation or sensitization of α‐adrenoceptors and/or imidazoline receptors.
Associations between infections and clinical outcome parameters in status epilepticus: A retrospective 5‐year cohort study
Authors: Sutter Raoul , Tschudin‐Sutter Sarah , Grize Leticia , Fuhr Peter , Bonten Marc J. M. , Widmer Andreas F. , Marsch Stephan , Rüegg Stephan
Published: July 2012

Purpose:  Status epilepticus (SE) represents a life‐threatening condition, requiring pharmacologic therapy and neurointensive care. Infectious complications in SE are suspected to be frequent and worsen outcome. However, little is known about their incidence during SE and their impact on course and outcome. The aim of this study was to determine the incidence and time of onset of infections during SE, as well as their association with particular SE courses, length of hospitalization, intensive care unit (ICU) stay, and outcome.

Methods:  All consecutive ICU patients hospitalized due to SE from 2005 to 2009 at the University Hospital Basel were included. Electroencephalography (EEG) recordings and microbiologic data were extracted from two prospectively established databases. Length of SE, ICU, and hospital stay; development of refractory status epilepticus (RSE); and destinations at discharge or death were assessed by comprehensive medical chart review.

Key Findings:  Of 160 patients, 23% had infections during SE. Of those, 94% were respiratory tract infections, 29% were ventilator‐associated pneumonias. Patients with infections during SE had longer SE duration (p < 0.0001), longer ICU stay (p = 0.0041), higher risk of RSE (odds ratio [OR] 4.8, p = 0.0002), and higher mortality (OR 5.2, p = 0.0003) than those without infectious complications. Infections during the first 3 days after SE onset were significantly associated with longer SE duration, higher rate of RSE, and higher mortality compared to infections detected before SE.

Significance:  Infections during SE are frequent and associated with higher mortality, prolonged ICU stay, and higher rates of RSE. Further trials are needed to provide evidence of a causative relation between infections and outcomes of SE, followed by investigations on underlying mechanisms and preventive strategies.
MORPHOLOGICAL STUDIES OF SOME MARINE MASTOGLOIA (BACILLARIOPHYCEAE) BELONGING TO SECTION SULCATAE, INCLUDING THE DESCRIPTION OF NEW SPECIES
Authors: Pennesi Chiara , Poulin Michel , De Stefano Mario , Romagnoli Tiziana , Totti Cecilia
Published: July 2012

Epiphytic diatoms on seagrass and seaweed were collected from tropical (e.g., Siladen Island, Celebes Sea, Indonesia and Phú Bài, China Sea, Vietnam), subtropical (e.g., Sharm el‐Sheikh, Red Sea, Egypt), and temperate regions (e.g., Patmos Island, Greece) in 2000, 2005, and 2006. Eight species of Mastogloia, belonging to the section Sulcatae, are described mainly through scanning electron microscopy, including two new species to science, M. oculoides and M. sergiana. These species show a differently shaped median depression on the external valve face between the raphe‐sternum and the valve margin. Moreover, they lack a developed conopeum or pseudoconopeum, which covers the median depression in other species of the section Sulcatae. This study gives new insights on the ultrastructure of the Mastogloia's valves and provides an update of their current geographical distribution.
Technological Growth and Asset Pricing
Authors: GÂRLEANU NICOLAE , PANAGEAS STAVROS , YU JIANFENG
Published: July 2012

We study the asset‐pricing implications of technological growth in a model with “small,” disembodied productivity shocks and “large,” infrequent technological innovations, which are embodied into new capital vintages. The technological‐adoption process leads to endogenous cycles in output and asset valuations. This process can help explain stylized asset‐valuation patterns around major technological innovations. More importantly, it can help provide a unified, investment‐based theory for numerous well‐documented facts related to excess‐return predictability. To illustrate the distinguishing features of our theory, we highlight novel implications pertaining to the joint time‐series properties of consumption and excess returns.
Mutual Fund Trading Pressure: Firm‐Level Stock Price Impact and Timing of SEOs
Authors: KHAN MOZAFFAR , KOGAN LEONID , SERAFEIM GEORGE
Published: July 2012

We use price pressure resulting from purchases by mutual funds with large capital inflows to identify overvalued equity. This is a relatively exogenous overvaluation indicator as it is associated with who is buying—buyers with excess liquidity—rather than what is being purchased. We document substantial stock price impact associated with purchases by high‐inflow mutual funds, and find the probability of a seasoned equity offering (SEO), insider sales, and the probability of a stock‐based acquisition increase significantly in the four quarters following the mutual fund buying pressure. These results provide new evidence that firm managers are able to identify and exploit overvalued equity.
Real Options, Volatility, and Stock Returns
Authors: GRULLON GUSTAVO , LYANDRES EVGENY , ZHDANOV ALEXEI
Published: July 2012

