bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring the Capillary‐Alveolar Leakage in an A.R.D.S. Model Using Broncho‐Alveolar Lavage
Authors: Briot Raphael , Bayat Sam , Anglade Daniel , Martiel Jean‐Louis , Grimbert Francis
Published: April 2008

Objectives: We developed a modified broncho‐alveolar lavage (BAL) technique in order to perform repeated measurements of capillary‐alveolar leakage of a macromolecule in oleic acid (OA)‐induced lung injury.

Methods: BAL was performed in anesthetized dogs in a closed lung sampling site, using a bronchoscope fitted with an inflatable cuff. Fluorescein‐labeled Dextran (FITC‐D70) was continuously infused and its concentration measured in plasma and BAL fluid. A two‐compartment model (blood and alveoli) was used to calculate KAB, the transport‐rate coefficient of FITC‐D70 from blood to alveoli. KAB was estimated every 15 minutes over three hours.

Results: KAB, close to zero at base‐line both in control (n = 3) and in OA‐injured lungs (n = 7), reached a peak in permeability 30 minutes after the induction of OA injury (KAB = 1.43 ± 0.31 · 10−3 · minutes−1), followed by a slow recovery.

Conclusions: We conclude that this technique allows the monitoring of capillary‐alveolar transport of macromolecules in in vivo experimental models. This monitoring may prove useful to study the mechanisms of the exudative stage of acute lung injury and to test therapies aimed at slowing the alveolar accumulation of plasma proteins and procoagulant factors that contribute to alveolar fibrosis.
Reprocessing and Reuse of Single-Use Medical Devices: A National Survey of Canadian Acute-Care Hospitals
Authors: Polisena Julie , Hailey David , Moulton Kristen , Noorani Hussein Z. , Jacobs Philip , Ries Nola , Normandin Sarah , Gardam Michael
Published: April 2008

A national survey investigated the current practices of reprocessing and reusing single-use medical devices in Canadian acute-care hospitals. Our response rate was 72% (413 responses), and 28% of hospitals reprocess single-use devices. The results showed that Canadian hospital practices have not changed much in the past decade.
Effect of Accessibility of Influenza Vaccination on the Rate of Childcare Staff Vaccination
Authors: Lee Ingi , Thompson Sarah , Lautenbach Ebbing , Gasink Leanne B. , Watson Barbara , Fishman Neil O. , Chen Zhen , Linkin Darren R.
Published: April 2008

We assessed the impact of free on-site influenza vaccination on childcare staff vaccination prevalence using 2 before-and-after studies. Vaccination was offered during the 2003-2004 and 2006-2007 influenza seasons. Staff vaccination prevalence was higher in each intervention season compared to the prior, nonintervention season. No baseline characteristics were associated with receipt of vaccination.
Methicillin-Resistant Staphylococcus aureus Infection in a College Football Team: Risk Factors Outside the Locker Room and Playing Field
Authors: Archibald Lennox K. , Shapiro Jerne , Pass Anthony , Rand Kenneth , Southwick Frederick
Published: April 2008

We investigated a cluster of methicillin-resistant Staphylococcus aureus infections in college football players. Risk factors included a history of recurrent skin infections and contact with the skin lesions of persons outside college. The infections were controlled through treatment of carriers with topical mupirocin, chlorhexidine body washes, and enhancement of personal hygiene practices. Varsity and professional teams need to consider similar preventive measures.
Cds1 Controls the Release of Cdc14-like Phosphatase Flp1 from the Nucleolus to Drive Full Activation of the Checkpoint Response to Replication Stress in Fission Yeast
Authors: Díaz-Cuervo Helena , Bueno Avelino
Published: April 2008

The Cdc14p-like phosphatase Flp1p (also known as Clp1p) is regulated by cell cycle-dependent changes in its subcellular localization. Flp1p is restricted to the nucleolus and spindle pole body until prophase, when it is dispersed throughout the nucleus, mitotic spindle, and medial ring. Once released, Flp1p antagonizes Cdc2p/cyclin activity by reverting Cdc2p-phosphorylation sites on Cdc25p. On replication stress, ataxia-telangiectasia mutated/ATM/Rad3-related kinase Rad3p activates Cds1p, which phosphorylates key proteins ensuring the stability of stalled DNA replication forks. Here, we show that replication stress induces changes in the subcellular localization of Flp1p in a checkpoint-dependent manner. Active Cds1p checkpoint kinase is required to release Flp1p into the nucleus. Consistently, a Flp1p mutant (flp1-9A) lacking all potential Cds1p phosphorylation sites fails to relocate in response to replication blocks and, similarly to cells lacking flp1 (Δflp1), presents defects in checkpoint response to replication stress. Δflp1 cells accumulate reduced levels of a less active Cds1p kinase in hydroxyurea (HU), indicating that nuclear Flp1p regulates Cds1p full activation. Consistently, Δflp1 and flp1-9A have an increased percentage of Rad22p-recombination foci during HU treatment. Together, our data show that by releasing Flp1p into the nucleus Cds1p checkpoint kinase modulates its own full activation during replication stress.
RAB-11 Permissively Regulates Spindle Alignment by Modulating Metaphase Microtubule Dynamics inCaenorhabditis elegansEarly Embryos
Authors: Zhang Haining , Squirrell Jayne M. , White John G.
Published: April 2008

