bluuebunny/crossref_metadata_2025 huggingface dataset:
Does a ‘Singing Together Group’ improve the quality of life of people with a dementia and their carers? A pilot evaluation study
Authors: Camic Paul M , Williams Caroline Myferi , Meeten Frances
Published: November 2011

Ten people with dementia (PWD) and their family carers participated in a Singing Together Group for 10 weeks and measures of mood, quality of life, PWD's behavioural and psychological problems, activities of daily living and cognitive status were measured at pre, post and 10-week follow-up. Engagement levels were monitored during the sessions and care partners asked to rate each session. Additional qualitative information was obtained through interview pre-post and at follow-up and subjected to thematic analysis. The results showed that PWD were deteriorating slowly over the course of the study on all measures but that they and their carers’ quality of life remained relatively stable. Engagement levels during the group were very high and attendance excellent. Qualitative data gave strong support to the group having promoted wellbeing of all participants and Nolan's ‘Senses Framework’ was used to explore this further. Future research directions are suggested.
Task Types and Team-Level Attributes
Authors: Wildman Jessica L. , Thayer Amanda L. , Rosen Michael A. , Salas Eduardo , Mathieu John E. , Rayne Sara R.
Published: November 2011

Within team research, there is no shortage of literature classifying teams. However, the team taxonomic literature suffers from a few limitations. First, many taxonomies claim to classify teams into mutually exclusive classes, yet when examined closely, are not. Second, some of the most well-known taxonomies are descriptive of various tasks teams engage in, but not of the holistic team-level properties that define different types of teams. A clear understanding of both is necessary if human resource development (HRD) professionals are to develop and train different teams effectively. Therefore, the purpose of the current article is twofold: to present an integrative taxonomy of task types and a set of team-level characteristics that have been carefully synthesized from the prior literature and to explain how these tools can be used in conjunction to inform team-oriented HRD research and practice.
Integrated system reliability and productive capacity analysis of a production line. A case study for a Chilean mining process
Authors: Viveros P , Zio E , Kristjanpoller F , Arata A
Published: November 2011

The analysis of a production line requires the consideration of its reliability and productive capacity since they have a direct influence on the expected levels of performance. These factors have an intrinsic stochastic behaviour which must be accounted for in the analysis. This paper proposes an integrated approach based on Monte Carlo simulation which is tested on a case study concerning the production line of a private mining company located in northern Chile. Specifically, the primary, secondary, and tertiary crushing processes are analysed in detail. Actual maintenance and operation data for 16 months of operation are considered in the case study. A tailored simulation model is developed that is able to jointly estimate the reliability and productivity of the process. The integration of these two aspects allows situations in which equipment becomes unavailable to be identified and this can improve business continuity and process productivity.
Burn-in via shocks for avoiding large risks
Authors: Cha J H , Finkelstein M
Published: November 2011

Burn-in is usually performed for items that have decreasing or bathtub failure rates in order to eliminate early failures. This can be done in either the normal environment or an accelerated environment that uses high environmental stresses, which are often referred to as shocks. Mixtures of distributions present a useful survival model for lifetime distributions in heterogeneous populations. They often result in decreasing failure rates in some time intervals, which can often justify the implementation of the burn-in procedure. This paper considers shocks that eliminate weak items in heterogeneous populations. It is assumed that a larger failure rate of an item corresponds to a larger probability of this elimination. Approaches are developed that can help to minimize the risks of selecting items with large levels of individual failure rates for missions of high importance, where failures can result in substantial economic losses. The optimal burn-in time which minimizes average losses for different criteria is considered using simple examples.
Fever induction by systemic stimulation with macrophage-activating lipopeptide-2 depends upon TLR2 but not CD36
Authors: Welsch Janina , Hübschle Thomas , Murgott Jolanta , Kirschning Carsten , Rummel Christoph , Gerstberger Rüdiger , Roth Joachim
Published: November 2011

This study was designed to test the responses of TLR2-knockout mice (TLR2-KO) and wild- type mice (C57/BL-6), and of CD36 deficient spontaneously hypertensive rats (SHR) and their genetic controls [Wistar Kyoto (WKY) rats] to systemic stimulations with the TLR2/6 agonist MALP-2 and the TLR4 agonist LPS. Fever and formation of TNF-α and IL-6 induced by intraperitoneal injections of MALP-2 (1000 µg/kg) were completely blunted in TLR2-KO, while LPS (100 µg/kg)-induced responses were not abolished in these animals. In SHR lacking CD36, a reduction of fever was observed in response to MALP-2 (100 µg/kg), but LPS-fever was even more attenuated in SHR when compared with WKY controls. Concentrations of circulating IL-6 tended to be lower in SHR after stimulation with both pyrogens. However, the IL-6-mediated activation of the transcription factor STAT3 in the brain was identical in both strains, indicating that the brain-controlled inflammatory response to MALP-2 (and LPS) is not impaired in the absence of CD36. In addition, stimulation of peritoneal macrophages with LPS and MALP-2 (10 µg/ml) caused the appearance of similar concentrations of bioactive cytokines in the supernatants from cells of both rat strains. These results demonstrate that TLR2 is essential for the manifestation of MALP-2, but not LPS-induced inflammatory responses. A moderate participation of CD36 in MALP-2-induced sickness- and cytokine-responses can not be ruled out but is unlikely as LPS-induced inflammatory responses were also attenuated in SHR.
Cellular resistance to HIV-1 infection in target cells coincides with a rapid induction of X-DING-CD4 mRNA: Indication of the unique host innate response to virus regulated through function of the X-DING-CD4 gene
Authors: Shilpi Rasheda Y , Sachdeva Rakhee , Simm Malgorzata
Published: November 2011

