Do menthol smokers inhale more nicotine and toxins?

I have previously discussed some studies conducted at UMDNJ suggesting that under certain conditions menthol smokers inhale more nicotine and carbon-monoxide from their cigarettes and have a lower quit rate when attending our tobacco dependence treatment clinic.

The pattern of results we have observed suggest that it may not be a simple effect of menthol causing smokers to inhale more smoke. Rather, we have proposed that in circumstances requiring the smoker to reduce their cigarette consumption (e.g. when price increases affect affordability in a low-income smokers) menthol enables the smoker to increase the amount of smoke and nicotine they inhale per cigarette, by reducing the harshness.

Now clearly manufacturers of menthol cigarettes have an interest in this issue. In particular, the Lorrilard Tobacco Company, who depend on sales of Newport cigarettes for most of their profits, have an interest. So I was interested to read a paper by Dr Daniel Heck of Lorrilard Tobacco Company, on biomarkers of smoke exposure on menthol and nonmenthol smokers.

The study recruited 54 monthol smokers and 58 non-menthol smokers, provided them with preference-matched standard menthol or nonmenthol for a 1-week study period and menthol smokers were also given free menthol cigarettes for 2 weeks prior to the study period to allow them to acclimatize to the study menthol cigarettes.

For one day at the start of the one week study period and another day at the end, participants were allowed to smoke normally but blood and urine was taken in order to measure a variety of indicators of smoke exposure. The main result was that there were no consistent differences in markers of smoke exposure between menthol and nonmenthol smokers.

I am not writing to dispute the findings or even the measures used in the study (although Id have preferred if blood nicotine concentration had been measured). Rather I want to point out some characteristics of the study population and study procedures that make it unsurprising that they didn’t find any differences.

First of all, the study sample smoked an average of 27 cigarettes per day (both menthol and nonmenthol smokers). This a very high cigarette consumption, and extremely unusual for current African American menthol cigarette smokers. Just for comparison, among smokers attending our clinic (who are heavier than average smokers), AA menthol smokers smoked under 16 cigarettes per day.

Secondly, providing the sample of menthol smokers with free access to the study menthol cigarettes for 3 weeks, including the study week, detracts from the financial reality facing many smokers just now, and could have altered the way they smoked the cigarettes.

It is a pity this study did not recruit a more representative sample of US smokers and allow them to smoke their own, paid-for cigarettes.


Heck JD. Smokers of menthol and nonmenthol cigarettes exhibit similar levels of biomarkers of smoke exposure. Cancer Epidemiol Biomarkers Prev. 2009 Feb;18(2):622-9.

Labels: biomarkers, cancer, cigarette, cigarette smoking, jonathan foulds, menthol, toxins

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Does nicotine cause cancer?

Every now and again we see a new newspaper headline claiming that nicotine causes some serious health problem, whether it be heart attacks or cancer. Usually the headline is based on a very small study in humans, or a laboratory study of cells in a petri dish or test tube. In the past week we saw the latest example. A study by Gemenetzidis and colleagues in London examined the effect of nicotine on a protein transcription factor named FOX-1 in tissue cells in the laboratory. Fox-1 expression has been associated with onset of tumor growth in prior studies. The study found that nicotine application to cells in the lab resulted in an increase in Fox-1 expression (in the laboratory, not in humans). The authors therefore concluded that nicotine , by stimulating FOX-1 expression, may promote cell instability and tumor growth.

The thing that is relatively new about this finding is that many prior studies and reviews have concluded that nicotine does not play a part in stimulating tumor development or growth. So for this study to claim that nicotine causes cancer is contrary to previous expert opinion.

I am not a cell biologist and cannot claim to fully understand the science contained in this recent publication by Gemenetzidis and colleagues. However, I can think of some ways of assessing whether the laboratory finding really does translate into health effects in the real world. In many countries around the world people use smokeless oral tobacco for most of their adult life. Oral smokeless tobacco delivers high quantities of nicotine (in addition to other proven carcinogens), but without delivering any smoke. In Sweden there is a tradition of men using a form of smokeless tobacco, called snus, that is relatively low in other toxins. So if nicotine really does have a role in increasing oral cancer risk, we would assume that people using this nicotine delivery product throughout their whole life would have an increased oral cancer risk. However, numerous long term epidemiological studies of Swedish men who use this oral tobacco product have found that they do not have an increased rate of oral cancer, as compared with men who never used any tobacco products.

