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Item Metadata only Antimicrobial and healing promoting properties of animal and plant oils for treatment of infected wounds(Cambridge Media, 2019) Tahlia, K.; Mashtoub, S.; Howarth, G.; Allison, C.; Kopecki, Z.Chronic wounds are a serious medical problem both in the hospital and community setting. The healing of chronic wounds is often compromised by colonisation of different bacterial pathogens leading to life-threatening infections. Bacterial infections are a critical contributing factor to chronic wounds and can lead to biofilm formation and inhibition of innate inflammatory responses, including the reduction of acute inflammation. Concerningly, the overuse of systemic antibiotics and the use of traditional therapeutics, including topical antimicrobials – iodine, chlorhexidine and silver – have both greatly contributed to the development of a global increase in antimicrobial resistance. This has therefore led to a renewed interest in natural and alternative antimicrobial treatment strategies in wound care for the treatment of infected wounds. This review summarises the pre-clinical and clinical evidence that exists for the use of natural remedies, namely essential and animal oils, as adjunctive therapeutic approaches for the treatment of infected wounds. It also discusses novel approaches in nanotechnology that are being used for the development of natural remedies aimed at improving the healing of infected chronic wounds.Item Metadata only A new method to measure aquaporin-facilitated membrane diffusion of hydrogen peroxide and cations in plant suspension cells(Wiley, 2024) Ahmed, J.; Ismail, A.; Ding, L.; Yool, A.J.; Chaumont, F.Plant aquaporins (AQPs) facilitate the membrane diffusion of water and small solutes, including hydrogen peroxide (H2 O2 ) and, possibly, cations, essential signalling molecules in many physiological processes. While the determination of the channel activity generally depends on heterologous expression of AQPs in Xenopus oocytes or yeast cells, we established a genetic tool to determine whether they facilitate the diffusion of H2 O2 through the plasma membrane in living plant cells. We designed genetic constructs to co-express the fluorescent H2 O2 sensor HyPer and AQPs, with expression controlled by a heat shock-inducible promoter in Nicotiana tabacum BY-2 suspension cells. After induction of ZmPIP2;5 AQP expression, a HyPer signal was recorded when the cells were incubated with H2 O2 , suggesting that ZmPIP2;5 facilitates H2 O2 transmembrane diffusion; in contrast, the ZmPIP2;5W85A mutated protein was inactive as a water or H2 O2 channel. ZmPIP2;1, ZmPIP2;4 and AtPIP2;1 also facilitated H2 O2 diffusion. Incubation with abscisic acid and the elicitor flg22 peptide induced the intracellular H2 O2 accumulation in BY-2 cells expressing ZmPIP2;5. We also monitored cation channel activity of ZmPIP2;5 using a novel fluorescent photo-switchable Li+ sensor in BY-2 cells. BY-2 suspension cells engineered for inducible expression of AQPs as well as HyPer expression and the use of Li+ sensors constitute a powerful toolkit for evaluating the transport activity and the molecular determinants of PIPs in living plant cells.Item Open Access Repetitive paired-pulse TMS increases motor cortex excitability and visuomotor skill acquisition in young and older adults(Oxford University Press (OUP), 2023) Hand, B.J.; Merkin, A.; Opie, G.M.; Ziemann, U.; Semmler, J.G.Transcranial magnetic stimulation (TMS) over primary motor cortex (M1) recruits indirect (I) waves that can be modulated by repetitive paired-pulse TMS (rppTMS). The purpose of this study was to examine the effect of rppTMS on M1 excitability and visuomotor skill acquisition in young and older adults. A total of 37 healthy adults (22 young, 18-32 yr; 15 older, 60-79 yr) participated in a study that involved rppTMS at early (1.4 ms) and late (4.5 ms) interstimulus intervals (ISIs), followed by the performance of a visuomotor training task. M1 excitability was examined with motor-evoked potential (MEP) amplitudes and short-interval intracortical facilitation (SICF) using posterior-anterior (PA) and anterior-posterior (AP) TMS current directions. We found that rppTMS increased M1 excitability in young and old adults, with the greatest effects for PA TMS at the late ISI (4.5 ms). Motor skill acquisition was improved by rppTMS at an early (1.4 ms) but not late (4.5 ms) ISI in young and older adults. An additional study using a