bluuebunny/crossref_metadata_2025 huggingface dataset:
What is the optimal management option for occupational asthma?
Authors: Vandenplas Olivier , Dressel Holger , Nowak Dennis , Jamart Jacques
Published: June 2012

The optimal management of occupational asthma remains uncertain in clinical practice. The aim of this review was to analyse the published information pertaining to the management of occupational asthma in order to produce evidence-based statements and recommendations.

A systematic literature search was conducted up to March 2010 to identify original studies addressing the following different treatment options: 1) persistence of exposure; 2) pharmacological treatment; 3) complete avoidance of exposure; 4) reduction of exposure; and 5) the use of personal protective equipment.

After full text evaluation of 83 potentially relevant articles, 52 studies were retained for analysis.

The conclusions from this systematic review are limited by the methodological weaknesses of most published studies. Critical analysis of available evidence indicates that: 1) persistent exposure to the causal agent is more likely to result in asthma worsening than complete avoidance; 2) there is insufficient evidence to determine whether pharmacological treatment can alter the course of asthma in subjects who remain exposed; 3) avoidance of exposure leads to recovery of asthma in less than one-third of affected workers; 4) reduction of exposure seems to be less beneficial than complete avoidance of exposure; and 5) personal respiratory equipment does not provide complete protection.
What are the benefits of medical screening and surveillance?
Authors: Wilken Dennis , Baur Xaver , Barbinova Lioubov , Preisser Alexandra , Meijer Evert , Rooyackers Jos , Heederik Dick
Published: June 2012

Pre-employment examination is considered to be an important practice and is commonly performed in several countries within the European Union. The benefits of medical surveillance programmes are not generally accepted and their structure is often inconsistent.

The aim of this review was to evaluate, on the basis of the available literature, the usefulness of medical screening and surveillance. MEDLINE was searched from its inception up to March 2010. Retrieved literature was evaluated in a peer-review process and relevant data was collected following a systematic extraction schema.

Pre-placement screening identifies subjects who are at an increased risk for developing work-related allergic disease, but pre-employment screening is too low to be used as exclusion criteria. Medical surveillance programmes can identify workers who have, or who are developing, work-related asthma. These programmes can also be used to avoid worsening of symptoms by implementing preventive measures. A combination of different tools within the surveillance programme, adjusted for the risk of the individual worker, improves the predictive value.

Medical surveillance programmes provide medical as well as socioeconomic benefits. However, pre-employment screening cannot be used to exclude workers. They may act as a starting point for surveillance strategies. A stratified approach can increase the effectiveness and reduce the costs for such programmes.
Comparing thousands of circular genomes using the CGView Comparison Tool
Authors: Grant Jason R , Arantes Adriano S , Stothard Paul
Published: June 2012

Background

Continued sequencing efforts coupled with advances in sequencing technology will lead to the completion of a vast number of small genomes. Whole-genome comparisons represent an important part of the analysis of any new genome sequence, as they can provide a better understanding of the biology and evolution of the source organism. Visualization of the results is important, as it allows information from a variety of sources to be integrated and interpreted. However, existing graphical comparison tools lack features needed for efficiently comparing a new genome to hundreds or thousands of existing sequences. Moreover, existing tools are limited in terms of the types of comparisons that can be performed, the extent to which the output can be customized, and the ease with which the entire process can be automated.

Results

The CGView Comparison Tool (CCT) is a package for visually comparing bacterial, plasmid, chloroplast, or mitochondrial sequences of interest to existing genomes or sequence collections. The comparisons are conducted using BLAST, and the BLAST results are presented in the form of graphical maps that can also show sequence features, gene and protein names, COG (Clusters of Orthologous Groups of proteins) category assignments, and sequence composition characteristics. CCT can generate maps in a variety of sizes, including 400 Megapixel maps suitable for posters. Comparisons can be conducted within a particular species or genus, or all available genomes can be used. The entire map creation process, from downloading sequences to redrawing zoomed maps, can be completed easily using scripts included with the CCT. User-defined features or analysis results can be included on maps, and maps can be extensively customized. To simplify program setup, a CCT virtual machine that includes all dependencies preinstalled is available. Detailed tutorials illustrating the use of CCT are included with the CCT documentation.

Conclusion

CCT can be used to visually compare a reference sequence to thousands of existing genomes or sequence collections (next-generation sequencing reads for example) on a standard desktop computer. It provides analysis and visualization functionality not available in any existing circular genome visualization tool. By visually presenting sequence conservation information along with functional classifications and sequence composition characteristics, CCT can be a useful tool for identifying rapidly evolving or novel sequences, horizontally transferred sequences, or unusual functional properties in newly sequenced genomes. CCT is freely available for download at http://stothard.afns.ualberta.ca/downloads/CCT/.
Multi-locus variable number tandem repeat analysis of 7th pandemic Vibrio cholerae
Authors: Lam Connie , Octavia Sophie , Reeves Peter R , Lan Ruiting
Published: June 2012

Background

Seven pandemics of cholera have been recorded since 1817, with the current and ongoing pandemic affecting almost every continent. Cholera remains endemic in developing countries and is still a significant public health issue. In this study we use multilocus variable number of tandem repeats (VNTRs) analysis (MLVA) to discriminate between isolates of the 7th pandemic clone of Vibrio cholerae.

