bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo distribution of β2 glycoprotein I under various pathophysiologic conditions
Authors: Agostinis Chiara , Biffi Stefania , Garrovo Chiara , Durigutto Paolo , Lorenzon Andrea , Bek Alpan , Bulla Roberta , Grossi Claudia , Borghi Maria O. , Meroni PierLuigi , Tedesco Francesco
Published: July 2011

In vitro studies have documented β2 glycoprotein I (β2GPI) binding to endothelial cells (ECs) and trophoblast using antiphospholipid antibodies. The in vivo binding of β2GPI to these cells and the conditions that favor their interaction have not been investigated. We analyzed the in vivo distribution of cyanine 5.5-labeled β2GPI in mice and evaluated the effect of pregnancy and circulating antibodies on its tissue localization. The signal was detected in the liver by whole body scan and ex vivo analysis. The β2GPI failed to bind to the vascular endothelium and reacted only with the ECs of uterine vessels. In pregnant mice the protein was localized on ECs and trophoblast at the embryo implantation sites. Immunized mice showed a similar β2GPI biodistribution to naive mice but the immunized pregnant animals exhibited a significant increase in fetal loss associated with C3 and C9 deposition at the implantation sites. Treatment of mice with LPS after β2GPI-Cy5.5 injection promoted protein localization on gut and brain ECs associated with IgG, C1q, and C9 deposition in immunized mice. These findings indicate that β2GPI binding to EC requires priming with pro-inflammatory factors which is not needed for uterine and placental localization probably dependent on hormonal changes.
Leukemic stem cell persistence in chronic myeloid leukemia patients with sustained undetectable molecular residual disease
Authors: Chomel Jean-Claude , Bonnet Marie-Laure , Sorel Nathalie , Bertrand Angelina , Meunier Marie-Claude , Fichelson Serge , Melkus Michael , Bennaceur-Griscelli Annelise , Guilhot François , Turhan Ali G.
Published: July 2011

Sustained undetectable molecular residual disease (UMRD) is obtained in a minority of patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors. It remains unclear whether these patients are definitively cured of their leukemia or whether leukemic stem cells (LSCs) persist in their BM. We have evaluated the presence of BCR-ABL–expressing marrow LSCs in 6 patients with chronic myeloid leukemia with sustained UMRD induced by IFN-α (n = 3), imatinib mesylate after IFN-α failure (n = 2), and dasatinib after imatinib intolerance (n = 1). Purified CD34+ cells were used for clonogenic and long-term culture-initiating cell assays performed on classic or HOXB4-expressing MS-5 feeders. Using this strategy, we identified BCR-ABL–expressing LSCs in all patients. Interestingly, long-term culture-initiating cell assays with MS-5/HOXB4 stromal feeders increased detected numbers of LSCs in 3 patients. The relation between LSC persistency and a potential risk of disease relapse for patients with durable UMRD (on or off tyrosine kinase inhibitor therapy) warrants further investigation.
Activation of p38 MAPK in CD4 T cells controls IL-17 production and autoimmune encephalomyelitis
Authors: Noubade Rajkumar , Krementsov Dimitry N. , del Rio Roxana , Thornton Tina , Nagaleekar Viswas , Saligrama Naresha , Spitzack Anthony , Spach Karen , Sabio Guadalupe , Davis Roger J. , Rincon Mercedes , Teuscher Cory
Published: July 2011

Although several transcription factors have been shown to be critical for the induction and maintenance of IL-17 expression by CD4 Th cells, less is known about the role of nontranscriptional mechanisms. Here we show that the p38 MAPK signaling pathway is essential for in vitro and in vivo IL-17 production by regulating IL-17 synthesis in CD4 T cells through the activation of the eukaryotic translation initiation factor 4E/MAPK-interacting kinase (eIF-4E/MNK) pathway. We also show that p38 MAPK activation is required for the development and progression of both chronic and relapsing-remitting forms of experimental allergic encephalomyelitis (EAE), the principal autoimmune model of multiple sclerosis. Furthermore, we show that regulation of p38 MAPK activity specifically in T cells is sufficient to modulate EAE severity. Thus, mechanisms other than the regulation of gene expression also contribute to Th17 cell effector functions and, potentially, to the pathogenesis of other Th17 cell–mediated diseases.
Is there a role for antigen selection in mantle cell lymphoma? Immunogenetic support from a series of 807 cases
Authors: Hadzidimitriou Anastasia , Agathangelidis Andreas , Darzentas Nikos , Murray Fiona , Delfau-Larue Marie-Helene , Pedersen Lone Bredo , Lopez Alba Navarro , Dagklis Antonis , Rombout Paul , Beldjord Kheira , Kolstad Arne , Dreyling Martin H. , Anagnostopoulos Achilles , Tsaftaris Athanasios , Mavragani-Tsipidou Penelope , Rosenwald Andreas , Ponzoni Maurilio , Groenen Patricia , Ghia Paolo , Sander Birgitta , Papadaki Theodora , Campo Elias , Geisler Christian , Rosenquist Richard , Davi Frederic , Pott Christiane , Stamatopoulos Kostas
Published: July 2011

