scholarly journals Meta-analysis of metabolites involved in bioenergetic pathways reveals a pseudohypoxic state in Down syndrome

2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Laszlo Pecze ◽  
Elisa B. Randi ◽  
Csaba Szabo
Keyword(s):  
Down Syndrome ◽  
Meta Analysis ◽  
Experimental Therapy ◽  
Mixed Effect ◽  
Functional Deficits ◽  
Clinical Observations ◽  
Effect Model ◽  
Acid Succinate ◽  
The Difference ◽  
And Control

Abstract Clinical observations and preclinical studies both suggest that Down syndrome (DS) may be associated with significant metabolic and bioenergetic alterations. However, the relevant scientific literature has not yet been systematically reviewed. The aim of the current study was to conduct a meta-analysis of metabolites involved in bioenergetics pathways in DS to conclusively determine the difference between DS and control subjects. We discuss these findings and their potential relevance in the context of pathogenesis and experimental therapy of DS. Articles published before July 1, 2020, were identified by using the search terms “Down syndrome” and “metabolite name” or “trisomy 21” and “metabolite name”. Moreover, DS-related metabolomics studies and bioenergetics literature were also reviewed. 41 published reports and associated databases were identified, from which the descriptive information and the relevant metabolomic parameters were extracted and analyzed. Mixed effect model revealed the following changes in DS: significantly decreased ATP, CoQ10, homocysteine, serine, arginine and tyrosine; slightly decreased ADP; significantly increased uric acid, succinate, lactate and cysteine; slightly increased phosphate, pyruvate and citrate. However, the concentrations of AMP, 2,3-diphosphoglycerate, glucose, and glutamine were comparable in the DS vs. control populations. We conclude that cells of subjects with DS are in a pseudo-hypoxic state: the cellular metabolic and bio-energetic mechanisms exhibit pathophysiological alterations that resemble the cellular responses associated with hypoxia, even though the supply of the cells with oxygen is not disrupted. This fundamental alteration may be, at least in part, responsible for a variety of functional deficits associated with DS, including reduced exercise difference, impaired neurocognitive status and neurodegeneration.

scholarly journals Effects of Diet, Aerobic Exercise, or Both on Non-HDL-C in Adults: A Meta-Analysis of Randomized Controlled Trials

Cholesterol ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
George A. Kelley ◽  
Kristi S. Kelley
Keyword(s):  
Aerobic Exercise ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Density Lipoprotein ◽  
Control Group ◽  
Controlled Trials ◽  
Mixed Effect ◽  
Randomized Controlled ◽  
Effect Model

Purpose. To use the meta-analytic approach to examine the effects of diet (D), aerobic exercise (E), or both (DE) on non-high-density lipoprotein cholesterol (non-HDL-C) in adults. Methods. Randomized controlled trials in adults ≥18 years of age were included. A mixed-effect model was used to combine effect size (ES) results within each subgroup and to compare subgroups (Qb). Heterogeneity was examined using the Q and I2 statistics, and 95% confidence intervals (CI) were also calculated. Statistical significance was set at P≤0.05, while a trend for statistical significance was set between P>0.05, and ≤0.10. Results. A statistically significant exercise minus control group decrease in non-HDL-C was found for DE (7 ESs, 389 participants, x¯=-11.1 mg/dL, 95%  CI=−21.7 to −0.6, P=0.04, Q=2.4, P=0.88, I2=0%), a trend for the D group (7 ESs, 402 participants, x¯=−8.5 mg/dL, 95%  CI=−18.6 to 1.6, P=0.10, Q=0.76, P=0.99, I2=0%), and no change for the E group (7 ESs, 387 participants, x¯=3.0 mg/dL, 95%   CI=−7.1 to 13.1, P=0.56, Q=0.78, P=0.99, I2=0%). Overall, no statistically significant between-group differences were found (Qb=4.1, P=0.12). Conclusions. Diet combined with aerobic exercise may reduce non-HDL-C among adults in some settings.

