***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: Early detection of pulmonary hypertension ( PH ) in patients with systemic sclerosis ( SSc ) is essential as it leads to substantial morbidity and mortality irrespective of its etiology . The aim of our study was to determine whether noninvasive biochemical and /or echocardiographic indices can predict the presence of PH in these patients . We prospect ively studied 66 patients ( mean age of 57.7 ± 12.1 years , 63 women ) with SSc without clinical manifestations of heart failure . All patients underwent st and ard and tissue Doppler echocardiography .  Plasma N-terminal pro-B type natriuretic peptide ( NT-proBNP ) and asymmetric dimethylarginine ( ADMA ) levels were also measured . In 24 ( 36 % ) patients , the diagnosis of PH was established by echocardiography ( systolic pulmonary artery pressure value ≥40 mmHg ) . Left atrial ( LA ) volume , NT-proBNP , ADMA , ratio of early transmitral filling velocity to early diastolic velocity of the mitral annulus ( mitral E/Em ) , and right ventricular myocardial performance index ( MPI ) were univariate predictors of PH . In multivariate analysis , NT-proBNP , LA volume , and right ventricular MPI were independent predictors of PH in SSc patients . LA volume and NT-proBNP may be useful noninvasive markers for the prediction of elevated pulmonary artery pressure in patients with SSc . These parameters should be considered when assessing this population for risk stratification and for identification of patients dem and ing further investigation and institution of specific therapy for the disease at the time when it is most likely to be effective This pilot aims to better underst and the market for childcare in Saudi Arabia – both the supply and dem and sides – and to design a r and omized controlled experiment to test whether access to affordable day care ( in the form of subsidies , for example ) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired . In addition , the study seeks to underst and the degree to which employment early on in one ’s life impacts employment in later stages . The pilot will provide information on the groups of women the experiment should target , appropriate levels for the childcare subsidy , and the quality and current geographic locations of daycare sites . Expected Impact Determine the effects of facilitating childcare access on Saudi women ’s employment . PRINCIPAL INVESTIGATORS  Boston University Patricia Cortes  Harvard University Claudia Goldin  Swarthmore College Jennifer BACKGROUND  Asymmetric dimethylarginine ( ADMA ) is associated with endothelial injury . Increased ADMA levels are found in rheumatoid arthritis ( RA ) and ankylosing spondylitis ( AS ) . We set out to assess the  ADMA and symmetric dimethylarginine ( SDMA ) levels in AS , RA , and healthy controls , and in the anti-TNF treated patients with active AS . METHODS In 78AS patients and 29 RA patients who were anti-TNF treatment naive at baseline , along with 23 healthy control subjects , we assessed erythrocyte sedimentation rate ( ESR ) , high-sensitivity C-reactive protein ( hsCRP ) , ADMA , and SDMA . For AS patients , the Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) , back pain VAS and patient 's global activity of disease were calculated . After 6 months , we repeated the assessment in 30 out of the 78 AS patients in whom the anti-TNF treatment was initiated . RESULTS The baseline mean ( SD ) plasma ADMA concentration of AS patients was 0.64 ( 0.19 ) μmol/l and did not differ from controls ( 0.65 [ 0.19 ] μmol/l , p > 0.05 ) . In the RA group , ADMA concentration was higher than in controls ( 0.77 vs. 0.65 μmol/l , p < 0.05 ) . Both at baseline and at follow-up , ADMA levels correlated positively with BASDAI ( R = 0.52 , p = 0.02 , and R = 0.47 , p = 0.04 , baseline and follow-up , respectively ) . Six months of anti-TNF treatment did not influence ADMA concentration ( 0.51 [ 0.12 ] vs. 0.51 [ 0.11 ] μmol/l , p = 0.70 ) . CONCLUSION An absence of changes in plasma ADMA