human
***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 & AIMS Liver biopsy analysis is the st and ard method used to diagnose nonalcoholic fatty liver disease ( NAFLD ) . Advanced magnetic resonance imaging is a noninvasive procedure that can accurately diagnose and quantify steatosis , but is expensive . Conventional ultrasound is more accessible but identifies steatosis with low levels of sensitivity , specificity , and quantitative accuracy , and results vary among technicians . A new quantitative ultrasound ( QUS ) technique can identify steatosis in animal models . We assessed the accuracy of QUS in the diagnosis and quantification of hepatic steatosis , comparing findings with those from magnetic resonance imaging proton density fat fraction ( MRI-PDFF ) analysis as a reference . METHODS We performed a prospect i ve , cross-sectional analysis of a cohort of adults ( N = 204 ) with NAFLD ( MRI-PDFF , ≥5 % ) and without NAFLD ( controls ) . Subjects underwent MRI-PDFF and QUS analyses of the liver on the same day at the University of California , San Diego , from February 2012 through March 2014 . QUS parameters and backscatter coefficient ( BSC ) values were calculated . Patients were assigned r and omly to training ( n = 102 ; mean age , 51 ± 17 y ; mean body mass index , 31 ± 7 kg/m(2 ) ) and validation ( n = 102 ; mean age , 49 ± 17 y ; body mass index , 30 ± 6 kg/m(2 ) ) groups ; 69 % of patients in each group had NAFLD . RESULTS BSC ( range , 0.00005 - 0.25 1/cm-sr ) correlated with MRI-PDFF ( Spearman ρ = 0.80 ; P < .0001 ) . In the training group , the BSC analysis identified patients with NAFLD with an area under the curve value of 0.98 ( 95 % confidence interval , 0.95 - 1.00 ; P < .0001 ) . The optimal BSC cut-off value identified patients with NAFLD in the training and validation groups with 93 % and 87 % sensitivity , 97 % and 91 % specificity , 86 % and 76 % negative predictive values , and 99 % and 95 % positive predictive values , respectively . CONCLUSIONS QUS measurements of BSC can accurately diagnose and quantify hepatic steatosis , based on a cross-sectional analysis that used MRI-PDFF as the reference . With further validation , QUS could be an inexpensive , widely available method to screen the general or at-risk population for NAFLD Introduction : The purpose of this study was to investigate the effects of 12-week exercise training on circulating retinol-binding protein 4 ( RBP4 ) concentration and cardiovascular disease ( CVD ) risk factors in obese men . Methods : 29 obese men ( age 48 ± 2 years ; BMI 29.6 ± 0.7 kg/m2 ) participated in a 12-week exercise program ( 50–70 % maximal heart rates ; 3 times/week ) without calorie restriction . Anthropometric parameters , CVD risk factors ( total cholesterol , high-density lipoprotein cholesterol ( HDLC ) , low-density lipoprotein cholesterol , triglycerides ( TG ) , and quantitative insulin sensitivity check index ) , and circulating RBP4 and adipokine ( adiponectin , leptin , and interleukin-6 ( IL-6 ) ) concentrations were measured . Results : Exercise training significantly improved in absolute peak oxygen consumption ( p < 0.05 ) , and CVD risk factors ( p < 0.05 ) , with the exception of HDLC . There was a significant decrease in circulating RBP4 , leptin , and IL-6 concentrations ( p < 0.05 ) . Stepwise regression analysis revealed that changes in RBP4 concentration were independently related to the changes in TG concentration ( β = 0.46 , p < 0.05 ) . Conclusion : These results demonstrate that exercise training without calorie restriction improves several CVD risk factors and circulating RBP4 and adipokine concentrations . Moreover , the change in circulating RBP4 may be more associated with the improvements in TG concentration in obese men OBJECTIVE The purpose of this study is to explore the