bluuebunny/crossref_metadata_2025 huggingface dataset:
Xenografts of highly resistant leukemia recapitulate the clonal composition of the leukemogenic compartment
Authors: Schmitz Maike , Breithaupt Petra , Scheidegger Nastassja , Cario Gunnar , Bonapace Laura , Meissner Barbara , Mirkowska Paulina , Tchinda Joelle , Niggli Felix K. , Stanulla Martin , Schrappe Martin , Schrauder Andre , Bornhauser Beat C. , Bourquin Jean-Pierre
Published: June 2011

Clonal evolution of the leukemogenic compartment may contribute to alter the therapeutic response in acute lymphoblastic leukemia (ALL). Using xenotransplantation of primary leukemia cells, we evaluated the phenotypic and genetic composition of de novo resistant very high risk precursor B-cell ALL, a subgroup defined by the persistence of minimal residual disease despite intensive chemotherapy. Analysis of copy number alterations (CNAs) showed that the xenografted leukemia, even when reconstituted from 100 cells, remained highly related to the diagnostic sample, with minor changes in CNAs, mostly deletions, emerging in most cases in the first passage into mice. At the single-cell level, the pattern of monoallelic and biallelic deletions of the CDKN2A locus revealed distinct leukemia subpopulations, which were reproducibly tracked in xenografts. In most very high risk ALL cases, the predominant diagnostic clones were reconstituted in xenografts, as shown by multiplex polymerase chain reaction analysis of immunoglobulin and T-cell receptor loci. In other cases, the pattern in CNAs and immunoglobulin and T-cell receptor rearrangement was less concordant in xenografts, suggesting the outgrowth of subclones. These results unequivocally demonstrate the existence of clonally closely related but distinct subsets of leukemia initiating cells in ALL, which has important implications for drug development and preclinical disease modeling.
Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials
Authors: Fayers Peter M. , Palumbo Antonio , Hulin Cyrille , Waage Anders , Wijermans Pierre , Beksaç Meral , Bringhen Sara , Mary Jean-Yves , Gimsing Peter , Termorshuizen Fabian , Haznedar Rauf , Caravita Tommaso , Moreau Philippe , Turesson Ingemar , Musto Pellegrino , Benboubker Lotfi , Schaafsma Martijn , Sonneveld Pieter , Facon Thierry ,   on behalf of the Nordic Myeloma Study Group, Italian Multiple Myeloma Network, Turkish Myeloma Study Group, Hemato-Oncologie voor Volwassenen Nederland, Intergroupe Francophone du Myélome, and European Myeloma Network
Published: June 2011

The role of thalidomide for previously untreated elderly patients with multiple myeloma remains unclear. Six randomized controlled trials, launched in or after 2000, compared melphalan and prednisone alone (MP) and with thalidomide (MPT). The effect on overall survival (OS) varied across trials. We carried out a meta-analysis of the 1685 individual patients in these trials. The primary endpoint was OS, and progression-free survival (PFS) and 1-year response rates were secondary endpoints. There was a highly significant benefit to OS from adding thalidomide to MP (hazard ratio = 0.83; 95% confidence interval 0.73-0.94, P = .004), representing increased median OS time of 6.6 months, from 32.7 months (MP) to 39.3 months (MPT). The thalidomide regimen was also associated with superior PFS (hazard ratio = 0.68, 95% confidence interval 0.61-0.76, P < .0001) and better 1-year response rates (partial response or better was 59% on MPT and 37% on MP). Although the trials differed in terms of patient baseline characteristics and thalidomide regimens, there was no evidence that treatment affected OS differently according to levels of the prognostic factors. We conclude that thalidomide added to MP improves OS and PFS in previously untreated elderly patients with multiple myeloma, extending the median survival time by on average 20%.
Efficient alignment of pyrosequencing reads for re-sequencing applications
Authors: Fernandes Francisco , da Fonseca Paulo GS , Russo Luis MS , Oliveira Arlindo L , Freitas Ana T
Published: June 2011

Background

Over the past few years, new massively parallel DNA sequencing technologies have emerged. These platforms generate massive amounts of data per run, greatly reducing the cost of DNA sequencing. However, these techniques also raise important computational difficulties mostly due to the huge volume of data produced, but also because of some of their specific characteristics such as read length and sequencing errors. Among the most critical problems is that of efficiently and accurately mapping reads to a reference genome in the context of re-sequencing projects.

Results

We present an efficient method for the local alignment of pyrosequencing reads produced by the GS FLX (454) system against a reference sequence. Our approach explores the characteristics of the data in these re-sequencing applications and uses state of the art indexing techniques combined with a flexible seed-based approach, leading to a fast and accurate algorithm which needs very little user parameterization. An evaluation performed using real and simulated data shows that our proposed method outperforms a number of mainstream tools on the quantity and quality of successful alignments, as well as on the execution time.

