Methodological Quality and Risk of Bias Assessment of Cardiovascular Disease Research: Analysis of Randomized Controlled Trials Published in 2017

BACKGROUND: All randomized-controlled trials (RCTs) are required to follow high methodological standards. In this study, we aimed to assess the methodological quality of published cardiovascular clinical research trials in a representative sample of RCTs published in 2017. METHODS: Cochrane Central Register of Controlled Trials was used to identify cardiovascular clinical research trials with adult participants published in 2017. Overall, 250 (10%) RCTs were randomly selected from a total of 2,419 studies. Data on general trial characteristics were extracted and the risk of bias (RoB) was determined. RESULTS: Overall, 86% of RCTs have reported at least one statistically significant result, with the primary outcome significant in 69%, treatment favored in 55%, and adverse events reported in 68%. Less than one-third (29%) of trials were overall low RoB, while the other two-thirds were rated unclear (40%) or with high RoB (31%). Sequence generation, allocation concealment, and selective reporting were the domains most often rated with high RoB. Drug trials were more likely to have low RoB than non-drug trials. Significant differences were found in RoB for the allocation concealment and blinding of participants and personnel between industry-funded and non-industry-funded trials, with industry-funded trials more often rated at low RoB. CONCLUSION: Almost two-thirds of RCTs in the field of cardiovascular disease (CVD) research, were at high or unclear RoB, indicating a need for more rigorous trial planning and conduct. Prospective trial registration is a factor predicting a lower risk of bias

The more we do, the less we gain? Balancing effort and efficacy in managing the Solidago gigantea invasion

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CD8+ and CD8- NKT Cells Exhibit Phenotypic Changes During Pregnancy

Background: NKT cell population is a relatively well-characterized immune cell subset. Numerous publications have characterized the phenotypical features of its subpopulations even in human pregnancy. Nevertheless, there have not been studies investigating the distribution of the NKT cells based on the surface presence of the CD8 receptor. Methods: Thirty-four pregnant women from the first trimester, 30 from the second, and 36 from the third trimester of pregnancy in addition to 35 healthy non-pregnant women have been involved in the study. PBMCs were isolated from peripheral blood, CD8+ and CD8-NKT cells were then studied by flow cytometry using monoclonal antibodies. Immune checkpoint molecules and intracellular markers were also measured. Results: Substantial differences were revealed in the proportions of the NKT cell subpopulations in the healthy control cohort and the pregnant groups. By comparing the investigated groups, significant changes were detected in the expression levels of PD-L1, TIGIT, CD155, and NKG2D. Further associations were observed through examination of the relative expressions of TIGIT and CD226 in the CD8+ NKT subset. Conclusion: Data suggest that the CD8+ NKT cells are under fine regulation during healthy human pregnancy

Examination of the TIGIT-CD226-CD112-CD155 Immune Checkpoint Network During a Healthy Pregnancy

Background: The importance of immune checkpoint molecules is well known in tumor and transplantation immunology; however, much less information is available regarding human pregnancy. Despite the significant amount of information about the TIGIT and CD226 immune checkpoint receptors in immune therapies, very little research has been conducted to study the possible role of these surface molecules and their ligands (CD112 and CD155) during the three trimesters of pregnancy. Methods: From peripheral blood, immune cell subpopulations were studied, and the surface expression of immune checkpoint molecules was analyzed by flow cytometry. Soluble immune checkpoint molecule levels were measured by ELISA. Results: Notable changes were observed regarding the percentage of monocyte subpopulation and the expression of CD226 receptor by CD4+ T and NKT cells. Elevated granzyme B content by the intermediate and non-classical monocytes was assessed as pregnancy proceeded. Furthermore, we revealed an important relationship between the CD226 surface expression by NKT cells and the serum CD226 level in the third trimester of pregnancy. Conclusions: Our results confirm the importance of immune checkpoint molecules in immunoregulation during pregnancy. CD226 seems to be a significant regulator, especially in the case of CD4+ T and NKT cells, contributing to the maternal immune tolerance in the late phase of pregnancy

Change over five years in important measures of methodological quality and reporting in randomized cardiovascular clinical trials

