AHRR Hypomethylation mediates the association between maternal smoking and metabolic profiles in children.

Background: Tobacco smoking during pregnancy is associated with metabolic dysfunction in children, but mechanistic insights remain limited. Hypomethylation of cg05575921 in the aryl hydrocarbon receptor repressor (AHRR) gene is associated with in utero tobacco smoke exposure. In this study, we evaluated whether AHRR hypomethylation mediates the association between maternal smoking and metabolic dysfunction in children.

Genomic map of candidate human imprint control regions: the imprintome.

Imprinted genes - critical for growth, metabolism, and neuronal function - are expressed from one parental allele. Parent-of-origin-dependent CpG methylation regulates this expression at imprint control regions (ICRs). Since ICRs are established before tissue specification, these methylation marks are similar across cell types.

Study protocol to test the efficacy of self-administration of dexmedetomidine sedative therapy on anxiety, delirium, and ventilator days in critically ill mechanically ventilated patients: an open-label randomized clinical trial.

Background: Administration of sedative and opioid medications to patients receiving mechanical ventilatory support in the intensive care unit is a common clinical practice.

Methods: A two-site randomized open-label clinical trial will test the efficacy of self-management of sedative therapy with dexmedetomidine compared to usual care on anxiety, delirium, and duration of ventilatory support after randomization. Secondary objectives are to compare self-management of sedative therapy to usual care on level of alertness, total aggregate sedative and opioid medication exposure, and ventilator-free days up to day 28 after study enrolment.

Epigenetic Dysregulation of Imprinting and Triple-Negative Breast Cancer.

Genomic imprinting is an inherited form of parent-of-origin specific epigenetic gene regulation that is dysregulated by poor prenatal nutrition and environmental toxins. encodes for TASK3, a pH-regulated potassium channel membrane protein that is overexpressed in 40% of breast cancer. However, gene amplification accounts for increased expression in <10% of these breast cancers.

Prioritizing Research Informing Antibiotic Prophylaxis Guidelines for Knee Arthroplasty Patients.

Introduction: Guidelines for routine antibiotic prophylaxis (AP) before dental procedures to prevent periprosthetic joint infection (PJI) have been hampered by the lack of prospective clinical trials.

Objectives: To apply value-of-information (VOI) analysis to quantify the value of conducting further clinical research to reduce decision uncertainty regarding the cost-effectiveness of AP strategies for dental patients undergoing total knee arthroplasty (TKA).

Methods: An updated decision model and probabilistic sensitivity analysis (PSA) evaluated the cost-effectiveness of AP and decision uncertainty for 3 AP strategies: no AP, 2-y AP, and lifetime AP.

Association between PEG3 DNA methylation and high-grade cervical intraepithelial neoplasia.

Background: Epigenetic mechanisms are hypothesized to contribute substantially to the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer, although empirical data are limited.

Methods: Women (n = 419) were enrolled at colposcopic evaluation at Duke Medical Center in Durham, North Carolina. Human papillomavirus (HPV) was genotyped by HPV linear array and CIN grade was ascertained by biopsy pathologic review.

Associations between maternal obesity, gestational cytokine levels and child obesity in the NEST cohort.

Background: Although maternal systemic inflammation is hypothesized to link maternal pre-pregnancy obesity to offspring metabolic dysfunction, patient empirical data are limited.

Objectives: In this study, we hypothesized that pre-pregnancy obesity alters systemic chemo/cytokines concentrations in pregnancy, and this alteration contributes to obesity in children.

Methods: In a multi-ethnic cohort of 361 mother-child pairs, we measured prenatal concentrations of plasma TNF-α, IL-6, IL-8, IL-1β, IL-4, IFN-γ, IL-12 p70 subunit, and IL-17A using a multiplex ELISA and examined associations of pre-pregnancy obesity on maternal chemo/cytokine levels, and associations of these cytokine levels with offspring body mass index z score (BMI-z) at age 2-6 years using linear regression.

Pharmacogenomics in kidney transplant recipients and potential for integration into practice.

What Is Known And Objective: Pharmacogenomic biomarkers are now used in many clinical care settings and represent one of the successes of precision medicine. Genetic variants are associated with pharmacokinetic and pharmacodynamic changes leading to medication adverse effects and changes in clinical response. Actionable pharmacogenomic variants are common in transplant recipients and have implications for medications used in transplant, but yet are not broadly incorporated into practice.

Cadmium exposure and methylation differences between Whites and African Americans in the NEST Cohort.

Cadmium (Cd) is a ubiquitous environmental pollutant associated with a wide range of health outcomes including cancer. However, obscure exposure sources often hinder prevention efforts. Further, although epigenetic mechanisms are suspected to link these associations, gene sequence regions targeted by Cd are unclear.

Is Antibiotic Prophylaxis Cost-effective for Dental Patients Following Total Knee Arthroplasty?

Introduction: Routine antibiotic prophylaxis (AP) to prevent prosthetic joint infection remains controversial. The lack of prophylaxis guideline consensus from the American Academy of Orthopaedic Surgeons (AAOS) and the American Dental Association (ADA) contributes to clinician confusion.