Abstract 240: Serum Cholesterol and Angiotensin-Induced Abdominal Aortic Aneurysm in Hypercholesterolemic Mice

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Petra A Prins ◽  
Michael Hill ◽  
David Airey ◽  
Sam Nwosu ◽  
Prudhvidhar R Perati ◽  
...  
Keyword(s):  
Aortic Aneurysms ◽  
Cholesterol Concentration ◽  
Linear Mixed Effect Model ◽  
Hemodynamic Parameters ◽  
Mixed Effect ◽  
Regression Methods ◽  
Effect Model ◽  
Abdominal Aortic ◽  
And Control ◽  
The Relationship

Background Although hyperlipidemia is known to augment the incidence of abdominal aortic aneurysms (AAA) in the AngII-induced model of apolipoprotein E -/- mice, its relationship to AAA size is unknown. Therefore, we evaluated the relationship between total cholesterol concentration (TC) and change (delta) in aortic diameter. Methods TC was measured in 36 male mice that underwent a 4-week infusion period with saline (n=9) or AngII (1500 ng/kg/min; n=27), along with serial measurements of pulse rate (PR), and pulse (PP), mean arterial (MAP), systolic (SBP) and diastolic (DBP) pressure. A linear mixed effect model was used to assess the relationship between all hemodynamic parameters and delta. Nonparametric and linear regression methods were used to evaluate TC in relation to delta. Results TC did not differ between AngII and control mice (Figure, bottom left) (p=0.18). The burden of atherosclerosis was greater among AngII-exposed mice versus control, but did not differ by presence or size of AAA (Figure, bottom right). None of the hemodynamic parameters were predictive of delta (SBP, p = 0.66; DBP, p = 0.66; MAP, p = 0.55; PP, p = 0.66; and PR, p = 0.39). Mean TC was higher among mice with large versus small AAA (552.6 vs. 393.5 mg/ ml, p<0.05; Figure, top right). The nonparametric smoothing line (Figure, top left) suggests a first order relationship between delta and TC (p for trend < 0.001). AngII (ß = 0.48, p < 0.001) and TC (ß = 0.0015, p = 0.003) were independent predictors in the linear model for delta. Conclusions Our findings suggest that TC is incrementally associated with AAA size. These findings may have potential clinical relevance for risk assessment in AAA patients. Figure

Abstract 2211: Statin Therapy May Increase the Risk of Intracerebral Hemorrhage: A Meta-analysis of 26 Randomized Controlled Trials

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
James S McKinney ◽  
William J Kostis ◽  
John B Kostis
Keyword(s):  
Statin Therapy ◽  
Meta Analysis ◽  
Active Group ◽  
Controlled Trials ◽  
Control Groups ◽  
Randomized Controlled ◽  
All Cause Mortality ◽  
Group A ◽  
The Difference ◽  
And Control

Introduction--- Statin therapy decreases the risk of myocardial infarction and ischemic stroke. However, an increased risk of intracerebral hemorrhage (ICH) has been observed in some studies. To investigate this issue we performed a meta-analysis of all randomized controlled trials (RCTs) using statins that reported ICH. Methods--- We performed a Medline literature search through March 18, 2011 and identified additional RCTs by reviewing reference lists of retrieved studies and prior meta-analyses. All RCTs of statin therapy versus placebo or high dose versus low dose statin therapy that reported ICH or hemorrhagic stroke were included. The primary outcome variable was ICH. 26 RCTs were included. All analyses used random effects models and heterogeneity was not observed in any of the analyses. Results--- 84 831 subjects were included in the Active group, and 84 851 in the Control group. A trend towards a higher incidence of ICH was observed in the Active treatment group compared to Control (OR = 1.15; 95% CI = 0.91 to 1.45, p =0.24) (Figure). Significant relationships were not observed between the log OR for ICH with achieved LDL in the Active group (slope = 0.0002; 95% CI = -0.0098 to 0.0101, p =0.96) or with the difference in LDL drop between the Active and Control groups (slope = 0.0030; 95% CI = -0.0089 to 0.0149, p =0.62). Total stroke (OR = 0.84; 95% CI = 0.78 to 0.91, p <0.001) and all-cause mortality (OR = 0.91; 95% CI = 0.86 to 0.96, p <0.001) were significantly reduced in the Active group. A significant relationship between all-cause mortality and the difference in LDL drop between the Active and Control groups was observed (slope = -0.0030; 95% CI = -0.0009 to -0.0051, p<0.005). There was not evidence of publication bias in this meta-analysis. Conclusions--- Active therapy was associated with a trend towards increased ICH in this meta-analysis of 26 RCTs of statin therapy. However, this risk does not appear to be related to the degree of decline or achieved LDL. The risk of ICH is offset by a significant reduction in ischemic stroke and all-cause mortality and should not dissuade practitioners from prescribing statins in otherwise appropriate patients.