Alignment of the mitotic spindle along a preformed axis of polarity is crucial for generating cell diversity in many organisms, yet little is known about the role of the endomembrane system in this process. RAB-11 is a small GTPase enriched in recycling endosomes. When we depleted RAB-11 by RNAi in Caenorhabditis elegans, the spindle of the one-cell embryo failed to align along the axis of polarity in metaphase and underwent violent movements in anaphase. The distance between astral microtubules ends and the anterior cortex was significantly increased in rab-11(RNAi) embryos specifically during metaphase, possibly accounting for the observed spindle alignment defects. Additionally, we found that normal ER morphology requires functional RAB-11, particularly during metaphase. We hypothesize that RAB-11, in conjunction with the ER, acts to regulate cell cycle–specific changes in astral microtubule length to ensure proper spindle alignment in Caenorhabditis elegans early embryos.
Nitric oxide is involved in appetitive but not aversive olfactory learning in the land mollusk Limax valentianus
Authors: Yabumoto Taiki , Takanashi Fumihito , Kirino Yutaka , Watanabe Satoshi
Published: April 2008

The land slug Limax performs both aversive and appetitive olfactory learning, and we investigated neurotransmitters involved in each type of learning. Slugs were conditioned by presenting a vegetable juice (appetitive conditioning) or a mixture of vegetable juice and quinidine (aversive conditioning), and the latency to reach the juice became shorter (appetitive conditioning) or longer (aversive conditioning) after conditioning. L-NAME injected either before conditioning or testing blocked the reduction in latency in appetitive conditioning but had no significant effects in aversive conditioning. 5,7-dihydroxytryptamine had no significant effects in appetitive conditioning. These results suggest different mechanisms for appetitive and aversive learning.
Systemic and bronchodilator effects of inhaled rac‐formoterol in subjects with chronic obstructive pulmonary disease: a dose–response study
Authors: Whale Christopher I. , Sovani Milind P. , Mortimer Kevin J. , Harrison Timothy W. , Tattersfield Anne E.
Published: April 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The long‐acting inhaled β2‐agonist formoterol has systemic effects when taken in high doses.

• It can be used as relief medication in asthma and there is interest in this approach in chronic obstructive pulmonary disease (COPD).

• Relief medication can involve high doses, and in subjects with COPD who have limited ability to bronchodilate the adverse effects can outweigh the benefits.

• There are concerns with the overall safety of high‐dose β2‐agonists in subjects with COPD, and this study looks at the balance of beneficial and adverse effects of a range of doses of inhaled formoterol.

WHAT THIS STUDY ADDS

• Among subjects with COPD, high‐dose inhaled formoterol produced a dose‐related increase in forced expiratory volume in 1 s without a corresponding reduction in dyspnoea or increase in walk distance.

• Systemic effects were modest, however, and high doses did not appear to reduce patient satisfaction.

• Although further safety data are needed, inhaled formoterol may have a role as relief medication in COPD.

AIMS Rac‐formoterol is effective as maintenance treatment for both asthma and chronic obstructive pulmonary disease (COPD) and is now used as relief therapy in asthma. Using rac‐formoterol for relief and maintenance treatment could involve inhalation of high doses, and whether this is of benefit in COPD is uncertain. Our aim was to determine whether higher doses of inhaled rac‐formoterol produce systemic adverse effects that outweigh the limited bronchodilator benefit seen in subjects with COPD.

METHODS We examined airway and systemic effects of 6, 12, 24 and 48 μg rac‐formoterol and placebo on separate days in 20 subjects with symptomatic COPD [forced expiratory volume in 1 s (FEV1) 47% predicted]. FEV1, oxygen saturation, dyspnoea, 6‐min walk distance, patient satisfaction and systemic effects were measured and treatment was assessed against placebo and for dose–response effects.

RESULTS FEV1[area under the time–response curve (AUC)] and satisfaction scores increased with all formoterol doses compared with placebo, as did AUC tremor with the 24‐ and 48‐μg doses and AUC heart rate with the 48‐μg dose. A dose–response relationship was seen with FEV1 and tremor, but not with satisfaction scores. There was no difference between placebo and rac‐formoterol for other variables.

CONCLUSIONS Our results show that in patients with COPD rac‐formoterol improves FEV1 and patient satisfaction without a corresponding reduction in dyspnoea. Since the systemic effects from a relatively high dose were minimal, its use as relief medication in COPD merits further evaluation.
Lipid‐lowering therapy does not affect the postprandial drop in high density lipoprotein‐cholesterol (HDL‐c) plasma levels in obese men with metabolic syndrome: a randomized double blind crossover trial
Authors: Hajer Gideon R. , Dallinga‐Thie Geesje M. , Van Vark‐van der Zee Leonie C. , Olijhoek Jobien K. , Visseren Frank L. J.
Published: April 2008

Introduction  The postprandial lipid metabolism in metabolic syndrome patients is disturbed and may add to the increased cardiovascular risk in these patients. It is not known whether postprandial high density lipoprotein‐cholesterol (HDL‐c) metabolism is also affected and whether this can be influenced by statin and/or ezetimibe treatment.

Methods  Prospective, randomized, double blind, crossover trial comparing simvastatin 80 mg with simvastatin/ezetimibe 10 mg/10 mg treatment for 6 weeks on postprandial HDL‐c metabolism in 15, nonsmoking, male, obese metabolic syndrome patients (Adult Treatment Panel III, ATPIII). Only study medication was allowed. HDL‐c concentrations, cholesteryl ester transfer (CET), CET protein (CETP) mass and adiponectin were measured before and after oral fat loading. ClinicalTrials.gov NCT00189085.

