Rheumatoid arthritis is a common autoimmune disorder influenced by both genetic and environmental factors. Epigenome-wide association studies can identify environmentally mediated epigenetic changes ...such as altered DNA methylation, which may also be influenced by genetic factors. To investigate possible contributions of DNA methylation to the aetiology of rheumatoid arthritis with minimum confounding genetic heterogeneity, we investigated genome-wide DNA methylation in disease-discordant monozygotic twin pairs.
Genome-wide DNA methylation was assessed in 79 monozygotic twin pairs discordant for rheumatoid arthritis using the HumanMethylation450 BeadChip array (Illumina). Discordant twins were tested for both differential DNA methylation and methylation variability between rheumatoid arthritis and healthy twins. The methylation variability signature was then compared with methylation variants from studies of other autoimmune diseases and with an independent healthy population.
We have identified a differentially variable DNA methylation signature that suggests multiple stress response pathways may be involved in the aetiology of the disease. This methylation variability signature also highlighted potential epigenetic disruption of multiple RUNX3 transcription factor binding sites as being associated with disease development. Comparison with previously performed epigenome-wide association studies of rheumatoid arthritis and type 1 diabetes identified shared pathways for autoimmune disorders, suggesting that epigenetics plays a role in autoimmunity and offering the possibility of identifying new targets for intervention.
Through genome-wide analysis of DNA methylation in disease-discordant monozygotic twins, we have identified a differentially variable DNA methylation signature, in the absence of differential methylation in rheumatoid arthritis. This finding supports the importance of epigenetic variability as an emerging component in autoimmune disorders.
Severe maternal morbidity: screening and review Kilpatrick, Sarah K., MD, PhD; Ecker, Jeffrey L., MD; Callaghan, William M., MD
American journal of obstetrics and gynecology,
09/2016, Letnik:
215, Številka:
3
Journal Article
Recenzirano
Odprti dostop
This document builds upon recommendations from peer organizations and outlines a process for identifying maternal cases that should be reviewed. Severe maternal morbidity is associated with a high ...rate of preventability, similar to that of maternal mortality. It also can be considered a near miss for maternal mortality because without identification and treatment, in some cases, these conditions would lead to maternal death. Identifying severe morbidity is, therefore, important, for preventing such injuries that lead to mortality and for highlighting opportunities to avoid repeat injuries. The two-step screen and review process described in this document is intended to efficiently detect severe maternal morbidity in women and to ensure that each case undergoes a review to determine whether there were opportunities for improvement in care. Like cases of maternal mortality, cases of severe maternal morbidity merit quality review. In the absence of consensus on a comprehensive list of conditions that represent severe maternal morbidity, institutions and systems should either adopt an existing screening criteria, such as having received 4 or more units of blood or having been admitted to an ICU, or create their own list of outcomes that merit review.
Background Resistance to carbapenems among Acinetobacter baumannii and Klebsiella pneumoniae presents a serious therapeutic and infection control challenge. We describe the epidemiology and genetic ...basis of carbapenem resistance in A. baumannii and K. pneumoniae in a six-hospital healthcare system in Northeast Ohio. Methods Clinical isolates of A. baumannii and K. pneumoniae distributed across the healthcare system were collected from April 2007 to April 2008. Antimicrobial susceptibility testing was performed followed by molecular analysis of carbapenemase genes. Genetic relatedness of isolates was established with repetitive sequence-based PCR (rep-PCR), multilocus PCR followed by electrospray ionization mass spectrometry (PCR/ESI-MS) and PFGE. Clinical characteristics and outcomes of patients were reviewed. Results Among 39 isolates of A. baumannii, two predominant genotypes related to European clone II were found. Eighteen isolates contained blaOXA-23, and four isolates possessed blaOXA-24/40. Among 29 K. pneumoniae isolates with decreased susceptibility to carbapenems, two distinct genotypes containing blaKPC-2 or blaKPC-3 were found. Patients with carbapenem-resistant A. baumannii and K. pneumoniae were elderly, possessed multiple co-morbidities, were frequently admitted from and discharged to post-acute care facilities, and experienced prolonged hospital stays (up to 25 days) with a high mortality rate (up to 35%). Conclusion In this outbreak of carbapenem-resistant A. baumannii and K. pneumoniae across a healthcare system, we illustrate the important role post-acute care facilities play in the dissemination of multidrug-resistant phenotypes.