levels in the anti-TNF treated AS group despite the improvement in disease activity ( BASDAI ) and inflammation ( ESR , CRP ) may suggest either a lack of effect , or , even if such an effect were to take place , it needs not imply measurable changes in blood ADMA We explored the role of asymmetrical dimethylarginine ( ADMA ) as a cause of endothelial dysfunction induced by systemic inflammation . In vitro data suggest that ADMA bioavailability is regulated by proinflammatory stimuli , but it is unclear whether ADMA is a link between inflammation and endothelial dysfunction in humans . In study 1 we recruited 351 patients with coronary artery disease ( CAD ) and 87 healthy controls . In study 2 we recruited 69 CAD , 69 healthy , and 10 patients with rheumatoid arthritis , whereas in study 3 , 22 healthy and 70 CAD subjects were r and omly assigned to Salmonella typhii vaccination ( n=11 healthy and n=60 CAD ) or placebo ( n=11 healthy and n=10 CAD ) . Circulating interleukin 6/ADMA and flow-mediated dilation ( FMD ) were measured at 0 and 8 hours . In study 1 , ADMA was inversely correlated with FMD in healthy individuals and CAD patients ( P<0.0001 for both ) . However , interleukin 6 was inversely correlated with FMD ( P<0.0001 ) in healthy subjects but not in CAD patients . The positive correlation between ADMA and interleukin 6 was stronger in healthy ( r=0.515 ; P<0.0001 ) compared with CAD ( r=0.289 ; P=0.0001 ) subjects . In study 2 , both patients with rheumatoid arthritis and CAD had higher interleukin 6 ( P<0.0001 ) and ADMA ( P=0.004 ) but lower FMD ( P=0.001 ) versus healthy subjects . In study 3 , vaccination increased interleukin 6 in healthy ( P<0.001 ) and CAD ( P<0.001 ) subjects . FMD was reduced in healthy subjects ( P<0.05 ) , but its reduction in CAD was borderline . Vaccination increased ADMA only in healthy subjects ( P<0.001 ) . Systemic , low- grade inflammation leads to increased ADMA that may induce endothelial dysfunction . This study demonstrated that ADMA may be a link between inflammation and endothelial dysfunction in humans BACKGROUND  Asymmetric dimethylarginine ( ADMA ) is an endogenous competitive inhibitor of nitric oxide ( NO ) synthase . Because endothelial NO elaboration is impaired in hypercholesterolemia , we investigated whether plasma concentrations of ADMA are elevated in young , clinical ly asymptomatic hypercholesterolemic adults . We further studied whether such elevation of ADMA levels was correlated with impaired endothelium-dependent , NO-mediated vasodilation and urinary nitrate excretion . In a r and omized , double-blind , placebo-controlled study , we investigated whether these changes could be reversed with exogenous L-arginine . METHODS AND RESULTS We measured plasma levels of L-arginine , ADMA , and symmetrical dimethylarginine ( SDMA )  by high-performance liquid chromatography in 49 hypercholesterolemic ( HC ) and 31 normocholesterolemic ( NC ) humans . In 8 HC subjects , endothelium-dependent forearm vasodilation was assessed before and after an intravenous infusion of L-arginine or placebo and compared with 8 NC control subjects . ADMA levels were significantly elevated by > 100 % ( 2.17+/-0.15 versus 1.03+/-0.09 micromol/L ; P<0.05 ) in HC subjects compared with NC adults . L-Arginine levels were similar , result ing in a significantly decreased L-arginine/ADMA ratio in HC subjects ( 27.7+/-2.4 versus 55 . 7+/-5.4 ; P<0.05 ) . In 8 HC subjects , intravenous infusion of L-arginine significantly increased the L-arginine/ADMA ratio and normalized endothelium-dependent vasodilation and urinary nitrate excretion . ADMA levels were inversely correlated with endothelium-mediated vasodilation ( R=0.762 , P<0.01 ) and urinary nitrate excretion rates ( R=0.534 , P<0.01 ) . CONCLUSIONS We find that ADMA is elevated in young HC individuals . Elevation of ADMA is associated with impaired endothelium-dependent vasodilation and reduced urinary nitrate excretion . This abnormality is reversed by administration of L-arginine . ADMA may