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Association between frailty and physical function recovery of people who received physiotherapy early rehabilitation during acute hospitalisation: An observational cohort study
OBJECTIVES: Examine the effect of frailty on physical function recovery in people admitted to hospital who received a physiotherapy Early Rehabilitation program. METHODS: Observational cohort (1 January 2021 to 31 December 2021). Patients admitted to the acute site at Austin Health, Australia who received an Early Rehabilitation program (targeted physical rehabilitation to address goals aligned to physiotherapy intervention in parallel with acute medical treatment) were eligible. Frailty was measured with the Clinical Frailty Scale (CFS). The primary outcome was, across the CFS, magnitude of change from admission to discharge in physical function assessed with the modified Iowa Level of Assistance Scale (mILOA). Secondary outcomes were length of stay and discharge destination. Generalised additive models were used. RESULTS: There were 674 patients included in the study. Irrespective of frailty status, mean improvement in physical function from admission to discharge exceeded the minimal datable change of 5.8 points for the mILOA. Larger average improvements in mILOA were observed in patients with lower degrees of frailty (p < 0.001 overall effect), where a portion of patients with severe frailty did not make clinically meaningful gains in physical function following Early Rehabilitation. Mean improvement in physical function and predicted probabilities for discharge home were similar; where greater frailty severity was associated with a lesser chance of going home at acute hospital discharge (p = 0.002 overall effect). CONCLUSIONS: Validating the link between predictions for change in physical function and discharge home in people receiving early rehabilitation during acute hospitalisation would be of great clinical utility
Gut Microbiota Features in Relation to Fecal Microbiota Transplantation Outcome in Ulcerative Colitis: A Systematic Review and Meta-Analysis
BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) can induce remission in patients with ulcerative colitis, yet its efficacy needs improvement. We conducted a comprehensive evaluation of the current literature on microbial factors affecting outcome, as well as a meta-analysis on some of the largest datasets regarding composition. METHODS: MEDLINE, Embase, and Cochrane were systematically searched through August 2024 for relevant studies. The quality of studies was analyzed with JBI tools and a composite critical appraisal score. Additionally, species-level data from 2 landmark FMT trials (the Transplantation of Feces in Ulcerative Colitis; Returning Nature's Homeostasis [TURN] and Fecal Microbiota Transplantation for Chronic Active Ulcerative Colitis [FOCUS] trials) were reanalyzed from a compositional perspective. RESULTS: Out of 3755 citations identified, 56 met the inclusion criteria, of which 29 fulfilled quality standards. Higher microbial α-diversity, either in donors or recipients (at baseline or following FMT treatment), was associated with better clinical response rates. Engraftment of the donors' microbiota could not be clearly linked with clinical response, possibly because not every donor has an ideal microbiome. Butyrate-producing species from the Lachnospiraceae and Oscillospiraceae families were often related with response, whereas the reverse was true for Fusobacteria, many Proteobacteria, and Ruminococcus gnavus. Compositional analyses showed that clinical response is associated with a shift from a low-diversity, often Bacteroides-dominant composition to one with higher diversity, either dominated by various butyrate producers, the Christensenellaceae-Methanobrevibacter trophic network, or a moderate/high-diversity composition with abundant but not excessive levels of Prevotella copri. CONCLUSIONS: This systematic review/meta-analysis yielded a coherent picture from a compositional perspective, which may help identify beneficial donor profiles and guide personalized FMT approaches
487. Prebiotics rescue gut microbiome dysregulation and enhance cognitive and gastrointestinal function in a mouse model of schizophrenia
Abstract
Background
Schizophrenia is a devastating psychiatric disorder characterized by positive (e.g. hallucinations) and negative (e.g. reduced motivation) symptoms, and cognitive deficits. Chronic gastrointestinal tract issues exist as comorbid symptoms of schizophrenia. Recent findings indicate the involvement of the microorganisms that inhabit the gut, the microbiota (and the broader microbiome which also includes microbial genomes, etc.) in schizophrenia pathogenesis. Prior discoveries by our group and others have established the metabotropic glutamate receptor 5 (mGlu5) knockout mice as a useful preclinical model of schizophrenia. We have provided evidence of strong face validity with respect to schizophrenia-like endophenotypes, and predictive validity in response to the antipsychotic drug clozapine. We have also previously discovered altered gut microbiota (gut dysbiosis) in this preclinical model of schizophrenia, providing the first evidence of such dysbiosis in any genetic animal model of schizophrenia. This gut dysbiosis exhibits parallels to microbiome profiling reported in clinical studies of schizophrenia, further supporting the validity of this preclinical model.
