bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceptions of distance education among nursing faculty members in North America
Authors: Mancuso Josephine M.
Published: April 2009

A strategy to increase access to nursing education, train nurses for practice, and prepare future nurse educators is distance education. Faculty member shortages are cited as the main reason for not accepting qualified applicants. Faculty members are the core of nursing education. In order to address nursing faculty members' concerns regarding distance education and to assist in faculty member recruitment, retention, growth, and development in order to improve and enhance the quality of distance education, one must answer the question: What are nursing faculty members' perceptions of distance education in nursing? Utilizing a number of databases to locate research specific to this topic, this article provides an integrative review of the nursing literature to ascertain the faculty members' perspective of distance education. The research was analyzed, findings summarized, and limitations mentioned. Utilizing a brief supplementary review of the literature, the implications, recommendations, and need for future research are discussed.
Latitudinal distribution of prokaryotic picoplankton populations in the Atlantic Ocean
Authors: Schattenhofer Martha , Fuchs Bernhard M. , Amann Rudolf , Zubkov Mikhail V. , Tarran Glen A. , Pernthaler Jakob
Published: April 2009

Members of the prokaryotic picoplankton are the main drivers of the biogeochemical cycles over large areas of the world's oceans. In order to ascertain changes in picoplankton composition in the euphotic and twilight zones at an ocean basin scale we determined the distribution of 11 marine bacterial and archaeal phyla in three different water layers along a transect across the Atlantic Ocean from South Africa (32.9°S) to the UK (46.4°N) during boreal spring. Depth profiles down to 500 m at 65 stations were analysed by catalysed reporter deposition fluorescence in situ hybridization (CARD‐FISH) and automated epifluorescence microscopy. There was no obvious overall difference in microbial community composition between the surface water layer and the deep chlorophyll maximum (DCM) layer. There were, however, significant differences between the two photic water layers and the mesopelagic zone. SAR11 (35 ± 9%) and Prochlorococcus (12 ± 8%) together dominated the surface waters, whereas SAR11 and Crenarchaeota of the marine group I formed equal proportions of the picoplankton community below the DCM (both ∼15%). However, due to their small cell sizes Crenarchaeota contributed distinctly less to total microbial biomass than SAR11 in this mesopelagic water layer. Bacteria from the uncultured Chloroflexi‐related clade SAR202 occurred preferentially below the DCM (4–6%). Distinct latitudinal distribution patterns were found both in the photic zone and in the mesopelagic waters: in the photic zone, SAR11 was more abundant in the Northern Atlantic Ocean (up to 45%) than in the Southern Atlantic gyre (∼25%), the biomass of Prochlorococcus peaked in the tropical Atlantic Ocean, and Bacteroidetes and Gammaproteobacteria bloomed in the nutrient‐rich northern temperate waters and in the Benguela upwelling. In mesopelagic waters, higher proportions of SAR202 were present in both central gyre regions, whereas Crenarchaeota were clearly more abundant in the upwelling regions and in higher latitudes. Other phylogenetic groups such as the Planctomycetes, marine group II Euryarchaeota and the uncultured clades SAR406, SAR324 and SAR86 rarely exceeded more than 5% of relative abundance.
Trends towards increased use of the laparoscopic approach in colorectal surgery
Authors: Lengyel J. , Morrison C. , Sagar P. M.
Published: April 2009

Aim  The aim of the study was to identify the trend towards laparoscopic resection in the practice of one surgeon and to determine whether the default approach to all colorectal procedures could be by means of minimally invasive techniques with an associated low rate of conversion.

Method  A prospective database of primary colorectal resections under the care of one colorectal surgeon collected between July 2003 and December 2008 was analysed to determine the trend in the use of the laparoscopic approach and the rate of conversion of an intention‐to‐treat policy for laparoscopic procedures. Patients with recurrent rectal or colonic malignancy were excluded from the study.

Results  A total of 598 patients underwent elective colorectal resection of which 371 (62%) were carried out laparoscopically with a rate of conversion of 3.2%. The proportion of all colorectal resections that were undertaken laparoscopically in the first 1 year was 26% (22/85) (no conversions). This proportion rose to 100% (127/127) in the fifth year of the study of which 4.0% were converted. The introduction of more complex procedures did not have an adverse effect on the trend towards more laparoscopic resections The commencement of a laparoscopic colorectal fellowship in 2006 was associated with a marked increase in the number of laparoscopic cases.

Conclusion  A conscious decision to make the laparoscopic approach the default for all colorectal resections can be achieved safely with a low conversion rate. This can be achieved within the context of training a ‘novice’ laparoscopic colorectal surgeon.
Labor‐Market Search, Financial Market Integration, and the Fiscal Multiplier
Authors: Çenesiz M. Alper , Pierdzioch Christian
Published: April 2009

We used a two‐country optimizing “new‐open‐economy macroeconomics” model to analyze the implications of financial market integration for the fiscal multiplier. The fiscal multiplier measures the accumulated effect of fiscal policy on output. Our model features a labor‐market friction in the form of labor‐market search. The conventional wisdom derived from the basic textbook version of the classic Mundell–Fleming model has been that financial market integration diminishes the fiscal multiplier. We show that labor‐market search implies that financial market integration should increase rather than decrease the fiscal multiplier.
Trade, Growth, and Environmental Quality*
Authors: Sirakaya Sibel , Turnovsky Stephen J. , Alemdar Nedim M.
Published: April 2009