We examined 807 productive IGHV-IGHD-IGHJ gene rearrangements from mantle cell lymphoma (MCL) cases, by far the largest series to date. The IGHV gene repertoire was remarkably biased, with IGHV3-21, IGHV4-34, IGHV1-8, and IGHV3-23 accounting for 46.3% of the cohort. Eighty-four of 807 (10.4%) cases, mainly using the IGHV3-21 and IGHV4-34 genes, were found to bear stereotyped heavy complementarity-determining region 3 (VH CDR3) sequences and were placed in 38 clusters. Notably, the MCL stereotypes were distinct from those reported for chronic lymphocytic leukemia. Based on somatic hypermutation (SHM) status, 238/807 sequences (29.5%) carried IGHV genes with 100% germ line identity; the remainder (569/807; 70.5%) exhibited different SHM impact, ranging from minimal (in most cases) to pronounced. Shared replacement mutations across the IGHV gene were identified for certain subgroups, especially those using IGHV3-21, IGHV1-8, and IGHV3-23. Comparison with other entities, in particular CLL, revealed that several of these mutations were “MCL-biased.” In conclusion, MCL is characterized by a highly restricted immunoglobulin gene repertoire with stereotyped VH CDR3s and very precise SHM targeting, strongly implying a role for antigen-driven selection of the clonogenic progenitors. Hence, an antigen-driven origin of MCL could be envisaged, at least for subsets of cases.
Gut inflammation and indoleamine deoxygenase inhibit IL-17 production and promote cytotoxic potential in NKp44+ mucosal NK cells during SIV infection
Authors: Reeves R. Keith , Rajakumar Premeela A. , Evans Tristan I. , Connole Michelle , Gillis Jacqueline , Wong Fay E. , Kuzmichev Yury V. , Carville Angela , Johnson R. Paul
Published: July 2011

Natural killer (NK) cells are classically viewed as effector cells that kill virus-infected and neoplastic cells, but recent studies have identified a rare mucosal NK- cell subpopulation secreting the TH17 cytokine IL-22. Here, we report identification of 2 distinct lineages of mucosal NK cells characterized as NKG2A+NFIL3+RORC– and NKp44+NFIL3+RORC+. NKG2A+ NK cells were systemically distributed, cytotoxic, and secreted IFN-γ, whereas NKp44+ NK cells were mucosae-restricted, noncytotoxic, and produced IL-22 and IL-17. During SIV infection, NKp44+ NK cells became apoptotic, were depleted, and had an altered functional profile characterized by decreased IL-17 secretion; increased IFN-γ secretion; and, surprisingly, increased potential for cytotoxicity. NKp44+ NK cells showed no evidence of direct SIV infection; rather, depletion and altered function were associated with SIV-induced up-regulation of inflammatory mediators in the gut, including indoleamine 2,3-dioxygenase 1. Furthermore, treatment of NKp44+ NK cells with indoleamine 2,3-dioxygenase 1 catabolites in vitro ablated IL-17 production in a dose-dependent manner, whereas other NK-cell functions were unaffected. Thus lentiviral infection both depletes and modifies the functional repertoire of mucosal NK cells involved in the maintenance of gut integrity, a finding that highlights the plasticity of this rare mucosal NK-cell population.
The miR-144/451eGFP allele, a novel tool for resolving the erythroid potential of hematopoietic precursors
Authors: Rasmussen Kasper D. , O'Carroll Dónal
Published: July 2011

A long outstanding problem is the resolution of the full potential of hematopoietic precursors. The commonly used allotypic marker Ly5 permits the tracing of lymphoid and granulocyte-macrophage (GM) output. Here we present a novel eGFP allele that allows the quantitative analysis of red blood cell (RBC) origin at the single-cell level. The miR-144/451 locus is required for erythroid development and homeostasis. Taking advantage of the fact that miR-451 is specifically and highly expressed in the erythroid lineage, we inserted an eGFP expression cassette into the miR-144/451 locus. In miR-144/451+/eGFP animals, accumulation of eGFP is exclusively observed during terminal erythroid differentiation. Expression of miR-144/451eGFP ignites immediately before the CFU-E stage and results in strong and complete labeling of all mature RBCs in circulation. Using competitive reconstitution experiments in the Ly5 transplant model, we show that eGFP linearly correlates with Ly5 expression. Thus, the miR-144/451eGFP allele represents a novel tool for the resolution of erythroid potential.
Approach to the treatment of multiple myeloma: a clash of philosophies
Authors: Rajkumar S. Vincent , Gahrton Gösta , Bergsagel P. Leif
Published: July 2011

In this Perspective, we summarize some of the most contentious issues surrounding diagnosis and treatment of myeloma. We outline how a fundamental clash of philosophies, cure versus control, may be at the heart of many of the controversies. From the very definition of the disease to risk stratification to the validity of current clinical trial endpoints, we highlight the major areas of debate and provide alternative viewpoints that have implications for trial design and interpretation, as well as clinical practice.
Bayesian semi-supervised classification of bacterial samples using MLST databases
Authors: Cheng Lu , Connor Thomas R , Aanensen David M , Spratt Brian G , Corander Jukka
Published: July 2011

Background

Worldwide effort on sampling and characterization of molecular variation within a large number of human and animal pathogens has lead to the emergence of multi-locus sequence typing (MLST) databases as an important tool for studying the epidemiology and evolution of pathogens. Many of these databases are currently harboring several thousands of multi-locus DNA sequence types (STs) enriched with metadata over traits such as serotype, antibiotic resistance, host organism etc of the isolates. Curators of the databases have thus the possibility of dividing the pathogen populations into subsets representing different evolutionary lineages, geographically associated groups, or other subpopulations, which are defined in terms of molecular similarities and dissimilarities residing within a database. When combined with the existing metadata, such subsets may provide invaluable information for assessing the position of a new set of isolates in relation to the whole pathogen population.

