Simple In Vitro Assay for Determining the Sensitivity of Plasmodium vivax Isolates from Fresh Human Blood to Antimalarials in Areas where P. vivax Is Endemic

The aim of this study was to develop a simple, field-practical, and effective in vitro method for determining the sensitivity of fresh erythrocytic Plasmodium vivax isolates to a range of antimalarials. The method used is a modification of the standard World Health Organization (WHO) microtest for determination of P.falciparum drug sensitivity. The WHO method was modified by removing leukocytes and using a growth medium supplemented with AB(+) serum. We successfully carried out 34 in vitro drug assays on 39 P. vivax isolates collected from the Mae Sod malaria clinic, Tak Province, Thailand. The mean percentage of parasites maturing to schizonts (six or more merozoites) in control wells was 66.5% +/- 5.9% (standard deviation). This level of growth in the control wells enabled rapid microscopic determination (5 min per isolate per drug) of the MICs of chloroquine, dihydroartemisinin, WR238605 (tafenoquine), and sulfadoxine. P. vivax was relatively sensitive to chloroquine (MIC = 160 ng/ml, 50% inhibitory concentration [IC50] = 49.8 ng/ml) and dihydroartemisinin (MIC = 0.5 ng/ml, IC50 = 0.47 ng/ml). The poor response of P. vivax to both tafenoquine (MIC = 14,000 ng/ml, IC50 = 9,739 ng/ml) and sulfadoxine (MIC = 500,000 ng/ml, IC50 = 249,000 ng/ml) was due to the slow action of these drugs and the innate resistance of P. vivax to sulfadoxine. The in vitro assay developed in our study should be useful both for assessing the antimalarial sensitivity of P. vivax populations and for screening new antimalarials in the absence of long-term P. vivax cultures.

Identification of the semaphorin receptor PLXNA2 as a candidate for susceptibility to schizophrenia

The discovery of genetic factors that contribute to schizophrenia susceptibility is a key challenge in understanding the etiology of this disease. Here, we report the identification of a novel schizophrenia candidate gene on chromosome 1q32, plexin A2 (PLXNA2), in a genome-wide association study using 320 patients with schizophrenia of European descent and 325 matched controls. Over 25 000 single-nucleotide polymorphisms (SNPs) located within approximately 14 000 genes were tested. Out of 62 markers found to be associated with disease status, the most consistent finding was observed for a candidate locus on chromosome 1q32. The marker SNP rs752016 showed suggestive association with schizophrenia (odds ratio (OR) = 1.49, P = 0.006). This result was confirmed in an independent case control sample of European Americans (combined OR = 1.38, P = 0.035) and similar genetic effects were observed in smaller subsets of Latin Americans (OR = 1.26) and Asian Americans (OR = 1.37). Supporting evidence was also obtained from two family-based collections, one of which reached statistical significance (OR = 2.2, P = 0.02). High-density SNP mapping showed that the region of association spans approximately 60 kb of the PLXNA2 gene. Eight out of 14 SNPs genotyped showed statistically significant differences between cases and controls. These results are in accordance with previous genetic findings that identified chromosome 1q32 as a candidate region for schizophrenia. PLXNA2 is a member of the transmembrane semaphorin receptor family that is involved in axonal guidance during development and may modulate neuronal plasticity and regeneration. The PLXNA2 ligand semaphorin 3A has been shown to be upregulated in the cerebellum of individuals with schizophrenia. These observations, together with the genetic results, make PLXNA2 a likely candidate for the 1q32 schizophrenia susceptibility locus.

Can we get General Practitioners to Promote Physical Activity? Results of the 10,000 Steps Rockhampton Community-Based Physical Activity Promotion Project

Evidence supporting the efficacy of physical activity promotion in primary care settings has evaluated patient-level changes in physical activity, with little focus on the issue of general practitioner (GP) uptake. The 'GP Strategy' of 10,000 Steps Rockhampton provided an opportunity to explore this issue in the context of a multi-strategy, community-based physical activity intervention project. The 'GP Strategy' was developed in partnership with the Capricornia Division of General Practice. It aimed to: 1) increase GP awareness of the 10,000 Steps project, 2) upskill GPs in brief physical activity counselling techniques, and 3) provide GPs with evidencebased physical activity counselling materials and pedometers. The evaluation, which was guided by the RE-AIM evaluation framework, used a pre-post design, including a GP mailed survey, and collection of process data. Survey response rates were 67% (n=44/66; baseline) and 70% (n=37/53; 14-month follow-up). GP awareness of 10,000 Steps Rockhampton increased from 46% to 97%. 21/23 practices were visited by 10,000 Steps staff and accepted 10,000 Steps posters, brochures, and pedometers. At follow-up, 78% had displayed the poster, 81% were using the brochures, and 70% had loaned pedometers to patients. Despite the very high rate of uptake and use of 10,000 Steps materials, there was no change in the percentage of patients counselled, and relatively few pedometers had been loaned to patients. The results of this trial indicate that it will take more effort to change GP physical activity counselling behaviour, and provide only modest support for use of pedometers in the busy general practice setting. Acknowledgement:This project is supported by a grant from Health Promotion Queensland.