bluuebunny/crossref_metadata_2025 huggingface dataset:
An Assessment of the Energy and Resource-efficient Hybrid Composite Beams for Multi-residential Apartments
Authors: Hong Won-Kee , Yune Dai-Young , Park Seon-Chee , Yoon Tae-Ho
Published: November 2010

Apartments with load-bearing wall construction are used extensively in Korea, but have the disadvantage of a short life, causing serious economic losses in terms of construction waste, materials and energy consumption. This paper presents the findings on multi-residential apartments that utilise a hybrid composite frame as a viable alternative for the energy efficiency associated with construction materials. The hybrid composite frame consists of a structural tee, reinforcement steels and pre-cast concrete. The use of the hybrid composite frame reduces the overall amount of energy consumption. In addition, multi-residential apartments utilising a hybrid composite frame have advantages such as flexibility in planning and easier repair and remodelling. This study investigates tower-shape, multi-residential apartments of various heights and floor areas to compare the energy efficiency of the hybrid composite system with that of the bearing wall system. The multi-residential apartments that utilise the hybrid composite frame are analysed in terms of both reduced principal materials and reduced energy consumption compared with apartments of a load-bearing wall structure. Rapid demand for long life and multi-residential apartment construction is expected.
Supporting Students Who Are Deaf or Hard of Hearing in General Education Classrooms
Authors: Berndsen Maura , Luckner John
Published: November 2010

The majority of students who are deaf or hard of hearing currently receive educational services in general education settings. Trends that have led to this shift in placement as well as potential benefits and barriers are presented. A unique partnership between the Washington State Center for Childhood Deafness and Hearing Loss (formerly the Washington School for the Deaf) and Listen and Talk created to help local, school-based teams effectively provide services to students with a hearing loss who want to develop listening and spoken language skills is described. Specifics of the collaborative process, data collection procedures, and accommodations for students are included.
DEVSim++ Toolset for Defense Modeling and Simulation and Interoperation
Authors: Tag Gon Kim  , Chang Ho Sung  , Hong Su-Youn , Jeong Hee Hong  , Chang Beom Choi  , Jeong Hoon Kim  , Kyung Min Seo  , Jang Won Bae
Published: November 2010

Discrete Event Systems Specification (DEVS) formalism supports the specification of discrete event models in a hierarchical and modular manner. Efforts have been made to develop the simulation environments for the modeling and simulation (M&S) of systems using DEVS formalism, particularly in defense M&S domains. This paper introduces the DEVSim++ toolset and its applications. The Object-Analysis Index (OAI) matrix is a tabular form of objects and analysis indices for requirements analysis. DEVSim++ is a realization of DEVS formalism in C++ for M&S. VeriTool is a DEVS model verification tool. DEVSimHLA is a library to support High-level Architecture (HLA) in DEVSim++. Other tools, including KComLib, FOM2CPPClass, and KHLAAdaptor, are used to develop a smart adaptor that allows for the interoperation of simulators of any kind. PlugSim is a distributed simulation framework using plug-in methods. These tools are utilized in every stage of the M&S development process, as well as in every application of the M&S missions to the military domain. Accordingly, the applications implemented by the toolset are used in the training, analytic, and acquisition missions of the Republic of Korea military branches. We expect the DEVS applications to become more prolific as M&S demands grow, and our toolset is already proven as complete and efficient in the domain of defense M&S.
Appreciative inquiry: a strength-based research approach to building Canadian public health nursing capacity
Authors: Knibbs Kristin , Underwood Jane , MacDonald Mary , Schoenfeld Bonnie , Lavoie-Tremblay Mélanie , Crea-Arsenio Mary , Meagher-Stewart Donna , Leeseberg Stamler Lynnette , Blythe Jennifer , Ehrlich Anne
Published: November 2010

In this paper we evaluate the use of appreciative inquiry in focus groups with public health nurses, managers and policy makers across Canada as part of our project to generate policy recommendations for building public health nursing capacity. The focus group protocol successfully involved participants in data collection and analysis through a unique combination of appreciative inquiry and nominal group process. This approach resulted in credible data for analysis, and the final analysis met scientific research standards. The evaluation revealed that our process was effective in engaging participants when their time available was limited, no matter what their position or public health setting, and in eliciting solution-focused results. By focusing on what works well in an organisation, appreciative inquiry enabled us to identify the positive attributes of organisations that best support public health nursing practice and to develop practical policy recommendations because they were based on participants’ experience. Further, appreciative inquiry was especially effective with public health policy makers and nurses as it is consistent with the strength-based, capacity building approaches inherent in public health nursing practice.
Perceived Partner Responsiveness Minimizes Defensive Reactions to Failure
Authors: Caprariello Peter A. , Reis Harry T.
Published: November 2010

Can thinking about responsive relationships increase openness to failure? Study 1 tested whether subliminally priming responsiveness would increase accessibility of words associated with a failed intelligence test. Compared to participants primed with acquaintances or nonsense letters, participants primed with responsive partners were quicker to recognize words associated with failure and did so more accurately, suggesting lesser defensiveness. Study 2 tested whether supraliminally priming responsiveness would decrease self-handicapping on a difficult and potentially embarrassing task. Compared to participants who thought about friends or acquaintances, participants who thought about responsive relationships claimed less external interference with their abilities. These findings indicate that relationships characterized by understanding and validation may promote nondefensive reactions to real or potential failure.
Anticipation in familial hematologic malignancies
Authors: Tegg Elizabeth M. , Thomson Russell J. , Stankovich Jim M. , Banks Annette , Marsden Katherine A. , Lowenthal Ray M. , Foote Simon J. , Dickinson Joanne L.
Published: November 2010