Results

To enable users of MLST schemes to query the databases with sets of new bacterial isolates and to automatically analyze their relation to existing curated sequences, we introduce here a Bayesian model-based method for semi-supervised classification of MLST data. Our method can use an MLST database as a training set and assign simultaneously any set of query sequences into the earlier discovered lineages/populations, while also allowing some or all of these sequences to form previously undiscovered genetically distinct groups. This tool provides probabilistic quantification of the classification uncertainty and is highly efficient computationally, thus enabling rapid analyses of large databases and sets of query sequences. The latter feature is a necessary prerequisite for an automated access through the MLST web interface. We demonstrate the versatility of our approach by anayzing both real and synthesized data from MLST databases. The introduced method for semi-supervised classification of sets of query STs is freely available for Windows, Mac OS X and Linux operative systems in BAPS 5.4 software which is downloadable athttp://web.abo.fi/fak/mnf/mate/jc/software/baps.html. The query functionality is also directly available for theStaphylococcus aureusdatabase athttp://www.mlst.netand shortly will be available for other species databases hosted at this web portal.

Conclusions

We have introduced a model-based tool for automated semi-supervised classification of new pathogen samples that can be integrated into the web interface of the MLST databases. In particular, when combined with the existing metadata, the semi-supervised labeling may provide invaluable information for assessing the position of a new set of query strains in relation to the particular pathogen population represented by the curated database.

Such information will be useful both for clinical and basic research purposes.
Inactivation and sub-lethal injury of salmonella typhi, salmonella typhimurium and vibrio cholerae in copper water storage vessels
Authors: Sharan Riti , Chhibber Sanjay , Reed Robert H
Published: July 2011

Background

This study provides information on the antibacterial effect of copper against the water-borne pathogens Salmonella Typhi, Salmonella Typhimurium and Vibrio cholerae.

Methods

Suspensions of each pathogen were kept in water within a traditional copper vessel at 30°C for 24 h. Samples were withdrawn, diluted and plated onto suitable growth media. Conventional enumeration of healthy (uninjured) bacteria was carried out using standard aerobic incubation conditions. Additionally, reactive oxygen species-neutralised (ROS-n) conditions were achieved by adding the peroxide scavenger sodium pyruvate to the medium with anaerobic incubation, to enumerate uninjured (ROS-insensitive) and injured (ROS-sensitive) bacteria. Differences between log-transformed means of conventional (aerobic) and ROS-n counts were statistically evaluated using t tests.

Results

Overall, all three pathogens were inactivated by storage in copper vessels for 24 h. However, for shorter-term incubation (4-12 h), higher counts were observed under ROS-n conditions than under aerobic conditions, which demonstrate the presence of substantial numbers of sub-lethally injured cells prior to their complete inactivation.

Conclusions

The present study has for the first time confirmed that these bacterial pathogens are inactivated by storage in a copper vessel within 24 h. However, it has also demonstrated that it is necessary to account for short-term sub-lethal injury, manifest as ROS-sensitivity, in order to more fully understand the process. This has important practical implications in terms of the time required to store water within a copper vessel to completely inactivate these bacteria and thereby remove the risk of water-borne disease transmission by this route.
A follow-up study for left ventricular mass on chromosome 12p11 identifies potential candidate genes
Authors: Della-Morte David , Beecham Ashley , Rundek Tatjana , Wang Liyong , McClendon Mark S , Slifer Susan , Blanton Susan H , Di Tullio Marco R , Sacco Ralph L
Published: July 2011

Background

Left ventricular mass (LVM) is an important risk factor for cardiovascular disease. Previously we found evidence for linkage to chromosome 12p11 in Dominican families, with a significant increase in a subset of families with high average waist circumference (WC). In the present study, we use association analysis to further study the genetic effect on LVM.

Methods

Association analysis with LVM was done in the one LOD critical region of the linkage peak in an independent sample of 897 Caribbean Hispanics. Genotype data were available on 7085 SNPs from 23 to 53 MB on chromosome 12p11. Adjustment was made for vascular risk factors and population substructure using an additive genetic model. Subset analysis by WC was performed to test for a difference in genetic effects between the high and low WC subsets.

Results

In the overall analysis, the most significant association was found to rs10743465, downstream of the SOX5 gene (p = 1.27E-05). Also, 19 additional SNPs had nominal p < 0.001. In the subset analysis, the most significant difference in genetic effect between those with high and low WC occurred with rs1157480 (p = 1.37E-04 for the difference in β coefficients), located upstream of TMTC1. Twelve additional SNPs in or near 6 genes had p < 0.001.

Conclusions

The current study supports previously identified evidence by linkage for a genetic effect on LVM on chromosome 12p11 using association analysis in population-based Caribbean Hispanic cohort. SOX5 may play an important role in the regulation of LVM. An interaction of TMTC1 with abdominal obesity may contribute to phenotypic variation of LVM.
Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy
Authors: Maurer Gabriele D , Brucker Daniel P , Bähr Oliver , Harter Patrick N , Hattingen Elke , Walenta Stefan , Mueller-Klieser Wolfgang , Steinbach Joachim P , Rieger Johannes
Published: July 2011

Background

Even in the presence of oxygen, malignant cells often highly depend on glycolysis for energy generation, a phenomenon known as the Warburg effect. One strategy targeting this metabolic phenotype is glucose restriction by administration of a high-fat, low-carbohydrate (ketogenic) diet. Under these conditions, ketone bodies are generated serving as an important energy source at least for non-transformed cells.

Methods

To investigate whether a ketogenic diet might selectively impair energy metabolism in tumor cells, we characterizedin vitroeffects of the principle ketone body 3-hydroxybutyrate in rat hippocampal neurons and five glioma cell lines.In vivo, a non-calorie-restricted ketogenic diet was examined in an orthotopic xenograft glioma mouse model.

