bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

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

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

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.
Predicting violent infractions in a Swiss state penitentiary: A replication study of the PCL-R in a population of sex and violent offenders
Authors: Endrass Jérôme , Rossegger Astrid , Urbaniok Frank , Laubacher Arja , Vetter Stefan
Published: September 2008

Background

Research conducted with forensic psychiatric patients found moderate correlations between violence in institutions and psychopathy. It is unclear though, whether the PCL-R is an accurate instrument for predicting aggressive behavior in prisons. Results seem to indicate that the instrument is better suited for predicting verbal rather than physical aggression of prison inmates.

Methods

PCL-R scores were assessed for a sample of 113 imprisoned sex and violent offenders in Switzerland. Logistic regression analyses were used to estimate physical and verbal aggression as a function of the PCL-R sum score. Additionally, stratified analyses were conducted for Factor 1 and 2. Infractions were analyzed as to their motives and consequences.

Results

The mean score of the PCL-R was 12 points. Neither the relationship between physical aggression and the sum score of the PCL-R, nor the relationship between physical aggression and either of the two factors of the PCL-R were significant. Both the sum score and Factor 1 predicted the occurrence of verbal aggression (AUC = 0.70 and 0.69), while Factor 2 did not.

Conclusion

Possible explanations are discussed for the weak relationship between PCL-R scores and physically aggressive behavior during imprisonment. Some authors have discussed whether the low base rate of violent infractions can be considered an explanation for the non-significant relation between PCL-R-score and violence. The base rate in this study, however, with 27%, was not low. It is proposed that the distinction between reactive and instrumental motives of institutional violence must be considered when examining the usefulness of the PCL-R in predicting in-prison physical aggressive behavior.
A 6-week, multicentre, randomised, double-blind, double-dummy, active-controlled, clinical safety study of lumiracoxib and rofecoxib in osteoarthritis patients
Authors: Stricker Kirstin , Yu Sue , Krammer Gerhard
Published: September 2008

Background

Lumiracoxib is a selective cyclooxygenase-2 inhibitor effective in the treatment of osteoarthritis (OA) with a superior gastrointestinal (GI) safety profile as compared to traditional non-steroidal anti-inflammatory drugs (NSAIDs, ibuprofen and naproxen). This safety study compared the GI tolerability, the blood pressure (BP) profile and the incidence of oedema with lumiracoxib and rofecoxib in the treatment of OA. Rofecoxib was withdrawn worldwide due to an associated increased risk of CV events and lumiracoxib has been withdrawn from Australia, Canada, Europe and a few other countries following reports of suspected adverse liver reactions.

Methods

This randomised, double-blind study enrolled 309 patients (aged greater than or equal to 50 years) with primary OA across 51 centres in Europe. Patients were randomly allocated to receive either lumiracoxib 400 mg od (four times the recommended dose in OA) (n = 154) or rofecoxib 25 mg od (n = 155). The study was conducted for 6 weeks and assessments were performed at Weeks 3 and 6. The primary safety measures were the incidence of predefined GI adverse events (AEs) and peripheral oedema. The secondary safety measures included effect of treatment on the mean sitting systolic and diastolic blood pressure (msSBP and msDBP). Tolerability of lumiracoxib 400 mg was assessed by the incidence of AEs.

Results

Lumiracoxib and rofecoxib displayed similar GI safety profiles with no statistically significant difference in predefined GI AEs between the two groups (43.5% vs. 37.4%, respectively). The incidence and severity of individual predefined GI AEs was comparable between the two groups. The incidence of peripheral oedema was low and identical in both the groups (n = 9, 5.8%). Only one patient in the lumiracoxib group and three patients in the rofecoxib group had a moderate or severe event. At Week 6 there was a significantly lower msSBP and msDBP in the lumiracoxib group compared to the rofecoxib group (p < 0.05). A similar percentage of patients in both groups showed an improvement in target joint pain and disease activity. The tolerability profile was similar in both the treatment groups.

