bluuebunny/crossref_metadata_2025 huggingface dataset:
Berberine enhances inhibition of glioma tumor cell migration and invasiveness mediated by arsenic trioxide
Authors: Lin Tseng-Hsi , Kuo Hsing-Chun , Chou Fen-Pi , Lu Fung-Jou
Published: February 2008

Background

Arsenic trioxide (As2O3) exhibits promising anticarcinogenic activity in acute promyelocytic leukemic patients and induces apoptosis in various tumor cellsin vitro. Here, we investigated the effect of the natural alkaloid berberine on As2O3-mediated inhibition of cancer cell migration using rat and human glioma cell lines.

Methods

The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to determine the viability of rat C6 and human U-87 glioma cells after treatment with As2O3or berberine, and after co-treatment with As2O3and berberine. The wound scratch and Boyden chamber assays were applied to determine the effect of As2O3and berberine on the migration capacity and invasiveness of glioma cancer cells. Zymography and Western blot analyses provided information on the effect of As2O3and berberine on the intracellular translocation and activation of protein kinase C (PKC), and some PKC-related downstream factors. Most assays were performed three times, independently, and data were analyzed using ANOVA.

Results

The cell viability studies demonstrated that berberine enhances As2O3-mediated inhibition of glioma cell growth after 24 h incubation. Untreated control cells formed a confluent layer, the formation of which was inhibited upon incubation with 5 μM As2O3. The latter effect was even more pronounced in the presence of 10 μM berberine. The As2O3-mediated reduction in motility and invasion of glioma cells was enhanced upon co-treatment with berberine. Furthermore, it has been reported that PKC isoforms influence the morphology of the actin cytoskeleton, as well as the activation of metalloproteases MT1-MMP and MMP-2, reported to be involved in cancer cell migration. Treatment of glioma cells with As2O3and berberine significantly decreased the activation of PKC α and ε and led to actin cytoskeleton rearrangements. The levels of two downstream transcription factors, myc and jun, and MT1-MMP and MMP-2 were also significantly reduced.

Conclusion

Upon co-treatment of glioma cells with As2O3and berberine, cancer cell metastasis can be significantly inhibited, most likely by blocking the PKC-mediated signaling pathway involved in cancer cell migration. This study is potentially interesting for the development of novel chemotherapeutic approaches in the treatment of malignant gliomas and cancer development in general.
Detection of methylation in promoter sequences by melting curve analysis-based semiquantitative real time PCR
Authors: Lorente Aiala , Mueller Wolf , Urdangarín Edurne , Lázcoz Paula , von Deimling Andreas , Castresana Javier S
Published: February 2008

Background

We present two melting curve analysis (MCA)-based semiquantitative real time PCR techniques to detect the promoter methylation status of genes. The first, MCA-MSP, follows the same principle as standard MSP but it is performed in a real time thermalcycler with results being visualized in a melting curve. The second, MCA-Meth, uses a single pair of primers designed with no CpGs in its sequence. These primers amplify both unmethylated and methylated sequences. In clinical applications the MSP technique has revolutionized methylation detection by simplifying the analysis to a PCR-based protocol. MCA-analysis based techniques may be able to further improve and simplify methylation analyses by reducing starting DNA amounts, by introducing an all-in-one tube reaction and by eliminating a final gel stage for visualization of the result. The current study aimed at investigating the feasibility of both MCA-MSP and MCA-Meth in the analysis of promoter methylation, and at defining potential advantages and shortcomings in comparison to currently implemented techniques, i.e. bisulfite sequencing and standard MSP.

Methods

The promoters of the RASSF1A (3p21.3), BLU (3p21.3) and MGMT (10q26) genes were analyzed by MCA-MSP and MCA-Meth in 13 astrocytoma samples, 6 high grade glioma cell lines and 4 neuroblastoma cell lines. The data were compared with standard MSP and validated by bisulfite sequencing.

Results

Both, MCA-MSP and MCA-Meth, successfully determined promoter methylation. MCA-MSP provided information similar to standard MSP analyses. However the analysis was possible in a single tube and avoided the gel stage. MCA-Meth proved to be useful in samples with intermediate methylation status, reflected by a melting curve position shift in dependence on methylation extent.

Conclusion

We propose MCA-MSP and MCA-Meth as alternative or supplementary techniques to MSP or bisulfite sequencing.
Neoadjuvant letrozole in postmenopausal estrogen and/or progesterone receptor positive breast cancer: A phase IIb/III trial to investigate optimal duration of preoperative endocrine therapy
Authors: Krainick-Strobel Ute E , Lichtenegger Werner , Wallwiener Diethelm , Tulusan Augustinus H , Jänicke Fritz , Bastert Gunther , Kiesel Ludwig , Wackwitz Birgit , Paepke Stefan
Published: February 2008

Background

In recent years, preoperative volume reduction of locally advanced breast cancers, resulting in higher rates of breast-conserving surgery (BCS), has become increasingly important also in postmenopausal women. Clinical interest has come to center on the third-generation nonsteroidal aromatase inhibitors (AIs), including letrozole, for such neoadjuvant endocrine treatment. This usually lasts 3–4 months and has been extended to up to 12 months, but optimal treatment duration has not been fully established.