Results

The ketone body metabolizing enzymes 3-hydroxybutyrate dehydrogenase 1 and 2 (BDH1 and 2), 3-oxoacid-CoA transferase 1 (OXCT1) and acetyl-CoA acetyltransferase 1 (ACAT1) were expressed at the mRNA and protein level in all glioma cell lines. However, no activation of the hypoxia-inducible factor-1α (HIF-1α) pathway was observed in glioma cells, consistent with the absence of substantial 3-hydroxybutyrate metabolism and subsequent accumulation of succinate. Further, 3-hydroxybutyrate rescued hippocampal neurons from glucose withdrawal-induced cell death but did not protect glioma cell lines. In hypoxia, mRNA expression of OXCT1, ACAT1, BDH1 and 2 was downregulated.In vivo, the ketogenic diet led to a robust increase of blood 3-hydroxybutyrate, but did not alter blood glucose levels or improve survival.

Conclusion

In summary, glioma cells are incapable of compensating for glucose restriction by metabolizing ketone bodiesin vitro, suggesting a potential disadvantage of tumor cells compared to normal cells under a carbohydrate-restricted ketogenic diet. Further investigations are necessary to identify co-treatment modalities, e.g. glycolysis inhibitors or antiangiogenic agents that efficiently target non-oxidative pathways.
Heparin based prophylaxis to prevent venous thromboembolic events and death in patients with cancer - a subgroup analysis of CERTIFY
Authors: Haas Sylvia , Schellong Sebastian M , Tebbe Ulrich , Gerlach Horst-Eberhard , Bauersachs Rupert , Melzer Nima , Abletshauser Claudia , Sieder Christian , Bramlage Peter , Riess Hanno
Published: July 2011

Background

Patients with cancer have an increased risk of VTE. We compared VTE rates and bleeding complications in 1) cancer patients receiving LMWH or UFH and 2) patients with or without cancer.

Methods

Acutely-ill, non-surgical patients ≥70 years with (n = 274) or without cancer (n = 2,965) received certoparin 3,000 UaXa o.d. or UFH 5,000 IU t.i.d. for 8-20 days.

Results

1) Thromboembolic events in cancer patients (proximal DVT, symptomatic non-fatal PE and VTE-related death) occurred at 4.50% with certoparin and 6.03% with UFH (OR 0.73; 95% CI 0.23-2.39). Major bleeding was comparable and minor bleedings (0.75 vs. 5.67%) were nominally less frequent. 7.5% of certoparin and 12.8% of UFH treated patients experienced serious adverse events. 2) Thromboembolic event rates were comparable in patients with or without cancer (5.29 vs. 4.13%) as were bleeding complications. All cause death was increased in cancer (OR 2.68; 95%CI 1.22-5.86). 10.2% of patients with and 5.81% of those without cancer experienced serious adverse events (OR 1.85; 95% CI 1.21-2.81).

Conclusions

Certoparin 3,000 UaXa o.d. and 5,000 IU UFH t.i.d. were equally effective and safe with respect to bleeding complications in patients with cancer. There were no statistically significant differences in the risk of thromboembolic events in patients with or without cancer receiving adequate anticoagulation.

Trial Registration

clinicaltrials.gov, NCT00451412
Big Fish in a Big Pond: a study of academic self concept in first year medical students
Authors: Jackman Kirsty , Wilson Ian G , Seaton Marjorie , Craven Rhonda G
Published: July 2011

Background

Big-fish-little-pond effect (BFLPE) research has demonstrated that students in high-ability environments have lower academic self-concepts than equally able students in low-ability settings. Research has shown low academic self-concepts to be associated with negative educational outcomes. Social comparison processes have been implicated as fundamental to the BFLPE.

Methods

Twenty first-year students in an Australian medical school completed a survey that included academic self-concept and social comparison measures, before and after their first written assessments. Focus groups were also conducted with a separate group of students to explore students' perceptions of competence, the medical school environment, and social comparison processes.

Results

The quantitative study did not reveal any changes in academic self-concept or self-evaluation. The qualitative study suggested that the attributions that students used when discussing performance were those that have been demonstrated to negatively affect self-concept. Students reported that the environment was slightly competitive and they used social comparison to evaluate their performance.

Conclusions

Although the BFLPE was not evident in the quantitative study, results from the qualitative study suggest that the BFLPE might be operating In that students were using attributions that are associated with lower self-concepts, the environment was slightly competitive, and social comparisons were used for evaluation.
Client satisfaction among participants in a randomized trial comparing oral methadone and injectable diacetylmorphine for long-term opioid-dependency
Authors: Marchand Kirsten I , Oviedo-Joekes Eugenia , Guh Daphne , Brissette Suzanne , Marsh David C , Schechter Martin T
Published: July 2011

Background

Substitution with opioid-agonists (e.g., methadone) has shown to be an effective treatment for chronic long-term opioid dependency. Patient satisfaction with treatment has been associated with improved addiction treatment outcomes. However, there is a paucity of studies evaluating patients' satisfaction with Opioid Substitution Treatment (OST). In the present study, participants' satisfaction with OST was evaluated at 3 and 12 months. We sought to test the relationship between satisfaction and patients' characteristics, the treatment modality received and treatment outcomes.

