Biomarkers of Airway Disease, Barrett's and Underdiagnosed Reflux Noninvasively (BAD-BURN) in World Trade Center exposed firefighters: a case-control observational study protocol.

Background: Particulate matter exposure (PM) is a cause of aerodigestive disease globally. The destruction of the World Trade Center (WTC) exposed first responders and inhabitants of New York City to WTC-PM and caused obstructive airways disease (OAD), gastroesophageal reflux disease (GERD) and Barrett's Esophagus (BE). GERD not only diminishes health-related quality of life but also gives rise to complications that extend beyond the scope of BE.

Biomarkers of Airway Disease, Barrett's and Underdiagnosed Reflux Noninvasively (BAD-BURN): a Case-Control Observational Study Protocol.

Background: Particulate matter exposure (PM) is a cause of aerodigestive disease globally. The destruction of the World Trade Center (WTC) exposed fifirst responders and inhabitants of New York City to WTC-PM and caused obstructive airways disease (OAD), gastroesophageal Refux disease (GERD) and Barrett's Esophagus (BE). GERD not only diminishes health-related quality of life but also gives rise to complications that extend beyond the scope of BE.

Polyadenylation of canonical histone H3.1 in carcinogenesis.

Canonical histone messenger RNAs (mRNAs) are transcribed during S phase and do not terminate with a poly(A) tail at the 3' end. Instead, the histone mRNAs display a stem-loop structure at their 3-end. Stem-loop-binding protein (SLBP) binds the stem-loop and regulates canonical histone mRNA metabolism.

Tandem Mass Tagging Based Identification of Proteome Signatures for Reductive Stress Cardiomyopathy.

Nuclear factor erythroid 2-related factor 2 (NRF2), a redox sensor, is vital for cellular redox homeostasis. We reported that transgenic mice expressing constitutively active Nrf2 (CaNrf2-TG) exhibit reductive stress (RS). In this study, we identified novel protein signature for RS-induced cardiomyopathy using Tandem Mass Tag (TMT) proteomic analysis in heart tissues of TG (CaNrf2-TG) mice at 6-7 months of age.

High burden of clonal hematopoiesis in first responders exposed to the World Trade Center disaster.

The terrorist attacks on the World Trade Center (WTC) created an unprecedented environmental exposure to aerosolized dust, gases and potential carcinogens. Clonal hematopoiesis (CH) is defined as the acquisition of somatic mutations in blood cells and is associated with smoking and exposure to genotoxic stimuli. Here we show that deep targeted sequencing of blood samples identified a significantly higher proportion of WTC-exposed first responders with CH (10%; 48 out of 481) when compared with non-WTC-exposed firefighters (6.

Human Rhinovirus Infection of the Respiratory Tract Affects Sphingolipid Synthesis.

The 17q21 asthma susceptibility locus includes asthma risk alleles associated with decreased sphingolipid synthesis, likely resulting from increased expression of ORMDL3. ORMDL3 inhibits serine-palmitoyl transferase (SPT), the rate-limiting enzyme of sphingolipid synthesis. There is evidence that decreased sphingolipid synthesis is critical to asthma pathogenesis.

Food Intake REstriction for Health OUtcome Support and Education (FIREHOUSE) Protocol: A Randomized Clinical Trial.

Fire Department of New York (FDNY) rescue and recovery workers exposed to World Trade Center (WTC) particulates suffered loss of forced expiratory volume in 1 s (FEV). Metabolic Syndrome increased the risk of developing WTC-lung injury (WTC-LI) We aim to attenuate the deleterious effects of WTC exposure through a dietary intervention targeting these clinically relevant disease modifiers. We hypothesize that a calorie-restricted Mediterranean dietary intervention will improve metabolic risk, subclinical indicators of cardiopulmonary disease, quality of life, and lung function in firefighters with WTC-LI.

Increasing Sphingolipid Synthesis Alleviates Airway Hyperreactivity.

Impaired sphingolipid synthesis is linked genetically to childhood asthma and functionally to airway hyperreactivity (AHR). The objective was to investigate whether sphingolipid synthesis could be a target for asthma therapeutics. The effects of GlyH-101 and fenretinide via modulation of sphingolipid synthesis on AHR was evaluated in mice deficient in SPT (serine palmitoyl-CoA transferase), the rate-limiting enzyme of sphingolipid synthesis.

Multiomics of World Trade Center Particulate Matter-induced Persistent Airway Hyperreactivity. Role of Receptor for Advanced Glycation End Products.

Pulmonary disease after World Trade Center particulate matter (WTC-PM) exposure is associated with dyslipidemia and the receptor for advanced glycation end products (RAGE); however, the mechanisms are not well understood. We used a murine model and a multiomics assessment to understand the role of RAGE in the pulmonary long-term effects of a single high-intensity exposure to WTC-PM. After 1 month, WTC-PM-exposed wild-type (WT) mice had airway hyperreactivity, whereas RAGE-deficient () mice were protected.

World Trade Center-Cardiorespiratory and Vascular Dysfunction: Assessing the Phenotype and Metabolome of a Murine Particulate Matter Exposure Model.

Vascular changes occur early in the development of obstructive airways disease. However, the vascular remodeling and dysfunction due to World Trade Center-Particulate Matter (WTC-PM) exposure are not well described and are therefore the focus of this investigation. C57Bl/6 female mice oropharyngeally aspirated 200 µg of WTC-PM or phosphate-buffered saline (PBS) (controls).

Receptor for advanced glycation end-products and environmental exposure related obstructive airways disease: a systematic review.

Background: Our group has identified the receptor for advanced glycation end-products (RAGE) as a predictor of World Trade Center particulate matter associated lung injury. The aim of this systematic review is to assess the relationship between RAGE and obstructive airways disease secondary to environmental exposure.

Methods: A comprehensive search using PubMed and Embase was performed on January 5, 2018 utilising keywords focusing on environmental exposure, obstructive airways disease and RAGE and was registered with PROSPERO (CRD42018093834).

Validation of Predictive Metabolic Syndrome Biomarkers of World Trade Center Lung Injury: A 16-Year Longitudinal Study.

Background: Metabolic syndrome (MetSyn) predicted future development of World Trade Center lung injury (WTC-LI) in a subgroup of firefighters who never smoked and were male. An intracohort validation of MetSyn as a predictor of WTC-LI is examined in the cohort exposed to the World Trade Center (WTC) that has been followed longitudinally for 16 years.

Methods: Results of pulmonary function tests (n = 98,221) in workers exposed to the WTC (n = 9,566) were evaluated.

Non-Cardiac Chest Pain: A Review of Environmental Exposure-Associated Comorbidities and Biomarkers.

The prevalence of non-cardiac chest pain (NCCP) ranges from 13-33%. A majority of those presenting with a chief complaint of chest pain are found to have a diagnosis of NCCP. Aerodigestive diseases are a cause of NCCP, and billions of dollars are spent annually on the treatment of NCCP.

Metabolic Syndrome and Air Pollution: A Narrative Review of Their Cardiopulmonary Effects.

Particulate matter (PM) exposure and metabolic syndrome (MetSyn) are both significant global health burdens. PM exposure has been implicated in the pathogenesis of MetSyn and cardiopulmonary diseases. Individuals with pre-existing MetSyn may be more susceptible to the detrimental effects of PM exposure.

Impaired sphingolipid synthesis in the respiratory tract induces airway hyperreactivity.

Asthma is a clinically heterogeneous genetic disease, and its pathogenesis is incompletely understood. Genome-wide association studies link ORM (yeast)-Like protein isoform 3 [corrected] (ORMDL3), a member of the ORM gene family, to nonallergic childhood-onset asthma. Orm proteins negatively regulate sphingolipid (SL) synthesis by acting as homeostatic regulators of serine palmitoyl-CoA transferase (SPT), the rate-limiting enzyme of de novo SL synthesis, but it is not known how SPT activity or SL synthesis is related to asthma.

Mast cells: a pivotal role in pulmonary fibrosis.

Pulmonary fibrosis is characterized by an inflammatory response that includes macrophages, neutrophils, lymphocytes, and mast cells. The purpose of this study was to evaluate whether mast cells play a role in initiating pulmonary fibrosis. Pulmonary fibrosis was induced with bleomycin in mast-cell-deficient WBB6F1-W/W(v) (MCD) mice and their congenic controls (WBB6F1-(+)/(+)).

Mast cells are required for the development of renal fibrosis in the rodent unilateral ureteral obstruction model.

Mast cells are associated with inflammation and fibrosis. Whether they protect against or contribute to renal fibrosis is unclear. Based on our previous findings that mast cells can express and secrete active renin, and that angiotensin (ANG II) is profibrotic, we hypothesized that mast cells play a critical role in tubulointerstitial fibrosis.

Predicting survival of periviable fetuses using NICHD fetal heart rate categories.

Objective: To evaluate whether National Institute of Child Health and Human Health and Development (NICHD) fetal heart rate categories were predictive of neonatal survival in periviable pregnancies.

Methods: We reviewed the charts of 57 infants delivered at 23 and 24 weeks' gestation. Fetal heart rate tracings were evaluated following the NICHD 2008 criteria, using the acceleration height of 10 bpm and duration of 10 s.

Mast cell renin and a local renin-angiotensin system in the airway: role in bronchoconstriction.

We previously reported that mast cells express renin, the rate-limiting enzyme in the renin-angiotensin cascade. We have now assessed whether mast cell renin release triggers angiotensin formation in the airway. In isolated rat bronchial rings, mast cell degranulation released enzyme with angiotensin I-forming activity blocked by the selective renin inhibitor BILA2157.

Immediate hypersensitivity elicits renin release from cardiac mast cells.

Background: We recently reported that murine and cavian heart mast cells are a unique extrarenal source of renin. Ischemia/reperfusion releases this renin leading to local angiotensin formation and norepinephrine release. As mast cells are a primary target of hypersensitivity, we assessed whether anaphylactic mast cell degranulation also results in renin and norepinephrine release.

Studies on the anti-inflammatory, antipyretic and analgesic properties of the leaves of Aegle marmelos Corr.

The serial extracts of the leaves of Aegle marmelos Corr. were investigated for anti-inflammatory property. The analgesic and antipyretic properties were also evaluated.