non-I-wave interval (3.5 ms) also showed increased M1 excitability and visuomotor skill acquisition. These findings show that rppTMS at both I-wave and non-I-wave intervals can alter M1 excitability and improve visuomotor skill acquisition in young and older adults.Item Metadata only Prophylactic probiotics for cancer therapy-induced diarrhoea: A meta-analysis(Lippincott, Williams & Wilkins, 2018) Wardill, H.R.; Van Sebille, Y.Z.A.; Ciorba, M.A.; Bowen, J.M.PURPOSE OF REVIEW: Strong preclinical data support prophylactic probiotics as an effective preventive strategy for diarrhoea secondary to anticancer therapies. To determine the composite evidence that this approach translates to the clinic, we performed a meta-analysis of randomized controlled trials (RCTs) of prophylactic probiotics for the prevention of cancer therapy-induced diarrhoea. RECENT FINDINGS: A three-step search strategy was used to identify relevant studies (1 June 2000-1 June 2017) investigating probiotic intervention for diarrhoea secondary to any cancer therapy (cytotoxic, targeted and immunotherapies). RCTs across PubMed, Embase, CINAHL and CENTRAL were assessed for eligibility and assessed using RevMan 5.3 (The Cochrane Collaboration). Seven trials with a total of 1091 patients were included in this meta-analysis. Compared with placebo, prophylactic probiotics did not prevent or reduce the overall incidence of diarrhoea or severe CTCAE Grade at least 3 diarrhoea [relative risk (RR) = 0.81, 95% confidence interval (95% CI) = 0.60-1.09, Z = 1.41, P = 0.16; RR = 0.54, 95% CI = 0.25-1.16, Z = 1.58, P = 0.11], nor did it influence the use of rescue medication (RR = 0.93, 95% CI = 0.53-1.65, Z = 0.24, P = 0.81). SUMMARY: Current evidence does not support widespread implementation of probiotics for diarrhoea secondary to cytotoxic therapy and the tyrosine kinase inhibitor, dacomitinib. Research efforts should be diverted to pair specific forms of gastrointestinal toxicity and their unique microbial phenotype to develop the ideal microbial protectant.Item Metadata only GABA concentration in sensorimotor cortex following high-intensity exercise and relationship to lactate levels(Wiley, 2018) Coxon, J.P.; Cash, R.F.H.; Hendrikse, J.J.; Rogasch, N.C.; Stavrinos, E.; Suo, C.; Yücel, M.KEY POINTS:Magnetic resonance spectroscopy was conducted before and after high-intensity interval exercise. Sensorimotor cortex GABA concentration increased by 20%. The increase was positively correlated with the increase in blood lactate. There was no change in dorsolateral prefrontal cortex. There were no changes in the glutamate-glutamine-glutathione peak. ABSTRACT: High-intensity exercise increases the concentration of circulating lactate. Cortical uptake of blood borne lactate increases during and after exercise; however, the potential relationship with changes in the concentration of neurometabolites remains unclear. Although changes in neurometabolite concentration have previously been demonstrated in primary visual cortex after exercise, it remains unknown whether these changes extend to regions such as the sensorimotor cortex (SM) or executive regions such as the dorsolateral prefrontal cortex (DLPFC). In the present study, we explored the acute after-effects of high-intensity interval training (HIIT) on the concentration of gamma-Aminobutyric acid (GABA) and the combined glutamate-glutamine-glutathione (Glx) spectral peak in the SM and DLPFC, as well as the relationship with blood lactate levels. Following HIIT, there was a robust increase in GABA concentration in the SM, as evident across the majority of participants. This change was not observed in the DLPFC. Furthermore, the increase in SM GABA was positively correlated with an increase in blood lactate. There were no changes in Glx concentration in either region. The observed increase in SM GABA concentration implies functional relevance, whereas the correlation with lactate levels may relate to the metabolic fate of exercise-derived lactate that crosses the blood-brain barrier.Item Open Access Modulation of dorsal premotor cortex differentially influences I‐wave excitability in primary motor cortex of young and older adults(Wiley, 2023) Liao, W.; Opie, G.M.; Ziemann, U.; Semmler, J.G.Previous research using transcranial magnetic stimulation (TMS) has demonstrated weakened connectivity between dorsal premotor cortex (PMd) and motor cortex (M1) with age. While this alteration is probably mediated by changes in the communication between the two