ABSTRACT
PURPOSE: Over 550 loci have been associated with human pulmonary function in genome-wide association studies (GWAS); however, the causal role of most remains uncertain. Single nucleotide polymorphisms in a disintegrin and metalloprotease domain 19 (ADAM19) are consistently related to pulmonary function in GWAS. Thus, we used a mouse model to investigate the causal link between Adam19 and pulmonary function. METHODS: We created an Adam19 knockout (KO) mouse model and validated the gene targeting using RNA-Seq and RT-qPCR. Mouse body composition was assessed using dual-energy X-ray absorptiometry. Mouse lung function was measured using flexiVent. RESULTS: Contrary to prior publications, the KO was not neonatal lethal. KO mice had lower body weight and shorter tibial length than wild-type (WT) mice. Their body composition revealed lower soft weight, fat weight, and bone mineral content. Adam19 KO had decreased baseline respiratory system elastance, minute work of breathing, tissue damping, tissue elastance, and forced expiratory flow at 50% forced vital capacity but higher FEV0.1 and FVC. Adam19 KO had attenuated tissue damping and tissue elastance in response to methacholine following LPS exposure. Adam19 KO also exhibited attenuated neutrophil extravasation into the airway after LPS administration compared to WT. RNA-Seq analysis of KO and WT lungs identified several differentially expressed genes (Cd300lg, Kpna2, and Pttg1) implicated in lung biology and pathogenesis. Gene set enrichment analysis identified negative enrichment for TNF pathways. CONCLUSION: Our murine findings support a causal role of ADAM19, implicated in human GWAS, in regulating pulmonary function.
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BACKGROUND: Chronic exposure to microorganisms inside homes can impact respiratory health. Few studies have used advanced sequencing methods to examine adult respiratory outcomes, especially continuous measures. We aimed to identify metagenomic profiles in house dust related to the quantitative traits of pulmonary function and airway inflammation in adults. Microbial communities, 1264 species (389 genera), in vacuumed bedroom dust from 779 homes in a US cohort were characterized by whole metagenome shotgun sequencing. We examined two overall microbial diversity measures: richness (the number of individual microbial species) and Shannon index (reflecting both richness and relative abundance). To identify specific differentially abundant genera, we applied the Lasso estimator with high-dimensional inference methods, a novel framework for analyzing microbiome data in relation to continuous traits after accounting for all taxa examined together. RESULTS: Pulmonary function measures (forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio) were not associated with overall dust microbial diversity. However, many individual microbial genera were differentially abundant (p-value < 0.05 controlling for all other microbial taxa examined) in relation to FEV1, FVC, or FEV1/FVC. Similarly, fractional exhaled nitric oxide (FeNO), a marker of airway inflammation, was unrelated to overall microbial diversity but associated with differential abundance for many individual genera. Several genera, including Limosilactobacillus, were associated with a pulmonary function measure and FeNO, while others, including Moraxella to FEV1/FVC and Stenotrophomonas to FeNO, were associated with a single trait. CONCLUSIONS: Using state-of-the-art metagenomic sequencing, we identified specific microorganisms in indoor dust related to pulmonary function and airway inflammation. Some were previously associated with respiratory conditions; others were novel, suggesting specific environmental microbial components contribute to various respiratory outcomes. The methods used are applicable to studying microbiome in relation to other continuous outcomes. Video Abstract.
Subject(s)
Dust , Metagenome , Microbiota , Dust/analysis , Humans , Female , Male , United States , Microbiota/genetics , Middle Aged , Lung/microbiology , Adult , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Forced Expiratory Volume , Agriculture , Respiratory Function Tests , Vital Capacity , Metagenomics/methodsABSTRACT
Chronic Obstructive Pulmonary Disease is a progressive lung disease associated with anxiety, depression, and reduced health-related quality of life. Pulmonary rehabilitation (PR) is a cost-effective and transformative treatment, but 31% of referred patients do not take up their PR appointment. The study aimed to develop user requirements for an intervention to increase PR uptake. A systems approach, the Engineering Better Care framework, was used to develop a system map of the PR pathway, translate evidence-based user needs into user requirements, and validate the user requirements in a stakeholder workshop. Eight user requirements addressed patient and health care practitioner needs to understand what PR entails, understand the benefits of PR and have positive conversations about PR to address patient concerns. The solution-independent user requirements can be applied to the development of any intervention sharing similar goals. The study demonstrates potential in taking a systems approach to more challenges within respiratory medicine.
