bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection and Diagnosis of Person Misfit From Patterns of Summed Polytomous Item Scores
Authors: Emons Wilco H. M.
Published: October 2009

For valid decision making, it is essential to both the person being measured and the person or organization that is having the person measured that the observed scores adequately represent the underlying trait. This study deals with person-fit analysis of polytomous item scores to detect unusual patterns of sum scores on subsets of items. This approach has the advantage that it allows for a diagnostic approach in which specific hypotheses of person misfit can be tested. In a simulation study, the false-positive and detection rates have been investigated under varying test and item characteristics and different types and levels of aberrant response behavior. The performance of the sum-score—based approach is compared with the perforance of the lPz person-fit measure. The simulations show that the person-fit analysis based on sum-score patterns is useful and performs best for detecting aberrant response behavior that manifests itself locally in the pattern, such as careless responding to reverse-worded tems. Statistic lPz performs better for detecting aberrant response behavior that affects the responses globally, such as a tendency to choose extreme response options. The person-fit measures discussed are illustrated using real data from the Neuroticism—Extraversion—Openness Personality Inventory—Revised.
Calcium and Phosphate Compatibility in Low‐Osmolarity Parenteral Nutrition Admixtures Intended for Peripheral Vein Administration
Authors: Joy Julie , Silvestri Anthony P. , Franke Rolf , Bistrian Bruce R. , Nehne Jörg , Newton David W. , Driscoll David F.
Published: October 2009

Background: Precipitation of calcium (Ca) and phosphate (P) salts can lead to potentially lethal outcomes, especially in low‐osmolarity parenteral nutrition (LO‐PN) formulations. Three concentrations of amino acids (AA) and 2 concentrations of calcium gluconate and sodium phosphate injections on the compatibility of Ca and P in LO‐PN admixtures were studied. Methods: Final AA concentrations of 1%, 2%, or 3% (n = 3) and 5% glucose (G) were prepared with either 2.5 or 5 mmol/L (5 or 10 mEq) of Ca (n = 2) and 15 or 30 mmol/L of P (n = 2) for a total of 12 base (3 × 2× 2) formulations. Triplicate bags of each were analyzed for subvisible micro‐precipitates using the light obscuration (or extinction) method for particle counts per milliliter (PC) in the size range of 1.8‐50 μm at 7 time intervals over 48 hours stored at 30°C ± 0.2°C. Visual evaluation was performed using a high‐intensity lamp against a black background for detection of macro‐precipitates. The pH of all 36 admixtures was measured at 0 and 48 hours. Any precipitated material was isolated and characterized by polarized light microscopy and infrared spectroscopy. Results: Of the 12 base LO‐PN formulations tested, those containing 1% and 2% AA with 5 mmol/L of Ca and 30 mmol/L of P showed significant increases in PC, and some resulted in visible dibasic calcium phosphate precipitation. Analyses of variance based on concentrations of AA, Ca, P, and time were highly significant independent variables for increases in the PC of potentially embolic particles, that is, sizes >5 μm (P < .0001). The lowest concentrations of Ca and P, 2.5 and 15 mmol/L, respectively, had significantly lower PC (P < .05) for all sizes compared with the other Ca and P combinations. Conclusions: LO‐PN admixtures (AA ≤ 3%; G = 5%) should not contain more than 2.5 mmol/L of Ca from calcium gluconate injection and no more than 15 mmol/L of P from potassium or sodium phosphates injection.
Sibling-Implemented Intervention for Skill Development With Children With Disabilities
Authors: Kim Taeyoung , Horn Eva
Published: October 2009

The research synthesis presented here reviewed the currently available evidence on the effectiveness of sibling-implemented interventions for their siblings with disabilities. The search for appropriate research literature spanned from 1975 to 2008 and resulted in a total of eight studies that met the inclusion criteria. All eight studies in this synthesis employed single-case design as the primary research methodology. The analysis of the eight studies is summarized into (a) experimental design and participants, (b) intervention features, (c) measurement procedures, and (d) findings. Taken together, the outcomes of this research synthesis provide support for the effectiveness of sibling-implemented intervention for children with disabilities. Furthermore, implications for further research are discussed including taking into account specific siblings’ characteristics (e.g., socialization, intellectual ability) and ensuring that future studies sufficiently address generalization and maintenance of intervention effect and collect rigorous data on implementation fidelity.
Shallow Medial Tibial Plateau and Steep Medial and Lateral Tibial Slopes: New Risk Factors for Anterior Cruciate Ligament Injuries
Authors: Hashemi Javad , Chandrashekar Naveen , Mansouri Hossein , Gill Brian , Slauterbeck James R. , Schutt Robert C. , Dabezies Eugene , Beynnon Bruce D.
Published: October 2009

Background

The geometry of the tibial plateau has been largely ignored as a source of possible risk factors for anterior cruciate ligament injury. Discovering the anterior cruciate ligament injury risk factors associated with the tibial plateau may lead to delineation of the existing sex-based disparity in anterior cruciate ligament injuries and help develop strategies for the prevention of anterior cruciate ligament injuries regardless of gender.