regions, the effect of age on the influence of PMd on specific indirect (I) wave circuits within M1 remains unclear. The present study therefore investigated the influence of PMd on early and late I-wave excitability inM1of young and older adults. Twenty-two young (mean±SD, 22.9±2.9 years) and 20 older (66.6 ± 4.2 years) adults participated in two experimental sessions involving either intermittent theta burst stimulation (iTBS) or sham stimulation over PMd. Changes within M1 following the intervention were assessed with motor-evoked potentials (MEPs) recorded from the right first dorsal interosseous muscle. We applied posterior–anterior (PA) and anterior–posterior (AP) current single-pulse TMS to assess corticospinal excitability (PA1mV; AP1mV; PA0.5mV, early; AP0.5mV, late), and paired-pulse TMS short intracortical facilitation for I-wave excitability (PA SICF, early; AP SICF, late). Although PMd iTBS potentiated PA1mV and AP1mV MEPs in both age groups (both P < 0.05), the time course of this effect was delayed for AP1mV in older adults (P = 0.001). Furthermore, while AP0.5mV, PA SICF and AP SICF were potentiated in both groups (all P < 0.05), potentiation of PA0.5mV was only apparent in young adults (P < 0.0001).While PMd influences early and late I-wave excitability in young adults, direct PMdmodulation of the early circuits is specifically reduced in older adults.Item Open Access Blood flow rates to leg bones of extinct birds indicate high levels of cursorial locomotion(Cambridge University Press (CUP), 2023) Hu, Q.; Miller, C.V.; Snelling, E.P.; Seymour, R.S.Foramina of bones are beginning to yield more information about metabolic rates and activity levels of living and extinct species. This study investigates the relationship between estimated blood flow rate to the femur and body mass among cursorial birds extending back to the Late Cretaceous. Data from fossil foramina are compared with those of extant species, revealing similar scaling relationships for all cursorial birds and supporting crown bird–like terrestrial locomotor activity. Because the perfusion rate in long bones of birds is related to the metabolic cost of microfracture repair due to stresses applied during locomotion, as it is in mammals, this study estimates absolute blood flow rates from sizes of nutrient foramina located on the femur shafts. After differences in body mass and locomotor behaviors are accounted for, femoral bone blood flow rates in extinct species are similar to those of extant cursorial birds. Femoral robustness is generally greater in aquatic flightless birds than in terrestrial flightless and ground-dwelling flighted birds, suggesting that the morphology is shaped by life-history demands. Femoral robustness also increases in larger cursorial bird taxa, probably associated with their weight redistribution following evolutionary loss of the tail, which purportedly constrains femur length, aligns it more horizontally, and necessitates increased robustness in larger species.Item Metadata only Subjective responses to wind farm noise: A review of laboratory listening test methods(Elsevier, 2019) Alamir, M.A.; Hansen, K.L.; Zajamsek, B.; Catcheside, P.Laboratory listening tests are a fundamental part of identifying and quantifying human perceptual responses to noise, including wind farm noise (WFN); a low-frequency environmental noise with time-varying components with the potential to impact more people as wind farm facilities continue to expand worldwide. Design characteristics of WFN listening tests vary between studies. This likely impacts WFN listening test results and makes quantitative comparisons difficult between studies. Accordingly, this paper reviews the available literature regarding WFN listening test methods, their overall characteristics and potentially important differences in noise stimuli and rating methods used. The key design variables explored include participant selection, stimuli duration, signal synthesis methods, noise reproduction methods and listening room characteristics. Listening test results from studies that have investigated the perceptual effects of various WFN components such as lowfrequency noise and infrasound, tonality and amplitude modulation are presented. The impact on listening tests of factors unrelated to noise such as sensory acuity and sensitivity, attitudes/beliefs and visual effects are also explored. It is shown that some WFN characteristics have received limited attention to date in listening tests. These include