Results

MLVA of six VNTRs selected from previously published data distinguished 66 V. cholerae isolates collected between 1961–1999 into 60 unique MLVA profiles. Only 4 MLVA profiles consisted of more than 2 isolates. The discriminatory power was 0.995. Phylogenetic analysis showed that, except for the closely related profiles, the relationships derived from MLVA profiles were in conflict with that inferred from Single Nucleotide Polymorphism (SNP) typing. The six SNP groups share consensus VNTR patterns and two SNP groups contained isolates which differed by only one VNTR locus.

Conclusions

MLVA is highly discriminatory in differentiating 7th pandemic V. cholerae isolates and MLVA data was most useful in resolving the genetic relationships among isolates within groups previously defined by SNPs. Thus MLVA is best used in conjunction with SNP typing in order to best determine the evolutionary relationships among the 7th pandemic V. cholerae isolates and for longer term epidemiological typing.
Association between polymorphisms in the adiponectin gene and cardiovascular disease: a meta-analysis
Authors: Zhang Huan , Mo Xingbo , Hao Yongchen , Gu Dongfeng
Published: June 2012

Background

Previous studies have examined the associations between polymorphisms of adiponectin gene (ADIPOQ) and cardiovascular disease (CVD), but those studies have been inconclusive. The aim of this study was to access the relationship between three single nucleotide polymorphisms (SNPs), +45 T > G (rs2241766), +276 G > T (rs1501299) and -11377 C > G (rs266729) in ADIPOQ and CVD.

Methods

A comprehensive search was conducted to identify all studies on the association of ADIPOQ gene polymorphisms with CVD risk. The fixed and random effect pooled measures (i.e. odds ratio (OR) and 95% confidence interval (CI)) were calculated in the meta-analysis. Heterogeneity among studies was evaluated using Q test and the I2. Publication bias was estimated using modified Egger’s linear regression test.

Results

Thirty-seven studies concerning the associations between the three polymorphisms of ADIPOQ gene and CVD risk were enrolled in this meta-analysis, including 6,398 cases and 10,829 controls for rs2241766, 8,392 cases and 18,730 controls for rs1501299 and 7,835 cases and 14,023 controls for rs266729. The three SNPs were significantly associated with CVD, yielding pooled ORs of 1.22 (95%CI: 1.07, 1.39; P = 0.004), 0.90 (95%CI: 0.83, 0.97; P = 0.007) and 1.09(95%CI: 1.01, 1.17; P = 0.032) for rs2241766, rs1501299 and rs266729, respectively. Rs2241766 and rs1501299 were significantly associated with coronary heart disease (CHD), yielding pooled ORs of 1.29 (95%CI: 1.09, 1.52; P = 0.004) and 0.89 (95%CI: 0.81, 0.99; P = 0.025), respectively. The pooled OR for rs266729 and CHD was 1.09 (95%CI: 0.99, 1.19; P = 0.090). Significant between-study heterogeneity was found in our meta-analysis. Evidence of publication bias was observed in the meta-analysis.

Conclusions

The present meta-analysis showed that the associations between rs2241766, rs1501299 and rs266729 in the ADIPOQ and CVD were significant but weak. High quality studies are still needed to confirm the associations, especially for rs2241766.
Barriers to condom use among women at risk of HIV/AIDS: a qualitative study from Iran
Authors: Lotfi Razieh , Tehrani Fahimeh Ramezani , Yaghmaei Farideh , Hajizadeh Ebrahim
Published: June 2012

Background

The growing trend of women infected with HIV through sexual transmission is alarming. Factors influencing condom use have not yet been fully identified, especially in countries with conservative cultures and backgrounds. The present study aimed to explore the barriers of condom use in Iranian women at risk of HIV.

Methods

Using the grounded theory methodology, participants’ experiences and their perceptions regarding condom were collected during semi structured in depth interviews. Participants were 22 women, aged 21–49 years, considered to be at risk for HIV, due to their own or their partner’s sexual behaviors. Qualitative analysis of the data was conducted manually and was guided by constant comparative analysis.

Results

Two main barriers, personal and socio-environmental emerged from data analysis. Lack of perceived threat, absence of protective motivation, inadequate knowledge, perceived lack of control, negative attitudes towards condom and misperception were the major personal barriers, while unsupportive environments and cultural norms were the common socio-environmental barriers to condom use among these at risk women.

Conclusions

These critical barriers have to be addressed for implementing effective prevention programs against HIV among populations at risk for HIV.
The effect of yoga on women with secondary arm lymphoedema from breast cancer treatment
Authors: Loudon Annette , Barnett Tony , Piller Neil , Immink Maarten A , Visentin Denis , Williams Andrew D
Published: June 2012

Background

Women who develop secondary arm lymphoedema subsequent to treatment associated with breast cancer require life-long management for a range of symptoms including arm swelling, heaviness, tightness in the arm and sometimes the chest, upper body impairment and changes to a range of parameters relating to quality of life. While exercise under controlled conditions has had positive outcomes, the impact of yoga has not been investigated. The aim of this study is to determine the effectiveness of yoga in the physical and psycho-social domains, in the hope that women can be offered another safe, holistic modality to help control many, if not all, of the effects of secondary arm lymphoedema.