Methods

This study was designed as a multicenter, open-label, single-arm, exploratory phase IIb/III clinical trial of letrozole 2.5 mg, one tablet daily, for 4–8 months. The primary objective was to investigate the effect of neoadjuvant treatment duration on tumor regression and BCS eligibility to identify optimal treatment duration. Tumor regression (by clinical examination, mammography, and ultrasound), shift towards BCS eligibility, and safety assessments were the main outcome measures. Standard parametric and nonparametric descriptive statistics were performed.

Results

Letrozole treatment was received by 32 of the enrolled 33 postmenopausal women (median (range): 67.0 (56–85) years) with unilateral, initially BCS-ineligible primary breast cancer (clinical stage ≥ T2, N0, M0). Letrozole treatment duration in the modified intent-to-treat (ITT; required 4 months' letrozole treatment) analysis population (29 patients) was 4 months in 14 patients and > 4 months in 15 patients. The respective per-protocol (PP) subgroup sizes were 14 and 11. The majority of partial or complete responses were observed at 4 months, though some beneficial responses occurred during prolonged letrozole treatment. Compared with baseline, median tumor size in the ITT population was reduced by 62.5% at Month 4 and by 70.0% at final study visit (Individual End). Similarly, in the PP population, respective reductions were 64.0% and 67.0%. Whereas initially all patients were mastectomy candidates, letrozole treatment enabled BCS (lumpectomy) in 22 ITT (75.9%) and 18 PP (72.0%) patients.

Conclusion

Over half of patients become BCS-eligible within 4 months of preoperative letrozole treatment. While prolonged treatment for up to 8 months can result in further tumor volume reduction in some patients, there is no clear optimum for treatment duration. Letrozole has a favorable overall safety and tolerability profile.

Trial registration

ClinicalTrials.gov identifier NCT00535418.
Rosiglitazone but not losartan prevents Nrf-2 dependent CD36 gene expression up-regulation in an in vivo atherosclerosis model
Authors: Hernandez-Trujillo Y , Rodriguez-Esparragon F , Macias-Reyes A , Caballero-Hidalgo A , Rodriguez-Perez Jose C
Published: February 2008

Background

Thiazolidinediones exert anti-inflammatory and anti-oxidative roles and attenuate atherosclerosis by mechanisms partially independent of their metabolizing actions. High doses of angiotensin type 1 receptor (AT1R) blocker losartan (LST) seem to promote fat cell formation by preserving PPARγ activity.

Methods

C57BL/6J diet-induced atherosclerotic susceptible mice randomly received a normal or a high-fat high-cholesterol (HFHC) diet and were treated with rosiglitazone (RG), LST or a vehicle for 12 weeks.

Results

HFHC was associated with increased PPARγ gene expression without an over regulation of PPARγ responsive genes, whereas RG and LST treatments were found to maintain PPARγ activity without resulting in increased PPARγ gene expression. A better anti-inflammatory and antioxidant profile in mice treated with RG regarding LST was observed in spite of a similar PPARγ preserved activity. Chromatin immunoprecipitation (ChIP) assays revealed that animals under HFHC diet treated with RG showed a significant nuclear factor erythroid 2-like 2 (Nrf2)-dependent down-regulation of the expression of the CD36 gene.

Conclusion

The PPARγ agonist RG exerts antioxidant properties that significantly reduced Nrf-2-dependent CD-36 up-regulation in mice under HFHC diet. Because LST treatment was also associated with a preserved PPARγ activity, our data suggests that these RG antioxidant effects are partially independent of its PPARγ metabolizing properties.
Malaria in rural Mozambique. Part II: children admitted to hospital
Authors: Bassat Quique , Guinovart Caterina , Sigaúque Betuel , Aide Pedro , Sacarlal Jahit , Nhampossa Tacilta , Bardají Azucena , Nhacolo Ariel , Macete Eusébio , Mandomando Inácio , Aponte John J , Menéndez Clara , Alonso Pedro L
Published: February 2008

Background

Characterization of severe malaria cases on arrival to hospital may lead to early recognition and improved management. Minimum community based-incidence rates (MCBIRs) complement hospital data, describing the malaria burden in the community.

Methods

A retrospective analysis of all admitted malaria cases to a Mozambican rural hospital between June 2003 and May 2005 was conducted. Prevalence and case fatality rates (CFR) for each sign and symptom were calculated. Logistic regression was used to identify variables which were independent risk factors for death. MCBIRs for malaria and severe malaria were calculated using data from the Demographic Surveillance System.

Results

Almost half of the 8,311 patients admitted during the study period had malaria and 13,2% had severe malaria. Children under two years accounted for almost 60% of all malaria cases. CFR for malaria was 1.6% and for severe malaria 4.4%. Almost 19% of all paediatric hospital deaths were due to malaria. Prostration (55.0%), respiratory distress (41.1%) and severe anaemia (17.3%) were the most prevalent signs among severe malaria cases. Severe anaemia and inability to look for mother's breast were independent risk factors for death in infants younger than eight months. For children aged eight months to four years, the risk factors were malnutrition, hypoglycaemia, chest indrawing, inability to sit and a history of vomiting.

MCBIRs for severe malaria cases were highest in children aged six months to two years of age. MCBIRs for severe malaria per 1,000 child years at risk for the whole study period were 27 in infants, 23 in children aged 1 to <5 years and two in children aged ≥5 years.