We describe a collection of 11 families with ≥ 2 generations of family members whose condition has been diagnosed as a hematologic malignancy. In 9 of these families there was a significant decrease in age at diagnosis in each subsequent generation (anticipation). The mean age at diagnosis in the first generation was 67.8 years, 57.1 years in the second, and 41.8 years in the third (P < .0002). This was confirmed in both direct parent-offspring pairs with a mean reduction of 19 years in the age at diagnosis (P = .0087) and when the analysis was repeated only including cases of mature B-cell neoplasm (P = .0007). We believe that these families provide further insight into the nature of the underlying genetic mechanism of predisposition in these families.
Global genome analysis of the shikimic acid pathway reveals greater gene loss in host-associated than in free-living bacteria
Authors: Zucko Jurica , Dunlap Walter C , Shick J Malcolm , Cullum John , Cercelet François , Amin Bijal , Hammen Lena , Lau Timothy , Williams Jamal , Hranueli Daslav , Long Paul F
Published: November 2010

Background

A central tenet in biochemistry for over 50 years has held that microorganisms, plants and, more recently, certain apicomplexan parasites synthesize essential aromatic compounds via elaboration of a complete shikimic acid pathway, whereas metazoans lacking this pathway require a dietary source of these compounds. The large number of sequenced bacterial and archaean genomes now available for comparative genomic analyses allows the fundamentals of this contention to be tested in prokaryotes. Using Hidden Markov Model profiles (HMM profiles) to identify all known enzymes of the pathway, we report the presence of genes encoding shikimate pathway enzymes in the hypothetical proteomes constructed from the genomes of 488 sequenced prokaryotes.

Results

Amongst free-living prokaryotes most Bacteria possess, as expected, genes encoding a complete shikimic acid pathway, whereas of the culturable Archaea, only one was found to have a complete complement of recognisable enzymes in its predicted proteome. It may be that in the Archaea, the primary amino-acid sequences of enzymes of the pathway are highly divergent and so are not detected by HMM profiles. Alternatively, structurally unrelated (non-orthologous) proteins might be performing the same biochemical functions as those encoding recognized genes of the shikimate pathway. Most surprisingly, 30% of host-associated (mutualistic, commensal and pathogenic) bacteria likewise do not possess a complete shikimic acid pathway. Many of these microbes show some degree of genome reduction, suggesting that these host-associated bacteria might sequester essential aromatic compounds from a parasitised host, as a 'shared metabolic adaptation' in mutualistic symbiosis, or obtain them from other consorts having the complete biosynthetic pathway. The HMM results gave 84% agreement when compared against data in the highly curated BioCyc reference database of genomes and metabolic pathways.

Conclusions

These results challenge the conventional belief that the shikimic acid pathway is universal and essential in prokaryotes. The possibilities that non-orthologous enzymes catalyse reactions in this pathway (especially in the Archaea), or that there exist specific uptake mechanisms for the acquisition of shikimate intermediates or essential pathway products, warrant further examination to better understand the precise metabolic attributes of host-beneficial and pathogenic bacteria.
In silico analysis highlights the frequency and diversity of type 1 lantibiotic gene clusters in genome sequenced bacteria
Authors: Marsh Alan J , O'Sullivan Orla , Ross R Paul , Cotter Paul D , Hill Colin
Published: November 2010

Background

Lantibiotics are lanthionine-containing, post-translationally modified antimicrobial peptides. These peptides have significant, but largely untapped, potential as preservatives and chemotherapeutic agents. Type 1 lantibiotics are those in which lanthionine residues are introduced into the structural peptide (LanA) through the activity of separate lanthionine dehydratase (LanB) and lanthionine synthetase (LanC) enzymes. Here we take advantage of the conserved nature of LanC enzymes to devise an in silico approach to identify potential lantibiotic-encoding gene clusters in genome sequenced bacteria.

Results

In total 49 novel type 1 lantibiotic clusters were identified which unexpectedly were associated with species, genera and even phyla of bacteria which have not previously been associated with lantibiotic production.

Conclusions

Multiple type 1 lantibiotic gene clusters were identified at a frequency that suggests that these antimicrobials are much more widespread than previously thought. These clusters represent a rich repository which can yield a large number of valuable novel antimicrobials and biosynthetic enzymes.
Effect of colony morphology variation of Burkholderia pseudomallei on intracellular survival and resistance to antimicrobial environments in human macrophages in vitro
Authors: Tandhavanant Sarunporn , Thanwisai Aunchalee , Limmathurotsakul Direk , Korbsrisate Sunee , Day Nicholas PJ , Peacock Sharon J , Chantratita Narisara
Published: November 2010

Background

Primary diagnostic cultures from patients with melioidosis demonstrate variation in colony morphology of the causative organism, Burkholderia pseudomallei. Variable morphology is associated with changes in the expression of a range of putative virulence factors. This study investigated the effect of B. pseudomallei colony variation on survival in the human macrophage cell line U937 and under laboratory conditions simulating conditions within the macrophage milieu. Isogenic colony morphology types II and III were generated from 5 parental type I B. pseudomallei isolates using nutritional limitation. Survival of types II and III were compared with type I for all assays.

