Smoking Markers Research Articles

DNA methylation at AHRR as a master predictor of smoke exposure and a biomarker for sleep and exercise

BackgroundDNA methylation profiling may provide a more accurate measure of the smoking status than self-report and may be useful in guiding clinical interventions and forensic investigations. In the current study, blood DNA methylation profiles of nearly 800 Polish individuals were assayed using Illuminia EPIC and the inference of smoking from epigenetic data was explored. In addition, we focused on the role of the AHRR gene as a top marker for smoking and investigated its responsiveness to other lifestyle behaviors.ResultsWe found > 450 significant CpGs associated with cigarette consumption, and overrepresented in various biological functions including cell communication, response to stress, blood vessel development, cell death, and atherosclerosis. The model consisting of cg05575921 in AHRR (p = 4.5 × 10–32) and three additional CpGs (cg09594361, cg21322436 in CNTNAP2 and cg09842685) was able to predict smoking status with a high accuracy of AUC = 0.8 in the test set. Importantly, a gradual increase in the probability of smoking was observed, starting from occasional smokers to regular heavy smokers. Furthermore, former smokers displayed the intermediate DNA methylation profiles compared to current and never smokers, and thus our results indicate the potential reversibility of DNA methylation after smoking cessation. The AHRR played a key role in a predictive analysis, explaining 21.5% of the variation in smoking. In addition, the AHRR methylation was analyzed for association with other modifiable lifestyle factors, and showed significance for sleep and physical activity. We also showed that the epigenetic score for smoking was significantly correlated with most of the epigenetic clocks tested, except for two first-generation clocks.ConclusionsOur study suggests that a more rapid return to never-smoker methylation levels after smoking cessation may be achievable in people who change their lifestyle in terms of physical activity and sleep duration. As cigarette smoking has been implicated in the literature as a leading cause of epigenetic aging and AHRR appears to be modifiable by multiple exogenous factors, it emerges as a promising target for intervention and investment.

Measuring air quality in smoking and nonsmoking areas of Nevada casinos (Reno/Sparks): Potential exposure of minors to secondhand smoke.

To understand the potential exposure to tobacco smoke in Washoe County (Reno/Sparks), Nevada casinos by measuring air quality in smoking areas relative to non-smoking/non-gaming areas in which minors may be present. To act as a pilot study in community-based health research and policy campaigns by evaluating low-cost air monitors to measure personal secondhand smoke (SHS) exposure. We used customized mobile apps, AtmoTube PRO Air Monitors, and hand clickers to measure the timing and minute-by-minute levels of PM2.5 (a tobacco smoke marker). The app was used to record the number of smokers, minors, and total patrons associated with ~10-minute sequential time periods in standardized casino locations, including outdoor areas, slots, tables, restaurants, bars/lounges, arcades, among others. Between April and May 2022, we successfully visited 14 casinos and 18 distinct types of indoor casino locations. We found high PM2.5 peaks in casino locations even with zero, or a low percentage of, observed active smokers, including in both gaming/non-gaming areas. Indoor areas, regardless of smoking/non-smoking areas, consistently had higher PM2.5 levels than outdoor background levels. Indoor locations had median PM2.5 levels up to 18 times higher than the lowest outdoor background levels. Minors were present throughout all casino locations, and thus were likely exposed to elevated PM2.5 levels. Potential PM2.5 exposures due to smoking can be high regardless of ventilation systems. Small proportions of smokers in a location can lead to high levels of exposure. Establishing comprehensive smoke-free casinos is the only way to protect against SHS harms.

Carboxyethylsilanetriol-Coated Magnetic Nanoparticles as an Ultrasensitive Immunoplatform for Electrochemical Magnetosensing of Cotinine.

