Mitochondrial dysfunction in schizophrenia : Pathways, mechanisms and implications.

Mitochondria play a critical role in regulating cellular functions including bioenergetics, calcium homeostasis, redox signalling, and apoptotic cell death. Mitochondria are also essential to many aspects of neurodevelopment and neuronal functions. However, mitochondrial impairment may affect bioenergetics in the developing brain and alter critical neuronal processes leading to neurodevelopmental abnormalities. Schizophrenia is a chronic and severe neuropsychiatric disorder of neurodevelopmental origin. Immuno-inflammatory pathway is one of the widely appreciated mechanisms that has consistently been implicated in the neurodevelopmental origin of schizophrenia. However, the source of inflammation and the underlying neurobiological mechanisms leading to schizophrenia are yet to be fully ascertained. Recent understanding reveals that perturbation of mitochondrial network dynamics might lead to various nervous system disorders with inflammatory pathologies. Mitochondrial deficit, altered redox balance and chronic low-grade inflammation are evident in schizophrenia. It is hypothesized that oxidative/nitrosative stress responses due to mitochondrial dysfunctions might activate immuno-inflammatory pathways and subsequently lead to neuroprogressive changes in schizophrenia. Herein, we summarise the current understanding of molecular links between mitochondrial dysfunctions and pathogenesis of schizophrenia based on evidence from genomics, proteomics and imaging studies, which together support a role for mitochondrial impairment in the pathogenetic pathways of schizophrenia.

Central pathways causing fatigue in neuro-inflammatory and autoimmune illnesses

The genesis of severe fatigue and disability in people following acute pathogen invasion involves the activation of Toll-like receptors followed by the upregulation of proinflammatory cytokines and the activation of microglia and astrocytes. Many patients suffering from neuroinflammatory and autoimmune diseases, such as multiple sclerosis, Parkinson's disease and systemic lupus erythematosus, also commonly suffer from severe disabling fatigue. Such patients also present with chronic peripheral immune activation and systemic inflammation in the guise of elevated proinflammtory cytokines, oxidative stress and activated Toll-like receptors. This is also true of many patients presenting with severe, apparently idiopathic, fatigue accompanied by profound levels of physical and cognitive disability often afforded the non-specific diagnosis of chronic fatigue syndrome.

MicroRNA pathways : an emerging role in identification of therapeutic strategies

For years researchers have exerted every effort to improve the influential roles of microRNA (miRNA) in regulating genes that direct mammalian cell development and function. In spite of numerous advancements, many facets of miRNA generation remain unresolved due to the perplexing regulatory networks. The biogenesis of miRNA, eminently endures as a mystery as no universal pathway defines or explicates the variegation in the rise of miRNAs. Early evidence in biogenesis ignited specific steps of being omitted or replaced that eventuate in the individual miRNAs of different mechanisms. Understanding the basic foundation concerning how miRNAs are generated and function will help with diagnostic tools and therapeutic strategies. This review encompasses the canonical and the non-canonical pathways involved in miRNA biogenesis, while elucidating how miRNAs regulate genes at the nuclear level and also the mechanism that lies behind circulating miRNAs.

Graphene quantum dots induce apoptosis, autophagy, and inflammatory response via p38 mitogen-activated protein kinase and nuclear factor-κB mediated signaling pathways in activated THP-1 macrophages.

The biomedical application of graphene quantum dots (GQDs) is a new emerging area. However, their safety data are still in scarcity to date. Particularly, the effect of GQDs on the immune system remains unknown. This study aimed to elucidate the interaction of GQDs with macrophages and the underlying mechanisms. Our results showed that GQDs slightly affected the cell viability and membrane integrity of macrophages, whereas GQDs significantly increased reactive oxygen species (ROS) generation and apoptotic and autophagic cell death with an increase in the expression level of Bax, Bad, caspase 3, caspase 9, beclin 1, and LC3-I/II and a decrease in that of Bcl-2. Furthermore, low concentrations of GQDs significantly increased the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-8, whereas high concentrations of GQDs elicited opposite effects on the cytokines production. SB202190, a selective inhibitor of p38 mitogen-activated protein kinase (MAPK), abolished the cytokine-inducing effect of GQDs in macrophages. Moreover, GQDs significantly increased the phosphorylation of p38 MAPK and p65, and promoted the nuclear translocation of nuclear factor-κB (NF-κB). Taken together, these results show that GQDs induce ROS generation, apoptosis, autophagy, and inflammatory response via p38MAPK and NF-κB mediated signaling pathways in THP-1 activated macrophages.

A brief review of exercise, bipolar disorder, and mechanistic pathways.

Despite evidence that exercise has been found to be effective in the treatment of depression, it is unclear whether these data can be extrapolated to bipolar disorder. Available evidence for bipolar disorder is scant, with no existing randomized controlled trials having tested the impact of exercise on depressive, manic or hypomanic symptomatology. Although exercise is often recommended in bipolar disorder, this is based on extrapolation from the unipolar literature, theory and clinical expertise and not empirical evidence. In addition, there are currently no available empirical data on program variables, with practical implications on frequency, intensity and type of exercise derived from unipolar depression studies. The aim of the current paper is to explore the relationship between exercise and bipolar disorder and potential mechanistic pathways. Given the high rate of medical co-morbidities experienced by people with bipolar disorder, it is possible that exercise is a potentially useful and important intervention with regard to general health benefits; however, further research is required to elucidate the impact of exercise on mood symptomology.