Conclusions

The proposed methodology was implemented in a software tool called TAPyR--Tool for the Alignment of Pyrosequencing Reads--which is publicly available from http://www.tapyr.net.
Global analysis of gene expression in mineralizing fish vertebra-derived cell lines: new insights into anti-mineralogenic effect of vanadate
Authors: Tiago Daniel M , Laizé Vincent , Bargelloni Luca , Ferraresso Serena , Romualdi Chiara , Cancela M Leonor
Published: June 2011

Background

Fish has been deemed suitable to study the complex mechanisms of vertebrate skeletogenesis and gilthead seabream (Sparus aurata), a marine teleost with acellular bone, has been successfully used in recent years to study the function and regulation of bone and cartilage related genes during development and in adult animals. Tools recently developed for gilthead seabream, e.g. mineralogenic cell lines and a 4 × 44K Agilent oligo-array, were used to identify molecular determinants of in vitro mineralization and genes involved in anti-mineralogenic action of vanadate.

Results

Global analysis of gene expression identified 4,223 and 4,147 genes differentially expressed (fold change - FC > 1.5) during in vitro mineralization of VSa13 (pre-chondrocyte) and VSa16 (pre-osteoblast) cells, respectively. Comparative analysis indicated that nearly 45% of these genes are common to both cell lines and gene ontology (GO) classification is also similar for both cell types. Up-regulated genes (FC > 10) were mainly associated with transport, matrix/membrane, metabolism and signaling, while down-regulated genes were mainly associated with metabolism, calcium binding, transport and signaling. Analysis of gene expression in proliferative and mineralizing cells exposed to vanadate revealed 1,779 and 1,136 differentially expressed genes, respectively. Of these genes, 67 exhibited reverse patterns of expression upon vanadate treatment during proliferation or mineralization.

Conclusions

Comparative analysis of expression data from fish and data available in the literature for mammalian cell systems (bone-derived cells undergoing differentiation) indicate that the same type of genes, and in some cases the same orthologs, are involved in mechanisms of in vitro mineralization, suggesting their conservation throughout vertebrate evolution and across cell types. Array technology also allowed identification of genes differentially expressed upon exposure of fish cell lines to vanadate and likely involved in its anti-mineralogenic activity. Many were found to be unknown or they were never associated to bone homeostasis previously, thus providing a set of potential candidates whose study will likely bring insights into the complex mechanisms of tissue mineralization and bone formation.
Proteomic analysis of the carotenogenic yeast Xanthophyllomyces dendrorhous
Authors: Martinez-Moya Pilar , Watt Steven Alexander , Niehaus Karsten , Alcaíno Jennifer , Baeza Marcelo , Cifuentes Víctor
Published: June 2011

Background

The yeast Xanthophyllomyces dendrorhous is used for the microbiological production of the antioxidant carotenoid astaxanthin. In this study, we established an optimal protocol for protein extraction and performed the first proteomic analysis of the strain ATCC 24230. Protein profiles before and during the induction of carotenogenesis were determined by two-dimensional polyacrylamide gel electrophoresis and proteins were identified by mass spectrometry.

Results

Among the approximately 600 observed protein spots, 131 non-redundant proteins were identified. Proteomic analyses allowed us to identify 50 differentially expressed proteins that fall into several classes with distinct expression patterns. These analyses demonstrated that enzymes related to acetyl-CoA synthesis were more abundant prior to carotenogenesis. Later, redox- and stress-related proteins were up-regulated during the induction of carotenogenesis. For the carotenoid biosynthetic enzymes mevalonate kinase and phytoene/squalene synthase, we observed higher abundance during induction and/or accumulation of carotenoids. In addition, classical antioxidant enzymes, such as catalase, glutathione peroxidase and the cytosolic superoxide dismutases, were not identified.

Conclusions

Our results provide an overview of potentially important carotenogenesis-related proteins, among which are proteins involved in carbohydrate and lipid biosynthetic pathways as well as several redox- and stress-related proteins. In addition, these results might indicate that X. dendrorhous accumulates astaxanthin under aerobic conditions to scavenge the reactive oxygen species (ROS) generated during metabolism.
MeRy-B: a web knowledgebase for the storage, visualization, analysis and annotation of plant NMR metabolomic profiles
Authors: Ferry-Dumazet Hélène , Gil Laurent , Deborde Catherine , Moing Annick , Bernillon Stéphane , Rolin Dominique , Nikolski Macha , de Daruvar Antoine , Jacob Daniel
Published: June 2011

Background

Improvements in the techniques for metabolomics analyses and growing interest in metabolomic approaches are resulting in the generation of increasing numbers of metabolomic profiles. Platforms are required for profile management, as a function of experimental design, and for metabolite identification, to facilitate the mining of the corresponding data. Various databases have been created, including organism-specific knowledgebases and analytical technique-specific spectral databases. However, there is currently no platform meeting the requirements for both profile management and metabolite identification for nuclear magnetic resonance (NMR) experiments.

Description

MeRy-B, the first platform for plant1H-NMR metabolomic profiles, is designed (i) to provide a knowledgebase of curated plant profiles and metabolites obtained by NMR, together with the corresponding experimental and analytical metadata, (ii) for queries and visualization of the data, (iii) to discriminate between profiles with spectrum visualization tools and statistical analysis, (iv) to facilitate compound identification. It contains lists of plant metabolites and unknown compounds, with information about experimental conditions, the factors studied and metabolite concentrations for several plant species, compiled from more than one thousand annotated NMR profiles for various organs or tissues.