In the present study, an innovative and simple electrochemical magneto biosensor based on carboxyethylsilanetriol-modified iron oxide (Fe3O4) magnetic nanoparticles was designed for ultrasensitive and specific analysis of cotinine, an important marker of smoking. Anticotinine antibodies were covalently immobilized on carboxylic acid-modified magnetic nanoparticles, and the cotinine-specific magnetic nanoparticles created a specific surface on the working electrode surface. The use of magnetic nanoparticles as an immobilization platform for antibodies provided a large surface area for antibody attachment and increased sensitivity. In addition, the advantages of the new immobilization platform were reusing the working electrode numerous times, recording repeatable and reproducible signals, and reducing the necessary volume of biomolecules. The specific interaction between cotinine and cotinine-specific antibody-attached magnetic nanoparticles restricted the electron transfer of the redox probe and changed the impedimetric response of the electrode correlated to the concentration of cotinine. The magneto biosensor had a wide detection range (2-300 pg/mL), a low LOD (606 fg/mL), and an acceptable recovery (97.24-105.31%) in real samples. In addition, the current biosensor's measurement results were in good agreement with those found by the standard liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA) methods. These results showed that a simple impedimetric immunosensing platform was generated for the cotinine analysis.

Deficient sleep, altered hypothalamic functional connectivity, depression and anxiety in cigarette smokers

BackgroundDeficient sleep is implicated in nicotine dependence as well as depressive and anxiety disorders. The hypothalamus regulates the sleep-wake cycle and supports motivated behavior, and hypothalamic dysfunction may underpin comorbid nicotine dependence, depression and anxiety. We aimed to investigate whether and how the resting state functional connectivities (rsFCs) of the hypothalamus relate to cigarette smoking, deficient sleep, depression and anxiety. MethodsWe used the data of 64 smokers and 198 age- and sex-matched adults who never smoked, curated from the Human Connectome Project. Deficient sleep and psychiatric problems were each assessed with Pittsburgh Sleep Quality Index (PSQI) and Achenbach Adult Self-Report. We processed the imaging data with published routines and evaluated the results at a corrected threshold, all with age, sex, and the severity of alcohol use as covariates. ResultsSmokers vs. never smokers showed poorer sleep quality and greater severity of depression and anxiety. In smokers only, the total PSQI score, indicating more sleep deficits, was positively associated with hypothalamic rsFCs with the right inferior frontal/insula/superior temporal and postcentral (rPoCG) gyri. Stronger hypothalamus-rPoCG rsFCs were also associated with greater severity of depression and anxiety in smokers but not never smokers. Additionally, in smokers, the PSQI score completely mediated the relationships of hypothalamus-rPoCG rsFCs with depression and anxiety severity. ConclusionsThese findings associate hypothalamic circuit dysfunction to sleep deficiency and severity of depression and anxiety symptoms in adults who smoke. Future studies may investigate the roles of the hypothalamic circuit in motivated behaviors to better characterize the inter-related neural markers of smoking, deficient sleep, depression and anxiety.

Vital exhaustion as a marker of chronic social stress and smoking among people aged 25-44 years

Aim. To analyze the associations of exhaustion, as a marker of chronic social stress, with smoking in a random representative sample of people aged 25-44 years in Novosibirsk.Material and methods. In Research Institute of Internal and Preventive Medicine — branch of the Institute of Cytology and Genetics, in 2013-2016, a study of a random representative sample of people aged 25-44 years in one of the Novosibirsk districts was conducted (registration № FWNR-2024-0002). A total of 975 individuals were examined, of which 427 men and 548 women. The response rate was >70%. Assessment of exhaustion level and attitude towards smoking was carried out according to standard methods of the World Health Organization's MONICA-psychosocial (MOPSY) program protocol.Results. Among people aged 25-44 years, 38,3% of men and 56,1% of women had exhaustion (χ2=40,744; df=2, p<0,001). Among people of both sexes aged 25-44 years, 58,9% were smokers, of which 27,1% stopped smoking, while 31,8% continued to smoke. Among men, 72,7% smoked, 29% stopped smoking and 43,7% continued smoking. Among women, 48,4% smoked, 25,6% stopped smoking, and 22,8% continued smoking (χ2=72,374; df=5, p<0,001). Among people of both sexes aged 25-44 years with a high exhaustion, 10,5% tried to change their smoking status, but unsuccessfully (χ2=20,708; df=10, p<0,05), and among women — 7,2% (χ2=27,117; df=10, p<0,05). Among those who tried unsuccessfully to change their smoking status (10,1%), "some events annoyed more now than before" (χ2=20,053; df=10, p<0,05). Women who smoke (33%), as well as women who smoke but quit for a while (21,2%) "wanted to die at times" (χ2=20,040; df=10, p<0,05). Among those who smoke, but quit for some time, both among people of both sexes 25-44 years old (14,7%) (χ2=22,783; df=10, p<0,05) and among men (16,1%) (χ2=19,593; df=10, p<0,05) and women (14%) (χ2=20,734; df=10, p<0,05) individually, more often "there was a feeling that recently life requires more strength than is left." Men who tried unsuccessfully to change their smoking status were (13,8%) more often "woke up feeling exhausted and tired" (χ2=19,713; df=10, p<0,05).Conclusion. We found that people with a high exhaustion have greater dependence on smoking.

