Structure of Amyloid Peptide Ribbons Characterized by Electron Microscopy, Atomic Force Microscopy, and Solid-State Nuclear Magnetic Resonance.

Polypeptides often self-assemble to form amyloid fibrils, which contain cross-β structural motifs and are typically 5-15 nm in width and micrometers in length. In many cases, short segments of longer amyloid-forming protein or peptide sequences also form cross-β assemblies but with distinctive ribbon-like morphologies that are characterized by a well-defined thickness (on the order of 5 nm) in one lateral dimension and a variable width (typically 10-100 nm) in the other. Here, we use a novel combination of data from solid-state nuclear magnetic resonance (ssNMR), dark-field transmission electron microscopy (TEM), atomic force microscopy (AFM), and cryogenic electron microscopy (cryoEM) to investigate the structures within amyloid ribbons formed by residues 14-23 and residues 11-25 of the Alzheimer's disease-associated amyloid-β peptide (Aβ and Aβ).

Sampling approaches and geographic coverage in Mayi Kuwayu: the national study of Aboriginal and Torres Strait Islander wellbeing.

Objective: The objective of this paper is to investigate the geographic distribution of participants in Mayi Kuwayu, the National Study of Aboriginal and Torres Strait Islander Wellbeing. The Mayi Kuwayu Study is the largest national longitudinal study of the health and wellbeing of Aboriginal and Torres Strait Islander adults (aged 16 years and over) in Australia. It is an Aboriginal-led and governed Study with embedded community engagement.

Sequence-Specific Fluorescence Turn-On Sensing of RNA by DNA Probes Incorporating the Tricyclic Cytidine Analogue tC.

Sequence-specific fluorescent probes for RNA are widely used in microscopy applications such as fluorescence in situ hybridization and a growing number of newer approaches to live-cell RNA imaging. The sequence specificity of most of these approaches relies on differential hybridization of the probe to the correct target. Competing sequences with only one or two base mismatches are prone to causing off-target recognition.

Kulay Kalingka, a national cohort study of Aboriginal and Torres Strait Islander peoples' cancer experiences: a study protocol.

Introduction: Aboriginal and Torres Strait Islander peoples are the First Peoples of Australia. Since settler colonisation, Aboriginal and Torres Strait Islander peoples have experienced disparities in health outcomes, including cancer, when compared with non-Indigenous Australians, including higher cancer incidence and mortality rates, and lower participation in cancer screening programmes. Data to monitor and improve outcomes are limited.

Estimating population coverage of Tackling Indigenous Smoking teams, a placed-based health intervention in Australia.

Objective: As part of the Tackling Indigenous Smoking (TIS) program, TIS teams provide Aboriginal and Torres Strait Islander-led tobacco control in their geographic area. We aimed to estimate the percentage and number of Aboriginal and Torres Strait Islander peoples living in an area serviced by a TIS team in 2018-19.

Methods: We analysed weighted, representative data from 8,048 Aboriginal and Torres Strait Islander people aged ≥10 years from the 2018-19 National Aboriginal and Torres Strait Islander Health Survey.

Proton pump inhibitors: Understanding the associated risks and benefits of long-term use.

Purpose: Proton pump inhibitors (PPIs) are widely prescribed medications. Various adverse clinical effects of PPIs have been reported in the literature, particularly over the past decade. The purpose of this article is to review published data primarily describing adverse effects associated with PPI use and to help clinicians determine which patients may still benefit from therapy despite safety concerns.

Population-level contribution of interpersonal discrimination to psychological distress among Australian Aboriginal and Torres Strait Islander adults, and to Indigenous-non-Indigenous inequities: cross-sectional analysis of a community-controlled First Nations cohort study.

Background: International and population-specific evidence identifies elevated psychological distress prevalence among those experiencing interpersonal discrimination. We aim to quantify the potential whole-of-population contribution of interpersonal discrimination to psychological distress prevalence and Indigenous-non-Indigenous gaps in Australia.

Methods: We did a cross-sectional analysis of data from Mayi Kuwayu: the National Study of Aboriginal and Torres Strait Islander Wellbeing.

Time-resolved solid state NMR of biomolecular processes with millisecond time resolution.

We review recent efforts to develop and apply an experimental approach to the structural characterization of transient intermediate states in biomolecular processes that involve large changes in molecular conformation or assembly state. This approach depends on solid state nuclear magnetic resonance (ssNMR) measurements that are performed at very low temperatures, typically 25-30 K, with signal enhancements from dynamic nuclear polarization (DNP). This approach also involves novel technology for initiating the process of interest, either by rapid mixing of two solutions or by a rapid inverse temperature jump, and for rapid freezing to trap intermediate states.