be a novel risk factor for endothelial dysfunction in humans Objectives . Impaired endothelial function represents the early stage of atherosclerosis , which is typically associated with systemic inflammatory diseases like rheumatoid arthritis ( RA ) . As modulators of endothelial nitric oxide synthase expression , asymmetric-dimethylarginine ( ADMA ) and apelin might be measured in the blood of RA patients to detect early atherosclerotic changes . We conducted a prospect i ve , case-control study to investigate serum ADMA and apelin profiles of patients with early-stage RA ( ERA ) before and after disease-modifying antirheumatic drug ( DMARD ) therapy . Methods . We enrolled 20 consecutively diagnosed , treatment-naïve patients with ERA and 20 matched healthy controls .  Serum ADMA and apelin levels and the 28-joint disease activity scores ( DAS28 ) were assessed before and after 12 months of DMARDs treatment . All patients underwent ultrasonographic assessment for intima-media tickness ( IMT ) evaluation . Results . In the ERA group , ADMA serum levels were significantly higher than controls at baseline ( P = 0.007 ) and significantly decreased after treatment ( P = 0.012 versus controls ) . Baseline serum apelin levels were significantly decreased in this group ( P = 0.0001 versus controls ) , but they were not significantly altered by treatment . IMT did not show significant changes . Conclusions . ERA is associated with alterations of serum ADMA and apelin levels , which might be used as biomarkers to detect early endothelial dysfunction in these patients Background Heart and pulmonary involvement is a leading cause of systemic sclerosis (SSc)-related deaths . Objectives The aim of our study was to assess if biochemical markers of right ventricular ( RV ) overload , endothelial function and collagen metabolism can predict RV dysfunction assessed by Doppler echocardiography in SSc patients . Methods We prospect ively studied 111 consecutive patients ( 101 F , 10 M , age 54.2 ± 13.8 years ) with diagnosed SSc ( mean disease duration 9.4 ± 11.4 years ) and a group of 21 age-matched subjects ( 18 F , 3 M , age 49.3 + 10.5 years ) . We performed transthoracic echocardiography ( Phillips iE 33 ) and measured serum endothelin-1 ( ET-1 ) , N-terminal pro-brain natriuretic peptide ( NT-proBNP ) , asymmetric dimethylarginine ( ADMA ) , endoglin and human tissue inhibitor of matrix metalloproteinase ( TIMP-1 ) concentration . Results Median serum NT-proBNP level in SSc patients was 133.5 ( range 21.86–17,670 pg/ml ) and was significantly higher than in controls ( p = 0.0002 ) . Moreover , the median serum ET-1 level of 1.49 ( range 0.26–8.75 pg/ml ) was higher in SSc patients ( p = 0.002 ) . However , no significant differences in ADMA , TIMP-1 and endoglin serum concentration between SSc patients and controls were observed . Serum NT-proBNP concentration correlated positively with echocardiographic signs of RV overload : tricuspid regurgitation pressure gradient ( r = 0.38 , p = 0.0004 ) and RV Tei index ( r = 0.25 , p = 0.01 ) . ET-1 serum level correlated negatively with tricuspid annular plane systolic excursion ( r = −0.4 , p = 0.01 ) and positively with inferior vena cava diameter measured at expiration ( r = 0.38 , p = 0.0002 ) . The echocardiographic signs of RV overload were significantly more pronounced in the highest NT-proBNP tertile ( > 195 pg/ml ) group than in the lowest one ( < 88 pg/ml ) . Conclusions Serum ET-1 and NT-proBNP , but not endoglin , ADMA and TIMP-1 levels correlating with the echocardiographic parameters of 
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Differences in ADMA concentrations between controls and RDs patients were not significantly associated with inflammatory markers , increasing age , lipid concentrations , body mass index , blood pressure , or methodology used to assess ADMA .
This meta- analysis showed that , in the context of significant between- study heterogeneity , circulating concentrations of ADMA  are positively related to RDs