Methods and design

A randomised controlled pilot trial will be conducted in Hobart and Launceston with a total of 40 women receiving either yoga intervention or current best practice care. Intervention will consist of eight weeks of a weekly teacher-led yoga class with a home-based daily yoga practice delivered by DVD. Primary outcome measures will be the effects of yoga on lymphoedema and its associated symptoms and quality of life. Secondary outcome measures will be range of motion of the arm and thoracic spine, shoulder strength, and weekly and daily physical activity. Primary and secondary outcomes will be measured at baseline, weeks four, eight and a four week follow up at week twelve. Range of motion of the spine, in a self-nominated group, will be measured at baseline, weeks eight and twelve. A further outcome will be the women’s perceptions of the yoga collected by interview at week eight.

Discussion

The results of this trial will provide information on the safety and effectiveness of yoga for women with secondary arm lymphoedema from breast cancer treatment. It will also inform methodology for future, larger trials.

Trial registration

ACTRN12611000202965
An electronic health record-enabled obesity database
Authors: Wood G Craig , Chu Xin , Manney Christina , Strodel William , Petrick Anthony , Gabrielsen Jon , Seiler Jamie , Carey David , Argyropoulos George , Benotti Peter , Still Christopher D , Gerhard Glenn S
Published: June 2012

Background

The effectiveness of weight loss therapies is commonly measured using body mass index and other obesity-related variables. Although these data are often stored in electronic health records (EHRs) and potentially very accessible, few studies on obesity and weight loss have used data derived from EHRs. We developed processes for obtaining data from the EHR in order to construct a database on patients undergoing Roux-en-Y gastric bypass (RYGB) surgery.

Methods

Clinical data obtained as part of standard of care in a bariatric surgery program at an integrated health delivery system were extracted from the EHR and deposited into a data warehouse. Data files were extracted, cleaned, and stored in research datasets. To illustrate the utility of the data, Kaplan-Meier analysis was used to estimate length of post-operative follow-up.

Results

Demographic, laboratory, medication, co-morbidity, and survey data were obtained from 2028 patients who had undergone RYGB at the same institution since 2004. Pre-and post-operative diagnostic and prescribing information were available on all patients, while survey laboratory data were available on a majority of patients. The number of patients with post-operative laboratory test results varied by test. Based on Kaplan-Meier estimates, over 74% of patients had post-operative weight data available at 4 years.

Conclusion

A variety of EHR-derived data related to obesity can be efficiently obtained and used to study important outcomes following RYGB.
What is preventable harm in healthcare? A systematic review of definitions
Authors: Nabhan Mohammed , Elraiyah Tarig , Brown Daniel R , Dilling James , LeBlanc Annie , Montori Victor M , Morgenthaler Timothy , Naessens James , Prokop Larry , Roger Veronique , Swensen Stephen , Thompson Rodney L , Murad M Hassan
Published: June 2012

Background

Mitigating or reducing the risk of harm associated with the delivery of healthcare is a policy priority. While the risk of harm can be reduced in some instances (i.e. preventable), what constitutes preventable harm remains unclear. A standardized and clear definition of preventable harm is the first step towards safer and more efficient healthcare delivery system. We aimed to summarize the definitions of preventable harm and its conceptualization in healthcare.

Methods

We conducted a comprehensive electronic search of relevant databases from January 2001 to June 2011 for publications that reported a definition of preventable harm. Only English language publications were included. Definitions were coded for common concepts and themes. We included any study type, both original studies and reviews. Two reviewers screened the references for eligibility and 28% (127/460) were finally included. Data collected from studies included study type, description of the study population and setting, and data corresponding to the outcome of interest. Three reviewers extracted the data. The level of agreement between the reviewers was calculated.

Results

One hundred and twenty seven studies were eligible. The three most prevalent preventable harms in the included studies were: medication adverse events (33/127 studies, 26%), central line infections (7/127, 6%) and venous thromboembolism (5/127, 4%). Seven themes or definitions for preventable harm were encountered. The top three were: presence of an identifiable modifiable cause (58/132 definitions, 44%), reasonable adaptation to a process will prevent future recurrence (30/132, 23%), adherence to guidelines (22/132, 16%). Data on the validity or operational characteristic (e.g., accuracy, reproducibility) of definitions were limited.

Conclusions

There is limited empirical evidence of the validity and reliability of the available definitions of preventable harm, such that no single one is supported by high quality evidence. The most common definition is “presence of an identifiable, modifiable cause of harm”.
Extracellular cyclophilin-A stimulates ERK1/2 phosphorylation in a cell-dependent manner but broadly stimulates nuclear factor kappa B
Authors: Bahmed Karim , Henry Curtis , Holliday Michael , Redzic Jasmina , Ciobanu Madalina , Zhang Fengli , Weekes Colin , Sclafani Robert , DeGregori James , Eisenmesser Elan
Published: June 2012

Background

Although the peptidyl-prolyl isomerase, cyclophilin-A (peptidyl-prolyl isomerase, PPIA), has been studied for decades in the context of its intracellular functions, its extracellular roles as a major contributor to both inflammation and multiple cancers have more recently emerged. A wide range of activities have been ascribed to extracellular PPIA that include induction of cytokine and matrix metalloproteinase (MMP) secretion, which potentially underlie its roles in inflammation and tumorigenesis. However, there have been conflicting reports as to which particular signaling events are under extracellular PPIA regulation, which may be due to either cell-dependent responses and/or the use of commercial preparations recently shown to be highly impure.