Developing Aboriginal and Torres Strait Islander cultural indicators: an overview from Mayi Kuwayu, the National Study of Aboriginal and Torres Strait Islander Wellbeing.

Background: For Aboriginal and Torres Strait Islander peoples, culture is foundational to health and wellbeing. However, its inherent conceptual complexity and diversity across and within different Aboriginal and Torres Strait Islander cultural groups means that it has rarely been explored in depth by epidemiological research. As a result, there are very few measures which adequately represent the heterogeneity and importance of Aboriginal and Torres Strait Islander cultures for health and wellbeing.

Clearing the air: underestimation of youth smoking prevalence associated with proxy-reporting compared to youth self-report.

Background: Smoking remains a leading cause of disease burden globally. Declining youth smoking prevalence is an essential feature of effective tobacco control; however, accurate data are required to assess progress. This study investigates bias in youth smoking prevalence estimates by respondent type (proxy-reported, self-report with parent present, or self-report independently) for Aboriginal and Torres Strait Islander and total populations of Australia.

Measuring Positive Childhood Experiences: Testing the Structural and Predictive Validity of the Health Outcomes From Positive Experiences (HOPE) Framework.

Objective: Positive childhood experiences (PCEs), that occur within secure and nurturing social environments, are fundamental to healthy physical, social-emotional, and cognitive development. However, reliable measures of these experiences are not yet widely available. We used data from the Longitudinal Study of Australian Children (LSAC) to empirically represent and psychometrically evaluate 3 primary domains of PCEs defined within the Health Outcomes from Positive Experiences (HOPE) framework, specifically: 1) nurturing and supportive relationships; 2) safe and protective environments and; 3) constructive social engagement and connectedness.

Tobacco Related Attitudes and Behaviours in Relation to Exposure to the Tackling Indigenous Smoking Program: Evidence from the Mayi Kuwayu Study.

Smoking is the leading contributor to the burden of disease and mortality for Aboriginal and Torres Strait Islander peoples, with an estimated 37% of all Aboriginal and Torres Strait Islander deaths attributed to smoking. The Tackling Indigenous Smoking (TIS) program was implemented to support people to quit smoking, prevent initiation, and reduce exposure to second-hand smoke. Analysis of baseline (2018-2020) data from a large-scale cohort study was conducted to quantify smoking-related attitudes and behaviours among Aboriginal and Torres Strait Islander adults, overall and in relation to exposure to the TIS program.

Markers of chronic disease risk in a cohort of Aboriginal children: findings from the Study of Environment on Aboriginal Resilience and Child Health (SEARCH).

Objective: This study investigated chronic disease risk markers among a cohort of Aboriginal children in New South Wales.

Methods: Distributions of body mass index (BMI), blood lipids and haemoglobin A1c (HbA1c) among Aboriginal children aged 5-<19 years were investigated. Prevalence ratios (PR) were calculated for borderline/high total cholesterol, low-density lipoprotein (LDL) cholesterol and HbA1c, and low high-density lipoprotein (HDL) cholesterol, by age group, sex and BMI.

Risk of severe illness from COVID-19 among Aboriginal and Torres Strait Islander adults: the construct of 'vulnerable populations' obscures the root causes of health inequities.

Objective: To quantify the prevalence of known health-related risk factors for severe COVID-19 illness among Aboriginal and Torres Strait Islander adults, and their relationship with social determinants.

Methods: Weighted cross-sectional analysis of the 2018-19 National Aboriginal and Torres Strait Islander Health Survey; Odds Ratios for cumulative risk count category (0, 1, or ≥2 health-related risk factors) by social factors calculated using ordered logistic regression.

Results: Of the adult population, 42.

Reflection on modern methods: statistical, policy and ethical implications of using age-standardized health indicators to quantify inequities.

Methods for calculating health indicators profoundly influence understanding of and action on population health and inequities. Age-standardization can be useful and is commonly applied to account for differences in age structures when comparing health indicators across groups. Age-standardized rates have well-acknowledged limitations, including that they are relative indices for comparison, and not accurate measures of actual rates where the age structures of groups diverge.

Prevalence of Everyday Discrimination and Relation with Wellbeing among Aboriginal and Torres Strait Islander Adults in Australia.