Conclusion

Malaria remains the number one cause of admission in this area of rural Mozambique, predominantly affecting young children, which are also at higher risk of dying. Measures envisaged to protect children during their first two years of life are likely to have a greater impact than at any other age.
Major reduction of malaria morbidity with combined vitamin A and zinc supplementation in young children in Burkina Faso: a randomized double blind trial
Authors: Zeba Augustin N , Sorgho Hermann , Rouamba Noël , Zongo Issiaka , Rouamba Jeremie , Guiguemdë Robert T , Hamer Davidson H , Mokhtar Najat , Ouedraogo Jean-Bosco
Published: February 2008

Background

Vitamin A and zinc are crucial for normal immune function, and may play a synergistic role for reducing the risk of infection including malaria caused by Plasmodium falciparum.

Methods

A randomized, double-blind, placebo-controlled trial of a single dose of 200 000 IU of vitamin A with daily zinc supplementation was done in children of Sourkoudougou village, Burkina Faso. Children aged from 6 to 72 months were randomized to receive a single dose of 200 000 IU of vitamin A plus 10 mg elemental zinc, six days a week (n = 74) or placebo (n = 74) for a period of six months. Cross-sectional surveys were conducted at the beginning and the end of the study, and children were evaluated daily for fever. Microscopic examination of blood smear was done in the case of fever (temperature ≥37.5°C) for malaria parasite detection.

Results

At the end of the study we observed a significant decrease in the prevalence malaria in the supplemented group (34%) compared to the placebo group (3.5%) (p < 0.001). Malaria episodes were lower in the supplemented group (p = 0.029), with a 30.2% reduction of malaria cases (p = 0.025). Time to first malaria episode was longer in the supplemented group (p = 0.015). The supplemented group also had 22% fewer fever episodes than the placebo group (p = 0.030).

Conclusion

These results suggest that combined vitamin A plus zinc supplementation reduces the risk of fever and clinical malaria episodes among children, and thus may play a key role in malaria control strategies for children in Africa.
Mortality and life expectancy of Yokkaichi Asthma patients, Japan: Late effects of air pollution in 1960–70s
Authors: Guo Peng , Yokoyama Kazuhito , Suenaga Masami , Kida Hirotaka
Published: February 2008

Background

The incidence of chronic obstructive pulmonary disease (COPD) and bronchial asthma began increasing in early 1960s in the population of Yokkaichi-city (Mie Prefecture, Japan). The cause of the disease was sulfur oxide air pollution, and it is known as Yokkaichi Asthma. The pollution markedly decreased by the end of 1970s; no new cases have been reported since 1988. This study aimed at examining the late effects of air pollution on the health of Yokkaichi Asthma patients.

Methods

Mortality rate and life expectancy of patients, registered between 1965 and 1988, were investigated from 1975 through 2000.

Results

Mortality rates for COPD and asthma in patients from Yokkaichi-city were significantly higher than in the whole population of Mie Prefecture. For all ages (except for males between 80 and 84 years in 1985), the life expectancy of both males and females were significantly reduced in patients from Yokkaichi-city as compared with the whole population of Mie Prefecture. The potential gains in life expectancy excluding the mortality for respiratory diseases including COPD and asthma were larger for all ages in patients from Yokkaichi-city.

Conclusion

Mortality and life expectancy were adversely affected in patients from Yokkaichi-city, despite the fact that the air pollution problem has been already solved.
Hyperthermic treatment of DMBA-induced rat mammary cancer using magnetic nanoparticles
Authors: Motoyama Jun , Yamashita Noriyuki , Morino Tomio , Tanaka Masashi , Kobayashi Takeshi , Honda Hiroyuki
Published: February 2008

Background

We have developed magnetite cationic liposomes (MCLs) and applied them as a mediator of local hyperthermia. MCLs can generate heat under an alternating magnetic field (AMF). In this study, the in vivo effect of hyperthermia mediated by MCLs was examined using 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary cancer as a spontaneous cancer model.

Method

MCLs were injected into the mammary cancer and then subjected to an AMF.

Results

Four rats in 20 developed mammary tumors at more than 1 site in the body. The first-developed tumor in each of these 4 rats was selected and heated to over 43°C following administration of MCLs by an infusion pump. After a series of 3 hyperthermia treatments, treated tumors in 3 of the 4 rats were well controlled over a 30-day observation period. One of the 4 rats exhibited regrowth after 2 weeks. In this rat, there were 3 sites of tumor regrowth. Two of these regrowths were reduced in volume and regressed completely after 31 days, although the remaining one grew rapidly. These results indicated hyperthermia-induced immunological antitumor activity mediated by the MCLs.

