Randomised controlled trial of real-time feedback and brief coaching to reduce indoor smoking.

BACKGROUND: Previous secondhand smoke (SHS) reduction interventions have provided only delayed feedback on reported smoking behaviour, such as coaching, or presenting results from child cotinine assays or air particle counters. DESIGN: This SHS reduction trial assigned families at random to brief coaching and continuous real-time feedback (intervention) or measurement-only (control) groups. PARTICIPANTS: We enrolled 298 families with a resident tobacco smoker and a child under age 14. INTERVENTION: We installed air particle monitors in all homes. For the intervention homes, immediate light and sound feedback was contingent on elevated indoor particle levels, and up to four coaching sessions used prompts and praise contingent on smoking outdoors. Mean intervention duration was 64 days. MEASURES: The primary outcome was 'particle events' (PEs) which were patterns of air particle concentrations indicative of the occurrence of particle-generating behaviours such as smoking cigarettes or burning candles. Other measures included indoor air nicotine concentrations and participant reports of particle-generating behaviour. RESULTS: PEs were significantly correlated with air nicotine levels (r=0.60) and reported indoor cigarette smoking (r=0.51). Interrupted time-series analyses showed an immediate intervention effect, with reduced PEs the day following intervention initiation. The trajectory of daily PEs over the intervention period declined significantly faster in intervention homes than in control homes. Pretest to post-test, air nicotine levels, cigarette smoking and e-cigarette use decreased more in intervention homes than in control homes. CONCLUSIONS: Results suggest that real-time particle feedback and coaching contingencies reduced PEs generated by cigarette smoking and other sources. TRIAL REGISTRATION NUMBER: NCT01634334; Post-results.

Acrolein Exposure in Hookah Smokers and Non-Smokers Exposed to Hookah Tobacco Secondhand Smoke: Implications for Regulating Hookah Tobacco Products.

Introduction: Acrolein is a highly ciliatoxic agent, a toxic respiratory irritant, a cardiotoxicant, and a possible carcinogen present in tobacco smoke including hookah tobacco. Methods: 105 hookah smokers and 103 non-smokers attended exclusively hookah smoking social events at either a hookah lounge or private home, and provided urine samples the morning of and the morning after the event. Samples were analyzed for 3-hydroxypropylmercapturic acid (3-HPMA), a metabolite of acrolein. Results: Geometric mean (GM) urinary 3-HPMA levels in hookah smokers and non-smokers exposed to secondhand smoke (SHS) increased significantly, 1.41 times, 95% CI = 1.15 to 1.74 and 1.39 times, 95% CI = 1.16 to 1.67, respectively, following a hookah social event. The highest increase (1.68 times, 95% CI = 1.15 to 2.45; p = 0.007) in 3-HPMA post a hookah social event was among daily hookah smokers (GM, from 1991 pmol/mg to 3348 pmol/mg). Pre-to-post event change in urinary 3-HPMA was significantly positively correlated with pre-to-post event change in urinary cotinine among hookah smokers at either location of hookah event, (ρ = 0.359, p = 0.001), and among non-smokers in hookah lounges (ρ = 0.369, p = 0.012). Conclusions: Hookah tobacco smoke is a source of acrolein exposure. Findings support regulating hookah tobacco products including reducing humectants and sugar additives, which are precursors of acrolein under certain pyrolysis conditions. We suggest posting health warning signs for indoor smoking in hookah lounges, and encouraging voluntary bans of smoking hookah tobacco in private homes. Implications: Our study is the first to quantify the increase in acrolein exposure in hookah smokers and non-smokers exposed to exclusively hookah tobacco SHS at hookah social events in homes or hookah lounges. Our findings provide additional support for regulating hookah tobacco product content, protecting non-smokers' health by posting health warning signs for indoor smoking in hookah lounges, and encouraging home bans on hookah tobacco smoking to safeguard vulnerable residents.

Urinary NNAL in hookah smokers and non-smokers after attending a hookah social event in a hookah lounge or a private home.

