Search

Background:The harmful vascular effects of smoking are well established, but the effects of chronic use of electronic cigarettes (e-cigarettes) on endothelial function are less understood. We hypothesized that e-cigarette use causes changes in blood milieu that impair endothelial function.Methods:Endothelial function was measured in chronic e-cigarette users, chronic cigarette smokers, and nonusers. We measured effects of participants’ sera, or e-cigarette aerosol condensate, on NO and H2O2release and cell permeability in cultured endothelial cells (ECs).Results:E-cigarette users and smokers had lower flow-mediated dilation (FMD) than nonusers. Sera from e-cigarette users and smokers reduced VEGF (vascular endothelial growth factor)-induced NO secretion by ECs relative to nonuser sera, without significant reduction in endothelial NO synthase mRNA or protein levels. E-cigarette user sera caused increased endothelial release of H2O2, and more permeability than nonuser sera. E-cigarette users and smokers exhibited changes in circulating biomarkers of inflammation, thrombosis, and cell adhesion relative to nonusers, but with distinct profiles. E-cigarette user sera had higher concentrations of the receptor for advanced glycation end products (RAGE) ligands S100A8 and HMGB1 (high mobility group box 1) than smoker and nonuser sera, and receptor for advanced glycation end product inhibition reduced permeability induced by e-cigarette user sera but did not affect NO production.Conclusions:Chronic vaping and smoking both impair FMD and cause changes in the blood that inhibit endothelial NO release. Vaping, but not smoking, causes changes in the blood that increase microvascular endothelial permeability and may have a vaping-specific effect on intracellular oxidative state. Our results suggest a role for RAGE in e-cigarette-induced changes in endothelial function.

Introduction The aims of this study were to characterize particle size in a thirdhand smoke (THS) aerosol and measure the effects of controlled inhalational exposure to THS on biomarkers of tobacco smoke exposure, inflammation, and oxidative stress in human subjects. Secondhand cigarette smoke changes physically and chemically after release into the environment. Some of the resulting chemicals persist indoors as thirdhand cigarette smoke. THS that is sorbed to surfaces can emit particles back into the air. Aims and Methods Smoke particle size was measured with a scanning mobility particle sizer and condensation particle counter. Using a crossover study design, 18 healthy nonsmokers received a 3-hour inhalational exposure to THS and to filtered, conditioned air. THS was generated with a smoking machine and aged overnight in a chamber. The chamber was flushed with clean air to create the THS aerosol. The tobacco smoke metabolites cotinine, 3-hydroxycotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) were measured in urine. Vascular endothelial growth factor and interleukin-6 in plasma, and 8-isoprostane in urine, were measured using enzyme-linked immunosorbent assay kits. Results Mean smoke particle size increased with aging (171 to 265 nm). We found significant increases in urinary cotinine and 3-hydroxycotinine after 3 hours of exposure to THS and no significant increases in NNAL, interleukin-6, vascular endothelial growth factor or 8-isoprostane. Conclusions Acute inhalational exposure to 22-hour old tobacco smoke aerosol caused increases in the metabolites of nicotine but not the metabolites of the tobacco-specific nitrosamine NNK (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone). This corroborates the utility of cotinine and NNAL for secondhand and THS exposure screening. Implications This study shows that a 3-hour inhalational exposure to the tobacco smoke aerosol that forms in a room that has been smoked in and left unventilated overnight causes increases in urinary metabolites of nicotine, but not of the tobacco-specific nitrosamine NNK. This suggests that cleaning personnel and others who live and work in rooms polluted with aged or thirdhand cigarette smoke regularly may have inhalational exposures and potential health effects related to their exposure to nicotine and other smoke toxicants.

Growing evidence indicates that thirdhand smoke (THS) exposure induces many adverse health effects. However, it is unclear how THS exposure affects behavior and how host genetic background modulates phenotypic changes. Here we used the Collaborative Cross (CC) mouse population-based model to assess behavioral alterations immediately after THS exposure from 4 to 9 weeks of age. We first measured anxiety-like behavior in six strains using light/dark box combined with a custom multivariate mouse tracking system. We developed an anxiety risk scoring system based on anxiety-related traits and then evaluated the THS impact on them. THS exposure significantly decreased anxiety risk in CC019 (P = 0.002) and CC051 (P = 0.009), but increased anxiety risk in CC036 (P

Tobacco-specific nitrosamines (TSNAs) are emitted during smoking and form indoors by nitrosation of nicotine. Two of them, N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are human carcinogens with No Significant Risk Levels (NSRLs) of 500 and 14 ng day-1, respectively. Another TSNA, 4-(methylnitrosamino)-4-(3-pyridyl) butanal (NNA), shows genotoxic and mutagenic activity in vitro. Here, we present additional evidence of genotoxicity of NNA, an assessment of TSNA dermal uptake, and predicted exposure risks through different pathways. Dermal uptake was investigated by evaluating the penetration of NNK and nicotine through mice skin. Comparable mouse urine metabolite profiles suggested that both compounds were absorbed and metabolized via similar mechanisms. We then investigated the effects of skin constituents on the reaction of adsorbed nicotine with nitrous acid (epidermal chemistry). Higher TSNA concentrations were formed on cellulose and cotton substrates that were precoated with human skin oils and sweat compared to clean substrates. These results were combined with reported air, dust, and surface concentrations to assess NNK intake. Five different exposure pathways exceeded the NSRL under realistic scenarios, including inhalation, dust ingestion, direct dermal contact, gas-to-skin deposition, and epidermal nitrosation of nicotine. These results illustrate potential long-term health risks for nonsmokers in homes contaminated with thirdhand tobacco smoke.

