Experimental Acute Exposure to Thirdhand Smoke and Changes in the Human Nasal Epithelial Transcriptome: A Randomized Clinical Trial.

Importance:No previous studies have shown that acute inhalation of thirdhand smoke (THS) activates stress and survival pathways in the human nasal epithelium. Objective:To evaluate gene expression in the nasal epithelium of nonsmoking women following acute inhalation of clean air and THS. Design, Setting, and Participants:Nasal epithelium samples were obtained from participants in a randomized clinical trial (2011-2015) on the health effects of inhaled THS. In a crossover design, participants were exposed, head only, to THS and to conditioned, filtered air in a laboratory setting. The order of exposures was randomized and exposures were separated by at least 21 days. Ribonucleic acid was obtained from a subset of 4 healthy, nonsmoking women. Exposures:By chance, women in the subset were randomized to receive clean air exposure first and THS exposure second. Exposures lasted 3 hours. Main Outcomes and Measures:Differentially expressed genes were identified using RNA sequencing with a false-discovery rate less than 0.1. Results:Participants were 4 healthy, nonsmoking women aged 27 to 49 years (mean [SD] age, 42 [10.2] years) with no chronic diseases. A total of 389 differentially expressed genes were identified in nasal epithelium exposed to THS, while only 2 genes, which were not studied further, were affected by clean air. Enriched gene ontology terms associated with stress-induced mitochondrial hyperfusion were identified, such as respiratory electron transport chain (q = 2.84 × 10-3) and mitochondrial inner membrane (q = 7.21 × 10-6). Reactome pathway analysis identified terms associated with upregulation of DNA repair mechanisms, such as nucleotide excision repair (q = 1.05 × 10-2). Enrichment analyses using ingenuity pathway analysis identified canonical pathways related to stress-induced mitochondrial hyperfusion (eg, increased oxidative phosphorylation) (P = .001), oxidative stress (eg, glutathione depletion phase II reactions) (P = .04), and cell survival (z score = 5.026). Conclusions and Relevance:This study found that acute inhalation of THS caused cell stress that led to the activation of survival pathways. Some responses were consistent with stress-induced mitochondrial hyperfusion and similar to those demonstrated previously in vitro. These data may be valuable to physicians treating patients exposed to THS and may aid in formulating regulations for the remediation of THS-contaminated environments

Thirdhand Tobacco Smoke: Emerging Evidence and Arguments for a Multidisciplinary Research Agenda

There is broad consensus regarding the health impact of tobacco use and secondhand smoke exposure, yet considerable ambiguity exists about the nature and consequences of thirdhand smoke (THS). We introduce definitions of THS and THS exposure and review recent findings about constituents, indoor sorption-desorption dynamics, and transformations of THS; distribution and persistence of THS in residential settings; implications for pathways of exposure; potential clinical significance and health effects; and behavioral and policy issues that affect and are affected by THS. Physical and chemical transformations of tobacco smoke pollutants take place over time scales ranging from seconds to months and include the creation of secondary pollutants that in some cases are more toxic (e.g., tobacco-specific nitrosamines). THS persists in real-world residential settings in the air, dust, and surfaces and is associated with elevated levels of nicotine on hands and cotinine in urine of nonsmokers residing in homes previously occupied by smokers. Much still needs to be learned about the chemistry, exposure, toxicology, health risks, and policy implications of THS. The existing evidence on THS provides strong support for pursuing a programmatic research agenda to close gaps in our current understanding of the chemistry, exposure, toxicology, and health effects of THS, as well as its behavioral, economic, and sociocultural considerations and consequences. Such a research agenda is necessary to illuminate the role of THS in existing and future tobacco control efforts to decrease smoking initiation and smoking levels, to increase cessation attempts and sustained cessation, and to reduce the cumulative effects of tobacco use on morbidity and mortality

Smoke-free spaces: a decade of progress, a need for more?

