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Abstract Preclinical methods are needed for screening potential Alzheimer’s disease (AD) therapeutics that recapitulate phenotypes found in the Mild Cognitive Impairment (MCI) stage or even before this stage of the disease. This would require a phenotypic system that reproduces cognitive deficits without significant neuronal cell death to mimic the clinical manifestations of AD during these stages. Long-term potentiation (LTP), which is a correlate of learning and memory, was induced in mature human iPSC-derived cortical neurons cultured on microelectrode arrays utilizing circuit patterns connecting two adjacent electrodes. We demonstrated an LTP system that modeled the MCI and pre-MCI stages of Alzheimer’s and validated this functional system utilizing four AD therapeutics, which was also verified utilizing patch-clamp electrophysiology. LTP was induced by tetanic electrical stimulation, and LTP maintenance was significantly reduced in the presence of Amyloid-Beta 42 (Aβ42) oligomers compared to the controls, however, co-treatment with AD therapeutics (Donepezil, Memantine, Rolipram and Saracatinib) corrected Aβ42-induced LTP impairment. The results illustrate the utility of the system as a validated platform to model MCI AD pathology, and potentially for the pre-MCI phase before significant neuronal death. This system also has the potential to become an ideal platform for high-content therapeutic screening for other neurodegenerative diseases.

Abstract Background Diet and exercise are important components of treatment for complex chronic conditions, however access to allied health support is limited. When available, support is often siloed and fragmented. Digital health incorporating patient choice may help to align health care services with preferences and goals. This study evaluated the implementation of a ubiquitously accessible patient-centred digital health diet and exercise service. Methods U-DECIDE was a single-centre, 26-week randomised controlled trial set in kidney and liver disease clinics in a tertiary hospital in Brisbane, Australia. Participants were adults with a complex chronic condition referred for dietetic consultation with at least one feature of the metabolic syndrome. All participants received a dietary consultation, an activity monitor and usual care. Intervention participants were offered one text message per week and access to additional digital health options (increased text message frequency, nutrition app, exercise app, group-based diet and/or exercise video consultations). The primary outcome of feasibility was determined by safety (study-related serious adverse events: SRSAEs), recruitment (≥ 50% eligible patients), retention (≥ 70%), exposure uptake (≥ 75% of intervention group had greater access to health professional contact than comparator) and video consultation adherence (≥ 80% attendance). Secondary outcomes included process evaluation metrics and clinical outcomes. Results Of 67 participants (intervention n = 33, comparator n = 34), 37 (55%) were men, median (IQR) age was 51 (41–58) years. The most chosen digital health options were the nutrition app (n = 29, 88%) and exercise video consultations (n = 26, 79%). Only one participant chose no additional digital health options. The intervention group had no SRSAEs. The study exceeded targets for recruitment (52%), retention (81%) and exposure uptake (94%). Video consultation adherence was 42%. Engagement across digital health options was inconsistent. Conclusions Digital health options incorporating patient choice were feasible and can be offered to people with complex chronic disease as a service model option. Trial registration Australia and New Zealand Trials Register: Trial Registration Number: ACTRN12620001282976. Registered 27th November 2020.

The pioneer microbiome is the initial colonization and establishment of microorganisms within the neonate. The objective of this project was to quantify maternal and environmental contributions to the piglet's pioneer microbiome. Sterile swabs were used to collect samples from the gilt’s rectum, the farrowing crate before and after gilts were moved in, the gilt’s birth canal during farrowing, and the piglet’s rectum on days 0 (prior to suckling), 3, and 10 post farrowing and at weaning (21.6 ± 1.0 days post farrowing). During farrowing, colostrum was collected from each gilt from a representative sample of teats into a single sterile collection cup. Bacterial DNA extraction and sequencing targeted the V4 hypervariable region of the 16S rRNA gene. The relative abundance of Lactobacillus in the piglet microbiome was lower on day 3 compared to day 0, day 10, and at weaning (P < 0.05). For alpha diversity, piglet samples exhibited distinct clustering for bacterial richness by day (P < 0.01). Multiple regression analyses indicated that the birth canal explained 51.6% of the variation observed in the piglet day 0 microbiome (P < 0.0001) and 6.5% of the variation in the piglet day 10 microbiome (P = 0.013). The day 10 microbiome explained 58.6% of the variation observed in the piglet microbiome at weaning (P < 0.0001). Bacterial communities of the farrowing crate and colostrum did not impact the piglet microbiome for any day (P > 0.10). The results indicate that the piglet pioneer microbiome is largely influenced by the microbiome of the birth canal.

