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.

The role of sexual networks in studies of how BV and STIs increase the risk of subsequent reinfection.

Prior studies have demonstrated that both bacterial vaginosis (BV) and sexually transmitted infections (STIs) are strong independent risk factors for subsequent STI. In observational studies of this biological enhancement (BE) hypothesis, it is important to adjust for the risk of STI exposure so that the independent effect of BE can be assessed. We sought to model if two markers of local sexual network (partner concurrency and cumulative number of STIs) represented residual confounding in the models of risk for subsequent infection in a study that screened 3620 women for STIs every 3 months for a year. Mixed-effects logistic regression was used to calculate the odds ratios for an incident diagnosis of Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis and BV following a diagnosis of any of these four at the prior visit, controlling for the cumulative number of STIs and partner concurrency variables. We found that partner concurrency and cumulative number of STIs were each associated with incident infection, and in general, controlling for these variables reduced the strength of the association between prior and incident infections. We conclude that the frequently found association between prior and incident STIs is associated with both BE and sexual network structure.

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.

Early Allograft Dysfunction After Liver Transplantation Is Associated With Short- and Long-Term Kidney Function Impairment.

Early allograft dysfunction (EAD) after liver transplantation (LT) is related to ischemia-reperfusion injury and may lead to a systemic inflammatory response and extrahepatic organ dysfunction. We evaluated the effect of EAD on new-onset acute kidney injury (AKI) requiring renal replacement therapy within the first month and end-stage renal disease (ESRD) within the first year post-LT in 1325 primary LT recipients. EAD developed in 358 (27%) of recipients. Seventy-one (5.6%) recipients developed AKI and 38 (2.9%) developed ESRD. Compared with those without EAD, recipients with EAD had a higher risk of AKI and ESRD (4% vs. 9% and 2% vs. 6%, respectively, p < 0.001 for both). Multivariate logistic regression analysis showed an independent relationship between EAD and AKI as well as ESRD (odds ratio 3.5, 95% confidence interval 1.9-6.4, and odds ratio 3.1, 95% confidence interval 11.9-91.2, respectively). Patients who experienced both EAD and AKI had inferior 1-, 3-, 5-, and 10-year patient and graft survival compared with those with either EAD or AKI alone, while those who had neither AKI nor EAD had the best outcomes (p < 0.001). Post-LT EAD is a risk factor for both AKI and ESRD and should be considered a target for future intervention to reduce post-LT short- and long-term renal dysfunction.

Prevalent high-risk HPV infection and vaginal microbiota in Nigerian women.

In this study, we evaluated the association between high-risk human papillomavirus (hrHPV) and the vaginal microbiome. Participants were recruited in Nigeria between April and August 2012. Vaginal bacterial composition was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V4) on Illumina MiSeq and HPV was identified using the Roche Linear Array® HPV genotyping test. We used exact logistic regression models to evaluate the association between community state types (CSTs) of vaginal microbiota and hrHPV infection, weighted UniFrac distances to compare the vaginal microbiota of individuals with prevalent hrHPV to those without prevalent hrHPV infection, and the Linear Discriminant Analysis effect size (LEfSe) algorithm to characterize bacteria associated with prevalent hrHPV infection. We observed four CSTs: CST IV-B with a low relative abundance of Lactobacillus spp. in 50% of participants; CST III (dominated by L. iners) in 39·2%; CST I (dominated by L. crispatus) in 7·9%; and CST VI (dominated by proteobacteria) in 2·9% of participants. LEfSe analysis suggested an association between prevalent hrHPV infection and a decreased abundance of Lactobacillus sp. with increased abundance of anaerobes particularly of the genera Prevotella and Leptotrichia in HIV-negative women (P < 0·05). These results are hypothesis generating and further studies are required.

A case control study of anovaginal distance and bacterial vaginosis.

We aimed to test the hypothesis that a short anovaginal distance may increase the risk of bacterial vaginosis (BV) due to faecal contamination and disruption of the vaginal microbiota. Women attending two sexually transmitted infection (STI) clinics in Baltimore, Maryland, USA, who complained of a vaginal discharge were asked to participate in a study to measure mucosal immune responses. In this pilot study of all enrolled women, a small plastic ruler was used to measure the anatomic distance from the posterior fourchette to the anus with the participant in the lithotomy position. Cases of BV, defined by Amsel's clinical criteria (n = 62), were compared with controls (n = 31) without BV. We used linear and logistic regression models to adjust for potential confounders. A total of 93 women were recruited (median age 28.6 years, 93% black, 4.4% gonorrhoea infection, 7.4% chlamydia infection, 8.6% trichomonas infection, 67% BV diagnosed). Mean anovaginal distance was 3.22 cm (SD: 0.74, range 1.8-5.2) for controls and 3.37 cm (SD: 0.76, range: 1.8-5.7) for cases (P = 0.38). There was no difference between cases and controls when comparing median values, quartiles and after adjusting for potential confounders. Among high-risk women with multiple co-infections, there was no association between anovaginal distance and clinical diagnosis of BV.

A comprehensive care program for pregnant addicts: obstetrical, neonatal, and child development outcomes.

This study reports the results of a comprehensive care program for pregnant addicts, one that provides medical, counseling, and child development services. Findings include the following. Women who enroll while pregnant generally stay through childbirth, and most deliveries are free of complication. Most newborns are of normal gestational age and birthweight, and these outcomes are directly related to length and amount of prenatal care. Neonatal withdrawal is directly related to prenatal maternal methadone dose. Child development, as measured by the Bayley Scales, is usually in the normal range, although mean scores for cognitive development decrease through age 2. Female babies generally have higher cognitive and motor scores than males, and their cognitive scores decline less sharply than those of the males. Developmental scores are directly related to neonatal maturity, especially birthweight. Prenatal maternal methadone dose tends to be negatively related to developmental scores for boys but not for girls.

Quality assurance programs in clinical trials.

Quality assurance programs attempt to assess the uniformity of compliance with a stated study program so that the results from one institution will indeed be comparable to those of all of the other institutions in the group. In the best situation, it should be easy to compare results from one group to those of any other group and any other studies of the same disease, because the basis of selection of the patient population, the treatment of patients, and the endpoints have been uniformly defined throughout. The evaluation of the end results includes a quantitative assessment of the appropriateness of these parameters. Quality assurance programs document the validity of interinstitutional, intergroup, and international studies. They are time-consuming and costly. They can be ulcerogenic. But, in the end, they are the firm basis upon which the statistical analysis can proceed.

Naltrexone and conventionality.

This study examines the effect of conventionality on whether patients who were scheduled for naltrexone took it, and on treatment outcomes for patients who did take it. It is based on admission and case record data for 147 male opiate addicts who enrolled in New York Medical College's Multitrack Abstinence Program. Naltrexone-taking is examined against an array of "drug" and "social" variables and is found to be strongly related to four in particular: amount spent daily on heroin, number of arrests, type of residence, and employment. These variables are combined into an index which measures a patient's degree of conventionality. It is found that naltrexone-taking varies directly with degree of conventionality. Furthermore, it is found that, among patients who took naltrexone, those who gained in conventionality while in treatment were more likely than others to leave the program opiate-free after terminating naltrexone therapy.

Female drug use: some observations.

This paper, based on a review of recent social science drug research, summarizes the main findings on female drug use and speculates on its future direction. The findings include the following: women are usually initiated into illicit drug use by men; rates of illicit drug use are lower among females than males (which may reflect the greater personal freedom traditionally granted to males), although the difference narrows among younger persons and among those who subscribe to more liberal values and life styles; women are more likely than men to use psychotherapeutic drugs (which may reflect strains resulting from their unequal status vis-à-vis men); and female opiate addicts, although they tend to hold conventional values, are often involved in such deviant activity as prostitution. To the extent that women gain social equality with men and subscribe to greater personal lifestyle freedom, they may be expected to show a higher rate of illicit drug use, particularly of a recreational kind. On the other hand, the rate of psychotherapeutic drug use may decrease, although if the tensions of the workplace eventually substitute for the tensions of status inequality, the resultant changes in rates and patterns of substance use are problematic.

Employment and social disability among opiate addicts.

This study examines the relationship between employment and social disability. It is based on admission data for 296 opiate addicts who enrolled in New York Medical College's Multitrack Abstinence Program during 1974. Social disability is defined here as an attribute of the patient which may count against him or her in the job market. Employment rates are examined in the light of an index comprised of three specific disabilities: minority group status, lack of a high school degree, and presence of an arrest record. It is found that the proportion of addicts employed upon admission to the program varies inversely with the number of disabilities. Furthermore, it is found that the proportion of addicts who rely on illegal acts for their main source of income varies directly with the number of disabilities.