***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: Obese subjects with impaired glucose tolerance ( IGT ) are more susceptible than healthy individuals to oxidative stress and cardiovascular disease . This r and omised controlled investigation was design ed to test the hypothesis that α-lipoic acid supplementation and exercise training may elicit favourable clinical changes in obese subjects with IGT . All data were collected from 24 obese ( BMI ≥ 30 kg/m2 ) IGT patients . Following participant r and omisation into two groups , fasting venous blood sample s were obtained at baseline , and before and following intervention . The first group consisted of 12 participants who completed a 12 week control phase followed by 12 weeks of chronic exercise at 65 % HRmax for 30 minutes a day , 5 days per week , while ingesting 1 gram per day of α-lipoic acid for 12 weeks . The second group consisted of 12 participants who completed the same 12 week control phase , but this was followed by 12 weeks of 1 gram per day of α-lipoic acid supplementation only ( no exercise ) . The main findings show a comparatively greater rate of low density lipoprotein ( LDL ) oxidation in the group consisting of α-lipoic acid only ( p < 0.05 vs. pre intervention ) , although total oxidant status was lower post intervention ( p < 0.05 vs. baseline ) in this group . However , exercise and α-lipoic acid in combination attenuates LDL oxidation . Furthermore , in the α-lipoic acid supplement plus exercise training  group , total antioxidant capacity was significantly increased ( p < 0.05 vs. baseline and pre intervention ) . Body fat percentage and waist and hip circumference decreased following exercise training ( p < 0.05 vs. post intervention ) . There were no selective treatment differences for a range of other clinical outcomes including glycaemic regulation ( p > 0.05 ) . These findings report that α-lipoic acid ingestion may increase the atherogenicity of LDL when ingested in isolation of exercise , suggesting that in IGT the use of this antioxidant treatment does not ameliorate metabolic disturbances , but instead may detrimentally contribute to the pathogenesis of atherosclerosis and development of CVD . However , when α-lipoic acid is combined with exercise , this atherogenic effect is abolished Objectives : To evaluate the effect of ubiquinone and combined antioxidant therapy on mitochondrial function in non-proliferative diabetic retinopathy ( NPDR ) in a r and omized , double-blind , phase IIa , placebo-controlled , clinical trial . Three groups of 20 patients were formed : Group 1 , ubiquinone ; Group 2 , combined therapy ; and Group 3 , placebo ( one daily dose for 6 months ) . Methods : Fluidity of the su bmi tochondrial membrane in platelets was determined by examining intensity of fluorescence between the monomer ( I m ) and excimer ( Ie ) . Hydrolytic activity of the mitochondrial F0F1-ATPase was evaluated with the spectrophotometric method . Results : Normal , baseline su bmi tochondrial membrane fluidity , 0.24 ± 0.01 Ie/Im , was significantly diminished in the three study groups vs. normal values ( P < 0.0001 ) ; placebo , 0.14 ± 0.01 Ie/Im ; ubiquinone , 0.14 ± 0.01 Ie/Im ; and combined therapy , 0.13 ± 0.00 Ie/Im . Afterward , it increased significantly ( P < 0.0001 ) , the ubiquinone group 0.22 ± 0.01 Ie/Im , combined therapy group , 0.19 ± 0.01 Ie/Im ; with no changes the placebo group . Baseline hydrolytic activity of the F0F1-ATPase enzyme increased in the three study groups vs. normal values ( 184.50 ± 7.84 nmol PO4 ) , placebo , 304.12 ± 22.83 nmol PO4 ( P < 0.002 ) ; ubiquinone , 312.41 ± 25.63 nmol PO4 ( P < 0.009 ) ; and combined therapy , 371.28 ± 33.50 nmol PO4 ( P < 0.002 ) . Afterward , a significant decrease the enzymatic activity : ubiquinone , 213.25 ± 14.19 nmol PO4 ( P < 0.001 ) ; and combined therapy , 225.55 ± 14.48 nmol PO4 ( P < 0.0001 ) . Discussion : Mitochondrial dysfunction significantly improved in groups of NPDR patients treated with antioxidants Objective To evaluate the effect of ubiquinone ( Coenzyme Q10 ) and combined antioxidant therapy ( CAT ) on oxidative stress markers in non-proliferative diabetic retinopathy ( NPDR ) under clinical management . Study design In a r and omized , double-blind , phase IIa , placebo-controlled , clinical trial , three study groups were formed and administered medications as follows : Group 1 , Coenzyme Q10 ; Group 2 , CAT ; and Group 3 , placebo . Methods Serum levels of the products of lipid peroxidation ( LPO ) and nitrites/nitrates , as markers of oxidative/nitrosative stress , were measured . As antioxidants , the total antioxidant capacity ( TAC ) , catalase activity , and glutathione peroxidase ( GPx ) activity were measured . Results Baseline serum levels of LPO and nitrites/nitrates were significantly elevated in the three groups vs. healthy group ( P < 0.0001 ) , while final levels in the Coenzyme Q10 and CAT groups were decreased vs. normal levels ( P < 0.0001 ) . The baseline TAC was consumed in the three groups ( P < 0.0001 ) , while final results in the Coenzyme Q10 and CAT groups improved ( P < 0.0001 ) . Baseline catalase activity was increased in all groups vs. normal values ( P < 0.001 ) , while final levels in the Coenzyme Q10 ( P < 0.001 ) and CAT groups ( P < 0.0001 ) were decreased . GPx behaved similarly to catalase and improved in the final results ( P < 0.0001 ) . Discussion Adjunctive antioxidant treatment for 6 months was effective and safe for improving the oxidative stress in NPDR Aims : The aim was to evaluate circulating levels of reactive oxygen species ( ROS ) and changes in central macular thickness ( CMT ) in patients with nonproliferative diabetic retinopathy ( NPDR ) after antioxidant supplementation . Material s and Methods : A total of 68 patients ( 68 eyes ) with NPDR were enrolled . Patients were r and omly divided into two groups : Treated with antioxidant supplement ( Group A ) and untreated control group ( Group B ) . Each tablet , for oral administration , containing pycnogenol 50 mg , Vitamin E 30 mg and coenzyme Q10 20 mg .  CMT and free oxygen radical test ( FORT )  were analyzed at baseline ( T0 ) , 3 ( T1 ) and 6 ( T2 ) months in both groups . Results : In Group A , FORT levels and CMT were significantly reduced over time ( P < 0.001 for both ) . In Group B , FORT levels were increased ( P < 0.001 ) and CMT did not vary significantly ( P = 0.81 ) over 3 time points . Conclusions : This is the first study showing the reduction of ROS levels in patients with NPDR thanks to antioxidant therapy . Moreover , our findings have suggested also an influence on retinal thickness Background Dealing with heterogeneity in meta-analyses is often tricky , and there is only limited advice for authors on what to do . We investigated how authors addressed different degrees of heterogeneity , in particular whether they used a fixed effect model , which assumes that all the included studies are estimating the same true effect , or a r and om effects model where this is not assumed . Methods We sample d r and omly 60 Cochrane review s from 2008 , which presented a result in its first meta- analysis with substantial heterogeneity ( I2 greater than 50 % , i.e. more than 50 % of the variation is due to heterogeneity rather than chance ) . We extracted information on choice of statistical model , how the authors had h and led the heterogeneity , and assessed the method ological quality of the review s in relation to this . Results The distribution of heterogeneity was rather uniform in the whole I2 interval , 50 - 100 % . A fixed effect model was used in 33 review s ( 55 % ) , but there was no correlation between I2 and choice of model ( P = 0.79 ) . We considered that 20 review s ( 33 % ) , 16 of which had used a fixed effect model , had major problems . The most common problems were : use of a fixed effect model and lack of rationale for choice of that model , lack of comment on even severe heterogeneity and of reservations and explanations of its likely causes . The problematic review s had significantly fewer included trials than other review s ( 4.3 vs. 8.0 , P = 0.024 ) . The problems became less pronounced with time , as those review s that were most recently up date d more often used a r and om effects model . Conclusion One-third of Cochrane review s with substantial heterogeneity had major problems in relation to their h and ling of heterogeneity . More attention is needed to this issue , as the problems we identified can be essential for the conclusions of the review Statins are potent cholesterol-lowering drugs and are generally well tolerated . Hepatotoxicity is a rare but serious adverse effect of statins ; however , its mechanisms are not clear . Coenzyme Q10 deficiency has been suggested , and supplementation of reduced coenzyme Q10 ( ubiquinol ) has been shown to have hepatoprotective effects . MicroRNAs ( miRNAs ) are small nucleotides that have been shown to be up-regulated in drug-induced liver injury . We hypothesized that circulating miRNAs may be differentially regulated after simvastatin treatment and by comparing with that of simvastatin and ubiquinol supplementation could potentially uncover signatory miRNA profile for simvastatin-induced liver injury . In this double-blind , prospect i ve , r and omized-controlled trial , miRNA profiles and liver enzymes were compared between simvastatin-treated patients , with and without ubiquinol supplementation , over 12 weeks compared to baseline . miRNA expression was further vali date d in HepG2 liver cell lines by real-time PCR . Changes in miR-192 , miR-146a , miR-148a , miR-15a , and miR-21 were positively correlated ( p<0.05 ) with alanine aminotransferase in  simvastatin-only  treated patients . In ubiquinol supplementation group , alanine aminotransferase and alkaline phosphatase were significantly down-regulated after 12 weeks and changes in miR-15a , miR-21 and miR-33a were negatively correlated with alkaline phosphatase ( p < 0.05 ) . Bioinformatics analyses predicted that miRNA regulation in simvastatin group was related to reduce proliferation and adenosine triphosphate-binding cassette transporters .  Ubiquinol supplementation additionally regulated miRNAs that inhibit apoptotic and inflammatory pathways , suggesting potential hepatoprotective effects . Our results suggest that 20 mg/day of simvastatin does not have significant risk of hepatotoxicity and ubiquinol supplementation may , at the miRNA level , provide potential beneficial changes to reduce the effects of coenzyme Q10 deficiency in the liver Background : Adipolin , the novel adipokine that is proposed to be reduced in diabetes , obesity and inflammation , may improve glycemic control . It is known that coenzyme Q10 could improve insulin sensitivity . The aim of the current study was to investigate the effect of Q10 supplementation on adipolin concentration and glucose metabolism in overweight and obese diabetic patients . Material & Methods : Sixty four patients with type 2 diabetes and 25 < BMI < 35 kg/m2 were r and omly divided to receive 200 mg Q10 or placebo daily for 12 weeks . Fasting serum levels of adipolin , glucose , insulin , HbA1c and HOMA-IR were measured before and after supplementation . Results : Following supplementation , adipolin levels decreased significantly in Q10 group ( 38.19±32.02 to 29.03±34.23 ng/ml;P=0.001 ) . HbA1c decreased dramatically following supplementation only in Q10 group ( 8.6±2.2 % to 7.9±2.1 % , P<0.001 ) . It was also marginally lower in Q10 compared to placebo group at the end of study ( P=0.056 ) . Moreover , weight ( P=0.003 ) , BMI ( P=0.003 ) and waist circumference ( P=0.016 ) decreased significantly in Q10 group . No significant alterations were observed in FBS , fasting insulin and HOMA-IR within or between Q10 and placebo groups . Conclus 
    Output:
    
Conclusions The overall results demonstrated that supplementation with CoQ10 shows an enhanced potential to lower CVD risk  in diabetic patients by reducing total cholesterol and LDL .
Moreover , the beneficial effects of CoQ10 in lowering the CVD risk are associated with its ameliorative properties against oxidative stress and improving endothelial health