Hypothesis

Individuals with a shallower medial tibial depth of concavity, while having increased posteriorly directed slope of their tibial plateau, are at increased risk of suffering an anterior cruciate ligament injury compared with those with decreased posterior slope and increased medial tibial depth. Furthermore, these relationships are different between men and women.

Study Design

Case-control study (prevalence); Level of evidence, 3.

Methods

The medial, lateral, and coronal tibial plateau slopes as well as the medial tibial depth of concavity in 55 uninjured controls (33 women and 22 men) and 49 anterior cruciate ligament—injured cases (27 women and 22 men) were measured using magnetic resonance images. First, a preliminary t test was performed to establish any existing differences between groups. Next, a logistic regression model was developed to determine the probability of anterior cruciate ligament injury in an individual based on the measured covariates.

Results

The female anterior cruciate ligament—injured cases had increased lateral tibial slope (P = .03) and shallower medial tibial depth (P = .0003) compared with the uninjured controls, while male cases had increased lateral and medial tibial slope (P = .02) and shallower medial tibial depth (P = .0004) compared with controls. The logistic regression analysis and odds ratio estimates showed that medial tibial depth is an important risk factor (odds ratio = 3.03 per 1 mm decrease in its value), followed by lateral tibial slope (odds ratio = 1.17 per 1° increase in its value) in all participants. The medial tibial slope (odds ratio = 1.18 per 1° increase in its value) was a risk factor only in men.

Conclusion

A combination of increased posterior-directed tibial plateau slope and shallow medial tibial plateau depth could be a major risk factor in anterior cruciate ligament injury susceptibility regardless of gender. Different injury risk models may be needed for men and women as other key risk factors are identified.
Zonal Chondrocyte Subpopulations Reacquire Zone-Specific Characteristics during in Vitro Redifferentiation
Authors: Schuurman Wouter , Gawlitta Debby , Klein Travis J. , ten Hoope Werner , van Rijen Mattie H. P. , Dhert Wouter J. A. , van Weeren P. René , Malda Jos
Published: October 2009

Background

If chondrocytes from the superficial, middle, and deep zones of articular cartilage could maintain or regain their characteristic properties during in vitro culture, it would be feasible to create constructs comprising these distinctive zones.

Hypothesis

Zone-specific characteristics of zonal cell populations will disappear during 2-dimensional expansion but will reappear after 3-dimensional redifferentiation, independent of the culture technique used (alginate beads versus pellet culture).

Study Design

Controlled laboratory study.

Methods

Equine articular chondrocytes from the 3 zones were expanded in monolayer culture (8 donors) and subsequently redifferentiated in pellet and alginate bead cultures for up to 4 weeks. Glycosaminoglycans and DNA were quantified, along with immunohistochemical assessment of the expression of various zonal markers, including cartilage oligomeric protein (marking cells from the deeper zones) and clusterin (specifically expressed by superficial chondrocytes).

Results

Cell yield varied between zones, but proliferation rates did not show significant differences. Expression of all evaluated zonal markers was lost during expansion. Compared to the alginate bead cultures, pellet cultures showed a higher amount of glycosaminoglycans produced per DNA after redifferentiation. In contrast to cells in pellet cultures, cells in alginate beads regained zonal differences, as evidenced by zone-specific reappearance of cartilage oligomeric protein and clusterin, as well as significantly higher glycosaminoglycans production by cells from the deep zone compared to the superficial zone.

Conclusion

Chondrocytes isolated from the 3 zones of equine cartilage can restore their zone-specific matrix expression when cultured in alginate after in vitro expansion.

Clinical Relevance

Appreciation of the zonal differences can lead to important advances in cartilage tissue engineering. Findings support the use of hydrogels such as alginate for engineering zonal cartilage constructs.
Acute Hemodynamic Effects of Recruitment Maneuvers in Patients With Acute Respiratory Distress Syndrome
Authors: Kwang Joo Park  , Yoon Jung Oh  , Hyuk Jae Chang  , Seung Soo Sheen  , Choi Junghyun , Keu Sung Lee  , Joo Hun Park  , Sung Chul Hwang
Published: October 2009

Background: The recruitment maneuver (RM) in acute respiratory distress syndrome (ARDS) can cause hemodynamic derangement. We evaluated circulatory and cardiac changes during RMs.

Methods: We performed sustained inflation (SI) with a pressure of 40 cm H2O for 30 seconds as an RM on 22 patients with ARDS. Blood pressure (BP) and heart rate were recorded immediately before, every 10 seconds during, and 30 seconds after the RM. Ventricular dimensions were obtained simultaneously using M-mode echocardiography, and tissue Doppler imaging was performed on the left ventricular wall.

Results: Mean, systolic, and diastolic BP decreased at 20 and 30 seconds during 30-second RMs (mean BP: 92 ± 12 at baseline to 83 ± 18 mm Hg at the end of the RM, P < .05) and subsequently recovered. Heart rate decreased at 10 and 20 seconds during the RM, and tended to increase afterward. Both ventricular dimensions decreased significantly during the RM. The left ventricular ejection fraction and peak velocity of the left ventricle during systole remained stable. The fractional changes in mean BP and left ventricular end-diastolic dimension during the RMs were correlated significantly with each other (rs = 0.59). Static compliance of the respiratory system (Crs) was lower in patients with mean BP change ≥15% than in patients in whom the change was <15% (P < .05).

