Increasing Production Diversity and Diet Quality: Evidence from Bangladesh.

In the context of rural Bangladesh, we assess whether agriculture training alone, nutrition Behavior Communication Change (BCC) alone, combined agriculture training and nutrition BCC, or agriculture training and nutrition BCC combined with gender sensitization improve: (a) production diversity, either on household fields or through crop, livestock or aquaculture activities carried out near the family homestead and (b) diet diversity and the quality of household diets. All treatment arms were implemented by government employees. Implementation quality was high. No treatment increased production diversification of crops grown on fields. Treatment arms with agricultural training did increase the number of different crops grown in homestead gardens and the likelihood of any egg, dairy, or fish production but the magnitudes of these effect sizes were small. All agricultural treatment arms had, in percentage terms, large effects on measures of levels of homestead production. However, because baseline levels of production were low, the magnitude of these changes in absolute terms was modest. Nearly all treatment arms improved measures of food consumption and diet with the largest effects found when nutrition and agriculture training were combined. Relative to treatments combining agriculture and nutrition training, we find no significant impact of adding the gender sensitization on our measures of production diversity or diet quality. Interventions that combine agricultural training and nutrition BCC can improve both production diversity and diet quality, but they are not a panacea. They can, however, contribute towards better diets of rural households.

Leishmania exploits host cAMP/EPAC/calcineurin signaling to induce an IL-33-mediated anti-inflammatory environment for the establishment of infection.

Host anti-inflammatory responses are critical for the progression of visceral leishmaniasis, and the pleiotropic cytokine interleukin (IL)-33 was found to be upregulated in infection. Here, we documented that IL-33 induction is a consequence of elevated cAMP-mediated exchange protein activated by cAMP (EPAC)/calcineurin-dependent signaling and essential for the sustenance of infection. Leishmania donovani-infected macrophages showed upregulation of IL-33 and its neutralization resulted in decreased parasite survival and increased inflammatory responses. Infection-induced cAMP was involved in IL-33 production and of its downstream effectors PKA and EPAC, only the latter was responsible for elevated IL-33 level. EPAC initiated Rap-dependent phospholipase C activation, which triggered the release of intracellular calcium followed by calcium/calmodulin complex formation. Screening of calmodulin-dependent enzymes affirmed involvement of the phosphatase calcineurin in cAMP/EPAC/calcium/calmodulin signaling-induced IL-33 production and parasite survival. Activated calcineurin ensured nuclear localization of the transcription factors, nuclear factor of activated T cell 1 and hypoxia-inducible factor 1 alpha required for IL-33 transcription, and we further confirmed this by chromatin immunoprecipitation assay. Administering specific inhibitors of nuclear factor of activated T cell 1 and hypoxia-inducible factor 1 alpha in BALB/c mouse model of visceral leishmaniasis decreased liver and spleen parasite burden along with reduction in IL-33 level. Splenocyte supernatants of inhibitor-treated infected mice further documented an increase in tumor necrosis factor alpha and IL-12 level with simultaneous decrease of IL-10, thereby indicating an overall disease-escalating effect of IL-33. Thus, this study demonstrates that cAMP/EPAC/calcineurin signaling is crucial for the activation of IL-33 and in effect creates anti-inflammatory responses, essential for infection.

Antileishmanial activity of cathelicidin and its modulation by Leishmania donovani in a CREM-dependent manner for establishing infection.

