Changes in the Treatment Responses to Artesunate-Mefloquine on the Northwestern Border of Thailand during 13 Years of Continuous Deployment

Background

Artemisinin combination treatments (ACT) are recommended as first line treatment for falciparum malaria throughout the malaria affected world. We reviewed the efficacy of a 3-day regimen of mefloquine and artesunate regimen (MAS₃), over a 13 year period of continuous deployment as first-line treatment in camps for displaced persons and in clinics for migrant population along the Thai-Myanmar border.

Methods and Findings

3,264 patients were enrolled in prospective treatment trials between 1995 and 2007 and treated with MAS₃. The proportion of patients with parasitaemia persisting on day-2 increased significantly from 4.5% before 2001 to 21.9% since 2002 (p<0.001). Delayed parasite clearance was associated with increased risk of developing gametocytaemia (AOR = 2.29; 95% CI, 2.00–2.69, p = 0.002). Gametocytaemia on admission and carriage also increased over the years (p = 0.001, test for trend, for both). MAS₃ efficacy has declined slightly but significantly (Hazards ratio 1.13; 95% CI, 1.07–1.19, p<0.001), although efficacy in 2007 remained well within acceptable limits: 96.5% (95% CI, 91.0–98.7). The in vitro susceptibility of P. falciparum to artesunate increased significantly until 2002, but thereafter declined to levels close to those of 13 years ago (geometric mean in 2007: 4.2 nM/l; 95% CI, 3.2–5.5). The proportion of infections caused by parasites with increased pfmdr1 copy number rose from 30% (12/40) in 1996 to 53% (24/45) in 2006 (p = 0.012, test for trend).

Conclusion

Artesunate-mefloquine remains a highly efficacious antimalarial treatment in this area despite 13 years of widespread intense deployment, but there is evidence of a modest increase in resistance. Of particular concern is the slowing of parasitological response to artesunate and the associated increase in gametocyte carriage.     

Community Analysis of Chronic Wound Bacteria Using 16S rRNA Gene-Based Pyrosequencing: Impact of Diabetes and Antibiotics on Chronic Wound Microbiota

Background

Bacterial colonization is hypothesized to play a pathogenic role in the non-healing state of chronic wounds. We characterized wound bacteria from a cohort of chronic wound patients using a 16S rRNA gene-based pyrosequencing approach and assessed the impact of diabetes and antibiotics on chronic wound microbiota.

Methodology/Principal Findings

We prospectively enrolled 24 patients at a referral wound center in Baltimore, MD; sampled patients'' wounds by curette; cultured samples under aerobic and anaerobic conditions; and pyrosequenced the 16S rRNA V3 hypervariable region. The 16S rRNA gene-based analyses revealed an average of 10 different bacterial families in wounds—approximately 4 times more than estimated by culture-based analyses. Fastidious anaerobic bacteria belonging to the Clostridiales family XI were among the most prevalent bacteria identified exclusively by 16S rRNA gene-based analyses. Community-scale analyses showed that wound microbiota from antibiotic treated patients were significantly different from untreated patients (p = 0.007) and were characterized by increased Pseudomonadaceae abundance. These analyses also revealed that antibiotic use was associated with decreased Streptococcaceae among diabetics and that Streptococcaceae was more abundant among diabetics as compared to non-diabetics.

Conclusions/Significance

The 16S rRNA gene-based analyses revealed complex bacterial communities including anaerobic bacteria that may play causative roles in the non-healing state of some chronic wounds. Our data suggest that antimicrobial therapy alters community structure—reducing some bacteria while selecting for others.     

