bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring Perceptions of Health Needs Among Young African American Men
Authors: Marcell Arik V. , Jagers Robert J. , Mayden Bronwyn , Mobley Cynthia
Published: September 2008

Recent recommendations advocate involving young men in reproductive health programs. We know little about how young men perceive their reproductive health needs. For this study, 47 African American young men (mean age, 17.9 years) recruited from four community-based organizations completed a brief survey to explore life priorities and perceptions of health needs across 12 to 14, 15 to 19, and 20 to 25-year-olds. Participants’ life priorities varied by age group with overall top categories, including education, economics, and family members. Health was listed as a salient life priority among older participants aged 15 to 25 years, though it was not highly ranked. Participants’ top health concerns included sexually transmitted infections and HIV/AIDS, with limited mention of other reproductive health concerns. Understanding where young men start from when thinking about reproductive health can better help us meet their needs. Future studies warrant examining how health needs change over time among a larger and more diverse sample of young men.
Decision-making as a Struggle and a Play
Authors: Salo Petri
Published: September 2008

In this article an alternative interpretation of the functions of decision-making and the inherent activities at teachers' meetings at schools are presented. The metaphor of `play' is introduced in order to make the teachers' actions during decision-making comprehensible, not only for outsiders, but more importantly for `involved insiders', such as school leaders. The metaphor of decision-making as a play relies on different theoretical perspectives, mainly on the micropolitical perspective on and dramaturgical approach to schools as organizations. The idea of alternative rationalities is chiefly brought forward in order to understand the behaviour of the teachers involved in decision-making in staff meetings in a more comprehensive manner.
Using Diverse Data to Develop and Sustain School, Family and Community Partnerships
Authors: Sanders Mavis G.
Published: September 2008

This article reports findings from a case study of district leadership for school, family and community partnerships in a suburban district in the mid-Atlantic region of the USA. Analyses suggest that the case district's family and community involvement specialist has been successful in using different kinds of data to achieve a variety of goals that are linked to program growth, improvement, and sustainability. Analyses further suggest that the district specialist has successfully facilitated the collection and use of data among school-based teams for school, family and community partnerships. Her efforts highlight an important district leadership function in an increasingly data-driven educational reform environment.
Imaging of plasmacytoid dendritic cell interactions with T cells
Authors: Mittelbrunn María , del Hoyo Gloria Martínez , López-Bravo María , Martín-Cofreces Noa B. , Scholer Alix , Hugues Stéphanie , Fetler Luc , Amigorena Sebastián , Ardavín Carlos , Sánchez-Madrid Francisco
Published: September 2008

Plasmacytoid dendritic cells (pDCs) efficiently produce type I interferon and participate in adaptive immune responses, although the molecular interactions between pDCs and antigen-specific T cells remain unknown. This study examines immune synapse (IS) formation between murine pDCs and CD4+ T cells. Mature pDCs formed canonical ISs, involving relocation to the contact site of the microtubule-organizing center, F-actin, protein kinase C-θ, and pVav, and activation of early signaling molecules in T cells. However, immature pDCs were less efficient at forming conjugates with T cells and inducing IS formation, microtubule-organizing center translocation, and T-cell signaling and activation. Time-lapse videomicroscopy and 2-photon in vivo imaging of pDC–T-cell interactions revealed that immature pDCs preferentially mediated transient interactions, whereas mature pDCs promoted more stable contacts. Our data indicate that, under steady-state conditions, pDCs preferentially establish transient contacts with naive T cells and show a very modest immunogenic capability, whereas on maturation, pDCs are able to form long-lived contacts with T cells and significantly enhance their capacity to activate these lymphocytes.
Stable transduction of quiescent T cells without induction of cycle progression by a novel lentiviral vector pseudotyped with measles virus glycoproteins
Authors: Frecha Cecilia , Costa Caroline , Nègre Didier , Gauthier Emmanuel , Russell Stephen J. , Cosset François-Loïc , Verhoeyen Els
Published: September 2008

A major limitation of current lentiviral vectors (LVs) is their inability to govern efficient gene transfer into quiescent cells such as primary T cells, which hampers their application for gene therapy. Here we generated high-titer LVs incorporating Edmonston measles virus (MV) glycoproteins H and F on their surface. They allowed efficient transduction through the MV receptors, SLAM and CD46, both present on blood T cells. Indeed, these H/F-displaying vectors outperformed by far VSV-G-LVs for the transduction of IL-7–prestimulated T cells. More importantly, a single exposure to these H/F-LVs allowed efficient gene transfer in quiescent T cells, which are not permissive for VSV-G-LVs that need cell-cycle entry into the G1b phase for efficient transduction. High-level transduction of resting memory (50%) and naive (11%) T cells with H/F-LVs, which seemed to occur mainly through SLAM, was not at cost of cell-cycle entry or of target T-cell activation. Finally, the naive or memory phenotypes of transduced resting T cells were maintained and no changes in cytokine profiles were detected, suggesting that T-cell populations were not skewed. Thus, H/F-LV transduction of resting T cells overcomes the limitation of current lentiviral vectors and may improve the efficacy of T cell–based gene therapy.
Cyclic AMP plays a critical role in C3a-receptor–mediated regulation of dendritic cells in antigen uptake and T-cell stimulation
Authors: Li Ke , Anderson Katie J. , Peng Qi , Noble Alistair , Lu Bao , Kelly Adrian P. , Wang Naiyin , Sacks Steven H. , Zhou Wuding
Published: September 2008

