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Protein Disulfide Isomerase Endoplasmic Reticulum Protein 57 (ERp57) is Protective Against ALS-Associated Mutant TDP-43 in Neuronal Cells
Amyotrophic Lateral Sclerosis (ALS) is a severe neurodegenerative disease affecting motor neurons. Pathological forms of Tar-DNA binding protein-43 (TDP-43), involving its mislocalisation to the cytoplasm and the formation of misfolded inclusions, are present in almost all ALS cases (97%), and ~ 50% cases of the related condition, frontotemporal dementia (FTD), highlighting its importance in neurodegeneration. Previous studies have shown that endoplasmic reticulum protein 57 (ERp57), a member of the protein disulphide isomerase (PDI) family of redox chaperones, is protective against ALS-linked mutant superoxide dismutase (SOD1) in neuronal cells and transgenic SOD1G93A mouse models. However, it remains unclear whether ERp57 is protective against pathological TDP-43 in ALS. Here, we demonstrate that ERp57 is protective against key features of TDP-43 pathology in neuronal cells. ERp57 inhibited the mislocalisation of TDP-43M337V from the nucleus to the cytoplasm. In addition, ERp57 inhibited the number of inclusions formed by ALS-associated variant TDP-43M337V and reduced the size of these inclusions. ERp57 was also protective against ER stress and induction of apoptosis. Furthermore, ERp57 modulated the steady-state expression levels of TDP-43. This study therefore demonstrates a novel mechanism of action of ERp57 in ALS. It also implies that ERp57 may have potential as a novel therapeutic target to prevent the TDP-43 pathology associated with neurodegeneration
Internationalization Through Digital Empowerment for Women Filigree Jewelry Artisan Entrepreneurs in Portugal
The purpose of this study is to examine how Portuguese women jewelry artisan entrepreneurs are empowered using digital technology. Recently, there has been an emphasis on the artisan and craft industry due to renewed interest in handicrafts but limited research exists about how digital and international entrepreneurship has influenced its growth. This study focuses on this gap by stressing the need to take a gender lens on international digital business activity in terms of how it is conducted. In-depth semistructured interviews with women jewelry makers located in Portugal were conducted to understand how their digital experiences led to increased levels of internationalization. The findings suggest that the use of digital technology was supported by co-creation, internationalization, and sustainability initiatives. The results of the study highlight the way crisis conditions from the COVID-19 pandemic led to increased emphasis by artisan entrepreneurs on digital entrepreneurship and this had flow-on effects leading to higher internationalization rates
Effect of fractional exhaled nitric oxide (F<sub>ENO</sub>)-based asthma management during pregnancy versus usual care on infant development, temperament, sensory function and autism signs
Asthma during pregnancy is associated with a range of adverse perinatal outcomes. It is also linked to increased rates of neurodevelopmental conditions in the offspring. We aimed to assess whether fractional exhaled nitric oxide (FENO)-based asthma management during pregnancy improves child developmental and behavioural outcomes compared to usual care. The Breathing for Life Trial was a randomised controlled trial that compared FENO-based asthma management during pregnancy to usual care. Participants were invited to the developmental follow-up, the Breathing for Life Trial – Infant Development study, which followed up infants at 6 weeks, 6 months and 12 months. The primary outcomes were measured in infants at 12 months using the Bayley-III: Cognitive, Language and Motor composite scores. Secondary outcomes included Bayley-III social-emotional and adaptive behaviour scores, autism likelihood and sensory and temperament outcomes. The exposure of interest was the randomised intervention group. Two hundred and twenty-two infants and their 217 participating mothers were recruited to the follow-up; 107 mothers were in the intervention group and 113 were in the control group. There was no evidence of an intervention effect for the primary outcomes: Bayley-III cognitive (mean = 108.9 control, 108.5 intervention, p = 0.93), language (mean = 95.9 control, 95.6 intervention, p = 0.87) and motor composite scores (mean = 97.2 control, 97.9 intervention, p = 0.25). Mean scores for secondary outcomes were also similar among infants born to control and FENO group mothers, with few results reaching p < 0.05. Conclusion: In this sample, FENO-guided asthma treatment during pregnancy did not improve infant developmental outcomes in the first year of life. </p
The Autonomist Imaginary
A thesis submitted in total fulfilment of the requirements for the degree of Doctor of Philosophy to the School of Social Sciences, Faculty of Sociology and Anthropology, La Trobe University, Victoria, Australia.</p
Understanding the long-term geochemical pathways of mining waste using legacy tailings from Victorian goldfields
A thesis submitted in total fulfilment of the requirements for the degree of Doctor of Philosophy to the School of Agriculture, Biomedicine and Environment, La Trobe University, Victoria, Australia.</p
The Case for Knowledge Insertion
Submitted in total fulfillment of the requirements for the degree of Master of Arts to the School of Humanities and Social Sciences, La Trobe University, Victoria, Australia.</p