Purpose Spiral metacarpal fractures fixed with 2 non-lagged, interfragmentary cortical screws were tested to failure. The effect of screw size (1.2 mm, 1.5 mm, 2.0 mm, and 2.3 mm) on construct strength was tested in 3-point bending. Methods Three-dimensional-printed metacarpal test models were reproduced from computed tomography scans to reduce the confounding variables of bone density and anatomy, often encountered when using cadavers. Results No significant difference was found between the screw sizes, and the peak failure force was similar. Drill bit fracture and deformation during the insertion of the smallest screw (1.2 mm) as well as model failure during the insertion of the largest screw (2.3 mm) were found in some cases. Conclusions Screws of 1.5 mm and 2.0 mm in diameter were of sufficient strength and did not have the issues encountered with smaller or larger screws. Concerns from previous authors regarding intraoperative fracture were consistent with the pre-testing failure of some 2.3-mm models. Clinical Relevance Screws of 1.5 mm or 2 mm appear adequate for the fixation of spiral fracture patterns in metacarpal shafts using bicortical non-lagged technique with a low risk of fixation complications.

Electrical discharge machining (EDM) is a complex manufacturing process where the correlation of the individual process parameters is not fully known. When introducing new materials or complex, individual geometries in EDM, a satisfactory vector of parameters for the process must be found. This challenge is often encountered in the aerospace industry as well as in mold and tool making. One previously successful method to tackle this challenge is the stochastic optimization procedure Evolutionary Strategy (ES). Utilizing an appropriately chosen objective function, the search for a suitable vector of input parameters may be formulated as a mathematical minimization problem over the parameter space. The ES with a covariance matrix adaption (CMA) was utilized to sample from this parameter space in a stochastic manner. Examining the impact of the CMA within an ES is a promising way to gain better insight into the performance of ES. For this purpose, a vector of input parameters was optimized for a drilling EDM process with a comma and a nested comma ES with CMA. It was found that the comma ES led to a reduction in erosion duration tero of 38 % compared to the initially chosen parameters and the nested comma ES led to a reduction in erosion duration tero of 27 % compared to the same initial parameters. The additional information stored in the covariance matrix enables the ES to find a local optimum of the parameter vector faster and more consistently. This fact is verified by use of visualizations of the covariance matrix on a two-dimensional subspace. From these findings it can be concluded, that for the application of the ES to the optimization of EDM processes the CMA should be performed continuously over all generations as opposed to resetting this matrix after a number of generations.

Introduction: Cannabis regulation and use are undergoing dramatic changes. New cannabis products and new ways of using are emerging. These changes have the potential to affect exposure to cannabis smoke and other emissions from cannabis use. Cannabis smoke is known to contain fine, respirable particles (PM2.5) and other toxicants and carcinogens.Objectives: To assess the potential for exposure to PM2.5 from novel cannabis aerosols, we measured PM2.5 concentrations in a cannabis retail outlet (a dispensary) that permits on-site consumption of cannabis via non-combustion methods including vaporization and dabbing.Methods: PM2.5 concentrations in the dispensary were measured around the clock for five weeks using 2 laser photometer instruments (429,604 data points collected over 38.69 days). The instruments were calibrated gravimetrically using a controlled cigarette generation system at regular intervals during the experiment. Outdoor PM2.5 concentrations were taken from a nearby EPA monitoring station.Results: The average PM2.5 concentration in the dispensary retail space, during business hours, was 84 ± 124 µg/m3, with a median of 47 µg/m3. The average PM2.5 concentration when the business was closed was 3 ± 7 µg/m3 with a median of 2 µg/m3. The highest daily concentrations correlated with the hours with the most customers.Conclusion: Our results suggest that the use of cannabis products indoors, even by non-combustion methods, increases the concentration of PM2.5. These findings are of concern to the public health because the business studied was in compliance with local laws and because PM2.5 exposure is a known cause of cardiopulmonary and metabolic disease.

The gut microbiome composition is influenced by many factors including environmental exposures. Here, we investigated the effect of thirdhand cigarette smoke (THS) and exposure age on gut microbiome diversity. C57BL/6 mice were exposed to THS at human exposure relevant levels for three weeks during three different life stages: postnatal (0–3 weeks of age), pubescent (4–7 weeks of age), and adult (9–12 weeks of age), respectively. Cecal microbiome profiles were assessed at 17 weeks of age by 16S rRNA gene sequencing. We found that age at THS exposure strongly influenced the cecal microbiome composition. Although postnatal THS exposure significantly influenced the microbial composition, pubescent and adulthood exposures only had minor effects. The microbiome of postnatally THS‐exposed mice significantly increased several degradation pathways that regulate glycolysis and pyruvate decarboxylation, and significantly decreased coenzyme A biosynthesis and pyrimidine deoxyribonucleoside salvage. Our results indicate that mouse postnatal development is particularly susceptible to persistent THS exposure effects on the gut microbiome., Pollutants that are present in dust and remain on surfaces after tobacco has been smoked are collectively called thirdhand smoke (THS). When these pollutants are re‐emitted into the gas phase or react with other environmental chemicals, they have the potential to form secondary pollutants. We investigated the effect of THS exposure during three different life stages (postnatal, pubescent, and adult) on the gut microbiome in mice. Postnatal THS exposure significantly influenced the microbial composition, whereas pubescent and adulthood exposures only had minor effects.