Conclusions: A transient decrease in mean BP was observed during the RM, and its degree was correlated with the preload decrease, while cardiac contractility was maintained.
Education Policy as a Practice of Power
Authors: Levinson Bradley A. U. , Sutton Margaret , Winstead Teresa
Published: October 2009

This article outlines some theoretical and methodological parameters of a critical practice approach to policy. The article discusses the origins of this approach, how it can be uniquely adapted to educational analysis, and why it matters—not only for scholarly interpretation but also for the democratization of policy processes as well. Key to the exposition is the concept of appropriation as a form of creative interpretive practice necessarily engaged in by different people involved in the policy process. Another crucial distinction is made between authorized policy and unauthorized or informal policy; it is argued that when nonauthorized policy actors appropriate policy they are in effect often making new policy in situated locales and communities of practice.
Are School Uniforms a Good Fit?
Authors: Yeung Ryan
Published: October 2009

One of the most common proposals put forth for reform of the American system of education is to require school uniforms. Proponents argue that uniforms can make schools safer and also improve school attendance and increase student achievement. Opponents contend that uniforms have not been proven to work and may be an infringement on the freedom of speech of young people. Within an econometric framework, this study examines the effect of school uniforms on student achievement. It tackles methodological challenges through the use of a value-added functional form and the use of multiple data sets. The results do not suggest any significant association between school uniform policies and achievement. Although the results do not definitely support or reject either side of the uniform argument, they do strongly intimate that uniforms are not the solution to all of American education’s ills.
Astaxanthin Reduces Oxidative Stress, but not Aortic Damage in Atherosclerotic Rabbits
Authors: Augusti Paula R. , Conterato Greicy M. M. , Somacal Sabrina , Sobieski Rocheli , Quatrin Andréia , Maurer Luana , Rocha Marta P. , Denardin Ione T. , Emanuelli Tatiana
Published: October 2009

We evaluated whether carotenoid astaxanthin (ASX) could prevent oxidative and atherosclerotic damage in rabbits. Rabbits received regular chow (control) or an atherogenic diet (1% cholesterol) alone or supplemented with 50, 100, and 500 mg% ASX for 60 days (n = 5-9 per group). The atherogenic diet increased the serum cholesterol levels and the ratio of the intima/media area in the aortic arch. These changes were not prevented by ASX. Atherosclerotic rabbits showed increased aortic lipid peroxidation and nonprotein thiol group (NPSH) levels along with inhibition of glutathione peroxidase (GSH-Px). All ASX doses attenuated lipid peroxidation and the increase in NPSH but not the inhibition of GSH-Px. Aortic superoxide dismutase (SOD), catalase (CAT), and thioredoxin reductase (TrxR) activities were enhanced in atherosclerotic rabbits. Although all ASX doses prevented the increase in SOD activity, only 100 and 500 mg% ASX prevented the increase in CAT activity. Furthermore, these same doses partially prevented the increase in TrxR activity, while 50 mg% ASX completely prevented the effects of the atherogenic diet on this enzyme. However, ASX did not attenuate the hypercholesterolemia or the atherosclerotic lesions caused by the atherogenic diet at any of the doses evaluated. Our results indicate that although ASX did not prevent hypercholesterolemia or atherosclerotic lesions, it could play a beneficial role by preventing lipid peroxidation and changes in antioxidant enzyme activities.
Strengthening Sociological Perspectives on Organizations and the Environment
Authors: Shwom Rachael
Published: October 2009

Environmental and organizational sociologists have engaged with the growing interdisciplinary study of formal organizations and their natural environment to varying extents, but to date there has been little interaction between the two sociological subdisciplines. Environmental sociology has developed strong understandings of human—environment interactions, how to study them, and political economic systems of environmental destruction and improvement. Meanwhile, organizational sociology provides insights on internal and external drivers of governmental agency, business, and social movement organizational decision making. In an effort to strengthen our sociological understandings of organizational and interorganizational processes that contribute to environmental harm and improvement, this article identifies five synthetic propositions that emerge from these bodies of knowledge: (a) no organization is an island—socially or ecologically, (b) environmental claims require environmental evidence, (c) corporate environmental actions vary and are context dependent, (d) organizational cooperation and cooptation are two sides of the same coin, and (e) cumulative environmental impacts of organizational change are constrained by system tendencies.
Summary of the IESP White Papers
Authors: Mohr Bernd
Published: October 2009

As part of the planning and development process for the IESP workshops, we asked participants to prepare white papers on various topics. We have grouped and summarized the content of the white papers that were contributed here. The list of the white papers relevant to a given group is given at the end of the summary for that group.
Programmability Issues
Authors: Chapman Barbara , Labarta Jesús , Sarkar Vivek , Sato Mitsuhisa
Published: October 2009

Programming models are at the very center of our effort to address the exascale challenge. They are the key interface that will allow the separation of the programmers’ concerns from those of system designers, potentially at different levels of granularity. Any such model must meet the extensive needs of application developers and be supported by the entire software stack. Considerable research is needed to define and implement the programming and execution models for such systems. Whereas evolutionary approaches may best support the migration of existing application software, revolutionary models may be best suited to providing extreme-scale performance for new applications on emerging architectures. Both approaches should be explored.
The Biggest Need: a New Model of Computation
Authors: Sterling Thomas
Published: October 2009