Waterpipe and cigarette epigenome analysis reveals markers implicated in addiction and smoking type inference

Waterpipe smoking is frequent in the Middle East and Africa with emerging prevalence worldwide. The epigenome acts as a molecular sensor to exposures and a crucial driver in several diseases. With the widespread use of waterpipe smoking, it is timely to investigate its epigenomic markers and their role in addiction, as a central player in disease prevention and therapeutic strategies. DNA methylome-wide profiling was performed on an exposure-rich population from the Middle East, constituting of 216 blood samples split equally between never, cigarette-only and waterpipe-only smokers. Waterpipe smokers showed predominantly distinct epigenetic markers from cigarette smokers, even though both smoking forms are tobacco-based. Moreover, each smoking form could be accurately (∼90 %) inferred from the DNA methylome using machine learning. Top markers showed dose–response relationship with extent of smoking and were validated using independent technologies and additional samples (total N = 284). Smoking markers were enriched in regulatory regions and several biological pathways, primarily addiction. The epigenetically altered genes were not associated with genetic etiology of tobacco use, and the methylation levels of addiction genes, in particular, were more likely to reverse after smoking cessation. In contrast, other epigenetic markers continued to feature smoking exposure after cessation, which may explain long-term health effects observed in former smokers. This study reports, for the first time, blood epigenome-wide markers of waterpipe smokers and reveals new markers of cigarette smoking, with implications in mechanisms of addiction and the capacity to discriminate between different smoking types. These markers may offer actionable targets to reverse the epigenetic memory of addiction and can guide future prevention strategies for tobacco smoking as the most preventable cause of illnesses worldwide.

Association of Dietary Flavonoid Intake with Serum Cotinine Levels in the General Adult Population.

Cotinine, the primary metabolite of nicotine, can be utilized as a marker for active smoking and as an indicator of exposure to secondhand smoke. However, the direct relationship between dietary flavonoid intake and serum cotinine levels remains a subject of ongoing investigation. In this study, we utilized data from the National Health and Nutrition Examination Survey (NHANES) 2007-2010 and 2017-2018 to assess the association between dietary flavonoid intake and serum cotinine levels in adults through multiple linear regression analysis. A weighted quantile sum (WQS) regression model was used to assess the association of the mixture of six dietary flavonoids with serum cotinine levels in adults, which could represent the overall effect of the mixture of six dietary flavonoids. We also conducted stratified analyses by smoke status to explore multiple linear regression associations between different flavonoid intake and serum cotinine levels. A total of 14,962 adults were included in the study. Compared to the group with the lowest dietary flavonoid intake, total flavonoid intake in the second (β = -0.29 [-0.44, -0.14]), third (β = -0.41 [-0.58, -0.24]), and highest groups (β = -0.32 [-0.49, -0.16]) was inversely related to the levels of serum cotinine after adjusting the full model. An RCS model showed that when the total dietary flavonoid intake was less than 99.61 mg/day, there was a negative linear association between dietary flavonoid intake and the serum cotinine. The WQS regression model also showed that the intake of a mixture of six dietary flavonoids was significantly negatively correlated with serum cotinine levels (β = -0.54 [-0.61, -0.46], p <0.01), with anthocyanins having the greatest effect (weights = 32.30%). Our findings imply a significant correlation between dietary flavonoid intake and serum cotinine levels among adults. The consumption of a combination of six dietary flavonoids was consistently linked to lower serum cotinine levels, with anthocyanins displaying the most pronounced impact.

