bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of baseline lung function on the determination of time to bronchiolitis obliterans syndrome
Authors: Burton Christopher M. , Iversen Martin , Carlsen Jørn , Andersen Claus , Mortensen Jann 
Published: September 2008

Long term survival after lung transplantation depends on the development and severity of bronchiolitis obliterans syndrome (BOS).The objective of this study was to identify the relationship between baseline FEV1and transplant procedure type, on the development and progression of BOS grade 0p to 3. All patients receiving a cadaveric lung transplant 1992-2004 were included in the study (n = 389). Exclusion criteria were patients surviving <3 months (n = 39) and missing spirometry measurements (n = 4).There were significant differences between the transplant procedures, heart-lung (HLTx), double-lung (DLTx), and single-lung (SLTx), with respect to recipient age, BMI, and indication for transplantation. Baseline FEV1for HLTx (median 2.9L, quartiles 2.3–4.3L) and DLTx recipients (median 2.9L, quartiles 2.4–3.7L) were significantly larger than for patients undergoing SLTx procedures (median 1.6L, quartiles 1.3–1.9L), p<0.0001, respectively. Survival analyses demonstrated a significant association between baseline FEV1per litre and the development of BOS: grade 0p (HR: 0.59, CI: 0.51–0.68, p<0.0001); grade 1 (HR: 0.60, CI: 0.51–0.70. p<0.0001); grade 2 (HR: 0.62, CI 0.52–0.74, p<0.0001); and grade 3 (HR: 0.73, CI 0.60–0.89, p = 0.002). There was a significant log-log linear relationship between baseline FEV1and time to the development of BOS grades 0p to 3 in all patients developing the respective BOS grade (p<0.0001, respectively).Baseline lung function is an important confounder and should be considered in future risk factor evaluations for the development and progression to BOS.
Monitoring the efficacy of anti-TB therapy by using the QuantiFERON-TB Gold In tube test
Authors: Markova R. , Drenska R. , Todorova Y. , Terzieva V. , Stefanova D. 
Published: September 2008

Monitoring the efficacy of anti-TB therapy is crucial for the better control of the spread of MTB infection, but it is often difficult especially for patients without microbiological confirmation of the disease. IGRAs are novel indirect blood tests for M. tuberculosis infection and a promising marker of mycobacterial burden and disease activity.To describe our experience with the use of the QuantiFERON-TB Gold In tube assay for monitoring of anti-TB therapy in patients with active disease 30 patients with active TB, all HIV-negative and BCG-vaccinated at birth, were studied before and after three and eight months of anti-TB therapy. The whole blood QFT G In tube assay was used to measure the MTB-specific IFN-gamma responses.Before therapy 28/30 patients had positive results in QFT G In tube (QFT) and two – indeterminate. Three months after initiation of treatment all subjects tested were found positive. On month eight a significant decrease of MTB-specific responses was found in all patients but only 17/30 (56.7%) turned negative in QFT. Three of 13 patients with a positive response at the end of month eight, continued to have microbiological isolation and absence of clinical improvement (fig. 1, table 1).On the basis of the results obtained, we concluded that the QFT Gold In tube assay could be used in routine clinical practice for monitoring anti-tuberculosis therapy. Further studies including larger number of patients and longer periods of observation are needed.
Improving inhaler use in COPD and the role of patient preference: FIGURE 1.
Authors: Bateman E. D. 
Published: September 2008

Chronic obstructive pulmonary disease (COPD) is a difficult disease to manage, but recent research focusing on its pathophysiology has provided direction for the development of new treatments and improved management strategies.COPD differs substantially from asthma, both in its pathophysiology and its treatment. Unlike asthma, COPD cannot be fully controlled or “reversed”; it is progressive and responses to anti-inflammatory drugs, including corticosteroids, have been disappointing, suggesting the presence of a unique, persistent form of inflammation. The current main emphasis in the treatment of COPD is therefore to minimise airflow obstruction using regular bronchodilator therapy. Apparently small improvements in traditional measures of airflow obstruction, such as functional residual capacity, may produce significant improvements in other measures, resulting in clinical benefit.Ensuring efficient delivery of bronchodilators is vital to treatment success but has received little attention in guidelines to date. Inhaler technique, adherence rates and levels of satisfaction with therapy are all far from ideal. Improvements in these areas require more detailed consideration of the interactions between the patient, the healthcare provider and the inhaler device, and an examination of how inhaler choices are currently made by both healthcare provider and patient.
Patient needs and medication styles in COPD: FIGURE 1.
Authors: Osman L. M. , Hyland M. E. 
Published: September 2008