Objective The acceptability of being offered a choice from a suite of digital health service options to support optimal diet and exercise behaviors in adults with complex chronic conditions was evaluated. This study sought to understand many areas of acceptability including satisfaction, ease of use, usefulness and user appropriateness and perceived effectiveness. Methods This mixed-methods study was embedded within a randomized-controlled feasibility trial providing digital health services managing diet and exercise for adults from specialist kidney and liver disease clinics. Post study surveys and semistructured interviews were used to determine patients’ acceptability of the trial interventions. Quantitative (surveys) and qualitative (surveys and interviews) results were merged using integrative analysis and mapped to each construct of the modified version of the Theoretical Framework of Acceptability. Results Seventeen interviews (intervention group) and 50 surveys ( n = 24 intervention, n = 26 comparator) completed from a possible 67 participants were analyzed. In the intervention group, the survey results revealed high areas of acceptability for the digital health services including overall support received, ease of use, timely advice and feeling safe. The interviews also revealed high areas of acceptability including convenience, ability to adopt healthier behaviors and having regular interactions with health professionals. However, the interviews also revealed lower areas of acceptability as a result of absence of individualization, low digital literacy, and limitations from life circumstances. Conclusions Recipients of digital health services that supported diet and exercise interventions found these useful, effective, and safe. Individualized care, technical support and patient confidence remain important to improve the acceptability of digital health service interventions.

Prior studies in beef cattle have shown shifts in the reproductive microbiome prior to artificial insemination (AI), yet few have characterized both the reproductive microbiome and immune responses prior to AI, particularly in purebred Bos indicus. Therefore, the aim of this study was to characterize the circulating cytokines and the vaginal microbiome of Bos indicus females prior to fixed-time artificial insemination (FTAI). Bos indicus females (n = 79) on four separate ranch operations within a 20-mile radius in East Texas were subjected to the 7-day CO-Synch + controlled intervaginal drug-releasing (CIDR) protocol beginning on day (d)-9 with FTAI on d0. Blood samples were collected on d-9 (CIDR IN), d-2 (CIDR OUT), and d0 (AI DAY) for cytokine concentration analyses using the RayBiotech Quantibody Bovine Cytokine Array Q1 kit per the manufacturer’s instructions. Sterile vaginal swabs were inserted past the vulva, rotated, and stored at -80°C for microbiome analysis. Bacterial community analyses targeted the V4 hypervariable region of the 16S rRNA gene. Pregnancy status was determined by transrectal ultrasonography approximately 60 days after FTAI for resulting open females (n = 45) and pregnant females (n = 34). Regardless of pregnancy status, the vaginal relative abundance of Firmicutes differed between CIDR IN, CIDR OUT, and AI DAY (63.74% vs. 28.31% vs. 60.86% ± 3.66%, respectively; P < 0.01). Genera with phylum Firmicutes including Ruminococcus, Clostridium, Blautia, Butyrvibrio, and Mogibacterium followed a similar trend (P < 0.05). Butyrvibrio tended to have greater relative abundance in the vaginal samples of Cows than Heifers (4.17% ± 0.75% vs. 3.26% ± 0.77%; P = 0.07). Concentrations of the interferon (IFN)γ (2005.98 ± 471.94 pg/mL vs. 1185.40 ± 482.65 pg/mL; P < 0.01), interleukin (IL)1F5 (153.89 ± 141.07 pg/mL vs. 627.30 ± 149.28 pg/mL; P < 0.01), and interferon gamma-induced protein (IP)10 (9363.26 ± 2929.83 pg/mL vs. 5905.53 ± 2983.60 pg/mL; P = 0.05) were greater in Cows than Heifers. There was a parity-by-status interaction for IP10, with Open Cows having the greatest concentration compared all other groups (P < 0.05). These results indicate differences in circulating cytokines and shifts in the vaginal microbiome for in Bos indicus cattle prior to FTAI.

