bluuebunny/crossref_metadata_2025 huggingface dataset:
A Biodegradable Polymeric Carrier Based on PEG for Drug Delivery
Authors: Mero Anna , Schiavon Oddone , Pasut Gianfranco , Veronese Francesco M. , Emilitri Elisa , Ferruti Paolo
Published: May 2009

A biodegradable copolymer (PEG- fum), based on poly(ethylene glycol) (PEG) and fumarate ( fum) units, was synthesized and studied as a drug carrier. PEG and fum were linked together by ester bonds to confer biodegradability to the polymeric backbone in vivo. Hence, this copolymer can be used with molecular weights above the kidney clearance threshold for PEG without body accumulation. The PEG- fum was designed to be a high drug loading carrier due to the fumarate units, thus, overcoming the limitations of linear PEGs. Suitable reactive groups for drug coupling were added by reacting fumarate with tioglycolic acid (TGA). The pendant TGA carboxylic groups were conjugated to the camptothecin derivative, SN38, taxol, and epirubicin. The SN38 and taxol linked to the PEG- fum-(TGA) increased their solubility 15- and 100-fold, respectively. The rate of SN38 release in plasma was adequate for prolonged circulation n vivoi, while taxol was rapidly hydrolyzed. This relatively fast degradation could hamper the conjugate from accumulating in the tumor tissue by enhanced permeability and retention effect (EPR). Instead, EPR effect could be exploited with the epirubicin conjugate coupled by means of a hydrazone bond. This linkage provides good blood stability, while readily cleaved in acidic environment like those in endosomes and lysosomes. Therefore, the drug is released intercellularly in its active form only after, thus reducing toxic effects.
Effects of Starch/ Polycaprolactone-based Blends for Spinal Cord Injury Regeneration in Neurons/Glial Cells Viability and Proliferation
Authors: Salgado A.J. , Sousa R.A. , Fraga J.S. , Pego J.M. , Silva B.A. , Malva J.O. , Neves N.M. , Reis R.L. , Sousa N.
Published: May 2009

Spinal cord injury (SCI) leads to drastic alterations on the quality of life of afflicted individuals. With the advent of Tissue Engineering and Regenerative Medicine where approaches combining biomaterials, cells and growth factors are used, one can envisage novel strategies that can adequately tackle this problem. The objective of this study was to evaluate a blend of starch with poly(ε-caprolactone) (SPCL) aimed to be used for the development of scaffolds spinal cord injury (SCI) repair. SPCL linear parallel filaments were deposited on polystyrene coverslips and assays were carried out using primary cultures of hippocampal neurons and glial cells. Light and fluorescence microscopy observations revealed that both cell populations were not negatively affected by the SPCL-based biomaterial. MTS and total protein quantification indicated that both cell viability and proliferation rates were similar to controls. Both neurons and astrocytes occasionally contacted the surface of SPCL filaments through their dendrites and cytoplasmatic processes, respectively, while microglial cells were unable to do so. Using single cell [Ca2+ ]i imaging, hippocampal neurons were observed growing within the patterned channels and were functional as assessed by the response to a 30 mM KCl stimulus. The present data demonstrated that SPCL-based blends are potentially suitable for the development of scaffolds in SCI regenerative medicine.
An Item-Level Psychometric Analysis of the Personality Assessment Inventory
Authors: Siefert Caleb J. , Sinclair Samuel J. , Kehl-Fie Kendra A. , Blais Mark A.
Published: May 2009

Multi-item multiscale self-report measures are increasingly used in inpatient assessments. When considering a measure for this setting, it is important to evaluate the psychometric properties of the clinical scales and items to ensure that they are functioning as intended in a highly distressed clinical population. The present study examines scale properties for a self-report measure frequently employed in inpatient assessments, the Personality Assessment Inventory (PAI). In addition to examining internal consistency statistics, this study extends prior PAI research by considering key issues related to inpatient assessment (e.g., scale distinctiveness, ceiling effects). Coefficient alphas, interitem correlations, and item— scale relationships suggest that the PAI clinical scales and subscales are internally consistent. Items for respective clinical scales generally showed significantly higher item—scale correlations with their intended scale (as compared with their item—scale correlation with scales they were not intended to measure). In addition, scales’ coefficient alpha scores were higher than their interscale correlations. Taken as a whole, these results support the hypothesis that PAI scales were measuring relatively distinct constructs in this inpatient sample. Findings are discussed with regard to the implications for scale interpretation in inpatient assessment, functioning of individual scales and subscales, and functioning of specific items. Limitations of the present study and directions for future research are discussed.
Assessing the Universal Structure of Personality in Early Adolescence
Authors: De Fruyt Filip , De Bolle Marleen , McCrae Robert R. , Terracciano Antonio , Costa Paul T. ,   Collaborators of the Adolescent Personality Profiles of Cultures Project
Published: May 2009

