Glycerophospholipid metabolism changes association with ozone exposure.

Exposure to ozone (O) has been associated with cardiovascular outcomes in humans, yet the underlying mechanisms of the adverse effect remain poorly understood. We aimed to investigate the association between O exposure and glycerophospholipid metabolism in healthy young adults. We quantified plasma concentrations of phosphatidylcholines (PCs) and lysophosphatidylcholines (lysoPCs) using a UPLC-MS/MS system.

Nasal oxidative stress mediating the effects of colder temperature exposure on pediatric asthma symptoms.

Background: Colder temperature exposure is a known trigger for pediatric asthma exacerbation. The induction of oxidative stress is a known pathophysiologic pathway for asthma exacerbation. However, the role of oxidative stress in linking colder temperature exposure and worsened pediatric asthma symptoms is poorly understood.

Associations between personal apparent temperature exposures and asthma symptoms in children with asthma.

Ambient temperature and relative humidity can affect asthma symptoms. Apparent temperature is a measure of temperature perceived by humans that takes into account the effect of humidity. However, the potential link between personal exposures to apparent temperature and asthma symptoms has not been investigated.

Urinary Amino-PAHs in relation to diesel engine emissions and urinary mutagenicity.

Diesel exhaust has long been of health concern due to established toxicity including carcinogenicity in humans. However, the precise components of diesel engine emissions that drive carcinogenesis are still unclear. Limited work has suggested that nitrated polycyclic aromatic hydrocarbons (NPAHs) such as 1-nitropyrene and 2-nitrofluorene may be more abundant in diesel exhaust.

Associations of circadian rest/activity rhythms with cognition in middle-aged and older adults: Demographic and genetic interactions.

Objectives: Wrist actigraphs (accelerometers) can record motor activity over multiple days and nights. The resulting data can be used to quantify 24-h activity profiles, known as circadian rest-activity rhythms (CRARs). Actigraphic CRARs have been tied to cognitive performance and decline in older adults; however, little is known about links between CRARs and performance or change in specific cognitive domains, or how individual differences may influence these associations.

Efficiency of a randomized confirmatory basket trial design constrained to control the family wise error rate by indication.

Basket trials pool histologic indications sharing molecular pathophysiology, improving development efficiency. Currently, basket trials have been confirmatory only for exceptional therapies. Our previous randomized basket design may be generally suitable in the resource-intensive confirmatory phase, maintains high power even with modest effect sizes, and provides nearly -fold increased efficiency for indications, but controls false positives for the pooled result only.

ARZIMM: A Novel Analytic Platform for the Inference of Microbial Interactions and Community Stability from Longitudinal Microbiome Study.

Dynamic changes of microbiome communities may play important roles in human health and diseases. The recent rise in longitudinal microbiome studies calls for statistical methods that can model the temporal dynamic patterns and simultaneously quantify the microbial interactions and community stability. Here, we propose a novel autoregressive zero-inflated mixed-effects model (ARZIMM) to capture the sparse microbial interactions and estimate the community stability.

Oral cavity response to air pollutant exposure and association with pulmonary inflammation and symptoms in asthmatic children.

Exposure to fine particulate matter (PM) and ozone (O) may lead to inflammation and oxidative damage in the oral cavity, which is hypothesized to contribute to the worsening of airway inflammation and asthma symptoms. In this panel study of 43 asthmatic children aged 5-13 years old, each child had 4 clinic visits with a 2-week interval between two consecutive visits. At each visit, saliva samples were collected and subsequently analyzed for interleukin 6 (IL-6) and eosinophil cationic protein (ECP) as biomarkers of inflammation and malondialdehyde (MDA) as a biomarker of oxidative stress in the oral cavity.

The associations of nitrated polycyclic aromatic hydrocarbon exposures with plasma glucose and amino acids.

Nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) have been widely studied for their mutagenic and carcinogenic effects. This study aims to investigate whether exposure to nitro-PAHs is associated with biomarkers of carbohydrate metabolism, an underlying risk factor for metabolic disorder. Early morning urine and blood samples were longitudinally collected two times with a four-week interval from 43 healthy adults.

AGE/RAGE/DIAPH1 axis is associated with immunometabolic markers and risk of insulin resistance in subcutaneous but not omental adipose tissue in human obesity.

Background/objectives: The incidence of obesity continues to increase worldwide and while the underlying pathogenesis remains largely unknown, nutrient excess, manifested by "Westernization" of the diet and reduced physical activity have been proposed as key contributing factors. Western-style diets, in addition to higher caloric load, are characterized by excess of advanced glycation end products (AGEs), which have been linked to the pathophysiology of obesity and related cardiometabolic disorders. AGEs can be "trapped" in adipose tissue, even in the absence of diabetes, in part due to higher expression of the receptor for AGEs (RAGE) and/or decreased detoxification by the endogenous glyoxalase (GLO) system, where they may promote insulin resistance.

Associations between time-weighted personal air pollution exposure and amino acid metabolism in healthy adults.

