bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of prematurity, low birthweight and pre-eclampsia in relation to working hours and physical activities: a systematic review
Authors: Bonzini Matteo , Coggon David , Palmer Keith T 
Published: November 2006

Background:Occupational activities are suspected of having an adverse impact on outcomes of pregnancy.Aim:To assess the evidence relating three major adverse outcomes (preterm delivery, low birthweight (LBW) and pre-eclampsia/gestational hypertension) to five common occupational exposures (prolonged working hours, shift work, lifting, standing and heavy physical workload).Methods:A systematic search of Medline and Embase (1966–December 2005) using combinations of keywords and medical subject heading terms was conducted. For each relevant paper, standard details were abstracted that were then used to summarise the design features of studies, to rate their methodological quality (completeness of reporting and potential for important bias or confounding) and to provide estimates of effect. For studies with similar definitions of exposure and outcome, pooled estimates of relative risk (RR) in meta-analysis were calculated.Results:53 reports were identified—35 on preterm delivery, 34 on birth weight and 9 on pre-eclampsia or gestational hypertension. These included 21 cohort investigations. For pre-term delivery, extensive evidence relating to each of the exposures of interest was found. Findings were generally consistent and tended to rule out a more than moderate effect size (RR >1.4). The larger and most complete studies were less positive, and pooled estimates of risk pointed to only modest or null effects. For small-for-gestational age, the position was similar, but the evidence base was more limited. For pre-eclampsia and gestational hypertension, it was too small to allow firm conclusions.Conclusions:The balance of evidence is not sufficiently compelling to justify mandatory restrictions on any of the activities considered in this review. However, given some uncertainties in the evidence base and the apparent absence of important beneficial effects, it may be prudent to advise against long working hours, prolonged standing and heavy physical work, particularly late in pregnancy. Our review identifies several priorities for future investigation.
The Impact of Participative and Directive Leadership on Teachers' Performance: The Intervening Effects of Job Structuring, Decision Domain, and Leader-Member Exchange
Authors: Somech Anit , Wenderow Maayan 
Published: November 2006

Purpose: The contingency model theory suggests that the effects of a leadership style cannot be studied without explicit attention to the given situation. Accordingly, the authors propose a model that allows them to examine simultaneously the relative impact of participative leadership and directive leadership on teachers' performance through the intervening effects of three factors: job structuring (bureaucratic job structuring vs. person-job integration), decision domain (technical vs. managerial), and leader-member exchange (LMX). Method: Data were collected from a survey of 100 teachers and their principals at seven elementary schools in northern Israel. Results: The mixed models analysis shows that although the impact of directive leadership on teachers' performance was contingent in nature, the positive effect of participative leadership on their performance was above and beyond the specific conditions studied. Regarding the impact of directive leadership on teachers' performance, job structuring, decision domain, and LMX served as moderators in the directive leadership–teachers' performance relationship. Implications: These results offer a basis for ongoing conceptual development by helping researchers and practitioners to move from an either/or to a both/and leadership approach. Moreover, these interpretations take direction and participation to be interpersonal processes rather than stable personality traits.
Leadership for Social Justice and Equity: Evaluating a Transformative Framework and Andragogy
Authors: Brown Kathleen M. 
Published: November 2006

Purpose: This study explores the effects of an alternative, transformative andragogy (i.e., the art and science of helping others to learn) designed to be responsive to the challenges of preparing educational leaders committed to social justice and equity. Design: Within the context of preparation programs, the three theoretical perspectives of adult learning theory, transformative learning theory, and critical social theory are interwoven with the three andragogical processes of critical reflection, rational discourse, and policy praxis to form an alternative, transformative framework. Forty graduate students of educational administration (two cohorts of preservice leaders) participated in this study. Quantitative methods are used to assess the possible effects of transformative learning strategies on preservice leaders' attitudes toward issues of diversity in education. Qualitative research methods are then employed to further explore the possible effects of andragogical approaches on preservice leaders' personal beliefs and their reported ability to connect theory to practice. Findings: Findings indicate that participation in transformative learning processes and strategies can increase students' perceived growth in awareness, acknowledgement, and action toward social justice. Implications: The strategies used were created to help future leaders develop as transformative, reflective scholars and practitioners actively engaged in political, emancipatory interests. By participating in a number of assignments requiring the examination of ontological and epistemological assumptions, values and beliefs, context and experience, and competing worldviews, transformation is possible.
Assessing School Achievement Progress: Comparing Alternative Approaches
Authors: Heck Ronald H. 
Published: November 2006

