Parasite-encoded variant surface antigens (VSAs) like the var gene–encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family are responsible for antigenic variation and infected red blood cell (RBC) cytoadhesion in P. falciparum malaria. Parasites causing severe malaria in nonimmune patients tend to express a restricted subset of VSA (VSASM) that differs from VSA associated with uncomplicated malaria and asymptomatic infection (VSAUM). We compared var gene transcription in unselected P. falciparum clone 3D7 expressing VSAUM to in vitro–selected sublines expressing VSASM to identify PfEMP1 responsible for the VSASM phenotype. Expression of VSASM was accompanied by up-regulation of Group A var genes. The most prominently up-regulated Group A gene (PFD1235w/MAL7P1.1) was translated into a protein expressed on the infected RBC surface. The proteins encoded by Group A var genes, such as PFD1235w/MAL7P1.1, appear to be involved in the pathogenesis of severe disease and are thus attractive candidates for a vaccine against life-threatening P. falciparum malaria.

MDMA (3,4-methylenedioxymethamphetamine or "ecstasy") is a recreationally used drug with remarkable and characteristic prosocial effects. In spite of abundant attention in the scientific literature, the mechanism of its prosocial effects has not been elucidated in humans. Recently, research in animals has suggested that the neuropeptide oxytocin may induce these effects. In a double blind, randomized, crossover, and placebo-controlled study in 15 healthy volunteers we assessed blood oxytocin and MDMA concentrations and subjective prosocial effects after oral administration of 100 mg MDMA or placebo. MDMA induced a robust increase of blood oxytocin concentrations and an increase of subjective prosocial feelings. Within subjects, the variations in these feelings were significantly and positively correlated with variation in oxytocin levels, and the correlations between these feelings and oxytocin were significantly stronger than those between these feelings and blood MDMA levels. MDMA induces oxytocin release in humans, which may be involved in the characteristic prosocial effects of ecstasy.

Determination of the number of malaria parasites by routine or even expert microscopy is not always sufficiently sensitive for detailed quantitative studies on the population dynamics of Plasmodium falciparum, such as intervention or vaccine trials. To circumvent this problem, two more sensitive assays, real-time quantitative nucleic acid sequence-based amplification (QT-NASBA) and real-time quantitative PCR (QT-PCR) were compared for quantification of P. falciparum parasites. QT-NASBA was adapted to molecular beacon real-time detection technology, which enables a reduction of the time of analysis and of contamination risk while retaining the specificity and sensitivity of the original assay. Both QT-NASBA and QT-PCR have a sensitivity of 20 parasites/ml of blood, but QT-PCR requires a complicated DNA extraction procedure and the use of 500 l of venous blood to achieve this sensitivity, compared to 50 l of finger prick blood for real-time QT-NASBA. Both techniques show a significant correlation to microscopic parasite counts, and the quantification results of the two real-time assays are significantly correlated for in vitro as well as in vivo samples. However, in comparison to real-time QT-PCR, the results of real-time QT-NASBA can be obtained 12 h earlier, with relatively easy RNA extraction and use of finger prick blood samples. The prospective development of multiplex QT-NASBA for detection of various P. falciparum developmental stages increases the value of QT-NASBA for malaria studies. Therefore, for studies requiring sensitive and accurate detection of P. falciparum parasites in large numbers of samples, the use of real-time QT-NASBA is preferred over that of real-time QT-PCR.Routine clinical diagnosis of malaria is usually based on microscopic detection of Plasmodium parasites in blood smears. However, this technique is relatively laborious when large numbers of samples need to be quantified simultaneously. Furthermore, the detection limit of microscopy, 1 to 20 parasites per l of blood, may not always be sufficiently sensitive. Parasite densities below the detection level of microscopy may play an important role in Plasmodium population dynamics and the epidemiology of the disease; therefore, the availability and use of more-sensitive detection techniques is a prerequisite for many research projects. With the rapid developments in the field of molecular biology, several nucleic acid-based amplification methods, including PCR, reverse transcriptase PCR, and nucleic acid sequence-based amplification (NASBA) (2, 3, 7-9, 11), are now available for detection of Plasmodium parasites. Because many studies require accurate and sensitive quantification of parasites, most of these techniques have been adapted for quantitative analysis (1,3,6,7,11). In preparation for vaccine trials and epidemiological studies directed at evaluation of interventions, the present study was designed to evaluate the newly developed real-time quantitative NASBA (QT-NASBA) and to compare the assay to another quantitative nucleic acidba...

