bluuebunny/crossref_metadata_2025 huggingface dataset:
Patients’ experiences of living with irritable bowel syndrome
Authors: Rønnevig Marit , Vandvik Per Olav , Bergbom Ingegerd
Published: June 2009

Title.  Patients’ experiences of living with irritable bowel syndrome.

Aim.  This paper is a report of a study conducted to describe people’s experiences, and meanings of these, while living with irritable bowel syndrome.

Background.  Irritable bowel syndrome is characterized by abdominal pain, diarrhoea and/or constipation, distension and bloating. Such symptoms are stigmatized in western societies. Patients may experience negative attitudes from healthcare personnel, and they can feel helpless and frustrated trying to control symptoms.

Method.  A qualitative, hermeneutic approach was used. Open‐ended interviews were conducted during 2005–2006 with 13 patients currently diagnosed with irritable bowel syndrome. The interview setting was a rural healthcare centre or the person’s home. An interpretive analysis of the data was performed.

Findings.  Four interwoven themes were identified in the data: Living with unpredictability, represented by the subthemes ‘not being in control’, ‘not being able to trust’ and ‘invasion of privacy’; preserving dignity, described by ‘living with sacrifice’, ‘taking command’ and ‘fulfilling obligations’; ‘reconciling struggle’; and ‘living with comorbidity’.

Conclusion.  The unpredictability and taboos of irritable bowel syndrome made these people suffer, feel constrained and dependent. Dignity was preserved both by sacrifices and taking command. Healthcare personnel should allow patients to talk about their suffering and discomfort to decrease their experience of suffering. Our study contributes to a more nuanced understanding of life with this unpleasant companion, the suffering it creates and the threats to dignity and health.
Health‐promoting behavior and quality of life among caregivers and non‐caregivers in Taiwan: a comparative study
Authors: Lo Mei Han
Published: June 2009

Title.  Health‐promoting behavior and quality of life among caregivers and noncaregiversin Taiwan: a comparative study.

Aim.  This paper is a report of a study conducted to compare middle‐aged female family caregivers and non‐caregivers in terms of: (a) differences in quality of life and health‐promoting lifestyle behaviors; and (b) the relationship between health‐promoting lifestyle behaviors and quality of life.

Background.  Caregiving for older relatives is a stressful responsibility that detracts from the quality of life of female caregivers and imposes barriers to practising healthy behaviors. Recent studies on caregiving responsibilities have been primarily conducted in Western cultural contexts, with few studies of Chinese groups.

Method.  This cross‐sectional, comparative study included a convenience sample of 39 female caregivers and 98 non‐caregivers recruited in southern Taiwan in 2007. Data were collected using the World Health Organization Quality of Life Instrument‐BREF Taiwanese version and Health Promotion Lifestyle Profile II.

Results.  The majority of caregivers reported a low level of caregiving input with family support. They also reported a statistically significantly higher proportion of health‐promoting behaviors than non‐caregivers, although quality of life did not differ between the two groups. Practising healthy behaviors may more strongly influence quality of life in caregivers than in non‐caregivers.

Conclusion.  Policymakers should consider direct family support and uphold the value of family cohesion in order to maintain healthy behaviors and a high quality of life in family caregivers. Further studies with larger and more comparably‐sized participant groups are recommended to investigate the interactions between levels of care, family support, caregiving consequences, health‐promoting behaviors and the caregivers’ quality of life.
Type 1 diabetes: children and adolescents’ knowledge and questions
Authors: Roper Susanne Olsen , Call Amanda , Leishman Joan , Cole Ratcliffe G. , Mandleco Barbara L. , Dyches Tina T. , Marshall Elaine S.
Published: June 2009

Title.  Type 1 diabetes: children and adolescents’ knowledge and questions.

Aim.  This paper is a report of a study conducted to describe what children and adolescents who have type 1 diabetes know and want to know about the disease.

Background.  Research indicates that young people’s knowledge of diabetes may minimize their health complications, because with greater knowledge they may engage in more effective management practices and adherence.

Methods.  In this qualitative study, a purposive sample of 58 children and adolescents with type 1 diabetes were interviewed in 2005 about what they knew and wanted to know about their disease. Through a process of induction, major themes were identified from the data.

Findings.  The six major themes were: (a) Care, including both physical and emotional care, (b) Physiology, (c) Consequences, including both short‐ and long‐term, as well as positive and negative consequences, (d) Cure, (e) Effects on the Family and (f) Experience at Diagnosis. Themes related to the unique challenges associated with type 1 diabetes were also identified.

Conclusion.  Nurses, diabetes educators and parents should provide developmentally appropriate information about diabetes care and management, scaffolding on existing knowledge. They should provide child‐centred contexts in which children and adolescents can freely ask questions about their condition and problem‐solve. Programmes that allow young people to develop coping skills and share experiences could also prove beneficial.
Migrant nurses’ perceptions and attitudes of integration into the perioperative setting
Authors: Cummins Theresa
Published: June 2009

Title.  Migrant nurses’ perceptions and attitudes of integration into the perioperative setting.

Aim.  This paper is a report of a study conducted to examine migrant nurses’ perceptions and attitudes of integration into the perioperative setting.

Background.  Adapting to a new culture can be overwhelming for many nurses working in foreign countries. Currently, the Republic of Ireland appears to rely heavily on migrant nurses because of persistent nursing shortages over the last decade. To date, there is little research on how the integration process affects migrant nurses in Ireland.

