Health inequities are differences in health between groups of people that are avoidable, unfair and unjust. Achieving equitable health outcomes requires approaches that recognise and account for the differences in levels of advantage between groups. Implementation science, which studies how to translate evidence-based interventions into routine practice, is increasingly recognised as an approach to address health inequities by identifying factors and processes that enable equitable implementation of interventions. This article describes the protocol for a scoping review of the literature relating to the equitable implementation of interventions, focusing on ethnicity-related health inequities. The scoping review aims to identify equity-focused implementation science theories, models and frameworks (TMFs) and to synthesise and analyse the evidence relating to the factors that aid or inhibit equitable implementation of health interventions.

Pregnancy represents a period of remarkable adaptive physiology throughout the body, with many of these important adaptations mediated by changes in gene transcription in the brain. A marked activation of the transcription factor signal transducer and activator of transcription 5 (STAT5) has been described in the brain during pregnancy and likely drives some of these changes. We aimed to investigate the physiological mechanism causing this increase in phosphorylated STAT5 (pSTAT5) during pregnancy. In various tissues, STAT5 is known to be activated by a number of different cytokines, including erythropoietin, growth hormone and prolactin. Because the lactogenic hormones that act through the prolactin receptor (PRLR), prolactin and its closely-related placental analogue placental lactogen, are significantly increased during pregnancy, we hypothesised that this receptor was primarily responsible for the pregnancy-induced increase in pSTAT5 in the brain. By examining temporal changes in plasma prolactin levels and the pattern of pSTAT5 immunoreactivity in the hypothalamus during early pregnancy, we found that the level of pSTAT5 was sensitive to circulating levels of endogenous prolactin. Using a transgenic model to conditionally delete PRLRs from forebrain neurones (Prlrlox/lox /CamK-Cre), we assessed the relative contribution of the PRLR to the up-regulation of pSTAT5 in the brain of pregnant mice. In the absence of PRLRs on most forebrain neurones, a significant reduction in pSTAT5 was observed throughout the hypothalamus and amygdala in late pregnancy, confirming that PRLR is key in mediating this response. The exception to this was the hypothalamic paraventricular nucleus, where only 17% of pSTAT5 immunoreactivity during pregnancy was in PRLR-expressing cells. Taken together, these data indicate that, although there are region-specific mechanisms involved, lactogenic activity through the PRLR is the primary signal activating STAT5 in the brain during pregnancy.

To study the pathological effects of continuous hyperprolactinemia on food intake mechanisms we used female mice that lack dopamine D2 receptors in lactotropes (lacDrd2KO). These mice had lifelong hyperprolactinemia, increased food intake, and gradual development of obesity from 5 to 10 months of age. Ongoing endogenous prolactin signaling in lacDrd2KO mice was evidenced by increased basal phosphorylation of STAT5b in hypothalamic areas related to food intake, such as the arcuate (ARN), dorsomedial (DMN), and ventromedial nuclei. In the ARN of young lacDrd2KO mice there were higher Prlr mRNA levels and in obese 10-month-old lacDrd2KO mice increased expression of the orexigenic genes Neuropeptide Y (Npy) and Agouti-related peptide, compared to controls. Furthermore, Npy expression was increased in the DMN, probably contributing to increased food intake and decreased expression of Uncoupling protein-1 in brown adipose tissue, both events favoring weight gain. Leptin resistance in obese lacD2RKO mice was evidenced by its failure to lower food intake and a dampened response of STAT3 phosphorylation, specifically in the mediobasal hypothalamus. Our results suggest that pathological chronically high prolactin levels, as found in psychiatric treatments or patients with prolactinomas, may impact on specific hypothalamic nuclei altering gene expression, leptin response, and food intake.

During pregnancy, when both food intake and circulating leptin concentrations increase, the brain becomes insensitive to leptin. The mechanism by which central leptin resistance during pregnancy emerges remains poorly understood. We investigated whether structural changes in the blood-brain barrier (BBB) or changes in carrier-mediated transport of leptin into the brain might contribute to pregnancy-induced leptin resistance. Immunohistochemical evaluation of the BBB at the level of the arcuate nucleus and median eminence in virgin, pregnant, and lactating mice was undertaken by labeling for tanycytes (vimentin), tight junction protein (zona occludens-1), and a marker of fenestrated endothelial capillaries (MECA-32). There were no changes in these BBB markers between virgin, pregnant or lactating mice. Transport of iodine 125-labeled leptin from the peripheral circulation into the brain was completely suppressed during pregnancy, however (days 14 through 16), compared with virgin and lactating (days 7 through 11) mice. This was accompanied by a suppression of leptin clearance from the blood in pregnant mice. We also investigated in virgin mice whether competition with other hormones for transport might contribute to suppression of leptin transport into the brain. Although leptin was able to compete with prolactin transport into the brain, prolactin did not compete with leptin transport. These data demonstrate that suppression of the transport of leptin into the brain during pregnancy, in the absence of structural changes in the BBB, is an important contributor to the insensitivity of the hypothalamus to leptin at this time.

Altered physiological states require neuronal adaptation. In late pregnancy and lactation, a sub-population of the mouse hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons alters their behavior to synthesize and release met-enkephalin rather than dopamine. These neurons normally release dopamine to inhibit prolactin secretion and are activated by prolactin in a short-loop feedback manner. In lactation, dopamine synthesis is suppressed in an opioid-dependent (naloxone-reversible) manner, meaning that prolactin secretion is disinhibited. Conditional deletion of the prolactin receptor in neurons reveals that this change in phenotype appears to be driven by prolactin itself, apparently through an alteration in intracellular signaling downstream of the prolactin receptor that favors enkephalin production instead of dopamine. Thus, prolactin effectively facilitates its own secretion, which is essential for lactation and maternal behavior. These studies provide evidence of a physiologically important, reversible alteration in the behavior of a specific population of hypothalamic neurons in the adult brain.

Inequities in implementation contribute to the unequal benefit of health interventions between groups of people with differing levels of advantage in society. Implementation science theories, models and frameworks (TMFs) provide a theoretical basis for understanding the multi-level factors that influence implementation outcomes and are used to guide implementation processes. This study aimed to identify and analyse TMFs that have an equity focus or have been used to implement interventions in populations who experience ethnicity or 'race'-related health inequities.