Stage-specific activity of potential antimalarial compounds measured in vitro by flow cytometry in comparison to optical microscopy and hypoxanthine uptake

The evaluation of new antimalarial agents using older methods of monitoring sensitivity to antimalarial drugs are laborious and poorly suited to discriminate stage-specific activity. We used flow cytometry to study the effect of established antimalarial compounds, cysteine protease inhibitors, and a quinolone against asexual stages of Plasmodium falciparum. Cultured P. falciparum parasites were treated for 48 h with different drug concentrations and the parasitemia was determined by flow cytometry methods after DNA staining with propidium iodide. P. falciparum erythrocytic life cycle stages were readily distinguished by flow cytometry. Activities of established and new antimalarial compounds measured by flow cytometry were equivalent to results obtained with microscopy and metabolite uptake assays. The antimalarial activity of all compounds was higher against P. falciparum trophozoite stages. Advantages of flow cytometry analysis over traditional assays included higher throughput for data collection, insight into the stage-specificity of antimalarial activity avoiding use of radioactive isotopes.

Live 4 LIFE (Lifestyle Intervention for Food and Exercise)

Primary aims of this intervention are weight management and behaviour change of children 7-16 years old and secondary aims include parental weight management and increase in self esteem and confidence in both children and their families. The Referred Child:Will understand the importance of healthy eating and physical activity.Be able to make informed choices.Will have increased confidence and self esteem. The Parents:Will understand the importance of healthy eating and physical activity.Be able to make informed choices for themselves and their children.Feel empowered to continue a healthy lifestyle. The Family:Will understand the importance of healthy eating and physical activity.Will be able to work as a team to encourage each other to make healthy choices.Will feel confident enough to continue activities together.

Fecundity of ant queens in relation to their age and the mode of colony founding

The change over time in the fecundity and weight of queens was investigated in three monogynous, independent colony founding species,Lasius niger, Camponotus ligniperda andC. herculaneus, and two polygynous dependent colony founding species,Plagiolepis pygmaea andIridomyrmex humilis. Queens of the three species founding independently exhibited a similar pattern with a significant loss of weight between mating and the emergence of the first workers. In contrast, weights of queens of the species employing dependent colony founding remained more stable. Fecundity of queens founding independently increased slowly with time whereas fecundity of queens founding dependently reached the maximum level some weeks after the beginning of the first reproductive season. These results are discussed in relation to some differences in the life history (e.g., life-span) between queens utilizing independent and dependent colony founding.

Toxoplasma gondii: 1908-2008, homage to Nicolle, Manceaux and Splendore

The discovery of Toxoplasma gondii independently by Nicolle and Manceaux (1908) and Splendore (1908) was to open a "Pandora's Box" that has led research on this parasite into a number of scientific disciplines. In the 100 years since its discovery, the mystery surrounding T. gondii and its inter-relationship with humans has continued to provide a stimulating source of material in many areas of research, resulting in the publication of almost 20,000 papers and a number of books. This flood of diverse information shows no sign of abating, with an average of 10 papers per week appearing in PubMed. Herein, it is impossible to do more than provide a very superficial comment on what has become a massive body of scientific information. T. gondii has many unique features and seems to be the "exception to almost every rule" thus acting as a focus for research in disciplines from epidemiology to immunology to human behaviour to cell biology to human disease. In this review a number of the historical advances will be mentioned and combined with a description of the basic biology of the parasite.

Immune response to Leishmania (Leishmania) chagasi infection is reduced in malnourished BALB/c mice

Protein-energy malnutrition and micronutrient deficiencies may down-regulate immune response and increase morbidity and mortality due to infection. In this study, a murine model was used to study the effects of protein, iron and zinc deficiencies on the immune response to Leishmania (Leishmania) chagasi infection. Mice were initially fed a standard diet or with a diet containing 3% casein but deficient in zinc and iron. After malnutrition was established, mice were inoculated with L. chagasiand sacrificed four weeks later in order to evaluate liver and spleen parasite loads and serum biochemical parameters. Significant decreases in liver and spleen weight, an increase in the parasite loads in these organs and decreases in serum protein and glucose concentrations in malnourished animals were observed. Furthermore, the production of interferon-gamma by spleen cells from infected malnourished mice stimulated by Leishmaniaantigen was significantly lower compared with that in control diet mice. These data suggest that malnutrition alters the immune response to L. chagasiinfection in the BALB/c model and, in association with the effects on biochemical and anatomical parameters of the host, favored increases in the parasite loads in the spleens and livers of these animals.