Clinical reports indicate that some infected individuals control HIV-1 replication through undefined mechanisms. Our group reported that a human protein named X-DING-CD4 holds a potent antiviral activity, blocking transcription of HIV-1 LTR through the inhibition of NF-κB/DNA binding. Based on observations that transformed HIV-1 resistant CD4+ T cells produce higher levels of soluble X-DING-CD4 protein upon their exposure to virus, we hypothesized that resistance to HIV-1 in these cells may be regulated through function of the X-DING-CD4 gene. Real-time PCR evaluations of X-DING-CD4 mRNA expression confirmed our hypothesis; HIV-1 exposure caused rapid up-regulation of X-DING-CD4 mRNA in resistant, but not susceptible, cells; and the burst of X-DING-CD4 mRNA expression correlated with restriction of HIV-1 transcription. Subsequently, we examined the activity of the X-DING-CD4 gene in monocytes and macrophages from ( n = 13) HIV-negative donors. The assessment of HIV-1 gag mRNA showed that the majority of cells were permissive to virus replication; however, macrophages from four donors were refractory to HIV-1 infection. In response to virus, these cells up-regulated X-DING-CD4 gene expression by 2- to 1000-fold. These data provide evidence that the X-DING-CD4 gene contributes to early cellular protection from HIV infection in some individuals and this protection depends solely on the unique genetic regulation of the host.
Future directions in the evaluation of c-MET-driven malignancies
Authors: de Bono Johann S. , Yap Timothy A.
Published: November 2011

The c-MET (mesenchymal–epithelial transition factor) receptor tyrosine kinase is an exciting novel drug target in view of its key role in oncogenesis, as well as its association with disease prognosis in a number of malignancies. Several drugs targeting c-MET are currently showing promise in clinical trials and will hopefully validate positive observations from preclinical studies. The potential efficacy of these different therapeutic agents is expected to be influenced by the mechanism of aberrant hepatocyte growth factor (HGF)/c-MET signaling pathway activation in a particular cancer, but presents a promising strategy for cancer treatment either as a single agent or as part of a combination therapeutic approach. However, there is an ongoing need to improve and accelerate the transition of preclinical research into improved therapeutic strategies for patients with cancer. The main challenges facing the development of HGF/c-MET-targeted agents for cancer treatment include the discovery of rationally designed anticancer drugs and combination strategies, as well as the validation of predictive biomarkers. This paper discusses these issues, with a particular focus on future directions in the evaluation of c-MET-driven malignancies.
Selective Expansion of CD34+ Cells from Mouse Bone Marrow Cultured on LH/P MP-Coated Plates with Adequate Cytokines
Authors: Kishimoto Satoko , Ishihara Masayuki , Kanatani Yasuhiro , Nambu Masaki , Takikawa Megumi , Sumi Yuki , Nakamura Shingo , Mori Yasutaka , Hattori Hidemi , Tanaka Yoshihiro , Sato Toshinori
Published: November 2011

Low-molecular-weight heparin/protamine microparticles (LH/P MPs) serve as carriers for controlled release of heparin-binding cytokines. LH/P MPs were stably coated onto plastic surfaces by drying. The purpose of this study is to evaluate a culture method for selective expansion of CD34+ cells using LH/P MPs as cytokine-binding matrix. Ficoll-purified mouse bone marrow cells (mouse FP-BMCs) containing CD34+ cells were cultured on LH/P MP-coated plates in the presence of stem cell factor (SCF), thrombopoietin (Tpo), and Flt-3 ligand (Flt-3) in hematopoietic progenitor growth medium (HPGM) supplemented with 4% heat-inactivated fetal bovine serum (FBS). After 8 days of culture, the total cell count increased 4.6-fold, and flow cytometry analyses revealed that 23.8% of the initial cells and 57.4% of the expanded cells were CD34 positive. Therefore, CD34+ cells were estimated to have increased 11.0-fold. In contrast, cultured CD34+ cells on uncoated tissue culture plates increased 5.8-fold in an identical medium.
In situ vaccination against mycosis fungoides by intratumoral injection of a TLR9 agonist combined with radiation: a phase 1/2 study
Authors: Kim Youn H. , Gratzinger Dita , Harrison Cameron , Brody Joshua D. , Czerwinski Debra K. , Ai Weiyun Z. , Morales Anjali , Abdulla Farah , Xing Leon , Navi Daniel , Tibshirani Robert J. , Advani Ranjana H. , Lingala Bharathi , Shah Sumit , Hoppe Richard T. , Levy Ronald
Published: November 2011

