bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacological targeting of the KIT growth factor receptor: a therapeutic consideration for mast cell disorders
Authors: Jensen B M , Akin C , Gilfillan A M
Published: May 2008

KIT is a member of the tyrosine kinase family of growth factor receptors which is expressed on a variety of haematopoietic cells including mast cells. Stem cell factor (SCF)‐dependent activation of KIT is critical for mast cell homeostasis and function. However, when KIT is inappropriately activated, accumulation of mast cells in tissues results in mastocytosis. Such dysregulated KIT activation is a manifestation of specific activating point mutations within KIT, with the human D816V mutation considered as a hallmark of human systemic mastocytosis. A number of other activating mutations in KIT have recently been identified and these mutations may also contribute to aberrant mast cell growth. In addition to its role in mast cell growth, differentiation and survival, localized concentration gradients of SCF may control the targeting of mast cells to specific tissues and, once resident within these tissues, mast cell activation by antigen may also be amplified by SCF. Thus, KIT inhibitors may have potential application in multiple conditions linked to mast cells including systemic mastocytosis, anaphylaxis, and asthma. In this review, we discuss the role of KIT in the context of mast cells in these disease states and how recent advances in the development of inhibitors of KIT activity and function may offer novel therapies for the treatment of these disorders.

British Journal of Pharmacology (2008) 154, 1572–1582; doi:10.1038/bjp.2008.204; published online 26 May 2008
Regional haemodynamic responses to adenosine receptor activation vary across time following lipopolysaccharide treatment in conscious rats
Authors: Jolly L , March J E , Kemp P A , Bennett T , Gardiner S M
Published: May 2008

Background and purpose:

Studies using adenosine receptor antagonists have shown that adenosine‐mediated vasodilatations play an important role in the maintenance of regional perfusion during sepsis, but it is unclear whether vascular sensitivity to adenosine is affected. Here, we assessed regional haemodynamic responses to adenosine agonists and antagonists in normal and lipopolysaccharide (LPS)‐treated rats to investigate a possible role for adenosine in the haemodynamic sequelae.

Experimental approach:

Male Sprague–Dawley rats were chronically instrumented with pulsed Doppler flow probes to measure regional haemodynamic responses to adenosine‐receptor agonists (adenosine, 2‐choloro‐N6‐cyclopentyladenosine (CCPA)) and antagonists (8‐phenyltheophylline (8‐PT), 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX)), at selected time points in control and LPS‐treated rats.

Key results:

The responses to 8‐PT were consistent with endogenous adenosine causing bradycardia, and renal and hindquarters vasodilatation in control rats, whereas in LPS‐treated rats, there was evidence for endogenous adenosine causing renal (at 1.5 h) and hindquarters (at 6 h) vasoconstriction. In control animals, exogenous adenosine caused hypotension, tachycardia and widespread vasodilatation, whereas in LPS‐treated rats, the adenosine‐induced renal (at 1.5 h) and hindquarters (at 6 h) vasodilatations were abolished. As enhanced A1receptor‐mediated vasoconstriction could explain the results in LPS‐treated rats, vascular responsiveness to a selective A1‐receptor agonist (CCPA) or antagonist (DPCPX) was assessed. There was no evidence for enhanced vasoconstrictor responsiveness to CCPA in LPS‐treated rats, but DPCPX caused renal vasodilatation, consistent with endogenous adenosine mediating renal vasoconstriction under these conditions.

Conclusions and implications:

The results show changes in adenosine receptor‐mediated cardiovascular effects in endotoxaemia that may have implications for the use of adenosine‐based therapies in sepsis.

British Journal of Pharmacology(2008)154, 1600–1610; doi:10.1038/bjp.2008.205; published online 26 May 2008
The development of a testosterone stimulation test in the Virginia opossum (Didelphis virginiana) and its use in evaluating deslorelin contraception
Authors: Johnston S. D. , Camacho F. C. , Carrillo L. , Guy N. , Govea J. , Martinez O. , Parãs A. , Lisle A. T. , D'Occhio M.
Published: May 2008

The aims of the present study were to examine the variability of testosterone secretion in the Virginia Opossum over a 24 h period and to develop a testosterone stimulation test that would provide an index of the prevailing testosterone biosynthetic capacity of the testes; the latter was used to clinically evaluate the efficacy of a gonadotrophin-releasing hormone agonist contraceptive. Sexually-mature captive opossums (n = 12) located in Africam Safari (Mexico) sampled every 12 h over 24 h consistently showed basal (<0.21 ng mL–1) blood testosterone concentrations. Intra-muscular injection of buserelin (2 μg mL–1) and human chorionic gonadotrophin (hCG; 1000 IU) resulted in an increase (P < 0.05) of plasma testosterone concentrations with maximal concentrations (3.9 ng mL–1 and 5.8 ng mL–1 respectively) occurring 120 min after injection. Plasma testosterone declined relatively rapidly to basal concentrations after 240 min with hCG but remained elevated after the same period of time with buserelin. Male opossums treated with (n = 6) and without (n = 6) a controlled-release deslorelin implant (Suprelorin; 4.7 mg deslorelin) were evaluated over a 10-week period for changes in testosterone secretion (hCG stimulation test) and sperm production (spermatorrhea). At the end of this period, the animals were hemi-castrated and their relative testicular quantitative histology compared. Testosterone concentration decreased over the course of the study in both treated and control animals (P < 0.0001) but there was no apparent effect of deslorelin on testosterone secretion, testicular histology (relative proportions of testicular cell types and seminiferous tubule diameter), or sperm production (presence of sperm in the cauda epididymis or urine)
Ultrastructural evaluation of in vitro-matured canine oocytes
Authors: Viaris de Lesegno Christine , Reynaud Karine , Pechoux Christine , Chebrout Martine , Chastant-Maillard Sylvie
Published: May 2008