The structure and psychometric characteristics of the NEO Personality Inventory—3 (NEO-PI-3), a more readable version of the Revised NEO Personality Inventory (NEO-PI-R), are examined and compared with NEO-PI-R characteristics using data from college student observer ratings of 5,109 adolescents aged 12 to 17 years from 24 cultures. Replacement items in the PI-3 showed on average stronger item—total correlations and slightly improved facet reliabilities compared with the NEO-PI-R in both English- and non-English-speaking samples. NEO-PI-3 replacement items did not substantially affect scale means compared with the original scales. Analyses across and within cultures confirmed the intended factor structure of both versions when used to describe young adolescents. The authors discuss implications of these cross-cultural findings for the advancement of studies in adolescence and personality development across the lifespan.
Plasminogen Activator Inhibitor-1 (PAI-1) Gene 4G/5G Promoter Polymorphism is Seen in Higher Frequency in the Indian Patients With Deep Vein Thrombosis
Authors: Mohammed Suhail Akhter  , Biswas Arijit , Ranjan Ravi , Meena Arvind , Birendra Kumar Yadav  , Sharma Amit , Saxena Renu
Published: May 2009

Introduction: A number of prothrombotic and fibrinolytic disorders may lead to venous thrombosis. A 4G/5G polymorphism located in the promoter region of plasminogen activator inhibitor-1 (PAI-1) gene has been found to be commonly associated with the levels of PAI-1 and might be a risk factor for deep vein thrombosis (DVT). The aim of this study was to look for the potential association of this polymorphism with DVT in the Asian Indian population. Material and methods: A total of 110 consecutive patients (M:F = 62:48) with idiopathic DVT and equal number of age- and sex-matched healthy controls were the study participants. All study participants were typed for the PAI-1 4G/ 5G polymorphism, factor V Leiden, factor V Hong Kong/Cambridge mutations, and HR2 haplotype. Result: The variant allele for the PAI-1 4G/5G polymorphism showed both genotypic (P = .0013, χ2 = 10.303; odds ratio [OR] = 3.75) as well as allelic association (P = .0004, χ2 = 12.273; OR = 1.99) with DVT. Factor V Leiden and factor V HR2 haplotype were observed in 10 (9.0%) and 13 (11.8%) patients, respectively. None of the study participants showed the factor V Hong Kong Cambridge mutations. Conclusion: Our study shows the association of 4G allele with DVT in Asian Indian population. The higher prevalence of 4G polymorphism in patients with DVT (compared with controls) seen in our study is in concordance with previous reports from the Caucasian population.
Self-Reported ADHD Symptoms Among College Students
Authors: Mitchell John T. , Knouse Laura E. , Nelson-Gray Rosemery O. , Kwapil Thomas R.
Published: May 2009

Objective: The effect of manipulating item positioning on self-reported ADHD symptoms was examined. We assessed whether listing DSM-IV ADHD symptoms serially or interspersed affected (a) the correlation between ADHD symptoms and (b) the rate of symptom endorsement. Method: In Study 1, an undergraduate sample (n = 102) completed a measure that listed DSM-IV ADHD symptoms serially and a measure that interspersed DSM-IV ADHD items among non-ADHD symptoms. In Study 2, a separate undergraduate sample (n = 240) completed a measure that listed DSM-IV ADHD symptoms serially and another ADHD measure that interspersed DSM-IV ADHD items among non- DSM-IV ADHD items. Results: Item positioning did not affect the correlation between symptoms, but did reveal a significant bias in the rate of symptom endorsements. Conclusion: These findings suggest that there is significant variability in ADHD symptom endorsements resulting from item positioning. This effect has implications for clinical assessment and epidemiological research of ADHD among college students. (J. of Att. Dis. 2009; 13(2) 154-160)
Effects of Atrazine and Fenoxaprop-Ethyl on Capacitation and the Acrosomal Reaction in Boar Sperm
Authors: Maravilla-Galván Ramiro , Fierro Reyna , González-Márquez Humberto , Gómez-Arroyo Sandra , Jiménez Irma , Betancourt Miguel
Published: May 2009

Atrazine is a herbicide of the chloro-s-triazine family. It inhibits photosynthesis in plants and is an endocrine disruptor, but its effects on human health are controversial. Fenoxaprop-ethyl, an aryloxy phenoxyalkanoic acid herbicide, inhibits the biosynthesis of fatty acids and provokes depolarization of membranes. The aim of this study is to evaluate the in vitro effects of both herbicides on capacitation, spontaneous acrosome reaction (SAR) and progesterone-induced acrosome reaction (PIAR) in boar sperm. Sperm capacitation is done in TALP-HEPES media for 4 hours. Capacitation and SAR are evaluated immediately; PIAR, 30 minutes later. LC50 for fenoxaprop-ethyl is 60 mM and 40 mM for atrazine. Fenoxaprop-ethyl induces capacitation at 60 mM and SAR at all concentrations, also increases significantly PIAR. Atrazine decreased capacitation whereas increase significantly SAR and PIAR at all concentrations. It seems that fenoxaprop-ethyl and atrazine accelerate the capacitation and the acrosomal reaction, possibly via plasma membrane destabilization.
Menadione Reduction by Pharmacological Doses of Ascorbate Induces an Oxidative Stress That Kills Breast Cancer Cells
Authors: Beck Raphaël , Verrax Julien , Dejeans Nicolas , Taper Henryk , Calderon Pedro Buc
Published: May 2009