Methods of Determining Energy Expenditure in Individuals with Prader-Willi Syndrome: A Systematic Literature Review
Prader-Willi syndrome (PWS) is a rare disorder characterised by varying nutritional phases that occur throughout the lifespan, ranging from failure to thrive to hyperphagia. If uncontrolled, the imbalance between energy intake and expenditure results in obesity development and increased morbidity and mortality risk. Although measures of energy requirements for accurate nutrition assessment are vital, the evidence appears sparse and heterogeneous; hence, the aim of this review was to examine the available literature on energy expenditure predicted or measured using various methods in individuals with PWS. Studies were sought that presented methods and results on resting energy expenditure or basal metabolic rate. A narrative synthesis was completed to present the study characteristics and results. Methods of determining energy requirements included predictive equations and indirect calorimetry. Differences amongst ages, growth hormone therapy, fasting status, and measures in which results were presented were limitations to appropriately summarising and identifying trends in energy expenditure. Indirect calorimetry was identified as the most accurate method; however, it is not widely available in all settings. Further research is encouraged to support the development of valid and reliable predictive equations that will better inform and improve the efficiency of clinical practice in supporting people with PWS
‘You Just Struggle on Your Own’: Exploring Older People and Their Caregivers' Perspectives About Falls Prevention Education in Hospitals
Background: Providing older patients with an opportunity to participate in individualised falls preventive education, has been shown to reduce hospital falls. However, few studies have explored older peoples' perspectives of hospital falls prevention education. This study aimed to explore older people and their caregivers' knowledge and awareness about hospital falls prevention, including their reflections on the education they received when hospitalised. Methods: A qualitative, exploratory study with focus groups and semistructured interviews was conducted. Participants were a purposively selected sample of community-dwelling older people (65+ years) admitted to a hospital in the past 5 years and caregivers of older people. Data were thematically analysed using deductive and inductive approaches, and a capability–opportunity–motivation–behaviour model was applied to understand key determinants of implementing falls education for hospitalised older people. Results: Participants' [n = 46 (older people n = 37, age range 60–89 years), caregivers n = 9] feedback identified five themes: distress and disempowerment if the participant did have a hospital fall or nearly fell, anxiety and uncertainty about what behaviour was required while in hospital, insufficient and inconsistent falls prevention education, inadequate communication and underlying attitudes of ageism. Applying a behaviour change model suggested that older people and their caregivers did not develop falls prevention knowledge, awareness or motivation to engage in falls prevention behaviour. Older people were also provided with limited opportunities to engage in falls preventive behaviour while in hospital. Conclusion: Older people in our study received sporadic education about falls prevention during their hospital admissions which did not raise their awareness and knowledge about the risk of falls or their capability to engage in safe falls preventive behaviour. Conflicting messages may result in older people feeling confused and anxious about staying safe in hospital
What is 'physiological birth'? A scoping review of the perspectives of women and care providers.
Problem: Physiological birth was defined by the World Health Organization in 1997, however, clinical practices in childbirth have changed considerably since this time. Background: Ambiguous terms in healthcare such as ‘physiological birth’ may cause confusion amongst care providers and consumers. Aim: To identify what is known about physiological birth, and how perceptions of physiological birth manifest in current literature. Methods: This review followed the Joanna Briggs Institute methodology for scoping reviews and the PRISMA-ScR checklist. Four databases were searched using keywords relating to physiological birth. Relevant studies were identified using agreed criteria, and data were extracted and synthesised. Results: A total of 24 studies met the inclusion criteria for this review. Three connected factors were identified: (1) Physiological birth in a risk-averse system, (2) Dominant voices in birth, and (3) Lack of exposure to physiological birth. No unified universal definition of physiological birth was identified in the literature. Discussion: ‘Physiological birth’ as a term lacks consistency. A risk-averse healthcare system could be a barrier to physiological birth. Dominant voices in the birthing space can dictate the way birth occurs. Lack of exposure to physiological birth may diminish the acquisition and maintenance of important skills and knowledge among care providers. Recognising the factors important to women could lead to a positive birth experience. Conclusion: Excluding a woman's subjective experience from health professionals’ understanding of physiological birth increases the likelihood of risk management being the paramount objective in clinical decision-making. We propose it is timely to align clinical understanding of physiological birth with midwifery's woman-centred professional philosophy