We have developed and previously reported on a therapeutic vaccination strategy for indolent B-cell lymphoma that combines local radiation to enhance tumor immunogenicity with the injection into the tumor of a TLR9 agonist. As a result, antitumor CD8+ T cells are induced, and systemic tumor regression was documented. Because the vaccination occurs in situ, there is no need to manufacture a vaccine product. We have now explored this strategy in a second disease: mycosis fungoides (MF). We treated 15 patients. Clinical responses were assessed at the distant, untreated sites as a measure of systemic antitumor activity. Five clinically meaningful responses were observed. The procedure was well tolerated and adverse effects consisted mostly of mild and transient injection site or flu-like symptoms. The immunized sites showed a significant reduction of CD25+, Foxp3+ T cells that could be either MF cells or tissue regulatory T cells and a similar reduction in S100+, CD1a+ dendritic cells. There was a trend toward greater reduction of CD25+ T cells and skin dendritic cells in clinical responders versus nonresponders. Our in situ vaccination strategy is feasible also in MF and the clinical responses that occurred in a subset of patients warrant further study with modifications to augment these therapeutic effects. This study is registered at www.clinicaltrials.gov as NCT00226993.
FTY720 increases CD74 expression and sensitizes mantle cell lymphoma cells to milatuzumab-mediated cell death
Authors: Alinari Lapo , Mahoney Emilia , Patton John , Zhang Xiaoli , Huynh Lenguyen , Earl Christian T. , Mani Rajeswaran , Mao Yicheng , Yu Bo , Quinion Carl , Towns William H. , Chen Ching-Shih , Goldenberg David M. , Blum Kristie A. , Byrd John C. , Muthusamy Natarajan , Prætorius-Ibba Mette , Baiocchi Robert A.
Published: November 2011

Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy with a short median survival despite multimodal therapy. FTY720, an immunosuppressive drug approved for the treatment of multiple sclerosis, promotes MCL cell death concurrent with down-modulation of phospho-Akt and cyclin D1 and subsequent cell-cycle arrest. However, the mechanism of FTY720-mediated MCL cell death remains to be fully clarified. In the present study, we show features of autophagy blockage by FTY720 treatment, including accumulation of autolysosomes and increased LC3-II and p62 levels. We also show that FTY720-induced cell death is mediated by lysosomal membrane permeabilization with subsequent translocation of lysosomal hydrolases to the cytosol. FTY720-mediated disruption of the autophagic-lysosomal pathway led to increased levels of CD74, a potential therapeutic target in MCL that is degraded in the lysosomal compartment. This finding provided rationale for examining combination therapy with FTY720 and milatuzumab, an anti-CD74 mAb. Treatment of MCL cell lines and primary tumor cells with FTY720 and milatuzumab resulted in statistically significant enhanced cell death, which was synergistic in blastic variant MCL cell lines. Significant in vivo therapeutic activity of combination treatment was also demonstrated in a preclinical, in vivo model of MCL. These findings support clinical evaluation of this combination in patients with MCL.
Population pharmacokinetics of recombinant factor VIII: the relationships of pharmacokinetics to age and body weight
Authors: Björkman Sven , Oh MyungShin , Spotts Gerald , Schroth Phillip , Fritsch Sandor , Ewenstein Bruce M. , Casey Kathleen , Fischer Kathelijn , Blanchette Victor S. , Collins Peter W.
Published: November 2011

Comparison of the pharmacokinetics (PK) of a coagulation factor between groups of patients can be biased by differences in study protocols, in particular between blood sampling schedules. This could affect clinical dose tailoring, especially in children. The aim of this study was to describe the relationships of the PK of factor VIII (FVIII) with age and body weight by a population PK model. The potential to reduce blood sampling was also explored. A model was built for FVIII PK from 236 infusions of recombinant FVIII in 152 patients (1-65 years of age) with severe hemophilia A. The PK of FVIII over the entire age range was well described by a 2-compartment model and a previously reported problem, resulting from differences in blood sampling, to compare findings from children and adults was practically abolished. The decline in FVIII clearance and increase in half-life with age could be described as continuous functions. Retrospective reduction of blood sampling from 11 to 5 samples made no important difference to the estimates of PK parameters. The obtained findings can be used as a basis for PK-based dose tailoring of FVIII in clinical practice, in all age groups, with minimal blood sampling.
Identification of common and cell type specific LXXLL motif EcR cofactors using a bioinformatics refined candidate RNAi screen in Drosophila melanogastercell lines
Authors: Davis Melissa B , SanGil Inigo , Berry Grace , Olayokun Rashidat , Neves Lori H
Published: November 2011

Background

During Drosophila development, titers of the steroid ecdysone trigger and maintain temporal and tissue specific biological transitions. Decades of evidence reveal that the ecdysone response is both unique to specific tissues and distinct among developmental timepoints. To achieve this diversity in response, the several isoforms of the Ecdysone Receptor, which transduce the hormone signal to the genome level, are believed to interact with tissue specific cofactors. To date, little is known about the identity of these cofactor interactions; therefore, we conducted a bioinformatics informed, RNAi luciferase reporter screen against a subset of putative candidate cofactors identified through an in silico proteome screen. Candidates were chosen based on criteria obtained from bioinformatic consensus of known nuclear receptor cofactors and homologs, including amino acid sequence motif content and context.

Results

The bioinformatics pre-screen of the Drosophila melanogaster proteome was successful in identifying an enriched putative candidate gene cohort. Over 80% of the genes tested yielded a positive hit in our reporter screen. We have identified both cell type specific and common cofactors which appear to be necessary for proper ecdysone induced gene regulation. We have determined that certain cofactors act as co-repressors to reduce target gene expression, while others act as co-activators to increase target gene expression. Interestingly, we find that a few of the cofactors shared among cell types have a reversible roles to function as co-repressors in certain cell types while in other cell types they serve as co-activators. Lastly, these proteins are highly conserved, with higher order organism homologs also harboring the LXXLL steroid receptor interaction domains, suggesting a highly conserved mode of steroid cell target specificity.

