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Juan Mundisugih,1,2 Caroline X Gao,1,3 Jillian F Ikin,1 Michael J Abramson,1 David Brown,1 Sinjini Biswas,1,2 Elizabeth M Dewar,2,4 Danny Liew,1 Dion Stub1,2,4 1School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia; 2Department of Cardiology, Alfred Health, Melbourne, VIC, Australia; 3Centre for Youth Mental Health (Orygen), University of Melbourne, Melbourne, VIC, Australia; 4Baker Heart and Diabetes Institute, Melbourne, VIC, AustraliaCorrespondence: Jillian F Ikin, Tel +61 3 9903 0308, Email jill.blackman@monash.eduBackground and Aims: Mega-wild fires are exposing large communities to weeks or months of high concentration smoke-related fine particulate air pollution (PM). However, little research has examined the long-term vascular responses from exposure to PM of this concentration and duration. We investigated whether level of exposure to 6 weeks of PM from the 2014 Hazelwood coal mine fire was associated with abnormal vascular responses approximately four years later.Methods: A cross-sectional analysis was undertaken of 387 participants (225 exposed, 162 unexposed) aged 55– 89 years, 3.5– 4 years after the mine fire. The primary outcome was flow-mediated dilatation (FMD), with time to reach peak diameter as the secondary outcome. Other secondary markers included high-sensitivity C-reactive protein (hsCRP) and ischaemic Electrocardiogram (ECG) changes.Results: There was no evidence of a difference in FMD between participants with high, medium, low or no mine-fire related PM2.5 exposure (4.09% vs 4.06% vs 4.02% vs 3.98%, respectively, p=0.99). Likewise, there was no difference in hsCRP or ischaemic ECG changes. In contrast, there was evidence of a difference in time to peak diameter (p=0.002) with more unexposed participants reaching peak diameter within 30 seconds (36%) compared to those who had high, medium, or low exposure (23%, 22%, 13%, respectively). Multivariate ordinal logistic regression analysis suggested that township, Morwell (exposed) vs Sale (unexposed), but not level of PM2.5 exposure, was associated with delayed time to peak diameter (OR 2.71; 95% CI 1.56, 4.69). Smokers also had delayed time to peak diameter.Conclusion: There was no association between level of exposure to PM2.5 from the 6-week Hazelwood coal mine fire smoke event and reduced FMD, elevated hsCRP or ischaemic ECG four years later. Evidence of delayed time to peak diameter observed in adults from the exposed town, compared to an unexposed town, requires further investigation.Keywords: vascular responses, flow mediated dilatation, time to peak diameter, particulate matter, epidemiology, air pollution

Hai-Sheng You,1,* Chun-Xia Gao,1,* Hai-Bin Wang,2 Sai-Sai Luo,1 Si-Ying Chen,1 Ya-Lin Dong,1 Jun Lyu,3 Tao Tian4 1Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Hangzhou Cognitive N&T. Co., Ltd, Hangzhou, Zhengjiang, People’s Republic of China; 3Clinical Research Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 4Department of Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tao TianDepartment of Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 West Yanta Road, Xi’an, Shaanxi 710061, People’s Republic of ChinaTel +86-13572206784Fax +86-29-85324086Email tiantao0607@163.comJun LyuClinical Research Center, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 West Yanta Road, Xi’an, Shaanxi 710061, People’s Republic of ChinaTel +86 29 8532 3614Fax +86 29 8532 3473Email lujun2006@xjtu.edu.cnObjective: The disease complexity of metastatic non-small-cell lung cancer (mNSCLC) makes it difficult for physicians to make clinical decisions efficiently and accurately. The Watson for Oncology (WFO) system of artificial intelligence might help physicians by providing fast and precise treatment regimens. This study measured the concordance of the medical treatment regimens of the WFO system and actual clinical regimens, with the aim of determining the suitability of WFO recommendations for Chinese patients with mNSCLC.Methods: Retrospective data of mNSCLC patients were input to the WFO, which generated a treatment regimen (WFO regimen). The actual regimen was made by physicians in a medical team for patients (medical-team regimen). The factors influencing the consistency of the two treatment options were analyzed by univariate and multivariate analyses.Results: The concordance rate was 85.16% between the WFO and medical-team regimens for mNSCLC patients. Logistic regression showed that the concordance differed significantly for various pathological types and gene mutations in two treatment regimens. Patients with adenocarcinoma had a lower rate of “recommended” regimen than those with squamous cell carcinoma. There was a statistically significant difference in EGFR-mutant patients for “not recommended” regimens with inconsistency rate of 18.75%. In conclusion, the WFO regimen has 85.16% consistency rate with medical-team regimen in our treatment center. The different pathological type and different gene mutation markedly influenced the agreement rate of the two treatment regimens.Conclusion: WFO recommendations have high applicability to mNSCLC patients in our hospital. This study demonstrates that the valuable WFO system may assist the doctors better to determine the accurate and effective treatment regimens for mNSCLC patients in the Chinese medical setting.Keywords: metastatic non-small-cell lung cancer, Watson for Oncology, concordance, artificial intelligence, treatment recommendations

Li Cheng,1 Doris Yin-ping Leung,1 Janet Wing-hung Sit,1 Xiao-mei Li,2 Yu-ning Wu,3 Miao-yan Yang,4 Cui-xia Gao,5 Rong Hui6 1The Nethersole School of Nursing, Faculty of Medicine, The Chinese University of Hong Kong, Ma Liu Shui, Shatin, New Territories, Hong Kong; 2The Department of Nursing, Faculty of Medicine, The Xi’an Jiaotong University, 3The Department of Endocrinology, The Ninth Affiliated Hospital of Xi’an Jiaotong University, 4The Department of Endocrinology, The Second Affiliated Hospital of Xi’an Jiaotong University, 5The Department of Endocrinology, The First Affiliated Hospital of Xi’an Jiaotong University, 6The Department of Endocrinology, Shaanxi Provincial People’s Hospital, Xi’an, People’s Republic of China Background: The study was conducted to investigate the diet barriers perceived by patients with poorly controlled type 2 diabetes and examine the associations between diet barriers and sociodemographic characteristics, medical condition, and patient-centered variables. Methods: Secondary subgroup analyses were conducted based on the responses of 246 adults with poorly controlled type 2 diabetes from a multicenter, cross-sectional study. Diet barriers were captured by the Diet Barriers subscale of the Personal Diabetes Questionnaire. Participants also completed validated measures of diet knowledge, empowerment level, and appraisal of diabetes. Multiple regression techniques were used for model building, with a hierarchical block design to determine the separate contribution of sociodemographic characteristics, medical condition, and patient-centered variables to diet barriers. Results: Diet barriers were moderately evident (2.23±0.86) among Chinese patients with poorly controlled type 2 diabetes. The feeling of deprivation as a result of complying with a diet was the most recognized diet barrier (3.24±1.98), followed by “eating away from home” (2.79±1.82). Significantly higher levels of diet barriers were observed among those with lower levels of diet knowledge (β=-0.282, P