Results

Morphotype was associated with survival in the presence of H2O2 and antimicrobial peptide LL-37, but not with susceptibility to acid, acidified sodium nitrite, or resistance to lysozyme, lactoferrin, human neutrophil peptide-1 or human beta defensin-2. Incubation under anaerobic conditions was a strong driver for switching of type III to an alternative morphotype. Differences were noted in the survival and replication of the three types following uptake by human macrophages, but marked strain-to strain-variability was observed. Uptake of type III alone was associated with colony morphology switching.

Conclusions

Morphotype is associated with phenotypes that alter the ability of B. pseudomallei to survive in adverse environmental conditions.
Temperature-dependent phenotypic variation of Campylobacter jejuni lipooligosaccharides
Authors: Semchenko Evgeny A , Day Christopher J , Wilson Jennifer C , Grice I Darren , Moran Anthony P , Korolik Victoria
Published: November 2010

Background

Campylobacter jejuni is a major bacterial cause of food-borne enteritis, and its lipooligosaccharide (LOS) plays an initiating role in the development of the autoimmune neuropathy, Guillain-Barré syndrome, by induction of anti-neural cross-reactive antibodies through ganglioside molecular mimicry.

Results

Herein we describe the existence and heterogeneity of multiple LOS forms in C. jejuni strains of human and chicken origin grown at 37°C and 42°C, respectively, as determined on sodium dodecyl sulphate-polyacrylamide electrophoresis gels with carbohydrate-specific silver staining and blotting with anti-ganglioside ligands, and confirmed by nuclear magnetic resonance (NMR) spectroscopy. The C. jejuni NCTC 11168 original isolate (11168-O) was compared to its genome-sequenced variant (11168-GS), and both were found to have a lower-Mr LOS form, which was different in size and structure to the previously characterized higher-Mr form bearing GM1 mimicry. The lower-Mr form production was found to be dependent on the growth temperature as the production of this form increased from ~5%, observed at 37°C to ~35% at 42°C. The structure of the lower-Mr form contained a β-D-Gal-(1→3)-β-D-GalNAc disaccharide moiety which is consistent with the termini of the GM1, asialo-GM1, GD1, GT1 and GQ1 gangliosides, however, it did not display GM1 mimicry as assessed in blotting studies but was shown in NMR to resemble asialo-GM1. The production of multiple LOS forms and lack of GM1 mimicry was not a result of phase variation in the genes tested of NCTC 11168 and was also observed in most of the human and chicken isolates of C. jejuni tested.

Conclusion

The presence of differing amounts of LOS forms at 37 and 42°C, and the variety of forms observed in different strains, indicate that LOS form variation may play a role in an adaptive mechanism or a stress response of the bacterium during the colonization of different hosts.
Gene expression profile analysis of genes in rat hippocampus from antidepressant treated rats using DNA microarray
Authors: Lee Jun-Ho , Ko Eunjung , Kim Young-Eun , Min Ji-Young , Liu Jian , Kim Yangseok , Shin Minkyu , Hong Moochang , Bae Hyunsu
Published: November 2010

Background

The molecular and biological mechanisms by which many antidepressants function are based on the monoamine depletion hypothesis. However, the entire cascade of mechanisms responsible for the therapeutic effect of antidepressants has not yet been elucidated.

Results

We used a genome-wide microarray system containing 30,000 clones to evaluate total RNA that had been isolated from the brains of treated rats to identify the genes involved in the therapeutic mechanisms of various antidepressants, a tricyclic antidepressant (imipramine). a selective serotonin reuptake inhibitor (fluoxetine), a monoamine oxidase inhibitor (phenelzine) and psychoactive herbal extracts of Nelumbinis Semen (NS). To confirm the differential expression of the identified genes, we analyzed the amount of mRNA that was isolated from the hippocampus of rats that had been treated with antidepressants by real-time RT-PCR using primers specific for selected genes of interest. These data demonstrate that antidepressants interfere with the expression of a large array of genes involved in signaling, survival and protein metabolism, suggesting that the therapeutic effect of these antidepressants is very complex. Surprisingly, unlike other antidepressants, we found that the standardized herbal medicine, Nelumbinis Semen, is free of factors that can induce neurodegenerative diseases such as caspase 8, α-synuclein, and amyloid precursor protein. In addition, the production of the inflammatory cytokine, IFNγ, was significantly decreased in rat hippocampus in response to treatment with antidepressants, while the inhibitory cytokine, TGFβ, was significantly enhanced.

Conclusions

These results suggest that antidepressants function by regulating neurotransmission as well as suppressing immunoreactivity in the central nervous system.
Identification of seed proteins associated with resistance to pre-harvested aflatoxin contamination in peanut (Arachis hypogaea L)
Authors: Wang Tong , Zhang Erhua , Chen Xiaoping , Li Ling , Liang Xuanqiang
Published: November 2010

Background

Pre-harvest infection of peanuts byAspergillus flavusand subsequent aflatoxin contamination is one of the food safety factors that most severely impair peanut productivity and human and animal health, especially in arid and semi-arid tropical areas. Some peanut cultivars with natural pre-harvest resistance to aflatoxin contamination have been identified through field screening. However, little is known about the resistance mechanism, which has slowed the incorporation of resistance into cultivars with commercially acceptable genetic background. Therefore, it is necessary to identify resistance-associated proteins, and then to recognize candidate resistance genes potentially underlying the resistance mechanism.