Results  Plasma HDL‐c levels remained stable during continuous fasting following an overnight fast. Pre‐fat load HDL‐c concentrations without treatment, after simvastatin and simvastatin/ezetimibe treatment were 1·15 ± 0·04, 1·16 ± 0·05 and 1·11 ± 0·04 mmol/l. Fat load induced a 11% drop in HDL‐c plasma levels; 1·02 ± 0·05 mmol/l (P < 0·001) which was not affected by either therapy. Triglyceride levels during fat load were similar after both treatments. Total CET increased from 9·73 ± 0·70 to 12·20 ± 0·67 nmol/ml/h (P = 0·004). Four hours after fat loading CETP mass was increased while adiponectin levels were decreased, irrespective of treatment.

Discussion  HDL‐c levels decrease as CET increases after fat loading in obese metabolic syndrome patients. This is not influenced by either simvastatin or simvastatin/ezetimibe treatment. After fat loading, CETP mass and CET increased, and adiponectin decreased pointing towards a potential role for intra‐abdominal fat. Decreased postprandial HDL‐c levels may contribute to the increased cardiovascular risk in metabolic syndrome patients on top of already low HDL‐c levels.
Proliferation and apoptosis of tumour cells before and after neoadjuvant therapy for high‐grade extremity sarcomas: divergent associations with tumour response and prognosis
Authors: Matsubara T , Eimoto T , Okabe M , Miyabe S , Fujiyoshi Y , Matsushita Y , Mizutani J , Yamada S , Otsuka T
Published: April 2008

Aims:  To evaluate proliferation and apoptosis in high‐grade sarcomas of the extremities before and after preoperative radio‐hyperthermo‐chemotherapy (RHC) and to determine the relationship between these parameters and treatment outcomes.

Methods and results:  Pre‐ and post‐RHC specimens of 41 soft tissue and bone tumours were immunohistochemically stained for minichromosome maintenance protein (MCM) 2 and caspase 3 as proliferation and apoptosis markers, respectively, based on a preliminary study comparing them with conventional markers. Indices were calculated as a percentage of positive cells by counting tumour cells in the most frequently labelled areas. MCM2, caspase 3 and MCM2/caspase 3 (growth) indices were 45.3 ± 21.9%, 4.1 ± 7.1% and 82.9 ± 104.5, respectively, in pre‐RHC specimens and 35.4 ± 30.8%, 39.2 ± 34.6% and 5.3 ± 11.7, respectively, in post‐RHC specimens. Response scores showed positive correlation with pre‐RHC MCM2 and post‐RHC caspase 3 indices, inverse correlation with post‐RHC MCM2 and post‐RHC growth indices and no correlation with prognosis. Multivariate analysis revealed high pre‐RHC MCM2 and high post‐RHC growth indices as significant unfavourable prognostic factors.

Conclusions:  High proliferative activity in untreated sarcoma may predict good response to neoadjuvant therapy, but poor prognosis, whereas a high growth index, i.e. high proliferation:apoptosis ratio in a post‐neoadjuvant therapy tumour specimen may indicate poor response and poor prognosis.
Parent–adolescent communication and diabetes: an integrative review
Authors: Dashiff Carol , Hardeman Traci , McLain Rhonda
Published: April 2008

Title.  Parent–adolescent communication and diabetes: an integrative review.

Aim.  This paper presents a synthesis of findings from empirical studies about communication and interaction between parents and their adolescents with diabetes.

Background.  Communication between parent and adolescent is essential in transitioning the adolescent to increased responsibility for diabetes self‐management. Nurses are in a pivotal position to enhance the type of parent–adolescent communication that facilitates this transition.

Data sources.  A search of published studies from 1985 to 2006 featuring communication or interaction between parents and adolescents with type 1 diabetes was implemented through a computerized search.

Review methods.  Papers were organized by type of evidence and were analysed sequentially. Sources were described based on data elements which were extracted. Findings in the areas of productive and problematic parent–adolescent communications were included. Data elements were compared and critiqued, noting consistencies, and findings were summarized and evaluated.

Results.  Studies across several countries indicate that maternal support, conflict, control, involvement and emotional expression are important communication concepts that are linked to diabetes outcomes in adolescents. The influences of different family structures and cultural and socioeconomic circumstances, as well as developmental status and gender of adolescents on these types of communication, have not been systematically studied.

Conclusion.  Nurses caring for adolescents with type 1 diabetes need to consider family relationships and communication patterns in achieving health outcomes. Studies of communication, including perspectives of mothers and fathers, and the influence of family structure, economics and culture are needed to build a framework of parent–adolescent interaction and health outcomes for adolescents with type 1 diabetes.
Development and validation of a brief Occupational Coping Self‐Efficacy Questionnaire for Nurses
Authors: Pisanti Renato , Lombardo Caterina , Lucidi Fabio , Lazzari David , Bertini Mario
Published: April 2008

Title. Development and validation of a brief Occupational Coping Self‐Efficacy Questionnaire for Nurses

Aim. This paper is a report of a study to develop and test the psychometric properties of the Occupational Coping Self‐Efficacy for Nurses Scale.

Background. Coping self‐efficacy beliefs are defined as self‐appraisals of capabilities to cope with environmental demands. People with higher levels of coping self‐efficacy beliefs tend to approach challenging situations in an active and persistent way, whereas those with lower levels of coping self‐efficacy beliefs tend to direct greater energy to managing increasing emotional distress.

Method. In 2006, 1383 nurses completed the following measures: Occupational Coping Self‐Efficacy Questionnaire for Nurses, Coping Inventory for Stressful Situations Short Form and Maslach Burnout Inventory. Based on a randomized split of the data, we conducted exploratory factor analysis on group 1 data (n = 691) and confirmatory factor analysis within the framework of structural equation modelling on group 2 data (n = 692).

