https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52020 Wed 27 Sep 2023 09:54:11 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22648 Wed 22 May 2019 14:50:34 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33577 in vitro and that C3a receptor signalling stimulates neurogenesis in unchallenged adult mice. To determine the role of C3a-C3a receptor signalling in ischaemia-induced neural plasticity, we subjected C3a receptor-deficient mice, GFAP-C3a transgenic mice expressing biologically active C3a in the central nervous system, and their respective wild-type controls to photothrombotic stroke. We found that C3a overexpression increased, whereas C3a receptor deficiency decreased post-stroke expression of GAP43 (P < 0.01), a marker of axonal sprouting and plasticity, in the peri-infarct cortex. To verify the translational potential of these findings, we used a pharmacological approach. Daily intranasal treatment of wild-type mice with C3a beginning 7 days after stroke induction robustly increased synaptic density (P < 0.01) and expression of GAP43 in peri-infarct cortex (P < 0.05). Importantly, the C3a treatment led to faster and more complete recovery of forepaw motor function (P < 0.05). We conclude that C3a-C3a receptor signalling stimulates post-ischaemic neural plasticity and intranasal treatment with C3a receptor agonists is an attractive approach to improve functional recovery after ischaemic brain injury.]]> Wed 17 Nov 2021 16:30:36 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54611 Wed 06 Mar 2024 10:38:32 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:39111 Tue 21 Mar 2023 17:45:24 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52120 Thu 28 Sep 2023 15:04:45 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52650 0.66). Conversely, dorsal putamen showed reduced modulation over lateral prefrontal cortex activity (Pp > 0.90). These functional deregulations emerged on top of a generally intact anatomical substrate. We provide out-of-sample replication of opposite changes in ventro-anterior and dorso-posterior frontostriatal connectivity in OCD and advance the understanding of the neural underpinnings of these functional perturbations. These findings inform the development of targeted therapies normalizing frontostriatal dynamics in OCD.]]> Thu 19 Oct 2023 15:19:31 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:8115 Sat 24 Mar 2018 08:40:00 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:8108 Sat 24 Mar 2018 08:40:00 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20806 7-fold (hazard ratio 7.34, 95%, confidence interval 5.08-10.58) and a >8-fold (hazard ratio 8.44, 95%, confidence interval 4.64-15.37) increased risk of early-onset dementia and early-onset mild cognitive impairment, respectively. In conclusion, lower cardiovascular fitness and cognitive performance in early adulthood were associated with an increased risk of early-onset dementia and mild cognitive impairment later in life, and the greatest risks were observed for individuals with a combination of low cardiovascular fitness and low cognitive performance.]]> Sat 24 Mar 2018 08:05:52 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17430 2 s was the most accurate computed tomography perfusion threshold in predicting the extent of critically hypoperfused tissue with both receiver operating curve analysis (area under curve 0.86), and the volumetric validation (mean difference between computed tomography perfusion and 24-h diffusion-weighted imaging lesions = 2 cm², 95% confidence interval 0.5–3.2 cm²). Cerebral blood flow <40% (of contralateral) within the relative delay time >2 s perfusion lesion was the most accurate computed tomography perfusion threshold at defining infarct core with both receiver operating characteristic analysis (area under curve = 0.85) and the volumetric validation. Using these thresholds, the extent of computed tomography perfusion mismatch tissue (the volume of ‘at-risk’ tissue between the critically hypoperfused and core thresholds) salvaged from infarction correlated with clinical improvement at 24 h (R² = 0.59, P = 0.04) and 90 days (R² = 0.42, P = 0.02). Patients with larger baseline computed tomography perfusion infarct core volume (>25 ml) also had poorer recovery at Day 90 (P = 0.039). Computed tomography perfusion can accurately identify critically hypoperfused tissue that progresses to infarction without early reperfusion, and the computed tomography perfusion cerebral blood flow infarct core closely predicts the final volume of infarcted tissue in patients who do reperfuse. The computed tomography perfusion infarct core and at-risk measures identified are also strong predictors of clinical outcome.]]