bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational Fluid Dynamics (CFD) Modelling of Particle Deposition in a Two-dimensional Turbulent Channel Air Flow: Study of Influence Factors
Authors: Jiang Hai , Lu Lin , Sun Ke
Published: August 2011

This paper investigates the deposition of micro-particles in two-dimensional turbulent channel flows by using a developed computational fluid dynamics (CFD) model. The Reynolds stress model (RSM) and the Lagrangian particle tracking method were employed to predict the turbulent air flow and reveal the particle physical behaviours, respectively. The near wall fluctuating velocity was corrected with a damping function. Turbulent dispersion of the particles was taken into account by adopting the discrete random walk model. Deposition velocities of particles with the sizes from 1 to 50 µm were calculated. The simulation results agreed well with available experimental data and the accuracy of this model was evaluated. The influences of Saffman lift force, particle–wall boundary condition, particle density and gravity force on the particle deposition velocity were investigated respectively by using the developed model. The results of present work could be helpful in simulating particle-gas flow in industrial and environmental applications.
Friend or foe? Right-wing populism and the popular press in Britain and the Netherlands
Authors: Akkerman Tjitske
Published: August 2011

The popular press is supposed to display more sympathy for populist parties. This article investigates whether popular newspapers have a stronger tendency than serious newspapers to share the anti-establishment position of populist parties. It also tests the assumption that populist parties and the popular press share a tendency to personalize politics. The popular press in Britain and in the Netherlands are compared. The focus is on the Dutch Party for Freedom (PVV) and the Dutch newspaper the Telegraaf, and the British National Party (BNP) and The Sun. The analysis shows that the popular newspapers do not have an anti-elite bias. The Telegraaf and The Sun are overall even more oriented towards elitist perspectives than the quality press. The personalization thesis is not confirmed either. The results throw into doubt whether there is a single tabloid-quality spectrum based on subject matter or political orientation: subject matter and political orientation should not be conflated with differences in style.
Activist research and city politics: Ethical lessons from youth-based public scholarship
Authors: Carr John
Published: August 2011

This article offers observations from an ongoing action research project involving advocacy for public skateboarding facilities in Seattle, Washington to demonstrate both the need for, and the inherent limits to an ethical framework for action rooted in the Kantian moral imperative of treating all people as ‘ends and not means'. By tracing the ethical dilemmas arising from work seeking to advocate on behalf of young people through conventional urban politics, I argue that a ‘covenantal’ ethic should be extended not only to the action researcher's research community, but also to those with whom we compete in the political arena. In support of this argument, Idescribe both the ethical problems arising from purporting to speak on behalf young people, and the difficulties in ethically seeking policy change through urban politics and planning – particularly given the tendencies for political debate to revolve around essentialized constructions of youth identities, and for urban planning processes to reinforce neighborhood level disparities in power.
Exploring the Contribution of Virtual Worlds to Learning in Organizations
Authors: Li Jessica , D'Souza Derrick , Yunfei Du
Published: August 2011

Despite the growing interest of business executives, there is limited academic research on the contributions of virtual worlds to learning in organizations. We address this limitation by using a recently developed typology of virtual world capabilities to investigate the potential contributions of virtual worlds to learning in organizations. Recognizing that learning occurs at three levels within the organization, we proceed to develop a theoretical framework that relates virtual world capabilities to learning at each level. Our research contributes to the field by integrating multiple theoretically anchored dimensions and offering a framework that should serve as a building block for research on, and use of, virtual worlds in learning interventions in organizational settings.
Long-term effects of a community-based lifestyle intervention to prevent type 2 diabetes: the DEPLOY extension pilot study
Authors: Ackermann Ronald T , Finch Emily A , Caffrey Helena M , Lipscomb Elaine R , Hays Laura M , Saha Chandan
Published: August 2011

Objective: The US Diabetes Prevention Program (DPP) and other large trials internationally have shown that an intensive lifestyle intervention can reduce the development of type 2 diabetes. We evaluated long-term effects of a lower cost, group-based adaption of the DPP lifestyle intervention offered by the YMCA.

Methods: Participants were adults with BMI ≥24 kg/m2 and random capillary blood glucose 6.1–11.1 mmol/L who had been previously enrolled in a cluster-randomized trial comparing a group-based DPP lifestyle intervention versus brief advice alone. Four to 12 months after completion of the initial trial, 72% of 92 participants enrolled in an extension study, and all were offered a group lifestyle maintenance program at the YMCA. Paired t-tests were used to assess within-group changes; ANCOVA with adjustment was used for between-group comparisons.

Results: At 28 months, after both arms were offered the same 8-month lifestyle maintenance intervention, both arms had statistically significant weight losses compared to baseline (brief advice controls: −3.6%; 95% CI: −5.8 to −1.4; intensive lifestyle: −6.0%; 95% CI: −8.8 to −3.2). Participants initially assigned to the DPP also experienced significant improvements in blood pressure and total cholesterol.

