bluuebunny/crossref_metadata_2025 huggingface dataset:
Desirable performance characteristics for BCR-ABL measurement on an international reporting scale to allow consistent interpretation of individual patient response and comparison of response rates between clinical trials
Authors: Branford Susan , Fletcher Linda , Cross Nicholas C. P. , Müller Martin C. , Hochhaus Andreas , Kim Dong-Wook , Radich Jerald P. , Saglio Giuseppe , Pane Fabrizio , Kamel-Reid Suzanne , Wang Y. Lynn , Press Richard D. , Lynch Kevin , Rudzki Zbigniew , Goldman John M. , Hughes Timothy
Published: August 2008

An international basis for comparison of BCR-ABL mRNA levels is required for the common interpretation of data derived from individual laboratories. This will aid clinical decisions for individual patients with chronic myeloid leukemia (CML) and assist interpretation of results from clinical studies. We aligned BCR-ABL values generated by 38 laboratories to an international scale (IS) where a major molecular response (MMR) is 0.1% or less. Alignment was achieved by application of laboratory-specific conversion factors calculated by comparisons performed with patient samples against a reference method. A validation procedure was completed for 19 methods. We determined performance characteristics (bias and precision) for consistent interpretation of MMR after IS conversion. When methods achieved an average BCR-ABL difference of plus or minus 1.2-fold from the reference method and 95% limits of agreement within plus or minus 5-fold, the MMR concordance was 91%. These criteria were met by 58% of methods. When not met, the MMR concordance was 74% or less. However, irrespective of precision, when the bias was plus or minus 1.2-fold as achieved by 89% of methods, there was good agreement between the overall MMR rates. This indicates that the IS can deliver accurate comparison of molecular response rates between clinical trials when measured by different laboratories.
Sleep-disordered breathing in unilateral diaphragm paralysis or severe weakness
Authors: Steier J. , Jolley C. J. , Seymour J. , Kaul S. , Luo Y. M. , Rafferty G. F. , Hart N. , Polkey M. I. , Moxham J.
Published: August 2008

Few data exist concerning sleep in patients with hemidiaphragm paralysis or weakness. Traditionally, such patients are considered to sustain normal ventilation in sleep.

In the present study, diaphragm strength was measured in order to identify patients with unilateral paralysis or severe weakness. Patients underwent polysomnography with additional recordings of the transoesophageal electromyogram (EMG) of the diaphragm and surface EMG of extra-diaphragmatic respiratory muscles. These data were compared with 11 normal, healthy subjects matched for sex, age and body mass index (BMI).

In total, 11 patients (six males, mean±sdage 56.5±10.0 yrs, BMI 28.7±2.8 kg·m−2) with hemidiaphragm paralysis or severe weakness (unilateral twitch transdiaphragmatic pressure 3.3±1.7 cmH2O (0.33±0.17 kPa) were studied. They had a mean±sdrespiratory disturbance index of 8.1±10.1 events·h−1during non-rapid eye movement (NREM) sleep and 26.0±17.8 events·h−1during rapid eye movement (REM) sleep (control groups 0.4±0.4 and 0.7±0.9 events·h−1, respectively). The diaphragm EMG, as a percentage of maximum, was double that of the control group in NREM sleep (15.3±5.3versus8.9±4.9% max, respectively) and increased in REM sleep (20.0±6.9% max), while normal subjects sustained the same level of activation (6.2±3.1% max).

Patients with unilateral diaphragm dysfunction are at risk of developing sleep-disordered breathing during rapid eye movement sleep. The diaphragm electromyogram, reflecting neural respiratory drive, is doubled in patients compared with normal subjects, and increases further in rapid eye movement sleep.
Fluticasone propionate reduces bacterial airway epithelial invasion
Authors: Barbier M. , Agustí A. , Albertí S.
Published: August 2008

Fluticasone propionate reduces the frequency and severity of the episodes of exacerbation of chronic obstructive pulmonary disease (COPD).Streptococcus pneumoniaeandHaemophilus influenzaeare frequently isolated in these episodes. Both express phosphorylcholine, an epitope that mediates their interaction with airway epithelial cellsviathe platelet-activating factor receptor (PAFR).

The present work studies the effects of fluticasone propionate on the expression of PAFR on human airway epithelial cells, the invasion of these cells byS. pneumoniaeandH. influenzae, and the course of pneumococcal infectionin vivo. The following were used in the experiments:S. pneumoniaeandH. influenzaeisolated from patients with COPD, cell cultures of type II pneumocytes and bronchoepithelial cells, and a mouse model of lung infection.

Fluticasone propionate was found to reduce PAFR expression on the surface of the two cells types studied. AllS. pneumoniaeandH. influenzaeisolates expressed phosphorylcholine. Treatment of both cells lines with fluticasone propionate reduced invasion of both microorganisms and reduced the bacterial load of mice infected withS. pneumoniae.

Fluticasone propionate reduces the invasion of airway epithelial cells byStreptococcus pneumoniaeandHaemophilus influenzaethrough its effect on platelet-activating factor receptor. These results may help explain the beneficial effects of fluticasone propionate on chronic obstructive pulmonary disease exacerbations.
Antenatal infection in the rabbit impairs post-natal growth and lung alveolarisation
Authors: Gras-Le Guen C. , Denis C. , Franco-Montoya M-L. , Jarry A. , Delacourt C. , Potel G. , Bourbon J. , Roze J-C. , Jarreau P-H.
Published: August 2008

Clinical and experimental studies indicate an association between chorioamnionitis and bronchopulmonary dysplasia in preterm infants. The present authors hypothesised that, in the rabbit, antenatal infection may impair lung development after birth, despite effective maternal antibiotic therapy.