Smoked cigarettes are the most prevalent form of litter worldwide, often finding their way into oceans and inland waterways. Cigarette smoke contains more than 4000 individual chemicals, some of them carcinogenic or otherwise toxic. We examined the cytotoxicity, genotoxicity, aryl hydrocarbon receptor (AhR), estrogen receptor (ER), and p53 response pathways of smoked cigarette leachate in vitro. Both seawater and freshwater leachates of smoked cigarettes were tested. Cytotoxicity and genotoxicity were negligible at 100 smoked cigarettes/L, while statistically significant AhR, ER, and p53 responses were observed in the extracts of both leachates, suggesting a potential risk to human health through exposure to cigarette litter in the environment. To identify responsible chemicals for the AhR response, an effect directed analysis approach was coupled with nontargeted chemical analysis based on comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC × GC/TOF-MS). Eleve...

Bei MRT-Untersuchungen sind Patienten einem sehr starken statischen Magnetfeld sowie energiereichen elektromagnetischen Wechselfeldern ausgesetzt. Dies kann bei Implantaten oder unabsichtlich in den Untersuchungsbereich gebrachten Gegenstanden mit magnetischen oder elektrisch leitfahigen Komponenten zu unerwunschten und gefahrlichen Effekten fuhren. In dieser Arbeit werden basierend auf bekannten physikalischen Gesetzmasigkeiten die wichtigsten Wechselwirkungsmechanismen zwischen den magnetischen und elektrischen Feldern bei der MRT mit Korpergewebe und korperfremden Materialien systematisch beschrieben. Die im Korper naturlicherweise vorkommenden Stoffe sind uberwiegend diamagnetisch und fuhren zu kaum wahrnehmbaren Kraftwirkungen in der MRT. Dagegen treten bei ferromagnetischen Stoffen wie Eisen am Eingangsbereich des Untersuchungstunnels Translationskrafte von mehr als dem Hundertfachen der Gewichtskraft auf. Auf langliche ferromagnetische Gegenstande wirken zusatzliche Drehmomente. Elektrisch gut leitfahige Materialien wie Metalle oder kohlefaserverstarkte Kunststoffe sind ebenfalls sicherheitsrelevant. Besonders in langen leitfahigen Strukturen, wie sie haufig in Implantaten vorkommen, konnen sich wahrend der MRT-Untersuchung starke Strome und an den Endstucken hohe elektrische Spannungen ausbilden. Die Hohe der elektrischen Spannungen an den Implantaten und die Stromdichte im angrenzenden Gewebe, das sich dabei stark erhitzen kann, sind im Einzelfall schwer vorhersehbar. Implantate, die ausgedehnte Ringstrome zulassen, zeigen oft deutliche Vibrationen durch Gradientenschaltungen. Auserdem treten an leitfahigen Platten oder Ringen merkliche Gegenkrafte auf, wenn sie im Magnetfeld schnell gekippt werden.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Thirdhand smoke (THS) is the residual tobacco contamination that remains after the smoke clears. We investigated the effects of THS exposure in utero and during early life in a transgenic Cdkn2a knockout mouse model that is vulnerable to the development of leukemia/lymphoma. Female mice, and their offspring, were exposed from the first day of pregnancy to weaning. Plasma cytokines, body weight and hematologic parameters were measured in the offspring. To investigate THS exposure effects on the development of leukemia/lymphoma, bone marrow (BM) was collected from control and THS-exposed mice and transplanted into BM-ablated recipient mice, which were followed for tumor development for 1 year. We found that in utero and early-life THS exposure caused significant changes in plasma cytokine concentrations and in immune cell populations; changes appeared more pronounced in male mice. Spleen (SP) and BM B-cell populations were significantly lower in THS-exposed mice. We furthermore observed that THS exposure increased the leukemia/lymphoma-free survival in BM transplantation recipient mice, potentially caused by THS-induced B-cell toxicity. A trend towards increased solid tumors in irradiated mice reconstituted with THS-exposed BM stimulates the hypothesis that the immunosuppressive effects of in utero and early-life THS exposure might contribute to carcinogenesis by lowering the host defense to other toxic exposures. Our study adds to expanding evidence that THS exposure alters the immune system and that in utero and early-life developmental periods represent vulnerable windows of susceptibility for these effects.