Estimating and conserving patterns of invertebrate diversity: a test case of New Zealand land snails

Aim Using New Zealand land snails as a case study, we evaluated recent spatial modelling approaches for the analysis of diversity in species‐rich invertebrate groups. Applications and prospects for improved conservation assessment were investigated. Location New Zealand. Methods The study used a spatially extensive and taxonomically comprehensive, plot‐based dataset on community structure in New Zealand land snails. Generalized regression analysis and spatial prediction (GRASP) was used to model and predict species richness as a function of environmental variables (including aspects of climate, soils and vegetation). Generalized dissimilarity modelling (GDM) was used to model turnover in species composition in relation to environmental and geographical distances, and to assess community similarity and the representativeness of the reserve network. Results Observed land snail richness in 20 × 20 m plots ranged from 1 to 74 (mean 17.5). The GRASP model explained a modest 27% of the variation in richness. The GDM model explained 57% of the variation in species turnover and indicated approximately equal amounts related to environmental (Cody’s beta diversity) and geographical distance (Cody’s gamma diversity). Temperature and moisture were the most important environmental variables. Results indicate that snail distributions are not only sorted by environment but are also strongly influenced by historical effects consistent with those expected of poorly dispersing taxa that have persisted in refugia during past climatic change. The GDM model enabled spatial classifications of snail communities, highlighting diverse communities in heterogeneous regions, such as the South Island mountains, and also enabled continuous depictions of community similarity and adequacy of New Zealand’s protected natural areas network. Main conclusions The GRASP and GDM analyses allowed us to model and depict spatial patterns of diversity in land snail communities involving 845 species, and produce community classifications and estimates of community similarity. These tools advance conservation assessment in species‐rich groups, but require further conceptual and methodological development.     

A database of vertebrate longevity records and their relation to other life‐history traits

Longevity is a major characteristic of animals that has long fascinated scientists. In this work, we present a comprehensive database of animal longevity records and related life‐history traits entitled AnAge, which we compiled and manually curated from an extensive literature. AnAge started as a collection of longevity records, but has since been expanded to include quantitative data for numerous other life‐history traits, including body masses at different developmental stages, reproductive data such as age at sexual maturity and measurements of reproductive output, and physiological traits related to metabolism. AnAge features over 4000 vertebrate species and is a central resource for applying the comparative method to studies of longevity and life‐history evolution across the tree of life. Moreover, by providing a reference value for longevity and other life‐history traits, AnAge can prove valuable to a broad range of biologists working in evolutionary biology, ecology, zoology, physiology and conservation biology. AnAge is freely available online ( http://genomics.senescence.info/species/ ).     

Pathogenic bacteria and TNF do not induce production of macrophage migration inhibitory factor (MIF) by human monocytes

Elevated serum macrophage migration inhibitory factor (MIF) is associated with severe sepsis, but it is not clear whether bacteria stimulate synthesis of MIF by blood leukocytes directly or via induction of TNF. Here we assess production of MIF mRNA and protein by blood leukocytes from healthy human subjects (n = 28) following exposure to bacteria commonly associated with sepsis (Escherichia coli and Streptococcus pneumoniae). Bacteria did not increase levels of MIF mRNA or secreted protein. CD14⁺ monocytes were the main cell type producing MIF before and after stimulation. Exposure of leukocytes to TNF did not induce MIF. Hence elevated levels of serum MIF observed in sepsis may not reflect MIF produced by blood leukocytes stimulated directly by bacteria or TNF.     

Tissue-targeted metabonomics: biological considerations and application to doxorubicin-induced hepatic oxidative stress

Tissue-targeted metabonomics, or the use of microdialysis sampling with NMR detection, can be used to monitor the metabolic profiles of specific tissues without the need to take tissue biopsies. This allows for sampling from the same animal over the time course of the experiment, reducing animal-to-animal variability and decreasing the number of animals required, however, this approach to metabonomics studies has not been fully characterized. In this work liver microdialysis sampling was performed on male Sprague–Dawley rats and the effects of diurnal rhythms, animal activity and anesthesia on the liver extracellular fluid composition examined. Diurnal rhythms and animal activity caused little change in liver metabolism, but anesthesia caused dramatic effects attributed to the hyperglycemia induced by xylazine and isoflurane. This approach was then applied to the characterization of the hepatotoxicity of doxorubicin, an anticancer agent known to induce oxidative stress. In these studies, two probes were implanted in the liver and doxorubicin was dosed through one of the probes. Comparisons were made between the metabolic profiles from the two probes to distinguish basal metabolic effects from those induced by doxorubicin. Doxorubicin altered hepatic metabolism by different mechanisms in anesthetized and awake rats. These studies also provided important implications for the design of future tissue-targeted metabonomics experiments.     

