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 Takotsubo syndrome is a stress cardiomyopathy , characterized by reversible left ventricle ( LV ) apical ballooning in the absence of significant angiographic coronary artery stenosis . The frequent association with emotional stress suggests in this disease an autonomic nervous system involvement . We could think that a therapeutic treatment targeting heart sympathetic dysfunction could be of crucial importance . METHODS From January 2010 to June 2012 , 886 patients were consecutively evaluated at Cardarelli Hospital , Naples , Italy . Among these , 48 patients met takotsubo cardiomyopathy ( TCM ) criteria . Each patient was assessed with history and physical examination , 12-lead electrocardiogram , serum troponin , coronary arteriography , and left ventricular angiogram , perfusion myocardial scintigraphy with technetium 99 m , with echocardiography and 123I-metaiodobenzylguanidine ( MIBG ) myocardial scintigraphy . At discharge , the surviving patients were r and omly assigned to α-lipoic acid ( ALA ) treatment ( 600 mg once daily ) or placebo . Following discharge , after the initial TCM event , patients returned to our outpatient clinic at Internal Medicine of the Second University Naples for the follow-up evaluation quarterly until 12 months . Routine analysis , myocardial damage serum markers , oxidative stress serum markers , pro-inflammatory cytokines , and sympathetic tone activity were evaluated in all patients . RESULTS ALA administration improved MIBG defect size at 12 months compared to placebo . CONCLUSIONS Adrenergic cardiac innervation dysfunction in TCM patients persists after previous experience of transient stress-induced cardiac dysfunction . ALA treatment improves the adrenergic cardiac innervation . This study evaluates whether sympatho-vagal alterations are TCM event-related CONTEXT Inflammation is hypothesized to play a role in development of type 2 diabetes mellitus ( DM ) ; however , clinical data addressing this issue are limited . OBJECTIVE To determine whether elevated levels of the inflammatory markers interleukin 6 ( IL-6 ) and  C-reactive protein ( CRP ) are associated with development of  type 2 DM in healthy middle-aged women . DESIGN Prospect i ve , nested case-control study . SETTING The Women 's Health Study , an ongoing US primary prevention , r and omized clinical trial initiated in 1992 . PARTICIPANTS From a nationwide cohort of 27 628 women free of diagnosed DM , cardiovascular disease , and cancer at baseline , 188 women who developed diagnosed DM over a 4-year follow-up period were defined as cases and matched by age and fasting status with 362 disease-free controls . MAIN OUTCOME MEASURES Incidence of confirmed clinical ly diagnosed type 2 DM by baseline levels of IL-6 and CRP . RESULTS Baseline levels of IL-6 ( P<.001 ) and CRP ( P<.001 ) were significantly higher among cases than among controls . The relative risks of future DM for women in the highest vs lowest quartile of these inflammatory markers were 7.5 for IL-6 ( 95 % confidence interval [ CI ] , 3.7 - 15.4 ) and 15.7 for CRP ( 95 % CI , 6.5 - 37.9 ) . Positive associations persisted after adjustment for body mass index , family history of diabetes , smoking , exercise , use of alcohol , and hormone replacement therapy ; multivariate relative risks for the highest vs lowest quartiles were 2.3 for IL-6 ( 95 % CI , 0.9 - 5.6 ; P for trend = .07 ) and 4.2 for CRP ( 95 % CI , 1.5 - 12.0 ; P for trend = .001 ) . Similar results were observed in analyses limited to women with a baseline hemoglobin A(1c ) of 6.0 % or less and after adjustment for fasting insulin level . CONCLUSIONS Elevated levels of CRP and IL-6 predict the development of type 2 DM . These data support a possible role for inflammation in diabetogenesis Introduction Anemia associated with chronic kidney disease is a serious complication necessitating expenditure of huge medical efforts and re sources . This study investigates the role of alpha-lipoic acid ( ALA ) in end stage renal disease patients undergoing hemodialysis . By the virtue of its antioxidative effects , ALA is expected to act as an erythropoietin ( EPO ) adjuvant , and also has extended beneficial effects on endothelial dysfunction . Methods Forty-four patients undergoing hemodialysis and receiving EPO  were r and omized into two groups : the first group received ALA 600 mg once daily for 3 months ; while the other group represented the control group . Parameters measured at baseline and at end of study were hemoglobin , EPO doses , EPO resistance index ( ERI ) , iron store indices , malondialdehyde , oxidized low-density lipoprotein ( ox-LDL ) , interleukin-6 ( IL-6 ) , tumor necrosis factor-α ( TNF-α ) , and asymmetric dimethylarginine ( ADMA ) , as well as routine laboratory follow-up . Results EPO doses and ERI were significantly decreased in the treatment group , while they did not change in the control group . Hemoglobin , iron store indices , malondialdehyde , oxidized ox-LDL , IL-6 , TNF-α , and ADMA were similar in both treatment and control groups at baseline , and did not change by the end of study period . Likewise , routine laboratory measures were not affected by the treatment . Conclusion ALA could be used in hemodialysis patients to reduce requirements for EPO . However , larger and longer term studies are required to clarify the exact role of ALA in hemodialysis as well as in pre-hemodialysis patients Background Chronic renal failure is a progressive and irreversible loss of kidney function , and the hemodialysis ( HD ) is one of the most common modalities in this regard . Oxidative stresses [ like interleukin-8 ( IL-8 ) and tumor necrosis factor-alpha ( TNF-α ) ] and inflammation are the main risk factors associated with cardiovascular diseases and other complications in many organs in hemodialysis patients ; meanwhile , antioxidants like alpha lipoic acid ( ALA ) may reduce the oxidative stress markers and the levels of inflammatory cytokines , so can improve of the patient ’s quality of life . Methods In this r and omized clinical trial study , 60 HD patients were r and omly categorized in two case and control groups . Case group received a daily capsule of 600 mg of ALA supplementation for 8 weeks , and the control group received placebo capsules daily . The serum level of IL-8 and TNF-α was measured in both groups before and after the intervention . Results There were no significant differences in age , gender , duration of dialysis , and causative factor for dialysis between both groups ( P > 0.05 ) . The mean of IL-8 and TNF-α after the intervention in case group was 26.20 ± 15.34 and 21.25 ± 9.61 , respectively ; the difference between both groups was not statistically significant ( P > 0.05 ) . Conclusion Based on the better feeling and other beneficial effects of ALA were found in our study ; we can conclude that it is a beneficial and recommended supplement , especially , for diabetic and dialysis patients Background / Aim : Endothelial dysfunction due to reduced nitric oxide ( NO ) availability precedes the development of atherosclerosis . Asymmetric dimethylarginine ( ADMA ) , an endogenous inhibitor of NO synthase , is not only a cause of endothelial dysfunction , but also a predictor of the cardiovascular outcome in end-stage renal disease ( ESRD ) patients on hemodialysis ( HD ) .  α-Lipoic acid ( ALA ) , a strong antioxidant , increases NO-mediated vasodilation in diabetic patients . We investigated whether ALA could decrease the plasma level of ADMA in diabetic ESRD patients on HD . Methods : Fifty patients undergoing HD three times per week were r and omized to a treatment group receiving ALA 600 mg/day for 12 weeks or a control group . We measured the plasma levels of cholesterol , albumin , high-sensitivity C-reactive protein , oxidized low-density lipoprotein , hemoglobin A1c , and ADMA in both groups at baseline and at 12 weeks . Results : In the control group , the levels of total cholesterol , serum albumin , high-sensitivity C-reactive protein , oxidized low-density lipoprotein , hemoglobin A1c , and ADMA did not change . In the treatment group , the plasma levels of ADMA decreased significantly from a median of 1.68 ( range 0.45–3.78 ) µM to a median of 1.31 ( range 0.25–3.19 ) µM ( p = 0.001 ) . Conclusion : Considering that ADMA is an independent risk factor for cardiovascular outcome in ESRD patients  , ALA may have the potential of a beneficial effect in them , in part by decreasing the