Background and Objective: The 2014 Hazelwood coal mine fire exposed residents in nearby Morwell to high concentrations of particulate matter <2.5 µm (PM 2.5 ) for approximately 6 weeks. This analysis aimed to evaluate the long-term impact on respiratory health., Methods: Adults from Morwell and the unexposed town of Sale completed validated respiratory questionnaires and performed spirometry, gas transfer and oscillometry 3.5-4 years (round 1) and 7.3-7.8 years (round 2) after the fire. Individual PM 2.5 exposure levels were estimated using chemical transport models mapped onto participant-reported time-location data. Mixed-effects regression models were fitted to analyse associations between PM 2.5 exposure and outcomes, controlling for key confounders., Results: From 519 (346 exposed) round 1 participants, 329 (217 exposed) participated in round 2. Spirometry and gas transfer in round 2 were mostly lower compared with round 1, excepting forced vital capacity (FVC) (increased) and forced expiratory volume in 1 second (minimal change). The effect of mine fire-related PM 2.5 exposure changed from a negative effect in round 1 to no effect in round 2 for both pre-bronchodilator (p=0.005) and post-bronchodilator FVC (p=0.032). PM 2.5 was not associated with gas transfer in either round. For post-bronchodilator reactance and area under the curve, a negative impact of PM 2.5 in round 1 showed signs of recovery in round 2 (both p<0.001)., Conclusion: In this novel study evaluating long-term respiratory outcomes after medium-duration high concentration PM 2.5 exposure, the attenuated associations between exposure and respiratory function may indicate some recovery in lung function. With increased frequency and severity of landscape fires observed globally, these results inform public health policies and planning., Competing Interests: Competing interests: MJA declares an unrelated consultancy with Sanofi, investigator initiated grants from Pfizer, Boehringer-Ingelheim, Sanofi and GlaxoSmithKline, a speakers fee from GSK, honorarium from The Limbic and honorary membership of the Data Safety Monitoring Board of the Woolcock Institute of Medical Research. The other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: The Hazelwood Health Study was set up to study long-term health effects of a mine fire that blanketed residents of the Latrobe Valley with smoke for 45 days in 2014. The Respiratory Stream specifically assessed the impact of fine particulate matter <2.5 μm diameter (PM 2.5 ) exposure from mine fire smoke on lung health. The multiple breath nitrogen washout (MBW) test assesses ventilation heterogeneity, which may detect sub-clinical airways dysfunction not identified using standard tests such as spirometry. This analysis assessed the association of PM 2.5 exposure with measures of ventilation heterogeneity., Methods: Exposed (Morwell) and unexposed (Sale) participants were recruited 3.5-4 years after the fire from those who had participated in an Adult Survey. MBW was performed to measure lung clearance index (LCI), functional residual capacity (FRC), acinar (Sacin) and conductive (Scond) ventilation heterogeneity. PM 2.5 exposure was estimated with emission and chemical transport models. Multivariable linear regression models were fitted controlling for confounders., Results: We recruited 519 participants. MBW tests were conducted on 504 participants with 479 acceptable test results (40% male; 313 exposed, 166 unexposed). Exposure to mine fire-related PM 2.5 was associated with increasing Scond (β = 1.57/kL, 95%CI: 0.20-2.95, p = 0.025), which was comparable to the estimated effect on Scond of 4.7 years of aging. No other MBW outcomes were statistically different., Conclusion: Increasing exposure to PM 2.5 was associated with increased ventilation heterogeneity in the conductive region of the lungs 4 years after the event., (© 2024 The Author(s). Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Objective: As highlighted in Australia's Productivity Commission Inquiry into mental health, subgroups of individuals are failing to have their needs met, or are 'falling through the cracks' in the current system - a phenomenon increasingly referred to as the 'missing middle'. A barrier to devising solutions is that the term 'missing middle' is not clearly defined. Using the Delphi method, we aimed to define the term and explore acceptability., Method: Three expert groups were recruited: carers and young people with a lived experience of mental ill-health; clinicians and service providers; researchers, policymakers and commissioners of mental health services. Using a three-stage Delphi process, we elicited definitions, refined and developed a consensus definition., Results: Ten subthemes describing the 'missing middle' were identified, with four endorsed across all expert groups from the outset: service gap, inflexibility, inadequate service quality and duration, and social disadvantage. Additional subthemes were later endorsed. Feedback was sought on a consensus-driven definition that encompassed the original four endorsed subthemes. Findings supported a shift to a systemic focus - framing the 'missing middle' as a care gap., Conclusions: A consensus definition was developed, repositioning the term to a systems lens, describing a 'missing middle service gap'. The definition represents the 'missing middle' as a term to describe a gap in care where existing mental health services are not meeting the needs of individuals in a meaningful way. Research was carried out in relation to youth mental health in Australia and the definition may need to be adapted for other contexts., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: In 2014, the Hazelwood coalmine fire in regional Victoria, Australia shrouded nearby communities in smoke for six weeks. Prior investigations identified substantial adverse effects, including increases in the use of health services. In this study, we examined the effects on hospital and ambulance use in the eight years following the fire., Methods: Using Victorian hospital (Jan 2009-Jun 2022) and ambulance (Jan 2013-Dec 2021) data, we conducted an interrupted time series of changes to the rate of hospital admissions, emergency presentations, and ambulance attendances. A categorical exposure model compared two locations, most-exposed Morwell and less-exposed Latrobe Valley, to the rest of regional Victoria. A continuous exposure model used spatial estimates of fire-related PM 2.5 . Analyses were stratified by sex, age group (<65/65+ years), and condition (cardiovascular, respiratory, mental health, injury)., Results: There were small but significant increases in overall hospital admissions and emergency presentations across all analyses, but little evidence of change in overall ambulance attendances. Effects varied considerably by condition, with the biggest relative increases observed among hospital admissions for mental health conditions and injuries. While cardiovascular-related hospital admissions and emergency presentations increased post-fire, ambulance attendances decreased., Conclusions: Our findings suggest the Hazelwood coalmine fire likely increased hospital usage. However, it is unclear whether this was due to the direct effects of smoke exposure on health, or the disruptive socioeconomic and behavioural impacts of an environmental disaster that affected how communities engaged with various health services., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Michael J Abramson reports financial support was provided by Pfizer Inc. Michael J Abramson reports financial support was provided by Boehringer Ingelheim Corp USA. Michael J Abramson reports financial support was provided by Sanofi. Michael J Abramson reports financial support was provided by GlaxoSmithKline Inc. Rongbin Xu reports financial support was provided by VicHealth. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In Australia, the first nationwide COVID-19 lockdown occurred in March 2020 bringing challenges for early intervention psychosis (EIP) services. Limited evidence exists on the impacts of the pandemic on treatment outcomes among EIP clients., Methods: This prospective cohort study analysed routine data from 15 headspace Early Psychosis centres in Australia. Participants were 12 to 25 years, meeting criteria for First Episode Psychosis (FEP) or Ultra High Risk of psychosis (UHR) comparing those who commenced treatment 'pre-COVID-19' (between 16th August 2018 and 15th August 2019), and 'during-COVID-19' (between 1st March 2020 and 15th September 2020). Clinical symptoms at treatment commencement were assessed using the Brief Psychiatric Rating Scale (BPRS) and the Kessler Psychological Distress Scale (K10). with outcomes after 6 months compared between cohorts using linear mixed-effects regression, controlling for confounders., Results: Of 1246 young people analysed (653 FEP, 596 UHR), significant improvements were observed with treatment in both groups (5 to 13-point reduction in BPRS score per 6-months treatment). Treatment effectiveness reduced during-COVID-19 for psychosis symptoms, with the FEP BPRS treatment effect lower by 4.3 points (95%CI: 0.5, 8.1). UHR clients had lower BPRS negative symptoms during-COVID-19 (p = 0.020). Service contacts increased during-COVID-19, with increased telehealth services (p < 0.001)., Conclusions: Early intervention remained effective for FEP and UHR, despite the pandemic and transition of EIP services to virtual service delivery. Reduced treatment efficacy in FEP psychosis symptoms may indicate potential limitations of telehealth. Further research to examine longer term clinical and functional outcomes due to the pandemic is required., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest MJA holds investigator-initiated grants from Pfizer, Boehringer-Ingelheim, GSK and Sanofi for unrelated research. He has undertaken an unrelated consultancy for Sanofi. He has also received a speaker’s fee from GSK. All other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: Young people with first-episode psychosis (FEP) or at ultra-high risk (UHR) of psychosis often have lower vocational engagement than their peers. This study examines the effect of treatment in early intervention for psychosis services in Australia on engagement in education and employment., Methods: This is a naturalistic sample of young people aged 12-25 with FEP ( n = 1574) and UHR ( n = 1515), accessing treatment in the headspace Early Psychosis (hEP) programme. Engagement in education and employment was assessed at baseline and every 90 days in treatment. Mixed effects logistic regression were used to analyse changes over time., Results: On entering the hEP programme, approximately 49% of the young people with FEP and 28% of the young people at UHR status identified as Not in Education, Employment or Training (NEET). The odds of being NEET were reduced by 27% (95% confidence interval = [14, 39]) for every 6 months treatment for the FEP group, but no change in NEET status was observed in the UHR group. In both groups, absence from daily activities was significantly reduced during time in treatment., Conclusion: While there are methodological challenges analysing real-world non-control group cohort data, the findings indicate positive effects of the hEP programme on vocational and daily activity engagement for young people with FEP and at UHR status. A large proportion of the young people still identified as NEET after receiving treatment services, suggesting further refinement to ensure targeted and consistent vocational support throughout care., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aims: Most lifetime mental health disorders begin by age 25 years, and the prevalence among young people has been increasing over recent years. We sought to understand what impact, if any, social determinants have had on this increase through the analysis of an Australian longitudinal dataset (with data from 2007 to 2021)., Methods: The analysis focused on five social determinants: loneliness and lack of social support, family relationships, participation in education and employment, receipt of government benefits and relative socio-economic status. We analysed cross-sectional changes in self-reported psychological distress between 2007 and 2021 (using the Kessler-10 item; K10 scores) and examined the effects of these five social determinants on psychological distress using weighted linear regression models., Results: We identified a significant increase in psychological distress among Australians from 2007 to 2021, with the sharpest rise among those aged 15 to 25 years, who saw more than doubling in the percentage of high and very high K10. This period also saw an increase in the prevalence of social determinants such as loneliness and lack of social support, as well as poor family relationships, particularly in 2021 post COVID-19 pandemic. Regression models suggest loneliness and lack of social support had the most pronounced and increasing impact on psychological distress, followed by poor family relationships., Discussion: The observed significant and steady increases in psychological distress and related social determinant factors, particularly loneliness and lack of social support among young people, highlight the urgent need for comprehensive actions. Coordinated research and community-based initiatives are needed to deliver intrapersonal, interpersonal and socially-focused interventions with a holistic approach to support psychosocial wellbeing. Policymakers must adopt a comprehensive shift in political commitment and a whole-of-government approach to address these challenges., Competing Interests: Conflict of interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: rygen is funded by the Australian Government Department of Health and Aged Care to provide technical advice and policy direction on a number of youth mental health topics, including social determinants. This is relevant for DB, RM and VB.

Aims: The specific and multifaceted service needs of young people have driven the development of youth-specific integrated primary mental healthcare models, such as the internationally pioneering headspace services in Australia. Although these services were designed for early intervention, they often need to cater for young people with severe conditions and complex needs, creating challenges in service planning and resource allocation. There is, however, a lack of understanding and consensus on the definition of complexity in such clinical settings., Methods: This retrospective study involved analysis of headspace 's clinical minimum data set from young people accessing services in Australia between 1 July 2018 and 30 June 2019. Based on consultations with experts, complexity factors were mapped from a range of demographic information, symptom severity, diagnoses, illness stage, primary presenting issues and service engagement patterns. Consensus clustering was used to identify complexity subgroups based on identified factors. Multinomial logistic regression was then used to evaluate whether these complexity subgroups were associated with other risk factors., Results: A total of 81,622 episodes of care from 76,021 young people across 113 services were analysed. Around 20% of young people clustered into a 'high complexity' group, presenting with a variety of complexity factors, including severe disorders, a trauma history and psychosocial impairments. Two moderate complexity groups were identified representing 'distress complexity' and 'psychosocial complexity' (about 20% each). Compared with the 'distress complexity' group, young people in the 'psychosocial complexity' group presented with a higher proportion of education, employment and housing issues in addition to psychological distress, and had lower levels of service engagement. The distribution of complexity profiles also varied across different headspace services., Conclusions: The proposed data-driven complexity model offers valuable insights for clinical planning and resource allocation. The identified groups highlight the importance of adopting a holistic and multidisciplinary approach to address the diverse factors contributing to clinical complexity. The large number of young people presenting with moderate-to-high complexity to headspace early intervention services emphasises the need for systemic change in youth mental healthcare to ensure the availability of appropriate and timely support for all young people.

