Cancer incidence after an open cut coal mine fire.

Using population-level cancer diagnosis data, we compared cancer incidence in locations affected by smoke from a six week-long open cut coal mine fire in regional Victoria, Australia, up to seven years following the event. There was no detectable effect on cancer incidence overall. While several subgroups exhibited changes, these were more likely due to statistical chance rather than real effects. These findings may be limited by low statistical power and short duration of follow up. To confirm the influence of open cut coal mine fires on cancer incidence, further research and an extended follow-up duration are necessary.

Sociodemographic circumstances, health, and life experience shape posttraumatic distress trajectories among individuals exposed to smoke during a large-scale coal mine fire.

The 2014 Hazelwood coal mine fire in the Latrobe Valley, Australia, distributed toxic smoke into surrounding communities over 45 days. This study investigated risk and protective factors associated with four trajectories of posttraumatic distress (resilient, recovery, delayed-onset, chronic) among exposed adults. Participants (N = 709) completed surveys in 2016-2017 and 2019-2020 assessing mine fire-related particulate matter (PM2.5 ) exposure; sociodemographic, physical, and mental health variables; and exposure to other traumatic and recent stressful events. Mine fire-related posttraumatic distress was measured using the IES-R; trajectories were determined according to established clinical significance thresholds. Relative risk ratios (RRRs) were generated from multivariate multinomial regressions. The resilient trajectory was most common (77.0%). The chronic trajectory (8.5%) was associated with loneliness, RRR = 2.59, 95% CI [1.30, 5.16], and physical health diagnoses, RRR = 2.31, 95% CI [1.32, 4.02]. The delayed-onset trajectory (9.1%) was associated with multiple recent stressful events, RRR = 2.51, 95% CI [1.37, 4.59]; mental health diagnoses, RRR = 2.30, 95% CI [1.25, 4.24]; loneliness, RRR = 2.05, 95% CI [1.09, 3.88]; and male gender, RRR = 2.01, 95% CI [1.18, 3.44]. Socioeconomic advantage protected against chronic, RRR = 0.68, 95% CI [0.53, 0.86], and delayed-onset trajectory membership, RRR = 0.68, 95% CI [0.50, 0.94]; social support protected against chronic trajectory membership, RRR = 0.67, 95% CI [0.49, 0.92]. PM2.5 exposure did not determine trajectory. These findings enhance understanding of longer-term posttraumatic responses to large-scale smoke events and can inform mental health initiatives within at-risk communities.

An exploration of the trajectory of psychological distress associated with exposure to smoke during the 2014 Hazelwood coal mine fire.

Due to climate change, catastrophic events such as landscape fires are increasing in frequency and severity. However, relatively little is known about the longer-term mental health outcomes of such events. Follow-up was conducted of 709 adults exposed to smoke from the 2014 Hazelwood mine fire in Morwell, Victoria, Australia. Participants completed two surveys evaluating posttraumatic distress, measured using the Impact of Events Scale-Revised (IES-R), three and six years after the mine fire. Mixed-effects regression models were used to evaluate longitudinal changes in distress. IES-R total scores increased on average by 2.6 points (95%CI: 1.2 to 3.9 points) between the two survey rounds, with increases across all three posttraumatic distress symptom clusters, particularly intrusive symptoms. This increase in distress was evident across all levels of fine particulate matter (PM2.5) exposure to the mine fire smoke. Age was an effect modifier between mine fire PM2.5 exposure and posttraumatic distress, with younger adults impacted more by exposure to the mine fire. Greater exposure to PM2.5 from the mine fire was still associated with increased psychological distress some six years later, with the overall level of distress increasing between the two survey rounds. The follow-up survey coincided with the Black Summer bushfire season in south-eastern Australia and exposure to this new smoke event may have triggered distress sensitivities stemming from exposure to the earlier mine fire. Public health responses to disaster events should take into consideration prior exposures and vulnerable groups, particularly younger adults.

Long-term impacts of coal mine fire-emitted PM2.5 on hospitalisation: a longitudinal analysis of the Hazelwood Health Study.