Subject(s)
Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/rehabilitation , Pulmonary Disease, Chronic Obstructive/psychology , Quality of Life , Patient Acceptance of Health CareABSTRACT
Background: To address inequitable diagnostic access and improve time-to-treatment for First Nations peoples, molecular point-of-care (POC) testing for chlamydia, gonorrhoea and trichomonas was integrated into 49 primary care clinics across Australia. We conducted an observational evaluation to determine clinical effectiveness and analytical quality of POC testing delivered through this national program. Methods: We evaluated (i) implementation by measuring trends in mean monthly POC testing; ii) clinical effectiveness by comparing proportions of positive patients treated by historical control/intervention period and by test type, and calculated infectious days averted; (iii) analytical quality by calculating result concordance by test type, and proportion of unsuccessful POC tests. Findings: Between 2016 and 2022, 46,153 POC tests were performed; an increasing mean monthly testing trend was observed in the first four years (p < 0.0001). A greater proportion of chlamydia/gonorrhoea positives were treated in intervention compared with historical control periods (≤2 days: 37% vs 22% [RR 1.68; 95% CI 1.12, 2.53]; ≤7 days: 48% vs 30% [RR 1.6; 95% CI 1.10, 2.33]; ≤120 days: 79% vs 54% [RR 1.46; 95% CI 1.10, 1.95]); similarly for trichomonas positives and by test type. POC testing for chlamydia, gonorrhoea and trichomonas averted 4930, 5620 and 7075 infectious days, respectively. Results concordance was high [99.0% (chlamydia), 99.3% (gonorrhoea) and 98.9% (trichomonas)]; unsuccessful POC test proportion was 1.8% for chlamydia/gonorrhoea and 2.1% for trichomonas. Interpretation: Molecular POC testing was successfully integrated into primary care settings as part of a routinely implemented program achieving significant clinical benefits with high analytical quality. In addition to the individual health benefits of earlier treatment, fewer infective days could contribute to reduced transmissions in First Nations communities. Funding: This work was supported by an Australian National Health and Medical Research Council Partnership Grant (APP1092503), the Australian Government Department of Health, Western Australia and Queensland Departments of Health.
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Background Disproportionate rates of sexually transmissible infections (STIs) among Aboriginal and Torres Strait Islander young people are often attributed to risk-taking behaviours, but research rarely conducts direct comparison with their non-Indigenous peers to address this negative discourse. Methods 'Let's Talk About It 2019' was a cross-sectional online survey of South Australians (16-29 years). It prioritised recruitment of Aboriginal and Torres Strait Islander respondents to compare behaviours with non-Indigenous peers using multivariable Poisson regression models. Results Aboriginal and Torres Strait Islander (n =231) and non-Indigenous (n =2062) respondents reported similar condom use (40% vs 43%, P =0.477) and sexual debut median ages (16 years vs 17 years). Higher proportions of Aboriginal and/or Torres Strait Islander respondents reported a recent health check (48% vs 38%, P =0.002), STIs (60% vs 49%, P P =0.006) testing, STI diagnosis (29% vs 21%, P =0.042), and intoxication during last sex (30% vs 18%, P Conclusions Behaviours associated with STI transmission were mostly similar among Aboriginal and Torres Strait Islander and non-Indigenous respondents. Higher STI/HIV testing among Aboriginal and Torres Strait Islander respondents suggests effectiveness of targeted programs. Interventions targeting substance use and condom use among all young people are needed. Future interventions need to focus beyond behaviours and explore social determinants of health and sexual networks as contributors to disproportionate STI rates.
Subject(s)
Sexual Behavior , Sexually Transmitted Diseases , Adolescent , Adult , Female , Humans , Male , Young Adult , Australasian People , Australian Aboriginal and Torres Strait Islander Peoples , Cross-Sectional Studies , Risk-Taking , Sexual Behavior/statistics & numerical data , Sexual Behavior/ethnology , Sexually Transmitted Diseases/ethnology , Sexually Transmitted Diseases/diagnosis , South Australia , Surveys and QuestionnairesABSTRACT
The transformation from a fibroblast mesenchymal cell state to an epithelial-like state is critical for induced pluripotent stem cell (iPSC) reprogramming. In this report, we describe studies with PFI-3, a small-molecule inhibitor that specifically targets the bromodomains of SMARCA2/4 and PBRM1 subunits of SWI/SNF complex, as an enhancer of iPSC reprogramming efficiency. Our findings reveal that PFI-3 induces cellular plasticity in multiple human dermal fibroblasts, leading to a mesenchymal-epithelial transition during iPSC formation. This transition is characterized by the upregulation of E-cadherin expression, a key protein involved in epithelial cell adhesion. Additionally, we identified COL11A1 as a reprogramming barrier and demonstrated COL11A1 knockdown increased reprogramming efficiency. Notably, we found that PFI-3 significantly reduced the expression of numerous extracellular matrix (ECM) genes, particularly those involved in collagen assembly. Our research provides key insights into the early stages of iPSC reprogramming, highlighting the crucial role of ECM changes and cellular plasticity in this process.
Subject(s)
Cell Plasticity , Cellular Reprogramming , Extracellular Matrix , Induced Pluripotent Stem Cells , Transcription Factors , Humans , Induced Pluripotent Stem Cells/metabolism , Induced Pluripotent Stem Cells/cytology , Cellular Reprogramming/genetics , Cellular Reprogramming/drug effects , Extracellular Matrix/metabolism , Transcription Factors/metabolism , Transcription Factors/genetics , Cell Plasticity/genetics , Cell Plasticity/drug effects , Fibroblasts/metabolism , Fibroblasts/cytology , Gene Expression Regulation/drug effects , Epithelial-Mesenchymal Transition/genetics , Epithelial-Mesenchymal Transition/drug effectsABSTRACT
Herpes simplex virus type 1 (HSV-1), a neurotropic DNA virus, establishes latency in neural tissues, with reactivation causing severe consequences like encephalitis. Emerging evidence links HSV-1 infection to chronic neuroinflammation and neurodegenerative diseases. Microglia, the central nervous system's (CNS) immune sentinels, express diverse receptors, including α7 nicotinic acetylcholine receptors (α7 nAChRs), critical for immune regulation. Recent studies suggest α7 nAChR activation protects against viral infections. Here, we show that α7 nAChR agonists, choline and PNU-282987, significantly inhibit HSV-1 replication in microglial BV2 cells. Notably, this inhibition is independent of the traditional ionotropic nAChR signaling pathway. mRNA profiling revealed that choline stimulates the expression of antiviral factors, IL-1ß and Nos2, and down-regulates the apoptosis genes and type A Lamins in BV2 cells. These findings suggest a novel mechanism by which microglial α7 nAChRs restrict viral infections by regulating innate immune responses.
Subject(s)
Choline , Herpesvirus 1, Human , Microglia , Virus Replication , alpha7 Nicotinic Acetylcholine Receptor , alpha7 Nicotinic Acetylcholine Receptor/metabolism , alpha7 Nicotinic Acetylcholine Receptor/genetics , Microglia/virology , Microglia/drug effects , Microglia/metabolism , Herpesvirus 1, Human/physiology , Herpesvirus 1, Human/drug effects , Animals , Cell Line , Mice , Virus Replication/drug effects , Choline/pharmacology , Choline/metabolism , Bridged Bicyclo Compounds/pharmacology , Benzamides/pharmacology , Immunity, Innate , Herpes Simplex/virology , Herpes Simplex/metabolism , Interleukin-1beta/metabolism , Signal Transduction/drug effects , Apoptosis/drug effects , Antiviral Agents/pharmacology , Nicotinic Agonists/pharmacology , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide Synthase Type II/geneticsABSTRACT
