Objective Characterise the vaginal metabolome of cervical HPVinfected and uninfected women.Design Cross-sectional.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 HPVwomen after adjustment for CST and cigarette smoking. Metabolomic profiles of HPV + and HPV À 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 HPVwomen. In CST IV, there were lower concentrations of glutathione, glycogen, and phospholipid-related metabolites in HPV + participants than in HPVparticipants. 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). ConclusionsThe vaginal metabolome of HPV + women differed from HPV À 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. Keywords 16S rRNA gene amplicon sequencing, human papillomavirus, vaginal metabolome, vaginal microbiota. Tweetable abstract Metabolomics study: Vaginal microenvironment of HPV + women may be informative for nonsurgical interventions. Please cite this paper as: Borgogna JC, Shardell MD, Santori EK, Nelson TM, Rath JM, Glover ED, Ravel J, Gravitt PE, Yeoman CJ, Brotman RM. The vaginal metabolome and microbiota of cervical HPV-positive and HPV-negative women: a cross-sectional analysis.
SUMMARY Aging in men is associated with loss of bone mass, impaired physical function and altered body composition. The objective of this proof-of-concept randomized, double-blind, placebo-controlled, parallel-group, single-center trial was to determine the relative effects of testosterone (T) and estradiol (E2) on bone mineral density, body composition, and physical performance in older men. The primary outcome was lumbar spine bone mineral density (BMD), and secondary outcomes were body composition, muscle strength, gait speed, and sex hormone concentrations. Forty three men (age range, 65–82 years; mean age 71 years) with low total T levels <350 ng/dL were randomized to one of three groups: 5 g transdermal testosterone gel (TT) (N = 16), anastrozole (AI) 1 mg (N = 14) or placebo daily (N = 13) for 12 months. Outcomes were assessed at baseline, 3, 6, and 12 months. Both TT and AI increased serum TT levels (>500 ng/dL, p < 0.05) compared to baseline; T values remained stable throughout the duration of the trial. At 12 months, TT improved the primary outcome of lumbar spine BMD (p < 0.01). Both interventions improved knee strength at 12 months compared to baseline (p < 0.05) while lean body mass significantly increased only in the AI group at 6 and 12 months (1.49 ± 0.38 kg, p < 0.01; 1.24 ± 0.39 kg, p < 0.05, respectively) compared to baseline. Interestingly, TT improved fast gait speed at 3 and 12 months (p < 0.01, p < 0.05, respectively). In summary, this proof-of-concept study confirms that aromatization of T is required for maintaining BMD in older men with low-T levels. The trial also uncovered the novel finding that aromatization of T is required for improvement in fast gait speed, an observation that needs to be verified in future studies.
AL. Cluster-randomized trial of a mobile phone personalized behavioral intervention for blood glucose control. Diabetes Care 2011;34:1934-1942 In the article listed above, the values for the 9-month glycated hemoglobins are incorrect due to a programming error. The significance of the results and the discussion remained unchanged. The changes to Table 1 and to the text are detailed below. 1) In the abstract (page 1934) of the article, under RESULTS, it reads "a difference of 1.2% (P , 0.001) over 12 months." This should read "a difference of 1.2% (P 5 0.001) over 12 months." 2) In the RESULTS section of the text (page 1939), the following changes to the text should be made: a) "(95% CI 0.6-1.8%; P , 0.001)" should read "(95% CI 0.5-1.9%; P 5 0.001)." b) "Both had greater 12-month glycated hemoglobin reductions than UC (CO, P 5 0.02; CPP, P 5 0.45)" should read "Both had greater 12-month glycated hemoglobin reductions than UC (CO, P 5 0.027; CPP, P 5 0.40)." c) "... stratum with baseline glycated hemoglobin ,9.0% (difference in decrease 0.7%, 95% CI 0.2-1.1, P 5 0.003) and the stratum with baseline glycated hemoglobin at least 9.0% (difference in decrease 1.3%, 0.2-2.4, P 5 0.01)" should read "... stratum with baseline glycated hemoglobin ,9.0% (difference in decrease 0.7%, 95% CI 0.1-1.3, P 5 0.006) and the stratum with baseline glycated hemoglobin at least 9.0% (difference in decrease 1.3%, 95% CI 0.1-2.7, P 5 0.017)." d) "The test of interaction was not significant (P 5 0.49) for baseline glycated hemoglobin stratum and treatment group over time" should read "The test of interaction was not significant (P 5 0.27) for baseline glycated hemoglobin stratum and treatment group over time."3) In the CONCLUSIONS section of the text (page 1940), "a difference of 1.2% (P , 0.001) over 12 months" should read "a difference of 1.2% (P 5 0.001) over 12 months
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