Conclusion

MeRy-B manages all the data generated by NMR-based plant metabolomics experiments, from description of the biological source to identification of the metabolites and determinations of their concentrations. It is the first database allowing the display and overlay of NMR metabolomic profiles selected through queries on data or metadata. MeRy-B is available fromhttp://www.cbib.u-bordeaux2.fr/MERYB/index.php.
Endoscopic papillary large balloon dilation alone without sphincterotomy for the treatment of large common bile duct stones
Authors: Chan Hoi-Hung , Lai Kwok-Hung , Lin Chiun-Ku , Tsai Wei-Lun , Wang E-Ming , Hsu Ping-I , Chen Wen-Chi , Yu Hsien-Chung , Wang Huay-Min , Tsay Feng-Woei , Tsai Cheng-chung , Chen I-Shu , Chen Yu-chia , Liang Huei-Lung , Pan Huay-Ben
Published: June 2011

Background

Lethal pancreatitis has been reported after treatment for common bile duct stones using small endoscopic papillary balloon dilation.

Methods

We retrospectively evaluated the safety and efficacy of using large balloon dilation alone without the use of sphincterotomy for the treatment of large common bile duct stones in Kaohsiung Veterans General Hospital. Success rate of stone clearance, procedure-related adverse events and incidents, frequency of mechanical lithotripsy use, and recurrent stones were recorded.

Results

A total of 247 patients were reviewed in the current study. The mean age of the patients was 71.2 years. Most of them had comorbidities. Mean stone size was 16.4 mm. Among the patients, 132 (53.4%) had an intact gallbladder and 121 (49%) had a juxtapapillary diverticulum. The mean size of dilating balloon used was 13.2 mm. The mean duration of the dilating procedure was 4.7 min. There were 39 (15.8%) patients required the help of mechanical lithotripsy while retrieving the stones. The final success rate of complete retrieval of stones was 92.7%. The rate of pancreatic duct enhancement was 26.7% (66/247). There were 3 (1.2%) adverse events and 6 (2.4%) intra-procedure bleeding incidents. All patients recovered completely after conservative and endoscopic treatment respectively, and no procedure-related mortality was noted. 172 patients had a follow-up duration of more than 6 months and among these, 25 patients had recurrent common bile duct stones. It was significantly correlated to the common bile duct size (p = 0.036)

Conclusions

Endoscopic papillary large balloon dilation alone is simple, safe, and effective in dealing with large common bile duct stones in relatively aged and debilitated patients.
COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status
Authors: Asting Annika Gustafsson , Carén Helena , Andersson Marianne , Lönnroth Christina , Lagerstedt Kristina , Lundholm Kent
Published: June 2011

Background

Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue.

Method

Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated.

Results

Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4) showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3) were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue.

Conclusions

Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue.
Evaluation of primary HPV-DNA testing in relation to visual inspection methods for cervical cancer screening in rural China: an epidemiologic and cost-effectiveness modelling study
Authors: Shi Ju-Fang , Canfell Karen , Lew Jie-Bin , Zhao Fang-Hui , Legood Rosa , Ning Yan , Simonella Leonardo , Ma Li , Kang Yoon-Jung , Zhang Yong-Zhen , Smith Megan A , Chen Jun-Feng , Feng Xiang-Xian , Qiao You-Lin
Published: June 2011

Background

A new lower-cost rapid-throughput human papillomavirus (HPV) test (careHPV, Qiagen, Gaithersburg, USA) has been shown to have high sensitivity for the detection of high grade cervical intraepithelial neoplasia.

Methods

We assessed the outcomes and cost-effectiveness ofcareHPV screening in rural China, compared to visual inspection with acetic acid, when used alone (VIA) or in combination with Lugol's iodine (VIA/VILI). Using data on sexual behaviour, test accuracy, diagnostic practices and costs from studies performed in rural China, we estimated the cost-effectiveness ratio (CER) and associated lifetime outcomes for once-lifetime and twice-lifetime screening strategies, and for routine screening at 5-yearly, 10-yearly and IARC-recommended intervals. The optimal age range for once-lifetime screening was also assessed.

Results

For all strategies, the relative ordering of test technologies in reducing cervical cancer incidence and mortality was VIA (least effective); VIA/VILI;careHPV@1.0 pg/ml andcareHPV@0.5 pg/ml (most effective). For once-lifetime strategies, maximum effectiveness was achieved if screening occurred between 35-50 years. Assuming a participation rate of ~70%, once-lifetime screening at age 35 years would reduce cancer mortality by 8% (for VIA) to 12% (forcareHPV@0.5) over the long term, with a CER of US$557 (for VIA) to $959 (forcareHPV@1.0) per life year saved (LYS) compared to no intervention; referenced to a 2008 GDP per capita in Shanxi Province of $2,975. Correspondingly, regular screening with an age-standardised participation rate of 62% (which has been shown to be achievable in this setting) would reduce cervical cancer mortality by 19-28% (for 10-yearly screening) to 43-54% (using IARC-recommended intervals), with corresponding CERs ranging from $665 (for 10-yearly VIA) to $2,269 (for IARC-recommended intervals usingcareHPV@1.0) per LYS.