broadband low-frequency noise, tonal noise, tonal amplitude modulation and amplitude modulation parameters such as modulation frequency and intermittency. The relative importance of acoustic and non-acoustic factors to human perception is also largely unknown and requires well-designed listening tests to help elucidate.Item Metadata only Endothelium-dependent relaxation is impaired in Schlager hypertensive (BPH/2J) mice by region-specific mechanisms in conductance and resistance arteries(Elsevier BV, 2023) Jelinic, M.; Jackson, K.L.; O'Sullivan, K.; Singh, J.; Giddy, T.; Deo, M.; Parry, L.J.; Ritchie, R.H.; Woodman, O.L.; Head, G.A.; Leo, C.H.; Qin, C.X.Aims: Endothelial dysfunction and arterial stiffness are hallmarks of hypertension, and major risk factors for cardiovascular disease. BPH/2J (Schlager) mice are a genetic model of spontaneous hypertension, but little is known about the vascular pathophysiology of these mice and the region-specific differences between vascular beds. Therefore, this study compared the vascular function and structure of large conductance (aorta and femoral) and resistance (mesenteric) arteries of BPH/2J mice with their normotensive BPN/2J counterparts. Main methods: Blood pressure was measured in BPH/2J and BPN/3J mice via pre-implanted radiotelemetry probes. At endpoint, vascular function and passive mechanical wall properties were assessed using wire and pressure myography, qPCR and histology. Key findings: Mean arterial blood pressure was elevated in BPH/2J mice compared to BPN/3J controls. Endothelium-dependent relaxation to acetylcholine was attenuated in both the aorta and mesenteric arteries of BPH/2J mice, but through different mechanisms. In the aorta, hypertension reduced the contribution of prostanoids. Conversely, in the mesenteric arteries, hypertension reduced the contribution of both nitric oxide and endothelium-dependent hyperpolarization. Hypertension reduced volume compliance in both femoral and mesenteric arteries, but hypertrophic inward remodelling was only observed in the mesenteric arteries of BPH/2J mice. Significance: This is the first comprehensive investigation of vascular function and structural remodelling in BPH/ 2J mice. Overall, hypertensive BPH/2J mice exhibited endothelial dysfunction and adverse vascular remodelling in the macro- and microvasculature, underpinned by distinct region-specific mechanisms. This highlights BPH/ 2J mice as a highly suitable model for evaluating novel therapeutics to treat hypertension-associated vascular dysfunction.Item Open Access Exposure of anti-infective drugs and the dynamic changes of the gut microbiota during gastrointestinal mucositis in autologous stem cell transplant patients: a pilot study(Springer, 2023) Märtson, A.-G.; da Silva Ferreira, A.R.; Veringa, A.; Liu, L.; Wardill, H.R.; Junier, L.A.T.; van der Werf, T.S.; Harmsen, H.J.M.; Sturkenboom, M.G.G.; Span, L.F.; Tissing, W.J.E.; Alffenaar, J.-W.C.Gastrointestinal mucositis could potentially compromise drug absorption due to functional loss of mucosa and other pathophysiological changes in the gastrointestinal microenvironment. Little is known about this effect on commonly used anti-infectives. This study aimed to explore the association between different stages of gastrointestinal mucositis, drug exposure, and gut microbiota. A prospective, observational pilot study was performed in HSCT patients aged ≥ 18 years receiving anti-infectives orally. Left-over blood samples and fecal swabs were collected from routine clinical care until 14 days after HSCT to analyze drug and citrulline concentrations and to determine the composition of the gut microbiota. 21 patients with a median age of 58 (interquartile range 54-64) years were included with 252 citrulline, 155 ciprofloxacin, 139 fluconazole, and 76 acyclovir concentrations and 48 fecal swabs obtained. Severe gastrointestinal mucositis was observed in all patients. Due to limited data correlation analysis was not done for valacyclovir and fluconazole, however we did observe a weak correlation between ciprofloxacin and citrulline concentrations. This could suggest that underexposure of ciprofloxacin can occur during severe mucositis. A follow-up study using frequent sampling rather than the use of left-over would be required to investigate the relationship between gastrointestinal mucositis, drug exposure, and gut microbiome.Item Metadata only Recurrent Motion Neural Network for Low Resolution Drone Detection(IEEE, 