This paper examines linkages between international trade, environmental degradation, and economic growth in a dynamic North–South trade game. Using a neoclassical production function subject to an endogenously improving technology, North produces manufactured goods by employing labor, capital, and a natural resource that it imports from South. South extracts the resource using raw labor, in the process generating local pollution. We study optimal regional policies in the presence of local pollution and technology spillovers from North to South under both non‐cooperative and cooperative modes of trade. Non‐cooperative trade is inefficient due to stock externalities. Cooperative trade policies are efficient and yet do not benefit North. Both regions gain from improved productivity in North and faster knowledge diffusion to South regardless of the trading regime.
The welfare politics of Charles Murray are alive and well in the UK
Authors: Prideaux Simon John
Published: April 2009

Prideaux SJ. The welfare politics of Charles Murray are alive and well in the UK Int J Soc Welfare 2010: 19: 293–302 © 2009 The Author(s), Journal compilation © 2009 Blackwell Publishing Ltd and the International Journal of Social Welfare.

This article takes a historical look at the ‘underclass’ debate that was prominently provoked and perpetuated in Britain by the American Charles Murray. It does so because the recent protestations about gun crime, welfare dependency and lone parenthood by David Cameron and the Conservative Party have not only echoed New Labour's New Deal logic, but have also reignited an argument that furiously raged in British policy debates during the 1980s and 1990s. Despite numerous criticisms and critics questioning Murray's selection of evidence, methodology and use of anecdotal vignettes, it is still apparent that the stereotypical assumptions about a section of British society who choose not to work, live a life of crime and produce inadequately socialised illegitimate children still persist. Consequently, the article revisits these arguments so that lessons from the past can now be brought to the fore and, hopefully, taken on board academically if not politically.
Juvenile bullous pemphigoid: the presentation and follow‐up of six cases
Authors: Gajic‐Veljic M , Nikolic M , Medenica L
Published: May 2009

Background  Juvenile bullous pemphigoid (JBP) is a very rare autoimmune blistering disease. Up to now, 81 cases have been published.

Objectives  To describe clinical, histopathological and immunopathological characteristics of our patients with JBP, their response to therapy and clinical course, and to show the rarity of JBP in our population.

Study design  Retrospective study of all patients with JBP diagnosed from 1983 to the end of 2007. The patients were followed from 6 months to 24 years.

Setting  An academic, teaching hospital – Pediatric Dermatology Unit of the Institute of Dermatovenereology, Clinical Center of Serbia, Belgrade.

Patients and methods  Six patients with JBP (4 girls and 2 boys) aged 2 to 17 years. The average age at onset of BP was 10 years. The diagnosis was confirmed by histopathological analysis and direct immunofluorescence test. The patients were treated with systemic and topical corticosteroids, and three patients received dapsone.

Results  The disease control was achieved after 2 weeks to 2.5 months of therapy. The treatment lasted from 2 weeks to 4.5 months, 1.8 months at the average. The period from the beginning of the disease to complete remission ranged from 1.5 month to 5 years, with a mean value of 14 months. In one boy, the parents interrupted the therapy, and the disease remitted spontaneously after 5 years.

Conclusion  According to our experience, JBP can spontaneously remit within 5 years. JBP has a relatively indolent course and may be a self‐limiting disease. The patients should not be over‐treated in order to avoid side‐effects of medication.
Fostering social engagement in Romanian children with communicative impairments: the experiences of newly trained practitioners of Intensive Interaction
Authors: Suzanne Zeedyk M. , Davies Cliff , Parry Sarah , Caldwell Phoebe
Published: April 2009

Accessible summary

This article describes the benefits of using an intervention technique called ‘Intensive Interaction’ to make connections with children who are socially withdrawn because of communicative impairments.

It summarises the accounts of 12 new trainees who used the technique while working as volunteers with abandoned, special needs children living in state care in Romania.

The comments of the volunteers showed that they could identify improvements in the children’s communicative abilities once they began to use Intensive Interaction. For example, the children looked at them more often, they were calmer, and they were more likely to turn the interactions into games.

The volunteers’ comments also made it clear that they felt closer to the children as a result of these changes in the interaction style.

These results are encouraging, because they suggest that practitioners can be trained in the basics of Intensive Interaction quickly and at a low cost, enabling them to reach children who often have trouble connecting to other people.

Within the special needs field, interactive interventions are gaining attention as a means of promoting social engagement for individuals with communicative impairments. The present paper examined the experiences of practitioners of one such approach, Intensive Interaction (II), by analysing written reflections provided by 12 newly trained practitioners. Their insights are particularly interesting because they were working in a voluntary capacity with a novel population: Romanian children living in state care, whose communicative impairments have been complicated by a history of neglect. A thematic analysis indicated that one hour’s training in II was sufficient for (i) enabling trainees to identify key changes in children’s engagement (e.g. increased attention to partner, decreased distress) and (ii) strengthening trainees’ sense of connection to the children. If such brief training sessions are effective in improving communicative interactions, this offers benefits to health and education service providers seeking to implement communicative intervention programmes. While interactive approaches have potential in all regions, they may be particularly valuable in countries such as Romania, which face monumental financial challenges in improving standards of childcare.
Stable–unstable flow of geothermal fluids in fractured rock
Authors: GRAF T. , THERRIEN R.
Published: May 2009

