***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Severe malaria remains a major cause of childhood mortality globally . Decreased endothelial nitric oxide is associated with severe and fatal malaria . The hypothesis was that adjunctive inhaled nitric oxide ( iNO ) would improve outcomes in African children with severe malaria . Methods A r and omized , blinded , placebo-controlled trial of iNO at 80 ppm by non-rebreather mask versus room air placebo as adjunctive treatment to artesunate in children with severe malaria was conducted . The primary outcome was the longitudinal course of angiopoietin-2 ( Ang-2 ) , an endothelial biomarker of malaria severity and clinical outcome . Results One hundred and eighty children were enrolled ; 88 were assigned to iNO and 92 to placebo ( all received IV artesunate ) . Ang-2 levels measured over the first 72 h of hospitalization were not significantly different between groups . The mortality at 48 h was similar between groups [ 6/87 ( 6.9 % ) in the iNO group vs 8/92 ( 8.7 % ) in the placebo group ; OR 0.78 , 95 % CI 0.26–2.3 ; p = 0.65 ] . Clinical recovery times and parasite clearance kinetics were similar ( p > 0.05 ) . Methaemoglobinaemia > 7 % occurred in 25 % of patients receiving iNO and resolved without sequelae . The incidence of neurologic deficits ( < 14 days ) , acute kidney injury , hypoglycaemia , anaemia , and haemoglobinuria was similar between groups ( p > 0.05 ) . Conclusions iNO at 80 ppm administered by non-rebreather mask was safe but did not affect circulating levels of Ang-2 . Alternative methods of enhancing endothelial NO bioavailability may be necessary to achieve a biological effect and improve clinical outcome .Trial Registration : Clinical Trials.gov Background Differentiating cerebral malaria ( CM ) from other causes of serious illness in African children is problematic , owing to the non-specific nature of the clinical presentation and the high prevalence of incidental parasitaemia . CM is associated with endothelial activation . In this study we tested the hypothesis that endothelium-derived biomarkers are associated with the pathophysiology of severe malaria and may help identify children with CM . Methods and Findings Plasma sample s were tested from children recruited with uncomplicated malaria ( UM ; n = 32 ) , cerebral malaria with retinopathy ( CM-R ; n = 38 ) , clinical ly defined CM without retinopathy ( CM-N ; n = 29 ) , or non-malaria febrile illness with decreased consciousness ( CNS ; n = 24 ) . Admission levels of  angiopoietin-2 ( Ang-2 ) , Ang-1 , soluble Tie-2 ( sTie-2  ) ,  von Willebr and factor  (  VWF  ) , its propeptide  ( VWFpp ) ,  vascular endothelial growth factor ( VEGF ) ,  soluble ICAM-1  ( sICAM-1 ) and  interferon-inducible protein 10 ( IP-10 ) were measured by ELISA . Children with CM-R had significantly higher median levels of Ang-2 , Ang-2:Ang-1 , sTie-2 , VWFpp and sICAM-1 compared to children with CM-N. Children with CM-R had significantly lower median levels of Ang-1 and higher median concentrations of Ang-2:Ang-1 , sTie-2 , VWF , VWFpp , VEGF and sICAM-1 compared to UM , and significantly lower median levels of Ang-1 and higher median levels of Ang-2 , Ang-2:Ang-1 , VWF and VWFpp compared to children with fever and altered consciousness due to other causes . Ang-1 was the best discriminator between UM and CM-R and between CNS and CM-R ( areas under the ROC curve of 0.96 and 0.93 , respectively ) . A comparison of biomarker levels in CM-R between admission and recovery showed uniform increases in Ang-1 levels , suggesting this biomarker may have utility in monitoring clinical response . Conclusions These results suggest that endothelial proteins are informative biomarkers of malarial disease severity . These results require validation in prospect i ve studies to confirm that this group of biomarkers improves the diagnostic accuracy of CM from similar conditions causing fever and altered consciousness Peripheral vascular disease ( PVD ) is an indicator of diffuse atherosclerosis and is associated with a greatly increased incidence of coronary heart and cerebrovascular