The biochemical basis for complement acting directly on antigen-presenting cells to enhance their function in T-cell stimulation has been unclear. Here we present evidence that engagement of C3a receptor (C3aR) on the surface of dendritic cells (DCs) leads to alterations in the level of intracellular cyclic adenosine monophosphate (cAMP), a potent negative regulator of inflammatory cytokines. C3aR activation-induced depression of cAMP was associated with enhanced capacity of DCs for antigen uptake and T-cell stimulation. Conversely, C3aR-deficient DCs showed elevation of cAMP and impaired properties for antigen uptake and immune stimulation. Similarities in the phenotype of C3-deficient and C3aR-deficient DCs suggest that local production of C3 with extracellular metabolism to C3a is an important driver of DC alterations in cAMP. The finding of a link between complement and adaptive immune stimulation through cAMP offers new insight into how innate and adaptive immunity combine to generate efficient effector and memory responses.
Chronic lymphocytic leukemia antibodies with a common stereotypic rearrangement recognize nonmuscle myosin heavy chain IIA
Authors: Chu Charles C. , Catera Rosa , Hatzi Katerina , Yan Xiao-Jie , Zhang Lu , Wang Xiao Bo , Fales Henry M. , Allen Steven L. , Kolitz Jonathan E. , Rai Kanti R. , Chiorazzi Nicholas
Published: September 2008

Leukemic B lymphocytes of a large group of unrelated chronic lymphocytic leukemia (CLL) patients express an unmutated heavy chain immunoglobulin variable (V) region encoded by IGHV1-69, IGHD3-16, and IGHJ3 with nearly identical heavy and light chain complementarity-determining region 3 sequences. The likelihood that these patients developed CLL clones with identical antibody V regions randomly is highly improbable and suggests selection by a common antigen. Monoclonal antibodies (mAbs) from this stereotypic subset strongly bind cytoplasmic structures in HEp-2 cells. Therefore, HEp-2 cell extracts were immunoprecipitated with recombinant stereotypic subset-specific CLL mAbs, revealing a major protein band at approximately 225 kDa that was identified by mass spectrometry as nonmuscle myosin heavy chain IIA (MYHIIA). Reactivity of the stereotypic mAbs with MYHIIA was confirmed by Western blot and immunofluorescence colocalization with anti-MYHIIA antibody. Treatments that alter MYHIIA amounts and cytoplasmic localization resulted in a corresponding change in binding to these mAbs. The appearance of MYHIIA on the surface of cells undergoing stress or apoptosis suggests that CLL mAb may generally bind molecules exposed as a consequence of these events. Binding of CLL mAb to MYHIIA could promote the development, survival, and expansion of these leukemic cells.
Central role of Sp1-regulated CD39 in hypoxia/ischemia protection
Authors: Eltzschig Holger K. , Köhler David , Eckle Tobias , Kong Tianqing , Robson Simon C. , Colgan Sean P.
Published: September 2008

Hypoxia is common to several inflammatory diseases, where multiple cell types release adenine-nucleotides (particularly adenosine triphosphate/adenosine diphosphate). Adenosine triphosphate/adenosine diphosphate is metabolized to adenosine through a 2-step enzymatic reaction initiated by CD39 (ectonucleoside-triphosphate-diphosphohydrolase-1). Thus, extracellular adenosine becomes available to regulate multiple inflammatory endpoints. Here, we hypothesized that hypoxia transcriptionally up-regulates CD39 expression. Initial studies revealed hypoxia-dependent increases in CD39 mRNA and immunoreactivity on endothelia. Examination of the human CD39 gene promoter identified a region important in hypoxia inducibility. Multiple levels of analysis, including site-directed mutagenesis, chromatin immunoprecipitation, and inhibition by antisense, revealed a critical role for transcription-factor Sp1 in hypoxia-induction of CD39. Using a combination of cd39−/− mice and Sp1 small interfering RNA in in vivo cardiac ischemia models revealed Sp1-mediated induction of cardiac CD39 during myocardial ischemia. In summary, these results identify a novel Sp1-dependent regulatory pathway for CD39 and indicate the likelihood that CD39 is central to protective responses to hypoxia/ischemia.
FAF-Drugs2: Free ADME/tox filtering tool to assist drug discovery and chemical biology projects
Authors: Lagorce David , Sperandio Olivier , Galons Hervé , Miteva Maria A , Villoutreix Bruno O
Published: September 2008

Background

Drug discovery and chemical biology are exceedingly complex and demanding enterprises. In recent years there are been increasing awareness about the importance of predicting/optimizing the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of small chemical compounds along the search process rather than at the final stages. Fast methods for evaluating ADMET properties of small molecules often involve applying a set of simple empirical rules (educated guesses) and as such, compound collections' property profiling can be performed in silico. Clearly, these rules cannot assess the full complexity of the human body but can provide valuable information and assist decision-making.

Results

This paper presents FAF-Drugs2, a free adaptable tool for ADMET filtering of electronic compound collections. FAF-Drugs2 is a command line utility program (e.g., written in Python) based on the open source chemistry toolkit OpenBabel, which performs various physicochemical calculations, identifies key functional groups, some toxic and unstable molecules/functional groups. In addition to filtered collections, FAF-Drugs2 can provide, via Gnuplot, several distribution diagrams of major physicochemical properties of the screened compound libraries.

