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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.

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. Juglans regia, 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.

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.

Psychosocial interventions for adolescent mental health problems are effective, but evidence on their longer-term outcomes is scarce, especially in low-resource settings. We report on the 12-month sustained effectiveness and costs of scaling up a lay counselor-delivered, transdiagnostic problem-solving intervention for common adolescent mental health problems in low-income schools in New Delhi, India. Participants in the original trial were 250 school-going adolescents (mean [M] age = 15.61 years, standard deviation [SD] = 1.68), including 174 (69.6%) who identified as male. Participants were recruited from 6 government schools over a period of 4 months (August 20 to December 14, 2018) and were selected on the basis of elevated mental health symptoms and distress/functional impairment. A 2-arm, randomized controlled trial design was used to examine the effectiveness of a lay counselor-delivered, problem-solving intervention (4 to 5 sessions over 3 weeks) with supporting printed booklets (intervention arm) in comparison with problem solving delivered via printed booklets alone (control arm), at the original endpoints of 6 and 12 weeks. The protocol was modified, as per the recommendation of the Trial Steering Committee, to include a post hoc extension of the follow-up period to 12 months. Primary outcomes were adolescent-reported psychosocial problems (Youth Top Problems [YTP]) and mental health symptoms (Strengths and Difficulties Questionnaire [SDQ] Total Difficulties scale). Other self-reported outcomes included SDQ subscales, perceived stress, well-being, and remission. The sustained effects of the intervention were estimated at the 12-month endpoint and over 12 months (the latter assumed a constant effect across 3 follow-up points) using a linear mixed model for repeated measures and involving complete case analysis. Sensitivity analyses examined the effect of missing data using multiple imputations. Costs were estimated for delivering the intervention during the trial and from modeling a scale-up scenario, using a retrospective ingredients approach. Out of the 250 original trial participants, 176 (70.4%) adolescents participated in the 12-month follow-up assessment. One adverse event was identified during follow-up and deemed unrelated to the intervention. Evidence was found for intervention effects on both SDQ Total Difficulties and YTP at 12 months (YTP: adjusted mean difference [AMD] = -0.75, 95% confidence interval [CI] = -1.47, -0.03, p = 0.04; SDQ Total Difficulties: AMD = -1.73, 95% CI = -3.47, 0.02, p = 0.05), with stronger effects over 12 months (YTP: AMD = -0.98, 95% CI = -1.51, -0.45, p < 0.001; SDQ Total Difficulties: AMD = -1.23, 95% CI = -2.37, -0.09; p = 0.03). There was also evidence for intervention effects on internalizing symptoms, impairment, perceived stress, and well-being over 12 months. The intervention effect was stable for most outcomes on sensitivity analyses adjusting for missing data; however, for SDQ Total Difficulties and impairment, the effect was slightly attenuated. The per-student cost of delivering the intervention during the trial was $3 United States dollars (USD; or $158 USD per case) and for scaling up the intervention in the modeled scenario was $4 USD (or $23 USD per case). The scaling up cost accounted for 0.4% of the per-student school budget in New Delhi. The main limitations of the study's methodology were the lack of sample size calculations powered for 12-month follow-up and the absence of cost-effectiveness analyses using the primary outcomes. In this study, we observed that a lay counselor-delivered, brief transdiagnostic problem-solving intervention had sustained effects on psychosocial problems and mental health symptoms over the 12-month follow-up period. Scaling up this resource-efficient intervention is an affordable policy goal for improving adolescents' access to mental health care in low-resource settings. The findings need to be interpreted with caution, as this study was a post hoc extension, and thus, the sample size calculations did not take into account the relatively high attrition rate observed during the long-term follow-up. ClinicalTrials.gov NCT03630471.

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. 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. 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. 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. 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.

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. 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. 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. 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. Saving Newborn Lives, UK Department for International Development, and Wellcome Trust.

