Recent studies suggest that alterations in the female urinary microbiota is associated to development of bladder disease. However, the normal microbiota composition and variation in healthy women are poorly described. Moreover, the effects of hormonal changes on microbiota during menopause is not well understood. The aim of our study was to investigate the urinary microbiota in healthy pre- and postmenopausal women without urinary tract symptoms. Microbiota composition in catheterized urine samples was mapped using 16S rRNA gene sequencing. In total, 41 premenopausal and 42 postmenopausal women were initially included. Samples with first PCR amplification concentration below level of the negative control were excluded, resulting in 34 premenopausal and 20 postmenopausal women included in data analysis. Urine from postmenopausal women showed significantly higher alpha diversity compared to premenopausal women. Lactobacillus was the most abundant bacteria in both groups, however the relative abundance of Lactobacillus accounted for 77.8% in premenopausal versus 42.0% in postmenopausal women. In conclusion, urine from premenopausal mostly presented with Lactobacillus dominated urotypes, whereas urine from postmenopausal women presented a more diverse urinary microbiota with higher abundance of the genera Gardnerella and Prevotella. The clinical and pathophysiological implications of this difference remain to be elucidated.
Background: Duloxetine is indicated in the management of pain in osteoarthritis. Evidence suggests that duloxetine modulates central pain mechanisms and cognitive factors, and these factors are assumed contributing to the analgesic effect. This proof-of-mechanism, randomized, placebo-controlled, crossover, double-blinded trial evaluated the effect of duloxetine on quantitative sensory testing (QST), cognitive factors and clinical pain in patients with osteoarthritis and to predict the analgesic effect.Methods: Twenty-five patients completed this cross-over study with either 18week duloxetine (maximum 60 mg/daily) followed by placebo or vice-versa. Pressure pain thresholds, temporal summation of pain and conditioned pain modulation were assessed using cuff algometry. The Hospital Anxiety and Depression Scale and the Pain Catastrophizing Scale evaluated cognitive factors. Clinical pain was assessed using Brief Pain Inventory and Western Ontario andMcMaster Universities Osteoarthritis Index. Linear regression models were used to predict the analgesic effect of duloxetine.Results: Depending on the clinical pain outcome, 40%-68% of patients were classified as responders to duloxetine. Linear regression models predicted the analgesic effect (predictive value of 45%-75% depending on clinical pain outcome parameter) using a combination of pretreatment QST parameters, cognitive factors and clinical pain. No significant changes were found for QST, cognitive factors or clinical pain on a group level when comparing duloxetine to placebo.
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