The development of HPC systems capable of exascale performance will demand innovations in hardware architecture and system software as well as programming models and methods. The combination of a vast increase in scale of such systems combined with the emergence of heterogeneous multicore structures is forcing future systems to be organized and operate on principles very different from the conventional practices of the last two decades. The biggest need for achieving exascale computing is the development of a new model of computation that will provide the new paradigm exploiting the opportunities and addressing the challenges of the emerging technologies and advanced architectures that together will comprise future exascale systems. This brief paper discusses the need for a new model of computation and the properties such a model should embody.
On the Importance of End-to-End Application Performance Monitoring and Workload Analysis at the Exascale
Authors: Skinner David , Choudary Alok
Published: October 2009

This paper sets out to examine the future of performance monitoring on exascale HPC systems. In particular we put forth the idea that such machines will be sufficiently complex that performance monitoring of individual applications and the workload as a whole will change from being a beneficial option to being a necessity. This complexity arises from the number of components and concurrencies expected for such systems. We see the need for a shift from performance monitoring being a useful add-on toward it being a core requirement for basic operation and suggest some first steps toward meeting that need.
On the Need for a Consortium of Capability Centers
Authors: Gropp William , Snir Marc
Published: October 2009

Users of high-performance computing systems face many challenges, particularly as they design and develop their software to run at multiple facilities. This can lead to a “greatest common denominator” strategy that slows innovation and the adoption of newer techniques. In addition, these systems typically push the limits — leading to problems with reliability and functionality of the system and software. We propose a consortium of HPC centers to collaborate on raising both the capability and the quality of the software for HPC systems.
Developing a High-Performance Computing/Numerical Analysis Roadmap
Authors: Trefethen Anne , Higham Nick , Duff Iain , Coveney Peter
Published: October 2009

A roadmap activity in the UK has leveraged US and European efforts for identifying the challenges and barriers in the development of high-performance computing (HPC) algorithms and software. The activity has identified the Grand Challenge to provide:

1. Algorithms and software that application developers can reuse in the form of high-quality, high performance, sustained software components, libraries and modules

2. A community environment that allows the sharing of software, communication of interdisciplinary knowledge and the development of appropriate skills.

Through a series of workshops and discussions with UK HPC application groups and numerical analysts, five areas of challenge have emerged.
The Silent and the Silenced in Organizational Knowing and Learning
Authors: Blackman Deborah , Sadler-Smith Eugene
Published: October 2009

Research on silence within organizations and learning is sparse. This article is concerned with exploring the concept of silence in organizational settings, delineating its various forms (silent and silenced) and critically examining the relevance of these various manifestations for management and organizational learning. Following a brief review of the concept of the Polanyian notion of tacitness and how it relates to our conceptualization of silence, we offer a taxonomy of silence comprised of several ways of knowing (tacit, intuitive, insightful and pre-conscious) and voice (repressed, withheld and suppressed). The theoretical and practical implications of the taxonomy for management education, training and development are discussed.
Practice? It’s a Matter of Taste!
Authors: Gherardi Silvia
Published: October 2009

This article aims to enhance our understanding of how practice is socially sustained, learnt and constantly refined by arguing that practice is much more than a set of activities—it involves, beside instrumental and ethical judgements, taste and appraisal. Taste is a sense of what is aesthetically fitting within a community of practitioners—a preference for ‘the way we do things together’. Taste is based on subjective attachment to the object of practice and is learnt and taught as part of becoming a practitioner; it is performed as a collective, situated activity within a practice. The elaboration of taste and the refining of practice within a community involves taste-making, which is based on ‘sensible knowledge’ and the continual negotiation of aesthetic categories. The article examines how in a variety of practices, taste-making occurs through three processes: sharing a vocabulary for appraisal; crafting identities within epistemic communities; and refining performances.
The Effect of Multisensory Stimulation on Persons Residing in an Extended Care Facility
Authors: Ward-Smith Peggy , Llanque Sarah M. , Curran Denise
Published: October 2009

Background: Non-pharmacological interventions, such as multisensory stimulation environments (MSSE), have demonstrated the ability to reduce inappropriate behavior among individuals with Alzheimer’s disease. Methods: In this study, we compared the incidences of problematic behavior among individuals with Alzheimer’s disease residing in a long-term care facility who were and were not exposed to an MSSE. Retrospective data were obtained using the Psychotic Behavior Assessment Record (PBAR), mandated by Medicare to be used when antipsychotic medications are administered. Psychotic Behavior Assessment Record data were collected using the first and sixth month of admission for residents after appropriate consent was secured. Results: Documented disruptive behavior included pacing, exit-seeking activities, hitting, yelling, and aggressive talking. The use of the MSSE resulted in a decrease in the number of incidences of disruptive behavior, but not the behaviors present. Conclusion: The use of MSSE, as a non-pharmacological intervention, demonstrates the ability to decrease the number of incidences of disruptive or problematic behavior. The use of these interventions, where feasible, should be considered prior to the use of pharmacological methods.
A Combined Endovascular and Open ‘‘Reverse Hybrid’’ Technique for Repair of Complex Juxtarenal Inflammatory Aortic Aneurysms
Authors: Rigberg David , Jimenez Juan Carlos , Lawrence Peter , Gelabert Hugh
Published: October 2009