Conclusion

Our results suggest that hyperthermic treatment using MCLs is effective in a spontaneous cancer model.
The acceptability and feasibility of peer worker support role in community based HCV treatment for injecting drug users
Authors: Norman Josephine , Walsh Nick M , Mugavin Janette , Stoové Mark A , Kelsall Jenny , Austin Kirk , Lintzeris Nick
Published: February 2008

Hepatitis C is the most common blood borne virus in Australia affecting over 200 000 people. Effective treatment for hepatitis C has only become accessible in Australia since the late 1990's, although active injecting drug use (IDU) remained an exclusion criteria for government-funded treatment until 2001. Treatment uptake has been slow, particularly among injecting drug users, the largest affected group. We developed a peer-based integrated model of hepatitis C care at a community drug and alcohol clinic. Clients interested and eligible for hepatitis C treatment had their substance use, mental health and other psychosocial comorbidities co-managed onsite at the clinic prior to and during treatment. In a qualitative preliminary evaluation of the project, nine current patients of the clinic were interviewed, as was the clinic peer worker. A high level of patient acceptability of the peer-based model and an endorsement the integrated model of care was found. This paper describes the acceptability of a peer-based integrated model of hepatitis C care by the clients using the service.
The introduction history of invasive garden ants in Europe: Integrating genetic, chemical and behavioural approaches
Authors: Ugelvig Line V , Drijfhout Falko P , Kronauer Daniel JC , Boomsma Jacobus J , Pedersen Jes S , Cremer Sylvia
Published: February 2008

Background

The invasive garden ant,Lasius neglectus, is the most recently detected pest ant and the first known invasive ant able to become established and thrive in the temperate regions of Eurasia. In this study, we aim to reconstruct the invasion history of this ant in Europe analysing 14 populations with three complementary approaches: genetic microsatellite analysis, chemical analysis of cuticular hydrocarbon profiles and behavioural observations of aggression behaviour. We evaluate the relative informative power of the three methodological approaches and estimate both the number of independent introduction events from a yet unknown native range somewhere in the Black Sea area, and the invasive potential of the existing introduced populations.

Results

Three clusters of genetically similar populations were detected, and all but one population had a similar chemical profile. Aggression between populations could be predicted from their genetic and chemical distance, and two major clusters of non-aggressive groups of populations were found. However, populations ofL. neglectusdid not separate into clear supercolonial associations, as is typical for other invasive ants.

Conclusion

The three methodological approaches gave consistent and complementary results. All joint evidence supports the inference that the 14 introduced populations ofL. neglectusin Europe likely arose from only very few independent introductions from the native range, and that new infestations were typically started through introductions from other invasive populations. This indicates that existing introduced populations have a very high invasive potential when the ants are inadvertently spread by human transport.
Simpson's Paradox, Lord's Paradox, and Suppression Effects are the same phenomenon – the reversal paradox
Authors: Tu Yu-Kang , Gunnell David , Gilthorpe Mark S
Published: February 2008

This article discusses three statistical paradoxes that pervade epidemiological research: Simpson's paradox, Lord's paradox, and suppression. These paradoxes have important implications for the interpretation of evidence from observational studies. This article uses hypothetical scenarios to illustrate how the three paradoxes are different manifestations of one phenomenon – the reversal paradox – depending on whether the outcome and explanatory variables are categorical, continuous or a combination of both; this renders the issues and remedies for any one to be similar for all three. Although the three statistical paradoxes occur in different types of variables, they share the same characteristic: the association between two variables can be reversed, diminished, or enhanced when another variable is statistically controlled for. Understanding the concepts and theory behind these paradoxes provides insights into some controversial or contradictory research findings. These paradoxes show that prior knowledge and underlying causal theory play an important role in the statistical modelling of epidemiological data, where incorrect use of statistical models might produce consistent, replicable, yet erroneous results.
The role of causal reasoning in understanding Simpson's paradox, Lord's paradox, and the suppression effect: covariate selection in the analysis of observational studies
Authors: Arah Onyebuchi A
Published: February 2008

Tu et al present an analysis of the equivalence of three paradoxes, namely, Simpson's, Lord's, and the suppression phenomena. They conclude that all three simply reiterate the occurrence of a change in the association of any two variables when a third variable is statistically controlled for. This is not surprising because reversal or change in magnitude is common in conditional analysis. At the heart of the phenomenon of change in magnitude, with or without reversal of effect estimate, is the question of which to use: the unadjusted (combined table) or adjusted (sub-table) estimate. Hence, Simpson's paradox and related phenomena are a problem of covariate selection and adjustment (when to adjust or not) in the causal analysis of non-experimental data. It cannot be overemphasized that although these paradoxes reveal the perils of using statistical criteria to guide causal analysis, they hold neither the explanations of the phenomenon they depict nor the pointers on how to avoid them. The explanations and solutions lie in causal reasoning which relies on background knowledge, not statistical criteria.
Outcomes and costs of blunt trauma in England and Wales
Authors: Christensen Michael C , Ridley Saxon , Lecky Fiona E , Munro Vicki , Morris Stephen
Published: February 2008

Background

Trauma represents an important public health concern in the United Kingdom, yet the acute costs of blunt trauma injury have not been documented and analysed in detail. Knowledge of the overall costs of trauma care, and the drivers of these costs, is a prerequisite for a cost-conscious approach to improvement in standards of trauma care, including evaluation of the cost-effectiveness of new healthcare technologies.

Methods

Using the Trauma Audit Research Network database, we examined patient records for persons aged 18 years and older hospitalised for blunt trauma between January 2000 and December 2005. Patients were stratified by the Injury Severity Score (ISS).