Discussion: The YMCA is a promising channel for dissemination of a low-cost model for lifestyle diabetes prevention. Future studies are needed to verify these findings.
‘Monument to the international community, from the grateful citizens of Sarajevo’: Dark humour as counter-memory in post-conflict Bosnia-Herzegovina
Authors: Sheftel Anna
Published: August 2011

The challenges of remembering and memorializing the violence of Bosnia-Herzegovina’s tumultuous 20th century have captivated numerous scholars’ imaginations, because Bosnia is a remarkable example of both the utility and abuse of wartime memory. However, the elephant in the room during these discussions is the role of dark humour in narratives of Bosnia’s recent past. This article argues that dark humour is an especially subversive form of counter-memory, that allows Bosnians to express dissent from dominant narratives of the Bosnian War that they perceive as unproductive or divisive. Examples are drawn from oral histories, film and monuments to demonstrate how humour speaks to three major themes of Bosnian remembering: the idea of Bosnians as powerless victims; the seemingly arbitrary nature of the war and its aftermath; and the failures of the international community before, during and after the war. Bosnian dark humour critiques not only the above themes, but simultaneously the social structures in place for discussing the past.
The Attempt to Standardize Technical and Analytic Competence in Sonography Education
Authors: Baker Sara , Willey Bridgett , Mitchell Carol
Published: August 2011

The assessment of clinical, technical, and analytical competence can be a challenging task in sonography education. The assessment process is typically subjective, and because of this, it can be difficult to accurately evaluate students. This study researched the implementation of using an objective structured clinical examination (OSCE) for diagnostic medical sonography students. The examination consisted of two components: (1) image analysis and (2) scanning. This examination involved first- and second-year sonography students. The results indicated that an objective assessment of technical and analytic skills could play an integral role in the evaluation process for sonography education. The objectives of this study were to determine (1) the reliability of the OSCE to test sonography students, (2) the validity of the OSCE in measuring the performance of sonography students at different levels in their education, and (3) the usefulness of the information received from this test.
Normal Transvaginal Sonography Endometrial Thickness Measurements Associated With Endometrial Cancer in the Symptomatic Postmenopausal Patient
Authors: Riggs Kathy A.
Published: August 2011

Carcinoma of the endometrium is a difficult abnormality to diagnose with sonography alone. In this case, a transvaginal sonogram resulted in unremarkable findings to evaluate a postmenopausal patient with vaginal bleeding. Further testing went on to establish a diagnosis of grade 1 endometroid adenocarcinoma.
Lysyl oxidase-like protein-2 regulates sprouting angiogenesis and type IV collagen assembly in the endothelial basement membrane
Authors: Bignon Marine , Pichol-Thievend Cathy , Hardouin Julie , Malbouyres Marilyne , Bréchot Nicolas , Nasciutti Luiz , Barret Alain , Teillon Jérémie , Guillon Emilie , Etienne Eric , Caron Michel , Joubert-Caron Raymonde , Monnot Catherine , Ruggiero Florence , Muller Laurent , Germain Stéphane
Published: August 2011

Sprouting angiogenesis is associated with extensive extracellular matrix (ECM) remodeling. The molecular mechanisms involved in building the vascular microenvironment and its impact on capillary formation remain elusive. We therefore performed a proteomic analysis of ECM from endothelial cells maintained in hypoxia, a major stimulator of angiogenesis. Here, we report the characterization of lysyl oxidase-like protein-2 (LOXL2) as a hypoxia-target expressed in neovessels and accumulated in the endothelial ECM. LOXL2 belongs to the lysyl oxidase family of secreted enzymes involved in ECM crosslinking. Knockdown experiments in Tg(fli1:egfp)y1 zebrafish embryos resulted in lack of intersegmental vessel circulation and demonstrated LOXL2 involvement in proper capillary formation. Further investigation in vitro by loss and gain of function experiments confirmed that LOXL2 was required for tubulogenesis in 3D fibrin gels and demonstrated that this enzyme was required for collagen IV assembly in the ECM. In addition, LOXL2 depletion down-regulated cell migration and proliferation. These data suggest a major role for LOXL2 in the organization of endothelial basal lamina and in the downstream mechanotransductive signaling. Altogether, our study provides the first evidence for the role of LOXL2 in regulating angiogenesis through collagen IV scaffolding.
ABT-737 is highly effective against molecular subgroups of multiple myeloma
Authors: Bodet Linda , Gomez-Bougie Patricia , Touzeau Cyrille , Dousset Christelle , Descamps Géraldine , Maïga Sophie , Avet-Loiseau Hervé , Bataille Régis , Moreau Philippe , Le Gouill Steven , Pellat-Deceunynck Catherine , Amiot Martine
Published: August 2011

Multiple myeloma is a plasma cell malignancy that is heterogeneous with respect to its causative molecular abnormalities and the treatment response of patients. The Bcl-2 protein family is critical for myeloma cell survival. ABT-737 is a cell-permeant compound that binds to Bcl-2 and Bcl-xL but not to Mcl-1. Using a myeloma cell line collection (n = 25) representative of different molecular translocations, we showed that ABT-737 effectively kills a subset of cell lines (n = 6), with a median lethal dose ranging from 7 ± 0.4nM to 150 ± 7.5nM. Of interest, all sensitive cell lines harbored a t(11;14). We demonstrated that ABT-737–sensitive and ABT-737–resistant cell lines could be differentiated by the BCL2/MCL1 expression ratio. A screen of a public expression database of myeloma patients indicates that the BCL2/MCL1 ratio of t(11;14) and hyperdiploid patients was significantly higher than in all other groups (P < .001). ABT-737 first induced the disruption of Bcl-2/Bax, Bcl-2/Bik, or Bcl-2/Puma complexes, followed by the disruption of Bcl-2 heterodimers with Bak and Bim. Altogether, the identification of a subset of cell lines and primary cells effectively killed by ABT-737 alone supported the evaluation of ABT-263, an orally active counterpart to ABT-737, for the treatment of t(11;14) and hyperdiploid groups of myeloma harboring a Bcl-2high/Mcl-1low profile.
Clofarabine and busulfan conditioning facilitates engraftment and provides significant antitumor activity in nonremission hematologic malignancies
Authors: Magenau John , Tobai Hiromi , Pawarode Attaphol , Braun Thomas , Peres Edward , Reddy Pavan , Kitko Carrie , Choi Sung , Yanik Gregory , Frame David , Harris Andrew , Erba Harry , Kujawski Lisa , Elenitoba-Johnson Kojo , Sanks Jennifer , Jones Dawn , Paczesny Sophie , Ferrara James , Levine John , Mineishi Shin
Published: August 2011

