bluuebunny/crossref_metadata_2025 huggingface dataset:
Obesity: attitudes of undergraduate student nurses and registered nurses
Authors: Poon Man‐Yuk , Tarrant Marie
Published: April 2009

Aim.  To investigate undergraduate student nurses’ and registered nurses’ attitudes towards obese persons and towards the management of obese patients.

Background.  Obesity is a global public health problem. Escalating rates of overweight and obesity are also taking a toll in Asian countries that have historically had much lower rates. Despite the growing prevalence of obesity worldwide, studies show that nurses and other health professionals hold negative attitudes towards obese people, which may affect the care of obese patients.

Design.  Cross‐sectional study.

Methods.  A self‐administered questionnaire was completed by 352 undergraduate student nurses and 198 registered nurses. The questionnaire consisted of the Fat Phobia Scale, the Attitudes Toward Obese Adult Patients Scale and a demographic profile. Data were analysed using descriptive statistics and student’s t‐tests.

Results.  Overall mean scores on the Fat Phobia Scale (3·53 SD 0·47) indicated average levels of fat phobia and mean scores on the Attitudes Toward Obese Adult Patients scale (2·64 SD 0·51) indicated neutral attitudes towards obese patients. Registered nurses had significantly higher levels of fat phobia and more negative attitudes than did student nurses. The majority of participants perceived that obese people liked food, overate and were shapeless, slow and unattractive. Additionally, over one‐half of participants believed that obese adults should be put on a diet while in hospital.

Conclusions.  Results of this study show that both registered nurses and student nurses have negative perceptions of obesity and are unlikely to attribute positive characteristics to obese individuals. That registered nurses hold more negative attitudes towards obese person is cause for concern.

Relevance to clinical practice.  Given the increasing prevalence of obesity and the disproportionate number of obese persons affected by many health conditions, current and future nurses should have positive professional attitudes towards obese individuals. Obesity needs to more be adequately addressed, both in basic nursing education programs and in continuing professional education for practising nurses.
Mental health nursing students' experience of stress: burdened by a heavy load
Authors: FREEBURN M. , SINCLAIR M.
Published: April 2009

This paper reports research outcomes of a study into personal stress experienced by mental health student nurses undertaking a diploma programme in Ireland. It uses a phenomenological research approach. The sample was purposive and involved in‐depth interviews with six students. The purpose of the study was to contribute to the knowledge of the impact of personal life stressors. Findings from this study focus on the following themes: event, meaning, effects, ability to move beyond the stress, influence on life and constraints and demands. Key points arising are that the stress experience does impact students' internal and external worlds, potentially lessening functioning and inhibiting growth and development. This paper presents student narratives that offer insights into their inner worlds, providing true accounts of the essence of stress for them. This knowledge has implications for lecturers, personal tutors, nurse educationalists and nursing curricula, highlighting need for more proactive approaches to the provision of guidance on professional support for students and staff. Insights derived from this study are relevant not only to mental health nurse education but also to academic staff delivering professional education programmes to healthcare practitioners in a variety of settings.
University students' suicidal thoughts and influencing factors
Authors: ENGIN E. , GURKAN A. , DULGERLER S. , ARABACI L. B.
Published: April 2009

This research was planned as a descriptive study for the purpose of examining the suicidal thoughts of first‐year university students and the factors that might affect them. The research was conducted with the participation of first‐year students (class of 1992) at Ege University between January 2003 and October 2004. The research data were collected on a form prepared by the researcher to determine the university students' socio‐demographic characteristics and their suicidal thoughts, the trait anger, expression of anger inventory and the brief symptom inventory. It was determined that 2.4% of the students had suicidal thoughts, and 11.2% of the students had previously attempted suicide. The risk factors of the students' suicidal thoughts were determined to be issues of gender, school problems, family relationships, anger expression, somatization, hostility, psychotic symptoms, phobic anxiety, anxiety disorder and interpersonal sensitivity.
In vitro characterization of Inocutis jamaicensis and experimental inoculation of Eucalyptus globulus standing trees
Authors: Lupo S. , Pérez A. , Martínez S. , Simeto S. , Rivas F. , Bettucci L.
Published: April 2009

Lesions of variable size, associated with the hymenomycete Inocutis jamaicensis, a white‐rot fungus, have been observed on the stems of Eucalyptus globulus trees in Uruguay. The aim of this study was to evaluate some ecophysiological characteristics of I. jamaicensis and assess its ability to colonize E. globulus trees of two different seed origins (Geeveston and Jeeralang) and the clone, 334‐1‐AR, obtained by micropropagation (ENCE, Spain). The growth of an I. jamaicensis isolate (MVHC11379) was evaluated at 25°C in a medium with a water potential of 0 (Ψ = 0). The growth rate did not vary significantly with a growth medium pH of between 4 and 7. I. jamaicensis showed no growth at either 5 or 37°C at any pH or Ψ tested. Weight loss of heartwood and sapwood of different plant provenances inoculated with I. jamaicensis under laboratory conditions was evaluated, and significant differences observed. Lignin‐modifying enzyme activity was evaluated in culture medium with or without E. globulus sawdust as substrate or inducer. Laccase activity was observed with sawdust and manganese peroxidase activity with and without sawdust. Only slight activity of aryl‐alcohol oxidase and lignin peroxidase was detected without sawdust. Experimental inoculation with I. jamaicensis of 3‐year‐old Geeveston and Jeeralang, and of 4‐year‐old 334‐1‐AR stems, resulted in successful fungal colonization of 56% of the 334‐1‐AR, 50% of Geeveston and 25% of Jeeralang trees. Only the heartwood was decayed. In 334‐1‐AR, the rotted wood was delimited by a reaction zone. Wood characteristics and the ability of I. jamaicensis to overcome the chemical reactions in the tree could partially explain differences in susceptibility to the fungus among provenances observed under natural and laboratory conditions.
An in vitro method for screening Colletotrichum gloeosporioides as a biological control agent for western hemlock dwarf mistletoe
Authors: Askew S. E. , Shamoun S. F. , Van Der Kamp B. J.
Published: April 2009