2020) Pratt, H.; Evans, B.; Rowntree, T.; Reid, I.; Wiederman, S.; Digital Image Computing: Techniques and Applications (DICTA) (29 Nov 2020 - 2 Dec 2020 : virtual online)Drones are becoming increasingly prevalent in everyday usage with many commercial applications in fields such as construction work and agricultural surveying. Despite their common commercial use, drones have been recently used with malicious intent, such as airline disruptions at Gatwick Airport. With the emerging issue of safety concerns for the public and other airspace users, detecting and monitoring active drones in an area is crucial. This paper introduces a recurrent convolutional neural network (CNN) specifically designed for drone detection. This CNN can detect drones from down-sampled images by exploiting the temporal information of drones in flight and outperforms a state-of-the-art conventional object detector. Due to the lightweight and low resolution nature of this network, it can be mounted on a small processor and run at near real-time speeds.Item Metadata only 5-Fluorouracil Induces an Acute Reduction in Neurogenesis and Persistent Neuroinflammation in a Mouse Model of the Neuropsychological Complications of Chemotherapy(Springer Nature, 2022) Subramaniam, C.B.; Wardill, H.R.; Davies, M.R.; Heng, V.; Gladman, M.A.; Bowen, J.M.The neuropsychological symptoms associated with chemotherapy treatment remain a major challenge with their prevention hampered by insufcient understanding of pathophysiology. While long-term neuroimmune changes have been identifed as a hallmark feature shared by neurological symptoms, the exact timeline of mechanistic events preceding neuroinfammation, and the relationship between the glial cells driving this neuroinfammatory response, remain unclear. We therefore aimed to longitudinally characterize the neuroimmunological changes following systemic 5-fuorouracil (5-FU) treatment to gain insight into the timeline of events preceding the well-documented chronic neuroinfammation seen following chemotherapy. Eighteen female C57Bl/6 mice received a single intraperitoneal dose of 5-FU and groups were killed at days 1 and 2 (acute timepoint), days 4 and 8 (subacute timepoint), and days 16 and 32 (chronic timepoint). A further six mice were administered with vehicle control with tissues collected from three mice on day 1 and day 32 of the study. The expression of key genes of interest, BCL2, BDNF, TIMP1, MMP-9, MMP-2, TNFα, IL-1β, and IL-6R were assessed using real time polymerase chain reaction. Levels of neurogenesis were determined through immunofuorescent staining of doublecortin (DCX). The density of microglia and astrocytes were assessed using immunofuorescence staining of Iba1 and GFAP respectively. 5-FU treatment caused signifcant decreases to DCX staining at acute timepoints (p=0.0030) which was positively correlated with BCL2 expression levels. An increase to microglial density was observed in the prefrontal cortex (p=0.0256), CA3 region (p=0.0283), and dentate gyrus (p=0.0052) of the hippocampus at acute timepoints. 5-FU caused increases to astrocyte density, across multiple brains regions, at subacute and chronic timepoints which were positively correlated with TNFα, TIMP-1, MMP-2, and IL-6R expression. This study has identified acute objective neuroinflammatory changes suggesting that the role of early intervention should be explored to prevent the development of neuropsychological deficits in the longer term following chemotherapy.Item Metadata only Motor cortex plasticity is greater in endurance-trained cyclists following acute exercise(American Physiological Society, 2022) Hand, B.J.; Opie, G.M.; Sidhu, S.K.; Semmler, J.G.Previous research using transcranial magnetic stimulation (TMS) has shown that plasticity within primary motor cortex (M1) is greater in people who undertake regular exercise, and a single session of aerobic exercise can increase M1 plasticity in untrained participants. This study aimed to examine the effect of an acute bout of exercise on M1 plasticity in endurance-trained (cyclists) and sedentary individuals. 