Background Hospital readmissions are costly, frequent, and increasingly under public scrutiny. With increased financial constraints on the medical environment, understanding the drivers of ...unscheduled readmissions following gynecologic surgery will become increasingly important to value-driven care. Objective The current study was conducted to identify risk factors for 30-day readmission following hysterectomy for benign and malignant indications. Study Design A retrospective cohort study was conducted from 2008 through 2010 of all nongravid hysterectomies at a single tertiary care academic medical center. Clinical, perioperative, and physician characteristics were collected. Multivariable logistic regression models were used to identify predictors of 30-day readmission, stratified by malignant and benign indications for hysterectomy. Results Among 1649 women who underwent a hysterectomy (1009 for benign indications and 640 for malignancy), 6% were subsequently readmitted within 30 days (8.9% for malignancy vs 4.2% for benign; P < .0001). The mean time to readmission was 13 days (15 days for malignancy vs 10 days for benign; P = .004). The most common reasons for readmission were gastrointestinal (38%) and infectious (34%) etiologies, and 11.6% of readmitted patients experienced a perioperative complication. Among women undergoing hysterectomy for benign indications, a history of a laparotomy, including cesarean delivery (adjusted odds ratio AOR, 2.12; 95% confidence interval CI, 1.06–4.25; P = .03), as well as a perioperative complication (AOR, 2.41; 95% CI, 1.00–6.04; P = .05) were both associated with a >2-fold increased odds of readmission. Among women undergoing hysterectomy for malignancy, an American Society of Anesthesiologists Physical Status Classification of III or IV (AOR, 1.92; 95% CI, 1.05–3.50; P = .03), a longer length of initial hospitalization (3 days AOR, 7.83; 95% CI, 1.33–45.99; P = .02), and an estimated blood loss >500 mL (AOR, 3.29; 95% CI, 1.28–8.45; P = .01) were associated with a higher odds of readmission; however, women who underwent a laparoscopic hysterectomy (AOR, 0.32; 95% CI, 0.12–0.86; P = .02) and who were discharged on postoperative day 1 (AOR, 0.16; 95% CI, 0.03–0.82; P = .02) were at a decreased risk of readmission. Physician and operative characteristics were not significant predictors of readmission. Conclusion This study found that malignancy, perioperative complications, and prior open abdominal surgery, including cesarean delivery, are significant risk factors for consequent 30-day readmission following index hysterectomy. It may be possible to identify patients at highest risk for readmission at the time of hysterectomy, which can assist in developing interventions to reduce such events.
Abstract
Introduction
There are substantial individual differences (resilience and vulnerability) in neurobehavioral performance from psychosocial stress and sleep loss. However, the time course of ...heart rate variability (HRV) across baseline, total sleep deprivation (TSD), the combination of TSD + psychological stress, and recovery has not been investigated; in addition, it remains unknown whether HRV and blood pressure (BP) differ in resilient vs. vulnerable individuals and predict individual differences in cognitive performance.
Methods
Thirty-one healthy adults (ages 27–53; mean±SD, 35.4±7.1y; 14 females) participated in a five-day experiment consisting of two 8h time-in-bed (TIB) baseline nights, 39h TSD, and two 8h-10h TIB recovery nights. A modified Trier Social Stress Test (TSST) induced psychological stress on the TSD day. Systolic and diastolic BP and HRV (derived from echocardiographic R-R interval) were obtained at six time points (pre-study, baseline, during TSD, during TSD after the TSST, after recovery, and post-study). Cognitively resilient (n=15) and vulnerable (n=16) groups were defined by a median split on 10-minute Psychomotor Vigilance Test (PVT) TSD performance total lapses (>500ms response time) and errors. Repeated measures ANOVA and post-hoc comparisons corrected for multiple testing, examined BP and HRV across time points between groups.
Results
HRV showed a significant time*group interaction: while resilient individuals had significantly lower HRV at pre-study compared to vulnerable individuals, their HRV increased above that of vulnerable individuals with TSD and with TSD + psychological stress. By contrast, systolic and diastolic BP did not show significant time*group interactions and did not predict cognitive vulnerability during TSD.
Conclusion
HRV differed between resilient and vulnerable individuals across TSD, psychological stress and recovery sleep and predicted individual differences in cognitive performance, whereby lower HRV during full-rested conditions predicted resilience to TSD and TSD + psychological stress. HRV, but not BP, is a reliable biomarker of sleep deprivation, psychological stress, and neurobehavioral vulnerability.
Support
NASA NNX14AN49G.
Abstract
Introduction
Individuals show robust resilience and vulnerability in neurobehavioral performance to sleep loss and stress. For the first time, we investigated the time course of two ...cardiovascular measurements, stroke volume (SV) and cardiac index (CI), both derived from echocardiography, across baseline, total sleep deprivation (TSD), the combination of TSD+psychological stress, and recovery. We also determined whether these variables differ in resilient vs. vulnerable individuals and whether they predict differential vulnerability in cognitive performance.