An Open-Label, Noncomparative, Multicenter Study to Evaluate Efficacy and Safety of NASHA/Dx Gel as a Bulking Agent for the Treatment of Fecal Incontinence

Fecal incontinence (FI) is the involuntary loss of rectal contents through the anal canal. Reports of its prevalence vary from 1-21%. Studies, have demonstrated a positive effect on FI symptoms with injectable bulking agents. This study evaluated the safety and efficacy of NASHA/Dx gel in the treatment of FI. One hundred fifteen eligible patients suffering from FI received 4 injections of 1 mL NASHA/Dx gel. Primary efficacy was based on data from 86 patients that completed the study. This study demonstrated a ≥50% reduction from baseline in the number of FI episodes in 57.1% of patients at 6 months, and 64.0% at 12 months. Significant improvements (P < .001) were also noted in total number of both solid and loose FI episodes, FI free days, CCFIS, and FIQL scores in all 4 domains. The majority of the treatment related AEs (94.9%) were mild or moderate intensity, and (98.7%) of AEs resolved spontaneously, or following treatment, without sequelae. Results of this study indicate NASHA/Dx gel was efficacious in the treatment of FI. Treatment effect was significant both in reduction of number of FI episodes and disease specific quality of life at 6 months and lasted up to 12 months after treatment.

Obesity and survival in operable breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathological subtypes: a pooled analysis.

INTRODUCTION Obesity is an unfavorable prognostic factor in breast cancer (BC) patients regardless of menopausal status and treatment received. However, the association between obesity and survival outcome by pathological subtype requires further clarification. METHODS We performed a retrospective analysis including 5,683 operable BC patients enrolled in four randomized clinical trials (GEICAM/9906, GEICAM/9805, GEICAM/2003-02, and BCIRG 001) evaluating anthracyclines and taxanes as adjuvant treatments. Our primary aim was to assess the prognostic effect of body mass index (BMI) on disease recurrence, breast cancer mortality (BCM), and overall mortality (OM). A secondary aim was to detect differences of such prognostic effects by subtype. RESULTS Multivariate survival analyses adjusting for age, tumor size, nodal status, menopausal status, surgery type, histological grade, hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, chemotherapy regimen, and under-treatment showed that obese patients (BMI 30.0 to 34.9) had similar prognoses to that of patients with a BMI < 25 (reference group) in terms of recurrence (Hazard Ratio [HR] = 1.08, 95% Confidence Interval [CI] = 0.90 to 1.30), BCM (HR = 1.02, 0.81 to 1.29), and OM (HR = 0.97, 0.78 to 1.19). Patients with severe obesity (BMI ≥ 35) had a significantly increased risk of recurrence (HR = 1.26, 1.00 to 1.59, P = 0.048), BCM (HR = 1.32, 1.00 to 1.74, P = 0.050), and OM (HR = 1.35, 1.06 to 1.71, P = 0.016) compared to our reference group. The prognostic effect of severe obesity did not vary by subtype. CONCLUSIONS Severely obese patients treated with anthracyclines and taxanes present a worse prognosis regarding recurrence, BCM, and OM than patients with BMI < 25. The magnitude of the harmful effect of BMI on survival-related outcomes was similar across subtypes.

Health at work and risk factors related to ergonomics: some results from the Swiss sample of the 4th European working conditions survey

Introduction The European Foundation for the improvement of living and working conditions conducts a survey every 5 years since 1990. The foundation also offers the possibility to non-EU countries to be included in the survey: in 2005, Switzerland took part for the first time in the fourth edition of this survey. The Institute for Work and Health (IST) has been associated to the Swiss project conducted under the leadership of the SECO and the Fachhochschule Nordwestschweiz. The survey covers different aspects of work like job characteristics and employment conditions, health and safety, work organization, learning and development opportunities, and the balance between working and non-working life (Parent-Thirion, Fernandez Macias, Hurley, & Vermeylen, 2007). More particularly, one question assesses the worker's self-perception of the effects of work on health. We identified (for the Swiss sample) several factors affecting the risk to report health problems caused by work. The Swiss sample includes 1040 respondents. Selection of participants was based on a random multi-stage sampling and was carried out by M.I.S Trend S.A. (Lausanne). Participation rate was 59%. The database was weighted by household size, gender, age, region of domicile, occupational group, and economic sector. Specially trained interviewers carried out the interviews at the respondents home. The survey was carriedout between the 19th of September 2005 and the 30th of November 2005. As detailed in (Graf et al., 2007), 31% of the Swiss respondents identify work as the cause of health problems they experience. Most frequently reported health problems include back pain (18%), stress (17%), muscle pain (13%), and overall fatigue (11%). Ergonomic aspects associated with higher risk of reporting health problems caused by work include frequent awkward postures (odds ratio [OR] 4.7, 95% confidence interval [CI] 3.1 to 5.4), tasks involving lifting heavy loads (OR 2.7, 95% CI 2.0 to 3.6) or lifting people (OR 2.2, 95% CI 1.4 to 3.5), standing or walking (OR 1.4, 95% CI 1.1 to 1.9), as well as repetitive movements (OR 1.7, 95% CI 1.3 to 2.3). These results highlight the need to continue and intensify the prevention of work related health problems in occupations characterized by risk factors related to ergonomics.