Purpose: Currently under the No Child Left Behind Act, cut scores of successive cohorts of students are used to identify schools that are successful and others that are failing. For many schools, however, this score does not provide an accurate, fair, or comprehensive performance assessment. The focus of this study is to compare three alternative approaches for estimating student progress with respect to their accuracy, equity, and usefulness in making inferences about school effectiveness. Research Design: The study compares achievement estimates compiled across a 4-year period from successive and longitudinal cohorts in a multilevel sample of 123 elementary schools and several thousand students. Findings: First, method effects associated with the designs interact with estimates of school effectiveness. Less than 20% of the schools are similarly identified as meeting performance standards across all three designs investigated. Second, in each approach, contextual indicators (e.g., student composition) dominate in explaining between-school differences in proficiency levels. Third, the longitudinal-cohort approach provides more comprehensive results about performance because of the simultaneous focus on student proficiency and growth. Equity and usefulness are also increased in comparisons of student growth because student composition and context effects are diminished and, conversely, process effects (e.g., academic expectations) are increased in explaining school differences. Conclusions: The comparisons suggest caution in making decisions about schools based on proficiency levels because both method effects and extraneous variables interact with the validity of estimates obtained. Modeling students' growth trajectories, however, can uncover positive school results that are missed in the current proficiency-status approach.
Transplantation of vascular endothelial cells mediates the hematopoietic recovery and survival of lethally irradiated mice
Authors: Chute John P. , Muramoto Garrett G. , Salter Alice B. , Meadows Sarah K. , Rickman Dennis W. , Chen Benny , Himburg Heather A. , Chao Nelson J. 
Published: November 2006

AbstractFlk-1+ endothelial progenitors contribute critically to the definitive onset of hematopoiesis during embryogenesis. Recent studies have suggested that adult sources of endothelial cells also possess hematopoietic activity. In this study, we sought to determine whether transplantation of primary vascular endothelial cells (ECs) could enhance the hematopoietic recovery and survival of irradiated mice. C57Bl6 mice were exposed to sublethal and lethal doses of irradiation and were subsequently given transplants of either primary murine brain–derived ECs (MBECs) or fetal blood-derived ECs (FBECs). Mice that received a transplant with MBECs alone demonstrated accelerated BM cellular recovery, radioprotection of BM c-kit+sca-1−lin− progenitors and enhanced regeneration of c-kit+sca-1+lin− (KSL) stem/progenitor cells following irradiation compared with controls. MBEC transplantation also facilitated the recovery of circulating white blood cell and platelet counts following radiation exposure. Remarkably, 57% of mice that received a transplant with MBECs alone survived long term following 1050 cGy exposure, which was 100% lethal in control mice. FBEC transplantation was also associated with increased survival compared with controls, although these mice did not survive in the long term. These data suggest that reestablishment of endothelial cell activity can improve the hematopoietic recovery and survival of irradiated mice.
Cytokine and integrin stimulation synergize to promote higher levels of GATA-2, c-myb, and CD34 protein in primary human hematopoietic progenitors from bone marrow
Authors: Dao Mo A. , Nolta Jan A. 
Published: November 2006