P2482Sex-based differences in cardioprotective role of SGLT-2 inhibitors in patients with type 2 diabetes mellitus

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
N Madan ◽  
S Sohal ◽  
B Parapid ◽  
L Sperling ◽  
J L Januzzi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Meta Analysis ◽  
Mixed Effect ◽  
Pooled Data ◽  
Major Cardiovascular Events ◽  
Effect Model

Abstract Background Randomized studies have shown that sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce major cardiovascular events in patients with type 2 diabetes mellitus. However, it is not known whether there are significant sex-based differences in the cardioprotective role of SGLT-2 inhibitors. Purpose To investigate whether sex differences exist in reduction of major cardiovascular events (MACE)in patients with type 2 diabetes mellitus when treated with SGLT2i. Methods A comprehensive PubMed search was conducted using keywords, (“Diabetes” AND (“Dapagliflozin” OR “Empagliflozin” OR “Canagliflozin” OR “Ertugliflozin”) AND “Outcomes”) that resulted in a total of 221 studies. Studies were included in our meta-analysis if they were randomized controlled trials, placebo-controlled, reported MACE as the primary outcome and reported sex-based subgroup analyses of these outcomes. Only 2 RCTs (EMPA-REG and DECLARE-TIMI 58) met our inclusion criteria.The sex-based event data for both trials was pooled to calculate risk ratios (RR) with 95% confidence intervals (CI). Analyses was performed using Comprehensive Meta-analysis (CMA) software. Fixed effect models, random effect models and mixed effect models were used. Results Pooled datafrom the 2 RCTs (EMPA-REG and DECLARE-TIMI 58) resulted in a total of 24,180 patients who were included in our primary analysis. Of these, 2331 patients were reported to have MACE. In our pooled data, SGLT2i reduced MACE in patients with diabetes with an overall risk ratio of 0.92 (0.85–0.99), p=0.03 (I2=0, p=0.31)using fixed effect model (Table 1). We also performed subgroup analysis of the pooled data categorizing by sex and using mixed effect model. Our subgroup analysis by sex showed a Q statistic of 1.88 with p-value of 0.17 suggesting that there is no significant difference in MACE reduction between men and women with diabetes when treated with SGLT2i. However, on further analyzing the sex differences in the individual trials, we found that women may have greater reduction in MACE compared with their male counterparts (RR in females: 0.66 (0.42–1.04); RR in males: 0.92 (0.84–1.00)), however this finding did not meet statistical significance (Table 2). Conclusion Our meta-analysis included the pooled data from 2 major RCTs (EMPA-REG and DECLARE-TIMI 58) assessing the cardioprotective role of SGLT2i in diabetic patients and shows that SGLT2i significantly reduce the risk of major adverse CV events in patients with type 2 diabetes mellitus. However, we did not find any significant sex-based differences in reduction of MACE between men and women with diabetes when treated with SGLT2i.

scholarly journals Nephroprotective Effect of Mesenchymal Stem Cells in Therapy of Kidney Disease Induced by Toxicant

2020 ◽  
Author(s):  
Shujun Lin ◽  
Wenshan Lin ◽  
Chunling Liao ◽  
Tianbiao Zhou
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Treatment Group ◽  
Kidney Disease ◽  
Drug Toxicity ◽  
Meta Analysis ◽  
Control Group ◽  
The Difference ◽  
And Control ◽  
Nephroprotective Effect

