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This study estimates long-run impacts of a child health investment, exploiting community-wide experimental variation in school-based deworming. The program increased labor supply among men and education among women, with accompanying shifts in labor market specialization. Ten years after deworming treatment, men who were eligible as boys stay enrolled for more years of primary school, work 17% more hours each week, spend more time in nonagricultural self-employment, are more likely to hold manufacturing jobs, and miss one fewer meal per week. Women who were in treatment schools as girls are approximately one quarter more likely to have attended secondary school, halving the gender gap. They reallocate time from traditional agriculture into cash crops and nonagricultural self-employment. We estimate a conservative annualized financial internal rate of return to deworming of 32%, and show that mass deworming may generate more in future government revenue than it costs in subsidies.

Lack of education and an economic dependence on men are often suggested as important risk factors for HIV infection in women. We assessed the efficacy of a cash transfer programme to reduce the risk of sexually transmitted infections in young women. In this cluster randomised trial, never-married women aged 13–22 years were recruited from 176 enumeration areas in the Zomba district of Malawi and randomly assigned with computer-generated random numbers by enumeration area (1:1) to receive cash payments (intervention group) or nothing (control group). Intervention enumeration areas were further randomly assigned with computer-generated random numbers to conditional (school attendance required to receive payment) and unconditional (no requirements to receive payment) groups. Participants in both intervention groups were randomly assigned by a lottery to receive monthly payments ranging from US$1 to $5, while their parents were independently assigned with computer-generated random numbers to receive $4–10. Behavioural risk assessments were done at baseline and 12 months; serology was tested at 18 months. Participants were not masked to treatment status but counsellors doing the serologic testing were. The primary outcomes were prevalence of HIV and herpes simplex virus 2 (HSV-2) at 18 months and were assessed by intention-to-treat analyses. The trial is registered, number NCT01333826. 88 enumeration areas were assigned to receive the intervention and 88 as controls. For the 1289 individuals enrolled in school at baseline with complete interview and biomarker data, weighted HIV prevalence at 18 month follow-up was 1·2% (seven of 490 participants) in the combined intervention group versus 3·0% (17 of 799 participants) in the control group (adjusted odds ratio [OR] 0·36, 95% CI 0·14–0·91); weighted HSV-2 prevalence was 0·7% (five of 488 participants) versus 3·0% (27 of 796 participants; adjusted OR 0·24, 0·09–0·65). In the intervention group, we noted no difference between conditional versus unconditional intervention groups for weighted HIV prevalence (3/235 [1%] vs 4/255 [2%]) or weighted HSV-2 prevalence (4/233 [1%] vs 1/255 [<1%]). For individuals who had already dropped out of school at baseline, we detected no significant difference between intervention and control groups for weighted HIV prevalence (23/210 [10%] vs 17/207 [8%]) or weighted HSV-2 prevalence (17/211 [8%] vs 17/208 [8%]). Cash transfer programmes can reduce HIV and HSV-2 infections in adolescent schoolgirls in low-income settings. Structural interventions that do not directly target sexual behaviour change can be important components of HIV prevention strategies. Global Development Network, Bill & Melinda Gates Foundation, National Bureau of Economic Research Africa Project, World Bank's Research Support Budget, and several World Bank trust funds (Gender Action Plan, Knowledge for Change Program, and Spanish Impact Evaluation fund).

Background Adolescents living with HIV face substandard outcomes along the continuum of care, including higher rates of poor adherence and virologic failure. Support groups have been identified as a method to improve adherence, but there is insufficient evidence regarding their effectiveness. This study seeks to examine the protective influences for and barriers to antiretroviral therapy (ART) adherence in HIV-positive adolescents living in Tanzania. Methods This is a qualitative study conducted in Tanzania from January to March 2018. The sample of adolescents aged 10-19 ( n  = 33) was purposefully selected based on age, gender, and support group attendance to capture a broad range of experiences. Participants completed an in-depth interview, covering topics such as retention in HIV services, support group experiences, and joys and challenges of adolescent life. Interviews were coded and themes related to ART adherence were identified and summarized. Results Support groups helped promote adherence by improving adolescents’ knowledge and confidence. Participants associated joining support groups with an improvement in health. Almost every participant described the significant positive influence a treatment supporter had on adherence. Adolescents’ daily schedules and emotional state served as a barrier to adherence. Furthermore, adherence was negatively impacted by participants’ fear of accidental disclosure. Conclusion Logistical and psychosocial factors can hinder adherence. Interventions that provide both education and psychosocial support, such as peer support groups, have the potential to improve health outcomes for this population, but may not address more persistent barriers to adherence rooted in lack of treatment support from family members or friends who have not been disclosed to, or lack of transportation funds/food security.

