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 Heart and coronary calcifications in hemodialysis patients are of very common occurrence and linked to cardiovascular events and mortality . Several studies have been published with similar results . Most of them were mainly cross-sectional and some of the prospect i ve protocol s were aim ed to evaluate the results of the control of altered biochemical parameters of mineral disturbances with special regard to serum calcium , phosphate and CaxP with the use of calcium containing and calcium free phosphate chelating agents . The aim of the present study was to evaluate in hemodialysis patients classic and some non classic risk factors as predictors of calcification changes after one year and to evaluate the impact of progression on survival . Methods 81 patients on hemodialysis were studied , with a wide age range and HD vintage . Several classic parameters and some less classic risk factors were studied like fetuin-A , CRP , 25-OHD and leptin . Calcifications , as Agatston scores , were evaluated with Multislice CT basally and after 12 - 18 months . Results Coronary artery calcifications were observed in 71 of 81 patients . Non parametric correlations between Agatston scores and Age , HD Age , PTH and CRP were significant . Delta increments of Agatston scores correlated also with serum calcium , CaxP , Fetuin-A , triglycerides and serum albumin . Logistic regression analysis showed Age , PTH and serum calcium as important predictors of Delta Agatston scores . LN transformation of the not normally distributed variables restricted the significant correlations to Age , BMI and CRP . Considering the Delta Agatston scores as dependent , significant predictors were Age , PTH and HDL . A strong association was found between basal calcification scores and Delta increment at one year . By logistic analysis , the one year increments in Agatston scores were found to be predictors of mortality .  Diabetic and hypertensive patients have significantly higher Delta scores . Conclusions Progression of calcification is of common occurrence , with special regard to elevated basal scores , and is predictive of survival . Higher predictive value of survival is linked to the one year increment of calcification scores . Some classic and non classic risk factors play an important role in progression . Some of them could be controlled with appropriate management with possible improvement of mortality Background It is undetermined whether calcium supplementation has an effect on obesity or body composition in postmenopausal women . The purpose of the study is to detect the effect of calcium supplementation on indices of obesity and body composition . Methods This is a secondary analysis of data from a population -based , double-blind , placebo-controlled , r and omized trial design ed to determine the effects of calcium and vitamin D on osteoporotic fractures . The cohort included 1179 postmenopausal women who were r and omly assigned into one of three groups : 1 ) supplemental calcium ( 1400 mg/d or 1500 mg/d ) plus vitamin D placebo ( Ca-only group ) ; 2 ) supplemental calcium ( 1400 mg/d or 1500 mg/d ) plus supplemental vitamin D3 ( 1100 IU/d ) ( Ca + D group ) ; or , 3 ) two placebos ( placebo group ) . After applying the exclusion criteria for this analysis , 870 subjects were included in this study . The primary outcomes for the present study were changes in body mass index , trunk fat , trunk lean , and percentage of trunk fat after calcium supplementation . Results Changes in trunk fat , trunk lean , and percentage of trunk fat were significantly different between the calcium intervention groups ( Ca-only group or Ca + D group ) and the placebo group during the trial ( P < 0.05 ) . The calcium intervention groups gained less trunk fat and maintained more trunk lean when compared to the placebo group . No significant difference was observed for body mass index between groups . Conclusion Calcium supplementation over four years has a beneficial effect on body composition in postmenopausal women OBJECTIVE The aim of this study was to explore the effects of cholecalciferol supplementation on vitamin D levels , bone mineral density ( BMD ) , body fat distribution and insulin sensitivity in vitamin D-deficient HIV-1-infected patients . METHODS Twenty vitamin D-deficient HIV-1-infected patients were prospect ively treated with 2000 IU cholecalciferol/day for 14 weeks , whereafter treatment was continued with half this dosage until 48 weeks . BMD , body fat distribution , 1,25-dihydroxy vitamin D(3 ) ( 1,25(OH)2D3 ) , fasting glucose , insulin , adiponectin , leptin , interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha were measured at baseline , and at 24 and 48 weeks . Parathyroid hormone ( PTH ) , 25-hydroxy vitamin D(3 ) [ 25(OH)D(3 ) ] , cholesterol and triglycerides were measured at baseline , and at 12 , 24 and 48 weeks . RESULTS After 24 weeks , cholecalciferol supplementation significantly increased 25(OH)D3 and 