Human relevance of in vivo and in vitro skin irritation tests for hazard classification of pesticides.

Background: Test methods to inform hazard characterization and labeling of pesticides to protect human health are typically conducted using laboratory animals, and for skin irritation/corrosion the rabbit Draize test is currently required by many regulatory agencies. Although the Draize test is generally regarded to provide protective classifications for human health, new approach methodologies (NAMs) have been developed that offer more human relevant models that circumvent the uncertainty associated with species differences that exist between rabbits and humans. Despite wide applicability and use of these test methods across a broad range of chemicals, they have not been widely adopted for testing pesticides and pesticidal formulations. One of the barriers to adoption of these methods in this sector is low concordance with results from the Draize rabbit test, particularly for chemicals within the mild to moderate irritation spectrum.Methods: This review compares and contrasts the extent to which available models used in skin irritation testing mimic the anatomy and physiology of human skin, and how each aligns with the known key events leading to chemically-induced adverse skin irritation and corrosion. Doing so fully characterizes the human relevance of each method.Results: As alternatives to the rabbit Draize test, several protocols using ex vivo, in chemico, and in vitro skin models are available as internationally harmonized test guidelines. These methods rely on a variety of models of human skin, including excised rodent skin, synthetic biochemical models of barrier function, cell culture systems, and reconstructed human tissue models. We find these models exhibit biological and mechanistic relevance aligned with human skin irritation responses. Further, recent retrospective analyses have shown that the reproducibility of the Draize test is less than 50% for mild and moderate responses, with many of the replicate predictions spanning more than one category (e.g., a moderate response reported in one study followed by a non-irritant response reported in another study).Conclusions: Based on this comparative evaluation, we recommend top-down and bottom-up testing strategies that use the most human relevant in vitro test methods for skin irritation and corrosion classification of pesticides and pesticide formulations. To further discriminate among mild and non-irritant formulations, optimization of a cytokine release protocol and subsequent analyses of reference formulation test results is recommended.

A cluster RCT to improve workplace mental health in a policing context: Findings of a mixed-methods implementation evaluation.

BACKGROUND: We conducted a cluster randomized trial of a workplace mental health intervention in an Australian police department. The intervention was co-designed and co-implemented with the police department. Intervention elements included tailored mental health literacy training for all members of participating police stations, and a leadership development and coaching program for station leaders. This study presents the results of a mixed-methods implementation evaluation of the trial. METHODS: Descriptive quantitative analyses characterized the extent of participation in intervention activities, complemented by a qualitative descriptive analysis of transcripts of 60 semistructured interviews with 53 persons and research team field notes. RESULTS: Participation rates in the multicomponent leadership development activities were highly variable, ranging from <10% to approximately 60% across stations. Approximately 50% of leaders and <50% of troops completed the mental health literacy training component of the intervention. Barriers to implementation included rostering challenges, high staff turnover and changes, competing work commitments, staff shortages, limited internal personnel resources to deliver the mental health literacy training, organizational cynicism, confidentiality concerns, and limited communication about the intervention by station command or station champions. Facilitators of participation were also identified, including perceived need for and benefits of the intervention, engagement at various levels, the research team's ability to create buy-in and manage stakeholder relationships, and the use of external, credible leadership development coaches. CONCLUSIONS: Implementation fell far short of expectations. The identified barriers and facilitators should be considered in the design and implementation of similar workplace mental health interventions.

Pathway-based predictive approaches for non-animal assessment of acute inhalation toxicity.

New approaches are needed to assess the effects of inhaled substances on human health. These approaches will be based on mechanisms of toxicity, an understanding of dosimetry, and the use of in silico modeling and in vitro test methods. In order to accelerate wider implementation of such approaches, development of adverse outcome pathways (AOPs) can help identify and address gaps in our understanding of relevant parameters for model input and mechanisms, and optimize non-animal approaches that can be used to investigate key events of toxicity. This paper describes the AOPs and the toolbox of in vitro and in silico models that can be used to assess the key events leading to toxicity following inhalation exposure. Because the optimal testing strategy will vary depending on the substance of interest, here we present a decision tree approach to identify an appropriate non-animal integrated testing strategy that incorporates consideration of a substance's physicochemical properties, relevant mechanisms of toxicity, and available in silico models and in vitro test methods. This decision tree can facilitate standardization of the testing approaches. Case study examples are presented to provide a basis for proof-of-concept testing to illustrate the utility of non-animal approaches to inform hazard identification and risk assessment of humans exposed to inhaled substances.