An in vitro system using detached western hemlock branches infected with dwarf mistletoe was developed to screen the virulence of five isolates of Colletotrichum gloeosporioides, a hyperparasite of dwarf mistletoe shoots and berries. Detached branches infected with dwarf mistletoe were placed in nutrient‐saturated rock‐wool blocks and mistletoe shoots were inoculated with a conidial suspension of C. gloeosporioides. One month after inoculation, lesions on mistletoe stems and berries were well developed. Infection levels for individual isolates varied from 40% to 60% of shoots and 60% to 80% of berries. Significant differences were found between the isolates and control (p = 0.02 and 0.001, respectively) while no differences were noted between the isolates for both the shoots and berries. Parallel inoculation of mistletoe shoots detached from hemlock branches on moist filter paper and in rock‐wool blocks failed because these shoots deteriorated rapidly, fragmenting into segments within a week. This in vitro test may provide an alternative method for rapid screening of potentially virulent C. gloeosporioides isolates.
Comparison of endoscopic findings with symptom assessment systems (FSSG and QUEST) for gastroesophageal reflux disease in Japanese centres
Authors: Danjo Akiko , Yamaguchi Kanako , Fujimoto Kazuma , Saitoh Toshihito , Inamori Masahiko , Ando Takashi , Shimatani Tomohiko , Adachi Kyoichi , Kinjo Fukunori , Kuribayashi Shiko , Mitsufuji Shoji , Fujiwara Yasuhiro , Koyama Shigeki , Akiyama Junichi , Takagi Atsushi , Manabe Noriaki , Miwa Hiroto , Shimoyama Yasuyuki , Kusano Motoyasu
Published: March 2009

Background and Aim:  We compared endoscopic findings of the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), a written questionnaire developed in Japan, to that for the questionnaire for the diagnosis of reflux esophagitis (QUEST) for the diagnosis of reflux esophagitis.

Methods:  We registered 475 patients with untreated symptoms of upper abdominal pain (male/female: 252/223, average age 52.4 ± 17.8 years). Subjects were assessed first with the FSSG and QUEST questionnaires, then by endoscopy, before allocation to a gastric ulcer (GU), duodenal ulcer (DU), gastroesophageal reflux disease (GERD) or functional dyspepsia (FD) group.

Results:  On the basis of the endoscopic findings the diagnoses for the 475 subjects were as follows: FD 52.2%, DU 7.6%, GU 7.8%, and GERD 32.4% (Grade M 10.1%, Grade A + B 20.2%, Grade C + D 2.3%). There was no difference between the FSSG and QUEST in sensitivity, specificity or accuracy for any condition. The FSSG score rose with increasing endoscopic severity of GERD, but there was no correlation between the QUEST score and endoscopic severity. The FSSG total score was inferior to QUEST in terms of distinguishing GERD from other conditions, but when only the questions relating to reflux symptoms were used, the FSSG was able to distinguish GERD from other conditions as well as QUEST.

Conclusions:  The FSSG score reflects the severity of the endoscopic findings of GERD.
Copy number estimation algorithms and fluorescencein situhybridization to describe copy number alterations in human tumors
Authors: Suzuki Masaya , Nagura Kiyoko , Igarashi Hisaki , Tao Hong , Midorikawa Yutaka , Kitayama Yasuhiko , Sugimura Haruhiko
Published: March 2009

The platforms of high‐resolution genetic analysis of human tumors have become popular, and several copy number estimation algorithms have been applied to the data generated by single‐nucleotide polymorphism microarrays. Although comparisons have been made between several different platforms or methodologies, there has never been a robust comparison of different copy number estimation algorithms, and the validity of the estimations in comparison with multiple fluorescencein situhybridization (FISH) data in tumors has rarely been addressed. In the present study the dataset that the Affymetrix 250KNsparray generated in two cancer cases was used to compare the two widely used algorithms for estimating copy number alterations (CNA): the genotyping microarray‐based copy number variation (CNV) analysis (GEMCA) algorithm and the copy number analyzer for Affymetrix Genechip mapping (CNAG) algorithm. Considerable differences were noticed between the estimations by these two algorithms, because of the difference in the formula used to calculate the threshold values. Both algorithms yielded highly consistent data with the FISH results, but CNAG was more stringent for detecting loss. There were areas in which both algorithms provided gains, but FISH showed no change. It will be interesting to pursue the reasons for these remaining discrepancies.
Molecular diversity of deep short‐axon cells of the rat main olfactory bulb
Authors: Eyre Mark D. , Kerti Katalin , Nusser Zoltan
Published: March 2009