Cumulus–oocyte complexes (COCs) were recovered from ovaries of bitches during anoestrus. The ultrastructural organisation of COCs was determined before and after 72 h in vitro maturation (IVM) by transmission electron microscopy. The aim of the study was to determine the quality of oocytes used for IVM and to assess cytoplasmic maturation of IVM metaphase (M) II oocytes. In addition, we examined whether the oocytes that did not reach MII were engaged in an erratic maturation process or whether they were blocked during their progression through a normal maturation process. Before IVM, there were two populations of oocytes: (1) oocytes with a centrally located germinal vesicle, a transcriptionally active aspect and an immature cytoplasm; and (2) oocytes with an eccentric nucleus, a transcriptionally inactive aspect and a more mature cytoplasm. After IVM, most oocytes were still at the germinal vesicle stage with three different patterns and all showing a good synchronisation between nuclear and cytoplasmic maturation. MI oocytes had a similar cytoplasmic maturation to that observed in vivo, but failed to complete meiosis; however, IVM MII oocytes had a very poor cytoplasmic maturation. Ultrastructural analysis demonstrated that even when nuclear maturation is achieved, cytoplasmic maturation may not be obtained in vitro. Thus, all IVM systems should be evaluated on both criteria.
Bovine in vitro oocyte maturation as a model for manipulation of the γ-glutamyl cycle and intraoocyte glutathione
Authors: Curnow E. C. , Ryan J. , Saunders D. , Hayes E. S.
Published: May 2008

Glutathione (GSH) is the main non-enzymatic defence against oxidative stress and is a critical intracellular component required for oocyte maturation. In the present study, several modulators of intracellular GSH were assessed for their effect on the in vitro maturation (IVM) and intracellular GSH content of bovine metaphase (MII) oocytes. Of the five GSH modulators tested, only the cell-permeable GSH donor glutathione ethyl ester (GSH-OEt) significantly increased the GSH content of IVM MII oocytes in a concentration-dependent manner without adversely affecting oocyte maturation rate. The GSH level in IVM MII oocytes was greatly influenced by the presence or absence of cumulus cells and severely restricted when oocytes were cultured in the presence of buthionine sulfoximine (BSO), an inhibitor of GSH synthesis. The addition of GSH-OEt to cumulus-denuded or BSO-treated oocytes increased the GSH content of bovine MII oocytes. Supplementation of the maturation medium with bovine serum albumin (BSA) or fetal calf serum (FCS) affected the GSH content of IVM MII oocytes, with greater levels attained under BSA culture conditions. The addition of GSH-OEt to the maturation medium increased the GSH content of IVM MII oocytes, irrespective of protein source. Spindle morphology, as assessed by immunocytochemistry and confocal microscopy, displayed distinct alterations in response to changes in oocyte GSH levels. GSH depletion caused by BSO treatment tended to widen spindle poles and significantly increased spindle area. Supplementation of the IVM medium with GSH-OEt increased spindle length, but did not significantly alter spindle area or spindle morphology. GSH-OEt represents a novel oocyte-permeable and cumulus cell-independent approach for effective elevation of mammalian oocyte GSH levels.
Inflationary dynamics for matrix eigenvalue problems
Authors: Heller Eric J. , Kaplan Lev , Pollmann Frank
Published: May 2008

Many fields of science and engineering require finding eigenvalues and eigenvectors of large matrices. The solutions can represent oscillatory modes of a bridge, a violin, the disposition of electrons around an atom or molecule, the acoustic modes of a concert hall, or hundreds of other physical quantities. Often only the few eigenpairs with the lowest or highest frequency (extremal solutions) are needed. Methods that have been developed over the past 60 years to solve such problems include the Lanczos algorithm, Jacobi–Davidson techniques, and the conjugate gradient method. Here, we present a way to solve the extremal eigenvalue/eigenvector problem, turning it into a nonlinear classical mechanical system with a modified Lagrangian constraint. The constraint induces exponential inflationary growth of the desired extremal solutions.
Next generation of adeno-associated virus 2 vectors: Point mutations in tyrosines lead to high-efficiency transduction at lower doses
Authors: Zhong Li , Li Baozheng , Mah Cathryn S. , Govindasamy Lakshmanan , Agbandje-McKenna Mavis , Cooper Mario , Herzog Roland W. , Zolotukhin Irene , Warrington Kenneth H. , Weigel-Van Aken Kirsten A. , Hobbs Jacqueline A. , Zolotukhin Sergei , Muzyczka Nicholas , Srivastava Arun
Published: May 2008

