bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promoting evidence‐based care through a clinical research fellowship programme
Authors: Milne Donna J , Krishnasamy Meinir , Johnston Linda , Aranda Sanchia 
Published: August 2007

Aim.  This paper reports on the development and evaluation of a multidisciplinary critical appraisal and research utilization‐training programme at one organization with the aim of demonstrating a potential approach to the challenge of ensuring practice is evidence based.Background.  Considerable time and attention is devoted to developing and evaluating new clinical innovations. Nevertheless, it is estimated that a quarter of patients continue to receive treatments that are unnecessary or potentially harmful.Design.  A cross‐sectional qualitative evaluation survey of nurses and allied health staff participating in the training programme.Methods.  After running the programme twice at this organization we sought to evaluate the impact of the programme. Participants were asked to write answers to open‐ended questions to examine personal and professional outcomes of participation.Results.  All respondents found the programme to be worthwhile and beneficial to their everyday practice. Importantly, participants reported feeling more confident when discussing clinical issues within the multidisciplinary team. The majority have presented their work via oral presentations or in publications and many have gone on to enrol in higher degrees.Conclusions.  A critical appraisal and research utilization programme, as described here, has benefits for clinicians in terms of building confidence, knowledge and skill acquisition and also for the organization in terms of provision of evidence‐based care and quality and safety. It successfully addresses commonly reported barriers to research utilization.Relevance to clinical practice.  A programme such as the Clinical Research Fellowship increases clinicians’ ability and confidence to generate research questions that are meaningful to practice and then investigate the issue in a rigorous and timely manner.
Alternative trans‐splicing of the Trypanosoma cruzi LYT1 gene transcript results in compartmental and functional switch for the encoded protein
Authors: Benabdellah Karim , González‐Rey Elena , González Antonio 
Published: August 2007

Summary Trypanosma cruzi has a complex life cycle that includes infective and non‐infective stages in distinct hosts. Control of gene expression by the parasite must adjust to rather diverse circumstances. Through stage‐regulated, alternative trans‐splicing of the primary transcript, the T. cruzi LYT1 gene generates two protein products differing in the presence or absence of 28 amino acids at their amino end. We find that the shorter protein, kLYT1, is located at two spots in the mitochondrial kinetoflagellar zone and its expression reverts the ‘accelerated stage development’ phenotype of the LYT1‐null mutant. The larger product, mLYT1, localizes on the plasma membrane. The signal for membrane localization presents characteristics of a type II anchor including the possibility of cleavage. Expression of mLYT1 reverts the ‘loss of virulence’ phenotype associated to diminished haemolytic activity at acid pH, but stage development still progresses at an accelerated rate. This compartmentalization switch of LYT1 results in two surprisingly different functions: haemolytic activity at acid pH for mLYT1, and a putative involvement in mitochondrial metabolism for kLYT1. We conclude that alternative trans‐splicing plays an important role in stage‐regulated control of gene expression in trypanosomatids.
BIOMARKER: Assessment of alcohol consumption among hepatitis C‐positive people receiving opioid maintenance treatment using direct ethanol metabolites and self‐report: a pilot study
Authors: Wurst Friedrich M. , Haber Paul S. , Wiesbeck Gerhard , Watson Bianca , Wallace Cate , Whitfield John B. , Halter Claudia , Weinmann Wolfgang , Conigrave Katherine M. 
Published: August 2007

