https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:18353 Wed 24 Jun 2015 13:30:14 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49965 Wed 21 Jun 2023 11:57:33 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41102 Tue 26 Jul 2022 14:20:11 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42296  20% as key exposure variables. New significant AKI was defined as an AKI-stage increase of two or more (Kidney Disease: Improving Global Outcome creatinine-based criteria). Measurements and Main Results: The median MPP deficit was 19% (interquartile range, 13–25), and 54% (interquartile range, 19–82) of time points were spent with an MPP deficit > 20%. Seventy-three (24%) patients developed new significant AKI; 86 (29%) patients developed MAKE. For every percentage increase in the time-weighted average MPP deficit, multivariable-adjusted odds of developing new significant AKI and MAKE increased by 5.6% (95% confidence interval, 2.2–9.1; P = 0.001) and 5.9% (95% confidence interval, 2.2–9.8; P = 0.002), respectively. Likewise, for every one-unit increase in the percentage of time points with an MPP deficit > 20%, multivariable-adjusted odds of developing new significant AKI and MAKE increased by 1.2% (0.3–2.2; P = 0.008) and 1.4% (0.4–2.4; P = 0.004), respectively. Conclusions: Vasopressor-treated patients with shock are often exposed to a significant degree and duration of relative hypotension, which is associated with new-onset, adverse kidney-related outcomes.Study registered with Australian New Zealand Clinical Trial Registry (ACTRN 12613001368729).]]> Tue 21 Mar 2023 18:30:16 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54312 Tue 20 Feb 2024 14:27:17 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41876 Tue 16 Aug 2022 14:17:45 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:25793 Thu 27 Jan 2022 15:58:17 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33159 in vivo murine model of COPD, and primary human bronchial epithelial cells. Localization of miR-218-5p was assessed by in situ hybridization. In vitro and in vivo perturbation of miR-218-5p combined with RNA sequencing and gene set enrichment analysis was used to elucidate its functional role in COPD pathogenesis. Measurements and Main Results: Several miRNAs were differentially expressed among the different patient groups. Interestingly, miR-218-5p was significantly down-regulated in smokers without airflow limitation and in patients with COPD compared with never-smokers. Decreased pulmonary expression of miR-218-5p was validated in an independent validation cohort, in cigarette smoke-exposed mice, and in human bronchial epithelial cells. Importantly, expression of miR-218-5p strongly correlated with airway obstruction. Furthermore, cellular localization of miR-218-5p in human and murine lung revealed highest expression of miR-218-5p in the bronchial airway epithelium. Perturbation experiments with a miR-218-5p mimic or inhibitor demonstrated a protective role of miR-218-5p in cigarette smoke-induced inflammation and COPD. Conclusions: We highlight a role for miR-218-5p in the pathogenesis of COPD.]]> Thu 03 Feb 2022 12:18:37 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19253 Sun 02 Aug 2015 18:00:16 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:7529 Sat 24 Mar 2018 08:38:29 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:7897 Sat 24 Mar 2018 08:35:09 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:7187 Sat 24 Mar 2018 08:34:12 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:7255 Sat 24 Mar 2018 08:33:49 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:1310 0.05). Corticotropin-releasing hormone (CRH), a potent vasodilator that acts via the nitric oxide pathway, caused a dose-dependent vasodilatory response in all placentae in vitro. However, CRH-induced dilation was significantly reduced in moderate and severe asthmatics (ANOVA, p < 0.05). Vasoconstrictor responses to potassium chloride and prostaglandin F2alpha were reduced in placentae from moderate and severe asthmatic women (ANOVA, p < 0.05). These studies demonstrate significant differences in placental vascular function in pregnancies complicated by asthma, which may relate directly to the asthma or be a consequence of the associated glucocorticoid treatment. These changes in vascular function in asthmatic pregnancies may contribute to the low-birthweight outcome observed in this condition.]]> Sat 24 Mar 2018 08:32:42 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:1274 2.5%) was 45% in the wheeze group, which was significantly higher than the control group (9.35%, p = 0.04). Eosinophilic bronchitis was present in two children with cough (20%) and two with chest colds (15%, p > 0.05 versus control). In these groups, eosinophilic bronchitis was not associated with airway hyperresponsiveness (AHR) to hypertonic saline (p > 0.05). Children with cough and chest colds reported greater exposure to environmental tobacco smoke. In conclusion, this community-based survey of children with chronic respiratory symptoms has shown that wheeze is a good discriminator for the presence of eosinophilic bronchitis, and that persistent cough and recurrent chest colds without wheeze should not be considered a variant of asthma. Eosinophilic bronchitis did occur in a significant minority of these "variant asthma" syndromes.]]> Sat 24 Mar 2018 08:32:31 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:1792 Sat 24 Mar 2018 08:27:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:15980 Sat 24 Mar 2018 08:23:40 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13298 Sat 24 Mar 2018 08:18:04 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:12974 Sat 24 Mar 2018 08:16:09 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11251 Sat 24 Mar 2018 08:10:53 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:16925 Sat 24 Mar 2018 08:00:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19226 Sat 24 Mar 2018 07:54:52 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:5522 Sat 24 Mar 2018 07:46:42 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27614 Sat 24 Mar 2018 07:39:40 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29228 2) of 88-92% (n = 52) or a liberal oxygenation strategy with target SpO₂ of greater than or equal to 96% (n = 51). MeasurementsandMainResults:Themean