Conclusion

Lumiracoxib 400 mg od (four times the recommended dose in OA) provided a comparable GI safety profile to rofecoxib 25 mg od (therapeutic dose). However, lumiracoxib was associated with a significantly better BP profile as compared to rofecoxib.

Trial registration number -

NCT00637949
Phosphoribosyl pyrophosphate synthetase activity affects growth and riboflavin production in Ashbya gossypii
Authors: Jiménez Alberto , Santos María A , Revuelta José L
Published: September 2008

Background

Phosphoribosyl pyrophosphate (PRPP) is a central compound for cellular metabolism and may be considered as a link between carbon and nitrogen metabolism. PRPP is directly involved in the de novo and salvage biosynthesis of GTP, which is the immediate precursor of riboflavin. The industrial production of this vitamin using the fungus Ashbya gossypii is an important biotechnological process that is strongly influenced by substrate availability.

Results

Here we describe the characterization and manipulation of two genes of A. gossypii encoding PRPP synthetase (AGR371C and AGL080C). We show that the AGR371C and AGL080C gene products participate in PRPP synthesis and exhibit inhibition by ADP. We also observed a major contribution of AGL080C to total PRPP synthetase activity, which was confirmed by an evident growth defect of the Δagl080c strain. Moreover, we report the overexpression of wild-type and mutant deregulated isoforms of Agr371cp and Agl080cp that significantly enhanced the production of riboflavin in the engineered A. gossypii strains.

Conclusion

It is shown that alterations in PRPP synthetase activity have pleiotropic effects on the fungal growth pattern and that an increase in PRPP synthetase enzymatic activity can be used to enhance riboflavin production in A. gossypii.
Differences in Fcgamma receptor IIa genotypes and IgG subclass pattern of anti-malarial antibodies between sympatric ethnic groups in Mali
Authors: Israelsson Elisabeth , Vafa Manijeh , Maiga Bakary , Lysén Anna , Iriemenam Nnaemeka C , Dolo Amagana , Doumbo Ogobara K , Troye-Blomberg Marita , Berzins Klavs
Published: September 2008

Background

The Ig Fc receptor family is an important link between the humoral and cellular immune systems. The association of a dimorphism in amino acid 131 (R/H) of the FcγRIIa with malaria severity, the R-allele being associated with a milder disease outcome, led to the investigation of the possible impact of this polymorphism in the interethnic difference in malaria susceptibility seen between the Fulani and Dogon in Mali.

Methods

Plasma from individuals from Mali (164 Fulani and 164 Dogon) were analysed for malaria-reactive and total IgG subclass antibodies using ELISA, and the same individuals were also genotyped for the FcγRIIa R131H polymorphism using RFLP-PCR. Statistical analyses of the IgG subclass levels were done by unpaired t-test and ANOVA, and genotype differences were tested by χ2-test.

Results

While the two ethnic groups showed a similar frequency of the FcγRIIa 131 R/H heterozygote genotype, 131R/R dominated over the 131 H/H genotype in the Dogon whereas the Fulani presented a similar frequency of the two homozygote genotypes. The two alleles were evenly distributed in the Fulani, while the Dogon were clearly biased towards the R-allele. The Fulani showed higher levels of anti-malarial IgG1, -2 and -3 antibodies, with a higher proportion of IgG2, than the Dogon. In the Fulani, H-allele carriers had higher anti-malarial IgG2 levels than R/R homozygotes, while in the Dogon, the R-allele carriers showed the higher IgG2 levels. For anti-malarial IgG3, the R-allele carriers in the Fulani had higher levels than the H/H homozygotes.