Pregnant rabbits received an intra-uterine inoculation of 103Escherichia colicolony forming units or vehicle at the end of gestation (day 29). Intravenous ceftriaxone therapy was initiated 8 h after inoculation for a period of 8 days. Pups born between 60 and 84 h after inoculation were kept with their mother until sacrifice on days 0, 1, 5, 8 and 15.

Blood cultures from antenatally infected animals were sterile at birth. Postnatal growth was significantly impaired by day 8. Lung morphometry showed a significant decrease of alveolar surface density and interstitial density, with a significant increase of alveolar airspace volume, indicating impaired alveolarisation for the first 2 weeks of postnatal life. Inflammatory and apoptotic processes were not detected in the lung at birth or subsequently.

Intra-uterine infection in rabbits is, therefore, responsible for concomitant postnatal growth retardation and abnormal pulmonary development despite early and effective antenatal antibiotic therapy. This may constitute an alternative model to study the consequences of antenatal infection on postnatal growth and lung development.
Comparison of tuberculosis surveillance systems in low-incidence industrialised countries
Authors: Mor Z. , Migliori G. B. , Althomsons S. P. , Loddenkemper R. , Trnka L. , Iademarco M. F.
Published: August 2008

The comparative analysis of National Tuberculosis Control Programmes (NTPs) in industrialised, low-tuberculosis-incidence countries is limited. Analysis of applied methods, function and accumulated experience contributes to improving global tuberculosis control.

A questionnaire addressing NTP surveillance infrastructure and characteristics was completed in 19 industrialised countries, with populations of >3 million and annual notified tuberculosis incidence rates of <16 cases per 100,000 population (2003 data).

All European countries surveyed adopted World Health Organization Collaborating Centre for the Surveillance of Tuberculosis in Europe (EuroTB) definitions. Surveillance information, which usually includes names, was transferred electronically to the national level in 17 out of the 19 countries. Surveillance systems capture process and social determinants. Case notification to the central level occurred within a median period of 7 days, independent of mandatory notification requirements. The mean completeness of tuberculosis case-reporting was estimated to be 93.5% (range 65–100%). Integration between HIV and tuberculosis registries was performed in two countries, and, in seven others, both databases were cross-matched periodically.

National Tuberculosis Control Programme function in industrialised low-incidence countries utilises well-established infrastructure and relies upon centralised operations. Approaches are consistent with current World Health Organization surveillance recommendations. The present study lays collaborative groundwork for additional multinational analyses for the enhancement of global tuberculosis surveillance, which may assist policy-makers in countries moving from medium to low rates of incidence.
Evaluating the potential of IP-10 and MCP-2 as biomarkers for the diagnosis of tuberculosis
Authors: Ruhwald M. , Bodmer T. , Maier C. , Jepsen M. , Haaland M. B. , Eugen-Olsen J. , Ravn P.
Published: August 2008

The aim of the present study was to evaluate the potential of diagnostic tests based on interferon-γ inducible protein (IP)-10 and monocyte chemotactic protein (MCP)-2, and compare the performance with the QuantiFERON TB® Gold In-Tube (QFT-IT; Cellestis, Carnagie, Australia) test.

IP-10 and MCP-2 were determined in supernatants from whole blood stimulated withMycobacterium tuberculosis-specific antigens. Samples were obtained from 80 patients with culture- and/or PCR-proven tuberculosis (TB), and 124 unexposed healthy controls: 86 high school students and 38 high school staff. IP-10 and MCP-2 test cut-offs were established based on receiver operating characteristic curve analysis.

TB patients produced significantly higher levels (median) of IP-10 (2158 pg·mL−1) and MCP-2 (379 pg·mL−1) compared with interferon (IFN)-γ (215 pg·mL−1). The QFT-IT, IP-10 and MCP-2 tests detected 81, 83 and 71% of the TB patients; 0, 3 and 0% of the high school students and 0, 16 and 3% of the staff, respectively. Agreement between tests was high (>89%). By combining IP-10 and IFN-γ tests, the detection rate increased among TB patients to 90% without a significant increase in positive responders among the students.

In conclusion, interferon-γ inducible protein-10 and monocyte chemotactic protein-2 responses toMycobacterium tuberculosis-specific antigens could be used to diagnose infection. Combining interferon-γ inducible protein-10 and interferon-γ may be a simple approach to increase the detection rate of theMycobacterium tuberculosis-specificin vitrotests.
Computed tomography assessment of lung volume changes after bronchial valve treatment
Authors: Coxson H. O. , Nasute Fauerbach P. V. , Storness-Bliss C. , Müller N. L. , Cogswell S. , Dillard D. H. , Finger C. L. , Springmeyer S. C.
Published: August 2008

The aim of the present study was to correlate clinical outcome measures following treatment with bronchial valves with regional lung volume. Computed tomography (CT) scan data from 57 subjects with severe emphysema were obtained from nine North American clinical trial sites. IBV® Valves (Spiration, Inc., Redmond, WA, USA) were placed to occlude segmental and subsegmental bronchi in right and left upper lobes using a flexible bronchoscope. Subjects completed a St George's Respiratory Questionnaire (SGRQ), pulmonary function test (PFT) and exercise capacity test. CT scans were analysed at baseline and at 1, 3 or 6 months after treatment to measure total and lobar lung density, volume and mass.

