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Catalysis is an important process across multiple disciplines, and there are still many challenges to be met. Enzymes, “nature’s catalysts”, display impressive efficacy with controlled selectivity and rapid throughput, so attempting to mimic these properties opens up exciting pathways in catalyst research. In recent years, metallo-organic coordination cages have shown promise in exploring these avenues. Their unique structures and modifiable properties present opportunities not available to traditional catalysts. This mini-review provides a general introduction to the field, then attempts to extract effects ascribed to interior versus surface or exterior influences, illustrating these with recently published results.

Background/Objectives: Cow’s milk is a complex food, and research into its metabolome can provide information useful in the study of animal health, farming practices, food safety and the adulteration of milk. Comparative interlaboratory metabolic analysis is hampered by the lack of standardized methods—a requirement addressed in this study. Methods: We studied the influence of the chromatography column and extraction solvent on the metabolites isolated during untargeted metabolomics. Results: After studying fifteen columns and four extraction solvents, it was determined that an HILIC column offered the best compromise between retention time and separation of metabolites. Each extraction solvent covered a different area of the metabolome, only overlapping with previously annotated compounds. Extraction mixtures containing methanol tend to give better recovery. Conclusions: The choice of extraction solvent was crucial when looking at the difference between samples, but if interest lies only in previously annotated compounds, then there is little difference between the solvents.

Substituted [2.2]metaparacyclophanes are amongst the least studied of the simple cyclophanes. This is undoubtedly the result of the lengthy syntheses of these compounds. We report the simple synthesis of a rare example of a non-symmetric [2.2]metaparacyclophane. Treatment of [2.2]paracyclophane under standard nitration conditions gives a mixture of 4-nitro[2.2]paracyclophane, 4-hydroxy-5-nitro[2.2]metaparacyclophane and a cyclohexadienone cyclophane.

Synergistic antibiotic combinations are a promising alternative strategy for developing effective therapies for multidrug-resistant bacterial infections. The synergistic combination of the existing antibiotics nitrofurans and vancomycin with sodium deoxycholate shows promise in inhibiting and killing multidrug-resistant Gram-negative bacteria. Effective therapeutic options are urgently needed to tackle antibiotic resistance. Furazolidone (FZ), vancomycin (VAN), and sodium deoxycholate (DOC) show promise as their combination can synergistically inhibit the growth of, and kill, multidrug-resistant Gram-negative bacteria that are classified as critical priority by the World Health Organization. Here, we investigated the mechanisms of action and synergy of this drug combination using a transcriptomics approach in the model bacterium Escherichia coli . We show that FZ and DOC elicit highly similar gene perturbations indicative of iron starvation, decreased respiration and metabolism, and translational stress. In contrast, VAN induced envelope stress responses, in agreement with its known role in peptidoglycan synthesis inhibition. FZ induces the SOS response consistent with its DNA-damaging effects, but we demonstrate that using FZ in combination with the other two compounds enables lower dosages and largely mitigates its mutagenic effects. Based on the gene expression changes identified, we propose a synergy mechanism where the combined effects of FZ, VAN, and DOC amplify damage to Gram-negative bacteria while simultaneously suppressing antibiotic resistance mechanisms. IMPORTANCE Synergistic antibiotic combinations are a promising alternative strategy for developing effective therapies for multidrug-resistant bacterial infections. The synergistic combination of the existing antibiotics nitrofurans and vancomycin with sodium deoxycholate shows promise in inhibiting and killing multidrug-resistant Gram-negative bacteria. We examined the mechanism of action and synergy of these three antibacterials and proposed a mechanistic basis for their synergy. Our results highlight much-needed mechanistic information necessary to advance this combination as a potential therapy.

AbstractWe report an improved method to make the ligand N,N′-(pyrazine-2,5-diylbis(methanylylidene))bis(2-(pyridin-2-yl)ethanamine) (L) and the subsequent complexation of this ligand to make the triangular metallo-macrocycles [Co3L3](ClO4)6·2H2O (C1·2H2O) and [Mn3L3](ClO4)6·3H2O (C2·3H2O). Single crystal X-ray analysis of both trimeric circular helicates reveal the complexes pack in enantiomeric pairs in close synergy with the accompanying anions.Graphical abstract

