Apoptosis has been considered the main mechanism induced by cancer chemotherapeutic drugs for a long time. This paradigm is currently evolving and changing, as increasing evidence pointed out that ...antitumor agents could trigger various non-canonical or non-apoptotic cell death types. A considerable number of antitumor drugs derive from natural sources, both in their naturally occurring form or as synthetic derivatives. Therefore, it is not surprising that several natural compounds have been explored for their ability to induce non-canonical cell death. The aim of this review is to highlight the potential antitumor effects of natural products as ferroptosis, necroptosis, or pyroptosis inducers. Natural products have proven to be promising non-canonical cell death inducers, capable of overcoming cancer cells resistance to apoptosis. However, as discussed in this review, they often lack a full characterization of their antitumor activity together with an in-depth investigation of their toxicological profile.
The marine ecosystem, populated by a myriad of animals, plants, and microorganisms, is an inexhaustible reservoir of pharmacologically active molecules. Among the multiple secondary metabolites ...produced by marine sources, there are anthraquinones and their derivatives. Besides being mainly known to be produced by terrestrial species, even marine organisms and the uncountable kingdom of marine microorganisms biosynthesize anthraquinones. Anthraquinones possess many different biological activities, including a remarkable antitumor activity. However, due to their peculiar chemical structures, anthraquinones are often associated with toxicological issues, even relevant, such as genotoxicity and mutagenicity. The aim of this review is to critically describe the anticancer potential of anthraquinones derived from marine sources and their genotoxic and mutagenic potential. Marine-derived anthraquinones show a promising anticancer potential, although clinical studies are missing. Additionally, an in-depth investigation of their toxicological profile is needed before advocating anthraquinones as a therapeutic armamentarium in the oncological area.
Despite widespread implementation across Africa, there is limited evidence of the effect of payment for performance (P4P) schemes in low income countries on the coverage of quality services and ...affordability, consistent with universal health coverage objectives. We examined the effect of a government P4P scheme on utilisation, quality, and user costs of health services in Tanzania.
We evaluated the effects of a P4P scheme on utilisation of all maternal and child immunization services targeted by the scheme, and non-targeted general outpatient service use. We also evaluated effects on patient satisfaction with care and clinical content of antenatal care, and user costs. The evaluation was done in 150 facilities across all 7 intervention districts and 4 comparison districts with two rounds of data collection over 13-months in January 2012 and February 2013. We sampled 3000 households of women who had delivered in the 12 months prior to interview; 1500 patients attending health facilities for targeted and non-targeted services at each round of data collection. Difference-in-difference regression analysis was employed.
We estimated a significant positive effect on two out of eight targeted indicators. There was an 8.2% (95% CI: 3.6% to 12.8%) increase in coverage of institutional deliveries among women in the intervention area, and a 10.3% (95% CI: 4.4% to 16.1%) increase in the provision of anti-malarials during pregnancy. Use of non-targeted services reduced at dispensaries by 57.5 visits per month among children under five (95% CI: -110.2 to -4.9) and by 90.8 visits per month for those aged over five (95% CI: -156.5 to -25.2). There was no evidence of an effect of P4P on patient experience of care for targeted services. There was a 0.05 (95% CI: 0.01 to 0.10) increase in the patient satisfaction score for non-targeted services. P4P was associated with a 5.0% reduction in those paying out of pocket for deliveries (95% CI: -9.3% to -0.7%) but there was no evidence of an effect on the average amount paid.
This study adds to the very limited evidence on the effects of P4P at scale and highlights the potential risks of such schemes in relation to non-targeted service use. Further consideration of the design of P4P schemes is required to enhance progress towards universal health coverage, and close monitoring of effects on non-targeted services and user costs should be encouraged.
Even if cancer represents a burden for human society, an exhaustive cure has not been discovered yet. Low therapeutic index and resistance to pharmacotherapy are two of the major limits of antitumour ...treatments. Natural products represent an excellent library of bioactive molecules. Thus, tapping into the natural world may prove useful in identifying new therapeutic options with favourable pharmaco-toxicological profiles.
, or common walnut, is a very resilient tree that has inhabited our planet for thousands of years. Many studies correlate walnut consumption to beneficial effects towards several chronic diseases, such as cancer, mainly due to the bioactive molecules stored in different parts of the plant. Among others, polyphenols, quinones, proteins, and essential fatty acids contribute to its pharmacologic activity. The present review aims to offer a comprehensive perspective about the antitumour potential of the most promising compounds stored in this plant, such as juglanin, juglone, and the ellagitannin-metabolites urolithins or deriving from walnut dietary intake. All molecules and a chronic intake of the fruit provide tangible anticancer effects. However, the scarcity of studies on humans does not allow results to be conclusive.