Objectives: This cost-effectiveness decision model informs the AP debate and guideline development by comparing the benefits, harms, and costs of alternative prophylaxis strategies.

Maternal pre-pregnancy obesity, offspring cord blood DNA methylation, and offspring cardiometabolic health in early childhood: an epigenome-wide association study.

Pre-pregnancy obesity is an established risk factor for adverse sex-specific cardiometabolic health in offspring. Epigenetic alterations, such as in DNA methylation (DNAm), are a hypothesized link; however, sex-specific epigenomic targets remain unclear. Leveraging data from the Newborn Epigenetics Study (NEST) cohort, linear regression models were used to identify CpG sites in cord blood leukocytes associated with pre-pregnancy obesity in 187 mother-female and 173 mother-male offsprings.

Pharmacogenomics of Medications Commonly Used in the Intensive Care Unit.

In the intensive care unit (ICU) setting, where highly variable and insufficient drug efficacies, as well as frequent and unpredictable adverse drug reactions (ADRs) occur, pharmacogenomics (PGx) offers an opportunity to improve health outcomes. However, PGx has not been fully evaluated in the ICU, partly due to lack of knowledge of how genetic markers may affect drug therapy. To fill in this gap, we conducted a review to summarize the PGx information for the medications commonly encountered in the ICU.

A Novel Research Method for Determining Sedative Exposure in Critically Ill Patients.

Background: Although potent sedative and opioid drugs are some of the most commonly used medications to manage pain, anxiety, and discomfort in critically ill patients, conducting clinical trials where sedative and opioid medications are outcome variables within a longitudinal research design can be a methodological challenge.

Objectives: The purpose of this article is to provide in detail a conceptual discussion of the concept and analysis of sedative exposure: A novel research analysis method for aggregating sedative and opioid medication doses from disparate drug classes commonly administered to critically ill patients and used by our team in several clinical research studies.

Methods: Comparing the dose of each sedative and opioid administered to an individual patient (within a defined time interval) to all other patients in a research study receiving the same medications allows for ranking of dosages for each medication by quartiles.

Economic Evaluation of a Patient-Directed Music Intervention for ICU Patients Receiving Mechanical Ventilatory Support.

Objectives: Music intervention has been shown to reduce anxiety and sedative exposure among mechanically ventilated patients. Whether music intervention reduces ICU costs is not known. The aim of this study was to examine ICU costs for patients receiving a patient-directed music intervention compared with patients who received usual ICU care.

Effects of Cadmium Exposure on DNA Methylation at Imprinting Control Regions and Genome-Wide in Mothers and Newborn Children.

Background: Imprinted genes are defined by their preferential expression from one of the two parental alleles. This unique mode of gene expression is dependent on allele-specific DNA methylation profiles established at regulatory sequences called imprinting control regions (ICRs). These loci have been used as biosensors to study how environmental exposures affect methylation and transcription.

DNA methylation of imprinted gene control regions in the regression of low-grade cervical lesions.

The role of host epigenetic mechanisms in the natural history of low-grade cervical intraepithelial neoplasia (CIN1) is not well characterized. We explored differential methylation of imprinted gene regulatory regions as predictors of the risk of CIN1 regression. A total of 164 patients with CIN1 were recruited from 10 Duke University clinics for the CIN Cohort Study.

Letting the Patient Decide: A Case Report of Self-Administered Sedation During Mechanical Ventilation.

It is common for critical care nurses to administer sedative medications to patients receiving mechanical ventilation. Although patient-controlled analgesia is frequently used in practice to promote effective self-management of pain by patients, it is not known if patient-controlled sedation can be used to promote effective self-management of distressing symptoms associated with mechanical ventilation. A randomized pilot trial was conducted to evaluate whether patient self-administered sedation with dexmedetomidine is safe and acceptable for self-management of anxiety during ventilator support.

Perceived Motivating Factors and Barriers for the Completion of Postgraduate Training Among American Pharmacy Students Prior to Beginning Advanced Pharmacy Practice Experiences.

To examine perceived motivating factors and barriers (MFB) to postgraduate training (PGT) pursuit among pharmacy students. Third-year pharmacy students at 13 schools of pharmacy provided demographics and their plan and perceived MFBs for pursuing PGT. Responses were characterized using descriptive statistics.

Safety and Acceptability of Patient-Administered Sedatives During Mechanical Ventilation.

Background: Safety and acceptability of sedative self-administration by patients receiving mechanical ventilation is unknown.

Objectives: To determine if self-administration of dexmedetomidine by patients is safe and acceptable for self-management of anxiety during ventilatory support.

Methods: In a pilot trial in 3 intensive care units, 17 intubated patients were randomly assigned to dexmedetomidine and 20 to usual care.

Using the Beers criteria to identify potentially inappropriate medication use by older adult dental patients.

Background: An aging population indicates that increasing numbers of older adults will seek oral health care and have multiple chronic conditions treated with a number of medications. The authors examined the Medicare Current Beneficiary Survey administrative data set to characterize potentially inappropriate medication (PIM) use by older adults visiting the dentist and related adverse experiences that may affect oral health care.

Methods: The authors used the 2015 Beers criteria to identify PIMs for older adults.