The molecular mechanisms underlying the associations between air pollution exposure and adverse cardiopulmonary effects remain to be better understood. Altered amino acid metabolism may plays an important role in the development of cardiopulmonary diseases and may be perturbed by air pollution exposure. To test this hypothesized molecular mechanism, we conducted an association analysis from an existing intervention study to examine the relations of air pollution exposures with amino acids in 43 Chinese healthy adults.

Role of endogenous melatonin in pathophysiologic and oxidative stress responses to personal air pollutant exposures in asthmatic children.

Background: Heightening oxidative stress and inflammation is an important pathophysiological mechanism underlying air pollution health effects in people with asthma. Melatonin can suppress oxidative stress and inflammation in pulmonary and circulatory systems. However, the role of melatonin in the oxidative stress and physiological responses to air pollution exposure has not been examined in children with asthma.

Nitrated Polycyclic Aromatic Hydrocarbons and Arachidonic Acid Metabolisms Relevant to Cardiovascular Pathophysiology: Findings from a Panel Study in Healthy Adults.

Concerns on nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) in the environment have mainly arisen from their mutagenic and carcinogenic effects. The objective of this study is to investigate whether nitro-PAH exposures are associated with biomarkers of cardiovascular pathophysiology. In a panel study design, urines and blood samples were collected up to four times with a 2-week interval from 89 healthy adults.

Personal Exposure to PM Oxidative Potential in Association with Pulmonary Pathophysiologic Outcomes in Children with Asthma.

Fine particulate matter (PM) with a higher oxidative potential has been thought to be more detrimental to pulmonary health. We aim to investigate the associations between personal exposure to PM oxidative potential and pulmonary outcomes in asthmatic children. We measured each of the 43 asthmatic children 4 times for airway mechanics, lung function, airway inflammation, and asthma symptom scores.

Lower Airway Dysbiosis Affects Lung Cancer Progression.

In lung cancer, enrichment of the lower airway microbiota with oral commensals commonly occurs, and models support that some of these bacteria can trigger host transcriptomic signatures associated with carcinogenesis. Here, we show that this lower airway dysbiotic signature was more prevalent in the stage IIIB-IV tumor-node-metastasis lung cancer group and is associated with poor prognosis, as shown by decreased survival among subjects with early-stage disease (I-IIIA) and worse tumor progression as measured by RECIST scores among subjects with stage IIIB-IV disease. In addition, this lower airway microbiota signature was associated with upregulation of the IL17, PI3K, MAPK, and ERK pathways in airway transcriptome, and we identified as the most abundant taxon driving this association.

Associations of ozone exposure with urinary metabolites of arachidonic acid.

Background: Ozone (O) exposure has been associated with biomarkers of platelet activation and oxidative stress. The metabolism of arachidonic acid (AA) plays an important role in platelet activation and oxidative stress. However, AA metabolic pathways have not been examined in relation to O and other air pollutants.

Children's microenvironmental exposure to PM and ozone and the impact of indoor air filtration.

Background: In highly polluted urban areas, personal exposure to PM and O occur daily in various microenvironments. Identifying which microenvironments contribute most to exposure can pinpoint effective exposure reduction strategies and mitigate adverse health impacts.

Methods: This work uses real-time sensors to assess the exposures of children with asthma (N = 39) in Shanghai, quantifying microenvironmental exposure to PM and O.

Efficient two-stage sequential arrays of proof of concept studies for pharmaceutical portfolios.

Previous work has shown that individual randomized "proof-of-concept" (PoC) studies may be designed to maximize cost-effectiveness, subject to an overall PoC budget constraint. Maximizing cost-effectiveness has also been considered for arrays of simultaneously executed PoC studies. Defining Type III error as the opportunity cost of not performing a PoC study, we evaluate the common pharmaceutical practice of allocating PoC study funds in two stages.

Endogenous melatonin mediation of systemic inflammatory responses to ozone exposure in healthy adults.

Background/aim: Melatonin is a free radical scavenger and an anti-inflammatory biomolecule. Air pollution exposure has been associated with increased inflammatory responses. We hypothesize that endogenous melatonin plays a role in inflammatory responses to air pollution exposure.

Malondialdehyde in Nasal Fluid: A Biomarker for Monitoring Asthma Control in Relation to Air Pollution Exposure.

Fine particulate matter (PM) and ozone (O) may exert oxidative damage in the nose, which is hypothesized to be associated with worsened asthma symptoms. This study, hence, is to explore whether an oxidative stress biomarker, malondialdehyde (MDA) in the nasal fluid, has the potential to aid personalized asthma control. In a panel study of 43 asthmatic children, 5-13 years old, each child was measured 4 times with a 2-week interval between consecutive clinic visits.

Inflammatory and oxidative stress responses of healthy adults to changes in personal air pollutant exposure.

Exposure to air pollutants has been associated with respiratory and cardiovascular mortality, but the underlying molecular mechanisms remain inadequately understood. We aimed to examine molecular-level inflammatory and oxidative stress responses to personal air pollutant exposure. Fifty-three healthy adults aged 22-52 were measured three times for their blood inflammatory cytokines and urinary malondialdehyde (MDA, an oxidative stress biomarker) within 2 consecutive months.