Local circuit GABAergic interneurons comprise the most diverse cell populations of neuronal networks. Interneurons have been characterized and categorized based on their axo‐somato‐dendritic morphologies, neurochemical content, intrinsic electrical properties and their firing in relation to in‐vivo population activity. Great advances in our understanding of their roles have been facilitated by their selective identification. Recently, we have described three major subtypes of deep short‐axon cells (dSACs) of the main olfactory bulb (MOB) based on their axo‐dendritic distributions and synaptic connectivity. Here, we investigated whether dSACs also display pronounced molecular diversity and whether distinct dSAC subtypes selectively express certain molecules. Multiple immunofluorescent labeling revealed that the most commonly used molecular markers of dSACs (e.g. vasoactive intestinal polypeptide, calbindin and nitric oxide synthase) label only very small subpopulations (< 7%). In contrast, voltage‐gated potassium channel subunits Kv2.1, Kv3.1b, Kv4.3 and the GABAA receptor α1 subunit are present in 70–95% of dSACs without showing any dSAC subtype‐selective expression. However, metabotropic glutamate receptor type 1α mainly labels dSACs that project to the glomerular layer (GL‐dSAC subtype) and comprise ∼20% of the total dSAC population. Analysing these molecular markers with stereological methods, we estimated the total number of dSACs in the entire MOB to be ∼13 500, which is around a quarter of the number of mitral cells. Our results demonstrate a large molecular heterogeneity of dSACs and reveal a unique neurochemical marker for one dSAC subtype. Based on our results, dSAC subtype‐specific genetic modifications will allow us to decipher the role of GL‐dSACs in shaping the dynamic activity of the MOB network.
Abnormal screening glucose challenge test in pregnancy and future risk of diabetes in young women
Authors: Retnakaran R. , Shah B. R.
Published: April 2009

Aims  Pregnant women commonly undergo screening for gestational diabetes mellitus (GDM) using a 50‐g glucose challenge test (GCT), followed by a diagnostic oral glucose tolerance test (OGTT) in those women in whom the GCT is abnormal. Although it has long been recognized that GDM is associated with subsequent Type 2 diabetes, it has recently emerged that any degree of abnormal antepartum glucose homeostasis predicts an increased risk of postpartum glucose intolerance. Thus, in this context, we sought to determine whether women who have a pregnancy complicated by an abnormal GCT, but who do not have GDM, are at increased risk of subsequent diabetes, compared with their peers with an abnormal GCT.

Methods  A population‐based, retrospective cohort study was conducted. Women referred for an antepartum OGTT indicative of an abnormal GCT (n = 15 381), but without GDM, were matched (for age, region, socioeconomic status, and year of delivery) with up to four other women without such referral (n = 61 237). The two cohorts were followed over a median 6.4 years for the development of diabetes.

Results  The rate of incident diabetes was 5.04 cases per 1000 person‐years in the cohort of women who underwent an antepartum OGTT, compared with 1.74 cases per 1000 person‐years in women without an OGTT. The hazard ratio for subsequent diabetes in women with an antepartum OGTT was 2.56 (95% confidence interval 2.28, 2.87) (P < 0.0001).

Conclusions  Even in the absence of GDM, abnormal screening GCT in pregnancy is associated with an increased future risk of diabetes in young women.
Metabolic syndrome: collapsing under its own weight?
Authors: Preiss D. , Sattar N.
Published: April 2009

Invited counterview to article by Cameron AJ, Zimmet PZ, Shaw JE, Alberti KGMM. The metabolic syndrome: in need of a global mission statement. Diabet Med 2009;
26: 306–309
The Y402H variant of complement factor H is associated with age‐related macular degeneration but not with diabetic retinal disease in the Go‐DARTS study
Authors: Doney A. S. F. , Leese G. P. , Olson J. , Morris A. D. , Palmer C. N. A.
Published: April 2009

Aims  The Y402H variant of complement factor H (CFH) is associated with risk of age‐related macular degeneration (ARMD). In common with ARMD, diabetic retinal disease also appears to involve complement activation. The aim was to investigate the impact of Y402H on both retinal pathologies in patients with Type 2 diabetes (T2DM) undergoing systematic eye screening.

Methods  Patients with T2DM (n = 2350) were genotyped for the CFH Y402H variant. The association of genotype with retinal disease was determined in both retrospective and prospective models.

Results  The retrospective study demonstrated that the HH genotype was associated with an age‐adjusted odds ratio of 7.4 for ARMD (P = 2.9 × 10−11). In a longitudinal study in the disease‐free cohort, the age‐adjusted hazard ratio was 2.8 (P = 2.4 × 10−7). The life‐time hazard ratio was 3.4 (P = 2.1 × 10−16). We found no association of Y402H with development of referable diabetic retinal disease.

