bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysing the effect of area of residence over the life course in multilevel epidemiology
Authors: Næss Øyvind , Leyland Alastair H.
Published: November 2010

Background: In this paper we present multilevel models of individuals’ residential history at multiple time points through the life course and their application and discuss some advantages and disadvantages for their use in epidemiological studies. Methods: Literature review of research using longitudinal multilevel models in studies of neighbourhood effects, statistical multilevel models that take individuals’ residential history into account, and the application of these models in the Oslo mortality study. Results: Measures of variance have been used to investigate the contextual impact of membership to collectives, such as area of residence, at several time points. The few longitudinal multilevel models that have been used suggest that early life area of residence may have an effect on mortality independently of residence later in life although the proportion of variation attributable to area level is small compared to individual level. The following multilevel models have been developed: simple multilevel models for each year separately, a multiple membership model, a cross-classified model, and finally a correlated cross-classified model. These models have different assumptions regarding the timing of influence through the life course. Conclusions: To fully recognise the origin of adult chronic diseases, factors at all stages of the life course at both individual and area level needs to be considered in order to avoid biased estimates. Important challenges in making life course residential data available for research and assessing how changing administrative coding over time reflect contextual impact need to be overcome before these models can be implemented as normal practice in multilevel epidemiology.
Schoolyard physical activity in 14-year-old adolescents assessed by mobile GPS and heart rate monitoring analysed by GIS
Authors: Fjørtoft Ingunn , Löfman Owe , Halvorsen Thorén Kine
Published: November 2010

Background: Environmental settings seem to influence the activity patterns of children in neighbourhoods and schoolyards, the latter being an important arena to promote physical activity (PA) in school children. New technology has made it possible to describe free-living PA in interaction with the environment. Aims of study: This study focused on how schoolyard environments influenced the activity patterns and intensity levels in 14-year-old children and whether PA levels in adolescents complied with official recommendations. Another objective was to introduce methodology of using a mobile global positioning system (GPS) device with synchronous heart rate (HR) recordings as a proxy for PA level and a geographical information system (GIS) for spatial analyses. Methods: The sample constituted of 81 children (aged 14 years) from two schools. Movement patterns and activity levels were recorded during lunch break applying a GPS Garmin Forerunner 305 with combined HR monitoring and analysed in a GIS by an overlaid grid and kriging interpolation. Results: Spatial data from GPS recordings showed particular movement patterns in the schoolyards. Low activity levels (mean HR < 120 bpm) dominated in both schools with no gender differences. Activities located to a handball goal area showed the highest monitored HR (>160 bpm) with higher intensity in girls than in boys. Conclusions: Movement patterns and PA generated in GIS for visualisation and analysis enabled direct and realistic description of utilising of schoolyard facilities and activity levels. Linking GPS data and PA levels to spatial structures made it possible to visualise the environmental interaction with PA and which environments promoted low or high PA.
‘In our experience’: Chairing and commissioning Serious Case Reviews in adult safeguarding in England
Authors: Manthorpe Jill , Martineau Stephen
Published: November 2010

• Summary: The article reports findings from an audit of Serious Case Reviews into the death or harm of a vulnerable adult in England. Serious Case Reviews may be undertaken by local authorities in partnership with other agencies. There is little government guidance and practice appears variable.

• Findings: Interviews were undertaken in 2007 with persons who had been appointed to Chair Serious Case Reviews and with those who commissioned such Reviews or managed the process. The findings confirm the aspiration of such Reviews to be opportunities for learning from mistakes, if any, and to thereby offer greater safeguards for vulnerable adults. In practice however, the conduct of such Reviews may be difficult if there is a lack of cooperation, a lack of resources and if there is little opportunity to share findings and recommendations outside the locality.

• Application: This study supports the sharing of Serious Case Reviews to encourage learning from mistakes and missed opportunities to safeguard vulnerable adults. It also found agreement among those with experience in such Reviews that greater guidance on conduct and collaboration would be welcome.
‘Love them to bits; spend time with them; have fun with them’: New Zealand parents’ views of building attachments with their newly adopted Russian children
Authors: Johnstone Jocelyn , Gibbs Anita
Published: November 2010

• Summary: Focus groups and semi-structured interviews were conducted with 15 parents from New Zealand who had adopted Russian born children. The aim of the research was to explore the ways in which parents establish and build their parenting and attachment relationships with their ‘new’ children.

• Findings: Findings revealed the immense commitment, child-centred focus, and conscious parenting of parents. The range of strategies used to build relationships and attachments included: quality time, play, touch and holding, and communication. Parents’ high levels of commitment were established through preparation to adopt, especially the acquisition of knowledge about and understanding of attachment issues. Support groups, notably other adoptive parents were also critical to enhancing relationships between children and their adoptive parents. Fathers were actively engaged in the process of building attachments.

• Applications: Intercountry adoptive parenting is a special kind of parenting, especially because of the challenges presented by children often neglected or abused prior to adoption. Helping prepare parents for both the rewards and challenges of intercountry adoption and supporting them post-adoption still needs to be improved by professional social work services. Acknowledgement of parents’ and children’s resilience and strengths that they bring to the new relationship will help create realistic expectations on the part of professionals and would-be adopters.
Improvement in ACE I/D polymorphism detection
Authors: Bolli Paola , Sticchi Elena , Giusti Betti , Saracini Claudia , Abbate Rosanna , Fatini Cinzia
Published: November 2010

The ACE I/D polymorphism has been reported to influence predisposition to cardiovascular disease. Conflicting results in its detection may be due to mistyping of I/D genotypes as D/D genotypes occurring in the traditional genotyping method. In order to resolve mistyping troubles and to permit a rapid and accurate analysis, we performed a stepdown PCR reaction followed by detection using Nanogen technology, and we compared these results with those obtained from traditional genotyping methods, such as conventional and confirmatory PCR. The Nanogen stepdown method showed a 100% sensitivity and 99.6% specificity, when compared with the confirmatory PCR. Our experiments provide evidence that, by using the Nanogen stepdown method, the DD mistyping was markedly decreased, thus representing a useful tool suitable for performing large-scale screening or research.
Difference as Ethical Encounter
Authors: Gannon Susanne
Published: November 2010

This article uses Deleuze and Levinas and those who work with their ideas to explore pedagogical encounters across difference in two texts: A collective biography story of a White teacher in an Indigenous school and an excerpt from the landmark “Sorry” speech by the previous Australian Prime Minister Kevin Rudd. It begins with a reflection on the methodology of collective biography and speculates on how difference, and ethical encounters across difference, might be rethought in ways that demassify categories of difference and at the same time recognize the exigencies of historical disadvantage.
Glabridin Inhibits Migration, Invasion, and Angiogenesis of Human Non–Small Cell Lung Cancer A549 Cells by Inhibiting the FAK/Rho Signaling Pathway
Authors: Tsai Ying-Ming , Yang Chih-Jen , Hsu Ya-Ling , Wu Ling-Yu , Tsai Yu-Chieh , Hung Jen-Yu , Lien Chi-Tun , Huang Ming-Shyan , Kuo Po-Lin
Published: November 2010

This study reports the antimigration, anti-invasive effect of glabridin, a flavonoid obtained from licorice, in human non–small cell lung cancer A549 cells. Glabridin exhibited effective inhibition of cell metastasis by decreasing cancer cell migration and invasion of A549 cells. In addition, glabridin also decreased A549-mediated angiogenesis. Further investigation revealed that glabridin’s inhibition of cancer angiogenesis was also evident in a nude mice model. Blockade of A549 cells migration was associated with an increase of ανβ3 integrin proteosome degradation. Glabridin also decreased the active forms of FAK and Src, and enhanced levels of inactivated phosphorylated Src (Tyr 527), decreasing the interaction of FAK and Src. Inhibition of the FAK/Src complex by glabridin also blocked Akt activation, resulting in reduced activation of RhoA and myosin light chain phosphorylation. This study demonstrates that glabridin may be a novel anticancer agent for the treatment of lung cancer in 3 different ways: inhibition of migration, invasion, and angiogenesis.
Vernonia cinerea Less. Inhibits Tumor Cell Invasion and Pulmonary Metastasis in C57BL/6 Mice
Authors: Pratheeshkumar Poyil , Kuttan Girija
Published: November 2010

The effect of Vernonia cinerea Less. extract on the inhibition of lung metastasis induced by B16F-10 melanoma cells was studied in C57BL/6 mice. V cinerea extract significantly ( P < .001) inhibited lung tumor formation (78.8%) and significantly increased the life span (72.5%). Moreover, lung collagen hydroxyproline, uronic acid, and hexosamine and also serum sialic acid, γ-glutamyltransferase (GGT), and vascular endothelial growth factor (VEGF) levels were found to be significantly ( P < .001) lower in treated animals compared with untreated controls. Histopathological analysis of the lung tissues also correlated with these findings. V cinerea treatment significantly inhibited the invasion of B16F-10 melanoma cells across the collagen matrix of the Boyden chamber. V cinerea also inhibited the migration of B16F-10 melanoma cells across a polycarbonate filter in vitro. It downregulated the production and expression of proinflammatory cytokines such as TNF (tumor necrosis factor)-α, IL (interleukin)-1β, IL-6, and GM-CSF (granulocyte monocyte colony-stimulating factor). V cinerea extract administration could suppress or downregulate the expression of matrix metalloproteinase (MMP)-2, MMP-9, lysyl oxidase, prolyl hydroxylase, K-ras, extracellular signal-regulated kinase (ERK)-1, ERK-2, and VEGF and also upregulate the expression of nm-23, tissue inhibitor of metalloproteinase (TIMP-1), and TIMP-2 in the lung tissue of metastasis-induced animals. It also inhibited the protein expression of MMP-2 and MMP-9 in gelatin zymographic analysis of B16F-10 cells. These results indicate that V cinerea could inhibit the metastatic progression of B16F-10 melanoma cells in C57BL/6 mice by regulating MMPs, VEGF, prolyl hydroxylase, lysyl oxidase, ERK-1, ERK-2, TIMPs, nm23, and proinflammatory cytokine gene expression in metastatic lung tissue.
Single-Access Transumbilical Laparoscopic Nissen Fundoplication Performed With New Curved Reusable Instruments
Authors: Dapri Giovanni , Bruyns Jean , Himpens Jacques , Cadière Guy Bernard
Published: November 2010

