bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment effects of sleep apnoea: where are we now?
Authors: Buyse B.
Published: September 2008

The present article summarises some of the topics of discussion held during one of the workshops in preparation for the 7thInternational Symposium of the Katholieke Universiteit Leuven on “Respiratory somnology: a clinical update; March 2006”. Participants discussed the effectiveness of treatment in obstructive sleep apnoea/hypopnoea syndrome (OSAHS).

Of the topics discussed, the following are considered in the present article. 1) Sleepiness and attention deficit, as well as higher cognitive/executive defects in OSAHS, and the closely related clinical dilemma of “how to deal with the car-driving-ability problem in OSAHS”. 2) Continuous positive airway pressure (CPAP) in post-stroke patients. The most important data discussed during the workshop for 1) and 2) are presented in the present article. 3) The effects of CPAP on metabolic outcome. One metabolic dysfunction of OSAHS is the change in leptin and ghrelin levels, which represent the “yin and yang” of an appetite regulatoion system that has developed to inform the brain about the current energy balance state. Data on the impact of sleep loss, either behavioural or OSAHS-related, on this neuroendocrine regulation of appetite are also presented.

The participants ended the workshop with a discussion session on the results of more “controversial” treatment strategies for obstructive sleep apnoea/hypopnoea syndrome, such as cardiac pacing, hyoid bone expansion (a preliminary surgical technique), drug treatment for obstructive sleep apnoea/hypopnoea syndrome, female hormone replacement therapy and the role of stimulants for refractory sleepiness in already treated obstructive sleep apnoea/hypopnoea syndrome patients.
Treatment of obstructive and central sleep apnoea in heart failure: practical options: Table 1—
Authors: Javaheri S.
Published: September 2008

Sleep apnoea, both central and obstructive disordered breathing, commonly occurs in patients with heart failure.

Obstructive sleep apnoea occurs both in systolic and diastolic heart failure and is best treated with nasal positive airway pressure devices.

Central sleep apnoea occurs primarily in systolic heart failure and therapeutic options are evolving.

Optimal therapy of systolic heart failure, nocturnal use of supplemental oxygen, theophylline, acetazolamide and positive airway pressure devices have been shown to improve central sleep apnoea. Among these therapeutic modalities only continuous positive airway pressure has been studied in a long-term trials; unfortunately, it failed to improve survival.
Metabolic disturbances in patients with obstructive sleep apnoea syndrome
Authors: Harsch I. A.
Published: September 2008

The metabolic disturbances in patients with obstructive sleep apnoea syndrome (OSAS) include insulin resistance and elevated levels of pro-inflammatory cytokines and vascular adhesion molecules, as well as an elevation of hormones derived from the adipose tissue as leptin. These phenomena might, in part, be an explanation for the excess morbidity and mortality of OSAS patients concerning cardiovascular disease.

Several of these factors have been described as being independently associated with OSAS and not only related to its comorbidities, including obesity.

A promising approach to studying the metabolic phenomena in these OSAS patients would be to monitor patients before and during the course of continuous positive airway pressure therapy, as nocturnal sleep disturbances are treatable and may revert the impact of OSAS on the metabolic phenomena; however, patients do frequently (and unfortunately) maintain their body weight.

Although not confirmed by all investigations, a tendency towards an improvement in some of the above-mentioned metabolic parameters has been reported in several studies in obstructive sleep apnoea syndrome patients and may be reflected by the decreased occurrence of new cardiovascular events, the reduction of systolic blood pressure and the improvement of left ventricular systolic function.
Analysis of emergency helpline support for home ventilator dependent patients: risk management and workload
Authors: Chatwin M. , Heather S. , Hanak A. , Polkey M. I. , Wilson B. , Simonds A. K.
Published: September 2008

From a total of 1211 adult & paediatric patients receiving home ventilation (HV) supervised by Royal Brompton Hospital between 1/1/06 and 30/6/06 the respiratory support team received an average of 528 daytime calls/month and 14/month out of hours calls to a telephone helpline.

Diagnoses included: neuromuscular disease, chest wall disease, COPD, obesity hypoventilation and non-COPD lung disease. 99% received non-invasive ventilation, 1% tracheostomy ventilation. 149 required 2 ventilators for near 24 hour ventilator dependency, the remainder were classified as 1 (17%) 2 (33%) & 3 (50%) night dependency as were able to breathe spontaneously for this period. 50% used bilevel positive pressure ventilators, 48% inspiratory pressure ventilators and 2% volume ventilators. In 188 calls a home visit was carried out because of ventilator or associated equipment-related problems. Despite regular equipment servicing programme, in 188 patients there was a technical problem with the equipment which was solved in the patient's home in 64% or required replacement / parts in 22%. Of the 25 calls in which no fault was found, 13 patients were unwell at home or required hospital admission, 2 patients died within 1 month of identification of no fault. No patient was admitted as a result of technical failure of equipment.

