Myer Foundation

Endometrial receptivity occurs during a limited time in the menstrual cycle called the 'window of implantation' (WOI) and is required for successful implantation. Endometrial luminal epithelial cells become adhesive to facilitate embryo attachment and implantation; however, how this occurs is poorly understood. We recently identified that myosin heavy chain 10 (MYH10) was abnormally downregulated in infertile organoid endometrial epithelial cells during the WOI, suggesting a role in receptivity. MYH10 regulates cell polarity, adhesion and migration; however, whether it regulates receptivity is unknown. Our research investigated whether MYH10 regulates endometrial epithelial cell adhesive capacity. MYH10 is localized to all major cellular compartments within the endometrium. Immunostaining intensity was higher in luminal epithelial cells during the WOI compared to the proliferative phase in fertile endometrium. However, MYH10 staining was decreased in infertile endometrium. siRNA knockdown of MYH10 in the Ishikawa cell line significantly decreased cell adhesion to human cytotrophoblast-progenitor spheroids. MYH10 knockdown increased PGR and FOXO1 while decreasing PDLIM2 expression. Proteomics analysis following MYH10 knockdown demonstrated altered production of 57 proteins with functions critical in receptivity, including tight junctions. These results demonstrate that MYH10 alters endometrial epithelial cell adhesive capacity primarily via regulation of the actin cytoskeleton, implying an important role in implantation.

Does the addition of three antioxidants to culture media during gamete collection, insemination, and embryo culture increase the clinical pregnancy rate from fresh blastocyst transfers? The clinical pregnancy rate from fresh blastocyst transfers was not increased by the addition of antioxidants to IVF and embryo culture media. Addition of antioxidants to media is beneficial in mouse IVF, embryo culture, and cryopreservation. Prospective clinical trials of sibling human oocytes found an improvement in embryo quality and increased pregnancy rates from frozen blastocyst transfers in older patients. Single-centre, prospective randomized controlled trial, superiority study comparing media with or without the addition of antioxidants from January 2019 to November 2021. A total of 1482 patients were randomized before egg collection. Patients and their doctors were blinded to the treatment group. Patients undergoing IVF/ICSI cycles and intending to undergo a fresh transfer of a single blastocyst were recruited. Exclusion criteria were previous participation in the study, use of cryopreserved oocytes/embryos, artificial oocyte activation, freeze-all cycle, or extraction of sperm from testicular biopsy. Seven hundred thirty-nine patients were randomized to control media and 743 patients to media containing the 'A3' antioxidant combination of acetyl-L-carnitine, α-lipoic acid, and N-acetyl-L-cysteine (treatment group). The clinical pregnancy rate per randomized patient per cycle from fresh embryo transfer was not different between the control and antioxidant media (26.1% vs 22.9%; P > 0.05; RR 0.88 (95% CI 0.73-1.05)). In the Per Protocol population, which excludes patients with protocol violations or without a fresh transfer due to freeze-all or no embryo available, there was also no difference in between the control and antioxidant media in clinical pregnancy rate (36.7% vs 33.2%; P > 0.05; RR 0.90 (95% CI 0.76-1.07)) and live birth rate (32.4% vs 29.5%, P > 0.05). In the Intention-to-Treat population, antioxidant media produced a significant increase in the fertilization rate from 59.2 ± 26.3% to 64.5 ± 25.4% (P < 0.001) compared to control media. Blastocyst development rate per fertilized oocyte was not affected by antioxidant media, but the higher fertilization rate resulted in more fertilized oocytes per patient and therefore more blastocysts utilized per patient in the antioxidant group compared to the control (2.70 ± 2.59 vs 3.09 ± 2.96, P < 0.01). The increase in fertilization rate was observed in a subgroup analysis of ICSI cycles (57.9 ± 27.2% vs 68.3 ± 24.7%, P < 0.0001), and a decrease in the number of cycles with failed fertilization from 8.0 to 3.7% with antioxidant media (P < 0.01). In contrast, there was no effect of antioxidant media on fertilization rate in cycles with IVF insemination. This was a single-centre study, so the effects of antioxidant media in clinics with different protocols are unknown. Patient oxidative stress, which may be influenced by inflammation, diet, smoking status, antioxidant supplement consumption, and other lifestyle factors, was not accounted for. Any potential effect of renewing the antioxidants in the media during culture was not examined. Addition of antioxidants to culture media did not affect pregnancy rates from fresh single embryo transfers. An increase in fertilization rate was observed, which resulted in more blastocysts available for transfer and cryopreservation. There was no effect of antioxidants on blastocyst development rate or grade. Further studies are needed to validate the observed effect of antioxidants on fertilization rate following ICSI. Culture media and an independent statistician were funded by Vitrolife AB. R.L.K has received travel funding and a speaker's honorarium from Vitrolife. D.K.G. has received research grants from Vitrolife at the University of Melbourne. N.-G.P. has received consulting fees from Vitrolife for work related to the study. All other authors have nothing to declare. ACTRN12618001479291. 4 September 2018. 28 January 2019.

