Background For patients resuscitated from out-of-hospital cardiac arrest (OHCA), the American Heart Association recommends regionalized care at cardiac resuscitation centers that are aligned with ...ST-segment elevation myocardial infarction (STEMI) centers. The effectiveness of treatment at STEMI centers remains unknown. Objective To evaluate whether good neurologic recovery after OHCA is associated with treatment at an STEMI center and if volume of admitted OHCA patients is associated with good neurologic recovery. Methods We included patients in the 2011 California Office of Statewide Health Planning and Development database with a “present on admission” diagnosis of cardiac arrest. Primary outcome was good neurologic recovery at hospital discharge. Hierarchical multiple logistic regression models were used to determine the association between treating hospital and good neurologic recovery after adjusting for patient factors (age, sex, race, ethnicity, insurance type, and ventricular arrest rhythm) and hospital factors (hospital size, intensive care unit bed days, trauma center designation, and teaching status). Results We included 7,725 patients; two-thirds (5,202) were treated at an STEMI center and 1,869 (24%, 95% CI 23%-25%) had good neurologic recovery. After adjustment, treatment at an STEMI center with ≥40 and <40 OHCA cases/year were associated with good neurologic recovery (odds ratio 1.32 95% CI 1.06-1.64 and 1.63 95% CI 1.35-1.97, respectively). Higher volume of admitted OHCA patients was associated with decreased odds of good neurologic recovery (adjusted odds ratio per 10 patients 0.96, 95% CI 0.92-1.00), but this association was not statistically significant after excluding the highest-volume outlier. Conclusions Treatment at an STEMI center—regardless of its annual OHCA volume—after resuscitation from OHCA is associated with good neurologic recovery. Regionalized systems of care should prioritize STEMI centers as destinations for resuscitated OHCA patients.
The authors developed an intervention to improve the quality of the handoff of hospitalized patients; it was associated with reductions in medical errors and in preventable adverse events. Handoff ...duration, time with patients, and time spent on computers did not change.
Preventable adverse events — injuries due to medical errors — are a major cause of death among Americans. Although some progress has been made in reducing certain types of adverse events,
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overall rates of errors remain extremely high.
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Failures of communication, including miscommunication during handoffs of patient care from one resident to another, are a leading cause of errors; such miscommunications contribute to two of every three “sentinel events,” the most serious events reported to the Joint Commission.
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The omission of critical information and the transfer of erroneous information during handoffs are common.
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As resident work hours have been . . .
Little is known about human entrainment under natural conditions, partly due to the complexity of human behavior, torn between biological and social time and influenced by zeitgebers (light-dark ...cycles) that are progressively "polluted" (and thereby weakened) by artificial light. In addition, data about seasonal variations in sleep parameters are scarce. We, therefore, investigated seasonal variation in cross-sectional assessments of sleep/wake times of 9765 subjects from four European populations (EGCUT = Estonian Genome Centre, University of Tartu in Estonia; KORA = Cooperative Health Research in the Region of Augsburg in Germany; KORCULA = The Korcula study in Croatia; and ORCADES = The Orkney Complex Disease Study in Scotland). We identified time-of-year dependencies for the distribution of chronotype (phase of entrainment assessed as the mid-sleep time point on free days adjusted for sleep deficit of workdays) in cohorts from Estonia (EGCUT) and Germany (KORA). Our results indicate that season (defined as daylight saving time - DST and standard zonetime periods - SZT) specifications of photoperiod influence the distribution of chronotype (adjusted for age and sex). Second, in the largest investigated sample, from Estonia (EGCUT; N = 5878), we could detect that seasonal variation in weekly average sleep duration was dependent on individual chronotype. Later chronotypes in this cohort showed significant variation in their average sleep duration across the year, especially during DST (1 h advance in social time from the end of March to end of October), while earlier chronotypes did not. Later chronotypes not only slept less during the DST period but the average chronotype of the population assessed during this period was earlier than during the SZT (local time for a respective time zone) period. More in detail, hierarchical multiple regression analyses showed that, beyond season of assessment (DST or SZT), social jetlag (SJl; the discrepancy between the mid sleep on free and work days - which varied with age and sex) contributed to a greater extent to the variation in sleep duration than chronotype (after taking into account factors that are known to influence sleep duration, i.e. age, sex and body mass index). Variation in chronotype was also dependent on age, sex, season of assessment and SJl (which is highly correlated with chronotype - SJl was larger among later chronotypes). In summary, subjective assessments of sleep/wake times are very reliable to assess internal time and sleep duration (e.g. reproducing sleep duration and timing tendencies related to age and sex across the investigated populations), but season of assessment should be regarded as a potential confounder. We identified in this study photoperiod (seasonal adaptation) and SJl as two main factors influencing seasonal variation in chronotype and sleep duration. In conclusion, season of assessment, sex and age have an effect on epidemiological variation in sleep duration, chronotype and SJl, and should be included in studies investigating associations between these phenotypes and health parameters, and on the development of optimal prevention strategies.