Oxidative stress generated by ascorbate-driven menadione redox cycling kills MCF7 cells by a concerted mechanism including glycolysis inhibition, loss of calcium homeostasis, DNA damage and changes in mitogen activated protein kinases (MAPK) activities. Cell death is mediated by necrosis rather than apoptosis or macroautophagy. Neither 3-methyladenine nor Z-VAD affects cytotoxicity by ascorbate/menadione (Asc/Men). BAPTA-AM, by restoring cellular capacity to reduce MTT, underlines the role of calcium in the necrotic process. Oxidative stress-mediated cell death is shown by the opposite effects of N-acetylcysteine and 3-aminotriazole. Moreover, oxidative stress induces DNA damage (protein poly-ADP-ribosylation and γ-H2AX phosphorylation) and inhibits glycolysis. Asc/Men deactivates extracellular signal-regulated kinase (ERK) while activating p38, suggesting an additional mechanism to kill MCF7 cells. Since ascorbate is taken up by cancer cells and, due to their antioxidant enzyme deficiency, oxidative stress should affect cancer cells to a greater extent than normal cells. This differential sensitivity may have clinical applications.
Preliminary Evidence of a Genetic Association Between Tumor Necrosis Factor Alpha and the Severity of Sleep Disturbance and Morning Fatigue
Authors: Aouizerat Bradley E. , Dodd Marylin , Lee Kathryn , West Claudia , Paul Steven M. , Cooper Bruce A. , Wara William , Swift Patrick , Dunn Laura B. , Miaskowski Christine
Published: May 2009

Although fatigue and sleep disturbance are prevalent symptoms in oncology patients and their family caregivers, little is known about the factors that contribute to interindividual variability in symptom severity ratings as well as in their underlying biological mechanisms. In this study, we sought to determine whether a functional genetic variation in a prominent proinflammatory cytokine, tumor necrosis factor-alpha (TNFA-308G>A [rs1800629] promoter polymorphism) was associated with overall ratings of sleep disturbance and fatigue as well as with the trajectories of these symptoms. Over 6 months, participants completed standardized measures of sleep disturbance and fatigue. Multiple linear regression was used to assess the effect of the TNFA genotype and other covariates on mean sleep disturbance and fatigue scores. Hierarchical linear modeling was used to determine the effect of TNFA genotype on the trajectories of these symptoms. Common allele homozygotes reported higher levels of sleep disturbance (p = .09) and morning fatigue (p = .02) than minor allele carriers. Multivariate analyses demonstrated that age and genotype were predictors of both mean symptom scores and the trajectories of these symptoms. Findings provide preliminary evidence of an association between a functional promoter polymorphism in the TNFA gene and the severity of sleep disturbance and morning fatigue in oncology patients and their family caregivers.
Influence of Seated Rocking on Blood Pressure in the Elderly: A Pilot Clinical Study
Authors: Pierce Carolyn , Pecen Janice , McLeod Kenneth J.
Published: May 2009

Patients with Alzheimer’s disease (AD) who rock for 1—2 hr per day in a rocking chair demonstrate significant improvements in depression, anxiety, and balance and a decrease in pain medication usage; however, the underlying basis for their responses remains unclear. Rocking with plantar flexion uses the calf muscles, enhancing lower limb fluid return to the heart, which should increase blood pressure (BP) and may, then, also increase cerebral perfusion. Accordingly, we tested the efficacy of rocking activity for increasing BP in healthy, older persons. In a pilot laboratory study of 24 healthy, White men and women aged 55—87 years, we observed that 30 min of steady rocking led to an average 12 mmHg increase in systolic blood pressure (SBP, p < .001) and a 3.6 mmHg average increase in diastolic blood pressure (DBP, p < .001). To determine the effect of using this intervention in a nonclinical setting, we tested a similar group of 7 participants at a senior center. In this setting, we observed an average increase in SBP of 27 mmHg (p < .001) and in DBP of 2.5 mmHg (p < .001) after 30 min of rocking. In a subgroup (n = 8) of hypotensive individuals (SBP < 110 mmHg after sitting quietly for 30 min) extracted from both settings, rocking raised the average SBP from <100 mmHg to approximately 120 mmHg. These results are consistent with the hypothesis that rocking can increase BP and, therefore, may enhance cerebral perfusion. This observation may play a fundamental role in designing nursing interventions focused on improvement of symptoms associated with AD.
The Payoff to Leadership in Teams
Authors: Deutscher Christian
Published: May 2009

In team sports, as well as in other group productions, some individuals are asked to show leadership skills. Although it is assumed that this ability is compensated monetarily, there is a lack of empirical evidence for this common thesis. Because in professional sports the team captains are expected to possess these leadership skills, this article will explore the impact of this ability on the salary. Controlling for individual player characteristics and performance indicators for players from the National Hockey League, the author shows that leadership ability is rewarded pecuniary by a wage premium between 21% and 35%.
Competitive Balance and Match Uncertainty in Grand-Slam Tennis
Authors: del Corral Julio
Published: May 2009

This article tests whether the increase in seeded players in tennis grand-slam tournaments from 16 to 32 in 2001 led to decreased competitive balance. In doing so, two alternative measures of competitive balance for single-elimination tournaments are proposed based on the performance of seeded players. Likewise, the differences in competitive balance due to gender and court surface are also analyzed. Additionally, using data from tennis grand-slam matches from 2005 to 2008, this article analyzed the determinants of ex post match level uncertainty with probit models.
Programmed death 1 signaling on chronic myeloid leukemia–specific T cells results in T-cell exhaustion and disease progression
Authors: Mumprecht Sabine , Schürch Christian , Schwaller Juerg , Solenthaler Max , Ochsenbein Adrian F.
Published: May 2009