Thirdhand smoke (THS) is an environmental contaminant that may cause adverse health effects in smokers and nonsmokers. Currently, time-consuming analytical methods are necessary to assess chemicals in THS repositories, like upholstered furniture and clothing. Our goal was to develop a rapid, accessible method that can be used to measure THS contamination in common household fabrics and to evaluate remediation. Cotton, terry cloth, polyester, and wool were exposed to THS for various times in a controlled laboratory environment and then extracted in various media at room temperature or 60 °C to develop an autofluorescent method to quantify THS. Concentrations of nicotine and related alkaloids in the extracts were determined using liquid chromatography–tandem mass spectrometry (LC-MS/MS) and high-performance liquid chromatography (HPLC). The autofluorescence of extracts was proportional to the time and amount of THS exposure received by cotton and terry cloth. Extracts of polyester and wool did not show autofluorescence unless heat was applied during extraction. Nicotine, nicotine alkaloids, and TSNA concentrations were higher in THS extracts from cotton and terry cloth than extracts of polyester and wool carpet, in agreement with the autofluorescence data. For fabrics spiked with 10 mg of nicotine, extraction efficiency was much higher from terry cloth (7 mg) than polyester (0.11 mg). In high relative humidity, nicotine recovery from both cotton and polyester was 80% (~8 mg). Our results provide a simple, rapid method to assess THS contaminants in household fabrics and further show that THS extraction is influenced by fabric type, heat, and humidity. Thus, remediation of THS environments may need to vary depending on the fabric reservoirs being treated. Understanding the dynamics of THS in fabrics can help set up appropriate remediation policies to protect humans from exposure.

OCT angiography (OCT-A) allows non-invasive blood flow registration of the retina and choroid. In contrast to fluorescein angiography (FA), no dye has to be administered. The OCT-A also provides depth-selective information. OCT-A and FA were compared in patients with neovascular age-related macular degeneration (AMD) with retinal angiomatous proliferation (RAP) stage 1. In stage 1, the neovascularizations are intraretinal. In contrast to the two-dimensional total image of the FA, the OCT-A allows a depth-selective display of the individual retinal layers. In this way, a conclusion can be drawn about the place of origin of the RAP.Three patients with neovascular AMD and RAP stage 1 were included. They were examined with OCT (ZEISS CIRRUS HD-OCT 5000, Carl Zeiss Meditec, Inc., Dublin, USA), OCT-A (ZEISS AngioPlex OCT-Angiography) as well as FA (HRA2, Heidelberg Engineering) between January 2016 and March 2019. A complete ophthalmological examination was performed. A qualitative analysis of the OCT-A images (3 × 3 and 6 × 6 mm) and the FA images was carried out. Leaks in the FA were compared with the en-face images of the OCT-A followed by a depth-selective assignment using the corresponding B-scans of the OCT-A.It was one woman and two men aged 66 - 89 years. The visual acuity was 0.4 in the first, 0.5 p in the second and 0.8 in the third patient. The diagnosis of RAP stage 1 could be made both in the OCT, the FA and the OCT-A. All patients showed macular edema in the OCT. The FA showed selective hyperfluorescence in the early phase and fluorescein extravasation in the late phase. In OCT-A, the blood flow in all patients could be shown in the hyperreflective structure of the RAP in the B-scan. The first patient showed two RAP lesions in the FA, which were in the deep vascular plexus in the OCT-A. In the second patient, three RAP lesions were found in the FA, and a total of five RAP lesions in the OCT-A. One could be located in the superficial and deep vascular plexus, four in the deep vascular plexus. The third patient showed one RAP lesion in the FA as well as in the OCT-A, which could be assigned to the superficial vascular plexus.The OCT-A is well suited for the diagnosis of RAP stage 1. In the present cases, the diagnosis in the OCT-A could be made as clearly as by FA. A major advantage of the OCT-A results from the non-invasive character and the depth selectivity. The RAP 1 lesions could be assigned to both the superficial and the deep vascular plexus. Depth selection is not possible with the FA due to the summary picture.Die optische Kohärenztomografie-Angiografie (OCT-A) ermöglicht eine nicht invasive Blutflussregistrierung der Netzhaut und Aderhaut. Im Gegensatz zur Fluoresceinangiografie (FA) wird kein Farbstoff verabreicht. Die OCT-A liefert zusätzlich tiefenselektive Informationen. Bei Patienten mit neovaskulärer altersbezogener Makuladegeneration (AMD) mit retinalen angiomatösen Proliferationen (RAP) Stadium 1 wurden OCT-A und FA verglichen. Im Stadium 1 befinden sich die Neovaskularisationen intraretinal. Im Gegensatz zum 2-dimensionalen Summenbild der FA kann mithilfe der OCT-A eine tiefenselektive Darstellung der einzelnen Netzhautschichten erfolgen. Hierdurch kann ein Rückschluss auf den Entstehungsort der RAP gezogen werden.Es wurden 3 Patienten mit neovaskulärer AMD und RAP Stadium 1 eingeschlossen, die zwischen Januar 2016 und März 2019 sowohl mit OCT (ZEISS CIRRUS HD-OCT 5000, Carl Zeiss Meditec, Inc., Dublin, USA), OCT-A (ZEISS AngioPlex OCT-Angiografie) als auch FA (HRA2, Heidelberg Engineering) untersucht wurden. Es erfolgte eine komplette augenärztliche Untersuchung. Es wurde eine qualitative Analyse der OCT-A-Bilder (3 × 3 und 6 × 6 mm) und der FA-Bilder durchgeführt. Leckagen in der FA wurden mit den En-face-Aufnahmen der OCT-A verglichen. Anschließend erfolgte eine tiefenselektive Zuordnung anhand der entsprechenden B-Scans der OCT-A.Es handelte sich um eine Frau und 2 Männer im Alter zwischen 66 und 89 Jahren. Der Visus betrug 0,4 beim 1., 0,5 p beim 2. und 0,8 beim 3. Patienten. Die Diagnose einer RAP Stadium 1 konnte sowohl im OCT, mit der FA als auch mit der OCT-A gestellt werden. Bei allen Patienten zeigte sich in der OCT ein Makulaödem. In der FA zeigten sich punktuelle Hyperfluoreszenzen in der Frühphase und eine Fluoresceinextravasation in der Spätphase. In der OCT-A konnte im B-Scan der Blutfluss bei allen Patienten in der hyperreflektiven Struktur der RAP dargestellt werden. Bei dem 1. Patienten zeigten sich 2 RAP-Läsionen in der FA, die in der OCT-A im tiefen vaskulären Plexus lagen. Beim 2. Patienten fanden sich 3 RAP in der FA, in der OCT-A insgesamt 5 RAP-Läsionen. Eine konnte im oberflächlichen und tiefen vaskulären Plexus, 4 im tiefen vaskulären Plexus lokalisiert werden. Bei dem 3. Patienten zeigte sich eine RAP in der FA, ebenso wie in der OCT-A, die sich dem oberflächlichen vaskulären Plexus zuordnen ließ.Die OCT-A eignet sich gut zur Diagnostik einer RAP Stadium 1. In den vorliegenden Fällen konnte die Diagnose in der OCT-A ebenso eindeutig wie durch eine FA gestellt werden. Ein großer Vorteil der OCT-A ergibt sich durch den nicht invasiven Charakter und die Tiefenselektivität. Die RAP-1-Läsionen konnten sowohl dem superfiziellen als auch dem tiefen vaskulären Plexus zugeordnet werden. Eine Tiefenselektion ist mit der FA aufgrund des Summenbildes nicht möglich.