14 endurance-trained cyclists (mean ± SD; 23 ± 3.8 years) and 14 sedentary individuals (22 ± 1.8 years) performed two experimental sessions. One session included an acute bout of high-intensity interval training (HIIT) exercise involving stationary cycling, while another session involved no-exercise (control). Following exercise (or control), I-wave periodicity repetitive TMS (iTMS) was used (1.5 ms interval, 180 pairs) to induce plasticity within M1. Motor evoked potentials (MEP) induced by single and paired-pulse TMS over M1 were recorded from a hand muscle at baseline, after HIIT (or control) exercise, and after iTMS. Corticospinal and intracortical excitability was not influenced by HIIT exercise in either group (all P > 0.05). There was an increase in MEP amplitude after iTMS, and this was greater after HIIT exercise (compared with control) for all subjects (P < 0.001). However, the magnitude of this response was larger in endurance cyclists compared with the sedentary group (P < 0.05). These findings indicate that M1 plasticity induced by iTMS was greater in endurance-trained cyclists following HIIT. Prior history of exercise training is, therefore, an important consideration for understanding factors that contribute to exercise-induced plasticity.Item Metadata only Intimate partner violence during infancy and cognitive outcomes in middle childhood: Results from an Australian community-based mother and child cohort study(Wiley, 2022) Savopoulos, P.; Brown, S.; Anderson, P.J.; Gartland, D.; Bryant, C.; Giallo, R.The cognitive functioning of children who experience intimate partner violence (IPV) has received less attention than their emotional-behavioral outcomes. Drawing upon data from 615 (48.4% female) 10-year-old Australian-born children and their mothers (9.6% of mothers born in non-English speaking countries) participating in a community-based longitudinal study between 2004 and 2016, this study examined the associations between IPV in infancy and cognition in middle childhood (at age 10). Results showed that IPV in the first 12 months of life was associated with lower general cognitive ability and poorer executive attention but not working memory skills. IPV in middle childhood (in the 10th year postpartum) was not associated with cognition. This study provides evidence for the long-term impact of early life exposure to IPV on children's cognition, and points to the importance of early intervention to optimize development.Item Open Access Autofluorescent imprint of chronic constriction nerve injury identified by deep learning(Elsevier, 2021) Gosnell, M.E.; Staikopoulos, V.; Anwer, A.G.; Mahbub, S.B.; Hutchinson, M.R.; Mustafa, S.; Goldys, E.M.Our understanding of chronic pain and the underlying molecular mechanisms remains limited due to a lack of tools to identify the complex phenomena responsible for exaggerated pain behaviours. Furthermore, currently there is no objective measure of pain with current assessment relying on patient self-scoring. Here, we applied a fully biologically unsupervised technique of hyperspectral autofluorescence imaging to identify a complex signature associated with chronic constriction nerve injury known to cause allodynia. The analysis was carried out using deep learning/artificial intelligence methods. The central element was a deep learning autoencoder we developed to condense the hyperspectral channel images into a four- colour image, such that spinal cord tissue based on nerve injury status could be differentiated from control tissue. This study provides the first validation of hyperspectral imaging as a tool to differentiate tissues from nerve injured vs non-injured mice. The auto-fluorescent signals associated with nerve injury were not diffuse throughout the tissue but formed specific microscopic size regions. Furthermore, we identified a unique fluorescent signal that could differentiate spinal cord tissue isolated from nerve injured male and female animals. The identification of a specific global autofluorescence fingerprint associated with nerve injury and resultant neuropathic pain opens up the exciting opportunity to develop a diagnostic tool for identifying novel contributors to pain in individuals.Item Metadata only Motor cortex plasticity and visuomotor skill learning in upper and lower limbs of endurance-trained cyclists(Springer-Verlag, 2022) Hand, B.J.; Opie, G.M.; Sidhu, S.K.; Semmler, J.G.Purpose: Studies with transcranial magnetic stimulation (TMS) show that both acute and long-term exercise can influence TMS-induced plasticity within primary motor cortex (M1). However, it remains unclear how regular exercise influences skill training-induced M1 plasticity and motor skill acquisition. This study aimed to investigate whether skill training-induced plasticity and motor skill learning is modified in endurance-trained cyclists. Methods: In 16 endurance-trained cyclists (24.4 yrs; 4 female) and 17 sedentary individuals (23.9 yrs; 