Gemenetzidis and colleagues, on the basis of their lab study of cells in the lab, have cautioned against the use of nicotine replacement therapy in case it causes cancer. Now nicotine replacement therapy is typically used for up to 12 weeks, but occasionally for longer. But NRT typically delivers lower levels of nicotine than snus smokeless tobacco and is almost never used in a lifelong fashion ….daily from teenage years for life, as is common for smokeless tobacco. So to my way of reading the epidemiological evidence, if lifelong use of high nicotine oral tobacco does not increase the risk of oral cancer, then the risk that a few months of NRT use will cause oral cancer are non-existent. So no, I don’t believe that this study provides convincing evidence that nicotine causes cancer.

Sometimes I wish that lab scientists would check out the epidemiological evidence before announcing to the press that effective therapies may cause cancer.


Example article last week in the London Times:
http://www.timesonline.co.uk/tol/life_and_style/health/article6143744.ece

The full study report can be viewed at:
http://dx.plos.org/10.1371/journal.pone.0004849

For a very thorough review of the health effects of nicotine, and of smokeless tobacco, check out the relevant chapters of the recent Royal College of Physicians report on tobacco harm reduction at:
http://www.rcplondon.ac.uk/pubs/brochure.aspx?e=234

Labels: cancer, jonathan foulds, nicotine, NRT

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Winston Man Landers dies of smoking-caused cancer

Alan Landers, who became famous as a model in advertisements for Winston cigarettes, died of complications of cancer of the larynx on February 27th, after surviving lung cancer and heart disease that he also attributed to his previous heavy smoking.

Alan Landers, though once a promoter of cigarettes, then became an anti-tobacco advocate and in 1995 he sued the tobacco industry for his smoking-caused illnesses. His case was due to be heard in court in April, but like so many in that situation, he passed away before his case could be decided.

Click here for his obituary in the New York Times: http://www.nytimes.com/2009/03/04/us/04landers.html
You can learn more about his life and anti-tobacco work at his website: http://winstonman.com/
Of course Alan Landers is one of many who starred in advertisements for cigarettes but who subsequently contracted or died from smoking caused diseases, including at least one Marlboro man.

His death serves as a reminder that although cigarettes have been portrayed as a glamorous life-style choice, in reality they are a deadly addiction.

Labels: alan landers, cancer, death, jonathan foulds, winston man

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What is in cigarette smoke?

More than 4000 different chemicals have been identified in cigarette smoke. Most of us have a very basic idea that these chemicals can be harmful to health and that the mechanisms whereby this complex mixture of toxins contained in tobacco smoke leads to specific diseases are complex. However, I thought it might be helpful to some readers to provide a very basic description of the ways in which some of these components of cigarette smoke cause ill-health.

The simplest categorization of the components if cigarette smoking identifies 3 major components: tar, nicotine, and cabon-monoxide (CO).

Tar is the black sticky mass that coats the lungs and the airways. There are many hundreds of different chemicals within the tar, some of which have been shown to be carcinogenic in animals and/or humans. The deposition of particles of tar in the lungs and upper airways leads to the blocking of airways and to serious breathing problems, including Chronic Obstructive Pulmonary Disease (COPD). The toxic chemicals also cause inflammation and reduce the elasticity of the lungs and hence the ability to inhale and exhale normally.

The carbon-monoxide in smoke replaces oxygen in the hemoglobin (a component of blood), adversely affecting oxygen transport and energy supply, and requiring the heart to do more work to supply the same amount of oxygen to the body. A large number of smoke constituents, and particularly components of the gaseous phase of the tobacco smoke, cause immunologic responses and inflammation in the cells. This causes increased stickiness of the blood which increases the risk of clots. These processes increase the likelihood of a heart attack, stroke or other problems with the cardiovascular system.