ABSTRACTThis study was conducted to identify the alcohol consumption among hepatitis C‐positive people receiving opioid maintenance therapy using self‐report and biomarkers. A total of 49 people (28 male, 21 female) were hepatitis C virus (HCV) positive and were included. The alcohol use disorder identification test (AUDIT) and self‐reported ethanol intake in the last 28 days were assessed. In addition to gamma‐glutamyl‐transferase (GGT) and mean corpuscular volume (MCV), ethyl glucuronide (EtG) and ethyl sulphate (EtS) were determined in serum and urine (UEtG, UEtS, SEtG) using liquid chromatography/tandem mass‐spectroscopy (LC/MS‐MS) with deuterated internal standards. Abstinence from alcohol was reported for the last 28 days by 13 participants and for the last 7 days by 22. AUDIT was > 8 in 27 cases. The maximum values were 34.8 mg/l for UEtG, 5.3 mg/l for UEtS and 0.15 for SEtG. Among the 19 UEtG positives, 8 had not reported any ethanol intake in the 7 days prior to the study. Six participants reported intake of up to 320 g of ethanol in the last 7 days, but were negative for SEtG, UEtG and UEtS. Self‐reported ethanol intake in the last 28 days correlated with AUDIT score (r = 0.733, P < 0.001), with the direct ethanol metabolites and MCV. In this population, abstinence and episodic heavy drinking are more common than in the general population. Episodic heavy drinking is a significant cause of acute risk in this population. Results from biomarker testing could indicate cases of under‐ as well as over‐reporting of alcohol consumption. Further research on the diagnostic accuracy of direct ethanol metabolites, including the use of phosphatidylethanol (PEth), in this setting is needed.
Inhibition of the membrane attack complex of complement for induction of accommodation in the hamster‐to‐rat heart transplant model
Authors: Suhr Benjamin D. , Black Sylvester M. , Guzman‐Paz Manuel , Matas Arthur J. , Dalmasso Agustin P. 
Published: August 2007

Abstract:  Background:  To induce accommodation in the hamster‐to‐rat cardiac transplantation model, in addition to cyclosporin A (CSA) to inhibit T‐cell‐mediated graft rejection, cobra venom factor (CVF) is often used to prevent complement‐mediated graft rejection. Although it is generally assumed that CVF makes accommodation possible because it inactivates the complement membrane attack complex (MAC), it is not known which complement components must be inactivated and whether complement activation products generated by CVF are also involved in the induction of accommodation. Therefore, to investigate mechanisms by which CVF contributes to accommodation, we studied induction of accommodation of hamster hearts grafted into rats with complement deficiencies of C6; these rats cannot assemble the MAC but, in contrast to CVF, retain in their native state all complement proteins that precede the MAC.Methods:  Golden Syrian hamster hearts were transplanted heterotopically into the abdomen of normocomplementemic and C6‐deficient (C6D) PVG rats. Graft rejection was determined by cessation of palpable cardiac contractions. CSA, 10 mg/kg, was administered daily to all rats. Graft survival was compared in rats given CVF (60 U/kg 1‐day pre‐transplant and 20 U/kg/day for the next 9 days), C6D rats given no CVF, normocomplementemic rats given anti‐C6 IgG or non‐immune IgG but no CVF, and C6D rats reconstituted with normocomplementemic rat serum. Total complement and C6 serum levels were measured using hemolytic assays in rat peripheral blood.Results:  We found that hamster hearts transplanted into C6D rats receiving CSA but no CVF survived long‐term, with histology typical of an accommodated heart. The accommodated hamster heart did not reconstitute C6 levels of the C6D recipient rats. Moreover, in normocomplementemic rats given anti‐C6 antibodies (abs) to induce partial C6 deficiency, accommodation also developed without administration of CVF. Accommodation of the hamster heart failed to develop in C6D rats whose complement was reconstituted by administration of normocomplementemic rat serum given before and following transplantation.Conclusions: These studies demonstrate that, in this model, inhibition of MAC‐mediated graft rejection is sufficient to allow the development of accommodation. Inactivation of C3 or other complement proteins of the alternate pathway, or the presence of complement‐derived biologically active fragments, is not needed for development of accommodation.
Granulocyte transfusions for neutropenic patients with life‐threatening infections: a single centre experience in 47 patients, who received 348 granulocyte transfusions
Authors: Ofran Y. , Avivi I. , Oliven A. , Oren I. , Zuckerman T. , Bonstein L. , Rowe J. M. , Dann E. J. 
Published: August 2007

Introduction  The role of granulocyte transfusions (GT) in patients with neutropenia‐related infections remains controversial.Materials and Methods  A retrospective analysis of 47 neutropenic patients, treated with 348 consecutive GTs for life‐threatening infections between 1999 and 2004, is presented.Results  The only grade III–IV toxicity observed in GT recipients was respiratory deterioration (n= 6, 12·8%). The overall infection‐related mortality (IRM) approached 38%. Achievement of a neutrophil count of > 700 cells per µl after at least 50% of days of GTs (n = 33, 70%) significantly correlated with reduced IRM (27·3% vs. 64·3%, P < 0·02). GT doses of > 2 × 1010 neutrophils per bag appeared to increase both neutophil and platelet counts following transfusion.Conclusion  GTs are safe and should be considered for patients with life‐threatening neutropenic infections. However, prospective randomized studies of GTs are the only way to establish the true role of GTs.
Morphology of Deep Gland of the Third Eyelid in Pig Foetuses
Authors: Klećkowska‐Nawrot J. , Dzięgiel P. 
Published: August 2007