diagnostic performance of two investigational quantitative ultrasound ( QUS ) parameters , attenuation coefficient and backscatter coefficient , in comparison with conventional ultrasound ( CUS ) and MRI-estimated proton density fat fraction ( PDFF ) for predicting histology-confirmed steatosis grade in adults with nonalcoholic fatty liver disease ( NAFLD ) . SUBJECTS AND METHODS In this prospect ively design ed pilot study , 61 adults with histology-confirmed NAFLD were enrolled from September 2012 to February 2014 . Subjects underwent QUS , CUS , and MRI examinations within 100 days of clinical -care liver biopsy .  QUS parameters ( attenuation coefficient and backscatter coefficient ) were estimated using a reference phantom technique by two analysts independently . Three-point ordinal CUS scores intended to predict steatosis grade ( 1 , 2 , or 3 ) were generated independently by two radiologists on the basis of QUS features . PDFF was estimated using an advanced chemical shift-based MRI technique . Using histologic examination as the reference st and ard , ROC analysis was performed . Optimal attenuation coefficient , backscatter coefficient , and PDFF cutoff thresholds were identified , and the accuracy of attenuation coefficient , backscatter coefficient , PDFF , and CUS to predict steatosis grade was determined . Interobserver agreement for attenuation coefficient , backscatter coefficient , and CUS was analyzed . RESULTS CUS had 51.7 % grading accuracy . The raw and cross-vali date d steatosis grading accuracies were 61.7 % and 55.0 % , respectively , for attenuation coefficient , 68.3 % and 68.3 % for backscatter coefficient , and 76.7 % and 71.3 % for MRI-estimated PDFF . Interobserver agreements were 53.3 % for CUS ( κ = 0.61 ) , 90.0 % for attenuation coefficient ( κ = 0.87 ) , and 71.7 % for backscatter coefficient ( κ = 0.82 ) ( p < 0.0001 for all ) . CONCLUSION Preliminary observations suggest that QUS parameters may be more accurate and provide higher interobserver agreement than CUS for predicting hepatic steatosis grade in patients with NAFLD CONTEXT Retinol binding protein ( RBP4 ) , secreted primarily from the liver and adipose tissues , was recently proposed as a link between obesity and insulin resistance . The role of RBP4 in pediatric obesity , its relationship with sub clinical inflammation , and its response to lifestyle changes are not eluci date d. OBJECTIVE The objective of the study was to determine in children : 1 ) the status of RBP4 levels in lean vs. obese ; 2 ) the relationship between RBP4 levels and sub clinical inflammation ; and 3 ) the effect of lifestyle-only intervention on RBP4 levels . DESIGN , SETTING , AND PATIENTS Lean and obese children ( n = 21 ) matched for age ( > 14 yr to < 18 yr ) and maturity stage ( Tanner IV ) were studied at baseline and with lifestyle intervention in obese subjects only ( n = 15 ) . INTERVENTION Patients received 3 months of r and omized and controlled physical activity-based lifestyle intervention . MAIN OUTCOME MEASURE  RBP4 levels in children before and after intervention and the relationship between RBP4 and sub clinical inflammation were measured . RESULTS Higher RBP4 levels were found in the obese group vs. lean group ( P = 0.005 ) . RBP4 correlated with not only indices of obesity and insulin resistance but also inflammatory factors ( r = 0.63 and 0.64 for C-reactive protein and IL-6 , respectively , P < 0.01 ) . Intervention reduced RBP4 levels by approximately 30 % ( P = 0.001 ) , and RBP4 reduction was correlated with the magnitude of decrease in inflammatory factors ( P = 0.01 ) . CONCLUSION Alterations in serum RBP4 occur at an early age in the clinical course of obesity and appear to correlate with sub clinical inflammation . Lifestyle intervention almost entirely reversed the raised RBP4 levels in obese