bluuebunny/crossref_metadata_2025_split huggingface dataset:
The bell tolls for the relationship between house dust mite exposure and asthma in childhood
Authors: Almqvist Catarina , Marks Guy , Li Qiang , Crisafulli Daniel , Tovey Euan 
Published: September 2008

Prior evidence has suggested a direct relationship between the level of house dust mite (HDM) allergen exposure, sensitisation and asthma. A recent cross-sectional study indicated a bell-shaped relationship between HDM exposure and sensitisation [1]. We examined the effects of cumulative HDM allergen exposure during the first 5 years of life on outcomes at age 5 years in Sydney, a high HDM environment.In the Childhood Asthma Prevention Study, bed dust samples collected at 3, 6, 9 and 12 months and then 6-monthly (total 6615 samples) until age 5 years were analysed for HDM allergen by ELISA. At five years, 516 children were assessed for wheeze and asthma by questionnaires and spirometry, and 488 for sensitisation by skin test. Time-weighted average HDM allergen concentration was estimated for each individual. The range was divided into quintiles with cut-points being 3,5; 7,8; 13,5 and 23,4 ug Der p 1/g. The association between HDM levels and outcomes was analysed with chi-square test, adjusting for confounders.The figure shows the prevalence of outcomes by quintile of time-weighted average of HDM allergen.In this birth cohort, there is a bell-shaped dose response between HDM levels and sensitisation and asthma. This may reflect tolerance to HDM allergen or be attributable to protection from associated exposures, and prompts further research on the mechanisms.
Effectiveness of group counselling for smoking cessation in hospital staff
Authors: Schoonis A. , Celis G. , Wuyts W. , Lemaigre V. , Nackaerts K. 
Published: September 2008

Smoking prevalence among hospital staff is still considerable. It is well known that smoking cessation is difficult to establish without any help. Group counselling is effective for smoking cessation. In 2004, therefore, we decided to offer group counselling for smoking cessation to our hospital staff.(1) To assess the efficacy of group counselling given by a multidisciplinary team of healthcare professionals.(2) To determine the quit rate after group counselling in hospital staff.The program is based on 10 group sessions of 90 min each. Each group contains a maximum of 16 participants. The group sessions were led by a nurse specialized in smoking cessation and consisted of education and behavioural interventions provided by health care professionals (respiratory physician, psychologist and a dietician). To improve smoking cessation motivation, spirometry (FEV1 and FVC) and exhaled CO were measured both at the start and at the end of the group counselling.In total, 38 participants of 3 different groups entered group counselling. The mean age was 48 years, and 71% was female. They smoked an average of 20 cigarettes per day. Based on exhaled CO measurements and self-reports, smoking cessation, the quit rates after 6 months, 1 year and 2 years were, 27/35 (77%), 25/35 (72%) and 23/35 (66%), respectively.Group counselling program on smoking cessation in hospital staff based on 10 group sessions was able to induce a remarkably high amount of quitters. The hospital setting offered the opportunity to meet the group participants frequently afterwards, what might have helped in keeping the quitting results at about the same level, even after 2 years’ follow-up.
Impact of environmental factors on lung defences
Authors: Olivieri D. , Scoditti E. 
Published: September 2008

The lungs are one of the most important organs exposed to environmental agents. The lungs have the ability to protect themselves by both immunological and nonimmunological mechanisms. An individual's susceptibility to the impact of environmental agents will determine their adverse effects.This article focuses on air pollution, in particular ozone (O3), nitrogen dioxide (NO2), particulate matter (PM) and sulphur dioxide (SO2). O3inhalation first modifies the ciliary cells. O3is an extremely strong oxidant, since it increases the permeability of epithelial cells and decreases mucociliary clearance. NO2is a less potent and less reactive oxidant pollutant and impairs the function of epithelial cells and alveolar macrophages. PM induces oxidative stress in macrophages and epithelial cells, and increases tumour necrosis factor-β, interleukin (IL)-6, interferon-γ, transforming growth factor-β and nuclear factor-▒B. Diesel exhaust particulate, contained in PM, increases IL-8 production. High concentrations of SO2increase the production of reactive oxygen species in the lungs.In conclusion, air pollution certainly interferes with aspecific and specific lung defences, thus facilitating the development of pulmonary diseases, such as exacerbation of chronic obstructive pulmonary disease, allergies and asthma.
Impact of bacterial infections on airway diseases: FIGURE 1.
Authors: Toews G. B. 
Published: September 2008

