Atorvastatin prevents <Emphasis Type="Italic">Plasmodium falciparum</Emphasis> cytoadherence and endothelial damage

Background

The adhesion of Plasmodium falciparum parasitized red blood cell (PRBC) to human endothelial cells (EC) induces inflammatory processes, coagulation cascades, oxidative stress and apoptosis. These pathological processes are suspected to be responsible for the blood-brain-barrier and other organs' endothelial dysfunctions observed in fatal cases of malaria. Atorvastatin, a drug that belongs to the lowering cholesterol molecule family of statins, has been shown to ameliorate endothelial functions and is widely used in patients with cardiovascular disorders.

Methods

The effect of this compound on PRBC induced endothelial impairments was assessed using endothelial co-culture models.

Results

Atorvastatin pre-treatment of EC was found to reduce the expression of adhesion molecules and P. falciparum cytoadherence, to protect cells against PRBC-induced apoptosis and to enhance endothelial monolayer integrity during co-incubation with parasites.

Conclusions

These results might suggest a potential interest use of atorvastatin as a protective treatment to interfere with the pathophysiological cascades leading to severe malaria.

     

Cost-effectiveness of early versus standard antiretroviral therapy in HIV-infected adults in Haiti

Background

In a randomized clinical trial of early versus standard antiretroviral therapy (ART) in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm³ in Haiti, early ART decreased mortality by 75%. We assessed the cost-effectiveness of early versus standard ART in this trial.

Methods and Findings

Trial data included use of ART and other medications, laboratory tests, outpatient visits, radiographic studies, procedures, and hospital services. Medication, laboratory, radiograph, labor, and overhead costs were from the study clinic, and hospital and procedure costs were from local providers. We evaluated cost per year of life saved (YLS), including patient and caregiver costs, with a median of 21 months and maximum of 36 months of follow-up, and with costs and life expectancy discounted at 3% per annum. Between 2005 and 2008, 816 participants were enrolled and followed for a median of 21 months. Mean total costs per patient during the trial were US$1,381 for early ART and US$1,033 for standard ART. After excluding research-related laboratory tests without clinical benefit, costs were US$1,158 (early ART) and US$979 (standard ART). Early ART patients had higher mean costs for ART (US$398 versus US$81) but lower costs for non-ART medications, CD4 cell counts, clinically indicated tests, and radiographs (US$275 versus US$384). The cost-effectiveness ratio after a maximum of 3 years for early versus standard ART was US$3,975/YLS (95% CI US$2,129/YLS–US$9,979/YLS) including research-related tests, and US$2,050/YLS excluding research-related tests (95% CI US$722/YLS–US$5,537/YLS).

Conclusions

Initiating ART in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm³ in Haiti, consistent with World Health Organization advice, was cost-effective (US$/YLS <3 times gross domestic product per capita) after a maximum of 3 years, after excluding research-related laboratory tests.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00120510","term_id":"NCT00120510"}}NCT00120510 Please see later in the article for the Editors'' Summary     

Alder forests of Numidia (N.E. Algeria): floristic biodiversity, vulnerability and conservation

The phytoecological study of the alder forests of north-east Algeria shows that these habitats with boreal affinities harbour very high species richness (> 400 species) and complex structures, which suggest their ancient origin. They correspond phytosociologically to two syntaxa, the Campanulo alatae-Alnenion glutinosae (riparian alder forests) and the Rusco hypophylli-Alnetum glutinosae (peat-forming alder carrs), respectively. Their degraded state and their regressive dynamics, observed during the 14 years of the study, reveal their precarious situation and their rapid ongoing decline under the influence of human-induced uncontroled disturbances (cutting, burning, draining, dumping…). With regard to their ecological, historical and patrimonial importance, the alder forests of Algerian Numidia should be urgently protected, with the aim of assuring the perennity of their exceptional floristic corteges.     

The genomes of fermentative Saccharomyces

Many different yeast species can take part in spontaneous fermentations, but the species of the genus Saccharomyces, including Saccharomyces cerevisiae in particular, play a leading role in the production of fermented beverages and food. In recent years, the development of whole-genome scanning techniques, such as DNA chip-based analysis and high-throughput sequencing methods, has considerably increased our knowledge of fermentative Saccharomyces genomes, shedding new light on the evolutionary history of domesticated strains and the molecular mechanisms involved in their adaptation to fermentative niches. Genetic exchange frequently occurs between fermentative Saccharomyces and is an important mechanism for generating diversity and for adaptation to specific ecological niches. We review and discuss here recent advances in the genomics of Saccharomyces species and related hybrids involved in major fermentation processes.     

New perspectives in hemiascomycetous yeast taxonomy

DNA sequencing has revolutionized yeast taxonomy. Although initially rDNA sequences proved to be universal and convenient for assigning phylogenetic relationships, it was eventually supplanted by multigene analysis, which provided more discriminating and robust results. This led to a new classification of the major yeast clades, which is still used as a reference today. More recently, the availability of a large number of complete genome sequences has given a new perspective on the molecular taxonomy of yeasts by providing a high number of genes to compare. It also highlighted an unexpected aspect of yeast genome evolution: the existence of interspecific hybrids outside of the industrial Saccharomyces clade. Together with the loss of heterozygosity in interspecific hybrids and a reduced sexuality leading to clonal propagation, this observation obliges us to reexamine the present concept of species. In parallel, the ongoing challenge is to find a universal molecular marker, to improve fast authentication and, if possible, phylogeny of yeasts. The future of yeast taxonomy will involve the sequencing of more genomes, thorough analysis of populations to obtain a good representation of the biodiversity and integration of these data into dedicated databases.     