Patient self-care in illnesses such as chronic obstructive pulmonary disease (COPD) is influenced by “trade-offs” that patients make between their social and psychological needs, and the “best practice” clinical management of their illness. Patients weigh the benefits of taking medication against the costs, such as symptoms.Personal styles of medication use and decision-making also affect how well COPD patients respond to treatment plans and their acceptance of particular treatments, including inhalers. The large amount of information now available may have made patients more autonomous than before, but the actual locus of control varies widely between patients. Patients seem to take a pragmatic approach when assessing inhaler devices, basing preference on how effective they perceive the device to be. Patients with COPD show loyalty to devices and, in the main, try to comply with instructions given by the healthcare provider.The health path for chronic obstructive pulmonary disease, which describes the course the disease typically takes, is a progressive deterioration. Patients therefore adopt a conservative attitude to their health goals and what they expect to gain from treatment and management plans. An understanding of these influences will help healthcare providers support the patient better and give the appropriate advice at each phase of a patient's health path.
Inhaler treatment options in COPD
Authors: Newman S. P. 
Published: September 2008

A variety of inhaler devices are available for delivering treatments to patients with chronic obstructive pulmonary disease, and new inhalers are currently being developed. Each type of device has advantages and disadvantages, and the methods of preparation and use vary between them. The differences in instructions for use can easily confuse patients and health providers alike, resulting in incorrect use of many inhalers. “Crucial” errors in inhaler technique, whereby no drug is deposited in the lungs, must be avoided. Any type of inhaler can be misused so that little or no drug is deposited in the lungs.It is now increasingly widely recognised that a successful treatment outcome in chronic obstructive pulmonary disease depends as much on the inhaler device as it does on the drug. Inhaler choice in chronic obstructive pulmonary disease should take into account whether the patient is likely to use it correctly, as well as patient preference and the likelihood of adherence to treatment.
In vivomodels of human airway epithelium repair and regeneration
Authors: Coraux C. , Hajj R. , Lesimple P. , Puchelle E. 
Published: September 2008

Despite an efficient defence system, the airway surface epithelium, in permanent contact with the external milieu, is frequently injured by inhaled pollutants, microorganisms and viruses. The response of the airway surface epithelium to an acute injury includes a succession of cellular events varying from the loss of the surface epithelium integrity to partial shedding of the epithelium or even to complete denudation of the basement membrane. The epithelium has then to repair and regenerate to restore its functions. Thein vivostudy of epithelial regeneration in animal models has shown that airway epithelial cells are able to dedifferentiate, spread, migrate over the denuded basement membrane and progressively redifferentiate to reconstitute a functional respiratory epithelium after several weeks.Humanised tracheal xenograft models have been developed in immunodeficient nude and severe combined immunodeficient (SCID) mice in order to mimic the natural regeneration process of the human airway epithelium and to analyse the cellular and molecular events involved during the different steps of airway epithelial reconstitution. These models represent very powerful tools for analysing the modulation of the biological functions of the epithelium during its regeneration. They are also very useful for identifying stem/progenitor cells of the human airway epithelium.A better knowledge of the mechanisms involved in airway epithelium regeneration, as well as the characterisation of the epithelial stem and progenitor cells, may pave the way to regenerative therapeutics, allowing the reconstitution of a functional airway epithelium in numerous respiratory diseases, such as asthma, chronic obstructive pulmonary diseases, cystic fibrosis and bronchiolitis.
Costs of managing asthma as defined by a derived Asthma Control TestTMscore in seven European countries
Authors: Vervloet D. , Williams A. E. , Lloyd A. , Clark T. J. H. 
Published: September 2008