Density‐driven geothermal flow in 3‐D fractured rock is investigated and compared with density‐driven haline flow. For typical matrix and fracture hydraulic conductivities, haline flow tends to be unstable (convecting) while geothermal flow is stable (non‐convecting). Thermal diffusivity is generally three orders of magnitude larger than haline diffusivity and, as a result, large heat conduction diminishes growth of geothermal instabilities while low mass diffusion enables formation of unstable haline ‘fingering’ within fractures. A series of thermal flow simulations is presented to identify stable and unstable conditions for a wide range of hydraulic conductivities for matrix and fractures. The classic Rayleigh stability criterion can be applied to classify these simulations when fracture aperture is very small. However, the Rayleigh criterion is not applicable when the porous matrix hydraulic conductivity is very small, because stabilizing fracture–matrix heat conduction is independent of matrix hydraulic conductivity. In that case, the numerically estimated critical fracture conductivity is nine orders of magnitude larger than the theoretically calculated critical fracture conductivity based on Rayleigh theory. The numerical stability analysis presented here may be used as a guideline to predict if a geothermal system in 3‐D fractured rock is stable or unstable.
Relocation, reproduction and remaining alive in the orb‐web spider
Authors: Wherry T. , Elwood R. W.
Published: April 2009

When mortality is high, animals run a risk if they wait to accumulate resources for improved reproduction so they may trade‐off the time of reproduction with number and size of offspring. Animals may attempt to improve food acquisition by relocation, even in ‘sit and wait’ predators. We examine these factors in an isolated population of an orb‐web spider Zygiella x‐notata. The population was monitored for 200 days from first egg laying until all adults had died. Large females produced their first clutch earlier than did small females and there was a positive correlation between female size and the number and size of eggs produced. Many females, presumably without eggs, abandoned their web site and relocated their web position. This is presumed because female Zygiella typically guard their eggs. In total, c. 25% of females reproduced but those that relocated were less likely to do so, and if they did, they produced the clutch at a later date than those that remained. When the date of lay was controlled there was no effect of relocation on egg number but relocated females produced smaller eggs. The data are consistent with the idea that females in resource‐poor sites are more likely to relocate. Relocation seems to be a gamble to find a more productive site but one that achieves only a late clutch of small eggs and few achieve that.
The molecular chaperone Hsc70 interacts with the vesicular monoamine transporter‐2
Authors: Requena Daniela F. , Parra Leonardo A. , Baust Tracy B. , Quiroz Marisol , Leak Rehana K. , Garcia‐Olivares Jennie , Torres Gonzalo E.
Published: April 2009

Synaptic transmission depends on the efficient loading of transmitters into synaptic vesicles by vesicular neurotransmitter transporters. The vesicular monoamine transporter‐2 (VMAT2) is essential for loading monoamines into vesicles and maintaining normal neurotransmission. In an effort to understand the regulatory mechanisms associated with VMAT2, we have embarked upon a systematic search for interacting proteins. Glutathione‐S‐transferase pull‐down assays combined with mass spectrometry led to the identification of the 70‐kDa heat shock cognate protein (Hsc70) as a VMAT2 interacting protein. Co‐immunoprecipitation experiments in brain tissue and heterologous cells confirmed this interaction. A direct binding was observed between the amino terminus and the third cytoplasmic loop of VMAT2, as well as, a region containing the substrate binding and the carboxy‐terminal domains of Hsc70. Furthermore, VMAT2 and Hsc70 co‐fractionated with purified synaptic vesicles obtained from a sucrose gradient, suggesting that this interaction occurs at the synaptic vesicle membrane. The functional significance of this novel VMAT2/Hsc70 interaction was examined by performing vesicular uptake assays in heterologous cells and purified synaptic vesicles from brain tissue. Recombinant Hsc70 produced a dose‐dependent inhibition of VMAT2 activity. This effect was mimicked by the closely related Hsp70 protein. In contrast, VMAT2 activity was not altered in the presence of previously denatured Hsc70 or Hsp70, as well as the unrelated Hsp60 protein; confirming the specificity of the Hsc70 effect. Finally, a purified Hsc70 fragment that binds VMAT2 was sufficient to inhibit VMAT2 activity in synaptic vesicles. Our results suggest an important role for Hsc70 in VMAT2 function and regulation.
p75NTR‐dependent modulation of cellular handling of reactive oxygen species
Authors: Mi Zhiping , Rogers Danny A. , Mirnics Zeljka Korade , Schor Nina Felice
Published: April 2009

Our previous studies demonstrated that p75NTR confers protection against oxidative stress‐induced apoptosis upon PC12 cells; however, the mechanisms responsible for this effect are not known. The present studies reveal decreased mitochondrion membrane potential and increased generation of reactive oxygen species (ROS) in p75NTR‐deficient PC12 cells as well as diminution of ROS generation after transfection of a full‐length p75NTR construct into these cells. They also show that p75NTR deficiency attenuates activation of the phosphatidylinositol 3‐kinase → phospho‐Akt/protein kinase B pathway in PC12 cells by oxidative stress or neurotrophic ligands and inhibition of Akt phosphorylation decreases the glutathione (GSH) content in PC12 cells. In addition, decreased de novo GSH synthesis and increased GSH consumption are observed in p75NTR‐deficient cells. These findings indicate that p75NTR regulates cellular handling of ROS to effect a survival response to oxidative stress.
Plasticity and emerging role of BKCa channels in nociceptive control in neuropathic pain
Authors: Chen Shao‐Rui , Cai You‐Qing , Pan Hui‐Lin
Published: April 2009