Objectives: The aim of our current study was to analyze whether the use of important measures of methodological quality and reporting of randomized clinical trials published in the field of cardiovascular disease research haschanged over time. A furtheraim was to investigate whether there was an improvement over time in the ability of these trials to provide a good estimate of the true intervention effect. Methods: We conducted two searches in the Cochrane Central Register of Controlled Trials (CENTAL) database to identify randomized cardiovascular clinical trials published in either 2012 or 2017. Randomized clinical trials (RCTs) trials in cardiovascular disease research with adult participants were eligible to be included. We randomly selected 250 RCTs for publication years 2012 and 2017. Trial characteristics, data on measures of methodological quality, and reporting were extracted and the risk of bias for each trial was assessed. Results: As compared to 2012, in 2017 there were significant improvements in the reporting of the presence of a data monitoring committee (42.0% in 2017 compared to 34.4% in 2012; p < 0.001), and a positive change in registering randomized cardiovascular disease research in clinical trial registries (78.4% in 2017 compared to 68.9% in 2012; p = 0.03). We also observed that significantly more RCTs reported sample size calculation (60.4% in 2017 compared to 49.6% in 2012; p < 0.01) in 2017 as compared to 2012. RCTs in 2017 were more likely to have a low overall risk of bias (RoB) than in 2012 (29.2% in 2017 compared to 21.2% in 2012; p < 0.01). However, fewer 2017 RCTs were rated low (50.8% compared to 65.6%; p < 0.001) risk for blinding of participants and personnel, for blinding of outcome assessors (82.4% compared to 90.8%; p < 0.001), and selective outcome reporting (62.8% compared to 80.0%; <0.001). Conclusions: As compared to 2012, in 2017 there were significant improvements in some, but not all, the important measures of methodological quality. Although more trials in the field of cardiovascular disease research had a lower overall RoB in 2017, the improvement over time was not consistently perceived in all RoB domains

A Modeling Approach to Studying the Influence of Grafting on the Anatomical Features and <i>SAUR</i> Gene Expression in Watermelons

Grafting alters the genetic and anatomical features of plants. Although grafting has been widely applied in plant propagation, the underlying processes that govern the effects of the procedure are not fully understood. Samples were collected to study the long-term influence of grafting on the leaf-shoot morphology, leaf-shoot anatomy, and genetic signature of the grafted plants. Citrulus lanatus (Thunb.) Matsum. & Nakai (cv. Lady) was used as the scion, and Lagenaria siceraria (Molina) Standl (cv. Argentario) as a rootstock. In grafted plants, leaf blades and petioles were 20.92% and 12.82% longer, respectively, while the midrib collenchyma was 35.68% thicker, and the diameter of the vessel member was 11.17% larger than in ungrafted plants. In the stem, grafting affected the arrangement and number of vascular bundles (from 1 to 2 rings). The thickness of the epidermis decreased by 69.79%, and the size of the external fascicular phloem decreased by 23.56%. The diameter of the vessel member of the grafted plants increased by 28.94%. Eight out of ten evaluated primers met the requirements (stability in both watermelons and bottle gourd, tissue-specific). In the genetic tests, we examined whether this change in the gene expression pattern is due to the grafting and, if so, to what extent. Seven out of eight tested Small Auxin Up-Regulated RNA (SAUR) genes were expressed in the ungrafted and grafted C. lanatus lines in four cases; the expression increased by more than 10% after grafting. The morpho-anatomical changes and genetic variation reported in this study for grafted lines of C. lanatus contribute to the understanding of the underlying mechanisms of plant growth observations resulting from grafting

Flowering phenophases influence the antibacterial and anti-biofilm effects of Thymus vulgaris L. essential oil

Abstract Background Essential oils are becoming increasingly popular in medicinal applications because of their antimicrobial effect. Thymus vulgaris L. (Lamiaceae) is a well-known and widely cultivated medicinal plant, which is used as a remedy for cold, cough and gastrointestinal symptoms. Essential oil content of thyme is responsible for its antimicrobial activity, however, it has been reported that the chemical composition of essential oils influences its biological activity. In order to explore flowering phenophases influence on the chemical composition of thyme essential oil and its antibacterial and anti-biofilm activity, plant materials were collected at the beginning of flowering, in full bloom and at the end of flowering periods in 2019. Methods Essential oils from fresh and dried plant materials were distilled and analyzed with gas chromatography-mass spectrometry (GC-MS) and gas chromatography-flame ionization detection (GC-FID). The antibacterial activity was performed by broth microdilution and thin layer chromatography-direct bioautography (TLC-DB) assays and the anti-biofilm effect by crystal violet assay, respectively. Scanning electron microscopy was applied to illustrate the cellular changes of bacterial cells after essential oil treatment. Results Thymol (52.33–62.46%) was the main component in the thyme essential oils. Thyme oil distilled from fresh plant material and collected at the beginning of flowering period exerted the highest antibacterial and anti-biofilm activity against Haemophilus influenzae, H. parainfluenzae and Pseudomonas aeruginosa. Conclusion The different flowering periods of Thymus vulgaris influence the antibacterial and anti-biofilm activity of its essential oils, therefore, the collection time has to be taken into consideration and not only the full bloom, but the beginning of flowering period may provide biological active thyme essential oil