1,25(OH)2D3 levels and decreased PTH and insulin sensitivity . After 48 weeks , however , only 25(OH)D3 levels remained significantly different from baseline , while the other parameter levels returned to baseline , suggesting a dose-response effect . Cholecalciferol had no effect on BMD , adipokines and triglycerides . CONCLUSIONS The effect of cholecalciferol treatment in this cohort appears to be dose dependent . Cholecalciferol dosages of > or = 2000 IU are necessary to achieve 1,25(OH)2D3 levels that significantly decrease PTH , but also negatively affect insulin sensitivity . The results of this hypothesis-driven explorative study need to be confirmed in larger clinical trials Aim /hypothesisLeptin has been shown to regulate angiogenesis in animal and in vitro studies by upregulating the production of several pro-angiogenic factors , but its role in regulating angiogenesis has never been studied in humans . Methods The potential angiogenic effect of two doses of metreleptin ( 50 and 100 ng/ml ) was evaluated in vitro , using a novel three-dimensional angiogenesis assay . Fifteen healthy , normoleptinaemic volunteers were administered both a physiological ( 0.1 mg/kg ) and a pharmacological ( 0.3 mg/kg ) single dose of metreleptin , in vivo , on two different inpatient admissions separated by 1–12 weeks . Serum was collected at 0 , 6 , 12 and 24 h after metreleptin administration . Twenty lean women , with leptin levels < 5 ng/ml , were r and omised in a 1:1 fashion to receive either physiological replacement doses of metreleptin ( 0.04–0.12 mg/kg q.d . ) or placebo for 32 weeks . Serum was collected at 0 , 8 , 20 and 32 weeks after r and omisation . Proteomic angiogenesis array analysis was performed to screen for angiogenic factors . Circulating concentrations of angiogenin , angiopoietin-1 , platelet derived endothelial factor (PDGF)-AA , matrix metalloproteinase ( MMP ) 8 and 9 , endothelial growth factor ( EGF ) and vascular EGF ( VEGF ) were also measured . Results Both metreleptin doses failed to induce angiogenesis in the in vitro model . Although leptin levels increased significantly in response to both short-term and long-term metreleptin administration , circulating concentrations of angiogenesis markers did not change significantly in vivo . Conclusions /interpretationsThis is the first study that examines the effect of metreleptin administration in angiogenesis in humans . Metreleptin administration does not regulate circulating angiogenesis related factors in humans . Clinical trial registration : Clinical Trials.gov NCT00140205 and NCT00130117 . Funding : This study was supported by National Institutes of Health-National Center for Research Re sources grant M01-RR-01032 ( Harvard Clinical and Translational Science Center ) and grant number UL1 RR025758 . Funding was also received from the National Institute of Diabetes and Digestive and Kidney Diseases grants 58785 , 79929 and 81913 , and AG032030 There is increasing epidemiological evidence linking sub-optimal vitamin D status with overweight and obesity . Although increasing BMI and adiposity have also been negatively associated with the change in vitamin D status following supplementation , results have been equivocal . The aim of this r and omised , placebo-controlled study was to investigate the associations between anthropometric measures of adiposity and the wintertime serum 25-hydroxycholecalciferol ( 25(OH)D ) response to 15 μg cholecalciferol per d in healthy young and older Irish adults . A total of 110 young adults ( 20 - 40 years ) and 102 older adults ( ≥ 64 years ) completed the 22-week intervention with > 85 % compliance . The change in 25(OH)D from baseline was calculated . Anthropometric measures of adiposity taken at baseline included height , weight and waist circumference ( WC ) , along with skinfold thickness measurements to estimate fat mass ( FM ) . FM was subsequently expressed as FM ( kg ) , FM ( % ) , FM index ( FMI ( FM kg/height m2 ) ) and as a percentage ratio to fat-free mass ( FFM ) . In older adults , vitamin D status was inversely associated with BMI ( kg/m2 ) , WC ( cm ) , FM ( kg and % ) , FMI ( kg/m2 ) and FM : FFM ( % ) at baseline ( r - 0·33 , - 0·36 , - 0·33 , - 0·30 , - 0·33 and - 0·27 , respectively , all P values < 0·01 ) . BMI in older adults was also negatively associated with the change in 25(OH)D  following supplementation ( β - 1·27 , CI - 2·37 , - 0·16 , P = 0·026 ) ; however , no such associations were apparent in younger adults . Results suggest that adiposity may need to be taken into account when determining an adequate wintertime dietary vitamin D intake for healthy older adults residing at higher latitudes Observational studies have suggested that 25-hydroxyvitamin D ( 25(OH)D ) levels are associated with inflammatory markers . Most trials reporting significant associations between vitamin D intake and inflammatory markers used specific patient groups . Thus , we aim ed to determine the effect of supplementary vitamin D using secondary data