bluuebunny/crossref_metadata_2025 huggingface dataset:
No News Is Good News
Authors: Abdiel Douglas
Published: January 2010

The Australian government and military have maintained humanitarian interventions for far longer than any comparable U.S. humanitarian intervention. This longevity confounds most traditional international relations theories. It seems that the key variable is public support for humanitarian interventions. The U.S. public quickly grew impatient with humanitarian operations, while the Australian public has not yet done so. Two reasons for the Australian public’s forbearance are explored. First, the idea that the Australian military and government are proficient at these operations and that the public supports these operations because it “loves a winner” is found wanting. Second, innate differences between the United States and Australia, particularly regarding news media, are explored; these differences seem to be highly correlated with the longevity of the operations. It seems likely that the Australian public does not hear enough about these operations to be concerned about them or question their utility, efficacy, or cost.
Is it the patient or the physician who cannot tolerate anemia? A prospective analysis in 1854 non-transfused coronary artery surgery patients
Authors: Senay Sahin , Toraman Fevzi , Karabulut Hasan , Alhan Cem
Published: January 2010

Background and objective: Low hematocrit level and transfusion may coexist during cardiopulmonary bypass and the actual impact of one on the outcome parameters may be counfounded or masked by the other. This study aims to determine the impact of the lowest hematocrit level during cardiopulmonary bypass on outcome parameters in non-transfused patients. Methods: Two thousand six hundred and thirty-two consecutive patients who underwent isolated coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass were evaluated prospectively:1854 (70.4%) patients who did not receive any red blood cells during hospital stay were included in the study. Perioperative data and outcome parameters were recorded. Outcomes were evaluated in 2 groups according to the lowest level of hematocrit (>21%: high hematocrit group, n= 1680, (91.6%) and ≤21%: low hematocrit group, n=174, (9.4%)) during cardiopulmonary bypass. Results: Overall mean lowest hematocrit level of patients was 27.7±4.4% (19.7±1.9% in the low hematocrit group, 28.5±4.1% in the high hematocrit group). The comparison of outcome parameters regarding the time on ventilator, duration of intensive care unit stay, intensive care unit re-admission, hospital re-admission, reoperation for bleeding or tamponade, low cardiac output, postoperative atrial fibrillation, stroke, creatinine level at hospital discharge, new onset renal failure, mediastinitis, pulmonary complication and mortality rates were similar in both groups. Conclusions: Our findings suggest that a lowest hematocrit level of ≤21% during cardiopulmonary bypass has no adverse impact on outcome after isolated coronary surgery in non-transfused patients.
A clinical comparison of bubble elimination in Quadrox and Polystan oxygenators
Authors: Jirschik Mario , Keyl Cornelius , Beyersdorf Friedhelm
Published: January 2010

Background: Microbubbles generated during heart surgery on extracorporeal circulation have been implicated as a possible cause of postoperative neurocognitive dysfunction and negative outcome. The main sources of microbubbles in the extracorporeal circuit are air leaking from the venous cannulation site, air delivered by drug and volume administration, during the taking of blood samples, during hemofiltration, and by using vacuum-assisted venous drainage (VAVD). Membrane oxygenators, although not designed for the elimination of gaseous microbubbles, can eliminate much of this air. Aim of the study / hypothesis: The aim of this study was to test the hypothesis that the amount of microbubbles passing through the oxygenator varies depending on the oxygenator design. Methods: one hundred patients undergoing aortic valve replacement with cardiopulmonary bypass (CPB) were included in a retrospective clinical trial assessing the bubble elimination of the two oxygenators routinely used in our clinic. The oxygenators (Quadrox-i Adult / Polystan Safe Maxi) are manufactured with the same hollow-fiber material, but display different designs. Bubbles were detected by a two-channel ultrasound bubble counter. The probes were placed directly at the inlet and the outlet of the oxygenators. The filtration index was calculated by the bubble counter as a measure of the percentage reduction of bubble volume and number. Results: The Quadrox has a significantly higher filtration index (92.3% [89.7; 95.1], median [25th,75th percentile]) than the Polystan (74.9% [64.2;80.9], p<0.001), indicating the superior ability of the Quadrox to eliminate microbubbles. Conclusion: Our study demonstrates major differences in the capacity of bubble elimination of the oxygenators being investigated, possibly depending on oxygenator design.
Microemboli are not associated with delirium after coronary artery bypass graft surgery
Authors: Rudolph James L. , Babikian Viken L. , Treanor Patrick , Pochay Val E. , Wigginton Jeremy B. , Crittenden Michael D. , Marcantonio Edward R.
Published: January 2010