Patients with hematologic malignancies not in remission before allogeneic hematopoietic stem cell transplantation (HSCT) have a poor prognosis. To improve the antitumor activity of conditioning, we combined clofarabine with myeloablative doses of busulfan in a phase 1/2 study in nonremission hematologic malignancies. Forty-six patients were enrolled, including 31 patients with nonremission acute myelogenous leukemia (AML). Patients had a median age of 53 years, with a median comorbidity index of 3. Donors were unrelated, HLA mismatched, or both in 59% of patients. Common grade III to IV nonhematologic toxicities included transient transaminitis (50%), mucositis (24%), hand-foot syndrome (13%), transient hypoxia (13%), nausea/vomiting (9%), and diarrhea (9%). All patients engrafted. Complete remission was achieved in 80% of all patients by day +30 and in 100% of AML patients without prior hematopoietic stem cell transplantation. Two-year nonrelapse mortality for all patients was 31%, and overall survival was 28%. In AML, the overall survival was 48% at 1 year and 35% at 2 years. These data suggest that clofarabine combined with myeloablative doses of busulfan is well tolerated, secures engraftment, and possesses significant antitumor activity, particularly in nonremission AML. This study is registered at www.ClinicalTrials.gov under identifier NCT00556452.
Withdrawal of inhaled corticosteroids in individuals with COPD - a systematic review and comment on trial methodology
Authors: Nadeem Nighat J , Taylor Stephanie JC , Eldridge Sandra M
Published: August 2011

Inhaled corticosteroids (ICS) reduce COPD exacerbation frequency and slow decline in health related quality of life but have little effect on lung function, do not reduce mortality, and increase the risk of pneumonia. We systematically reviewed trials in which ICS have been withdrawn from patients with COPD, with the aim of determining the effect of withdrawal, understanding the differing results between trials, and making recommendations for improving methodology in future trials where medication is withdrawn. Trials were identified by two independent reviewers using MEDLINE, EMBASE and CINAHL, citations of identified studies were checked, and experts contacted to identify further studies. Data extraction was completed independently by two reviewers. The methodological quality of each trial was determined by assessing possible sources of systematic bias as recommended by the Cochrane collaboration. We included four trials; the quality of three was adequate. In all trials, outcomes were generally worse for patients who had had ICS withdrawn, but differences between outcomes for these patients and patients who continued with medication were mostly small and not statistically significant. Due to data paucity we performed only one meta-analysis; this indicated that patients who had had medication withdrawn were 1.11 (95% CI 0.84 to 1.46) times more likely to have an exacerbation in the following year, but the definition of exacerbations was not consistent between the three trials, and the impact of withdrawal was smaller in recent trials which were also trials conducted under conditions that reflected routine practice. There is no evidence from this review that withdrawing ICS in routine practice results in important deterioration in patient outcomes. Furthermore, the extent of increase in exacerbations depends on the way exacerbations are defined and managed and may depend on the use of other medication. In trials where medication is withdrawn, investigators should report other medication use, definitions of exacerbations and management of patients clearly. Intention to treat analyses should be used and interpreted appropriately.
IQMNMR: Open source software using time-domain NMR data for automated identification and quantification of metabolites in batches
Authors: Song Xu , Zhang Bo-Li , Liu Hong-Min , Yu Bo-Yang , Gao Xiu-Mei , Kang Li-Yuan
Published: August 2011

Background

One of the most promising aspects of metabolomics is metabolic modeling and simulation. Central to such applications is automated high-throughput identification and quantification of metabolites. NMR spectroscopy is a reproducible, nondestructive, and nonselective method that has served as the foundation of metabolomics studies. However, the automated high-throughput identification and quantification of metabolites in NMR spectroscopy is limited by severe spectral overlap. Although numerous software programs have been developed for resolving overlapping resonances, as well as for identifying and quantifying metabolites, most of these programs are frequency-domain methods, considerably influenced by phase shifts and baseline distortions, and effective only in small-scale studies. Almost all these programs require multiple spectra for each application, and do not automatically identify and quantify metabolites in batches.

Results

We created IQMNMR, an R package that integrates a relaxation algorithm, digital filter, and similarity search algorithm. It differs from existing software in that it is a time-domain method; it uses not only frequency to resolve overlapping resonances but also relaxation time constants; it requires only one NMR spectrum per application; is uninfluenced by phase shifts and baseline distortions; and most important, yields a batch of quantified metabolites.

Conclusions

IQMNMR provides a solution that can automatically identify and quantify metabolites by one-dimensional proton NMR spectroscopy. Its time-domain nature, stability against phase shifts and baseline distortions, requirement for only one NMR spectrum, and capability to output a batch of quantified metabolites are of considerable significance to metabolic modeling and simulation.

