Epigenome-Wide Association Study Reveals CpG Sites Associated with Thyroid Function and Regulatory Effects on .

Thyroid hormones play a key role in differentiation and metabolism and are known regulators of gene expression through both genomic and epigenetic processes including DNA methylation. The aim of this study was to examine associations between thyroid hormones and DNA methylation. We carried out a fixed-effect meta-analysis of epigenome-wide association study (EWAS) of blood DNA methylation sites from 8 cohorts from the ThyroidOmics Consortium, incorporating up to 7073 participants of both European and African ancestry, implementing a discovery and replication stage.

Epigenome-wide association meta-analysis of DNA methylation with coffee and tea consumption.

Coffee and tea are extensively consumed beverages worldwide which have received considerable attention regarding health. Intake of these beverages is consistently linked to, among others, reduced risk of diabetes and liver diseases; however, the mechanisms of action remain elusive. Epigenetics is suggested as a mechanism mediating the effects of dietary and lifestyle factors on disease onset.

GWAS of QRS duration identifies new loci specific to Hispanic/Latino populations.

Background: The electrocardiographically quantified QRS duration measures ventricular depolarization and conduction. QRS prolongation has been associated with poor heart failure prognosis and cardiovascular mortality, including sudden death. While previous genome-wide association studies (GWAS) have identified 32 QRS SNPs across 26 loci among European, African, and Asian-descent populations, the genetics of QRS among Hispanics/Latinos has not been previously explored.

Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline.

Cellular senescence, which is characterized by an irreversible cell-cycle arrest accompanied by a distinctive secretory phenotype, can be induced through various intracellular and extracellular factors. Senescent cells that express the cell cycle inhibitory protein p16 have been found to actively drive naturally occurring age-related tissue deterioration and contribute to several diseases associated with ageing, including atherosclerosis and osteoarthritis. Various markers of senescence have been observed in patients with neurodegenerative diseases; however, a role for senescent cells in the aetiology of these pathologies is unknown.

PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity.

Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity.

DNA Methylation Signatures of Depressive Symptoms in Middle-aged and Elderly Persons: Meta-analysis of Multiethnic Epigenome-wide Studies.

Importance: Depressive disorders arise from a combination of genetic and environmental risk factors. Epigenetic disruption provides a plausible mechanism through which gene-environment interactions lead to depression. Large-scale, epigenome-wide studies on depression are missing, hampering the identification of potentially modifiable biomarkers.

Epigenetic Signatures of Cigarette Smoking.

Background: DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders.

Methods And Results: To comprehensively determine the association between cigarette smoking and DNA methylation, we conducted a meta-analysis of genome-wide DNA methylation assessed using the Illumina BeadChip 450K array on 15 907 blood-derived DNA samples from participants in 16 cohorts (including 2433 current, 6518 former, and 6956 never smokers). Comparing current versus never smokers, 2623 cytosine-phosphate-guanine sites (CpGs), annotated to 1405 genes, were statistically significantly differentially methylated at Bonferroni threshold of P<1×10 (18 760 CpGs at false discovery rate <0.

Mercury Ion Clock for a NASA Technology Demonstration Mission.

There are many different atomic frequency standard technologies but only few meet the demanding performance, reliability, size, mass, and power constraints required for space operation. The Jet Propulsion Laboratory is developing a linear ion-trap-based mercury ion clock, referred to as DSAC (Deep-Space Atomic Clock) under NASA's Technology Demonstration Mission program. This clock is expected to provide a new capability with broad application to space-based navigation and science.

In the Absence of a Mechanical Bowel Prep, Does the Addition of Pre-Operative Oral Antibiotics to Parental Antibiotics Decrease the Incidence of Surgical Site Infection after Elective Segmental Colectomy?

Background: Pre-operative oral antibiotics administered the day prior to elective colectomy have been shown to decrease the incidence of surgical site infections (SSI) if a mechanical bowel prep (MBP) is used. Recently, the role for mechanical bowel prep has been challenged as being unnecessary and potentially harmful. We hypothesize that if MBP is omitted, oral antibiotics do not alter the incidence of SSI following colectomy.

Whence Resistance?

Background: Antimicrobial resistance results from a complex interaction between pathogenic and non-pathogenic bacteria, antimicrobial pressure, and genes, which together comprise the total body of potential resistance elements. The purpose of this study is to review and evaluate the importance of antimicrobial pressure on the development of resistance in a single surgical intensive care unit.