SummaryThe morphological and histological examinations of the deep gland of the third eyelid were carried out on pig foetuses coming from the 35th, 50th, 63rd, 94th and 112th day of gestation. The morphological examinations were conducted using the method of macroscopic preparation with a forehead magnifying glass and binocular (magnification 1.5–5.0×). In order to make anatomical elements more visible, 60–80% absolute alcohol and 0.5–4% acetic acid solution were used for the examinations. For the histological examinations, the whole eyeball with developing accessory organs was collected from the pig foetuses on the 35th day of gestation. On the 50th, 63rd, 94th and 112th day of gestation only the deep gland of the third eyelid was collected. Staining with haematoxylin‐eosin and Azan method was performed. It was found during the examinations that the process of the formation of the deep gland of the third eyelid starts on the 35th day of gestation. On the 50th day of gestation, the gland cells are evenly distributed in the connective tissue stroma. On the 63rd day of gestation, the connective tissue divides the gland parenchyma into indistinct lobes composed of 6–15 lobules. On the 94th day of gestation, the gland lobes become visible; the efferent ducts are situated in the central part of the lobe. On the 112th day of gestation, the lobes are composed of a high number of lobules composed of two kinds of excretory ducts. The first type of the excretory ducts is lined with the simple cuboid epithelium whose nuclei are situated at the base of the cell. The other type of the excretory ducts is lined with the simple cuboid epithelium whose nuclei are round and arranged less or more peripherally.
Egg Cannibalism in a Facultative Polygynous Ant: Conflict for Reproduction or Strategy to Survive?
Authors: Hora Riviane R. , Poteaux Chantal , Doums Claudie , Fresneau Dominique , Fénéron Renée 
Published: August 2007

AbstractPolicing, i.e. all behaviours that prevent a nestmate from reproducing, is currently observed in social insects. It is presumed to have evolved to regulate potential conflicts generated by genetic asymmetries or to enhance colony efficiency by avoiding surplus reproductives and brood. In the ant,Ectatomma tuberculatum,individual queen fecundity was similar in monogynous and polygynous colonies issued from a Mexican population. Egg cannibalism, however, occurred in the polygynous colonies. The stealing and destruction of reproductive queen‐laid eggs involved only nestmate queens, even if they were highly related. No queen appeared to monopolize reproduction in the polygynous colonies. But, the observed value of relatedness among workers differed from the expected value, suggesting an unequal sharing of reproduction between queens. We discussed whether the cannibalism of queen‐laid eggs inE. tuberculatumresults from a competition for reproduction among queens or if this phenomenon is related to constraints on nutritional resources.
An Investigation on Strains of Clavibacter michiganensis subsp. michiganensis in North and North West of Iran
Authors: Nazari F. , Niknam G. R. , Ghasemi A. , Taghavi S. M. , Momeni H. , Torabi S. 
Published: August 2007

AbstractTomato bacterial canker disease was first reported from Urmiyeh in West Azerbaijan province in Iran. The disease causes lesion (canker), wilting and dryness of infected plants, leaf and fruit spots and the decline of the whole plant. Out of 102 isolates obtained from the fields in the major tomato producing areas of understudy regions, 98 were found Gram positive, yellow‐pigmented isolates, identified as Clavibacter michiganensis subsp. michiganensis based on the morphological and biochemical characteristics described in previous studies. Among these strains, 64 were virulent and 34 showed poor virulence. A strain of Cmm (NCPPB382) was used as a check (standard) in all steps of this study. DNA fingerprinting with repetitive‐sequence‐based PCR (rep‐PCR) (BOX primer) carried out among 11 representative strains (eight strains from West Azerbaijan, two from Golestan and one as standard). The most virulent strain was chosen as representative in each location. Dendrograms were prepared using NTSYS‐pc version 2/o2e software, unweighted pair group with arithmetic average method and simple matching similarity coefficient. According to the site of cut‐off line, three groups (clusters) with 82/5% similarity and six groups with 55% similarity were separated based on biochemical and SDS‐PAGE data, and rep‐PCR reactions respectively. Low similarity among groups (55%) can be explained as high genetic diversity among the strains. One strain of west Azerbaijan and the strains of Golestan, clustered in the same group suggesting that they may have been originated from a common source. Other strains of west Azerbaijan were clustered into different groups including II, III, IV, V and VI, suggesting the possibility of occurrence of different populations in a geographical region.
LOW CORONARY DRIVING PRESSURE IS ASSOCIATED WITH SUBENDOCARDIAL REMODELLING AND LEFT VENTRICULAR DYSFUNCTION IN AORTOCAVAL FISTULA
Authors: Guido Maria C , De Carvalho Frimm Clovis , Koike Márcia K , Cordeiro Fernanda F , Moretti Ana IS , Godoy Luiz C 
Published: August 2007