Introduction: Exposure to tobacco and marijuana smoke impairs vascular endothelial function. While the particulate phase of smoke is heavily implicated, the role of volatile constituents is unclear. Smoke contains aldehydes, which are known to cause endothelial dysfunction. We explored whether two aldehydes found in smoke, acrolein and acetaldehyde, can induce endothelial dysfunction. Hypothesis: Aldehydes in smoke impair endothelial function. Methods: We exposed 4 groups of anesthetized rats to 3 ppm acrolein and 10-11.5 ppm acetaldehyde gases (concentrations relevant to levels in secondhand smoke), Marlboro Red cigarette sidestream smoke at modest levels (600 μg/m 3 PM2.5) as a positive control, and clean air through the gas generation system as a negative control. Exposure was continuous for 10 minutes. Endothelial function (flow-mediated dilation; FMD) was quantified pre- and post-exposure by measuring femoral artery diameter with ultrasound before and after 5 min of transient ischemia and expressed as % vasodilation. Results: Impairment of FMD was observed for acrolein (10.8±1.7(SD)% vs. 5.8±2.9%, p=.001), acetaldehyde (8.8±2.0% vs. 6.0±2.5%, p=.001), and cigarette smoke (9.4±2.9% vs. 5.8±2.0%, p=.002), but not for air (7.9±2.0% vs. 9±3.2%, p=.44) (figure; each colored line denotes a rat pre- and post-exposure; bars denote means). Conclusions: Acrolein and acetaldehyde at levels found in secondhand smoke impair endothelial function. Our results suggest that despite a potential role of particles, volatile aldehydes may mediate part of the endothelial dysfunction caused by exposure to smoke.

Thirdhand cigarette smoke (THS) is a newly described toxin that lingers in the indoor environment long after cigarettes have been extinguished. Emerging results from both cellular and animal model studies suggest that THS is a potential human health hazard. DNA damage derived from THS exposure could have genotoxic consequences that would lead to development of diseases. However, THS exposure-induced interference with fundamental DNA transactions such as replication and transcription, and the role of DNA repair in ameliorating such effects, remain unexplored. Here we found that THS exposure increased the percentage of cells in S-phase, suggesting impaired S-phase progression. Key DNA damage response proteins including RPA, ATR, ATM, CHK1 and BRCA1 were activated in lung cells exposed to THS, consistent with replication stress. In addition, THS exposure caused increased 53BP1 foci, indicating DNA double-strand break (DSB) induction. Consistent with these results, we observed increased micronuclei formation, a marker of genomic instability, in THS-exposed cells. Exposure to THS also caused a significant increase in phosphorylated RNA Polymerase II engaged in transcription elongation, suggesting an increase in transcription-blocking lesions. In agreement with this conclusion, ongoing RNA synthesis was very significantly reduced by THS exposure. Loss of nucleotide excision repair (NER) exacerbated the reduction in RNA synthesis, suggesting that bulky DNA adducts formed by THS are blocks to transcription. The adverse impact on both replication and transcription supports genotoxic stress as a result of THS exposure, with important implications for both cancer and other diseases.

