The deleterious effects of oxidative and nitrosative stress on palmitoylation, membrane lipid rafts and lipid-based cellular signalling : new drug targets in neuroimmune disorders

Oxidative and nitrosative stress (O&NS) is causatively implicated in the pathogenesis of Alzheimer’s and Parkinson’s disease, multiple sclerosis, chronic fatigue syndrome, schizophrenia and depression. Many of the consequences stemming from O&NS, including damage to proteins, lipids and DNA, are well known, whereas the effects of O&NS on lipoprotein-based cellular signalling involving palmitoylation and plasma membrane lipid rafts are less well documented. The aim of this narrative review is to discuss the mechanisms involved in lipid-based signalling, including palmitoylation, membrane/lipid raft (MLR) and n-3 polyunsaturated fatty acid (PUFA) functions, the effects of O&NS processes on these processes and their role in the abovementioned diseases. S-palmitoylation is a post-translational modification, which regulates protein trafficking and association with the plasma membrane, protein subcellular location and functions. Palmitoylation and MRLs play a key role in neuronal functions, including glutamatergic neurotransmission, and immune-inflammatory responses. Palmitoylation, MLRs and n-3 PUFAs are vulnerable to the corruptive effects of O&NS. Chronic O&NS inhibits palmitoylation and causes profound changes in lipid membrane composition, e.g. n-3 PUFA depletion, increased membrane permeability and reduced fluidity, which together lead to disorders in intracellular signal transduction, receptor dysfunction and increased neurotoxicity. Disruption of lipid-based signalling is a source of the neuroimmune disorders involved in the pathophysiology of the abovementioned diseases. n-3 PUFA supplementation is a rational therapeutic approach targeting disruptions in lipid-based signalling.

Hair cortisol levels, perceived stress and body mass index in women and children living in socioeconomically disadvantaged neighborhoods: the READI study

Disadvantaged communities provide adverse psychosocial exposures that have been linked to high levels of stress, and this may provide one explanatory pathway linking socioeconomic disadvantage to obesity. This study used hair cortisol analysis to quantify associations between stress and body mass index (BMI), and between hair cortisol and perceived psychological stress levels, in women and children living in socioeconomically disadvantaged neighborhoods. Participants were a volunteer sample of 70 women from the Resilience for Eating and Activity Despite Inequality study, including 30 maternal-child pairs. Women self-reported body weight, height and perceived psychological stress using the Perceived Stress Scale (PSS), and provided hair samples for themselves and their child. Children's body weight and height were measured. Following extraction, hair cortisol levels were measured using enzyme-linked immunosorbent assay. Multiple linear regression models examined associations between stress and BMI, and between hair cortisol and perceived stress levels in women and children. Women's hair cortisol levels were not associated with their BMI or PSS scores. Women's PSS scores were positively associated with their BMI (p = 0.015). Within maternal-child pairs, mothers and children's hair cortisol levels were strongly positively associated (p = 0.006). Maternal hair cortisol levels and PSS scores were unrelated to their child's zBMI. Children's hair cortisol levels were not associated with their zBMI or with their mother's PSS score. Findings suggest that cortisol-based and perceived psychological measures of stress may be distinct among women and children living in disadvantaged neighborhoods. Perceived psychological measures may be more important predictors of weight-related risk.

Health service use and costs for infant behaviour problems and maternal stress

AIM: We aim to describe health service (HS) use in the first 6 months post-partum and to examine the associations between service costs, infant behaviour and maternal depressive symptoms. METHODS: Participants were 781 infants and mothers in Melbourne, Australia. Mothers reported infant feeding, sleeping and crying problems, depressive symptoms and health service use. Costs were valued in 2012 Australian dollars. RESULTS: The most common services used were maternal child health nurses, general practitioners (GP) and allied health. Infant feeding problems were associated with increased costs for services relevant to infant behaviour including maternal child health nurses (P = 0.007), GP (P = 0.008) and paediatricians (P = 0.03). Maternal depressive symptoms were associated with increased costs for services relevant to depressive symptoms including parenting centres (P = 0.04), GP (P = 0.004), psychiatrists (P = 0.02) and psychologists (P = 0.001). Mothers who completed high school had higher service costs for infant problems than those with lower education (P = 0.02). Single mothers had higher costs for services used for their depressive symptoms than partnered mothers (P < 0.001). Mothers with English as a second language had lower service costs for their depressive symptoms (P = 0.02). CONCLUSIONS: Infant feeding problems and maternal depressive symptoms are associated with higher costs for health services relevant to these conditions. Cost-effective strategies to manage these conditions are needed with accessibility being ensured for mothers who are experiencing social adversity.