Tobacco smoking and exposure to tobacco secondhand smoke (SHS) can cause lung cancer. We determined uptake of NNK (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone), a tobacco specific potent pulmonary carcinogen, in hookah smokers and non-smokers exposed to hookah tobacco SHS. We analyzed data from a community-based convenience sample of 201 of adult (aged ≥18 years) exclusive hookah smokers (n = 99) and non-smokers (n = 102) residing in San Diego County, California. Participants spent an average of three consecutive hours indoors, in hookah lounges or private homes, where hookah tobacco was smoked exclusively. Total NNAL [the sum of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides], the major metabolites of NNK, were quantified in spot urine samples provided the morning of and the morning after attending a hookah event. Among hookah smokers urinary NNAL increased significantly (p<0.001) following a hookah social event; the geometric mean doubled, from 1.97 to 4.16 pg/mg. Among non-smokers the increase was not significant (p = 0.059). Post hookah event urinary NNAL levels were highest in daily hookah smokers, and significantly higher than in non-daily smokers or non-smokers (GM: 14.96 pg/mg vs. 3.13 pg/mg and 0.67 pg/mg, respectively). For both hookah smokers and non-smokers, pre-to-post event change in urinary NNAL was not significantly different between hookah lounges and homes. We suggest posting health warning signs inside hookah lounges, and encouraging voluntary bans of smoking hookah tobacco in private homes.

When smokers quit: exposure to nicotine and carcinogens persists from thirdhand smoke pollution.

BACKGROUND: Over a 6-month period, we examined tobacco smoke pollutants (also known as thirdhand smoke, THS) that remained in the homes of former smokers and the exposure to these pollutants. METHODS: 90 smokers completed study measures at baseline (BL). Measures were repeated among verified quitters 1 week (W1), 1 month (M1), 3 months (M3) and 6 months (M6) following cessation. Measures were analysed for THS pollutants on household surfaces, fingers and in dust (ie, nicotine, tobacco-specific nitrosamines) and for urinary markers of exposure (ie, cotinine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)). RESULTS: We observed significant short-term reduction of nicotine on surfaces (BL: 22.2 µg/m2, W1: 10.8 µg/m2) and on fingers of non-smoking residents (BL: 29.1 ng/wipe, W1: 9.1 ng/wipe) without further significant changes. Concentrations of nicotine and nicotine-derived nitrosamine ketone (NNK) in dust did not change and remained near BL levels after cessation. Dust nicotine and NNK loadings significantly increased immediately following cessation (nicotine BL: 5.0 µg/m2, W1: 9.3 µg/m2; NNK BL: 11.6 ng/m2, W1: 36.3 ng/m2) before returning to and remaining at near BL levels. Cotinine and NNAL showed significant initial declines (cotinine BL: 4.6 ng/mL, W1: 1.3 ng/mL; NNAL BL: 10.0 pg/mL, W1: 4.2 pg/mL) without further significant changes. CONCLUSIONS: Homes of smokers remained polluted with THS for up to 6 months after cessation. Residents continued to be exposed to THS toxicants that accumulated in settled house dust and on surfaces before smoking cessation. Further research is needed to better understand the consequences of continued THS exposure after cessation and the efforts necessary to remove THS.

Identification of sphingolipid metabolites that induce obesity via misregulation of appetite, caloric intake and fat storage in Drosophila.

Obesity is defined by excessive lipid accumulation. However, the active mechanistic roles that lipids play in its progression are not understood. Accumulation of ceramide, the metabolic hub of sphingolipid metabolism, has been associated with metabolic syndrome and obesity in humans and model systems. Here, we use Drosophila genetic manipulations to cause accumulation or depletion of ceramide and sphingosine-1-phosphate (S1P) intermediates. Sphingolipidomic profiles were characterized across mutants for various sphingolipid metabolic genes using liquid chromatography electrospray ionization tandem mass spectroscopy. Biochemical assays and microscopy were used to assess classic hallmarks of obesity including elevated fat stores, increased body weight, resistance to starvation induced death, increased adiposity, and fat cell hypertrophy. Multiple behavioral assays were used to assess appetite, caloric intake, meal size and meal frequency. Additionally, we utilized DNA microarrays to profile differential gene expression between these flies, which mapped to changes in lipid metabolic pathways. Our results show that accumulation of ceramides is sufficient to induce obesity phenotypes by two distinct mechanisms: 1) Dihydroceramide (C14:0) and ceramide diene (C14:2) accumulation lowered fat store mobilization by reducing adipokinetic hormone- producing cell functionality and 2) Modulating the S1P: ceramide (C14:1) ratio suppressed postprandial satiety via the hindgut-specific neuropeptide like receptor dNepYr, resulting in caloric intake-dependent obesity.