Conclusions

In conclusion, we submit these cofactors as novel components of the ecdysone signaling pathway in order to further elucidate the dynamics of steroid specificity.
Functional microRNA screening using a comprehensive lentiviral human microRNA expression library
Authors: Poell Jos B , van Haastert Rick J , Cerisoli Francesco , Bolijn Anne S , Timmer Lisette M , Diosdado-Calvo Begoña , Meijer Gerrit A , van Puijenbroek Andre AFL , Berezikov Eugene , Schaapveld Roel QJ , Cuppen Edwin
Published: November 2011

Background

MicroRNAs (miRNAs) are a class of small regulatory RNAs that target sequences in messenger RNAs (mRNAs) to inhibit their protein output. Dissecting the complexities of miRNA function continues to prove challenging as miRNAs are predicted to have thousands of targets, and mRNAs can be targeted by dozens of miRNAs.

Results

To systematically address biological function of miRNAs, we constructed and validated a lentiviral miRNA expression library containing 660 currently annotated and 422 candidate human miRNA precursors. The miRNAs are expressed from their native genomic backbone, ensuring physiological processing. The arrayed layout of the library renders it ideal for high-throughput screens, but also allows pooled screening and hit picking. We demonstrate its functionality in both short- and long-term assays, and are able to corroborate previously described results of well-studied miRNAs.

Conclusions

With the miRNA expression library we provide a versatile tool for the systematic elucidation of miRNA function.
Comparing Enterovirus 71 with Coxsackievirus A16 by analyzing nucleotide sequences and antigenicity of recombinant proteins of VP1s and VP4s
Authors: Li Yuyun , Zhu Runan , Qian Yuan , Deng Jie , Sun Yu , Liu Liying , Wang Fang , Zhao Linqing
Published: November 2011

Background

Enterovirus 71 (EV71) and Coxsackievirus A16 (CA16) are two major etiological agents of Hand, Foot and Mouth Disease (HFMD). EV71 is associated with severe cases but not CA16. The mechanisms contributed to the different pathogenesis of these two viruses are unknown. VP1 and VP4 are two major structural proteins of these viruses, and should be paid close attention to.

Results

The sequences of vp1s from 14 EV71 and 14 CA16, and vp4s from 10 EV71 and 1 CA16 isolated in this study during 2007 to 2009 HFMD seasons were analyzed together with the corresponding sequences available in GenBank using DNAStar and MEGA 4.0. Phylogenetic analysis of complete vp1s or vp4s showed that EV71 isolated in Beijing belonged to C4 and CA16 belonged to lineage B2 (lineage C). VP1s and VP4s from 4 strains of viruses expressed in E. coli BL21 cells were used to detect IgM and IgG in human sera by Western Blot. The detection of IgM against VP1s of EV71 and CA16 showed consistent results with current infection, while none of the sera were positive against VP4s of EV71 and CA16. There was significant difference in the positive rates between EV71 VP1 and CA16 VP1 (χ2 = 5.02, P < 0.05) as well as EV71 VP4 and CA16 VP4 (χ2 = 15.30, P < 0.01) in the detection of IgG against recombinant proteins with same batch of serum samples. The sera-positive rate of IgG against VP1 was higher than that against VP4 for both EV71 (χ2 = 26.47, P < 0.01) and CA16 (χ2 = 16.78, P < 0.01), which might be because of different positions of VP1 and VP4 in the capsid of the viruses.

Conclusions

EV71 and CA16 were highly diverse in the nucleotide sequences of vp1s and vp4s. The sera positive rates of VP1 and VP4 of EV71 were lower than those of CA16 respectively, which suggested a less exposure rate to EV71 than CA16 in Beijing population. Human serum antibodies detected by Western blot using VP1s and VP4s as antigen indicated that the immunological reaction to VP1 and VP4 of both EV71 and CA16 was different.
Identification of a myometrial molecular profile for dystocic labor
Authors: Brennan Donal J , McGee Sharon F , Rexhepaj Elton , O'Connor Darran P , Robson Michael , O'Herlihy Colm
Published: November 2011

Background

The most common indication for cesarean section (CS) in nulliparous women is dystocia secondary to ineffective myometrial contractility. The aim of this study was to identify a molecular profile in myometrium associated with dystocic labor.

Methods

Myometrial biopsies were obtained from the upper incisional margins of nulliparous women undergoing lower segment CS for dystocia (n = 4) and control women undergoing CS in the second stage who had demonstrated efficient uterine action during the first stage of labor (n = 4). All patients were in spontaneous (non-induced) labor and had received intrapartum oxytocin to accelerate labor. RNA was extracted from biopsies and hybridized to Affymetrix HuGene U133A Plus 2 microarrays. Internal validation was performed using quantitative SYBR Green Real-Time PCR.