children . Future studies should determine whether elevation of RBP4 is a direct trigger for the insulin resistance and sub clinical inflammation implicated in the premature development of cardiovascular disease and diabetes Thiazolidinediones ( TZD ) may improve insulin resistance in patients with diabetes and HIV . The novel adipocytokines visfatin and retinol‐binding protein‐4 ( RBP‐4 ) have been proposed to influence the development of impaired glucose tolerance . The impact of TZD on these cytokines is yet unknown . In this r and omized , double‐blind , placebo‐controlled parallel group study , 37 lean HIV‐positive subjects aged 19–50 years were treated with 8 mg/day rosiglitazone ( n=20 ) or placebo ( n=17 ) for 6 months . Insulin sensitivity was estimated from the homeostasis model assessment ( HOMA ) index . Fasting visfatin , RBP‐4 , leptin , and adiponectin plasma concentrations were analyzed by immunoassays . Rosiglitazone had no effect on impaired insulin sensitivity , but increased median plasma visfatin from 6.2 ng/ml ( 95 % CI : 5.9 ; 6.5 ) to 13.7 ng/ml ( 12.6 ; 19.1 ) ( P<0.001 ) and adiponectin from 3.2 ng/ml ( 2.2 ; 4.0 ) to 4.0 ng/ml ( 3.3 ; 8.5 ; P<0.001 ) . RBP‐4 was lowered from 21.0 ng/ml ( 19.6 ; 23.1 ) to 16.3 ng/ml ( 15.2 ; 17.0 ; P<0.001 ) , and leptin concentrations were unchanged . Adipocytokine concentrations were stable in subjects receiving placebo , where a deterioration in insulin sensitivity was detectable ( P<0.05 ) . Changes in visfatin and RBP‐4 were correlated in subjects receiving rosiglitazone ( r=−0.64 , P<0.01 ) but not placebo ( r=0.12 , P=0.15 ) . TZD treatment affects circulating adipocytokine concentrations in subjects with HIV .  Reductions in RBP‐4 and increases in visfatin may contribute to the pharmacodynamic action of TZD on glucose homeostasis . Quantification of adipocytokines might be useful to assess TZD treatment effectiveness in insulin‐resistant subjects with HIV CONTEXT Administration of retinol-binding protein 4 ( RBP-4 ) impairs insulin sensitivity in animals , and elevated serum concentrations have been associated with insulin resistance in humans . OBJECTIVE We have studied whether weight loss influences RBP-4 . PATIENTS AND METHODS Fasting serum concentrations of RBP-4  were measured before and 6 months after gastric b and ing surgery in 33 morbidly obese patients aged 40 + /- 11 yr with a body mass index ( BMI ) of 46 + /- 5 kg/m(2 ) . Fourteen healthy subjects aged 29 + /- 5 yr with a BMI less than 25 kg/m(2 ) served as controls . To characterize the association of weight loss with central and peripheral appetite regulation , the signaling protein agouti-related protein ( AGRP ) , the orexigenic hormone ghrelin , and its recently identified antagonist obestatin were determined . RESULTS At baseline , RBP-4 levels were markedly higher in obese than in lean subjects ( 2.7 + /- 0.5 vs. 0.9 + /- 0.5 microg/ml ; P < 0.001 ) . In contrast , AGRP and obestatin were lower in obese subjects compared with lean controls ( all P < 0.001 ) . Six months after gastric b and ing , BMI was reduced to 40 + /- 5 kg/m(2 ) , RBP-4 was reduced to 2.0 + /- 0.7 microg/ml , AGRP increased from 1.8 + /- 1.1 to 3.4 + /- 1.1 ng/ml , ghrelin increased from 93 + /- 58 to 131 + /- 70 pg/ml , and obestatin increased from 131 + /- 52 to 173 + /- 35 pg/ml ( all P < 0.05 ) . Individual changes of RBP-4 were associated with changes of BMI ( r = 0.72 ) , the homeostasis model assessment insulin resistance-index ( r = 0.53 ) , and total cholesterol ( r = 0.42 , for all P < 0.05 ) . CONCLUSION Reductions in circulating RBP-4 may contribute to improved insulin resistance in morbidly obese subjects after weight loss . This is accompanied by favorable changes in appetite-regulating hormones , which might support the sustained weight loss after ob 
    Output:
    