Conclusion

Taken together, the results showed marked interethnic differences in FcγRIIa R131H genotypes. Furthermore, the results indicate that the FcγRIIa R131H genotype may influence the IgG subclass responses related to protection against malaria, and that IgG2 may be of importance in this context.
Is bioelectrical impedance accurate for use in large epidemiological studies?
Authors: Dehghan Mahshid , Merchant Anwar T
Published: September 2008

Percentage of body fat is strongly associated with the risk of several chronic diseases but its accurate measurement is difficult. Bioelectrical impedance analysis (BIA) is a relatively simple, quick and non-invasive technique, to measure body composition. It measures body fat accurately in controlled clinical conditions but its performance in the field is inconsistent. In large epidemiologic studies simpler surrogate techniques such as body mass index (BMI), waist circumference, and waist-hip ratio are frequently used instead of BIA to measure body fatness. We reviewed the rationale, theory, and technique of recently developed systems such as foot (or hand)-to-foot BIA measurement, and the elements that could influence its results in large epidemiologic studies. BIA results are influenced by factors such as the environment, ethnicity, phase of menstrual cycle, and underlying medical conditions. We concluded that BIA measurements validated for specific ethnic groups, populations and conditions can accurately measure body fat in those populations, but not others and suggest that for large epdiemiological studies with diverse populations BIA may not be the appropriate choice for body composition measurement unless specific calibration equations are developed for different groups participating in the study.
TLR3 and TLR4 expression in healthy and diseased human endometrium
Authors: Allhorn Svenja , Böing Carsten , Koch Andrea A , Kimmig Rainer , Gashaw Isabella
Published: September 2008

Background

Toll-like receptors (TLRs) play an essential role in the innate immune system by initiating and directing immune response to pathogens. TLRs are expressed in the human endometrium and their regulation might be crucial for the pathogenesis of endometrial diseases.

Methods

TLR3 and TLR4 expression was investigated during the menstrual cycle and in postmenopausal endometrium considering peritoneal endometriosis, hyperplasia, and endometrial adenocarcinoma specimens (grade 1 to 3). The expression studies applied quantitative RT-PCR and immunolabelling of both proteins.

Results

TLR3 and TLR4 proteins were mostly localised to the glandular and luminal epithelium. In addition, TLR4 was present on endometrial dendritic cells, monocytes and macrophages. TLR3 and TLR4 mRNA levels did not show significant changes during the menstrual cycle. In patients with peritoneal endometriosis, TLR3 and TLR4 mRNA expression decreased significantly in proliferative diseased endometrium compared to controls. Interestingly, ectopic endometriotic lesions showed a significant increase of TLR3 und TLR4 mRNA expression compared to corresponding eutopic tissues, indicating a local gain of TLR expression. Endometrial hyperplasia and adenocarcinoma revealed significantly reduced receptor levels when compared with postmenopausal controls. The lowest TLR expression levels were determined in poor differentiated carcinoma (grade 3).

Conclusion

Our data suggest an involvement of TLR3 and TLR4 in endometrial diseases as demonstrated by altered expression levels in endometriosis and endometrial cancer.
Erythropoietin enhances hippocampal long-term potentiation and memory
Authors: Adamcio Bartosz , Sargin Derya , Stradomska Alicja , Medrihan Lucian , Gertler Christoph , Theis Fabian , Zhang Mingyue , Müller Michael , Hassouna Imam , Hannke Kathrin , Sperling Swetlana , Radyushkin Konstantin , El-Kordi Ahmed , Schulze Lizzy , Ronnenberg Anja , Wolf Fred , Brose Nils , Rhee Jeong-Seop , Zhang Weiqi , Ehrenreich Hannelore
Published: September 2008

Background

Erythropoietin (EPO) improves cognition of human subjects in the clinical setting by as yet unknown mechanisms. We developed a mouse model of robust cognitive improvement by EPO to obtain the first clues of how EPO influences cognition, and how it may act on hippocampal neurons to modulate plasticity.

Results

We show here that a 3-week treatment of young mice with EPO enhances long-term potentiation (LTP), a cellular correlate of learning processes in the CA1 region of the hippocampus. This treatment concomitantly alters short-term synaptic plasticity and synaptic transmission, shifting the balance of excitatory and inhibitory activity. These effects are accompanied by an improvement of hippocampus dependent memory, persisting for 3 weeks after termination of EPO injections, and are independent of changes in hematocrit. Networks of EPO-treated primary hippocampal neurons develop lower overall spiking activity but enhanced bursting in discrete neuronal assemblies. At the level of developing single neurons, EPO treatment reduces the typical increase in excitatory synaptic transmission without changing the number of synaptic boutons, consistent with prolonged functional silencing of synapses.

