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Impaired Systemic Tetrahydrobiopterin Bioavailability and Increased Dihydrobiopterin in Adult Falciparum Malaria: Association with Disease Severity, Impaired Microvascular Function and Increased…

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 (84th percentile)
  • Good Attention Score compared to outputs of the same age and source (73rd percentile)

Mentioned by

news
1 news outlet
twitter
1 tweeter
reddit
1 Redditor

Citations

dimensions_citation
17 Dimensions

Readers on

mendeley
27 Mendeley
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Title
Impaired Systemic Tetrahydrobiopterin Bioavailability and Increased Dihydrobiopterin in Adult Falciparum Malaria: Association with Disease Severity, Impaired Microvascular Function and Increased Endothelial Activation.
Published in
PLoS Pathogens, March 2015
DOI 10.1371/journal.ppat.1004667
Pubmed ID
Authors

Tsin W. Yeo, Daniel A. Lampah, Enny Kenangalem, Emiliana Tjitra, Ric N. Price, J. Brice Weinberg, Keith Hyland, Donald L. Granger, Nicholas M. Anstey, Yeo TW, Lampah DA, Kenangalem E, Tjitra E, Price RN, Weinberg JB, Hyland K, Granger DL, Anstey NM, Kami Kim

Abstract

Tetrahydrobiopterin (BH4) is a co-factor required for catalytic activity of nitric oxide synthase (NOS) and amino acid-monooxygenases, including phenylalanine hydroxylase. BH4 is unstable: during oxidative stress it is non-enzymatically oxidized to dihydrobiopterin (BH2), which inhibits NOS. Depending on BH4 availability, NOS oscillates between NO synthase and NADPH oxidase: as the BH4/BH2 ratio decreases, NO production falls and is replaced by superoxide. In African children and Asian adults with severe malaria, NO bioavailability decreases and plasma phenylalanine increases, together suggesting possible BH4 deficiency. The primary three biopterin metabolites (BH4, BH2 and B0 [biopterin]) and their association with disease severity have not been assessed in falciparum malaria. We measured pterin metabolites in urine of adults with severe falciparum malaria (SM; n=12), moderately-severe malaria (MSM, n=17), severe sepsis (SS; n=5) and healthy subjects (HC; n=20) as controls. In SM, urinary BH4 was decreased (median 0.16 ¼mol/mmol creatinine) compared to MSM (median 0.27), SS (median 0.54), and HC (median 0.34)]; p<0.001. Conversely, BH2 was increased in SM (median 0.91 ¼mol/mmol creatinine), compared to MSM (median 0.67), SS (median 0.39), and HC (median 0.52); p<0.001, suggesting increased oxidative stress and insufficient recycling of BH2 back to BH4 in severe malaria. Overall, the median BH4/BH2 ratio was lowest in SM [0.18 (IQR: 0.04-0.32)] compared to MSM (0.45, IQR 0.27-61), SS (1.03; IQR 0.54-2.38) and controls (0.66; IQR 0.43-1.07); p<0.001. In malaria, a lower BH4/BH2 ratio correlated with decreased microvascular reactivity (r=0.41; p=0.03) and increased ICAM-1 (r=-0.52; p=0.005). Decreased BH4 and increased BH2 in severe malaria (but not in severe sepsis) uncouples NOS, leading to impaired NO bioavailability and potentially increased oxidative stress. 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 profile of 1 tweeter 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 27 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Germany 1 4%
Canada 1 4%
Unknown 25 93%

Demographic breakdown

Readers by professional status Count As %
Student > Master 5 19%
Researcher 4 15%
Student > Ph. D. Student 4 15%
Unspecified 3 11%
Lecturer 3 11%
Other 8 30%
Readers by discipline Count As %
Medicine and Dentistry 13 48%
Biochemistry, Genetics and Molecular Biology 3 11%
Unspecified 3 11%
Agricultural and Biological Sciences 2 7%
Social Sciences 2 7%
Other 4 15%

Attention Score in Context

This research output has an Altmetric Attention Score of 10. 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 27 January 2016.
All research outputs
#1,108,700
of 9,726,598 outputs
Outputs from PLoS Pathogens
#1,616
of 5,395 outputs
Outputs of similar age
#32,547
of 208,625 outputs
Outputs of similar age from PLoS Pathogens
#54
of 201 outputs
Altmetric has tracked 9,726,598 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,395 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.3. This one has gotten more attention than average, scoring higher than 69% 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 208,625 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 84% 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 gotten more attention than average, scoring higher than 73% of its contemporaries.