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Now showing 1 - 8 of 8
  • (2012) Sunderland, Matthew; Wong, Nora; Hilvert-Bruce, Zita; Andrews, Gavin
    Journal Article
    Internet based cognitive behavioural therapy (CBT) is efficacious for the treatment of anxiety and depression. The current study aimed to examine the effectiveness of internet based CBT prescribed by primary care clinicians for the treatment of depression and generalised anxiety disorder. Psychological distress data from 302 patients who completed an online CBT course for depression and 361 patients who completed an online CBT course for generalised anxiety disorder were subjected to growth mixture analysis. For both disorders psychological distress decreased across each lesson in a quadratic trend. Two classes of individuals were identified with different trajectories of change: a large group of individuals who responded well to the courses and a smaller group of individuals with a lower response. Both groups were similar with respect to sociodemographic characteristics however the low responders tended to have higher levels of symptom severity and psychological distress at baseline in comparison to the responders. For the majority of patients (75-80%) the internet CBT courses for depression and generalised anxiety disorder were effective. Further research is required to identify and effectively treat the smaller proportion of patients who did not improve during internet CBT.

  • (2013) Williams, Alishia; Lau, Gloria; Grisham, Jessica
    Journal Article
    Background and Objectives: Thought-action fusion (TAF), or maladaptive cognitions regarding the relationship between mental events and behaviours, has been implicated in the development and maintenance of obsessive-compulsive disorder (OCD). As some religions promote TAF-like appraisals, it has been proposed that religiosity may play a role in the transformation of normally occurring intrusive thoughts into clinically distressing obsessions. No research, however, has experimentally investigated the mediating role of TAF on the relationship between religiosity and OC symptoms. Methods: 85 Christian, Jewish, and Atheist/Agnostic participants were exposed to an experimental thought-induction protocol and reported on their associated levels of distress, guilt, feelings of responsibility, and urge to suppress target intrusions experienced during a 5-minute monitoring period. Participants also completed measures of obsessive-compulsive symptomatology, TAF beliefs, and general psychopathology. Results: Using PROCESS and bootstrapping analyses, a test of the conditional indirect effects of religiosity on obsessive-compulsive symptoms revealed that Christianity moderated the effects of religiosity on moral TAF beliefs, which in turn mediated the relationship between religiosity and obsessive-compulsive symptoms. Furthermore, in the Christian group, moral TAF beliefs mediated the relationship between religiosity and ratings of guilt and responsibility following the experimental protocol. Limitations: The use of university students with moderate levels of religiosity. Conclusions: Collectively the results suggest that obsessional thinking is not attributable to religion per se, but that teachings underlying certain religious doctrines may fuel TAF beliefs that are implicated in the maintenance of OCD.

  • (2012) Funnell, Alister; Norton, Laura; Mak, Ka Sin; Burdach, John; Artuz, Crisbel; Twine, Natalie; Wilkins, Marc; Hung, TT; Perdomo, Jose; Power, Carl; Koh, P; Bell Anderson, Kim; Orkin, S; Fraser, Stuart; Perkins, Andrew; Pearson, Richard; Crossley, Merlin
    Journal Article
    The CACCC-box binding protein erythroid Krüppel-like factor (EKLF/KLF1) is a master regulator that directs the expression of many important erythroid genes. We have previously shown that EKLF drives transcription of the gene for a second KLF, basic Krüppel-like factor, or KLF3. We have now tested the in vivo role of KLF3 in erythroid cells by examining Klf3 knockout mice. KLF3-deficient adults exhibit a mild compensated anemia, including enlarged spleens, increased red pulp, and a higher percentage of erythroid progenitors, together with elevated reticulocytes and abnormal erythrocytes in the peripheral blood. Impaired erythroid maturation is also observed in the fetal liver. We have found that KLF3 levels rise as erythroid cells mature to become TER119(+). Consistent with this, microarray analysis of both TER119(-) and TER119(+) erythroid populations revealed that KLF3 is most critical at the later stages of erythroid maturation and is indeed primarily a transcriptional repressor. Notably, many of the genes repressed by KLF3 are also known to be activated by EKLF. However, the majority of these are not currently recognized as erythroid-cell-specific genes. These results reveal the molecular and physiological function of KLF3, defining it as a feedback repressor that counters the activity of EKLF at selected target genes to achieve normal erythropoiesis.

  • (2014) Anderson, Amy; Hure, A; Forder, P; Powers, J; Kay-Lambkin, Frances; Loxton, D
    Journal Article

  • (2012) Anderson, Amy; Hure, Alexis J; Powers, Jennifer; Kay-Lambkin, Frances; Loxton, Deborah J
    Journal Article

  • (2008) Braidy, Nady; Guillemin, Gilles; Grant, Ross
    Journal Article
    Oxidative imbalance is a prominent feature in Alzheimer's disease and ageing. Increased levels of reactive oxygen species (ROS) can result in disordered cellular metabolism due to lipid peroxidation, protein-cross linking, DNA damage and the depletion of nicotinamide adenine dinucleotide (NAD+). NAD+ is a ubiquitous pyridine nucleotide that plays an essential role in important biological reactions, from ATP production and secondary messenger signalling, to transcriptional regulation and DNA repair. Chronic oxidative stress may be associated with NAD+ depletion and a subsequent decrease in metabolic regulation and cell viability. Hence, therapies targeted toward maintaining intracellular NAD+ pools may prove efficacious in the protection of age-dependent cellular damage, in general, and neurodegeneration in chronic central nervous system inflammatory diseases such as Alzheimer's disease, in particular.