Children's exposure to secondhand and thirdhand smoke carcinogens and toxicants in homes of hookah smokers.

INTRODUCTION: We examined homes of hookah-only smokers and nonsmokers for levels of indoor air nicotine (a marker of secondhand smoke) and indoor surface nicotine (a marker of thirdhand smoke), child uptake of nicotine, the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and the toxicant acrolein by analyzing their corresponding metabolites cotinine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and NNAL-glucuronides (total NNAL) and 3-hydroxypropylmercapturic acid. METHODS: Data were collected at 3 home visits during a 7-day study period from a convenience sample of 24 households with a child 5 years or younger. Three child urine samples and 2 air and surface samples from the living room and the child bedroom were taken in homes of nonsmokers (n = 5) and hookah-only smokers (n = 19) comprised of daily hookah smokers (n = 8) and weekly/monthly hookah smokers (n = 11). RESULTS: Nicotine levels in indoor air and on surfaces in the child bedrooms in homes of daily hookah smokers were significantly higher than in homes of nonsmokers. Uptake of nicotine, NNK, and acrolein in children living in daily hookah smoker homes was significantly higher than in children living in nonsmoker homes. Uptake of nicotine and NNK in children living in weekly/monthly hookah smoker homes was significantly higher than in children living in nonsmoker homes. CONCLUSIONS: Our data provide the first evidence for uptake of nicotine, the tobacco-specific lung carcinogen NNK, and the ciliatoxic and cardiotoxic agent acrolein in children living in homes of hookah smokers. Our findings suggest that daily and occasional hookah use in homes present a serious, emerging threat to children's long-term health.

Thirdhand smoke and exposure in California hotels: non-smoking rooms fail to protect non-smoking hotel guests from tobacco smoke exposure.

INTRODUCTION: This study examined tobacco smoke pollution (also known as thirdhand smoke, THS) in hotels with and without complete smoking bans and investigated whether non-smoking guests staying overnight in these hotels were exposed to tobacco smoke pollutants. METHODS: A stratified random sample of hotels with (n=10) and without (n=30) complete smoking bans was examined. Surfaces and air were analysed for tobacco smoke pollutants (ie, nicotine and 3-ethynylpyridine, 3EP). Non-smoking confederates who stayed overnight in guestrooms provided urine and finger wipe samples to determine exposure to nicotine and the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone as measured by their metabolites cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), respectively. FINDINGS: Compared with hotels with complete smoking bans, surface nicotine and air 3EP were elevated in non-smoking and smoking rooms of hotels that allowed smoking. Air nicotine levels in smoking rooms were significantly higher than those in non-smoking rooms of hotels with and without complete smoking bans. Hallway surfaces outside of smoking rooms also showed higher levels of nicotine than those outside of non-smoking rooms. Non-smoking confederates staying in hotels without complete smoking bans showed higher levels of finger nicotine and urine cotinine than those staying in hotels with complete smoking bans. Confederates showed significant elevations in urinary NNAL after staying in the 10 most polluted rooms. CONCLUSIONS: Partial smoking bans in hotels do not protect non-smoking guests from exposure to tobacco smoke and tobacco-specific carcinogens. Non-smokers are advised to stay in hotels with complete smoking bans. Existing policies exempting hotels from complete smoking bans are ineffective.

Wipe sampling for nicotine as a marker of thirdhand tobacco smoke contamination on surfaces in homes, cars, and hotels.

