bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling Drug-Carrier Interaction in the Drug Release from Nanocarriers
Authors: Zeng Like , An Lingling , Wu Xiaoyi
Published: August 2011

Numerous nanocarriers of various compositions and geometries have been developed for the delivery and release of therapeutic and imaging agents. Due to the high specific surface areas of nanocarriers, different mechanisms such as ion pairing and hydrophobic interaction need to be explored for achieving sustained release. Recently, we developed a three-parameter model that considers reversible drug-carrier interaction and first-order drug release from liposomes. A closed-form analytical solution was obtained. Here, we further explore the ability of the model to capture the release of bioactive molecules such as drugs and growth factors from various nanocarriers. A parameter study demonstrates that the model is capable of resembling major categories of drug release kinetics. We further fit the model to 60 sets of experimental data from various drug release systems, including nanoparticles, hollow particles, fibers, and hollow fibers. Additionally, bootstrapping is used to evaluate the accuracy of parameter determination and validate the model in selected cases. The simplicity and universality of the model and the clear physical meanings of each model parameter render the model useful for the design and development of new drug delivery systems.
Changes of Photosynthetic Behaviors in Kappaphycus alvarezii Infected by Epiphyte
Authors: Pang Tong , Liu Jianguo , Liu Qian , Lin Wei
Published: August 2011

Epiphytic filamentous algae (EFA) were noted as a serious problem to reduce the production and quality of K. alvarezii. The morphological studies revealed that the main epiphyte on K. alvarezii was Neosiphonia savatieri in China. Though the harmful effects of EFA on the production of K. alvarezii have been reported, the detailed mechanism of the N. savatieri in limiting the production of K. alvarezii has not been studied yet. The present paper studied the effects of N. savatieri infection on photosynthetic behaviors in K. alvarezii by detecting chlorophyll fluorescence transient in vivo. The results revealed that damage of oxygen‐evolving complex (OEC), decrease of active reaction centers (RCs), and the plastoquinone (PQ) pool as well as significant reduction in the performance indexes (PI) of PSII were caused by the infection of N. savatieri. The influence of N. savatieri on photosynthetic activity of K. alvarezii should be one of the important reasons to reduce the production of K. alvarezii infected by N. savatieri.
Molecular Engineering of Nonplanar Porphyrin and Carbon Nanotube Assemblies: A Linear and Nonlinear Spectroscopic and Modeling Study
Authors: Ní Mhuircheartaigh Éimhín M. , Giordani Silvia , MacKernan Donal , King Sharon M. , Rickard David , Val Verde Lisa M. , Senge Mathias O. , Blau Werner J.
Published: August 2011

The importance of molecular conformation to the nature and strength of noncovalent interactions existing between a series of increasingly nonplanar tetraphenylporphyrin (TPP) derivatives and carbon nanotubes was systematically investigated experimentally in solution using a range of linear and nonlinear optical techniques. Additional complementary molecular dynamics studies were found to support the experimental observations. Convincing evidence of binding between single walled nanotubes (SWNTs) and some of these porphyrins was discovered, and a nonplanar macrocycle conformation was found to increase the likelihood of noncovalent binding onto nanotubes. Nonlinear optical studies showed that the optical limiting behavior of the TPP derivatives deteriorated with increasing porphyrin nonplanarity, but that formation of nanotube composites dramatically improved the optical limiting properties of all molecules studied. It was also found that the significant photoluminescence quenching behavior reported in the literature for such porphyrin/SWNT composites is at least partly caused by photoluminescence and excitation self-absorption and is, therefore, an artifact of the system.
Deviations in Circulating TNFαLevels and TNFαProduction by Mononuclear Cells in Healthy Human Populations
Authors: Mózes T. , Baráth I. , Gornicsar K. , Grosz A. , Mózes Ta. , Göndöcs Cs. , Széphalmi P. , Gaál K. , Madarász E.
Published: August 2011

Objectives. Tumor necrosis factor alpha (TNFα) plays a pivotal role in the inflammatory host response. The serum-level of TNFαand the production of TNFαby lympho/monocytes, however, seem to show high individual variations. The goal of the present study was to investigate the variations and inducibility of TNFα-activity in two age-groups of healthy volunteers.Methods. Sixty elderly, healthy volunteers were studied. These persons were free of malignant diseases, and within three months, they did not have any trauma or inflammatory disease and were not taking any steroids or nonsteroid anti-inflammatory drugs. Thirty young volunteers were also included. Blood samples were taken; lympho/monocytes were separated and cultured with or without endotoxin (LPS) stimulation. Serum and culture supernatant TNFαlevels were determined by bioassay using WEHI 164 cells.Results. The results indicated significant individual variations in TNFαlevels of healthy volunteers irrespective of age. Subgroups with low, middle, and high serum TNF-levels were distinguished. In about 50% of volunteers with low serum-TNFαactivity, LPS stimulation failed to increase the TNFαproduction by isolated lympho/monocytes.Conclusion. Our data suggest a chance to select individuals with enhanced sensitivity for septic complications.
Fighting psychiatric stigma in the classroom: The impact of an educational intervention on secondary school students’ attitudes to schizophrenia
Authors: Economou M. , Louki E. , Peppou L. E. , Gramandani C. , Yotis L. , Stefanis C. N.
Published: August 2011

Background:

Adolescents constitute an appealing target group for fighting stigma and discrimination surrounding mental illness, since it is during this developmental period that adult attitudes about mental illness are formed and consolidated.