Results

A total of 35,564 patients were identified; 60% with an ISS of 0 to 9, 17% with an ISS of 10 to 16, 12% with an ISS of 17 to 25, and 11% with an ISS of 26 to 75. The median age was 46 years and 63% of patients were men. Falls were the most common cause of injury (50%), followed by road traffic collisions (33%). Twenty-nine percent of patients were admitted to critical care for a median length of stay of 4 days. The median total hospital length of stay was 9 days, and 69% of patients underwent at least one surgical procedure. Seven percent of the patients died before discharge, with the highest proportion of deaths among those in the ISS 26–75 group (32%). The mean hospital cost per person was £9,530 (± 11,872). Costs varied significantly by Glasgow Coma Score, ISS, age, cause of injury, type of injury, hospital mortality, grade and specialty of doctor seen in the accident and emergency department, and year of admission.

Conclusion

The acute treatment costs of blunt trauma in England and Wales vary significantly by injury severity and survival, and public health initiatives that aim to reduce both the incidence and severity of blunt trauma are likely to produce significant savings in acute trauma care. The largest component of acute hospital cost is determined by the length of stay, and measures designed to reduce length of admissions are likely to be the most effective in reducing the costs of blunt trauma care.
Glycemic penalty index for adequately assessing and comparing different blood glucose control algorithms
Authors: Van Herpe Tom , De Brabanter Jos , Beullens Martine , De Moor Bart , Van den Berghe Greet
Published: February 2008

Introduction

Blood glucose (BG) control performed by intensive care unit (ICU) nurses is becoming standard practice for critically ill patients. New (semi-automated) 'BG control' algorithms (or 'insulin titration' algorithms) are under development, but these require stringent validation before they can replace the currently used algorithms. Existing methods for objectively comparing different insulin titration algorithms show weaknesses. In the current study, a new approach for appropriately assessing the adequacy of different algorithms is proposed.

Methods

Two ICU patient populations (with different baseline characteristics) were studied, both treated with a similar 'nurse-driven' insulin titration algorithm targeting BG levels of 80 to 110 mg/dl. A new method for objectively evaluating BG deviations from normoglycemia was founded on a smooth penalty function. Next, the performance of this new evaluation tool was compared with the current standard assessment methods, on an individual as well as a population basis. Finally, the impact of four selected parameters (the average BG sampling frequency, the duration of algorithm application, the severity of disease, and the type of illness) on the performance of an insulin titration algorithm was determined by multiple regression analysis.

Results

The glycemic penalty index (GPI) was proposed as a tool for assessing the overall glycemic control behavior in ICU patients. The GPI of a patient is the average of all penalties that are individually assigned to each measured BG value based on the optimized smooth penalty function. The computation of this index returns a number between 0 (no penalty) and 100 (the highest penalty). For some patients, the assessment of the BG control behavior using the traditional standard evaluation methods was different from the evaluation with GPI. Two parameters were found to have a significant impact on GPI: the BG sampling frequency and the duration of algorithm application. A higher BG sampling frequency and a longer algorithm application duration resulted in an apparently better performance, as indicated by a lower GPI.

Conclusion

The GPI is an alternative method for evaluating the performance of BG control algorithms. The blood glucose sampling frequency and the duration of algorithm application should be similar when comparing algorithms.
Expression of cell surface receptors and oxidative metabolism modulation in the clinical continuum of sepsis
Authors: Martins Paulo S , Brunialti Milena KC , Martos Leandro SW , Machado Flavia R , Assunçao Murillo S , Blecher Sergio , Salomao Reinaldo
Published: February 2008

Background

Infection control depends on adequate microbe recognition and cell activation, yet inflammatory response may lead to organ dysfunction in sepsis. The aims of this study were to evaluate cell activation in the context of sepsis and its correlation with organ dysfunction.

Methods

A total of 41 patients were prospectively enrolled: 14 with sepsis, 12 with severe sepsis and 15 with septic shock. A total of 17 healthy volunteers were included as a control group. Patients were admitted to the Intensive Care Units and Emergency Rooms of Hospital Sao Paulo (Federal University of Sao Paulo) and Hospital Santa Marcelina, Sao Paulo, Brazil. Toll-like receptor (TLR)2, TLR4, CD11b, CD11c and CD66b expression on neutrophil surfaces and oxidative metabolism measured by non-fluorescent dichlorofluorescein (DCFH) oxidation in neutrophils and monocytes, using whole blood, were evaluated using flow cytometry. Organ dysfunction was measured using the sepsis-associated organ failure assessment (SOFA) score.

Results

TLR2 expression on neutrophils was found to be downregulated in septic shock patients compared to healthy volunteers (p = 0.05). No differences were found in CD11b and CD11c expression. CD66b expression was increased in the patient group compared to the control group (p = 0.01). Neutrophil and monocyte oxidative burst was increased in septic patients compared to the control group at baseline and after stimulation with phorbol myristate acetate (PMA), formyl-methionyl-leucyl-phenylalanine (fMLP), lipopolysaccharide (LPS) and Staphylococcus aureus (p < 0.001 and p < 0.01, respectively, for neutrophils and monocytes in all tested conditions). A strong correlation was observed between neutrophil and monocyte oxidative metabolism. A SOFA score of 7 discriminated patients between survivors and non-survivors (area under the curve for reactive oxygen species (ROS) was 0.78; p = 0.02). ROS generation in patients with sepsis and septic shock with SOFA scores > 7 was higher than in patients with SOFA scores < 7, both in neutrophils and monocytes. However, oxidative burst in patients with sepsis was as high as in septic shock.