INTRODUCTION: Secondhand smoke contains a mixture of pollutants that can persist in air, dust, and on surfaces for months or longer. This persistent residue is known as thirdhand smoke (THS). Here, we detail a simple method of wipe sampling for nicotine as a marker of accumulated THS on surfaces. METHODS: We analyzed findings from 5 real-world studies to investigate the performance of wipe sampling for nicotine on surfaces in homes, cars, and hotels in relation to smoking behavior and smoking restrictions. RESULTS: The intraclass correlation coefficient for side-by-side samples was 0.91 (95% CI: 0.87-0.94). Wipe sampling for nicotine reliably distinguished between private homes, private cars, rental cars, and hotels with and without smoking bans and was significantly positively correlated with other measures of tobacco smoke contamination such as air and dust nicotine. The sensitivity and specificity of possible threshold values (0.1, 1, and 10 µg/m(2)) were evaluated for distinguishing between nonsmoking and smoking environments. Sensitivity was highest at a threshold of 0.1 µg/m(2), with 74%-100% of smoker environments showing nicotine levels above threshold. Specificity was highest at a threshold of 10 µg/m(2), with 81%-100% of nonsmoker environments showing nicotine levels below threshold. The optimal threshold will depend on the desired balance of sensitivity and specificity and on the types of smoking and nonsmoking environments. CONCLUSIONS: Surface wipe sampling for nicotine is a reliable, valid, and relatively simple collection method to quantify THS contamination on surfaces across a wide range of field settings and to distinguish between nonsmoking and smoking environments.

Towards smoke-free rental cars: an evaluation of voluntary smoking restrictions in California.

INTRODUCTION: Some car rental companies in California and other states in the USA have established non-smoking policies for their vehicles. This study examined the effectiveness of these policies in maintaining smoke-free rental cars. METHODS: A stratified random sample of 250 cars (non-smoker, smoker and unknown designation) was examined in San Diego County, California, USA. Dust, surfaces and the air of each vehicle cabin were sampled and analysed for residual tobacco smoke pollutants (also known as thirdhand smoke (THS)), and each car was inspected for visual and olfactory signs of tobacco use. Customer service representatives were informally interviewed about smoking policies. FINDINGS: A majority of putative non-smoker cars had nicotine in dust, on surfaces, in air and other signs of tobacco use. Independent of a car's smoking status, older and higher mileage cars had higher levels of THS pollution in dust and on surfaces (p<0.05), indicating that pollutants accumulated over time. Compared with smoker cars, non-smoker cars had lower levels of nicotine on surfaces (p<0.01) and in dust (p<0.05) and lower levels of nicotine (p<0.05) and 3-ethynylpyridine (p<0.05) in the air. Non-smoking signage in cars was associated with lower levels of THS pollutants in dust and air (p<0.05). CONCLUSIONS: Existing policies and practices were successful in lowering THS pollution levels in non-smoker cars compared with smoker cars. However, policies failed in providing smoke-free rental cars; THS levels were not as low as those found in private cars of non-smokers with in-car smoking bans. Major obstacles include inconsistent communication with customers and the lack of routine monitoring and enforcement strategies. Strengthening policies and their implementation would allow car rental companies to reduce costs, better serve their customers and make a constructive contribution to tobacco control efforts.

Environmental tobacco smoke as a source of polycyclic aromatic hydrocarbons in settled household dust.

Environmental tobacco smoke is a major contributor to indoor air pollution. Dust and surfaces may remain contaminated long after active smoking has ceased (called 'thirdhand' smoke). Polycyclic aromatic hydrocarbons (PAHs) are known carcinogenic components of tobacco smoke found in settled house dust (SHD). We investigated whether tobacco smoke is a source of PAHs in SHD. House dust was collected from 132 homes in urban areas of Southern California. Total PAHs were significantly higher in smoker homes than nonsmoker homes (by concentration: 990 ng/g vs 756 ng/g, p = 0.025; by loading: 1650 ng/m(2) vs 796 ng/m(2), p = 0.012). We also found significant linear correlations between nicotine and total PAH levels in SHD (concentration, R(2) = 0.105; loading, R(2) = 0.385). Dust collected per square meter (g/m(2)) was significantly greater in smoker homes and might dilute PAH concentration in SHD inconsistently. Therefore, dust PAH loading (ng PAH/m(2)) is a better indicator of PAH content in SHD. House dust PAH loadings in the bedroom and living room in the same home were significantly correlated (R(2) = 0.468, p < 0.001) suggesting PAHs are distributed by tobacco smoke throughout a home. In conclusion, tobacco smoke is a source of PAHs in SHD, and tobacco smoke generated PAHs are a component of thirdhand smoke.