Inflammatory abdominal aortic aneurysms (IAAA) can present significant challenges to surgeons, especially in the juxtarenal location where they may not be amenable to endovascular repair. The dense, inflammatory component of these lesions can encase adjacent structures including the duodenum, ureters, and inferior vena cava putting them at risk for injury during open exposure. We report a novel ‘‘reverse hybrid’’ technique using a combined endovascular and open approach for repair of large, juxtarenal IAAA’s.
Using a Prescreening Rubric for All-State Violin Selection: Influences of Performance and Teaching Experience
Authors: Geringer John M. , Allen Michael L. , MacLeod Rebecca B. , Scott Laurie
Published: October 2009

Performance assessment is an integral part of young musicians’ development. Students enrolled in music programs frequently participate in adjudication festivals and many audition for select ensembles. Outcomes of such events are deemed consequential among all concerned: students, parents, teachers, and administrators. Furthermore, the number of all-state applicants for some individual instruments in many states exceeds 100 and in some states approaches or exceeds 200. This is an inordinate number of recordings or live auditions for individuals or judging panels to evaluate. It seems paramount to utilize an efficient yet fair and accurate audition process to assess large numbers of performances in a short period of time. To explore ways of addressing this issue, the authors designed a prescreening rubric with the goal of reducing the number of full-length recordings heard by judges to a more manageable number. The authors then compared ratings of listeners who used the rubric and heard only the étude portion of the audition to scores of trained and experienced judges who heard the entire audition.
The Effects of Band Labels on Evaluators’ Judgments of Musical Performance
Authors: Silvey Brian A.
Published: October 2009

This study investigates the effects of band labels on evaluators’ judgments of musical performance. High school concert band members ( n = 72), wind ensemble members ( n = 77), and band directors ( n = 8) were randomly assigned to a band label or no label group. Only the band label group was given evaluation forms that specified the group playing the excerpt (“Wind Ensemble” or “Concert Band”). Participants evaluated 12 excerpts and were not made aware that 6 excerpts had actually been repeated twice under varying labels. A two-factor ANOVA showed two significant interactions between label and excerpt presentation order among concert band evaluators in the band label group.
The mouse mutation “thrombocytopenia and cardiomyopathy” (trac) disrupts Abcg5: a spontaneous single gene model for human hereditary phytosterolemia/sitosterolemia
Authors: Chase Thomas H. , Lyons Bonnie L. , Bronson Roderick T. , Foreman Oded , Donahue Leah Rae , Burzenski Lisa M. , Gott Bruce , Lane Priscilla , Harris Belinda , Ceglarek Uta , Thiery Joachim , Wittenburg Henning , Thon Jonathan N. , Italiano Joseph E. , Johnson Kenneth R. , Shultz Leonard D.
Published: October 2009

The spontaneous mouse mutation “thrombocytopenia and cardiomyopathy” (trac) causes macrothrombocytopenia, prolonged bleeding times, anemia, leukopenia, infertility, cardiomyopathy, and shortened life span. Homozygotes show a 20-fold decrease in platelet numbers and a 3-fold increase in platelet size with structural alterations and functional impairments in activation and aggregation. Megakaryocytes in trac/trac mice are present in increased numbers, have poorly developed demarcation membrane systems, and have decreased polyploidy. The thrombocytopenia is not intrinsic to defects at the level of hematopoietic progenitor cells but is associated with a microenvironmental abnormality. The trac mutation maps to mouse chromosome 17, syntenic with human chromosome 2p21-22. A G to A mutation in exon 10 of the adenosine triphosphate (ATP)–binding cassette subfamily G, member 5 (Abcg5) gene, alters a tryptophan codon (UGG) to a premature stop codon (UAG). Crosses with mice doubly transgenic for the human ABCG5 and ABCG8 genes rescued platelet counts and volumes. ABCG5 and ABCG8 form a functional complex that limits dietary phytosterol accumulation. Phytosterolemia in trac/trac mice confirmed a functional defect in the ABCG5/ABCG8 transport system. The trac mutation provides a new clinically significant animal model for human phytosterolemia and provides a new means for studying the role of phytosterols in hematologic diseases and testing therapeutic interventions.
AML1/RUNX1 point mutation possibly promotes leukemic transformation in myeloproliferative neoplasms
Authors: Ding Ye , Harada Yuka , Imagawa Jun , Kimura Akiro , Harada Hironori
Published: October 2009