Arsenic contamination in environmental water sources poses a significant threat to human health, necessitating the development of sensitive and accessible detection methods. This study presents a multidimensional optimization of a bacterial biosensor for the susceptible and deoxyviolacein (DV)-based visual detection of arsenic. The research involved screening six different arsenic resistance (ars) operons and optimizing the genetic circuit to minimize background noise. Introducing an arsenic-specific transport channel enhanced the sensor's sensitivity to 1 nM with a quantitative range from 0.036 to 1.171 μM. The pigment-based biosensor offers a simple colorimetric approach for arsenic detection without complex instrumentation. The preferred biosensor demonstrated characteristics of anti-chelating agent interference, consistently quantified As(III) concentrations ranging from 0.036 to 1.171 μM covering the World Health Organization (WHO) drinking water limit. Innovatively, it effectively detects arsenic in seawater within a linear regression range of 0.071 to 1.125 μM. The biosensor's selectivity for arsenic was confirmed, with minimal cross-response to group 15 metals. Our naked-eye biosensor offers a novel approach for the rapid, on-site detection of arsenic in various water sources. Its simplicity, cost-effectiveness, and versatility make it a valuable tool for environmental monitoring and public health initiatives., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Melatonin (MLT) is a circadian hormone that reportedly influences the development and cyclic growth of secondary hair follicles; however, the mechanism of regulation remains unknown. Here, we systematically investigated the role of MLT in hair regeneration using a hair depilation mouse model. We found that MLT supplementation significantly promoted hair regeneration in the hair depilation mouse model, whereas supplementation of MLT receptor antagonist luzindole significantly suppressed hair regeneration. By analysing gene expression dynamics between the MLT group and luzindole-treated groups, we revealed that MLT supplementation significantly up-regulated Wnt/β-catenin signalling pathway-related genes. In-depth analysis of the expression of key molecules in the Wnt/β-catenin signalling pathway revealed that MLT up-regulated the Wnt/β-catenin signalling pathway in dermal papillae (DP), whereas these effects were facilitated through mediating Wnt ligand expression levels in the hair follicle stem cells (HFSCs). Using a DP-HFSCs co-culture system, we verified that MLT activated Wnt/β-catenin signalling in DPs when co-cultured with HFSCs, whereas supplementation of DP cells with MLT alone failed to activate Wnt/β-catenin signalling. In summary, our work identified a critical role for MLT in promoting hair regeneration and will have potential implications for future hair loss treatment in humans., (© 2024 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

During a survey of the diversity of lignicolous fungi in Yunnan Province, China, we collected and identified five microfungi species from dead woody litters of Castanopsis trees in terrestrial habitats. Through both morphological comparisons and phylogenetic analyses of multi-gene sequences, we identified two taxa as new species and three collections as new host records within Pleosporales. Pseudolophiostomalincangense sp. nov. is introduced as a sexual morph in Lophiostomataceae, Pleopunctumbaoshanense sp. nov. is introduced as a hyphomycetous fungi in Phaeoseptaceae, and Paraphomaaquatica as a first report of sexual morph in Paraphoma . In addition, Occultibambusakunmingensis and Pleopunctummegalosporum were isolated for the first time from the dead twigs of Castanopsisdelavayi and C.calathiformis , respectively. Comprehensive morphological descriptions, illustrations, and phylogenetic analysis results are provided for the above-mentioned species., Competing Interests: The authors have declared that no competing interests exist., (Guang-Cong Ren, Saowaluck Tibpromma, Kai-Xuan Dong, Chen-Xi Gao, Chao-Shan Zhang, Samantha C. Karunarathna, Abdallah M. Elgorban, Heng Gui.)

Background and Aims: Since the onset of the COVID-19 pandemic, a significant rise in mental ill health has been observed globally in young people, particularly those in their final years of secondary school. Students' negative experiences coincide with a critical transitional period which can disrupt milestones in social and educational development. This study aimed to use innovative population-level data to map the impact of the pandemic on students entering higher education., Methods: Pre-pandemic (2019/2020) and pandemic (2020/2021) tertiary education application data were obtained from the Victorian Tertiary Admissions Centre. Prevalence of applications for special consideration related to mental ill health were compared between cohorts across various geographical areas and applicant demographic subgroups. Relative risk regression models were used to understand the role of different risk factors., Results: Rates of mental health-related special consideration applications increased by 38% among all applications (pre-pandemic: 7.8%, n = 56 916; pandemic: 10.8%, n = 58 260). Highest increases were observed among students in areas with both extended and close-quarter lockdown experiences, and areas impacted by 2019/2020 black summer bushfires. The increases were higher among Year 12 students and students with other special consideration needs (e.g., physical condition, learning disability). Slightly higher increases were observed in areas with higher socio-economic status, which may potentially be related to inequality in mental health service access., Conclusion: As consequences of mental health difficulties and academic disruption in youth can be long lasting, it is critical to establish a mental health support framework both in and outside of higher education to facilitate young people's recovery from the pandemic., (© 2024 The Author(s). Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Fermentative production of natural colorants using microbial strains has emerged as a cost-effective and sustainable alternative to chemical synthesis. Visual pigments are used as signal outputs in colorimetric bacterial biosensors, a promising method for monitoring environmental pollutants. In this study, we engineered four self-sufficient indigo-forming enzymes, including HbpAv, bFMO, cFMO, and rFPMO, in a model bacterium E. coli . TrxA-bFMO was chosen for its strong ability to produce indigo under T7 lac and mer promoters' regulation. The choice of bacterial hosts, the supplementation of substrate l-tryptophan, and ventilation were crucial factors affecting indigo production. The indigo reporter validated the biosensors for Hg(II), Pb(II), As(III), and Cd(II). The biosensors reported Hg(II) as low as 14.1 nM, Pb(II) as low as 1.5 nM, and As(III) as low as 4.5 nM but increased to 25 μM for Cd(II). The detection ranges for Hg(II), Pb(II), As(III), and Cd(II) were quantified from 14.1 to 225 nM, 1.5 to 24.4 nM, 4.5 to 73.2 nM, and 25 to 200 μM, respectively. The sensitivity, responsive concentration range, and selectivity are comparable to β-galactosidase and luciferase reporter enzymes. This study suggests that engineered enzymes for indigo production have great potential for green chemical synthesis. Additionally, heterologous biosynthesis of indigo production can lead to the development of novel, low-cost, and mini-equipment bacterial biosensors with zero background noise for visual monitoring of pollutant heavy metals., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: In randomized clinical trials, treatment effects may vary, and this possibility is referred to as heterogeneity of treatment effect (HTE). One way to quantify HTE is to partition participants into subgroups based on individual's risk of experiencing an outcome, then measuring treatment effect by subgroup. Given the limited availability of externally validated outcome risk prediction models, internal models (created using the same dataset in which heterogeneity of treatment analyses also will be performed) are commonly developed for subgroup identification. We aim to compare different methods for generating internally developed outcome risk prediction models for subject partitioning in HTE analysis., Methods: Three approaches were selected for generating subgroups for the 2,441 participants from the United States enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) randomized controlled trial. An extant proportional hazards-based outcomes predictive risk model developed on the overall ASPREE cohort of 19,114 participants was identified and was used to partition United States' participants by risk of experiencing a composite outcome of death, dementia, or persistent physical disability. Next, two supervised non-parametric machine learning outcome classifiers, decision trees and random forests, were used to develop multivariable risk prediction models and partition participants into subgroups with varied risks of experiencing the composite outcome. Then, we assessed how the partitioning from the proportional hazard model compared to those generated by the machine learning models in an HTE analysis of the 5-year absolute risk reduction (ARR) and hazard ratio for aspirin vs. placebo in each subgroup. Cochran's Q test was used to detect if ARR varied significantly by subgroup., Results: The proportional hazard model was used to generate 5 subgroups using the quintiles of the estimated risk scores; the decision tree model was used to generate 6 subgroups (6 automatically determined tree leaves); and the random forest model was used to generate 5 subgroups using the quintiles of the prediction probability as risk scores. Using the semi-parametric proportional hazards model, the ARR at 5 years was 15.1% (95% CI 4.0-26.3%) for participants with the highest 20% of predicted risk. Using the random forest model, the ARR at 5 years was 13.7% (95% CI 3.1-24.4%) for participants with the highest 20% of predicted risk. The highest outcome risk group in the decision tree model also exhibited a risk reduction, but the confidence interval was wider (5-year ARR = 17.0%, 95% CI= -5.4-39.4%). Cochran's Q test indicated ARR varied significantly only by subgroups created using the proportional hazards model. The hazard ratio for aspirin vs. placebo therapy did not significantly vary by subgroup in any of the models. The highest risk groups for the proportional hazards model and random forest model contained 230 participants each, while the highest risk group in the decision tree model contained 41 participants., Conclusions: The choice of technique for internally developed models for outcome risk subgroups influences HTE analyses. The rationale for the use of a particular subgroup determination model in HTE analyses needs to be explicitly defined based on desired levels of explainability (with features importance), uncertainty of prediction, chances of overfitting, and assumptions regarding the underlying data structure. Replication of these analyses using data from other mid-size clinical trials may help to establish guidance for selecting an outcomes risk prediction modelling technique for HTE analyses., (© 2024. The Author(s).)