When smokers move out and non-smokers move in: residential thirdhand smoke pollution and exposure.

BACKGROUND: This study examined whether thirdhand smoke (THS) persists in smokers' homes after they move out and non-smokers move in, and whether new non-smoking residents are exposed to THS in these homes. METHODS: The homes of 100 smokers and 50 non-smokers were visited before the residents moved out. Dust, surfaces, air and participants' fingers were measured for nicotine and children's urine samples were analysed for cotinine. The new residents who moved into these homes were recruited if they were non-smokers. Dust, surfaces, air and new residents' fingers were examined for nicotine in 25 former smoker and 16 former non-smoker homes. A urine sample was collected from the youngest resident. RESULTS: Smoker homes' dust, surface and air nicotine levels decreased after the change of occupancy (p<0.001); however dust and surfaces showed higher contamination levels in former smoker homes than former non-smoker homes (p<0.05). Non-smoking participants' finger nicotine was higher in former smoker homes compared to former non-smoker homes (p<0.05). Finger nicotine levels among non-smokers living in former smoker homes were significantly correlated with dust and surface nicotine and urine cotinine. CONCLUSIONS: These findings indicate that THS accumulates in smokers' homes and persists when smokers move out even after homes remain vacant for 2 months and are cleaned and prepared for new residents. When non-smokers move into homes formerly occupied by smokers, they encounter indoor environments with THS polluted surfaces and dust. Results suggest that non-smokers living in former smoker homes are exposed to THS in dust and on surfaces.

Residual tobacco smoke in used cars: futile efforts and persistent pollutants.

INTRODUCTION: Smoking cigarettes in the enclosed environment of a car leads to the contamination of a car's microenvironment with residual tobacco smoke pollution (TSP). METHODS: Surface wipe, air, and dust samples were collected in used cars sold by nonsmokers (n = 40) and smokers (n = 87) and analyzed for nicotine. Primary drivers were interviewed about smoking behavior and restrictions, and car interiors were inspected to investigate (a) differences in car dustiness, signs of past smoking, ventilation use, mileage, and passenger cabin volume among nonsmokers and smokers with and without in-car smoking bans and (b) factors that contribute to the contamination of cars with residual TSP, such as ventilation use, cleaning behaviors, signs of past smoking, and holding the cigarette near/outside the car window while smoking. RESULTS: Smokers reported using air conditioning less (p < .05) and driving with windows down more often than nonsmokers (p = .05); their cars were also dustier (p < .01) and exhibited more ash and burn marks than nonsmokers' cars (p < .001). Number of cigarettes smoked by the primary driver was the strongest predictor of residual TSP indicators (R(2) = .10 - .16, p = .001). This relationship was neither mediated by ash or burn marks nor moderated by efforts to remove residual TSP from the vehicle (i.e., cleaning, ventilation) or attempts to prevent tobacco smoke pollutants from adsorbing while smoking (e.g., holding the cigarette near/outside window). DISCUSSION: Findings suggest that smokers can prevent their cars from becoming contaminated with residual TSP by reducing or ceasing smoking; however, commonly used cleaning and ventilation methods did not successfully decrease contamination levels. Disclosure requirements and smoke-free certifications could help protect buyers of used cars and empower them to request nonsmoking environments or a discount on cars that have been smoked in previously.

Systemic and heart autonomous effects of sphingosine Δ4 desaturase deficiency in lipotoxic cardiac pathophysiology.