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by proliferation of one or more myeloid cell lineages. Some patients exhibit leukemic transformation (LT) by unknown mechanisms, and chemotherapy may increase the risk of LT. To clarify the molecular mechanisms of LT, gene alterations involved in LT from patients in the chronic phase (CP) of MPNs were identified. Among 18 patients who progressed to leukemia, AML1/RUNX1 mutations were detected in 5 patients at the LT but in none at the CP. To investigate the leukemogenic effect of AML1/RUNX1 mutants, the AML1D171N mutant was transduced into CD34+ cells from patients in the CP of MPNs. The D171N transduction resulted in proliferation of immature myeloid cells, enhanced self-renewal capacity, and proliferation of primitive progenitors. Taken together, these results indicate that AML1/RUNX1 point mutations may have a leukemogenic potential in MPN stem cells, and they may promote leukemic transformation in MPN.
International consensus report on the investigation and management of primary immune thrombocytopenia
Authors: Provan Drew , Stasi Roberto , Newland Adrian C. , Blanchette Victor S. , Bolton-Maggs Paula , Bussel James B. , Chong Beng H. , Cines Douglas B. , Gernsheimer Terry B. , Godeau Bertrand , Grainger John , Greer Ian , Hunt Beverley J. , Imbach Paul A. , Lyons Gordon , McMillan Robert , Rodeghiero Francesco , Sanz Miguel A. , Tarantino Michael , Watson Shirley , Young Joan , Kuter David J.
Published: October 2009

Previously published guidelines for the diagnosis and management of primary immune thrombocytopenia (ITP) require updating largely due to the introduction of new classes of therapeutic agents, and a greater understanding of the disease pathophysiology. However, treatment-related decisions still remain principally dependent on clinical expertise or patient preference rather than high-quality clinical trial evidence. This consensus document aims to report on new data and provide consensus-based recommendations relating to diagnosis and treatment of ITP in adults, in children, and during pregnancy. The inclusion of summary tables within this document, supported by information tables in the online appendices, is intended to aid in clinical decision making.
Using a water-immiscible ionic liquid to improve asymmetric reduction of 4-(trimethylsilyl)-3-butyn-2-one catalyzed by immobilized Candida parapsilosis CCTCC M203011 cells
Authors: Lou Wen-Yong , Chen Lei , Zhang Bo-Bo , Smith Thomas J , Zong Min-Hua
Published: October 2009

Background

Whole cells are usually employed for biocatalytic reduction reactions to ensure efficient coenzyme regeneration and to avoid problems with enzyme purification and stability. The efficiency of whole cell-catalyzed bioreduction is frequently restricted by pronounced toxicity of substrate and/or product to the microbial cells and in many instances the use of two-phase reaction systems can solve such problems. Therefore, we developed new, biphasic reaction systems with biocompatible water-immiscible ionic liquids (ILs) as alternatives to conventional organic solvents, in order to improve the asymmetric reduction of 4-(trimethylsilyl)-3-butyn-2-one (TMSB) to (S)-4-(trimethylsilyl)-3-butyn-2-ol {(S)-TMSBOL}, a key intermediate for synthesis of 5-lipoxygenase inhibitors, using immobilized Candida parapsilosis CCTCC M203011 cells as the biocatalyst.

Results

Various ILs exerted significant but different effects on the bioreduction. Of all the tested water-immiscible ILs, the best results were observed with 1-butyl-3-methylimidazolium hexafluorophosphate (C4MIM·PF6), which exhibited not only good biocompatibility with the cells but also excellent solvent properties for the toxic substrate and product, thus markedly improving the efficiency of the bioreduction and the operational stability of the cells as compared to the IL-free aqueous system. 2-Propanol was shown to be the most suitable co-substrate for coenzyme regeneration, and it was found that the optimum volume ratio of buffer to C4MIM·PF6, substrate concentration, buffer pH, 2-propanol concentration and reaction temperature were 4/1 (v/v), 24 mM, 5.5, 130 mM and 30°C, respectively. Under these optimized conditions, the maximum yield and the product e.e. wer 97.7% and >99%, respectively, which are much higher than the corresponding values previously reported. The efficient whole-cell biocatalytic process was shown to be feasible on a 250-mL scale.

Conclusion

The whole cell-catalyzed asymmetric reduction of TMSB to (S)-TMSBOL can be substantially improved by using a C4MIM·PF6/buffer biphasic system instead of a single-phase aqueous system and the resulting biocatalytic process appears to be effective and competitive on a preparative scale.
Canonical Wnt signaling is antagonized by noncanonical Wnt5a in hepatocellular carcinoma cells
Authors: Yuzugullu Haluk , Benhaj Khemais , Ozturk Nuri , Senturk Serif , Celik Emine , Toylu Asli , Tasdemir Nilgun , Yilmaz Mustafa , Erdal Esra , Akcali Kamil Can , Atabey Nese , Ozturk Mehmet
Published: October 2009

Background

β-catenin mutations that constitutively activate the canonical Wnt signaling have been observed in a subset of hepatocellular carcinomas (HCCs). These mutations are associated with chromosomal stability, low histological grade, low tumor invasion and better patient survival. We hypothesized that canonical Wnt signaling is selectively activated in well-differentiated, but repressed in poorly differentiated HCCs. To this aim, we characterized differentiation status of HCC cell lines and compared their expression status of Wnt pathway genes, and explored their activity of canonical Wnt signaling.