Conclusion  The ARMD‐associated Y402H variant in CFH does not appear to be associated with diabetic retinal disease, although complement activation is involved in the pathoaetiology of both conditions.
A Study of the Role Played by Manufacturing Strategic Objectives and Capabilities in Understanding the Relationship between Porter's Generic Strategies and Business Performance
Authors: González‐Benito Javier , Suárez‐González Isabel
Published: March 2009

An appropriate alignment between business strategy, manufacturing strategic objectives and manufacturing capabilities reportedly influences business performance positively. However, few papers empirically analyse this proposition for the case of Porter's generic strategies of cost leadership and differentiation, and none jointly considers all four elements. This paper integrates strategies, capabilities and performance in a single model and proposes that both manufacturing competitive priorities and capabilities, articulated in terms of cost and flexibility, are essential for explaining the link between generic business strategies and business commercial and financial performance. Within this analytic framework, we test whether companies that emphasize one business strategy rather than another achieve a better alignment and superior performance. The analyses conducted with a sample of 148 Spanish manufacturers provide general support for these propositions and contribute to a deeper understanding of the role played by functional strategies in understanding the outcomes of business strategy.
Statistical Issues in the Assessment of Health Outcomes in Children: A Methodological Review
Authors: Lancaster Gillian A.
Published: April 2009

The lack of outcome measures that are validated for use on children limits the effectiveness and generalizability of paediatric health care interventions. Statistical epidemiology is a broad concept encompassing a wide range of useful techniques for use in child health outcome assessment and development. However, the range of techniques that are available is often confusing and prohibits their adoption. In the paper an overview of methodology is provided within the paediatric context. It is demonstrated that in many cases assessment can be performed relatively straightforwardly by using standard statistical techniques, although sometimes more sophisticated techniques are required. Examples of both physiological and questionnaire-based outcomes are given. The usefulness of these techniques is highlighted for achieving specific objectives and ultimately for achieving methodological rigour in clinical outcome studies that are performed in the paediatric population.
Using Relative Utility Curves to Evaluate Risk Prediction
Authors: Baker Stuart G. , Cook Nancy R. , Vickers Andrew , Kramer Barnett S.
Published: April 2009

Because many medical decisions are based on risk prediction models that are constructed from medical history and results of tests, the evaluation of these prediction models is important. This paper makes five contributions to this evaluation: the relative utility curve which gauges the potential for better prediction in terms of utilities, without the need for a reference level for one utility, while providing a sensitivity analysis for misspecification of utilities, the relevant region, which is the set of values of prediction performance that are consistent with the recommended treatment status in the absence of prediction, the test threshold, which is the minimum number of tests that would be traded for a true positive prediction in order for the expected utility to be non-negative, the evaluation of two-stage predictions that reduce test costs and connections between various measures of performance of prediction. An application involving the risk of cardiovascular disease is discussed.
Is the ‘Trade‐off Hypothesis’ Worth Trading For?
Authors: PHELAN MARK , SARKISSIAN HAGOP
Published: March 2009

Abstract:  Recently, the experimental philosopher Joshua Knobe has shown that the folk are more inclined to describe side effects as intentional actions when they bring about bad results. Edouard Machery has offered an intriguing new explanation of Knobe’s work—the ‘trade‐off hypothesis’—which denies that moral considerations explain folk applications of the concept of intentional action. We critique Machery’s hypothesis and offer empirical evidence against it. We also evaluate the current state of the debate concerning the concept of intentionality, and argue that, given the number of variables at play, any parsimonious account of the relevant data is implausible.
Dopaminergic treatment is associated with decreased body weight in patients with Parkinson’s disease and dyskinesias
Authors: Bachmann C. G. , Zapf A. , Brunner E. , Trenkwalder C.
Published: April 2009

Background and purpose:  Several studies suggested that patients with advanced Parkinson’s disease (PD) showed a too low body weight when compared with age‐matched, healthy subjects. We aimed to investigate whether PD patients with dyskinesias display body weight alterations and to observe any correlations between medication and other putative determinants.

Methods:  Charts of 166 PD patients with fluctuations and dyskinesias, admitted within 6 months to a German movement disorders clinic, were investigated for body mass index (BMI), age at onset, disease duration, Unified Parkinson’s Disease Rating Scale motor score, eating coordination and medication.

Results:  Analysis showed that 4.2% of PD patients were underweight (BMI < 18.5 kg/m2), 46.4% were normal (BMI > 18.5–25 kg/m2), 33.7% were overweight (BMI > 25–30 kg/m2), 15.7% were obese (BMI > 30 kg/m2). Daily levodopa dosage per kg and total dopaminergic dosage per kg body weight were negatively correlated with BMI. Overall, patients’ BMI had not significantly changed within 2 years of follow‐up.

Conclusions:  In sum, advanced PD patients showed a reduced BMI when compared with a control population obtained from an age‐matched group taken from a survey of the German Federal Office for Statistics. Our findings indicate that patients with a lower BMI received a higher cumulative levodopa dosage and that levodopa may be responsible for weight loss in PD.
Epidemiological and immunological profile of muscle‐specific kinase myasthenia gravis in Greece
Authors: Tsiamalos P. , Kordas G. , Kokla A. , Poulas K. , Tzartos S. J.
Published: April 2009

Objectives:  The purposes of this study were to determine the epidemiological characteristics of muscle‐specific kinase‐myasthenia gravis (MuSK‐MG) in Greece and the IgG subclass of the anti‐MuSK antibodies.

Methods:  This population‐based study was performed on MuSK‐MG patients in Greece between 1 January 1986 and 30 June 2006. Epidemiological and clinical data for 33 patients were collected. In addition, the distribution of anti‐MuSK IgG autoantibody subclasses in the sera of 14 patients was determined by immunoprecipitation.