Abstract Background: Renal damage caused by drug toxicity is becoming more and more common in clinic. How to avoid and treat kidney damage caused by drug toxicity is essential to maintain patient health and reduce social economic burden. In this study, we performed a meta-analysis to assess the nephroprotective effect of mesenchymal stem cells (MSCs) in therapy of kidney disease induced by toxicant. Methods: Cochrane Library, Embase, ISI Web of Science and PubMed databases were searched up to Dec 31, 2019 to identify the studies and extract the data to assess the efficacy of MSCs for kidney disease induced by toxicant using Cochrane Review Manager Version 5.3. 27 studies were eligible and recruited for this meta-analysis. Results: The results showed that the difference of Scr between MSCs treatment group and control group was notable for 2 days, 4 days, 5 days, 6-8 days, 10-15 days, ≥42 days (2 days: WMD =-0.88, 95%CI: -1.34, -0.42, P=0.0002; 4 days: WMD=-0.69, 95%CI: -0.99, -0.39, P<0.00001; 5 days: WMD=-0.46, 95%CI: -0.67, -0.25, P<0.0001; 6-8 days: WMD=-0.51, 95%CI: -0.79, -0.22, P=0.0005; 10-15 days: WMD =-0.38, 95%CI: -0.56, -0.20, P<0.0001; ≥42 days: WMD =-0.22, 95%CI: -0.39, -0.06, P=0.007). Furthermore, the difference of BUN between MSCs treatment group and control group was notable for 2-3 days, 4-5 days, 6-8 days, ≥28 days. The results also indicated that MSCs treatment can alleviate the inflammatory cells, necrotic tubule, regenerative tubules, renal interstitial fibrosis in kidney disease induced by toxicant. Conclusion: MSCs might be a promising therapeutic agent for kidney disease induced by toxicant.

scholarly journals Effectiveness of Psychobehavioral Interventions for Female Sexual Dysfunctions: A Meta-Analysis

2016 ◽  
Vol 9 (1) ◽  
pp. 76-76
Author(s):  
A. Gunst ◽  
◽  
D. Ventus ◽  
J. Antfolk ◽  
A. Kärnä ◽  
...  
Keyword(s):  
Literature Search ◽  
Randomized Clinical Trials ◽  
Reference Lists ◽  
Meta Analysis ◽  
Control Group ◽  
Sexual Dysfunctions ◽  
Treatment Interventions ◽  
Calculated Effect ◽  
The Difference ◽  
And Control

Objective: Female sexual dysfunctions (FSDs; difficulties related to sexual desire, arousal, orgasm, and pain) are prevalent and associated with both relationship quality and overall wellbeing. Psychobehavioral interventions are widely used to treat FSDs; however, little is known about the effectiveness of these interventions. Our objective was to conduct a meta-analysis on existing randomized clinical trials of psychobehavioral treatment interventions for FSDs. Design and Method: We used the electronic databases PubMed and PsycINFO in the search of relevant studies. One researcher conducted the literature search in June 2015. The search yielded 1235 hits in PubMed and 789 hits in PsycINFO. Abstract and/or title analysis reduced the possibly relevant studies to 104. A review of the reference lists in these studies was subsequently carried out. Data of interest were coded by one researcher. In order to evaluate the accuracy of the coding, an interrater reliability test was carried out on a randomly selected part of the data. Before analyzing, another search was carried out in order to find studies published after the original literature search. Results: We calculated effect sizes expressing the difference between treatment and control group scores. At present, data analyses are still in progress. Conclusions: This is, to our knowledge, the first meta-analysis of psychobehavioral treatment for FSDs that includes more recent studies, published after 2009.

scholarly journals The impacts of hydropower on freshwater macroinvertebrate richness: A global meta-analysis

2021 ◽  
Author(s):  
Gabrielle Trottier ◽  
Katrine Turgeon ◽  
Daniel Boisclair ◽  
Cécile Bulle ◽  
Manuele Margni
Keyword(s):  
Variance Estimation ◽  
Meta Analysis ◽  
Effect Sizes ◽  
Hydroelectric Dams ◽  
Freshwater Biodiversity ◽  
Mixed Effect ◽  
Large Variability ◽  
Effect Model ◽  
Hydropower Dams ◽  
Study Designs

AbstractHydroelectric dams and their reservoirs have been suggested to affect freshwater biodiversity. However, studies investigating the consequences of hydroelectric dams and reservoirs on macroinvertebrate richness have reached opposite conclusions. We carried out a meta-analysis devised to elucidate the effects of hydropower dams and their reservoirs on macroinvertebrates richness while accounting for the potential role played by moderators such as biomes, impact types, study designs, sampling seasons and gears. We used a random and mixed effect model, combined with robust variance estimation, to conduct the meta-analysis on 72 pairs of observations (i.e., impacted versus reference) extracted from 17 studies (more than one observation per study). We observed a large range of effect sizes, from very negative to very positive impacts of hydropower. However, according to this meta-analysis, hydropower dams and their reservoirs did not have an overall clear, directional and statistically significant effect on macroinvertebrate richness. We tried to account for the large variability in effect sizes using moderators, but none of the moderators included in the meta-analysis had statistically significant effect. This suggests that some other moderators, which were unavailable for the 17 studies included in this meta-analysis, might be important (e.g., temperature, granulometry, wave disturbance and macrophytes) and that macroinvertebrate richness may be driven by local, smaller scale processes. As new studies become available, it would be interesting to keep enriching this meta-analysis, as well as collecting local habitat variables, to see if we could finally draw statistically significant conclusions about the impacts of hydropower on macroinvertebrate richness.

