eous activity but remain healthy brain functional networks.
  The main objective of this open, prospective, multicentre, observational study is to investigate the relapse rate and tolerability of lactic acid gels in adult female patients with recurrent urinary tract infections during routine practice.
 
  Data were collected from patients undergoing intermittent short courses of intravaginal treatment with lactic acid gel for prevention of recurrent urinary tract infections. The observation period for individual patients was 4 months, aimed at covering four short courses of intravaginal treatment. Data on UTI relapses, tolerability, handling and satisfaction with the treatment were collected via patient diaries and physician assessments and comprised any adverse events (AEs).
 
  In total, 72 patients were treated. During the last 12months prior to the study, patients had on average 4.0 UTIs. In the 4months after commencing treatment, 63.5% of patients had no recurrence of UTI symptoms. Overall efficacy was rated by physicians as 'excellent/good' for 96.7% of patients. The patients' overall acceptance of local treatment was high with 94.1% being '(very) satisfied'. Similarly, handling was rated as '(very) easy' by 94.2% of patients. The tolerability was assessed as 'highly tolerable/tolerable' by over 98% of patients and physicians alike. Safety analyses reported six AEs of mild intensity, all of which had resolved by the end of the study.
 
  Treatment with lactic acid gel may increase resilience against uropathogens, possibly preventing the need for antibiotic prevention of recurrent urinary tract infections. Treatment was positively assessed by the patients. The physician assessments corroborate these findings.
 
  DRKS00016760, 18.02.2019.
 DRKS00016760, 18.02.2019.
  The present study aimed to explore the associations between the expression pattern of molecules in the Notch pathway in the cumulus cells of polycystic ovary syndrome (PCOS) patients and the quality of zygotes and embryos.
 
  A total of 200 cumulus complexes surrounding mature oocytes were obtained from 40 patients with and without PCOS undergoing intracytoplasmic sperm injection (ICSI). The expressions of Notch-1, Notch-2, and Notch-3 genes were examined by Reverse Transcription Q-PCR assay. Moreover, immunocytochemistry was performed for the expressions of Jagged-1 and Jagged-2 proteins. The correlations between the Notch receptors and their ligand expressions and the qualities of the zygote and embryo were investigated.
 
  The expression levels of Notch-2, Notch-3, Jagged-1, and Jagged-2 were significantly lower in patients with PCOS than in normal women (p < 0.05), while Notch-1 showed no meaningful difference between the groups. A positive correlation was found between Notch-1 and embryo quality. Furthermore, only Notch-2 and Jagged-2 marginally correlated with zygote quality.
 
  The data of the present study indicated that evaluating the molecules in the Notch pathway in PCOS patients' cumulus cells provides a novel approach to predict the zygote and embryo quality. However, further studies on a larger population are needed to validate this finding.
 The data of the present study indicated that evaluating the molecules in the Notch pathway in PCOS patients' cumulus cells provides a novel approach to predict the zygote and embryo quality. However, further studies on a larger population are needed to validate this finding.This study assessed the cost effectiveness of romosozumab versus teriparatide, both sequenced to alendronate, for the treatment of severe postmenopausal osteoporosis in Japan, using bone mineral density (BMD) efficacy data. Results show that romosozumab/alendronate produces greater health benefits at a lower cost than teriparatide/alendronate.
  This study aims to assess the cost effectiveness of romosozumab versus teriparatide, both sequenced to alendronate, for the treatment of severe postmenopausal osteoporosis in Japanese women previously treated with bisphosphonates.
 
  A Markov model was used to assess the relative cost effectiveness of 1 year of romosozumab versus 2 years of teriparatide, both sequenced to alendronate for a total treatment duration of 5 years. Outcomes for a cohort of women with a mean age of 78 years, a T-score ≤-2.5 and a previous fragility fracture were simulated over a lifetime horizon. The analysis was conducted from the perspective of the Japanese healthcare system and used a discount rate of 2% per annum. To inform relative fracture incidence, the bone mineral density (BMD) advantage of romosozumab over teriparatide was translated into relative risks of fracture, using relationships provided by a meta-regression of osteoporosis therapy trials. Outcomes were assessed in terms of lifetime costs (2020 US dollars) and quality-adjusted life years (QALYs).
 
  Base case results showed that, compared with teriparatide/alendronate, romosozumab/alendronate reduced costs by $5134 per patient and yielded 0.045 additional QALYs. Scenario analyses and probabilistic sensitivity analysis confirmed that results are robust to uncertainty in model assumptions and inputs.
 
  Results show that romosozumab/alendronate produces greater health benefits at a lower total cost than teriparatide/alendronate.
 Results show that romosozumab/alendronate produces greater health benefits at a lower total cost than teriparatide/alendronate.Denosumab has been advocated as a potential treatment for the rare skeletal disorder fibrous dysplasia (FD); however, there is limited data to support safety and efficacy, particularly after drug discontinuation. We report a case of successful treatment of aggressive craniofacial FD with denosumab, highlighting novel insights into the duration of efficacy, surrogate treatment markers, and discontinuation effects. A 13-year-old girl presented with persistent pain and expansion of a maxillary FD lesion, which was not responsive to repeated surgical procedures or bisphosphonates. Pre-treatment biopsy showed high RANKL expression and localization with proliferation markers. Denosumab therapy was associated with improved pain, decreased bone turnover markers, and increased lesion density on computed tomography scan. During 3.5 years of treatment, the patient developed increased non-lesional bone density, and after denosumab discontinuation, she developed hypercalcemia managed with bisphosphonates.  https://www.selleckchem.com/products/liraglutide.html  Pain relief and lesion stability continued for 2 years following treatment, and symptom recurrence coincided with increased bone turnover markers and decreased lesion density back to pre-treatment levels.