Method.  A quantitative descriptive design was used. Data were collected in 2007 using questionnaires distributed to 220 migrant perioperative nurses working in four hospitals in Ireland.

Results.  There were communication issues between migrant nurses and their work colleagues. Forty‐nine percent of migrant nurses found that work practices were different from those in their home countries. Cultural differences were also an issue. Ninety percent of respondents found the support of preceptors beneficial and 96% found hospital orientation programmes valuable.

Conclusion.  Workshops and in‐service education are needed on key practices and procedures performed in the perioperative setting for all new staff. Specific learning outcomes and an achievement timeframe should be developed for each new nurse, based on their previous experience and level of knowledge. Migrant nurses not accustomed to delegating and being assertive need to be supported and given time to acquire these skills and to gain confidence.
Non‐psychiatric hospitalization of people with mental illness: systematic review
Authors: Zolnierek Cindy Diamond
Published: June 2009

Title.  Non‐psychiatric hospitalization of people with mental illness: systematicreview.

Aim.  This paper is a report of a literature review of the evidence regarding outcomes experienced by severely mentally ill individuals hospitalized in general medical‐surgical settings for non‐psychiatric conditions.

Background.  Severely mentally ill individuals experience chronic medical illnesses at a rate greater than the general population. When hospitalized in non‐psychiatric settings, they tend to be experienced as ‘difficult’ by nurses and to have longer lengths of stay.

Data sources.  The CINAHL and PUBMED databases were searched from 1 to 9 March 2008 to identify studies published between 1998 and 2008 investigating outcomes among people with mental illness hospitalized for non‐psychiatric illness in general hospitals.

Methods.  Included studies were those published in English in peer reviewed journals and investigating patient outcomes. The studies were reviewed for relevance and inclusion criteria; the methodological quality of studies was not evaluated.

Results.  Twelve studies met inclusion criteria. All studies examining length of stay, costs of care or resource utilization showed increased measures for patients with psychiatric comorbidity. Interventions described included psychiatric liaison psychiatry and nursing, which failed to demonstrate improvement in outcomes.

Conclusion.  Nurses play a pivotal role in improving the inpatient care of this vulnerable population, but they struggle in their attempts to do so. Research to determine the best approaches to promote nurses’ knowledge, positive attitudes and self‐confidence in caring for patients with psychiatric comorbidity is needed. Investigation of the patient perspective on the inpatient experience might also provide insight for designing effective care processes.
Promoting an egalitarian approach to research with vulnerable populations of women
Authors: Mkandawire‐Valhmu Lucy , Rice Elizabeth , Bathum Mary Elizabeth
Published: June 2009

Title.  Promoting an egalitarian approach to research with vulnerable populations of women

Aim.  This paper is a presentation of issues that arise when conducting research with women from vulnerable populations.

Background.  Conducting research with ethnic minority populations has accentuated the challenges inherent in research, particularly when the populations participating are considered ‘vulnerable’ due to additional variables such as low levels of income.

Data sources.  The paper is based on the experiences of three authors using feminist methods in separate but similar research trajectories that include (a) low‐income women in the Southern African country of Malawi, (b) women diagnosed with schizophrenia in the United States of America, and (c) rural, indigenous Aymara women of the highlands of Peru. The data forming the basis of this paper were collected over 3‐ to 6‐month periods between 2005 and 2006.

Discussion.  We examine the impact of the researcher’s power on the research process. Our research provides examples that illuminate the limitations of informed consent in research with vulnerable populations of women. We offer critical questions about and recommendations for nursing and other health care researchers, both in the third world and the western world, regarding appropriate research methods with vulnerable populations: methods that acknowledge the oppressive realities of the participants, methods that deliberately avoid further marginalization of participants, and methods that have the potential to improve the life situations of the women who participate in our research.

Conclusion.  These examples show the need for new methods to ensure that participants in research understand their role and the benefits they may expect to receive from research.
Fatigue in children with long‐term conditions: an evolutionary concept analysis
Authors: McCabe Margaret
Published: June 2009

Title.  Fatigue in children with long‐term conditions: an evolutionary concept analysis.

Aim.  This paper is a report of a concept analysis of fatigue in children with long‐term conditions.

Background.  There is little research focused on the experience of fatigue in children. Previous work has focused primarily on children living with cancer. It is necessary to clarify and refine the concept, and add to the knowledge base that supports ongoing theoretical work in order to improve the clinical care of children with long‐term conditions who experience fatigue.

Method.  English language literature published from 1989 to 2007 was searched using the CINAHL, Medline and PsychINFO data bases. Sixty‐two papers and two book chapters were used in this concept analysis. Rodgers’ method of evolutionary concept analysis was used. This inductive method helps us to view the concept in a sociocultural and temporal context.

Findings.  The number of publications focusing on fatigue in children is increasing. The analysis yielded two surrogate terms, five attributes, three antecedents and seven consequences. Based on this analysis, fatigue in children with long‐term conditions appears to be a subjective experience of tiredness or exhaustion that is multidimensional and includes physical, mental, and emotional aspects.

Conclusions.  Evidence suggesting children with long‐term conditions experience fatigue is increasing, but conceptual gaps remain. This analysis has yielded a view of fatigue in children that illustrates healthcare professionals’ limited yet growing awareness of the symptom. Ongoing study as a means to refine our understanding of the concept could potentially lead to important contributions to clinical care of children with long‐term conditions.
Objective structured clinical evaluation of clinical competence: an integrative review
Authors: Walsh Mireille , Bailey Patricia Hill , Koren Irene
Published: June 2009

Title.  Objective structured clinical evaluation of clinical competence: an integrativereview.