Conclusion: There is a significant workload associated with supporting HV patients. Patients / carers all received standard competency training before discharge but other calls may be reduced by a more flexible problem-solving approach. Importantly, reports in which no technical fault is found may indicate deteriorating health in the patient and require close follow-up.
Activation of eosinophilsviaToll-like receptor (TLR)3, TLR7 and TLR9: link between viral infection and asthma?
Authors: Månsson Anne , Cardell Lars Olaf
Published: September 2008

Asthma is disease characterized by a massive accumulation of eosinophils that release an array of tissue-damaging mediators. Respiratory viral infections are thought to be a leading cause of exacerbations of asthma. One possible explanation might be a direct activation of viral components through Toll-like receptors (TLRs), a receptor family comprising 10 different pathogen-recognizing members (TLR1-TLR10). The virus-recognizing TLRs are TLR3, TLR7/8 and TLR9, which respond to viral dsRNA, ssRNA and CpG-DNA. The present study aimed to investigate the expression of these TLRs and their functions in human eosinophils.

Eosinophils were isolated from peripheral blood using magnetic beads (purity >97%). Cells were incubated with or without poly(I:C), R-837 or CpG alone, the synthetic ligands of TLR3, TLR7 and TLR9, respectively, or combined with IL-4 or histamine. Flow cytometry, and ELISA were used to analyze expression of TLRs and various surface markers, viability and secretion of inflammatory mediators.

Eosinophils expressed proteins for TLR3, TLR7 and TLR9. Poly(I:C), R-837 and CpG prolonged survival, up-regulated expression of the adhesion molecule CD11b and increased secretion of IL-8 compared to unstimulated controls. These effects were affected by the presence of IL-4 and histamine.

This study shows that several viral products directly activate eosinophils through their TLRs. Since eosinophils are central in asthma, the TLR system may be an important mechanism of eosinophil activation linking viral infections with exacerbations. Consequently, this system represents a future clinical target for the resolution of asthmatic disease.
Effects of pneumococcal vaccine in patients with chronic respiratory disease
Authors: Watanuki Yuji , Miyazawa N. , Kudo M. , Inoue S. , Goto H. , Takahashi H. , Kaneko T. , Ishigatsubo Y.
Published: September 2008

In developed countries, it is very difficult to demonstrate the effectiveness of pneumococcal vaccines because the incidence of pneumococcal pneumonia is very low.

Vaccination against pneumococci infection was advised for 1378 outpatients, over 60 years of age, with chronic respiratory disease for more than one year. Of these patients, those who responded affirmatively to the advice were vaccinated against pneumococci between August and November 2002. The effectiveness of vaccination was evaluated by means of a 2-year cohort-study, comparing the vaccinated group (647) with the non-vaccinated group (731). The variables analyzed were the frequency of onset of bacterial respiratory infection, hospitalization due to bacterial respiratory infection and onset of pneumococcal respiratory infection.

The incidence of bacterial respiratory infection and the incidence of pneumococcal respiratory infection to have decreased in the following 2 years (17.4%, 0.9%), as compared to the previous year (25.9%, 3.1%), in the vaccinated group. Conversely, the frequency was higher in the following 2 years (14.4%, 0.9%) as compared to the previous year (14.2%, 0.4%) in the non-vaccinated group. This inter-group difference was statistically significant. Simultaneous vaccination against pneumococci and influenza virus also resulted in a significant reduction in the incidence of bacterial respiratory infection. No decrease was observed in the frequency of hospitalization.

These results indicate that pneumococcal vaccine is useful for elderly patients with chronic respiratory disease and that its efficacy may be enhanced by simultaneous vaccination against influenza.
Managing asthma patients: which outcomes matter?
Authors: Greening A. P. , Stempel D. , Bateman E. D. , Virchow J. C.
Published: September 2008

Within the respiratory specialist community, there is growing recognition that classification of asthma based on severity of symptoms alone may not accurately reflect the clinical status of a patient. It follows, therefore, that treatment decisions based on this classification can lead to suboptimal management of asthma.

The concept of assessing patients by their level of asthma control is gaining wide acceptance and is a major component of the new 2006 Global Initiative for Asthma guidelines. Questions remain, however, on how best to achieve and maintain asthma control.

Randomised controlled trials have shown that very good asthma control is achievable in the majority of patients. There is a need for a tool to accurately assess a patient's level of control in the clinical setting if such results are to be replicated in practice.

A symposium at the European Respiratory Society Annual Congress in 2006 discussed the important issues that are currently facing asthma clinicians. The current article summarises the main points arising from that symposium.
Prevention of pulmonary vascular and myocardial remodeling by the combined tyrosine and serine-/threonine kinase inhibitor, sorafenib, in pulmonary hypertension and right heart failure
Authors: Klein M. , Schermuly R. T. , Ellinghaus P. , Milting H. , Riedl B. , Ghofrani H. A. , Grimminger F. , Schäfer S.
Published: September 2008

Inhibition of tyrosine kinases can reverse pulmonary hypertension but little is known about the role of serine-/threonine kinases in vascular and myocardial remodeling. We investigated the effects of sorafenib, an inhibitor of the tyrosine kinases VEGFR, PDGFR and c-kit as well as the serine-/threonine kinase Raf-1, in pulmonary hypertension and right ventricular (RV) pressure overload.