Aim:

The aim of the present study was twofold, to explore adolescents’ beliefs and attitudes to schizophrenia and to evaluate the effectiveness of an anti-stigma intervention in altering them.

Methods:

A total of 616 high school students participated in the study, divided into a control condition and an anti-stigma intervention group. Data were collected at three time points: before the intervention, upon its completion and at a 12-month follow-up.

Results:

Baseline measurements indicated that students espoused certain stereotypical beliefs about patients with schizophrenia and were reluctant to interact with them on some occasions. Upon completion of the intervention, positive changes were recorded in students’ beliefs, attitudes and desired social distance; however, only the changes in beliefs and attitudes were maintained after one year.

Conclusion:

For anti-stigma interventions to be effective, they should be continuously delivered to students throughout the school years and allow for an interaction between students and patients. Health promotion programmes might be an appropriate context for incorporating such interventions.
Postnatal Neurogenesis
Authors: Walton R. M.
Published: August 2011

Over the past 20 years, the conception of brain development has radically changed from a fixed and limited hierarchical process to a more plastic and continuous one. Most surprising, the field has learned that postnatal neurogenesis is not just a seasonal phenomenon in songbirds but a process that occurs across species and seasons. Astrocytes, whose primary role in the central nervous system was thought to be strictly supportive, have emerged as a heterogeneous population, a subset of which is the neural stem cell. Postnatal neurogenesis persists in specialized niches within the rostral subventricular zone and hippocampal dentate gyrus and, for a limited period, within the white matter tracts and external granular layer of the cerebellum. These specialized microenvironments are influenced by factors in the blood, cerebrospinal fluid, and local extracellular matrix. This article reviews the current understanding of adult neurogenesis, which is conserved across many vertebrate species, underscoring the value of animal models in past and present studies of human neurogenesis and neurogenic disease.
Single-Legged Hop Tests as Predictors of Self-Reported Knee Function in Nonoperatively Treated Individuals With Anterior Cruciate Ligament Injury
Authors: Grindem Hege , Logerstedt David , Eitzen Ingrid , Moksnes Håvard , Axe Michael J. , Snyder-Mackler Lynn , Engebretsen Lars , Risberg May Arna
Published: August 2011

Background: Previous studies have found significant predictors for functional outcome after anterior cruciate ligament (ACL) reconstruction; however, studies examining predictors for functional outcome in nonoperatively treated individuals are lacking.

Hypothesis: Single-legged hop tests predict self-reported knee function (International Knee Documentation Committee [IKDC] 2000) in nonoperatively treated ACL-injured individuals 1 year after baseline testing.

Study Design: Cohort study (prognosis); Level of evidence, 2.

Methods: Ninety-one nonoperatively treated patients with an ACL injury were tested using 4 single-legged hop tests on average 74 ± 30 days after injury in a prospective cohort study. Eighty-one patients (89%) completed the IKDC 2000 1 year later. Patients with an IKDC 2000 score equal to or higher than the age- and gender-specific 15th percentile score from previously published data on an uninjured population were classified as having self-reported function within normal ranges. Logistic regression analyses were performed to identify predictors of self-reported knee function. The area under the curve (AUC) from receiver operating characteristic curves was used as a measure of discriminative accuracy. Optimal limb symmetry index (LSI) cutoff for the best single-legged hop test was defined as the LSI with the highest product of sensitivity and specificity.

Results: Single hop for distance symmetry indexes predicted self-reported knee function at the 1-year follow-up ( P = .036). Combinations of any 2 hop tests (AUC = 0.64-0.71) did not give a higher discriminative accuracy than the single hop alone (AUC = 0.71). A cutoff of 88% (LSI) for the single hop revealed a sensitivity of 71.4% and a specificity of 71.7%.

Conclusion: The single hop for distance (LSI) significantly predicted self-reported knee function after 1 year in nonoperatively treated ACL-injured patients. Combinations of 2 single-legged hop tests did not lead to higher discriminative accuracy than the single hop alone.
Prevalence and Correlates of Physical Spousal Violence Against Women in Slum and Nonslum Areas of Urban Bangladesh
Authors: Sambisa William , Angeles Gustavo , Lance Peter M. , Naved Ruchira T. , Thornton Juliana
Published: August 2011

This study explores the prevalence and correlates of past-year physical violence against women in slum and nonslum areas of urban Bangladesh. The authors use multivariate logistic regression to analyze data from the 2006 Urban Health Survey, a population-based survey of 9,122 currently married women aged between 15 and 49 who were selected using a multistage cluster sampling design. The prevalence of reported past-year physical spousal violence is 31%. Prevalence of past-year physical spousal violence is higher in slums (35%) than in nonslums (20%). Slapping/arm-twisting and pushing/shaking/ throwing something at the women are the most commonly reported acts of physical abuse. Multivariate analysis shows that the risk of physical spousal abuse is lower among older women, women with post—primary education, and those belonging to rich households and women whose husbands considered their opinion in decision making. Women are at higher risk of abuse if they had many children, believe that married woman should work if the husband is not making enough money, and approve wife-beating norms. This study serves to confirm the commonness of physical spousal abuse in urban Bangladesh, demonstrating the seriousness of this multifaceted phenomenon as a social and public health issue. The present findings suggest the need for comprehensive prevention and intervention strategies that capitalize on the interplay of individual and sociocultural factors that cause physical spousal violence. Our study adds to a growing literature documenting domestic violence against women in urban areas of developing south Asian nations.
Dialectical Practices in Education
Authors: Kozleski Elizabeth B.
Published: August 2011