plasma level of ADMA OBJECTIVE We examined the effects of alpha-lipoic acid ( ALA ) supplementation on inflammation , oxidative stress , and serum lipid profile levels in hemodialysis ( HD ) patients . DESIGN This was a double-blinded , r and omized , placebo-controlled clinical trial . SETTING The present study involved HD centers in Tabriz , Iran . PATIENTS Participants included 63 patients with end-stage renal disease ( 43 men and 20 women ; age range : 22 - 79 years ) undergoing maintenance HD . INTERVENTION HD patients were r and omly assigned into the supplemented group ( n = 31 ) , receiving a daily dose of ALA ( 600 mg ) , or a control group ( n = 32 ) , receiving placebo for 8 weeks . MAIN OUTCOME MEASURES High sensitivity C-reactive protein ( hsCRP ) , malondialdehyde , total antioxidant status , total cholesterol , triglyceride , high-density lipoprotein cholesterol ( HDL-C ) , and low-density lipoprotein cholesterol ( LDL-C ) were measured at baseline and after 8 weeks of supplementation . RESULTS At the end of intervention , 11 patients were excluded from the study .  HsCRP levels decreased by 18.7 % in the supplemented group after 8 weeks of supplementation , and the reduction was significant in comparison with the placebo group ( P < .05 ) ; this finding was also significant after adjusting for baseline values of hsCRP . The mean malondialdehyde and total antioxidant status levels did not change significantly in the 2 groups during the study . The mean high-density lipoprotein cholesterol concentrations increased significantly in the supplemented group at the end of the study ( P < .05 ) ; however , this improvement was not statistically significant as compared with the placebo group . No significant alterations were observed in the other lipid profile parameters within each group during the study . CONCLUSION ALA supplementation significantly reduced hsCRP levels , which is a risk factor for cardiovascular disease in HD patients BACKGROUND C-reactive protein is an inflammatory marker believed to be of value in the prediction of coronary events . We report data from a large study of C-reactive protein and other circulating inflammatory markers , as well as up date d meta-analyses , to evaluate their relevance to the prediction of coronary heart disease . METHODS Measurements were made in sample s obtained at base line from up to 2459 patients who had a nonfatal myocardial infa rct ion or died of coronary heart disease during the study and from up to 3969 controls without a coronary heart disease event in the Reykjavik prospect i ve study of 18,569 participants .  Measurements were made in paired sample s obtained an average of 12 years apart from 379 of these participants in order to quantify within-person fluctuations in inflammatory marker levels . RESULTS The long-term stability of C-reactive protein values ( within-person correlation coefficient , 0.59 ; 95 percent confidence interval , 0.52 to 0.66 ) was similar to that of both blood pressure and total serum cholesterol . After adjustment for base-line values for established risk factors , the odds ratio for coronary heart disease was 1.45 ( 95 percent confidence interval , 1.25 to 1.68 ) in a comparison of participants in the top third of the group with respect to base-line C-reactive protein values with those in the bottom third , and similar overall findings were observed in an up date d meta- analysis involving a total of 7068 patients with coronary heart disease . By comparison , the odds ratios in the Reykjavik Study for coronary heart disease were somewhat weaker for the erythrocyte sedimentation rate ( 1.30 ; 95 percent confidence interval , 1.13 to 1.51 ) and the von Willebr and factor concentration ( 1.11 ; 95 percent confidence interval , 0.97 to 1.27 ) but generally stronger for established risk factors , such as an increased total cholesterol concentration ( 2.35 ; 95 percent confidence interval , 2.03 to 2.74 ) and cigarette smoking ( 1.87 ; 95 percent confidence interval , 1.62 to 2.16 ) . CONCLUSIONS C-reactive protein is a relatively moderate predictor of coronary heart disease . Recommendations 
    Output:
    
agent