In monocrotaline treated rats, sorafenib (10 mg·kg−1·d−1p.o.) reduced pulmonary arterial pressure, pulmonary artery muscularization and RV hypertrophy, and improved systemic hemodynamics (table 1). Sorafenib prevented phosphorylation of Raf-1 and suppressed activation of downstream signaling pathways (Erk 1/2).

After pulmonary banding, sorafenib, but not the PDGFR/c-KIT/ABL-inhibitor imatinib reduced RV mass and RV filling pressure significantly. Congruent with these results, sorafenib only prevented ERK phosphorylation and vasopressin induced hypertrophy of the cardiomyocyte cell line H9c2 dose dependently (IC50 = 300 nM).

Combined inhibition of tyrosine and serine-/threonine kinases by sorafenib prevents vascular and cardiac remodeling in pulmonary hypertension, which is partly mediated via inhibition of the Raf kinase pathway.
The Oxford Transport Strategy: impact of a traffic intervention on PEF and wheeze among children
Authors: MacNeill S. J. , Goddard F. , Pitman R. , Tharme S. , Cullinan P.
Published: September 2008

The Oxford Transport Strategy (OTS) was a major traffic intervention implemented in June 1999. It involved a wide range of permanent changes focused primarily on the city centre of Oxford (England).

We aimed to assess the impact of OTS on peak expiratory flow (PEF) and respiratory symptoms among city schoolchildren.

Between 1998 and 2000, 1389 children aged 6–10 years were visited 2–3 times a year for 5-day periods. On each day of each visit, we measured their PEF and enquired about respiratory symptoms including wheeze (n = 19260 child-days of data). Exposure to traffic pre and post-OTS was estimated by the change in modelled traffic on the street nearest the home.

Pre-OTS traffic levels were relatively low compared to other major cities, but post-OTS changes in children's exposure varied considerably; from a drop of 11184 to an increase of 9240 vehicles/24hrs. Adjusted regression analyses showed a statistically significant improvement in PEF (beta = 5.71 L·min−1, 95% CI (3.28, 8.18)) and wheeze (OR = 0.80, 95% CI (0.69, 0.92)) post-OTS. The impact of OTS on PEF was greater among children living near roads where traffic decreased compared to those living where there had been an increase. This association was only found among children currently receiving treatment for asthma and those in socio-economic classes III–V.

These results suggest that even in cities with relatively low traffic levels interventions can result in improvements in the respiratory health of children. These benefits may be especially pertinent to children with pre-existing respiratory problems and those from less affluent socio-economic backgrounds.
The Leuven experience with a dichotomy in Bronchiolitis Obliterans Syndrome (BOS) after lung transplantation revealed by azithromycin
Authors: Vanaudenaerde Bart , Vos Robin , Geudens Nele , Van Raemdonck Dirk , Dupont Lieven , Verleden Geert
Published: September 2008

BOS is the most important cause of late mortality after LTx. Until 5 years ago, the prevalence was around 30% and 50%, 3 and 5 years after LTx. Introduction of azithromycin (AZI) improved the FEV1in 40% of BOS patients. AZI treatment may explain why in our center, the BOS prevalence at 3 years has decreased from 30% to 15% compared to the ISHLT registry. Opposed to the current belief about BOS, we hypothesize a dichotomy within BOS: Neutrophilic Reversible Allograft Dysfunction (NRAD) and fibropoliferative BOS (fBOS; table 1). This dichotomy is based on the discrepancy in AZI response and observations within our center consisting of clinical, biochemical and cellular (BAL) analysis.

NRAD makes a re-evaluation of the BOS definition (irreversible FEV1decline, neutrophilic inflammation, fibroproliferation) indispensable. As it is reversible, NRAD should be excluded from BOS and accepted as innate (non-specific) inflammation and as an important risk factor for the development of BOS. So after exclusion of other complications such as acute rejection, infection, gastro-oesophageal reflux and after a trial with AZI, BOS will remain what it is now (the fBOS). This implements a re-evaluation of the neutrophilic inflammation, as it is a prerequisite for AZI responsiveness. BOS can then histologically be characterized as pure inactive OB, which is hardly responsive to any treatment.
Impact of neutrophil function on outcomes of community-acquired pneumonia in patients with cancer
Authors: Aliberti Stefano , Amir Asad , Peyrani Paula , Myers John A. , Cirino Maria , Saporiti Matteo , Blasi Francesco , Ramirez Julio A.
Published: September 2008

Some literature suggests that outcomes of CAP in patients with solid tumor without neutropenia may be better than in cancer patients with neutropenia. In order to investigate the role of neutrophils in this population, we retrospectively analyzed consecutive patients with CAP admitted to 3 tertiary care hospitals from 01/2001 through 12/2005. HIV patients were excluded. A total of 993 patients were classified as follows: Group 1: no active cancer; Group 2: solid cancer without neutropenia; Group 3: solid cancer without neutropenia or hematologic malignancy. Age, Pneumonia Severity Index (PSI), overall mortality, time to reach clinical stability (TCS) and length of stay in hospital (LOS) are summarized in the table. No significant differences were found for any of the outcomes between group 2 and 3. Our results suggest that physicians should aggressively manage cancer patients with CAP, regardless of the neutrophil count.
Impact of viruses on airway diseases
Authors: Johnston S. L.
Published: September 2008

There is strong epidemiological evidence that respiratory viral infections are associated with 80–85% of asthma exacerbations in children. There is less evidence in adults, but the available data suggest viruses are associated with around two-thirds to three-quarters of exacerbations in adults. These associations include severe exacerbations requiring hospitalisation. The most common viruses detected in these studies were rhinoviruses, accounting for two-thirds of viruses detected.

