Validation of the Emergency Department-Paediatric Early Warning Score (ED-PEWS) for use in low- and middle-income countries:A multicentre observational study

Early recognition of children at risk of serious illness is essential in preventing morbidity and mortality, particularly in low- and middle-income countries (LMICs). This study aimed to validate the Emergency Department-Paediatric Early Warning Score (ED-PEWS) for use in acute care settings in LMICs. This observational study is based on previously collected clinical data from consecutive children attending four diverse settings in LMICs. Inclusion criteria and study periods (2010–2021) varied. We simulated the ED-PEWS, consisting of patient age, consciousness, work of breathing, respiratory rate, oxygen saturation, heart rate, and capillary refill time, based on the first available parameters. Discrimination was assessed by the area under the curve (AUC), sensitivity and specificity (previously defined cut-offs &lt; 6 and ≥ 15). The outcome measure was for each setting a composite marker of high urgency. 41,917 visits from Gambia rural, 501 visits from Gambia urban, 2,608 visits from Suriname, and 1,682 visits from Tanzania were included. The proportion of high urgency was variable (range 4.6% to 24.9%). Performance ranged from AUC 0.80 (95%CI 0.70–0.89) in Gambia urban to 0.62 (95%CI 0.55–0.67) in Tanzania. The low-urgency cut-off showed a high sensitivity in all settings ranging from 0.83 (95%CI 0.81–0.84) to 1.00 (95%CI 0.97–1.00). The high-urgency cut-off showed a specificity ranging from 0.71 (95%CI 0.66–0.75) to 0.97 (95%CI 0.97–0.97). The ED-PEWS has a moderate to good performance for the recognition of high urgency children in these LMIC settings. The performance appears to have potential in improving the identification of high urgency children in LMICs.</p

Pleosporales

One hundred and five generic types of Pleosporales are described and illustrated. A brief introduction and detailed history with short notes on morphology, molecular phylogeny as well as a general conclusion of each genus are provided. For those genera where the type or a representative specimen is unavailable, a brief note is given. Altogether 174 genera of Pleosporales are treated. Phaeotrichaceae as well as Kriegeriella, Zeuctomorpha and Muroia are excluded from Pleosporales. Based on the multigene phylogenetic analysis, the suborder Massarineae is emended to accommodate five families, viz. Lentitheciaceae, Massarinaceae, Montagnulaceae, Morosphaeriaceae and Trematosphaeriaceae

A class-wide phylogenetic assessment of Dothideomycetes

We present a comprehensive phylogeny derived from 5 genes, nucSSU, nucLSU rDNA, TEF1, RPB1 and RPB2, for 356 isolates and 41 families (six newly described in this volume) in Dothideomycetes. All currently accepted orders in the class are represented for the first time in addition to numerous previously unplaced lineages. Subclass Pleosporomycetidae is expanded to include the aquatic order Jahnulales. An ancestral reconstruction of basic nutritional modes supports numerous transitions from saprobic life histories to plant associated and lichenised modes and a transition from terrestrial to aquatic habitats are confirmed. Finally, a genomic comparison of 6 dothideomycete genomes with other fungi finds a high level of unique protein associated with the class, supporting its delineation as a separate taxon

Post-transcriptional control during chronic inflammation and cancer: a focus on AU-rich elements

A considerable number of genes that code for AU-rich mRNAs including cytokines, growth factors, transcriptional factors, and certain receptors are involved in both chronic inflammation and cancer. Overexpression of these genes is affected by aberrations or by prolonged activation of several signaling pathways. AU-rich elements (ARE) are important cis-acting short sequences in the 3′UTR that mediate recognition of an array of RNA-binding proteins and affect mRNA stability and translation. This review addresses the cellular and molecular mechanisms that are common between inflammation and cancer and that also govern ARE-mediated post-transcriptional control. The first part examines the role of the ARE-genes in inflammation and cancer and sequence characteristics of AU-rich elements. The second part addresses the common signaling pathways in inflammation and cancer that regulate the ARE-mediated pathways and how their deregulations affect ARE-gene regulation and disease outcome

Tumor Necrosis Factor: from production to action

This article gives an overview of the mechanisms underlying TNF biosynthesis and its multiple biological activitie

Constitutive activity of the tumor necrosis factor promoter is canceled by the 3' untranslated region in nonmacrophage cell lines; a trans-dominant factor overcomes this suppressive effect.

The role of the mouse tumor necrosis factor (TNF) promoter, 5' untranslated region (UTR), and 3' UTR in TNF gene expression has been examined in three nonmacrophage cell lines (HeLa, NIH 3T3, and L-929). The TNF promoter is not macrophage-specific. On the contrary, it constitutively drives reporter gene expression in all three cell lines. Not only the full-length promoter but also truncated versions of the promoter, lacking NF-kappa B binding motifs, are active in each type of cell. The TNF 3' UTR effectively cancels reporter gene expression in HeLa cells and in NIH 3T3 cells but fails to block expression in L-929 cells. L-929 cells contain a factor that overcomes the inhibitory influence of the TNF 3' UTR. Its action depends upon the presence of sequences found in the TNF 5' UTR. Cell-fusion experiments reveal that this activator is trans-dominant. These studies highlight the essential role played by the TNF 3' UTR, which silences the TNF gene in cells that might otherwise express TNF. They also reveal the existence of an escape mechanism whereby inappropriate synthesis of TNF might occur