Lipotoxic cardiomyopathy (LCM) is characterized by cardiac steatosis, including the accumulation of fatty acids, triglycerides and ceramides. Model systems have shown the inhibition of ceramide biosynthesis to antagonize obesity and improve insulin sensitivity. Sphingosine Δ4 desaturase (encoded by ifc in Drosophila melanogaster) enzymatically converts dihydroceramide into ceramide. Here, we examine ifc mutants to study the effects of desaturase deficiency on cardiac function in Drosophila Interestingly, ifc mutants exhibited classic hallmarks of LCM: cardiac chamber dilation, contractile defects and loss of fractional shortening. This outcome was phenocopied in global ifc RNAi-mediated knockdown flies. Surprisingly, cardiac-specific ifc knockdown flies exhibited cardiac chamber restriction with no contractile defects, suggesting heart autonomous and systemic roles for ifc activity in cardiac function. Next, we demonstrated that ifc mutants exhibit suppressed Sphingosine kinase 1 (Sk1) expression. Ectopic overexpression of Sk1 was sufficient to prevent cardiac chamber dilation and loss of fractional shortening in ifc mutants. Partial rescue was also observed with cardiac- and fat-body-specific Sk1 overexpression. Finally, we showed that cardiac-specific expression of Drosophila inhibitor of apoptosis (dIAP) also prevented cardiac dysfunction in ifc mutants, suggesting a role for caspase activity in the observed cardiac pathology. Collectively, we show that spatial regulation of sphingosine Δ4 desaturase activity differentially affects cardiac function in heart autonomous and systemic mechanisms through tissue interplay.

Acetylcholine Regulates Pulmonary Pathology During Viral Infection and Recovery.

INTRODUCTION: This study was designed to explore the role of acetylcholine (ACh) in pulmonary viral infection and recovery. Inflammatory control is critical to recovery from respiratory viral infection. ACh secreted from non-neuronal sources, including lymphocytes, plays an important, albeit underappreciated, role in regulating immune-mediated inflammation. METHODS: ACh and lymphocyte cholinergic status in the lungs were measured over the course of influenza infection and recovery. The role of ACh was examined by inhibiting ACh synthesis in vivo. Pulmonary inflammation was monitored by Iba1 immunofluorescence, using a novel automated algorithm. Tissue repair was monitored histologically. RESULTS: Pulmonary ACh remained constant through the early stage of infection and increased during the peak of the acquired immune response. As the concentration of ACh increased, cholinergic lymphocytes appeared in the BAL and lungs. Cholinergic capacity was found primarily in CD4 T cells, but also in B cells and CD8 T cells. The cholinergic CD4+ T cells bound to influenza-specific tetramers and were retained in the resident memory regions of the lung up to 2 months after infection. Histologically, cholinergic lymphocytes were found in direct physical contact with activated macrophages throughout the lung. Inflammation was monitored by ionized calcium-binding adapter molecule 1 (Iba1) immunofluorescence, using a novel automated algorithm. When ACh production was inhibited, mice exhibited increased tissue inflammation and delayed recovery. Histologic examination revealed abnormal tissue repair when ACh was limited. CONCLUSION: These findings point to a previously unrecognized role for ACh in the transition from active immunity to recovery and pulmonary repair following respiratory viral infection.

Altered bile acid metabolism in childhood functional constipation: inactivation of secretory bile acids by sulfation in a subset of patients.

OBJECTIVE: An elevated concentration in the colon of the primary bile acid chenodeoxycholic acid (CDCA) or the secondary bile acid deoxycholic acid (DCA) is known to induce water secretion, causing diarrhea. We hypothesized that of the many fecal bile acids, only CDCA and DCA function as endogenous laxatives; therefore, a decrease in their proportion may be a cause of childhood functional constipation. To test this possibility, fecal bile acid composition was determined in children with functional constipation and in nonconstipated control children. PATIENTS AND METHODS: Fecal samples were obtained from 207 children, 103 with functional constipation and 104 with normal bowel habits. Bile acid classes were determined by use of electrospray ionization-single ion monitoring-mass spectrometry (ESI-SIM-MS), and individual bile acids were measured by gas chromatography (GC)-MS (GC-MS). The structure of individual sulfated bile acids was obtained by use of liquid chromatography (LC)-MS (LC-MS). RESULTS: By ESI-SIM-MS, the proportions of DCA did not differ in constipated children (n = 73) from that in control children (n = 92), but monosulfated dihydroxy bile acids were greater (P < 0.05). The difference was attributable to 6 patients in the constipated group whose major fecal bile acid by LC-MS was the 3-sulfate of CDCA. Sulfation of CDCA is known to abolish its secretory activity. By GC-MS, the bile acid profile was identical in the 2 groups. CONCLUSIONS: In most children with functional constipation, the fecal bile acid profile seems to be normal. There is a small subset of children, however, whose dominant fecal bile acid is the 3-sulfate of CDCA, indicating a novel disturbance in bile acid metabolism. Such sulfation abolishes the secretory activity of CDCA and may contribute to constipation.