IQMNMR is available at http://cran.r-project.org/web/packages/IQMNMR/.
Physiologic cold shock of Moraxella catarrhalisaffects the expression of genes involved in the iron acquisition, serum resistance and immune evasion
Authors: Spaniol Violeta , Troller Rolf , Schaller André , Aebi Christoph
Published: August 2011

Background

Moraxella catarrhalis, a major nasopharyngeal pathogen of the human respiratory tract, is exposed to rapid downshifts of environmental temperature when humans breathe cold air. It was previously shown that the prevalence of pharyngeal colonization and respiratory tract infections caused by M. catarrhalis are greatest in winter. The aim of this study was to investigate how M. catarrhalis uses the physiologic exposure to cold air to upregulate pivotal survival systems in the pharynx that may contribute to M. catarrhalis virulence.

Results

A 26°C cold shock induces the expression of genes involved in transferrin and lactoferrin acquisition, and enhances binding of these proteins on the surface of M. catarrhalis. Exposure of M. catarrhalis to 26°C upregulates the expression of UspA2, a major outer membrane protein involved in serum resistance, leading to improved binding of vitronectin which neutralizes the lethal effect of human complement. In contrast, cold shock decreases the expression of Hemagglutinin, a major adhesin, which mediates B cell response, and reduces immunoglobulin D-binding on the surface of M. catarrhalis.

Conclusion

Cold shock of M. catarrhalis induces the expression of genes involved in iron acquisition, serum resistance and immune evasion. Thus, cold shock at a physiologically relevant temperature of 26°C induces in M. catarrhalis a complex of adaptive mechanisms that enables the bacterium to target their host cellular receptors or soluble effectors and may contribute to enhanced growth, colonization and virulence.
Association between polymorphisms in the coagulation factor VII gene and coronary heart disease risk in different ethnicities: a meta-analysis
Authors: Mo Xingbo , Hao Yongchen , Yang Xueli , Chen Shufeng , Lu Xiangfeng , Gu Dongfeng
Published: August 2011

Background

Previous studies have examined the association between polymorphisms in the coagulation factor VII gene and the risk of coronary heart disease (CHD), but those studies have been inconclusive. This study was conducted to assess the associations between these polymorphisms and CHD and evaluated the associations in different ethnicities.

Methods

Literature-based searching was conducted to collect data and two methods, namely fixed-effects and random-effects, were performed to pool the odds ratio (OR), together with the 95% confidence interval (CI). Publication bias and between-study heterogeneity were also examined.

Results

Thirty-nine case-control studies of the three polymorphisms, R353Q (rs6046), HVR4 and -323Ins10 (rs36208070) in factor VII gene and CHD were enrolled in this meta-analysis, including 9,151 cases of CHD and 14,099 controls for R353Q, 2,863 cases and 2,727 controls for HVR4, and 2,862 cases and 4,240 controls for -323Ins10. Significant association was only found in Asian population for R353Q (Q vs R), with pooled OR of 0.70(95%CI: 0.55, 0.90). For the -323Ins10 polymorphism (10 vs 0), we found significant associations in both Asian and European populations, with pooled ORs of 0.74(95%CI: 0.61, 0.88) and 0.63(95%CI: 0.53, 0.74), respectively. Marginal significant association was found between HVR4 (H7 vs H5+H6) and CHD (OR = 0.88, 95% CI: 0.78, 1.00). There was no evidence of publication bias, but between-study heterogeneity was found in the analyses.

Conclusions

The -323Ins10 polymorphism in factor VII gene is significantly associated with CHD in both Asian and European populations, while R353Q polymorphism showed trend for association with CHD in Asians. Lack of association was found for HVR4 polymorphism. Further studies are needed to confirm the association, especially for -323Ins10 polymorphism.
The first report of RPSA polymorphisms, also called 37/67 kDa LRP/LR gene, in sporadic Creutzfeldt-Jakob disease (CJD)
Authors: Yun Jisuk , Jin Hyoung-Tae , Lee Yun-Jung , Choi Eun-Kyoung , Carp Richard I , Jeong Byung-Hoon , Kim Yong-Sun
Published: August 2011

Background

Although polymorphisms of PRNP, the gene encoding prion protein, are known as a determinant affecting prion disease susceptibility, other genes also influence prion incubation time. This finding offers the opportunity to identify other genetic or environmental factor (s) modulating susceptibility to prion disease. Ribosomal protein SA (RPSA), also called 37 kDa laminin receptor precursor (LRP)/67 kDa laminin receptor (LR), acts as a receptor for laminin, viruses and prion proteins. The binding/internalization of prion protein is dependent for LRP/LR.

Methods

To identify other susceptibility genes involved in prion disease, we performed genetic analysis of RPSA. For this case-control study, we included 180 sporadic Creutzfeldt-Jakob disease (CJD) patients and 189 healthy Koreans. We investigated genotype and allele frequencies of polymorphism on RPSA by direct sequencing or restriction fragment length polymorphism (RFLP) analysis.

Results

We observed four single nucleotide polymorphisms (SNPs), including -8T>C (rs1803893) in the 5'-untranslated region (UTR) of exon 2, 134-32C>T (rs3772138) in the intron, 519G>A (rs2269350) in the intron and 793+58C>T (rs2723) in the intron on the RPSA. The 519G>A (at codon 173) is located in the direct PrP binding site. The genotypes and allele frequencies of the RPSA polymorphisms showed no significant differences between the controls and sporadic CJD patients.