Findings. The exploratory results revealed two factors: Coping Self‐Efficacy to cope with the occupational burden (Cronbach alpha = 0·77) and Coping Self‐Efficacy to cope with the relational burden (alpha = 0·79). In the confirmatory group, the two‐factor structure was tested against an alternative one‐factor structure and confirmed as the best solution. Correlation patterns between the Occupational Coping Self‐Efficacy for Nurses Scales, and both coping and burnout variables, supported the criterion‐related validity of the Occupational Coping Self‐Efficacy for Nurses dimensions.

Conclusion. Nurses can have two basic and distinct coping self‐efficacy beliefs: beliefs about occupational burden and beliefs about relational difficulties in the workplace. Research is needed into how efficacy evaluations shift as a result of specific stress management interventions.
All referrals completed? The issues of liaison and documentation when discharging older people from an emergency department to home
Authors: Dunnion Mary E , Kelly Billy
Published: April 2008

Aims.  To examine key aspects of the management of the older person in preparation for discharge home from the emergency department to the primary care sector by examining the present levels and organisation of referrals.

Background.  Older people usually present at emergency departments in response to a medical crisis in their lives. A seamless transition across organisational boundaries is necessary for providing quality health care and to avoid fragmentation of care provision following discharge. Evidence suggests that a lack of communication, documentation and continuity of care between healthcare sectors generally exists.

Design.  The sample comprised the total population (n = 222) of all medical and nursing staff in the emergency department of one regional hospital and primary care area associated with it. A purposeful sample was used as some members of the primary care team were excluded from the sample.

Methods.  The method adopted was a survey approach which employed the use of standardised questionnaires comprising both open and closed questioning styles. Raw statistical data were analysed using spss for Windows while the qualitative data arising from the open‐ended questions were content analysed for themes.

Results.  The findings of this study support previous research in that older people continue to be discharged from the emergency department with inadequately determined aftercare needs and deficits in communications with the primary care sector.

Conclusion.  Current communication between emergency departments and the primary care sector would appear to be disjointed, indicating a need to develop effective referral criteria, accurate documentation and prompt referral.

Relevance to clinical practice.  Arrangements for discharge from the emergency department that incorporate effective liaison and communications between sectors will contribute to the quality of services for the older person. This will enhance the provision of more efficient aftercare and in the prevention of reoccurrence of health problems and further referral to the emergency department.
Virulence blockers as alternatives to antibiotics: type III secretion inhibitors against Gram‐negative bacteria
Authors: Keyser P. , Elofsson M. , Rosell S. , Wolf‐Watz H.
Published: April 2008

In recent years mounting problems related to antibiotic‐resistant bacteria have resulted in the prediction that we are entering the preantibiotic era. A way of preventing such a development would be to introduce novel antibacterial medicines with modes of action distinct from conventional antibiotics. Recent studies of bacterial virulence factors and toxins have resulted in increased understanding of the way in which pathogenic bacteria manipulate host cellular processes. This knowledge may now be used to develop novel antibacterial medicines that disarm pathogenic bacteria. The type III secretion system (T3SS) is known to be a potent virulence mechanism shared by a broad spectrum of pathogenic Gram‐negative bacteria that interact with human, animal and plant hosts by injecting effector proteins into the cytosol of host cells. Diseases, such as bubonic plague, shigellosis, salmonellosis, typhoid fever, pulmonary infections, sexually transmitted chlamydia and diarrhoea largely depend on the bacterial proteins injected by the T3SS machinery. Recently a number of T3SS inhibitors have been identified using screening‐based approaches. One class of inhibitors, the salicylidene acylhydrazides, has been subjected to chemical optimization and evaluation in several in vitro and ex vivo assays in multiple bacterial species including Yersinia spp., Chlamydia spp., Salmonella spp. and Pseudotuberculosis aeruginosa. Reports published up to date indicate that T3SS inhibitors have the potential to be developed into novel antibacterial therapeutics.
Selective blockade of NF‐κB by novel mutated IκBα suppresses CD3/CD28‐induced activation of memory CD4+ T cells in asthma
Authors: Zhou L.‐F. , Zhang M.‐S. , Hu A.‐H. , Zhu Z. , Yin K.‐S.
Published: April 2008

Background:  Nuclear factor κB (NF‐κB) overactivation plays a crucial role in T‐helper 2 (Th2)‐biased allergic airway inflammation by increased activation and decreased apoptosis of CD4+ T cells. We have shown that targeted NF‐κB suppression in dendritic cells by adenoviral gene transfer of a novel mutated inhibitor of NF‐κB (IκBα) (AdIκBαM) contributes to T‐cell tolerance, but the immunosuppressive action of AdIκBαM on memory (CD45RO+) CD4+ T cells remains enigmatic.

Methods:  CD45RO+ T cells from Dermatophagoides farinaei‐sensitized asthmatic patients, untransfected or transfected with AdIκBαM or AdLacZ (β‐galactosidase) for 24 h, were stimulated with anti‐CD3 (1.0 μg/ml) plus anti‐CD28 (0.5 μg/ml) monoclonal antibody for an additional 24 h. IκBαM transgene expression and NF‐κB activation were detected by polymerase chain reaction (PCR), reverse transcription‐PCR (RT‐PCR), Western blot analysis, and electrophoretic mobility shift assay. Phenotype and apoptosis were measured by flow cytometry, annexin V binding, and terminal deoxyribonucleotidyl transferase‐mediated dUTP nick end labeling analyses. Cytokine production and cell proliferation were determined using enzyme‐linked immunosorbent assay and [3H] thymidine incorporation.