SUMMARY

The role of haemodynamic changes in left ventricular remodelling has been poorly investigated, especially in the context of volume overload cardiac hypertrophy. Low diastolic blood pressure and high left ventricular filling pressure are expected to affect coronary driving pressure negatively and thereby put in jeopardy subendocardial perfusion in particular. The consequences to global left ventricular remodelling remain undetermined. The aim of the present study was to investigate the role of coronary driving pressure in the development of subendocardial remodelling and the conceivable effects on cardiac function, using a rat model of aortocaval fistula.
Wistar rats, weighing 330–350 g, were submitted to aortocaval fistula (ACF group) or sham (control group) operations. Two haemodynamic measurements were determined following surgery, the initial measurement at week 1 and the final measurement at week 8. Cytokine expression, myeloperoxidase (MPO) activity, metalloproteinase expression and activity and fibrosis were assessed in two distinct left ventricular myocardial layers: the subendocardium (SE) and the non‐subendocardium (non‐SE).
The ACF group showed lower initial and final coronary driving pressure and lower final +dP/dt and –dP/dt compared with the control group. Multivariate analyses disclosed initial coronary driving pressure as the only haemodynamic parameter independently associated with SE fibrosis (R2 = 0.76; P < 0.0001) and with +dP/dt (R2 = 0.55; P = 0.0004) and –dP/dt (R2 = 0.91; P < 0.0001). Matrix metalloproteinase (MMP)‐2 expression and activity predominated in the SE of ACF animals, particularly in those with low coronary driving pressure. Increased levels of interleukin (IL)‐6 and IL‐1β also predominated in the SE of the ACF group. Otherwise, MPO activity and levels of tumour necrosis factor‐α and IL‐10 were similar in both groups. Final coronary driving pressure correlated with both the expression and activity of MMP‐2.
Low coronary driving pressure early in the course of ACF determines SE damage and, by this mechanism, interferes negatively in left ventricular function.
FUNCTIONS OF SK CHANNELS IN CENTRAL NEURONS
Authors: Faber ES Louise , Sah Pankaj 
Published: August 2007

SUMMARY

SK channels are small‐conductance calcium‐activated potassium channels that are widely expressed in neurons. The traditional view of the functional role of SK channels is in mediating one component of the after‐hyperpolarization that follows action potentials. Calcium influx via voltage‐gated calcium channels active during action potentials opens SK channels and the resultant hyperpolarization lowers the firing frequency of action potentials in many neurons.
Recent advances have shown that, in addition to controlling action potential firing frequency, SK channels are also important in regulating dendritic excitability, synaptic transmission and synaptic plasticity.
In accordance with their role in modulating synaptic plasticity, SK channels are also important in regulating several learning and memory tasks and may also play a role in a number of neurological disorders.
The present review discusses recent findings on the role of SK channels in central neurons.
ROLE OF MACROPHAGES IN COMPLICATIONS OF TYPE 2 DIABETES
Authors: Tesch GH 
Published: August 2007