Asthmatics have increased susceptibility to respiratory virus infection and have recently been shown to have profoundly defective interferon-β responses to virus infection, resulting in increased virus replication.

Atypical bacterial infections are also associated with chronic asthma and asthma exacerbations and a recent study indicates antibiotic therapy active against atypical bacteria is effective in treatment of exacerbations. Recent data also indicates asthmatics are at increased risk of invasive pneumococcal disease, suggesting they may also have impaired antibacterial immunity.

Research is urgently required to determine whether augmenting anti-infective immunity is beneficial in the treatment/prevention of asthma exacerbations. More recent data also implicates viruses in the majority of exacerbations of chronic obstructive pulmonary disease. Studies are also required investigating anti-infective host defence in chronic obstructive pulmonary disease.
Modulation of airway inflammation to prevent exacerbations of COPD
Authors: Solèr M.
Published: September 2008

Exacerbations of chronic obstructive pulmonary disease (COPD) are periods in the chronic course of this disease with symptoms of intensified inflammation, induced in part by infections but also by noninfectious irritating mechanisms. Although these exacerbations seem to be linked to accelerated long-term disease progression and impaired quality of life, there are only limited preventive measures available, apart from smoking cessation.

This article compares the effectiveness of different pharmacological treatments for the prevention of COPD exacerbations, including the oral bacterial lysate OM-85.

Given the differences in the mechanism of action of the treatments discussed, this opens some hope for additive or potentiating effects with combined treatments, which will have to be studied in future controlled trials.
Effective communication with the patient: FIGURE 1.
Authors: Booker R.
Published: September 2008

The chronic and slowly progressive nature of chronic obstructive pulmonary disease (COPD) can create difficulties in effective communication between healthcare provider and patient. Such barriers, which include the personal beliefs of both caregiver and patient, need to be understood and addressed if the aims of the consultation are to be met.

Patients with COPD may feel guilty, depressed and angry about their condition. Many patients with COPD are elderly and/or from lower socio-economic groups, both of which pose challenges to the caregiver, as does the stigma the disease carries, which stems from its strong link with smoking.

Humanity, respect and people orientation are vital to good communication with COPD patients. Physicians and nurses should try to avoid patient misunderstanding and uncertainty, involve the patient in decision-making and achieve a shared understanding (concordance), as well as encourage the patient to accept responsibility for the actions agreed. This should improve management decisions made by healthcare professionals and ensure a more satisfied patient. Greater patient satisfaction may improve concordance and so bring about better patient outcomes.
Patient adherence with COPD therapy
Authors: Rand C. S.
Published: September 2008

Although there are very few published studies on adherence to treatment regimens in chronic obstructive pulmonary disease (COPD), the evidence that exists suggests that, as with asthma therapy, adherence is poor.

Patient beliefs about COPD, as well as their motivation and expectations about the likelihood of success of medical interventions, can influence adherence rates. Other critical factors include the patient's understanding of their illness and therapy, and the complexity of the prescribed treatment regimen. Incorrect inhaler technique is also a common failing.

When prescribing in primary or specialist care, healthcare professionals should address adherence as a vital part of the patient consultation. Improved patient education may also increase adherence rates.
Patient preference for and satisfaction with inhaler devices
Authors: Anderson P.
Published: September 2008

Preference for and satisfaction with inhaler devices may be associated with improved clinical outcomes, but this has not been proven to date.

A screened Medline search for papers on preference for inhaler devices produced 29 studies on a variety of devices, with Advair Diskus® and TurbuhalerTMfeaturing prominently. Of the 23 studies sponsored by the pharmaceutical industry, the sponsor's device was preferred in 19. Interpretation of results was made more difficult because only two studies used robust instruments for measuring preference and satisfaction. Patients with unstable disease or who were unable to use inhalers were usually excluded, and the extent of instruction and coaching given in the studies was greater than that seen in everyday practice. Studies found no significant differences in clinical outcomes between devices (where measured).

Although inhaler preference is a valid patient-reported outcome deserving of scientific study, assessment and reporting of preference outcomes should follow the same regulatory standards as other patient-reported outcomes.
Current perspectives in epithelial cell injury and repair: consequences for epithelial functions
Authors: Lutter R. , Spiteri M.
Published: September 2008

Epithelial cells lining the airways and the respiratory compartment may, and certainly when exposed to an inflammatory milieu, display an altered functioning, which could contribute to pathophysiology of inflammatory lung/airway disease. In the present review paper, several issues that were discussed at an earlier European Respiratory Society Research Seminar on conditions that affect epithelial functioning have been recapitulated and updated. These and future studies should improve understanding of epithelial functioning and may aid recovery from disease.
Matrix proteoglycans as effector molecules for epithelial cell function
Authors: Frevert C. W. , Sannes P. L.
Published: September 2008