Abstract Background In Australia, the overall prevalence of liver disease is increasing. Maximising uptake of community screening programmes by understanding patient preferences is integral to developing consumer-centred care models for liver disease. Discrete choice experiments (DCEs) are widely used to elicit preferences for various healthcare services. Attribute development is a vital component of a well-designed DCE and should be described in sufficient detail for others to assess the validity of outcomes. Hence, this study aimed to create a list of potential attributes and levels which can be used in a DCE study to elicit preferences for chronic liver disease screening programmes. Methods Key attributes were developed through a multi-stage, mixed methods design. Focus groups were held with consumers and health care providers on attributes of community screening programmes for liver disease. Stakeholders then prioritised attributes generated from the focus group in order of importance via an online prioritisation survey. The outcomes of the prioritisation exercise were then reviewed and refined by an expert panel to ensure clinically meaningful levels and relevance for a DCE survey. Results Fifteen attributes were generated during the focus group sessions deemed necessary to design liver disease screening services. Outcomes of the prioritisation exercise and expert panel stages recognised five attributes, with three levels each, for inclusion in a DCE survey to elicit consumer preferences for community screening for liver disease. This study also highlights broader social issues such as the stigma around liver disease that require careful consideration by policy makers when designing or implementing a liver screening programme. Conclusions The attributes and levels identified will inform future DCE surveys to understand consumer preferences for community screening programmes for liver disease. In addition, the outcomes will help inform the implementation of the LOCATE-NAFLD programme in real-world practice, and could be relevant for other liver and non-liver related chronic disease screening programmes.

Abstract A functional, multi-organ, serum-free system was developed for the culture of P. falciparum in an attempt to establish innovative platforms for therapeutic drug development. It contains 4 human organ constructs including hepatocytes, splenocytes, endothelial cells, as well as recirculating red blood cells which allow for infection with the parasite. Two strains of P. falciparum were used: the 3D7 strain, which is sensitive to chloroquine; and the W2 strain, which is resistant to chloroquine. The maintenance of functional cells was successfully demonstrated both in healthy and diseased conditions for 7 days in the recirculating microfluidic model. To demonstrate an effective platform for therapeutic development, systems infected with the 3D7 strain were treated with chloroquine which significantly decreased parasitemia, with recrudescence observed after 5 days. Conversely, when the W2 systems were dosed with chloroquine, parasitemia levels were moderately decreased when compared to the 3D7 model. The system also allows for the concurrent evaluation of off-target toxicity for the anti-malarial treatment in a dose dependent manner which indicates this model could be utilized for therapeutic index determination. The work described here establishes a new approach to the evaluation of anti-malarial therapeutics in a realistic human model with recirculating blood cells for 7 days.

