"I know who I am; the real me, and that will come back." The importance of relational practice in improving outcomes for carers of people with dementia

Effective support to carers of people with dementia can be critical to maintaining quality of life for people with dementia, their families and to sustaining the future of health and care systems. Qualitative interviews were undertaken with 14 carers of people with dementia across Scotland, and the data analysed to identify the outcomes important to the carers. The importance of relationships emerged as the core theme, including relationship with the person with dementia, family members, other carers, and professionals. Although not evident in the literature, the authors noted the concept of self-relationship was important to carers in the context of changing relationships with others. A multi-layered approach to understanding relationships, and an approach to engagement that enables carers to define and express their priorities, is necessary to fit with the relational nature of care

Tackling NCDs: the need to address Alcohol industry interference and policy incoherence across sectors; Comment on 'Towards preventing and managing conflict of interest in nutrition policy?'

Ralston et al highlight the ways that different actors in global nutrition governance conceptualise and frame the role of non-state actors in governance arrangements, including the potential for conflict of interest (COI) to undermine global health efforts. The authors argue that the World Health Organization (WHO) draft tool on managing COI in nutrition policy is an important innovation in global health, but that further research and refinement is needed for operationalising the management of COI with diverse actors in diverse contexts. In this commentary, reflecting on strategic framing and industry interference in policy-making, we argue for the urgent need for states and intergovernmental organisations to prevent alcohol industry interference in the development of national and global alcohol policy. We argue that policy incoherence remains a key barrier, where governments pursue health goals in the health sector while pursuing exports and market liberalisation of health harmful commodities in the trade secto

Improvements to GALA and dbERGE II: databases featuring genomic sequence alignment, annotation and experimental results

We describe improvements to two databases that give access to information on genomic sequence similarities, functional elements in DNA and experimental results that demonstrate those functions. GALA, the database of Genome ALignments and Annotations, is now a set of interlinked relational databases for five vertebrate species, human, chimpanzee, mouse, rat and chicken. For each species, GALA records pairwise and multiple sequence alignments, scores derived from those alignments that reflect the likelihood of being under purifying selection or being a regulatory element, and extensive annotations such as genes, gene expression patterns and transcription factor binding sites. The user interface supports simple and complex queries, including operations such as subtraction and intersections as well as clustering and finding elements in proximity to features. dbERGE II, the database of Experimental Results on Gene Expression, contains experimental data from a variety of functional assays. Both databases are now run on the DB2 database management system. Improved hardware and tuning has reduced response times and increased querying capacity, while simplified query interfaces will help direct new users through the querying process. Links are available at http://www.bx.psu.edu/

Microglial MAC1 receptor and PI3K are essential in mediating β-amyloid peptide-induced microglial activation and subsequent neurotoxicity

<p>Abstract</p> <p>Background</p> <p>β-Amyloid peptide (Aβ) is a major protein in the brain associated with Alzheimer's and Parkinson's diseases. The purpose of this study was to investigate the role of macrophage antigen-1 (MAC1) receptor, an integrin scavenger receptor in microglia, and subsequent signaling events in mediating Aβ-induced neurotoxicity. We have previously reported that NADPH oxidase (PHOX) on microglia and superoxide produced by PHOX are critical for Aβ-induced loss of dopaminergic neurons. However, the upstream signaling pathway of superoxide production remains unclear.</p> <p>Methods</p> <p>For the <it>in vitro </it>study, mesencephalic neuron-glia cultures and microglia-enriched cultures from mice deficient in the MAC1 receptor (MAC1^-/-) and wild type controls were used to investigate the role of MAC1 receptor in Aβ-induced neurotoxicity and the role of phosphoinositide-3 kinase (PI3K) in the signal pathway between MAC1 receptor and PHOX. For the <it>in vivo </it>study, Aβ was injected into the substantia nigra of MAC1^-/-mice and wild type mice to confirm the role of MAC1 receptor.</p> <p>Results</p> <p>We found that Aβ-induced activation of microglia, activation of PHOX, generation of superoxide and other reactive oxygen species, and loss of dopaminergic neurons were decreased in MAC1^-/-cultures compared to MAC1^+/+cultures. In MAC1^-/-mice, dopaminergic neuron loss in response to Aβ injection into the substantia nigra was reduced relative to MAC1^+/+mice. Thus, MAC1 receptor-mediated PHOX activation and increased superoxide production are associated with Aβ-induced neurotoxicity. PI3K activation was one downstream step in MAC1 signaling to PHOX and played an important role in Aβ-induced neurotoxicity. In microglia-enriched cultures from MAC1^-/-mice, Aβ-induced activation of PI3K (phosphorylation of target proteins and PIP₃production) was reduced relative to MAC1^+/+cultures.</p> <p>Conclusions</p> <p>Taken together, our data demonstrate that Aβ activates MAC1 receptor to increase the activity of PI3K, which in turn phosphorylates p47^{<it>phox</it>}, triggers the translocation of cytosolic subunits of PHOX to microglia membrane, increases PHOX activation and the subsequent production of superoxide and causes neurotoxicity.</p