Methods

Data from a randomized controlled trial, the North American Opiate Medication Initiative (NAOMI), conducted in Vancouver and Montreal (Canada) between 2005-2008, was analyzed. The NAOMI study compared the effectiveness of oral methadone vs. injectable diacetylmorphine over 12 months. A small sub-group of patients received injectable hydromorphone on a double blind basis with diacetylmorphine. The Client Satisfaction Questionnaire (CSQ-8) was used to measure satisfaction with treatment. CSQ-8 scores, as well as retention and response to treatment, did not differ between those receiving hydromorphone and diacetylmorphine at 3 or 12 months assessments; therefore, these two groups were analyzed together as the 'injectable' treatment group.

Results

A total of 232 (92%) and 237 (94%) participants completed the CSQ-8 at 3 and 12 months, respectively. Participants in both groups were highly satisfied with treatment. Independent of treatment group, participants satisfied with treatment at 3 months were more likely to be retained at 12 months. Multivariate analysis indicated that satisfaction was greater among those randomized to the injection group after controlling for treatment effectiveness. Participants who were retained, responded to treatment, and had fewer psychological symptoms were more satisfied with treatment. Finally, open-ended comments were made by 149 (60.3%) participants; concerns about the randomization process and the study ending were most commonly reported by participants receiving the oral and injectable medications, respectively.

Conclusions

The higher satisfaction among those receiving medically prescribed injectable diacetylmorphine (or hydromorphone) supports current evidence regarding the attractiveness of this treatment for long-term, opioid-dependent individuals not benefiting sufficiently from other treatments. In addition, the measurement of treatment satisfaction provides valuable information about participants at risk of relapse and in need of additional services.

Trial Registration

ClinicalTrials.gov Identifier: NCT00175357
Proteomic analysis of pregnancy-related proteins from pig uterus endometrium during pregnancy
Authors: Chae Jung-Il , Kim Jumi , Lee Seong G , Jeon Young-Joo , Kim Dong-Wook , Soh Yunjo , Seo Kang S , Lee Hak K , Choi Nag-Jin , Ryu Joohyun , Kang Sunghyun , Cho Seong-Keun , Lee Dong-Seok , Chung Hyung M , Koo and Deog-Bon
Published: July 2011

Many important molecular events associated with implantation and development occur within the female reproductive tract, especially within the uterus endometrium, during pregnancy periods. The endometrium includes the mucosal lining of the uterus, which provides a suitable site for implantation and development of a fertilized egg and fetus. To date, the molecular cascades in the uterus endometrium during pregnancy periods in pigs have not been elucidated fully. In this study, we compared the functional regulated proteins in the endometrium during pregnancy periods with those in non-pregnant conditions and investigated changes in expression patterns during pregnancy (days 40, 70, and 93) using two-dimensional gel electrophoresis (2-DE) and western blotting. The functional regulated proteins were identified and discovered from differentially expressed proteins in the uterus endometrium during pregnancy. We discovered 820 protein spots in a proteomic analysis of uterus endometrium tissues with 2-DE gels. We identified 63 of the 98 proteins regulated differentially among non-pregnant and pregnant tissues (matched and unmatched spots). Interestingly, 10 of these 63 proteins are development-, cytoskeleton- and chaperon-related proteins such as transferrin, protein DJ-1, transgelin, galectin-1, septin 2, stathmin 1, cofilin 1, fascin 1, heat shock protein (HSP) 90β and HSP 27. The specific expression patterns of these proteins in the endometrium during pregnancy were confirmed by western blotting. Our results suggest that the expressions of these genes involved in endometrium function and endometrium development from early to late gestation are associated with the regulation of endometrium development for maintaining pregnancy.
High-precision, large-domain three-dimensional manipulation of nano-materials for fabrication nanodevices
Authors: Zou Rujia , Yu Li , Zhang Zhenyu , Chen Zhigang , Hu Junqing
Published: July 2011

Nanoscaled materials are attractive building blocks for hierarchical assembly of functional nanodevices, which exhibit diverse performances and simultaneous functions. We innovatively fabricated semiconductor nano-probes of tapered ZnS nanowires through melting and solidifying by electro-thermal process; and then, as-prepared nano-probes can manipulate nanomaterials including semiconductor/metal nanowires and nanoparticles through sufficiently electrostatic force to the desired location without structurally and functionally damage. With some advantages of high precision and large domain, we can move and position and interconnect individual nanowires for contracting nanodevices. Interestingly, by the manipulating technique, the nanodevice made of three vertically interconnecting nanowires, i.e., diode, was realized and showed an excellent electrical property. This technique may be useful to fabricate electronic devices based on the nanowires' moving, positioning, and interconnecting and may overcome fundamental limitations of conventional mechanical fabrication.
Nano-embossing technology on ferroelectric thin film Pb(Zr0.3,Ti0.7)O3 for multi-bit storage application
Authors: Shen Zhenkui , Chen Zhihui , Lu Qian , Qiu Zhijun , Jiang Anquan , Qu Xinping , Chen Yifang , Liu Ran
Published: July 2011

In this work, we apply nano-embossing technique to form a stagger structure in ferroelectric lead zirconate titanate [Pb(Zr0.3, Ti0.7)O3 (PZT)] films and investigate the ferroelectric and electrical characterizations of the embossed and un-embossed regions, respectively, of the same films by using piezoresponse force microscopy (PFM) and Radiant Technologies Precision Material Analyzer. Attributed to the different layer thickness of the patterned ferroelectric thin film, two distinctive coercive voltages have been obtained, thereby, allowing for a single ferroelectric memory cell to contain more than one bit of data.
Combinatorial growth of Si nanoribbons
Authors: Park Tae-Eon , Lee Ki-Young , Kim Ilsoo , Chang Joonyeon , Voorhees Peter , Choi Heon-Jin
Published: July 2011

