Living with rheumatic heart disease at the intersection of biomedical and Aboriginal worldviews

Rheumatic heart disease (RHD) significantly impacts the lives of First Nations Australians. Failure to eliminate RHD is in part attributed to healthcare strategies that fail to understand the lived experience of RHD. To rectify this, a PhD study was undertaken in the Northern Territory (NT) of Australia, combining Aboriginal ways of knowing, being and doing with interviews (24 participants from clinical and community settings) and participant observation to privilege Aboriginal voices, including the interpretations and experiences of Aboriginal co-researchers (described in the adjunct article). During analysis, Aboriginal co-researchers identified three interwoven themes: maintaining good feelings; creating clear understanding (from good information); and choosing a good djalkiri (path). These affirm a worldview that prioritises relationships, positive emotions and the wellbeing of family/community. The findings demonstrate the inter-connectedness of knowledge, choice and behaviour that become increasingly complex in stressful and traumatic health, socioeconomic, political, historical and cultural contexts. Not previously heard in the RHD domain, the findings reveal fundamental differences between Aboriginal and biomedical worldviews contributing to the failure of current approaches to communicating health messages. Mitigating this, Aboriginal co-researchers provided targeted recommendations for culturally responsive health encounters, including: communicating to create positive emotions; building trust; and providing family and community data and health messages (rather than individualistic)

Management of incomplete abortions at South African public hospitals

Objective. The objective of this report was to review and describe the management of incomplete abortion by public sector hospitals.Design. A descriptive study in which data were collected prospectively from routine hospital records on all women admitted with incomplete abortion to a stratified random sample of hospitals between 14 and 28 September 1994.Setting. Public sector hospitals in South Africa.Patients. Women with incomplete abortions.Main outcome measures. Length of hospital stay, details of medical management, details of surgical management, determinants of the above.Main results. Data were collected on 803 patients from the 56 participating hospitals. Of these, 767 (95.9%) were in hospital for 1 day or more, and 753 (95.3%) women underwent evacuation of the uterus. Sharp curettage wasthe method employed in 726 (96.9%) and general anaesthesia was used for 601 (88%) of the women requiring uterine evacuation. Antibiotics were prescribed for 396 (49.5%) and blood transfusions were administered to 125 (17%) women. Statistical analysis showed length of stay to be longer in small hospitals (under 500 beds) and when the medical condition was more severe. Antibiotic  usage and blood transfusion were more common with increasing severity and a low haemoglobin level on admission. However, some inappropriate management was identified with regard to both.Main conclusions. It is suggested that uncomplicated incomplete abortion can be more effectively and safely managed using the manual vacuum aspiration technique with sedation/analgesia as an outpatient procedure. Attention should be directed at the introduction of this management routine at all types of hospital and to the ensuring of appropriate management of women with complicated abortion

Predominant Role of Nuclear Versus Membrane Estrogen Receptor α in Arterial Protection: Implications for Estrogen Receptor α Modulation in Cardiovascular Prevention/Safety

BACKGROUND: Although estrogen receptor α (ERα) acts primarily as a transcription factor, it can also elicit membrane-initiated steroid signaling. Pharmacological tools and transgenic mouse models previously highlighted the key role of ERα membrane-initiated steroid signaling in 2 actions of estrogens in the endothelium: increase in NO production and acceleration of reendothelialization. METHODS AND RESULTS: Using mice with ERα mutated at cysteine 451 (ERaC451A), recognized as the key palmitoylation site required for ERα plasma membrane location, and mice with disruption of nuclear actions because of inactivation of activation function 2 (ERaAF20 = ERaAF2°), we sought to fully characterize the respective roles of nuclear membrane-initiated steroid signaling in the arterial protection conferred by ERα. ERaC451A mice were fully responsive to estrogens to prevent atheroma and angiotensin II-induced hypertension as well as to allow flow-mediated arteriolar remodeling. By contrast, ERαAF20 mice were unresponsive to estrogens for these beneficial vascular effects. Accordingly, selective activation of nuclear ERα with estetrol was able to prevent hypertension and to restore flow-mediated arteriolar remodeling. CONCLUSIONS: Altogether, these results reveal an unexpected prominent role of nuclear ERα in the vasculoprotective action of estrogens with major implications in medicine, particularly for selective nuclear ERα agonist, such as estetrol, which is currently under development as a new oral contraceptive and for hormone replacement therapy in menopausal women

Large Burden of Stroke Incidence in People with Cardiac Disease: A Linked Data Cohort Study.