from a population -based , r and omised , placebo-controlled , double-blind trial ( Pilot D-Health trial 2010/0423 ) . Participants were 60- to 84-year-old residents of one of the four eastern states of Australia . They were r and omly selected from the electoral roll and were r and omised to one of three trial arms : placebo ( n 214 ) , 750 μg ( n 215 ) or 1500 μg ( n 215 ) vitamin D3 , each taken once per month for 12 months . Post-intervention blood sample s for the analysis of C-reactive protein ( CRP ) , IL-6 , IL-10 , leptin and adiponectin levels were available for 613 participants . Associations between intervention group and biomarker levels were evaluated using quantile regression . There were no statistically significant differences in distributions of CRP , leptin , adiponectin , leptin : adiponectin ratio or IL-10 levels between the placebo group and either supplemented group . The 75th percentile IL-6 level was 2·8 pg/ml higher ( 95 % CI 0·4 , 5·8 pg/ml ) in the 1500 μg group than in the placebo group ( 75th percentiles:11·0 v. 8·2 pg/ml ) , with a somewhat smaller , non-significant difference in 75th percentiles between the 750 μg and placebo groups . Despite large differences in serum 25(OH)D levels between the three groups after 12 months of supplementation , we found little evidence of an effect of vitamin D supplementation on cytokine or adipokine levels , with the possible exception of IL-6 The aim of this study was to assess the effects of single oral bolus of 300,000 IU Vitamin D3 on serum levels and on bone and metabolic parameters in diabetic patients . This study is a Phase IV , r and omized , double-blind , placebo-controlled , monocenter clinical trial . Thirty patients , 60 years or older , with type 2 diabetes mellitus , and diabetic foot complications , were enrolled and monitored for 24 weeks : 14 were treated with Vitamin D3 and 16 with placebo . Parameters including glucose , adiponectin , leptin , osteoprotegerin ( OPG ) , 25-hydroxyvitamin D [ 25(OH)D ] , beta-CrossLaps , osteocalcin , bone-specific isoenzyme of alkaline phosphatase , tumor necrosis factor-α and parathyroid hormone were measured at screening and baseline and 12 and 24 weeks after treatment . Analysis of covariance was used to compare treatment groups . Analysis of the data detected a significant increase in 25(OH)D serum levels both at 12 and 24 weeks 
    Output:
    
agent
Current evidence indicates that inverse association between leptin level and 25(OH)D concentration was observed in observational studies , which was not demonstrated in intervention studies with high heterogeneity .
***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 Heart and coronary calcifications in hemodialysis patients are of very common occurrence and linked to cardiovascular events and mortality . Several studies have been published with similar results . Most of them were mainly cross-sectional and some of the prospect i ve protocol s were aim ed to evaluate the results of the control of altered biochemical parameters of mineral disturbances with special regard to serum calcium , phosphate and CaxP with the use of calcium containing and calcium free phosphate chelating agents . The aim of the present study was to evaluate in hemodialysis patients classic and some non classic risk factors as predictors of calcification changes after one year and to evaluate the impact of progression on survival . Methods 81 patients on hemodialysis were studied , with a wide age range and HD vintage . Several classic parameters and some less classic risk factors were studied like fetuin-A , CRP , 25-OHD and leptin . Calcifications , as Agatston scores , were evaluated with Multislice CT basally and after 12 - 18 months . Results Coronary artery calcifications were observed in 71 of 81 patients . Non parametric correlations between Agatston scores and Age , HD Age , PTH and CRP were significant . Delta increments of Agatston scores correlated also with serum calcium , CaxP , Fetuin-A , triglycerides and serum albumin . Logistic regression analysis showed Age , PTH and serum calcium as important predictors of Delta Agatston scores . LN transformation of the not normally distributed variables restricted the significant correlations to Age , BMI and CRP . Considering the Delta Agatston scores as dependent , significant predictors were Age , PTH and HDL . A strong association was found between basal calcification scores and Delta increment at one year . By logistic analysis , the one year increments in Agatston scores were found to be predictors of mortality .  