Recombinant adeno-associated virus 2 (AAV2) vectors are in use in several Phase I/II clinical trials, but relatively large vector doses are needed to achieve therapeutic benefits. Large vector doses also trigger an immune response as a significant fraction of the vectors fails to traffic efficiently to the nucleus and is targeted for degradation by the host cell proteasome machinery. We have reported that epidermal growth factor receptor protein tyrosine kinase (EGFR-PTK) signaling negatively affects transduction by AAV2 vectors by impairing nuclear transport of the vectors. We have also observed that EGFR-PTK can phosphorylate AAV2 capsids at tyrosine residues. Tyrosine-phosphorylated AAV2 vectors enter cells efficiently but fail to transduce effectively, in part because of ubiquitination of AAV capsids followed by proteasome-mediated degradation. We reasoned that mutations of the surface-exposed tyrosine residues might allow the vectors to evade phosphorylation and subsequent ubiquitination and, thus, prevent proteasome-mediated degradation. Here, we document that site-directed mutagenesis of surface-exposed tyrosine residues leads to production of vectors that transduce HeLa cells ≈10-fold more efficiently
in vitro
and murine hepatocytes nearly 30-fold more efficiently
in vivo
at a log lower vector dose. Therapeutic levels of human Factor IX (F.IX) are also produced at an ≈10-fold reduced vector dose. The increased transduction efficiency of tyrosine-mutant vectors is due to lack of capsid ubiquitination and improved intracellular trafficking to the nucleus. These studies have led to the development of AAV vectors that are capable of high-efficiency transduction at lower doses, which has important implications in their use in human gene therapy.
Understanding ligand-based modulation of the Hsp90 molecular chaperone dynamics at atomic resolution
Authors: Colombo Giorgio , Morra Giulia , Meli Massimiliano , Verkhivker Gennady
Published: May 2008

Molecular switching and ligand-based modulation of the 90-kDa heat-shock protein (Hsp90) chaperone activity may ultimately facilitate conformational coupling to the ATPase cycle along with activation and recruitment of the broad range of client proteins. We present an atomic resolution analysis of the Hsp90 N-terminal domain (NTD) binding energy landscape by simulating protein dynamics with a range of binding partners. We show that the activity of the molecular chaperone may be linked to (
i
) local folding-unfolding transitions and conformational switching of the “active site lid” upon binding and (
ii
) differences in the underlying protein dynamics as a function of the binding partner. This study suggests that structural plasticity of the Hsp90 NTD can be exploited by the molecular chaperone machinery to modulate enhanced structural rigidity during ATP binding and increased protein flexibility as a consequence of the inhibitor binding. The present study agrees with the experimental structural data and provides a plausible molecular model for understanding mechanisms of modulation of molecular chaperone activities by binding partners.
Iconicity in different types of gestures
Authors: Poggi Isabella
Published: May 2008

The paper presents a framework for classifying gestures in terms of different parameters, and shows that the parameter of iconicity cuts across that of cognitive construction, which distinguishes codified gestures — those represented in memory as stable signal–meaning pairs — from creative ones — those invented on the spot on the basis of a few generative rules. While creative gestures are necessarily iconic, because they can be understood only thanks to their iconicity, codified gestures can be iconic too. A model for the generation of iconic gestures is presented, according to which, to create a new gesture, people select the features of the meaning to imitate in terms of their distinctiveness, ease of representation and ontological type. Finally, some principles for measuring the iconicity of gestures of Hearers and Signs of the Deaf are illustrated, thus outlining the continuity of iconic devices between creative and codified gestures.
Metaphors in sign languages and in co-verbal gesturing
Authors: Russo Cardona Tommaso
Published: May 2008

In analyses of the grammatical structure of sign languages (Liddell, 2003), “classifier forms” which play a major role in these spatialised grammars, are looked upon as a “gestural” component of sign language. Kendon (2004) pointed out that some of the organizational principles of co-verbal gesturing can be compared to “classifiers” in sign languages. In this paper drawing on previous analyses of LIS (Italian Sign Language) metaphors in discourse (Russo, 2004a, 2005) the role of “classifier forms” in SL metaphors is examined and compared with some aspects of gestural metaphors produced during academic lectures in Italian. It is shown that similarities and differences between the two communicative devices can be pointed out only if the multimodal organization of both face-to-face speech activity and face-to-face sign language communication is taken into account. The gestural actions produced by speakers and the non-manual gestures produced by signers are interpreted as framing a speech act unit in this way providing a perspective for the interpretation of the lexical items within it. The distinction between langue and parole proposed by Ferdinand de Saussure (1916) is discussed and reframed by this analysis.
MEC-2 and MEC-6 in the Caenorhabditis elegans Sensory Mechanotransduction Complex: Auxiliary Subunits that Enable Channel Activity
Authors: Brown Austin L. , Liao Zhiwen , Goodman Miriam B.
Published: May 2008