Conclusion

Surface receptors expression on neutrophils may be modulated across the continuum of sepsis, and enhanced or decreased expression may be found depending on the receptor considered. ROS generation is upregulated both in neutrophils and monocytes in septic patients, and it is differently modulated depending on the stage of the disease and the stimuli used.
UTILLdb, a Pisum sativum in silicoforward and reverse genetics tool
Authors: Dalmais Marion , Schmidt Julien , Le Signor Christine , Moussy Francoise , Burstin Judith , Savois Vincent , Aubert Gregoire , Brunaud Veronique , de Oliveira Yannick , Guichard Cecile , Thompson Richard , Bendahmane Abdelhafid
Published: February 2008

The systematic characterization of gene functions in species recalcitrant to Agrobacterium-based transformation, like Pisum sativum, remains a challenge. To develop a high throughput forward and reverse genetics tool in pea, we have constructed a reference ethylmethane sulfonate mutant population and developed a database, UTILLdb, that contains phenotypic as well as sequence information on mutant genes. UTILLdb can be searched online for TILLING alleles, through the BLAST tool, or for phenotypic information about mutants by keywords.
Injection of lipopolysaccharide induces the migration of splenic neutrophils to the T cell area of the white pulp: role of CD14 and CXC chemokines
Authors: Kesteman Nicolas , Vansanten Georgette , Pajak Bernard , Goyert Sanna M , Moser Muriel
Published: February 2008

There is increasing evidence that neutrophils are involved in the regulation of adaptive immunity. We therefore tested whether these cells may colocalize with T lymphocytes in lymphoid organs. Our results demonstrate that administration of the microbial product LPS induces the migration of neutrophils in the spleen from the red pulp and the marginal zone to the area of the white pulp where T cells reside. This movement is CD14-dependent, whereas the recruitment of neutrophils in the peritoneal cavity is increased in the absence of CD14. Our data further suggest the involvement of the chemokine MIP-2 and keratinocyte-derived chemokine and their receptor CXCR2. We conclude that neutrophils may interact with naïve T cells upon infection/inflammation and that the migration of neutrophils in the lymphoid organs and in the periphery is regulated differently by a signal transduced by CD14
Human monocytes/macrophages are a target ofNeisseria meningitidis Adhesin A(NadA)
Authors: Franzoso Susanna , Mazzon Cristina , Sztukowska Maryta , Cecchini Paola , Kasic Tihana , Capecchi Barbara , Tavano Regina , Papini Emanuele
Published: February 2008

Specific surface proteins of Neisseria meningitidis have been proposed to stimulate leukocytes during tissue invasion and septic shock. In this study, we demonstrate that the adhesin N. meningitidis Adhesin A (NadA) involved in the colonization of the respiratory epithelium by hypervirulent N. meningitidis B strains also binds to and activates human monocytes/macrophages. Expression of NadA on the surface on Escherichia coli does not increase bacterial-monocyte association, but a NadA-positive strain induced a significantly higher amount of TNF-α and IL-8 compared with the parental NadA-negative strain, suggesting that NadA has an intrinsic stimulatory action on these cells. Consistently, highly pure, soluble NadAΔ351–405, a proposed component of an antimeningococcal vaccine, efficiently stimulates monocytes/macrophages to secrete a selected pattern of cytokines and chemotactic factors characterized by high levels of IL-8, IL-6, MCP-1, and MIP-1α and low levels of the main vasoactive mediators TNF-α and IL-1. NadAΔ351–405 also inhibited monocyte apoptosis and determined its differentiation into a macrophage-like phenotype.
Role of Genetic and Nongenetic Factors for Fluorouracil Treatment-Related Severe Toxicity: A Prospective Clinical Trial by the German 5-FU Toxicity Study Group
Authors: Schwab Matthias , Zanger Ulrich M. , Marx Claudia , Schaeffeler Elke , Klein Kathrin , Dippon Jürgen , Kerb Reinhold , Blievernicht Julia , Fischer Joachim , Hofmann Ute , Bokemeyer Carsten , Eichelbaum Michel
Published: February 2008

Purpose

To assess the predictive value of polymorphisms in dihydropyrimidine dehydrogenase (DPYD ), thymidylate synthase (TYMS ), and methylene tetrahydrofolate reductase (MTHFR ) and of nongenetic factors for severe leukopenia, diarrhea, and mucositis related to fluorouracil (FU) treatment.

Patients and Methods

A multicenter prospective clinical trial included 683 patients with cancer treated with FU monotherapy. Toxicity was documented according to World Health Organization grades. DPYD, TYMS, and MTHFR genotypes were determined, and DPYD was resequenced in patients with severe toxicity.

Results

Grade 3 to 4 toxicity occurred in 16.1% of patients. The sensitivity of DPYD*2A genotyping for overall toxicity was 5.5% (95%CI, 0.02 to 0.11), with a positive predictive value of 0.46 (95% CI, 0.19 to 0.75; P = .01). Inclusion of additional DPYD variants improved prediction only marginally. Analysis according to toxicity type revealed significant association of DPYD with mucositis and leukopenia, whereas TYMS was associated with diarrhea. Genotype, female sex, mode of FU administration, and modulation by folinic acid were identified as independent risk factors by multivariable analysis. A previously unrecognized significant interaction was found between sex and DPYD, which resulted in an odds ratio for toxicity of 41.8 for male patients (95% CI, 9.2 to 190; P < .0001) but only 1.33 (95% CI, 0.34 to 5.2) in female patients. Homozygosity for the TYMS enhancer region double repeat allele increased risk for toxicity 1.6-fold (95% CI, 1.08 to 2.22; P = .02).