Chronic myeloid leukemia (CML) is a malignant myeloproliferative disease with a characteristic chronic phase (cp) of several years before progression to blast crisis (bc). The immune system may contribute to disease control in CML. We analyzed leukemia-specific immune responses in cpCML and bcCML in a retroviral-induced murine CML model. In the presence of cpCML and bcCML expressing the glycoprotein of lymphocytic choriomeningitis virus as a model leukemia antigen, leukemia-specific cytotoxic T lymphocytes (CTLs) became exhausted. They maintained only limited cytotoxic activity, and did not produce interferon-γ or tumor necrosis factor-α or expand after restimulation. CML-specific CTLs were characterized by high expression of programmed death 1 (PD-1), whereas CML cells expressed PD-ligand 1 (PD-L1). Blocking the PD-1/PD-L1 interaction by generating bcCML in PD-1–deficient mice or by repetitive administration of αPD-L1 antibody prolonged survival. In addition, we found that PD-1 is up-regulated on CD8+ T cells from CML patients. Taken together, our results suggest that blocking the PD-1/PD-L1 interaction may restore the function of CML-specific CTLs and may represent a novel therapeutic approach for CML.
The prototype endothelial marker PAL-E is a leukocyte trafficking molecule
Authors: Keuschnigg Johannes , Henttinen Tiina , Auvinen Kaisa , Karikoski Marika , Salmi Marko , Jalkanen Sirpa
Published: May 2009

Pathologische Anatomie Leiden-endothelium antibody has been used for more than 20 years as a marker for vascular endothelium. Despite its widespread use, the target of this antibody was only recently identified as plasmalemma vesicle–associated protein-1 (PV-1). However, no function has been identified for this molecule. Here we report that activation of human umbilical vein endothelial cells with tumor necrosis factor-α resulted in a remarkable redistribution of PV-1 toward the peripheral areas of the cells. Furthermore, in vitro endpoint transmigration experiments showed that transcellularly migrating lymphocytes are surrounded by rings containing PV-1 and caveolin-1. Moreover, PV-1 associates physically with vimentin. In addition, administration of anti–PV-1 antibody during capillary flow assays resulted in a significant inhibition of lymphocyte transmigration through the endothelial cell layer, whereas rolling and adhesion were unaffected. In vivo blockage of PV-1 by an antibody in acute peritonitis and air pouch model resulted in a significant decrease in the number of migrating leukocytes. Here we thus define leukocyte transendothelial migration as the first known function for PV-1.
C/EBPα initiates primitive myelopoiesis in pluripotent embryonic cells
Authors: Chen Yaoyao , Costa Ricardo M. B. , Love Nick R. , Soto Ximena , Roth Martin , Paredes Roberto , Amaya Enrique
Published: May 2009

The molecular mechanisms that underlie the development of primitive myeloid cells in vertebrate embryos are not well understood. Here we characterize the role of cebpa during primitive myeloid cell development in Xenopus. We show that cebpa is one of the first known hematopoietic genes expressed in the embryo. Loss- and gain-of-function studies show that it is both necessary and sufficient for the development of functional myeloid cells. In addition, we show that cebpa misexpression leads to the precocious induction of myeloid cell markers in pluripotent prospective ectodermal cells, without the cells transitioning through a general mesodermal state. Finally, we use live imaging to show that cebpa-expressing cells exhibit many attributes of terminally differentiated myeloid cells, such as highly active migratory behavior, the ability to quickly and efficiently migrate toward wounds and phagocytose bacteria, and the ability to enter the circulation. Thus, C/EPBα is the first known single factor capable of initiating an entire myelopoiesis pathway in pluripotent cells in the embryo.
High prevalence of dysfibrinogenemia among patients with chronic thromboembolic pulmonary hypertension
Authors: Morris Timothy A. , Marsh James J. , Chiles Peter G. , Magaña Marisa M. , Liang Ni-Cheng , Soler Xavier , DeSantis Daniel J. , Ngo Debby , Woods Virgil L.
Published: May 2009

The mechanism by which chronic thromboembolic pulmonary hypertension (CTEPH) develops after acute pulmonary thromboembolism is unknown. We previously reported that fibrin from CTEPH patients is relatively resistant to fibrinolysis in vitro. In the present study, we performed proteomic, genomic, and functional studies on fibrin(ogen) to investigate whether abnormal fibrin(ogen) might contribute to the pathogenesis of CTEPH. Reduced and denatured fibrinogen from 33 CTEPH patients was subjected to liquid chromatography–mass spectrometry analysis. Fibrinogen from 21 healthy controls was used to distinguish atypical from commonly occurring mass peaks. Atypical peaks were further investigated by targeted genomic DNA sequencing. Five fibrinogen variants with corresponding heterozygous gene mutations (dysfibrinogenemias) were observed in 5 of 33 CTEPH patients: Bβ P235L/γ R375W, Bβ P235L/γ Y114H, Bβ P235L, Aα L69H, and Aα R554H (fibrinogensSan Diego I-V). Bβ P235L was found in 3 unrelated CTEPH patients. Functional analysis disclosed abnormalities in fibrin polymer structure and/or lysis with all CTEPH-associated mutations. These results suggest that, in some patients, differences in the molecular structure of fibrin may be implicated in the development of CTEPH after acute thromboembolism.
Integration of tomato reproductive developmental landmarks and expression profiles, and the effect of SUN on fruit shape
Authors: Xiao Han , Radovich Cheryll , Welty Nicholas , Hsu Jason , Li Dongmei , Meulia Tea , van der Knaap Esther
Published: May 2009

Background

Universally accepted landmark stages are necessary to highlight key events in plant reproductive development and to facilitate comparisons among species. Domestication and selection of tomato resulted in many varieties that differ in fruit shape and size. This diversity is useful to unravel underlying molecular and developmental mechanisms that control organ morphology and patterning. The tomato fruit shape gene SUN controls fruit elongation. The most dramatic effect of SUN on fruit shape occurs after pollination and fertilization although a detailed investigation into the timing of the fruit shape change as well as gene expression profiles during critical developmental stages has not been conducted.