Irritants such as nitric oxide cause hypersecretion of mucus and substances such as acrolein, acetone and acetaldehyde cause damage to the small hair-like strands that line the airways (cilia). This damage to the cilia impairs the ability of the cilia to clear mucus, causing breathi9ng difficulties. Years of smoking and daily coating of the lungs and airways in tar leads to irreversible lung damage and ultimately death from COPD .

Acute nicotine (critical for the development of addiction), increases heart rate, blood pressure and causes peripheral vasoconstriction (i.e. impairs peripheral circulation and thus exacerbates Reynauds’ Disease and erectile dysfunction). However, studies of smokeless tobacco users (who have high nicotine exposure like smokers, but without the smoke) compared with smokers, suggest that most of the cardiovascular problems are not caused by nicotine. It therefore appears that it is the thrombogenic effects of tobacco smoke exposure (primarily oxidant gases), combined with reduced oxygen supply (carbon monoxide) and increased myocardial oxygen demand (nicotine) that cause the cardiovascular harms from smoking.

Some of the chemicals found in cigarette smoke are listed below.

Carbonyls
Formaldehyde, Acetaldehyde, Acetone, Acrolein, Propionaldehyde, Crotonaldehyde, Methyl-Ethyl-Ketone, Butyraldehyde
Phenolics
Hydroquinone, Resorcinol, Catechol, Phenol, Cresol (m+p and o)
Aromatic Amines
3- and 4-aminobiphenyl, 1- and 2- aminonapthlene, o-toluidine, o-anisidine
Oxides of Nitrogen NO,
Hydrogen Cyanide
Ammonia
Volatiles
Benzene, Toluene, 1,3-butadiene, Isoprene, Acrylonitrile
Semi-Volatiles
Pyridine, Quinoline, Styrene
Trace Metals
Nickel (Ni), Cadmium (Cd) Lead (Pb) Chromium (Cr) Arsenic (As) Selenium (Se), Mercury (Hg)
Tobacco Specific Nitrosamines
N-Nitrosonornicotine (NNN)N-Nitrosoanabasine (NAB) Nitrosoanatabine (NAT)4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK)
Volatile Nitrosamines
N,N-Nitrosodimethylamine (NDMA)N-Nitrosopyrrolidine (NPYR), N,N-Nitrosodiethylamine (NDEA)N,N-Nitrosoethylmethylamine (NEMA), N,N-Nitrosodipropylamine (NDPA)N,N-Nitrosodibuthylamine (NDBA), N-Nitrosopiperidine (NPIP)
Polycyclic Aromatic Hydrocarbons
Naphthalene, 1-Methylnaphthalene, 2-methylnaphthalene, AcenaphthyleneAcenaphthene, Fluorene, Phenanthrene, Anthracene, FluoranthenePyrene, Benzo(a)anthracene, Chrysene, Benzo(b)fluorantheneBenzo(k)fluoranthene, Benzo(j)fluoranthene, Benzo(g,h,l)peryleneBenzo(e)pyrene, Benzo(a)pyrene, PeryleneIndeno(1,2,3,-cd)pyrene, Dibenzo(a,h)anthraceneDibenz(a,j)acridine, Dibenz(a,h)acridine, Dibenz(a,e)pyreneDibenz(a,h)pyrene, Dibenz(a,i)pyrene, Dibenz(a,l)pyrene7H-Dibenzo(c,g)carbazole,
Heterocyclic Aromatic Amines
2-Amino-3-methylimidaszo(4,5-f)quinoline (IQ)2-Amino-3,4-dimethylimidazo(4,5-f)quinoline (MeIQ)2-Amino-3-methyl-9H-pyrido(2,3-b)indole (MeAaC)2-Amino-9H-pyrido(2,3-b)indole (AaC)1-Methyl-9H-pyridol(3,4-b)indole (Harman)9H-Pyrido(3,4-b)indole (Norharman)

Labels: cancer, chemicals, cigarette, jonathan foulds, nicotine, smoke, tar, toxins

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Smoking, smokeless tobacco and cancer (2)

My previous post discussed toxin delivery from different tobacco products. Now what is the evidence relating use of these products to health problems? Unfortunately most studies don’t collect data on different brands or even categories of smokeless tobacco being used, and few compare directly the risks from smokeless with those from smoking. However, we can get a sense of the risks by examining studies based in different parts of the world where different types of tobacco are used. When we look at it this way we can find very clear evidence that the types of smokeless tobacco used in Sudan and India increase the risk of oral cancer. There is also toxicological evidence showing that Sudanese smokeless tobacco has very high concentrations of TSNAs (carcinogenic toxins), as do some forms of smokeless tobacco used in India. In Asia the picture is complicated by the tradition of adding other ingredients, especially areca nut which is highly carcinogenic on its own.