Single-dose oral amoxicillin or linezolid for prophylaxis of experimental endocarditis due to vancomycin-susceptible and vancomycin-resistant Enterococcus faecalis.

Endocarditis prophylaxis following genitourinary or gastrointestinal procedures targets Enterococcus faecalis. Prophylaxis recommendations advocate oral amoxicillin (2 g in the United States and 3 g in the United Kingdom) in moderate-risk patients and intravenous amoxicillin (2 g) or vancomycin (1 g) plus gentamicin in high-risk patients. While ampicillin-resistant (or amoxicillin-resistant) E. faecalis is still rare, there is a concern that these regimens might fail against vancomycin-resistant and/or aminoglycoside-resistant isolates. The present study tested oral linezolid as an alternative. Rats with catheter-induced aortic vegetations were given prophylaxis simulating human pharmacokinetics of oral amoxicillin (2- to 3-g single dose), oral linezolid (600 mg, single or multiple oral doses every 12 h), or intravenous vancomycin (1-g single dose). Rats were then inoculated with the minimum inoculum infecting 90% of the animals (90% infective dose [ID(90)]) or with 10 times the ID(90) of the vancomycin-susceptible E. faecalis strain JH2-2 or the vancomycin-resistant (VanA phenotype) E. faecalis strain UCN41. Amoxicillin was also tested with two additional vancomycin-susceptible E. faecalis strains, 309 and 1209. Animals were sacrificed 3 days later. All the tested bacteria were susceptible to amoxicillin and gentamicin. Single-dose amoxicillin provided 100% protection against all four isolates at both the ID(90) and 10 times the ID(90). In contrast, linezolid required up to four consecutive doses to provide full protection against the vancomycin-resistant isolate. Vancomycin protected only against the vancomycin-susceptible strain. The high efficacy of single-dose oral amoxicillin suggests that this regimen could be used for prophylaxis in both moderate-risk and high-risk patients without additional aminoglycosides. Linezolid appears to be less reliable, at least against the vancomycin-resistant strain.

Predictable Life-Cycle Shocks, Income Risk and Consumption Inequality

Was the increase in income inequality in the US due to permanent shocks or merely to an increase in the variance of transitory shocks? The implications for consumption and welfare depend crucially on the answer to this question. We use CEX repeated cross-section data on consumption and income to decompose idiosyncratic changes in income into predictable life-cycle changes, transitory and permanent shocks and estimate the contribution of each to total inequality. Our model fits the joint evolution of consumption and income inequality well and delivers two main results. First, we find that permanent changes in income explain all of the increase in inequality in the 1980s and 90s. Second, we reconcile this finding with the fact that consumption inequality did not increase much over this period. Our results support the view that many permanent changes in income are predictable for consumers, even if they look unpredictable to the econometrician, consistent with models of heterogeneous income profiles.

Comparison of [3H]tamsulosin and [3H]prazosin binding to wild-type and constitutively active alpha1B-adrenoceptors.

We have tested the hypothesis that smaller alpha1B-adrenoceptor labeling by [3H]tamsulosin compared to [3H]prazosin is related to differential recognition of agonist low affinity states. Paired saturation binding experiments with [3H]prazosin and [3H]tamsulosin were performed in membrane preparations from rat liver and Rat- fibroblasts stably transfected with wild-type hamster alpha1B-adrenoceptors or a constitutively active mutant thereof. In all three settings [3H]tamsulosin labeled significantly fewer alpha1B-adrenoceptors than [3H]prazosin. In noradrenaline competition binding experiments, the percentage of agonist low affinity sites was smallest for the constitutively active alpha1B-adrenoceptor but the percentage of agonist low affinity sites recognized by [3H]tamsulosin and [3H]prazosin did not differ significantly. We conclude that [3H]tamsulosin labels fewer alpha1B-adrenoceptors than [3H]prazosin but this is not fully explained by a poorer labeling of agonist low affinity sites.

