Low antibodies against Plasmodium falciparum and imbalanced pro-inflammatory cytokines are associated with severe malaria in Mozambican children: a case-control study

ABSTRACT: BACKGROUND: The factors involved in the progression from Plasmodium falciparum infection to severe malaria (SM) are still incompletely understood. Altered antibody and cellular immunity against P. falciparum might contribute to increase the risk of developing SM. METHODS: To identify immune responses associated with SM, a sex- and age-matched case-control study was carried out in 134 Mozambican children with SM (cerebral malaria, severe anaemia, acidosis and/or respiratory distress, prostration, hypoglycaemia, multiple seizures) or uncomplicated malaria (UM). IgG and IgM against P. falciparum lysate, merozoite antigens (MSP-119, AMA-1 and EBA-175), a Duffy binding like (DBL)-alpha rosetting domain and antigens on the surface of infected erythrocytes were measured by ELISA or flow cytometry. Plasma concentrations of IL-12p70, IL-2, IFN-gamma, IL-4, IL-5, IL-10, IL-8, IL-6, IL- 1beta, TNF, TNF-beta and TGF-beta1 were measured using fluorescent bead immunoassays. Data was analysed using McNemar's and Signtest. RESULTS: Compared to UM, matched children with SM had reduced levels of IgG against DBLalpha (P < 0.001), IgM against MSP-119 (P = 0.050) and AMA-1 (P = 0.047), TGF-beta1 (P <0.001) and IL-12 (P = 0.039). In addition, levels of IgG against P. falciparum lysate and IL-6 concentrations were increased (P = 0.004 and P = 0.047, respectively). Anti-DBLalpha IgG was the only antibody response associated to reduced parasite densities in a multivariate regression model (P = 0.026). CONCLUSIONS: The lower levels of antibodies found in children with SM compared to children with UM were not attributable to lower exposure to P. falciparum in the SM group. IgM against P. falciparum and specific IgG against a rosetting PfEMP1 domain may play a role in the control of SM, whereas an imbalanced pro-inflammatory cytokine response may exacerbate the severity of infection. A high overlap in symptoms together with a limited sample size of different SM clinical groups reduced the power to identify immunological correlates for particular forms of SM.     

Maternal mental health and its association with infant growth at 6 months in ethnic groups: results from the Born-in-Bradford birth cohort study

Objective

To identify factors associated with infant growth up to 6 months, with a particular focus on maternal distress, and to explore the effect of ethnicity on any relation between maternal distress and infant growth.

Methods

Cohort study recruiting White and Pakistani women in the United Kingdom (UK). Infant growth was measured at birth and 6 months. Standard assessment of mental health (GHQ-28) was undertaken in pregnancy (26–28 weeks gestation) and 6 months postpartum. Modelling included social deprivation, ethnicity, and other known influences on infant growth such as maternal smoking and alcohol consumption.

Results

Maternal distress improved markedly from pregnancy to 6 months postpartum. At both times Pakistani women had more somatic and depression symptoms than White women. Depression in pregnancy (GHQ subscale D) was associated with lower infant growth at 6 months. Self-reported social dysfunction in pregnancy (GHQ subscale C) was associated with lower gestational age.. Pakistani women reported higher GHQ scores during pregnancy associated with smaller infants at birth. They lived in areas of higher social deprivation, reported less alcohol consumption and smoking postnatally, all independent influences on growth at 6 months.

Conclusions

Maternal mental health in pregnancy is an independent influence on infant growth up to 6 months and is associated with ethnicity which was itself associated with deprivation in our sample. There is a complex relationship between symptoms of maternal distress, ethnicity, deprivation, health behaviours, and early infant growth. Measures should include both emotional and somatic symptoms and interventions to reduce risks of poor early growth need to include psychological and social components.     

Ammonium enhances resistance to salinity stress in citrus plants

In this work, we demonstrate that NH?? nutrition in citrange Carrizo plants acts as an inducer of resistance against salinity conditions. We investigated its mode of action and provide evidence that NH?? confers resistance by priming abscisic acid and polyamines, and enhances H?O? and proline basal content. Moreover, we observed reduced Cl? uptake as well as enhanced PHGPx expression after salt stress. Control and N-NH?? plants showed optimal growth. However, N-NH?? plants displayed greater dry weight and total lateral roots than control plants, but these differences were not observed for primary root length. Our results revealed that N-NH?? treatment induces a similar phenotypical response to the recent stress-induced morphogenetic response (SIMRs). The hypothesis is that N-NH?? treatment triggers mild chronic stress in citrange Carrizo plants, which might explain the SIMR observed. Moreover, we observed modulators of stress signaling, such as H?O? in N-NH?? plants, which could acts as an intermediary between stress and the development of the SIMR phenotype. This observation suggests that NH?? treatments induce a mild stress condition that primes the citrange Carrizo defense response by stress imprinting and confers protection against subsequent salt stress.     

