Assessing medical product safety during pregnancy using parameterizable tools in the sentinel distributed database.

Purpose: The US Food and Drug Administration established the Sentinel System to monitor the safety of medical products. A component of this system includes parameterizable analytic tools to identify mother-infant pairs and evaluate infant outcomes to enable the routine monitoring of the utilization and safety of drugs used in pregnancy. We assessed the feasibility of using the data and tools in the Sentinel System by assessing a known association between topiramate use during pregnancy and oral clefts in the infant.

A new analytic tool for assessing the impact of the US Food and Drug Administration regulatory actions.

Purpose: Develop and test a flexible, scalable tool using interrupted time series (ITS) analysis to assess the impact of Food and Drug Administration (FDA) regulatory actions on drug use.

Methods: We applied the tool in the Sentinel Distributed Database to assess the impact of FDA's 2010 drug safety communications (DSC) concerning the safety of long-acting beta2-agonists (LABA) in adult asthma patients. We evaluated changes in LABA use by measuring the initiation of LABA alone and concomitant use of LABA and asthma controller medications (ACM) after the DSCs.

Correlates of tobacco product initiation among youth and young adults between waves 1-4 of the population assessment of tobacco and Health (PATH) study (2013-2018).

Introduction: While risk factors for cigarette smoking among youth and young adults are well-documented, less is known about the correlates of initiation of other tobacco products. This study aims to provide estimates and correlates of initiation among U.S.

Prescription medication use and baseline health status of women with live-birth deliveries in a national data network.

Background: The US Food and Drug Administration increasingly uses administrative databases to conduct surveillance of medications used during pregnancy. To assess adverse fetal effects, administrative records must be linked between the mother and infant. The Sentinel Initiative's Mother-Infant Linkage Table provides a large cohort of linked deliveries from national, regional, and public insurance claims in the United States for the US Food and Drug Administration to conduct surveillance.

Changes in Cigarettes per Day and Biomarkers of Exposure Among US Adult Smokers in the Population Assessment of Tobacco and Health Study Waves 1 and 2 (2013-2015).

Introduction: Some studies have found some reduction in tobacco exposure and tobacco-related disease risk with decreased numbers of cigarettes smoked per day (CPD), but biomarker of exposure estimates by change in CPD are generally unavailable for the US population.

Methods: We analyzed biomarker of exposure data by smoking status from over 1100 adult exclusive daily cigarette smokers in Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study who were either exclusive daily smokers or had quit tobacco use entirely at Wave 2. Wave 1 smoking categories consisted of "very light" (1-4 CPD), "light" (5-9 CPD), "moderate" (10-19 CPD), and "heavy" (20+ CPD), and Wave 2 categories were "quitters" (stopped smoking entirely), exclusive cigarette "reducers" (CPD decreased ≥ 50%), "maintainers" (CPD within 50%-150% of Wave 1 value), and "increasers" (CPD increased ≥ 50%).

A neuroglobin-based high-affinity ligand trap reverses carbon monoxide-induced mitochondrial poisoning.

Carbon monoxide (CO) remains the most common cause of human poisoning. The consequences of CO poisoning include cardiac dysfunction, brain injury, and death. CO causes toxicity by binding to hemoglobin and by inhibiting mitochondrial cytochrome oxidase (CcO), thereby decreasing oxygen delivery and inhibiting oxidative phosphorylation.

Associations of Cigarettes Smoked Per Day with Biomarkers of Exposure Among U.S. Adult Cigarette Smokers in the Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013-2014).

Background: The dose-response relationships between number of cigarettes smoked per day (CPD) and health outcomes, such as cancer and heart disease, are well established, but much less is known about the relationships between CPD and biomarkers of exposure.

Methods: We analyzed biomarker data by CPD from more than 2,700 adult daily cigarette smokers in Wave 1 of the Population Assessment of Tobacco and Health Study. Tobacco use categories consisted of exclusive cigarette smokers, dual cigarette and e-cigarette users, and dual cigarette and smokeless tobacco users.