An inverse routine to predict residual stress in sheet material

A method is presented to determine residual stress distribution in sheet material from data collected in a free bending test. It may be used where the residual stress distribution is symmetrical about the mid-surface as it is usually the case for frequently-used sheet metal post-processing techniques such as skin-pass or temper rolling, tension- and roller leveling. An existing inverse technique is used to obtain a residual stress profile and material constants that provide the best fit in a finite element analysis of bending with the experimentally derived moment-curvature relation. The method is verified for bending of a low-carbon stainless steel using measurement of residual stress by X-ray diffraction. The residual stresses were induced in the sheet by cold rolling. The technique described here can be used industrially as a rapid method of investigating residual stresses in incoming sheet. In processes where the deformation is principally one of bending, such as cold roll forming, it is known that residual stresses have an influence on shape defects and springback and the method presented here can be used to determine whether incoming sheet is suitable for further processing and also as a means of obtaining improved material data input for numerical simulation.

Enterprise resource planning and the post bureaucratic organization

Purpose – The purpose of the paper is to use a case study setting involving the implementation of an enterprise resource planning (ERP) system to expose and analyze the conflicts in the characterizations of the post bureaucratic organisation (PBO) in the literature. ERP implementations are often accompanied by increasing levels of stress in organizations that place pressures on organizational relationships and structures. Additionally, ERPs are regarded as introducing their own techno-logic of centralization, standardization and formalization that provides an apparent contrast to the exhortations about employee empowerment.Design/methodology/approach – A case study of ERP implementation in a medium-sized entity is presented. The paper explores aspects of ERP and PBO from the context of postmodern organization theory.Findings – Some concerns about PBO identified in the literature are reflected in the case situation. For example, there is a commitment to give up private time and work flexibly by some employees. The paper also provides evidence of the way the management team substitute their reliance on a key individual knowledge worker for that of an ERP system and external vendor support. Paradoxically, trust in that same knowledge worker and between core users of the system is essential to enable the implementation of the system.

The Post-Anaesthesia N-acetylcysteine Cognitive Evaluation (PANACEA) trial: study protocol for a randomised controlled trial

BACKGROUND: Some degree of cognitive decline after surgery occurs in as many as one quarter of elderly surgical patients, and this decline is associated with increased morbidity and mortality. Cognition may be affected across a range of domains, including memory, psychomotor skills, and executive function. Whilst the exact mechanisms of cognitive change after surgery are not precisely known, oxidative stress and subsequent neuroinflammation have been implicated. N-acetylcysteine (NAC) acts via multiple interrelated mechanisms to influence oxidative homeostasis, neuronal transmission, and inflammation. NAC has been shown to reduce oxidative stress and inflammation in both human and animal models. There is clinical evidence to suggest that NAC may be beneficial in preventing the cognitive decline associated with both acute physiological insults and dementia-related disorders. To date, no trials have examined perioperative NAC as a potential moderator of postoperative cognitive changes in the noncardiac surgery setting.

METHODS AND DESIGN: This is a single-centre, randomised, double-blind, placebo-controlled clinical trial, with a between-group, repeated-measures, longitudinal design. The study will recruit 370 noncardiac surgical patients at the University Hospital Geelong, aged 60 years or older. Participants are randomly assigned to receive either NAC or placebo (1:1 ratio), and groups are stratified by age and surgery type. Participants undergo a series of neuropsychological tests prior to surgery, 7 days, 3 months, and 12 months post surgery. It is hypothesised that the perioperative administration of NAC will reduce the degree of postoperative cognitive changes at early and long-term follow-up, as measured by changes on individual measures of the neurocognitive battery, when compared with placebo. Serum samples are taken on the day of surgery and on day 2 post surgery to quantitate any changes in levels of biomarkers of inflammation and oxidative stress.

DISCUSSION: The PANACEA trial aims to examine the potential efficacy of perioperative NAC to reduce the severity of postoperative cognitive dysfunction in an elderly, noncardiac surgery population. This is an entirely novel approach to the prevention of postoperative cognitive dysfunction and will have high impact and translatable outcomes if NAC is found to be beneficial.

What reading and writing trauma fiction illuminates about post-traumatic growth.

Angelina Mirabito's PhD in Creative Writing investigated the therapeutic value of reading and writing trauma fiction. Her findings show that it is possible for adult survivors of complex trauma to experience post-traumatic growth from writing an adult survivor of childhood trauma coming of age story.

Traumatic stress in parents of children with autism spectrum disorder.

A traumatic stress framework was identified as a valid way of conceptualising high levels of parenting stress in a subpopulation of parents raising a child with autism. An association between traumatic stress symptoms and child behaviours that posed a threat to child safety (e.g., elopement, aggression, self-injury) was found.