The present authors explored the relationship between asthma control status, as measured by a derived Asthma Control TestTM(ACT) score, and the utilisation and cost of healthcare in Europe.Data were derived from a European survey of asthma patients. Frequency of healthcare resource use was identified from the dataset and per-patient mean cost of asthma management estimated. Drug costs were not available. The ACT score was derived from questions in the survey identical or similar to the items comprising the ACT.An ACT score was derived for 2,268 patients, of whom 48% (1,078) scored <20, suggesting their asthma was not well controlled, with 17% (381) scoring <15, suggesting poorly controlled asthma. The mean per-patient annual cost of asthma management for patients with a derived ACT of <15 was €1,604 (95% confidence interval: €1,219–2,084); for patients with a derived ACT score of 15–19, €512 (€404–660) and for patients with a derived ACT score of ≥20, €232 (€192–286). A higher derived ACT score was associated with significantly lower expenditure on asthma management.Worse asthma control, as measured by the derived Asthma Control TestTMscore was associated with an increased requirement for unscheduled care and with higher cost.
YB-1 promotes microtubule assembly in vitro through interaction with tubulin and microtubules
Authors: Chernov Konstantin G , Mechulam Alain , Popova Nadezhda V , Pastre David , Nadezhdina Elena S , Skabkina Olga V , Shanina Nina A , Vasiliev Victor D , Tarrade Anne , Melki Judith , Joshi Vandana , Baconnais Sonia , Toma Flavio , Ovchinnikov Lev P , Curmi Patrick A 
Published: September 2008

Abstract

Background
YB-1 is a major regulator of gene expression in eukaryotic cells. In addition to its role in transcription, YB-1 plays a key role in translation and stabilization of mRNAs.

Results
We show here that YB-1 interacts with tubulin and microtubules and stimulates microtubule assembly in vitro. High resolution imaging via electron and atomic force microscopy revealed that microtubules assembled in the presence of YB-1 exhibited a normal single wall ultrastructure and indicated that YB-1 most probably coats the outer microtubule wall. Furthermore, we found that YB-1 also promotes the assembly of MAPs-tubulin and subtilisin-treated tubulin. Finally, we demonstrated that tubulin interferes with RNA:YB-1 complexes.

Conclusion
These results suggest that YB-1 may regulate microtubule assembly in vivo and that its interaction with tubulin may contribute to the control of mRNA translation.
Large-scale identification of polymorphic microsatellites using an in silico approach
Authors: Tang Jifeng , Baldwin Samantha J , Jacobs Jeanne ME , van der Linden C Gerard , Voorrips Roeland E , Leunissen Jack AM , van Eck Herman , Vosman Ben 
Published: September 2008

AbstractBackgroundSimple Sequence Repeat (SSR) or microsatellite markers are valuable for genetic research. Experimental methods to develop SSR markers are laborious, time consuming and expensive.In silicoapproaches have become a practicable and relatively inexpensive alternative during the last decade, although testing putative SSR markers still is time consuming and expensive. In many species only a relatively small percentage of SSR markers turn out to be polymorphic. This is particularly true for markers derived from expressed sequence tags (ESTs). In EST databases a large redundancy of sequences is present, which may contain information on length-polymorphisms in the SSR they contain, and whether they have been derived from heterozygotes or from different genotypes. Up to now, although a number of programs have been developed to identify SSRs in EST sequences, no software can detect putatively polymorphic SSRs.ResultsWe have developed PolySSR, a new pipeline to identify polymorphic SSRs rather than just SSRs. Sequence information is obtained from public EST databases derived from heterozygous individuals and/or at least two different genotypes. The pipeline includes PCR-primer design for the putatively polymorphic SSR markers, taking into account Single Nucleotide Polymorphisms (SNPs) in the flanking regions, thereby improving the success rate of the potential markers. A large number of polymorphic SSRs were identified using publicly available EST sequences of potato, tomato, rice,Arabidopsis,Brassicaand chicken.The SSRs obtained were divided into long and short based on the number of times the motif was repeated. Surprisingly, the frequency of polymorphic SSRs was much higher in the short SSRs.ConclusionPolySSR is a very effective tool to identify polymorphic SSRs. Using PolySSR, several hundred putative markers were developed and stored in a searchable database. Validation experiments showed that almost all markers that were indicated as putatively polymorphic by polySSR were indeed polymorphic. This greatly improves the efficiency of marker development, especially in species where there are low levels of polymorphism, like tomato. When combined with the new sequencing technologies PolySSR will have a big impact on the development of polymorphic SSRs in any species.PolySSR and the polymorphic SSR marker database are available fromhttp://www.bioinformatics.nl/tools/polyssr/.
Functional analyses reveal an important role for tyrosine residues in the staphylococcal multidrug efflux protein QacA
Authors: Wu Jingqin , Hassan Karl A , Skurray Ronald A , Brown Melissa H 
Published: September 2008