Results

Seventy genes were differentially expressed between the two groups. 58 genes were down-regulated in the dystocia group. Gene ontology analysis revealed 12 of the 58 down-regulated genes were involved in the immune response. These included (ERAP2, (8.67 fold change (FC)) HLA-DQB1 (7.88 FC) CD28 (2.60 FC), LILRA3 (2.87 FC) and TGFBR3 (2.1 FC)) Hierarchical clustering demonstrated a difference in global gene expression patterns between the samples from dystocic and non-dystocic labours. RT-PCR validation was performed on 4 genes ERAP2, CD28, LILRA3 and TGFBR3

Conclusion

These findings suggest an underlying molecular basis for dystocia in nulliparous women in spontaneous labor. Differentially expressed genes suggest an important role for the immune response in dystocic labor and may provide important indicators for new diagnostic assays and potential intrapartum therapeutic targets.
Light triggered detection of aminophenyl phosphate with a quantum dot based enzyme electrode
Authors: Khalid Waqas , Göbel Gero , Hühn Dominik , Montenegro Jose-Maria , Rivera-Gil Pilar , Lisdat Fred , Parak Wolfgang J
Published: November 2011

An electrochemical sensor for p-aminophenyl phosphate (p APP) is reported. It is based on the electrochemical conversion of 4-aminophenol (4AP) at a quantum dot (QD) modified electrode under illumination. Without illumination no electron transfer and thus no oxidation of 4AP can occur. p APP as substrate is converted by the enzyme alkaline phosphatase (ALP) to generate 4AP as a product. The QDs are coupled via 1,4-benzenedithiol (BDT) linkage to the surface of a gold electrode and thus allow potential-controlled photocurrent generation. The photocurrent is modified by the enzyme reaction providing access to the substrate detection. In order to develop a photobioelectrochemical sensor the enzyme is immobilized on top of the photo-switchable layer of the QDs. Immobilization of ALP is required for the potential possibility of spatially resolved measurements. Geometries with immobilized ALP are compared versus having the ALP in solution. Data indicate that functional immobilization with layer-by-layer assembly is possible. Enzymatic activity of ALP and thus the photocurrent can be described by Michaelis- Menten kinetics. p APP is detected as proof of principle investigation within the range of 25 μM - 1 mM.
The prevalence of idiopathic hirsutism and polycystic ovary syndrome in the Tehran Lipid and Glucose Study
Authors: Tehrani Fahimeh Ramezani , Rashidi Homeira , Azizi Fereidoun
Published: November 2011

Background

There is no clear and contemporaneous method for screening of idiopathic hirsutism (IH) and polycystic ovary syndrome (PCOS) at the community level and current estimates regarding their prevalence are limited. We aimed to ascertain the prevalence of IH and PCOS in a randomly selected sample of reproductive aged female participants of the Tehran Lipid and Glucose Study (TLGS).

Methods

One thousand and two women, aged 18-45 years, were randomly selected from among reproductive aged women who participated in the TLGS. Those women with either hirsutism or menstrual dysfunction were assessed for biochemical hyperandrogenemia; whereas those participants with hirsutism per se were further assessed for subclinical menstrual dysfunction. PCOS were diagnosed using the National Institute of Health (NIH) criteria. IH was defined as hirsutism without clinical or sub clinical menstrual dysfunction or biochemical hyperandrogenemia (BH).

Results

The mean ± SD of age of study population was 29.2 ± 8.7 years. Estimated prevalences of idiopathic hirsutism and pure menstrual dysfunction were 13.0% (95% CI: 10.9%-15.1%) and 1.5%(95% CI: 1.1%-1.9%), respectively. The prevalence of PCOS was 8.5% (95% CI: 6.8% - 10.2%); more than one third of these cases would possibly have remained undiagnosed or misdiagnosed, had we not assessed them for subclinical menstrual dysfunction or biochemical hyperandrogenemia.

Conclusions

These data from a large representative and non selected population of women confirm the concept that IH and PCOS are the two most common gynecological endocrinopathies among reproductive aged women. The estimated prevalence of these conditions is highly influenced by their screening methods at the community level.
Sex differences in the morphological failure patterns following hip resurfacing arthroplasty
Authors: Hinsch Andrea , Vettorazzi Eik , Morlock Michael M , Rüther Wolfgang , Amling Michael , Zustin Jozef
Published: November 2011

Background

Metal-on-metal hybrid hip resurfacing arthroplasty (with a cementless acetabular component and a cemented femoral component) is offered as an alternative to traditional total hip arthroplasty for the young and active adult with advanced osteoarthritis. Although it has been suggested that women are less appropriate candidates for metal-on-metal arthroplasty, the mechanisms of prosthesis failure has not been fully explained. While specific failure patterns, particularly osteonecrosis and delayed type hypersensitivity reactions have been suggested to be specifically linked to the sex of the patient, we wished to examine the potential influence of sex, clinical diagnosis, age of the patient and the size of the femoral component on morphological failure patterns in a large cohort of retrieved specimens following aseptic failure of hip resurfacing arthroplasty.

Methods

Femoral remnants retrieved from 173 hips with known patient's sex were morphologically analyzed for the cause of failure. The results were compared with the control group of the remaining 31 failures from patients of unknown sex. The odds ratios (OR) and 95% confidence intervals (CI) of the following morphologically defined variables were calculated using logistic regression analysis: periprosthetic fractures (n = 133), osteonecrosis (n = 151), the presence of excessive intraosseous lymphocyte infiltration (n = 11), and interface hyperosteoidosis (n = 30). Logistic regression analysis was performed both unadjusted and after adjustment for sex, age, the size of the femoral component, and preoperative clinical diagnosis.