Methods

We have produced and validated the purity of recombinant PPIA in order to subject it to a comparative analysis between different cell types. Specifically, we have used a combination of multiple methods such as luciferase reporter screens, translocation assays, phosphorylation assays, and nuclear magnetic resonance to compare extracellular PPIA activities in several different cell lines that included epithelial and monocytic cells.

Results

Our findings have revealed that extracellular PPIA activity is cell type-dependent and that PPIA signals via multiple cellular receptors beyond the single transmembrane receptor previously identified, Extracellular Matrix MetalloPRoteinase Inducer (EMMPRIN). Finally, while our studies provide important insight into the cell-specific responses, they also indicate that there are consistent responses such as nuclear factor kappa B (NFκB) signaling induced in all cell lines tested.

Conclusions

We conclude that although extracellular PPIA activates several common pathways, it also targets different receptors in different cell types, resulting in a complex, integrated signaling network that is cell type-specific.
Proteomic identification of host and parasite biomarkers in saliva from patients with uncomplicated Plasmodium falciparum malaria
Authors: Huang Honglei , Mackeen Mukram M , Cook Matthew , Oriero Eniyou , Locke Emily , Thézénas Marie L , Kessler Benedikt M , Nwakanma Davis , Casals-Pascual Climent
Published: June 2012

Background

Malaria cases attributed toPlasmodium falciparumaccount for approximately 600,000 deaths yearly, mainly in African children. The gold standard method to diagnose malaria requires the visualization of the parasite in blood. The role of non-invasive diagnostic methods to diagnose malaria remains unclear.

Methods

A protocol was optimized to deplete highly abundant proteins from saliva to improve the dynamic range of the proteins identified and assess their suitability as candidate biomarkers of malaria infection. A starch-based amylase depletion strategy was used in combination with four different lectins to deplete glycoproteins (Concanavalin A andAleuria aurantiaforN-linked glycoproteins; jacalin and peanut agglutinin forO-linked glycoproteins). A proteomic analysis of depleted saliva samples was performed in 17 children with fever and a positive–malaria slide and compared with that of 17 malaria-negative children with fever.

Results

The proteomic signature of malaria-positive patients revealed a strong up-regulation of erythrocyte-derived and inflammatory proteins. ThreeP. falciparumproteins, PFL0480w, PF08_0054 and PFI0875w, were identified in malaria patients and not in controls.Aleuria aurantiaand jacalin showed the best results for parasite protein identification.

Conclusions

This study shows that saliva is a suitable clinical specimen for biomarker discovery. Parasite proteins and several potential biomarkers were identified in patients with malaria but not in patients with other causes of fever. The diagnostic performance of these markers should be addressed prospectively.
Equity in public health standards: a qualitative document analysis of policies from two Canadian provinces
Authors: Pinto Andrew D , Manson Heather , Pauly Bernadette , Thanos Joanne , Parks Amanda , Cox Amy
Published: June 2012

Introduction

Promoting health equity is a key goal of many public health systems. However, little is known about how equity is conceptualized in such systems, particularly as standards of public health practice are established. As part of a larger study examining the renewal of public health in two Canadian provinces, Ontario and British Columbia (BC), we undertook an analysis of relevant public health documents related to equity. The aim of this paper is to discuss how equity is considered within documents that outline standards for public health.

Methods

A research team consisting of policymakers and academics identified key documents related to the public health renewal process in each province. The documents were analyzed using constant comparative analysis to identify key themes related to the conceptualization and integration of health equity as part of public health renewal in Ontario and BC. Documents were coded inductively with higher levels of abstraction achieved through multiple readings. Sets of questions were developed to guide the analysis throughout the process.

Results

In both sets of provincial documents health inequities were defined in a similar fashion, as the consequence of unfair or unjust structural conditions. Reducing health inequities was an explicit goal of the public health renewal process. In Ontario, addressing “priority populations” was used as a proxy term for health equity and the focus was on existing programs. In BC, the incorporation of an equity lens enhanced the identification of health inequities, with a particular emphasis on the social determinants of health. In both, priority was given to reducing barriers to public health services and to forming partnerships with other sectors to reduce health inequities. Limits to the accountability of public health to reduce health inequities were identified in both provinces.

Conclusion

This study contributes to understanding how health equity is conceptualized and incorporated into standards for local public health. As reflected in their policies, both provinces have embraced the importance of reducing health inequities. Both concepualized this process as rooted in structural injustices and the social determinants of health. Differences in the conceptualization of health equity likely reflect contextual influences on the public health renewal processes in each jurisdiction.
Genetic characterization of Chikungunya virus from New Delhi reveal emergence of a new molecular signature in Indian isolates
Authors: Shrinet Jatin , Jain Shanu , Sharma Anil , Singh Shashi Shekhar , Mathur Kalika , Rana Vandita , Bhatnagar Raj K , Gupta Bhupendra , Gaind Rajni , Deb Monorama , Sunil Sujatha
Published: June 2012

Background

Chikungunya (CHIK) is currently endemic in South and Central India and exist as co-infections with dengue in Northern India. In 2010, New Delhi witnessed an outbreak of CHIK in the months October-December. This was the first incidence of a dominant CHIK outbreak in Delhi and prompted us to characterize the Delhi virus strains. We have also investigated the evolution of CHIK spread in India.