Conclusion

DPYD, TYMS, and MTHFR play a limited role for FU related toxicity but a pronounced DPYD gene/sex-interaction increases prediction rate for male patients. Toxicity risk assessment should include sex, mode of administration, and folinic acid as additional predictive factors.
The Siamese Twins in Late-Nineteenth-Century Narratives of Conflict and Reconciliation
Authors: Wu Cynthia
Published: February 2008

This essay uses both ethnic studies and disability studies to read two late-nineteenth-century American texts that refer to Chang and Eng Bunker, conjoined twin entertainers from the country then known as Siam who were popularly called the Siamese Twins. Mark Twain's sketch “Personal Habits of the Siamese Twins” and Thomas Nast's political cartoon “The American Twins” use Chang and Eng Bunker as metaphors to discuss national unity at key moments when that unity appears to be most pressing. While these patriotic visions of unity appear to be inclusive, they are ultimately race-, gender-, and class-specific—implying that they apply only to white, class-privileged men. Moreover, Chang and Eng's status as Asian-raced and anatomically anomalous figures functions strategically in the rhetoric of both Twain and Nast. The twins are alternately rendered racially exotic and domesticated for the Anglo-American reading public. Their conjoinment similarly functions in ambivalent ways that both celebrate unity and suggest discomfort with it.
Hybridity, Identity, and Representation in La Mollie and the King of Tears
Authors: Obourn Megan
Published: February 2008

Through a reading of Arturo Islas's posthumously published La Mollie and the King of Tears, this essay offers a critique of liberal, multicultural uses of postcolonial hybridity in the context of U.S. literature and literary criticism. The essay reviews current uses of hybridity as a celebratory model of either an ideal embodied pluralism or a free-floating deconstructive signifier. It presents an alternative model in Islas's use of hybridity for critiquing readerly desires for identity representation and common, everyday habits of thinking of identity in terms of a one-to-one relation between an identity category and an individual body. In La Mollie, sexuality, ethnicity, and race are revealed to be always mutually constituted. They become legible simultaneously as inhabited positions, projected identifications, and metaphors used to describe both internal and external spaces too complicated to house individual and whole identities. Through such representations of sexuality, ethnicity, and race, Islas presents hybridity as both a (sometimes violently) lived experience and a conscious literary aesthetic. The essay ends by discussing how Islas places his readers in a psychic space where they must recognize the historical circumstances that have produced inequality through identity and desire, and their own complicity in this production.
The Importance of Initiatory Ordeals: Kinship and Politics in an Inca Narrative
Authors: Yaya Isabel
Published: February 2008

Among all the Inca sovereigns whose memory had been preserved by the Spanish chroniclers, Yahuar Huacac holds a unique position. He is famed for having shed tears of blood as a child when a foreign lord kidnapped and maltreated him. Surprisingly, his sufferings ended with matrimonial alliances binding the Inca and the main actors of this drama, all important figures of three foreign chiefdoms. Through both a historical and an anthropological approach, this article analyzes the narrative's structure of interwoven ritual events and kinship patterns. It examines how the stages of the heir's journey over many territories forged a distinctive relationship between the Inca elite and the provincial lords, enlightening the meaning of the final unions.
Getting a peace of the action: measures of post traumatic stress in UK military peacekeepers
Authors: Greenberg Neil , Iversen Amy , Hull Lisa , Bland Duncan , Wessely Simon
Published: February 2008

Objectives This study aimed to measure prevalence of post traumatic stress disorder (PTSD) in a sample of UK Armed Forces peacekeepers. The study also aimed to explore the influence of deploying without an established peer group (deployment status) upon health outcomes using an accepted diagnostic tool for PTSD (PCL-M) and an alternative measure of post-traumatic distress.

Design Using a sub-sample of the King's military cohort we surveyed personnel that deployed on peacekeeping operations between 1991 and 2000 ( n=1198).

Setting Respondents' mean age was 36 years (min, 23 to max, 60) and 81% ( n=964) were serving in the Armed Forces at the time of participation.

Main outcome measures PTSD prevalence was determined in British military peacekeepers using the PLC-M (cut-offs 44 and 50), the General Health Questionnaire (GHQ-12) and a composite brief measure of potential post traumatic symptomology, ‘PostTraumatic Stress Reaction’ (PTSR) for comparison.

Results PTSD prevalence varied from 3.6 to 5.5%. Officers and married personnel were less likely to be cases. Neither gender, age or deployment status influenced PTSD prevalence.