Hamp1 mRNA and plasma hepcidin levels are influenced by sex and strain but do not predict tissue iron levels in inbred mice.

Iron homeostasis is tightly regulated, and the peptide hormone hepcidin is considered to be a principal regulator of iron metabolism. Previous studies in a limited number of mouse strains found equivocal sex- and strain-dependent differences in mRNA and serum levels of hepcidin and reported conflicting data on the relationship between hepcidin (Hamp1) mRNA levels and iron status. Our aim was to clarify the relationships between strain, sex, and hepcidin expression by examining multiple tissues and the effects of different dietary conditions in multiple inbred strains. Two studies were done: first, Hamp1 mRNA, liver iron, and plasma diferric transferrin levels were measured in 14 inbred strains on a control diet; and second, Hamp1 mRNA and plasma hepcidin levels in both sexes and iron levels in the heart, kidneys, liver, pancreas, and spleen in males were measured in nine inbred/recombinant inbred strains raised on an iron-sufficient or high-iron diet. Both sex and strain have a significant effect on both hepcidin mRNA (primarily a sex effect) and plasma hepcidin levels (primarily a strain effect). However, liver iron and diferric transferrin levels are not predictors of Hamp1 mRNA levels in mice fed iron-sufficient or high-iron diets, nor are the Hamp1 mRNA and plasma hepcidin levels good predictors of tissue iron levels, at least in males. We also measured plasma erythroferrone, performed RNA-sequencing analysis of liver samples from six inbred strains fed the iron-sufficient, low-iron, or high-iron diets, and explored differences in gene expression between the strains with the highest and lowest hepcidin levels.NEW & NOTEWORTHY Both sex and strain have a significant effect on both hepcidin mRNA (primarily a sex effect) and plasma hepcidin levels (primarily a strain effect). Liver iron and diferric transferrin levels are not predictors of Hamp1 mRNA levels in mice, nor are the Hamp1 mRNA and plasma hepcidin levels good predictors of tissue iron levels, at least in males.

The work-based predictors of job engagement and job satisfaction experienced by community health professionals.

BACKGROUND: Job engagement represents a critical resource for community-based health care agencies to achieve high levels of effectiveness. However, studies examining the organizational sources of job engagement among health care professionals have generally overlooked those workers based in community settings. PURPOSE: This study drew on the demand-control model, in addition to stressors that are more specific to community health services (e.g., unrewarding management practices), to identify conditions that are closely associated with the engagement experienced by a community health workforce. Job satisfaction was also included as a way of assessing how the predictors of job engagement differ from those associated with other job attitudes. METHODOLOGY/APPROACH: Health and allied health care professionals (n = 516) from two Australian community health services took part in the current investigation. Responses from the two organizations were pooled and analyzed using linear multiple regression. FINDINGS: The analyses revealed that three working conditions were predictive of both job engagement and job satisfaction (i.e., job control, quantitative demands, and unrewarding management practices). There was some evidence of differential effects with cognitive demands being associated with job engagement, but not job satisfaction. PRACTICE IMPLICATIONS: The results provide important insights into the working conditions that, if addressed, could play key roles in building a more engaged and satisfied community health workforce. Furthermore, working conditions like job control and management practices are amenable to change and thus represent important areas where community health services could enhance the energetic and motivational resources of their employees.

Psychosocial Working Conditions and Suicide Ideation: Evidence From a Cross-Sectional Survey of Working Australians.