In this commentary, the author provides a framework for examining the articles in this issue. The author does so by providing a focus for reading and linking our brief history to the present and the future. She provides a set of questions about engaging research that seeks to improve the ways in which we question, construct understanding, and interrogate one another in what counts in teacher education. For our field to mature and expand, we need spaces in which we can understand multiple perspectives, honor our differences, and find ways of improving how teachers learn and impact their students.
Theoretical investigation into the thermo-mechanical stresses in cross-ply laminated composite cylinder with finite length
Authors: Wang LL , Shao ZS , Chang YZ
Published: August 2011

Using variable separation approach and series solving method of differential equations, analytical solutions for temperature and thermo-mechanical stresses in cross-ply laminated composite cylinder with finite length are presented in this article. The cylinder is assumed to be simply supported at its two ends and is subjected to non-uniform thermal and mechanical loadings on the inner and outer surfaces. As an example, numerical results of temperature distribution, stress fields, and interlayer stresses of a four-layer laminated composite cylinder are graphically presented and briefly discussed.
Mycophenolate mofetil as a maintenance therapy for lupus-related diffuse alveolar hemorrhage: a case report
Authors: Rashidi A Al , Alajmi M , Hegazi MO
Published: August 2011

Diffuse alveolar hemorrhage (DAH) is a life-threatening complication of systemic lupus erythematosus (SLE). Cases complicated with DAH often have active SLE with multi-organ involvement, especially lupus nephritis. We describe a rare case of DAH as the first presenting manifestation of SLE in the absence of lupus nephritis. Remission was induced by IV methylprednisolone, IV cyclophosphamide, and plasmapheresis. Further cycles of cyclophosphamide were prevented by recurrent infections. Maintenance of remission was successfully achieved with oral mycophenolate mofetil 1 g twice daily, with a good control of SLE and without further DAH episodes.
Visual Cues for Person-centered Communication
Authors: Williams Kristine , Harris Brynn , Lueger Amy , Ward Kathleen , Wassmer Rebecca , Weber Amy
Published: August 2011

Nursing home communication is frequently limited and task-focused and fails to affirm resident personhood. We tested the feasibility and effects of automated digital displays of resident photographs to remind staff ( N = 11) of resident ( n = 6) personhood. Historical photographs were displayed in digital photo frames mounted in each resident’s room. To evaluate the intervention’s effects, staff–resident conversations were audio-recorded prior to displaying the frames and repeated 2 weeks and 3 months later. Conversations were transcribed and statements were topic coded (task-focused vs. interpersonal). Staff person-centered talk increased from 11% to 32% ( z = 2.37, p = .02) after the intervention and task-talk decreased from 64% to 40%. Resident interpersonal topics increased from 20% to 37%. Staff statements increased from 29 at baseline, to 37 postintervention, and 41 at 3-month follow-up and resident engagement and reminiscence also increased. Effects were reduced after 3 months. Automated photo displays are an easily implemented, low-cost intervention to promote person-centered communication.
Educational Outcomes Associated With Providing a Comprehensive Guidelines Program About Nursing Care of Preterm Neonates Receiving Total Parenteral Nutrition
Authors: Al-Rafay Safy S. , Al-Sharkawy Sabah S.
Published: August 2011

Poor understanding or practice of Total Parenteral Nutrition (TPN) causes devastating complications. Therefore, good Neonatal Intensive Care Unit (NICU) nursing care for preterm neonates and close monitoring of complications is essential for successful TPN therapy. The study was conducted in NICU at Ain Shams University Hospital in Cairo, Egypt, using a quasi-experimental research design with prepost intervention assessments. Data was collected using a self-administered questionnaire sheet and an observation checklist (prepost format) and developed a comprehensive guidelines program about nursing care of TPN of preterm neonates. Results revealed that the program had a significant positive impact on nurses’ knowledge and practice outcomes.
The Additive Effects of Ischemic Postconditioning and Cyclosporine-A on Nitric Oxide Activity and Functions of Diabetic Myocardium Injured by Ischemia/Reperfusion
Authors: Badalzadeh Reza , Mohammadi Mustafa , Najafi Moslem , Ahmadiasl Naser , Farajnia Safar , Ebrahimi Hadi
Published: August 2011

