26 research outputs found

    Agroecology and the Struggle for Food Sovereignty in the Americas

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    A collaborative project of the International Institute for Environment and Development (IIED), the IUCN Commission on Environmental, Economic and Social Policy (CEESP) and the Yale School of Forestry & Environmental Studies (Yale F&ES

    Peanut‐induced anaphylaxis in children and adolescents: Data from the European Anaphylaxis Registry

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    Background Peanut allergy has a rising prevalence in high-income countries, affecting 0.5%-1.4% of children. This study aimed to better understand peanut anaphylaxis in comparison to anaphylaxis to other food triggers in European children and adolescents. Methods Data was sourced from the European Anaphylaxis Registry via an online questionnaire, after in-depth review of food-induced anaphylaxis cases in a tertiary paediatric allergy centre. Results 3514 cases of food anaphylaxis were reported between July 2007 - March 2018, 56% in patients younger than 18 years. Peanut anaphylaxis was recorded in 459 children and adolescents (85% of all peanut anaphylaxis cases). Previous reactions (42% vs. 38%; p = .001), asthma comorbidity (47% vs. 35%; p < .001), relevant cofactors (29% vs. 22%; p = .004) and biphasic reactions (10% vs. 4%; p = .001) were more commonly reported in peanut anaphylaxis. Most cases were labelled as severe anaphylaxis (Ring&Messmer grade III 65% vs. 56% and grade IV 1.1% vs. 0.9%; p = .001). Self-administration of intramuscular adrenaline was low (17% vs. 15%), professional adrenaline administration was higher in non-peanut food anaphylaxis (34% vs. 26%; p = .003). Hospitalization was higher for peanut anaphylaxis (67% vs. 54%; p = .004). Conclusions The European Anaphylaxis Registry data confirmed peanut as one of the major causes of severe, potentially life-threatening allergic reactions in European children, with some characteristic features e.g., presence of asthma comorbidity and increased rate of biphasic reactions. Usage of intramuscular adrenaline as first-line treatment is low and needs to be improved. The Registry, designed as the largest database on anaphylaxis, allows continuous assessment of this condition

    Targeting NAD<sup>+</sup> Metabolism in the Human Malaria Parasite <i>Plasmodium falciparum</i>

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    <div><p>Nicotinamide adenine dinucleotide (NAD<sup>+</sup>) is an essential metabolite utilized as a redox cofactor and enzyme substrate in numerous cellular processes. Elevated NAD<sup>+</sup> levels have been observed in red blood cells infected with the malaria parasite <i>Plasmodium falciparum</i>, but little is known regarding how the parasite generates NAD<sup>+</sup>. Here, we employed a mass spectrometry-based metabolomic approach to confirm that <i>P. falciparum</i> lacks the ability to synthesize NAD<sup>+</sup><i>de novo</i> and is reliant on the uptake of exogenous niacin. We characterized several enzymes in the NAD<sup>+</sup> pathway and demonstrate cytoplasmic localization for all except the parasite nicotinamidase, which concentrates in the nucleus. One of these enzymes, the <i>P. falciparum</i> nicotinate mononucleotide adenylyltransferase (PfNMNAT), is essential for NAD<sup>+</sup> metabolism and is highly diverged from the human homolog, but genetically similar to bacterial NMNATs. Our results demonstrate the enzymatic activity of PfNMNAT <i>in vitro</i> and demonstrate its ability to genetically complement the closely related <i>Escherichia coli</i> NMNAT. Due to the similarity of PfNMNAT to the bacterial enzyme, we tested a panel of previously identified bacterial NMNAT inhibitors and synthesized and screened twenty new derivatives, which demonstrate a range of potency against live parasite culture. These results highlight the importance of the parasite NAD<sup>+</sup> metabolic pathway and provide both novel therapeutic targets and promising lead antimalarial compounds.</p></div

    Recommendations for the Long-Term Treatment of Psoriasis with Infliximab: A Dermatology Expert Group Consensus

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    Background/Aims: Infliximab has been approved for the treatment of chronic plaque psoriasis for only a few years. As physicians gain confidence in initiating and maintaining this therapy, guidance on the management of patients beyond several months or years is needed. To date, there is little or no information about the long-term management in clinical trials or guidelines. Methods: Here we report on the key aspects related to the use of infliximab for the treatment of psoriasis. The data presented here were derived using a modified Delphi survey to obtain a consensus opinion of 11 dermatologists from Europe and Canada experienced in long-term therapy with infliximab. Results/Conclusion: The Delphi participants reviewed several important topics relat- ed to biological therapy and infliximab. This paper is not intended to provide a recommendation on all practical aspects related to biological therapy; it has rather been written to provide useful and practical information on the ‘best practice’ use of infliximab

    PF13_0159 encodes a nicotinate mononucleotide adenylyltransferase.