  • (2009) Shen, Bojiang; Bhargav, Divya; Wei, Ai-Qun; Williams, Lisa; Diwan, Ashish
    Journal Article
    Bone morphogenetic protein-13 (BMP-13) plays an important role in skeletal development. In the light of a recent report that mutations in the BMP-13 gene are associated with spine vertebral fusion in Klippel-Feil syndrome, we hypothesized that BMP-13 signaling is crucial for regulating embryonic endochondral ossification. In this study, we found that BMP-13 inhibited the osteogenic differentiation of human bone marrow multipotent mesenchymal stromal cells (BM MSCs) in vitro. The endogenous BMP-13 gene expression in MSCs was examined under expansion conditions. The MSCs were then induced to differentiate into osteoblasts in osteo-inductive medium containing exogenous BMP-13. Gene expression was analysed by real-time PCR. Alkaline phosphatase (ALP) expression and activity, proteoglycan (PG) synthesis and matrix mineralization were assessed by cytological staining or ALP assay. Results showed that endogenous BMP-13 mRNA expression was higher than BMP-2 or -7 during MSC growth. BMP-13 supplementation strongly inhibited matrix mineralization and ALP activity of osteogenic differentiated MSCs, yet increased PG synthesis under the same conditions. In conclusion, BMP-13 inhibited osteogenic differentiation of MSCs, implying that functional mutations or deficiency of BMP-13 may allow excess bone formation. Our finding provides an insight into the molecular mechanisms and the therapeutic potential of BMP-13 in restricting pathological bone formation.

  • (2001) O'Sullivan, Anthony; Martin, Allison; Brown, Mark
    Journal Article
    There is a sexual dimorphism in body fat in humans. Adipose tissue increases with puberty and early pregnancy in women, suggesting gonadal steroids can influence body fat. Previously, we have observed that oral estrogen, compared with transdermal estrogen, reduced postprandial lipid oxidation and increased body fat, possibly due to suppressed hepatic lipid oxidation. If estrogen effects lipid oxidation, we predicted that subjects with significantly different endogenous estrogen production would oxidize lipids at different rates. The aim of this study was to compare energy metabolism in 12 pregnant (19 wk gestation, 29 ± 1 yr, 1.66 ± 0.02 m, 73.5 ± 2.4 kg), 11 nonpregnant premenopausal (29 ± 2 yr, 1.68 ± 0.02 m, 63.1 ± 1.8 kg), and 28 postmenopausal (58 ± 1 yr, 1.62 ± 0.01 m, 69.9 ± 1.0 kg) women who were not receiving estrogen, and to relate these findings to endogenous estrogen concentrations. All women underwent indirect calorimetry under identical situations in the basal and postprandial state following a standard mixed meal. Basal (5998 ± 184 vs. 5712 ± 184 vs. 5800 ± 121 kJ·24 h, respectively) and postprandial energy expenditure (7172 ± 239 vs. 6964 ± 210 vs. 6955 ± 147 kJ·24 h) was similar among groups. However, basal lipid oxidation was reduced in pregnant (45.3 ± 6.1 mg/min, P < 0.05) and nonpregnant women (44.5 ± 6.3 mg/min, P < 0.05) compared with postmenopausal women (58.4 ± 2.9 mg/min). Postprandial lipid oxidation differed among groups, being least in pregnant women (8.8 ± 6.2 mg/min) compared with nonpregnant (28.9 ± 6.4 mg/min, P < 0.04) and postmenopausal (48.1 ± 4.0 mg/min, P = 0.0001) women. There was a significant reciprocal increase in postprandial carbohydrate oxidation. Mean postprandial glucose levels were slightly but nonsignificantly higher in pregnant women. Insulin levels were significantly higher in postmenopausal compared nonpregnant, but not pregnant, women. In a multiple regression analysis, serum estradiol (log transformed) correlated negatively with postprandial lipid oxidation (r = -0.66, P = 0.0001) and positively with postprandial nonesterified free fatty acid levels, whereas no correlation was found with postprandial insulin, glucose, fat free mass, and fat mass. In summary, postprandial lipid oxidation is reduced in pregnancy compared with that in healthy nonpregnant women, who in turn have lower postprandial lipid oxidation than postmenopausal women. This implies that the premenopausal years and early pregnancy are states of efficient fat storage, possibly mediated through reduced lipid oxidation due to estrogen, therefore increasing body fat for reproduction, thus supporting the notion that fat mass can be regulated.