bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scaffold-Guided Subchondral Bone Repair
Authors: Hoemann Caroline D. , Chen Gaoping , Marchand Catherine , Tran-Khanh Nicolas , Thibault Marc , Chevrier Anik , Sun Jun , Shive Matthew S. , Fernandes Maria J. G. , Poubelle Patrice E. , Centola Michael , El-Gabalawy Hani 
Published: June 2010

Background: Microfracture and drilling elicit a cartilage repair whose quality depends on subchondral bone repair. Alternatively activated (AA) macrophages express arginase-1, release angiogenic factors, and could be potential mediators of trabecular bone repair. Hypothesis: Chitosan–glycerol phosphate (GP)/blood implants elicit arginase-1+ macrophages in vivo through neutrophil-dependent mechanisms and improve trabecular bone repair of drilled defects compared with drilling alone. Study Design: Controlled laboratory study. Methods: Bilateral trochlear cartilage defects were created in 15 rabbits, microdrilled, and treated or not with chitosan-GP/blood implant to analyze AA macrophages, CD-31+ blood vessels, bone, and cartilage repair after 1, 2, or 8 weeks. Neutrophil and macrophage chemotaxis to rabbit subcutaneous implants of autologous blood and chitosan-GP (±blood) was quantified at 1 or 7 days. In vitro, sera from human chitosan-GP/blood and whole blood clots cultured at 37°C were analyzed by proteomics and neutrophil chemotaxis assays. Results: Chitosan-GP/blood clots and whole blood clots released a similar profile of chemotactic factors (PDGF-BB, IL-8/CXCL8, MCP-1/CCL2, and no IL-1β or IL-6), although chitosan clot sera attracted more neutrophils in vitro. Subcutaneous chitosan-GP (±blood) implants attracted more neutrophils ( P < .001) and AA macrophages than whole blood clots in vivo. In repairing subchondral drill holes, chitosan-GP/blood implant attracted more AA macrophages at 1 and 2 weeks and more blood vessels at 2 weeks compared with drilled controls. Treatment elicited a more complete woven bone repair at 8 weeks than controls ( P = .0011) with a more uniform, integrated collagen type II+ cartilage repair tissue. Conclusion and Clinical Relevance: AA macrophages may play a role in the regeneration of subchondral bone, and chitosan-GP can attract and transiently accumulate these cells in the repair tissue. The resulting improved subchondral repair could be advantageous toward enhancing integration of a restored chondral surface to the subchondral bone.
A qualitative exploration of a health trainer programme in two UK primary care trusts
Authors: Ball Linda , Nasr Nasrin 
Published: June 2010

Aims: World Health Organization data illustrate a worldwide re-emergence of interest in the scope of lay health workers for extending services to ‘hard-to-reach’ community groups. In the UK, the health trainer model of service delivery represents one such innovative way of working, first described in the White Paper Choosing Health: Making Healthier Choices Easier and more recently in the Kings Fund report. The scheme was introduced into selected primary care settings in England from 2005 and rolled out nationally from 2007. The aim of this study was to examine the perceived value of the health trainer scheme. Methods: This paper describes qualitative data from two studies undertaken in 2007—2009, comprising in-depth consultations with key primary care stakeholders, health trainers and their clients in two primary care trusts in northern and central England. Data was collected via 12 semi-structured interviews with key stakeholders and service users and from 8 focus groups with a total of 33 trainee and qualified health trainers. Results: The UK health trainer approach was regarded as effective in contributing to the support of a broad spectrum of health and welfare issues across widely diverse communities in the two primary care trusts evaluated. Study data also indicated a wide-ranging impact of the health trainer service, extending not only to the lay health workers themselves, but also to their families, friends and colleagues. Conclusions: The health trainer service appears to be not only ‘fit for purpose’, but also to bring with it certain ‘added value’, which was not predicted by the two primary care service providers at the outset. A critical factor in this success appears to be the unique combination of time, the ‘person next door’ and a ‘one-to-one’ approach, which facilitated an innovative and highly productive connection between the health trainer and client. However, participants in this evaluation perceived that the current format and constituents of service performance data were significantly failing to credit the health trainer scheme with the full extent of this impact.
Radioimmunodetection of amyloid deposits in patients with AL amyloidosis
Authors: Wall Jonathan S. , Kennel Stephen J. , Stuckey Alan C. , Long Misty J. , Townsend David W. , Smith Gary T. , Wells Karen J. , Fu Yitong , Stabin Michael G. , Weiss Deborah T. , Solomon Alan 
Published: June 2010

