Probing the action of a novel anti-leukaemic drug therapy at the single cell level using modern vibrational spectroscopy techniques

Acute myeloid leukaemia (AML) is a life threatening cancer for which there is an urgent clinical need for novel therapeutic approaches. A redeployed drug combination of bezafibrate and medroxyprogesterone acetate (BaP) has shown anti-leukaemic activity in vitro and in vivo. Elucidation of the BaP mechanism of action is required in order to understand how to maximise the clinical benefit. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, Synchrotron radiation FTIR (S-FTIR) and Raman microspectroscopy are powerful complementary techniques which were employed to probe the biochemical composition of two AML cell lines in the presence and absence of BaP. Analysis was performed on single living cells along with dehydrated and fixed cells to provide a large and detailed data set. A consideration of the main spectral differences in conjunction with multivariate statistical analysis reveals a significant change to the cellular lipid composition with drug treatment; furthermore, this response is not caused by cell apoptosis. No change to the DNA of either cell line was observed suggesting this combination therapy primarily targets lipid biosynthesis or effects bioactive lipids that activate specific signalling pathways

Influence of maternal obesity on Bishop Score and failed induction of labour: a retrospective cohort study in a regional tertiary centre

Background: Maternal obesity is a growing health concern that has previously been associated with increased need for induction of labour (IOL) and caesarean section (CS) rates. Currently, limited evidence explores the influence of maternal body mass index (BMI) on Bishop Score (BS) and outcome of IOL. This study hypothesises that maternal obesity will lead to a lower BS at presentation, higher rates of failed IOL, and increased CS rates. Aims: To explore the influence of maternal obesity on BS and likelihood of failed IOL. Methods: A retrospective cohort analysis was conducted of all live, term, singleton, cephalic deliveries initiated with IOL across normal BMI (18.00–24.99), overweight BMI (25.00–29.99), and obese BMI (>30.00) at the Townsville Hospital and Health Service (THHS) between July 2011 to June 2016. Student’s t‐test, χ2 test, and binary logistic regression were used for statistical analysis. BS and failed IOL, defined as CS with cervical dilatation <3 cm, were the primary outcome measures. Delivery mode was the secondary outcome measure. Results: A total of 1543 women were included, 678 with normal BMI, 370 with overweight BMI, and 495 with obese BMI. Obese women are more likely to have a low BS (<5) at presentation (unadjusted odds ratio (OR) 1.5 (1.1–2.0), P < 0.05), an increased rate of failed IOL (adjusted OR (aOR) 1.6 (1.0–2.5), P < 0.05) and increased CS rate (aOR 1.1 (1.0–1.9), P < 0.05), compared to normal weight women. Conclusions: Maternal obesity is associated with a lower BS, more difficult IOL process, and increased risk of failed IOL and CS