Results

The objective of this study was to identify resistance-associated proteins in response toA. flavusinfection under drought stress using two-dimensional electrophoresis with mass spectrometry. To identify proteins involved in the resistance to pre-harvest aflatoxin contamination, we compared the differential expression profiles of seed proteins between a resistant cultivar (YJ-1) and a susceptible cultivar (Yueyou 7) under well-watered condition, drought stress, andA. flavusinfection with drought stress. A total of 29 spots showed differential expression between resistant and susceptible cultivars in response toA. flavusattack under drought stress. Among these spots, 12 protein spots that consistently exhibited an altered expression were screened by Image Master 5.0 software and successfully identified by MALDI-TOF MS. Five protein spots, including Oso7g0179400, PII protein, CDK1, Oxalate oxidase, SAP domain-containing protein, were uniquely expressed in the resistant cultivar. Six protein spots including low molecular weight heat shock protein precursor, RIO kinase, L-ascorbate peroxidase, iso-Ara h3, 50 S ribosomal protein L22 and putative 30 S ribosomal S9 were significantly up-regulated in the resistant cultivar challenged byA. flavusunder drought stress. A significant decrease or down regulation of trypsin inhibitor caused byA. flavusin the resistant cultivar was also observed. In addition, variations in protein expression patterns for resistant and susceptible cultivars were further validated by real time RT-PCR analysis.

Conclusion

In summary, this study provides new insights into understanding of the molecular mechanism of resistance to pre-harvest aflatoxin contamination in peanut, and will help to develop peanut varieties with resistance to pre-harvested aflatoxin contamination.
Recombinant Expression Screening of P. aeruginosaBacterial Inner Membrane Proteins
Authors: Madhavan Vidya , Bhatt Forum , Jeffery Constance J
Published: November 2010

Background

Transmembrane proteins (TM proteins) make up 25% of all proteins and play key roles in many diseases and normal physiological processes. However, much less is known about their structures and molecular mechanisms than for soluble proteins. Problems in expression, solubilization, purification, and crystallization cause bottlenecks in the characterization of TM proteins. This project addressed the need for improved methods for obtaining sufficient amounts of TM proteins for determining their structures and molecular mechanisms.

Results

Plasmid clones were obtained that encode eighty-seven transmembrane proteins with varying physical characteristics, for example, the number of predicted transmembrane helices, molecular weight, and grand average hydrophobicity (GRAVY). All the target proteins were fromP. aeruginosa, a gram negative bacterial opportunistic pathogen that causes serious lung infections in people with cystic fibrosis. The relative expression levels of the transmembrane proteins were measured under several culture growth conditions. The use ofE. colistrains, a T7 promoter, and a 6-histidine C-terminal affinity tag resulted in the expression of 61 out of 87 test proteins (70%). In this study, proteins with a higher grand average hydrophobicity and more transmembrane helices were expressed less well than less hydrophobic proteins with fewer transmembrane helices.

Conclusions

In this study, factors related to overall hydrophobicity and the number of predicted transmembrane helices correlated with the relative expression levels of the target proteins. Identifying physical characteristics that correlate with protein expression might aid in selecting the "low hanging fruit", or proteins that can be expressed to sufficient levels using anE. coliexpression system. The use of other expression strategies or host species might be needed for sufficient levels of expression of transmembrane proteins with other physical characteristics. Surveys like this one could aid in overcoming the technical bottlenecks in working with TM proteins and could potentially aid in increasing the rate of structure determination.
A TaqMan real-time PCR assay for the detection and quantitation of Plasmodium knowlesi
Authors: Divis Paul CS , Shokoples Sandra E , Singh Balbir , Yanow Stephanie K
Published: November 2010

Background

The misdiagnosis of Plasmodium knowlesi by microscopy has prompted a re-evaluation of the geographic distribution, prevalence and pathogenesis of this species using molecular diagnostic tools. In this report, a specific probe for P. knowlesi, that can be used in a previously described TaqMan real-time PCR assay for detection of Plasmodium spp., and Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae and Plasmodium ovale, was designed and validated against clinical samples.

Methods

A hydrolysis probe for a real-time PCR assay was designed to recognize a specific DNA sequence within the P. knowlesi small subunit ribosomal RNA gene. The sensitivity, linearity and specificity of the assay were determined using plasmids containing P. knowlesi DNA and genomic DNA of P. falciparum, P. knowlesi, P. malariae, P. ovale and P. vivax isolated from clinical samples. DNA samples of the simian malaria parasites Plasmodium cynomolgi and Plasmodium inui that can infect humans under experimental conditions were also examined together with human DNA samples.

Results

Analytical sensitivity of the P. knowlesi-specific assay was 10 copies/μL and quantitation was linear over a range of 10-106 copies. The sensitivity of the assay is equivalent to nested PCR and P. knowlesi DNA was detected from all 40 clinical P. knowlesi specimens, including one from a patient with a parasitaemia of three parasites/μL of blood. No cross-reactivity was observed with 67 Plasmodium DNA samples (31 P. falciparum, 23 P. vivax, six P. ovale, three P. malariae, one P. malariae/P. ovale, one P. falciparum/P. malariae, one P. inui and one P. cynomolgi) and four samples of human DNA.