Aims & Objectives
We followed up our discovery of gut dysbiosis in this preclinical model with interventions designed to correct the abnormalities in the gut microbiota. We hypothesised that amelioration of gut dysbiosis would be associated with therapeutic effects on schizophrenia-like endophenotypes in this validated mouse model. In the present study, we hypothesized that chronic administration with prebiotics fructooligosaccharide and galactooligosaccharide (FOS and GOS; a combination used clinically for other disorders) would restore gut microbiome composition of the mGlu5 knockout mouse model of schizophrenia, which we previously demonstrated to exhibit gut dysbiosis.
Method
We assessed the impact of prebiotics on gut microbiome composition and function, as well as the gastrointestinal function and schizophrenia-like phenotype of mGlu5 knockout mice and wildtype littermates. We administered a combination of the prebiotics FOS and GOS, versus vehicle control administration, in both the mouse model of schizophrenia and wildtype littermates. Mice were administered a combination of FOS and GOS (dissolved in drinking water for 0.3-0.4 g/mouse/day) or water from 6 to 14 weeks of age. Duration of treatment and dose of prebiotics were chosen based on previous studies in rodents that showed modulation of the gut microbiome, behavioural outcomes and neurochemical effects. This was followed by detailed investigations of gut and brain function, including extensive behavioural profiling.
Results
The present study firstly corroborated the altered gut microbiome composition in the mGlu5 KO mouse model of schizophrenia. Importantly we have revealed an altered microbial metabolic profile. We have also shown that the prebiotics we administered were not only able to rescue these gut microbiome changes but furthermore had additional beneficial effects including cognitive enhancement and improved gastrointestinal function. We were able to show, in two independent tests, a promising effect of prebiotics on cognition.
Discussion & Conclusions
These preclinical findings indicate that prebiotics, such as the combination of FOS and GOS used in the present study, may have therapeutic potential in schizophrenia as an add-on intervention with an exceptional safety profile. Future studies will explore the utility of such prebiotic interventions in other preclinical models, with the ultimate aim to translate these novel findings to clinical trials
Modelling the joint effects of single occupancy and N95 respirators on COVID-19 outbreaks in hospital wards
BACKGROUND: Outbreaks of respiratory pathogens on hospital wards present challenges for control of hospital-acquired infections. AIM: To investigate the potential for synergistic effects between structural controls (single-occupancy patient rooms) and routine precautions (use of N95 respirators by healthcare staff), in preventing and mitigating outbreaks of airborne pathogens on hospital wards. METHODS: This study applied an agent-based extension of the Wells-Riley model of airborne pathogen exposure to simulate COVID-19 outbreaks on hospital wards. Secondary attack rates and the sizes of outbreaks resulting from introduction of unrecognized cases in hospital wards with double- or single-occupancy patient rooms were simulated. The impact of N95 respirator use by nurses during patient care activities was simulated, assuming an efficacy of 90% for protection and source control. FINDINGS: The size of simulated outbreaks recorded at day 14 was markedly lower in wards with only single-occupancy rooms, compared to double-occupancy rooms (with means of 14.1 and 22.8 infections, respectively). Nurses were more likely to acquire infection than patients for both single- and double-occupancy scenarios. Single occupancy was associated with smaller outbreak sizes, with a larger relative impact on patients than on staff. N95 respirators were effective at mitigating outbreaks, with higher impacts in wards with single-occupancy patient rooms. CONCLUSION: Our results are consistent with claims that single-occupancy patient rooms reduce transmission of SARS-CoV-2 on hospital wards. Our findings also support the claim that use of N95 respirators by nurses when caring for patients can reduce the effective reproductive ratio of the pathogen. Finally, we demonstrated that switching to single occupancy can increase the benefit of N95 respirator use by healthcare staff
Management of patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplantation: position statement of the Medical and Scientific Advisory Group of Myeloma Australia