Aim.  This paper presents an integrative literature review conducted to describe the utility of the objective structured clinical evaluation (OSCE) as a strategy of measuring one form of clinical competence in nursing.

Background.  The emergence of the OSCE, one form of evaluation of clinical competence used in medicine, is gaining more scrutiny and consideration in nursing education.

Data sources.  The review was conducted through an initial search of computerized databases CINAHL, Cochrane Database of Systematic Reviews, Academic Search Premier and MEDLINE for the period from 1960 to 2008.

Methods.  An integrative review was performed and 41 papers met the inclusion criteria.

Results.  The complexities of evaluating clinical competence can be addressed through use of an OSCE process. Concerns related to the conceptual limitations and the lack of psychometric properties of the tools available for measurement in nursing education have been identified.

Conclusion.  Major gaps exist in the nursing literature regarding the examination of the psychometric properties of the OSCE, the suitability of the design of the OSCE structure and tools for nursing to measure clinical competency, and the associated costs in the application of this evaluative method. Research conducted on the psychometric properties of the OSCE tool used and correlations to other evaluative methods currently used to evaluate nursing clinical competence would inform educational practices.
Population dynamics in a cyclic environment: consequences of cyclic food abundance on tawny owl reproduction and survival
Authors: Karell Patrik , Ahola Kari , Karstinen Teuvo , Zolei Aniko , Brommer Jon E.
Published: June 2009

1.Understanding which factors regulate population dynamics may help us to understand how a population would respond to environmental change, and why some populations are declining.

2.In southern Finland, vole abundance shows a three‐phased cycle of low, increase and decrease phases, but these have been fading out in recent years. During five such cycles (1981–1995), all tawny owlsStrix alucowere censused in a 250‐km2study area, and their reproduction and survival were monitored.

3.Males and females showed similar dynamics, but experienced breeders recruited more offspring and had higher survival than first breeders. Offspring recruitment, but not survival of breeding individuals varied in accordance with vole abundance.

4.The population’s numerical response to prey abundance was primarily due to first‐breeding individuals entering the population in the increase phase when immigration was the highest. First‐breeding birds were younger, but experienced breeders were older in more favourable vole years.

5.A stage‐specific matrix population model integrating survival and fecundity showed that, despite obvious variation in fecundity between vole cycle phases, this variation had limited importance for overall tawny owl population dynamics, but that the survival of experienced breeders during the low phase is most important for population growth.

6.Model and data agreed that the vole cycle drives the dynamics of this avian predator by limiting the recruitment of new breeders during the low phase. Population dynamics hence differ not only from the classic example of the species in a more temperate region in the UK where the number of territories is stable across years, but also from the dynamics of other avian vole predators in Fennoscandia where the recurring crash in vole abundance drastically lowers adult survival thereby creating vacancies.
Size‐dependent predation risk in tree‐feeding insects with different colouration strategies: a field experiment
Authors: Remmel Triinu , Tammaru Toomas
Published: June 2009

1. Body size is positively correlated with fecundity in various animals, but the factors that counterbalance the resulting selection pressure towards large size are difficult to establish. Positively size‐dependent predation risk has been proposed as a selective factor potentially capable of balancing the fecundity advantage of large size.

2. To construct optimality models of insect body size, realistic estimates of size‐dependent predation rates are necessary. Moreover, prey traits such as colouration should be considered, as they may substantially alter the relationship between body size and mortality risk.

3. To quantify mortality patterns, we conducted field experiments in which we exposed cryptic and conspicuous artificial larvae of different sizes to bird predators, and recorded the incidence of bird attacks.

4. The average daily mortality rate was estimated to vary between 4% and 10%. In both cryptic and conspicuous larvae, predation risk increased with prey size, but the increase tended to be steeper in the conspicuous group. No main effect of colour type was found. All the quantitative relationships were reasonably consistent across replicates.

5. Our results suggest that the size dependence of mortality risk in insect prey is primarily determined by the probability of being detected by a predator rather than by a size‐dependent warning effect associated with conspicuous colouration. Our results therefore imply that warningly coloured insects do not necessarily benefit more than the cryptic species from large body size, as has been previously suggested.
Introduced plague lessens the effects of an herbivorous rodent on grassland vegetation
Authors: Hartley Laurel M. , Detling James K. , Savage Lisa T.
Published: June 2009

1. Plague, introduced from Eurasia around 1900, today affects many animal species in the western part of North America, including black‐tailed prairie dogs Cynomys ludovicianus, widespread colonial herbivores of the Central Plains. Most studies of introduced diseases describe how they affect susceptible individuals or populations. We examined the indirect community and ecosystem‐level effects of plague to address the hypothesis that frequent plague epizootics have a mediating effect on the important role of prairie dogs in shaping grassland plant communities.

2. We used 25 years of spatially explicit monitoring data on the Pawnee National Grassland (Colorado, USA) to estimate frequency of plague epizootics in prairie dog colonies. We also examined plant community characteristics of young (3–8 years), old (∼20 years) and plague‐extirpated (7–12 years when extirpated) colonies intermittently to determine how colony age and status (active or inactive) influence the effects of prairie dogs on plant communities.