AbstractWe have previously shown that engagement of the integrins VLA-4 and VLA-5 to the fibronectin fragment CH-296 in combination with cytokines sustained the capacity of cultured human CD34+ cells to undergo hematopoiesis in immunodeficient mice for 7 to 12 months, whereas this capacity was rapidly lost in cells cultured in suspension with the same cytokines. In the current study, we assessed the molecular pathways that might explain the loss of long-term engraftment capacity in cells cultured in suspension. Although the cell cycle profile was similar between cells cultured in suspension versus on fibronectin, levels of cell death were higher in the suspended cultures. While the CDK inhibitors p27Kip1 and p57Kip2 were present at equal levels in cells from both cultures, low levels of p21Cip1 were detectable only in the cytoplasmic compartment of cells cultured in suspension. Cytoplasmic location of p21Cip1 has been linked to monocytic differentiation. The levels of c-myb and GATA-2, transcription factors associated with stem cell maintenance, were higher in cells cultured on fibronectin as compared with suspension. In contrast, the levels of PU.1, which is induced during myeloid differentiation, were higher in cells cultured in suspension. There were no significant differences in surface expression of CD34 on the cells after culture, but total CD34 protein, assessed by immunoblotting, was significantly higher in cells cultured on fibronectin. Our data suggest that, in the presence of cytokines, the engagement of VLA-4 and VLA-5 integrins to the fibronectin fragment CH-296 preserves the expression of specific transcription factors associated with primitive stem cell maintenance. In contrast, a lack of integrin engagement leads to the induction of cellular markers associated with myeloid differentiation.
Src family kinases mediate neutrophil adhesion to adherent platelets
Authors: Evangelista Virgilio , Pamuklar Zehra , Piccoli Antonio , Manarini Stefano , Dell'Elba Giuseppe , Pecce Romina , Martelli Nicola , Federico Lorenzo , Rojas Mauricio , Berton Giorgio , Lowell Clifford A. , Totani Licia , Smyth Susan S. 
Published: November 2006

Abstract
Polymorphonuclear leukocyte (PMN)–platelet interactions at sites of vascular damage contribute to local and systemic inflammation. We sought to determine the role of “outside-in” signaling by Src-family tyrosine kinases (SFKs) in the regulation of αMβ2-integrin–dependent PMN recruitment by activated platelets under (patho)physiologic conditions. Activation-dependent epitopes in β2 integrin were exposed at the contact sites between PMNs and platelets and were abolished by SFK inhibitors. PMNs from αMβ2−/−, hck−/−fgr−/−, and hck−/−fgr−/−lyn−/− mice had an impaired capacity to adhere with activated platelets in suspension. Phosphorylation of Pyk2 accompanied PMN adhesion to platelets and was blocked by inhibition as well as by genetic deletion of αMβ2 integrin and SFKs. A Pyk2 inhibitor reduced platelet-PMN adhesion, indicating that Pyk2 may be a downstream effector of SFKs. Analysis of PMN-platelet interactions under flow revealed that SFK signaling was required for αMβ2-mediated shear-resistant adhesion of PMNs to adherent platelets, but was dispensable for P-selectin–PSGL-1–mediated recruitment and rolling. Finally, SFK activity was required to support PMN accumulation along adherent platelets at the site of vascular injury, in vivo. These results definitely establish a role for SFKs in PMN recruitment by activated platelets and suggest novel targets to disrupt the pathophysiologic consequences of platelet-leukocyte interactions in vascular disease.
MRP8/MRP14 impairs endothelial integrity and induces a caspase-dependent and -independent cell death program
Authors: Viemann Dorothee , Barczyk Katarzyna , Vogl Thomas , Fischer Ute , Sunderkötter Cord , Schulze-Osthoff Klaus , Roth Johannes 
Published: November 2006

AbstractActivated phagocytes express considerable amounts of MRP8 and MRP14, 2 calcium-binding S100 proteins forming stable heterodimers that are specifically secreted at inflammatory sites in many diseases. We previously reported that treatment of human microvascular endothelial cells with purified MRP8/MRP14 leads to loss of endothelial cell contacts. In this study, we demonstrate that MRP8/MRP14 complexes furthermore trigger cell death of endothelial cells after the onset of cell detachment. Morphologic analysis of dying endothelial cells revealed characteristic features of both apoptosis and necrosis. Furthermore, MRP8/MRP14 induced apoptotic caspase-9 and caspase-3 activation, DNA fragmentation, and membrane phosphatidylserine exposure in target cells. These events were independent of death receptor signaling and in part controlled by a mitochondrial pathway. Consistently, overexpression of antiapoptotic Bcl-2 abrogated caspase activation and externalization of phosphatidylserine; however, MRP8/MRP14 still induced plasma membrane damage and even DNA fragmentation. Thus, our results demonstrate that MRP8/MRP14 triggers cell death via caspase-dependent as well as -independent mechanisms. Excessive release of cytotoxic MRP8/MRP14 by activated phagocytes might therefore present an important molecular pathomechanism contributing to endothelial damage during vasculitis and other inflammatory diseases.
End points to establish the efficacy of new agents in the treatment of acute leukemia
Authors: Appelbaum Frederick R. , Rosenblum Daniel , Arceci Robert J. , Carroll William L. , Breitfeld Philip P. , Forman Stephen J. , Larson Richard A. , Lee Stephanie J. , Murphy Sharon B. , O'Brien Susan , Radich Jerald , Scher Nancy S. , Smith Franklin O. , Stone Richard M. , Tallman Martin S. 
Published: November 2006