Results

We provide a description of floral and fruit development in a red-fruited closely related wild relative of tomato, Solanum pimpinellifolium accession LA1589. We use established and propose new floral and fruit landmarks to present a framework for tomato developmental studies. In addition, gene expression profiles of three key stages in floral and fruit development are presented, namely floral buds 10 days before anthesis (floral landmark 7), anthesis-stage flowers (floral landmark 10 and fruit landmark 1), and 5 days post anthesis fruit (fruit landmark 3). To demonstrate the utility of the landmarks, we characterize the tomato shape gene SUN in fruit development. SUN controls fruit shape predominantly after fertilization and its effect reaches a maximum at 8 days post-anthesis coinciding with fruit landmark 4 representing the globular embryo stage of seed development. The expression profiles of the NILs that differ at sun show that only 34 genes were differentially expressed and most of them at a less than 2-fold difference.

Conclusion

The landmarks for flower and fruit development in tomato were outlined and integrated with the effect of SUN on fruit shape. Although we did not identify many genes differentially expressed in the NILs that differ at the sun locus, higher or lower transcript levels for many genes involved in phytohormone biosynthesis or signaling as well as organ identity and patterning of tomato fruit were found between developmental time points.
Head CT is of limited diagnostic value in critically ill patients who remain unresponsive after discontinuation of sedation
Authors: Balachandran Jay S , Jaleel Mairaj , Jain Manu , Mahajan Niraj , Kalhan Ravi , Balagani Rajesh , Donnelly Helen K , Greenstein Eugene , Mutlu Gökhan M
Published: May 2009

Background

Prolonged sedation is common in mechanically ventilated patients and is associated with increased morbidity and mortality. We sought to determine the diagnostic value of head computed tomography (CT) in mechanically ventilated patients who remain unresponsive after discontinuation of sedation.

Methods

A retrospective review of adult (age >18 years of age) patients consecutively admitted to the medical intensive care unit of a tertiary care medical center. Patients requiring mechanical ventilation for management of respiratory failure for longer than 72 hours were included in the study group. A group that did not have difficulty with awakening was included as a control.

Results

The median time after sedation was discontinued until a head CT was performed was 2 days (interquartile range 1.375–2 days). Majority (80%) of patients underwent head CT evaluation within the first 48 hours after discontinuation of sedation. Head CT was non-diagnostic in all but one patient who had a small subarachnoid hemorrhage. Twenty-five patients (60%) had a normal head CT. Head CT findings did not alter the management of any of the patients. The control group was similar to the experimental group with respect to demographics, etiology of respiratory failure and type of sedation used. However, while 37% of subjects in the control group had daily interruption of sedation, only 19% in the patient group had daily interruption of sedation (p < 0.05).

Conclusion

In patients on mechanical ventilation for at least 72 hours and who remain unresponsive after sedative discontinuation and with a non-focal neurologic examination, head CT is performed early and is of very limited diagnostic utility. Routine use of daily interruption of sedation is used in a minority of patients outside of a clinical trial setting though it may decrease the frequency of unresponsiveness from prolonged sedation and the need for head CT in patients mechanically ventilated for a prolonged period.
3.2 million stillbirths: epidemiology and overview of the evidence review
Authors: Lawn Joy E , Yakoob Mohammad Yawar , Haws Rachel A , Soomro Tanya , Darmstadt Gary L , Bhutta Zulfiqar A
Published: May 2009

More than 3.2 million stillbirths occur globally each year, yet stillbirths are largely invisible in global data tracking, policy dialogue and programme implementation. This mismatch of burden to action is due to a number of factors that keep stillbirths hidden, notably a lack of data and a lack of consensus on priority interventions, but also to social taboos that reduce the visibility of stillbirths and the associated family mourning. Whilst there are estimates of the numbers of stillbirths, to date there has been no systematic global analysis of the causes of stillbirths. The multiple classifications systems in use are often complex and are primarily focused on high-income countries. We review available data and propose a programmatic classification that is feasible and comparable across settings. We undertook a comprehensive global review of available information on stillbirths in order to 1) identify studies that evaluated risk factors and interventions to reduce stillbirths, 2) evaluate the level of evidence for interventions, 3) place the available evidence for interventions in a health systems context to guide programme implementation, and 4) elucidate key implementation, monitoring, and research gaps. This first paper in the series outlines issues in stillbirth data availability and quality, the global epidemiology of stillbirths, and describes the methodology and framework used for the review of interventions and strategies.
Identification of hematein as a novel inhibitor of protein kinase CK2 from a natural product library
Authors: Hung Ming-Szu , Xu Zhidong , Lin Yu-Ching , Mao Jian-Hua , Yang Cheng-Ta , Chang Pey-Jium , Jablons David M , You Liang
Published: May 2009

Background

Casein kinase 2 (CK2) is dysregulated in various human cancers and is a promising target for cancer therapy. To date, there is no small molecular CK2 inhibitor in clinical trial yet. With the aim to identify novel CK2 inhibitors, we screened a natural product library.