Diabetic and hypertensive patients have significantly higher Delta scores . Conclusions Progression of calcification is of common occurrence , with special regard to elevated basal scores , and is predictive of survival . Higher predictive value of survival is linked to the one year increment of calcification scores . Some classic and non classic risk factors play an important role in progression . Some of them could be controlled with appropriate management with possible improvement of mortality Background It is undetermined whether calcium supplementation has an effect on obesity or body composition in postmenopausal women . The purpose of the study is to detect the effect of calcium supplementation on indices of obesity and body composition . Methods This is a secondary analysis of data from a population -based , double-blind , placebo-controlled , r and omized trial design ed to determine the effects of calcium and vitamin D on osteoporotic fractures . The cohort included 1179 postmenopausal women who were r and omly assigned into one of three groups : 1 ) supplemental calcium ( 1400 mg/d or 1500 mg/d ) plus vitamin D placebo ( Ca-only group ) ; 2 ) supplemental calcium ( 1400 mg/d or 1500 mg/d ) plus supplemental vitamin D3 ( 1100 IU/d ) ( Ca + D group ) ; or , 3 ) two placebos ( placebo group ) . After applying the exclusion criteria for this analysis , 870 subjects were included in this study . The primary outcomes for the present study were changes in body mass index , trunk fat , trunk lean , and percentage of trunk fat after calcium supplementation . Results Changes in trunk fat , trunk lean , and percentage of trunk fat were significantly different between the calcium intervention groups ( Ca-only group or Ca + D group ) and the placebo group during the trial ( P < 0.05 ) . The calcium intervention groups gained less trunk fat and maintained more trunk lean when compared to the placebo group . No significant difference was observed for body mass index between groups . Conclusion Calcium supplementation over four years has a beneficial effect on body composition in postmenopausal women OBJECTIVE The aim of this study was to explore the effects of cholecalciferol supplementation on vitamin D levels , bone mineral density ( BMD ) , body fat distribution and insulin sensitivity in vitamin D-deficient HIV-1-infected patients . METHODS Twenty vitamin D-deficient HIV-1-infected patients were prospect ively treated with 2000 IU cholecalciferol/day for 14 weeks , whereafter treatment was continued with half this dosage until 48 weeks . BMD , body fat distribution , 1,25-dihydroxy vitamin D(3 ) ( 1,25(OH)2D3 ) , fasting glucose , insulin , adiponectin , leptin , interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha were measured at baseline , and at 24 and 48 weeks . Parathyroid hormone ( PTH ) , 25-hydroxy vitamin D(3 ) [ 25(OH)D(3 ) ] , cholesterol and triglycerides were measured at baseline , and at 12 , 24 and 48 weeks . RESULTS After 24 weeks , cholecalciferol supplementation significantly increased 25(OH)D3 and 1,25(OH)2D3 levels and decreased PTH and insulin sensitivity . After 48 weeks , however , only 25(OH)D3 levels remained significantly different from baseline , while the other parameter levels returned to baseline , suggesting a dose-response effect . Cholecalciferol had no effect on BMD , adipokines and triglycerides . CONCLUSIONS The effect of cholecalciferol treatment in this cohort appears to be dose dependent . Cholecalciferol dosages of > or = 2000 IU are necessary to achieve 1,25(OH)2D3 levels that significantly decrease PTH , but also negatively affect insulin sensitivity . The results of this hypothesis-driven explorative study need to be confirmed in larger clinical trials Aim /hypothesisLeptin has been shown to regulate angiogenesis in animal and in vitro studies by upregulating the production of several pro-angiogenic factors , but its role in regulating angiogenesis has never been studied in humans . Methods The potential angiogenic effect of two doses of metreleptin ( 50 and 100 ng/ml ) was evaluated in vitro , using a novel three-dimensional angiogenesis assay . Fifteen healthy , normoleptinaemic volunteers were administered both a physiological ( 0.1 mg/kg ) and a pharmacological ( 0.3 mg/kg ) single dose of metreleptin , in vivo , on two different inpatient admissions separated by 1–12 weeks . Serum was collected at 0 , 6 , 12 and 24 h after metreleptin administration . Twenty lean women , with leptin levels < 5 ng/ml , were r and omised in a 1:1 fashion to receive either physiological replacement doses of metreleptin ( 0.04–0.12 mg/kg q.d . ) or placebo for 32 weeks . Serum was collected at 0 , 8 , 20 and 32 weeks after r and omisation . Proteomic angiogenesis array analysis was performed to screen for angiogenic factors . Circulating concentrations of angiogenin , angiopoietin-1 , platelet derived endothelial factor (PDGF)-AA , matrix metalloproteinase ( MMP ) 8 and 9 , endothelial growth factor ( EGF ) and vascular EGF ( VEGF ) were also measured . Results Both metreleptin doses failed to induce angiogenesis in the in vitro model . Although leptin levels increased significantly in response to both short-term and long-term metreleptin administration , circulating concentrations of angiogenesis markers did not change significantly in vivo . Conclusions /interpretationsThis is the first study that examines the effect of metreleptin administration in angiogenesis