Abstract

Background
The staphylococcal QacA multidrug efflux protein confers resistance to an exceptional number of structurally unrelated antimicrobial compounds. Aromatic amino acid residues have been shown to be highly important for the transport function of several multidrug transporters and are intimately involved in multidrug binding. This study investigated the structural and functional importance of the seven tyrosine residues in QacA by examining the phenotypic effect of incorporating conservative (aromatic) and non-conservative (non-aromatic) substitutions for these residues.

Results
Determination of the resistance profiles and analysis of drug transport assays revealed that non-conservative substitutions for most tyrosine residues influenced the QacA drug recognition spectrum. However, an aromatic residue at three tyrosine positions, 63, 410 and 429, was of importance for QacA-mediated transport and resistance to the majority of substrates tested.

Conclusion
A tyrosine or phenylalanine residue at amino acid positions corresponding to 63 of QacA in related drug efflux proteins is found to be highly conserved. Therefore, an aromatic side chain at this position is likely to partake in a function common to these drug transporters, such as proton translocation or essential intramolecular contacts, whereas aromatic residues at the non-conserved 410 and 429 positions are expected to mediate a QacA-specific function, possibly forming or stabilising part of the QacA drug binding region.
Cinnamaldehyde and cinnamaldehyde derivatives reduce virulence in Vibrio spp. by decreasing the DNA-binding activity of the quorum sensing response regulator LuxR
Authors: Brackman Gilles , Defoirdt Tom , Miyamoto Carol , Bossier Peter , Van Calenbergh Serge , Nelis Hans , Coenye Tom 
Published: September 2008

AbstractBackgroundTo date, only few compounds targeting the AI-2 based quorum sensing (QS) system are known. In the present study, we screened cinnamaldehyde and substituted cinnamaldehydes for their ability to interfere with AI-2 based QS. The mechanism of QS inhibition was elucidated by measuring the effect on bioluminescence in severalVibrio harveyimutants. We also studiedin vitrothe ability of these compounds to interfere with biofilm formation, stress response and virulence ofVibriospp. The compounds were also evaluated in anin vivoassay measuring the reduction ofVibrio harveyivirulence towardsArtemiashrimp.ResultsOur results indicate that cinnamaldehyde and several substituted derivatives interfere with AI-2 based QS without inhibiting bacterial growth. The active compounds neither interfered with the bioluminescence system as such, nor with the production of AI-2. Study of the effect in various mutants suggested that the target protein is LuxR. Mobility shift assays revealed a decreased DNA-binding ability of LuxR. The compounds were further shown to (i) inhibit biofilm formation in severalVibriospp., (ii) result in a reduced ability to survive starvation and antibiotic treatment, (iii) reduce pigment and protease production inVibrio anguillarumand (iv) protect gnotobioticArtemiashrimp against virulentVibrio harveyiBB120.ConclusionCinnamaldehyde and cinnamaldehyde derivatives interfere with AI-2 based QS in variousVibriospp. by decreasing the DNA-binding ability of LuxR. The use of these compounds resulted in several marked phenotypic changes, including reduced virulence and increased susceptibility to stress. Since inhibitors of AI-2 based quorum sensing are rare, and considering the role of AI-2 in several processes these compounds may be useful leads towards antipathogenic drugs.
Comparative analysis of emmtype pattern of Group A Streptococcus throat and skin isolates from India and their association with closely related SIC, a streptococcal virulence factor
Authors: Sagar Vivek , Kumar Rajesh , Ganguly Nirmal K , Chakraborti Anuradha 
Published: September 2008