Total lung volumes measured using CT were strongly correlated with PFT and did not change with treatment. However, the treated upper lobes significantly decreased in volume in 88% of the observations, by mean±sd335±444 mL, or a decrease of 10.2% in the 6 month data. The untreated lobes had an 11.6% increase in volume. Changes in regional lung volume were associated with clinically meaningful improvements in SGRQ (-8.95±16.22), but not clinically meaningful PFT changes.

The significant health status improvements reported by subjects following bilateral bronchial valve treatment are associated with regional lung volume changes and interlobar shift measured using computed tomography.
ExoU-induced procoagulant activity inPseudomonas aeruginosa-infected airway cells
Authors: Plotkowski M. C. , Feliciano L. F. P. , Machado G. B. S. , Cunha L. G. , Freitas C. , Saliba A. M. , de Assis M. C.
Published: August 2008

The present study addressed the question whether ExoU, aPseudomonas aeruginosatoxin with phospholipase A2 (PLA2) activity, may induce airway epithelial cells to overexpress tissue factor (TF) and exhibit a procoagulant phenotype.

Cells from the human bronchial epithelial BEAS-2B line were infected with an ExoU-producingP. aeruginosastrain, pre-treated or not with the cytosolic PLA2 inhibitor methylarachidonyl fluorophosphate (MAFP), or with two ExoU-deficient mutants. Control noninfected and infected cells were assessed for the expression of: 1) TF mRNA by RT-PCR; 2) cell-associated TF by enzyme immunoassay and flow cytometry; 3) procoagulant activity by a colorimetric assay; and 4) microparticle-associated TF by flow cytometry. An enzyme immunoassay was also used to assess cell-associated TF in lung extracts from mice infected intratracheally with ExoU-producing and -deficient bacteria.

Cells infected with the wild-type bacteria had higher levels of TF mRNA, cell-associated TF expression, procoagulant activity and released microparticle-associated TF than cells infected with the mutants. Bacterial treatment with MAFP significantly reduced the expression of TF by infected cells. Lung samples from mice infected with the wild-type bacteria exhibited higher levels of cell-associated TF and procoagulant activity.

The present results demonstrate that ExoU may contribute to the pathogenesis of lung injury by inducing a tissue factor-dependent procoagulant activity in airway epithelial cells.
The response to combination therapy treatment regimens in severe/difficult-to-treat asthma
Authors: Campbell J. D. , Borish L. , Haselkorn T. , Rasouliyan L. , Lee J. H. , Wenzel S. E. , Sullivan S. D.
Published: August 2008

The aim of the present study was to assess the response of high-dose salmeterol/fluticasone combination (SFC) and low-dose SFC compared with regimens without inhaled corticosteroid (ICS) plus long-acting β-agonist (LABA) in a large cohort with severe or difficult-to-treat asthma.

Subjects were administered low-dose SFC (100/50 or 250/50 μg) or high-dose SFC (500/50 μg), and a control group received medications that could include ICS or LABA but not both. The present authors calculated unadjusted and propensity score-adjusted differences in outcomes consistent with components of asthma control, comparing high-dose and low-dose SFC cohorts with controls.

The low-dose SFC cohort had higher asthma-related quality of life and fewer asthma control problems compared with controls. The high-dose SFC cohort had higher forced expiratory volume in one second but higher odds of having severe asthma compared with controls.

The present results support the evidence that some asthmatics achieve better outcomes while receiving a low-dose salmeterol/fluticasone combination, but also suggest that those on a high-dose salmeterol/fluticasone combination fail to achieve significant improvement in many control-related health outcomes as compared with similar patients not receiving salmeterol/fluticasone combination. These findings suggest a limited value of high-dose salmeterol/fluticasone combination compared with the alternatives. While additional studies are needed, the present findings call for alternative therapeutic approaches in severe/difficult-to-treat asthma for those unable to attain asthma control with or without salmeterol/fluticasone combination.
Decreased FOXP3 expression in small airways of smokers with COPD
Authors: Isajevs S. , Taivans I. , Strazda G. , Kopeika U. , Bukovskis M. , Gordjusina V. , Kratovska A.
Published: August 2008

CD4+CD25+ FOXP3-positive T-regulatory cells have an important role in controlling immune and inflammatory reactions. The present authors hypothesise that these cells may be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of the present study was to characterise the expression of FOXP3 in large and small airways of nonsmokers, smokers with normal lung function and COPD patients.

A total of 19 nonsmokers, 20 smokers with normal lung function and 20 smokers with moderate COPD, undergoing lung resection for a solitary peripheral nonsmall cell carcinoma, were enrolled in the study. Immunohistochemical methods were used to evaluate FOXP3 expression in large and small airways.

Smokers with normal lung function and COPD patients had increased numbers of FOXP3-positive cells in large airways compared with nonsmokers. A positive correlation was observed between FOXP3 expression in large airways and smoked pack-yrs. In small airways, COPD patients had decreased numbers of FOXP3-positive cells, compared with asymptomatic smokers and nonsmokers, that negatively correlated with airflow obstruction.

To conclude, chronic obstructive pulmonary disease is characterised by upregulation of FOXP3-positive cells in large airways but a downregulation in small airways that correlated with airflow limitation. The results of the present study contribute to a better understanding of the pathogenesis of chronic obstructive pulmonary disease.
Physical training does not increase allergic inflammation in asthmatic children
Authors: Moreira A. , Delgado L. , Haahtela T. , Fonseca J. , Moreira P. , Lopes C. , Mota J. , Santos P. , Rytilä P. , Castel-Branco M. G.
Published: August 2008

The effects of a 3-month physical training programme on airway inflammation and clinical outcomes were studied in school-aged children with asthma.