Background: The interaction of diabetes with cardioprotection by postconditioning in ischemia/reperfusion injury remains unclear. The aim of this study was to investigate the concomitant effects of ischemic postconditioning (IPostC) and cyclosporine-A (CsA) on nitric oxide (NO) content and parameters of cardiac function of the diabetic myocardium injured by ischemia/reperfusion. Methods: Diabetes was induced by single injection of streptozotocin (50 mg/kg; intraperitoneally [ip]) in Wistar rats (250-320 g) and the diabetic period was 8 weeks. The hearts (n = 96) were removed quickly, mounted on Langendorff apparatus, and then subjected to 30-minute regional ischemia followed by 45-minute reperfusion. Ischemic postconditioning was induced by 3 cycles of 30-second reperfusion/ischemia at the onset of reperfusion. Myocardial function was measured throughout the experiment, and infarct size (IS) was identified by triphenyltetrazolium chloride (TTC) staining. Total amounts of NO metabolites were determined using Griess method and enzyme-linked immunosorbent assay (ELISA) reader. Results: Administration of either IPostC or CsA alone in nondiabetic animals significantly improved myocardial function and reduced the ISs (28% ± 1.9% or 23% ± 2.0% vs 41% ± 2.9% of the risk zone [RZ], respectively; P < .01), but they had no effect on diabetic hearts (35% ± 1.8% or 32% ± 2.1% vs 39% ± 3.1%, respectively). In addition, myocardial NO level was significantly increased by IPostC only in nondiabetic animals (P < .01). However, after administration of CsA (5 minutes before and 10 minutes after the onset of reperfusion) in postconditioned animals, the cardioprotective and NO-enhancing effects of IPostC were restored in diabetic rats (IS: 21% ± 1.1% vs 39% ± 3.1%), similar to those in nondiabetic controls (19% ± 1.3% vs 41% ± 2.9%; P < .01). Conclusion: The present study indicated that IPostC or CsA failed to affect NO levels and failed to protect the diabetic myocardium against ischemia/reperfusion injury. Moreover, concomitant administration of CsA and IPostC at reperfusion can increase NO content and protect the diabetic myocardium.
Nonclinical Safety Assessment of a Synthetic Peptide Thrombopoietin Agonist
Authors: Knight Elaine , Eichenbaum Gary , Hillsamer Verna , Greway Tony , Tonelli Alfred , Han-Hsu Helen , Zakszewski Cindy , Yurkow Edward , Shukla Umesh , End David , Louden Calvert
Published: August 2011

RWJ-800088 is a novel, potent polyethylene glycol (PEG)-conjugated thrombopoietin (TPO) mimetic that increases platelet levels and protects against thrombocytopenia. A nonclinical safety program was customized for this peptide that takes into account its protein-like structure, synthetic chemical nature, agonist pharmacologic activity, and mode of administration. In repeat-dose toxicity studies, the salient findings were dose-related increases in circulating platelet counts, mean platelet volume, and megakaryocytes in the bone marrow with no antibody formation. Reversible myelofibrosis and hyperostosis were observed in rats, but not dogs, when the circulating platelet levels exceeded 3× those of vehicle controls. The bone effects were due to the exaggerated pharmacologic effect and excessive stimulation and elevation of megakaryocytes by TPO, which results in intramedullary proliferation of fibroblasts and mesenchymal cells followed by osseous metaplasia. These findings support the use of platelet elevations of >3× as a stopping criterion to prevent potential adverse bone-related effects in humans.
Genetic variations within the OPA1 gene are not associated with neuromyelitis optica
Authors: Sitarz Kamil S , Yu-Wai-Man Patrick , Hudson Gavin , Jacob Anu , Boggild Mike , Horvath Rita , Chinnery Patrick F
Published: August 2011

Neuromyelitis optica (NMO) is an idiopathic demyelinating disease which predominantly affects the optic nerve and spinal cord. Multiplex NMO pedigrees have been reported but the genetic risk factors conferring this increased familial susceptibility have not yet been determined. OPA1 mutations have recently been identified in families with progressive visual failure and spastic paraparesis, raising the possibility that OPA1 genetic variants could contribute to the aetiology of NMO. We therefore screened for OPA1 in 32 patients with NMO. No pathogenic mutations were found, and none of the 13 single-nucleotide polymorphisms identified were associated with an increased risk of developing NMO.
Characterization of damage size in metallic plates using Lamb waves
Authors: Hu Ning , Cai Yindi , Zhu Guangjun , Tsuji Chihiro , Liu Yaolu , Alamusi  , Cao YanPing
Published: August 2011

By employing the Lamb waves for monitoring the structural integrity, a theory was proposed to approximately evaluate the damage size based on the reflection intensity information from the damage. First, to relate the wave reflection intensity to the size and shape of the damage, this theory was constructed for an arbitrary elliptical damage, which can be changed into a crack-like or a circular damage. Then, this theory was verified by employing the numerical results predicted by a powerful numerical approach for through-thickness elliptical holes in aluminum plates. Furthermore, experimental verification was also performed for through-thickness circular holes in aluminum plates. By assuming a damage of a circular shape, this theory was further extended to approximately predict the damage size using a coarse sensor/actuator network after identifying the damage location. To validate the proposed method, a four PZT transducer network was used to experimentally identify the locations and sizes of a circular hole and an elliptical hole in aluminum square plates.
Bending property of glass-fiber composite reinforced by 8-shape 3D woven fabric pretreated with hypo-atmospheric-pressure plasma
Authors: Liu Jihong , Jiang Hongxia
Published: August 2011