Dietary Intake of Metals by the Population of Tarragona County (Catalonia,Spain): Results from a Duplicate Diet Study

The daily intakes of arsenic (As), beryllium, cadmium (Cd), cobalt, chromium, copper, mercury (Hg), manganese, nickel, lead (Pb), antimony, tin, thallium, uranium, vanadium, and zinc by an adult population living in Tarragona County (Catalonia, Spain) were determined by the duplicate diet method with a 10-day sampling period. Duplicate diet samples, prepared as per consumption, were collected during September 2010 in 20 restaurants offering a variety of daily menus (breakfast, lunch, and dinner). A total of 200 composite samples, corresponding to 600 individual samples, were prepared for trace elements analyses, which were carried out by inductively coupled plasma mass spectrometry. The results were compared with data from previous total diet studies (TDS) recently performed in the same geographical area. Notable differences in the intake of the toxic elements As, Cd, Hg, and Pb were found depending on the method used. It is concluded that both the duplicate diet method and the TDS may provide important and useful information to estimate human exposure to metals through the diet and their derived health risks. However, for comparison between surveys or for establishing temporal trends in the intake of metals, it seems to be recommendable to use always the same method. Notwithstanding, if the interest is only to know whether the intake of a certain element is below the tolerable intake, both methods are useful.     

Predictors of Chronic Trauma-Related Symptoms in a Community Sample of New Zealand Motor Vehicle Accident Survivors

This study examined 1,500 New Zealand community-residing adults for involvement in serious motor vehicle accident (MVA) and the development of trauma-related symptomatology. The incidence of MVA was 11 %. More than 50 % of the accident victim sub-sample reported hyperarousal, with exaggerated startle, intrusive recollections, situational avoidance, emotional reactivity, and cognitive avoidance. The high incidence of trauma-related symptoms is noteworthy given 59 % of victims reported sustaining no or mild accident injury, and only 27 % were admitted to hospital for severe injury. Trauma-related symptoms were related to measures of injury severity, psychological and social functioning, and persistent medical problems. Pre- and post-accident factors, that is, experience of additional trauma, experience of stressful life events and post-accident social contact were the most important predictors of trauma-related symptoms severity. This study discusses the importance of examining trauma-related symptoms rather than using categorical diagnostic criteria (i.e., post-traumatic stress disorder, PTSD) as a sole means of characterizing the psychological impact of MVA.     

Behavior and target site selection of conjugative transposon Tn916 in two different strains of toxigenic Clostridium difficile

The insertion sites of the conjugative transposon Tn916 in the anaerobic pathogen Clostridium difficile were determined using Illumina Solexa high-throughput DNA sequencing of Tn916 insertion libraries in two different clinical isolates: 630ΔE, an erythromycin-sensitive derivative of 630 (ribotype 012), and the ribotype 027 isolate R20291, which was responsible for a severe outbreak of C. difficile disease. A consensus 15-bp Tn916 insertion sequence was identified which was similar in both strains, although an extended consensus sequence was observed in R20291. A search of the C. difficile 630 genome showed that the Tn916 insertion motif was present 100,987 times, with approximately 63,000 of these motifs located in genes and 35,000 in intergenic regions. To test the usefulness of Tn916 as a mutagen, a functional screen allowed the isolation of a mutant. This mutant contained Tn916 inserted into a gene involved in flagellar biosynthesis.     

Sphingosine mediates TNFα-induced lysosomal membrane permeabilization and ensuing programmed cell death in hepatoma cells

Normally, cell proliferation and death are carefully balanced in higher eukaryotes, but one of the most important regulatory mechanisms, apoptosis, is upset in many malignancies, including hepatocellular-derived ones. Therefore, reinforcing cell death often is mandatory in anticancer therapy. We previously reported that a combination of tumor necrosis factor-α (TNF) and cycloheximide (CHX) efficiently kill HTC cells, a rat hepatoma line, in an apoptosis-like mode. Death is actively mediated by the lysosomal compartment, although lysosomal ceramide was previously shown not to be directly implicated in this process. In the present study, we show that TNF/CHX increase lysosomal ceramide that is subsequently converted into sphingosine. Although ceramide accumulation does not significantly alter the acidic compartment, the sphingosine therein generated causes lysosomal membrane permeabilization (LMP) followed by relocation of lysosomal cathepsins to the cytoplasm. TNF/CHX-induced LMP is effectively abrogated by siRNAs targeting acid sphingomyelinase or acid ceramidase, which prevent both LMP and death induced by TNF/CHX. Taken together, our results demonstrate that lysosomal accumulation of ceramide is not detrimental per se, whereas its degradation product sphingosine, which has the capacity to induce LMP, appears responsible for the observed apoptotic-like death.