The ion channel formed by the homologous proteins MEC-4 and MEC-10 forms the core of a sensory mechanotransduction channel in Caenorhabditis elegans. Although the products of other mec genes are key players in the biophysics of transduction, the mechanism by which they contribute to the properties of the channel is unknown. Here, we investigate the role of two auxiliary channel subunits, MEC-2 (stomatin-like) and MEC-6 (paraoxonase-like), by coexpressing them with constitutively active MEC-4/MEC-10 heteromeric channels in Xenopus oocytes. This work extends prior work demonstrating that MEC-2 and MEC-6 synergistically increase macroscopic current. We use single-channel recordings and biochemistry to show that these auxiliary subunits alter function by increasing the number of channels in an active state rather than by dramatically affecting either single-channel properties or surface expression. We also use two-electrode voltage clamp and outside-out macropatch recording to examine the effects of divalent cations and proteases, known regulators of channel family members. Finally, we examine the role of cholesterol binding in the mechanism of MEC-2 action by measuring whole-cell and single-channel currents in MEC-2 mutants deficient in cholesterol binding. We suggest that MEC-2 and MEC-6 play essential roles in modulating both the local membrane environment of MEC-4/MEC-10 channels and the availability of such channels to be gated by force in vivo.
Atomic Constraints between the Voltage Sensor and the Pore Domain in a Voltage-gated K+ Channel of Known Structure
Authors: Lewis Anthony , Jogini Vishwanath , Blachowicz Lydia , Lainé Muriel , Roux Benoît
Published: May 2008

In voltage-gated K+ channels (Kv), membrane depolarization promotes a structural reorganization of each of the four voltage sensor domains surrounding the conducting pore, inducing its opening. Although the crystal structure of Kv1.2 provided the first atomic resolution view of a eukaryotic Kv channel, several components of the voltage sensors remain poorly resolved. In particular, the position and orientation of the charged arginine side chains in the S4 transmembrane segments remain controversial. Here we investigate the proximity of S4 and the pore domain in functional Kv1.2 channels in a native membrane environment using electrophysiological analysis of intersubunit histidine metallic bridges formed between the first arginine of S4 (R294) and residues A351 or D352 of the pore domain. We show that histidine pairs are able to bind Zn2+ or Cd2+ with high affinity, demonstrating their close physical proximity. The results of molecular dynamics simulations, consistent with electrophysiological data, indicate that the position of the S4 helix in the functional open-activated state could be shifted by ∼7–8 Å and rotated counterclockwise by 37° along its main axis relative to its position observed in the Kv1.2 x-ray structure. A structural model is provided for this conformation. The results further highlight the dynamic and flexible nature of the voltage sensor.
KCNQ1 and KCNE1 in the IKs Channel Complex Make State-dependent Contacts in their Extracellular Domains
Authors: Xu Xulin , Jiang Min , Hsu Kai-Ling , Zhang Mei , Tseng Gea-Ny
Published: May 2008

KCNQ1 and KCNE1 (Q1 and E1) associate to form the slow delayed rectifier IKs channels in the heart. A short stretch of eight amino acids at the extracellular end of S1 in Q1 (positions 140–147) harbors six arrhythmia-associated mutations. Some of these mutations affect the Q1 channel function only when coexpressed with E1, suggesting that this Q1 region may engage in the interaction with E1 critical for the IKs channel function. Identifying the Q1/E1 contact points here may provide new insights into how the IKs channel operates. We focus on Q1 position 145 and E1 positions 40–43. Replacing all native cysteine (Cys) in Q1 and introducing Cys into the above Q1 and E1 positions do not significantly perturb the Q1 channel function or Q1/E1 interactions. Immunoblot experiments on COS-7 cells reveal that Q1 145C can form disulfide bonds with E1 40C and 41C, but not E1 42C or 43C. Correspondingly, voltage clamp experiments in oocytes reveal that Q1 145C coexpressed with E1 40C or E1 41C manifests unique gating behavior and DTT sensitivity. Our data suggest that E1 40C and 41C come close to Q1 145C in the activated and resting states, respectively, to allow disulfide bond formation. These data and those in the literature lead us to propose a structural model for the Q1/E1 channel complex, in which E1 is located between S1, S4, and S6 of three separate Q1 subunits. We propose that E1 is not a passive partner of the Q1 channel, but instead can engage in molecular motions during IKs gating.
Development of a Guideline for the Management of Ventilator-Associated Pneumonia Based on Local Microbiologic Findings and Impact of the Guideline on Antimicrobial Use Practices
Authors: Dellit Timothy H. , Chan Jeannie D. , Skerrett Shawn J. , Nathens Avery B.
Published: May 2008

Objective.

To describe the development of a guideline for the management of ventilator-associated pneumonia (VAP) based on local microbiologic findings and to evaluate the impact of the guideline on antimicrobial use practices.

Design.

Retrospective comparison of antimicrobial use practices before and after implementation of the guideline.

Setting.

Intensive care units at Harborview Medical Center, Seattle, Washington, a university-affiliated urban teaching hospital.

Patients.

A total of 819 patients who received mechanical ventilation and who underwent quantitative bronchoscopy between July 1, 2003, and June 30, 2005, for suspected VAP.

Interventions.