Background School attendance and completion among girls protect them from multiple sexual and reproductive health problems. However, inadequate resources for managing menstruation remains a barrier to school participation and learning in low- and middle-income countries. With the increased global focus on closing the gender gap in education, schoolgirls’ voices are important in understanding drivers of suboptimal social and school participation during menstruation. This paper explores how menstruation influences social and school participation from the perspectives of schoolgirls. Methods We conducted 40 in-depth interviews with purposively-selected secondary schoolgirls aged 13–20 years in two rural and two urban schools in Northern Tanzania from 2021 to 2022. To be eligible for participation, the schoolgirls must have reported missing school during their last menstruation. We used an in-depth interview guide to elicit girls’ menstrual experiences and how such experience influenced their school and social participation. We used NVivo 12 software to code data and employed thematic analysis using the social-ecological model. Results The respondents described the drivers of suboptimal social and school participation at the individual level (negative menstrual experience, i.e. menstrual pain and constant worries of menstrual blood leaking, and individual economic constraints); interpersonal level (the fear of menstrual status disclosure, and peer’s attitude); school level (inadequate emergency pad at school, lack of private place to change, and unhygienic school WASH); and societal level socio-cultural restrictions (girls are prohibited from touching plants/vegetables, engaging in household chores/religious worship, or physical contact with men during menstruation, and refusal to use conventional painkillers to relief menstrual pain). Conclusions The findings suggest that drivers of suboptimal social and school participation among secondary schoolgirls exist at the individual, interpersonal relationship, school, and societal levels. Multi-level evidence-based multicomponent interventions to improve menstrual health at all socio-ecological levels are warranted for optimal social and school participation among schoolgirls.

Background The vast majority of refugees are hosted in low and middle income countries (LMICs), which are already struggling to finance and achieve universal health coverage for their own populations. While there is mounting evidence of barriers to health care access facing refugees, there is more limited evidence on equity in access to and affordability of care across refugee and host populations. The objective of this study was to examine equity in terms of health needs, service utilisation, and health care payments both within and between South Sudanese refugees and hosts communities (Ugandan nationals), in two districts of Uganda. Methods Participants were recruited from host and refugee villages from Arua and Kiryandongo districts. Twenty host villages and 20 refugee villages were randomly selected from each district, and 30 households were sampled from each village, with a target sample size of 2400 households. The survey measured condition incidence, health care seeking and health care expenditure outcomes related to acute and chronic illness and maternal care. Equity was assessed descriptively in relation to household consumption expenditure quintiles, and using concentration indices and Kakwani indices (for expenditure outcomes). We also measured the incidence of catastrophic health expenditure- payments for healthcare and impoverishment effects of expenditure across wealth quintiles. Results There was higher health need for acute and chronic conditions in wealthier groups, while maternal care need was greater among poorer groups for refugees and hosts. Service coverage for acute, chronic and antenatal care was similar among hosts and refugee communities. However, lower levels of delivery care access for hosts remain. Although maternal care services are now largely affordable in Uganda among the studied communities, and service access is generally pro-poor, the costs of acute and chronic care can be substantial and regressive and are largely responsible for catastrophic expenditures, with service access benefiting wealthier groups. Conclusions Efforts are needed to enhance access among the poorest for acute and chronic care and reduce associated out-of-pocket payments and their impoverishing effects. Further research examining cost drivers and potential financing arrangements to offset these will be important.

Ebola Virus Disease (EVD) presents significant global health challenges, including high mortality and substantial physical morbidity among patients and survivors. Beyond immediate health impacts, EVD survivors, frontline healthcare workers, and community members face profound mental health and psychosocial issues. Over 35 EVD outbreaks have occurred in Africa since 1976, often in the context of fragile health systems and chronic conflict, complicating the response to mental health needs. Uganda has experienced seven outbreaks, the latest from September 20, 2022, to January 11, 2023, affecting nine districts, with Mubende as the epicenter. The Mental Health Focus Area of the Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine, Uganda Research Unit, in collaboration with Uganda’s Ministry of Health, has initiated the development and piloting of the Ebola+D mental health intervention to address the medium- and long-term mental health consequences of Ebola in the Mubende district. This intervention will be a collaborative stepped care model based on the successful HIV + D intervention in Uganda and the MANAS intervention in India. Participatory, theory-informed approaches will be employed in Mubende district to develop the Ebola+D mental health intervention. This will involve five phases: i) adaptation of the HIV + D collaborative stepped care mental health intervention into primary health care in Mubende district to produce the Ebola+D mental health intervention; ii) adaptation and translation of the Problem Solving Therapy for Primary Care (PST-PC) treatment manual to the local rural situation in Mubende district; iii) a pilot study to evaluate the acceptability, feasibility and impact of the Ebola+D mental health intervention on mental health outcomes; iv) a health economics component to examine the costs of the Ebola + D mental health intervention; and v) a qualitative component to explore the Ebola virus disease (EVD) associated negative beliefs and lived out experiences of affected members of the community. The findings from this study will inform future mental health and psychosocial interventions secondary to outbreaks of Emerging Viral Diseases (such as EVD) in low resourced settings such those in sub-Saharan Africa.