Results:  The average annual incidence was 0.32 patients/million population/year. On 1st July 2006, there were 33 prevalent cases, giving a point prevalence rate of 2.92/million (women 4.56 and men 1.25). In females, onset of MuSK‐MG occurred after the age of 30, whilst, in males, the disease appears in any decade. The female:male incidence ratio was 3.33:1, whilst the prevalence ratio was 3.65:1. Most patients presented with involvement of the facial and bulbar muscles. Amongst about 800 MG patients seropositive for antibodies against either the AChR or MuSK, one patient was found to be seropositive for anti‐MuSK antibodies and ambiguous for anti‐acetylcholine receptor (anti‐AChR) antibodies. The vast majority of anti‐MuSK antibodies were IgG4, whilst total IgG4 levels in these patients were similar to those in two healthy controls.

Conclusions:  The incidence and prevalence of MuSK‐MG in Greece are amongst the highest reported previously for other countries. MuSK‐MG in Greece affects both sexes, but mainly females. The main epidemiological indices were calculated. The vast majority of anti‐MuSK antibodies were IgG4.
On‐again/off‐again dating relationships: How are they different from other dating relationships?
Authors: DAILEY RENÉ M , PFIESTER ABIGAIL , JIN BORAE , BECK GARY , CLARK GRETCHEN
Published: March 2009

This article explores the understudied yet prevalent phenomenon of on‐again/off‐again (on‐off) dating relationships. Study 1 (N= 445 U.S. college students) showed that almost two thirds of participants had experienced an on‐off relationship. Analyses of open‐ended responses about relationship experiences showed on‐off partners were less likely to report positives (e.g., love and understanding from partners) and more likely to report negatives (e.g., communication problems, uncertainty) than partners who had not broken up and renewed. Study 2 (N= 236), employing quantitative measures, substantiated these findings and further showed a greater number of renewals was associated with greater negatives and fewer positives. Results highlight the need for further investigation regarding on‐off relationships, and theories potentially useful in explaining these relationships are discussed.
Piceatannol, a derivative of resveratrol, moderately slows INa inactivation and exerts antiarrhythmic action in ischaemia‐reperfused rat hearts
Authors: Chen Wen‐Pin , Hung Li‐Man , Hsueh Chia‐Hsiang , Lai Ling‐Ping , Su Ming‐Jai
Published: April 2009

Background and purpose:  Piceatannol is more potent than resveratrol in free radical scavenging in association with antiarrhythmic and cardioprotective activities in ischaemic‐reperfused rat hearts. The present study aimed to investigate the antiarrhythmic efficacy and the underlying ionic mechanisms of piceatannol in rat hearts.

Experimental approach:  Action potentials and membrane currents were recorded by the whole‐cell patch clamp techniques. Fluo‐3 fluorimetry was used to measure cellular Ca2+ transients. Antiarrhythmic activity was examined from isolated Langendorff‐perfused rat hearts.

Key results:  In rat ventricular cells, piceatannol (3–30 µmol·L−1) prolonged the action potential durations (APDs) and decreased the maximal rate of upstroke (Vmax) without altering Ca2+ transients. Piceatannol decreased peak INa and slowed INa inactivation, rather than induced a persistent non‐inactivating current, which could be reverted by lidocaine. Resveratrol (100 µmol·L−1) decreased peak INa without slowing INa inactivation. The inhibition of peak INa or Vmax was associated with a negative shift of the voltage‐dependent steady‐state INa inactivation curve without altering the activation threshold. At the concentrations more than 30 µmol·L−1, piceatannol could inhibit ICa,L, Ito, IKr, Ca2+ transients and Na+‐Ca2+ exchange except IK1. Piceatannol (1–10 µmol·L−1) exerted antiarrhythmic activity in isolated rat hearts subjected to ischaemia‐reperfusion injury.

Conclusions and implications:  The additional hydroxyl group on resveratrol makes piceatannol possessing more potent in INa inhibition and uniquely slowing INa inactivation, which may contribute to its antiarrhythmic actions at low concentrations less than 10 µmol·L−1.
T‐817MA, a neurotrophic agent, ameliorates the deficits in adult neurogenesis and spatial memory in rats infused i.c.v. with amyloid‐β peptide
Authors: Kimura Tatsuo , Hong Nguyen Phuong Thi , Ho Son Anh , Tran Anh Hai , Ono Taketoshi , Nishijo Hisao
Published: April 2009

Background and purpose:  Adult neurogenesis occurs throughout life in the subgranular zone and the dentate gyrus of the hippocampus. Deficient neurogenesis may be responsible for deficient hippocampal functions in neurodegenerative disorders such as Alzheimer's disease (AD). T‐817MA [1‐{3‐[2‐(1‐Benzothiophen‐5‐yl)ethoxy] propyl}‐3‐azetidinol maleate] is a newly synthesized agent for AD treatment with neuroprotective effects against toxicity from amyloid‐β peptide (Aβ) and actions promoting neurite outgrowth in vitro. Furthermore, systemic administration of T‐817MA ameliorated cognitive dysfunctions caused by neurodegeneration in a rat model of AD, induced by intracerebroventricular (i.c.v.) infusion of Aβ. The present study investigated quantitative relationships between spatial memory performance in Aβ‐infused rats and hippocampal neurogenesis, and the effects of T‐817MA on neuronal proliferation in vivo.