Mongolia experienced a nationwide measles outbreak during 1 March 2015–31 December 2016, with 49,077 cases reported to the WHO; many were among vaccinated young adults, suggesting a possible role of vaccine failure. Advanced laboratory methods, coupled with detailed epidemiological investigations, can help classify cases as vaccine failure, failure to vaccinate, or both. In this report, we conducted a study of cases to identify risk factors for breakthrough infection for a subset of laboratory-confirmed measles cases. Of the 193 cases analyzed, only 19 (9.8%) reported measles vaccination history, and 170 (88%) were uncertain. Measles-specific IgG avidity testing classified 120 (62%) cases as low IgG avidity, indicating no prior exposure to measles. Ten of these cases with low IgG avidity had a history of measles vaccination, indicating primary vaccine failure. Overall, sixty cases (31%) had high IgG avidity, indicating breakthrough infection after prior exposure to measles antigen through vaccination or natural infection, but the IgG avidity results were highly age-dependent. This study found that among young children aged 9 months–5 years, breakthrough infection was rare (4/82, 5%); however, among young adults aged 15–25 years, breakthrough infection due to secondary vaccine failure (SVF) occurred on a large scale during this outbreak, accounting for the majority of cases (42/69 cases, 61%). The study found that large-scale secondary vaccine failure occurred in Mongolia, which highlights the potential for sustained outbreaks in post-elimination settings due to “hidden” cohorts of young adults who may have experienced waning immunity. This phenomenon may have implications for the sustainability of measles elimination in countries that remain vulnerable to the importation of the virus from areas where it is still endemic. Until global measles elimination is achieved, enhanced surveillance and preparedness for future outbreaks in post- or peri-elimination countries may be required.

Polymer-based long-acting injectable drugs are a promising therapeutic strategy for chronic diseases. Here the authors use machine learning to inform the data-driven development of advanced drug formulations.

Khanolkar et al. compare the immune response in perinatally-infected HIV+ patients with differing patterns of virological control on treatment with antiretroviral therapy. Patients with sub-optimally suppressed HIV displayed no deficits in lymphocyte functional fitness.

Paraneoplastic neurological syndromes (PNS) occur in about 1 in 300 cases of cancer. The usual mechanism is that an antigen on the cancer sets off an immune response that then cross-reacts with a nervous system antigen. The presentation is usually with a subacute progressive neurological disorder. The management of these conditions is usually of both the underlying tumor and immunomodulation to suppress the autoimmune response. There are a number of these conditions that can present to the Neuro-Ophthalmology clinic, either as a discrete condition affecting vision or eye movements or as part of a more widespread neurological disorder. This article will discuss these conditions, their management and prognosis.

The control of severe or chronic pain has relied heavily on opioids and opioid abuse and addiction have recently become a major global health crisis. Therefore, it is imperative to develop new pain therapeutics which have comparable efficacy for pain suppression but lack of the harmful effects of opioids. Due to the nature of pain, any in vivo experiment is undesired even in animals. Recent developments in stem cell technology has enabled the differentiation of nociceptors from human induced pluripotent stem cells. This study sought to establish an in vitro functional induced pluripotent stem cells-derived nociceptor culture system integrated with microelectrode arrays for nociceptive drug testing. Nociceptors were differentiated from induced pluripotent stem cells utilizing a modified protocol and a medium was designed to ensure prolonged and stable nociceptor culture. These neurons expressed nociceptor markers as characterized by immunocytochemistry and responded to the exogenous toxin capsaicin and the endogenous neural modulator ATP, as demonstrated with patch clamp electrophysiology. These cells were also integrated with microelectrode arrays for analgesic drug testing to demonstrate their utilization in the preclinical drug screening process. The neural activity was induced by ATP to mimic clinically relevant pathological pain and then the analgesics Lidocaine and the opioid DAMGO were tested individually and both induced immediate silencing of the nociceptive activity. This human-based functional nociceptive system provides a valuable platform for investigating pathological pain and for evaluating effective analgesics in the search of opioid substitutes.

