Food safety: Maximising impact by understanding the food business context

In Australia there are 5.4 million cases of food-borne illness annually which costs the community $1.2 billion per annum (Department of Health and Ageing 2006). As a co-regulator in food safety, local government has a significant interest in ensuring adherence to good food safety practices. This research project involved focus groups or interviews with food business operators and young food handlers to explore their food safety understanding, attitudes, practices and the organisational culture in which they participated. By its nature qualitative research is not intended to provide definitive generalizable findings. Rather the advantage of a small sample size qualitative study is to provide depth rather than breadth. Thus the findings here provide insight into the complexities and nuances of food safety regulation in a manner which a large scale quantitative study could not

Liver function parameters, cholesterol, and phospholipid α-linoleic acid are associated with adipokine levels in overweight and obese adults

Dysregulation of adipose hormones in obesity has been associated with the hastened development of metabolic syndrome and associated chronic disease sequalae including cardiovascular disease and type 2 diabetes mellitus. This study aims to identify common biochemical and anthropometric markers that impact adipose hormones, including adiponectin and leptin. Based on previous literature, it was hypothesized that these would be adversely impacted by liver function parameters, and adiponectin levels would be positively correlated with phospholipid Ω-3 fatty acids. Forty nondiabetic adult subjects (body mass index, ≥25.0 kg/m2) were recruited. Fasting plasma samples were taken to assess adipokine levels, glucose metabolism, electrolytes, liver enzymes, and blood lipids. Basic anthropometric measurements were also recorded. Adiponectin levels were positively correlated with high-density lipoprotein cholesterol and negatively correlated with anthropometric measures, insulin, liver enzymes, triglycerides, and very low-density lipoprotein cholesterol but not body mass index. Conversely, plasma leptin levels were positively correlated with anthropometric measures, C-reactive protein, high-density lipoprotein cholesterol, and plasma phospholipid proportions of Ω-3 α linoleic acid but inversely correlated with creatinine levels. These results support other data regarding correlations between adiponectin and relative adipose distribution. Correlations with specific liver enzymes may indicate that adiponectin levels are tied to fatty acid deposition in the liver; however, liver/kidney damage though further mechanistic clarification is required. Leptin levels were associated with measures of adiposity but not liver enzymes. Each of these variables, along with blood lipids, may serve as potential future therapeutic targets for the prevention and management of obesity and related comorbidities

TbSAP is a novel chromatin protein repressing metacyclic variant surface glycoprotein expression sites in bloodstream form Trypanosoma brucei

The African trypanosome Trypanosoma brucei is a unicellular eukaryote, which relies on a protective variant surface glycoprotein (VSG) coat for survival in the mammalian host. A single trypanosome has >2000 VSG genes and pseudogenes of which only one is expressed from one of ∼15 telomeric bloodstream form expression sites (BESs). Infectious metacyclic trypanosomes present within the tsetse fly vector also express VSG from a separate set of telomeric metacyclic ESs (MESs). All MESs are silenced in bloodstream form T. brucei. As very little is known about how this is mediated, we performed a whole genome RNAi library screen to identify MES repressors. This allowed us to identify a novel SAP domain containing DNA binding protein which we called TbSAP. TbSAP is enriched at the nuclear periphery and binds both MESs and BESs. Knockdown of TbSAP in bloodstream form trypanosomes did not result in cells becoming more 'metacyclic-like'. Instead, there was extensive global upregulation of transcripts including MES VSGs, VSGs within the silent VSG arrays as well as genes immediately downstream of BES promoters. TbSAP therefore appears to be a novel chromatin protein playing an important role in silencing the extensive VSG repertoire of bloodstream form T. brucei

Promoting children\u27s social and emotional wellbeing in childcare centers within low socioeconomic areas: strategies, facilitators and challenges

Althought childcare centres have a vital role to play in the social and emotional development of children, the strategies used to promote children’s wellbeing in such settings are not well researched. This study aimed to identify the strategies, facilitators and key challenges for promoting children’s social and emotional wellbeing as reported by childcare directors and workers during semi-structured interviews. They reported mainly informal strategies with few formalised policies, curricula or strategies. Staff reported frequent difficulties communicating with parents and/or children due to many families speaking little or no English. Lack of staff training and inadequate resources for activities were other key challenges they identified. Perceived facilitators included staff having strong relationships with each other and sharing a common philosophy, as well as having an open door policy for parents. Systematic development of skills to promote children’s social and emotional wellbeing could help leverage childcare staff’s potential to promote children’s wellbeing during a crucial stage of child development

Longitudinal grey and white matter changes in frontotemporal dementia and Alzheimer's disease

Behavioural variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) dementia are characterised by progressive brain atrophy. Longitudinal MRI volumetry may help to characterise ongoing structural degeneration and support the differential diagnosis of dementia subtypes. Automated, observer-independent atlas-based MRI volumetry was applied to analyse 102 MRI data sets from 15 bvFTD, 14 AD, and 10 healthy elderly control participants with consecutive scans over at least 12 months. Anatomically defined targets were chosen a priori as brain structures of interest. Groups were compared regarding volumes at clinic presentation and annual change rates. Baseline volumes, especially of grey matter compartments, were significantly reduced in bvFTD and AD patients. Grey matter volumes of the caudate and the gyrus rectus were significantly smaller in bvFTD than AD. The bvFTD group could be separated from AD on the basis of caudate volume with high accuracy (79% cases correct). Annual volume decline was markedly larger in bvFTD and AD than controls, predominantly in white matter of temporal structures. Decline in grey matter volume of the lateral orbitofrontal gyrus separated bvFTD from AD and controls. Automated longitudinal MRI volumetry discriminates bvFTD from AD. In particular, greater reduction of orbitofrontal grey matter and temporal white matter structures after 12 months is indicative of bvFTD