Concerns regarding toxicity and resistance of current drugs have been reported in visceral leishmaniasis. Anti-microbial peptides are considered as new promising candidates and amongst them, human cathelicidin hCAP18/LL-37 showed significant parasite killing on drug-sensitive and resistant Leishmania promastigotes, coupled with its apoptosis-inducing role. Administration of hCAP18/LL-37 in infected macrophages also decreased parasite survival and increased the host favorable cytokine IL-12. However, 1,25-dihydroxyvitamin D3 (VitD3)-induced endogenous hCAP18/LL-37 production was hampered in infected THP-1 cells. Infection also suppressed the VitD3-receptor (VDR), transcription factor of hCAP18/LL-37. cAMP response element modulator (CREM), the repressor of VDR, was induced in infection resulting in suppression of both VDR and cathelicidin expression. PGE2/cAMP/PKA axis was found to regulate CREM induction during infection and silencing CREM in infected cells and BALB/c mice led to decreased parasite survival. Present study thus documents the anti-leishmanial potential of cathelicidin and further identifies CREM as a repressor of cathelicidin in Leishmania infection.

Corrigendum to "Diets of Men and Women in Rural Bangladesh are Equitable but Suboptimal" [Current Developments in Nutrition (2023), Volume 7, Issue 7].

[This corrects the article DOI: 10.1016/j.cdnut.2023.100107.].

PD-1 negatively tunes macrophage immune activation by turning off JNK and STAT1 signaling: Exploited by Leishmania for its intra-macrophage survival.

The anti-inflammatory role of the programmed death-1 receptor (PD-1) is well appreciated. However, the mechanism of how PD-1 signaling inhibits the pro-inflammatory cytokine responses in macrophages, which is further exploited by Leishmania to foster their intracellular survival, was unknown. We found that among three major MAP kinases regulating immune activation, PD-1 signaling decreased only JNK phosphorylation without perturbing p38 and ERK. Inflammatory transcription factor STAT1 was also inhibited by PD-1. Association studies documented that SHP, the downstream phosphatase of PD-1, is directly responsible for the decreased phosphorylation of JNK and STAT1. JNK and STAT1 deactivation led to Elk-1/c-Fos inhibition, which significantly decreased IL-12 and TNF-α levels. Further investigation revealed c-Fos deactivation ultimately rendered transcription factor AP1 inactive and facilitating parasite-favorable anti-inflammatory environment.

Comparing delivery channels to promote nutrition-sensitive agriculture: A cluster-randomized controlled trial in Bangladesh.

We use a randomized controlled trial in rural Bangladesh to compare two models of delivering nutrition content jointly to husbands and wives: deploying female nutrition workers versus mostly male agriculture extension workers. Both approaches increased nutrition knowledge of men and women, household and individual diet quality, and women's empowerment. Intervention effects on agriculture and nutrition knowledge, agricultural production diversity, dietary diversity, women's empowerment, and gender parity do not significantly differ between models where nutrition workers versus agriculture extension workers provide the training. The exception is in an attitudes score, where results indicate same-sex agents may affect scores differently than opposite-sex agents. Our results suggest opposite-sex agents may not necessarily be less effective in providing training. In South Asia, where agricultural extension systems and the pipeline to those systems are male-dominated, training men to deliver nutrition messages may offer a temporary solution to the shortage of female extension workers and offer opportunities to scale and promote nutrition-sensitive agriculture. However, in both models, we find evidence that the presence of mothers-in-law within households modifies the programs' effectiveness on some nutrition, empowerment, and attitude measures, suggesting that accounting for other influential household members is a potential area for future programming.

Diets of Men and Women in Rural Bangladesh Are Equitable but Suboptimal.