Subjects with persistent allergic asthma (aged 12.7±3.4 yrs; n = 34) were randomly allocated into training and control groups. Exercise consisted of twice-weekly 50-min sessions for 12 weeks. Inflammation was assessed by levels of exhaled nitric oxide, blood eosinophils, eosinophil cationic protein, C-reactive protein, and total and mite-specific immunoglobulin (Ig)E. Lung volumes and bronchial responsiveness to methacholine were determined. The Paediatric Asthma Quality of Life Questionnaire and Paediatric Asthma Caregiver's Quality of Life Questionnaire were used to evaluate activity restrictions, symptoms and emotional stress. The efficacy of the training was assessed by accelerometry.

Following the programme, the exercise group spent twice as much time as the controls undertaking moderate-to-vigorous activities. No differences in changes were seen between groups for asthma outcomes. However, total IgE decreased more in the exercise group, as did mite-specific IgE.

Training did not increase inflammation in children with persistent asthma, and may have decreased both total and allergen-specific immunoglobulin E levels. It is concluded that there is no reason to discourage asthmatic children with controlled disease to exercise.
Changes in lung volumes and airway responsiveness following haematopoietic stem cell transplantation
Authors: Barisione G. , Bacigalupo A. , Crimi E. , Van Lint M. T. , Lamparelli T. , Brusasco V.
Published: August 2008

Changes in lung volume occur following haematopoietic stem cell transplantation (HSCT); airway hyperresponsiveness was occasionally reported, without mechanistic explanation. The present authors studied 17 patients by standard methacholine (MCh) challenge before and then 3 and 12 months after HSCT (n = 16 and n = 13, respectively). Another 6 patients were challenged before and 3 months after HSCT using a modified challenge to investigate the effect of deep inhalations.

No patient developed bronchiolitis obliterans or bronchiolitis obliterans organising pneumonia. At 3 months, forced vital capacity (FVC) was significantly reduced by 0.33±0.55 L, forced expiratory volume in one second (FEV1) by 0.31±0.50 L, total lung capacity (TLC) by 0.39±0.37 L and single-breath diffusing capacity of the lung for carbon monoxide (DL,CO) by 15±12%. At 12 months, TLC decreased by 0.43±0.36 L andDL,COby 8±8%. With standard challenge, no significant changes in FEV1response to MCh were observed after HSCT but FVC decreased significantly less after HSCT compared with prior to HSCT, suggesting less air trapping. With modified challenge, deep inhalations reversed the MCh-induced decrease in partial expiratory flow more after HSCT compared with before HSCT and this correlated with TLC decrements.

In conclusion, an increase in airway responsiveness is unlikely after haematopoietic stem cell transplantation, at least in patients without pulmonary complications, and mechanisms opposing airway narrowing may blunt the bronchoconstrictor response.
The SeqWord Genome Browser: an online tool for the identification and visualization of atypical regions of bacterial genomes through oligonucleotide usage
Authors: Ganesan Hamilton , Rakitianskaia Anna S , Davenport Colin F , Tümmler Burkhard , Reva Oleg N
Published: August 2008

Background

Data mining in large DNA sequences is a major challenge in microbial genomics and bioinformatics. Oligonucleotide usage (OU) patterns provide a wealth of information for large scale sequence analysis and visualization. The purpose of this research was to make OU statistical analysis available as a novel web-based tool for functional genomics and annotation. The tool is also available as a downloadable package.

Results

The SeqWord Genome Browser (SWGB) was developed to visualize the natural compositional variation of DNA sequences. The applet is also used for identification of divergent genomic regions both in annotated sequences of bacterial chromosomes, plasmids, phages and viruses, and in raw DNA sequences prior to annotation by comparing local and global OU patterns. The applet allows fast and reliable identification of clusters of horizontally transferred genomic islands, large multi-domain genes and genes for ribosomal RNA. Within the majority of genomic fragments (also termed genomic core sequence), regions enriched with housekeeping genes, ribosomal proteins and the regions rich in pseudogenes or genetic vestiges may be contrasted.

Conclusion

The SWGB applet presents a range of comprehensive OU statistical parameters calculated for a range of bacterial species, plasmids and phages. It is available on the Internet at http://www.bi.up.ac.za/SeqWord/mhhapplet.php.
Myosin-Vb functions as a dynamic tether for peripheral endocytic compartments during transferrin trafficking
Authors: Provance D William , Addison Erin J , Wood Patrick R , Chen David Z , Silan Colleen M , Mercer John A
Published: August 2008

Background

Myosin-Vb has been shown to be involved in the recycling of diverse proteins in multiple cell types. Studies on transferrin trafficking in HeLa cells using a dominant-negative myosin-Vb tail fragment suggested that myosin-Vb was required for recycling from perinuclear compartments to the plasma membrane. However, chemical-genetic, dominant-negative experiments, in which myosin-Vb was specifically induced to bind to actin, suggested that the initial hypothesis was incorrect both in its site and mode of myosin-Vb action. Instead, the chemical-genetic data suggested that myosin-Vb functions in the actin-rich periphery as a dynamic tether on peripheral endosomes, retarding transferrin transport to perinuclear compartments.