agent
***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 & AIMS Liver biopsy analysis is the st and ard method used to diagnose nonalcoholic fatty liver disease ( NAFLD ) . Advanced magnetic resonance imaging is a noninvasive procedure that can accurately diagnose and quantify steatosis , but is expensive . Conventional ultrasound is more accessible but identifies steatosis with low levels of sensitivity , specificity , and quantitative accuracy , and results vary among technicians . A new quantitative ultrasound ( QUS ) technique can identify steatosis in animal models . We assessed the accuracy of QUS in the diagnosis and quantification of hepatic steatosis , comparing findings with those from magnetic resonance imaging proton density fat fraction ( MRI-PDFF ) analysis as a reference . METHODS We performed a prospect i ve , cross-sectional analysis of a cohort of adults ( N = 204 ) with NAFLD ( MRI-PDFF , ≥5 % ) and without NAFLD ( controls ) . Subjects underwent MRI-PDFF and QUS analyses of the liver on the same day at the University of California , San Diego , from February 2012 through March 2014 . QUS parameters and backscatter coefficient ( BSC ) values were calculated . Patients were assigned r and omly to training ( n = 102 ; mean age , 51 ± 17 y ; mean body mass index , 31 ± 7 kg/m(2 ) ) and validation ( n = 102 ; mean age , 49 ± 17 y ; body mass index , 30 ± 6 kg/m(2 ) ) groups ; 69 % of patients in each group had NAFLD . RESULTS BSC ( range , 0.00005 - 0.25 1/cm-sr ) correlated with MRI-PDFF ( Spearman ρ = 0.80 ; P < .0001 ) . In the training group , the BSC analysis identified patients with NAFLD with an area under the curve value of 0.98 ( 95 % confidence interval , 0.95 - 1.00 ; P < .0001 ) . The optimal BSC cut-off value identified patients with NAFLD in the training and validation groups with 93 % and 87 % sensitivity , 97 % and 91 % specificity , 86 % and 76 % negative predictive values , and 99 % and 95 % positive predictive values , respectively . CONCLUSIONS QUS measurements of BSC can accurately diagnose and quantify hepatic steatosis , based on a cross-sectional analysis that used MRI-PDFF as the reference . With further validation , QUS could be an inexpensive , widely available method to screen the general or at-risk population for NAFLD Introduction : The purpose of this study was to investigate the effects of 12-week exercise training on circulating retinol-binding protein 4 ( RBP4 ) concentration and cardiovascular disease ( CVD ) risk factors in obese men . Methods : 29 obese men ( age 48 ± 2 years ; BMI 29.6 ± 0.7 kg/m2 ) participated in a 12-week exercise program ( 50–70 % maximal heart rates ; 3 times/week ) without calorie restriction . Anthropometric parameters , CVD risk factors ( total cholesterol , high-density lipoprotein cholesterol ( HDLC ) , low-density lipoprotein cholesterol , triglycerides ( TG ) , and quantitative insulin sensitivity check index ) , and circulating RBP4 and adipokine ( adiponectin , leptin , and interleukin-6 ( IL-6 ) ) concentrations were measured . Results : Exercise training significantly improved in absolute peak oxygen consumption ( p < 0.05 ) , and CVD risk factors ( p < 0.05 ) , with the exception of HDLC . There was a significant decrease in circulating RBP4 , leptin , and IL-6 concentrations ( p < 0.05 ) . Stepwise regression analysis revealed that changes in RBP4 concentration were independently related to the changes in TG concentration ( β = 0.46 , p < 0.05 ) . Conclusion : These results demonstrate that exercise training without calorie restriction improves several CVD risk factors and circulating RBP4 and adipokine concentrations . Moreover , the change in circulating RBP4 may be more associated with the improvements in TG concentration in obese men OBJECTIVE The purpose of this study is to explore the