Findings

Clinical samples were subjected to RT-PCR to detect CHIK viral RNA. The PCR amplified products were sequenced and the resulting sequences were genetically analyzed. Phylogenetic analysis based on partial sequences of the structural proteins E1 and E2 revealed that the viruses in the latest outbreak exhibited ECSA lineage. Two novel mutations, E1 K211E and E2 V264A were observed in all Delhi isolates. In addition, CHIKV sequences from eight states in India were analyzed along with Delhi sequences to map the genetic diversity of CHIKV within the country. Estimates of average evolutionary divergence within states showed varying divergence among the sequences both within the states and between the states. We identified distinct molecular signatures of the different genotypes of CHIKV revealing emergence of a new signature in the New Delhi clade. Statistical analyses and construction of evolutionary path of the virus within the country revealed gradual spread of one specific strain all over the country.

Conclusion

This study has identified unique mutations in the E1 and E2 genes and has revealed the presence of ancestral CHIKV population with maximum diversity circulating in Maharashtra. The study has further revealed the trend of CHIK spread in India since its first report in 1963 and its subsequent reappearance in 2005.
Nano-titanium dioxide modulates the dermal sensitization potency of DNCB
Authors: Hussain Salik , Smulders Stijn , De Vooght Vanessa , Ectors Bert , Boland Sonja , Marano Francelyne , Van Landuyt Kirsten L , Nemery Benoit , Hoet Peter HM , Vanoirbeek Jeroen AJ
Published: June 2012

We determined the ability of a model nanoparticle (NP) (titanium dioxide, TiO2) to modulate sensitization induced by a known potent dermal sensitizer (dinitrochlorobenzene) using a variant of the local lymph node assay called lymph node proliferation assay.

BALB/c mice received sub-cutaneous injections of vehicle (2.5 mM sodium citrate), TiO2NPs (0.004, 0.04 or 0.4 mg/ml) or pigment particles (0.04 mg/ml) both stabilized in sodium citrate buffer at the base of each ear (2x50μl), before receiving dermal applications (on both ears) of 2,4-Dinitrochlorobenzene (DNCB) (2x25μl of 0.1%) or its vehicle (acetone olive oil – AOO (4:1)) on days 0, 1 and 2. On day 5, the stimulation index (SI) was calculated as a ratio of3HTdR incorporation in lymphocytes from DNBC-treated mice and AOO-treated controls. In a second experiment the EC3-value for DNCB (0 to 0.1%) was assessed in the absence or presence of 0.04 mg/ml TiO2. In a third experiment, the lymphocyte subpopulations and the cytokine secretion profile were analyzed after TiO2(0.04 mg/ml) and DNCB (0.1%) treatment.

Injection of NPs in AOO-treated control mice did not have any effect on lymph node (LN) proliferation. DNCB sensitization resulted in LN proliferation, which was further increased by injection of TiO2NPs before DNCB sensitization. The EC3of DNCB, with prior injection of vehicle control was 0.041%, while injection with TiO2decreased the EC3of DNCB to 0.015%. TiO2NPs pre-treatment did not alter the lymphocyte subpopulations, but significantly increased the level of IL-4 and decreased IL-10 production in DNCB treated animals.

In conclusion, our study demonstrates that administration of nano-TiO2increases the dermal sensitization potency of DNCB, by augmenting a Th2response, showing the immunomodulatory abilities of NPs.
Evaluation of expression and function of vascular endothelial growth factor receptor 2, platelet derived growth factor receptors-alpha and -beta, KIT, and RET in canine apocrine gland anal sac adenocarcinoma and thyroid carcinoma
Authors: Urie Bridget K , Russell Duncan S , Kisseberth William C , London Cheryl A
Published: June 2012

Background

Toceranib phosphate (Palladia) has a reported objective response rate of 25% in both canine apocrine gland anal sac adenocarcinoma (AGASACA) and thyroid carcinoma (TC), with stable disease occurring in an additional 50-60% of dogs. The basis for the observed responses to toceranib is not known. The purpose of this study was to evaluate AGASACA and TC samples for the expression and activation of VEGFR2, PDGFRα, PDGFRβ, KIT and RET to assess whether dysregulation of these receptor tyrosine kinases (RTKs) may contribute to the biologic activity of toceranib.

Results

mRNA for VEGFR2, PDGFRα/β, KIT and RET was detected in all AGASACA samples. mRNA for VEGFR2, PDGFRα/β, and KIT was detected in all TC samples, while mRNA for RET was amplified in 10/15 samples. No phosphorylation of VEGFR2, PDGFRα/β, or KIT was observed on the arrays. However, phosphorylation of RET was detected in 54% of the primary AGASACA and 20% of TC. VEGFR2 was expressed in 19/24 primary and 6/10 metastatic AGASACA and 6/15 TC samples. KIT was present in 8/24 primary and 3/10 metastatic AGASACA and 9/15 TC samples. PDGFRα expression was noted in all tumor samples. In contrast PDGFRβ expression was found in only a few tumor samples but was evident in the stroma of all tumor specimens.