Abstract
Care of patients with AL amyloidosis currently is limited by the lack of objective means to document disease extent, as well as therapeutic options that expedite removal of pathologic deposits. To address these issues, we have initiated a Phase I Exploratory IND study to determine the biodistribution of the fibril-reactive, amyloidolytic murine IgG1 mAb 11-1F4 labeled with I-124. Patients were infused with less than 1 mg (∼ 74 MBq) of GMP-grade antibody and imaged by PET/CT scan 48 and 120 hours later. Among 9 of 18 subjects, there was striking uptake of the reagent in liver, lymph nodes, bone marrow, intestine, or, unexpectedly, spleen (but not kidneys or heart). Generally, positive or negative results correlated with those obtained immunohistochemically using diagnostic tissue biopsy specimens. Based on these findings, we posit that 124I-mAb m11-1F4 can be used to identify AL candidates for passive immunotherapy using the chimeric form of the antibody. This trial was registered at www.clinicaltrials.gov as NCT00807872.
Heme and non-heme iron transporters in non-polarized and polarized cells
Authors: Yanatori Izumi , Tabuchi Mitsuaki , Kawai Yasuhiro , Yasui Yumiko , Akagi Reiko , Kishi Fumio 
Published: June 2010

Abstract

Background
Heme and non-heme iron from diet, and recycled iron from hemoglobin are important products of the synthesis of iron-containing molecules. In excess, iron is potentially toxic because it can produce reactive oxygen species through the Fenton reaction. Humans can absorb, transport, store, and recycle iron without an excretory system to remove excess iron. Two candidate heme transporters and two iron transporters have been reported thus far. Heme incorporated into cells is degraded by heme oxygenases (HOs), and the iron product is reutilized by the body. To specify the processes of heme uptake and degradation, and the reutilization of iron, we determined the subcellular localizations of these transporters and HOs.

Results
In this study, we analyzed the subcellular localizations of 2 isoenzymes of HOs, 4 isoforms of divalent metal transporter 1 (DMT1), and 2 candidate heme transporters--heme carrier protein 1 (HCP1) and heme responsive gene-1 (HRG-1)--in non-polarized and polarized cells. In non-polarized cells, HCP1, HRG-1, and DMT1A-I are located in the plasma membrane. In polarized cells, they show distinct localizations: HCP1 and DMT1A-I are located in the apical membrane, whereas HRG-1 is located in the basolateral membrane and lysosome. 16Leu at DMT1A-I N-terminal cytosolic domain was found to be crucial for plasma membrane localization. HOs are located in smooth endoplasmic reticulum and colocalize with NADPH-cytochrome P450 reductase.

Conclusions
HCP1 and DMT1A-I are localized to the apical membrane, and HRG-1 to the basolateral membrane and lysosome. These findings suggest that HCP1 and DMT1A-I have functions in the uptake of dietary heme and non-heme iron. HRG-1 can transport endocytosed heme from the lysosome into the cytosol. These localization studies support a model in which cytosolic heme can be degraded by HOs, and the resulting iron is exported into tissue fluids via the iron transporter ferroportin 1, which is expressed in the basolateral membrane in enterocytes or in the plasma membrane in macrophages. The liberated iron is transported by transferrin and reutilized for hemoglobin synthesis in the erythroid system.
Identification of a novel anti-σE factor in Neisseria meningitidis
Authors: Hopman Carla Th P , Speijer Dave , van der Ende Arie , Pannekoek Yvonne 
Published: June 2010

Abstract

Background
Fine tuning expression of genes is a prerequisite for the strictly human pathogen Neisseria meningitidis to survive hostile growth conditions and establish disease. Many bacterial species respond to stress by using alternative σ factors which, in complex with RNA polymerase holoenzyme, recognize specific promoter determinants. σE, encoded by rpoE (NMB2144) in meningococci, is known to be essential in mounting responses to environmental challenges in many pathogens. Here we identified genes belonging to the σE regulon of meningococci.