Bacterial infections play an important role as aetiologic agents in acute exacerbations of chronic obstructive pulmonary disease (COPD). Modern investigational tools, including bronchoscopy, microbial molecular epidemiology and measurement of specific immunity have established that bacteria cause up to 50% of acute exacerbations in COPD.Acute exacerbations have enormous economic costs and contribute to morbidity, mortality and impairment in health related quality of life. Chronic bacterial persistence in the lower airways and lower respiratory tract in patients with COPD is not innocuous. It is likely to contribute to persistent airway inflammation and might contribute to acute airway exacerbations or progression of airway obstruction. Further investigation is required in these fertile areas of investigation.Bacteria also play a role in asthma exacerbations, but their role is less well defined than with patients with COPD.Mycoplasma pneumoniaemay be associated with asthma chronicity. Chronic airway infection models document thatM. pneumoniaeplays a role in airway remodelling, including angiogenesis, vascular remodelling and airway wall thickening.Recent studies have identified patients with asthma as an at-risk group for invasive pneumococcal disease. The feasibility and cost effectiveness of a pneumococcal vaccination strategy among persons with asthma deserves careful, immediate attention.
Developmental factors as determinants of risk for infections and atopy in childhood: FIGURE 1.
Authors: Holt P. G. 
Published: September 2008

The nature of the relationship between infections and allergy in children continues to be the subject of vigorous debate, in particular the issue of whether the increased frequency of wheezing respiratory infections in children is a cause or a consequence of atopy.Recent evidence suggests a subtle twist to this argument, notably that the genetic risk for susceptibility to both atopy and respiratory infections may involve a common set of genetic variations related to the efficiency of maturation of immune function in early post-natal life.
Prevention of paediatric respiratory tract infections: emphasis on the role of OM-85: TABLE 1—
Authors: Schaad U. B. 
Published: September 2008

The burden of respiratory tract infections in paediatrics is extremely high, in both industrialised and developing countries. Because adequate diagnosis and causative therapies of these often recurrent respiratory tract infections bear substantial limits, preventive measures deserve priority. The mainstays are parent education, active immunisation strategies and nonspecific immunostimulation with bacterial products.This article summarises the five key studies on the use of the immunoactive agent OM-85 (Broncho-Vaxom) for prevention of recurrent respiratory tract infections in children. Such bacterial immunostimulants are especially indicated for young infants and children who are known and/or expected to suffer from at least three respiratory tract infections per winter season.
Inhaler choice in primary practice
Authors: Chapman K. R. , Voshaar T. H. , Virchow J. C. 
Published: September 2008

A broad range of inhaler devices is available for physicians to prescribe. Although newer devices are often easier to use than conventional pressurised metered-dose inhalers (pMDIs), many patients still use inhalers sub-optimally. Physicians must become familiar with the characteristics of several inhalers and choose the device that their patients can use correctly and beneficially if they are to prescribe successfully to those with chronic obstructive pulmonary disease (COPD). The selection of a device may also be influenced by patient comorbidities and by their ability to handle and inhale correctly from the device. A further challenge in the COPD setting is measuring the desired treatment outcome.A simple algorithm or checklist can guide device selection in primary care. The device must be affordable for the patient, the patient must be able to handle it correctly and the practitioner or other trained professional should monitor that it is being used correctly. The patient's and physician's preferences should also be taken into account. The most important device-handling skills that should be assessed are whether the patient can: properly prepare and actuate the device; take an adequate inspiration; and coordinate actuation of a pMDI with inspiration.Testing the practicality and advantages of such checklists will mean better use can be made of the inhaler types currently available as well as newer designs. In the interim, caregiver and patient education are needed.
Cost of asthma in the Asia-Pacific region
Authors: Lai C. K. W. , Kim Y-Y. , Kuo S-H. , Spencer M. , Williams A. E. 
Published: September 2008