Results:  A unique 801‐bp IκBαM cDNA and a dose‐dependent increase in IκBαM transgene expression were observed in AdIκBαM‐transfected CD45RO+ T cells. Significantly, AdIκBαM inhibited CD3/CD28‐mediated NF‐κB activation in CD45RO+ T cells, leading to evident apoptosis, reduction of eotaxin, RANTES, Th1 [interferon (IFN)‐γ and interleukin (IL)‐2], and Th2 (IL‐4, IL‐5, and IL‐13 despite a slight decrease in IL‐10) cytokines and secondary proliferative response. AdIκBαM also upregulated cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4) and downregulated CD69 besides no change in CD28.

Conclusion:  IκBαM might be beneficial to augment memory CD4+ T‐cell tolerance through modulating B7‐CD28/CTLA‐4 co‐stimulatory pathways and NF‐κB‐dependent cytokine profiles in allergic inflammatory diseases including asthma.
Lack of control of severe asthma is associated with co‐existence of moderate‐to‐severe rhinitis
Authors: Ponte E. V. , Franco R. , Nascimento H. F. , Souza‐Machado A. , Cunha S. , Barreto M. L. , Naspitz C. , Cruz Á. A.
Published: April 2008

Background:  Retrospective studies provide evidence that rhinitis is associated with more severe asthma. The aim of this study was to evaluate prospectively whether rhinitis is a predictor of increased asthma severity.

Methods:  Five hundred and fifty‐seven patients with severe asthma were enrolled. During 1 year of follow‐up, each patient was evaluated every 3 months with a record of emergency room visits and supply of topical corticosteroids for asthma and rhinitis. In the 1 year of follow‐up visit, the patients were checked for rhinitis diagnosis, severity and answered questionnaires for asthma symptoms and quality of life.

Results:  Eighty‐two (15%) patients had no rhinitis, 299 (54%) had mild rhinitis and 176 (31%) moderate/severe rhinitis. In logistic regression models, moderate/severe rhinitis was a predictor for any emergency room visit in the follow‐up period [3.83 (2.00–7.35)], for the presence of uncontrolled asthma after 1 year of follow‐up [12.68 (1.73–92.85)], for <10% improvement of the airway obstruction [2.94 (1.48–5.85)] and <50% reduction in the number of emergency room visits [2.90 (1.02–8.26)] in the year of follow‐up. It was also associated with a smaller chance of more than 90% reduction in the number of emergency room visits in the year of follow‐up [0.27 (0.12–0.60)]. In a multivariate linear regression model, severity of rhinitis was positively correlated with a score of asthma severity and inversely correlated to an index of quality of life.

Conclusions:  In a population with severe asthma, moderate/severe rhinitis is a strong predictor for greater severity of asthma.
Quality‐of‐life and asthma‐severity in general population asthmatics: results of the ECRHS II study
Authors: Siroux V. , Boudier A. , Anto J. M. , Cazzoletti L. , Accordini S. , Alonso J. , Cerveri I. , Corsico A. , Gulsvik A. , Jarvis D. , De Marco R. , Marcon A. , Marques E. A. , Bugiani M. , Janson C. , Leynaert B. , Pin I.
Published: April 2008

Background:  Health‐related quality‐of‐life (HRQL) has been poorly studied in large samples of asthmatics from the general population. HRQL and its relationship to asthma‐severity were assessed among 900 asthmatics enrolled in the European Community Respiratory Health Survey.

Methods:  Among asthmatics, 864 completed the short form‐36 (SF‐36) questionnaire and 477 also completed the Asthma Quality‐of‐life Questionnaire (AQLQ). A 4‐class asthma‐severity scale, combining clinical items, forced expiratory volume in 1 s and the level of treatment and the different asthma‐severity components (each of the clinical items and hospitalization) were studied in relation to HRQL.

Results:  Mean SF‐36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores (45.5 and 48.8 respectively) were lower than expected in a general population. The mean total AQLQ score was 5.8. The AQLQ score and to a lesser extent the PCS score were significantly related to the 4‐class asthma‐severity scale, although the risk of having a lower HRQL score did not vary proportionally across the levels of severity. Asthma‐severity had no impact on the MCS score. Asthma attack frequency and hospitalization were associated with both total AQLQ and PCS scores, whereas nocturnal symptoms and lung function were more strongly related to the AQLQ and PCS score respectively.

Conclusion:  In population‐based asthmatics, the specific AQLQ questionnaire, and also to a lesser extent the generic SF‐36 questionnaire, were sensitive to asthma‐severity. Frequencies of asthma attacks, of nocturnal symptoms and hospitalization for asthma have independent impact on HRQL.
Airway remodeling is correlated with obstruction in children with severe asthma
Authors: Tillie‐Leblond I. , De Blic J. , Jaubert F. , Wallaert B. , Scheinmann P. , Gosset P.
Published: April 2008

Background:  Severe asthma may involve an irreversible obstructive pattern, and structural changes in bronchial airways are believed to play a key role in this context. The aim of the present study was to compare airway remodeling in severe asthmatic children with or without obstructive pattern.

Methods:  Two groups of children with severe asthma and persistent symptoms, 5–14 years old were included, 15 with persistent obstructive pattern (group O) and 10 without obstructive pattern (group N). Persistent obstructive pattern was defined as a forced expiratory volume in 1 s (FEV1) less than 80% of the predicted value after a course of systemic corticosteroids and no significant improvement after bronchodilator. We examined bronchial biopsies by pathological and immunochemical methods and quantified airway smooth muscle (ASM) and mucus gland areas, reticular basement membrane (RBM) thickening, distance between ASM and RBM, muscle light chain kinase (MLCK) expression and number of vessels (CD31 expression).

