The vaginal metabolome and microbiota of cervical HPV-positive and HPV-negative women: a cross-sectional analysis.

OBJECTIVE: Characterise the vaginal metabolome of cervical HPV-infected and uninfected women. DESIGN: Cross-sectional. SETTING: The Center for Health Behavior Research at the University of Maryland School of Public Health. SAMPLE: Thirty-nine participants, 13 categorised as HPV-negative and 26 as HPV-positive (any genotype; HPV+ ), 14 of whom were positive with at least one high-risk HPV strain (hrHPV). METHOD: Self-collected mid-vaginal swabs were profiled for bacterial composition by 16S rRNA gene amplicon sequencing, metabolites by both gas and liquid chromatography mass spectrometry, and 37 types of HPV DNA. MAIN OUTCOME MEASURES: Metabolite abundances. RESULTS: Vaginal microbiota clustered into Community State Type (CST) I (Lactobacillus crispatus-dominated), CST III (Lactobacillus iners-dominated), and CST IV (low-Lactobacillus, 'molecular-BV'). HPV+ women had higher biogenic amine and phospholipid concentrations compared with HPV- women after adjustment for CST and cigarette smoking. Metabolomic profiles of HPV+ and HPV- women differed in strata of CST. In CST III, there were higher concentrations of biogenic amines and glycogen-related metabolites in HPV+ women than in HPV- women. In CST IV, there were lower concentrations of glutathione, glycogen, and phospholipid-related metabolites in HPV+ participants than in HPV- participants. Across all CSTs, women with hrHPV strains had lower concentrations of amino acids, lipids, and peptides compared with women who had only low-risk HPV (lrHPV). CONCLUSIONS: The vaginal metabolome of HPV+ women differed from HPV- women in terms of several metabolites, including biogenic amines, glutathione, and lipid-related metabolites. If the temporal relation between increased levels of reduced glutathione and oxidised glutathione and HPV incidence/persistence is confirmed in future studies, anti-oxidant therapies may be considered as a non-surgical HPV control intervention. TWEETABLE ABSTRACT: Metabolomics study: Vaginal microenvironment of HPV+ women may be informative for non-surgical interventions.

Cigarette smoking is associated with an altered vaginal tract metabolomic profile.

Cigarette smoking has been associated with both the diagnosis of bacterial vaginosis (BV) and a vaginal microbiota lacking protective Lactobacillus spp. As the mechanism linking smoking with vaginal microbiota and BV is unclear, we sought to compare the vaginal metabolomes of smokers and non-smokers (17 smokers/19 non-smokers). Metabolomic profiles were determined by gas and liquid chromatography mass spectrometry in a cross-sectional study. Analysis of the 16S rRNA gene populations revealed samples clustered into three community state types (CSTs) ---- CST-I (L. crispatus-dominated), CST-III (L. iners-dominated) or CST-IV (low-Lactobacillus). We identified 607 metabolites, including 12 that differed significantly (q-value < 0.05) between smokers and non-smokers. Nicotine, and the breakdown metabolites cotinine and hydroxycotinine were substantially higher in smokers, as expected. Among women categorized to CST-IV, biogenic amines, including agmatine, cadaverine, putrescine, tryptamine and tyramine were substantially higher in smokers, while dipeptides were lower in smokers. These biogenic amines are known to affect the virulence of infective pathogens and contribute to vaginal malodor. Our data suggest that cigarette smoking is associated with differences in important vaginal metabolites, and women who smoke, and particularly women who are also depauperate for Lactobacillus spp., may have increased susceptibilities to urogenital infections and increased malodor.

Bupropion for smoking cessation : predictors of successful outcome.