Implementation of an evidence-based VAP guideline that focused on the use of quantitative bronchoscopy for diagnosis, administration of empirical antimicrobial therapy based on local microbiologic findings and resistance patterns, tailoring definitive antimicrobial therapy on the basis of culture results, and appropriate duration of therapy.

Results.

During the baseline period, 168 (46.7%) of 360 patients had quantitative cultures that met the diagnostic criteria for VAP, compared with 216 (47.1%) of 459 patients in the period after the guideline was implemented. The pathogens responsible for VAP remained similar between the 2 periods, except that the prevalence of VAP due to carbapenem-resistant Acinetobacter species increased from 1.8% to 15.3% (P < .001), particularly in late-onset VAP. Compared with the baseline period, there was an improvement in antimicrobial use practices after implementation of the guideline: antimicrobial therapy was more frequently tailored on the basis of quantitative culture results (103 [61.3%] of 168 vs 150 [69.4%] of 216 patients; P = .034), there was an increase in the use of appropriate definitive therapy (135 [80.4%] of 168 vs 193 [89.4%] of 216 patients; P = .001), and there wasadecrease in the mean duration oftherapy (12.0vs 10.7days; P = .0014). The all-cause mortality rate was similar in the periods before and after the guideline was implemented (38 [22.6%] of 168 vs 46 [21.3%] of 216 patients; P = .756).

Conclusions.

Implementation of a guideline for the management of VAP that incorporated the use of quantitative bronchoscopy, the use of empirical therapy based on local microbiologic findings, tailoring of therapy on the basis of culture results, and use of shortened durations of therapy led to significant improvements in antimicrobial use practices without adversely affecting the all-cause mortality rate.
Nestlé in the Ottoman Empire: Global Marketing with Local Flavor 1870–1927
Authors: Koese Yavuz
Published: May 2008

This paper examines the marketing activities of Nestlé in the Ottoman Empire between 1870 and 1927. Nestlé began with the same strategy it had developed in Western markets for the Ottoman market. But the Ottoman political, social, and cultural context differed considerably from Europe. The article explores how Nestl´e responded to this complex marketing environment with increasing local differentiation. It goes on to demonstrate that as well as its variegated approaches to the ethnically, religiously, and culturally heterogeneous urban consumer, Nestlé's success derived from its ability to connect with different strata of society. I argue that the Ottoman Empire, and especially its capital Istanbul, were strategically essential to Nestl´e's development of its adaptive global marketing strategy.
Hypogonadism is Common in Men With Myopathies
Authors: Al-Harbi Talal M , Bainbridge Laura J , McQueen Matthew J , Tarnopolsky Mark A
Published: May 2008

Background:

Hypogonadism has been described in patients with myotonic muscular dystrophy type 1 but has not been evaluated in other myopathies.

Methods:

We measured total and free serum testosterone levels in 59 men with myotonic muscular dystrophy type 1 (N = 12), facioscapulohumeral muscular dystrophy (N = 11), dystrophinopathy (N = 12), metabolic myopathy (N = 7), and inclusion body myositis (N = 17) and compared these with the normal reference interval.

Results:

Thirty-two of the 59 (54%) participants had low total testosterone, 23 (39%) had low total and free values, and 5 (8%) had low free with normal total levels. There were no significant differences in the prevalence of hypogonadism between those with myotonic muscular dystrophy type 1 and the other groups even after considering age as a confounder.

Conclusions:

Hypogonadism is common in men with myopathies, and with the importance of testosterone in the maintenance of muscle mass, treatment of hypogonadism should be considered.
The structure of an archaeal homodimeric ligase which has RNA circularization activity
Authors: Brooks Mark Adrian , Meslet‐Cladiére Laurence , Graille Marc , Kuhn Joëlle , Blondeau Karine , Myllykallio Hannu , van Tilbeurgh Herman
Published: May 2008

The genome of Pyrococcus abyssi contains two open reading frames encoding proteins which had been previously predicted to be DNA ligases, Pab2002 and Pab1020. We show that while the former is indeed a DNA ligase, Pab1020 had no effect on the substrate deoxyoligo‐ribonucleotides tested. Instead, Pab1020 catalyzes the nucleotidylation of oligo‐ribonucleotides in an ATP‐dependent reaction, suggesting that it is an RNA ligase. We have solved the structure of Pab1020 in complex with the ATP analog AMPPNP by single‐wavelength anomalous dispersion (SAD), elucidating a structure with high structural similarity to the catalytic domains of two RNA ligases from the bacteriophage T4. Additional carboxy‐terminal domains are also present, and one of these mediates contacts with a second protomer, which is related by noncrystallographic symmetry, generating a homodimeric structure. These C‐terminal domains are terminated by short domain swaps which themselves end within 5 Å of the active sites of the partner molecules. Additionally, we show that the protein is indeed capable of circularizing RNA molecules in an ATP‐dependent reaction. These structural and biochemical results provide an insight into the potential physiological roles of Pab1020.
Stable isotopes identify the natal origins of a generalist brood parasite, the brown‐headed cowbird Molothrus ater
Authors: Kosciuch Karl L. , Rivers James W. , Sandercock Brett K.
Published: May 2008