Conclusion

We have developed FAF-Drugs2 to facilitate compound collection preparation, prior to (or after) experimental screening or virtual screening computations. Users can select to apply various filtering thresholds and add rules as needed for a given project. As it stands, FAF-Drugs2 implements numerous filtering rules (23 physicochemical rules and 204 substructure searching rules) that can be easily tuned.
A novel reverse transduction adenoviral array for the functional analysis of shRNA libraries
Authors: Oehmig Angelika , Klotzbücher Andrea , Thomas Maria , Weise Frank , Hagner Ursula , Brundiers Ralf , Waldherr Dirk , Lingnau Andreas , Knappik Achim , Kubbutat Michael HG , Joos Thomas O , Volkmer Hansjürgen
Published: September 2008

Background

The identification of novel drug targets by assessing gene functions is most conveniently achieved by high-throughput loss-of-function RNA interference screening. There is a growing need to employ primary cells in such screenings, since they reflect the physiological situation more closely than transformed cell lines do. Highly miniaturized and parallelized approaches as exemplified by reverse transfection or transduction arrays meet these requirements, hence we verified the applicability of an adenoviral microarray for the elucidation of gene functions in primary cells.

Results

Here, we present microarrays of infectious adenoviruses encoding short hairpin RNA (shRNA) as a new tool for gene function analysis. As an example to demonstrate its application, we chose shRNAs directed against seven selected human protein kinases, and we have performed quantitative analysis of phenotypical responses in primary human umbilical vein cells (HUVEC). These microarrays enabled us to infect the target cells in a parallelized and miniaturized procedure without significant cross-contamination: Viruses were reversibly immobilized in spots in such a way that the seeded cells were confined to the area of the viral spots, thus simplifying the subsequent addressing of genetically modified cells for analysis. Computer-assisted image analysis of fluorescence images was applied to analyze the cellular response after shRNA expression. Both the expression level of knock-down target proteins as well as the functional output as measured by caspase 3 activity and DNA fractionation (TUNEL) were quantified.

Conclusion

We have developed an adenoviral microarray technique suitable for miniaturized and parallelized analysis of gene function. The practicability of this technique was demonstrated by the analysis of several kinases involved in the activation of programmed cell death, both in tumor cells and in primary cells.
Determination of the efficacy and side-effect profile of lower doses of intrathecal morphine in patients undergoing total knee arthroplasty
Authors: Hassett Patrick , Ansari Bilal , Gnanamoorthy Pachaimuthu , Kinirons Brian , Laffey John G
Published: September 2008

Background

Intrathecal (IT) morphine provides excellent post-operative analgesia, but causes multiple side effects including nausea and vomiting (PONV), pruritus and respiratory depression, particularly at higher doses. The lowest effective dose of spinal morphine in patients undergoing total knee arthroplasty is not known.

Methods

We evaluated the analgesic efficacy and side effect profile of 100 – 300 μg IT morphine in patients undergoing elective total knee replacement in this prospective, randomized, controlled, double-blind study. Sixty patients over the age of 60 undergoing elective knee arthroplasty were enrolled. Patients were randomized to receive spinal anaesthesia with 15 mg Bupivacaine and IT morphine in three groups: (i) 100 μg; (ii) 200 μg; and (iii) 300 μg.

Results

Both 200 μg and 300 μg IT morphine provided comparable levels of postoperative analgesia. However, patients that received 100 μg had greater pain postoperatively, with higher pain scores and a greater requirement for supplemental morphine. There were no differences between groups with regard to PONV, pruritus, sedation, respiratory depression or urinary retention.

Conclusion

Both 200 μg and 300 μg provided comparable postoperative analgesia, which was superior to that provided by 100 μg IT morphine in patients undergoing total knee arthroplasty. Based on these findings, we recommend that 200 μg IT morphine be used in these patients.

Trial registration

ClinicalTrials.gov Identifier NCT00695045
The role of polyclonal intravenous immunoglobulin in treating HIV-infected children with severe bacterial infections: A retrospective cohort study
Authors: Huang Lyen C , Myer Landon , Jaspan Heather B
Published: September 2008

Background

Mortality among HIV-infected children in developing countries remains high after serious bacterial infections despite the use of antibiotics. Intravenous immunoglobulin (IVIG) has been used as an adjuvant therapy to treat these infections, but little data exists regarding its efficacy, and previous studies have focused on IVIG as a prophylactic agent. We examined the impact of IVIG as an adjuvant therapy in reducing mortality and length of hospital stay in HIV-infected children with serious bacterial infections.

Methods

This retrospective study focused on pediatric admissions at a large urban hospital between 2002 and 2006. Children between the ages of one month and nine years of age with laboratory confirmed HIV-status, serious bacterial infection, no prior exposure to IVIG, and a hospital length of stay of 5 days or more, were eligible for inclusion.

