Project description:The BCN02 (NCT02616874) was a pilot study to evaluate the kick and kill therapy on 15 early-treated individuals that were rolled-over from the BCN01 Study. The participants in the study received two MVA.HIVconsv vaccination before and after the 3-cycle infusion of Romidepsin, an inhibitor of histone deacetylases that act as a latency reversing agent. Additionally, the inclusion of a monitored antiretroviral pause (MAP) allowed tthe identification of 8 individuals with an Early Rebound (pVL > 2,000 HIV RNA copies/mL, < 4 weeks of MAP initiation) and 4, with a Late Rebound (pVL > 2,000 HIV RNA copies/mL, > 4 weeks of MAP initiation). In the present study we studied gene expression at 3 different timepoints: w0 (Bsl), w1 (Vacc), w6 (Vacc+RMD) and applied pairwise comparisons.
Project description:Recent studies have reported that plasma levels of tricarboxylic acid (TCA) cycle metabolites and TCA cycle-related metabolite change in patients with chronic fatigue syndrome (CFS) and in healthy humans after exercise. Exogenous dietary citric acid has been reported to alleviate fatigue during daily activities and after exercise. However, it is unknown whether dietary citric acid affects the plasma levels of these metabolites. Therefore, the present study aimed to investigate the effects of exogenously administered citric acid on TCA cycle metabolites and TCA cycle-related metabolites in plasma. Sprague-Dawley rats were divided into control and citric acid groups. We evaluated the effect of exogenous dietary citric acid on the plasma TCA cycle and TCA cycle-related metabolites by metabolome analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS). TCA cycle metabolites, including plasma citrate, cis-aconitate, and isocitrate, were significantly elevated after exogenous administration of citric acid. Anaplerotic amino acids, which are converted to TCA cycle metabolites, such as serine, glycine, tryptophan, lysine, leucine, histidine, glutamine, arginine, isoleucine, methionine, valine, and phenylalanine, also showed significantly elevated levels. Citric acid administration significantly increased the levels of initial TCA cycle metabolites in the plasma. This increase after administration of citric acid was shown to be opposite to the metabolic changes observed in patients with CFS. These results contribute novel insight into the fatigue alleviation mechanism of citric acid.
Project description:AimsThe geographic representation of investigators and participants in heart failure (HF) randomized controlled trials (RCTs) may not reflect the global distribution of disease. We assessed the geographic diversity of RCT leaders and explored associations with geographic representation of enrolled participants among impactful HF RCTs.Methods and resultsWe searched MEDLINE, EMBASE, and CINAHL for HF RCTs published in journals with impact factor ≥ 10 between January 2000 and June 2020. We used the Jonckheere-Terpstra test to assess temporal trends and multivariable logistic regression models to explore associations between predictors and outcomes. There were 414 eligible RCTs. Only 80 of 828 trial leaders [9.7%; 95% confidence interval (CI): 7.8-11.8%] and 453 of 4656 collaborators (9.7%; 95% CI: 8.8-10.6%) were from outside Europe and North America, with no change in temporal trends and with greater disparities in large RCTs. The adjusted odds of trial leadership outside Europe and North America were lower with industry funding [adjusted odds ratio (aOR): 0.33; 95% CI: 0.15-0.75; P = 0.008]. Among 157 416 participants for whom geography was reported, only 14.5% (95% CI: 14.3-14.7%) were enrolled outside Europe and North America, but odds of enrolment were 10-fold greater with trial leadership outside Europe and North America (aOR: 10.0; 95% CI: 5.6-19.0; P < 0.001).ConclusionRegions disproportionately burdened with HF are under-represented in HF trial leadership, collaboration, and enrolment. RCT leadership outside Europe and North America is independently associated with participant enrolment in under-represented regions. Increasing research capacity outside Europe and North America could enhance trial diversity and generalizability.
Project description:Introduction: Exercise performance is reproducible in experienced athletes; however, less trained participants exhibit greater variability in performance and pacing. To reduce variability, it is common practice to complete a familiarization prior to experimental testing. However, there are no clear guidelines for familiarizing novice participants to a cycling time-trial (TT), and research findings from novice populations may still be influenced by learning effects. Accordingly, the aims of this study were to establish the variability between TTs after administering differing familiarization protocols (duration or type) and to establish the number of familiarization trials required to limit variability over multiple trials. Methods: Thirty recreationally active participants, with no prior experience of a TT, performed a 20-km cycling TT on five separate occasions, after completing either a full (FF, 20-km TT, n = 10), a half (HF, 10-km TT, n = 10) or an equipment familiarization (EF, 5-min cycling, n = 10). Results: Variability of TT duration across five TTs was the lowest after completing FF (P = 0.69, η p2 = 0.05) compared to HF (P = 0.08, η p2 = 0.26) and EF (P = 0.07, η p2 = 0.21). In the FF group after TT2, the effect size for changes in TT duration was small (d < 0.49). There were large differences between later TTs in HF (d = 1.02, TT3-TT4) and EF (d = 1.12, TT4-TT5). The variability in mean power output profiles between trials was lowest within FF, with a similar pacing profile reproduced between TT3-TT5. Discussion: Familiarization of the exercise protocol influenced reproducibility of pacing and performance over multiple, maximal TTs, with best results obtained after a full experience of the exercise compared to HF and EF. The difference of TT1 to later TTs indicates that one familiarization is not adequate in reducing the variability of performance for novice participants. After the FF and an additional TT, performance changes between TTs were small, however, a reproducible pacing profile was not developed until after the FF and two additional TTs. These findings indicate that a minimum of three full familiarizations are necessary for novice participants to limit systematic error before experimental testing.