4 female), TMS was applied in 2 separate sessions: one targeting a hand muscle not directly involved in habitual exercise and one targeting a leg muscle that was regularly trained. Single- and paired-pulse TMS was used to assess M1 and intracortical excitability in both groups before and after learning a sequential visuomotor isometric task performed with the upper (pinch task) and lower (ankle dorsiflexion) limb. Results: Endurance-trained cyclists displayed greater movement times (slower movement) compared with the sedentary group for both upper and lower limbs (all P < 0.05), but there was no difference in visuomotor skill acquisition between groups (P > 0.05). Furthermore, endurance-trained cyclists demonstrated a greater increase in M1 excitability and reduced modulation of intracortical facilitation in resting muscles of upper and lower limbs after visuomotor skill learning (all P < 0.005). Conclusion: Under the present experimental conditions, these results indicate that a history of regular cycling exercise heightens skill training-induced M1 plasticity in upper and lower limb muscles, but it does not facilitate visuomotor skill acquisition.Item Metadata only Neuroimmunological complications arising from chemotherapy-induced gut toxicity and opioid exposure in female dark agouti rats(Wiley, 2022) Bajic, J.; Howarth, G.; Mashtoub, S.; Whittaker, A.; Bobrovskaya, L.; Hutchinson, M.R.Cancer patients may experience symptom clusters, including chemotherapy-induced (CI) gut toxicity (CIGT) and cognitive impairment. Analgesic selection for pain associated with CIGT is difficult as opioids induce glial reactivity and unwanted side effects. This study quantified central glial reactivity and proinflammatory effects in rats with CIGT using three mechanistically different analgesics. Regional adaptations were indicative of immune-to-brain signaling routes. Utilizing a 5-fluorouracil-induced GT (5IGT) rat model and analgesic intervention (carprofen (CAR), buprenorphine (BUP), and tramadol (TRAM)), spinal and brain neuroimmune modulation was examined via microglial, astrocyte, and proinflammatory (cluster of differentiation molecule 11b; CD11b, glial fibrillary associated protein; GFAP, and interleukin-1 beta; IL1β) reactivity marker expression changes by western blot analysis. 5IGT significantly increased thoracic GFAP (p < 0.05) and IL-1β (p < 0.0001) expression, CAR and BUP ameliorated these effects. BUP and TRAM with 5-FU synergistically increased hippocampal GFAP expression. CAR administered with 5IGT significantly elevated hippocampal and thoracic CD11b expression levels (p < 0.05). The neuroimmune responses observed in this study suggest activation of peripheral-to-central immune signaling pathways. We speculate that the opioid-induced hippocampal changes inferred a humorally mediated mechanism, whereas thoracic neuroimmune modifications indicated activation of an indirect neural route. Although TRAM ameliorated 5IGT-intestinal inflammation, this opioid presents complications relating to bodyweight and regional glial dysregulation (neuroinflammation) and may not be optimal in the management of pain associated with 5IGT. The chemotherapy-induced gut-derived neuroimmune consequences observed suggest a potential mechanistic contribution to central components of the cancer symptom cluster experience, while the opioid-related glial changes have implications for optimal pain management in this setting warranting further investigation.Item Metadata only Morphology of the nutrient artery and its foramen in relation to femoral bone perfusion rates of laying and non-laying hens(Wiley, 2021) Hu, Q.; Nelson, T.J.; Seymour, R.S.If arteries penetrate bones through foramina, regional artery blood flow rates can be estimated from the foramen sizes. Femoral bone blood flow rates estimated from nutrient foramen sizes were previously not absolute, but only a relative blood flow index (Qi), because the size relationship between the foramen and the occupying artery was unknown. The current study used vascular contrast and micro-computerized tomographic scanning to investigate femoral nutrient foramen and nutrient artery sizes in three groups of sub-adult chickens (non-laying hens, laying hens, and roosters) of similar ages. The results indicate that the cross-sectional area of the nutrient artery lumen occupies approximately 20.2 ± 4.1% of the foramen for femora with only one foramen. Artery lumen size is significantly correlated with foramen size. Vascular contrast