Matrix proteoglycans are complex molecules composed of a core protein and glycosaminoglycan side chains. Once thought to be the molecular glue providing structural support and imparting biomechanical properties to lung tissue, it is now apparent that proteoglycans are important biological modifiers which regulate processes such as lung development, homeostasis, inflammation and wound healing. The diverse roles of proteoglycans in the extracellular matrix suggest that these molecules play a critical role in normal and diseased lungs. This short article will discuss the role extracellular matrix proteoglycans play in regulating epithelial cell function in the lungs.
Asthma management: important issues
Authors: Barnes P. , Virchow J. C. , Sanchis J. , Welte T. , Pedersen S.
Published: September 2008

Although most attention has been focused on the drugs used to control asthma, it is increasingly recognised that effective delivery of these drugs to the lungs is just as important. The most effective drugs, β2-agonists and corticosteroids, are given by inhalation so there has been a search for more efficient inhaler devices that are easier for patients to use. A symposium at the European Respiratory Society Annual Meeting in 2005 discussed some of the important issues in inhaler therapy in adults and children. This article summarises the major points of discussion that arose out of this symposium. New more effective inhaler devices are now becoming available and are likely to have an important impact on asthma management.
Cost of scheduled and unscheduled asthma management in seven European Union countries
Authors: Williams A. E. , Lloyd A. C. , Watson L. , Rabe K. F.
Published: September 2008

Frequent need for emergency healthcare indicates poor asthma control and consumes resources that might be better spent on improved management. This study estimated the cost of scheduled and unscheduled healthcare for asthma in seven European Union (EU) countries.

The occurrence of asthma-related healthcare resource use and asthma symptom severity were identified from a telephone sample of people with asthma in France, Germany, Italy, the Netherlands, Spain, Sweden and the UK. Healthcare resource use was multiplied by country-specific unit costs to estimate per patient annual expenditure. Patients were divided into four groups according to asthma symptom severity: mild intermittent symptoms, mild persistent symptoms, moderate persistent symptoms and severe persistent symptoms. Cost was divided between scheduled and unscheduled care. Drug cost was not evaluable.

The study included 2,803 patients, of whom 1,695 (60%) reported mild symptoms and 2,050 (73%) were aged ≥16 yrs. The average annual per patient cost was €789 for patients aged 0–4 yrs, €463 for patients aged 5–15 yrs and €566 for adults. Unscheduled care accounted for 47% of total cost in infants, 45% in children and 56% in adults.

Around half of expenditure on asthma management was found to be due to unscheduled care regardless of the severity of patient symptoms.
The Mouse Limb Anatomy Atlas: An interactive 3D tool for studying embryonic limb patterning
Authors: DeLaurier April , Burton Nicholas , Bennett Michael , Baldock Richard , Davidson Duncan , Mohun Timothy J , Logan Malcolm PO
Published: September 2008

Background

The developing mouse limb is widely used as a model system for studying tissue patterning. Despite this, few references are available that can be used for the correct identification of developing limb structures, such as muscles and tendons. Existing textual references consist of two-dimensional (2D) illustrations of the adult rat or mouse limb that can be difficult to apply when attempting to describe the complex three-dimensional (3D) relationship between tissues.

Results

To improve the resources available in the mouse model, we have generated a free, web-based, interactive reference of limb muscle, tendon, and skeletal structures at embryonic day (E) 14.5 http://www.nimr.mrc.ac.uk/3dlimb/. The Atlas was generated using mouse forelimb and hindlimb specimens stained using immunohistochemistry to detect muscle and tendon. Limbs were scanned using Optical Projection Tomography (OPT), reconstructed to make 3D models and annotated using computer-assisted segmentation tools in Amira 3D Visualisation software. The annotated dataset is visualised using Java, JAtlasView software. Users click on the names of structures and view their shape, position and relationship with other structures within the 3D model and also in 2D virtual sections.

Conclusion

The Mouse Limb Anatomy Atlas provides a novel and valuable tool for researchers studying limb development and can be applied to a range of research areas, including the identification of abnormal limb patterning in transgenic lines and studies of models of congenital limb abnormalities. By using the Atlas for "virtual" dissection, this resource offers an alternative to animal dissection. The techniques we have developed and employed are also applicable to many other model systems and anatomical structures.
Phylogenetic reconstruction from transpositions
Authors: Yue Feng , Zhang Meng , Tang Jijun
Published: September 2008

Background

Because of the advent of high-throughput sequencing and the consequent reduction in the cost of sequencing, many organisms have been completely sequenced and most of their genes identified. It thus has become possible to represent whole genomes as ordered lists of gene identifiers and to study the rearrangement of these entities through computational means. As a result, genome rearrangement data has attracted increasing attentions from both biologists and computer scientists as a new type of data for phylogenetic analysis. The main events of genome rearrangements include inversions, transpositions and transversions. To date, GRAPPA and MGR are the most accurate methods for rearrangement phylogeny, both assuming inversion as the only event. However, due to the complexity of computing transposition distance, it is very difficult to analyze datasets when transpositions are dominant.

Results

We extend GRAPPA to handle transpositions. The new method is named GRAPPA-TP, with two major extensions: a heuristic method to estimate transposition distance, and a new transposition median solver for three genomes. Although GRAPPA-TP uses a greedy approach to compute the transposition distance, it is very accurate when genomes are relatively close. The new GRAPPA-TP is available from http://phylo.cse.sc.edu/.

