Circulating microRNAs implicate multiple atherogenic abnormalities in the long-term cardiovascular sequelae of preeclampsia

Background: Women who have had preeclampsia (PE) are at increased risk for premature cardiovascular disease (CVD). The underlying pathophysiology of this risk remains unclear, but potentially involves subclinical vascular damage or dysfunction. Alterations in the levels of circulating microRNAs may be implicated, as they are known to play pervasive roles in vascular biology. We investigated whether levels of circulating microRNAs are altered between women with premature acute coronary syndrome (ACS), with and without a history of PE. Methods: Women with premature ACS (age ≤ 55 years) were categorized based on a prior history of PE or normotensive pregnancy. Relative plasma levels of 372 microRNAs were initially assessed by polymerase chain reaction array in a subset of subjects (n = 12–13/group) matched for age, chronic hypertension, dyslipidemia, and smoking status. Candidate microRNAs were then validated in a larger cohort of ACS patients (n = 176). Results: MicroRNAs previously linked to angiogenesis (miR-126-3p), inflammation (miR-146a-5p), and cholesterol metabolism (miR-122-5p) were significantly decreased in women with prior PE compared to women with prior normotensive pregnancy (P = 0.002, 0.017, and 0.009, respectively), even after adjustment for chronic hypertension. Conclusions: Circulating levels of miR-126-3p, -146a-5p, and -122-5p were significantly decreased in women with premature ACS who reported prior PE compared to those with prior normotensive pregnancy. These data provide novel insight into potential pathways that may contribute to the increased risk of CVD following PE

Circulating miR-206 and Wnt-signaling are associated with cardiovascular complications and a history of preeclampsia in women

Women with a history of preeclampsia (PE) have increased risk of cardiovascular disease (CVD) later in life. However, the molecular determinants underlying this risk remain unclear. We sought to understand how circulating miRNA levels are impacted by prior PE, and relate to biological pathways underpinning cardiovascular disease. RNA sequencing was used to profile plasma levels of 2578 miRNAs in a retrospective study of women with a history of PE or normotensive pregnancy, in two independent cohorts with either acute coronary syndrome (ACS) (n=17-18/group) or no ACS (n=20/group). Differential miRNA alterations were assessed in relation to a history of PE (within each cohort) or ACS (across cohorts), and compared to miRNAs previously reported to be altered during PE. A history of PE was associated with altered levels of 30 and 20 miRNAs in the ACS and non-ACS cohorts, respectively, whereas ACS exposure was associated with alterations in 259 miRNAs. MiR-206 was identified at the intersection of all comparisons relating to past/current PE and ACS exposure, and has previously been implicated in atherogenic activities related to hepatocytes, vascular smooth muscle cells and macrophages. Integration of all differentially altered miRNAs with their predicted and experimentally-validated targets in silico revealed a number of highly targeted genes with potential atherogenic functions (including NFAT5, CCND2 and SMAD2), and one significantly enriched KEGG biological pathway (Wnt signaling) that was shared between all exposure groups. This study provides novel insights into miRNAs, target genes and biological pathways that may underlie the long term cardiovascular sequelae of PE

Type 1 diabetes mellitus and educational attainment in childhood: a systematic review

Objectives The primary objective of this systematic review was to evaluate available literature on whether type 1 diabetes mellitus (T1DM) has an impact on educational attainment in individuals undertaking high stakes standardised testing at the end of compulsory schooling. Design A systematic review was undertaken comparing educational attainment for individuals with and without T1DM who have undertaken high stakes testing at the end of compulsory schooling. Data sources A comprehensive search of MEDLINE, MEDLINE (epub ahead of print, in-process and other non-indexed citations), EMBASE, Web of Science, British Education Index, Education Resources Information Center and Cumulative Index to Nursing and Allied Health Literature was undertaken on 15 January 2018 and updated on 17 January 2019. Eligibility criteria Included studies fulfilled the following criteria: observational study or randomised controlled trial; included individuals who have undertaken high stakes testing at the end of compulsory schooling; compared the grades obtained by individuals with T1DM with a representative population control. Data extraction and synthesis Two reviewers performed study selection and data extraction independently. Quality and risk of bias in the observational studies included were assessed using the Newcastle-Ottawa Scale. A detailed narrative synthesis of the included studies was completed. Results 3103 articles were identified from the database search, with two Swedish cohort studies (using the same linked administrative data) meeting final inclusion criteria. A small but statistically significant difference was reported in mean final grades, with children with T1DM found to have lower mean grades than their non-diabetic counterparts (adjusted mean difference 0.07–0.08). Conclusions More contemporary research is required to evaluate the impact of T1DM in childhood on educational attainment in individuals undertaking high stakes standardised testing at the end of compulsory schooling, taking into consideration the substantial advances in management of T1DM in the last decade