Introduction Thirdhand cigarette smoke is the fraction of cigarette smoke that remains in the environment long after a cigarette is extinguished. Methods The Truth Tobacco Industry Documents collection at the University of California San Francisco was searched for information on thirdhand smoke. Results In 1991, scientists at Philip Morris Inc conducted some of the first studies on thirdhand cigarette smoke. For 110 days, 8 hours a day, they ran sidestream cigarette smoke through a 30 m3 room that contained carpet, curtain, and textured wallpaper. The room was ventilated with clean air every night. By comparing the chemicals in the air during the 8-hour smoking period and during the clean air ventilation period, they showed that some smoke chemicals persist in the air 12 hours after smoking. By extracting the nicotine and nitrosamines from samples of the carpet, curtain, and wallpaper, they found that high concentrations of nicotine and the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) persisted in the room for more than 50 days; that surface chemistry affected nitrosamine concentrations; and that the concentration of NNK in the room, 110 days after the last cigarette was extinguished, could exceed the mass of NNK that entered the room as smoke. Conclusions These data, from a controlled environment where the total number of cigarettes smoked is known, provide further evidence that cigarette smoke chemicals remain in the environment for months after smoking, that they reemit back into the air, and that they react to form new toxins and carcinogens. Smoke-free policies are the best method to reduce exposure to thirdhand smoke. Implications This unpublished, original research from Philip Morris Inc demonstrates that majority of the nicotine and tobacco-specific nitrosamines in the secondhand smoke from each cigarette smoked indoors remains on indoor surfaces for months after the cigarette is extinguished. It also demonstrates that elevated concentrations of nicotine, ammonia, formaldehyde, and the gas-phase nitrosamine, N-nitrosopyrrolidine, can be found in the air for more than 12 hours after smoking; that surface chemistry affects nitrosamine formation and persistence; and that the amount of the carcinogenic nitrosamine NNK that persists months after smoking ends can exceed the amount that actually came out of the cigarettes.

© 2016 American Chemical Society. Thirdhand smoke (THS) is the contamination that persists after secondhand tobacco smoke has been emitted into air. It refers to the tobacco-related gases and particles that become embedded in materials, such as the carpet, walls, furniture, blankets, and toys. THS is not strictly smoke, but chemicals that adhere to surfaces from which they can be released back into the air, undergo chemical transformations and/or accumulate. Currently, the hazards of THS are not as well documented as the hazards of secondhand smoke (SHS). In this Perspective, we describe the distribution and chemical changes that occur as SHS is transformed into THS, studies of environmental contamination by THS, human exposure studies, toxicology studies using animal models and in vitro systems, possible approaches for avoiding exposure, remediation of THS contamination, and priorities for further research.

Smoked cigarettes are the most prevalent form of litter worldwide, often finding their way into oceans and inland waterways. Cigarette smoke contains more than 4000 individual chemicals, some of them carcinogenic or otherwise toxic. We examined the cytotoxicity, genotoxicity, aryl hydrocarbon receptor (AhR), estrogen receptor (ER), and p53 response pathways of smoked cigarette leachate

Background Electronic cigarettes (e-cigarettes) have experienced a tremendous increase in use. Unlike cigarette smoking, the effects of e-cigarettes and their constituents on mediating vascular health remain understudied. However, given their increasing popularity, it is imperative to evaluate the health risks of e-cigarettes, including the effects of their ingredients, especially nicotine and flavorings. Objectives The purpose of this study was to investigate the effects of flavored e-cigarette liquids (e-liquids) and serum isolated from e-cigarette users on endothelial health and endothelial cell–dependent macrophage activation. Methods Human-induced pluripotent stem cell–derived endothelial cells (iPSC-ECs) and a high-throughput screening approach were used to assess endothelial integrity following exposure to 6 different e-liquids with varying nicotine concentrations and to serum from e-cigarette users. Results The cytotoxicity of the e-liquids varied considerably, with the cinnamon-flavored product being most potent and leading to significantly decreased cell viability, increased reactive oxygen species (ROS) levels, caspase 3/7 activity, and low-density lipoprotein uptake, activation of oxidative stress-related pathway, and impaired tube formation and migration, confirming endothelial dysfunction. Upon exposure of ECs to e-liquid, conditioned media induced macrophage polarization into a pro-inflammatory state, eliciting the production of interleukin-1β and -6, leading to increased ROS. After exposure of human iPSC-ECs to serum of e-cigarette users, increased ROS linked to endothelial dysfunction was observed, as indicated by impaired pro-angiogenic properties. There was also an observed increase in inflammatory cytokine expression in the serum of e-cigarette users. Conclusions Acute exposure to flavored e-liquids or e-cigarette use exacerbates endothelial dysfunction, which often precedes cardiovascular diseases.

Patients undergoing MRI examinations are exposed to a strong static magnetic field and powerful electromagnetic alternating fields. Undesired or even dangerous effects could be caused if implants or objects with magnetic or electrically conductive elements are accidentally brought into the examination area.Relevant interactions in MRI between magnetic/electric fields and body tissue as well as foreign materials are systematically presented, based on proven physical principles.Natural components of the human body are mainly diamagnetic leading to only hardly perceptible magnetic forces in MRI. In contrast, ferromagnetic items as iron show translational forces of more than hundred times their weight force when brought to the entry of the bore. Lengthy ferromagnetic items are additionally subjected to torque. Materials with high electrical conductivity as metals and carbon fibre-reinforced plastic are also safety relevant. Especially long conductive structures as often present in implants are prone to induced strong electrical currents and high voltages at their end portions. Maximum voltages occurring at the implants and current density in adjacent tissue which might cause significant heating are hardly predictable for individual cases. Implants providing extended conductive loops for ring currents often show strong vibrations due to gradient switching. Counter forces must be considered when tilting conductive plates or ring structures inside the magnetic field area.