Then when we look at studies of smokeless tobacco use from the U.S. we see mixed results. One particular study published in the 1980s found very high risks of oral cancer. That study by Professor Deborah Winn and colleagues focused on women in southern United States and found that white never-smoking women (who tend to use oral dry snuff powder) had a relative risk of over 4.2 (2.6-6.7), for developing oral and pharyngeal cancer. Women who had used smokeless tobacco for 50 years had a 50-fold increase in risk for some oral cancers. It should be noted that only a tiny minority of smokeless users use the type of dry snuff tobacco that is commonly used by women in these rural parts of North Carolina. It should also be noted that the type of smokeless tobacco with the extremely high concentration of toxins mentioned in my previous post was also a type of dry snuff. So it begins to look like it’s the smokeless tobacco with very high toxin levels that has evidence of a causal effect on oral cancer. In fact, one of the largest studies on the effects of smokeless tobacco use in the United States (by the American Cancer Society) found no significant increase in the risk for oral cancer among smokeless tobacco users. One of these studies examined a population of 2488 smokeless tobacco users with a median age of 57 at enrolment (i.e. they'd used smokeless for decades) and followed them up 18 years later (i.e. mean age 75). This study found only one death from oral cancer in exclusive smokeless tobacco users, and none in former users, which was a slightly lower rate than occurred in people who had never used any tobacco in their life. These findings from the American Cancer Society suggest that any effect of commonly used brands of smokeless tobacco in the United States on oral cancer, if present, is relatively small.

Finally, we can examine the studies conducted in Sweden where the use of a form of low-toxin moist snuff (called snus) is more common than smoking in men. These studies consistently find no increased risk of oral cancer for snus users. One of the best of these studies was published in the Lancet recently and found that snus users have no increased risk of oral or lung cancer, but they have twice the risk of pancreatic cancer of never tobacco users. That same study found higher risks of all these cancers in smokers (e.g. smokers were about 10 times more likely to get lung cancer than either snus users or never tobacco users, who both had similar risks).

So now lets come back the recent report by Hecht and colleagues. It found similar concentrations of a specific carcinogen in smokeless users and smokers. But we have excellent data showing that smokers have much higher risks of lung cancer than smokeless users, and also higher risks of oral cancer than users of some forms of smokeless tobacco. The lung cancer pattern suggests that deposition of carcinogens directly into the lungs is relevant to the causal mechanism as smokeless tobacco has generally not been found to cause lung cancer in humans. But then we also have a higher risk of oral cancer for smokers. This causes one to consider whether the biomarker being measured in the urine in Hecht and colleague's study is very closely linked to the mechanism wherbye tobacco causes cancer in humans. Perhaps there are other toxins (e.g. benzo(a)pyrene) that are important in triggering cancer in smokers, but are found in lower levels in smokeless users? Whatever, the explanation, it seems that urine NNAL levels do not relate very closely to cancer risks in tobacco users.

But when discussing health risks from tobacco we need to be clear that these involve much more than lung or oral cancer, but also other cancers, and also other serious respiratory and cardiovascular diseases. For most of these, the health risks from smoking greatly outweigh the risks from smokeless tobacco. Chronic respiratory diseases are extremely common among smokers but there is neither good evidence nor a plausible rationale linking use of smokeless tobacco to these respiratory diseases.