Conclusion

Our extensive testing using simulated datasets shows that GRAPPA-TP is very accurate in terms of ancestor genome inference and phylogenetic reconstruction. Simulation results also suggest that model match is critical in genome rearrangement analysis: it is not accurate to simulate transpositions with other events including inversions.
MeDor: a metaserver for predicting protein disorder
Authors: Lieutaud Philippe , Canard Bruno , Longhi Sonia
Published: September 2008

Background

We have previously shown that using multiple prediction methods improves the accuracy of disorder predictions. It is, however, a time-consuming procedure, since individual outputs of multiple predictions have to be retrieved, compared to each other and a comprehensive view of the results can only be obtained through a manual, fastidious, non-automated procedure. We herein describe a new web metaserver, MeDor, which allows fast, simultaneous analysis of a query sequence by multiple predictors and provides a graphical interface with a unified view of the outputs.

Results

MeDor was developed in Java and is freely available and downloadable at: http://www.vazymolo.org/MeDor/index.html. Presently, MeDor provides a HCA plot and runs a secondary structure prediction, a prediction of signal peptides and transmembrane regions and a set of disorder predictions. MeDor also enables the user to customize the output and to retrieve the sequence of specific regions of interest.

Conclusion

As MeDor outputs can be printed, saved, commented and modified further on, this offers a dynamic support for the analysis of protein sequences that is instrumental for delineating domains amenable to structural and functional studies.
Short Linear Motifs recognized by SH2, SH3 and Ser/Thr Kinase domains are conserved in disordered protein regions
Authors: Ren Siyuan , Uversky Vladimir N , Chen Zhengjun , Dunker A Keith , Obradovic Zoran
Published: September 2008

Background

Protein interactions are essential for most cellular functions. Interactions mediated by domains that appear in a large number of proteins are of particular interest since they are expected to have an impact on diversities of cellular processes such as signal transduction and immune response. Many well represented domains recognize and bind to primary sequences less than 10 amino acids in length called Short Linear Motifs (SLiMs).

Results

In this study, we systematically studied the evolutionary conservation of SLiMs recognized by SH2, SH3 and Ser/Thr Kinase domains in both ordered and disordered protein regions. Disordered protein regions are protein sequences that lack a fixed three-dimensional structure under putatively native conditions. We find that, in all these domains examined, SLiMs are more conserved in disordered regions. This trend is more evident in those protein functional groups that are frequently reported to interact with specific domains.

Conclusion

The correlation between SLiM conservation with disorder prediction demonstrates that functional SLiMs recognized by each domain occur more often in disordered as compared to structured regions of proteins.
In silico comparison of transcript abundances during Arabidopsis thaliana and Glycine max resistance to Fusarium virguliforme
Authors: Yuan Jiazheng , Zhu Mengxia , Lightfoot David A , Iqbal M Javed , Yang Jack Y , Meksem Khalid
Published: September 2008

Background

Sudden death syndrome (SDS) of soybean (Glycine max L. Merr.) is an economically important disease, caused by the semi-biotrophic fungus Fusarium solani f. sp. glycines, recently renamed Fusarium virguliforme (Fv). Due to the complexity and length of the soybean-Fusarium interaction, the molecular mechanisms underlying plant resistance and susceptibility to the pathogen are not fully understood. F. virguliforme has a very wide host range for the ability to cause root rot and a very narrow host range for the ability to cause a leaf scorch. Arabidopsis thaliana is a host for many types of phytopathogens including bacteria, fungi, viruses and nematodes. Deciphering the variations among transcript abundances (TAs) of functional orthologous genes of soybean and A. thaliana involved in the interaction will provide insights into plant resistance to F. viguliforme.

Results

In this study, we reported the analyses of microarrays measuring TA in whole plants after A. thaliana cv 'Columbia' was challenged with fungal pathogen F. virguliforme. Infection caused significant variations in TAs. The total number of increased transcripts was nearly four times more than that of decreased transcripts in abundance. A putative resistance pathway involved in responding to the pathogen infection in A. thaliana was identified and compared to that reported in soybean.

Conclusion

Microarray experiments allow the interrogation of tens of thousands of transcripts simultaneously and thus, the identification of plant pathways is likely to be involved in plant resistance to Fusarial pathogens. Dissection of the set functional orthologous genes between soybean and A. thaliana enabled a broad view of the functional relationships and molecular interactions among plant genes involved in F. virguliforme resistance.
Analyzing adjuvant radiotherapy suggests a non monotonic radio-sensitivity over tumor volumes
Authors: Yang Jack Y , Niemierko Andrzej , Yang Mary Qu , Deng Youping
Published: September 2008

Background

Adjuvant Radiotherapy (RT) after surgical removal of tumors proved beneficial in long-term tumor control and treatment planning. For many years, it has been well concluded that radio-sensitivities of tumors upon radiotherapy decrease according to the sizes of tumors and RT models based on Poisson statistics have been used extensively to validate clinical data.