Conclusions

This modelled analysis suggests that primarycareHPV screening compares favourably to visual inspection screening methodologies in rural China, particularly if used as part of a regular screening program.
Renal cell carcinoma primary cultures maintain genomic and phenotypic profile of parental tumor tissues
Authors: Cifola Ingrid , Bianchi Cristina , Mangano Eleonora , Bombelli Silvia , Frascati Fabio , Fasoli Ester , Ferrero Stefano , Di Stefano Vitalba , Zipeto Maria A , Magni Fulvio , Signorini Stefano , Battaglia Cristina , Perego Roberto A
Published: June 2011

Background

Clear cell renal cell carcinoma (ccRCC) is characterized by recurrent copy number alterations (CNAs) and loss of heterozygosity (LOH), which may have potential diagnostic and prognostic applications. Here, we explored whether ccRCC primary cultures, established from surgical tumor specimens, maintain the DNA profile of parental tumor tissues allowing a more confident CNAs and LOH discrimination with respect to the original tissues.

Methods

We established a collection of 9 phenotypically well-characterized ccRCC primary cell cultures. Using the Affymetrix SNP array technology, we performed the genome-wide copy number (CN) profiling of both cultures and corresponding tumor tissues. Global concordance for each culture/tissue pair was assayed evaluating the correlations between whole-genome CN profiles and SNP allelic calls. CN analysis was performed using the two CNAG v3.0 and Partek software, and comparing results returned by two different algorithms (Hidden Markov Model and Genomic Segmentation).

Results

A very good overlap between the CNAs of each culture and corresponding tissue was observed. The finding, reinforced by high whole-genome CN correlations and SNP call concordances, provided evidence that each culture was derived from its corresponding tissue and maintained the genomic alterations of parental tumor. In addition, primary culture DNA profile remained stable for at least 3 weeks, till to third passage. These cultures showed a greater cell homogeneity and enrichment in tumor component than original tissues, thus enabling a better discrimination of CNAs and LOH. Especially for hemizygous deletions, primary cultures presented more evident CN losses, typically accompanied by LOH; differently, in original tissues the intensity of these deletions was weaken by normal cell contamination and LOH calls were missed.

Conclusions

ccRCC primary cultures are a reliable in vitro model, well-reproducing original tumor genetics and phenotype, potentially useful for future functional approaches aimed to study genes or pathways involved in ccRCC etiopathogenesis and to identify novel clinical markers or therapeutic targets. Moreover, SNP array technology proved to be a powerful tool to better define the cell composition and homogeneity of RCC primary cultures.
FAP-overexpressing fibroblasts produce an extracellular matrix that enhances invasive velocity and directionality of pancreatic cancer cells
Authors: Lee Hyung-Ok , Mullins Stefanie R , Franco-Barraza Janusz , Valianou Matthildi , Cukierman Edna , Cheng Jonathan D
Published: June 2011

Background

Alterations towards a permissive stromal microenvironment provide important cues for tumor growth, invasion, and metastasis. In this study, Fibroblast activation protein (FAP), a serine protease selectively produced by tumor-associated fibroblasts in over 90% of epithelial tumors, was used as a platform for studying tumor-stromal interactions.

We tested the hypothesis that FAP enzymatic activity locally modifies stromal ECM (extracellular matrix) components thus facilitating the formation of a permissive microenvironment promoting tumor invasion in human pancreatic cancer.

Methods

We generated a tetracycline-inducible FAP overexpressing fibroblastic cell line to synthesize an in vivo-like 3-dimensional (3D) matrix system which was utilized as a stromal landscape for studying matrix-induced cancer cell behaviors. A FAP-dependent topographical and compositional alteration of the ECM was characterized by measuring the relative orientation angles of fibronectin fibers and by Western blot analyses. The role of FAP in the matrix-induced permissive tumor behavior was assessed in Panc-1 cells in assorted matrices by time-lapse acquisition assays. Also, FAP+ matrix-induced regulatory molecules in cancer cells were determined by Western blot analyses.

Results

We observed that FAP remodels the ECM through modulating protein levels, as well as through increasing levels of fibronectin and collagen fiber organization. FAP-dependent architectural/compositional alterations of the ECM promote tumor invasion along characteristic parallel fiber orientations, as demonstrated by enhanced directionality and velocity of pancreatic cancer cells on FAP+ matrices. This phenotype can be reversed by inhibition of FAP enzymatic activity during matrix production resulting in the disorganization of the ECM and impeded tumor invasion. We also report that the FAP+ matrix-induced tumor invasion phenotype is β1-integrin/FAK mediated.

Conclusion

Cancer cell invasiveness can be affected by alterations in the tumor microenvironment. Disruption of FAP activity and β1-integrins may abrogate the invasive capabilities of pancreatic and other tumors by disrupting the FAP-directed organization of stromal ECM and blocking β1-integrin dependent cell-matrix interactions. This provides a novel preclinical rationale for therapeutics aimed at interfering with the architectural organization of tumor-associated ECM. Better understanding of the stromal influences that fuel progressive tumorigenic behaviors may allow the effective future use of targeted therapeutics aimed at disrupting specific tumor-stromal interactions.
Intervention for depression among palliative care patients and their families: A study protocol for evaluation of a training program for professional care staff
Authors: Hallford David J , McCabe Marita P , Mellor David , Davison Tanya E , Goldhammer Denisa L , George Kuruvilla , Storer Shane
Published: June 2011

Background

Clinical depression is highly prevalent yet under-detected and under-treated in palliative care settings and is associated with a number of adverse medical and psychological outcomes for patients and their family members. This article presents a study protocol to evaluate a training intervention for non-physician palliative care staff to improve the recognition of depression and provide support for depressed patients and their family members. Details of the hypotheses and expected outcomes, study design, training program development and evaluation measures are described.

