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 Women with polycystic ovary syndrome ( PCOS ) have symptoms of depression and anxiety and impaired health related quality of life ( HRQoL ) . Here we test the post-hoc hypothesis that acupuncture and exercise improve depression and anxiety symptoms and HRQoL in PCOS women . Methods Seventy-two PCOS women were r and omly assigned to 16 weeks of 1 ) acupuncture ( n = 28 ) ; 2 ) exercise ( n = 29 ) ; or 3 ) no intervention ( control ) ( n = 15 ) . Outcome measures included : change in Montgomery Åsberg Depression Rating Scale ( MADRS-S ) , Brief Scale for Anxiety ( BSA-S ) , Swedish Short-Form 36 ( SF-36 ) , and PCOS Question naire ( PCOSQ ) scores from baseline to after 16-week intervention , and to 16-week post-intervention follow-up . Results A reduction in MADRS-S and BSA-S from baseline to 16-weeks post-intervention follow-up was observed for the acupuncture group . The SF-36 domains role physical , energy/vitality , general health perception and the mental component of summary scores improved in the acupuncture group after intervention and at follow-up . Within the exercise group the role physical decreased after treatment , while physical functioning and general health perception scores increased at follow-up . The emotion domain in the PCOSQ improved after 16-weeks of intervention within all three groups , and at follow-up in acupuncture and exercise groups . At follow-up , improvement in the infertility domain was observed within the exercise group . Conclusion There was a modest improvement in depression and anxiety scores  in women treated with  acupuncture  , and improved HRQoL scores were noted in both intervention groups . While not a primary focus of the trial , these data suggest continued investigation of mental health outcomes in women treated for PCOS.Trial registration number Clinical Trials.gov Identifier : Background — Although dietary folate fortification lowers plasma homocysteine and may reduce cardiovascular risk , high-dose folic acid therapy appears to not alter clinical outcome . Folic acid and its principal circulating metabolite , 5-methyltetrahydrofolate , improve vascular function , but mechanisms relating folate dose to vascular function remain unclear . We compared the effects of folic acid on human vessels using pharmacological high-dose versus low-dose treatment , equivalent to dietary folate fortification . Methods and Results — Fifty-six non – folate-fortified patients with coronary artery disease were r and omized to receive low-dose ( 400 & mgr;g/d ) or high-dose ( 5 mg/d ) folic acid or placebo for 7 weeks before coronary artery bypass grafting . Vascular function was quantified by magnetic resonance imaging before and after treatment . Vascular superoxide and nitric oxide bioavailability were determined in segments of saphenous vein and internal mammary artery . Low-dose folic acid increased nitric oxide – mediated endothelium-dependent vasomotor responses , reduced vascular superoxide production , and improved enzymatic coupling of endothelial nitric oxide synthase through availability of the cofactor tetrahydrobiopterin . No further improvement in these parameters occurred with high-dose compared with low-dose treatment . Whereas plasma 5-methyltetrahydrofolate increased proportionately with treatment dose of folic acid , vascular tissue 5-methyltetrahydrofolate showed no further increment with high-dose compared with low-dose folic acid . Conclusions — Low-dose folic acid treatment , comparable to daily intake and dietary fortification , improves vascular function through effects on endothelial nitric oxide synthase and vascular oxidative stress . High-dose folic acid treatment provides no additional benefit . These direct vascular effects are related to vascular tissue levels of 5-methyltetrahydrofolate rather than plasma levels . High-dose folic acid treatment likely confers no further benefit in subjects already receiving folate supplementation AIM The aim of this study was to evaluate the effect of oral N-acetylcysteine ( NAC ) administration as an adjuvant to clomiphene citrate ( CC ) on induction of ovulation outcomes in patients with polycystic ovary syndrome ( PCOS ) . MATERIAL AND METHODS In this placebo-controlled double-blind r and omized clinical trial , 180 PCOS infertile patients were r and omly divided into two groups for induction of ovulation . Patients in group 1 received CC 100 mg/d plus NAC 1.2 g/d and patients in group 2 received CC plus placebo for 5 days starting at day 3 of the cycle . On the 12th day of the menstrual cycle in the presence of at least one follicle with an 18 - 20-mm diameter in ultrasound evaluation , 10,000 U hCG was injected intramuscularly and timed intercourse was advised 36 h after hCG injection . Serum β-hCG level was measured on the 16th day after hCG injection . RESULTS The number of follicles > 18 mm and the mean endometrial thickness on the day of hCG administration were significantly higher among the CC+NAC group ( P-value = 0.001 ) . The ovulation and pregnancy rates were also significantly higher in the CC+NAC group ( P-value = 0.02 and 0.04 , respectively ) . No adverse side-effects and no cases of ovarian hyperstimulation syndrome were observed in the group receiving NAC . CONCLUSION NAC as a safe and well-tolerated adjuvant to CC for induction of ovulation can improve the ovulation and pregnancy rates in PCOS patients . It may also have some beneficial impacts on endometrial thickness BACKGROUND Oxidative damage to lipids may be involved in the etiology of atherosclerosis , cardiovascular disease in general , and cancer . The soy isoflavone phytoestrogens , genistein and daidzein , and equol ( a daidzein metabolite produced by intestinal microflora ) are antioxidants in vitro ; equol is a particularly good inhibitor of LDL oxidation and membrane lipid peroxidation . OBJECTIVE We sought to investigate the effects of a diet enriched with soy containing isoflavones on in vivo biomarkers of lipid peroxidation and resistance of LDL to oxidation , compared with a diet enriched with soy from which the isoflavones had been extracted . DESIGN : A r and omized , crossover design was used to compare diets enriched with soy that was low or high in isoflavones in 24 subjects .  Plasma concentrations of an F(2)-isoprostane , 8-epi-prostagl and in F(2)(alpha ) ( 8-epi-PGF(2)(alpha ) ) , a biomarker of in vivo lipid peroxidation , and resistance of LDL to copper-ion-induced oxidation were determined . RESULTS Plasma concentrations of 8-epi-PGF(2)(alpha ) were significantly lower after the high-isoflavone dietary treatment than after the low-isoflavone dietary treatment ( 326 + /- 32 and 405 + /- 50 ng/L , respectively ; P = 0.028 ) and the lag time for copper-ion-induced LDL oxidation was longer ( 48 + /- 2.4 and 44 + /- 1.9 min , respectively ; P = 0.017 ) . Lag time for oxidation of unfractionated plasma and plasma concentrations of malondialdehyde , LDL alpha-tocopherol , polyunsaturated fatty acids , and isoflavonoids did not differ significantly between dietary treatments . CONCLUSIONS Consumption of soy containing naturally occurring amounts of isoflavone phytoestrogens reduced lipid peroxidation in vivo and increased the resistance of LDL to oxidation . This antioxidant action may be significant with regard to risk of atherosclerosis , cardiovascular disease in general , and cancer Objective . To compare clomiphene citrate plus N‐acetyl cysteine versus clomiphene citrate for inducing ovulation in patients with polycystic ovary syndrome . Design . Prospect i ve cross‐over trial . Setting . University teaching hospital and a private practice setting . Patients . Five hundred and seventy‐three patients were treated with clomiphene citrate for one menstrual cycle among which 470 patients were treated with clomiphene citrate plus N‐acetyl cysteine for another cycle . All women suffered from polycystic ovary syndrome . Interventions . Patients had clomiphene citrate 50‐mg tablets twice daily alone or with N‐acetyl cysteine 1,200 mg/day orally for 5 days starting on day 3 of the menstrual