Results

We found that Poisson statistics on RT is actually derived from bacterial cells despite of many validations from clinical data. However cancerous cells do have abnormal cellular communications and use chemical messengers to signal both surrounding normal and cancerous cells to develop new blood vessels and to invade, to metastasis and to overcome intercellular spatial confinements in general. We therefore investigated the cell killing effects on adjuvant RT and found that radio-sensitivity is actually not a monotonic function of volume as it was believed before. We present detailed analysis and explanation to justify above statement. Based on EUD, we present an equivalent radio-sensitivity model.

Conclusion

We conclude that radio sensitivity is a sophisticated function over tumor volumes, since tumor responses upon radio therapy also depend on cellular communications.
Elevated CXCL12 expression in the bone marrow of NOD mice is associated with altered T cell and stem cell trafficking and diabetes development
Authors: Leng Qibin , Nie Yuchun , Zou Yongrui , Chen Jianzhu
Published: September 2008

Background

Type I diabetes (TID) is an autoimmune disease resulting from destruction of the insulin-producing β-cells by autoreactive T cells. Studies have shown that polymorphisms of chemokine CXCL12 gene are linked to TID in humans. In non-obese diabetic (NOD) mice, which are predisposed to develop the disease, reduction of CXCL12 level leads to significant delays in the onset of diabetes. Despite these initial observations, however, how CXCL12 affects development of TID has not been fully investigated.

Results

We found that the level of CXCL12 transcript is significantly elevated in the bone marrow of NOD mice as compared to Balb/c and C57BL/6 mice. Correspondingly, naïve T cells, regulatory T cells and hematopoietic stem cells (HSC) accumulate in the bone marrow of NOD mice. Treatment of NOD mice with AMD3100, an antagonist for CXCL12's receptor CXCR4, mobilizes T cells and HSC from the bone marrow to the periphery, concomitantly inhibits insulitis and delays the onset of diabetes.

Conclusion

These results suggest that the elevated CXCL12 expression promotes TID in NOD mice by altering T cell and hematopoietic stem cell trafficking. The findings highlight the potential usefulness of AMD3100 to treat or prevent TID in humans.
Predictive analysis of transmissible quinolone resistance indicates Stenotrophomonas maltophilia as a potential source of a novel family of Qnr determinants
Authors: Sánchez María B , Hernández Alvaro , Rodríguez-Martínez José M , Martínez-Martínez Luis , Martínez José L
Published: September 2008

Background

Predicting antibiotic resistance before it emerges at clinical settings constitutes a novel approach for preventing and fighting resistance of bacterial pathogens. To analyse the possibility that novel plasmid-encoded quinolone resistance determinants (Qnr) can emerge and disseminate among bacterial pathogens, we searched the presence of those elements in nearly 1000 bacterial genomes and metagenomes.

Results

We have found a number of novel potential qnr genes in the chromosomes of aquatic bacteria and in metagenomes from marine organisms. Functional studies of the Stenotrophomonas maltophilia Smqnr gene show that plasmid-encoded SmQnr confers quinolone resistance upon its expression in a heterologous host.

Conclusion

Altogether, the data presented in our work support the notion that predictive studies on antibiotic resistance are feasible, using currently available information on bacterial genomes and with the aid of bioinformatic and functional tools. Our results confirm that aquatic bacteria can be the origin of plasmid-encoded Qnr, and highlight the potential role of S. maltophilia as a source of novel Qnr determinants.
The HCV Synthesis Project: Scope, methodology, and preliminary results
Authors: Stern Rebecca K , Hagan Holly , Lelutiu-Weinberger Corina , Des Jarlais Don , Scheinmann Roberta , Strauss Shiela , Pouget Enrique R , Flom Peter
Published: September 2008

Background

The hepatitis C virus (HCV) is hyper-endemic in injecting drug users. There is also excess HCV among non-injection drug users who smoke, snort, or sniff heroin, cocaine, crack, or methamphetamine.

Methods

To summarize the research literature on HCV in drug users and identify gaps in knowledge, we conducted a synthesis of the relevant research carried out between 1989 and 2006. Using rigorous search methods, we identified and extracted data from published and unpublished reports of HCV among drug users. We designed a quality assurance system to ensure accuracy and consistency in all phases of the project. We also created a set of items to assess study design quality in each of the reports we included.

Results

We identified 629 reports containing HCV prevalence rates, incidence rates and/or genotype distribution among injecting or non-injecting drug user populations published between January 1989 and December 2006. The majority of reports were from Western Europe (41%), North America (26%), Asia (11%) and Australia/New Zealand (10%). We also identified reports from Eastern Europe, South America, the Middle East, and the Caribbean. The number of publications reporting HCV rates in drug users increased dramatically between 1989 and 2006 to 27–52 reports per year after 1998.