Introduction: The authors report a single-access laparoscopic Nissen fundoplication (SALN) performed with new curved reusable instruments. Case report: A 21-year-old woman sought care for symptomatic grade B esophagitis and hiatal hernia. A reusable 11-mm trocar was inserted in the umbilicus and a 10-mm, 30° angled, nonflexible, standard length scope was used. Curved reusable instruments (Karl Storz-Endoskope) were transumbilically introduced without trocars. The left hepatic lobe was retracted thanks to the distal curve of the grasper. The cruraplasty and wrap were performed using curved needle holder and intracorporeal sutures. Results: No extraumbilical trocar was necessary. Laparoscopic time was 108 minutes, and umbilical scar length was 16 mm. Discharge was allowed after 48 hours. Conclusions: SALN is feasible to be performed with curved reusable instruments, which avoid the conflict between the instruments’ tips inside the abdomen or between the surgeon’s hands outside. Cost of the procedure remains similar to standard laparoscopy because only reusable material is used.
A study to define: profound and multiple learning disabilities (PMLD)
Authors: Bellamy Gary , Croot Liz , Bush Alick , Berry Hilary , Smith Antoin
Published: November 2010

This study aimed to define the term ‘profound and multiple learning disabilities’ (PMLD). A shared understanding of terminology or diagnostic terms describing groups of individuals is important for the purposes of strategic development, service planning, and the provision and equity of service delivery. A literature review provided different definitions and meanings associated with the term. The meaning attributed to the definitions was explored in focus groups and individual interviews (face to face and telephone) with service managers, commissioners, practitioners, frontline healthcare staff and family carers who provide services, support and care for people with PMLD. Further iterative discussions were held with a smaller group over the precise wording of the chosen definition to ensure there was a shared and common understanding. Personal characteristics for the purpose of this study are defined as diagnoses, disabilities, impairments, activity restrictions and other characteristics which represent a person with PMLD.
PD-L1 blockade effectively restores strong graft-versus-leukemia effects without graft-versus-host disease after delayed adoptive transfer of T-cell receptor gene-engineered allogeneic CD8+ T cells
Authors: Koestner Wolfgang , Hapke Martin , Herbst Jessica , Klein Christoph , Welte Karl , Fruehauf Joerg , Flatley Andrew , Vignali Dario A. , Hardtke-Wolenski Matthias , Jaeckel Elmar , Blazar Bruce R. , Sauer Martin G.
Published: November 2010

Adoptive transfer (AT) of T cells forced to express tumor-reactive T-cell receptor (TCR) genes is an attractive strategy to direct autologous T-cell immunity against tumor-associated antigens. However, clinical effectiveness has been hampered by limited in vivo persistence. We investigated whether the use of major histocompatibility complex–mismatched T cells would prolong the in vivo persistence of tumor-reactive TCR gene expressing T cells by continuous antigen-driven proliferation via the endogenous potentially alloreactive receptor. Donor-derived CD8+ T cells engineered to express a TCR against a leukemia-associated antigen mediated strong graft-versus-leukemia (GVL) effects with reduced graft-versus-host disease (GVHD) severity when given early after transplantation. AT later after transplantation resulted in a complete loss of GVL. Loss of function was associated with reduced expansion of TCR-transduced T cells as assessed by CDR3 spectratyping analysis and PD-1 up-regulation on T cells in leukemia-bearing recipients. PD-L1 blockade in allogeneic transplant recipients largely restored the GVL efficacy without triggering GVHD, whereas no significant antileukemia effects of PD-L1 blockade were observed in syngeneic controls. These data suggest a clinical approach in which the AT of gene-modified allogeneic T cells early after transplantation can provide a potent GVL effect without GVHD, whereas later AT is effective only with concurrent PD-L1 blockade.
Granulocyte colony-stimulating factor attenuates oxidative stress–induced apoptosis in vascular endothelial cells and exhibits functional and morphologic protective effect in oxygen-induced retinopathy
Authors: Kojima Hiroshi , Otani Atsushi , Oishi Akio , Makiyama Yukiko , Nakagawa Satoko , Yoshimura Nagahisa
Published: November 2010

Granulocyte colony-stimulating factor (G-CSF) is a known hematopoietic glycoprotein, and recent studies have revealed that G-CSF possesses other interesting properties. Oxidative stress is involved in many diseases, such as atherosclerosis, heart failure, myocardial infarction, Alzheimer disease, and diabetic retinopathy. This study was designed to examine whether G-CSF has a protective effect on endothelial cells against oxidative stress and to investigate whether G-CSF has a therapeutic role in ischemic vascular diseases. Expression of G-CSF (P < .01) and G-CSF receptor (P < .05) mRNA in human retinal endothelial cells (HRECs) was significantly up-regulated by oxidative stress. Treatment with 100 ng/mL G-CSF significantly reduced H2O2-induced apoptosis in HRECs from 61.7% to 41.4% (P < .05). Akt was phosphorylated in HRECs by G-CSF addition, and LY294002, a PI3K inhibitor, significantly attenuated the antiapoptotic effect of G-CSF (by 44.1%, P < .05). The rescue effect was also observed in human umbilical vein endothelial cells. In mouse oxygen-induced retinopathy model, G-CSF significantly reduced vascular obliteration (P < .01) and neovascular tuft formation (P < .01). G-CSF treatment also clearly rescued the functional and morphologic deterioration of the neural retina. A possibility of a novel therapeutic strategy for ischemic diseases through attenuating vascular regression using G-CSF was proposed.
Enhanced erythropoiesis in Hfe-KO mice indicates a role for Hfe in the modulation of erythroid iron homeostasis
Authors: Ramos Pedro , Guy Ella , Chen Nan , Proenca Catia C. , Gardenghi Sara , Casu Carla , Follenzi Antonia , Van Rooijen Nico , Grady Robert W. , de Sousa Maria , Rivella Stefano
Published: November 2010