Adoption of smoke-free measures has been one of the central elements of tobacco control activity over the past 30 years. The past decade has seen an increasing number of countries and proportion of the global population covered by smoke-free policies to some extent. Despite reductions in global smoking prevalence, population growth means that the number of non-smokers exposed to the harms caused by secondhand smoke remains high. Smoke-free policy measures have been shown to be useful in protecting non-smokers from secondhand smoke, and can additionally increase cessation and reduce smoking initiation. Policies tend to be aimed primarily at enclosed public or workplace settings with very few countries attempting to control exposure in private or semiprivate spaces such as homes and cars, and, as a result, children may be benefiting less from smoke-free measures than adults. Compliance with legislation also varies by country and there is a need for education and empowerment together with guidance and changing social norms to help deliver the full benefits that smoke-free spaces can bring. Restrictions and policies on use of electronic cigarettes (e-cigarettes) in smoke-free settings require more research to determine the benefits and implications of bystanders’ exposure to secondhand e-cigarette aerosol, dual use and smoking cessation

Melanin and Nicotine: A Review of the Literature

The role of melanin in nicotine uptake and metabolism has received little attention. Because nicotine has been shown to accumulate in tissues containing melanin, exploring links between melanin and nicotine may provide additional clues to understanding smoking behavior and disease effects. To examine the scientific literature on the relationship between melanin and nicotine, we conducted a PubMed search. We also searched online archives of internal tobacco industry documents. We retrieved and reviewed 82 published research papers related to melanin and nicotine or melanin and metabolism of other drugs, and 150 relevant internal tobacco industry documents. The published literature suggests that nicotine may accumulate in human tissues containing melanin and this retention may increase melanin synthesis. Existing research on the relationship between melanin and nicotine lacks an adequate consideration of this relationship’s potential impact, if any, on nicotine metabolism, level of nicotine dependence, and ability to quit smoking. Differential accumulation of nicotine in melanin-containing tissues could have implications for individuals with high levels of melanin

Nanoparticle Formation in the Flame Synthesis of Multicomponent Nanostructured Materials for Clean Energy Applications

This dissertation studies the initial stages of particle formation during the combustion synthesis of multicomponent nanomaterials. Combustion is commonly used for the production of nanomaterials at industrial scales and has advantages of high production rates, low waste generation, and scalability. However, there are limitations in being able to apply this synthesis approach to more advanced multicomponent systems. Gas to particle conversion in flames occurs through precursor decomposition, collisional growth, coagulation, condensation, and sintering. There is a fundamental gap in knowledge on the initial stages of particle formation in flames below 2nm due to measurement difficulties and instrumentation limitations. Using a high resolution differential mobility analyzer, the first mobility spectrum measurements of sub 2nm clusters were presented for single component TiO2 and multicomponent SiO2/TiO2 synthesis demonstrating the importance of discrete clusters during particle growth. Further insight into the nature of sub 2nm clusters were gained through the utilization of an atmospheric-pressure time-of-flight mass spectrometer to measure the chemical composition of sub 2nm clusters. During the combustion synthesis of TiO2, it was revealed that for negatively charged species, chemical ionization plays an important role in the formation of TiO2 clusters while large concentrations of high molecular weight organometallic Ti clusters could be measured. Using similar approaches for silica, intermediates of silica clusters could be identified. The main Si growth pathway was revealed to be through silicic acid clusters, where dehydration, hydrogen abstraction, and hydroxyl radical interactions persist through larger clusters of Si. With multicomponent systems of TiO2 and SiO2, evidence of mixed oxide cluster growth could be seen along with independent cluster growth. Mass mobility plots from tandem ion mobility spectrometry-mass spectrometry further revealed that metal oxide cluster masses were much larger than predicted by the widely utilized Kilpatrick relationship used for mass-mobility correlations. The role of ions during combustion synthesis was further studied through measurements of natively charged, charge conditioned, and neutral particle size distributions. Using current voltage measurements in an electric field, the concentration of ions and electric properties of flames were also used to provide insight into ion properties during combustion synthesis for TiO2 and SiO2. Finally, insight from previous studies on the mechanisms of particle formation were applied in developing a system for the synthesis of niobium doped TiO2 nanostructured thin films towards transparent conducting oxide applications. Using a flame aerosol reactor, highly conductive and transparent thin films could be synthesized while enhanced conductivity was achieved through controlled-niobium doping into the anatase crystal lattice of TiO2. Findings from this dissertation have revealed the complexity of gas to particle conversion mechanisms in the initial stages and are the first step towards developing the ability to design flame aerosol reactors for advanced materials synthesis