We provide evidence that the positive relation between firm‐level stock returns and firm‐level return volatility is due to firms’ real options. Consistent with real option theory, we find that the positive volatility‐return relation is much stronger for firms with more real options and that the sensitivity of firm value to changes in volatility declines significantly after firms exercise their real options. We reconcile the evidence at the aggregate and firm levels by showing that the negative relation at the aggregate level may be due to aggregate market conditions that simultaneously affect both market returns and return volatility.
Intra‐Atrial Conduction Block Mimicking Atrioventricular Nodal Block After Multiple Catheter Ablation Procedures for Atrial Tachycardia in a Patient with Cardiomyopathy
Authors: CHUGH AMAN , YOKOKAWA MIKI , BAMAN TIMIR , BOGUN FRANK , WU AUDREY
Published: July 2012

Intra‐Atrial Conduction Block. A 42‐year‐old woman with a history of cardiomyopathy and multiple ablation procedures for atrial tachycardia developed intra‐atrial conduction block that mimicked atrioventricular (AV) nodal block during radiofrequency ablation at the cavotricuspid isthmus. She was treated with atrial pacing (from the coronary sinus), which overcame intra‐atrial conduction block and resulted in AV nodal conduction. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1258–1261, November 2012)
Effect of Y‐α‐Sialon Seeding and Holding Time on the Formation of Elongated (Ca,Dy)‐α‐Sialon Crystals Prepared via Carbothermal Reduction and Nitridation
Authors: Huang Juntong , Zhou Heping , Huang Zhaohui , Liu Guanghua , Fang Minghao , Liu Yan'gai
Published: July 2012

Single‐phase (Ca,Dy)‐α‐Sialon with elongated crystals and high aspect ratios was prepared at 1700°C by carbothermal reduction and nitridation (CRN) with Y‐α‐Sialon seed crystals. Effects of Y‐α‐Sialon seeding and holding time on the phase assemblage and crystal morphology of CRN products were discussed. The results showed that adding seed crystals and prolonging holding time could facilitate not only phase transformation, but also crystal refinement. Moreover, they resulted in the increase of the aspect ratios of α‐Sialon crystals, due to the decreasing range in the crystal width exceeding that in the length. In addition, a highly unusual phenomenon of crystal size reduction during reaction was observed in the seeded samples with the holding time extending from 2 to 4 h. Crystallization from liquid phase and growth followed by nucleation based on the surface of existing large crystals were the growth modes of elongated α‐Sialon crystals.
Antibacterial effects of blackberry extract target periodontopathogens
Authors: González O. A. , Escamilla C. , Danaher R. J. , Dai J. , Ebersole J. L. , Mumper R. J. , Miller C. S.
Published: July 2012

Background and Objective:  Antimicrobial agents provide valuable adjunctive therapy for the prevention and the control of oral diseases. Limitations in their prolonged use have stimulated the search for new, naturally occurring agents with more specific activity and fewer adverse effects. Here we sought to determine the antibacterial properties of blackberry extract (BBE) in vitro against oral bacterial commensals and periodontopathogens.

Material and Methods:  The effects of whole and fractionated BBE on the metabolism of 10 different oral bacteria were evaluated using the colorimetric water‐soluble tetrazolium‐1 assay. The bactericidal effects of whole BBE against Fusobacterium nucleatum were determined by quantitating the numbers of colony‐forming units (CFUs). Cytotoxicity was determined in oral epithelial (OKF6) cells.

Results:  BBE at 350–1400 μg/mL reduced the metabolic activity of Porphyromonas gingivalis, F. nucleatum and Streptococcus mutans. The reduced metabolic activity observed for F. nucleatum corresponded to a reduction in the numbers of CFUs following exposure to BBE for as little as 1 h, indicative of its bactericidal properties. An anthocyanin‐enriched fraction of BBE reduced the metabolic activity of F. nucleatum, but not of P. gingivalis or S. mutans, suggesting the contribution of species‐specific agents in the whole BBE. Oral epithelial cell viability was not reduced following  exposure to whole BBE (2.24–1400 μg/mL) for ≤ 6 h.