BackgroundRisk-reducing salpingo-oophorectomy is the 'gold standard' for preventing tubo-ovarian cancer in women at increased risk. However, when performed in pre-menopausal women, it results in premature menopause and associated detrimental health consequences. This, together with acceptance of the central role of the fallopian tube in etiopathogenesis of high-grade serous carcinoma, by far the most common type of tubo-ovarian cancer, has led to risk-reducing early salpingectomy with delayed oophorectomy being proposed as a two-step surgical alternative for pre-menopausal women declining/delaying oophorectomy.Primary ObjectiveTo evaluate the impact on sexual function of risk-reducing early salpingectomy, within a two-step, risk-reducing, early salpingectomy with delayed oophorectomy tubo-ovarian cancer prevention strategy in pre-menopausal women at increased risk of tubo-ovarian cancer.Study HypothesisRisk-reducing early salpingectomy is non-inferior for sexual and endocrine function compared with controls; risk-reducing early salpingectomy is superior for sexual/endocrine function, non-inferior for quality-of-life, and equivalent in satisfaction to the standard risk-reducing salpingo-oophorectomy.Trial DesignMulti-center, observational cohort trial with three arms: risk-reducing early salpingectomy with delayed oophorectomy; risk-reducing salpingo-oophorectomy; controls (no surgery). Consenting individuals undergo an ultrasound, serum CA125, and follicle-stimulating hormone measurements and provide information on medical history, family history, quality-of-life, sexual function, cancer worry, psychological well-being, and satisfaction/regret. Follow-up by questionnaire takes place annually for 3 years. Women receiving risk-reducing early salpingectomy can undergo delayed oophorectomy at a later date of their choosing, or definitely by the menopause.Major Inclusion/Exclusion CriteriaInclusion criteria: pre-menopausal; aged >30 years; at increased risk of tubo-ovarian cancer (mutation carriers or on the basis of a strong family history); completed their family (for surgical arms). Exclusion criteria: post-menopausal; previous bilateral salpingectomy or bilateral oophorectomy; pregnancy; previous tubal/ovarian/peritoneal malignancy; <12 months after cancer treatment; clinical suspicion of tubal/ovarian cancer at baseline.Primary EndpointSexual function measured by validated questionnaires.Sample Size1000 (333 per arm).Estimated Dates for Completing Accrual and Presenting ResultsIt is estimated recruitment will be completed by 2023 and results published by 2027.Trial Registration NumberISRCTN registry: 25 173 360 (https://doi.org/10.1186/ISRCTN25173360).

BackgroundAcceptance of the role of the fallopian tube in ‘ovarian’ carcinogenesis and the detrimental sequelae of surgical menopause in premenopausal women following risk-reducing salpingo-oophorectomy (RRSO) has resulted in risk-reducing early-salpingectomy with delayed oophorectomy (RRESDO) being proposed as an attractive alternative risk-reducing strategy in women who decline/delay oophorectomy. We present the results of a qualitative study evaluating the decision-making process among BRCA carriers considering prophylactic surgeries (RRSO/RRESDO) as part of the multicentre PROTECTOR trial (ISRCTN:25173360).MethodsIn-depth semistructured 1:1 interviews conducted using a predeveloped topic-guide (development informed by literature review and expert consultation) until informational saturation reached. Wording and sequencing of questions were left open with probes used to elicit additional information. All interviews were audio-recorded, transcribed verbatim, transcripts analysed using an inductive theoretical framework and data managed using NVIVO-v12.ResultsInformational saturation was reached following 24 interviews. Seven interconnected themes integral to surgical decision making were identified: fertility/menopause/cancer risk reduction/surgical choices/surgical complications/sequence of ovarian-and-breast prophylactic surgeries/support/satisfaction. Women for whom maximising ovarian cancer risk reduction was relatively more important than early menopause/quality-of-life preferred RRSO, whereas those more concerned about detrimental impact of menopause chose RRESDO. Women managed in specialist familial cancer clinic settings compared with non-specialist settings felt they received better quality care, improved hormone replacement therapy access and were more satisfied.ConclusionMultiple contextual factors (medical, physical, psychological, social) influence timing of risk-reducing surgeries. RRESDO offers women delaying/declining premenopausal oophorectomy, particularly those concerned about menopausal effects, a degree of ovarian cancer risk reduction while avoiding early menopause. Care of high-risk women should be centralised to centres with specialist familial gynaecological cancer risk management services to provide a better-quality, streamlined, holistic multidisciplinary approach.