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    <p><b>A</b>. Dependence of PF13_0159 adenylyltransferase activity on time and enzyme concentration. A discontinuous assay was established to measure enzyme activity; pyrophosphate release is measured as the end product of the adenylyltransferase reaction. Values were normalized to background absorbance values obtained in a buffer only control. A standard curve was generated to determine pyrophosphate concentrations. Error is reported at the SD of three independent technical replicates. <b>B</b>. Phylogenic analysis of PF13_0159 compared to representative prokaryotic and eukaryotic NMNATs. ClustalW2 was used to generate alignments and distance values are reported. An alignment of PF13_0159 and the <i>E. coli</i> NADD is shown in Figure S5 (in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094061#pone.0094061.s001" target="_blank">File S1</a>).</p

    Inhibitory effect of putative NMNAT inhibitors <i>in vitro</i>.

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    <p><b>A</b>. 1a-a inhibits adenylyltransferase activity of PfNMNAT. Purified enzyme was preincubated with either 50 µM 1a-a or 2% of DMSO for ten minutes before pyrophosphate release was monitored continuously at 565 nm. A standard curve of pyrophosphate was used to determine concentration from observed absorbance values. Error is reported at the SD of three independent technical replicates. <b>B</b>. MIC<sub>50</sub> curve for 1a-a. A standard SYBR green growth assay was performed on synchronous ring stage parasites to determine MIC<sub>50</sub> (See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094061#s4" target="_blank">Material and Methods</a>). Error is reported as the SD of three independent biological replicates. <b>C</b>. Imaging of <i>P. falciparum</i> treated with 50 µM of 1a-a or a 1% DMSO control. Parasite growth was monitored by imaging of fixed parasites visualized with Giemsa stain.</p

    Antimalarial activity and partition coefficients for putative NMNAT inhibitors.

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    <p>MIC<sub>50</sub> values were determined for each synthesized NMNAT inhibitor using a standard SYBR green growth assay on synchronous ring stage parasites. Error is reported as the SD of three independent biological replicates. *Calculated octanol/water partition coefficients (cLogPs) for all compounds were determined using online tools at <a href="http://www.molinspiration.com" target="_blank">http://www.molinspiration.com</a>.</p

    <i>Plasmodium falciparum</i> NAD<sup>+</sup> metabolism.

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    <p><b>A</b>. Overview of the NAD<sup>+</sup> salvage pathways in <i>Plasmodium</i> parasites and the human host red blood cell. Plasmodium falciparum gene IDs and mammalian gene names are presented for each enzyme in italics. The red blood cell is shown in red, the parasitophorous membrane is shown in grey and the parasite membrane is shown in black. Na: nicotinic acid; Nam: nicotinamide; NR: nicotinamide ribotide; NaMN: nicotinate mononucleotide; NMN: nicotinamide mononucleotide; NaAD: nicotinate adenine dinucleotide; NAD<sup>+</sup>: nicotinamide adenine dinucleotide. NAPRT: nicotinic acid phosphoribosyltransferase, NMNAT: mononucleotide adenylyl transferase, NRK: nicotinamide riboside kinase, NP: nucleoside phosphorylase, NAMPT: nicotinamide phosphoribosyltransferase <b>B</b>. Live imaging of episomally expressed GFP tagged NAD<sup>+</sup> metabolic enzymes are shown (GFP-fusion proteins are shown in green). Enzyme Commission numbers are provided for each enzyme. All images are of trophozoite stage parasites. Hoechst dye (shown in blue) was used to visualize the parasite nucleus. *For example: sirtuins and poly(ADP-ribose) polymerases.</p
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