Conclusions

This test demonstrated excellent sensitivity and specificity, and adds P. knowlesi to the repertoire of Plasmodium targets for the clinical diagnosis of malaria by real-time PCR assays. Furthermore, quantitation of DNA copy number provides a useful advantage over other molecular assays to investigate the correlation between levels of infection and the spectrum of disease.
Structure of HIV-1 quasi-species as early indicator for switches of co-receptor tropism
Authors: Dybowski Nikolaj , Heider Dominik , Hoffmann Daniel
Published: November 2010

Deep sequencing is able to generate a complete picture of the retroviral quasi-species in a patient. We demonstrate that the unprecedented power of deep sequencing in conjunction with computational data analysis has great potential for clinical diagnostics and basic research. Specifically, we analyzed longitudinal deep sequencing data from patients in a study with Vicriviroc, a drug that blocks the HIV-1 co-receptor CCR5. Sequences covered the V3-loop of gp120, known to be the main determinant of co-receptor tropism. First, we evaluated this data with a computational model for the interpretation of V3-sequences with respect to tropism, and we found complete agreement with results from phenotypic assays. Thus, the method could be applied in cases where phenotypic assays fail. Second, computational analysis led to the discovery of a characteristic pattern in the quasi-species that foreshadows switches of co-receptor tropism. This analysis could help to unravel the mechanism of tropism switches, and to predict these switches weeks to months before they can be detected by a phenotypic assay.
Osteoprotective effects of Fructus Ligustri Lucidi aqueous extract in aged ovariectomized rats
Authors: Ko Chun Hay , Siu Wing Sum , Lau Ching Po , Lau ClaraBik San , Fung Kwok Pui , Leung Ping Chung
Published: November 2010

Background

Fructus Ligustri Lucidi (FLL) is a commonly used herb for treating bone disorders in Chinese medicine. The present study investigates the anti-osteoporotic activity of FLL aqueous extract in the model of postmenopausal bone loss in aged ovariectomized (OVX) female rats.

Methods

After eight weeks of treatment of FLL or water, the lumbar spine was scanned by peripheral quantitative computed tomography (pQCT). Effects of FLL water extract on osteogenic and adipogenic differentiations in rat mesenchymal stem cells (MSCs) were assessed by biochemical methods and staining.

Results

FLL aqueous extract significantly inhibited bone mineral density (BMD) loss in total, trabecular and cortical bones without affecting body weight and uterus wet weight. FLL extract significantly promoted osteogenesis and suppressed adipogenesis in MSCs as indicated by the elevated alkaline phosphatase activity, calcium deposition levels and decreased adipocyte number in a dose-dependent manner without cytotoxic effects. Real-time PCR analysis revealed significant increase of osteoprotegerin (OPG)-to-receptor activator for nuclear factor-κB ligand (RANKL) mRNA, indicating a decrease in osteoclastogenesis.

Conclusion

The present study demonstrates the osteoprotective effects of FLL aqueous extract on aged OVX rats, stimulation of osteogenesis, inhibition of adipogenesis and osteoclastogenesis in MSCs.
A simple technique to position patients with bilateral above-knee amputations for operative fixation of intertrochanteric fractures of the femur: a case report
Authors: Aqil Adeel , Desai Aravind , Dramis Asterios , Hossain Saqif
Published: November 2010

Introduction

Intertrochanteric fractures of the femur are common fractures in the elderly, and management includes operative fixation after patient positioning on the fracture table. Patients with bilateral above-knee amputations are challenging in terms of positioning on the table. We describe a simple technique to overcome this special problem.

Case presentation

A 75-year-old wheelchair-bound Caucasian man with bilateral above-knee amputations presented to our hospital after a fall. Plain radiographs showed an intertrochanteric fracture of the femur, and operative fixation with a dynamic hip screw was planned. His positioning on the table posed a particular problem, and therefore we developed a technique to overcome this problem.

Conclusion

Positioning of patients for fixation of intertrochanteric fractures of the femur poses a particular problem that can be solved by using our simple technique.
Vitamin D deficiency in rheumatoid arthritis: prevalence, determinants and associations with disease activity and disability
Authors: Rossini Maurizio , Maddali Bongi Susanna , La Montagna Giovanni , Minisola Giovanni , Malavolta Nazzarena , Bernini Luigi , Cacace Enrico , Sinigaglia Luigi , Di Munno Ombretta , Adami Silvano
Published: November 2010

Introduction

The aim of this study was to estimate the prevalence and determinants of vitamin D deficiency in patients with rheumatoid arthritis (RA) as compared to healthy controls and to analyze the association between 25-hydroxyvitamin D (25(OH)D) with disease activity and disability.

Methods

The study includes 1,191 consecutive RA patients (85% women) and 1,019 controls, not on vitamin D supplements, from 22 Italian rheumatology centres. Together with parameters of disease activity, functional impairment, and mean sun exposure time, all patients had serum 25(OH)D measured in a centralized laboratory.