Hypo-atmospheric-pressure plasma was utilized to pretreat 8-shape three-dimensional (3D) woven fabric of glass fiber. After that, the bending property of composite reinforced by the 8-shape 3D woven fabric was researched. The results showed that the composite of pretreated time 1 min had maximum onset fracture load, while the composite of pretreated time 3 min had minimum onset fracture load. Moreover, the displacement of all samples was over 4 mm. By observing the scanning electron microscopy images of the fibers peeling from the composites, it could be found that the surface of the fiber became coarse after the 8-shape 3D woven fabrics were pretreated by atmospheric-pressure plasma. The coarse surface improved interfacial adhesion between fibers and resin; consequently, the onset fracture load of the composite was improved.
Factor XIIa regulates the structure of the fibrin clot independently of thrombin generation through direct interaction with fibrin
Authors: Konings Joke , Govers-Riemslag José W. P. , Philippou Helen , Mutch Nicola J. , Borissoff Julian I. , Allan Peter , Mohan Sumitra , Tans Guido , ten Cate Hugo , Ariëns Robert A. S.
Published: August 2011

Recent data indicate an important contribution of coagulation factor (F)XII to in vivo thrombus formation. Because fibrin structure plays a key role in clot stability and thrombosis, we hypothesized that FXII(a) interacts with fibrin(ogen) and thereby regulates clot structure and function. In plasma and purified system, we observed a dose-dependent increase in fibrin fiber density and decrease in turbidity, reflecting a denser structure, and a nonlinear increase in clot stiffness with FXIIa. In plasma, this increase was partly independent of thrombin generation, as shown in clots made in prothrombin-deficient plasma initiated with snake venom enzyme and in clots made from plasma deficient in FXII and prothrombin. Purified FXII and α-FXIIa, but not β-FXIIa, bound to purified fibrinogen and fibrin with nanomolar affinity. Immunostaining of human carotid artery thrombi showed that FXII colocalized with areas of dense fibrin deposition, providing evidence for the in vivo modulation of fibrin structure by FXIIa. These data demonstrate that FXIIa modulates fibrin clot structure independently of thrombin generation through direct binding of the N-terminus of FXIIa to fibrin(ogen). Modification of fibrin structure by FXIIa represents a novel physiologic role for the contact pathway that may contribute to the pathophysiology of thrombosis.
Role of ZBP-89 in human globin gene regulation and erythroid differentiation
Authors: Woo Andrew J. , Kim Jonghwan , Xu Jian , Huang Hui , Cantor Alan B.
Published: August 2011

The molecular mechanisms underlying erythroid-specific gene regulation remain incompletely understood. Closely spaced binding sites for GATA, NF-E2/maf, and CACCC interacting transcription factors play functionally important roles in globin and other erythroid-specific gene expression. We and others recently identified the CACCC-binding transcription factor ZBP-89 as a novel GATA-1 and NF-E2/mafK interacting partner. Here, we examined the role of ZBP-89 in human globin gene regulation and erythroid maturation using a primary CD34+ cell ex vivo differentiation system. We show that ZBP-89 protein levels rise dramatically during human erythroid differentiation and that ZBP-89 occupies key cis-regulatory elements within the globin and other erythroid gene loci. ZBP-89 binding correlates strongly with RNA Pol II occupancy, active histone marks, and high-level gene expression. ZBP-89 physically associates with the histone acetyltransferases p300 and Gcn5/Trrap, and occupies common sites with Gcn5 within the human globin loci. Lentiviral short hairpin RNAs knockdown of ZBP-89 results in reduced Gcn5 occupancy, decreased acetylated histone 3 levels, lower globin and erythroid-specific gene expression, and impaired erythroid maturation. Addition of the histone deacetylase inhibitor valproic acid partially reverses the reduced globin gene expression. These findings reveal an activating role for ZBP-89 in human globin gene regulation and erythroid differentiation.
Molecular predictors of response to decitabine in advanced chronic myelomonocytic leukemia: a phase 2 trial
Authors: Braun Thorsten , Itzykson Raphael , Renneville Aline , de Renzis Benoit , Dreyfus François , Laribi Kamel , Bouabdallah Krimo , Vey Norbert , Toma Andrea , Recher Christian , Royer Bruno , Joly Bertrand , Vekhoff Anne , Lafon Ingrid , Sanhes Laurence , Meurice Guillaume , Oréar Cédric , Preudhomme Claude , Gardin Claude , Ades Lionel , Fontenay Michaela , Fenaux Pierre , Droin Nathalie , Solary Eric ,   on behalf of the Groupe Francophone des Myélodysplasies
Published: August 2011

Hydroxyurea is the standard therapy of chronic myelomonocytic leukemia (CMML) presenting with advanced myeloproliferative and/or myelodysplastic features. Response to hypomethylating agents has been reported in heterogeneous series of CMML. We conducted a phase 2 trial of decitabine (DAC) in 39 patients with advanced CMML defined according to a previous trial. Median number of DAC cycles was 10 (range, 1-24). Overall response rate was 38% with 4 complete responses (10%), 8 marrow responses (21%), and 3 stable diseases with hematologic improvement (8%). Eighteen patients (46%) demonstrated stable disease without hematologic improvement, and 6 (15%) progressed to acute leukemia. With a median follow-up of 23 months, overall survival was 48% at 2 years. Mutations in ASXL1, TET2, AML1, NRAS, KRAS, CBL, FLT3, and janus kinase 2 (JAK2) genes, and hypermethylation of the promoter of the tumor suppressor gene TIF1γ, did not predict response or survival on DAC therapy. Lower CJUN and CMYB gene expression levels independently predicted improved overall survival. This trial confirmed DAC efficacy in approximately 40% of CMML patients with advanced myeloproliferative or myelodysplastic features and suggested that CJUN and CMYB expression could be potential biomarkers in this setting. This trial is registered at EudraCT (eudract.ema.europa.eu) as #2008-000470-21 and www.clinicaltrials.gov as #NCT01098084.
DNA methyltransferase 1 and DNA methylation patterning contribute to germinal center B-cell differentiation
Authors: Shaknovich Rita , Cerchietti Leandro , Tsikitas Lucas , Kormaksson Matthias , De Subhajyoti , Figueroa Maria E. , Ballon Gianna , Yang Shao Ning , Weinhold Nils , Reimers Mark , Clozel Thomas , Luttrop Karin , Ekstrom Tomas J. , Frank Jared , Vasanthakumar Aparna , Godley Lucy A. , Michor Franziska , Elemento Olivier , Melnick Ari
Published: August 2011