3. Approximately 98% of colonies experienced a plague epizootic within 15 years of continuous activity, nearly half remained inactive for at least 5 years following an epizootic, and less than half attained their pre‐plague area within 10 years of an epizootic.

4. Prairie dogs lowered plant canopy height, reduced plant biomass and altered plant community composition. These effects were most pronounced for older colonies. Plague‐extirpated colonies were not significantly different from their associated off‐colony sites for most variables measured.

5. 
Synthesis and applications. Our work shows that introduced diseases can indirectly affect community‐ and ecosystem‐level processes through their modification of host species dynamics. Frequent epizootics that lessen the effects of prairie dogs on vegetation probably affect colony‐associated species and grassland food webs. Over 100 animal species are associated with prairie dog colonies because prairie dogs are an important food source and their colonies provide habitat. Prairie dogs are considered competitors with livestock for forage and are exterminated on private lands at considerable expense to ranchers. Extermination may be unwarranted and cost‐ineffective where plague exists because of the high frequency of plague epizootics.
Contribution of ploidy‐level variation and adaptive trait diversity to the environmental distribution of taxa in the ‘fine‐leaved fescue’ lineage (genus Festuca subg. Festuca)
Authors: Sampoux Jean‐Paul , Huyghe Christian
Published: June 2009

Aim  We assessed the relative contribution of ploidy‐level variation and adaptive trait diversity to the diversity of taxon realized niches in a plant lineage with several ploidy levels.

Location  A large number of sites covering a wide range of environmental conditions in France.

Methods  Our material comprised a collection of populations from several taxa of the ‘fine‐leaved fescue’ lineage, namely section Aulaxyper (Festuca rubra s.l.) and subsection Festuca (Festuca ovina s.l.) of the subgenus Festuca. This collection was assessed for several traits related to vegetative growth, investment in seed production, morphology and phenology. Environmental parameters that best differentiate taxon‐realized niches were identified by multivariate ordination and logistic regression. Canonical correlation analyses were performed to relate plant traits and ploidy‐level variation to these environmental parameters. Taxon differentiation was assessed along the first canonical directions of the plant descriptor (plant‐trait and ploidy‐level) space.

Results  The climatic summer water balance, soil texture and land use were identified as the main environmental parameters differentiating taxon realized niches. Canonical correlation analyses revealed associations between plant traits and these environmental parameters, independent of ploidy‐level variation. More specifically, the production of long and abundant rhizomes appeared to be an efficient adaptation to poor climatic summer water balance. In contrast, the ploidy level was rather weakly associated with environmental parameters. The marked prevalence of high ploidy levels in the collection suggests that they could have a competitive advantage in the range of environmental conditions investigated.

Main conclusions  Adaptive trait diversity appears to contribute more than ploidy‐level variation to the present diversity of realized niches for fine‐leaved fescue taxa, although plant‐trait variations were associated to some extent with ploidy‐level variation. However, cytotypes with high ploidy levels could have been efficient colonizers and competitors, favouring the expansion of the lineage and leading to their present prevalence. Furthermore, adaptive trait diversification may have been an efficient factor in niche diversification for the present cytotypes with high ploidy levels.
New distribution limits of seagrass beds in West Africa
Authors: Cunha Alexandra H. , Araújo António
Published: June 2009

The southern limit of the distribution of seagrass species along the west coast of Africa is not yet clearly defined. In March 2008 an expedition was organized in Senegal to search for seagrass beds from Dakar (14°45′15″ N, 17°30′31″ W) southwards to Tabakouta–Delta du Saloum (13°46′59″ N, 16°28′42″ W). Cymodocea nodosa and Halodule wrightii were observed in sandy areas of some protected bays of Dakar, around Sarène (14°16′18″ N, 16°54′17″ W), Joal Fadiouth (14°09′08″ N, 16°50′03″ W) and the Bamboung–Sourou area (13°50′08″ N, 16°33′09″ W), and they probably occur all along the coast of Senegal and beyond, perhaps much further south as well.
Two configurations for accessing classroom computers: differential impact on students' critical reflections and their empowerment
Authors: Solhaug T.
Published: June 2009

The context of this article is the new technological environment and the struggle to use meaningful teaching practices in Norwegian schools. Students' critical reflections in two different technological learning environments in six upper secondary schools are compared. Three of these schools offer Internet‐connected computers in special computer rooms outside ordinary classrooms, while the three other schools offer laptops to every student in class with a wireless connection to the Internet. The study relies on a quasi‐experimental design. Data come from 719 student responses to a survey questionnaire and are analysed using multivariate regression. The findings are that critical reflection is enhanced in classrooms with laptops, controlling for students' motivation, self‐efficacy, gender, grades and cultural background. On this basis, computers could have a significant potential for enhancing reflection and nourishing classroom discourse, knowledge development, and student empowerment. Motivation and self‐efficacy have the strongest impact, while cultural capital has a minor effect on critical thinking. Students' grades seem to have no predictive power with respect to critical reflection. The results are discussed in relation to theories of Bildung, empowerment and democracy. Various implications for teaching are discussed.
Fracture resistance of all‐ceramic crowns placed on a preparation with a slice‐formed finishing line
Authors: ÅKESSON J. , SUNDH A. , SJÖGREN G.
Published: June 2009