Results:  Surface area of ASM (P = 0.009), MLCK expression (P = 0.03) and number of vessels (P = 0.0008) were increased in group O compared with group N. Distance of RBM–ASM was shorter in group O (P = 0.007). FEV1 negatively correlated with ASM area (r = −0.6; P = 0.002), MLCK expression (r = −0.45; P = 0.02) and CD31 expression (r = −0.7; P = 0.0003), and positively correlated with the distance of RBM–ASM (r = 0.5; P = 0.007).

Conclusions:  Structural abnormalities of airway remodeling are present in children with severe asthma. Only an increase in surface area of ASM and the density of the vascular network are more pronounced in children with persistent obstructive pattern, while RBM thickening is similar. These results are concordant with longitudinal studies which emphasize the precocity of bronchial obstruction.
Mutation screening of the CARD15 gene in sarcoidosis
Authors: Akahoshi M. , Ishihara M. , Namba K. , Kitaichi N. , Ando Y. , Takenaka S. , Ishida T. , Ohno S. , Mizuki N. , Nakashima H. , Shirakawa T.
Published: April 2008

CARD15 was first identified as a susceptibility gene for Crohn’s disease. More recently, CARD15 mutations were shown to be associated with the pediatric granulomatous inflammatory diseases, Blau syndrome and early‐onset sarcoidosis (EOS). The aim of the present study was to evaluate whether CARD15 variants also play a role in patients with ordinary sarcoidosis other than EOS. We enrolled 135 Japanese sarcoidosis patients with uveitis as well as 95 healthy individuals and performed mutation analysis by direct sequencing of CARD15 exon 4. Direct DNA sequencing in the sarcoidosis patients showed eight CARD15 variants, including five novel mutations (13402C>T, 13543C>T, 13775C>A, 13937G>A, and 14079C>T). Compared with healthy individuals, CARD15 mutations are not common in the Japanese patients with sarcoidosis. Based on the results, we examined the clinical manifestations in patients with sarcoidosis according to their CARD15 mutations. Sarcoidosis patients with these mutations have no specific clinical features with regard to course of the disease or disease severity. Our results indicate that in general, CARD15 mutations may not contribute to the risk of sarcoidosis.
Identification of 11 novel HLA alleles found during typing of unrelated registry donors in China
Authors: Shan X. , Xiao Y. , Wang L. , Lazaro A. M. , Hurley C. K.
Published: April 2008

Eleven novel human leukocyte antigen (HLA) alleles were identified during routine sequence‐specific oligonucleotide probe (SSOP) typing (LABType®; One Lambda Inc., Los Angeles, CA) of volunteers for a hematopoietic stem cell registry in Beijing, China. The new alleles were detected when one or more probes gave an unexpected reactivity pattern.
Cold storage of pooled, buffy‐coat‐derived, leucoreduced platelets in plasma
Authors: Hornsey V. S. , Drummond O. , McMillan L. , Morrison A. , Morrison L. , MacGregor I. R. , Prowse C. V.
Published: April 2008

Background  This study was designed to determine which in vitro assays would be most useful for studying the effects of cold storage on platelet concentrates and to establish an in vivo model for platelet recovery and survival.

Study Design and Methods  Paired, plasma‐suspended, leucoreduced, buffy‐coat‐derived platelet concentrates were stored either at 22 or 4°C. Prior to storage and after 18 h, 5 days and 7 days, samples were taken and various assays were performed. On day 6, in vivo studies were carried out using a model system. Galactosylation of the platelets, prior to cold storage, was also tested.

Results  Hypotonic shock response, collagen‐induced aggregation, RANTES and P‐selectin binding site measurements demonstrated differences between platelets stored at 22 and 4°C. The glycocalicin assay was able to demonstrate microvesicle formation at 4°C. The in vivo model showed that there was at least a 50% decrease in recovery and survival when the platelets were stored in the cold. Galactosylation did not improve these results.

Conclusions  Several assays, both in vitro and in vivo, were able to detect differences in platelet‐storage characteristics and in vivo recovery and survival in a model system. Galactosylation did not correct these cold‐induced changes.
The small genome of an abundant coastal ocean methylotroph
Authors: Giovannoni Stephen J. , Hayakawa Darin H. , Tripp H. James , Stingl Ulrich , Givan Scott A. , Cho Jang‐Cheon , Oh Hyun‐Myung , Kitner Joshua B. , Vergin Kevin L. , Rappé Michael S.
Published: April 2008

OM43 is a clade of uncultured β‐proteobacteria that is commonly found in environmental nucleic acid sequences from productive coastal ocean ecosystems, and some freshwater environments, but is rarely detected in ocean gyres. Ecological studies associate OM43 with phytoplankton blooms, and evolutionary relationships indicate that they might be methylotrophs. Here we report on the genome sequence and metabolic properties of the first axenic isolate of the OM43 clade, strain HTCC2181, which was obtained using new procedures for culturing cells in natural seawater. We found that this strain is an obligate methylotroph that cannot oxidize methane but can use the oxidized C1 compounds methanol and formaldehyde as sources of carbon and energy. Its complete genome is 1304 428 bp in length, the smallest yet reported for a free‐living cell. The HTCC2181 genome includes genes for xanthorhodopsin and retinal biosynthesis, an auxiliary system for producing transmembrane electrochemical potentials from light. The discovery that HTCC2181 is an extremely simple specialist in C1 metabolism suggests an unanticipated, important role for oxidized C1 compounds as substrates for bacterioplankton productivity in coastal ecosystems.
Hypoxia‐inducible factor‐2α: effect on radiation sensitivity and differential regulation by an mTOR inhibitor
Authors: Bhatt Rupal S. , Landis Daniel M. , Zimmer Michael , Torregrossa Joelle , Chen Shaoyong , Sukhatme Vikas P. , Iliopoulos Othon , Balk Steve , Bubley Glenn J.
Published: April 2008

OBJECTIVE

To determine the role of hypoxia‐inducible factor‐2α (HIF2α) on the sensitivity of renal cell carcinoma (RCC) cell lines to ionizing radiation and to determine if the mTOR antagonist, rapamycin, could decrease HIF2α protein levels.