Methods: We reviewed a prospectively collected dataset of all intensive care unit (ICU)-acquired infections in surgical and trauma patients over a 6-y period at a single hospital.

Hypocaloric compared with eucaloric nutritional support and its effect on infection rates in a surgical intensive care unit: a randomized controlled trial.

Background: Proper caloric intake goals in critically ill surgical patients are unclear. It is possible that overnutrition can lead to hyperglycemia and an increased risk of infection.

Objective: This study was conducted to determine whether surgical infection outcomes in the intensive care unit (ICU) could be improved with the use of hypocaloric nutritional support.

Characteristics of surgical patients receiving inappropriate empiric antimicrobial therapy.

Background: Inappropriate antibiotics have been observed to result in an increased duration of antibiotic treatment and hospital length of stay, development of multidrug-resistant organisms, and mortality rate compared with appropriate antibiotic treatment. Few studies have evaluated independent risk factors associated with inappropriateness. The purpose of this study was to identify independent predictors of inappropriate, empiric antimicrobial therapy for the treatment of severe sepsis.

Does it Matter if we get it right? Impact of appropriateness of empiric antimicrobial therapy among surgical patients.

Previous studies have shown conflicting evidence regarding the impact of inappropriate, initial antibiotic therapy. The purpose of this study was to evaluate the impact of inappropriate empiric antimicrobial therapy for the treatment of infection among surgical patients. We hypothesized that inappropriate empiric antimicrobial therapy would predict increased mortality risk compared with appropriate therapy.

Sex- and diagnosis-dependent differences in mortality and admission cytokine levels among patients admitted for intensive care.

Objectives: To investigate the role of sex on cytokine expression and mortality in critically ill patients.

Design: A cohort of patients admitted to were enrolled and followed over a 5-year period.

Setting: Two university-affiliated hospital surgical and trauma ICUs.

Continuous intraoperative temperature measurement and surgical site infection risk: analysis of anesthesia information system data in 1008 colorectal procedures.

Objectives: To investigate the association between intraoperative temperature and surgical site infection (SSI) in colorectal surgery with anesthesia information system data.

Methods: Continuously measured intraoperative anesthesia information system temperature data for adult abdominal colorectal surgery procedures at a large tertiary center for 1 year were linked to 30-day American College of Surgeons National Surgical Quality Improvement Program SSI outcomes. Univariable and multivariable analyses of SSI to descriptive temperature statistics, absolute and relative temperature threshold times, and other clinically relevant variables were performed.

Model for End-stage Liver Disease (MELD) in predicting postoperative mortality of patients undergoing colorectal surgery.

The Model for End-stage Liver Disease (MELD) score was previously shown to predict perioperative mortality in patients with cirrhosis undergoing a variety of nontransplant surgical procedures. We sought to determine its usefulness in predicting postoperative mortality in patients undergoing colorectal procedures. National Surgical Quality Improvement Program data were gathered for adult patients undergoing elective and emergent colorectal procedures (Current Procedural Terminology codes 44005 through 45563 excluding appendectomy) during 2005 and 2006 at participating centers.

Mortality factors in geriatric blunt trauma patients: creation of a highly predictive statistical model for mortality using 50,765 consecutive elderly trauma admissions from the National Sample Project.

Elderly patients are at high risk for mortality after injury. We hypothesized that trauma benchmarking efforts would benefit from development of a geriatric-specific model for risk-adjusted analyses of trauma center outcomes. A total of 57,973 records of elderly patients (age older than 65 years), which met our selection criteria, were submitted to the National Trauma Database and included within the National Sample Project between 2003 and 2006.

Aggressive versus conservative initiation of antimicrobial treatment in critically ill surgical patients with suspected intensive-care-unit-acquired infection: a quasi-experimental, before and after observational cohort study.

Background: Antimicrobial treatment in critically ill patients can either be started as soon as infection is suspected or after objective data confirm an infection. We postulated that delaying antimicrobial treatment of patients with suspected infections in the surgical intensive care unit (SICU) until objective evidence of infection had been obtained would not worsen patient mortality.

Methods: We did a 2-year, quasi-experimental, before and after observational cohort study of patients aged 18 years or older who were admitted to the SICU of the University of Virginia (Charlottesville, VA, USA).