ABSTRACTBackgroundTailored disability support is fundamental to the lives of adults with disability and complex needs. However, support quality is inconsistent. An intervention was co‐designed to help people with disability direct their supports: participant‐led videos (PLVs). Following a successful pilot study, this study aimed to evaluate the feasibility of the use of PLVs by sector professionals working with people with disability in the community.MethodsSixteen sector professionals attended a training workshop on PLVs. Following the workshop, five sector professionals were funded to collaborate with people with disability to produce PLVs. The training workshop was evaluated using an online survey (n = 15) and a 1‐month follow‐up interview (n = 8). Post‐production interviews (n = 4) were conducted to evaluate the experience of producing a PLV.ResultsAll sector professionals endorsed the training workshop and reported high levels of confidence in producing videos following the workshop. Highlights of the workshop included the centrality of the voice of people with disability and the design and quality of the content. All participants planned to implement what they had learnt and create videos with people they worked with. The experience evaluation findings were also positive, with all sector professionals endorsing the usefulness of PLVs as a tool to capture genuine behaviours and enable disability support workers to get to know the individual. Sector professionals saw the value of the intervention in helping to give people with disability a voice and minimise misrepresentation of individuals.ConclusionsThis study demonstrates the feasibility of PLVs outside of the team that developed the intervention. This evaluation contributes to an evidence base for funding to facilitate the development of PLVs as a tool to help improve the quality of support and maximise autonomy for people with complex needs. Future research is required to evaluate the longer‐term impact of PLVs on support quality.

Background Co-design is gaining momentum in disability. However, there is limited research evidence to guide co-designing with people with acquired neurological disability. The aim of this scoping literature review was to understand when and how co-design is used with adults with acquired neurological disability, as well as the experience of participating in co-design. Methods Systematic searches were conducted in CINAHL, MEDLINE, PsycINFO, Scopus and Embase databases. The search was limited to qualitative studies or studies using mixed methods in which qualitative data could be extracted for thematic analysis. Results Of the 4200 articles retrieved, 45 were eligible for the review. Data extracted across the included studies showed variability in the definition and implementation of co-design, including recruitment, timing and the role of co-design contributors. Thematic analysis of the lived experience resulted in three themes: (1) a meaningful experience, (2) balancing group dynamics, and (3) an unfamiliar process. Conclusions Co-design with adults with acquired neurological disability is an emerging area of practice, valued by co-design contributors with disability, health professionals and researchers. Future work is needed to better define and operationalise co-design, with investment in the facilitator role to optimise involvement of people with disability.

Background:Socio-economic disparities in stillbirth persist in Australia and other high-income countries. Despite increased attention to disparities in perinatal outcomes, including stillbirth, very little is known about the way conversations about stillbirth prevention are occurring within pregnancy care.Objectives:Understand how conversations about stillbirth prevention are experienced by parents of refugee and migrant backgrounds, interpreters, and healthcare professionals within public maternity services in Victoria and South Australia.Design:An interpretive qualitative design was used.Methods:Semi-structured interviews with 62 participants: 47 parents of refugee and migrant backgrounds, six midwives, five medical doctors, and four interpreters. Data were analysed using reflexive thematic analysis.Results:Analysis produced three themes: (1) searching for the right balance, reflecting health professionals’ hesitation to provide direct information if it might promote unnecessary distress or fear, or result in parents’ feeling coerced into medical intervention; (2) patterns and consequences of culturally unsafe care, situating conversations about stillbirth prevention within complex interpersonal and systemic contexts; and (3) safety within relationships built with time, illustrating time and trusting relationships as integral to culturally safe care. Health professionals’ hesitation to discuss stillbirth prevention directly with families restricts access to important health information for a population already facing numerous, longstanding barriers to high-quality maternity care. Distrust between parents, health professionals, and interpreters, fuelled by fragmented and time-poor maternity service design and delivery, can undermine the possibility of culturally safe conversations about stillbirth prevention.Conclusion:Investment to make culturally safe pregnancy care possible for women and families of refugee and migrant backgrounds is integral to reducing preventable stillbirths.

The impact of Multiple Sclerosis (MS) on mobility and other functions varies considerably and the trajectory of the disease is unpredictable. People often need timely funding for home modifications, with some needing specialist disability housing and support. This rapid review examined existing literature on the housing needs of people with MS. A representative reference group guided our process. Concentrating on the home environment, we systematically searched peer-reviewed literature through three databases and grey literature using a focused web-based process. The inclusion of 19 peer-reviewed articles and 13 grey literature documents revealed the need for accessible housing, affordable in-home assistive technology, and proximity to the community. A lack of timely funding was a primary barrier to independence in the home, resulting in calls for financial aid that is responsive to the progressive nature of MS. People with MS need comprehensive support, including timely access to information, affordable and accessible housing, and funding for necessary home modifications. These resources are crucial to promote independence at home, reduce hospitalisations, and prevent early admission to residential aged care. Further research is needed to capture the unique barriers people with MS face in their local context as a precursor to developing participant-led recommendations.