Experimental approach:  Seven weeks after infusion of Aβ (peptide 1–40; 300 pmol·day−1; i.c.v.), rats were tested in a place learning task in which they were required to alternately visit two reward places in an open field to obtain intracranial self‐stimulation as rewards.

Key results:  Rats given Aβ infusions for 10 weeks displayed spatial memory impairments and a decrease in neurogenesis compared with those infused with vehicle. Treatment of the Aβ‐infused rats with T‐817MA (8.4 mg·kg−1·day−1, p.o.) significantly increased hippocampal neurogenesis and ameliorated spatial learning impairments. Furthermore, spatial learning in the task was significantly correlated with neurogenesis.

Conclusions and implications:  These results suggest that defective hippocampal neurogenesis is a new target for AD treatment. The neurotrophic compound T‐817MA increased hippocampal neurogenesis in an AD model and might be useful for treatment of AD patients.
Zoledronic acid induces formation of a pro‐apoptotic ATP analogue and isopentenyl pyrophosphate in osteoclasts in vivo and in MCF‐7 cells in vitro
Authors: Räikkönen Johanna , Crockett Julie C , Rogers Michael J , Mönkkönen Hannu , Auriola Seppo , Mönkkönen Jukka
Published: April 2009

Background and purpose:  Bisphosphonates (BPs) are highly effective inhibitors of bone resorption. Nitrogen‐containing bisphosphonates (N‐BPs), such as zoledronic acid, induce the formation of a novel ATP analogue (1‐adenosin‐5′‐yl ester 3‐(3‐methylbut‐3‐enyl) ester triphosphoric acid; ApppI), as a consequence of the inhibition of farnesyl pyrophosphate synthase and the accumulation of isopentenyl pyrophosphate (IPP). ApppI induces apoptosis, as do comparable metabolites of non‐nitrogen‐containing bisphosphonates (non‐N‐BPs). In order to further evaluate a pharmacological role for ApppI, we obtained more detailed data on IPP/ApppI formation in vivo and in vitro. Additionally, zoledronic acid‐induced ApppI formation from IPP was compared with the metabolism of clodronate (a non‐N‐BP) to adenosine 5′(β,γ‐dichloromethylene) triphosphate (AppCCl2p).

Experimental approach:  After giving zoledronic acid in vivo to rabbits, IPP/ApppI formation and accumulation was assessed in isolated osteoclasts. The formation of ApppI from IPP was compared with the metabolism of clodronate in MCF‐7 cells in vitro. IPP/ApppI and AppCCl2p levels in cell extracts were analysed by mass spectrometry.

Key results:  Isopentenyl pyrophosphate/ApppI were formed in osteoclasts in vivo, after a single, clinically relevant dose of zoledronic acid. Furthermore, exposure of MCF‐7 cells in vitro to zoledronic acid at varying times and concentrations induced time‐ and dose‐dependent accumulation of IPP/ApppI. One hour pulse treatment was sufficient to cause IPP accumulation and subsequent ApppI formation, or the metabolism of clodronate into AppCCl2p.

Conclusions and implications:  This study provided the first conclusive evidence that pro‐apoptotic ApppI is a biologically significant molecule, and demonstrated that IPP/ApppI analysis is a sensitive tool for investigating pathways involved in BP action.
Current status and challenges of cytokine pharmacology
Authors: Zídek Z , Anzenbacher P , Kmoníčková E
Published: April 2009

The major concern of pharmacology about cytokines has originated from plentiful data showing association between gross changes in their production and pathophysiological processes. Despite the enigmatic role of cytokines in diseases, a number of them have become a subject of cytokine and anti‐cytokine immunotherapies. Production of cytokines can be influenced by many endogenous and exogenous stimuli including drugs. Cells of the immune system, such as macrophages and lymphocytes, are richly endowed with receptors for the mediators of physiological functions, such as biogenic amines, adenosine, prostanoids, steroids, etc. Drugs, agonists or antagonists of these receptors can directly or indirectly up‐ and down‐regulate secretion of cytokines and expression of cytokine receptors. Vice versa, cytokines interfere with drug pharmacokinetics and pharmacodynamics through the interactions with cytochrome P450 and multiple drug resistance proteins. The aim of the review is to encourage more intensive studies in these fields of cytokine pharmacology. It also outlines major areas of searching promising candidates for immunotherapeutic interventions.
Transnational Human Rights Networks
Authors: Tang Min
Published: April 2009

‘Transnational human rights networks' has become a hot research topic for international human rights studies in recent years. It mainly documents and theorizes the transnationalization or internationalization of human rights norms and practices during the last several decades. It began as a distinctive field of research scholarship and has grown to challenge the traditional approaches to international studies. This review introduces the major tenets of this field and, without downplaying their contribution to international studies, it also tries to point out several problems in the conceptualization, theorization and methodology of the current studies on human rights networks. This critical analysis is followed by some suggestions for future studies.
Polymorphism of the MDR1/ABCB1 C3435T drug‐transporter and resistance to anticonvulsant drugs: A meta‐analysis
Authors: Bournissen Facundo Garcia , Moretti Myla E. , Juurlink David N. , Koren Gideon , Walker Mugabe , Finkelstein Yaron
Published: April 2009

Background:  Approximately one‐third of patients with epilepsy patients have recurrent seizures despite therapy. It has been suggested that therapeutic failure is associated with high expression of the multidrug efflux ABCB1 (MDR1) drug‐transporter; specifically, that patients with the 3435CC genotype have higher efflux of anticonvulsants out of brain tissue, with correspondingly lower concentrations in the central nervous system.