Secondary Bladder Cancer After Prostate Cancer Treatment: An Age-matched Comparison Between Radiation and Surgery

BackgroundSecondary malignancy is a long-term risk of radiation. External beam radiation therapy (EBRT) for prostate cancer treatment has been associated with later development of bladder cancer and worse bladder cancer features. ObjectiveWe sought to provide an updated comparison of the long-term risk of bladder cancer after different localized prostate cancer treatments. Design, setting, and participantsUsing the Surveillance, Epidemiology, and End Results (SEER) cancer registry, we compared an age-matched subset of patients who underwent radical prostatectomy (RP) with those who underwent EBRT, brachytherapy (BT), EBRT + BT, and RP followed by EBRT (RPtoEBRT) between 2000 and 2018. Our final cohort included 261 609 patients with a median follow-up of 11.6 yr. Outcome measurements and statistical analysisOur primary outcomes were time to bladder cancer diagnosis, muscle-invasive bladder cancer diagnosis, and bladder cancer death. We used cause-specific hazard models considering death as a competing event. A similar analysis was performed on lung cancer, as a surrogate marker for smoking. We also compared proportions of variant histology, high-grade, and invasive disease among bladder cancers that occurred after radiation versus RP using chi-square testing. Results and limitationsAll radiation groups were associated with bladder cancer diagnosis; hazard ratios (HRs) were 1.72, 1.85, 1.80, and 1.53 for EBRT, BT, EBRT + BT, and RPtoEBRT, respectively, using RP as a referent (all p < 0.001). HRs for bladder cancer death were even higher: 2.39, 2.57, and 3.02 for EBRT, BT, and EBRT + BT, respectively (all p < 0.001), except for RPtoEBRT (HR 1.43, p = 0.28). Lung cancer diagnosis was also associated with radiation but at lower HRs—1.63, 1.32, 1.42, and 1.30 for EBRT, BT, EBRT + BT, and RPtoEBRT, respectively (all p < 0.001). There were a higher proportion of ≥T2, ≥T3, and sarcomatoid variant bladder cancers after radiation (all p < 0.01) ConclusionsThe risk of developing and dying from bladder cancer is increased in patients treated with radiation compared with those treated with RP. The risk was similar for BT and EBRT. Bladder cancers after radiation are more likely to be sarcomatoid variant and present as muscle invasive. Patient summaryWe observed the rates of bladder cancer after patients had undergone surgery or radiation for prostate cancer, and found higher rates of bladder cancer after radiation. We also observed that bladder cancers that occur after radiation tend to be more aggressive.

Association between cadmium and lead in active and passive cigarette smokers with bone mass: a retrospective study

Objective: Cigarette smoking harms all body systems, and its effects are primarily related to nicotine. However, the heavy metal content (mainly lead and cadmium) could add to nicotine's hazardous effects. Thus, the current study aimed to investigate the effect of cigarette smoking content of cadmium and lead on bone mineral density. Subjects and Methods: A retrospective analysis of data from active, passive, and non-smokers (every 70 subjects) was analyzed for patient demographics, laboratory investigation, serum cotinine (as a confirmatory marker of smoking, bone mineral density (BMD), blood and urinary levels of cadmium and lead). Results: Hemoglobin concentrations and red blood cell count were significantly reduced, while erythrocyte sedimentation rate and liver enzymes were significantly increased in active and passive smokers than non-smokers. Serum cadmium, lead, and cotinine were raised considerably in passive and active than non-smokers (0.47±0.05, 21.94±3.99, 5.35±0.90 in active, 0.32±0.09, 18.91±3.30, and 4.35±0.89 in passive, versus 0.09±0.06, 9.84±2.63, and 1.28±0.21 in the control group, successively). Bone mineral density was reduced in active and passive than non-smokers at the radial shaft, femoral neck, and spine. Cotinine was significantly and proportionately correlated with serum cadmium and lead and inversely correlated with bone mineral density. Furthermore, cadmium and lead were inversely correlated with BMD. Conclusion: Cigarettesmoke was associated with higher concentrations of cadmium, and lead may directly and indirectly share in the harmful effects of smoking on BMD. Keywords: Bone Mineral Density, Cotinine, Toxic Heavy Metals, Smoking

Modelling Smoke Flavour in Wine from Chemical Composition of Smoke-Exposed Grapes and Wine