Results

In this study, we employed both approaches, with the addition of overexpression of full-length wild-type myosin-Vb and switching the order of myosin-Vb inhibition and transferrin loading, to distinguish between these hypotheses. Overexpression of full-length myosin-Vb produced large peripheral endosomes. Chemical-genetic inhibition of myosin-Vb after loading with transferrin did not prevent movement of transferrin from perinuclear compartments; however, virtually all myosin-Vb-decorated particles, including those moving on microtubules, were halted by the inhibition. Overexpression of the myosin-Vb tail caused a less-peripheral distribution of early endosome antigen-1 (EEA1).

Conclusion

All results favored the peripheral dynamic tethering hypothesis.
Cold-inducible RNA binding protein (CIRP), a novel XTcf-3 specific target gene regulates neural development in Xenopus
Authors: van Venrooy Stephanie , Fichtner Dagmar , Kunz Martin , Wedlich Doris , Gradl Dietmar
Published: August 2008

Background

As nuclear mediators of wnt/β-catenin signaling, Lef/Tcf transcription factors play important roles in development and disease. Although it is well established, that the four vertebrate Lef/Tcfs have unique functional properties, most studies unite Lef-1, Tcf-1, Tcf-3 and Tcf-4 and reduce their function to uniformly transduce wnt/β-catenin signaling for activating wnt target genes. In order to discriminate target genes regulated by XTcf-3 from those regulated by XTcf-4 or Lef/Tcfs in general, we performed a subtractive screen, using neuralized Xenopus animal cap explants.

Results

We identified cold-inducible RNA binding protein (CIRP) as novel XTcf-3 specific target gene. Furthermore, we show that knockdown of XTcf-3 by injection of an antisense morpholino oligonucleotide results in a general broadening of the anterior neural tissue. Depletion of XCIRP by antisense morpholino oligonucleotide injection leads to a reduced stability of mRNA and an enlargement of the anterior neural plate similar to the depletion of XTcf-3.

Conclusion

Distinct steps in neural development are differentially regulated by individual Lef/Tcfs. For proper development of the anterior brain XTcf-3 and the Tcf-subtype specific target XCIRP appear indispensable. Thus, regulation of anterior neural development, at least in part, depends on mRNA stabilization by the novel XTcf-3 target gene XCIRP.
Initial validation of the Argentinean Spanish version of the PedsQL™ 4.0 Generic Core Scales in children and adolescents with chronic diseases: acceptability and comprehensibility in low-income settings
Authors: Roizen Mariana , Rodríguez Susana , Bauer Gabriela , Medin Gabriela , Bevilacqua Silvina , Varni James W , Dussel Veronica
Published: August 2008

Background

To validate the Argentinean Spanish version of the PedsQL™ 4.0 Generic Core Scales in Argentinean children and adolescents with chronic conditions and to assess the impact of socio-demographic characteristics on the instrument's comprehensibility and acceptability. Reliability, and known-groups, and convergent validity were tested.

Methods

Consecutive sample of 287 children with chronic conditions and 105 healthy children, ages 2–18, and their parents. Chronically ill children were: (1) attending outpatient clinics and (2) had one of the following diagnoses: stem cell transplant, chronic obstructive pulmonary disease, HIV/AIDS, cancer, end stage renal disease, complex congenital cardiopathy. Patients and adult proxies completed the PedsQL™ 4.0 and an overall health status assessment. Physicians were asked to rate degree of health status impairment.

Results

The PedsQL™ 4.0 was feasible (only 9 children, all 5 to 7 year-olds, could not complete the instrument), easy to administer, completed without, or with minimal, help by most children and parents, and required a brief administration time (average 5–6 minutes). People living below the poverty line and/or low literacy needed more help to complete the instrument. Cronbach Alpha's internal consistency values for the total and subscale scores exceeded 0.70 for self-reports of children over 8 years-old and parent-reports of children over 5 years of age. Reliability of proxy-reports of 2–4 year-olds was low but improved when school items were excluded. Internal consistency for 5–7 year-olds was low (α range = 0.28–0.76). Construct validity was good. Child self-report and parent proxy-report PedsQL™ 4.0 scores were moderately but significantly correlated (ρ = 0.39, p < 0.0001) and both significantly correlated with physician's assessment of health impairment and with child self-reported overall health status. The PedsQL™ 4.0 discriminated between healthy and chronically ill children (72.72 and 66.87, for healthy and ill children, respectively, p = 0.01), between different chronic health conditions, and children from lower socioeconomic status.

Conclusion

Results suggest that the Argentinean Spanish PedsQL™ 4.0 is suitable for research purposes in the public health setting for children over 8 years old and parents of children over 5 years old. People with low income and low literacy need help to complete the instrument. Steps to expand the use of the Argentinean Spanish PedsQL™ 4.0 include an alternative approach to scoring for the 2–4 year-olds, further understanding of how to increase reliability for the 5–7 year-olds self-report, and confirmation of other aspects of validity.
Nuclear import of Avian Sarcoma Virus integrase is facilitated by host cell factors
Authors: Andrake Mark D , Sauter Monica M , Boland Kim , Goldstein Andrew D , Hussein Maryem , Skalka Anna Marie
Published: August 2008

Background

Integration of retroviral DNA into the host cell genome is an obligatory step in the virus life cycle. In previous reports we identified a sequence (amino acids 201–236) in the linker region between the catalytic core and C-terminal domains of the avian sarcoma virus (ASV) integrase protein that functions as a transferable nuclear localization signal (NLS) in mammalian cells. The sequence is distinct from all known NLSs but, like many, contains basic residues that are essential for activity.