Background: Recent evidence suggests that diet inequities between men and women may have diminished within rural Bangladeshi households. However, this has not been directly tested with appropriate physiologic adjustments and it is unclear whether changes have occurred across socioeconomic strata. Understanding intrahousehold dietary patterns at different points on the income and food-security distribution in rural Bangladesh-particularly, within ultrapoor and farm households-is important for appropriate design of gender-sensitive and nutrition-sensitive interventions, which often target these groups. Objective: Using 2012 and 2016 data, we aimed to examine gender differences in diet quantity and quality among ultrapoor and farm households in rural Bangladesh. Methods: The study used baseline 24-h dietary data from 2 randomized control trials conducted in rural Bangladesh: the Transfer Modality Research Initiative (ultrapoor households) and the Agriculture, Nutrition, and Gender Linkages project (farm households). Ordinary least squares regressions with household-level fixed effects tested for gender differences among constructed diet measures, such as caloric intake, caloric adequacy ratio, dietary diversity score, global diet quality score, and probability of consuming moderate or high levels of healthy food groups. Results: In both samples, on average, women consumed fewer calories than men in the same households but consumed near equal or more in reference to their caloric needs. Women scored <1% lower than men on diet quality indicators and showed similar probabilities to men of consuming healthy foods. Most men and women in both samples were calorically inadequate (>60%) and recorded poor diet quality scores that indicated high risk of nutrient inadequacy and chronic disease (>95%). Conclusions: In both ultrapoor and farm households, although men record higher intake quantities and diet quality scores, the apparent male advantage disappear when energy requirements and the magnitudes of difference are considered. Diets of men and women in these rural Bangladeshi households are equitable but suboptimal.

Trust and distrust in low-income Michigan residents during the early COVID-19 pandemic: A qualitative study.

BACKGROUND: Trust and distrust have shaped health behaviour during the COVID-19 pandemic. Since the start of the pandemic, misinformation and polarization eroded trust across the United States. In states like Michigan, pandemic restrictions led to significant unrest. Michiganders also faced disproportionate morbidity and mortality from COVID-19 during this period. OBJECTIVE: The objective of this qualitative study was to understand the individual experiences of trust in low-income Michiganders during the early COVID-19 pandemic. PARTICIPANTS: Twenty-four participants at or below 200% of the federal poverty line who resided in Michigan were recruited for this study. APPROACH: Interviews were conducted during the winter of 2020 using a formal interview guide that addressed sources of information, perceptions of risk and exposure, protective behaviours and impacts of the pandemic at home, work and in receiving healthcare. RESULTS: Thematic analysis showed that themes of trust and distrust emerged in multiple facets of our participants' experiences, including in the context of information sources, the behaviours of others, health, financial security, employment and overall safety. Trust and distrust in low-income communities often stemmed from significant financial and economic vulnerabilities and instability in access to healthcare that was exacerbated in the pandemic. Furthermore, participant trust was shaped by internal (e.g., relationships with others) and external (e.g., source of information, social inequity) factors that influenced their perceptions and experiences during the pandemic. CONCLUSION: Trust has played an important role in many aspects of the experiences of low-income communities during the COVID-19 pandemic. This is important for clinicians to consider as COVID-19 becomes endemic, and trust continues to impact patients' approaches to vaccines, testing and treatment options. PATIENT OR PUBLIC CONTRIBUTION: This study was designed and conducted with the assistance and input of the members of the DECIDERS Steering Committee, a diverse statewide network of community members in Michigan. The DECIDERS team allows community members to have a voice in the design and conduct of health research, and collaborates with researchers to improve health across the state of Michigan.

Development and validation of a health and nutrition module for the project-level Women's Empowerment in Agriculture Index (pro-WEAI+HN).

Agricultural development projects increasingly aim to improve health and nutrition outcomes, often by engaging women. Although evidence shows such projects can improve women's and children's health and nutrition and empower women, little is known about their impacts on women's health- and nutrition-related agency and the extent to which impacts emerge through women's empowerment, largely due to a lack of instruments that measure the dimensions of women's agency that are directly relevant to health and nutrition outcomes. We developed an optional, complementary module for the project-level women's empowerment in agriculture index (pro-WEAI) to measure health- and nutrition-related agency (pro-WEAI + HN). Our method for developing related indicators used data collected from six agricultural development programmes implemented across Bangladesh, Burkina Faso and Mali (pooled sample = 12,114) and applied psychometric analysis (exploratory and confirmatory factor analysis) and the Alkire-Foster methodology. Results revealed seven indicators covering women's agency in the areas of her own health and diet; her health and diet during pregnancy; her child's diet; breastfeeding and weaning; purchasing food and health products; and acquiring food and health products. Multigroup confirmatory factor analysis revealed measurement invariance across contexts and samples. Tests of association (Cramer's V) and redundancy suggest that the pro-WEAI + HN indicators measured aspects of agency that are distinct from the core pro-WEAI. The uptake of these indicators in studies of nutrition-sensitive agricultural development projects may strengthen the evidence on how such programming can enhance women's empowerment to improve health and nutrition outcomes for themselves and their children.