So although it is clear that smokeless tobacco contains carcinogens and is not harmless, it is significantly less harmful than smoking cigarettes. I agree with Hecht and colleagues that we should not encourage anyone to use smokeless tobacco, when we have safe and effective medicines to help them quit smoking. However, I think we need to be able to give an honest answer to the question, “Are there forms of smokeless tobacco that are much less likely to kill me than smoking cigarettes?”. The honest answer is,”yes”. Similarly, of we are asked whether some types of smokeless tobacco may be less harmful than others, it seems prudent to suggest that some types of tobacco that have higher concentrations of toxins than others, and that the type of smokeless tobacco used in Sweden (snus) appears to be lower in toxins and health risks than much of the tobacco used in the rest of the world. It is far from risk-free (as are many things that people choose to do on a regular basis, like driving a car, eating donuts, drinking beer, mountain-climbing, or having sex), but experts agree that it is about 90% less harmful than smoking:
http://cebp.aacrjournals.org/cgi/content/full/13/12/2035
Similarly, given the relationship between toxin delivery and health effects from smokeless tobacco, it would seem to be sensible to regulate tobacco products in a manner that requires manufacturers to minimize the concentrations of toxins delivered as much as is technically possible.

In the mean time (and also after regulation is in place), manufacturers who produce and market products containing and delivering unnecessarily high quantities of toxins should be legally liable for the effects of their defective products.

Labels: cancer, smokeless, Smoking, tobacco

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Carcinogens from smoking and smokeless tobacco use (1)

This month an interesting study by Professor Stephen Hecht and colleagues at University of Minnesota was published in the journal, Cancer Epidemiology, Biomarkers & Prevention. The study compared cigarette smokers with smokeless tobacco users on their urine concentration of a biomarker of nicotine intake (cotinine, the main metabolite of nicotine), and a biomarker of exposure to a known carcinogen (NNAL, a biomarker of NNK exposure). The study found that the smokeless tobacco users had higher concentrations of the nicotine metabolite and higher concentrations of the carcinogen biomarker than smokers. The authors concluded that smokeless tobacco is not a safe substitute for smoking.

The authors are correct in this conclusion, as some forms of smokeless tobacco have been shown to be associated with oral cancer, other oral lesions, and may also increase some cardiovascular risks. The idea that smokeless tobacco is not safe is unlikely to be surprising to many people. But given that many of the major cigarette manufacturers are currently test-marketing smokeless tobacco products it may be worth examining the types and risks from smokeless tobacco in more detail, and also looking at how the epidemiological data relates to the recent findings from Hecht and colleagues.

The first thing that needs to be said about smokeless tobacco is that it is not just one thing. The extremely wide variety of different types of smokeless tobacco can be viewed on an excellent website produced by the U.S. National Cancer Institute and Centers for Disease Control, online at: www.cancercontrol.cancer.gov/tcrb/stfact_sheet_combined10-23-02.pdf.

Secondly, smokeless tobaccos vary enormously in the amount of toxins (including carcinogens) they deliver, and (not surprisingly) the ones containing higher concentrations of toxins (like carcinogenic tobacco-specific nitrosamines, or benzo(a)pyrene), appear to be more likely to have adverse health effects. To give an idea of the range of concentrations of toxins, Professor Brad Rodu at University of Louisville published data on the concentration of carcinogenic Tobacco-Specific Nitrosamines (TSNAs) in various smokeless tobacco products. Some examples are as follows (the units of measurement are parts per million based on dry weight):

Ariva (new powdered tobacco lozenge): <0.1 ppms
Ettan (Swedish snus): 2.0 ppms
Red Man (US chewing tobacco): 1.8 ppms
Copenhagen (leading US moist snuff): 12.1 ppms
Red Seal (US dry snuff): 1096 ppms

So we have here over a thousand-fold difference in the concentration of certain toxins in different types of smokeless tobacco! There are a few additional problems. Most of the smokeless tobacco products sold in the United States use fermentation in their production. This facilitates the development of carcinogenic compounds in the tobacco. In fact there is evidence to show that in these fermented products, they continue to ferment in the can, such that the concentration of carcinogens may increase in the can as it sits on the shelf. The method of production used for Swedish snus does not include fermentation, but rather uses a pasteurization-like process that treats the product with steam and appears to kill the microbes required for fermentation. This is thought to be the reason why Swedish snus has lower levels of carcinogens than US Smokeless tobacco. It may also be the reason that Swedish snus does not appear to cause oral cancer. However, the problem remains in the United States that the tobacco manufacturers can adjust the way they produce their products and the ingredients included in them without telling anyone. That is part of the reason why many experts support the pending legislation that would give the FDA the power to regulate tobacco products. This legislation appears to enable the FDA to require maximum permissible levels of harmful toxins in both smoked and smokeless tobacco products. With cigarettes the problem of what happens when you burn the product and inhale the smoke remains, but for smokeless there is a real prospect of offering a product that contains and delivers a known maximum level of toxins – and potentially a level that would be extremely unlikely to cause cancer. But for now, as demonstrated in Hecht and colleagues study, US smokeless tobacco delivers more toxins than necessary and there is little we can do about it.