Undertaking multi-centre randomised controlled trials in primary care: learnings and recommendations from the PULsE-AI trial researchers

Background Conducting effective and translational research can be challenging and few trials undertake formal reflection exercises and disseminate learnings from them. Following completion of our multicentre randomised controlled trial, which was impacted by the COVID-19 pandemic, we sought to reflect on our experiences and share our thoughts on challenges, lessons learned, and recommendations for researchers undertaking or considering research in primary care. Methods Researchers involved in the Prediction of Undiagnosed atriaL fibrillation using a machinE learning AlgorIthm (PULsE-AI) trial, conducted in England from June 2019 to February 2021 were invited to participate in a qualitative reflection exercise. Members of the Trial Steering Committee (TSC) were invited to attend a semi-structured focus group session, Principal Investigators and their research teams at practices involved in the trial were invited to participate in a semi-structured interview. Following transcription, reflexive thematic analysis was undertaken based on pre-specified themes of recruitment, challenges, lessons learned, and recommendations that formed the structure of the focus group/interview sessions, whilst also allowing the exploration of new themes that emerged from the data. Results Eight of 14 members of the TSC, and one of six practices involved in the trial participated in the reflection exercise. Recruitment was highlighted as a major challenge encountered by trial researchers, even prior to disruption due to the COVID-19 pandemic. Researchers also commented on themes such as the need to consider incentivisation, and challenges associated with using technology in trials, especially in older age groups. Conclusions Undertaking a formal reflection exercise following the completion of the PULsE-AI trial enabled us to review experiences encountered whilst undertaking a prospective randomised trial in primary care. In sharing our learnings, we hope to support other clinicians undertaking research in primary care to ensure that future trials are of optimal value for furthering knowledge, streamlining pathways, and benefitting patients

Altered splicing of the BIN1 muscle-specific exon in humans and dogs with highly progressive centronuclear myopathy

Amphiphysin 2, encoded by BIN1, is a key factor for membrane sensing and remodelling in different cell types. Homozygous BIN1 mutations in ubiquitously expressed exons are associated with autosomal recessive centronuclear myopathy (CNM), a mildly progressive muscle disorder typically showing abnormal nuclear centralization on biopsies. In addition, misregulation of BIN1 splicing partially accounts for the muscle defects in myotonic dystrophy (DM). However, the muscle-specific function of amphiphysin 2 and its pathogenicity in both muscle disorders are not well understood. In this study we identified and characterized the first mutation affecting the splicing of the muscle-specific BIN1 exon 11 in a consanguineous family with rapidly progressive and ultimately fatal centronuclear myopathy. In parallel, we discovered a mutation in the same BIN1 exon 11 acceptor splice site as the genetic cause of the canine Inherited Myopathy of Great Danes (IMGD). Analysis of RNA from patient muscle demonstrated complete skipping of exon 11 and BIN1 constructs without exon 11 were unable to promote membrane tubulation in differentiated myotubes. Comparative immunofluorescence and ultrastructural analyses of patient and canine biopsies revealed common structural defects, emphasizing the importance of amphiphysin 2 in membrane remodelling and maintenance of the skeletal muscle triad. Our data demonstrate that the alteration of the muscle-specific function of amphiphysin 2 is a common pathomechanism for centronuclear myopathy, myotonic dystrophy, and IMGD. The IMGD dog is the first faithful model for human BIN1-related CNM and represents a mammalian model available for preclinical trials of potential therapies

Care coordination experiences of people with traumatic brain injury and their family members in the 4-years after injury: a qualitative analysis

Title: Care coordination experiences of people with traumatic brain injury and their family members 4-years after injury: A qualitative analysis. Aim: To explore experiences of care coordination in the first 4-years after severe traumatic brain injury (TBI). Methods: A qualitative study nested within a population-based longitudinal cohort study. Eighteen semi-structured telephone interviews were conducted 48-months post-injury with six adults living with severe TBI and the family members of 12 other adults living with severe TBI. Participants were identified through purposive sampling from the Victorian State Trauma Registry. A thematic analysis was undertaken. Results: No person with TBI or their family member reported a case manager or care coordinator were involved in assisting with all aspects of their care. Many people with severe TBI experienced ineffective care coordination resulting in difficulty accessing services, variable quality in the timing, efficiency and appropriateness of services, an absence of regular progress evaluations and collaboratively formulated long-term plans. Some family members attempted to fill gaps in care, often without success. In contrast, effective care coordination was reported by one family member who advocated for services, closely monitored their relative, and effectively facilitated communication between services providers. Conclusion: Given the high cost, complexity and long-term nature of TBI recovery, more effective care coordination is required to consistently meet the needs of people with severe TBI.Sandra Braaf, Shanthi Ameratunga, Nicola Christie, Warwick Teague, Jennie Ponsford, Peter A. Cameron, Belinda J. Gabb

Using Time-Resolved Fluorescence to Measure Serum Venom-Specific IgE and IgG

We adapted DELFIA™ (dissociation-enhanced lanthanide fluoroimmunoassay), a time resolved fluorescence method, to quantitate whole venom specific and allergenic peptide-specific IgE (sIgE), sIgG1 and sIgG4 in serum from people clinically allergic to Australian native ant venoms, of which the predominant cause of allergy is jack jumper ant venom (JJAV). Intra-assay CV was 6.3% and inter-assay CV was 13.7% for JJAV sIgE. DELFIA and Phadia CAP JJAV sIgE results correlated well and had similar sensitivity and specificity for the detection of JJAV sIgE against intradermal skin testing as the gold standard. DELFIA was easily adapted for detecting sIgE to a panel of other native ant venoms