Results

A total of 140 children (median age 1.2 years) met inclusion criteria; lower respiratory tract infection was diagnosed in 94 (67%) of the children, while 74 (53%) had bacterial sepsis. Fifty-four (39%) children were receiving antiretroviral therapy and 39 (28%) were receiving tuberculosis treatment. Overall 73 (52%) were treated with IVIG, with the majority (74%) of children receiving a single dose. Thirteen (9%) died during their hospital admission. In crude analysis IVIG was significantly associated with increased mortality was (Odds Ratio (OR): 5.8; 95% Confidence Interval (CI): 1.2–27.1) and this association was weakened by adjustment for other predictors of mortality (OR 4.3, 95% CI 0.7–27.9, p = 0.123). IVIG use was also associated with longer hospital stays.

Conclusion

Administration of one to three doses of IVIG during the acute phase of illness does not appear to reduce mortality or the length of hospital stays in HIV-infected children with serious bacterial infections. However, the retrospective nature of this study makes confounding by indication difficult to control and further studies regarding the timing, dosing, and method of administration are required. Nonetheless the routine use of IVIG in resource-limited settings should be carefully considered given its high cost.
Pattern of humoral immune response to Plasmodium falciparum blood stages in individuals presenting different clinical expressions of malaria
Authors: Leoratti Fabiana MS , Durlacher Rui R , Lacerda Marcus VG , Alecrim Maria G , Ferreira Antonio W , Sanchez Maria CA , Moraes Sandra L
Published: September 2008

Background

The development of protective immunity against malaria is slow and to be maintained, it requires exposure to multiple antigenic variants of malaria parasites and age-associated maturation of the immune system. Evidence that the protective immunity is associated with different classes and subclasses of antibodies reveals the importance of considering the quality of the response. In this study, we have evaluated the humoral immune response againstPlasmodium falciparumblood stages of individuals naturally exposed to malaria who live in endemic areas of Brazil in order to assess the prevalence of different specific isotypes and their association with different malaria clinical expressions.

Methods

Different isotypes againstP. falciparumblood stages, IgG, IgG1, IgG2, IgG3, IgG4, IgM, IgE and IgA, were determined by ELISA. The results were based on the analysis of different clinical expressions of malaria (complicated, uncomplicated and asymptomatic) and factors related to prior malaria exposure such as age and the number of previous clinical malaria attacks. The occurrence of the H131 polymorphism of the FcγIIA receptor was also investigated in part of the studied population.

Results

The highest levels of IgG, IgG1, IgG2 and IgG3 antibodies were observed in individuals with asymptomatic and uncomplicated malaria, while highest levels of IgG4, IgE and IgM antibodies were predominant among individuals with complicated malaria. Individuals reporting more than five previous clinical malaria attacks presented a predominance of IgG1, IgG2 and IgG3 antibodies, while IgM, IgA and IgE antibodies predominated among individuals reporting five or less previous clinical malaria attacks. Among individuals with uncomplicated and asymptomatic malaria, there was a predominance of high-avidity IgG, IgG1, IgG2 antibodies and low-avidity IgG3 antibodies. The H131 polymorphism was found in 44.4% of the individuals, and the highest IgG2 levels were observed among asymptomatic individuals with this allele, suggesting the protective role of IgG2 in this population.

Conclusion

Together, the results suggest a differential regulation in the anti-P. falciparumantibody pattern in different clinical expressions of malaria and showed that even in unstable transmission areas, protective immunity against malaria can be observed, when the appropriated antibodies are produced.
Comprehensive study of proteasome inhibitors against Plasmodium falciparum laboratory strains and field isolates from Gabon
Authors: Kreidenweiss Andrea , Kremsner Peter G , Mordmüller Benjamin
Published: September 2008

Background

The emergence and spread of Plasmodium falciparum resistance to almost all available antimalarial drugs necessitates the search for new chemotherapeutic compounds. The ubiquitin/proteasome system plays a major role in overall protein turnover, especially in fast dividing eukaryotic cells including plasmodia. Previous studies show that the 20S proteasome is expressed and catalytically active in plasmodia and treatment with proteasome inhibitors arrests parasite growth. This is the first comprehensive screening of proteasome inhibitors with different chemical modes of action against laboratory strains of P. falciparum. Subsequently, a selection of inhibitors was tested in field isolates from Lambaréné, Gabon.

Methods

Epoxomicin, YU101, YU102, MG132, MG115, Z-L3-VS, Ada-Ahx3-L3-VS, lactacystin, bortezomib (Velcade®), gliotoxin, PR11 and PR39 were tested and compared to chloroquine- and artesunate-activities in a standardized in vitro drug susceptibility assay against P. falciparum laboratory strains 3D7, D10 and Dd2. Freshly obtained field isolates from Lambaréné, Gabon, were used to measure the activity of chloroquine, artesunate, epoxomicin, MG132, lactacystin and bortezomib. Parasite growth was detected through histidine-rich protein 2 (HRP2) production. Raw data were fitted by a four-parameter logistic model and individual inhibitory concentrations (50%, 90%, and 99%) were calculated.

Results

Amongst all proteasome inhibitors tested, epoxomicin showed the highest activity in chloroquine-susceptible (IC50: 6.8 nM [3D7], 1.7 nM [D10]) and in chloroquine-resistant laboratory strains (IC50: 10.4 nM [Dd2]) as well as in field isolates (IC50: 8.5 nM). The comparator drug artesunate was even more active (IC50: 1.0 nM), whereas all strains were chloroquine-resistant (IC50: 113 nM).