Methods

We adopted cell-based proliferation and CK2 kinase assays to screen CK2 inhibitors from a natural compound library. Dose-dependent response of CK2 inhibitors in vitro was determined by a radioisotope kinase assay. Western blot analysis was used to evaluate down stream Akt phosphorylation and apoptosis. Apoptosis was also evaluated by annexin-V/propidium iodide (PI) labeling method using flow cytometry. Inhibition effects of CK2 inhibitors on the growth of cancer and normal cells were evaluated by cell proliferation and viability assays.

Results

Hematein was identified as a novel CK2 inhibitor that is highly selective among a panel of kinases. It appears to be an ATP non-competitive and partially reversible CK2 inhibitor with an IC50 value of 0.55 μM. In addition, hematein inhibited cancer cell growth partially through down-regulation of Akt phosphorylation and induced apoptosis in these cells. Furthermore, hematein exerted stronger inhibition effects on the growth of cancer cells than in normal cells.

Conclusion

In this study, we showed that hematein is a novel selective and cell permeable small molecule CK2 inhibitor. Hematein showed stronger growth inhibition effects to cancer cells when compared to normal cells. This compound may represent a promising class of CK2 inhibitors.
Within-host competitive exclusion among species of the anther smut pathogen
Authors: Gold Alexander , Giraud Tatiana , Hood Michael E
Published: May 2009

Background

Host individuals represent an arena in which pathogens compete for resources and transmission opportunities, with major implications for the evolution of virulence and the structure of populations. Studies to date have focused on competitive interactions within pathogen species, and the level of antagonism tends to increase with the genetic distance between competitors. Anther-smut fungi, in the genus Microbotryum, have emerged as a tractable model for within-host competition. Here, using two pathogen species that are frequently found in sympatry, we investigated whether the antagonism seen among genotypes of the same species cascades up to influence competition among pathogen species.

Results

Sequential inoculation of hosts showed that a resident infection most often excludes a challenging pathogen genotype, which is consistent with prior studies. However, the challenging pathogen was significantly more likely to invade the already-infected host if the resident infection was a conspecific genotype compared to challenges involving a closely related species. Moreover, when inter-specific co-infection occurred, the pathogens were highly segregated within the host, in contrast to intra-specific co-infection.

Conclusion

We show evidence that competitive exclusion during infection can be greater among closely related pathogen species than among genotypes within species. This pattern follows from prior studies demonstrating that genetic distance and antagonistic interactions are positively correlated in Microbotryum. Fungal vegetative incompatibility is a likely mechanism of direct competitive interference, and has been shown in some fungi to be effective both within and across species boundaries. For systems where related pathogen species frequently co-occur in the same host populations, these competitive dynamics may substantially impact the spatial segregation of pathogen species.
Acclimatory responses of the Daphnia pulex proteome to environmental changes. I. Chronic exposure to hypoxia affects the oxygen transport system and carbohydrate metabolism
Authors: Zeis Bettina , Lamkemeyer Tobias , Paul Rüdiger J , Nunes Frank , Schwerin Susanne , Koch Marita , Schütz Wolfgang , Madlung Johannes , Fladerer Claudia , Pirow Ralph
Published: May 2009

Background

Freshwater planktonic crustaceans of the genusDaphniashow a remarkable plasticity to cope with environmental changes in oxygen concentration and temperature. One of the key proteins of adaptive gene control inDaphnia pulexunder hypoxia is hemoglobin (Hb), which increases in hemolymph concentration by an order of magnitude and shows an enhanced oxygen affinity due to changes in subunit composition. To explore the full spectrum of adaptive protein expression in response to low-oxygen conditions, two-dimensional gel electrophoresis and mass spectrometry were used to analyze the proteome composition of animals acclimated to normoxia (oxygen partial pressure [Po2]: 20 kPa) and hypoxia (Po2: 3 kPa), respectively.

Results

The comparative proteome analysis showed an up-regulation of more than 50 protein spots under hypoxia. Identification of a major share of these spots revealed acclimatory changes for Hb, glycolytic enzymes (enolase), and enzymes involved in the degradation of storage and structural carbohydrates (e.g. cellubiohydrolase). Proteolytic enzymes remained constitutively expressed on a high level.

Conclusion

Acclimatory adjustments of theD. pulexproteome to hypoxia included a strong induction of Hb and carbohydrate-degrading enzymes. The scenario of adaptive protein expression under environmental hypoxia can be interpreted as a process to improve oxygen transport and carbohydrate provision for the maintenance of ATP production, even during short episodes of tissue hypoxia requiring support from anaerobic metabolism.
Spatiotemporal analysis of air pollution and asthma patient visits in Taipei, Taiwan
Authors: Chan Ta-Chien , Chen Mei-Lien , Lin I-Feng , Lee Cheng-Hua , Chiang Po-Huang , Wang Da-Wei , Chuang Jen-Hsiang
Published: May 2009

Background

Buffer analyses have shown that air pollution is associated with an increased incidence of asthma, but little is known about how air pollutants affect health outside a defined buffer. The aim of this study was to better understand how air pollutants affect asthma patient visits in a metropolitan area. The study used an integrated spatial and temporal approach that included the Kriging method and the Generalized Additive Model (GAM).