Conclusion:  BBE alters the metabolic activity of oral periodontopathogens while demonstrating a minimal effect on commensals. The specific antibacterial properties of BBE shown in this study, along with its previously demonstrated anti‐inflammatory and antiviral properties, make this natural extract a promising target as an adjunct for prevention and/or complementary therapy of periodontal infections.
A pharmacokinetic study of a topical anesthetic (EMLA®) in mouse soft tissue laceration
Authors: Al‐Musawi Alaa , Matar Kamal , Kombian Samuel B. , Andersson Lars
Published: July 2012

The use of topical anesthesia instead of injection of local anesthetics for managing soft tissue lacerations in the emergency situations may be a relief for both patients and surgeons. Topical anesthesia in the form of a cream eutectic mixture of local anesthetics (EMLA®) containing 2.5% lidocaine and 2.5% prilocaine has been reported as an efficient anesthetic on skin before venipuncture anesthesia and as an alternative to injection anesthesia in some minor surgery situations. The aim of this study was to compare the pharmacokinetics of EMLA® when applied in a laceration with topical skin application in the mouse. A total of 120 Albino Laboratory‐bred strain mouse (BALB‐c) male mice were divided into three groups with regard to application mode of EMLA®. Group A: with laceration, 48 mice; Group B: on intact shaved skin, 48 mice; Group C: control group (24 mice) with same procedures but without application of EMLA®. Blood levels were collected at 0, 10, 20, 30, 45, 60, 75, and 90 min post‐EMLA® application. Plasma sample analysis was carried out by employing liquid chromatography coupled with tandem mass spectrometric (LC‐MS/MS) method, and the pharmacokinetic analysis of the mouse plasma samples was estimated by standard non‐compartmental methods. The pharmacokinetic parameters of lidocaine and prilocaine were significantly altered following EMLA® application to lacerated mouse skin in contrast to intact skin. The absorption of lidocaine and prilocaine was rapid following application of EMLA® to lacerated and intact mouse skin. Maximum drug plasma concentration (Cmax) and area under the drug plasma concentration–time curve (AUC) values of lidocaine were significantly increased by 448.6% and 161.5%, respectively, following application of EMLA to lacerated mouse skin in comparison with intact mouse skin. Similarly, prilocaine's Cmax and AUC values were also increased by 384% and 265.7%, respectively, following EMLA application to lacerated mouse skin, in contrast to intact skin. Further pharmacokinetic studies on different carriers of lidocaine/prilocaine are warranted before any firm conclusions for the clinic can be drawn.
Effects of exposure to plant‐derived odorants on behavior and the concentration of stress‐related hormones in steers isolated under a novel environment
Authors: SUTOH Madoka , ITO Shuichi , KASUYA Etsuko , YAYOU Ken‐ichi
Published: July 2012

This study was conducted to investigate physiological and behavioral effects of the exposure to plant‐derived odorants in Holstein steers (8 month of age) under the acute stress of social isolation in a novel environment. Each steer was tethered in a new room alone and exposed to one of three odorants: a mixture of equal amounts of trans‐2‐hexenal and cis‐3‐hexenol (green odor, GO; n = 5), essential oil of grapefruits (EOG; n = 5) and solvent (SOL; n = 6). Behaviors were recorded and blood samples were taken at intervals of 10–15 min for 6 h. Compared with SOL, exposure to GO or EOG decreased the frequency of vocalization (P < 0.05), shortened the latency period before the onset of rumination (P < 0.05) and increased the duration of rumination (P < 0.05). Plasma cortisol concentrations in steers exposed to plant‐derived odorants (GO and EOG) during 90–130 min from commencement of sampling were significantly lower (P < 0.05) compared with SOL. These results suggest that appeasing effects of plant‐derived odorants on behavioral and physiological stress responses previously reported in laboratory rodents could be also be expected in steers.
POTENTIAL APPLICATION OF AN ANTI‐AEROMONAS BACTERIOCIN OF LACTOCOCCUS LACTIS SSP. LACTIS IN THE PRESERVATION OF VEGETABLE SALAD
Authors: KUMAR MUKESH , JAIN ALOK KUMAR , GHOSH MOUSHUMI , GANGULI ABHIJIT
Published: July 2012