cycle . Outcome measures . Primary outcomes were number of mature follicles , serum E2 , serum progesterone , and endometrial thickness . Secondary outcome was the occurrence of pregnancy . Results . Ovulation rate improved significantly after the addition of N‐acetyl cysteine ( 17.9 % versus 52.1 % ) . Although the number of mature follicles was more in the N‐acetyl cysteine group ( 2.1±0.88 versus 3.2±0.93 ) , the difference was not statistically significant . The mean E2 levels ( pg/ml ) at the time of human chorionic gonadotropine injection , serum progesterone levels ( ng/ml ) on days 21–23 of the cycle , and the endometrial thickness were significantly improved in the N‐acetyl cysteine group . The overall pregnancy rate was 11.5 % in the N‐acetyl cysteine group .  Insulin resistance occurred in 260 patients ( 55.4 % ) . There was no significant difference between the insulin resistance group ( n = 260 ) and non‐insulin resistance group ( n = 210 ) as regards ovulation rate , number of follicles , serum E2 ( pg/ml ) , serum progesterone ( ng/ml ) , endometrial thickness ( mm ) , or pregnancy rate . Conclusion . N‐Acetyl cysteine is proved effective in inducing or augmenting ovulation in polycystic ovary patients OBJECTIVE To evaluate whether the administration of metformin exerts any effects on serum homocysteine ( Hcy ) levels in patients with polycystic ovary syndrome ( PCOS ) and whether supplementation with folate enhances the positive effects of metformin on the structure and function of the vascular endothelium . RESEARCH DESIGN AND METHODS A total of 50 patients affected by PCOS , without additional metabolic or cardiovascular diseases , were enrolled in a prospect i ve nonr and omized placebo-controlled double-blind clinical study . They were grouped into two treatment arms that were matched for age and BMI . Patients were treated with a 6-month course of metformin ( 1,700 mg daily ) plus folic acid ( 400 μg daily ; experimental group , n = 25 ) or placebo ( control group , n = 25 ) . Complete hormonal and metabolic patterns , serum Hcy , folate , vitamin B12 , endothelin-1 levels , brachial artery diameter at the baseline ( BAD-B ) and after reactive hyperemia ( BAD-RH ) , flow-mediated dilation , and intima-media thickness in both common carotid arteries were evaluated . RESULTS After treatment , a significant increase in serum Hcy levels was observed in the control group compared with the baseline values and the experimental group . A beneficial effect was observed in the concentrations of BAD-B , BAD-RH , flow-mediated dilation , intima-media thickness , and serum endothelin-1 in both groups . However , the results were improved more significantly in the experimental group than in the control subjects . CONCLUSIONS Metformin exerts a slight but significant deleterious effect on serum Hcy levels in patients with PCOS , and supplementation with folate is useful to increase the beneficial effect of metformin on the vascular endothelium The aim of this study was to test the influence of high-dose folic acid ( 10 mg/d ) on endothelial function in patients referred for coronary intervention after an acute myocardial infa rct ion ( AMI ) and determine its relation to homocysteine levels . Flow-mediated dilation ( FMD ) of the brachial artery was performed in 40 patients after AMI ( 16 with normal homocysteine levels and 24 patients with elevated levels [ > 11 micromol/L ] ) . Subjects were r and omized to receive first folic acid ( 10 mg/day ; group A ) or placebo ( group B ) for 6 weeks in a double-blind crossover trial with a 2-week washout . Plasma folate , total homocysteine and its subtypes ( oxidized , reduced , and protein-bound ) , FMD , and nitroglycerin-mediated dilation were assessed at baseline and at 6 and 14 weeks . In group A , folic acid improved FMD from 3.98 + /- 0.35 % to 6.44 + /- 0.56 % ( p < 0.001 ) . This effect persisted after the crossover with placebo ( 5.42 + /- 0.59 , p = 0.13 ) . In group B , placebo did not increase FMD ( 4.01 + /- 0.34 % vs 4.46 + /- 0.38 , p 