Health and income are strongly correlated both within and across countries, yet the extent to which improvements in income have a causal effect on health status remains controversial. We investigate whether short-term fluctuations in aggregate income affect infant mortality using an unusually large data set of 1.7 million births in 59 developing countries. We show a large, negative association between per capita GDP and infant mortality. Female infant mortality is more sensitive than male infant mortality to negative economic shocks, suggesting that policies that protect the health status of female infants may be especially important during economic downturns.

PurposeAnti-helmintic drugs mebendazole and albendazole are commonly used to treat a variety of parasitic infections. They have recently shown some promising results in pre-clinical in vitro and in vivo anti-cancer studies.MethodsWe compare their efficacy in breast and colon cancer cell lines as well as in non-cancerous cells and elucidate their mechanism of action. The drugs were screened for cytotoxicity in MDA-MB-231, MCF-7 (breast cancer), HT-29 (colorectal cancer), and mesenchymal stromal cells, using the MTT assay. Their effects on the cell cycle, tubulin levels, and cell death mechanisms were analysed using flow cytometry and fluorescent microscopy.ResultsMebendazole and albendazole were found to selectively kill cancer cells, being most potent in the colorectal cancer cell line HT-29, with both drugs having IC50 values of less than 1 µM at 48 h. Both mebendazole and albendazole induced classical apoptosis characterised by caspase-3 activation, phosphatidylserine exposure, DNA fragmentation, mitochondrial membrane permeability, and reactive oxygen species production. Cell cycle arrest in the G2/M phase was found, and tubulin polymerisation was disrupted.ConclusionMebendazole and albendazole were shown to cause selective cancer cell death via a mechanism of classical apoptosis and cell cycle arrest, involving the destabilisation of microtubules.

TIMP-3 is one of four tissue inhibitors of matrix metalloproteinases, the endogenous inhibitors of the matrix metalloproteinase enzymes. These enzymes have an important role in metastasis, in the invasion of cancer cells through the basement membrane and extracellular matrix. TIMP-1, -2 and -4 both promote and inhibit tumour development, in a context-dependent manner, however TIMP-3 is consistently anti-tumourigenic. TIMP-3 is also the only insoluble member of the family, being either bound to the extracellular matrix or the low density lipoprotein-related protein-1, through which it can be endocytosed. Levels of TIMP-3 have also been shown to be regulated by micro RNAs and promoter hypermethylation, resulting in frequent silencing in many tumour types, to the extent that its expression has been suggested as a prognostic marker in some tumours, being associated with lower levels of metastasis, or better response to treatment. TIMP-3 has been shown to have anti-metastatic effects, both through inhibition of matrix metalloproteinases and ADAM family members and downregulation of angiogenesis. This occurs via interactions with receptors including VEGF, via modulation of signaling pathways and due to protease inhibition. TIMP-3 has also been shown to reduce tumour growth rate, most often by inducing apoptosis by stabilisation of death receptors. A number of successful mechanisms of delivery of TIMP-3 to tumour or inflammatory sites have been investigated in vitro or in animal studies. It may therefore be worthwhile further exploring the use of TIMP-3 as a potential anti-metastatic or anti-tumorigenic therapy for many tumour types.

The COVID-19 pandemic and associated risk-mitigation strategies have altered the social contexts in which adolescents in low- and middle-income countries live. Little is known, however, about the impacts of the pandemic on displaced populations, and how those impacts differ by gender and life stage. We investigate the extent to which the pandemic has compounded pre-existing social inequalities among adolescents in Jordan, and the role support structures play in promoting resilience. Our analysis leverages longitudinal quantitative survey data and in-depth qualitative interviews, collected before and after the onset of COVID-19, with over 3,000 Syrian refugees, stateless Palestinians and vulnerable Jordanians, living in camps, host communities and informal tented settlements. We utilize mixed-methods analysis combining multivariate regression with deductive qualitative tools to evaluate pandemic impacts and associated policy responses on adolescent wellbeing and mental health, at three and nine months after the pandemic onset. We also explore the role of support systems at individual, household, community, and policy levels. We find the pandemic has resulted in severe economic and service disruptions with far-reaching and heterogenous effects on adolescent wellbeing. Nine months into the pandemic, 19.3% of adolescents in the sample presented with symptoms of moderate-to severe depression, with small signs of improvement (3.2 percentage points [pp], p<0.001). Two thirds of adolescents reported household stress had increased during the pandemic, especially for Syrian adolescents in host communities (10.7pp higher than any other group, p<0.001). Social connectedness was particularly low for girls, who were 13.4 percentage points (p<0.001) more likely than boys to have had no interaction with friends in the past 7 days. Adolescent programming shows signs of being protective, particularly for girls, who were 8.8 percentage points (p<0.01) more likely to have a trusted friend than their peers who were not participating in programming. Pre-existing social inequalities among refugee adolescents affected by forced displacement have been compounded during the COVID-19 pandemic, with related disruptions to services and social networks. To achieve Sustainable Development Goal targets to support healthy and empowered development in adolescence and early adulthood requires interventions that target the urgent needs of the most vulnerable adolescents while addressing population-level root causes and determinants of psychosocial wellbeing and resilience for all adolescent girls and boys.