The potential use of bacteriocins as natural food preservative has a wide range of applications in food industry, but the range is restricted mostly up to gram‐positive microorganism. In our work, a Lactococcus lactis ssp. lactis HKT‐9 strain isolated from hukuti maas produced a bacteriocin active against a variety of gram‐positive as well as gram‐negative foodborne pathogens but specificity toward Aeromonas spp. Partially purified bacteriocin revealed that the peptide was thermoresistant (15 min at 121C), active at acidic to alkaline pH between pH 2.0 and 10.0. Its molecular weight was approximately 2.5 kDa and shared the properties of class II bacteriocin family. Furthermore, the gene cluster encoding for bacteriocin produced by L. lactis ssp. lactis HKT‐9 showed 100% homology with the operon encoding pediocin PA‐1(class IIa bacteriocin). Among detergents, sodium dodecyl sulfate, Tween 80 and Tween 20 enhanced bacteriocin activity. Enzymes like α‐amylase; DNase and RNase showed slightly increased bacteriocin activity. Its mode of action was bactericidal against Aeromonas hydrophila American type culture collection 7966. Addition of crude bacteriocin HKT‐9 at concentration of 100 μg/mL to artificially contaminated vegetables inhibited the growth of A. hydrophlia up to 7 log cfu/mL within 24 h for at least 10 days, whereas reduction of 6 log cfu/mL was observed for Staphylococcus aureus.

Practical Application

Bacteriocins are ribosomally synthesized polypeptides possessing bacteriocidal activity that are rapidly digested by proteases in the human digestive tract. They are a heterogenous group characteristically selected for evaluation and use as specific antagonists against problematic bacteria. With the emergence of antibiotic‐resistant pathogenic bacteria, the possibility of bacteriocins as supplements or replacements for antibiotics for therapeutic use is also being considered; however, their effectiveness in foods can become limited for various reasons, and cost remains an issue impeding broader use of bacteriocins as food additives. Of all the antimicrobial peptides, very few have been used as preservatives in the food industry and/or as antibiotic substances in medicine. In the present study, effectiveness of an anti‐aeromonas bacteriocin of Lactococcus lactis ssp. lactis was studied for the preservation of vegetable salad under in vitro conditions.
Delphinid whistle production and call matching during playback of simulated military sonar
Authors: DeRuiter Stacy L. , Boyd Ian L. , Claridge Diane E. , Clark Christopher W. , Gagnon Chuck , Southall Brandon L. , Tyack Peter L.
Published: July 2012

Abstract

In 2007 and 2008, controlled exposure experiments were performed in the Bahamas to study behavioral responses to simulated mid‐frequency active sonar (MFA) by three groups of odontocetes: false killer whales, Pseudorca crassidens; short‐finned pilot whales, Globicephala macrorhynchus; and melon‐headed whales, Peponocephala electra. An individual in each group was tagged with a Dtag to record acoustic and movement data. During exposures, some individuals produced whistles that seemed similar to the experimental MFA stimulus. Statistical tests were thus applied to investigate whistle‐MFA similarity and the relationship between whistle production rate and MFA reception time. For the false killer whale group, overall whistle rate and production rate of the most MFA‐like whistles decreased with time since last MFA reception. Despite quite low whistle rates overall by the melon‐headed whales, statistical results indicated minor transient silencing after each signal reception. There were no apparent relationships between pilot whale whistle rates and MFA sounds within the exposure period. This variability of responses suggests that changes in whistle production in response to acoustic stimuli depend not only on species and sound source, but also on the social, behavioral, or environmental contexts of exposure.
Browsed twig environmental DNA: diagnostic PCR to identify ungulate species
Authors: NICHOLS RUTH V. , KÖNIGSSON HELENA , DANELL KJELL , SPONG GÖRAN
Published: July 2012

Ungulate browsing can have a strong effect on ecological processes by affecting plant community structure and composition, with cascading effects on nutrient cycling and animal communities. However, in the absence of direct observations of foraging, species‐specific foraging behaviours are difficult to quantify. We therefore know relatively little about foraging competition and species‐specific browsing patterns in systems with several browsers. However, during browsing, a small amount of saliva containing buccal cells is deposited at the bite site, providing a source of environmental DNA (eDNA) that can be used for species identification. Here, we describe extraction and PCR protocols for a browser species diagnostic kit. Species‐specific primers for mitochondrial DNA were optimized and validated using twigs browsed by captive animals. A time series showed that about 50% of the samples will amplify up to 12 weeks after the browsing event and that some samples amplify up to 24 weeks after browsing (12.5%). Applied to samples of natural browsing from an area where moose (Alces alces), roe deer (Capreolus capreolus), fallow deer (Cervus dama) and red deer (Cervus elaphus) are sympatric, amplification success reached 75%. This method promises to greatly improve our understanding of multispecies browsing systems without the need for direct observations.
Resting Heart Rate and Outcomes in Patients with Cardiovascular Disease: Where Do We Currently Stand?
Authors: Menown Ian B. A. , Davies Simon , Gupta Sandeep , Kalra Paul R. , Lang Chim C. , Morley Chris , Padmanabhan Sandosh
Published: July 2012

Background

Data from large epidemiological studies suggest that elevated heart rate is independently associated with cardiovascular and all‐cause mortality in patients with hypertension and in those with established cardiovascular disease. Clinical trial findings also suggest that the favorable effects of beta‐blockers and other heart rate–lowering agents in patients with acute myocardial infarction and congestive heart failure may be, at least in part, due to their heart rate–lowering effects. Contemporary clinical outcome prediction models such as the Global Registry of Acute Coronary Events (GRACE) score include admission heart rate as an independent risk factor.

