Sex-differences in reporting of statin-associated diabetes mellitus to the US Food and Drug Administration.

Introduction: Diabetes mellitus (DM) is increasingly recognized as a possible consequence of statin therapy. Secondary analysis of randomized clinical trials and limited observational cohort analyses have suggested that women may be more likely than men to experience statin-associated DM. No analyses of real-world drug safety data addressing this question have been published.

Barriers and facilitators of the use of clinical informatics resources to facilitate pharmacogenomic implementation in resource-limited settings.

Objective: Understand perceived barriers to and facilitators of using clinical informatics applications for pharmacogenomic (PGx) implementation in resource-limited settings.

Materials And Methods: We conducted a qualitative research study using a semi-structured interview guide informed by the Consolidated Framework for Implementation Research (CFIR). Interview questions assessed CFIR contextual determinants related to: electronic health record (EHR) infrastructure; clinical informatics personnel and resources; EHR integration of PGx test results; PGx clinical decision support (CDS) tools; institutional resources; and partner receptivity.

Implementation of clopidogrel pharmacogenetic clinical decision support for a preemptive return of results program.

Purpose: To describe our experiences implementing and iterating CYP2C19 genotype-guided clopidogrel pharmacogenetic clinical decision support (CDS) tools over time in the setting of a large health system-wide, preemptive pharmacogenomics program.

Summary: Clopidogrel-treated patients who are genetically predicted cytochrome P450 isozyme 2C19 (CYP2C19) intermediate or poor metabolizers have an increased risk of atherothrombotic events, some of which can be life-threatening. The Clinical Pharmacogenetics Implementation Consortium provides guidance for the use of clopidogrel based on CYP2C19 genotype in patients with cardiovascular and cerebrovascular diseases.

Patient-Level Exposure to Actionable Pharmacogenomic Medications in a Nationally Representative Insurance Claims Database.

Background: The prevalence of exposure to pharmacogenomic medications is well established but little is known about how long patients are exposed to these medications.

Aim: Our objective was to describe the amount of exposure to actionable pharmacogenomic medications using patient-level measures among a large nationally representative population using an insurance claims database.

Methods: Our retrospective cohort study included adults (18+ years) from the IQVIA PharMetrics Plus for Academics claims database with incident fills of 72 Clinical Pharmacogenetics Implementation Consortium level A, A/B, or B medications from January 2012 through September 2018.

Patients' perspectives of a pharmacist-provided clinical pharmacogenomics service.

To assess the perspectives and experiences of patients who participated in a pharmacist-provided clinical pharmacogenomics (PGx) service. We conducted individual semistructured interviews with 16 patients who received a pharmacist-provided PGx service. Qualitative data were analyzed to identify pertinent themes.

Chikungunya Virus Vaccine Candidate Incorporating Synergistic Mutations Is Attenuated and Protects Against Virulent Virus Challenge.

Background: Chikungunya virus (CHIKV) is an arbovirus that periodically emerges to cause large epidemics of arthritic disease. Although the robust immunity elicited by live-attenuated virus (LAV) vaccine candidates makes them attractive, CHIKV vaccine development has been hampered by a high threshold for acceptable adverse events.

Methods: We evaluated the vaccine potential of a recently described LAV, skeletal muscle-restricted virus (SKE), that exhibits diminished replication in skeletal muscle due to insertion of target sequences for skeletal muscle-specific miR-206.

Household and climate factors influence Aedes aegypti presence in the arid city of Huaquillas, Ecuador.

Arboviruses transmitted by Aedes aegypti (e.g., dengue, chikungunya, Zika) are of major public health concern on the arid coastal border of Ecuador and Peru.

WASP 8: The Next Generation in the 50-year Evolution of USEPA's Water Quality Model.

The Water Quality Analysis Simulation Program (WASP) helps users interpret and predict water quality responses to natural phenomena and manmade pollution for various pollution management decisions. WASP is a dynamic compartment-modeling program for aquatic systems, including both the water column and the underlying benthos. WASP allows the user to investigate 1, 2 and 3 dimensional systems and a variety of pollutant types-including both conventional pollutants (e.

