Ototopical drops containing a novel antibacterial synthetic peptide: safety and efficacy in adults with chronic suppurative otitis media

ObjectiveChronic suppurative otitis media (CSOM) is a chronic infectious disease with worldwide prevalence that causes hearing loss and decreased quality of life. As current (antibiotic) treatments often unsuccessful and antibiotic resistance is emerging, alternative agents and/or strategies are urgently needed. We considered the synthetic antimicrobial and anti-biofilm peptide P60.4Ac to be an interesting candidate because it also displays anti-inflammatory activities including lipopolysaccharide-neutralizing activity. The aim of the present study was to investigate the safety and efficacy of ototopical drops containing P60.4Ac in adults with CSOM without cholesteatoma.MethodsWe conducted a range-finding study in 16 subjects followed by a randomized, double blinded, placebo-controlled, multicentre phase IIa study in 34 subjects. P60.4Ac-containing ototopical drops or placebo drops were applied twice a day for 2 weeks and adverse events (AEs) and medication use were recorded. Laboratory tests, swabs from the middle ear and throat for bacterial cultures, and audiometry were performed at intervals up to 10 weeks after therapy. Response to treatment was assessed by blinded symptom scoring on otoscopy.ResultsApplication of P60.4Ac-containing ototopical drops (0.25-2.0 mg of peptide/ml) in the ear canal of patients suffering from CSOM was found to be safe and well-tolerated. The optimal dose (0.5 mg of peptide/ml) was selected for the subsequent phase IIa study. Safety evaluation revealed only a few AEs that were unlikely related to study treatment and all, except one, were of mild to moderate intensity. In addition to this excellent safety profile, P60.4Ac ototopical drops resulted in a treatment success in 47% of cases versus 6% in the placebo group.ConclusionThe efficacy/safety balance assessed in the present study provides a compelling justification for continued clinical development of P60.4Ac in therapy-resistant CSOM.Development and application of statistical models for medical scientific researc

The relationship between body mass index and sleep in women with risk factors for gestational diabetes mellitus

OnlinePublBackground: Both obesity and sleep disorders are common among women during pregnancy. Although prior research has identified a relationship between obesity and sleep disorders, those findings are from women later in pregnancy. Objective: To explore the relationships between self‐reported sleep duration, insufficient sleep and snoring with body mass index (BMI) among multiethnic women at risk of gestational diabetes mellitus (GDM)in early pregnancy.Methods: Cross‐sectional study of baseline data from women at risk of GDM enrolled in the Treatment of BOoking Gestational diabetes Mellitus (TOBOGM) multicentre trial across 12 Australian/Austrian sites. Participants completed a questionnaire before 20 weeks’ gestation to evaluate sleep. BMI 5 days/ month was higher in class II and class III obesity (1.38 (1.03–1.85) and 1.34 (1.01– 1.80), respectively), and the risk of snoring increased as BMI increased (1.59 (1.25– 2.02), 2.68 (2.07–3.48), 4.35 (3.21–5.88) to 4.96 (3.65–6.74), respectively)). Conclusions: Obesity is associated with insufficient sleep among pregnant women at risk of GDM. Snoring is more prevalent with increasing BMI.Pamela Acosta Reyes, Jincy Immanuel, William M. Hague, Helena Teede, Emily Hibbert, Christopher J. Nolan, Michael J. Peek, Vincent Wong, Jeffrey R. Flack, Mark McLean, Raiyomand Dalal, Jürgen Harreiter, Alexandra Kautzky, Willer, Rohit Rajagopal, Arianne Sweeting, Glynis P. Ross, Ngai Wah Cheung, David Simmon

Expression of angiogenic and immunosuppressive factors by uveal melanoma cell lines.