Delirium is an acute change in cognition which occurs frequently after coronary artery bypass graft (CABG) surgery. Cerebral microemboli, from plaque, air, or thrombus, have been hypothesized to contribute to delirium and cognitive decline after CABG. The purpose of this study was to determine if there was an association between cerebral microemboli and delirium after cardiac surgery. Non-delirious patients (n=68) were prospectively enrolled and underwent intraoperative monitoring of the middle cerebral arteries with transcranial Doppler (TCD). TCD signals were saved and analyzed postoperatively for microemboli manually, according to established criteria. Postoperatively, patients were assessed for delirium with a standardized battery. Thirty-three patients (48.5%) developed delirium after surgery. Microemboli counts (mean ± SD) were not significantly different in those with and without delirium (303 ± 449 vs. 299 ± 350; p=0.97). While intraoperative microemboli were not associated with delirium after CABG, further investigation into the source and composition of microemboli can further elucidate the long-term clinical impact of microemboli.
Effect of intra-aortic balloon pump support on microcirculation during high-risk percutaneous intervention
Authors: Jung Christian , Lauten Alexander , Rödiger Christoph , Krizanic Florian , Figulla Hans R , Ferrari Markus
Published: January 2010

Background: Intra-aortic balloon counter-pulsation (IABP) is recommended for hemodynamic support in cardiogenic shock. In addition, it can be applied during high-risk percutaneous interventions (PCI). While IABP support improves microflow in cardiogenic shock, its effect in hemodynamically stable patients is still unclear. We, therefore, sought to evaluate the effect of IABP treatment on microflow in hemodynamically stable patients undergoing elective high-risk PCI. Methods: In six patients with >" xbd="892" xhg="869" ybd="1310" yhg="1284"/>50% left main stenosis, microflow was evaluated according to current guidelines, using side-stream dark-field microscopy, visualizing microcirculatory vessels without using fluorescent dyes. Microflow was analyzed separately for each vessel category (diameter: 10-25µm and 26-50µm), using a semiquantitative system (0= no flow; 1= intermittent flow; 2= sluggish flow; 3= continuous flow) by a trained investigator. Steady state recordings and additional recordings twenty seconds after discontinuation of the electively implanted IABP were acquired. Results: Microflow in vessel categories 10-25µm and 26-50µm increased in this group of hemodynamically stable patients on use of IABP. Microflow decreased from 2.73±0.39 (p=0.052; 26-50µm: 2.88±0.20, p=0.008) to 2.22±0.23 (2.18±0.45) after stopping the IABP and increased to 2.90±0.14 (p=0.009; 2.85±0.28, p=0.009) after restart of the IABP. Conclusions: Circulatory support with IABP increases microcirculatory flow in the smallest vessels of the sublingual mucosa. Our data support the hypothesis that intra-aortic balloon counter-pulsation increases coronary and microvascular perfusion, thus, improving microcirculation even in hemodynamically stable patients. The use of IABP may increase safety of complex PCI and decrease the risk of deleterious complications.
Long-term assessment of NFκB expression in the brain and neurologic outcome following deep hypothermic circulatory arrest in rats
Authors: Kellermann Kristine , Gordan M. Lucia , Nollert Georg , Blobner Manfred , Kochs Eberhard F. , Jungwirth Bettina
Published: January 2010

Objectives: Inflammatory response is discussed as a contributor to neurologic deficits following cardiac surgery using deep hypothermic circulatory arrest (DHCA). Nuclear Factor Kappa B (NFκB) presents a central transcription factor whose expression pattern and subsequent role very much depend on the type and manner of cerebral injury. This study was designed to assess the time course of cerebral NFκB expression in relation to neurologic performance over 28 days following 45min of DHCA in rats. Methods: With Institutional Review Board approval, 30 rats were subjected to cardiopulmonary bypass (CPB) with 45min of DHCA (rectal temperature 15-18°C) and randomly assigned to 1, 3, 7, 14 and 28 days of postoperative survival. Untreated animals served as control (n=6). Cerebral NFκB expression was analyzed immunohistochemically, cyclooxygenase-2 (COX-2) and inhibitor of kappa B-alpha (IκBα) using Western Blot and the number of eosinophilic neurons with hematoxylin and eosin (HE) staining. Neurologic outcome was assessed pre- and postoperatively. Results: Neuronal expression of NFκB in the hippocampus peaked at day one, remaining elevated in the motor cortex until day 28. Rats showed neurologic deficits on postoperative day one. Cerebral COX-2 was increased during the first postoperative week and IκBα peaked on day 14. Histologic damage in the motor cortex and hippocampus persisted until day 28. No systemic inflammation was detectable postoperatively. Conclusions: Postoperative day one presents with the highest NFκB-expression in the ischemia-sensitive hippocampus, accompanied by neurologic dysfunction and histologic damage following 45min of DHCA in rats.
No clear clinical benefit of using mini-invasive extracorporeal circulation in coronary artery bypass grafting in low-risk patients
Authors: Svitek Vladimir , Lonsky Vladimir , Mandak Jiri , Krejsek Jan , Kolackova Martina , Brzek Vladimir , Kubicek Jaroslav , Volt Martin , Bartos Michael , Harrer Jan
Published: January 2010