PINK1 attenuates mtDNA release in alveolar epithelial cells and TLR9 mediated profibrotic responses.

We have previously shown that endoplasmic reticulum stress (ER stress) represses the PTEN inducible kinase 1 (PINK1) in lung type II alveolar epithelial cells (AECII) reducing mitophagy and increasing the susceptibility to lung fibrosis. Although increased circulating mitochondrial DNA (mtDNA) has been reported in chronic lung diseases, the contribution of mitophagy in the modulation of mitochondrial DAMP release and activation of profibrotic responses is unknown. In this study, we show that ER stress and PINK1 deficiency in AECII led to mitochondrial stress with significant oxidation and damage of mtDNA and subsequent extracellular release.

Acute psychological stress increases serum circulating cell-free mitochondrial DNA.

Intrinsic biological mechanisms transduce psychological stress into physiological adaptation that requires energy, but the role of mitochondria and mitochondrial DNA (mtDNA) in this process has not been defined in humans. Here, we show that similar to physical injury, exposure to psychological stress increases serum circulating cell-free mtDNA (ccf-mtDNA) levels. Healthy midlife adults exposed on two separate occasions to a brief psychological challenge exhibited a 2-3-fold increase in ccf-mtDNA, with no change in ccf-nuclear DNA levels, establishing the magnitude and specificity for ccf-mtDNA reactivity.

Elastic coupling power stroke mechanism of the F-ATPase molecular motor.

The angular velocity profile of the 120° F-ATPase power stroke was resolved as a function of temperature from 16.3 to 44.6 °C using a Δμ = -31.

A framework for uncertainty and risk analysis in Total Maximum Daily Load applications.

In the United States, the computation of Total Maximum Daily Loads (TMDL) must include a Margin of Safety (MOS) to account for different sources of uncertainty. In practice however, TMDL studies rarely include an explicit uncertainty analysis and the estimation of the MOS is often subjective and even arbitrary. Such approaches are difficult to replicate and preclude the comparison of results between studies.

Wetlands for Wastewater Treatment.

An update on the current research and development of the treatment technologies, which utilize natural processes or passive components in wastewater treatment, is provided in this paper. The main focus is on wetland systems and their applications in wastewater treatment (as an advanced treatment unit or decentralized system), nutrient and pollutant removal (metals, industrial and emerging pollutants including pharmaceutical compounds). A summary of studies involving the effects of vegetation, wetland design and modeling, hybrid and innovative systems, storm water treatment and pathogen removal is also included.

Digital PCR methods improve detection sensitivity and measurement precision of low abundance mtDNA deletions.

Mitochondrial DNA (mtDNA) mutations are a common cause of primary mitochondrial disorders, and have also been implicated in a broad collection of conditions, including aging, neurodegeneration, and cancer. Prevalent among these pathogenic variants are mtDNA deletions, which show a strong bias for the loss of sequence in the major arc between, but not including, the heavy and light strand origins of replication. Because individual mtDNA deletions can accumulate focally, occur with multiple mixed breakpoints, and in the presence of normal mtDNA sequences, methods that detect broad-spectrum mutations with enhanced sensitivity and limited costs have both research and clinical applications.

Wetlands for Wastewater Treatment.

This paper provides a review of the treatment technologies, which utilize natural processes or passive components in wastewater treatment. In particular, this paper primarily focuses on wetland systems and their applications in wastewater treatment (as an advanced treatment unit or decentralized system), nutrient and pollutant removal (single and multiple pollutants, and metals), and emerging pollutant removal (pharmaceuticals). A summary of studies involving the plant (vegetation) effects, wetland design and modeling, hybrid and innovative systems, storm water treatment and pathogen removal is also included.

Anatomy of F1-ATPase powered rotation.

F1-ATPase, the catalytic complex of the ATP synthase, is a molecular motor that can consume ATP to drive rotation of the γ-subunit inside the ring of three αβ-subunit heterodimers in 120° power strokes. To elucidate the mechanism of ATPase-powered rotation, we determined the angular velocity as a function of rotational position from single-molecule data collected at 200,000 frames per second with unprecedented signal-to-noise. Power stroke rotation is more complex than previously understood.