Conclusion

These results suggest that these RPSA polymorphisms have no direct influence on the susceptibility to sporadic CJD. This was the first genetic association study of the polymorphisms of RPSA gene with sporadic CJD.
Potential dermal wound healing agent in Blechnum orientale Linn
Authors: Lai How Yee , Lim Yau Yan , Kim Kah Hwi
Published: August 2011

Background

Blechnum orientale Linn. (Blechnaceae) is used ethnomedicinally to treat wounds, boils, blisters or abscesses and sores, stomach pain and urinary bladder complaints. The aim of the study was to validate the ethnotherapeutic claim and to evaluate the effects of B. orientale water extract on wound healing activity.

Methods

Water extract of B. orientale was used. Excision wound healing activity was examined on Sprague-Dawley rats, dressed with 1% and 2% of the water extract. Control groups were dressed with the base cream (vehicle group, negative control) and 10% povidone-iodine (positive control) respectively. Healing was assessed based on contraction of wound size, mean epithelisation time, hydroxyproline content and histopathological examinations. Statistical analyses were performed using one way ANOVA followed by Tukey HSD test.

Results

Wound healing study revealed significant reduction in wound size and mean epithelisation time, and higher collagen synthesis in the 2% extract-treated group compared to the vehicle group. These findings were supported by histolopathological examinations of healed wound sections which showed greater tissue regeneration, more fibroblasts and angiogenesis in the 2% extract-treated group.

Conclusions

The ethnotherapeutic use of this fern is validated. The water extract of B. orientale is a potential candidate for the treatment of dermal wounds. Synergistic effects of both strong antioxidant and antibacterial activities in the extract are deduced to have accelerated the wound repair at the proliferative phase of the healing process.
A role for DNA-dependent activator of interferon regulatory factor in the recognition of herpes simplex virus type 1 by glial cells
Authors: Furr Samantha R , Chauhan Vinita S , Moerdyk-Schauwecker Megan J , Marriott Ian
Published: August 2011

Background

The rapid onset of potentially lethal neuroinflammation is a defining feature of viral encephalitis. Microglia and astrocytes are likely to play a significant role in viral encephalitis pathophysiology as they are ideally positioned to respond to invading central nervous system (CNS) pathogens by producing key inflammatory mediators. Recently, DNA-dependent activator of IFN regulatory factor (DAI) has been reported to function as an intracellular sensor for DNA viruses. To date, the expression and functional role of DAI in the inflammatory responses of resident CNS cells to neurotropic DNA viruses has not been reported.

Methods

Expression of DAI and its downstream effector molecules was determined in C57BL/6-derived microglia and astrocytes, either at rest or following exposure to herpes simplex virus type 1 (HSV-1) and/or murine gammaherpesvirus-68 (MHV-68), by immunoblot analysis. In addition, such expression was studied in ex vivo microglia/macrophages and astrocytes from uninfected animals or mice infected with HSV-1. Inflammatory cytokine production by glial cultures following transfection with a DAI specific ligand (B-DNA), or following HSV-1 challenge in the absence or presence of siRNA directed against DAI, was assessed by specific capture ELISA. The production of soluble neurotoxic mediators by HSV-1 infected glia following DAI knockdown was assessed by analysis of the susceptibility of neuron-like cells to conditioned glial media.

Results

We show that isolated microglia and astrocytes constitutively express DAI and its effector molecules, and show that such expression is upregulated following DNA virus challenge. We demonstrate that these resident CNS cells express DAIin situ, and show that its expression is similarly elevated in a murine model of HSV-1 encephalitis. Importantly, we show B-DNA transfection can elicit inflammatory cytokine production by isolated glial cells and DAI knockdown can significantly reduce microglial and astrocyte responses to HSV-1. Finally, we demonstrate that HSV-1 challenged microglia and astrocytes release neurotoxic mediators and show that such production is significantly attenuated following DAI knockdown.

Conclusions

The functional expression of DAI by microglia and astrocytes may represent an important innate immune mechanism underlying the rapid and potentially lethal inflammation associated with neurotropic DNA virus infection.
Effect of selenium supplementation on CD4 T-cell recovery, viral suppression, morbidity and quality of life of HIV-infected patients in Rwanda: study protocol for a randomized controlled trial
Authors: Kamwesiga Julius , Mutabazi Vincent , Kayumba Josephine , Tayari Jean-Claude K , Smyth Richard , Fay Heather , Umurerwa Alice , Baziruwiha Marcel , Ntizimira Christian , Murebwayire Antoinette , Haguma Jean Pierre , Nyiransabimana Julienne , Habarurema Donatille , Mukarukundo Veneranda , Nzabandora Jean Bosco , Nzamwita Pascal , Mukazayire Ernestine , Mills Edward J , Seely Dugald , McCready Douglas J , Warren Don
Published: August 2011

Background

Low levels of serum selenium are associated with increased risk of mortality among HIV+ patients in East Africa. We aim to assess the effect of selenium supplementation on CD4 cell count, HIV viral load, opportunistic infections, and quality of life in HIV-infected patients in Rwanda.

Methods and Design

A 24-month, multi-centre, patient and provider-blinded, randomized, placebo-controlled clinical trial involving 300 pre-antiretroviral therapy (ART) HIV-infected patients will be carried out at two sites in Rwanda. Patients ≥ 21 years of age with documented HIV infection, CD4 cell count of 400-650 cells/mm3, and not yet on ART will be recruited. Patients will be randomized at each study site using a randomized block design to receive either the selenium micronutrient supplement or an identically appearing placebo taken once daily. The primary outcome is a composite of time from baseline to reduction of CD4 T lymphocyte count below 350 cells/mm3 (confirmed by two measures at least one week apart), or start of ART, or the emergence of a documented CDC-defined AIDS-defining illness. An intention-to-treat analysis will be conducted using stepwise regression and structural equation modeling.