Loss of GCN5L1 in cardiac cells disrupts glucose metabolism and promotes cell death via reduced Akt/mTORC2 signaling.

GCN5L1 regulates protein acetylation and mitochondrial energy metabolism in diverse cell types. In the heart, loss of GCN5L1 sensitizes the myocardium to injury from exposure to nutritional excess and ischemia/reperfusion injury. This phenotype is associated with the reduced acetylation of metabolic enzymes and elevated mitochondrial reactive oxygen species (ROS) generation, although the direct molecular targets of GCN5L1 remain largely unknown.

Platelet bioenergetics correlate with muscle energetics and are altered in older adults.

Background: Physical function decreases with age, and though bioenergetic alterations contribute to this decline, the mechanisms by which mitochondrial function changes with age remains unclear. This is partially because human mitochondrial studies require highly invasive procedures, such as muscle biopsies, to obtain live tissue with functional mitochondria. However, recent studies demonstrate that circulating blood cells are potentially informative in identifying systemic bioenergetic changes.

Cigar smoking prevalence and morbidity among US adults, 2000-2015.

Cigar smoking causes many of the same health conditions as cigarettes, but less information is available on prevalence of use trends and the disease burden of cigar smoking in the US. To examine these issues, we analyzed cigar use and health condition data from the National Health Interview Survey from 2000, 2005, 2010, and 2015, estimating prevalence of use by year and over time. We also estimated the number of, and adjusted disease prevalence ratios for, US adults aged ≥35 years with self-reported history of heart disease, stroke, or cancer attributable to cigar smoking.

Cardiac-specific deletion of GCN5L1 restricts recovery from ischemia-reperfusion injury.

GCN5L1 regulates mitochondrial protein acetylation, cellular bioenergetics, reactive oxygen species (ROS) generation, and organelle positioning in a number of diverse cell types. However, the functional role of GCN5L1 in the heart is currently unknown. As many of the factors regulated by GCN5L1 play a major role in ischemia-reperfusion (I/R) injury, we sought to determine if GCN5L1 is an important nexus in the response to cardiac ischemic stress.

Biomarkers of Exposure among U.S. Adult Cigar Smokers: Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013-2014).

Background: Given the diverse cigar market and limited data on biomarker patterns by cigar type, we compared biomarkers of nicotine and tobacco toxicants among cigar smokers and other groups.

Methods: Using Wave 1 urinary biomarker data from 5,604 adults in the Population Assessment of Tobacco and Health (PATH) Study, we compared geometric mean concentrations among cigar-only smokers (all cigars and separately for traditional, cigarillo, and filtered cigars), cigarette-only smokers, dual cigar/cigarette smokers, and never users of tobacco. We calculated geometric mean ratios comparing groups with never users adjusting for sex, age, race/ethnicity, education and creatinine.

Bioenergetic Differences in the Airway Epithelium of Lean Obese Asthmatics Are Driven by Nitric Oxide and Reflected in Circulating Platelets.

Asthma, characterized by airway obstruction and hyper-responsiveness, is more severe and less responsive to treatment in obese subjects. While alterations in mitochondrial function and redox signaling have been implicated in asthma pathogenesis, it is unclear whether these mechanisms differ in lean obese asthmatics. In addition, we previously demonstrated that circulating platelets from asthmatic individuals have altered bioenergetics; however, it is unknown whether platelet mitochondrial changes reflect those observed in airway epithelial cells.

Smokeless tobacco use and circulatory disease risk: a systematic review and meta-analysis.

Objective: Smokeless tobacco use is a public health issue throughout the world, but reviews and analyses of circulatory disease risks associated with smokeless tobacco use may be outdated or incomplete. This study provides a thorough and comprehensive review and meta-analysis of circulatory disease risks in high-income countries, including recently published study estimates.

Methods: We conducted a systematic review of studies of circulatory disease risks associated with smokeless tobacco use in Europe and North America that were identified from electronic databases and reference lists.