Wine grapes exposed to smoke and wine made from grapes exposed to smoke can robustly be identified through their elevated concentrations of volatile phenols and phenolic glycosides serving as smoke markers, compared to concentrations typically found in non-smoke-exposed samples. Smoke-affected wines with high concentrations of volatile phenols and glycosides can have smoky flavours, but the relationship between concentrations of specific smoke markers in grapes and the intensity of smoky sensory attributes in the resulting wine has not been established. This study sought to determine whether volatile phenols and glycoside concentration in grapes and wine are suited to predict smoke flavour, to identify the key drivers of smoke flavour in both matrices. The study aimed to determine what concentrations of volatiles and glycosides in grapes impart an unacceptable smoke flavour in the resulting wine, to provide a guide for producers assessing suitability of smoke-exposed grapes for wine production. During vintage 2020, a total of 65 grape samples were collected from vineyards exposed to bushfire smoke, as well as unaffected vineyards. Chardonnay, Pinot Noir, and Shiraz grapes were harvested from vineyards in New South Wales, South Australia, and Victoria. Unoaked wines (50 kg scale) were produced under controlled conditions. The wines had a wide range of smoke flavour intensities rated by a trained sensory panel. Statistical models based on guaiacol, o-cresol, m-cresol, p-cresol, and some glycosides gave good predictions of smoke flavour intensity, with a slightly different optimal model for each cultivar. Subsequently, critical concentrations for quality defects were estimated to provide a guide for producers. A subset of smoke exposure markers in wine grapes affected by smoke from bushfires can be used to predict the degree of smoke flavour in wine. This information provides a first guide for assessing the risk of producing smoke tainted wine from smoke-exposed grapes.

Cotinine as a Sentinel of Canine Exposure to Tobacco Smoke.

The adverse health effects of both active and passive tobacco smoke have been well-known in humans for a long time. It is presumable that even pets, which intimately share the owner's lifestyle, may be exposed to the same risks. This study aimed to detect and quantify cotinine (a metabolite of nicotine) in the serum and hair of dogs using a specific commercial ELISA immunoassay kit. A total of 32 dogs, 16 exposed and 16 unexposed to the owner's smoke, were enrolled. The cotinine concentration was higher in the exposed than the unexposed group in both matrices (p < 0.001), with greater values in serum than in hair (p < 0.001). Exposed bitches had higher hair cotinine than male dogs (p < 0.001). Conversely, serum and fur cotinine concentrations were lower in female than male dogs of the unexposed group (p < 0.01). The exposure intensity, age, and weight of the dogs did not affect cotinine concentrations. A cut-off value of 2.78 ng/mL and 1.13 ng/mL cotinine concentration in serum and fur, respectively, was estimated to distinguish between the exposed and unexposed dogs. Cotinine was confirmed as a valuable marker of passive smoking also in dogs. Although owners do not perceive secondhand smoke as a risk for their dogs, greater awareness should be advisable, especially in pregnant animals.

Grape smoke exposure risk assessment: Wine matrix impact on smoke marker compound smoke expression

During wildfires large amounts of volatile phenols (VP’s) are released into the air from wood burning. These compounds absorb through the berry skin, where they are quickly glycosylated. Studies have shown that both the free and bound volatile phenols contribute to smoke taint perception. For grape smoke exposure risk assessment, both the natural amount of free and bound VP’s in grapes (baseline) as well as rejection threshold levels of these compounds in different wine matrixes need to be determined. In the current study the sensory attributes of different smoke impacted and non-smoke impacted wines from the same sites were determined by descriptive analysis. Multivariate statistics were used to relate smoke-related sensory attributes to smoke marker compounds. Subsequently, wines with different levels of smoke marker compounds were made by serial dilution of a smoke impacted wine with its respective non-impacted wine. A consumer study was conducted to determine the change in ‘liking’ for a wine depending on the percentage inclusion of smoke impacted wine. Rejection threshold levels of smoke marker compounds in red wine matrixes were determined by linking ‘liking’ scores to specific wine attributes. This is the first step in creating clear guidelines for wine smoke taint risk assessment.