Summary Background Tracking of financial resources to maternal, newborn, and child health provides crucial information to assess accountability of donors. We analysed official development assistance ...(ODA) flows to maternal, newborn, and child health for 2009 and 2010, and assessed progress since our monitoring began in 2003. Methods We coded and analysed all 2009 and 2010 aid activities from the database of the Organisation for Economic Co-operation and Development, according to a functional classification of activities and whether all or a proportion of the value of the disbursement contributed towards maternal, newborn, and child health. We analysed trends since 2003, and reported two indicators for monitoring donor disbursements: ODA to child health per child and ODA to maternal and newborn health per livebirth. We analysed the degree to which donors allocated ODA to 74 countries with the highest maternal and child mortality rates (Countdown priority countries) with time and by type of donor. Findings Donor disbursements to maternal, newborn, and child health activities in all countries continued to increase, to $6511 million in 2009, but slightly decreased for the first time since our monitoring started, to $6480 million in 2010. ODA for such activities to the 74 Countdown priority countries continued to increase in real terms, but its rate of increase has been slowing since 2008. We identified strong evidence that targeting of ODA to countries with high rates of maternal mortality improved from 2005 to 2010. Targeting of ODA to child health also improved but to a lesser degree. The share of multilateral funding continued to decrease but, relative to bilaterals and global health initiatives, was better targeted. Interpretation The recent slowdown in the rate of funding increases is worrying and likely to partly result from the present financial crisis. Tracking of donor aid should continue, to encourage donor accountability and to monitor performance in targeting aid flows to those in most need. Funding Bill & Melinda Gates Foundation; World Bank; Governments of Australia, Canada, Norway, Sweden, and the UK.
Cancer affects more than 19 million people and is the second leading cause of death in the world. One of the principal strategies used in cancer therapy is the inhibition of topoisomerase II, ...involved in the survival of cells. Side effects and adverse reactions limit the use of topoisomerase II inhibitors; hence, research is focused on discovering novel compounds that can inhibit topoisomerase II and have a safer toxicological profile. Marine organisms are a source of secondary metabolites with different pharmacological properties including anticancer activity. The objective of this review is to present and discuss the pharmacological potential of marine-derived compounds whose antitumor activity is mediated by topoisomerase II inhibition. Several compounds derived from sponges, fungi, bacteria, ascidians, and other marine sources have been demonstrated to inhibit topoisomerase II. However, some studies only report docking interactions, whereas others do not fully explain the mechanisms of topoisomerase II inhibition. Further in vitro and in vivo studies are needed, as well as a careful toxicological profile evaluation with a focus on cancer cell selectivity.
Summary Background Tracking of aid resources to reproductive, maternal, newborn, and child health (RMNCH) provides timely and crucial information to hold donors accountable. For the first time, we ...examine flows in official development assistance (ODA) and grants from the Bill & Melinda Gates Foundation (collectively termed ODA+) in relation to the continuum of care for RMNCH and assess progress since 2003. Methods We coded and analysed financial disbursements for maternal, newborn, and child health (MNCH) and for reproductive health (R*) to all recipient countries worldwide from all donors reporting to the creditor reporting system database for the years 2011–12. We also included grants from the Bill & Melinda Gates Foundation. We analysed trends for MNCH for the period 2003–12 and for R* for the period 2009–12. Findings ODA+ to RMNCH from all donors to all countries worldwide amounted to US$12·2 billion in 2011 (an 11·8% increase relative to 2010) and $12·8 billion in 2012 (a 5·0% increase relative to 2011). ODA+ to MNCH represents more than 60% of all aid to RMNCH. ODA+ to projects that have newborns as part of the target population has increased 34-fold since 2003. ODA to RMNCH from the 31 donors, which have reported consistently since 2003, to the 75 Countdown priority countries, saw a 3·2% increase in 2011 relative to 2010 ($8·3 billion in 2011), and an 11·8% increase in 2012 relative to 2011 ($9·3 billion in 2012). ODA to RMNCH projects has increased with time, whereas general budget support has continuously declined. Bilateral agencies are still the predominant source of ODA to RMNCH. Increased funding to family planning, nutrition, and immunisation projects were noted in 2011 and 2012. ODA+ has been targeted to RMNCH during the period 2005–12, although there is no evidence of improvements in targeting over time. Interpretation Despite a reduction in ODA+ in 2011, ODA+ to RMNCH increased in both 2011 and 2012. The increase in funding is encouraging, but continued increases are needed to accelerate progress towards achieving MDGs 4 and 5 and beyond. Funding Bill & Melinda Gates Foundation.