Identifying the natal origins of brood parasites is a major challenge that usually requires labor‐intensive searching for nests of host species. Stable isotope analysis of feathers and other body tissues of parasitic young could be a possible tool for determining natal origins if tissues reflect the isotopic composition of the diet fed to nestlings. We measured the carbon (13C) and nitrogen (15N) isotope compositions of feathers for two age‐classes of brown‐headed cowbirds Molothrus ater at the Konza Prairie Biological Station near Manhattan, Kansas: nestlings raised by five species of songbird hosts in two different habitats, and juveniles captured after independence. Isotope values from cowbird nestlings did not differ among host species and we were unable to assign juvenile cowbirds to their natal hosts. However, nestlings raised in grassland habitat had feathers that contained significantly higher δ13C values and lower δ15N values than nestlings raised in shrub habitats. In addition, independent juveniles had isotopic signatures that were similar to cowbird nestlings raised on shrub habitats. Although dickcissel Spiza americana comprised the majority of samples from shrub habitats, our conclusions reflect the natural pattern of parasitism at the site and should be representative of cowbirds raised at Konza. We conclude that stable isotope analysis of feathers is effective for determining the natal origins of parasitic young if isotope values from nestlings are isotopically distinct among habitats.
Male‐biased parasitism by common helminths is not explained by sex differences in body size or spleen mass of breeding cormorants Phalacrocorax auritus
Authors: Robinson Stacey A. , Forbes Mark R. , Hebert Craig E. , Daniel McLaughlin J.
Published: May 2008

In vertebrates, males are often more parasitised than conspecific females. This bias in parasitism might result from sex differences in parasite exposure and/or susceptibility to infection. Such information is important for testing hypotheses about allocation of resources to life histories of males and females and for testing hypotheses about factors thought to influence parasite fitness and parasite dynamics. We tested whether double‐crested cormorants Phalacrocorax auritus exhibit male‐biased parasitism by gut helminths. The prevalence of nematode Contracaecum spp. and trematode Drepanocaphalus spathans infections was ∼90% and 39%, respectively. Cestode, primarily Paradilepis caballeroi and acanthocephalan Andracantha gravida infections were less common (<10%). Male and female cormorants did not differ in prevalence of infection by any helminth species. However, males had twice the abundance and intensity of Contracaecum spp. infections and twice the intensity of D. spathans infections than found in females. For common parasites showing male‐biased parasitism, degree of parasitism was also unrelated to body size or mass in either sex. Males and females did not differ in spleen mass and spleen mass was unrelated to abundance of common parasites. Furthermore, abundance of trematodes and nematodes was not correlated. At present, male biases in parasitism by nematodes and trematodes in cormorants are independent patterns that remain unexplained, but are most likely attributable to sex differences in exposure and/or immunological differences not yet assessed.
Wheat leaf rust caused by Puccinia triticina
Authors: BOLTON MELVIN D. , KOLMER JAMES A. , GARVIN DAVID F.
Published: May 2008

Leaf rust, caused by Puccinia triticina, is the most common rust disease of wheat. The fungus is an obligate parasite capable of producing infectious urediniospores as long as infected leaf tissue remains alive. Urediniospores can be wind‐disseminated and infect host plants hundreds of kilometres from their source plant, which can result in wheat leaf rust epidemics on a continental scale. This review summarizes current knowledge of the P. triticina/wheat interaction with emphasis on the infection process, molecular aspects of pathogenicity, rust resistance genes in wheat, genetics of the host parasite interaction, and the population biology of P. triticina.

Taxonomy:   Puccinia triticina Eriks.: kingdom Fungi, phylum Basidiomycota, class Urediniomycetes, order Uredinales, family Pucciniaceae, genus Puccinia.

Host range:   Telial/uredinial (primary) hosts: common wheat (Triticum aestivum L.), durum wheat (T. turgidum L. var. durum), cultivated emmer wheat (T. dicoccon) and wild emmer wheat (T. dicoccoides), Aegilops speltoides, goatgrass (Ae. cylindrica), and triticale (X Triticosecale). Pycnial/aecial (alternative) hosts: Thalictrum speciosissimum (= T. flavum glaucum) and Isopyrum fumaroides.

Identification:   Leaf rust is characterized by the uredinial stage. Uredinia are up to 1.5 mm in diameter, erumpent, round to ovoid, with orange to brown uredinia that are scattered on both the upper and the lower leaf surfaces of the primary host. Uredinia produce urediniospores that are sub‐globoid, average 20 µm in diameter and are orange–brown, with up to eight germ pores scattered in thick, echinulate walls.

Disease symptoms:   Wheat varieties that are fully susceptible have large uredinia without causing chlorosis or necrosis in the host tissues. Resistant wheat varieties are characterized by various responses from small hypersensitive flecks to small to moderate size uredinia that may be surrounded by chlorotic and/or necrotic zones.

Useful website:   USDA Cereal Disease Laboratory: http://www.ars.usda.gov/mwa/cdl
Learning how we learn: an ethnographic study in a neonatal intensive care unit
Authors: Hunter Cynthia Louise , Spence Kaye , McKenna Kate , Iedema Rick
Published: May 2008

Title.  Learning how we learn: an ethnographic study in a neonatal intensive care unit.

