Balancing evidence-informed and user-responsive design: Experience with human-centered design to generate layered economic empowerment and SRH programming in Tanzania, Ethiopia, and Nigeria.

In 2021, the Adolescents 360 (A360) project pursued a human-centered design (HCD) process to layer complementary economic empowerment components on top of its existing sexual and reproductive health (SRH) interventions targeting adolescent girls aged 15 to 19. Given the volume of evidence informing successful approaches for improving economic and empowerment outcomes for adolescents, we pursued an intentionally evidence-informed and gender-intentional design process, while trying to also respond directly to user insights. In this open letter, we share how we utilized and validated the evidence-base while applying the core tenets of HCD (empathy and user insights) to design holistic, layered programming for girls. We describe three overarching categories which depict how we used the existing evidence and new user insights to strengthen our design process. Often the evidence base allowed us to expedite finding a solution that worked for our users. However, at times there was a disconnect between what we knew worked in the evidence base and what our users said they wanted. New insights also allowed us to build a greater understanding of our users' lived experiences where there were existing evidence gaps. We were aided by the engagement of a technical partner, BRAC, who synthesized evidence for our design teams and functioned as an 'on demand' support mechanism as questions and challenges arose. Yet, the volume of information to absorb almost guaranteed that we would miss out on the opportunity to apply certain evidence-based practices. We encourage researchers to consider how to make evidence more easily digestible to practitioners and for the whole community of practice to work together to identify what questions need to be asked to effectively operationalize evidence in a local context.

Effects of ACTH, dexamethasone, and adrenalectomy on 11beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) gene expression in the rat central nervous system.

Using a highly sensitive quantitative RT-PCR method for the measurement of CYP11B1 (11beta-hydroxylase) and CYP11B2 (aldosterone synthase) mRNAs, we previously demonstrated that CYP11B2 expression in the central nervous system (CNS) is subject to regulation by dietary sodium. We have now quantified the expression of these genes in the CNS of male Wistar Kyoto (WKY) rats in response to systemic ACTH infusion, dexamethasone infusion, and to adrenalectomy. CYP11B1 and CYP11B2 mRNA levels were measured in total RNA isolated from the adrenal gland and discrete brain regions using real-time quantitative RT-PCR. ACTH infusion (40 ng/day for 7 days, N=8) significantly increased CYP11B1 mRNA in the adrenal gland, hypothalamus, and cerebral cortex compared with animals infused with vehicle only. ACTH infusion decreased adrenal CYP11B2 expression but increased expression in all of the CNS regions except the cortex. Dexamethasone (10 microg/day for 7 days, N=8) reduced adrenal CYP11B1 mRNA compared with control animals but had no significant effect on either gene's expression in the CNS. Adrenalectomy (N=6 per group) significantly increased CYP11B1 expression in the hippocampus and hypothalamus and raised CYP11B2 expression in the cerebellum relative to sham-operated animals. This study confirms the transcription of CYP11B1 and CYP11B2 throughout the CNS and demonstrates that gene transcription is subject to differential regulation by ACTH and circulating corticosteroid levels.

A polygenic model of the metabolic syndrome with reduced circulating and intra-adipose glucocorticoid action.

Despite major advances in understanding monogenic causes of morbid obesity, the complex genetic and environmental etiology of idiopathic metabolic syndrome remains poorly understood. One hypothesis suggests that similarities between the metabolic disease of plasma glucocorticoid excess (Cushing's syndrome) and idiopathic metabolic syndrome results from increased glucocorticoid reamplification within adipose tissue by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1). Indeed, 11beta-HSD-1 is now a major therapeutic target. Because much supporting evidence for a role of adipose 11beta-HSD-1 comes from transgenic or obese rodents with single-gene mutations, we investigated whether the predicted traits of metabolic syndrome and glucocorticoid metabolism were coassociated in a unique polygenic model of obesity developed by long-term selection for divergent fat mass (Fat and Lean mice with 23 vs. 4% fat as body weight, respectively). Fat mice exhibited an insulin-resistant metabolic syndrome including fatty liver and hypertension. Unexpectedly, Fat mice had a marked intra-adipose (11beta-HSD-1) and plasma glucocorticoid deficiency but higher liver glucocorticoid action. Furthermore, metabolic disease was exacerbated only in Fat mice when challenged with exogenous glucocorticoids or a high-fat diet. Our data suggest that idiopathic metabolic syndrome might associate with such a novel pattern of glucocorticoid action and sensitivity in humans, with implications for tissue-specific therapeutic targeting of 11beta-HSD-1.

Host sharing and host manipulation by larval helminths in shore crabs: cooperation or conflict?

Larval helminths of different species that share the same intermediate host and are transmitted by predation to the same definitive host may cooperate in their attempts to manipulate the behaviour of the intermediate host, while at the same time having conflicts of interests over the use of host resources. A few studies have indicated that intermediate hosts harbouring larval helminths have altered concentrations of neurotransmitters in their nervous system, and thus measuring levels of neurotransmitters in host brains could serve to assess the respective and combined effect of different helminth species on host behaviour. Here, we investigate potential cooperation and conflict among three helminths in two species of crab intermediate hosts. The acanthocephalan Profilicollis spp., the trematode Maritrema sp. and an acuariid nematode, all use Macrophthalmus hirtipes (Ocypodidae) as intermediate host, whereas Profilicollis and Maritrema also use Hemigrapsus crenulatus (Grapsidae). All three helminths mature inside gulls or other shore birds. There was a significant decrease in the mean volume of Profilicollis cystacanths as the intensity of infection by this parasite increased in H. crenulatus, the only host in which this was investigated; however, there was no measurable effect of other helminth species on the size of acanthocephalans, suggesting no interspecific conflict over resource use within crabs. There was, in contrast, evidence of a positive interspecific association between the two most common helminth species: numbers of Profilicollis and Maritrema were positively correlated among crabs, independently of crab size, in M. hirtipes but not H. crenulatus. More importantly, we found that the total number of larval helminths per crab correlated significantly, and negatively, with concentrations of serotonin in crab brains, again only in M. hirtipes; numbers of each parasite species separately did not covary in either crab species with serotonin or dopamine, the other neurotransmitter investigated in this study. The relationship with serotonin appears due mainly to numbers of Profilicollis and Maritrema and not to nematodes. This is the first demonstration of a potentially synergistic manipulation of host behaviour by different helminth species, one that appears host-specific; our results also point toward the neurobiological mechanism underlying this phenomenon.