Post-translational modifications diversify protein functions and dynamically coordinate their signalling networks, influencing most aspects of cell physiology. Nevertheless, their genetic regulation ...or influence on complex traits is not fully understood. Here, we compare the genetic regulation of the same PTM of two proteins - glycosylation of transferrin and immunoglobulin G (IgG). By performing genome-wide association analysis of transferrin glycosylation, we identify 10 significantly associated loci, 9 of which were not reported previously. Comparing these with IgG glycosylation-associated genes, we note protein-specific associations with genes encoding glycosylation enzymes (transferrin - MGAT5, ST3GAL4, B3GAT1; IgG - MGAT3, ST6GAL1), as well as shared associations (FUT6, FUT8). Colocalisation analyses of the latter suggest that different causal variants in the FUT genes regulate fucosylation of the two proteins. Glycosylation of these proteins is thus genetically regulated by both shared and protein-specific mechanisms.
To efficiently transform genetic associations into drug targets requires evidence that a particular gene, and its encoded protein, contribute causally to a disease. To achieve this, we employ a ...three-step proteome-by-phenome Mendelian Randomization (MR) approach. In step one, 154 protein quantitative trait loci (pQTLs) were identified and independently replicated. From these pQTLs, 64 replicated locally-acting variants were used as instrumental variables for proteome-by-phenome MR across 846 traits (step two). When its assumptions are met, proteome-by-phenome MR, is equivalent to simultaneously running many randomized controlled trials. Step 2 yielded 38 proteins that significantly predicted variation in traits and diseases in 509 instances. Step 3 revealed that amongst the 271 instances from GeneAtlas (UK Biobank), 77 showed little evidence of pleiotropy (HEIDI), and 92 evidence of colocalization (eCAVIAR). Results were wide ranging: including, for example, new evidence for a causal role of tyrosine-protein phosphatase non-receptor type substrate 1 (SHPS1; SIRPA) in schizophrenia, and a new finding that intestinal fatty acid binding protein (FABP2) abundance contributes to the pathogenesis of cardiovascular disease. We also demonstrated confirmatory evidence for the causal role of four further proteins (FGF5, IL6R, LPL, LTA) in cardiovascular disease risk.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To reverse the global epidemic of physical inactivity that is responsible for more than 5 million deaths per year, many groups recommend creating “activity-friendly environments.” Such environments ...may have other benefits, beyond facilitating physical activity, but these potential co-benefits have not been well described. The purpose of the present paper is to explore a wide range of literature and conduct an initial summary of evidence on co-benefits of activity-friendly environments. An extensive but non-systematic review of scientific and “gray” literature was conducted. Five physical activity settings were defined: parks/open space/trails, urban design, transportation, schools, and workplaces/buildings. Several evidence-based activity-friendly features were identified for each setting. Six potential outcomes/co-benefits were searched: physical health, mental health, social benefits, safety/injury prevention, environmental sustainability, and economics. A total of 418 higher-quality findings were summarized. The overall summary indicated 22 of 30 setting by outcome combinations showed “strong” evidence of co-benefits. Each setting had strong evidence of at least three co-benefits, with only one occurrence of a net negative effect. All settings showed the potential to contribute to environmental sustainability and economic benefits. Specific environmental features with the strongest evidence of multiple co-benefits were park proximity, mixed land use, trees/greenery, accessibility and street connectivity, building design, and workplace physical activity policies/programs. The exploration revealed substantial evidence that designing community environments that make physical activity attractive and convenient is likely to produce additional important benefits. The extent of the evidence justifies systematic reviews and additional research to fill gaps.