Results
We show that meningococcal σE is part of the polycistronic operon NMB2140-NMB2145 and autoregulated. In addition we demonstrate that σE controls expression of methionine sulfoxide reductase (MsrA/MsrB). Moreover, we provide evidence that the activity of σE is under control of NMB2145, directly downstream of rpoE. The protein encoded by NMB2145 is structurally related to anti-sigma domain (ASD) proteins and characterized by a z inc containing a nti-σ factor (ZAS) motif, a hall mark of a specific class of Zn2+-binding ASD proteins acting as anti-σ factors. We demonstrate that Cys residues in ZAS, as well as the Cys residue on position 4, are essential for anti-σE activity of NMB2145, as found for a minority of members of the ZAS family that are predicted to act in the cytoplasm and responding to oxidative stimuli. However, exposure of cells to oxidative stimuli did not result in altered expression of σE.

Conclusions
Together, our results demonstrate that meningococci express a functional transcriptionally autoregulated σE factor, the activity of which is controlled by a novel meningococcal anti-σ factor belonging to the ZAS family.
Prevalence of the metabolic syndrome and its components in relation to socioeconomic status among Jamaican young adults: a cross-sectional study
Authors: Ferguson Trevor S , Tulloch-Reid Marshall K , Younger Novie OM , Knight-Madden Jennifer M , Samms-Vaughan Maureen , Ashley Deanna , Van den Broeck Jan , Wilks Rainford J 
Published: June 2010

Abstract

Background
The metabolic syndrome has a high prevalence in many countries and has been associated with socioeconomic status (SES). This study aimed to estimate the prevalence of the metabolic syndrome and its components among Jamaican young adults and evaluate its association with parental SES.

Methods
A subset of the participants from the 1986 Jamaica Birth Cohort was evaluated at ages 18-20 years between 2005 and 2007. Trained research nurses obtained blood pressure and anthropometric measurements and collected a venous blood sample for measurement of lipids and glucose. Prevalence of the metabolic syndrome and its components were estimated using the 2009 Consensus Criteria from the International Diabetes Federation, National Heart Lung and Blood Institute, American Heart Association, World Heart Federation, International Atherosclerosis Society, and International Association for the Study of Obesity. SES was assessed by questionnaire using occupation of household head, highest education of parent/guardian, and housing tenure of parent/guardian. Analysis yielded means and proportions for metabolic syndrome variables and covariates. Associations with levels of SES variables were obtained using analysis of variance. Multivariable analysis was conducted using logistic regression models.

Results
Data from 839 participants (378 males; 461 females) were analyzed. Prevalence of the metabolic syndrome was 1.2% (95% confidence interval [95%CI] 0.5%-1.9%). Prevalence was higher in females (1.7% vs. 0.5%). Prevalence of the components [male: female] were: central obesity, 16.0% [5.3:24.7]; elevated blood pressure, 6.7% [10.8:3.3]; elevated glucose, 1.2% [2.1:0.4]; low HDL, 46.8% [28.8:61.6]; high triglycerides, 0.6% [0.5:0.6]. There were no significant differences in the prevalence of the metabolic syndrome for any of the SES measures used possibly due to lack of statistical power. Prevalence of central obesity was inversely associated with occupation (highly skilled 12.4%, skilled 13.5%, semi-skilled/unskilled 21.8%, p = 0.013) and education (tertiary 12.5%, secondary 14.1%, primary/all-age 28.4%, p = 0.002). In sex-specific multivariate logistic regression adjusted for hip circumference, central obesity remained associated with occupation and education for women only.

Conclusion
Prevalence of the metabolic syndrome is low, but central obesity and low HDL are present in 16% and 47% of Jamaican youth, respectively. Central obesity is inversely associated with occupation and education in females.
Biotinylated-sortase self-cleavage purification (BISOP) method for cell-free produced proteins
Authors: Matsunaga Satoko , Matsuoka Kazuhiro , Shimizu Kouhei , Endo Yaeta , Sawasaki Tatsuya 
Published: June 2010

Abstract

Background
Technology used for the purification of recombinant proteins is a key issue for the biochemical and structural analyses of proteins. In general, affinity tags, such as glutathione-S-transferase or six-histidines, are used to purify recombinant proteins. Since such affinity tags often interfere negatively with the structural and functional analyses of proteins, they are usually removed by treatment with proteases. Previously, Dr. H. Mao reported self-cleavage purification of a target protein by fusing the sortase protein to its N-terminal end, and subsequently obtained tag-free recombinant protein following expression in Escherichia coli. This method, however, is yet to be applied to the cell-free based protein production.