OBJECTIVES: To identify predictors of smoking abstinence at the end of medication use that could assist in the optimal use of a sustained-release (SR) form of bupropion for treating cigarette smokers. DESIGN: A double-blind, placebo-controlled, dose-response trial. SETTING: Multicenter (three sites) study conducted in the United States. PARTICIPANTS: Six hundred fifteen healthy men and women (> or = 18 years of age) who were smoking > or = 15 cigarettes per day and who were motivated to stop smoking. INTERVENTION: Random assignment of patients to placebo or SR bupropion treatment, 100, 150, or 300 mg/d, for 7 weeks (total duration of study was 52 weeks: 7 weeks of treatment and 45 weeks of follow-up). MEASUREMENTS AND RESULTS: Logistic regression was used to identify predictors of abstinence at the end of the medication phase. Univariate predictors included the following: bupropion dose (p < 0.001); older age (p = 0.024); lower number of cigarettes smoked per day (cpd) (p < 0.001); lower Fagerström Tolerance Questionnaire score (p = 0.011); longest time previously abstinent that was < 24 h or > 4 weeks (p < 0.001); absence of other smokers in the household (p = 0.021); greater number of previous stop attempts (p = 0.019); and study site (p = 0.004). Multivariate predictors of abstinence at the end of the medication phase were the following: higher bupropion dose (p < 0.001); lower number of cpd (p < 0.001); longest time previously abstinent from smoking (p = 0.002); male gender (p = 0.014); and study site (p = 0.021). CONCLUSION: Bupropion SR therapy was effective in treating cigarette smokers independently of all other characteristics studied. Lower smoking rate, brief periods (ie, < 24 h) or long periods (ie, > 4 weeks) of abstinence with previous attempts to stop smoking, and male gender were predictive of better outcomes, independent of the dose of bupropion that was used.

Proposed definition of a smokeless tobacco user based on "potential" nicotine consumption.

This study examined and operationally defined "light," "moderate," and "heavy" users of smokeless tobacco according to the potential amounts of nicotine consumed per week from chewing tobacco and/or snuff products. Fifty adult male smokeless tobacco users ranging in ages from 18-85 were tested to determine nicotine content of smokeless tobacco products consumed. The smokeless tobacco products were blindly analyzed by gas chromatography to determine nicotine content. Mean nicotine yield per week was calculated by multiplying the number of cans and/or pouches used per week and placed on a normal probability distribution. The mean nicotine yielded 238 mg/wk and the categories emerged as "light" less than or equal to 87 mg/wk, "moderate" 88-388 mg/wk and "heavy" users greater than or equal to 389 mg/wk. Differences regarding type of user (light, moderate, heavy) were crossed tabbed with educational levels, years of smokeless tobacco use, age the habit was initiated, perception of harm and whether habit forming, and reason for using smokeless tobacco.

Personality profiles associated with smokeless tobacco use patterns.

The purpose of this study was to examine the personality characteristics of male dippers and chewers of smokeless tobacco. The study objective was to determine any differences in personality characteristics between dippers and chewers of smokeless tobacco and nonusers. A survey at a southeastern university provided a sample of 289 males, of which 55 (19%) were smokeless tobacco users. Each subject was administered a demographic data sheet and Cattell's Sixteen Personality Factor Questionnaire (16 PF). Smokeless tobacco users were categorized as snuff dippers or tobacco chewers, and comparisons of personality characteristics were made between persons who exclusively dipped, persons who exclusively chewed, persons who dipped and chewed, and persons who did neither. The results of the study indicated that smokeless tobacco use is primarily a White male habit; very few Blacks or other racial groups consumed smokeless tobacco among this population. Significant (p less than 0.05) personality differences between snuff dippers and tobacco chewers were noted. Snuff dippers were more socially outgoing, enthusiastic, imaginative and group dependent than chewers. Chewers were found to be more uncompromising, critical in outlook and practical and less easily influenced by others than dippers.

Pharmacologic treatments for the nicotine dependent smoker.

OBJECTIVE: To explore the biology of nicotine addiction and to investigate the latest pharmacological treatments for nicotine dependence. METHODS: Explore the research literature for treating nicotine dependence. RESULTS: Nicotine is an additive drug and the most effective methods for treating dependence are nicotine replacement therapy (NRT) and bupropion SR. CONCLUSION: The best available treatments for nicotine dependence are pharmacological adjuncts; specifically, NRT and bupropion SR when combined with behavioral counseling.

Smokeless tobacco use among American college students.

This study sought to delineate patterns of smokeless tobacco use among college students in the United States. A national sample (N = 5,894) of approximately equal numbers of men and women from 72 colleges and universities participated in the study. Eight percent of the college students in the Northeast used smokeless tobacco, whereas 15% in the South Central United States were using it. Seventeen percent of the American Indian, 14% of Mexican-American, 12% of white, and 4% of black students reported they had dipped or chewed. Smokeless tobacco users were more likely to have family and friends who also used smokeless tobacco. Almost two thirds (63%) of current users plan to continue to dip or chew. More than half (57%) the users consumed less than two cans or pouches per week. Smokeless tobacco is a serious problem in American colleges and universities. Unless prevention and cessation efforts target this group, the problem will continue to increase and ultimately could result in an oral cancer epidemic.