Contrasting diversity patterns of crenarchaeal, bacterial and fungal soil communities in an alpine landscape

Background

The advent of molecular techniques in microbial ecology has aroused interest in gaining an understanding about the spatial distribution of regional pools of soil microbes and the main drivers responsible of these spatial patterns. Here, we assessed the distribution of crenarcheal, bacterial and fungal communities in an alpine landscape displaying high turnover in plant species over short distances. Our aim is to determine the relative contribution of plant species composition, environmental conditions, and geographic isolation on microbial community distribution.

Methodology/Principal Findings

Eleven types of habitats that best represent the landscape heterogeneity were investigated. Crenarchaeal, bacterial and fungal communities were described by means of Single Strand Conformation Polymorphism. Relationships between microbial beta diversity patterns were examined by using Bray-Curtis dissimilarities and Principal Coordinate Analyses. Distance-based redundancy analyses and variation partitioning were used to estimate the relative contributions of different drivers on microbial beta diversity. Microbial communities tended to be habitat-specific and did not display significant spatial autocorrelation. Microbial beta diversity correlated with soil pH. Fungal beta-diversity was mainly related to soil organic matter. Though the effect of plant species composition was significant for all microbial groups, it was much stronger for Fungi. In contrast, geographic distances did not have any effect on microbial beta diversity.

Conclusions/Significance

Microbial communities exhibit non-random spatial patterns of diversity in alpine landscapes. Crenarcheal, bacterial and fungal community turnover is high and associated with plant species composition through different set of soil variables, but is not caused by geographical isolation.     

McMaster-Toronto Arthritis Patient Preference Disability Questionnaire sensitivity to change in low back pain: influence of shifts in priorities

Objective

To assess the sensitivity to change of the McMaster Toronto Arthritis Patient Preference Disability Questionnaire (MACTAR) in chronic low back pain (CLBP) and shifts in patients'' priorities of disabling activities over time.

Methods

A prospective longitudinal survey of 100 patients (38 males) with CLBP in a tertiary care teaching hospital. Evaluation at baseline and 6 months by the MACTAR, Quebec Back Pain Disability Questionnaire (QUEBEC), Hospital Anxiety and Depression scale (HAD), Fear-Avoidance Beliefs Questionnaire (FABQ), Coping Strategies Questionnaire (CSQ), and pain and handicap visual analogue scales (VASs). Patients'' perceived improvement or worsening of condition was assessed at 6 months. Effect size (ES) and Standardized response mean (SRM) and effect size (ES) were used to evaluate sensitivity to change of the MACTAR.

Results

The MACTAR SRM and ES values (SRM = 0.25; ES = 0.37) were among the highest for the instruments evaluated. For patients considering their condition as improved, the SRM was 0.66 and the ES 1. The 3 disability domains, classified by the International Classification of Functioning, Disability and Health (ICF), most often cited as priorities at baseline remained the most cited at follow-up: mobility (40.9% of patients); community, social and civic life (22.7%); and domestic life (22.4%). At 6 months, 48 patients shifted their priorities, for a decrease in MACTAR SRM and ES values for patients considering their condition improved and an increase in these values for those considering their condition deteriorated.

Conclusions

Although the MACTAR has similar sensitivity to change as other outcome measures widely used in CLBP, shifts in patient priorities over time are common and influence scores and sensitivity to change.     

How Do Tsetse Recognise Their Hosts? The Role of Shape in the Responses of Tsetse (Glossina fuscipes and G. palpalis) to Artificial Hosts

Palpalis-group tsetse, particularly the subspecies of Glossina palpalis and G. fuscipes, are the most important transmitters of human African trypanomiasis (HAT), transmitting >95% of cases. Traps and insecticide-treated targets are used to control tsetse but more cost-effective baits might be developed through a better understanding of the fly's host-seeking behaviour. Electrocuting grids were used to assess the numbers of G. palpalis palpalis and G. fuscipes quanzensis attracted to and landing on square or oblong targets of black cloth varying in size from 0.01 m(2) to 1.0 m(2). For both species, increasing the size of a square target from 0.01 m(2) (dimensions=0.1 × 0.1 m) to 1.0 m(2) (1.0 × 1.0 m) increased the catch ~4x however the numbers of tsetse killed per unit area of target declined with target size suggesting that the most cost efficient targets are not the largest. For G. f. quanzensis, horizontal oblongs, (1 m wide × 0.5 m high) caught ~1.8x more tsetse than vertical ones (0.5 m wide × 1.0 m high) but the opposite applied for G. p. palpalis. Shape preference was consistent over the range of target sizes. For G. p. palpalis square targets caught as many tsetse as the oblong; while the evidence is less strong the same appears to apply to G. f. quanzensis. The results suggest that targets used to control G. p. palpalis and G. f. quanzensis should be square, and that the most cost-effective designs, as judged by the numbers of tsetse caught per area of target, are likely to be in the region of 0.25 × 0.25 m(2). The preference of G. p. palpalis for vertical oblongs is unique amongst tsetse species, and it is suggested that this response might be related to its anthropophagic behaviour and hence importance as a vector of HAT.