Results

Femoral remnants from female patients had a smaller OR for fracture (adjusted OR: 0.29, 95% CI 0.11, 0.80, P for difference = 0.02) and for the presence of osteonecrosis (adjusted OR: 0.16, 95% CI 0.04, 0.63, P for difference = 0.01). However, women had a higher OR for both the presence of excessive intraosseous lymphocyte infiltration (adjusted OR: 10.22, 95% CI 0.79, 132.57, P for difference = 0.08) and interface hyperosteoidosis (adjusted OR: 4.19, 95% CI 1.14, 15.38, P for difference = 0.03).

Conclusions

Within the limitations of this study, we demonstrated substantial sex differences in distinct failure patterns of metal-on-metal hip resurfacing. Recognition of pathogenically distinct failure modes will enable further stratification of risk factors for certain failure mechanisms and thus affect future therapeutic options for selected patient groups.
Characteristics of epstein barr virus variants associated with gastric carcinoma in Southern Tunisia
Authors: BenAyed-Guerfali Dorra , Ayadi Wajdi , Miladi-Abdennadher Imen , Khabir Abdelmajid , Sellami-Boudawara Tahia , Gargouri Ali , Mokdad-Gargouri Raja
Published: November 2011

Backgroud

EBV-associated Gastric Carcinoma (EBVaGC) has a distinct clinical features and its prevalence is variable worldwide.

Results

To determine the prevalence of EBVaGC in Tunisia, EBV-encoded small RNA (EBER) expression was assessed in 81 gastric carcinoma (GC) specimens. The nuclear EBER expression was detected in 12 out of 81 GC cases (14.81%) and concordance between the score range of EBER staining and the number of EBV DNA copies as estimate by QPCR is observed. On the other hand, we found that EBVaGC strongly correlated with age at diagnosis, and weakly with tumor differentiation and venous invasion.

Furthermore, the EBVaGC specimens were subjected to determine the EBV DNA polymorphisms. Our results show a unique genetic profile of the EBV strains regarding the A and D types, the F prototype, the retention of Xho I restriction site and the 30 bp del-LMP1 variant.
According to our previous studies on nasopharyngeal carcinoma (NPC), we suggested that EBV strains associated to GC and NPC shared some similarities in Tunisian patients

.

Conclusion

The prevalence of EBVaGC is of 14.81% in the southern Tunisia and that common EBV strain are associated with both NPC and GC which are likely to differ from Asian strains. Our findings support therefore a certain geographical distribution of EBV strains which is not restricted to EBV-associated malignancies.
Molecular detection of Torque teno virus in different breeds of swine
Authors: Wu Zhiwei , Wang Hongning , Yang Xin , Guan Zhongbing , Zhou Yingshun
Published: November 2011

Background

Torque teno virus (TTV), of the Anelloviridae family, Iotatorquevirus genus, is a non-enveloped, single-stranded, and negative sense DNA (ssDNA) virus infecting human and many domestic animals including swines. Very little information is known about the investigations of TTV prevalence in different swine breeds so far.

Methods

In this study, 208 serum samples collected from seven swine breeds (Rongchang pig, Chenghua pig, Zibet pig, Wild boar, Duroc, Landrace, Large Yorkshire) from two independent farms were detected to determine the prevalence of two swine TTV genogroups, TTV1 and TTV 2, by nested polymerase chain reaction methods, and to analyse prevalence difference among these breeds.

Results

The results showed that the prevalence of TTV in the seven breeds was 92%-100%. No significant difference (p > 0.05) in TTV infection was observed between different breeds. Interestingly, significantly higher prevalence for TTV1 in Rongchang boars (90%) and for TTV2 in Rongchang sows (95%) were detected, while co-infection rate (43.8%) was lower than other breeds. Sequence analysis showed that the homology of TTV1 and TTV2 were over 90.9% and 86.4% in these breeds, respectively.

Conclusions

The results indicated that TTV was widely distributed in the seven swine breeds. The prevalence of both TTV genogroups associated with swine breeds and genders. This study also respented the first description of swine TTV prevalence in different swine breeds. It was vitally necessary to further study swine TTV pathogenicity.
Combined STN/SNr-DBS for the treatment of refractory gait disturbances in Parkinson's disease: study protocol for a randomized controlled trial
Authors: Weiss Daniel , Wächter Tobias , Meisner Christoph , Fritz Melanie , Gharabaghi Alireza , Plewnia Christian , Breit Sorin , Krüger Rejko
Published: November 2011

Background

Severe gait disturbances in idiopathic Parkinson's disease (PD) are observed in up to 80% of all patients in advanced disease stages with important impact on quality of life. There is an unmet need for further symptomatic therapeutic strategies, particularly as gait disturbances generally respond unfavourably to dopaminergic medication and conventional deep brain stimulation of the subthalamic nucleus in advanced disease stages. Recent pathophysiological research pointed to nigro-pontine networks entrained to locomotor integration. Stimulation of the pedunculopontine nucleus is currently under investigation, however, hitherto remains controversial. The substantia nigra pars reticulata (SNr) - entrained into integrative locomotor networks - is pathologically overactive in PD. High-frequent stimulation of the substantia nigra pars reticulata preferentially modulated axial symptoms and therefore is suggested as a novel therapeutic candidate target for neuromodulation of refractory gait disturbances in PD.