BackgroundThe metabolic syndrome is common across many complex chronic disease groups. Advances in health technology have provided opportunities to support lifestyle interventions. ObjectiveThe purpose of this study is to test the feasibility of a health technology-assisted lifestyle intervention in a patient-led model of care. MethodsThe study is a single-center, 26-week, randomized controlled trial. The setting is specialist kidney and liver disease clinics at a large Australian tertiary hospital. The participants will be adults with a complex chronic condition who are referred for dietetic assessment and display at least one feature of the metabolic syndrome. All participants will receive an individualized assessment and advice on diet quality from a dietitian, a wearable activity monitor, and standard care. Participants randomized to the intervention group will receive access to a suite of health technologies from which to choose, including common base components (text messages) and optional components (online and mobile app–based nutrition information, an online home exercise program, and group-based videoconferencing). Exposure to the optional aspects of the intervention will be patient-led, with participants choosing their preferred level of engagement. The primary outcome will be the feasibility of delivering the program, determined by safety, recruitment rate, retention, exposure uptake, and telehealth adherence. Secondary outcomes will be clinical effectiveness, patient-led goal attainment, treatment fidelity, exposure demand, and participant perceptions. Primary outcome data will be assessed descriptively and secondary outcomes will be assessed using an analysis of covariance. This study will provide evidence on the feasibility of the intervention in a tertiary setting for patients with complex chronic disease exhibiting features of the metabolic syndrome. ResultsThe study was funded in 2019. Enrollment has commenced and is expected to be completed by June 2022. Data collection and follow up are expected to be completed by December 2022. Results from the analyses based on primary outcomes are expected to be submitted for publication by June 2023. ConclusionsThe study will test the implementation of a health technology–assisted lifestyle intervention in a tertiary outpatient setting for a diverse group of patients with complex chronic conditions. It is novel in that it embeds patient choice into intervention exposure and will inform health service decision-makers in regards to the feasibility of scale and spread of technology-assisted access to care for a broader reach of specialist services. Trial RegistrationAustralian New Zealand Clinical Trial Registry ACTRN12620001282976; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378337 International Registered Report Identifier (IRRID)DERR1-10.2196/37556

Abstract Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and strongly correlates with the growing incidence of obesity and type II diabetes. We have developed a human-on-a-chip model composed of human hepatocytes and adipose tissue chambers capable of modeling the metabolic factors that contribute to liver disease development and progression, and evaluation of the therapeutic metformin. This model uses a serum-free, recirculating medium tailored to represent different human metabolic conditions over a 14-day period. The system validated the indirect influence of adipocyte physiology on hepatocytes that modeled important aspects of NAFLD progression, including insulin resistant biomarkers, differential adipokine signaling in different media and increased TNF-α-induced steatosis observed only in the two-tissue model. This model provides a simple but unique platform to evaluate aspects of an individual factor’s contribution to NAFLD development and mechanisms as well as evaluate preclinical drug efficacy and reassess human dosing regimens.

Based on extensive herbarium, field, botanical illustration, and molecular phylogenetic research, five genera and eight species are recognised for the Neotropical Haemodoraceae. New taxa include Cubanicula Hopper et al., Xiphidium pontederiiflorum M.Pell. et al. and Schiekia timida M.Pell. et al. Two new combinations are made, Cubanicula xanthorrhiza (C.Wright ex Griseb.) Hopper et al. and Schiekia silvestris (Maas & Stoel) Hopper et al. We also correct the author citation for Xiphidium, provide the necessary typifications for several names and present an updated identification key, comments, and photo plates for all species. Finally, we provide high-quality illustrations for most of the recognised species and their diagnostic characters.

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease in Australia and its recent increase mirrors the obesity and type 2 diabetes epidemics. Currently, many patients who present to primary care with abnormal liver function tests or steatosis on liver ultrasound are referred for assessment in secondary care. Due to the large number of patients with NAFLD, this results in long waits for clinical and fibrosis assessment, placing unnecessary burden on the public hospital system. Methods We will conduct a 1:1 parallel randomised trial to compare two alternative models of care for NAFLD. Participants will be randomised to usual care or the LOCal Assessment and Triage Evaluation (LOCATE) model of care and followed for 1 year. We will recruit patients from the non-neighbouring Sunshine Coast and Metro South Hospital and Health Services (HHSs) in Queensland, Australia. Our primary outcome of interest is time to diagnosis of high-risk NAFLD, based on the number of participants in each arm of the study who receive a diagnosis of clinically significant fibrosis. Two hundred and 34 participants will give us a 95% power to detect a 50% reduction in the primary outcome of time to diagnosis of high-risk disease. We will also conduct an economic evaluation, evaluating the cost-effectiveness of the new model of care. We will also evaluate the implementation of the new model of care. Discussion It is anticipated that the results of this study will provide valuable new information regarding the management of NAFLD in the Australian setting. A relatively simple change to care could result in earlier identification of patients with significant liver disease and lower overall costs for the health system. Results will be directly disseminated to key staff for further distribution to consumers, policy- and decision-makers in the form of evidence briefs, plain language summaries and policy recommendations. Trial registration The trial was registered on 30 January, 2020 and can be found via ANZCTR - number ACTRN12620000158965 .

Advancements in 16S rRNA gene amplicon community sequencing have vastly expanded our understanding of the reproductive microbiome and its role in fertility. In humans, Lactobacillus is the overwhelmingly dominant bacteria within reproductive tissues and is known to be commensal and an indicator of fertility in women and men. It is also known that Lactobacillus is not as largely abundant in the reproductive tissues of domestic livestock species. Thus, the objective of this review is to summarize the research to date on both female and male reproductive microbiomes in domestic livestock species (i.e., dairy cattle, beef cattle, swine, small ruminants, and horses). Having a comprehensive understanding of reproductive microbiota and its role in modulating physiological functions will aid in the development of management and therapeutic strategies to improve reproductive efficiency.

The transition areas between different tissues, known as tissue interfaces, have limited ability to regenerate after damage, which can lead to incomplete healing. Previous studies focussed on single interfaces, most commonly bone-tendon and bone-cartilage interfaces. Herein, we develop a 3D in vitro model to study the regeneration of the bone-tendon-muscle interface. The 3D model was prepared from collagen and agarose, with different concentrations of hydroxyapatite to graduate the tissues from bones to muscles, resulting in a stiffness gradient. This graduated structure was fabricated using indirect 3D printing to provide biologically relevant surface topographies. MG-63, human dermal fibroblasts, and Sket.4U cells were found suitable cell models for bones, tendons, and muscles, respectively. The biphasic and triphasic hydrogels composing the 3D model were shown to be suitable for cell growth. Cells were co-cultured on the 3D model for over 21 days before assessing cell proliferation, metabolic activity, viability, cytotoxicity, tissue-specific markers, and matrix deposition to determine interface formations. The studies were conducted in a newly developed growth chamber that allowed cell communication while the cell culture media was compartmentalised. The 3D model promoted cell viability, tissue-specific marker expression, and new matrix deposition over 21 days, thereby showing promise for the development of new interfaces.

Myasthenia gravis (MG) is a chronic and progressive neuromuscular disease where autoantibodies target essential proteins such as the nicotinic acetylcholine receptor (nAChR) at the neuromuscular junction (NMJ) causing muscle fatigue and weakness. Autoantibodies directed against nAChRs are proposed to work by three main pathological mechanisms of receptor disruption: blocking, receptor internalization, and downregulation. Current in vivo models using experimental autoimmune animal models fail to recapitulate the disease pathology and are limited in clinical translatability due to disproportionate disease severity and high animal death rates. The development of a highly sensitive antibody assay that mimics human disease pathology is desirable for clinical advancement and therapeutic development. To address this lack of relevant models, an NMJ platform derived from human iPSC differentiated motoneurons and primary skeletal muscle was used to investigate the ability of an anti-nAChR antibody to induce clinically relevant MG pathology in the serum-free, spatially organized, functionally mature NMJ platform. Treatment of the NMJ model with the anti-nAChR antibody revealed decreasing NMJ stability as measured by the number of NMJs before and after the synchrony stimulation protocol. This decrease in NMJ stability was dose-dependent over a concentration range of 0.01–20 μg/mL. Immunocytochemical (ICC) analysis was used to distinguish between pathological mechanisms of antibody-mediated receptor disruption including blocking, receptor internalization and downregulation. Antibody treatment also activated the complement cascade as indicated by complement protein 3 deposition near the nAChRs. Additionally, complement cascade activation significantly altered other readouts of NMJ function including the NMJ fidelity parameter as measured by the number of muscle contractions missed in response to increasing motoneuron stimulation frequencies. This synchrony readout mimics the clinical phenotype of neurological blocking that results in failure of muscle contractions despite motoneuron stimulations. Taken together, these data indicate the establishment of a relevant disease model of MG that mimics reduction of functional nAChRs at the NMJ, decreased NMJ stability, complement activation and blocking of neuromuscular transmission. This system is the first functional human in vitro model of MG to be used to simulate three potential disease mechanisms as well as to establish a preclinical platform for evaluation of disease modifying treatments (etiology).