Mannose-Decorated Composite Peptide Hydrogel with Thixotropic and Syneresis Properties and its Application in Treatment of Leishmaniasis.

Leishmaniasis, caused by the intramacrophage protozoan parasite Leishmania donovani, is a life-threatening yet neglected vector-borne disease. Few medications for the treatment of this disease are available. However, targeted delivery of drugs to macrophages remains a significant concern. Macrophages are equipped with many receptors, and therefore putting suitable ligands in the macrophage targeting drug delivery vehicle gained a lot of attention. One such receptor is the mannose receptor, abundantly expressed by macrophages. To treat this deadly disease, in this study, a mannose containing composite hydrogel is prepared by combining a self-aggregating short peptide (Nap-FFGE-NH2 , Pep-A) and a mannose containing non-aggregating peptide (Nap-FF-mannosyl, Pep-B). The self-aggregation of the composite hydrogel is evaluated using various spectroscopic and microscopic techniques. Intermolecular hydrogen bonding and π-π stacking lead to an antiparallel ß-sheet like arrangement of the peptides. Notably, the composite hydrogel showed shear-thinning and syneresis properties. Moreover, the composite hydrogel was found to be stable in cell-culture media, biodegradable and non-toxic to the macrophages. Both control and infected macrophages showed effective cell growth and proliferation when subjected to the composite 2D and 3D hydrogel matrix. When treated with Amphotericin B loaded composite hydrogel, the drug was effectively delivered to kill the parasite in the infected macrophages. Almost 3.5 fold decrease in the parasite burden was recorded when infected cells were treated with drug-loaded composite hydrogel. The injectability, biodegradability, non-cytotoxicity, and efficient drug delivery properties of the mannose-functionalized hydrogel make it a suitable candidate for the treatment of Leishmaniasis.

Translationally Controlled Tumor Protein-Mediated Stabilization of Host Antiapoptotic Protein MCL-1 Is Critical for Establishment of Infection by Intramacrophage Parasite Leishmania donovani.

In the early phase of infection, the intramacrophage pathogen Leishmania donovani protects its niche with the help of the antiapoptotic protein myeloid cell leukemia-1 (MCL-1). Whether Leishmania could exploit MCL-1, an extremely labile protein, at the late phase is still unclear. A steady translational level of MCL-1 observed up to 48 h postinfection and increased caspase-3 activity in MCL-1-silenced infected macrophages documented its importance in the late hours of infection. The transcript level of MCL-1 showed a sharp decline at 6 h postinfection, and persistent MCL-1 expression in cyclohexamide-treated cells negates the possibility of de novo protein synthesis, thereby suggesting infection-induced stability. Increased ubiquitination, a prerequisite for proteasomal degradation of MCL-1, was also found to be absent in the late hours of infection. Lack of interaction with its specific E3 ubiquitin ligase MULE (MCL-1 ubiquitin ligase E3) and specific deubiquitinase USP9X prompted us to search for blockade of the ubiquitin-binding site in MCL-1. To this end, TCTP (translationally controlled tumor protein), a well-known binding partner of MCL-1 and antiapoptotic regulator, was found to be strongly associated with MCL-1 during infection. Phosphorylation of TCTP, a requirement for MCL-1 binding, was also increased in infected macrophages. Knockdown of TCTP decreased MCL-1 expression and short hairpin RNA-mediated silencing of TCTP in an infected mouse model of visceral leishmaniasis showed decreased parasite burden and induction of liver cell apoptosis. Collectively, our investigation revealed a key mechanism of how L. donovani exploits TCTP to establish infection within the host.