Background: Current research is engaged in innovative technologies of extracorporeal circulation (ECC) systems in an effort to eliminate negative effetcs. Some studies have shown that, due to the complexity of technical settings of mini-ECC, they invoke a weaker immune response compared to classic ECC. The clinical benefits of using these systems have not been clearly proven yet. Methods: A group of 54 patients who were indicated for elective coronary surgery were randomised into two groups — Group A (patients operated on using classic ECC - open modification) and Group B (patients operated on using mini-ECC). The concentrations of IL-6, PMN elastase and MCP-1 in both groups were monitored per- and postoperatively, along with the postoperative clinical course. Results: The groups did not differ in the basic pre- and peroperative characteristics. We recorded a lower priming for mini-ECC (p < 0.001) and significantly reduced hemodilution during ECC. There were no differences in the clinical outcome in either group. Serum concentrations of monitored markers of immune reaction towards ECC showed higher activity during standard ECC. Conclusion: New technologies used in mini-systems have proven to lower activation of the immune system, which can be monitored using kinetics of proinflammatory mediators. In spite of these comparable laboratory results, we did not find differences in short-term clinical results when comparing both these groups of low-risk patients.
Cardiac Tamponade in a Patient With Dengue Fever and Lupus Nephritis: A Case Report
Authors: Kumar Sunil , Iuga Alina , Jean Raymonde
Published: January 2010

Cases of small pericardial effusion have been reported in association with dengue fever (DF), largely with dengue hemorrhagic fever during epidemic outbreaks. However, cardiac tamponade developed by a patient with DF has not yet been reported in the English literature. We report a case of cardiac tamponade in a patient with DF and lupus nephritis. We describe the characteristic features to differentiate pericardial effusion of lupus origin from that of viral etiology. A 59-year-old Hispanic woman presented to the emergency department with complaints of 5 to 6 days of fever, myalgia, headache, and retro-orbital pain. Her symptoms started 3 days after returning from the Dominican Republic, where a dengue outbreak was reported. Her past medical history was significant for hypertension and lupus nephritis diagnosed 3 months earlier. On day 2, patient developed a large pericardial effusion that progressed to tamponade over the next 2 days, requiring surgical drainage. Subsequently, the patient improved; however, serological analysis did not suggest any lupus flare-up. Pericardial fluid analysis showed hypocellularity without lupus erythematosus cell and biopsy revealed only reactive mesothelial cells suggestive of viral etiology. Dengue serology was reported as markedly elevated, supporting a diagnosis of classic DF (both immunoglobulin M [IgM] titer 2.93 and IgG titer 12.13 by enzyme-linked immunosorbent assay [ELISA]; reference range: <0.90 for both). Absence of rise in serum antinuclear antibody (ANA) titer correlated with lack of inflammatory changes on the pericardium favored viral etiology over lupus origin. This differentiation is pertinent from a management perspective.
Differentiation of Bone Marrow Stromal Cells into Osteoblasts in a Self-assembling Peptide Hydrogel: In Vitro and In Vivo Studies
Authors: Ozeki Maho , Kuroda Shinji , Kon Kazuhiro , Kasugai Shohei
Published: January 2010

A prerequisite of tissue engineering approaches with regard to autograft is a suitable scaffold that can harbor cells and signals. Conventionally, such scaffolds have been prepared as 3D scaffolds prefabricated from synthetic or natural biomaterials. RAD16 has been introduced as a new biomaterial, where synthetic peptides self-assemble to form a hydrogel. In this study, RAD16 was examined in terms of osteogenic efficacy and feasibility of ectopic mineralization.

Two hundred and seventy-one RAD16 was cocultured with 1 × 106 bone marrow cells from the femurs of 6-week-old Wistar male rats in alpha minimum essential medium supplemented with or without dexamethasone. Second, the same volume of the RAD16 construct hosting the cells with or without hydroxyapatite (HA) particles was treated in the dexamethasone medium as well, prepared in a Teflon tube, and implanted subcutaneously. Cell proliferation was prominent in the RAD16 coculture with dexamethasone at 1 week and significantly decreased by 2 weeks, whereas the other combinations remained or inclined, and their osteogenic differentiation was accelerated up to 2 weeks, as seen in increasing alkaline phosphatase (ALP) activity and mRNAs of ALP, OPN, and OCN. The RAD16 implant prepared with HA particles allowed more osteoblast-like cells and blood cells to grow inside, which was accompanied by elevating OPN gene expression and the stronger peak of VEGF gene expression at 2 weeks. Furthermore, more OPN mRNA signal was detected around the RAD16 containing HA particles by 4 weeks. On the other hand, the RAD16 alone represented lower expression of OPN gene. During the experiment, however, no ectopic mineralization was observed in both groups. Conclusively, it was suggested that the RAD16 showed feasibility of serving as a matrix for osteogenic differentiation of cocultured bone marrow cells in vitro and in vivo. Proceeding of exploration and modification of RAD16 are continuously required for cell-based tissue engineering.
Fossils as Candidate Material for Orthopedic Applications
Authors: Pesenti Hector , Leoni Matteo , Motta Antonella , Scardi Paolo
Published: January 2010

Ceramic powders from fossil deposits were thoroughly characterized from the material point of view and sintered to produce massive components. The raw material, a mixture of apatite minerals, feldspars, and quartz, seems ideally suitable to obtain a biologically compatible glass ceramic. Preliminary in vitro tests of proliferation and adhesion of MG63 human osteoblast-like cell line on a selected sample are encouraging. Results are correlated with sintering conditions and phase composition: the fossil can be sintered to almost full density at temperatures as low as 900°C and seems to quickly promote cell activation with respect to hydroxylapatite.
IT Use and Declining Social Capital?
Authors: Robinson John P. , Martin Steven
Published: January 2010