Results

Our present studies with digitonin-permeabilized HeLa cells show that nuclear import mediated by the NLS of ASV integrase is an active, saturable, and ATP-dependent process. As expected for transport through nuclear pore complexes, import is blocked by treatment of cells with wheat germ agglutinin. We also show that import of ASV integrase requires soluble cellular factors but does not depend on binding the classical adapter Importin-α. Results from competition studies indicate that ASV integrase relies on one or more of the soluble components that mediate transport of the linker histone H1.

Conclusion

These results are consistent with a role for ASV integrase and cytoplasmic cellular factors in the nuclear import of its viral DNA substrate, and lay the foundation for identification of host cell components that mediate this reaction.
Changes in the gene expression profile of Arabidopsis thaliana after infection with Tobacco etch virus
Authors: Agudelo-Romero Patricia , Carbonell Pablo , de la Iglesia Francisca , Carrera Javier , Rodrigo Guillermo , Jaramillo Alfonso , Pérez-Amador Miguel A , Elena Santiago F
Published: August 2008

Background

Tobacco etch potyvirus (TEV) has been extensively used as model system for the study of positive-sense RNA virus infecting plants. TEV ability to infect Arabidopsis thaliana varies among ecotypes. In this study, changes in gene expression of A. thaliana ecotype Ler infected with TEV have been explored using long-oligonucleotide arrays. A. thaliana Ler is a susceptible host that allows systemic movement, although the viral load is low and syndrome induced ranges from asymptomatic to mild. Gene expression profiles were monitored in whole plants 21 days post-inoculation (dpi). Microarrays contained 26,173 protein-coding genes and 87 miRNAs.

Results

Expression analysis identified 1727 genes that displayed significant and consistent changes in expression levels either up or down, in infected plants. Identified TEV-responsive genes encode a diverse array of functional categories that include responses to biotic (such as the systemic acquired resistance pathway and hypersensitive responses) and abiotic stresses (droughtness, salinity, temperature, and wounding). The expression of many different transcription factors was also significantly affected, including members of the R2R3-MYB family and ABA-inducible TFs. In concordance with several other plant and animal viruses, the expression of heat-shock proteins (HSP) was also increased. Finally, we have associated functional GO categories with KEGG biochemical pathways, and found that many of the altered biological functions are controlled by changes in basal metabolism.

Conclusion

TEV infection significantly impacts a wide array of cellular processes, in particular, stress-response pathways, including the systemic acquired resistance and hypersensitive responses. However, many of the observed alterations may represent a global response to viral infection rather than being specific of TEV.
Brain stimulation modulates driving behavior
Authors: Beeli Gian , Koeneke Susan , Gasser Katja , Jancke Lutz
Published: August 2008

Background

Driving a car is a complex task requiring coordinated functioning of distributed brain regions. Controlled and safe driving depends on the integrity of the dorsolateral prefrontal cortex (DLPFC), a brain region, which has been shown to mature in late adolescence.

Methods

In this study, driving performance of twenty-four male participants was tested in a high-end driving simulator before and after the application of transcranial direct current stimulation (tDCS) for 15 minutes over the left or right DLPFC.

Results

We show that external modulation of both, the left and the right, DLPFC directly influences driving behavior. Excitation of the DLPFC (by applying anodal tDCS) leads to a more careful driving style in virtual scenarios without the participants noticing changes in their behavior.

Conclusion

This study is one of the first to prove that external stimulation of a specific brain area can influence a multi-part behavior in a very complex and everyday-life situation, therefore breaking new ground for therapy at a neural level.
Ketamine analgesia for inflammatory pain in neonatal rats: a factorial randomized trial examining long-term effects
Authors: Rovnaghi Cynthia R , Garg Sarita , Hall Richard W , Bhutta Adnan T , Anand K JS
Published: August 2008

Background

Neonatal rats exposed to repetitive inflammatory pain have altered behaviors in young adulthood, partly ameliorated by Ketamine analgesia. We examined the relationships between protein expression, neuronal survival and plasticity in the neonatal rat brain, and correlated these changes with adult cognitive behavior.

Methods

Using Western immunoblot techniques, homogenates of cortical tissue were analyzed from neonatal rats 18–20 hours following repeated exposure to 4% formalin injections (F, N = 9), Ketamine (K, 2.5 mg/kg × 2, N = 9), Ketamine prior to formalin (KF, N = 9), or undisturbed controls (C, N = 9). Brain tissues from another cohort of rat pups (F = 11, K = 12, KF = 10, C = 15) were used for cellular staining with Fos immunohistochemistry or FluoroJade-B (FJB), followed by cell counting in eleven cortical and three hippocampal areas. Long-term cognitive testing using a delayed non-match to sample (DNMS) paradigm in the 8-arm radial maze was performed in adult rats receiving the same treatments (F = 20, K = 24, KF = 21, C = 27) in the neonatal period.