    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 Women with polycystic ovary syndrome ( PCOS ) have symptoms of depression and anxiety and impaired health related quality of life ( HRQoL ) . Here we test the post-hoc hypothesis that acupuncture and exercise improve depression and anxiety symptoms and HRQoL in PCOS women . Methods Seventy-two PCOS women were r and omly assigned to 16 weeks of 1 ) acupuncture ( n = 28 ) ; 2 ) exercise ( n = 29 ) ; or 3 ) no intervention ( control ) ( n = 15 ) . Outcome measures included : change in Montgomery Åsberg Depression Rating Scale ( MADRS-S ) , Brief Scale for Anxiety ( BSA-S ) , Swedish Short-Form 36 ( SF-36 ) , and PCOS Question naire ( PCOSQ ) scores from baseline to after 16-week intervention , and to 16-week post-intervention follow-up . Results A reduction in MADRS-S and BSA-S from baseline to 16-weeks post-intervention follow-up was observed for the acupuncture group . The SF-36 domains role physical , energy/vitality , general health perception and the mental component of summary scores improved in the acupuncture group after intervention and at follow-up . Within the exercise group the role physical decreased after treatment , while physical functioning and general health perception scores increased at follow-up . The emotion domain in the PCOSQ improved after 16-weeks of intervention within all three groups , and at follow-up in acupuncture and exercise groups . At follow-up , improvement in the infertility domain was observed within the exercise group . Conclusion There was a modest improvement in depression and anxiety scores  in women treated with  acupuncture  , and improved HRQoL scores were noted in both intervention groups . While not a primary focus of the trial , these data suggest continued investigation of mental health outcomes in women treated for PCOS.Trial registration number Clinical Trials.gov Identifier : Background — Although dietary folate fortification lowers plasma homocysteine and may reduce cardiovascular risk , high-dose folic acid therapy appears to not alter clinical outcome . Folic acid and its principal circulating metabolite , 5-methyltetrahydrofolate , improve vascular function , but mechanisms relating folate dose to vascular function remain unclear . We compared the effects of folic acid on human vessels using pharmacological high-dose versus low-dose treatment , equivalent to dietary folate fortification . Methods and Results — Fifty-six non – folate-fortified patients with coronary artery disease were r and omized to receive low-dose ( 400 & mgr;g/d ) or high-dose ( 5 mg/d ) folic acid or placebo for 7 weeks before coronary artery bypass grafting . Vascular function was quantified by magnetic resonance imaging before and after treatment . Vascular superoxide and nitric oxide bioavailability were determined in segments of saphenous vein and internal mammary artery . Low-dose folic acid increased nitric oxide – mediated endothelium-dependent vasomotor responses , reduced vascular superoxide production , and improved enzymatic coupling of endothelial nitric oxide synthase through availability of the cofactor tetrahydrobiopterin . No further improvement in these parameters occurred with high-dose compared with low-dose treatment . Whereas plasma 5-methyltetrahydrofolate increased proportionately with treatment dose of folic acid , vascular tissue 5-methyltetrahydrofolate showed no further increment with high-dose compared with low-dose folic acid . Conclusions — Low-dose folic acid treatment , comparable to daily intake and dietary fortification , improves vascular function through effects on endothelial nitric oxide synthase and vascular oxidative stress . High-dose folic acid treatment provides no additional benefit . These direct vascular effects are related to vascular tissue levels of 5-methyltetrahydrofolate rather than plasma levels . High-dose folic acid treatment likely confers no further benefit in subjects already receiving folate supplementation AIM The aim of this study was to evaluate the effect of oral N-acetylcysteine ( NAC ) administration as an adjuvant to clomiphene citrate ( CC ) on induction of ovulation outcomes in patients with polycystic ovary syndrome ( PCOS ) . MATERIAL AND METHODS In this placebo-controlled double-blind r and omized clinical trial , 180 PCOS infertile patients were r and omly divided into two groups for induction of ovulation . Patients in group 1 received CC 100 mg/d plus NAC 1.2 g/d and patients in group 2 received CC plus placebo for 5 days starting at day 3 of the cycle . On the 12th day of the menstrual cycle in the presence of at least one follicle with an 18 - 20-mm diameter in ultrasound evaluation , 10,000 U hCG was injected intramuscularly and timed intercourse was advised 36 h after hCG injection . Serum β-hCG level was measured on the 16th day after hCG injection . RESULTS The number of follicles > 18 mm and the mean endometrial thickness on the day of hCG administration were significantly higher among the CC+NAC group ( P-value = 0.001 ) . The ovulation and pregnancy rates were also significantly higher in the CC+NAC group ( P-value = 0.02 and 0.04 , respectively ) . No adverse side-effects and no cases of ovarian hyperstimulation syndrome were observed in the group receiving NAC . CONCLUSION NAC as a safe and well-tolerated adjuvant to CC for induction of ovulation can improve the ovulation and pregnancy rates in PCOS patients . It may also have some beneficial impacts on endometrial thickness BACKGROUND Oxidative damage to lipids may be involved in the etiology of atherosclerosis , cardiovascular disease in general , and cancer . The soy isoflavone phytoestrogens , genistein and daidzein , and equol ( a daidzein metabolite produced by intestinal microflora ) are antioxidants in vitro ; equol is a particularly good inhibitor of LDL oxidation and membrane lipid peroxidation . OBJECTIVE We sought to investigate the effects of a diet enriched with soy containing isoflavones on in vivo biomarkers of lipid peroxidation and resistance of LDL to oxidation , compared with a diet enriched with soy from which the isoflavones had been extracted . DESIGN : A r and omized , crossover design was used to compare diets enriched with soy that was low or high in isoflavones in 24 subjects .  Plasma concentrations of an F(2)-isoprostane , 8-epi-prostagl and in F(2)(alpha ) ( 8-epi-PGF(2)(alpha ) ) , a biomarker of in vivo lipid peroxidation , and resistance of LDL to copper-ion-induced oxidation were determined . RESULTS Plasma concentrations of 8-epi-PGF(2)(alpha ) were significantly lower after the high-isoflavone dietary treatment than after the low-isoflavone dietary treatment ( 326 + /- 32 and 405 + /- 50 ng/L , respectively ; P = 0.028 ) and the lag time for copper-ion-induced LDL oxidation was longer ( 48 + /- 2.4 and 44 + /- 1.9 min , respectively ; P = 0.017 ) . Lag time for oxidation of unfractionated plasma and plasma concentrations of malondialdehyde , LDL alpha-tocopherol , polyunsaturated fatty acids , and isoflavonoids did not differ significantly between dietary treatments . CONCLUSIONS Consumption of soy containing naturally occurring amounts of isoflavone phytoestrogens reduced lipid peroxidation in vivo and increased the resistance of LDL to oxidation . This antioxidant action may be significant with regard to risk of atherosclerosis , cardiovascular disease in general , and cancer Objective . To compare clomiphene citrate plus N‐acetyl cysteine versus clomiphene citrate for inducing ovulation in patients with polycystic ovary syndrome . Design . Prospect i ve cross‐over trial . Setting . University teaching hospital and a private practice setting . Patients . Five hundred and seventy‐three patients were treated with clomiphene citrate for one menstrual cycle among which 470 patients were treated with clomiphene citrate plus N‐acetyl cysteine for another cycle . All women suffered from polycystic ovary syndrome . Interventions . Patients had clomiphene citrate 50‐mg tablets twice daily alone or with N‐acetyl cysteine 1,200 mg/day orally for 5 days starting on day 3 of the menstrual cycle . Outcome measures . Primary outcomes were number of mature follicles , serum E2 , serum progesterone , and endometrial thickness . Secondary outcome was the occurrence of pregnancy . Results . Ovulation rate improved significantly after the addition of N‐acetyl cysteine ( 17.9 % versus 52.1 % ) . Although the number of mature follicles was more in the N‐acetyl cysteine group ( 2.1±0.88 versus 3.2±0.93 ) , the difference was not statistically significant . The mean E2 levels ( pg/ml ) at the time of human chorionic gonadotropine injection , serum progesterone levels ( ng/ml ) on days 21–23 of the cycle , and the endometrial thickness were significantly improved in the N‐acetyl cysteine group . The overall pregnancy rate was 11.5 % in the N‐acetyl cysteine group .  Insulin resistance occurred in 260 patients ( 55.4 % ) . There was no significant difference between the insulin resistance group ( n = 260 ) and non‐insulin resistance group ( n = 210 ) as regards ovulation rate , number of follicles , serum E2 ( pg/ml ) , serum progesterone ( ng/ml ) , endometrial thickness ( mm ) , or pregnancy rate . Conclusion . N‐Acetyl cysteine is proved effective in inducing or augmenting ovulation in polycystic ovary patients OBJECTIVE To evaluate whether the administration of metformin exerts any effects on serum homocysteine ( Hcy ) levels in patients with polycystic ovary syndrome ( PCOS ) and whether supplementation with folate enhances the positive effects of metformin on the structure and function of the vascular endothelium . RESEARCH DESIGN AND METHODS A total of 50 patients affected by PCOS , without additional metabolic or cardiovascular diseases , were enrolled in a prospect i ve nonr and omized placebo-controlled double-blind clinical study . They were grouped into two treatment arms that were matched for age and BMI . Patients were treated with a 6-month course of metformin ( 1,700 mg daily ) plus folic acid ( 400 μg daily ; experimental group , n = 25 ) or placebo ( control group , n = 25 ) . Complete hormonal and metabolic patterns , serum Hcy , folate , vitamin B12 , endothelin-1 levels , brachial artery diameter at the baseline ( BAD-B ) and after reactive hyperemia ( BAD-RH ) , flow-mediated dilation , and intima-media thickness in both common carotid arteries were evaluated . RESULTS After treatment , a significant increase in serum Hcy levels was observed in the control group compared with the baseline values and the experimental group . A beneficial effect was observed in the concentrations of BAD-B , BAD-RH , flow-mediated dilation , intima-media thickness , and serum endothelin-1 in both groups . However , the results were improved more significantly in the experimental group than in the control subjects . CONCLUSIONS Metformin exerts a slight but significant deleterious effect on serum Hcy levels in patients with PCOS , and supplementation with folate is useful to increase the beneficial effect of metformin on the vascular endothelium The aim of this study was to test the influence of high-dose folic acid ( 10 mg/d ) on endothelial function in patients referred for coronary intervention after an acute myocardial infa rct ion ( AMI ) and determine its relation to homocysteine levels . Flow-mediated dilation ( FMD ) of the brachial artery was performed in 40 patients after AMI ( 16 with normal homocysteine levels and 24 patients with elevated levels [ > 11 micromol/L ] ) . Subjects were r and omized to receive first folic acid ( 10 mg/day ; group A ) or placebo ( group B ) for 6 weeks in a double-blind crossover trial with a 2-week washout . Plasma folate , total homocysteine and its subtypes ( oxidized , reduced , and protein-bound ) , FMD , and nitroglycerin-mediated dilation were assessed at baseline and at 6 and 14 weeks . In group A , folic acid improved FMD from 3.98 + /- 0.35 % to 6.44 + /- 0.56 % ( p < 0.001 ) . This effect persisted after the crossover with placebo ( 5.42 + /- 0.59 , p = 0.13 ) . In group B , placebo did not increase FMD ( 4.01 + /- 0.34 % vs 4.46 + /- 0.38 , p 
    Output:
    