area under the curve and 95% confidence interval (CI) for SpO₂ (93.4% [92.9-93.9%] vs. 97% [96.5-97.5%]), SaO₂ (93.5% [93.1-94%] vs. 96.8% [96.3-97.3%]), PaO₂ (70 [68-73] mm Hg vs. 92 [89-96] mm Hg), and FIO₂ (0.26 [0.25-0.28] vs. 0.36 [0.34-0.39) in the conservative versus liberal oxygenation arm were significantly different (P < 0.0001 for all). There were no significant between-group differences in any measures of new organ dysfunction, or ICU or 90-day mortality. The percentage time spent with SpO₂ less than 88% in conservative versus liberal arm was 1% versus 0.3% (P = 0.03), and percentage time spent with SpO₂ greater than 98% in conservative versus liberal arm was 4% versus 22% (P < 0.001). The adjusted hazard ratio for 90-day mortality in the conservative arm was 0.77 (95% CI, 0.40-1.50; P = 0.44) overall and 0.49 (95% CI, 0.20-1.17; P = 0.10) in the prespecified subgroup of patients with a baseline PaO₂/FIO₂ less than 300. Conclusions: Our study supports the feasibility of a conservative oxygenation strategy in patients receiving IMV. Larger randomized controlled trials of this intervention appear justified.]]> Sat 24 Mar 2018 07:36:48 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:4857 Sat 24 Mar 2018 07:18:49 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:24441 Sat 24 Mar 2018 07:17:27 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22085 Sat 24 Mar 2018 07:15:16 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22754 BR), and intrapericardial (IPC) catheters were placed in pericardial sac for drug infusion. Arterial and central venous catheters were placed in omocervical vessels for measurement of blood pressures. IPC infusion of 2% procaine (16 mgkg^-1) significantly (all P<0.05) raised resting heart rate (HR, to 210% of control), aortic pressure (P_a, 115%), Q_BR (146%) and bronchial flow conductance (C_BR, 125%). In 6 dogs, IPC nicotine (0.5-16μgkg^-1) produced transient bradycardia and hypotension, characteristic of vagal afferent stimulation in anesthetised dogs, before significantly (all P<0.05) raising HR (114%), P_a (121%), Q_BR (142%) and C_BR(126%) 80 seconds after injection. IPC veratridine (2-20μg) significantly (all P<0.05) raised HR (134%), P_a(108%), Q_BR (164%) and C_BR (155%) at 65 seconds. Responses to both stimuli were blocked by prior IPC application of procaine. The results suggest that cardiac sympathetic afferents tonically constrict the bronchial circulation at rest in the awake dog. Further, the chemical stimuli used cause non-specific activation of both sympathetic and vagal afferents to evoke a mixed cardiovascular response where a dilator mechanism prevails in the bronchial circulation, and a sympathoexcitatory effect in the systemic circulation. The findings are relevant to pulmonary congestion in heart failure syndromes.]]> Sat 24 Mar 2018 07:14:16 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22114 Chlamydia-induced lung disease was observed 10–15 days after infection, as evidenced by increased bacterial numbers and histopathology in the lung and a reduction in weight gain. After 6 weeks, infection and histopathology had resolved and the rate of weight gain had recovered. Neonatal but not adult infection resulted in significant decreases in interleukin-5 production from helper T cells and by the numbers of eosinophils recruited to the lung in response to ovalbumin exposure. Remarkably, the effects of early-life infection were associated with the generation of both type 1 and 2 ovalbumin-specific helper T-cell cytokine and antibody responses. Furthermore, although neonatal infection significantly attenuated eosinophilia, the generation of the mixed T-cell response exacerbated other hallmark features of asthma: mucus hypersecretion and airway hyperresponsiveness. Moreover, infection prolonged the expression of AAD and these effects were restricted to early-life infection. Conclusions: Early-life chlamydial infection induces a mixed type 1 and 2 T-cell response to antigen, which differentially affects the development of key features of AAD in the adult.]]> Sat 24 Mar 2018 07:13:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51768 Mon 18 Sep 2023 14:30:32 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51767 Mon 18 Sep 2023 14:30:18 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33076 Chlamydia and Haemophilus respiratory infection-mediated, ovalbumin-induced severe, steroid-resistant allergic airway disease. These models share the hallmark features of human disease, including elevated airway neutrophils, and NLRP3 inflammasome and IL-1ß responses. The roles and potential for targeting of NLRP3 inflammasome, caspase-1, and IL-1ß responses in experimental severe, steroid-resistant asthma were examined using a highly selective NLRP3 inhibitor, MCC950; the specific caspase-1 inhibitor Ac-YVAD-cho; and neutralizing anti-IL-1ß antibody. Roles for IL-1ß-induced neutrophilic inflammation were examined using IL-1ß and anti-Ly6G. Measurements and Main Results: Chlamydia and Haemophilus infections increase NLRP3, caspase-1, IL-1ß responses that drive steroid-resistant neutrophilic inflammation and airway hyperresponsiveness. Neutrophilic airway inflammation, disease severity, and steroid resistance in human asthma correlate with NLRP3 and IL-1ß expression. Treatment with anti-IL-1ß, Ac- YVAD-cho, and MCC950 suppressed IL-1ß responses and the important steroid-resistant features of disease in mice, whereas IL-1ß administration recapitulated these features. Neutrophil depletion suppressed IL-1ß-induced steroid-resistant airway hyperresponsiveness. Conclusions: NLRP3 inflammasome responses drive experimental severe, steroid-resistant asthma and are potential therapeutic targets in this disease.]]> Fri 24 Aug 2018 14:40:56 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45534 Fri 04 Nov 2022 14:45:29 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:24497 Ex vivo knockdown of these microRNAs restored TLR7 expression with concomitant augmentation of virus-induced IFN production. Conclusions: In severe asthma, TLR7 deficiency drives impaired innate immune responses to virus by AMs. Blocking a group of microRNAs that are up-regulated in these cells can restore antiviral innate responses, providing a novel approach for therapy in asthma.]]> Fri 01 Apr 2022 09:26:07 AEDT ]]>