Methods:  We conducted a meta‐analysis to examine the association between MDR1 polymorphisms and the response to anticonvulsants. We included all published studies until September 2007, in which patients with responsive and unresponsive seizure disorders underwent genotyping for ABCB1 C3435T. Individual and summary odds ratios were calculated using a random effects model. A secondary analysis was also performed, stratifying the studies by their ethnic distribution to account for genetic heterogeneity. We also performed a cumulative analysis by date of publication for the included studies using a random effects model.

Results:  We identified 11 case‐control studies involving 3,371 patients (1,646 patients with drug‐resistant epilepsy and 1,725 controls). We identified no significant association between anticonvulsant drug resistance and MDR1 polymorphism [odds ratio 1.15; 95% confidence interval (CI) 0.78–1.70; p = 0.48). Subanalysis of studies according to ethnicity yielded similar findings [European cohort: OR = 1.31; 95% CI 0.89–1.94, p = 0.18; Asian cohort: OR = 0.99; 95% CI 0.51–1.89, p = 0.96).

Conclusions:  We found no association between ABCB1 genotype and response to anticonvulsant drugs. At the present time, genetic typing for MDR1 polymorphism is not warranted for patients with drug‐resistant epilepsy.
Structural, Mechanical, and Reactivity Properties of Tricalcium Aluminate Using First‐Principles Calculations
Authors: Manzano Hegoi , Dolado Jorge S. , Ayuela Andrés
Published: March 2009

Although tricalcium aluminate (C3A) is one of the most important components of Portland cement, neither its reactivity nor its elastic moduli tensor have been fully determined yet. This work aims to shed some insights on these questions by means of ab‐initio simulations. First our simulations have reproduced the details of its crystalline structure. Second, we have computed the full elastic moduli tensor of C3A, where we found that our value for the Young modulus (E=138.7 GPa) is in agreement with the values obtained by nanoindentation measurements. Finally, we have identified which atoms and sites are more suitable to suffer chemical attacks.
Fabrication of Blanket‐Like Assembled ZnO Nanowhiskers Using an Aqueous Solution
Authors: Hu Xiulan , Masuda Yoshitake , Ohji Tatsuki , Kato Kazumi
Published: March 2009

Blanket‐like assembled ZnO nanowhiskers were fabricated using a freestanding ZnO nanoparticle layer by an aqueous solution deposition. X‐ray diffraction and field emission scanning electron microscopy clarified the crystalline phase, orientation, morphology, and microstructure. Thermal treatment of the zinc acetate dihydrate layer resulted in the formation and delamination of the ZnO nanoparticle layer on the glass substrate. The growth habits of ZnO crystals resulted in the growth of ZnO nanowhiskers preferentially orientated along the direction of the c‐axis on the whole surface of the freestanding ZnO nanoparticle layer by heterogeneorous nucleation and growth. The hierarchical‐structured blanket‐like ZnO nanowhisker assemblies can be utilized for dye‐sensitive solar cells and gas sensors because of their high surface‐to‐volume ratio.
Disentangling regional and local tree diversity in the Amazon
Authors: Stropp Juliana , Ter Steege Hans , Malhi Yadvinder ,   ATDN,   RAINFOR
Published: April 2009

We analyzed the most extensive data set of tree inventory plots spread over the complete Amazon basin and Guiana shield. We aimed to separate the regional and local tree alpha‐diversity to investigate the drivers of diversity at the relevant scale. Our results are consistent with the partitioning of total tree alpha‐diversity into regional and local components, which are controlled by evolutionary‐ and ecological processes, respectively. Regional diversity is correlated with palaeo‐climatic stability (31%), and long‐term large‐scale ecosystem dynamics (14%), as represented by the age of the geological formation. Both mechanisms contribute to high diversity in the central to western Amazon. Actual rainfall seasonality is correlated with regional tree diversity to a certain extent (19%), but we argue that this is of little consequence for the evolutionary drivers of the regional species pool. Frequency of disturbance is the main process driving local diversity, although its explanatory power is relatively small (17%).
Individualistic vs community modelling of species distributions under climate change
Authors: Baselga Andrés , Araújo Miguel B.
Published: April 2009

Studies investigating the consequences of future climate changes on species distributions usually start with the assumption that species respond to climate changes in an individualistic fashion. This assumption has led researchers to use bioclimate envelope models that use present climate‐range relationships to characterize species’ limits of tolerance to climate, and then apply climate‐change scenarios to enable projections of altered species distributions. However, there are techniques that combine climate variables together with information on the composition of assemblages to enable projections that are expected to mimic community dynamics. Here, we compare, for the first time, the performance of GLM (generalized linear model) and CQO (canonical quadratic ordination; a type of community‐based GLM) for projecting distributions of species under climate change scenarios. We found that projections from these two methods varied both in terms of accuracy (GLM providing generally more accurate projections than CQO) and in the broad diversity patterns yielded (higher species richness values projected with CQO). Model outputs were also affected by species‐specific traits, such as species range size and species geographical positions, supporting the view that methods are sensitive to different degrees of equilibrium of species distributions with climate. This study reveals differences in projections between individual‐ and community‐based approaches that require further scrutiny, but it does not find support for unsupervised use community‐based models for investigating climate change impacts on species distributions. Reasons for this lack of support are discussed.
Behavioral intermittence, Lévy patterns, and randomness in animal movement
Authors: Bartumeus F.
Published: March 2009