BACKGROUND: Little is known about the long-term health impacts of exposures to landscape fire smoke. We aimed to evaluate the association between exposure to coal mine fire-related particulate matter 2.5 µm or less in diameter (PM2.5) and hospitalisation in the 5 years following the 6-week Hazelwood coal mine fire in Australia in 2014. METHODS: We surveyed 2725 residents (mean age: 58.3 years; 54.3% female) from an exposed and a comparison town. Individual PM2.5 exposures during the event were estimated using modelled PM2.5 concentrations related to the coal mine fire and self-reported location data. The individual exposure and survey data were linked with hospitalisation records between January 2009 and February 2019. Recurrent event survival analysis was used to evaluate relationships between PM2.5 exposure and hospitalisation following mine fire, adjusting for important covariates. RESULTS: Each 10-µg/m3 increase in mine fire-related PM2.5 was associated with a 9% increased hazard [hazard ratio (HR) = 1.09; 95% confidence interval (CI): 1.01, 1.17] of respiratory hospitalisation over the next 5 years, with stronger associations observed for females (HR = 1.16; 95% CI: 1.06, 1.27) than males (HR = 0.99; 95% CI: 0.89, 1.11). In particular, increased hazards were observed for hospitalisations for asthma (HR = 1.43; 95% CI: 1.19, 1.73) and chronic obstructive pulmonary disease (HR = 1.14; 95% CI: 1.02, 1.28). No such association was found for hospitalisations for cardiovascular diseases, mental illness, injuries, type 2 diabetes, renal diseases or neoplasms. CONCLUSIONS: A 6-week exposure to coal mine fire-related PM2.5 was associated with increased hazard of respiratory hospitalisations over the following 5 years, particularly for females.

Divergent receptor utilization is necessary for phrenic long-term facilitation over the course of motor neuron loss following CTB-SAP intrapleural injections.

Intrapleural injection of cholera toxin B conjugated to saporin (CTB-SAP) mimics respiratory motor neuron death and respiratory deficits observed in rat models of neuromuscular diseases. Seven-day CTB-SAP rats elicit enhanced phrenic long-term facilitation (pLTF) primarily through TrkB and PI3K/Akt-dependent mechanisms [i.e., Gs-pathway, which can be initiated by adenosine 2A (A2A) receptors in naïve rats], whereas 28-day CTB-SAP rats elicit moderate pLTF though BDNF- and MEK-/ERK-dependent mechanisms [i.e., Gq-pathway, which is typically initiated by serotonin (5-HT) receptors in naïve rats]. Here, we tested the hypothesis that pLTF following CTB-SAP is 1) A2A receptor-dependent at 7 days and 2) 5-HT receptor-dependent at 28 days. Adult Sprague-Dawley male rats were anesthetized, paralyzed, ventilated, and exposed to acute intermittent hypoxia (AIH; 3-, 5-min bouts of 10.5% O2) following bilateral, intrapleural injections at 7 days and 28 days of 1) CTB-SAP (25 µg) or 2) unconjugated CTB and SAP (control). Intrathecal C4 delivery included either the 1) A2A receptor antagonist (MSX-3; 10 µM; 12 µL) or 2) 5-HT receptor antagonist (methysergide; 20 mM; 15 µL). pLTF was abolished with A2A receptor inhibition in 7-day, not 28-day, CTB-SAP rats versus controls (P < 0.05), whereas pLTF was abolished following 5-HT receptor inhibition in 28-day, not 7-day, CTB-SAP rats versus controls (P < 0.05). In addition, 5-HT2A receptor expression was unchanged in CTB-SAP rats versus controls, whereas 5-HT2B receptor expression was decreased in CTB-SAP rats versus controls (P < 0.05). This study furthers our understanding of the contribution of differential receptor activation to pLTF and its implications for breathing following respiratory motor neuron death.NEW & NOTEWORTHY The current study investigates underlying receptor-dependent mechanisms contributing to phrenic long-term facilitation (pLTF) following CTB-SAP-induced respiratory motor neuron death at 7 days and 28 days. We found that A2A receptors are required for enhanced pLTF in 7-day CTB-SAP rats, whereas 5-HT receptors are required for moderate pLTF in 28-day CTB-SAP rats. Targeting these time-dependent mechanisms have implications for breathing maintenance over the course of many neuromuscular diseases.

Are e-cigarette use and vaping associated with increased respiratory symptoms and poorer lung function in a population exposed to smoke from a coal mine fire?

BACKGROUND AND OBJECTIVE: E-cigarette use has become increasingly prevalent, but there is some evidence demonstrating potential harms with frequent use. We aimed to identify the profiles of e-cigarette users from a regional community in Australia and investigate the associations of e-cigarettes with respiratory symptoms and lung function. METHODS: A total of 519 participants completed a cross-sectional study. Exposure to e-cigarettes was collected via a validated questionnaire. Respiratory symptoms were evaluated via a self-reported questionnaire and lung function measured with spirometry and forced oscillation technique (FOT). Linear and logistic regression models were fitted to investigate the associations between e-cigarettes and outcomes, while controlling for confounders such as tobacco smoking. RESULTS: Of the 519 participants, 46 (9%) reported e-cigarette use. Users tended to be younger (mean ± SD 45.2 ± 14.5 vs. 55.3 ± 16.0 years in non-users), concurrently using tobacco products (63% vs. 12% in non-users), have a mental health diagnosis (67% vs. 37% in non-users) and have self-reported asthma (63% vs. 42% in non-users). After controlling for known confounders, chest tightness (OR = 2.4, 95% CI 1.2-4.9, p = 0.02) was associated with e-cigarette use. Spirometry was not different after adjustment for confounding. However, FOT showed more negative reactance and a greater area under the reactance curve in e-cigarette users than non-users. CONCLUSION: E-cigarette use was associated with increased asthma symptoms and abnormal lung mechanics in our sample, supporting a potential health risk posed by these products. Vulnerable populations such as young adults and those with mental health conditions have higher usage, while there is high concurrent tobacco smoking.