The substantial morbidity caused by asthma suggests that the disease is associated with a large economic burden. The current study analysed the burden of asthma in eight countries in the Asia-Pacific region.Responses to questions regarding resource use from a survey of people with asthma were analysed. Unit costs were obtained for each resource use element. Individual patient costs were estimated and means calculated for each country. A multivariate model was developed to identify potential predictors of resource use.Annual per-patient direct costs ranged from US$108 for Malaysia to US$1,010 for Hong Kong. When productivity costs were included, total per-patient societal costs ranged from US$184 in Vietnam to US$1,189 in Hong Kong. Urgent care costs were responsible for 18–90% of total per-patient direct costs. Overall, total per-patient direct costs were equivalent to 13% ofper capitagross domestic product and 300% ofper capitahealthcare spending. Extremes of age, greater severity of asthma, and poorer general health status were predictive of high cost.The per-patient cost of asthma in these countries is high, particularly when seen in the context of overall per-patient healthcare spending. Strategies to improve asthma control are likely to not only improve patient outcomes, but also to decrease societal costs.
Asthma control and its direct healthcare costs: findings using a derived Asthma Control TestTMscore in eight Asia-Pacific areas
Authors: Lai C. K. W. , Kuo S-H. , de Guia T. , Lloyd A. , Williams A. E. , Spencer M. D. 
Published: September 2008

The present authors explored the relationship between asthma control status, measured using a derived Asthma Control TestTM(ACT) score, and utilisation of healthcare and its cost in eight Asia-Pacific areas.Patients were included if they were aged ≥12 yrs and had participated in a recent survey of asthma patients. Patient-reported frequency of healthcare resource use was used to estimate the cost of asthma care. The ACT score was derived from survey questions identical or similar to the items comprising the ACT.An ACT score was derived for 2,062 patients, of whom 59% (1,220) scored <20, suggesting that their asthma was not well controlled, and with 21% (423) scoring <15, suggesting poorly controlled asthma. The mean per-patient annual cost of asthma management for patients with a derived ACT of <15 was US$861 (95% confidence interval: US$686–1,042); US$319 (US$286–357) for patients with a derived ACT score of 15–19, and US$193 (US$173–214) for patients with a derived ACT score of ≥20. A higher derived ACT score was associated with significantly lower annual expenditure on asthma management.Poorer asthma control was associated with an increased frequency of all unscheduled healthcare and elevated cost. This finding was consistent across a range of Asia-Pacific areas.
A method for detecting epistasis in genome-wide studies using case-control multi-locus association analysis
Authors: Gayán Javier , González-Pérez Antonio , Bermudo Fernando , Sáez María Eugenia , Royo Jose Luis , Quintas Antonio , Galan Jose Jorge , Morón Francisco Jesús , Ramirez-Lorca Reposo , Real Luis Miguel , Ruiz Agustín 
Published: September 2008

Abstract

Background
The difficulty in elucidating the genetic basis of complex diseases roots in the many factors that can affect the development of a disease. Some of these genetic effects may interact in complex ways, proving undetectable by current single-locus methodology.

Results
We have developed an analysis tool called Hypothesis Free Clinical Cloning (HFCC) to search for genome-wide epistasis in a case-control design. HFCC combines a relatively fast computing algorithm for genome-wide epistasis detection, with the flexibility to test a variety of different epistatic models in multi-locus combinations. HFCC has good power to detect multi-locus interactions simulated under a variety of genetic models and noise conditions. Most importantly, HFCC can accomplish exhaustive genome-wide epistasis search with large datasets as demonstrated with a 400,000 SNP set typed on a cohort of Parkinson's disease patients and controls.