In my next post I’ll discuss the relationship between the concentration of toxins in smokeless tobacco products and their harmfulness to health.

If you are interested in the views of tobacco and cancer experts on this topic you can learn more by reading the article linked below:
http://cebp.aacrjournals.org/cgi/content/full/13/12/2035

Labels: cancer, cigarette smoking, smokeless, tobacco

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Is cannabis smoking more harmful than cigarette smoking?

A study published in the journal, Thorax, recently hit the headlines as demonstrating that smoking a cannabis joint was at least twice as harmful to lung function as smoking a cigarette. So what are the dangers of smoking cannabis and how do these risks compare to those of smoking tobacco?

Firstly, we can’t ignore the fact that in most places and circumstances possession of cannabis is a criminal offence with potentially serious legal consequences and testing positive for cannabis use in the workplace can seriously harm your career. That being said, it is difficult to tease out the health effects of cannabis smoking, partly because almost all cannabis smokers are or have been tobacco smokers as well. The recent study compared lung effects on four groups, each consisting of around 80 volunteers: 1. Cannabis users (at least a joint a day for 5 years), 2. Cigarettes only smokers (at least 20 per day for at least a year), 3. Those who smoke both cigarettes and cannabis and 4. Never smokers. When they scanned the lungs for evidence of emphysema they found that only 1% of the cannabis only users had emphysema, as did 19% of the cigarette smokers, 16% of those using both cigarettes and cannabis and 0% of the never smokers. This appears to show that although cannabis smoking worsens lung function, structural damage is common only with cigarette smoking. This finding likely reflects the different ways in which the products are used. A cannabis joint is typically smoked with greater intensity, with larger puff volumes and breath holding, leading to greater smoke and carbon-monoxide exposure than from a single cigarette (hence the greater impact on lung function on a per-smoke basis). However, while most regular cannabis smokers will smoke less than 5 joints per day, most regular cigarette smokers will typically smoke over 15 cigarettes per day. So the overall smoke exposure is typically much greater with tobacco than with cannabis and this is a likely reason for the greater occurrence of tobacco-caused illness.

Chronic cannabis use is associated with the following health effects:
Increased risk of developing a psychotic illness
Respiratory diseases (e.g. bronchitis) and impaired lung function
Dependence (and an associated withdrawal syndrome)
Subtle disturbances of memory and attention
Cannabis use may also be associated with other health problems (e.g. lung cancer, and birth defects in children whose mother smoked cannabis during pregnancy) but the evidence is less clear for these problems.

Tobacco smoking, on the other hand, has been proven to cause a long list of diseases, including the three main causes of premature death: lung cancer, COPD and cardiovascular diseases. The status of tobacco as a legal form of drug use, its less marked psychological effects (e.g. not impairing judgment and driving ability), and the relatively short half-life of the active ingredient (nicotine half-life= 2 hours, versus days for THC) all lead to the tendency for users to take it very frequently (e.g. 15-20 cigarettes per day) and for a very long time (typically starting in teenage years and continuing daily into old age). Cannabis, on the other hand, is more commonly used either less than daily or once or twice per day, and users typically cease use prior to middle age.

So if one is to compare the health effects under typical use conditions, tobacco smoking is much more harmful to health. However, if one were to compare the effects on a “per smoke” basis then the two are likely of similar harmfulness, with cannabis having greater adverse psychological effects.

The human body was not built to inhale smoke of any kind, and whether it’s the result of burning tobacco, cannabis or lettuce, inhalation will cause damage in proportion to the quantity inhaled.

Labels: cancer, cannabis, emphysema, marijuana, psychosis

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