Large‐conductance Ca2+‐activated K+ (BKCa, MaxiK) channels are important for the regulation of neuronal excitability. Peripheral nerve injury causes plasticity of primary afferent neurons and spinal dorsal horn neurons, leading to central sensitization and neuropathic pain. However, little is known about changes in the BKCa channels in the dorsal root ganglion (DRG) and spinal dorsal horn and their role in the control of nociception in neuropathic pain. Here we show that L5 and L6 spinal nerve ligation in rats resulted in a substantial reduction in both the mRNA and protein levels of BKCa channels in the DRG but not in the spinal cord. Nerve injury primarily reduced the BKCa channel immunoreactivity in small‐ and medium‐sized DRG neurons. Furthermore, although the BKCa channel immunoreactivity was decreased in the lateral dorsal horn, there was an increase in the BKCa channel immunoreactivity present on dorsal horn neurons near the dorsal root entry zone. Blocking the BKCa channel with iberiotoxin at the spinal level significantly reduced the mechanical nociceptive withdrawal threshold in control and nerve‐injured rats. Intrathecal injection of the BKCa channel opener [1,3‐dihydro‐1‐[2‐hydroxy‐5‐(trifluoromethyl)phenyl]‐5‐(trifluoromethyl)‐2H‐benzimidazol‐2‐one] dose dependently reversed allodynia and hyperalgesia in nerve‐ligated rats but it had no significant effect on nociception in control rats. Our study provides novel information that nerve injury suppresses BKCa channel expression in the DRG and induces a redistribution of BKCa channels in the spinal dorsal horn. BKCa channels are increasingly involved in the control of sensory input in neuropathic pain and may represent a new target for neuropathic pain treatment.
Phosphorylation of the homer‐binding domain of group I metabotropic glutamate receptors by cyclin‐dependent kinase 5
Authors: Orlando Lianna R. , Ayala Ramses , Kett Lauren R. , Curley Allison A. , Duffner Jay , Bragg D. Cristopher , Tsai Li‐Huei , Dunah Anthone W. , Young Anne B.
Published: April 2009

Phosphorylation of neurotransmitter receptors can modify their activity and regulate neuronal excitability. Cyclin‐dependent kinase 5 (cdk5) is a proline‐directed serine/threonine kinase involved not only in neuronal development, but also in synaptic function and plasticity. Here we demonstrate that group I metabotropic glutamate receptors (mGluRs), which modulate post‐synaptic signaling by coupling to intracellular signal transduction pathways, are phosphorylated by cdk5. In vitro kinase assays reveal that cdk5 phosphorylates mGluR5 within the domain of the receptor that interacts with the scaffolding protein homer. Using a novel phosphospecific mGluR antibody, we show that the homer‐binding domain of both mGluR1 and mGluR5 are phosphorylated in vivo, and that inhibition of cdk5 with siRNA decreases the amount of phosphorylated receptor. Furthermore, kinetic binding analysis, by surface plasmon resonance, indicates that phosphorylation of mGluR5 enhances its association with homer. Homer protein complexes in the post‐synaptic density, and their disruption by an activity‐dependent short homer 1a isoform, have been shown to regulate the trafficking and signaling of the mGluRs and impact many neuroadaptive processes. Phosphorylation of the mGluR homer‐binding domain, in contrast to homer 1a induction, provides a novel mechanism for potentially regulating a subset of homer interactions.
REFLECTION ON EUTHANASIA: WESTERN AND AFRICAN NTOMBA PERSPECTIVES ON THE DEATH OF A CHIEF
Authors: BIKOPO DEOGRATIAS BIEMBE , VAN BOGAERT LOUIS‐JACQUES
Published: April 2009

Largely, the concept of energy or vital force, as first analysed by Placide Tempels in Bantu Philosophy, permeates most African ontology systems, worldviews and life views. The Ntomba Chief is chosen because of his above average vital force. This puts him in the position of intermediary between the Supreme Being, the ancestors, and his subordinates. The waning of his energy is incompatible with his position because his energy is that of his tribe. When installed, he takes an oath that, when this happens, he has to accept mohilo, the ‘hastening of death’. In the Chief's case, the hastening of death is not intended to relieve his pain, as it would be with other creatures. The Chief's dying a natural death would result in the loss of the entire community's vital force. Therefore, he has to be killed ritually to avoid that risk. That the Chief agrees to be killed – via a form of advanced directive – poses an ethical dilemma for a Western observer. From the Ntomba perspective, however, where the energy is being, and being is energy, it is the only way to preserve and protect the community's raison d’être.
A qualitative evaluation of an interprofessional learning project
Authors: Jinks Annette M. , Armitage Helen , Pitt Richard
Published: April 2009

The study described in this paper focuses on an interprofessional learning (IPL) in practice project. The project entailed appointing a number of IPL in practice facilitators whose task it was to assist clinical teams to develop opportunities for students to engage in IPL. The evaluation described focuses on one of the initial project sites, a rehabilitation ward in a community hospital. The evaluation aimed to establish a range of differing perspectives on the project including service users, steering group members, the clinical team and participating students. Narrative data were collected using focus groups, one‐to‐one interviews, documentary analysis and postal and electronic questionnaires. Triangulation approaches were used to analyse data and the findings were largely positive. Lessons learnt included such things as practical difficulties of introducing IPL in practice, effective use of lay persons in professional education and the difficulties of engaging medical staff in such initiatives. Limitations of the study include difficulties in getting students to participate in either focus group discussions or one‐to‐one interviews; therefore, alternative data sources had to be deployed, such as e‐mail contact. Conclusions are that even when an experienced IPL facilitator is in post there is a need to foster practice staffs’ commitment to IPL.
Beneficial effects of danshensu, an active component of Salvia miltiorrhiza, on homocysteine metabolism via the trans‐sulphuration pathway in rats
Authors: Cao YG , Chai JG , Chen YC , Zhao J , Zhou J , Shao JP , Ma C , Liu XD , Liu XQ
Published: April 2009