A Prospective Randomized Clinical Trial in Total Hip Arthroplasty-Comparing Early Results Between the Direct Anterior Approach and the Posterior Approach.

BACKGROUND: We report a prospective randomized study comparing early clinical results between the direct anterior approach (DAA) and posterior approach (PA) in primary hip arthroplasty. METHODS: Surgeries were performed by 2 senior hip arthroplasty surgeons. Seventy-two patients with complete data were assessed preoperatively 2, 6, and 12 weeks postoperatively. The primary outcomes were the Western Ontario McMasters Arthritis Index and Oxford Hip Scores. Secondary outcome measures included the EuroQoL, 10-meter walk test, and clinical and radiographic parameters. RESULTS: Data analyses showed no difference between DAA (n = 35) and PA (n = 37) groups when comparing total scores for primary outcomes. No significant differences were observed for 10-meter walk test, EuroQoL, and radiographic analyses. Subgroup analysis for surgeon 1 identified that the DAA group had shorter acute hospital stay, less postoperative opiate requirements, and smaller wounds. However, this was offset by increased operative time, higher intraoperative blood loss, and weaker hip flexion at 2 and 6 weeks. Subgroup analysis of items on the Western Ontario McMasters Arthritis Index and Oxford Hip Score identified that hip flexion activity favored the DAA group up to 6 weeks postoperatively. There was an 83% incidence of lateral cutaneous nerve of thigh neuropraxia at the 12-week mark in the DAA group. No neuropraxias occurred in the PA group. One dislocation occurred in each group. A single patient from the DAA group required reoperation for leg-length discrepancy. CONCLUSION: DAA total hip arthroplasty (THA) has comparable results with PA THA. Choice of surgical approach for THA should be based on patient factors, surgeon preference, and experience.

Symptoms and lung function decline in a middle-aged cohort of males and females in Australia.

BACKGROUND: The European Community Respiratory Health Survey is a major international study designed to assess lung health in adults. This Australian follow-up investigated changes in symptoms between sexes and the roles of asthma, smoking, age, sex, height, and change in body mass index (ΔBMI) on lung function decline (LFD), which is a major risk factor for chronic obstructive pulmonary disease (COPD). METHODS: LFD was measured as the rate of decline over time in FEV1 (mL/year) (ΔFEV1) and FVC (ΔFVC) between 1993 and 2013. Multiple linear regression was used to estimate associations between risk factors and LFD, separately for males and females. Multiple logistic regression was used to assess sex differences and changes in respiratory symptoms over time. RESULTS: In Melbourne, 318 subjects (53.8% females) participated. The prevalence of most respiratory symptoms had either remained relatively stable over 20 years or decreased (significantly so for wheeze). The exception was shortness of breath after activity, which had increased. Among the 262 subjects who completed spirometry, current smoking declined from 20.2% to 7.3%. Overall mean (± standard deviation) FEV1 declined by 23.1 (±17.1) and FVC by 22.9 (±20.2) mL/year. Predictors of ΔFEV1 in males were age, maternal smoking, and baseline FEV1; and in females they were age, ΔBMI, baseline FEV1, and pack-years in current smokers. Decline in FVC was predicted by baseline FVC, age, and ΔBMI in both sexes; however, baseline FVC predicted steeper decline in females than males. CONCLUSION: Most respiratory symptoms remained stable or decreased over time in both sexes. Age, baseline lung function, and change in BMI were associated with the rate of decline in both sexes. However, obesity and personal smoking appear to put females at higher risk of LFD than males. Health promotion campaigns should particularly target females to prevent COPD.

Evidence that proteasome-dependent degradation of the retinoblastoma protein in cells lacking A-type lamins occurs independently of gankyrin and MDM2.