In 2014, a fire at an open cut coalmine in regional Victoria, Australia burned for 6 weeks. Residents of the nearby town of Morwell were exposed to smoke, which included high levels of fine particulate matter (PM 2.5 ). We investigated whether the long-term effects of PM 2.5 on respiratory health were moderated by diet quality. A cross-sectional analysis was conducted of data collected 8.5 years after the mine fire from 282 residents of Morwell and 166 residents from the nearby unexposed town of Sale. Primary outcomes were respiratory symptoms. Exposure was coalmine fire-related PM 2.5 and diet quality was assessed as Australian Recommended Food Score (ARFS) derived using the Australian Eating Survey (AES). The moderating effect of diet quality on respiratory outcomes associated with PM 2.5 was assessed using logistic regression models, adjusting for potential confounders. Diet quality was poor in this sample, with 60% in the lowest category of overall diet quality. Overall diet quality and fruit and vegetable quality significantly attenuated the association between PM 2.5 and prevalence of chronic cough and phlegm. Sauce/condiment intake was associated with a greater effect of PM 2.5 on COPD prevalence. No other moderating effects were significant. The moderating effects of overall diet quality and vegetable and fruit intake aligned with a priori hypotheses, suggesting potential protective benefits. While more evidence is needed to confirm these findings, improving diets, especially fruit and vegetable intake, may provide some protection against the effects of smoke exposure from fire events., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Thara Govindaraju, Matthew Carroll, Brigitte M. Borg, Catherine L. Smith, Caroline X. Gao, David Brown, David Poland, Shantelle Allgood, Jillian F. Skin, Michael J. Abrasion, Tyler J. Lane reports financial support was provided by Victoria Department of Health. Michael J. Abramson reports a relationship with Pfizer, Boehringer-Ingelheim, Sanofi, GSK that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aim: There are few long-term studies of respiratory health effects of landscape fires, despite increasing frequency and intensity due to climate change. We investigated the association between exposure to coal mine fire PM 2.5 and fractional exhaled nitric oxide (FeNO) concentration 7.5 years later., Methods: Adult residents of Morwell, who were exposed to the 2014 Hazelwood mine fire over 6 weeks, and unexposed residents of Sale, participated in the Hazelwood Health Study Respiratory Stream in 2021, including measurements of FeNO concentration, a marker of eosinophilic airway inflammation. Individual exposure to coal mine fire PM 2.5 was modelled and mapped to time-location diaries. The effect of exposure to PM 2.5 on log-transformed FeNO in exhaled breath was investigated using multivariate linear regression models in the entire sample and stratified by potentially vulnerable subgroups., Results: A total of 326 adults (mean age: 57 years) had FeNO measured. The median FeNO level (interquartile range [IQR]) was 17.5 [15.0] ppb, and individual daily exposure to coal mine fire PM 2.5 was 7.2 [13.8] µg/m 3 . We did not identify evidence of association between coal mine fire PM 2.5 exposure and FeNO in the general adult sample, nor in various potentially vulnerable subgroups. The point estimates were consistently close to zero in the total sample and subgroups., Conclusion: Despite previous short-term impacts on FeNO and respiratory health outcomes in the medium term, we found no evidence that PM 2.5 from the Hazelwood coal mine fire was associated with any long-term impact on eosinophilic airway inflammation measured by FeNO levels., (© 2024. The Author(s).)

Randomized controlled trials can be used to generate evidence on the efficacy and safety of new treatments in eating disorders research. Many of the trials previously conducted in this area have been deemed to be of low quality, in part due to a number of practical constraints. This article provides an overview of established and more innovative clinical trial designs, accompanied by pertinent examples, to highlight how design choices can enhance flexibility and improve efficiency of both resource allocation and participant involvement. Trial designs include individually randomized, cluster randomized, and designs with randomizations at multiple time points and/or addressing several research questions (master protocol studies). Design features include the use of adaptations and considerations for pragmatic or registry-based trials. The appropriate choice of trial design, together with rigorous trial conduct, reporting and analysis, can establish high-quality evidence to advance knowledge in the field. It is anticipated that this article will provide a broad and contemporary introduction to trial designs and will help researchers make informed trial design choices for improved testing of new interventions in eating disorders. PUBLIC SIGNIFICANCE: There is a paucity of high quality randomized controlled trials that have been conducted in eating disorders, highlighting the need to identify where efficiency gains in trial design may be possible to advance the eating disorder research field. We provide an overview of some key trial designs and features which may offer solutions to practical constraints and increase trial efficiency., (© 2024 The Authors. International Journal of Eating Disorders published by Wiley Periodicals LLC.)

Bacteria and fungi are ubiquitous throughout built environments and are suspended in the air, potentially affecting human health. However, the impacts of climate zones on the diversity, structure, and stochastic assembly of indoor airborne microbes remain unknown. This study comprehensively analyzed indoor airborne microbes across five climate zones in China during the summer and winter using high-throughput sequencing. The diversity and structure of indoor airborne communities vary across climatic zones. A random forest model was used to identify biomarkers in different climate zones. The results showed no relationship between the biomarkers and their rankings in mean relative abundance. The Sloan neutral model fitting results indicated that the impact of climate zones on the stochastic process in the assembly of indoor airborne microbes was considerably more important than that of seasons. Additionally, the influence of seasons on the diversity, structure, and stochastic assembly process of indoor airborne microbes differed among different climate zones. The diversity, structure, and stochastic assembly processes of bacteria present distinctive outcomes in climate zones and seasons compared with those of fungi. Overall, these findings indicate that customized strategies are necessary to manage indoor airborne microbial communities in each climate zone, season, and for specific microbial species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Staphylococcus aureus is a common pathogenic microorganism in humans and animals. Type II NADH oxidoreductase (NDH-2) is the only NADH:quinone oxidoreductase present in this organism and represents a promising target for the development of anti-staphylococcal drugs. Recently, myricetin, a natural flavonoid from vegetables and fruits, was found to be a potential inhibitor of NDH-2 of S. aureus . The objective of this study was to evaluate the inhibitory properties of myricetin against NDH-2 and its impact on the growth and expression of virulence factors in S. aureus ., Results: A screening method was established to identify effective inhibitors of NDH-2, based on heterologously expressed S. aureus NDH-2. Myricetin was found to be an effective inhibitor of NDH-2 with a half maximal inhibitory concentration (IC 50 ) of 2 μM. In silico predictions and enzyme inhibition kinetics further characterized myricetin as a competitive inhibitor of NDH-2 with respect to the substrate menadione (MK). The minimum inhibitory concentrations (MICs) of myricetin against S. aureus strains ranged from 64 to 128 μg/mL. Time-kill assays showed that myricetin was a bactericidal agent against S. aureus . In line with being a competitive inhibitor of the NDH-2 substrate MK, the anti-staphylococcal activity of myricetin was antagonized by MK-4. In addition, myricetin was found to inhibit the gene expression of enterotoxin SeA and reduce the hemolytic activity induced by S. aureus culture on rabbit erythrocytes in a dose-dependent manner., Conclusions: Myricetin was newly discovered to be a competitive inhibitor of S. aureus NDH-2 in relation to the substrate MK. This discovery offers a fresh perspective on the anti-staphylococcal activity of myricetin.