Ceramide-Protein Interactions Modulate Ceramide-Associated Lipotoxic Cardiomyopathy.

Lipotoxic cardiomyopathy (LCM) is characterized by abnormal myocardial accumulation of lipids, including ceramide; however, the contribution of ceramide to the etiology of LCM is unclear. Here, we investigated the association of ceramide metabolism and ceramide-interacting proteins (CIPs) in LCM in the Drosophila heart model. We find that ceramide feeding or ceramide-elevating genetic manipulations are strongly associated with cardiac dilation and defects in contractility. High ceramide-associated LCM is prevented by inhibiting ceramide synthesis, establishing a robust model of direct ceramide-associated LCM, corroborating previous indirect evidence in mammals. We identified several CIPs from mouse heart and Drosophila extracts, including caspase activator Annexin-X, myosin chaperone Unc-45, and lipogenic enzyme FASN1, and remarkably, their cardiac-specific manipulation can prevent LCM. Collectively, these data suggest that high ceramide-associated lipotoxicity is mediated, in part, through altering caspase activation, sarcomeric maintenance, and lipogenesis, thus providing evidence for conserved mechanisms in LCM pathogenesis in mammals.

Levels of Urine Cotinine from Hookah Smoking and Exposure to Hookah Tobacco Secondhand Smoke in Hookah Lounges and Homes.

BACKGROUND: Nicotine, an addictive drug, is present in all forms of tobacco products, including hookah tobacco, which is not yet regulated in the United States. OBJECTIVES: This study aimed to investigate the uptake of nicotine in hookah smokers and non-smokers exposed to secondhand smoke (SHS) at indoor hookah social events in natural settings where hookah tobacco was smoked exclusively. PATIENTS AND METHODS: We quantified cotinine, a metabolite of nicotine, in the urine of 105 hookah smokers and 103 non-smokers. Participants provided spot urine samples the morning of and the morning after attending an indoor hookah-only smoking social event at a hookah lounge or in a private home. RESULTS: Following a social event where exclusively hookah tobacco was smoked, urinary cotinine levels increased significantly 8.5 times (geometric mean (GM): 16.0 ng/mg to 136.1 ng/mg) among hookah smokers, and 2.5 times (GM: 0.4 ng/mg to 1.0 ng/mg) among non-smokers exposed exclusively to hookah tobacco SHS. Among hookah smokers, the highest increase in urinary cotinine levels post a hookah event was found in occasional hookah smokers in which GM levels increased significantly 31.2 times post smoking (from 2.0 ng/mg to 62.3 ng/mg). Reported reasons for preference to smoke hookah at home by hookah smokers who attended a hookah social event in a private home included recreational purposes, socializing with friends and family, 'Me' time and relaxing at home, more comfortable to smoke hookah at home, owning a hookah and hookah tobacco, eating and drinking while smoking hookah, and saving money by smoking at home and not going to hookah lounges. CONCLUSIONS: Hookah tobacco smoke is a source of substantial nicotine exposure. Our results call for protecting hookah smokers' and non-smokers' health by requiring accurate hookah tobacco labels, raising taxes on hookah tobacco, reducing the spread of hookah lounges, and encouraging voluntary bans on smoking hookah tobacco in private homes.