Designing for empowerment impact in agricultural development projects: Experimental evidence from the Agriculture, Nutrition, and Gender Linkages (ANGeL) project in Bangladesh.

The importance of women's roles for nutrition-sensitive agricultural projects is increasingly recognized, yet little is known about whether such projects improve women's empowerment and gender equality. We study the Agriculture, Nutrition, and Gender Linkages (ANGeL) pilot project, which was implemented as a cluster-randomized controlled trial by the Government of Bangladesh. The project's treatment arms included agricultural training, nutrition behavior change communication (BCC), and gender sensitization trainings delivered to husbands and wives together - with these components combined additively, such that the impact of gender sensitization could be distinguished from that of agriculture and nutrition trainings. Empowerment was measured using the internationally-validated project-level Women's Empowerment in Agriculture Index (pro-WEAI), and attitudes regarding gender roles were elicited from both men and women, to explore potentially gender-transformative impacts. Our study finds that ANGeL increased both women's and men's empowerment, raised the prevalence of households achieving gender parity, and led to small improvements in the gender attitudes of both women and men. We find significant increases in women's empowerment scores and empowerment status from all treatment arms but with no significant differences across these. We find no evidence of unintended impacts on workloads and inconclusive evidence around impacts on intimate partner violence. Our results also suggest some potential benefits of bundling nutrition and gender components with an agricultural development intervention; however, many of these benefits seem to be driven by bundling nutrition with agriculture. While we cannot assess the extent to which including men and women within the same treatment arms contributed to our results, it is plausible that the positive impacts of all treatment arms on women's empowerment outcomes may have arisen from implementation modalities that provided information to both husbands and wives when they were together. The role of engaging men and women jointly in interventions is a promising area for future research.

Social Assistance Programs and Birth Outcomes: A Systematic Review and Assessment of Nutrition and Health Pathways.

BACKGROUND: Poor birth outcomes are an important global public health problem. Social assistance programs that provide cash or in-kind transfers, such as food or vouchers, hold potential to improve birth outcomes but the evidence on their effectiveness has not been reviewed. OBJECTIVES: We systematically reviewed studies that used experimental or quasi-experimental methods to evaluate the impacts of social assistance programs on outcomes in low- and middle-income countries. METHODS: The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system was used to assess the certainty of the evidence for birth weight and neonatal mortality (most common outcomes reported). We summarized the evidence on hypothesized nutrition and health pathways of impact. RESULTS: We included 6 evaluations of 4 different cash transfer programs and 1 evaluation of a community-based participatory learning and action program that provided food and cash transfers. The 4 studies that assessed birth weight impacts found significant (P < 0.05) effects ranging from 31 to 578 g. Out of 3 studies that assessed neonatal mortality impacts, 2 found significant effects ranging from 0.6 to 3.1 deaths/1000 live births. The certainty of the evidence for both outcomes was rated as very low due to several methodological limitations. In terms of potential pathways, some studies documented positive effects on maternal diet, antenatal care (ANC) utilization, and delivery in a health facility. CONCLUSIONS: Better-designed evaluations are needed to strengthen the evidence base on these programs. Evaluation studies should elucidate underlying mechanisms of impact by including outcomes related to maternal diet, ANC seeking, use of skilled delivery, and women's empowerment in nutrition and health domains. Studies should also assess potential unintended negative consequences of social assistance, such as reduced birth spacing and excess pregnancy weight gain.

Cross-disciplinary intersections between public health and economics in intimate partner violence research.