OBJECTIVES: This study examined the relationship between psychosocial working factors such as job control, job demands, job insecurity, supervisor support, and workplace bullying as risk factors for suicide ideation. METHODS: We used a logistic analytic approach to assess risk factors for thoughts of suicide in a cross-sectional sample of working Australians. Potential predictors included psychosocial job stressors (described above); we also controlled for age, gender, occupational skill level, and psychological distress. RESULTS: We found that workplace bullying or harassment was associated with 1.54 greater odds of suicide ideation (95% confidence interval 1.64 to 2.05) in the model including psychological distress. Results also suggest that higher job control and security were associated with lower odds of suicide ideation. CONCLUSIONS: These results suggest the need for organizational level intervention to address psychosocial job stressors, including bullying.

An integrated workplace mental health intervention in a policing context: Protocol for a cluster randomised control trial.

BACKGROUND: In this paper, we present the protocol for a cluster-randomised trial to evaluate the implementation and effectiveness of a workplace mental health intervention in the state-wide police department of the south-eastern Australian state of Victoria. n. The primary aims of the intervention are to improve psychosocial working conditions and mental health literacy, and secondarily to improve mental health and organisational outcomes. METHODS/DESIGN: The intervention was designed collaboratively with Victoria Police based on a mixed methods pilot study, and combines multi-session leadership coaching for the senior officers within stations (e.g., Sergeants, Senior Sergeants) with tailored mental health literacy training for lower and upper ranks. Intervention effectiveness will be evaluated using a two-arm cluster-randomised trial design, with 12 police stations randomly assigned to the intervention and 12 to the non-intervention/usual care control condition. Data will be collected from all police members in each station (estimated at >20 per station). Psychosocial working conditions (e.g., supervisory support, job control, job demands), mental health literacy (e.g., knowledge, confidence in assisting someone who may have a mental health problem), and mental health will be assessed using validated measures. Organisational outcomes will include organisational depression disclosure norms, organisational cynicism, and station-level sickness absence rates. The trial will be conducted following CONSORT guidelines. Identifying data will not be collected in order to protect participant privacy and to optimise participation, hence changes in primary and secondary outcomes will be assessed using a two-sample t-test comparing summary measures by arm, with weighting by cluster size. DISCUSSION: This intervention is novel in its integration of stressor-reduction and mental health literacy-enhancing strategies. Effectiveness will be rigorously evaluated, and if positive results are observed, the intervention will be adapted across Victoria Police (total employees ~16,500) as well as possibly in other policing contexts, both nationally and internationally. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN82041334. Registered 24th July, 2014.

Psychosocial job quality, mental health, and subjective wellbeing: a cross-sectional analysis of the baseline wave of the Australian Longitudinal Study on Male Health.

BACKGROUND: Employment status and working conditions are strong determinants of male health, and are therefore an important focus in the Australian Longitudinal Study on Male Health (Ten to Men). In this paper, we describe key work variables included in Ten to Men, and present analyses relating psychosocial job quality to mental health and subjective wellbeing at baseline. METHODS: A national sample of males aged 10 to 55 years residing in private dwellings was drawn using a stratified multi-stage cluster random sample design. Data were collected between October 2013 and July 2014 for a cohort of 15,988 males, representing a response fraction of 35 %. This analysis was restricted to 18-55 year old working age participants (n = 13,456). Work-related measures included employment status, and, for those who were employed, a number of working conditions including an ordinal scale of psychosocial job quality (presence of low job control, high demand and complexity, high job insecurity, and low fairness of pay), and working time-related stressors such as long working hours and night shift work. Associations between psychosocial job quality and two outcome measures, mental ill-health and subjective wellbeing, were assessed using multiple linear regression. RESULTS: The majority of participants aged 18-55 years were employed at baseline (85.6 %), with 8.4 % unemployed and looking for work, and 6.1 % not in the labour force. Among employed participants, there was a high prevalence of long working hours (49.9 % reported working more than 40 h/week) and night shift work (23.4 %). Psychosocial job quality (exposure to 0/1/2/3+ job stressors) prevalence was 36 %/ 37 %/ 20 %/ and 7 % of the working respondents. There was a dose-response relationship between psychosocial job quality and each of the two outcome measures of mental health and subjective wellbeing after adjusting for potential confounders, with higher magnitude associations between psychosocial job quality and subjective wellbeing. CONCLUSIONS: These results extend the study of psychosocial job quality to demonstrate associations with a global measure of subjective wellbeing. Ten to Men represents a valuable new resource for the longitudinal and life course study of work and health in the Australian male population.

