Tumor progression locus 2 (Tpl2) deficiency does not protect against obesity-induced metabolic disease

Obesity is associated with a state of chronic low grade inflammation that plays an important role in the development of insulin resistance. Tumor progression locus 2 (Tpl2) is a serine/threonine mitogen activated protein kinase kinase kinase (MAP3K) involved in regulating responses to specific inflammatory stimuli. Here we have used mice lacking Tpl2 to examine its role in obesity-associated insulin resistance. Wild type (wt) and tpl22/2 mice accumulated comparable amounts of fat and lean mass when fed either a standard chow diet or two different high fat (HF) diets containing either 42% or 59% of energy content derived from fat. No differences in glucose tolerance were observed between wt and tpl22/2 mice on any of these diets. Insulin tolerance was similar on both standard chow and 42% HF diets, but was slightly impaired in tpl22/2 mice fed the 59% HFD. While gene expression markers of macrophage recruitment and inflammation were increased in the white adipose tissue of HF fed mice compared with standard chow fed mice, no differences were observed between wt and tpl2 mice. Finally, a HF diet did not increase Tpl2 expression nor did it activate Extracellular Signal-Regulated Kinase 1/2 (ERK1/2), the MAPK downstream of Tpl2. These findings argue that Tpl2 does not play a non-redundant role in obesity associated metabolic dysfunction.

Prospective progression from high-prevalence disorders to bipolar disorder: exploring characteristics of pre-illness stages

BACKGROUND: Identification of risk factors within precursor syndromes, such as depression, anxiety or substance use disorders (SUD), might help to pinpoint high-risk stages where preventive interventions for Bipolar Disorder (BD) could be evaluated.

METHODS: We examined baseline demographic, clinical, quality of life, and temperament measures along with risk clusters among 52 young people seeking help for depression, anxiety or SUDs without psychosis or BD. The risk clusters included Bipolar At-Risk (BAR) and the Bipolarity Index as measures of bipolarity and the Ultra-High Risk assessment for psychosis. The participants were followed up for 12 months to identify conversion to BD. Those who converted and did not convert to BD were compared using Chi-Square and Mann Whitney U tests.

RESULTS: The sample was predominantly female (85%) and a majority had prior treatment (64%). Four participants converted to BD over the 1-year follow up period. Having an alcohol use disorder at baseline (75% vs 8%, χ(2)=14.1, p<0.001) or a family history of SUD (67% vs 12.5%, χ(2)=6.0, p=0.01) were associated with development of BD. The sub-threshold mania subgroup of BAR criteria was also associated with 12-month BD outcomes. The severity of depressive symptoms and cannabis use had high effects sizes of association with BD outcomes, without statistical significance.

CONCLUSIONS AND LIMITATIONS: The small number of conversions limited the power of the study to identify associations with risk factors that have previously been reported to predict BD. However, subthreshold affective symptoms and SUDs might predict the onset of BD among help-seeking young people with high-prevalence disorders.

Discrimination, Peformance and Career Progression in Australian Public Sector Labor Markets

While promotion is an important mechanism for allocating labor within organizations, relatively little is known about the determinants of promotion in the highly diverse and traditionally heavily regulated Australian labor markets. This study uses unique data from the Victorian Public Sector Census 2004 to identify the extent and nature of bias in the promotion process. Specifically, we use the promotion histories of 16,675 public sector employees to investigate the existence of discrimination in promotion on the basis of gender, disability and cultural diversity. We find that some differences exist in the rate of promotion on the basis of gender, and to a lesser extent, of birthplace, but, importantly, most of these are due to differences in endowments. There are effectively no differences in promotion on the basis of disability. We find that the main driver of promotion in Victorian public sector labor markets is worker effort and performance. Compared to labor markets elsewhere, the Australian public sector is relatively free of discrimination in promotions.

Dysglycaemia and other predictors for progression or regression from impaired fasting glucose to diabetes or normoglycaemia

Aims. Diabetes mellitus is a growing health problem worldwide. This study aimed to describe dysglycaemia and determine the impact of body composition and clinical and lifestyle factors on the risk of progression or regression from impaired fasting glucose (IFG) to diabetes or normoglycaemia in Australian women. Methods. This study included 1167 women, aged 20-94 years, enrolled in the Geelong Osteoporosis Study. Multivariable logistic regression was used to identify predictors for progression to diabetes or regression to normoglycaemia (from IFG), over 10 years of follow-up. Results. At baseline the proportion of women with IFG was 33.8% and 6.5% had diabetes. Those with fasting dysglycaemia had higher obesity-related factors, lower serum HDL cholesterol, and lower physical activity. Over a decade, the incidence of progression from IFG to diabetes was 18.1 per 1,000 person-years (95% CI, 10.7-28.2). Fasting plasma glucose and serum triglycerides were important factors in both progression to diabetes and regression to normoglycaemia. Conclusions. Our results show a transitional process; those with IFG had risk factors intermediate to normoglycaemics and those with diabetes. This investigation may help target interventions to those with IFG at high risk of progression to diabetes and thereby prevent cases of diabetes.

Occupational therapists' experiences of career progression following promotion

BACKGROUND/AIM: The recruitment and retention of a skilled occupational therapy workforce is highlighted as a key issue for the profession, and yet there have been relatively few studies into the career progression of occupational therapists. METHODS: A qualitative, naturalistic approach was adopted to answer the research question, using semi-structured interviews to gather data. Eleven purposefully selected participants at an Australian health service were interviewed as part of this study. Categories representing the most common themes and topics supplied by participants within their individual interviews were identified and consolidated by the research team. The trustworthiness of this study was supported by strategies to maximise its credibility, dependability and confirmability. RESULTS: Four main themes were elicited from the data - (i) Readiness for progression, (ii) Tools and processes, (iii) Expectations and (iv) What I wish I had known first. Within these themes, related findings were also identified by both Grade 2 and Grade 3 staff. CONCLUSIONS: This study indicates that the readiness of occupational therapists to climb the career ladder is influenced by the tools and processes they can utilise, and the expectations they have around the realities of their new position. With hindsight, participants highlighted some things they wish they had known at the time of transition, which appeared to have been implicit. SIGNIFICANCE OF STUDY: This study is the first to address the common issues for occupational therapy staff around progression between grade levels. It therefore provides a basis for further research in other practice settings and for the development of supports for therapists climbing the career ladder.

Coassembled nanostructured bioscaffold reduces the expression of proinflammatory cytokines to induce apoptosis in epithelial cancer cells

The local inflammatory environment of the cell promotes the growth of epithelial cancers. Therefore, controlling inflammation locally using a material in a sustained, non-steroidal fashion can effectively kill malignant cells without significant damage to surrounding healthy cells. A promising class of materials for such applications are the nanostructured scaffolds formed by epitope containing minimalist self-assembled peptides (SAPs), as they are bioactive on a cellular length scale, whilst presenting as an easily handled hydrogel. Here, we show that the assembly process distributes an anti-inflammatory polysaccharide, fuccoidan, localised to the nanofibers to function as an anti-inflammatory biomaterial for cancer therapy. We show that it supports healthy cells, whilst inducing apoptosis in cancerous endothelial cells, as demonstrated by the downregulation of the proinflammatory gene and protein expression pathways associated with epithelial cancer progression. Our findings highlight an innovative material approach with potential applications as local epithelial cancer immunotherapy and drug delivery vehicles.