Methods and Design

A randomised controlled trial will be implemented across two palliative care services to evaluate the "Training program for professional carers to recognise and manage depression in palliative care settings". Pre-, post- and three-month follow-up data will be collected to assess: the impact of the training on the knowledge, attitudes, self-efficacy and perceived barriers of palliative care staff when working with depression; referral rates for depression; and changes to staff practices. Quantitative and qualitative methods, in the form of self-report questionnaires and interviews with staff and family members, will be used to evaluate the effectiveness of the intervention.

Discussion

This study will determine the effectiveness of an intervention that aims to respond to the urgent need for innovative programs to target depression in the palliative care setting. The expected outcome of this study is the validation of an evidence-based training program to improve staff recognition and appropriate referrals for depression, as well as improve psychosocial support for depressed patients and their family members.

Trial Registration

Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000183088
Is gynaecological surgical training a cause for concern? A questionnaire survey of trainees and trainers
Authors: Moss Esther L , Bredaki Foteini E , Jones Peter W , Hollingworth James , Luesley David M , Chan Kiong K
Published: June 2011

Astract

Background

Concerns have been raised as to whether the current postgraduate training programme for gynaecological surgery is being detrimentally affected by changes in working practices, in particular the European Working Time Directive (EWTD). The purpose of this study was to investigate the surgical activity of obstetrics and gynaecology trainees and to explore trainees' and trainers' opinions on the current barriers and potential solutions to surgical training.

Methods

Two questionnaire surveys were conducted, one to obstetrics and gynaecology trainees working within the West Midlands Deanery and a second to consultant gynaecologists in the West Midlands region.

Results

One hundred and four trainees (64.3%) and 66 consultant gynaecologists (55.0%) responded. Sixty-six trainees (66.7%) reported attending up to one operating list per week. However, 28.1% reported attending up to one list every two weeks or less and 5 trainees stated that they had not attended a list at all over the preceding 8 weeks. Trainees working in a unit with less than 3999 deliveries attended significantly more theatre sessions compared to trainees in units with over 4000 deliveries (p = 0.007), as did senior trainees (p = 0.032) and trainees attached to consultants performing major gynaecological surgery (p = 0.022). In the previous 8 weeks, only 6 trainees reported performing a total abdominal hysterectomy independently, all were senior trainees (ST6 and above). In the trainers' survey, only two respondents (3.0%) agreed that the current program produces doctors competent in general gynaecological surgery by the end of training, compared to 48 (73.8%) respondents who disagreed.

Conclusions

Trainees' concerns over a lack of surgical training appear to be justified. The main barriers to training are perceived to be a lack of team structure and a lack of theatre time.
Long-term oral nitrate therapy is associated with adverse outcome in diabetic patients following elective percutaneous coronary intervention
Authors: Hang Yiu Kai , Pong Vincent , Wah Siu Chung , Pak Lau Chu , Fat Tse Hung
Published: June 2011

Background

To assess the impact of long-term oral nitrate therapy on clinical outcome following percutaneous coronary intervention (PCI) in patients with type II diabetes.

Methods

The incidence of major adverse cardiovascular events (MACEs) following elective PCI for stable coronary artery disease was evaluated in 108 patients with type II diabetes (age 64.6 ± 10.5 years, 67.7% men). Major adverse cardiovascular events were defined as the need for revascularization, non-fatal myocardial infarction or cardiovascular death. Multivariate Cox regression analysis was used to evaluate the predictive value of MACEs by clinical characteristics and the prescription of long-term nitrate therapy.

Results

Isosorbide mononitrate (ISMN) was prescribed to 46 patients with an average dose of 44.3 ± 15.2 mg/day. After a mean follow up of 25.3 ± 25 months, 16 patients developed MACEs. Patients who received ISMN were more likely to suffer from MACEs (26.1% vs. 6.5%, P = 0.01), mainly driven by a higher rate of acute coronary syndrome (13.0 vs 0%, P = 0.01). Average daily dose of nitrate and other cardiovascular medication was not associated with MACEs. Multivariate Cox regression analysis revealed that prescription of only ISMN (Hazard Ratio 3.09, 95% CI 1.10-10.21, P = 0.04) was an independent predictor for the development of MACEs.

Conclusion

Long-term oral nitrate therapy was associated with MACEs following elective coronary artery revascularization by PCI in patients with type II diabetes.
Effects of preoperative feeding with a whey protein plus carbohydrate drink on the acute phase response and insulin resistance. A randomized trial
Authors: Perrone Francine , da-Silva-Filho Antônio C , Adôrno Isa F , Anabuki Nadia T , Leal Fernando S , Colombo Tariane , da Silva Benedito D , Dock-Nascimento Diana B , Damião Aderson , de Aguilar-Nascimento José E
Published: June 2011

Background

Prolonged preoperative fasting increases insulin resistance and current evidence recommends carbohydrate (CHO) drinks 2 hours before surgery. Our hypothesis is that the addition of whey protein to a CHO-based drink not only reduces the inflammatory response but also diminish insulin resistance.