Conclusion

We conclude that EPO improves hippocampus dependent memory by modulating plasticity, synaptic connectivity and activity of memory-related neuronal networks. These mechanisms of action of EPO have to be further exploited for treating neuropsychiatric diseases.
Increased plasma homocysteine levels in patients with multiple sclerosis and depression
Authors: Triantafyllou Nikolaos , Evangelopoulos Maria-Eleftheria , Kimiskidis Vasilios K , Kararizou Evangelia , Boufidou Fotini , Fountoulakis Konstantinos N , Siamouli Melina , Nikolaou Chrysoula , Sfagos Constantinos , Vlaikidis Nikolaos , Vassilopoulos Dimitrios
Published: September 2008

Background

The aim of the study was to assess the plasma levels of homocysteine in patients with multiple sclerosis (MS) and to investigate whether an association with depression exists.

Methods

Plasma homocysteine (Hcy), vitamin B12 and plasma folate were measured in 65 moderately disabled patients with relapsing/remitting MS (RR-MS) and 60 healthy controls. All subjects were assessed with the Beck Depression Inventory (BDI).

Results

Hcy levels were significantly increased in MS patients compared to controls (13.5 ± 4.7 μmol/l vs 8.5 ± 3.1, p < 0.001). A significant correlation was found between Hcy levels and BDI scores (Pearson r = 0.3025, p < 0.05). Plasma Hcy was not related to Extended Disability Status Scale (EDSS) score, age, disease duration or vitamin B12 and folate.

Conclusion

Moderately disabled MS patients with elevated Hcy levels are particularly prone to develop depressive symptomatology. Further study is warranted in order to elucidate the prognostic and therapeutic implications of this novel finding.
Clinical consequences of asbestos-related diffuse pleural thickening: A review
Authors: Miles Susan E , Sandrini Alessandra , Johnson Anthony R , Yates Deborah H
Published: September 2008

Asbestos-related diffuse pleural thickening (DPT), or extensive fibrosis of the visceral pleura secondary to asbestos exposure, is increasingly common due to the large number of workers previously exposed to asbestos. It may coexist with asbestos related pleural plaques but has a distinctly different pathology. The pathogenesis of this condition as distinct from pleural plaques is gradually becoming understood. Generation of reactive oxygen and nitrogen species, profibrotic cytokines and growth factors in response to asbestos is likely to play a role in the formation of a fibrinous intrapleural matrix. Benign asbestos related pleural effusions commonly antedate the development of diffuse pleural thickening. Environmental as well as occupational exposure to asbestos may also result in pleural fibrosis, particularly in geographic areas with naturally occurring asbestiform soil minerals. Pleural disorders may also occur after household exposure. High resolution computed tomography (CT) is more sensitive and specific than chest radiography for the diagnosis of diffuse pleural thickening, and several classification systems for asbestos-related disorders have been devised. Magnetic resonance imaging and fluorodeoxyglucose positron emission tomography (PET) scanning may be useful in distinguishing between DPT and malignant mesothelioma. DPT may be associated with symptoms such as dyspnoea and chest pain. It causes a restrictive defect on lung function and may rarely result in respiratory failure and death. Treatment is primarily supportive.
Rb and hematopoiesis: stem cells to anemia
Authors: Walkley Carl R , Sankaran Vijay G , Orkin Stuart H
Published: September 2008