Conclusion

The peptide α',β'-epoxyketone epoxomicin is highly active against P. falciparum regardless the grade of the parasite's chloroquine susceptibility. Therefore, inhibition of the proteasome is a highly promising strategy to develop new antimalarials. Epoxomicin can serve as a standard to compare new inhibitors with species-specific activity.
Child-OIDP index in Brazil: Cross-cultural adaptation and validation
Authors: Castro Rodolfo AL , Cortes Maria IS , Leão Anna T , Portela Margareth C , Souza Ivete PR , Tsakos Georgios , Marcenes Wagner , Sheiham Aubrey
Published: September 2008

Background

Oral health-related quality of life (OHRQoL) measures are being increasingly used to introduce dimensions excluded by normative measures. Consequently, there is a need for an index which evaluates children's OHRQoL validated for Brazilian population, useful for oral health needs assessments and for the evaluation of oral health programs, services and technologies. The aim of this study was to do a cross-cultural adaptation of the Child Oral Impacts on Daily Performances (Child-OIDP) index, and assess its reliability and validity for application among Brazilian children between the ages of eleven and fourteen.

Methods

For cross-cultural adaptation, a translation/back-translation method integrated with expert panel reviews was applied. A total of 342 students from four public schools took part of the study.

Results

Overall, 80.7% of the sample reported at least one oral impact in the last three months. Cronbach's alpha was 0.63, the weighted kappa 0.76, and the intraclass correlation coefficient (ICC) 0.79. The index had a significant association with self-reported health measurements (self-rated oral health, satisfaction with oral health, perceived dental treatment needs, self-rated general health; all p < 0.01).

Conclusion

It was concluded that the Child-OIDP index is a measure of oral health-related quality of life that can be applied to Brazilian children.
Fatigue testing of three peristernal median sternotomy closure techniques
Authors: Wangsgard Cameron , Cohen David J , Griffin Lanny V
Published: September 2008

Background

Failure of a sternotomy closure because of closure system fatigue is a complication that may result in dehiscence and put the individual at risk for serious complications. The purpose of this study was to assess the fatigue performance of three peristernal median sternotomy closure techniques (figure-of-eight stainless-steel wires, figure-of-eight stainless-steel cables, or Pectofix Dynamic Sternal Fixation [DSF] stainless-steel plates) in order to quantify the potential risk of fatigue failure of these devices when subject to cyclic loads in physiologically relevant loading directions.

Study Design

All tests were conducted on polyurethane foam sternal models. A cardiothoracic surgeon divided each sternal model longitudinally and repaired it with a closure device. Tests were performed using a materials testing system that applied cyclic loading in a uniaxial direction until the test model catastrophically broke or data run-out occurred. For each loading direction (lateral distraction and longitudinal shear), five trials of each closure technique were tested. Life data and location of device failure (if present) were evaluated. Statistical analysis was performed using regression with life data allowed for correlation between life data and the various closure techniques to develop risk assessment curves for each device.

Results

The data show that the figure-of-eight stainless-steel cable and the DSF plate systems are considerably less likely to fail under both lateral distraction and longitudinal shear cyclic loading conditions as compared to the figure-of-eight stainless-steel wire system. Moreover, the figure-of-eight stainless-steel cable system is the most resistant to failure, particularly for high cycle counts.

Conclusion

This study in addition to Cohen and Griffin's earlier published biomechanical comparison of the ultimate strength of these same three closure techniques provide extensive experimental evidence regarding the mechanical differences among these three peristernal median sternotomy closure techniques. All data support the hypothesis that both the DSF plate system and the stainless-steel cable system offer important advantages over figure-of-eight wire closure techniques; although twisted wires are the weak-link in the systems we tested.
Tv-RIO1 – an atypical protein kinase from the parasitic nematode Trichostrongylus vitrinus
Authors: Hu Min , LaRonde-LeBlanc Nicole , Sternberg Paul W , Gasser Robin B
Published: September 2008

Background

Protein kinases are key enzymes that regulate a wide range of cellular processes, including cell-cycle progression, transcription, DNA replication and metabolic functions. These enzymes catalyse the transfer of phosphates to serine, threonine and tyrosine residues, thus playing functional roles in reversible protein phosphorylation. There are two main groups, namely eukaryotic protein kinases (ePKs) and atypical protein kinases (aPKs); RIO kinases belong to the latter group. While there is some information about RIO kinases and their roles in animals, nothing is known about them in parasites. This is the first study to characterise a RIO1 kinase from any parasite.

Results

A full-length cDNA (Tv-rio-1) encoding a RIO1 protein kinase (Tv-RIO1) was isolated from the economically important parasitic nematode Trichostrongylus vitrinus (Order Strongylida). The uninterrupted open reading frame (ORF) of 1476 nucleotides encoded a protein of 491 amino acids, containing the characteristic RIO1 motif LVHADLSEYNTL. Tv-rio-1 was transcribed at the highest level in the third-stage larva (L3), and a higher level in adult females than in males. Comparison with homologues from other organisms showed that protein Tv-RIO1 had significant homology to related proteins from a range of metazoans and plants. Amino acid sequence identity was most pronounced in the ATP-binding motif, active site and metal binding loop. Phylogenetic analyses of selected amino acid sequence data revealed Tv-RIO1 to be most closely related to the proteins in the species of Caenorhabditis. A structural model of Tv-RIO1 was constructed and compared with the published crystal structure of RIO1 of Archaeoglobus fulgidus (Af-Rio1).