scholarly journals A Comparison of the Effects of Foam Rolling and Stretching on Physical Performance. A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Andreas Konrad ◽  
Markus Tilp ◽  
Masatoshi Nakamura
Keyword(s):  
Range Of Motion ◽  
Meta Analysis ◽  
Random Effect ◽  
Performance Parameters ◽  
Mixed Effect ◽  
Acute Bout ◽  
Warm Up ◽  
Foam Rolling ◽  
Effect Model ◽  
Subgroup Analyses

Foam rolling and stretching with its various techniques are frequently used as a warm-up routine to increase the range of motion of a joint. While the magnitude of the changes in range of motion between foam rolling and stretching (static and dynamic techniques) is similar, it is not clear if this also holds true for performance parameters (e.g., strength, jump height). The purpose of this meta-analysis was to compare the effects of an acute bout of foam rolling (with and without vibration) with an acute bout of stretching (with all techniques included) on performance parameters in healthy participants. We assessed the results from 13 studies and 35 effect sizes by applying a random-effect meta-analysis. Moreover, by applying a mixed-effect model, we performed subgroup analyses with the stretching technique, type of foam rolling, tested muscle, treatment duration, and type of task. We found no significant overall effect, and the analysis revealed only a trend of the performance parameters in favor of foam rolling when compared to stretching (when considering all techniques). Significantly favorable effects of foam rolling on performance were detected with subgroup analyses when compared to static stretching, when applied to some muscles (e.g., quadriceps) or some tasks (e.g., strength), when applied for longer than 60 s, or when the foam rolling included vibration. When foam rolling was compared to dynamic stretching or applied in the non-vibration mode, the same magnitude of effect was observed. While the present meta-analysis revealed no significantly different effect between foam rolling and stretching (including all techniques) prior to exercise, differences could be observed under specific conditions.

scholarly journals Could the methylation of RASSF1A be the potential epigenetic biomarker for nasopharyngeal carcinoma? – Systematic review and meta-analysis

2020 ◽  
Author(s):  
Thuan Duc Lao ◽  
Hue Hong Thieu ◽  
Dung Huu Nguyen ◽  
Thuy Ai Huyen Le
Keyword(s):  
Meta Analysis ◽  
Suppressor Gene ◽  
Test Method ◽  
Control Group ◽  
Case Group ◽  
Gene Methylation ◽  
Early Screening ◽  
Effect Model ◽  
Epigenetic Biomarker ◽  
And Control

Abstract Background: RASSF1A is a tumor suppressor gene. The methylation of RASSF1A has been reported to be associated with the nasopharyngeal tumorigenesis. However, the heterogeneity was high among different studies. This meta-analysis aimed to evaluate the value of RASSF1A methylation for diagnosing and early screening NPC. Methods: Relevant articles were identified by searching MEDLINE database. The frequency and Odds ratio (OR) were applied to estimate the effect of CDH-1 methylation based on random-/fix-effect models. A meta-analysis was performed by using MedCalc® software. The subgroup analyses were performed by test-method, ethnicity, source of NPC samples to determine likely sources of heterogeneity. Results: Total of 16 studies, included 1,548 samples: 1,095 samples from NPC samples, and 453 from non-cancerous samples, were enrolled in the meta-analysis. The overall frequency of RASSF1A methylation were 59.22% and 1.72% in case-group and control-group, respectively. By removing the poor relative studies, the heterogeneity was not observed among included studies. The association between the RASSF1A gene methylation and risk of NPC was also confirmed by calculating OR value of 37.74 (95%OR = 20.07-70.98) in fix-effect model (Q = 13.56, p = 0.48, I2 = 0.00, 95% CI = 0.00-52.19). Additionally, the significant association was also found between the methylation of RASSF1A gene and subgroups. Conclusion: This was the first meta-analysis provided scientific evidences to suggest the RASSF1A methylation was the potential diagnosis, prognosis and early screening biomarker for NPC.

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