Results

Greater cell death occurred in F vs. C, K, KF in parietal and retrosplenial areas, vs. K, KF in piriform, temporal, and occipital areas, vs. C, K in frontal and hindlimb areas. In retrosplenial cortex, less Fos expression occurred in F vs. C, KF. Cell death correlated inversely with Fos expression in piriform, retrosplenial, and occipital areas, but only in F. Cortical expression of glial fibrillary acidic protein (GFAP) was elevated in F, K and KF vs. C. No significant differences occurred in Caspase-3, Bax, and Bcl-2 expression between groups, but cellular changes in cortical areas were significantly correlated with protein expression patterns. Cluster analysis of the frequencies and durations of behaviors grouped them as exploratory, learning, preparatory, consumptive, and foraging behaviors. Neonatal inflammatory pain exposure reduced exploratory behaviors in adult males, learning and preparatory behaviors in females, whereas Ketamine ameliorated these long-term effects.

Conclusion

Neuroprotective effects of Ketamine attenuate the impaired cognitive behaviors resulting from pain-induced cell death in the cortical and hippocampal fields of neonatal rats. This cell death was not dependent on the apoptosis associated proteins, but was correlated with glial activation.
Influence of monolayer, spheroid, and tumor growth conditions on chromosome 3 gene expression in tumorigenic epithelial ovarian cancer cell lines
Authors: Cody Neal AL , Zietarska Magdalena , Filali-Mouhim Ali , Provencher Diane M , Mes-Masson Anne-Marie , Tonin Patricia N
Published: August 2008

Background

Expression microarray analyses of epithelial ovarian cancer (EOC) cell lines may be exploited to elucidate genetic and epigenetic events important in this disease. A possible variable is the influence of growth conditions on discerning candidates. The present study examined the influence of growth conditions on the expression of chromosome 3 genes in the tumorigenic EOC cell lines, OV-90, TOV-21G and TOV-112D using Affymetrix GeneChip® HG-U133A expression microarray analysis.

Methods

Chromosome 3 gene expression profiles (n = 1147 probe sets, representing 735 genes) were extracted from U133A expression microarray analyses of the EOC cell lines OV-90, TOV-21G and TOV-112D that were grown as monolayers, spheroids or nude mouse xenografts and monolayers derived from these tumors. Hierarchical cluster analysis was performed to compare chromosome 3 transcriptome patterns of each growth condition. Differentially expressed genes were identified and characterized by two-way comparative analyses of fold-differences in gene expression between monolayer cultures and each of the other growth conditions, and between the maximum and minimum values of expression of all growth conditions for each EOC cell line.

Results

An overall high degree of similarity (> 90%) in gene expression was observed when expression values of alternative growth conditions were compared within each EOC cell line group. Two-way comparative analysis of each EOC cell line grown in an alternative condition relative to the monolayer culture showed that overall less than 15% of probe sets exhibited at least a 3-fold difference in expression profile. Less than 23% of probe sets exhibited greater than 3-fold differences in gene expression in comparisons of the maximum and minimum value of expression of all growth conditions within each EOC cell line group. The majority of these differences were less than 5-fold. There were 17 genes in common which were differentially expressed in all EOC cell lines. However, the patterns of expression of these genes were not necessarily the same for each growth condition when one cell line was compared with another.

Conclusion

The various alternative in vivo and in vitro growth conditions of tumorigenic EOC cell lines appeared to modestly influence the global chromosome 3 transcriptome supporting the notion that the in vitro cell line models are a viable option for testing gene candidates.
Acute myocardial infarction in an 18 year old South Indian girl with familial hypercholesterolemia: a case report
Authors: Kumar Anita A , Shantha Ghanshyam Palamaner Subash , Srinivasan Yadav , Senthil N , Rajkumar K , Paunikar Neeta , Sudhakar MK
Published: August 2008

Familial hypercholesterolemia is a single gene disorder with an autosomal dominant pattern of inheritance. Here we report an 18 year old South Indian girl who presented with myocardial infarction. She had xanthomas and an elevated serum low density lipoprotein cholesterol (LDL-C). Her mother and maternal uncle had died at a young age due to myocardial infarction. Her only sibling, 15 year old younger sister also had xanthomas and an elevated LDL-C. This report is to emphasise the need to clinically recognize xanthomas and its association with elevated LDL-C, premature atherosclerosis and familial inheritance. Early diagnosis and early initiation of treatment will save the affected individual and the other family members.
Continuing trastuzumab beyond disease progression: outcomes analysis in patients with metastatic breast cancer
Authors: Cancello Giuseppe , Montagna Emilia , D'Agostino Diego , Giuliano Mario , Giordano Antonio , Di Lorenzo Giuseppe , Plaitano Monica , De Placido Sabino , De Laurentiis Michele
Published: August 2008

Introduction

We performed a retrospective analysis of HER2-overexpressing metastatic breast cancer patients to describe clinical outcomes of those who, despite progression of the disease (PD), maintained trastuzumab for multiple chemotherapy lines. We also compared survival of these patients with that of those who halted trastuzumab at first PD.

Methods

We identified 101 patients treated between July 2000 and January 2007. Nineteen were still receiving the first-line trastuzumab-based treatment without evidence of PD and were not included in this analysis. Of the remaining 82 patients, 59 retained trastuzumab for one or more additional lines of chemotherapy after PD, according to our institution policy. Twenty-three patients who changed treating institution and stopped trastuzumab at first progression were used as a control group.

Results

For patients retaining trastuzumab, the median follow-up was 39.6 months. Clinical outcomes showed the typical degradation between first and second lines of therapy which we would expect by halting trastuzumab at first progression. Response rates were 35% and 16% and median times to progression were 7.25 and 5.25 months for the first and second lines of trastuzumab therapy, respectively. The median overall survival (OS) rates were 70 months for patients who retained trastuzumab and 56 months for patients who halted the drug (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.51 to 1.18; P = 0.52). If we consider OS from the start of trastuzumab therapy, the figures are 53.9 and 34.8 months, respectively (HR 0.78, 95% CI 0.58 to 1.32; P = 0.2).