Results

We classified human HCC cell lines into "well-differentiated" and "poorly differentiated" subtypes, based on the expression of hepatocyte lineage, epithelial and mesenchymal markers. Poorly differentiated cell lines lost epithelial and hepatocyte lineage markers, and overexpressed mesenchymal markers. Also, they were highly motile and invasive. We compared the expression of 45 Wnt pathway genes between two subtypes. TCF1 and TCF4 factors, and LRP5 and LRP6 co-receptors were ubiquitously expressed. Likewise, six Frizzled receptors, and canonical Wnt3 ligand were expressed in both subtypes. In contrast, canonical ligand Wnt8b and noncanonical ligands Wnt4, Wnt5a, Wnt5b and Wnt7b were expressed selectively in well- and poorly differentiated cell lines, respectively. Canonical Wnt signaling activity, as tested by a TCF reporter assay was detected in 80% of well-differentiated, contrary to 14% of poorly differentiated cell lines. TCF activity generated by ectopic mutant β-catenin was weak in poorly differentiated SNU449 cell line, suggesting a repressive mechanism. We tested Wnt5a as a candidate antagonist. It strongly inhibited canonical Wnt signaling that is activated by mutant β-catenin in HCC cell lines.

Conclusion

Differential expression of Wnt ligands in HCC cells is associated with selective activation of canonical Wnt signaling in well-differentiated, and its repression in poorly differentiated cell lines. One potential mechanism of repression involved Wnt5a, acting as an antagonist of canonical Wnt signaling. Our observations support the hypothesis that Wnt pathway is selectively activated or repressed depending on differentiation status of HCC cells. We propose that canonical and noncanonical Wnt pathways have complementary roles in HCC, where the canonical signaling contributes to tumor initiation, and noncanonical signaling to tumor progression.
Pathophysiology of cell phone radiation: oxidative stress and carcinogenesis with focus on male reproductive system
Authors: Desai Nisarg R , Kesari Kavindra K , Agarwal Ashok
Published: October 2009

Hazardous health effects stemming from exposure to radiofrequency electromagnetic waves (RF-EMW) emitted from cell phones have been reported in the literature. However, the cellular target of RF-EMW is still controversial. This review identifies the plasma membrane as a target of RF-EMW. In addition, the effects of RF-EMW on plasma membrane structures (i.e. NADH oxidase, phosphatidylserine, ornithine decarboxylase) and voltage-gated calcium channels are discussed. We explore the disturbance in reactive oxygen species (ROS) metabolism caused by RF-EMW and delineate NADH oxidase mediated ROS formation as playing a central role in oxidative stress (OS) due to cell phone radiation (with a focus on the male reproductive system). This review also addresses: 1) the controversial effects of RF-EMW on mammalian cells and sperm DNA as well as its effect on apoptosis, 2) epidemiological, in vivo animal and in vitro studies on the effect of RF-EMW on male reproductive system, and 3) finally, exposure assessment and dosimetry by computational biomodeling.
Leptin interferes with 3',5'-Cyclic Adenosine Monophosphate (cAMP) signaling to inhibit steroidogenesis in human granulosa cells
Authors: Lin Qing , Poon Song Ling , Chen Junling , Cheng Linan , HoYuen Basil , Leung Peter CK
Published: October 2009

Background

Obesity has been linked to an increased risk of female infertility. Leptin, an adipocytokine which is elevated during obesity, may influence gonadal function through modulating steroidogenesis in granulosa cells.

Methods

The effect of leptin on progesterone production in simian virus 40 immortalized granulosa (SVOG) cells was examined by Enzyme linked immunosorbent assay (ELISA). The effect of leptin on the expression of the steroidogenic enzymes (StAR, P450scc, 3betaHSD) in SVOG cells was examined by real-time PCR and Western blotting. The mRNA expression of leptin receptor isoforms in SVOG cells were examined by using PCR. SVOG cells were co-treated with leptin and specific pharmacological inhibitors to identify the signaling pathways involved in leptin-reduced progesterone production. Silencing RNA against leptin receptor was used to determine that the inhibition of leptin on cAMP-induced steroidogenesis acts in a leptin receptor-dependent manner.

Results and Conclusion

In the present study, we investigated the cellular mechanisms underlying leptin-regulated steroidogenesis in human granulosa cells. We show that leptin inhibits 8-bromo cAMP-stimulated progesterone production in a concentration-dependent manner. Furthermore, we show that leptin inhibits expression of the cAMP-stimulated steroidogenic acute regulatory (StAR) protein, the rate limiting de novo protein in progesterone synthesis. Leptin induces the activation of ERK1/2, p38 and JNK but only the ERK1/2 (PD98059) and p38 (SB203580) inhibitors attenuate the leptin-induced inhibition of cAMP-stimulated StAR protein expression and progesterone production. These data suggest that the leptin-induced MAPK signal transduction pathway interferes with cAMP/PKA-stimulated steroidogenesis in human granulosa cells. Moreover, siRNA mediated knock-down of the endogenous leptin receptor attenuates the effect of leptin on cAMP-induced StAR protein expression and progesterone production, suggesting that the effect of leptin on steroidogenesis in granulosa cells is receptor dependent. In summary, leptin acts through the MAPK pathway to downregulate cAMP-induced StAR protein expression and progesterone production in immortalized human granulosa cells. These results suggest a possible mechanism by which gonadal steroidogenesis could be suppressed in obese women.
Human T cells express CD25 and Foxp3 upon activation and exhibit effector/memory phenotypes without any regulatory/suppressor function
Authors: Kmieciak Maciej , Gowda Madhu , Graham Laura , Godder Kamar , Bear Harry D , Marincola Francesco M , Manjili Masoud H
Published: October 2009

Background

Foxp3 has been suggested to be a standard marker for murine Tregs whereas its role as marker for human Tregs is controversial. While some reports have shown that human Foxp3+ T cells had no regulatory function others have shown their role in the inhibition of T cell proliferation.