Bedeutung des Adipokins CTRP3 für das Fettgewebe und die Entwicklung der Atherosklerose

Atherosklerotisch bedingte Folgeerkrankungen gehören zu den häufigsten Todesursachen in den Industrienationen und sind stark mit dem metabolischen Syndrom assoziiert. Infolge von Überernährung kommt es zu einer Hypertrophie und einer Inflammation des Fettgewebes, zu einer Dysbalance der sekretierten Adipokine und damit zur Induktion von systemisch metabolischen Veränderungen. CTRP3 ist ein Adipokin mit überwiegend antiinflammatorischer Wirkung. Erniedrigte CTRP3-Spiegel sind mit metabolischen und kardiovaskulären Erkrankungen sowie einer erhöhten Mortalität assoziiert. Die Bedeutung von CTRP3 in Bezug auf die Entstehung dieser Erkrankungen in vivo ist jedoch bisher experimentell wenig erforscht. Um Aufschluss über die Funktion von CTRP3 zu erhalten, wurden Mäuse mit adipozytenspezifischem CTRP3-KO nach Fütterung mit einer fett- und cholesterinreichen Diät untersucht und mit einer Kontrollgruppe ohne CTRP3-KO verglichen. Die CTRP3-Defizienz führte in den ersten 6 Wochen der Fütterung zu einer beschleunigten Gewichtszunahme bei erhöhtem Körperfettanteil und war mit einer verstärkten Hypertrophie der Adipozyten sowie einer erhöhten Infiltration von Makrophagen in das Fettgewebe assoziiert. Nach 12 Wochen zeigten sich diese Effekte nicht mehr. Im Plasma konnten erhöhte Konzentrationen von VLDL und Gesamtcholesterin nachgewiesen werden. Nach 12 Wochen waren keine dieser Veränderungen mehr nachweisbar. Ein Einfluss der CTRP3-Defizienz auf die Nüchternglukose, die Glukosetoleranz und die Insulinsensitivität ließ sich nicht nachweisen. Sowohl nach 6 als auch nach 12 Wochen konnte eine erhöhte Plaquebelastung in der Aorta detektiert werden, begleitet von einer erhöhten Akkumulation von Lipiden in der Aortenwurzel und einer erhöhten Infiltration von Makrophagen in den Plaques nach 12 Wochen. Ein erhöhtes Vorkommen von nekrotischen Kernen zeigte sich nicht. Neben den Untersuchungen an CTRP3-KO-Mäusen wurde zudem die Genexpression von CTRP3 in verschiedenen Organen von WT-Mäusen analysiert. Von den getesteten Organen wies die Aorta die größte Expression von CTRP3-mRNA auf. In weiterführenden Arbeiten sollte ein Screening auf systemische Inflammationsmarker erfolgen und die Reversibilität der beobachteten Veränderungen durch Applikation von rekombinantem CTRP3 geprüft werden. Das Angleichen im metabolischen Phänotyp nach 12 Wochen Fütterung ist möglicherweise auf eine kompensatorisch reduzierte Nahrungsaufnahme der CTRP3- KO-Mäuse oder aber auf eine sekundär erworbene Verminderung beziehungsweise ein Funktionsverlust von CTRP3 in CTRP3-WT-Mäusen zurückzuführen und erfordert weitere Analysen. Obwohl CTRP3 hauptsächlich als Adipokin gilt, scheint CTRP3 auch in anderen Organen gebildet zu werden. Hinsichtlich der Atherosklerose bedarf insbesondere die Expression von CTRP3 in der Aorta weiterer Aufklärung. Zusammenfassend zeigt diese Arbeit, dass die adipozytenspezifische Defizienz des Adipokins CTRP3 zur Hypertrophie und Inflammation des Fettgewebes, zu erhöhten Konzentrationen von Cholesterin im Plasma sowie zur Entstehung von Atherosklerose beiträgt

MBL Annual Report 2003

Annual report of the Marine Biological Laboratory in Woods Hole. 2003. Includes lists of students, faculty, and researchers.Publication