Revisiting Candidacy: What might it offer cancer prevention?

The notion of candidacy emerged three decades ago through Davison and colleagues’ exploration of people’s understanding of the causes of coronary heart disease. Candidacy was a mechanism to estimate one’s own or others risk of disease informed by their lay epidemiology. It could predict who would develop illness or explain why someone succumbed to it. Candidacy’s predictive ability, however, was fallible, and it was from this perspective that the public’s reticence to adhere to prevention messages could be explained, as ultimately anybody could be ‘at-risk’. This work continues to resonate in health research, with over 700 citations of Davison’s Candidacy paper. Less explored however, is the candidacy framework in its entirety in other illness spheres, where prevention efforts could potentially impact health outcomes. This paper revisits the candidacy framework to reconsider it use within prevention. In doing so, candidacy within coronary heart disease, suicide prevention, diabetes, and cancer will be examined, and key components of candidacy and how people negotiate their candidacy within differing disease contexts will be uncovered. The applicability of candidacy to address modifiable breast cancer risk factors or cancer prevention more broadly will be considered, as will the implications for public health policy

New Insights from Seafloor Mapping of a Hawaiian Marine Monument

On 15 June 2006, when U.S. President George W. Bush signed the proclamation creating the Papahānaumokuākea Marine National Monument (PMNM), he probably wasn’t thinking about underwater morphology. To fully understand the coral reefs and marine ecosystems that the monument was created to protect, however, scientists need to have a detailed picture of the seafloor features, home to corals and other species, as well as the geologic history of the area. Thanks to a recent, multi-institution expedition, such a seafloor features that will not only inform conservation efforts but also enable geologists and geophysicists to revise their understanding of Hawaii’s complex geologic past. Specifically, data should help scientists answer fundamental questions about the area’s regional geology. For instance, which seamounts were truly formed because of Hawaiian hotspot volcanism, and which seamounts were not

Thoracic Society of Australia and New Zealand position statement on acute oxygen use in adults : 'swimming between the flags'

Oxygen is a life-saving therapy but, when given inappropriately, may also be hazardous. Therefore, in the acute medical setting, oxygen should only be given as treatment for hypoxaemia and requires appropriate prescription, monitoring and review. This update to the Thoracic Society of Australia and New Zealand (TSANZ) guidance on acute oxygen therapy is a brief and practical resource for all healthcare workers involved with administering oxygen therapy to adults in the acute medical setting. It does not apply to intubated or paediatric patients. Recommendations are made in the following six clinical areas: assessment of hypoxaemia (including use of arterial blood gases); prescription of oxygen; peripheral oxygen saturation targets; delivery, including non-invasive ventilation and humidified high-flow nasal cannulae; the significance of high oxygen requirements; and acute hypercapnic respiratory failure. There are three sections which provide (1) a brief summary, (2) recommendations in detail with practice points and (3) a detailed explanation of the reasoning and evidence behind the recommendations. It is anticipated that these recommendations will be disseminated widely in structured programmes across Australia and New Zealand

Mental health and use of Medicare Benefits Schedule follow-up mental health services by Indigenous people in Australia during the COVID-19 pandemic