Purpose: People with cardiac disease have 2–4 times greater risk of stroke than the general population. We measured stroke incidence in people with coronary heart disease (CHD), atrial fibrillation (AF) or valvular heart disease (VHD). Methods: We used a person-linked hospitalization/mortality dataset to identify all people hospitalized with CHD, AF or VHD (1985– 2017), and stratified them as pre-existing (hospitalized 1985–2012 and alive at October 31, 2012) or new (first-ever cardiac hospitalization in the five-year study period, 2012–2017). We identified first-ever strokes occurring from 2012 to 2017 in patients aged 20–94 years and calculated age-specific and age-standardized rates (ASR) for each cardiac cohort. Results: Of the 175,560 people in the cohort, most had CHD (69.9%); 16.3% had multiple cardiac conditions. From 2012–17, 5871 first-ever strokes occurred. ASRs were greater in females than males in single and multiple condition cardiac groups, largely driven by rates in females aged ≥75 years, with stroke incidence in this age group being at least 20% greater in females than males in each cardiac subgroup. In females aged 20–54 years, stroke incidence was 4.9-fold greater in those with multiple versus single cardiac conditions. This differential declined with increasing age. Non-fatal stroke incidence was greater than fatal stroke in all age groups except in the 85–94 age group. Incidence rate ratios were up to 2-fold larger in new versus pre-existing cardiac disease. Conclusion: Stroke incidence in people with cardiac disease is substantial, with older females, and younger patients with multiple cardiac conditions, at elevated risk. These patients should be specifically targeted for evidence-based management to minimize the burden of stroke.Keira Robinson, Judith M Katzenellenbogen, Timothy J Kleinig, Joosup Kim, Charley A Budgeon, Amanda G Thrift, Lee Nedkof

Haploinsufficiency of the corepressor of estrogen receptor activity (REA) enhances estrogen receptor function in the mammary gland

Estrogen receptor (ER)-mediated gene expression plays an essential role in mammary gland morphogenesis, function, and carcinogenesis. The repressor of ER activity (REA) is an ER-interactive protein that counterbalances estrogen-induced ER transcriptional activity. Our previous study showed that genetic deletion of both REA alleles resulted in embryonic lethality. This study demonstrates that REA and ERalpha are coexpressed in mammary epithelial cells. REA heterozygous (REA(+/-)) mutant mice exhibit faster mammary ductal elongation in virgin animals, increased lobuloalveolar development during pregnancy, and delayed mammary gland involution after weaning. These morphological phenotypes of REA(+/-) mice are associated with significantly increased cell proliferation and ER transcriptional activities, as indicated by the estrogen response element (ERE)-luciferase reporter in the WT/ERE-Luc and REA(+/-)/ERE-Luc bigenic mice and by the higher expression levels of estrogen-responsive genes such as progesterone receptor and cyclin D1 in the mammary gland. Our analysis also revealed that REA is an important repressor of ER transcriptional activity in the mammary gland under natural, as well as ovariectomized and estrogen-replaced, hormonal conditions. Our results indicate that REA is a physiological modulator of ER function in the mammary gland and that its correct gene dosage is required for maintenance of normal ER activity and normal mammary gland development. Consequently, a reduction or loss of REA function may cause overactivation of ER and increase breast cancer risk in human

The uterine and vascular actions of Estetrol delineate a distinctive profile of Estrogen Receptor alpha modulation, uncoupling nuclear and membrane activation

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Experimental versus predicted affinities for ligand binding to estrogen receptor: Iterative selection and rescoring of docked

The computational determination of binding modes for a ligand into a protein receptor is much more successful than the prediction of relative binding affinities (RBAs) for a set of ligands. Here we consider the binding of a set of 26 synthetic A-CD ligands into the estrogen receptor ERα. We show that the MOE default scoring function (London dG) used to rank the docked poses leads to a negligible correlation with experimental RBAs. However, switching to an energy-based scoring function, using a multiple linear regression to fit experimental RBAs, selecting top-ranked poses and then iteratively repeating this process leads to exponential convergence in 4-7 iterations and a very strong correlation. The method is robust, as shown by various validation tests. This approach may be of general use in improving the quality of predicted binding affinities

Feedback of research results : reflections from a community-based mental health programme

The lack of feedback of research results to research participants, or the lack of reflection on the feedback process where it does occur, is problematic. Some fundamental issues appear to inform the feedback process, these being the approach adopted by the researchers to research and the uses envisaged for the research and feedback. In this paper, we reflect on feedback sessions conducted with research participants and local community in a community-based mental health programme in a rural area of South Africa. The results of a comprehensive needs assessment were discussed in four different meetings. This paper reflects upon, amongst others, practical/logistical issues, attendance and non-attendance, the issue of language, group dynamics, challenges from participants, and social and cultural constructions of knowledge. It is concluded that when feedback of research results is seen as part of an on-going process of programme development and engagement with various stakeholders, it is a potential point of growth on a number of levels.This article was written by Catriona Macleod in affiliation with the Health Systems Development Unit, Department of Community Health, University of the Witwatersrand and the Department of Educational Psychology, University of ZululandFull text available on publisher website: http://journals.sagepub.com/doi/abs/10.1177/00812463980280040

Group A Streptococcus, Acute Rheumatic Fever and Rheumatic Heart Disease: Epidemiology and Clinical Considerations

Early recognition of group A streptococcal pharyngitis and appropriate management with benzathine penicillin using local clinical prediction rules together with validated rapi-strep testing when available should be incorporated in primary health care. A directed approach to the differential diagnosis of acute rheumatic fever now includes the concept of low-risk versus medium-to-high risk populations. Initiation of secondary prophylaxis and the establishment of early medium to long-term care plans is a key aspect of the management of ARF. It is a requirement to identify high-risk individuals with RHD such as those with heart failure, pregnant women, and those with severe disease and multiple valve involvement. As penicillin is the mainstay of primary and secondary prevention, further research into penicillin supply chains, alternate preparations and modes of delivery is required.SCOPUS: re.jinfo:eu-repo/semantics/publishe