Conclusion
With the current availability of genetic studies with large numbers of individuals and genetic markers, HFCC can have a great impact in the identification of epistatic effects that escape the standard single-locus association analyses.
The FEATURE framework for protein function annotation: modeling new functions, improving performance, and extending to novel applications
Authors: Halperin Inbal , Glazer Dariya S , Wu Shirley , Altman Russ B 
Published: September 2008

Abstract
Structural genomics efforts contribute new protein structures that often lack significant sequence and fold similarity to known proteins. Traditional sequence and structure-based methods may not be sufficient to annotate the molecular functions of these structures. Techniques that combine structural and functional modeling can be valuable for functional annotation. FEATURE is a flexible framework for modeling and recognition of functional sites in macromolecular structures. Here, we present an overview of the main components of the FEATURE framework, and describe the recent developments in its use. These include automating training sets selection to increase functional coverage, coupling FEATURE to structural diversity generating methods such as molecular dynamics simulations and loop modeling methods to improve performance, and using FEATURE in large-scale modeling and structure determination efforts.
Up-regulation of endothelin type B receptors in the human internal mammary artery in culture is dependent on protein kinase C and mitogen-activated kinase signaling pathways
Authors: Nilsson David , Gustafsson Lotta , Wackenfors Angelica , Gesslein Bodil , Edvinsson Lars , Paulsson Per , Ingemansson Richard , Malmsjö Malin 
Published: September 2008

Abstract

Background
Up-regulation of vascular endothelin type B (ETB) receptors is implicated in the pathogenesis of cardiovascular disease. Culture of intact arteries has been shown to induce similar receptor alterations and has therefore been suggested as a suitable method for, ex vivo, in detail delineation of the regulation of endothelin receptors. We hypothesize that mitogen-activated kinases (MAPK) and protein kinase C (PKC) are involved in the regulation of endothelin ETB receptors in human internal mammary arteries.

Methods
Human internal mammary arteries were obtained during coronary artery bypass graft surgery and were studied before and after 24 hours of organ culture, using in vitro pharmacology, real time PCR and Western blot techniques. Sarafotoxin 6c and endothelin-1 were used to examine the endothelin ETA and ETB receptor effects, respectively. The involvement of PKC and MAPK in the endothelin receptor regulation was examined by culture in the presence of antagonists.

Results
The endohtelin-1-induced contraction (after endothelin ETB receptor desensitization) and the endothelin ETA receptor mRNA expression levels were not altered by culture. The sarafotoxin 6c contraction, endothelin ETB receptor protein and mRNA expression levels were increased after organ culture. This increase was antagonized by; (1) PKC inhibitors (10 μM bisindolylmaleimide I and 10 μM Ro-32-0432), and (2) inhibitors of the p38, extracellular signal related kinases 1 and 2 (ERK1/2) and C-jun terminal kinase (JNK) MAPK pathways (10 μM SB203580, 10 μM PD98059 and 10 μM SP600125, respectively).

Conclusion
In conclusion, PKC and MAPK seem to be involved in the up-regulation of endothelin ETB receptor expression in human internal mammary arteries. Inhibiting these intracellular signal transduction pathways may provide a future therapeutic target for hindering the development of vascular endothelin ETB receptor changes in cardiovascular disease.
Rabies trend in China (1990–2007) and post-exposure prophylaxis in the Guangdong province
Authors: Si Han , Guo Zhong-Min , Hao Yuan-Tao , Liu Yu-Ge , Zhang Ding-Mei , Rao Shao-Qi , Lu Jia-Hai 
Published: September 2008

Abstract

Background
Rabies is a major public-health problem in developing countries such as China. Although the recent re-emergence of human rabies in China was noted in several epidemiological studies, little attention was paid to the reasons behind this phenomenon paralleling the findings of the previous reports. The purpose of this study is thus first to characterize the current trends of human rabies in China from 1990 to 2007, and then to define better recommendations for improving the post-exposure prophylaxis (PEP) schedules delivered to rabies patients.

Methods
The most updated epidemiological data for 22527 human rabies cases from January 1990 to July 2007, retrieved from the surveillance database of reportable diseases managed by the Ministry of Health of China, were analysed. To investigate the efficiency for the post-exposure treatment of rabies, the details of 244 rabies patients, including their anti-rabies treatment of injuries or related incidents, were ascertained in Guangdong provincial jurisdiction. The risk factors to which the patients were predisposed or the regimens given to 80 patients who received any type of PEP were analysed to identify the reasons for the PEP failures.