Conclusion In summary , the current meta- analysis demonstrated the promising impact of ALA administration on decreasing inflammatory markers such as CRP , IL-6 and TNF-α among patients with MetS and related disorders
***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 Takotsubo syndrome is a stress cardiomyopathy , characterized by reversible left ventricle ( LV ) apical ballooning in the absence of significant angiographic coronary artery stenosis . The frequent association with emotional stress suggests in this disease an autonomic nervous system involvement . We could think that a therapeutic treatment targeting heart sympathetic dysfunction could be of crucial importance . METHODS From January 2010 to June 2012 , 886 patients were consecutively evaluated at Cardarelli Hospital , Naples , Italy . Among these , 48 patients met takotsubo cardiomyopathy ( TCM ) criteria . Each patient was assessed with history and physical examination , 12-lead electrocardiogram , serum troponin , coronary arteriography , and left ventricular angiogram , perfusion myocardial scintigraphy with technetium 99 m , with echocardiography and 123I-metaiodobenzylguanidine ( MIBG ) myocardial scintigraphy . At discharge , the surviving patients were r and omly assigned to α-lipoic acid ( ALA ) treatment ( 600 mg once daily ) or placebo . Following discharge , after the initial TCM event , patients returned to our outpatient clinic at Internal Medicine of the Second University Naples for the follow-up evaluation quarterly until 12 months . Routine analysis , myocardial damage serum markers , oxidative stress serum markers , pro-inflammatory cytokines , and sympathetic tone activity were evaluated in all patients . RESULTS ALA administration improved MIBG defect size at 12 months compared to placebo . CONCLUSIONS Adrenergic cardiac innervation dysfunction in TCM patients persists after previous experience of transient stress-induced cardiac dysfunction . ALA treatment improves the adrenergic cardiac innervation . This study evaluates whether sympatho-vagal alterations are TCM event-related CONTEXT Inflammation is hypothesized to play a role in development of type 2 diabetes mellitus ( DM ) ; however , clinical data addressing this issue are limited . OBJECTIVE To determine whether elevated levels of the inflammatory markers interleukin 6 ( IL-6 ) and  C-reactive protein ( CRP ) are associated with development of  type 2 DM in healthy middle-aged women . DESIGN Prospect i ve , nested case-control study . SETTING The Women 's Health Study , an ongoing US primary prevention , r and omized clinical trial initiated in 1992 . PARTICIPANTS From a nationwide cohort of 27 628 women free of diagnosed DM , cardiovascular disease , and cancer at baseline , 188 women who developed diagnosed DM over a 4-year follow-up period were defined as cases and matched by age and fasting status with 362 disease-free controls . MAIN OUTCOME MEASURES Incidence of confirmed clinical ly diagnosed type 2 DM by baseline levels of IL-6 and CRP . RESULTS Baseline levels of IL-6 ( P<.001 ) and CRP ( P<.001 ) were significantly higher among cases than among controls . The relative risks of future DM for women in the highest vs lowest quartile of these inflammatory markers were 7.5 for IL-6 ( 95 % confidence interval [ CI ] , 3.7 - 15.4 ) and 15.7 for CRP ( 95 % CI , 6.5 - 37.9 ) . Positive associations persisted after adjustment for body mass index , family history of diabetes , smoking , exercise , use of alcohol , and hormone replacement therapy ; multivariate relative risks for the highest vs lowest quartiles were 2.3 for IL-6 ( 95 % CI , 0.9 - 5.6 ; P for trend = .07 ) and 4.2 for CRP ( 95 % CI , 1.5 - 12.0 ; P for trend = .001 ) . Similar results were observed in analyses limited to women with a baseline hemoglobin A(1c ) of 6.0 % or less and after adjustment for fasting insulin level . CONCLUSIONS Elevated levels of CRP and IL-6 predict the development of type 2 DM . These data support a possible role for inflammation in diabetogenesis Introduction Anemia associated with chronic kidney disease is a serious complication necessitating expenditure of huge medical efforts and re sources . This study investigates the role of alpha-lipoic acid ( ALA ) in end stage renal disease patients undergoing hemodialysis . By the virtue of its antioxidative effects , ALA is expected to act as an erythropoietin ( EPO ) adjuvant , and also has extended beneficial effects on endothelial dysfunction . Methods Forty-four patients undergoing hemodialysis and receiving EPO  were r and omized into two groups : the first group received ALA 600 mg once daily for 3 months ; while the other group represented the control group . Parameters measured at baseline and at end of study were hemoglobin , EPO doses , EPO resistance index ( ERI ) , iron store indices , malondialdehyde , oxidized low-density lipoprotein ( ox-LDL ) , interleukin-6 ( IL-6 ) , tumor necrosis factor-α ( TNF-α ) , and asymmetric dimethylarginine ( ADMA ) , as well as routine laboratory follow-up . Results EPO doses and ERI were significantly decreased in the treatment group , while they did not change in the control group . Hemoglobin , iron store indices , malondialdehyde , oxidized ox-LDL , IL-6 , TNF-α , and ADMA were similar in both treatment and control groups at baseline , and did not change by the end of study period . Likewise , routine laboratory measures were not affected by the treatment . Conclusion ALA could be used in hemodialysis patients to reduce requirements for EPO . However , larger and longer term studies are required to clarify the exact role of ALA in hemodialysis as well as in pre-hemodialysis patients Background Chronic renal failure is a progressive and irreversible loss of kidney function , and the hemodialysis ( HD ) is one of the most common modalities in this regard . Oxidative stresses [ like interleukin-8 ( IL-8 ) and tumor necrosis factor-alpha ( TNF-α ) ] and inflammation are the main risk factors associated with cardiovascular diseases and other complications in many organs in hemodialysis patients ; meanwhile , antioxidants like alpha lipoic acid ( ALA ) may reduce the oxidative stress markers and the levels of inflammatory cytokines , so can improve of the patient ’s quality of life . Methods In this r and omized clinical trial study , 60 HD patients were r and omly categorized in two case and control groups . Case group received a daily capsule of 600 mg of ALA supplementation for 8 weeks , and the control group received placebo capsules daily . The serum level of IL-8 and TNF-α was measured in both groups before and after the intervention . Results There were no significant differences in age , gender , duration of dialysis , and causative factor for dialysis between both groups ( P > 0.05 ) . The mean of IL-8 and TNF-α after the intervention in case group was 26.20 ± 15.34 and 21.25 ± 9.61 , respectively ; the difference between both groups was not statistically significant ( P > 0.05 ) . Conclusion Based on the better feeling and other beneficial effects of ALA were found in our study ; we can conclude that it is a beneficial and recommended supplement , especially , for diabetic and dialysis patients Background / Aim : Endothelial dysfunction due to reduced nitric oxide ( NO ) availability precedes the development of atherosclerosis . Asymmetric dimethylarginine ( ADMA ) , an endogenous inhibitor of NO synthase , is not only a cause of endothelial dysfunction , but also a predictor of the cardiovascular outcome in end-stage renal disease ( ESRD ) patients on hemodialysis ( HD ) .  α-Lipoic acid ( ALA ) , a strong antioxidant , increases NO-mediated vasodilation in diabetic patients . We investigated whether ALA could decrease the plasma level of ADMA in diabetic ESRD patients on HD . Methods : Fifty patients undergoing HD three times per week were r and omized to a treatment group receiving ALA 600 mg/day for 12 weeks or a control group . We measured the plasma levels of cholesterol , albumin , high-sensitivity C-reactive protein , oxidized low-density lipoprotein , hemoglobin A1c , and ADMA in both groups at baseline and at 12 weeks . Results : In the control group , the levels of total cholesterol , serum albumin , high-sensitivity C-reactive protein , oxidized low-density lipoprotein , hemoglobin A1c , and ADMA did not change . In the treatment group , the plasma levels of ADMA decreased significantly from a median of 1.68 ( range 0.45–3.78 ) µM to a median of 1.31 ( range 0.25–3.19 ) µM ( p = 0.001 ) . Conclusion : Considering that ADMA is an independent risk factor for cardiovascular