Conclusions

Known targets of toceranib are expressed in both AGASAC and TC. Given the observed expression of VEGFR and PDGFRα/β and phosphorylation of RET, these RTKs merit investigation as to their roles in the biology of AGSACA and TC and their contribution to toceranib’s activity.
Structural evaluation of sugar cane bagasse steam pretreated in the presence of CO2 and SO2
Authors: Corrales Roberta Cristina Novaes Reis , Mendes Fabiana Magalhães Teixeira , Perrone Clarissa Cruz , Sant’Anna Celso , de Souza Wanderley , Abud Yuri , Bon Elba Pinto Pinto da Silva , Ferreira-Leitão Viridiana
Published: June 2012

Background

Previous studies on the use of SO2 and CO2 as impregnating agent for sugar cane bagasse steam treatment showed comparative and promising results concerning the cellulose enzymatic hydrolysis and the low formation of the inhibitors furfural and hydroxymethylfurfural for the use of CO2 at 205°C/15 min or SO2 at 190°C/5 min. In the present study sugar cane bagasse materials pretreated as aforementioned were analyzed by scanning and transmission electron microscopy (SEM and TEM), X-Ray Diffraction (XRD) and Infrared (FTIR spectroscopy) aiming a better understanding of the structural and chemical changes undergone by the pretreated materials.

Results

SEM and TEM data showed that the structural modifications undergone by the pretreatment with CO2 were less pronounced in comparison to that using SO2, which can be directly related to the combined severity of each pretreatment. According to XRD data, untreated bagasse showed, as expected, a lower crystallinity index (CI = 48.0%) when compared to pretreated samples with SO2 (CI = 65.5%) or CO2 (CI = 56.4%), due to the hemicellulose removal of 68.3% and 40.5%, respectively. FTIR spectroscopy supported SEM, TEM and XRD results, revealing a more extensive action of SO2.

Conclusions

The SEM, TEM, XRD and FTIR spectroscopy techniques used in this work contributed to structural and chemical analysis of the untreated and pretreated bagasse. The images from SEM and TEM can be related to the severity of SO2 pretreatment, which is almost twice higher. The crystallinity index values obtained from XRD showed that pretreated materials have higher values when compared with untreated material, due to the partial removal of hemicellulose after pretreatment. FTIR spectroscopy supported SEM, TEM and XRD results. CO2 can actually be used as impregnating agent for steam pretreatment, although the present study confirmed a more extensive action of SO2.
N-acetylcysteine for the prevention of stricture after circumferential endoscopic submucosal dissection of the esophagus: a randomized trial in a porcine model
Authors: Barret Maximilien , Batteux Frédéric , Beuvon Frédéric , Mangialavori Luigi , Chryssostalis Ariane , Pratico Carlos , Chaussade Stanislas , Prat Frédéric
Published: June 2012

Background

Circumferential endoscopic submucosal dissection (CESD) of the esophagus would allow for both the eradication of Barrett’s esophagus and its related complications, such as advanced neoplasia. However, such procedures generally induce inflammatory repair resulting in a fibrotic stricture. N-acetylcysteine (NAC) is an antioxidant that has shown some efficacy against pulmonary and hepatic fibrosis. The aim of our study was to evaluate the benefit of NAC in the prevention of esophageal cicatricial stricture after CESD in a swine model.

Animals and methods

Two groups of six pigs each were subjected to general anesthesia and CESD: after randomization, a first group received an oral NAC treatment regimen of 100 mg/kg/day, initiated one week before the procedure, whereas a second group was followed without any prophylactic treatment. Follow-up endoscopies took place seven, fourteen, twenty-one, and twenty-eight days after CESD. Necropsy, histological assessment of esophageal inflammation, and fibrosis were performed on day 28.

Results

The median esophageal lumen diameter on day 21 (main judgment criterion) was 4 mm (range 2 to 5) in group 1 and 3 mm (range 1 to 7) in group 2 (P = 0.95). No significant difference was observed between the two groups regarding clinical evaluation (time before onset of clinically significant esophageal obstruction), number of dilations, esophageal inflammation and fibrosis, or oxidative stress damage on immunohistochemistry.

Conclusions

Despite its antioxidant effect, systemic administration of NAC did not show significant benefit on esophageal fibrosis in our animal model of esophageal wound healing within the experimental conditions of this study. Since the administered doses were relatively high, it seems unlikely that NAC might be a valuable option for the prevention of post-endoscopic esophageal stricture.
Sexually dimorphic effect of aging on skeletal muscle protein synthesis
Authors: Smith Gordon I , Reeds Dominic N , Hall Angela M , Chambers Kari T , Finck Brian N , Mittendorfer Bettina
Published: June 2012

Background

Although there appear to be no differences in muscle protein turnover in young and middle aged men and women, we have reported significant differences in the rate of muscle protein synthesis between older adult men and women. This suggests that aging may affect muscle protein turnover differently in men and women.

Methods

We measured the skeletal muscle protein fractional synthesis rate (FSR) by using stable isotope-labeled tracer methods during basal postabsorptive conditions and during a hyperaminoacidemic-hyperinsulinemic-euglycemic clamp in eight young men (25–45 y), ten young women (25–45 y), ten old men (65–85 y) and ten old women (65–85 y).