The survival of newly diagnosed patients with multiple myeloma has improved significantly over the past 20 years with significant therapeutic advances. Despite this, high-dose chemotherapy followed by autologous stem cell transplantation remains the standard of care in newly diagnosed patients who are considered transplant eligible. Here, we summarise the recommendations of the Medical and Scientific Advisory Group of Myeloma Australia for patients considered suitable for high-dose chemotherapy and autologous stem cell transplantation as part of the initial therapy
Performance Evaluation of the Quantification of Cement Microphases Using Energy Dispersive X-ray Spectroscopy Imaging
Abstract
Cement manufacturing is one of the widest industries in the world and yet largely contributes to the global CO2 emissions. As a result, introducing low carbon sustainable concrete designs without compromising performance has become one of the greatest challenges over the last few decades. This complexity was majorly caused by heterogeneity of concrete due to the existence of cementitious particles, fibers, or fine filler materials. Further, this multi-scale material heterogeneity of concrete influences the performance of concrete at macro levels and makes it more complicated to understand the hydration behaviors. Macroscale trial and error-based mechanical property testing might not always be the feasible way to find the optimum mix designs, because those techniques cannot quantify the root cause relationship to the microstructure. Therefore, microscale quantitative chemical and mechanical characterizations pave the way for cement to upscale strength from microlevel to structural level using strength homogenization, revealing the compositional characteristics which contributed to the strength variation in any novel cement mix. Since microphase identification is crucial to achieve that task, in this study, energy-dispersive x-ray spectroscopy (EDS) together with scanning electron microscopy (SEM) is used to quantify the hydration of an ultra-high-performance cement paste at microlevel. The image analysis is carried out using the mapping data collected from four different locations of the same cement batch, and the accuracy of the hydration quantification is compared with an independent analytical hydration simulation software, Virtual Cement and Concrete Testing Laboratory (VCCTL) by NIST
First molecular phylogeny of mycoparasitic species of Sphaerellopsis isolated from rust fungi in Australia
Abstract
Three species, Sphaerellopsis filum, S. macroconidialis, and S. paraphysata, from Queensland and Victoria, Australia, were identified and characterised by multilocus sequence analyses. This study clarifies earlier reports of Sphaerellopsis in Australia and provides the first report of S. filum in Australia. We also confirm the presence of S. macroconidialis and S. paraphysata in Australia. A single-locus phylogeny based on the internal transcribed spacer (ITS) region of the ribosomal DNA (rDNA) provided sufficient resolution for species-level identification and yielded a topology consistent with that of the combined dataset of ITS, large subunit of the rDNA, and the RNA polymerase II second largest subunit. The high intron variability in the translation elongation factor 1-α region among Sphaerellopsis spp. made it unsuitable for phylogenetic analysis. The specimens and data generated here lay the groundwork for future studies into the evolution and molecular basis of mycoparasitism in Sphaerellopsis
The Human Cardiac “Age-OME”: Age-Specific Changes in Myocardial Molecular Expression
Ageing is one of the most significant risk factors for heart disease; however, it is still not clear how the human heart changes with age. Taking advantage of a unique set of pre-mortem, cryopreserved, non-diseased human hearts, we performed omics analyses (transcriptomics, proteomics, metabolomics, and lipidomics), coupled with biologically informed computational modelling in younger (≤ 25 years old) and older hearts (≥ 50 years old) to describe the molecular landscape of human cardiac ageing. In older hearts, we observed a downregulation of proteins involved in calcium signalling and the contractile apparatus. Furthermore, we found a potential dysregulation of central carbon generation of fuel, glycolysis, and fatty acids oxidation, along with an increase in long-chain fatty acids. This study presents and analyses the first molecular data set of normal human cardiac ageing, which has relevant implications for understanding the human cardiac ageing process and the development of age-related heart disease
Chronic outcomes after mild-moderate traumatic brain injury in adult seizure-prone (FAST) and seizure-resistant (SLOW) rats: A model for understanding genetic contributions to acquired epileptogenesis?