Silicon nanoribbons (Si NRs) with a thickness of about 30 nm and a width up to a few micrometers were synthesized. Systematic observations indicate that Si NRs evolve via the following sequences: the growth of basal nanowires assisted with a Pt catalyst by a vapor-liquid-solid (VLS) mechanism, followed by the formation of saw-like edges on the basal nanowires and the planar filling of those edges by a vapor-solid (VS) mechanism. Si NRs have twins along the longitudinal < 110 > growth of the basal nanowires that also extend in < 112 > direction to edge of NRs. These twins appear to drive the lateral growth by a reentrant twin mechanism. These twins also create a mirror-like crystallographic configuration in the anisotropic surface energy state and appear to further drive lateral saw-like edge growth in the < 112 > direction. These outcomes indicate that the Si NRs are grown by a combination of the two mechanisms of a Pt-catalyst-assisted VLS mechanism for longitudinal growth and a twin-assisted VS mechanism for lateral growth.
Room-temperature nonequilibrium growth of controllable ZnO nanorod arrays
Authors: Li Qian , Cheng Kui , Weng Wenjian , Song Chenlu , Du Piyi , Shen Ge , Han Gaorong
Published: July 2011

In this study, controllable ZnO nanorod arrays were successfully synthesized on Si substrate at room temperature (approx. 25°C). The formation of controllable ZnO nanorod arrays has been investigated using growth media with different concentrations and molar ratios of Zn(NO3)2 to NaOH. Under such a nonequilibrium growth condition, the density and dimension of ZnO nanorod arrays were successfully adjusted through controlling the supersaturation degree, i.e., volume of growth medium. It was found that the wettability and electrowetting behaviors of ZnO nanorod arrays could be tuned through variations of nanorods density and length. Moreover, its field emission property was also optimized by changing the nanorods density and dimension.
Formation of translational risk score based on correlation coefficients as an alternative to Cox regression models for predicting outcome in patients with NSCLC
Authors: Kössler Wolfgang , Fiebeler Anette , Willms Arnulf , ElAidi Tina , Klosterhalfen Bernd , Klinge Uwe
Published: July 2011

Background

Personalised cancer therapy, such as that used for bronchial carcinoma (BC), requires treatment to be adjusted to the patient's status. Individual risk for progression is estimated from clinical and molecular-biological data using translational score systems. Additional molecular information can improve outcome prediction depending on the marker used and the applied algorithm. Two models, one based on regressions and the other on correlations, were used to investigate the effect of combining various items of prognostic information to produce a comprehensive score. This was carried out using correlation coefficients, with options concerning a more plausible selection of variables for modelling, and this is considered better than classical regression analysis.

Methods

Clinical data concerning 63 BC patients were used to investigate the expression pattern of five tumour-associated proteins. Significant impact on survival was determined using log-rank tests. Significant variables were integrated into a Cox regression model and a new variable called integrative score of individual risk (ISIR), based on Spearman's correlations, was obtained.

Results

High tumour stage (TNM) was predictive for poor survival, while CD68 and Gas6 protein expression correlated with a favourable outcome. Cox regression model analysis predicted outcome more accurately than using each variable in isolation, and correctly classified 84% of patients as having a clear risk status. Calculation of the integrated score for an individual risk (ISIR), considering tumour size (T), lymph node status (N), metastasis (M), Gas6 and CD68 identified 82% of patients as having a clear risk status.

Conclusion

Combining protein expression analysis of CD68 and GAS6 with T, N and M, using Cox regression or ISIR, improves prediction. Considering the increasing number of molecular markers, subsequent studies will be required to validate translational algorithms for the prognostic potential to select variables with a high prognostic power; the use of correlations offers improved prediction.
An overview of Triple infection with Hepatitis B, C and D viruses
Authors: Riaz Mehwish , Idrees Muhamad , Kanwal Hifza , Kabir Firoz
Published: July 2011

Viral hepatitis is one of the major health problems worldwide, particularly in South East Asian countries including Pakistan where hepatitis C virus (HCV) and hepatitis B virus (HBV) infections are highly endemic. Hepatitis delta virus (HDV) is also not uncommon world-wide. HCV, HBV, and HDV share parallel routes of transmission due to which dual or triple viral infection can occur in a proportion of patients at the same time. HBV and HCV are important factors in the development of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). In addition to LC and HCC, chronic HDV infection also plays an important role in liver damage with oncogenic potential.

The current article reviews the available literature about the epidemiology, pathogenesis, transmission, symptoms, diagnosis, replication, disease outcome, treatment and preventive measures of triple hepatitis infection by using key words; epidemiology of triple infection, risk factors, awareness status, treatment and replication cycle in PubMed, PakMediNet, Directory of Open Access Journals (DOAJ) and Google Scholar. Total data from 74 different studies published from 1983 to 2010 on triple hepatitis infections were reviewed and included in this study. The present article briefly describes triple infection with HCV, HBV and HDV.
Development of an optimized method for the detection of airborne viruses with real-time PCR analysis
Authors: Ziros Panos G , Kokkinos Petros A , Legaki Euaggelia , Vantarakis Apostolos
Published: July 2011

Background

Airborne viruses remain one of the major public health issues worldwide. Detection and quantification of airborne viruses is essential in order to provide information regarding public health risk assessment.