Introduction/BackgroundPROTECTOR (ISRCTN25173360) evaluates outcomes of pre-menopausal women at increased ovarian cancer(OC) risk, who choose risk-reducing early-salpingectomy (RRES) and delayed-oophorectomy (DO), salpingo-oophorectomy (RRSO), or no surgery. No qualitative study has explored quality-of-life and satisfaction after RRESDO. This study aims to explore satisfaction, experiences and outcomes of risk-reducing surgery on health and wellbeing.MethodologyQualitative sub-study within PROTECTOR. We conducted in-depth semi-structured 1:1 telephone interviews after RRES/DO/RRSO, until sufficient information power reached. All interviews were audio-recorded, transcribed, and analysed using applied thematic analysis. Data was managed using NVIVO-v12.ResultsWe interviewed 28 participants following surgery: 8 RRSO, 10 RRES, 10 DO, including 4 with serous tubal intraepithelial carcinoma (STIC) and 2 with incidental OC on histology. Median age was 42 years, and median follow-up 32 months. 6 themes were interpreted: 1) Impact of initial decision-making, 2) Menopause, 3) Cancer worry, 4) Considerations between RRES and DO, 5) Attitudes to fertility, 6) Health outlook. There was high satisfaction and low decision-regret after risk-reducing surgery. Participants greatly valued the option of RRESDO, this enabled earlier access to risk-reducing surgery for some, and those with STIC/OC were especially grateful for their initial surgery, feeling that RRES saved their life. Patients with STIC have cancer worry and concerns which are not currently addressed. The decision for DO is more complex than RRES, influenced by cancer worry and menopause issues, and regular follow-up is valued. There was huge variation in counselling and treatment of menopause, which greatly affected quality-of-life.ConclusionThis study provides valuable insights not previously reported after RRESDO and STIC, which have service implications. Participants are highly satisfied with their decision for risk-reducing surgery, however after RRES they value regular follow-up to enable planning of DO. Participants strongly prefer specialist advice and management of menopause. Those diagnosed with STIC experience increased cancer worry and desire further follow-up.DisclosuresThe PROTECTOR trial is supported by the Rosetrees Trust and Barts Charity.

Introduction/BackgroundBorderline ovarian tumours (BOT) are low malignant potential tumours. There is no consensus on how best to follow up those patients. The aim of this service evaluation project is to assess our current management and long-term outcomes and follow up in women diagnosed with borderline ovarian tumours over a ten-year period.MethodologyAll women with confirmed histological diagnosis of BOT who underwent primary surgery at SEWGOC between 1st January 2007 to 31st December 2016 were included. Retrospective review of patients’ electronic medical records was undertaken. Information regarding FIGO stages, management (fertility preserving surgery/pelvic clearance), follow up and recurrence were analysed.ResultsSeventy-nine patients were diagnosed with BOT. The mean age was 48 years (range 18 – 86). Of these, 67 were stage I, 4 stage II and 8 stage III. Fertility sparing surgery (mean age 38) was performed in 32 patients (30 stage I, 2 stage III). Of these, 22 had follow-up. Four of 32 (12.5%) had recurrences. Pelvic clearance (mean age 55) was undertaken in 47 patients. Of these, 23 had follow up. Three of 47 (6%) patients presented with recurrence. All recurred within 5 years.ConclusionThis evaluation shows that recurrence in women who undergo fertility sparing surgery is doubled versus pelvic clearance. All patients with recurrence presented with symptoms within 5 years of initial surgery. Symptom-led follow up could be a suitable modality especially in those who underwent pelvic clearance.

Substituted [2.2]metaparacyclophanes are amongst the least studied of the simple cyclophanes. This is undoubtedly the result of the lengthy syntheses of these compounds. We report the simple synthesis of a rare example of a non-symmetric [2.2]metaparacyclophane. Treatment of [2.2]paracyclophane under standard nitration conditions gives a mixture of 4-nitro[2.2]paracyclophane, 4-hydroxy-5-nitro[2.2]metaparacyclophane and a cyclohexadienone cyclophane.Substituted [2.2]metaparacyclophanes are amongst the least studied of the simple cyclophanes. This is undoubtedly the result of the lengthy syntheses of these compounds. We report the simple synthesis of a rare example of a non-symmetric [2.2]metaparacyclophane. Treatment of [2.2]paracyclophane under standard nitration conditions gives a mixture of 4-nitro[2.2]paracyclophane, 4-hydroxy-5-nitro[2.2]metaparacyclophane and a cyclohexadienone cyclophane.