Early studies of the impact of information technology (IT) on society suggested that it had a negative impact on social life as well as on mass media use. This article reviews the results from several subsequent studies both in the United States and other countries that show little such societal change in terms of users’ daily behavior. It then proceeds to document further negative evidence from two more recent large national surveys with high response rates: the 2006 General Social Survey (GSS), with more than 2,500 respondents, and the 2003—2005 American Time-Use Survey (ATUS), with more than 40,000 respondents, aged 18 and older. The GSS survey collected time-estimate data on particular social and media (mainly free-time) activities, while the ATUS study collected diary data on all daily activities across a single day. In general, Internet use was not consistently correlated with significantly lower levels of socializing or other social activities (such as church attendance) nor with lower time with mass communications media in the GSS. For reading and some other behaviors, the Internet was associated with increased media use. Respondents who reported more time on the Internet did report fewer social visits with relatives, but more visits with friends, compared to those who spent no time on the Internet. The main difference between users and nonusers in the ATUS was with time at paid work, which was only partially explained by higher Internet use by teens and on days off from work. For reading and some other behaviors, the Internet was associated with increased use.
Stability of Career Aspirations: A Longitudinal Test of Gottfredson’s Theory
Authors: Junk Kate E. , Armstrong Patrick Ian
Published: January 2010

Gottfredson’s theory of the career compromise process was evaluated using a longitudinal data set of 2,353 female and 321 male students recruited for Zuckerman’s Seven College Study, who reported their career aspirations twice over a 1-year period. Expressed career aspirations were coded on the dimensions of sex type, prestige, and the interest-based Things/People and Data/Ideas dimensions. Stability of aspirations over an 1-year period were analyzed using partial correlation analyses to control for the nonindependence of measures. Discrepancies between current and idealized career aspirations were also examined using the same methods. Contrary to predictions based on Gottfredson’s theory, student career aspirations were more stable along the prestige and Things/People dimensions than on the sex type dimension. Implications for theory, research, and career counseling practice are discussed.
Sweet Future
Authors: Wang X.T. , Dvorak Robert D.
Published: January 2010

This study explored metabolic mechanisms of future (delay) discounting, a choice phenomenon where people value present goods over future goods. Using fluctuating blood glucose as an index of body-energy budget, optimal discounting should regulate choice among rewards as a function of temporal caloric requirement. We identified this novel link between blood glucose levels measured in the lab and future-discounting rates of participants, who made choices between a “smaller and sooner” reward and a “larger but later” option, with possible actual monetary rewards. A group of participants who drank a soft drink that contained sugar showed a reduced rate of future discounting afterward, when we controlled for sex, age, body mass index, and the taste of the drink. In contrast, a group of participants who drank a soft drink that contained artificial sweetener showed an increased rate of future discounting. Blood glucose levels not only varied as a result of caloric intake but also regulated the rate of future discounting, according to participants’ dynamic body-energy budget.
Review: Lupus nephritis: pathologic features, epidemiology and a guide to therapeutic decisions
Authors: Ortega LM , Schultz DR , Lenz O. , Pardo V. , Contreras GN
Published: January 2010

Systemic lupus erythematosus may present with renal manifestations that frequently are difficult to categorize and lupus nephritis is an important predictor of poor outcome. The type and spectrum of renal injury may remain undiagnosed until full-blown nephritic and/or nephrotic syndrome appear with increased risk of end-stage renal disease. These abnormalities occur within the first few years after the diagnosis of lupus is made on clinical grounds and with the support of laboratory tests in high risk patients. An early renal biopsy is helpful in patients with an abnormal urinalysis and/or reduced glomerular filtration rate and the results form the basis for therapeutic decisions. The biopsy also provides vital prognostic information based on histological categorization of different types of lupus nephritis, the degree of activity, chronicity and the immunopathogenesis. In the current armamentarium, the use of cyclophosphamide and azathioprine and recently mycophenolate mofetil, reduce morbidity and maintenance therapies reduce the risk of end-stage renal disease. Clinical trials underway promise new, effective and safe immunosuppressive regimens for the treatment of proliferative lupus nephritis.
Work-Family Balance as a Potential Strategic Advantage: a Hotel General Manager Perspective
Authors: Qu Xiao  , O'Neill John W.
Published: January 2010

This qualitative study is an exploratory attempt to investigate hotel general managers’ (GMs) perceived work—family balance/interface issues from a strategic perspective. Based on 49 in-person, in-depth, in-office, interviews with full-service hotel GMs, the authors identify current strategic issue perceptions (SIPs) of hotel GMs and explore potential relationships between these SIPs and work—family issues in the hotel industry. Findings suggest that work—family issues, including workplace flexibility, turnover, knowledge management, and career advancement are influenced by hotel culture and the GM’s management style; and when human resources are perceived as a competitive advantage by the hotel GMs, the work—family issues are indeed related to the hotel GM’s perceived strategic issues.
Homicide Among Pregnant and Postpartum Women in the United States: A Review of the Literature
Authors: Samandari Ghazaleh , Martin Sandra L. , Schiro Sharon
Published: January 2010