The recent debate on both the existence and the cause of fractal (Lévy) patterns in animal movement resonates with much deeper and richer problems in movement ecology: (1) establishing mechanistic links between animal behavior and statistical patterns of movement, and (2) understanding what is the role of randomness (stochasticity) in animal motion. Here, the idea of behavioral intermittence is shown to be crucial to establish mechanistic connections between the behavior of organisms and the statistical properties they generate when moving. Attention is drawn to the fact that some random walk modeling procedures can impair the identification of intermittent biological mechanisms which could govern major statistical properties of movement. This fact, together with some misconceptions and prejudices regarding the role of randomness in animal motion may explain why stochastic processes have been disregarded as a potential source of adaptation in animal movement. In the near future, the advances in biotelemetry together with a more explicit consideration of behavioral intermittence, and the development of novel random walk approaches, could help us to set up the bases for a landscape‐level behavioral ecology.
Testing dynamic variance‐sensitive foraging using individual differences in basal metabolic rates of zebra finches
Authors: Mathot Kimberley J. , Godde Sophie , Careau Vincent , Thomas Donald W. , Giraldeau Luc‐Alain
Published: March 2009

Social foragers can alternate between searching for food (producer tactic), and searching for other individuals that have located food in order to join them (scrounger tactic). Both tactics yield equal rewards on average, but the rewards generated by producer are more variable. A dynamic variance‐sensitive foraging model predicts that social foragers should increase their use of scrounger with increasing energy requirements and/or decreased food availability early in the foraging period. We tested whether natural variation in minimum energy requirements (basal metabolic rate or BMR) is associated with differences in the use of producer–scrounger foraging tactics in female zebra finchesTaeniopygia guttata. As predicted by the dynamic variance‐sensitive model, high BMR individuals had significantly greater use of the scrounger tactic compared with low BMR individuals. However, we observed no effect of food availability on tactic use, indicating that female zebra finches were not variance‐sensitive foragers under our experimental conditions. This study is the first to report that variation in BMR within a species is associated with differences in foraging behaviour. BMR‐related differences in scrounger tactic use are consistent with phenotype‐dependent tactic use decisions. We suggest that BMR is correlated with another phenotypic trait which itself influences tactic use decisions.
Febrile seizures
Authors: Østergaard John R
Published: April 2009

Febrile seizures (FS) are the most common seizure disorder in childhood, affecting 2–5% of children between the ages of 3 and 60 months. Differentiation of FS from acute symptomatic seizures secondary to central nervous system infection is essential. Those with a focal onset, prolonged duration or which occur more than once within the same febrile illness are considered complex and have an increase in risk of subsequent epilepsy development. The vast majority of febrile convulsions are simple, lasting only a few minutes and without need of drug intervention. They have an excellent outcome with no increased risk of decline in IQ, subsequent epilepsy or increased mortality. Febrile seizure can recur, and as it often is a frightening and anxiety‐provoking event for parents and caregivers, an understanding of the natural history and prognosis should enable the physician to reassure the parents providing an appropriate counselling and reassurance.

Conclusion: Febrile seizure can recur, and as it often is a frightening and anxiety‐provoking event for parent and caregivers. An understanding of the natural history and prognosis should enable the physician to reassure the parents providing an appropriate counselling and reassurance.
Educational strategy to reduce medication errors in a neonatal intensive care unit
Authors: Campino Ainara , Lopez‐Herrera Maria Cruz , Lopez‐de‐Heredia Ion , Valls‐i‐Soler Adolf
Published: April 2009

Objective: We aimed to evaluate the effect of a comprehensive preventive educational strategy on the number and type of drug errors in the prescription process in a regional neonatal intensive care unit (NICU).

Design: Medication errors during prescription were recorded in a 41 bed, level III regional neonatal unit by a pharmacist. Data were retrieved from handwritten doctor's orders and introduced at bedsite into an e‐database. Each prescription, not related to enteral and parenteral nutrition and blood products, was evaluated for dosage, units, route and dosing interval. The study was developed in three phases: pilot phase to know the baseline drug error rate and estimate sample size; pre‐intervention (4182 drug orders reviewed); and post‐intervention seven months after a comprehensive preventive educational intervention consisting sessions about drug errors and study's aims was implemented.

Results: After the preventive educational intervention was implemented, the prescription error rate and the percentage of registers with one or more incident decreased significantly from 20.7 to 3% (p < 0.001) and from 19.2 to 2.9% (p < 0.001), respectively. Simultaneously, an improvement in correct identification of the prescribing physician was registered (from 1.3 to 78.2%). The rest of items analysed were similar in both periods.

Conclusion: The implementation of a structured preventive educational intervention for health professionals in a regional NICU reduced the medication error rate, possibly by the dissemination of a patient safety culture.