Background and purpose:  Elevated plasma total homocysteine (tHcy) level has been established as an independent risk factor for cardiovascular diseases. Danshensu, an active ingredient of Salvia miltiorrhiza, shows wide cardiovascular benefit. However, in terms of its own methylation, danshensu could elevate tHcy level, which would act against its cardiovascular benefit, thus posing a ‘therapeutic paradox’. As this paradox has not been fully assessed, we have evaluated the effects of danshensu on tHcy levels to uncover the underlying mechanisms.

Experiment approach:  We evaluated the influence of danshensu on homocysteine (Hcy) metabolism in rats with normal tHcy levels and in rat models of elevated tHcy (single intravenous methionine loading model and a hyperhomocysteinemic model after 3 weeks methionine dosing, with and without 3 weeks of danshensu treatment). We also quantified some metabolic intermediates (S‐adenosyl methionine, S‐adenosyl‐l‐homocysteine, cysteine and glutathione) relevant to Hcy metabolism in rat liver and kidney.

Key results:  Acute treatment with a single dose of danshensu in rats with normal tHcy did not change plasma tHcy. In contrast, danshensu significantly lowered tHcy in rats with elevated tHcy. The relatively higher cysteine and glutathione levels after treatment with danshensu indicated that its tHcy‐lowering effect was via increased activity of the trans‐sulphuration pathway.

Conclusions and implications:  Our results suggested that danshensu may act both acutely to increase trans‐sulphuration and after chronic exposure to up‐regulate the activity of the trans‐sulphuration enzymes. The tHcy‐lowering effect of danshensu is another cardiovascular benefit provided by S. miltiorrhiza and suggests a potential tHcy‐lowering therapy.
Role of G12 proteins in oncogenesis and metastasis
Authors: Juneja Juhi , Casey Patrick J
Published: April 2009

The G12 subfamily of heterotrimeric guanine nucleotide‐binding proteins consists of two α subunits, Gα12 and Gα13. These proteins mediate signalling via G protein‐coupled receptors and have been implicated in various physiological and pathophysiological processes. A number of direct and indirect effectors of Gα12 and Gα13 have been identified that mediate, or have been proposed to mediate, the diverse cellular responses accompanying activation of G12 proteins. This review describes the signalling pathways and cellular events stimulated by G12 proteins, with a particular emphasis on processes that are important in regulating cell migration and invasion, and could potentially be involved in the pathophysiology of cancer metastasis. Experimental findings directly implicating G12 proteins in the spread of metastatic disease are also summarized, indicating the importance of targeted inhibition of G12 signalling as a potential therapeutic option for locally advanced and metastatic disease.
Role of α1‐ and β3‐adrenoceptors in the modulation by SR59230A of the effects of MDMA on body temperature in the mouse
Authors: Bexis Sotiria , Docherty James R
Published: April 2009

Background and purpose: We have investigated the ability of the β3‐adrenoceptor antagonist 1‐(2‐ethylphenoxy)‐3‐[[(1S)‐1,2,3,4,‐tetrahydro‐1‐naphthalenyl]amino]‐(2S)‐2‐propanol hydrochloride (SR59230A) to affect the hyperthermia produced by methylenedioxymethamphetamine (MDMA) in conscious mice and whether α1‐adrenoceptor antagonist actions are involved.

Experimental approach: Mice were implanted with temperature probes under anaesthesia, and allowed 2 week recovery. MDMA (20 mg·kg−1) was administered subcutaneously 30 min after vehicle or test antagonist and effects on body temperature monitored by telemetry.

Key results: Following vehicle, MDMA produced a slowly developing hyperthermia, reaching a maximum increase of 1.8°C at 130 min post injection. A low concentration of SR59230A (0.5 mg·kg−1) produced a small but significant attenuation of the slowly developing hyperthermia to MDMA. A high concentration of SR59230A (5 mg·kg−1) revealed a significant and marked early hypothermic reaction to MDMA, an effect that was mimicked by the α1‐adrenoceptor antagonist prazosin. Functional and ligand binding studies revealed actions of SR59230A at α1‐adrenoceptors.

Conclusions and implications: 1‐(2‐ethylphenoxy)‐3‐[[(1S)‐1,2,3,4,‐tetrahydro‐1‐naphthalenyl]amino]‐(2S)‐2‐propanol hydrochloride in high concentrations modulates the hyperthermic actions of MDMA in mice in two ways: by blocking an early α1‐adrenoceptor‐mediated component to reveal a hypothermia, and by a small attenuation of the later hyperthermic component which may possibly be β3‐adrenoceptor‐mediated (this seen with the low concentration of SR59230A). Hence, the major actions of SR59230A in modulating the actions of MDMA on temperature involve α1‐adrenoceptor antagonism.
Identification of an additional supraspinal component to the analgesic mechanism of action of buprenorphine
Authors: Ding Zhe , Raffa Robert B
Published: April 2009

Background and purpose: Buprenorphine displays attributes of opioids, but also some features distinct from them. We examined spinal and supraspinal signal transduction of buprenorphine‐induced anti‐nociception in mice compared with morphine and fentanyl.