Background Access to sexual and reproductive health services is an explicit element of the Sustainable Development Goals, and is critical for achieving family planning goals and broader well-being of young people. Youth (15–24 years) face many barriers to accessible, quality services, and refugees often experience additional barriers due to physical, economic, legal and/or social exclusion. This study explored these barriers in the context of Jordan, a country that has one of the highest proportions of refugees globally. Methods This concurrent mixed-methods study utilizes the 2022–2023 Gender and Adolescence: Global Evidence survey data collected from 313 married female youth living in Jordan to describe utilization of contraceptives among Jordanians and Syrian refugees, exploring the role of residence (formal refugee camp, host community or informal tented settlement) and factors associated with contraceptive use among Syrian refugees. A multivariable linear probability model and qualitative data from in-depth individual interviews and focus group discussions were used to explore underlying factors driving differences in contraceptive utilization among Syrian refugee youth. Results The survey found that 63.4% of Jordanian youth and 42.8% of Syrian refugee youth were recently using contraception, with notable differences in type of contraceptive method used by both refugee status and residence. Among Syrian refugee youth, living in a host community emerged as a key factor associated with contraceptive use, as it was associated with a 19.6 percentage point increase in the likelihood of using contraception compared to those living in refugee camps. Qualitative themes nuance these findings, suggesting that living in a refugee camp where there is more restricted access to healthcare services, more salient social norms, and limited knowledge about reproductive health present barriers to contraceptive use for Syrian refugee youth. Conclusions These results highlight that youth-friendly reproductive health services are having mixed efficacy in Jordan. Understanding barriers to contraception should inform family planning services for marginalized groups like Syrian refugee youth. There is a need for evidence-informed efforts to expand provision of family planning counselling and access to contraceptives for young married couples in Jordan, and especially for those living in formal refugee camps.

The basic economic model of labor supply has a very clear prediction of what we should expect when an adult receives an unexpected cash windfall: they should work less and earn less. This intuition underlies concerns that many types of cash transfers, ranging from government benefits to migrant remittances, will undermine work ethics and make recipients lazy. We discuss a range of additional channels to this simple labor-leisure trade-off that can make this intuition misleading in low- and middle-income countries, including missing markets, price effects from conditions attached to transfers, and dynamic and general equilibrium effects. We use this as a lens through which to examine the evidence on the adult labor market impacts of a wide range of cash transfer programs: government transfers, charitable giving and humanitarian transfers, remittances, cash assistance for job search, cash transfers for business start-up, and bundled interventions. Overall, cash transfers that are made without an explicit employment focus (such as conditional and unconditional cash transfers, and remittances) tend to result in little to no change in adult labor. The main exceptions are transfers to the elderly and to some refugees, who reduce work. In contrast, transfers made for job search assistance or business start-up tend to increase adult labor supply and earnings, with the likely main channels being the alleviation of liquidity and risk constraints.

Malignant melanoma is a highly metastatic tumour, resistant to treatment. Serotonin type-3 (5-HT3) receptor antagonists, such as tropisetron and ondansetron, are well-tolerated antiemetic drugs commonly used to prevent nausea caused by chemotherapy or radiotherapy. We investigated the anticancer effects of these drugs on melanoma cancer cell lines WM-266–4 and B16F10 with or without paclitaxel. We constructed IC50 curves and performed Chou–Talalay analysis, using data obtained with the MTT assay. Flow cytometry and fluorescent microscopy were used to examine characteristics of the cell cycle, cell death and cytoskeleton changes. Protein levels and activation were analysed by western blotting and molecular docking studies carried out. Data were analysed by one way ANOVA and post hoc testing. Ondansetron and tropisetron showed selective concentration-dependent cytotoxicity in melanoma cell lines WM-266–4 and B16F10. The effect in combination with paclitaxel was synergistic. The drugs did not cause cell cycle arrest but did promote characteristics of classical apoptosis, including accumulation of subG1 DNA, cleaved caspase-3, mitochondrial membrane permeability and phosphatidylserine exposure. As well, the cytosolic calcium level in the melanoma cells was enhanced, phosphorylated ERK1/2 induced and NF-κB inhibited. Finally, the formation of microtubules was shown to be impaired in melanoma cells treated with ondansetron or tropisetron. Docking studies were used to predict that these drugs could bind to the colchicine binding site on the tubulin molecule. Antiemetic drugs, already given in combination with chemotherapy, may enhance the cytotoxic effect of chemotherapy, following successful delivery to the tumour site.