In hereditary hemochromatosis, mutations in HFE lead to iron overload through abnormally low levels of hepcidin. In addition, HFE potentially modulates cellular iron uptake by interacting with transferrin receptor, a crucial protein during erythropoiesis. However, the role of HFE in this process was never explored. We hypothesize that HFE modulates erythropoiesis by affecting dietary iron absorption and erythroid iron intake. To investigate this, we used Hfe-KO mice in conditions of altered dietary iron and erythropoiesis. We show that Hfe-KO mice can overcome phlebotomy-induced anemia more rapidly than wild-type mice (even when iron loaded). Second, we evaluated mice combining the hemochromatosis and β-thalassemia phenotypes. Our results suggest that lack of Hfe is advantageous in conditions of increased erythropoietic activity because of augmented iron mobilization driven by deficient hepcidin response. Lastly, we demonstrate that Hfe is expressed in erythroid cells and impairs iron uptake, whereas its absence exclusively from the hematopoietic compartment is sufficient to accelerate recovery from phlebotomy. In summary, we demonstrate that Hfe influences erythropoiesis by 2 distinct mechanisms: limiting hepcidin expression under conditions of simultaneous iron overload and stress erythropoiesis, and impairing transferrin-bound iron uptake by erythroid cells. Moreover, our results provide novel suggestions to improve the treatment of hemochromatosis.
Regulation of sonic hedgehog-GLI1 downstream target genes PTCH1, Cyclin D2, Plakoglobin, PAX6 and NKX2.2 and their epigenetic status in medulloblastoma and astrocytoma
Authors: Shahi Mehdi H , Afzal Mohammad , Sinha Subrata , Eberhart Charles G , Rey Juan A , Fan Xing , Castresana Javier S
Published: November 2010

Background

The Sonic hedgehog (Shh) signaling pathway is critical for cell growth and differentiation. Impairment of this pathway can result in both birth defects and cancer. Despite its importance in cancer development, the Shh pathway has not been thoroughly investigated in tumorigenesis of brain tumors. In this study, we sought to understand the regulatory roles of GLI1, the immediate downstream activator of the Shh signaling pathway on its downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6 in medulloblastoma and astrocytic tumors.

Methods

We silenced GLI1 expression in medulloblastoma and astrocytic cell lines by transfection of siRNA against GLI1. Subsequently, we performed RT-PCR and quantitative real time RT-PCR (qRT-PCR) to assay the expression of downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6. We also attempted to correlate the pattern of expression of GLI1 and its regulated genes in 14 cell lines and 41 primary medulloblastoma and astrocytoma tumor samples. We also assessed the methylation status of the Cyclin D2 and PTCH1 promoters in these 14 cell lines and 58 primary tumor samples.

Results

Silencing expression of GLI1 resulted up-regulation of all target genes in the medulloblastoma cell line, while only PTCH1 was up-regulated in astrocytoma. We also observed methylation of the cyclin D2 promoter in a significant number of astrocytoma cell lines (63%) and primary astrocytoma tumor samples (32%), but not at all in any medulloblastoma samples. PTCH1 promoter methylation was less frequently observed than Cyclin D2 promoter methylation in astrocytomas, and not at all in medulloblastomas.

Conclusions

Our results demonstrate different regulatory mechanisms of Shh-GLI1 signaling. These differences vary according to the downstream target gene affected, the origin of the tissue, as well as epigenetic regulation of some of these genes.
Improved vanillin production in baker's yeast through in silico design
Authors: Brochado Ana Rita , Matos Claudia , Møller Birger L , Hansen Jørgen , Mortensen Uffe H , Patil Kiran Raosaheb
Published: November 2010

Background

Vanillin is one of the most widely used flavouring agents, originally obtained from cured seed pods of the vanilla orchid Vanilla planifolia. Currently vanillin is mostly produced via chemical synthesis. A de novo synthetic pathway for heterologous vanillin production from glucose has recently been implemented in baker's yeast, Saccharamyces cerevisiae. In this study we aimed at engineering this vanillin cell factory towards improved productivity and thereby at developing an attractive alternative to chemical synthesis.

Results

Expression of a glycosyltransferase from Arabidopsis thaliana in the vanillin producing S. cerevisiae strain served to decrease product toxicity. An in silico metabolic engineering strategy of this vanillin glucoside producing strain was designed using a set of stoichiometric modelling tools applied to the yeast genome-scale metabolic network. Two targets (PDC1 and GDH1) were selected for experimental verification resulting in four engineered strains. Three of the mutants showed up to 1.5 fold higher vanillin β-D-glucoside yield in batch mode, while continuous culture of the Δpdc1 mutant showed a 2-fold productivity improvement. This mutant presented a 5-fold improvement in free vanillin production compared to the previous work on de novo vanillin biosynthesis in baker's yeast.