The association between Type 1 diabetes mellitus and educational attainment in childhood: a systematic review protocol

Introduction Type 1 diabetes has the potential to significantly impact children’s educational attainment. With the increase in incidence, quantifying this effect would be useful to assess how much additional support should be focused on children with type 1 diabetes in school. Methods and analysis We will conduct a systematic review of all observational studies and randomised controlled trials, including individuals both with and without a diagnosis of type 1 diabetes who have undertaken high stakes testing at the end of compulsory schooling when under 18 years of age. The search will cover both peer-reviewed and grey literature available from January 2004 to January 2018. The following seven databases will be searched: Ovid MEDLINE (1946 to present), Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid EMBASE (1947 to present), Thomson Reuters Web of Science, EBSCO Education Resources Information Center, EBSCO British Education Index and EBSCO Cumulative Index to Nursing and Allied Health Literature. Study selection and data extraction will be performed independently by two reviewers with any disagreements resolved via a third reviewer. The quality and risk of bias in the observational studies included in this review will be assessed using the Newcastle-Ottawa Scale. We aim to conduct a meta-analysis and will assess heterogeneity between the included studies and potential for publication bias if sufficient (>10) studies are included. Results and dissemination Formal ethical approval is not required as individual patient data will not be collected. Results will be disseminated through peer-reviewed publication and conference presentations

Turning negative into positives! Exploiting ‘negative’ results in Brain–Machine Interface (BMI) research

Results that do not confirm expectations are generally referred to as ‘negative’ results. While essential for scientific progress, they are too rarely reported in the literature – Brain–Machine Interface (BMI) research is no exception. This led us to organize a workshop on BMI negative results during the 2018 International BCI meeting. The outcomes of this workshop are reported herein. First, we demonstrate why (valid) negative results are useful, and even necessary for BMIs. These results can be used to confirm or disprove current BMI knowledge, or to refine current theories. Second, we provide concrete examples of such useful negative results, including the limits in BMI-control for complete locked-in users and predictors of motor imagery BMI performances. Finally, we suggest levers to promote the diffusion of (valid) BMI negative results, e.g. promoting hypothesis-driven research using valid statistical tools, organizing special issues dedicated to BMI negative results, or convincing institutions and editors that negative results are valuable

A review of rapid serial visual presentation-based brain-computer interfaces

International audienceRapid serial visual presentation (RSVP) combined with the detection of event related brain responses facilitates the selection of relevant information contained in a stream of images presented rapidly to a human. Event related potentials (ERPs) measured non-invasively with electroencephalography (EEG) can be associated with infrequent targets amongst a stream of images. Human-machine symbiosis may be augmented by enabling human interaction with a computer, without overt movement, and/or enable optimization of image/information sorting processes involving humans. Features of the human visual system impact on the success of the RSVP paradigm, but pre-attentive processing supports the identification of target information post presentation of the information by assessing the co-occurrence or time-locked EEG potentials. This paper presents a comprehensive review and evaluation of the limited but significant literature on research in RSVP-based brain-computer interfaces (BCIs). Applications that use RSVP-based BCIs are categorized based on display mode and protocol design, whilst a range of factors influencing ERP evocation and detection are analyzed. Guidelines for using the RSVP-based BCI paradigms are recommended, with a view to further standardizing methods and enhancing the inter-relatability of experimental design to support future research and the use of RSVP-based BCIs in practice

Antigen-specific immunotherapy with thyrotropin receptor peptides in Grave's Hyperthyroidism: a Phase I study

Graves' disease is one of the most common autoimmune conditions, but treatment remains imperfect. This study explores the first-in-human use of antigen-specific immunotherapy with a combination of two thyrotropin receptor (TSHR) peptides (termed ATX-GD-59) in Graves' hyperthyroidism.This article is freely available via Open Access. Click on the Publisher's URL to access the full-text via the publisher's site.Publishe

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat