Faculty Bibliography

BACKGROUND:Risk of early-stage lung adenocarcinoma (LUAD) recurrence after surgical resection is significant, and post-recurrence median survival is approximately two years. Currently there are no commercially available biomarkers that predict recurrence. Here, we investigated whether microbial and host genomic signatures in the lung can predict recurrence. METHODS:In 91 early-stage (Stage IA/IB) LUAD-patients with extensive follow-up, we used 16s rRNA gene sequencing and host RNA-sequencing to map the microbial and host transcriptomic landscape in tumor and adjacent unaffected lung samples. RESULTS:23 out of 91 subjects had tumor recurrence over 5-year period. In tumor samples, LUAD recurrence was associated with enrichment with Dialister, Prevotella, while in unaffected lung, recurrence was associated with enrichment with Sphyngomonas and Alloiococcus. The strengths of the associations between microbial and host genomic signatures with LUAD recurrence were greater in adjacent unaffected lung samples than in the primary tumor. Among microbial-host features in the unaffected lung samples associated with recurrence, enrichment with Stenotrophomonas geniculata and Chryseobacterium were positively correlated with upregulation of IL-2, IL-3, IL-17, EGFR, HIF-1 signaling pathways among the host transcriptome. In tumor samples, enrichment with Veillonellaceae Dialister, Ruminococcacea, Haemophilus Influenza, and Neisseria were positively correlated with upregulation of IL-1, IL-6, IL17, IFN, and Tryptophan metabolism pathways. CONCLUSIONS:Overall, modeling suggested that a combined microbial/transcriptome approach using unaffected lung samples had the best biomarker performance (AUC=0.83). IMPACT/CONCLUSIONS:This study suggests that LUAD recurrence is associated with distinct pathophysiological mechanisms of microbial-host interactions in the unaffected lung rather than those present in the resected tumor.

BACKGROUND:concentrations have been demonstrated to be exceptionally high when underground, however. Studies on the impact of subway PM exposure on cardiopulmonary health in the United States are limited. METHODS:concentrations and visit type (i.e., subway vs. control). RESULTS:, respectively. There was no change in any of the health metrics, but there was a non-significant trend for SDNN to be lower after subway exposure compared to control exposure. Total symptomatic scores did increase post-subway exposure compared to reported values prior to exposure or after the control visit. No significant changes in cytokine concentrations in any specimen type were observed. Mixed-effects models mostly corroborated these paired comparisons. CONCLUSIONS:Acute exposures to PM on a subway platform do not cause measurable cardiopulmonary effects apart from reductions in HRV and increases in symptoms in healthy volunteers. These findings match other studies that found little to no changes in lung function and blood pressure after exposure in underground subway stations. Future work should still target potentially more vulnerable populations, such as individuals with asthma or those who spend increased time underground on the subway such as transit workers.

Founded in 1947 as the Institute of Industrial Medicine, the Nelson Institute and Department of Environmental Medicine at New York University (NYU) Grossman School of Medicine (NYUGSOM) was supported by a National Institute of Environmental Health Science (NIEHS) Center Grant for over 56 years. Nelson Institute researchers generated 75 years of impactful research in environmental and occupational health, radiation effects, toxicology, and cancer. Environmental health research is continuing at NYUGSOM in its departments of medicine and population health. The objective of this historical commentary is to highlight the major achievements of the Nelson Institute and the department in the context of its history at facilities in Sterling Forest, Tuxedo, NY and Manhattan, NY. Aspects of our discussion include leadership, physical facilities, and research in many areas, including air pollution, health effects of environmental radiation exposures, inhalation toxicology methodology, carcinogenesis by chemicals, metals, and hormones, cancer chemoprevention, human microbiome, ecotoxicology, epidemiology, biostatistics, and community health concerns. The research of the institute and department benefited from unique facilities, strong leadership focused on team-based science, and outstanding investigators, students, and staff. A major lasting contribution has been the training of hundreds of graduate students and postdoctoral fellows, many of whom have been and are training the next generation of environmental and occupational health researchers at various institutions.

Scientific progress and ethical considerations are increasingly shifting the toxicological focus from in vivo animal models to in vitro studies utilizing physiologically relevant cell cultures. Consequently, we evaluated and validated a three-dimensional (3D) model of the human lung using Calu-3 cells cultured at an air-liquid interface (ALI) for 28 days. Assessment of seven essential genes of differentiation and transepithelial electrical resistance (TEER) measurements, in conjunction with mucin (MUC5AC) staining, validated the model. We observed a time-dependent increase in TEER, genetic markers of mucus-producing cells (muc5ac, muc5b), basal cells (trp63), ciliated cells (foxj1), and tight junctions (tjp1). A decrease in basal cell marker krt5 levels was observed. Subsequently, we utilized this validated ALI-cultured Calu-3 model to investigate the adversity of the aerosols generated from three flavored electronic cigarette (EC) e-liquids: cinnamon, vanilla tobacco, and hazelnut. These aerosols were compared against traditional cigarette smoke (3R4F) to assess their relative toxicity. The aerosols generated from PG/VG vehicle control, hazelnut and cinnamon e-liquids, but not vanilla tobacco, significantly decreased TEER and increased lactate dehydrogenase (LDH) release compared to the incubator and air-only controls. Compared to 3R4F, there were no significant differences in TEER or LDH with the tested flavored EC aerosols other than vanilla tobacco. This starkly contrasted our expectations, given the common perception of e-liquids as a safer alternative to cigarettes. Our study suggests that these results depend on flavor type. Therefore, we strongly advocate for further research, increased user awareness regarding flavors in ECs, and rigorous regulatory scrutiny to protect public health.

OBJECTIVE:), is associated with oxidative stress, DNA damage and inflammation, leading to premature signs of skin aging. Because much of the damage results from oxidative stress, we examined the effects of a topical composition containing three antioxidants in an in vitro model system to assess the potential for amelioration of premature aging. The use of multiple antioxidants was of interest based on the typical composition of therapeutic skincare products. It is important to determine the efficacy of multiple antioxidants together and develop a short-term assay for larger scale efficacy testing. METHODS:in the presence and absence of an antioxidant mixture of resveratrol, niacinamide and GHK peptide. Endpoints related to inflammation, premature aging and carcinogenicity were monitored after 5 h of exposure and included IL-6, CXCL10, MMP-1 and NRF2. Differentially expressed genes were monitored by RNA-seq. RESULTS:and suppressed by antioxidants. CONCLUSIONS:Specific signalling pathways known to be correlated with skin inflammation and aging were examined based on their suitability for use in efficacy testing for the prevention of skin damage due to ambient hydrocarbon pollution. Endpoints examined after only 5 h of exposure provide a useful method amenable to high through-put screening. The results obtained reinforce the concept that a multiple antioxidant preparation, topically applied, may reduce pro-inflammatory signalling and cellular damage and thereby reduce premature skin aging due to exposure to rural-derived airborne pollution.

BACKGROUND:Air pollution is a health risk in pregnant women and children. Despite the importance of refined exposure assessment, the characterisation of personalised air pollution exposure remains a challenge in paediatric and perinatal epidemiology. OBJECTIVE:We used portable personal air monitors to characterise personalised exposure to air pollutants in pregnant women. METHODS:), and volatile organic compounds (average use = 14 days). Data were stored in real-time on a secure database via synchronisation with a smartphone application. Of 497 women who agreed to use air monitors, 273 women (55%) were successful in using air monitors for longer than a day. For these participants, we identified daily patterns of exposure to air pollutants using functional principal component analysis (3827 days of air monitoring). RESULTS:had higher daily variations compared to PM. CONCLUSIONS:Small wearables are useful for the measurement of personalised air pollution exposure in birth cohorts and identify daily patterns that cannot be captured otherwise. Successful participation, however, depends on certain individual characteristics. Future studies should consider strategies in design and analysis to account for selective participation.

In this study we investigated the concentration and composition of particulate matter (PM2.5) in the New York City subway system. Realtime measurements, at a 1-s cadence, and gravimetric measurements were performed inside train cars along 300 km of nine subway lines, as well as on 333 platforms on 287 subway stations. The mean (±SD) PM2.5 concentration on the underground platforms was 142 ± 69 μg/m³ versus 29 ± 20 μg/m³ for aboveground stations. The average concentrations inside train cars were 88 ± 14 μg/m³ when traveling through underground tunnels and platforms and 29 ± 31 μg/m³ while on aboveground tracks. The particle composition analysis of filtered samples was done using X-ray fluorescence (XRF), revealing that iron made up approximately 43% of the total PM2.5 mass on station platforms, approximately 126 times higher than the outdoor ambient iron concentration. Other trace elements include silicon, sulfur, copper, nickel, aluminum, calcium, barium, and manganese. Considering the very high iron content, the comparative analysis of the measured concentration versus the standards set by the Environmental Protection Agency (US EPA) is not appropriate since those limits are largely based on particulate matter from fossil fuel combustion. Health impact analysis of inhalation of iron-based particles is needed to contextualize the results presented here.