Eighteen articles that examined the extent of homicide among pregnant and/or postpartum women in the United States are reviewed, documenting the studies’ methods and findings. Results from proportional mortality analyses (studies that examined only deaths, rather than deaths within a larger population of living individuals) showed a modicum of support for the contention that homicide may account for a greater proportion of the deaths among pregnant/postpartum women than among other women of reproductive age. However, results from more comprehensive analyses that estimated homicide risks/rates (studies that examined deaths within the context of living populations) did not find any evidence to suggest that pregnant/postpartum women experience a greater risk/rate of homicide compared to other women of reproductive age. This difference in findings is discussed in light of the different methodological approaches.
How Are We Measuring Resilience Following Childhood Maltreatment? Is the Research Adequate and Consistent? What is the Impact on Research, Practice, and Policy?
Authors: Walsh Wendy A. , Dawson Jean , Mattingly Marybeth J.
Published: January 2010

The authors review the literature on resilience following childhood maltreatment and describe how variation in the measurement of outcomes at various developmental stages affects research findings, practice implications, and policy recommendations. Although the 21 studies reviewed considered competent functioning in similar domains as evidence of resilience following maltreatment, few provided prevalence estimates for specific indicators or across domains of functioning. Using the National Survey of Child and Adolescent Well-Being (NSCAW), the authors explored different ways of operationalizing resilience. The number of children demonstrating competence following maltreatment varied greatly by the indicators used; furthermore, competence in one domain (behavioral, emotional, or educational) did not guarantee competence in another. About one in five children were functioning poorly in all three domains. Because findings vary according to the operational definition of resilience, researchers must use caution in conceptualizing their analytic variables and interpreting findings. Furthermore, given the lack of cross-domain competence, services to maltreated children and their families should be comprehensive.
A randomised controlled trial of clinical supervision: selected findings from a novel Australian attempt to establish the evidence base for causal relationships with quality of care and patient outcomes, as an informed contribution to mental health nursing practice development
Authors: White Edward , Winstanley Julie
Published: January 2010

This paper reports on selected findings from a novel randomised controlled trial (RCT) conducted in mental health settings in Queensland, Australia. Several national and state reports recently revealed the sub-optimal state of Australian mental health service provision which have direct implications for mental health nursing, including the privately experienced cost of working and coping in these settings. Clinical supervision (CS), a structured staff support arrangement, has shown promise as a positive contribution to the clinical practice development agenda and is now found reflected in health policy themes elsewhere in the world. However, CS is underdeveloped in Australia and the empirical evidence base for the informed implementation of CS, per se, has remained elusive. Within the overall context of a RCT design, therefore, and supplemented by other data collection methods, this large and generously funded study attempted to make an incremental contribution to better understanding this demanding substantive domain. Whilst the substantive insights and theoretical propositions reported here were derived from, and may be limited by, a sub-specialty of nursing and a single geographic location, they were earthed in the personal self-reported experience of those directly involved with a clinical practice innovation. They may resonate with counterparts beyond mental health nursing and Queensland, Australia, respectively, therefore, and may assist in both conceptualising and operationalising CS research, education, management, policy and clinical practice development decision making in the future.
Care and compromise: developing a conceptual framework for work-related stress
Authors: Freshwater Dawn , Cahill Jane
Published: January 2010

In this paper we argue that in the current global healthcare climate, practitioners’ ability to provide compassionate and high quality care is undermined on a daily basis, not least by the organisational priorities of cost containment, of science and technology and, paradoxically, innovations experienced as demands such as specialisation. It is not surprising that the financial and workforce constraints of the global healthcare system, now more than ever, affect the practitioners’ capacity to deliver the optimum level of care, care that is positively influenced by patient satisfaction, a current indicator of quality. Whilst the notions of quality and standards have increasingly become the concern of healthcare organizations, quality cannot be considered in isolation from the healthcare management and occupational health of the workforce. In this paper we argue that healthcare practitioners are especially vulnerable to stress because the very nature of caring as a profession demands high levels of emotional engagement and compromise. It is clear that at a time when healthcare systems are under-resourced and over-stretched, practitioners may experience additional stress, ironically at a time when services need to increase retention, recruitment and job satisfaction. We propose a conceptual framework of stress and compromise in relation to caring and a methodology for developing an intervention that would consider how compromise itself may be utilised and adapted to both alleviate stress and inform individual and professional development.
Identification of an alternative CD20 transcript variant in B-cell malignancies coding for a novel protein associated to rituximab resistance
Authors: Henry Carole , Deschamps Marina , Rohrlich Pierre-Simon , Pallandre Jean-René , Rémy-Martin Jean-Paul , Callanan Mary , Traverse-Glehen Alexandra , GrandClément Camille , Garnache-Ottou Francine , Gressin Remy , Deconinck Eric , Salles Gilles , Robinet Eric , Tiberghien Pierre , Borg Christophe , Ferrand Christophe
Published: January 2010