The retinoblastoma protein, Rb, was one of the first tumor suppressor genes identified as a result of the familial syndrome retinoblastoma. In the period since its identification and cloning a large number of studies have described its role in various cellular processes. The application of conditional somatic mutation with lineage and temporally controlled gene deletion strategies, thus circumventing the lethality associated with germ-line deletion of Rb, have allowed for a reanalysis of the in vivo role of Rb. In the hematopoietic system, such approaches have led to new insights into stem cell biology and the role of the microenvironment in regulating hematopoietic stem cell fate. They have also clarified the role that Rb plays during erythropoiesis and defined a novel mechanism linking mitochondrial function to terminal cell cycle withdrawal. These studies have shed light on the in vivo role of Rb in the regulation of hematopoiesis and also prompt further analysis of the role that Rb plays in both the regulation of hematopoietic stem cells and the terminal differentiation of their progeny.
High-precision potential-field and gradient-component transformations and derivative computations using cubic B-splines
Authors: Wang Bingzhu , Krebes Edward S. , Ravat Dhananjay
Published: September 2008

Potential-field and gradient-component transformations and derivative computations are necessary for many techniques of data enhancement, direct interpretation, and inversion. We advance new unified formulas for fast interpolation, differentiation, and integration and propose flexible high-precision algorithms to perform 3D and 2D potential-field- and gradient component transformations and derivative computations in the space domain using cubic B-splines. The spline-based algorithms are applicable to uniform or nonuniform rectangular grids for the 3D case and to regular or irregular grids for the 2D case. The fast Fourier transform (FFT) techniques require uniform grid spacing. The spline-based horizontal-derivative computations can be done at any point in the computational domain, whereas the FFT methods use only grid points. Comparisons between spline and FFT techniques through two gravity-gradient examples and one magnetic example show that results computed with the spline technique agree better with the exact theoretical data than do results computed with the FFT technique.
Robust wavelet estimation and blind deconvolution of noisy surface seismics
Authors: van der Baan Mirko , Pham Dinh-Tuan
Published: September 2008

Robust blind deconvolution is a challenging problem, particularly if the bandwidth of the seismic wavelet is narrow to very narrow; that is, if the wavelet bandwidth is similar to its principal frequency. The main problem is to estimate the phase of the wavelet with sufficient accuracy. The mutual information rate is a general-purpose criterion to measure whiteness using statistics of all orders. We modified this criterion to measure robustly the amplitude and phase spectrum of the wavelet in the presence of noise. No minimum phase assumptions were made. After wavelet estimation, we obtained an optimal deconvolution output using Wiener filtering. The new procedure performs well, even for very band-limited data; and it produces frequency-dependent phase estimates.
Interleukin-6, Cortisol, and Depressive Symptoms in Ovarian Cancer Patients
Authors: Lutgendorf Susan K. , Weinrib Aliza Z. , Penedo Frank , Russell Daniel , DeGeest Koen , Costanzo Erin S. , Henderson Patrick J. , Sephton Sandra E. , Rohleder Nicolas , Lucci Joseph A. , Cole Steven , Sood Anil K. , Lubaroff David M.
Published: September 2008

Purpose

Inflammatory processes have been implicated in the pathogenesis of both depression and cancer. Links between depressive symptoms, interleukin-6 (IL-6), and cortisol dysregulation have been demonstrated in cancer patients, but vegetative versus affective components of depression have been minimally examined. The objective of the current study was to examine associations between IL-6, diurnal cortisol rhythms, and facets of depression in epithelial ovarian cancer patients.

Patients and Methods

Patients awaiting surgery for a pelvic mass suspected for ovarian cancer completed questionnaires, collected salivary samples for 3 days presurgery, and gave a presurgical blood sample. Ascites was obtained during surgery. IL-6 was measured by enzyme-linked immunosorbent assay and cortisol by a chemiluminescence immunoassay. The final sample included 112 invasive ovarian cancer patients (86 advanced stage, 26 early stage) and 25 patients with tumors of low malignant potential (LMP).

Results

Advanced-stage ovarian cancer patients demonstrated elevations in vegetative and affective depressive symptoms, plasma IL-6, and the cortisol area under the curve (AUC) compared with patients with LMP tumors (all P < .05). Among invasive ovarian cancer patients, greater vegetative depression was related to elevated IL-6 in plasma (P = .008) and ascites (P = .024), but affective depression was unrelated to IL-6. Elevations in total depression (P = .026) and vegetative depression (P = .005) were also related to higher evening cortisol levels. Plasma IL-6 was related to greater afternoon and evening cortisol and cortisol AUC (all P values < .005).