Conclusion

A nonstatistically significant trend of improved survival for patients retaining trastuzumab is observed. This is in line with most retrospective analyses and recent randomized data. Retaining trastuzumab after progression is a reasonable option, but further randomized data are warranted to better define its role in comparison with other available options.
Enrichment with anti-cytokeratin alone or combined with anti-EpCAM antibodies significantly increases the sensitivity for circulating tumor cell detection in metastatic breast cancer patients
Authors: Deng Glenn , Herrler Michael , Burgess David , Manna Edward , Krag David , Burke Julian F
Published: August 2008

Introduction

Circulating tumor cells (CTCs) are detectable in most cancer patients and they can meet an existing medical need to monitor cancer patients during a course of treatment and to help determine recurrent disease. CTCs are rarely found in the blood of cancer patients and enrichment is necessary for sensitive CTC detection. Most CTC enrichment technologies are anti-EpCAM antibody based even though CTC identification criteria are cytokeratin positive (CK+), CD45 negative (CD45-) and 4'6-diamidino-2-phenylindole (nuclear stain) positive (DAPI+). However, some tumor cells express low or no EpCAM. Here we present a highly sensitive and reproducible enrichment method that is based on binding to anti-CK alone or a combination of anti-CK and anti-EpCAM antibodies.

Methods

Blood samples from 49 patients with metastatic breast cancer were processed using the CellSearch™ system (Veridex, LLC, Raritan, NJ, USA), in parallel with our CTC assay method. We used anti-CK alone or in combination with anti-EpCAM antibodies for CTC enrichment. Brightfield and fluorescence labeled anti-CK, anti-CD45 and DAPI (nuclear stain) images were used for CTC identification. The Ariol® system (Genetix USA Inc, San Jose, CA, USA) was used for automated cell image capture and analysis of CTCs on glass slides.

Results

Our method has the capability to enrich three types of CTCs including CK+&EpCAM+, CK+&EpCAM-/low, and CK-/low&EpCAM+ cells. In the blind method comparison, our anti-CK antibody enrichment method showed a significantly higher CTC positive rate (49% vs. 29%) and a larger dynamic CTC detected range (1 to 571 vs. 1 to 270) than that of the CellSearch™ system in the total of 49 breast cancer patients. Our method detected 15 to 111% more CTCs than the CellSearch™ method in patients with higher CTC counts (>20 CTCs per 7.5 ml of blood). The three fluorescent and brightfield images from the Ariol® system reduced the number of false-positive CTC events according to the established CTC criteria.

Conclusion

Our data indicate that the tumor-specific intracellular CK marker could be used for efficient CTC enrichment. Enrichment with anti-CK alone or combined with anti-EpCAM antibodies significantly enhances assay sensitivity. The three fluorescent and brightfield superior images with the Ariol® system reduced false-positive CTC events.
Chorionic gonadotropin up-regulates long pentraxin 3 expression in myeloid cells
Authors: Wan Hui , van Helden-Meeuwsen Cornelia G , Garlanda Cecilia , Leijten Lonneke M E , Maina Virginia , Khan Nisar A , Drexhage Hemmo A , Mantovani Alberto , Benner Robbert , Versnel Marjan A
Published: August 2008

Pentraxin 3 (PTX3) is an acute-phase response protein that initiates innate immunity against diverse microorganisms. It is produced in response to proinflammatory stimuli by many cell types including myeloid cells. Increased serum levels of PTX3 are found in pregnancy, a condition characterized by increased serum levels of the pregnancy hormone human chorionic gonadotropin (hCG). As myeloid cells bear the receptor for hCG, we hypothesized that hCG can promote innate immunity by affecting the PTX3 production by myeloid cells. In this paper, we demonstrate that hCG increases PTX3 expression by human monocytes, mouse dendritic cells, and mouse macrophages in vitro. This increased PTX3 expression by hCG is mediated via the protein kinase A signaling pathway. hCG injection in mice also increases the PTX3 serum levels. This serum PTX3 is produced mainly by blood monocytes, which from pregnant women, express more PTX3 compared with nonpregnant controls. The hCG-induced hormones progesterone and estrogen also increase the PTX3 production by human monocytes. In conclusion, hCG increases innate immunity via induction of PTX3 in myeloid cells.
New Standards and Implications for Improving the Quality of Supportive Oncology Practice
Authors: Ferrell Betty , Paice Judith , Koczywas Marianna
Published: August 2008

The purpose of this article is to review current guidelines and national initiatives to improve the quality of supportive oncology care. Review of the literature in this area has documented important advances in supportive oncology. This article focuses on work by the National Consensus Project for Quality Palliative Care and the National Quality Forum. The mandate to improve the quality of care in oncology has been the focus of several national reports, including those by the Institute of Medicine addressing end-of-life care in cancer and cancer survivorship. Patients with cancer face significant needs for support in areas such as pain and symptom management and psychosocial and spiritual support, as well as diverse quality-of-life concerns. These reports recommending changes in practice have been reinforced by clinical practice guidelines developed by the National Consensus Project for Quality Palliative Care and preferred practices defined by the National Quality Forum. This article applies these national mandates and guidelines to the field of supportive care in oncology. Improving the quality of supportive oncology will require commitment by oncology professionals in areas of education, clinical practice, and research.