Methods

12 patients with idiopathic Parkinson's disease and refractory gait disturbances under best individual subthalamic nucleus stimulation and dopaminergic medication will be enroled into this double-blind 2 × 2 cross-over clinical trial. The treatment consists of two different stimulation settings using (i) conventional stimulation of the subthalamic nucleus [STNmono] and (ii) combined stimulation of distant electrode contacts located in the subthalamic nucleus and caudal border zone of STN and substantia nigra pars reticulata [STN+SNr]. The primary outcome measure is the change of the cumulative 'axial score' (UPDRS II items '13-15' and UPRDS III items '27-31') at three weeks of constant stimulation in either condition. Secondary outcome measures include specific scores on freezing of gait, balance function, quality of life, non-motor symptoms, and neuropsychiatric symptoms. The aim of the present trial is to investigate the efficacy and safety of a three week constant combined stimulation on [STN+SNr] compared to [STNmono]. The results will clarify, whether stimulation on nigral contacts additional to subthalamic stimulation will improve therapeutic response of otherwise refractory gait disturbances in PD.

Trial registration

The trial was registered with the clinical trials register of http://www.clinicaltrials.gov (NCT01355835)
Correlation between DNA ploidy, metaphase high-resolution comparative genomic hybridization results and clinical outcome of synovial sarcoma
Authors: Balogh Zsófia , Szemlaky Zsuzsanna , Szendrői Miklós , Antal Imre , Pápai Zsuzsanna , Fónyad László , Papp Gergő , Changchien Yi C , Sápi Zoltán
Published: November 2011

Background

Although synovial sarcoma is the 3rd most commonly occurring mesenchymal tumor in young adults, usually with a highly aggressive clinical course; remarkable differences can be seen regarding the clinical outcome. According to comparative genomic hybridization (CGH) data published in the literature, the simple and complex karyotypes show a correlation between the prognosis and clinical outcome. In addition, the connection between DNA ploidy and clinical course is controversial. The aim of this study was using a fine-tuning interpretation of our DNA ploidy results and to compare these with metaphase high-resolution CGH (HR-CGH) results.

Methods

DNA ploidy was determined on Feulgen-stained smears in 56 synovial sarcoma cases by image cytometry; follow up was available in 46 cases (average: 78 months). In 9 cases HR-CGH analysis was also available.

Results

10 cases were found DNA-aneuploid, 46 were DNA-diploid by image cytometry. With fine-tuning of the diploid cases according to the 5c exceeding events (single cell aneuploidy), 33 cases were so called "simple-diploid" (without 5c exceeding events) and 13 cases were "complex-diploid"; containing 5c exceeding events (any number). Aneuploid tumors contained large numbers of genetic alterations with the sum gain of at least 2 chromosomes (A-, B- or C-group) detected by HR-CGH. In the "simple-diploid" cases no or few genetic alterations could be detected, whereas the "complex-diploid" samples numerous aberrations (equal or more than 3) could be found.

Conclusions

Our results show a correlation between the DNA-ploidy, a fine-tuned DNA-ploidy and the HR-CGH results. Furthermore, we found significant correlation between the different ploidy groups and the clinical outcome (p < 0.05).
Loop-mediated isothermal amplification (LAMP) assays for the species-specific detection of Eimeria that infect chickens
Authors: Barkway Christopher P , Pocock Rebecca L , Vrba Vladimir , Blake Damer P
Published: November 2011

Background

Eimeria parasites can cause the disease coccidiosis in poultry and even subclinical infection can incur economic loss. Diagnosis of infection predominantly relies on traditional techniques including lesion scoring and faecal microscopy despite the availability of sensitive molecular assays, largely due to cost and the requirement for specialist equipment. Despite longstanding proven efficacy these traditional techniques demand time and expertise, can be highly subjective and may under-diagnose subclinical disease. Recognition of the tight economic margins prevailing in modern poultry production and the impact of avian coccidiosis on poverty in many parts of the world has highlighted a requirement for a panel of straightforward and sensitive, but cost-effective, Eimeria species-specific diagnostic assays.

Results

Loop-mediated isothermal amplification (LAMP) is an uncomplicated, quick and relatively inexpensive diagnostic tool. In this study we have developed a panel of species-specific LAMP assays targeting the seven Eimeria species that infect the chicken. Each assay has been shown to be genuinely species-specific with the capacity to detect between one and ten eimerian genomes, equivalent to less than a single mature schizont. Development of a simple protocol for template DNA preparation from tissue collected post mortem with no requirement for specialist laboratory equipment supports the use of these assays in routine diagnosis of eimerian infection. Preliminary field testing supports this hypothesis.

Conclusions

Development of a panel of sensitive species-specific LAMP assays introduces a valuable new cost-effective tool for use in poultry husbandry.
Gene expression profiles of breast biopsies from healthy women identify a group with claudin-low features
Authors: Haakensen Vilde D , Lingjærde Ole Christian , Lüders Torben , Riis Margit , Prat Aleix , Troester Melissa A , Holmen Marit M , Frantzen Jan Ole , Romundstad Linda , Navjord Dina , Bukholm Ida K , Johannesen Tom B , Perou Charles M , Ursin Giske , Kristensen Vessela N , Børresen-Dale Anne-Lise , Helland Åslaug
Published: November 2011

Background

Increased understanding of the variability in normal breast biology will enable us to identify mechanisms of breast cancer initiation and the origin of different subtypes, and to better predict breast cancer risk.