Conclusion

This study provides the first insights into the RIO1 protein kinases of nematodes, and a foundation for further investigations into the biochemical and functional roles of this molecule in biological processes in parasitic nematodes.
Trial femoral head loss in to the soft tissues of pelvis during primary total hip replacement: a case report
Authors: Vertelis Arunas , Vertelis Linas , Tarasevicius Sarunas
Published: September 2008

The loss of trial femoral head in the soft tissues is a rare per operative complication in total hips replacement. We report the loss of the femoral head in surrounding hip joint soft tissues and unsuccessful attempts to locate and remove it. Surgeons should be aware of such complication as trial femoral heads usually are made from non radiolucent material and cannot be detected by regular x-ray examination during surgery. The industry should consider manufacturing trial femoral heads from x-ray visible material.
Dynamic activation of bone morphogenetic protein signaling in collagen-induced arthritis supports their role in joint homeostasis and disease
Authors: Daans Melina , Lories Rik JU , Luyten Frank P
Published: September 2008

Introduction

Rheumatoid arthritis is a chronic systemic autoimmune disease affecting peripheral joints and leading to loss of joint function. The severity and outcome of disease are dependent on the balance between inflammatory/destructive and homeostatic or repair pathways. Increasing evidence suggests a role for bone morphogenetic protein (BMP) signaling in joint homeostasis and disease.

Methods

Activation of BMP signaling in collagen-induced arthritis as a model of rheumatoid arthritis was studied by immunohistochemistry and Western blot for phosphorylated SMAD1/5 at different time points. Expression of different BMP ligands and noggin, a BMP antagonist, was determined on synovium and cartilage extracts of arthritic knees, at different time points, with quantitative polymerase chain reaction. At the protein level, BMP2 and BMP7 were studied with immunohistochemistry. Finally, the effect of anti-tumor necrosis factor-alpha (TNFα) treatment on the expression of BMP2, BMP7, and growth and differentiation factor-5 (GDF5) in synovium and cartilage of arthritic knees was investigated.

Results

A time-dependent activation of the BMP signaling pathway in collagen-induced arthritis was demonstrated with a dynamic and characteristic expression pattern of different BMP subfamily members in synovium and cartilage of arthritic knees. As severity increases, the activation of BMP signaling becomes more prominent in the invasive pannus tissue. BMP2 is present in cartilage and the hyperplastic lining layer. BMP7 is found in the sublining zone and inflammatory infiltrate. Treatment with etanercept slowed down progression of disease, but no change in expression of GDF5, BMP2, and BMP7 in synovium was found; in the cartilage, however, blocking of TNFα increased the expression of BMP7.

Conclusions

BMP signaling is dynamically activated in collagen-induced arthritis and is partly TNFα-independent. TNFα blocking increased the expression of BMP7 in the articular cartilage, possibly enhancing anabolic mechanisms. Different types of source and target cells are recognized. These data further support a role for BMP signaling in arthritis.
Menopause, postmenopausal hormone use and serum uric acid levels in US women – The Third National Health and Nutrition Examination Survey
Authors: Hak A Elisabeth , Choi Hyon K
Published: September 2008

Introduction

Despite the substantial prevalence of gout in the ageing female population, female hormonal influence has not been comprehensively examined. We evaluated and quantified the potential independent association between menopause, postmenopausal hormone use and serum uric acid levels in a nationally representative sample of women.

Methods

Using data from 7662 women aged 20 years and older in the Third National Health and Nutrition Examination Survey (1988 to 1994), we examined the relation between menopause, postmenopausal hormone use and serum uric acid levels. We used multivariate linear regression to adjust for other risk factors for hyperuricaemia such as dietary factors, age, adiposity, alcohol use, renal function, hypertension and diuretic use.

Results

Menopause was associated with higher serum uric acid levels. After adjusting for covariates, serum uric acid levels among women with natural menopause and surgical menopause were greater than premenopausal women by 0.34 mg/dl (95% confidence interval [CI], 0.19 to 0.49) and 0.36 mg/dl (95% CI, 0.14 to 0.57), respectively. Current postmenopausal hormone use was associated with a lower serum uric acid level among postmenopausal women (multivariate difference, 0.24 mg/dl [95% CI, 0.11 to 0.36]). The serum uric acid levels increased with increasing age categories (crude difference between 20 to 29 years and 70 years and over = 1.03 mg/dl, p for trend < 0.001), but this increase was not present after adjusting for other covariates (p for trend = 0.66).