Conclusion

These results demonstrate significant relationships between IL-6, cortisol, and vegetative depression, and may have implications for treatment of depression in ovarian cancer patients.
Parents’ Views of Cancer-Directed Therapy for Children With No Realistic Chance for Cure
Authors: Mack Jennifer W. , Joffe Steven , Hilden Joanne M. , Watterson Jan , Moore Caron , Weeks Jane C. , Wolfe Joanne
Published: September 2008

Purpose

Previous literature suggests that parents often wish to continue cancer-directed therapy for their children with incurable cancer. We assessed parents’ experiences with treatment for their children with cancer and no realistic chance of cure.

Patients and Methods

We administered questionnaires to 141 parents of children with cancer who died after receiving care at one of two cancer centers. Parents were asked whether the child benefited and suffered from treatment administered after the parent recognized that cure was not a realistic expectation, and whether they would recommend cancer-directed therapy to other families of children with advanced cancer.

Results

Fifty-three (38%) of 141 children received cancer-directed therapy after the parent recognized that the child had no realistic chance for cure. Most of these parents felt that their child had experienced at least some suffering resulting from the therapy (61%, 31 of 51) and little to no benefit (57%, 29 of 51). Fifty-one (38%) of 135 parents overall would recommend standard chemotherapy and 46 (33%) of 140 would recommend experimental chemotherapy to families of children with advanced cancer. Even parents who would not recommend standard chemotherapy generally felt the physician should offer it (91%, 88 of 97). Parents who reported that their children experienced suffering resulting from cancer-directed therapy (odds ratio = 0.46; P = .02) were less likely to recommend standard chemotherapy to other families.

Conclusion

Although many parents choose treatment for their children with incurable cancer, bereaved parents often would not recommend such therapy. Parents who felt their children suffered as a result of cancer treatment were particularly unlikely to recommend it.
Lower Osteopontin Plasma Levels Are Associated With Superior Outcomes in Advanced Non–Small-Cell Lung Cancer Patients Receiving Platinum-Based Chemotherapy: SWOG Study S0003
Authors: Mack Philip C. , Redman Mary W. , Chansky Kari , Williamson Stephen K. , Farneth Nichole C. , Lara Primo N. , Franklin Wilbur A. , Le Quynh-Thu , Crowley John J. , Gandara David R.
Published: September 2008

Purpose

S0003 was a phase III trial of carboplatin/paclitaxel with or without the hypoxic cytotoxin tirapazamine in patients with advanced or metastatic non–small-cell lung cancer (NSCLC). We investigated the relationship between clinical outcomes and plasma levels of the hypoxia-associated protein osteopontin (OPN) in patients on this protocol.

Patients and Methods

Baseline plasma was obtained from 172 patients. In 56 patients, sequential plasma was obtained after one or two cycles. Concentrations of OPN, as well as plasminogen activator inhibitor-1 (PAI-1) and vascular endothelial growth factor (VEGF), were measured using enzyme-linked immunosorbent assay. Tumor expression of OPN was assessed by immunohistochemistry in 61 matched archival specimens.

Results

Patients with lower OPN levels (below the median) had a significantly superior overall survival compared with patients with higher levels, regardless of treatment arm (hazard ratio [HR] = 0.60, P = .002). A similar correlation was observed for progression-free survival (HR = 0.69, P = .02). When examined as a continuous variable, OPN maintained its significant association with both progression-free (HR = 1.05, P = .01) and overall survival (HR = 1.09, P < .0001). Patients with lower plasma OPN levels were significantly more likely to have tumor response (P = .03). No differences were observed between treatment arms. Tumor OPN levels did not correlate with patient outcomes or with plasma levels. No associations were observed between patient outcomes and VEGF or PAI-1 levels; however, plasma concentrations of these markers were significantly interrelated (P < .0001) and significantly decreased after treatment (P = .0002 and P = .03, respectively).

