Strong Born-A First of Its Kind National FASD Prevention Campaign in Australia Led by the National Aboriginal Community Controlled Health Organisation (NACCHO) in Collaboration with the Aboriginal Community Controlled Health Organisations (ACCHOs).

The Strong Born Campaign (2022-2025) was launched by the National Aboriginal Community Controlled Health Organisation (NACCHO) in 2023. Strong Born is the first of its kind national Aboriginal and Torres Strait Islander health promotion campaign to address Fetal Alcohol Spectrum Disorder (FASD) within Australia. Strong Born was developed to address a longstanding, significant gap in health promotion and sector knowledge on FASD, a lifelong disability that can result from alcohol use during pregnancy. Utilizing a strengths-based and culturally sound approach, NACCHO worked closely with the Aboriginal Community Controlled Health Organisations (ACCHOs) to develop the campaign through co-design, as described in this paper. Since its inception, the ACCHOs have continually invested in driving change towards improvements in Aboriginal health determinants and health promotion. The Strong Born Campaign developed culturally safe health promotion tool kits designed for the community and health sector staff and also offered communities the opportunity to apply for FASD Communications and Engagement Grants to engage in local campaign promotion. The tool kits have been disseminated to 92 ACCHOs across Australia. This paper describes the development of the Strong Born Campaign and activities following its launch in February 2023 from an Indigenous context within Australia, as described by NACCHO.

ß-Adrenergic modulation of myocardial conduction velocity: Connexins vs. sodium current.

The heart is capable of rapid changes in cardiac output: these are caused in large part by changes in the activity of the autonomic nervous system that alter heart rate, force and time course of contraction. While studies of autonomic control have focussed on heart rate and contractile mechanisms, fewer studies have considered the influence of electrical propagation across the chamber. Conduction velocity (CV) of the action potential (AP) is an important variable, which ensures efficient pumping action of the heart and, along with AP duration, is a determinant of the electrical stability of the myocardium. CV depends on multiple factors, including tissue excitability and intercellular resistance: the latter is controlled by the number and arrangement of gap junctions (GJs) linking adjacent cardiac cells. Whole heart studies (in vivo and in vitro) report variable effects of sympathetic nervous system stimulation on ventricular CV, a major complication in interpretation being the accompanying increase in heart rate. At the cellular level, changes in cardiomyocyte electrophysiology, mediated via ß-adrenoreceptor (ß-AR) activation, alter the AP shape and amplitude but the influence of these effects on the CV is unclear. Alternatively, CV changes may occur via altered GJ conductance, but despite detailed knowledge of the underlying channel protein (connexin), little consensus exists on the extent and time course of the change in GJ conductance induced by AR activation. This review will examine the literature on the modulation of ventricular AP conduction velocity by ß-AR activation in a range of physiological preparations and highlight unresolved issues.

Activity of the estrogen-metabolizing enzyme cytochrome P450 1B1 influences the development of pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a hyperproliferative vascular disorder observed predominantly in women. Estrogen is a potent mitogen in human pulmonary artery smooth muscle cells and contributes to PAH in vivo; however, the mechanisms attributed to this causation remain obscure. Curiously, heightened expression of the estrogen-metabolizing enzyme cytochrome P450 1B1 (CYP1B1) is reported in idiopathic PAH and murine models of PAH. METHODS AND RESULTS: Here, we investigated the putative pathogenic role of CYP1B1 in PAH. Quantitative reverse transcription-polymerase chain reaction, immunoblotting, and in situ analysis revealed that pulmonary CYP1B1 is increased in hypoxic PAH, hypoxic+SU5416 PAH, and human PAH and is highly expressed within the pulmonary vascular wall. PAH was assessed in mice via measurement of right ventricular hypertrophy, pulmonary vascular remodeling, and right ventricular systolic pressure. Hypoxic PAH was attenuated in CYP1B1(-/-) mice, and the potent CYP1B1 inhibitor 2,3',4,5'-tetramethoxystilbene (TMS; 3 mg · kg(-1) · d(-1) IP) significantly attenuated hypoxic PAH and hypoxic+SU5416 PAH in vivo. TMS also abolished estrogen-induced proliferation in human pulmonary artery smooth muscle cells and PAH-pulmonary artery smooth muscle cells. The estrogen metabolite 16α-hydroxyestrone provoked human pulmonary artery smooth muscle cell proliferation, and this mitogenic effect was greatly pronounced in PAH-pulmonary artery smooth muscle cells. ELISA analysis revealed that 16α-hydroxyestrone concentration was elevated in PAH, consistent with CYP1B1 overexpression and activity. Finally, administration of the CYP1B1 metabolite 16α-hydroxyestrone (1.5 mg · kg(-1) · d(-1) IP) caused the development of PAH in mice. CONCLUSIONS: Increased CYP1B1-mediated estrogen metabolism promotes the development of PAH, likely via the formation of mitogens, including 16α-hydroxyestrone. Collectively, this study reveals a possible novel therapeutic target in clinical PAH.