Formation of secondary organic material from gaseous precursors in wood smoke

ABSTRACT The apportionment of the contribution of wood smoke emitted particles to the total concentration of particulate matter in a region has been greatly aided by the development of new analytical methods. These analytical methods quantitatively determine organic marker compounds unique to wood combustion such as levoglucosan and dehydroabietic acid. These markers have generally been determined in 24-hour averaged samples. We have developed an instrument based on the collection of particles on an inert filter, desorption of the organic material in an inert atmosphere with subsequent GC separation and MS detection of the desorbed compounds. The GC-MS Organic Aerosol Monitor (OAM) instrument has been used in three field studies. An unexpected finding from these studies was the quantification of the contribution of secondary organic aerosols from gases present in wood smoke in addition to primary wood smoke emitted particles. The identification of this secondary material was made possible by the collection of hourly averaged data that allowed for the time patterns of black carbon, organic material, and wood smoke marker compounds to be included and compared in a Positive Matrix Factorization (PMF) analysis. Most of the organic markers associated with wood smoke (levoglucosan, stearic acid and dehydroabietic acid) are associated with primary wood smoke emissions, but a fraction of the levoglucosan and stearic acid are also associated with secondary organic material formed from gaseous precursors in wood smoke. Additionally, this secondary material was shown to be present in each in of the three urban area where wood smoke burning occurs. There is a need for additional studies to better understand the contribution of secondary particulate formation from both urban and wildfires. Implications: This paper presents results from three field studies which show that in addition to the formation of primary particulate matter from the combustion of wood smoke and secondary particulate matter is also formed from the gaseous compounds emitted with the wood smoke. This material is identified in the studies of wood combustion reported here by the identification and quantification of specific organic marker compounds related to wood combustion and is shown to and represents a contributor nearly as large as the primary emitted material and better quantifying the impact of wood combustion on airborne fine particulate matter.

Difficulties in emotion regulation and ad libitum smoking topography: A secondary analysis

IntroductionDespite the well-known linkages between poor emotion regulation and subjective smoking motives, little is known about the role of emotion regulation in predicting smoking reinforcement behavior. This study examined the relation between difficulties in emotion regulation and puff velocity data, a behavioral index of smoking reinforcement, in adult daily cigarette smokers. MethodThe current study was a secondary analysis of data collected from non-treatment seeking daily smokers (N = 124). Participants completed the Difficulties in Emotion Regulation Scale (DERS) followed by an ad libitum smoking period during which puff topography data was collected via a handheld puffing device. Puff velocity served as our puff topography index and was examined at the average and puff-to-puff level using regression and multi-level models, respectively. ResultsRegression analyses showed no significant association between DERS scores and average puff velocity. In contrast, multi-level modeling found a significant quadratic time × DERS effect at the puff-to-puff level, such that those with greater emotion regulation difficulties inhaled more quickly at the initiation of the cigarette, whereas those with lower emotion regulation difficulties evidenced consistent puffing over the course of the cigarette. DiscussionSmokers with greater difficulties in emotion regulation appear to smoke in a way that maximizes delivery of nicotine, perhaps to self-regulate distress. One’s style of puffing may reflect a possible behavioral marker of negative reinforcement smoking, especially in the context of emotional distress. ImplicationsThis study was the first to explore the relationship between difficulties in emotion regulation and a behavioral measure of smoking reinforcement.

Association between woodsmoke and respiratory health: A Dutch panel study

Background and aim: In the Netherlands household fireplaces are responsible for burning about 1 billion kilograms of wood per year, emitting a significant amount of woodsmoke. Little is known about the respiratory health effects associated with the level of woodsmoke exposure present in the Netherlands. Thus, our aim was to investigate the short-term changes in lung function, respiratory symptoms and medication use associated with short-term changes in woodsmoke exposures in citizens with and without COPD/asthma. The study was co-created with citizens. Methods: We conducted a panel study with repeated observations in 46 adults (11 asthma/COPD) between February and May 2021 in four Dutch cities. Participants were asked to document symptoms and medication use in a daily diary and conduct daily home spirometry measurements in the morning and evening. Woodsmoke exposure was characterized by measuring various exposures at central sites in each study location set-up specifically for the study, and individual woodsmoke perception (smell) recorded in the daily diaries. The association between woodsmoke and health was analyzed using linear and logistic regression, adjusting for time-varying confounders and repeated observations. Results: We found significant positive associations between the specific wood smoke marker levoglucosan and shortness of breath during rest (OR 1.15 (95%CI 1.01, 1.32) per IQR increment for previous day exposure) and extra medication use (OR 1.19 (95%CI 1.07, 1.33) per IQR increment for current day exposure). We found weak associations between woodsmoke and nasal symptoms, and no consistent association with either morning or evening lung function measurements. The associations with levoglucosan remained after the inclusion of generic PM2.5 as a co-pollutant in the statistical models. Conclusion: People experienced more shortness of breath at rest, nasal symptoms and used more medication on days with higher levels of outdoor woodsmoke exposure. Keywords: Woodsmoke, Levoglucosan, Respiratory health, Panel study.

Biological Assessment of Potential Exposure to Occupational Substances in Current Semiconductor Workers with at Least 5 Years of Employment.

Background: this study aimed to conduct a biological assessment of the potential exposure to carcinogenic substances in current semiconductor workers. Methods: A cross-sectional study was conducted on 306 semiconductor workers. The assessed biomarkers were as follows: (benzene) urine S-phenylmercapturic, trans,trans-muconic acid, blood benzene; (trichloroethylene) urine trichloroacetic acid; (2-ethoxyethanol) 2-ethoxyacetic acid; (arsine) urine arsenic3+, arsenic5+, monomethylarsonic, dimethylarsinic acid, arsenobetaine; (shift work) 6-hydroxymelatonin; (smoking) cotinine, and (radiation). The detection rate of these materials is defined as more than the biological exposure index (BEI) or the previous reference value. Results: Some workers exposed to trans,trans-muconic acid, trichloroacetic acid, and arsenic5+ showed high BEI levels. Generally, there was no difference according to job categories, and workers were suspected to be exposed to other sources. The melatonin concentration tended to decrease when working at night, and cotinine was identified as an excellent surrogate marker for smoking. In the case of radiation exposure, there was no significant difference in the number of stable chromosome translocation in 19 semiconductor workers. Their estimated radiation exposure level was below the limit of detection (LOD) or near the LOD level. Conclusion: In this study, most carcinogens were below the BEI level, but verification through re-measurement was needed for workers who were identified to have a high BEI level. For continuous monitoring, a prospective cohort is necessary to deal with the healthy worker effect and assess additional materials.

Maternal Urinary Cotinine Concentrations During Pregnancy Predict Infant BMI Trajectory After Birth: Analysis of 89617 Mother-Infant Pairs in the Japan Environment and Children's Study.

BackgroundClinical or epidemiological conclusions remain undecided on the direct effects of active and second-hand smoking during pregnancy on childhood obesity. Urinary cotinine (UC) concentration, an accurate and quantitative marker for smoking, may elucidate the dose-dependent relationship between smoking during pregnancy and childhood obesity. To analyze the relationship between UC concentration and smoking questionnaire (SQ) classes for active and second-hand smoking in pregnant mothers and trajectory of infant Kaup index (body mass index: BMI).MethodsThis multicenter prospective cohort study was conducted using a list-wise complete set of 35829 among 89617 mother-infant singleton pairs, recruited between 2011 and 2014, in the Japan Environment and Children’s Study (JECS). Pairs were categorized according to UC levels (1 to 4 classes) or SQ (0 to 4 classes).ResultsMaternal BMI at delivery was the highest in UC class 4 (highest). Maternal and paternal education of ≥16 years and annual household income were lowest in UC class 4. Infant BMI was lower at birth, but trends in BMI and ΔBMI were higher from six to 36 months step-wise in the UC classes. The above tendency was observed in the list-wise complete dataset but was emphasized after multiple imputations and corrections of cofounders. UC concentration in five SQ classes largely fluctuated, and the relationship between SQ classes and trends in BMI and ΔBMI was not statistically significant.ConclusionInfants from high UC mothers had a low BMI at birth, increasing from six to 36 months of age. UC concentrations, but not smoking questionnaire classes, predict infant BMI trajectory, suggesting that active and second-hand smoking affect child obesity in a dose-dependent manner.