Conclusions PTSD was an uncommon disorder in this sample of British military peacekeepers, with prevalence rates being lower than those reported by other nations. Deploying without an established peer group was not associated with developing PTSD. We postulate that differences in culture and operational practices may account for the lower rates of PTSD.
A lady with unresolved loin pain
Authors: Chow Kai Ming , Lee Kirsty Wai Chung , Wong Tiffany Cho Lam , Szeto Cheuk Chun
Published: February 2008

A history of cardiac disease, especially atrial fibrillation, together with symptoms such as loin or abdominal pain, and accompanied by an elevated lactate dehydrogenase should prompt a computed tomography scan to exclude the diagnosis of acute renal infarction.
Efficient Jump Ahead for 𝔽2-Linear Random Number Generators
Authors: Haramoto Hiroshi , Matsumoto Makoto , Nishimura Takuji , Panneton François , L'Ecuyer Pierre
Published: February 2008

The fastest long-period random number generators currently available are based on linear recurrences modulo 2. So far, software that provides multiple disjoint streams and substreams has not been available for these generators because of the lack of efficient jump-ahead facilities. In principle, it suffices to multiply the state (a k-bit vector) by an appropriate k × k binary matrix to find the new state far ahead in the sequence. However, when k is large (e.g., for a generator such as the popular Mersenne twister, for which k = 19,937), this matrix-vector multiplication is slow, and a large amount of memory is required to store the k × k matrix. In this paper, we provide a faster algorithm to jump ahead by a large number of steps in a linear recurrence modulo 2. The method uses much less than the k2 bits of memory required by the matrix method. It is based on polynomial calculus modulo the characteristic polynomial of the recurrence, and uses a sliding window algorithm for the multiplication.
The Behavioural Analysis Interview: Clarifying the Practice, Theory and Understanding of its Use and Effectiveness
Authors: Horvath Frank , Blair J. P. , Buckley Joseph P.
Published: February 2008

The Behavioural Analysis Interview (BAI) is the only questioning method that has been developed specifically to help investigators sort those who are likely to be ‘guilty’ from those who are not. In its typical application the BAI is a pre-interrogation interview that is used to focus interrogational effort; however, it also can be used independently in order to circumscribe investigative efforts in those cases in which there is a fixed and relatively large number of ‘suspects’. In this paper an overview of the BAI process is provided and the findings and limitations of the extant bodies of field and laboratory research on the BAI are discussed. The paper concludes with suggestions to guide future research on the BAI.
Reasons for Choosing a Police Career: Changes over Two Decades
Authors: Foley Pamela F. , Guarneri Cristina , Kelly Mary E.
Published: February 2008

In recent years, police officers in the US have been under increased public scrutiny, which may have affected both the public perception of the police as well as the desire of individuals to choose a career in law enforcement. In particular, many police departments have been criticised for their treatment of racial and ethnic minorities. This study compared responses of 131 police recruits and graduates with the results of a study with an earlier cohort of this population conducted in 1983. The goals of the present study were (a) to determine whether the relative importance of reported reasons for choosing a police career had changed; (b) to evaluate how demographic variables may play a role in career choice; and (c) to replicate the factor structure of the original questionnaire to assess its ongoing utility. Results indicated that the relative importance of reasons changed slightly, with small but significant differences for women and minorities. The factor structure of the original study was essentially replicated, indicating that the factors motivating individuals to seek a police career have remained stable over time. These results are discussed in terms of their implications for career counsellors working with individuals considering a career in police work.
Sexual Assault Crisis Centre Workers' Perceptions of Law Enforcement: Defining the Situation from a Systems Perspective
Authors: Payne Brian K. , Thompson R. Alan
Published: February 2008

To date, the literature tends to be rife with research examining individuals' perceptions of the police. Most of this research had focused on how members of the public perceived law enforcement. Missing from this research were two types of studies: (1) those examining how certain types of professionals perceive the problems they have collaborating with law enforcement; and (2) those examining the consequences of those perceptions. This study addressed that void by considering how 44 sexual assault crisis workers described their experiences in collaborating with law enforcement agencies. In the discussion, attention was given to the possible consequences of these perceptions. Implications are provided.
A Comparison of Occupational Attitudes between Taiwanese and American Police Officers
Authors: Sun Ivan Y. , Chu Doris C.
Published: February 2008

This study examines attitudinal differences between Taiwanese and American police officers. Data used in this research were collected from two Taiwanese cities, Taipei and Kaohsiung, and two American cities, Indianapolis and St Petersburg. Occupational attitudes are assessed along four dimensions: order maintenance, community building, selective enforcement and distrust of citizens. The results indicate that, compared with their American counterparts, Taiwanese officers are more likely to support community building and distrust of citizens and less likely to favour selective enforcement. Taiwanese and American officers, however, do not differ much in their attitudes toward order maintenance. Implications for future research and policy are discussed.
Unpacking Public Attitudes to the Police: Contrasting Perceptions of Misconduct with Traditional Measures of Satisfaction
Authors: Miller Joel , Davis Robert C
Published: February 2008

Much research on public attitudes to the police in the United States has focused on perceptions of police effectiveness and responsiveness rather than police misconduct. This research has also tended to rely primarily on experiences of direct personal contacts with police and, more recently, neighbourhood to explain demographic differences in public opinion. This article uses data from a five-neighbourhood community survey to extend this focus. It tests four hypotheses: (1) public attitudes about police misconduct are distinct from their attitudes about police effectiveness and responsiveness; (2) determinants of attitudes about police misconduct are different from those relating to police effectiveness and responsiveness; (3) negative experiences of police among friends, family and associates impact on personal attitudes to the police; (4) attitudes toward the police are affected by the character of news coverage to which members of the public are exposed. Using principal components analysis and ANCOVA models, the research finds support for all four hypotheses. The research underscores how perceptions of police misconduct are more sensitive to media influences, race and neighbourhood factors and police-initiated contacts, than traditional measures of public confidence.