Conclusion

Pretreatment plasma levels of OPN are significantly associated with patient response, progression-free survival, and overall survival in chemotherapy-treated patients with advanced NSCLC.
Analysis of piston assembly friction using the indicated mean effective pressure experimental method to validate mathematical models
Authors: Mufti R A , Priest M , Chittenden R J
Published: September 2008

The piston assembly friction is experimentally measured using the indicated mean effective pressure with detailed accuracy. The experimental results are compared with a relatively less complex piston assembly friction model typical of those used in industry, predicting the individual performance of compression rings, the oil control ring, and the piston skirt. The validation is carried out under fired conditions on a single-cylinder gasoline engine. The experimental results for an SAE 0W20 lubricant without a friction modifier were compared with the predictions. The predicted results correlate very well with the measurements, especially at higher lubricant inlet temperatures. The piston skirt friction was predicted using a simple concentric piston—cylinder model and a more realistic but computationally intensive method incorporating the piston's secondary motion. The results clearly indicate that a relatively less complex model can give realistic results under real engine conditions.
Diesel engine variable-geometry turbine turbocharger controlled by a multi-agent-based algorithm
Authors: Mastrovito M , Gaballo L , Dambrosio L
Published: September 2008

This paper provides an innovative technique for the control of a variable-geometry turbine in a turbocharged compression ignition engine. Such a control algorithm is based on a multi-agent System scheme. It is seldom that agents are considered as stand-alone systems; on the contrary, their main strength can be found in the interaction with other agents, constituting the so-called multi-agent System. An agent is a software or hardware entity that can receive signals from the environment and act upon that environment through output signals, trying to carry out an appropriate task. In the present paper, a fuzzy logic system has been employed for the agents' internal structure. In order to test the performance of the proposed control technique, a numerical model of the engine has been used, which employs a thermodynamic (zero-dimensional) approach. The paper will show that the proposed control technique is able to take into account the non-linearity of the controlled system.
Design of a networked traction control system using a real-time operating system
Authors: Shin Minsuk , Han Jaehyun , Youn Jeamyoung , Sunwoo Myoungho
Published: September 2008

In this paper, a design procedure is proposed for networked control systems (NCSs) using an embedded real-time operating system (RTOS). In a conventional design of NCSs, well-designed control algorithms do not result in the intended control performance after an implementation because of time delays, such as network-induced delays and controller computation delays. The proposed design procedure shows how to minimize the degradation of the control performance caused by the time delays. A performance index (PI) is derived from the difference between the performance of a simulated system and the performance of an implemented system with time delays. By using the proposed PI, optimized periods and priorities of tasks and communication messages of NCSs were determined. The design procedure was verified by designing a networked traction control system (TCS) using a real-time operating system for automotive electronics, OSEK-OS. The designed TCS was realized and tested by using a rapid control prototyping platform and a hardware-in-the-loop simulation environment.
Optimum design of an automotive inner door panel with a tailor-welded blank structure
Authors: Zhu P , Shi Y-L , Zhang K-Z , Lin Z-Q
Published: September 2008

This paper defines an integrated approach using finite element analysis, an artificial neural network (ANN), and a genetic algorithm (GA) for the optimization design of an inner door panel with a tailor-welded blank (TWB) structure, aiming at reducing the weight and enhancing the crashworthiness performances in side-impact collisions. In addition, strength and deformation resistance of the inner door panel are taken into account in the form of constraints in the optimization. First the governing equation of the central processing unit calculation time and the meshing method using the transition region is presented prior to the optimization process. Thus the dimension of the crash model can be controlled efficiently to prepare a fast-speed finite element model required for the later optimization. Then, in the initial design stage, a rough profile of the TWB structure is determined according to the distributions of the removed reinforcements around the inner door panel. Finally, the detailed design combines the ANN and the GA properly to provide an optimal combination of variables selected in the complicated multi-disciplinary problem. The optimal results indicate that the design framework presented here is outstanding with respect to the weight reduction and crashworthiness improvement.