Research on intimate partner violence (IPV) has progressed in the last decade in the fields of public health and economics, with under-explored potential for cross-fertilisation. We examine the theoretical perspectives and methodological approaches that each discipline uses to conceptualise and study IPV and offer a perspective on their relative advantages. Public health takes a broad theoretical perspective anchored in the socio-ecological framework, considering multiple and synergistic drivers of IPV, while economics focuses on bargaining models which highlight individual power and factors that shape this power. These perspectives shape empirical work, with public health examining multi-faceted interventions, risk and mediating factors, while economics focuses on causal modelling of specific economic and institutional factors and economic-based interventions. The disciplines also have differing views on measurement and ethics in primary research. We argue that efforts to understand and address IPV would benefit if the two disciplines collaborated more closely and combined the best traditions of both fields.

Leishmania donovani Targets Host Transcription Factor NRF2 To Activate Antioxidant Enzyme HO-1 and Transcriptional Repressor ATF3 for Establishing Infection.

We showed previously that antioxidant enzyme heme oxygenase 1 (HO-1) is critical for Leishmania survival in visceral leishmaniasis. HO-1 inhibits host oxidative burst and inflammatory cytokine production, leading to parasite persistence. In the present study, screening of reported HO-1 transcription factors revealed that infection upregulated (4.1-fold compared to control [P < 0.001]) nuclear factor erythroid 2 (NFE2)-related factor 2 (NRF2). Silencing of NRF2 reduced both HO-1 expression and parasite survival. Investigation revealed that infection-induced transient reactive oxygen species (ROS) production dissociated NRF2 from its inhibitor KEAP1 and enabled phosphorylation-dependent nuclear translocation. Both NRF2 and HO-1 silencing in infection increased production of proinflammatory cytokines. But the level was greater in NRF2-silenced cells than in HO-1-silenced ones, suggesting the presence of other targets of NRF2. Another stress responsive transcription factor ATF3 is also induced (4.6-fold compared to control [P < 0.001]) by NRF2 during infection. Silencing of ATF3 reduced parasite survival (59.3% decrease compared to control [P < 0.001]) and increased proinflammatory cytokines. Infection-induced ATF3 recruited HDAC1 into the promoter sites of tumor necrosis factor alpha (TNF-α) and interleukin 12b (IL-12b) genes. Resulting deacetylated histones prevented NF-κB promoter binding, thereby reducing transcription of inflammatory cytokines. Administering the NRF2 inhibitor trigonelline hydrochloride to infected BALB/c mice resulted in reduced HO-1 and ATF3 expression, decreased spleen and liver parasite burdens, and increased proinflammatory cytokine levels. These results suggest that Leishmania upregulates NRF2 to activate both HO-1 and ATF3 for disease progression.

PRELIMINARY EXPERIMENTATIONS ON THE IN VITRO REARING OF HEMATOPHAGOUS PIGEON LOUSE HOHORSTIELLA LATA (AMBLYCERA: PHTHIRAPTERA: INSECTA).

Rearing hematophagous amblyceran lice in vitro is a challenging task. The hematophagous nature and active habits of amblycerans are distinct hurdles to in vitro rearing. The literature indicates only limited success in rearing the hematophagous amblyceran avian louse. Herein we report on the results of in vitro experimentation on an amblyceran pigeon louse, Hohorstiella lata. The incubation period of eggs was 5.47 ± 0.52 days. The durations of first, second, and third nymphal instars were 5.14 ± 0.55, 5.65 ± 0.83, and 6.35 ± 0.82 days, respectively. The average lifespan of adult females (7.45 ± 5.88 days) was higher than adult males (4.61 ± 3.57 days). Adult females laid a lifetime average of 3.73 eggs at a rate of 0.45 eggs/female/day under in vitro conditions (35 ± 1 C, 75-82% relative humidity, feather diet).

Intimate Partner Relationships and Gender Norms in Mali: The Scope of Cash Transfers Targeted to Men to Reduce Intimate Partner Violence.