Evaluation of nurses' perceptions of the impact of targeted depression education and a screening and referral tool in an acute cardiac setting.

AIMS AND OBJECTIVES: The aim of this study was to evaluate nurses' perceptions of an education programme and screening and referral tool designed for cardiac nurses to facilitate depression screening and referral procedures for patients with coronary heart disease. BACKGROUND: There is a high prevalence of depression in patients with coronary heart disease that is often undetected. It is important therefore that nurses working with cardiac patients are equipped with the knowledge and skills to recognise the signs and symptoms of depression and refer appropriately. DESIGN: A qualitative approach with purposive sampling and semi-structural interviews was implemented within the Donabedian 'Structure-Process-Outcome' evaluation framework. METHODS: Semi-structured interviews were conducted with 14 cardiac nurses working in a major metropolitan hospital six weeks post-attending an education programme on depression and coronary heart disease. Thematic data analysis was implemented, specifically adhering to Halcomb and Davidson's (2006) pragmatic data analysis, to examine nurse knowledge and experience of depression assessment and referral in an acute cardiac ward. RESULTS: The key findings of this study were that the education programme: (1) increased the knowledge base of nurses working with cardiac patients on comorbid depression and coronary heart disease, and (2) assisted in the identification of depression and the referral of 'at risk' patients. CONCLUSIONS: Emphasis was placed on the translational significance of educating cardiac nurses about depression via the introduction of a depression screening and referral instrument designed specifically for use in the cardiac ward. As a result, participants found they were better equipped to identify depressive symptoms and, guided by the screening instrument, to confidently instigate referral procedures. RELEVANCE TO CLINICAL PRACTICE: Much complexity lies in caring for cardiac patients with depression, including issues such as misdiagnosis. Targeted education, including use of appropriate instruments, has the potential to facilitate early recognition of the signs and symptoms of depression in the acute cardiac setting.

Comorbidity between depression and inflammatory bowel disease explained by immune-inflammatory, oxidative, and nitrosative stress; tryptophan catabolite; and gut–brain pathways

The nature of depression has recently been reconceptualized, being conceived as the clinical expression of activated immune-inflammatory, oxidative, and nitrosative stress (IO&NS) pathways, including tryptophan catabolite (TRYCAT), autoimmune, and gut–brain pathways. IO&NS pathways are similarly integral to the pathogenesis of inflammatory bowel disease (IBD). The increased depression prevalence in IBD associates with a lower quality of life and increased morbidity in IBD, highlighting the role of depression in modulating the pathophysiology of IBD.This review covers data within such a wider conceptualization that better explains the heightened co-occurrence of IBD and depression. Common IO&NS underpinning between both disorders is evidenced by increased pro-inflammatory cytokine levels, eg, interleukin-1 (IL-1) and tumor necrosis factor-α, IL-6 trans-signalling; Th-1- and Th-17-like responses; neopterin and soluble IL-2 receptor levels; positive acute phase reactants (haptoglobin and C-reactive protein); lowered levels of negative acute phase reactants (albumin, transferrin, zinc) and anti-inflammatory cytokines (IL-10 and transforming growth factor-β); increased O&NS with damage to lipids, proteinsm and DNA; increased production of nitric oxide (NO) and inducible NO synthase; lowered plasma tryptophan but increased TRYCAT levels; autoimmune responses; and increased bacterial translocation. As such, heightened IO&NS processes in depression overlap with the biological underpinnings of IBD, potentially explaining their increased co-occurrence. This supports the perspective that there is a spectrum of IO&NS disorders that includes depression, both as an emergent comorbidity and as a contributor to IO&NS processes. Such a frame of reference has treatment implications for IBD when “comorbid” with depression.

Pavements and pathways

A one-day interdisciplinary collaborative performance event exploring Mobility and the city. A Deakin-Monash collaboration in which project participants will engage in the interactive remapping of the City in a creative place-making event.

Shaping pathways to gambling consumption? An analysis of the promotion of gambling and non-gambling activities from gambling venues

Background: In Australia, venues which provide gambling activities also provide activities that are utilised by families and children. However, there has been limited theoretical or empirical discussion about whether engagement with non-gambling activities may play a role in shaping pathways to current or future engagement in gambling within these environments. We examined marketing tactics for non-gambling and gambling activities in Clubs. Using this data, we propose a conceptual model to test the role of non-gambling activities within gambling environments in shaping gambling attitudes and consumption intentions.

Methods: This study used a mixed method interpretive content analysis to review the marketing activities on the websites of a sample of 65 registered Clubs in New South Wales, Australia. We identified the extent and nature of techniques used to market gambling and non-gambling activities, particularly non-gambling activities directed towards families and children.

Results: Clubs use various marketing tactics to appeal to families and encourage parents to bring their children into venues. We hypothesise that marketing aimed at bringing children and families into gambling environments may play a role in shaping children’s and adults perceptions of these environments and may be influential in the development of a pathway that increases the likelihood that children will continue to visit these environments as adults, and subsequently the extent to which they engage in gambling later in life.

Conclusions: Future research should explore how the presence of family-friendly activities in Clubs and other venues with gambling activities may play a role in shaping future gambling attitudes and behaviours.