BACKGROUND: Indigenous adolescents access primary health care services at lower rates, despite their greater health needs and experience of disadvantage. This systematic review identifies the enablers and barriers to primary health care access for Indigenous adolescents to inform service and policy improvements. METHODS: We systematically searched databases for publications reporting enablers or barriers to primary health care access for Indigenous adolescents from the perspective of adolescents, their parents and health care providers, and included studies focused on Indigenous adolescents aged 10-24 years from Australia, Canada, New Zealand, and United States of America. Results were analyzed against the WHO Global standards for quality health-care services for adolescents. An additional ninth standard was added which focused on cultural safety. RESULTS: A total of 41 studies were included. More barriers were identified than enablers, and against the WHO Global standards most enablers and barriers related to supply factors - providers' competencies, appropriate package of services, and cultural safety. Providers who built trust, respect, and relationships; appropriate package of service; and culturally safe environments and care were enablers to care reported by adolescents, and health care providers and parents. Embarrassment, shame, or fear; a lack of culturally appropriate services; and privacy and confidentiality were common barriers identified by both adolescent and health care providers and parents. Cultural safety was identified as a key issue among Indigenous adolescents. Enablers and barriers related to cultural safety included culturally appropriate services, culturally safe environment and care, traditional and cultural practices, cultural protocols, Indigenous health care providers, cultural training for health care providers, and colonization, intergenerational trauma, and racism. Nine recommendations were identified which aim to address the enablers and barriers associated with primary health care access for Indigenous adolescents. CONCLUSION: This review provides important evidence to inform how services, organizations and governments can create accessible primary health care services that specifically meet the needs of Indigenous adolescents. We identify nine recommendations for improving the accessibility of primary health care services for Indigenous adolescents.
Subject(s)
Health Services Accessibility , Health Services, Indigenous , Indigenous Peoples , Primary Health Care , Adolescent , Humans , Australia , Canada , New Zealand , Primary Health Care/standards , United StatesABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection involves an initial viral infection phase followed by a host-response phase that includes an eicosanoid and cytokine storm, lung inflammation and respiratory failure. While vaccination and early anti-viral therapies are effective in preventing or limiting the pathogenic host response, this latter phase is poorly understood with no highly effective treatment options. Inhibitors of soluble epoxide hydrolase (sEH) increase levels of anti-inflammatory molecules called epoxyeicosatrienoic acids (EETs). This study aimed to investigate the impact of sEH inhibition on the host response to SARS-CoV-2 infection in a mouse model with human angiotensin-converting enzyme 2 (ACE2) expression. Mice were infected with SARS-CoV-2 and treated with either vehicle or the sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU). At day 5 post-infection, SARS-CoV-2 induced weight loss, clinical signs, a cytokine storm, an eicosanoid storm, and severe lung inflammation with ~50% mortality on days 6-8 post-infection. SARS-CoV-2 infection induced lung expression of phospholipase A2 (PLA2), cyclooxygenase (COX) and lipoxygenase (LOX) pathway genes, while suppressing expression of most cytochrome P450 genes. Treatment with the sEH inhibitor TPPU delayed weight loss but did not alter clinical signs, lung cytokine expression or overall survival of infected mice. Interestingly, TPPU treatment significantly reversed the eicosanoid storm and attenuated viral-induced elevation of 39 fatty acids and oxylipins from COX, LOX and P450 pathways, which suggests the effects at the level of PLA2 activation. The suppression of the eicosanoid storm by TPPU without corresponding changes in lung cytokines, lung inflammation or mortality reveals a surprising dissociation between systemic oxylipin and cytokine signaling pathways during SARS-CoV-2 infection and suggests that the cytokine storm is primarily responsible for morbidity and mortality in this animal model.
Subject(s)
COVID-19 Drug Treatment , COVID-19 , Cytokine Release Syndrome , Eicosanoids , Epoxide Hydrolases , SARS-CoV-2 , Animals , Mice , Eicosanoids/metabolism , COVID-19/immunology , COVID-19/virology , COVID-19/metabolism , SARS-CoV-2/drug effects , Epoxide Hydrolases/antagonists & inhibitors , Epoxide Hydrolases/metabolism , Cytokine Release Syndrome/drug therapy , Piperidines/pharmacology , Piperidines/therapeutic use , Cytokines/metabolism , Humans , Lung/virology , Lung/metabolism , Lung/pathology , Lung/drug effects , Angiotensin-Converting Enzyme 2/metabolism , Disease Models, Animal , Phenylurea Compounds/pharmacology , Phenylurea Compounds/therapeutic use , FemaleABSTRACT
INTRODUCTION: The effectiveness of antibiotics for treating gonococcal infections is compromised due to escalating antibiotic resistance; and the development of an effective gonococcal vaccine has been challenging. Emerging evidence suggests that the licensed meningococcal B (MenB) vaccine, 4CMenB is effective against gonococcal infections due to cross-reacting antibodies and 95% genetic homology between the two bacteria, Neisseria meningitidis and Neisseria gonorrhoeae, that cause the diseases. This project aims to undertake epidemiological and genomic surveillance to evaluate the long-term protection of the 4CMenB vaccine against gonococcal infections in the Northern Territory (NT) and South Australia (SA), and to determine the potential benefit of a booster vaccine doses to provide longer-term protection against gonococcal infections. METHODS AND ANALYSES: This observational study will provide long-term evaluation results of the effectiveness of the 4CMenB vaccine against gonococcal infections at 4-7 years post 4CMenB programme implementation. Routine notifiable disease notifications will be the basis for assessing the impact of the vaccine on gonococcal infections. Pathology laboratories will provide data on the number and percentage of N. gonorrhoeae positive tests relative to all tests administered and will coordinate molecular sequencing for isolates. Genome sequencing results will be provided by SA Pathology and Territory Pathology/New South Wales Health Pathology, and linked with notification data by SA Health and NT Health. There are limitations in observational studies including the potential for confounding. Confounders will be analysed separately for each outcome/comparison. ETHICS AND DISSEMINATION: The protocol and all study documents have been reviewed and approved by the SA Department for Health and Well-being Human Research Ethics Committee (HREC/2022/HRE00308), and the evaluation will commence in the NT on receipt of approval from the NT Health and Menzies School of Health Research Human Research Ethics Committee. Results will be published in peer-reviewed journals and presented at scientific meetings and public forums.
Subject(s)
Gonorrhea , Meningococcal Vaccines , Neisseria gonorrhoeae , Humans , Gonorrhea/prevention & control , Gonorrhea/epidemiology , Northern Territory/epidemiology , Meningococcal Vaccines/administration & dosage , Meningococcal Vaccines/therapeutic use , Neisseria gonorrhoeae/immunology , South Australia/epidemiology , Observational Studies as Topic , FemaleABSTRACT
The 26S proteasome is the major protein degradation machinery in cells. Cancer cells use the proteasome to modulate gene expression networks that promote tumor growth. Proteasome inhibitors have emerged as effective cancer therapeutics, but how they work mechanistically remains unclear. Here, using integrative genomic analysis, we discovered unexpected reprogramming of the chromatin landscape and RNA polymerase II (RNAPII) transcription initiation in breast cancer cells treated with the proteasome inhibitor MG132. The cells acquired dynamic changes in chromatin accessibility at specific genomic loci termed differentially open chromatin regions (DOCR). DOCRs with decreased accessibility were promoter proximal and exhibited unique chromatin architecture associated with divergent RNAPII transcription. Conversely, DOCRs with increased accessibility were primarily distal to transcription start sites and enriched in oncogenic superenhancers predominantly accessible in non-basal breast tumor subtypes. These findings describe the mechanisms by which the proteasome modulates the expression of gene networks intrinsic to breast cancer biology. SIGNIFICANCE: Our study provides a strong basis for understanding the mechanisms by which proteasome inhibitors exert anticancer effects. We find open chromatin regions that change during proteasome inhibition, are typically accessible in non-basal breast cancers.
Subject(s)
Chromatin , Neoplasms , Chromatin/genetics , Proteasome Endopeptidase Complex/genetics , Proteasome Inhibitors/pharmacology , Proteolysis , GenomicsABSTRACT
Criollo cattle, the descendants of animals brought by Iberian colonists to the Americas, have been the subject of natural and human-mediated selection in novel tropical agroecological zones for centuries. Consequently, these breeds have evolved distinct characteristics such as resistance to diseases and exceptional heat tolerance. In addition to European taurine (Bos taurus) ancestry, it has been proposed that gene flow from African taurine and Asian indicine (Bos indicus) cattle has shaped the ancestry of Criollo cattle. In this study, we analysed Criollo breeds from Colombia and Venezuela using whole-genome sequencing (WGS) and single-nucleotide polymorphism (SNP) array data to examine population structure and admixture at high resolution. Analysis of genetic structure and ancestry components provided evidence for African taurine and Asian indicine admixture in Criollo cattle. In addition, using WGS data, we detected selection signatures associated with a myriad of adaptive traits, revealing genes linked to thermotolerance, reproduction, fertility, immunity and distinct coat and skin coloration traits. This study underscores the remarkable adaptability of Criollo cattle and highlights the genetic richness and potential of these breeds in the face of climate change, habitat flux and disease challenges. Further research is warranted to leverage these findings for more effective and sustainable cattle breeding programmes.
