Effects of lifestyle interventions on glucose regulation and diabetes risk in adults with impaired glucose tolerance or prediabetes: a meta-analysis

ABSTRACT The prevalence of diabetes mellitus is increasing and is related to sedentary lifestyles and obesity. Many studies were published on the effect of lifestyle interventions on glucose regulation and delay the onset of diabetes in adults with impaired glucose tolerance (IGT) or prediabetes. This study aimed to investigate the role of lifestyle interventions in individuals with IGT or prediabetes using a meta-analytic approach. PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases were searched from their inception up to January 2020 to select eligible randomized controlled trials (RCTs). The weighted mean difference (WMD; for fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPPG)) or relative risk (RR; for the risk of diabetes) with 95% confidence interval (CI) were calculated for pooled effect estimates using the random-effects model. Thirteen RCTs involving 3376 individuals with IGT or prediabetes were selected for this meta-analysis. The results showed that lifestyle interventions were associated with lower FPG (WMD: -0.14; 95% CI: -0.24 to -0.05 mmol/L; p=0.004) and 2hPPG (WMD: -0.66; 95% CI: -1.12 to -0.20 mmol/L; p=0.005) in adults with IGT or prediabetes. Moreover, the risk of diabetes was significantly reduced in individuals who received lifestyle interventions (RR: 0.75; 95% CI: 0.60-0.95; p=0.015). Lifestyle interventions could help improve glucose dysregulation and prevent the progression of diabetes in adults with IGT or prediabetes. Further large-scale RCTs should be conducted to assess the effects of long-term lifestyle interventions on diabetic complications in adults with IGT or prediabetes.

Effects of lifestyle interventions on glucose regulation and diabetes risk in adults with impaired glucose tolerance or prediabetes: a meta-analysis.

The prevalence of diabetes mellitus is increasing and is related to sedentary lifestyles and obesity. Many studies were published on the effect of lifestyle interventions on glucose regulation and delay the onset of diabetes in adults with impaired glucose tolerance (IGT) or prediabetes. This study aimed to investigate the role of lifestyle interventions in individuals with IGT or prediabetes using a meta-analytic approach. PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases were searched from their inception up to January 2020 to select eligible randomized controlled trials (RCTs). The weighted mean difference (WMD; for fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPPG)) or relative risk (RR; for the risk of diabetes) with 95% confidence interval (CI) were calculated for pooled effect estimates using the random-effects model. Thirteen RCTs involving 3376 individuals with IGT or prediabetes were selected for this meta-analysis. The results showed that lifestyle interventions were associated with lower FPG (WMD: -0.14; 95% CI: -0.24 to -0.05 mmol/L; p=0.004) and 2hPPG (WMD: -0.66; 95% CI: -1.12 to -0.20 mmol/L; p=0.005) in adults with IGT or prediabetes. Moreover, the risk of diabetes was significantly reduced in individuals who received lifestyle interventions (RR: 0.75; 95% CI: 0.60-0.95; p=0.015). Lifestyle interventions could help improve glucose dysregulation and prevent the progression of diabetes in adults with IGT or prediabetes. Further large-scale RCTs should be conducted to assess the effects of long-term lifestyle interventions on diabetic complications in adults with IGT or prediabetes.

ß-Aescin shows potent antiproliferative activity in osteosarcoma cells by inducing autophagy, ROS generation and mitochondrial membrane potential loss.

PURPOSE: Osteosarcoma is one of the frequent bone tumor affecting mainly children and is associated with considerable mortality. The limited availability of anticancer drugs and less efficacious treatment options have led to poor survival rates of patients with osteosarcoma. Therefore, there is need to look for more viable treatment options and against this backdrop, natural products may prove handy. Therefore the aim of the present study was to evaluate the anticancer activity of a natural product of plant origin, ß-aescin, against U2OS human osteosarcoma cells. METHODS: U205 human osteosarcoma cell line was used in this study. Antiproliferative activity was determined by MTT assay. Reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were evaluated by flow cytometry. Autophagy was detected by monodansylcadaverine (MDC) staining and immunofluorescence. Protein expression was examined by western blotting. RESULTS: The results indicated that ß-aescin showed significant anticancer activity against U2OS human osteosarcoma cells and exhibited an IC50 of 40 µM. ß-aescin treatment caused significant increase in ROS and decrease in the MMP. The anticancer effect of ß-aescin was found to be due mainly to autophagic cell death as evidenced from MDC staining and immunofluorescence. Moreover, ß-aescin caused significant increase in the expression levels of LC3- II protein in U2OS osteosarcoma cells in a time and dosedependent manner. CONCLUSION: Taken together we propose that ß-aescin may prove a lead molecule in the management of osteosarcoma and deserves further research efforts.

Long-term outcomes of adjunctive complex fractionated electrogram ablation to pulmonary vein isolation as treatment for non-paroxysmal atrial fibrillation.