AbstractFederal regulations provide 2 pathways for approval of new agents for the treatment of acute leukemia, regular and accelerated approval. Regular approval requires evidence of clinical benefit, which is generally defined as either prolongation of life or improved quality of life, or an effect on an end point established as a surrogate for clinical benefit. Accelerated approval can be obtained based on demonstration of an effect on a surrogate measure “reasonably likely” to predict clinical benefit, but requires demonstration of clinical benefit after approval as well. The acute leukemias are a heterogeneous and relatively uncommon group of diseases. The design and execution of prospective randomized clinical trials demonstrating prolongation of life or improved quality of life for patients with these disorders can be difficult and costly and require lengthy follow-up. Thus, the development of novel trial design and inclusion of validated surrogate markers for clinical benefit are needed. To explore some of the issues pertinent to the choice of end points for drug approval in acute leukemia, the Food and Drug Administration invited the American Society of Hematology to participate in the organization and conduct of a joint workshop. In this report, we present the results of that effort.
Structure-based discovery of inhibitors of the YycG histidine kinase: New chemical leads to combat Staphylococcus epidermidis infections
Authors: Qin Zhiqiang , Zhang Jian , Xu Bin , Chen Lili , Wu Yang , Yang Xiaomei , Shen Xu , Molin Soeren , Danchin Antoine , Jiang Hualiang , Qu Di 
Published: November 2006

Abstract

Background
Coagulase-negative Staphylococcus epidermidis has become a major frequent cause of infections in relation to the use of implanted medical devices. The pathogenicity of S. epidermidis has been attributed to its capacity to form biofilms on surfaces of medical devices, which greatly increases its resistance to many conventional antibiotics and often results in chronic infection. It has an urgent need to design novel antibiotics against staphylococci infections, especially those can kill cells embedded in biofilm.

Results
In this report, a series of novel inhibitors of the histidine kinase (HK) YycG protein of S. epidermidis were discovered first using structure-based virtual screening (SBVS) from a small molecular lead-compound library, followed by experimental validation. Of the 76 candidates derived by SBVS targeting of the homolog model of the YycG HATPase_c domain of S. epidermidis, seven compounds displayed significant activity in inhibiting S. epidermidis growth. Furthermore, five of them displayed bactericidal effects on both planktonic and biofilm cells of S. epidermidis. Except for one, the compounds were found to bind to the YycG protein and to inhibit its auto-phosphorylation in vitro, indicating that they are potential inhibitors of the YycG/YycF two-component system (TCS), which is essential in S. epidermidis. Importantly, all these compounds did not affect the stability of mammalian cells nor hemolytic activities at the concentrations used in our study.

Conclusion
These novel inhibitors of YycG histidine kinase thus are of potential value as leads for developing new antibiotics against infecting staphylococci. The structure-based virtual screening (SBVS) technology can be widely used in screening potential inhibitors of other bacterial TCSs, since it is more rapid and efficacious than traditional screening technology.
Antimicrobial effects of liquid anesthetic isoflurane on Candida albicans
Authors: Barodka Viachaslau M , Acheampong Edward , Powell Garry , Lobach Ludmila , Logan David A , Parveen Zahida , Armstead Valerie , Mukhtar Muhammad 
Published: November 2006

