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Impaired Systemic Tetrahydrobiopterin Bioavailability and Increased Oxidized Biopterins in Pediatric Falciparum Malaria: Association with Disease Severity

Overview of attention for article published in PLoS Pathogens, March 2015
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (90th percentile)
  • High Attention Score compared to outputs of the same age and source (84th percentile)

Mentioned by

news
1 news outlet
twitter
12 tweeters
reddit
1 Redditor

Citations

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26 Dimensions

Readers on

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29 Mendeley
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Title
Impaired Systemic Tetrahydrobiopterin Bioavailability and Increased Oxidized Biopterins in Pediatric Falciparum Malaria: Association with Disease Severity
Published in
PLoS Pathogens, March 2015
DOI 10.1371/journal.ppat.1004655
Pubmed ID
Authors

Matthew P. Rubach, Jackson Mukemba, Salvatore Florence, Bert K. Lopansri, Keith Hyland, Alicia D. Volkheimer, Tsin W. Yeo, Nicholas M. Anstey, J. Brice Weinberg, Esther D. Mwaikambo, Donald L. Granger

Abstract

Decreased bioavailability of nitric oxide (NO) is a major contributor to the pathophysiology of severe falciparum malaria. Tetrahydrobiopterin (BH4) is an enzyme cofactor required for NO synthesis from L-arginine. We hypothesized that systemic levels of BH4 would be decreased in children with cerebral malaria, contributing to low NO bioavailability. In an observational study in Tanzania, we measured urine levels of biopterin in its various redox states (fully reduced [BH4] and the oxidized metabolites, dihydrobiopterin [BH2] and biopterin [B0]) in children with uncomplicated malaria (UM, n = 55), cerebral malaria (CM, n = 45), non-malaria central nervous system conditions (NMC, n = 48), and in 111 healthy controls (HC). Median urine BH4 concentration in CM (1.10 [IQR:0.55-2.18] μmol/mmol creatinine) was significantly lower compared to each of the other three groups - UM (2.10 [IQR:1.32-3.14];p<0.001), NMC (1.52 [IQR:1.01-2.71];p = 0.002), and HC (1.60 [IQR:1.15-2.23];p = 0.005). Oxidized biopterins were increased, and the BH4:BH2 ratio markedly decreased in CM. In a multivariate logistic regression model, each Log10-unit decrease in urine BH4 was independently associated with a 3.85-fold (95% CI:1.89-7.61) increase in odds of CM (p<0.001). Low systemic BH4 levels and increased oxidized biopterins contribute to the low NO bioavailability observed in CM. Adjunctive therapy to regenerate BH4 may have a role in improving NO bioavailability and microvascular perfusion in severe falciparum malaria.

Twitter Demographics

The data shown below were collected from the profiles of 12 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 29 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 29 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 7 24%
Student > Ph. D. Student 5 17%
Student > Bachelor 4 14%
Researcher 3 10%
Professor 3 10%
Other 4 14%
Unknown 3 10%
Readers by discipline Count As %
Medicine and Dentistry 12 41%
Agricultural and Biological Sciences 4 14%
Nursing and Health Professions 3 10%
Biochemistry, Genetics and Molecular Biology 2 7%
Computer Science 1 3%
Other 3 10%
Unknown 4 14%

Attention Score in Context

This research output has an Altmetric Attention Score of 16. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 May 2015.
All research outputs
#801,751
of 12,091,691 outputs
Outputs from PLoS Pathogens
#1,160
of 5,786 outputs
Outputs of similar age
#21,678
of 222,606 outputs
Outputs of similar age from PLoS Pathogens
#32
of 201 outputs
Altmetric has tracked 12,091,691 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 93rd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,786 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.7. This one has done well, scoring higher than 79% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 222,606 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 90% of its contemporaries.
We're also able to compare this research output to 201 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 84% of its contemporaries.