Conclusion

Use of constraints corresponding to different physiological states was found to greatly influence the target predictions given minimization of metabolic adjustment (MOMA) as biological objective function. In vivo verification of the targets, selected based on their predicted metabolic adjustment, successfully led to overproducing strains. Overall, we propose and demonstrate a framework for in silico design and target selection for improving microbial cell factories.
Modulation of extracellular matrix/adhesion molecule expression by BRG1 is associated with increased melanoma invasiveness
Authors: Saladi Srinivas Vinod , Keenen Bridget , Marathe Himangi G , Qi Huiling , Chin Khew-Voon , de la Serna Ivana L
Published: November 2010

Background

Metastatic melanoma is an aggressive malignancy that is resistant to therapy and has a poor prognosis. The progression of primary melanoma to metastatic disease is a multi-step process that requires dynamic regulation of gene expression through currently uncharacterized epigenetic mechanisms. Epigenetic regulation of gene expression often involves changes in chromatin structure that are catalyzed by chromatin remodeling enzymes. Understanding the mechanisms involved in the regulation of gene expression during metastasis is important for developing an effective strategy to treat metastatic melanoma. SWI/SNF enzymes are multisubunit complexes that contain either BRG1 or BRM as the catalytic subunit. We previously demonstrated that heterogeneous SWI/SNF complexes containing either BRG1 or BRM are epigenetic modulators that regulate important aspects of the melanoma phenotype and are required for melanoma tumorigenicity in vitro.

Results

To characterize BRG1 expression during melanoma progression, we assayed expression of BRG1 in patient derived normal skin and in melanoma specimen. BRG1 mRNA levels were significantly higher in stage IV melanomas compared to stage III tumors and to normal skin. To determine the role of BRG1 in regulating the expression of genes involved in melanoma metastasis, we expressed BRG1 in a melanoma cell line that lacks BRG1 expression and examined changes in extracellular matrix and adhesion molecule expression. We found that BRG1 modulated the expression of a subset of extracellular matrix remodeling enzymes and adhesion proteins. Furthermore, BRG1 altered melanoma adhesion to different extracellular matrix components. Expression of BRG1 in melanoma cells that lack BRG1 increased invasive ability while down-regulation of BRG1 inhibited invasive ability in vitro. Activation of metalloproteinase (MMP) 2 expression greatly contributed to the BRG1 induced increase in melanoma invasiveness. We found that BRG1 is recruited to the MMP2 promoter and directly activates expression of this metastasis associated gene.

Conclusions

We provide evidence that BRG1 expression increases during melanoma progression. Our study has identified BRG1 target genes that play an important role in melanoma metastasis and we show that BRG1 promotes melanoma invasive ability in vitro. These results suggest that increased BRG1 levels promote the epigenetic changes in gene expression required for melanoma metastasis to proceed.
The correlation between urinary 5-hydroxyindoleacetic acid and sperm quality in infertile men and rotating shift workers
Authors: Ortiz Águeda , Espino Javier , Bejarano Ignacio , Lozano Graciela M , Monllor Fabián , García Juan F , Pariente José A , Rodríguez Ana B
Published: November 2010

Background

Serotonin is a neurotransmitter that modulates a wide range of neuroendocrine functions. However, excessive circulating serotonin levels may induce harmful effects in the male reproductive system. The objective of this study was to evaluate whether the levels of urinary 5-hydroxyindoleacetic acid (5-HIIA), a major serotonin metabolite, correlate with different classical seminal parameters.

Methods

Human ejaculates were obtained from 40 men attending infertility counselling and rotating shift workers by masturbation after 4-5 days of abstinence. Urinary 5- HIIA concentration was quantified by using a commercial ELISA kit. Forward motility was assessed by a computer-aided semen analysis (CASA) system. Sperm concentration was determined using the haemocytometer method. Sperm morphology was evaluated after Diff-Quik staining, while sperm vitality was estimated after Eosin-Nigrosin vital staining.

Results

Our results show that urinary 5-HIIA levels obtained from a set of 20 volunteers negatively correlated with sperm concentration, forward motility, morphology normal range and sperm vitality. On the other hand, we checked the relationship between male infertility and urinary 5-HIIA levels in 20 night shift workers. Thus, urinary 5-HIIA levels obtained from 10 recently-proven fathers were significantly lower than those found in 10 infertile males. Additionally, samples from recent fathers exhibited higher sperm concentration, as well as better forward motility and normal morphology rate.

Conclusions

In the light of our findings, we concluded that high serotonin levels, indirectly measured as urinary 5-HIIA levels, appear to play a role as an infertility determinant in male subjects.
Multi-level reproducibility of signature hubs in human interactome for breast cancer metastasis
Authors: Yao Chen , Li Hongdong , Zhou Chenggui , Zhang Lin , Zou Jinfeng , Guo Zheng
Published: November 2010

Background

It has been suggested that, in the human protein-protein interaction network, changes of co-expression between highly connected proteins ("hub") and their interaction neighbours might have important roles in cancer metastasis and be predictive disease signatures for patient outcome. However, for a cancer, such disease signatures identified from different studies have little overlap.