Human CD20 is a B-cell lineage–specific marker expressed by normal and leukemic B cells from the pre-B to the plasma-cell stages and is a target for rituximab (RTX) immunotherapy. A CD20 reverse transcriptase–polymerase chain reaction (PCR) on B-cell lines cDNA yielded a short PCR product (ΔCD20) corresponding to a spliced mRNA transcript linking the exon 3 and exon 7 ends. We established here that this novel, alternatively spliced CD20 transcript is expressed and detectable at various levels in leukemic B cells, lymphoma B cells, in vivo tonsil- or in vitro CD40L-activated B cells, and Epstein-Barr virus (EBV)–transformed B cells, but not in resting CD19+- or CD20+-sorted B cells from peripheral blood or bone marrow of healthy donors. The truncated CD20 sequence is within the reading frame, codes a protein of 130 amino acids (∼ 15-17 kDa) lacking large parts of the 4 transmembrane segments, suggesting that ΔCD20 is a nonanchored membrane protein. We demonstrated the translation into a ΔCD20 protein which is associated with the membrane CD20 protein and showed its involvement in RTX resistance. Study of patient samples before and after RTX resistance or escape confirms our in vitro findings.
CD44 activation in mature B-cell malignancies by a novel recurrent IGH translocation
Authors: Hu Xiao-Tong , Chen Yun-Wen , Liang Anthony C. T. , Au Wing-Yan , Wong Kai-Yau , Wan Thomas S. K. , Wong Michelle L. Y. , Shen Lijun , Chan Ka-Kui , Guo Tianhuan , Chu Kent-Man , Tao Qian , Chim Chor-Sang , Loong Florence , Choi William W. L. , Lu Liwei , So Chi-Chiu , Chan Li Chong , Kwong Yok-Lam , Liang Raymond H. S. , Srivastava Gopesh
Published: January 2010

Using inverse polymerase chain reaction, we identified CD44, located on chromosome 11p13, as a novel translocation partner of IGH in 9 of 114 cases of gastric, nongastric extranodal, follicular, and nodal diffuse large B-cell lymphoma (DLBCL). Notably, these translocations involving IGHSμ were detected in follicular lymphomas and exclusively in germinal center B cell-ike (GCB)–DLBCLs. CD44 is not expressed in reactive GC B cells. The IGHSμ/CD44 translocations substitute Sμ for the CD44 promoter and remove exon 1 of CD44, resulting in the overexpression of Iμ-CD44 hybrid mRNA transcripts activated from derivative 11 that encode a new CD44 variant lacking the leader peptide and with a unique C-terminus (CD44ΔEx1). When overexpressed in vitro in the CD44− GCB-DLBCL cell line BJAB, CD44ΔEx1–green fluorescent protein localized to the cytoplasm and nucleus, whereas CD44s–green fluorescent protein (standard form) localized to the plasma membrane. The ectopic expression of CD44ΔEx1 in BJAB cells enhanced their proliferation rate and clonogenic ability, indicating a possible pathogenic role of the translocation.
Nutritional control of gene expression in Drosophila larvae via TOR, Myc and a novel cis-regulatory element
Authors: Li Ling , Edgar Bruce A , Grewal Savraj S
Published: January 2010

Background

Nutrient availability is a key determinant of eukaryotic cell growth. In unicellular organisms many signaling and transcriptional networks link nutrient availability to the expression of metabolic genes required for growth. However, less is known about the corresponding mechanisms that operate in metazoans. We used gene expression profiling to explore this issue in developing Drosophila larvae.

Results

We found that starvation for dietary amino acids (AA's) leads to dynamic changes in transcript levels of many metabolic genes. The conserved insulin/PI3K and TOR signaling pathways mediate nutrition-dependent growth in Drosophila and other animals. We found that many AA starvation-responsive transcripts were also altered in TOR mutants. In contrast, although PI3K overexpression induced robust changes in the expression of many metabolic genes, these changes showed limited overlap with the AA starvation expression profile. We did however identify a strong overlap between genes regulated by the transcription factor, Myc, and AA starvation-responsive genes, particularly those involved in ribosome biogenesis, protein synthesis and mitochondrial function. The consensus Myc DNA binding site is enriched in promoters of these AA starvation genes, and we found that Myc overexpression could bypass dietary AA to induce expression of these genes. We also identified another sequence motif (Motif 1) enriched in the promoters of AA starvation-responsive genes. We showed that Motif 1 was both necessary and sufficient to mediate transcriptional responses to dietary AA in larvae.

Conclusions

Our data suggest that many of the transcriptional effects of amino acids are mediated via signaling through the TOR pathway in Drosophila larvae. We also find that these transcriptional effects are mediated through at least two mechanisms: via the transcription factor Myc, and via the Motif 1 cis-regulatory element. These studies begin to elucidate a nutrient-responsive signaling network that controls metabolic gene transcription in Drosophila.
F-Prostaglandin receptor regulates endothelial cell function via fibroblast growth factor-2
Authors: Keightley Margaret C , Brown Pamela , Jabbour Henry N , Sales Kurt J
Published: January 2010

Background

Prostaglandin (PG) F2α is a key regulator of endometrial function and exerts its biological action after coupling with its heptahelical G protein-coupled receptor (FP receptor). In endometrial adenocarcinoma the FP receptor expression is elevated. We have shown previously that PGF2α-FP receptor signalling in endometrial adenocarcinoma cells can upregulate several angiogenic factors including fibroblast growth factor-2 (FGF2). In the present study, we investigated the paracrine effect of conditioned medium produced via PGF2α-FP receptor signalling in endometrial adenocarcinoma cells stably expressing the FP receptor (Ishikawa FPS cells), on endothelial cell function.