Discussion

Micronutrient interventions that aim to improve CD4 cell count, decrease opportunistic infections, decrease HIV viral load, and ultimately delay initiation of more costly ART may be beneficial, particularly in resource-constrained settings, such as sub-Saharan Africa. Additional trials are needed to determine if micro-supplementation can delay the need for more costly ART among HIV-infected patients. If shown to be effective, selenium supplementation may be of public health importance to HIV-infected populations, particularly in sub-Saharan Africa and other resource-constrained settings.

Trial Registration

NCT01327755
Examination of the bovine leukocyte environment using immunogenetic biomarkers to assess immunocompetence following exposure to weaning stress
Authors: O'Loughlin Aran , McGee Mark , Waters Sinéad M , Doyle Sean , Earley Bernadette
Published: August 2011

Background

The molecular mechanisms by which stress induces the development of pathologies remains unclear, although it is recognised that one of the major factors affecting health as a consequence of stress is the involvement of the neuroendocrine system. In cattle, a number of necessary husbandry practices have been shown to activate the stress response, yet very little is known about the impact these have at the molecular level. The objectives of the study were to characterise, in male and female beef calves, the immune response to weaning stress in bovine leukocytes at the physiological and molecular levels and to assess the difference between calves weaned in the presence of the dam and those weaned and penned away from the dam.

Results

Following exposure to weaning stress, total neutrophil number and neutrophil:lymphocyte (N:L) ratio increased (P < 0.01) in calves. Additionally, expression of pro-inflammatory cytokine genes, including IL-1β, IL-8, IFN-γ and TNFα, were up-regulated (P < 0.01). Furthermore, there was increased (P < 0.001) expression of the glucocorticoid receptor, GRα, the pro-apoptotic gene, Fas and the Gram-negative pattern recognition receptor, TLR4. Calves penned away from the dam post-weaning had increased (P < 0.01) neutrophil number and N:L ratio compared with calves penned next to the dam, and female calves had higher (P < 0.05) expression levels of IL-2, IL-8, IFN-γ and TNFα than male calves.

Conclusions

Weaning elicits an immediate and somewhat short-lived acute stress response in the calf. The effects serve to enhance, rather than suppress, the immune response by means of a heightened inflammatory response and cellular mobilization. The earlier and more profound increase in neutrophil number and N:L ratio together with reduced lymphocyte number in calves penned away compared with calves penned near their dams post-weaning suggests that the former may be more sensitive to weaning stress. The data also show a clear effect of gender in differential gene expression in response to stress with IFN-γ having increased expression in female calves compared with male calves over the course of the study. Additionally, this study has helped to characterise the inflammatory response to stress in calves and identify a number of novel candidate biomarkers suitable for investigation in future studies of stress.
Treatment of severe neutropenia with high-dose pyridoxine in a patient with chronic graft versus host disease and squamous cell carcinoma: a case report
Authors: Rauf Mariam , Gleason Charise , Nooka Ajay K , Husman Abbie , Waller Edmund K
Published: August 2011

Introduction

The differential diagnosis of neutropenia includes medications, infections, autoimmune diseases, and deficiencies of Vitamin B12 and folate. The association of Vitamin B6 deficiency with severe neutropenia is a rare finding.

Case presentation

A 51-year-old Caucasian woman presented with fever and profound neutropenia (48 neutrophils/uL). Her clinical history included non-Hodgkin lymphoma, in remission following treatment with allogeneic bone marrow transplantation, quiescent chronic graft-versus-host disease, and squamous cell carcinoma of the skin metastatic to cervical lymph nodes. Medications included atenolol, topical clobetasol, Ditropan (oxybutynin), prophylactic voriconazole, prophylactic valganciclovir, Soriatane (acitretin), and Carac (fluorouracil) cream. The bone marrow was hypocellular without metastatic cancer or myelodysplasia. Neutropenia did not respond to stopping medications that have been associated with neutropenia (valganciclovir, voriconazole and Soriatane) or treatment with antibiotics or granulocyte colony stimulating factor. Blood tests revealed absence of antineutrophil antibodies, normal folate and B12 levels, moderate zinc deficiency and severe Vitamin B6 deficiency. Replacement therapy with oral Vitamin B6 restored blood vitamin levels to the normal range and corrected the neutropenia. Her cervical adenopathy regressed clinically and became negative on scintography following Vitamin B6 therapy and normalization of the blood neutrophil count.

Conclusion

Severe pyridoxine deficiency can lead to neutropenia. Screening for Vitamin B6 deficiency, along with folate and Vitamin B12 levels, is recommended in patients with refractory neutropenia, especially those with possible malabsorption syndromes, or a history of chronic-graft-versus host disease. Severe neutropenia may facilitate progression of squamous cell carcinoma.
First detection of Leishmania killicki (Kinetoplastida, Trypanosomatidae) in Ctenodactylus gundi (Rodentia, Ctenodactylidae), a possible reservoir of human cutaneous leishmaniasis in Tunisia
Authors: Jaouadi Kaouther , Haouas Najoua , Chaara Dhekra , Gorcii Mohamed , Chargui Najla , Augot Denis , Pratlong Francine , Dedet Jean-Pierre , Ettlijani Selim , Mezhoud Habib , Babba Hamouda
Published: August 2011

Background

Leishmania killicki was originally described in 1980 in southeast Tunisia. It was also recently reported in Lybia and Algeria. Nevertheless, neither vector nor reservoirs of this parasite are known. The identification of the vector and the animal reservoir host of L. killicki is critical for the establishment of an efficient control strategy.