Summary  The purpose of this study was to determine the fracture resistance of all‐ceramic crowns with a core of a zirconia ceramic, using various stabilizing oxides and luted on a preparation with a slice‐formed finishing line. Ten cores made of HIPed yttrium‐oxide partially stabilized zirconia (HIPed Y‐TZP) and five cores of densely‐sintered magnesia partially stabilized zirconia (Mg‐PSZ) were made. The Mg‐PSZ cores and five of the HIPed Y‐TZP cores were made with a thickness of 0·2 mm. A further five cores 0·1‐mm thick were made of HIPed Y‐TZP. All 15 cores were then veneered with a feldspar ceramic and luted onto a stylized steel master die model with a slice‐formed finishing line. The specimens were then loaded until fracture occurred. The HIPed Y‐TZP specimens with the 0·2 mm core exhibited significantly higher fracture resistance than the Mg‐PSZ specimens (P = 0·004) and the HIPed Y‐TZP specimens with the 0·1 mm core (P = 0·001). The fracture resistance of the Mg‐PSZ specimens was significantly (P = 0·015) higher than that of the HIPed Y‐TZP specimens with the 0·1 mm core. The fracture resistance determined was equal or superior to reported values for bite forces and all‐ceramic crowns. Thus, it seems likely that the type of restorations evaluated have the potential for successful use on a slice‐formed preparation. However, long‐term studies are essential in order to assess the performance of this ceramic system in a clinical context.
Population genetics of Manihot esculenta ssp. flabellifolia gives insight into past distribution of xeric vegetation in a postulated forest refugium area in northern Amazonia
Authors: DUPUTIÉ ANNE , DELÊTRE MARC , DE GRANVILLE JEAN‐JACQUES , MCKEY DOYLE
Published: June 2009

The Guianas have often been proposed as a forest refugium; however, this view has received little testing. Studies of population genetics of forest taxa suggest that the central part of French Guiana remained forested, while the southern part (currently forested) may have harboured more open vegetation. Insights into the population structure of species restricted to non‐forested habitats can help test this hypothesis. Using six microsatellite loci, we investigated the population genetics of French Guianan accessions of Manihot esculenta ssp. flabellifolia, a taxon restricted to coastal savannas and to rocky outcrops in the densely forested inland. Coastal populations were highly differentiated from one another, and our data suggest a recent colonization of these savannas by M. esculenta ssp. flabellifolia in a west‐to‐east process. Coastal populations were strongly differentiated from inselberg populations, consistent with an ancient separation of these two groups, with no or low subsequent gene flow. This supports the hypothesis that the central part of the region may have remained forested since the Last Glacial Maximum, impeding the establishment of Manihot. Contrary to coastal populations, inselberg Manihot populations were strikingly homogeneous at a broad spatial scale. This suggests they were connected until recently, either by a large continuous savanna area or by smaller, temporary disturbed areas shifting in space.
Upward mobility and alternative lifestyles: a report from the 10th biennial meeting on Bacterial Locomotion and Signal Transduction
Authors: Scharf Birgit E. , Aldridge Phillip D. , Kirby John R. , Crane Brian R.
Published: June 2009

This past January, in Cuernavaca Mexico, a conglomerate of scientists met to discuss the contemporary view of Bacterial Locomotion and Signal Transduction (BLAST). The BLAST meetings represent a field that has its roots in chemotaxis and the flagellum‐based motility but now encompass all types of cellular movement and signalling. The topics varied from the interactions between molecules to the interactions between species. We heard about 3D reconstructions of transmembrane chemoreceptors within cells, new biophysical methods for understanding cellular engines, intricate phosphorelays, elaborate gene networks, new messenger molecules and emerging behaviours within complex populations of cells. At BLAST X we gained an appreciation for the lifestyle choices bacteria make, how they get to where they are going and the molecular mechanisms that underlie their decisions. Herein we review the highlights of the meeting.
The yeast Shu complex couples error‐free post‐replication repair to homologous recombination
Authors: Ball Lindsay G. , Zhang Ke , Cobb Jennifer A. , Boone Charles , Xiao Wei
Published: June 2009

DNA post‐replication repair (PRR) functions to bypass replication‐blocking lesions and prevent damage‐induced cell death. PRR employs two different mechanisms to bypass damaged DNA. While translesion synthesis has been well characterized, little is known about the molecular events involved in error‐free bypass, although it has been assumed that homologous recombination (HR) is required for such a mode of lesion bypass. We undertook a genome‐wide synthetic genetic array screen for novel genes involved in error‐free PRR and observed evidence of genetic interactions between error‐free PRR and HR. Furthermore, this screen identified and assigned four genes, CSM2, PSY3, SHU1 and SHU2, whose products form a stable Shu complex, to the error‐free PRR pathway. Previous studies have indicated that the Shu complex is required for efficient HR and that inactivation of any of these genes is able to suppress the severe phenotypes of top3 and sgs1. We confirmed and further extended some of the reported observations and demonstrated that error‐free PRR mutations are also epistatic to sgs1. Based on the above analyses, we propose a model in which error‐free PRR utilizes the Shu complex to recruit HR to facilitate template switching, followed by double‐Holliday junction resolution by Sgs1‐Top3. This mechanism appears to be conserved throughout eukaryotes.
Novel role of Wag31 in protection of mycobacteria under oxidative stress
Authors: Mukherjee Partha , Sureka Kamakshi , Datta Pratik , Hossain Tofajjen , Barik Subhasis , Das Kali P. , Kundu Manikuntala , Basu Joyoti
Published: June 2009