Results

The basal muscle protein FSR was not different in young and old men (0.040 ± 0.004 and 0.043 ± 0.005%·h-1, respectively) and combined insulin, glucose and amino acid infusion significantly increased the muscle protein FSR both in young (to 0.063 ± 0.006%·h-1) and old (to 0.051 ± 0.008%·h-1) men but the increase (0.023 ± 0.004 vs. 0.009 ± 0.004%·h-1, respectively) was ~60% less in the old men (P = 0.03). In contrast, the basal muscle protein FSR was ~30% greater in old than young women (0.060 ± 0.003 vs. 0.046 ± 0.004%·h-1, respectively; P < 0.05) and combined insulin, glucose and amino acid infusion significantly increased the muscle protein FSR in young (P < 0.01) but not in old women (P = 0.10) so that the FSR was not different between young and old women during the clamp (0.074 ± 0.006%·h-1 vs. 0.072 ± 0.006%·h-1, respectively).

Conclusions

There is sexual dimorphism in the age-related changes in muscle protein synthesis and thus the metabolic processes responsible for the age-related decline in muscle mass.
Microbiological safety of a novel bio-artificial liver support system based on porcine hepatocytes: a experimental study
Authors: Han Bing , Shi Xiao-lei , Zhang Yue , Chu Xue-hui , Gu Jin-yang , Xiao Jiang-qiang , Ren Hao-zhen , Tan Jia-jun , Gu Zhong-ze , Ding Yi-tao
Published: June 2012

Background

Our institute has developed a novel bio-artificial liver (BAL) support system, based on a multi-layer radial-flow bioreactor carrying porcine hepatocytes and mesenchymal stem cells. It has been shown that porcine hepatocytes are capable of carrying infectious porcine endogenous retroviruses (PERVs) into human cells, thus the microbiological safety of any such system must be confirmed before clinical trials can be performed. In this study, we focused on assessing the status of PERV infection in beagles treated with the novel BAL.

Methods

Five normal beagles were treated with the novel BAL for 6 hours. The study was conducted for 6 months, during which plasma was collected from the BAL and whole blood from the beagles at regular intervals. DNA and RNA in both the collected peripheral blood mononuclear cells (PBMCs) and plasma samples were extracted for conventional PCR and reverse transcriptase (RT)-PCR with PERV-specific primers and the porcine-specific primer Sus scrofa cytochrome B. Meanwhile, the RT activity and the in vitro infectivity of the plasma were measured.

Results

Positive PERV RNA and RT activity were detected only in the plasma samples taken from the third circuit of the BAL system. All other samples including PBMCs and other plasma samples were negative for PERV RNA, PERV DNA, and RT activity. In the in vitro infection experiment, no infection was found in HEK293 cells treated with plasma.

Conclusions

No infective PERV was detected in the experimental animals, thus the novel BAL had a reliable microbiological safety profile.
Analysis of wind speed data and wind energy potential in three selected locations in south-east Nigeria
Authors: Oyedepo Sunday O , Adaramola Muyiwa S , Paul Samuel S
Published: June 2012

In this study, the wind speed characteristics and energy potential in three selected locations in the southeastern part of Nigeria were investigated using wind speed data that span between 24 and 37 years and measured at a height of 10 m. It was shown that the annual mean wind speed at a height of 10 m for Enugu, Owerri and Onitsha are 5.42, 3.36 and 3.59 m/s, respectively, while the annual mean power densities are 96.98, 23.23 and 28.34 W/m2, respectively. It was further shown that the mean annual value of the most probable wind speed are 5.47, 3.72 and 3.50 m/s for Enugu, Owerri and Onitsha, respectively, while the respective annual value of the wind speed carrying maximum energy are 6.48, 4.33 and 3.90 m/s. The performance of selected commercial wind turbine models (with rated power between 50 and 1,000 kW) designed for electricity generation and a windmill (rated power, 0.36 kW) for water pumping located in these sites was examined. The annual energy output and capacity factor for these turbines, as well as the water produced by the windmill, were determined. The minimum required design parameters for a wind turbine to be a viable option for electricity generation in each location are also suggested.
Limited effect of anti-rheumatic treatment on 15-prostaglandin dehydrogenase in rheumatoid arthritis synovial tissue
Authors: Gheorghe Karina Roxana , Sadique Syed , Leclerc Patrick , Idborg Helena , Wobst Ivonne , Catrina Anca Irinel , Jakobsson Per-Johan , Korotkova Marina
Published: June 2012

Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory disease in which prostaglandin E2 (PGE2) displays an important pathogenic role. The enzymes involved in its synthesis are highly expressed in the inflamed synovium, while little is known about 15- prostaglandin dehydrogenase (15-PGDH) that metabolizes PGE2. Here we aimed to evaluate the localization of 15-PGDH in the synovial tissue of healthy individuals or patients with inflammatory arthritis and determine the influence of common RA therapy on its expression.