ABSTRACT
Purpose: Over 550 loci have been associated with human pulmonary function in genome-wide association studies (GWAS); however, the causal role of most remains uncertain. Single nucleotide polymorphisms in a disintegrin and metalloprotease domain 19 (ADAM19) are consistently related to pulmonary function in GWAS. Thus, we used a mouse model to investigate the causal link between Adam19 and pulmonary function. Methods: We created an Adam19 knockout (KO) mouse model and validated the gene targeting using RNA-Seq and RT-qPCR. Contrary to prior publications, the KO was not neonatal lethal. Thus, we phenotyped the Adam19 KO. Results: KO mice had lower body weight and shorter tibial length than wild type (WT). Dual-energy X-ray Absorptiometry indicated lower soft weight, fat weight, and bone mineral content in KO mice. In lung function analyses using flexiVent, compared to WT, Adam19 KO had decreased baseline respiratory system elastance, minute work of breathing, tissue damping, tissue elastance, and forced expiratory flow at 50% forced vital capacity but higher FEV0.1 and FVC. Adam19 KO had attenuated tissue damping and tissue elastance in response to methacholine following LPS exposure. Adam19 KO also exhibited attenuated neutrophil extravasation into the airway after LPS administration compared to WT. RNA-Seq analysis of KO and WT lungs identified several differentially expressed genes (Cd300lg, Kpna2, and Pttg1) implicated in lung biology and pathogenesis. Gene set enrichment analysis identified negative enrichment for TNF pathways. Conclusion: Our murine findings support a causal role of ADAM19, implicated in human GWAS, in regulating pulmonary function.
ABSTRACT
Globally, there is a growing acknowledgment of Indigenous Peoples' rights to control data related to their communities. This is seen in the development of Indigenous Data Governance standards. As health data collection increases, it's crucial to apply these standards in research involving Indigenous communities. Our study, therefore, aims to systematically review research using routinely collected health data of Indigenous Peoples, understanding the Indigenous Data Governance approaches and the associated advantages and challenges. We searched electronic databases for studies from 2013 to 2022, resulting in 85 selected articles. Of these, 65 (77%) involved Indigenous Peoples in the research, and 60 (71%) were authored by Indigenous individuals or organisations. While most studies (93%) provided ethical approval details, only 18 (21%) described Indigenous guiding principles, 35 (41%) reported on data sovereignty, and 28 (33%) addressed consent. This highlights the increasing focus on Indigenous Data Governance in utilising health data. Leveraging existing data sources in line with Indigenous data governance principles is vital for better understanding Indigenous health outcomes.
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Cell fate decisions are achieved with gene expression changes driven by lineage-specific transcription factors (TFs). These TFs depend on chromatin remodelers including the Brahma-related gene 1 (BRG1)-associated factor (BAF) complex to activate target genes. BAF complex subunits are essential for development and frequently mutated in cancer. Thus, interrogating how BAF complexes contribute to cell fate decisions is critical for human health. We examined the requirement for the catalytic BAF subunit BRG1 in neural progenitor cell (NPC) specification from human embryonic stem cells. During the earliest stages of differentiation, BRG1 was required to establish chromatin accessibility at neuroectoderm-specific enhancers. Depletion of BRG1 dorsalized NPCs and promoted precocious neural crest specification and enhanced neuronal differentiation. These findings demonstrate that BRG1 mediates NPC specification by ensuring proper expression of lineage-specific TFs and appropriate activation of their transcriptional programs.
