Iron status predicts malaria risk in malawian preschool children

Introduction

Iron deficiency is highly prevalent in pre-school children in developing countries and an important health problem in sub-Saharan Africa. A debate exists on the possible protective effect of iron deficiency against malaria and other infections; yet consensus is lacking due to limited data. Recent studies have focused on the risks of iron supplementation but the effect of an individual''s iron status on malaria risk remains unclear. Studies of iron status in areas with a high burden of infections often are exposed to bias. The aim of this study was to assess the predictive value of baseline iron status for malaria risk explicitly taking potential biases into account.

Methods and materials

We prospectively assessed the relationship between baseline iron deficiency (serum ferritin <30 µg/L) and malaria risk in a cohort of 727 Malawian preschool children during a year of follow-up. Data were analyzed using marginal structural Cox regression models and confounders were selected using causal graph theory. Sensitivity of results to bias resulting from misclassification of iron status by concurrent inflammation and to bias from unmeasured confounding were assessed using modern causal inference methods.

Results and Conclusions

The overall incidence of malaria parasitemia and clinical malaria was 1.9 (95% CI 1.8–2.0) and 0.7 (95% CI 0.6–0.8) events per person-year, respectively. Children with iron deficiency at baseline had a lower incidence of malaria parasitemia and clinical malaria during a year of follow-up; adjusted hazard ratio''s 0.55 (95%-CI:0.41–0.74) and 0.49 (95%-CI:0.33–0.73), respectively. Our results suggest that iron deficiency protects against malaria parasitemia and clinical malaria in young children. Therefore the clinical importance of treating iron deficiency in a pre-school child should be weighed carefully against potential harms. In malaria endemic areas treatment of iron deficiency in children requires sustained prevention of malaria.     

Blind testing of routine, fully automated determination of protein structures from NMR data

The protocols currently used for protein structure determination by nuclear magnetic resonance (NMR) depend on the determination of a large number of upper distance limits for proton-proton pairs. Typically, this task is performed manually by an experienced researcher rather than automatically by using a specific computer program. To assess whether it is indeed possible to generate in a fully automated manner NMR structures adequate for deposition in the Protein Data Bank, we gathered 10 experimental data sets with unassigned nuclear Overhauser effect spectroscopy (NOESY) peak lists for various proteins of unknown structure, computed structures for each of them using different, fully automatic programs, and compared the results to each other and to the manually solved reference structures that were not available at the time the data were provided. This constitutes a stringent "blind" assessment similar to the CASP and CAPRI initiatives. This study demonstrates the feasibility of routine, fully automated protein structure determination by NMR.     

The assessment of competence in cognitively impaired elderly persons: a closer look at the vignette method

This article focuses on the assessment of competence of elderly persons both with and without cognitive impairment. In total 113 patients of a geriatric clinic were interviewed. Competence was assessed by using two clinical vignettes, representing respectively a hypothetical treatment situation with mild consequences (endoscopy) and one with severe consequences (operation for colon cancer). Competence was evaluated using the following standards: the ability to evidence a choice, the ability to understand a situation, the ability to reason about a choice, and the ability to appreciate a situation. In the vignette with mild consequences, elderly persons with cognitive impairment performed significantly worse on understanding, reasoning and appreciation than elderly persons without cognitive impairment. In the vignette with severe consequences, elderly persons with cognitive impairment performed significantly worse only on understanding as compared to elderly persons without cognitive impairment. No differences were found for reasoning and appreciation between the cognitively impaired and non-impaired elderly persons. We conclude that competence is less limited by cognitive impairment when assessed in a treatment situation with severe consequences. Therefore, the use of hypothetical vignettes should be carefully reconsidered.     

Endoglin promotes endothelial cell proliferation and TGF-beta/ALK1 signal transduction

Endoglin is a transmembrane accessory receptor for transforming growth factor-beta (TGF-beta) that is predominantly expressed on proliferating endothelial cells in culture and on angiogenic blood vessels in vivo. Endoglin, as well as other TGF-beta signalling components, is essential during angiogenesis. Mutations in endoglin and activin receptor-like kinase 1 (ALK1), an endothelial specific TGF-beta type I receptor, have been linked to the vascular disorder, hereditary haemorrhagic telangiectasia. However, the function of endoglin in TGF-beta/ALK signalling has remained unclear. Here we report that endoglin is required for efficient TGF-beta/ALK1 signalling, which indirectly inhibits TGF-beta/ALK5 signalling. Endothelial cells lacking endoglin do not grow because TGF-beta/ALK1 signalling is reduced and TGF-beta/ALK5 signalling is increased. Surviving cells adapt to this imbalance by downregulating ALK5 expression in order to proliferate. The ability of endoglin to promote ALK1 signalling also explains why ectopic endoglin expression in endothelial cells promotes proliferation and blocks TGF-beta-induced growth arrest by indirectly reducing TGF-beta/ALK5 signalling. Our results indicate a pivotal role for endoglin in the balance of ALK1 and ALK5 signalling to regulate endothelial cell proliferation.     

(+/-)-Schefflone: a trimeric monoterpenoid from the root bark of Uvaria scheffleri

The trimeric monoterpene and mildly mosquito larvicidal agent, (+/-)-schefflone, that is an apparent derivative of the antiparasitic aromatic monoterpene espintanol, was isolated from the antimalarial extracts of the root bark of Uvaria scheffleri, together with espintanol. Structural determination of (+/-)-schefflone was achieved from spectroscopic data and confirmed by single-crystal X-ray diffraction analysis. (+/-)-Schefflone can be considered a product of a non-enzymatic Diels-Alder-type cycloaddition reaction of the quinonemethide derivative of espintanol as the diene and dienophile.     

The light-hyperresponsive high pigment-2dg mutation of tomato: alterations in the fruit metabolome

Overall metabolic modifications between fruit of light-hyperresponsive high-pigment (hp) tomato (Lycopersicon esculentum) mutant plants and isogenic nonmutant (wt) control plants were compared. Targeted metabolite analyses, as well as large-scale nontargeted mass spectrometry (MS)-based metabolite profiling, were used to phenotype the differences in fruit metabolite composition. Targeted high-performance liquid chromatography with photodiode array detection (HPLC-PDA) metabolite analyses showed higher levels of isoprenoids and phenolic compounds in hp-2dg fruit. Nontargeted GC-MS profiling of red fruits produced 25 volatile compounds that showed a 1.5-fold difference between the genotypes. Analyses of red fruits using HPLC coupled to high-resolution quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) in both ESI-positive and ESI-negative mode generated, respectively, 6168 and 5401 mass signals, of which 142 and 303 showed a twofold difference between the genotypes. hp-2dg fruits are characterized by overproduction of many metabolites, several of which are known for their antioxidant or photoprotective activities. These metabolites may now be more closely implicated as resources recruited by plants to respond to and manage light stress. The similarity in metabolic alterations in fruits of hp-1 and hp-2 mutant plants helps us to understand how hp mutations affect cellular processes.     

The breast cancer resistance protein BCRP (ABCG2) concentrates drugs and carcinogenic xenotoxins into milk

Contamination of milk with drugs, pesticides and other xenotoxins can pose a major health risk to breast-fed infants and dairy consumers. Here we show that the multidrug transporter BCRP (encoded by ABCG2) is strongly induced in the mammary gland of mice, cows and humans during lactation and that it is responsible for the active secretion of clinically and toxicologically important substrates such as the dietary carcinogen PhIP, the anticancer drug topotecan and the antiulcerative cimetidine into mouse milk.