The use of omic modalities to dissect the molecular underpinnings of common diseases and traits is becoming increasingly common. But multi-omic traits can be genetically predicted, which enables ...highly cost-effective and powerful analyses for studies that do not have multi-omics
. Here we examine a large cohort (the INTERVAL study
; n = 50,000 participants) with extensive multi-omic data for plasma proteomics (SomaScan, n = 3,175; Olink, n = 4,822), plasma metabolomics (Metabolon HD4, n = 8,153), serum metabolomics (Nightingale, n = 37,359) and whole-blood Illumina RNA sequencing (n = 4,136), and use machine learning to train genetic scores for 17,227 molecular traits, including 10,521 that reach Bonferroni-adjusted significance. We evaluate the performance of genetic scores through external validation across cohorts of individuals of European, Asian and African American ancestries. In addition, we show the utility of these multi-omic genetic scores by quantifying the genetic control of biological pathways and by generating a synthetic multi-omic dataset of the UK Biobank
to identify disease associations using a phenome-wide scan. We highlight a series of biological insights with regard to genetic mechanisms in metabolism and canonical pathway associations with disease; for example, JAK-STAT signalling and coronary atherosclerosis. Finally, we develop a portal ( https://www.omicspred.org/ ) to facilitate public access to all genetic scores and validation results, as well as to serve as a platform for future extensions and enhancements of multi-omic genetic scores.
Epstein Barr virus (EBV) infects ~ 95% of the population worldwide and is known to cause adverse health outcomes such as Hodgkin's, non-Hodgkin's lymphomas, and multiple sclerosis. There is ...substantial interest and investment in developing infection-preventing vaccines for EBV. To effectively deploy such vaccines, it is vital that we understand the risk factors for infection. Why particular individuals do not become infected is currently unknown. The current literature, describes complex, often conflicting webs of intersecting factors-sociodemographic, clinical, genetic, environmental-, rendering causality difficult to decipher. We aimed to use Mendelian randomization (MR) to overcome the issues posed by confounding and reverse causality to determine the causal risk factors for the acquisition of EBV.
We mapped the complex evidence from the literature prior to this study factors associated with EBV serostatus (as a proxy for infection) into a causal diagram to determine putative risk factors for our study. Using data from the UK Biobank of 8422 individuals genomically deemed to be of white British ancestry between the ages of 40 and 69 at recruitment between the years 2006 and 2010, we performed a genome wide association study (GWAS) of EBV serostatus, followed by a Two Sample MR to determine which putative risk factors were causal.
Our GWAS identified two novel loci associated with EBV serostatus. In MR analyses, we confirmed shorter time in education, an increase in number of sexual partners, and a lower age of smoking commencement, to be causal risk factors for EBV serostatus.
Given the current interest and likelihood of a future EBV vaccine, these factors can inform vaccine development and deployment strategies by completing the puzzle of causality. Knowing these risk factors allows identification of those most likely to acquire EBV, giving insight into what age to vaccinate and who to prioritise when a vaccine is introduced.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Fine structural details of glycans attached to the conserved N-glycosylation site significantly not only affect function of individual immunoglobulin G (IgG) molecules but also mediate inflammation ...at the systemic level. By analyzing IgG glycosylation in 5,117 individuals from four European populations, we have revealed very complex patterns of changes in IgG glycosylation with age. Several IgG glycans (including FA2B, FA2G2, and FA2BG2) changed considerably with age and the combination of these three glycans can explain up to 58% of variance in chronological age, significantly more than other markers of biological age like telomere lengths. The remaining variance in these glycans strongly correlated with physiological parameters associated with biological age. Thus, IgG glycosylation appears to be closely linked with both chronological and biological ages. Considering the important role of IgG glycans in inflammation, and because the observed changes with age promote inflammation, changes in IgG glycosylation also seem to represent a factor contributing to aging.
Glycosylation is the key posttranslational mechanism that regulates function of immunoglobulins, with multiple systemic repercussions to the immune system. Our study of IgG glycosylation in 5,117 individuals from four European populations has revealed very extensive and complex changes in IgG glycosylation with age. The combined index composed of only three glycans explained up to 58% of variance in age, considerably more than other biomarkers of age like telomere lengths. The remaining variance in these glycans strongly correlated with physiological parameters associated with biological age; thus, IgG glycosylation appears to be closely linked with both chronological and biological ages. The ability to measure human biological aging using molecular profiling has practical applications for diverse fields such as disease prevention and treatment, or forensics.
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