Results

A total of 55% of RA patients were not taking vitamin D supplements; the proportion of these with vitamin D deficiency (25(OH)D level <20 ng/ml) was 52%. This proportion was similar to that observed in control subjects (58.7%). One third of supplemented patients were still vitamin D deficient. In non-supplemented RA patients 25(OH)D levels were negatively correlated with the Health Assessment Questionnaire Disability Index, Disease Activity Score (DAS28), and Mobility Activities of daily living score. Significantly lower 25(OH)D values were found in patients not in disease remission or responding poorly to treatment, and with the highest Steinbrocker functional state. Body mass index (BMI) and sun exposure time were good predictors of 25(OH)D values (P < 0.001). The association between disease activity or functional scores and 25(OH)D levels remained statistically significant even after adjusting 25(OH)D levels for both BMI and sun exposure time.

Conclusions

In RA patients vitamin D deficiency is quite common, but similar to that found in control subjects; disease activity and disability scores are inversely related to 25(OH)D levels.
PD-L1 blockade improves survival in experimental sepsis by inhibiting lymphocyte apoptosis and reversing monocyte dysfunction
Authors: Zhang Yan , Zhou Ying , Lou Jingsheng , Li Jinbao , Bo Lulong , Zhu Keming , Wan Xiaojian , Deng Xiaoming , Cai Zailong
Published: November 2010

Introduction

Lymphocyte apoptosis and monocyte dysfunction play a pivotal role in sepsis-induced immunosuppression. Programmed death-1 (PD1) and its ligand programmed death ligand-1 (PD-L1) exert inhibitory function by regulating the balance among T cell activation, tolerance, and immunopathology. PD-1 deficiency or blockade has been shown to improve survival in murine sepsis. However, PD-L1 and PD-1 differ in their expression patterns and the role of PD-L1 in sepsis-induced immunosuppression is still unknown.

Methods

Sepsis was induced in adult C57BL/6 male mice via cecal ligation and puncture (CLP). The expression of PD-1 and PD-L1 expression on peripheral T cells, B cells and monocytes were measured 24 hours after CLP or sham surgery. Additionally, the effects of anti-PD-L1 antibody on lymphocyte number, apoptosis of spleen and thymus, activities of caspase-8 and caspase-9, cytokine production, bacterial clearance, and survival were determined.

Results

Expression of PD-1 on T cells, B cells and monocytes and PD-L1 on B cells and monocytes were up-regulated in septic animals compared to sham-operated controls. PD-L1 blockade significantly improved survival of CLP mice. Anti-PD-L1 antibody administration prevented sepsis-induced depletion of lymphocytes, increased tumor necrosis factor (TNF)-α and interleukin (IL)-6 production, decreased IL-10 production, and enhanced bacterial clearance.

Conclusions

PD-L1 blockade exerts a protective effect on sepsis at least partly by inhibiting lymphocyte apoptosis and reversing monocyte dysfunction. Anti-PD-L1 antibody administration may be a promising therapeutic strategy for sepsis-induced immunosuppression.
Biot critical frequency applied to description of failure and yield of highly porous chalk with different pore fluids
Authors: Andreassen Katrine Alling , Fabricius Ida Lykke
Published: November 2010

Injection of water into chalk hydrocarbon reservoirs has led to mechanical yield and failure. Laboratory experiments on chalk samples correspondingly show that the mechanical properties of porous chalk depend on pore fluid and temperature. In case of water-saturated samples, the concentration and nature of dissolved salts have an effect. Water has a significant softening effect on elastic properties of chalk as calculated from wave data, and the softening increases with increasing critical frequency as defined by Biot. The critical frequency is the highest frequency where elastic wave propagation is controlled by solid-fluid friction. The reference frequency is thus a measure of this friction, and we propose that the fluid effect on mechanical properties of chalk may be the result of liquid-solid friction. We reviewed 622 published experiments on mechanical properties of porouschalk. The data include chalk samples that were tested at temperatures from [Formula: see text] with the following pore fluids: fresh water, synthetic seawater, glycol, and oil of varying viscosity. The critical frequency is calculated for each experiment. For each specimen, we calculate the thickness to the slipping plane outside the Stern layer on the pore surface. For electrolytes, the thickness of this layer is calculated based on Debye-Hückel theory. The layer reduces the porosity available for fluid flow. We find that the Biot critical frequency based on pore scale data can be used to explain effects on the macro scale. We find that the effective yield stress and also the effective stress of failure in tension as well as in compression are log-linearly related to log reference frequency. This opens the possibility to predict yield and failure under reservoir conditions from mechanical tests made under laboratory conditions. It also opens the possibility of predicting the effects of water flooding on chalk stability.
Treatment adherence in psychoses
Authors: David Anthony S.
Published: November 2010

A well-conducted randomised controlled trial of an intervention to improve treatment adherence in psychosis published in this issue shows beneficial effects on self- and observer-rated adherence and trends towards fewer hospital readmissions. Partial adherence is the single most important barrier to optimal treatment. National Institute for Health and Clinical Excellence guidelines on adherence need to be revised.
Fasting C-Peptide Levels and Death Resulting From All Causes and Breast Cancer: The Health, Eating, Activity, and Lifestyle Study
Authors: Irwin Melinda L. , Duggan Catherine , Wang Ching-Yun , Smith Ashley Wilder , McTiernan Anne , Baumgartner Richard N. , Baumgartner Kathy B. , Bernstein Leslie , Ballard-Barbash Rachel
Published: November 2010

Purpose

To examine the association between serum C-peptide, a marker of insulin secretion, measured 3 years after a breast cancer diagnosis, and death resulting from all causes and breast cancer.