Methods

Synovial tissue specimens from healthy individuals, psoriatic arthritis, ostheoarthritis and RA patients were immunohistochemically stained to describe the expression pattern of 15-PGDH. In addition, the degree of enzyme staining was evaluated by computer analysis on stained synovial biopsies from two groups of RA patients, before and after RA specific treatment with either intra-articular glucocorticoids or oral methotrexate therapy. Prostaglandins derived from the cyclooxygenase (COX) pathway were determined by liquid-chromatography mass spectrometry in supernatants from interleukin (IL) 1β-activated fibroblast-like synoviocytes (FLS) treated with methotrexate.

Results

15-PGDH was present in healthy and inflamed synovial tissue, mainly in lining macrophages, fibroblasts and vessels. Intra-articular glucocorticoids showed a trend towards reduced 15-PGDH expression in RA synovium (p = 0.08) while methotrexate treatment left the PGE2 pathway unaltered both in biopsies ex vivo and in cultured FLS.

Conclusions

Early methotrexate therapy has little influence on the expression of 15-PGDH and on any of the PGE2 synthesizing enzymes or COX-derived metabolites. Thus therapeutic strategies involving blocking induced PGE2 synthesis may find a rationale in additionally reducing local inflammatory mediators.
Disruption of rhythms of molecular clocks in primary synovial fibroblasts of patients with osteoarthritis and rheumatoid arthritis, role of IL-1β/TNF
Authors: Haas Stefanie , Straub Rainer H
Published: June 2012

Introduction

Circadian rhythms play an important role in the body and in single cells. Rhythms of molecular clocks have not been investigated in synovial fibroblasts (SF) of patients with osteoarthritis (OA) and rheumatoid arthritis (RA). The study was initiated to fill this gap and to study effects of interleukin (IL)-1β/tumor necrosis factor (TNF) on rhythmicity in synovial fibroblasts of RA and OA patients.

Methods

The presence of BMAL-1, CLOCK, Period 1 and Period 2 proteins in synovial tissue was investigated by immunofluorescence. The presence of mRNA of molecular clocks was studied during 72 h by qPCR. Characteristics of rhythms were studied with time series analysis.

Results

BMAL-1, CLOCK, Period 1 and Period 2 proteins were abundantly present in synovial tissue of OA, RA and controls. Receiving synovial tissue at different operation time points during the day (8:00 am to 4:00 pm) did not reveal a rhythm of BMAL-1 or Period 1 protein. In OASF and RASF, no typical rhythm curve of molecular clock mRNA was observed. Time series analysis identified a first peak between 2 and 18 hours after synchronization but a period was not detectable due to loss of rhythm. TNF inhibited mRNA of CLOCK, Period 1 and Period 2 in OASF, while IL-1β and TNF increased these factors in RASF. This was supported by dose-dependently increased levels in MH7A RA fibroblasts. In RASF, IL-1β and TNF shifted the first peak of BMAL-1 mRNA to later time points (8 h to 14 h).

Conclusion

Rhythmicity is not present in primary OASF and RASF, which is unexpected because fibroblasts usually demonstrate perfect rhythms during several days. This might lead to uncoupling of important cellular pathways.
Aberrant CD200/CD200R1 expression and function in systemic lupus erythematosus contributes to abnormal T-cell responsiveness and dendritic cell activity
Authors: Li Yang , Zhao Li-dan , Tong Lu-sha , Qian Su-ning , Ren Yan , Zhang Lei , Ding Xin , Chen Yang , Wang Yan-xia , Zhang Wen , Zeng Xiao-feng , Zhang Feng-chun , Tang Fu-lin , Zhang Xuan , Ba De-nian , He Wei , Cao Xue-tao , Lipsky Peter E
Published: June 2012

Introduction

CD200 is a type I transmembrane glycoprotein that can regulate the activation threshold of inflammatory immune responses, polarize cytokine production, and maintain immune homeostasis. We therefore evaluated the functional status of CD200/CD200 receptor 1 (CD200R1) interactions in subjects with systemic lupus erythematosus (SLE).

Methods

Serum CD200 level was detected by ELISA. The expression of CD200/CD200R1 by CD4+ T cells and dendritic cells (DCs) was examined by flow cytometry, and then compared between SLE patients and healthy controls. Peripheral blood mononuclear cells were stained with carboxyfluorescein diacetate succinimidyl ester and annexin V/propidium iodide for evaluation of the effect of CD200 on cell proliferation and apoptosis. In addition, the effect of CD200 on DC function was determined by transwell migration assay as well as by measurement of binding and phagocytosis of apoptotic cells.

Results

In SLE patients, the number of CD200+ cells and the level of soluble CD200 were significantly higher than in healthy controls, whereas the expression of CD200R1 by CD4+ T cells and DCs was decreased. Furthermore, the increased CD200 expression by early apoptotic cells contributed to their diminished binding and phagocytosis by DCs in SLE. Importantly, the engagement of CD200 receptor on CD4+ T cells with CD200-Fc fusion protein in vitro reduced the differentiation of T-helper type 17 cells and reversed the defective induction of CD4+CD25highFoxP3+ T cells by transforming growth factor beta in SLE patients. Conversely, blockade of CD200-CD200R1 interaction with anti-CD200R1 antibody promoted CD4+ T-cell proliferation.

Conclusion

CD200 and CD200R1 expression and function are abnormal in SLE and may contribute to the immunologic abnormalities in SLE.