Findings

In this study, an optimized new, simple, low cost method for sampling of airborne viruses using Low Melting Agarose (LMA) plates and a conventional microbial air sampling device has been developed. The use of LMA plates permits the direct nucleic acids extraction of the captured viruses without the need of any preliminary elution step. Molecular detection and quantification of airborne viruses is performed using real-time quantitative (RT-)PCR (Q(RT-)PCR) technique. The method has been tested using Adenoviruses (AdVs) and Noroviruses (NoVs) GII, as representative DNA and RNA viruses, respectively. Moreover, the method has been tested successfully in outdoor experiments, by detecting and quantifying human adenoviruses (HAdVs) in the airborne environment of a wastewater treatment plant.

Conclusions

The great advantage of LMA is that nucleic acids extraction is performed directly on the LMA plates, while the eluted nucleic acids are totally free of inhibitory substances. Coupled with QPCR the whole procedure can be completed in less than three (3) hours.
Improved functionality, health related quality of life and decreased burden of disease in patients with ADHD treated with OROS® MPH: is treatment response different between children and adolescents?
Authors: Berek Michael , Kordon Andreas , Hargarter Ludger , Mattejat Fritz , Slawik Lara , Rettig Klaus , Schäuble Barbara
Published: July 2011

Background

To compare clinical and health-related quality of life (HRQoL) outcomes between children and adolescents with ADHD treated with OROS® MPH, using data from two large similarly-designed multicenter, prospective, open-label, single-arm, non-interventional studies.

Methods

Pooled analysis (42603ATT4037, 42603 - ATT - 4001) including patients (6 to 18 years) with a confirmed diagnosis of ADHD. Patients were treated with OROS® MPH for 12 weeks; ADHD symptoms, functioning, HRQoL, safety and tolerability parameters were assessed.

Results

822 patients (583 children [6-12 years], 239 adolescents [13-18 years]) were included in the pooled analysis. Mean daily OROS® MPH starting doses in the child and adolescent subgroups were 29.0 ± 11.7 and 37.6 ± 15.6 mg, respectively (p < 0.001). At study end (week 12), the overall mean daily dose was 35.5 ± 14.0 mg, with children and adolescents receiving 32.8 ± 12.7 and 42.0 ± 15.1 mg/day, respectively (p < 0.001). Significant (p < 0.0001: overall population, children, adolescents) symptomatic, functional and HRQoL improvements were observed from baseline to study end using the Conners' Parents Rating Scale (overall: 29.2 ± 10.7 [baseline] to 19.3 ± 11.3 [endpoint]), Children's Global Assessment Scale (overall: 58.5 ± 14.5 [baseline] to 69.6 ± 16.1 [endpoint]), and ILC-LQ0-28. At week 12, between-age group differences were seen in the individual ILC-LQ0-28 parameters: school performance (p = 0.001 [parents' assessment], p = 0.032 [childrens' assessment]), global QoL (p = 0.012 [parents']) and interests and hobbies (p = 0.023 [childrens']). Treating physician's planned continued use of OROS® MPH in 76.9%, 86.0% and 79.3% of children, adolescents and the total population, respectively, at study end (p = 0.029 between-age subgroups). 195 of 822 patients (23.7%) experienced at least one treatment-emergent adverse event; most commonly reported AEs in the total group (≥4%) were insomnia (7.2%), anorexia (4.3%) and involuntary muscle contractions (4.1%). No clinically relevant changes in body weight or vital signs were observed.

Conclusions

Clinically relevant differences between children and adolescents with ADHD are present. Adolescents appeared to have a lower health related quality of life and functioning compared to children at baseline, however, they were able to reach comparable ratings at endpoint for most items. Similarly, burden of disease decreased in patients and their carers. OROS MPH was generally safe and well tolerated.
Molecular characterization of cathepsin B from Clonorchis sinensis excretory/secretory products and assessment of its potential for serodiagnosis of clonorchiasis
Authors: Chen Wenjun , Wang Xiaoyun , Li Xuerong , Lv Xiaoli , Zhou Chenhui , Deng Chuanhuan , Lei Huali , Men Jingtao , Fan Yongxiu , Liang Chi , Yu Xinbing
Published: July 2011

Background

Cathepsin cysteine proteases play multiple roles in the life cycle of parasites such as food uptake, immune invasion and pathogenesis, making them valuable targets for diagnostic assays, vaccines and drugs. The purpose of this study was to identify a cathepsin B of Clonorchis sinensis (Cs CB) and to investigate its diagnostic value for human helminthiases.

Results

The predicted amino acid sequence of the cathepsin B of C. sinensis shared 63%, 52%, 50% identity with that of Schistosoma japonicum, Homo sapiens and Fasciola hepatica, respectively. Sequence encoding proenzyme of Cs CB was overexpressed in Escherichia coli. Reverse transcription PCR experiments revealed that Cs CB transcribed in both adult worm and metacercaria of C. sinensis. Cs CB was identified as a C. sinensis excretory/secretory product by immunoblot assay, which was consistent with immunohistochemical localization showing that Cs CB was especially expressed in the intestine of C. sinensis adults. Both ELISA and western blotting analysis showed recombinant Cs CB could react with human sera from clonorchiasis and other helminthiases.

Conclusions

Our findings revealed that secreted CsCB may play an important role in the biology of C. sinensis and could be a diagnostic candidate for helminthiases.
Adjuvant chemoradiotherapy for locoregionally advanced and high-risk salivary gland malignancies
Authors: Pederson Aaron W , Salama Joseph K , Haraf Daniel J , Witt Mary Ellen , Stenson Kerstin M , Portugal Louis , Seiwert Tanguy , Villaflor Victoria M , Cohen Ezra EW , Vokes Everett E , Blair Elizabeth A
Published: July 2011

Background

To report the outcomes of patients with locoregionally advanced and high- risk salivary gland malignancies treated with surgery followed by adjuvant chemoradiotherapy.