Results

Conditioned medium (CM) was collected from FPS cells after 24 hrs treatment with either vehicle (V CM) or 100 nM PGF2α (P CM). Treatment of human umbilical vein endothelial cells (HUVECs) with P CM significantly enhanced endothelial cell differentiation (network formation) and proliferation. Using chemical inhibitors of intracellular signalling, we found that P CM-stimulated endothelial cell network formation was mediated by secretion of endothelial PGF2α and activation of endothelial FP receptors, following FGF2-FGFR1 signalling, phosphorylation of ERK1/2 and induction of COX-2. Whereas, P CM stimulation of endothelial cell proliferation occurred independently of PGF2α secretion via an FGF2-FGFR1-ERK1/2 dependent mechanism involving activation of the mTOR pathway.

Conclusions

Taken together, we have shown a novel mechanism whereby epithelial prostaglandin F2α-FP signalling regulates endothelial cell network formation and proliferation. In addition we provide novel in vitro evidence to suggest that prostaglandin F2α can directly regulate endothelial cell network formation but not endothelial cell proliferation. These findings have relevance for pathologies where the FP receptor is aberrantly expressed, such as endometrial adenocarcinoma, and provide in vitro evidence to suggest that targeting the FP receptor could provide an anti-angiogenic approach to reducing tumour vasculature and growth.
Cloning and expression of SOLD1 in ovine and caprine placenta, and their expected roles during the development of placentomes
Authors: Ushizawa Koichi , Takahashi Toru , Hosoe Misa , Kizaki Keiichiro , Hashizume Kazuyoshi
Published: January 2010

Background

The Ly-6 (Ly-6/uPAR) superfamily members share the Ly-6 domain defined by distinct disulfide bonding patterns between 8 or 10 cysteine residues. They comprise membrane- and secretory-type proteins. We recently reported the gene and protein characterization of the bovine secreted protein of Ly-6 domain 1 (SOLD1). Bovine SOLD1 is expressed in trophoblast mononucleate cells (TMCs) and is localized in the cotyledonary mesenchyme. Here, we compared the expression and functionality of SOLD1 among the ruminants. We examined mRNA expression by chorionic fibroblasts as a measure of one of the SOLD1 functions.

Results

Ovine and caprine SOLD1 mRNAs have 303 bp open reading frames and encode for deduced SOLD1 proteins with 100 amino acids, including a 22-aa-long signal peptide at the N-terminal. Both of the SOLD1 amino acid sequences have high similarities with the bovine sequence. Both SOLD1 mRNAs were also expressed in TMCs of cotyledons and intercotyledonary membranes. The mature SOLD1 proteins were localized in the mesenchymal villi of cotyledons after secretion. Bovine, ovine and caprine SOLD1 affected gene expression in mesenchymal fibroblasts in vitro; nucleoredoxin expression was upregulated and BCL2-like 13 was downregulated. Thus, we suggest that SOLD1 acts as a modulator of cell proliferation and apoptosis.

Conclusion

Expressing cells and protein localization of SOLD1 coincided among the three ruminants. SOLD1 participated in regulating nucleoredoxin and BCL2-like 13 expression in chorionic fibroblasts. SOLD1 is produced specifically in the cotyledons and intercotyledonary membranes in ruminants and appears to be involved in the construction of the ruminant placenta.
Identification and characterization of microRNAs and endogenous siRNAs in Schistosoma japonicum
Authors: Hao Lili , Cai Pengfei , Jiang Ning , Wang Heng , Chen Qijun
Published: January 2010

Background

Small endogenous non-coding RNAs (sncRNAs) such as small interfering RNA (siRNA), microRNA and other small RNA transcripts are derived from distinct loci in the genome and play critical roles in RNA-mediated gene silencing mechanisms in plants and metazoa. They are approximately 22 nucleotides long; regulate mRNA stability through perfect or imperfect match to the targets. The biological activities of sncRNAs have been related to many biological events, from resistance to microbe infections to cellular differentiation. The development of the zoonotic parasite Schistosoma japonicum parasite includes multiple steps of morphological alterations and biological differentiations, which provide a unique model for studies on the functions of small RNAs. Characterization of the genome-wide transcription of the sncRNAs will be a major step in understanding of the parasite biology. The objective of this study is to investigate the transcriptional profile and potential function of the small non-coding RNAs in the development of S. japanicum.

Results

The endogenous siRNAs were found mainly derived from transposable elements (TE) or transposons and the natural antisense transcripts (NAT). In contrast to other organisms, the TE-derived siRNAs in S. japonicum were more predominant than other sncRNAs including microRNAs (miRNAs). Further, there were distinct length and 3'end variations in the sncRNAs, which were associated with the developmental differentiation of the parasite. Among the identified miRNA transcripts, there were 38 unique to S. japonicum and 16 that belonged to 13 miRNA families are common to other metazoan lineages. These miRNAs were either ubiquitously expressed, or they exhibited specific expression patterns related to the developmental stages or sex. Genes that encoded miRNAs are mainly located in clusters within the genome of S. japonicum. However, genes within one cluster could be differentially transcribed, which suggested that individual genes might be regulated by distinct mechanisms during parasite development.