Results

Here, we propose a systemic approach to evaluate the reproducibility of disease signatures at multiple levels, on the basis of some statistically testable biological models. Using two datasets for breast cancer metastasis, we showed that different signature hubs identified from different studies were highly consistent in terms of significantly sharing interaction neighbours and displaying consistent co-expression changes with their overlapping neighbours, whereas the shared interaction neighbours were significantly over-represented with known cancer genes and enriched in pathways deregulated in breast cancer pathogenesis. Then, we showed that the signature hubs identified from the two datasets were highly reproducible at the protein interaction and pathway levels in three other independent datasets.

Conclusions

Our results provide a possible biological model that different signature hubs altered in different patient cohorts could disturb the same pathways associated with cancer metastasis through their interaction neighbours.
Sex- and brain region-specific acceleration of β-amyloidogenesis following behavioral stress in a mouse model of Alzheimer's disease
Authors: Devi Latha , Alldred Melissa J , Ginsberg Stephen D , Ohno Masuo
Published: November 2010

Background

It is hypothesized that complex interactions between multiple environmental factors and genetic factors are implicated in sporadic Alzheimer's disease (AD); however, the underlying mechanisms are poorly understood. Importantly, recent evidence reveals that expression and activity levels of the β-site APP cleaving enzyme 1 (BACE1), which initiates amyloid-β (Aβ) production, are elevated in AD brains. In this study, we investigated a molecular mechanism by which sex and stress interactions may accelerate β-amyloidogenesis and contribute to sporadic AD.

Results

We applied 5-day restraint stress (6 h/day) to the male and female 5XFAD transgenic mouse model of AD at the pre-pathological stage of disease, which showed little amyloid deposition under non-stressed control conditions. Exposure to the relatively brief behavioral stress increased levels of neurotoxic Aβ42 peptides, the β-secretase-cleaved C-terminal fragment (C99) and plaque burden in the hippocampus of female 5XFAD mice but not in that of male 5XFAD mice. In contrast, significant changes in the parameters of β-amyloidosis were not observed in the cerebral cortex of stressed male or female 5XFAD mice. We found that this sex- and brain region-specific acceleration of β-amyloidosis was accounted for by elevations in BACE1 and APP levels in response to adverse stress. Furthermore, not only BACE1 mRNA but also phosphorylation of the translation initiation factor eIF2α (a proposed mediator of the post-transcriptional upregulation of BACE1) was elevated in the hippocampus of stressed female 5XFAD mice.

Conclusions

Our results suggest that the higher prevalence of sporadic AD in women may be attributable to the vulnerability of female brains (especially, the hippocampus) to stressful events, which alter APP processing to favor the β-amyloidogenesis through the transcriptional and translational upregulation of BACE1 combined with elevations in its substrate APP.
Involvement of mitochondrial pathway in NCTD-induced cytotoxicity in human hepG2 cells
Authors: Chang Cheng , Zhu You-Qing , Mei Juan-juan , Liu Shi-quan , Luo Jun
Published: November 2010

Background

Norcantharidin, the demethylated analog of cantharidin derived from a traditional Chinese medicine, Mylabris, has been used in the treatment of anti-cancer effects. However, the detailed mechanisms underlying this process are generally unclear. The aim of this study was to investigate the mechanism of NCTD-induced apoptosis in HepG2 cells.

Methods

The cytotoxicity was measured by MTT assay for cellular viability and by flow cytometry. The mitochondrial membrane potential and reactive oxygen species production was evaluated by flow cytometry analysis. The role of caspase activities were assayed using caspase apoptosis detection kit . Western blot analysis was used to evaluate the level of Cyto-C, Bcl-2, Bax, Bid, caspase 3, -9, -8 and PARP expression

Results

After treatment with NCTD, a decrease in the viability of HepG2 cells and increase in apoptosis were observed. NCTD-induced apoptosis was accompanied by an increase in ROS production, loss of mitochondrial membrane potential and release of cytochrome c(cyto-c) from the mitochondria to the cytosol and down-regulation of anti-apoptotic protein Bcl-2 levels with concurrent up-regulation in pro-apoptotic protein Bax levels. However, another pro-apoptotic molecule, Bid, showed no change in such same treatment. NCTD-increased activity of caspase 9,caspase 3 and the subsequent cleavage caspase substrate PARP were also observed. The expression levels of pro-caspase-8 were not changed after NCTD treatment.