The phenotype of germinal center (GC) B cells includes the unique ability to tolerate rapid proliferation and the mutagenic actions of activation induced cytosine deaminase (AICDA). Given the importance of epigenetic patterning in determining cellular phenotypes, we examined DNA methylation and the role of DNA methyltransferases in the formation of GCs. DNA methylation profiling revealed a marked shift in DNA methylation patterning in GC B cells versus resting/naive B cells. This shift included significant differential methylation of 235 genes, with concordant inverse changes in gene expression affecting most notably genes of the NFkB and MAP kinase signaling pathways. GC B cells were predominantly hypomethylated compared with naive B cells and AICDA binding sites were highly overrepresented among hypomethylated loci. GC B cells also exhibited greater DNA methylation heterogeneity than naive B cells. Among DNA methyltransferases (DNMTs), only DNMT1 was significantly up-regulated in GC B cells. Dnmt1 hypomorphic mice displayed deficient GC formation and treatment of mice with the DNA methyltransferase inhibitor decitabine resulted in failure to form GCs after immune stimulation. Notably, the GC B cells of Dnmt1 hypomorphic animals showed evidence of increased DNA damage, suggesting dual roles for DNMT1 in DNA methylation and double strand DNA break repair.
Bone marrow–derived CMPs and GMPs represent highly functional proangiogenic cells: implications for ischemic cardiovascular disease
Authors: Wara Akm Khyrul , Croce Kevin , Foo ShiYin , Sun Xinghui , Icli Basak , Tesmenitsky Yevgenia , Esen Fehim , Rosenzweig Anthony , Feinberg Mark W.
Published: August 2011

Clinical studies using bone marrow–derived proangiogenic cells (PACs) have demonstrated modest improvements of function and/or perfusion of ischemic myocardium or skeletal muscle. Because the identities of these PACs and their functional ability to promote neovascularization remain poorly understood, it is possible that a subset of robust PACs exists but is obscured by the heterogeneous nature of this cell population. Herein, we found that common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs) preferentially differentiate into PACs compared with megakaryocyte-erythrocyte progenitors, hematopoietic stem cells, and common lymphoid progenitors. In vivo hindlimb ischemia studies and Matrigel plug assays verified the enhanced neovascularization properties uniquely associated with PACs derived from CMPs and GMPs. Taken together, these observations identify CMPs and GMPs as key bone marrow progenitors for optimal PAC function in vitro and in vivo and provide a foundation for novel therapeutic approaches to modulate angiogenesis.
Prognostic factors related to sequelae in childhood bacterial meningitis: Data from a Greek meningitis registry
Authors: Vasilopoulou Vasiliki A , Karanika Maria , Theodoridou Kalliopi , Katsioulis Antonios T , Theodoridou Maria N , Hadjichristodoulou Christos S
Published: August 2011

Background

Bacterial meningitis (BM) is a life-threatening disease, often related with serious complications and sequelae. Infants and children who survive bacterial meningitis often suffer neurological and other sequelae.

Methods

A total of 2,477 patients aged 1 month to 14 years old hospitalized in a Children's Hospital in Greece diagnosed with acute bacterial meningitis were collected through a Meningitis Registry, from 1974 to 2005. Clinical, laboratory and other parameters (sex, age, pathogen, duration of symptoms before and after admission) were evaluated through univariate and multivariate analysis with regard to sequelae. Analysis of acute complications were also studied but not included in the final model.

Results

The rate of acute complications (arthritis and/or subdural effusion) was estimated at 6.8% (152 out of 2,251 patients, 95%CI 5.8-7.9) while the rate of sequelae (severe hearing loss, ventriculitis, hydrocephalus or seizure disorder) among survivors was estimated at 3.3% (73 out of 2,207 patients, 95%CI 2.6-4.2). Risk factors on admission associated with sequelae included seizures, absence of hemorrhagic rash, low CSF glucose, high CSF protein and the etiology of meningitis. A combination of significant prognostic factors including presence of seizures, low CSF glucose, high CSF protein, positive blood culture and absence of petechiae on admission presented an absolute risk of sequelae of 41.7% (95%CI 15.2-72.3).