Post-traumatic epilepsy (PTE) is a common, serious, long-term complication of traumatic brain injury (TBI). However, only a minority of individuals will develop epilepsy after a TBI, and the contribution of genetic predisposition to the risk of acquired epilepsy warrants further exploration. In this study, we examined whether innate, genetically determined differences in seizure susceptibility between seizure-prone FAST and seizure-resistant SLOW rat strains would influence chronic behavioral and PTE outcomes after experimental TBI. We hypothesized that FAST rats would show increased vulnerability to PTE and poorer neurobehavioral outcomes. Using the lateral fluid percussion injury model, we first determined the optimal injury parameters to generate a mild-moderate TBI in young adult FAST rats, which had previously shown high mortality to severe TBI. Then, FAST and SLOW rats underwent TBI or sham surgery, and a series of behavioral tests were performed either acutely (within 4 weeks) or chronically (more than 22 weeks) post-injury. Acutely, FAST rats showed an increased physiological response to TBI with a longer apnea duration, delayed pain response, and delayed self-righting, as well as increased acute seizure-like behavior compared to SLOW rats. Conversely, SLOW rats showed greater neuromotor deficits and weight loss sub-acutely compared to FAST rats. Chronically, while strain-specific phenotypes were observed (e.g., FAST rats showing increased anxiety-like behavior, altered nociceptive responses, and polydipsia), no TBI effects were detected. Analysis of continuous video-electroencephalographic recordings over a 1-month period starting at 6 months post-TBI did not reveal any spontaneous seizures. However, periodic epileptiform discharges were only found in FAST rats that had a TBI. Together, these findings reflect fundamental differences in chronic behavior and epileptiform discharges as a result of innate distinctions in epileptogenic susceptibility in FAST versus SLOW rats. However, a lack of spontaneous seizure activity or chronic neurobehavioral deficits in TBI animals confounded our ability to address the initial hypothesis, such that alternative injury models may be more suitable to study genetic contributions to the development of PTE
BYOD use and perception among hospital clinicians – A qualitative study
Background: The increasing trend of healthcare professionals using personal devices for work, termed Bring-Your-Own-Device (BYOD), is becoming prevalent in hospitals. Despite its growing importance, there is limited empirical research addressing the real-world experiences of clinicians in using BYOD. Objective: This study seeks to explore clinicians' perception and behavior with respect to BYOD use in Australian hospitals, focusing on socio-technical aspects and its impact on clinical and administrative work. Methods: Fourteen semi-structured interviews were conducted with clinicians in Australian hospitals. The framework method was applied to perform a thematic analysis, identifying key socio-technical themes related to BYOD usage. Results: Clinicians reported using BYOD for various tasks, with smartphones being the most preferred device over tablets or laptops. While smartphones were favored for their convenience, laptops were used for complex tasks like viewing radiological images, and tablets were rarely utilized. The multifunctionality and convergence of BYOD devices were seen as facilitators for mobility and productivity, contributing to cost and time savings. However, significant barriers were identified, including increased risks of patient information leaks, challenges in maintaining work-life balance, and concerns about hospital-acquired infections. The study also found that doctors rated BYOD highly for its efficiency across various settings, while nurses experienced more issues with distractions and boundary management. Allied health professionals' use varied by specialty. Conclusion: Findings from the study provide crucial insights into the advantages and challenges of BYOD usage in hospitals. These insights can help shape policies and management strategies to support secure and effective BYOD practices in healthcare settings