Subject(s)
Chromatin , Neural Plate , Humans , Chromatin/genetics , DNA Helicases/genetics , DNA Helicases/metabolism , Neural Plate/metabolism , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Transcription Factors/metabolismABSTRACT
BACKGROUND: There is increasing recognition of the importance of the preconception period for addressing reproductive and intergenerational health inequities and supporting improved maternal and child health outcomes. This study aimed to understand the extent and type of evidence that exists in relation to preconception health for Indigenous peoples living in high-income countries with similar experiences of colonisation, namely, Australia, New Zealand, Canada, and the United States. METHODS: This review was conducted as per the JBI methodology and PRISMA Extension for Scoping Reviews. A comprehensive search of PubMed, CINAHL [EBSCO], Ovid Embase, Scopus, and the Wiley Cochrane Library was conducted using keywords and index terms. We included research in English published between January 2010 and June 2023 on quantitative and qualitative primary studies. Data were extracted using a standardised tool, and the analysis included quantitative descriptions and qualitative content analysis. RESULTS: We identified 360 potential studies and included 57 articles in the review. Most studies were from the United States (n = 36, 63.2%) and Australia (n = 13, 22.8%), and they commonly reported associations between preconception health risk factors and maternal or child health outcomes (n = 27, 48.2%) or described the development, implementation, or evaluation of preconception health interventions (n = 26, 46.4%). Common preconception health areas were pre-pregnancy body mass index or weight (n = 34), alcohol (n = 16), diet (n = 14), physical activity (n = 12), and diabetes (n = 11). Most studies focused exclusively on women (n = 46, 80.7%), and very few included men (n = 3, 5.3%). The study populations were mostly urban and rural (n = 25, 43.9%) or rural only (n = 14, 24.6%); however, the geographical remoteness was often unclear (n = 14, 24.6%). CONCLUSIONS: While there was some research relating to the preconception health of Indigenous peoples, this review identified considerable research gaps. There is a need for dedicated research into preconception health risk factors and reproductive health outcomes, attitudes and awareness of preconception health, and preconception health interventions for Indigenous peoples.
Subject(s)
Indigenous Peoples , Preconception Care , Humans , Australia , United States , Canada , Female , New Zealand , Reproductive Health , PregnancyABSTRACT
BACKGROUND: Hepatitis C (HCV) is highly prevalent in First Nations communities globally. Barriers in the uptake of testing and treatment create challenges to realise elimination of HCV in these communities. In efforts to reduce barriers to testing and treatment, the SCALE-C study implemented an HCV test-and-treat intervention integrating point-of-care HCV testing and FibroScan®. SCALE-C was carried out at four Aboriginal Community Controlled Health Services (ACCHS; renowned for providing culturally safe care) in four regional towns in Australia. This qualitative analysis sought to understand healthcare provider and patient perceptions of acceptability of a community-based HCV test-and-treat intervention within ACCHS. METHODS: Semi-structured interviews were undertaken with 23 patient participants and 14 healthcare personnel (including Aboriginal Health Workers/Practitioners, nurses, general practitioners, and practice managers) from across the four ACCHS involved in SCALE-C. A coding framework was developed among study authors and informed by Sekhon's Theoretical Framework of Acceptability. RESULTS: The SCALE-C intervention enabled opportunities for healthcare providers to listen to patients, and for patients to feel heard (affective attitude). HCV testing was opportunistic and often occurred outside of the allocated SCALE-C clinical hours (burden). For patients, HCV testing within SCALE-C was viewed as a moral responsibility and ensured protection of self and others (ethicality). For personnel, SCALE-C (including following up visits) was regarded as an opportunity to engage with patients especially those with complex health needs which may be unrelated to HCV risk factors (ethicality). Patients and personnel widely regarded the SCALE-C intervention to be effective, and the test-and-treat model was preferable for both patients and personnel. CONCLUSION: The SCALE-C intervention was broadly perceived to be acceptable among both healthcare providers and patients within ACCHS. Whilst the prioritisation of HCV was viewed as increasing patient engagement, it was also regarded as an opportunity for addressing other healthcare needs within Aboriginal communities. HCV test-and-treat models of care delivered by ACCHS simplify the HCV care pathway and ensure all HCV care is provided in a culturally safe setting (e.g., patients did not need to attend external services such as pathology).