Findings

blood, popliteal lymph node, spleen, bone marrow, liver and skin were collected from 50 rodents in 2009 in south western Tunisia. Samples were smeared onto glass slides, cultured on NNN medium and tested by polymerase chain reaction for Leishmania detection. Parasites were detected by PCR from 10 Psammomys obesus and from two Ctenodactylus gundi. Parasite identification was performed simultaneously by internal transcribed spacer 1 PCR-RFLP and by PCR sequencing. Both Leishmania major and Leishmania killicki were identified from infected Psammomys and Ctenodactylus gundi respectively.

Conclusion

This is the first report of Leishmania killicki identified from Ctenodactylus gundi in Tunisia. This result supports the assumption that C. gundi is a potential reservoir for Leishmania killicki.
Allergic rhinitis in northern vietnam: increased risk of urban living according to a large population survey
Authors: Lâm Hoàng Thị , Văn Tường Nguyễn , Ekerljung Linda , Rönmark Eva , Lundbäck Bo
Published: August 2011

Background

Little is known about prevalence and risk factors of allergic rhinitis and chronic nasal symptoms among adults in Vietnam. We aimed to estimate the prevalence, risk factor patterns and co‐morbidities of allergic rhinitis and chronic nasal symptoms in one urban and one rural area in northern Vietnam.

Methods

A cross‐sectional questionnaire survey was conducted from August 2007 to January 2008 in urban Hoankiem and rural Bavi in Hanoi among adults aged 21‐70 years. Of 7008 randomly selected subjects, 91.7% participated in Bavi and 70.3% in Hoankiem.

Results

Allergic rhinitis ever or chronic nasal symptoms were reported by 50.2%. The prevalence of allergic rhinitis ever was considerably higher in Hoankiem compared to Bavi, 29.6% vs 10.0% (p < 0.001). Allergic rhinitis ever and chronic nasal symptoms were both significantly associated with asthma and respiratory symptoms, respectively (p < 0.001). Exposure to gas, dust or fumes at work was significantly associated with allergic rhinitis ever, OR 1.57 (95% CI 1.34 ‐ 1.84), nasal blocking, OR 1.90 (95% CI 1.68 ‐ 2.15) and runny nose, OR 1.32 (95% CI 1.17 ‐ 1.49), while somewhat surprisingly no association with smoking was found. Female sex was a significant risk factor for both nasal blocking and runny nose.

Conclusions

Allergic rhinitis ever was considerably more common in the urban area. Nasal blocking and runny nose was each reported by about one third of the studied sample with no major urban‐rural difference. Further, exposure to air pollution at work was significantly associated with allergic rhinitis ever, nasal blocking and runny nose.
Clinical detection and monitoring of acute pulmonary embolism: proof of concept of a computer-based method
Authors: Revie James A , Stevenson David J , Chase J Geoffrey , Hann Christopher E , Lambermont Bernard C , Ghuysen Alexandre , Kolh Philippe , Morimont Philippe , Shaw Geoffrey M , Desaive Thomas
Published: August 2011

Background

The diagnostic ability of computer-based methods for cardiovascular system (CVS) monitoring offers significant clinical potential. This research tests the clinical applicability of a newly improved computer-based method for the proof of concept case of tracking changes in important hemodynamic indices due to the influence acute pulmonary embolism (APE).

Methods

Hemodynamic measurements from a porcine model of APE were used to validate the method. Of these measurements, only those that are clinically available or inferable were used in to identify pig-specific computer models of the CVS, including the aortic and pulmonary artery pressure, stroke volume, heart rate, global end diastolic volume, and mitral and tricuspid valve closure times. Changes in the computer-derived parameters were analyzed and compared with experimental metrics and clinical indices to assess the clinical applicability of the technique and its ability to track the disease state.

Results

The subject-specific computer models accurately captured the increase in pulmonary resistance (R

pul
), the main cardiovascular consequence of APE, in all five pigs trials, which related well (R2 = 0.81) with the experimentally derived pulmonary vascular resistance. An increase in right ventricular contractility was identified, as expected, consistent with known reflex responses to APE. Furthermore, the modeled right ventricular expansion index (the ratio of right to left ventricular end diastolic volumes) closely followed the trends seen in the measured data (R2 = 0.92) used for validation, with sharp increases seen in the metric for the two pigs in a near-death state. These results show that the pig-specific models are capable of tracking disease-dependent changes in pulmonary resistance (afterload), right ventricular contractility (inotropy), and ventricular loading (preload) during induced APE. Continuous, accurate estimation of these fundamental metrics of cardiovascular status can help to assist clinicians with diagnosis, monitoring, and therapy-based decisions in an intensive care environment. Furthermore, because the method only uses measurements already available in the ICU, it can be implemented with no added risk to the patient and little extra cost.

