Worker-fatigue contributing to workplace incidents in New Zealand Forestry.

PROBLEM: Reports of incidents in dangerous work environments can be analysed to identify common hazards, in turn aiding in the prevention of future accidents. Whilst studies exist that do this, most focus on causes that involve physical risks. In this paper we propose an alternative approach, and illustrate causes of forestry incidents from the perspective of worker-failure and fatigue. METHOD: This paper outlines the analysis of eight years' worth of New Zealand forestry incident data, with a focus on the cause of, and time that, incidents occur. RESULTS: This has resulted in two main findings. First, 70% of incidents can be attributed, at least in part, to worker-failures. Second, 78% of worker-failure based causes show indications of fatigue. This indicates that a significant number of forestry incidents are caused by worker-fatigue. Finally, this dataset showed inconsistencies in data quality, similar to those that exist in other datasets. This did not affect our analysis. However, these types of errors have the potential to affect the data quality in the national reporting system. IMPACT ON INDUSTRY: The results from this study will be used in a larger project on detecting fatigue in forestry workers for injury and incident prevention. It is also our hope that other researchers may find these results of interest for further fatigue prevention research in hazardous industries.

Effect of systemic transplantation of bone marrow-derived mesenchymal stem cells on neuropathology markers in APP/PS1 Alzheimer mice.

AIMS: Mesenchymal stem cells (MSC) have recently attracted interest as a potential basis for a cell-based therapy of AD. We investigated the putative immune-modulatory effects in neuroinflammation of systemic transplantation of MSC into APP/PS1 transgenic mice. METHODS: 106 MSC were injected into APP/PS1 mice via the tail vein and histological analysis was performed for microglia and amyloid (pE3-Aß) plaque numbers, glial distribution and pE3-Aß plaque size. In addition, a biochemical analysis by qPCR for pro-inflammatory, chemoattractant and neurotrophic factors was performed. RESULTS: MSC are associated with pE3-Aß plaques. The effects of transplantation on microglia-associated pathology could be observed after 28 days. Animals showed a reduction in microglial numbers in the cortex and in microglia size. Gene expression was reduced for TNF-α, IL-6, MCP-1, and for NGF, in MSC recipients. Also, we investigated for the first time and found no changes in expression of IL-10, CCR5, BDNF, VEGF and IFNγ. PTGER2 expression levels were increased in the hippocampus but were reduced in the cortex of MSC recipients. While there were no transplant-related changes in pE3-Aß plaque numbers, a reduction in the size of pE3-Aß plaques was observed in the hippocampus of transplant recipients. CONCLUSION: This is the first study to show reduction in pE3-Aß plaque size. pE3-Aß plaques have gained attention as potential key participants in AD due to their increased aggregation propensity, the possibility for the initial seeding event, resistance against degradation and neurotoxicity. These findings support the hypothesis that MSC-transplants may affect AD pathology via an immune-modulatory function that includes an effect on microglial cells.

Behavioral and emotional dysregulation trajectories marked by prefrontal-amygdala function in symptomatic youth.

BACKGROUND: Neuroimaging measures of behavioral and emotional dysregulation can yield biomarkers denoting developmental trajectories of psychiatric pathology in youth. We aimed to identify functional abnormalities in emotion regulation (ER) neural circuitry associated with different behavioral and emotional dysregulation trajectories using latent class growth analysis (LCGA) and neuroimaging. METHOD: A total of 61 youth (9-17 years) from the Longitudinal Assessment of Manic Symptoms study, and 24 healthy control youth, completed an emotional face n-back ER task during scanning. LCGA was performed on 12 biannual reports completed over 5 years of the Parent General Behavior Inventory 10-Item Mania Scale (PGBI-10M), a parental report of the child's difficulty regulating positive mood and energy. RESULTS: There were two latent classes of PGBI-10M trajectories: high and decreasing (HighD; n=22) and low and decreasing (LowD; n=39) course of behavioral and emotional dysregulation over the 12 time points. Task performance was >89% in all youth, but more accurate in healthy controls and LowD versus HighD (p<0.001). During ER, LowD had greater activity than HighD and healthy controls in the dorsolateral prefrontal cortex, a key ER region, and greater functional connectivity than HighD between the amygdala and ventrolateral prefrontal cortex (p's<0.001, corrected). CONCLUSIONS: Patterns of function in lateral prefrontal cortical-amygdala circuitry in youth denote the severity of the developmental trajectory of behavioral and emotional dysregulation over time, and may be biological targets to guide differential treatment and novel treatment development for different levels of behavioral and emotional dysregulation in youth.

Adenosine A(3) receptor-induced proliferation of primary human coronary smooth muscle cells involving the induction of early growth response genes.

In human coronary smooth muscle cells adenosine A(2B) receptors mediate the inhibition of platelet-derived growth factor (PDGF)-induced proliferation via induction of the transcription factor nuclear receptor subfamily 4, group A, member 1 (NR4A1). In the absence of PDGF, adenosine analogues increased proliferation. In the present study we characterised the adenosine receptor mediating the increase in proliferation of these cells and identified involved transcription factors. Cultured human coronary smooth muscle cells were treated with selective A(3) receptor ligands. Effects on proliferation were determined by counting cells and measuring changes in impedance. The induction of transcription factors was assessed by qPCR. The A(3) receptor agonist 2-chloro-IB-MECA (2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide) enhanced the number of human coronary smooth muscle cells with a half-maximal concentration of only 1 nM. 2-chloro-IB-MECA also increased the expression of the transcription factors early growth response protein (EGR)2 and EGR3, but not of EGR1, NR4A1, NR4A2 and NR4A3. The responses to 2-chloro-IB-MECA were blocked by two A(3) receptor antagonists, MRS1523 (3-propyl-6-ethyl-5[(ethylthio)carbonyl]-2-phenyl-4-propyl-3-pyridine-carboxylate; 10-300 µM) and VUF 5574 (N-(2-methoxyphenyl)-N'-[2-(3-pyridinyl)-4-quinazolinyl]-urea; 1-100 nM, as well as by the phospholipase C-inhibitor U73343 (0.2 µM). Small interfering RNA directed against EGR2 and EGR3 abolished the increases in proliferation induced by 2-chloro-IB-MECA. In summary, this is the first report demonstrating a coupling of smooth muscle adenosine A(3) receptors to increases in proliferation of human coronary smooth cells by the activation of phospholipase C and an induction of the transcriptions factors EGR2 and EGR3. The results facilitate the understanding of the role of adenosine A(3) receptors in the cardiovascular system.