Conclusions

Many miRNA and endogenous siRNA transcripts were identified in S. japonicum and the amount of siRNA was at least 4.4 and 1.6 times more than that of miRNA in both schistosomulum and adult worm stages respectively. SiRNAs are mainly derived from transposable elements (or transposons); while natural antisense transcripts (NAT)-derived siRNAs were much less. A majority of miRNA transcripts identified in the parasite were species-specific and the expression of certain miRNAs was found developmentally regulated. Both miRNA and siRNAs are potentially important regulators in the development of schistosomal parasites.
Large effects on body mass index and insulin resistance of fat mass and obesity associated gene (FTO) variants in patients with polycystic ovary syndrome (PCOS)
Authors: Tan Susanne , Scherag André , Janssen Onno Eilard , Hahn Susanne , Lahner Harald , Dietz Tiina , Scherag Susann , Grallert Harald , Vogel Carla Ivane Ganz , Kimmig Rainer , Illig Thomas , Mann Klaus , Hebebrand Johannes , Hinney Anke
Published: January 2010

Background

The polycystic ovary syndrome (PCOS), a common endocrine disorder in women of child-bearing age, mainly characterised by chronic anovulation and hyperandrogenism, is often associated with insulin resistance (IR) and obesity. Its etiology and the role of IR and obesity in PCOS are not fully understood. We examined the influence of validated genetic variants conferring susceptibility to obesity and/or type 2 diabetes mellitus (T2DM) on metabolic and PCOS-specific traits in patients with PCOS.

Methods

We conducted an association study in 386 patients with PCOS (defined by the Rotterdam-criteria) using single nucleotide polymorphisms (SNPs) in or in proximity to the fat mass and obesity associated gene(FTO), insulin-induced gene-2 (INSIG2), transcription factor 7-like 2 gene (TCF7L2) and melanocortin 4 receptor gene (MC4R). To compare the effect ofFTOobesity risk alleles on BMI in patients with PCOS to unselected females of the same age range we genotyped 1,971 females from the population-based KORA-S4 study (Kooperative Gesundheitsforschung im Raum Augsburg, Survey 4).

Results

TheFTOrisk allele was associated with IR traits and measures of increased body weight. In addition, theTCF7L2SNP was associated with body weight traits. For the SNPs in the vicinity ofINSIG2andMC4Rand for the other examined phenotypes there was no evidence for an association. In PCOS the observed per risk allele effect ofFTOintron 1 SNP rs9939609 on BMI was +1.56 kg/m2, whereas it was +0.46 kg/m2in females of the same age range from the general population as shown previously.

Conclusion

The stronger effect on body weight of theFTOSNP in PCOS might well have implications for the etiology of the disease.
Sentinel surveillance system for early outbreak detection in Madagascar
Authors: Randrianasolo Laurence , Raoelina Yolande , Ratsitorahina Maherisoa , Ravolomanana Lisette , Andriamandimby Soa , Heraud Jean-Michel , Rakotomanana Fanjasoa , Ramanjato Robinson , Randrianarivo-Solofoniaina Armand Eugène , Richard Vincent
Published: January 2010

Background

Following the outbreak of chikungunya in the Indian Ocean, the Ministry of Health directed the necessary development of an early outbreak detection system. A disease surveillance team including the Institut Pasteur in Madagascar (IPM) was organized to establish a sentinel syndromic-based surveillance system. The system, which was set up in March 2007, transmits patient data on a daily basis from the various voluntary general practitioners throughout the six provinces of the country to the IPM. We describe the challenges and steps involved in developing a sentinel surveillance system and the well-timed information it provides for improving public health decision-making.

Methods

Surveillance was based on data collected from sentinel general practitioners (SGP). The SGPs report the sex, age, visit date and time, and symptoms of each new patient weekly, using forms addressed to the management team. However, the system is original in that SGPs also report data at least once a day, from Monday to Friday (number of fever cases, rapid test confirmed malaria, influenza, arboviral syndromes or diarrhoeal disease), by cellular telephone (encrypted message SMS). Information can also be validated by the management team, by mobile phone. This data transmission costs 120 ariary per day, less than US$1 per month.

Results

In 2008, the sentinel surveillance system included 13 health centers, and identified 5 outbreaks. Of the 218,849 visits to SGPs, 12.2% were related to fever syndromes. Of these 26,669 fever cases, 12.3% were related to Dengue-like fever, 11.1% to Influenza-like illness and 9.7% to malaria cases confirmed by a specific rapid diagnostic test.

Conclusion

The sentinel surveillance system represents the first nationwide real-time-like surveillance system ever established in Madagascar. Our findings should encourage other African countries to develop their own syndromic surveillance systems.

Prompt detection of an outbreak of infectious disease may lead to control measures that limit its impact and help prevent future outbreaks.