Patterns of gene recombination shape var gene repertoires in Plasmodium falciparum: comparisons of geographically diverse isolates

BACKGROUND: Var genes encode a family of virulence factors known as PfEMP1 (Plasmodium falciparum erythrocyte membrane protein 1) which are responsible for both antigenic variation and cytoadherence of infected erythrocytes. Although these molecules play a central role in malaria pathogenesis, the mechanisms generating variant antigen diversification are poorly understood. To investigate var gene evolution, we compared the variant antigen repertoires from three geographically diverse parasite isolates: the 3D7 genome reference isolate; the recently sequenced HB3 isolate; and the IT4/25/5 (IT4) parasite isolate which retains the capacity to cytoadhere in vitro and in vivo. RESULTS: These comparisons revealed that only two var genes (var1csa and var2csa) are conserved in all three isolates and one var gene (Type 3 var) has homologs in IT4 and 3D7. While the remaining 50 plus genes in each isolate are highly divergent most can be classified into the three previously defined major groups (A, B, and C) on the basis of 5' flanking sequence and chromosome location. Repertoire-wide sequence comparisons suggest that the conserved homologs are evolving separately from other var genes and that genes in group A have diverged from other groups. CONCLUSION: These findings support the existence of a var gene recombination hierarchy that restricts recombination possibilities and has a central role in the functional and immunological adaptation of var genes

Limited Effect of Dietary Saturated Fat on Plasma Saturated Fat in the Context of a Low Carbohydrate Diet

We recently showed that a hypocaloric carbohydrate restricted diet (CRD) had two striking effects: (1) a reduction in plasma saturated fatty acids (SFA) despite higher intake than a low fat diet, and (2) a decrease in inflammation despite a significant increase in arachidonic acid (ARA). Here we extend these findings in 8 weight stable men who were fed two 6-week CRD (12%en carbohydrate) varying in quality of fat. One CRD emphasized SFA (CRD-SFA, 86 g/d SFA) and the other, unsaturated fat (CRD-UFA, 47 g SFA/d). All foods were provided to subjects. Both CRD decreased serum triacylglycerol (TAG) and insulin, and increased LDL-C particle size. The CRD-UFA significantly decreased plasma TAG SFA (27.48 ± 2.89 mol%) compared to baseline (31.06 ± 4.26 mol%). Plasma TAG SFA, however, remained unchanged in the CRD-SFA (33.14 ± 3.49 mol%) despite a doubling in SFA intake. Both CRD significantly reduced plasma palmitoleic acid (16:1n-7) indicating decreased de novo lipogenesis. CRD-SFA significantly increased plasma phospholipid ARA content, while CRD-UFA significantly increased EPA and DHA. Urine 8-iso PGF2α, a free radical-catalyzed product of ARA, was significantly lower than baseline following CRD-UFA (−32%). There was a significant inverse correlation between changes in urine 8-iso PGF2α and PL ARA on both CRD (r = −0.82 CRD-SFA; r = −0.62 CRD-UFA). These findings are consistent with the concept that dietary saturated fat is efficiently metabolized in the presence of low carbohydrate, and that a CRD results in better preservation of plasma ARA