Wag31 of Mycobacterium tuberculosis belongs to the DivIVA family of proteins known to regulate cell morphology in Gram‐positive bacteria. Here we demonstrate an unrecognized, novel role of Wag31 in oxidatively stressed mycobacteria. We report the cleavage of penicillin‐binding protein 3 (PBP3) by the intramembrane metalloprotease Rv2869c (MSMEG_2579) in oxidatively stressed cells. Amino acids 102A and 103A of PBP3 are required for Rv2869c‐mediated cleavage. Wag31MTB, by virtue of its interaction with PBP3 through amino acid residues 46NSD48, protects it from oxidative stress‐induced cleavage. PBP3 undergoes cleavage in Mycobacterium smegmatis (strain PM2) harbouring wag31(Δ46NSD48) instead of the wild type, with concomitant reduction in ability to withstand oxidative stress. Overexpression of Wag31(Δ46NSD48) attenuates the survival of M. tuberculosis in macrophages with concomitant cleavage of PBP3, and renders the organism more susceptible towards hydrogen peroxide as well as drugs which generate reactive oxygen species, namely isoniazid and ofloxacin. We propose that targeting Wag31 could enhance the activity of mycobactericidal drugs which are known to generate reactive oxygen species.
Effects of postgastric 13C‐acetate processing on measurement of gastric emptying: a systematic investigation in health
Authors: Goetze O. , Fox M. , Kwiatek M. A. , Treier R. , Schwizer W. , Thumshirn M. , Fried M. , Fruehauf H.
Published: June 2009

Abstract  Uniform postgastric processing of the gastric emptying (GE) marker 13C‐acetate (Ac) is an unverified assumption behind its widespread application to measure GE. This study assessed the postgastric processing of Ac administered by intraduodenal (i.d.) infusion simulating different physiological conditions. 13CO2 in breath was assessed in three groups of six volunteers after i.d. administration of A: Different caloric densities (0.75/1.5/3 kcal min−1) in a 200 mL meal at constant 1 mg Ac min−1 simulating a physiological range of nutrient delivery rates; B: different tracer delivery rates (0.5/1.0/2.5 mg Ac min−1) simulating delayed, normal and increased GE; C1: a 500 mL meal resulting in same marker and caloric delivery compared to protocol A; C2: 50 mL water bolus injections of 12.5/25/50/100 mg Ac and C3 bolus injections of 50 mg Ac in 50/100/200 mL water in randomized order. A: 13CO2 excretion was independent of caloric load (P = 0.59). B: The dynamic of 13CO2 excretion was modulated by tracer elimination which was in turn dependent on the speed of tracer delivery, i.e. with faster deliveries resulting in lower 13CO2 recovery during infusion (P < 0.001). C: Increasing Ac doses resulted in decreased 13CO2 recovery (P < 0.001) over the first hour. 13CO2 recovery kinetics was independent of the volume delivered. This study shows 13C‐acetate absorption and metabolism is independent of the volume and caloric delivery of test meals. The ‘lag’ in estimates of GE derived from 13CO2 breath tests is due to a postgastric, dose‐dependent delay to 13CO2 elimination. This can be corrected for in analytical derivations of GE parameters based on 13C‐acetate breath test measurements.
PRECLINICAL STUDY: Route of administration affects the ability of naltrexone to reduce amphetamine‐potentiated brain stimulation reward in rats
Authors: Todtenkopf Mark S. , O'Neill Krystal S. , Kriksciukaite Kristina , Turncliff Ryan Z. , Dean Reginald L. , Ostrovsky‐Day Irina , Deaver Daniel R.
Published: June 2009

Opioid receptor antagonism has been shown to attenuate behavioral and neurochemical effects of amphetamine in humans and rodents. The effects of acute (oral or subcutaneous) or extended‐release naltrexone (XR‐NTX) were tested on the reward‐enhancing effects of amphetamine using the intracranial self‐stimulation (ICSS) paradigm. Acute exposure to drugs of abuse reduces the locus of rise (LOR) in the ICSS procedure, reflecting enhanced brain stimulation reward (BSR). Rats were treated once a day with naltrexone orally (PO; 5.0 mg/kg) or subcutaneously (SC; 0.5 mg/kg) for four consecutive days and tested with D‐amphetamine (0.5 mg/kg, intraperitoneal) in the ICSS paradigm 30 minutes later on days 1 and 4. Separate groups of rats received XR‐NTX (50 mg/kg, SC) or placebo microspheres (similar mass to XR‐NTX, SC) on day 0 and tested with D‐amphetamine in the ICSS paradigm on days 4, 14, 21, 28 and 41 after administration. Naltrexone plasma concentrations were determined for each amphetamine testing session using liquid chromatography‐mass spectrometry/mass spectrometry (LC‐MS/MS). In rats pretreated with naltrexone acutely, amphetamine‐potentiated BSR did not differ from vehicle‐pretreated rats on either day 1 or day 4 (25–30% decrease in LOR). In XR‐NTX‐pretreated rats, amphetamine‐potentiated BSR was reduced by 64 and 70% on days 4 and 14, respectively, compared to placebo microsphere‐treated controls. This effect dissipated by day 21. Naltrexone plasma concentrations were comparable across all treatment groups (14–30 ng/ml) on days 1, 4 and 14. In summary, an extended‐release formulation of naltrexone results in significant attenuation of psychostimulant‐enhanced BSR that is not observed with acute naltrexone.
PRECLINICAL STUDY: Electroacupuncture treatment reverses morphine‐induced physiological changes in dopaminergic neurons within the ventral tegmental area
Authors: Hu Ling , Chu Ning‐ning , Sun Lin‐lin , Zhang Rong , Han Ji‐Sheng , Cui Cai‐lian
Published: June 2009