Screening for smokeless tobacco-associated lesions: recommendations for the dental practitioner.

The increasing use of smokeless tobacco and the accumulating list of associated health hazards including cancer and cardiovascular effects should be of concern to the dentist. This study documents both concern from patients' perceptions and clinical examinations of their smokeless tobacco-associated lesions. Implications for the dentists' practice among adolescents and young adults are discussed.

Smokeless tobacco use by youth in the U.S.

Oral snuff and chewing tobacco, commonly referred to as smokeless tobacco, are being used by many adolescent and young adult males, and no indication exists that use by this group is declining. Users are at risk for oral cancer, noncancerous oral pathology such as leukoplakias, and addiction. Information about patterns of smokeless tobacco use and motivations of users may help planners develop and implement interventions. Variables include the importance of peer and family influences, social image, knowledge of harmful effects, regional differences, use of other substances, and addiction. Due to the addictive nature of smokeless tobacco, older youth may need cessation programs. Health educators are encouraged to include smokeless tobacco in their tobacco use prevention programs and to develop and implement comprehensive tobacco interventions appropriate for their youth population.

Just a pinch between the cheek & gum.

At least in part, through a skillful manipulation of the public by the tobacco industry, the use of smokeless tobacco is rapidly increasing, especially among young male athletes and students in high school and colleges. Advertising implies that smokeless tobacco habits are innocuous and safe, but existing scientific evidence indicates that dipping and chewing are potentially harmful to one's health. Health professionals are urged to advise patients and students concerning the potential hazards of using smokeless tobacco. Further, health professionals should take a strong public stance in opposition to the current dipping and chewing advertising campaigns aimed at youth. These advertisements totally ignore the possible health hazards of smokeless tobacco. If the tobacco companies are allowed to continue to advertise smokeless tobacco in the same manner that they use to promote cigarette smoking, then some effort should be directed to require health warnings in these advertisements. In fact, some serious consideration should most likely be given to banning this new wave of tobacco marketing in the interest of public health, just as was the case with cigarette advertisements, especially in light of the fact that these ads are primarily targeted to young boys and men.

Implications of Smokeless Tobacco Use Among Athletes.

In brief: This literature review delineates the current status of smokeless tobacco. It discusses the prevalence and terminology as well as periodontal effects, buccal mucosal and soft-tissue alterations, leukoplakia, cancer, carcinogenic components, hemodynamic alterations, and potential addiction. It is clear that physicians and dentists should discourage their patients from using smokeless tobacco. Young people particularly may be influenced by popular sports figures and celebrities who convey the erroneous impression that smokeless tobacco is harmless.

Treating nicotine dependence.

To explore the biology of nicotine addiction and to discuss the latest effective treatments for nicotine dependence. Research indicates that the most effective methods for treating nicotine dependence are nicotine replacement therapy (NRT) and bupropion SR (BUP). We conclude that pharmacological adjuncts (NRT & BUP) achieve their greatest success when combined with behavioral counseling.

Immunogenicity and smoking-cessation outcomes for a novel nicotine immunotherapeutic.

NicVAX, a nicotine vaccine (3'AmNic-rEPA), has been clinically evaluated to determine whether higher antibody (Ab) concentrations are associated with higher smoking abstinence rates and whether dosages and frequency of administration are associated with increased Ab response. This randomized, double-blinded, placebo-controlled multicenter clinical trial (N = 301 smokers) tested the results of 200- and 400-µg doses administered four or five times over a period of 6 months, as compared with placebo. 3'AmNic-rEPA recipients with the highest serum antinicotine Ab response (top 30% by area under the curve (AUC)) were significantly more likely than the placebo recipients (24.6% vs. 12.0%, P = 0.024, odds ratio (OR) = 2.69, 95% confidence interval (CI), 1.14-6.37) to attain 8 weeks of continuous abstinence from weeks 19 through 26. The five-injection, 400-µg dose regimen elicited the greatest Ab response and resulted in significantly higher abstinence rates than placebo. This study demonstrates, as proof of concept, that 3'AmNic-rEPA elicits Abs to nicotine and is associated with higher continuous abstinence rates (CAR). Its further development as a treatment for nicotine dependence is therefore justified.