Aim.  This paper is a report of a study to identify how nurse clinicians learn with and from each other in the workplace.

Background.  Clinicians’ everyday practices and interactions with each other have recently been targeted as areas of research, because it is there that quality of care and patient safety are achieved. Orientation of new nurses and doctors into a specialty unit often results in stress.

Method.  An ethnographic approach was used, including a 12‐month period of fieldwork observations involving participation and in‐depth interviews with nurse, doctor and allied health clinicians in their workplace. The data were collected in 2005–2006 in a paediatric teaching hospital in Australia.

Findings.  The findings were grouped into four dimensions: orientation of nurses, orientation of medical registrars, preceptoring and decision‐making. The orientation of new staff (nursing and medical) is a complex and multi‐layered process which accommodates multiple kinds of learning, in addition to formal learning. Workplace learning also can be informal, incidental, interpersonal and interactive. Interactive and interpersonal learning and the transfer of knowledge include codified and tacit knowledge as well as intuitive understandings of ‘how we do things here’.

Conclusion.  Research into how nurses learn is crucial for illuminating learning that is non‐formal and less recognized than more formal kinds. To provide a safe practice environment built on a foundation of knowledge and best practice, there needs to be an allocation of time in the busy workday for learning and reflection.
‘Do no harm’? Professional regulation of disabled nursing students and nurses in Great Britain
Authors: Sin Chih Hoong , Fong Janice
Published: May 2008

Title.  ‘Do no harm’? Professional regulation of disabled nursing students and nurses in Great Britain.

Aim. This paper is a report of the findings of a General Formal Investigation launched by the Disability Rights Commission, Great Britain into the impact of regulatory fitness standards on disabled people, and on nursing students and nurses in particular.

Background. The potential for systemic discrimination against disabled nursing professionals lies in the existence and nature of regulatory fitness standards, as well as in how these are interpreted and implemented in practice.

Methods. A review of relevant legislation, regulation and guidance was conducted to explore the interaction of the regulatory framework with the Disability Discrimination Act. A formal call to key national stakeholder organizations solicited information on perceptions of the regulatory framework and the adequacy of guidance issued. Independent research was commissioned on disabled people’s disclosure of disability, informal and formal decision‐making around fitness within the educational, and employment contexts. An Inquiry Panel examined all evidence sources, solicited further oral evidence from key organizations, and developed recommendations.

Findings. No mention was found of the Disability Discrimination Act in any regulation and guidance governing nursing prior to 2006. There are particular requirements for ‘good health and good character’. Respondents from key national stakeholder organizations, higher educational institutions and employers struggle to interpret the fitness requirements consistently. Implementation is variable, with reliance on ad hoc self‐initiated strategies. The variability of interpretation and implementation can lead to discrimination against disabled people.

Conclusion. The imprecision of fitness requirements and variability of implementation raise serious doubts about their utility in managing risk.
Striving for independence: experiences and needs of service users with life limiting conditions
Authors: Cotterell Phil
Published: May 2008

Title.  Striving for independence: experiences and needs of service users with lifelimiting conditions.

Aim.  This paper is a report of a study to explore what service users with a range of life‐limiting conditions identify as their key experiences and needs generally and, specifically, from health and social care services.

Background.  Whilst internationally palliative care has a primary focus on service users who have cancer, there is growing evidence that those with non‐cancer life‐limiting conditions have similar palliative care needs. The literature has mainly been focused on independence, choice and control at an individual level, with wider influences on the maintenance or attainment of independence ignored.

Method.  A participatory approach was used in 2003–2004, with both the researcher and a group of service users working together in all stages of the study. Twenty‐five participants in receipt of support from an acute hospital, primary care, social services and a hospice took part. Face‐to‐face individual interviews and small discussion groups were conducted and data were analysed thematically.

Findings.  Eight different but interconnected themes were identified. Independence/dependence was an overarching theme, with negotiation between independence and dependence being evident across all themes. This theme and the influence of health and social care services on the experience of living with life‐limiting conditions are the focus of this paper.

Conclusion.  Palliative care and practitioners should focus on maximizing independence at both the individual and structural levels. How services for those with life‐limiting conditions are provided and relationships with health and social care staff can directly impact on an individual’s experience of independence, choice and control.
Stigma in the context of hepatitis C: concept analysis
Authors: Butt Gail
Published: May 2008

Title. Stigma in the context of hepatitis C: concept analysis.

Aim. This paper is a report of a concept analysis of stigma in the context of hepatitis C.

Background. Stigma is a complex and powerful social phenomenon that influences the course of illness and marginalizes populations. Knowledge of hepatitis C stigma is central to assisting people with hepatitis C self‐manage their illness and reduce the disease burden.

Data sources. Thirty studies from 1995 to 2007 located in health and social sciences databases constituted the data for an evolutionary concept analysis and ecological theory guide the review.