disease . Although several studies have assessed whether in vivo platelet activation takes place in patients with PVD , no data are available comparing different platelet function tests in this patient population . We have compared prospect ively four tests for the measurement of in vivo platelet activation ( plasma betaTG , plasma PF4 , intraplatelet betaTG and urinary excretion of 11-dehydro-TXB2 ) and one in vitro platelet function test ( ADP-induced platelet aggregation ) in 63 well-characterized patients with intermittent claudication and in 18 age- and sex-matched healthy volunteers . No statistically significant difference was found between patients and controls for plasma betaTG ( 20.0 + /- 11.8 vs. 18.8 + /- 9.0 ng/ml , respectively ) , plasma PF4 ( 5.2 + /- 2.9 vs. 6.3 + /- 3.5 ng/ml ) , betaTG/PF4 ratio ( 4.0 + /- 2.9 vs. 3.6 + /- 1.8 ) , intraplatelet betaTG ( 4503 + /- 1482 vs. 4059 + /- 1065 ng/ml ) , and threshold aggregatory concentration of ADP ( 1.7 + /- 0.72 vs. 1.45 + /- 0.56 microM ) . Urinary 11-dehydro-TXB2 was instead significantly higher in the PVD group ( 55.4 + /- 27.5 vs. 26.7 + /- 7.0 ng/h , p < 0.001 ) . Our study shows that urinary 11-dehydro-TXB2 is a more sensitive index of in vivo platelet activation than the measurement of either platelet specific proteins or of in vitro platelet aggregation in patients with PVD Background For rapid initiation of anti-malarial treatment and prevention of complications , early diagnosis and risk stratification is important in patients with Plasmodium falciparum malaria . Routine laboratory values do not correlate well with disease severity . The aim of this study was to determine the diagnostic and prognostic value of several biomarkers related to inflammation ; endothelial and cardiac dysfunction ; coagulation , and haemolysis in imported P. falciparum malaria . Methods In a prospect i ve case-control study , 79 adult travellers with both uncomplicated and complicated P. falciparum malaria were included between 2007 and 2011 . Forty-one healthy subjects were included as controls . Blood sample s were obtained within 24 hours after first consultation to assess routine laboratory values as well as markers related to inflammation ( PAPP-A , copeptin , CRP ) , endothelial activation ( MPO , elastase-2 , endothelin-1 , sICAM-1 , sVCAM-1 ) , cardiac function ( NT-proBNP , MR-proANP ) , coagulation ( fibrinogen , D-dimers , platelet count ) , and haemolysis ( LDH ) . Prognostic performance was assessed using the receiver operating characteristic curve ( area under the curve = AUROC ) . Results Twelve ( 15.2 % ) patients had severe P. falciparum malaria . In the patient group , significant thrombocytopaenia was found , all other markers but PAPP-A were significantly elevated . Diagnostic performance was best for CRP with an AUROC of 1.00 , followed by MPO ( 0.99 ) , D-dimers ( 0.98 ) , elastase-2 ( 0.98 ) , and sICAM-1 ( 0.98 ) . Biomarker levels did not correlate well with disease severity . Conclusion The combination of travel history , fever prior to blood sampling , and CRP serum levels above or below 10.8 mg/l upon hospital admission , best discriminated between malaria patients and control persons . None of the biomarkers studied predicted the presence or the development of malaria complications , neither at the time of admission , nor during hospitalization 
    Output:
    
Prophylactic administration of FTY720 , rosiglitazone or inhalation of nitric oxide ( NO ) during malaria disease in mice result ed in an increase in Ang-1 , a decrease in Ang-2 and an increased survival .
For rosiglitazone , a decrease in Ang-2/Ang-1 ratio was observed after post-infection treatment in mice and humans with malaria , but for inhalation of NO , an effect on Ang-1 and survival was only observed in mice .
Conclusion Both Ang-1 and Ang-2 levels correlate with and can distinguish between malaria disease severity states within the group of malaria-infected patients .
Changes in levels of Ang-1 and Ang-2 might also reflect treatment effectiveness and are promising therapeutic targets as part of multi-targeted therapy