Results
The histidine tag-based self-cleavage method for purifying proteins produced by the wheat cell-free protein synthesis system showed high background, low recovery, and unexpected cleavage between the N-terminally fused sortase and target protein during the protein synthesis. Addition of calcium chelator BAPTA to the cell-free reaction inhibited the cleavage. In order to adapt the sortase-based purification method to the cell-free system, we next used biotin as the affinity tag. The biotinylated sortase self-cleavage purification (BISOP) method provided tag-free, highly purified proteins due to improved recovery of proteins from the resin. The N-terminal sequence analysis of the GFP produced by the BISOP method revealed that the cleavage indeed occurred at the right cleavage site. Using this method, we also successfully purified the E2 heterocomplex of USE2N and USE2v1. The c-terminal src kinase (CSK) obtained by the BISOP method showed high activity in phosphorylating the Src protein. Furthermore, we demonstrated that this method is suitable for automatically synthesizing and purifying proteins using robots.

Conclusion
We demonstrated that the newly developed BISOP method is very useful for obtaining high quality, tag-free recombinant proteins, produced using the cell-free system, for biochemical and structural analyses.
Burnout in health-care professionals during reorganizations and downsizing. A cohort study in nurses
Authors: Nordang Kirsten , Hall-Lord Marie-Louise , Farup Per G 
Published: June 2010

Abstract

Background
Burnout is a psychological reaction triggered by interaction between personal characteristics and stress factors. Reorganizations and downsizing with increased workload imply stress for health-care professionals. This is a study of burnout in nurses during a period with two comprehensive reorganizations.

Methods
In this quasi-experimental retrospective cohort study, burnout was assessed in nurses with long work experience in three surveys during a 30 months' period with two comprehensive reorganizations and downsizing of a hospital unit with mostly seriously ill patients with cancer. Burnout was measured with Bergen Burnout Indicator (BBI) at each survey, and "Sense of Coherence" (SOC) with Antonovsky's questionnaire at the last survey.

Results
One man and 45 women aged 30 to 65 years were invited to the surveys. There was a significant increase in burnout during the study period, the mean increase in BBI-score was 12.5 pr year (p < 0.001). The proportion of satisfied nurses at the first and last survey were 84% and 35% respectively, and the proportions with burnout were 0% and 29% respectively (p < 0.001). Except for auxiliary nurses with experience from the medical department, all subgroups experienced a significant increase in BBI. Burnout was associated with low SOC (p < 0.001, r square 0.33).

Conclusions
There was a significant development of burnout in a group of nurses during a period with two reorganizations and downsizing. Burnout was associated with low SOC. Working with seriously ill patients with cancer has probably made the nurses exceptionally vulnerable to the stress and workload related to the reorganizations.
Use of HRP-2-based rapid diagnostic test for Plasmodium falciparum malaria: assessing accuracy and cost-effectiveness in the villages of Dielmo and Ndiop, Senegal
Authors: Ly Alioune Badara , Tall Adama , Perry Robert , Baril Laurence , Badiane Abdoulaye , Faye Joseph , Rogier Christophe , Touré Aissatou , Sokhna Cheikh , Trape Jean-François , Michel Rémy 
Published: June 2010

Abstract

Background
In 2006, the Senegalese National Malaria Control Programme (NMCP) has recommended artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria and, in 2007, mandated testing for all suspected cases of malaria with a Plasmodium falciparum HRP-2-based rapid diagnostic test for malaria (RDT(Paracheck®). Given the higher cost of ACT compared to earlier anti-malarials, the objectives of the present study were i) to study the accuracy of Paracheck® compared to the thick blood smear (TBS) in two areas with different levels of malaria endemicity and ii) analyse the cost-effectiveness of the strategy of the parasitological confirmation of clinically suspected malaria cases management recommended by the NMCP.