Summary Background Women's groups and health education by peer counsellors can improve the health of mothers and children. We assessed their effects on mortality and breastfeeding rates in rural ...Malawi. Methods We did a 2×2 factorial, cluster-randomised trial in 185 888 people in Mchinji district. 48 equal-sized clusters were randomly allocated to four groups with a computer-generated number sequence. 24 facilitators guided groups through a community action cycle to tackle maternal and child health problems. 72 trained volunteer peer counsellors made home visits at five timepoints during pregnancy and after birth to support breastfeeding and infant care. Primary outcomes for the women's group intervention were maternal, perinatal, neonatal, and infant mortality rates (MMR, PMR, NMR, and IMR, respectively); and for the peer counselling were IMR and exclusive breastfeeding (EBF) rates. Analysis was by intention to treat. The trial is registered as ISRCTN06477126. Findings We monitored outcomes of 26 262 births between 2005 and 2009. In a factorial model adjusted only for clustering and the volunteer peer counselling intervention, in women's group areas, for years 2 and 3, we noted non-significant decreases in NMR (odds ratio 0·93, 0·64–1·35) and MMR (0·54, 0·28–1·04). After adjustment for parity, socioeconomic quintile, and baseline measures, effects were larger for NMR (0·85, 0·59–1·22) and MMR (0·48, 0·26–0·91). Because of the interaction between the two interventions, a stratified analysis was done. For women's groups, in adjusted analyses, MMR fell by 74% (0·26, 0·10–0·70), and NMR by 41% (0·59, 0·40–0·86) in areas with no peer counsellors, but there was no effect in areas with counsellors (1·09, 0·40–2·98, and 1·38, 0·75–2·54). Factorial analysis for the peer counselling intervention for years 1–3 showed a fall in IMR of 18% (0·82, 0·67–1·00) and an improvement in EBF rates (2·42, 1·48–3·96). The results of the stratified, adjusted analysis showed a 36% reduction in IMR (0·64, 0·48–0·85) but no effect on EBF (1·18, 0·63–2·25) in areas without women's groups, and in areas with women's groups there was no effect on IMR (1·05, 0·82–1·36) and an increase in EBF (5·02, 2·67–9·44). The cost of women's groups was US$114 per year of life lost (YLL) averted and that of peer counsellors was $33 per YLL averted, using stratified data from single intervention comparisons. Interpretation Community mobilisation through women's groups and volunteer peer counsellor health education are methods to improve maternal and child health outcomes in poor rural populations in Africa. Funding Saving Newborn Lives, UK Department for International Development, and Wellcome Trust.
In this interdisciplinary study, we selected two compounds, namely, smenamide A, a peptide-polyketide, and smenolactone D, a polyketide, as models because they are representative of two different ...classes of molecules isolated from the marine sponge
. The organic extract of
was analyzed using a combination of high-resolution LC-MS/MS and molecular networking, a recently developed method for automated LC-MS data analysis. The analyses were targeted to highlight clusters made by chlorinated compounds present in the extracts. Then, the two model compounds were analyzed for their bioactivity. Data reported here show that smenamide A did not exhibit a cytotoxic effect, while smenolactone D was cytotoxic on different tumor cell lines and was able to induce different types of cell death, including ferroptosis and apoptosis.
ObjectivesToilet users often report valuing outcomes such as privacy and safety more highly than reduced disease, but effects of urban sanitation interventions on such outcomes have never been ...assessed quantitatively. In this study, we evaluate the impact of a shared sanitation intervention on quality of life (QoL) and mental well-being.DesignWe surveyed individuals living in intervention and control clusters of a recent non-randomised controlled trial, and used generalised linear mixed regression models to make an observational comparison of outcomes between arms.SettingLow-income unsewered areas of Maputo City, Mozambique.ParticipantsWe interviewed 424 participants, 222 from the prior trial’s intervention group and 202 from the control group.InterventionsThe control group used low-quality pit latrines. The intervention group received high-quality shared toilets, with users contributing 10%–15% of capital cost.OutcomesOur primary outcome was the Sanitation-related QoL (SanQoL) index, which applies respondent-derived weights to combine perceptions of sanitation-related disgust, privacy, safety, health and shame. Secondary outcomes were the WHO-5 mental well-being index and a sanitation Visual Analogue Scale.ResultsThe intervention group experienced a 1.6 SD gain in SanQoL compared with the control group. This adjusted SanQoL gain was 0.34 (95% CI 0.29 to 0.38) on a 0–1 scale with control mean 0.49. Effect sizes were largest for safety and privacy attributes. Intervention respondents also experienced a 0.2 SD gain in mental well-being. The adjusted gain was 6.2 (95% CI 0.3 to 12.2) on a 0–100 scale with control mean 54.4.ConclusionsQoL outcomes are highly valued by toilet users and can be improved by sanitation interventions. Such outcomes should be measured in future sanitation trials, to help identify interventions which most improve people’s lives. Since SanQoL weights are derived from respondent valuation, our primary result can be used in economic evaluation.
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