Methods
Thirty-one healthy adults (ages 27–53; mean±SD, 35.4±7.1y; 14 females) participated in a five-day experiment consisting of two 8h time-in-bed (TIB) baseline nights, 39h TSD, and two 8h-10h TIB recovery nights. A modified Trier Social Stress Test (TSST) was conducted on the TSD day to induce psychological stress. Echocardiographic measures of SV and CI were obtained at six time points (pre-study, baseline, during TSD, during TSD after the TSST, after recovery, and post-study). A median split of TSD performance total lapses (>500 ms response time) and errors on the 10-minute Psychomotor Vigilance Test (PVT), defined cognitively resilient (n=15) and vulnerable (n=16) groups. Repeated measures ANOVA and post-hoc comparisons corrected for multiple testing, examined SV and CI across time points between groups.
Results
There was a significant time*group interaction for SV: cognitively resilient individuals had greater SV during the five-day experiment. In addition, in both resilient and vulnerable individuals, SV increased with TSD and with TSD+psychological stress compared with baseline. Like SV, there was a significant time*group interaction for CI: resilient individuals had greater CI at all points of the experiment.
Conclusion
SV and CI differed between resilient and vulnerable individuals across TSD, psychological stress and recovery sleep. Greater SV and greater CI at baseline predicted resilience to TSD and TSD+psychological stress. CI and SV are novel physiological biomarkers of sleep loss, stress, and individual differences in cognitive performance.
Support
NASA NNX14AN49G.
Individuals often continue to rely on misinformation in their reasoning and decision making even after it has been corrected. This is known as the continued influence effect, and one of its presumed ...drivers is misinformation familiarity. As continued influence can promote misguided or unsafe behaviours, it is important to find ways to minimize the effect by designing more effective corrections. It has been argued that correction effectiveness is reduced if the correction repeats the to-be-debunked misinformation, thereby boosting its familiarity. Some have even suggested that this familiarity boost may cause a correction to inadvertently increase subsequent misinformation reliance; a phenomenon termed the familiarity backfire effect. A study by Pluviano et al. (2017) found evidence for this phenomenon using vaccine-related stimuli. The authors found that repeating vaccine "myths" and contrasting them with corresponding facts backfired relative to a control condition, ironically increasing false vaccine beliefs. The present study sought to replicate and extend this study. We included four conditions from the original Pluviano et al. study: the myths vs. facts, a visual infographic, a fear appeal, and a control condition. The present study also added a "myths-only" condition, which simply repeated false claims and labelled them as false; theoretically, this condition should be most likely to produce familiarity backfire. Participants received vaccine-myth corrections and were tested immediately post-correction, and again after a seven-day delay. We found that the myths vs. facts condition reduced vaccine misconceptions. None of the conditions increased vaccine misconceptions relative to control at either timepoint, or relative to a pre-intervention baseline; thus, no backfire effects were observed. This failure to replicate adds to the mounting evidence against familiarity backfire effects and has implications for vaccination communications and the design of debunking interventions.
Bioassay-guided fractionation of an organic extract of the cell mass from a manipulated plant cell culture of Mirabilis jalapa led to the isolation and subsequent identification of three new phenolic ...compounds, 1, 2, and 3. The isoflavone 1 and dehydrorotenoid 2 were identified as the principal antifungal principles from this plant cell culture with IC(50)'s of 25 and 48 microg/mL, respectively, against the test organism, Candida albicans DSY1024. The rotenoid 3 was inactive at 200 microg/mL in this assay.
The widespread prevalence and persistence of misinformation in contemporary societies, such as the false belief that there is a link between childhood vaccinations and autism, is a matter of public ...concern. For example, the myths surrounding vaccinations, which prompted some parents to withhold immunization from their children, have led to a marked increase in vaccine-preventable disease, as well as unnecessary public expenditure on research and public-information campaigns aimed at rectifying the situation. We first examine the mechanisms by which such misinformation is disseminated in society, both inadvertently and purposely. Misinformation can originate from rumors but also from works of fiction, governments and politicians, and vested interests. Moreover, changes in the media landscape, including the arrival of the Internet, have fundamentally influenced the ways in which information is communicated and misinformation is spread. We next move to misinformation at the level of the individual, and review the cognitive factors that often render misinformation resistant to correction. We consider how people assess the truth of statements and what makes people believe certain things but not others. We look at people's memory for misinformation and answer the questions of why retractions of misinformation are so ineffective in memory updating and why efforts to retract misinformation can even backfire and, ironically, increase misbelief. Though ideology and personal worldviews can be major obstacles for debiasing, there nonetheless are a number of effective techniques for reducing the impact of misinformation, and we pay special attention to these factors that aid in debiasing. We conclude by providing specific recommendations for the debunking of misinformation. These recommendations pertain to the ways in which corrections should be designed, structured, and applied in order to maximize their impact. Grounded in cognitive psychological theory, these recommendations may help practitioners—including journalists, health professionals, educators, and science communicators—design effective misinformation retractions, educational tools, and public-information campaigns.
PDF