Aims

This article critically reviews the key epidemiology concerning heart rate and cardiovascular risk, potential mechanisms through which an elevated resting heart rate may be disadvantageous and evaluates clinical trial outcomes associated with pharmacological reduction in resting heart rate.

Conclusions

Prospective randomised data from patients with significant coronary heart disease or heart failure suggest that intervention to reduce heart rate in those with a resting heart rate >70 bpm may reduce cardiovascular risk. Given the established observational data and randomised trial evidence, it now appears appropriate to include reduction of elevated resting heart rate by lifestyle +/− pharmacological therapy as part of a secondary prevention strategy in patients with cardiovascular disease.
Consumer behaviour towards counterfeit drugs in a developing country
Authors: Alfadl Abubakr A. , Ibrahim Mohamed Izham M. , Hassali Mohamed A.
Published: July 2012

Introduction

Availability of counterfeit drugs is increasing, especially in developing countries. This fact makes it critical to develop new measures that can help to combat this problem.

Objectives

This study was designed to examine the influence of certain factors on consumers' behaviour regarding counterfeit drugs. Specifically, this study investigates consumers' intention to purchase counterfeit drugs based on their attitude towards the purchase of counterfeit drugs, subjective norm and motivation.

Method

This study was conducted in a resource limited setting context. A face-to-face structured interview survey methodology was employed to collect data from 1003 subjects. Data were analysed by maximum likelihood estimation procedures using structural equation modelling.

Key findings

Out of a total of 11 proposed hypotheses, only four were significant as expected. All hypotheses related to factors affecting attitude were found to be non-significant and, consequently, attitude towards purchase intention was also found to be non-significant.

Conclusion

The model, which was based on past research and the authors' theoretical considerations, was confirmed. Moreover, using the theory of planned behaviour provided strong contributions towards explaining the demand for counterfeit drugs. This study is among the few, and may indeed be the first, that examines an African country drugs market and provides information and knowledge highly demanded by marketing managers and public health policymakers. It provides an in-depth understanding of Sudanese consumers that can be used in designing more efficient anti-counterfeiting strategies in developing countries.
Proton therapy dose distribution comparison between Monte Carlo and a treatment planning system for pediatric patients with ependymomaa)
Authors: Jia Yingcui , Beltran Chris , Indelicato Daniel J. , Flampouri Stella , Li Zuofeng , Merchant Thomas E.
Published: July 2012

Purpose

: Compare dose distributions for pediatric patients with ependymoma calculated using a Monte Carlo (MC) system and a clinical treatment planning system (TPS).

Methods

: Plans from ten pediatric patients with ependymoma treated using double scatter proton therapy were exported from the TPS and calculated in our MC system. A field by field comparison of the distal edge (80% and 20%), distal fall off (80% to 20%), field width (50% to 50%), and penumbra (80% to 20%) were examined. In addition, the target dose for the full plan was compared.

Results

: For the 32 fields from the 10 patients, the average differences of distal edge at 80% and 20% on central axis between MC and TPS are −1.9 ± 1.7 mm (p < 0.001) and −0.6 ± 2.3 mm (p = 0.13), respectively. Excluding the fields that ranged out in bone or an air cavity, the 80% difference was −0.9 ± 1.7 mm (p = 0.09). The negative value indicates that MC was on average shallower than TPS. The average difference of the 63 field widths of the 10 patients is −0.7 ± 1.0 mm (p < 0.001), negative indicating on average the MC had a smaller field width. On average, the difference in the penumbra was 2.3 ± 2.1 mm (p < 0.001). The average of the mean clinical target volume dose differences is −1.8% (p = 0.001), negative indicating a lower dose for MC.

Conclusions

: Overall, the MC system and TPS gave similar results for field width, the 20% distal edge, and the target coverage. For the 80% distal edge and lateral penumbra, there was slight disagreement; however, the difference was less than 2 mm and occurred primarily in highly heterogeneous areas. These differences highlight that the TPS dose calculation cannot be automatically regarded as correct.
Performance evaluation of x‐ray differential phase contrast computed tomography (PCT) with respect to medical imaging
Authors: Raupach Rainer , Flohr Thomas
Published: July 2012

Purpose:

To evaluate the maximum performance gain that can theoretically be achieved with differential phase contrast computed tomography (PCT) compared with absorption‐based CT, applied toin vivo medical imaging.

Methods:

We develop a mathematical framework for analyzing the performance of PCT relative to CT under ideal conditions. We validate our model by interpreting the results of published PCT experiments. Finally, we utilize our framework to evaluate the relative performance of PCT versus CT forin vivo medical imaging of the human body, investigating several clinically relevant material contrasts.

Results

: We show that the performance of PCT relative to CT depends on the ratio of phase contrast and absorption contrast of the examined materials and increases with increasing effective coherence length and increasing spatial resolution. The introduced effective coherence length characterizes an experimental PCT setup; it comprises coherence of the beam as well as properties of the x‐ray interferometer. Whole body medical CT will not benefit from phase‐contrast imaging, because the higher phase contrast is overcompensated by the low coherence lengths of PCT setups with low‐brilliance sources, and by limited spatial resolution. The relative performance of PCT, which is inferior to CT for all examined material contrasts at the resolution level of today's medical CT, can be improved by increasing spatial resolution at the expense of increased patient dose. At the break‐even point of equal performance for PCT and CT, a radiation dose at least 1 order of magnitude higher than today is required. Mammographic CT already operates at higher spatial resolution and may benefit from PCT for some applications in terms of reduced patient dose at equal image quality.

Conclusions:

Phase‐contrast imaging utilizing low‐brilliance x‐ray sources has limited potential for an application in routine whole body CT. Breast CT, however, may benefit from phase‐contrast imaging. These conclusions are due to fundamental arguments and independent of whether technical issues (quality of gratings, etc.) can be solved. PCT will only be suitable forin vivo medical imaging if x‐ray sources with much better spatial coherence are routinely available.
Tracheostomy in children admitted to paediatric intensive care: Table 1
Authors: Wood Dora , McShane Philip , Davis Peter
Published: July 2012

Purpose

Tracheostomy is a common intervention for adults admitted to intensive care; many are performed early and most are percutaneous. Our study aimed to elucidate current practice and indications for children in the UK admitted to paediatric intensive care and undergoing tracheostomy.

Design

A questionnaire covering unit guidelines, practice, and the advantages and disadvantages of tracheostomy was sent to all UK paediatric intensive care units (PICUs) participating in the Paediatric Intensive Care Audit Network (PICANet). These results were combined with data from PICANet on all children in the UK reported to have had a tracheostomy performed during a PICU admission between 2005 and 2009 inclusive.

Results

Over 5 years, 1613 children had tracheostomies performed during their PICU admission (2.05% of all admissions). The death rate was 5.58% with tracheostomy versus 4.72% overall, but differences were not significant when risk-adjusted using the Paediatric Index of Mortality 2 (PIM2). All 29 units participating in PICANet responded to the survey. Prolonged invasive ventilation was an indication for tracheostomy in 25/29 units, but the definition varied between 14 and 90 days, and most respondents considered timing on an individual basis. Children undergoing tracheostomy during PICU admission account for 9% of PICU bed days in the UK.

Conclusions

In contrast with current adult UK practice, tracheostomy for children admitted to intensive care is infrequent, performed late following admission and usually surgical. Practice varies significantly. The death rate for children having a tracheostomy performed was not significantly higher than for children admitted to PICU who did not undergo tracheostomy.
Association between socioeconomic status and self-reported diabetes in India: a cross-sectional multilevel analysis
Authors: Corsi Daniel J , Subramanian S V
Published: July 2012

Objectives

To quantify the association between socioeconomic status (SES) and type 2 diabetes in India.

Design

Nationally representative cross-sectional household survey.

Setting

Urban and rural areas across 29 states in India.

Participants

168 135 survey respondents aged 18–49 years (women) and 18–54 years (men).

Primary outcome measure

Self-reported diabetes status.

Results

Markers of SES were social caste, household wealth and education. The overall prevalence of self-reported diabetes was 1.5%; this increased to 1.9% and 2.5% for those with the highest levels of education and household wealth, respectively. In multilevel logistic regression models (adjusted for age, gender, religion, marital status and place of residence), education (OR 1.87 for higher education vs no education) and household wealth (OR 4.04 for richest quintile vs poorest) were positively related to self-reported diabetes (p<0.0001). In a fully adjusted model including all socioeconomic variables and body mass index, household wealth emerged as positive and statistically significant with an OR for self-reported diabetes of 2.58 (95% credible interval (CrI): 1.99 to 3.40) for the richest quintile of household wealth versus the poorest. Nationally in India, a one-quintile increase in household wealth was associated with an OR of 1.31 (95% CrI 1.20 to 1.42) for self-reported diabetes. This association was consistent across states with the relationship found to be positive in 97% of states (28 of 29) and statistically significant in 69% (20 of 29 states).