Abstract

Candida albicans is a dimorphic fungus that can grow in yeast morphology or hyphal form depending on the surrounding environment. This ubiquitous fungus is present in skin and mucus membranes as a potential pathogen that under opportunistic conditions causes a series of systemic and superficial infections known as candidiasis, moniliasis or simply candidiasis. There has been a steady increase in the prevalence of candidiasis that is expressed in more virulent forms of infection. Although candidiasis is commonly manifested as mucocutaneous disease, life-threatening systemic invasion by this fungus can occur in every part of the body. The severity of candidal infections is associated with its morphological shift such that the hyphal morphology of the fungus is most invasive. Of importance, aberrant multiplication of Candida yeast is also associated with the pathogenesis of certain mucosal diseases. In this study, we assessed the anti-candidal activity of the volatile anesthetic isoflurane in liquid form in comparison with the anti-fungal agent amphotericin B in an in vitro culture system. Exposure of C. albicans to isoflurane (0.3% volume/volume and above) inhibited multiplication of yeast as well as formation of hyphae. These data suggest development of potential topical application of isoflurane for controlling a series of cutaneous and genital infections associated with this fungus. Elucidiation of the mechanism by which isoflurane effects fungal growth could offer therapeutic potential for certain systemic fungal infections.
1α,25(OH)2D3-Induced Transrepression by Vitamin D Receptor through E-Box-Type Elements in the Human Parathyroid Hormone Gene Promoter
Authors: Kim Mi-sun , Fujiki Ryoji , Murayama Akiko , Kitagawa Hirochika , Yamaoka Kazuyoshi , Yamamoto Yoko , Mihara Masatomo , Takeyama Ken-ichi , Kato Shigeaki 
Published: November 2006

AbstractAlthough transactivation by the liganded vitamin D receptor (VDR) is well described at the molecular level, the precise molecular mechanism of negative regulation by the liganded VDR remains to be elucidated. We have previously reported a novel class of negative vitamin D response element (nVDRE) called 1αnVDRE in the human 25(OH)D31α-hydroxylase [1α(OH)ase] gene by 1α,25(OH)2D3-bound VDR. This element was composed of two E-box-type motifs that bound to VDIR for transactivation, which was attenuated by liganded VDR. Here, we explore the possible functions of VDIR and E-box motifs in the human (h) PTH and hPTHrP gene promoters. Functional mapping of the hPTH and hPTHrP promoters identified E-box-type elements acting as nVDREs in both the hPTH promoter (hPTHnVDRE; −87 to −60 bp) and in the hPTHrP promoter (hPTHrPnVDRE; −850 to −600 bp; −463 to −104 bp) in a mouse renal tubule cell line. The hPTHnVDRE alone was enough to direct ligand-induced transrepression mediated through VDR/retinoid X receptor and VDIR. Direct DNA binding of hPTHnVDRE to VDIR, but not VDR/retinoid X receptor, was observed and ligand-induced transrepression was coupled with recruitment of VDR and histone deacetylase 2 (HDAC2) to the hPTH promoter. These results suggest that negative regulation of the hPTH gene by liganded VDR is mediated by VDIR directly binding to the E-box-type nVDRE at the promoter, together with recruitment of an HDAC corepressor for ligand-induced transrepression.
Methylmercury Measurement in Whole Blood by Isotope-Dilution GC-ICPMS with 2 Sample Preparation Methods
Authors: Baxter Douglas C , Rodushkin Ilia , Engström Emma , Klockare Dennis , Waara Hans 
Published: November 2006

Abstract
Background: Despite its known toxicity, methylmercury is rarely measured directly in clinical studies; instead, conclusions are based on total mercury measurements. We have developed isotope–dilution-based methods for methylmercury-specific analysis of whole blood by coupled gas chromatography–inductively coupled plasma mass spectrometry (GC-ICPMS).
Methods: We analyzed animal and human blood samples after alkaline digestion or extraction of methylmercury into dichloromethane and back extraction into water. Methylmercury was converted to the volatile ethyl derivative, purged, and trapped on a solid-phase collection medium, and then introduced into the GC-ICPMS system.
Results: Limits of quantification were 0.4 and 0.03 μg/L at a signal-to-noise ratio of 10 with the alkaline digestion and extraction methods, respectively. Extraction met our selected acceptable total error criterion, with an SD of 0.58 μg/L at the critical maternal blood concentration of 5.8 μg/L. Results obtained with alkaline digestion indicated the need for improved random analytical uncertainty, which was achieved by increasing the enrichment of the isotope dilution. For 37 blood samples, the mean (SD) proportion of total mercury present as methylmercury was 60 (27)%, range 6%–100%.
Conclusions: The combination of extraction and isotope-dilution GC-ICPMS meets the requirements for use as a reference method for measuring methylmercury in whole blood.