Conclusions

These findings from a nationally representative sample of US women indicate that menopause is independently associated with higher serum uric acid levels, whereas postmenopausal hormone use is associated with lower uric acid levels among postmenopausal women. The age-associated increase in serum uric acid levels in women may be explained by menopause and other age-related factors.
Dickkopf-Like1 Regulates Postpubertal Spermatocyte Apoptosis and Testosterone Production
Authors: Dakhova Olga , O'Day Diana , Kinet Noe , Yucer Nur , Wiese Mary , Shetty Gunapala , Ducy Patricia
Published: September 2008

Dickkopf-like1 (Dkkl1) encodes a glycoprotein secreted by postmeiotic male germ cells. We report here that adult Dkkl1-deficient males have elevated sperm counts caused by a decrease in postpubertal spermatocyte apoptosis and display, upon aging, increased local production of testosterone. Molecular analyses identified the Fas death ligand (FasL) as a target for Dkkl1 pro-apoptotic activity in adult mice. Accordingly, adult FasL-deficient gld mice display an increased sperm count and decreased spermatocyte apoptosis phenotype similar to the one observed in Dkkl1-deficient mice. We also show that the elevated testosterone level observed in aging Dkkl1-deficient males is secondary to increased expression in Leydig cells of CYP11A and CYP17, two genes implicated in steroidogenesis. Furthermore, treatment of Leydig cells with Dkkl1 decreases DNA binding and transcriptional activity of steroidogenic factor 1, a pivotal regulator of gene expression in testis. Thus, this study establishes Dkkl1 as a negative regulator of adult testis homeostasis and identifies a novel, Dkkl1/FasL-dependent, regulation that specifically controls the number of postpubertal spermatocytes.

Dickkopf-like 1 negatively regulates adult testis biology by promoting spermatocyte apoptosis via Fas ligand activation and by limiting testosterone synthesis in Leydig cells.
Prospective Study of High-Dose Cabergoline Treatment of Prolactinomas in 150 Patients
Authors: Ono Masami , Miki Nobuhiro , Kawamata Takakazu , Makino Rena , Amano Kosaku , Seki Toshiro , Kubo Osami , Hori Tomokatsu , Takano Kazue
Published: September 2008

Context: Cabergoline fails to normalize hyperprolactinemia in a considerable proportion of prolactinomas, especially macroadenomas.

Objective: We examined the effect of individualized high-dose cabergoline treatment on hyperprolactinemia in prolactinomas.

Patients: The study included 122 women and 28 men (93 microadenomas and 57 macroadenomas). Forty-seven had undergone transsphenoidal surgery. According to the preceding medical treatment, the participants were separated into untreated (group U; n = 60), intolerant (group I; n = 64), and resistant (group R; n = 26) groups.

Interventions: We promptly increased cabergoline dose on the basis of individual prolactin levels. Length of treatment was 1 yr.

Results: Cabergoline normalized hyperprolactinemia in all patients except one. The proportion of prolactin normalization in both groups U and I was 83% at 3 months and 95% at 6 months. By contrast, that in group R was 35% at 3 months and 58% at 6 months. Mean cabergoline dose in milligrams per week at the time of prolactin normalization was 2.0 ± 0.3 in group U, 0.9 ± 0.1 in group I, and 5.2 ± 0.6 in group R. Prolactin normalization rate at the 3 mg/wk dose was 84% overall but only 35% in group R. Serum progesterone or testosterone levels, diminished in 122 women or 16 men, respectively, were recovered in all except one resistant and four postmenopausal or panhypopituitary patients.

Conclusion: Individualized high-dose cabergoline treatment can normalize hyperprolactinemia and hypogonadism in nearly all prolactinomas irrespective of tumor size or preceding treatments. Hyperprolactinemia could be controlled in poor responders within 1 yr with doses higher than 3 mg/wk.
Ultrasound Screening for Thyroid Carcinoma in Childhood Cancer Survivors: A Case Series
Authors: Brignardello Enrico , Corrias Andrea , Isolato Giuseppe , Palestini Nicola , Cordero di Montezemolo Luca , Fagioli Franca , Boccuzzi Giuseppe
Published: September 2008

Context: Childhood cancer survivors need regular monitoring into young adulthood and beyond, because they are at risk for developing late-onset complications of cancer therapy, including second malignancies.

Objective: This study focuses on the use of thyroid ultrasound to screen for thyroid carcinoma in a population of childhood cancer survivors.

Patients: A total of 129 subjects who had received radiotherapy to the head, neck, or upper thorax for a pediatric cancer were studied in the setting of a long-term follow-up unit.

Design: Thyroid ultrasound usually began 5 yr after radiotherapy and was repeated every third year, if negative. Median follow-up time since childhood cancer diagnosis was 15.8 yr (range 6.1–34.8 yr). Solid thyroid nodules were found in 35 patients. Fine-needle aspiration was performed in 19 patients, of which 14 had nodules above 1 cm.

Main Outcome Measure: The main outcome measure was the finding of not palpable thyroid cancers.

Results: Cytological examination of specimens diagnosed papillary carcinoma in five patients who underwent surgery. The cytological diagnosis of papillary thyroid carcinoma was confirmed in all cases by histological examination. Notably, only two of these patients had palpable nodules; the other three were smaller than 1 cm and were detected only by ultrasound. However, histological examination showed nodal metastases in two of these.

Conclusions: Although ultrasound screening for thyroid cancer in the general population is not cost effective and could lead to unnecessary surgery, due to false positives, we believe that in childhood cancer survivors who received radiotherapy involving the head, neck, or upper thorax, it would be worthwhile.
Cannibals and Crusaders
Authors: Rubenstein Jay
Published: September 2008

During the First Crusade (1095–99) the Franks cannibalized the Muslim dead at the city of Ma`arra. More than a dozen narrative sources describe this act, but with significant differences in detail. Through an examination of the different accounts and of the probable historical, biblical, and literary models used to shape them, this article suggests that cannibalism was in part a product of necessity but also that the crusaders used it as a tool of psychological warfare. Their status as God's warriors and their project of holy war both justified and inspired such tactics. The article thus questions the direction of current scholarship, which sees the First Crusade as a result of ordinary medieval practices of warfare and piety, rather than as an unprecedented event as disconcerting to medieval sensibilities as to modern ones.