Results

We analyzed daily outpatient and emergency visit data from the Taiwan Bureau of National Health Insurance and air pollution data from the Taiwan Environmental Protection Administration during 2000–2002. In general, children (aged 0–15 years) had the highest number of total asthma visits. Seasonal changes of PM10, NO2, O3and SO2were evident. However, SO2showed a positive correlation with the dew point (r = 0.17, p < 0.01) and temperature (r = 0.22, p < 0.01). Among the four pollutants studied, the elevation of NO2concentration had the highest impact on asthma outpatient visits on the day that a 10% increase of concentration caused the asthma outpatient visit rate to increase by 0.30% (95% CI: 0.16%~0.45%) in the four pollutant model. For emergency visits, the elevation of PM10concentration, which occurred two days before the visits, had the most significant influence on this type of patient visit with an increase of 0.14% (95% CI: 0.01%~0.28%) in the four pollutants model. The impact on the emergency visit rate was non-significant two days following exposure to the other three air pollutants.

Conclusion

This preliminary study demonstrates the feasibility of an integrated spatial and temporal approach to assess the impact of air pollution on asthma patient visits. The results of this study provide a better understanding of the correlation of air pollution with asthma patient visits and demonstrate that NO2and PM10might have a positive impact on outpatient and emergency settings respectively. Future research is required to validate robust spatiotemporal patterns and trends.
Specific retention of the protostome-specific PsGEF may parallel with the evolution of mushroom bodies in insect and lophotrochozoan brains
Authors: Higuchi Nozomu , Kohno Keigo , Kadowaki Tatsuhiko
Published: May 2009

Background

Gene gain and subsequent retention or loss during evolution may be one of the underlying mechanisms involved in generating the diversity of metazoan nervous systems. However, the causal relationships acting therein have not been studied extensively.

Results

We identified the genePsGEF(protostome-specific GEF), which is present in all the sequenced genomes of insects and limpet but absent in those of sea anemones, deuterostomes, and nematodes. InDrosophila melanogaster, PsGEFencodes a short version of a protein with the C2 and PDZ domains, as well as a long version with the C2, PDZ, and RhoGEF domains through alternative splicing. Intriguingly, the exons encoding the RhoGEF domain are specifically deleted in theDaphnia pulexgenome, suggesting thatDaphniaPsGEF contains only the C2 and PDZ domains. Thus, the distribution of PsGEF containing the C2, PDZ, and RhoGEF domains among metazoans appears to coincide with the presence of mushroom bodies. Mushroom bodies are prominent neuropils involved in the processing of multiple sensory inputs as well as associative learning in the insect, platyhelminth, and annelid brains. In the adultDrosophilabrain,PsGEFis expressed in mushroom bodies, antennal lobe, and optic lobe, where it is necessary for the correct axon branch formation of alpha/beta neurons in mushroom bodies.PsGEFgenetically interacts withRac1but not other Rho family members, and the RhoGEF domain of PsGEF induces actin polymerization in the membrane, thus resulting in the membrane ruffling that is observed in cultured cells with activated forms of Rac.

Conclusion

The specific acquisition ofPsGEFby the last common ancestor of protostomes followed by its retention or loss in specific animal species during evolution demonstrates that there are some structural and/or functional features common between insect and lophotrochozoan nervous systems (for example, mushroom bodies), which are absent in all deuterostomes and cnidarians.PsGEFis therefore one of genes associated with the diversity of metazoan nervous systems.
A binary method for simple and accurate two-dimensional cursor control from EEG with minimal subject training
Authors: Kayagil Turan A , Bai Ou , Henriquez Craig S , Lin Peter , Furlani Stephen J , Vorbach Sherry , Hallett Mark
Published: May 2009

Background

Brain-computer interfaces (BCI) use electroencephalography (EEG) to interpret user intention and control an output device accordingly. We describe a novel BCI method to use a signal from five EEG channels (comprising one primary channel with four additional channels used to calculate its Laplacian derivation) to provide two-dimensional (2-D) control of a cursor on a computer screen, with simple threshold-based binary classification of band power readings taken over pre-defined time windows during subject hand movement.

Methods

We tested the paradigm with four healthy subjects, none of whom had prior BCI experience. Each subject played a game wherein he or she attempted to move a cursor to a target within a grid while avoiding a trap. We also present supplementary results including one healthy subject using motor imagery, one primary lateral sclerosis (PLS) patient, and one healthy subject using a single EEG channel without Laplacian derivation.

Results

For the four healthy subjects using real hand movement, the system provided accurate cursor control with little or no required user training. The average accuracy of the cursor movement was 86.1% (SD 9.8%), which is significantly better than chance (p = 0.0015). The best subject achieved a control accuracy of 96%, with only one incorrect bit classification out of 47. The supplementary results showed that control can be achieved under the respective experimental conditions, but with reduced accuracy.

Conclusion

The binary method provides naïve subjects with real-time control of a cursor in 2-D using dichotomous classification of synchronous EEG band power readings from a small number of channels during hand movement. The primary strengths of our method are simplicity of hardware and software, and high accuracy when used by untrained subjects.
Sternal plating for primary and secondary sternal closure; can it improve sternal stability?
Authors: Fawzy Hosam , Alhodaib Nasser , Mazer C. David , Harrington Alana , Latter David , Bonneau Daniel , Errett Lee , Mahoney James
Published: May 2009

Background

Sternal instability with mediastinitis is a very serious complication after median sternotomy. Biomechanical studies have suggested superiority of rigid plate fixation over wire cerclage for sternal fixation. This study tests the hypothesis that sternal closure stability can be improved by adding plate fixation in a human cadaver model.