Results
The results from analysis of the large number of human rabies cases showed that rabies in China was largely under control during the period 1990–1996. However, there has been a large jump in the number of reported rabies cases since 2001 up to a new peak (with an incidence rate of 0.20 per 100000 people) that was reached in 2004, and where the level has remained until present. Then, we analysed the PEP in 244 rabies cases collected in the Guangdong province in 2003 and 2004, and found that 67.2% of the patients did not seek medical services or did not receive any PEP. Further analysis of PEP for the 80 rabies patients who received any type of PEP indicated that almost all of the patients did not receive proper or timely treatment on the wounds or post-exposure vaccination or rabies immunoglobulins.

Conclusion
While the issue of under-reporting of rabies in previous years may well be a factor in the apparent upwards trend of human rabies in recent years, the analysis of PEP in the Guangdong province provides evidence that suggests that the failure to receive PEP was a major factor in the number of human cases in China. Thus, the data underline the need for greatly improved availability and timely application of high-quality anti-rabies biologicals, both vaccines and immunoglobulins, in the treatment of human bite victims. Controlling dog rabies through pet vaccination schemes may also play a huge role in reducing the rate of human exposure. Education of the public, health care staff and veterinarians will also help to change the current situation.
BRAF, KRAS and PIK3CA mutations in colorectal serrated polyps and cancer: Primary or secondary genetic events in colorectal carcinogenesis?
Authors: Velho Sérgia , Moutinho Cátia , Cirnes Luís , Albuquerque Cristina , Hamelin Richard , Schmitt Fernando , Carneiro Fátima , Oliveira Carla , Seruca Raquel 
Published: September 2008

Abstract

Background

BRAF, KRAS and PIK3CA mutations are frequently found in sporadic colorectal cancer (CRC). In contrast to KRAS and PIK3CA mutations, BRAF mutations are associated with tumours harbouring CpG Island methylation phenotype (CIMP), MLH1 methylation and microsatellite instability (MSI). We aimed at determine the frequency of KRAS, BRAF and PIK3CA mutations in the process of colorectal tumourigenesis using a series of colorectal polyps and carcinomas. In the series of polyps CIMP, MLH1 methylation and MSI were also studied.

Methods
Mutation analyses were performed by PCR/sequencing. Bisulfite treated DNA was used to study CIMP and MLH1 methylation. MSI was detected by pentaplex PCR and Genescan analysis of quasimonomorphic mononucleotide repeats. Chi Square test and Fisher's Exact test were used to perform association studies.

Results

KRAS, PIK3CA or BRAF occur in 71% of polyps and were mutually exclusive. KRAS mutations occur in 35% of polyps. PIK3CA was found in one of the polyps. V600E BRAF mutations occur in 29% of cases, all of them classified as serrated adenoma. CIMP phenotype occurred in 25% of the polyps and all were mutated for BRAF. MLH1 methylation was not detected and all the polyps were microsatellite stable. The comparison between the frequency of oncogenic mutations in polyps and CRC (MSI and MSS) lead us to demonstrate that KRAS and PIK3CA are likely to precede both types of CRC. BRAF mutations are likely to precede MSI carcinomas since the frequency found in serrated polyps is similar to what is found in MSI CRC (P = 0.9112), but statistically different from what is found in microsatellite stable (MSS) tumours (P = 0.0191).

Conclusion
Our results show that BRAF, KRAS and PIK3CA mutations occur prior to malignant transformation demonstrating that these oncogenic alterations are primary genetic events in colorectal carcinogenesis. Further, we show that BRAF mutations occur in association with CIMP phenotype in colorectal serrated polyps and verified that colorectal serrated polyps and MSI CRC show a similar frequency of BRAF mutations. These results support that BRAF mutations harbour a mild oncogenic effect in comparison to KRAS and suggest that BRAF mutant colorectal cells need to accumulate extra epigenetic alterations in order to acquire full transformation and evolve to MSI CRC.