Chronic morphine administration decreases the size of dopamine (DA) neurons in the ventral tegmental area (VTA). These transient morphological changes are accompanied by a reduced sensitivity of morphine‐induced conditioned place preference (CPP) after chronic exposure to the drug. In this study we examined alterations in the firing rate of DAergic neurons by means of extracellular recording following chronic morphine exposure and applied 100 Hz electroacupuncture (EA) treatment to reverse the reduced firing rate of these neurons. In the first set of experiments we show that in rats, which received chronic morphine treatment for 14 days, a small dose of morphine was not able to induce a CPP response anymore. However, the sensitivity to morphine was reinstated by consecutive EA treatment for 10 days. The electrophysiological response of VTA DA neurons to morphine was markedly reduced in chronic morphine‐treated rats compared to saline‐treated controls. A substantial recovery of the reactivity of VTA DA neurons to morphine was observed in rats that received 100 Hz EA for 10 days. Our findings suggest that 100 Hz EA is a potential therapy for the treatment of opiate addiction by normalizing the activity of VTA DA neurons.
PRECLINICAL STUDY: Is withdrawal hyperalgesia in morphine‐dependent mice a direct effect of a low concentration of the residual drug?
Authors: Rubovitch Vardit , Pick Chaim G , Sarne Yosef
Published: June 2009

Withdrawal of opioid drugs leads to a cluster of unpleasant symptoms in dependent subjects. These symptoms are stimulatory in nature and oppose the acute, inhibitory effects of opiates. The conventional theory that explains the opioid withdrawal syndrome assumes that chronic usage of opioid drugs activates compensatory mechanisms whose stimulatory effects are revealed upon elimination of the inhibitory opioid drug from the body. Based on previous studies that show a dose‐dependent dual activity of opiates, including pain perception, we present here an alternative explanation to the phenomenon of withdrawal‐induced hyperalgesia. According to this explanation, the residual low concentration of the drug that remains after cessation of its administration elicits the stimulatory withdrawal hyperalgesia. The goal of the present study was to test this hypothesis. In the present study we rendered mice dependent on morphine by a daily administration of the drug. Cessation of morphine application elicited withdrawal hyperalgesia that was completely blocked by a high dose of the opiate antagonist naloxone (100 mg/kg). Similarly, naloxone (2 mg/kg)‐induced withdrawal hyperalgesia was also blocked by 100 mg/kg of naloxone. The blockage of withdrawal hyperalgesia by naloxone suggested the involvement of opioid receptors in the phenomenon and indicated that withdrawal hyperalgesia is a direct effect of a residual, low concentration of morphine. Acute experiments that show morphine‐ and naloxone‐induced hyperalgesia further verified our hypothesis. Our findings offer a novel, alternative approach to opiate detoxifications that may prevent withdrawal symptoms by a complete blockage of the opioid receptors using a high dose of the opioid antagonist.
Targeting the allergen to oral dendritic cells with mucoadhesive chitosan particles enhances tolerance induction
Authors: Saint‐Lu N. , Tourdot S. , Razafindratsita A. , Mascarell L. , Berjont N. , Chabre H. , Louise A. , Van Overtvelt L. , Moingeon P.
Published: June 2009

Background:  Sublingual immunotherapy (SLIT) efficacy could be improved by formulations facilitating allergen contact with the oral mucosa and uptake by antigen‐presenting cells (APCs).

Methods:  Two types of chitosan microparticles, differing in size and surface charge, were tested in vitro for their capacity to improve antigen uptake and presentation by murine bone marrow‐derived dendritic cells (BMDCs) or purified oral APCs. T‐cell priming in cervical lymph nodes (LNs) was assessed by intravenous transfer of carboxyfluorescein diacetate succinimidyl ester‐labelled ovalbumin (OVA)‐specific CD4+ T cells and flow cytometry analysis. Ovalbumin‐sensitized BALB/c mice were treated sublingually with soluble or chitosan‐formulated OVA twice a week for 2 months. Airway hyperresponsiveness (AHR), lung inflammation and T‐cell responses in cervical and mediastinal LNs were assessed by whole‐body plethysmography, lung histology and Cytometric Bead Array technology, respectively.

Results:  Only a mucoadhesive (i.e. highly positively charged) and microparticulate form of chitosan enhances OVA uptake, processing and presentation by murine BMDCs and oral APCs. Targeting OVA to dendritic cells with this formulation increases specific T‐cell proliferation and IFN‐γ/IL‐10 secretion in vitro, as well as T‐cell priming in cervical LNs in vivo. Sublingual administration of such chitosan‐formulated OVA particles enhances tolerance induction in mice with established asthma, with a dramatic reduction of both AHR, lung inflammation, eosinophil numbers in bronchoalveolar lavages, as well as antigen‐specific Th2 responses in mediastinal LNs.