PURPOSE: The adjunctive ablation of areas of complex fractionated electrogram (CFE) to pulmonary vein isolation (PVI) is an emerging strategy for patients with non-paroxysmal atrial fibrillation (AF). We studied the long-term outcomes of this approach. METHODS: Sixty-six patients (mean age 58 ± 9, 86.4 % male) with non-paroxysmal AF underwent ablation procedures consisting of PVI plus extensive CFE ablation. Post-ablation atrial tachycardia (AT) was also targeted if presented. All patients were followed up regularly on an ambulatory basis by means of ECG and Holter recordings. RESULTS: After a mean follow-up period of 40 ± 14 months and 1.7 ± 0.7 procedures, 38 patients (57.6 %) were free of arrhythmias, 15 (22.7 %) displayed clinical improvement and 13 (19.7 %) suffered recurrences of persistent AF/AT. Females displayed poorer long-term outcomes than males (arrhythmia-free 22.2 vs. 63.2 %, p < 0.05). Multivariate analysis demonstrated that long duration of uninterrupted AF prior to the procedure was an additional predictor of long-term failure (odds ratio 1.49, p < 0.01). ROC analysis (area under curve 0.80; p < 0.001) estimated 3.5 years as the optimal cut-off point for predicting long-term failure (sensitivity 85 %, specificity 74 %). The cumulative data showed a significantly higher percentage of arrhythmia-free patients when the duration of AF had been ≤ 2 years (69.7 %) and ≤ 4 years (68.9 %) than when it was > 4 years (33.3 %; p < 0.01). CONCLUSIONS: PVI + CFE ablation in non-paroxysmal AF appears to provide a reasonable proportion of arrhythmia-free patients during long-term follow-up. Poorer long-term results can be expected among female patients and those with an uninterrupted AF duration of > 4 years.

Ablation effect indicated by impedance fall is correlated with contact force level during ablation for atrial fibrillation.

INTRODUCTION: Previous studies have validated the use of impedance fall as a measure of the effects of ablation. We investigated whether catheter-to-tissue contact force correlated with impedance fall during atrial fibrillation ablation. METHODS AND RESULTS: A total of 394 ablation points from 35 patients who underwent atrial fibrillation ablation were selected and analyzed in terms of the presence of stable catheter contact in non-ablated areas in the left atrium. A fixed power output (30 W) was applied for 60 seconds. Contact force, impedance fall, and force-direction angle were retrieved and exported for off-line analysis. Qualified points were divided into 5 groups according to the level of contact force (1-5 g, 6-10 g, 11-15 g, 16-20 g, and >20 g). An acute impedance fall was observed in the first 10 seconds followed by a plateau in group I and by a further fall in the other groups. Group V showed a rise in impedance during the last 20 seconds of ablation. Levels of impedance fall at each time point were significantly different among all the groups (P<0.001) except between groups III and IV. There was a significant correlation between contact force and maximum impedance fall (rho = 0.54, P<0.01). Lesions with a force-direction angle of 0-30° had significantly lower contact force and maximum impedance fall than those with angles of 30-60° and 60-135° (P<0.01). CONCLUSIONS: Under stable catheter conditions, contact force correlates with impedance fall during 60 seconds of ablation. Contact force exceeding 5 g produces greater impedance fall, which probably indicates adequate lesion formation. A contact force greater than 20 g may lead to late tissue overheating.

MnBa(2)(HPO(4))(2)(H(2)PO(4))(2).

Crystals of manganese(II) dibarium bis-(hydrogenphosphate) bis-(dihydrogenphosphate), MnBa(2)(HPO(4))(2)(H(2)PO(4))(2), were obtained by hydro-thermal synthesis. The title compound is isotypic with its Cd(II) and Ca(II) analogues. The structure is built up of an infinite {[Mn(HPO(4))(2)(H(2)PO(4))(2)](4-)}(n) chain running along [100], which consists of alternate MnO(6) octa-hedra and [PO(4)] tetra-hedra, in which the centrosymmetric MnO(6) octa-hedra share their four equatorial O-atom corners with tetra-hedral [PO(3)(OH)] groups and their two axial apices with tetra-hedral [PO(2)(OH)(2)] groups. These chains are held together by BaO(9) coordination polyhedra, developing into a three-dimensional structure. The O-H⋯O hydrogen bonds additionally stabilize the structural set-up. Due to the ionic radius of Mn(2+) being much smaller than those of Ca(2+) and Cd(2+), this may imply that their adopted structure type has a great tolerance for incorporating various ions and the exploitation of more diverse compounds in the future is encouraged.

Drug Adverse Reaction Target Database (DART) : proteins related to adverse drug reactions.

An adverse drug reaction (ADR) often results from interaction of a drug or its metabolites with specific protein targets important in normal cellular function. Knowledge about these targets is both important in facilitating the study of the mechanisms of ADRs and in new drug discovery. It is also useful in the development and testing of rational drug design and safety evaluation tools. The Drug Adverse Reaction Database (DART) is intended to provide comprehensive information about adverse effect targets of drugs described in the literature. Moreover, proteins involved in adverse effect targets of chemicals not yet confirmed as ADR targets are also included as potential targets. This database gives physiological function of each target, binding drugs/agonists/antagonists/activators/inhibitors, IC(50) values of the inhibitors, corresponding adverse effects, and type of ADR induced by drug binding to a target. Cross-links to other databases are also introduced to facilitate the access of information about the sequence, 3-dimensional structure, function, and nomenclature of each target along with drug/ligand binding properties, and related literature. The database currently contains entries for 147 ADR targets and 89 potential targets. A total of 187 adverse reaction conditions, 257 drugs, and 1080 ligands known to bind to each of these targets are also currently described. Each entry can be retrieved through multiple search methods including target name, target physiological function, adverse effect, ligand name, and biological pathways. A special page is provided for contribution of new or additional information. This database can be accessed at http://xin.cz3.nus.edu.sg/group/drt/dart.asp.