Asexual sporulation signalling regulates autolysis of Aspergillus nidulans via modulating the chitinase ChiB production

Aims:  Elucidation of the regulation of ChiB production in Aspergillus nidulans .
Methods and Results:  Mutational inactivation of the A. nidulans chiB gene resulted in a nonautolytic phenotype. To better understand the mechanisms controlling both developmental progression and fungal autolysis, we examined a range of autolysis-associated parameters in A. nidulans developmental and/or autolytic mutants. Investigation of disorganization of mycelial pellets, loss of biomass, extra-/intracellular chitinase activities, ChiB production and chiB mRNA levels in various cultures revealed that, in submerged cultures, initialization of autolysis and stationary phase-induced ChiB production are intimately coupled, and that both processes are controlled by the FluG-BrlA asexual sporulation regulatory pathway. ChiB production does not affect the progression of apoptotic cell death in the aging A. nidulans cultures.
Conclusions:  The endochitinase ChiB plays an important role in autolysis of A. nidulans , and its production is initiated by FluG-BrlA signalling. Despite the fact that apoptosis is an inseparable part of fungal autolysis, its regulation is independent to FluG-initiated sporulation signalling.
Significance and Impact of the Study:  Deletion of chiB and fluG homologues in industrial filamentous fungal strains may stabilize the hyphal structures in the autolytic phase of growth and limit the release of autolytic hydrolases into the culture medium.     

The Impact of Divergence Time on the Nature of Population Structure: An Example from Iceland

The Icelandic population has been sampled in many disease association studies, providing a strong motivation to understand the structure of this population and its ramifications for disease gene mapping. Previous work using 40 microsatellites showed that the Icelandic population is relatively homogeneous, but exhibits subtle population structure that can bias disease association statistics. Here, we show that regional geographic ancestries of individuals from Iceland can be distinguished using 292,289 autosomal single-nucleotide polymorphisms (SNPs). We further show that subpopulation differences are due to genetic drift since the settlement of Iceland 1100 years ago, and not to varying contributions from different ancestral populations. A consequence of the recent origin of Icelandic population structure is that allele frequency differences follow a null distribution devoid of outliers, so that the risk of false positive associations due to stratification is minimal. Our results highlight an important distinction between population differences attributable to recent drift and those arising from more ancient divergence, which has implications both for association studies and for efforts to detect natural selection using population differentiation.     

A computationally inspired investigation of the solid forms of (R)‐1‐phenylethylammonium‐(S)‐2‐phenylbutyrate

Following the computation of a lattice energy landscape which predicted that there should be more stable, denser forms of (R)‐1‐phenylethylammonium‐(S)‐2‐phenylbutyrate, crystallizations from a range of solvents were performed to search for other polymorphs and investigate the possibility that the known P4₁ structure could be a hydrate. Extensive crystallization experiments from a wide range of solvents gave fine needles or microcrystalline samples. A redetermination of the P4₁ structure by powder X‐ray diffraction located all protons, and in conjunction with other experimental and computational evidence showed that the structure was anhydrous. Evidence for two additional forms was found as mixtures with form I. These include an orthorhombic form, possibly a Z′ = 3 polymorph, and another as yet unidentified form obtained as a minor component from dichloromethane solution. However, both these forms appear to be metastable with respect to form I (P4₁), which is therefore probably the most thermodynamically stable form that can be crystallized from solution under ambient conditions. This determination of the solid state behavior of the less readily crystallized member of the diastereomeric salt system (R)‐1‐phenylethylammonium‐(R/S)‐2‐phenylbutyrate provides a challenge to the theoretical modeling to explain its ideal resolution behavior. Chirality 2010. © 2009 Wiley‐Liss, Inc.     

Blogging Anthropology: Savage Minds, Zero Anthropology, and AAA Blogs

ABSTRACT  In this review essay, the academic merits of three anthropological blogs ("Savage Minds,""Zero Anthropology"[formerly "Open Anthropology"], and the official blog of the American Anthropological Association) are considered. The review examines differences between group-blog projects (such "Savage Minds"), single-voiced blogs (such as "Zero Anthropology"), and official blogs representing central anthropological institutions (the AAA's blog) and identifies roles and strengths of each of these blog forms.