Although substantial evidence shows that smoking is positively and robustly associated with cardiovascular disease (CVD), the CVD risk associated with the use of new and emerging tobacco products, such as electronic cigarettes, hookah, and heat-not-burn products, remains unclear. This uncertainty stems from lack of knowledge on how the use of these products affects cardiovascular health. Cardiovascular injury associated with the use of new tobacco products could be evaluated by measuring changes in biomarkers of cardiovascular harm that are sensitive to the use of combustible cigarettes. Such cardiovascular injury could be indexed at several levels. Preclinical changes contributing to the pathogenesis of disease could be monitored by measuring changes in systemic inflammation and oxidative stress, organ-specific dysfunctions could be gauged by measuring endothelial function (flow-mediated dilation), platelet aggregation, and arterial stiffness, and organ-specific injury could be evaluated by measuring endothelial microparticles and platelet-leukocyte aggregates. Classical risk factors, such as blood pressure, circulating lipoproteins, and insulin resistance, provide robust estimates of risk, and subclinical disease progression could be followed by measuring coronary artery Ca2+ and carotid intima-media thickness. Given that several of these biomarkers are well-established predictors of major cardiovascular events, the association of these biomarkers with the use of new and emerging tobacco products could be indicative of both individual and population-level CVD risk associated with the use of these products. Differential effects of tobacco products (conventional vs. new and emerging products) on different indexes of cardiovascular injury could also provide insights into mechanisms by which they induce cardiovascular harm.

This report provides an overview on the present knowledge on intramyocellular lipids (IMCL) and their dynamics in the course of interventions with physical activity of variable type and intensity in different population groups, as accessible by examinations using non-invasive volume-selective 1 H magnetic resonance spectroscopy (1 H MRS). IMCL serve as energy source in skeletal muscle for fat oxidation in the mitochondria and became intensively studied after discovery of their relation with insulin sensitivity. While baseline levels of IMCL concentration have been shown to be mainly dependent on the metabolic status (insulin sensitivity), on the level of training and on fibre composition in the muscles, studies applying different physical activity protocols revealed the dynamic of their depletion and replenishment. From the findings in human studies, it can be concluded that IMCL levels are potentially useful markers for monitoring metabolic adaptation of skeletal muscle to sportive activities and training.

© 2018 the American Physiological Society and American Physiological Society. All rights reserved. Evidence is accumulating that exposure to cigarette smoke (CS) increases the risk of developing acute respiratory distress syndrome (ARDS). Streptococcus pneumoniae is the most common cause of bacterial pneumonia, which in turn is the leading cause of ARDS. Chronic smokers have increased rates of pneumococcal colonization and develop more severe pneumococcal pneumonia than nonsmokers; yet mechanistic connections between CS exposure, bacterial pneumonia, and ARDS pathogenesis remain relatively unexplored. We exposed mice to 3 wk of moderate whole body CS or air, followed by intranasal inoculation with an invasive serotype of S. pneumoniae. CS exposure alone caused no detectable lung injury or bronchoalveolar lavage (BAL) inflammation. During pneumococcal infection, CS-exposed mice had greater survival than air-exposed mice, in association with reduced systemic spread of bacteria from the lungs. However, when mice were treated with antibiotics after infection to improve clinical relevance, the survival benefit was lost, and CS-exposed mice had more pulmonary edema, increased numbers of BAL monocytes, and elevated monocyte and lymphocyte chemokines. CS-exposed antibiotic-treated mice also had higher serum surfactant protein D and angiopoietin-2, consistent with more severe lung epithelial and endothelial injury. The results indicate that acute CS exposure enhances the recruitment of immune cells to the lung during bacterial pneumonia, an effect that may provide microbiological benefit but simultaneously exposes the mice to more severe inflammatory lung injury. The inclusion of antibiotic treatment in preclinical studies of acute lung injury in bacterial pneumonia may enhance clinical relevance, particularly for future studies of current or emerging tobacco products.

Exposure to thirdhand smoke (THS) is a recently described health concern that arises in many indoor environments. However, the carcinogenic potential of THS, a critical consideration in risk assessment, remains untested. Here we investigated the effects of short-term early exposure to THS on lung carcinogenesis in A/J mice. Forty weeks after THS exposure from 4 to 7 weeks of age, the mice had increased incidence of lung adenocarcinoma, tumor size and, multiplicity, compared with controls. In vitro studies using cultured human lung cancer cells showed that THS exposure induced DNA double-strand breaks and increased cell proliferation and colony formation. RNA sequencing analysis revealed that THS exposure induced endoplasmic reticulum stress and activated p53 signaling. Activation of the p53 pathway was confirmed by an increase in its targets p21 and BAX. These data indicate that early exposure to THS is associated with increased lung cancer risk.

Thirdhand smoke (THS) is the fraction of cigarette smoke that persists in indoor environments after smoking. We investigated the effects of neonatal and adult THS exposure on bodyweight and blood cell populations in C57BL/6 J mice. At the end of neonatal exposure, THS-treated male and female mice had significantly lower bodyweight than their respective control mice. However, five weeks after neonatal exposure ended, THS-treated mice weighed the same as controls. In contrast, adult THS exposure did not change bodyweight of mice. On the other hand, both neonatal and adult THS exposure had profound effects on the hematopoietic system. Fourteen weeks after neonatal THS exposure ended, eosinophil number and platelet volume were significantly higher, while hematocrit, mean cell volume, and platelet counts were significantly lower compared to control. Similarly, adult THS exposure also decreased platelet counts and increased neutrophil counts. Moreover, both neonatal and adult THS exposure caused a significant increase in percentage of B-cells and significantly decreased percentage of myeloid cells. Our results demonstrate that neonatal THS exposure decreases bodyweight and that THS exposure induces persistent changes in the hematopoietic system independent of age at exposure. These results also suggest that THS exposure may have adverse effects on human health.