MATERIALS AND METHODS

Cell lines expressing stable short‐hairpin RNAs (shRNAs) encoding HIF2α shRNAs or an empty vector were transfected with a hypoxia responsive element (HRE)‐driven firefly luciferase reporter gene. Two separate paired cell lines were assayed for their response to increasing doses of ionizing radiation. Proliferation and cell cycle kinetics were compared for cell lines expressing HIF2α shRNAs and empty vectors. The effect of an mTOR antagonist, rapamycin on HIF1α and HIF2α proteins levels was also assessed.

RESULTS

We confirmed that the 786‐O RCC lines with stably integrated shRNAs against HIF2α had decreased activation of a plasmid with a HRE‐driven firefly luciferase reporter gene. Lines from two separate cell clones with decreased HIF2α levels showed a significant increase in radiation sensitivity and an increase in G2 cell cycle arrest. Rapamycin, while effective in decreasing HIF1α protein levels, did not affect HIF2α levels in either of the RCC cell lines.

CONCLUSIONS

These results show that decreasing levels of HIF2α leads to an increased sensitivity to ionizing radiation. This finding may explain in part, the known resistance of RCC to radiation therapy. Although mTOR antagonists are approved for the treatment of RCC, these agents do not decrease HIF2α levels and therefore might not be effective in enhancing the radio‐sensitivity of these tumours.
Allocating Resources in an Uncertain World: Water Management and Endangered Species
Authors: Woodward Richard T. , Shaw W. Douglass
Published: April 2008

Instream flows may be essential in protecting aquatic species that are threatened or endangered. An economic model of the optimal allocation of water under pure uncertainty is developed, with particular attention paid to the situation when a species characterized by critical depensation is affected by instream flows. We adopt the notion of pure uncertainty that Frank Knight and Daniel Ellsberg intended, which applies when decision makers cannot reduce their uncertainty to a unique probability distribution. Following recent work by Hansen, Sargent, and others, we employ robust control as a way to deal with this problem.
Water Markets and Third‐Party Effects
Authors: Bourgeon Jean-Marc , Easter K. William , Smith Rodney B.W.
Published: April 2008

We examine potential third‐party effects arising from trading water from one region (rural) to another (urban). Using labor, water and heterogeneous land, rural agents produce a traded agricultural good and nontraded service good. Absent job market frictions, increased water trading improves per capita regional welfare, but aggregate service income can increase (decrease) while individual land rents decrease (increase). If labor experiences job market frictions, water trading can trigger socially inefficient land fallowing, and a decrease in per capita regional welfare. Simulation results confirm the no‐job‐market‐friction model predictions.
Economic Development Prospects of Forest‐Dependent Communities: Analyzing Trade‐offs Using a Compromise‐Fuzzy Programming Framework
Authors: Krcmar Emina , van Kooten G. Cornelis
Published: April 2008

Many aboriginal communities look to forest resources for short‐ and long‐term employment, adequate timber for mills, an even flow of wood fiber for community stability, and financial returns for economic diversification. We address these conflicting objectives using multiple‐objective programming. We show how compromise programming can be used to set bounds on fuzzy membership functions, and illustrate the difference between crisp and fuzzy weighting of objectives. Economic development outcomes obtained using compromise and fuzzy programming greatly improve upon those associated with the even‐flow of timber rule of thumb. Yet, timber extraction is an inadequate driver of economic development in rural communities.
A South–South Survival Strategy: The Potential for Trade among Developing Countries
Authors: Fugazza Marco , Vanzetti David
Published: April 2008

Trade between developing countries, or South–South trade, has been growing rapidly in recent years following reductions in tariff barriers. However, significant barriers remain, and there is currently reluctance in many developing countries to undertake further reductions, with a preference instead for focusing on opening up access to developed country markets, or maintaining the status quo given that multilateral liberalisation may result in the erosion of preferential access enjoyed by some developing countries. This emphasis on Northern markets represents a missed opportunity for developing countries. To assess this we compare the potential effects of the removal of barriers on South–South trade with the gains from developed country liberalisation and from regional free trade areas within Africa, Asia and Latin America. A general equilibrium model, the Global Trade Analysis Project (GTAP) model, containing information on preferential bilateral tariffs, is used to estimate the impacts. The results indicate that the opening up of Northern markets would provide annual welfare gains to developing countries of $22 billion. However, the removal of South–South barriers has the potential to generate gains 40 per cent larger. The results imply that giving greater emphasis to removing barriers between as well as within continents could prove a successful Southern survival strategy.
The Trade Effects of the EU–Turkey Customs Union
Authors: Adam Antonis , Moutos Thomas
Published: April 2008