Senescence of bone marrow-derived mesenchymal stem cells from patients with idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease for which age is the most important risk factor. Different mechanisms associated with aging, including stem cell dysfunction, have been described to participate in the pathophysiology of IPF. We observed an extrapulmonary effect associated with IPF: increase in cell senescence of bone marrow-derived mesenchymal stem cells (B-MSCs).

The inflammasome potentiates influenza/Staphylococcus aureus superinfection in mice.

Secondary bacterial respiratory infections are commonly associated with both acute and chronic lung injury. Influenza complicated by bacterial pneumonia is an effective model to study host defense during pulmonary superinfection due to its clinical relevance. Multiprotein inflammasomes are responsible for IL-1β production in response to infection and drive tissue inflammation.

Nocturnal Hypoxia Improves Glucose Disposal, Decreases Mitochondrial Efficiency, and Increases Reactive Oxygen Species in the Muscle and Liver of C57BL/6J Mice Independent of Weight Change.

Although acute exposure to hypoxia can disrupt metabolism, longer-term exposure may normalize glucose homeostasis or even improve glucose disposal in the presence of obesity. We examined the effects of two-week exposure to room air (Air), continuous 10% oxygen (C10%), and 12 hr nocturnal periods of 10% oxygen (N10%) on glucose disposal, insulin responsiveness, and mitochondrial function in lean and obese C57BL/6J mice. Both C10% and N10% improved glucose disposal relative to Air in lean and obese mice without evidence of an increase in insulin responsiveness; however, only the metabolic improvements with N10% exposure occurred in the absence of confounding effects of weight loss.

Electronic nicotine delivery system (ENDS) battery-related burns presenting to US emergency departments, 2016.

Background: Currently, an estimated 7.9 million US adults use electronic nicotine delivery systems (ENDS). Although published reports have identified fires and explosions related to use of ENDS since 2009, these reports do not provide national estimates of burn injuries associated with ENDS batteries in the US.

Differential mitochondrial dinitrosyliron complex formation by nitrite and nitric oxide.

Nitrite represents an endocrine reserve of bioavailable nitric oxide (NO) that mediates a number of physiological responses including conferral of cytoprotection after ischemia/reperfusion (I/R). It has long been known that nitrite can react with non-heme iron to form dinitrosyliron complexes (DNIC). However, it remains unclear how quickly nitrite-dependent DNIC form in vivo, whether formation kinetics differ from that of NO-dependent DNIC, and whether DNIC play a role in the cytoprotective effects of nitrite.

Tobacco Product Use Among Adults - United States, 2015.

Tobacco use remains the leading cause of preventable disease and death in the United States (1). Despite declining cigarette smoking prevalence among U.S.

US Adult Cigar Smoking Patterns, Purchasing Behaviors, and Reasons for Use According to Cigar Type: Findings From the Population Assessment of Tobacco and Health (PATH) Study, 2013-2014.

Introduction: The US cigar market is diverse, yet until recently most research studies and tobacco surveillance systems have not reported behavioral and related outcomes by cigar type.

Methods: The 2013-2014 Population Assessment of Tobacco and Health Study collected data separately for filtered cigars (FCs), cigarillos, and traditional cigars, which were further distinguished as premium or nonpremium. Descriptive statistics for adult established current smokers of each cigar type and cigarettes were calculated for demographic characteristics, tobacco use patterns, purchasing behaviors and reasons for use.

Point of Sale Scanner Data for Rapid Surveillance of the E-cigarette Market.

Objectives: Describe e-cigarette sales trends and market share from U.S. convenience stores and mass market retailers.

IPF lung fibroblasts have a senescent phenotype.

The mechanisms of aging that are involved in the development of idiopathic pulmonary fibrosis (IPF) are still unclear. Although it has been hypothesized that the proliferation and activation of human lung fibroblasts (hLFs) are essential in IPF, no studies have assessed how this process works in an aging lung. Our goal was to elucidate if there were age-related changes on primary hLFs isolated from IPF lungs compared with age-matched controls.