Conclusions

A combination of prognostic factors of sequelae in childhood BM may be of value in selecting patients for more intensive therapy and in identifying possible candidates for new treatment strategies.
Non-pharmacological treatment of hypertension in primary health care: A comparative clinical trial of two education strategies in health and nutrition
Authors: Ribeiro Amanda G , Ribeiro Sônia MR , Dias Cristina MGC , Ribeiro Andréia Q , Castro Fátima AF , Suárez-Varela Maria M , Cotta Rosângela MM
Published: August 2011

Background

Poor adherence to non-pharmacological treatment of hypertension represents a serious challenge for public health policies in several countries. This study was conducted to compare two intervention strategies regarding the adherence of adult women to dietary changes recommended for the treatment of hypertension in a community covered by Primary Health Care Unit.

Methods

This study is a randomized controlled trial of a sample composed of 28 women with hypertension enrolled in the Primary Health Care Unit located in the urban area of southeastern Brazil. The participants were already undergoing treatment for hypertension but devoid of nutritional care; and were divided into two groups, each composed of 14 individuals, who received interventions that consisted of two different strategies of nutritional guidance: monthly health education workshops alone (Group 1) and combined with family orientation through home visits (Group 2). Adherence to nutritional guidelines was evaluated by dietary, anthropometric, clinical and serum biochemical parameters, measured before and after the interventions. Knowledge on control and risk of hypertension was also investigated. The study lasted five months.

Results

Mean age was 55.6 (± 2.8) and 50.7 (± 6.5) in the groups 1 and 2, respectively. The home orientation strategy promoted greater adherence to dietary changes, leading to a statistically significant improvement in the clinical, anthropometric, biochemical and dietary parameters. The group 2 reduced the consumption of risk foods (p = 0.01), oil (p = 0.002) and sugar (p = 0.02), and decreased body mass index (-0.7 kg/m2; p = 0.01); waist circumference (-4.2 cm; p = 0.001), systolic blood pressure (-13 mm HG; p = 0.004) and glycemia (-18.9 mg/dl; p = 0. 01). In group 1 only waist circumference (-2 cm; p = 0.01) changed significantly.

Conclusion

Nutritional orientations at the household level were more effective with regard to the adherence of individuals to non-pharmacological treatment of hypertension, regarding the reduction of clinical and behavioral risk parameters.
Effectiveness of interventions to improve the health and housing status of homeless people: a rapid systematic review
Authors: Fitzpatrick-Lewis Donna , Ganann Rebecca , Krishnaratne Shari , Ciliska Donna , Kouyoumdjian Fiona , Hwang Stephen W
Published: August 2011

Background

Research on interventions to positively impact health and housing status of people who are homeless has received substantially increased attention over the past 5 years. This rapid review examines recent evidence regarding interventions that have been shown to improve the health of homeless people, with particular focus on the effect of these interventions on housing status.

Methods

A total of 1,546 articles were identified by a structured search of five electronic databases, a hand search of grey literature and relevant journals, and contact with experts. Two reviewers independently screened the first 10% of titles and abstracts for relevance. Inter-rater reliability was high and as a result only one reviewer screened the remaining titles and abstracts. Articles were included if they were published between January 2004 and December 2009 and examined the effectiveness of an intervention to improve the health or healthcare utilization of people who were homeless, marginally housed, or at risk of homelessness. Two reviewers independently scored all relevant articles for quality.

Results

Eighty-four relevant studies were identified; none were of strong quality while ten were rated of moderate quality. For homeless people with mental illness, provision of housing upon hospital discharge was effective in improving sustained housing. For homeless people with substance abuse issues or concurrent disorders, provision of housing was associated with decreased substance use, relapses from periods of substance abstinence, and health services utilization, and increased housing tenure. Abstinent dependent housing was more effective in supporting housing status, substance abstinence, and improved psychiatric outcomes than non-abstinence dependent housing or no housing. Provision of housing also improved health outcomes among homeless populations with HIV. Health promotion programs can decrease risk behaviours among homeless populations.

Conclusions

These studies provide important new evidence regarding interventions to improve health, housing status, and access to healthcare for homeless populations. The additional studies included in this current review provide further support for earlier evidence which found that coordinated treatment programs for homeless persons with concurrent mental illness and substance misuse issues usually result in better health and access to healthcare than usual care. This review also provides a synthesis of existing evidence regarding interventions that specifically support homeless populations with HIV.
Aspirin-triggered lipoxin A4attenuates LPS-induced pro-inflammatory responses by inhibiting activation of NF-κB and MAPKs in BV-2 microglial cells
Authors: Wang Yan-Ping , Wu Yan , Li Long-Yan , Zheng Jin , Liu Ren-Gang , Zhou Jie-Ping , Yuan Shi-Ying , Shang You , Yao Shang-Long
Published: August 2011

Background

Microglial activation plays an important role in neurodegenerative diseases through production of nitric oxide (NO) and several pro-inflammatory cytokines. Lipoxins (LXs) and aspirin-triggered LXs (ATLs) are considered to act as 'braking signals' in inflammation. In the present study, we investigated the effect of aspirin-triggered LXA4 (ATL) on infiammatory responses induced by lipopolysaccharide (LPS) in murine microglial BV-2 cells.

Methods

BV-2 cells were treated with ATL prior to LPS exposure, and the effects of such treatment production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α) were analysed by Griess reaction, ELISA, western blotting and quantitative RT-PCR. Moreover, we investigated the effects of ATL on LPS-induced nuclear factor-κB (NF-κB) activation, phosphorylation of mitogen-activated protein kinases (MAPKs) and activator protein-1 (AP-1) activation.