Experimental approach: The opioid receptor antagonist naloxone,Pertussistoxin (PTX), Gzprotein antisense and nociceptin/orphanin‐FQ receptor agonist nociceptin, and antagonist, JTC‐801, were injected supraspinally (intracerebroventricular) and spinally (intrathecal). Also the cell‐permeable Ser/Thr protein phosphatase inhibitor okadaic acid was given supraspinally.

Key results: Spinal naloxone (20 µg) or PTX (1 µg) attenuated morphine, fentanyl and buprenorphine (s.c.) anti‐nociception. Supraspinal naloxone or PTX attenuated morphine and fentanyl, but not buprenorphine anti‐nociception. Spinal Gzprotein antisense did not alter buprenorphine, morphine or fentanyl anti‐nociception and supraspinal Gz‐antisense did not alter morphine or fentanyl anti‐nociception. However, supraspinal Gz‐antisense (not random sense) reduced buprenorphine anti‐nociception. Peripheral JTC‐801 (1 mg·kg−1, i.p.) enhanced the ascending (3 mg·kg−1) and descending (30 mg·kg−1) portions of buprenorphine's dose–response curve, but only spinal, not supraspinal, nociceptin (10 nmol·L−1) enhanced buprenorphine anti‐nociception. Intracereboventricular okadaic acid (0.001–10 pg) produced a biphasic low‐dose attenuation, high‐dose enhancement of buprenorphine(3 or 30 mg·kg−1, s.c.) anti‐nociception, but did not affect morphine or fentanyl anti‐nociception.

Conclusions and implications: Buprenorphine has an opioid component to its supraspinal mechanism of analgesic action. Our present results reveal an additional supraspinal component insensitive to naloxone, PTX and nociceptin/orphanin‐FQ, but involving Gzprotein and Ser/Thr protein phosphatase. These data might help explain the unique preclinical and clinical profiles of buprenorphine.
The local anaesthetics proadifen and adiphenine inhibit nicotinic receptors by different molecular mechanisms
Authors: Spitzmaul Guillermo , Gumilar Fernanda , Dilger James P , Bouzat Cecilia
Published: April 2009

Background and purpose: Many local anaesthetics are non‐competitive inhibitors of nicotinic receptors (acetylcholine receptor, AChR). Proadifen induces a high‐affinity state of the receptor, but its mechanism of action and that of an analogue, adiphenine, is unknown.

Experimental approach: We measured the effects of proadifen and adiphenine on single‐channel and macroscopic currents of adult mouse muscle AChR (wild‐type and mutant). We assessed the results in terms of mechanisms and sites of action.

Key results: Both proadifen and adiphenine decreased the frequency of ACh‐induced single‐channel currents. Proadifen did not change cluster properties, but adiphenine decreased cluster duration (36‐fold at 100 µmol·L−1). Preincubation with proadifen decreased the amplitude (IC50= 19 µmol·L−1) without changing the decay rate of macroscopic currents. In contrast, adiphenine did not change amplitude but increased the decay rate (IC50= 15 µmol·L−1). Kinetic measurements demonstrate that proadifen acts on the resting state to induce a desensitized state whose kinetics of recovery resemble those of ACh‐induced desensitization. Adiphenine accelerates desensitization from the open state, but previous application of the drug to resting receptors is required. Both drugs stabilize desensitized states, as evidenced by the decrease in the number of clusters elicited by high ACh concentrations. The inhibition by adiphenine is not affected by proadifen, and the mutation αE262K decreases the sensitivity of the AChR only for adiphenine, indicating that these drugs act at different sites.

Conclusions and implications: Two analogous local anaesthetics bind to different sites and inhibit AChR activity via different mechanisms and conformational states. These results provide new information on drug modulation of AChR.
Pharmacogenetic characterization of indacaterol, a novel β2‐adrenoceptor agonist
Authors: Sayers I , Hawley J , Stewart CE , Billington CK , Henry A , Leighton‐Davies JR , Charlton SJ , Hall IP
Published: April 2009

Background and purpose:

Indacaterol is a novel β2‐adrenoceptor agonist in development for the treatment of chronic obstructive pulmonary disease. The aim of this study was to investigate the comparative pharmacology of indacaterol in recombinant cells expressing the common polymorphic variants of the human β2‐adrenoceptor and in human primary airway smooth muscle (ASM) cells.

Experimental approach:

Chinese hamster ovarian‐K1 cell lines expressing high and low levels of the common human β2‐adrenoceptor variants were generated [Gly16‐Glu27‐Val34‐Thr164(GEVT), RQVT, GQVT] and also the rare GQVI variant. Human primary ASM cells were isolated from explants of trachealis muscle. Adenosine‐3′,5′‐cyclic‐monophosphate production was used as an outcome measure.

Key results:

In both the low‐ and high‐expression recombinant GEVT ‘wild type’ cell lines indacaterol is a high‐efficacy agonist. Salmeterol and formoterol were identified as low‐ and high‐efficacy agonists, respectively, and showed similar potencies to indacaterol irrespective of the β2‐adrenoceptor genotype. The I164 variant cell line was associated with a reduced capacity to generate adenosine‐3′,5′‐cyclic‐monophosphate in response to β2‐adrenoceptor agonist. In the human primary ASM cells indacaterol gave a maximal response intermediate between that of salmeterol and formoterol.