Conclusions

This computer-based monitoring method shows potential for real-time, continuous diagnosis and monitoring of acute CVS dysfunction in critically ill patients.
TopHat-Fusion: an algorithm for discovery of novel fusion transcripts
Authors: Kim Daehwan , Salzberg Steven L
Published: August 2011

TopHat-Fusion is an algorithm designed to discover transcripts representing fusion gene products, which result from the breakage and re-joining of two different chromosomes, or from rearrangements within a chromosome. TopHat-Fusion is an enhanced version of TopHat, an efficient program that aligns RNA-seq reads without relying on existing annotation. Because it is independent of gene annotation, TopHat-Fusion can discover fusion products deriving from known genes, unknown genes and unannotated splice variants of known genes. Using RNA-seq data from breast and prostate cancer cell lines, we detected both previously reported and novel fusions with solid supporting evidence. TopHat-Fusion is available at http://tophat-fusion.sourceforge.net/.
APPL1 Mediates Adiponectin-Induced LKB1 Cytosolic Localization Through the PP2A-PKCζ Signaling Pathway
Authors: Deepa Sathyaseelan S. , Zhou Lijun , Ryu Jiyoon , Wang Changhua , Mao Xuming , Li Cai , Zhang Ning , Musi Nicolas , DeFronzo Ralph A. , Liu Feng , Dong Lily Q.
Published: August 2011

We recently found that the adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif (APPL)1 is essential for mediating adiponectin signal to induce liver kinase B (LKB)1 cytosloic translocation, an essential step for activation of AMP-activated protein kinase (AMPK) in cells. However, the underlying molecular mechanisms remain unknown. Here, we demonstrate that treating C2C12 myotubes with adiponectin promoted APPL1 interaction with protein phosphatase 2A (PP2A) and protein kinase Cζ (PKCζ), leading to the activation of PP2A and subsequent dephosphorylation and inactivation of PKCζ. The adiponectin-induced inactivation of PKCζ results in dephosphorylation of LKB1 at Ser307 and its subsequent translocation to the cytosol, where it stimulates AMPK activity. Interestingly, we found that metformin also induces LKB1 cytosolic translocation, but the stimulation is independent of APPL1 and the PP2A-PKCζ pathway. Together, our study uncovers a new mechanism underlying adiponectin-stimulated AMPK activation in muscle cells and shed light on potential targets for prevention and treatment of insulin resistance and its associated diseases.
Clinical and multidetector CT follow-up results of renal artery aneurysms treated by detachable coil embolization using 3D rotational angiography
Authors: Seo Jung Min , Park Kwang Bo , Kim Keon Ha , Jeon Pyoung , Shin Sung Wook , Park Hong Suk , Do Young Soo , Kim Dong-Ik , Kim Young-Wook
Published: August 2011

Background

There are very few reports regarding the use of 3D rotational angiography (3D RA) in embolization of renal artery aneurysms (RAAs). No valuable data have been reported on the follow-up result of coil embolization for RAAs on computed tomography (CT).

Purpose

To evaluate the clinical and multidetector computed tomography (MDCT) follow-up results of renal artery aneurysms treated by detachable coil embolization using 3D RA.

Material and Methods

Six patients diagnosed with RAAs were included. Five patients underwent detachable coil embolization. Five patients underwent 3D RA and the parameters used for planning endovascular treatment obtained by 2D CT, reformatted 3D CT angiography (3D CTA), 2D digital subtraction angiography (2D DSA) and 3D RA were compared. The postembolization MDCT follow-up findings were analyzed retrospectively.

Results

The technical success rate for detachable coil embolization was 40%. The 3D CTA showed the dome-to-neck ratio (DNR) and tangential view of the renal artery aneurysm in five patients (83.3%) and the 2D CT showed it in four (66.7%). An optimal working angle assessment could not be obtained on the 2D CT and 3D CTA. The 3D RA showed the DNR, tangential view, and optimal working angle in all patients. Renal infarction occurred in three patients and postprocedural hypertension developed in two patients during the follow-up period.

Conclusion

The 3D RA was useful in preoperative determination of adequate working angle for detachable coil embolization of RAAs. Late complications of detachable coil embolization for RAAs were renal infarction and hypertension.
Coronary CT angiography for acute chest pain triage: Techniques for radiation exposure reduction; 128 vs. 64 multidetector CT
Authors: Goitein Orly , Matetzky Shlomi , Eshet Yael , Goitein David , Hamdan Ashraf , Segni Elio Di , Konen Eli
Published: August 2011

Background

Coronary CT angiography (CCTA) is used daily in acute chest pain triage, although exposing patients to significant radiation dosage. CCTA using prospective ECG gating (PG CCTA) enables significant radiation reduction

Purpose

To determine whether the routine use of 128 vs. 64 multidetector CT (MDCT) can increase the proportion of patients scanned using PG CCTA technique, lowering radiation exposure, without decreasing image quality.

Material and Methods

The study comprised 232 patients, 116 consecutive patients scanned using 128 MDCT (mean age 49 years, 79 men, BMI 28) and 116 consecutive patients (mean age 50 years, 75 men, BMI 28) which were scanned using 64 MDCT. PG CCTA was performed whenever technically permissible by each type of scanner: 64 MDCT = stable heart rate (HR) <60/min and weight <110 kg; 128 MDCT = stable HR < 70/min and weight <140 kg. All coronary segments were evaluated for image quality using a visual scale of 1–5. An estimated radiation dose was recorded.

Results

PC CCTA was performed in 84% and 49% of the 128 and 64 MDCT groups, respectively ( P < 0.0001). Average image quality score were 4.6 ± 0.3 and 4.7 ± 0.1 for the 128 and 64 MDCT, respectively ( P = 0.08). The mean radiation dose exposure was 6.2 ± 4.8 mSv and 10.4 ± 7.5 mSv for the 128 and 64 MDCT, respectively ( P = 0.008).

Conclusion

The 128 MDCT scanner enables utilization of PG CCTA technique in a greater proportion of patients, thereby decreasing the related radiation significantly, without hampering image quality.