Climate and soil properties limit the positive effects of land use reversion on carbon storage in Eastern Australia.

Australia's "Direct Action" climate change policy relies on purchasing greenhouse gas abatement from projects undertaking approved abatement activities. Management of soil organic carbon (SOC) in agricultural soils is an approved activity, based on the expectation that land use change can deliver significant changes in SOC. However, there are concerns that climate, topography and soil texture will limit changes in SOC stocks. This work analyses data from 1482 sites surveyed across the major agricultural regions of Eastern Australia to determine the relative importance of land use vs. other drivers of SOC. Variation in land use explained only 1.4% of the total variation in SOC, with aridity and soil texture the main regulators of SOC stock under different land uses. Results suggest the greatest potential for increasing SOC stocks in Eastern Australian agricultural regions lies in converting from cropping to pasture on heavy textured soils in the humid regions.

Workplace suicide prevention: a systematic review of published and unpublished activities.

There are a number of published studies on workplace suicide prevention activities, and an even larger number of activities that are not reported on in academic literature. The aim of this review was to provide a systematic assessment of workplace suicide prevention activities, including short-term training activities, as well as suicide prevention strategies designed for occupational groups at risk of suicide. The search was based on Meta-analysis of Observational Studies in Epidemiology (MOOSE) Guidelines. The databases used for the searches were the Cochrane Trials Library and PubMed. A range of suicide prevention websites were also searched to ascertain the information on unpublished workplace suicide prevention activities. Key characteristics of retrieved studies were extracted and explained, including whether activities were short-term training programmes or developed specifically for occupations at risk of suicide. There were 13 interventions relevant for the review after exclusions. There were a few examples of prevention activities developed for at-risk occupations (e.g. police, army, air force and the construction industry) as well as a number of general awareness programmes that could be applied across different settings. Very few workplace suicide prevention initiatives had been evaluated. Results from those that had been evaluated suggest that prevention initiatives had beneficial effects. Suicide prevention has the potential to be integrated into existing workplace mental health activities. There is a need for further studies to develop, implement and evaluate workplace suicide prevention programmes.

Workplace stress: what is the role of positive mental health?

OBJECTIVE: To examine whether positive mental health (PMH)-a positively focused well-being construct-moderates the job stress-distress relationship. METHODS: Longitudinal regression was used to test two waves of matched, population-level data from a sample of older, working Australian adults (n = 3291) to see whether PMH modified the relationship between work stress and later psychological distress. RESULTS: Time 1 work stress was positively associated with distress at both time points. Positive mental health was negatively associated with work stress at both time points. Positive mental health modified the impact of work stress on psychological distress. This effect only occurred for those with the highest levels of PMH. CONCLUSIONS: Positive mental health may help protect workers from the effect of workplace stress but only in a small proportion of the population. Therefore, to improve workplace mental health, workplaces need to both prevent stress and promote PMH.

Workplace mental health: developing an integrated intervention approach.

BACKGROUND: Mental health problems are prevalent and costly in working populations. Workplace interventions to address common mental health problems have evolved relatively independently along three main threads or disciplinary traditions: medicine, public health, and psychology. In this Debate piece, we argue that these three threads need to be integrated to optimise the prevention of mental health problems in working populations. DISCUSSION: To realise the greatest population mental health benefits, workplace mental health intervention needs to comprehensively 1) protect mental health by reducing work-related risk factors for mental health problems; 2) promote mental health by developing the positive aspects of work as well as worker strengths and positive capacities; and 3) address mental health problems among working people regardless of cause. We outline the evidence supporting such an integrated intervention approach and consider the research agenda and policy developments needed to move towards this goal, and propose the notion of integrated workplace mental health literacy. SUMMARY: An integrated approach to workplace mental health combines the strengths of medicine, public health, and psychology, and has the potential to optimise both the prevention and management of mental health problems in the workplace.