Conclusions and implications:

These data demonstrate that indacaterol is a high‐efficacy agonist in recombinant cell systems but acts with lower efficacy in human primary ASM cells. No marked genotype‐dependent effects were observed for common variants; however, changes in I164 receptor activity were identified, which were dependent on the level of expression of β2‐adrenoceptors.
Pan‐African eclogite facies metamorphism of ultramafic rocks in the Shackleton Range, Antarctica
Authors: ROMER T. , MEZGER K. , SCHMÄDICKE E.
Published: April 2009

In the Shackleton Range of East Antarctica, garnet‐bearing ultramafic rocks occur as lenses in supracrustal high‐grade gneisses. In the presence of olivine, garnet is an unmistakable indicator of eclogite facies metamorphic conditions. The eclogite facies assemblages are only present in ultramafic rocks, particularly in pyroxenites, whereas other lithologies – including metabasites – lack such assemblages. We conclude that under high‐temperature conditions, pyroxenites preserve high‐pressure assemblages better than isofacial metabasites, provided the pressure is high enough to stabilize garnet–olivine assemblages (i.e. ≥18–20 kbar). The Shackleton Range ultramafic rocks experienced a clockwise P–T path and peak conditions of 800–850 °C and 23–25 kbar. These conditions correspond to ∼70 km depth of burial and a metamorphic gradient of 11–12 °C km−1 that is typical of a convergent plate‐margin setting. The age of metamorphism is defined by two garnet–whole‐rock Sm–Nd isochrons that give ages of 525 ± 5 and 520 ± 14 Ma corresponding to the time of the Pan‐African orogeny. These results are evidence of a Pan‐African suture zone within the northern Shackleton Range. This suture marks the site of a palaeo‐subduction zone that likely continues to the Herbert Mountains, where ophiolitic rocks of Neoproterozoic age testify to an ocean basin that was closed during Pan‐African collision. The garnet‐bearing ultramafic rocks in the Shackleton Range are the first known example of eclogite facies metamorphism in Antarctica that is related to the collision of East and West Gondwana and the first example of Pan‐African eclogite facies ultramafic rocks worldwide. Eclogites in the Lanterman Range of the Transantarctic Mountains formed during subduction of the palaeo‐Pacific beneath the East Antarctic craton.
Trunk segmentation of Cambrian eodiscoid trilobites
Authors: Zhang Xi‐guang , Clarkson Euan N. K.
Published: May 2009

SUMMARY
Here we report, from Cambrian Series 2 of Chongqing, southern China, on some three‐dimensionally phosphatized exoskeletons representing a series of instars of a specialized eodiscoid trilobite Badiscus spinosus gen. et sp. nov. The preservation is unusual and its protaspides (the youngest juveniles) belonging to different growth stages markedly exhibit some “embryonic trunk segments,” which imply the specification of all body segments during embryogenesis. This previously unknown style of tagmosis, as being inconsistent with the conventional view of sequential segmentation during postembryonic anamorphosis, emphasizes the complexity of trilobite trunk segmentation during ontogeny and indicates for the first time that epimorphic development, like other known patterns during postembryonic development, may have already been adopted by some of the earliest trilobites.
The concept of the epilepsy syndrome: How useful is it in clinical practice?
Authors: Beghi Ettore
Published: May 2009

An epilepsy syndrome is a disorder characterized by a cluster of symptoms and signs customarily occurring in combination. A syndromic approach to the epilepsies would be of practical value for diagnostic, prognostic, and therapeutic purposes. However, despite considerable efforts by leaders in the field of epileptology and the improved knowledge of the clinical, genetic, imaging, and biologic aspects of epilepsy, there are no measurable objective criteria for recognizing seizure types and epilepsy syndromes as separate diagnostic entities with well‐defined prognostic and therapeutic aspects. The lack of pragmatic, evidence‐based instruments to devise a syndromic classification useful for clinical practice can be explained by the evolving concept of epilepsy syndrome, its dynamic characteristics, the poor prognostic predictivity, and the extremely complex genetic and pathophysiologic mechanisms underlying the epileptic phenomena. In addition, the results of the published reports on epilepsy syndromes are mostly biased by flaws in the study population, design, and statistical analysis. The Classification Core Group of the International League Against Epilepsy (ILAE), which is working on a new classification of the epilepsies, stated that the process of syndrome identification requires that an evidence‐based approach be applied to the published literature and future studies.
Acupuncture for Alcohol Dependence: A Systematic Review
Authors: Cho Seung‐Hun , Whang Wei‐Wan
Published: April 2009

Background:  Acupuncture has been used in the treatment of substance‐related disorders for the past 30 years. However, a systematic review to assess the effect of various types of acupuncture for alcohol dependence has not yet been performed. The present systematic review assessed the results of randomized controlled trials (RCTs).

Methods:  Nineteen electronic databases, including English, Korean, Japanese, and Chinese databases, were systematically searched for RCTs of acupuncture for alcohol dependence up to June 2008 with no language restrictions. The methodological qualities of eligible studies were assessed using the criteria described in the Cochrane Handbook.