Mali has implemented the Filets Sociaux (Jigisémèjiri) program that aims to reduce poverty through cash transfers (CTs) to predominantly male heads of household with accompanying measures. This paper reports on a qualitative study of the effects of the program on intimate partner relationships. In-depth interviews were conducted with men and women in monogamous and polygamous households. Findings revealed that the positive aspects of intimate partner relationships were communication and shared values. However, discussions around decision-making revealed male authority with limited influence by women. Physical violence was reported to be caused by tensions and disputes. Whereas sexual violence was contested, some women described sexual force as violence but men and women asserted that compliance in sexual matters by women was expected. Men also asserted control through preventing women from working outside the home. The CTs were managed by the husband, with some involvement of wives in decision-making about the use of CTs. CTs were reported to reduce household poverty and improve wellbeing, especially for men. There were reports of the effects of the program on IPV, especially in the reduction of physical violence, its effects on sexual violence and controlling behaviour were reported to be limited. Since women are not the primary recipients of the CT, there is limited effect on women's agency to challenge male authority and control around sexual and financial matters. CTs may be more effective if targeted to women, alongside skill and knowledge strengthening to utilize cash transfers to assert their rights to equality and prevent violence.

Antileishmanial effect of the natural immunomodulator genipin through suppression of host negative regulatory protein UCP2.

OBJECTIVES: To evaluate the antileishmanial efficacy of genipin, which specifically inhibits uncoupling protein 2 (UCP2) that is induced in leishmaniasis to neutralize reactive oxygen species (ROS). METHODS: The effect of genipin was assessed against intracellular parasites in cultured macrophages and in suppressing spleen and liver parasite burdens in a BALB/c mouse model of visceral leishmaniasis by microscopic evaluation of intracellular amastigotes stained with Giemsa. ROS and mitochondrial membrane potential were measured by H2DCFDA- and JC-1-based fluorometric analysis. ELISA was performed for various Th1 and Th2 cytokines in both in vitro and in vivo infected conditions to evaluate the type of immunological responses. The role of UCP2 was assessed by lipofectamine-mediated transfection and overexpression in macrophages and short hairpin RNA-mediated knockdown of UCP2 in infected animals. RESULTS: Genipin reduced the infection-induced UCP2 levels in macrophages, with optimum effect at 100 µM. Genipin reversed parasite-induced ROS suppression and mitochondrial membrane potential disruption. It has no inhibitory effect on promastigote or axenic amastigote forms, but markedly suppressed amastigote multiplication within macrophages, which was reversed by the ROS scavenger N-acetyl cysteine. Genipin administration (30 mg/kg/day) in infected mice showed significant suppression of liver and spleen parasite burdens with an enhanced host-favourable cytokine balance in a ROS-p38 mitogen-activated protein kinase-dependent manner. Co-treatment with genipin plus a sublethal dose of sodium antimony gluconate (SAG50) showed almost a curative reduction in spleen and liver parasite burden. CONCLUSIONS: These results suggest the effectiveness of genipin as a synergistic agent for the front-line antileishmanial drug SAG in circumventing the resistance and toxicity problems associated with its high curative dose.

Randomized controlled trials of multi-sectoral programs: Lessons from development research.

Development is a multi-faceted process; achieving development goals thus requires a multi-sectoral approach. For over two decades, our research group of economists and nutritionists has designed and implemented randomized trials to assess the effectiveness of multisectoral programs in improving nutrition, food security, and other measures of well-being, largely at the request of developing country governments, development partners, and non-governmental organizations. Our approach addresses three perceived pitfalls of RCTs: the "black box" nature of RCTs, limited external validity, and challenges in translation of results to impacts at scale. We address these concerns by identifying and assessing programmatic pathways to impact with quantitative and qualitative methods; studying similar programs implemented by different organizations across various settings; and working closely with implementing partners in the design, research, and dissemination processes to inform adaptation and scale-up of programs and policies.