Conclusions:  Mucoadhesive chitosan microparticles represent a valid formulation for sublingual allergy vaccines.
CD40 and OX40 ligand are differentially regulated on asthmatic airway smooth muscle
Authors: Krimmer D. I. , Loseli M. , Hughes J. M. , Oliver B. G. G. , Moir L. M. , Hunt N. H. , Black J. L. , Burgess J. K.
Published: June 2009

Background: CD40 and OX40 Ligand (OX40L) are cell‐surface molecules expressed on airway smooth muscle (ASM) that can enhance inflammatory cell activation and survival. The aim of this study was to examine the effect of tumour necrosis factor‐alpha (TNF‐α) and interferon‐gamma (IFN‐γ) on ASM CD40 and OX40L expression.

Methods: CD40 and OX40L expression on human ASM cells from asthmatic and nonasthmatic donors following stimulation with TNF‐α and/or IFN‐γ was measured using cell‐surface enzyme‐linked immunosorbent assay (ELISA) and flow cytometry. Involvement of signalling pathway was investigated with pharmacological inhibitors. Soluble TNF receptor levels were quantified by ELISA.

Results: Interferon‐γ and TNF‐α synergistically increased CD40 expression to a greater extent on asthmatic than on nonasthmatic ASM. In contrast, IFN‐γ reduced TNF‐α‐induced OX40L expression to a similar extent in both cell types. TNF‐α and IFN‐γ induced CD40 via nuclear factor‐κB (NF‐κB) and signal transducer and activator of transcription‐3 in both cell types and modulated OX40L via NF‐κB and c‐Jun N terminal kinase in nonasthmatic cells. Similar effects on the induction of OX40L in asthmatic cells were seen with NF‐κB, but these were not statistically significant. The reduced OX40L expression with TNF‐α and IFN‐γ involved extracellular regulated kinase 1/2 activation.

Conclusion: Asthmatic ASM may modulate airway inflammation locally by increasing CD40 and OX40L expression in response to cytokines. IFN‐γ may regulate ASM pro‐inflammatory actions by differentially modulating ASM CD40 and OX40L expression.
Longitudinal trends of total and allergen‐specific IgE throughout childhood
Authors: Matricardi P. M. , Bockelbrink A. , Grüber C. , Keil T. , Hamelmann E. , Wahn U. , Lau S.
Published: June 2009

Background:  The development and the quantitative relationship between allergen‐specific IgE (S‐IgE) responses and total IgE (T‐IgE), during childhood and adolescence have not been described and understood in detail. The objective of this study was to describe and compare the longitudinal trends of serum levels of S‐IgE and T‐IgE during childhood.

Methods:  We analysed data from participants in the MAS birth cohort study at 2, 5, 7 and 10 years of age (n = 273) and at 1, 3, 5, 6, 7, 10 and 13 years (n = 84). Total‐IgE and the overall level of specific‐IgE against nine locally relevant airborne and food allergens were determined by FEIA (ImmunoCAP). Allergic rhino‐conjunctivitis and asthma were ascertained by questionnaires.

Results:  Longitudinal patterns of T‐IgE levels from age 1 to 13 years were highly heterogeneous (declining, flat or increasing with different profiles). From 5 years of age, logarithmic (log10) transformed values of T‐IgE and of S‐IgE levels tend to follow a parallel trend, so that their relation remained constant throughout school age. A flat trend of T‐IgE vs a constantly increasing trend of T‐IgE was associated with a low or, respectively, high rate of wheezing at 13 years of age.

Conclusions:  Beginning at the age of 5 years, total serum IgE levels in children from an industrialized country evolved in parallel with overall S‐IgE levels. Therefore, variations in T‐IgE levels at school age closely reflect variations in overall S‐IgE levels. Further studies are required to strengthen the biological and clinical implication of this novel finding.
Blockade of CCR4 in a humanized model of asthma reveals a critical role for DC‐derived CCL17 and CCL22 in attracting Th2 cells and inducing airway inflammation
Authors: Perros F. , Hoogsteden H. C. , Coyle A. J. , Lambrecht B. N. , Hammad H.
Published: June 2009

Background:  As Th2 type lymphocytes orchestrate the cardinal features of allergic asthma, inhibiting their recruitment to the lungs could be of therapeutic benefit. Although human Th2 cells express the CCR4 chemokine receptor and increased production of CCR4 ligands has been found in asthmatic airways, studies in animals have reached contradictory conclusions on whether blocking this pathway would be beneficial.

Objective:  As a lack of efficacy might be due to differences between mouse and man, we readdressed this question using a humanized severe combined immunodeficiency model of asthma.

Methods:  Mice received peripheral blood mononuclear cells from house dust mite (HDM) allergic asthmatic patients and then underwent bronchial challenge with HDM.

Results:  This resulted in marked allergic inflammation and bronchial hyper‐reactivity. Administration of CCR4 blocking antibody abolished the airway eosinophilia, goblet cell hyperplasia, IgE synthesis and bronchial hyperreactivity. In this chimeric system, human CD11c+ dendritic cells (DCs) were the predominant source of CCR4 ligands, suggesting that DC‐derived chemokines attract Th2 cells. In separate experiments using human DCs, in vitro exposure to HDM of DCs from HDM allergic patients but not healthy controls caused CCL17 and CCL22 release that resulted in chemoattraction of polarized human Th2 cells in a CCR4‐dependent way.

Conclusions:  Taken together, our data provide proof of concept that CCR4 blockade inhibits the salient features of asthma and justify further clinical development of CCR4 antagonists for this disease.