Patients and Methods

This was a prospective, observational study of 604 women enrolled onto the Health, Eating, Activity, and Lifestyle (HEAL) Study who were diagnosed with local or regional breast cancer between 1995 and 1998 and observed until death or December 31, 2006, whichever came first. The hazard ratio (HR) for all deaths and deaths owing to breast cancer and 95% CIs for the HR were estimated using multivariable stratified Cox regression analyses.

Results

Among women without type 2 diabetes, fasting C-peptide levels were associated with an increased risk of death resulting from all causes and from breast cancer. A 1-ng/mL increase in C-peptide was associated with a 31% increased risk of any death (HR = 1.31; 95% CI, 1.06 to 1.63; P = .013) and a 35% increased risk of death as a result of breast cancer (HR = 1.35; 95% CI, 1.02 to 1.87, P = .048). Associations between C-peptide levels and death as a result of breast cancer were stronger in certain subgroups, including women with type 2 diabetes, women with a body mass index less than 25 kg/m2, women diagnosed with a higher stage of disease, and women whose tumors were estrogen receptor positive.

Conclusion

Treatment strategies to reduce C-peptide levels in patients with breast cancer, including dietary-induced weight loss, physical activity, and/or use of insulin-lowering medications, should be explored.
Improving Relative Survival, But Large Remaining Differences in Survival for Non-Hodgkin's Lymphoma Across Europe and the United States From 1990 to 2004
Authors: van de Schans Saskia A.M. , Gondos Adam , van Spronsen Dick Johan , Rachtan Jadwiga , Holleczek Bernd , Zanetti Roberto , Coebergh Jan Willem W. , Janssen-Heijnen Maryska L.G. , Brenner Hermann
Published: November 2010

Purpose

Non-Hodgkin's lymphoma (NHL) is the most common hematologic malignant neoplasm in adults. Monitoring differential changes in population-based survival is across Europe and the United States (US) could point to progress attained and impact of application of novel treatments.

Patients and Methods

We examined trends in age-specific 5-year relative survival among patients with NHL age 15 years or older between 1990 and 1994 and 2000 and 2004, on the basis of follow-up data from 12 population-based cancer registries across Europe, using period analysis techniques and compared the results with similar trends of patients with NHL in the US, as recorded in the Surveillance, Epidemiology, and End Results database.

Results

By 2000 to 2004, overall 5-year relative survival of patients with NHL across Europe was between 37% and 62%, achieved by overall increases in 5-year relative survival ranging from 4% to 12% units between 1990 and 1994 and 2000 and 2004. Changes in age-specific survival ranged from −1% to 43% units during the same time interval. For patients with NHL older than age 55 years, relative survival in individual European registries for the whole period was between 8% and 36% units lower than in the US, theoretically representing a lag of 4 to 10 years of progress.

Conclusion

Our analyses disclosed a strong and ongoing increase in long-term survival for patients with NHL in European populations. The geographic differences potentially indicate that further improvements could be possible, especially for patients age 55 years or older. The presumptive delay in improvement in survival among elderly patients with NHL in Europe remains to be clarified.
Clinically Defined Type 2 Diabetes Mellitus and Prognosis in Early-Stage Breast Cancer
Authors: Erickson Kirsten , Patterson Ruth E. , Flatt Shirley W. , Natarajan Loki , Parker Barbara A. , Heath Dennis D. , Laughlin Gail A. , Saquib Nazmus , Rock Cheryl L. , Pierce John P.
Published: November 2010

Purpose

Self-reported diabetes has been associated with poor breast cancer outcomes. Research is needed to investigate the relationship between biologically determined glycemic control and breast cancer prognosis.

Methods

Archived baseline blood samples from the Women's Healthy Eating and Living Study were used to measure hemoglobin A1C (HbA1C) among 3,003 survivors of early-stage breast cancer (age of diagnosis, 28 to 70 years) observed for a median of 7.3 years for additional breast cancer events and 10.3 years for all-cause mortality. HbA1C levels provide an accurate, precise measure of chronic glycemic levels. Cox regression analysis was performed to assess whether baseline HbA1C levels predicted disease-free and overall survival.

Results

Only 5.8% of women had chronic hyperglycemia (defined as HbA1C levels ≥ 6.5%). Those with HbA1C ≥ 6.5% were older and more likely to be less educated, have nonwhite ethnicity, be obese, and have more advanced breast cancer at diagnosis. HbA1C was significantly associated with overall survival (Ptrend < .001). After adjusting for confounders, risk of all-cause mortality was twice as high in women with HbA1C ≥ 7.0% compared with women with HbA1C less than 6.5% (hazard ratio [HR], 2.35; 95% CI, 1.56 to 3.54). For disease-free survival, there was a nonsignificant 30% increase in risk for HbA1C levels ≥ 7.0% (HR, 1.26; 95% CI, 0.78 to 2.02). During study follow-up, previously diagnosed rather than undiagnosed diabetes seemed to account for the increased risk.