Discrimination is a fundamental determinant of health and health inequities. However, despite the high prevalence of discrimination exposure, there is limited evidence specific to Indigenous populations on the link between discrimination and health. This study employs a validated measure to quantify experiences of everyday discrimination in a national sample of Aboriginal and Torres Strait Islander (Australia's Indigenous peoples) adults surveyed from 2018 to 2020 (≥16 years, = 8108).

Reliability, validity, and clinical utility of a culturally modified Kessler scale (MK-K5) in the Aboriginal and Torres Strait Islander population.

Background: Aboriginal and Torres Strait Islander peoples are the first people of Australia. Consequences of historic and contemporary settler-colonialism including racism, trauma, grief and loss (of land, culture, spirituality, and freedoms) have led to substantial negative health and wellbeing impacts. The Kessler Psychological Distress Scales are population and individual-level tools designed to measure general psychological health status.

Automated picking of amyloid fibrils from cryo-EM images for helical reconstruction with RELION.

Cryogenic electron microscopy (cryo-EM) is an important tool for determining the molecular structure of proteins and protein assemblies, including helical assemblies such as amyloid fibrils. In reconstruction of amyloid fibril structures from cryo-EM images, an important early step is the selection of fibril locations. This fibril picking step is typically done by hand, a tedious process when thousands of images need to be analyzed.

Tobacco smoking and mortality among Aboriginal and Torres Strait Islander adults in Australia.

Background: Despite generally high smoking prevalences, stemming from colonization, the relationship of smoking to mortality has not been quantified reliably in an Indigenous population. We investigate smoking and mortality among Aboriginal and Torres Strait Islander adults in Australia, where current adult daily smoking prevalence is 40.2%.

Molecular structure of a prevalent amyloid-β fibril polymorph from Alzheimer's disease brain tissue.

Amyloid-β (Aβ) fibrils exhibit self-propagating, molecular-level polymorphisms that may contribute to variations in clinical and pathological characteristics of Alzheimer's disease (AD). We report the molecular structure of a specific fibril polymorph, formed by 40-residue Aβ peptides (Aβ40), that is derived from cortical tissue of an AD patient by seeded fibril growth. The structure is determined from cryogenic electron microscopy (cryoEM) images, supplemented by mass-per-length (MPL) measurements and solid-state NMR (ssNMR) data.

Developing and validating measures of self-reported everyday and healthcare discrimination for Aboriginal and Torres Strait Islander adults.

Background: It is well established that racism is a fundamental contributor to poor health and inequities. There is consistent evidence of high exposure to discrimination among Aboriginal and Torres Strait Islander (Indigenous Australian) peoples, but impacts have not been fully quantified, in part due to limited measurement tools. We aim to validate instruments developed to measure interpersonal discrimination.

Molecular structure and interactions within amyloid-like fibrils formed by a low-complexity protein sequence from FUS.

Protein domains without the usual distribution of amino acids, called low complexity (LC) domains, can be prone to self-assembly into amyloid-like fibrils. Self-assembly of LC domains that are nearly devoid of hydrophobic residues, such as the 214-residue LC domain of the RNA-binding protein FUS, is particularly intriguing from the biophysical perspective and is biomedically relevant due to its occurrence within neurons in amyotrophic lateral sclerosis, frontotemporal dementia, and other neurodegenerative diseases. We report a high-resolution molecular structural model for fibrils formed by the C-terminal half of the FUS LC domain (FUS-LC-C, residues 111-214), based on a density map with 2.

Staying smoke-free: Factors associated with nonsmoking among urban Aboriginal adolescents in the Study of Environment on Aboriginal Resilience and Child Health (SEARCH).

Issue Addressed: To examine the factors associated with preventing regular smoking among Aboriginal adolescents.

Methods: Cross-sectional analysis of data from 106 Aboriginal adolescents aged 12-17 years, and their caregivers, from four Aboriginal Community Controlled Health Services in urban New South Wales, 2008-2012. The relation of individual, social, environmental and cultural factors to having 'never' smoked tobacco regularly was examined using Poisson regression.

Evaluating Impacts of a One Health Approach to Companion Animal Health and Management in a Remote Aboriginal Community in the Northern Territory, Australia.

This study evaluated a community-driven animal health and management program in the remote community of Wadeye, Northern Territory. This evaluation used a pre-post design to assess changes in animal and human health outcomes over a 12-month period of program implementation, from June 2018 to June 2019. The evaluation assessed the program by comparing animal health outcomes before versus one year after program implementation and comparing human health outcomes before versus during the first 12 months of the program.