A Single High Dose of Oral Vitamin D3 Is Not Enough to Correct Insufficiency and Deficiency in a Rheumatologic Population

Introduction: Vitamin D plays a major role in bone metabolism and neuromuscular function. Supplementation with vitamin D is effective to reduce the risk of fall and of fracture. However adherence to oral daily vitamin D supplementation is low. Screening and correcting vitamin D insufficiency in a general rheumatologic population could improve both morbidity and quality of life in these patients with chronic painful disorders and at high risk of osteoporosis. After determining the prevalence of vitamin D deficiency in this population, we evaluated if supplementation with a single high dose of oral 25-OH vitamin D3 was sufficient to correct this abnormality. Methods: During one month (November 2009), levels of 25-OH vitamin D were systematically determined in our rheumatology outpatient clinic and classified into three groups: vitamin D deficiency (<10 μg/l), vitamin D insufficiency (10 to 30 μg/l) or normal vitamin D (>30 μg/l). Patients with insufficiency or deficiency received respectively a single high dose of 300000 IU or 600000 IU oral vitamin D3. In addition, all patients with osteoporosis were prescribed daily supplement of calcium (1 g) and vitamin D (800 IU). 25-OH vitamin D levels were reevaluated after 3 months. Results: Vitamin D levels were initially determined in 292 patients (mean age 53, 211 women, 87% Caucasian). 77% had inflammatory rheumatologic disease (IRD), 20% osteoporosis (OP) and 12% degenerative disease (DD). Vitamin D deficiency was present in 20 (6.8%), while 225 (77.1%) had insufficiency. Of the 245 patients with levels <30 μg/l, a new determination of vitamin D level was available in 173 (71%) at 3 months. Conclusion: Vitamin D insufficiency is highly prevalent in our rheumatologic population (84%), and is not adequately corrected by a single high dose of oral vitamin D3 in more than half of the patients with IRD and DD. In patients with OP, despite association of a single high dose with daily oral vitamin D supplementation, 40% of patients are still deficient when reevaluated at 3 months.

Illusory correlation in the remuneration of chief executive officers: It pays to play golf, and well

Illusory correlation refers to the use of information in decisions that is uncorrelated with the relevantcriterion. We document illusory correlation in CEO compensation decisions by demonstrating thatinformation, that is uncorrelated with corporate performance, is related to CEO compensation. We usepublicly available data from the USA for the years 1998, 2000, 2002, and 2004 to examine the relationsbetween golf handicaps of CEOs and corporate performance, on the one hand, and CEO compensationand golf handicaps, on the other hand. Although we find no relation between handicap and corporateperformance, we do find a relation between handicap and CEO compensation. In short, golfers earnmore than non-golfers and pay increases with golfing ability. We relate these findings to the difficultiesof judging compensation for CEOs. To overcome this and possibly other illusory correlations inthese kinds of decisions, we recommend the use of explicit, mechanical decision rules.

Heterogeneous life-cycle profiles, income risk and consumption inequality

Was the increase in income inequality in the US due to permanent shocks or merely to an increase in the variance of transitory shocks? The implications for consumption and welfare depend crucially on the answer to this question. We use CEX repeated cross-section data on consumption and income to decompose idiosyncratic changes in income into predictable life-cycle changes, transitory and permanent shocks and estimate the contribution of each to total inequality. Our model fits the joint evolution of consumption and income inequality well and delivers two main results. First, we find that permanent changes in income explain all of the increase in inequality in the 1980s and 90s. Second, we reconcile this finding with the fact that consumption inequality did not increase much over this period. Our results support the view that many permanent changes in income are predictable for consumers, even if they look unpredictable to the econometrician, consistent withmodels of heterogeneous income profiles.

Is confidence in decisions related to feedback? Evidence-and lack of evidence-from random samples of real-world managerial behavior?

Confidence in decision making is an important dimension of managerialbehavior. However, what is the relation between confidence, on the onehand, and the fact of receiving or expecting to receive feedback ondecisions taken, on the other hand? To explore this and related issuesin the context of everyday decision making, use was made of the ESM(Experience Sampling Method) to sample decisions taken by undergraduatesand business executives. For several days, participants received 4 or 5SMS messages daily (on their mobile telephones) at random moments at whichpoint they completed brief questionnaires about their current decisionmaking activities. Issues considered here include differences between thetypes of decisions faced by the two groups, their structure, feedback(received and expected), and confidence in decisions taken as well as inthe validity of feedback. No relation was found between confidence indecisions and whether participants received or expected to receivefeedback on those decisions. In addition, although participants areclearly aware that feedback can provide both confirming and disconfirming evidence, their ability to specify appropriatefeedback is imperfect. Finally, difficulties experienced inusing the ESM are discussed as are possibilities for further researchusing this methodology.