Methods

Seventeen patients scheduled to cholecystectomy or inguinal herniorraphy were randomized and given 474 ml and 237 ml of water (CO group) or a drink containing CHO and milk whey protein (CHO-P group) respectively, 6 and 3 hours before operation. Blood samples were collected before surgery and 24 hours afterwards for biochemical assays. The endpoints of the study were the insulin resistance (IR), the prognostic inflammatory and nutritional index (PINI) and the C-reactive protein (CRP)/albumin ratio. A 5% level for significance was established.

Results

There were no anesthetic or postoperative complications. The post-operative IR was lower in the CHO-P group when compared with the CO group (2.75 ± 0.72 vs 5.74 ± 1.16; p = 0.03). There was no difference between the two groups in relation to the PINI. The CHO-P group showed a decrease in the both CRP elevation and CRP/albumin ratio (p < 0.05). The proportion of patients who showed CRP/albumin ratio considered normal was significantly greater (p < 0.05) in the CHO-P group (87.5%) than in the CO group (33.3%).

Conclusions

Shortening the pre-operative fasting using CHO and whey protein is safe and reduces insulin resistance and postoperative acute phase response in elective moderate operations.

Trial registration

ClinicalTrail.gov NCT01354249
Rapeseed oil fortified with micronutrients reduces atherosclerosis risk factors in rats fed a high-fat diet
Authors: Xu Jiqu , Zhou Xiaoqi , Deng Qianchun , Huang Qingde , Yang Jin'e , Huang Fenghong
Published: June 2011

Background

Micronutrients polyphenols, tocopherols and phytosterols in rapeseed exert potential benefit to cardiovascular system, but most of these micronutrients are removed by the refining process. The aim of this study was to determine the effect of rapeseed oil fortified with these micronutrients on the atherosclerosis risk factors in rats fed a high-fat diet.

Methods

The rodent diet contained 20% fat whose source was refined rapeseed oil (RRO) or fortified refined rapeseed oil with low, middle and high quantities of these micronutrients (L-, M- and H-FRRO). Forty male SD rats were divided into four groups. One group received RRO diet and other groups received L-, M- and H-FRRO diet for 10 weeks.

Results

Micronutrients supplementation significantly increased plasma antioxidant defense capacities, as evaluated by the significant elevation in the activities of GPx, CAT and SOD as well as the level of GSH, and the significant decline in lipid peroxidation. These micronutrients also reduced the plasma contents of TG, TC and LDL-C and increased the ratio of HDL-C/LDL-C. In addition, in parallel with the enhancement of these micronutrients, plasma levels of IL-6 and CRP declined remarkably.

Conclusion

Rapeseed oil fortified with micronutrients polyphenols, tocopherols and phytosterols may contribute to prevent atherogenesis by ameliorating plasma oxidative stress, lipid profile and inflammation.
Oral Health-Related Quality of Life among a large national cohort of 87,134 Thai adults
Authors: Yiengprugsawan Vasoontara , Somkotra Tewarit , Seubsman Sam-ang , Sleigh Adrian C ,   The Thai Cohort Study Team
Published: June 2011

Background

Oral health has been of interest in many low and middle income countries due to its impact on general health and quality of life. But there are very few population-based reports of adult Oral Health Related Quality of Life (OHRQoL) in developing countries. To address this knowledge gap for Thailand, we report oral health findings from a national cohort of 87,134 Thai adults aged between 15 and 87 years and residing all over the country.

Methods

In 2005, a comprehensive health questionnaire was returned by distance learning cohort members recruited through Sukhothai Thammathirat Open University. OHRQoL dimensions included were discomfort speaking, swallowing, chewing, social interaction and pain. We calculated multivariate (adjusted) associations between OHRQoL outcomes, and sociodemographic, health behaviour and dental status.

Results

Overall, discomfort chewing (15.8%), social interaction (12.5%), and pain (10.6%) were the most commonly reported problems. Females were worse off for chewing, social interaction and pain. Smokers had worse OHRQoL in all dimensions with Odds Ratios (OR) ranging from 1.32 to 1.51. Having less than 20 teeth was strongly associated with difficulty speaking (OR = 6.43), difficulty swallowing (OR = 6.27), and difficulty chewing (OR = 3.26).

Conclusions

Self-reported adverse oral health correlates with individual function and quality of life. Outcomes are generally worse among females, the poor, smokers, drinkers and those who have less than 20 teeth. Further longitudinal study of the cohort analysed here will permit assessment of causal determinants of poor oral health and the efficacy of preventive programs in Thailand.
CdTe quantum dots with daunorubicin induce apoptosis of multidrug-resistant human hepatoma HepG2/ADM cells: in vitro and in vivo evaluation
Authors: Zhang Gen , Shi Lixin , Selke Matthias , Wang Xuemei
Published: June 2011