diagnostic performance of two investigational quantitative ultrasound ( QUS ) parameters , attenuation coefficient and backscatter coefficient , in comparison with conventional ultrasound ( CUS ) and MRI-estimated proton density fat fraction ( PDFF ) for predicting histology-confirmed steatosis grade in adults with nonalcoholic fatty liver disease ( NAFLD ) . SUBJECTS AND METHODS In this prospect ively design ed pilot study , 61 adults with histology-confirmed NAFLD were enrolled from September 2012 to February 2014 . Subjects underwent QUS , CUS , and MRI examinations within 100 days of clinical -care liver biopsy .  QUS parameters ( attenuation coefficient and backscatter coefficient ) were estimated using a reference phantom technique by two analysts independently . Three-point ordinal CUS scores intended to predict steatosis grade ( 1 , 2 , or 3 ) were generated independently by two radiologists on the basis of QUS features . PDFF was estimated using an advanced chemical shift-based MRI technique . Using histologic examination as the reference st and ard , ROC analysis was performed . Optimal attenuation coefficient , backscatter coefficient , and PDFF cutoff thresholds were identified , and the accuracy of attenuation coefficient , backscatter coefficient , PDFF , and CUS to predict steatosis grade was determined . Interobserver agreement for attenuation coefficient , backscatter coefficient , and CUS was analyzed . RESULTS CUS had 51.7 % grading accuracy . The raw and cross-vali date d steatosis grading accuracies were 61.7 % and 55.0 % , respectively , for attenuation coefficient , 68.3 % and 68.3 % for backscatter coefficient , and 76.7 % and 71.3 % for MRI-estimated PDFF . Interobserver agreements were 53.3 % for CUS ( κ = 0.61 ) , 90.0 % for attenuation coefficient ( κ = 0.87 ) , and 71.7 % for backscatter coefficient ( κ = 0.82 ) ( p < 0.0001 for all ) . CONCLUSION Preliminary observations suggest that QUS parameters may be more accurate and provide higher interobserver agreement than CUS for predicting hepatic steatosis grade in patients with NAFLD CONTEXT Retinol binding protein ( RBP4 ) , secreted primarily from the liver and adipose tissues , was recently proposed as a link between obesity and insulin resistance . The role of RBP4 in pediatric obesity , its relationship with sub clinical inflammation , and its response to lifestyle changes are not eluci date d. OBJECTIVE The objective of the study was to determine in children : 1 ) the status of RBP4 levels in lean vs. obese ; 2 ) the relationship between RBP4 levels and sub clinical inflammation ; and 3 ) the effect of lifestyle-only intervention on RBP4 levels . DESIGN , SETTING , AND PATIENTS Lean and obese children ( n = 21 ) matched for age ( > 14 yr to < 18 yr ) and maturity stage ( Tanner IV ) were studied at baseline and with lifestyle intervention in obese subjects only ( n = 15 ) . INTERVENTION Patients received 3 months of r and omized and controlled physical activity-based lifestyle intervention . MAIN OUTCOME MEASURE  RBP4 levels in children before and after intervention and the relationship between RBP4 and sub clinical inflammation were measured . RESULTS Higher RBP4 levels were found in the obese group vs. lean group ( P = 0.005 ) . RBP4 correlated with not only indices of obesity and insulin resistance but also inflammatory factors ( r = 0.63 and 0.64 for C-reactive protein and IL-6 , respectively , P < 0.01 ) . Intervention reduced RBP4 levels by approximately 30 % ( P = 0.001 ) , and RBP4 reduction was correlated with the magnitude of decrease in inflammatory factors ( P = 0.01 ) . CONCLUSION Alterations in serum RBP4 occur at an early age in the clinical course of obesity and appear to correlate with sub clinical inflammation . Lifestyle intervention almost entirely reversed the raised RBP4 levels in obese