Durant la Première Croisade (1095–99) les Francs se nourrirent de la chair des Musulmans morts à la ville de Ma`arra. Ce fait est attesté par plus d'une douzaine de sources, mais dont les détails diffèrent significativement. A travers l'examen des différents comptes rendus ainsi que des probables modèles historiques, bibliques et littéraires qui les ont inspirés, cet article suggère que le cannibalisme fut en partie causé par la nécessité, mais aussi que les croisés en firent également un outil de guerre psychologique. Leur qualité de combattants de Dieu comme leur projet de guerre sainte justifiaient et inspiraient de telles tactiques. L'article questionne ainsi l'historiographie qui voit la Première Croisade comme le produit des pratiques médiévales ordinaires de guerre et de piété davantage que comme un événement exceptionnel et troublant pour les hommes médiévaux ainsi que pour les modernes.
Shades of Fraternity: Creolization and the Making of Citizenship in French India, 1790–1792
Authors: Carton Adrian
Published: September 2008

On October 16, 1790, a group of topas men wrote a petition to the Colonial Assembly at Pondichéry, protesting the decision of September that year to exclude them from the electoral list of active citizens on the basis of “race.” These propertied, free men of color demanded to have the same rights as Europeans and the métis. While historians of the French empire have long considered how mulatto and creole people in the French Caribbean negotiated the boundaries of citizenship after the Revolution, the debate that emerged in India offers a different view. This essay argues that the topas drew on precedents from other French colonies, as well as on the status of foreigners in France itself, to argue that domicile (ius solis) rather than bloodline (ius sanguinis) formed the basis of what it meant to be French. Hence skin color could not be a barrier to citizenship rights.

Le 16 octobre 1790, un groupe d'hommes topas ont rédigé une pétition adressée à l'Assemblée coloniale de Pondichéry pour protester contre une décision prise au mois de septembre de la même année visant à les exclure de la liste électorale des citoyens actifs en raison de leur « race ». Ces hommes de couleur libres et propriétaires ont exigé les mêmes droits que les Européens et les métis. Tandis que les historiens de l'empire français se penchent depuis longtemps sur la manière dont les mulâtres et les créoles ont négocié les frontières de la citoyenneté aux Caraïbes français après la Révolution, le débat suscité en Inde offre une vue différente. Cet essai soutient que les topas se sont inspirés de précédents dans d'autres colonies françaises ainsi que du statut des étrangers en France elle-même pour affirmer que c'était le « domicile » (ius solis) plutôt que la « lignée » (ius sanguinis) qui constituait la base de ce que voulait dire être français. Ainsi, la couleur de la peau ne pouvait pas être une barrière aux droits liés à la citoyenneté.
Zionism as Colonialism: A Comparative View of Diluted Colonialism in Asia and Africa
Authors: Pappé Ilan
Published: September 2008

This essay compares the Zionist movement with other settler colonialist movements in Palestine and West Africa. The historical context, the formative years, the ideological infrastructure, the symbolic world, and activities on the ground are examined in three cases: the Zionist movement, the Templers' movement, and the Basel Mission. Particular focus is given to the relationship with a mother country or metropole in order to find out how unique the Zionist case study was in the history of colonialism. The comparative approach validates the need to further examine Zionism as a settler colonialist phenomenon, despite its unique origins and chronological timing. This scholarly orientation was shunned for many years and was not properly attempted due to ideological considerations. This essay is an addendum to the important recent attempts by a few critical Israeli sociologists to introduce the paradigm of colonialism into the study of Israel and Zionism.
Naturalizing Cultural Pluralism, Americanizing Zionism: The Settler Colonial Basis to Early-Twentieth-Century Progressive Thought
Authors: Obenzinger Hilton
Published: September 2008

This essay argues that ideological rationales for assimilation or cultural pluralism during the Progressive Era were formulated in close relation to Zionism, asserting the validity of settler colonial societies as vehicles for democratic self-determination while marginalizing native peoples. In the early twentieth century, Horace Kallen, John Dewey, Louis Brandeis, and others attempted to “naturalize” the increasing diversity of (European) immigration to the United States at the same time that they argued for “Americanizing” support for Zionist settlement. Kallen, Dewey, and others articulated “cultural pluralism” as a progressive, humanitarian outlook to embrace the new immigrants; at the same time, these progressive thinkers also argued that persecuted European Jews deserved a homeland, which in turn would allow for a national identity from which Jews could participate in a pluralist society in the United States. For these thinkers, advocating a Jewish homeland in fact followed American democratic principles, and they drew parallels with Puritan Hebraism and frontier settlement as sources for democratic equality. The dual process to “naturalize” Zionism and to “Americanize” immigrants arose from two different stages of colonial settlement and took place against the background of the rise of the United States as a world imperial power. While most of these thinkers advanced more inclusive visions of democracy and self-determination than others at the time, their formulations were sharply circumscribed by their acceptance of the color line and their colonialist blindness.