Methods

T cell activation was performed by means of brayostatin-1/ionomycin (B/I), mixed lymphocyte reaction (MLR), and CD3/CD28 activation. T cell proliferation was performed using BrdU and CFSE staining. Flow cytometry was performed to determine Foxp3 expression, cell proliferation, viabilities and phenotype analyses of T cells.

Results

Both CD4+ and CD8+ T cells expressed Foxp3 upon activationin vitro. Expression of Foxp3 remained more stable in CD4+CD25+ T cells compared to that in CD8+CD25+ T cells. The CD4+CD25+Foxp3+ T cells expressed CD44 and CD62L, showing their effector and memory phenotypes. Both FoxP3- responder T cells and CD4+FoxP3+ T cells underwent proliferation upon CD3/CD28 activation.

Conclusion

Expression of Foxp3 does not necessarily convey regulatory function in human CD4+CD25+ T cells. Increased FoxP3 on CD44+ effector and CD44+CD62L+ memory T cells upon stimulation suggest the activation-induced regulation of FoxP3 expression.
Pollen allergens do not come alone: pollen associated lipid mediators (PALMS) shift the human immue systems towards a TH2-dominated response
Authors: Gilles Stefanie , Mariani Valentina , Bryce Martina , Mueller Martin J , Ring Johannes , Behrendt Heidrun , Jakob Thilo , Traidl-Hoffmann Claudia
Published: October 2009

Pollen allergy is characterized by a TH2-biased immune response to pollen-derived allergens. However, pollen-exposed epithelia do not encounter pure allergen but rather a plethora of protein and non-protein substances. We demonstrated that pollen liberate lipids with chemical and functional similarities to leukotriens and prostaglandins - the pollen associated lipid mediators (PALMs). To date, two main groups of PALMs have been characterized: The immunostimulatory PALMs activating innate immune cells such as neutrophils and eosinophils, and the immunomodulatory E1-phytoprostanes blocking IL-12 production of dendritic cells, resulting in the preferential induction of TH2 responses. This article reviews our work in the field of PALMs and their effects on cells of the innate and adoptive immune system. From recent results a general picture starts to emerge in which PALMs (and possibly other pollen-associated substances) may - independently from protein allergens - propagate an overall TH2 favoring micromilieu in pollen exposed tissue of predisposed individuals.
Ginseng leaf-stem: bioactive constituents and pharmacological functions
Authors: Wang Hongwei , Peng Dacheng , Xie Jingtian
Published: October 2009

Ginseng root is used more often than other parts such as leaf stem although extracts from ginseng leaf-stem also contain similar active ingredients with pharmacological functions. Ginseng's leaf-stems are more readily available at a lower cost than its root. This article reviews the pharmacological effects of ginseng leaf-stem on some diseases and adverse effects due to excessive consumption. Ginseng leaf-stem extract contains numerous active ingredients, such as ginsenosides, polysaccharides, triterpenoids, flavonoids, volatile oils, polyacetylenic alcohols, peptides, amino acids and fatty acids. The extract contains larger amounts of the same active ingredients than the root. These active ingredients produce multifaceted pharmacological effects on the central nervous system, as well as on the cardiovascular, reproductive and metabolic systems. Ginseng leaf-stem extract also has anti-fatigue, anti-hyperglycemic, anti-obesity, anti-cancer, anti-oxidant and anti-aging properties. In normal use, ginseng leaf-stem extract is quite safe; adverse effects occur only when it is over dosed or is of poor quality. Extracts from ginseng root and leaf-stem have similar multifaceted pharmacological activities (for example central nervous and cardiovascular systems). In terms of costs and source availability, however, ginseng leaf-stem has advantages over its root. Further research will facilitate a wider use of ginseng leaf-stem.
RETRACTED ARTICLE: Conservative management for an esophageal perforation in a patient presented with delayed diagnosis: a case report
Authors: Tsalis Konstantinos , Blouhos Konstantinos , Kapetanos Dimitrios , Kontakiotis Theodore , Lazaridis Charalampos
Published: October 2009

Background

Esophageal perforation is a serious condition with a high mortality rate. Successful therapy depends on the size of the rupture; the time elapsed between rupture and diagnosis, and the underlying health of the patient. Common causes of esophageal perforation include medical instrumentation, foreign-body ingestion, and trauma.

Case report

A case of esophageal perforation due to fish bone ingestion in a 67-year-old male is described here, with a review of the pertinent literature. The patient presented with chest pain, fever and right-sided pleural effusion. Initial evaluation was nondiagnostic. The water-soluble contrast swallow test showed no evidence of leakage. Computed tomography scan demonstrated a pneumomediastinum, and right-sided hydropneumothorax.

Conclusion

The patient was successfully treated using conservative measures.