imaging is capable of estimating blood flow rates through nutrient arteries, as blood flow rates estimated from artery lumen casts are similar to blood flow rates measured by infusion of fluorescent-labeled microspheres. Laying hens tend to have higher nutrient artery perfusion rates than non-laying hens, probably due to extra oxygen and calcium requirements for eggshell production, although the calculated blood flow difference was not statistically significant. Histological embedding and sectioning along with vascular contrast imaging reveal variable nutrient foramen morphology and nutrient artery location among femora with more than one nutrient foramen.Item Open Access Regional femoral bone blood flow rates in laying and non-laying chickens estimated with fluorescent microspheres(Company of Biologists, 2021) Hu, Q.; Nelson, T.J.; Seymour, R.S.The metabolic rate of vertebrate bone tissue is related to bone growth, repair and homeostasis, which are all dependent on life stage. Bone metabolic rate is difficult to measure directly, but absolute blood flow rate (Q̇) should reflect local tissue oxygen requirements. A recent 'foramen technique' has derived an index of blood flow rate (Qi) by measuring nutrient foramen sizes of long bones. Qi is assumed to be proportional to Q̇, however, the assumption has never been tested. This study used fluorescent microsphere infusion to measure femoral bone Q̇ in anaesthetised non-laying hens, laying hens and roosters. Mean cardiac output was 338±38 ml min-1 kg-1, and the two femora received 0.63±0.10 % of this. Laying hens had higher wet bone mass-specific Q̇ to femora (0.23±0.09 ml min-1 g-1) than the non-laying hens (0.12±0.06 ml min-1 g-1) and roosters (0.14±0.04 ml min-1 g-1), presumably associated with higher bone calcium mobilization during eggshell production. Estimated metabolic rate of femoral bone was 0.019 ml O2 min-1 g-1. Femoral Q̇ increased significantly with body mass, but was not correlated with nutrient foramen radius (r), probably due to a narrow range in foramen radius. Over all 18 chickens, femoral shaft Q̇/r was 1.07±0.30 ml min-1 mm-1. Mean Qi in chickens was significantly higher than predicted by an allometric relationship for adult cursorial bird species, possibly because the birds were still growing.Item Open Access Repetitive transcranial magnetic stimulation (rTMS) in autism spectrum disorder: protocol for a multicentre randomised controlled clinical trial(BMJ, 2021) Enticott, P.G.; Barlow, K.; Guastella, A.J.; Licari, M.K.; Rogasch, N.C.; Middeldorp, C.M.; Clark, S.R.; Vallence, A.-M.; Boulton, K.A.; Hickie, I.B.; Whitehouse, A.J.O.; Galletly, C.; Alvares, G.A.; Fujiyama, H.; Heussler, H.; Craig, J.M.; Kirkovski, M.; Mills, N.T.; Rinehart, N.J.; Donaldson, P.H.; et al.Introduction: There are no well-established biomedical treatments for the core symptoms of autism spectrum disorder (ASD). A small number of studies suggest that repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, may improve clinical and cognitive outcomes in ASD. We describe here the protocol for a funded multicentre randomised controlled clinical trial to investigate whether a course of rTMS to the right temporoparietal junction (rTPJ), which has demonstrated abnormal brain activation in ASD, can improve social communication in adolescents and young adults with ASD. Methods and analysis: This study will evaluate the safety and efficacy of a 4-week course of intermittent theta burst stimulation (iTBS, a variant of rTMS) in ASD. Participants meeting criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ASD (n=150, aged 14–40 years) will receive 20 sessions of either active iTBS (600 pulses) or sham iTBS (in which a sham coil mimics the sensation of iTBS, but no active stimulation is delivered) to the rTPJ. Participants will undergo a range of clinical, cognitive, epi/genetic, and neurophysiological assessments before and at multiple time points up to 6 months after iTBS. Safety will be assessed via a structured questionnaire and adverse event reporting. The study will be conducted from November 2020 to October 2024. Ethics and dissemination: The study was approved by the Human Research Ethics Committee of Monash Health (Melbourne, Australia) under Australia’s National Mutual Acceptance scheme. The trial will be conducted according to Good Clinical Practice, and findings will be written up for scholarly publication. Trial registration number:L Australian New Zealand Clinical Trials Registry (ACTRN12620000890932).