outcome in ESRD patients  , ALA may have the potential of a beneficial effect in them , in part by decreasing the plasma level of ADMA OBJECTIVE We examined the effects of alpha-lipoic acid ( ALA ) supplementation on inflammation , oxidative stress , and serum lipid profile levels in hemodialysis ( HD ) patients . DESIGN This was a double-blinded , r and omized , placebo-controlled clinical trial . SETTING The present study involved HD centers in Tabriz , Iran . PATIENTS Participants included 63 patients with end-stage renal disease ( 43 men and 20 women ; age range : 22 - 79 years ) undergoing maintenance HD . INTERVENTION HD patients were r and omly assigned into the supplemented group ( n = 31 ) , receiving a daily dose of ALA ( 600 mg ) , or a control group ( n = 32 ) , receiving placebo for 8 weeks . MAIN OUTCOME MEASURES High sensitivity C-reactive protein ( hsCRP ) , malondialdehyde , total antioxidant status , total cholesterol , triglyceride , high-density lipoprotein cholesterol ( HDL-C ) , and low-density lipoprotein cholesterol ( LDL-C ) were measured at baseline and after 8 weeks of supplementation . RESULTS At the end of intervention , 11 patients were excluded from the study .  HsCRP levels decreased by 18.7 % in the supplemented group after 8 weeks of supplementation , and the reduction was significant in comparison with the placebo group ( P < .05 ) ; this finding was also significant after adjusting for baseline values of hsCRP . The mean malondialdehyde and total antioxidant status levels did not change significantly in the 2 groups during the study . The mean high-density lipoprotein cholesterol concentrations increased significantly in the supplemented group at the end of the study ( P < .05 ) ; however , this improvement was not statistically significant as compared with the placebo group . No significant alterations were observed in the other lipid profile parameters within each group during the study . CONCLUSION ALA supplementation significantly reduced hsCRP levels , which is a risk factor for cardiovascular disease in HD patients BACKGROUND C-reactive protein is an inflammatory marker believed to be of value in the prediction of coronary events . We report data from a large study of C-reactive protein and other circulating inflammatory markers , as well as up date d meta-analyses , to evaluate their relevance to the prediction of coronary heart disease . METHODS Measurements were made in sample s obtained at base line from up to 2459 patients who had a nonfatal myocardial infa rct ion or died of coronary heart disease during the study and from up to 3969 controls without a coronary heart disease event in the Reykjavik prospect i ve study of 18,569 participants .  Measurements were made in paired sample s obtained an average of 12 years apart from 379 of these participants in order to quantify within-person fluctuations in inflammatory marker levels . RESULTS The long-term stability of C-reactive protein values ( within-person correlation coefficient , 0.59 ; 95 percent confidence interval , 0.52 to 0.66 ) was similar to that of both blood pressure and total serum cholesterol . After adjustment for base-line values for established risk factors , the odds ratio for coronary heart disease was 1.45 ( 95 percent confidence interval , 1.25 to 1.68 ) in a comparison of participants in the top third of the group with respect to base-line C-reactive protein values with those in the bottom third , and similar overall findings were observed in an up date d meta- analysis involving a total of 7068 patients with coronary heart disease . By comparison , the odds ratios in the Reykjavik Study for coronary heart disease were somewhat weaker for the erythrocyte sedimentation rate ( 1.30 ; 95 percent confidence interval , 1.13 to 1.51 ) and the von Willebr and factor concentration ( 1.11 ; 95 percent confidence interval , 0.97 to 1.27 ) but generally stronger for established risk factors , such as an increased total cholesterol concentration ( 2.35 ; 95 percent confidence interval , 2.03 to 2.74 ) and cigarette smoking ( 1.87 ; 95 percent confidence interval , 1.62 to 2.16 ) . CONCLUSIONS C-reactive protein is a relatively moderate predictor of coronary heart disease . Recommendations 
    Output:
    