Conclusions

The authors found that the highest SES groups in India appear to be at greatest risk for type 2 diabetes. This raises important policy implications for addressing the disease burdens among the poor versus those among the non-poor in the context of India, where >40% of the population is living in poverty.
The evidence underpinning sports performance products: a systematic assessment
Authors: Heneghan Carl , Howick Jeremy , O'Neill Braden , Gill Peter J , Lasserson Daniel S , Cohen Deborah , Davis Ruth , Ward Alison , Smith Adam , Jones Greg , Thompson Matthew
Published: July 2012

Background

To assess the extent and nature of claims regarding improved sports performance made by advertisers for a broad range of sports-related products, and the quality of the evidence on which these claims are based.

Methods

The authors analysed magazine adverts and associated websites of a broad range of sports products. The authors searched for references supporting the performance and/or recovery claims of these products. The authors critically appraised the methods in the retrieved references by assessing the level of evidence and the risk of bias. The authors also collected information on the included participants, adverse events, study limitations, the primary outcome of interest and whether the intervention had been retested.

Results

The authors viewed 1035 web pages and identified 431 performance-enhancing claims for 104 different products. The authors found 146 references that underpinned these claims. More than half (52.8%) of the websites that made performance claims did not provide any references, and the authors were unable to perform critical appraisal for approximately half (72/146) of the identified references. None of the references referred to systematic reviews (level 1 evidence). Of the critically appraised studies, 84% were judged to be at high risk of bias. Randomisation was used in just over half of the studies (58.1%), allocation concealment was only clear in five (6.8%) studies; and blinding of the investigators, outcome assessors or participants was only clearly reported as used in 20 (27.0%) studies. Only three of the 74 (2.7%) studies were judged to be of high quality and at low risk of bias.

Conclusions

The current evidence is not of sufficient quality to inform the public about the benefits and harms of sports products. There is a need to improve the quality and reporting of research, a move towards using systematic review evidence to inform decisions.
Stromal invasion and micropapillary pattern in 212 consecutive surgically resected stage I lung adenocarcinomas: histopathological categories for prognosis prediction
Authors: Yeh Yi-Chen , Wu Yu-Chung , Chen Cheng-Yu , Wang Liang-Shun , Hsu Wen-Hu , Chou Teh-Ying
Published: July 2012

Background and Aim

It is of importance to search for prognostic indicators supplementing the tumour–node–metastasis stage for surgically resected early-stage lung adenocarcinomas. The roles of stromal invasion and micropapillary pattern in categorising histopathology and predicting the prognosis of stage I lung adenocarcinomas are explored.

Methods

We retrospectively examined 212 consecutive surgically resected stage I lung adenocarcinomas to propose a new histopathology-based categorical classification. Category A tumours have pure lepidic growth pattern without stromal invasion (ie, adenocarcinoma in situ). Stromal invasion in the form of central fibrotic focus is absent in category B tumours and present in category C tumours. Category B is subclassified into B1, which has areas of lepidic growth, and B2, which does not. Category C is subclassified into C1, which has invasive tumour cells in the periphery of central fibrotic focus, and C2, which has invasive tumour cells in the centre of central fibrotic focus. Based on the absence or presence of micropapillary pattern, the C2 tumours are further subclassified into C2a and C2b, respectively.

Results

The 5-year recurrence-free probabilities for categories B1 (17 cases), B2 (10 cases), C1 (nine cases), C2a (114 cases) and C2b (62 cases) are 100%, 78.8%, 100%, 67.5% and 53.1%, respectively (p<0.001).