Methods

Midline sternotomy was performed in 18 human cadavers. Four sternal closure techniques were tested: (1) approximation with six interrupted steel wires; (2) approximation with six interrupted cables; (3) closure 1 (wires) or 2 (cables) reinforced with a transverse sternal plate at the sixth rib; (4) Closure using 4 sternal plates alone. Intrathoracic pressure was increased in all techniques while sternal separation was measured by three pairs of sonomicrometry crystals fixed at the upper, middle and lower parts of the sternum until 2.0 mm separation was detected. Differences in displacement pressures were analyzed using repeated measures ANOVA and Regression Coefficients.

Results

Intrathoracic pressure required to cause 2.0 mm separation increased significantly from 183.3 ± 123.9 to 301.4 ± 204.5 in wires/cables alone vs. wires/cables plus one plate respectively, and to 355.0 ± 210.4 in the 4 plates group (p < 0.05). Regression Coefficients (95% CI) were 120 (47–194) and 142 (66–219) respectively for the plate groups.

Conclusion

Transverse sternal plating with 1 or 4 plates significantly improves sternal stability closure in human cadaver model. Adding a single sternal plate to primary closure improves the strength of sternal closure with traditional wiring potentially reducing the risk of sternal dehiscence and could be considered in high risk patients.
Determination of normal values for navicular drop during walking: a new model correcting for foot length and gender
Authors: Nielsen Rasmus G , Rathleff Michael S , Simonsen Ole H , Langberg Henning
Published: May 2009

Background

The navicular drop test is a measure to evaluate the function of the medial longitudinal arch, which is important for examination of patients with overuse injuries. Conflicting results have been found with regard to differences in navicular drop between healthy and injured participants. Normal values have not yet been established as foot length, age, gender, and Body Mass Index (BMI) may influence the navicular drop. The purpose of the study was to investigate the influence of foot length, age, gender, and BMI on the navicular drop during walking.

Methods

Navicular drop was measured with a novel technique (Video Sequence Analysis, VSA) using 2D video. Flat reflective markers were placed on the medial side of the calcaneus, the navicular tuberosity, and the head of the first metatarsal bone. The navicular drop was calculated as the perpendicular distance between the marker on the navicular tuberosity and the line between the markers on calcaneus and first metatarsal head. The distance between the floor and the line in standing position between the markers on calcaneus and first metatarsal were added afterwards.

Results

280 randomly selected participants without any foot problems were analysed during treadmill walking (144 men, 136 women). Foot length had a significant influence on the navicular drop in both men (p < 0.001) and women (p = 0.015), whereas no significant effect was found of age (p = 0.27) or BMI (p = 0.88). Per 10 mm increase in foot length, the navicular drop increased by 0.40 mm for males and 0.31 mm for females. Linear models were created to calculate the navicular drop relative to foot length.

Conclusion

The study demonstrated that the dynamic navicular drop is influenced by foot length and gender. Lack of adjustment for these factors may explain, at least to some extent, the disagreement between previous studies on navicular drop. Future studies should account for differences in these parameters.
Parameter optimization for finishing hard materials with magnetorheological fluid using the penalized multi-response Taguchi method
Authors: Jung B , Jang K-I , Min B-K , Lee S J , Seok J
Published: May 2009

This paper presents a novel penalized multi-response Taguchi method that is used to determine the optimal conditions and parameters for a wheel-type magnetorheological (MR) finishing process that uses sintered iron-carbon nanotube (I-CNT) abrasives. The main goal of this study is to achieve the best compromise, within given boundary constraint conditions, between the maximum material removal rate and the minimum surface roughness. The proposed Taguchi method includes two main parameters, namely the weighting loss factor and the severity factor, that account, respectively, for the response weights and the constraint conditions and that control the optimality direction. The method is applied to the finishing of hard-disk slider surfaces made of Al2O3-TiC, and the effects of the weighting loss and severity factors, along with their significance and relative importance in optimizing the finishing process, are thoroughly examined.
Methodology for draft schedule design of plate rolling process with peening effect considered
Authors: Moon C H , Lee Y
Published: May 2009

We propose an approach for designing a draft schedule applicable to thick plate rolling. In the proposed approach, the peening effect, i.e. thick material is rolled with a small reduction ratio, is considered fully in computing roll force and torque. To determine an initial draft schedule, we calculate material thickness at each pass and total number of passes by taking the smallest of the critical reduction ratios (reduction ratio by maximum reduction increment, reduction ratio assigned in designing a plate mill, reduction ratios by allowable roll force and roll torque). To make a final draft schedule, we then propose two ways (thickness ratio correction (TRC) method and reduction ratio correction (RRC) method) that redistribute reduction ratios predetermined in the initial draft schedule. The proposed approach has been applied to POSCO No. 2 Plate Mill.

Results reveal that the reduction ratios are determined by allowable roll torque if the material being rolled is relatively thick, but reduction ratios are decided by roll force as the material thickness being rolled decreases. It has been found that the thickness ratio correction method is useful when a heavy reduction ratio is necessary in the later part of the rough rolling sequence, and obtaining a uniform microstructure over material thickness during rolling is important. Meanwhile, the reduction ratio correction method is effective if surface defect generation on the material during rolling is a concern.