SUMMARY

Macrophage accumulation is a feature of Type 2 diabetes and is associated with the development of diabetic complications (nephropathy, atherosclerosis, neuropathy and retinopathy). The present article reviews the current evidence that macrophages contribute to the complications of Type 2 diabetes.
Macrophage‐depletion studies in rodent models have demonstrated a causal role for macrophages in the development of diabetic complications.
Components of the diabetic milieu (high glucose, advanced glycation end‐products and oxidized low‐density lipoprotein) promote macrophage accumulation (via induction of chemokines and adhesion molecules) and macrophage activation within diabetic tissues.
Macrophages mediate diabetic injury through a variety of mechanisms, including production of reactive oxygen species, cytokines and proteases, which result in tissue damage leading to sclerosis.
A number of existing and experimental therapies can indirectly reduce macrophage‐mediated injury in diabetic complications. The present article discusses the use of these therapies, given alone and in combination, in suppressing macrophage accumulation and activity.
In conclusion, current evidence supports a critical role for macrophages in the evolution of diabetic complications. Present therapies are limited in slowing the progression of macrophage‐mediated injury. Novel strategies that are more specific at targeting macrophages may provide better protection against the development of Type 2 diabetic complications.
HUMAN HEART β‐ADRENOCEPTORS: β1‐ADRENOCEPTOR DIVERSIFICATION THROUGH ‘AFFINITY STATES’ AND POLYMORPHISM
Authors: Molenaar P , Chen L , Semmler ABT , Parsonage WA , Kaumann AJ 
Published: August 2007

SUMMARYIn atrium and ventricle from failing and non‐failing human hearts, activation of β1‐ or β2‐adrenoceptors causes increases in contractile force, hastening of relaxation, protein kinase A‐catalysed phosphorylation of proteins implicated in the hastening of relaxation, phospholamban, troponin I and C‐protein, consistent with coupling of both β1‐ and β2‐adrenoceptors to stimulatory Gsa‐protein but not inhibitory Gia‐protein.Two ‘affinity states’, namely β1Hand β1L, of the β1‐adrenoceptor exist. In human heart, noradrenaline elicits powerful increases in contractile force and hastening of relaxation. These effects are blocked with high affinity by β‐adenoceptor antagonists, including propranolol, (–)‐pindolol, (–)‐CGP 12177 and carvedilol. Some beta‐blockers, typified by (–)‐pindolol and (–)‐CGP 12177, not only block the receptor, but also activate it, albeit at much higher concentrations (approximately 2 log units) than those required to antagonize the effects of catecholamines. In human heart, both (–)‐CGP 12177 and (–)‐pindolol increase contractile force and hasten relaxation. However, the involvement of the β1‐adrenoceptor was not immediately obvious because (–)‐pindolol‐ and (–)‐CGP 12177‐evoked responses were relatively resistant to blockade by (–)‐propranolol. Abrogation of cardiostimulant effects of (–)‐CGP 12177 in β1‐/β2‐adrenoceptor double‐knockout mice, but not β2‐adrenoceptor‐knockout mice, revealed an obligatory role of the β1‐adrenoceptor. On the basis of these results, two ‘affinity states’ have been designated, the β1H‐ and β1L‐adrenoceptor, where the β1H‐adrenoceptor is activated by noradrenaline and blocked with high affinity by beta‐blockers and the β1L‐adrenoceptor is activated by drugs such as (–)‐CGP 12177 and (–)‐pindolol and blocked with low affinity by beta‐blockers such as (–)‐propranolol. The β1H‐ and β1L‐adrenoceptor states are consistent with high‐ and low‐affinity binding sites for (–)‐[3H]‐CGP 12177 radioligand binding found in cardiac muscle and recombinant β1‐adrenoceptors.There are two common polymorphic locations of the β1‐adrenoceptor, at amino acids 49 (Ser/Gly) and 389 (Arg/Gly). Their existence has raised several questions, including their role in determining the effectiveness of heart failure treatment with beta‐blockers. We have investigated the effect of long‐term maximally tolerated carvedilol administration (> 1 year) on left ventricular ejection fraction (LVEF) in patients with non‐ischaemic cardiomyopathy (mean left ventricular ejection fraction 23 ± 7%;n = 135 patients). The administration of carvedilol improved LVEF to 37 ± 13% (P < 0.005); however, the improvement was variable, with 32% of patients showing £ 5% improvement. Upon segregation of patients into Arg389Gly‐β1‐adrenoceptors, it was found that carvedilol caused a greater increase in left ventricular ejection faction in patients carrying the Arg389 allele with Arg389Arg > Arg389Gly > Gly389Gly.