Cadmium telluride quantum dots (Cdte QDs) have received significant attention in biomedical research because of their potential in disease diagnosis and drug delivery. In this study, we have investigated the interaction mechanism and synergistic effect of 3-mercaptopropionic acid-capped Cdte QDs with the anti-cancer drug daunorubicin (DNR) on the induction of apoptosis using drug-resistant human hepatoma HepG2/ADM cells. Electrochemical assay revealed that Cdte QDs readily facilitated the uptake of the DNR into HepG2/ADM cells. Apoptotic staining, DNA fragmentation, and flow cytometry analysis further demonstrated that compared with Cdte QDs or DNR treatment alone, the apoptosis rate increased after the treatment of Cdte QDs together with DNR in HepG2/ADM cells. We observed that Cdte QDs treatment could reduce the effect of P-glycoprotein while the treatment of Cdte QDs together with DNR can clearly activate apoptosis-related caspases protein expression in HepG2/ADM cells. Moreover, ourin vivostudy indicated that the treatment of Cdte QDs together with DNR effectively inhibited the human hepatoma HepG2/ADM nude mice tumor growth. The increased cell apoptosis rate was closely correlated with the enhanced inhibition of tumor growth in the studied animals. Thus, Cdte QDs combined with DNR may serve as a possible alternative for targeted therapeutic approaches for some cancer treatments.
Positive solutions for a coupled system of nonlinear differential equations of mixed fractional orders
Authors: Zhao Yige , Sun Shurong , Han Zhenlai , Feng Wenquan
Published: June 2011

In this article, we study the existence of positive solutions for a coupled system of nonlinear differential equations of mixed fractional orders

"Equation missing"

where 2 < α ≤ 3, 3 < β ≤ 4, "Equation missing", "Equation missing" are the standard Riemann-Liouville fractional derivative, and f, g : [0, 1] × [0, +∞) → [0, +∞) are given continuous functions, f(t, 0) ≡ 0, g(t, 0) ≡ 0. Our analysis relies on fixed point theorems on cones. Some sufficient conditions for the existence of at least one or two positive solutions for the boundary value problem are established. As an application, examples are presented to illustrate the main results.
Dopamine D1-D2 receptor heteromer signaling pathway in the brain: emerging physiological relevance
Authors: Hasbi Ahmed , O'Dowd Brian F , George Susan R
Published: June 2011

Dopamine is an important catecholamine neurotransmitter modulating many physiological functions, and is linked to psychopathology of many diseases such as schizophrenia and drug addiction. Dopamine D1 and D2 receptors are the most abundant dopaminergic receptors in the striatum, and although a clear segregation between the pathways expressing these two receptors has been reported in certain subregions, the presence of D1-D2 receptor heteromers within a unique subset of neurons, forming a novel signaling transducing functional entity has been shown. Recently, significant progress has been made in elucidating the signaling pathways activated by the D1-D2 receptor heteromer and their potential physiological relevance.
Effect of a structurally modified human granulocyte colony stimulating factor, G-CSFa, on leukopenia in mice and monkeys
Authors: Jiang Yongping , Jiang Wenhong , Qiu Yuchang , Dai Wei
Published: June 2011

Background

Granulocyte colony stimulating factor (G-CSF) regulates survival, proliferation, and differentiation of neutrophilic granulocyte precursors, Recombinant G-CSF has been used for the treatment of congenital and therapy-induced neutropenia and stem cell mobilization. Due to its intrinsic instability, recombinant G-CSF needs to be excessively and/or frequently administered to patients in order to maintain a plasma concentration high enough to achieve therapeutic effects. Therefore, there is a need for the development of G-CSF derivatives that are more stable and active in vivo.

Methods

Using site-direct mutagenesis and recombinant DNA technology, a structurally modified derivative of human G-CSF termed G-CSFa was obtained. G-CSFa contains alanine 17 (instead of cysteine 17 as in wild-type G-CSF) as well as four additional amino acids including methionine, arginine, glycine, and serine at the amino-terminus. Purified recombinant G-CSFa was tested for its in vitro activity using cell-based assays and in vivo activity using both murine and primate animal models.

Results

In vitro studies demonstrated that G-CSFa, expressed in and purified from E. coli, induced a much higher proliferation rate than that of wild-type G-CSF at the same concentrations. In vivo studies showed that G-CSFa significantly increased the number of peripheral blood leukocytes in cesium-137 irradiated mice or monkeys with neutropenia after administration of clyclophosphamide. In addition, G-CSFa increased neutrophil counts to a higher level in monkeys with a concomitant slower declining rate than that of G-CSF, indicating a longer half-life of G-CSFa. Bone marrow smear analysis also confirmed that G-CSFa was more potent than G-CSF in the induction of granulopoiesis in bone marrows of myelo-suppressed monkeys.

Conclusion

G-CSFa, a structurally modified form of G-CSF, is more potent in stimulating proliferation and differentiation of myeloid cells of the granulocytic lineage than the wild-type counterpart both in vitro and in vivo. G-CSFa can be explored for the development of a new generation of recombinant therapeutic drug for leukopenia.
Base-By-Base version 2: single nucleotide-level analysis of whole viral genome alignments
Authors: Hillary William , Lin Song-Han , Upton Chris
Published: June 2011

Background

Base-By-Base is a Java-based multiple sequence alignment editor. It is capable of working with protein and DNA molecules, but many of its unique features relate to the manipulation of the genomes of large DNA viruses such as poxviruses, herpesviruses, baculoviruses and asfarviruses (1-400 kb). The tool was built to serve as a platform for comparative genomics at the level of individual nucleotides.