The proposed study reports the design and development of a rapid screening tool, the Systems Neuroscience Test Battery (SNTB), for diagnosing and evaluating the neurological manifestations of Post-COVID-19 Neurological Syndrome (PCNS) within the broader context of Post-Acute Sequelae to COVID-19 (PASC). The SNTB is designed to incorporate a behaviorally relevant Telehealth component that enhances consumer confidence in symptom discrimination, management of PCNS, and guides rehabilitation programs while allowing for continuous evaluation of intervention effectiveness. The study employs a longitudinal design, with telehealth and routine blood assessments conducted at three-month intervals, including at least two follow-ups post-recruitment. These assessments will involve Consumer-Reported Symptoms, Clinical History, Neuropsychological Data, and Timed Psychophysics, aimed at rapid screening of PCNS-related symptoms including ‘brain fog” and its affect on visually driven attention, cognition and visually driven motor behaviors. These assessments are intended to validate the characteristics of ‘brain fog’ and identify predictive behavioral biomarkers for the development of PCNS. The target population includes adults aged 18–65 who have experienced persistent neurological symptoms for at least three months following a confirmed COVID-19 infection. Exclusion criteria include individuals unable to undergo radiological examinations, such as pregnant women or those with contraindications to MRI, ensuring the robustness of the sample and reducing potential selection bias. The SNTB tool will facilitate the online identification of predictive biomarkers for PCNS and aid in the discovery of effective molecular biomarker combinations for medical intervention and rehabilitation. Complementary to the Telehealth Assessment, hospital facilities will be utilized for radiological and blood-based molecular assessments, ensuring concurrent profiling of structural and functional changes during ‘brain fog’ and recovery from PCNS symptoms.

Respiratory syncytial virus (RSV) is a major cause of respiratory infection with a higher burden in Aboriginal and Torres Strait Islander infants and children. We conducted a pilot qualitative study identifying disease knowledge and willingness to immunise following the changing immunisation landscape for infant RSV in 2024. Yarning groups were held with a convenience sample of parents/carers of Aboriginal children attending playgroup at a metropolitan Aboriginal Health Service in Western Australia. Data collected in the form of notes were thematically analysed. We heard from nine parents/carers over two yarns in March/April 2024. Level of RSV awareness largely depended on lived experience of an RSV infection with some participants only first hearing of RSV following announcement of the immunisation program. Most participants were willing to accept immunisation. There was a strong preference for information on disease and immunisation safety coming from a 'trusted Aboriginal voice', but the level of information varied. This pilot study provides initial insights into community views of RSV disease and immunisation. More RSV disease awareness is needed in the Indigenous community. These findings will help inform current and future RSV immunisation programs for Aboriginal and Torres Strait Islander populations.

To compare the use of orifice barriers (OB) in root-filled teeth (RFT) between specialist endodontic practitioners (SEP) and general and other specialist practitioners (GDP+), and identify common materials, reasons for selection, and techniques. An online survey was distributed to SEP and GDP+ practising in Australia. Demographic and multiple-choice questions relating to material selection and technique choices were asked to evaluate and relate usage patterns to practising and training backgrounds. Fisher's exact tests were undertaken to compare categorical variables across practitioner groups. Significance level was set at p<.05. There were 457 eligible responses: 393(86%) GDP+ and 64(14%) SEP. Of 429 reporting endodontically treating or restoring teeth, 317(73.9%) placed OB; preferred depth of root filling removal by most (91.8%) was ≤ 2 mm, with more SEP preferring 2 mm than GDP+(p=.02). Preferred materials for OB were conventional and resin-modified GIC (GIC), resin composite materials (RC), Cavit™ and zinc polycarboxylate cement (ZPC). 'Ease of use' was a common reason among all practitioners for GIC and RC. Significantly more SEP(p<.001) chose ZPC in all teeth and more commonly because of 'Ease of use' for both posterior (p<.001) and anterior (p=.002) teeth. All ZPC-using SEP preferred using a paste-filler/lentulo spiral, significantly more than GDP+ for posterior (p<.001) and anterior (p=.002) teeth. Cavit™ was often chosen for 'Sealing ability'. OB were widely placed by dental practitioners in Australia, with a small group of materials selected, most commonly for ease of use or sealing ability. The findings of this study suggest that further research should be undertaken to investigate the relative performance of these materials as OB and to inform the clinician's choices when restoring RFT.