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Ovarian follicles of young patients with Turner's syndrome contain normal oocytes but monosomic 45,X granulosa cells

Contains fulltext : 208683.pdf (publisher's version ) (Open Access)STUDY QUESTION: What is the X chromosomal content of oocytes and granulosa cells of primordial/primary (small) follicles and stromal cells in ovaries of young patients with Turner's syndrome (TS)? SUMMARY ANSWER: Small ovarian follicles were detected in one-half of the patients studied, and X chromosome analysis revealed that most oocytes were normal, granulosa cells were largely monosomic, while stromal cells showed a high level of mosaicism. WHAT IS KNOWN ALREADY: Most women with TS experience a premature reduction or complete loss of fertility due to an accelerated loss of gametes. To determine whether fertility preservation in this group of patients is feasible, there is a strong need for information on the X chromosomal content of ovarian follicular and stromal cells. STUDY DESIGN, SIZE, DURATION: Small follicles (<50 mum) and stromal cells were isolated from ovarian tissue of young TS patients and analysed for their X chromosomal content. In addition to ovarian cells, several other cell types from the same patients were analysed. PARTICIPANTS/MATERIALS, SETTING, METHODS: After unilateral ovariectomy, ovarian cortex tissue was obtained from 10 TS patients (aged 2-18 years) with numerical abnormalities of the X chromosome. Ovarian cortex fragments were prepared and cryopreserved. One fragment from each patient was thawed and enzymatically digested to obtain stromal cells and primordial/primary follicles. Stromal cells, granulosa cells and oocytes were analysed by FISH using an X chromosome-specific probe. Extra-ovarian cells (lymphocytes, buccal cells and urine cells) of the same patients were also analysed by FISH. Ovarian tissue used as control was obtained from individuals undergoing oophorectomy as part of their gender affirming surgery. MAIN RESULTS AND THE ROLE OF CHANCE: Ovarian follicles were detected in 5 of the 10 patients studied. A method was developed to determine the X chromosomal content of meiosis I arrested oocytes from small follicles. This revealed that 42 of the 46 oocytes (91%) that were analysed had a normal X chromosomal content. Granulosa cells were largely 45,X but showed different levels of X chromosome mosaicism between patients and between follicles of the same patient. Despite the presence of a low percentage (10-45%) of 46,XX ovarian cortex stromal cells, normal macroscopic ovarian morphology was observed. The level of mosaicism in lymphocytes, buccal cells or urine-derived cells was not predictive for mosaicism in ovarian cells. LIMITATIONS, REASONS FOR CAUTION: The results are based on a small number (n = 5) of TS patient samples but provide evidence that the majority of oocytes have a normal X chromosomal content and that follicles from the same patient can differ with respect to the level of mosaicism of their granulosa cells. The functional consequences of these observations require further investigation. WIDER IMPLICATIONS OF THE FINDINGS: The results indicate that despite normal ovarian and follicular morphology, stromal cells and granulosa cells of small follicles in patients with TS may display a high level of mosaicism. Furthermore, the level of mosaicism in ovarian cells cannot be predicted from the analysis of extra-ovarian tissue. These findings should be considered by physicians when offering cryopreservation of ovarian tissue as an option for fertility preservation in young TS patients. STUDY FUNDING/COMPETING INTEREST(S): Unconditional funding was received from Merck B.V. The Netherlands (Number A16-1395) and the foundation 'Radboud Oncologie Fonds' (Number KUN 00007682). The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: NCT03381300

To Freeze or Not to Freeze? An Update on Fertility Preservation In Females with Turner Syndrome

Introduction Infertility is a major concern for females with Turner syndrome (TS), regardless of their age. While fertility preservation is now routinely offered to girls and young women with cancer, there are currently no recommendations on fertility preservation in girls and young women with TS who generally face an even higher risk for infertility. Despite the lack of international guidelines, preservation procedures have been performed experimentally in females with TS. Methods A systematic literature search based on the PRISMA-P methodology for systematic reviews was performed in order to collect all published data on fertility preservation options in females with TS between January 1980 and April 2018. A total number of 67 records were included in this review. The records were screened for information regarding cryopreservation of mature oocytes and ovarian tissue in females with TS. Two ongoing trials on fertility preservation in young females with TS were also included. Results Cryopreservation of oocytes or ovarian tissue has been performed experimentally in >150 girls and adolescents with TS over the last 16 years. The efficacy of fertility preservation options in females with TS is still unknown due to the lack of follow-up data. Conclusion The efficacy of fertility preservation procedures in females with TS is still unknown. Future studies with focus on efficacy, safety and long-term follow-up are desperately needed