Conclusion

These results indicate that NCTD induced cytotoxicity in HepG2 cells by apoptosis, which is mediated through ROS generation and mitochondrial pathway.
The changing face of HIV resistance; HIV drug resistance north and south — what's next?
Authors: Schapiro J
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Impact of baseline HIV‐1 tropism on viral response and CD4 gains in antiretroviral‐naïve patients
Authors: Seclén E , Gonzalez M , Martín‐Carbonero L , Gellermann H , Cairns V , Distel M , Kadus W , Soriano V , Poveda E
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Low‐level viraemia during treatment with darunavir/r monotherapy versus DRV/r + 2NRTIs in the MONET trial
Authors: Clumeck N , Arribas JR , Pulick P , Fätkenheuer G , Hill A , Van Delft Y , Moecklinghoff C
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Major issues and their solutions in the management of HIV and TB — from the laboratory to the patient and population
Authors: Schechter M
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Short‐term variation of HIV tropism readouts in the absence of CCR5 antagonists
Authors: Brumme CJ , Dong W , Chan D , Mo T , Swenson LC , Woods C , Demarest J , Heera J , Valdez H , Harrigan PR
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Safety and efficacy of maraviroc (MVC) combined with multiple different therapeutic agents in highly treatment‐experienced (TE) patients in Brazil
Authors: Furtado JJD , Madruga JV , Bicudo EL , Eira M , Lopes MIB , Netto EM , de Oliveira MS , Leite OHM , Machado AA , Tupinambas U , de Andrade Neto JL , Lima MPJ , Wajsbrot DB , Cassoli LM
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Resistance after viral failure on atazanavir‐containing therapy: multinational clinical cohort (BMS AI424‐128 — ‘IMPACT’) final analysis
Authors: Zolopa A , Towner W , Lazzarin A , Fätkenheuer G , Butcher D , Uy J
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Feasibility and effectiveness of combination antiretroviral therapy in HIV‐infected infants in Pietermaritzburg, South Africa
Authors: Van der Linden D , Purchase S , McKerrow NH
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Minority M184V variants in women exposed to 3TC/FTC‐containing lopinavir‐ritonavir (LPVr) regimens in pregnancy
Authors: Surah S , Oshea S , Costelloe S , Hanlon M , Mullen J , Chrystie I , Taylor GP , De Ruiter A
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Older HIV‐infected individuals present late and have a higher mortality: a UK clinic cohort study
Authors: Iwuji CC , Pao D , Gilleece Y , Fisher M , Churchill D
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
T‐CD4+ cell count at the date of the HIV diagnosis
Authors: Domingues da Silva AR , Mendez J , e Castro R Sarmento
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Pharmacokinetics of plasma lopinavir/ritonavir following the administration of 400/100, 200/150, and 200/50 mg twice daily in HIV‐negative volunteers
Authors: Jackson AGA , Hill A , Else LJ , Back DJ , Morley R , Puls R , Amin J , Lin E , Boffito M
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Population pharmacokinetic and pharmacogenetic analysis of nevirapine in hypersensitive and tolerant HIV‐infected patients from Malawi
Authors: Dickinson L , Chaponda M , Carr D , van Oosterhout JJ , Kumwenda J , Lalloo DG , Pirmohamed M , Heyderman R , Khoo SH
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Effect of intrinsic and extrinsic factors on the pharmacokinetics of TMC278 in antiretroviral‐naïve, HIV‐1‐infected patients in ECHO and THRIVE
Authors: Crauwels HM , van Schaick E , van Heeswijk RPG , Vanveggel S , Boven K , Vis P
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
The management of acute retroviral syndrome
Authors: Hristea A , Petre R , Gliga S , Olaru I , Ion M , Moroti R , Popescu C , Mihailescu R , Radulescu M , Arama V
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Cost‐effectiveness of 2NRTI+NNRTI versus 2NRTI+PI as the initial cART regimen
Authors: Aragão F , Vaz Pinto I , Vera J
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Influence of demographic and disease parameters on virological response to once‐ vs twice‐daily darunavir/ritonavir (DRV/r) at week 48 in ODIN
Authors: Sension M , Arns Da Cunha C , Domingo P , Supparatpinyo K , Van De Casteele T , De Doncker P , Tomaka F
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Efficacy and tolerability of darunavir/r 600/100 mg bid in treatment‐experienced patients: 48‐week data from a German outpatient cohort
Authors: van Lunzen J , Gorriahn D , Wünsche T , Dupke S , Gute P , Schewe CK , Ranneberg B
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Efficacy and safety of lopinavir/ritonavir (LPV/r) in antiretroviral‐experienced subjects infected with different subtypes of HIV‐1
Authors: Maroldo L , Fredrick LM , Robinson‐Morgan K , Trinh R , Podsadecki TJ
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Nevirapine (NVP) vs ritonavir‐boosted atazanavir (ATV/r) combined with tenofovir/emtricitabine (TDF/FTC) in first‐line therapy: NEWART 48‐week data
Authors: DeJesus E , Mills A , Bhatti L , Conner C , Storfer S
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Short‐course intensification with enfuvirtide in virologic failure: impact on intracellular HIV reservoir and on viral tropism (INNOVE study)
Authors: Ghosn J , Delaugerre C , Pinta A , Pierre N , Etienne D , Raffi F , Morand‐Joubert L
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Efficacy of once daily darunavir/ritonavir 800/100 mg in PI/r‐experienced HIV‐1 infected patients with suppressed HIV‐1 replication: the RADAR study
Authors: Ghosn J , Chermak A , Houssaini A , Peytavin G , Lambert‐Niclot S , Eychenne N , Slama L , Brunet A , Duvivier C , Simon A , Marcelin AG , Flandre P , Katlama C
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Prediction of virological failure in HIV‐infected individuals treated with cART in Suriname
Authors: Bleijenberg MP , Bierman WFW , Jaglall C , Heymans MW , ten Doesschate MC , Nieuwkerk PT , Smits PH , van Eer M , Vreden S
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Incidence of ischemic cardiovascular events in the maraviroc clinical development program
Authors: Portsmouth S , Burnside R , Lazzarin A , Johnson M , Valdez H
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Dietician‐based approach to lipodystrophic syndrome: role of bioelectrical impedance analysis at week 12
Authors: Orofino G , Guastavigna M , Martinoglio P , Penoncelli D , Demarie D , Tettoni M , Desiderato P , Di Frenna R , Zignin C
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Altered phosphate metabolism in HIV‐1‐infected patients: another feature of metabolic syndrome?
Authors: Grima P , Zizza A , Guido M , Calabrese P , Chiavaroli R , Sodo MR , Tana M , Tundo P
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
CD4 response, lipid changes and liver outcome in 506 patients receiving nevirapine‐based regimens for a median of 9 years
Authors: Podzamczer D , Tiraboschi JM , Mallolas J , Cárdenes MA , Casas E , Castro A , Echevarria S , Leal M , Bernanldo de Quirós JC Lopez , Moreno S , Puig T , Ribera E , Villalonga C , Gomez Sirvent JL , Garcia Heranejos JA , Lopez‐Aldeguer J , Barrufet P , Force L , Santos I , Sanz J
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Serologic Antienzyme Rate of Epstein-Barr Virus DNase-Specific Neutralizing Antibody Segregates TNM Classification in Nasopharyngeal Carcinoma
Authors: Xu Jie , Wan Xiang-Bo , Huang Xue-Fei , Chan K.C. Allen , Hong Ming-Huang , Wang Li-Hui , Long Zi-Jie , Liu Qing , Yan Min , Lo Y.M. Dennis , Zeng Yi-Xin , Liu Quentin
Published: November 2010