Background: Chronic, low-intensity air pollution exposure has been consistently associated with increased atherosclerosis in adults. However, there was limited research regarding the implications of acute, high-intensity air pollution exposure during childhood. We aimed to determine whether there were any associations between early-life exposure to such an episode and early-life vascular function changes., Methods: We conducted a prospective cohort study of children (<9 years old) who lived in the vicinity of the Hazelwood coal mine fire (n = 206). Vascular function was measured using noninvasive diagnostic methods including carotid intima-media thickness and pulse wave velocity (PWV). Exposure estimates were calculated from prognostic models and location diaries during the exposure period completed by each participant's parent. Linear mixed-effects models were used to determine whether there were any associations between exposure and changes in vascular outcomes at the 3- and 7-year follow-ups and over time., Results: At the 7-year follow-up, each 10 μg/m 3 increase in daily PM 2.5 in utero was associated with increased PWV ( β = 0.13 m/s; 95% confidence interval [CI] = 0.02, 0.24; P = 0.02). The association between in utero exposure to daily PM 2.5 was not altered by adjustment for covariates, body mass index, and maternal fire stress. Each 1 µg/m 3 increase in background PM 2.5 was associated with increased PWV ( β = 0.68 m/s; 95% CI = 0.10, 1.26; P = 0.025), in children from the in utero exposure group. There was a trend toward smaller PWV ( β = -0.17 m/s; 95% CI = -0.366, 0.02) from the 3- to 7-year follow-up clinic suggesting that the deficits observed previously in children exposed postnatally did not persist., Conclusion: There was a moderate improvement in vascular stiffness of children exposed to PM 2.5 from a local coal mine fire in infancy. There was a mild increase in vascular stiffness in children exposed to PM 2.5 from a local coal mine fire while their mothers were pregnant., Competing Interests: E.J.H., A.B., S.A., A.J.W., M.D., G.J.W., C.X.G., K.N., F.H.J., and G.R.Z. declare that they have no conflicts of interest with regard to the content of this report. M.J.A. reports a relationship with Pfizer Global Research and Development that includes funding grants. M.J.A. reports a relationship with Boehringer Ingelheim GmbH that includes funding grants. M.J.A. reports a relationship with Sanofi Australia that includes consulting or advisory, and funding grants. M.J.A. reports a relationship with GlaxoSmithKline that includes funding grants and speaking and lecture fees., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Substantial evidence suggest that chronic consumption of high-fat diets (HFDs) can lead to obesity, abnormal metabolism, as well as cognitive impairment. Molecular and cellular changes regarding hippocampal dysfunctions have been identified in multiple HFD animal models. Therefore, in-depth identification of expression changes of hippocampal proteins is critical for understanding the mechanism of HFD-induced cognitive deficits. In this study, we fed 3-week-old male mice with HFD for 3 months to generate obese mice who exhibit systemic metabolic abnormality and learning and memory decline. Using an iTRAQ-labeled proteomic analysis, we identified a total of 82 differentially expressed proteins (DEPs) in the hippocampus upon HFD with 35 up-regulated proteins and 47 down-regulated proteins. Functional enrichment indicated that these DEPs were predominantly enriched in regulation of catabolic process, dendritic shaft, neuron projection morphogenesis and GTPase regulator activity. Protein-protein interaction enrichment showed that the DEPs are mostly enriched in postsynaptic functions; and of them, six proteins (i.e., DLG3, SYNGAP1, DCLK1, GRIA4, GRIP1, and ARHGAP32) were involved in several functional assemblies of the postsynaptic density including G-protein signaling, scaffolding and adaptor, kinase and AMPA signaling, respectively. Collectively, our findings suggest that these DEPs upon HFD might contribute to memory decline by disturbing neuronal and postsynaptic functions in the hippocampus., Competing Interests: Declaration of competing interest All authors declare no conflict of interest in this study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Despite increasing vaccination rates, the incidence of breakthrough infections with COVID-19 has increased due to the continued emergence of new variants of the SARS-CoV-2 coronavirus. Therefore, Non-pharmaceutical interventions remain the most effective measures for coping with the ever-changing pandemic. The lifting of compulsory interventions has made individuals primary responsibility for their own health, which highlights the importance of increasing awareness of the infection risk from the environment in which they live and their individual behaviors. We systematically searched PubMed, Web of Science, ScienceDirect, and Scopus on April 17, 2023, for all studies reporting COVID-19 outbreaks in public indoor venues. The study outcome was the attack rate. A total of 42 studies, which included cross-sectional studies, cohort studies, and case studies, reporting data on 1951 confirmed cases in 64 COVID-19 outbreaks satisfied the meta-analysis and were included in the review. A random-effect model was used in the meta-analysis, and subgroup analyses were conducted to investigate factors affecting attack rates. We found a strong level of evidence (p < 0.01) supporting a higher pooled attack rate in recreation-related venues (0.44, 95% CI: 0.30 to 0.60) than in work-related venues (0.21, 95% CI: 0.16 to 0.27). Compared to those outbreaks without that, outbreaks with high-intensity exercise, vocalization, contact behavior, or close body proximity had a higher attack rate of 0.51, 0.55, 0.33, and 0.39, respectively. Further studies suggest that different attack rates across different types of settings may be the result of heterogeneity in exposed people's behaviors. There were significant heterogeneities that may limit the interpretation of connections between influencing factors and outbreak outcomes. The identification of key behaviors that may contribute to transmission risk, and their correlation with venue type, has important implications for the development of future public health interventions and individual prevention strategies for respiratory infectious diseases such as COVID-19., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: In 2014, the Hazelwood coalmine fire shrouded the regional Australian town of Morwell in smoke and ash for 6 weeks. One of the fire's by-products, PM 2.5 , is associated with an increased risk of COVID-19 and severe disease. However, it is unclear whether the effect persisted for years after exposure. In this study, we surveyed a cohort established prior to the pandemic to determine whether PM 2.5 from the coalmine fire increased long-term vulnerability to COVID-19 and severe disease., Methods: From August to December 2022, 612 members of the Hazelwood Health Study's adult cohort, established in 2016/17, participated in a follow-up survey that included standardized items to capture COVID-19 cases, as well as questions about hospitalization and vaccinations. Associations were evaluated in crude and adjusted logistic regression models., Results: A total of 268 (44%) participants self-reported or met symptom criteria for having had COVID-19 at least once. All models found a positive association, with odds of COVID-19 increasing by between 4% and 30% for a 10 μg/m 3 increase in coalmine fire-related PM 2.5 exposure. However, the association was significant in only 2 of the 18 models. There were insufficient hospitalizations to examine severity (n = 7; 1%)., Conclusion: The findings are inconclusive on the effect of coalmine fire-related PM 2.5 exposure on long-term vulnerability to COVID-19. Given the positive association that was robust to modelling variations as well as evidence for a causal mechanism, it would be prudent to treat PM 2.5 from fire events as a long-term risk factor until more evidence accumulates., (© 2023 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Background: Evidence on the relationship between air pollution and allergic sensitisation in childhood is inconsistent, and this relationship has not been investigated in the context of smoke events that are predicted to increase with climate change. Thus, we aimed to evaluate associations between exposure in two early life periods to severe levels of particulate matter with an aerodynamic diameter < 2.5 μm (PM 2.5 ) from a mine fire, background PM 2.5 , and allergic sensitisation later in childhood., Methods: We measured specific immunoglobulin E (IgE) levels for seven common aeroallergens as well as total IgE levels in a cohort of children who had been exposed to the Hazelwood coal mine fire, either in utero or during their first two years of life, in a regional area of Australia where ambient levels of PM 2.5 are generally low. We estimated personal exposure to fire-specific emissions of PM 2.5 based on a high-resolution meteorological and pollutant dispersion model and detailed reported movements of pregnant mothers and young children during the fire. We also estimated the usual background exposure to PM 2.5 at the residential address at birth using a national satellite-based land-use regression model. Associations between both sources of PM 2.5 and sensitisation to dust, cat, fungi, and grass seven years after the fire were estimated with logistic regression, while associations with total IgE levels were estimated with linear regression., Results: No association was found between the levels of exposure at either developmental stage to fire-related PM 2.5 and allergic sensitisation seven years after the event. However, levels of background exposure were positively associated with sensitisation to dust (OR = 1.90, 95%CI = 1.12,3.21 per 1 μg/m 3 )., Conclusions: Chronic but low exposure to PM 2.5 in early life could be more strongly associated with allergic sensitisation in childhood than time-limited high exposure levels, such as the ones experienced during landscape fires., (© 2023. The Author(s).)

Background: Episodic spikes in air pollution due to landscape fires are increasing, and their potential for longer term health impacts is uncertain., Objective: Our objective is to evaluate associations between exposure in utero and in infancy to severe pollution from a mine fire, background ambient air pollution, and subsequent hospital care., Methods: We linked health records of births, emergency department (ED) visits, and hospitalizations of children born in the Latrobe Valley, Australia, 2012-2015, which included a severe pollution episode from a mine fire (9 February 2014 to 25 March 2014). We assigned modeled exposure estimates for fire-related and ambient particulate matter with an aerodynamic diameter of 2.5 μ m ( PM 2.5 ) to residential address. We used logistic regression to estimate associations with hospital visits for any cause and groupings of infectious, allergic, and respiratory conditions. Outcomes were assessed for the first year of life in the in utero cohort and the year following the fire in the infant cohort. We estimated exposure-response for both fire-related and ambient PM 2.5 and also employed inverse probability weighting using the propensity score to compare exposed and not/minimally exposed children., Results: Prenatal exposure to fire-related PM 2.5 was associated with ED presentations for allergies/skin rash [odds ratio ( OR ) = 1.34 , 95% confidence interval (CI): 1.01, 1.76 per 240   μ g / m 3 increase]. Exposure in utero to ambient PM 2.5 was associated with overall presentations ( OR = 1.18 , 95% CI: 1.05, 1.33 per 1.4   μ g / m 3 ) and visits for infections (ED: OR = 1.13 , 95% CI: 0.98, 1.29; hospitalizations: OR = 1.23 , 95% CI: 1.00, 1.52). Exposure in infancy to fire-related PM 2.5 compared to no/minimal exposure, was associated with ED presentations for respiratory ( OR = 1.37 , 95% CI: 1.05, 1.80) and infectious conditions (any: OR = 1.21 , 95% CI: 0.98, 1.49; respiratory-related: OR = 1.39 , 95% CI: 1.05, 1.83). Early life exposure to ambient PM 2.5 was associated with overall ED visits ( OR = 1.17 , 95% CI: 1.05, 1.30 per 1.4   μ g / m 3 increase)., Discussion: Higher episodic and lower ambient concentrations of PM 2.5 in early life were associated with visits for allergic, respiratory, and infectious conditions. Our findings also indicated differences in associations at the two developmental stages. https://doi.org/10.1289/EHP12238.

Australia's Fifth National Mental Health Plan required governments to report, not only on the progress of changes to mental health service delivery, but to also plan for services that should be provided. Future population demand for treatment and care is challenging to predict and one solution involves modelling the uncertain demands on the system. Modelling can help decision-makers understand likely future changes in mental health service demand and more intelligently choose appropriate responses. It can also support greater scrutiny, accountability and transparency of these processes. Australia has an emerging national capacity for systems modelling in mental health which can enhance the next phase of mental health reform. This paper introduces concepts useful for understanding mental health modelling and identifies where modelling approaches can support health service planners to make evidence-informed decisions regarding planning and investment for the Australian population., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Incidence of psychosis varies geographically due to factors such as social disadvantage. Whether this influences the clinical presentation and/or engagement of those experiencing psychosis remains relatively understudied. This study analysed data from young people across Australia accessing ultra-high risk (UHR) or first episode psychosis (FEP) services delivered through the headspace Early Psychosis (hEP) program between June 2017 and March 2021. The cohort was categorised into low, middle, and high tertiles of social disadvantage using the Index of Relative Socioeconomic Disadvantage (IRSD). Data from 3089 participants aged 15-25 were included (1515 UHR, 1574 FEP). The low and middle tertiles for both cohorts had greater percentages of those not in education or employment (NEET), with First Nations or culturally and linguistically diverse backgrounds. Clinical presentations to services were similar across all tertiles in both cohorts, however, functioning at presentation varied significantly within the FEP cohort. Significantly lower numbers of direct services were provided in the low tertile of both cohorts, with significantly poorer engagement in the initial three-months also occurring for these young people. This variation in early psychosis service patterns associated with geographical variation in social deprivation demonstrates the need for further research and fine tuning of national early psychosis services., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Purpose: Use of alcohol and other substances is a multifaceted issue impacting young people across multiple life domains. This paper aims to elucidate patterns of substance use and associated demographic and clinical factors among young people seeking treatment for their mental health., Methods: Young people (12-25 years old) were recruited from five youth-specific primary mental health ("headspace") services in Australia. Self-reported substance use and harms in the past 3 months were measured using WHO-ASSIST. Network analyses were conducted to evaluate interrelationships between use and harms associated with different substances. Subgroups were then identified based on whether participants reported using high centrality substances, and associated demographic and clinical factors were assessed with multinomial logistic regression., Results: 1107 youth participated. 70% reported use of at least one substance in the past 3 months, with around 30% of those reporting related health, social, legal or financial problems. Network analysis highlighted substantial interconnections between use and harm indicators for all substances, with amphetamine-type stimulants (ATS) and cannabis being high central substances. Higher levels of substance use and harms were reported in subgroups with ATS or cannabis use and different risk factors were associated with these subgroups., Conclusions: Findings highlight the importance of screening for substance use in youth primary mental healthcare settings, offering a key opportunity for early intervention. Clinicians should be aware of the inner connections of use and harms of different drugs and the role of cannabis and amphetamine use as a marker for more substance use profiles., (© 2023. The Author(s).)