Methods

From 09/1991 - 06/2007, 24 high-risk salivary gland cancer patients were treated with surgery, followed by adjuvant chemoradiotherapy for high-risk pathologic features including, perineural involvement, nodal involvement, positive margins, or T3/T4 tumors. Chemoradiotherapy was delivered for 4-6 alternating week cycles: the most common regimen, TFHX, consisted of 5 days paclitaxel (100 mg/m2 on d1), infusional 5-fluorouracil (600 mg/m2/d × 5d), hydroxyurea (500 mg PO BID), and 1.5 Gy twice daily irradiation followed by a 9-day break without treatment.

Results

Median follow-up was 42 months. The parotid gland was more frequently involved (n = 17) than minor (n = 4) or submandibular (n = 3) glands. The median radiation dose was 65 Gy (range 55-68 Gy). Acute treatment related toxicity included 46% grade 3 mucositis and 33% grade 3 hematologic toxicity. Six patients required feeding tubes during treatment. One patient progressed locally, 8 patients progressed distantly, and none progressed regionally. Five-year locoregional progression free survival was 96%. The 3 and 5 year overall survival was 79% and 59%, respectively. Long-term complications included persistent xerostomia (n = 5), esophageal stricture requiring dilatation (n = 1), and tempromandibular joint syndrome (n = 1).

Conclusions

Surgical resection followed by adjuvant chemoradiotherapy results in promising locoregional control for high-risk salivary malignancy patients.
Decreases in serum levels of S100A8/9 (calprotectin) correlate with improvements in total swollen joint count in patients with recent-onset rheumatoid arthritis
Authors: Andrés Cerezo Lucie , Mann Heřman , Pecha Ondřej , Pleštilová Lenka , Pavelka Karel , Vencovský Jiří , Šenolt Ladislav
Published: July 2011

Introduction

The aim of this study was to examine the serum levels of S100 proteins and to evaluate their role in patients with recent-onset rheumatoid arthritis (RA).

Methods

Serum levels of S100A8/9 and S100A12 were analysed in 43 patients with recent-onset RA, both before and three months after the initiation of conventional treatment, as well as in 32 healthy individuals. Disease activity was assessed based on serum levels of C-reactive protein (CRP), the Disease Activity Score for 28 joints (DAS28) and the total number of swollen joints count for 66 joints (SJC).

Results

The levels of serum S100A8/9 and S100A12 were significantly higher in patients with recent-onset RA compared to the levels in healthy individuals (P < 0.0001) and normalised after three months of treatment. Using age- and sex-adjusted analysis, S100A8/9 levels were correlated with CRP (r = 0.439, P < 0.01), DAS28 (r = 0.501, P = 0.002) and SJC (r = 0.443, P = 0.007), while S100A12 was less significantly correlated with these parameters. Higher levels of S100A8/9 at baseline predicted improvement in the levels of CRP and SJC over time. Moreover, decreases in serum S100A8/9 were associated with decreased serum levels of CRP (r = 0.459, P = 0.005) and improvements in SJC (r = 0.459, P = 0.005). In multiple linear regression analyses, decreases in S100A8/9 but not CRP were significant predictors for improvements in SJC (P = 0.001).

Conclusions

This study is the first to show normalisation of elevated S100 proteins in patients with recent-onset RA after the initiation of conventional treatment. Therefore, S100A8/9 might potentially be a predictive marker for improvement in the total number of swollen joints in patients in the early phase of RA.
Serum 25-hydroxyvitamin D and postmenopausal breast cancer survival: a prospective patient cohort study
Authors: Vrieling Alina , Hein Rebecca , Abbas Sascha , Schneeweiss Andreas , Flesch-Janys Dieter , Chang-Claude Jenny
Published: July 2011

Introduction

Vitamin D has been postulated to be involved in cancer prognosis. Thus far, only two studies reported on its association with recurrence and survival after breast cancer diagnosis yielding inconsistent results. Therefore, the aim of our study was to assess the effect of post-diagnostic serum 25-hydroxyvitamin D [25(OH)D] concentrations on overall survival and distant disease-free survival.

Methods

We conducted a prospective cohort study in Germany including 1,295 incident postmenopausal breast cancer patients aged 50-74 years. Patients were diagnosed between 2002 and 2005 and median follow-up was 5.8 years. Cox proportional hazards models were stratified by age at diagnosis and season of blood collection and adjusted for other prognostic factors. Fractional polynomials were used to assess the true dose-response relation for 25(OH)D.

Results

Lower concentrations of 25(OH)D were linearly associated with higher risk of death (hazard ratio (HR) = 1.08 per 10 nmol/L decrement; 95% confidence interval (CI), 1.00 to 1.17) and significantly higher risk of distant recurrence (HR = 1.14 per 10 nmol/L decrement; 95%CI, 1.05 to 1.24). Compared with the highest tertile (≥ 55 nmol/L), patients within the lowest tertile (< 35 nmol/L) of 25(OH)D had a HR for overall survival of 1.55 (95%CI, 1.00 to 2.39) and a HR for distant disease-free survival of 2.09 (95%CI, 1.29 to 3.41). In addition, the association with overall survival was found to be statistically significant only for 25(OH)D levels of blood samples collected before start of chemotherapy but not for those of samples taken after start of chemotherapy (P for interaction = 0.06).

Conclusions

In conclusion, lower serum 25(OH)D concentrations may be associated with poorer overall survival and distant disease-free survival in postmenopausal breast cancer patients.