BackgroundMental health care has declined during the COVID-19 pandemic as has attendance for preventive mental health health services. This study aimed to investigate trends in all types of mental health service claims identified in an Indigenous-specific health assessment for Indigenous people before and during COVID-19.MethodsWe conducted an analysis of Medicare Benefits Scheme (MBS) mental health service items (Items 81,325 and 81,355), to investigate the trends in all types of mental health service claims specifically intended for Indigenous people of Australia. Data were analysed using descriptive statistics, including the total annual numbers of Indigenous peoples’ mental health service claims cross-tabulated by age groups and gender, between the calendar years 2017–2021. Multivariable Poisson regression modelling was used to determine associations that were statistically significant.ResultsOur results indicate an overall rise in MBS claims for mental health follow-up services during 2019–2020 followed by a decline in 2020–2021. In addition, there was an overall decline in claims for follow-up psychology services across the time period 2019–2021.ConclusionWe found a significant decline in MBS items specific to follow-up mental health services (MBS Items 81,325 and 81,355) for Indigenous people in Australia suggesting a decline in attendance for mental health service follow-up which in turn may indicate a deficit in mental health care during the COVID-19 pandemic, an issue that may lead to poorer mental health outcomes in the future. Further research is needed to understand whether these changes were due to the impact of the COVID-19 pandemic or other factors

Exposure to ambient particulate matter is associated with accelerated functional decline in idiopathic pulmonary fibrosis

BACKGROUND: Idiopathic pulmonary fibrosis (IPF), a progressive disease with an unknown pathogenesis, may be due in part to an abnormal response to injurious stimuli by alveolar epithelial cells. Air pollution and particulate inhalation of matter evoke a wide variety of pulmonary and systemic inflammatory diseases. We therefore hypothesized that increased average ambient particulate matter (PM) concentrations would be associated with an accelerated rate of decline in FVC in IPF. METHODS: We identified a cohort of subjects seen at a single university referral center from 2007 to 2013. Average concentrations of particulate matter < 10 and < 2.5 μg/m3 (PM10 and PM2.5, respectively) were assigned to each patient based on geocoded residential addresses. A linear multivariable mixed-effects model determined the association between the rate of decline in FVC and average PM concentration, controlling for baseline FVC at first measurement and other covariates. RESULTS: One hundred thirty-five subjects were included in the final analysis after exclusion of subjects missing repeated spirometry measurements and those for whom exposure data were not available. There was a significant association between PM10 levels and the rate of decline in FVC during the study period, with each μg/m3 increase in PM10 corresponding with an additional 46 cc/y decline in FVC (P = .008). CONCLUSIONS: Ambient air pollution, as measured by average PM10 concentration, is associated with an increase in the rate of decline of FVC in IPF, suggesting a potential mechanistic role for air pollution in the progression of disease

Genome-Wide ENU Mutagenesis in Combination with High Density SNP Analysis and Exome Sequencing Provides Rapid Identification of Novel Mouse Models of Developmental Disease

BACKGROUND Mice harbouring gene mutations that cause phenotypic abnormalities during organogenesis are invaluable tools for linking gene function to normal development and human disorders. To generate mouse models harbouring novel alleles that are involved in organogenesis we conducted a phenotype-driven, genome-wide mutagenesis screen in mice using the mutagen N-ethyl-N-nitrosourea (ENU). METHODOLOGY/PRINCIPAL FINDINGS ENU was injected into male C57BL/6 mice and the mutations transmitted through the germ-line. ENU-induced mutations were bred to homozygosity and G3 embryos screened at embryonic day (E) 13.5 and E18.5 for abnormalities in limb and craniofacial structures, skin, blood, vasculature, lungs, gut, kidneys, ureters and gonads. From 52 pedigrees screened 15 were detected with anomalies in one or more of the structures/organs screened. Using single nucleotide polymorphism (SNP)-based linkage analysis in conjunction with candidate gene or next-generation sequencing (NGS) we identified novel recessive alleles for Fras1, Ift140 and Lig1. CONCLUSIONS/SIGNIFICANCE In this study we have generated mouse models in which the anomalies closely mimic those seen in human disorders. The association between novel mutant alleles and phenotypes will lead to a better understanding of gene function in normal development and establish how their dysfunction causes human anomalies and disease.This work was enabled by the Australian Phenomics Network and partly supported by funding from the Australian Government’s National Collaborative Research Infrastructure Strategy, a Strategic Grant from the Faculty of Medicine, Nursing and Health Sciences at Monash University, and the Victorian Government’s Operational Infrastructure Support Program. IS acknowledges support through the NH&MRC R. Douglas Wright and ARC Future Fellowship schemes. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript