Clusterin is a critical downstream mediator of stress-induced YB-1 transactivation in prostate cancer

Clusterin is a stress-activated, cytoprotective chaperone that confers broad-spectrum treatment resistance in cancer. However, the molecular mechanisms mediating CLU transcription following anticancer treatment stress remain incompletely defined. We report that Y-box binding protein-1 (YB-1) directly binds to CLU promoter regions to transcriptionally regulate clusterin expression. In response to endoplasmic reticulum stress inducers, including paclitaxel, YB-1 is translocated to the nucleus to transactivate clusterin. Furthermore, higher levels of activated YB-1 and clusterin are seen in taxane-resistant, compared with parental, prostate cancer cells. Knockdown of either YB-1 or clusterin sensitized prostate cancer cells to paclitaxel, whereas their overexpression increased resistance to taxane. Clusterin overexpression rescued cells from increased paclitaxel-induced apoptosis following YB-1 knockdown; in contrast, however, YB-1 overexpression did not rescue cells from increased paclitaxel-induced apoptosis following clusterin knockdown. Collectively, these data indicate that YB-1 transactivation of clusterin in response to stress is a critical mediator of paclitaxel resistance in prostate cancer. Mol Cancer Res; 9(12); 1755–66.

A multilevel investigation of inequalities in clinical and psychosocial outcomes for women after breast cancer

Background In Australia, breast cancer is the most common cancer affecting Australian women. Inequalities in clinical and psychosocial outcomes have existed for some time, affecting particularly women from rural areas and from areas of disadvantage. We have a limited understanding of how individual and area-level factors are related to each other, and their associations with survival and other clinical and psychosocial outcomes. Methods/Design This study will examine associations between breast cancer recurrence, survival and psychosocial outcomes (e.g. distress, unmet supportive care needs, quality of life). The study will use an innovative multilevel approach using area-level factors simultaneously with detailed individual-level factors to assess the relative importance of remoteness, socioeconomic and demographic factors, diagnostic and treatment pathways and processes, and supportive care utilization to clinical and psychosocial outcomes. The study will use telephone and self-administered questionnaires to collect individual-level data from approximately 3, 300 women ascertained from the Queensland Cancer Registry diagnosed with invasive breast cancer residing in 478 Statistical Local Areas Queensland in 2011 and 2012. Area-level data will be sourced from the Australian Bureau of Statistics census data. Geo-coding and spatial technology will be used to calculate road travel distances from patients' residence to diagnostic and treatment centres. Data analysis will include a combination of standard empirical procedures and multilevel modelling. Discussion The study will address the critical question of: what are the individual- or area-level factors associated with inequalities in outcomes from breast cancer? The findings will provide health care providers and policy makers with targeted information to improve the management of women with breast cancer, and inform the development of strategies to improve psychosocial care for women with breast cancer.

Regional and remote airports under stress in Australia

Australia's airline industry was born on connecting regional communities to major cities, but almost a century later, many regional and remote communities are facing the prospect of losing their air transport services. The focus of this paper is to highlight key issues and concerns surrounding remote, rural and regional airports in Australia using a network governance framework. Contributions are focused towards regional and remote airport managers, decision makers, and policy makers to stimulate further discussion towards retaining regional and remote services to communities.

Stress at work : a new theoretical framework for psychologists

This paper examines the way psychologists and others in teh helping professions can deal with stressors in their lives and still work effectively. Three questions will be asked. First "What are the essential ingredients of an environment that supports psychologists going through personal stressors? Second, "What are the personal characteristics and strategies that give resilience to a professional during this period?" and third,"How does the stressor or grieving process influence a psychologist's therapy?" The whole will be fitted into a visual framework and the interaction of the three main variables (client, therapist and stressor) will be explored.

Educational stress among Chinese adolescents : measurement, risk factors and associations with mental health

Academic pressure among adolescents is a major risk factor for poor mental health and suicide and other harmful behaviours. While this is a worldwide phenomenon, it appears to be especially pronounced in China and other East Asian countries. Despite a growing body of research into adolescent mental health in recent years, the multiple constructs within the ‘educational stress’ phenomenon have not been clearly articulated in Chinese contexts. Further, the individual, family, school and peer influencing factors for educational stress and its associations with adolescent mental health are not well understood. An in-depth investigation may provide important information for the ongoing educational reform in Mainland China with a special focus on students’ mental health and wellbeing. The primary goal of this study was to examine the relative contribution of educational stress to poor mental health, in comparison to other well-known individual, family, school and peer factors. Another important task was to identify significant risk factors for educational stress. In addition, due to the lack of a culturally suitable instrument for educational stress in this population, a new tool – the Educational Stress Scale for Adolescents (ESSA) was initially developed in this study and tested for reliability and validity. A self-administered questionnaire was used to collect information from convenient samples of secondary school students in Shandong, China. The pilot survey was conducted with 347 students (grades 8 and 11) to test the psychometric properties of the ESSA and other scales or questions in the questionnaire. Based on factor analysis and reliability and validity testing, the 16-item scale (the ESSA) with five factors showed adequate to good internal consistency, 2-week test-retest reliability, and satisfactory concurrent and predictive validity. Its factor structure was further demonstrated in the main survey with a confirmatory factor analysis illustrating a good fit of the proposed model based on a confirmatory factor analysis. The reliabilities of other scales and questions were also adequate to be used in this study. The main survey was subsequently conducted with a sample of 1627 secondary school (grades 7-12) students to examine the influencing factors of educational stress and its associations with mental health outcomes, including depression, happiness and suicidal behaviours. A wide range of individual, family, school and peer factors were found to have a significant association with the total ESSA and subscale scores. Most of the strong factors for academic stress were school or study-related, including rural school location, low school connectedness, perceived poor academic grades and frequent emotional conflicts with teachers and peers. Unexpectedly, family and parental factors, such as parental bonding, family connectedness and conflicts with parents were found to have little or no association with educational stress. Educational stress was the most predictive variable for depression, but was not strongly associated with happiness. It had a strong association with suicide ideation but not with suicide attempts. Among five subscales of the ESSA, ‘Study despondency’ score had the strongest associations with these mental health measures. Surprising, two subscales, ‘Self-expectation’ and ‘Worry about grades’ showed a protective effect on suicidal behaviours. An additional analysis revealed that although academic pressure was the most commonly reported reason for suicidal thinking, the occurrence of problems in peer relationships such as peer teasing and bullying, and romantic problems had a much stronger relationship with actual attempts. This study provides some insights into the nature and health implications of educational stress among Chinese adolescents. Findings in this study suggest that interventions on educational stress should focus on school environment and academic factors. Intervention programs focused on educational stress may have a high impact on the prevalence of common mental disorders such as depression. Efforts to increase perceived happiness however should cover a wider range of individual, family and school factors. The importance of healthy peer relationships should be adequately emphasised in suicide prevention. In addition, the newly developed scale (the ESSA) demonstrates sound psychometric properties and is expected to be used in future research into academic-related stress among secondary school adolescents.

Victims’ perceptions of traditional and cyberbullying, and the psychosocial correlates of their victimisation

It is well recognised that there are serious correlates for victims of traditional bullying. These have been shown to include increased levels of depression, anxiety and psychosomatic symptoms, in addition to often severe physical harm and even suicide. Bullied students also feel more socially ineffective; have greater interpersonal difficulties, together with higher absenteeism from school and lower academic competence. In the emerging field of cyberbullying many researchers have hypothesised a greater impact and more severe consequences for victims because of the 24/7 nature and the possibility of the wider audience with this form of bullying. However, to date there is scarce empirical evidence to support this. This study sought to compare victims’ perceptions of the harshness and impact of bullying by traditional and cyber means. The major findings showed that although students who had been victimised by traditional bullying reported that they felt their bullying was harsher, crueller and had more impact on their lives than those students who had been cyberbullied, the correlates of their mental health revealed that cyber victims reported significantly more social difficulties, higher anxiety levels and depression than traditional victims. The implications for school counsellors and mental health workers are discussed.

The delta opioid receptor antagonist, SoRI-9409, decreases yohimbine stress-induced reinstatement of ethanol-seeking

A major problem in treating alcohol use disorders (AUDs) is the high rate of relapse due to stress and re-exposure to cues or an environment previously associated with alcohol use. Stressors can induce relapse to alcohol-seeking in humans or reinstatement in rodents. Delta opioid peptide receptors (DOP-Rs) play a role in cue-induced reinstatement of ethanol-seeking; however, their role in stress-induced reinstatement of ethanol-seeking is not known. The objective of this study was to determine the role of DOP-Rs in yohimbine-stress-induced reinstatement of ethanol-seeking. Male, Long-Evans rats were trained to self-administer 10% ethanol in daily 30-minute operant self-administration sessions using a FR3 schedule of reinforcement, followed by extinction training. Once extinction criteria were met, we examined the effects of the DOP-R antagonist, SoRI-9409 (0–5 mg/kg, i.p.) on yohimbine (2 mg/kg, i.p.) stress-induced reinstatement. Additionally, DOP-R-stimulated [35S]GTPS binding was measured in brain membranes and plasma levels of corticosterone (CORT) were determined. Pre-treatment with SoRI-9409 decreased yohimbine stress-induced reinstatement of ethanol-seeking but did not affect yohimbine-induced increases in plasma CORT levels. Additionally, yohimbine increased DOP-R-stimulated 35[S]GTPS binding in brain membranes of ethanol-trained rats, an effect that was inhibited by SoRI-9409. This suggests that the DOP-R plays an important role in yohimbine-stress-induced reinstatement of ethanol-seeking behavior, and DOP-R antagonists may be promising candidates for further development as a treatment for AUDs.

Stress and addiction : contribution of the corticotropin releasing factor (CRF) system in neuroplasticity

Corticotropin releasing factor (CRF) has been shown to induce various behavioral changes related to adaptation to stress. Dysregulation of the CRF system at any point can lead to a variety of psychiatric disorders, including substance use disorders (SUDs). CRF has been associated with stress-induced drug reinforcement. Extensive literature has identified CRF to play an important role in the molecular mechanisms that lead to an increase in susceptibility that precipitates relapse to SUDs. The CRF system has a heterogeneous role in SUDs. It enhances the acute effects of drugs of abuse and is also responsible for the potentiation of drug-induced neuroplasticity evoked during the withdrawal period. We present in this review the brain regions and circuitries where CRF is expressed and may participate in stress-induced drug abuse. Finally, we attempt to evaluate the role of modulating the CRF system as a possible therapeutic strategy for treating the dysregulation of emotional behaviors that result from the acute positive reinforcement of substances of abuse as well as the negative reinforcement produced by withdrawal.

Academic stress among adolescents in China

Pressure from study has long been identified as a significant contributor to many mental health problems in school children and adolescents. Students are often stressed by heavy workload, high academic expectation and dissatisfaction with their grades. Excessive amount of this special type of stress (academic stress or educational stress) may then lead to severe psychological symptoms, such as depressed mood, anxious feelings and even suicide thoughts and acts when coping recourses are exhausted. Chinese students are believed to have high academic burden and pressure due to high expectations of their parents and fierce competitions with their peers. Knowledge of the nature and health effects of academic stress may be useful to inform quality education and mental health promotions. This review aims to provide a comprehensive analysis of reported literature regarding educational stress and its relationships with mental health problems worldwide and the current research progress in Chinese adolescents, and to provide directions for future research into this topic in Chinese adolescent populations.

Educational stress among Chinese adolescents : individual, family, school and peer influences

Educational stress is common among school children and adolescents, especially in Asian countries. This study aims to identify factors associated with perceived educational stress among students in China. A cross-sectional questionnaire survey was conducted with 1627 students (Grades 7–12) from six secondary schools in rural and urban areas of Shandong Province. A wide range of individual, family, school and peer factors were associated with stress measured using the Educational Stress Scale for Adolescents (ESSA). Rural school location, low school connectedness, perceived poor academic grades, female gender, older age and frequent emotional conflicts with teachers and peers were among the strongest correlates, and most of them are school- or study-related. Unexpectedly, family and parental factors were found to have little or no association with children’s perceived educational stress. These findings may offer directions for interventions in secondary school settings.

Assessing occupational stress in psychiatric nurses using the full job strain model the value of social support to nurses

The present research examined the effects of occupational stress in psychiatric nursing on employee well!being using the full Job Strain Model.The Job Strain Model was assessed for its ability to predict employee well!being in terms of job satisfaction and mental health. The original Job Strain Model was expanded to include social support based on previous research concerning the impact of social support on well!being[ In the present study\ both work support and non-work were assessed for their contribution to wellbeing.The results of this study indicate that the full Job Strain Model can be used to significantly predict job satisfaction and mental health in this sample of Australian psychiatric nurses. Furthermore social support was shown to be an important component of the Job Strain Model.