Conclusion

The data collection and quality assurance phases of the HCV Synthesis Project have been completed. Recommendations for future research on HCV in drug users have come out of our data collection phase. Future research reports can enhance their contributions to our understanding of HCV etiology by clearly defining their drug user participants with respect to type of drug and route of administration. Further, the use of standard reporting methods for risk factors would enable data to be combined across a larger set of studies; this is especially important for HCV seroconversion studies which suffer from small sample sizes and low power to examine risk factors.
Caregivers' active role in palliative home care – to encourage or to dissuade? A qualitative descriptive study
Authors: Weibull Anna , Olesen Frede , Neergaard Mette Asbjoern
Published: September 2008

Background

Spouses' involvement in palliative care is often a prerequisite for home death, but it is unclear whether active involvement of the spouse, e.g. administering and being in charge of oral or subcutaneous medication or taking care of the patient's personal hygiene, could be harmful or have negative effects on the spouse's experience of the palliative course of disease. The aim of this study was to explore the impact of bereaved spouses' active involvement in medical and physical care on their experience of the palliative course of disease.

Methods

The study was a qualitative, descriptive study based on semi-structured individual interviews with seven bereaved spouses.

Results

Four main categories were found: Degree of involvement, Positive and Negative impact and Prerequisites. The prerequisites found for a positive outcome were Safety (24-hour back-up), Confidence (Professionals' confidence in the spouses' abilities) and Dialog (Spouses' influence on decision-making and being asked).

Conclusion

The results from this study identified important issues whenever spouses take an active part in medical treatment and physical care of critically ill patients in palliative care. The results question the previous research that active involvement of family care givers could be harmful and add preconditions to a positive outcome. More research into these preconditions is needed.
Association of alleles carried at TNFA -850 and BAT1-22 with Alzheimer's disease
Authors: Gnjec Anastazija , D'Costa Katarzyna J , Laws Simon M , Hedley Ross , Balakrishnan Kelvin , Taddei Kevin , Martins Georgia , Paton Athena , Verdile Giuseppe , Gandy Samuel E , Broe G Anthony , Brooks William S , Bennett Hayley , Piguet Olivier , Price Patricia , Miklossy Judith , Hallmayer Joachim , McGeer Patrick L , Martins Ralph N
Published: September 2008

Background

Inflammatory changes are a prominent feature of brains affected by Alzheimer's disease (AD). Activated glial cells release inflammatory cytokines which modulate the neurodegenerative process. These cytokines are encoded by genes representing several interleukins andTNFA, which are associated with AD. The gene coding for HLA-B associated transcript 1 (BAT1) lies adjacent toTNFAin the central major histocompatibility complex (MHC). BAT1, a member of the DEAD-box family of RNA helicases, appears to regulate the production of inflammatory cytokines associated with AD pathology. In the current studyTNFAand BAT1 promoter polymorphisms were analysed in AD and control cases and BAT1 mRNA levels were investigated in brain tissue from AD and control cases.

Methods

Genotyping was performed for polymorphisms at positions -850 and -308 in the proximal promoter ofTNFAand position -22 in the promoter ofBAT1. These were investigated singly or in haplotypic association in a cohort of Australian AD patients with AD stratified on the basis of theirAPOEε4 genotype. Semi-quantitative RT-PCR was also performed for BAT1 from RNA isolated from brain tissue from AD and control cases.

Results

APOEε4 was associated with an independent increase in risk for AD in individuals withTNFA-850*2, while carriage ofBAT1-22*2 reduced the risk for AD, independent ofAPOEε4 genotype. Semi-quantitative mRNA analysis in human brain tissue showed elevated levels ofBAT1mRNA in frontal cortex of AD cases.

Conclusion

These findings lend support to the application ofTNFAandBAT1polymorphisms in early diagnosis or risk assessment strategies for AD and suggest a potential role for BAT1 in the regulation of inflammatory reactions in AD pathology.
Unravelling the adaptation responses to osmotic and temperature stress in Chromohalobacter salexigens, a bacterium with broad salinity tolerance
Authors: Vargas Carmen , Argandoña Montserrat , Reina-Bueno Mercedes , Rodríguez-Moya Javier , Fernández-Aunión Cristina , Nieto Joaquín J
Published: September 2008

Chromohalobacter salexigens, a Gammaproteobacterium belonging to the familyHalomonadaceae, shows a broad salinity range for growth. Osmoprotection is achieved by the accumulation of compatible solutes either by transport (betaine, choline) or synthesis (mainly ectoine and hydroxyectoine). Ectoines can play additional roles as nutrients and, in the case of hydroxyectoine, in thermotolerance. A supplementary solute, trehalose, not present in cells grown at 37°C, is accumulated at higher temperatures, suggesting its involvement in the response to heat stress. Trehalose is also accumulated at 37°C in ectoine-deficient mutants, indicating that ectoines suppress trehalose synthesis in the wild-type strain. The genes for ectoine (ectABC) and hydroxyectoine (ectD,ectE) production are arranged in three different clusters within theC. salexigenschromosome. In order to cope with changing environment,C. salexigensregulates its cytoplasmic pool of ectoines by a number of mechanisms that we have started to elucidate. This is a highly complex process because (i) hydroxyectoine can be synthesized by other enzymes different to EctD (ii) ectoines can be catabolized to serve as nutrients, (iii) the involvement of several transcriptional regulators (σS, σ32, Fur, EctR) and hence different signal transduction pathways, and (iv) the existence of post-trancriptional control mechanisms. In this review we summarize our present knowledge on the physiology and genetics of the processes allowingC. salexigensto cope with osmotic stress and high temperature, with emphasis on the transcriptional regulation.