Benzene uptake in Hookah smokers and non-smokers attending Hookah social events: regulatory implications.

BACKGROUND: Benzene is a human hematotoxicant and a leukemogen that causes lymphohematopoietic cancers, especially acute myelogenous leukemia. We investigated uptake of benzene in hookah smokers and non-smokers attending hookah social events in naturalistic settings where hookah tobacco was smoked exclusively. METHODS: We quantified S-phenylmercapturic acid (SPMA), a metabolite of benzene, in the urine of 105 hookah smokers and 103 non-smokers. Participants provided spot urine samples the morning of and the morning after attending an indoor hookah-only smoking social event at a hookah lounge or in a private home. RESULTS: Urinary SPMA levels in hookah smokers increased significantly following a hookah social event (P < 0.001). This increase was 4.2 times higher after hookah lounge events (P < 0.001) and 1.9 times higher after home events (P = 0.003). In non-smokers, urinary SPMA levels increased 2.6 times after hookah lounge events (P = 0.055); however, similar urinary SPMA levels were detected before and after home events, possibly indicating chronic exposure to benzene (P = 0.933). CONCLUSIONS: Our data provide the first evidence for uptake of benzene in hookah smokers and non-smokers exposed to hookah tobacco secondhand smoke at social events in private homes compared with their counterparts in hookah lounges. Hookah tobacco smoke is a source of benzene exposure, a risk factor for leukemia. IMPACT: Because there is no safe level of exposure to benzene, our results call for interventions to reduce or prevent hookah tobacco use, regulatory actions to limit hookah-related exposure to toxicants including benzene, initiate labeling of hookah-related products, and include hookah smoking in clean indoor air legislation.

Providing coaching and cotinine results to preteens to reduce their secondhand smoke exposure: a randomized trial.

BACKGROUND: Secondhand smoke exposure (SHSe) poses health risks to children living with smokers. Most interventions to protect children from SHSe have coached adult smokers. This trial determined whether coaching and cotinine feedback provided to preteens can reduce their SHSe. METHODS: Two hundred one predominantly low-income families with a resident smoker and a child aged 8 to 13 years who was exposed to two or more cigarettes per day or had a urine cotinine concentration ≥ 2.0 ng/mL were randomized to control or SHSe reduction coaching groups. During eight in-home sessions over 5 months, coaches presented to the child graphic charts of cotinine assay results as performance feedback and provided differential praise and incentives for cotinine reductions. Generalized estimating equations were used to determine the differential change in SHSe over time by group. RESULTS: For the baseline to posttest period, the coaching group had a greater decrease in both urine cotinine concentration (P = .039) and reported child SHSe in the number of cigarettes exposed per day (child report, P = .003; parent report, P = .078). For posttest to month 12 follow-up, no group or group by time differences were obtained, and both groups returned toward baseline. CONCLUSIONS: Coaching preteens can reduce their SHSe, although reductions may not be sustained without ongoing counseling, feedback, and incentives. Unlike interventions that coach adults to reduce child SHSe, programs that increase child avoidance of SHSe have the potential to reduce SHSe in all settings in which the child is exposed, without requiring a change in adult smoking behavior.

The reliability and practicality of the Arkansas method assay of isoniazid adherence.

The Arkansas method (AM) for isoniazid (INH) metabolite detection is a relatively inexpensive, simple, objective measure of adherence. The purpose of the study was to explore whether variations in urine sample handling and storage will produce accurate assay outcomes. Participants were a convenience sample of 28 adults and adolescents prescribed INH for latent tuberculosis infection. Participants provided one sample to test effects of the following: mixing processes; durations at room temperature, in a refrigerator, or frozen; and effects of freeze/thaw cycles on AM outcomes. No manipulations had a discernible impact on outcomes with concordant positive rates from 85% to 100%. Concordance rates of manipulated samples did not appear to differ from rates of norm samples. Results suggest that urine samples can withstand a variety of manipulations in both handling and storage without affecting the accuracy of AM assay results. These findings have important implications for providers of treatment and researchers and provide the impetus for both to examine the potential of using the AM of INH metabolite testing as a measure of medication adherence.