In the present study we argue that the salient features of both the EU‐15 countries and Turkey are conducive to making the effects of the 1995 EU–Turkey customs union asymmetric among the incumbent EU countries. In order to support our argument we rely on a model in which trade involves the exchange of vertically differentiated products. This model generates the prediction that the more contiguous an incumbent country is to the joining country in terms of technological sophistication, the larger will be the crowding out of this country's exports to the other incumbent countries as a result of the CU expansion. Using a gravity model we estimate the effects of the customs union between Turkey and the EU‐15 by differentiating between exports from (a) lower‐technology EU‐15 countries (we term this group of countries ‘South’) to higher‐technology EU‐15 countries (the ‘North’), (b) North to South, (c) South to Turkey, (d) North to Turkey, and (e) Turkey to EU‐15. Our econometric results indicate that, in contrast to North's exports to the other EU‐15 countries (which have remained intact), the Southern countries’ exports to the other EU‐15 countries have declined as a result of the CU. Moreover, the extra penetration of the Turkish market by the EU‐15 countries has not been more favourable to the Southern group.
The Electoral Impact of Direct‐Democratic Practices
Authors: ANDUIZA EVA , FONT JOAN , MAS PAU , DE MAYA SERGI
Published: April 2008

In recent years there has been a growing interest in the integration of mechanisms of direct citizen participation in the institutional structure of representative democracy, particularly at the local level. This essay examines the electoral impact of mechanisms of direct citizen participation. Although it is often considered that participatory schemes can be a means to achieve electoral success in the hands of politicians seeking re‐election, quantitative analyses of 65 Spanish municipalities demonstrate that electoral success is far from being an immediate consequence of direct democratic practices (DDPs). The qualitative analysis of four cases shows that electoral consequences directly attributable to participatory devices depend on their design and on how they fit into the whole political process. Participatory processes that are too rigid and those, especially, that generate expectations that cannot be translated into real policies may end up having a negative effect. On the other hand, DDPs may account for network‐building and improved information among citizens that, in turn, may have electoral consequences. DDPs are thus neither a blessing nor a cure per se in their electoral effects. Instead, as with representative democracy, their consequences and success will ultimately depend upon their procedural dimension.

Ces dernières années ont connu un intérêt croissant pour l’intégration de mécanismes de participation directe des citoyens dans le cadre institutionnel de la démocratie participative, notamment au niveau local. Cet article examine l’impact électoral des mécanismes de participation directe. Même si on estime souvent que les systèmes participatifs peuvent permettre la victoire d’hommes politiques en quête de réélection, des analyses quantitatives sur 65 municipalités espagnoles montrent que le succès électoral est loin de résulter automatiquement des pratiques de démocratie directe (PDD). L’analyse qualitative de quatre cas révèle que les incidences électorales imputables directement aux dispositifs participatifs dépendent du concept utilisé et de la manière dont ceux‐ci s’intègrent dans le processus politique global. Si les démarches participatives sont trop rigides, et notamment si elles suscitent des attentes qui ne peuvent se traduire dans des politiques publiques concrètes, elles sont susceptibles d’avoir, en fin de compte, un effet négatif. En revanche, les PDD peuvent expliquer la construction de réseaux et l’amélioration de l’information entre les citoyens, ce qui peut influer sur des élections. Les PDD ne sont donc ni une bénédiction ni une malédiction en termes d’incidences électorales. A l’instar de celles de la démocratie représentative, leurs conséquences et leur réussite vont finalement dépendre de leur dimension procédurale.
Association between oral lichenoid reactions and amalgam restorations
Authors: Pezelj‐Ribarić S , Prpić J , Miletić I , Brumini G , Šoškić M Šimunović , Anić I
Published: April 2008

Background  The aim of this study was to perform a clinical assessment of the association between oral lichenoid reactions (OLR) and amalgam restorations and to determine the salivary concentrations of interleukin‐6 (IL‐6) and IL‐8 before and after replacement of the amalgam restorations.

Methods  The study included 20 patients with OLR and 20 healthy volunteers, who were examined between 2001 and 2005 at the Oral Medicine Unit of the Medical Faculty University of Rijeka. All patients were skin patch tested by an experienced physician. Saliva samples were collected, prepared and analysed for IL‐6 and IL‐8 concentrations using enzyme‐linked immunosorbent assay.

Results  Sixteen out of 20 patch‐tested patients showed a sensitization to inorganic mercury or amalgam. Total replacement of all amalgam fillings was carried out on 20 patients with fillings based on composite resin, gold, porcelain or a combination of these. Sixteen out of 20 patients showed complete healing of OLR; three patients had marked improvement, whereas one patient showed no improvement. Levels of IL‐6 detected before replacement were significantly higher than IL‐6 levels following the replacement (P = 0.003). The IL‐8 levels measured before replacement procedure were significantly higher than the IL‐8 levels after replacement of the fillings (P < 0.001).

Conclusions  On the basis of clinical observations, restorative therapy resulted in tissue healing. Following the replacement of amalgam fillings with fillings based on other restorative materials, levels of both IL‐6 and IL‐8 shifted towards normal, as measured in healthy subjects.
DEVELOPMENTAL CHANGES IN TRAIT AND SITUATIONAL DENIAL UNDER STRESS DURING CHILDHOOD
Authors: Smith Wendy P. , Rossman B. B. Robbie
Published: April 2008

Abstract— Decline in denial usage during childhood was examined by obtaining four measures of denial from 34, 6‐, 8‐ and 10‐year‐old boys. Significant age declines were observed for two trait denial measures and one situational denial measure. Positive relationships among denial measures were observed only for the trait measures. It appears that knowledge of trait denial may not be very useful in predicting situational denial; and that future research should be directed toward more detailed examination of cognitive processes associated with defensive outcomes and toward changes in external factors, such as peer evaluation of defensive behaviors, which could impact on the production of defensive responses.