BACKGROUND: A-type lamins, predominantly lamins A and C, are nuclear intermediate filaments believed to act as scaffolds for assembly of transcription factors. Lamin A/C is necessary for the retinoblastoma protein (pRB) stabilization through unknown mechanism(s). Two oncoproteins, gankyrin and MDM2, are known to promote pRB degradation in other contexts. Consequently, we tested the hypothesis that gankyrin and/or MDM2 are required for enhanced pRB degradation in Lmna-/- fibroblasts. Principal Findings. To determine if gankyrin promotes pRB destabilization in the absence of lamin A/C, we first analyzed its protein levels in Lmna-/- fibroblasts. Both gankyrin mRNA levels and protein levels are increased in these cells, leading us to further investigate its role in pRB degradation. Consistent with prior reports, overexpression of gankyrin in Lmna+/+ cells destabilizes pRB. This decrease is functionally significant, since gankyrin overexpressing cells are resistant to p16(ink4a)-mediated cell cycle arrest. These findings suggest that lamin A-mediated degradation of pRB would be gankyrin-dependent. However, effective RNAi-enforced reduction of gankyrin expression in Lmna-/- cells was insufficient to restore pRB stability. To test the importance of MDM2, we disrupted the MDM2-pRB interaction by transfecting Lmna-/- cells with p14(arf). p14(arf) expression was also insufficient to stabilize pRB or confer cell cycle arrest, suggesting that MDM2 also does not mediate pRB degradation in Lmna-/- cells. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that pRB degradation in Lmna-/- cells occurs by gankyrin and MDM2-independent mechanisms, leading us to propose the existence of a third proteasome-dependent pathway for pRB degradation. Two findings from this study also increase the likelihood that lamin A/C functions as a tumor suppressor. First, protein levels of the oncoprotein gankyrin are elevated in Lmna-/- fibroblasts. Second, Lmna-/- cells are refractory to p14(arf)-mediated cell cycle arrest, as was previously shown with p16(ink4a). Potential roles of lamin A/C in the suppression of tumorigenesis are discussed.

HuD distribution changes in response to heat shock but not neurotrophic stimulation.

Cellular stress leads to a change in distribution of RNA-binding proteins. HuR, a member of the ELAV/Hu family of RNA-binding proteins, is nuclear in distribution and following heat shock is found in large cytoplasmic stress granules where translation is inhibited. HuD, another ELAV/Hu RNA-binding protein, stabilizes the GAP-43 mRNA in response to nerve growth factor (NGF) stimulation in PC12 cells. We were interested in determining the nuclear distribution of HuD and if neurotrophic stimulation induced changes in the distribution of HuD. In PC12 cells, we found, as expected, that HuR translocates from the nucleus to the cytoplasm in response to heat shock. In response to heat shock, HuD forms large cytoplasmic stress granules, consistent with a role for HuD in the cessation of translation. In unstimulated cells, HuD is distributed in small granules in the cytoplasm and is consistently present at low levels in the nucleus. Stimulation of PC12 cells with NGF induces neuronal differentiation including outgrowth of neurites and increased levels of GAP-43 protein, whereas HuD remains localized in small cytoplasm granules and is still present in the nucleus. These results suggest that, following neurotrophic stimulation, the lack of changes in HuD distribution are due to continued steady state of HuD nuclear shuttling in PC12 cells, or that HuD is not normally shuttled from the nucleus in response to NGF.

GAP-43 mRNA in growth cones is associated with HuD and ribosomes.

The neuron-specific ELAV/Hu family member, HuD, interacts with and stabilizes GAP-43 mRNA in developing neurons, and leads to increased levels of GAP-43 protein. As GAP-43 protein is enriched in growth cones, it is of interest to determine if HuD and GAP-43 mRNA are associated in developing growth cones. HuD granules in growth cones are found in the central domain that is rich in microtubules and ribosomes, in the peripheral domain with its actin network, and in filopodia. This distribution of HuD granules in growth cones is dependent on actin filaments but not on microtubules. GAP-43 mRNA is localized in granules found in both the central and peripheral domains, but not in filopodia. Ribosomes were extensively colocalized with HuD and GAP-43 mRNA granules in the central domain, consistent with a role in the control of GAP-43 mRNA stability in the growth cone. Together, these results demonstrate that many of the components necessary for GAP-43 mRNA translation/stabilization are present within growth cones.

Analytic methods for comparing two dichotomous screening or diagnostic tests applied to two populations of differing disease prevalence when individuals negative on both tests are unverified.

Two dichotomous screening tests may be compared by applying both tests to all members of a sampled population. For individuals with a positive result on either test the disease status may be verified by a reference standard, but for individuals negative on both tests the disease status may be unverified because the probability of disease is so low that further investigation is costly, unacceptable and perhaps unethical. If the tests have been applied to samples from two populations which have different disease prevalences then unbiased estimates of the true positive and false positive rates of each test, the prevalences in the two populations, and two parameters representing dependence between the two tests can be estimated using maximum likelihood methods. The methods are based on the assumption that the sensitivities and specificities of the two tests, and the dependencies between the tests, are independent of prevalence. A test of goodness of fit provides a test of this.