Methods

Gene expression patterns in breast biopsies from 79 healthy women referred to breast diagnostic centers in Norway were explored by unsupervised hierarchical clustering and supervised analyses, such as gene set enrichment analysis and gene ontology analysis and comparison with previously published genelists and independent datasets.

Results

Unsupervised hierarchical clustering identified two separate clusters of normal breast tissue based on gene-expression profiling, regardless of clustering algorithm and gene filtering used. Comparison of the expression profile of the two clusters with several published gene lists describing breast cells revealed that the samples in cluster 1 share characteristics with stromal cells and stem cells, and to a certain degree with mesenchymal cells and myoepithelial cells. The samples in cluster 1 also share many features with the newly identified claudin-low breast cancer intrinsic subtype, which also shows characteristics of stromal and stem cells. More women belonging to cluster 1 have a family history of breast cancer and there is a slight overrepresentation of nulliparous women in cluster 1. Similar findings were seen in a separate dataset consisting of histologically normal tissue from both breasts harboring breast cancer and from mammoplasty reductions.

Conclusion

This is the first study to explore the variability of gene expression patterns in whole biopsies from normal breasts and identified distinct subtypes of normal breast tissue. Further studies are needed to determine the specific cell contribution to the variation in the biology of normal breasts, how the clusters identified relate to breast cancer risk and their possible link to the origin of the different molecular subtypes of breast cancer.
Effects of DNMT1 silencing on malignant phenotype and methylated gene expression in cervical cancer cells
Authors: Zhang Yi , Chen Fu-qiang , Sun Ye-hong , Zhou Shu-yan , Li Ti-yuan , Chen Rui
Published: November 2011

Background

DNA methylation has been widely used in classification, early diagnosis, therapy and prediction of metastasis as well as recurrence of cervical cancer. DNMT methyltransferase 1 (DNMT1), which plays a significant role in maintaining DNA methylation status and regulating the expression of tumor suppressor genes. The aim of this research was to investigate the relationship between DNMT1 and abnormal methylation of tumor suppressor genes and malignant phenotype in cervical cancer.

Methods

Levels of DNMT1 mRNA and protein were detected using qPCR and Western blot, respectively. Cell proliferation was analyzed by MTT and apoptosis was performed by Annexin V-FITC/PI double staining flow cytometry, respectively. MeDIP-qPCR and qPCR were performed to measure demethylation status and mRNA re-expression level of 7 tumor-suppressor genes (CCNA1, CHFR, FHIT, PAX1, PTEN, SFRP4, TSLC1) in Hela and Siha cells after silencing DNMT1.

Results

The average expression levels of DNMT1 mRNA and protein in Hela and Siha cells were decreased significantly compared with control group. The flow cytometry and MTT results showed that Hela and Siha cells apoptosis rates and cell viabilities were 19.4 ± 2.90%, 25.7 ± 3.92% as well as 86.7 ± 3.12%, 84.16 ± 2.67% respectively 48 h after transfection (P < 0.01). Furthermore, the promoter methylation of five tumor suppressor genes was decreased with the increased mRNA expression after silencing DNMT1, whereas there were no significant changes in PTEN and FHIT genes in Hela cells, and CHFR and FHIT genes in Siha cells.

Conclusions

Our experimental results demonstrate that methylation status of DNMT1 can influence several important tumor suppressor genes activity in cervical tumorigenesis and may have the potential to become an effective target for treatment of cervical cancer.
Effects of a radiation dose reduction strategy for computed tomography in severely injured trauma patients in the emergency department: an observational study
Authors: Kim Soo Hyun , Jung Seung Eun , Oh Sang Hoon , Park Kyu Nam , Youn Chun Song
Published: November 2011

Background

Severely injured trauma patients are exposed to clinically significant radiation doses from computed tomography (CT) imaging in the emergency department. Moreover, this radiation exposure is associated with an increased risk of cancer. The purpose of this study was to determine some effects of a radiation dose reduction strategy for CT in severely injured trauma patients in the emergency department.

Methods

We implemented the radiation dose reduction strategy in May 2009. A prospective observational study design was used to collect data from patients who met the inclusion criteria during this one year study (intervention group) from May 2009 to April 2010. The prospective data were compared with data collected retrospectively for one year prior to the implementation of the radiation dose reduction strategy (control group). By comparison of the cumulative effective dose and the number of CT examinations in the two groups, we evaluated effects of a radiation dose reduction strategy. All the patients met the institutional adult trauma team activation criteria. The radiation doses calculated by the CT scanner were converted to effective doses by multiplication by a conversion coefficient.

Results

A total of 118 patients were included in this study. Among them, 33 were admitted before May 2009 (control group), and 85 were admitted after May 2009 (intervention group). There were no significant differences between the two groups regarding baseline characteristics, such as injury severity and mortality. Additionally, there was no difference between the two groups in the mean number of total CT examinations per patient (4.8 vs. 4.5, respectively; p = 0.227). However, the mean effective dose of the total CT examinations per patient significantly decreased from 78.71 mSv to 29.50 mSv (p < 0.001).

Conclusions

The radiation dose reduction strategy for CT in severely injured trauma patients effectively decreased the cumulative effective dose of the total CT examinations in the emergency department. But not effectively decreased the number of CT examinations.