Results:  Eleven studies, which comprised a total of 1,110 individual cases, were systematically reviewed. Only 2 of 11 trials reported satisfactorily all quality criteria. Four trials comparing acupuncture treatment and sham treatments reported data for alcohol craving. Three studies reported that there were no significant differences. Among 4 trials comparing acupuncture and no acupuncture with conventional therapies, 3 reported significant reductions. No differences between acupuncture and sham treatments were found for completion rates (Risk Ratio = 1.07, 95% confidence interval, CI = 0.91 to 1.25) or acupuncture and no acupuncture (Risk Ratio = 1.15, 95% CI = 0.79 to 1.67). Only 3 RCTs reported acupuncture‐related adverse events, which were mostly minimal.

Conclusions:  The results of the included studies were equivocal, and the poor methodological quality and the limited number of the trials do not allow any conclusion about the efficacy of acupuncture for treatment of alcohol dependence. More research and well‐designed, rigorous, and large clinical trials are necessary to address these issues.
The Impact of Chronic Cigarette Smoking on Recovery From Cortical Gray Matter Perfusion Deficits in Alcohol Dependence: Longitudinal Arterial Spin Labeling MRI
Authors: Mon Anderson , Durazzo Timothy C. , Gazdzinski Stefan , Meyerhoff Dieter J.
Published: April 2009

Background:  Neuroimaging studies reported cerebral perfusion abnormalities in individuals with alcohol use disorders. However, no longitudinal magnetic resonance imaging (MRI) studies of cerebral perfusion changes during abstinence from alcohol have been reported.

Methods:  Arterial spin labeling MRI was used to evaluate cortical gray matter perfusion changes in short‐term abstinent alcohol dependent individuals in treatment and to assess the impact of chronic cigarette smoking on perfusion changes during abstinence. Seventy‐six patients were scanned at least once. Data from 19 non‐smoking (17 males, 2 females) and 22 smoking (21 males, 1 female) patients scanned at 1 and 5 weeks of abstinence were used to assess perfusion changes over time. Twenty‐eight age‐equated healthy controls (25 males, 3 females) were scanned for cross‐sectional comparison, 13 of them were scanned twice. Given the age range of the cohort (28 to 68 years), age was used as a covariate in the analyses. Mean perfusion was measured in voxels of at least 80% gray matter in the frontal and parietal lobes and related to neurocognitive and substance use measures.

Results:  At 1 week of abstinence, frontal and parietal gray matter perfusion in smoking alcoholics was not significantly different from that in non‐smoking alcoholics, but each group’s perfusion values were significantly lower than in controls. After 5 weeks of abstinence, perfusion of frontal and parietal gray matter in non‐smoking alcoholics was significantly higher than that at baseline. However, in smoking alcoholics, perfusion was not significantly different between the time‐points in either region. The total number of cigarettes smoked per day was negatively correlated with frontal gray matter perfusion measured at 5 weeks of abstinence. Lobar perfusion measures did not correlate significantly with drinking severity or cognitive domain measures at either time‐point.

Conclusion:  Although cerebral perfusion in alcohol dependent individuals shows improvement with abstinence from alcohol, cigarette smoking appears to hinder perfusion improvement.
Immunoglobulin‐E Reactivity to a Glycosylated Food Allergen (Peanuts) Due to Interference With Cross‐Reactive Carbohydrate Determinants in Heavy Drinkers
Authors: Vidal C. , Vizcaino L. , Díaz‐Peromingo J.A. , Garrido M. , Gomez‐Rial J. , Linneberg A. , Gonzalez‐Quintela A.
Published: April 2009

Background:  N‐glycans in plant and invertebrate glycoproteins can induce extensive IgE cross‐reactivity therefore limiting the specificity of in vitro allergy tests. IgE sensitization to N‐glycans (cross‐reactive carbohydrate determinants, CCDs) may be increased in heavy drinkers, who therefore show IgE reactivity to aeroallergens, latex, and Hymenoptera venoms. The peanut, a CCD‐bearing allergen, is the leading cause of severe food allergic reactions in many populations.

Aim of the study:  To investigate the potential interference of CCDs with determinations of IgE to peanuts in heavy drinkers.

Methods:  We determined IgE to peanuts and IgE to a CCD marker (MUXF3, the N‐glycan from bromelain) in 41 heavy drinkers admitted to the hospital and 54 healthy controls. None of the participants reported symptoms of peanut allergy. In cases with positive (≥0.35 kU/l) IgE to peanuts, we performed inhibition assays with a neoglycoprotein consisting of MUXF3 molecules coupled to bovine serum albumin (MUXF3‐BSA) and a similar neoglycoprotein lacking xylose and fucose (MM‐BSA). In the same cases, we screened for IgE to a panel of recombinant nonglycosylated peanut allergens. SDS‐PAGE immunoblotting and inhibition assays were performed in selected cases.

Results:  The prevalence of positive IgE to peanuts was 22 and 3.7% in heavy drinkers and healthy controls, respectively (p < 0.001). Peanut‐IgE positivity was closely related to the presence of IgE to CCDs. In most (8/9) heavy drinkers with positive IgE to peanuts, reactivity was inhibited by preincubation with MUXF3‐BSA, but not with MM‐BSA. IgE binding to multiple bands on immunoblotting studies was also inhibited by MUXF3‐BSA preincubation. IgE to nonglycosylated recombinant peanut allergens was uniformly negative.

Conclusion:  Heavy drinking is associated with clinically asymptomatic IgE reactivity to peanuts, a relevant food allergen, in relation to CCD interference.