Concentration of smoke marker compounds in non‐smoke‐exposed grapes and wine in Australia

Background and Aims An elevated concentration of several volatile phenols and their glycosides in grapes and wines is associated with exposure of grapes to forest fire smoke. Interpretation of phenol compositional data from grapes or wines, however, is complicated by the fact that traces of these compounds can be detected in non-smoke-exposed samples. Hence, the concentration of smoke marker compounds was investigated with the aim of providing a reference data set to help determine smoke exposure. Methods and Results Thirteen phenolic compounds were measured in non-smoke-exposed grape berries and unoaked wines made from 12 cultivars collected from multiple regions across Australia over four vintages. The grapes and wines contained a low concentration of several volatile phenols and their glycosides. These varied in concentration between cultivars but showed little variation between regions and vintages. The maximum concentration observed for any analyte was below 15 μg/kg in grapes and approximately 15 μg/L in wine. Conclusions The results for smoke marker compounds should be considered on a per-cultivar basis when determining smoke exposure. Interpretation of results for a potentially smoke-exposed sample can be achieved based on comparison with the 99th percentile values reported here. Use of the interpretation system described should be limited to determining smoke exposure and not smoke taint. Significance of the Study This study provides a comprehensive set of data that defines the upper limits of smoke marker compounds expected in Australian grapes and wines from non-smoke-exposed vineyards that can be used for determining the likelihood of smoke exposure.

Microsatellite instability is biased in Amsterdam II-defined Lynch-related cancer cases with family history but is rare in other cancers: a summary of 1000 analyses

BackgroundMicrosatellite instability (MSI) is a key marker for predicting the response of immune checkpoint inhibitors (ICIs) and for screening Lynch syndrome (LS).AimThis study aimed to see the characteristics of cancers with high level of MSI (MSI-H) in genetic medicine and precision medicine.MethodsThis study analyzed the incidence of MSI-H in 1000 cancers and compared according to several clinical and demographic factors.ResultsThe incidence of MSI-H was highest in endometrial cancers (26.7%, 20/75), followed by small intestine (20%, 3/15) and colorectal cancers (CRCs)(13.7%, 64/466); the sum of these three cancers (15.6%) was significantly higher than that of other types (2.5%)(P < 0.0001). MSI-H was associated with LS-related cancers (P < 0.0001), younger age (P = 0.009), and family history, but not with smoking, drinking, or serum hepatitis virus markers. In CRC cases, MSI-H was significantly associated with a family history of LS-related cancer (P < 0.0001), Amsterdam II criteria [odds ratio (OR): 5.96], right side CRCs (OR: 4.89), and multiplicity (OR: 3.31). However, MSI-H was very rare in pancreatic (0.6%, 1/162) and biliary cancers (1.6%, 1/64) and was null in 25 familial pancreatic cancers. MSI-H was more recognized in cancers analyzed for genetic counseling (33.3%) than in those for ICI companion diagnostics (3.1%)(P < 0.0001). Even in CRCs, MSI-H was limited to 3.3% when analyzed for drug use.ConclusionsMSI-H was predominantly recognized in LS-related cancer cases with specific family histories and younger age. MSI-H was limited to a small proportion in precision medicine especially for non-LS-related cancer cases.

Primary aromatic amines in indoor dust from 10 countries and associated human exposure

Although primary aromatic amines (AAs) are widely used in consumer products, little is known about their occurrence in indoor dust. A liquid chromatography - tandem mass spectrometry (LC-MS/MS) method was applied for the determination of 29 AAs and two tobacco smoke markers (nicotine and cotinine) in 256 house dust samples collected from 10 countries. Of the 29 AAs analyzed, p-anisidine, o-anisidine, 2,6-dimethylaniline (2,6-DMA), p-cresidine (p-CD), p-toluidine (p-TD), 4,4'-methylenedianiline (4,4'-MDA), ortho/meta-toluidine (o/m-TD), 4-chloroaniline (4-CA), 2,4-diaminotoluene (2,4-DAT), aniline, and 2-naphthylamine (2-NA) as well as nicotine and cotinine, were found prevalent in house dust samples. Sum median concentrations of AAs and tobacco smoke markers varied from 29.6 to 576ng/g (overall median: 200ng/g) and 10.8 to 2920ng/g (415ng/g), respectively. Among AAs, aniline was the abundant contaminant, found at median concentrations ranging from 19.6ng/g (Colombia) to 334ng/g (South Korea). Nicotine was detected in all indoor samples at median concentrations ranging from 9.92ng/g (Colombia) to 2790ng/g (India) ng/g. Concentrations of AAs in indoor dust were significantly correlated with those of nicotine. Estimated daily intake (EDI) of select AAs through the ingestion of house dust was in the range of 0.019-3.03ng/kg-bw/day, which was five orders of magnitude below the tolerance limits.