Abstract

Background
Group A streptococcus (GAS) causes a wide variety of life threatening diseases in humans and the incidence of such infections is high in developing countries like India. Although distribution of emm types of GAS in India has been described, there is a lack of data describing either the comparative distribution of emm types in throat versus skin isolates, or the distribution of certain virulence factors amongst these isolates. Therefore in the present study we have monitored the emm type pattern of Group A streptococcus throat and skin isolates from India. Additionally, the association of these isolates with closely related sic (crs), a multifunctional compliment binding virulence factor, was also explored.

Results
Of the 94 (46 throat and 48 skin) isolates analyzed, 37 emm types were identified. The most frequently observed emm types were emm49 (8.5%) and emm112 (7.5%) followed by 6.5% each of emm1-2, emm75, emm77, and emm81. Out of 37 emm types, 27 have been previously reported and rest were isolated for the first time in the Indian Community. The predominant emm types of throat (emm49 and emm75) samples were different from those of skin (emm44, emm81 and emm112) samples. After screening all the 94 isolates, the crs gene was found in six emm1-2 (crs1-2) isolates, which was confirmed by DNA sequencing and expression analysis. Despite the polymorphic nature of crs, no intravariation was observed within crs1-2. However, insertions and deletions of highly variable sizes were noticed in comparison to CRS isolated from other emm types (emm1.0, emm57). CRS1-2 showed maximum homology with CRS57, but the genomic location of crs1-2 was found to be the same as that of sic1.0. Further, among crs positive isolates, speA was only present in skin samples thus suggesting possible role of speA in tissue tropism.

Conclusion
Despite the diversity in emm type pattern of throat and skin isolates, no significant association between emm type and source of isolation was observed. The finding that the crs gene is highly conserved even in two different variants of emm1-2 GAS (speA +ve and -ve) suggests a single allele of crs may be prevalent in the highly diverse throat and skin isolates of GAS in India.
Effects of the N-methyl-D-Aspartate receptor antagonist dextromethorphan on vibrotactile adaptation
Authors: Folger Stephen E , Tannan Vinay , Zhang Zheng , Holden Jameson K , Tommerdahl Mark 
Published: September 2008

Abstract

Background
Previous reports have demonstrated that short durations of vibrotactile stimuli (less than or equal to 2 sec) effectively and consistently modify both the perceptual response in humans as well as the neurophysiological response in somatosensory cortex. The change in cortical response with adaptation has been well established by a number of studies, and other reports have extended those findings in determining that both GABA- and NMDAR-mediated neurotransmission play a significant role in the dynamic response of somatosensory cortical neurons. In this study, we evaluated the impact that dextromethorphan (DXM), an NMDAR antagonist, had on two distinct vibrotactile adaptation tasks.

Results
All subjects, both those that ingested 60 mg DXM and those that ingested placebo, were evaluated for their amplitude discriminative capacity between two simultaneously delivered vibrotactile stimuli both with and without 3 conditions of pre-exposure to adapting stimulation. The results demonstrated that the perceptual metrics of subjects who ingested 60 mg DXM were significantly altered from that of controls when the amplitude discrimination task followed one of the conditions of adapting stimulation. Without the condition of pre-exposure to an adapting stimulus (or stimuli), there was little difference between the observations obtained from the subjects that ingested DXM and controls. Peak impact on subject response occurred at 60 min post-ingestion, whereas the scores of controls who ingested placebo were not impacted.

Conclusion
The results – that DXM blocks vibrotactile adaptation – is consistent with the suggestion that NMDAR-mediated neurotransmission plays a significant role in the perceptual adaptive response. This finding is also consistent with neurophysiological findings that report observations of the effects of NMDAR block on the SI cortical response to repetitive vibrotactile stimulation.