The glutathione biosynthetic pathway of Plasmodium is essential for mosquito transmission

1Infection of red blood cells (RBC) subjects the malaria parasite to oxidative stress. Therefore, efficient antioxidant and redox systems are required to prevent damage by reactive oxygen species. Plasmodium spp. have thioredoxin and glutathione (GSH) systems that are thought to play a major role as antioxidants during blood stage infection. In this report, we analyzed a critical component of the GSH biosynthesis pathway using reverse genetics. Plasmodium berghei parasites lacking expression of gamma-glutamylcysteine synthetase (γ-GCS), the rate limiting enzyme in de novo synthesis of GSH, were generated through targeted gene disruption thus demonstrating, quite unexpectedly, that γ-GCS is not essential for blood stage development. Despite a significant reduction in GSH levels, blood stage forms of pbggcs− parasites showed only a defect in growth as compared to wild type. In contrast, a dramatic effect on development of the parasites in the mosquito was observed. Infection of mosquitoes with pbggcs− parasites resulted in reduced numbers of stunted oocysts that did not produce sporozoites. These results have important implications for the design of drugs aiming at interfering with the GSH redox-system in blood stages and demonstrate that de novo synthesis of GSH is pivotal for development of Plasmodium in the mosquito

Vacationers Happier, but Most not Happier After a Holiday

The aim of this study was to obtain a greater insight into the association between vacations and happiness. We examined whether vacationers differ in happiness, compared to those not going on holiday, and if a holiday trip boosts post-trip happiness. These questions were addressed in a pre-test/post-test design study among 1,530 Dutch individuals. 974 vacationers answered questions about their happiness before and after a holiday trip. Vacationers reported a higher degree of pre-trip happiness, compared to non-vacationers, possibly because they are anticipating their holiday. Only a very relaxed holiday trip boosts vacationers’ happiness further after return. Generally, there is no difference between vacationers’ and non-vacationers’ post-trip happiness. The findings are explained in the light of set-point theory, need theory and comparison theory

Early chronic kidney disease: diagnosis, management and models of care

Chronic kidney disease (CKD) is prevalent in many countries, and the costs associated with the care of patients with end-stage renal disease (ESRD) are estimated to exceed US$1 trillion globally. The clinical and economic rationale for the design of timely and appropriate health system responses to limit the progression of CKD to ESRD is clear. Clinical care might improve if early-stage CKD with risk of progression to ESRD is differentiated from early-stage CKD that is unlikely to advance. The diagnostic tests that are currently used for CKD exhibit key limitations; therefore, additional research is required to increase awareness of the risk factors for CKD progression. Systems modelling can be used to evaluate the impact of different care models on CKD outcomes and costs. The US Indian Health Service has demonstrated that an integrated, system-wide approach can produce notable benefits on cardiovascular and renal health outcomes. Economic and clinical improvements might, therefore, be possible if CKD is reconceptualized as a part of primary care. This Review discusses which early CKD interventions are appropriate, the optimum time to provide clinical care, and the most suitable model of care to adopt

Do positive or negative experiences of social support relate to current and future health? Results from the Doetinchem Cohort Study

Cross-sectional studies have reported associations between social support and health, but prospective evidence is less conclusive. This study aims to investigate the associations of positive and negative experiences of social support with current and future lifestyle factors, biological risk factors, self-perceived health and mental health over a 10-year period

Vaginographic examination of the pelvic floor

In women with genital prolapse, damage to the pelvic floor muscles, fasciae, and ligaments leads to characteristic changes in the shape and position of the vagina. This observational study was undertaken to determine how these changes can be used to document damage to individual pelvic floor structures. Resting and straining radiographs in the standing position with barium in the vagina were made of 23 women with normal and 31 women with abnormal support, and correlated with anatomic studies of 23 cadavers. These studies demonstrate that the downward sagging of the upper vagina seen in frontal radiographs reflects a failure of the cardinal-uterosacral complex. Loss of the lateral indentations in the lower vagina indicates loss of the constricting effects of the levator ani. In lateral radiographs the levator plate's inclination can be measured. The distance between the pubic symphysis and anterior perineal body indicates the levator ani muscles' closure of the vagina. A line from the lower pubic symphysis to the ischial spine represents the location of the arcus tendineus fasciae pelvis. The distance between this line and the anterior vaginal wall indicates the status of the pubocervical fascia and its attachment to the arcus. With these observations, the vaginogram can be used to examine the status of the fascial and muscular supports of the vagina. It offers a research tool for the study of individual parts of the supportive system, and can be applied to such questions as the frequency of damage to muscles, fasciae or ligaments in recurrent prolapse.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45901/1/192_2004_Article_BF00451707.pd