Anticancer activities of fatty acids and their heterocyclic derivatives

Traditional chemotherapy relies on the premise that rapidly proliferating cancer cells are more likely to be killed by a cytotoxic agent, but in reality, the long-standing problem of chemotherapy is the lack of tumor-specific treatments. Apart from the impact on tumor cells, the drugs’ major limitation is their severe adverse side effects on normal cells and tissues. Nutritional and epidemiological studies have indicated that cancer progression is correlated with the consumption of fatty acids, but the exact mechanisms still remain unknown. In the first part of our review, we discussed the beneficial effects of free fatty acids (saturated and unsaturated) on the progress of carcinogenesis in different tumor cell lines. We presented various mechanisms proposed in the literature, which explain the possible impact on the cells metabolism. The second part describes modifications of different fatty acids with existing anticancer drugs and heterocyclic moieties by condensation reactions. Such conjugations increased the tissue selectivity and made chemotherapy potentially more effective and less toxic in in vivo and in vitro studies. This fatty acid modifications, which change the activity of compounds, their uptake selectivity and alter drug delivery methods, may be the key to unlocking true medical potential of fatty acids

Methods of term labour induction for women with a previous caesarean section

Background: Women with a prior caesarean delivery have an increased risk of uterine rupture and for women subsequently requiring induction of labour it is unclear which method is preferable to avoid adverse outcomes. This is an update of a review that was published in 2013. Objectives: To assess the benefits and harms associated with different methods used to induce labour in women who have had a previous caesarean birth. Search methods: We searched Cochrane Pregnancy and Childbirth's Trials Register (31 August 2016) and reference lists of retrieved studies. Selection criteria: Randomised controlled trials (RCTs) comparing any method of third trimester cervical ripening or labour induction, with placebo/no treatment or other methods in women with prior caesarean section requiring labour induction in a subsequent pregnancy. Data collection and analysis: Two review authors independently assessed studies for inclusion and trial quality, extracted data, and checked them for accuracy. Main results: Eight studies (data from 707 women and babies) are included in this updated review. Meta-analysis was not possible because studies compared different methods of labour induction. All included studies had at least one design limitation (i.e. lack of blinding, sample attrition, other bias, or reporting bias). One study stopped prematurely due to safety concerns. Vaginal PGE2 versus intravenous oxytocin: (one trial, 42 women): no clear differences for caesarean section (risk ratio (RR) 0.67, 95% confidence interval (CI) 0.22 to 2.03, evidence graded low), serious neonatal morbidity or perinatal death (RR 3.00, 95% CI 0.13 to 69.70, evidence graded low), serious maternal morbidity or death (RR 3.00, 95% CI 0.13 to 69.70, evidence graded low). Also no clear differences between groups for the reported secondary outcomes. The GRADE outcomes vaginal delivery not achieved within 24 hours, and uterine hyperstimulation with fetal heart rate changes were not reported. Vaginal misoprostol versus intravenous oxytocin (one trial, 38 women): this trial stopped early because one woman who received misoprostol had a uterine rupture (RR 3.67, 95% CI 0.16 to 84.66) and one had uterine dehiscence. No other outcomes (including GRADE outcomes) were reported. Foley catheter versus intravenous oxytocin (one trial, subgroup of 53 women): no clear difference between groups for vaginal delivery not achieved within 24 hours (RR 1.47, 95% CI 0.89 to 2.44, evidence graded low), uterine hyperstimulation with fetal heart rate changes (RR 3.11, 95% CI 0.13 to 73.09, evidence graded low), and caesarean section (RR 0.93, 95% CI 0.45 to 1.92, evidence graded low). There were also no clear differences between groups for the reported secondary outcomes. The following GRADE outcomes were not reported: serious neonatal morbidity or perinatal death, and serious maternal morbidity or death. Double-balloon catheter versus vaginal PGE2 (one trial, subgroup of 26 women): no clear difference in caesarean section (RR 0.97, 95% CI 0.41 to 2.32, evidence graded very low). Vaginal delivery not achieved within 24 hours, uterine hyperstimulation with fetal heart rate changes, serious neonatal morbidity or perinatal death, and serious maternal morbidity or death were not reported. Oral mifepristone versus Foley catheter (one trial, 107 women): no primary/GRADE outcomes were reported. Fewer women induced with mifepristone required oxytocin augmentation (RR 0.54, 95% CI 0.38 to 0.76). There were slightly fewer cases of uterine rupture among women who received mifepristone, however this was not a clear difference between groups (RR 0.29, 95% CI 0.08 to 1.02). No other secondary outcomes were reported. Vaginal isosorbide mononitrate (IMN) versus Foley catheter (one trial, 80 women): fewer women induced with IMN achieved a vaginal delivery within 24 hours (RR 2.62, 95% CI 1.32 to 5.21, evidence graded low). There was no difference between groups in the number of women who had a caesarean section (RR 1.00, 95% CI 0.39 to 2.59, evidence graded very low). More women induced with IMN required oxytocin augmentation (RR 1.65, 95% CI 1.17 to 2.32). There were no clear differences in the other reported secondary outcomes. The following GRADE outcomes were not reported: uterine hyperstimulation with fetal heart rate changes, serious neonatal morbidity or perinatal death, and serious maternal morbidity or death. 80 mL versus 30 mL Foley catheter (one trial, 154 women): no clear difference between groups for the primary outcomes: vaginal delivery not achieved within 24 hours (RR 1.05, 95% CI 0.91 to 1.20, evidence graded moderate) and caesarean section (RR 1.05, 95% CI 0.89 to 1.24, evidence graded moderate). However, more women induced using a 30 mL Foley catheter required oxytocin augmentation (RR 0.81, 95% CI 0.66 to 0.98). There were no clear differences between groups for other secondary outcomes reported. Several GRADE outcomes were not reported: uterine hyperstimulation with fetal heart rate changes, serious neonatal morbidity or perinatal death, and serious maternal morbidity or death. Vaginal PGE2 pessary versus vaginal PGE2 tablet (one trial, 200 women): no difference between groups for caesarean section (RR 1.09, 95% CI 0.74 to 1.60, evidence graded very low), or any of the reported secondary outcomes. Several GRADE outcomes were not reported: vaginal delivery not achieved within 24 hours, uterine hyperstimulation with fetal heart rate changes, serious neonatal morbidity or perinatal death, and serious maternal morbidity or death.RCT evidence on methods of induction of labour for women with a prior caesarean section is inadequate, and studies are underpowered to detect clinically relevant differences for many outcomes. Several studies reported few of our prespecified outcomes and reporting of infant outcomes was especially scarce. The GRADE level for quality of evidence was moderate to very low, due to imprecision and study design limitations.High-quality, adequately-powered RCTs would be the best approach to determine the optimal method for induction of labour in women with a prior caesarean birth. However, such trials are unlikely to be undertaken due to the very large numbers needed to investigate the risk of infrequent but serious adverse outcomes (e.g. uterine rupture). Observational studies (cohort studies), including different methods of cervical ripening, may be the best alternative. Studies could compare methods believed to provide effective induction of labour with low risk of serious harm, and report the outcomes listed in this review.Helen M West, Marta Jozwiak, Jodie M Dod