Results

ATL inhibited LPS-induced production of NO, IL-1β and TNF-α in a concentration-dependent manner. mRNA expressions for iNOS, IL-1β and TNF-α in response to LPS were also decreased by ATL. These effects were inhibited by Boc-2 (a LXA4 receptor antagonist). ATL significantly reduced nuclear translocation of NF-κB p65, degradation of the inhibitor IκB-α, and phosphorylation of extracellular signal-regulated kinase (ERK) and p38 MAPK in BV-2 cells activated with LPS. Furthermore, the DNA binding activity of NF-κB and AP-1 was blocked by ATL.

Conclusions

This study indicates that ATL inhibits NO and pro-inflammatory cytokine production at least in part via NF-κB, ERK, p38 MAPK and AP-1 signaling pathways in LPS-activated microglia. Therefore, ATL may have therapeutic potential for various neurodegenerative diseases.
IPNV with high and low virulence: host immune responses and viral mutations during infection
Authors: Skjesol Astrid , Skjæveland Ingrid , Elnæs Marianne , Timmerhaus Gerrit , Fredriksen Børge N , Jørgensen Sven Martin , Krasnov Aleksei , Jørgensen Jorunn B
Published: August 2011

Background

Infectious pancreatic necrosis virus (IPNV) is an aquatic member of theBirnaviridaefamily that causes widespread disease in salmonids. IPNV is represented by multiple strains with markedly different virulence. Comparison of isolates reveals hyper variable regions (HVR), which are presumably associated with pathogenicity. However little is known about the rates and modes of sequence divergence and molecular mechanisms that determine virulence. Also how the host response may influence IPNV virulence is poorly described.

Methods

In this study we compared two field isolates of IPNV (NFH-Ar and NFH-El). The sequence changes, replication and mortality were assessed following experimental challenge of Atlantic salmon. Gene expression analyses with qPCR and microarray were applied to examine the immune responses in head kidney.

Results

Significant differences in mortality were observed between the two isolates, and viral load in the pancreas at 13 days post infection (d p.i.) was more than 4 orders of magnitude greater for NFH-Ar in comparison with NFH-El. Sequence comparison of five viral genes from the IPNV isolates revealed different mutation rates and Ka/Ks ratios. A strong tendency towards non-synonymous mutations was found in the HRV of VP2 and in VP3. All mutations in VP5 produced precocious stop codons. Prior to the challenge, NFH-Ar and NFH-El possessed high and low virulence motifs in VP2, respectively. Nucleotide substitutions were noticed already during passage of viruses in CHSE-214 cells and their accumulation continued in the challenged fish. The sequence changes were notably directed towards low virulence. Co-ordinated activation of anti-viral genes with diverse functions (IFN-a1 and c, sensors - Rig-I, MDA-5, TLR8 and 9, signal transducers - Srk2, MyD88, effectors - Mx, galectin 9, galectin binding protein, antigen presentation - b2-microglobulin) was observed at 13 d p.i. (NFH-Ar) and 29 d p.i. (both isolates).

Conclusions

Mortality and expression levels of the immune genes were directly related to the rate of viral replication, which was in turn associated with sequences of viral genes. Rapid changes in the viral genome that dramatically reduced virus proliferation might indicate a higher susceptibility to protective mechanism employed by the host. Disease outbreak and mortality depend on a delicate balance between host defence, regulation of signalling cascades and virus genomic properties.
The relation between cartilage biomarkers (C2C, C1,2C, CS846, and CPII) and the long-term outcome of rheumatoid arthritis patients within the CAMERA trial
Authors: Bakker Marije F , Verstappen Suzanne MM , Welsing Paco MJ , Jacobs Johannes WG , Jahangier Zalima N , van der Veen Maaike J , Bijlsma Johannes WJ , Lafeber Floris PJG ,   the Utrecht Arthritis Cohort study group
Published: August 2011

Introduction

The aim of this study was to investigate whether serum biomarker levels of C2C, C1,2C, CS846, and CPII can predict the long-term course of disease activity and radiographic progression early in the disease course of rheumatoid arthritis (RA).

Methods

In patients in the CAMERA trial, levels of biomarkers were evaluated at baseline and after 1 year of treatment. Relations of (changes in) biomarker values with the mean yearly radiographic progression rate and mean disease activity over a 5-year period were evaluated by using regression analysis. The added predictive value of biomarkers over established predictors for long-term outcome was analyzed by multiple linear regression analysis.

Results

Of 133 patients, serum samples were available at baseline and after 1 year of treatment. In the regression analysis C1,2C at baseline, the change in C2C, C1,2C, and the sum of the standardized changes in C2C + C1,2C scores were statistically significantly associated with the mean yearly radiographic progression rate; the change in CPII was associated with the mean disease activity over 5 years of treatment. In the multiple linear regression analysis, only the change in C1,2C was of added predictive value (P = 0.004) for radiographic progression. Explained variances of models for radiographic progression and disease activity were low (0.28 and 0.34, respectively), and the biomarkers only marginally improved the explained variance.

Conclusions

The change in C1,2C in the first year after onset of RA has a small added predictive value for disease severity over a 5-year period, but the predictive value of this biomarker combined with current predictive factors is too small to be of use for individual patients.