Accurate and reliable measurements of exposure to tobacco products are essential for identifying and confirming patterns of tobacco product use and for assessing their potential biological effects in both human populations and experimental systems. Due to the introduction of new tobacco-derived products and the development of novel ways to modify and use conventional tobacco products, precise and specific assessments of exposure to tobacco are now more important than ever. Biomarkers that were developed and validated to measure exposure to cigarettes are being evaluated to assess their use for measuring exposure to these new products. Here, we review current methods for measuring exposure to new and emerging tobacco products, such as electronic cigarettes, little cigars, water pipes, and cigarillos. Rigorously validated biomarkers specific to these new products have not yet been identified. Here, we discuss the strengths and limitations of current approaches, including whether they provide reliable exposure estimates for new and emerging products. We provide specific guidance for choosing practical and economical biomarkers for different study designs and experimental conditions. Our goal is to help both new and experienced investigators measure exposure to tobacco products accurately and avoid common experimental errors. With the identification of the capacity gaps in biomarker research on new and emerging tobacco products, we hope to provide researchers, policymakers, and funding agencies with a clear action plan for conducting and promoting research on the patterns of use and health effects of these products.

Key Points Question Does acute inhalation of thirdhand smoke alter the transcriptome of the human nasal epithelium? Findings This randomized clinical trial exposed 4 healthy, nonsmoking women to clean air, which altered the expression of only 2 genes. When the same women were exposed to thirdhand smoke at least 21 days later, 389 genes associated with cell stress and survival pathways were differentially expressed, and many affected genes were associated with increased mitochondrial activity, oxidative stress, DNA repair, cell survival, and inhibition of cell death. Meaning These results suggest that acute exposure to thirdhand smoke stresses the human nasal epithelium, a finding that may be valuable to physicians treating exposed patients., This randomized clinical trial compares changes in the transcriptome of the human nasal epithelium in healthy, nonsmoking women who were first exposed to clean air and later exposed to thirdhand smoke., 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.

Exposure to thirdhand smoke (THS) is a newly described health risk. Evidence supports its widespread presence in indoor environments. However, its genotoxic potential, a critical aspect in risk assessment, is virtually untested. An important characteristic of THS is its ability to undergo chemical transformations during aging periods, as demonstrated in a recent study showing that sorbed nicotine reacts with the indoor pollutant nitrous acid (HONO) to form tobacco-specific nitrosamines (TSNAs) such as 4-(methylnitrosamino)-4-(3-pyridyl)butanal (NNA) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The goal of this study was to assess the genotoxicity of THS in human cell lines using two in vitro assays. THS was generated in laboratory systems that simulated short (acute)- and long (chronic)-term exposures. Analysis by liquid chromatography-tandem mass spectrometry quantified TSNAs and common tobacco alkaloids in extracts of THS that had sorbed onto cellulose substrates. Exposure of human HepG2 cells to either acute or chronic THS for 24h resulted in significant increases in DNA strand breaks in the alkaline Comet assay. Cell cultures exposed to NNA alone showed significantly higher levels of DNA damage in the same assay. NNA is absent in freshly emitted secondhand smoke, but it is the main TSNA formed in THS when nicotine reacts with HONO long after smoking takes place. The long amplicon-quantitative PCR assay quantified significantly higher levels of oxidative DNA damage in hypoxanthine phosphoribosyltransferase 1 (HPRT) and polymerase β (POLB) genes of cultured human cells exposed to chronic THS for 24h compared with untreated cells, suggesting that THS exposure is related to increased oxidative stress and could be an important contributing factor in THS-mediated toxicity. The findings of this study demonstrate for the first time that exposure to THS is genotoxic in human cell lines.

Thirdhand cigarette smoke (THS) was recently recognized as an environmental health hazard; however, little is known about it effects on cells. Mitochondria are sensitive monitors of cell health and report on environmentally induced stress. We tested the effects of low levels of THS extracted from terry cloth on mitochondrial morphology and function using stem cells with well-defined mitochondria. Concentrations of THS that did not kill cells caused stress-induced mitochondrial hyperfusion (SIMH), which was characterized by changes in mitochondrial morphology indicative of fusion, increased mitochondrial membrane potential (MMP), increased ATP levels, increased superoxide production, and increased oxidation of mitochondrial proteins. SIMH was accompanied by a decrease in Fis1 expression, a gene responsible for mitochondrial fission, and a decrease in apoptosis-related genes, including Aifm2, Bbc3, and Bid There was also down regulation of Ucp2, Ucp4, and Ucp5, genes that decrease MMP thereby reducing oxidative phosphorylation, while promoting glycolysis. These effects, which collectively accompany SIMH, are a prosurvival mechanism to rescue damaged mitochondria and protect cells from apoptosis. Prolonged exposure to THS caused a reduction in MMP and decreased cell proliferation, which likely leads to apoptosis.