Induction of labour : Foley catheter revisited

In the 1980s prostaglandin analogues were introduced for induction of labour without good evidence of superiority over older methods, such as Foley catheter. The aim of this thesis was to investigate the use of Foley catheter as an induction agent in women with an unfavourable cervix at term, compared to prostaglandins. The studies in this thesis demonstrate that Foley catheter yields similar caesarean sectio rates compared to vaginally administered prostaglandins, making both methods equally effective. Findings from RCTs and meta-analysis in this dissertation show reduced side effects with Foley catheter. Costs are comparable, and could further be reduced in favour of Foley catheter when used in an outpatient setting. This makes Foley catheter a superior method, with potential for outpatient cervical ripening, cervical ripening in low-resource settings, and cervical ripening in women with prior caesarean birth.UBL - phd migration 201

Bond stretching phonon softening and angle-resolved photoemission kinks in optimally doped Bi2Sr1.6La0.4Cu2O6 superconductors

We report the first measurement of the optical phonon dispersion in optimally doped single layer Bi2Sr1.6La0.4Cu2O6+delta using inelastic x-ray scattering. We found a strong softening of the Cu-O bond stretching phonon at about q=(0.25,0,0) from 76 to 60 meV, similar to the one reported in other cuprates. A direct comparison with angle-resolved photoemission spectroscopy measurements taken on the same sample, revealed an excellent agreement in terms of energy and momentum between the ARPES nodal kink and the soft part of the bond stretching phonon. Indeed, we find that the momentum space where a 63 meV kink is observed can be connected with a vector q=(xi,0,0) with xi~0.22, which corresponds exactly to the soft part of the bond stretching phonon mode. This result supports an interpretation of the ARPES kink in terms of electron-phonon coupling.Comment: submited to PR

Evidence for Weyl fermions in a canonical heavy-fermion semimetal YbPtBi

The manifestation of Weyl fermions in strongly correlated electron systems is of particular interest. We report evidence for Weyl fermions in the heavy fermion semimetal YbPtBi from electronic structure calculations, angle-resolved photoemission spectroscopy, magnetotransport and calorimetric measurements. At elevated temperatures where $4f$-electrons are localized, there are triply degenerate points, yielding Weyl nodes in applied magnetic fields. These are revealed by a contribution from the chiral anomaly in the magnetotransport, which at low temperatures becomes negligible due to the influence of electronic correlations. Instead, Weyl fermions are inferred from the topological Hall effect, which provides evidence for a Berry curvature, and a cubic temperature dependence of the specific heat, as expected from the linear dispersion near the Weyl nodes. The results suggest that YbPtBi is a Weyl heavy fermion semimetal, where the Kondo interaction renormalizes the bands hosting Weyl points. These findings open up an opportunity to explore the interplay between topology and strong electronic correlations.Comment: 19 pages, 5 figures, Supplementary Information available with open access at https://www.nature.com/articles/s41467-018-06782-