Omega 6 fatty acids for the primary prevention of cardiovascular disease

Background Omega 6 plays a vital role in many physiological functions but there is controversy concerning its effect on cardiovascular disease (CVD) risk. There is conflicting evidence whether increasing or decreasing omega 6 intake results in beneficial effects. Objectives The two primary objectives of this Cochrane review were to determine the effectiveness of: 1. Increasing omega 6 (Linoleic acid (LA), Gamma-linolenic acid (GLA), Dihomo-gamma-linolenic acid (DGLA), Arachidonic acid (AA), or any combination) intake in place of saturated or monounsaturated fats or carbohydrates for the primary prevention of CVD. 2. Decreasing omega 6 (LA, GLA, DGLA, AA, or any combination) intake in place of carbohydrates or protein (or both) for the primary prevention of CVD. Search methods We searched the following electronic databases up to 23 September 2014: the Cochrane Central Register of Controlled Trials (CENTRAL) on the Cochrane Library (Issue 8 of 12, 2014); MEDLINE (Ovid) (1946 to September week 2, 2014); EMBASE Classic and EMBASE (Ovid) (1947 to September 2014); Web of Science Core Collection (Thomson Reuters) (1990 to September 2014); Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment Database, and Health Economics Evaluations Database on the Cochrane Library (Issue 3 of 4, 2014). We searched trial registers and reference lists of reviews for further studies. We applied no language restrictions. Selection criteria Randomised controlled trials (RCTs) of interventions stating an intention to increase or decrease omega 6 fatty acids, lasting at least six months, and including healthy adults or adults at high risk of CVD. The comparison group was given no advice, no supplementation, a placebo, a control diet, or continued with their usual diet. The outcomes of interest were CVD clinical events (all-cause mortality, cardiovascular mortality, non-fatal end points) and CVD risk factors (changes in blood pressure, changes in blood lipids, occurrence of type 2 diabetes). We excluded trials involving exercise or multifactorial interventions to avoid confounding. Data collection and analysis Two review authors independently selected trials for inclusion, extracted the data, and assessed the risk of bias in the included trials. Main results We included four RCTs (five papers) that randomised 660 participants. No ongoing trials were identified. All included trials had at least one domain with an unclear risk of bias. There were no RCTs of omega 6 intake reporting CVD clinical events. Three trials investigated the effect of increased omega 6 intake on lipid levels (total cholesterol, low density lipoprotein (LDL-cholesterol), and high density lipoprotein (HDL-cholesterol)), two trials reported triglycerides, and two trials reported blood pressure (diastolic and systolic blood pressure). Two trials, one with two relevant intervention arms, investigated the effect of decreased omega 6 intake on blood pressure parameters and lipid levels (total cholesterol, LDL-cholesterol, and HDL-cholesterol) and one trial reported triglycerides. Our analyses found no statistically significant effects of either increased or decreased omega 6 intake on CVD risk factors. Two studies were supported by funding from the UK Food Standards Agency and Medical Research Council. One study was supported by Lipid Nutrition, a commercial company in the Netherlands and the Dutch Ministry of Economic Affairs. The final study was supported by grants from the Finnish Food Research Foundation, Finnish Heart Research Foundation, Aarne and Aili Turnen Foundation, and the Research Council for Health, Academy of Finland. Authors’ conclusions We found no studies examining the effects of either increased or decreased omega 6 on our primary outcome CVD clinical endpoints and insufficient evidence to show an effect of increased or decreased omega 6 intake on CVD risk factors such as blood lipids and blood pressure. Very few trials were identified with a relatively small number of participants randomised. There is a need for larger well conducted RCTs assessing cardiovascular events as well as cardiovascular risk factors

Public Sector Reform and Governance for Adaptation: Implications of New Public Management for Adaptive Capacity in Mexico and Norway

Although many governments are assuming the responsibility of initiating adaptation policy in relation to climate change, the compatibility of “governance-for-adaptation” with the current paradigms of public administration has generally been overlooked. Over the last several decades, countries around the globe have embraced variants of the philosophy of administration broadly called “New Public Management” (NPM) in an effort to improve administrative efficiencies and the provision of public services. Using evidence from a case study of reforms in the building sector in Norway, and a case study of water and flood risk management in central Mexico, we analyze the implications of the adoption of the tenets of NPM for adaptive capacity. Our cases illustrate that some of the key attributes associated with governance for adaptation—namely, technical and financial capacities; institutional memory, learning and knowledge; and participation and accountability—have been eroded by NPM reforms. Despite improvements in specific operational tasks of the public sector in each case, we show that the success of NPM reforms presumes the existence of core elements of governance that have often been found lacking, including solid institutional frameworks and accountability. Our analysis illustrates the importance of considering both longer-term adaptive capacities and short-term efficiency goals in public sector administration reform

The need for harmonization and innovation of neuropsychological assessment in neurodegenerative dementias in Europe: consensus document of the Joint Program for Neurodegenerative Diseases Working Group

Cognitive, behavioural, and functional assessment is crucial in longitudinal studies of neurodegenerative dementias (NDD). Central issues, such as the definition of the study population (asymptomatic, at risk, or individuals with dementia), the detection of change/decline, and the assessment of relevant outcomes depend on quantitative measures of cognitive, behavioural, and functional status. Currently, we are far from having available reliable protocols and tools for the assessment of dementias in Europe. The main problems are the heterogeneity of the tools used across different European countries, the lack of standardisation of administration and scoring methods across centres, and the limited information available about the psychometric properties of many tests currently in widespread use. This situation makes it hard to compare results across studies carried out in different centres, thus hampering research progress, in particular towards the contribution to a “big data” common data set. We present here the results of a project funded by the Joint Program for Neurodegenerative Diseases (JPND) and by the Italian Ministry of Health. The project aimed at providing a consensus framework for the harmonisation of assessment tools to be applied to research in neurodegenerative disorders affecting cognition across Europe. A panel of European experts reviewed the current methods of neuropsychological assessment, identified pending issues, and made recommendations for the harmonisation of neuropsychological assessment of neurodegenerative dementias in Europe. A consensus was achieved on the general recommendations to be followed in developing procedures and tools for neuropsychological assessment, with the aim of harmonising tools and procedures to achieve more reliable data on the cognitive-behavioural examination. The results of this study should be considered as a first step to enhancing a common view and practise on NDD assessment across European countries