Conclusions

Based on stromal invasion and micropapillary pattern, the histopathological categorical classification proposed here provides a concise and precise scheme for outcome prediction in early-stage lung adenocarcinomas.
The dimeric platelet collagen receptor GPVI-Fc reduces platelet adhesion to activated endothelium and preserves myocardial function after transient ischemia in mice
Authors: Schönberger Tanja , Ziegler Melanie , Borst Oliver , Konrad Ildiko , Nieswandt Bernhard , Massberg Steffen , Ochmann Carmen , Jürgens Tobias , Seizer Peter , Langer Harald , Münch Götz , Ungerer Martin , Preissner Klaus T. , Elvers Margitta , Gawaz Meinrad
Published: July 2012

Platelets play a critical role in the pathophysiology of reperfusion, sepsis, and cardiovascular diseases. In a multiple step process, they adhere to activated endothelium and release proinflammatory cytokines thereby promoting the inflammatory process. Glycoprotein VI (GPVI) is the major collagen receptor on the platelet surface and triggers platelet activation and primary hemostasis. Activation of GPVI leads to stable platelet adhesion and degranulation of platelet granules. However, GPVI is critically involved in platelet adhesion to activated endothelium without exposure of subendothelial matrix. Earlier studies show that the soluble GPVI-Fc binds to collagen and protects mice from atherosclerosis and decreases neointima proliferation after arterial injury. Here, we show for the first time that recombinant GPVI-Fc binds to activated endothelium mainly via vitronectin and prevents platelet/endothelial interaction. Administration of GPVI-Fc reduced infarct size and preserved cardiac function in a mouse model of myocardial infarction. This process was associated with reduced GPVI-induced platelet degranulation and release of proinflammatory cytokines in vitro and in vivo. Taken together, administration of GPVI-Fc offers a novel strategy to control platelet-mediated inflammation and to preserve myocardial function following myocardial infarction.
Differential regulation of sympathetic burst frequency and amplitude following acute hypoxia in humans
Authors: Steinback Craig D. , Kevin Shoemaker J.
Published: July 2012

Current evidence suggests that the persistent sympathetic nerve activity (SNA), commonly observed after exposure to hypoxia (HX), is mediated by chemoreceptor sensitization and or baroreflex resetting. Evidence in humans and animals suggests that these reflexes may independently regulate the frequency (gating) and amplitude (neuronal recruitment) of SNA bursts. In humans ( n = 7), we examined the regulation of SNA following acute isocapnic HX (5 min; end-tidal Po2 = 45 Torr) and euoxic hypercapnia (HC; 5 min; end-tidal Pco2 = +10 from baseline). HX increased SNA burst frequency (21 ± 7 to 28 ± 8 bursts/min, P < 0.05) and amplitude (99 ± 10 to 125 ± 19 au, P < 0.05) as did HC (14 ± 6 to 22 ± 10 bursts/min, P < 0.05 and 100 ± 12 to 133 ± 29 au, P < 0.05, respectively). Burst frequency (26 ± 7 bursts/min, P < 0.05), but not amplitude (97 ± 12 au), remained elevated 10 min post-HX. The change in burst amplitude (but not frequency) was significantly related to the measured change in ventilation ( r2 = 0.527, P < 0.001). Both frequency and amplitude decreased during recovery following HC. These data indicate the differential regulation of pattern and magnitude of sympathetic outflow in humans with sympathetic persistence following HX being specific to burst frequency and not amplitude.
Synchronized activation of sympathetic vasomotor, cardiac, and respiratory outputs by neurons in the midbrain colliculi
Authors: Iigaya Kamon , Müller-Ribeiro Flávia Camargos de Figueirêdo , Horiuchi Jouji , McDowall Lachlan M. , Nalivaiko Eugene , Fontes Marco A. P. , Dampney Roger A. L.
Published: July 2012

The superior and inferior colliculi are believed to generate immediate and highly coordinated defensive behavioral responses to threatening visual and auditory stimuli. Activation of neurons in the superior and inferior colliculi have been shown to evoke increases in cardiovascular and respiratory activity, which may be components of more generalized stereotyped behavioral responses. In this study, we examined the possibility that there are “command neurons” within the colliculi that can simultaneously drive sympathetic and respiratory outputs. In anesthetized rats, microinjections of bicuculline (a GABAAreceptor antagonist) into sites within a circumscribed region in the deep layers of the superior colliculus and in the central and external nuclei of the inferior colliculus evoked a response characterized by intense and highly synchronized bursts of renal sympathetic nerve activity (RSNA) and phrenic nerve activity (PNA). Each burst of RSNA had a duration of ∼300–400 ms and occurred slightly later (peak to peak latency of 41 ± 8 ms) than the corresponding burst of PNA. The bursts of RSNA and PNA were also accompanied by transient increases in arterial pressure and, in most cases, heart rate. Synchronized bursts of RSNA and PNA were also evoked after neuromuscular blockade, artificial ventilation, and vagotomy and so were not dependent on afferent feedback from the lungs. We propose that the synchronized sympathetic-respiratory responses are driven by a common population of neurons, which may normally be activated by an acute threatening stimulus.