Findings. Stigma is a subjective and variable, perceived and/or experienced phenomenon, most frequently but not exclusively viewed as negative, that has interrelated intrapersonal, interpersonal and structural or institutional dimensions. The antecedents of hepatitis C stigma are help‐seeking situations most frequently occurring in healthcare settings. Attributes include the association of hepatitis C with illicit drug use, fear of transmission of a contagious and life‐threatening infection, acceptable level of risk, and the power to impose restrictions on the part of healthcare practitioners, family and friendship networks and society. Stigma consequences are mainly, but not exclusively, negative.

Conclusion. A central and distinctive feature of hepatitis C stigma in the Western world is its association with illicit drug use. Further research is required to understand the complexities associated with the sociocultural, situational and structural features that influence the stigma experience as well as the trajectory of the disease to understand the concept better and inform nursing practice.
Effectiveness of relaxation for postoperative pain and anxiety: randomized controlled trial
Authors: Seers Kate , Crichton Nicola , Tutton Liz , Smith Lisa , Saunders Teresa
Published: May 2008

Title.  Effectiveness of relaxation for postoperative pain and anxiety: randomizedcontrolled trial

Aim.  This paper is a report of a study to determine the effectiveness of jaw and total body relaxation for postoperative pain, anxiety and level of relaxation, and to determine any patient expectancy effects.

Background.  Relaxation is increasingly suggested as a pain control technique that can be used by nurses in daily practice. A systematic review of the effectiveness of relaxation for postoperative pain relief revealed many poorly designed studies and only some weak evidence supporting the use of relaxation for postoperative pain.

Method.  A randomized controlled trial (n = 118) was conducted between 2002 and 2003 to compare total body relaxation, jaw relaxation, attention control and usual care. Consenting patients admitted for elective orthopaedic surgery aged 18 or over, able to speak English and able to tense and relax more than two muscle groups were included. Pain at rest and on movement, anxiety and relaxation were assessed at pre‐admission clinic, pre‐intervention, immediately post‐intervention and 1, 2, 3 and 4 hours later. However, the trial was under‐powered.

Findings.  There were statistically significant reductions in pain at rest from pre‐ to post‐intervention for both the relaxation groups and the attention control group. The usual care group had a small increase in pain, whilst the other three groups had similar small decreases in pain. There was no statistically significant difference in anxiety or relaxation scores pre‐ to post‐intervention between groups.

Conclusion.  Jaw relaxation could give these orthopaedic patients a small, very short‐lasting additional amount of pain relief, and it may be that staff and patients feel this small benefit to be worthwhile.
Parent participation in the care of hospitalized children: a systematic review
Authors: Power Nina , Franck Linda
Published: May 2008

Title.  Parent participation in the care of hospitalized children: a systematic review

Aim.  This paper is a report of a systematic literature review of research on parent participation in the care of hospitalized children.

Background.  Research prior to 1994 found that parents want to participate in basic child care activities normally performed at home. Nurses expected parents to participate in these activities but were reluctant for parents to take on technical roles. Further research has been conducted over the last decade, but has not been systematically reviewed.

Data sources.  A search of biomedical research, published between January 1994 and June 2006, was conducted using the databases CINAHL, PsychInfo, Embase and Medline. The search terms related to parents, participation and hospitalized children.

Methods.  A systematic review was conducted and study findings were extracted, summarized and critiqued in relation to their contribution to knowledge about parent participation.

Results.  Twenty‐one descriptive studies were found which investigated the following dimensions of parent participation: parents’ and healthcare professionals’ needs, desires and expectations; parent and healthcare professionals’ attitudes; parent roles and healthcare professional facilitation activities. Ways in which nurses gave parents instruction and guidance to participate effectively in the care of their hospitalized child were examined in five intervention studies.

Conclusion.  Recent research has confirmed parents’ desire and expectations to participate in their child’s care and shown how the nature of their participation has evolved. The attitudes and activities of healthcare professionals are both barriers and facilitators to parent participation. Further research is needed to examine how parents’ expectations differ between specialties and acute and chronic care and ways of facilitating parent participation.
Disaster preparedness among Hong Kong nurses
Authors: Fung Olivia W.M. , Loke Alice Yuen , Lai Claudia K.Y.
Published: May 2008

Title.  Disaster preparedness among Hong Kong nurses

Aim.  This paper is a report of a survey to explore Hong Kong nurses’ disaster preparedness.

Background.  Increasingly frequent global disasters are posing threats to human health and life. The World Health Organization has called for countries to have detailed plans at all levels in order to be prepared for disasters that may arise.

Method.  A questionnaire was distributed to convenience samples of practising Registered Nurses studying in Master’s degree programmes at a Hong Kong university in 2007.

Results.  Of a possible 174, 164 questionnaires were returned (Response rate 94%). Almost all nurses (97·6%) considered the government health department to be the organization most involved in disastrous situations. The majority (84·8%) were aware of the existence of a protocol on disaster management at their workplace. About one‐third would respond in accordance with protocol (38·4%) or rely on directions from their immediate supervisors (34·8%) if a disaster occurred. Almost all the nurses (97%) considered themselves not adequately prepared for disasters. They recognized that a protocol for disaster management (85·4%) and training and drills for disasters (both 84·1%) are useful tools.

Conclusion.  Nurses in Hong Kong are not adequately prepared for disasters, but are aware of the need for such preparation. Disaster management training should be included in the basic education of nurses.