Purpose

We investigate the value of pretreatment serologic antienzyme rate (AER) of Epstein-Barr virus (EBV) DNase-specific neutralizing antibody complementing TNM staging in prognostication of nasopharyngeal carcinoma (NPC).

Patients and Methods

Pretreatment serum samples from 1,303 patients with untreated NPC were collected and examined for AER. After a 10-year follow-up period, the prognoses of the patients, classified by their clinical stage with AER, were assessed by multivariate analysis. Of the 1,303 patients, 600 patients were randomly assigned to a training set to generate an AER cutoff point by receiver operating characteristic (ROC) curve analysis. AER levels were then analyzed with overall survival (OS), progression-free survival (PFS), local failure–free survival (LFFS), and distant metastasis–free survival (DMFS) in a testing set (703 patients). Another independent cohort of 464 patients was studied in a validating set.

Results

In the training set, the ROC analysis–generated AER cutoff point for OS was 58.0%, which was used as the cutoff point in the testing set. The subset of low AER levels predicted a significant survival advantage over the subset of high AER levels for OS, PFS, LFFS, and DMFS in the testing set. Moreover, two distinguished subgroups were segregated by an AER level of 58.0% within each clinical stage comparing prognostication of OS, PFS, LFFS, and DMFS. Importantly, AER level was revealed as the only significant independent prognostic factor for death, recurrence, and distant metastasis in the validating set.

Conclusion

Pretreatment serologic AER of EBV DNase-specific neutralizing antibody serves as an independent prognostic marker complementing TNM stage in NPC. Supplementing pretreatment AER with TNM staging leads to more accurate risk definition in patient subgroups.
Neoadjuvant Chemotherapy Compared With Surgery Alone for Locally Advanced Cancer of the Stomach and Cardia: European Organisation for Research and Treatment of Cancer Randomized Trial 40954
Authors: Schuhmacher Christoph , Gretschel Stephan , Lordick Florian , Reichardt Peter , Hohenberger Werner , Eisenberger Claus F. , Haag Cornelie , Mauer Murielle E. , Hasan Baktiar , Welch John , Ott Katja , Hoelscher Arnulf , Schneider Paul M. , Bechstein Wolf , Wilke Hans , Lutz Manfred P. , Nordlinger Bernard , Cutsem Eric Van , Siewert Jörg R. , Schlag Peter M.
Published: November 2010

Purpose

Patients with locally advanced gastric cancer benefit from combined pre- and postoperative chemotherapy, although fewer than 50% could receive postoperative chemotherapy. We examined the value of purely preoperative chemotherapy in a phase III trial with strict preoperative staging and surgical resection guidelines.

Patients and Methods

Patients with locally advanced adenocarcinoma of the stomach or esophagogastric junction (AEG II and III) were randomly assigned to preoperative chemotherapy followed by surgery or to surgery alone. To detect with 80% power an improvement in median survival from 17 months with surgery alone to 24 months with neoadjuvant, 282 events were required.

Results

This trial was stopped for poor accrual after 144 patients were randomly assigned (72:72); 52.8% patients had tumors located in the proximal third of the stomach, including AEG type II and III. The International Union Against Cancer R0 resection rate was 81.9% after neoadjuvant chemotherapy as compared with 66.7% with surgery alone (P = .036). The surgery-only group had more lymph node metastases than the neoadjuvant group (76.5% v 61.4%; P = .018). Postoperative complications were more frequent in the neoadjuvant arm (27.1% v 16.2%; P = .09). After a median follow-up of 4.4 years and 67 deaths, a survival benefit could not be shown (hazard ratio, 0.84; 95% CI, 0.52 to 1.35; P = .466).

Conclusion

This trial showed a significantly increased R0 resection rate but failed to demonstrate a survival benefit. Possible explanations are low statistical power, a high rate of proximal gastric cancer including AEG and/or a better outcome than expected after radical surgery alone due to the high quality of surgery with resections of regional lymph nodes outside the perigastic area (celiac trunc, hepatic ligament, lymph node at a. lienalis; D2).