Background: Substance use remains a barrier to recovery for young people accessing early intervention services for psychosis. While correlates of use have been explored in populations experiencing a first episode of psychosis (FEP), sample sizes have been small and less research assesses cohorts at ultrahigh risk of psychosis (UHR)., Methods: This study uses data from a naturalistic cohort including UHR and FEP participants (N = 1252) to elucidate clinical correlates of use in the past 3 months of any illicit substance, amphetamine-type stimulants (ATS), cannabis, and tobacco. Moreover, network analysis based on use of these substances and additionally alcohol, cocaine, hallucinogens, sedatives, inhalants, and opioids was completed., Results: Young people with FEP used substances at significantly higher rates than those at UHR. High concurrence of use was seen between substances. In the FEP group, participants who had used any illicit substance, ATS, and/or tobacco had increased positive symptoms and decreased negative symptoms. Young people with FEP who used cannabis had increased positive symptoms. In the UHR group, participants who had used any illicit substance, ATS, and/or cannabis in the past 3 months showed decreased negative symptoms compared to those who had not., Conclusion: A distinct clinical picture of more florid positive symptoms and alleviated negative symptoms seen in those who use substances in the FEP group appears muted in the UHR cohort. Treating young people at UHR in early intervention services represents the earliest opportunity to address substance use early to improve outcomes., (© 2023. The Author(s).)

Cluster analyzes have been widely used in mental health research to decompose inter-individual heterogeneity by identifying more homogeneous subgroups of individuals. However, despite advances in new algorithms and increasing popularity, there is little guidance on model choice, analytical framework and reporting requirements. In this paper, we aimed to address this gap by introducing the philosophy, design, advantages/disadvantages and implementation of major algorithms that are particularly relevant in mental health research. Extensions of basic models, such as kernel methods, deep learning, semi-supervised clustering, and clustering ensembles are subsequently introduced. How to choose algorithms to address common issues as well as methods for pre-clustering data processing, clustering evaluation and validation are then discussed. Importantly, we also provide general guidance on clustering workflow and reporting requirements. To facilitate the implementation of different algorithms, we provide information on R functions and libraries., Competing Interests: Declaration of Competing Interest This study was not funded. The author(s) declare that there were no conflicts of interest with respect to the authorship or the publication of this article., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Wildfires cause significant physical and mental ill-health. How physical and mental symptoms interact following wildfire smoke exposure is unclear, particularly in the context of repeated exposures. In this cross-sectional study we investigated how posttraumatic stress and general psychological distress associated with somatic symptoms in a community exposed to multiple smoke events., Methods: A random weighted sample of 709 adults exposed to smoke during the 2014 Hazelwood coal mine fire in south-eastern Australia completed a survey in 2020. The survey coincided with the Black Summer wildfires that caused a similar period of smoke haze in the region. Participants self-reported somatic symptoms (PHQ-15) and mine fire-related posttraumatic stress (IES-R) experienced over the previous week, general psychological distress (K10) experienced over the previous four weeks, lifetime health diagnoses and demographic information. Associations between posttraumatic stress, general psychological distress, and each PHQ-15 somatic symptom were analysed using ordinal logistic regression models., Results: Overall, 36.2% of participants reported moderate- or high-level somatic symptomology. The most frequent somatic symptoms were fatigue, limb pain, trouble sleeping, back pain, headaches, and shortness of breath. After controlling for confounding factors, general psychological distress and posttraumatic stress were independently associated with all somatic symptoms (except menstrual problems in females for posttraumatic stress)., Conclusions: Results highlight the high prevalence of somatic symptoms and their association with general psychological distress and posttraumatic stress within a community in the midst of a second large-scale smoke event. It is essential that healthcare providers and public health authorities consider the interconnections of these conditions when supporting communities affected by climate-related disasters., (© 2023. BioMed Central Ltd., part of Springer Nature.)

With the rapid development of synthetic biology, various whole-cell biosensors have been designed as valuable biological devices for the selective and sensitive detection of toxic heavy metals in environmental water. However, most proposed biosensors are based on fluorescent and bioluminescent signals invisible to the naked eye. The development of visible pigment-based biosensors can address this issue. The pbr operon from Klebsiella pneumoniae is selectively induced by bioavailable Pb(II). In the present study, the proviolacein biosynthetic gene cluster was transcriptionally fused to the pbr Pb(II) responsive element and introduced into Escherichia coli . The resultant biosensor responded to Pb(II) in a time- and dose-dependent manner. After a 5-h incubation with Pb(II), the brown pigment was produced, which could be extracted into n-butanol. Extra hydrogen peroxide treatment during n-butanol extract resulted in the generation of a stable green pigment. An increased brown signal was observed upon exposure to lead concentrations above 2.93 nM, and a linear regression was fitted from 2.93 to 3,000 nM. Extra oxidation significantly decreased the difference between parallel groups. The green signal responded to as low as 0.183 nM Pb(II), and a non-linear regression was fitted in a wide concentration range from 0.183 to 3,000 nM. The specific response toward Pb(II) was not interfered with by various metals except for Cd(II) and Hg(II). The PV-based biosensor was validated in monitoring bioaccessible Pb(II) spiked into environmental water. The complex matrices did not influence the regression relationship between spiked Pb(II) and the dual-color signals. Direct reading with the naked eye and colorimetric quantification enable the PV-based biosensor to be a dual-color and low-cost bioindicator for pollutant heavy metal., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhu, Guo, Ma, Lin, Wang, Gao, Liu, Zhang, Luo and Hui.)

Background: Due to climate change, landscape fires account for an increasing proportion of air pollution emissions, and their impacts on primary and pharmaceutical care are little understood., Objectives: To evaluate associations between exposure in two early life periods to severe levels of PM 2.5 from a mine fire, background PM 2.5 , and primary and pharmaceutical care., Methods: We linked records of births, general practitioner (GP) presentations and prescription dispensing for children born in the Latrobe Valley, Australia, 2012-2014, where a severe mine fire occurred in February-March 2014 in an area with otherwise low levels of ambient PM 2.5 . We assigned modelled exposure estimates for fire-related (cumulative over the fire and peak 24-hour average) and annual ambient PM 2.5 to residential address. Associations with GP presentations and dispensing of prescribed medications in the first two years of life (exposure in utero) and in the two years post-fire (exposure in infancy) were estimated using two-pollutant quasi-Poisson regression models., Results: Exposure in utero to fire-related PM 2.5 was associated with an increase in systemic steroid dispensing (Cumulative: IRR = 1.11, 95%CI = 1.00-1.24 per 240 μg/m 3 ; Peak: IRR = 1.15, 95%CI = 1.00-1.32 per 45 μg/m 3 ), while exposure in infancy was associated with antibiotic dispensing (Cumulative: IRR = 1.05, 95%CI = 1.00-1.09; Peak: IRR = 1.06, 95%CI = 1.00-1.12). Exposure in infancy to ambient PM 2.5 , despite relatively low levels from a global perspective (Median = 6.1 μg/m 3 ), was associated with an increase in antibiotics (IRR = 1.10, 95%CI = 1.01-1.19 per 1.4 μg/m 3 ) and in GP presentations (IRR = 1.05, 95%CI = 1.00-1.11), independently from exposure to the fire. We also observed differences in associations between sexes with GP presentations (stronger in girls) and steroid skin cream dispensing (stronger in boys)., Discussion: Severe medium-term concentrations of PM 2.5 were linked with increased pharmaceutical treatment for infections, while chronic low levels were associated with increased prescriptions dispensed for infections and primary care usage. Our findings also indicated differences between sexes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Fay Johnston reports financial support was provided by Victoria Department of Health and Human Services. Shyamali Dharmage reports a relationship with AstraZeneca plc that includes: funding grants. Shyamali Dharmage reports a relationship with GSK plc that includes: funding grants., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: The authors aimed to evaluate changes in use of government-subsidized primary mental health services, through the Medicare Benefits Schedule (MBS), by young people during the first year of the COVID-19 pandemic in Australia and whether changes were associated with age, sex, socioeconomic status, and residence in particular geographical areas., Methods: Interrupted time-series analyses were conducted by using quarterly mental health MBS service data (all young people ages 12-25 years, 2015-2020) for individual Statistical Area Level 3 areas across Australia. The data captured >22.4 million service records. Meta-analysis and meta-regression models estimated the pandemic interruption effect at the national level and delineated factors influencing these estimates., Results: Compared with expected prepandemic trends, a 6.2% (95% CI=5.3%-7.2%) increase was noted for all young people in use of MBS mental health services in 2020. Substantial differences were found between age and sex subgroups, with a higher increase among females and young people ages 18-25. A decreasing trend was observed for males ages 18-25 (3.5% reduction, 95% CI=2.5%-4.5%). The interruption effect was strongly associated with socioeconomic status. Service uptake increased in areas of high socioeconomic status, with smaller or limited uptake in areas of low socioeconomic status., Conclusions: During 2020, young people's use of primary mental health services increased overall. However, increases were inequitably distributed and relatively low, compared with increases in population-level mental health burden. Policy makers should address barriers to primary care access for young people, particularly for young males and those from socioeconomically disadvantaged backgrounds., Competing Interests: Dr. Hickie reports support for community-based projects from AstraZeneca, Eli Lily, Pfizer, Servier, and Wyeth. He is chief scientific adviser to and an equity shareholder in InnoWell Pty. Ltd. The other authors report no financial relationships with commercial interests.