children . Future studies should determine whether elevation of RBP4 is a direct trigger for the insulin resistance and sub clinical inflammation implicated in the premature development of cardiovascular disease and diabetes Thiazolidinediones ( TZD ) may improve insulin resistance in patients with diabetes and HIV . The novel adipocytokines visfatin and retinol‐binding protein‐4 ( RBP‐4 ) have been proposed to influence the development of impaired glucose tolerance . The impact of TZD on these cytokines is yet unknown . In this r and omized , double‐blind , placebo‐controlled parallel group study , 37 lean HIV‐positive subjects aged 19–50 years were treated with 8 mg/day rosiglitazone ( n=20 ) or placebo ( n=17 ) for 6 months . Insulin sensitivity was estimated from the homeostasis model assessment ( HOMA ) index . Fasting visfatin , RBP‐4 , leptin , and adiponectin plasma concentrations were analyzed by immunoassays . Rosiglitazone had no effect on impaired insulin sensitivity , but increased median plasma visfatin from 6.2 ng/ml ( 95 % CI : 5.9 ; 6.5 ) to 13.7 ng/ml ( 12.6 ; 19.1 ) ( P<0.001 ) and adiponectin from 3.2 ng/ml ( 2.2 ; 4.0 ) to 4.0 ng/ml ( 3.3 ; 8.5 ; P<0.001 ) . RBP‐4 was lowered from 21.0 ng/ml ( 19.6 ; 23.1 ) to 16.3 ng/ml ( 15.2 ; 17.0 ; P<0.001 ) , and leptin concentrations were unchanged . Adipocytokine concentrations were stable in subjects receiving placebo , where a deterioration in insulin sensitivity was detectable ( P<0.05 ) . Changes in visfatin and RBP‐4 were correlated in subjects receiving rosiglitazone ( r=−0.64 , P<0.01 ) but not placebo ( r=0.12 , P=0.15 ) . TZD treatment affects circulating adipocytokine concentrations in subjects with HIV .  Reductions in RBP‐4 and increases in visfatin may contribute to the pharmacodynamic action of TZD on glucose homeostasis . Quantification of adipocytokines might be useful to assess TZD treatment effectiveness in insulin‐resistant subjects with HIV CONTEXT Administration of retinol-binding protein 4 ( RBP-4 ) impairs insulin sensitivity in animals , and elevated serum concentrations have been associated with insulin resistance in humans . OBJECTIVE We have studied whether weight loss influences RBP-4 . PATIENTS AND METHODS Fasting serum concentrations of RBP-4  were measured before and 6 months after gastric b and ing surgery in 33 morbidly obese patients aged 40 + /- 11 yr with a body mass index ( BMI ) of 46 + /- 5 kg/m(2 ) . Fourteen healthy subjects aged 29 + /- 5 yr with a BMI less than 25 kg/m(2 ) served as controls . To characterize the association of weight loss with central and peripheral appetite regulation , the signaling protein agouti-related protein ( AGRP ) , the orexigenic hormone ghrelin , and its recently identified antagonist obestatin were determined . RESULTS At baseline , RBP-4 levels were markedly higher in obese than in lean subjects ( 2.7 + /- 0.5 vs. 0.9 + /- 0.5 microg/ml ; P < 0.001 ) . In contrast , AGRP and obestatin were lower in obese subjects compared with lean controls ( all P < 0.001 ) . Six months after gastric b and ing , BMI was reduced to 40 + /- 5 kg/m(2 ) , RBP-4 was reduced to 2.0 + /- 0.7 microg/ml , AGRP increased from 1.8 + /- 1.1 to 3.4 + /- 1.1 ng/ml , ghrelin increased from 93 + /- 58 to 131 + /- 70 pg/ml , and obestatin increased from 131 + /- 52 to 173 + /- 35 pg/ml ( all P < 0.05 ) . Individual changes of RBP-4 were associated with changes of BMI ( r = 0.72 ) , the homeostasis model assessment insulin resistance-index ( r = 0.53 ) , and total cholesterol ( r = 0.42 , for all P < 0.05 ) . CONCLUSION Reductions in circulating RBP-4 may contribute to improved insulin resistance in morbidly obese subjects after weight loss . This is accompanied by favorable changes in appetite-regulating hormones , which might support the sustained weight loss after ob 
    Output:
    