Methods
A cross-sectional study was undertaken in the villages of Dielmo and Ndiop (Senegal) nested in a cohort study of about 800 inhabitants. For all the individuals consulting between October 2008 and January 2009 with a clinical diagnosis of malaria, a questionnaire was filled and finger-prick blood samples were taken both for microscopic examination and RDT. The estimated costs and cost-effectiveness analysis were made considering five scenarios, the recommendations of the NMCP being the reference scenario. In addition, a sensitivity analysis was performed assuming that all the RDT-positive patients and 50% of RDT-negative patients were treated with ACT.

Results
A total of 189 consultations for clinically suspected malaria occurred during the study period. The sensitivity, specificity, positive and negative predictive values were respectively 100%, 98.3%, 80.0% and 100%. The estimated cost of the reference scenario was close to 700€ per 1000 episodes of illness, approximately twice as expensive as most of the other scenarios. Nevertheless, it appeared to us cost-effective while ensuring the diagnosis and the treatment of 100% of malaria attacks and an adequate management of 98.4% of episodes of illness. The present study also demonstrated that full compliance of health care providers with RDT results was required in order to avoid severe incremental costs.

Conclusions
A rational use of ACT requires laboratory testing of all patients presenting with presumed malaria. Use of RDTs inevitably has incremental costs, but the strategy associating RDT use for all clinically suspected malaria and prescribing ACT only to patients tested positive is cost-effective in areas where microscopy is unavailable.
MicroRNA-101 negatively regulates Ezh2 and its expression is modulated by androgen receptor and HIF-1α/HIF-1β
Authors: Cao Paul , Deng Zhiyong , Wan Meimei , Huang Weiwei , Cramer Scott D , Xu Jianfeng , Lei Ming , Sui Guangchao 
Published: June 2010

Abstract

Background
In prostate cancer (PCa), the common treatment involving androgen ablation alleviates the disease temporarily, but results in the recurrence of highly aggressive and androgen-independent metastatic cancer. Therefore, more effective therapeutic approaches are needed. It is known that aberrant epigenetics contributes to prostate malignancy. Unlike genetic changes, these epigenetic alterations are reversible, which makes them attractive targets in PCa therapy to impede cancer progression. As a histone methyltransferease, Ezh2 plays an essential role in epigenetic regulation. Since Ezh2 is overexpressed and acts as an oncogene in PCa, it has been proposed as a bona fide target of PCa therapy. MicroRNAs (miRNAs) regulate gene expression through modulating protein translation. Recently, the contribution of miRNAs in cancer development is increasingly appreciated. In this report, we present our study showing that microRNA-101 (miR-101) inhibits Ezh2 expression and differentially regulates prostate cancer cells. In addition, the expression of miR-101 alters upon androgen treatment and HIF-1α/HIF-1β induction.

Result
In our reporter assays, both miR-101 and miR-26a inhibit the expression of a reporter construct containing the 3'-UTR of Ezh2. When ectopically expressed in PC-3, DU145 and LNCaP cells, miR-101 inhibits endogenous Ezh2 expression in all three cell lines, while miR-26a only decreases Ezh2 in DU145. Ectopic miR-101 reduces the invasion ability of PC-3 cells, while restored Ezh2 expression rescues the invasiveness of PC-3 cells. Similarly, miR-101 also inhibits cell invasion and migration of DU145 and LNCaP cells, respectively. Interestingly, ectopic miR-101 exhibits differential effects on the proliferation of PC-3, DU-145 and LNCaP cells and also causes morphological changes of LNCaP cells. In addition, the expression of miR-101 is regulated by androgen receptor and HIF-1α/HIF-1β. While HIF-1α/HIF-1β induced by deferoxamine mesylate (DFO) decreases miR-101 levels, the overall effects of R-1881 on miR-101 expression are stimulatory.

Conclusions
This study indicates that miR-101 targets Ezh2 and decreases the invasiveness of PCa cells, suggesting that miR-101 introduction is a potential therapeutic strategy to combat PCa. MiR-101 differentially regulates prostate cell proliferation. Meanwhile, the expression of miR-101 is also modulated at different physiological conditions, such as androgen stimulation and HIF-1α/HIF-1β induction.