Conclusion

Chronic hyperglycemia is statistically significantly associated with reduced overall survival in survivors of early-stage breast cancer. Further study of diabetes and its relationship to breast cancer outcomes is warranted.
Effect of Obesity on Prognosis After Early-Stage Breast Cancer
Authors: Ewertz Marianne , Jensen Maj-Britt , Gunnarsdóttir Katrín Á. , Højris Inger , Jakobsen Erik H. , Nielsen Dorte , Stenbygaard Lars E. , Tange Ulla B. , Cold Søren
Published: November 2010

Purpose

This study was performed to characterize the impact of obesity on the risk of breast cancer recurrence and death as a result of breast cancer or other causes in relation to adjuvant treatment.

Patients and Methods

Information on body mass index (BMI) at diagnosis was available for 18,967 (35%) of 53,816 women treated for early-stage breast cancer in Denmark between 1977 and 2006 with complete follow-up for first events (locoregional recurrences and distant metastases) up to 10 years and for death up to 30 years. Information was available on prognostic factors and adjuvant treatment for all patients. Univariate analyses were used to compare the associations of known prognostic factors and risks of recurrence or death according to BMI categories. Cox proportional hazards regression models were used to assess the influence of BMI after adjusting for other factors.

Results

Patients with a BMI of 30 kg/m2 or more were older and had more advanced disease at diagnosis compared with patients with a BMI below 25 kg/m2 (P < .001). When data were adjusted for disease characteristics, the risk of developing distant metastases after 10 years was significantly increased by 46%, and the risk of dying as a result of breast cancer after 30 years was significantly increased by 38% for patients with a BMI of 30 kg/m2 or more. BMI had no influence on the risk of locoregional recurrences. Both chemotherapy and endocrine therapy seemed to be less effective after 10 or more years for patients with BMIs greater than 30 kg/m2.

Conclusion

Obesity is an independent prognostic factor for developing distant metastases and for death as a result of breast cancer; the effects of adjuvant therapy seem to be lost more rapidly in patients with breast cancer and obesity.
Analysis of EPCAM Protein Expression in Diagnostics of Lynch Syndrome
Authors: Kloor Matthias , Voigt Anita Y. , Schackert Hans K. , Schirmacher Peter , von Knebel Doeberitz Magnus , Bläker Hendrik
Published: November 2010

Purpose

Lynch syndrome is an inherited tumor predisposition syndrome caused by germline mutations of DNA mismatch repair (MMR) genes, mainly MLH1 and MSH2. Recently, germline deletions affecting the epithelial cell adhesion molecule (EPCAM) gene located upstream of MSH2 were identified as a novel mutational mechanism causing Lynch syndrome by epigenetic inactivation of the respective MSH2 allele. Immunohistochemical analysis of MMR protein expression is a hallmark of Lynch syndrome diagnostics, but it cannot distinguish between EPCAM deletion carriers and MSH2 mutation carriers. We hypothesized that EPCAM protein expression might be altered in tumors from patients with a germline EPCAM deletion.

Patients and Methods

Immunohistochemistry was used to assess EPCAM expression in Lynch syndrome–associated MSH2-negative tumors (n = 26). Multiplex ligation-dependent probe amplification (MLPA) analysis was performed to detect germline deletions of the EPCAM and MSH2 gene loci.

Results

In four MSH2-negative tumors, a concomitant lack of EPCAM expression was detected. MLPA analysis revealed heterozygous EPCAM deletions in all patients with EPCAM-negative tumors. In contrast, EPCAM expression was positive in all cancers from patients with germline alterations affecting MSH2 but not EPCAM. Two EPCAM deletions were detected in patients with an EPCAM-positive tumor.

Conclusion

These results indicate that loss of EPCAM protein expression is frequent in tumors from patients with EPCAM germline deletions. EPCAM immunohistochemistry therefore represents a promising novel tool for the identification of Lynch syndrome patients with EPCAM germline deletions.
Regulation ofC. eleganspresynaptic differentiation and neurite branching via a novel signaling pathway initiated by SAM-10
Authors: Zheng Qun , Schaefer Anneliese M. , Nonet Michael L.
Published: November 2010

Little is known about transcriptional control of neurite branching or presynaptic differentiation, events that occur relatively late in neuronal development. Using the Caenorhabditis elegans mechanosensory circuit as an in vivo model, we show that SAM-10, an ortholog of mammalian single-stranded DNA-binding protein (SSDP), functions cell-autonomously in the nucleus to regulate synaptic differentiation, as well as positioning of, a single neurite branch. PLM mechanosensory neurons in sam-10 mutants exhibit abnormal placement of the neurite branch point, and defective synaptogenesis, characterized by an overextended synaptic varicosity, underdeveloped synaptic morphology and disrupted colocalization of active zone and synaptic vesicles. SAM-10 functions coordinately with Lim domain-binding protein 1 (LDB-1), demonstrated by our observations that: (1) mutations in either gene show similar defects in PLM neurons; and (2) LDB-1 is required for SAM-10 nuclear localization. SAM-10 regulates PLM synaptic differentiation by suppressing transcription of prk-2, which encodes an ortholog of the mammalian Pim kinase family. PRK-2-mediated activities of SAM-10 are specifically involved in PLM synaptic differentiation, but not other sam-10 phenotypes such as neurite branching. Thus, these data reveal a novel transcriptional signaling pathway that regulates neuronal specification of neurite branching and presynaptic differentiation.