> Sat 24 Mar 2018 08:01:40 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28805 P < 10⁻¹²). However, the female-to-male ratio in patients with relapse-onset multiple sclerosis and zero relapses in any given year was double that of the patients with primary progressive multiple sclerosis. Patient age was a more important determinant of decline in relapse incidence than disease duration (P < 10⁻¹²). Females are predisposed to higher relapse activity than males. However, this difference does not explain the markedly lower female-to-male sex ratio in primary progressive multiple sclerosis. Decline in relapse activity over time is more closely related to patient age than disease duration.]]> Sat 24 Mar 2018 07:38:27 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27383 -16). Furthermore, we identify a novel association signal of rs9807334, near the ELAC1/SMAD4 genes, for oligoclonal band status (P = 8.45 x 10^-7). The previously reported association of the immunoglobulin heavy chain locus with immunoglobulin G index reaches strong evidence for association in this data set (P = 3.79 x 10^-37). We identify two novel associations in the major histocompatibility complex region with immunoglobulin G index: the rs9271640*A-rs6457617*G haplotype (P = 1.59 x 10^-22), shared with oligoclonal band status, and an additional independent effect of rs6457617*G (P = 3.68 x 10^-6). Variants identified in this study account for up to 2-fold differences in the odds of being oligoclonal band positive and 7.75% of the variation in immunoglobulin G index. Both traits are associated with clinical features of disease such as female gender, age at onset and severity. This is the largest study population so far investigated for the genetic influence on antibody levels in the cerebrospinal fluid in multiple sclerosis, including 6950 patients. We confirm that genetic factors underlie these antibody levels and identify both the major histocompatibility complex and immunoglobulin heavy chain region as major determinants.]]> Sat 24 Mar 2018 07:34:11 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27223 M-H = 0.08). These results point to a role of the NLRP3 inflammasome and its related cytokine IL1B in the response to interferon beta in patients with relapsing-remitting multiple sclerosis.]]> Sat 24 Mar 2018 07:32:24 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22755 1.8 and volume >15 ml, core <70 ml). In a second analysis, we compared outcomes of the perfusion computed tomography-selected rtPA-treated patients to an Australian historical cohort of non-contrast computed tomography-selected rtPA-treated patients. Of 635 patients with acute ischaemic stroke eligible for rtPA by standard criteria, thrombolysis was given to 366 patients, with 269 excluded based on visual real-time perfusion computed tomography assessment. After off-line quantitative perfusion computed tomography classification: 253 treated patients and 83 untreated patients had 'target' mismatch, 56 treated and 31 untreated patients had a large ischaemic core, and 57 treated and 155 untreated patients had no target mismatch. In the primary analysis, only in the target mismatch subgroup did rtPA-treated patients have significantly better outcomes (odds ratio for 3-month, modified Rankin Scale 0-2 = 13.8, P < 0.001). With respect to the perfusion computed tomography selected rtPA-treated patients (n = 366) versus the clinical/non-contrast computed tomography selected rtPA-treated patients (n = 396), the perfusion computed tomography selected group had higher adjusted odds of excellent outcome (modified Rankin Scale 0-1 odds ratio 1.59, P = 0.009) and lower mortality (odds ratio 0.56, P = 0.021). Although based on observational data sets, our analyses provide support for the hypothesis that perfusion computed tomography improves the identification of patients likely to respond to thrombolysis, and also those in whom natural history may be difficult to modify with treatment.]]> Mon 11 Mar 2019 12:14:50 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:25306 Mon 06 Mar 2023 17:55:37 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34026 80%) for relapse incidence during the first year and for disability outcomes, moderate for relapse incidence in Years 2–4 and for the change in the cumulative disease burden, and low for conversion to secondary progressive disease and treatment discontinuation. External validation showed similar results, demonstrating high external validity for disability and relapse outcomes, moderate external validity for cumulative disease burden and low external validity for conversion to secondary progressive disease and treatment discontinuation. We conclude that demographic, clinical and paraclinical information helps predict individual response to disease-modifying therapies at the time of their commencement.]]> Fri 01 Feb 2019 10:45:46 AEDT ]]>