in humans . Metreleptin administration does not regulate circulating angiogenesis related factors in humans . Clinical trial registration : Clinical Trials.gov NCT00140205 and NCT00130117 . Funding : This study was supported by National Institutes of Health-National Center for Research Re sources grant M01-RR-01032 ( Harvard Clinical and Translational Science Center ) and grant number UL1 RR025758 . Funding was also received from the National Institute of Diabetes and Digestive and Kidney Diseases grants 58785 , 79929 and 81913 , and AG032030 There is increasing epidemiological evidence linking sub-optimal vitamin D status with overweight and obesity . Although increasing BMI and adiposity have also been negatively associated with the change in vitamin D status following supplementation , results have been equivocal . The aim of this r and omised , placebo-controlled study was to investigate the associations between anthropometric measures of adiposity and the wintertime serum 25-hydroxycholecalciferol ( 25(OH)D ) response to 15 μg cholecalciferol per d in healthy young and older Irish adults . A total of 110 young adults ( 20 - 40 years ) and 102 older adults ( ≥ 64 years ) completed the 22-week intervention with > 85 % compliance . The change in 25(OH)D from baseline was calculated . Anthropometric measures of adiposity taken at baseline included height , weight and waist circumference ( WC ) , along with skinfold thickness measurements to estimate fat mass ( FM ) . FM was subsequently expressed as FM ( kg ) , FM ( % ) , FM index ( FMI ( FM kg/height m2 ) ) and as a percentage ratio to fat-free mass ( FFM ) . In older adults , vitamin D status was inversely associated with BMI ( kg/m2 ) , WC ( cm ) , FM ( kg and % ) , FMI ( kg/m2 ) and FM : FFM ( % ) at baseline ( r - 0·33 , - 0·36 , - 0·33 , - 0·30 , - 0·33 and - 0·27 , respectively , all P values < 0·01 ) . BMI in older adults was also negatively associated with the change in 25(OH)D  following supplementation ( β - 1·27 , CI - 2·37 , - 0·16 , P = 0·026 ) ; however , no such associations were apparent in younger adults . Results suggest that adiposity may need to be taken into account when determining an adequate wintertime dietary vitamin D intake for healthy older adults residing at higher latitudes Observational studies have suggested that 25-hydroxyvitamin D ( 25(OH)D ) levels are associated with inflammatory markers . Most trials reporting significant associations between vitamin D intake and inflammatory markers used specific patient groups . Thus , we aim ed to determine the effect of supplementary vitamin D using secondary data from a population -based , r and omised , placebo-controlled , double-blind trial ( Pilot D-Health trial 2010/0423 ) . Participants were 60- to 84-year-old residents of one of the four eastern states of Australia . They were r and omly selected from the electoral roll and were r and omised to one of three trial arms : placebo ( n 214 ) , 750 μg ( n 215 ) or 1500 μg ( n 215 ) vitamin D3 , each taken once per month for 12 months . Post-intervention blood sample s for the analysis of C-reactive protein ( CRP ) , IL-6 , IL-10 , leptin and adiponectin levels were available for 613 participants . Associations between intervention group and biomarker levels were evaluated using quantile regression . There were no statistically significant differences in distributions of CRP , leptin , adiponectin , leptin : adiponectin ratio or IL-10 levels between the placebo group and either supplemented group . The 75th percentile IL-6 level was 2·8 pg/ml higher ( 95 % CI 0·4 , 5·8 pg/ml ) in the 1500 μg group than in the placebo group ( 75th percentiles:11·0 v. 8·2 pg/ml ) , with a somewhat smaller , non-significant difference in 75th percentiles between the 750 μg and placebo groups . Despite large differences in serum 25(OH)D levels between the three groups after 12 months of supplementation , we found little evidence of an effect of vitamin D supplementation on cytokine or adipokine levels , with the possible exception of IL-6 The aim of this study was to assess the effects of single oral bolus of 300,000 IU Vitamin D3 on serum levels and on bone and metabolic parameters in diabetic patients . This study is a Phase IV , r and omized , double-blind , placebo-controlled , monocenter clinical trial . Thirty patients , 60 years or older , with type 2 diabetes mellitus , and diabetic foot complications , were enrolled and monitored for 24 weeks : 14 were treated with Vitamin D3 and 16 with placebo . Parameters including glucose , adiponectin , leptin , osteoprotegerin ( OPG ) , 25-hydroxyvitamin D [ 25(OH)D ] , beta-CrossLaps , osteocalcin , bone-specific isoenzyme of alkaline phosphatase , tumor necrosis factor-α and parathyroid hormone were measured at screening and baseline and 12 and 24 weeks after treatment . Analysis of covariance was used to compare treatment groups . Analysis of the data detected a significant increase in 25(OH)D serum levels both at 12 and 24 weeks 
    Output:
    