Diabetic myopathy is a co-morbidity diagnosed in most diabetes mellitus patients, yet its pathogenesis is still understudied, which hinders the development of effective therapies. This project aimed to investigate the effect of hyperglycemia on human myoblast physiology, devoid of other complicating factors, by utilizing human myoblasts derived from induced pluripotent stem cells (iPSCs), in a defined in vitro system. IPSC-derived myoblasts were expanded under three glucose conditions: low (5 mM), medium (17.5 mM) or high (25 mM). While hyperglycemic myoblasts demonstrated upregulation of Glut4 relative to the euglycemic control, myoblast proliferation demonstrated a glucose dose-dependent impedance. Further cellular analysis revealed a retarded cell cycle progression trapped at the S phase and G2/M phase and an impaired mitochondrial function in hyperglycemic myoblasts. Terminal differentiation of these hyperglycemic myoblasts resulted in significantly hypertrophic and highly branched myotubes with disturbed myosin heavy chain arrangement. Lastly, functional assessment of these myofibers derived from hyperglycemic myoblasts demonstrated comparatively increased fatigability. Collectively, the hyperglycemic myoblasts demonstrated deficient muscle regeneration capability and functionality, which falls in line with the sarcopenia symptoms observed in diabetic myopathy patients. This human-based iPSC-derived skeletal muscle hyperglycemic model provides a valuable platform for mechanistic investigation of diabetic myopathy and therapeutic development.

Background. Rapid excess weight gain and metabolic complications contribute to poor outcomes following liver transplant care. Providing specialist lifestyle intervention with equitable access is a challenge for posttransplant service delivery. Methods. This study investigated the feasibility of a 12-wk telehealth delivered lifestyle intervention for liver transplant recipients (randomized controlled trial with a delayed intervention control group). The intervention included 14 group sessions facilitated by nutrition and exercise specialists via video streaming telehealth and participants used their own devices. Feasibility was assessed across session attendance, the adequacy, acceptability, and confidence with the telehealth technology and adherence to diet (Mediterranean Diet Adherence Score). Secondary pooled analysis of effectiveness was determined from changes in quality of life and metabolic syndrome severity score. Results. Of the 35 participants randomized, dropout was 22.8% (n = 8) and overall session attendance rate was 60%. Confidence with and adequacy of home technology was rated high in 96% and 91% of sessions, respectively. Participants randomized to the intervention significantly improved Mediterranean Diet Adherence Score (2-point increase [95% confidence interval, 1.5-3.4] versus control 0 point change [95% confidence interval, –1.4 to 1.2]; P = 0.004). Intervention (within group) analysis found the intervention significantly decreased the metabolic syndrome severity score (–0.4 [95% confidence interval, –0.6 to –0.1] P = 0.01), and improved mental health-related quality of life (2.5 [95% confidence interval, 0.4-4.6] P = 0.03). Conclusions. A cardioprotective lifestyle intervention delivered via telehealth is feasible for liver transplant recipients and may improve access to specialist care to support metabolic health and wellness after transplant.