Oleanolic acid (OA) is a five-ring triterpenoid compound, which is widely present in plants. Due to a wide range of pharmacological activities, oleanolic acid has attracted more and more attention. However, oleanolic acid is insoluble in water and has low bioavailability, which limits its clinical application. In this review, we focus on summarizing the anti-cancer activity and mechanism of the A ring or C-28 carboxyl modified derivatives of OA since 2015, to determine the strength of its anti-cancer effectiveness and evaluate whether it could be used as a clinical anti-cancer drug.

Background: Climate change represents a serious threat to human health, including mental health, due to both the traumatizing effects of extreme climate events and the psychological effect of worry about climate change., Objectives: This scoping review aims to search the literature for original research investigating mental health and climate-related negative emotions in young people. Findings will help to understand the current landscape, gaps in the literature, and provide recommendations for future youth mental health research and practice., Methods: A scoping review of the literature examining negative emotions associated with climate change in young people was undertaken. Studies published prior to March 2022 were included if they examined mental ill-health (e.g., symptoms of depression or anxiety) or negative emotions (e.g., distress, worry, concern) associated with the threat of climate change., Results: Of 3939 articles screened, 26 met the inclusion criteria. Together, studies show that young people are worried about climate change. Negative emotions about climate change were correlated with symptoms of mental ill-health. Studies also explored coping strategies young people use to manage their distress caused by climate change., Discussion: The limited literature in this area indicates a key gap in youth mental health research. While available evidence suggests that young people are concerned about climate change, more research is needed on the relationship between climate-related negative emotions and mental ill-health. Clinicians should assess for and address climate-related negative emotions in young people. Mental health leaders are urged to advocate for actions to mitigate the mental health impact of climate change., (© 2023 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Objective: We describe a research program to advance youth mental health service research in Australia, addressing two core knowledge gaps: the lack of available routine outcome measures and lack of understanding of how to assess and monitor complexity and heterogeneity in illness presentation and trajectory., Conclusions: Our research identifies better routine outcome measures (ROM) that are: designed specifically for the developmental nuances of the 12-25-year age range; multidimensional; and meaningful to young people, their carers, and service providers. Alongside much-needed new measures of complexity and heterogeneity, these tools will inform service providers to better meet the needs of young people presenting with mental health problems.

Background: Rheumatoid arthritis (RA) joint inflammation severely affects joint function and quality of life in patients and leads to joint deformities and limb disability. The non-steroidal anti-inflammatory drugs used in the treatment of RA do not fully control the progression of joint inflammation and bone destruction and have notable adverse reactions. Traditional Chinese medicine formula JuanBiQiangGu Granules (JBQG) are commonly used for the treatment of RA inflammation and delay of bone destruction, but has not been evaluated through high-quality clinical studies. There is a pressing need for well-designed, randomized, parallel, controlled clinical studies to evaluate the exact effect of JBQG on RA joint inflammation and improvement of patient quality of life. Methods: This is a randomized, parallel, controlled clinical study in which 144 patients with rheumatoid arthritis who met the inclusion criteria were randomly assigned to 2 groups in a 1:1 ratio. The JBQG group received methotrexate 7.5 mg qw and JBQG granules 8 mg tid, while the MTX group received methotrexate 7.5 mg qw. The endpoint was 12 weeks after treatment. Relevant indices at baseline, 4 weeks, 8 weeks, and 12 weeks after treatment were observed and recorded, and DAS28-ESR, HAQ-DI, and Sharp scores were recorded for each patient. Blood samples were collected to test for CRP, ESR, TNF-α, IL-1β, IL-6, IL-17, and INF-γ, and adverse reactions and liver and kidney function (AST, ALT, Cr, BUN) were recorded for safety assessment. After 12 weeks of treatment, the effect of JBQG granules on disease activity, improvement in bone damage, and patient quality of life scores and safety in RA patients were evaluated. Results: A total of 144 subjects completed treatment (71 in the JBQG group and 73 in the MTX group) and were included in the analysis. At baseline, there were no significant differences between the groups in terms of the observed indicators ( p > 0.05). After treatment, 76.06% of patients in the JBQG group had DAS28-ESR levels below or equal to Low, including 45.07% in Remission and 5.63% in High, compared to 53.1% in the MTX group below or equal to Low, 12.33% in Remission, and 17.81% in High. CRP was significantly reduced (8.54 ± 5.87 vs. 11.86 ± 7.92, p < 0.05, p = 0.005), ESR was significantly reduced (15.1 ± 6.11 vs. 21.96 ± 9.19, p < 0.0001), TNF-α was significantly reduced (1.44 ± 0.83 vs. 1.85 ± 1.07, p < 0.05, p = 0.011), IL-17 was significantly reduced (0.53 ± 0.33 vs. 0.71 ± 0.38, p < 0.05, p = 0.004), and INF-γ was significantly reduced (3.2 ± 1.51 vs. 3.89 ± 1.77, p < 0.05, p = 0.014). The median (IQR) OPG in the JBQG group was 2.54 (2.21-3.01), significantly higher than in the MTX group 2.06 (1.81-2.32), p < 0.0001), and the median (IQR) β -CTX in the JBQG group was 0.4 (0.32-0.43), significantly lower than in the MTX group 0.55 (0.47-0.67), p < 0.0001). The median (IQR) VSA scores were 2 (1-3), a decrease from 3 (2-4) in the MTX group ( p < 0.0001). The median (IQR) Sharp scores were 1 (1-2), a decrease from 2 (1-2) in the MTX group, but the difference was not statistically significant ( p > 0.05, p = 0.28). The median (IQR) HAQ-DI scores were 11 (8-16), significantly lower than in the MTX group 26 (16-30) ( p < 0.0001). The median (IQR) AST in the JBQG group was 16 (12-20), with a significant difference compared to the MTX group 19 (13-25) ( p < 0.01, p = 0.004); the median (IQR) ALT in the JBQG group was 14 (10-18), with a significant difference compared to the MTX group 16 (11-22.5) ( p < 0.05, p = 0.015). There were no statistically significant differences in Cr or BUN ( p > 0.05). Conclusion: JuanBiQiangGu Granules can be used to treat patients with rheumatoid arthritis, alleviate joint inflammation, reduce the incidence of adverse reactions to methotrexate, and has good safety. Clinical Trial Registration: http://www.chinadrugtrials.org.cn/index.html; identifier: ChiCTR2100046373., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ran, Xu, Han, Wang, A, Cao, Meng, Zhang, Xin, Qiu, Xiang, Pei, Gao, Shen, Zhong, Xu, Bian, Xie, Shi, Sun and Xiao.)

Background: In 2014, wildfires ignited a coal mine in Australia, burning for 6 weeks, releasing large amounts of fine particulate matter ≤2.5 μm in diameter (PM 2.5 ). We investigated the association between individual PM 2.5 exposure and emergency department presentations (EDPs) within 5 years post-fire., Methods: Survey and exposure data for 2725 residents from an exposed and unexposed town were linked with ED administrative data from 2009 to 2019. The association between individual PM 2.5 and EDPs was assessed using recurrent survival analysis., Results: A 10 μg/m 3 increase in PM 2.5 was associated with a 10% increase in respiratory EDPs (HR = 1.10; 95%CI:1.00-1.22) over 5 years post-fire. Increased risks of EDPs for ischaemic heart disease (HR = 1.39; 95%CI:1.12-1.73), atherothrombotic disease (HR = 1.27; 95%CI:1.08-1.50), and cardiovascular disease (HR = 1.10, 95%CI:0.99-1.22) were evident within 2.5 years., Conclusion: PM 2.5 exposure from a 6-week mine fire increased the 5-year risk of respiratory conditions. An increased risk of CVD within 2.5 years post-fire subsided after this time., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Michael Abramson reports a relationship with Pfizer that includes: funding grants. Michael Abramson reports a relationship with Boehringer-Ingelheim that includes: funding grants. Michael Abramson reports a relationship with Sanofi that includes: consulting or advisory and funding grants. Michael Abramson reports a relationship with GSK that includes: funding grants and speaking and lecture fees. Dion Stub reports a relationship with National Heart Foundation of Australia that includes: funding grants. Yuming Guo reports a relationship with Australian National Health and Medical Research Council that includes: funding grants., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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 (PM 2.5 ) 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]. PM 2.5 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., (© 2023 The Authors. Journal of Traumatic Stress published by Wiley Periodicals LLC on behalf of International Society for Traumatic Stress Studies.)