Results

In version 2, BBB-v2, of Base-By-Base we have added a series of new features aimed at providing the bench virologist with a better platform to view, annotate and analyze these complex genomes. Although a poxvirus genome, for example, may be less than 200 kb, it probably encodes close to 200 proteins using multiple classes of promoters with frequent overlapping of promoters and coding sequences and even some overlapping of genes. The new features allow users to 1) add primer annotations or other data sets in batch mode, 2) export differences between sequences to other genome browsers, 3) compare multiple genomes at a single nucleotide level of detail, 4) create new alignments from subsets/subsequences of a very large master alignment and 5) allow display of summaries of deep RNA sequencing data sets on a genome sequence.

Conclusion

BBB-v2 significantly improves the ability of virologists to work with genome sequences and provides a platform with which they can use a multiple sequence alignment as the basis for their own editable documents. Also, a .bbb document, with a variety of annotations in addition to the basic coding regions, can be shared among collaborators or made available to an entire research community. The program is available via Virology.ca using Java Web Start and is platform independent; the Java 1.5 virtual machine is required.
Introduction to this special section: Africa
Authors: Olotu Samuel , Detomo Rocco , Jackson Alan
Published: June 2011

Africa has long been a place for successful mineral and oil and gas exploration; however, the diversity of geology, technical innovation, and opportunity make it a unique place. A single special section cannot hope to capture the breadth of the geophysical activity going on today somewhere on the continent. But we hope that with this issue we at least make a dent in the subject by offering a good variety of papers from both hard rock and hydrocarbon exploration.
Neutron, X-ray and dual gamma-ray radiography and tomography of geomaterial—A South African perspective
Authors: De Beer Frikkie , Ameglio Laurent
Published: June 2011

Characterization and quantification of physical properties and contents of geomaterials and rocks is the subject of various conventional and nonconventional analyses.
Biology and Clinical Relevance of the Micropthalmia Family of Transcription Factors in Human Cancer
Authors: Haq Rizwan , Fisher David E.
Published: June 2011

Members of the micropthalmia (MiT) family of transcription factors (MITF, TFE3, TFEB, and TFEC) are physiologic regulators of cell growth, differentiation, and survival in several tissue types. Because their dysregulation can lead to melanoma, renal cell carcinoma, and some sarcomas, understanding why these genes are co-opted in carcinogenesis may be of general utility. Here we describe the structure of the MiT family of proteins, the ways in which they are aberrantly activated, and the molecular mechanisms by which they promote oncogenesis. We discuss how meaningful understanding of these mechanisms can be used to elucidate the oncogenic process. Because the expression of these proteins is essential for initiating and maintaining the oncogenic state in some cancer types, we propose ways that they can be exploited to prevent, diagnose, and rationally treat these malignancies.
Interpretation in Consultations With Immigrant Patients With Cancer: How Accurate Is It?
Authors: Butow Phyllis N. , Goldstein David , Bell Melaine L. , Sze Ming , Aldridge Lynley J. , Abdo Sarah , Tanious Michelle , Dong Skye , Iedema Rick , Vardy Janette , Ashgari Ray , Hui Rina , Eisenbruch Maurice
Published: June 2011

Purpose

Immigrants with cancer often have professional and/or family interpreters to overcome challenges communicating with their health team. This study explored the rate and consequences of nonequivalent interpretation in medical oncology consultations.

Patients and Methods

Consecutive immigrant patients with newly diagnosed with incurable cancer, who spoke Arabic, Cantonese, Mandarin, or Greek, were recruited from the practices of 10 medical oncologists in nine hospitals. Their first two consultations were audio taped, transcribed, translated into English and coded.

Results

Thirty-two of 78 participants had an interpreter at 49 consultations; 43% of interpreters were family, 35% professional, 18% both a professional and family, and 4% a health professional. Sixty-five percent of professional interpretations were equivalent to the original speech versus 50% for family interpreters (P= .02). Seventy percent of nonequivalent interpretations were inconsequential or positive; however, 10% could result in misunderstanding, in 5% the tone was more authoritarian than originally intended, and in 3% more certainty was conveyed. There were no significant differences in interpreter type for equivalency of interpretations.

Conclusion

Nonequivalent interpretation is common, and not always innocuous. Our study suggests that there may remain a role for family or telephone versus face-to-face professional interpreters. Practice implications: careful communication between oncologists and interpreters is required to ensure optimal communication with the patient.
Proportional–derivative impedance control of robot manipulators for interaction tasks
Authors: Mendoza-Gutiérrez M , Reyes F , Bonilla-Gutiérrez I , González-Galván E
Published: June 2011

This paper addresses the problem of impedance control of robot manipulators. An impedance controller with dynamic compensation, applied to the interaction control of robot manipulators, is presented. Previous results on motion control in task-space are extended to generate the proposed impedance controller. The approach was designed in such a way that it solves two challenges: the regulation of the interaction and a suitable path tracking. The asymptotic stability of the closed-loop system, composed by full non-linear robot dynamics and the impedance controller, is demonstrated in agreement with Lyapunov’s direct method. In addition to the theoretical background, the performance of the proposed controller is verified through simulation and experimental results obtained from the implementation of an interaction task involving a two degree-of-freedom, direct-drive robot.