The aim of this prospective study was to evaluate the value of 18 F-FDG PET for the assessment of chemotherapy response in patients with non-small cell lung cancer. Furthermore, part of the objective of this study was to compare 2 methods to quantify changes in glucose metabolism. Methods: In 51 patients, dynamic 18 F-FDG PET was performed before and at 5-8 wk into treatment. Simplified methods to measure glucose metabolism (standardized uptake value [SUV]) and quantitative measures (metabolic rate of glucose [MR Glu ]), derived from Patlak analysis, were evaluated. The overall survival and progression-free survival with respect to MR Glu and SUV were calculated using Kaplan-Meier estimates. Fractional changes in tumor glucose use were stratified by the median value and also the predefined EORTC (European Organization for Research and Treatment of Cancer) metabolic response criteria, and criteria applying cutoff levels similar to those of RECIST (Response Evaluation Criteria in Solid Tumors) were evaluated. Results: When stratifying at the median value of DMR Glu and DSUV, the difference in overall survival (P 5 0.017 for DMR Glu , P 5 0.018 for DSUV) and progressionfree survival (P 5 0.002 for DMR Glu , P 5 0.0009 for DSUV) was highly significant. When applying the predefined criteria for metabolic response, the cutoff levels as also used for size measurement (RECIST) showed significant differences for DSUV between response categories in progression-free survival (P 5 0.0003) as well as overall survival (P 5 0.027). Conclusion: The degree of chemotherapy-induced changes in tumor glucose metabolism as determined by 18 F-FDG PET is highly predictive for patient outcome, stratifying patients into groups with widely differing overall survival and progression-free survival probabilities. The use of 18 F-FDG PET for therapy monitoring seems clinically feasible, because simplified methods to measure tumor glucose use (SUV) are sufficiently reliable and can replace more complex, quantitative measures (MR Glu ) in this patient population.

Background Plasmodium falciparum Apical Membrane Antigen 1 (PfAMA1) is a candidate vaccine antigen expressed by merozoites and sporozoites. It plays a key role in red blood cell and hepatocyte invasion that can be blocked by antibodies.Methodology/Principal FindingsWe assessed the safety and immunogenicity of recombinant PfAMA1 in a dose-escalating, phase Ia trial. PfAMA1 FVO strain, produced in Pichia pastoris, was reconstituted at 10 µg and 50 µg doses with three different adjuvants, Alhydrogel™, Montanide ISA720 and AS02 Adjuvant System. Six randomised groups of healthy male volunteers, 8–10 volunteers each, were scheduled to receive three immunisations at 4-week intervals. Safety and immunogenicity data were collected over one year. Transient pain was the predominant injection site reaction (80–100%). Induration occurred in the Montanide 50 µg group, resulting in a sterile abscess in two volunteers. Systemic adverse events occurred mainly in the AS02 groups lasting for 1–2 days. Erythema was observed in 22% of Montanide and 59% of AS02 group volunteers. After the second dose, six volunteers in the AS02 group and one in the Montanide group who reported grade 3 erythema (>50 mm) were withdrawn as they met the stopping criteria. All adverse events resolved. There were no vaccine-related serious adverse events. Humoral responses were highest in the AS02 groups. Antibodies showed activity in an in vitro growth inhibition assay up to 80%. Upon stimulation with the vaccine, peripheral mononuclear cells from all groups proliferated and secreted IFNγ and IL-5 cytokines.Conclusions/SignificanceAll formulations showed distinct reactogenicity profiles. All formulations with PfAMA1 were immunogenic and induced functional antibodies.Trial RegistrationClinicaltrials.gov NCT00730782