Introduction: In Australian youth primary mental health settings it is unclear as to the rates and correlates of tobacco use at service entry., Aims and Methods: We aimed to delineate the prevalence and correlates of recent tobacco use (eg, cigarettes, chewing tobacco, cigars, etc) in the past 3 months in young people at their first presentation to primary mental health services as a function of age. Cross-sectional self-report measures were collected using a tablet device from young people presenting to one of five Australian primary mental health (headspace) services. Logistic regression assessed correlates of past 3-month tobacco use in adolescents (12-17 years) and young adults (18-25 years)., Results: Regular (at least monthly) tobacco use in the past 3 months was found in 23.4% (n = 247, N = 1055) of the sample. Increasing age (odds ratio [OR] =1.47 per year; 95% confidence interval [CI]: 1.15 to 1.89), male sex (OR = 1.98; 95% CI: 1.02 to 3.83), being in a relationship (OR = 1.96; 95% CI: 1.01 to 3.82), and poorer functioning (OR = 0.95 per unit Social and Occupational Functioning Assessment Scale increase; 95% CI: 0.91 to 0.99) predicted regular tobacco use in adolescents, but not in young adults. Living in a regional location (OR = 2.10; 95% CI: 1.40 to 3.13) and not studying (OR = 0.47; 95% CI: 0.31 to 0.73) predicted tobacco use in young adults. Having a diagnosed mental illness other than depression and/or anxiety predicted tobacco use in both groups (adolescents OR = 2.49; 95% CI: 1.26 to 4.94; young adults OR = 1.80; 95% CI: 1.13 to 2.89)., Conclusions: Nearly a quarter of young people with mental illness are using tobacco, supporting the need for early intervention approaches. Adapting treatment targets by age could improve the impact of interventions in adolescents versus young adults. Poor functioning and lack of engagement in education were associated with tobacco use in both age groups, respectively; however, more research is needed to determine the direction of these relationships., Implications: Young people with mental illness have a high prevalence of recent tobacco use and this is evident when they first present to youth primary mental health services. Youth-oriented mental health settings may provide a unique window for tobacco use prevention and early intervention to reduce smoking in people with mental illness, a priority population. Age-specific targeted approaches might be needed in adolescents and young adults., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: First-episode psychosis (FEP) is characterised by wide heterogeneity in terms of symptom presentation and illness course. However, the heterogeneity of quality of life (QoL) in FEP is not well understood. We investigated whether subgroups can be identified using participants' responses on four QoL domains (physical health, psychological, social relationships, and environmental) 18-months into the recovery phase of FEP. We then examined the discriminant validity of these subgroups with respect to clinical, cognitive, and functioning features of FEP., Method: Demographic and clinical characteristics, QoL, cognition, and functioning were assessed in 100 people with FEP at the 18-month follow-up of a randomised controlled trial of Individual Placement Support, which aims to facilitate vocational recovery. QoL was measured using the World Health Organisation's QoL-BRIEF. A two-stage clustering approach using Ward's method and Squared Euclidean Distance with a k-means confirmation was conducted. Multinomial logistic regressions were used to establish external validity., Results: Three QoL subgroups emerged: a 'good' subgroup with relatively high QoL across all domains (31%), an 'intermediate' subgroup with relatively low psychological QoL (48%) and a 'poor' subgroup with markedly low social relationship QoL (21%). Negative symptoms, depressive symptoms, social/occupational functioning, and social inclusion at follow-up predicted subgroup membership. Sensitivity analysis found similar results., Conclusion: Although some individuals with FEP have QoL comparable to individuals without mental ill health, QoL can remain concerningly low despite treatment efforts. Future research on interventions that target factors associated with poor QoL, such as low social inclusion, is required to counteract prolonged poor QoL in FEP., (© 2022. The Author(s).)

Background: Environmental disasters such as wildfires, floods and droughts can introduce significant interruptions and trauma to impacted communities. Children and young people can be disproportionately affected with additional educational disruptions. However, evaluating the impact of disasters is challenging due to difficulties in establishing studies and recruitment post-disasters., Objectives: We aimed to (1) develop a Bayesian model using aggregated school-level data to evaluate the impact of environmental disasters on academic achievement and (2) evaluate the impact of the 2014 Hazelwood mine fire (a six-week fire event in Australia)., Methods: Bayesian hierarchical meta-regression was developed to evaluate the impact of the mine fire using easily accessible aggregated school-level data from the standardised National Assessment Program-Literacy and Numeracy (NAPLAN) test. NAPLAN results and school characteristics (2008-2018) from 69 primary/secondary schools with different levels of mine fire-related smoke exposure were used to estimate the impact of the event. Using an interrupted time series design, the model estimated immediate effects and post-interruption trend differences with full Bayesian statistical inference., Results: Major academic interruptions across NAPLAN domains were evident in high exposure schools in the year post-mine fire (greatest interruption in Writing: 11.09 [95%CI: 3.16-18.93], lowest interruption in Reading: 8.34 [95%CI: 1.07-15.51]). The interruption was comparable to a four to a five-month delay in educational attainment and had not fully recovered after several years., Conclusion: Considerable academic delays were found as a result of a mine fire, highlighting the need to provide educational and community-based supports in response to future events. Importantly, this work provides a statistical method using readily available aggregated data to assess the educational impacts in response to other environmental disasters., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright: © 2023 Gao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Fat mass and obesity-associated (FTO) gene is strongly associated with obesity which brings a major health threat. Altered expression of its encoded protein FTO in the hypothalamus has been identified to contribute to central control of appetite and body weight. However, its molecular mechanisms remain elusive., Methods: Mouse hypothalamic POMC cell line N43/5 was treated with FTO inhibitor rhein, FTO shRNA, or extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor U0126 to inhibit FTO or ERK1/2. Rhein and U0126 were injected into lateral ventricle of the mice by intracerebroventricular cannulation. Western blotting and immunofluorescent assays were performed to monitor protein level., Results: This study identified that inhibition of FTO in N43/5 cells led to phosphorylation of signal transducer and activator of transcription 3 (STAT3) at S727 site and induced p-STAT3-S727 nuclear translocation. We further showed that FTO inhibition promoted phosphorylation of ERK1/2; specific inhibition of ERK1/2 signaling by U0126 could abolish the effect of FTO inhibition on STAT3-S727 phosphorylation and nuclear translocation. Furthermore, we found that inhibition of hypothalamic FTO promoted STAT3-S727 phosphorylation in the hypothalamic arcuate nucleus, and the mice showed reductions in food intake and body weight. In addition, inhibition of hypothalamic ERK1/2 could abolish the effects of FTO inhibition on STAT3-S727 phosphorylation, reductions of food intake and body weight., Conclusion: Our in vitro and in vivo data suggest that the inhibition of hypothalamic FTO could activate STAT3 through ERK1/2, which is potentially associated with reductions in food intake and body weight., (© 2022 S. Karger AG, Basel.)

Origin of differently sized respiratory droplets is fundamental for clarifying their viral loads and the sequential transmission mechanism of SARS-CoV-2 in indoor environments. Transient talking activities characterized by low (0.2 L/s), medium (0.9 L/s), and high (1.6 L/s) airflow rates of monosyllabic and successive syllabic vocalizations were investigated by computational fluid dynamics (CFD) simulations based on a real human airway model. SST k-ω model was chosen to predict the airflow field, and the discrete phase model (DPM) was used to calculate the trajectories of droplets within the respiratory tract. The results showed that flow field in the respiratory tract during speech is characterized by a significant laryngeal jet, and bronchi, larynx, and pharynx-larynx junction were main deposition sites for droplets released from the lower respiratory tract or around the vocal cords, and among which, over 90% of droplets over 5 µm released from vocal cords deposited at the larynx and pharynx-larynx junction. Generally, droplets' deposition fraction increased with their size, and the maximum size of droplets that were able to escape into external environment decreased with the airflow rate. This threshold size for droplets released from the vocal folds was 10-20 µm, while that for droplets released from the bronchi was 5-20 µm under various airflow rates. Besides, successive syllables pronounced at low airflow rates promoted the escape of small droplets, but do not significantly affect the droplet threshold diameter. This study indicates that droplets larger than 20 µm may entirely originate from the oral cavity, where viral loads are lower; it provides a reference for evaluating the relative importance of large-droplet spray and airborne transmission route of COVID-19 and other respiratory infections., (© Tsinghua University Press 2023.)

Aims: Services for individuals with a first episode of psychosis or at ultra-high risk of psychosis have become a treatment model of choice in mental health care. The longitudinal changes in clinical and functional outcomes as a result of real-world treatment remain under-reported., Methods: We analysed data from first episode of psychosis and ultra-high risk services delivered across Australian primary youth mental health care services known as headspace between 19 June 2017 and 30 September 2019. Outcome measures were completed and entered into a minimum dataset every 90 days a participant was receiving treatment and included psychiatric symptomatology (Brief Psychiatric Rating Scale and psychological distress, K10) and psychosocial functioning (Social and Occupational Functioning Assessment Scale and My Life Tracker). Linear mixed-effects models were used to evaluate changes in outcome over time., Results: Outcome data from a total of 1252 young people were evaluated (643 first episode of psychosis, 609 ultra-high risk). Of those who entered ultra-high risk services, 11.8% transitioned to first episode of psychosis services. Overall, substantial improvement in clinical (Brief Psychiatric Rating Scale, K10) and functional (Social and Occupational Functioning Assessment Scale, My Life Tracker) outcomes were seen across groups and outcomes. Ultra-high risk patients showed a greater reduction in distress symptoms, while first episode of psychosis patients experienced a greater reduction in positive psychosis symptoms. Although clinical outcomes showed a plateau effect after approximately 3 months of care, improvement in functional outcomes (Social and Occupational Functioning Assessment Scale, My Life Tracker) continued later in treatment., Conclusion: These findings support the use of real-time, real-world and low-cost administrative data to rigorously evaluate symptomatic and functional outcomes in early psychosis treatment settings. Findings that functional outcomes improve past the remittance of clinical outcomes also support the functional recovery focus of early psychosis services and remaining high levels of distress suggest the need for ultra-high risk services to extend beyond 6 months of care.