Stakeholder perceptions of job stress in an industrialized country: implications for policy and practice.

We used a secondary, qualitative analysis of stakeholder perceptions of work stress in Australia to characterize the context for policy and practice intervention. Themes included: Individual versus contextual descriptions of stress; perceived 'gender' differences in manifesting and reporting of stress; the work/home interface; and perceived sectoral and occupational differences in compensation claim rates. We found that people often still perceive stress as an individual rather than organizational problem and view work stress as a stereotypically feminine weakness that affects only certain people. Organizations downplay and overlook risks, increasing worker reluctance to report stressors, creating barriers to job stress interventions. Our study may be relevant to other industrial countries where researchers currently study job stress interventions to improve their effectiveness. Comprehensive approaches can increase knowledge and decrease stigma about job stress and mental illness, and target both work- and non-work-related influences on mental health.

Aluminium exposure disrupts elemental homeostasis in Caenorhabditis elegans.

Aluminium (Al) is highly abundant in the environment and can elicit a variety of toxic responses in biological systems. Here we characterize the effects of Al on Caenorhabditis elegans by identifying phenotypic abnormalities and disruption in whole-body metal homeostasis (metallostasis) following Al exposure in food. Widespread changes to the elemental content of adult nematodes were observed when chronically exposed to Al from the first larval stage (L1). Specifically, we saw increased barium, chromium, copper and iron content, and a reduction in calcium levels. Lifespan was decreased in worms exposed to low levels of Al, but unexpectedly increased when the Al concentration reached higher levels (4.8 mM). This bi-phasic phenotype was only observed when Al exposure occurred during development, as lifespan was unaffected by Al exposure during adulthood. Lower levels of Al slowed C. elegans developmental progression, and reduced hermaphrodite self-fertility and adult body size. Significant developmental delay was observed even when Al exposure was restricted to embryogenesis. Similar changes in Al have been noted in association with Al toxicity in humans and other mammals, suggesting that C. elegans may be of use as a model for understanding the mechanisms of Al toxicity in mammalian systems.

The Caenorhabditis elegans K10C2.4 gene encodes a member of the fumarylacetoacetate hydrolase family: a Caenorhabditis elegans model of type I tyrosinemia.

In eukaryotes and many bacteria, tyrosine is degraded to produce energy via a five-step tyrosine degradation pathway. Mutations affecting the tyrosine degradation pathway are also of medical importance as mutations affecting enzymes in the pathway are responsible for type I, type II, and type III tyrosinemia. The most severe of these is type I tyrosinemia, which is caused by mutations affecting the last enzyme in the pathway, fumarylacetoacetate hydrolase (FAH). So far, tyrosine degradation in the nematode Caenorhabditis elegans has not been studied; however, genes predicted to encode enzymes in this pathway have been identified in several microarray, proteomic, and RNA interference (RNAi) screens as perhaps being involved in aging and the control of protein folding. We sought to identify and characterize the genes in the worm tyrosine degradation pathway as an initial step in understanding these findings. Here we describe the characterization of the K10C2.4, which encodes a homolog of FAH. RNAi directed against K10C2.4 produces a lethal phenotype consisting of death in young adulthood, extensive damage to the intestine, impaired fertility, and activation of oxidative stress and endoplasmic stress response pathways. This phenotype is due to alterations in tyrosine metabolism as increases in dietary tyrosine enhance it, and inhibition of upstream enzymes in tyrosine degradation with RNAi or genetic mutations reduces the phenotype. We also use our model to identify genes that suppress the damage produced by K10C2.4 RNAi in a pilot genetic screen. Our results establish worms as a model for the study of type I tyrosinemia.